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Sample records for arsenic-induced proliferative diseases

  1. 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.

  2. Proliferative and nonproliferative breast disease in atomic-bomb survivors

    International Nuclear Information System (INIS)

    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)

  3. Inheritance of proliferative breast disease in breast cancer kindreds

    International Nuclear Information System (INIS)

    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

  4. Role of mitochondria, ROS, and DNA damage in arsenic induced carcinogenesis.

    Science.gov (United States)

    Lee, Chih-Hung; Yu, Hsin-Su

    2016-01-01

    The International Agency for Research on Cancer (IARC) declared arsenic a class I carcinogen. Arsenic exposure induces several forms of human cancers, including cancers of skin, lung, liver, and urinary bladder. The majority of the arsenic-induced cancers occur in skin. Among these, the most common is Bowen's disease, characterized by epidermal hyperplasia, full layer epidermal dysplasia, leading to intraepidermal carcinoma as well as apoptosis, and moderate dermal infiltrates, which require the participation of mitochondria. The exact mechanism underlying arsenic induced carcinogenesis remains unclear, although increased reactive oxidative stresses, leading to chromosome abnormalities and uncontrolled growth, and aberrant immune regulations might be involved. Here, we highlight how increased mitochondrial biogenesis and oxidative stress lead to mitochondrial DNA damage and mutation in arsenic induced cancers. We also provide therapeutic rationale for targeting mitochondria in the treatment of arsenic induced cancers. PMID:27100709

  5. 3,3'-Diindolylmethane, a cruciferous vegetable derived synthetic anti-proliferative compound in thyroid disease

    International Nuclear Information System (INIS)

    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 IC50 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

  6. Proliferative kidney disease in brown trout – infection level, pathology and mortality under field conditions

    OpenAIRE

    Schmidt-Posthaus, Heike; Hirschi, Regula; Schneider, Ernst

    2015-01-01

    Proliferative kidney disease (PKD) is an emerging disease threatening wild salmonid populations. In temperature-controlled aquaria, PKD can cause mortality rates of up to 85% in rainbow trout. So far, no data about PKD-related mortality in wild brown trout Salmo trutta fario are available. The aim of this study was to investigate mortality rates and pathology in brown trout kept in a cage within a natural river habitat known to harbor Tetracapsuloides bryosalmonae. Young-of-the-year (YOY) ...

  7. Potential treatment of inflammatory and proliferative diseases by ultra-low doses of ionizing radiations.

    Science.gov (United States)

    Sanders, Charles L

    2012-12-01

    Ultra-low doses and dose- rates of ionizing radiation are effective in preventing disease which suggests that they also may be effective in treating disease. Limited experimental and anecdotal evidence indicates that low radiation doses from radon in mines and spas, thorium-bearing monazite sands and enhanced radioactive uranium ore obtained from a natural geological reactor may be useful in treating many inflammatory conditions and proliferative disorders, including cancer. Optimal therapeutic applications were identified via a literature survey as dose-rates ranging from 7 to 11μGy/hr or 28 to 44 times world average background rates. Rocks from an abandoned uranium mine in Utah were considered for therapeutic application and were examined by γ-ray and laser-induced breakdown fluorescence spectroscopy. The rocks showed the presence of transuranics and fission products with a γ-ray energy profile similar to aged spent uranium nuclear fuel (93% dose due to β particles and 7% due to γ rays). Mud packs of pulverized uranium ore rock dust in sealed plastic bags delivering bag surface β,γ dose-rates of 10-450 μGy/h were used with apparent success to treat several inflammatory and proliferative conditions in humans. PMID:23304108

  8. [The interpretation of immunophenotyping results during diagnostics of lymphatic proliferative disease using immunophenotyping count].

    Science.gov (United States)

    Isaeva, N V; Zaĭtseva, G A; Zagoskina, T P

    2013-02-01

    The article considers immune phenotyping heterogeneity of chronic lymphatic leukemia detected using basic diagnostic markers ofcell. The results of analysis of immune phenotypes of 108 patients with B-cell lymphatic proliferative diseases made it possible to establish that the atypical is related most rarely to indicators of expression of monotypic immunoglobulines and CD5 and most frequently to CD23, FMC7, CD22 and CS79b. During the present observation, the immune phenotyping count made up "3" or "2"points and the atypical alternative was registered among 10% of all examined patients with chronic lymphatic leukemia. It is demonstrated that patients with chronic lymphatic leukemia and with lower immune phenotyping count are characterized by major intensity of tumor substrate. PMID:23808007

  9. Proliferative kidney disease in brown trout: infection level, pathology and mortality under field conditions.

    Science.gov (United States)

    Schmidt-Posthaus, Heike; Hirschi, Regula; Schneider, Ernst

    2015-05-21

    Proliferative kidney disease (PKD) is an emerging disease threatening wild salmonid populations. In temperature-controlled aquaria, PKD can cause mortality rates of up to 85% in rainbow trout. So far, no data about PKD-related mortality in wild brown trout Salmo trutta fario are available. The aim of this study was to investigate mortality rates and pathology in brown trout kept in a cage within a natural river habitat known to harbor Tetracapsuloides bryosalmonae. Young-of-the-year (YOY) brown trout, free of T. bryosalmonae, were exposed in the River Wutach, in the northeast of Switzerland, during 3 summer months. Samples of wild brown trout caught by electrofishing near the cage location were examined in parallel. The incidence of PKD in cage-exposed animals (69%) was not significantly different to the disease prevalence of wild fish (82 and 80% in the upstream and downstream locations, respectively). The mortality in cage-exposed animals, however, was as low as 15%. At the termination of the exposure experiment, surviving fish showed histological lesions typical for PKD regression, suggesting that many YOY brown trout survive the initial infection. Our results at the River Wutach suggest that PKD in brown trout does not always result in high mortality under natural conditions. PMID:25993888

  10. Arsenic induces apoptosis in mouse liver is mitochondria dependent and is abrogated by N-acetylcysteine

    International Nuclear Information System (INIS)

    Arsenicosis, caused by arsenic contamination of drinking water supplies, is a major public health problem in India and Bangladesh. Chronic liver disease, often with portal hypertension occurs in chronic arsenicosis, contributes to the morbidity and mortality. The early cellular events that initiate liver cell injury due to arsenicosis have not been studied. Our aim was to identify the possible mechanisms related to arsenic-induced liver injury in mice. Liver injury was induced in mice by arsenic treatment. The liver was used for mitochondrial oxidative stress, mitochondrial permeability transition (MPT). Evidence of apoptosis was sought by TUNEL test, caspase assay and histology. Pretreatment with N-acetyl-L-cysteine (NAC) was done to modulate hepatic GSH level. Arsenic treatment in mice caused liver injury associated with increased oxidative stress in liver mitochondria and alteration of MPT. Altered MPT facilitated cytochrome c release in the cytosol, activation of caspase 9 and caspase 3 activities and apoptotic cell death. Pretreatment of NAC to arsenic-treated mice abrogated all these alteration suggesting a glutathione (GSH)-dependent mechanism. Oxidative stress in mitochondria and inappropriate MPT are important in the pathogenesis of arsenic induced apoptotic liver cell injury. The phenomenon is GSH dependent and supplementation of NAC might have beneficial effects

  11. Severe proliferative retinopathy is associated with blood hyperviscosity in sickle cell hemoglobin-C disease but not in sickle cell anemia. : Sickle cell disease and retinopathy

    OpenAIRE

    Lemaire, Clément; Lamarre, Yann; Lemonne, Nathalie; Waltz, Xavier; Chahed, Sadri; Cabot, Florence; Botez, Ioana; Tressieres, Benoit; Lalanne-Mistrih, Marie-Laure; Etienne-Julan, Maryse; Connes, Philippe

    2012-01-01

    International audience Little is known about the impact of blood rheology on the occurrence of retinopathy in sickle cell disease (SCD). Fifty-nine adult SCD patients in steady-state condition participated to the study: 32 with homozygous SCD (sickle cell anemia; SCA) and 27 with sickle cell hemoglobin-C disease (SCC). The patients underwent retinal examination and were categorized according to the classification of Goldberg: 1) no retinopathy (group 1), 2) non-proliferative or proliferati...

  12. Arsenic Induced Decreases in the Vascular Matrix

    OpenAIRE

    Hays, Allison M.; Lantz, R. Clark; Rodgers, Laurel S.; Sollome, James J.; Vaillancourt, Richard R.; Andrew, Angeline S; Hamilton, Joshua W.; Camenisch, Todd D.

    2008-01-01

    Chronic ingestion of arsenic is associated with increased incidence of respiratory and cardiovascular diseases. To investigate the role of arsenic in early events in vascular pathology, C57BL/6 mice ingested drinking water with or without 50 ppb sodium arsenite (AsIII) for four, five or eight weeks. At five and eight weeks, RNA from the lungs of control and AsIII exposed animals was processed for microarray. Sixty-five genes were significantly and differentially expressed. Differential expres...

  13. Arsenic-Induced Genotoxicity and Genetic Susceptibility to Arsenic-Related Pathologies

    Directory of Open Access Journals (Sweden)

    Fabrizio Bianchi

    2013-04-01

    Full Text Available The arsenic (As exposure represents an important problem in many parts of the World. Indeed, it is estimated that over 100 million individuals are exposed to arsenic, mainly through a contamination of groundwaters. Chronic exposure to As is associated with adverse effects on human health such as cancers, cardiovascular diseases, neurological diseases and the rate of morbidity and mortality in populations exposed is alarming. The purpose of this review is to summarize the genotoxic effects of As in the cells as well as to discuss the importance of signaling and repair of arsenic-induced DNA damage. The current knowledge of specific polymorphisms in candidate genes that confer susceptibility to arsenic exposure is also reviewed. We also discuss the perspectives offered by the determination of biological markers of early effect on health, incorporating genetic polymorphisms, with biomarkers for exposure to better evaluate exposure-response clinical relationships as well as to develop novel preventative strategies for arsenic- health effects.

  14. Arsenic-induced Aurora-A activation contributes to chromosome instability and tumorigenesis

    Science.gov (United States)

    Wu, Chin-Han; Tseng, Ya-Shih; Yang, Chao-Chun; Kao, Yu-Ting; Sheu, Hamm-Ming; Liu, Hsiao-Sheng

    2013-11-01

    Arsenic may cause serious environmental pollution and is a serious industrial problem. Depending on the dosage, arsenic may trigger the cells undergoing either proliferation or apoptosis-related cell death. Because of lack of the proper animal model to study arsenic induced tumorigenesis, the accurate risk level of arsenic exposure has not been determined. Arsenic shows genotoxic effect on human beings who uptake water contaminated by arsenic. Chromosome aberration is frequently detected in arsenic exposure-related diseases and is associated with increased oxidative stress and decreased DNA repairing activity, but the underlying mechanism remains elusive. Aurora-A is a mitotic kinase, over-expression of Aurora-A leads to centrosome amplification, chromosomal instability and cell transformation. We revealed that Aurora-A is over-expressed in the skin and bladder cancer patients from blackfoot-disease endemic areas. Our cell line studies reveal that arsenic exposure between 0.5 μM and 1 μM for 2-7 days are able to induce Aurora-A expression and activation based on promoter activity, RNA and protein analysis. Aurora-A overexpression further increases the frequency of unsymmetrical chromosome segregation through centrosome amplification followed by cell population accumulated at S phase in immortalized keratinocyte (HaCaT) and uroepithelial cells (E7). Furthermore, Aurora-A over-expression was sustained for 1-4 weeks by chronic treatment of immortalized bladder and skin cells with NaAsO2. Aurora-A promoter methylation and gene amplification was not detected in the long-term arsenic treated E7 cells. Furthermore, the expression level of E2F1 transcription factor (E2F1) is increased in the presence of arsenic, and arsenic-related Aurora-A over-expression is transcriptionally regulated by E2F1. We further demonstrated that overexpression of Aurora-A and mutant Ha-ras or Aurora-A and mutant p53 may act additively to trigger arsenic-related bladder and skin cancer

  15. Atorvastatin ameliorates arsenic-induced hypertension and enhancement of vascular redox signaling in rats

    Energy Technology Data Exchange (ETDEWEB)

    Sarath, Thengumpallil Sasindran; Waghe, Prashantkumar; Gupta, Priyanka; Choudhury, Soumen; Kannan, Kandasamy [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Pillai, Ayyappan Harikrishna [Division of Animal Biochemistry, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Harikumar, Sankaran Kutty; Mishra, Santosh Kumar [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Sarkar, Souvendra Nath, E-mail: snsarkar1911@rediffmail.com [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India)

    2014-11-01

    Chronic arsenic exposure has been linked to elevated blood pressure and cardiovascular diseases, while statins reduce the incidence of cardiovascular disease predominantly by their low density lipoprotein-lowering effect. Besides, statins have other beneficial effects, including antioxidant and anti-inflammatory activities. We evaluated whether atorvastatin, a widely used statin, can ameliorate arsenic-induced increase in blood pressure and alteration in lipid profile and also whether the amelioration could relate to altered NO and ROS signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91st day, blood was collected for lipid profile. Western blot of iNOS and eNOS protein, NO and 3-nitrotyrosine production, Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation, lipid peroxidation and antioxidants were evaluated in thoracic aorta. Arsenic increased systolic, diastolic and mean arterial blood pressure, while it decreased HDL-C and increased LDL-C, total cholesterol and triglycerides in serum. Arsenic down-regulated eNOS and up-regulated iNOS protein expression and increased basal NO and 3-nitrotyrosine level. Arsenic increased aortic Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation and lipid peroxidation. Further, arsenic decreased the activities of superoxide dismutase, catalase, and glutathione peroxidase and depleted aortic GSH content. Atorvastatin regularized blood pressure, improved lipid profile and attenuated arsenic-mediated redox alterations. The results demonstrate that atorvastatin has the potential to ameliorate arsenic-induced hypertension by improving lipid profile, aortic NO signaling and restoring vascular redox homeostasis. - Highlights: • Arsenic increased systolic, diastolic and mean arterial blood pressure and caused dyslipidemia. • Arsenic increased

  16. Atorvastatin ameliorates arsenic-induced hypertension and enhancement of vascular redox signaling in rats

    International Nuclear Information System (INIS)

    Chronic arsenic exposure has been linked to elevated blood pressure and cardiovascular diseases, while statins reduce the incidence of cardiovascular disease predominantly by their low density lipoprotein-lowering effect. Besides, statins have other beneficial effects, including antioxidant and anti-inflammatory activities. We evaluated whether atorvastatin, a widely used statin, can ameliorate arsenic-induced increase in blood pressure and alteration in lipid profile and also whether the amelioration could relate to altered NO and ROS signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91st day, blood was collected for lipid profile. Western blot of iNOS and eNOS protein, NO and 3-nitrotyrosine production, Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation, lipid peroxidation and antioxidants were evaluated in thoracic aorta. Arsenic increased systolic, diastolic and mean arterial blood pressure, while it decreased HDL-C and increased LDL-C, total cholesterol and triglycerides in serum. Arsenic down-regulated eNOS and up-regulated iNOS protein expression and increased basal NO and 3-nitrotyrosine level. Arsenic increased aortic Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation and lipid peroxidation. Further, arsenic decreased the activities of superoxide dismutase, catalase, and glutathione peroxidase and depleted aortic GSH content. Atorvastatin regularized blood pressure, improved lipid profile and attenuated arsenic-mediated redox alterations. The results demonstrate that atorvastatin has the potential to ameliorate arsenic-induced hypertension by improving lipid profile, aortic NO signaling and restoring vascular redox homeostasis. - Highlights: • Arsenic increased systolic, diastolic and mean arterial blood pressure and caused dyslipidemia. • Arsenic increased

  17. Atorvastatin restores arsenic-induced vascular dysfunction in rats: Modulation of nitric oxide signaling and inflammatory mediators

    International Nuclear Information System (INIS)

    We evaluated whether atorvastatin, an extensively prescribed statin for reducing the risks of cardiovascular diseases, can reduce the risk of arsenic-induced vascular dysfunction and inflammation in rats and whether the modulation could be linked to improvement in vascular NO signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91st day, blood was collected for measuring serum C-reactive protein. Thoracic aorta was isolated for assessing reactivity to phenylephrine, sodium nitroprusside and acetylcholine; evaluating eNOS and iNOS mRNA expression and measuring NO production, while abdominal aorta was used for ELISA of cytokines, chemokine and vascular cell adhesion molecules. Histopathology was done in aortic arches. Arsenic did not alter phenylephrine-elicited contraction. Atorvastatin inhibited Emax of phenylephrine, but it augmented the contractile response in aortic rings from arsenic-exposed animals. Sodium nitroprusside-induced relaxation was not altered with any treatment. However, arsenic reduced acetylcholine-induced relaxation and affected aortic eNOS at the levels of mRNA expression, protein concentration, phosphorylation and NO production. Further, it increased aortic iNOS mRNA expression, iNOS-derived NO synthesis, production of pro-inflammatory mediators (IL-1β, IL-6, MCP-1, VCAM, sICAM) and serum C-reactive protein and aortic vasculopathic lesions. Atorvastatin attenuated these arsenic-mediated functional, biochemical and structural alterations. Results show that atorvastatin has the potential to ameliorate arsenic-induced vascular dysfunction and inflammation by restoring endothelial function with improvement in NO signaling and attenuating production of pro-inflammatory mediators and cell adhesion molecules. - Highlights: • We evaluated if atorvastatin reduce arsenic-induced

  18. Atorvastatin restores arsenic-induced vascular dysfunction in rats: Modulation of nitric oxide signaling and inflammatory mediators

    Energy Technology Data Exchange (ETDEWEB)

    Kesavan, Manickam; Sarath, Thengumpallil Sasindran; Kannan, Kandasamy; Suresh, Subramaniyam; Gupta, Priyanka; Vijayakaran, Karunakaran; Sankar, Palanisamy; Kurade, Nitin Pandurang; Mishra, Santosh Kumar; Sarkar, Souvendra Nath, E-mail: snsarkar1911@rediffmail.com

    2014-10-01

    We evaluated whether atorvastatin, an extensively prescribed statin for reducing the risks of cardiovascular diseases, can reduce the risk of arsenic-induced vascular dysfunction and inflammation in rats and whether the modulation could be linked to improvement in vascular NO signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91{sup st} day, blood was collected for measuring serum C-reactive protein. Thoracic aorta was isolated for assessing reactivity to phenylephrine, sodium nitroprusside and acetylcholine; evaluating eNOS and iNOS mRNA expression and measuring NO production, while abdominal aorta was used for ELISA of cytokines, chemokine and vascular cell adhesion molecules. Histopathology was done in aortic arches. Arsenic did not alter phenylephrine-elicited contraction. Atorvastatin inhibited E{sub max} of phenylephrine, but it augmented the contractile response in aortic rings from arsenic-exposed animals. Sodium nitroprusside-induced relaxation was not altered with any treatment. However, arsenic reduced acetylcholine-induced relaxation and affected aortic eNOS at the levels of mRNA expression, protein concentration, phosphorylation and NO production. Further, it increased aortic iNOS mRNA expression, iNOS-derived NO synthesis, production of pro-inflammatory mediators (IL-1β, IL-6, MCP-1, VCAM, sICAM) and serum C-reactive protein and aortic vasculopathic lesions. Atorvastatin attenuated these arsenic-mediated functional, biochemical and structural alterations. Results show that atorvastatin has the potential to ameliorate arsenic-induced vascular dysfunction and inflammation by restoring endothelial function with improvement in NO signaling and attenuating production of pro-inflammatory mediators and cell adhesion molecules. - Highlights: • We evaluated if atorvastatin reduce arsenic-induced

  19. The potential biological mechanisms of arsenic-induced diabetes mellitus

    International Nuclear Information System (INIS)

    Although epidemiologic studies carried out in Taiwan, Bangladesh, and Sweden have demonstrated a diabetogenic effect of arsenic, the mechanisms remain unclear and require further investigation. This paper reviewed the potential biological mechanisms of arsenic-induced diabetes mellitus based on the current knowledge of the biochemical properties of arsenic. Arsenate can substitute phosphate in the formation of adenosine triphosphate (ATP) and other phosphate intermediates involved in glucose metabolism, which could theoretically slow down the normal metabolism of glucose, interrupt the production of energy, and interfere with the ATP-dependent insulin secretion. However, the concentration of arsenate required for such reaction is high and not physiologically relevant, and these effects may only happen in acute intoxication and may not be effective in subjects chronically exposed to low-dose arsenic. On the other hand, arsenite has high affinity for sulfhydryl groups and thus can form covalent bonds with the disulfide bridges in the molecules of insulin, insulin receptors, glucose transporters (GLUTs), and enzymes involved in glucose metabolism (e.g., pyruvate dehydrogenase and α-ketoglutarate dehydrogenase). As a result, the normal functions of these molecules can be hampered. However, a direct effect on these molecules caused by arsenite at physiologically relevant concentrations seems unlikely. Recent evidence has shown that treatment of arsenite at lower and physiologically relevant concentrations can stimulate glucose transport, in contrary to an inhibitory effect exerted by phenylarsine oxide (PAO) or by higher doses of arsenite. Induction of oxidative stress and interferences in signal transduction or gene expression by arsenic or by its methylated metabolites are the most possible causes to arsenic-induced diabetes mellitus through mechanisms of induction of insulin resistance and β cell dysfunction. Recent studies have shown that, in subjects with chronic

  20. Unraveling the mechanism of neuroprotection of curcumin in arsenic induced cholinergic dysfunctions in rats

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, Pranay [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Yadav, Rajesh S. [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Department of Crimnology and Forensic Science, Harisingh Gour University, Sagar 470 003 (India); Chandravanshi, Lalit P.; Shukla, Rajendra K.; Dhuriya, Yogesh K.; Chauhan, Lalit K.S. [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Dwivedi, Hari N. [Babu Banarasi Das University, BBD City, Faizabad Road, Lucknow 227 015 (India); Pant, Aditiya B. [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Khanna, Vinay K., E-mail: vkkhanna1@gmail.com [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India)

