Surgical management of fibrotic encapsulation of the fluocinolone acetonide implant in CAPN5-associated proliferative vitreoretinopathy.

Science.gov (United States)

Tlucek, Paul S; Folk, James C; Sobol, Warren M; Mahajan, Vinit B

2013-01-01

To review fibrosis of fluocinolone acetonide (FA) implants in subjects with CAPN5 autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV). A retrospective case series was assembled from ADNIV patients in which there was fibrotic encapsulation of a fluocinolone acetonide implant. CAPN5 genotypes and surgical repair techniques were reviewed. Two eyes of two ADNIV patients developed a fibrotic capsule over the fluocinolone acetonide implant. Both patients had Stage IV disease. Patient A had a c.731T > C mutation in the CAPN5 gene and patient B had a c.728G > T mutation. The fibrotic membrane was surgically excised and the implant function was restored. The exuberant fibrotic response in later stages of ADNIV may be resistant to local immunosuppression with steroids. Surgical excision of fibrotic membranes over FA implants can reestablish local steroid delivery in cases of severe proliferative vitreoretinopathy.

Myeloid-Related Protein-14/MRP-14/S100A9/Calgranulin B is Associated with Inflammation in Proliferative Diabetic Retinopathy.

Science.gov (United States)

Abu El-Asrar, Ahmed M; Alam, Kaiser; Siddiquei, Mohammad M; Van den Eynde, Kathleen; Mohammad, Ghulam; De Hertogh, Gert; Opdenakker, Ghislain

2018-01-01

To investigate the expression of the leukocyte proteins myeloid-related protein (MRP)-8 and MRP-14 in proliferative diabetic retinopathy (PDR) and the effect of MRP-8/MRP-14 (calprotectin) heterodimer on induction of proinflammatory factors in human retinal microvascular endothelial cells (HRMEC). Epiretinal membranes from 20 patients with PDR and 10 patients with proliferative vitreoretinopathy (PVR), vitreous fluid samples from PDR and non-diabetic subjects and HRMEC were studied by immunohistochemistry and Western blot analysis. MRP-14 expression was localized in endothelial cells, leukocytes and myofibroblasts in all PDR membranes. MRP-8 expression was limited to intravascular leukocytes in 42% of the studied membranes. In PVR membranes, MRP-14 was expressed in leukocytes and myofibroblasts, whereas MRP-8 immunoreactivity was limited to leukocytes. MRP-14 was significantly upregulated in vitreous from PDR patients. MRP-8/MRP-14 (calprotectin) increased expression of intercellular adhesion molecule-1, but attenuated vascular cell adhesion molecule-1 expression in HRMEC. Increased MRP-14 levels are associated with inflammation in PDR.

Surgical management of fibrotic encapsulation of the fluocinolone acetonide implant in CAPN5-associated proliferative vitreoretinopathy

Directory of Open Access Journals (Sweden)

Tlucek PS

2013-06-01

Full Text Available Paul S Tlucek,1 James C Folk,1 Warren M Sobol,2 Vinit B Mahajan1,3 1Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, IA, USA; 2Retina Physicians and Surgeons, Dayton, OH, USA; 3Omics Laboratory, University of Iowa, Iowa City, IA, USA Objective: To review fibrosis of fluocinolone acetonide (FA implants in subjects with CAPN5 autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV. Methods: A retrospective case series was assembled from ADNIV patients in which there was fibrotic encapsulation of a fluocinolone acetonide implant. CAPN5 genotypes and surgical repair techniques were reviewed. Results: Two eyes of two ADNIV patients developed a fibrotic capsule over the fluocinolone acetonide implant. Both patients had Stage IV disease. Patient A had a c.731T > C mutation in the CAPN5 gene and patient B had a c.728G > T mutation. The fibrotic membrane was surgically excised and the implant function was restored. Conclusion: The exuberant fibrotic response in later stages of ADNIV may be resistant to local immunosuppression with steroids. Surgical excision of fibrotic membranes over FA implants can reestablish local steroid delivery in cases of severe proliferative vitreoretinopathy. Keywords: autosomal dominant neovascular inflammatory vitreoretinopathy, ADNIV, CAPN5, calpain-5, Retisert, fluocinolone acetonide, fibrotic encapsulation

Dealings between Cataract and Retinal Reattachment Surgery in PVR

Directory of Open Access Journals (Sweden)

Svenja Deuchler

2016-01-01

Full Text Available Introduction. To evaluate the impact of the eye lens status and oil side effects on the outcome of vitreoretinal surgery in retinal detachment with proliferative vitreoretinopathy (PVR and a temporary silicone oil tamponade (SOT. Methods. 101 eyes were analyzed retrospectively and 103 eyes prospectively in regard to their retinal reattachment success rate and key factors for the outcome. Subgroup analysis of 27 eyes with Scheimpflug lens photography (SLP before and after retinal reattachment service with SOT was performed. For SLP (65% phakic eyes a Pentacam densitometry reference body with 3 mm diameter was chosen and 3 segments (anterior/mid/posterior were evaluated separately after a quality check. Results. The retinal reattachment rate was highest in the prospective pseudophakic group (p=0.039. Lens transparency loss occurred earlier in middle aged patients than in younger patients. Besides the nucleus, layers posterior and anterior to it showed specific transparency changes. The emulsification rate was higher when eyes had been operated on in the anterior chamber before retinal reattachment service. Conclusions. Retinal reattachment surgery seems to benefit from preoperative cataract removal. We found significant lens changes in the nucleus as well as in the layers anterior and posterior to it. This corresponds to the histology of the lens epithelium published before.

Annexin A2 in Proliferative Vitreoretinopathy

Science.gov (United States)

2016-10-01

normal architecture of the Anxa2+/+ retina with loss of defined cell layers and retraction of the retina to form a mass containing pigmented cells...ectopic presence of RPE cells, and no retraction of the retina. In the Anxa2-/- eye, the normal architecture of the retina and its typical distribution...eyes. For semi-quantitative scoring, we have devised an overall PVR Histology Index ( PHI ) (Figure 2). The PHI is based on the degree of retinal

Annexin A2 in Proliferative Vitreoretinopathy

Science.gov (United States)

2017-10-01

that breaches the blood-retinal barrier, leakage of plasma proteins and circulating blood cells, possibly together with local hypoxia, conspire to...immunofluorescence staining to document the migration of A2-positive cells from the RPE to the surface of the retina in PVR (Fig. 3). We have also detected a few...readily detected (Fig. 9B, 9C). Cells in both groups were also positive for A2. These data indicate that expression of A2 in both RPE cells and

Upregulation of Mir-21 Levels in the Vitreous Humor Is Associated with Development of Proliferative Vitreoretinal Disease.

Directory of Open Access Journals (Sweden)

Ayumi Usui-Ouchi

Full Text Available MicroRNAs (miRNAs are small noncoding RNAs that regulate gene expression by post-transcriptional inhibition of mRNA translation. Dysregulation of miRNAs, including circulating miRNAs, has been reported to play an important role in the development of various diseases, including fibrotic diseases. Aberrant expression of miRNAs in the vitreous humor of vitreoretinal diseased eyes has been reported. However, the expression pattern of miRNAs present in the vitreous humor of proliferative vitreoretinal disease (PVD patients, including proliferative diabetic retinopathy (PDR, and proliferative vitreoretinopathy (PVR, remains unknown. To investigate the factors important for the development of PVD, we characterized the miRNAs present in the vitreous humor of PVD patients and analyzed the expression profiles of 377 miRNAs using quantitative polymerase chain reaction-based miRNA arrays. The expression of a specific subset of miRNAs, previously reported to be associated with the development of angiogenesis and fibrosis, was significantly altered in the vitreous of PVD patients. Among these miRNAs, we identified miR-21 as a candidate fibrotic miRNA with an important role in the pathogenesis of PVD. Increased miR-21 levels in the vitreous were associated with retinal fibrosis, including PVR and PDR. Because epithelial-mesenchymal transition (EMT of retinal pigment epithelial cells (RPECs plays a critical role in retinal fibrosis, the expression of miR-21 in human RPECs was determined. Its expression in RPECs was induced by transforming growth factor-β, a key growth factor involved in fibrogenesis, and was enhanced by high glucose culture conditions, suggesting that miR-21 expression positively correlates with disease progression. Gain- and loss-of-function studies revealed that miR-21 promoted cell proliferation and migration of ARPE-19 cells without affecting EMT-related gene expression. Together, our studies have identified miR-21 as a potential disease

Calcium-independent phospholipase A2 regulates retinal pigment epithelium proliferation and may be important in the pathogenesis of retinal diseases

DEFF Research Database (Denmark)

Kolko, M; Kiilgaard, J F; Wang, J

2009-01-01

Calcium-independent phospholipase A2, group VIA (iPLA2-VIA) is involved in cell proliferation. This study aimed to evaluate the role of iPLA2-VIA in retinal pigment epithelium (RPE) cell proliferation and in retinal diseases involving RPE proliferation. A human RPE cell line (ARPE-19) was used...... the expression of iPLA2-VIA in proliferative vitreoretinopathy (PVR). PVR membranes revealed nuclear expression of iPLA2-VIA in the RPE cells which had migrated and participated in the formation of the membranes. Overall, the present results point to an important role of iPLA2-VIA in the regulation of RPE...

Fine Mapping of the Dominant Potyvirus Resistance Gene Pvr7 Reveals a Relationship with Pvr4 in Capsicum annuum.

Science.gov (United States)

Venkatesh, Jelli; An, Jeongtak; Kang, Won-Hee; Jahn, Molly; Kang, Byoung-Cheorl

2018-01-01

Pepper mottle virus (PepMoV) is the most common potyvirus infection of pepper plants and causes significant yield losses. The Pvr7 gene from Capsicum chinense PI159236 and the Pvr4 gene from C. annuum CM334 both have been reported to confer dominant resistance to PepMoV. The Pvr7 locus conferring resistance to PepMoV in C. annuum '9093' was previously mapped to chromosome 10. To develop a high-resolution map of the Pvr7 locus in 9093, we constructed an intraspecific F 2 mapping population consisting of 916 individuals by crossing PepMoV-resistant C. annuum '9093' and the PepMoV-susceptible C. annuum 'Jeju'. To delimit the Pvr7 target region, single-nucleotide polymorphism (SNP) markers derived from the Pvr4 region were used for genotyping the F 2 population. Molecular mapping delimited the Pvr7 locus to a physical interval of 258 kb, which was the same region as Pvr4 on chromosome 10. Three SNP markers derived from Pvr4 mapping perfectly cosegregated with PepMoV resistance. Sequencing analyses of the Pvr7 flanking markers and the Pvr4-specific gene indicated that Pvr7 and Pvr4 are the same gene. Resistance spectrum analysis of 9093 against pepper potyviruses showed that 9093 has a resistance spectrum similar to that of cultivar CM334. These combined results demonstrate that, unlike previously thought, the dominant PepMoV resistance in 9093 could be derived from C. annuum 'CM334', and that Pvr4 and Pvr7 should be considered as the same locus.

Resveratrol inhibits transforming growth factor-β2-induced epithelial-to-mesenchymal transition in human retinal pigment epithelial cells by suppressing the Smad pathway

Directory of Open Access Journals (Sweden)

Chen CL

2017-01-01

Full Text Available Ching-Long Chen,1,2 Yi-Hao Chen,1,2 Ming-Cheng Tai,2 Chang-Min Liang,2 Da-Wen Lu,1,2 Jiann-Torng Chen1,2 1Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan; 2Department of Ophthalmology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan Abstract: Proliferative vitreoretinopathy (PVR is the main cause of failure following retinal detachment surgery. Transforming growth factor (TGF-β2-induced epithelial-to-mesenchymal transition (EMT plays an important role in the development of PVR, and EMT inhibition decreases collagen gel contraction and fibrotic membrane formation, resulting in prevention of PVR. Resveratrol is naturally found in red wine and has inhibitory effects on EMT. Resveratrol is widely used in cardioprotection, neuroprotection, chemotherapy, and antiaging therapy. The purpose of this study was to investigate the effects of resveratrol on TGF-β2-induced EMT in ARPE-19 cells in vitro. We found that resveratrol suppressed the decrease of zona occludens-1 (ZO-1 and caused an increase of alpha-smooth muscle actin expression in TGF-β2-treated ARPE-19 cells, assessed using Western blots; moreover, it also suppressed the decrease in ZO-1 and the increase of vimentin expression, observed using immunocytochemistry. Resveratrol attenuated TGF-β2-induced wound closure and cell migration in ARPE-19 cells in a scratch wound test and modified Boyden chamber assay, respectively. We also found that resveratrol reduced collagen gel contraction – assessed by collagen matrix contraction assay – and suppressed the phosphorylation of Smad2 and Smad3 in TGF-β2-treated ARPE-19 cells. These results suggest that resveratrol mediates anti-EMT effects, which could be used in the prevention of PVR. Keywords: resveratrol, epithelial-to-mesenchymal transition, proliferative vitreoretinopathy, transforming growth factor-β2, retinal pigment epithelial cells

PDGF stimulation of Mueller cell proliferation: Contributions of c-JNK and the PI3K/Akt pathway

International Nuclear Information System (INIS)

Moon, Sang Woong; Chung, Eun Jee; Jung, Sun-Ah; Lee, Joon H.

2009-01-01

Platelet-derived growth factor (PDGF) has a critical role in proliferative vitreoretinopathy (PVR) as a chemoattractant and mitogen for retinal pigment epithelial cells and retinal glial cells. Here, we investigated the potential effects of PDGF on the proliferation of Mueller cells and the intracellular signaling pathway mediating these changes. PDGF induced Mueller cell proliferation and increased phosphorylation of the PDGF receptor (PDGFR), as shown by an MTT assay and immunoprecipitation analyses. Both effects were blocked by JNJ, a PDGFR-selective tyrosine kinase inhibitor. PDGF also stimulated phosphorylation of c-JNK and Akt. PDGF-induced Mueller cell proliferation was significantly reduced by pre-treatment with SP600125 and LY294002, inhibitors of c-JNK and Akt phosphorylation, respectively. Our findings collectively indicate that PDGF-stimulated Mueller cell proliferation occurs via activation of the c-JNK and PI3K/Akt signaling pathways. These data provide useful information in establishing the role of Mueller cells in the development of proliferative vitreoretinopathy.

Surgical management of fibrotic encapsulation of the fluocinolone acetonide implant in CAPN5-associated proliferative vitreoretinopathy

OpenAIRE

Tlucek, Paul S; Folk, James C; Sobol, Warren M; Mahajan, Vinit B

2013-01-01

Paul S Tlucek,1 James C Folk,1 Warren M Sobol,2 Vinit B Mahajan1,3 1Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, IA, USA; 2Retina Physicians and Surgeons, Dayton, OH, USA; 3Omics Laboratory, University of Iowa, Iowa City, IA, USA Objective: To review fibrosis of fluocinolone acetonide (FA) implants in subjects with CAPN5 autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV). Methods: A retrospective case series was assembled from ADNIV patie...

Role of macrophage migration inhibitory factor (MIF) in the effects of oxidative stress on human retinal pigment epithelial cells.

Science.gov (United States)

Ko, Ji-Ae; Sotani, Yasuyuki; Ibrahim, Diah Gemala; Kiuchi, Yoshiaki

2017-10-01

Proliferative vitreoretinopathy (PVR) is the major cause of treatment failure in individuals who undergo surgery for retinal detachment. The epithelial-mesenchymal transition (EMT) in retinal pigment epithelium (RPE) cells contributes to the pathogenesis of PVR. Oxidative stress is thought to play a role in the progression of retinal diseases including PVR. We have now examined the effects of oxidative stress on the EMT and related processes in the human RPE cell line. We found that H 2 O 2 induced the contraction of RPE cells in a three-dimensional collagen gel. Analysis of a cytokine array revealed that H 2 O 2 specifically increased the release of macrophage migration inhibitory factor (MIF) from RPE cells. Reverse transcription-polymerase chain reaction and immunoblot analyses showed that H 2 O 2 increased the expression of MIF in RPE cells. Immunoblot and immunofluorescence analyses revealed that H 2 O 2 upregulated the expression of α-SMA and vimentin and downregulated that of ZO-1 and N-cadherin. Consistent with these observations, the transepithelial electrical resistance of cell was reduced by exposure to H 2 O 2 . The effects of oxidative stress on EMT-related and junctional protein expression as well as on transepithelial electrical resistance were inhibited by antibodies to MIF, but they were not mimicked by treatment with recombinant MIF. Finally, analysis with a profiling array for mitogen-activated protein kinase signalling revealed that H 2 O 2 specifically induced the phosphorylation of p38 mitogen-activated protein kinase. Our results thus suggest that MIF may play a role in induction of the EMT and related processes by oxidative stress in RPE cells and that it might thereby contribute to the pathogenesis of PVR. Proliferative vitreoretinopathy is a major complication of rhegmatogenous retinal detachment, and both oxidative stress and induction of the EMT in RPE cells are thought to contribute to the pathogenesis of this condition. We have now

Familial Exudative Vitreoretinopathy.

Science.gov (United States)

Sızmaz, Selçuk; Yonekawa, Yoshihiro; T Trese, Michael

2015-08-01

Familial exudative vitreoretinopathy (FEVR) is a hereditary disease associated with visual loss, particularly in the pediatric group. Mutations in the NDP, FZD4, LRP5, and TSPAN12 genes have been shown to contribute to FEVR. FEVR has been reported to have X-linked recessive, autosomal dominant, and autosomal recessive inheritances. However, both the genotypic and phenotypic features are variable. Novel mutations contributing to the disease have been reported. The earliest and the most prominent finding of the disease is avascularity in the peripheral retina. As the disease progresses, retinal neovascularization, subretinal exudation, partial and total retinal detachment may occur, which may be associated with certain mutations. With early diagnosis and prompt management visual loss can be prevented with laser photocoagulation and anti-VEGF injections. In case of retinal detachment, pars plana vitrectomy alone or combined with scleral buckling should be considered. Identifying asymptomatic family members with various degrees of insidious findings is of certain importance. Wide-field imaging with fluorescein angiography is crucial in the management of this disease. The differential diagnosis includes other pediatric vitreoretinopathies such as Norrie disease, retinopathy of prematurity, and Coats' disease.

Familial Exudative Vitreoretinopathy

Directory of Open Access Journals (Sweden)

Selçuk Sızmaz

2015-08-01

Full Text Available Familial exudative vitreoretinopathy (FEVR is a hereditary disease associated with visual loss, particularly in the pediatric group. Mutations in the NDP, FZD4, LRP5, and TSPAN12 genes have been shown to contribute to FEVR. FEVR has been reported to have X-linked recessive, autosomal dominant, and autosomal recessive inheritances. However, both the genotypic and phenotypic features are variable. Novel mutations contributing to the disease have been reported. The earliest and the most prominent finding of the disease is avascularity in the peripheral retina. As the disease progresses, retinal neovascularization, subretinal exudation, partial and total retinal detachment may occur, which may be associated with certain mutations. With early diagnosis and prompt management visual loss can be prevented with laser photocoagulation and anti-VEGF injections. In case of retinal detachment, pars plana vitrectomy alone or combined with scleral buckling should be considered. Identifying asymptomatic family members with various degrees of insidious findings is of certain importance. Wide-field imaging with fluorescein angiography is crucial in the management of this disease. The differential diagnosis includes other pediatric vitreoretinopathies such as Norrie disease, retinopathy of prematurity, and Coats’ disease. (Turk J Ophthalmol 2015; 45: 164-168

Functional characterization of rs2229094 (T>C polymorphism in the tumor necrosis factor locus and lymphotoxin alpha expression in human retina: the Retina 4 project

Directory of Open Access Journals (Sweden)

Pastor-Idoate S

2017-05-01

Full Text Available Salvador Pastor-Idoate,1,2 Irene Rodríguez-Hernández,2,3 Jimena Rojas,1 Lucia Gonzalez-Buendia,1 Santiago Delgado-Tirado,1,4 Jose Carlos López,1 Rogelio González-Sarmiento,2,3 Jose C Pastor1,4 1IOBA Eye Institute, University of Valladolid, Valladolid, 2Molecular Medicine Unit, Department of Medicine, 3Molecular and Cellular Cancer Biology Institute, High Council of Scientific Research, Biomedical Research Institute of Salamanca, University of Salamanca, Salamanca, 4Department of Ophthalmology, Hospital Clínico Universitario, Valladolid, Spain Purpose: The objective of this study is to determine the expression and localization of lymphotoxin alpha (LTA in human retinas and the functionality of one of its polymorphisms rs2229094 (C13R (T>C, previously associated with proliferative vitreoretinopathy (PVR development.Materials and methods: Total RNA from three healthy human retinas were extracted and subjected to reverse transcription-polymerase chain reaction (RT-PCR analysis, using flanking primers of LTA cDNA. In addition, three human eyes with retinal detachment (RD and three healthy control eyes were subjected to immunohistochemistry (IHC with a specific antibody against LTA. The functionality of T and C alleles was assessed by using pCEFL-Flag expression vector and transient transfection assays in COS-1 cell line. In addition, expression analysis by RT-PCR, Western blot and subcellular localization of both alleles and by immunofluorescence assay was performed.Results: RT-PCR analysis revealed no significant levels of messenger RNA (mRNA LTA in healthy human retinas. Sequential IHC staining showed differences between healthy human and RD retinas. No differences in mRNA and protein expression levels and in subcellular localization between both alleles were found. Both alleles were located in the cytoplasm of COS-1 cells.Conclusion: Although results suggest lack of functionality, the differences found in IHC study and its strong association

PVR/CD155 Ala67Thr Mutation and Cleft Lip/Palate.

Science.gov (United States)

Vieira, Alexandre R; Letra, Ariadne; Silva, Renato M; Granjeiro, Jose M; Shimizu, Takehiko; Poletta, Fernando A; Mereb, Juan C; Castilla, Eduardo E; Orioli, Iêda M

2018-03-01

The 19q13 locus has been linked to cleft lip and palate by our group and independently by others. Here we fine mapped the region in an attempt to identify an etiological variant that can explain cleft lip and palate occurrence. A total of 2739 individuals born with cleft lip and palate, related to individuals born with cleft lip and palate, and unrelated were studied. We used linkage and association approaches to fine map the interval between D19S714 and D19S433 and genotypes were defined by the use of TaqMan chemistry. We confirmed our previous findings that markers in PVR/CD155 are associated with cleft lip and palate. We studied the mutation Ala67Thr further and calculated its penetrance. We also attempted to detect PVR/CD155 expression in human whole saliva. Our results showed that markers in PVR/CD155 are associated with cleft lip and palate and the penetrance of the Ala67Thr is very low (between 1% and 5%). We could not detect PVR/CD155 expression in adult human whole saliva and PVR/CD155 possibly interacts with maternal infection to predispose children to cleft lip only.

Comparison of four surgical techniques for management of pseudophakic and aphakic retinal detachment: a multicenter clinical trial.

Science.gov (United States)

Moradian, Siamak; Ahmadieh, Hamid; Faghihi, Hooshang; Ramezani, Alireza; Entezari, Morteza; Banaee, Touka; Heidari, Ebadollah; Behboudi, Hassan; Yasseri, Mehdi

2016-09-01

To compare the visual and anatomical outcomes of four surgical techniques to manage pseudophakic and aphakic retinal detachment (PARD). In a multicenter randomized clinical trial, 211 eyes of 211 patients with PARD and proliferative vitreoretinopathy (PVR) grade B or less were randomly assigned to one of the four treatment groups: (1) scleral buckling (SB), 50 eyes, (2) vitrectomy without band, 51 eyes, (3) vitrectomy with encircling band (EB), 58 eyes, and (4) triamcinolone acetonide (TA) assisted vitrectomy, 52 eyes. Patients were followed for 12 months after the surgery. The best-corrected visual acuity (BCVA) and retinal reattachment rate at each follow-up time point were considered as the primary outcome measures. PVR, macular pucker, and cystoid macular edema were considered as the secondary outcomes. Visual improvement was achieved in all treatment groups relative to the baseline at all time points (all Ps  0.99). There were no statistically significant differences among the groups in terms of adverse events. SB, TA-assisted vitrectomy, and vitrectomy with and without buckle had comparable outcomes in the management of PARD.

Lycopene inhibits PDGF-BB-induced retinal pigment epithelial cell migration by suppression of PI3K/Akt and MAPK pathways

Energy Technology Data Exchange (ETDEWEB)

Chan, Chi-Ming [School of Medicine, Fu Jen Catholic University, Taipei Hsien, Taiwan, ROC (China); Department of Ophthalmology, Cardinal Tien Hospital, Taipei Hsien, Taiwan, ROC (China); Fang, Jia-You [Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, Kweishan, Taoyuan, Taiwan, ROC (China); Lin, Hsin-Huang [School of Medicine, Fu Jen Catholic University, Taipei Hsien, Taiwan, ROC (China); Yang, Chi-Yea [Department of Biotechnology, Vanung University, Taoyuan, Taiwan, ROC (China); Hung, Chi-Feng, E-mail: 054317@mail.fju.edu.tw [School of Medicine, Fu Jen Catholic University, Taipei Hsien, Taiwan, ROC (China)

2009-10-09

Retinal pigment epithelial (RPE) cells play a dominant role in the development of proliferative vitreoretinopathy (PVR), which is the leading cause of failure in retinal reattachment surgery. Several studies have shown that platelet-derived growth factor (PDGF) exhibits chemotaxis and proliferation effects on RPE cells in PVR. In this study, the inhibitory effect of lycopene on PDGF-BB-induced ARPE19 cell migration is examined. In electric cell-substrate impedance sensing (ECIS) and Transwell migration assays, significant suppression of PDGF-BB-induced ARPE19 cell migration by lycopene is observed. Cell viability assays show no cytotoxicity of lycopene on RPE cells. Lycopene shows no effect on ARPE19 cell adhesion and is found to inhibit PDGF-BB-induced tyrosine phosphorylation and the underlying signaling pathways of PI3K, Akt, ERK and p38 activation. However, PDGF-BB and lycopene show no effects on JNK activation. Taken together, our results demonstrate that lycopene inhibits PDGF-BB-induced ARPE19 cell migration through inhibition of PI3K/Akt, ERK and p38 activation.

Lycopene inhibits PDGF-BB-induced retinal pigment epithelial cell migration by suppression of PI3K/Akt and MAPK pathways

International Nuclear Information System (INIS)

Chan, Chi-Ming; Fang, Jia-You; Lin, Hsin-Huang; Yang, Chi-Yea; Hung, Chi-Feng

2009-01-01

Retinal pigment epithelial (RPE) cells play a dominant role in the development of proliferative vitreoretinopathy (PVR), which is the leading cause of failure in retinal reattachment surgery. Several studies have shown that platelet-derived growth factor (PDGF) exhibits chemotaxis and proliferation effects on RPE cells in PVR. In this study, the inhibitory effect of lycopene on PDGF-BB-induced ARPE19 cell migration is examined. In electric cell-substrate impedance sensing (ECIS) and Transwell migration assays, significant suppression of PDGF-BB-induced ARPE19 cell migration by lycopene is observed. Cell viability assays show no cytotoxicity of lycopene on RPE cells. Lycopene shows no effect on ARPE19 cell adhesion and is found to inhibit PDGF-BB-induced tyrosine phosphorylation and the underlying signaling pathways of PI3K, Akt, ERK and p38 activation. However, PDGF-BB and lycopene show no effects on JNK activation. Taken together, our results demonstrate that lycopene inhibits PDGF-BB-induced ARPE19 cell migration through inhibition of PI3K/Akt, ERK and p38 activation.

Interleukin and growth factor levels in subretinal fluid in rhegmatogenous retinal detachment: a case-control study.

Directory of Open Access Journals (Sweden)

Lukas J A G Ricker

Full Text Available BACKGROUND: Rhegmatogenous retinal detachment (RRD is a major cause of visual loss in developed countries. Proliferative vitreoretinopathy (PVR, an eye-sight threatening complication of RRD surgery, resembles a wound-healing process with inflammation, scar tissue formation, and membrane contraction. This study was performed to determine the possible involvement of a wide range of cytokines in the future development of PVR, and to identify predictors of PVR and visual outcome. METHODOLOGY: A multiplex immunoassay was used for the simultaneous detection of 29 different cytokines in subretinal fluid samples from patients with primary RRD. Of 306 samples that were collected and stored in our BioBank between 2001 and 2008, 21 samples from patients who developed postoperative PVR were compared with 54 age-, sex-, and storage-time-matched RRD control patients who had an uncomplicated postoperative course during the overall follow-up period. FINDINGS: Levels of IL-1α, IL-2, IL-3, IL-6, VEGF, and ICAM-1 were significantly higher (P0.05. Multivariate logistic regression analysis revealed that IL-3 (P = 0.001, IL-6 (P = 0.047, ICAM-1 (P = 0.010, and preoperative visual acuity (P = 0.026 were independent predictors of postoperative PVR. Linear regression analysis showed that ICAM-1 (P = 0.005 and preoperative logMAR visual acuity (P = 0.001 were predictive of final visual outcome after primary RRD repair. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that after RRD onset an exaggerated response of certain cytokines may predispose to PVR. Sampling at a time close to the onset of primary RRD may thus provide clues as to which biological events may initiate the development of PVR and, most importantly, may provide a means for therapeutic control.

Visusminderung unter Silikon

DEFF Research Database (Denmark)

Dornonville de la Cour, Morten; Lux, Anja; Heegaard, Steffen

2010-01-01

Silicone oil is used as intravitreal tamponading agent in surgery for rhegmatogenous retinal detachment (RRD) cases complicated with proliferative vitreoretinopathy (PVR). Recently, a number of case series have appeared where profound central visual loss has been found in eyes after uncomplicated...... vitrectomy with silicone tamponade for RRD in eyes with seemingly good visual potential. Several reports have demonstrated the migration of silicone oil droplets into the retina and the optic nerve, others the widespread loss of myelinated optic nerve fibres. These reports are reviewed, and it is concluded...... that caution is warranted when silicone oil is used in eyes with good visual potential. Finally the additional danger of central visual loss should be taken into consideration when deciding to use silicone oil or gas as intravitreal tamponade....

Genetics Home Reference: familial exudative vitreoretinopathy

Science.gov (United States)

... A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. ... Resources (2 links) GeneReview: Familial Exudative Vitreoretinopathy, Autosomal Dominant GeneReview: NDP-Related Retinopathies General Information from MedlinePlus ( ...

Thrombin induces epithelial-mesenchymal transition and collagen production by retinal pigment epithelial cells via autocrine PDGF-receptor signaling.

Science.gov (United States)

Bastiaans, Jeroen; van Meurs, Jan C; van Holten-Neelen, Conny; Nagtzaam, Nicole M A; van Hagen, P Martin; Chambers, Rachel C; Hooijkaas, Herbert; Dik, Willem A

2013-12-19

De-differentiation of RPE cells into mesenchymal cells (epithelial-mesenchymal transition; EMT) and associated collagen production contributes to development of proliferative vitreoretinopathy (PVR). In patients with PVR, intraocular coagulation cascade activation occurs and may play an important initiating role. Therefore, we examined the effect of the coagulation proteins factor Xa and thrombin on EMT and collagen production by RPE cells. Retinal pigment epithelial cells were stimulated with factor Xa or thrombin and the effect on zonula occludens (ZO)-1, α-smooth muscle actin (α-SMA), collagen, and platelet-derived growth factor (PDGF)-B were determined by real-time quantitative-polymerase chain reaction (RQ-PCR), immunofluorescence microscopy, and HPLC and ELISA for collagen and PDGF-BB in culture supernatants, respectively. PDGF-receptor activation was determined by phosphorylation analysis and inhibition studies using the PDGF-receptor tyrosine kinase inhibitor AG1296. Thrombin reduced ZO-1 gene expression (P production of α-SMA and collagen increased. In contrast to thrombin, factor Xa hardly stimulated EMT by RPE. Thrombin clearly induced PDGF-BB production and PDGF-Rβ chain phosphorylation in RPE. Moreover, AG1296 significantly blocked the effect of thrombin on EMT and collagen production. Our findings demonstrate that thrombin is a potent inducer of EMT by RPE via autocrine activation of PDGF-receptor signaling. Coagulation cascade-induced EMT of RPE may thus contribute to the formation of fibrotic retinal membranes in PVR and should be considered as treatment target in PVR.

The Clustered, Regularly Interspaced, Short Palindromic Repeats-associated Endonuclease 9 (CRISPR/Cas9)-created MDM2 T309G Mutation Enhances Vitreous-induced Expression of MDM2 and Proliferation and Survival of Cells.

Science.gov (United States)

Duan, Yajian; Ma, Gaoen; Huang, Xionggao; D'Amore, Patricia A; Zhang, Feng; Lei, Hetian

2016-07-29

The G309 allele of SNPs in the mouse double minute (MDM2) promoter locus is associated with a higher risk of cancer and proliferative vitreoretinopathy (PVR), but whether SNP G309 contributes to the pathogenesis of PVR is to date unknown. The clustered regularly interspaced short palindromic repeats (CRISPR)-associated endonuclease (Cas) 9 from Streptococcus pyogenes (SpCas9) can be harnessed to manipulate a single or multiple nucleotides in mammalian cells. Here we delivered SpCas9 and guide RNAs using dual adeno-associated virus-derived vectors to target the MDM2 genomic locus together with a homologous repair template for creating the mutation of MDM2 T309G in human primary retinal pigment epithelial (hPRPE) cells whose genotype is MDM2 T309T. The next-generation sequencing results indicated that there was 42.51% MDM2 G309 in the edited hPRPE cells using adeno-associated viral CRISPR/Cas9. Our data showed that vitreous induced an increase in MDM2 and subsequent attenuation of p53 expression in MDM2 T309G hPRPE cells. Furthermore, our experimental results demonstrated that MDM2 T309G in hPRPE cells enhanced vitreous-induced cell proliferation and survival, suggesting that this SNP contributes to the pathogenesis of PVR. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Lutein Inhibits the Migration of Retinal Pigment Epithelial Cells via Cytosolic and Mitochondrial Akt Pathways (Lutein Inhibits RPE Cells Migration

Directory of Open Access Journals (Sweden)

Ching-Chieh Su

2014-08-01

Full Text Available During the course of proliferative vitreoretinopathy (PVR, the retinal pigment epithelium (RPE cells will de-differentiate, proliferate, and migrate onto the surfaces of the sensory retina. Several studies have shown that platelet-derived growth factor (PDGF can induce migration of RPE cells via an Akt-related pathway. In this study, the effect of lutein on PDGF-BB-induced RPE cells migration was examined using transwell migration assays and Western blot analyses. We found that both phosphorylation of Akt and mitochondrial translocation of Akt in RPE cells induced by PDGF-BB stimulation were suppressed by lutein. Furthermore, the increased migration observed in RPE cells with overexpressed mitochondrial Akt could also be suppressed by lutein. Our results demonstrate that lutein can inhibit PDGF-BB induced RPE cells migration through the inhibition of both cytoplasmic and mitochondrial Akt activation.

Long Non-Coding RNA MALAT1 Mediates Transforming Growth Factor Beta1-Induced Epithelial-Mesenchymal Transition of Retinal Pigment Epithelial Cells.

Directory of Open Access Journals (Sweden)

Shuai Yang

Full Text Available To study the role of long non-coding RNA (lncRNA MALAT1 in transforming growth factor beta 1 (TGF-β1-induced epithelial-mesenchymal transition (EMT of retinal pigment epithelial (RPE cells.ARPE-19 cells were cultured and exposed to TGF-β1. The EMT of APRE-19 cells is confirmed by morphological change, as well as the increased expression of alpha-smooth muscle actin (αSMA and fibronectin, and the down-regulation of E-cadherin and Zona occludin-1(ZO-1 at both mRNA and protein levels. The expression of lncRNA MALAT1 in RPE cells were detected by quantitative real-time PCR. Knockdown of MALAT1 was achieved by transfecting a small interfering RNA (SiRNA. The effect of inhibition of MALAT1 on EMT, migration, proliferation, and TGFβ signalings were observed. MALAT1 expression was also detected in primary RPE cells incubated with proliferative vitreoretinopathy (PVR vitreous samples.The expression of MALAT1 is significantly increased in RPE cells incubated with TGFβ1. MALAT1 silencing attenuates TGFβ1-induced EMT, migration, and proliferation of RPE cells, at least partially through activating Smad2/3 signaling. MALAT1 is also significantly increased in primary RPE cells incubated with PVR vitreous samples.LncRNA MALAT1 is involved in TGFβ1-induced EMT of human RPE cells and provides new understandings for the pathogenesis of PVR.

Surgical Management of Traumatic Retinal Detachment with Primary Vitrectomy in Adult Patients

Directory of Open Access Journals (Sweden)

Katarzyna Nowomiejska

2017-01-01

Full Text Available Purpose. To evaluate functional and anatomical results of pars plana vitrectomy (PPV in the retinal detachment (RD followed by severe eye trauma. Methods. Retrospective analysis of medical records of forty-one consecutive patients treated with 23-gauge PPV due to traumatic RD. Age, gender, timing of PPV, visual acuity, and presence of intraocular foreign body (IOFB and proliferative vitreoretinopathy (PVR were included in the analysis. Results. Mean age of patients was 47 years; the majority of patients were men (88%. Closed globe injury was present in 21 eyes and open globe injury in 20 eyes (IOFB in 13 eyes, penetration injury in 4 eyes, and eye rupture in 3 eyes. Mean follow-up period was 14 months; mean timing of PPV was 67 days. Twenty-seven (66% eyes had a functional success; 32 eyes (78% had anatomical success. As a tamponade silicone oil was used in 33 cases and SF6 gas in 8 cases. Conclusions. Severe eye injuries are potentially devastating for vision, but vitreoretinal surgery can improve anatomical and functional outcomes. Among analysed pre- and intra- and postoperative factors, absence of PVR, postoperative retinal attachment, and silicone oil as a tamponade were related to significantly improved visual acuity.

PVR: Patch-to-Volume Reconstruction for Large Area Motion Correction of Fetal MRI.

Science.gov (United States)

Alansary, Amir; Rajchl, Martin; McDonagh, Steven G; Murgasova, Maria; Damodaram, Mellisa; Lloyd, David F A; Davidson, Alice; Rutherford, Mary; Hajnal, Joseph V; Rueckert, Daniel; Kainz, Bernhard

2017-10-01

In this paper, we present a novel method for the correction of motion artifacts that are present in fetal magnetic resonance imaging (MRI) scans of the whole uterus. Contrary to current slice-to-volume registration (SVR) methods, requiring an inflexible anatomical enclosure of a single investigated organ, the proposed patch-to-volume reconstruction (PVR) approach is able to reconstruct a large field of view of non-rigidly deforming structures. It relaxes rigid motion assumptions by introducing a specific amount of redundant information that is exploited with parallelized patchwise optimization, super-resolution, and automatic outlier rejection. We further describe and provide an efficient parallel implementation of PVR allowing its execution within reasonable time on commercially available graphics processing units, enabling its use in the clinical practice. We evaluate PVR's computational overhead compared with standard methods and observe improved reconstruction accuracy in the presence of affine motion artifacts compared with conventional SVR in synthetic experiments. Furthermore, we have evaluated our method qualitatively and quantitatively on real fetal MRI data subject to maternal breathing and sudden fetal movements. We evaluate peak-signal-to-noise ratio, structural similarity index, and cross correlation with respect to the originally acquired data and provide a method for visual inspection of reconstruction uncertainty. We further evaluate the distance error for selected anatomical landmarks in the fetal head, as well as calculating the mean and maximum displacements resulting from automatic non-rigid registration to a motion-free ground truth image. These experiments demonstrate a successful application of PVR motion compensation to the whole fetal body, uterus, and placenta.

Suppressive effect of AMP-activated protein kinase on the epithelial-mesenchymal transition in retinal pigment epithelial cells.

Directory of Open Access Journals (Sweden)

Ryo Matoba

Full Text Available The epithelial-mesenchymal transition (EMT in retinal pigment epithelial (RPE cells plays a central role in the development of proliferative vitreoretinopathy (PVR. The purpose of this study was to investigate the effect of AMP-activated protein kinase (AMPK, a key regulator of energy homeostasis, on the EMT in RPE cells. In this study, EMT-associated formation of cellular aggregates was induced by co-stimulation of cultured ARPE-19 cells with tumor necrosis factor (TNF-α (10 ng/ml and transforming growth factor (TGF-β2 (5 ng/ml. 5-Aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR, a potent activator of AMPK, significantly suppressed TNF-α and TGF-β2-induced cellular aggregate formation (p < 0.01. Dipyridamole almost completely reversed the suppressive effect of AICAR, whereas 5'-amino-5'-deoxyadenosine restored aggregate formation by approximately 50%. AICAR suppressed the downregulation of E-cadherin and the upregulation of fibronectin and α-smooth muscle actin by TNF-α and TGF-β2. The levels of matrix metalloproteinase (MMP-2, MMP-9, interleukin-6, and vascular endothelial growth factor were significantly decreased by AICAR. Activation of the mitogen-activated protein kinase and mammalian target of rapamycin pathways, but not the Smad pathway, was inhibited by AICAR. These findings indicate that AICAR suppresses the EMT in RPE cells at least partially via activation of AMPK. AMPK is a potential target molecule for the prevention and treatment of PVR, so AICAR may be a promising candidate for PVR therapy.

X linked exudative vitreoretinopathy: clinical features and genetic linkage analysis.

Science.gov (United States)

Fullwood, P; Jones, J; Bundey, S; Dudgeon, J; Fielder, A R; Kilpatrick, M W

1993-03-01

A four generation family in which familial exudative vitreoretinopathy is inherited as an X linked condition is described. Essentially the condition is one of abnormal vascularisation and signs at birth are those of a retinopathy superficially resembling retinopathy of prematurity, retinal folds, or, in advanced cases, enophthalmos or even phthisis. Prognosis depends on the progression of the retinal changes. The family members, including seven affected males and five obligate carrier females, have been types for 20 DNA markers, and linkage analysis suggests a gene locus either at Xq21.3 or at Xp11. As the latter region includes the locus for the gene for Norrie disease, it is possible that this and X linked vitreoretinopathy are allelic. We can further speculate that the differences in severity of the clinical manifestations are dependent only upon the timing of the insult.

Retinal detachment repair and cataract surgery in patients with atopic dermatitis.

Science.gov (United States)

Gnana Jothi, V; McGimpsey, S; Sharkey, J A; Chan, W C

2017-09-01

PurposeThe aim of this study is to report a case series of ocular complications including retinal detachment (RD) and cataract in atopic dermatitis (AD) and surgical management involving a majority of Caucasian patients.Patients and methodsThis study is an observational case series, originally designed as an audit. It involves detailed discussion of history, clinical features, and surgical management of patients presenting with retinal detachment and cataracts secondary to severe AD. Six consecutive patients with diagnosis of severe AD requiring posterior segment and cataract surgery were included in the study.ResultsEight eyes of six patients had retinal detachment. Most of them involved the temporal retina. The retinal breaks were located anteriorly close to the ora serrata in six eyes and Giant tear retinal (GRT) detachment was found in two eyes. Five eyes had proliferative vitreo-retinopathy (PVR) at presentation. All six patients had bilateral cataracts and cataract surgery was performed in eleven eyes. Bilateral simultaneous surgery was essential in two patients. Three eyes had secondary intra-ocular lens (IOL) implantation with pars plana vitrectomy for subluxed lens implant.ConclusionsAnterior retinal breaks and temporal RD are common in retinal detachment secondary to AD. PVR is often present, which makes surgical management difficult. Cataract formation is quite often and late subluxation of IOL may occur.

PVR system design of advanced video navigation reinforced with audible sound

NARCIS (Netherlands)

Eerenberg, O.; Aarts, R.; De With, P.N.

2014-01-01

This paper presents an advanced video navigation concept for Personal Video Recording (PVR), based on jointly using the primary image and a Picture-in-Picture (PiP) image, featuring combined rendering of normal-play video fragments with audio and fast-search video. The hindering loss of audio during

Clinical features and prognosis of eyeball rupture: eye injury vitrectomy study.

Science.gov (United States)

Feng, Kang; Wang, Chang-guan; Hu, Yun-tao; Yao, Yi; Jiang, Yan-rong; Shen, Li-jun; Pang, Xiu-qin; Nie, Hong-ping; Ma, Zhi-zhong

2015-01-01

The objective of the study was to delineate clinical characteristics, surgical interventions, anatomic and visual outcomes of ruptured eye balls after trauma, and establish the prognostic indicators, which can assist clinicians in making correct surgical decisions during globe exploration for ruptured eyes. The study design used was a multicentre prospective cohort study, including six university-affiliated tertiary hospitals. We selected 242 cases of ruptured globe from the Eye Injury Vitrectomy Study database, until 31 December 2012. All selected cases underwent vitreoretinal surgery, enucleation or evisceration, and were followed up for at least 6 months. Age, visual acuity (VA) after injury, ocular trauma zone, time to surgery, corneal laceration, scleral wound, extrusion of iris or lens, ciliary body damage, intraocular haemorrhage, retinal detachment or defect, proliferative vitreoretinopathy (PVR) and choroidal damage were the predisposing factors evaluated by logistic regression models. We compared the pre-surgical indicators between cases of anatomically restored eyes with VA of 4/200 or better, or eyes with initial no light perception restored light perception or better, and cases of VA worse than 4/200, silicone oil-sustained eyes, phthisis or enucleation. Nearly 40% of cases with ruptured globe were anatomically restored through vitreoretinal surgery. The closed-funnel retinal detachment or extensive retinal loss (odds ratio [OR] = 3.38, P = 0.026), PVR-C (OR = 3.45, P = 0.008), and choroidal damage (OR = 4.20, P = 0.004) were correlated with poor outcomes. The closed-funnel retinal detachment or extensive retinal loss, PVR-C, and choroidal damage are the risk factors for unfavourable outcomes in globe ruptures. © 2015 Royal Australian and New Zealand College of Ophthalmologists.

Monozygotic twins with CAPN5 autosomal dominant neovascular inflammatory vitreoretinopathy

Directory of Open Access Journals (Sweden)

Rowell HA

2012-12-01

Full Text Available Hannah A Rowell,1,2 Alexander G Bassuk,3,4 Vinit B Mahajan1,21Omics Laboratory, 2Department of Ophthalmology and Visual Sciences, 3Department of Pediatrics, 4Department of Neurology, University of Iowa, Iowa City, IA, USABackground: The purpose of this study was to describe the clinical findings in a set of monozygotic twins with autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV over a 23-year period.Methods: A pair of female twins were examined between 26 and 49 years of age. The concordance and discordance of their clinical features were determined. The CAPN5 gene was sequenced using genomic DNA.Results: Both twins of an affected father demonstrated Stage I ADNIV with mild vitreous cells and a negative b-wave on electroretinography. Genetic analysis confirmed a guanine to thymine nucleotide (c.728G>T, pArg243Leu mutation in the CAPN5 gene. Over the course of 23 years, each twin progressed to stage III disease, showing posterior uveitis, cystoid macular edema, intraocular fibrosis, early retinal neovascularization, retinal degeneration, and cataract. Disease progression varied moderately between each twin and was asymmetrical between eyes. Twin A had 20/70 and 20/125 in the right and left eye, respectively, and underwent vitrectomy surgery and intravitreal injections with bevacizumab for recurrent cystoid macular edema. Twin B maintained 20/20 and 20/40 in the right and left eye, respectively without intervention.Conclusion: There was asymmetry between the eyes and some discordance in the rate of disease progression in these monozygotic twins with ADNIV. The overall high disease concordance suggests genetic factors play a major role in clinical manifestations in CAPN5 vitreoretinopathy.Keywords: autosomal dominant neovascular inflammatory vitreoretinopathy, ADNIV, CAPN5, calpain-5, monozygotic twins

A poliomyelitis model through mucosal infection in transgenic mice bearing human poliovirus receptor, TgPVR21

International Nuclear Information System (INIS)

Nagata, Noriyo; Iwasaki, Takuya; Ami, Yasushi; Sato, Yuko; Hatano, Ikuyoshi; Harashima, Ayako; Suzaki, Yuriko; Yoshii, Takao; Hashikawa, Tsutomu; Sata, Tetsutaro; Horiuchi, Yoshinobu; Koike, Satoshi; Kurata, Takeshi; Nomoto, Akio

2004-01-01

Transgenic mice bearing the human poliovirus receptor (TgPVR) are less susceptible to oral inoculation, although they are susceptible to parenteral inoculation. We investigated the susceptibility of TgPVR 21 line [Arch. Virol. 130 (1994) 351] to poliovirus through various mucosal routes. Intranasal inoculation of a neurovirulent Mahoney strain (OM1) caused flaccid paralysis with viral replication in the central nervous system at a dose of 10 6 cell culture infectious dose (CCID 50 ), in contrast, no paralysis following oral or intragastric inoculation of the same dose. Intranasal inoculation of a vaccine strain, Sabin 1, at 10 6 CCID 50 , resulted in no paralysis. Initial replication of poliovirus in the nasal cavity was confirmed by virus isolation and detection of negative-stranded replicative intermediates by RT-PCR and viral antigens using a high-sensitive immunohistochemistry and genome/transcripts by in situ hybridization. Poliovirus-specific IgG antibodies were elevated in the sera of surviving TgPVR21. This model can be used as a mucosal infection model and for differentiation of neurovirulent and attenuated poliovirus strains

Posterior subtenon triamcinolone acetonide in gas-filled eyes as an adjunctive treatment for complicated proliferative diabetic retinopathy.

Science.gov (United States)

Lee, Yongeun; Kang, Seungbum; Park, Young-Hoon

2013-02-01

To evaluate the effect of adjunctive subtenon injection of triamcinolone acetonide (TA) in gas-filled eyes after vitrectomy for complicated proliferative diabetic retinopathy (PDR). This nonrandomized comparative study included 27 patients (27 eyes) who underwent pars plana vitrectomy and gas tamponade for treatment of PDR with tractional or combined tractional-rhegmatogenous retinal detachment and who received subtenon injection of TA (40 mg) at the end of surgery. The study group was compared with the control group (29 eyes), which was matched with the study group for preoperative and intraoperative parameters, but underwent pars plana vitrectomy and gas tamponade without a subtenon injection of TA. Retinal reattachments without reoperation were achieved in 25 eyes (92.6%) and 26 eyes (89.7%) at 6 months (p = 1.000) in the study and control groups, respectively. The study group and the control group did not differ significantly in the frequency of postoperative proliferative vitreoretinopathy, retinal redetachment rate, reoperation rate, macular pucker formation, postoperative vitreous hemorrhage, gain in visual acuity, intraocular pressure, and intraocular inflammation (p > 0.05). The clinical results of pars plana vitrectomy for complicated PDR are not improved significantly by an adjunctive subtenon TA injection in gas-filled eyes.

Densiron® 68 as an intraocular tamponade for complex inferior retinal detachments

Directory of Open Access Journals (Sweden)

Hussain RN

2011-05-01

Full Text Available Rumana N Hussain, Somnath BanerjeeLeicester Royal Infirmary, Leicester, UKIntroduction: Densiron® 68 is a high-density liquid used to tamponade inferior retinal detachments. We present a case series of 12 patients treated with Densiron as an intraocular tamponade agent.Methods: A retrospective analysis of 12 eyes in 12 patients was carried out. The primary endpoint was anatomic reattachment of the retina following removal of Densiron oil.Results: All patients had inferior detachments; 33% had associated proliferative vitreoretinopathy (PVR. Densiron was utilized as a primary agent in five patients (42%; the remaining patients had prior unsuccessful surgery for retinal reattachment, including pars plana vitrectomy, cryotherapy, laser, encirclement, gas (C3F8 or C2F6, or silicone oil. Eleven patients (91% had successful reattachment of the retina at 3 months following removal of Densiron; one patient had extensive PVR, total retinal detachment, preretinal macula fibrosis, and chronic hypotony, and surgical intervention was unsuccessful. Six patients (50% had raised intraocular pressure (IOP, resolving in the majority of cases following Densiron removal; two patients had long-term raised IOP requiring topical or surgical therapy. Of the six phakic patients, 50% developed significant cataract in the operated eye. Of those with successful retinal reattachment, visual outcome was variable, with 36% patients gaining two to four lines on Snellen, 27% remaining objectively the same, and 36% losing one to two lines.Conclusion: The anatomic success rate is high (91% in patients requiring Densiron tamponade for inferior retinal detachments with or without evidence of PVR either as a primary or secondary intervention. A common complication is raised IOP; however, this most often resolves following removal of the oil.Keywords: intraocular tamponade, silicone oil, retinal detachment, retinal reattachments

Experimental perforating injury with high energy electrons to inhibit intraocular proliferation

International Nuclear Information System (INIS)

Velikay, M.; Binder, S.; Stolba, U.; Wedrich, AJ.; Datlinger, P.; Handl-Zeller, L.

1994-01-01

Since 1980, the fibroblast model creating experimental proliferative vitreoretinopathy has been used to evaluate the antiproliferative effect of various drugs. In previous studies radiation therapy was found to reduce effectively intraocular proliferation in this model. We therefore investigated the effect of high energy electrons in a standard perforating injury model creating a traumatic proliferative vitreoretinopathy. In 36 eyes we performed a 8 mm pars plana incision and injected 0.4 ml of 80% fibronection solution intravitreally. Ten rabbits (20 eyes) received radiation therapy with a Betatron accelerator in a total dosage of 3000 cGy to each eye divided into 10 single fractions starting on the first post-operative day. Maximum concentration of the dose was focused to the posterior vitreous. The other 9 rabbits, 18 eyes, served as control. In our perforating injury model we observed a reduction of retinal detachment rate of 72% in the controls to 55% in the treated group. The effect of radiation therapy with high energy electrons and total dosage of 3000 cGy was not statistically significant in experimental traumatic proliferative vitreoretinopathy. (au) (12 refs.)

Monozygotic twins with CAPN5 autosomal dominant neovascular inflammatory vitreoretinopathy.

Science.gov (United States)

Rowell, Hannah A; Bassuk, Alexander G; Mahajan, Vinit B

2012-01-01

The purpose of this study was to describe the clinical findings in a set of monozygotic twins with autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV) over a 23-year period. A pair of female twins were examined between 26 and 49 years of age. The concordance and discordance of their clinical features were determined. The CAPN5 gene was sequenced using genomic DNA. Both twins of an affected father demonstrated Stage I ADNIV with mild vitreous cells and a negative b-wave on electroretinography. Genetic analysis confirmed a guanine to thymine nucleotide (c.728G>T, pArg243Leu) mutation in the CAPN5 gene. Over the course of 23 years, each twin progressed to stage III disease, showing posterior uveitis, cystoid macular edema, intraocular fibrosis, early retinal neovascularization, retinal degeneration, and cataract. Disease progression varied moderately between each twin and was asymmetrical between eyes. Twin A had 20/70 and 20/125 in the right and left eye, respectively, and underwent vitrectomy surgery and intravitreal injections with bevacizumab for recurrent cystoid macular edema. Twin B maintained 20/20 and 20/40 in the right and left eye, respectively without intervention. There was asymmetry between the eyes and some discordance in the rate of disease progression in these monozygotic twins with ADNIV. The overall high disease concordance suggests genetic factors play a major role in clinical manifestations in CAPN5 vitreoretinopathy.

Pulmonary Vascular Input Impedance is a Combined Measure of Pulmonary Vascular Resistance and Stiffness and Predicts Clinical Outcomes Better than PVR Alone in Pediatric Patients with Pulmonary Hypertension

Science.gov (United States)

Hunter, Kendall S.; Lee, Po-Feng; Lanning, Craig J.; Ivy, D. Dunbar; Kirby, K. Scott; Claussen, Lori R.; Chan, K. Chen; Shandas, Robin

2011-01-01

Background Pulmonary vascular resistance (PVR) is the current standard for evaluating reactivity in children with pulmonary arterial hypertension (PAH). However, PVR measures only the mean component of right ventricular afterload and neglects pulsatile effects. We recently developed and validated an method to measure pulmonary vascular input impedance, which revealed excellent correlation between the zero-harmonic impedance value and PVR, and suggested a correlation between higher harmonic impedance values and pulmonary vascular stiffness (PVS). Here we show that input impedance can be measured routinely and easily in the catheterization laboratory, that impedance provides PVR and PVS from a single measurement, and that impedance is a better predictor of disease outcomes compared to PVR. Methods Pressure and velocity waveforms within the main PA were measured during right-heart catheterization of patients with normal PA hemodynamics (n=14) and those with PAH undergoing reactivity evaluation (49 subjects; 95 conditions). A correction factor needed to transform velocity into flow was obtained by calibrating against cardiac output. Input impedance was obtained off-line by dividing Fourier-transformed pressure and flow waveforms. Results Exceptional correlation was found between the indexed zero harmonic of impedance and indexed PVR (y=1.095·x+1.381, R2=0.9620). Additionally, the modulus sum of the first two harmonics of impedance was found to best correlate with indexed pulse pressure over stroke volume (PP/SV) (y=13.39·x-0.8058, R2=0.7962). Amongst a subset of PAH patients (n=25), cumulative logistic regression between outcomes to total indexed impedance was better (RL2=0.4012) than between outcomes and indexed PVR (RL2=0.3131). Conclusions Input impedance can be consistently and easily obtained from PW Doppler and a single catheter pressure measurement, provides comprehensive characterization of the main components of RV afterload, and better predicts patient

MicroRNA-29b regulates TGF-β1-mediated epithelial–mesenchymal transition of retinal pigment epithelial cells by targeting AKT2

Energy Technology Data Exchange (ETDEWEB)

Li, Min; Li, Hui; Liu, Xiaoqiang; Xu, Ding; Wang, Fang, E-mail: milwang_122@msn.com

2016-07-15

The role of microRNA (miRNA) in proliferative vitreoretinopathy (PVR) progression has not been studied extensively, especially in retinal pigment epithelial–mesenchymal transition (EMT) which is the main reason for formation of PVR. In this study, we first investigated the miRNA expression profile in transforming growth factor beta 1 (TGF-β1) mediated EMT of ARPE-19 cells. Among the five changed miRNAs, miR-29b showed the most significant downregulation. Enhanced expression of miR-29b could reverse TGF-β1 induced EMT through targeting Akt2. Akt2 downregulation could inhibit TGF-β1-induced EMT. Furthermore, inhibition of miR-29b in ARPE-19 cells directly triggered EMT process, which characterized by the phenotypic transition and the upregulation of α-smooth muscle actin (α-SMA) and downregulation of E-cadherin and zona occludin-1 (ZO-1) with increased cell migration. Akt2-shRNA also inhibited miR-29 inhibitor-induced EMT process. These data indicate that miR-29b plays an important role in TGF-β1-mediated EMT in ARPE-19 cells by targeting Akt2. - Highlights: • MiR-29b expression is decreased in TGF-β1-induced EMT of ARPE-19 cells. • MiR-29b inhibits TGF-β1-induced EMT in ARPE-19 cells. • MiR-29b inhibitor induces EMT in ARPE-19 cells. • Akt2 is the target for miR-29b. • Downregulation of Akt2 prevents TGF-β1-induced EMT of ARPE-19 cells.

Non-drainage scleral buckling with solid silicone elements

Directory of Open Access Journals (Sweden)

Pukhraj Rishi

2014-01-01

Full Text Available Background: With the increasing number of cataract surgeries, incidence of posterior segment complications including rhegmatogenous retinal detachment (RRD is likely to rise. Scleral buckling (SB surgery is an effective and less expensive option. The primary advantage of non-drainage procedure is avoidance of possible complications associated with trans-choroidal drainage. The aim of present study is to describe the clinical profile of subjects undergoing non-drainage SB surgery with solid silicone elements for RRD and analyze their treatment outcomes. Materials and Methods: This was a retrospective, non-randomized, interventional study at a tertiary care center. Three hundred and six eyes of 298 patients undergoing non-drainage SB surgery with solid silicone elements from year 2000 to 2006 were included. Inclusion criteria were primary RRD, peripheral depressible retinal break, media clarity affording peripheral retinal view and proliferative vitreo-retinopathy (PVR up to grade C2. Uni- and multivariate analyses was done to analyze factors affecting anatomical and visual outcomes. Statistical analysis was performed using SPSS Version 10. Results: Mean follow-up was 303 ± 393.33 days. Primary anatomical success was obtained in 279 (91.2% eyes; primary functional success in 286 (93.5% eyes. PVR (grade B or C, intraocular pressure <10 mm Hg and the inability to find a retinal break were significantly associated with final anatomical failure. Baseline vision ≤3/60 was significantly associated with poor visual recovery. Conclusions: SB surgery is reasonably safe and highly efficacious. Solid silicone elements are effective in non-drainage SB surgery. However, case selection is important.

Hybrid wide-angle viewing-endoscopic vitrectomy using a 3D visualization system

Directory of Open Access Journals (Sweden)

Kita M

2018-02-01

Full Text Available Mihori Kita, Yuki Mori, Sachiyo Hama Department of Ophthalmology, National Organization Kyoto Medical Center, Kyoto, Japan Purpose: To introduce a hybrid wide-angle viewing-endoscopic vitrectomy, which we have reported, using a 3D visualization system developed recently. Subjects and methods: We report a single center, retrospective, consecutive surgical case series of 113 eyes that underwent 25 G vitrectomy (rhegmatogenous retinal detachment or proliferative vitreoretinopathy, 49 eyes; epiretinal membrane, 18 eyes; proliferative diabetic retinopathy, 17 eyes; vitreous opacity or vitreous hemorrhage, 11 eyes; macular hole, 11 eyes; vitreomacular traction syndrome, 4 eyes; and luxation of intraocular lens, 3 eyes. Results: This system was successfully used to perform hybrid vitrectomy in the difficult cases, such as proliferative vitreoretinopathy and proliferative diabetic retinopathy. Conclusion: Hybrid wide-angle viewing-endoscopic vitrectomy using a 3D visualization system appears to be a valuable and promising method for managing various types of vitreoretinal disease. Keywords: 25 G vitrectomy, endoscope, wide-angle viewing system, 3D visualization system, hybrid

A Quantitative RNAi Screen for JNK Modifiers Identifies Pvr as a Novel Regulator of Drosophila Immune Signaling

Science.gov (United States)

Bond, David; Foley, Edan

2009-01-01

Drosophila melanogaster responds to gram-negative bacterial challenges through the IMD pathway, a signal transduction cassette that is driven by the coordinated activities of JNK, NF-κB and caspase modules. While many modifiers of NF-κB activity were identified in cell culture and in vivo assays, the regulatory apparatus that determines JNK inputs into the IMD pathway is relatively unexplored. In this manuscript, we present the first quantitative screen of the entire genome of Drosophila for novel regulators of JNK activity in the IMD pathway. We identified a large number of gene products that negatively or positively impact on JNK activation in the IMD pathway. In particular, we identified the Pvr receptor tyrosine kinase as a potent inhibitor of JNK activation. In a series of in vivo and cell culture assays, we demonstrated that activation of the IMD pathway drives JNK-dependent expression of the Pvr ligands, Pvf2 and Pvf3, which in turn act through the Pvr/ERK MAP kinase pathway to attenuate the JNK and NF-κB arms of the IMD pathway. Our data illuminate a poorly understood arm of a critical and evolutionarily conserved innate immune response. Furthermore, given the pleiotropic involvement of JNK in eukaryotic cell biology, we believe that many of the novel regulators identified in this screen are of interest beyond immune signaling. PMID:19893628

TGF-β-stimulated aberrant expression of class III β-tubulin via the ERK signaling pathway in cultured retinal pigment epithelial cells

International Nuclear Information System (INIS)

Chung, Eun Jee; Chun, Ji Na; Jung, Sun-Ah; Cho, Jin Won; Lee, Joon H.

2011-01-01

Highlights: ► TGF-β induces aberrant expression of βIII in RPE cells via the ERK pathway. ► TGF-β increases O-GlcNAc modification of βIII in RPE cells. ► Mature RPE cells have the capacity to express a neuron-associated gene by TGF-β. -- Abstract: The class III β-tubulin isotype (β III ) is expressed exclusively by neurons within the normal human retina and is not present in normal retinal pigment epithelial (RPE) cells in situ or in the early phase of primary cultures. However, aberrant expression of class III β-tubulin has been observed in passaged RPE cells and RPE cells with dedifferentiated morphology in pathologic epiretinal membranes from idiopathic macular pucker, proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR). Transforming growth factor-β (TGF-β) has been implicated in dedifferentiation of RPE cells and has a critical role in the development of proliferative vitreoretinal diseases. Here, we investigated the potential effects of TGF-β on the aberrant expression of class III β-tubulin and the intracellular signaling pathway mediating these changes. TGF-β-induced aberrant expression and O-linked-β-N-acetylglucosamine (O-GlcNac) modification of class III β-tubulin in cultured RPE cells as determined using Western blotting, RT-PCR and immunocytochemistry. TGF-β also stimulated phosphorylation of ERK. TGF-β-induced aberrant expression of class III β-tubulin was significantly reduced by pretreatment with U0126, an inhibitor of ERK phosphorylation. Our findings indicate that TGF-β stimulated aberrant expression of class III β-tubulin via activation of the ERK signaling pathway. These data demonstrate that mature RPE cells have the capacity to express a neuron-associated gene in response to TGF-β stimulation and provide useful information towards understanding the pathogenesis of proliferative vitreoretinal diseases.

TGF-{beta}-stimulated aberrant expression of class III {beta}-tubulin via the ERK signaling pathway in cultured retinal pigment epithelial cells

Energy Technology Data Exchange (ETDEWEB)

Chung, Eun Jee [Department of Ophthalmology, National Health Insurance Corporation Ilsan Hospital, Gyeonggi-do (Korea, Republic of); Chun, Ji Na; Jung, Sun-Ah [Konyang University Myunggok Medical Research Institute, Kim' s Eye Hospital, Konyang University College of Medicine, Seoul (Korea, Republic of); Cho, Jin Won [Department of Biology, Yonsei University, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-749 (Korea, Republic of); Lee, Joon H., E-mail: joonhlee@konyang.ac.kr [Konyang University Myunggok Medical Research Institute, Kim' s Eye Hospital, Konyang University College of Medicine, Seoul (Korea, Republic of)

2011-11-18

Highlights: Black-Right-Pointing-Pointer TGF-{beta} induces aberrant expression of {beta}III in RPE cells via the ERK pathway. Black-Right-Pointing-Pointer TGF-{beta} increases O-GlcNAc modification of {beta}III in RPE cells. Black-Right-Pointing-Pointer Mature RPE cells have the capacity to express a neuron-associated gene by TGF-{beta}. -- Abstract: The class III {beta}-tubulin isotype ({beta}{sub III}) is expressed exclusively by neurons within the normal human retina and is not present in normal retinal pigment epithelial (RPE) cells in situ or in the early phase of primary cultures. However, aberrant expression of class III {beta}-tubulin has been observed in passaged RPE cells and RPE cells with dedifferentiated morphology in pathologic epiretinal membranes from idiopathic macular pucker, proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR). Transforming growth factor-{beta} (TGF-{beta}) has been implicated in dedifferentiation of RPE cells and has a critical role in the development of proliferative vitreoretinal diseases. Here, we investigated the potential effects of TGF-{beta} on the aberrant expression of class III {beta}-tubulin and the intracellular signaling pathway mediating these changes. TGF-{beta}-induced aberrant expression and O-linked-{beta}-N-acetylglucosamine (O-GlcNac) modification of class III {beta}-tubulin in cultured RPE cells as determined using Western blotting, RT-PCR and immunocytochemistry. TGF-{beta} also stimulated phosphorylation of ERK. TGF-{beta}-induced aberrant expression of class III {beta}-tubulin was significantly reduced by pretreatment with U0126, an inhibitor of ERK phosphorylation. Our findings indicate that TGF-{beta} stimulated aberrant expression of class III {beta}-tubulin via activation of the ERK signaling pathway. These data demonstrate that mature RPE cells have the capacity to express a neuron-associated gene in response to TGF-{beta} stimulation and provide useful information

Galectin-3 induces clustering of CD147 and integrin-β1 transmembrane glycoprotein receptors on the RPE cell surface.

Directory of Open Access Journals (Sweden)

Claudia S Priglinger

Full Text Available Proliferative vitreoretinopathy (PVR is a blinding disease frequently occurring after retinal detachment surgery. Adhesion, migration and matrix remodeling of dedifferentiated retinal pigment epithelial (RPE cells characterize the onset of the disease. Treatment options are still restrained and identification of factors responsible for the abnormal behavior of the RPE cells will facilitate the development of novel therapeutics. Galectin-3, a carbohydrate-binding protein, was previously found to inhibit attachment and spreading of retinal pigment epithelial cells, and thus bares the potential to counteract PVR-associated cellular events. However, the identities of the corresponding cell surface glycoprotein receptor proteins on RPE cells are not known. Here we characterize RPE-specific Gal-3 containing glycoprotein complexes using a proteomic approach. Integrin-β1, integrin-α3 and CD147/EMMPRIN, a transmembrane glycoprotein implicated in regulating matrix metalloproteinase induction, were identified as potential Gal-3 interactors on RPE cell surfaces. In reciprocal immunoprecipitation experiments we confirmed that Gal-3 associated with CD147 and integrin-β1, but not with integrin-α3. Additionally, association of Gal-3 with CD147 and integrin-β1 was observed in co-localization analyses, while integrin-α3 only partially co-localized with Gal-3. Blocking of CD147 and integrin-β1 on RPE cell surfaces inhibited binding of Gal-3, whereas blocking of integrin-α3 failed to do so, suggesting that integrin-α3 is rather an indirect interactor. Importantly, Gal-3 binding promoted pronounced clustering and co-localization of CD147 and integrin-β1, with only partial association of integrin-α3. Finally, we show that RPE derived CD147 and integrin-β1, but not integrin-α3, carry predominantly β-1,6-N-actyl-D-glucosamine-branched glycans, which are high-affinity ligands for Gal-3. We conclude from these data that extracellular Gal-3 triggers

Galectin-3 Induces Clustering of CD147 and Integrin-β1 Transmembrane Glycoprotein Receptors on the RPE Cell Surface

Science.gov (United States)

Priglinger, Claudia S.; Szober, Christoph M.; Priglinger, Siegfried G.; Merl, Juliane; Euler, Kerstin N.; Kernt, Marcus; Gondi, Gabor; Behler, Jennifer; Geerlof, Arie; Kampik, Anselm; Ueffing, Marius; Hauck, Stefanie M.

2013-01-01

Proliferative vitreoretinopathy (PVR) is a blinding disease frequently occurring after retinal detachment surgery. Adhesion, migration and matrix remodeling of dedifferentiated retinal pigment epithelial (RPE) cells characterize the onset of the disease. Treatment options are still restrained and identification of factors responsible for the abnormal behavior of the RPE cells will facilitate the development of novel therapeutics. Galectin-3, a carbohydrate-binding protein, was previously found to inhibit attachment and spreading of retinal pigment epithelial cells, and thus bares the potential to counteract PVR-associated cellular events. However, the identities of the corresponding cell surface glycoprotein receptor proteins on RPE cells are not known. Here we characterize RPE-specific Gal-3 containing glycoprotein complexes using a proteomic approach. Integrin-β1, integrin-α3 and CD147/EMMPRIN, a transmembrane glycoprotein implicated in regulating matrix metalloproteinase induction, were identified as potential Gal-3 interactors on RPE cell surfaces. In reciprocal immunoprecipitation experiments we confirmed that Gal-3 associated with CD147 and integrin-β1, but not with integrin-α3. Additionally, association of Gal-3 with CD147 and integrin-β1 was observed in co-localization analyses, while integrin-α3 only partially co-localized with Gal-3. Blocking of CD147 and integrin-β1 on RPE cell surfaces inhibited binding of Gal-3, whereas blocking of integrin-α3 failed to do so, suggesting that integrin-α3 is rather an indirect interactor. Importantly, Gal-3 binding promoted pronounced clustering and co-localization of CD147 and integrin-β1, with only partial association of integrin-α3. Finally, we show that RPE derived CD147 and integrin-β1, but not integrin-α3, carry predominantly β-1,6-N-actyl-D-glucosamine-branched glycans, which are high-affinity ligands for Gal-3. We conclude from these data that extracellular Gal-3 triggers clustering of CD147 and

Vitreous-induced cytoskeletal rearrangements via the Rac1 GTPase-dependent signaling pathway in human retinal pigment epithelial cells

International Nuclear Information System (INIS)

Huang, Xionggao; Wei, Yantao; Ma, Haizhi; Zhang, Shaochong

2012-01-01

Highlights: ► Vitreous induces morphological changes and cytoskeletal rearrangements in RPE cells. ► Rac1 is activated in vitreous-transformed RPE cells. ► Rac inhibition prevents morphological changes in vitreous-transformed RPE cells. ► Rac inhibition suppresses cytoskeletal rearrangements in vitreous-transformed RPE cells. ► The vitreous-induced effects are mediated by a Rac1 GTPase/LIMK1/cofilin pathway. -- Abstract: Proliferative vitreoretinopathy (PVR) is mainly caused by retinal pigment epithelial (RPE) cell migration, invasion, proliferation and transformation into fibroblast-like cells that produce the extracellular matrix (ECM). The vitreous humor is known to play an important role in PVR. An epithelial-to-mesenchymal transdifferentiation (EMT) of human RPE cells induced by 25% vitreous treatment has been linked to stimulation of the mesenchymal phenotype, migration and invasion. Here, we characterized the effects of the vitreous on the cell morphology and cytoskeleton in human RPE cells. The signaling pathway that mediates these effects was investigated. Serum-starved RPE cells were incubated with 25% vitreous, and the morphological changes were examined by phase-contrast microscopy. Filamentous actin (F-actin) was examined by immunofluorescence and confocal microscopy. Protein phosphorylation of AKT, ERK1/2, Smad2/3, LIM kinase (LIMK) 1 and cofilin was analyzed by Western blot analysis. Vitreous treatment induced cytoskeletal rearrangements, activated Rac1 and enhanced the phosphorylation of AKT, ERK1/2 and Smad2/3. When the cells were treated with a Rac activation-specific inhibitor, the cytoskeletal rearrangements were prevented, and the phosphorylation of Smad2/3 was blocked. Vitreous treatment also enhanced the phosphorylation of LIMK1 and cofilin and the Rac inhibitor blocked this effect. We propose that vitreous-transformed human RPE cells undergo cytoskeletal rearrangements via Rac1 GTPase-dependent pathways that modulate LIMK1 and

Vitreous-induced cytoskeletal rearrangements via the Rac1 GTPase-dependent signaling pathway in human retinal pigment epithelial cells

Energy Technology Data Exchange (ETDEWEB)

Huang, Xionggao [State Key Ophthalmic Laboratory, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou (China); Department of Ophthalmology, Hainan Medical College, Haikou (China); Wei, Yantao; Ma, Haizhi [State Key Ophthalmic Laboratory, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou (China); Zhang, Shaochong, E-mail: zhshaochong@163.com [State Key Ophthalmic Laboratory, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou (China)

2012-03-09

Highlights: Black-Right-Pointing-Pointer Vitreous induces morphological changes and cytoskeletal rearrangements in RPE cells. Black-Right-Pointing-Pointer Rac1 is activated in vitreous-transformed RPE cells. Black-Right-Pointing-Pointer Rac inhibition prevents morphological changes in vitreous-transformed RPE cells. Black-Right-Pointing-Pointer Rac inhibition suppresses cytoskeletal rearrangements in vitreous-transformed RPE cells. Black-Right-Pointing-Pointer The vitreous-induced effects are mediated by a Rac1 GTPase/LIMK1/cofilin pathway. -- Abstract: Proliferative vitreoretinopathy (PVR) is mainly caused by retinal pigment epithelial (RPE) cell migration, invasion, proliferation and transformation into fibroblast-like cells that produce the extracellular matrix (ECM). The vitreous humor is known to play an important role in PVR. An epithelial-to-mesenchymal transdifferentiation (EMT) of human RPE cells induced by 25% vitreous treatment has been linked to stimulation of the mesenchymal phenotype, migration and invasion. Here, we characterized the effects of the vitreous on the cell morphology and cytoskeleton in human RPE cells. The signaling pathway that mediates these effects was investigated. Serum-starved RPE cells were incubated with 25% vitreous, and the morphological changes were examined by phase-contrast microscopy. Filamentous actin (F-actin) was examined by immunofluorescence and confocal microscopy. Protein phosphorylation of AKT, ERK1/2, Smad2/3, LIM kinase (LIMK) 1 and cofilin was analyzed by Western blot analysis. Vitreous treatment induced cytoskeletal rearrangements, activated Rac1 and enhanced the phosphorylation of AKT, ERK1/2 and Smad2/3. When the cells were treated with a Rac activation-specific inhibitor, the cytoskeletal rearrangements were prevented, and the phosphorylation of Smad2/3 was blocked. Vitreous treatment also enhanced the phosphorylation of LIMK1 and cofilin and the Rac inhibitor blocked this effect. We propose that vitreous

Overexpression of Snail in retinal pigment epithelial triggered epithelial–mesenchymal transition

International Nuclear Information System (INIS)

Li, Hui; Li, Min; Xu, Ding; Zhao, Chun; Liu, Guodong; Wang, Fang

2014-01-01

Highlights: • First reported overexpression of Snail in RPE cells could directly trigger EMT. • Further confirmed the regulator role of Snail in RPE cells EMT in vitro. • Snail may be a potential therapeutic target to prevent the fibrosis of PVR. - Abstract: Snail transcription factor has been implicated as an important regulator in epithelial–mesenchymal transition (EMT) during tumourigenesis and fibrogenesis. Our previous work showed that Snail transcription factor was activated in transforming growth factor β1 (TGF-β1) induced EMT in retinal pigment epithelial (RPE) cells and may contribute to the development of retinal fibrotic disease such as proliferative vitreoretinopathy (PVR). However, whether Snail alone has a direct role on retinal pigment epithelial–mesenchymal transition has not been investigated. Here, we analyzed the capacity of Snail to drive EMT in human RPE cells. A vector encoding Snail gene or an empty vector were transfected into human RPE cell lines ARPE-19 respectively. Snail overexpression in ARPE-19 cells resulted in EMT, which was characterized by the expected phenotypic transition from a typical epithelial morphology to mesenchymal spindle-shaped. The expression of epithelial markers E-cadherin and Zona occludin-1 (ZO-1) were down-regulated, whereas mesenchymal markers a-smooth muscle actin (a-SMA) and fibronectin were up-regulated in Snail expression vector transfected cells. In addition, ectopic expression of Snail significantly enhanced ARPE-19 cell motility and migration. The present data suggest that overexpression of Snail in ARPE-19 cells could directly trigger EMT. These results may provide novel insight into understanding the regulator role of Snail in the development of retinal pigment epithelial–mesenchymal transition

Fisetin inhibits epidermal growth factor-induced migration of ARPE-19 cells by suppression of AKT activation and Sp1-dependent MMP-9 expression.

Science.gov (United States)

Lin, Hung-Yu; Chen, Yong-Syuan; Wang, Kai; Chien, Hsiang-Wen; Hsieh, Yi-Hsien; Yang, Shun-Fa

2017-01-01

Proliferative vitreoretinopathy (PVR) can result in abnormal migration of RPE cells. Fisetin is a naturally occurring compound that has been reported to have antitumor effects, but its effects on epidermal growth factor (EGF)-induced cell migration and the underlying mechanisms remain unclear. Effects of fisetin on EGF-induced cell viability and migration were examined with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and in vitro migration assays. Reverse transcription-PCR (RT-PCR) and immunoblotting were performed to evaluate matrix metallopeptidase-9 (MMP-9) expression and activation of specificity protein-1 (Sp1) and protein kinase B (AKT) in ARPE-19 cells treated with EGF and with or without fisetin. Luciferase and chromatin immunoprecipitation (ChIP) assays were performed to examine Sp1 transcription activity and MMP-9 binding activity. Fisetin did not affect ARPE-19 cell viability and significantly inhibited the EGF-induced migration capacity of ARPE-19 cells. Furthermore, fisetin exerted an antimigratory effect and suppressed MMP-9 mRNA and protein expression. Treatment with EGF induced phosphorylation of AKT and expression of MMP-9 and Sp1. Fisetin combined with LY294002 (an inhibitor of AKT) prevented the EGF-induced migration involved in downregulation of Sp1 and MMP-9 expression. Luciferase and ChIP assays suggested that fisetin remarkably decreased the EGF-induced transcription activity of MMP-9 and Sp1 and inhibited EGF-mediated Sp1 from directly binding to the MMP-9 promoter in ARPE-19 cells. Fisetin inhibited EGF-induced cell migration via modulation of AKT/Sp1-dependent MMP-9 transcriptional activity. Therefore, fisetin may be a potential agent in the treatment of migratory PVR diseases.

Predictors of treatment failure for pneumatic retinopexy.

Science.gov (United States)

Rootman, Dan B; Luu, Shelly; M Conti, Stephen; Mandell, Mark; Devenyi, Robert; Lam, Wai-Ching; Kertes, Peter J

2013-12-01

The purpose of this study was to define the overall anatomic success rate in pneumatic retinopexy and to identify morphologic features that may be predictive of treatment failure in pneumatic retinopexy. Prospective consecutive interventional case series of patients with new-onset primary rhegmatogenous retinal detachments treated with pneumatic retinopexy. In this interventional case series, consecutive patients with new-onset primary rhegmatogenous retinal detachments were treated with pneumatic retinopexy and followed prospectively. Morphologic data were collected on 3-colour fundus drawings. The primary outcome measure was treatment failure, defined as requirement for scleral buckle or vitrectomy within the follow-up period. Rates of failure for each morphologic feature were compared and a logistic regression model was fit. A total of 113 eyes were included in the study. Anatomic success was achieved in 69.6% of patients. Morphologic criteria including the position and number of breaks, position and extent of lattice degeneration, size of the detached area, and macular status were all found not to be significantly related to failure. In multivariate analysis, only 3 predictors, pseudophakic status (p < 0.05, odds ratio [OR] 2.9, 95% CI, 1.06-7.88), presence of retinal break greater than 1 clock-hour (p < 0.05, OR 3.41, 1.06-11.02), and presence of grade C or D proliferative vitreoretinopathy (PVR) (p < 0.01, OR 31.83, 95% CI, 3.59-282.24), gained statistical significance. Only pseudophakia, a large retinal break, and/or PVR was associated with an increased likelihood of failure. Copyright © 2013 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

Demarcation laser photocoagulation of selected macula-sparing rhegmatogenous retinal detachments.

Science.gov (United States)

Vrabec, T R; Baumal, C R

2000-06-01

To report a series of macula-sparing rhegmatogenous retinal detachments (MSRRDs) treated with demarcation laser photocoagulation (DLP). Retrospective, noncomparative case series. Thirty-one patients (34 eyes) with primary or recurrent MSRRDs without associated visual field loss, necrotizing retinitis, or proliferative vitreoretinopathy (PVR), managed with DLP from November 1992 through May 1999. Demarcation laser photocoagulation consisting of a triple row of confluent laser burns. Best corrected postoperative visual acuity and MSRRD progression or recurrence. Thirty-four primary and recurrent MSRRDs were treated by DLP, which consisted of a triple row of confluent laser burns. Macula-sparing rhegmatogenous retinal detachments were located in all quadrants and affected 10% to 45% of the retina. Findings associated with MSRRDs included lattice degeneration (12 eyes), vitreous hemorrhage (4 eyes), and demarcation line (9 eyes). Symptoms (photopsias or floaters) were associated with 14 MSRRDs. Eight eyes were myopic and 11 were pseudophakic. Thirty-two MSRRDs were shallow, two were dome shaped, and all were smooth without corrugations. Follow-up ranged from 1.5 to 80 months (mean, 15.8 months; median, 17 months). Thirty-three of 34 detachments remained stable after DLP. Three flattened spontaneously. One eye was managed with scleral buckle 6 weeks after DLP. Progression was attributed to incomplete laser treatment. Best corrected postoperative visual acuity was the same or improved in all but one eye, in which a cataract developed. Demarcation laser photocoagulation is an effective method to manage acute or chronic, primary or recurrent MSRRDs without associated PVR that are shallow and smooth without corrugations. Demarcation laser photocoagulation is an alternative to both observation and surgical repair for these select MSRRDs.