    2014-09-15

    Earlier, we found that arsenic induced cholinergic deficits in rat brain could be protected by curcumin. In continuation to this, the present study is focused to unravel the molecular mechanisms associated with the protective efficacy of curcumin in arsenic induced cholinergic deficits. Exposure to arsenic (20 mg/kg body weight, p.o) for 28 days in rats resulted to decrease the expression of CHRM2 receptor gene associated with mitochondrial dysfunctions as evident by decrease in the mitochondrial membrane potential, activity of mitochondrial complexes and enhanced apoptosis both in the frontal cortex and hippocampus in comparison to controls. The ultrastructural images of arsenic exposed rats, assessed by transmission electron microscope, exhibited loss of myelin sheath and distorted cristae in the mitochondria both in the frontal cortex and hippocampus as compared to controls. Simultaneous treatment with arsenic (20 mg/kg body weight, p.o) and curcumin (100 mg/kg body weight, p.o) for 28 days in rats was found to protect arsenic induced changes in the mitochondrial membrane potential and activity of mitochondrial complexes both in frontal cortex and hippocampus. Alterations in the expression of pro- and anti-apoptotic proteins and ultrastructural damage in the frontal cortex and hippocampus following arsenic exposure were also protected in rats simultaneously treated with arsenic and curcumin. The data of the present study reveal that curcumin could protect arsenic induced cholinergic deficits by modulating the expression of pro- and anti-apoptotic proteins in the brain. More interestingly, arsenic induced functional and ultrastructural changes in the brain mitochondria were also protected by curcumin. - Highlights: • Neuroprotective mechanism of curcumin in arsenic induced cholinergic deficits studied • Curcumin protected arsenic induced enhanced expression of stress markers in rat brain • Arsenic compromised mitochondrial electron transport chain protected

  1. Unraveling the mechanism of neuroprotection of curcumin in arsenic induced cholinergic dysfunctions in rats

    International Nuclear Information System (INIS)

    Earlier, we found that arsenic induced cholinergic deficits in rat brain could be protected by curcumin. In continuation to this, the present study is focused to unravel the molecular mechanisms associated with the protective efficacy of curcumin in arsenic induced cholinergic deficits. Exposure to arsenic (20 mg/kg body weight, p.o) for 28 days in rats resulted to decrease the expression of CHRM2 receptor gene associated with mitochondrial dysfunctions as evident by decrease in the mitochondrial membrane potential, activity of mitochondrial complexes and enhanced apoptosis both in the frontal cortex and hippocampus in comparison to controls. The ultrastructural images of arsenic exposed rats, assessed by transmission electron microscope, exhibited loss of myelin sheath and distorted cristae in the mitochondria both in the frontal cortex and hippocampus as compared to controls. Simultaneous treatment with arsenic (20 mg/kg body weight, p.o) and curcumin (100 mg/kg body weight, p.o) for 28 days in rats was found to protect arsenic induced changes in the mitochondrial membrane potential and activity of mitochondrial complexes both in frontal cortex and hippocampus. Alterations in the expression of pro- and anti-apoptotic proteins and ultrastructural damage in the frontal cortex and hippocampus following arsenic exposure were also protected in rats simultaneously treated with arsenic and curcumin. The data of the present study reveal that curcumin could protect arsenic induced cholinergic deficits by modulating the expression of pro- and anti-apoptotic proteins in the brain. More interestingly, arsenic induced functional and ultrastructural changes in the brain mitochondria were also protected by curcumin. - Highlights: • Neuroprotective mechanism of curcumin in arsenic induced cholinergic deficits studied • Curcumin protected arsenic induced enhanced expression of stress markers in rat brain • Arsenic compromised mitochondrial electron transport chain protected

  2. Arsenic-induced SUMO-dependent recruitment of RNF4 into PML nuclear bodies.

    Science.gov (United States)

    Geoffroy, Marie-Claude; Jaffray, Ellis G; Walker, Katherine J; Hay, Ronald T

    2010-12-01

    In acute promyelocytic leukemia (APL), the promyelocytic leukemia (PML) protein is fused to the retinoic acid receptor alpha (RAR). Arsenic is an effective treatment for this disease as it induces SUMO-dependent ubiquitin-mediated proteasomal degradation of the PML-RAR fusion protein. Here we analyze the nuclear trafficking dynamics of PML and its SUMO-dependent ubiquitin E3 ligase, RNF4 in response to arsenic. After administration of arsenic, PML immediately transits into nuclear bodies where it undergoes SUMO modification. This initial recruitment of PML into nuclear bodies is not dependent on RNF4, but RNF4 quickly follows PML into the nuclear bodies where it is responsible for ubiquitylation of SUMO-modified PML and its degradation by the proteasome. While arsenic restricts the mobility of PML, FRAP analysis indicates that RNF4 continues to rapidly shuttle into PML nuclear bodies in a SUMO-dependent manner. Under these conditions FRET studies indicate that RNF4 interacts with SUMO in PML bodies but not directly with PML. These studies indicate that arsenic induces the rapid reorganization of the cell nucleus by SUMO modification of nuclear body-associated PML and uptake of the ubiquitin E3 ligase RNF4 leading to the ubiquitin-mediated degradation of PML. PMID:20943951

  3. FoxO1a and SIRT1 in vasculo-proliferative diseases : Major roles in regulating smooth muscle cell proliferation, migration and survival

    OpenAIRE

    König, Heike

    2009-01-01

    Vasculo-proliferative disorders such as atherosclerosis, postangioplasty restenosis, and pulmonary hypertension are complex processes that are especially related to vascular smooth muscle cells (VSMCs)45, 78. In the arterial media, VSMC are normally quiescent, however, for the development and progression of the above mentioned diseases it is prerequisite that quiescent VSMCs start to proliferate, migrate and undergo apoptosis. Different extracellular stimuli are responsible for regulating VSM...

  4. First Proliferative Kidney Disease outbreak in Austria, linking to the aetiology of Black Trout Syndrome threatening autochthonous trout populations.

    Science.gov (United States)

    Gorgoglione, Bartolomeo; Kotob, Mohamed H; Unfer, Günter; El-Matbouli, Mansour

    2016-05-01

    Proliferative Kidney Disease (PKD) was diagnosed in juvenile autochthonous brown trout Salmo trutta for the first time in Austria during summer 2014. Cytology showed Tetracapsuloides bryosalmonae sporoblasts, and histology revealed sporogonic (coelozoic) and extrasporogonic (histozoic) stages. Analysis of malacosporean ribosomal small subunit revealed that this strain is closely related to European isolates, although its source is unknown. Infection and high pathogenicity were reproduced upon a pre-restocking test with specific pathogen free (SPF) juvenile trout, resulting in 100% mortality between 28 and 46 d post exposure (dpe), with high ectoparasitosis. Fish showed grade 2 of the Kidney Swelling Index and grade 3 of the PKD histological assessment. T. bryosalmonae enzootic waters were demonstrated in further locations along the River Kamp, with infected bryozoans retrieved up to 6 km upstream of the farm with the PKD outbreak. Fredericella sultana colonies collected from these locations were cultivated in laboratory conditions. Released malacospores successfully induced PKD, and contextually Black Trout Syndrome (BTS), in SPF brown trout. In the absence of co-infections mortality occurred between 59 and 98 dpe, with kidneys enlarged up to 6.74% of total body weight (normal 1.23%). This study confirms the first isolation of a pathogenic myxozoan from an Austrian river tributary of the Danube, where its 2-host life cycle is fully occurring. Its immunosuppressant action could link PKD as a key factor in the multifactorial aetiology of BTS. This T. bryosalmonae isolation provides an impetus to undertake further multi-disciplinary research, aiming to assess the impact of PKD and BTS spreading to central European regions. PMID:27137070

  5. Protective effects of Moringa oleifera Lam. leaves against arsenic-induced toxicity in mice

    Institute of Scientific and Technical Information of China (English)

    Afzal Sheikh; Zahangir Alam Saud; Khaled Hossain; Fouzia Yeasmin; Smita Agarwal; Mashiur Rahman; Khairul Islam; Ekhtear Hossain; Shakhawoat Hossain; Md Rezaul Karim; Farjana Nikkon

    2014-01-01

    Objective: To evaluate the protective role of leaves of Moringa oleifera (M. oleifera) Lam. against arsenic-induced toxicity in mice.Methods:non-treated control group while, the second, third, and fourth groups were treated with M.oleifera leaves (50 mg/kg body weight per day), sodium arsenite (10 mg/kg body weight per day) and sodium arsenite plus M. oleifera leaves, respectively. Serum indices related to cardiac, liver and renal functions were analyzed to evaluate the protective effect of Moringa leaves on arsenic-induced effects in mice.Results:Swiss albino male mice were divided into four groups. The first group was used as induced elevation of triglyceride, glucose, urea and the activities of alkaline phospatase, aspartate aminotransferase and alanine aminotransferase in serum. M. oleifera leaves also prevented the arsenic-induced perturbation of serum butyryl cholinesterase activity, total cholesterol and high density lipoprotein cholesterol.Conclusions:The results indicate that the leaves of M. oleifera may be useful in reducing the It revealed that food supplementation of M. oleifera leaves abrogated the arsenic-effects of arsenic-induced toxicity.

  6. Beta-amyloid peptides enhance the proliferative response of activated CD4CD28 lymphocytes from Alzheimer disease patients and from healthy elderly.

    Directory of Open Access Journals (Sweden)

    Agnieszka Jóźwik

    Full Text Available Alzheimer's disease (AD is the most frequent form of dementia among elderly. Despite the vast amount of literature on non-specific immune mechanisms in AD there is still little information about the potential antigen-specific immune response in this pathology. It is known that early stages of AD include β-amyloid (Aβ- reactive antibodies production and inflammatory response. Despite some evidence gathered proving cellular immune response background in AD pathology, the specific reactions of CD4(+ and CD8(+ cells remain unknown as the previous investigations yielded conflicting results. Here we investigated the CD4(+CD28(+ population of human peripheral blood T cells and showed that soluble β-amyloids alone were unable to stimulate these cells to proliferate significantly, resulting only in minor, probably antigen-specific, proliferative response. On the other hand, the exposure of in vitro pre-stimulated lymphocytes to soluble Aβ peptides significantly enhanced the proliferative response of these cells which had also lead to increased levels of TNF, IL-10 and IL-6. We also proved that Aβ peptide-enhanced proliferative response of CD4(+CD28(+ cells is autonomous and independent from disease status while being associated with the initial, ex vivo activation status of the CD4(+ cells. In conclusion, we suggest that the effect of Aβ peptides on the immune system of AD patients does not depend on the specific reactivity to Aβ epitope(s, but is rather a consequence of an unspecific modulation of the cell cycle dynamics and cytokine production by T cells, occurring simultaneously in a huge proportion of Aβ peptide-exposed T lymphocytes and affecting the immune system performance.

  7. 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)

    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

  8. Association of arsenic-induced malignant transformation with DNA hypomethylation and aberrant gene expression

    OpenAIRE

    Zhao, Christopher Q.; Young, Matthew R.; Diwan, Bhalchandra A.; Coogan, Timothy P.; Waalkes, Michael P.

    1997-01-01

    Inorganic arsenic, a human carcinogen, is enzymatically methylated for detoxication, consuming S-adenosyl-methionine (SAM) in the process. The fact that DNA methyltransferases (MeTases) require this same methyl donor suggests a role for methylation in arsenic carcinogenesis. Here we test the hypothesis that arsenic-induced initiation results from DNA hypomethylation caused by continuous methyl depletion. The hypothesis was tested by first inducing transformation in a rat liver epithelial cell...

  9. Therapeutic effects of Moringa oleifera on arsenic-induced toxicity in rats.

    Science.gov (United States)

    Gupta, Richa; Kannan, Gurusamy M; Sharma, Mamta; S Flora, Swaran J

    2005-11-01

    the seed powder of M. oleifera has significant role in protecting animals from arsenic-induced oxidative stress and in the depletion of arsenic concentration. Further studies thus can be recommended for determining the effect of co-administrating seed powder of M. oleifera during chelation therapy with a thiol chelator. PMID:21783626

  10. Arsenic-induced anti-angiogenesis via miR-425-5p-regulated CCM3.

    Science.gov (United States)

    Gao, Yanfang; Yin, Yuzhu; Xing, Xiumei; Zhao, Zhiqiang; Lu, Yao; Sun, Yi; Zhuang, Zhixiong; Wang, Min; Ji, Weidong; He, Yun

    2016-07-01

    Human exposure to drinking water contaminated with arsenic is a serious global health concern and it predisposes people to cardiovascular diseases, such as hypertension, atherosclerosis, and microvascular diseases. Although accumulating evidence supports a role for angiogenesis responses to arsenic in the pathogenesis of the cardiovascular disease, the detailed molecular mechanism is not well understood. We aimed to determine the role and mechanism of microRNA (miRNA) in arsenic-induced angiogenesis. In our present study, sodium arsenite (NaAsO2) inhibited angiogenesis by decreasing cells proliferation, migration and tube formation in HUVECs. After NaAsO2 treatment, we found the expression of microRNA-425-5p (miR-425-5p) was reduced in vitro and in vivo and over-expression of miR-425-5p reversed the NaAsO2-induced anti-angiogenesis through its direct target cerebral cavernous malformation 3 (CCM3). Furthermore, we showed that NaAsO2 up-regulated CCM3 expression in vitro and in vivo. In addition, we demonstrated that inhibition of Notch and activation of VEGF/p38 signaling were involved in miR-425-5p blocking NaAsO2-induced anti-angiogenesis. PMID:27132035

  11. Molecular basis for arsenic-Induced alteration in nitric oxide production and oxidative stress: implication of endothelial dysfunction

    International Nuclear Information System (INIS)

    Accumulated epidemiological studies have suggested that prolonged exposure of humans to arsenic in drinking water is associated with vascular diseases. The exact mechanism of how this occurs currently unknown. Nitric oxide (NO), formed by endothelial NO synthase (eNOS), plays a crucial role in the vascular system. Decreased availability of biologically active NO in the endothelium is implicated in the pathophysiology of several vascular diseases and inhibition of eNOS by arsenic is one of the proposed mechanism s for arsenic-induced vascular diseases. In addition, during exposure to arsenic, overproduction of reactive oxygen species (ROS) can occur, resulting in oxidative stress, which is another major risk factor for vascular dysfunction. The molecular basis for decreased NO levels and increased oxidative stress during arsenic exposure is poorly understood. In this article, evidence for arsenic-mediated alteration in NO production and oxidative stress is reviewed. The results of a cross-sectional study in an endemic area of chronic arsenic poisoning and experimental animal studies to elucidate a potential mechanism for the impairment of NO formation and oxidative stress caused by prolonged exposure to arsenate in the drinking water are also reviewed

  12. Discovery of a gamma heavy chain disease in a patient followed-up for a lymphoplasma cell proliferative disorder.

    Science.gov (United States)

    Humeau, Camille; Monjanel, Hélène; Schellenberg, François

    2016-06-01

    Gamma-heavy chains disease is a rare disease, with very few cases described in the literature. It is characterized by the presence of a monoclonal gamma-heavy chain without associated light chain. Its prevalence and prognosis are unknown. We report here the accidental discovery of a case of gamma-heavy chain disease during a pancytopenia exploration, performed in the hospital, in a patient known since 2002 for a lymphoplasmacytic type lymphoma first localized in bone marrow. PMID:27237805

  13. Arsenic-induced alteration in intracellular calcium homeostasis induces head kidney macrophage apoptosis involving the activation of calpain-2 and ERK in Clarias batrachus

    International Nuclear Information System (INIS)

    We had earlier shown that exposure to arsenic (0.50 μM) caused caspase-3 mediated head kidney macrophage (HKM) apoptosis involving the p38-JNK pathway in Clarias batrachus. Here we examined the roles of calcium (Ca2+) and extra-cellular signal-regulated protein kinase (ERK), the other member of MAPK-pathway on arsenic-induced HKM apoptosis. Arsenic-induced HKM apoptosis involved increased expression of ERK and calpain-2. Nifedipine, verapamil and EGTA pre-treatment inhibited the activation of calpain-2, ERK and reduced arsenic-induced HKM apoptosis as evidenced from reduced caspase-3 activity, Annexin V-FITC-propidium iodide and Hoechst 33342 staining. Pre-incubation with ERK inhibitor U 0126 inhibited the activation of calpain-2 and interfered with arsenic-induced HKM apoptosis. Additionally, pre-incubation with calpain-2 inhibitor also interfered with the activation of ERK and inhibited arsenic-induced HKM apoptosis. The NADPH oxidase inhibitor apocynin and diphenyleneiodonium chloride also inhibited ERK activation indicating activation of ERK in arsenic-exposed HKM also depends on signals from NADPH oxidase pathway. Our study demonstrates the critical role of Ca2+ homeostasis on arsenic-induced HKM apoptosis. We suggest that arsenic-induced alteration in intracellular Ca2+ levels initiates pro-apoptotic ERK and calpain-2; the two pathways influence each other positively and induce caspase-3 mediated HKM apoptosis. Besides, our study also indicates the role of ROS in the activation of ERK pathway in arsenic-induced HKM apoptosis in C. batrachus. - Highlights: → Altered Ca2+ homeostasis leads to arsenic-induced HKM apoptosis. → Calpain-2 plays a critical role in the process. → ERK is pro-apoptotic in arsenic-induced HKM apoptosis. → Arsenic-induced HKM apoptosis involves cross talk between calpain-2 and ERK.

  14. Enhanced protective activity of nano formulated andrographolide against arsenic induced liver damage.

    Science.gov (United States)

    Das, Sujata; Pradhan, Goutam Kumar; Das, Subhadip; Nath, Debjani; Das Saha, Krishna

    2015-12-01

    Chronic exposure to arsenic over a period of time induces toxicity, primarily in liver but gradually in all systems of the body. Andrographolide (AG), a major diterpene lactone of Andrographis paniculata, shows a wide array of physiological functions including hepatoprotection. Therapeutic applications of AG are however seriously constrained because of its insolubility, poor bioavailability, and short plasma half-life. Nanoparticulation of AG is a possible solution to these problems. In the present study we investigated the effectiveness of polylactide co-glycolide (PLGA) nanocapsulated andrographolide (NA) against arsenic induced liver damage in mice. NA of average diameter 65.8 nm and encapsulation efficiency of 64% were prepared. Sodium arsenite at a dose of 40 mg/L supplied via drinking water in mice significantly raised the serum level of liver function markers such as AST, ALT, and ALP, and caused arsenic deposition in liver and ROS generation, though it did not show any lethality up to 30 days of exposure. However, even liver toxicity was not observed when mice were given AG and NA orally at doses up to 100 mg/kg bwt and 20 mg/kg bwt respectively on alternate days for one month. Treatment of non-toxic doses of AG or NA on alternate days along with arsenic significantly decreased the arsenic induced elevation of the serum level of ALT, AST and ALP, and arsenic deposition in liver. AG and NA increased the level of hepatic antioxidant enzymes such as superoxide dismutase (SOD), and catalase (CAT), and the level of reduced glutathione (GSH). Also, the ROS level was lowered in mice exposed to arsenic but treated with AG or NA. Protective efficiency of NA is about five times more than that of AG. Administration of NA to arsenic-treated mice caused signs of improvement in liver tissue architecture. In conclusion, the results of this study suggest that NA could be beneficial against arsenic-induced liver toxicity. PMID:26485141

  15. Arsenic-induced oxidative myocardial injury: protective role of arjunolic acid

    Energy Technology Data Exchange (ETDEWEB)

    Manna, Prasenjit; Sinha, Mahua; Sil, Parames C. [Bose Institute, Department of Chemistry, Kolkata, West Bengal (India)

    2008-03-15

    Arsenic, one of the most harmful metalloids, is ubiquitous in the environment. The present study has been carried out to investigate the protective role of a triterpenoid saponin, arjunolic acid (AA) against arsenic-induced cardiac oxidative damage. In the study, NaAsO{sub 2} was chosen as the source of arsenic. The free radical scavenging activity and the effect of AA on the intracellular antioxidant power were determined from its 2,2-diphenyl-1-picryl hydrazyl radical scavenging ability and ferric reducing/antioxidant power assay, respectively. Oral administration of NaAsO{sub 2} at a dose of 10 mg/kg body weight for 2 days caused significant accumulation of arsenic in cardiac tissues of the experimental mice in association with the reduction in cardiac antioxidant enzymes activities, namely superoxide dismutase, catalase, glutathione-S-transferase, glutathione reductase and glutathione peroxidase. Arsenic intoxication also decreased the cardiac glutathione (GSH) and total thiol contents and increased the levels of oxidized glutathione (GSSG), lipid peroxidation end products and protein carbonyl content. Treatment with AA at a dose of 20 mg/kg body weight for 4 days prior to NaAsO{sub 2} intoxication protected the cardiac tissue from arsenic-induced oxidative impairment. In addition to oxidative stress, arsenic administration increased total cholesterol level as well as the reduced high-density lipoprotein cholesterol level in the sera of the experimental mice. AA pretreatment, however, could prevent this hyperlipidemia. Histological studies on the ultrastructural changes in cardiac tissue supported the protective activity of AA also. Combining all, results suggest that AA could protect cardiac tissues against arsenic-induced oxidative stress probably due to its antioxidant property. (orig.)

  16. [Proliferative vitreoretinopathy: prophylactic treatment].

    Science.gov (United States)

    Chiquet, C; Rouberol, F

    2014-11-01

    Proliferative vitreoretinopathy (PVR) is a complex process. It causes contractile fibrocellular membranes that may prevent retinal reattachment. PVR therefore remains one of the most severe complications of rhegmatogenous retinal detachment (RD), with an incidence of 5-11%, and is among the most frequent causes of surgical failure (50-75%). Its severity derives from the complexity of the surgery required to treat patients and from its uncertain anatomic and functional prognosis. The first step in preventing PVR is to identify patients at risk by means of clinical and/or biological factors such as the characteristics of retinal tears (large size, number) and detachment (preexisting PVR, extent), and the use of cryotherapy. Surgeons must therefore adapt their surgical approach to the risk of PVR. The study of animal models and the natural history of the condition in humans demonstrate the importance of early antiproliferative treatment in the early stage of the disease. Combining 5-fluoro-uracil and heparin in the vitrectomy infusion lowers the rate of postoperative PVR onset in patients with PVR risk factors. The evaluation of new molecules and new dosages will lead to a decisive step in the fight against PVR. PMID:25012973

  17. Proliferative retinopathies: animal models and therapeutic opportunities.

    Science.gov (United States)

    Villacampa, Pilar; Haurigot, Virginia; Bosch, Fatima

    2015-01-01

    Proliferative retinopathies are the leading causes of blindness in Western societies. The development of new, more efficacious treatments that take advantage of recent advances in the fields of gene and cell therapy requires further investigations on the mechanisms underlying disease onset and progression, and adequate animal models that recapitulate the pathogenesis of human proliferative retinopathy and allow evaluation of the long-term therapeutic benefits that these therapies can offer. Unfortunately, most models of retinal neovascularization have short-term evolution and diabetic rodents show a very mild retinal phenotype, limited to non-proliferative changes, and do not develop proliferative retinopathy at all. Transgenic mice overexpressing Insulin-like Growth Factor-I (IGF-I) in the retina (TgIGF-I) constitute the only rodent model currently available that develops most of the retinal alterations observed in diabetic eyes, with a temporal evolution that resembles that of the human disease. TgIGF-I have retinal vascular alterations that progress as animals age from non-proliferative to proliferative disease, making these mice an excellent model of proliferative retinopathy that, due to its slow progression, allows long-term evaluation of novel antiangiogenic therapies. At the molecular level, transgenic retinas recapitulate a variety of changes that are also observed in diabetic retinas, which reinforces the validity of this model. In addition to vascular and glial alterations, Tg-IGF-I mice show progressive neurodegeneration that leads to blindness in old animals. Thus, TgIGF-I are a useful model for testing the long-term efficacy and safety of innovative antiangiogenic, glial-modulating and neuroprotective therapies for the treatment of diabetic retinopathy and other retinal proliferative disorders. PMID:25760215

  18. Grape Seed Proanthocyanidin Extract Alleviates Arsenic-induced Oxidative Reproductive Toxicity in Male Mice

    Institute of Scientific and Technical Information of China (English)

    LI Shu Gang; GUO Shu Xia; DING Yu Song; NIU Qiang; XU Shang Zhi; PANG Li Juan; MA Ru Lin; JING Ming Xia; FENG Gang Ling; LIU Jia Ming

    2015-01-01

    Objective To determine the ability of grape seed proanthocyanidin extract (GSPE) in alleviating arsenic-induced reproductive toxicity. Methods Sixty male Kunming mice received the following treatments by gavage: normal saline solution (control); arsenic trioxide (ATO; 4 mg/kg); GSPE (400 mg/kg); ATO+GSPE (100 mg/kg);ATO+GSPE (200 mg/kg) and ATO+GSPE (400 mg/kg). Thereafter, the mice were sacrificed and weighed, and the testis was examined for pathological changes. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), heme oxygenase 1 (HO1), glutathione S-transferase (GST), NAD(P)H dehydrogenase, and quinone 1 (NQO1) expression in the testis was detected by real-time PCR. Superoxide dismutase (SOD), glutathione (GSH), total antioxidative capability (T-AOC), malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), and reproductive indexes were analyzed. Results ATO-treated mice showed a significantly decreased sperm count and testis somatic index and activity levels of SOD, GSH, and T-AOC than control group. Compared to the ATO-treated group, ATO+GSPE group showed recovery of the measured parameters. Mice treated with ATO+high-dose GSPE showed the highest level of mRNA expression of Nrf2, HO, NQO1, and GST. Conclusion GSPE alleviates oxidative stress damage in mouse testis by activating Nrf2 signaling, thus counteracting arsenic-induced reproductive toxicity.

  19. A radionuclide method for evaluation of disease activity and function of the kidneys at patients with mesangial proliferative glomerulonephritis (MPGN)

    International Nuclear Information System (INIS)

    This method was made as an alternative to the renal biopsy for the evaluation of the state of the kidneys. The purpose of the study was to apply a combine radionuclide method to estimate the disease activity and function of the kidneys with MPGN proven by biopsy. 21 patients and 5 controls underwent consecutively 67Ga-citrate scintigraphy (74 MBq, 72 h p.i., firm Mallinkrodt) and immediately after that 99Tc-DTPA dynamic renal scintigraphy (185 MBq, Bulgarian Firm) without any change in body position of the patient in view to create marked 'zones of interest' of the kidneys and the background. Different qualitative parameters were determined: from 67Ga-scintigraphy-activity index (AI-uptake ratio between left kidney and soft tissue); from 99Tc-DTPA-scintigraphy-Tmax and retention index (RI-activity of the kidney cortex at 20 min p.i. to its activity at Tmax). The results obtained were compared to the biopsy finding, classified in three grades (1 - mild, 2 - moderate and 3 - severe interstitial changes). The AI ranged from 1.14 to 1.92 (average 1.64), Tmax from 3.5 to 7 min (average 5.4), RI - between 0.5 and 0.87 (average 0.71). A very good correlation between AI and biopsy (r = 0.79, p<0.05) and between RI and serum creatinine (r = 0.54, p = 0.05) was found. The comparative evaluation proves that the proposed combine radionuclide method can be useful alternative to renal biopsy for evaluation of disease activity and function of the kidneys in patients with MPGN. (author)

  20. Can synaptophysin be used as a marker of breast cancer diagnosed by core-needle biopsy in epithelial proliferative diseases of the breast?

    Science.gov (United States)

    Maeda, Ichiro; Tajima, Shinya; Ariizumi, Yasushi; Doi, Masatomo; Endo, Akira; Naruki, Saeko; Hoshikawa, Masahiro; Koizumi, Hirotaka; Kanemaki, Yoshihide; Ueno, Takahiko; Tsugawa, Koichiro; Takagi, Masayuki

    2016-07-01

    The differential diagnosis of epithelial proliferative disease using core needle biopsy (CNB) is problematic because it is difficult to differentiate between intraductal papilloma, ductal hyperplasia, ductal carcinoma in situ, and invasive ductal carcinoma. Many studies have reported that breast cancer lesions are positive for neuroendocrine (NE) markers, whereas only a small number of studies have reported immunopositivity for NE markers in normal mammary tissues or benign lesions. We asked whether NE factors could be used as markers of breast cancer. We determined the immunopositivity rate of synaptophysin, an NE marker, in 204 lesions excised from the breast using CNB in patients who visited a university-affiliated comprehensive medical facility and examined whether synaptophysin is a marker of breast cancer. The specimens were classified as synaptophysin-negative cases (56 benign, 99 malignant); equivocal cases (lesions classified as synaptophysin positive were 23.3 %, 98.2 %, 96.9 %, and 36.1 %, respectively. The respective values for lesions classified as equivocal were 11.6 %, 96.6 %, 88.2 %, and 36.1 %. Synaptophysin may provide a marker of breast cancer diagnosed by CNB. PMID:27239051

  1. [The characteristic of proliferative activity of thymocytes and peripheral blood lymphocytes in the offspring of females with experimental chronic liver diseases of various aetiology].

    Science.gov (United States)

    Briukhin, G V; Fedosov, A A

    2006-01-01

    The aim of the study was a comparative analysis of the proliferative activity of thymocytes and peripheral blood lymphocytes in the offspring of female rats with chronic liver pathology of various genesis. In adult female Wistar rats toxic and autoimmune forms of liver lesions were modeled. The offspring of these experimental animals was studied at different time points of postnatal ontogenesis. Proliferative activity of thymocytes and lymphocytes was estimated by counting the proportion of cells with multiple nucleolar organizing regions (AgNORs) and using the cytofluorometric method with acridine orange. In the offspring of experimental animals, the depression of proliferative activity of thymocytes as well as the increase of the proliferative activity of peripheral blood lymphocytes were found at all the time points studied. This was indicated by a change in a relative number of AgNORs-activated cells and a decrease of nucleic acid content in cortical thymocytes. PMID:17201321

  2. Proliferative verrucous leukoplakia: An update.

    Science.gov (United States)

    Munde, Anita; Karle, Ravindra

    2016-01-01

    Proliferative verrucous leukoplakia (PVL) is a rare form of oral leukoplakia, which was first described in 1985 by Hansen et al. Since then, various published case series have presented PVL as a disease with aggressive biological behavior due to its high probability of recurrence and a high rate of malignant transformation, usually higher than 70%. PVL is a long-term progressive condition, which is observed more frequently in elderly women, 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 with a progressive deterioration of the lesions, making it more and more difficult to control. Tobacco use does not seem to have a significant influence on the appearance or progression of PVL and may occur both in smokers and nonsmokers. Prognosis is poor for this seemingly harmless-appearing white lesion of the oral mucosa. At present, the etiology of PVL remains unclear as well as its management and diagnosis, which is still retrospective, late and poorly defined, lacking consensus criteria. This short review discusses the clinical and histopathological features, diagnosis, traditional treatment and the current management of the disease. PMID:27461595

  3. [Proliferative verrucous leukoplakia].

    Science.gov (United States)

    Lindenmüller, Irène Hitz; Lambrecht, J Thomas

    2006-01-01

    Proliferative verrucous leukoplakia (PVL) is a seldom form of oral leukoplakia (OL) with high transformation tendency. It starts as a bold hyperkeratosis changing into an exophytic verrucous form spreading in the oral cavity. The clinical diagnosis therefore is a retrospective one. PMID:16792055

  4. 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 sa...

  5. Mechanisms of HIV non-progression; robust and sustained CD4+ T-cell proliferative responses to p24 antigen correlate with control of viraemia and lack of disease progression after long-term transfusion-acquired HIV-1 infection

    Directory of Open Access Journals (Sweden)

    Geczy Andrew F

    2008-12-01

    Full Text Available Abstract Background Elite non-progressors (plasma viral load Results A survival advantage was conferred on 12 of 13 subjects, who had at least one host genetic factor (HLA, chemokine receptor or TLR polymorphisms or viral attenuating factor (defective nef associated with slow progression. However, antiviral immune responses differentiated the course of disease into and beyond the second decade of infection. A stable p24-specific proliferative response was associated with control of viraemia and retention of non-progressor status, but this p24 response was absent or declined in viraemic subjects. Strong Gag-dominant cytotoxic T lymphocyte (CTL responses were identified in most LTNP, or Pol dominant-CTL in those with nef-defective HIV infection. CTL were associated with control of viraemia when combined with p24 proliferative responses. However, CTL did not prevent late disease progression. Individuals with sustained viral suppression had CTL recognising numerous Gag epitopes, while strong but restricted responses to one or two immunodominant epitopes was effective for some time, but failed to contain viraemia over the course of this study. Viral escape mutants at a HLA B27-restricted Gag-p24 epitope were detected in only 1 of 3 individuals, whereas declining or negative p24 proliferative responses occurred in all 3 concurrent with an increase in viraemia. Conclusion Detectable viraemia at study entry was predictive of loss of LTNP status and/or disease progression in 6 of 8, and differentiated slow progressors from elite LTNP who retained potent virological control. Sustained immunological suppression of viraemia was independently associated with preserved p24 proliferative responses, regardless of the strength and breadth of the CTL response. A decline in this protective p24 response preceded or correlated with loss of non-progressor status and/or signs of disease progression.

  6. Therapeutic efficacy of silymarin and naringenin in reducing arsenic-induced hepatic damage in young rats.

    Science.gov (United States)

    Jain, Anshu; Yadav, Abhishek; Bozhkov, A I; Padalko, V I; Flora, S J S

    2011-05-01

    We investigated the effects of silymarin and naringenin in counteracting arsenic-induced hepatic oxidative stress post exposure. Male wistar rats were chronically exposed to sodium arsenite for eight months followed by oral treatment with silymarin and naringenin (50 mg/kg each) for 15 consecutive days to evaluate hepatic damage and antioxidant potential. Our results demonstrate a significant decrease in hepatic GSH levels, SOD and catalase activities and an increase in GST and TBARS levels after arsenic administration. Silymarin or naringenin administration increased GSH levels and was beneficial in the recovery of altered SOD and catalase activity besides significantly reducing blood and tissue arsenic concentration. Our results point to the antioxidant potential of these flavonoids, which might be of benefit in the clinical recovery of subject exposed to arsenic. These flavonoids can be incorporated into the diet or co-supplemented during chelation treatment, and thus may afford a protective effect against arsenite-induced cytotoxicity. PMID:20719385

  7. [Proliferative vitreoretinopathy: curative treatment].

    Science.gov (United States)

    Chiquet, C; Rouberol, F

    2014-10-01

    Proliferative vitreoretinopathy (PVR), which causes contractile fibrocellular membranes that may prevent retinal reattachment, remains one of the most severe complications of rhegmatogenous retinal detachment (RD), with an incidence of 5-11%, and one of the most frequent causes of surgical failure (50-75%). Its severity is due to the complexity of the surgery required to treat patients, and to its uncertain anatomic and functional prognosis. Curative treatment of PVR includes vitrectomy, sometimes associated with phacoemulsification or scleral buckling; systematic peeling of epiretinal membranes, occasionally retinectomy; and systematic retinopexy by endolaser photocoagulation. The current preferred internal tamponade is silicone oil. Silicone oils of various densities are undergoing comparative studies. PMID:24997865

  8. Arsenic-induced toxicity and the protective role of ascorbic acid in mouse testis

    International Nuclear Information System (INIS)

    Oxidative stress has been suggested to be a major cause of male reproductive failure. Here, we investigated whether arsenic, which impairs male reproductive functions in rodent models, acts by inducing oxidative stress. Male 8-week-old ICR mice were given drinking water containing 20 or 40 mg/l sodium arsenite with or without 0.75 or 1.5 g/l of the antioxidant ascorbic acid for 5 weeks. The arsenic-treated mice showed decreased epididymidal sperm counts and testicular weights compared to untreated mice. These effects were reversed in mice that were co-treated with ascorbic acid. Similarly, arsenic treatment lowered the activities of testicular 3β-hydroxysteroid dehydrogenase (HSD) and 17β-HSD, which play important roles in steroidogenesis, and this was reversed by co-treatment with ascorbic acid. The testicles of arsenic-treated mice had decreased glutathione (GSH) levels (which correlate inversely with the degree of cellular oxidative stress) and elevated levels of protein carbonyl (a marker of oxidative damage to tissue proteins). Ascorbic acid co-treatment reversed both of these effects. Thus, ascorbic acid blocks both the adverse effects of arsenic on male reproductive functions and the arsenic-induced testicular oxidative changes. These observations support the notion that arsenic impairs male reproductive function by inducing oxidative stress

  9. Reactive oxygen species contribute to arsenic-induced EZH2 phosphorylation in human bronchial epithelial cells and lung cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Lingzhi; Qiu, Ping; Chen, Bailing; Lu, Yongju; Wu, Kai; Thakur, Chitra; Chang, Qingshan; Sun, Jiaying; Chen, Fei, E-mail: fchen@wayne.edu

    2014-05-01

    Our previous studies suggested that arsenic is able to induce serine 21 phosphorylation of the EZH2 protein through activation of JNK, STAT3, and Akt signaling pathways in the bronchial epithelial cell line, BEAS-2B. In the present report, we further demonstrated that reactive oxygen species (ROS) were involved in the arsenic-induced protein kinase activation that leads to EZH2 phosphorylation. Several lines of evidence supported this notion. First, the pretreatment of the cells with N-acetyl-L-cysteine (NAC), a potent antioxidant, abolishes arsenic-induced EZH2 phosphorylation along with the inhibition of JNK, STAT3, and Akt. Second, H{sub 2}O{sub 2}, the most important form of ROS in the cells in response to extracellular stress signals, can induce phosphorylation of the EZH2 protein and the activation of JNK, STAT3, and Akt. By ectopic expression of the myc-tagged EZH2, we additionally identified direct interaction and phosphorylation of the EZH2 protein by Akt in response to arsenic and H{sub 2}O{sub 2}. Furthermore, both arsenic and H{sub 2}O{sub 2} were able to induce the translocation of ectopically expressed or endogenous EZH2 from nucleus to cytoplasm. In summary, the data presented in this report indicate that oxidative stress due to ROS generation plays an important role in the arsenic-induced EZH2 phosphorylation. - Highlights:: • Arsenic (As{sup 3+}) induces EZH phosphorylation. • JNK, STAT3, and Akt contribute to EZH2 phosphorylation. • Oxidative stress is involved in As{sup 3+}-induced EZH2 phosphorylation. • As{sup 3+} induces direct interaction of Akt and EZH2. • Phosphorylated EZH2 localized in cytoplasm.

  10. Reactive oxygen species contribute to arsenic-induced EZH2 phosphorylation in human bronchial epithelial cells and lung cancer cells

    International Nuclear Information System (INIS)

    Our previous studies suggested that arsenic is able to induce serine 21 phosphorylation of the EZH2 protein through activation of JNK, STAT3, and Akt signaling pathways in the bronchial epithelial cell line, BEAS-2B. In the present report, we further demonstrated that reactive oxygen species (ROS) were involved in the arsenic-induced protein kinase activation that leads to EZH2 phosphorylation. Several lines of evidence supported this notion. First, the pretreatment of the cells with N-acetyl-L-cysteine (NAC), a potent antioxidant, abolishes arsenic-induced EZH2 phosphorylation along with the inhibition of JNK, STAT3, and Akt. Second, H2O2, the most important form of ROS in the cells in response to extracellular stress signals, can induce phosphorylation of the EZH2 protein and the activation of JNK, STAT3, and Akt. By ectopic expression of the myc-tagged EZH2, we additionally identified direct interaction and phosphorylation of the EZH2 protein by Akt in response to arsenic and H2O2. Furthermore, both arsenic and H2O2 were able to induce the translocation of ectopically expressed or endogenous EZH2 from nucleus to cytoplasm. In summary, the data presented in this report indicate that oxidative stress due to ROS generation plays an important role in the arsenic-induced EZH2 phosphorylation. - Highlights:: • Arsenic (As3+) induces EZH phosphorylation. • JNK, STAT3, and Akt contribute to EZH2 phosphorylation. • Oxidative stress is involved in As3+-induced EZH2 phosphorylation. • As3+ induces direct interaction of Akt and EZH2. • Phosphorylated EZH2 localized in cytoplasm

  11. Role of reactive oxygen species in arsenic-induced transformation of human lung bronchial epithelial (BEAS-2B) cells

    International Nuclear Information System (INIS)

    Highlights: • Short term exposure of cells to arsenic causes ROS generation. • Chronical exposure of cells to arsenic causes malignant cell transformation. • Inhibition of ROS generation reduces cell transformation by arsenic. • Arsenic-transformed cells exhibit reduced capacity of generating ROS. • Arsenic-transformed cells exhibit increased levels of antioxidants. - Abstract: Arsenic is an environmental carcinogen, its mechanisms of carcinogenesis remain to be investigated. Reactive oxygen species (ROS) are considered to be important. A previous study (Carpenter et al., 2011) has measured ROS level in human lung bronchial epithelial (BEAS-2B) cells and arsenic-transformed BEAS-2B cells and found that ROS levels were higher in transformed cells than that in parent normal cells. Based on these observations, the authors concluded that cell transformation induced by arsenic is mediated by increased cellular levels of ROS. This conclusion is problematic because this study only measured the basal ROS levels in transformed and parent cells and did not investigate the role of ROS in the process of arsenic-induced cell transformation. The levels of ROS in arsenic-transformed cells represent the result and not the cause of cell transformation. Thus question concerning whether ROS are important in arsenic-induced cell transformation remains to be answered. In the present study, we used expressions of catalase (antioxidant against H2O2) and superoxide dismutase 2 (SOD2, antioxidant against O2·−) to decrease ROS level and investigated their role in the process of arsenic-induced cell transformation. Our results show that inhibition of ROS by antioxidant enzymes decreased arsenic-induced cell transformation, demonstrating that ROS are important in this process. We have also shown that in arsenic-transformed cells, ROS generation was lower and levels of antioxidants are higher than those in parent cells, in a disagreement with the previous report. The present study

  12. Role of reactive oxygen species in arsenic-induced transformation of human lung bronchial epithelial (BEAS-2B) cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Zhuo, E-mail: zhuo.zhang@uky.edu [Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536 (United States); Pratheeshkumar, Poyil; Budhraja, Amit; Son, Young-Ok [Center for Research on Environmental Diseases, University of Kentucky, Lexington, KY 40536 (United States); Kim, Donghern [Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536 (United States); Shi, Xianglin [Center for Research on Environmental Diseases, University of Kentucky, Lexington, KY 40536 (United States)

    2015-01-09

    Highlights: • Short term exposure of cells to arsenic causes ROS generation. • Chronical exposure of cells to arsenic causes malignant cell transformation. • Inhibition of ROS generation reduces cell transformation by arsenic. • Arsenic-transformed cells exhibit reduced capacity of generating ROS. • Arsenic-transformed cells exhibit increased levels of antioxidants. - Abstract: Arsenic is an environmental carcinogen, its mechanisms of carcinogenesis remain to be investigated. Reactive oxygen species (ROS) are considered to be important. A previous study (Carpenter et al., 2011) has measured ROS level in human lung bronchial epithelial (BEAS-2B) cells and arsenic-transformed BEAS-2B cells and found that ROS levels were higher in transformed cells than that in parent normal cells. Based on these observations, the authors concluded that cell transformation induced by arsenic is mediated by increased cellular levels of ROS. This conclusion is problematic because this study only measured the basal ROS levels in transformed and parent cells and did not investigate the role of ROS in the process of arsenic-induced cell transformation. The levels of ROS in arsenic-transformed cells represent the result and not the cause of cell transformation. Thus question concerning whether ROS are important in arsenic-induced cell transformation remains to be answered. In the present study, we used expressions of catalase (antioxidant against H{sub 2}O{sub 2}) and superoxide dismutase 2 (SOD2, antioxidant against O{sub 2}{sup ·−}) to decrease ROS level and investigated their role in the process of arsenic-induced cell transformation. Our results show that inhibition of ROS by antioxidant enzymes decreased arsenic-induced cell transformation, demonstrating that ROS are important in this process. We have also shown that in arsenic-transformed cells, ROS generation was lower and levels of antioxidants are higher than those in parent cells, in a disagreement with the previous

  13. Non-Proliferative Diabetic Retinopathy Vision Simulator

    Science.gov (United States)

    ... Retinopathy Vision Simulator Non-Proliferative Diabetic Retinopathy Vision Simulator Mar. 03, 2014 How does non-proliferative diabetic ... to form deposits. Previous Proliferative Diabetic Retinopathy Vision Simulator Related Ask an Ophthalmologist Answers Injection alternatives for ...

  14. EFFECTS OF ADDROGRAPHIS PANICULATA (NEES. ON ARSENIC- INDUCED ALTERED GLUCOSE HOMEOSTASIS AND OXIDATIVE IMPAIRMENT IN PANCREAS OF SWISS MICE

    Directory of Open Access Journals (Sweden)

    MANDAVA V. RAO

    2007-01-01

    Full Text Available The effect of Andrographis paniculata (Nees. on arsenic-induced changes in biochemical and cellular antioxident sytem was studies in adult female mice. Daily oral administration of arsenic trioxide (0.5 and 1.0mg/kg b.w for 30days induced a significant increase in blood glucose level which was associated with impaired glucose tolrence. Arsenic treatment also resulted in elevated level panreatic tissue specific makers such as activities of amylase and lipase in serum indicating pancreatic dysfunction. Interestingly, this biochemical dysfuntion was accompanied by a marked dose related enchancement of lipid peroxidation indicating significant induction of oxidative damage. Additional evidence such as deletion in reduced gluatathione levels and alterations in enzymic antioxidant defences like superoxide dismutase, catalase and glutathione peroxidase in pancreas suggested induction of oxidative stress. Concomitant administration of Adrographis paniculata (50 mg/kg b.w. with arsenic significant restored all these parameters. These results suggest that Adrographis paniculata is capable to reducing arsenic-induce cellular oxidative and inflammatory changes in pancreas.