ZNF408 is mutated in familial exudative vitreoretinopathy and is crucial for the development of zebrafish retinal vasculature

NARCIS (Netherlands)

Collin, R.W.J.; Nikopoulos, K.; Dona, M.A.; Gilissen, C.F.H.A.; Hoischen, A.; Boonstra, F.N.; Poulter, J.A.; Kondo, H.; Berger, W.; Toomes, C.; Tahira, T.; Mohn, L.R.; Blokland, E.A.W.; Hetterschijt, L.; Ali, M.; Groothuismink, J.M.; Duijkers, L.E.M.; Inglehearn, C.F.; Sollfrank, L.; Strom, T.M.; Uchio, E.; Nouhuys, C.E. van; Kremer, H.; Veltman, J.A.; Wijk, E. van; Cremers, F.P.M.

2013-01-01

Familial exudative vitreoretinopathy (FEVR) is a genetically heterogeneous disorder characterized by abnormal vascularization of the peripheral retina, which can result in retinal detachment and severe visual impairment. In a large Dutch FEVR family, we performed linkage analysis, exome sequencing,

GSK3β attenuates TGF-β1 induced epithelial–mesenchymal transition and metabolic alterations in ARPE-19 cells

International Nuclear Information System (INIS)

Huang, Li; Zhang, Cheng; Su, Li; Song, Zhengyu

2017-01-01

While TGF-β1 is known to induce epithelial–mesenchymal transition (EMT), a major factor in the pathogenesis of proliferative vitreoretinopathy (PVR), in ARPE-19 cells. The molecular pathways involved in EMT formation have not yet to be fully characterized. In this study, we have found that TGF-β1-mediated induction of EMT in ARPE-19 cells varied in a dose- and time-dependent manner. Specifically, TGF-β1 inhibited GSK-3β by accelerating phosphorylation at ser9. GSK-3β inhibitor or knockdown of GSK-3β resulted in enhanced TGF-β1-mediated EMT, migration and collagen contraction in ARPE-19 cells, which were then abrogated by GSK-3β overexpression and PI3K/AKT inhibitor. Importantly, GSK-3β also mediated metabolic reprogramming in TGF-β1-treated cells. Our results indicate that GSK-3β plays a pivotal role in TGF-β1-mediated EMT in ARPE-19 cells. - Highlights: • GSK-3β mediates epithelial-mesenchymal transition in TGF-β1 treated ARPE-19 cells. • GSK-3β regulates cell migration and collagen contraction of ARPE-19 cells. • TGF-β1 induces extracellular metabolomic changes of ARPE-19 cells via a GSK-3β-dependent mechanism.

Heavy Silicone Oil and Intraocular Inflammation

Directory of Open Access Journals (Sweden)

Francesco Morescalchi

2014-01-01

Full Text Available In the past two decades, many advances have been made in vitrectomy instrumentation, surgical techniques, and the use of different tamponade agents. These agents serve close retinal breaks, confine eventual retinal redetachment, and prevent proliferative vitreoretinopathy (PVR. Long-acting gases and silicone oil are effective internal tamponade agents; however, because their specific gravity is lower than that of the vitreous fluid, they may provide adequate support for the superior retina but lack efficacy for the inferior retina, especially when the fill is subtotal. Thus, a specific role may exist for an internal tamponade agent with a higher specific gravity, such as heavy silicone oils (HSOs, Densiron 68, Oxane HD, HWS 45-300, HWS 46-3000, and HeavySil. Some clinical evidence seems to presume that heavy tamponades are more prone to intraocular inflammation than standard silicone if they remain in the eye for several months. In this review, we discuss the fundamental clinical and biochemical/molecular mechanisms involved in the inflammatory response after the use of heavy tamponade: toxicity due to impurities or instability of the agent, direct toxicity and immunogenicity, oil emulsification, and mechanical injury due to gravity. The physical and chemical properties of various HSOs and their efficacy and safety profiles are also described.

The Wnt signaling pathway in familial exudative vitreoretinopathy and Norrie disease.

Science.gov (United States)

Warden, Scott M; Andreoli, Christopher M; Mukai, Shizuo

2007-01-01

The Wnt signaling pathway is highly conserved among species and has an important role in many cell biological processes throughout the body. This signaling cascade is involved in regulating ocular growth and development, and recent findings indicate that this is particularly true in the retina. Mutations involving different aspects of the Wnt signaling pathway are being linked to several diseases of retinal development. The aim of this article is to first review the Wnt signaling pathway. We will then describe two conditions, familial exudative vitreoretinopathy (FEVR) and Norrie disease (ND), which have been shown to be caused in part by defects in the Wnt signaling cascade.

Fisetin inhibits epidermal growth factor–induced migration of ARPE-19 cells by suppression of AKT activation and Sp1-dependent MMP-9 expression

Science.gov (United States)

Lin, Hung-Yu; Chen, Yong-Syuan; Wang, Kai; Chien, Hsiang-Wen

2017-01-01

Purpose Proliferative vitreoretinopathy (PVR) can result in abnormal migration of RPE cells. Fisetin is a naturally occurring compound that has been reported to have antitumor effects, but its effects on epidermal growth factor (EGF)–induced cell migration and the underlying mechanisms remain unclear. Methods Effects of fisetin on EGF-induced cell viability and migration were examined with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and in vitro migration assays. Reverse transcription–PCR (RT–PCR) and immunoblotting were performed to evaluate matrix metallopeptidase-9 (MMP-9) expression and activation of specificity protein-1 (Sp1) and protein kinase B (AKT) in ARPE-19 cells treated with EGF and with or without fisetin. Luciferase and chromatin immunoprecipitation (ChIP) assays were performed to examine Sp1 transcription activity and MMP-9 binding activity. Results Fisetin did not affect ARPE-19 cell viability and significantly inhibited the EGF-induced migration capacity of ARPE-19 cells. Furthermore, fisetin exerted an antimigratory effect and suppressed MMP-9 mRNA and protein expression. Treatment with EGF induced phosphorylation of AKT and expression of MMP-9 and Sp1. Fisetin combined with LY294002 (an inhibitor of AKT) prevented the EGF-induced migration involved in downregulation of Sp1 and MMP-9 expression. Luciferase and ChIP assays suggested that fisetin remarkably decreased the EGF-induced transcription activity of MMP-9 and Sp1 and inhibited EGF-mediated Sp1 from directly binding to the MMP-9 promoter in ARPE-19 cells. Conclusions Fisetin inhibited EGF-induced cell migration via modulation of AKT/Sp1–dependent MMP-9 transcriptional activity. Therefore, fisetin may be a potential agent in the treatment of migratory PVR diseases. PMID:29296070

Characteristics and Surgical Outcomes of Rhegmatogenous Retinal Detachment Following Myopic LASIK

Science.gov (United States)

Daftarian, Narsis; Dehghan, Mohammad-Hossein; Ahmadieh, Hamid; Soheilian, Masoud; Karkhaneh, Reza; Lashay, Alireza; Mirshahi, Ahmad; Parhizkar, Hamid; Kazemimoghadam, Mohsen; Modarreszadeh, Mehdi; Hashemi, Masih; Fadaei, Mojtaba; Entezari, Morteza

2009-01-01

Purpose To describe the clinical features and surgical outcomes of rhegmatogenous retinal detachment (RRD) following myopic laser in situ keratomileusis (LASIK). Methods In a retrospective, non-comparative case series, 46 eyes that had undergone vitreoretinal surgery for management of RRD following myopic LASIK were identified. Data was reviewed with emphasis on characteristics of the RRD, employed surgical techniques, and anatomic and visual outcomes. Results Mean pre-LASIK myopia was −9.7±3.9 (range −4.00 to −18.00) diopters (D). Mean interval between LASIK and development of RRD was 11.6±11.2 months. Posterior vitreous detachment was present in 44 eyes (95.6%). The retinal breaks included flap tears in 36 (78.3%) eyes, giant tears in 8 (17.4%) eyes and atrophic holes in 2 (4.3%) eyes. In eyes with flap tears, the breaks were multiple, large or posterior to the equator in 24(66.7%) eyes. Retinal breaks were related to lattice degeneration in 20 (43.5%) eyes of which, three had history of prophylactic barrier laser photocoagulation. Scleral buckling was performed as the initial procedure in 32 (69.6%) eyes and primary vitrectomy was undertaken in 14 (30.4%) eyes. The initial surgical procedure failed in 14 (30.4%) eyes due to proliferative vitreoretinopathy (PVR). Retinal reattachment was finally achieved in 43 (93.4%) eyes. Postoperative visual acuity ≥20/40 and ≥20/200 was achieved in 16 (34.8%) and 25 (54.3%) eyes, respectively. Conclusion Post-LASIK retinal detachment has a complex nature in eyes with moderate to high myopia. The retinal detachment is complex in terms of size, number and location of retinal breaks, is associated with a high rate of PVR and entails unfavorable visual outcomes. PMID:23198065

Complex genetics of familial exudative vitreoretinopathy and related pediatric retinal detachments

Science.gov (United States)

Kondo, Hiroyuki

2015-01-01

Familial exudative vitreoretinopathy (FEVR) is a hereditary vitreoretinal disorder that can cause various types of retinal detachments. The abnormalities in eyes with FEVR are caused by poor vascularization in the peripheral retina. The genetics of FEVR is highly heterogeneous, and mutations in the genes for Wnt signaling and a transcription factor have been reported to be responsible for FEVR. These factors have been shown to be the regulators of the pathophysiological pathways of retinal vascular development. Studies conducted to identify the causative genes of FEVR have uncovered a diverse and complex relationship between FEVR and other diseases; for example, Norrie disease, a Mendelian-inherited disease; retinopathy of prematurity, a multifactorial genetic disease; and Coats disease, a nongenetic disease, associated with pediatric retinal detachments. PMID:29018668

Clinical presentation of familial exudative vitreoretinopathy.

Science.gov (United States)

Ranchod, Tushar M; Ho, Lawrence Y; Drenser, Kimberly A; Capone, Antonio; Trese, Michael T

2011-10-01

To describe the clinical characteristics, staging and presentation of patients with familial exudative vitreoretinopathy (FEVR) in our clinical practice over the last 25 years. Case series, retrospective review. We included 273 eyes of 145 patients. Data collected from charts included gender, gestational age at birth, birthweight, age at presentation, referring diagnosis, family history, prior ocular surgery, and clinical presentation in each eye. Eyes with invasive posterior segment procedures before initial presentation were excluded. Demographics on presentation and clinical staging. Patients were slightly male predominant (57%) with a mean birthweight of 2.80 kg (range, 740 g-4.76 kg), mean gestational age of 37.8 weeks (range, 25-42), and mean age at presentation of almost 6 years (range, presentation, gestational age, and birthweight. Although a positive family history on presentation may support the diagnosis of FEVR, a negative family history is of little help. The majority of retinal folds extended radially in the temporal quadrants, but radial folds were seen in almost all quadrants. Fellow eyes demonstrated a wide variation in symmetry. The presentation of FEVR may mimic the presentation of other pediatric and adult vitreoretinal disorders, and careful examination is often crucial in making the diagnosis of FEVR. The authors have no proprietary or commercial interest in any of the materials discussed in this article. Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Transjugular portal vein recanalization with creation of intrahepatic portosystemic shunt (PVR-TIPS) in patients with chronic non-cirrhotic, non-malignant portal vein thrombosis.

Science.gov (United States)

Klinger, Christoph; Riecken, Bettina; Schmidt, Arthur; De Gottardi, Andrea; Meier, Benjamin; Bosch, Jaime; Caca, Karel

2018-03-01

To determine safety and efficacy of transjugular portal vein recanalization with creation of intrahepatic portosystemic shunt (PVR-TIPS) in patients with chronic non-cirrhotic, non-malignant portal vein thrombosis (PVT). This retrospective study includes 17 consecutive patients with chronic non-cirrhotic PVT (cavernous transformation n = 15). PVR-TIPS was indicated because of variceal bleeding (n = 13), refractory ascites (n = 2), portal biliopathy with recurrent cholangitis (n = 1), or abdominal pain (n = 1). Treatment consisted of a combination of transjugular balloon angioplasty, mechanical thrombectomy, and-depending on extent of residual thrombosis-transjugular intrahepatic portosystemic shunt and additional stenting of the portal venous system. Recanalization was successful in 76.5 % of patients despite cavernous transformation in 88.2 %. Both 1- and 2-year secondary PV and TIPS patency rates were 69.5 %. Procedure-related bleeding complications occurred in 2 patients (intraperitoneal bleeding due to capsule perforation, n = 1; liver hematoma, n = 1) and resolved spontaneously. However, 1 patient died due to subsequent nosocomial pneumonia. During follow-up, 3 patients with TIPS occlusion and PVT recurrence experienced portal hypertensive complications. PVR-TIPS is safe and effective in selected patients with chronic non-cirrhotic PVT. Due to technical complexity and possible complications, it should be performed only in specialized centers with high experience in TIPS procedures. © Georg Thieme Verlag KG Stuttgart · New York.

F6H8 as an Intraoperative Tool and F6H8/Silicone Oil as a Postoperative Tamponade in Inferior Retinal Detachment with Inferior PVR

Directory of Open Access Journals (Sweden)

Gian Marco Tosi

2014-01-01

Full Text Available Purpose. To evaluate the effectiveness and safety of perfluorohexyloctane (F6H8 for intraoperative flattening of the retina and of F6H8/silicone oil (SO 1000 cSt as a postoperative tamponade for inferior retinal detachment with inferior proliferative vitreoretinopathy. Methods. This is a retrospective review of 22 patients who underwent pars plana vitrectomy using F6H8 as an intraoperative tool to flatten the retina. At the end of the surgery a direct partial exchange between F6H8 and SO 1000 cSt was performed, tamponing the eye with different ratios of F6H8/SO (70/30, 60/40, 50/50, 40/30, and 30/70. Anatomical and functional results and complications were evaluated over the follow-up period (mean 22.63 months. Results. F6H8 was efficacious for intraoperative flattening of the retina. Twenty-one of the 22 patients achieved a complete retinal reattachment. Postoperative visual acuity (VA ranged from light perception to 20/70, with 72% of patients obtaining VA better than 20/400. No emulsification/inflammation was observed whatever the ratio of F6H8/SO used. With higher ratios of F6H8/SO (70/30 and 60/40 cloudiness of the tamponade was observed. A transparent mixture was present with all the other ratios. Conclusions. The surgical technique adopted is very simple and safe. The optimal F6H8/SO ratio seems to be between 50/50 and 30/70.

Lack of a differential radiation response for proliferative and non-proliferative rat thyroid cells (FRTL-5) in vitro

International Nuclear Information System (INIS)

Brosing, J.W.; Giese, W.L.; Mulcahy, R.T.

1989-01-01

FRTL-5 rat thyroid epithelial cells maintain normal thyroid function and morphology in vitro, exhibit an absolute requirement for thyroid stimulating hormone (TSH) for proliferation and display radiation dose response characteristics indistinguishable from those of rat thyroid epithelial cells in vivo. In TSH-free medium cells remain in a non-proliferative, yet viable, state for prolonged periods of time and respond to TSH re-stimulation by a return to exponential growth. Flow cytometric analysis using two-step acridine orange (AO) staining revealed an accumulation of cells in the G1 phase of the cell cycle accompanied by a pronounced reduction in red fluorescence (indicative of RNA content) in FRTL-5 cells cultured in the absence of TSH. The response of proliferative and non-proliferative FRTL-5 cells to single dose, split dose and fractionated radiation was compared to determine whether proliferative status was an important response determinant. The response of FRTL-5 cells was not influenced by proliferative status at the time of irradiation. Additionally, dose response was not altered by variable (12 hr-8 days) non-proliferative intervals before or after irradiation. As revealed by split dose experiments, the rate and extent of sublethal damage repair was likewise similar for proliferative and non-proliferative cells. Multifraction experiments employing three fractions separated by 6 hr intervals indicate that non-proliferative FRTL-5 cells completely repair sublethal damage between fractions. These results indicate that the radiation response of FRTL-5 cells is not influenced by the proliferative status of the cells prior to or post-irradiation

TNF-α promotes human retinal pigment epithelial (RPE) cell migration by inducing matrix metallopeptidase 9 (MMP-9) expression through activation of Akt/mTORC1 signaling

International Nuclear Information System (INIS)

Wang, Cheng-hu; Cao, Guo-Fan; Jiang, Qin; Yao, Jin

2012-01-01

Highlights: ► TNF-α induces MMP-9 expression and secretion to promote RPE cell migration. ► MAPK activation is not critical for TNF-α-induced MMP-9 expression. ► Akt and mTORC1 signaling mediate TNF-α-induced MMP-9 expression. ► SIN1 knockdown showed no significant effect on MMP-9 expression by TNF-α. -- Abstract: Tumor necrosis factor-alpha (TNF-α) promotes in vitro retinal pigment epithelial (RPE) cell migration to initiate proliferative vitreoretinopathy (PVR). Here we report that TNF-α promotes human RPE cell migration by inducing matrix metallopeptidase 9 (MMP-9) expression. Inhibition of MMP-9 by its inhibitor or its neutralizing antibody inhibited TNF-α-induced in vitro RPE cell migration. Reversely, exogenously-added active MMP-9 promoted RPE cell migration. Suppression Akt/mTOR complex 1(mTORC1) activation by LY 294002 and rapamycin inhibited TNF-α-mediated MMP-9 expression. To introduce a constitutively active Akt (CA-Akt) in cultured RPE cells increased MMP-9 expression, and to block mTORC1 activation by rapamycin inhibited its effect. RNA interference (RNAi)-mediated silencing of SIN1, a key component of mTOR complex 2 (mTORC2), had no effect on MMP-9 expression or secretion. In conclusion, this study suggest that TNF-α promotes RPE cell migration by inducing MMP-9 expression through activation of Akt/ mTORC1, but not mTORC2 signaling.

[Internal limiting membrane peeling as prophylaxis of epimacular membrane formation in eyes undergoing vitrectomy for rhegmatogenous retinal detachement].

Science.gov (United States)

Hejsek, L; Dusová, J; Stepanov, A; Rozsíval, P

2014-06-01

Rhegmatogenous retinal detachment is a serious condition that can significantly impair visual function, even after a successful surgery. One of the complications that can significantly impair visual acuity in the postoperative period is a development of the epimacular membrane (ERM). The aim of this work is to monitor the effect of peeling of the internal limiting membrane (ILM) in the macula at the anatomical and functional results in the postoperative period, especially with regard to the development of ERM. Prospective study of 21 eyes, which underwent peeling of ILM during pars plana vitrectomy for rhegmatogenous retinal detachment (on detached macula). The ILM peeling was done without using decalin during this procedure. We tested best corrected visual acuity (BCVA) and followed fundus biomicroscopic findings. Proliferative vitreoretinopathy (PVR) was evaluated according to the recommendations of the Retina Society Terminology Committee. To exclude the development of ERM in the macula optical coherence tomography (OCT) was performed at the end of the 18-month follow-up period. In total, the results of 21 eyes of 21 patients who underwent PPV for rhegmatogenous retinal detachment were evaluated. In all of them was during PPV performed ILM peeling on detached macula, these are followed prospectively. ILM peeling without using decalin was sufficient in all eyes. All eyes with ILM peeling did not develop ERM at the end of the follow-up period. ILM peeling during PPV for rhegmatogenous retinal detachment reduces the risk of developing secondary ERM.

TNF-{alpha} promotes human retinal pigment epithelial (RPE) cell migration by inducing matrix metallopeptidase 9 (MMP-9) expression through activation of Akt/mTORC1 signaling

Energy Technology Data Exchange (ETDEWEB)

Wang, Cheng-hu; Cao, Guo-Fan [The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029 (China); Jiang, Qin, E-mail: Jqin710@vip.sina.com [The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029 (China); Yao, Jin, E-mail: dryaojin@yahoo.com [The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029 (China)

2012-08-17

Highlights: Black-Right-Pointing-Pointer TNF-{alpha} induces MMP-9 expression and secretion to promote RPE cell migration. Black-Right-Pointing-Pointer MAPK activation is not critical for TNF-{alpha}-induced MMP-9 expression. Black-Right-Pointing-Pointer Akt and mTORC1 signaling mediate TNF-{alpha}-induced MMP-9 expression. Black-Right-Pointing-Pointer SIN1 knockdown showed no significant effect on MMP-9 expression by TNF-{alpha}. -- Abstract: Tumor necrosis factor-alpha (TNF-{alpha}) promotes in vitro retinal pigment epithelial (RPE) cell migration to initiate proliferative vitreoretinopathy (PVR). Here we report that TNF-{alpha} promotes human RPE cell migration by inducing matrix metallopeptidase 9 (MMP-9) expression. Inhibition of MMP-9 by its inhibitor or its neutralizing antibody inhibited TNF-{alpha}-induced in vitro RPE cell migration. Reversely, exogenously-added active MMP-9 promoted RPE cell migration. Suppression Akt/mTOR complex 1(mTORC1) activation by LY 294002 and rapamycin inhibited TNF-{alpha}-mediated MMP-9 expression. To introduce a constitutively active Akt (CA-Akt) in cultured RPE cells increased MMP-9 expression, and to block mTORC1 activation by rapamycin inhibited its effect. RNA interference (RNAi)-mediated silencing of SIN1, a key component of mTOR complex 2 (mTORC2), had no effect on MMP-9 expression or secretion. In conclusion, this study suggest that TNF-{alpha} promotes RPE cell migration by inducing MMP-9 expression through activation of Akt/ mTORC1, but not mTORC2 signaling.

Novel mutations in Norrie disease gene in Japanese patients with Norrie disease and familial exudative vitreoretinopathy.

Science.gov (United States)

Kondo, Hiroyuki; Qin, Minghui; Kusaka, Shunji; Tahira, Tomoko; Hasebe, Haruyuki; Hayashi, Hideyuki; Uchio, Eiichi; Hayashi, Kenshi

2007-03-01

To search for mutations in the Norrie disease gene (NDP) in Japanese patients with familial exudative vitreoretinopathy (FEVR) and Norrie disease (ND) and to delineate the mutation-associated clinical features. Direct sequencing after polymerase chain reaction of all exons of the NDP gene was performed on blood collected from 62 probands (31 familial and 31 simplex) with FEVR, from 3 probands with ND, and from some of their family members. The clinical symptoms and signs in the patients with mutations were assessed. X-inactivation in the female carriers was examined in three FEVR families by using leukocyte DNA. Four novel mutations-I18K, K54N, R115L, and IVS2-1G-->A-and one reported mutation, R97P, in the NDP gene were identified in six families. The severity of vitreoretinopathy varied among these patients. Three probands with either K54N or R115L had typical features of FEVR, whereas the proband with R97P had those of ND. Families with IVS2-1G-->A exhibited either ND or FEVR characteristics. A proband with I18K presented with significant phenotypic heterogeneity between the two eyes. In addition, affected female carriers in a family harboring the K54N mutation presented with different degrees of vascular abnormalities in the periphery of the retina. X-inactivation profiles indicated that the skewing was not significantly different between affected and unaffected women. These observations indicate that mutations of the NDP gene can cause ND and 6% of FEVR cases in the Japanese population. The X-inactivation assay with leukocytes may not be predictive of the presence of a mutation in affected female carriers.

Proliferative retinopathy predicts nephropathy

DEFF Research Database (Denmark)

Karlberg, Charlotte; Falk, Christine; Green, Anders

2012-01-01

We wanted to examine proliferative retinopathy as a marker of incident nephropathy in a 25-year follow-up study of a population-based cohort of Danish type 1 diabetic patients and to examine cross-sectional associations between nephropathy and retinopathy in long-term surviving patients of the same...... cohort. All type 1 diabetic patients from Fyn County, Denmark, were identified as of 1 July 1973. One hundred and eighty four patients were examined in 1981-1982 (baseline) and in 2007-2008 (follow-up). The level of retinopathy was graded by ophthalmoscopy at baseline and nine-field digital colour fundus...... and proliferative retinopathy, respectively. In conclusion, proliferative retinopathy is an independent marker of long-term nephropathy in type 1 diabetes. Upcoming studies should examine whether these microvascular complications are also causally linked in type 1 diabetes....

Non-Proliferative Diabetic Retinopathy Vision Simulator

Science.gov (United States)

... Oncology Oculoplastics/Orbit Refractive Management/Intervention Retina/Vitreous Uveitis Focus On Pediatric Ophthalmology ... Retinopathy Diagnosis Diabetic Retinopathy Treatment Proliferative Diabetic Retinopathy Vision Simulator Non-Proliferative Diabetic ...

Pathological study on the process of proliferative vireoretinopahy - PVR - after retinal detachment

OpenAIRE

Yamashita, Hidetoshi

1986-01-01

学位取得大学: 東京大学; 報告番号: 乙第8071号; 学位授与年月日: 1986-11-26; 学位の種別: 論文博士; 学位の種類: 医学博士　「Japanese Journal of Opthalmology Vol.30, 1986, p.269-281, Vol.29, 1985, p.42-53, Vol.29, 1985, p.394-405」に掲載されたもの

Anatomical success in patients after retinectomy for complex retinal detachment

International Nuclear Information System (INIS)

Mukhtar, A.; Ishaq, M.; Islam, Q.U.

2015-01-01

To evaluate the efficacy of primary and redo retinectomy in eyes with complex retinal detachment. Study Design: Quasi-experimental study. Place and Duration of Study: Armed Forces Institute of Ophthalmology Rawalpindi from Jan 2012 to June 2013. Patients and Methods: Fifty eight eyes (patients) underwent relaxing retinectomies for complex retinal detachment with proliferative vitreoretinopathy or intrinsic retinal shortening. Operative technique included pars plana vitrectomy, proliferative vitreoretinopathy management, use of intraoperative perfluorocarbon liquid, retinectomy, endolaser and intraocular temponade. The main outcome was anatomic success, defined as complete retinal reattachment at four months follow up. Eighteen eyes out of the same primary group underwent second retinectomy because of anatomical failure. Results: Mean age of study population was 53.78 ± 15.11 years, 56.9% of patients were male(s). Anatomic success rate after 1st retinectomy was achieved in 68.96% (40 eyes out of 58). In eighteen eyes that underwent 2nd retinectomy, anatomic success rate was 72.22% (13 eyes out of 18). Overall success rate was 91.3% (53 eyes out of 58) in our study. Conclusions: Relaxing retinectomies for retinal shortening can improve the anatomical success rate in patients with complex RD. (author)

A mutation in the Norrie disease gene (NDP) associated with X-linked familial exudative vitreoretinopathy.

Science.gov (United States)

Chen, Z Y; Battinelli, E M; Fielder, A; Bundey, S; Sims, K; Breakefield, X O; Craig, I W

1993-10-01

Familial exudative vitreoretinopathy (FEVR) is a hereditary disorder characterized by an abnormality of the peripheral retina. Both autosomal dominant (adFEVR) and X-linked (XLFEVR) forms have been described, but the biochemical defect(s) underlying the symptoms are unknown. Molecular analysis of the Norrie gene locus (NDP) in a four generation FEVR family (shown previously to exhibit linkage to the X-chromosome markers DXS228 and MAOA (Xp11.4-p11.3)) reveals a missense mutation in the highly conserved region of the NDP gene, which caused a neutral amino acid substitution (Leu124Phe), was detected in all of the affected males, but not in the unaffected family members, nor in normal controls. The observations suggest that phenotypes of both XLFEVR and Norrie disease can result from mutations in the same gene.

Genetic heterogeneity in familial exudative vitreoretinopathy; exclusion of the EVR1 locus on chromosome 11q in a large autosomal dominant pedigree

OpenAIRE

Bamashmus, M; Downey, L; Inglehearn, C; Gupta, S; Mansfield, D

2000-01-01

BACKGROUND/AIMS—Familial exudative vitreoretinopathy (FEVR) is associated with mutations in the Norrie disease gene in X linked pedigrees and with linkage to the EVR1 locus at 11q13 in autosomal dominant cases. A large autosomal dominant FEVR family was studied, both clinically and by linkage analysis, to determine whether it differed from the known forms of FEVR.
METHODS—Affected members and obligate gene carriers from this family were examined by slit lamp biomicroscopy, indirect ophthalmos...

Linkage and candidate gene analysis of X-linked familial exudative vitreoretinopathy.

Science.gov (United States)

Shastry, B S; Hejtmancik, J F; Plager, D A; Hartzer, M K; Trese, M T

1995-05-20

Familial exudative vitreoretinopathy (FEVR) is a hereditary eye disorder characterized by avascularity of the peripheral retina, retinal exudates, tractional detachment, and retinal folds. The disorder is most commonly transmitted as an autosomal dominant trait, but X-linked transmission also occurs. To initiate the process of identifying the gene responsible for the X-linked disorder, linkage analysis has been performed with three previously unreported three- or four-generation families. Two-point analysis showed linkage to MAOA (Zmax = 2.1, theta max = 0) and DXS228 (Zmax = 0.5, theta max = 0.11), and this was further confirmed by multipoint analysis with these same markers (Zmax = 2.81 at MAOA), which both lie near the gene causing Norrie disease. Molecular genetic analysis further reveals a missense mutation (R121W) in the third exon of the Norrie's disease gene that perfectly cosegregates with the disease through three generations in one family. This mutation was not detected in the unaffected family members and six normal unrelated controls, suggesting that it is likely to be the pathogenic mutation. Additionally, a polymorphic missense mutation (H127R) was detected in a severely affected patient.

Benign Proliferative Breast Lesions and Risk of Cancer

Directory of Open Access Journals (Sweden)

Serap Erel

2010-06-01

Full Text Available Benign breast lesions (BBL includes a wide variety of histologic entities, which have been broadly classified into non-proliferative lesions, proliferative lesions without atypia, and hyperplasia with atypia. With the increased use of mammography, more benign lesions are being detected, and in order to estimate the risk of breast cancer for specific histologic categories is of great importance to guide clinical management. Women with proliferative lesions without atypia are at slightly increased risk of subsequent breast cancer, whereas women with proliferative lesions with atypia have a higher risk. The risk is 1.5- 2-fold in women with proliferative lesions without atypia, 4-5-fold in women with proliferative lesions with atypia, and 8-10 fold in women with ductal carcinoma in situ. Age at diagnosis of BBL, menopausal status, family history of breast cancer in a first-degree relative, and time since BBL diagnosis on risk of breast cancer are important for risk evaluation. [Archives Medical Review Journal 2010; 19(3.000: 155-167

Pediatric retinal detachment in the Eastern Province of Saudi Arabia: experience of a tertiary care hospital.

Science.gov (United States)

Cheema, Rizwan A; Al-Khars, Wajeeha; Al-Askar, Essam; Amin, Yasir M

2009-01-01

Because no previous studies have addressed the issue, we describe clinical characteristics and surgical outcome of patients with rhegmatogenous retinal detachment (RRD) in a pediatric population of the Eastern province of Saudi Arabia. We conducted a retrospective review of all consecutive cases of pediatric RRD (0-18 years) patients presenting at Dhahran Eye Specialist Hospital, a tertiary care hospital, in the Eastern Province of Saudi Arabia over a period of 3 years. Twenty patients were included in the study, accounting for 9.4% of all retinal detachment surgery cases performed over a period of 3 years (January 2006 to December 2008). The median age was 11.0 years, (range, birth to 18 years). Trauma, (45%) myopia/vitreoretinal degeneration (10%) and prior ocular surgery (25%) were significant risk factors for RRD. Proliferative vitreoretinopathy (PVR) more than grade C was present in 14/20 (70%) of cases. Most patients (15/20, 75%) were treated with pars plana vitrectomy and placement of an encircling buckle, while silicone oil or gas was used as tamponade in 13/20 (65%) patients. Surgery was successful in 17/20 (85%) cases in achieving retinal re-attachment. Visual acuity improved significantly following surgery (Mean preop 2.146 LogMAR, Mean postop 1.497 LogMAR) ( P= .014). Longer duration of RRD ( P =.007) and macular involvement ( P =.05) were associated with worse anatomical outcomes following surgery. Pediatric RRD in the Eastern province is often associated with predisposing pathology. Surgery is successful in achieving anatomical reattachment of the retina in a majority of cases with improvement of visual acuity.

Proliferative lifespan is conserved after nuclear transfer.

Science.gov (United States)

Clark, A John; Ferrier, Patricia; Aslam, Samena; Burl, Sarah; Denning, Chris; Wylie, Diana; Ross, Arlene; de Sousa, Paul; Wilmut, Ian; Cui, Wei

2003-06-01

Cultured primary cells exhibit a finite proliferative lifespan, termed the Hayflick limit. Cloning by nuclear transfer can reverse this cellular ageing process and can be accomplished with cultured cells nearing senescence. Here we describe nuclear transfer experiments in which donor cell lines at different ages and with different proliferative capacities were used to clone foetuses and animals from which new primary cell lines were generated. The rederived lines had the same proliferative capacity and rate of telomere shortening as the donor cell lines, suggesting that these are innate, genetically determined, properties that are conserved by nuclear transfer.

Value of optical coherence tomography in the detection of macular pathology before the removal of silicone oil

Directory of Open Access Journals (Sweden)

Rashad MA

2016-01-01

Full Text Available Mohammad Ahmad Rashad, Ahmed Abdel Aliem Mohamed, Asmaa Ismail Ahmed Department of Ophthalmology, Faculty of Medicine, Ain Shams University, Cairo, Egypt Purpose: To assess the pathological macular changes with optical coherence tomography (OCT before the removal of silicone oil (SiO in eyes that had undergone pars plana vitrectomy for complicated forms of retinal detachment (RD.Patients and methods: Subjects included 48 patients (51 eyes with complicated RD including proliferative vitreoretinopathy, proliferative diabetic retinopathy, recurrent RD, penetrating trauma, uveitis, giant retinal tears, and macular holes. All the eyes had undergone SiO injection. Furthermore, all eyes had been planned for the removal of SiO 6–12 months after the primary surgery. Finally, all eyes had a fundus examination and OCT examination before the silicone oil removal.Results: OCT findings indicated epiretinal membrane in 41% of the eyes, macular edema in 17%, macular detachment in 13.5%, macular thinning in 13.5%, macular holes in 10%, and subretinal membranes in 2%. Preoperative OCT was normal in only 12% of the eyes, while a clinical fundus examination was normal in 43% (P<0.001. Eyes with normal OCT had significantly better mean logMAR (0.35 than eyes with pathological changes detected through OCT (1.28; P<0.001. Surgical modifications were made during the removal of SiO in 74.5% of the eyes.Conclusion: OCT detected significantly more pathological changes than a clinical fundus examination. This had an impact on both surgical step modification during the removal of SiO and predictability of visual outcome after the removal of SiO. Keywords: optical coherence tomography, silicone oil, pars plana vitrectomy, proliferative vitreoretinopathy, proliferative diabetic retinopathy

Small-Signal Modeling of the PVR-Based AD Scheme and Controller Design for Three-Phase Standalone DG System

DEFF Research Database (Denmark)

Shen, Pan; Han, Yang; Lu, Chang

2016-01-01

This paper presents the small-signal state-space modeling and a new multifunctional multi-loop control strategy for three-phase inverter-based islanded DG systems under unbalanced and/or nonlinear load conditions. The proposed control methodology utilizes the parallel virtual resistance (PVR...... controllers are based on an enhanced proportional resonant (PR) structure to achieve zero steady-state error, and multi-resonant harmonic compensator (MRHC) plus PR controller to prevent low-order load current harmonics to distort the output voltage. The proposed small-signal model of the islanded DG system...... with multi-loop control strategy in the stationary reference frame is presented. Moreover, an enhanced delay compensation (EDC) scheme based on two integrators of the discrete PR controller is presented to improve stability margins with a higher accuracy compared with the existing methods. Then, a detailed...

Lifespan extension by preserving proliferative homeostasis in Drosophila.

Directory of Open Access Journals (Sweden)

Benoît Biteau

2010-10-01

Full Text Available Regenerative processes are critical to maintain tissue homeostasis in high-turnover tissues. At the same time, proliferation of stem and progenitor cells has to be carefully controlled to prevent hyper-proliferative diseases. Mechanisms that ensure this balance, thus promoting proliferative homeostasis, are expected to be critical for longevity in metazoans. The intestinal epithelium of Drosophila provides an accessible model in which to test this prediction. In aging flies, the intestinal epithelium degenerates due to over-proliferation of intestinal stem cells (ISCs and mis-differentiation of ISC daughter cells, resulting in intestinal dysplasia. Here we show that conditions that impair tissue renewal lead to lifespan shortening, whereas genetic manipulations that improve proliferative homeostasis extend lifespan. These include reduced Insulin/IGF or Jun-N-terminal Kinase (JNK signaling activities, as well as over-expression of stress-protective genes in somatic stem cell lineages. Interestingly, proliferative activity in aging intestinal epithelia correlates with longevity over a range of genotypes, with maximal lifespan when intestinal proliferation is reduced but not completely inhibited. Our results highlight the importance of the balance between regenerative processes and strategies to prevent hyperproliferative disorders and demonstrate that promoting proliferative homeostasis in aging metazoans is a viable strategy to extend lifespan.

Surgical challenges and outcomes of rhegmatogenous retinal detachment in albinism.

Science.gov (United States)

Sinha, M K; Chhablani, J; Shah, B S; Narayanan, R; Jalali, S

2016-03-01

To report the outcomes and surgical difficulties during rhegmatogenous retinal detachment (RRD) repair in patients with albinism. Retrospective analysis of 10 eyes of 9 patients with albinism that underwent RRD repair was performed. Collected data included demographic details, preoperative examination details, surgical procedure, surgical difficulties, anatomical, and visual outcomes. Outcome measures were retinal reattachment and visual acuity at the last follow-up. Mean preoperative best-corrected visual acuity (BCVA) was logMAR (Logarithm of the Minimum Angle of Resolution) 2.15 (range 0.9-3.0) with preoperative localization of causative break in six eyes. One eye had proliferative vitreoretinopathy grade C1 preoperatively. Four eyes underwent scleral buckling (SB) and six underwent 20G pars plana vitrectomy (PPV) with silicone oil injection. Intraoperative complication as iatrogenic retinal break occurred in four eyes. For retinopexy during vitrectomy, endolaser delivery was possible in three out of six eyes, whereas three eyes had cryopexy. The mean follow-up was 12 months in SB group (range 1-12; median 12 months) and 5.33 months (range 1-12; median 3 months) in PPV group. Among vitrectomized eye, two eyes had recurrence at 3 months with oil in situ. Rest of the eyes had attached retina at last follow-up. Mean BCVA at last follow-up was logMAR -1.46 (range 0.7-2.0) with mean improvement of -0.57 logMAR. Identification of break, induction of posterior vitreous detachment, and endolaser delivery may be difficult during RRD repair in patients with albinism. The incidence of PVR appeared less in these eyes. Both SB and PPV were efficacious and appear to be good surgical techniques for use in this patient population.

Predictive factors for postoperative visual function of primary chronic rhegmatogenous retinal detachment after scleral buckling.

Science.gov (United States)

Fang, Wei; Li, Jiu-Ke; Jin, Xiao-Hong; Dai, Yuan-Min; Li, Yu-Min

2016-01-01

To evaluate predictive factors for postoperative visual function of primary chronic rhegmatgenous retinal detachment (RRD) after sclera buckling (SB). Totally 48 patients (51 eyes) with primary chronic RRD were included in this prospective interventional clinical cases study, which underwent SB alone from June 2008 to December 2014. Age, sex, symptoms duration, detached extension, retinal hole position, size, type, fovea on/off, proliferative vitreoretinopathy (PVR), posterior vitreous detachment (PVD), baseline best corrected visual acuity (BCVA), operative duration, follow up duration, final BCVA were measured. Pearson correlation analysis, Spearman correlation analysis and multivariate linear stepwise regression were used to confirm predictive factors for better final visual acuity. Student's t-test, Wilcoxon two-sample test, Chi-square test and logistic stepwise regression were used to confirm predictive factors for better vision improvement. Baseline BCVA was 0.8313±0.6911 logMAR and final BCVA was 0.4761±0.4956 logMAR. Primary surgical success rate was 92.16% (47/51). Correlation analyses revealed shorter symptoms duration (r=0.3850, P=0.0053), less detached area (r=0.5489, Ppredictive factors were better baseline BCVA [partial R-square (PR(2))=0.5316, Ppredictive factors for better vision improvement were better baseline vision [odds ratio (OR) =50.369, P=0.0041] and longer follow up duration (OR=1.144, P=0.0067). Independent predictive factors for better visual outcome of primary chronic RRD after SB are better baseline BCVA, shorter symptoms duration, shorter operative duration and longer follow up duration, while independent predictive factors for better vision improvement after operation are better baseline vision and longer follow up duration.

DIAGNOSTIC CRITERIA FOR PROLIFERATIVE THYROID LESIONS IN BONY FISHES

Science.gov (United States)

Thyroid proliferative lesions are rather common in bony fishes but disagreement exists in the fish pathology community concerning diagnostic criteria for hyperplastic versus neoplastic lesions. To simplify the diagnosis of proliferative thyroid lesions and to reduce confusion reg...

Proliferative and non-proliferative lesions of the rat and mouse integument.

Science.gov (United States)

Mecklenburg, Lars; Kusewitt, Donna; Kolly, Carine; Treumann, Silke; Adams, E Terence; Diegel, Kelly; Yamate, Jyoji; Kaufmann, Wolfgang; Müller, Susanne; Danilenko, Dimitry; Bradley, Alys

2013-01-01

The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) project is a joint initiative of the societies of toxicological pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP) and North America (STP). Its aim is to develop an internationally-accepted nomenclature for proliferative and non-proliferative lesions in laboratory rodents. A widely accepted international harmonization of nomenclature in laboratory animals will decrease confusion among regulatory and scientific research organizations in different countries and will provide a common language to increase and enrich international exchanges of information among toxicologists and pathologists. The purpose of this publication is to provide a standardized nomenclature for classifying microscopical lesions observed in the integument of laboratory rats and mice. Example colour images are provided for most lesions. The standardized nomenclature presented in this document and additional colour images are also available electronically at http://www.goreni.org. The nomenclature presented herein is based on histopathology databases from government, academia, and industrial laboratories throughout the world, and covers lesions that develop spontaneously as well as those induced by exposure to various test materials. (DOI: 10.1293/tox.26.27S; J Toxicol Pathol 2013; 26: 27S-57S).

Proliferative capacity of murine hematopoietic stem cells

International Nuclear Information System (INIS)

Hellman, S.; Botnick, L.E.; Hannon, E.C.; Vigneulle, R.M.

1978-01-01

The present study demonstrates a decrease in self-renewal capacity with serial transfer of murine hematopoietic stem cells. Production of differentiated cell progeny is maintained longer than stem cell self-renewal. In normal animals the capacity for self-renewal is not decreased with increasing donor age. The stem cell compartment in normal animals, both young and old, appears to be proliferatively quiescent. After apparent recovery from the alkylating agent busulfan, the probability of stem cell self-renewal is decreased, there is a permanent defect in the capacity of the bone marrow for serial transplantation, and the stem cells are proliferatively active. These findings support a model of the hematopoietic stem cell compartment as a continuum of cells with decreasing capacities for self-renewal, increasing likelihood for differentiation, and increasing proliferative activity. Cells progress in the continuum in one direction and such progression is not reversible

Endothelin-1 is associated with fibrosis in proliferative diabetic retinopathy membranes.

Science.gov (United States)

Chang, William; Lajko, Michelle; Fawzi, Amani A

2018-01-01

To characterize the relationship between endothelin-1 and fibrosis in epiretinal membranes in proliferative diabetic retinopathy and explore the role of endothelial-mesenchymal transition in these membranes. Membranes were obtained from eyes undergoing pars plana vitrectomy for complicated proliferative diabetic retinopathy or idiopathic epiretinal membrane. Through standard immunohistochemical techniques, we labeled membranes to explore the distribution of endothelin-1 and endothelin receptor B, comparing proliferative diabetic retinopathy and idiopathic epiretinal membranes. In addition, membranes were also labeled with markers for fibroblasts, endothelial, and glial cells and studied with confocal laser scanning microscopy. The intensity of endothelin-1 labeling was quantified using standard image analysis software. Fourteen membranes were included in the analysis, nine from eyes with proliferative diabetic retinopathy and five idiopathic membranes. Flatmount diabetic membranes showed co-localization of endothelin-1 with S100A4 and CD31. Immunohistochemistry and quantitative analysis of cross-sectional membranes showed significantly higher endothelin-1 labeling in proliferative diabetic retinopathy membranes compared to idiopathic membranes (pmembranes showed more elements staining positive for S100A4 compared to idiopathic membranes. Epiretinal membrane formation in proliferative diabetic retinopathy involves higher tissue levels of endothelin-1 and fibroblastic activity. Furthermore, endothelin-1, endothelial and fibroblastic staining appear to be correlated, suggestive of endothelial-to-mesenchymal transition in proliferative diabetic retinopathy.

Atypical proliferative myositis: original MR description with pathologic correlation: Case report

Energy Technology Data Exchange (ETDEWEB)

Jarraya, Mohamed; Guermazi, Ali [Boston University School of Medicine, Department of Radiology, Musculoskeletal Section, Boston, MA (United States); Parva, Pedram [VA Boston Healthcare System, Boston, MA (United States); Stone, Michael [Stamford Hospital, Department of Surgery, Stamford, CT (United States); Klein, Michael J. [Hospital for Special Surgery, Department of Pathology and Laboratory Medicine, New York, NY (United States)

2014-08-15

Proliferative myositis (PM) along with proliferative fasciitis and nodular fasciitis are a group of pseudosarcomatous myofibroblastic proliferations. Although the histologic presentation of each is almost identical, the magnetic resonance imaging (MRI) appearance of proliferative myositis is closer to that of inflammatory myopathies. We report a case of PM in which the imaging and histologic features combine typical findings of PM with unusual imaging features, suggesting of reactive (or nodular) fasciitis. (orig.)

Atypical proliferative myositis: original MR description with pathologic correlation: Case report

International Nuclear Information System (INIS)

Jarraya, Mohamed; Guermazi, Ali; Parva, Pedram; Stone, Michael; Klein, Michael J.

2014-01-01

Proliferative myositis (PM) along with proliferative fasciitis and nodular fasciitis are a group of pseudosarcomatous myofibroblastic proliferations. Although the histologic presentation of each is almost identical, the magnetic resonance imaging (MRI) appearance of proliferative myositis is closer to that of inflammatory myopathies. We report a case of PM in which the imaging and histologic features combine typical findings of PM with unusual imaging features, suggesting of reactive (or nodular) fasciitis. (orig.)

Correlation between proliferative activity and cellular thickness of human mesenchymal stem cells

International Nuclear Information System (INIS)

Katsube, Yoshihiro; Hirose, Motohiro; Nakamura, Chikashi; Ohgushi, Hajime

2008-01-01

A cell's shape is known to be related to its proliferative activity. In particular, large and flat mammalian adult stem cells seem to show slow proliferation, however using quantitative analysis to prove the phenomenon is difficult. We measured the proliferation and cellular thickness of human mesenchymal stem cells (MSCs) by atomic force microscopy and found that MSCs with high proliferative activity were thick while those with low proliferative activity were thin, even though these MSCs were early passage cells. Further, low proliferative MSCs contained many senescence-associated β-galactosidase positive cells together with high senescence-associated gene expression. These findings suggest that the measurement of cellular thickness is useful for estimating the proliferative activity of human MSCs and is expected to be a practical tool for MSC applications in regenerative medicine

Perturbed CD8+ T cell TIGIT/CD226/PVR axis despite early initiation of antiretroviral treatment in HIV infected individuals

DEFF Research Database (Denmark)

Tauriainen, Johanna; Scharf, Lydia; Frederiksen, Juliet

2017-01-01

HIV-specific CD8+ T cells demonstrate an exhausted phenotype associated with increased expression of inhibitory receptors, decreased functional capacity, and a skewed transcriptional profile, which are only partially restored by antiretroviral treatment (ART). Expression levels of the inhibitory...... and displayed a diminished expression of CD226. Furthermore, expression of PVR was increased on CD4+ T cells, especially T follicular helper (Tfh) cells, in HIV-infected lymph nodes. These results depict a skewing of the TIGIT/CD226 axis from CD226 co-stimulation towards TIGIT-mediated inhibition of CD8+ T...... increased over time despite early initiation of ART. HIV-specific CD8+ T cells were almost exclusively TIGIT+, had an inverse expression of the transcription factors T-bet and Eomes and co-expressed PD-1, CD160 and 2B4. HIV-specific TIGIThi cells were negatively correlated with polyfunctionality...

Proliferative changes in nonpalpable breast lesions detected by mammography

International Nuclear Information System (INIS)

Vega, A.; Delgado, A.; Ortega, E.; Garijo, F.; Mosquera, J.; Sogo, C.; Alvarez, A.

2000-01-01

To analyze retrospectively the radiological findings in nonpalpable breast lesions detected by mammography that lead to the performance of surgical biopsy, resulting in a histological diagnosis of proliferative breast disease with and without atypia. From two Spanish hospitals, 421 women with 429 biopsies indicative of the presence of proliferative breast disease with and without atypia were selected out of a total of 1252 surgical biopsies in nonpalpable lesions that proved to be benign. Age, personal and familial history of breast cancer, reason for requesting the mammography and radiological findings that had indicated the need for surgical biopsy were recorded for each patient. The diagnosis was proliferative breast disease (epithelial hyperplasia) in 347 women with 354 biopsies and atypical hyperplasia in the remaining 74 women with 75 biopsies, representing 28% and 6%, respectively, of the 1252 biopsies of lesions found to be benign. In 221 of the 354 cases of epithelial hyperplasia (62%) and 45 of the 75 cases of atypical hyperplasia (60%), the presence of calcifications was the most common radiological findings leading to biopsy (p<0.05). Parenchymal distortion, with or without calcifications, was the second most common radiological sign. The histological study revealed a close relationship between these proliferative events and radial scars. Calcifications are the radiological finding that most frequently indicate the need for surgical biopsy in nonpalpable lesions that results in a diagnosis of proliferative breast disease with and without atypia. (Author) 12 refs

Screening for NDP mutations in 44 unrelated patients with familial exudative vitreoretinopathy or Norrie disease.

Science.gov (United States)

Yang, Huiqin; Li, Shiqiang; Xiao, Xueshan; Guo, Xiangming; Zhang, Qingjiong

2012-08-01

To screen mutations in the norrin (NDP) gene in 44 unrelated Chinese patients with familial exudative vitreoretinopathy (FEVR, 38 cases) or Norrie disease (6 cases) and to describe the associated phenotypes. Of the 44 patients, mutation in FZD4, LRP5, and TSPAN12 was excluded in 38 patients with FEVR in previous study. Sanger sequencing was used to analyze the 2 coding exons and their adjacent regions of NDP in the 44 patients. Clinical data were presented for patients with mutation. NDP variants in 5 of the 6 patients with Norrie disease were identified, including a novel missense mutation (c.164G>A, p.Cys55Phe) in one patient, two known missense mutations (c.122G>A, p.Arg41Lys; c.220C>T, p.Arg74Cys) in two patients, and a gross deletion encompassing the two coding exons in two patients. Of the 5 patients, 3 had a family history and 2 were singleton cases. No mutation in NDP was detected in the 38 patients with FEVR. NDP mutations are common cause of Norrie disease but might be rare cause for FEVR in Chinese.

Genotype-Phenotype Characterization of Novel Variants in Six Italian Patients with Familial Exudative Vitreoretinopathy.

Science.gov (United States)

Iarossi, Giancarlo; Bertelli, Matteo; Maltese, Paolo Enrico; Gusson, Elena; Marchini, Giorgio; Bruson, Alice; Benedetti, Sabrina; Volpetti, Sabrina; Catena, Gino; Buzzonetti, Luca; Ziccardi, Lucia

2017-01-01

Familial exudative vitreoretinopathy (FEVR) is a complex disorder characterized by incomplete development of the retinal vasculature. Here, we report the results obtained on the spectrum of genetic variations and correlated phenotypes found in a cohort of Italian FEVR patients. Eight probands (age range 7-19 years) were assessed by genetic analysis and comprehensive age-appropriate ophthalmic examination. Genetic testing investigated the genes most widely associated in literature with FEVR: FZD4 , LRP5 , TSPAN12 , and NDP . Clinical and genetic evaluations were extended to relatives of probands positive to genetic testing. Six out of eight probands (75%) showed a genetic variation probably related to the phenotype. We identified four novel genetic variants, one variant already described in association with Norrie disease and one previously described linked to autosomal dominant FEVR. Pedigree analysis of patients led to the classification of four autosomal dominant cases of FEVR (caused by FZD4 and TSPAN12 variants) and two X-linked FEVR probands ( NDP variants). None of the patients showed variants in the LRP5 gene. This study represents the largest cohort study in Italian FEVR patients. Our findings are in agreement with the previous literature confirming that FEVR is a clinically and genetically heterogeneous retinal disorder, even when it manifests in the same family.

Genotype-Phenotype Characterization of Novel Variants in Six Italian Patients with Familial Exudative Vitreoretinopathy

Directory of Open Access Journals (Sweden)

Giancarlo Iarossi

2017-01-01

Full Text Available Familial exudative vitreoretinopathy (FEVR is a complex disorder characterized by incomplete development of the retinal vasculature. Here, we report the results obtained on the spectrum of genetic variations and correlated phenotypes found in a cohort of Italian FEVR patients. Eight probands (age range 7–19 years were assessed by genetic analysis and comprehensive age-appropriate ophthalmic examination. Genetic testing investigated the genes most widely associated in literature with FEVR: FZD4, LRP5, TSPAN12, and NDP. Clinical and genetic evaluations were extended to relatives of probands positive to genetic testing. Six out of eight probands (75% showed a genetic variation probably related to the phenotype. We identified four novel genetic variants, one variant already described in association with Norrie disease and one previously described linked to autosomal dominant FEVR. Pedigree analysis of patients led to the classification of four autosomal dominant cases of FEVR (caused by FZD4 and TSPAN12 variants and two X-linked FEVR probands (NDP variants. None of the patients showed variants in the LRP5 gene. This study represents the largest cohort study in Italian FEVR patients. Our findings are in agreement with the previous literature confirming that FEVR is a clinically and genetically heterogeneous retinal disorder, even when it manifests in the same family.

Retinal detachment secondary to ocular perforation during retrobulbar Anaesthesia

Directory of Open Access Journals (Sweden)

Gopal Lingam

1995-01-01

Full Text Available The clinical characteristics and the retinal breaks associated with rhegmatogenous retinal detachments secondary to accidental globe perforation during local infiltration anaesthesia in five highly myopic eyes are presented. Retinal detachment was total with variable proliferative vitreoretinopathy. The pattern of retinal breaks was rather typical and predictable. Management involved vitreous surgery with internal tamponade by silicone oil in four eyes and perfluoropropane gas in one eye. At the last follow-up, all eyes had attached retina. One eye did not recover useful vision due to possible concurrent optic nerve damage.

Proliferative and inflammatory factors in the vitreous of patients with proliferative diabetic retinopathy

Directory of Open Access Journals (Sweden)

V V Chernykh

2015-01-01

Full Text Available Purpose: The purpose was to measure the concentrations of various cytokines and growth factors (including vascular endothelial growth factor [VEGF] and pigment epithelium-derived factor [PEDF] in the vitreous of patients with proliferative diabetic retinopathy (PDR and to investigate interaction between inflammatory and proliferative factors in the genesis of PDR. Materials and Methods : Vitreous samples from 32 eyes with PDR and 25 eyes without diabetes mellitus and signs of DR (control were collected. Vitreous concentrations of VEGF, PEDF, monocyte chemotactic protein-1 (MCP-1, interleukin-4 (IL-4, IL-6, IL-8, IL-10, IL-17A, and secretory immunoglobulin A (sIgA were simultaneously measured using enzyme-linked immunoassay. Results : Vitreous levels of VEGF, PEDF, IL-17A, IL-6, IL-8, IL-4, and sIgA were significantly (Π < 0.05 higher in eyes with PDR compared to control. The concentration of VEGF was more than 17-times higher than in control, and the concentration of PEDF was not changed oppositely and was also higher (1.45-times compared to control, that may indicate disturbances of compensatory mechanisms in angiogenesis regulation in PDR. Significant (Π < 0.05 positive correlations were observed between vitreous concentrations of VEGF and IL-17ΐ (r = 0.45, VEGF and IL-8 (r = 0.48, VEGF and IL-4 (r = 0.51, PEDF and IL-17ΐ (r = 0.48, PEDF and IL-8 (r = 0.59, MCP-1 and PEDF (r = 0.72, MCP-1 and IL-8 (r0 = 0.45, IL-4 and IL-17ΐ (r = 0.65, IL-4 and IL-8 (r = 0.71, IL-8 and IL-17ΐ (r = 0.59. Conclusions: Significantly raised levels of inflammatory and proliferative factors and numerous positive correlations between them may demonstrate a significant role of activation of vascular proliferation and local inflammation in the pathogenesis of PDR.

Bilateral proliferative retinopathy in B-cell acute lymphoblastic leukemia

Directory of Open Access Journals (Sweden)

Devesh Kumawat

2018-01-01

Full Text Available A 4-year-old child with B-cell acute lymphoblastic leukemia presented with vitreous hemorrhage due to proliferative retinopathy in both eyes. Pars plana vitrectomy was performed in both eyes to clear nonresolving vitreous hemorrhage after systemic stabilization. Visual recovery was limited by the disc drag in the right eye and subfoveal exudation in the left eye. Etiopathogenesis and management of proliferative retinopathy in acute leukemias are discussed.

[Stickler's syndrome (dystrophia vitreoretinalis hereditaria). Results of surgery for retinal detachment].

Science.gov (United States)

Karel, I; Dolezalová, J; Oudová, P

2001-05-01

Stickler's syndrome (SS) is an autosomal dominant hereditary disease of the collagenous connective tissue where impaired development of the vitreous body gel and peripheral retina and detachment of the retina are associated with general manifestations. The objective of the retrospective study was to evaluate the long-term results of surgery of retinal detachment in SS. The group of patients comprised 7 patients, 6 men and 1 woman aged 4 to 45 years, average age 16.8 years. Autosomal dominant heredity was obvious in 6 members (85.7%) of two families. General manifestations of SS included abnormalities of the facial skeleton (6 patients), cleft palate (4 patients), impaired hearing (2 patients), marfanoid habitus (2 patients) and hyperextensibility of the joints (4 patients). In the eyes with SS was manifested by myopia from -1 to -9 D and a liquid vitreous body. Multiple foci of lattice degeneration supplemented the finding in 6 patients (85.7%). Detachment of the retina was a manifestation of SS in 12 of 14 eyes (85.7%). It was manifested in 5 of 7 patients concurrently or within 12 years in both eyes. The causes of retinal detachment were multiple equatorial and postequatorial tears due to lattice degeneration in 8 eyes (66.7%) or a giant tear in 4 eyes (33.3%). Advanced proliferative vitreoretinopathy (PVR) was associated with retinal detachment in 8 eyes (66.7%) and in 6 eyes (50%) it was not possible to assess the beginning of retinal detachment. In 3 of 5 patients with bilateral retinal detachment the adverse course of retinal detachment on the first eye was followed 8 to 12 years previously in another department: two retinal detachments with giant tears were evaluated as inoperable and one inveterated detachment with advanced PVR was operated unsuccessfully. Retinal detachment was operated in 9 eyes of 7 patients, in two patients both eyes were operated simultaneously. The patients were followed up after surgery for 11 months to 15 years, on average for 65

Mutations in the NDP gene: contribution to Norrie disease, familial exudative vitreoretinopathy and retinopathy of prematurity.

Science.gov (United States)

Dickinson, Joanne L; Sale, Michèle M; Passmore, Abraham; FitzGerald, Liesel M; Wheatley, Catherine M; Burdon, Kathryn P; Craig, Jamie E; Tengtrisorn, Supaporn; Carden, Susan M; Maclean, Hector; Mackey, David A

2006-01-01

To examine the contribution of mutations within the Norrie disease (NDP) gene to the clinically similar retinal diseases Norrie disease, X-linked familial exudative vitreoretinopathy (FEVR), Coat's disease and retinopathy of prematurity (ROP). A dataset comprising 13 Norrie-FEVR, one Coat's disease, 31 ROP patients and 90 ex-premature babies of Norrie disease patients. Furthermore, a previously described 14-bp deletion located in the 5' unstranslated region of the NDP gene was detected in three cases of regressed ROP. A second heterozygotic 14-bp deletion was detected in an unaffected ex-premature girl. Only two of the 13 Norrie-FEVR index cases had the full features of Norrie disease with deafness and mental retardation. Two novel mutations within the coding region of the NDP gene were found, one associated with a severe disease phenotypes of Norrie disease and the other with FEVR. A deletion within the non-coding region was associated with only mild-regressed ROP, despite the presence of low birthweight, prematurity and exposure to oxygen. In full-term children with retinal detachment only 15% appear to have the full features of Norrie disease and this is important for counselling parents on the possible long-term outcome.

Disease: H00589 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available H00589 Familial exudative vitreoretinopathy (FEVR), including: Exudative vitreoretinopathy... 1 (EVR1); Exudative vitreoretinopathy2, X-linked ... (EVR2); Exudative vitreoretinopathy 4 (EVR4); Exudative vitreoretinopathy... 5 (EVR5); Norrie disease (ND) Familial exudative vitreoretinopathy (FEVR) and Norri...RP5 [HSA:4041] [KO:K03068] (EVR5) TSPAN12 [HSA:23554] [KO:K17355] ... Exudative vitreoretinopathy 3 (EVR3) ...ion spectrum in familial exudative vitreoretinopathy and Norrie disease with iden

Standard effective doses for proliferative tumours

International Nuclear Information System (INIS)

Jones, L.C.; Hoban, P.

1999-01-01

This study was undertaken to investigate the treatment schedules used clinically for highly proliferative tumours, particularly with reference to the effects of fraction size, fraction number and treatment duration. The linear quadratic model (with time component) is used here to compare non-standard treatment regimens (e.g. accelerated and hyperfractionated schedules), currently the focus of randomized trials, with each other and some common 'standard regimens'. To ensure easy interpretation of results, two parameters known as proliferative standard effective dose one (PSED 1 ) and proliferative standard effective dose two (PSED 2 ) have been calculated for each regimen. Graphs of PSED 1 and PSED 2 versus potential doubling time (T p ) have been generated for a range of fractionation regimens which are currently under trial in various randomized studies. From these graphs it can be seen that the highly accelerated schedules (such as CHART) only show advantages for tumours with very short potential doubling times. Calculations for most of the schedules considered showed at least equivalent tumour control expected for the trial schedule compared with the control arm used and these values agree quite well with clinical results. These calculations are in good agreement with clinical results available at present. The greater the PSED 1 or PSED 2 for the schedule considered the greater the tumour control, which can be expected. However, as has been seen with clinical trials, this higher cell kill also results in higher acute effects which have proved too great for some accelerated schedules to continue. (author)

Proliferative glomerulonephritis and primary antiphospholipid syndrome

International Nuclear Information System (INIS)

Abdalla, H. Abdalla; Kfoury, Hala K.; Al-Khader, Abdulla A.; Al-Suleiman, M.

2006-01-01

Little is known regarding the association of primary antiphospholipid syndrome (APLS) and proliferative glomerulonephiritis (GN). We describe a biopsy-documented case with primary APLS and proliferative (GN) with no evidence of thrombotic microangiopathy (TMA), and in the absence of other manifestations of systematic lupus erythematosus (SLE). She presented initially with left popliteal deep venous thrombosis and nephrotic syndrome. Her first pregnancy at the age of 26 years resulted in the intra-uterine fetal death at term. Two subsequent pregnancies ended up with miscarriages at 3 and 4 months of gestation. Urinalysis revealed glomerular red blood cells of 1.0000.000/ml and granular cast; proteinuria of 13.4grams/24 hours, which was non-selective; hemoglobin 12 gm/dl, normal white blood cell and platelets; serum albumin 2.6gm/dl; anti-nuclear antibody (ANA) and anti DNA were negative and complement levels normal. Lupus anticoagulant was positive leading to a diagnosis of primary APLS. The biopsy findings were consistent with membranoproliferative GN. She continued to have steroid-resistant proteinuria, but stable renal function after a 12-year follow up period. She had 2 pregnancies during this period and was delivered at term using caesarian section. She received heparin during the pregnancies. Later she developed hypertension easily controlled by atenolol. This case provides evidence that primary APLS can be associated with proliferative GN due to immune deposits and not only TMA as previously reported, and in the complete absence of SLE. Performing more renal biopsies in this group of patients may disclose a greater prevalence of proleferative GN and may help in devising a rationale for treatment. (author)

The Relationship between Proliferative Scars and Endothelial Function in Surgically Revascularized Patients

Directory of Open Access Journals (Sweden)

Murat Ziyrek

2015-12-01

Full Text Available Background: Proliferative scars are benign fibrotic proliferations which demonstrate abnormal wound healing in response to skin injuries. As postulated in the “response to injury hypothesis”, atherosclerosis is also triggered by an endothelial injury. Keloid and atherosclerotic processes have many pathophysiological and cytological features in common. Aims: In this study, we investigated the relationship between proliferative scars and endothelial function in surgically revascularized patients. We aimed to test the hypothesis that atherosclerosis is a wound healing abnormality. Study Design: Cross-sectional study. Methods: Consecutive patients who were admitted to the cardiology outpatient clinic with a history of coronary artery bypass grafting operation were evaluated. Thirty-three patients with proliferative scars at the median sternotomy site formed the keloid group, and 36 age- and sex-matched patients with no proliferative scar at the median sternotomy site formed the control group. Endothelial function was evaluated by flow-mediated vasodilatation of the brachial artery via ultrasonograhic examination. Results: There is no signicant difference according to the demographic data, biochemical parameters, clinical parameters and number of grafts between keloid and control groups. Endothelial-dependent vasodilatory response was lower in the keloid group than the control group (9.30±3.5 and 18.68±8.2, respectively; p=0.001. Conclusion: This study showed that endothalial dysfunction, which is strongly correlated with atherosclerosis, was more prominent in patients with proliferative scars. As proliferative scars and atherosclerosis have many features in common, we might conclude that atherosclerosis is a wound healing abnormality.

PROSPECTIVE STUDY OF HISTOLOGICAL PROLIFERATIVE CHANGES IN ADJACENT AREAS OF BREAST CANCER

Directory of Open Access Journals (Sweden)

Rema Nair Sarkar

2016-11-01

Full Text Available BACKGROUND Breast cancer remains a global health problem with an increasing incidence. Proliferative breast diseases are recognised as one of the risk factors in the development of carcinoma. This study was undertaken to know the frequency of proliferative lesions and other lesions in association with breast carcinomas in mastectomy specimens. MATERIALS AND METHODS 100 cases of excised carcinoma breast sent to the Department of Pathology for a three-year period at tertiary care centre was thoroughly examined and changes adjacent to the tumour was recorded and tissue was subjected for histopathological examination and results tabulated. RESULTS Infiltrating duct cell carcinoma, Not Otherwise Specified (NOS type was present in 89% of cases. Among the associated lesions, nonproliferative lesions constituted 16%, proliferative breast disease without atypia 29%, proliferative breast disease with atypia 10% and others 45%. Fibrocystic disease constituted 14% of cases, epithelial hyperplasia 15%, sclerosing adenosis 12% and atypical ductal hyperplasia in 10% of cases. Other types of associated lesions were duct carcinoma in situ in 4 cases. CONCLUSION Proliferative lesions adjacent to carcinoma breast were seen in 39% of cases. Fibrocystic disease, epithelial hyperplasia, sclerosing adenosis and atypical ductal hyperplasia being the commonest lesions adjacent to carcinoma breast in the present study.

The use of analogy in pro-life argumentation

Directory of Open Access Journals (Sweden)

Simona Mazilu

2012-11-01

Full Text Available The paper is concerned with how analogy is strategically used in pro-life argumentation on abortion. Pragma-dialectics (van Eemeren and Grootendorst 1992 offers a set of critical questions by means of which I will evaluate the use of the argumentation based on a relation of analogy in terms of dialectical soundness. Examining various pro-life texts, I have noticed that the analogies employed remain unexplained. Therefore, despite the apparent similarities between abortion and the German holocaust or slavery, for instance, there are essential differences which are not mentioned. I claim that these analogies mainly have a rhetorical function, to operate what has been called by Micheli (2007: 960 “a transfer of emotional consensus”.

A novel missense mutation of NDP in a Chinese family with X-linked familial exudative vitreoretinopathy.

Science.gov (United States)

Liu, Hong Yan; Huang, Jia; Wang, Rui Li; Wang, Yue; Guo, Liang Jie; Li, Tao; Wu, Dong; Wang, Hong Dan; Guo, Qian Nan; Dong, Dao Quan

2016-11-01

Familial exudative vitreoretinopathy (FEVR) is a hereditary ocular disorder characterized by a failure of peripheral retinal vascularization. In this report, we describe a novel missense mutation of the Norrie disease gene (NDP) in a Chinese family with X-linked FEVR. Ophthalmologic evaluation was performed on four male patients and seven unaffected individuals after informed consent was obtained. Venous blood was collected from the 11 members of this family, and genomic DNA was extracted using standard methods. The coding exons 2 and 3 and their corresponding exon-intron junctions of NDP were amplified by polymerase chain reaction and then subjected to direct DNA sequencing. A novel missense mutation (c.310A>C) in exon 3, leading to a lysine-to-glutamine substitution at position 104 (p.Lys104Gln), was identified in all four patients with X-linked FEVR. Three unaffected female individuals (III2, IV3, and IV11) were found to be carriers of the mutation. This mutation was not detected in other unaffected individuals. The mutation c.310A>C (p.Lys104Gln) in exon 3 of NDP is associated with FEVR in the studied family. This result further enriches the mutation spectrum of FEVR. Copyright © 2016. Published by Elsevier Taiwan LLC.

A novel missense mutation of NDP in a Chinese family with X-linked familial exudative vitreoretinopathy

Directory of Open Access Journals (Sweden)

Hong Yan Liu

2016-11-01

Full Text Available Familial exudative vitreoretinopathy (FEVR is a hereditary ocular disorder characterized by a failure of peripheral retinal vascularization. In this report, we describe a novel missense mutation of the Norrie disease gene (NDP in a Chinese family with X-linked FEVR. Ophthalmologic evaluation was performed on four male patients and seven unaffected individuals after informed consent was obtained. Venous blood was collected from the 11 members of this family, and genomic DNA was extracted using standard methods. The coding exons 2 and 3 and their corresponding exon–intron junctions of NDP were amplified by polymerase chain reaction and then subjected to direct DNA sequencing. A novel missense mutation (c.310A>C in exon 3, leading to a lysine-to-glutamine substitution at position 104 (p.Lys104Gln, was identified in all four patients with X-linked FEVR. Three unaffected female individuals (III2, IV3, and IV11 were found to be carriers of the mutation. This mutation was not detected in other unaffected individuals. The mutation c.310A>C (p.Lys104Gln in exon 3 of NDP is associated with FEVR in the studied family. This result further enriches the mutation spectrum of FEVR.

Treatment and prevention of porcine proliferative enteropathy with oral tiamulin.

Science.gov (United States)

McOrist, S; Smith, S H; Shearn, M F; Carr, M M; Miller, D J

The effect of an oral treatment or prevention programme, incorporating the antibiotic tiamulin, on the development of proliferative enteropathy in experimentally challenged pigs was studied. Twenty weaner pigs were challenged orally with a virulent inoculum of Lawsonia intracellularis strain LR189/5/83, a British isolate of the causative agent of porcine proliferative enteropathy, and seven control pigs were dosed with a buffer solution. Seven of the 20 challenged pigs were left untreated; they gained less weight than the controls and three of them developed mild to moderate diarrhoea two weeks after the challenge. All seven developed lesions, six visible grossly, of proliferative enteropathy, and numerous intracellular L intracellularis were detected in sections of the intestines examined three weeks after the challenge. To test a 'prevention' dosing strategy for tiamulin, six of the challenged pigs were dosed orally with 50 ppm tiamulin, incorporated in a 2 per cent stabilised premix, given from two days before the challenge until they were euthanased. To test a 'treatment' strategy, the remaining group of seven challenged pigs were dosed orally with 150 ppm tiamulin given in the premix from seven days after challenge until they were euthanased. All the control pigs and the 13 pigs treated with tiamulin, either before or after challenge, remained clinically normal and had no specific lesions of proliferative enteropathy in sections of the intestines examined post mortem.

Estrogen signaling in the proliferative endometrium: implications in endometriosis

Directory of Open Access Journals (Sweden)

Rita de Cássia Pereira da Costa e Silva

2016-02-01

Full Text Available SUMMARY Even though the physiological role of estrogen in the female reproductive cycle and endometrial proliferative phase is well established, the signaling pathways by which estrogen exerts its action in the endometrial tissue are still little known. In this regard, advancements in cell culture techniques and maintenance of endometrial cells in cultures enabled the discovery of new signaling mechanisms activated by estrogen in the normal endometrium and in endometriosis. This review aims to present the recent findings in the genomic and non-genomic estrogen signaling pathways in the proliferative human endometrium specifically associated with the pathogenesis and development of endometriosis.

Proliferative myositis: a case report

International Nuclear Information System (INIS)

Kim, Young Sook; Jeon, Ho Jong

2002-01-01

We report a case of proliferative myositis arising in the pectoralis major muscle of a 59-year-old man who presented with palpable mass. The initial clinical impression was a malignant tumor. Ultrasonography revealed the lesion as a spindle-shaped hypoechoic mass, and MR imaging of the left pectoralis major muscle showed hypointensity at T1-weighted imaging, hyperintensity at T2-weighted imaging, and strong enhancement at contrast-enhanced T1-weighted imaging

Proliferative myositis: a case report

Energy Technology Data Exchange (ETDEWEB)

Kim, Young Sook; Jeon, Ho Jong [Chosun University College of Medicine, Gwangju (Korea, Republic of)

2002-09-01

We report a case of proliferative myositis arising in the pectoralis major muscle of a 59-year-old man who presented with palpable mass. The initial clinical impression was a malignant tumor. Ultrasonography revealed the lesion as a spindle-shaped hypoechoic mass, and MR imaging of the left pectoralis major muscle showed hypointensity at T1-weighted imaging, hyperintensity at T2-weighted imaging, and strong enhancement at contrast-enhanced T1-weighted imaging.

Secondary glaucoma in CAPN5-associated neovascular inflammatory vitreoretinopathy

Directory of Open Access Journals (Sweden)

Cham A

2016-06-01

Full Text Available Abdourahman Cham,1,2 Mayank Bansal,3 Himanshu K Banda,4 Young Kwon,1 Paul S Tlucek,1 Alexander G Bassuk,5 Stephen H Tsang,6,7 Warren M Sobol,8 James C Folk,1 Steven Yeh,4 Vinit B Mahajan1,2 1Department of Ophthalmology and Visual Sciences, 2Omics Laboratory, University of Iowa, Iowa City, IA, USA; 3Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India; 4Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA, 5Department of Pediatrics, University of Iowa, Iowa City, IA, 6Barbara and Donald Jonas Laboratory of Stem Cells and Regenerative Medicine and Bernard and Shirlee Brown Glaucoma Laboratory, Department of Pathology and Cell Biology, Institute of Human Nutrition, College of Physicians and Surgeons, Columbia University, 7Edward S Harkness Eye Institute, New York-Presbyterian Hospital, New York, NY, 8Retina Physicians & Surgeons, Inc., Dayton, OH, USA Objective: The objective of this study was to review the treatment outcomes of patients with secondary glaucoma in cases of autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV, a hereditary autoimmune uveitis due to mutations in CAPN5. Patients and methods: A retrospective, observational case series was assembled from ADNIV patients with secondary glaucoma. The main outcome measures were intraocular pressure (IOP, visual acuity, use of antiglaucoma medications, ocular surgeries, and adverse outcomes. Perimetry and optic disk optical coherence tomography (OCT were also analyzed. Results: Nine eyes of five ADNIV patients with secondary glaucoma were reviewed. Each received a fluocinolone acetonide (FA implant for the management of posterior uveitis. Following implantation, no eyes developed neovascular glaucoma. Five eyes (in patients 1, 2, and 5 required Ahmed glaucoma valve surgery for the management of steroid-responsive glaucoma. Patient 2 also developed angle closure with iris bombe and underwent laser

Proliferative activity as a prognostic factor of a human tumor radiation reactions

International Nuclear Information System (INIS)

Karakulov, R.K.; Pelevina, I.I.

1986-01-01

The following questions are considered: 1) whether cell proliferation initial parameters can serve for predicting the tumor radial reaction; 2) whether proliferative activity change can be a criterion for estimating the treatment efficiency; 3) acquisition of data on biological peculiarities of different types of tumors. Connection between proliferative activity drop and clinical reaction under tumor radiotherapy is ascertained

Evaluation of VEGF gene polymorphisms and proliferative diabetic retinopathy in Mexican population.

Science.gov (United States)

Gonzalez-Salinas, Roberto; Garcia-Gutierrez, Maria C; Garcia-Aguirre, Gerardo; Morales-Canton, Virgilio; Velez-Montoya, Raul; Soberon-Ventura, Vidal R; Gonzalez, Victoria; Lechuga, Rodrigo; Garcia-Solis, Pablo; Garcia-Gutierrez, David G; Garcia-Solis, Marco Vinicio; Saenz de Viteri, Manuel; Solis-S, Juan C

2017-01-01

To assess if the included vascular endothelial growth factor (VEGF) polymorphisms rs3025035, rs3025021 and rs2010963 are associated to proliferative retinopathy in a Mexican population with type 2 diabetes mellitus (T2DM). A case-control study was conducted in adult individuals with T2DM associated to proliferative retinopathy or non-proliferative retinopathy from Oct. 2014 to Jun. 2015 from the Retina Department of the Asociation to Prevent Blindness in Mexico. The selected patients were adults with a diagnosis of T2DM ≥5y. All subjects had a comprehensive ocular examination and the classification of the retinopathy severity was made considering the Early Treatment Diabetic Retinopathy Study (ETDRS) standardization protocols. Genomic DNA was extracted from whole fresh blood. All samples were genotyped by qPCR for selected VEGF polymorphisms. Hardy-Weinberg equilibrium was calculated by comparing Chi-square values between the expected and the observed values for genotype counts. In total 142 individuals were enrolled, 71 individuals with T2DM and associated proliferative retinopathy and 71 individuals with non-proliferative retinopathy. One-sided Fisher's exact test was performed for rs3025021 [OR (95% CI)=0.44(0.08-2.2); P =0.25] and rs2010963 [OR (95% CI)=0.63(0.25-1.6); P =0.23]. The minor allelic frequencies obtained were 26% for rs3025021, 10% for rs3025035 and 61% for rs2010963. The pairwise linkage disequilibrium between the three SNP was assessed, and was as follows: rs3025021 vs rs3025035: D'=1.0, r 2 =0.1043, P ≤0.0001; rs3025021 vs rs2010963: D'=0.442, r 2 =0.0446, P =0.149; rs3025035 vs rs2010963: D'=0.505, r 2 =0.0214, P =0.142. This is the first analysis involving VEGF polymorphisms and proliferative diabetic retinopathy in a Mexican population. A major finding of the present study is that none of the polymorphisms studied was significantly associated with proliferative retinopathy. Based on these results, we can infer that different populations

3,3'-Diindolylmethane, a cruciferous vegetable derived synthetic anti-proliferative compound in thyroid disease

International Nuclear Information System (INIS)

Tadi, Kiranmayi; Chang Yushan; Ashok, Badithe T.; Chen, Yuangen; Moscatello, Augustine; Schaefer, Steven D.; Schantz, Stimsom P.; Policastro, Anthony J.; Geliebter, Jan; Tiwari, Raj K.

2005-01-01

Considerable epidemiological evidence exists to link thyroid disease with differing patterns of dietary consumption, in particular, cruciferous vegetables. We have been studying the anti-thyroid cancer (TCa) activity of indole-3-carbinol (I3C) found in cruciferous vegetables and its acid catalyzed dimer, 3,3'-diindolylmethane (DIM). There are no studies as yet to elucidate the effect of these compounds on the altered proliferative patterns in goiter or thyroid neoplasia. In this study, we tested the anti-proliferative effects of I3C and DIM on four different thyroid cancer cell lines representative of papillary (B-CPAP and 8505-C) and follicular carcinoma of the thyroid (CGTH-W-1 and ML-1), and primary human goiter cells. Cell survival and IC 50 values for I3C and DIM were calculated by the XTT assay and cell cycle distribution analysis was done by flow cytometry. DIM was found to be a better anti-proliferative agent than I3C in both papillary and follicular TCa resulting in a greater cytotoxic effect at a concentration over three fold lower than predicted by the molar ratio of DIM and I3C. The anti-proliferative activity of DIM in follicular TCa was mediated by a G1 arrest followed by induction of apoptosis. DIM also inhibited the growth of primary goiter cells by 70% compared to untreated controls. Contrary to traditional belief that cruciferous vegetables are 'goitrogenic,' DIM has anti-proliferative effects in glandular thyroid proliferative disease. Our preclinical studies provide a strong rationale for the clinical exploration of DIM as an adjuvant to surgery in thyroid proliferative disease

Norrie disease and exudative vitreoretinopathy in families with affected female carriers.

Science.gov (United States)

Shastry, B S; Hiraoka, M; Trese, D C; Trese, M T

1999-01-01

Norrie disease (ND) is a rare X-linked recessive disorder characterized by congenital blindness, which is often associated with sensorineural hearing loss and mental retardation. X-linked familial exudative vitreoretinopathy (FEVR) is a hereditary disorder characterized by an abnormality of the peripheral retina and is not associated with systemic diseases. X-linked recessive disorders generally do not affect females. Here we show that female carriers can be associated with manifestation of an X-linked disorder. A four-generation family with an affected female, and a history of congenital blindness and hearing loss, was identified through the pro-band. A second family, with a full-term female infant, was evaluated through ophthalmic examinations and found to exhibit ocular features, such as retinal folds, retinal detachment and peripheral exudates. Peripheral blood specimens were collected from several affected and unaffected family members. DNA was extracted and analyzed by single-strand conformation polymorphism (SSCP) following polymerase chain reaction (PCR) amplification of the exons of the Norrie disease gene. The amplified products were sequenced by the dideoxy chain termination method. In an X-linked four-generation family, a novel missense (A118D) mutation in the third exon of the Norrie disease gene, was identified. The mutation was transmitted through three generations and cosegregated with the disease. The affected maternal grandmother and the unaffected mother carried the same mutation in one of their alleles. In an unrelated sporadic family, a heterozygous missense mutation (C96Y) was identified in the third exon of the Norrie disease gene in an affected individual. Analysis of exon-1 and 2 of the Norrie disease gene did not reveal any additional sequence alterations in these families. The mutations were not detected in the unaffected family members and the 116 normal unrelated controls, suggesting that they are likely to be the pathogenic mutations

Proliferative diabetic retinopathy is associated with microalbuminuria in patients with type 2 diabetes

Directory of Open Access Journals (Sweden)

M.C. Boelter

2006-08-01

Full Text Available Diabetic retinopathy is one of the leading causes of blindness in working-age individuals. Diabetic patients with proteinuria or those on dialysis usually present severe forms of diabetic retinopathy, but the association of diabetic retinopathy with early stages of diabetic nephropathy has not been entirely established. A cross-sectional study was conducted on 1214 type 2 diabetic patients to determine whether microalbuminuria is associated with proliferative diabetic retinopathy in these patients. Patients were evaluated by direct and indirect ophthalmoscopy and grouped according to the presence or absence of proliferative diabetic retinopathy. The agreement of diabetic retinopathy classification performed by ophthalmoscopy and by stereoscopic color fundus photographs was 95.1% (kappa = 0.735; P < 0.001. Demographic information, smoking history, anthropometric and blood pressure measurements, glycemic and lipid profile, and urinary albumin were evaluated. On multiple regression analysis, diabetic nephropathy (OR = 5.18, 95% CI = 2.91-9.22, P < 0.001, insulin use (OR = 2.52, 95% CI = 1.47-4.31, P = 0.001 and diabetes duration (OR = 1.04, 95% CI = 1.01-1.07, P = 0.011 were positively associated with proliferative diabetic retinopathy, and body mass index (OR = 0.90, 95% CI = 0.86-0.96, P < 0.001 was negatively associated with it. When patients with macroalbuminuria and on dialysis were excluded, microalbuminuria (OR = 3.3, 95% CI = 1.56-6.98, P = 0.002 remained associated with proliferative diabetic retinopathy. Therefore, type 2 diabetic patients with proliferative diabetic retinopathy more often presented renal involvement, including urinary albumin excretion within the microalbuminuria range. Therefore, all patients with proliferative diabetic retinopathy should undergo an evaluation of renal function including urinary albumin measurements.