  15. Inhibition of arsenic induced-rat liver injury by grape seed exact through suppression of NADPH oxidase and TGF-β/Smad activation

    International Nuclear Information System (INIS)

    Chronic arsenic exposure induces oxidative damage to liver leading to liver fibrosis. We aimed to define the effect of grape seed extract (GSE), an antioxidant dietary supplement, on arsenic-induced liver injury. First, Male Sprague-Dawley rats were exposed to a low level of arsenic in drinking water (30 ppm) with or without GSE (100 mg/kg, every other day by oral gavage) for 12 months and the effect of GSE on arsenic-induced hepatotoxicity was examined. The results from this study revealed that GSE co-treatment significantly attenuated arsenic-induced low antioxidant defense, oxidative damage, proinflammatory cytokines and fibrogenic genes. Moreover, GSE reduced arsenic-stimulated Smad2/3 phosphorylation and protein levels of NADPH oxidase subunits (Nox2, Nox4 and p47phox). Next, we explored the molecular mechanisms underlying GSE inhibition of arsenic toxicity using cultured rat hepatic stellate cells (HSCs). From the in vitro study, we found that GSE dose-dependently reduced arsenic-stimulated ROS production and NADPH oxidase activities. Both NADPH oxidases flavoprotein inhibitor DPI and Nox4 siRNA blocked arsenic-induced ROS production, whereas Nox4 overexpression suppressed the inhibitory effects of GSE on arsenic-induced ROS production and NADPH oxidase activities, as well as expression of TGF-β1, type I procollagen (Coll-I) and α-smooth muscle actin (α-SMA) mRNA. We also observed that GSE dose-dependently inhibited TGF-β1-induced transactivation of the TGF-β-induced smad response element p3TP-Lux, and that forced expression of Smad3 attenuated the inhibitory effects of GSE on TGF-β1-induced mRNA expression of Coll-I and α-SMA. Collectively, GSE could be a potential dietary therapeutic agent for arsenic-induced liver injury through suppression of NADPH oxidase and TGF-β/Smad activation. - Research Highlights: → GSE attenuated arsenic-induced low antioxidant defense, oxidative damage, proinflammatory cytokines and fibrogenic genes. → GSE reduced

  16. Chronic proliferative dermatitis in Sharpin null mice: development of an autoinflammatory disease in the absence of B and T lymphocytes and IL4/IL13 signaling.

    Directory of Open Access Journals (Sweden)

    Christopher S Potter

    Full Text Available SHARPIN is a key regulator of NFKB and integrin signaling. Mice lacking Sharpin develop a phenotype known as chronic proliferative dermatitis (CPDM, typified by progressive epidermal hyperplasia, apoptosis of keratinocytes, cutaneous and systemic eosinophilic inflammation, and hypoplasia of secondary lymphoid organs. Rag1(-/- mice, which lack mature B and T cells, were crossed with Sharpin(-/- mice to examine the role of lymphocytes in CDPM. Although inflammation in the lungs, liver, and joints was reduced in these double mutant mice, dermatitis was not reduced in the absence of functional lymphocytes, suggesting that lymphocytes are not primary drivers of the inflammation in the skin. Type 2 cytokine expression is increased in CPDM. In an attempt to reduce this aspect of the phenotype, Il4ra(-/- mice, unresponsive to both IL4 and IL13, were crossed with Sharpin(-/- mice. Double homozygous Sharpin(-/- , Il4ra(-/- mice developed an exacerbated granulocytic dermatitis, acute system inflammation, as well as hepatic necrosis and mineralization. High expression of CHI3L4, normally seen in CPDM skin, was abolished in Sharpin(-/- , Il4ra(-/- double mutant mice indicating the crucial role of IL4 and IL13 in the expression of this protein. Cutaneous eosinophilia persisted in Sharpin(-/- , Il4ra(-/- mice, although expression of Il5 mRNA was reduced and the expression of Ccl11 and Ccl24 was completely abolished. TSLP and IL33 were both increased in the skin of Sharpin(-/- mice and this was maintained in Sharpin(-/- , Il4ra(-/- mice suggesting a role for TSLP and IL33 in the eosinophilic dermatitis in SHARPIN-deficient mice. These studies indicate that cutaneous inflammation in SHARPIN-deficient mice is autoinflammatory in nature developing independently of B and T lymphocytes, while the systemic inflammation seen in CPDM has a strong lymphocyte-dependent component. Both the cutaneous and systemic inflammation is enhanced by loss of IL4 and IL13 signaling

  17. Proliferative changes in nonpalpable breast lesions detected by mammography

    International Nuclear Information System (INIS)

    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

  18. Experimental proliferative glomerulonephritis in the cat.

    Science.gov (United States)

    Bishop, S A; Stokes, C R; Lucke, V M

    1992-01-01

    A model of chronic serum sickness was used to induce immune-complex glomerulonephritis in seven experimental cats, by daily intravenous inoculation of an increasing dose (5 to 35 mg) of human serum albumin (HSA). At week four, two of the seven animals developed anterior uveitis. At week 23, two different animals developed the subcutaneous oedema characteristic of the nephrotic syndrome (NS), whilst the other five cats appeared clinically normal. The kidneys were examined at necropsy by light microscopy and by transmission electron microscopy. The glomeruli of four animals (three with both proteinuria and uraemia, and one with proteinuria only) showed morphological changes under light microscopy. The abnormalities suggested that a diffuse mesangial proliferative glomerulonephritis (GN) had been induced in three cats and diffuse membranoproliferative GN induced in another. Ultrastructural studies revealed electron-dense deposits (immune-complexes) in six of the seven cats. Two cats without glomerular abnormalities by light microscopy had mesangial deposits and three cats with mesangial proliferative GN had deposits at mesangial, subendothelial and/or subepithelial sites. The single cat with membranoproliferative GN had deposits at mesangial, subendothelial, subepithelial and intramembranous sites. Immunohistological examination (peroxidase-antiperoxidase technique) showed that HSA and immunoglobulin (IgG and IgM) were deposited in the glomeruli of these cats. Deposits were the most dense in cats with more severe renal lesions. Deposits of IgM were most abundant. An extensive cellular infiltrate, comprising macrophages, neutrophils and plasma cells, was observed only in the four animals which showed abnormalities in glomerular ultrastructure. The disease induced in these cats thus appears to differ from the membranous nephropathy previously described in the cat and bears a close resemblance to immune complex (IC) disease in man. In view of the relatively few specific

  19. Taurine prevents arsenic-induced cardiac oxidative stress and apoptotic damage: Role of NF-κB, p38 and JNK MAPK pathway

    International Nuclear Information System (INIS)

    Cardiac dysfunction is a major cause of morbidity and mortality worldwide due to its complex pathogenesis. However, little is known about the mechanism of arsenic-induced cardiac abnormalities and the use of antioxidants as the possible protective agents in this pathophysiology. Conditionally essential amino acid, taurine, accounts for 25% to 50% of the amino acid pool in myocardium and possesses antioxidant properties. The present study has, therefore, been carried out to investigate the underlying mechanism of the beneficial role of taurine in arsenic-induced cardiac oxidative damage and cell death. Arsenic reduced cardiomyocyte viability, increased reactive oxygen species (ROS) production and intracellular calcium overload, and induced apoptotic cell death by mitochondrial dependent caspase-3 activation and poly-ADP ribose polymerase (PARP) cleavage. These changes due to arsenic exposure were found to be associated with increased IKK and NF-κB (p65) phosphorylation. Pre-exposure of myocytes to an IKK inhibitor (PS-1145) prevented As-induced caspase-3 and PARP cleavage. Arsenic also markedly increased the activity of p38 and JNK MAPKs, but not ERK to that extent. Pre-treatment with SP600125 (JNK inhibitor) and SB203580 (p38 MAPK inhibitor) attenuated NF-κB and IKK phosphorylation indicating that p38 and JNK MAPKs are mainly involved in arsenic-induced NF-κB activation. Taurine treatment suppressed these apoptotic actions, suggesting that its protective role in arsenic-induced cardiomyocyte apoptosis is mediated by attenuation of p38 and JNK MAPK signaling pathways. Similarly, arsenic intoxication altered a number of biomarkers related to cardiac oxidative stress and other apoptotic indices in vivo and taurine supplementation could reduce it. Results suggest that taurine prevented arsenic-induced myocardial pathophysiology, attenuated NF-κB activation via IKK, p38 and JNK MAPK signaling pathways and could possibly provide a protection against As

  20. Reactive oxygen species mediate arsenic induced cell transformation and tumorigenesis through Wnt/β-catenin pathway in human colorectal adenocarcinoma DLD1 cells

    International Nuclear Information System (INIS)

    Long term exposure to arsenic can increase incidence of human cancers, such as skin, lung, and colon rectum. The mechanism of arsenic induced carcinogenesis is still unclear. It is generally believed that reactive oxygen species (ROS) may play an important role in this process. In the present study, we investigate the possible linkage between ROS, β-catenin and arsenic induced transformation and tumorigenesis in human colorectal adenocarcinoma cell line, DLD1 cells. Our results show that arsenic was able to activate p47phox and p67phox, two key proteins for activation of NADPH oxidase. Arsenic was also able to generate ROS in DLD1 cells. Arsenic increased β-catenin expression level and its promoter activity. ROS played a major role in arsenic-induced β-catenin activation. Treatment of DLD1 cells by arsenic enhanced both transformation and tumorigenesis of these cells. The tumor volumes of arsenic treated group were much larger than those without arsenic treatment. Addition of either superoxide dismutase (SOD) or catalase reduced arsenic induced cell transformation and tumor formation. The results indicate that ROS are involved in arsenic induced cell transformation and tumor formation possible through Wnt/β-catenin pathway in human colorectal adenocarcinoma cell line DLD1 cells. - Highlights: → Arsenic activates NADPH oxidase and increases reactive oxygen species generation in DLD1 cells. → Arsenic increases β-catenin expression. → Inhibition of ROS induced by arsenic reduce β-catenin expression. → Arsenic increases cell transformation in DLD1 cells and tumorigenesis in nude mice. → Blockage of ROS decrease cell transformation and tumorigenesis induced by arsenic.

  1. Early Onset of Atypical Proliferative Lesions in the Lungs of a Libby Amphibole (LA) Exposed Rat Model of Cardiovascular Disease-Associated Iron Overlo

    Science.gov (United States)

    Rationale: Miners and residents of Libby, Montana have increased incidences of asbestos-related diseases associated with exposure to amphibole contaminated vermiculite. Amphiboles have been shown to bind endogenous iron and modulate fiber induced inflammatory response. We hypoth...

  2. Arsenic-induced cutaneous hyperplastic lesions are associated with the dysregulation of Yap, a Hippo signaling-related protein

    Energy Technology Data Exchange (ETDEWEB)

    Li, Changzhao; Srivastava, Ritesh K.; Elmets, Craig A.; Afaq, Farrukh; Athar, Mohammad, E-mail: mathar@uab.edu

    2013-09-06

    Highlights: •Arsenic activates canonical Hippo signaling pathway and up-regulates αCatenin in the skin. •Arsenic activates transcriptional activity of Yap by its nuclear translocation. •Yap is involved in the disruption of tight/adherens junctions in arsenic-exposed animals. -- Abstract: Arsenic exposure in humans causes a number of toxic manifestations in the skin including cutaneous neoplasm. However, the mechanism of these alterations remains elusive. Here, we provide novel observations that arsenic induced Hippo signaling pathway in the murine skin. This pathway plays crucial roles in determining organ size during the embryonic development and if aberrantly activated in adults, contributes to the pathogenesis of epithelial neoplasm. Arsenic treatment enhanced phosphorylation-dependent activation of LATS1 kinase and other Hippo signaling regulatory proteins Sav1 and MOB1. Phospho-LATS kinase is known to catalyze the inactivation of a transcriptional co-activator, Yap. However, in arsenic-treated epidermis, we did not observed its inactivation. Thus, as expected, unphosphorylated-Yap was translocated to the nucleus in arsenic-treated epidermis. Yap by binding to the transcription factors TEADs induces transcription of its target genes. Consistently, an up-regulation of Yap-dependent target genes Cyr61, Gli2, Ankrd1 and Ctgf was observed in the skin of arsenic-treated mice. Phosphorylated Yap is important in regulating tight and adherens junctions through its binding to αCatenin. We found disruption of these junctions in the arsenic-treated mouse skin despite an increase in αCatenin. These data provide evidence that arsenic-induced canonical Hippo signaling pathway and Yap-mediated disruption of tight and adherens junctions are independently regulated. These effects together may contribute to the carcinogenic effects of arsenic in the skin.

  3. Arsenic-induced alterations in the contact hypersensitivity response in Balb/c mice

    International Nuclear Information System (INIS)

    Previous studies in our laboratory indicate that arsenic alters secretion of growth promoting and inflammatory cytokines in the skin that can regulate the migration and maturation of Langerhans cells (LC) during allergic contact dermatitis. Therefore, we hypothesized that arsenic may modulate hypersensitivity responses to cutaneous sensitizing agents by altering cytokine production, LC migration, and T-cell proliferation. To investigate this hypothesis, we examined the induction and elicitation phases of dermal sensitization. Mice exposed to 50 mg/l arsenic in the drinking water for 4 weeks demonstrated a reduction in lymph node cell (LNC) proliferation and ear swelling following sensitization with 2,4-dinitrofluorobenzene (DNFB), compared to control mice. LC and T-cell populations in the draining lymph nodes of DNFB-sensitized mice were evaluated by fluorescence-activated cell sorting; activated LC were reduced in cervical lymph nodes, suggesting that LC migration may be altered following arsenic exposure. Lymphocytes from arsenic-treated animals sensitized with fluorescein isothiocyanate (FITC) exhibited reduced proliferative responses following T-cell mitogen stimulation in vitro; however, lymphocyte proliferation from nonsensitized, arsenic-treated mice was comparable to controls. Arsenic exposure also reduced the number of thioglycollate-induced peritoneal macrophages and circulating neutrophils. These studies demonstrate that repeated, prolonged exposure to nontoxic concentrations of sodium arsenite alters immune cell populations and results in functional changes in immune responses, specifically attenuation of contact hypersensitivity

  4. Treatment of severe proliferative lupus nephritis: The current state

    OpenAIRE

    Mok, C; Wong, R; Lai, K.

    2003-01-01

    Despite the development of new modalities, cyclophosphamide (CYC) remains the preferred initial treatment for severe proliferative lupus nephritis. Controversies continue about the best route, dosage, and duration of CYC treatment. For recalcitrant disease, new immunosuppressive and immunomodulating agents, immunoablative high dose CYC, nucleoside analogues, apheresis, and the biological response modifiers can be considered.

  5. All-trans retinoic acid protects against arsenic-induced uterine toxicity in female Sprague-Dawley rats

    Energy Technology Data Exchange (ETDEWEB)

    Chatterjee, A.; Chatterji, U., E-mail: urmichatterji@gmail.com

    2011-12-15

    Background and purpose: Arsenic exposure frequently leads to reproductive failures by disrupting the rat uterine histology, hormonal integrity and estrogen signaling components of the rat uterus, possibly by generating reactive oxygen species. All-trans retinoic acid (ATRA) was assessed as a prospective therapeutic agent for reversing reproductive disorders. Experimental approach: Rats exposed to arsenic for 28 days were allowed to either recover naturally or were treated simultaneously with ATRA for 28 days or treatment continued up to 56 days. Hematoxylin-eosin double staining was used to evaluate changes in the uterine histology. Serum gonadotropins and estradiol were assayed by ELISA. Expression of the estrogen receptor (ER{alpha}), an estrogen responsive gene vascular endothelial growth factor (VEGF), and cell cycle regulatory proteins, cyclin D1 and CDK4, was assessed by RT-PCR, immunohistochemistry and western blot analysis. Key results: ATRA ameliorated sodium arsenite-induced decrease in circulating estradiol and gonadotropin levels in a dose- and time-dependent manner, along with recovery of luminal epithelial cells and endometrial glands. Concomitant up regulation of ER{alpha}, VEGF, cyclin D1, CDK4 and Ki-67 was also observed to be more prominent for ATRA-treated rats as compared to the rats that were allowed to recover naturally for 56 days. Conclusions and implications: Collectively, the results reveal that ATRA reverses arsenic-induced disruption of the circulating levels of gonadotropins and estradiol, and degeneration of luminal epithelial cells and endometrial glands of the rat uterus, indicating resumption of their functional status. Since structural and functional maintenance of the pubertal uterus is under the influence of estradiol, ATRA consequently up regulated the estrogen receptor and resumed cellular proliferation, possibly by an antioxidant therapeutic approach against arsenic toxicity. Highlights: Black-Right-Pointing-Pointer Arsenic

  6. Arsenic induced toxicity in broiler chicks and its alleviation with ascorbic acid: a toxico-patho-biochemical study

    Science.gov (United States)

    Khan, Ahrar; Sharaf, Rabia; Khan, Muhammad Zargham; Saleemi, Muhammad Kashif; Mahmood, Fazal

    2013-01-01

    To find out toxico-pathological effects of arsenic (As) and ameliorating effect of ascorbic acid (Vit C), broilers birds were administered 50 and 250 mg/kg arsenic and Vit C, respectively alone/in combination. As-treated birds exhibited severe signs of toxicity such as dullness, depression, increased thirst, open mouth breathing and watery diarrhea. All these signs were partially ameliorated with the treatment of Vit C. As-treated birds showed a significant decrease in serum total proteins while serum enzymes, urea and creatinine were significantly increased. Alkaline phosphatase and lactate dehydrogenase completely whereas proteins, aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea and creatinine were partial ameliorated in birds treated with As+Vit C as compared to As-treated and control birds. Pale and hemorrhagic liver and swollen kidneys were observed in As-treated birds. Histopathologically, liver exhibited congestion and cytoplasmic vacuolation while in kidneys, condensation of tubular epithelium nuclei, epithelial necrosis, increased urinary spaces, sloughing of tubules from basement membrane and cast deposition were observed in As-treated birds. Pathological lesions were partially ameliorated with the treatment of Vit C. It can be concluded that arsenic induces biochemical and histopathological alterations in broiler birds; however, these toxic effects can be partially attenuated by Vit C.

  7. Topical photodynamic therapy with 5-ALA in the treatment of arsenic-induced skin tumors

    Science.gov (United States)

    Karrer, Sigrid; Szeimies, Rolf-Markus; Landthaler, Michael

    1995-03-01

    A case of a 62-year-old woman suffering from psoriasis who was treated orally with arsenic 25 years ago is reported. The cumulative dose of arsenic trioxide was 800 mg. Since 10 years ago arsenic keratoses, basal cell carcinomas, Bowen's disease and invasive squamous cell carcinomas mainly on her hands and feet have developed, skin changes were clearly a sequence of arsenic therapy. Control of disease was poor, her right little finger had to be amputated. Topical photodynamic therapy with 5-aminolevulinic acid was performed on her right hand. Clinical and histological examinations 6 months after treatment showed an excellent cosmetic result with no signs of tumor residue.

  8. Ameliorative effect of quercetin against arsenic-induced sperm DNA damage and daily sperm production in adult male rats.

    Science.gov (United States)

    Jahan, Sarwat; Rehman, Saima; Ullah, Hizb; Munawar, Asma; Ain, Qurat Ul; Iqbal, Tariq

    2016-07-01

    In this study, the protective effect of quercetin was evaluated against arsenic induced reproductive ailments in male rats. For this purpose, male rats (n = 5/group) weighing 180-250 g were used. First group served as control, second group received arsenic (50 ppm) in drinking water. Third group was treated with quercetin (50 mg/kg) alone, while fourth group received arsenic + quercetin. All treatments were carried out for 49 days. After treatment, animals were killed by decapitation; testis and epididymis were dissected out. Right epididymis was minced immediately for comet assay, while left epididymis was processed for histology. Similarly, right testis was homogenized for estimation of daily sperm production (DSP) and detection of metal concentration. The results of our research revealed that arsenic treatment did not cause any significant change in body weight and testicular volume. Quercetin treatment significantly prevented tissue deposition of arsenic within the testis. Arsenic treatment caused a significant reduction in DSP, however, in the arsenic + quercetin-treated group and quercetin alone-treated group, DSP was significantly high as compared to the arsenic-treated group. Histological study of epididymis showed empty lumen in arsenic-treated group while in arsenic + quercetin-treated group and quercetin alone-treated group, lumen were filled with sperm and were comparable to control. Sperm DNA damage, induced by arsenic, was significantly reversed toward control levels by supplementation of quercetin. These results suggest that quercetin not only prevents deposition of arsenic in tissues, but can also protect the sperm DNA damage. PMID:26524343

  9. Long term result of intravitreal bevacizumab in a patient newly transformed to proliferative macular telangiectasia type 2

    Directory of Open Access Journals (Sweden)

    Abdullah Ozkaya

    2013-01-01

    Full Text Available The clinical and imaging findings and therapeutic outcomes of intravitreal bevacizumab injection in a patient with macular telangiectasia type 2 are described. The patient first presented with the non-proliferative stage of the disease for 4 months, then the disease transformed to the proliferative stage. In the proliferative period, the patient was treated with intravitreal bevacizumab injections as-clinically warranted. Over a follow up period lasting 26 months, the patient received 6 intravitreal bevacizumab injections, the visual acuity improved from 20/100 to 20/40, the central retinal thickness decreased from 318 microns to 198 microns. This case implies that the patients with non-proliferative macular telangiectasia type 2 should be followed carefully for proliferative transformation, and intravitreal bevacizumab treatment seems to be effective for proliferative macular telangiectasia type 2.

  10. Arsenic-induced alteration in the expression of genes related to type 2 diabetes mellitus

    International Nuclear Information System (INIS)

    Chronic exposure to high concentrations of arsenic in drinking water is associated with an increased risk for developing type 2 diabetes. The present revision focuses on the effect of arsenic on tissues that participate directly in glucose homeostasis, integrating the most important published information about the impairment of the expression of genes related to type 2 diabetes by arsenic as one of the possible mechanisms by which it leads to the disease. Many factors are involved in the manner in which arsenic contributes to the occurrence of diabetes. The reviewed studies suggest that arsenic might increase the risk for type 2 diabetes via multiple mechanisms, affecting a cluster of regulated events, which in conjunction trigger the disease. Arsenic affects insulin sensitivity in peripheral tissue by modifying the expression of genes involved in insulin resistance and shifting away cells from differentiation to the proliferation pathway. In the liver arsenic disturbs glucose production, whereas in pancreatic beta-cells arsenic decreases insulin synthesis and secretion and reduces the expression of antioxidant enzymes. The consequences of these changes in gene expression include the reduction of insulin secretion, induction of oxidative stress in the pancreas, alteration of gluconeogenesis, abnormal proliferation and differentiation pattern of muscle and adipocytes as well as peripheral insulin resistance

  11. Arsenic-induced intensity oscillations in reflection high-energy electron diffraction measurements. [during MBE of GaAs and InAs

    Science.gov (United States)

    Lewis, B. F.; Fernandez, R.; Grunthaner, F. J.; Madhukar, A.

    1986-01-01

    A technique of arsenic-induced RHEED intensity oscillations has been used to accurately measure arsenic incorporation rates as a function of substrate temperature during the homoepitaxial growths of both GaAs and InAs by molecular beam epitaxy (MBE). Measurements were made at growth temperatures from 350 to 650 C and at arsenic fluxes of 0.1 to 10.0 monolayer/s. The method measures only the arsenic actually incorporated into the growing film and does not include the arsenic lost in splitting the arsenic tetramers or lost by evaporation from the sample.

  12. 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.

  13. Inorganic Arsenic Induces NRF2-Regulated Antioxidant Defenses in Both Cerebral Cortex and Hippocampus in Vivo.

    Science.gov (United States)

    Zhang, Yang; Duan, Xiaoxu; Li, Jinlong; Zhao, Shuo; Li, Wei; Zhao, Lu; Li, Wei; Nie, Huifang; Sun, Guifang; Li, Bing

    2016-08-01

    Inorganic arsenic is reported to induce the reactive oxygen species-mediated oxidative stress, which is supposed to be one of the main mechanisms of arsenic-related neurological diseases. Nuclear factor erythroid 2-related factor 2 (NRF2), a master regulator of antioxidant defense systems, up-regulates the expression of target genes to fight against oxidative damages caused by harmful substances, including metals. In the present study, mice were used as a model to investigate the oxidative stress levels and the expressions of NRF2-regulated antioxidant substances in both cerebral cortex and hippocampus with 5, 10 and 20 mg/kg NaAsO2 exposure intra-gastrically. Our results showed that acute NaAsO2 treatment resulted in decreased total anti-oxidative capacity (T-AOC) and increased maleic dialdehyde production in the nervous system. We also detected rapidly elevation of NRF2 protein levels by enhancement of Nrf2 transcription, especially at 20 mg/kg NaAsO2 exposure group. In the meantime, mRNA and protein levels of Nrf2 encoding antioxidant enzymes heme oxygenase-1 (HO-1), NAD(P)H: quinine oxidoreductase 1 (NQO1) and glutathione S-transferase (GST) were consistently elevated time- and dose-dependently both in the cerebral cortex and hippocampus. Taken together, the presence study demonstrated the activation of NRF2 pathway, an early antioxidant defensive response, in both cerebral cortex and hippocampus upon inorganic arsenic (iAs) exposure in vivo. A better knowledge on the roles of NRF2 pathway in maintaining cellular redox homeostasis would be helpful for the strategies on improvement of neurotoxicity related to this metalloid. PMID:27165637

  14. 2,3,5,6-Tetramethylpyrazine (TMP) down-regulated arsenic-induced heme oxygenase-1 and ARS2 expression by inhibiting Nrf2, NF-κB, AP-1 and MAPK pathways in human proximal tubular cells.

    Science.gov (United States)

    Gong, Xuezhong; Ivanov, Vladimir N; Hei, Tom K

    2016-09-01

    Our recent study demonstrated that sodium arsenite at a clinically relevant dose induced nephrotoxicity in human renal proximal tubular epithelial cell line HK-2, which could be inhibited by natural product 2,3,5,6-tetramethylpyrazine (TMP) with antioxidant activity. The present study demonstrated that arsenic exposure resulted in protein and enzymatic induction of heme oxygenase-1 (HO-1) in dose- and time-dependent manners in HK-2 cells. Blocking HO-1 enzymatic activity by zinc protoporphyrin (ZnPP) augmented arsenic-induced apoptosis, ROS production and mitochondrial dysfunction, suggesting a critical role for HO-1 as a renal protectant in this procession. On the other hand, TMP, upstream of HO-1, inhibited arsenic-induced ROS production and ROS-dependent HO-1 expression. TMP also prevented mitochondria dysfunction and suppressed activation of the intrinsic apoptotic pathway in HK-2 cells. Our results revealed that the regulation of arsenic-induced HO-1 expression was performed through multiple ROS-dependent signal pathways and the corresponding transcription factors, including p38 MAPK and JNK (but not ERK), AP-1, Nrf2 and NF-κB. TMP inhibited arsenic-induced activations of JNK, p38 MAPK, ERK, AP-1 and Nrf2 and block HO-1 protein expression. The present study, furthermore, demonstrated arsenic-induced expression of arsenic response protein 2 (ARS2) that was regulated by p38 MAPK, ERK and NF-κB. To our knowledge, this is the first report showing that ARS2 involved in arsenic-induced nephrotoxicity, while TMP pretreatment prevented such an up-regulation of ARS2 in HK-2 cells. Given ARS2 and HO-1 sharing the similar regulation mechanism, we speculated that ARS2 might also mediate cell survival in this procession. In summary, our study highlighted a role of HO-1 in the protection against arsenic-induced cytotoxicity downstream from the primary targets of TMP and further indicated that TMP may be used as a potential therapeutic agent in the treatment of arsenic-induced

  15. Arsenic responsive microRNAs in vivo and their potential involvement in arsenic-induced oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Xuefeng, E-mail: xuefengr@buffalo.edu [Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York, Buffalo, NY 14214 (United States); Department of Pharmacology and Toxicology, School of Biomedical Sciences, The State University of New York, Buffalo, NY 14214 (United States); Gaile, Daniel P. [Department of Biostatistics, School of Public Health and Health Professions, the State University of New York, Buffalo, NY 14214 (United States); Gong, Zhihong [Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York, Buffalo, NY 14214 (United States); Qiu, Wenting [School of Public Health, Wenzhou Medical University, Wenzhou, Zhejiang 325035 (China); Ge, Yichen [Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York, Buffalo, NY 14214 (United States); Zhang, Chuanwu; Huang, Chenping; Yan, Hongtao [School of Public Health, Wenzhou Medical University, Wenzhou, Zhejiang 325035 (China); Olson, James R. [Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York, Buffalo, NY 14214 (United States); Department of Pharmacology and Toxicology, School of Biomedical Sciences, The State University of New York, Buffalo, NY 14214 (United States); Kavanagh, Terrance J. [Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195 (United States); Wu, Hongmei, E-mail: hongmeiwwu@hotmail.com [School of Public Health, Wenzhou Medical University, Wenzhou, Zhejiang 325035 (China)

    2015-03-15

    Arsenic exposure is postulated to modify microRNA (miRNA) expression, leading to changes of gene expression and toxicities, but studies relating the responses of miRNAs to arsenic exposure are lacking, especially with respect to in vivo studies. We utilized high-throughput sequencing technology and generated miRNA expression profiles of liver tissues from Sprague Dawley (SD) rats exposed to various concentrations of sodium arsenite (0, 0.1, 1, 10 and 100 mg/L) for 60 days. Unsupervised hierarchical clustering analysis of the miRNA expression profiles clustered the SD rats into different groups based on the arsenic exposure status, indicating a highly significant association between arsenic exposure and cluster membership (p-value of 0.0012). Multiple miRNA expressions were altered by arsenic in an exposure concentration-dependent manner. Among the identified arsenic-responsive miRNAs, several are predicted to target Nfe2l2-regulated antioxidant genes, including glutamate–cysteine ligase (GCL) catalytic subunit (GCLC) and modifier subunit (GCLM) which are involved in glutathione (GSH) synthesis. Exposure to low concentrations of arsenic increased mRNA expression for Gclc and Gclm, while high concentrations significantly reduced their expression, which were correlated to changes in hepatic GCL activity and GSH level. Moreover, our data suggested that other mechanisms, e.g., miRNAs, rather than Nfe2l2-signaling pathway, could be involved in the regulation of mRNA expression of Gclc and Gclm post-arsenic exposure in vivo. Together, our findings show that arsenic exposure disrupts the genome-wide expression of miRNAs in vivo, which could lead to the biological consequence, such as an altered balance of antioxidant defense and oxidative stress. - Highlights: • Chronic arsenic exposure induces changes of hepatic miRNA expression profiles. • Hepatic GCL activity and GSH level in rats are altered following arsenic exposure. • Arsenic induced GCL expression change is

  16. Concomitant administration of Moringa oleifera seed powder in the remediation of arsenic-induced oxidative stress in mouse.

    Science.gov (United States)

    Gupta, Richa; Dubey, D K; Kannan, G M; Flora, S J S

    2007-01-01

    Contamination of ground water by arsenic has become a cause of global public health concern. In West Bengal, India, almost 6 million people are endemically exposed to inorganic arsenic by drinking heavily contaminated groundwater through hand-pumped tube wells. No safe, effective and specific preventive or therapeutic measures for treating arsenic poisoning are available. We recently reported that some of the herbal extracts possess properties effective in reducing arsenic concentration and in restoring some of the toxic effects of arsenic in animal models. Moringa oleifera Lamarack (English: Horseradish-tree, Drumstick-tree, Hindi: Saijan, Sanskrit: Shigru) belongs to the Moringaceae family, is generally known in the developing world as a vegetable, a medicinal plant and a source of vegetable oil. The objective of the present study was to determine whether Moringa oleifera (M. oleifera) seed powder could restore arsenic induced oxidative stress and reduce body arsenic burden. Exposure to arsenic (2.5 mg/kg, intraperitoneally for 6weeks) led to a significant increase in the levels of tissue reactive oxygen species (ROS), metallothionein (MT) and thiobarbituric acid reactive substance (TBARS) which were accompanied by a decrease in the activities in the antioxidant enzymes such as superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) in mice. Arsenic exposed mice also exhibited liver injury as reflected by reduced acid phosphatase (ACP), alkaline phosphatase (ALP) and aspartate aminotransferase (AST) activities and altered heme synthesis pathway as shown by inhibited blood delta-aminolevulinic acid dehydratase (delta-ALAD) activity. Co-administration of M. oleifera seed powder (250 and 500 mg/kg, orally) with arsenic significantly increased the activities of SOD, catalase, GPx with elevation in reduced GSH level in tissues (liver, kidney and brain). These changes were accompanied by approximately 57%, 64% and 17% decrease in blood ROS, liver

  17. Arsenic responsive microRNAs in vivo and their potential involvement in arsenic-induced oxidative stress

    International Nuclear Information System (INIS)

    Arsenic exposure is postulated to modify microRNA (miRNA) expression, leading to changes of gene expression and toxicities, but studies relating the responses of miRNAs to arsenic exposure are lacking, especially with respect to in vivo studies. We utilized high-throughput sequencing technology and generated miRNA expression profiles of liver tissues from Sprague Dawley (SD) rats exposed to various concentrations of sodium arsenite (0, 0.1, 1, 10 and 100 mg/L) for 60 days. Unsupervised hierarchical clustering analysis of the miRNA expression profiles clustered the SD rats into different groups based on the arsenic exposure status, indicating a highly significant association between arsenic exposure and cluster membership (p-value of 0.0012). Multiple miRNA expressions were altered by arsenic in an exposure concentration-dependent manner. Among the identified arsenic-responsive miRNAs, several are predicted to target Nfe2l2-regulated antioxidant genes, including glutamate–cysteine ligase (GCL) catalytic subunit (GCLC) and modifier subunit (GCLM) which are involved in glutathione (GSH) synthesis. Exposure to low concentrations of arsenic increased mRNA expression for Gclc and Gclm, while high concentrations significantly reduced their expression, which were correlated to changes in hepatic GCL activity and GSH level. Moreover, our data suggested that other mechanisms, e.g., miRNAs, rather than Nfe2l2-signaling pathway, could be involved in the regulation of mRNA expression of Gclc and Gclm post-arsenic exposure in vivo. Together, our findings show that arsenic exposure disrupts the genome-wide expression of miRNAs in vivo, which could lead to the biological consequence, such as an altered balance of antioxidant defense and oxidative stress. - Highlights: • Chronic arsenic exposure induces changes of hepatic miRNA expression profiles. • Hepatic GCL activity and GSH level in rats are altered following arsenic exposure. • Arsenic induced GCL expression change is

  18. Proliferative fibrocystic lesions in association with carcinoma breast- Study of mastectomy specimens

    OpenAIRE

    R, Shashikala; Ravindra, Savithri

    2015-01-01

    Background: Breast cancer remains a global health problem with an increasing incidence. Proliferative breast diseases are recognized as one of the risk factors in the development of carcinoma. The study was undertaken to know the frequency of proliferative fibrocystic lesions in association with breast carcinomas in mastectomy specimens.Material and methods: The present study included 100 cases of mastectomies for carcinoma breast at Kempegowda Institute of Medical Sciences, Bangalore from Au...

  19. Borderline Personality Disorder: Are Proliferative Symptoms Characteristic?

    OpenAIRE

    Sansone, Randy A.; Sansone, Lori A.

    2008-01-01

    Borderline personality is an Axis II disorder that has historically encompassed a number of different psychiatric symptoms. In empirical studies, these multiple psychiatric symptoms appear to manifest as numerous comorbid Axis I and II diagnoses. In echoing these findings in primary care settings, individuals with borderline personality exhibit prolific somatic symptoms. Rather than the type of symptom, are the number of symptoms suggestive of this disorder, such that proliferative psychiatri...

  20. Proliferative capacity of murine hematopoietic stem cells

    International Nuclear Information System (INIS)

    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

  1. Poly(lactic-co-glycolic) acid loaded nano-insulin has greater potentials of combating arsenic induced hyperglycemia in mice: Some novel findings

    Energy Technology Data Exchange (ETDEWEB)

    Samadder, Asmita; Das, Jayeeta; Das, Sreemanti; De, Arnab; Saha, Santu Kumar; Bhattacharyya, Soumya Sundar; Khuda-Bukhsh, Anisur Rahman, E-mail: prof_arkb@yahoo.co.in

    2013-02-15

    Diabetes is a menacing problem, particularly to inhabitants of groundwater arsenic contaminated areas needing new medical approaches. This study examines if PLGA loaded nano-insulin (NIn), administered either intraperitoneally (i.p.) or through oral route, has a greater cost-effective anti-hyperglycemic potential than that of insulin in chronically arsenite-fed hyperglycemic mice. The particle size, morphology and zeta potential of nano-insulin were determined using dynamic light scattering method, scanning electronic and atomic force microscopies. The ability of the nano-insulin (NIn) to cross the blood–brain barrier (BBB) was also checked. Circular dichroic spectroscopic (CD) data of insulin and nano-insulin in presence or absence of arsenic were compared. Several diabetic markers in different groups of experimental and control mice were assessed. The mitochondrial functioning through indices like cytochrome c, pyruvate-kinase, glucokinase, ATP/ADP ratio, mitochondrial membrane potential, cell membrane potential and calcium-ion level was also evaluated. Expressions of the relevant marker proteins and mRNAs like insulin, GLUT2, GLUT4, IRS1, IRS2, UCP2, PI3, PPARγ, CYP1A1, Bcl2, caspase3 and p38 for tracking-down the signaling cascade were also analyzed. Results revealed that i.p.-injected nano-encapsulated-insulin showed better results; NIn, due to its smaller size, faster mobility, site-specific release, could cross BBB and showed positive modulation in mitochondrial signaling cascades and other downstream signaling molecules in reducing arsenic-induced-hyperglycemia. CD data indicated that nano-insulin had less distorted secondary structure as compared with that of insulin in presence of arsenic. Thus, overall analyses revealed that PLGA nano-insulin showed better efficacy in combating arsenite-induced-hyperglycemia than that of insulin and therefore, has greater potentials for use in nano-encapsulated form. - Highlights: ► PLGA encapsulated nano

  2. CRYPTOSPORIDIOSIS ASSOCIATED WITH EMACIATION AND PROLIFERATIVE GASTRITIS IN A LABORATORY SOUTH AFRICAN CLAWED FROG

    Science.gov (United States)

    A 2-year-old emaciated female South African Clawed frog (Xenopus laevis) was euthanized due to chronic weight loss. At postmortem, there was no evidence of bacterial, fungal or viral disease, however, the histological findings indicated a proliferative gastritis and the presence of numerous Cryptosp...

  3. Protective Effects of Combined Selenium and Punica granatum Treatment on Some Inflammatory and Oxidative Stress Markers in Arsenic-Induced Hepatotoxicity in Rats.

    Science.gov (United States)

    Shafik, Noha M; El Batsh, Maha M

    2016-01-01

    Oxidative stress is one of the major mechanisms implicated in inorganic arsenic poisoning. Punica granatum is known by its free radical scavenging properties. The aim of this study was to evaluate the protective role of combined selenium and P. granatum against arsenic-induced liver injury. Seventy-five female albino rats were divided into five groups (of 15 rats each). Toxicity was induced by oral sodium arsenite (5.5 mg/kg body weight (bw) daily) (group ІІ). Treatment of arsenic-intoxicated rats was induced by daily oral administration of sodium selenite (3 mg/kg bw) (group ІІІ), 100 mg of P. granatum ethanol extract per kilogram body weight dissolved in 300 mL distilled water in three divided doses (100 mL of this suspension every 8 h) (group IV), and combined daily oral treatment with both selenite and P. granatum ethanol extract (group V). After 3 weeks, serum and liver tissues were obtained from the decapitated rats for different estimations. Hepatotoxicity was demonstrated by significant elevation in liver weights and activities of liver enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and decrease in serum total proteins and albumin (p granatum and selenium. It was concluded that combined P. granatum and selenium treatment had a synergistic hepatoprotective effect against arsenic toxicity through activation of Nrf2 anti-oxidant pathway. PMID:26085057

  4. Molecular characterization of Oryza sativa arsenic-induced RING E3 ligase 1 (OsAIR1): Expression patterns, localization, functional interaction, and heterogeneous overexpression.

    Science.gov (United States)

    Hwang, Sun-Goo; Park, Hyeon Mi; Han, A-Reum; Jang, Cheol Seong

    2016-02-01

    High levels of arsenic (As) in plants are a serious threat to human health, and arsenic accumulation affects plant metabolism and ultimately photosynthesis, growth, and development. We attempted to isolate As-responsive Really Interesting New Gene (RING) E3 ubiquitin ligase genes from rice, and we have designated one such gene Oryza sativa arsenic-induced RING E3 ligase 1 (OsAIR1). OsAIR1 expression was induced under abiotic stress conditions, including drought, salt, heat, and As exposure. Results from an in vitro ubiquitination assay showed that OsAIR1 possesses E3 ligase activity. Within the cell, the expression of this gene was found to be localized to the vacuole. In a network-based analysis, we found significantly enriched gene ontology (GO) functions, which included ribonucleoprotein complexes such as ribosomes, suggesting that the function of OsAIR1 are related to translation. Differences in the proportion of seedlings with expanded cotyledons and root lengths, and the lack of differences in germination rates between OsAIR1-overexpressing lines and control plants under AsV stress, suggest that OsAIR1 may positively regulate post-germination plant growth under stress conditions. PMID:26788958

  5. Differential expression of follistatin and FLRG in human breast proliferative disorders

    International Nuclear Information System (INIS)

    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. 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. 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. 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 present findings indicate that an increased FST and FLRG

  6. Proliferative activity (ki-67 expression) and outcome in high grade osteosarcoma: a study of 27 cases.

    Science.gov (United States)

    Jong, R; Davis, A M; Mendes, M G; Wunder, J S; Bell, R S; Kandel, R

    2000-01-01

    Purpose. Although pre-operative chemotherapy has improved the prognosis for individuals with osteosarcoma, approximately 40% of patients will die of their disease.The aim of this study was to quantitate proliferative activity in high grade osteosarcomas and to determine whether proliferation is a prognostic factor.Patients. The study consisted of 27 patients with high grade non-metastatic osteosarcoma at various sites for whom pre-operative biopsies and resection specimens were available for review. All patients were treated similarly and had at least 24 months' follow-up from the date of diagnosis.Methods. Proliferative activity (Ki-67 expression) was examined in the diagnostic biopsies immunohistochemically using the MIB-1 antibody. Proliferation was quantitated in two ways; (1) the number of immunopositive cells was counted manually using an ocular grid; or (2) the percentage of immunopositive nuclear area was assessed using morphometric image analysis. Proliferative index was evaluated in relation to patient outcome.Results. Proliferative activity was seen in all biopsies.The median proliferative index as determined by counting cells was 24% (mean of 27%, range of 7-61%) and by image analysis was 2% (mean 3%, range 0.32-8.4).The correlation between MIB-1 proliferation indices determined either by image analysis methodology or manual cell counting was high (Spearman's rho=0.79). Proliferative index did not appear to predict either disease-free or overall survival.Discussion. Tumor proliferation does not appear to be prognostic for high grade osteosarcomas.Whether assessment of this feature in conjunction with other tumor characteristics might be prognostic requires further study. PMID:18521434

  7. Proliferative glomerulonephritis and primary antiphospholipid syndrome

    International Nuclear Information System (INIS)

    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)

  8. Lawsonia intracellularis proliferative enteropathy in a foal.

    Science.gov (United States)

    Feary, D J; Gebhart, C J; Pusterla, N

    2007-03-01

    A weanling foal was diagnosed with proliferative enteropathy caused by Lawsonia intracellularis based on history, clinical findings of depression, anorexia, weight loss, colic, diarrhea, and ventral edema, and a combination of serology and fecal PCR. An epidemiological investigation on the premises revealed that many of the other foals and adult horses were seropositive for L. intracellularis, despite being clinically normal, and identified a dog as a potential carrier and source of infection for the foal. The foal was successfully treated with a combination of azithromycin and rifampin. PMID:17410971

  9. Intraductal Proliferative Lesions of the Breast—Terminology and Biology Matter: Premalignant Lesions or Preinvasive Cancer?

    OpenAIRE

    Maria Mauri; Lucio Fortunato; Leopoldo Costarelli; Domenico Campagna

    2012-01-01

    Morphological criteria for the diagnosis of intraductal proliferative lesions of the breast have been an object of research and much controversy, and its terminology is rather confusing. Knowledge of the molecular aspects of this disease probably necessitates further research to clarify if these entities can be identified as breast cancer precursors or as a malignant preinvasive disease. These issues are of great interest not only for their biological implications, but also to the clinician w...

  10. Benign Proliferative Breast Lesions and Risk of Cancer

    OpenAIRE

    Serap Erel

    2010-01-01

    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 incre...

  11. 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

  12. [Proliferative vitreoretinopathy: pathophysiology and clinical diagnosis].