Rhegmatogenous retinal detachments associated to Stickler syndrome in a tertiary eye care center in Saudi Arabia

Directory of Open Access Journals (Sweden)

Alshahrani ST

2015-12-01

Full Text Available Saeed T Alshahrani,1 Nicola G Ghazi,2 Saba Al-Rashaed2 1Ophthalmology Department, King Fahad Specialist Hospital, Dammam, 2Vitreoretinal Department, King Khaled Eye Specialist Hospital, Riyadh, Kingdom of Saudi Arabia Purpose: To investigate the clinical findings and outcomes of rhegmatogenous retinal detachment (RRD in Stickler syndrome on affected and fellow eyes that underwent prophylactic retinopexy.Patients and methods: Chart review of 70 eyes (62 patients. Incidence of RRD, postoperative visual acuity, and risk factors were evaluated.Results: Twenty-two patients (35% had RRD in the fellow eye, 37% of the eyes had cataract, 93% had macular detachment, 50% had proliferative vitreoretinopathy, and 41% had posterior vitreous detachment. Success rates were: 60% of patients after scleral buckling; 57.1% after pars plana vitrectomy; and 75% after combined scleral buckling and pars plana vitrectomy. Sixty-one (93.8% of patients had successful surgery (including second surgery. Silicone oil tamponade was significantly associated with final anatomic outcome, with a protective odds ratio of 0.11 (P=0.027. Visual acuity improved in 54% of eyes and decreased in 5%. Statistically significant associations were present for eyes with final visual acuity ≥20/200, and total retinal detachment (P<0.001; preoperative cataract (P=0.023; and proliferative vitreoretinopathy (P<0.001. RRD developed in 16/44 eyes despite laser prophylaxis.Conclusion: Prophylactic retinopexy was not beneficial for Stickler syndrome patients. Success of primary surgery for RRD remains low. The primary surgery should be vitrectomy combined with scleral buckling and silicone oil tamponade. Keywords: Stickler syndrome, retinopexy, Gulf States, Saudi Arabia, ocular genetics, arthro-ophthalmopathy, collagen disorder

Proliferative response of the murine esophageal epithelium to radiation: Modification by food consumption patterns

International Nuclear Information System (INIS)

Burholt, D.R.

1985-01-01

The single layer of proliferative epithelial cells of the murine esophagus undergoes a sequence of damage and recovery following cytotoxic insult. The modification of both damage and proliferative recovery by the alteration of animal eating patterns was investigated following thoracic field irradiation through the determination of /sup 3/H-TdR incorporation into the esophagus along with selective counting of labeled nuclei and mitotic figures. Initial radiation-induced damage, as determined by /sup 3/H-TdR incorporation suppression and mitotic delay, is under normal conditions dependent on the time of day of treatment. This circadian sensitivity may be altered by changing the eating pattern of the animal. The proliferative recovery following single dose irradiation is also dependent on food consumption patterns: fasting immediately following treatment and then refeeding 2 days later results in a more rapid proliferative recovery than observed under control eating conditions, while reduced food consumption during the period of proliferative hyperplasia reduces the extent of recovery. During multifraction radiation schedules both the damage produced by a subsequent dose and recovery capacity are influenced by the food consumption pattern between fractions

The differential proliferative ability of satellite cells in Lantang and Landrace pigs.

Directory of Open Access Journals (Sweden)

Xiu-qi Wang

Full Text Available Here, for the first time, we evaluate the hypothesis that the proliferative abilities of satellite cells (SCs isolated from Lantang (indigenous Chinese pigs and Landrace pigs, which differ in muscle characteristics, are different. SCs were isolated from the longissimus dorsi muscle of neonatal Lantang and Landrace pigs. Proliferative ability was estimated by the count and proliferative activity of viable cells using a hemocytometer and MTT assay at different time points after seeding, respectively. Cell cycle information was detected by flow cytometry. Results showed that there was a greater (P<0.05 number of SCs in Lantang pigs compared with Landrace pigs after 72 h of culture. The percentage of cell population in S phase and G(2/M phases in Lantang pigs were higher (P<0.05, while in G(0/G(1 phase was lower (P<0.05 in comparison with the Landrace pigs. The mRNA abundances of MyoD, Myf5, myogenin and Pax7 in SCs from Lantang pigs were higher (P<0.05, while those of myostatin, Smad3 and genes in the mammalian target of rapamycin (mTOR pathway (with the exception of 4EBP1 were lower (P<0.05 than the Landrace pigs. Protein levels of MyoD, myogenin, myostatin, S6K, phosphorylated mTOR and phosphorylated eIF4E were consistent with the corresponding mRNA abundance. Collectively, these findings suggested that SCs in the two breeds present different proliferative abilities, and the proliferative potential of SCs in Lantang pigs is higher than in Landrace pigs.

The development of proliferative verrucous leukoplakia in oral lichen planus. A preliminary study

Science.gov (United States)

Llorente-Pendás, Santiago; González-Garcia, Manuel; García-Martín, José-Manuel

2016-01-01

Background Was to describe 14 cases of a proliferative verrucous leukoplakia as a clinical evolution of oral lichen planus. Material and Methods The clinical and histopathological characteristics of 14 cases of OLP that progress towards a plaque-like and verrucous form were indicated, with monitoring over a period of six to 24.3 years. Results The female/male ratio was 11/3, (78.6 and 21.4%). The mean age when the first biopsy was undertaken was 56.4 years old. None of the patients smoked during the study. As bilateral reticular was clinically diagnostic criterion, the second most frequent clinical form was the plaque form (n=10; 71.4%), followed by the atrophic (n=6; 42.8%), and erosive forms (n=4; 28.5%). Clinically it spread towards attached gingival mucosa and the hard palate. In the histopathologic study, there were a predominance of hyperkeratosis and verrucous epithelial hyperplasia. Three of the cases progressed to a squamous cell carcinoma, and one patient developed two verrucous carcinoma. Conclusions Further research is needed to demonstrate if proliferative multifocal oral lichen planus and proliferative multifocal oral leukoplakia are the same disorder but have different behaviour of malignancy for reasons of origin. Key words:Oral lichen planus, proliferative verrucous oral leukoplakia, malignant oral lichen planus, multifocal verrucous oral lichen planus, proliferative verrucous oral lichen planus. PMID:27031060

Atypical hyperplasia, proliferative fibrocystic change, and exogenous hormone use.

Science.gov (United States)

Zera, R T; Danielson, D; Van Camp, J M; Schmidt-Steinbrunn, B; Hong, J; McCoy, M; Anderson, W R; Linzie, B M; Rodriguez, J L

2001-10-01

The association between breast cancer development and exogenous hormone use (EHU) is suggested by indirect clinical evidence. We undertook this study to better define the relationship that EHU has with proliferative fibrocystic change (PFC) and atypical hyperplasia (AH). Women diagnosed with AH without associated carcinoma from January 1990 to December 1999 were compared with control subjects who underwent breast biopsy procedures during the same interval and who were diagnosed with either a proliferative fibrocystic change (PFC) or a nonproliferative fibrocystic change (NPFC). EHU was defined as the use of estrogen or progesterone taken together or separately within 3 months of biopsy. EHU was significantly higher in patients with AH compared with women with NPFC (P =.01). This observation was also significant if all proliferative change (both AH and PFC) was compared with NPFC (P =.03); it was not significant when PFC alone was compared with NPFC. No significant difference in EHU was demonstrated between women with AH and those with PFC. There is strong association between AH and EHU. These results support the theory that a continuum exists between hyperplasia and carcinoma and that EHU may influence the transition from one to the other in an undefined subset of women. We encourage our patients with AH to discontinue EHU.

Different proliferative capacity of lung fibroblasts obtained from control subjects and patients with emphysema

NARCIS (Netherlands)

Noordhoek, JA; Postma, DS; Chong, LL; Vos, JTWM; Kauffman, HF; Timens, W; van Straaten, JFM

2003-01-01

To characterize the possible role of a dysregulated proliferative capacity of pulmonary fibroblasts in insufficient tissue repair in lungs from patients with pulmonary emphysema, the authors undertook in vitro proliferative studies with pulmonary fibroblasts obtained from lung tissue of patients

Genetic heterogeneity in familial exudative vitreoretinopathy; exclusion of the EVR1 locus on chromosome 11q in a large autosomal dominant pedigree.

Science.gov (United States)

Bamashmus, M A; Downey, L M; Inglehearn, C F; Gupta, S R; Mansfield, D C

2000-04-01

Familial exudative vitreoretinopathy (FEVR) is associated with mutations in the Norrie disease gene in X linked pedigrees and with linkage to the EVR1 locus at 11q13 in autosomal dominant cases. A large autosomal dominant FEVR family was studied, both clinically and by linkage analysis, to determine whether it differed from the known forms of FEVR. Affected members and obligate gene carriers from this family were examined by slit lamp biomicroscopy, indirect ophthalmoscopy, and in some cases fluorescein angiography. Patient DNAs were genotyped for markers at the EVR1 locus on chromosome 11q13. The clinical evaluation in this family is consistent with previous descriptions of FEVR pedigrees, but linkage analysis proves that it has a form of FEVR genetically distinct from the EVR1 locus on 11q. This proves that there are at least three different loci associated with comparable FEVR phenotypes, a situation similar to that existing for many forms of retinal degeneration.

Proliferative Activity and Neuroprotective Effect of Ligustrazene ...

African Journals Online (AJOL)

Proliferative Activity and Neuroprotective Effect of. Ligustrazene Derivative by Irritation of Vascular. Endothelial Growth Factor Expression in Middle Cerebral. Artery Occlusion Rats. Zhang Huazheng1, Wang Penglong2, Ren Liwei1, Wang Xiaobo2, Li Guoliang2,. Wang Mina1, Chu Fuhao2, Gong Yan2, Xu Bing2, Bi Siling1, ...

[A correlation between diffusion kurtosis imaging and the proliferative activity of brain glioma].

Science.gov (United States)

Tonoyan, A S; Pronin, I N; Pitshelauri, D I; Shishkina, L V; Fadeeva, L M; Pogosbekyan, E L; Zakharova, N E; Shults, E I; Khachanova, N V; Kornienko, V N; Potapov, A A

2015-01-01

The aim of the study was to assess the capabilities of diffusion kurtosis imaging (DKI) in diagnosis of the glioma proliferative activity and to evaluate a relationship between the glioma proliferative activity index and diffusion parameters of the contralateral normal appearing white matter (CNAWM). The study included 47 patients with newly diagnosed brain gliomas (23 low grade, 13 grade III, and 11 grade IV gliomas). We determined a relationship between absolute and normalized parameters of the diffusion tensor (mean (MD), axial (AD), and radial (RD) diffusivities; fractional (FA) and relative (RA) anisotropies) and diffusion kurtosis (mean (MK), axial (AK), and radial (RK) kurtosis; kurtosis anisotropy (KA)) and the proliferative activity index in the most malignant glioma parts (pAK, and RK) and anisotropy (KA, FA, RA) values increased, and diffusivity (MD, AD, RD) values decreased as the glioma proliferative activity index increased. A strong correlation between the proliferative activity index and absolute RK (r=0,71; p=0.000001) and normalized values of MK (r=0.8; p=0.000001), AK (r=0.71; p=0.000001), RK (r=0.81; p=0.000001), and RD (r=-0.71; p=0.000001) was found. A weak, but statistically significant correlation between the glioma proliferative activity index and diffusion values RK (r=-0.36; p=0.014), KA (r=-0.39; p=0.007), RD (r=0.35; p=0.017), FA (r=-0.42; p=0.003), and RA (r=-0.41; p=0.004) of CNAWM was found. DKI has good capabilities to detect immunohistochemical changes in gliomas. DKI demonstrated a high sensitivity in detection of microstructural changes in the contralateral normal appearing white matter in patients with brain gliomas.

Prevalence and 25 year incidence of proliferative retinopathy among Danish type 1 diabetic patients

DEFF Research Database (Denmark)

Grauslund, J; Green, A; Sjølie, A K

2009-01-01

AIMS/HYPOTHESIS: This study aimed to evaluate the prevalence of retinopathy in long-surviving type 1 diabetic patients. It also investigated the 25 year incidence of proliferative retinopathy and associated risk factors in a Danish population-based cohort. METHODS: A population-based cohort of 727...... type 1 diabetic patients from Fyn County, Denmark, was identified in 1973. In 1981-1982, baseline retinopathy was graded and other risk factors were assessed in 573 patients. Twenty-five years later, 308 patients were still alive. Of these, 201 (65.3%) were re-examined at follow-up in 2007......-2008. RESULTS: The median age and duration of diabetes at follow-up were 58.8 and 43 years, respectively. At follow-up, the prevalence of diabetic retinopathy was 97.0%. Non-proliferative retinopathy was found in 45.8%, and 51.2% had proliferative retinopathy. The 25 year incidence of proliferative retinopathy...

Comments on 'Standard effective doses for proliferative tumours'

International Nuclear Information System (INIS)

Dasu, Iuliana Livia; Dasu, Alexandru; Denekamp, Juliana; Fowler, Jack F.

2000-01-01

We should like to make some comments on the paper published by Jones et al (1999). The paper presents some interesting and useful contributions on the theoretical evaluation of different fractionated schedules used now. The use of the linear quadratic equation has been very useful in focusing attention on the differences in fractionation responses of fast and slow proliferating normal tissues and tumours. Unfortunately the BED 10 or BED 3 units for (α/β ratios of 10 Gy and 3 Gy respectively) do not directly relate to anything used in routine clinical practice. The purpose of the paper by Jones et al (1999) is to covert any new schedule into the equivalent total dose as if it was given in the same size fractions as are in common use in that department. They illustrate that, if proliferation is taken into account for the altered schedule, it can be compared in two ways with the standard conventional schedule: (a) the proliferative standard effective dose one (PSED 1 ) in which the proliferation correction is applied in the altered schedule, but not in the standard schedule; (b) the proliferative standard effective dose two (PSED 2 ) in which the proliferation correction is applied to both schedules using the same proliferation parameters. This is expected to provide a better evaluation of the response of a 'real' tumour (i.e. a tumour that also proliferates during the standard treatment). However, there seem to be two errors in the paper. First, the authors quoted a wrong equation for calculating the proliferative standard effective dose two (PSED 2 ) (equations (2) and (A6) in their paper). There are also some special cases with respect to the time available for proliferation and the duration of the treatment that have been neglected in their paper and which require further specification. Therefore, we should like to give the full mathematical derivation of the correct equations for calculating the proliferative standard effective doses. We would also like to make

Proliferation Index and Karyometric Features of Pancreatic Intraductal Proliferative Lesions

Directory of Open Access Journals (Sweden)

Romana Tomaszewska

1999-01-01

Full Text Available The increasing frequency and poor prognosis in pancreatic cancer prompt us to search for morphological lesions being a substrate for its development. Studies of autopsy and surgically resected material as well as recent molecular studies have proved that one of the possible pathways of pancreatic neoplasia is the intraepithelial proliferation – dysplasia – cancer sequence. In the present paper we studied the proliferative activity (Ki‐67 index in pancreatic intraepithelial proliferative lesions and its correlation with geometric features of cell nuclei as signs of increasing dysplasia. The studies were carried out in a group of 35 patients operated on for pancreatic cancer, chronic pancreatitis and other conditions not associated with the pancreas. We used immunohistochemical methods and basic morphometric parameters. The results of our studies indicate that the cell proliferative activity depends both on the type of epithelial proliferation and underlying pancreatic disease. The values of Ki‐67 index are significantly different in low‐grade proliferation (flat and papillary hyperplasia and high‐grade proliferation (atypical papillary hyperplasia and carcinoma in situ. A set of karyometric features correlates with Ki‐67 index but there is no single feature which would have a diagnostic value.

Rhegmatogenous retinal detachment and conventional surgical treatment.

Science.gov (United States)

Golubovic, M

2013-01-01

The aim of the paper was to present the efficacy and indications for application of conventional surgical treatment of retinal detachment by using external implants, that is,application of encircling band and buckle. This study comprised patients from the University Eye Clinic in Skopje. A total of 33 patients were diagnosed and surgically treated in the period between May 2010 and August 2011. Conventional surgery was applied in smaller number of patients whose changes of the vitreous body were manifested by detachment of posterior hyaloid membrane, syneresis, with appearance of a small number of pigment cells in the vitreous body and synchysis, and the very retina was with fresh detachment without folds or epiretinal changes (that is, PVR A grade). There were a larger number of patients with more distinct proliferative changes of the vitreous body and of the retina, grades PVR B to C1-C2, and who also underwent the same surgical approach. Routine ophthalmologic examinations were performed, including: determination of visual acuity by Snellen's optotypes, determination of eye pressure with Schiotz's tonometer, examination of anterior segment on biomicroscopy, indirect biomicroscopy of posterior eye segment (vitreous body and retina) and examination on biomicroscopy with Goldmann prism, B scan echography of the eyes before and after surgical treatment. Conventional treatment was used by external application of buckle or application of buckle and encircling band. In case of one break, radial buckle was applied and in case of multiple breaks in one quadrant limbus parallel buckle was applied. Besides buckle, encircling band was applied in patients with total or subtotal retinal detachment with already present distinct changes in the vitreous body (PVR B or C1-C2) and degenerative changes in the vitreous body. Breaks were closed with cryopexy. The results obtained have shown that male gender was predominant and that the disease was manifested in younger male adults

Differential expression of follistatin and FLRG in human breast proliferative disorders

Directory of Open Access Journals (Sweden)

Amaral Vania F

2009-09-01

Full Text Available Abstract Background Activins are growth factors acting on cell growth and differentiation. Activins are expressed in high grade breast tumors and they display an antiproliferative effect inducing G0/G1 cell cycle arrest in breast cancer cell lines. Follistatin and follistatin- related gene (FLRG bind and neutralize activins. In order to establish if these activin binding proteins are involved in breast tumor progression, the present study evaluated follistatin and FLRG pattern of mRNA and protein expression in normal human breast tissue and in different breast proliferative diseases. Methods Paraffin embedded specimens of normal breast (NB - n = 8; florid hyperplasia without atypia (FH - n = 17; fibroadenoma (FIB - n = 17; ductal carcinoma in situ (DCIS - n = 10 and infiltrating ductal carcinoma (IDC - n = 15 were processed for follistatin and FLRG immunohistochemistry and in situ hybridization. The area and intensity of chromogen epithelial and stromal staining were analyzed semi-quantitatively. Results Follistatin and FLRG were expressed both in normal tissue and in all the breast diseases investigated. Follistatin staining was detected in the epithelial cytoplasm and nucleus in normal, benign and malignant breast tissue, with a stronger staining intensity in the peri-alveolar stromal cells of FIB at both mRNA and protein levels. Conversely, FLRG area and intensity of mRNA and protein staining were higher both in the cytoplasm and in the nucleus of IDC epithelial cells when compared to NB, while no significant changes in the stromal intensity were observed in all the proliferative diseases analyzed. Conclusion The present findings suggest a role for follistatin in breast benign disease, particularly in FIB, where its expression was increased in stromal cells. The up regulation of FLRG in IDC suggests a role for this protein in the progression of breast malignancy. As activin displays an anti-proliferative effect in human mammary cells, the

In vitro anti-proliferative effect of interferon alpha in solid tumors: A potential predicative test

International Nuclear Information System (INIS)

Fuchsberger, N.; Kubes, M.; Kontsek, P.; Borecky, L.; Hornak, M.; Silvanova; Godal, A.; Svec, J.

1993-01-01

An in vitro test for the anti-proliferative effect of human leukocyte interferon (IFN-alpha) was performed in primary cultures of tumor cells obtained from 32 patients with either malignant melanoma (13), renal carcinoma (4) or bladder carcinoma (15). Our results demonstrated activity of IFN in all three groups of solid tumors. However, appreciable differences in sensitivity to anti-proliferative effect of IFN between individual tumors of the same type were found. The potential of this anti-proliferative test for prediction of treatment response in IFN-therapy is discussed. (author)

Identification of a fourth locus (EVR4) for familial exudative vitreoretinopathy (FEVR).

Science.gov (United States)

Toomes, Carmel; Downey, Louise M; Bottomley, Helen M; Scott, Sheila; Woodruff, Geoffrey; Trembath, Richard C; Inglehearn, Chris F

2004-01-15

Familial exudative vitreoretinopathy (FEVR) is a genetically heterogeneous inherited blinding disorder of the retinal vascular system. To date three loci have been mapped: EVR1 on chromosome 11q, EVR2 on chromosome Xp, and EVR3 on chromosome 11p. The gene underlying EVR3 remains unidentified whilst the EVR2 gene, which encodes the Norrie disease protein (NDP), was identified over a decade ago. More recently, FZD4, the gene that encodes the Wnt receptor Frizzled-4, was identified as the mutated gene at the EVR1 locus. The purpose of this study was to screen FZD4 in a large family previously proven to be linked to the EVR1 locus. PCR products were generated using genomic DNA from affected family members with primers designed to amplify the coding sequence of FZD4. The PCR products were screened for mutations by direct sequencing. Genotyping was performed in all available family members using fluorescently labeled microsatellite markers from chromosome 11q. Sequencing of the EVR1 gene, FZD4, in this family identified no mutation. To investigate this family further we performed high-resolution genotyping with markers spanning chromosome 11q. Haplotype analysis excluded FZD4 as the mutated gene in this family and identified a candidate region approximately 10 cM centromeric to EVR1. This new FEVR locus is flanked by markers D11S1368 (centromeric) and D11S937 (telomeric) and spans approximately 15 cM. High-resolution genotyping and haplotype analysis excluded FZD4 as the defective gene in a family previously linked to the EVR1 locus. The results indicate that the gene mutated in this family lies centromeric to the EVR1 gene, FZD4, and is also genetically distinct from the EVR3 locus. This new locus has been designated EVR4 and is the fourth FEVR locus to be described.

Automatic non-proliferative diabetic retinopathy screening system based on color fundus image.

Science.gov (United States)

Xiao, Zhitao; Zhang, Xinpeng; Geng, Lei; Zhang, Fang; Wu, Jun; Tong, Jun; Ogunbona, Philip O; Shan, Chunyan

2017-10-26

Non-proliferative diabetic retinopathy is the early stage of diabetic retinopathy. Automatic detection of non-proliferative diabetic retinopathy is significant for clinical diagnosis, early screening and course progression of patients. This paper introduces the design and implementation of an automatic system for screening non-proliferative diabetic retinopathy based on color fundus images. Firstly, the fundus structures, including blood vessels, optic disc and macula, are extracted and located, respectively. In particular, a new optic disc localization method using parabolic fitting is proposed based on the physiological structure characteristics of optic disc and blood vessels. Then, early lesions, such as microaneurysms, hemorrhages and hard exudates, are detected based on their respective characteristics. An equivalent optical model simulating human eyes is designed based on the anatomical structure of retina. Main structures and early lesions are reconstructed in the 3D space for better visualization. Finally, the severity of each image is evaluated based on the international criteria of diabetic retinopathy. The system has been tested on public databases and images from hospitals. Experimental results demonstrate that the proposed system achieves high accuracy for main structures and early lesions detection. The results of severity classification for non-proliferative diabetic retinopathy are also accurate and suitable. Our system can assist ophthalmologists for clinical diagnosis, automatic screening and course progression of patients.

Analysis of in situ proliferative activity in oral gingival epithelium in patients with xerostomia.

Science.gov (United States)

Celenligil-Nazliel, Haviye; Palali, Ali; Ayhan, Ayşe; Ruacan, Sevket

2003-02-01

Sjögren's syndrome is an autoimmune disease characterized by xerostomia and keratoconjunctivitis sicca. The relationship between xero-stomia and proliferative activity in human gingival epithelium is not known. Proliferating cell nuclear antigen (PCNA) is a nuclear protein associated with the cell cycle. Nuclear PCNA immunoreactivity is found in the proliferative compartment of normal tissues. The aims of this study were to evaluate PCNA expression in oral gingival epithelium of healthy and inflamed gingiva obtained from patients with Sjögren's syndrome, and to compare the results to age- and gender-matched subjects with normal salivary function. Eighteen Sjögren's syndrome patients and 28 controls (14 with chronic periodontitis and 14 with no clinical evidence of periodontal disease) were included in the study. Biopsies were obtained from both inflamed and healthy gingiva. The expression of PCNA was evaluated in formalin-fixed, paraffin-embedded gingival samples using an immunoperoxidase technique and PC10 monoclonal antibody to PCNA. PCNA expression was observed both in the basal and suprabasal layers, and was found to be more prominent in the suprabasal layers. Proliferative index (PI) in inflamed gingiva was significantly lower in the Sjögren's syndrome group. However, no significant difference was observed between the study and control groups with respect to PI in healthy gingiva. In both groups, PI was found to be increased due to inflammation. Our data indicate that proliferative activity is observed in the suprabasal layers and, less frequently, in the basal layer. Inflammation caused increased proliferative activity. However, this positive effect of inflammation on epithelial cell proliferation decreased significantly with a lack of saliva. Therefore, it appears that saliva-derived biological mediators may also contribute to increased proliferative activity observed during inflammation.

A Predictive Model for Estimation Risk of Proliferative Lupus Nephritis

Directory of Open Access Journals (Sweden)

Dong-Ni Chen

2018-01-01

Conclusion: This study developed and validated a model including demographic and clinical indices to evaluate the probability of presenting proliferative LN to guide therapeutic decisions and outcomes.

Cetuximab-Associated Crescentic Diffuse Proliferative Glomerulonephritis

Directory of Open Access Journals (Sweden)

Sukesh Manthri

2017-01-01

Full Text Available Cetuximab-induced nephrotoxicity is very rare, occurring in less than 1% of colorectal cancer patients and not defined in other populations. We report a rare case of crescentic diffuse proliferative glomerulonephritis (GN that developed in close temporal association with cetuximab treatment. A 65-year-old female recently completed chemotherapy with cetuximab treatment for moderately differentiated oral squamous cell carcinoma. She was admitted with acute renal failure and nephrotic-range proteinuria. Laboratory data showed serum creatinine of 6.6 mg/dl and urinalysis showed proteinuria, moderate hemoglobinuria, hyaline casts (41/LPF, WBC (28/HPF, and RBC (81/HPF. Serologic studies were negative for ANA, anti-GBM, ANCA, hepatitis B, and hepatitis C. Serum C3 and C4 level were normal. Renal biopsy showed crescentic diffuse proliferative GN with focal features of thrombotic microangiopathy. Patient was started on cyclophosphamide and steroids. Her renal function did not improve on day 8 and she was started on hemodialysis. Previous reports suggest that EGFR-targeting medications can possibly trigger or exacerbate an IgA-mediated glomerular process leading to renal failure. This case suggests that cetuximab therapy may have triggered or exacerbated a severe glomerular injury with an unfavorable outcome. Treating physicians should maintain a high degree of caution and monitor renal function in patients on EGFR inhibitors.

Anti-proliferative activity of recombinant melittin expressed in ...

African Journals Online (AJOL)

Recombinant melittin was then successfully expressed in Escherichia coli. The activity of affinity-purified recombinant melittin was determined in human leukemic U937 cells. Results show that the recombinant melittin had the same anti-proliferative activity in human leukemic U937 cells in vitro as natural one. This shows the ...

Antioxidant and Anti-proliferative Activities of Flavonoids from ...

African Journals Online (AJOL)

Purpose: To investigate the chemical composition of Bidens pilosa L. var. radiata. Sch Bip. (BP), as well as its antioxidant and anti-proliferative activities. Methods: The whole herb of BP was extracted with 95 % ethanol, which was then partitioned sequentially with petroleum ether, ethyl acetate and n-butyl alcohol to obtain ...

Proliferative, necrotizing and crescentic immune complex-mediated glomerulonephritis in a cat

Directory of Open Access Journals (Sweden)

Carolyn Gross

2015-09-01

Full Text Available Case Summary A 5-year-old cat was examined for vomiting and anorexia of 2 days’ duration. Azotemia, hyperphosphatemia and hypoalbuminemia were the main biochemical findings. Serial analyses of the urine revealed isosthenuria, proteinuria and eventual glucosuria. Hyperechoic perirenal fat was detected surrounding the right kidney by ultrasonography. Histopathologic evaluation of ante-mortem ultrasound-guided needle biopsies of the right kidney was consistent with proliferative, necrotizing and crescentic glomerulonephritis with fibrin thrombi, proteinaceous and red blood cell casts, and moderate multifocal chronic-active interstitial nephritis. Owing to a lack of clinical improvement, the cat was eventually euthanized. Post-mortem renal biopsies were processed for light microscopy, transmission electron microscopy and immunofluorescence. This revealed severe focal proliferative and necrotizing glomerulonephritis with cellular crescent formation, podocyte injury and secondary segmental sclerosis. Ultrastructural analysis revealed scattered electron-dense deposits in the mesangium, and immunofluorescence demonstrated positive granular staining for λ light chains, consistent with immune complex-mediated glomerulonephritis. Severe diffuse acute tubular epithelial injury and numerous red blood cell casts were also seen. Relevance and novel information To our knowledge, this is the first report of naturally occurring proliferative, necrotizing and crescentic immune complex glomerulonephritis in a cat.

Retinal vessel caliber as a potential marker of treatment outcome in patients with proliferative diabetic retinopathy

DEFF Research Database (Denmark)

Vergmann, Anna Stage; Torp, Thomas Lee; Lundberg, Kristian

Title of abstract: Retinal vessel caliber as a potential marker of treatment outcome in patients with proliferative diabetic retinopathy Design of study: Three months prospective, interventional clinical study. Purpose: The retinal vascular tree can be measured non-invasively and summarized...... into the central retinal artery and vein equivalent (CRAE and CRVE). The purpose of this study was to evaluate retinal calibers as biomarkers for disease activity 3 months after panretinal photocoagulation (PRP) in patients with proliferative diabetic retinopathy (PDR). Methods: Fifty one eyes from 40 newly...... with proliferative diabetic retinopathy....

VISUAL OUTCOME FOLLOWING PANRETINAL PHOTOCOAGULATION IN PROLIFERATIVE DIABETIC RETINOPATHY

Directory of Open Access Journals (Sweden)

Nellaye Mani Sindhu

2018-01-01

Full Text Available BACKGROUND Diabetes mellitus can be called as a noninfectious pandemic and the incidence of diabetic retinopathy is also uncontrollable. This vision-threatening complication can be treated by early diagnosis and effective treatment like panretinal photocoagulation. The aim of the study is to evaluate the effect of panretinal photocoagulation on visual acuity, colour vision, contrast sensitivity and severity of visual field changes. MATERIALS AND METHODS Prospective study of visual outcome following panretinal photocoagulation in patients with proliferative diabetic retinopathy conducted in Retina Clinic, RIO, Trivandrum, during the time period one year from April 2008. Inclusion Criteria- Eyes with proliferative diabetic retinopathy, visual acuity better than or equal to 6/60, a follow up of at least 6 months after panretinal photocoagulation. Exclusion Criteria- Eyes with cataractous changes in the lens, eyes, which would be undergoing or have undergone focal photocoagulation eyes, which undergone barrage or sectoral retinal photocoagulation, patients with colour blindness, eyes with vitreous haemorrhage and macular preretinal haemorrhage, glaucomatous patients with peripheral field loss. RESULTS The mean age of the patients was 52 years. Male patients (30 outnumbered the female patients (23. Mean duration of diabetes was 14.42 years. Though, there is a statistically significant reduction in visual acuity in the first followup, which was improved and stabilised by 6 months. There is a statistically significant reduction in the contrast sensitivity, which was stabilised after 3 months. Only, 9.5% patients had peripheral constrictions of visual field and no significant change in the colour vision. CONCLUSION We recommend panretinal photocoagulation for all patients with proliferative diabetic retinopathy.

Targeted next-generation sequencing analysis identifies novel mutations in families with severe familial exudative vitreoretinopathy

Science.gov (United States)

Huang, Xiao-Yan; Zhuang, Hong; Wu, Ji-Hong; Li, Jian-Kang; Hu, Fang-Yuan; Zheng, Yu; Tellier, Laurent Christian Asker M.; Zhang, Sheng-Hai; Gao, Feng-Juan; Zhang, Jian-Guo

2017-01-01

Purpose Familial exudative vitreoretinopathy (FEVR) is a genetically and clinically heterogeneous disease, characterized by failure of vascular development of the peripheral retina. The symptoms of FEVR vary widely among patients in the same family, and even between the two eyes of a given patient. This study was designed to identify the genetic defect in a patient cohort of ten Chinese families with a definitive diagnosis of FEVR. Methods To identify the causative gene, next-generation sequencing (NGS)-based target capture sequencing was performed. Segregation analysis of the candidate variant was performed in additional family members by using Sanger sequencing and quantitative real-time PCR (QPCR). Results Of the cohort of ten FEVR families, six pathogenic variants were identified, including four novel and two known heterozygous mutations. Of the variants identified, four were missense variants, and two were novel heterozygous deletion mutations [LRP5, c.4053 DelC (p.Ile1351IlefsX88); TSPAN12, EX8Del]. The two novel heterozygous deletion mutations were not observed in the control subjects and could give rise to a relatively severe FEVR phenotype, which could be explained by the protein function prediction. Conclusions We identified two novel heterozygous deletion mutations [LRP5, c.4053 DelC (p.Ile1351IlefsX88); TSPAN12, EX8Del] using targeted NGS as a causative mutation for FEVR. These genetic deletion variations exhibit a severe form of FEVR, with tractional retinal detachments compared with other known point mutations. The data further enrich the mutation spectrum of FEVR and enhance our understanding of genotype–phenotype correlations to provide useful information for disease diagnosis, prognosis, and effective genetic counseling. PMID:28867931

Scoring radiologic characteristics to predict proliferative potential in meningiomas

International Nuclear Information System (INIS)

Hashiba, Tetsuo; Hashimoto, Naoya; Maruno, Motohiko; Izumoto, Shuichi; Suzuki, Tsuyoshi; Kagawa, Naoki; Yoshimine, Toshiki

2006-01-01

We investigated the feasibility of using radiologic characteristics to predict the proliferative potential in meningiomas. Our statistical analysis revealed that the presence of peritumoral edema, an ambiguous brain-tumor border, and irregular tumor shape were significantly correlated with a higher MIB-1 staining index (SI) value. We developed the following scoring system for specific features in each tumor: peritumoral edema (tumor with edema=1, tumor without edema=0); brain-tumor border (tumor with any ambiguous border=1, tumor circumscribed by a distinct rim=0); and tumor shape (tumor with irregular shape=1, tumor with smooth shape=0). Using Spearman's correlation coefficient analysis, we found a significant correlation (P<0.005) between total score calculated for each patient and SI value. Our findings suggest that the proliferative potential of meningiomas can be predicted using a less invasive preoperative examination focusing on the presence of peritumoral edema, ambiguous brain-tumor border, and irregular tumor shape. (author)

Identification of novel missense mutations in the Norrie disease gene associated with one X-linked and four sporadic cases of familial exudative vitreoretinopathy.

Science.gov (United States)

Shastry, B S; Hejtmancik, J F; Trese, M T

1997-01-01

X-linked Familial Exudative Vitreoretinopathy (XLFEVR) is a hereditary eye disorder that affects both the retina and the vitreous body. It is characterized by an abnormal vascularization of the peripheral retina. It has been previously shown by linkage and candidate gene analysis that XLFEVR and Norrie disease are allelic. In this report we describe four novel mutations (R41K, H42R, K58N, and Y120C) in the Norrie disease gene associated with one X-linked and four sporadic cases of FEVR. One mutation (H42R) was found to be segregating with the disease in three generations (X-linked family), and the others are sporadic. These sequence alterations changed the encoded amino acids in the Norrie disease protein and were not found in 17 unaffected family members or in 36 randomly selected normal individuals. This study provides additional evidence that mutations in the same gene can result in FEVR and Norrie disease. It also demonstrates that it may be beneficial for clinical diagnosis to screen for mutations in the Norrie disease gene in sporadic FEVR cases.

Anti-proliferative effect of Moringa oleifera Lam (Moringaceae) leaf ...

African Journals Online (AJOL)

Purpose: To investigate the in vitro anti-proliferative effect and mechanism of action of Moringa oleifera Lam. leaf extract on human colon carcinoma HCT116 cell line. Methods: M. oleifera leaves were extracted with methanol. It was fractionated by Sephadex LH-20 column chromatography. Several fractions were identified ...

Body linear traits for identifying prolific goats

Directory of Open Access Journals (Sweden)

Avijit Haldar

2014-12-01

Full Text Available Aim: The present study was conducted on prolific goat breed to identify body linear type traits that might be associated with prolificacy trait in goats. Materials and Methods: Two-stage stratified random sample survey based data were collected from 1427 non-pregnant goats with the history of single, twin and triplet litter sizes (LZ between January 2008 to February 2011 for 3 years in 68 villages located in East and North East India. Data on sixteen body linear traits were analyzed using logistic regression model to do the step-wise selection for identifying the body linear traits that could determine LZ. An average value for each identified body linear trait was determined for classifying the goats into three categories: Goats having the history of single LZ, goats having the history of twin LZ and goats having the history of triplet LZ. Results: The LZ proportions for single, twin and triplet, were 29.50, 59.14 and 11.36%, respectively, with the prolificacy rate of 181.85% in Indian Black Bengal goats. A total of eight body linear traits that could determine LZ in prolific goats were identified. Heart girth (HG measurement (>60.90 cm, paunch girth (PG (>70.22 cm, wither height (WH (>49.75 cm, neck length (>21.45 cm, ear length (>12.80 cm and distance between trochanter major (DTM bones (>12.28 cm, pelvic triangle area (PTA (>572.25 cm2 and clearance at udder (CU (>23.16 cm showed an increase likelihood of multiple LZ when compared to single LZ. Further, HG measurement (>62.29 cm, WH (>50.54 cm, PG (>71.85 cm and ear length (>13.00 cm, neck length (>22.01 cm, PTA (>589.64 cm2, CU (>23.20 cm and DTM bones (>12.47 cm were associated with increased likelihood of triplet LZ, when compared with that of twin LZ. Conclusion: HG measurement was the best discriminating factor, while PG, neck length, DTM bones, CU, PTA, WH and ear length measurements were other important factors that could be used for identifying prolific goats to achieve economic

Proliferative Retinopathy in Type 1 Diabetes Is Associated With Cerebral Microbleeds, Which Is Part of Generalized Microangiopathy

NARCIS (Netherlands)

Woerdeman, J.P.; van Duinkerken, E.; Wattjes, M.P.; Barkhof, F.; Snoek, F.J.; Moll, A.C.; Klein, M.; de Boer, M.P.; IJzerman, R.G.; Serne, E.H.; Diamant, M.

2014-01-01

OBJECTIVE: We investigated whether proliferative diabetic retinopathy in type 1 diabetic patients can be generalized to cerebral small vessel disease and whether it is associated with impaired peripheral microvascular function. RESEARCH DESIGN AND METHODS: Thirty-three patients with proliferative

Proliferative and morphologic changes in rat colon following bypass surgery.

Science.gov (United States)

Barkla, D H; Tutton, P J

1985-06-01

In this study the proliferative and morphologic changes that occur in the colon of normal and dimethylhydrazine-treated rats following surgical bypass of the middle third of the colon are reported. Proliferative changes were measured by estimating accumulated mitotic indexes following vinblastine treatment and morphologic changes were observed with the use of light microscopy and scanning electron microscopy. Data were collected on Days 0, 7, 14, 30, and 72 after surgery. The results show that surgical bypass produces contrasting effects in the segments proximal to and distal to the suture line. In the proximal segment there was morphologic evidence of hyperplasia, although proliferative activity was unchanged except for an increase at 7 days in normal rats. In the distal segment there was a long-lived increase in the mitotic index, although morphologic changes were not seen. The results for DMH-treated rats were similar to those in normal rats. Groups of isolated dysplastic epithelial cells were often seen in the submucosa adjacent to sutures up to 72 days after surgery. Increased lymphoid infiltration was seen in segments proximal to but not distal to the suture line. It is hypothesized that the different responses of the proximal and distal segments may be related to the different embryologic origins of those segments. It is also hypothesized that the seeding of the submucosa with epithelial cells during suturing may be a factor in tumor recurrence.

Too much of a good thing? An observational study of prolific authors.

Science.gov (United States)

Wager, Elizabeth; Singhvi, Sanjay; Kleinert, Sabine

2015-01-01

Introduction. Researchers' productivity is usually measured in terms of their publication output. A minimum number of publications is required for some medical qualifications and professional appointments. However, authoring an unfeasibly large number of publications might indicate disregard of authorship criteria or even fraud. We therefore examined publication patterns of highly prolific authors in 4 medical specialties. Methods. We analysed Medline publications from 2008-12 using bespoke software to disambiguate individual authors focusing on 4 discrete topics (to further reduce the risk of combining publications from authors with the same name and affiliation). This enabled us to assess the number and type of publications per author per year. Results. While 99% of authors were listed on fewer than 20 publications in the 5-year period, 24 authors in the chosen areas were listed on at least 25 publications in a single year (i.e., >1 publication per 10 working days). Types of publication by the prolific authors varied but included substantial numbers of original research papers (not simply editorials or letters). Conclusions. Institutions and funders should be alert to unfeasibly prolific authors when measuring and creating incentives for researcher productivity.

Too much of a good thing? An observational study of prolific authors

Directory of Open Access Journals (Sweden)

Elizabeth Wager

2015-08-01

Full Text Available Introduction. Researchers’ productivity is usually measured in terms of their publication output. A minimum number of publications is required for some medical qualifications and professional appointments. However, authoring an unfeasibly large number of publications might indicate disregard of authorship criteria or even fraud. We therefore examined publication patterns of highly prolific authors in 4 medical specialties.Methods. We analysed Medline publications from 2008–12 using bespoke software to disambiguate individual authors focusing on 4 discrete topics (to further reduce the risk of combining publications from authors with the same name and affiliation. This enabled us to assess the number and type of publications per author per year.Results. While 99% of authors were listed on fewer than 20 publications in the 5-year period, 24 authors in the chosen areas were listed on at least 25 publications in a single year (i.e., >1 publication per 10 working days. Types of publication by the prolific authors varied but included substantial numbers of original research papers (not simply editorials or letters.Conclusions. Institutions and funders should be alert to unfeasibly prolific authors when measuring and creating incentives for researcher productivity.

Disease: H01798 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available H01798 Autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV) Autos...omal dominant neovascular inflammatory vitreoretinopathy (ADNIV) is an inherited autoimmune uveitis and vitr... ... Secondary glaucoma in CAPN5-associated neovascular inflammatory vitreoretinopathy. ... JOURNAL ... Clin Ophtha

Prolific plant regeneration through organogenesis from scalps of ...

African Journals Online (AJOL)

Four types of potting media comprising of sand, peat, sand + top soil + goat dung (3:2:1 v/v) and top soil + sand (1:1 v/v) were evaluated during acclimatization of the plantlets. Prolific shoot regeneration from scalps was obtained on MS medium containing 2.5 mM BAP, at 9.61 and 40.6 shoots per explant after 4 and 8 weeks ...

Effect of С(60 fullerene on metabolic and proliferative activity of PKE cell line

Directory of Open Access Journals (Sweden)

I. V. Belochkina

2014-04-01

Full Text Available The effect of С60 fullerene aqueous colloid solution (C60FAS on activity of redox and proliferative processes in PKE (transplantable cell line of pig kidney embryo cells has been studied. In particular, it was established that the presence of С60 fullerene (127 μМ in culturing medium of PKE cells during 48 h did not change their ability to reduce non-toxic АlamarBlue redox indicator and proliferative acti­vity.

Proliferative myositis in a patient with AIDS

International Nuclear Information System (INIS)

Wlachovska, B.; Deux, J.F.; Marsault, C.; Le Breton, C.; Abraham, B.; Sibony, M.

2004-01-01

We report a case of proliferative myositis in the right biceps of a 56-year-old man with acquired immune deficiency syndrome (AIDS). Imaging methods included sonography, computed tomography and magnetic resonance imaging. The diagnosis was made by a core-cut biopsy and fine needle aspiration biopsy with immunohistochemical analysis. The lesion disappeared after 2 months without treatment. It is particularly important to determine whether intramuscular masses arising in patients with AIDS are due to an infectious or malignant process. (orig.)

Proliferative myositis in a patient with AIDS

Energy Technology Data Exchange (ETDEWEB)

Wlachovska, B.; Deux, J.F.; Marsault, C.; Le Breton, C. [Department of Radiology, Hopital Tenon, 4 rue de la Chine, 75020, Paris (France); Abraham, B. [Department of Tropical and Infectious Diseases, Hopital Tenon, Paris (France); Sibony, M. [Department of Anatomy, Hopital Tenon, Paris (France)

2004-04-01

We report a case of proliferative myositis in the right biceps of a 56-year-old man with acquired immune deficiency syndrome (AIDS). Imaging methods included sonography, computed tomography and magnetic resonance imaging. The diagnosis was made by a core-cut biopsy and fine needle aspiration biopsy with immunohistochemical analysis. The lesion disappeared after 2 months without treatment. It is particularly important to determine whether intramuscular masses arising in patients with AIDS are due to an infectious or malignant process. (orig.)

Dutch guidelines for diagnosis and therapy of proliferative lupus nephritis

NARCIS (Netherlands)

van Tellingen, A.; Voskuyl, A. E.; Vervloet, M. G.; Bijl, M.; de Sevaux, R. G. L.; Berger, S. P.; Derksen, R. H. W. M.; Berden, J. H. M.

Proliferative lupus nephritis is a strong predictor of morbidity and mortality in patients with systemic lupus erythematosus. Despite improvements in the management of lupus nephritis, a significant number of the patients do not respond to immunosuppressive therapy and progress to end-stage renal

uPAR EXPRESSION IN CANINE NORMAL PROSTATE AND WITH PROLIFERATIVE DISORDERS

Directory of Open Access Journals (Sweden)

Mariana Rodrigues Faleiro

2013-06-01

Full Text Available Prostatic lesions such as prostatic intraepithelial neoplasia (PIN and proliferative inflammatory atrophy (PIA are studied in human and canine species due to their malignance potential. The plasminogen activator (PA system has been suggested to play a central role in cell adhesion, angiogenesis, inflammation, and tumor invasion. The urokinase-type plasminogen activator receptor (uPAR is a component of the PA, with a range of expression in tumor and stromal cells. In this study, uPAR expression in both canine normal prostates and with proliferative disorders (benign prostatic hyperplasia-BPH, proliferative inflammatory atrophy-PIA, prostatic intraepithelial neoplasia-PIN, and carcinoma-PC was evaluated by immunohistochemistry in a tissue microarray (TMA slide to establish the role of this enzyme in extracellular matrix (ECM remodeling and in the processes of tissue invasion. A total of 298 cores and 355 diagnoses were obtained, with 36 (10.1% normal prostates, 46 (13.0% with BPH, 128 (36.1% with PIA, 74 (20.8% with PIN and 71 (20.0% with PC. There is variation in the expression of uPAR in canine prostate according to the lesion, with lower expression in normal tissue and with BPH, and higher expression in tissue with PIA, PIN and PC. The high expression of uPAR in inflammatory and neoplastic microenvironment indicates increased proteolytic activity in canine prostates with PIA, PIN, and PC.

Pharmacologic Activation of Wnt Signaling by Lithium Normalizes Retinal Vasculature in a Murine Model of Familial Exudative Vitreoretinopathy.

Science.gov (United States)

Wang, Zhongxiao; Liu, Chi-Hsiu; Sun, Ye; Gong, Yan; Favazza, Tara L; Morss, Peyton C; Saba, Nicholas J; Fredrick, Thomas W; He, Xi; Akula, James D; Chen, Jing

2016-10-01

Familial exudative vitreoretinopathy (FEVR) is characterized by delayed retinal vascular development, which promotes hypoxia-induced pathologic vessels. In severe cases FEVR may lead to retinal detachment and visual impairment. Genetic studies linked FEVR with mutations in Wnt signaling ligand or receptors, including low-density lipoprotein receptor-related protein 5 (LRP5) gene. Here, we investigated ocular pathologies in a Lrp5 knockout (Lrp5(-/-)) mouse model of FEVR and explored whether treatment with a pharmacologic Wnt activator lithium could bypass the genetic defects, thereby protecting against eye pathologies. Lrp5(-/-) mice displayed significantly delayed retinal vascular development, absence of deep layer retinal vessels, leading to increased levels of vascular endothelial growth factor and subsequent pathologic glomeruloid vessels, as well as decreased inner retinal visual function. Lithium treatment in Lrp5(-/-) mice significantly restored the delayed development of retinal vasculature and the intralaminar capillary networks, suppressed formation of pathologic glomeruloid structures, and promoted hyaloid vessel regression. Moreover, lithium treatment partially rescued inner-retinal visual function and increased retinal thickness. These protective effects of lithium were largely mediated through restoration of canonical Wnt signaling in Lrp5(-/-) retina. Lithium treatment also substantially increased vascular tubular formation in LRP5-deficient endothelial cells. These findings suggest that pharmacologic activation of Wnt signaling may help treat ocular pathologies in FEVR and potentially other defective Wnt signaling-related diseases. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Evaluation of the anti-proliferative and cytotoxic potentials of ...

African Journals Online (AJOL)

The partitioned aqueous and chloroform fractions obtained from the methanol extract of the leaf of Cnidoscolus aconitifolius were examined for anti-proliferative (1-30 mg/mL) and cytotoxic activities (20-400 μg/mL) using the seed radicle inhibition and tadpole mortality assays over a period of 24 and 96 h respectively.

Novel and recurrent NDP gene mutations in familial cases of Norrie disease and X-linked exudative vitreoretinopathy.

Science.gov (United States)

Pelcastre, Erika L; Villanueva-Mendoza, Cristina; Zenteno, Juan C

2010-05-01

To present the results of molecular analysis of the NDP gene in Mexican families with Norrie disease (ND) and X-linked familial exudative vitreoretinopathy (XL-FEVR). Two unrelated families with ND and two with XL-FEVR were studied. Clinical diagnosis was suspected on the basis of a complete ophthalmologic examination. Molecular methods included DNA isolation from peripheral blood leucocytes, polymerase chain reaction amplification and direct nucleotide sequencing analysis of the complete coding region and exon-intron junctions of NDP. Haplotype analysis using NDP-linked microsatellites markers was performed in both ND families. A novel Norrin missense mutation, p.Arg41Thr, was identified in two apparently unrelated families with ND. Haplotype analysis demonstrated that affected males in these two families shared the same ND-linked haplotype, suggesting a common origin for this novel mutation. The previously reported p.Arg121Trp and p.Arg121Gln Norrin mutations were identified in the two families with XL-FEVR. Our results expand the mutational spectrum in ND. This is the first report of ND resulting from mutation at arginine position 41 of Norrin. Interestingly, mutations at the same residue but resulting in a different missense change were previously described in subjects with XL-FEVR (p.Arg41Lys) or persistent fetal vasculature syndrome (p.Arg41Ser), indicating that the novel p.Arg41Thr change causes a more severe retinal phenotype. Preliminary data suggest a founder effect for the ND p.Arg41Thr mutation in these two Mexican families.

Antibacterial, antioxidant and cell proliferative properties of Coccinia grandis fruits

Directory of Open Access Journals (Sweden)

Prashant Sakharkar

2017-06-01

Full Text Available Objective: Little knowledge is available on the antimicrobial and antioxidant properties of Coccina grandis fruits and no study has reported on its cell proliferative property. The aim of this study was to examine the antimicrobial, antioxidant and cell proliferative property of fruits of C. grandis. Material and Methods: Fruits of C. grandis were extracted using water; ethanol and acetone by cold and hot Soxhlet extraction. The antibacterial activities of the extracts were tested against Staphylococcus aureus, Enterococcus faecalis, Escherichia coli and Pseudomonas aeruginosa using the modified Kirby-Bauer diffusion method and compared against erythromycin. The antioxidant property was determined using Cayman's antioxidant assay; whereas cell proliferation/cytotoxic properties were evaluated using the Cell Titer 96 Aqueous One Solution Cell MTS assay with MDA-MB 321 breast cancer cells. Data were analyzed for correlation and differences using unpaired student's t-test and one-way ANOVA. A p value of Results: Both cold and hot ethanol and acetone extracts of C. grandis fruits showed some degree of bacterial growth inhibition. Acetone extracts exhibited higher antibacterial activity. Both ethanol extracts showed antioxidant property when compared with standard Trolox. In contrary to cytotoxicity, all four extracts showed cell proliferation compared to controls at different concentrations. However, acetone extracts exhibited greater cell proliferation compared to ethanol extracts and cold extracts performed better than the hot extracts. Conclusion: C. grandis fruits exhibited some degree of antimicrobial, antioxidant and cell proliferative properties. Further investigation is warranted to isolate, confirm and characterize phytochemicals that are responsible for the medicinal properties observed.

Proliferative and nonproliferative breast disease in atomic-bomb survivors

International Nuclear Information System (INIS)

Tokunaga, Masayoshi; Land, C.E.; Aoki, Yoichiro; Yamamoto, Tsutomu; Asano, Masahide; Sato, Eiichi; Tokuoka, Shoji; Sakamoto, Goi; Page, D.L.

1993-10-01

The risk of female breast cancer in association with radiation exposure is well established, on the basis of follow-up studies of the atomic-bomb survivors and other exposed populations. This association is especially strong for women exposed before age 20 yr and appears to be much weaker among women exposed after age 40 yr. In this study, breast-tissue autopsy samples from high-dose and low-dose individuals in the Radiation Effects Research Foundation Life Span Study sample were examined in detail to determine whether nonproliferative or proliferative breast lesions are associated with radiation exposure. The results suggest that proliferative disease in general and atypical hyperplasia in particular are associated with radiation exposure and that the risk is strongest for subjects who were ages 40-49 yr at the time of the bombings. It is hypothesized that this finding may be related to the age dependence of radiation-induced breast cancer, in the sense that potential cancers reflecting early-stage changes induced at these ages by radiation exposure may receive too little hormonal promotion to progress to frank cancers. (author)

Chemical Constituents from Cimicifuga dahurica and Their Anti-Proliferative Effects on MCF-7 Breast Cancer Cells.

Science.gov (United States)

Huyen, Chu Thi Thanh; Luyen, Bui Thi Thuy; Khan, Ghulam Jilany; Oanh, Ha Van; Hung, Ta Manh; Li, Hui-Jun; Li, Ping

2018-05-04

This study was designed to search for novel anti-cancer compounds from natural plants. The 70% ethanolic extract from the rizhomes of Cimicifuga dahurica (Turcz.) Maxim. (Ranunculaceae) was found to possess significant in vitro anti-proliferative effects on MCF-7 breast cancer cells. A phytochemical investigation using assay-guided fractionation of the ethanolic extract of C. dahurica resulted in the isolation of one new phenolic amide glycoside 3 , two new lignan glycosides 4 and 7 , one new 9,19-cycloartane triterpenoid glycoside 6 , and thirteen known constituents 1 , 2 , 5 , and 8 ⁻ 17 . The structures of 3 , 4 , 6 , and 7 were established using contemporary NMR methods and from their HRESIMS data. The anti-proliferative effects of isolated compounds were evaluated using the BrdU-proliferation kit. Five among the 17 isolated compounds showed significant anti-proliferative effects ( p ≤ 0.05), wherein compound 7 showed the most significant anti-proliferative and cell cycle arresting effect ( p ≤ 0.05) which followed a dose dependent manner. Western blot protein expression analysis showed a down expression of c-Myc and cyclin D1 which further elucidated the anti-proliferation mechanism of compound 7 while apoptotic effects were found in association with Bcl-2 family protein expression variations. Conclusively this study reports the isolation and identification of 17 compounds from C. dahurica , including four novel molecules, in addition to the fact that compound 7 possesses significant anti-proliferative and apoptotic effects in vitro that may require further exploration.

Proliferative verrucous leukoplakia; a critical appraisal of the diagnostic criteria

NARCIS (Netherlands)

Carrard, V.C.; Brouns, E.R.E.A.; van der Waal, I.

2013-01-01

Since its introduction in the literature in 1985, the term proliferative verrucous leukoplakia (PVL) has been the subject of an ongoing discussion with regard to its definition. Widespread or multifocal occurrence of oral leukoplakia is not just synonymous to PVL. In the present treatise the

Diagnostic value of ductogalactography and cytology in the proliferative changes of the mammary ducts

International Nuclear Information System (INIS)

Sessa, M.; Cerroni, L.; Bertolotti, A.

1991-01-01

Three hundred and thiyrty-six patients with nipple discharge and neither physical signs at breast examination nor pathological findings at mammography, were observed from 1984 to 1988 and studied by means of ductogalactography and cytology of discharge. Of this group, 76 patients (22%) underwent surgery and histology. In 65/76 cases proliferative pathologic conditions were demonstrated: 51 single/ multiple papillomas and 14 carcinomas. Ductogalactography suggested proliferative pathologic conditions in 59 cases and cytology of discharge showed blood in 44 patients, papillary clusters in 23, and atypical cells in 15 (both as single occurrences and in association). In cancer patients discharge appeared to be mostly spontaneous, monoductal and blood-stained. In papillomas, induced discharge was almost as frequent as spontaneous discharge, and milky discharge was also present. Ductogalactography confirmed its value in the diagnosis of proliferative pathologic conditions of the mammary ducts, being especially useful to detect carcinomas without palpable tumors. Cytology of discharge had poorer diagnostic significance

Proteomic analysis of the vitreous following experimental retinal detachment in rabbits

DEFF Research Database (Denmark)

Mandal, Nakul; Lewis, Geoffrey P.; Fisher, Steven K.

2015-01-01

of the vitreous following experimental retinal detachment using a comparative proteomic based approach. Materials and Methods. Retinal detachment was created in the right eyes of six New Zealand red pigmented rabbits. Sham surgery was undertaken in five other rabbits that were used as controls. After seven days......Purpose. The pathogenesis of rhegmatogenous retinal detachment (RRD) remains incompletely understood, with no clinically effective treatment for potentially severe complications such as photoreceptor cell death and proliferative vitreoretinopathy. Here we investigate the protein profile...... the eyes were enucleated and the vitreous was removed. The vitreous samples were evaluated with two-dimensional polyacrylamide gel electrophoresis and the differentially expressed proteins were identified with tandem mass spectrometry. Results. Ten protein spots were found to be at least twofold...

Amniocar as a proliferative medium for mesenchymal cells

Directory of Open Access Journals (Sweden)

V. V. Chestkov

2014-01-01

Full Text Available Objectives. To develop the Amniocar nutrient medium that contains fetal calf serum (FCS and growth factors cocktail for mass cultivation of human fibroblasts. To study proliferative activity of the medium on cultures of HUVEC cells of mesenchymal origin and mesenchymal stromal cells, as well as on cell culture of human amniotic fluid.Materials and methods. Determination of the rate of accumulation of the cellular mass and cell morphology in the course of cultivation of cells of various histogenesis in the Amniocar medium and nutrient medium that contains 10 % of FCS.Results. It has been demonstrated that the Amniocar medium is prevalent as compared to the standard DMEM medium with 10 % of FCS by 2 to 5 times for cultivation of skin fibroblasts, HUVEC, and mesenchymal stem cells. The Amniocar medium increased the quantity of endothelial cells that enter mitosis and maintained the culture of HUVEC cells with prolonged passaging in vitro. Clonal cultivation of human amniotic fluid cells in the Amniocar medium secured development of colonies of both fibroblast and epithelial type.Conclusions. Proliferative Amniocar medium is efficient for mass cultivation of various cells of mesenchymal origin and can be used for diagnostic purposes in medical genetics, oncology, etc.

Apoptotic and anti-proliferative effects of all-trans retinoic acid

International Nuclear Information System (INIS)

Zamora, Monica; Ortega, Juan Alberto; Alana, Lide; Vinas, Octavi; Mampel, Teresa

2006-01-01

We examined the apoptotic and anti-proliferative effects of all-trans retinoic acid (atRA) in HeLa cells. Our results demonstrated that HeLa cells were more sensitive to the anti-proliferative effects of atRA than to its apoptotic effects. Furthermore, we demonstrated that caspase inhibition attenuates cell death but does not alter the atRA-dependent reduction in cell proliferation, which suggests that atRA-induced apoptosis is independent of the arrest in cell proliferation. To check whether ANT proteins mediated these atRA effects, we transiently transfected cells with expression vectors encoding for individual ANT (adenine nucleotide translocase 1-3). Our results revealed that ANT1 and ANT3 over-expressing HeLa cells increased their atRA sensitivity. Thus, our results not only demonstrate the different functional activities of ANT isoforms, but also contribute to a better understanding of the properties of atRA as an anti-tumoral agent used in cancer therapy

Chemical Constituents from Cimicifuga dahurica and Their Anti-Proliferative Effects on MCF-7 Breast Cancer Cells

Directory of Open Access Journals (Sweden)

Chu Thi Thanh Huyen

2018-05-01

Full Text Available This study was designed to search for novel anti-cancer compounds from natural plants. The 70% ethanolic extract from the rizhomes of Cimicifuga dahurica (Turcz. Maxim. (Ranunculaceae was found to possess significant in vitro anti-proliferative effects on MCF-7 breast cancer cells. A phytochemical investigation using assay-guided fractionation of the ethanolic extract of C. dahurica resulted in the isolation of one new phenolic amide glycoside 3, two new lignan glycosides 4 and 7, one new 9,19-cycloartane triterpenoid glycoside 6, and thirteen known constituents 1, 2, 5, and 8–17. The structures of 3, 4, 6, and 7 were established using contemporary NMR methods and from their HRESIMS data. The anti-proliferative effects of isolated compounds were evaluated using the BrdU-proliferation kit. Five among the 17 isolated compounds showed significant anti-proliferative effects (p ≤ 0.05, wherein compound 7 showed the most significant anti-proliferative and cell cycle arresting effect (p ≤ 0.05 which followed a dose dependent manner. Western blot protein expression analysis showed a down expression of c-Myc and cyclin D1 which further elucidated the anti-proliferation mechanism of compound 7 while apoptotic effects were found in association with Bcl-2 family protein expression variations. Conclusively this study reports the isolation and identification of 17 compounds from C. dahurica, including four novel molecules, in addition to the fact that compound 7 possesses significant anti-proliferative and apoptotic effects in vitro that may require further exploration.

Macrophage Migration Inhibitory Factor Mediates Proliferative GN via CD74

Science.gov (United States)

Djudjaj, Sonja; Lue, Hongqi; Rong, Song; Papasotiriou, Marios; Klinkhammer, Barbara M.; Zok, Stephanie; Klaener, Ole; Braun, Gerald S.; Lindenmeyer, Maja T.; Cohen, Clemens D.; Bucala, Richard; Tittel, Andre P.; Kurts, Christian; Moeller, Marcus J.; Floege, Juergen; Ostendorf, Tammo

2016-01-01

Pathologic proliferation of mesangial and parietal epithelial cells (PECs) is a hallmark of various glomerulonephritides. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that mediates inflammation by engagement of a receptor complex involving the components CD74, CD44, CXCR2, and CXCR4. The proliferative effects of MIF may involve CD74 together with the coreceptor and PEC activation marker CD44. Herein, we analyzed the effects of local glomerular MIF/CD74/CD44 signaling in proliferative glomerulonephritides. MIF, CD74, and CD44 were upregulated in the glomeruli of patients and mice with proliferative glomerulonephritides. During disease, CD74 and CD44 were expressed de novo in PECs and colocalized in both PECs and mesangial cells. Stress stimuli induced MIF secretion from glomerular cells in vitro and in vivo, in particular from podocytes, and MIF stimulation induced proliferation of PECs and mesangial cells via CD74. In murine crescentic GN, Mif-deficient mice were almost completely protected from glomerular injury, the development of cellular crescents, and the activation and proliferation of PECs and mesangial cells, whereas wild-type mice were not. Bone marrow reconstitution studies showed that deficiency of both nonmyeloid and bone marrow–derived Mif reduced glomerular cell proliferation and injury. In contrast to wild-type mice, Cd74-deficient mice also were protected from glomerular injury and ensuing activation and proliferation of PECs and mesangial cells. Our data suggest a novel molecular mechanism and glomerular cell crosstalk by which local upregulation of MIF and its receptor complex CD74/CD44 mediate glomerular injury and pathologic proliferation in GN. PMID:26453615

Proliferative thyroid lesions in three diplodactylid geckos: Nephrurus amyae, Nephrurus levis, and Oedura marmorata.

Science.gov (United States)

Hadfield, Catherine A; Clayton, Leigh A; Clancy, Meredith M; Beck, Sarah E; Mangus, Lisa M; Montali, Richard J

2012-03-01

Over a 5-mo period, three diplodactylid geckos housed at the National Aquarium were diagnosed with proliferative thyroid lesions: a rough knob-tail gecko (Nephrurus amyae), a smooth knob-tail gecko (Nephrurus levis), and a marbled velvet gecko (Oedura marmorata). Clinical signs included an intraoral mass or ventral throat swelling (or both), oral bleeding, and weight loss. Both of the knob-tail geckos died. The histologic diagnosis for the rough knob-tail gecko was thyroid carcinoma with metastases to the liver and lungs, and thyroid carcinoma with no metastases was reported in the smooth knob-tail gecko. A thyroidectomy was performed on the marbled velvet gecko with a histologic diagnosis of adenomatous hyperplasia. Postoperative weight loss and bradycardia resolved following oral supplementation with levothyroxine. The animal is in normal health 10 mo post-surgery. Five other diplodactylid geckos in the collection remain unaffected, giving a 38% prevalence of proliferative thyroid lesions (3/8). The etiology remains undetermined. This is the first report of a cluster of proliferative thyroid lesions in geckos.

Evaluation of the anti-proliferative and cytostatic effect of Citrus sinensis (orange) fruit juice.

Science.gov (United States)

Chinedu, Enegide; Arome, David; Ameh, Solomon F; Ameh, Gift E

2014-09-01

This work has been designed to evaluate the anti-proliferative and cytostatic effects of Citrus sinensis (orange) fruit juice on rapidly proliferating cells. The study was carried out on the seeds of Sorghum bicolor for 72 h. The mean radicle length (mm) of the seeds was taken at 48 and 72 h. The result showed that when compared with the control, methotrexate, the standard drug showed a significant (P < 0.001) anti-proliferative effect throughout the experiment. The inhibition of the radicle growth was more after 72 h (87.42%). At a dose of 5% (v/v), the juice showed a slightly significant (P < 0.05) effect affect after 72 h; however, there was no significant effect at 48 h. The juice at doses of 10% and 20% (v/v) showed a highly significant (P < 0.001) anti-proliferative effect throughout the experiment; however, the percentage inhibitions were higher at 72 h. At 72 h, the percentage inhibition for juice at 10% (v/v) was 72.37% and at 20% (v/v) was 91.96%. The concentrations of 40% and 60% (v/v) showed cytostatic effects as no appreciable growth of the radicles of the seeds was observed throughout the experiment. The percentage inhibition for 40% (v/v) was 100% and 99.72% for 48 and 72 h, respectively, while that for the juice concentration of 60% (v/v) was 100% throughout the study. The experiment has shown that C. sinensis fruit juice has a potential for causing both anti-proliferative and cytostatic effects on fast proliferating cells and hence cancerous cells.

Protein metabolism of prolific ewes during late gestation and early lactation

NARCIS (Netherlands)

Sebek, L.B.J.

2001-01-01

Subject headings: protein / metabolism / ewes

Introduction of prolific crossbred ewes and a new protein evaluation system for ruminants, the DVE/OEB system, necessitate a reconsideration of ewe feeding strategies. The objective of this thesis is to investigate the amount

Neoplastic and proliferative disorders of the perinephric space

International Nuclear Information System (INIS)

Heller, M.T.; Haarer, K.A.; Thomas, E.; Thaete, F.L.

2012-01-01

The perinephric space is a well-marginated central compartment of the retroperitoneum, located between the anterior and posterior pararenal spaces. Various neoplastic and proliferative disorders can affect the perinephric space, and there is a wide array of imaging findings. Although many perinephric lesions may extend directly from the kidney and adrenal gland, other lesions occur in the perinephric space due to haematogenous spread, as part of a systemic disease, or by extension from an adjacent retroperitoneal compartment. Imaging plays a pivotal role in the diagnosis of perinephric diseases, as many of the disease processes affecting this space will not result in clinical signs or symptoms until the disease is at an advanced stage. Despite the often shared non-specific clinical and imaging findings among these disease processes, application of a categorical differential diagnosis based on the imaging characteristics will serve to narrow the differential diagnosis and direct further evaluation and treatment. In this article, the lesions have been categorized as soft-tissue rind [nephroblastomatosis, fibrosis, Erdheim–Chester disease (ECD), extramedullary haematopoiesis, lymphoma, infiltrating metastases], focal solid lesions (extension of renal or adrenal malignancies, melanoma metastases, treated lymphoma), fat-containing lesions (angiomyolipoma, liposarcoma, myelolipoma), and cystic lesions (lymphangiomas, abscesses). The aim of this article is to demonstrate and describe the key imaging features of several neoplastic and proliferative disorders that affect the perinephric space.

To report a case of unilateral proliferative retinopathy following noncerebral malaria with Plasmodium falciparum in Southern India

Directory of Open Access Journals (Sweden)

Aditya Verma

2015-01-01

Full Text Available The retinopathy in association with malaria fever described so far includes retinal hemorrhages, vessel changes, retinal discoloration/whitening and papilledema. Malaria retinopathy has been mostly described in severe cases, associated with Plasmodium falciparum, correlating the patho-physiology of retinal and cerebral manifestations. We report an unusual case of proliferative retinopathy as a manifestation of malaria fever, caused by P. falciparum with no cerebral involvement. The patient had features of unilateral retinal vascular occlusion with proliferative changes and vitreous hemorrhage. To the best of our knowledge, such a case has never been reported so far in the literature. This report highlights the possible occurrence of severe proliferative changes associated with malaria fever, which if diagnosed early can prevent possible blindness.

Synergy among rat T cells in the proliferative response to alloantigen

International Nuclear Information System (INIS)

Wright, P.W.; Loop, S.M.; Bernstein, I.D.

1979-01-01

A synergistic interaction in the proliferative response to alloantigen is described for mixtures of rat thymus and lymph node cells. The optimal conditions for synergy are quantitatively defined. Regression analysis of the slope of the dose-response curve has been utilized to estimate the degree of interaction in thymus--lymph node cell mixtures. The slope of the response of cell mixtures was noted to be significantly greater than the slope for the response of lympth node cells alone. Irradiation was shown to have a differential effect on the response of thymus and lymph node cells in mixtures. Irradiated thymus cells retained the capacity for synergy in mixtures, whereas irradiated lymph node cells did not. Additional studies have demonstrated that both de novo protein synthesis and specific antigen recognition by both responding cell populations in mixtures was required for maximal synergy. These studies demonstrate that synergy cannot be explained as an artifact of altered cell density in vitro. They establish that thymus cells and lymph node cells represent distinct subsets which manifest qualitatively different functions in the proliferative response to alloantigen. Thymus cells can respond directly to alloantigen by proliferation but also have the capacity to amplify the proliferative response of lymph node cells, a capacity which is resistant to X irradiation but requires recognition of alloantigen and de novo protein synthesis. Lymph node cells may similarly respond by proliferation to alloantigen but lack the amplifier activity of thymus cells. Synergy for rat lymphoidcells, like mouse lymphoid cells, has been shown to involve an interaction of thymus-derived lymphocytes

Rhegmatogenous retinal detachment and uveitis.

Science.gov (United States)

Kerkhoff, Frank T; Lamberts, Querin J; van den Biesen, Pieter R; Rothova, Aniki

2003-02-01

To evaluate the frequency, high-risk factors, and visual prognosis of rhegmatogenous retinal detachment (RRD) in patients with uveitis. Retrospective case-control study. We included 1387 consecutive patients with uveitis who consulted our uveitis clinic from January 1990 through December 1997 of whom 43 patients (46 eyes) with RRD were identified. The retinal detachment (RD) controls were 212 consecutive patients with RRD (221 eyes, first occurrence of RD, not associated with uveitis) who were admitted for surgery in the period from April 1999 to April 2000. The uveitis control group consisted of 150 age-matched patients (210 eyes) selected from the entire uveitis series. Retrospective analysis of clinical data. The presence of RRD and eventual risk factors for RRD, such as myopia, retinal lattice degeneration, prior intraocular surgery, anatomic location of uveitis, its specific diagnosis, and clinical manifestations. Furthermore, the surgical and nonsurgical outcomes of RRD, as well as the results of various treatment regimens, were analyzed. RRD was identified in 3.1% of the patients with uveitis. RRD was most frequently associated with panuveitis (6.6%). RRD was associated more frequently with infectious (7.6%) than noninfectious uveitis (2.1%). At the onset of RRD, uveitis was active in most (46%) affected eyes. Proliferative vitreoretinopathy was present in 30% of the uveitic RRD eyes at presentation in contrast to 12% of the RRD control eyes. In uveitic RRD, the retina was reattached in 59% of eyes with a single operation; the final anatomic reattachment rate was 88%. Finally, a visual acuity of less than 20/200 was present in 71% of the uveitic RRD eyes, 10% of which had no light perception. We discovered a high prevalence of RRD in patients with active panuveitis and infectious uveitis and document that uveitis in itself is a risk factor for the development of RRD. The visual prognosis of RRD in uveitis was poor because of the uveitis itself and the

Esculetin exerts anti-proliferative effects against non-small-cell lung carcinoma by suppressing specificity protein 1 in vitro.

Science.gov (United States)

Lee, Ra H; Jeon, Young-Joo; Cho, Jin H; Jang, Jeong-Yun; Kong, Il-Keun; Kim, Seok-Ho; Kim, MinSeok S; Chung, Hak-Jae; Oh, Keon B; Park, Seon-Min; Shin, Jae-Cheon; Seo, Jae-Min; Ko, Sungho; Shim, Jung-Hyun; Chae, Jung-Il

2017-01-01

Esculetin, a coumarin derivative, is a phenolic compound isolated from Artemisia capillaris, Citrus limonia, and Euphorbia lathyris. Although it has been reported to have anti-inflammatory, anti-oxidant, and anti-proliferative activities in several human cancers, its anti-proliferative activity against non-small-cell lung carcinoma (NSCLC) and the molecular mechanisms involved have not been adequately elucidated. In this study, we used two NSCLC cell lines (NCI-H358 and NCI-H1299) to investigate the anti-proliferative activity and apoptotic effect of esculetin. Our data showed that esculetin-treated cells exhibited reduced proliferation and apoptotic cell morphologies. Intriguingly, the transcription factor specificity protein 1 (Sp1) was significantly suppressed by esculetin in a dose- and time-dependent manner. Furthermore, the levels of p27 and p21, two key regulators of the cell cycle, were up-regulated by the esculetin-mediated down-regulation of Sp1; the level of a third cell-cycle regulator, survivin, was decreased, resulting in caspase-dependent apoptosis. Therefore, we conclude that esculetin could be a potent anti-proliferative agent in patients with NSCLC.

Changes in the Proliferative Program Limit Astrocyte Homeostasis in the Aged Post-Traumatic Murine Cerebral Cortex.

Science.gov (United States)

Heimann, Gábor; Canhos, Luisa L; Frik, Jesica; Jäger, Gabriele; Lepko, Tjasa; Ninkovic, Jovica; Götz, Magdalena; Sirko, Swetlana

2017-08-01

Aging leads to adverse outcomes after traumatic brain injury. The mechanisms underlying these defects, however, are not yet clear. In this study, we found that astrocytes in the aged post-traumatic cerebral cortex develop a significantly reduced proliferative response, resulting in reduced astrocyte numbers in the penumbra. Moreover, experiments of reactive astrocytes in vitro reveal that their diminished proliferation is due to an age-related switch in the division mode with reduced cell-cycle re-entry rather than changes in cell-cycle length. Notably, reactive astrocytes in vivo and in vitro become refractory to stimuli increasing their proliferation during aging, such as Sonic hedgehog signaling. These data demonstrate for the first time that age-dependent, most likely intrinsic changes in the proliferative program of reactive astrocytes result in their severely hampered proliferative response to traumatic injury thereby affecting astrocyte homeostasis. © The Author 2017. Published by Oxford University Press.

Daphne striata Tratt. and D. mezereum L.: a study of anti-proliferative activity towards human cancer cells and antioxidant properties.

Science.gov (United States)

Tundis, Rosa; Loizzo, Monica R; Bonesi, Marco; Peruzzi, Lorenzo; Efferth, Thomas

2018-02-12

In this study, we investigated for the first time the anti-proliferative and antioxidant properties of D. mezereum and D. striata. The aerial parts were extracted by maceration with n-hexane, dichloromethane, and methanol. MPLC, GC, and GC-MS were used for the phytochemical study. The anti-proliferative activity was tested against MCF-7, A549, LNCaP, ACHN, and C32 cancer human cells. The antioxidant activity was measured by employing β-carotene bleaching, ABTS, DPPH, and FRAP tests. The Relative Antioxidant Capacity Index (RACI) was applied from the perspective of statistics. D. mezereum dichloromethane extract showed a remarkable anti-proliferative with an IC 50 of 6.08 μg/mL against LNCaP cells. Experimental data indicate that Daphne species have interesting anti-proliferative and antioxidant properties that deserve more investigations to develop novel antineoplastic drugs.

Protein oxidation and degradation during proliferative senescence of human MRC-5 fibroblasts.

Science.gov (United States)

Sitte, N; Merker, K; von Zglinicki, T; Grune, T

2000-03-01

One of the highlights of age-related changes of cellular metabolism is the accumulation of oxidized proteins. The aging process on a cellular level can be treated either as the ongoing proliferation until a certain number of cell divisions is reached (the Hayflick limit) or as the aging of nondividing cells, that is, the age-related changes in cells without proliferation. The present investigation was undertaken to reveal the changes in protein turnover, proteasome activity, and protein oxidation status during proliferative senescence. We were able to demonstrate that the activity of the cytosolic proteasomal system declines dramatically during the proliferative senescence of human MRC-5 fibroblasts. Regardless of the loss in activity, it could be demonstrated that there are no changes in the transcription and translation of proteasomal subunits. This decline in proteasome activity was accompanied by an increased concentration of oxidized proteins. Cells at higher proliferation stages were no longer able to respond with increased degradation of endogenous [(35)S]-Met-radiolabeled proteins after hydrogen peroxide- or quinone-induced oxidative stress. It could be demonstrated that oxidized proteins in senescent human MRC-5 fibroblasts are not as quickly removed as they are in young cells. Therefore, our study demonstrates that the accumulation of oxidized proteins and decline in protein turnover and activity of the proteasomal system are not only a process of postmitotic aging but also occur during proliferative senescence and result in an increased half-life of oxidized proteins.

Immediate and Midterm Cardiac Remodeling After Surgical Pulmonary Valve Replacement in Adults With Repaired Tetralogy of Fallot: A Prospective Cardiovascular Magnetic Resonance and Clinical Study.

Science.gov (United States)

Heng, Ee Ling; Gatzoulis, Michael A; Uebing, Anselm; Sethia, Babulal; Uemura, Hideki; Smith, Gillian C; Diller, Gerhard-Paul; McCarthy, Karen P; Ho, Siew Yen; Li, Wei; Wright, Piers; Spadotto, Veronica; Kilner, Philip J; Oldershaw, Paul; Pennell, Dudley J; Shore, Darryl F; Babu-Narayan, Sonya V

2017-10-31

Pulmonary valve replacement (PVR) in patients with repaired tetralogy of Fallot provides symptomatic benefit and right ventricular (RV) volume reduction. However, data on the rate of ventricular structural and functional adaptation are scarce. We aimed to assess immediate and midterm post-PVR changes and predictors of reverse remoeling. Fifty-seven patients with repaired tetralogy of Fallot (age ≥16 y; mean age, 35.8±10.1 y; 38 male) undergoing PVR were prospectively recruited for cardiovascular magnetic resonance performed before PVR (pPVR), immediately after PVR (median, 6 d), and midterm after PVR (mPVR; median, 3 y). There were immediate and midterm reductions in indexed RV end-diastolic volumes and RV end-systolic volumes (RVESVi) (indexed RV end-diastolic volume pPVR versus immediately after PVR versus mPVR, 156.1±41.9 versus 104.9±28.4 versus 104.2±34.4 mL/m 2 ; RVESVi pPVR versus immediately after PVR versus mPVR, 74.9±26.2 versus 57.4±22.7 versus 50.5±21.7 mL/m 2 ; P <0.01). Normal postoperative diastolic and systolic RV volumes (the primary end point) achieved in 70% of patients were predicted by a preoperative indexed RV end-diastolic volume ≤158 mL/m 2 and RVESVi ≤82 mL/m 2 . RVESVi showed a progressive decrease from baseline to immediate to midterm follow-up, indicating ongoing intrinsic RV functional improvement after PVR. Left ventricular ejection fraction improved (pPVR versus mPVR, 59.4±7.6% versus 61.9±6.8%; P <0.01), and right atrial reverse remodeling occurred (pPVR versus mPVR, 15.2±3.4 versus 13.8±3.6 cm 2 /m 2 ; P <0.01). Larger preoperative RV outflow tract scar was associated with a smaller improvement in post-PVR RV/left ventricular ejection fraction. RV ejection fraction and peak oxygen uptake predicted mortality ( P =0.03) over a median of 9.5 years of follow-up. Significant right heart structural reverse remodeling takes place immediately after PVR, followed by a continuing process of further biological remodeling

The Partisan Trajectory of the American Pro-Life Movement: How a Liberal Catholic Campaign Became a Conservative Evangelical Cause

Directory of Open Access Journals (Sweden)

Daniel K. Williams

2015-04-01

Full Text Available This article employs a historical analysis of the religious composition of the pro-life movement to explain why the partisan identity of the movement shifted from the left to the right between the late 1960s and the 1980s. Many of the Catholics who formed the first anti-abortion organizations in the late 1960s were liberal Democrats who viewed their campaign to save the unborn as a rights-based movement that was fully in keeping with the principles of New Deal and Great Society liberalism, but when evangelical Protestants joined the movement in the late 1970s, they reframed the pro-life cause as a politically conservative campaign linked not to the ideology of human rights but to the politics of moral order and “family values.” This article explains why the Catholic effort to build a pro-life coalition of liberal Democrats failed after Roe v. Wade, why evangelicals became interested in the antiabortion movement, and why the evangelicals succeeded in their effort to rebrand the pro-life campaign as a conservative cause.

ROLE OF THE MORPHOMETRIC PARAMETERS OF INTRATUMORAL MICROVESSELS AND THE PROLIFERATIVE ACTIVITY OF TUMOR CELLS IN RENAL CELL CARCINOMA

Directory of Open Access Journals (Sweden)

N. A. Gorban

2014-08-01

Full Text Available Tumor cell proliferation and angiogenesis are essential factors for tumor growth, progression, and metastasis.Objective: to assess the relationship between the values of proliferative activity and the morphometric parameters of intratumoral microvessels in metastatic and localized carcinomas of the kidney.Materials and methods. Surgical specimens taken from 54 patients (32 men and 22 women aged 26 to 69 years (mean age 55 ± 1.5 years with the verified diagnosis of clear-cell renal cell carcinoma (RCC were studied.Conclusion. Proliferative activity and angioarchitectonics are an important biological characteristic of a tumor of unequal clinical value in RCC. Metastatic carcinoma has a higher proliferative activity and a low tumor vascularization than those of localized carcinoma.

Heme oxygenase is not involved in the anti-proliferative effects of statins on pancreatic cancer cells

International Nuclear Information System (INIS)

Vanova, K.; Boukalova, S.; Gbelcova, H.; Muchova, L.; Neuzil, J.; Gurlich, R.; Ruml, T.; Vitek, L.

2016-01-01

Pancreatic cancer is recognized as one of the most fatal tumors due to its aggressiveness and resistance to therapy. Statins were previously shown to inhibit the proliferation of cancer cells via various signaling pathways. In healthy tissues, statins activate the heme oxygenase pathway, nevertheless the role of heme oxygenase in pancreatic cancer is still controversial. The aim of this study was to evaluate, whether anti-proliferative effects of statins in pancreatic cancer cells are mediated via the heme oxygenase pathway. In vitro effects of various statins and hemin, a heme oxygenase inducer, on cell proliferation were evaluated in PA-TU-8902, MiaPaCa-2 and BxPC-3 human pancreatic cancer cell lines. The effect of statins on heme oxygenase activity was assessed and heme oxygenase-silenced cells were used for pancreatic cancer cell proliferation studies. Cell death rate and reactive oxygen species production were measured in PA-TU-8902 cells, followed by evaluation of the effect of cerivastatin on GFP-K-Ras trafficking and expression of markers of invasiveness, osteopontin (SPP1) and SOX2. While simvastatin and cerivastatin displayed major anti-proliferative properties in all cell lines tested, pravastatin did not affect the cell growth at all. Strong anti-proliferative effect was observed also for hemin. Co-treatment of cerivastatin and hemin increased anti-proliferative potential of these agents, via increased production of reactive oxygen species and cell death compared to individual treatment. Heme oxygenase silencing did not prevent pancreatic cancer cells from the tumor-suppressive effect of cerivastatin or hemin. Cerivastatin, but not pravastatin, protected Ras protein from trafficking to the cell membrane and significantly reduced expressions of SPP1 (p < 0.05) and SOX2 (p < 0.01). Anti-proliferative effects of statins and hemin on human pancreatic cancer cell lines do not seem to be related to the heme oxygenase pathway. While hemin triggers reactive

Proliferative verrucous leukoplakia: an aggressive form of oral leukoplakia.

Science.gov (United States)

Shopper, Thomas P; Brannon, Robert B; Stalker, William H

2004-01-01

Proliferative verrucous leukoplakia (PVL) is an aggressive form of oral leukoplakia that is persistent, often multifocal, and refractory to treatment with a high risk of recurrence and malignant transformation. This article describes the clinical aspects and histologic features of a case that demonstrated the typical behavior pattern in a long-standing, persistent lesion of PVL of the mandibular gingiva and that ultimately developed into squamous cell carcinoma. Prognosis is poor for this seemingly harmless-appearing white lesion of the oral mucosa.

Comparison of valvar and right ventricular function following transcatheter and surgical pulmonary valve replacement.

Science.gov (United States)

Li, Wendy F; Pollard, Heidi; Karimi, Mohsen; Asnes, Jeremy D; Hellenbrand, William E; Shabanova, Veronika; Weismann, Constance G

2018-01-01

Trans-catheter (TC) pulmonary valve replacement (PVR) has become common practice for patients with right ventricular outflow tract obstruction (RVOTO) and/or pulmonic insufficiency (PI). Our aim was to compare PVR and right ventricular (RV) function of patients who received TC vs surgical PVR. Retrospective review of echocardiograms obtained at three time points: before, immediately after PVR, and most recent. Sixty-two patients (median age 19 years, median follow-up 25 months) following TC (N = 32) or surgical (N = 30) PVR at Yale-New Haven Hospital were included. Pulmonary valve and right ventricular function before, immediately after, and most recently after PVR. At baseline, the TC group had predominant RVOTO (74% vs 10%, P function was good throughout. At last follow-up, the TC group had preserved valve function, but the surgical group did not (moderate RVOTO: 6% vs 41%, P mild PI: 0% vs 24%, P = .003). Patients younger than 17 years at surgical PVR had the highest risk of developing PVR dysfunction, while PVR function in follow-up was similar in adults. Looking at RV size and function, both groups had a decline in RV size following PVR. However, while RV function remained stable in the TC group, there was a transient postoperative decline in the surgical group. TC PVR in patients age function in follow-up compared to surgical valves. There was a transient decline in RV function following surgical but not TC PVR. TC PVR should therefore be the first choice in children who are considered for PVR, whenever possible. © 2017 Wiley Periodicals, Inc.

In vitro anti-proliferative and anti-inflammatory activity of leaf and fruit extracts from Vaccinium bracteatum Thunb

OpenAIRE

Landa, P. (Přemysl); Skálová, L.; Boušová, I.; Kutil, Z. (Zsófia); Langhansová, L. (Lenka); Lou, J.D.; Vaněk, T. (Tomáš)

2014-01-01

The aim of this study was to evaluate in vitro anti-proliferative (tested on MCF-7, MDA-MB-231, and MCF-10A cell lines) and anti-inflammatory (evaluated as inhibition of prostaglandin E2 synthesis catalyzed by cyclooxygenase-2) effect of various extracts from Vaccinium bracteatum leaves and fruits. The highest anti-proliferative effect possessed leaf dichloromethane extract with IC50 values ranging from 93 to 198 mug/mL. In the case of cyclooxygenase-2 inhibition, n-hexane, dichloromethane, a...

Proliferative reactive gliosis is compatible with glial metabolic support and neuronal function

Directory of Open Access Journals (Sweden)

Fero Matthew

2011-10-01

Full Text Available Abstract Background The response of mammalian glial cells to chronic degeneration and trauma is hypothesized to be incompatible with support of neuronal function in the central nervous system (CNS and retina. To test this hypothesis, we developed an inducible model of proliferative reactive gliosis in the absence of degenerative stimuli by genetically inactivating the cyclin-dependent kinase inhibitor p27Kip1 (p27 or Cdkn1b in the adult mouse and determined the outcome on retinal structure and function. Results p27-deficient Müller glia reentered the cell cycle, underwent aberrant migration, and enhanced their expression of intermediate filament proteins, all of which are characteristics of Müller glia in a reactive state. Surprisingly, neuroglial interactions, retinal electrophysiology, and visual acuity were normal. Conclusion The benign outcome of proliferative reactive Müller gliosis suggests that reactive glia display context-dependent, graded and dynamic phenotypes and that reactivity in itself is not necessarily detrimental to neuronal function.

Synthesis and Anti-Proliferative Effects of Mono- and Bis-Purinomimetics Targeting Kinases

Directory of Open Access Journals (Sweden)

Andrea Bistrović

2017-11-01

Full Text Available A series of mono-pyrrolo[2,3-d]pyrimidines 4a–4k, unsymmetrical bis-purine isosteres 5a–5e and symmetrical bis-pyrrolo[2,3-d]pyrimidines 6a and 6b connected via di(1,2,3-triazolylphenyl linker were synthesized by click chemistry. Whereas mono- 4g and bis-pseudopurine 5e showed selective inhibitory activities on cervical carcinoma (HeLa cells, bis-pyrrolo[2,3-d]pyrimidine 6b exhibited potent and selective anti-proliferative effect in the nanomolar range on pancreatic carcinoma (CFPAC-1 cells. Among these, compound 6b induced a significant reduction in the expression level of CDK9 (cyclin-dependent kinase 9/cyclin T1 in CFPAC-1 cells concomitant with attenuation of proliferative signaling mediated by c-Raf (rapidly accelerated fibrosarcoma and p38 MAP (mitogen-activated protein kinases. Our findings encourage further development of novel structurally related analog of 6b to obtain more selective anticancer agent for treating pancreatic cancer.

Phytochemical properties and anti-proliferative activity of Olea europaea L. leaf extracts against pancreatic cancer cells.

Science.gov (United States)

Goldsmith, Chloe D; Vuong, Quan V; Sadeqzadeh, Elham; Stathopoulos, Costas E; Roach, Paul D; Scarlett, Christopher J

2015-07-17

Olea europaea L. leaves are an agricultural waste product with a high concentration of phenolic compounds; especially oleuropein. Oleuropein has been shown to exhibit anti-proliferative activity against a number of cancer types. However, they have not been tested against pancreatic cancer, the fifth leading cause of cancer related death in Western countries. Therefore, water, 50% ethanol and 50% methanol extracts of Corregiola and Frantoio variety Olea europaea L. leaves were investigated for their total phenolic compounds, total flavonoids and oleuropein content, antioxidant capacity and anti-proliferative activity against MiaPaCa-2 pancreatic cancer cells. The extracts only had slight differences in their phytochemical properties, and at 100 and 200 μg/mL, all decreased the viability of the pancreatic cancer cells relative to controls. At 50 μg/mL, the water extract from the Corregiola leaves exhibited the highest anti-proliferative activity with the effect possibly due to early eluting HPLC peaks. For this reason, olive leaf extracts warrant further investigation into their potential anti-pancreatic cancer benefits.

History of Psychology Publish and Perish: Psychology's Most Prolific Authors Are Not Always the Ones We Remember.

Science.gov (United States)

Green, Christopher D

2017-01-01

What is the relationship between being highly prolific in the realm of publication and being remembered as a great psychologist of the past? In this study, the PsycINFO database was used to identify the historical figures who wrote the most journal articles during the half-century from 1890 to 1939. Although a number of the 10 most prolific authors are widely remembered for their influence on the discipline today-E. L. Thorndike, Karl Pearson, E. B. Titchener, Henri Pi6ron-the majority are mostly forgotten. The data were also separated into the 5 distinct decades. Once again, a mixture of eminent and obscure individuals made appearances. Most striking, perhaps, was the great increase in articles published over the course of the half-century-approximately doubling each decade-and the enormous turnover in who was most prolific, decade over decade. In total, 100 distinct individuals appeared across just 5 lists of about 25 names each.

Cytological Study of Breast Carcinoma Before and After Oncotherapy with Special Reference to Morphometry and Proliferative Activity.

Science.gov (United States)

Koley, Sananda; Chakrabarti, Srabani; Pathak, Swapan; Manna, Asim Kumar; Basu, Siddhartha

2015-12-01

Our study was done to assess the cytological changes due to oncotherapy in breast carcinoma especially on morphometry and proliferative activity. Cytological aspirates were collected from a total of 32 cases of invasive ductal carcinoma both before and after oncotherapy. Morphometry was done on the stained cytological smears to assess the different morphological parameters of cell dimension by using the ocular morphometer and the software AutoCAD 2007. Staining was done with Ki-67 and proliferating cell nuclear antigen (PCNA) as proliferative markers. Different morphological parameters were compared before and after oncotherapy by unpaired Student's t test. Statistically significant differences were found in morphometric parameters, e.g., mean nuclear diameter, mean nuclear area, mean cell diameter, and mean cell area, and in the expression of proliferative markers (Ki-67 and PCNA). Statistical analysis was done by obtaining p values. There are statistically significant differences between morphological parameter of breast carcinoma cells before and after oncotherapy.

Ocular pulse amplitude after panretinal photocoagulation in normotensive eyes with proliferative diabetic retinopathy.

Science.gov (United States)

Bozic, Marija M; Karadzic, Jelena B; Kovacevic, Igor M; Marjanovic, Ivan S

2017-06-26

To assess the effect of panretinal laser photocoagulation on ocular pulse amplitude (OPA) in normotensive eyes with proliferative diabetic retinopathy. Prospectively, we performed unilateral argon laser panretinal photocoagulation (PRP) in 30 patients with diabetes mellitus type II and previously untreated bilateral proliferative diabetic retinopathy. Before and 7 and 30 days after the treatment, OPA was measured using dynamic contour tonometer. Compared with the untreated contralateral eyes, laser photocoagulation led to a reduction of OPA. Ocular pulse amplitude did not significantly differ in photocoagulated eyes 7 days after the treatment, but there was a significant difference in OPA 30 days after the treatment. The decrease in OPA values was 15% 7 days after PRP and 40% 30 days after PRP. Ocular pulse amplitude reduction after PRP indirectly informs us about choriocapillary closure, already reported in previous studies.

COMPARISONS BETWEEN THE NON-PROLIFERATIVE AND PROLIFERATIVE THERAPY IN FIBROCYSTIC MASTOSIS.

Science.gov (United States)

Carauleanu, A; Socolov, R; Rugina, V; Gabia, O; Carauleanu, Daniela Mihaela; Lupascu, Ivona Anghlcelache; Socolov, Demetra

2016-01-01

Fibrocystic mastosis (FCM) is the most frequent benign breast lesion. Most treatments for fibrocystic mastosis are: hormonl, with beneficial results and non-hormonal, with fluctuating results. A number of 210 cases were studied, which were divided into 7 groups. The study lasted for 9 months and it was carried out on the basis of a personal examination sheet. The following were monitored: age groups, mastodynia, reducing breast nodules, a significant reduction in the volume of the mastosic cysts, reducion of the fibrous tissue, medication tolerance. Mastodynia has declined by 90% in the cases treated with Tamoxifen and Danazol, by 70% in the case of Lynestrenol and Bromocriptine, by 50% in the 15 patients who were given Utrogestan. Knowing the advantages and disadvantages of drugs (contraindications, side effects), age category, breast pain reduction, antiproliferative activity, tolerability, relapse allow us to assess the benefit-risk. Even in those circumstances that remained incompletely clarified for objective reasons, related to the inaccurate/incorrect reporting by the patients, there is a significant difference (p < 0.05) between the frequency of relapses following the treatment with Tamoxifen and the other categories of drugs who were administered. Our study shows that in the groups that were administered Logest, Utrogestan and Bromocriptine, only antalgic effects were achieved (disappearance or only decrease of mastodynia) and no anti-proliferative effects were obtained. Basically, hormone treatment should be made based on a histopathological examination.

Detection of Lawsonia intracellularis in the tonsils of pigs with proliferative enteropathy

DEFF Research Database (Denmark)

Jensen, Tim Kåre; Møller, Kristian; Lindecrona, R. H.

2000-01-01

to necropsy but not in four pigs with moderate PE lesions. However, L. intracellularis was detected in the tonsils of 4/9 pigs with PE complicated with necroses and in 4/4 pigs with proliferative haemorrhagic enteropathy in which L. intracellularis antigen also was demonstrated in tonsillar macrophages...

Transcatheter versus surgical valve replacement for a failed pulmonary homograft in the Ross population.

Science.gov (United States)

Alassas, Khadija; Mohty, Dania; Clavel, Marie Annick; Husain, Aysha; Hijji, Talal; Aljoufan, Mansour; Alhalees, Zohair; Fadel, Bahaa M

2018-04-01

Patients who undergo the Ross procedure are at increased risk of pulmonary valve (PV) homograft dysfunction. For those who require reintervention on the homograft, transcatheter PV replacement (tPVR) provides a less invasive therapeutic option than surgical PVR (sPVR). We examined the outcomes following tPVR versus sPVR in a cohort of patients who underwent the Ross procedure. We performed a retrospective analysis of Ross patients age ≥14 years who underwent tPVR (n = 47) or sPVR (n = 41) at our institution. The patients' clinical and echocardiographic data were reviewed. Baseline parameters, including demographic data and left ventricular and right ventricular (RV) systolic function, were similar in the 2 groups. The mean follow-up was 56 ± 24 months for the tPVR group and 89 ± 46 months for the sPVR group (P Ross patients who require reintervention on the PV homograft, both tPVR and sPVR provide low procedural mortality and comparable midterm outcome with no significant difference in mortality or PV reintervention. However, IE is more common following tPVR. A larger randomized study is needed to determine the role of each procedure in patient management. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Early versus late pulmonary valve replacement in patients with transannular patch-repaired tetralogy of Fallot.

Science.gov (United States)

Dobbels, Bieke; Herregods, Marie-Christine; Troost, Els; Van De Bruaene, Alexander; Rega, Filip; Budts, Werner; De Meester, Pieter

2017-09-01

Although the effects of pulmonary regurgitation after tetralogy of Fallot repair are detrimental, timing of pulmonary valve replacement (PVR) is unclear. Our goal was to evaluate the midterm efficacy and safety of early PVR. Patients with tetralogy of Fallot who underwent repair from 1962 to 2015 were included from the local database. Statistical analyses compared patients who underwent early PVR (age ≤16 years), late PVR and no PVR. The timing of the intervention was compared for efficacy-all-cause mortality and the combined end-point of all-cause mortality, ventricular tachycardia and defibrillator implantation-and for safety-the combined end-point of 1-year postoperative mortality after PVR, endocarditis and reintervention. Echocardiographic and electrocardiographic data at the last follow-up examination were compared across the 3 groups. Two hundred seventy-three patients (age 21 ± 5 years; 52% female) were included. The mean follow-up was 24 (95% confidence interval 22.7-26.2) years; the observed median was 21 years (interquartile range 11-31). No significant difference in survival was found between the early PVR (n = 106; 39%), the late PVR (n = 47; 17%) and the no PVR groups (n = 120; 44%) (P = 0.990). No significant difference in the combined efficacy end-point was noted between patients who underwent early PVR compared with patients who underwent late PVR (P = 0.247). Worse event-free survival for the 3-point safety end-point was observed after early PVR (P < 0.001). Right ventricular morphology (P < 0.001) and function (P < 0.001) were better preserved in the patient group that underwent PVR before the age of 16 years. As expected, PVR-related morbidity was higher in patients who underwent early PVR but the midterm outcome was similar. Nevertheless, better preservation of right ventricular morphology and function in the early PVR group might result in better long-term survival. © The Author 2017. Published by Oxford

Proliferative and anti-proliferative effects of dietary levels of phytoestrogens in rat pituitary GH3/B6/F10 cells - the involvement of rapidly activated kinases and caspases

International Nuclear Information System (INIS)

Jeng, Yow-Jiun; Watson, Cheryl S

2009-01-01

Phytoestogens are a group of lipophillic plant compounds that can have estrogenic effects in animals; both tumorigenic and anti-tumorigenic effects have been reported. Prolactin-secreting adenomas are the most prevalent form of pituitary tumors in humans and have been linked to estrogen exposures. We examined the proliferative effects of phytoestrogens on a rat pituitary tumor cell line, GH 3 /B 6 /F 10 , originally subcloned from GH 3 cells based on its ability to express high levels of the membrane estrogen receptor-α. We measured the proliferative effects of these phytoestrogens using crystal violet staining, the activation of several mitogen-activated protein kinases (MAPKs) and their downstream targets via a quantitative plate immunoassay, and caspase enzymatic activities. Four phytoestrogens (coumestrol, daidzein, genistein, and trans-resveratrol) were studied over wide concentration ranges. Except trans-resveratrol, all phytoestrogens increased GH 3 /B 6 /F 10 cell proliferation at some concentration relevant to dietary levels. All four phytoestrogens attenuated the proliferative effects of estradiol when administered simultaneously. All phytoestrogens elicited MAPK and downstream target activations, but with time course patterns that often differed from that of estradiol and each other. Using selective antagonists, we determined that MAPKs play a role in the ability of these phytoestrogens to elicit these responses. In addition, except for trans-resveratrol, a serum removal-induced extrinsic apoptotic pathway was blocked by these phytoestrogens. Phytoestrogens can block physiological estrogen-induced tumor cell growth in vitro and can also stimulate growth at high dietary concentrations in the absence of endogenous estrogens; these actions are correlated with slightly different signaling response patterns. Consumption of these compounds should be considered in strategies to control endocrine tumor cell growth, such as in the pituitary

T-cell proliferative responses following sepsis in neonatal rats.

Science.gov (United States)

Dallal, Ousama; Ravindranath, Thyyar M; Choudhry, Mashkoor A; Kohn, Annamarie; Muraskas, Jonathan K; Namak, Shahla Y; Alattar, Mohammad H; Sayeed, Mohammed M

2003-01-01

Both experimental and clinical evidence suggest a suppression of T-cell function in burn and sepsis. The objective of the present study was to evaluate splenocyte and purified T-cell proliferative response and IL-2 production in septic neonatal rats. We also examined if alterations in T-cell proliferation and IL-2 production in neonatal sepsis is due to elevation in PGE2. PGE2 is known to play a significant role in T-cell suppression during sepsis in adults. Sepsis was induced in 15-day-old neonatal Sprague-Dawley rats by implanting 0.1 cm3 of fecal pellet impregnated with Escherichia coli (50 CFU) and Bacteroides fragilis (10(3) CFU). Animals receiving fecal pellets without the bacteria were designated as sterile. A group of septic and sterile rats were treated with PGE2 synthesis inhibitors, NS398 and resveratrol. These treatments of animals allowed us to evaluate the role of PGE2 in T-cell suppression during neonatal sepsis. Splenocytes as well as purified T cells were prepared and then proliferative response and IL-2 productive capacities were measured. A significant suppression of splenocyte proliferation and IL-2 production was noticed in both sterile and septic animals compared to the T cells from unoperated control rats. In contrast, the proliferation and IL-2 production by nylon wool purified T cells in sterile rats was not significantly different from control rats, whereas, a significant suppression in Con A-mediated T-cell proliferation and IL-2 production noticed in septic rat T cells compared to the sterile and control rat T cells. Such decrease in T-cell proliferation and IL-2 production was accompanied with 20-25% deaths in neonates implanted with septic pellets. No mortality was noted in sterile-implanted neonates. Treatment of animals with COX-1 inhibitor had no effect on T-cell proliferation response in both septic and sterile groups, whereas COX-2 inhibitor abrogated the decrease in T-cell proliferative response in the septic group. The treatment

[Prader-Willi syndrome case with proliferative diabetic retinopathy in both eyes treated by early vitrectomy under local anesthesia].

Science.gov (United States)

Hori, Hideyuki; Sato, Yukihiro; Nakashima, Motohiro; Nakajima, Motohiro

2012-02-01

Although patients with Prader-Willi syndrome have a high rate of diabetes, to date, there have been only 4 reported cases (6 eyes) undergoing vitrectomy for proliferative diabetic retinopathy. Herein, we report a case of Prader-Willi syndrome with proliferative diabetic retinopathy that was treated by early vitrectomy OU under local anesthesia. A 30-year-old man was diagnosed as having Prader-Willi syndrome at the age of 2 years and diabetes at age 17. He was referred to our hospital as diabetic retinopathy had been detected in his first ophthalmological examination at age 29. Visual acuity was 0.6 bilaterally. Proliferative retinopathy, with cataract and macular edema, was identified in both eyes. Panretinal photocoagulation was performed on both eyes. However, proliferative membranes developed bilaterally, and vitreous hemorrhage occurred OS. Visual acuity decreased to 0.3 OU. The patient was hospitalized at our internal medicine department for blood glucose control. Subsequently, with an anesthesiologist on standby, a hypnotic sedative was injected intramuscularly, achieving retro-bulbar anesthesia. Combined cataract and vitreous surgery was performed on the left eye. One week later, a similar operation was performed on the right eye. The patient was discharged four days later. In the two years since these operation, visual acuity has been maintained at 0.8 OU. Patients with Prader-Willi syndrome should be examined for early detection and treatment of diabetic retinopathy.

Chronic proliferative synovitis of the equine metacarpophalangeal joint

International Nuclear Information System (INIS)

Kannegieter, N.J.

1990-01-01

Chronic proliferative synovitis of 27 metacarpophalangeal joints in 16 horses is described. The diagnosis was based on a history of lameness and, or, poor performance, pain on flexion of the metacarpophalangeal joint, the response to intra-articular anaesthesia, and plain and contrast radiography. Radiographic findings included concavity of the distal dorsal metacarpus proximal to the sagittal ridge, and an increase in size of the synovial tissue adjacent to the proximal, dorsal attachment of the joint capsule. Mineralisation of the synovial tissue was present in some joints, and chip fractures from the dorsal aspect of the proximal phalanx were also occasionally seen. Treatment by arthroscopic resection of the tissue gave excellent results

Erythrocyte fatty acids and risk of proliferative and nonproliferative fibrocystic disease in women in Shanghai, China.

Science.gov (United States)

Shannon, Jackilen; King, Irena B; Lampe, Johanna W; Gao, Dao Li; Ray, Roberta M; Lin, Ming-Gang; Stalsberg, Helge; Thomas, David B

2009-01-01

Although benign breast changes are more common than breast cancer, little evidence regarding risk factors for benign breast conditions is available. Omega-3 (n-3) fatty acids have antiinflammatory and antiproliferative actions and may be important in reducing the risk of benign conditions. There is a lack of research on the association of n-3 fatty acids with risk of benign fibrocystic breast changes. The objectives of the study were to evaluate the role of n-3 and other fatty acids in the development of benign proliferative fibrocystic conditions (PFCs) and nonproliferative fibrocystic conditions (NPFCs) in the breast and to evaluate the progression of fibrocystic changes in breast cancer. We conducted a case-control study to determine erythrocyte fatty acid concentrations in 155 women with NPFCs, 185 women with PFCs, 241 women with breast cancer (127 with nonproliferative and 114 with proliferative changes in the noncancerous extratumoral mammary epithelium), and 1,030 control subjects. We estimated the relative risk of NPFCs, PFCs, and breast cancer with proliferative and nonproliferative changes in extratumoral tissue compared with the risk of these changes alone. Women in the highest quartile of eicosapentaenoic acid concentrations were 67% less likely to have an NPFC alone or with breast cancer and 49% less likely to have breast cancer than were women with PFCs. gamma-Linolenic acid (18:3n-6) was positively associated with all fibrocystic and cancerous conditions. Palmitic:palmitoleic acid (n-7 saturation index) was inversely associated with risk in all comparisons. Our results support a protective effects of n-3 fatty acid intake and the n-7 saturation index against benign fibrocystic breast changes and the progression of proliferative changes to breast cancer.

Overview of the mutation spectrum in familial exudative vitreoretinopathy and Norrie disease with identification of 21 novel variants in FZD4, LRP5, and NDP.

Science.gov (United States)

Nikopoulos, Konstantinos; Venselaar, Hanka; Collin, Rob W J; Riveiro-Alvarez, Rosa; Boonstra, F Nienke; Hooymans, Johanna M M; Mukhopadhyay, Arijit; Shears, Deborah; van Bers, Marleen; de Wijs, Ilse J; van Essen, Anthonie J; Sijmons, Rolf H; Tilanus, Mauk A D; van Nouhuys, C Erik; Ayuso, Carmen; Hoefsloot, Lies H; Cremers, Frans P M

2010-06-01

Wnt signaling is a crucial component of the cell machinery orchestrating a series of physiological processes such as cell survival, proliferation, and migration. Among the plethora of roles that Wnt signaling plays, its canonical branch regulates eye organogenesis and angiogenesis. Mutations in the genes encoding the low density lipoprotein receptor protein 5 (LRP5) and frizzled 4 (FZD4), acting as coreceptors for Wnt ligands, cause familial exudative vitreoretinopathy (FEVR). Moreover, mutations in the gene encoding NDP, a ligand for these Wnt receptors, cause Norrie disease and FEVR. Both FEVR and Norrie disease share similar phenotypic characteristics, including abnormal vascularization of the peripheral retina and formation of fibrovascular masses in the eye that can lead to blindness. In this mutation update, we report 21 novel variants for FZD4, LRP5, and NDP, and discuss the putative functional consequences of missense mutations. In addition, we provide a comprehensive overview of all previously published variants in the aforementioned genes and summarize the phenotypic characteristics in mouse models carrying mutations in the orthologous genes. The increasing molecular understanding of Wnt signaling, related to ocular development and blood supply, offers more tools for accurate disease diagnosis that may be important in the development of therapeutic interventions.

Phenolic composition, antioxidant and anti-proliferative activities of edible and medicinal plants from the Peruvian Amazon

Directory of Open Access Journals (Sweden)

Jan Tauchen

Full Text Available ABSTRACT Among 23 extracts of medicinal and edible plants tested, Mauritia flexuosa L.f., Arecaceae, showed significant antioxidant ability (DPPH and ORAC = 1062.9 and 645.9 ± 51.4 µg TE/mg extract, respectively, while Annona montana Macfad., Annonaceae, demonstrated the most promising anti-proliferative effect (IC50 for Hep-G2 and HT-29 = 2.7 and 9.0 µg/ml, respectively. However, combinatory antioxidant/anti-proliferative effect was only detected in Oenocarpus bataua Mart., Arecaceae (DPPH = 903.8 and ORAC = 1024 µg TE/mg extract; IC50 for Hep-G2 and HT-29 at 102.6 and 38.8 µg/ml, respectively and Inga edulis Mart., Fabaceae (DPPH = 337.0 and ORAC = 795.7 µg TE/mg extract; IC50 for Hep-G2 and HT-29 at 36.3 and 57.9 µg/ml, respectively. Phenolic content was positively correlated with antioxidant potential, however not with anti-proliferative effect. None of these extracts possessed toxicity towards normal foetal lung cells, suggesting their possible use in development of novel plant-based agents with preventive and/or therapeutic action against oxidative stress-related diseases.

Long-term nonprogression and broad HIV-1-specific proliferative T-cell responses

Directory of Open Access Journals (Sweden)

Nesrina eImami

2013-03-01

Full Text Available Complex mechanisms underlying the maintenance of fully functional, proliferative, HIV-1-specific T-cell responses involve processes from early T-cell development through to the final stages of T-cell differentiation and antigen recognition. Virus-specific proliferative CD4 and CD8 T-cell responses, important for the control of infection, are observed in some HIV-1+ patients during early stages of disease, and are maintained in long-term nonprogressing subjects. In the vast majority of HIV-1+ patients, full immune functionality is lost when proliferative HIV-1-specific T-cell responses undergo a variable progressive decline throughout the course of chronic infection. This appears irreparable despite administration of potent combination antiretroviral therapy, which to date is non-curative, necessitating life-long administration and the development of effective, novel, therapeutic interventions. While a sterilising cure, involving clearance of virus from the host, remains a primary aim, a functional cure may be a more feasible goal with considerable impact on worldwide HIV-1 infection. Such an approach would enable long-term co-existence of host and virus in the absence of toxic and costly drugs. Effective immune homeostasis coupled with a balanced response appropriately targeting conserved viral antigens, in a manner that avoids hyperactivation and exhaustion, may prove to be the strongest correlate of durable viral control. This review describes novel concepts underlying full immune functionality in the context of HIV-1 infection, which may be utilised in future strategies designed to improve upon existing therapy. The aim will be to induce long-term nonprogressor or elite controller status in every infected host, through immune-mediated control of viraemia and reduction of viral reservoirs, leading to lower HIV-1 transmission rates.

Angiotensin-converting enzyme insertion/deletion gene polymorphism in Egyptian children with systemic lupus erythematosus: a possible relation to proliferative nephritis.

Science.gov (United States)

Hammad, A; Yahia, S; Laimon, W; Hamed, S M; Shouma, A; Shalaby, N M; Abdel-Hady, D; Ghanem, R; El-Farahaty, R M; El-Bassiony, S R; Hammad, E M

2017-06-01

Introduction Angiotensin-converting enzyme (ACE) is crucial in the pathogenesis of systemic lupus erythematosus through angiotensin II which regulates vascular tone and endothelial functions. Objectives To study the frequency of ACE insertion/deletion (I/D) gene polymorphism in Egyptian children with systemic lupus erythematosus and its possible relation to the renal pathology in cases with lupus nephritis. Subjects and methods The frequency of ACE gene insertion/deletion polymorphism genotypes was determined in 78 Egyptian children with systemic lupus erythematosus and compared to a matched group of 140 healthy controls using polymerase chain reaction. Results The DD genotype of the ACE gene was higher in systemic lupus erythematosus patients when compared to controls ( Plupus erythematosus patients in comparison to controls ( P lupus nephritis group, the DD genotype was significantly higher in those with proliferative lupus nephritis when compared to those with non-proliferative lupus nephritis ( P = 0.02; OR = 1.45; 95% CI = 1.4-1.6). Also, patients with proliferative lupus nephritis showed a higher frequency of the D allele ( P lupus erythematosus and occurrence of proliferative nephritis in Egyptian children.

Oral proliferative verrucous leukoplakia: A case report with an update

Directory of Open Access Journals (Sweden)

Rakhi Issrani

2013-01-01

Full Text Available White lesions both physiologic as well as pathologic are relatively frequent in the oral cavity, the most common pathology being oral leukoplakia (OL. There are many variants of OL, one of which is oral proliferative verrucous leukoplakia (OPVL. OPVL is a rare clinico-pathological entity, which is slow growing, long-term progressive lesion, but remains an enigmatic and difficult to define. The etiology of OPVL remains still unclear. Tobacco use does not seem to have a significant influence on the appearance of OPVL. These lesions may occur both in smokers and non-smokers. It is observed more frequently in women and elderly patients over 60 years at the time of diagnosis. The buccal mucosa and tongue are the most frequently involved sites. It develops initially as a white plaque of hyperkeratosis that eventually becomes a multifocal disease with confluent, exophytic and proliferative features. Various published case series have presented OPVL as a disease with aggressive biological behavior due to its high probability of recurrence and a high rate of malignant transformation. Prognosis is poor for this seemingly harmless-appearing white lesion of the oral mucosa. This article describes the clinical aspects and histologic features of an OPVL case that demonstrated the typical behavior pattern in a long-standing, persistent lesion and discusses this relatively rare entity in light of current information.

Elevated post-void residual volume in a geriatric post-hip fracture assessment in women-associated factors and risk of mortality.

Science.gov (United States)

Nuotio, Maria S; Luukkaala, Tiina; Tammela, Teuvo

2018-04-09

Multiple factors contribute to elevated post-void residual urine volumes (PVR), but they may indicate detrusor underactivity (DU), especially in older women. The aim here was to examine factors associated with and prognostic significance of elevated PVR in a geriatric post-hip fracture assessment in a female population. Consecutive female hip fracture patients (n = 409) aged 65 years and older were included. PVR was measured by bladder scanner. PVR of 160 ml or more was deemed elevated. Age-adjusted univariate logistic regression analyses were conducted to examine the association of the domains of the comprehensive geriatric assessment (CGA) with elevated PVR. Cox proportional hazards model was used to determine the age-adjusted association of an elevated PVR with 1-year mortality. Of the patients, 64 (15.6%) had elevated PVR. Having urinary or fecal incontinence, difficulties in physical activities of daily living, malnutrition, poor performance on Timed Up and Go and Elderly Mobility Scale were significantly associated with elevated PVR. Difficulties in instrumental activities of daily living, renal dysfunction, constipation, polypharmacy, nocturia, cognitive impairment and depressive mood were not associated with elevated PVR. Elevated PVR significantly increased the risk of mortality 1 year post hip fracture. Elevated PVR is relatively common in older female hip fracture patients and associated with physical functioning, malnutrition and risk of mortality. Even though a causal relationship cannot be confirmed, the findings may suggest a relationship between DU and physical frailty. PVR deserves to be included in the CGA of frail older patients including women.

Mass Spectrometry Imaging Can Distinguish on a Proteomic Level Between Proliferative Nodules Within a Benign Congenital Nevus and Malignant Melanoma.

Science.gov (United States)

Lazova, Rossitza; Yang, Zhe; El Habr, Constantin; Lim, Young; Choate, Keith Adam; Seeley, Erin H; Caprioli, Richard M; Yangqun, Li

2017-09-01

Histopathological interpretation of proliferative nodules occurring in association with congenital melanocytic nevi can be very challenging due to their similarities with congenital malignant melanoma and malignant melanoma arising in association with congenital nevi. We hereby report a diagnostically challenging case of congenital melanocytic nevus with proliferative nodules and ulcerations, which was originally misdiagnosed as congenital malignant melanoma. Subsequent histopathological examination in consultation by one of the authors (R.L.) and mass spectrometry imaging analysis rendered a diagnosis of congenital melanocytic nevus with proliferative nodules. In this case, mass spectrometry imaging, a novel method capable of distinguishing benign from malignant melanocytic lesions on a proteomic level, was instrumental in making the diagnosis of a benign nevus. We emphasize the importance of this method as an ancillary tool in the diagnosis of difficult melanocytic lesions.

Proliferative changes in nonpalpable breast lesions detected by mammography; Alteraciones profiferativas de la mama en lesiones no palpables detectadas por mamografia

Energy Technology Data Exchange (ETDEWEB)

Vega, A.; Delgado, A.; Ortega, E.; Garijo, F. [Hospital Universitario Marques de Valdecilla. Santander (Spain); Mosquera, J.; Sogo, C.; Alvarez, A. [Complejo Hospitalario Juan Canalejo. La Coruna (Spain)

2000-07-01

To analyze retrospectively the radiological findings in nonpalpable breast lesions detected by mammography that lead to the performance of surgical biopsy, resulting in a histological diagnosis of proliferative breast disease with and without atypia. From two Spanish hospitals, 421 women with 429 biopsies indicative of the presence of proliferative breast disease with and without atypia were selected out of a total of 1252 surgical biopsies in nonpalpable lesions that proved to be benign. Age, personal and familial history of breast cancer, reason for requesting the mammography and radiological findings that had indicated the need for surgical biopsy were recorded for each patient. The diagnosis was proliferative breast disease (epithelial hyperplasia) in 347 women with 354 biopsies and atypical hyperplasia in the remaining 74 women with 75 biopsies, representing 28% and 6%, respectively, of the 1252 biopsies of lesions found to be benign. In 221 of the 354 cases of epithelial hyperplasia (62%) and 45 of the 75 cases of atypical hyperplasia (60%), the presence of calcifications was the most common radiological findings leading to biopsy (p<0.05). Parenchymal distortion, with or without calcifications, was the second most common radiological sign. The histological study revealed a close relationship between these proliferative events and radial scars. Calcifications are the radiological finding that most frequently indicate the need for surgical biopsy in nonpalpable lesions that results in a diagnosis of proliferative breast disease with and without atypia. (Author) 12 refs.

Anti-Myeloperoxidase Antibodies Associate with Future Proliferative Lupus Nephritis

Directory of Open Access Journals (Sweden)

S. W. Olson

2017-01-01

Full Text Available Background. The subclinical pathophysiology of proliferative lupus nephritis (PLN has not been fully elucidated. Myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA is associated with PLN, but prediagnostic levels have not been reported. Methods. We performed a retrospective case-control Department of Defense Serum Repository (DoDSR study comparing MPO-ANCA levels in longitudinal prediagnostic serum samples for 23 biopsy confirmed proliferative lupus nephritis (PLN patients to DoDSR identified age, sex, race, and age of serum matched healthy and SLE without LN disease controls. We also compared the temporal relationship of MPO-ANCA to anti-double stranded DNA antibodies (dsDNAab. Results. A greater proportion of PLN patients had prediagnostic MPO-ANCA levels above ≥3 U/mL and ≥6 U/mL compared to SLE without LN (91% versus 43%, p<0.001; 57% versus 5%, p<0.001, resp.. In subgroup analysis, the MPO-ANCA threshold of ≥3 U/mL was significant at <1 year (88% versus 39%, p=0.007 and 1–4 years (87% versus 38%, p=0.009 prior to diagnosis. Statistically significant subclinical MPO-ANCA levels (≥3 U/mL occurred prior to statistically significant dsDNAab ≥ 3 IU/ml (89% versus 11%, p=0.003. Conclusions. Subclinical MPO-ANCA levels could distinguish future PLN from SLE without LN. MPO-ANCA manifests prior to clinical disease and subclinical dsDNAab to suggest that it may contribute directly to PLN pathogenicity.

Vitrectomy for proliferative diabetic retinopathy

Directory of Open Access Journals (Sweden)

Chao Peng

2013-10-01

Full Text Available AIM:To observe the clinical effect of vitrectomy for proliferative diabetic retinopathy(PDR.METHODS: The clinical data of 55 cases(65 eyes, underwent vitrectomy, membrane peeling, endolaser photocoagulation and silicone oil or C3F8 injection, were retrospectively studied. During 6 months to 1 year follow-up period, visual acuity, intraocular pressure, retinal conditions and complications were observed.RESULTS: All 65 eyes received vitrectomy, of which silicone oil was tamponaded in 32 eyes, C3F8 was injected in 8 eyes, BBS was filled in 25 eyes. Visual improvement achieved in 42 eyes. Two eyes were manually vision, form count fingers to 0.05 in 18 eyes, >0.05-0.1 in 28 eyes, >0.1-0.3 in 12 eyes and >0.3 in 5 eyes. Retinal hole was occurred in 7 eyes, limitations fibrosis membrane remained in 8 eyes, retinal detachment appeared in 5 eyes, IOP increased in 18 eyes, vitreous hemorrhage relapsed in 12 eyes, 36 eyes received supplemental photocoagulation treatment 1-3 times after operation.CONCLUSION:Vitrectomy combined endophotocoagulation is an effective treatment for PDR. Silicone oil tamponade can limit the hemorrhage.

Epithelial ingrowth under a laser in situ keratomileusis flap after phacoemulsification.

Science.gov (United States)

Braunstein, Richard E; Airiani, Suzanna; Chang, Stanley

2003-11-01

A 47-year-old man was referred to us for management of a cataract in the left eye. The patient had an ocular history of high myopia with anisometropia, amblyopia in the left eye, and stable myopic lattice degeneration in both eyes. The patient had successful bilateral laser in situ keratomileusis 3 years before and multiple retinal surgeries for treatment of a rhegmatogenous retinal detachment associated with a giant retinal tear in the temporal region of the retina with subsequent proliferative vitreoretinopathy. Phacoemulsification was performed uneventfully. A single interrupted 10-0 nylon suture was placed in the temporal clear corneal wound and removed 7 weeks postoperatively. One month later, slitlamp examination revealed a 1.5 mm tongue-like area of epithelial ingrowth under the corneal flap. The epithelial cells seemed to enter the flap-stroma interface through the previously placed suture tract and advanced centrally.

Triterpenoid Saponins from Anemone rivularis var. Flore-Minore and Their Anti-Proliferative Activity on HSC-T6 Cells.

Science.gov (United States)

Wang, Xiao-Yang; Gao, Hui; Xie, Xiao-Jie; Jurhiin, Jirimubatu; Zhang, Mu-Zi-He; Zhou, Yan-Ping; Liu, Rui; Ning, Meng; Han, Jin; Tang, Hai-Feng

2018-02-23

Five previously undescribed triterpenoid saponins ( 1 - 5 ), along with eight known ones ( 6 - 13 ), were isolated from the whole plants of Anemone rivularis var. flore-minore . Their structures were clarified by extensive spectroscopic data and chemical evidence. For the first time, the lupane-type saponins ( 3 and 12 ) were reported from the Anemone genus. The anti-proliferative activity of all isolated saponins was evaluated on hepatic stellate cells (HSC-T6). Saponins 12 and 13 , which possess more monosaccharides than the others, displayed potent anti-proliferative activity, with IC 50 values of 18.21 and 15.56 μM, respectively.

Erythrocyte fatty acids and risk of proliferative and nonproliferative fibrocystic disease in women in Shanghai, China123

Science.gov (United States)

Shannon, Jackilen; King, Irena B; Lampe, Johanna W; Gao, Dao Li; Ray, Roberta M; Lin, Ming-Gang; Stalsberg, Helge; Thomas, David B

2009-01-01

Background: Although benign breast changes are more common than breast cancer, little evidence regarding risk factors for benign breast conditions is available. Omega-3 (n–3) fatty acids have antiinflammatory and antiproliferative actions and may be important in reducing the risk of benign conditions. There is a lack of research on the association of n–3 fatty acids with risk of benign fibrocystic breast changes. Objectives: The objectives of the study were to evaluate the role of n–3 and other fatty acids in the development of benign proliferative fibrocystic conditions (PFCs) and nonproliferative fibrocystic conditions (NPFCs) in the breast and to evaluate the progression of fibrocystic changes in breast cancer. Design: We conducted a case-control study to determine erythrocyte fatty acid concentrations in 155 women with NPFCs, 185 women with PFCs, 241 women with breast cancer (127 with nonproliferative and 114 with proliferative changes in the noncancerous extratumoral mammary epithelium), and 1030 control subjects. We estimated the relative risk of NPFCs, PFCs, and breast cancer with proliferative and nonproliferative changes in extratumoral tissue compared with the risk of these changes alone. Results: Women in the highest quartile of eicosapentaenoic acid concentrations were 67% less likely to have an NPFC alone or with breast cancer and 49% less likely to have breast cancer than were women with PFCs. γ-Linolenic acid (18:3n–6) was positively associated with all fibrocystic and cancerous conditions. Palmitic:palmitoleic acid (n–7 saturation index) was inversely associated with risk in all comparisons. Conclusion: Our results support a protective effects of n–3 fatty acid intake and the n–7 saturation index against benign fibrocystic breast changes and the progression of proliferative changes to breast cancer. PMID:19056601

Elevated postvoid residual urine volume predicting recurrence of urinary tract infections in toilet-trained children.

Science.gov (United States)

Chang, Shang-Jen; Tsai, Li-Ping; Hsu, Chun-Kai; Yang, Stephen S

2015-07-01

The aim of this study was to examine whether toilet-trained children with a history of febrile urinary tract infection (fUTI) and elevated postvoid residual (PVR) urine volume according to a recently published PVR nomogram were at greater risk of UTI recurrence. One month after recovery from febrile UTI, constipation was diagnosed according to the Rome III criteria, and lower urinary tract (LUT) function was evaluated with two sets of uroflowmetry and PVR by ultrasonography. For children aged ≦ 6 and ≧ 7 years, elevated PVR is defined as >20 and >10 ml, respectively. Cox proportion hazards regression was used to evaluate the risk factors for recurrence of UTI. Between 2005 and 2011, 60 children aged 6.5 ± 2.5 years (boy:girl ratio 27:33) were enrolled for analysis. Univariate analysis showed that recurrent febrile UTI was more commonly observed in children with elevated PVR [repetitive elevated PVR: hazard ratio (HR) 5.75, 95% confidence interval (CI) 1.41-23.4; one elevated PVR: HR 4.53, 95% CI 1.01-20.2] and high-grade vesicoureteral reflux (VUR; HR 4.53, 95% CI 1.46-14.07). Multivariate analysis showed that younger age (HR 1.37, 95% CI 1.03-1.82, p UTI--but not gender, presence of high-grade VUR and constipation. Elevated PVR defined by the new PVR nomogram predicted recurrent UTI in children with history of febrile UTI. Care should be taken to manage children with elevated PVR.

Epithelial cell proliferative activity of Barrett's esophagus : methodology and correlation with traditional cancer risk markers

NARCIS (Netherlands)

Peters, FTM; Ganesh, S; Kuipers, EJ; De Jager-Krikken, A; Karrenbeld, A; Harms, Geert; Sluiter, WJ; Koudstaal, J; Klinkenberg-Knol, EC; Lamers, CBHW; Kleibeuker, JH

Barrett's esophagus (BE) is a premalignant condition, due to chronic gastroesophageal reflux. Effective antireflux therapy may diminish cancer risk. To evaluate this option an intermediate marker is needed. We developed a methodology for measurement of epithelial cell proliferative activity of

cExternal beam radiation results in minimal changes in post void residual urine volumes during the treatment of clinically localized prostate cancer

International Nuclear Information System (INIS)

Orio, Peter F III; Merrick, Gregory S; Allen, Zachariah A; Butler, Wayne M; Wallner, Kent E; Kurko, Brian S; Galbreath, Robert W

2009-01-01

To evaluate the impact of external beam radiation therapy (XRT) on weekly ultrasound determined post-void residual (PVR) urine volumes in patients with prostate cancer. 125 patients received XRT for clinically localized prostate cancer. XRT was delivered to the prostate only (n = 66) or if the risk of lymph node involvement was greater than 10% to the whole pelvis followed by a prostate boost (n = 59). All patients were irradiated in the prone position in a custom hip-fix mobilization device with an empty bladder and rectum. PVR was obtained at baseline and weekly. Multiple clinical and treatment parameters were evaluated as predictors for weekly PVR changes. The mean patient age was 73.9 years with a mean pre-treatment prostate volume of 53.3 cc, a mean IPSS of 11.3 and a mean baseline PVR of 57.6 cc. During treatment, PVR decreased from baseline in both cohorts with the absolute difference within the limits of accuracy of the bladder scanner. Alpha-blockers did not predict for a lower PVR during treatment. There was no significant difference in mean PVR urine volumes or differences from baseline in either the prostate only or pelvic radiation groups (p = 0.664 and p = 0.458, respectively). Patients with a larger baseline PVR (>40 cc) had a greater reduction in PVR, although the greatest reduction was seen between weeks one and three. Patients with a small PVR (<40 cc) had no demonstrable change throughout treatment. Prostate XRT results in clinically insignificant changes in weekly PVR volumes, suggesting that radiation induced bladder irritation does not substantially influence bladder residual urine volumes

cExternal beam radiation results in minimal changes in post void residual urine volumes during the treatment of clinically localized prostate cancer

Directory of Open Access Journals (Sweden)

Wallner Kent E

2009-07-01

Full Text Available Abstract Background To evaluate the impact of external beam radiation therapy (XRT on weekly ultrasound determined post-void residual (PVR urine volumes in patients with prostate cancer. Methods 125 patients received XRT for clinically localized prostate cancer. XRT was delivered to the prostate only (n = 66 or if the risk of lymph node involvement was greater than 10% to the whole pelvis followed by a prostate boost (n = 59. All patients were irradiated in the prone position in a custom hip-fix mobilization device with an empty bladder and rectum. PVR was obtained at baseline and weekly. Multiple clinical and treatment parameters were evaluated as predictors for weekly PVR changes. Results The mean patient age was 73.9 years with a mean pre-treatment prostate volume of 53.3 cc, a mean IPSS of 11.3 and a mean baseline PVR of 57.6 cc. During treatment, PVR decreased from baseline in both cohorts with the absolute difference within the limits of accuracy of the bladder scanner. Alpha-blockers did not predict for a lower PVR during treatment. There was no significant difference in mean PVR urine volumes or differences from baseline in either the prostate only or pelvic radiation groups (p = 0.664 and p = 0.458, respectively. Patients with a larger baseline PVR (>40 cc had a greater reduction in PVR, although the greatest reduction was seen between weeks one and three. Patients with a small PVR ( Conclusion Prostate XRT results in clinically insignificant changes in weekly PVR volumes, suggesting that radiation induced bladder irritation does not substantially influence bladder residual urine volumes.

Proliferative retinopathy and proteinuria predict mortality rate in type 1 diabetic patients from Fyn County, Denmark

DEFF Research Database (Denmark)

Grauslund, J; Green, A; Sjølie, A K

2008-01-01

AIMS/HYPOTHESIS: We evaluated the effect of diabetic retinopathy on 25 year survival rate among a population-based cohort of type 1 diabetic patients from Fyn County, Denmark. METHODS: In 1973 all diabetic patients from Fyn County, Denmark with onset before the age of 30 years as of 1 July 1973...... were identified (n=727). In 1981, only 627 patients were still alive and resident in Denmark. Of these, 573 (91%) participated in a clinical baseline examination, in which diabetic retinopathy was graded and other markers of diabetes measured. Mortality rate was examined in a 25 year follow....../INTERPRETATION: Proliferative retinopathy and proteinuria predict mortality rate in a population-based cohort of type 1 diabetic patients. In combination they act even more strongly. Non-proliferative diabetic retinopathy did not affect survival rate....

Correlation of proliferative and clonogenic tumor cells in multiple myeloma

International Nuclear Information System (INIS)

Karp, J.E.; Burke, P.J.; Saylor, P.L.; Humphrey, R.L.

1984-01-01

To expand on the findings from previous clinical trials that the growth of residual tumor is increased at a predictable time following initial drug administration, malignant plasma cells from bone marrows of patients with multiple myeloma (MM) were examined for changes in proliferation and clonogenicity induced in vivo by cyclophosphamide and in vitro by drug-induced humoral stimulatory activity. Peak plasma cell [ 3 H]thymidine labeling index (LI) occurred predictably following drug and paralleled changes in agar colony formation by marrow cells obtained during therapy. Colony-forming capacity of pretreatment MM marrow populations was enhanced when those cells were cultured with humoral stimulatory activity, similar to the increased colony formation detected in Day 9 postcyclophosphamide marrows at the time of peak plasma cell LI. To further define a relationship between proliferative plasma cells and colony-forming tumor cells, MM marrows were fractionated by sedimentation on an isokinetic gradient. Enrichment of a proliferative tumor cell cohort was achieved, evidenced by [ 3 H]thymidine LI. Colony-forming cells were also enriched by isokinetic gradient sedimentation, and agar colony formation by MM marrow cell fractions correlated with the kinetic characteristics of the isolated subpopulations. These studies of whole and fractionated human MM marrow cell populations suggest that the kinetically active cells which are induced to proliferate in vivo and in vitro are closely related to the clonogenic tumor cells which produce colonies in agar and which, like those cells measured by [ 3 H]thymidine LI, respond to growth stimulation by drug-induced humoral stimulatory activity

Easy labeling of proliferative phase and sporogonic phase of microsporidia Nosema bombycis in host cells.

Directory of Open Access Journals (Sweden)

Jie Chen

Full Text Available Microsporidia are eukaryotic, unicellular parasites that have been studied for more than 150 years. These organisms are extraordinary in their ability to invade a wide range of hosts including vertebrates and invertebrates, such as human and commercially important animals. A lack of appropriate labeling methods has limited the research of the cell cycle and protein locations in intracellular stages. In this report, an easy fluorescent labeling method has been developed to mark the proliferative and sporogonic phases of microsporidia Nosema bombycis in host cells. Based on the presence of chitin, Calcofluor White M2R was used to label the sporogonic phase, while β-tubulin antibody coupled with fluorescence secondary antibody were used to label the proliferative phase by immunofluorescence. This method is simple, efficient and can be used on both infected cells and tissue slices, providing a great potential application in microsporidia research.

Cdc6 is a rate-limiting factor for proliferative capacity during HL60 cell differentiation

International Nuclear Information System (INIS)

Barkley, Laura R.; Hong, Hye Kyung; Kingsbury, Sarah R.; James, Michelle; Stoeber, Kai; Williams, Gareth H.

2007-01-01

The DNA replication (or origin) licensing pathway represents a critical step in cell proliferation control downstream of growth signalling pathways. Repression of origin licensing through down-regulation of the MCM licensing factors (Mcm2-7) is emerging as a ubiquitous route for lowering proliferative capacity as metazoan cells exit the cell division cycle into quiescent, terminally differentiated and senescent 'out-of-cycle' states. Using the HL60 monocyte/macrophage differentiation model system and a cell-free DNA replication assay, we have undertaken direct biochemical investigations of the coupling of origin licensing to the differentiation process. Our data show that down-regulation of the MCM loading factor Cdc6 acts as a molecular switch that triggers loss of proliferative capacity during early engagement of the somatic differentiation programme. Consequently, addition of recombinant Cdc6 protein to in vitro replication reactions restores DNA replication competence in nuclei prepared from differentiating cells. Differentiating HL60 cells over-expressing either wild-type Cdc6 or a CDK phosphorylation-resistant Cdc6 mutant protein (Cdc6A4) exhibit an extended period of cell proliferation compared to mock-infected cells. Notably, differentiating HL60 cells over-expressing the Cdc6A4 mutant fail to down-regulate Cdc6 protein levels, suggesting that CDK phosphorylation of Cdc6 is linked to its down-regulation during differentiation and the concomitant decrease in cell proliferation. In this experimental model, Cdc6 therefore plays a key role in the sequential molecular events leading to repression of origin licensing and loss of proliferative capacity during execution of the differentiation programme

Curative-intent Surgery for Perihilar Cholangiocarcinoma with and without Portal Vein Resection - A Comparative Analysis of Early and Late Outcomes.

Science.gov (United States)

Dumitraşcu, Traian; Stroescu, Cezar; Braşoveanu, Vladislav; Herlea, Vlad; Ionescu, Mihnea; Popescu, Irinel

2017-01-01

Introduction: The safety of portal vein resection (PVR) during surgery for perihilar cholangiocarcinoma (PHC) has been demonstrated in Asia, America, and Western Europe. However, no data about this topic are reported from Eastern Europe. The aim of the present study is to comparatively assess the early and long-term outcomes after resection for PHC with and without PVR. The data of 21 patients with PVR were compared with those of 102 patients with a curative-intent surgery for PHC without PVR. The appropriate statistical tests were used to compare different variables between the groups. Results: A PVR was performed in 17% of the patients. In the PVR group, significantly more right trisectionectomies (p=0.031) and caudate lobectomies (0.049) were performed and, as expected, both the operative time (p=0.015) and blood loss (p=0.002) were significantly higher. No differences between the groups were observed regarding the severe postoperative morbidity and mortality rates, and completion of adjuvant therapy. However, in the PVR group the postoperative clinicallyrelevant liver failure rate was significantly higher (p=0.001). No differences between the groups were observed for the median overall survival times (34 vs. 26 months, p = 0.566). A histological proof of the venous tumor invasion was observed in 52% of the patients with a PVR and was associated with significantly worse survival (p=0.027). A PVR can be safely performed during resection for PHC, without significant added severe morbidity or mortality rates. However, clinically-relevant liver failure rates are significantly higher when a PVR is performed. Furthermore, increased operative times and blood loss should be expected when a PVR is performed. Histological tumor invasion of the portal vein is associated with significantly worse survival. Celsius.

Is valve choice a significant determinant of paravalular leak post-transcatheter aortic valve implantation? A systematic review and meta-analysis.

Science.gov (United States)

O'Sullivan, Katie E; Gough, Aideen; Segurado, Ricardo; Barry, Mitchel; Sugrue, Declan; Hurley, John

2014-05-01

Paravalvular regurgitation (PVR) following transcatheter aortic valve implantation (TAVI) is associated with poor survival. The two main valve delivery systems used to date differ significantly in both structure and deployment technique. The primary objective of this study was to perform a systematic review and meta-analysis of studies identifying PVR in patients post-TAVI using Medtronic CoreValve (MCV) and Edward Sapien (ES) valves in order to identify whether a significant difference exists between valve types. The secondary objective was to identify additional factors predisposing to PVR to provide an overview of the other associated considerations. A systematic review and meta-analysis of the current literature to identify PVR rate in patients with MCV and ES valves was performed. We also sought to examine other factors predisposing to PVR. A total of 5910 patients were identified from 9 studies. PVR rates for MCV and ES were analysed. MCV was associated with a higher PVR rate of 15.75% [95% confidence interval (CI) 12.48-19.32] compared with ES 3.93% [95% CI 1.05-8.38]. We separately reviewed predisposing factors associated with PVR. A formal comparison of the MCV and ES valve leakage rates by mixed-effects meta-regression with a fixed-effect moderator variable for valve type (MCV or ES) suggested a statistically significant difference in leakage rate between the two valve types (P = 0.0002). Unfavourable anatomical and pathological factors as well as valve choice have an impact on rates of PVR. Additionally, certain anatomical features dictate valve choice. A direct comparison of all the predisposing factors at this time is not possible and will require prospective multivariate analysis. There is, however, a significant difference in the PVR rates between valves based on the published observational data available to date. The ES valve associated with a lower incidence of PVR overall; therefore, we conclude that valve choice is indeed a significant

In vitro anti-proliferative and anti-inflammatory activity of leaf and fruit extracts from Vaccinium bracteatum Thunb.

Science.gov (United States)

Landa, Premysl; Skalova, Lenka; Bousova, Iva; Kutil, Zsofia; Langhansova, Lenka; Lou, Ji-Dong; Vanek, Tomas

2014-01-01

The aim of this study was to evaluate in vitro anti-proliferative (tested on MCF-7, MDA-MB-231, and MCF-10A cell lines) and anti-inflammatory (evaluated as inhibition of prostaglandin E2 synthesis catalyzed by cyclooxygenase-2) effect of various extracts from Vaccinium bracteatum leaves and fruits. The highest anti-proliferative effect possessed leaf dichloromethane extract with IC50 values ranging from 93 to 198 μg/mL. In the case of cyclooxygenase-2 inhibition, n-hexane, dichloromethane, and ethanol fruit extracts showed the best activity with IC50 values = 2.0, 5.4, and 12.7 μg/mL, respectively. These results indicate that V. bracteatum leaves and fruits could be useful source of anti-cancer and anti-inflammatory compounds.

In vitro anti-proliferative activity on colon cancer cell line (HT-29) of Thai medicinal plants selected from Thai/Lanna medicinal plant recipe database "MANOSROI III".

Science.gov (United States)

Manosroi, Aranya; Akazawa, Hiroyuki; Akihisa, Toshihiro; Jantrawut, Pensak; Kitdamrongtham, Worapong; Manosroi, Worapaka; Manosroi, Jiradej

2015-02-23

Thai/Lanna region has its own folklore wisdoms including the traditional medicinal plant recipes. Thai/Lanna medicinal plant recipe database "MANOSROI III" has been developed by Prof. Dr. Jiradej Manosroi. It consists of over 200,000 recipes for all diseases including cancer. To investigate the anti-proliferative and apoptotic activities on human colon cancer cell line (HT-29) as well as the cancer cell selectivity of the methanolic extracts (MEs) and fractions of the 23 selected plants from the "MANOSROI III" database. The 23 selected plants were extracted with methanol under reflux and evaluated for their anti-proliferative activity by sulforhodamine B assay. The 5 plants (Gloriosa superba, Caesalpinia sappan, Fibraurea tinctoria, Ventilago denticulata and Psophocarpus tetragonolobus) with potent anti-proliferative activity were fractionated by liquid-liquid partition to give 4 fractions including each hexane (HF), methanol-water (MF), n-butanol (BF) and water (WF) fractions. They were tested for anti-proliferative activity and cancer cell selectivity. The ME and fractions of G. superba which showed potent anti-proliferative activity were further examined for morphological changes and apoptotic activities by acridine orange (AO)/ethidium bromide (EB) staining. The ME of G. superba root showed active with the highest anti-proliferative activity at 9.17 and 1.58 folds of cisplatin and doxorubicin, respectively. After liquid-liquid partition, HF of V. denticulata, MFs of F. tinctoria, V. denticulata and BF of P. tetragonolobus showed higher anti-proliferative activities than their MEs. The MF of G. superba indicated the highest anti-proliferative activity at 7.73 and 1.34 folds of cisplatin and doxorubicin, respectively, but only 0.86 fold of its ME. The ME and HF, MF and BF of G. superba and MF of F. tinctoria demonstrated high cancer cell selectivity. At 50 µg/ml, ME, HF, MF and BF of G. superba demonstrated higher apoptotic activities than the two standard drugs

Developmental control of transcriptional and proliferative potency during the evolutionary emergence of animals

Science.gov (United States)

Arenas-Mena, Cesar; Coffman, James A.

2016-01-01

Summary It is proposed that the evolution of complex animals required repressive genetic mechanisms for controlling the transcriptional and proliferative potency of cells. Unicellular organisms are transcriptionally potent, able to express their full genetic complement as the need arises through their life cycle, whereas differentiated cells of multicellular organisms can only express a fraction of their genomic potential. Likewise, whereas cell proliferation in unicellular organisms is primarily limited by nutrient availability, cell proliferation in multicellular organisms is developmentally regulated. Repressive genetic controls limiting the potency of cells at the end of ontogeny would have stabilized the gene expression states of differentiated cells and prevented disruptive proliferation, allowing the emergence of diverse cell types and functional shapes. We propose that distal cis-regulatory elements represent the primary innovations that set the stage for the evolution of developmental gene regulatory networks and the repressive control of key multipotency and cell-cycle control genes. The testable prediction of this model is that the genomes of extant animals, unlike those of our unicellular relatives, encode gene regulatory circuits dedicated to the developmental control of transcriptional and proliferative potency. PMID:26173445

GTP depletion synergizes the anti-proliferative activity of chemotherapeutic agents in a cell type-dependent manner

International Nuclear Information System (INIS)

Lin, Tao; Meng, Lingjun; Tsai, Robert Y.L.

2011-01-01

Highlights: → Strong synergy between mycophenolic acid (MPA) and 5-FU in MDA-MB-231 cells. → Cell type-dependent synergy between MPA and anti-proliferative agents. → The synergy of MPA on 5-FU is recapitulated by RNA polymerase-I inhibition. → The synergy of MPA on 5-FU requires the expression of nucleostemin. -- Abstract: Mycophenolic acid (MPA) depletes intracellular GTP by blocking de novo guanine nucleotide synthesis. GTP is used ubiquitously for DNA/RNA synthesis and as a signaling molecule. Here, we made a surprising discovery that the anti-proliferative activity of MPA acts synergistically with specific chemotherapeutic agents in a cell type-dependent manner. In MDA-MB-231 cells, MPA shows an extremely potent synergy with 5-FU but not with doxorubicin or etoposide. The synergy between 5-FU and MPA works most effectively against the highly tumorigenic mammary tumor cells compared to the less tumorigenic ones, and does not work in the non-breast cancer cell types that we tested, with the exception of PC3 cells. On the contrary, MPA shows the highest synergy with paclitaxel but not with 5-FU in SCC-25 cells, derived from oral squamous cell carcinomas. Mechanistically, the synergistic effect of MPA on 5-FU in MDA-MB-231 cells can be recapitulated by inhibiting the RNA polymerase-I activity and requires the expression of nucleostemin. This work reveals that the synergy between MPA and anti-proliferative agents is determined by cell type-dependent factors.

Effect of postradiation bleeding on proliferative activity of cells in small intestine crypts of rats

Energy Technology Data Exchange (ETDEWEB)

Petrovic, N V [Institut za Nuklearne Nauke Boris Kidric, Vinca (Yugoslavia)

1975-12-01

The effect of postradiation bleeding on the dynamics of duodenal crypt's cell proliferation in rats was studied. The animals, females, three months old, weighing 170 or 180 g, were exposed to radiation of 800 R (115 R/min) and immediately after irradiation were bled by cardiac puncture to 50% of total blood volume. Proliferative activity of duodenal epithelium cells was monitored for a period of five days after irradiation. For control purposes normal, irradiated and only bled animals were used. The results demonstrated that although there are no significant differences in proliferative activity of duodenal epithelium cells in irradiated and bled animals and only irradiated animals, the postradiation reparative processes in irradiated and bled animals is considerably more stable. It is considered that bleeding itself by its hypoxic activity reduced the sensitivity of epithelium to the dose of radiation used. On the other hand, bleeding removed the damaging agents which appear after total body irradiation.

Panretinal photocoagulation versus intravitreal injection retreatment pain in high-risk proliferative diabetic retinopathy

Directory of Open Access Journals (Sweden)

Célia Regina Farias de Araújo Lucena

2013-02-01

Full Text Available PURPOSE: To compare pain related to intravitreal injection and panretinal photocoagulation in the management of patients with high-risk proliferative diabetic retinopathy. METHODS: Prospective study including patients with high-risk proliferative diabetic retinopathy and no prior laser treatment randomly assigned to receive panretinal photocoagulation (PRP group or panretinal photocoagulation plus intravitreal ranibizumab (PRPplus group. In all patients, panretinal photocoagulation was administered in two sessions (weeks 0 and 2, and intravitreal ranibizumab was administered at the end of the first laser session in the PRPplus group. Retreatment was performed at weeks 16 and 32 if active new vessels were detected at fluorescein angiography. Patients in the PRPplus group received intravitreal ranibizumab and patients in the PRP group received 500-µm additional spots per quadrant of active new vessels. After the end of retreatment, a 100-degree Visual Analog Scale was used for pain score estimation. The patient was asked about the intensity of pain during the whole procedure (retinal photocoagulation session or intravitreal ranibizumab injection. Statistics for pain score comparison were performed using a non-parametric test (Wilcoxon rank sums. RESULTS: Seventeen patients from PRPplus and 14 from PRP group were evaluated for pain scores. There were no significant differences between both groups regarding gender, glycosylated hemoglobin and disease duration. Mean intravitreal injection pain (±SEM was 4.7 ± 2.1 and was significantly lower (p<0.0001 than mean panretinal photocoagulation pain (60.8 ± 7.8. Twelve out of 17 patients from the PRPplus group referred intensity pain score of zero, while the minimal score found in PRP group was found in one patient with 10.5. CONCLUSION: In patients with high-risk proliferative diabetic retinopathy who needed retreatment for persistent new vessels, there was more comfort for the patient when retreatment

[Effect of internal limiting membrane peeling on morpho-functional state of the retina in patients with proliferative diabetic retinopathy (preliminary report)].

Science.gov (United States)

Bikbov, M M; Fayzrakhmanov, R R; Kalanov, M R

2018-01-01

To compare morpho-functional parameters of retina during vitrectomy with and without internal limiting membrane (ILM) peeling in patients with proliferative diabetic retinopathy. The study included 55 patients (55 eyes) that had underwent vitreoretinal surgery in the setting of antivasoproliferative therapy for proliferative diabetic retinopathy. Patients of the 1 st group (n=27) underwent vitrectomy with silicone tamponade, 2 nd group (n=28) received similar treatment with the addition of ILM peeling. Three months after the treatment, all patients had silicone oil removed. Best Corrected Visual Acuity before treatment was 0.06±0.02 in both groups; after the treatment it improved to 0.1±0.05 (ppeeling during vitrectomy with following silicone oil tamponade eliminates the risk of ERM formation in patients with proliferative diabetic retinopathy in the follow-up period of up to 6-month and results in better morpho-functional parameters in comparison with patients who received similar treatment but without peeling.

The proliferative human monocyte subpopulation contains osteoclast precursors

Science.gov (United States)

Lari, Roya; Kitchener, Peter D; Hamilton, John A

2009-01-01

Introduction Immediate precursors of bone-resorbing osteoclasts are cells of the monocyte/macrophage lineage. Particularly during clinical conditions showing bone loss, it would appear that osteoclast precursors are mobilized from bone marrow into the circulation prior to entering tissues undergoing such loss. The observed heterogeneity of peripheral blood monocytes has led to the notion that different monocyte subpopulations may have special or restricted functions, including as osteoclast precursors. Methods Human peripheral blood monocytes were sorted based upon their degree of proliferation and cultured in macrophage colony-stimulating factor (M-CSF or CSF-1) and receptor activator of nuclear factor-kappa-B ligand (RANKL). Results The monocyte subpopulation that is capable of proliferation gave rise to significantly more multinucleated, bone-resorbing osteoclasts than the bulk of the monocytes. Conclusions Human peripheral blood osteoclast precursors reside in the proliferative monocyte subpopulation. PMID:19222861

APPROACHES TO THE CONSTRUCTION OF THE VITRECTOMY RISK MANAGEMENT SYSTEM IN PATIENTS WITH PROLIFERATIVE DIABETIC RETINOPATHY

Directory of Open Access Journals (Sweden)

A. M. Ruban

2016-08-01

Full Text Available The article presents the some approaches to create a system support of making decision during vitrectomy in patients with diabetic proliferative retinopathy, promotes objective assessment of individual risk-management for patient and allows optimize ophthalmological care for them.

Inhibition of human lymphocyte proliferative response by serum from Plasmodium falciparum infected patients

DEFF Research Database (Denmark)

Theander, T G; Svenson, M; Bygbjerg, I C

1987-01-01

initiation of treatment suppressed the in vitro lymphocyte proliferative response to both Plasmodium-derived antigens and an unrelated antigen (PPD-tuberculin). The suppressive effect was lost if the serum was incubated at 56 degrees C for 30 min, and the effect was not HLA-restricted since the inhibition...

Polish natural bee honeys are anti-proliferative and anti-metastatic agents in human glioblastoma multiforme U87MG cell line.

Directory of Open Access Journals (Sweden)

Justyna Moskwa

Full Text Available Honey has been used as food and a traditional medicament since ancient times. However, recently many scientists have been concentrating on the anti-oxidant, anti-proliferative, anti-inflammatory and other properties of honey. In this study, we investigated for the first time an anticancer effect of different honeys from Poland on tumor cell line - glioblastoma multiforme U87MG. Anti-proliferative activity of honeys and its interferences with temozolomide were determined by a cytotoxicity test and DNA binding by [H3]-thymidine incorporation. A gelatin zymography was used to conduct an evaluation of metalloproteinases (MMP-2 and MMP-9 expression in U87MG treatment with honey samples. The honeys were previously tested qualitatively (diastase activity, total phenolic content, lead and cadmium content. The data demonstrated that the examined honeys have a potent anti-proliferative effect on U87MG cell line in a time- and dose-dependent manner, being effective at concentrations as low as 0.5% (multifloral light honey - viability 53% after 72 h of incubation. We observed that after 48 h, combining honey with temozolomide showed a significantly higher inhibitory effect than the samples of honey alone. We observed a strong inhibition of MMP-2 and MMP-9 for the tested honeys (from 20 to 56% and from 5 to 58% compared to control, respectively. Our results suggest that Polish honeys have an anti-proliferative and anti-metastatic effect on U87MG cell line. Therefore, natural bee honey can be considered as a promising adjuvant treatment for brain tumors.

Analysis of the proliferative potential of odontogenic epithelial cells of pericoronal follicles.

Science.gov (United States)

Cimadon, Natalia; Lauxen, Isabel Silva; Carrard, Vinicius Coelho; Sant'Ana Filho, Manoel; Rados, Pantelis Varvaki; Oliveira, Márcia Gaiger

2014-11-01

To evaluate the proliferative potential and the cell proliferation rate of odontogenic epithelial cells. Forty-two cases of pericoronal follicles of impacted third molars were submitted to silver impregnation technique for quantification of argyrophilic nucleolar organizer regions (AgNOR) and immunohistochemical staining for EGFR and Ki-67. For AgNOR quantification, the mean number of active nucleolar organizer regions per nucleus (mAgNOR) and the percentage of cells with 1, 2, 3 and 4 or more AgNORs per nucleus (pAgNOR) were quantified. Ki-67 immunolabeling was quantified, whereas for EGFR, a descriptive analysis of staining patterns (membrane, cytoplasm or membrane + cytoplasm positivity) was performed. We evaluated the reduced epithelium of the enamel organ and/or islands of odontogenic epithelium present in the entire connective tissue. mAgNOR were 1.43 (1.0-2.42) and were significantly different among pericoronary follicles from upper and lower teeth (p = 0.041). Immunostaining of Ki-67 was negative in all cases. EGFR immunolabeling was found mainly in the cytoplasm and was more intense in islands and cords when compared to reduced epithelium of the enamel organ. Odontogenic epithelial cells of some pericoronal follicles have proliferative potential, suggesting their association with the development of odontogenic lesions. The authors suggest that nonerupted, especially of the lower teeth, should be monitored and if necessary removed.

Role of Stromal Paracrine Signals in Proliferative Diseases of the Aging Human Prostate

Directory of Open Access Journals (Sweden)

Kenichiro Ishii

2018-04-01

Full Text Available Androgens are essential for the development, differentiation, growth, and function of the prostate through epithelial–stromal interactions. However, androgen concentrations in the hypertrophic human prostate decrease significantly with age, suggesting an inverse correlation between androgen levels and proliferative diseases of the aging prostate. In elderly males, age- and/or androgen-related stromal remodeling is spontaneously induced, i.e., increased fibroblast and myofibroblast numbers, but decreased smooth muscle cell numbers in the prostatic stroma. These fibroblasts produce not only growth factors, cytokines, and extracellular matrix proteins, but also microRNAs as stromal paracrine signals that stimulate prostate epithelial cell proliferation. Surgical or chemical castration is the standard systemic therapy for patients with advanced prostate cancer. Androgen deprivation therapy induces temporary remission, but the majority of patients eventually progress to castration-resistant prostate cancer, which is associated with a high mortality rate. Androgen deprivation therapy-induced stromal remodeling may be involved in the development and progression of castration-resistant prostate cancer. In the tumor microenvironment, activated fibroblasts stimulating prostate cancer cell proliferation are called carcinoma-associated fibroblasts. In this review, we summarize the role of stromal paracrine signals in proliferative diseases of the aging human prostate and discuss the potential clinical applications of carcinoma-associated fibroblast-derived exosomal microRNAs as promising biomarkers.

PECULIARITIES OF PROLIFERATIVE ACTIVITY OF CERVICAL SQUAMOUS CANCER IN HIV INFECTION.

Science.gov (United States)

Lytvynenko, M; Shkolnikov, V; Bocharova, T; Sychova, L; Gargin, V

2017-09-01

Patients with human immunodeficiency virus (HIV) infection have a statistically significant increased risk of developing cervical cancer. The expression of the human Ki-67 protein is strictly associated with cell proliferation. The purpose of our work was detection of proliferative activity in cervical squamous cancer in women with HIV infection. We investigated 24 cases (12 patients with HIV and 12 patients without HIV infection) of cervical carcinoma, where biopsy had been performed before the treatment. According to histopathological diagnoses, well-differentiated, moderately and poorly differentiated squamous cell carcinoma (7, 13 and 4 cases respectively) was determined. Mean age of women in the group with HIV infection was 32.7 years, and 38.2 years in the group without HIV infection. Detection of protein Ki-67 expression was performed with nuclear staining in the intermediate and superficial cells. The results of this work show that proliferative activity of cervical squamous cancer in women with HIV infection is characterized by a higher level of Ki-67 with averaging level for all histological types of squamous cell carcinoma 62.5±5.6% that is one and half times higher than in group without HIV infection. Depending on a histological type, expression of Ki-67 has increased from 4.7±3.8% in well-differentiated squamous cell carcinoma up to 89.2±5.1% in poorly differentiated squamous cell carcinoma for group with HIV, and from 21.3±2.4% to 79.4±3.7 in group without HIV.

Treatment effects of captopril on non-proliferative diabetic retinopathy

Institute of Scientific and Technical Information of China (English)

WANG Ning; ZHENG Zhi; JIN Hui-yi; XU Xun

2012-01-01

Background Diabetic retinopathy (DR) is one of the most common complications of diabetes.Angiotensin-converting enzyme inhibitor is thought to play an important role in preventing and treating retinal diseases in animal models of DR.The aim of the present study was to investigate the role of angiotensin-converting enzyme inhibitor (ACEI,captopril) in the treatment of patients with non-proliferative DR.Methods Three hundred and seventeen type 2 diabetic patients (88.05％ of participants) without or with mild to moderate non-proliferative retinopathy were randomly divided into captopril group (n=202) and placebo group (n=115).All subjects received 24-month follow-up.General clinical examinations,including blood pressure and glycated hemoglobin,as well as comprehensive standardized ophthalmic examinations were performed.Color fundus photography and optical coherence tomography (OCT) were used to grade diabetic retinopathy and detect macular edema respectively.Results The levels of blood pressure and glycated hemoglobin in the two groups of patients remained within the normal range during the entire follow-up and no significant difference was found between the initial and last visits,suggesting that ACEI drugs play a protective role on the DR patients independent of its anti-blood pressure role.DR classification showed that 169 eyes (83.66％) remained unchanged and the DR grade of 33 eyes (16.34％) increased in captopril group,while 84 eyes (73.04％) remained unchanged and the grade of 31 eyes (26.96％) increased in placebo group (P=0.024).Captopril treatment improved macular edema in 55.45％ eyes,which was significantly higher than the 37.39％ improvement in placebo group (P=0.002).No significant difference was found in the visual acuity between the two groups (P=0.271).Conclusion Captopril can improve or delay the development of DR and macular edema,which can be used in the early treatment of DR patients with type 2 diabetic mellitus.

Proliferative diabetic retinopathy after vitrectomy early factors affect IOP

Directory of Open Access Journals (Sweden)

Shi-Bo Liu

2013-05-01

Full Text Available AIM:To explore possible causes of early postoperative elevated intraocular pressure caused by proliferative diabetic retinopathy(PDRvitrectomy. METHODS:Totally 72 cases(100 eyeswhich have performed vitrectomy for proliferative diabetic retinopathy were retrospectively analyzed to observe the incidence of postoperative ocular hypertension, and the relevant factors that caused postoperative high intraocular pressure were statistically analyzed. Early postoperative ocular hypertension diagnostic criteria: any time after 2 weeks of non-contact tonometer measured IOP> 25mmHg(1mmHg=0.133kPa. RESULTS:High intraocular pressure after vitrectomy occurred in 27 eyes(27%, the incidence of male and female were 27.27%, 26.79%, the difference was not statistically significant(P>0.05. Eyes filled with balanced liquid filling incidence rate of 30.95%, 6.25%, and the difference was statistically significant(P0.05. Incidences of intraoperative panretinal photocoagulation and additional retinal photocoagulation group were 41%, 20%, and the difference was statistically significant(P<0.05. Preoperative retinopathy of four, five, six groups of incidence were 9.52%, 23.81%, 40.56%, and the groups were statistically significant(P<0.05. Unconsolidated preoperative retinal detachment and retinal detachment incidence rate of 19%, 41%, and the difference was statistically significant(P<0.05. Surgery in the united lens resection with intraoperative unfederated lens the resection group's incidence rate of 34%, 15%, the difference was statistically significant(P<0.05. Logistic regression analysis showed that retinal detachment preoperative and intraoperative intraocular filling were independent risk factors that caused early postoperative ocular hypertension after vitrectomy. CONCLUSION:Post-operative ocular hypertension after PDR vitrectomy is related to preoperative retinal detachment, intraoperative lensectomy, intraoperative intraocular filling, and intraoperative

Antimicrobial and Anti-Proliferative Effects of Skin Mucus Derived from Dasyatis pastinaca (Linnaeus, 1758

Directory of Open Access Journals (Sweden)

Virginia Fuochi

2017-11-01

Full Text Available Resistance to chemotherapy occurs in various diseases (i.e., cancer and infection, and for this reason, both are very difficult to treat. Therefore, novel antimicrobial and chemotherapic drugs are needed for effective antibiotic therapy. The aim of the present study was to assess the antimicrobial and anti-proliferative effects of skin mucus derived from Dasyatis pastinaca (Linnaeus, 1758. Our results showed that skin mucus exhibited a significant and specific antibacterial activity against Gram-negative bacteria but not against Gram-positive bacteria. Furthermore, we also observed a significant antifungal activity against some strains of Candida spp. Concerning anti-proliferative activity, we showed that fish mucus was specifically toxic for acute leukemia cells (HL60 with an inhibition of proliferation in a dose dependent manner (about 52% at 1000 μg/mL of fish skin mucous, FSM. Moreover, we did not observe effects in healthy cells, in neuroblastoma cells (SH-SY5Y, and multiple myeloma cell lines (MM1, U266. Finally, it exhibited strong expression and activity of chitinase which may be responsible, at least in part, for the aforementioned results.

THE BIOTIC FACTOR OF TREMATOD OPISTHORHIS FELINEUS INVASION INFLUENCE ON HOST IMMUNE STATUS AND SOMATIC CELLS PROLIFERATIVE ACTIVITY

Directory of Open Access Journals (Sweden)

A. G. Rybka

2016-01-01

Full Text Available The paper confirms long-time opisthorhis invasion role as a risk factor of host immune system reconstitution as well as an important factor in holangiocarcinomas development. It was shown that opisthorhosis invasion primal stage induce host immune system reconstitution. Host immune B-cells system is activated by metacercaria antigens, while the same antigens inhibits T-cells activity. Opisthorhis metabolites stimulate proliferative mithogen-induced T-cells acti vity. Chronic opisthorchis invasion leads to immune system disbalance. It means: decrease of specific and non-speci fic natural killers activity, number of high proliferative activity T-lymphocytes and the shift of regulatory T-cells subset to suppressors prevalence. At the same time specific as well as non-specific T-suppressors functional ability is very low. It was shown T-cells helper-amplifier activation. Despite of circulating B-cells decrease the antibody produced cells number is spleen increases significantly at the same time with circulating immune complexes accumulation. Even 3–6 month after dehelmintisation the immune system disbalance decreases but lefts. In addition, chronic opisthorhis invasion leads to the proliferative processes activation in ductal epithelium, liver, lymph nodes and in other organs which leads to cancer proliferation. According to the results obtained the opisthorhis infected patients needs to be immunocorrected before as well as after dehelmintisation for holangiocancerogenesis profylaxis.