    Science.gov (United States)

    Rouberol, F; Chiquet, C

    2014-09-01

    Proliferative vitreoretinopathy (PVR) remains one of the most common causes of failed retinal detachment (RD) surgery. Many histological and clinical studies have highlighted the chain of events leading to PVR: cellular migration into the vitreous cavity, cellular differentiation, myofibroblast proliferation and activation, synthesis of extracellular matrix proteins, then contraction of preretinal tissues. The development of PVR can be explained schematically by cellular exposure to growth factors and cytokines (particularly retinal pigment epithelial cells and glial cells), in the context of break-down of the blood-retinal barrier (inflammation, choroidal detachment, iatrogenic effect of cryotherapy and surgery) and of cellular contact with the vitreous. Although the pathophysiology of PVR is now better understood, its severity remains an issue. A systematic search for preoperative PVR risk factors allows the most suitable therapeutic option to be chosen. PMID:24997864

  13. Homocysteine Serum Levels in Diabetic Patients with Non Proliferative, Proliferative and without Retinopathy

    Directory of Open Access Journals (Sweden)

    Giulia Malaguarnera

    2014-01-01

    Full Text Available Homocysteine has been associated with extracellular matrix changes. The diabetic retinopathy is a neurovascular complication of diabetes mellitus and it is the leading cause of vision loss among working adults worldwide. In this study, we evaluate the role of homocysteine in diabetic retinopathy analyzing the plasma levels of homocysteine in 63 diabetic type 2 patients with nonproliferative retinopathy (NPDR, 62 patients with proliferative diabetic retinopathy (PDR, 50 healthy subjects used as control group, and 75 randomly selected patients.

  14. 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).

  15. Antimicrobial susceptibility of ileal symbiont intracellularis isolated from pigs with proliferative enteropathy.

    OpenAIRE

    McOrist, S.; Mackie, R A; Lawson, G H

    1995-01-01

    Proliferative enteropathy is caused by the microaerophilic obligate intracellular bacterium ileal symbiont (IS) intracellularis. Treatment of this disease is problematic because of the lack of in vivo or in vitro data on the activities of antimicrobial agents. A new procedure for determining the susceptibility of IS intracellularis was developed by using a tissue culture system which promotes the in vitro multiplication of this organism. Nineteen antimicrobial agents were evaluated in triplic...

  16. A rare case of transition to membranous lupus nephritis from diffuse proliferative lupus nephritis

    OpenAIRE

    Nishi, Hitomi; Sugimoto, Keisuke; FUJITA, Shinsuke; Miyazawa, Tomoki; Enya, Takuji; Izu, Akane; Wada, Norihisa; Okada, Mitsuru; Takemura, Tsukasa

    2014-01-01

    [Abstract] Lupus nephritis is an important complication of systemic lupus erythematosus (SLE) that affects the prognosis. A rare type of lupus nephritis, class V, shows histological findings resembling those of membranous nephropathy. While most diffuse proliferative lupus nephritis is associated with other SLE disease activity, class V lupus nephritis can occur without systemic activity. Furthermore, Class V is less responsive to steroid therapy than other forms of lupus nephritis. We treate...

  17. Leptin: A proliferative factor for breast cancer?

    International Nuclear Information System (INIS)

    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

  18. Analysis on Pathogenesis of 50 Cases of Bladder Proliferative Lesions

    Institute of Scientific and Technical Information of China (English)

    陈志强; 蓝儒竹; 叶章群; 杨为民

    2003-01-01

    In order to study the pathogenesis, clinical and pathological characteristics of prolifera-tive lesions of the bladder, 50 cases of proliferative lesions of the bladder from 150 patients withcomplaints of frequency, urgency, hematuria and dysuria were subjected to cystoscopic biopsy ofthe suspicious foci in the bladder. In combination with the symptoms, urine routine and urodynam-ics, the relationship of proliferative lesions of the bladder to the inflammation and obstruction of thelower urinary tract was analyzed. Of the 50 cases of proliferative bladder lesions, 44 cases (88%)had lower urinary tract infection and 29 (58%) lower urinary tract obstruction. The patients withlower urinary tract obstruction were all complicated with infection. Three cases were associatedwith transitional cell carcinoma. Malignant cells were detected in 1 case by urinary cytologic exami-nation. Proliferative lesions of the bladder, especially those without other obvious mucosa changesunder cystoscopy, are common histological variants of urothelium in the patients with chronic in-flammation and obstruction of the lower urinary tract. Chronic inflammation and obstruction of thelower urinary tract might be the causes for proliferative lesions of the bladder. It is suggested thatdifferent treatments should be applied according to the scope and histological type of the prolifera-tive lesions.

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. Severe proliferative congenital temporomandibular joint ankylosis: a proposed treatment protocol utilizing distraction osteogenesis.

    Science.gov (United States)

    Bartlett, Scott P; Reid, Russell R; Losee, Joseph E; Quinn, Peter D

    2006-05-01

    The classical treatment for temporomandibular joint (TMJ) ankylosis in children: 1) joint release; 2) arthroplasty; 3) reconstruction; and 4) postoperative physical therapy (PT), is often unsuccessful. Postoperative physical therapy is difficult in the young patient due to poor cooperation. Moreover, there is a subgroup of patients who have a refractory congenital proliferative bony process that is the cause of their disease. In these patients, a role for distraction osteogenesis (DO) has been defined. We present a series of young patients with congenital proliferative TMJ ankylosis. Some have failed classic treatment. In such cases, DO is used to expand the mandibular size and soft tissue matrix. This creates a static open bite, facilitates mid-facial growth, and avoids compromise of the airway, speech, nutrition, and oral hygiene. To maintain these objectives, mandibular DO may be repeated as the child matures. Once skeletal maturity is reached, DO is used to normalize occlusion and further expand the soft tissue envelope prior to definitive reconstruction and aggressive post-op PT. In seven patients, this protocol has been used. Five patients are currently in the active phase of growth and undergoing interim treatment with mandibular DO. Two patients have reached skeletal maturity and have completed the protocol of DO with definitive arthroplasty and reconstruction. DO is a valuable aid in the treatment of the problematic child with congenital proliferative TMJ ankylosis. Interim DO, prior to definitive arthroplasty and reconstruction, can provide a static open bite that prevents progressive deformity and its associated functional disturbances. PMID:16770209

  5. Activation of NADPH-recycling systems in leaves and roots of Arabidopsis thaliana under arsenic-induced stress conditions is accelerated by knock-out of Nudix hydrolase 19 (AtNUDX19) gene.

    Science.gov (United States)

    Corpas, Francisco J; Aguayo-Trinidad, Simeón; Ogawa, Takahisa; Yoshimura, Kazuya; Shigeoka, Shigeru

    2016-03-15

    NADPH is an important cofactor in cell growth, proliferation and detoxification. Arabidopsis thaliana Nudix hydrolase 19 (AtNUDX19) belongs to a family of proteins defined by the conserved amino-acid sequence GX5-EX7REUXEEXGU which has the capacity to hydrolyze NADPH as a physiological substrate in vivo. Given the importance of NADPH in the cellular redox homeostasis of plants, the present study compares the responses of the main NADPH-recycling systems including NADP-isocitrate dehydrogenase (ICDH), glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH) and NADP-malic enzyme (ME) in the leaves and roots of Arabidopsis wild-type (Wt) and knock-out (KO) AtNUDX19 mutant (Atnudx19) plants under physiological and arsenic-induced stress conditions. Two major features were observed in the behavior of the main NADPH-recycling systems: (i) under optimal conditions in both organs, the levels of these activities were higher in nudx19 mutants than in Wt plants; and, (ii) under 500μM AsV conditions, these activities increase, especially in nudx19 mutant plants. Moreover, G6PDH activity in roots was the most affected enzyme in both Wt and nudx19 mutant plants, with a 4.6-fold and 5.0-fold increase, respectively. In summary, the data reveals a connection between the absence of chloroplastic AtNUDX19 and the rise in all NADP-dehydrogenase activities under physiological and arsenic-induced stress conditions, particularly in roots. This suggests that AtNUDX19 could be a key factor in modulating the NADPH pool in plants and consequently in redox homeostasis. PMID:26878367

  6. 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.

  7. Proliferative Trichilemmal Tumor in the Axillary Site: Case Report

    Directory of Open Access Journals (Sweden)

    Evren Fidan

    2011-03-01

    Full Text Available Proliferative trichilemmal tumor is a skin neoplasm derived from a hair follicle. It is more frequent in women and its prevalance increases after the 6th decade. Although the most frequent site is mentioned as hairy skin, it can also be detected on the neck, face, ear, hand and vulva. In this case, we discussed a 49 year old female patient presenting with a mass at right axillary region. The result of biopsy demonstrated that it was a proliferative trichilemmal tumor. The patient was re-operated due to the presence of surgical border positivity. The patient, who had no adjuvant treatment, is under follow-up and in remission.

  8. Reactivity in ELISA with DNA-loaded nucleosomes in patients with proliferative lupus nephritis.

    Science.gov (United States)

    Dieker, Jürgen; Schlumberger, Wolfgang; McHugh, Neil; Hamann, Philip; van der Vlag, Johan; Berden, Jo H

    2015-11-01

    Autoantibodies against nucleosomes are considered a hallmark of systemic lupus erythematosus (SLE). We compared in patients with proliferative lupus nephritis the diagnostic usefulness of a dsDNA-loaded nucleosome ELISA (anti-dsDNA-NcX) with ELISAs in which dsDNA or nucleosomes alone were coated. First, we analysed whether DNA loading on nucleosomes led to masking of epitopes by using defined monoclonal anti-DNA, anti-histone and nucleosome-specific autoantibodies to evaluate the accessibility of nucleosomal epitopes in the anti-dsDNA-NcX ELISA. Second, autoantibody levels were measured in these 3 ELISAs in 100 patients with proliferative lupus nephritis (LN) before immunosuppressive treatment and in 128 non-SLE disease controls. In patients with LN inter-assay comparisons and associations with clinical and serological parameters were analysed. The panel of monoclonal antibodies revealed that all epitopes were equally accessible in the anti-dsDNA-NcX ELISA as in the two other ELISAs. Patients with proliferative lupus nephritis were positive with dsDNA-loaded nucleosomes in 86%, with DNA in 66% and with nucleosomes in 85%. In the non-lupus disease control group these frequencies were 1.6% (2 out of 128) for both the anti-dsDNA-NcX and the anti-dsDNA ELISA and 0% in the anti-nucleosome ELISA. The levels in the anti-dsDNA-NcX ELISA were high in a group of patients with LN that showed absent reactivity in the anti-DNA or low levels in the anti-nucleosome ELISA. Anti-dsDNA-NcX positivity was associated with higher SLEDAI scores within this group. Within nucleosome-based ELISAs, we propose the anti-dsDNA-NcX ELISA as the preferred test system. PMID:26597199

  9. Dutch guidelines for diagnosis and therapy of proliferative lupus nephritis.

    NARCIS (Netherlands)

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

    2012-01-01

    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 fa

  10. 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.

    2012-01-01

    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 fa

  11. Mechanisms of immunosuppression by organotins : apoptosis vs. proliferative arrest

    NARCIS (Netherlands)

    Gennari, Alessandra

    2001-01-01

    Mechanisms of immunosuppression by organotins-apoptosis vs. proliferative arrest. The organotin compounds di-n-butyltin dichloride (DBTC) and trin-butyltin chloride (TBTC), used as stabilizers and biocides respectively, induce thymus atrophy inhibiting immature thymocyte proliferation. The aim of

  12. Imaging findings in children with proliferative disorders following multivisceral transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Hryhorczuk, Anastasia L. [Tufts Medical Center, Department of Radiology, Boston, MA (United States); Kim, Heung Bae [Boston Children' s Hospital, Department of Surgery, Boston, MA (United States); Harris, Marian H.; Vargas, Sara O. [Boston Children' s Hospital, Department of Pathology, Boston, MA (United States); Zurakowski, David [Boston Children' s Hospital, Department of Biostatistics, Boston, MA (United States); Lee, Edward Y. [Boston Children' s Hospital and Harvard Medical School, Departments of Radiology and Medicine, Boston, MA (United States)

    2015-08-15

    Multivisceral transplantation represents an important treatment option for children with intestinal failure. The attendant immunosuppression can lead to a spectrum of cellular proliferations including benign and malignant smooth muscle tumors and lymphoproliferative disorders, many related to cellular dysregulation from Epstein-Barr virus infection. The purpose of this study is to investigate the rates of post-transplantation proliferative disorders among children with multivisceral transplantation and to characterize the imaging and pathological features of these disorders. We identified all consecutive children who underwent multivisceral transplant from August 2004 to October 2011 with at least 27 months of clinical and imaging follow-up. We reviewed medical records to determine the underlying causes of the multivisceral transplant, age at transplantation, onset of neoplasm development, and outcome. Two pediatric radiologists reviewed all imaging studies independently and diagnosis of disease was made by consensus interpretation. Pathological specimens were reviewed for histopathological findings of post-transplantation neoplasm in this pediatric patient population. The study population consisted of 14 consecutive pediatric patients (7 boys and 7 girls; mean age 26 months, range 4-113 months). Of these 14 children, 4 (29%) developed histologically confirmed post-transplant neoplasms at a mean time of 2.4 years after multivisceral transplantation. Types of neoplasms included post-transplant lymphoproliferative disorder (PTLD) in three (21%) and Epstein-Barr-virus-associated smooth muscle tumor in two (14%). (One child developed both neoplasms following transplantation). Both children with smooth muscle tumor associated with Epstein-Barr virus presented with characteristic hypointense solid masses with peripheral rim enhancement on cross-sectional imaging studies. The mortality rate of children who developed post-transplant neoplasms was higher than that of those

  13. Imaging findings in children with proliferative disorders following multivisceral transplantation

    International Nuclear Information System (INIS)

    Multivisceral transplantation represents an important treatment option for children with intestinal failure. The attendant immunosuppression can lead to a spectrum of cellular proliferations including benign and malignant smooth muscle tumors and lymphoproliferative disorders, many related to cellular dysregulation from Epstein-Barr virus infection. The purpose of this study is to investigate the rates of post-transplantation proliferative disorders among children with multivisceral transplantation and to characterize the imaging and pathological features of these disorders. We identified all consecutive children who underwent multivisceral transplant from August 2004 to October 2011 with at least 27 months of clinical and imaging follow-up. We reviewed medical records to determine the underlying causes of the multivisceral transplant, age at transplantation, onset of neoplasm development, and outcome. Two pediatric radiologists reviewed all imaging studies independently and diagnosis of disease was made by consensus interpretation. Pathological specimens were reviewed for histopathological findings of post-transplantation neoplasm in this pediatric patient population. The study population consisted of 14 consecutive pediatric patients (7 boys and 7 girls; mean age 26 months, range 4-113 months). Of these 14 children, 4 (29%) developed histologically confirmed post-transplant neoplasms at a mean time of 2.4 years after multivisceral transplantation. Types of neoplasms included post-transplant lymphoproliferative disorder (PTLD) in three (21%) and Epstein-Barr-virus-associated smooth muscle tumor in two (14%). (One child developed both neoplasms following transplantation). Both children with smooth muscle tumor associated with Epstein-Barr virus presented with characteristic hypointense solid masses with peripheral rim enhancement on cross-sectional imaging studies. The mortality rate of children who developed post-transplant neoplasms was higher than that of those

  14. 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.

  15. 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

  16. Proliferative periostitis of the mandibular ramus and condyle: a case report.

    Science.gov (United States)

    Seok, Hyun; Kim, Seong-Gon; Song, Ji-Young

    2015-08-01

    Proliferative periostitis is a rare form of osteomyelitis that is characterized by new bone formation with periosteal reaction common causes of proliferative periostitis are dental caries, periodontitis, cysts, and trauma. While proliferative periostitis typically presents as a localized lesion, in this study, we describe an extensive form of proliferative periostitis involving the whole mandibular ramus and condyle. Because the radiographic findings were similar to osteogenic sarcoma, an accurate differential diagnosis was important for proper treatment. PMID:26339579

  17. Proliferative periostitis of the mandibular ramus and condyle: a case report

    OpenAIRE

    Seok, Hyun; Kim, Seong-Gon; Song, Ji-Young

    2015-01-01

    Proliferative periostitis is a rare form of osteomyelitis that is characterized by new bone formation with periosteal reaction common causes of proliferative periostitis are dental caries, periodontitis, cysts, and trauma. While proliferative periostitis typically presents as a localized lesion, in this study, we describe an extensive form of proliferative periostitis involving the whole mandibular ramus and condyle. Because the radiographic findings were similar to osteogenic sarcoma, an acc...

  18. 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

    was 42.9% among patients at risk. In a multivariate analysis, baseline HbA(1) (OR 2.14 per 1% increase, 95% CI 1.06-4.31) and non-proliferative retinopathy (OR 4.61, 95% CI 1.94-11.0) were the only risk factors for incident proliferative retinopathy. The long-term incidence of proliferative...

  19. Heparins for proliferative nephritides? Short review on an advancing topic.

    Science.gov (United States)

    Wardle, E N

    1996-01-01

    The rationale behind a proposed use of heparins for the control of proliferative nephritides is presented. Heparins stop adhesion of leucocytes to endothelial cells, they are anti-complementary, they modulate the activities of phagocytes and they stop the proliferation of mesangial cells or vascular smooth muscle cells. Heparins prevent the release of endothelin-1 and potentiate the action of constitutive nitric oxide. Low-molecular-weight heparins or pentosan polysulphate are now favoured. PMID:8856244

  20. Platelet and coagulation factors in proliferative diabetic retinopathy.

    OpenAIRE

    Borsey, D. Q.; Prowse, C. V.; Gray, R S; Dawes, J.; James, K.; Elton, R A; Clarke, B F

    1984-01-01

    Plasma beta-thromboglobulin, platelet factor 4, fibrinogen, fibrinopeptide A, antithrombin III, factor VIII related antigen, alpha 2-macroglobulin, platelet count, and total glycosylated haemoglobin were measured in three well matched groups of subjects: non-diabetic controls, diabetics without retinopathy, and diabetics with proliferative retinopathy. beta-thromboglobulin and platelet factor 4 concentrations were significantly higher in the diabetics with retinopathy than in the controls and...

  1. The pathophysiology of proliferative vitreoretinopathy in its management.

    Science.gov (United States)

    Ryan, S J

    1985-07-15

    Cellular proliferation following retinal reattachment surgery frequently results in contraction and subsequent recurrent detachment of the retina, negating an initial successful reattachment. This process has been called by a variety of names, such as massive vitreous retraction, massive preretinal retraction, and, more recently, proliferative vitreoretinopathy. Although a good start has been made by the Retina Society to classify the various types of proliferative vitreoretinopathy, some modifications in the classification are required. The fundamental problem in the treatment of proliferative vitreoretinopathy is a lack of knowledge regarding the factors that stimulate the proliferation of cells. The vitreoretinal surgeon should recognize in the life cycle of this process that stage which an eye with retinal detachment has reached. If there is no active cellular proliferation, then a scleral buckle will usually suffice. If there is traction from epiretinal membranes which cannot be relieved by a buckle, then vitrectomy and adjunct procedures are necessary. If there is active cellular proliferation and epiretinal membranes, then the arguments related to proper timing of vitrectomy must be considered. In cases where the retinal holes can be identified and closed, scleral buckling may be performed with subsequent delayed vitrectomy. In most cases, in my experience, a combination of revision of the scleral buckle is required at the time of vitrectomy and membrane segmentation for proliferative vitreoretinopathy. Until such time as drugs are available to inhibit cellular proliferation or until our basic understanding of the cell biology of this process allows other means of pharmacologic intervention, mechanical approaches will remain necessary for the treatment of the most advanced cases. PMID:4014372

  2. Intense Pulsed-Light Therapy for Proliferative Haemangiomas of Infancy

    OpenAIRE

    Marie Caucanas; Philippe Paquet; Frédérique Henry; Claudine Piérard-Franchimont; Marie-Annick Reginster; Gérald E. Piérard

    2011-01-01

    Infantile haemangioma therapy has long been a wait-and-see policy. Since recent development of laser and light therapy, pulsed dye laser has been successfully used for treating superficial haemangiomas. Few studies have been published about treatment with intense pulsed light (IPL) to assess the risk/benefit of IPL in the treatment of infantile haemangiomas during their early proliferative phase. In the present retrospective cohort study, we retrieved data about a series of 14 Caucasian child...