Effect of exercise on the pulmonary system in proliferative phase of menstrual cycle in a group of perimenopausal women

Directory of Open Access Journals (Sweden)

Amrith Pakkala

2014-01-01

Full Text Available Background: Hormonal levels influence dynamic lung function parameters. Significant increase in both progesterone (37% and estradiol (13.5%; where as, no change in plasma follicle stimulating hormone (FSH and luteinizing hormone (LH was observed in exercising women in previous studies. Therefore, this study was intended to see the limitations of the pulmonary system in adaptability to exercise in proliferative phase of menstrual cycle in perimenopausal women. Material and Methods: The present study was conducted as a part of cardiopulmonary efficiency studies on two groups of nonathletes (n = 10 and athletes (n = 10 comparable in age and sex. Menstrual history was ascertained to confirm proliferative phase of menstrual cycle. Dynamic lung functions were measured in both groups before exercise and immediately after exercise. Results: It was observed that exercise per se does not cause a statistically significant change in dynamic lung function parameters maximum mid-expiratory flow (MMEF, peak expiratory flow rate (PEFR, and MEF 25-75% in either of the groups. Conclusion: This finding supports the hypothesis that the respiratory system is not normally the most limiting factor in the delivery of oxygen even under the predominant influence of estrogen in proliferative phase, which is further accentuated by exercise.

The effect of irradiation on function in self-renewing normal tissues with differing proliferative organisation

International Nuclear Information System (INIS)

Wheldon, T.E.; Michalowski, A.S.

1982-01-01

The primary effect of irradiation on self-renewing normal tissues is sterilisation of their proliferative cells, but how this translates into failure of tissue function depends on the mode of organisation of the tissue concerned. It has recently been suggested (Michalowski, 1981) that proliferative normal tissues may be classed as ''hierarchical'' (like haemopoietic tissues) or as ''flexible'' (like liver parenchyma) and that radiation injury to tissue function develops by different pathways in these tissues. Mathematical model studies confirm the different radiation responses of differently organized tissues. Tissues of the ''flexible'' or ''F-type'' category display a variety of novel radiobiological properties, different from those of the more familiar ''hierarchical'' or ''H-type'' tissues. The ''F-type'' responses are strongly influenced by radiation-sterilised (''doomed'') cells, and is is suggested that the role of ''doomed'' cells has been undervalued relative to that of clonogenic survivors. Since ''F-type'' tissues have characteristically low rates of cell renewal, it is possible that these tissues are preferentially responsible for late effects of irradiation in clinical radiotherapy. (author)

Karyopherin alpha2 is essential for rRNA transcription and protein synthesis in proliferative keratinocytes.

Directory of Open Access Journals (Sweden)

Noriko Umegaki-Arao

Full Text Available Karyopherin proteins mediate nucleocytoplasmic trafficking and are critical for protein and RNA subcellular localization. Recent studies suggest KPNA2 expression is induced in tumor cells and is strongly associated with prognosis, although the precise roles and mechanisms of KPNA2 overexpression in proliferative disorders have not been defined. We found that KPNA2 expression is induced in various proliferative disorders of the skin such as psoriasis, Bowen's disease, actinic keratosis, squamous cell carcinoma, Paget's disease, Merkel cell carcinoma, and mycosis fungoides. siRNA-mediated KPNA suppression revealed that KPNA2 is essential for significant suppression of HaCaT proliferation under starvation conditions. Ribosomal RNA transcription and protein synthesis were suppressed by starvation combined with knockdown of KPNA (including KPNA2 expression. KPNA2 localized to the nucleolus and interacted with proteins associated with mRNA processing, ribonucleoprotein complex biogenesis, chromatin modification, and transcription, as demonstrated by tandem affinity purification and mass spectrometry. KPNA2 may be an important promoter of ribosomal RNA and protein synthesis in tumor cells.

Evaluation of viability and proliferative activity of human urothelial cells cultured onto xenogenic tissue-engineered extracellular matrices.

LENUS (Irish Health Repository)

Davis, Niall F

2011-04-01

To evaluate the viability and proliferative activity of human urothelial cells (HUCs) cultured on tissue-engineered extracellular matrix scaffolds and to assess the potential of extracellular matrixes to support the growth of HUCs in their expected in vivo urine environment.

Anti-proliferative and mutagenic activities of aqueous and methanol extracts of leaves from Pereskia bleo (Kunth) DC (Cactaceae).

Science.gov (United States)

Er, Hui Meng; Cheng, En-Hsiang; Radhakrishnan, Ammu Kutty

2007-09-25

The anti-proliferative effects of the aqueous and methanol extracts of leaves of Pereskia bleo (Kunth) DC (Cactaceae) against a mouse mammary cancer cell line (4T1) and a normal mouse fibroblast cell line (NIH/3T3) were evaluated under an optimal (in culture medium containing 10% foetal bovine serum (FBS)) and a sub-optimal (in culture medium containing 0.5% FBS) conditions. Under the optimal condition, the aqueous extract showed a significant (pCactaceae) do not have appreciable anti-proliferative effect on the 4T1 and NIH/3T3 cells as the EC(50) values obtained are greater than 50 microg/mL when tested under optimal culture condition. Moreover, the aqueous extract may form mutagenic compound(s) upon the metabolisation by liver enzymes.

Stochastic cellular automata model of neurosphere growth: Roles of proliferative potential, contact inhibition, cell death, and phagocytosis.

Science.gov (United States)

Sipahi, Rifat; Zupanc, Günther K H

2018-05-14

Neural stem and progenitor cells isolated from the central nervous system form, under specific culture conditions, clonal cell clusters known as neurospheres. The neurosphere assay has proven to be a powerful in vitro system to study the behavior of such cells and the development of their progeny. However, the theory of neurosphere growth has remained poorly understood. To overcome this limitation, we have, in the present paper, developed a cellular automata model, with which we examined the effects of proliferative potential, contact inhibition, cell death, and clearance of dead cells on growth rate, final size, and composition of neurospheres. Simulations based on this model indicated that the proliferative potential of the founder cell and its progenitors has a major influence on neurosphere size. On the other hand, contact inhibition of proliferation limits the final size, and reduces the growth rate, of neurospheres. The effect of this inhibition is particularly dramatic when a stem cell becomes encapsulated by differentiated or other non-proliferating cells, thereby suppressing any further mitotic division - despite the existing proliferative potential of the stem cell. Conversely, clearance of dead cells through phagocytosis is predicted to accelerate growth by reducing contact inhibition. A surprising prediction derived from our model is that cell death, while resulting in a decrease in growth rate and final size of neurospheres, increases the degree of differentiation of neurosphere cells. It is likely that the cellular automata model developed as part of the present investigation is applicable to the study of tissue growth in a wide range of systems. Copyright © 2018 Elsevier Ltd. All rights reserved.

Apoptotic Cell Death and the Proliferative Capacity of Human Breast Cancers

Directory of Open Access Journals (Sweden)

Gabriele A. Losa

1998-01-01

Full Text Available The proliferative capacity (%S‐phase fraction, DNA ploidy, apoptosis frequency (DNA fragmentation and steroid hormone receptor status (estrogen receptor, ER; progesterone receptor, PR of 110 samples of human breast tissues with ductal invasive carcinoma were measured using biochemical and cytofluorimetric procedures. The DNA fragmentation had a left‐skewed frequency distribution and an overall median value of 1.64%, whilst the median %S‐phase fraction was 8%. The median %DNA fragmentation and %S‐phase fraction were 1.96% and 16% in hyperdiploid tumours (n=29; DNA index >1.1 higher than in hypodiploid tumors (n=10; DNA index 0.96, 0.38% and 7.5%. DNA diploid tumours (n=71 had median %DNA fragmentation and %S‐phase values of 1.68% and 6%, consistently lower than the median values of DNA hyperdiploid tumours. The ER content of hypodiploid tumours was about one half (median: 5.9 fmol/mg the median values in hyperdiploid (10.6 fmol/mg and diploid tumours (14.6 fmol/mg. This may correlate with the lowest frequency of apoptosis in hypodiploid tumours, at least when measured by biochemical methods which only detect cells in the late phases of apoptosis. In contrast, the median PR was lowest in hyperdiploid tumours than in hypo and/or diploid tumours. The %S‐phase/%fragmented DNA ratio for the hypodiploid tumours was 19.7, significantly higher than the ratios for hyperdiploid (8.2 and diploid tumours (3.6. These findings indicated that there is an imbalance between proliferative capacity and cell death or growth arrest in human breast tumours. This imbalance may well be linked to a loss of steroid hormone control.

Proliferative activity and branching morphogenesis in the human prostate: a closer look at pre- and postnatal prostate growth

NARCIS (Netherlands)

Xue, Y.; Sonke, G.; Schoots, C.; Schalken, J.; Verhofstad, A.; de la Rosette, J.; Smedts, F.

2001-01-01

To gain further insight into the molecular cell biologic features of prostate development, we investigated the proliferative activity of prostate epithelial and stromal cells and their topographic relationship with neuroendocrine (NE) cell distribution and regional heterogeneity. Consecutive

Proliferative activity and branching morphogenesis in the human prostate: a closer look at pre- and postnatal prostate growth.

NARCIS (Netherlands)

Xue, Y.; Sonke, G.S.; Schoots, C.; Schalken, J.A.; Verhofstad, A.A.J.; Rosette, J.J.M.H.C. de la; Smedts, F.

2001-01-01

BACKGROUND: To gain further insight into the molecular cell biologic features of prostate development, we investigated the proliferative activity of prostate epithelial and stromal cells and their topographic relationship with neuroendocrine (NE) cell distribution and regional heterogeneity.

Trends in pulmonary valve replacement in children and adults with tetralogy of fallot.

Science.gov (United States)

O'Byrne, Michael L; Glatz, Andrew C; Mercer-Rosa, Laura; Gillespie, Matthew J; Dori, Yoav; Goldmuntz, Elizabeth; Kawut, Steven; Rome, Jonathan J

2015-01-01

Operative correction of tetralogy of Fallot frequently results in pulmonary insufficiency and chronic volume overload, which have been linked to increased risk for adverse outcomes. No consensus recommendations for the timing of pulmonary valve replacement (PVR) exist. The aim of this study was to examine the pattern of PVR in the United States from 2004 to 2012. The Pediatric Health Information Systems database was used to perform an observational study of children and adults ≥10 years of age with diagnoses of tetralogy of Fallot who underwent PVR at 35 centers in the United States from 2004 and 2012, to assess the rate of PVR and the age at which is performed. Mixed-effects multivariate regression was used to account for patient-level covariates and center-level covariance. Additional analyses assessed for trends in cost, hospital length of stay (LOS), intensive care unit LOS, and in-hospital mortality over the study period. In total, 799 subjects at 35 centers underwent PVR over the study period. The number of PVRs performed per year increased significantly over the study period. There was significant between-center heterogeneity in age at PVR (p optimal timing of PVR. Copyright © 2015 Elsevier Inc. All rights reserved.

VISUALIZATION FROM INTRAOPERATIVE SWEPT-SOURCE MICROSCOPE-INTEGRATED OPTICAL COHERENCE TOMOGRAPHY IN VITRECTOMY FOR COMPLICATIONS OF PROLIFERATIVE DIABETIC RETINOPATHY.

Science.gov (United States)

Gabr, Hesham; Chen, Xi; Zevallos-Carrasco, Oscar M; Viehland, Christian; Dandrige, Alexandria; Sarin, Neeru; Mahmoud, Tamer H; Vajzovic, Lejla; Izatt, Joseph A; Toth, Cynthia A

2018-01-10

To evaluate the use of live volumetric (4D) intraoperative swept-source microscope-integrated optical coherence tomography in vitrectomy for proliferative diabetic retinopathy complications. In this prospective study, we analyzed a subgroup of patients with proliferative diabetic retinopathy complications who required vitrectomy and who were imaged by the research swept-source microscope-integrated optical coherence tomography system. In near real time, images were displayed in stereo heads-up display facilitating intraoperative surgeon feedback. Postoperative review included scoring image quality, identifying different diabetic retinopathy-associated pathologies and reviewing the intraoperatively documented surgeon feedback. Twenty eyes were included. Indications for vitrectomy were tractional retinal detachment (16 eyes), combined tractional-rhegmatogenous retinal detachment (2 eyes), and vitreous hemorrhage (2 eyes). Useful, good-quality 2D (B-scans) and 4D images were obtained in 16/20 eyes (80%). In these eyes, multiple diabetic retinopathy complications could be imaged. Swept-source microscope-integrated optical coherence tomography provided surgical guidance, e.g., in identifying dissection planes under fibrovascular membranes, and in determining residual membranes and traction that would benefit from additional peeling. In 4/20 eyes (20%), acceptable images were captured, but they were not useful due to high tractional retinal detachment elevation which was challenging for imaging. Swept-source microscope-integrated optical coherence tomography can provide important guidance during surgery for proliferative diabetic retinopathy complications through intraoperative identification of different complications and facilitation of intraoperative decision making.

GENE EXPRESSION CHANGES AND ANTI-PROLIFERATIVE EFFECT OF NONI (Morinda citrifolia FRUIT EXTRACT ANALYSED BY REAL TIME-PCR

Directory of Open Access Journals (Sweden)

hermansyah hermansyah

2017-05-01

Full Text Available To elucidate the anti-proliferative effect of noni (Morinda citrifolia fruit extract for a Saccharomyces cerevisiae model organism, analysis of gene expression changes related to cell cycle associated with inhibition effect of noni fruit extract was carried out. Anti-proliferative of noni fruit extract was analyzed using gene expression changes of Saccharomyces cerevisiae (strains FY833 and BY4741.  Transcriptional analysis of genes that play a role in cell cycle was conducted by growing cells on YPDAde broth medium containing 1% (w/v noni fruit extract, and then subjected using quantitative real-time polymerase chain reaction (RT-PCR.  Transcriptional level of genes CDC6 (Cell Division Cycle-6, CDC20 (Cell Division Cycle-20, FAR1 (Factor ARrest-1, FUS3 (FUSsion-3, SIC1 (Substrate/Subunit Inhibitor of Cyclin-dependent protein kinase-1, WHI5 (WHIskey-5, YOX1 (Yeast homeobOX-1 and YHP1 (Yeast Homeo-Protein-1 increased, oppositely genes expression of DBF4 (DumbBell Forming, MCM1 (Mini Chromosome Maintenance-1 and TAH11 (Topo-A Hypersensitive-11 decreased, while the expression level of genes CDC7 (Cell Division Cycle-7, MBP1 (MIul-box Binding Protein-1 and SWI6 (SWItching deficient-6 relatively unchanged. These results indicated that gene expression changes might associate with anti-proliferative effect from noni fruit extract. These gene expressions changes lead to the growth inhibition of S.cerevisiae cell because of cell cycle defect.

Japan turns pro-life: recent change in reproductive health policy and challenges by new technologies

OpenAIRE

Okamoto, Etsuji

2014-01-01

Japan, known as a pro-choice country in terms of abortion, is currently facing the increase of “selective abortions” thanks to new prenatal screening. Efforts to restrict proliferation of new technology has not been successful and it is likely that Japan will turn pro-life by strictly enforcing the Maternity Protection Act (MPA), which prohibits abortions due to “fetal cause”.

Potent anti-proliferative effects against oral and cervical cancers of Thai medicinal plants selected from the Thai/Lanna medicinal plant recipe database "MANOSROI III".

Science.gov (United States)

Manosroi, Aranya; Akazawa, Hiroyuki; Pattamapun, Kassara; Kitdamrongtham, Worapong; Akihisa, Toshihiro; Manosroi, Worapaka; Manosroi, Jiradej

2015-07-01

Thai/Lanna medicinal plant recipes have been used for the treatment of several diseases including oral and cervical cancers. To investigate anti-proliferative activity on human cervical (HeLa) and oral (KB) cancer cell lines of medicinal plants selected from Thai/Lanna medicinal plant recipe database "MANOSROI III". Twenty-three methanolic plant crude extracts were tested for phytochemicals and anti-proliferative activity on HeLa and KB cell lines for 24 h by the sulforhodamine B (SRB) assay at the doses of 1 × 10(1)-1 × 10(-6 )mg/ml. The nine extracts with the concentrations giving 50% growth inhibition (GI50) lower than 100 µg/ml were further semi-purified by liquid/liquid partition in order to evaluate and enhance the anti-proliferative potency. All extracts contained steroids/triterpenoids, but not xanthones. The methanolic extracts of Gloriosa superba L. (Colchinaceae) root and Albizia chinensis (Osbeck) Merr. (Leguminosae-Mimosoideae) wood gave the highest anti-proliferative activity on HeLa and KB cell lines with the GI50 values of 0.91 (6.0- and 0.31-fold of cisplatin and doxorubicin) and 0.16 µg/ml (28.78- and 82.29-fold of cisplatin and doxorubicin), respectively. Hexane and methanol-water fractions of G. superba exhibited the highest anti-proliferative activity on HeLa and KB cell lines with the GI50 values of 0.15 (37- and 1.9-fold of cisplatin and doxorubicin) and 0.058 µg/ml (77.45- and 221.46-fold of cisplatin and doxorubicin), respectively. This study has demonstrated the potential of plants selected from MANOSROI III database especially G. superba and A. chinensis for further development as anti-oral and cervical cancer agents.

Vitrectomy with and without scleral buckling for retinal detachment Vitrectomia com e sem "scleral buckling" para descolamento da retina

Directory of Open Access Journals (Sweden)

Rubens Camargo Siqueira

2007-03-01

Full Text Available PURPOSE: To compare the surgical results of vitrectomy with and without scleral buckling for rhegmatogenous retinal detachment (RD. METHODS: Fifty-one patients with rhegmatogenous retinal detachment with proliferative vitreoretinopathy (PVR at different stages were submitted to pars plana vitrectomy as the primary surgery, 23 patients (45.09% with scleral buckle (group I and 28 (54.90% without scleral buckle (group II. Visual acuity, anterior segment complications, intraocular pressure, strabismus and retina reattachment rate were evaluated in both groups. RESULTS: The anatomical success and postoperative complications were similar in both groups. Retinal reattachment was achieved in 20 of 23 eyes (87% of group I and in 24 of 28 eyes (85.7% of group II after the initial surgery (p=1.000. Elevated intraocular pressure was noted in 2 eyes (8.7% of group I and 1 eye (3.6% of group II (p=0.583. Corneal abnormalities were seen in 3 eyes (13% of group I and 2 eyes (7.19% of the group II (p=0.647. Visual acuity improved from a preoperative median of 20/200 to a median of 20/100 in group 1 and from 20/400 to 20/100 in group 2; the difference between the two groups was statistically significant (pOBJETIVOS: Comparar os resultados cirúrgicos da vitrectomia com e sem "buckle" escleral para descolamento da retina regmatogênico (DR. MÉTODOS: Cinqüenta e um pacientes com descolamento da retina regmatogênico com proliferação vitreorretiniana (PVR em diferentes estádios foram submetidos a vitrectomia pars plana como cirurgia primária; 23 pacientes (45,09% com buckle escleral (grupo 1 e 28 pacientes (54,90% sem "buckle" escleral (grupo 2. Acuidade visual, complicações do segmento anterior, pressão intra-ocular, estrabismo e razão do redescolamento da retina foram avaliados em ambos os grupos. RESULTADOS: O sucesso anatômico e complicações pós-operatórias foram semelhantes em ambos os grupos. A reaplicação da retina foi obtida em 20 dos 23

Anticardiolipin antibodies in proliferative diabetic retinopathy: An additional risk factor

International Nuclear Information System (INIS)

Shahin, Maha; ElDiasty, Amany M; Mabed, Mohamed

2009-01-01

To report the prevalence of anticardiolipin antibodies in patients with proliferative diabetic retinopathy (PDR) having high-risk criteria (HRC). Diabetic patients having PDR with HRC and diabetics free of retinopathy were compared for the presence of anticardiolipin antibodies. Among the 34 patients, 6 (17.7%) of diabetics having PDR with HRC were positive for anticardiolipin antibodies. There was no significant association of aCL antibodies with sex or type of diabetes. Using Pearson's correlation test, no significant associations of aCL antibodies with duration of diabetes or age of patients were found. All patients who were positive for anticardiolipin antibodies had PDR with HRC. The difference was statistically significant. Presence of anticardiolipin antibodies may represent an additional risk factor for PDR. (author)

Leptin: A proliferative factor for breast cancer?

International Nuclear Information System (INIS)

Caldefie-Chezet, F.; Damez, M.; Latour, M. de; Konska, G.; Mishellani, F.; Fusillier, C.; Guerry, M.; Penault-Llorca, F.; Guillot, J.; Vasson, M.-P.

2005-01-01

Mammary adipose tissue is an important source of paracrine mitogens and anti-mitogens, including insulin-like growth factor, transforming growth factors, and cytokines (especially, TNFα and IL-1β). Nevertheless, it is also an important source of the adipocytokine, leptin. Recently, leptin was reported to stimulate the proliferation of various cell types (pancreatic β cells, prostate, colorectal, lung, etc.) as a new growth factor. It was also shown to stimulate the proliferation of breast cancer cell lines. In this study, we conducted an immunohistochemical analysis of leptin expression in normal tissue and benign and malignant ductal breast cell, representing the different states of the invasion process. We determined for the first time that leptin is expressed both by ductal breast tumors and by benign lesions as atypical hyperplasia. This suggests that leptin may be taken up or synthesized by all modified ductal breast cells, and may prove a proliferative factor. Moreover, leptin is unexpressed by normal tissue in the healthy breast but is exhibited by the normal tissue in near vicinity of the malignant ductal breast lesions. We also postulated that leptin may be a prognostic or diagnostic factor for ductal breast cancer. These putative hypotheses require further study

Echography of the Cervix and Uterus during the Proliferative and Secretory Phases of the Menstrual Cycle in Bonnet Monkeys (Macaca radiata)

Science.gov (United States)

Chaudhari, Uddhav K; Metkari, Siddnath M; Manjaramkar, Dhyananjay D; Sachdeva, Geetanjali; Katkam, Rajendra; Bandivdekar, Atmaram H; Mahajan, Abhishek; Thakur, Meenakshi H; Kholkute, Sanjiv D

2014-01-01

We undertook the present study to investigate the echographic characteristics of the uterus and cervix of female bonnet monkeys (Macaca radiata) during the proliferative and secretory phases of the menstrual cycle. The cervix was tortuous in shape and measured 2.74 ± 0.30 cm (mean ± SD) in width by 3.10 ± 0.32 cm in length. The cervical lumen contained 2 or 3 colliculi, which projected from the cervical canal. The echogenicity of cervix varied during proliferative and secretory phases. The uterus was pyriform in shape (2.46 ± 0.28 cm × 1.45 ± 0.19 cm) and consisted of serosa, myometrium, and endometrium. The endometrium generated a triple-line pattern; the outer and central lines were hyperechogenic, whereas the inner line was hypoechogenic. The endometrium was significantly thicker during the secretory phase (0.69 ± 0.12 cm) than during the proliferative phase (0.43 ± 0.15 cm). Knowledge of the echogenic changes in the female reproductive organs of bonnet monkeys during a regular menstrual cycle may facilitate understanding of other physiologic and pathophysiologic changes. PMID:24411775

Increased T cell proliferative responses to islet antigens identify clinical responders to anti-CD20 monoclonal antibody (rituximab) therapy in type 1 diabetes.

Science.gov (United States)

Herold, Kevan C; Pescovitz, Mark D; McGee, Paula; Krause-Steinrauf, Heidi; Spain, Lisa M; Bourcier, Kasia; Asare, Adam; Liu, Zhugong; Lachin, John M; Dosch, H Michael

2011-08-15

Type 1 diabetes mellitus is believed to be due to the autoimmune destruction of β-cells by T lymphocytes, but a single course of rituximab, a monoclonal anti-CD20 B lymphocyte Ab, can attenuate C-peptide loss over the first year of disease. The effects of B cell depletion on disease-associated T cell responses have not been studied. We compare changes in lymphocyte subsets, T cell proliferative responses to disease-associated target Ags, and C-peptide levels of participants who did (responders) or did not (nonresponders) show signs of β-cell preservation 1 y after rituximab therapy in a placebo-controlled TrialNet trial. Rituximab decreased B lymphocyte levels after four weekly doses of mAb. T cell proliferative responses to diabetes-associated Ags were present at baseline in 75% of anti-CD20- and 82% of placebo-treated subjects and were not different over time. However, in rituximab-treated subjects with significant C-peptide preservation at 6 mo (58%), the proliferative responses to diabetes-associated total (p = 0.032), islet-specific (p = 0.048), and neuronal autoantigens (p = 0.005) increased over the 12-mo observation period. This relationship was not seen in placebo-treated patients. We conclude that in patients with type 1 diabetes mellitus, anti-B cell mAb causes increased proliferative responses to diabetes Ags and attenuated β-cell loss. The way in which these responses affect the disease course remains unknown.

Outcomes of pulmonary valve replacement in 170 patients with chronic pulmonary regurgitation after relief of right ventricular outflow tract obstruction: implications for optimal timing of pulmonary valve replacement.

Science.gov (United States)

Lee, Cheul; Kim, Yang Min; Lee, Chang-Ha; Kwak, Jae Gun; Park, Chun Soo; Song, Jin Young; Shim, Woo-Sup; Choi, Eun Young; Lee, Sang Yun; Baek, Jae Suk

2012-09-11

The objectives of this study were to evaluate outcomes of pulmonary valve replacement (PVR) in patients with chronic pulmonary regurgitation (PR) and to better define the optimal timing of PVR. Although PVR is effective in reducing right ventricular (RV) volume overload in patients with chronic PR, the optimal timing of PVR is not well defined. A total of 170 patients who underwent PVR between January 1998 and March 2011 for chronic PR were retrospectively analyzed. To define the optimal timing of PVR, pre-operative and post-operative cardiac magnetic resonance imaging (MRI) data (n = 67) were analyzed. The median age at the time of PVR was 16.7 years. Follow-up completeness was 95%, and the median follow-up duration was 5.9 years. Overall and event-free survival at 10 years was 98% and 70%, respectively. Post-operative MRI showed significant reduction in RV volumes and significant improvement in biventricular function. Receiver-operating characteristic curve analysis revealed a cutoff value of 168 ml/m(2) for non-normalization of RV end-diastolic volume index (EDVI) and 80 ml/m(2) for RV end-systolic volume index (ESVI). Cutoff values for optimal outcome (normalized RV volumes and function) were 163 ml/m(2) for RV EDVI and 80 ml/m(2) for RV ESVI. Higher pre-operative RV ESVI was identified as a sole independent risk factor for suboptimal outcome. Midterm outcomes of PVR in patients with chronic PR were acceptable. PVR should be considered before RV EDVI exceeds 163 ml/m(2) or RV ESVI exceeds 80 ml/m(2), with more attention to RV ESVI. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Japan Turns Pro-Life: Recent Change in Reproductive Health Policy and Controversies over Prenatal Screening

Directory of Open Access Journals (Sweden)

Etsuji Okamoto

2014-02-01

Full Text Available Japan, known as a pro-choice country in terms of abortion, is currently facing the increase of “selective abortions” thanks to new prenatal screening. Efforts to restrict proliferation of new technology has not been successful and it is likely that Japan will turn pro-life by strictly enforcing the Maternity Protection Act (MPA, which prohibits abortions due to “fetal cause”.

The Role of MKP-1 in the Anti-Proliferative Effects of Glucocorticoids in Primary Rat Pre-Osteoblasts.

Directory of Open Access Journals (Sweden)

Micheline Sanderson

Full Text Available Glucocorticoid (GC-induced osteoporosis has been attributed to a GC-induced suppression of pre-osteoblast proliferation. Our previous work identified a critical role for mitogen-activated protein kinase (MAPK phosphatase-1 (MKP-1 in mediating the anti-proliferative effects of GCs in immortalized pre-osteoblasts, but we subsequently found that MKP-1 null mice were not protected against the pathological effects of GCs on bone. In order to reconcile this discrepancy, we have assessed the effects of GCs on proliferation, activation of the MAPK ERK1/2 and MKP-1 expression in primary adipose-derived stromal cells (ADSCs and ADSC-derived pre-osteoblasts (ADSC-OBs. ADSCs were isolated by means of collagenase digestion from adipose tissue biopsies harvested from adult male Wistar rats. ADSC-OBs were prepared by treating ADSCs with osteoblast differentiation media for 7 days. The effects of increasing concentrations of the GC dexamethasone on basal and mitogen-stimulated cell proliferation were quantified by tritiated thymidine incorporation. ERK1/2 activity was measured by Western blotting, while MKP-1 expression was quantified on both RNA and protein levels, using semi-quantitative real-time PCR and Western blotting, respectively. GCs were strongly anti-proliferative in both naïve ADSCs and ADSC-OBs, but had very little effect on mitogen-induced ERK1/2 activation and did not upregulate MKP-1 protein expression. These findings suggest that the anti-proliferative effects of GCs in primary ADSCs and ADSC-OBs in vitro do not require the inhibition of ERK1/2 activation by MKP-1, which is consistent with our in vivo findings in MKP-1 null mice.

Elevated Subclinical Double-Stranded DNA Antibodies and Future Proliferative Lupus Nephritis

Science.gov (United States)

Lee, Jessica J.; Prince, Lisa K.; Baker, Thomas P.; Papadopoulos, Patricia; Edison, Jess; Abbott, Kevin C.

2013-01-01

Summary Background and objectives Elevated anti–double-stranded DNA (dsDNA) antibody and C-reactive protein are associated with proliferative lupus nephritis (PLN). Progression of quantitative anti-dsDNA antibody in patients with PLN has not been compared with that in patients with systemic lupus erythematosus (SLE) without LN before diagnosis. The temporal relationship between anti-dsDNA antibody and C-reactive protein elevation has also not been evaluated. Design, setting, participants, & measurements This case-control Department of Defense Serum Repository (established in 1985) study compared longitudinal prediagnostic quantitative anti-dsDNA antibody and C-reactive protein levels in 23 patients with biopsy-proven PLN (Walter Reed Army Medical Center, 1993–2009) with levels in 21 controls with SLE but without LN matched for patient age, sex, race, and age of serum sample. The oldest (median, 2601 days; 25%, 1245 days, 75%, 3075 days), the second to last (368; 212, 635 days), and the last (180; 135, 477 days) serum sample before diagnosis were analyzed. Results More patients with PLN had an elevated anti-dsDNA antibody level than did the matched controls at any point (78% versus 5%; P4 years (33% versus 0%; P=0.04) before diagnosis. A rate of increase >1 IU/ml per year (70% versus 0%; P<0.001) was most specific for PLN. The anti-dsDNA antibody levels increased before C-reactive protein did in most patients with an antecedent elevation (92% versus 8%; P<0.001). Conclusions Elevated anti-dsDNA antibody usually precedes both clinical and subclinical evidence of proliferative LN, which suggests direct pathogenicity. Absolute anti-dsDNA antibody level and rate of increase could better establish risk of future PLN in patients with SLE. PMID:23833315

NLRP3 inflammasome activation is associated with proliferative diabetic retinopathy.

Science.gov (United States)

Loukovaara, Sirpa; Piippo, Niina; Kinnunen, Kati; Hytti, Maria; Kaarniranta, Kai; Kauppinen, Anu

2017-12-01

Innate immunity and dysregulation of inflammatory processes play a role in vascular diseases like atherosclerosis or diabetes. Nucleotide-binding domain and Leucine-rich repeat Receptor containing a Pyrin domain 3 (NLRP3) inflammasomes are pro-inflammatory signalling complexes that were found in 2002. In addition to pathogens and other extracellular threats, they can be activated by various endogenous danger signals. The purpose of this study was to find out whether NLRP3 activation occurs in patients with sight-threatening forms of diabetic retinopathy (DR). Inflammasome components NLRP3 and caspase-1, inflammasome-related pro-inflammatory cytokines IL-1β and IL-18, vascular endothelial growth factor (VEGF), acute-phase cytokines TNF-α and IL-6, as well as adaptive immunity-related cytokine interferon gamma (IFN-γ) were measured from the vitreous samples of 15 non-proliferative diabetic retinopathy (non-PDR) and 23 proliferative diabetic retinopathy (PDR) patients using the enzyme-linked immunosorbent assay (ELISA) method. The adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC) was determined using the Western blot technique. Inflammasome components were present in the vitreous of DR patients. Along with VEGF, the levels of caspase-1 and IL-18 were significantly increased, especially in PDR eyes. Interestingly, clearly higher levels of NLRP3 were found in the PDR eyes with tractional retinal detachment (TRD) than from PDR eyes with fully attached retina. There were no significant differences in the amounts of IL-1β, TNF-α, IL-6, and IFN-γ that were detectable in the vitreous of both non-PDR and PDR patients. Our results suggest that NLRP3 inflammasome activation can be associated especially with the pathogenesis of PDR. The lack of differences in TNF-α, IL-6, and IFN-γ also alludes that acute inflammation or T-cell-mediated responses do not dominate in PDR pathogenesis. © 2017 Acta Ophthalmologica Scandinavica Foundation

Ki-67 immunoreactivity in meningiomas--determination of the proliferative potential of meningiomas using the monoclonal antibody Ki-67

DEFF Research Database (Denmark)

Madsen, C; Schrøder, H D

1997-01-01

The proliferative potential of 66 human intracranial meningiomas (15 benign, 15 atypical, 15 recurrent, 13 bone-invasive, and 8 brain-invasive) was investigated by means of immunohisto-chemistry using the monoclonal antibody Ki-67. This antibody recognizes a nuclear antigen present in human cells...

Chromatographic analysis, anti-proliferative and radical scavenging activity of Pinus wallichina essential oil growing in high altitude areas of Kashmir, India.

Science.gov (United States)

Yousuf Dar, Mohd; Shah, Wajaht A; Mubashir, Sofi; Rather, Manzoor A

2012-10-15

To evaluate the in vitro anti-proliferative and radical scavenging properties of the essential oil and its fractions and to determine the chemo-type of P. wallichiana essential oil. Pinus wallichiana oil was extracted by hydro-distillation and fractionated by silica gel column chromatography method. The oil and its fractions were analyzed by Gas chromatography, Gas chromatography-mass spectrometry and (13)C NMR. Different concentrations of oil 12.5, 25, 50 and 100μg/ml and single concentration 50μg/ml of its fractions B(1), B(2), A(2), G(2), Uk(13) and I(2) were evaluated for its anti-proliferative activity by in vitro {3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide} assay against human monocyte, lung carcinoma, liver adenocarcinoma, prostate and ovarian carcinoma, while as the radical scavenging activity was evaluated by different in vitro DPPH assays. The analyses indicated the presence of 17 constituents with β-pinene (46.8%) and α-pinene (25.2%) as major constituents. The oil and its fractions showed significant anti-proliferative activity. The radical scavenging activity also showed good results. The oil could be used as a drug to control the diseases like cancer, cirrhosis and arteriosclerosis, caused by reactive oxygen species. Copyright © 2012 Elsevier GmbH. All rights reserved.

Missed retinal breaks in rhegmatogenous retinal detachment

Directory of Open Access Journals (Sweden)

Brijesh Takkar

2016-12-01

Full Text Available AIM: To evaluate the causes and associations of missed retinal breaks (MRBs and posterior vitreous detachment (PVD in patients with rhegmatogenous retinal detachment (RRD. METHODS: Case sheets of patients undergoing vitreo retinal surgery for RRD at a tertiary eye care centre were evaluated retrospectively. Out of the 378 records screened, 253 were included for analysis of MRBs and 191 patients were included for analysis of PVD, depending on the inclusion criteria. Features of RRD and retinal breaks noted on examination were compared to the status of MRBs and PVD detected during surgery for possible associations. RESULTS: Overall, 27% patients had MRBs. Retinal holes were commonly missed in patients with lattice degeneration while missed retinal tears were associated with presence of complete PVD. Patients operated for cataract surgery were significantly associated with MRBs (P=0.033 with the odds of missing a retinal break being 1.91 as compared to patients with natural lens. Advanced proliferative vitreo retinopathy (PVR and retinal bullae were the most common reasons for missing a retinal break during examination. PVD was present in 52% of the cases and was wrongly assessed in 16%. Retinal bullae, pseudophakia/aphakia, myopia, and horse shoe retinal tears were strongly associated with presence of PVD. Traumatic RRDs were rarely associated with PVD. CONCLUSION: Pseudophakic patients, and patients with retinal bullae or advanced PVR should be carefully screened for MRBs. Though Weiss ring is a good indicator of PVD, it may still be over diagnosed in some cases. PVD is associated with retinal bullae and pseudophakia, and inversely with traumatic RRD.

The anti-proliferative and anti-angiogenic effect of the methanol extract from brittle star.

Science.gov (United States)

Baharara, Javad; Amini, Elaheh; Mousavi, Marzieh

2015-04-01

Anti-angiogenic therapy is a crucial step in cancer treatment. The discovery of new anti-angiogenic compounds from marine organisms has become an attractive concept in anti-cancer therapy. Because little data correlated to the pro- and anti-angiogenic efficacies of Ophiuroidea, which include brittle star, the current study was designed to explore the anti-angiogenic potential of brittle star methanol extract in vitro and in vivo. The anti-proliferative effect of brittle star extract on A2780cp cells was examined by MTT assays, and transcriptional expression of VEGF and b-FGF was evaluated by RT-PCR. In an in vivo model, 40 fertilized Ross eggs were divided into control and three experimental groups. The experimental groups were incubated with brittle star extract at concentrations of 25, 50 and 100 µg/ml, and photographed by photo-stereomicroscopy. Ultimately, numbers and lengths of vessels were measured by Image J software. Data were analyzed with SPSS software (pstar extract exerted a dose- and time-dependent anti-proliferative effect on A2780cp cancer cells. In addition, VEGF and b-FGF expression decreased with brittle star methanol extract treatment. Macroscopic evaluations revealed significant changes in the second and third experimental group compared to controls (pstar methanol extract in vitro and in vivo confer novel insight into the application of natural marine products in angiogenesis-related pathologies.

Frizzled-4 Variations Associated with Retinopathy and Intrauterine Growth Retardation: A Potential Marker for Prematurity and Retinopathy.

Science.gov (United States)

Dailey, Wendy A; Gryc, Wojciech; Garg, Pooja G; Drenser, Kimberly A

2015-09-01

To present the association between mutations affecting the Wnt-signaling receptor protein (FZD4), inherited vitreoretinopathies, and retinopathy of prematurity (ROP). Retrospective analysis of prospective samples at a tertiary referral center. Patients referred to our practice for management of a variety of pediatric vitreoretinopathies were offered participation in an ophthalmic biobank (421 participants with vitreoretinopathies were included in this study). Full-term healthy infants (n = 98) were recruited to the study as controls. Patients with various vitreoretinopathies were prospectively enrolled in an ophthalmic biobank, approved by the Human Investigation Committee at William Beaumont Hospital. Retrospective genetic analysis of the FZD4 gene was performed (Sanger sequencing). Participants with a diagnosis of familial exudative vitreoretinopathy (FEVR), Norrie disease, Coats' disease, bilateral persistent fetal vasculature, and ROP were reviewed for the presence of a FZD4 variant. Data retrieval included status of retinopathy (including staging when possible), gestational age (GA), birth weight (BW) (when available), and family and birth histories. The association of FZD4 variants with the presence of vitreoretinopathy. The sequence variation p.[P33S(;)P168S] is the most prevalent FZD4 variant and is statistically significant for ROP and FEVR (P = 4.6E-04 and P = 2.4E-03, respectively) compared with full-term newborns (P = 1.7E-01). In addition, infants expressing the sequence variation tended to have significantly lower BWs for respective GA (P = 0.04). This suggests that the FZD4 p.[P33S(;)P168S] variant may be a risk factor for retinopathy and restricted intrauterine growth. Testing for FZD4 gene mutations is useful in patients with suspected FEVR and ROP. The relatively high prevalence of the p.[P33S(;)P168S] variant in ROP and intrauterine growth restriction suggests that it also may be a marker for increased risk of developing ROP and preterm birth

Anti-proliferative action of vitamin D in MCF7 is still active after siRNA-VDR knock-down

NARCIS (Netherlands)

J.L. Costa (José); P.P. Eijk (Paul); M.A. van de Wiel (Mark); D. ten Berge (Derk); F. Schmitt (Fernando); C.J. Narvaez (Carmen); J. Welsh; B. Ylstra (Bauke)

2009-01-01

textabstractBackground: The active form of Vitamin D, 1,25-dihydroxyvitamin D3(1,25D), has strong anti-proliferative effects, yet the molecular mechanisms underneath this effect remain unclear. In contrast, the molecular mechanism of 1,25D for the regulation of calcium homeostasis has principally

In vitro anti-proliferative activity of clove extract on human gastric carcinoma

Directory of Open Access Journals (Sweden)

A. Karimi

2017-10-01

Full Text Available Background and objectives: Cancer cell resistance to common chemotherapy agents is on rise. Plants are considered valuable sources of herbal drugs for cancer therapy. The present study was conducted to investigate the in vitro antioxidant, anti-proliferative, and apoptosis-inducing properties of clove (Syzygium aromaticum L. extract in human gastric carcinoma (AGS. Methods: Crude ethanol extract of S. aromaticum dried buds was prepared and  in vitro anti-proliferative effects of the extract on AGS and normal Human dermal fibroblasts (HDF cell lines were studied by MTT assay. To examine apoptosis induction, AGS cells were incubated with IC50 concentrations of the extract, stained with propidium iodide (PI and annexin V-fluorescein isothiocyanate (FITC, and analyzed by flow cytometry. Antioxidant activity and total phenolics and flavonoids contents were evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH assay, Folin-Ciocalteu method, and aluminum chloride colorimetric method, respectively. Results: The IC50 of DPPH and total phenolics and flavonoids contents of the extract were 10.05±1.93 μg/mL, 225.6±40 mg GAE/g, and 29.30±2.35 mgRUT/g, respectively. The IC50 of the extract against HDFs was 649 µg/mL, higher than AGS cells, which was 118.7 g/mL at 48 h after treatment. Flow cytometric analysis showed that the extract induced cell apoptosis. Conclusions: Crude ethanol S. aromaticum extract had high total phenolics content, and suppressed the proliferation of human gastric cancer cells, likely due to apoptosis induction. Further studies should be conducted to determine the mechanisms of its anticancer effects.

Accounting for treatment delays when treating highly proliferative tumours

International Nuclear Information System (INIS)

Jones, L.; Metcalfe, P.; Hoban, P.

1999-01-01

This study was undertaken to investigate the possibility of increasing the dose per fraction or increasing the number of fractions to account for treatment delays occurring during radiotherapy treatments for highly proliferative tumours. The linear quadratic model with time was used to determine the difference in biological effective dose (BED) for the original schedule and the schedule including a treatment delay. Tables of extra fractions and extra dose per fraction required to account for a number of possible delays have been determined. It has been shown that for tumours with very short potential doubling times it is best to deliver the extra dose as an increase in dose per fraction rather than an increase in the number of fractions, while for tumours with moderately short potential doubling times (above 7 days) the reverse is true. The equivalent uninterrupted schedules, which would have delivered the same effects to the tumour, have also been determined. (author)

Inheritance of proliferative breast disease in breast cancer kindreds

International Nuclear Information System (INIS)

Skolnick, M.H.; Cannon-Albright, L.A.; Goldgar, D.E.; Ward, J.H.; Marshall, C.J.; Schumann, G.B.; Hogle, H.; McWhorter, W.P.; Wright, E.C.; Tran, T.D.; Bishop, D.T.; Kushner, J.P.; Eyre, H.J.

1990-01-01

Previous studies have emphasized that genetic susceptibility to breast cancer is rare and is expressed primarily as premenopausal breast cancer, bilateral breast cancer, or both. Proliferative breast disease (PBD) is a significant risk factor for the development of breast cancer and appears to be a precursor lesion. PBD and breast cancer were studied in 103 women from 20 kindreds that were selected for the presence of two first degree relatives with breast cancer and in 31 control women. Physical examination, screening mammography, and four-quadrant fine-needle breast aspirates were performed. Cytologic analysis of breast aspirates revealed PBD in 35% of clinically normal female first degree relatives of breast cancer cases and in 13% of controls. Genetic analysis suggests that genetic susceptibility causes both PBD and breast cancer in these kindreds. This study supports the hypothesis that this susceptibility is responsible for a considerable portion of breast cancer, including unilateral and postmenopausal breast cancer

Wingless promotes proliferative growth in a gradient-independent manner.

Science.gov (United States)

Baena-Lopez, Luis Alberto; Franch-Marro, Xavier; Vincent, Jean-Paul

2009-10-06

Morphogens form concentration gradients that organize patterns of cells and control growth. It has been suggested that, rather than the intensity of morphogen signaling, it is its gradation that is the relevant modulator of cell proliferation. According to this view, the ability of morphogens to regulate growth during development depends on their graded distributions. Here, we describe an experimental test of this model for Wingless, one of the key organizers of wing development in Drosophila. Maximal Wingless signaling suppresses cellular proliferation. In contrast, we found that moderate and uniform amounts of exogenous Wingless, even in the absence of endogenous Wingless, stimulated proliferative growth. Beyond a few cell diameters from the source, Wingless was relatively constant in abundance and thus provided a homogeneous growth-promoting signal. Although morphogen signaling may act in combination with as yet uncharacterized graded growth-promoting pathways, we suggest that the graded nature of morphogen signaling is not required for proliferation, at least in the developing Drosophila wing, during the main period of growth.

[Paediatric retinal detachment and hereditary vitreoretinal disorders].

Science.gov (United States)

Meier, P

2013-09-01

The number of retinal detachments in children is very low in comparison to the number in adults. One predisposing factor for development of paediatric retinal detachment is suffering from hereditary vitreoretinal degeneration (e.g., Stickler syndrome, Wagner syndrome, Kniest dysplasia, familial exudative vitreoretinopathy, congenital X-linked retinoschisis, Knobloch syndrome, incontinentia pigmenti, Norrie disease). Hereditary vitreoretinopathies are characterised by an abnormal-appearing vitreous gel with associated retinal changes. In most of these eyes further ocular abnormalities can be diagnosed. A group of hereditary disorders is associated with characteristic systemic abnormalities. Allied conditions should be considered in the clinical diagnosis. Vitreoretinopathies are the most common cause of inherited retinal detachment. In most eyes primary vitrectomy is necessary, and disease-specific surgical treatment is discussed. Georg Thieme Verlag KG Stuttgart · New York.

Proliferative activity of benign human prostate, prostatic adenocarcinoma and seminal vesicle evaluated by thymidine labeling

International Nuclear Information System (INIS)

Meyer, J.S.; Sufrin, G.; Martin, S.A.

1982-01-01

The thymidine labeling index (TLI) was measured in vitro in the epithelium and stroma of benign prostate glands and seminal vesicles and in the epithelium of prostatic adenocarcinomas. The mean epithelial TLI of normal peripheral (posterior) prostatic zone was 0.12 per cent, and that of the normal central (deep) zone was 0.11 per cent. Mean normal stromal TLI's were 0.08 per cent and 0.06 per cent, respectively. The mean TLI of epithelium in nodular hyperplasia was 0.31 per cent, which differs significantly from normal epithelium, and the mean stromal TLI was also increased. The mean TLI of prostatic adenocarcinomas was 0.90 per cent (range 0.14 to 3.90 per cent) which was significantly higher than for either normal epithelium or epithelium of nodular hyperplasia. Trends of increasing TLI with increasing histologic grades and increasing nuclear size and numbers of nucleoli were not significant. The data support participation of both epithelial and stromal proliferation in nodular hyperplasia, and indicate a low basal proliferative rate in normal prostatic glands. The low TLI's of prostatic adenocarcinomas relative to other malignancies are consistent with their frequently slowly progressive course. The very low proliferative rate of seminal vesicular epithelium may account for the rarity of seminal vesicular carcinomas

ABORTION AND VIOLENCE IN JANE MARTIN’S KEELY AND DU: PRO-CHOICE, PRO-LIFE, OR MERELY PROVOCATIVE?

Directory of Open Access Journals (Sweden)

Eta Farmacelia Nurulhady

2017-04-01

Full Text Available Abortion and violence are global issues, yet different culture might respond to the issues somewhat differently. This study aims to reveal the abortion and violence issues in Jane Martin’s Keely and Du in terms of pro-choice and pro life movements and see how Indonesian students reading the play respond to the issues. In the United States of America, the discussion of abortion issue can be grouped into two major categories: the pro-life and pro-choice. In Indonesia, the majority of people would be against abortion when it is not for medical reasons. The students reading Keely and Du find the play challenging their beliefs as religious people still keeping hold of eastern values. Having discussed the nature of pro-life and pro-choice movements, it is difficult for them to decide whether they are proponent of either one. Keely and Du is successfully provocative in offering insight on how abortion and violence issues cannot be judged in a black and white manner.

Surgical management of retinal diseases: proliferative diabetic retinopathy and traction retinal detachment.

Science.gov (United States)

Cruz-Iñigo, Yousef J; Acabá, Luis A; Berrocal, Maria H

2014-01-01

Current indications for pars plana vitrectomy in patients with proliferative diabetic retinopathy (PDR) include vitreous hemorrhage, tractional retinal detachment (TRD), combined tractional and rhegmatogenous retinal detachment (CTRRD), diabetic macular edema associated with posterior hyaloidal traction, and anterior segment neovascularization with media opacities. This chapter will review the indications, surgical objectives, adjunctive pharmacotherapy, microincision surgical techniques, and outcomes of diabetic vitrectomy for PDR, TRD, and CTRRD. With the availability of new microincision vitrectomy technology, wide-angle microscope viewing systems, and pharmacologic agents, vitrectomy can improve visual acuity and achieve long-term anatomic stability in eyes with severe complications from PDR. © 2014 S. Karger AG, Basel

Lymphocyte proliferative responses to mitogens in rats having an ancestry of a perinatal iodine-131 insult

International Nuclear Information System (INIS)

Stevens, R.H.; Cheng, H.F.

1987-01-01

The possible existence of a genealogical memory consisting of altered lymphocyte proliferative responses to a perinatal iodine-131 insult has been investigated in two generations of inbred Fischer F344 rat offspring. The studies which involved exposure to the radioiodine during late pregnancy with concentrations ranging from 1.85 MBq (50 μCi) to 7.4 MBq (200 μCi) revealed that only the peripheral blood T lymphocytes of the first generation male animals were significantly affected. These animals were found to possess T lymphocytes which exhibited increased proliferative responses expressed toward the mitogens concanavalin A and phytohemagglutin; however, no significant changes were noticeable in their B cell population following exposure to lipopolysaccharide. Neither the first generation females nor the male and female offspring of the second generation developed through sibling interbreeding seemed to be affected, this was unlike the cellular, humoral, and natural immunity which had previously been observed to be changed in both the second and third generation animals. These observations suggest that the effects of the radiation insult upon immunocompetency as measured by lymphocyte proliferation do not appear to be inherited

Progression and Prognosis of Paravalvular Regurgitation After Transcatheter Aortic Valve Implantation

Directory of Open Access Journals (Sweden)

Rafael Alexandre Meneguz-Moreno

2017-11-01

Full Text Available Abstract Background: The impact of paravalvular regurgitation (PVR following transcatheter aortic valve implantation (TAVI remains uncertain. Objective: To evaluate the impact of PVR on mortality and hospital readmission one year after TAVI. Methods: Between January 2009 and June 2015, a total of 251 patients underwent TAVI with three different prostheses at two cardiology centers. Patients were assessed according to PVR severity after the procedure. Results: PVR was classified as absent/trace or mild in 92.0% (n = 242 and moderate/severe in 7.1% (n = 18. The moderate/severe PVR group showed higher levels of aortic calcification (22% vs. 6%, p = 0.03, higher serum creatinine (1.5 ± 0.7 vs. 1.2 ± 0.4 mg/dL, p = 0.014, lower aortic valve area (0.6 ± 0.1 vs. 0.7 ± 0.2 cm2, p = 0.05, and lower left ventricular ejection fraction (49.2 ± 14.8% vs. 58.8 ± 12.1%, p = 0.009. Patients with moderate/severe PVR had more need for post-dilatation (p = 0.025 and use of larger-diameter balloons (p = 0.043. At one year, all-cause mortality was similar in both groups (16.7% vs. 12%, p = 0.08, as well as rehospitalization (11.1% vs. 7.3%, p = 0.915. PVR grade significantly reduced throughout the first year after the procedure (p < 0.01. The presence of moderate/severe PVR was not associated with higher one-year mortality rates (HR: 0.76, 95% CI: 0.27-2.13, p = 0.864, rehospitalization (HR: 1.08, 95% CI: 0.25-4.69, p=0.915, or composite outcome (HR: 0.77, 95% CI: 0.28-2.13, p = 0.613. Conclusion: In this sample, moderate/severe PVR was not a predictor of long-term mortality or rehospitalization. (Arq Bras Cardiol. 2017; [online].ahead print, PP.0-0

SCLERAL BUCKLING VERSUS VITRECTOMY IN THE MANAGEMENT OF MACULA-OFF PRIMARY RHEGMATOGENOUS RETINAL DETACHMENT: A COMPARISON OF VISUAL OUTCOMES.

Science.gov (United States)

Wong, Chee Wai; Yeo, Ian Yew San; Loh, Boon Kwang; Wong, Edmund Yick Mun; Wong, Doric Wen Kuan; Ong, Sze Guan; Ang, Chong Lye; Lee, Shu Yen

2015-12-01

To compare visual outcomes between pars plana vitrectomy (PPV) with or without scleral buckling (SB) and SB alone in the management of uncomplicated macula-off primary rhegmatogenous retinal detachment. Case-control study of 723 patients with uncomplicated macula-off primary rhegmatogenous retinal detachment seen at the Singapore National Eye Centre from 2005 to 2011. The primary outcome measure was the proportion of eyes achieving functional success, defined as logMAR best-corrected visual acuity of ≤0.3 logMAR at 6 months postoperatively. Multivariable logistic regression analysis was performed adjusting for the following preoperative covariates: age, gender, race, lens status, number of tears found, presence of proliferative vitreoretinopathy, operative procedure, logMAR best-corrected visual acuity, and duration of symptoms. Three hundred and eight eyes underwent SB alone, and 415 eyes underwent PPV ± SB. In the SB group, 133 eyes (43.2%) achieved functional success compared with 116 eyes (28.0%) in the PPV ± SB group. This difference was statistically significant on both univariate (P macula-off primary rhegmatogenous retinal detachment.

Synthesis, characterization, in vitro anti-proliferative and hemolytic activity of hydroxyapatite

Science.gov (United States)

Palanivelu, R.; Ruban Kumar, A.

2014-06-01

Hydroxyapatite (Ca10(PO4)6(OH)2, HAP) nanoparticles are widely used in several biomedical applications due to its compositional similarities to bone mineral, excellent biocompatibility and bioactivity, osteoconductivity. In this present investigation, HAP nanoparticles synthesized by precipitation technique using calcium nitrate and di-ammonium phosphate. The crystalline nature and the functional group analysis are confirmed using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and Fourier transform Raman spectroscopy (FT-Raman) respectively. The morphological observations are ascertained from field emission electron scanning electron microscope (FE-SEM) and transmission electron microscope (TEM). In vitro anti-proliferative and hemolytic activities are carried out on the synthesized HAP samples and the studies reveals that HAP have mild activity against erythrocytes.

In vitro anti-proliferative and anti-inflammatory activity of leaf and fruit extracts from Vaccinium bracteatum Thunb

Czech Academy of Sciences Publication Activity Database

Landa, Přemysl; Skálová, L.; Boušová, I.; Kutil, Zsófia; Langhansová, Lenka; Lou, J.D.; Vaněk, Tomáš

2014-01-01

Roč. 27, č. 1 (2014), s. 103-106 ISSN 1011-601X R&D Projects: GA MŠk ME08070 Institutional support: RVO:61389030 Keywords : anti-proliferative activity * anti-inflammatory activity * breast cancer Subject RIV: EI - Biotechnology ; Bionics Impact factor: 0.682, year: 2014 http://www.pjps.pk/wp-content/uploads/pdfs/27/1/Paper-15.pdf

[Effect of low-intensity electromagnetic fields of industrial frequency on the ultrastructure and proliferative activity of rat's thymus cells].

Science.gov (United States)

Zhitkevich, T I; Bokut', T B; Netukova, N I

2001-01-01

Effects of two types of low-intensity electromagnetic fields (EMF) of industrial frequency (50 Hz) on the fine structure and proliferative activity of thymic cells in white rats were studied. It was found that a weak EMF with a prevailing electrical component (380-480 V/m, 120-140 nT1) did not affect the DNA synthesis intensity. An EMF with a stronger magnetic induction (10-15 V/m, 800-1500 nT1) diminished the glucose-6-phosphate dehydrogenase activity and proliferative processes in cultured stimulated lymphocytes. Electron microscopic investigation of the thymus after both types of exposure revealed an accumulation of lymphocytes with pyknotic nuclei and electron-dense cytoplasm, as well as hypoplasia of the vascular endothelium. At the same time, EMF with a prevailing magnetic component produced a more marked negative effect on the ultrastructure of thymic cells, which indicated a lowered secretory activity of epitheliocytes.

Ventricular arrhythmia risk stratification in patients with tetralogy of Fallot at the time of pulmonary valve replacement.

Science.gov (United States)

Sabate Rotes, Anna; Connolly, Heidi M; Warnes, Carole A; Ammash, Naser M; Phillips, Sabrina D; Dearani, Joseph A; Schaff, Hartzell V; Burkhart, Harold M; Hodge, David O; Asirvatham, Samuel J; McLeod, Christopher J

2015-02-01

Most patients with repaired tetralogy of Fallot require pulmonary valve replacement (PVR), but the evaluation for and management of ventricular arrhythmia remain unclear. This study is aimed at clarifying the optimal approach to this potentially life-threatening issue at the time of PVR. A retrospective analysis was performed on 205 patients with repaired tetralogy of Fallot undergoing PVR at our institution between 1988 and 2010. Median age was 32.9 (range, 25.6) years. Previous ventricular tachycardia occurred in 16 patients (8%) and 37 (16%) had left ventricular dysfunction, defined as left ventricular ejection fraction tetralogy of Fallot undergoing PVR with history of ventricular tachycardia or left ventricular dysfunction appear to be associated with a higher risk of arrhythmic events after operation. Events in the first year after PVR are rare, and in select high-risk patients, surgical cryoablation does not seem to increase arrhythmic events and may be protective. © 2014 American Heart Association, Inc.

Cardiac function and central haemodynamics in severe chronic obstructive lung disease. Acute and long-term effects of felodipine

Energy Technology Data Exchange (ETDEWEB)

Bratel, T; Hedenstierna, G; Lundquist, H; Nyquist, O; Ripe, E

1988-01-01

Eleven patients, with advanced chronic obstructive lung disease (COLD), received an infusion of the calcium antagonist felodipine at a rate of 0.9 mg/h. Pulmonary and systemic vascular resistances (PVR and SVR) at rest were reduced by 18% and 33%, respectively. Cardiac output increased by 33%. The right venticular and left venticular ejection fractions (RVEF and LVEF), measured by equilibrium gated radionuclide ventriculography, Increased by 32% and 25%, respectively. During exercise both PVR and SVR fell by a mean of 30%. RVEF and LVEF both increased by about 14%. After three months of oral felopdipine treatment, a dose-related decrease in PVR was noted at rest (r=-0.83) compared with pretreatment values. There was an increase in RVEF which correlated to a reduction in PVR. Three patiens discontinued the trial due to side effects. It is concluded that the reduction of PVR induced by felodipine is accompanied by an improvement in right heart function as measured by ejection fraction measurements.

Long-term follow-up in repaired tetralogy of fallot: can deformation imaging help identify optimal timing of pulmonary valve replacement?

Science.gov (United States)

Sabate Rotes, Anna; Bonnichsen, Crystal R; Reece, Chelsea L; Connolly, Heidi M; Burkhart, Harold M; Dearani, Joseph A; Eidem, Benjamin W

2014-12-01

Novel echocardiographic techniques based on myocardial deformation have not been extensively evaluated to assess right ventricular (RV) and left ventricular (LV) response after pulmonary valve replacement (PVR) in patients with repaired tetralogy of Fallot. Between 2003 and 2012, 133 patients undergoing first-time PVR after tetralogy of Fallot repair underwent echocardiographic assessment at Mayo Clinic. The last echocardiogram before PVR and 1 year after surgery were retrospectively analyzed with Velocity Vector Imaging. Mean age at PVR was 35.5 ± 16.2 years (54% women). Longitudinal peak systolic strain and strain rate before PVR were low: for the left ventricle, -14.8 ± 3.5% and -0.8 ± 0.2 sec(-1), and for the right ventricle, -16.2 ± 4.1% and -0.9 ± 0.3 sec(-1), respectively. There was no significant change in either parameter after surgery. A close correlation between LV and RV deformational parameters was found before PVR and was maintained after surgery. In the multivariate analysis, patients with better LV and RV peak systolic strain preoperatively were found to have better LV and RV peak systolic strain after surgery (P = .004 and P = .006, respectively). However, patients with the most improvement in deformation were those with worse RV function preoperatively (P = .002). Mean New York Heart Association class at early follow-up improved from 2.2 ± 0.8 to 1.2 ± 0.6 (P tetralogy of Fallot undergoing PVR, and there was no significant change after surgery. However, preoperative systolic deformational parameters were predictive of postoperative ventricular function and New York Heart Association class after PVR and may be helpful to identify optimal timing for surgical intervention in this cohort. Copyright © 2014 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

Pulmonary vascular input impedance is a combined measure of pulmonary vascular resistance and stiffness and predicts clinical outcomes better than pulmonary vascular resistance alone in pediatric patients with pulmonary hypertension.

Science.gov (United States)

Hunter, Kendall S; Lee, Po-Feng; Lanning, Craig J; Ivy, D Dunbar; Kirby, K Scott; Claussen, Lori R; Chan, K Chen; Shandas, Robin

2008-01-01

Pulmonary vascular resistance (PVR) is the current standard for evaluating reactivity in children with pulmonary arterial hypertension (PAH). However, PVR measures only the mean component of right ventricular afterload and neglects pulsatile effects. We recently developed and validated a method to measure pulmonary vascular input impedance, which revealed excellent correlation between the zero harmonic impedance value and PVR and suggested a correlation between higher-harmonic impedance values and pulmonary vascular stiffness. Here we show that input impedance can be measured routinely and easily in the catheterization laboratory, that impedance provides PVR and pulmonary vascular stiffness from a single measurement, and that impedance is a better predictor of disease outcomes compared with PVR. Pressure and velocity waveforms within the main pulmonary artery were measured during right heart catheterization of patients with normal pulmonary artery hemodynamics (n = 14) and those with PAH undergoing reactivity evaluation (49 subjects, 95 conditions). A correction factor needed to transform velocity into flow was obtained by calibrating against cardiac output. Input impedance was obtained off-line by dividing Fourier-transformed pressure and flow waveforms. Exceptional correlation was found between the indexed zero harmonic of impedance and indexed PVR (y = 1.095x + 1.381, R2 = 0.9620). In addition, the modulus sum of the first 2 harmonics of impedance was found to best correlate with indexed pulse pressure over stroke volume (y = 13.39x - 0.8058, R2 = 0.7962). Among a subset of patients with PAH (n = 25), cumulative logistic regression between outcomes to total indexed impedance was better (R(L)2 = 0.4012) than between outcomes and indexed PVR (R(L)2 = 0.3131). Input impedance can be consistently and easily obtained from pulse-wave Doppler and a single catheter pressure measurement, provides comprehensive characterization of the main components of RV afterload, and

Cytomorphology of fibrocystic change, high-risk proliferative breast disease, and premalignant breast lesions.

Science.gov (United States)

Masood, Shahla

2005-12-01

In a prospective study using mammographically guided fine needle aspirates in 100 nonpalpable breast lesions, the author's group assessed the reliability of a cytological grading system to define the cytological features of proliferative and nonproliferative breast disease and to differentiate between benign, premalignant and malignant breast lesions. We developed a cytological grading system evaluating the aspirates for the cellular arrangement, the degrees of cellular pleomorphism and anisonucleosis, presence of myoepithelial cells and nucleoli and the status of the chromatin pattern. This grading system, now recognized as the Masood Cytology Index, is commonly used as a surrogate end point biomarker in chemoprevention trials.

Disrupted subject-specific gray matter network properties and cognitive dysfunction in type 1 diabetes patients with and without proliferative retinopathy

NARCIS (Netherlands)

van Duinkerken, Eelco; Ijzerman, Richard G.; Klein, Martin; Moll, Annette C.; Snoek, Frank J.; Scheltens, Philip; Pouwels, Petra J. W.; Barkhof, Frederik; Diamant, Michaela; Tijms, Betty M.

2016-01-01

Type 1 diabetes mellitus (T1DM) patients, especially with concomitant microvascular disease, such as proliferative retinopathy, have an increased risk of cognitive deficits. Local cortical gray matter volume reductions only partially explain these cognitive dysfunctions, possibly because volume

Expression of platelet-derived growth factor and its receptors in proliferative disorders of fibroblastic origin.

OpenAIRE

Smits, A.; Funa, K.; Vassbotn, F. S.; Beausang-Linder, M.; af Ekenstam, F.; Heldin, C. H.; Westermark, B.; Nistér, M.

1992-01-01

Platelet-derived growth factor (PDGF) is known to stimulate the proliferation of connective tissue-derived cells in vitro. Less is known about its functions in vivo, and the role of PDGF in the development of human tumors has not been clarified. The authors have investigated the occurrence of PDGF and PDGF receptors in a series of proliferative disorders of fibroblastic origin using immunohistochemical and in situ hybridization techniques. High expression of PDGF beta-receptor mRNA and protei...

ARTEMIS stabilizes the genome and modulates proliferative responses in multipotent mesenchymal cells

Directory of Open Access Journals (Sweden)

Tompkins Kathleen

2010-10-01

Full Text Available Abstract Background Unrepaired DNA double-stranded breaks (DSBs cause chromosomal rearrangements, loss of genetic information, neoplastic transformation or cell death. The nonhomologous end joining (NHEJ pathway, catalyzing sequence-independent direct rejoining of DSBs, is a crucial mechanism for repairing both stochastically occurring and developmentally programmed DSBs. In lymphocytes, NHEJ is critical for both development and genome stability. NHEJ defects lead to severe combined immunodeficiency (SCID and lymphoid cancer predisposition in both mice and humans. While NHEJ has been thoroughly investigated in lymphocytes, the importance of NHEJ in other cell types, especially with regard to tumor suppression, is less well documented. We previously reported evidence that the NHEJ pathway functions to suppress a range of nonlymphoid tumor types, including various classes of sarcomas, by unknown mechanisms. Results Here we investigate roles for the NHEJ factor ARTEMIS in multipotent mesenchymal stem/progenitor cells (MSCs, as putative sarcomagenic cells of origin. We demonstrate a key role for ARTEMIS in sarcoma suppression in a sensitized mouse tumor model. In this context, we found that ARTEMIS deficiency led to chromosomal damage but, paradoxically, enhanced resistance and proliferative potential in primary MSCs subjected to various stresses. Gene expression analysis revealed abnormally regulated stress response, cell proliferation, and signal transduction pathways in ARTEMIS-defective MSCs. Finally, we identified candidate regulatory genes that may, in part, mediate a stress-resistant, hyperproliferative phenotype in preneoplastic ARTEMIS-deficient MSCs. Conclusions Our discoveries suggest that Art prevents genome damage and restrains proliferation in MSCs exposed to various stress stimuli. We propose that deficiency leads to a preneoplastic state in primary MSCs and is associated with aberrant proliferative control and cellular stress

Serum MiRNA Biomarkers serve as a Fingerprint for Proliferative Diabetic Retinopathy

Directory of Open Access Journals (Sweden)

Shao Qing

2014-11-01

Full Text Available Background: Diabetic retinopathy (DR is a retinopathy resulting from diabetes mellitus (DM which was classified into non-proliferative DR (NPDR and proliferative DR (PDR. Without an early screening and effective diagnosis, patients with PDR will develop serious complications. Therefore, we sought to identify special serum microRNAs (miRNAs that can serve as a novel non-invasive screening signature of PDR and test its specificity and sensitivity in the early diagnosis of PDR. Methods: In total, we obtained serum samples from 90 PDR cases, 90 matched NPDR patients and 20 controls. An initial screening of miRNA expression was performed through TaqMan Low Density Array (TLDA. The candidate miRNAs were validated by individual reverse transcription quantitative real-time PCR (RT-qPCR arranged in an initial and a two-stage validation sets. Moreover, additional double-blind testing was performed in 20 patients clinically suspected of having DR to evaluate the diagnostic value and accuracy of the serum miRNA profiling system in predicting PDR. Results: Three miRNAs were significantly increased in patients with PDR compared with NPDR after the multiple stages. The areas under the receiver operating characteristic (ROC curves of the validated three-serum miRNAs signature were 0.830, 0.803 and 0.873 in the initial and two validation sets, respectively. Combination of miR-21, miR-181c, and miR-1179 possessed a moderate ability to discrimination between PDR and NPDR with an area under ROC value of 0.89. The accuracy rate of the three-miRNA profile as PDR signature was 82.6%. Conclusions: These data provide evidence that serum miRNAs have the potential to be sensitive, cost-effective biomarkers for the early detection of PDR. These biomarkers could serve as a dynamic monitoring factor for detecting the progression of PDR from NPDR.

Poliovirus trafficking toward central nervous system via human poliovirus receptor-dependent and -independent pathway.

Directory of Open Access Journals (Sweden)

Seii eOHKA

2012-04-01

Full Text Available In humans, paralytic poliomyelitis results from the invasion of the central nervous system by circulating poliovirus (PV via the blood-brain barrier (BBB. After the virus enters the central nervous system (CNS, it replicates in neurons, especially in motor neurons (MNs, inducing the cell death that causes paralytic poliomyelitis. Along with this route of dissemination, neural pathway has been reported in humans, monkeys, and PV-sensitive human PV receptor (hPVR/CD155-transgenic (Tg mice. We demonstrated that a fast retrograde axonal transport process is required for PV dissemination through the sciatic nerve of hPVR-Tg mice and that intramuscularly inoculated PV causes paralysis in a hPVR-dependent manner. We also showed that hPVR-independent axonal transport of PV exists in hPVR-Tg and non-Tg mice, indicating that several different pathways for PV axonal transport exist in these mice. Circulating PV after intravenous inoculation in mice cross the BBB at a high rate in a hPVR-independent manner. Recently, we identified transferrin receptor 1 (TfR1 of mouse brain capillary endothelial cells as a binding protein to PV, implicating that TfR1 is a possible receptor for PV to permeate the BBB.

Autologous proliferative therapies in recalcitrant lateral epicondylitis.

Science.gov (United States)

Tetschke, Elisa; Rudolf, Margit; Lohmann, Christoph H; Stärke, Christian

2015-09-01

This study investigates the clinical effects of autologous conditioned plasma (ACP) injections and low-level laser application as therapy options for chronic lateral epicondylitis. A total of 52 patients with chronic lateral epicondylitis were evaluated in this study; 26 of these patients received three ACP injections and the control group, with 26 patients, received 12 laser applications, with standardized physical therapy for all patients afterward. Control examinations took place before treatment, after 2 and 6 mos, and in the 1 yr final follow-up. The control examination included the visual analog scale for pain and Disabilities of the Arm, Shoulder and Hand outcome measure scores. The analysis at final follow-up after 1 yr showed that both treatment options resulted in successful therapy outcome for the patients. In total, 63.5 % were successfully treated. Successful treatment was defined as more than 30% improvement in the visual analog score and more than 10.2 points in the Disabilities of the Arm, Shoulder and Hand score. Both groups showed a significant improvement in time response. This study demonstrates the beneficial effects of autologous proliferative therapies in the treatment of lateral epicondylitis. The data show that laser application and ACP therapy lead to a clinical improvement in epicondylopathia. Especially the new treatment with ACP can be highlighted as an alternative and as an easy-to-apply therapy option for clinical practice.

A senescence rescue screen identifies BCL6 as an inhibitor of anti-proliferative p19ARF-p53 signaling

NARCIS (Netherlands)

Shvarts, A.; Brummelkamp, T.; Koh, E.; Daley, G.Q.; Bernards, R.A.

2002-01-01

Senescence limits the proliferative capacity of primary cells in culture. We describe here a genetic screen to identify genes that allow bypass of this checkpoint. Using retroviral cDNA expression libraries, we identify BCL6 as a potent inhibitor of senescence. BCL6 is frequently activated in

A senescence rescue screen identifies BCL6 as an inhibitor of anti-proliferative p19(ARF)-p53 signaling

NARCIS (Netherlands)

Shvarts, Avi; Brummelkamp, Thijn R.; Scheeren, Ferenc; Koh, Eugene; Daley, George Q.; Spits, Hergen; Bernards, René

2002-01-01

Senescence limits the proliferative capacity of primary cells in culture. We describe here a genetic screen to identify genes that allow bypass of this checkpoint. Using retroviral cDNA expression libraries, we identify BCL6 as a potent inhibitor of senescence. BCL6 is frequently activated in

Proliferative activity of stomach cancer and assessment of individual radiosensitivity

International Nuclear Information System (INIS)

Chissov, V.I.; Sergeeva, N.S.; Dar'yalova, S.L.; Petrov, A.N.; Repina, A.G.; Belous, T.A.; Pelevina, I.I.

1991-01-01

An indirect immunofluorescent method with polyclonal antibodies to thymidine was used to assess the proliferative activity (PA-percent of cells in the S-phase of the cell cycle) of 79 stomach tumors from primary cancer patients. Stomach cancer PA was shown to vary from 0.1 to 69.7%. Stomach cancer PA did not depend either on a tumor size or a degree of the involvement of regional lymph nodes. The mean PA of well-differentiated adenocarcinoma was slightly lower (14.9±4.7%) than that of low differentiated ones. Of 79 patients a tumor process was interpreted as a resectable one in 62. They were given preoperative irradiation at a total focal dose of 36 Gy followed by operation. It was shown that tumor radioresistance could be predicted in unchanged PA indices of their increase at the beginning of a course of irradiation with the probability of 95%

Korean Ginseng Berry Fermented by Mycotoxin Non-producing Aspergillus niger and Aspergillus oryzae: Ginsenoside Analyses and Anti-proliferative Activities.

Science.gov (United States)

Li, Zhipeng; Ahn, Hyung Jin; Kim, Nam Yeon; Lee, Yu Na; Ji, Geun Eog

2016-01-01

To transform ginsenosides, Korean ginseng berry (KGB) was fermented by mycotoxin non-producing Aspergillus niger and Aspergillus oryzae. Changes of ginsenoside profile and anti-proliferative activities were observed. Results showed that A. niger tended to efficiently transform protopanaxadiol (PPD) type ginsenosides such as Rb1, Rb2, Rd to compound K while A. oryzae tended to efficiently transform protopanaxatriol (PPT) type ginsenoside Re to Rh1 via Rg1. Butanol extracts of fermented KGB showed high cytotoxicity on human adenocarcinoma HT-29 cell line and hepatocellular carcinoma HepG2 cell line while that of unfermented KGB showed little. The minimum effective concentration of niger-fermented KGB was less than 2.5 µg/mL while that of oryzae-fermented KGB was about 5 µg/mL. As A. niger is more inclined to transform PPD type ginsenosides, niger-fermented KGB showed stronger anti-proliferative activity than oryzae-fermented KGB.

Breast cancer risk after diagnosis by screening mammography of nonproliferative or proliferative benign breast disease: a study from a population-based screening program.

Science.gov (United States)

Castells, Xavier; Domingo, Laia; Corominas, Josep María; Torá-Rocamora, Isabel; Quintana, María Jesús; Baré, Marisa; Vidal, Carmen; Natal, Carmen; Sánchez, Mar; Saladié, Francina; Ferrer, Joana; Vernet, Mar; Servitja, Sonia; Rodríguez-Arana, Ana; Roman, Marta; Espinàs, Josep Alfons; Sala, María

2015-01-01

Benign breast disease increases the risk of breast cancer. This association has scarcely been evaluated in the context of breast cancer screening programs although it is a prevalent finding in mammography screening. We assessed the association of distinct categories of benign breast disease and subsequent risk of breast cancer, as well as the influence of a family history of breast cancer. A retrospective cohort study was conducted in 545,171 women aged 50-69 years biennially screened for breast cancer in Spain. The median of follow-up was 6.1 years. The age-adjusted rate ratio (RR) of breast cancer for women with benign breast disease, histologically classified into nonproliferative and proliferative disease with and without atypia, compared with women without benign breast disease was estimated by Poisson regression analysis. A stratified analysis by family history of breast cancer was performed in a subsample. All tests were two-sided. The age-adjusted RR of breast cancer after diagnosis of benign breast disease was 2.51 (95 % CI: 2.14-2.93) compared with women without benign breast disease. The risk was higher in women with proliferative disease with atypia (RR = 4.56, 95 % CI: 2.06-10.07) followed by those with proliferative disease without atypia (RR = 3.58; 95 % CI = 2.61-4.91). Women with nonproliferative disease and without a family history of breast cancer remained also at increased risk of cancer (OR = 2.23, 95 % CI: 1.86-2.68). An increased risk of breast cancer was observed among screening participants with proliferative or nonproliferative benign breast disease, regardless of a family history of breast cancer. This information may be useful to explore risk-based screening strategies.

Arctigenin in combination with quercetin synergistically enhances the anti-proliferative effect in prostate cancer cells

Science.gov (United States)

Wang, Piwen; Phan, Tien; Gordon, David; Chung, Seyung; Henning, Susanne M.; Vadgama, Jaydutt V.

2014-01-01

Scope We investigated whether a combination of two promising chemopreventive agents arctigenin and quercetin increases the anti-carcinogenic potency at lower concentrations than necessary when used individually in prostate cancer. Methods and results Androgen-dependent LAPC-4 and LNCaP prostate cancer cells were treated with low doses of arctigenin and quercetin alone or in combination for 48h. The anti-proliferative activity of arctigenin was 10-20 fold stronger than quercetin in both cell lines. Their combination synergistically enhanced the anti-proliferative effect, with a stronger effect in androgen receptor (AR) wild-type LAPC-4 cells than in AR mutated LNCaP cells. Arctigenin demonstrated a strong ability to inhibit AR protein expression in LAPC-4 cells. The combination treatment significantly inhibited both AR and PI3K/Akt pathways compared to control. A protein array analysis revealed that the mixture targets multiple pathways particularly in LAPC-4 cells including Stat3 pathway. The mixture significantly inhibited the expression of several oncogenic microRNAs including miR-21, miR-19b, and miR-148a compared to control. The mixture also enhanced the inhibition of cell migration in both cell lines compared to individual compounds tested. Conclusion The combination of arctigenin and quercetin, that target similar pathways, at low physiological doses, provides a novel regimen with enhanced chemoprevention in prostate cancer. PMID:25380086

Proliferative activity of benign human prostate, prostatic adenocarcinoma and seminal vesicle evaluated by thymidine labeling

International Nuclear Information System (INIS)

Meyer, J.S.; Sufrin, G.; Martin, S.A.

1982-01-01

The thymidine labeling index (TLI) was measured in vitro in the epithelium and stroma of benign prostate glands and seminal vesicles and in the epithelium of prostatic adenocarcinomas. The mean epithelial TLI of normal peripheral (posterior) prostatic zone was 0.12 percent, and that of the normal central (deep) zone was 0.11 percent. Mean normal stromal TLI's were 0.08 percent and 0.06 percent, respectively. The mean TLI of epithelium in nodular hyperplasia was 0.31 percent, which differs significantly from normal epithelium (p less than 0.05), and the mean stromal TLI was also increased (0.16 percent, p less than 0.1). The mean TLI of prostatic adenocarcinomas was 0.90 percent (range 0.14 to 3.90 percent) which was significantly higher than for either normal epithelium (p less than 0.001) or epithelium of nodular hyperplasia (p less than 0.05). Trends of increasing TLI with increasing histologic grades and increasing nuclear size and numbers of nucleoli were not significant. The data support participation of both epithelial and stromal proliferation in nodular hyperplasia, and indicate a low basal proliferative rate in normal prostatic glands. The low TLI's of prostatic adenocarcinomas relative to other malignancies are consistent with their frequently slowly progressive course. The very low proliferative rate of seminal vesicular epithelium (mean TLI 0.02 percent) may account for the rarity of seminal vesicular carcinomas

Anti-Proliferative and Apoptotic Effects of Beta-Ionone in Human Leukemia Cell Line K562

Directory of Open Access Journals (Sweden)

Zohreh Faezizadeh

2016-06-01

Full Text Available Background Beta-ionone is an aroma compound found in the Rosaceae family. Some evidence supported that beta-ionone has a great potential for cancer prevention. To date, the anti-proliferative and apoptotic effects of beta-ionone in human leukemia cell line K562 were not studied. Objectives Hence, we investigated whether beta-ionone could inhibit cell growth and induce apoptosis in the K562 cells. Materials and Methods In this experimental study, human leukemia cell line K562 was cultured and anti-proliferation effect of beta-ionone with different doses (25 - 400 µm at different times (24 - 96 hours on treated cells was evaluated by the MTT assay. To determine apoptosis rate, the Hoechst 33342 staining and flow cytometry was performed. Results The MTT assay showed that beta-ionone inhibited proliferation of K562 cells in a dose-dependent manner significantly (P = 0.0008. Moreover, the increased apoptotic rate was found after incubation of K562 cells with 200 µm beta-ionone. The Hoechst staining and flow cytometry analysis indicated that beta-ionone could increase apoptosis of K562 cells in a dose-dependent manner. Conclusions The results demonstrated that beta-ionone has anti-proliferative and apoptotic effects on K562 cells, and in the future may be used in the treatment of some leukemia sub-types.

Evaluation of in vitro anti-proliferative and immunomodulatory activities of compounds isolated from Curcuma longa

Science.gov (United States)

Yue, Grace G. L.; Chan, Ben C. L.; Hon, Po-Ming; Lee, Mavis Y. H.; Fung, Kwok-Pui; Leung, Ping-Chung; Lau, Clara B. S.

2010-01-01

The rhizome of Curcuma longa (CL) has been commonly used in Asia as a potential candidate for the treatment of different diseases, including inflammatory disorders and cancers. The present study evaluated the anti-proliferative activities of the isolated compounds (3 curcuminoids and 2 turmerones) from CL, using human cancer cell lines HepG2, MCF-7 and MDA-MB-231. The immunomodulatory activities of turmerones (α and aromatic) isolated from CL were also examined using human peripheral blood mononuclear cells (PBMC). Our results showed that the curcuminoids (curcumin, demethoxycurcumin and bisdemethoxycurcumin) and α-turmerone significantly inhibited proliferation of cancer cells in dose-dependent manner. The IC50 values of these compounds in cancer cells ranged from 11.0–41.8 μg/ml. Alpha-turmerone induced MDA-MB-231 cells to undergo apoptosis, which was confirmed by annexin-V & propidium iodide staining, and DNA fragmentation assay. The caspase cascade was activated as shown by a significant decrease of procaspases-3, -8 and -9 in α-turmerone treated cells. Both α-turmerone and aromatic-turmerone showed stimulatory effects on PBMC proliferation and cytokine production. The anti-proliferative effect of α-turmerone and immunomodulatory activities of ar-turmerone were shown for the first time. The findings revealed the potential use of CL crude extract (containing curcuminoids and volatile oil including turmerones) as chemopreventive agent. PMID:20438793

Effects of irradiated diet on longevity and prolificity of successive generations of Zabrotes subfasciatus (Boheman, 1833) (Coleoptera, Bruchidae)

International Nuclear Information System (INIS)

Domarco, R.E.

1981-01-01

The study was done in the laboratory of Entomology of the Centro de Energia Nuclear na Agricultura (CENA), University of Sao Paulo, in Piracicaba, State of Sao Paulo, Brazil. This research was carried out to observe the effect of irradiated beans (Phaseolus vulgaris, (L.), cultivar Rosinha) on the longevity and prolificity of Zabrotes subfasciatus (Boheman, 1833) (Coleoptera, Bruchidae). The first part of the study included the rearing of five generations of Zabrotes subfasciatus which were fed with irradiated beans (0, 10, 20, 100 e 200 krad, with a dose rate of approximately 70 krad/h). The second one consisted of growth of seven generations on irradiated beans (0, 100, 500, 1500 and 3000 krad, with a dose rate of approximately 70 krad/h). The data were obtained through daily countings of insect birth and death rates. It was concluded that irradiation modified the nutritional quality of beans, affecting the development of Zabrotes subfasciatus. This effect was studied through the longevity and prolificity, which were altered as compared with the control, once they were higher for the dosis of 1500 and 3000 krad. (author)

Immunoregulatory activities of human immunodeficiency virus (HIV) proteins: Effect of HIV recombinant and synthetic peptides on immunoglobulin synthesis and proliferative responses by normal lymphocytes

International Nuclear Information System (INIS)

Nair, M.P.N.; Pottathil, R.; Heimer, E.P.; Schwartz, S.A.

1988-01-01

Recombinant and synthetic peptides corresponding to envelope proteins of the human immunodeficiency virus (HIV) were examined for their effects on the activities of lymphocytes from normal donors in vitro. Although lymphocytes cultured with env-gag peptides produced significant amounts of IgG, addition of env-gag peptides to a pokeweed mitogen-induced B-cell activation system resulted in suppression of immunoglobulin synthesis by normal lymphocytes. Recombinant antigens, env-gag and env-80 dihydrofolate reductase (DHFR), produced a substantial proliferative response by peripheral blood mononuclear cells (PBMC) as determined by [ 3 H]thymidine incorporation. PBMC precultured with HIV synthetic peptide env 578-608 also manifested significant proliferative responses as compared to control cultures. CD3 + lymphocytes precultured with recombinant HIV antigens, env-gag and env-80 DHFR, and synthetic HIV peptide, env 487-511, showed moderate but significant proliferative responses. Both recombinant antigens and synthetic peptides also produced a dose-dependent stimulatory effect on proliferation by CD3 - lymphocytes. These studies demonstrate that recombinant and synthetic peptides of the HIV genome express immunoregulatory T- and B-cell epitopes. Identification of unique HIV epitopes with immunogenic and immunoregulatory activities is necessary for the development of an effective vaccine against HIV infection

Curcumin Conjugated with PLGA Potentiates Sustainability, Anti-Proliferative Activity and Apoptosis in Human Colon Carcinoma Cells

Science.gov (United States)

Waghela, Bhargav N.; Sharma, Anupama; Dhumale, Suhashini; Pandey, Shashibahl M.; Pathak, Chandramani

2015-01-01

Curcumin, an ingredient of turmeric, exhibits a variety of biological activities such as anti-inflammatory, anti-atherosclerotic, anti-proliferative, anti-oxidant, anti-cancer and anti-metastatic. It is a highly pleiotropic molecule that inhibits cell proliferation and induces apoptosis in cancer cells. Despite its imperative biological activities, chemical instability, photo-instability and poor bioavailability limits its utilization as an effective therapeutic agent. Therefore, enhancing the bioavailability of curcumin may improve its therapeutic index for clinical setting. In the present study, we have conjugated curcumin with a biodegradable polymer Poly (D, L-lactic-co-glycolic acid) and evaluated its apoptotic potential in human colon carcinoma cells (HCT 116). The results show that curcumin-PLGA conjugate efficiently inhibits cell proliferation and cell survival in human colon carcinoma cells as compared to native curcumin. Additionally, curcumin conjugated with PLGA shows improved cellular uptake and exhibits controlled release at physiological pH as compared to native curcumin. The curcumin-PLGA conjugate efficiently activates the cascade of caspases and promotes intrinsic apoptotic signaling. Thus, the results suggest that conjugation potentiates the sustainability, anti-proliferative and apoptotic activity of curcumin. This approach could be a promising strategy to improve the therapeutic index of cancer therapy. PMID:25692854

Gingival proliferative lesions in children and adolescents in Brazil: A 15-year-period cross-sectional study

Directory of Open Access Journals (Sweden)

Fabiana Caroline daSilva

2016-01-01

Full Text Available Background: Studies assessing the prevalence of oral lesions in children and adolescents, particularly in gingiva are scarce in the literature. The aim of the study was to describe the distribution of gingival proliferative lesions based on clinical and histopathological diagnoses in children and adolescents. Materials and Methods: A review of clinical charts of children and adolescents aged between 0 and 18 years old, admitted to the Oral Medicine Outpatient Unit, of Universidade Federal do Paraná, for 15 years (1994–2009 was performed. Results: Six hundred and sixty-nine out of 5,129 patients treated during this period were aged between 0 and 18 years old, and 45 of these had gingival lesions. The largest number of lesions was observed between 11 and 16 years old. The majority of the patients were referred by Curitiba's public health system. Pyogenic granuloma was the most frequent lesion (19 = 42.2%, followed by peripheral giant cell lesion (11 = 24.4%, gingival fibromatosis (10 = 22.2%, and peripheral ossifying fibroma (5 = 11.1%. Conclusion: Gingival proliferative lesions can show similar clinical characteristics. Appropriate clinical and histopathological diagnoses are necessary to guide the healthcare professional to establish the adequate treatment and to estimate the risk of recurrence.

Proliferative responses of blood mononuclear cells (BMNC) in a cohort of elderly humans: role of lymphocyte phenotype and cytokine production

DEFF Research Database (Denmark)

Bruunsgaard, H.; Pedersen, Agnes Nadelmann; Schroll, M.

2000-01-01

Age-related impaired T cell function is associated with increased mortality risk. The purpose of the present study was therefore to identify factors associated with the age-related decreased phytohaemagglutinin (PHA)-induced proliferative response of lymphocytes in a cohort of 174 81-year...

Automated detection of neovascularization for proliferative diabetic retinopathy screening.

Science.gov (United States)

Roychowdhury, Sohini; Koozekanani, Dara D; Parhi, Keshab K

2016-08-01

Neovascularization is the primary manifestation of proliferative diabetic retinopathy (PDR) that can lead to acquired blindness. This paper presents a novel method that classifies neovascularizations in the 1-optic disc (OD) diameter region (NVD) and elsewhere (NVE) separately to achieve low false positive rates of neovascularization classification. First, the OD region and blood vessels are extracted. Next, the major blood vessel segments in the 1-OD diameter region are classified for NVD, and minor blood vessel segments elsewhere are classified for NVE. For NVD and NVE classifications, optimal region-based feature sets of 10 and 6 features, respectively, are used. The proposed method achieves classification sensitivity, specificity and accuracy for NVD and NVE of 74%, 98.2%, 87.6%, and 61%, 97.5%, 92.1%, respectively. Also, the proposed method achieves 86.4% sensitivity and 76% specificity for screening images with PDR from public and local data sets. Thus, the proposed NVD and NVE detection methods can play a key role in automated screening and prioritization of patients with diabetic retinopathy.

Lactobacillus casei Exerts Anti-Proliferative Effects Accompanied by Apoptotic Cell Death and Up-Regulation of TRAIL in Colon Carcinoma Cells

Science.gov (United States)

Santarmaki, Valentina; Aindelis, Georgios; Tompoulidou, Evgenia; Lamprianidou, Eleftheria E.; Saxami, Georgia; Ypsilantis, Petros; Lampri, Evangeli S.; Simopoulos, Constantinos; Kotsianidis, Ioannis; Galanis, Alex; Kourkoutas, Yiannis; Dimitrellou, Dimitra; Chlichlia, Katerina

2016-01-01

Probiotic microorganisms such as lactic acid bacteria (LAB) exert a number of strain-specific health-promoting activities attributed to their immunomodulatory, anti-inflammatory and anti-carcinogenic properties. Despite recent attention, our understanding of the biological processes involved in the beneficial effects of LAB strains is still limited. To this end, the present study investigated the growth-inhibitory effects of Lactobacillus casei ATCC 393 against experimental colon cancer. Administration of live Lactobacillus casei (as well as bacterial components thereof) on murine (CT26) and human (HT29) colon carcinoma cell lines raised a significant concentration- and time-dependent anti-proliferative effect, determined by cell viability assays. Specifically, a dramatic decrease in viability of colon cancer cells co-incubated with 109 CFU/mL L. casei for 24 hours was detected (78% for HT29 and 52% for CT26 cells). In addition, live L. casei induced apoptotic cell death in both cell lines as revealed by annexin V and propidium iodide staining. The significance of the in vitro anti-proliferative effects was further confirmed in an experimental tumor model. Oral daily administration of 109 CFU live L. casei for 13 days significantly inhibited in vivo growth of colon carcinoma cells, resulting in approximately 80% reduction in tumor volume of treated mice. Tumor growth inhibition was accompanied by L. casei-driven up-regulation of the TNF-related apoptosis-inducing ligand TRAIL and down-regulation of Survivin. Taken together, these findings provide evidence for beneficial tumor-inhibitory, anti-proliferative and pro-apoptotic effects driven by this probiotic LAB strain. PMID:26849051

Lactobacillus casei Exerts Anti-Proliferative Effects Accompanied by Apoptotic Cell Death and Up-Regulation of TRAIL in Colon Carcinoma Cells.

Directory of Open Access Journals (Sweden)

Angeliki Tiptiri-Kourpeti

Full Text Available Probiotic microorganisms such as lactic acid bacteria (LAB exert a number of strain-specific health-promoting activities attributed to their immunomodulatory, anti-inflammatory and anti-carcinogenic properties. Despite recent attention, our understanding of the biological processes involved in the beneficial effects of LAB strains is still limited. To this end, the present study investigated the growth-inhibitory effects of Lactobacillus casei ATCC 393 against experimental colon cancer. Administration of live Lactobacillus casei (as well as bacterial components thereof on murine (CT26 and human (HT29 colon carcinoma cell lines raised a significant concentration- and time-dependent anti-proliferative effect, determined by cell viability assays. Specifically, a dramatic decrease in viability of colon cancer cells co-incubated with 10(9 CFU/mL L. casei for 24 hours was detected (78% for HT29 and 52% for CT26 cells. In addition, live L. casei induced apoptotic cell death in both cell lines as revealed by annexin V and propidium iodide staining. The significance of the in vitro anti-proliferative effects was further confirmed in an experimental tumor model. Oral daily administration of 10(9 CFU live L. casei for 13 days significantly inhibited in vivo growth of colon carcinoma cells, resulting in approximately 80% reduction in tumor volume of treated mice. Tumor growth inhibition was accompanied by L. casei-driven up-regulation of the TNF-related apoptosis-inducing ligand TRAIL and down-regulation of Survivin. Taken together, these findings provide evidence for beneficial tumor-inhibitory, anti-proliferative and pro-apoptotic effects driven by this probiotic LAB strain.

Lactobacillus casei Exerts Anti-Proliferative Effects Accompanied by Apoptotic Cell Death and Up-Regulation of TRAIL in Colon Carcinoma Cells.

Science.gov (United States)

Tiptiri-Kourpeti, Angeliki; Spyridopoulou, Katerina; Santarmaki, Valentina; Aindelis, Georgios; Tompoulidou, Evgenia; Lamprianidou, Eleftheria E; Saxami, Georgia; Ypsilantis, Petros; Lampri, Evangeli S; Simopoulos, Constantinos; Kotsianidis, Ioannis; Galanis, Alex; Kourkoutas, Yiannis; Dimitrellou, Dimitra; Chlichlia, Katerina

2016-01-01

Probiotic microorganisms such as lactic acid bacteria (LAB) exert a number of strain-specific health-promoting activities attributed to their immunomodulatory, anti-inflammatory and anti-carcinogenic properties. Despite recent attention, our understanding of the biological processes involved in the beneficial effects of LAB strains is still limited. To this end, the present study investigated the growth-inhibitory effects of Lactobacillus casei ATCC 393 against experimental colon cancer. Administration of live Lactobacillus casei (as well as bacterial components thereof) on murine (CT26) and human (HT29) colon carcinoma cell lines raised a significant concentration- and time-dependent anti-proliferative effect, determined by cell viability assays. Specifically, a dramatic decrease in viability of colon cancer cells co-incubated with 10(9) CFU/mL L. casei for 24 hours was detected (78% for HT29 and 52% for CT26 cells). In addition, live L. casei induced apoptotic cell death in both cell lines as revealed by annexin V and propidium iodide staining. The significance of the in vitro anti-proliferative effects was further confirmed in an experimental tumor model. Oral daily administration of 10(9) CFU live L. casei for 13 days significantly inhibited in vivo growth of colon carcinoma cells, resulting in approximately 80% reduction in tumor volume of treated mice. Tumor growth inhibition was accompanied by L. casei-driven up-regulation of the TNF-related apoptosis-inducing ligand TRAIL and down-regulation of Survivin. Taken together, these findings provide evidence for beneficial tumor-inhibitory, anti-proliferative and pro-apoptotic effects driven by this probiotic LAB strain.

[The effect of prison crowding on prisoners' violence in Japan: testing with cointegration regressions and error correction models].

Science.gov (United States)

Yuma, Yoshikazu

2010-08-01

This research examined the effect of prison population densities (PPD) on inmate-inmate prison violence rates (PVR) in Japan using one-year-interval time-series data (1972-2006). Cointegration regressions revealed a long-run equilibrium relationship between PPD and PVR. PPD had a significant and increasing effect on PVR in the long-term. Error correction models showed that in the short-term, the effect of PPD was significant and positive on PVR, even after controlling for the effects of the proportions of males, age younger than 30 years, less than one-year incarceration, and prisoner/staff ratio. The results were discussed in regard to (a) differences between Japanese prisons and prisons in the United States, and (b) methodological problems found in previous research.

Analysis and Enhancements of a Prolific Macroscopic Model of Epilepsy

Directory of Open Access Journals (Sweden)

Christopher Fietkiewicz

2016-01-01

Full Text Available Macroscopic models of epilepsy can deliver surprisingly realistic EEG simulations. In the present study, a prolific series of models is evaluated with regard to theoretical and computational concerns, and enhancements are developed. Specifically, we analyze three aspects of the models: (1 Using dynamical systems analysis, we demonstrate and explain the presence of direct current potentials in the simulated EEG that were previously undocumented. (2 We explain how the system was not ideally formulated for numerical integration of stochastic differential equations. A reformulated system is developed to support proper methodology. (3 We explain an unreported contradiction in the published model specification regarding the use of a mathematical reduction method. We then use the method to reduce the number of equations and further improve the computational efficiency. The intent of our critique is to enhance the evolution of macroscopic modeling of epilepsy and assist others who wish to explore this exciting class of models further.

Coordination Skills during Vitrectomy in Treatment of Proliferative Diabetic Retinopathy

Institute of Scientific and Technical Information of China (English)

Xuehong Chen; Shanshan Luo; Yanchan Liu

2014-01-01

Purpose:.To discuss effective nursing and coordination skills for vitrectomy in the treatment of diabetic retinopathy. Methods: Fifty patients (51 eyes) with diabetic retinopathy required vitrectomy were enrolled in this study..Individual nursing service was delivered by strengthening preoperative preparation, providing psychological nursing, and intraopera-tive observation of the severity of diseases by circulating nurses;meticulous nursing was given postoperatively. Results:All 50 patients underwent surgery successfully..Intra-operatively,.patients had stable physical signs..Five patients had postoperative visual acuity0.3..No complicated infection was seen. Conclusion: For patients diagnosed with proliferative diabetic retinopathy requiring vitrectomy,.full preparations should be made and psychological nursing should be delivered preopera-tively, the severity of diseases and clinical reactions should be closely observed intraoperatively,.and proper processing and nursing measures should be taken postoperatively,.which col-lectively enhance surgical success rate,.decrease surgical com-plications,.and attain favorable treatment efficacy.(Eye Science 2014; 29:55-58).

Pulmonary Hypertension After Heart Transplantation in Patients Bridged with the Total Artificial Heart.

Science.gov (United States)

Shah, Rachit; Patel, Dhavalkumar B; Mankad, Anit K; Rennyson, Stephen L; Tang, Daniel G; Quader, Mohammed A; Smallfield, Melissa C; Kasirajan, Vigneshwar; Shah, Keyur B

2016-01-01

Pulmonary hypertension (PH) among heart transplant recipients is associated with an increased risk of mortality. Pulmonary hemodynamics improves after left ventricular assist device (LVAD) implantation; however, the impact of PH before total artificial heart (TAH) implantation on posttransplant hemodynamics and survival is unknown. This is a single center retrospective study aimed to evaluate the impact of TAH implantation on posttransplant hemodynamics and mortality in two groups stratified according to severity of PH: high (≥3 Woods units [WU]) and low (heart catheterization performed at baseline (before TAH) and posttransplant at 1 and 12 months. Patients in the high PVR group (n = 12) experienced improvement in PVR (baseline = 4.31 ± 0.7; 1-month = 1.69 ± 0.7, p heart transplantation (HT), but remained elevated. There was no significant difference in survival between the two groups at 12 months follow-up. Patients with high PVR who are bridged to transplant with TAH had improvement in PVR at 12 months after transplant, and the degree of PVR did not impact posttransplant survival.

Outcome after surgical treatment of chronic thromboembolic pulmonary hypertension: dealing with different patient subsets. A single-centre experience.

Science.gov (United States)

Nierlich, Patrick; Hold, Alina; Ristl, Robin

2016-11-01

Pulmonary endarterectomy (PEA) is the only curative treatment for patients suffering from chronic thromboembolic pulmonary hypertension (CTEPH). In patients with a pulmonary vascular resistance (PVR) higher than 1000 dynes s cm -5 , this procedure is linked with an increased perioperative risk. We compare the outcomes of patients with moderate to severe versus extremely elevated PVR. Between 1992 and 2013, 214 patients underwent PEA for CTEPH at our institution. All patient data were entered in a prospective database. We performed a retrospective analysis of our total patient collective and of subgroups defined by: PVR ≤ 800, PVR > 800 heart failure (n = 7) and multiorgan failure (n = 3). Bleeding, stroke, sepsis and pneumonia led to death in 1 patient each. Mortality was significantly higher in the two groups with PVR > 800, but absolute pressure reduction was also higher in these groups. The 1-year survival rate was 91.2%. Despite the increased perioperative risk and mortality, PEA should not be denied to patients with extremely elevated PVR but clear indication for surgery. Keeping increased perioperative risk and mortality in mind, significant pressure reduction and improved functional outcome can be achieved in the majority of these patients. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Synthesis, characterization and anti-proliferative activity of heterocyclic hypervalent organoantimony compounds.

Science.gov (United States)

Chen, Yi; Yu, Kun; Tan, Nian-Yuan; Qiu, Ren-Hua; Liu, Wei; Luo, Ning-Lin; Tong, Le; Au, Chak-Tong; Luo, Zi-Qiang; Yin, Shuang-Feng

2014-05-22

Three heterocyclic hypervalent organoantimony chlorides RN(CH2C6H4)2SbCl (2a R = t-Bu, 2b R = Cy, 2c R = Ph) and their chalcogenide derivatives [RN(CH2C6H4)2Sb]2O (3a R = t-Bu, 3b R = Cy, 3c R = Ph) were synthesized and characterized by techniques such as (1)H NMR, (13)C NMR, X-ray diffraction, and elemental analysis. It is found that the anti-proliferative activity detected over these compounds can be attributed to the coordination bond between the antimony and nitrogen atoms of these compounds. Moreover, a preliminary study on mechanistic action suggests that the inhibition effect is ascribable to cell cycle arrest and cell apoptosis. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Post-voiding residual urine and capacity increase in orthotopic urinary diversion: Standard vs modified technique

Directory of Open Access Journals (Sweden)

Bančević Vladimir

2010-01-01

Full Text Available Background/Aim. Ever since the time when the first orthotopic urinary diversion (pouch was performed there has been a constant improvement and modification of surgical techniques. The aim has been to create a urinary reservoir similar to normal bladder, to decrease incidence of postoperative complications and provide an improved life quality. The aim of this study was to compare postvoiding residual urine (PVR and capacity of the pouch constructed by standard or modified technique. Methods. In this prospective and partially retrospective clinical study we included 79 patients. In the group of 41 patients (group ST pouch was constructed using 50-70 cm of the ileum (standard technique. In the group of 38 patients (group MT pouch was constructed using 25-35 cm of the ileum (modified technique. Postoperatively, PVR and pouch capacity were measured using ultrasound in a 3-, 6- and 12-month period. Results. Postoperatively, an increase in PVR and pouch capacity was noticed in both groups. Twelve months postoperatively, PVR was significantly smaller in the group MT than in the group ST [23 (0-90 mL vs 109 (0-570 mL, p < 0,001]. In the same period the pouch capacity was significantly smaller in the MT group than in the ST group [460 (290-710 mL vs 892 (480-2 050 mL, p < 0.001]. Conclusion. Postoperatively, an increase in PVR and pouch capacity was noticed during a 12-month period. A year following the operation the pouch created from a shorter ileal segment reached capacity of the 'normal' bladder with small PVR. The pouch created by standard technique developed an unnecessary large PVR and capacity.

Compositions and methods involving methyladenosine phosphorylase in the diagnosis and treatment of proliferative disorders

Science.gov (United States)

Olopade, Olufunmilayo I.

2007-03-20

Disclosed are novel nucleic acid and peptide compositions comprising methylthioadenosine phosphorylase (MTAP) and methods of use for MTAP amino acid sequences and DNA segments comprising MTAP in the diagnosis of human cancers and development of MTAP-specific antibodies. Also disclosed are methods for the diagnosis and treatment of tumors and other proliferative cell disorders, and identification of tumor suppressor genes and gene products from the human 9p21-p22 chromosome region. Such methods are useful in the diagnosis of multiple tumor types such as bladder cancer, lung cancer, breast cancer, pancreatic cancer, brain tumors, lymphomas, gliomas, melanomas, and leukemias.

Structural and functional development of rat and mouse gastric mucous cells in relation to their proliferative activity

International Nuclear Information System (INIS)

Wattel, W.

1978-01-01

An investigation has been carried out to find a relation between the differentiation and the mitotic activity of gastric mucous cells of the rat and the mouse. It is shown that the bulk mucous production is carried out by the older, non-proliferative, surface mucous cells that line the foveolae and the gastric surface. One experiment describes the renewal of mouse gastric mucous cells following fast neutron irradiation. (C.F.)

Fibrinolysis and proliferative endarteritis: two related processes in chronic infections? The model of the blood-borne pathogen Dirofilaria immitis.

Directory of Open Access Journals (Sweden)

Javier González-Miguel

Full Text Available The interaction between blood-borne pathogens and fibrinolysis is one of the most important mechanisms that mediate invasion and the establishment of infectious agents in their hosts. However, overproduction of plasmin (final product of the route has been related in other contexts to proliferation and migration of the arterial wall cells and degradation of the extracellular matrix. We have recently identified fibrinolysis-activating antigens from Dirofilaria immitis, a blood-borne parasite whose key pathological event (proliferative endarteritis is produced by similar mechanisms to those indicated above. The objective of this work is to study how two of this antigens [actin (ACT and fructose-bisphosphate aldolase (FBAL] highly conserved in pathogens, activate fibrinolysis and to establish a relationship between this activation and the development of proliferative endarteritis during cardiopulmonary dirofilariasis. We demonstrate that both proteins bind plasminogen, enhance plasmin generation, stimulate the expression of the fibrinolytic activators tPA and uPA in endothelial cell cultures and are located on the surface of the worm in contact with the host's blood. ELISA, western blot and immunofluorescence techniques were employed for this purpose. Additionally, the implication of lysine residues in this interaction was analyzed by bioinformatics. The involvement of plasmin generated by the ACT/FBAL and plasminogen binding in cell proliferation and migration, and degradation of the extracellular matrix were shown in an "in vitro" model of endothelial and smooth muscle cells in culture. The obtained results indicate that ACT and FBAL from D. immitis activate fibrinolysis, which could be used by the parasite like a survival mechanism to avoid the clot formation. However, long-term overproduction of plasmin can trigger pathological events similar to those described in the emergence of proliferative endarteritis. Due to the high degree of

A Transgenic Mouse Model of Poliomyelitis.

Science.gov (United States)

Koike, Satoshi; Nagata, Noriyo

2016-01-01

Transgenic mice (tg mice) that express the human poliovirus receptor (PVR), CD155, are susceptible to poliovirus and develop a neurological disease that resembles human poliomyelitis. Assessment of the neurovirulence levels of poliovirus strains, including mutant viruses produced by reverse genetics, circulating vaccine-derived poliovirus, and vaccine candidates, is useful for basic research of poliovirus pathogenicity, the surveillance of circulating polioviruses, and the quality control of oral live poliovirus vaccines, and does not require the use of monkeys. Furthermore, PVR-tg mice are useful for studying poliovirus tissue tropism and host immune responses. PVR-tg mice can be bred with mice deficient in the genes involved in viral pathogenicity. This report describes the methods used to analyze the pathogenicity and immune responses of poliovirus using the PVR-tg mouse model.

High fructose-mediated attenuation of insulin receptor signaling does not affect PDGF-induced proliferative signaling in vascular smooth muscle cells.

Science.gov (United States)

Osman, Islam; Poulose, Ninu; Ganapathy, Vadivel; Segar, Lakshman

2016-11-15

Insulin resistance is associated with accelerated atherosclerosis. Although high fructose is known to induce insulin resistance, it remains unclear as to how fructose regulates insulin receptor signaling and proliferative phenotype in vascular smooth muscle cells (VSMCs), which play a major role in atherosclerosis. Using human aortic VSMCs, we investigated the effects of high fructose treatment on insulin receptor substrate-1 (IRS-1) serine phosphorylation, insulin versus platelet-derived growth factor (PDGF)-induced phosphorylation of Akt, S6 ribosomal protein, and extracellular signal-regulated kinase (ERK), and cell cycle proteins. In comparison with PDGF (a potent mitogen), neither fructose nor insulin enhanced VSMC proliferation and cyclin D1 expression. d-[ 14 C(U)]fructose uptake studies revealed a progressive increase in fructose uptake in a time-dependent manner. Concentration-dependent studies with high fructose (5-25mM) showed marked increases in IRS-1 serine phosphorylation, a key adapter protein in insulin receptor signaling. Accordingly, high fructose treatment led to significant diminutions in insulin-induced phosphorylation of downstream signaling components including Akt and S6. In addition, high fructose significantly diminished insulin-induced ERK phosphorylation. Nevertheless, high fructose did not affect PDGF-induced key proliferative signaling events including phosphorylation of Akt, S6, and ERK and expression of cyclin D1 protein. Together, high fructose dysregulates IRS-1 phosphorylation state and proximal insulin receptor signaling in VSMCs, but does not affect PDGF-induced proliferative signaling. These findings suggest that systemic insulin resistance rather than VSMC-specific dysregulation of insulin receptor signaling by high fructose may play a major role in enhancing atherosclerosis and neointimal hyperplasia. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of a novel enzyme-linked immunosorbent assay for serological diagnosis of porcine proliferative enteropathy

DEFF Research Database (Denmark)

Boesen, Henriette Toft; Jensen, Tim Kåre; Møller, Kristian

2005-01-01

was a specific and sensitive method for detecting specific antibodies, and may be a good alternative to the existing serological tests for L intracellularis. It may be usable for diagnosis of proliferative enteropathy and for determination of a herd's epidemiologic status....... experimentally infected pigs and 62 serum samples from naturally infected pigs the sensitivity of the ELISA was calculated to 98.0%. The specificity of the test was 99.3%, calculated on the basis of 273 serum samples collected in six herds free of L. intracellularis after medicated eradication. The novel ELISA...

F-18-FDG positron emission tomography findings correlate pathological proliferative activity of oral squamous cell carcinoma

International Nuclear Information System (INIS)

Toyoizumi, Osamu; Oriuchi, Noboru; Miyakubo, Mitsuyuki

2010-01-01

It is still controversial whether fluorodeoxyglucose (FDG) uptake is correlated with cellular proliferation and prognosis of oral squamous cell carcinoma (OSC). In this study, we performed positron emission tomography (PET) study and immunohistochemical analysis to elucidate the relationship between FDG uptake and expression of cellular proliferative markers and pathological prognostic markers in patients with OSC. FDG PET and immunohistochemical staining have been carried out in sixteen patients with OSC. Tumor uptake of FDG was expressed with standardized uptake value (SUV). The expression of Ki-67, Topoisomerase IIα (Topo IIα), p53, and p63 in cancer cells was quantitatively assessed with positivity of the immunohistochemical staining. SUV was compared with the results of immunohistochemical analysis. FDG PET study revealed that SUV ranged from 3.6 to 22.1 with average of 10.4. Average positive rate of Ki-67, Topo IIα, p53, and p63 was 68.9%, 58.9%, 72.0%, and 65.2%, respectively. Pearson product-moment correlation coefficient analysis revealed that SUV was significantly correlated with Ki-67 (r=0.616, p=0.01), Topo IIα (r=0.677, p=0.004), p53 (r=0.613, p=0.01), and p63 (r=0.710, p=0.002), respectively. The present preliminary study indicated that FDG uptake was closely correlated with pathological cellular proliferative and prognostic markers in patients with OSC. (author)

Cytosol cathepsin-D content and proliferative activity of human breast cancer. The Comitato Italiano per il Controllo di Qualita del Laboratorio in Oncologia.

Science.gov (United States)

Paradiso, A; Mangia, A; Correale, M; Abbate, I; Ferri, G; Piffanelli, A; Catozzi, L; Amadori, D; Riccobon, A; De Lena, M

1992-01-01

Mitogenic properties have been demonstrated in vitro for the lysosomal acidic protease cathepsin-D (cath-D). We investigated possible relationships between cath-D cytosol cell content and tumor proliferative activity in a series of 129 operable breast cancer patients. For total cytosol cath-D evaluation, a solid phase two-site immunoradiometric assay was utilized on tumor cell cytosol obtained for hormone receptor assay (DCC method). The percentage of S-phase cells was analyzed by 3H-thymidine autoradiographic assay. Median 3H-thymidine Labeling Index (3H-Tdr-LI) of the series was 2.7%; median cath-D content resulted 57 pmol/mg of protein cytosol and was significantly higher in node-positive with respect to the node-negative subgroup (p < 0.03). When classified in low, intermediate or high tumor cath-D content and slow or fast proliferative activity (cut-off: median values of the series), no significant agreement was found between the two variables. Statistical analysis, however, showed that a significant inverse correlation existed in node positive tumors between cath-D and 3H-Tdr-LI values which was even more evident in N-positive high estrogen receptor-positive (ER+) cases (coefficient of correlation = 0.6828; p = 0.0001). Cytosol cath-D content cannot be generally proposed as a direct marker of proliferative activity for operable breast cancer.

Immunochemical expression of proliferative cell nuclear antigen in aging cultured astrocytes

Directory of Open Access Journals (Sweden)

M. C. Vanzani

2003-08-01

Full Text Available Cell differentiation degree and mitotic activity were sequentially assessed by immunoperoxidase labeling of glial fibrillary acidic protein (GFAP and proliferative cell nuclear antigen (PCNA, respectively, in rat brain cultured astrocytes maintained up to 60 days in vitro (DIV of first subculture, or weekly passaged until their 12th subculture. Cell count was performed through a 0.01 mm2 section reticule and morphometric analysis with a stereological grid. The number of double immunoreactive cells peaked by 2 DIV to achieve its lowest value at 60 DIV. At 24 hs of cell seeding of successive passages, such values peaked by the 6th subculture to gradually decrease thereafter. Increasing cell hypertrophy was found during the long-term first subculture but not after passaging. At the end of the observation period, doubly immunolabeled astrocytes were still recorded, thus evidencing retention of proliferative potential despite aging.El grado de diferenciación celular y la actividad mitótica fueron secuencialmente determinados mediante marcación por inmunoperoxidasa de la proteína gliofibrilar ácida (GFAP y del antígeno nuclear de proliferación celular (PCNA, respectivamente, en cultivos astrocitarios obtenidos de encéfalo de rata y mantenidos hasta 60 días in vitro (DIV de su primer subcultivo, o mediante pasajes semanales hasta el 12do subcultivo. El conteo celular se realizó mediante una retícula de 0.01-mm2 de sección y el análisis morfométrico con una grilla estereológica. El número de células doblemente inmunorreactivas alcanzó valores máximos a los 2 DIV para descender a los menores a los 60 DIV. A las 24 hs de sembrado celular de los sucesivos pasajes, esos valores ascendieron hacia el 6to subcultivo para luego declinar. En cuanto a la hipertrofia celular, se observó en todo el curso del primer subcultivo, pero no durante los posteriores pasajes. Al final del período de observación, todavía se continuaban detectando

Making Women the Subjects of the Abortion Debate: A Class Exercise that Moves beyond "Pro-Choice" and "Pro-Life"

Science.gov (United States)

Crawley, Sara L.; Willman, Rebecca K.; Clark, Leisa; Walsh, Clare

2009-01-01

In this article, the authors describe a classroom exercise designed to put women (and children and men) back at the center of the abortion debate, avoiding the standard rhetoric and engaging reflection on how everyone might find common political goals among the so-called pro-life and pro-choice sides. The exercise the authors offer in this article…

Hyper-activation of Notch3 amplifies the proliferative potential of rhabdomyosarcoma cells.

Directory of Open Access Journals (Sweden)

Maria De Salvo

Full Text Available Rhabdomyosarcoma (RMS is a pediatric myogenic-derived soft tissue sarcoma that includes two major histopathological subtypes: embryonal and alveolar. The majority of alveolar RMS expresses PAX3-FOXO1 fusion oncoprotein, associated with the worst prognosis. RMS cells show myogenic markers expression but are unable to terminally differentiate. The Notch signaling pathway is a master player during myogenesis, with Notch1 activation sustaining myoblast expansion and Notch3 activation inhibiting myoblast fusion and differentiation. Accordingly, Notch1 signaling is up-regulated and activated in embryonal RMS samples and supports the proliferation of tumor cells. However, it is unable to control their differentiation properties. We previously reported that Notch3 is activated in RMS cell lines, of both alveolar and embryonal subtype, and acts by inhibiting differentiation. Moreover, Notch3 depletion reduces PAX3-FOXO1 alveolar RMS tumor growth in vivo. However, whether Notch3 activation also sustains the proliferation of RMS cells remained unclear. To address this question, we forced the expression of the activated form of Notch3, Notch3IC, in the RH30 and RH41 PAX3-FOXO1-positive alveolar and in the RD embryonal RMS cell lines and studied the proliferation of these cells. We show that, in all three cell lines tested, Notch3IC over-expression stimulates in vitro cell proliferation and prevents the effects of pharmacological Notch inhibition. Furthermore, Notch3IC further increases RH30 cell growth in vivo. Interestingly, knockdown of Notch canonical ligands JAG1 or DLL1 in RMS cell lines decreases Notch3 activity and reduces cell proliferation. Finally, the expression of Notch3IC and its target gene HES1 correlates with that of the proliferative marker Ki67 in a small cohort of primary PAX-FOXO1 alveolar RMS samples. These results strongly suggest that high levels of Notch3 activation increase the proliferative potential of RMS cells.

Peripheral blood T cell proliferative response to chlamydial organisms in gonococcal and non-gonococcal urethritis and presumed pelvic inflammatory disease

Science.gov (United States)

Shahmanesh, M.; Brunst, M.; Sukthankar, A.; Pearce, J. H.; Gaston, J. S.

1999-01-01

OBJECTIVE: To study peripheral blood mononuclear cell (PBMC) proliferative response to Chlamydia trachomatis elementary bodies in (a) controls, (b) various stages of gonococcal (c) and non-gonococcal urethritis, and (d) women with a clinical diagnosis of pelvic inflammatory disease (PID). METHODS: We categorised 102 men presenting to a GUM clinic with urethritis by organisms (C trachomatis (CT) or Neisseria gonorrhoeae (NG) (both by culture), and whether it was their first (urethritis naive) or subsequent (urethritis experienced) attack. 23 women presenting to the clinic with a clinical diagnosis of PID were also investigated. We measured PBMC proliferative responses to C trachomatis (DK20--an oculogenital strain, serovar E), lysate of McCoy cells (used to propagate chlamydiae), and the recall antigen PPD. Controls were 37 men and women without present or past history of urethritis or chlamydial infection. Results were expressed as the ratio of the stimulation index (SI) obtained with DK20 compared with McCoy cells (DK index), and the ratio of the SI obtained with DK20 compared with PPD (PPD index). RESULTS: The median SI to DK20 in the urethritis was 12.7 which was significantly higher than the controls (7.6, p urethritis patients (17.4) and the controls (22.4). All urethritis patient subgroups had a significantly higher DK index and PPD index than the controls. There was no difference in the PPD and DK index between urethritis naive and urethritis experienced patients and between the culture positive and culture negative urethritis subgroups. In PID patients only the PPD index was significantly higher than the controls. CONCLUSION: Men presenting with urethritis and women presenting with PID both have significantly greater peripheral blood mononuclear cell proliferative responses to the DK20 strain of C trachomatis than controls. A similar T cell proliferative response pattern in urethritis naive patients with either gonococcal or non-gonococcal urethritis could

Eco-friendly synthesis, in vitro anti-proliferative evaluation, and 3D-QSAR analysis of a novel series of monocationic 2-aryl/heteroaryl-substituted 6-(2-imidazolinyl)benzothiazole mesylates.

Science.gov (United States)

Racané, Livio; Ptiček, Lucija; Sedić, Mirela; Grbčić, Petra; Kraljević Pavelić, Sandra; Bertoša, Branimir; Sović, Irena; Karminski-Zamola, Grace

2018-04-17

Herein, we describe the synthesis of twenty-one novel water-soluble monocationic 2-aryl/heteroaryl-substituted 6-(2-imidazolinyl)benzothiazole mesylates 3a-3u and present the results of their anti-proliferative assays. Efficient syntheses were achieved by three complementary simple two-step synthetic protocols based on the condensation reaction of aryl/heteroaryl carbaldehydes or carboxylic acid. We developed an eco-friendly synthetic protocol using glycerol as green solvent, particularly appropriate for the condensation of thermally and acid-sensitive heterocycles such as furan, benzofuran, pyrrole, and indole. Screening of anti-proliferative activity was performed on four human tumour cell lines in vitro including pancreatic cancer (CFPAC-1), metastatic colon cancer (SW620), hepatocellular carcinoma (HepG2), and cervical cancer (HeLa), as well as in normal human fibroblast cell lines. All tested compounds showed strong to moderate anti-proliferative activity on tested cell lines depending on the structure containing aryl/heteroaryl moiety coupled to 6-(2-imidazolinyl)benzothiazole moiety. The most potent cytostatic effects on all tested cell lines with [Formula: see text] values ranging from 0.1 to 3.70 [Formula: see text] were observed for benzothiazoles substituted with naphthalene-2-yl 3c, benzofuran-2-yl 3e, indole-3-yl 3j, indole-2-yl 3k, quinoline-2-yl 3s, and quinoline-3-yl 3t and derivatives substituted with phenyl 3a, naphthalene-1-yl 3b, benzothiazole-2-yl 3g, benzothiazole-6-yl 3h, N-methylindole-3-yl 3l, benzimidazole-2-yl 3n, benzimidazole-5(6)-yl 3o, and quinolone-4-yl 3u with [Formula: see text] values ranging from 1.1 to 29.1 [Formula: see text]. Based on obtained anti-proliferative activities, 3D-QSAR models for five cell lines were derived. Molecular volume, molecular surface, the sum of hydrophobic surface areas, molecular mass, and possibility of making dispersion forces were identified by QSAR analyses as molecular properties that are

The truncated splice variant of peroxisome proliferator-activated receptor alpha, PPARα-tr, autonomously regulates proliferative and pro-inflammatory genes

International Nuclear Information System (INIS)

Thomas, Maria; Bayha, Christine; Klein, Kathrin; Müller, Simon; Weiss, Thomas S.; Schwab, Matthias; Zanger, Ulrich M.

2015-01-01

The peroxisome proliferator-activated receptor alpha (PPARα) controls lipid/energy homeostasis and inflammatory responses. The truncated splice variant PPARα-tr was suggested to exert a dominant negative function despite being unable to bind consensus PPARα DNA response elements. The distribution and variability factor of each PPARα variant were assessed in the well-characterized cohort of human liver samples (N = 150) on the mRNA and protein levels. Specific siRNA-mediated downregulation of each transcript as well as specific overexpression with subsequent qRT-PCR analysis of downstream genes was used for investigation of specific functional roles of PPARα-wt and PPARα-tr forms in primary human hepatocytes. Bioinformatic analyses of genome-wide liver expression profiling data suggested a possible role of PPARα-tr in downregulating proliferative and pro-inflammatory genes. Specific gene silencing of both forms in primary human hepatocytes showed that induction of metabolic PPARα-target genes by agonist WY14,643 was prevented by PPARα-wt knock-down but neither prevented nor augmented by PPARα-tr knock-down. WY14,643 treatment did not induce proliferative genes including MYC, CDK1, and PCNA, and knock-down of PPARα-wt had no effect, while PPARα-tr knock-down caused up to 3-fold induction of these genes. Similarly, induction of pro-inflammatory genes IL1B, PTGS2, and CCL2 by IL-6 was augmented by knock-down of PPARα-tr but not of PPARα-wt. In contrast to human proliferative genes, orthologous mouse genes were readily inducible by WY14,643 in PPARα-tr non-expressing AML12 mouse hepatocytes. Induction was augmented by overexpression of PPARα-wt and attenuated by overexpression of PPARα-tr. Pro-inflammatory genes including IL-1β, CCL2 and TNFα were induced by WY14,643 in mouse and human cells and both PPARα forms attenuated induction. As potential mechanism of PPARα-tr inhibitory action we suggest crosstalk with WNT/β-catenin pathway. Finally

Cranberry and Grape Seed Extracts Inhibit the Proliferative Phenotype of Oral Squamous Cell Carcinomas

Directory of Open Access Journals (Sweden)

Kourt Chatelain

2011-01-01

Full Text Available Proanthocyanidins, compounds highly concentrated in dietary fruits, such as cranberries and grapes, demonstrate significant cancer prevention potential against many types of cancer. The objective of this study was to evaluate cranberry and grape seed extracts to quantitate and compare their anti-proliferative effects on the most common type of oral cancer, oral squamous cell carcinoma. Using two well-characterized oral squamous cell carcinoma cell lines, CAL27 and SCC25, assays were performed to evaluate the effects of cranberry and grape seed extract on phenotypic behaviors of these oral cancers. The proliferation of both oral cancer cell lines was significantly inhibited by the administration of cranberry and grape seed extracts, in a dose-dependent manner. In addition, key regulators of apoptosis, caspase-2 and caspase-8, were concomitantly up-regulated by these treatments. However, cranberry and grape seed extracts elicited differential effects on cell adhesion, cell morphology, and cell cycle regulatory pathways. This study represents one of the first comparative investigations of cranberry and grape seed extracts and their anti-proliferative effects on oral cancers. Previous findings using purified proanthocyanidin from grape seed extract demonstrated more prominent growth inhibition, as well as apoptosis-inducing, properties on CAL27 cells. These observations provide evidence that cranberry and grape seed extracts not only inhibit oral cancer proliferation but also that the mechanism of this inhibition may function by triggering key apoptotic regulators in these cell lines. This information will be of benefit to researchers interested in elucidating which dietary components are central to mechanisms involved in the mediation of oral carcinogenesis and progression.

Alteration of melatonin secretion in patients with type 2 diabetes and proliferative diabetic retinopathy

Directory of Open Access Journals (Sweden)

Hikichi T

2011-05-01

Full Text Available Taiichi Hikichi1, Naohiro Tateda2, Toshiaki Miura31Department of Ophthalmology, Ohtsuka Eye Hospital, Sapporo; 2Asahikawa National College of Technology, Asahikawa; 3Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, JapanBackground: The purpose of this study was to evaluate the dynamics of plasma melatonin secretion in patients with type 2 diabetes mellitus and diabetic retinopathy.Methods: Plasma melatonin levels were measured by high-performance liquid chromatography in 56 patients. Patients were divided into a diabetic group (30 patients and a nondiabetic group (26 patients. The diabetic group was divided further into a proliferative diabetic retinopathy (PDR group (n = 14 and a nonproliferative diabetic retinopathy (NPDR group (n = 16. Plasma melatonin levels obtained at midnight and 3 am were compared between the groups.Results: Nighttime melatonin levels were significantly lower in the diabetic group than in the nondiabetic group (P < 0.03 and lower in the PDR group than in the nondiabetic and NPDR groups (P < 0.01 and P < 0.03, respectively, but no significant difference was found between the nondiabetic and NPDR groups. The daytime melatonin level did not significantly differ between the nondiabetic and diabetic groups or between the nondiabetic, NPDR, and PDR groups.Conclusion: The nighttime melatonin level is altered in patients with diabetes and PDR but not in diabetic patients without PDR. Although patients with PDR may have various dysfunctions that affect melatonin secretion more severely, advanced dysfunction of retinal light perception may cause altered melatonin secretion. Alteration of melatonin secretion may accelerate further occurrence of complications in diabetic patients.Keywords: circadian rhythm, diabetes, proliferative diabetic retinopathy, melatonin

The utility of a Personal Values Report for medical decision-making.

Science.gov (United States)

Henderson, W; Corke, C

2015-09-01

Our aim was to determine if a patient's Personal Values Report (PVR) has a positive impact on a doctor's decisions regarding treatment. We conducted a prospective cohort study delivering a short, web-based hypothetical case-centred questionnaire to intensive care doctors practising in Australia and New Zealand. One hundred and twenty-four intensive care consultants and registrars agreed to participate in an online questionnaire in two routine mailings between November 2013 and February 2014. We evaluated the effect of a PVR on clinical decision-making in a case-based scenario. In addition, participants rated the utility of the PVR on their decision-making process. Participants were presented with a difficult scenario in a frail elderly man where death was almost inevitable without aggressive support but survival with severe disability was possible with significant intervention. Most doctors (52.4%) elected to continue ventilation and admit to ICU. After the PVR was made available, only 8.1% of doctors continued to choose to admit the patient to the ICU. In all cases where admission to the ICU was chosen after seeing the PVR, the admission to the ICU was stated to be to permit family to arrive before withdrawing support (an approach which was consistent with the values stated in the PVR). One hundred and twenty-one of the 124 participants (97.6%) agreed or strongly agreed that the PVR helped them get an understanding of the patient's wishes, whereas none of the participants (0%) were unsure, disagreed or strongly disagreed with this statement. The remaining 2.4% did not answer the question. It is surmised that PVRs pre-written by patients are potentially an effective and valuable tool for use in helping doctors make decisions regarding patient care.

Clinical Implications of Residual Urine in Korean Benign Prostatic Hyperplasia (BPH) Patients: A Prognostic Factor for BPH-Related Clinical Events.

Science.gov (United States)

Ko, Young Hwii; Chae, Ji Yun; Jeong, Seung Min; Kang, Jae Il; Ahn, Hong Jae; Kim, Hyung Woo; Kang, Sung Gu; Jang, Hoon Ah; Cheon, Jun; Kim, Je Jong; Lee, Jeong Gu

2010-12-01

Although post-void residual urine (PVR) is frequently utilized clinically in patients with benign prostatic hyperplasia (BPH), mainly because of its procedural simplicity, its role as a clinical prognostic factor, predictive of treatment goals, is still under much dispute. We investigated the predictive value of PVR for BPH-related clinical events including surgery, acute urinary retention (AUR), and admission following urinary tract infection (UTI). From January to June of 2006, patients over 50 years of age who were diagnosed with BPH for the first time at the outpatient clinic and were then treated for at least 3 years with medications were enrolled in this study. The variables of patients who underwent surgical intervention for BPH, had occurrences of AUR, or required admission due to UTI (Group 1, n=43) were compared with those of patients who were maintained with medications only (Group 2, n=266). Group 1 had a significantly higher PVR, more severe symptoms, and a larger prostate at the time of the initial diagnosis in both the univariate and the multivariate analysis. In the 39 patients who underwent BPH-related surgery, although there was a significant change in Qmax at the time of surgery (mean, 13.1 months), PVR and the symptom score remained unchanged compared with the initial evaluation. In the receiver-operating characteristic curve analysis, the area under the curve of Group 1 was in the order of prostate volume (0.834), PVR (0.712), and symptom score (0.621). When redivided by arbitrarily selected PVR cutoffs of 50 mL, 100 mL, and 150 mL, the relative risk of clinical BPH progression was measured as 3.93, 2.61, and 2.11. These data indicate that, in the symptomatic Korean population, increased PVR at baseline is a significant indicator of BPH-related clinical events along with increased symptom score or prostate volume.

Lack of relationship between an insertion/deletion polymorphism in the angiotensin I-converting enzyme gene and diabetic nephropathy and proliferative retinopathy in IDDM patients

DEFF Research Database (Denmark)

Tarnow, L; Cambien, Francois; Rossing, P

1995-01-01

Genotypic abnormalities of the renin-angiotensin system have been suggested as a risk factor for the development of diabetic nephropathy and proliferative retinopathy. We studied the relationship between an insertion(I)/deletion (D) polymorphism in the angiotensin-converting enzyme (ACE) gene...... (40%) had proliferative retinopathy, and 67 patients (17%) had no diabetic retinopathy. There was no difference in genotype distribution between IDDM patients with diabetic nephropathy and those with normalbuminuria: 63 (32%)/95 (48%)/40 (20%) vs. 67 (35%)/77 (41%)/46 (24%) had DD/ID/II genotypes...... by ACE/ID polymorphism, mean arterial blood pressure, and glomerular filtration rate (r2 = 0.30, P retinopathy and those without diabetic retinopathy: 52 (34%)/74 (48%)/29 (19%) vs. 26 (39%)/25 (37...

Pulmonary vascular responses during acute and sustained respiratory alkalosis or acidosis in intact newborn piglets.

Science.gov (United States)

Gordon, J B; Rehorst-Paea, L A; Hoffman, G M; Nelin, L D

1999-12-01

Acute alkalosis-induced pulmonary vasodilation and acidosis-induced pulmonary vasoconstriction have been well described, but responses were generally measured within 5-30 min of changing pH. In contrast, several in vitro studies have found that relatively brief periods of sustained alkalosis can enhance, and sustained acidosis can decrease, vascular reactivity. In this study of intact newborn piglets, effects of acute (20 min) and sustained (60-80 min) alkalosis or acidosis on baseline (35% O2) and hypoxic (12% O2) pulmonary vascular resistance (PVR) were compared with control piglets exposed only to eucapnia. Acute alkalosis decreased hypoxic PVR, but sustained alkalosis failed to attenuate either baseline PVR or the subsequent hypoxic response. Acute acidosis did not significantly increase hypoxic PVR, but sustained acidosis markedly increased both baseline PVR and the subsequent hypoxic response. Baseline PVR was similar in all piglets after resumption of eucapnic ventilation, but the final hypoxic response was greater in piglets previously exposed to alkalosis than in controls. Thus, hypoxic pulmonary vasoconstriction was not attenuated during sustained alkalosis, but was accentuated during sustained acidosis and after the resumption of eucapnia in alkalosis-treated piglets. Although extrapolation of data from normal piglets to infants and children with pulmonary hypertension must be done with caution, this study suggests that sustained alkalosis may be of limited efficacy in treating acute hypoxia-induced pulmonary hypertension and the risks of pulmonary hypertension must be considered when using ventilator strategies resulting in permissive hypercapnic acidosis.

Dysregulation of T lymphocyte proliferative responses in autoimmunity.

Directory of Open Access Journals (Sweden)

Sydney K Elizer

Full Text Available T cells are critically dependent on cellular proliferation in order to carry out their effector functions. Autoimmune strains are commonly thought to have uncontrolled T cell proliferation; however, in the murine model of autoimmune diabetes, hypo-proliferation of T cells leading to defective AICD was previously uncovered. We now determine whether lupus prone murine strains are similarly hyporesponsive. Upon extensive characterization of T lymphocyte activation, we have observed a common feature of CD4 T cell activation shared among three autoimmune strains-NOD, MRL, and NZBxNZW F1s. When stimulated with a polyclonal mitogen, CD4 T cells demonstrate arrested cell division and diminished dose responsiveness as compared to the non-autoimmune strain C57BL/6, a phenotype we further traced to a reliance on B cell mediated costimulation, which underscores the success of B cell directed immune therapies in preventing T cell mediated tissue injury. In turn, the diminished proliferative capacity of these CD4 T cells lead to a decreased, but activation appropriate, susceptibility to activation induced cell death. A similar decrement in stimulation response was observed in the CD8 compartment of NOD mice; NOD CD8 T cells were distinguished from lupus prone strains by a diminished dose-responsiveness to anti-CD3 mediated stimulation. This distinction may explain the differential pathogenetic pathways activated in diabetes and lupus prone murine strains.

Rehabilitation effect of oral drug on the patients with proliferative diabetic retinopathy after operation

Directory of Open Access Journals (Sweden)

Wei Zu

2014-08-01

Full Text Available AIM:To observe the rehabilitation effect of oral Calcium Dobesilate Tablets and Epalrestat Tablets on the proliferative diabetic retinopathy(PDRpatients after vitrectomy.METHODS: After vitrectomy patients informed consent, they were randomly divided into intervention group and control group, and their vision and fundus were followed up and compared at 2d; 3, 6, 9, 12mo after operation.RESULTS: The recovery and sustainment of visual acuity, and subsiding of macular edema of patients in drug intervention group were significantly better than that in control group.CONCLUSION: PDR patients after vitrectomy actively orally take medicine to protect retina, which can improve vision and fundus rehabilitation.

Proliferative myositis of the latissimus dorsi presenting in a 20-year-old male athlete

LENUS (Irish Health Repository)

Mc Hugh, N

2017-08-01

We describe the case of a 20-year-old rower presenting with an uncommon condition of Proliferative Myositis (PM) affecting the Latissimus Dorsi (LD). PM is a rare, benign tumour infrequently developing in the upper back. Its rapid growth and firm consistency may mistake it for sarcoma at presentation. Therefore, careful multidisciplinary work-up is crucial, and should involve appropriate radiological and histopathological investigations. Here, we propose the aetiology of LD PM to be persistent myotrauma induced by repetitive rowing motions. Symptoms and rate of progression ultimately determine the management which includes surveillance and\\/or conservative resection. There have been no documented cases of recurrence or malignant transformation.

Immunohistochemical Estimates of Angiogenesis, Proliferative Activity, p53 Expression, and Multiple Drug Resistance Have No Prognostic Impact in Osteosarcoma: A Comparative Clinicopathological Investigation

DEFF Research Database (Denmark)

Sørensen, Flemming Brandt; Jensen, Kenneth; Vaeth, Michael

2008-01-01

Purpose. To investigate angiogenesis, multiple drug resistance (MDR) and proliferative activity as prognostic variables in patients suffering from osteosarcoma. Methods. Histologic biopsies from 117 patients treated in the period from 1972 through 1999 were immunohistologically investigated...

T-dependence of human B lymphocyte proliferative response to mitogens.

Science.gov (United States)

Brochier, J; Samarut, C; Gueho, J P; Revillard, J P

1976-01-01

Human peripheral blood and tonsil lymphocytes were fractionated on anti-Ig-coated Sephadex columns or by centrifugation after rosetting with native sheep erythrocytes. Both methods allowed the recovery of B and T-enriched populations the purity of which was checked by fluorescein-labelled anti-Ig serum, E and EAC rosette formation, and heterologous antisera specific for B or T lymphocytes. The proliferative response of T cells to PHA, Con A, PWM, and ALS was not found different from that of unfractionated cells, whereas no response of the B cells could be observed to these mitogens providing that no contaminating T cells were present. Addition of T lymphocytes to these unresponsive B cells allowed them to respond to phytomitogens, but not to ALS. X-irradiated T cells could, to some extent, replace the diving T lymphocytes; no T-replacing factor could be found in cell-free supernatants from T cells, whether or not they had been activated by mitrogens. This model of B-T cooperation appears useful for studying the differentiation and maturation of human B lymphocytes.

Anti-proliferative therapy for HIV cure: a compound interest approach.

Science.gov (United States)

Reeves, Daniel B; Duke, Elizabeth R; Hughes, Sean M; Prlic, Martin; Hladik, Florian; Schiffer, Joshua T

2017-06-21

In the era of antiretroviral therapy (ART), HIV-1 infection is no longer tantamount to early death. Yet the benefits of treatment are available only to those who can access, afford, and tolerate taking daily pills. True cure is challenged by HIV latency, the ability of chromosomally integrated virus to persist within memory CD4 + T cells in a non-replicative state and activate when ART is discontinued. Using a mathematical model of HIV dynamics, we demonstrate that treatment strategies offering modest but continual enhancement of reservoir clearance rates result in faster cure than abrupt, one-time reductions in reservoir size. We frame this concept in terms of compounding interest: small changes in interest rate drastically improve returns over time. On ART, latent cell proliferation rates are orders of magnitude larger than activation and new infection rates. Contingent on subtypes of cells that may make up the reservoir and their respective proliferation rates, our model predicts that coupling clinically available, anti-proliferative therapies with ART could result in functional cure within 2-10 years rather than several decades on ART alone.

Chemical composition, antioxidant, anti-inflammatory and anti-proliferative activities of essential oils of plants from Burkina Faso.

Directory of Open Access Journals (Sweden)

Bagora Bayala

Full Text Available This research highlights the chemical composition, antioxidant, anti-inflammatory and anti-proliferative activities of essential oils from leaves of Ocimum basilicum, Ocimum americanum, Hyptis spicigera, Lippia multiflora, Ageratum conyzoides, Eucalyptus camaldulensis and Zingiber officinale. Essential oils were analyzed by gas chromatography-mass spectrometry and gas chromatography-flame ionization detector. Major constituents were α-terpineol (59.78% and β-caryophyllene (10.54% for Ocimum basilicum; 1, 8-cineol (31.22%, camphor (12.730%, α-pinene (6.87% and trans α-bergamotene (5.32% for Ocimum americanum; β-caryophyllene (21%, α-pinene (20.11%, sabinene (10.26%, β-pinene (9.22% and α-phellandrene (7.03% for Hyptis spicigera; p-cymene (25.27%, β-caryophyllene (12.70%, thymol (11.88, γ-terpinene (9.17% and thymyle acetate (7.64% for Lippia multiflora; precocene (82.10%for Ageratum conyzoides; eucalyptol (59.55%, α-pinene (9.17% and limonene (8.76% for Eucalyptus camaldulensis; arcurcumene (16.67%, camphene (12.70%, zingiberene (8.40%, β-bisabolene (7.83% and β-sesquiphellandrène (5.34% for Zingiber officinale. Antioxidant activities were examined using 1,1-diphenyl-2-picryl-hydrazyl (DPPH and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS methods. O. basilicum and L. multiflora exhibited the highest antioxidant activity in DPPH and ABTS tests, respectively. Anti-inflammatory properties were evaluated by measuring the inhibition of lipoxygenase activity and essential oil of Z. officinale was the most active. Anti-proliferative effect was assayed by the measurement of MTT on LNCaP and PC-3 prostate cancer cell lines, and SF-763 and SF-767 glioblastoma cell lines. Essential oils from A. conyzoides and L. multiflora were the most active on LNCaP and PC-3 cell lines, respectively. The SF-767 glioblastoma cell line was the most sensitive to O. basilicum and L. multiflora EOs while essential oil of A. conyzoides showed the

A review of wave mechanics in the pulmonary artery with an emphasis on wave intensity analysis

DEFF Research Database (Denmark)

Su, Junjing; Hilberg, Ole; Howard, Luke

2016-01-01

Mean pulmonary arterial pressure and pulmonary vascular resistance (PVR) remain the most common haemodynamic measures to evaluate the severity and prognosis of pulmonary hypertension. However, PVR only captures the non-oscillatory component of the right ventricular hydraulic load and neglects...

Proliferative capacity of stem/progenitor-like cells in the kidney may associate with the outcome of patients with acute tubular necrosis.

Science.gov (United States)

Ye, Youxin; Wang, Bingyin; Jiang, Xinxin; Hu, Weiming; Feng, Jian; Li, Hua; Jin, Mei; Ying, Yingjuan; Wang, Wenjuan; Mao, Xiaoou; Jin, Kunlin

2011-08-01

Animal studies indicate that adult renal stem/progenitor cells can undergo rapid proliferation in response to renal injury, but whether the same is true in humans is largely unknown. To examine the profile of renal stem/progenitor cells responsible for acute tubular necrosis in human kidney, double and triple immunostaining was performed using proliferative marker and stem/progenitor protein markers on sections from 10 kidneys with acute tubular necrosis and 4 normal adult kidneys. The immunopositive cells were recorded using 2-photon confocal laser scanning microscopy. We found that dividing cells were present in the tubules of the cortex and medulla, as well as the glomerulus in normal human kidney. Proliferative cells in the parietal layer of Bowman capsule expressed CD133, and dividing cells in the tubules expressed immature cell protein markers paired box gene 2, vimentin, and nestin. After acute tubular necrosis, Ki67-positive cells in the cortex tubules significantly increased compared with normal adult kidney. These Ki67-positive cells expressed CD133 and paired box gene 2, but not the cell death marker, activated caspase-3. In addition, the number of dividing cells increased significantly in patients with acute tubular necrosis who subsequently recovered, compared with patients with acute tubular necrosis who consequently developed protracted acute tubular necrosis or died. Our data suggest that renal stem/progenitor cells may reside not only in the parietal layer of Bowman capsule but also in the cortex and medulla in normal human kidney, and the proliferative capacity of renal stem/progenitor cells after acute tubular necrosis may be an important determinant of a patient's outcome. Copyright © 2011 Elsevier Inc. All rights reserved.

Methylthioadenosine phosphorylase compositions and methods of use in the diagnosis and treatment of proliferative disorders

Science.gov (United States)

Olopade, Olufunmilayo I.

2005-03-22

Disclosed are novel nucleic acid and peptide compositions comprising methythlioadenosine phosphorylase (MTAP) and methods of use for MTAP amino acid sequences and DNA segments comprising MTAP in the diagnosis of human cancers and development of MTAP-specific antibodies. Also disclosed are methods for the diagnosis and treatment of tumors and other proliferative cell disorders, and idenification tumor suppressor genes and gene products from the human 9p21-p22 chromosome region. Such methods are useful in the diagnosis of multiple tumor types such as bladder cancer, lung cancer, breast cancer, pancreatic cancer, brain tumors, lymphomas, gliomas, melanomas, and leukemias.

Bilateral Proliferative Retinopathy as the Initial Presentation of Chronic Myeloid Leukemia

Science.gov (United States)

Macedo, Mafalda S. F.; Figueiredo, Ana R. M.; Ferreira, Natália N.; Barbosa, Irene M. A.; Furtado, Maria João F. B. S.; Correia, Nuno F. C. B. A.; Gomes, Miguel P.; Lume, Miguel R. B.; Menéres, Maria João S.; Santos, Marinho M. N.; Meireles S., M. Angelina C.

2013-01-01

The authors report a rare case of a 48-year-old male with chronic myeloid leukemia (CML) who initially presented with a bilateral proliferative retinopathy. The patient complained of recent visual loss and floaters in both eyes (BE). Ophthalmologic evaluation revealed a best corrected visual acuity (BCVA) of 20/50 in the right eye and 20/200 in the left eye (LE). Fundoscopy showed the presence of bilateral peripheral capillary dropout with multiple retinal sea fan neovascularisations, which were confirmed on fluorescein angiography. Full blood count revealed hyperleukocytosis, thrombocytosis, anemia, and hyperuricemia. Bone marrow aspiration and biopsy showed the reciprocal chromosomal translocation t (9;22), diagnostic of CML. The patient was started on hydroxyurea, allopurinol and imatinib mesylate. He received bilateral panretinal laser photocoagulation and a vitrectomy was performed in the LE. The patient has been in complete hematologic, cytogenetic, and major molecular remission while on imatinib and his BCVA is 20/25 in BE. PMID:24339689

A synthetic cryptochrome inhibitor induces anti-proliferative effects and increases chemosensitivity in human breast cancer cells

Energy Technology Data Exchange (ETDEWEB)

Chun, Sung Kook [Department of Brain & Cognitive Sciences, Daegu-Gyeongbuk Institute of Science & Technology, Daegu, 711-873 (Korea, Republic of); Department of Biological Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Department of Brain & Cognitive Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Chung, Sooyoung [Department of Biological Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Department of Biomedical Sciences, College of Medicine, Korea University, Seoul, 136-705 (Korea, Republic of); Kim, Hee-Dae [Department of Biological Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Lee, Ju Hyung [Department of Systems Biology, Yonsei University College of Life Science and Biotechnology, Seoul 120-749 (Korea, Republic of); Jang, Jaebong [College of Pharmacy, Seoul National University, Seoul, 151-742 (Korea, Republic of); Kim, Jeongah; Kim, Doyeon [Department of Brain & Cognitive Sciences, Daegu-Gyeongbuk Institute of Science & Technology, Daegu, 711-873 (Korea, Republic of); Department of Biological Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Department of Brain & Cognitive Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Son, Gi Hoon [Department of Biomedical Sciences, College of Medicine, Korea University, Seoul, 136-705 (Korea, Republic of); Oh, Young J. [Department of Systems Biology, Yonsei University College of Life Science and Biotechnology, Seoul 120-749 (Korea, Republic of); Suh, Young-Ger [College of Pharmacy, Seoul National University, Seoul, 151-742 (Korea, Republic of); Lee, Cheol Soon [Gachon Clinical Trials Center, Gachon University, Incheon, 417-842 (Korea, Republic of); and others

2015-11-13

Disruption of circadian rhythm is a major cause of breast cancer in humans. Cryptochrome (CRY), a circadian transcription factor, is a risk factor for initiation of breast cancer, and it is differentially expressed between normal and breast cancer tissues. Here, we evaluated the anti-proliferative and pro-apoptotic activity of KS15, a recently discovered small-molecule inhibitor of CRY, in human breast cancer cells. First, we investigated whether KS15 treatment could promote E-box-mediated transcription by inhibiting the activity of CRY in MCF-7 human breast cancer cells. Protein and mRNA levels of regulators of cell cycle and apoptosis, as well as core clock genes, were differentially modulated in response to KS15. Next, we investigated whether KS15 could inhibit proliferation and increase sensitivity to anti-tumor drugs in MCF-7 cells. We found that KS15 decreased the speed of cell growth and increased the chemosensitivity of MCF-7 cells to doxorubicin and tamoxifen, but had no effect on MCF-10A cells. These findings suggested that pharmacological inhibition of CRY by KS15 exerts an anti-proliferative effect and increases sensitivity to anti-tumor drugs in a specific type of breast cancer. - Highlights: • Cryptochrome inhibitor (KS15) has anti-tumor activity to human breast cancer cells. • KS15 induces differential changes in cell cycle regulators and pro-apoptotic genes. • KS15 inhibits MCF-7 cell growth and enhances susceptibility to anti-tumor drugs.

A synthetic cryptochrome inhibitor induces anti-proliferative effects and increases chemosensitivity in human breast cancer cells

International Nuclear Information System (INIS)

Chun, Sung Kook; Chung, Sooyoung; Kim, Hee-Dae; Lee, Ju Hyung; Jang, Jaebong; Kim, Jeongah; Kim, Doyeon; Son, Gi Hoon; Oh, Young J.; Suh, Young-Ger; Lee, Cheol Soon

2015-01-01

Disruption of circadian rhythm is a major cause of breast cancer in humans. Cryptochrome (CRY), a circadian transcription factor, is a risk factor for initiation of breast cancer, and it is differentially expressed between normal and breast cancer tissues. Here, we evaluated the anti-proliferative and pro-apoptotic activity of KS15, a recently discovered small-molecule inhibitor of CRY, in human breast cancer cells. First, we investigated whether KS15 treatment could promote E-box-mediated transcription by inhibiting the activity of CRY in MCF-7 human breast cancer cells. Protein and mRNA levels of regulators of cell cycle and apoptosis, as well as core clock genes, were differentially modulated in response to KS15. Next, we investigated whether KS15 could inhibit proliferation and increase sensitivity to anti-tumor drugs in MCF-7 cells. We found that KS15 decreased the speed of cell growth and increased the chemosensitivity of MCF-7 cells to doxorubicin and tamoxifen, but had no effect on MCF-10A cells. These findings suggested that pharmacological inhibition of CRY by KS15 exerts an anti-proliferative effect and increases sensitivity to anti-tumor drugs in a specific type of breast cancer. - Highlights: • Cryptochrome inhibitor (KS15) has anti-tumor activity to human breast cancer cells. • KS15 induces differential changes in cell cycle regulators and pro-apoptotic genes. • KS15 inhibits MCF-7 cell growth and enhances susceptibility to anti-tumor drugs.

Effect of Enterococcus faecium EF 55 on morphometry and proliferative activity of intestinal mucosa in broilers infected with Salmonella Enteritidis

Directory of Open Access Journals (Sweden)

Ševčíková Zuzana

2016-09-01

Full Text Available Introduction: The present study aimed to investigate the effect of Enterococcus faecium EF55 on chickens, as well as its influence on proliferative activity of epithelial intestinal cells after infection with Salmonella enterica serovar Enteritidis phage type 4 (SE PT4. Moreover, the length and area of duodenal and jejunal villi of the birds were examined.

Proliferative, reparative, and reactive benign bone lesions that may be confused diagnostically with true osseous neoplasms.

LENUS (Irish Health Repository)

Wick, Mark R

2014-01-01

Diagnostic problems attending intraosseous and parosteal pseudoneoplastic lesions can be radiographic, or histological, or both. Proliferations in this category may contain cellular fibro-osseous or chondro-osseous tissues that are difficult to separate microscopically from those seen in various true neoplasms of the bones. This review considers the clinicopathologic features of fibrous dysplasia, benign fibro-osseous lesions of the jawbones, osteofibrous dysplasia, metaphyseal fibrous defect, giant-cell reparative granuloma, "brown tumor" of hyperparathyroidism, synovial chondrometaplasia, aneurysmal bone cyst, tumefactive chronic osteomyelitis, proliferative Paget disease, and polyvinylpyrrolidone storage disease of bone.

Integrated application of combined cooling, heating and power poly-generation PV radiant panel system of zero energy buildings

Science.gov (United States)

Yin, Baoquan

2018-02-01

A new type of combined cooling, heating and power of photovoltaic radiant panel (PV/R) module was proposed, and applied in the zero energy buildings in this paper. The energy system of this building is composed of PV/R module, low temperature difference terminal, energy storage, multi-source heat pump, energy balance control system. Radiant panel is attached on the backside of the PV module for cooling the PV, which is called PV/R module. During the daytime, the PV module was cooled down with the radiant panel, as the temperature coefficient influence, the power efficiency was increased by 8% to 14%, the radiant panel solar heat collecting efficiency was about 45%. Through the nocturnal radiant cooling, the PV/R cooling capacity could be 50 W/m2. For the multifunction energy device, the system shows the versatility during the heating, cooling and power used of building utilization all year round.

Numerical investigations on coupled heat transfer and synthetical performance of a pressurized volumetric receiver with MCRT–FVM method

International Nuclear Information System (INIS)

Cheng, Z.D.; He, Y.L.; Cui, F.Q.

2013-01-01

This paper presents an axisymmetric steady-state computational fluid dynamics model and further studies on the complex coupled heat transfer combined radiation–convection–conduction in the pressurized volumetric receiver (PVR), by combining the Finite Volume Method (FVM) and the Monte Carlo Ray-Trace (MCRT) method. Based on this, effects of geometric parameters of the compound parabolic concentrator (CPC) and properties of the porous absorber on synthetical characteristics and performance of the photo-thermal conversion process in the PVR are further analyzed and discussed detailedly. It is found that the solar flux density distributions are always very heterogeneous with large nonuniformities, and the variation trends of the corresponding temperature distributions are very similar to these but with much lower order of magnitude. The CPC shape determined by the CPC exit aperture has much larger effects on synthetical characteristics and performance of the PVR than that of the CPC entry aperture with a constant acceptance angle. And a suitable or optimal thickness of the porous absorber could be determined by examining where the drastic decreasing trends occur at the curves of variations of synthetical characteristics and performance with the porosity. - Highlights: ► An axisymmetric steady-state CFD model of PVR is presented with MCRT–FVM method. ► The complex coupled heat transfer and synthetical performance of the PVR are studied. ► The effects of geometric parameters and porous properties are analyzed and discussed. ► Solar flux and temperature in PVR are very heterogeneous with large nonuniformities. ► An optimal absorber thickness can be determined by examining the effects of porosity.

Pulmonary venous flow index as a predictor of pulmonary vascular resistance variability in congenital heart disease with increased pulmonary flow: a comparative study before and after oxygen inhalation.

Science.gov (United States)

Rivera, Ivan Romero; Mendonça, Maria Alayde; Andrade, José Lázaro; Moises, Valdir; Campos, Orlando; Silva, Célia Camelo; Carvalho, Antonio Carlos

2013-09-01

There is no definitive and reliable echocardiographic method for estimating the pulmonary vascular resistance (PVR) to differentiate persistent vascular disease from dynamic pulmonary hypertension. The aim of this study was to analyze the relationship between the pulmonary venous blood flow velocity-time integral (VTIpv) and PVR. Eighteen patients (10 females; 4 months to 22 years of age) with congenital heart disease and left to right shunt were studied. They underwent complete cardiac catheterization, including measurements of the PVR and Qp:Qs ratio, before and after 100% oxygen inhalation. Simultaneous left inferior pulmonary venous flow VTIpv was obtained by Doppler echocardiography. The PVR decreased significantly from 5.0 ± 2.6 W to 2.8 ± 2.2 W (P = 0.0001) with a significant increase in the Qp:Qs ratio, from 3.2 ± 1.4 to 4.9 ± 2.4 (P = 0.0008), and the VTIpv increased significantly from 22.6 ± 4.7 cm to 28.1 ± 6.2 cm (P = 0.0002) after 100% oxygen inhalation. VTIpv correlated well with the PVR and Qp:Qs ratio (r = -0.74 and 0.72, respectively). Diagnostic indexes indicated a sensitivity of 86%, specificity of 75%, accuracy of 83%, a positive predictive value of 92% and a negative predictive value of 60%. The VTIpv correlated well with the PVR. The measurement of this index before and after oxygen inhalation may become a useful noninvasive test for differentiating persistent vascular disease from dynamic and flow-related pulmonary hypertension. © 2013, Wiley Periodicals, Inc.

Empirical Formulas for Calculation of Negative Pressure Difference in Vacuum Pipelines

Directory of Open Access Journals (Sweden)

Marek Kalenik

2015-10-01

Full Text Available The paper presents the analysis of results of empirical investigations of a negative pressure difference in vacuum pipelines with internal diameters of 57, 81, 102 mm. The investigations were performed in an experimental installation of a vacuum sewage system, built in a laboratory hall on a scale of 1:1. The paper contains a review of the literature concerning two-phase flows (liquid-gas in horizontal, vertical and diagonal pipelines. It presents the construction and working principles of the experimental installation of vacuum sewage system in steady and unsteady conditions during a two-phase flow of water and air. It also presents a methodology for determination of formula for calculation of a negative pressure difference in vacuum pipelines. The results obtained from the measurements of the negative pressure difference Δpvr in the vacuum pipelines were analyzed and compared with the results of calculations of the negative pressure difference Δpvr, obtained from the determined formula. The values of the negative pressure difference Δpvr calculated for the vacuum pipelines with internal diameters of 57, 81, and 102 mm with the use of Formula (19 coincide with the values of Δpvr measured in the experimental installation of a vacuum sewage system. The dependence of the negative pressure difference Δpvr along the length of the vacuum pipelines on the set negative pressure in the vacuum container pvzp is linear. The smaller the vacuum pipeline diameter, the greater the negative pressure difference Δpvr is along its length.

Possible mechanisms for arsenic-induced proliferative diseases

Energy Technology Data Exchange (ETDEWEB)

Wetterhahn, K.E.; Dudek, E.J.; Shumilla, J.A. [Dartmouth College and Medical School, Hanover, NH (United States)] [and others

1996-12-31

Possible mechanisms for cardiovascular diseases and cancers which have been observed on chronic exposure to arsenic have been investigated. We tested the hypothesis that nonlethal levels of arsenic are mitogenic, cause oxidative stress, increase nuclear translocation of trans-acting factors, and increase expression of genes involved in proliferation. Cultured porcine vascular (from aorta) endothelial cells were used as a model cell system to study the effects of arsenic on the target cells for cardiovascular diseases. Treatment of postconfluent cell cultures with nonovertly toxic concentrations of arsenite increased DNA synthesis, similar to the mitogenic response observed with hydrogen peroxide. Within 1 hour of adding noncytotoxic concentrations of arsenite, cellular levels of oxidants increased relative to control levels, indicating that arsenite promotes cellular oxidations. Arsenite treatment increased nuclear translocation of NF-{kappa}B, an oxidative stress-responsive transcription factor, in a manner similar to that observed with hydrogen peroxide. Pretreatment of intact cells with the antioxidants N-acetylcysteine and dimethylfumarate prevented the arsenite-induced increases in cellular oxidant formation and NF-KB translocation. Arsenite had little or no effect on binding of NF-KB to its DNA recognition sequence in vitro, indicating that it is unlikely that arsenite directly affects NF-KB. The steady-state mRNA levels of intracellular adhesion molecule and urokinase-like plasminogen activator, genes associated with the active endothelial phenotype in arteriosclerosis and cancer metastasis, were increased by nontoxic concentrations of arsenite. These data suggest that arsenite promotes proliferative diseases like heart disease and cancer by activating oxidant-sensitive endothelial cell signaling and gene expression. It is possible that antioxidant therapy would be useful in preventing arsenic-induced cardiovascular disease and cancer.

Is valve choice a significant determinant of paravalular leak post-transcatheter aortic valve implantation? A systematic review and meta-analysis.

LENUS (Irish Health Repository)

O'Sullivan, Katie E

2013-11-01

Paravalvular regurgitation (PVR) following transcatheter aortic valve implantation (TAVI) is associated with poor survival. The two main valve delivery systems used to date differ significantly in both structure and deployment technique. The primary objective of this study was to perform a systematic review and meta-analysis of studies identifying PVR in patients post-TAVI using Medtronic CoreValve (MCV) and Edward Sapien (ES) valves in order to identify whether a significant difference exists between valve types. The secondary objective was to identify additional factors predisposing to PVR to provide an overview of the other associated considerations.

Isoliquiritigenin exhibits anti-proliferative properties in the pituitary independent of estrogen receptor function

International Nuclear Information System (INIS)

Weis, Karen E.; Raetzman, Lori T.

2016-01-01

The plant flavonoid isoliquiritigenin (ISL) is a botanical estrogen widely taken as an herbal supplement to ease the symptoms of menopause. ISL has been also shown to have anti-tumor properties in a number of cancer cell backgrounds. However, the effects of ISL on normal cells are less well known and virtually unstudied in the context of the pituitary gland. We have established a pituitary explant culture model to screen chemical agents for gene expression changes within the pituitary gland during a period of active proliferation and differentiation. Using this whole-organ culture system we found ISL to be weakly estrogenic based on its ability to induce Cckar mRNA expression, an estrogen receptor (ER) mediated gene. Using a range of ISL from 200 nM to 200 μM, we discovered that ISL promoted cell proliferation at a low concentration, yet potently inhibited proliferation at the highest concentration. ICI 182,780 failed to antagonize ISL's repression of pituitary cell proliferation, indicating the effect is independent of ER signaling. Coincident with a decrease in proliferating cells, we observed down-regulation of transcript for cyclin D2 and E2 and a strong induction of mRNA and protein for the cyclin dependent kinase inhibitor Cdkn1a (p21). Importantly, high dose ISL did not alter the balance of progenitor vs. differentiated cell types within the pituitary explants and they seemed otherwise healthy; however, TUNEL staining revealed an increase in apoptotic cell death in ISL treated cultures. Our results merit further examination of ISL as an anti-tumor agent in the pituitary gland. - Highlights: • Isoliquiritigenin possesses weak estrogenic activity based on induction of Cckar. • ISL can be anti-proliferative in pituitary explants without altering cell lineages. • Anti-proliferative behavior of ISL is not estrogen receptor mediated. • ISL induces p21 expression leading to cell cycle arrest and apoptosis.

Isoliquiritigenin exhibits anti-proliferative properties in the pituitary independent of estrogen receptor function

Energy Technology Data Exchange (ETDEWEB)

Weis, Karen E.; Raetzman, Lori T., E-mail: raetzman@life.illinois.edu

2016-12-15

The plant flavonoid isoliquiritigenin (ISL) is a botanical estrogen widely taken as an herbal supplement to ease the symptoms of menopause. ISL has been also shown to have anti-tumor properties in a number of cancer cell backgrounds. However, the effects of ISL on normal cells are less well known and virtually unstudied in the context of the pituitary gland. We have established a pituitary explant culture model to screen chemical agents for gene expression changes within the pituitary gland during a period of active proliferation and differentiation. Using this whole-organ culture system we found ISL to be weakly estrogenic based on its ability to induce Cckar mRNA expression, an estrogen receptor (ER) mediated gene. Using a range of ISL from 200 nM to 200 μM, we discovered that ISL promoted cell proliferation at a low concentration, yet potently inhibited proliferation at the highest concentration. ICI 182,780 failed to antagonize ISL's repression of pituitary cell proliferation, indicating the effect is independent of ER signaling. Coincident with a decrease in proliferating cells, we observed down-regulation of transcript for cyclin D2 and E2 and a strong induction of mRNA and protein for the cyclin dependent kinase inhibitor Cdkn1a (p21). Importantly, high dose ISL did not alter the balance of progenitor vs. differentiated cell types within the pituitary explants and they seemed otherwise healthy; however, TUNEL staining revealed an increase in apoptotic cell death in ISL treated cultures. Our results merit further examination of ISL as an anti-tumor agent in the pituitary gland. - Highlights: • Isoliquiritigenin possesses weak estrogenic activity based on induction of Cckar. • ISL can be anti-proliferative in pituitary explants without altering cell lineages. • Anti-proliferative behavior of ISL is not estrogen receptor mediated. • ISL induces p21 expression leading to cell cycle arrest and apoptosis.

Occupational exposure to anesthetics leads to genomic instability, cytotoxicity and proliferative changes

International Nuclear Information System (INIS)

Souza, Kátina M.; Braz, Leandro G.; Nogueira, Flávia R.; Souza, Marajane B.; Bincoleto, Lahis F.; Aun, Aline G.; Corrente, José E.; Carvalho, Lídia R.; Braz, José Reinaldo C.; Braz, Mariana G.