  3. PROLIFERATIVE INFLAMMATORY ATROPHY: POTENTIAL PRECURSOR LESION FOR PROSTATIC ADENOCARCINOMA

    Directory of Open Access Journals (Sweden)

    Benedetti-Padrón Inés

    2014-01-01

    Full Text Available Introduction: Prostatic Intraepithelial neoplasia (PIN is currently considered as the only precursor lesion of prostate cancer (PCa; nevertheless, some years ago, it has been suspected that the atrophic lesions also might be involved in its carcinogenesis. In 1999, De Marzo prospered, the expression Proliferative Inflammatory Atrophy (PIA to denominate a lesion located in the peripheral area of the gland, with epithelial cells with high proliferative potential, frequently accompanied of inflammation that has been postulated as possible precursor lesion of PIN and PCa. Objective: To review the concepts about Proliferative Inflammatory Atrophy (PIA, its morphological, genetics and molecular characteristics and to explain the precursor capacity of PIN and PCa. Methods: Databases Pubmed, Sciencedirect, EBSCOhost and OvidSP were reviewed in search of studies, systematic reviews, consensus and meta-analyses with keywords: Proliferative Inflammatory Atrophy, Prostatic Atrophy, Prostatic Carcinoma, using as due date December of 2012. Results: Molecular disorders described in PIA support the beginning of these lesions in a context of oxidative stress, possibly caused by the surrounding inflammatory cells, which induce the expression of defense gene against the oxidative damage of the genome in some epithelial cells, while those that fail in the expression of these gene become vulnerable to oxidants and electrophiles, which do them prone to develop genetic disorders that will benefit their transformation in cells of PIN and PCa. The morphological association PIA-PIN/PCa points to a progressive relationship between these lesions.Conclusion: Topographic association and morphological transition of PIA with PIN and PCa have been observed. Besides, genetic, somatic and molecular disorders have been reported in PIA, similar to those observed in PIN and PCa due to it has been postulated as possible precursor lesion of both. Nevertheless, this approach is

  4. Th1 and Th17 cells induce proliferative glomerulonephritis.

    Science.gov (United States)

    Summers, Shaun A; Steinmetz, Oliver M; Li, Ming; Kausman, Joshua Y; Semple, Timothy; Edgtton, Kristy L; Borza, Dorin-Bogdan; Braley, Hal; Holdsworth, Stephen R; Kitching, A Richard

    2009-12-01

    Th1 effector CD4+ cells contribute to the pathogenesis of proliferative and crescentic glomerulonephritis, but whether effector Th17 cells also contribute is unknown. We compared the involvement of Th1 and Th17 cells in a mouse model of antigen-specific glomerulonephritis in which effector CD4+ cells are the only components of adaptive immunity that induce injury. We planted the antigen ovalbumin on the glomerular basement membrane of Rag1(-/-) mice using an ovalbumin-conjugated non-nephritogenic IgG1 monoclonal antibody against alpha3(IV) collagen. Subsequent injection of either Th1- or Th17-polarized ovalbumin-specific CD4+ effector cells induced proliferative glomerulonephritis. Mice injected with Th1 cells developed progressive albuminuria over 21 d, histologic injury including 5.5 +/- 0.9% crescent formation/segmental necrosis, elevated urinary nitrate, and increased renal NOS2, CCL2, and CCL5 mRNA. Mice injected with Th17 cells developed albuminuria by 3 d; compared with Th1-injected mice, their glomeruli contained more neutrophils and greater expression of renal CXCL1 mRNA. In conclusion, Th1 and Th17 effector cells can induce glomerular injury. Understanding how these two subsets mediate proliferative forms of glomerulonephritis may lead to targeted therapies. PMID:19820122

  5. The SWI/SNF ATPase Brm is a gatekeeper of proliferative control in prostate cancer.

    Science.gov (United States)

    Shen, Hui; Powers, Nathan; Saini, Nitin; Comstock, Clay E S; Sharma, Ankur; Weaver, Katherine; Revelo, Monica P; Gerald, William; Williams, Erin; Jessen, Walter J; Aronow, Bruce J; Rosson, Gary; Weissman, Bernard; Muchardt, Christian; Yaniv, Moshe; Knudsen, Karen E

    2008-12-15

    Factors that drive prostate cancer progression remain poorly defined, thus hindering the development of new therapeutic strategies. Disseminated tumors are treated through regimens that ablate androgen signaling, as prostate cancer cells require androgen for growth and survival. However, recurrent, incurable tumors that have bypassed the androgen requirement ultimately arise. This study reveals that the Brm ATPase, a component of selected SWI/SNF complexes, has significant antiproliferative functions in the prostate that protect against these transitions. First, we show that targeted ablation of Brm is causative for the development of prostatic hyperplasia in mice. Second, in vivo challenge revealed that Brm-/- epithelia acquire the capacity for lobe-specific, castration-resistant cellular proliferation. Third, investigation of human specimens revealed that Brm mRNA and protein levels are attenuated in prostate cancer. Fourth, Brm down-regulation was associated with an increased proliferative index, consistent with the mouse model. Lastly, gene expression profiling showed that Brm loss alters factors upstream of E2F1; this was confirmed in murine models, wherein Brm loss induced E2F1 deregulation in a tissue-specific manner. Combined, these data identify Brm as a major effector of serum androgen-induced proliferation in the prostate that is disrupted in human disease, and indicate that loss of Brm confers a proliferative advantage in prostate cancer. PMID:19074882

  6. Early pathogenesis in porcine proliferative enteropathy caused by Lawsonia intracellularis

    DEFF Research Database (Denmark)

    Boutrup, Torsten Snogdal; Boesen, H. T.; Boye, Mette;

    2010-01-01

    The intestinal bacterium Lawsonia intracellularis, the cause of proliferative enteropathy (PE) in pigs, is believed to infect mitotically active epithelial cells of the intestinal crypts and then multiply and spread in these cells as they divide. Further spread of infection is thought to occur by...... enterocytes. Furthermore, early invasion of the intestinal connective tissue was observed; with the presence of single bacteria in the lamina propria 12 hpi, and with a further spread of bacteria in the lamina propria observed at 5 dpi, suggesting an active role for the lamina propria in the course of...

  7. Anti-proliferative evaluation of monoterpene derivatives against leukemia.

    Science.gov (United States)

    Gautam, Lekh Nath; Ling, Taotao; Lang, Walter; Rivas, Fatima

    2016-05-01

    The cure rate of pediatric acute lymphoblastic leukemia (ALL) has significantly improved in the past thirty years, however not all patient cohorts respond well to current chemotherapy regimens. Among the high risk patient cohort is infants with MLL-rearranged (MLL-r) B-ALL, which remains dismal with an overall survival rate treatments. Based on a phenotypic screen, phenolic natural products were identified as promising scaffolds for further chemical evaluation. Herein we disclose the effects of a potent anti-proliferative compound 31 against human ALL leukemia cellular models. PMID:26922230

  8. Comments on 'Standard effective doses for proliferative tumours'

    International Nuclear Information System (INIS)

    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 BED10 or BED3 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 (PSED1) in which the proliferation correction is applied in the altered schedule, but not in the standard schedule; (b) the proliferative standard effective dose two (PSED2) 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 (PSED2) (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 some

  9. Hepatic progenitor cell resistance to TGF-β1's proliferative and apoptotic effects

    International Nuclear Information System (INIS)

    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

  10. A descriptive study of the frequency and characteristics of proliferative enteropathy in swine in Ontario by analyzing routine animal health surveillance data.

    OpenAIRE

    Wilson, J. B.; Pauling, G E; McEwen, B J; Smart, N; Carman, P. S.; Dick, C P

    1999-01-01

    Routine surveillance data, collected on pathology submissions at the Animal Health Laboratory in Guelph between 1992 and 1997, were analyzed to determine demographic, clinical, and pathologic characteristics of cases of proliferative enteropathy and the frequency of this condition relative to other infectious enteric diseases in swine in Ontario. The most commonly reported disease was Escherichia coli enteritis (average cases/year = 70.0). Among infectious enteropathies that occur typically i...

  11. Proliferative glomerulonephritis with monoclonal immunoglobulin G deposits complicated by immunoglobulin A nephropathy in the renal allograft.

    Science.gov (United States)

    Sawada, Anri; Kawanishi, Kunio; Horita, Shigeru; Koike, Junki; Honda, Kazuho; Ochi, Ayami; Komoda, Mizuki; Tanaka, Yoichiro; Unagami, Kohei; Okumi, Masayoshi; Shimizu, Tomokazu; Ishida, Hideki; Tanabe, Kazunari; Nagashima, Yoji; Nitta, Kosaku

    2016-07-01

    Immunoglobulin (Ig) A nephropathy (IgAN) is a known autoimmune disease due to abnormal glycosylation of IgA1, and occasionally, IgG co-deposition occurs. The prognosis of IgG co-deposition with IgAN is adverse, as shown in the previous studies. However, in the clinical setting, monoclonality of IgG co-deposition with IgAN has not been observed. We describe a case of proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) combined with IgAN in a renal allograft. A-21-year-old man developed end-stage renal failure with unknown aetiology and underwent living-donor kidney transplantation from his mother 2 years after being diagnosed. One year after kidney transplantation, proteinuria 2+ and haematuria 2+ were detected; allograft biopsy revealed mesangial IgA and C3 deposits, indicating a diagnosis of IgAN. After tonsillectomy and steroid pulse therapy, proteinuria and haematuria resolved. However, 4 years after transplantation, pedal oedema, proteinuria (6.89 g/day) and allograft dysfunction (serum creatinine (sCr) 203.3 µmol/L) appeared. A second allograft biopsy showed mesangial expansion and focal segmental proliferative endocapillary lesions with IgA1λ and monoclonal IgG1κ depositions. Electron microscopic analysis revealed a massive amount of deposits, located in the mesangial and subendothelial lesions. A diagnosis of PGNMID complicated with IgAN was made, and rituximab and plasmapheresis were added to steroid pulse therapy. With this treatment, proteinuria was alleviated to 0.5 g/day, and the allograft dysfunction recovered to sCr 132.6 µmol/L. This case suggests a necessity for investigation of PGNMID and IgA nephropathy in renal allografts to detect monoclonal Ig deposition disease. PMID:26971743

  12. Arsenic-induced promoter hypomethylation and over-expression of ERCC2 reduces DNA repair capacity in humans by non-disjunction of the ERCC2-Cdk7 complex.

    Science.gov (United States)

    Paul, Somnath; Banerjee, Nilanjana; Chatterjee, Aditi; Sau, Tanmoy J; Das, Jayanta K; Mishra, Prafulla K; Chakrabarti, Partha; Bandyopadhyay, Arun; Giri, Ashok K

    2014-04-01

    Arsenic in drinking water is of critical concern in West Bengal, India, as it results in several physiological symptoms including dermatological lesions and cancers. Impairment of the DNA repair mechanism has been associated with arsenic-induced genetic damage as well as with several cancers. ERCC2 (Excision Repair Cross-Complementing rodent repair, complementation group 2), mediates DNA-repair by interacting with Cdk-activating kinase (CAK) complex, which helps in DNA proof-reading during transcription. Arsenic metabolism alters epigenetic regulation; we tried to elucidate the regulation of ERCC2 in arsenic-exposed humans. Water, urine, nails, hair and blood samples from one hundred and fifty seven exposed and eighty eight unexposed individuals were collected. Dose dependent validation was done in vitro using HepG2 and HEK-293. Arsenic content in the biological samples was higher in the exposed individuals compared with the content in unexposed individuals (p < 0.001). Bisulfite-modified methylation specific PCR showed a significant (p < 0.0001) hypomethylation of the ERCC2 promoter in the arsenic-exposed individuals. Densitometric analysis of immunoblots showed a nearly two-fold increase in expression of ERCC2 in exposed individuals, but there was an enhanced genotoxic insult as measured by micronuclei frequency. Immuno-precipitation and western blotting revealed an increased (p < 0.001) association of Cdk7 with ERCC2 in highly arsenic exposed individuals. The decrease in CAK activity was determined by observing the intensity of Ser(392) phosphorylation in p53, in vitro, which decreased with an increase in arsenic dose. Thus we infer that arsenic biotransformation leads to promoter hypomethylation of ERCC2, which in turn inhibits the normal functioning of the CAK-complex, thus affecting DNA-repair; this effect was highest among the arsenic exposed individuals with dermatological lesions. PMID:24473091

  13. Expression of CD133 in various premalignant and proliferative lesions

    Directory of Open Access Journals (Sweden)

    Rahmi Amtha

    2015-06-01

    Full Text Available Background: In Jakarta, oral squamous cell carcinoma (OSCC usually detected in late stage with very low survival rate ofabout 1.1 years. OSCC may be preceded by premalignant lesion, so that early detection of the lesion may decrease the mortality rate due to oral malignancy. CD133 is a hematopoietic stem cell that play role in tissue regeneration, inflammation and tumor. Upregulated of CD133 was reported on tumor progression. Purpose: The aim of study is to determine circulating CD133 expression on premalignant (PML and proliferative (PL lesion. Method: Observational research was carried out on patients who seek treatment of PML and PL at Oral Medicine clinic. CD133 was taken from peripheral blood serum, examined using PCR. Data was analyzed by Chi square test. Result: 15 subjects (each of five subjects for PML, PL and control consist of 40% male and 60% female. Age group of above 41 years old was most affected PML and PL (66.7%. Tongue is common site for oral lesion (40%. There is a significant different of circulating CD133 rate among all groups lesion (p=0.039. Conclusion: CD133 express differently in premalignant and proliferative lesions.

  14. Sequence stratigraphic control on prolific HC reservoir development, Southwest Iran

    Science.gov (United States)

    Lasemi, Y.; Kondroud, K.N.

    2008-01-01

    An important carbonate formation in the Persian Gulf and the onshore oil fields of Southwest Iran is the Lowermost Cretaceous Fahliyan formation. The formation in Darkhowain field consists of unconformity-bounded depositional sequences containing prolific hydrocarbon reservoirs of contrasting origin. Located in the high stand systems tract (HST) of the lower sequence encompassing over 200m of oil column are the most prolific reservoir. Another reservoir is over 80m thick consisting of shallowing-upward cycles that are best developed within the transgressive systems tract of the upper sequence. Vertical facies distribution and their paleobathymetry and geophysical log signatures of the Fahliyan formation in the Darkhowain platform reveal the presence of two unconformity-bounded depositional sequences in Vail et al., Van Wagoner et al., and Sarg. The Fahliyan formation mainly consists of platform carbonates composed of restricted bioclastic lime mudstone to packstone of the platform interior, Lithocodium boundstone or ooid-intraclast-bioclast grainstone of the high energy platform margin and the bioclast packstone to lime mudstone related to the off-platform setting.

  15. Potentiation of lymphocyte proliferative responses by nickel sulfide

    Science.gov (United States)

    Jaramillo, A.; Sonnenfeld, G.

    1992-01-01

    Crystalline nickel sulfide (NiS) induced a spleen cell proliferation that resembles a mixed lymphocyte reaction (MLR). It depended on cell-cell interaction, induced high levels of interleukin-1 (IL-1) and interleukin-2 (IL-2) and the responding cell subpopulation was composed of CD4+ T lymphocytes. Furthermore, the proliferation was inhibited in a dose-dependent manner by magnesium. Crystalline NiS also increased significantly the spleen cell proliferative response to concanavalin A (Con A) and lipopolysaccharide (LPS) with magnesium potentiating the combined effects of crystalline NiS and mitogens. Interestingly, crystalline NiS did not show any effect on the induction of IL-2 by Con A. The results described herein suggest that crystalline NiS can potentiate both antigenic (MLR) and mitogenic (Con A and LPS) proliferative responses in vitro. Crystalline NiS appears to potentiate these responses by acting in the form of ionic nickel on several intracellular targets for which magnesium ions have different noncompetitive interactions. The effects of magnesium on the potentiating action of crystalline NiS are different depending upon the type of primary stimulatory signal for proliferation (mitogenic or antigenic).

  16. Heterogeneity in proliferative potential of ovine mesenchymal stem cell colonies.

    Science.gov (United States)

    Rhodes, N P; Srivastava, J K; Smith, R F; Longinotti, C

    2004-04-01

    Bone marrow biopsies were taken from the iliac crest of 28 individual sheep from three different breeds, ranging in age from 4 months to 8 years and mesenchymal stem cells (MSCs) isolated using selection due to plastic adherence. Cells were cultured in medium that had been selected for its effect on observed MSC proliferation, until populations of greater than 50 million had been obtained from each biopsy. The identity of the isolated cell populations as progenitors of the mesenchymal lineage was verified by deriving both osteoblastic and chondrocytic phenotypes when cultured in osteogenic and chondrogenic medium supplements, respectively. The rate of cell proliferation for each marrow biopsy was measured at each passage and the number of initial stem cells in each sample estimated. There was no statistically significant correlation between the age of the sheep and MSC proliferative potential, or age and estimated initial MSC number. There was no apparent significant difference between proliferation rate and sheep breed and colonies established from frozen cells grew at similar rates to pre-frozen cells. Counter intuitively, there appeared to be a negatively correlated trend between proliferation rate and MSC concentration in the samples. It is concluded that no initial descriptive statistics of the marrow biopsies can assist in estimating the proliferative potential, and therefore the timing of future surgeries, of MSCs sampled for the purposes of tissue engineering. PMID:15332606

  17. Immunohistochemical analysis of Metadherin in proliferative and cancerous breast tissue

    Directory of Open Access Journals (Sweden)

    Zhang Qinghui

    2010-06-01

    Full Text Available Abstract Background Metadherin (MTDH has been reported to be associated with cancer progression in various types of human cancers including breast cancer. Whether MTDH contributes to carcinogenesis of breast cancer is still unknown. In the present study, we investigated the expression of MTDH in normal, UDH (usual ductal hyperplasia, ADH (atypical ductal hyperplasia, DCIS (ductal carcinoma in situ and invasive cancer to explore the possible role of MTDH for breast cancer carcinogenesis. Methods Immunohistochemistry was employed on paraffin sections of surgical removed breast samples. Results The immunohistochemical results showed almost no staining in normal tissue, moderate staining in ADH and UDH, intense MTDH stains in DCIS and cancer. Statistical analysis demonstrated significant different MTDH expression between proliferative and cancerous breast lesions (p p = 0.028. In breast cancer, statistical analysis revealed a significant correlation between MTDH expression with patients' age (p = 0.042, ER status (p = 0.018 and p53 status (p = 0.001. We also examined the effect of MTDH on cell proliferation in DCIS and cancer, and we found that MTDH overexpression was significantly correlated with high Ki67 index (p = 0.008 and p = 0.036, respectively. Conclusions MTDH overexpression could be identified in proliferative breast lesions and may contribute to breast cancer progression.

  18. Anti-proliferative effect of Ficus pumila Linn. on human leukemic cell lines

    Directory of Open Access Journals (Sweden)

    Christopher Larbie

    2015-04-01

    Conclusion: These findings suggest that crude extracts of FPS and FPL have anti-proliferative effect on the leukemia cells. The antioxidant properties of the plant including phenolics may be partly responsible for the anti-proliferative activity. Further studies are required to isolate chemical components of the plant and establish their anti-proliferative activities and mechanism of action. [Int J Basic Clin Pharmacol 2015; 4(2.000: 330-336

  19. Insulin-sensitizing and anti-proliferative effects of Argania spinosa seed extracts.

    Science.gov (United States)

    Samane, Samira; Noël, Josette; Charrouf, Zoubida; Amarouch, Hamid; Haddad, Pierre Selim

    2006-09-01

    Argania spinosa is an evergreen tree endemic of southwestern Morocco. Many preparations have been used in traditional Moroccan medicine for centuries to treat several illnesses including diabetes. However, scientific evidence supporting these actions is lacking. Therefore, we prepared various extracts of the argan fruit, namely keel, cake and argan oil extracts, which we tested in the HTC hepatoma cell line for their potential to affect cellular insulin responses. Cell viability was measured by Trypan Blue exclusion and the response to insulin evaluated by the activation of the extracellular regulated kinase (ERK1/2), ERK kinase (MEK1/2) and protein kinase B (PKB/Akt) signaling components. None of the extracts demonstrated significant cytotoxic activity. Certain extracts demonstrated a bi-phasic effect on ERK1/2 activation; low doses of the extract slightly increased ERK1/2 activation in response to insulin, whereas higher doses completely abolished the response. In contrast, none of the extracts had any significant effect on MEK whereas only a cake saponin subfraction enhanced insulin-induced PKB/Akt activation. The specific action of argan oil extracts on ERK1/2 activation made us consider an anti-proliferative action. We have thus tested other transformed cell lines (HT-1080 and MSV-MDCK-INV cells) and found similar results. Inhibition of ERK1/2 activation was also associated with decreased DNA synthesis as evidenced by [(3)H]thymidine incorporation experiments. These results suggest that the products of Argania spinosa may provide a new therapeutic avenue against proliferative diseases. PMID:16951716

  20. Postirradiation proliferative activity and morphology of human bone marrow

    International Nuclear Information System (INIS)

    Bone marrow cells distribution by cell cycle stages (S, G1/0, G2+M) were studied by flow cytometry and myelograms analyzed in 13 subjects occupationally irradiated during an emergency situation, in 19 patients administered radiotherapy, and in 26 normal subjects. Low-dose (0,2 to 0,4 Gy) exposure was associated with an increase of proliferative activity, higher doses (1 to 4 Gy) caused a reduction of the share of cells in the phase of DNA synthesis and an expressed block at the C2+M stage. The studied parameters of cellular cycle reflect the degree of radiation exposure and together with myelogram values may be regarded as diagnostic characteristics of hemopoiesis. 10 refs., 4 figs., 1 tab

  1. Anticardiolipin antibodies in proliferative diabetic retinopathy: An additional risk factor

    International Nuclear Information System (INIS)

    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)

  2. Anti proliferative activity of hydnophytum formicarium (sanola) extracts

    International Nuclear Information System (INIS)

    The whole plant of Hydnophytum formicarium Jack (Rubiaceae) locally known as sarang semut, was first extracted successively by petroleum-ether, followed by methanol (MeOH), chloroform, n-buthanol and distilled water and were tested for anti proliferative activity using a panel of human cancer cell lines. MeOH, n-buthanol and aqueous extracts showed anti proliferative effect towards KB-IV (EC50 methanol extract: 17.58 μg/ml; EC50 n-buthanol extract: 9.12 μg/ml and EC50 aqueous extract: 8.71 μg/ml) and only methanol extract showed positive activity towards Caov-3 (EC50: 14.79 μg/ml). No activity was observed in case of other extracts (i.e. petroleum ether and chloroform with EC50 >99 μg/ml). The methanolic extract was tested for its mechanism of action via apoptosis on Caov-3 by employing the TUNEL assay. In the present study, augmented levels of apoptosis were observed in Caov-3 cells treated with 15 μg/ml with apoptotic index of 43.3% and 78.8% in higher concentration (20 μg/ml), a significant different compared with control, which had apoptotic index of 2% only. In conclusion, there is a high possibility that the bioactive component in the methanol extract had selective anti proliferation effects on Caov-3 through apoptotic pathway. This finding may provide a new strategy and a promising approach to the discovery an effective anticancer drug. (Author)

  3. Quiescent and proliferative fibroblasts exhibit differential p300 HAT activation through control of 5-methoxytryptophan production.

    Directory of Open Access Journals (Sweden)

    Huei-Hsuan Cheng

    Full Text Available Quiescent fibroblasts possess unique genetic program and exhibit high metabolic activity distinct from proliferative fibroblasts. In response to inflammatory stimulation, quiescent fibroblasts are more active in expressing cyclooxygenase-2 and other proinflammatory genes than proliferative fibroblasts. The underlying transcriptional mechanism is unclear. Here we show that phorbol 12-myristate 13-acetate (PMA and cytokines increased p300 histone acetyltransferase activity to a higher magnitude (> 2 fold in quiescent fibroblasts than in proliferative fibroblasts. Binding of p300 to cyclooxygenase-2 promoter was reduced in proliferative fibroblasts. By ultrahigh-performance liquid chromatography coupled with a quadrupole time of flight mass spectrometer and enzyme-immunoassay, we found that production of 5-methoxytryptophan was 2-3 folds higher in proliferative fibroblasts than that in quiescent fibroblasts. Addition of 5-methoxytryptophan and its metabolic precursor, 5-hydroxytryptophan, to quiescent fibroblasts suppressed PMA-induced p300 histone acetyltransferase activity and cyclooxygenase-2 expression to the level of proliferative fibroblasts. Silencing of tryptophan hydroxylase-1 or hydroxyindole O-methyltransferase in proliferative fibroblasts with siRNA resulted in elevation of PMA-induced p300 histone acetyltransferase activity to the level of that in quiescent fibroblasts, which was rescued by addition of 5-hydroxytryptophan or 5-methoxytryptophan. Our findings indicate that robust inflammatory gene expression in quiescent fibroblasts vs. proliferative fibroblasts is attributed to uncontrolled p300 histone acetyltransferase activation due to deficiency of 5-methoxytryptophan production. 5-methoxytryptophan thus is a potential valuable lead compound for new anti-inflammatory drug development.