2016-01-01

Highlights: • Anesthesiologists exposed to the most commonly used anesthetic gases were evaluated. • No alterations were detected for lymphocyte DNA damage detected by the comet assay. • Decreased frequencies of basal cells were detected in exfoliated buccal cells (BMCyt). • Increased frequencies of micronucleus and cytotoxicity were observed in BMCyt assay. • Anesthesiologists have genomic instability due to occupational exposure. - Abstract: Data on the genotoxic and mutagenic effects of occupational exposure to the most frequently used volatile anesthetics are limited and controversial. The current study is the first to evaluate genomic instability, cell death and proliferative index in exfoliated buccal cells (EBC) from anesthesiologists. We also evaluated DNA damage and determined the concentrations of the anesthetic gases most commonly used in operating rooms. This study was conducted on physicians who were allocated into two groups: the exposed group, which consisted of anesthesiologists who had been exposed to waste anesthetic gases (isoflurane, sevoflurane, desflurane and nitrous oxide − N 2 O) for at least two years; and the control group, which consisted of non-exposed physicians matched for age, sex and lifestyle with the exposed group. Venous blood and EBC samples were collected from all participants. Basal DNA damage was evaluated in lymphocytes by the comet assay, whereas the buccal micronucleus (MN) cytome (BMCyt) assay was applied to evaluate genotoxic and cytotoxic effects. The concentrations of N 2 O and anesthetics were measured via a portable infrared spectrophotometer. The average concentration of waste gases was greater than 5 parts per million (ppm) for all of the halogenated anesthetics and was more than 170 ppm for N 2 O, expressed as a time-weighted average. There was no significant difference between the groups in relation to lymphocyte DNA damage. The exposed group had higher frequencies of MN, karyorrhexis and pyknosis, and

Occupational exposure to anesthetics leads to genomic instability, cytotoxicity and proliferative changes

Energy Technology Data Exchange (ETDEWEB)

Souza, Kátina M.; Braz, Leandro G.; Nogueira, Flávia R.; Souza, Marajane B.; Bincoleto, Lahis F.; Aun, Aline G. [Faculdade de Medicina de Botucatu, UNESP − Univ Estadual Paulista, Departamento de Anestesiologia, Botucatu (Brazil); Corrente, José E.; Carvalho, Lídia R. [Instituto de Biociências de Botucatu, UNESP − Univ Estadual Paulista, Departamento de Bioestatística, Botucatu (Brazil); Braz, José Reinaldo C. [Faculdade de Medicina de Botucatu, UNESP − Univ Estadual Paulista, Departamento de Anestesiologia, Botucatu (Brazil); Braz, Mariana G., E-mail: mgbraz@hotmail.com [Faculdade de Medicina de Botucatu, UNESP − Univ Estadual Paulista, Departamento de Anestesiologia, Botucatu (Brazil)

2016-09-15

Highlights: • Anesthesiologists exposed to the most commonly used anesthetic gases were evaluated. • No alterations were detected for lymphocyte DNA damage detected by the comet assay. • Decreased frequencies of basal cells were detected in exfoliated buccal cells (BMCyt). • Increased frequencies of micronucleus and cytotoxicity were observed in BMCyt assay. • Anesthesiologists have genomic instability due to occupational exposure. - Abstract: Data on the genotoxic and mutagenic effects of occupational exposure to the most frequently used volatile anesthetics are limited and controversial. The current study is the first to evaluate genomic instability, cell death and proliferative index in exfoliated buccal cells (EBC) from anesthesiologists. We also evaluated DNA damage and determined the concentrations of the anesthetic gases most commonly used in operating rooms. This study was conducted on physicians who were allocated into two groups: the exposed group, which consisted of anesthesiologists who had been exposed to waste anesthetic gases (isoflurane, sevoflurane, desflurane and nitrous oxide − N{sub 2}O) for at least two years; and the control group, which consisted of non-exposed physicians matched for age, sex and lifestyle with the exposed group. Venous blood and EBC samples were collected from all participants. Basal DNA damage was evaluated in lymphocytes by the comet assay, whereas the buccal micronucleus (MN) cytome (BMCyt) assay was applied to evaluate genotoxic and cytotoxic effects. The concentrations of N{sub 2}O and anesthetics were measured via a portable infrared spectrophotometer. The average concentration of waste gases was greater than 5 parts per million (ppm) for all of the halogenated anesthetics and was more than 170 ppm for N{sub 2}O, expressed as a time-weighted average. There was no significant difference between the groups in relation to lymphocyte DNA damage. The exposed group had higher frequencies of MN, karyorrhexis and

Retinitis pigmentosa reduces the risk of proliferative diabetic retinopathy: a nationwide population-based cohort study.

Directory of Open Access Journals (Sweden)

Yuh-Fang Chen

Full Text Available PURPOSE: To study the association between retinitis pigmentosa (RP and the progression of diabetic retinopathy (DR. METHODS: Using the Longitudinal Health Insurance Database 2000 of Taiwan, we identified individuals with an initial diagnosis for RP during the period of 1997-2008. A non-RP comparison group, 10-fold frequency matched by sex, age, index year and the year of diabetes diagnosed, were randomly selected from the same database. The occurrence of DR was observed for all subjects until the end of 2009. The Kaplan-Meier curves were used to illustrate the cumulative probability of developing DR for the RP group and comparison groups. The hazard ratio (HR of DR for the RP group relative to the comparison group was estimated using Cox proportional hazards model after adjusting for potential confounders. RESULTS: The Kaplan-Meier curves were not statistically significant different between the RP group and the comparison group. However, the RP group had a higher cumulative probability of developing DR during the first six to seven years. The cumulative probability kept increasing and became higher in the comparison group but remained unchanged in the RP group. The HR for the RP patients comparing with the comparison group was 0.96 (95% confidence interval (CI = 0.43-2.14. Stratified by severity, RP was associated with a non-statistically significant reduced risk of proliferative DR (PDR (HR = 0.70, 95% CI = 0.16-3.14. The HR for non-proliferative DR (NPDR was 1.08 (95% CI = 0.40-2.86. CONCLUSION: In this study, RP was not statistically significant associated with the incidence of DR.

Serum level of expressed in renal carcinoma (ERC)/ mesothelin in rats with mesothelial proliferative lesions induced by multi-wall carbon nanotube (MWCNT).

Science.gov (United States)

Sakamoto, Yoshimitsu; Dai, Nakae; Hagiwara, Yoshiaki; Satoh, Kanako; Ohashi, Norio; Fukamachi, Katsumi; Tsuda, Hiroyuki; Hirose, Akihiko; Nishimura, Tetsuji; Hino, Okio; Ogata, Akio

2010-04-01

Expressed in renal carcinoma (ERC)/mesothelin is a good biomarker for human mesothelioma and has been investigated for its mechanistic rationale during the mesothelioma development. Studies are thus ongoing in our laboratories to assess expression of ERC/mesothelin in sera and normal/proliferative/neoplastic mesothelial tissues of animals untreated or given potentially mesothelioma-inducible xenobiotics, by an enzyme-linked immunosorbent assay (ELISA) for N- and C-(terminal fragments of) ERC/mesothelin and immunohistochemistry for C-ERC/mesothelin. In the present paper, we intend to communicate our preliminary data, because this is the first report to show how and from what stage the ERC/mesothelin expression changes during the chemical induction of mesothelial proliferative/neoplatic lesions. Serum N-ERC/mesothelin levels were 51.4 +/- 5.6 ng/ml in control male Fischer 344 rats, increased to 83.6 +/- 11.2 ng/ml in rats given a single intrascrotal administration of 1 mg/kg body weight of multi-wall carbon nanotube (MWCNT) and bearing mesothelial hyperplasia 52 weeks thereafter, and further elevated to 180 +/- 77 ng/ml in rats similarly treated and becoming moribund 40 weeks thereafter, or killed as scheduled at the end of week 52, bearing mesothelioma. While C-ERC/mesothelin was expressed in normal and hyperplastic mesothelia, the protein was detected only in epithelioid mesothelioma cells at the most superficial layer. It is thus suggested that ERC/mesothelin can be used as a biomarker of mesothelial proliferative lesions also in animals, and that the increase of levels may start from the early stage and be enhanced by the progression of the mesothelioma development.

CASE REPORT OF SEVERE PROLIFERATIVE RETINOPATHY IN A PATIENT WITH CONGENITAL LIPODYSTROPHY.

Science.gov (United States)

Rosin, Boris; Jaouni, Tareq

2017-08-21

A case report of a patient with severe proliferative retinopathy due to congenital lipodystrophy. We reviewed the medical history, imaging, and surgical procedures of a 25-year-old woman with a history of congenital lipodystrophy, presenting with bilateral combined tractional and exudative retinal detachment, poorly controlled diabetes mellitus, and extreme dislipidemia. The patient underwent retinal detachment repair surgery both eyes. On the last follow-up, both retinae were flat, and visual acuity had improved in the right eye to J3 for near and finger counting 3 m for distance. Surgery combining pars plana vitrectomy and scleral bucking successfully flattened both retinae and significantly improved visual acuity in one eye in this case of bilateral retinal detachment with combined tractional and exudative components in a patient with congenital lipodystrophy. Surgical control of retinal complications is thus possible, provided there is adequate control of the underlying risk factors.

The evolution of the vertebrate cerebellum: absence of a proliferative external granule layer in a basal ray-finned fish

OpenAIRE

Butts, Thomas; Modrell, Melinda S.; Baker, Clare V. H.; Wingate, Richard J. T.

2014-01-01

The cerebellum represents one of the most morphologically variable structures in the vertebrate brain. To shed light on its evolutionary history, we have examined the molecular anatomy and proliferation of the developing cerebellum of the North American paddlefish, Polyodon spathula. Absence of an external proliferative cerebellar layer and the restriction of Atonal1 expression to the rhombic lip and valvular primordium demonstrate that transit amplification in a cerebellar external germinal ...

Chemical analyses of wasp-associated streptomyces bacteria reveal a prolific potential for natural products discovery

DEFF Research Database (Denmark)

Poulsen, Michael; Oh, Dong-Chan; Clardy, Jon

2011-01-01

and solitary Hymenoptera. Here we test this possibility by examining two species of solitary mud dauber wasps, Sceliphron caementarium and Chalybion californicum. We performed enrichment isolations from 33 wasps and obtained more than 200 isolates of Streptomyces Actinobacteria. Chemical analyses of 15...... and antibacterial activity. The prevalence and anti-microbial properties of Actinobacteria associated with these two solitary wasp species suggest the potential role of these Streptomyces as antibiotic-producing symbionts, potentially helping defend their wasp hosts from pathogenic microbes. Finding...... phylogenetically diverse and chemically prolific Actinobacteria from solitary wasps suggests that insect-associated Actinobacteria can provide a valuable source of novel natural products of pharmaceutical interest....

Use of tylvalosin-medicated feed to control porcine proliferative enteropathy.

Science.gov (United States)

Guedes, R M C; França, S A; Machado, G S; Blumer, M A; da Costa Cruz, E C

2009-09-19

The effect of an oral treatment with the tartrate salt of tylvalosin on the development of proliferative enteropathy in 60 experimentally challenged pigs was studied. Thirty of the pigs were fed a diet medicated with 50 ppm tylvalosin and 30 were fed the unmedicated diet. The treated animals started to receive the medicated feed the day before they were inoculated, and continued to receive it for 14 days. The pigs' bodyweight, feed consumption and clinical signs were evaluated, and they were examined postmortem 20 days after inoculation, and samples of ileum were collected for immunohistochemistry (IHC) for Lawsonia intracellularis. Clinical signs of the disease were more evident in the untreated group than in the treated group. The average daily weight gain, average daily feed consumption and feed conversion efficiency were better in the treated group. The combined length of intestine with lesions was 2847 cm in the untreated group and 183 cm in the treated group. The tylvalosin treatment significantly reduced the level of L intracellularis infection; almost half of the treated pigs were IHC-negative compared with 3.3 per cent of the untreated pigs.

Downregulation of TXNIP leads to high proliferative activity and estrogen-dependent cell growth in breast cancer.

Science.gov (United States)

Park, Jun Won; Lee, Su Hyung; Woo, Gye-Hyung; Kwon, Hyo-Jung; Kim, Dae-Yong

2018-04-06

TXNIP is a potent tumor suppressor with reduced expression in various types of human cancer. The prognostic and predictive power of TXNIP has been recognized in human breast cancer. The aim of this study is to investigate the clinical relevance and functional roles of TXNIP downregulation in breast cancer. We examined TXNIP expression at the protein level in tissue microarray (TMA)-based human breast cancers and its correlation with clinical parameters and molecular markers on immunohistochemistry (IHC). Compared with normal tissues, TXNIP expression was significantly decreased in human breast cancer tissues and animal mammary tumors, along with tumor progression. TXNIP was restored immediately after histone deacetylase inhibitor treatment in breast cancer cells, implying transcriptional regulation of TXNIP by histone modification. Decreased TXNIP protein levels were more common in tumors showing high proliferative activity, such as high Ki-67 labeling indexes and low p27 expression. TXNIP knockdown led to increased in vitro and in vivo breast cancer cell growth accompanied by p27 reduction and GLUT1 induction. Interestingly, estrogen receptor (ER)-positive breast cancer samples showed higher TXNIP expression compared to ER-negative samples. TXNIP expression decreased when ER signaling was activated by estradiol, while its expression increased under ER blockage by anti-estrogen fulvestrant. In addition, TXNIP knockdown in breast cancer cells caused significant reduction in the cell-growth inhibitory effect of anti-estrogen fulvestrant. In conclusion, our data demonstrated that TXNIP functions to suppress high proliferative activity and estrogen-dependent cell growth in breast cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

Human Management of a Wild Plant Modulates the Evolutionary Dynamics of a Gene Determining Recessive Resistance to Virus Infection.

Science.gov (United States)

Poulicard, Nils; Pacios, Luis Fernández; Gallois, Jean-Luc; Piñero, Daniel; García-Arenal, Fernando

2016-08-01

This work analyses the genetic variation and evolutionary patterns of recessive resistance loci involved in matching-allele (MA) host-pathogen interactions, focusing on the pvr2 resistance gene to potyviruses of the wild pepper Capsicum annuum glabriusculum (chiltepin). Chiltepin grows in a variety of wild habitats in Mexico, and its cultivation in home gardens started about 25 years ago. Potyvirus infection of Capsicum plants requires the physical interaction of the viral VPg with the pvr2 product, the translation initiation factor eIF4E1. Mutations impairing this interaction result in resistance, according to the MA model. The diversity of pvr2/eIF4E1 in wild and cultivated chiltepin populations from six biogeographical provinces in Mexico was analysed in 109 full-length coding sequences from 97 plants. Eleven alleles were found, and their interaction with potyvirus VPg in yeast-two-hybrid assays, plus infection assays of plants, identified six resistance alleles. Mapping resistance mutations on a pvr2/eIF4E1 model structure showed that most were around the cap-binding pocket and strongly altered its surface electrostatic potential, suggesting resistance-associated costs due to functional constraints. The pvr2/eIF4E1 phylogeny established that susceptibility was ancestral and resistance was derived. The spatial structure of pvr2/eIF4E1 diversity differed from that of neutral markers, but no evidence of selection for resistance was found in wild populations. In contrast, the resistance alleles were much more frequent, and positive selection stronger, in cultivated chiltepin populations, where diversification of pvr2/eIF4E1 was higher. This analysis of the genetic variation of a recessive resistance gene involved in MA host-pathogen interactions in populations of a wild plant show that evolutionary patterns differ according to the plant habitat, wild or cultivated. It also demonstrates that human management of the plant population has profound effects on the

Human Management of a Wild Plant Modulates the Evolutionary Dynamics of a Gene Determining Recessive Resistance to Virus Infection.

Directory of Open Access Journals (Sweden)

Nils Poulicard

2016-08-01

Full Text Available This work analyses the genetic variation and evolutionary patterns of recessive resistance loci involved in matching-allele (MA host-pathogen interactions, focusing on the pvr2 resistance gene to potyviruses of the wild pepper Capsicum annuum glabriusculum (chiltepin. Chiltepin grows in a variety of wild habitats in Mexico, and its cultivation in home gardens started about 25 years ago. Potyvirus infection of Capsicum plants requires the physical interaction of the viral VPg with the pvr2 product, the translation initiation factor eIF4E1. Mutations impairing this interaction result in resistance, according to the MA model. The diversity of pvr2/eIF4E1 in wild and cultivated chiltepin populations from six biogeographical provinces in Mexico was analysed in 109 full-length coding sequences from 97 plants. Eleven alleles were found, and their interaction with potyvirus VPg in yeast-two-hybrid assays, plus infection assays of plants, identified six resistance alleles. Mapping resistance mutations on a pvr2/eIF4E1 model structure showed that most were around the cap-binding pocket and strongly altered its surface electrostatic potential, suggesting resistance-associated costs due to functional constraints. The pvr2/eIF4E1 phylogeny established that susceptibility was ancestral and resistance was derived. The spatial structure of pvr2/eIF4E1 diversity differed from that of neutral markers, but no evidence of selection for resistance was found in wild populations. In contrast, the resistance alleles were much more frequent, and positive selection stronger, in cultivated chiltepin populations, where diversification of pvr2/eIF4E1 was higher. This analysis of the genetic variation of a recessive resistance gene involved in MA host-pathogen interactions in populations of a wild plant show that evolutionary patterns differ according to the plant habitat, wild or cultivated. It also demonstrates that human management of the plant population has profound

Paradoxical expression of INK4c in proliferative multiple myeloma tumors: bi-allelic deletion vs increased expression

Directory of Open Access Journals (Sweden)

Hanamura Ichiro

2006-10-01

Full Text Available Abstract Background A high proliferative capacity of tumor cells usually is associated with shortened patient survival. Disruption of the RB pathway, which is critically involved in regulating the G1 to S cell cycle transition, is a frequent target of oncogenic events that are thought to contribute to increased proliferation during tumor progression. Previously, we determined that p18INK4c, an essential gene for normal plasma cell differentiation, was bi-allelically deleted in five of sixteen multiple myeloma (MM cell lines. The present study was undertaken to investigate a possible role of p18INK4c in increased proliferation of myeloma tumors as they progress. Results Thirteen of 40 (33% human myeloma cell lines do not express normal p18INK4c, with bi-allelic deletion of p18 in twelve, and expression of a mutated p18 fragment in one. Bi-allelic deletion of p18, which appears to be a late progression event, has a prevalence of about 2% in 261 multiple myeloma (MM tumors, but the prevalence is 6 to10% in the 50 tumors with a high expression-based proliferation index. Paradoxically, 24 of 40 (60% MM cell lines, and 30 of 50 (60% MM tumors with a high proliferation index express an increased level of p18 RNA compared to normal bone marrow plasma cells, whereas this occurs in only five of the 151 (3% MM tumors with a low proliferation index. Tumor progression is often accompanied by increased p18 expression and an increased proliferation index. Retroviral-mediated expression of exogenous p18 results in marked growth inhibition in three MM cell lines that express little or no endogenous p18, but has no effect in another MM cell line that already expresses a high level of p18. Conclusion Paradoxically, although loss of p18 appears to contribute to increased proliferation of nearly 10% of MM tumors, most MM cell lines and proliferative MM tumors have increased expression of p18. Apart from a small fraction of cell lines and tumors that have inactivated

The outcomes of pars plana vitrectomy without endotamponade for tractional retinal detachment secondary to proliferative diabetic retinopathy

Directory of Open Access Journals (Sweden)

Rao Muhammad Rashad Qamar

2013-10-01

Full Text Available AIM: To evaluate the outcomes of pars plana vitrectomy (PPV without the use of an ocular tamponade in patients having tractional retinal detachment (TRD secondary to proliferative diabetic retinopathy (PDR.METHODS: It was an interventional study conducted at the Department of Ophthalmology, B.V. Hospital, Bahawalpur, Pakistan, from July 2011 to July 2012. A total of 75 patients (84 eyes having TRD secondary to PDR were treated by PPV without using an ocular tamponade. All patients included in the study had a tractional retinal detachment secondary to proliferative diabetic retinopathy but didn’t have or develop retinal breaks before or during the study period. The surgical procedure included a PPV combined with the removal of the tractional retinal membranes and the application of endolaser photocoagulation to the retina. The mean follow-up period was 12 months.RESULTS:Successful retinal reattachement was observed in 78 of the operated eyes (92.8%. In these patients, the retina remained attached till the end of the one year follow-up period. Improvement in best corrected visual acuity (BCVA was seen in 63 eyes (75%. The visual acuity remained unchanged in 9 eyes (10.7%. Mean improvement in BCVA was 2.00+1.24 at baseline to 1.24+1.22 (PCONCLUSION: In the absence of the retinal breaks, a TRD secondary to PDR can be successfully treated by pars plana vitrectomy without the use of an ocular tamponade.

Regional control of Drosophila gut stem cell proliferation: EGF establishes GSSC proliferative set point & controls emergence from quiescence.

Science.gov (United States)

Strand, Marie; Micchelli, Craig A

2013-01-01

Adult stem cells vary widely in their rates of proliferation. Some stem cells are constitutively active, while others divide only in response to injury. The mechanism controlling this differential proliferative set point is not well understood. The anterior-posterior (A/P) axis of the adult Drosophila midgut has a segmental organization, displaying physiological compartmentalization and region-specific epithelia. These distinct midgut regions are maintained by defined stem cell populations with unique division schedules, providing an excellent experimental model with which to investigate this question. Here, we focus on the quiescent gastric stem cells (GSSCs) of the acidic copper cell region (CCR), which exhibit the greatest period of latency between divisions of all characterized gut stem cells, to define the molecular basis of differential stem cell activity. Our molecular genetic analysis demonstrates that the mitogenic EGF signaling pathway is a limiting factor controlling GSSC proliferation. We find that under baseline conditions, when GSSCs are largely quiescent, the lowest levels of EGF ligands in the midgut are found in the CCR. However, acute epithelial injury by enteric pathogens leads to an increase in EGF ligand expression in the CCR and rapid expansion of the GSSC lineage. Thus, the unique proliferative set points for gut stem cells residing in physiologically distinct compartments are governed by regional control of niche signals along the A/P axis.

Regional control of Drosophila gut stem cell proliferation: EGF establishes GSSC proliferative set point & controls emergence from quiescence.

Directory of Open Access Journals (Sweden)

Marie Strand

Full Text Available Adult stem cells vary widely in their rates of proliferation. Some stem cells are constitutively active, while others divide only in response to injury. The mechanism controlling this differential proliferative set point is not well understood. The anterior-posterior (A/P axis of the adult Drosophila midgut has a segmental organization, displaying physiological compartmentalization and region-specific epithelia. These distinct midgut regions are maintained by defined stem cell populations with unique division schedules, providing an excellent experimental model with which to investigate this question. Here, we focus on the quiescent gastric stem cells (GSSCs of the acidic copper cell region (CCR, which exhibit the greatest period of latency between divisions of all characterized gut stem cells, to define the molecular basis of differential stem cell activity. Our molecular genetic analysis demonstrates that the mitogenic EGF signaling pathway is a limiting factor controlling GSSC proliferation. We find that under baseline conditions, when GSSCs are largely quiescent, the lowest levels of EGF ligands in the midgut are found in the CCR. However, acute epithelial injury by enteric pathogens leads to an increase in EGF ligand expression in the CCR and rapid expansion of the GSSC lineage. Thus, the unique proliferative set points for gut stem cells residing in physiologically distinct compartments are governed by regional control of niche signals along the A/P axis.

Pulmonary valve replacement after operative repair of tetralogy of Fallot: meta-analysis and meta-regression of 3,118 patients from 48 studies.

Science.gov (United States)

Ferraz Cavalcanti, Paulo Ernando; Sá, Michel Pompeu Barros Oliveira; Santos, Cecília Andrade; Esmeraldo, Isaac Melo; de Escobar, Rodrigo Renda; de Menezes, Alexandre Motta; de Azevedo, Orlando Morais; de Vasconcelos Silva, Frederico Pires; Lins, Ricardo Felipe de Albuquerque; Lima, Ricardo de Carvalho

2013-12-10

Because the real benefit of pulmonary valve replacement (PVR) in patients with repaired tetralogy of Fallot who develop pulmonary insufficiency remains unclear, it is necessary to analyze the evidence published around the world. We performed a systematic review of studies that reported data about the effect of PVR in patients with repaired tetralogy of Fallot that developed pulmonary insufficiency, until December 2012. The variables chosen to represent the benefit were both right ventricular (RV) and left ventricular measures, QRS duration, and functional class. The principal summary measures were difference in means with 95% confidence interval and p values (considered statistically significant when p regression were completed with the software Comprehensive Meta-Analysis (version 2, Biostat, Inc., Englewood, New Jersey). Forty-eight studies involving 3,118 patients met the eligibility criteria. The pooled 30-day mortality was 0.87% (47 studies; 27 of 3,100 patients); the pooled 5-year mortality was 2.2% (24 studies; 49 of 2,231 patients); the pooled 5-year re-PVR was 4.9% (15 studies; 88 of 1,798 patients). The results of this meta-analysis demonstrate that after PVR: 1) the RV experiences improvement of its volumes and function; 2) the left ventricle experiences improvement of its function; 3) QRS duration decreases; 4) symptoms improve; 5) pre-operative RV geometry modulates the effect of PVR; and 6) there is important heterogeneity of the effects among the studies, and few publication biases. In conclusion, PVR seems to be a positive approach in the analyzed scenario. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

The study of diagnostic efficacy of MR spectroscopy in prostate cancer

International Nuclear Information System (INIS)

Ye Jintang; Guo Xuemei; Wang Xiaoying; Li Feiyu; Jiang Xuexiang

2009-01-01

Objective: To evaluate the diagnostic efficacy of MRS in prostate cancer based on sextant localization. Methods: There were 110 patients, 54 patients with pathologically confirmed prostate cancer and 56 patients confirmed non-prostate cancer proved by ultrasound guided systemic biopsy. The (choline + creatine) / citrate (CC/C) value in each voxel and ratio of positive voxel (PVR) in sextant localization were measured. The ROC analysis was used to evaluate the diagnostic efficacy of CC/C in single voxel and PVR in sextant localization. Results: There are 1673 and 2426 voxel in prostate cancer and non-prostate cancer respectively. The median of CC/C in cancer sextants was 2.137; the median of CC/C in noncancer sextants was 0.600. The difference of these two groups was statistically significant (Z = -41.7, P < 0.01). The diagnostic sensitivity was 81.4% (1362/1673), the specificity was 83.1% (2018/2426), and the accuracy was 82.4% [(1362 + 2018)/4099] for prostatic cancer with the cutoff point 0.911 of the CC/C value. The median of PVR in cancer sextants and noncancer sextants were 1 and 0 respectively, the difference of PVR was statistically significant ( Z =-11.7, P < 0.01). The diagnostic sensitivity was 77.5% (148/191), the specificity was 76.9% (247/321), and the accuracy was 77.1%[(148 + 247)/512] for prostatic cancer with the cutoff point 0.519 of the PVR. Conclusion: Detecting the cutoff point of the CC/C value in single voxel and the PVR in sextant localization may be valuable in the diagnosis of prostate cancer. (authors)

Health assessment of environmental pollutants: proliferative and degenerative diseases

International Nuclear Information System (INIS)

Stuart, B.O.

1988-01-01

In order to achieve a balanced approach to risk assessment between carcinogenic and non-carcinogenic health effects one must examine the risk of disease or death in the general population exposed to a particular air pollutant that can be related quantitatively to intensity and duration of exposures (National Academy of Sciences, 1983). Such risk assessment should be based upon careful evaluation of scientific findings of dose-response relationships in the chronically exposed population. Quantitative assessment of environmentally produced disease in man has proven to be complex and demanding. A variety of factors play important roles in this task. As an example, there are induction-latency periods for chronic diseases, including cancer, which may range from five to twenty-five years. The diseases themselves, whether proliferative or degenerative, may follow several stages of progression. There is only sparse epidemiological data on serious health effects that may be due to environmental as compared to occupational exposures. Exposures to chemical or radiological air contaminants do not occur singly but to a multiplicity of agents, and disease processes are frequently markedly affected by the interaction of a variety of factors, particularly that of cigarette smoking. There is growing recognition of potentially sensitive subpopulations, including the elderly and the very young, but adequate techniques for assessing the magnitude of increased risks to these groups have not yet been developed

Hepatic progenitor cell resistance to TGF-β1's proliferative and apoptotic effects

International Nuclear Information System (INIS)

Clark, J. Brian; Rice, Lisa; Sadiq, Tim; Brittain, Evan; Song, Lujun; Wang Jian; Gerber, David A.

2005-01-01

The success of hepatocellular therapies using stem or progenitor cell populations is dependent upon multiple factors including the donor cell, microenvironment, and etiology of the liver injury. The following experiments investigated the impact of TGF-β1 on a previously described population of hepatic progenitor cells (HPC). The majority of the hepatic progenitor cells were resistant to endogenously produced TGF-β1's proapoptotic and anti-proliferative effects unlike more well-differentiated cellular populations (e.g., mature hepatocytes). Surprisingly, in vitro TGF-β1 supplementation significantly inhibited de novo hepatic progenitor cell colony formation possibly via an indirect mechanism(s). Therefore despite the HPC's direct resistance to supplemental TGF-β1, this cytokine's inhibitory effect on colony formation could have a potential negative impact on the use of these cells as a therapy for patients with liver disease

Mitochondrial localization of the low level p53 protein in proliferative cells

Energy Technology Data Exchange (ETDEWEB)

Ferecatu, Ioana; Bergeaud, Marie; Rodriguez-Enfedaque, Aida; Le Floch, Nathalie [Laboratoire de Genetique et Biologie Cellulaire - CNRS UMR 8159, Universite de Versailles Saint-Quentin-en-Yvelines, Versailles, France and Laboratoire de Genetique Moleculaire et Physiologique, Ecole Pratique des Hautes Etudes, Versailles (France); Oliver, Lisa [INSERM U601, Universite de Nantes, Faculte de Medecine, Nantes Cedex (France); Rincheval, Vincent; Renaud, Flore [Laboratoire de Genetique et Biologie Cellulaire - CNRS UMR 8159, Universite de Versailles Saint-Quentin-en-Yvelines, Versailles, France and Laboratoire de Genetique Moleculaire et Physiologique, Ecole Pratique des Hautes Etudes, Versailles (France); Vallette, Francois M. [INSERM U601, Universite de Nantes, Faculte de Medecine, Nantes Cedex (France); Mignotte, Bernard [Laboratoire de Genetique et Biologie Cellulaire - CNRS UMR 8159, Universite de Versailles Saint-Quentin-en-Yvelines, Versailles, France and Laboratoire de Genetique Moleculaire et Physiologique, Ecole Pratique des Hautes Etudes, Versailles (France); Vayssiere, Jean-Luc, E-mail: jean-luc.vayssiere@uvsq.fr [Laboratoire de Genetique et Biologie Cellulaire - CNRS UMR 8159, Universite de Versailles Saint-Quentin-en-Yvelines, Versailles, France and Laboratoire de Genetique Moleculaire et Physiologique, Ecole Pratique des Hautes Etudes, Versailles (France)

2009-10-02

p53 protein plays a central role in suppressing tumorigenesis by inducing cell cycle arrest or apoptosis through transcription-dependent and -independent mechanisms. Emerging publications suggest that following stress, a fraction of p53 translocates to mitochondria to induce cytochrome c release and apoptosis. However, the localization of p53 under unstressed conditions remains largely unexplored. Here we show that p53 is localized at mitochondria in absence of apoptotic stimuli, when cells are proliferating, localization observed in various cell types (rodent and human). This is also supported by acellular assays in which p53 bind strongly to mitochondria isolated from rat liver. Furthermore, the mitochondria subfractionation study and the alkaline treatment of the mitochondrial p53 revealed that the majority of mitochondrial p53 is present in the membranous compartments. Finally, we identified VDAC, a protein of the mitochondrial outer-membrane, as a putative partner of p53 in unstressed/proliferative cells.

Mitochondrial localization of the low level p53 protein in proliferative cells

International Nuclear Information System (INIS)

Ferecatu, Ioana; Bergeaud, Marie; Rodriguez-Enfedaque, Aida; Le Floch, Nathalie; Oliver, Lisa; Rincheval, Vincent; Renaud, Flore; Vallette, Francois M.; Mignotte, Bernard; Vayssiere, Jean-Luc

2009-01-01

p53 protein plays a central role in suppressing tumorigenesis by inducing cell cycle arrest or apoptosis through transcription-dependent and -independent mechanisms. Emerging publications suggest that following stress, a fraction of p53 translocates to mitochondria to induce cytochrome c release and apoptosis. However, the localization of p53 under unstressed conditions remains largely unexplored. Here we show that p53 is localized at mitochondria in absence of apoptotic stimuli, when cells are proliferating, localization observed in various cell types (rodent and human). This is also supported by acellular assays in which p53 bind strongly to mitochondria isolated from rat liver. Furthermore, the mitochondria subfractionation study and the alkaline treatment of the mitochondrial p53 revealed that the majority of mitochondrial p53 is present in the membranous compartments. Finally, we identified VDAC, a protein of the mitochondrial outer-membrane, as a putative partner of p53 in unstressed/proliferative cells.

Proliferative activity of elastin-like-peptides depends on charge and phase transition.

Science.gov (United States)

Yuan, Yuan; Koria, Piyush

2016-03-01

Elastin-like-peptides (ELPs) are stimulus-responsive protein-based polymers and are attractive biomaterials due to their biocompatibility and unique properties. This study shows that in addition to their physical properties, ELPs have biological activities that are conducive to tissue regeneration. Specifically, we found that ELPs induce fibroblast proliferation via cell surface heparan sulfate proteoglycans (HSPG). Furthermore, our data suggests that ELP based materials with differential proliferative potential can be designed by controlling the interaction of ELPs with HSPGs by incorporating either hydrophobic or positively charged residues within the ELP sequence. Fibroblast proliferation is important for granulation tissue formation which is important in chronic wounds as well as in healing of other tissues. The customizable biological activity of ELPs coupled with their unique physical properties will enable us to design novel, sustainable and cost effective therapies for different tissue regeneration applications. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 697-706, 2016. © 2015 Wiley Periodicals, Inc.

The expression of the Slit-Robo signal in the retina of diabetic rats and the vitreous or fibrovascular retinal membranes of patients with proliferative diabetic retinopathy.

Science.gov (United States)

Zhou, Weiyan; Wang, Hongya; Yu, Wenzhen; Xie, Wankun; Zhao, Min; Huang, Lvzhen; Li, Xiaoxin

2017-01-01

The Slit-Robo signal has an important role in vasculogenesis and angiogenesis. Our study examined the expression of Slit2 and its receptor, Robo1, in a rat model of streptozotocin-induced diabetes and in patients with proliferative diabetic retinopathy. Diabetes was induced in male Sprague-Dawley rats via a single, intraperitoneal injection of streptozotocin. The rats were sacrificed 1, 3 or 6 months after the injection. The expression of Slit2 and Robo1 in retinal tissue was measured by real-time reverse transcription polymerase chain reaction (RT-PCR), and protein levels were measured by western blotting and immunohistochemistry. Recombinant N-Slit2 protein was used to study the effects of Slit2 on the expression of VEGF in vivo. The concentration of Slit2 protein in human eyes was measured by enzyme-linked immunosorbent assay in 27 eyes with proliferative diabetic retinopathy and 28 eyes in control group. The expression of Slit2, Robo1 and VEGF in the excised human fibrovascular membranes was examined by fluorescence immunostaining and semi-quantitative RT-PCR. The expression of Slit2 and Robo1 in the retina was altered after STZ injection. Recombinant N-Slit2 protein did not increase the retinal VEGF expression. Vitreous concentrations of Slit2 were significantly higher in the study group than in the control group. In the human fibrovascular membranes of the study group, the co-localization of VEGF with the markers for Slit2 and Robo1was observed. The expression of Slit2 mRNA, Robo1 mRNA, and VEGF mRNA was significantly higher in human fibrovascular proliferative diabetic retinopathy membranes than in the control membranes. The alteration of Slit2 and Robo1 expression in the retinas of diabetic rats and patients with proliferative diabetic retinopathy suggests a role for the Slit-Robo signal in the various stages diabetic retinopathy. Further studies should address the possible involvement of the Slit-Robo signal in the pathophysiological progress of diabetic

Unnoticed Post-Void Residual Urine Volume in People with Moderate to Severe Intellectual Disabilities: Prevalence and Risk Factors

Science.gov (United States)

de Waal, K. H.; Tinselboer, B. M.; Evenhuis, H. M.; Penning, C.

2009-01-01

Background: Increased post-void residual urine volume (PVR) is often seen in geriatric populations. People with intellectual disabilities (ID) have risk factors in common with these populations. Aims: To investigate in adults with ID: (1) Feasibility of portable ultrasound bladder scanning; (2) Prevalence of PVR; and (3) Relations with proposed…

77 FR 47921 - Pecos Valley Permian Railroad, L.L.C. d/b/a Pecos Valley Southern Railway Company-Lease Exemption...

Science.gov (United States)

2012-08-10

... rail carrier. As a result of this transaction, PVR will provide common carrier rail service over the rail lines owned by PVS between Pecos and Saragosa. PVR states that the lease agreement between PVS and... the Pecos Valley Southern Railway Company (PVS) and operate 24 miles of rail line located between...

Proliferative Activity of Mammary Carcinoma Cells by AgNOR Count in C3H mice Receiving Ethanol Extract of Sponge Haliclona sp

Science.gov (United States)

Sijabat, Lanceria; Susilaningsih, Neni; Trianto, Agus; Murwani, Retno

2018-02-01

Quantification of argyrophilic nucleolar organizer region (AgNORs) was considered as one of markers of proliferative activity of cancer cells. Sponge Haliclona sp extract contains anticancer bioactive compounds and our previous study showed that the extract was able to improve histological grade of induced mammary adenocarcinoma in mice. The following research was conducted to study the extract administration on the proliferative activity of the carcinoma cells represented by AgNOR count in mice. This experimental study applied post test only control group design. Twenty C3H mice were divided into four groups namely C (control), H1, H2 and H3. Each group was given 0, 0.15, 1.5, and 15 mg Haliclona sp extract respectively. After three weeks of extract administration, mice were inoculated with breast cancer cells from donor mice. The extract administration were continued for another three weeks. AgNOR count was performed on tumor sections and expressed as mean of AgNOR (mAgNOR) and percentage of AgNOR (pAgNOR). Means of mAgNOR in C, H1, H2 and H3 were 4.070, 3.195, 3.450, and 3.190 respectively. Means of pAgNOR in C, H1, H2 and H3 were 34,40, 25,40, 38,40 and 19,80 respectively. The lowest means of mAgNOR and pAgNOR which is an indication of lower proliferative activity of the cancer cells was found in H3. However no significant difference can be found among treatment groups (p>0.05). Using AgNOR count, the ethanol extract of Haliclona sp could not show significant reduction in proliferation of mammary carcinoma cells of C3H mice. This finding support the view that AgNOR alone could not be used to determine pathology of cancer cells.

Detection of Glutamate and γ-aminobutyric Acid in Vitreous of Patients with Proliferative Diabetic Retinopathy

Institute of Scientific and Technical Information of China (English)

Juan Deng; De-Zheng Wu; Rulong Gao

2000-01-01

Purpose: To study the levels of glutamate and γ-aminobutyric acid (GABA) in vitreous of patients with proliferative diabetic retinopathy(PDR) and to investigate their roles in retinal ischemia.Method: Vitreous samples were collected from 25 patients (27 eyes) with PDR and 14patients ( 14 eyes) with idiopathic macular hole. Glutamate and GABA detection were performed by high-performance liquid chromatography (HPLC).Results: Patients with PDR had significantly higher concentrations of glutamate and GABA than the control group. The glutamate level has a significantly positive correlation with GABA level.Conclusion: Detection of glutamate and GABA in vitreous provides biochemical support for the mechanism and treatment of ischemic retinal damage in patients with PDR.

Noninvasive Evaluation of Cellular Proliferative Activity in Brain Neurogenic Regions in Rats under Depression and Treatment by Enhanced [18F]FLT-PET Imaging.

Science.gov (United States)

Tamura, Yasuhisa; Takahashi, Kayo; Takata, Kumi; Eguchi, Asami; Yamato, Masanori; Kume, Satoshi; Nakano, Masayuki; Watanabe, Yasuyoshi; Kataoka, Yosky

2016-08-03

Neural stem cells in two neurogenic regions, the subventricular zone and the subgranular zone (SGZ) of the hippocampal dentate gyrus, can divide and produce new neurons throughout life. Hippocampal neurogenesis is related to emotions, including depression/anxiety, and the therapeutic effects of antidepressants, as well as learning and memory. The establishment of in vivo imaging for proliferative activity of neural stem cells in the SGZ might be used to diagnose depression and to monitor the therapeutic efficacy of antidepressants. Positron emission tomography (PET) imaging with 3'-deoxy-3'-[(18)F]fluoro-l-thymidine ([(18)F]FLT) has been studied to allow visualization of proliferative activity in two neurogenic regions of adult mammals; however, the PET imaging has not been widely used because of lower accumulation of [(18)F]FLT, which does not allow quantitative assessment of the decline in cellular proliferative activity in the SGZ under the condition of depression. We report the establishment of an enhanced PET imaging method with [(18)F]FLT combined with probenecid, an inhibitor of drug transporters at the blood-brain barrier, which can allow the quantitative visualization of neurogenic activity in rats. Enhanced PET imaging allowed us to evaluate reduced cell proliferation in the SGZ of rats with corticosterone-induced depression, and further the recovery of proliferative activity in rats under treatment with antidepressants. This enhanced [(18)F]FLT-PET imaging technique with probenecid can be used to assess the dynamic alteration of neurogenic activity in the adult mammalian brain and may also provide a means for objective diagnosis of depression and monitoring of the therapeutic effect of antidepressant treatment. Adult hippocampal neurogenesis may play a role in major depression and antidepressant therapy. Establishment of in vivo imaging for hippocampal neurogenic activity may be useful to diagnose depression and monitor the therapeutic efficacy of

The evolution of the vertebrate cerebellum: absence of a proliferative external granule layer in a non-teleost ray-finned fish

OpenAIRE

Butts, Thomas; Modrell, Melinda Sue; Baker, Clare Victoria; Wingate, Richard JT

2014-01-01

The cerebellum represents one of the most morphologically variable structures in the vertebrate brain. To shed light on its evolutionary history, we have examined the molecular anatomy and proliferation of the developing cerebellum of the North American paddlefish, Polyodon spathula. Absence of an external proliferative cerebellar layer and the restriction of Atonal1 expression to the rhombic lip and valvular primordium demonstrate that transit amplification in a cerebellar external germinal ...

Proliferative vitreo-retinal disorders: experimental models in vivo and in vitro.

Science.gov (United States)

Martini, B

1992-01-01

The aim of the present thesis was to develop, refine, and assess experimental models for the study of proliferative vitreo-retinal disorders. An intravitreal injection of a colloidal solution of microparticles was used in the primate eye to produce pathologic changes including intraocular cell invasion, cell proliferation, neovascularization, collagen synthesis, and tractional retinal detachment. In a separate primate model for laser-induced subretinal neovascularization, the origin and the occurrence of macrophages was evaluated. Examinations were performed using ophthalmoscopy, slit-lamp microscopy, light microscopy, and transmission electron microscopy. Cell cultures were employed to study the effects of vitreous humor and macrophages on the proliferation of cultured retinal pigment epithelial (RPE) cells and cultured fibroblasts using a Coulter counter. Morphologic changes were documented by phase micrography. A quantitative estimation of the extracellular matrix deposition of fibrous proteins by macrophage-modulated RPE cells as well as by vitreous-modulated RPE cells was done using enzymatic digestion and radioactive labeling techniques. A qualitative analysis of the types of collagen that was deposited in the extracellular matrices by vitreous modulated cultures was also made using indirect immunofluorescence. Using a newly developed RPE cell specific monoclonal antibody, the avidin-biotin-peroxidase labeling technique was finally employed to test the phenotypic epitope expression of macrophage-modulated and non-modulated RPE cells. A new experimental in vivo model for pathologic changes that characterize proliferative vitreo-retinal disorders was developed in the primate eye. In the model for laser-induced subretinal neovascularization, macrophages were shown to be principally recruited from the systemic circulation. Using cell cultures, it was found that both macrophage-conditioned medium and vitreous humor, separately or combined, exert mitogenic effects

An APC:WNT counter-current-like mechanism regulates cell division along the colonic crypt axis: a mechanism that explains how APC mutations induce proliferative abnormalities that drive colon cancer development.

Directory of Open Access Journals (Sweden)

Bruce M Boman

2013-11-01

Full Text Available APC normally down-regulates WNT signaling in human colon, and APC mutations cause proliferative abnormalities in premalignant crypts leading to colon cancer, but the mechanisms are unclear at the level of spatial and functional organization of the crypt. Accordingly, we postulated a counter-current-like mechanism based on gradients of factors (APC;WNT that regulate colonocyte proliferation along the crypt axis. During crypt renewal, stem cells (SCs at the crypt bottom generate non-SC daughter cells that proliferate and differentiate while migrating upwards. The APC concentration is low at the crypt bottom and high at the top (where differentiated cells reside. WNT signaling, in contrast, is high at the bottom (where SCs reside and low at the top. Given that WNT and APC gradients are counter to one another, we hypothesized that a counter-current-like mechanism exists. Since both APC and WNT signaling components (e.g. survivin are required for mitosis, this mechanism establishes a zone in the lower crypt where conditions are optimal for maximal cell division and mitosis orientation (symmetric versus asymmetric. APC haploinsufficiency diminishes the APC gradient, shifts the proliferative zone upwards, and increases symmetric division, which causes SC overpopulation. In homozygote mutant crypts, these changes are exacerbated. Thus, APC-mutation-induced changes in the counter-current-like mechanism cause expansion of proliferative populations (SCs, rapidly-proliferating cells during tumorigenesis. We propose this mechanism also drives crypt fission, functions in the crypt cycle, and underlies adenoma development. Novel chemoprevention approaches designed to normalize the two gradients and readjust the proliferative zone downwards, might thwart progression of these premalignant changes.

The nontoxic natural compound Curcumin exerts anti-proliferative, anti-migratory, and anti-invasive properties against malignant gliomas

International Nuclear Information System (INIS)

Senft, Christian; Polacin, Margareth; Priester, Maike; Seifert, Volker; Kögel, Donat; Weissenberger, Jakob

2010-01-01

New drugs are constantly sought after to improve the survival of patients with malignant gliomas. The ideal substance would selectively target tumor cells without eliciting toxic side effects. Here, we report on the anti-proliferative, anti-migratory, and anti-invasive properties of the natural, nontoxic compound Curcumin observed in five human glioblastoma (GBM) cell lines in vitro. We used monolayer wound healing assays, modified Boyden chamber trans-well assays, and cell growth assays to quantify cell migration, invasion, and proliferation in the absence or presence of Curcumin at various concentrations. Levels of the transcription factor phospho-STAT3, a potential target of Curcumin, were determined by sandwich-ELISA. Subsequent effects on transcription of genes regulating the cell cycle were analyzed by quantitative real-time PCR. Effects on apoptosis were determined by caspase assays. Curcumin potently inhibited GBM cell proliferation as well as migration and invasion in all cell lines contingent on dose. Simultaneously, levels of the biologically active phospho-STAT3 were decreased and correlated with reduced transcription of the cell cycle regulating gene c-Myc and proliferation marking Ki-67, pointing to a potential mechanism by which Curcumin slows tumor growth. Curcumin is part of the diet of millions of people every day and is without known toxic side effects. Our data show that Curcumin bears anti-proliferative, anti-migratory, and anti-invasive properties against GBM cells in vitro. These results warrant further in vivo analyses and indicate a potential role of Curcumin in the treatment of malignant gliomas

A shift in the balance of vascular endothelial growth factor and connective tissue growth factor by bevacizumab causes the angiofibrotic switch in proliferative diabetic retinopathy

NARCIS (Netherlands)

van Geest, Rob J.; Lesnik-Oberstein, Sarit Y.; Tan, H. Stevie; Mura, Marco; Goldschmeding, Roel; van Noorden, Cornelis J. F.; Klaassen, Ingeborg; Schlingemann, Reinier O.

2012-01-01

Introduction In proliferative diabetic retinopathy (PDR), vascular endothelial growth factor (VEGF) and connective tissue growth factor (CTGF) may cause blindness by neovascularisation followed by fibrosis of the retina. It has previously been shown that a shift in the balance between levels of CTGF

Acute renal failure due to mesangial proliferative glomerulonephritis in a pregnant woman with primary Sjögren's syndrome.

Science.gov (United States)

Adam, Fatma Ulku; Torun, Dilek; Bolat, Filiz; Zumrutdal, Aysegul; Sezer, Siren; Ozdemir, Fatma Nurhan

2006-02-01

The most common form of renal involvement in Sjögren's syndrome (SS) is tubulointerstitial nephritis. Renal dysfunction is usually mild and subclinical. Glomerulonephritis (GMN) is rare in patients with SS. We report a 28-year-old multigravida patient with primary Sjögren's syndrome (pSS) and associated manifestations, who presented with acute renal failure in the 20th week of her fifth pregnancy. The complaints and clinical findings, positive Schirmer's test, findings of dry eye on ophthalmologic examination, and the salivary gland biopsy were compatible with SS. The patient exhibited no other clinical or laboratory findings indicative of other collagenous disease and/or rheumatoid arthritis. She refused renal biopsy, hesitating for fear of fetal loss; thus, based on the clinical and laboratory findings indicating rapidly progressive GMN and vasculitis, prednisolone, plasmapheresis, and one dose of cyclophosphamide were administered during the pregnancy. Hemodialysis five times weekly was performed. At the 28th week of gestation, she underwent a cesarean section due to early rupture of membranes and fetal distress. A healthy male boy was delivered. The renal biopsy performed 2 weeks after labor revealed mesangial proliferative glomerulonephritis. After the fourth cyclophosphamide treatment, her urinary output increased and she was discharged from the hemodialysis program. She remains in follow-up at our outpatient clinic free of hemodialysis for 4 months. This is the first report of mesangial proliferative GMN requiring dialysis in a pregnant pSS patient that has featured good maternal and fetal outcomes.

Cardiac MRI in pulmonary artery hypertension: correlations between morphological and functional parameters and invasive measurements

Energy Technology Data Exchange (ETDEWEB)

Alunni, Jean-Philippe; Otal, Philippe; Rousseau, Herve; Chabbert, Valerie [CHU Rangueil, Department of Radiology, Toulouse (France); Degano, Bruno; Tetu, Laurent; Didier, Alain [CHU Larrey, Department of Pneumology, Toulouse (France); Arnaud, Catherine [CHU Rangueil, Department of Methods in Clinical Research, Toulouse (France); Blot-Souletie, Nathalie [CHU Rangueil, Department of Cardiology, Toulouse (France)

2010-05-15

To compare cardiac MRI with right heart catheterisation in patients with pulmonary hypertension (PH) and to evaluate its ability to assess PH severity. Forty patients were included. MRI included cine and phase-contrast sequences, study of ventricular function, cardiac cavity areas and ratios, position of the interventricular septum (IVS) in systole and diastole, and flow measurements. We defined four groups according to the severity of PH and three groups according to IVS position: A, normal position; B, abnormal in diastole; C, abnormal in diastole and systole. IVS position was correlated with pulmonary artery pressures and PVR (pulmonary vascular resistance). Median pulmonary artery pressures and resistance were significantly higher in patients with an abnormal septal position compared with those with a normal position. Correlations were good between the right ventricular ejection fraction and PVR, right ventricular end-systolic volume and PAP, percentage of right ventricular area change and PVR, and diastolic and systolic ventricular area ratio and PVR. These parameters were significantly associated with PH severity. Cardiac MRI can help to assess the severity of PH. (orig.)

High pulmonary vascular resistance in addition to low right ventricular stroke work index effectively predicts biventricular assist device requirement.

Science.gov (United States)

Imamura, Teruhiko; Kinugawa, Koichiro; Kinoshita, Osamu; Nawata, Kan; Ono, Minoru

2016-03-01

Although the right ventricular stroke work index (RVSWI) is a good index for RV function, a low RVSWI is not necessarily an indicator for the need for a right ventricular assist device at the time of left VAD implantation. We here aimed to determine a more precise indicator for the need for a biventricular assist device (BiVAD). In total, 116 patients (mean age, 38 ± 14 years), who underwent hemodynamic assessments preoperatively including 12 BiVAD patients, and had been followed at our institute from 2003 to 2015, were included. Multivariate logistic regression analysis indicated that RVSWI and pulmonary vascular resistance (PVR) were independent predictors of BiVAD requirement (P 5 g/m, PVR 5, PVR > 3.7), (3) RV failure (RVSWI 3.7), and examined. Most of the patients in Group 4 (75 %), with acutely depressed hemodynamics and inflammatory responses in the myocardium, required BiVAD. Overall, patients with BiVAD had a worse survival rate as compared with those with LVAD alone. In conclusion, high PVR in addition to low RVSWI effectively predicts BiVAD requirement.

Role of P-glycoprotein on CD69+CD4+ cells in the pathogenesis of proliferative lupus nephritis and non-responsiveness to immunosuppressive therapy.

Science.gov (United States)

Tsujimura, Shizuyo; Adachi, Tomoko; Saito, Kazuyoshi; Tanaka, Yoshiya

2017-01-01

P-glycoprotein (P-gp) expression on activated lymphocytes in systemic lupus erythematosus (SLE) plays a role in active efflux of intracellular drugs, resulting in drug resistance. The role of P-gp-expressing lymphocytes in the pathogenesis of SLE remains unclear. The aim of this study was to determine the importance of P-gp + CD4 + cells in organ manifestations in refractory SLE. The proportion of P-gp + CD4 + cells was determined by flow cytometry in peripheral blood of patients with SLE (n=116) and healthy adults (n=10). Renal biopsy specimens were examined by immunohistochemistry for P-gp expression. CD69 is a marker of CD4 cell activation. The proportion of both P-gp-expressing CD4 + cells and CD69-expressing CD4 + cells in peripheral blood was higher in SLE than control. The proportion of P-gp + CD69 + CD4 + cells correlated with Systemic Lupus Erythematosus Disease Activity Index and was higher in poor responders to corticosteroids. Furthermore, the proportion of P-gp + CD69 + CD4 + cells was significantly higher in proliferative lupus nephritis (LN) with poor response to corticosteroids. The efficacy of immunosuppressive therapy depended on the regulation of the proportion of P-gp + CD69 + CD4 + cells. Marked accumulation of P-gp + CD4 + cells in renal interstitial tissue and high proportion of peripheral P-gp + CD69 + CD4 + cells were noted in patients with proliferative LN. The results showed high proportion of P-gp + CD69 + CD4 + cells in peripheral blood and their accumulation in renal tissue in patients with proliferative LN refractory to CS therapy, suggesting that P-gp expression on activated CD4 + T cells is a potentially useful marker for refractoriness to treatment and a novel target for treatment.

Anti-proliferative effect of 20-hydroxyecdysone in a lepidopteran cell line.

Science.gov (United States)

Auzoux-Bordenave, Stéphanie; Hatt, Philippe-Jacques; Porcheron, Patrick

2002-02-01

Ecdysteroids are steroid hormones involved in the epidermal growth of arthropods, controlling cell proliferation and further differentiation of target cells. The epidermal cell line IAL-PID2, established from imaginal discs of the Indian meal moth Plodia interpunctella kept its sensitivity to ecdysteroids in vitro, cells being able to respond to them by cytological and biochemical changes. When added to the culture medium, 20-hydroxyecdysone (20E) stopped cell proliferation and induced formation of epithelial-like aggregates. In order to better understand the cellular sequence of ecdysteroids signalling in epidermal cells we used the IAL-PID2 cell line for in vitro investigations of cytological events induced by the moulting hormone. After a 40 h serum deprivation, formazan assay (XTT) was routinely used to evaluate anti-proliferative effects of 20E during cell cycle. We established a more precise timing of the period of cell sensitivity to the hormone during the cell cycle, by the use of the mitotic index and the BrdU incorporation test. These in vitro assays were performed in parallel with the description of some hormone dependant cytological events, using immunofluorescent labelling with anti-beta tubulin/FITC antibodies and DNA staining.

An APC:WNT Counter-Current-Like Mechanism Regulates Cell Division Along the Human Colonic Crypt Axis: A Mechanism That Explains How APC Mutations Induce Proliferative Abnormalities That Drive Colon Cancer Development

Science.gov (United States)

Boman, Bruce M.; Fields, Jeremy Z.

2013-01-01

APC normally down-regulates WNT signaling in human colon, and APC mutations cause proliferative abnormalities in premalignant crypts leading to colon cancer, but the mechanisms are unclear at the level of spatial and functional organization of the crypt. Accordingly, we postulated a counter-current-like mechanism based on gradients of factors (APC;WNT) that regulate colonocyte proliferation along the crypt axis. During crypt renewal, stem cells (SCs) at the crypt bottom generate non-SC daughter cells that proliferate and differentiate while migrating upwards. The APC concentration is low at the crypt bottom and high at the top (where differentiated cells reside). WNT signaling, in contrast, is high at the bottom (where SCs reside) and low at the top. Given that WNT and APC gradients are counter to one another, we hypothesized that a counter-current-like mechanism exists. Since both APC and WNT signaling components (e.g., survivin) are required for mitosis, this mechanism establishes a zone in the lower crypt where conditions are optimal for maximal cell division and mitosis orientation (symmetric versus asymmetric). APC haploinsufficiency diminishes the APC gradient, shifts the proliferative zone upwards, and increases symmetric division, which causes SC overpopulation. In homozygote mutant crypts, these changes are exacerbated. Thus, APC-mutation-induced changes in the counter-current-like mechanism cause expansion of proliferative populations (SCs, rapidly proliferating cells) during tumorigenesis. We propose this mechanism also drives crypt fission, functions in the crypt cycle, and underlies adenoma development. Novel chemoprevention approaches designed to normalize the two gradients and readjust the proliferative zone downwards, might thwart progression of these premalignant changes. PMID:24224156

Retinal vascular abnormalities and dragged maculae in a carrier with a new NDP mutation (c.268delC) that caused severe Norrie disease in the proband.

Science.gov (United States)

Lin, Phoebe; Shankar, Suma P; Duncan, Jacque; Slavotinek, Anne; Stone, Edwin M; Rutar, Tina

2010-02-01

Norrie disease (ND) is caused by mutations in the ND pseudoglioma (NDP) gene (MIM 300658) located at chromosome Xp11.4-p11.3. ND is characterized by abnormal retinal vascular development and vitreoretinal disorganization presenting at birth. Systemic manifestations include sensorineural deafness, progressive mental disorder, behavioral and psychological problems, growth failure, and seizures. Other vitreoretinopathies that are associated with NDP gene mutations include X-linked familial exudative vitreoretinopathy, Coats disease, persistent fetal vasculature, and retinopathy of prematurity. Phenotypic variability associated with NDP gene mutations has been well documented in affected male patients. However, there are limited data on signs in female carriers, with mild peripheral retinal abnormalities reported in both carrier and noncarrier females of families with NDP gene mutations. Here, we report a family harboring a single base-pair deletion, c.268delC, in the NDP gene causing a severe ND phenotype in the male proband and peripheral retinal vascular abnormalities with dragged maculae similar to those observed in familial exudative vitreoretinopathy in his carrier mother. Copyright (c) 2010 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.

A new CT-score as index of hemodynamic changes in patients with chronic thromboembolic pulmonary hypertension.

Science.gov (United States)

Leone, Maria Barbara; Giannotta, Marica; Palazzini, Massimiliano; Cefarelli, Mariano; Martìn Suàrez, Sofia; Gotti, Enrico; Bacchi Reggiani, Maria Letizia; Zompatori, Maurizio; Galiè, Nazzareno

2017-07-01

The aim of this study was to retrospectively assess the relationship between radiological and hemodynamic parameters in patients with chronic thromboembolic pulmonary hypertension (CTEPH). We introduced a new CT-score to evaluate hemodynamic changes, only employing CT-pulmonary angiography (CTPA). 145 patients affected by CTEPH underwent hemodynamic and CTPA evaluation. Among these 145 patients, 69 underwent pulmonary endarterectomy (PEA) and performed a CTPA evaluation even after surgery. Hemodynamic assessment considered the values of mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR), obtained through right heart catheterization (RHC). Radiological evaluation included CTPA signs of pulmonary hypertension. A highly significant statistical correlation was observed between the new CT-score and both mPAP and PVR (p < 0.000) in the whole sample and also in the subgroup who underwent PEA. In addition, mPAP and PVR showed an important association with the severity of mosaic perfusion (p < 0.000). mPAP also correlated with main pulmonary artery diameter (p < 0.01); a significant association was found in both between PVR and tricuspid regurgitation(p < 0.000) and with PVR and presence of unilateral or bilateral pulmonary thromboembolic occlusion (p < 0.05). Our results confirm the diagnostic role of CTPA in evaluating patients with CTEPH and in addition open a new horizon in assessing hemodynamic changes in patients with CTEPH, only employing a CTPA, especially when RHC is contraindicated or not possible.

The prognostic value of oncogenic antigen 519 (OA-519) expression and proliferative activity detected by antibody MIB-1 in node-negative breast cancer

DEFF Research Database (Denmark)

Jensen, V; Ladekarl, M; Holm-Nielsen, P

1995-01-01

of invasion of skin or deep fascia (= T1N0M0 and T2N0M0). The median follow-up time was 104 months (range 5-143 months). Immunohistochemical analysis of OA-519 expression was performed on formalin-fixed, paraffin-embedded tissue. The proliferative activity was estimated using a Ki-67 equivalent monoclonal...

Intraretinal proliferation induced by retinal detachment

International Nuclear Information System (INIS)

Fisher, S.K.; Erickson, P.A.; Lewis, G.P.; Anderson, D.H.

1991-01-01

Cellular proliferation after retinal detachment was studied by 3 H-thymidine light microscopic autoradiography in cats that had experimental detachments of 0.5-180 days duration. The animals underwent labeling 2 hr before death with an intraocular injection of 200 microCi of 3 H-thymidine. The number of labeled nuclei were counted in 1-micron thick tissue sections in regions of detachment, in regions of the experimental eyes that remained attached, and in control eyes that had no detachments. In the normal eye, in one that had only the lens and vitreous removed, and in the eyes with 0.5- and 1-day detachments, the number of labeled nuclei ranged from 0/mm (0.5-day detachment) to 0.38/mm (lens and vitreous removed only). By 2 days postdetachment, the number of labeled nuclei increased to 2.09/mm. The highest levels of labeling occurred in two animals with detachments of 3 (7.86/mm) and 4 (7.09/mm) days. Thereafter, the numbers declined steadily until near-baseline counts were obtained at 14 days. The number of labeled nuclei was slightly elevated in the attached regions of two animals with 3-day detachments. Labeled cell types included: Mueller cells, astrocytes, pericytes, and endothelial cells of the retinal vasculature, and both resident (microglial cells) and invading macrophages. In an earlier study RPE cells were also shown to proliferate in response to detachment. Thus, these data show that proliferation is a rapid response to detachment, reaching a maximum within 4 days, and that virtually every nonneuronal cell type in the retina can participate in this response. The data suggest that events leading to such clinical manifestations as proliferative vitreoretinopathy and subretinal fibrosis may have their beginnings in this very early proliferative response

Proliferative responses in the local lymph node assay associated with concomitant exposure to 1,4-phenylenediamine and methyldibromo glutaronitrile: evidence for synergy?

Science.gov (United States)

Jowsey, Ian R; Basketter, David A; Irwin, Anita

2008-08-01

A key consideration when undertaking risk assessments should be the potential for synergy between contact allergens. Previously, this concept has only been investigated during elicitation in contact allergic individuals. To determine whether there exists evidence for synergy between contact allergens during the induction phase of skin sensitization using the mouse local lymph node assay (LLNA) as a model system. Proliferative responses in draining lymph nodes were assessed with increasing concentrations of 1,4-phenylenediamine (PPD), methyldibromo glutaronitrile (MDBGN), and a combination of PPD and MDBGN. Data from each of two independent experiments show that lymph node cell proliferation associated with combined exposure to PPD and MDBGN was, in general, only modestly increased relative to that predicted from a simple summation of their individual responses. Although the increase in response is very modest, it does imply a relationship between this combination of sensitizers that may not be simply additive in terms of their ability to stimulate proliferative responses in draining lymph nodes. The reproducibility of this observation should be confirmed in future studies with additional pairs of contact allergens to ascertain whether or not this represents evidence of synergy.

Gene Expression of IGF1, IGF1R, and IGFBP3 in Epiretinal Membranes of Patients with Proliferative Diabetic Retinopathy: Preliminary Study

Directory of Open Access Journals (Sweden)

Dorota Romaniuk

2013-01-01

Full Text Available The molecular mechanism formation of secondary epiretinal membranes (ERMs after proliferative diabetic retinopathy (PDR or primary idiopathic ERMs is still poorly understood. Therefore, the present study focused on the assessment of IGF1, IGF1R, and IGFBP3 mRNA levels in ERMs and PBMCs from patients with PDR. The examined group comprised 6 patients with secondary ERMs after PDR and the control group consisted of 11 patients with idiopathic ERMs. Quantification of IGF1, IGF1R, and IGFBP3 mRNAs was performed by real-time QRT-PCR technique. In ERMs, IGF1 and IGF1R mRNA levels were significantly higher in patients with diabetes compared to control subjects. In PBMCs, there were no statistically significant differences of IGF1, IGF1R, and IGFBP3 expression between diabetic and nondiabetic patients. In conclusion, our study indicated IGF1 and IGF1R differential expression in ERMs, but not in PBMCs, of diabetic and nondiabetic patients, suggesting that these factors can be involved in the pathogenesis or progression of proliferative vitreoretinal disorders. This trial is registered with NCT00841334.

A lentiviral vector with expression controlled by E2F-1: A potential tool for the study and treatment of proliferative diseases

International Nuclear Information System (INIS)

Strauss, Bryan E.; Patricio, Juliana Rotelli; Vieira de Carvalho, Anna Carolina; Bajgelman, Marcio C.

2006-01-01

We have constructed a lentiviral vector with expression limited to cells presenting active E2F-1 protein, a potential advantage for gene therapy of proliferative diseases. For the FE2FLW vector, the promoter region of the human E2F-1 gene was utilized to drive expression of luciferase cDNA, included as a reporter of viral expression. Primary, immortalized, and transformed cells were transduced with the FE2FLW vector and cell cycle alterations were induced with serum starvation/replacement, contact inhibition or drug treatment, revealing cell cycle-dependent changes in reporter activity. Forced E2F-1 expression, but not E2F-2 or E2F-3, increased reporter activity, indicating a major role for this factor in controlling expression from the FE2FLW virus. We show the utility of this vector as a reporter of E2F-1 and proliferation-dependent cellular alterations upon cytotoxic/cytostatic treatment, such as the introduction of tumor suppressor genes. We propose that the FE2FLW vector may be a starting point for the development of gene therapy strategies for proliferative diseases, such as cancer or restinosis

Comparative Study of Green Sub- and Supercritical Processes to Obtain Carnosic Acid and Carnosol-Enriched Rosemary Extracts with in Vitro Anti-Proliferative Activity on Colon Cancer Cells

Directory of Open Access Journals (Sweden)

Andrea del Pilar Sánchez-Camargo

2016-12-01

Full Text Available In the present work, four green processes have been compared to evaluate their potential to obtain rosemary extracts with in vitro anti-proliferative activity against two colon cancer cell lines (HT-29 and HCT116. The processes, carried out under optimal conditions, were: (1 pressurized liquid extraction (PLE, using an hydroalcoholic mixture as solvent at lab-scale; (2 Single-step supercritical fluid extraction (SFE at pilot scale; (3 Intensified two-step sequential SFE at pilot scale; (4 Integrated PLE plus supercritical antisolvent fractionation (SAF at pilot scale. Although higher extraction yields were achieved by using PLE (38.46% dry weight, this extract provided the lowest anti-proliferative activity with no observed cytotoxic effects at the assayed concentrations. On the other hand, extracts obtained using the PLE + SAF process provided the most active rosemary extracts against both colon cancer cell lines, with LC50 ranging from 11.2 to 12.4 µg/mL and from 21.8 to 31.9 µg/mL for HCT116 and HT-29, respectively. In general, active rosemary extracts were characterized by containing carnosic acid (CA and carnosol (CS at concentrations above 263.7 and 33.9 mg/g extract, respectively. Some distinct compounds have been identified in the SAF extracts (rosmaridiphenol and safficinolide, suggesting their possible role as additional contributors to the observed strong anti-proliferative activity of CA and CS in SAF extracts.

Is Smoking a Risk Factor for Proliferative Diabetic Retinopathy in Type 1 Diabetes?

DEFF Research Database (Denmark)

Gaedt Thorlund, Mie; Borg Madsen, Mette; Green, Anders

2013-01-01

were asked about their smoking habits. The level of retinopathy was evaluated by ophthalmoscopy at baseline and by nine 45-degree colour field fundus photos at the follow-up. Results: In multivariate analyses there was a trend that current smokers at baseline were more likely to develop PDR......Aim: The aim was to evaluate if smoking was a risk factor for proliferative retinopathy (PDR) in a 25-year follow-up study. Methods: 201 persons from a population-based cohort of Danish type 1 diabetic patients were examined at baseline and again 25 years later. At both examinations the patients...... at the follow-up (odds ratio 1.90, 95% confidence interval 0.88-4.11, p = 0.10). Neither smoking status at the follow-up nor pack-years of smoking were associated with PDR. Conclusions: We found neither a beneficial nor a harmful effect of smoking on long-term incidence. Selective mortality among smokers...

Radiation retinopathy as an experimental model for ischemic proliferative retinopathy and rubeosis iridis

International Nuclear Information System (INIS)

Irvine, A.R.; Wood, I.S.

1987-01-01

We produced radiation retinopathy in capuchin monkeys and studied them with fluorescein angiography and light and electron microscopy. The animals were followed up from ten days to 3 1/2 years after radiation in order to determine whether this could provide an experimental model for other chronic ischemic-proliferative retinopathies, such as diabetes. The first change detected after radiation was the focal loss of capillary endothelial cells and pericytes. As the areas of acellular capillaries became confluent, cotton-wool spots became visible ophthalmoscopically. These increased in number and then faded away, leaving large areas of retinal capillary perfusion. Histologic studies showed occlusion first of the deeper, smaller retinal vessels and then gradually of the larger vessels. Intraretinal neovascularization as well as apparent recanalization then developed, but no new vessels extended through the internal limiting lamina into the vitreous. Rubeosis iridis with neovascular glaucoma developed 2 1/2 to 3 1/2 years postirradiation, and vitreous aspirate demonstrated a high level of angiogenic factor

Tenascin-C in the extracellular matrix promotes the selection of highly proliferative and tubulogenesis-defective endothelial cells

Energy Technology Data Exchange (ETDEWEB)

Alves, Tercia Rodrigues [Universidade do Estado do Rio de Janeiro (UERJ), Instituto de Biologia Roberto Alcantara Gomes, Departamento de Biologia Celular, Laboratorio de Biologia da Celula Endotelial e da Angiogenese (LabAngio), Rio de Janeiro (Brazil); Universidade Federal do Rio de Janeiro (UFRJ), Programa de Biologia Celular e do Desenvolvimento, Instituto de Ciencias Biomedicas, INNT/INCT/MCT, Rio de Janeiro (Brazil); Carvalho da Fonseca, Anna Carolina [Universidade Federal do Rio de Janeiro (UFRJ), Programa de Biologia Celular e do Desenvolvimento, Instituto de Ciencias Biomedicas, INNT/INCT/MCT, Rio de Janeiro (Brazil); Nunes, Sara Santana; Oliveira da Silva, Aline [Universidade do Estado do Rio de Janeiro (UERJ), Instituto de Biologia Roberto Alcantara Gomes, Departamento de Biologia Celular, Laboratorio de Biologia da Celula Endotelial e da Angiogenese (LabAngio), Rio de Janeiro (Brazil); Dubois, Luiz Gustavo Feijo; Faria, Jane; Kahn, Suzana Assad [Universidade Federal do Rio de Janeiro (UFRJ), Programa de Biologia Celular e do Desenvolvimento, Instituto de Ciencias Biomedicas, INNT/INCT/MCT, Rio de Janeiro (Brazil); Viana, Nathan Bessa [Universidade Federal do Rio de Janeiro, Laboratorio de Pincas Oticas, Coordenacao de Programas de Estudos Avancados, Instituto de Ciencias Biomedicas, Rio de Janeiro (Brazil); Universidade Federal do Rio de Janeiro, Instituto de Fisica, Rio de Janeiro (Brazil); Marcondes, Jorge [Universidade Federal do Rio de Janeiro, Hospital Universitario Clementino Fraga Filho, Servico de Neurocirurgia, Rio de Janeiro (Brazil); Legrand, Chantal [Institut Universitaire d' Hematologie, Universite Paris-Diderot, Paris 7, INSERM U553, Paris (France); Moura-Neto, Vivaldo [Universidade Federal do Rio de Janeiro (UFRJ), Programa de Biologia Celular e do Desenvolvimento, Instituto de Ciencias Biomedicas, INNT/INCT/MCT, Rio de Janeiro (Brazil); and others

2011-09-10

The extracellular matrix (ECM) contains important cues for tissue homeostasis and morphogenesis. The matricellular protein tenascin-C (TN-C) is overexpressed in remodeling tissues and cancer. In the present work, we studied the effect of different ECM-which exhibited a significant diversity in their TN-C content-in endothelial survival, proliferation and tubulogenic differentiation: autologous (endothelial) ECM devoid of TN-C, but bearing large amounts of FN; fibroblast ECM, bearing both high TN-C and FN contents; and finally, glioma-derived matrices, usually poor in FN, but very rich in TN-C. HUVECs initially adhered to the immobilized matrix produced by U373 MG glioma cells, but significantly detached and died by anoikis (50 to 80%) after 24 h, as compared with cells incubated with endothelial and fibroblast matrices. Surviving endothelial cells (20 to 50%) became up to 6-fold more proliferative and formed 74-97% less tube-like structures in vitro than cells grown on non-tumoral matrices. An antibody against the EGF-like repeats of tenascin-C (TN-C) partially rescued cells from the tubulogenic defect, indicating that this molecule is responsible for the selection of highly proliferative and tubulogenic defective endothelial cells. Interestingly, by using defined substrata, in conditions that mimic glioma and normal cell ECM composition, we observed that fibronectin (FN) modulates the TN-C-induced selection of endothelial cells. Our data show that TN-C is able to modulate endothelial branching morphogenesis in vitro and, since it is prevalent in matrices of injured and tumor tissues, also suggest a role for this protein in vascular morphogenesis, in these physiological contexts.

Tenascin-C in the extracellular matrix promotes the selection of highly proliferative and tubulogenesis-defective endothelial cells

International Nuclear Information System (INIS)

Alves, Tercia Rodrigues; Carvalho da Fonseca, Anna Carolina; Nunes, Sara Santana; Oliveira da Silva, Aline; Dubois, Luiz Gustavo Feijo; Faria, Jane; Kahn, Suzana Assad; Viana, Nathan Bessa; Marcondes, Jorge; Legrand, Chantal; Moura-Neto, Vivaldo

2011-01-01

The extracellular matrix (ECM) contains important cues for tissue homeostasis and morphogenesis. The matricellular protein tenascin-C (TN-C) is overexpressed in remodeling tissues and cancer. In the present work, we studied the effect of different ECM-which exhibited a significant diversity in their TN-C content-in endothelial survival, proliferation and tubulogenic differentiation: autologous (endothelial) ECM devoid of TN-C, but bearing large amounts of FN; fibroblast ECM, bearing both high TN-C and FN contents; and finally, glioma-derived matrices, usually poor in FN, but very rich in TN-C. HUVECs initially adhered to the immobilized matrix produced by U373 MG glioma cells, but significantly detached and died by anoikis (50 to 80%) after 24 h, as compared with cells incubated with endothelial and fibroblast matrices. Surviving endothelial cells (20 to 50%) became up to 6-fold more proliferative and formed 74-97% less tube-like structures in vitro than cells grown on non-tumoral matrices. An antibody against the EGF-like repeats of tenascin-C (TN-C) partially rescued cells from the tubulogenic defect, indicating that this molecule is responsible for the selection of highly proliferative and tubulogenic defective endothelial cells. Interestingly, by using defined substrata, in conditions that mimic glioma and normal cell ECM composition, we observed that fibronectin (FN) modulates the TN-C-induced selection of endothelial cells. Our data show that TN-C is able to modulate endothelial branching morphogenesis in vitro and, since it is prevalent in matrices of injured and tumor tissues, also suggest a role for this protein in vascular morphogenesis, in these physiological contexts.

Glomerular Damage in Experimental Proliferative Glomerulonephritis Under Glomerular Capillary Hypertension

Directory of Open Access Journals (Sweden)

Pei-Rong Wang

2015-03-01

Full Text Available Background/Aims: Immunologically and hemodynamically mediated the destruction of glomerular architecture is thought to be the major causes of end-stage renal failure. The purpose of this study is to evaluate the effect of glomerular hypertension on glomerular injury and the progression of glomerular sclerosis after Thy-1 nephritis was induced. Method: Thy-1 nephritis was induced in the stroke-prone spontaneously hypertensive rat strain (SHR-SP (group SP and in age-matched Wistar-Kyoto (WKY (group WKY rats, following unilateral nephrectomy (UNX, and a vehicle was injected alone in UNX SHR-SP as control (group SC. Result: The degree of glomerular damage in response to a single dose of anti-thy-1 antibody, and its functional consequences (eg. proteinuria, diminished GFR are more pronounced in group SP than normotensive group WKY and hypertensive group SC without mesangial cell injury. While normotensive group WKY rats recovered completely from mesangial cell injury on day 28-42, glomeruli in group SP kept on persistent macrophage infiltration, α-SMA expression on day 42-56. In addition, glomerular capillary repair with the GECs was rarely seen in pronouncedly proliferative and sclerostic areas. The incidence of glomerular sclerosis and the level of proteinuria were markedly increased by day 56 in the group SP. Conclusions: Our results demonstrate that glomerular hypertension aggravate glomerular damage and glomerulosclerosis in this model of Thy 1 nephritis.

Proliferative activity of vervet monkey bone marrow-derived adherent cells

International Nuclear Information System (INIS)

Kramvis, A.; Garnett, H.M.

1987-01-01

Vervet monkey bone marrow-derived adherent cell population cultured in Fischer's medium supplemented with 12.5% fetal calf serum and 12.5% horse serum consists of two cell shapes: fusiform (type I) and polygonal (type II). Limiting-dilution cloning of the cells suggested that the two morphologically distinct cell types belong to the same cellular system even though they differ in their proliferative capabilities. The labeling index of type II cells, as measured by autoradiography, was found to be consistently lower than that of type I cells. It is probable that these two phenotypes represent different stages of differentiation, where progenitor type I gives rise to type II cells. The bone marrow-derived adherent cells were found to be cytokinetically at rest in vivo, using the thymidine suicide test, and relatively radioresistant with a D0 = 2.1 Gy and n = 2.36 at the time of explantation from the bone. Furthermore, in culture these cells are characterized by a relatively long cell cycle of 60 h, where the length of the S phase is 30 h, G2 is 12 h, M is 6 h, and G1 is 12 h. Thus, the vervet monkey bone marrow-derived adherent cells represent a cell population with a low turnover rate both in vivo and in vitro

Clinical significance of MCM-2 and MCM-5 expression in colon cancer: association with clinicopathological parameters and tumor proliferative capacity.

Science.gov (United States)

Giaginis, Constantinos; Georgiadou, Maria; Dimakopoulou, Konstantina; Tsourouflis, Gerasimos; Gatzidou, Elisavet; Kouraklis, Gregorios; Theocharis, Stamatios

2009-02-01

Minichromosome maintenance (MCM) proteins are essential components of DNA replication, being related to cell proliferation, and serve as useful markers for cancer screening, surveillance, and prognosis. Our aim was to examine the clinical significance of MCM-2 and MCM-5 protein expression in colon cancer and to evaluate the association with various clinicopathological characteristics and tumor proliferative capacity. Immunohistochemical expression of MCM-2 and MCM-5 was performed on paraffin-embedded malignant tissue sections obtained from 96 patients with colon cancer. MCM-2 and MCM-5 expression was correlated with different clinicopathological characteristics, proliferative capacity (Ki-67 labeling index), and p53 cell-cycle regulator expression. MCM-2 and Ki-67 expression was significantly associated with the tumors' histological grade (P = 0.003), existence of nodular metastases (N) (P = 0.003 and P = 0.030, respectively), malignancy on adenoma (P = 0.029 and P = 0.024, respectively), and vascular invasion (P = 0.010 and P = 0.011, respectively). MCM-2 expression was additionally associated with Dukes' stage (P = 0.005). Significant positive relationships were found between the expression of MCM-2 or MCM-5 proteins and that of Ki-67 protein (r = 0.963, P-value characteristics examined. The current data suggest that MCM-2 protein expression is significantly associated with important clinicopathological characteristics for patients' management, being correlated with the cell proliferation state in colon cancer.

Neurotrophins and Neurotrophin Receptors in Proliferative Diabetic Retinopathy

Science.gov (United States)

Abu El-Asrar, Ahmed M.; Mohammad, Ghulam; De Hertogh, Gert; Nawaz, Mohd Imtiaz; Van Den Eynde, Kathleen; Siddiquei, Mohammad Mairaj; Struyf, Sofie; Opdenakker, Ghislain; Geboes, Karel

2013-01-01

Neurotrophins (NTs) are emerging as important mediators of angiogenesis and fibrosis. We investigated the expression of the NTs nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4) and their receptors TrkA, TrkB, and TrkC in proliferative diabetic retinopathy (PDR). As a comparison, we examined the expression of NTs and their receptors in the retinas of diabetic rats. Vitreous samples from 16 PDR and 15 nondiabetic patients were studied by Western blot analysis and enzyme-linked immunosorbent assay (ELISA). Epiretinal membranes from 17 patients with PDR were studied by immunohistochemistry. Rats were made diabetic with a single high dose of streptozotocin and retinas of rats were examined by Western blot analysis. Western blot analysis revealed a significant increase in the expression of NT-3 and NT-4 and the shedding of receptors TrkA and TrkB in vitreous samples from PDR patients compared to nondiabetic controls, whereas NGF and BDNF and the receptor TrkC were not detected with the use of Western blot analysis and ELISA. In epiretinal membranes, vascular endothelial cells and myofibroblasts expressed NT-3 and the receptors TrkA, TrkB and TrkC in situ, whereas NT-4 was not detected. The expression levels of NT-3 and NT-4 and the receptors TrkA and TrkB, both in intact and solubilized forms, were upregulated in the retinas of diabetic rats, whereas the receptor TrkC was not detected. Co-immunoprecipitation studies revealed binding between NT-3 and the receptors TrkA and TrkB in the retinas of diabetic rats. Our findings in diabetic eyes from humans and rats suggest that the increased expression levels within the NT-3 and NT-4/Trk axis are associated with the progression of PDR. PMID:23762379

Structural Changes of the Macula on Optical Coherence Tomography after Vitrectomy for Proliferative Diabetic Retinopathy.

Science.gov (United States)

Im, Jong Chan; Kim, Jong Ho; Park, Dong Ho; Shin, Jae Pil

2017-01-01

This study aimed to evaluate the relationship between macular structural changes and visual prognosis after pars plana vitrectomy (PPV) for proliferative diabetic retinopathy. The study included 60 eyes that had undergone PPV. Macular optical coherence tomography (OCT) findings were classified into 5 groups preoperatively and 10 groups postoperatively. Best-corrected visual acuity (BCVA) were analyzed according to pre- and postoperative OCT. From the preoperative OCT, normal fovea with/without traction, normal fovea with preretinal hemorrhage, and tractional retinal detachment involving fovea showed an increase in BCVA after PPV (all p 20/50). Subfoveal fibrosis, macular hole, loss of foveal depression, and serous foveal detachment showed poor visual prognosis (BCVA <20/100). Macular structural changes were various after PPV, and visual prognosis correlated with these changes. © 2017 S. Karger AG, Basel.

Origin of negative resistance in anion migration controlled resistive memory

Science.gov (United States)

Banerjee, Writam; Wu, Facai; Hu, Yuan; Wu, Quantan; Wu, Zuheng; Liu, Qi; Liu, Ming

2018-03-01

Resistive random access memory (RRAM) is one of the most promising emerging nonvolatile technologies for the futuristic memory devices. Resistive switching behavior often shows negative resistance (NR), either voltage controlled or current controlled. In this work, the origin of a current compliance dependent voltage controlled NR effect during the resetting of anion migration based RRAM devices is discussed. The N-type voltage controlled NR is a high field driven phenomena. The current conduction within the range of a certain negative voltage is mostly dominated by space charge limited current. But with the higher negative voltage, a field induced tunneling effect is generated in the NR region. The voltage controlled NR is strongly dependent on the compliance current. The area independent behavior indicates the filamentary switching. The peak to valley ratio (PVR) is > 5. The variation of PVR as a function of the conduction band offset is achieved. Compared to other reported works, based on the PVR, it is possible to distinguish the RRAM types. Generally, due to the higher electric field effect on the metallic bridge during RESET, the electrochemical metallization type RRAM shows much higher PVR than the valance change type RRAM.

XIAP and Ki-67: A Correlation Between Antiapoptotic and Proliferative Marker Expression in Benign and Malignant Tumours of Salivary Gland: An Immunohistochemical Study.

Science.gov (United States)

Bagulkar, Bhupesh Bhayyaji; Gawande, Madhuri; Chaudhary, Minal; Gadbail, Amol Ramchandra; Patil, Swati; Bagulkar, Smita

2015-02-01

Impaired balance between cell proliferation and apoptosis is crucial to the development of malignant neoplasm. The purpose of this study was to evaluate and compare the expression of X-Linked inhibitor of apoptotic protein (XIAP) (antiapoptotic marker) and Ki-67 (proliferative marker) expression in benign and malignant salivary gland (SG) tumours. The study consisted of 40 cases of benign SG tumours and 50 cases of malignant SG tumours. The immunohistochemistry was carried out by using Ki-67 antibody (clone MIB-1) and XIAP antibody in all the groups. XIAP expression was significantly higher in malignant SG tumours than benign SG tumours (p = 0.016). Ki-67 LI was significantly higher in malignant SG tumours than benign SG tumours (p = 0.0002). Statistically significant positive correlation between Ki-67 count and XIAP expression was noted in benign and malignant SG tumours (p = 0.000). As the expression of an antiapoptotic marker (XIAP) increases, the expression of a proliferative marker (Ki-67) also increases from benign to malignant SG tumours. Thus, targeted therapy of XIAP may play a future role in the management of SG malignancy.

Non-proliferative diabetic retinopathy symptoms detection and classification using neural network.

Science.gov (United States)

Al-Jarrah, Mohammad A; Shatnawi, Hadeel

2017-08-01

Diabetic retinopathy (DR) causes blindness in the working age for people with diabetes in most countries. The increasing number of people with diabetes worldwide suggests that DR will continue to be major contributors to vision loss. Early detection of retinopathy progress in individuals with diabetes is critical for preventing visual loss. Non-proliferative DR (NPDR) is an early stage of DR. Moreover, NPDR can be classified into mild, moderate and severe. This paper proposes a novel morphology-based algorithm for detecting retinal lesions and classifying each case. First, the proposed algorithm detects the three DR lesions, namely haemorrhages, microaneurysms and exudates. Second, we defined and extracted a set of features from detected lesions. The set of selected feature emulates what physicians looked for in classifying NPDR case. Finally, we designed an artificial neural network (ANN) classifier with three layers to classify NPDR to normal, mild, moderate and severe. Bayesian regularisation and resilient backpropagation algorithms are used to train ANN. The accuracy for the proposed classifiers based on Bayesian regularisation and resilient backpropagation algorithms are 96.6 and 89.9, respectively. The obtained results are compared with results of the recent published classifier. Our proposed classifier outperforms the best in terms of sensitivity and specificity.

Pulmonary stenosis and pulmonary regurgitation: both ends of the spectrum in residual hemodynamic impairment after tetralogy of Fallot repair

Science.gov (United States)

Park, Han Ki

2013-01-01

Repair of tetralogy of Fallot (TOF) has shown excellent outcomes. However it leaves varying degrees of residual hemodynamic impairment, with severe pulmonary stenosis (PS) and free pulmonary regurgitation (PR) at both ends of the spectrum. Since the 1980s, studies evaluating late outcomes after TOF repair revealed the adverse impacts of residual chronic PR on RV volume and function; thus, a turnaround of operational strategies has occurred from aggressive RV outflow tract (RVOT) reconstruction for complete relief of RVOT obstruction to conservative RVOT reconstruction for limiting PR. This transformation has raised the question of how much residual PS after conservative RVOT reconstruction is acceptable. Besides, as pulmonary valve replacement (PVR) increases in patients with RV deterioration from residual PR, there is concern regarding when it should be performed. Regarding residual PS, several studies revealed that PS in addition to PR was associated with less PR and a small RV volume. This suggests that PS combined with PR makes RV diastolic property to protect against dilatation through RV hypertrophy and supports conservative RVOT enlargement despite residual PS. Also, several studies have revealed the pre-PVR threshold of RV parameters for the normalization of RV volume and function after PVR, and based on these results, the indications for PVR have been revised. Although there is no established strategy, better understanding of RV mechanics, development of new surgical and interventional techniques, and evidence for the effect of PVR on RV reverse remodeling and its late outcome will aid us to optimize the management of TOF. PMID:23807889

Prognostic Value of Pulmonary Vascular Resistance by Magnetic Resonance in Systolic Heart Failure

Energy Technology Data Exchange (ETDEWEB)

Fabregat-Andrés, Óscar, E-mail: osfabregat@gmail.com [Departamento de Cardiologia - Hospital General Universitario de Valencia, Valencia (Spain); Fundación para la Investigación - Hospital General Universitario de Valencia, Valencia (Spain); Estornell-Erill, Jordi [Unidad de Imagen Cardiaca - ERESA - Hospital General Universitario de Valencia, Valencia (Spain); Ridocci-Soriano, Francisco [Departamento de Cardiologia - Hospital General Universitario de Valencia, Valencia (Spain); Departamento de Medicina. Universitat de Valencia, Valencia (Spain); Pérez-Boscá, José Leandro [Departamento de Cardiologia - Hospital General Universitario de Valencia, Valencia (Spain); García-González, Pilar [Unidad de Imagen Cardiaca - ERESA - Hospital General Universitario de Valencia, Valencia (Spain); Payá-Serrano, Rafael [Departamento de Cardiologia - Hospital General Universitario de Valencia, Valencia (Spain); Departamento de Medicina. Universitat de Valencia, Valencia (Spain); Morell, Salvador [Departamento de Cardiologia - Hospital General Universitario de Valencia, Valencia (Spain); Cortijo, Julio [Fundación para la Investigación - Hospital General Universitario de Valencia, Valencia (Spain); Departamento de Farmacologia. Universitat de Valencia, Valencia (Spain)

2016-03-15

Pulmonary hypertension is associated with poor prognosis in heart failure. However, non-invasive diagnosis is still challenging in clinical practice. We sought to assess the prognostic utility of non-invasive estimation of pulmonary vascular resistances (PVR) by cardiovascular magnetic resonance to predict adverse cardiovascular outcomes in heart failure with reduced ejection fraction (HFrEF). Prospective registry of patients with left ventricular ejection fraction (LVEF) < 40% and recently admitted for decompensated heart failure during three years. PVRwere calculated based on right ventricular ejection fraction and average velocity of the pulmonary artery estimated during cardiac magnetic resonance. Readmission for heart failure and all-cause mortality were considered as adverse events at follow-up. 105 patients (average LVEF 26.0 ±7.7%, ischemic etiology 43%) were included. Patients with adverse events at long-term follow-up had higher values of PVR (6.93 ± 1.9 vs. 4.6 ± 1.7estimated Wood Units (eWu), p < 0.001). In multivariate Cox regression analysis, PVR ≥ 5 eWu(cutoff value according to ROC curve) was independently associated with increased risk of adverse events at 9 months follow-up (HR2.98; 95% CI 1.12-7.88; p < 0.03). In patients with HFrEF, the presence of PVR ≥ 5.0 Wu is associated with significantly worse clinical outcome at follow-up. Non-invasive estimation of PVR by cardiac magnetic resonance might be useful for risk stratification in HFrEF, irrespective of etiology, presence of late gadolinium enhancement or LVEF.

Pulmonary stenosis and pulmonary regurgitation: both ends of the spectrum in residual hemodynamic impairment after tetralogy of Fallot repair.

Science.gov (United States)

Yoo, Byung Won; Park, Han Ki

2013-06-01

Repair of tetralogy of Fallot (TOF) has shown excellent outcomes. However it leaves varying degrees of residual hemodynamic impairment, with severe pulmonary stenosis (PS) and free pulmonary regurgitation (PR) at both ends of the spectrum. Since the 1980s, studies evaluating late outcomes after TOF repair revealed the adverse impacts of residual chronic PR on RV volume and function; thus, a turnaround of operational strategies has occurred from aggressive RV outflow tract (RVOT) reconstruction for complete relief of RVOT obstruction to conservative RVOT reconstruction for limiting PR. This transformation has raised the question of how much residual PS after conservative RVOT reconstruction is acceptable. Besides, as pulmonary valve replacement (PVR) increases in patients with RV deterioration from residual PR, there is concern regarding when it should be performed. Regarding residual PS, several studies revealed that PS in addition to PR was associated with less PR and a small RV volume. This suggests that PS combined with PR makes RV diastolic property to protect against dilatation through RV hypertrophy and supports conservative RVOT enlargement despite residual PS. Also, several studies have revealed the pre-PVR threshold of RV parameters for the normalization of RV volume and function after PVR, and based on these results, the indications for PVR have been revised. Although there is no established strategy, better understanding of RV mechanics, development of new surgical and interventional techniques, and evidence for the effect of PVR on RV reverse remodeling and its late outcome will aid us to optimize the management of TOF.

Pulmonary stenosis and pulmonary regurgitation: both ends of the spectrum in residual hemodynamic impairment after tetralogy of Fallot repair

Directory of Open Access Journals (Sweden)

Byung Won Yoo

2013-06-01

Full Text Available Repair of tetralogy of Fallot (TOF has shown excellent outcomes. However it leaves varying degrees of residual hemodynamic impairment, with severe pulmonary stenosis (PS and free pulmonary regurgitation (PR at both ends of the spectrum. Since the 1980s, studies evaluating late outcomes after TOF repair revealed the adverse impacts of residual chronic PR on RV volume and function; thus, a turnaround of operational strategies has occurred from aggressive RV outflow tract (RVOT reconstruction for complete relief of RVOT obstruction to conservative RVOT reconstruction for limiting PR. This transformation has raised the question of how much residual PS after conservative RVOT reconstruction is acceptable. Besides, as pulmonary valve replacement (PVR increases in patients with RV deterioration from residual PR, there is concern regarding when it should be performed. Regarding residual PS, several studies revealed that PS in addition to PR was associated with less PR and a small RV volume. This suggests that PS combined with PR makes RV diastolic property to protect against dilatation through RV hypertrophy and supports conservative RVOT enlargement despite residual PS. Also, several studies have revealed the pre-PVR threshold of RV parameters for the normalization of RV volume and function after PVR, and based on these results, the indications for PVR have been revised. Although there is no established strategy, better understanding of RV mechanics, development of new surgical and interventional techniques, and evidence for the effect of PVR on RV reverse remodeling and its late outcome will aid us to optimize the management of TOF.

Prognostic Value of Pulmonary Vascular Resistance by Magnetic Resonance in Systolic Heart Failure

International Nuclear Information System (INIS)

Fabregat-Andrés, Óscar; Estornell-Erill, Jordi; Ridocci-Soriano, Francisco; Pérez-Boscá, José Leandro; García-González, Pilar; Payá-Serrano, Rafael; Morell, Salvador; Cortijo, Julio

2016-01-01

Pulmonary hypertension is associated with poor prognosis in heart failure. However, non-invasive diagnosis is still challenging in clinical practice. We sought to assess the prognostic utility of non-invasive estimation of pulmonary vascular resistances (PVR) by cardiovascular magnetic resonance to predict adverse cardiovascular outcomes in heart failure with reduced ejection fraction (HFrEF). Prospective registry of patients with left ventricular ejection fraction (LVEF) < 40% and recently admitted for decompensated heart failure during three years. PVRwere calculated based on right ventricular ejection fraction and average velocity of the pulmonary artery estimated during cardiac magnetic resonance. Readmission for heart failure and all-cause mortality were considered as adverse events at follow-up. 105 patients (average LVEF 26.0 ±7.7%, ischemic etiology 43%) were included. Patients with adverse events at long-term follow-up had higher values of PVR (6.93 ± 1.9 vs. 4.6 ± 1.7estimated Wood Units (eWu), p < 0.001). In multivariate Cox regression analysis, PVR ≥ 5 eWu(cutoff value according to ROC curve) was independently associated with increased risk of adverse events at 9 months follow-up (HR2.98; 95% CI 1.12-7.88; p < 0.03). In patients with HFrEF, the presence of PVR ≥ 5.0 Wu is associated with significantly worse clinical outcome at follow-up. Non-invasive estimation of PVR by cardiac magnetic resonance might be useful for risk stratification in HFrEF, irrespective of etiology, presence of late gadolinium enhancement or LVEF

"Pulmonary valve replacement diminishes the presence of restrictive physiology and reduces atrial volumes": a prospective study in Tetralogy of Fallot patients.

Science.gov (United States)

Pijuan-Domenech, Antonia; Pineda, Victor; Castro, Miguel Angel; Sureda-Barbosa, Carlos; Ribera, Aida; Cruz, Luz M; Ferreira-Gonzalez, Ignacio; Dos-Subirà, Laura; Subirana-Domènech, Teresa; Garcia-Dorado, David; Casaldàliga-Ferrer, Jaume

2014-11-15

Pulmonary valve replacement (PVR) reduces right ventricular (RV) volumes in the setting of long-term pulmonary regurgitation after Tetralogy of Fallot (ToF) repair; however, little is known of its effect on RV diastolic function. Right atrial volumes may reflect the burden of RV diastolic dysfunction. The objective of this paper is to evaluate the clinical, echocardiographic, biochemical and cardiac magnetic resonance (CMR) variables, focusing particularly on right atrial response and right ventricular diastolic function prior to and after elective PVR in adult patients with ToF. This prospective study was conducted from January 2009 to April 2013 in consecutive patients > 18 years of age who had undergone ToF repair in childhood and were accepted for elective PVR. Twenty patients (mean age: 35 years; 70% men) agreed to enter the study. PVR was performed with a bioporcine prosthesis. Concomitant RV reduction was performed in all cases when technically possible. Pulmonary end-diastolic forward flow (EDFF) decreased significantly from 5.4 ml/m(2) to 0.3 ml/m(2) (p volumes by 25% (p = 0.0024): mean indexed diastolic/systolic atrial volumes prior to surgery were 43 ml/m(2) (SD+/-4.6)/63 ml/m(2) (SD+/-5.5), and dropped to 33 ml/m(2) (SD+/-3)/46 ml/m(2) (SD+/-2.55) post-surgery. All patients presented right ventricular diastolic and systolic volume reductions, with a mean volume reduction of 35% (p volumes in keeping with the known reduction in RV volumes, after PVR. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Exercise capacity in the Bidirectional Glenn physiology: Coupling cardiac index, ventricular function and oxygen extraction ratio.

Science.gov (United States)

Vallecilla, Carolina; Khiabani, Reza H; Trusty, Phillip; Sandoval, Néstor; Fogel, Mark; Briceño, Juan Carlos; Yoganathan, Ajit P

2015-07-16

In Bi-directional Glenn (BDG) physiology, the superior systemic circulation and pulmonary circulation are in series. Consequently, only blood from the superior vena cava is oxygenated in the lungs. Oxygenated blood then travels to the ventricle where it is mixed with blood returning from the lower body. Therefore, incremental changes in oxygen extraction ratio (OER) could compromise exercise tolerance. In this study, the effect of exercise on the hemodynamic and ventricular performance of BDG physiology was investigated using clinical patient data as inputs for a lumped parameter model coupled with oxygenation equations. Changes in cardiac index, Qp/Qs, systemic pressure, oxygen extraction ratio and ventricular/vascular coupling ratio were calculated for three different exercise levels. The patient cohort (n=29) was sub-grouped by age and pulmonary vascular resistance (PVR) at rest. It was observed that the changes in exercise tolerance are significant in both comparisons, but most significant when sub-grouped by PVR at rest. Results showed that patients over 2 years old with high PVR are above or close to the upper tolerable limit of OER (0.32) at baseline. Patients with high PVR at rest had very poor exercise tolerance while patients with low PVR at rest could tolerate low exercise conditions. In general, ventricular function of SV patients is too poor to increase CI and fulfill exercise requirements. The presented mathematical model provides a framework to estimate the hemodynamic performance of BDG patients at different exercise levels according to patient specific data. Published by Elsevier Ltd.

Expression of the angiogenic mediator, angiopoietin-like 4, in the eyes of patients with proliferative sickle retinopathy.

Directory of Open Access Journals (Sweden)

Kathleen Jee

Full Text Available The recent success of therapies directly targeting the angiogenic mediator, vascular endothelial growth factor (VEGF, for the treatment of proliferative diabetic retinopathy has encouraged clinicians to extend the use of anti-VEGF therapies for the treatment of another ischemic retinal vascular disease, proliferative sickle cell retinopathy (PSR, the most common cause of irreversible blindness in patients with sickle cell disease. However, results from case reports evaluating anti-VEGF therapies for PSR have been mixed. This highlights the need to identify alternative therapeutic targets for the treatment of retinal neovascularization in sickle cell patients. In this regard, angiopoietin-like 4 (ANGPTL4 is a novel angiogenic factor regulated by the transcription factor, hypoxia-inducible factor 1, the master regulator of angiogenic mediators (including VEGF in ischemic retinal disease. In an effort to identify alternative targets for the treatment of sickle cell retinopathy, we have explored the expression of ANGPTL4 in the eyes of patients with PSR. To this end, we examined expression and localization of ANGPTL4 by immunohistochemistry in autopsy eyes from patients with known PSR (n = 5 patients. Complementary studies were performed using enzyme-linked immunosorbent assays in aqueous (n = 8; 7 patients, 2 samples from one eye of same patient and vitreous (n = 3 patients samples from a second group of patients with active PSR. We detected expression of ANGPTL4 in neovascular tissue and in the ischemic inner retina in PSR, but not control, eyes. We further observed elevated expression of ANGPTL4 in the aqueous and vitreous of PSR patients compared to controls. These results suggest that ANGPTL4 could contribute to the development of retinal neovascularization in sickle cell patients and could therefore be a therapeutic target for the treatment of PSR.

The prognostic value of oncogenic antigen 519 (OA-519) expression and proliferative activity detected by antibody MIB-1 in node-negative breast cancer

DEFF Research Database (Denmark)

Jensen, V; Ladekarl, M; Holm-Nielsen, P

1995-01-01

The prognostic value of oncogenic antigen 519 (OA-519) expression and tumour proliferative activity was evaluated in a retrospective series of 118 patients with low-risk breast cancer. Low risk was defined as negative axillary nodes, tumour diameter histological evidence...... analysis, both the MIB-1 index and OA-519 expression were of independent prognostic value (2p breast cancer who might benefit from adjuvant therapy....

Roles of tissue plasminogen activator and its inhibitor in proliferative diabetic retinopathy

Institute of Scientific and Technical Information of China (English)

Shu-Ling; Wu; Dong-Mei; Zhan; Shu-Hong; Xi; Xiang-Lian; He

2014-01-01

AIM:To investigate the role of tissue plasminogen activator(t-PA) and plasminogen activator inhibitor(PAI)in proliferative diabetic retinopathy(PDR) and to discuss the correlations among t-PA, PAI and vascular endothelial growth factor(VEGF) expressions.METHODS:A total of 36 vitreous samples were collected from 36 patients with PDR(PDR group), and 17 vitreous samples from 17 patients with idiopathic macular hole were used as control. The concentrations of t-PA, PAI and VEGF in samples were determined by ELISA method. The correlations among t-PA, PAI and VEGF expressions were discussed.RESULTS:The concentrations of t-PA, PAI and VEGF in the PDR group were significantly higher than those in the control group(P <0.001). The t-PA and PAI expressions were highly correlated with the VEGF expression(P <0.001).CONCLUSION:In addition to VEGF, a variety of bioactive substances, such as t-PA and PAI, are involved in the pathogenesis involved in the angiogenesis of PDR.VEGF can activate t-PA expression, resulting in collagen tissue degradation and angiogenesis. VEGF may also activate the mechanism for endogenous anti-neovascularization.

A comparative study of proliferative activity and tumor stage of pregnancy-associated melanoma (PAM) and non-PAM in gestational age women.

Science.gov (United States)

Merkel, Emily A; Martini, Mary C; Amin, Sapna M; Yélamos, Oriol; Lee, Christina Y; Sholl, Lauren M; Rademaker, Alfred W; Guitart, Joan; Gerami, Pedram

2016-01-01

The influence of pregnancy on the development, progression, and prognosis of melanoma is controversial. We sought to compare clinical characteristics, histologic features, and proliferative activity in pregnancy-associated melanoma (PAM) and melanoma in nonpregnant women of reproductive age (non-PAM). In this retrospective cohort study, we reviewed medical records and pathology reports from women given a diagnosis of melanoma between 2006 and 2015. We also examined tumor proliferation rates using mitotic count and 2 immunohistochemical markers of proliferation, phosphohistone H3 and Ki-67. In 50 PAM and 122 non-PAM cases, a diagnosis of melanoma in situ was associated with PAM. Among invasive melanomas, there was no difference in proliferative activity between groups. Pregnancy status was also not associated with age at diagnosis, tumor site, Breslow depth, Clark level, ulceration, or overall stage. This was a retrospective study with a small sample size of mostly patients with early-stage melanoma. In our study of primarily early-stage melanoma, pregnancy did not have a significant impact on tumor proliferation. Particularly for patients given a diagnosis of stage I melanoma who are undergoing close surveillance, a history of PAM should not outweigh traditional factors, such as advanced maternal age, in planning future pregnancies. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Prevalence status and association with human papilloma virus of anal squamous proliferative lesions in a patient sample in Taiwan.

Science.gov (United States)

Tsai, Tsen-Fang; Kuo, Guan-Tin; Kuo, Lu-Ting; Hsiao, Cheng-Hsiang

2008-08-01

Anal squamous proliferative lesions, including condyloma, anal high-grade squamous intraepithelial lesion (AHSIL) and squamous cell carcinoma (SCC), are associated with human papilloma virus (HPV) infection. The objectives of the study were to investigate the HPV prevalence of anal squamous proliferative lesion in Taiwan. From 1991 to 2005, 41 cases with condyloma, 12 cases with AHSIL, and 13 cases with SCC were collected. DNA was extracted from the tissue sections of these patients, and the HPV genotype was identified using polymerase chain reaction and gene chip. The integration status of HPV16 DNA was also evaluated by quantitative real-time polymerase chain reaction. Anal condyloma mainly occurred in young males, but AHSIL and anal SCC developed in older patients. In the patients with human immunodeficiency virus (HIV) infection, AHSIL developed much earlier than patients without HIV infection (36 vs. 61 years). HPV DNA was detected in all 56 patients whose specimens contained adequate DNA. High-risk HPVs (type 16, 58, etc.) were mainly detected in the AHSIL and SCC. Multiple HPV infection was found in AHSIL (4 of 12) and condyloma (11 of 34) but was rare in invasive cancer (1 of 12). Seven of 8 patients with HPV16 infection had coexistent episomal and integrated forms. HPV58 is a unique high-risk HPV prevalent in Taiwan. The integration status of HPV seems not correlated with the severity of the dysplasia. In our study, emerging HIV-positive AHSIL in recent years indicates that we should devote more efforts to promote sexual safety among the people who engaged in anal intercourse.

Perfluoroctano líquido como tamponante vitreorretiniano de curta duração no pós-operatório de portadores de descolamento de retina por ruptura gigante Perfluoroctane liquid as a short-term vitreous-retinal tamponade in the postoperative period in patients with retinal detachment due to giant tears

Directory of Open Access Journals (Sweden)

Marcelo Carvalho Ventura

2007-06-01

Full Text Available OBJETIVOS: Relatar os resultados de vitrectomia via pars plana com utilização de perfluocarbono líquido (Perfluoroctano-Ophtalmos®, como tamponante vítreo-retiniano de curta duração, no pós-operatório de portadores de descolamento de retina, por ruptura gigante. MÉTODOS: Estudaram-se dez desses pacientes. Todos os casos eram complicados por vitreorretinopatia proliferativa grau B ou pior com rupturas que variavam em extensão de 90º a 210º. O perfluorocarbono líquido foi introduzido, por via pars plana, com o volume necessário para ultrapassar o limite posterior da ruptura, permanecendo no pós-operatório por cinco dias, estando os pacientes em decúbito dorsal. Após esse período submetiam-se a segunda intervenção para troca do perfluorocarbono líquido para gás ou óleo de silicone. RESULTADOS: Após período de acompanhamento médio de 16,2 ± 12,4 meses (2 a 43 meses, 80% das retinas estavam aplicadas, sendo necessária a repetição desta técnica em 1 caso (10% caso e em 2 casos (20% não houve reaplicação da retina por vitreorretinopatia avançada. Houve melhora da acuidade visual em 5 casos (50%. CONCLUSÃO: Observaram-se bons resultados quanto à aplicação da retina (80% e melhora da acuidade visual (50% quando do uso do perfluorocarbono líquido como tamponante vitreorretiniano de curta duração no pós-operatório de cirurgias de descolamento de retina por rupturas gigantes.PURPOSE: To report pars plana vitrectomy results of intravitreous use of liquid perfluorocarbon as a short-term postoperative tamponade in retinal detachment due to giant tears in a series of patients. METHODS: Ten of those patients, all of them complicated by proliferative vitreoretinopathy grade B or worse, with tear extension varying from 90º to 210º were studied. Perfluorocarbon liquid was injected via pars plana until the posterior tear limit, remaining in the postoperative period during five days, with the patients in supine position

The G protein-coupled receptor GPR30 mediates the proliferative and invasive effects induced by hydroxytamoxifen in endometrial cancer cells

Energy Technology Data Exchange (ETDEWEB)

Du, Gui-Qiang; Zhou, Long; Chen, Xiao-Yue [Department of Obstetrics and Gynecology, The International Peace Maternity and Child Health Hospital of the China Welfare Institute Affiliated to Shanghai Jiao Tong University, 910, Hengshan Road, Shanghai (China); Wan, Xiao-Ping, E-mail: wanxiaoping61@126.com [Department of Obstetrics and Gynecology, The International Peace Maternity and Child Health Hospital of the China Welfare Institute Affiliated to Shanghai Jiao Tong University, 910, Hengshan Road, Shanghai (China); He, Yin-Yan [Department of Obstetrics and Gynecology, Shanghai First People' s Hospital, Shanghai Jiao Tong University, Shanghai (China)

2012-04-06

Highlights: Black-Right-Pointing-Pointer We assessed hydroxytamoxifen (OHT) effects in two endometrial cancer cell lines. Black-Right-Pointing-Pointer GPR30 mediates the proliferative effects induced by OHT. Black-Right-Pointing-Pointer GPR30 mediates the invasive effects induced by OHT. Black-Right-Pointing-Pointer GPR30 expression was up-regulated by OHT in endometrial cancer cell line. -- Abstract: The selective ER modulator tamoxifen (TAM) is the most widely used ER antagonist for treatment of women with hormone-dependent breast tumor. However, long-term treatment is associated with an increased risk of endometrial cancer. The aim of the present study was to demonstrate new insight into the role of G-protein coupled receptor 30 (GPR30) in the activity of TAM, which promoted endometrial cancer. In endometrial cancer cell lines ISHIKAWA and KLE, the potential of 4-hydroxytamoxifen (OHT), the active metabolite of TAM, 17{beta}-estradiol (E2) and G1, a non-steroidal GPR30-specific agonist to promote cell proliferation and invasion was evaluated. All agents above induced high proliferative and invasive effects, while the down-regulation of GPR30 or the interruption of MAPK signal pathway partly or completely prevented the action of the regent. Moreover, the RNA and protein expression of GPR30 was up-regulated by G1, E2 or OHT in both cell lines. The present study provided a new insight into the mechanism involved in the agonistic activity exerted by TAM in the uterus.

The G protein-coupled receptor GPR30 mediates the proliferative and invasive effects induced by hydroxytamoxifen in endometrial cancer cells

International Nuclear Information System (INIS)

Du, Gui-Qiang; Zhou, Long; Chen, Xiao-Yue; Wan, Xiao-Ping; He, Yin-Yan

2012-01-01

Highlights: ► We assessed hydroxytamoxifen (OHT) effects in two endometrial cancer cell lines. ► GPR30 mediates the proliferative effects induced by OHT. ► GPR30 mediates the invasive effects induced by OHT. ► GPR30 expression was up-regulated by OHT in endometrial cancer cell line. -- Abstract: The selective ER modulator tamoxifen (TAM) is the most widely used ER antagonist for treatment of women with hormone-dependent breast tumor. However, long-term treatment is associated with an increased risk of endometrial cancer. The aim of the present study was to demonstrate new insight into the role of G-protein coupled receptor 30 (GPR30) in the activity of TAM, which promoted endometrial cancer. In endometrial cancer cell lines ISHIKAWA and KLE, the potential of 4-hydroxytamoxifen (OHT), the active metabolite of TAM, 17β-estradiol (E2) and G1, a non-steroidal GPR30-specific agonist to promote cell proliferation and invasion was evaluated. All agents above induced high proliferative and invasive effects, while the down-regulation of GPR30 or the interruption of MAPK signal pathway partly or completely prevented the action of the regent. Moreover, the RNA and protein expression of GPR30 was up-regulated by G1, E2 or OHT in both cell lines. The present study provided a new insight into the mechanism involved in the agonistic activity exerted by TAM in the uterus.

The presence of proliferative breast disease with atypia does not influence outcome in invasive breast cancer treated with conservative surgery and radiation

International Nuclear Information System (INIS)

Fowble, B.; Hanlon, A.L.; Patchefsky, A.; Hoffman, J.P.; Sigurdson, E.R.; Goldstein, L.J.

1997-01-01

Purpose: Atypical hyperplasia (AH) (ductal or lobular) represents a marker for an increased risk for subsequent breast cancer in either breast, especially in premenopausal women and those with a positive family history. However, the impact of the presence of AH in association with an invasive breast cancer on ipsilateral breast recurrence rates or contralateral breast cancer in women treated with conservative surgery and radiation is unknown. For a number of clinicians the presence of marked proliferative changes with atypia at the time of diagnosis of an invasive cancer is an indication for mastectomy. In an attempt to address this issue, we compared the outcome of patients (pts) with proliferative disease with atypia to those in whom this pathologic feature was absent. Materials and Methods: From 1982-1994, 1537 women with stage I-II breast cancer underwent excisional biopsy, axillary dissection and radiation. 459 of these women had pathologic evaluation of the background adjacent benign breast tissue and represent the study population. The median followup was 6.3 yrs (range .1-14.5). The median age was 55 yrs (range 24 to 88). 23% had positive axillary nodes. 25% received adjuvant chemotherapy (CMF or CAF) with (9%) or without (16%) tamoxifen. 24% received tamoxifen alone. The study population was divided into 2 groups: 131 pts with atypical hyperplasia (ductal 99 pts, lobular 20 pts, and type not specified 12 pts) and 328 pts with no proliferative changes or proliferative changes without atypia. The comparability of the 2 groups was assessed for the following factors: clinical (race, age, menopausal status, method of detection of primary, primary tumor size, and family history), pathologic (histology, final resection margin, pathologic nodal status, presence or absence of LCIS, histologic subtype DCIS when present and estrogen and progesterone receptor status) and treatment related (re-excision and adjuvant chemotherapy and/or tamoxifen). Outcome was evaluated

Proliferative kidney disease (PKD) agent Tetracapsuloides bryosalmonae in brown trout populations in Estonia.

Science.gov (United States)

Dash, Megha; Vasemägi, Anti

2014-05-13

Proliferative kidney disease (PKD) caused by the myxozoan parasite Tetracapsuloides bryosalmonae is a serious parasitic disease threatening both farmed and wild salmonid populations, but very little is currently known about the distribution of the parasite in the Baltic Sea region. In this study we (1) report the development of a novel multiplex PCR method for fast and reliable screening of T. bryosalmonae; (2) use this multiplex PCR method to show that the PKD agent T. bryosalmonae is widespread in natural brown trout Salmo trutta L. populations in Estonia; (3) evaluate monthly and yearly variation of T. bryosalmonae prevalence in juvenile trout; (4) assess T. bryosalmonae prevalence in different age-classes of fish (0+ vs. 1+ and older) and report the presence of the PKD agent in the kidneys of returning sea trout spawners; and (5) suggest the freshwater bryozoan Plumatella fungosa as a putative invertebrate host of T. bryosalmonae in Estonia. Our results demonstrate a highly heterogeneous distribution of T. bryosalmonae at the micro-geographic scale, indicating that PKD could have an important negative effect on recruitment in Estonian brown trout populations.

Maintenance of donor phenotype after full-thickness skin transplantation from mice with chronic proliferative dermatitis (cpdm/cpdm) to C57BL/Ka and nude mice and vice versa

NARCIS (Netherlands)

Gijbels, M. J.; HogenEsch, H.; Bruijnzeel, P. L.; Elliott, G. R.; Zurcher, C.

1995-01-01

Chronic proliferative dermatitis is a spontaneous mutation in C57BL/Ka mice (cpdm/cpdm) and is characterized by epithelial hyperproliferation, infiltration by eosinophils and macrophages, and vascular dilatation. To elucidate whether these pathologic features are the result of a local (skin) process

Characterisation of cell cycle arrest and terminal differentiation in a maximally proliferative human epithelial tissue: Lessons from the human hair follicle matrix.

Science.gov (United States)

Purba, Talveen S; Brunken, Lars; Peake, Michael; Shahmalak, Asim; Chaves, Asuncion; Poblet, Enrique; Ceballos, Laura; Gandarillas, Alberto; Paus, Ralf

2017-09-01

Human hair follicle (HF) growth and hair shaft formation require terminal differentiation-associated cell cycle arrest of highly proliferative matrix keratinocytes. However, the regulation of this complex event remains unknown. CIP/KIP family member proteins (p21 CIP1 , p27 KIP1 and p57 KIP2 ) regulate cell cycle progression/arrest, endoreplication, differentiation and apoptosis. Since they have not yet been adequately characterized in the human HF, we asked whether and where CIP/KIP proteins localise in the human hair matrix and pre-cortex in relation to cell cycle activity and HF-specific epithelial cell differentiation that is marked by keratin 85 (K85) protein expression. K85 expression coincided with loss or reduction in cell cycle activity markers, including in situ DNA synthesis (EdU incorporation), Ki-67, phospho-histone H3 and cyclins A and B1, affirming a post-mitotic state of pre-cortical HF keratinocytes. Expression of CIP/KIP proteins was found abundantly within the proliferative hair matrix, concomitant with a role in cell cycle checkpoint control. p21 CIP1 , p27 KIP1 and cyclin E persisted within post-mitotic keratinocytes of the pre-cortex, whereas p57 KIP2 protein decreased but became nuclear. These data imply a supportive role for CIP/KIP proteins in maintaining proliferative arrest, differentiation and anti-apoptotic pathways, promoting continuous hair bulb growth and hair shaft formation in anagen VI. Moreover, post-mitotic hair matrix regions contained cells with enlarged nuclei, and DNA in situ hybridisation showed cells that were >2N in the pre-cortex. This suggests that CIP/KIP proteins might counterbalance cyclin E to control further rounds of DNA replication in a cell population that has a propensity to become tetraploid. These data shed new light on the in situ-biography of human hair matrix keratinocytes on their path of active cell cycling, arrest and terminal differentiation, and showcase the human HF as an excellent, clinically

Monitoring tumor proliferative response to radiotherapy using 18F-fluorothymidine in human head and neck cancer xenograft in comparison with Ki-67

International Nuclear Information System (INIS)

Fatema, Chowdhury Nusrat; Yu, Wenwen; Kitagawa, Yoshimasa; Zhao, Songji; Zhao, Yan; Murakami, Masahiro; Nishijima, Ken-ichi; Tamaki, Nagara; Kuge, Yuji

2013-01-01

Although radiotherapy is an important treatment strategy for head and neck cancers, it induces tumor repopulation which adversely affects therapeutic outcome. In this regard, fractionated radiotherapy is widely applied to prevent tumor repopulation. Evaluation of tumor proliferative activity using 18 F-fluorothymidine (FLT), a noninvasive marker of tumor proliferation, may be useful for determining the optimal timing of and dose in the repetitive irradiation. Thus, to assess the potentials of FLT, we evaluated the sequential changes in intratumoral proliferative activity in head and neck cancer xenografts (FaDu) using FLT. FaDu tumor xenografts were established in nude mice and assigned to control and two radiation-treated groups (10 and 20 Gy). Tumor volume was measured daily. 3 H-FLT was injected intravenously 2 h before killing. Mice were killed 6, 24, 48 h, and 7 days after the radiation treatment. Intratumoral 3 H-FLT level was visually and quantitatively assessed by autoradiography. Ki-67 immunohistochemistry (IHC) was performed. In radiation-treated mice, the tumor growth was significantly suppressed compared with the control group, but the tumor volume in these mice gradually increased with time. In the visual assessment, intratumoral 3 H-FLT level diffusely decreased 6 h after the radiation treatment and then gradually increased with time, whereas no apparent changes were observed in Ki-67 IHC. Six hours after the radiation treatment at 10 and 20 Gy, the intratumoral 3 H-FLT level markedly decreased to 45 and 40% of the control, respectively (P 3 H-FLT levels at 48 h and on day 7 were significantly higher than that at 6 h. The intratumoral 3 H-FLT levels in both treated groups were 68 and 60% at 24 h (P<0.001), 71 and 77% at 48 h (P<0.001), and 83 and 81% on day 7 (P=NS) compared with the control group. Intratumoral FLT uptake level markedly decreased at 6 h and then gradually increased with time. Sequential evaluation of intratumoral proliferative

Quantified degree of eccentricity of aortic valve calcification predicts risk of paravalvular regurgitation and response to balloon post-dilation after self-expandable transcatheter aortic valve replacement.

Science.gov (United States)

Park, Jun-Bean; Hwang, In-Chang; Lee, Whal; Han, Jung-Kyu; Kim, Chi-Hoon; Lee, Seung-Pyo; Yang, Han-Mo; Park, Eun-Ah; Kim, Hyung-Kwan; Chiam, Paul T L; Kim, Yong-Jin; Koo, Bon-Kwon; Sohn, Dae-Won; Ahn, Hyuk; Kang, Joon-Won; Park, Seung-Jung; Kim, Hyo-Soo

2018-05-15

Limited data exist regarding the impact of aortic valve calcification (AVC) eccentricity on the risk of paravalvular regurgitation (PVR) and response to balloon post-dilation (BPD) after transcatheter aortic valve replacement (TAVR). We investigated the prognostic value of AVC eccentricity in predicting the risk of PVR and response to BPD in patients undergoing TAVR. We analyzed 85 patients with severe aortic stenosis who underwent self-expandable TAVR (43 women; 77.2±7.1years). AVC was quantified as the total amount of calcification (total AVC load) and as the eccentricity of calcium (EoC) using calcium volume scoring with contrast computed tomography angiography (CTA). The EoC was defined as the maximum absolute difference in calcium volume scores between 2 adjacent sectors (bi-partition method) or between sectors based on leaflets (leaflet-based method). Total AVC load and bi-partition EoC, but not leaflet-based EoC, were significant predictors for the occurrence of ≥moderate PVR, and bi-partition EoC had a better predictive value than total AVC load (area under the curve [AUC]=0.863 versus 0.760, p for difference=0.006). In multivariate analysis, bi-partition EoC was an independent predictor for the risk of ≥moderate PVR regardless of perimeter oversizing index. The greater bi-partition EoC was the only significant parameter to predict poor response to BPD (AUC=0.775, p=0.004). Pre-procedural assessment of AVC eccentricity using CTA as "bi-partition EoC" provides useful predictive information on the risk of significant PVR and response to BPD in patients undergoing TAVR with self-expandable valves. Copyright © 2017 Elsevier B.V. All rights reserved.

Transcatheter Pulmonary Valve Replacement: Current State of Art.

Science.gov (United States)

Alkashkari, Wail; Alsubei, Amani; Hijazi, Ziyad M

2018-03-15

The past couple of decades have brought tremendous advances to the field of pediatric and adult congenital heart disease (CHD). Percutaneous valve interventions are now a cornerstone of not just the congenital cardiologist treating patients with congenital heart disease, but also-and numerically more importantly-for adult interventional cardiologists treating patients with acquired heart valve disease. Transcatheter pulmonary valve replacement (tPVR) is one of the most exciting recent developments in the treatment of CHD and has evolved to become an attractive alternative to surgery in patients with right ventricular outflow tract (RVOT) dysfunction. This review aims to summarize (1) the current state of the art for tPVR, (2) the expanding indications, and (3) the technological obstacles to optimizing tPVR. Since its introduction in 2000, more than ten thousands tPVR procedures have been performed worldwide. Although the indications for tPVR have been adapted earlier from those accepted for surgical intervention, they remain incompletely defined. The new imaging modalities give better assessment of cardiac anatomy and function and determine candidacy for the procedure. The procedure has been shown to be feasible and safe when performed in patients who received pulmonary conduit and or bioprosthetic valves between the right ventricle and the pulmonary artery. Fewer selected patients post trans-annular patch repair for tetralogy of Fallot may also be candidates for this technology. Size restrictions of the currently available valves limit deployment in the majority of patients post trans-annular patch repair. Newer valves and techniques are being developed that may help such patients. Refinements and further developments of this procedure hold promise for the extension of this technology to other patient populations.

Arterial morphology responds differently to Captopril then N-acetylcysteine in a monocrotaline rat model of pulmonary hypertension

Science.gov (United States)

Molthen, Robert; Wu, Qingping; Baumgardt, Shelley; Kohlhepp, Laura; Shingrani, Rahul; Krenz, Gary

2010-03-01

Pulmonary hypertension (PH) is an incurable condition inevitably resulting in death because of increased right heart workload and eventual failure. PH causes pulmonary vascular remodeling, including muscularization of the arteries, and a reduction in the typically large vascular compliance of the pulmonary circulation. We used a rat model of monocrotaline (MCT) induced PH to evaluated and compared Captopril (an angiotensin converting enzyme inhibitor with antioxidant capacity) and N-acetylcysteine (NAC, a mucolytic with a large antioxidant capacity) as possible treatments. Twenty-eight days after MCT injection, the rats were sacrificed and heart, blood, and lungs were studied to measure indices such as right ventricular hypertrophy (RVH), hematocrit, pulmonary vascular resistance (PVR), vessel morphology and biomechanics. We implemented microfocal X-ray computed tomography to image the pulmonary arterial tree at intravascular pressures of 30, 21, 12, and 6 mmHg and then used automated vessel detection and measurement algorithms to perform morphological analysis and estimate the distensibility of the arterial tree. The vessel detection and measurement algorithms quickly and effectively mapped and measured the vascular trees at each intravascular pressure. Monocrotaline treatment, and the ensuing PH, resulted in a significantly decreased arterial distensibility, increased PVR, and tended to decrease the length of the main pulmonary trunk. In rats with PH induced by monocrotaline, Captopril treatment significantly increased arterial distensibility and decrease PVR. NAC treatment did not result in an improvement, it did not significantly increase distensibility and resulted in further increase in PVR. Interestingly, NAC tended to increase peripheral vascular density. The results suggest that arterial distensibility may be more important than distal collateral pathways in maintaining PVR at normally low values.

A spreadsheet to determine the volume ratio for target and breast in partial breast irradiation

International Nuclear Information System (INIS)

Kron, T.; Willis, D.; Miller, J.; Hubbard, P.; Oliver, M.; Chua, B.

2009-01-01

Full text: The technical feasibility of Partial Breast Irradiation (PBI) using external beam radiotherapy depends on the ratio between the evaluation planning target volume (PTV e val) and the whole breast volume (PBI volume ratio = PVR). We aimed to develop a simple method to determine PVR using measurements performed at the time of the planning CT scan. A PVR calculation tool was developed using a Microsoft Excel spreadsheet to determine the PTV from three orthogonal dimensions of the seroma cavity and a given margin on the CT scans. The breast volume is estimated from the separation and breast height in five equally spaced CT slices. The PTV e val and whole breast volume were determined for 29 patients from two centres using the spreadsheet calculation tool and compared to volumes delineated on computerised treatment planning systems. Both the PTV e val and whole breast volumes were underestimated by approximately 25% using the spreadsheet. The resulting PVRs were 1.05 +/- 0.35 (mean +/- 1 S D) times larger than the ones determined from planning. Estimations of the PVR using the calculation tool were achievable in around 5 minutes at the time of CT scanning and allow a prompt decision on the suitability of the patients for PBI.

Clinical and experimental study on angiopoietin-like protein 8 associated with proliferative diabetic retinopathy

Directory of Open Access Journals (Sweden)

Chang-Xia Dong

2017-12-01

Full Text Available AIM: To confirm the role of angiopoietin-like protein 8 (Angptl 8 in proliferative diabetic retinopathy (PDR. METHODS: The sera and aqueous humor of 10 PDR patients and 10 non-diabetic retinopathy (NDR patients (idiopathic macular hole patients were collected and the expression of Angptl 8 was detected by enzyme linked immune-sorbent assay (ELISA. Experimental diabetes mice model was induced with streptozotocin. The expression of glycosylated hemoglobin and Angptl 8 in sera was detected. Recombinant Angptl 8 was re-infused into wild type (WT diabetic mice and spatial frequency threshold and contrast sensitivity were measured. In vitro retinal pigment epithelium (RPE were stimulated by recombinant Angptl 8 for 24h. MMT assay were used to detect cell proliferation. At the same time, qRT-PCR and Western blot was used to measure the expression of proliferation-related factors in PRE cells. RESULTS: The expression of Angptl 8 was markedly increased in the sera and aqueous humor of PDR patients (F=99.02, P<0.0001 in sera; t=10.42, P<0.0001 in aqueous. After successfully establishing the diabetic mice model, we found that glycosylated hemoglobin and Angptl 8 expression levels were increased. Re-infusion of recombinant Angptl 8 into WT diabetic mice could further decrease spatial frequency threshold and contrast sensitivity (P<0.01. In vitro, RPE cells stimulated by recombinant Angptl 8 could increase the relative absorbance of MMT assay (1.486±0.042 vs 1.000±0.104, P<0.05 and proliferating cell nuclear antigen (PCNA expression (0.55±0.01 vs 0.29±0.03, P<0.05. The proliferative effect of Angptl 8 is mainly mediated by increasing the expression of proliferation-activating factors cyclin A1 (4.973±0.205 vs 2.720±0.197, P<0.05, cyclin F (5.690±0.219 vs 4.297±0.292, P<0.05 and E2F2 (2.297±0.102 vs 1.750±0.146, P<0.05, and reducing the expression of proliferation-inhibiting factors cdkn1 (2.370±0.074 vs 3.317±0.135, P<0.05 and cdkn2 (4.793±0

Nuclear Morphometry in Ductal Breast Carcinoma with Correlation to Cell Proliferative Activity and Prognosis

International Nuclear Information System (INIS)

Radwan, M.M.; Amer, K.A.; Mokhtar, N.M.

2003-01-01

Morphometry is the quantitative description of biologic structures. This study was designed to evaluate the efficiency of morphometric measurements in diagnosis and prognosis of patients with breast carcinoma. Methods: Histological samples from 61 patients of invasive duct carcinoma (IDC) of no special type (NST), 12 cases of ductal carcinoma in situ (DCIS) and 14 control breast samples taken from fibrocystic change disease were retrospectively analyzed by computerized nuclear morphometry. All IDC patients underwent modified radical mastectomy without preoperative chemotherapy. The mean follow up was 28±19 months (range] -71). In each case, 25-50 nuclei were measured and the mean nuclear area (MNA), mean nuclear perimeter (MNP), mean maximum nuclear diameter (MMNO) and mean minimal nuclear diameter (Mmnd) were measured. The mean axis ratio (MAR), mean nuclear compactness (MNC), mean nuclear size (MNS) and mean shape factor (MSHF), were calculated mathematically. To measure the nuclear diameters, a new method was employed using the AutoCAD program. Morphometric parameters were compared with different clinico pathologic features, patient's survival and cell proliferative activity as determined by Ki-67 immunostaining which was evaluated quantitatively. Most of the morphometric parameters were significantly higher in DCIS and IDC groups than benign one. In IDC group morphometric features related to nuclear size (MNA, MNP, MMNO, Mmnd and MNS) were significantly correlated to most clinico pathologic features and cell proliferative activity assessed by Ki-67 immunostaining. However, the shape factor failed to achieve this correlation. The univariate analysis using Kaplan Meier curves indicated that short survival time was correlated with high nuclear morphometric values (MNA. MNP, MMND, Mmnd, MNS and MSHF). Moreover, the Spear man correlation analysis showed that Mmnd has the highest converse correlation with survival (r= -0.75, (ρ < 0.0001). In multivariate analysis

Temporal changes in retinal vascular parameters associated with successful panretinal photocoagulation in proliferative diabetic retinopathy

DEFF Research Database (Denmark)

Torp, Thomas Lee; Kawasaki, Ryo; Wong, Tien Yin

2018-01-01

PURPOSE: We aimed to investigate changes in retinal vascular geometry over time after panretinal photocoagulation (PRP) in patients with proliferative diabetic retinopathy (PDR). METHODS: Thirty-seven eyes with PDR were included. Wide-field fluorescein angiography (Optomap, Optos PLC., Dunfermline......, Scotland, UK) was used to diagnose PDR at baseline and to assess activity at follow-up month three and six. At each time-point, a trained grader measured retinal vessel geometry on optic disc (OD) centred images using semiautomated software (SIVA, Singapore I Vessel Assessment, National University...... of Singapore, Singapore) according to a standardized protocol. RESULTS: At baseline, the mean age and duration of diabetes were 52.8 and 22.3 years, and 65% were male. Mean HbA1c was 69.9 mmol/mol, and blood pressure was 155/84 mmHg. Of the 37 eyes with PDR, eight (22%) eyes had progression at month three...

Two novel prenylated kaempferol derivatives from fresh bud's fur of Platanus acerifolia and their anti-proliferative activities.

Science.gov (United States)

Zuo, Bo; Liao, Zhi-Xin; Xu, Chen; Liu, Chao

2016-01-06

Two novel prenylated kaempferol derivatives (1, 2), together with seven known metabolites were isolated from ethanol extract of fresh Platanus acerifolia bud's fur by multistep chromatographic processing. Structure of compounds 1 and 2 was confirmed by 1D, 2D NMR spectra and HR-ESI-MS. In addition, compound 1 was further analysed by X-ray crystallography. Anti-proliferative activities in vitro against human breast carcinoma (MCF-7) and human hepatocellular carcinoma (Hep-G2) cell lines for compound 1, 2 and 8 were evaluated. Compound 1 exhibited cytotoxic activity towards MCF-7 and Hep-G2 cell lines with the IC 50 values 38.2 and 39.5 μM, respectively. Moreover, compound 2 showed weak cytotoxic activities against the two cell lines.

Associação entre tamanho e potencial proliferativo em neurinomas do acústico Size and proliferative index correlation in acoustic neuromas

Directory of Open Access Journals (Sweden)

Oswaldo Inácio de Tella

2006-03-01

Full Text Available Schwanomas do acústico são os tumores mais freqüentes localizados no ângulo pontocerebelar. Os mecanismos moleculares que levam a sua geração e crescimento ainda não são bem conhecidos. Várias características clínicas, radiológicas e imuno-histoquímicas já foram estudadas e correlacionadas ao crescimento tumoral. Estudamos e correlacionamos aspectos clínicos e imuno-histoquímicos (MIB-1 de 11 schwanomas do acústico operados no Hospital São Paulo/UNIFESP. O tamanho dos tumores correlacionou-se com o índice proliferativo (Ki-67, não havendo correlação com significância estatística entre a idade dos pacientes, duração dos sintomas e índice proliferativo.Acoustic neuromas are the most common tumors in the cerebellopontine angle. The molecular mechanisms involved in generation and growth of these tumors are not completly elucidated. Many radiological, clinic and imunohistochemystry data were correlated to tumor growth. We studied 11 acoustic neuromas surgically treated at Hospital São Paulo/Unifesp and correlated clinical and radiological data with proliferative index (Ki-67. The size of the tumors were positively correlationated with proliferative index. No other correlation had statistic significativity.

Ki67 Proliferative Index in Carcinoid Tumors Involving Ovary.

Science.gov (United States)

Zhang, Xiaotun; Jones, Andrea; Jenkins, Sarah M; Huang, Yajue

2018-03-01

Primary ovarian carcinoid tumors are rare neoplasms that constitute less than 0.1% of all ovarian carcinomas. However, carcinoid tumors metastatic to ovaries are more common. Cell proliferative rate is an important factor in the determination of neuroendocrine tumor prognosis. Limited data are available as regards Ki67 proliferation index in predicting the physiological features of carcinoid tumors involving the ovary. Pathology files of Mayo Clinic Rochester (1995-2014) were searched, and clinical information was collected from medical records. All cases were stained with an antibody against Ki67, and digital analysis was performed with digital imaging analysis. A total of 36 cases (median age 64 years, range 33-83 years), including 9 primary (median age 68 years, range 33-73 years) and 27 metastatic carcinoid cases (median age 64 years, range 36-83 years), were investigated in the current study. Seven out of nine (77.8%) primary ovarian carcinoids are associated with mature teratoma. Twenty two metastatic carcinoids (81.5%) were from the GI tract, four (14.8%) from the pancreas, and one (3.7%) from the posterior thorax location. There was significant difference of Ki67 index between primary (median 2.3%, range, 0.6-8.4%) and metastatic carcinoid tumors (median 9.7%, range, 1.3-46.7%) (p = 0.002). The survival time is much shorter among patients with metastatic carcinoid tumor (median survival 5.8 years) comparing to primary ovarian carcinoid tumor (median 14.2 years) (p = 0.0005). A strong association between Ki67 index and patient survival time was identified (Hazard ratio for 1-percentage point increase 1.11, p = 0.001). Comparing to primary ovarian carcinoid tumor, metastatic carcinoid usually exhibits a higher Ki67 index and a worse outcome.

Identification of Genetic on Blood Serum Protein of Prolific Ewes

Science.gov (United States)

Sutiyono; Ondho, Y. S.; Setiatin, E. T.; Sutopo; Laily, A. N.; Prasetyowati, D. E.; Noviani, F.

2018-02-01

The aim of the research was to identify the genetic specification of blood plasma protein in ewes that are prolific. The material of study of local sheep in Bawen and Jambu Sub-district of Semarang Regency is 132 which is determined by purposive sampling that have been give lambing three times. Ewes were divided into three groups that always has a single child (L1), ever had twins (L2) and twins more than two (LM2). Blood sampling was performed using dispossible syringe in jugular vein as much as 5 ml per ewe. Blood plasma was analyzed by Polyacrylamide Gel Electrophoresis-Thin Layer (PAGETLE) method in Biochemistry Laboratory of Veterinary Faculty of Gadjah Mada University. Data analysis is using descriptive statistics and the laws of equilibrium Hardy-Weberg. The research parameters were comparison type of ewes and frequency genetic of protein of blood serum. The results showed that the parent comparisons of L1, L2 and LM2 were 66 (50.00%), 49 (37.12%) and 17 (12.88%), respectively. The frequency genes haven a high propensity to relationship of prolificacy nature parent are Pal2, AlbB, CPF, TFB, PTFS and AmlB on pointes, 67.65, 55.88, 91.17, 70.59, 79.41 and 91.18%. Conclusion the mostly LM2 ewes have genotypes Pal1Pal2, AlbBAlbC, CpFCpF, TfATfB, PtfSPtfS and AmlBAmlB whit frequency are 52.94%, 52.94%, 88.24, 47.06, 64.71 and 88.24% respectively.

Curative effect of Ranibizumab combined with laser photocoagulation for proliferative diabetic retinopathy

Directory of Open Access Journals (Sweden)

Fan-Yi Meng

2018-04-01

Full Text Available AIM:To investigate the clinical efficacy of Ranibizumab combined with laser photocoagulation in the treatment of proliferative diabetic retinopathy(PDR. METHODS: Totally 80 patients(101 eyeswith PDR admitted to our hospital from October 2014 and October 2016 were selected and divided into the observation group and the control group, with 50 eyes and 51 eyes respectively. The patients in the control group(50 eyeswere treated with panretinal photocoagulation(PRP, and the patients in observation group(51 eyeswere treated with ranibizumab on the basis of PRP treatment. Best corrected visual acuity(BCVAwas compared before and after surgery 1, 3, and 6mo. Optical coherence tomography(OCTwas used to examine the central macular thickness(CMTand the area of neovascularization at each timepoints. Then the laser spot number, laser energy and energy density were compared between the two groups and the adverse reactions were recorded. RESULTS: Postoperative BCVA of the two groups significantly increased, and the BCVA of observation group were significantly higher than that of the control group after surgery 1, 3, 6mo, the difference was statistically significant(PPPCONCLUSION: Ranibizumab combined with laser in the treatment of PDR is an effective and safe way to improve BCVA, reduce CMT, and eliminate new blood vessels with less required laser energy.

Echocardiographic Assessment of Pulmonary Arterial Hypertension for Pediatricians and Neonatologists

Directory of Open Access Journals (Sweden)

Gregory James Skinner

2017-09-01

Full Text Available There is a growing awareness of the role that increased pulmonary vascular resistance (PVR plays in many pathologies; therefore, assessment of pulmonary artery pressure (PAP is an increasingly requested investigation in the critical care environment. This article will go through the basic concepts regarding PAP and PVR, then will go on to outline the various echocardiographic parameters which are used to assess them. Finally, an outline of how to undertake this assessment will be presented.

Retinal phenotype-genotype correlation of pediatric patients expressing mutations in the Norrie disease gene.

Science.gov (United States)

Wu, Wei-Chi; Drenser, Kimberly; Trese, Michael; Capone, Antonio; Dailey, Wendy

2007-02-01

To correlate the ophthalmic findings of patients with pediatric vitreoretinopathies with mutations occurring in the Norrie disease gene (NDP). One hundred nine subjects with diverse pediatric vitreoretinopathies and 54 control subjects were enrolled in the study. Diagnoses were based on retinal findings at each patient's first examination. Samples of DNA from each patient underwent polymerase chain reaction amplification and direct sequencing of the NDP gene. Eleven male patients expressing mutations in the NDP gene were identified in the test group, whereas the controls demonstrated wild-type NDP. All patients diagnosed as having Norrie disease had mutations in the NDP gene. Four of the patients with Norrie disease had mutations involving a cysteine residue in the cysteine-knot motif. Four patients diagnosed as having familial exudative vitreoretinopathy were found to have noncysteine mutations. One patient with retinopathy of prematurity had a 14-base deletion in the 5' untranslated region (exon 1), and 1 patient with bilateral persistent fetal vasculature syndrome expressed a noncysteine mutation in the second exon. Mutations disrupting the cysteine-knot motif corresponded to severe retinal dysgenesis, whereas patients with noncysteine mutations had varying degrees of avascular peripheral retina, extraretinal vasculature, and subretinal exudate. Patients exhibiting severe retinal dysgenesis should be suspected of carrying a mutation that disrupts the cysteine-knot motif in the NDP gene.

Practical determination of aortic valve calcium volume score on contrast-enhanced computed tomography prior to transcatheter aortic valve replacement and impact on paravalvular regurgitation: Elucidating optimal threshold cutoffs.

Science.gov (United States)

Bettinger, Nicolas; Khalique, Omar K; Krepp, Joseph M; Hamid, Nadira B; Bae, David J; Pulerwitz, Todd C; Liao, Ming; Hahn, Rebecca T; Vahl, Torsten P; Nazif, Tamim M; George, Isaac; Leon, Martin B; Einstein, Andrew J; Kodali, Susheel K

The threshold for the optimal computed tomography (CT) number in Hounsfield Units (HU) to quantify aortic valvular calcium on contrast-enhanced scans has not been standardized. Our aim was to find the most accurate threshold to predict paravalvular regurgitation (PVR) after transcatheter aortic valve replacement (TAVR). 104 patients who underwent TAVR with the CoreValve prosthesis were studied retrospectively. Luminal attenuation (LA) in HU was measured at the level of the aortic annulus. Calcium volume score for the aortic valvular complex was measured using 6 threshold cutoffs (650 HU, 850 HU, LA × 1.25, LA × 1.5, LA+50, LA+100). Receiver-operating characteristic (ROC) analysis was performed to assess the predictive value for > mild PVR (n = 16). Multivariable analysis was performed to determine the accuracy to predict > mild PVR after adjustment for depth and perimeter oversizing. ROC analysis showed lower area under the curve (AUC) values for fixed threshold cutoffs (650 or 850 HU) compared to thresholds relative to LA. The LA+100 threshold had the highest AUC (0.81), and AUC was higher than all studied protocols, other than the LA x 1.25 and LA + 50 protocols, where the difference approached statistical significance (p = 0.05, and 0.068, respectively). Multivariable analysis showed calcium volume determined by the LAx1.25, LAx1.5, LA+50, and LA+ 100 HU protocols to independently predict PVR. Calcium volume scoring thresholds which are relative to LA are more predictive of PVR post-TAVR than those which use fixed cutoffs. A threshold of LA+100 HU had the highest predictive value. Copyright © 2017 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

A pleural vacuum relief device for pleural drain unit use in the hyperbaric environment.

Science.gov (United States)

Gelsomino, Marco; Tsouras, Theo; Millar, Ian; Fock, Andrew

2017-09-01

When a standard water-seal pleural drain unit (PDU) is used under hyperbaric conditions there are scenarios where excessive negative intrapleural pressure (IPP) and/or fluid reflux can be induced, risking significant morbidity. We developed and tested a pleural vacuum relief (PVR) device which automatically manages these risks, whilst allowing more rapid hyperbaric pressure change rates. The custom-made PVR device consists of a one-way pressure relief valve connected in line with a sterile micro filter selected for its specific flow capacity. The PVR device is designed for connection to the patient side sampling port of a PDU system, allowing inflow of ambient air whenever negative pressure is present, creating a small, controlled air leak which prevents excessive negative pressure. The hyperbaric performance of a Pleur-Evac A-6000 intercostal drain was assessed with and without this added device by measuring simulated IPP with an electronic pressure monitor connected at the patient end of the PDU. IPP readings were taken at 10, 15, 20 and 30 cmH₂O of suction (set on the drain unit) at compression rates of 10, 30, 60, 80, 90 and 180 kPa·min⁻¹ to a pressure of 280 kPa. At any compression rate of > 10 kPa·min⁻¹, the negative IPP generated by the Pleur-Evac A-6000 alone was excessive and resulted in back flow through the PDU water seal. By adding the PVR device, the generated negative IPP remains within a clinically acceptable range, allowing compression rates of at least 30 kPa·min⁻¹ with suction settings up to -20 cmH₂O during all phases of hyperbaric treatment. The PDU PVR device we have developed works well, minimising attendant workload and automatically avoiding the excessive negative IPPs that can otherwise occur. This device should only be used with suction.

Frequency of recurrent urinary tract infection in patients with pelvic organ prolapse

Directory of Open Access Journals (Sweden)

Töz E

2015-01-01

Full Text Available Emrah Töz,1 Sefa Kurt,2 Çagdas Sahin,1 Mehmet Tunç Canda3 1Department of Obstetrics and Gynecology, Tepecik Training and Research Hospital, Izmir, Turkey; 2Department of Obstetrics and Gynecology, Izmir Dokuz Eylül University, Izmir, Turkey; 3Department of Obstetrics and Gynecology, Kent Hospital, Izmir, Turkey Purpose: The aim of the study was to investigate the existence of a relationship between pelvic organ prolapse (POP and recurrent urinary tract infection (UTI. Materials and methods: The hospital database was searched for women diagnosed with pelvic floor disorders and all medical records were reviewed for recurrent UTI, diagnosed by two or more positive urine cultures taken within 12 months of each other. The control group was created using one-to-one matching for age and menopausal status. The prevalence of recurrent UTI in these patients were compared. Results: The mean age of the 210 participants was 54.64±5.15 years. We found no association between POP and recurrent UTI. In the prolapse group, 22 women (21% had recurrent UTI compared with 19 women (18% in the control group (P=0.316. Post-void residual (PVR volumes >50 mL were associated with increased prevalence of recurrent UTI. Conclusion: POP is not a risk factor for recurrent UTI, but women with POP are more likely to have high PVR volumes. High PVR volumes increase the risk of recurrent UTI. Clinical examination and ultrasound assessment of PVR should be performed in all women presenting with prolapse and UTI. Elevated PVR is the most significant risk factor, linking POP with recurrent UTI. Keywords: recurrent urinary tract infection, pelvic organ prolapse, post-void residual

Mutational analysis of BRAF and KRAS in ovarian serous borderline (atypical proliferative) tumours and associated peritoneal implants

DEFF Research Database (Denmark)

Ardighieri, Laura; Zeppernick, Felix; Hannibal, Charlotte G

2014-01-01

There is debate as to whether peritoneal implants associated with serous borderline tumours/atypical proliferative serous tumours (SBT/APSTs) of the ovary are derived from the primary ovarian tumour or arise independently in the peritoneum. We analysed 57 SBT/APSTs from 45 patients with advanced......), 34 (53.9%) had KRAS mutations and 14 (22%) had BRAF mutations, of which identical KRAS mutations were found in 34 (91%) of 37 SBT/APST-implant pairs and identical BRAF mutations in 14 (100%) of 14 SBT/APST-implant pairs. Wild-type KRAS and BRAF (at the loci investigated) were found in 11 (100%) of 11...... SBT/APST-implant pairs. Overall concordance of KRAS and BRAF mutations was 95% in 59 of 62 SBT/APST-implant (non-invasive and invasive) pairs (p identical KRAS or BRAF...

Extraction, purification and anti-proliferative activities of polysaccharides from Lentinus edodes.

Science.gov (United States)

Zhao, Yong-Ming; Wang, Jin; Wu, Zhi-Gang; Yang, Jian-Ming; Li, Wei; Shen, Li-Xia

2016-12-01

In this study, the enzyme-assisted extraction of polysaccharides from Lentinus edodes (LEPs) was optimized by response surface methodology, and a preliminary characterization of the extracted LEPs and their anti-proliferative activities were investigated. An orthogonal assay was constructed to determine the optimal amounts of cellulase, papain and pectinase, which were 15, 20 and 15g/kg, respectively. Then effects of extraction conditions were evaluated and optimized using a Box-Behnken design. The results showed that the highest polysaccharides yield of 15.65% was achieved with an extraction temperature of 54°C, pH 5.0, enzymatic treatment time of 93min and a liquid/material ratio of 29:1mL/g, which correlated well with the predicted yield of 15.58%. Subsequently, the crude LEPs were further purified by DEAE-cellulose and Sephadex-100 chromatography to obtain two fractions, which were designated as LEP-1 and LEP-2 and their monosaccharide compositions were characterized by GC. Fourier-transform infrared spectra demonstrated that LEP-1 and LEP-2 were distinct from each other regarding their chemical structures. In addition, the LEPs exhibited inhibition of cell proliferation on HCT-116 and HeLa cells in vitro. In summary, this study provides an efficient enzyme-assisted extraction for LEPs, which can be used as natural antitumor agents in the pharmaceutical and functional food industries. Copyright © 2016 Elsevier B.V. All rights reserved.

Endoilluminator-assisted scleral buckling: Our results

Directory of Open Access Journals (Sweden)

Varun Gogia

2014-01-01

Full Text Available Aims: The aim was to evaluate the long-term surgical outcomes of endoillumination assisted scleral buckling (EASB in primary rhegmatogenous retinal detachment (RRD. Methods: Twenty-five eyes of 25 patients with primary RRD and proliferative vitreoretinopathy ≤C2 where any preoperative break could not be localised, were included. All patients underwent 25 gauge endoilluminator assisted rhegma localisation. Successful break determination was followed by cryopexy and standard scleral buckling under surgical microscope. Anatomical and functional outcomes were evaluated at the end of 2 years. Results: At least one intraoperative break could be localized in 23 of 25 (92% eyes. Median age of these patients was 46 years (range: 17-72. Thirteen eyes (56.52% were phakic, 8 (34.78% were pseudophakic and 2 (8.6% were aphakic. Anatomical success (attachment of retina was achieved in 22 (95.63% of 23 eyes with EASB. All eyes remained attached at the end of 2 years. Significant improvement in mean visual acuity (VA was achieved at the end of follow-up (1.09 ± 0.46 log of the minimum angle of resolution [logMAR] compared with preoperative VA (1.77 ± 0.28 logMAR (P < 0.001. Conclusion: EASB can be considered an effective alternative to vitreoretinal surgery in simple retinal detachment cases with the added advantage of enhanced microscopic magnification and wide field illumination.

Scleral depressed vitreous shaving, 360 laser, and perfluoropropane (C 3 F 8 for retinal detachment

Directory of Open Access Journals (Sweden)

Vivek Chaturvedi

2014-01-01

Full Text Available Purpose : To review the characteristics and outcomes of patients who underwent pars plana vitrectomy (PPV with scleral depressed vitreous shaving, 360 degree peripheral endolaser, and 14% C3F8 gas for rhegmatogenous retinal detachment (RRD. Materials and Methods : A retrospective review of a consecutive series of patients who underwent primary repair of RRD by PPV with scleral depressed vitreous shaving, 360 degree peripheral endolaser, and 14% perfluoropropane (C 3 F 8 was conducted. Patients with less than 3 months follow-up, previous retinal surgery, and higher than grade B proliferative vitreoretinopathy were excluded. Results : Ninety-one eyes were included in the study. The mean age was 60.1 years. The mean follow-up was 13.7 months. The macula was detached in 63% (58/91 of the eyes. The reattachment rate after one surgical procedure was 95% (86/91 while overall reattachment rate was 100%. There was no statistically significant difference between reattachment rates of superior, nasal/temporal, or inferior RRDs. The mean final best corrected visual acuity (BCVA was 20/40. Of all the patients, 66% of patients with macula-off RRDs had a final BCVA of 20/40 or better. Conclusions: PPV with scleral depressed vitreous shaving, 360 degree peripheral endolaser, and 14% C 3 F 8 leads to successful anatomical reattachment with visual improvement in patients with primary RRD.

Subretinal Fluid Levels of Signal-Transduction Proteins and Apoptosis Molecules in Macula-Off Retinal Detachment Undergoing Scleral Buckle Surgery.

Science.gov (United States)

Carpineto, Paolo; Aharrh-Gnama, Agbeanda; Ciciarelli, Vincenzo; Borrelli, Enrico; Petti, Francesco; Aloia, Raffaella; Lamolinara, Alessia; Di Nicola, Marta; Mastropasqua, Leonardo

2016-12-01

To evaluate signal transduction and early apoptosis protein levels in subretinal fluid collected during scleral buckling surgery for macula-off rhegmatogenous retinal detachment (RRD). Our aim was to assess both their relation with RRD features and their influence on the posttreatment outcome. Thirty-three eyes of 33 RRD patients scheduled for scleral buckle surgery were enrolled in the study. Undiluted subretinal fluid samples were collected during surgery and analyzed via magnetic bead-based immunoassay. All patients underwent a complete ophthalmologic evaluation at baseline and at each follow-up visit (months 1, 3, and 6). Moreover, both at baseline and at the postsurgery month 6 visit, the patients were tested by means of spectral-domain optical coherence tomography (SD-OCT) in order to evaluate the average ganglion cell-inner plexiform complex thickness, as well as the photoreceptor inner segment/outer segment junction status. Patients' clinical features (retinal detachment size, detachment duration, and occurrence of proliferative vitreoretinopathy) were associated with several early apoptotic factors (caspase-8, caspase-9, and B-cell lymphoma 2 [Bcl-2]-associated death promoter [BAD]). Furthermore, both early apoptosis factors (caspase-8, Bcl-2, and p53) and signal-transduction proteins (ERK 1/2) were found to influence the postsurgery month 3 OCT characteristics. Signal-transduction proteins and early apoptosis proteins are associated with different clinical features and postsurgery outcomes.

Uric acid stimulates proliferative pathways in vascular smooth muscle cells through the activation of p38 MAPK, p44/42 MAPK and PDGFRβ.

Science.gov (United States)

Kırça, M; Oğuz, N; Çetin, A; Uzuner, F; Yeşilkaya, A

2017-04-01

Hyperuricemia and angiotensin II (Ang II) may have a pathogenetic role in the development of hypertension and atherosclerosis as well as cardiovascular disease (CVD) and its prognosis. The purpose of this study was to investigate whether uric acid can induce proliferative pathways of vascular smooth muscle cell (VSMC) that are thought to be responsible for the development of CVD. The phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK), p44/42 mitogen-activated protein kinase (p44/42 MAPK) and platelet-derived growth factor receptor β (PDGFRβ) was measured by Elisa and Western blot techniques to determine the activation of proliferative pathways in primary cultured VSMCs from rat aorta. Results demonstrated that uric acid can stimulate p38 MAPK, p44/42 MAPK and PDGFRβ phosphorylation in a time- and concentration-dependent manner. Furthermore, treatment of VSMCs with the angiotensin II type I receptor (AT1R) inhibitor losartan suppressed p38 MAPK and p44/42 MAPK induction by uric acid. The stimulatory effect of uric acid on p38 MAPK was higher compared to that of Ang II. The results of this study show for the first time that uric acid-induced PDGFRβ phosphorylation plays a crucial role in the development of CVDs and that elevated uric acid levels could be a potential therapeutical target in CVD patients.

Pulmonary hypertension of the newborn.

Science.gov (United States)

Stayer, Stephen A; Liu, Yang

2010-09-01

Pulmonary hypertension presenting in the neonatal period can be due to congenital heart malformations (most commonly associated with obstruction to pulmonary venous drainage), high output cardiac failure from large arteriovenous malformations and persistent pulmonary hypertension of the newborn (PPHN). Of these, the most common cause is PPHN. PPHN develops when pulmonary vascular resistance (PVR) remains elevated after birth, resulting in right-to-left shunting of blood through foetal circulatory pathways. The PVR may remain elevated due to pulmonary hypoplasia, like that seen with congenital diaphragmatic hernia; maldevelopment of the pulmonary arteries, seen in meconium aspiration syndrome; and maladaption of the pulmonary vascular bed as occurs with perinatal asphyxia. These newborn patients typically require mechanical ventilatory support and those with underlying lung disease may benefit from high-frequency oscillatory ventilation or extra-corporeal membrane oxygenation (ECMO). Direct pulmonary vasodilators, such as inhaled nitric oxide, have been shown to improve the outcome and reduce the need for ECMO. However, there is very limited experience with other pulmonary vasodilators. The goals for anaesthetic management are (1) to provide an adequate depth of anaesthesia to ablate the rise in PVR associated with surgical stimuli; (2) to maintain adequate ventilation and oxygenation; and (3) to be prepared to treat a pulmonary hypertensive crisis--an acute rise in PVR with associated cardiovascular collapse.

Pelvic congestion syndrome masquerading as osteoarthritis of the hip

Directory of Open Access Journals (Sweden)

Scott J Dos Santos

2016-12-01

Full Text Available Objectives: Pelvic congestion syndrome (PCS is associated with pelvic vein reflux (PVR, occasionally secondary to venous compression. Its symptoms, usually intra-pelvic, are alleviated following the abolition of this reflux by pelvic vein embolisation (PVE. The objective of this report is to present two cases of left hip pain, erroneously diagnosed as osteoarthritis, which disappeared after successful PVE and abolition of PVR. Methods: Two females presented with lower limb varicose veins, and also had a history of left-sided hip pain. Both had previously been investigated for the hip pain and diagnosed as osteoarthritis despite minimal arthritic changes on pelvic X-rays. During investigation for lower limb varicose veins, both showed a pelvic origin for their leg veins and hence underwent transvaginal duplex ultrasound. This revealed PVR, and PVE was planned in both patients. Results: Both patients underwent PVE and reported ‘miraculous’ resolution of left hip pain and also PCS symptoms including pelvic pain, irritable bowel issues and the disappearance of pelvic dragging, with almost immediate disappearance of vulval and vaginal varicosities. One patient also noted reduced clitoral sensitivity. Conclusion: Manifestations of PCS may vary in terms of intra- or extra-pelvic signs. PCS and PVR should be considered in the differential diagnosis of patients with arthritic symptoms in the hip without evident radiographic evidence.

Effects of various timings and concentrations of inhaled nitric oxide in lung ischemia-reperfusion. The Paris-Sud University Lung Transplantation Group.

Science.gov (United States)

Murakami, S; Bacha, E A; Mazmanian, G M; Détruit, H; Chapelier, A; Dartevelle, P; Hervé, P

1997-08-01

Experimental studies reveal that inhaled nitric oxide (NO) can prevent, worsen, or have no effect on lung injury in the setting of ischemia-reperfusion (I-R). We tested the hypothesis that these disparate effects could be related to differences in the timing of administration and/or concentration of inhaled NO during I-R. Isolated rat lungs were subjected to 1-h periods of ischemia followed by 1-h periods of blood reperfusion. We investigated the effects of NO (30 ppm) given during ischemia, NO (30 or 80 ppm) begun immediately at reperfusion, or NO (30 ppm) given 15 min after the beginning of reperfusion, on total pulmonary vascular resistance (PVR), the coefficient of filtration (Kfc), the lung wet/dry weight ratio (W/D) of lung tissue, and lung myeloperoxidase activity (MPO). A control group did not receive NO. NO given during ischemia had no effect on Kfc or MPO, but decreased PVR. NO (30 ppm) during reperfusion (early or delayed) decreased PVR, W/D, Kfc and MPO. NO at 80 ppm decreased PVR and MPO but not W/D or Kfc. In conclusion, NO at 30 ppm, given immediately or in a delayed fashion during reperfusion, attenuates I-R-induced lung injury. NO at 30 ppm given during ischemia or at 80 ppm during reperfusion is not protective.

Proliferative sickle cell retinopathy associated with sickle cell trait and gestational diabetes: case report Retinopatia falciforme proliferativa associada a traço falciforme e diabetes gestacional: relato de caso

Directory of Open Access Journals (Sweden)

Jefferson Augusto Santana Ribeiro

2009-06-01

Full Text Available Proliferative sickle cell retinopathy is an uncommon complication in individuals with sickle cell trait (AS. However, the risk for proliferative retinopathy development is increased in patients with AS hemoglobinopathy associated with systemic conditions or ocular trauma. A case of a patient with AS hemoglobinopathy who developed proliferative sickle cell retinopathy after the occurrence of gestational diabetes and pregnancy-induced hypertension is reported. Hemoglobin electrophoresis revealed presence of A2 5.0%, S 35.0% and A 53.2%. The present case emphasizes the importance of evaluating systemic comorbidities in patients with sickle cell trait during pregnancy since sickle cell retinopathy can progress rapidly, as well as the importance of regular eye fundus examination in these patients.Retinopatia falciforme proliferativa é uma complicação incomum em indivíduos com traço falciforme, havendo, porém, risco aumentado de desenvolver retinopatia proliferativa em pacientes com hemoglobinopatia AS associada a condições sistêmicas ou trauma ocular. Neste artigo será apresentado um caso de paciente com diabetes gestacional, hipertensão arterial sistêmica associada à gravidez e traço falciforme. Eletroforese de hemoglobinas revelou a presença de A2 5,0%, S 35,0% e A 53,2%. Este caso ressalta a importância da avaliação de comorbidades sistêmicas em pacientes com traço falciforme no período gestacional, uma vez que pode ocorrer rápida progressão da retinopatia falciforme, devendo-se realizar também exames regulares do fundo de olho nestes pacientes.

Proliferative kinetics of the haematopoietic stem cells of the mouse after several weeks of reconvalescence of an irradiation attack

International Nuclear Information System (INIS)

Huebner, G.

1980-01-01

The 125 IDU(iodo-deoxyuridine) tracer-technique was applied for investigating proliferative kinetics. The intention was to reveal a possible persistent irradiation damage in the haematopoietic stem-cells of the mouse. The three following methodically differing arrangements were made: 1. 35 days after irradiation with 450 rad no difference is found between the measured turnover of incorporated 125 IUD in the bone marrow and not irradiated mice. However, there is a splenic cell population which unambiguously transfers its activity slowlier. A dose-response relationship exists to a limited extent. 2. By four transplantations at different instants the donors were marked first, and then the turnover of the early haematopoietic precursor cells in the bone marrow was detected. It resulted that 35 days after irradiation with 450 rad the turnover takes place slightly slowlier than in not irradiated early precursor cells. Iodised water, which is administered before the tracer technique is applied, seems to have a stimulating effect, particularly on the turnover of irradiated stem cells; the marking with a specific activity of 2000 Ci/mol seems to have a slightly toxic effect. 3. A test was developed, by which the proliferation velocity of stem cells and their descendants is measured when there is a very high proliferation stimulus. Differing amounts of bone marrow cells are transfused to lethally irradiated receivers. Within the logarithmic phase of the 125 IDU incorporation the relative cellular proliferation, originating in the stem cells being in the spleen, is determined for the interval between day 3 and day 5. It results very clearly that the descendants of those stem cells irradiated with 450 rad after a reconvalescence time of 35 days present a lower degree of rapid proliferative ability than the not irradiated cells. (orig./MG) [de

Preliminary observations on the correlation of proliferative phenomena with in vivo /sup 31/P NMR spectroscopy after tumor chemotherapy

International Nuclear Information System (INIS)

Schiffer, L.M.; Braunschweiger, P.G.; Glickson, J.D.; Evanochko, W.T.; Ng, T.C.

1985-01-01

In order to translate the concepts that have been developed in animal systems to human treatment programs, there is an urgent need for noninvasive techniques to study tumor cell biology. The characteristics of the ideal technique for the noninvasive monitoring of cell proliferation are truly imposing. The method should not require repeated biopsies; it should be amenable to repeated studies at frequent intervals without patient discomfort; it should monitor the proliferative response to the treatment modality; and it should not, in itself, perturb the tumor. Ideally, one would also like to be able to evaluate normal cell proliferation as well. It appears now that a new technique, /sup 31/P nuclear magnetic resonance (/sup 31/PNMR), may fulfill these rather rigid requirements. However, many studies in animal systems are necessary before it can be applied to the study of human tumors. The theory and mechanics of /sup 31/P NMR have been well described. Recently, its use as a noninvasive technique to study in vivo metabolic processes has become important. The authors presented a series of reports on the use of /sup 31/P NMR for the evaluation of tumor metabolism in animal systems under a variety of conditions. Studies of subcutaneously transplanted mouse tumors and human xenografts detected significant changes in nucleotide triphosphate (NTP), phosphocreatine, and inorganic phosphorus (Pi) as a result of tumor growth and perturbation with chemotherapeutic drugs, radiation, and hyperthermia. Their collabortive studies were designed to evaluate the changing effects of a noncurative single dose of cyclophosphamide on the /sup 31/P NMR resonances from the RIF-1 tumor, and to compare them with the proliferative changes that occur with time after drug administration. They were carried out in the hope of finding a noninvasive correlate with tumor cell proliferation

Herpes simplex virus (HSV)-specific proliferative and cytotoxic T-cell responses in humans immunized with an HSF type 2 glycoprotein subunit vaccine

Energy Technology Data Exchange (ETDEWEB)

Zarling, J.M.; Moran, P.A.; Brewer, L.; Ashley, R.; Corey, L.

1988-12-01

Studies were undertaken to determine whether immunization of humans with a herpes simplex virus type 2 (HSV-2) glycoprotein-subunit vaccine would result in the priming of both HSV-specific proliferating cells and cytotoxic T cells. Peripheral blood lymphocytes (PBL) from all eight vaccinees studied responded by proliferating after stimulation with HSV-2, HSV-1, and glycoprotein gB-1. The PBL of five of these eight vaccinees proliferated following stimulation with gD-2, whereas stimulation with Gd-1 resulted in relatively low or no proliferative responses. T-cell clones were generated from HSV-2-stimulated PBL of three vaccinees who demonstrated strong proliferative responses to HSV-1 and HSV-2. Of 12 clones studied in lymphoproliferative assays, 9 were found to be cross-reactive for HSV-1 and HSV-2. Of the approximately 90 T-cell clones isolated, 14 demonstrated HSV-specific cytotoxic activity. Radioimmunoprecipitation-polyacrylamide gel electrophoresis analyses confirmed that the vaccinees had antibodies only to HSV glycoproteins, not to proteins which are absent in the subunit vaccine, indicating that these vaccinees had not become infected with HSV. Immunization of humans with an HSV-2 glycoprotein-subunit vaccine thus results in the priming of T cells that proliferate in response to stimulation with HSV and its glycoproteins and T cells that have cytotoxic activity against HSV-infected cells. Such HSV-specific memory T cells were detected as late as 2 years following the last boost with the subunit vaccine.