  4. Proliferative activity of adrenal glands with adrenocortical cytomegaly measured by MIB-1 labeling index.

    Science.gov (United States)

    Fasano, M; Greco, M A

    1996-01-01

    To investigate the proliferative activity of cytomegalic cells in the fetal adrenal cortex, we studied adrenal glands with cytomegaly by immunohistochemistry using the nuclear proliferation maker MIB-1. The percentage of positively stained nuclei was quantified using the SAMBA 4000 image analysis system. Only one case showed occasional positively stained cytomegalic cell nuclei. The permanent cortices showed proliferative activity that decreased with increasing gestational age. No proliferative activity was seen in normal fetal cortices except in one case that received corticosteroid therapy and had a maternal history of diabetes. The near absence of proliferative activity of the cytomegalic cells supports the previously proposed theory of cellular exhaustion following hyperactivity. The high proliferative activity in the fetal cortex of the infant receiving corticosteroid therapy may provide insight into the stimulus causing the hypermetabolic state. PMID:9025875

  5. Identification and characterization of proliferative retinopathy-related long noncoding RNAs

    International Nuclear Information System (INIS)

    Proliferative vitreoretinopathy (PVR) is a serious complication of retinal detachment and vitreoretinal surgery, which can lead to severe vision reduction. Long non-coding RNAs (lncRNAs) play critical roles in many biological processes and disease development. We attempted to determine the role of lncRNAs in the setting of PVR. Microarray analysis revealed that 78 lncRNAs were abnormally expressed in the epiretinal membranes (ERMs) of PVR patients, including 48 up-regulated and 30 down-regulated lncRNA transcripts. We subsequently focus on one lncRNA, MALAT1, and investigated its expression pattern in the biofluid of PVR patients. MALAT1 was significantly up-regulated in the cellular and plasma fraction of peripheral blood in PVR patients. MALAT1 expression was obviously reduced after PVR operation. In vitro experiments revealed the role of MALAT1 in regulating RPE proliferation and migration, which is critical for ERMs formation. This study suggests that lncRNAs are the potential regulators of PVR pathology. MALAT1 is a potential prognostic indicator and a target for the diagnosis and gene therapy for PVR diseases. - Highlights: • 78 lncRNAs are differentially expressed between PVR-ERMs and secondary ERMs. • MALAT1 level is elevated in the ERMs of PVR patients. • Circulating MALAT1 level is up-regulated in PVR patients. • MALAT1 knockdown regulates RPE proliferation and migration

  6. Identification and characterization of proliferative retinopathy-related long noncoding RNAs

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Rong-Mei; Wang, Xiao-Qun; Yao, Jin [Eye Hospital, Nanjing Medical University, Nanjing (China); The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing (China); Shen, Yi; Chen, Sai-Nan [Eye Hospital, Nanjing Medical University, Nanjing (China); Yang, Hong [Eye Hospital, Nanjing Medical University, Nanjing (China); The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing (China); Jiang, Qin, E-mail: jqin710@vip.sina.com [Eye Hospital, Nanjing Medical University, Nanjing (China); The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing (China); Institute of Integrated Medicine, Nanjing Medical University, Nanjing (China); Yan, Biao, E-mail: yanbiao1982@hotmail.com [Eye Hospital, Nanjing Medical University, Nanjing (China); The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing (China); Institute of Integrated Medicine, Nanjing Medical University, Nanjing (China)

    2015-09-25

    Proliferative vitreoretinopathy (PVR) is a serious complication of retinal detachment and vitreoretinal surgery, which can lead to severe vision reduction. Long non-coding RNAs (lncRNAs) play critical roles in many biological processes and disease development. We attempted to determine the role of lncRNAs in the setting of PVR. Microarray analysis revealed that 78 lncRNAs were abnormally expressed in the epiretinal membranes (ERMs) of PVR patients, including 48 up-regulated and 30 down-regulated lncRNA transcripts. We subsequently focus on one lncRNA, MALAT1, and investigated its expression pattern in the biofluid of PVR patients. MALAT1 was significantly up-regulated in the cellular and plasma fraction of peripheral blood in PVR patients. MALAT1 expression was obviously reduced after PVR operation. In vitro experiments revealed the role of MALAT1 in regulating RPE proliferation and migration, which is critical for ERMs formation. This study suggests that lncRNAs are the potential regulators of PVR pathology. MALAT1 is a potential prognostic indicator and a target for the diagnosis and gene therapy for PVR diseases. - Highlights: • 78 lncRNAs are differentially expressed between PVR-ERMs and secondary ERMs. • MALAT1 level is elevated in the ERMs of PVR patients. • Circulating MALAT1 level is up-regulated in PVR patients. • MALAT1 knockdown regulates RPE proliferation and migration.

  7. Aquaporin-1 Expression in Proliferative Vitreoretinopathy and in Epiretinal Membranes

    Directory of Open Access Journals (Sweden)

    Elie Motulsky

    2014-01-01

    Full Text Available Purpose. Aquaporin-1 (AQP1 is involved in cell migration and proliferation; therefore, the purpose of the study was to investigate its expression in proliferative vitreoretinopathy (PVR and epiretinal membranes (ERM. Methods. 19 membranes from PVR and ERM were collected following eye surgery. AQP1 mRNA and protein expressions were determined by RT-qPCR and immunofluorescence in the membranes from PVR and ERM. Results. AQP1 mRNA and protein were expressed in both PVR and ERM as shown by RT-qPCR and immunofluorescence. AQP1 protein expression was heterogeneous among and between PVR and ERM and colocalized with alpha-smooth muscle actin (αSMA and with glial fibrillary acidic protein (GFAP. There were a higher percentage of cells coexpressing AQP1 and αSMA than AQP1 and GFAP. GFAP and αSMA did not colocalize. Conclusion. Our data show for the first time AQP1 expression in both PVR and ERM. AQP1 is expressed mostly by the αSMA-positive cells, presumably myofibroblasts, but also by GFAP-positive cells, assumed to be glial cells. These original findings warrant further functional investigations aiming at studying the potential role of AQP1 in cell migration and proliferation occurring during the development of PVR and ERM.

  8. 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.

  9. Outcome of the acute glomerular injury in proliferative lupus nephritis

    International Nuclear Information System (INIS)

    Treatment with total lymphoid irradiation (TLI) and corticosteroids markedly reduced activity of systemic lupus erythematosis in 10 patients with diffuse proliferative lupus nephritis (DPLN) complicated by a nephrotic syndrome. Physiologic and morphometric techniques were used serially before, and 12 and 36 mo post-TLI to characterize the course of glomerular injury. Judged by a progressive reduction in the density of glomerular cells and immune deposits, glomerular inflammation subsided. A sustained reduction in the fractional clearance of albumin, IgG and uncharged dextrans of radius greater than 50 A, pointed to a parallel improvement in glomerular barrier size-selectivity. Corresponding changes in GFR were modest, however. A trend towards higher GFR at 12 mo was associated with a marked increase in the fraction of glomerular tuft area occupied by patent capillary loops as inflammatory changes receded. A late trend toward declining GFR beyond 12 mo was associated with progressive glomerulosclerosis, which affected 57% of all glomeruli globally by 36 mo post-TLI. Judged by a parallel increase in volume by 59%, remaining, patent glomeruli had undergone a process of adaptive enlargement. We propose that an increasing fraction of glomeruli continues to undergo progressive sclerosis after DPLN has become quiescent, and that the prevailing GFR depends on the extent to which hypertrophied remnant glomeruli can compensate for the ensuing loss of filtration surface area

  10. Intense Pulsed-Light Therapy for Proliferative Haemangiomas of Infancy

    Directory of Open Access Journals (Sweden)

    Marie Caucanas

    2011-01-01

    Full Text Available Infantile haemangioma therapy has long been a wait-and-see policy. Since recent development of laser and light therapy, pulsed dye laser has been successfully used for treating superficial haemangiomas. Few studies have been published about treatment with intense pulsed light (IPL to assess the risk/benefit of IPL in the treatment of infantile haemangiomas during their early proliferative phase. In the present retrospective cohort study, we retrieved data about a series of 14 Caucasian children (median age: 4.8 months with infantile haemangiomas treated with Photoderm Vasculight flash lamp. All patients experienced a rapid regression of the haemangiomas after 3 treatments on average. Few adverse events were noted, including ulceration and crusts. No residual scarring and cosmetic damages were noticed. Fast growing haemangiomas should be treated with light therapy as soon as possible. This technology is safe, efficient, inducing regression, and preventing any further functional and aesthetic complications. The benefit-risk ratio favours the treatment of most types of haemangiomas which are out of the scope of betablocker administration.

  11. Outcome of the acute glomerular injury in proliferative lupus nephritis

    Energy Technology Data Exchange (ETDEWEB)

    Chagnac, A.; Kiberd, B.A.; Farinas, M.C.; Strober, S.; Sibley, R.K.; Hoppe, R.; Myers, B.D. (Stanford Univ. Medical Center, CA (USA))

    1989-09-01

    Treatment with total lymphoid irradiation (TLI) and corticosteroids markedly reduced activity of systemic lupus erythematosis in 10 patients with diffuse proliferative lupus nephritis (DPLN) complicated by a nephrotic syndrome. Physiologic and morphometric techniques were used serially before, and 12 and 36 mo post-TLI to characterize the course of glomerular injury. Judged by a progressive reduction in the density of glomerular cells and immune deposits, glomerular inflammation subsided. A sustained reduction in the fractional clearance of albumin, IgG and uncharged dextrans of radius greater than 50 A, pointed to a parallel improvement in glomerular barrier size-selectivity. Corresponding changes in GFR were modest, however. A trend towards higher GFR at 12 mo was associated with a marked increase in the fraction of glomerular tuft area occupied by patent capillary loops as inflammatory changes receded. A late trend toward declining GFR beyond 12 mo was associated with progressive glomerulosclerosis, which affected 57% of all glomeruli globally by 36 mo post-TLI. Judged by a parallel increase in volume by 59%, remaining, patent glomeruli had undergone a process of adaptive enlargement. We propose that an increasing fraction of glomeruli continues to undergo progressive sclerosis after DPLN has become quiescent, and that the prevailing GFR depends on the extent to which hypertrophied remnant glomeruli can compensate for the ensuing loss of filtration surface area.

  12. Synthesis and Anti-Proliferative Effects of Quercetin Derivatives.

    Science.gov (United States)

    Al-Jabban, Sami M R; Zhang, Xiaojie; Chen, Guanglin; Mekuria, Ermias Addo; Rakotondraibe, Liva Harinantenaina; Chen, Qiao-Hong

    2015-12-01

    Prostate cancer is the most common diagnosed invasive cancer in American men and is the second leading cause of cancer-related deaths. Although there are several therapies successful in treating early, localized stage prostate cancer, current treatment of advanced metastatic castration-resistant prostate cancer remains ineffective due to inevitable progression of resistance to first-line treatment with docetaxel. The natural product quercetin (3,3',4',5,7-pentahydroxyflavone), a flavonoid compound ubiquitous in dietary plants, possesses evidenced potential in treating advanced metastatic castration-resistant prostate cancer. However, its poor bioavailability and moderate potency hinder its advancement into clinical therapy. In order to engineer quercetin derivatives with improved potency and pharmacokinetic profiles for the treatment of advanced metastatic prostate cancer, we started this study with creating a small library of alkylated derivatives of quercetin for in vitro evaluation. The biological data and chemical reactivity of quercetin and its derivatives reported in literature directed us to design 3,4',7-O-trialkylquercetins as our first batch of targets. Consequently, nine 3,4',7-O-trialkylquercetins, together with four 3,7-O- dialkylquercetins, four 3,3',4',7-tetraalkylquercetins, and one 3,3',4'-O-trialkylquercetin, were prepared by one step O-alkylation of commercially available quercetin mediated by potassium carbonate. Their structures were determined by ID and 2D NMR data, and HRMS. Their anti-proliferative activities towards both androgen-refractory and androgen-sensitive prostate cancer cells were evaluated using WST-1 cell proliferation assay. The acquired structure-activity relationships indicate that 3,7-O-dialkylquercetins rather than 3,4',7-O-trialkylquercetins were much more potent than quercetin towards prostate cancer cells. PMID:26882678

  13. Oral proliferative verrucous leucoplakia: are there particular features for such an ambiguous entity? A systematic review.

    Science.gov (United States)

    Pentenero, M; Meleti, M; Vescovi, P; Gandolfo, S

    2014-05-01

    Proliferative verrucous leucoplakia (PVL) is a distinct, particularly aggressive form of oral leucoplakia. Given the low prevalence of PVL, data are sparse and are mostly from case reports, case series and only a few case-control studies, meaning that the literature is able to provide only weak evidence. The present systematic literature review aims to collate the available evidence on the following issues: patient demographics, aetiology, lesion location(s), malignant potential, location and histopathological features of transformed lesions, disease-specific survival rates and treatment response. Electronic databases were searched for studies in the English language reporting original data from at least 10 patients with PVL on the target issues of the present review. The retrieved data were merged and a descriptive analysis performed. The 20 studies selected indicated that PVL does not seem to be correlated with the major risk factors for oral carcinoma (tobacco, alcohol and/or areca nut/betel leaf chewing). The disorder affects mainly adult/elderly women and has a very high malignant transformation rate, particular site distribution and particular location and histopathological features of transformed lesions. The present results may be limited by some articles being unintentionally excluded as they were not found during the electronic search, a lack of worldwide accepted diagnostic criteria for PVL, and overlapping data from multiple studies performed in a limited number of centres. Despite these potential drawbacks, the present results demonstrate that PVL does have particular features. PMID:24471527

  14. Immunophenotyping and T-cell proliferative capacity in a healthy aged population.

    Science.gov (United States)

    Peres, Alessandra; Bauer, Moisés; da Cruz, Ivana Beatrice; Nardi, Nance Beyer; Chies, José Artur Bogo

    2003-01-01

    The age-related decline of immunological functions is well established but it remains largely unknown which specific changes are related to disease. We analyzed peripheral blood lymphocytes of 42 healthy elderly as well as 24 healthy young subjects from southern Brazil. No differences in phytohemagglutinin-induced proliferation and CD4:CD8 ratio were found between the subjects. However, CD4 expression (considering mean fluorescence intensity) was found upregulated in elderly subjects. No changes in activation molecules CD25, CD28, CD69 and CD95 were observed. A reduced proportion of naive (CD45RA+) T cells was found in the elderly compared to young subjects. No changes in adhesion molecule expression (CD11c and CD31) were observed. However, the frequencies of CD49d-positive cells, as well as expression of CD62L, were increased in the eldery subjects. We further described two subgroups of eldery subjects with an immunological risk profile defined by lower CD4:CD8 ratio and reduced proliferative response to mitogens. These data suggest that healthy aging is associated with intact T-cell proliferation and some compensatory immunophenotypical changes. PMID:14618026

  15. Chronic Renal Transplant Rejection and Possible Anti-Proliferative Drug Targets.

    Science.gov (United States)

    Bhatti, Adnan Bashir; Usman, Muhammad

    2015-01-01

    The global prevalence of renal transplants is increasing with time, and renal transplantation is the only definite treatment for end-stage renal disease. We have limited the acute and late acute rejection of kidney allografts, but the long-term survival of renal tissues still remains a difficult and unanswered question as most of the renal transplants undergo failure within a decade of their transplantation. Among various histopathological changes that signify chronic allograft nephropathy (CAN), tubular atrophy, fibrous thickening of the arteries, fibrosis of the kidney interstitium, and glomerulosclerosis are the most important. Moreover, these structural changes are followed by a decline in the kidney function as well. The underlying mechanism that triggers the long-term rejection of renal transplants involves both humoral and cell-mediated immunity. T cells, with their related cytokines, cause tissue damage. In addition, CD 20+ B cells and their antibodies play an important role in the long-term graft rejection. Other risk factors that predispose a recipient to long-term graft rejection include HLA-mismatching, acute episodes of graft rejection, mismatch in donor-recipient age, and smoking. The purpose of this review article is the analyze current literature and find different anti-proliferative agents that can suppress the immune system and can thus contribute to the long-term survival of renal transplants. The findings of this review paper can be helpful in understanding the long-term survival of renal transplants and various ways to improve it. PMID:26677426

  16. Neuroretinal hypoxic signaling in a new preclinical murine model for proliferative diabetic retinopathy

    Science.gov (United States)

    Wert, Katherine J; Mahajan, Vinit B; Zhang, Lijuan; Yan, Yuanqing; Li, Yao; Tosi, Joaquin; Hsu, Chun Wei; Nagasaki, Takayuki; Janisch, Kerstin M; Grant, Maria B; Mahajan, MaryAnn; Bassuk, Alexander G; Tsang, Stephen H

    2016-01-01

    Diabetic retinopathy (DR) affects approximately one-third of diabetic patients and, if left untreated, progresses to proliferative DR (PDR) with associated vitreous hemorrhage, retinal detachment, iris neovascularization, glaucoma and irreversible blindness. In vitreous samples of human patients with PDR, we found elevated levels of hypoxia inducible factor 1 alpha (HIF1α). HIFs are transcription factors that promote hypoxia adaptation and have important functional roles in a wide range of ischemic and inflammatory diseases. To recreate the human PDR phenotype for a preclinical animal model, we generated a mouse with neuroretinal-specific loss of the von Hippel Lindau tumor suppressor protein, a protein that targets HIF1α for ubiquitination. We found that the neuroretinal cells in these mice overexpressed HIF1α and developed severe, irreversible ischemic retinopathy that has features of human PDR. Rapid progression of retinopathy in these mutant mice should facilitate the evaluation of therapeutic agents for ischemic and inflammatory blinding disorders. In addition, this model system can be used to manipulate the modulation of the hypoxia signaling pathways, for the treatment of non-ocular ischemic and inflammatory disorders. PMID:27195131

  17. Nuclear Morphometry in Ductal Breast Carcinoma with Correlation to Cell Proliferative Activity and Prognosis

    International Nuclear Information System (INIS)

    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

  18. Antibody response and antibody affinity maturation in cats with experimental proliferative immune complex glomerulonephritis.

    Science.gov (United States)

    Bishop, S A; Bailey, M; Lucke, V M; Stokes, C R

    1992-07-01

    An experimental model of proliferative glomerulonephritis (GN) in the cat, which closely resembles human proliferative forms of GN, has been used to study the role of antibody and antibody affinity in the development of immune complex-mediated renal disease. The serum IgG and IgM antibody response to antigen, average antibody affinity (avidity) and affinity heterogeneity of the IgG and IgM populations was assessed at varying times after commencement of chronic immunization with the antigen, human serum albumin (HSA), by enzyme immunoassay. Cats could be classified according to whether they were "low", "intermediate" or "high" IgG responders, by quantification of serum IgG values. Cats with the lowest serum IgG values failed to develop glomerulonephritis. However, there was no relationship between actual IgG values and the severity of the induced disease. In contrast to IgG, there was no division of cats into low or high IgM anti-HSA responders. Again, cats with the lowest IgM values failed to develop GN, but, more interestingly, a late, marked increase in serum IgM anti-HSA occurred only in cats that developed clinical signs of GN (anterior uveitis and nephrotic syndrome). Maturation of average, functional IgG affinity (avidity) for HSA following chronic immunization was clearly demonstrated for all cats. At the end of the experiment, all cats had IgG of high affinity for HSA and the average affinity heterogeneity of the IgG populations was less than in measurements taken earlier. Values of IgG affinity at the end of the experiment were very similar both in cats which developed GN and in those which remained clinically, biochemically and pathologically normal. In contrast to IgG antibody, some cats developed IgM of increased affinity, whilst others produced antibody of reduced affinity, following chronic immunization. There was no correlation between the development of disease and the production of either low or high affinity IgM antibody. Data indicated that an

  19. [A familial case of proliferative diabetic retinopathy associated with a mutation in the mitochondrial gene].

    Science.gov (United States)

    Kuze, M; Arima, M; Saso, M; Uji, Y

    1998-11-01

    We report a 39-year-old male patient with proliferative diabetic retinopathy associated with a mutation in the mitochondrial DNA and with his family. The patient was referred for fundus examination in 1993. He had been diagnosed as having diabetes mellitus 15 years before but his diabetic control was not good. He was thin and short and presented with bilateral proliferative diabetic retinopathy. When he received pan retinal photocoagulation, an exudative retinal detachment was found in his left eye, but it disappeared spontaneously. The patient's history included sensorineural deafness and autonomic nerve system disorder. Mitochondrial analysis obtained from blood showed mutation of adenine to guanine at mitochondrial DNA 3243. Generally speaking, mitochondrial disorders often include pigmentary degeneration. For this reason diabetic patients with mitochondrial disorders rarely suffer proliferative diabetic retinopathy. In this case, the retinitis pigmentosa was not so severe as to cause the proliferative change, so that it was probably derived from heteroplasmy. PMID:9852718

  20. PUF-8, a Pumilio Homolog, Inhibits the Proliferative Fate in the Caenorhabditis elegans Germline

    OpenAIRE

    Racher, Hilary; Hansen, Dave

    2012-01-01

    Stem cell populations are maintained by keeping a balance between self-renewal (proliferation) and differentiation of dividing stem cells. Within the Caenorhabditis elegans germline, the key regulator maintaining this balance is the canonical Notch signaling pathway, with GLP-1/Notch activity promoting the proliferative fate. We identified the Pumilio homolog, PUF-8, as an inhibitor of the proliferative fate of stem cells in the C. elegans germline. puf-8(0) strongly enhances overproliferatio...

  1. Nuclear tomography of rheumatic arthropathy. Imaging of normal and of proliferatively swollen synovial membrane

    Energy Technology Data Exchange (ETDEWEB)

    Reiser, M.; Lehner, K.; Rupp, N.; Zacher, J.; Heizer, K.; Weigert, F.

    1986-09-01

    An indication of synovectomy has to be based on accurate diagnostic data including differentiation between exsudative and proliferative forms of early-stage synovitis, and discrimination of hydrarthrosis from fibrinous coats and from proliferative swelling of capsula articularis. The study in hand collects MR tomographic data for description of chronic polyarthritis in order to ascertain whether MR imaging techniques yield better data on the state of the soft tissues of bone joints. (orig./SHA).

  2. Nuclear tomography of rheumatic arthropathy. Imaging of normal and of proliferatively swollen synovial membrane

    International Nuclear Information System (INIS)

    An indication of synovectomy has to be based on accurate diagnostic data including differentiation between exsudative and proliferative forms of early-stage synovitis, and discrimination of hydrarthrosis from fibrinous coats and from proliferative swelling of capsula articularis. The study in hand collects MR tomographic data for description of chronic polyarthritis in order to ascertain whether MR imaging techniques yield better data on the state of the soft tissues of bone joints. (orig./SHA)

  3. Alpha-lipoic acid in non-proliferative diabetic retinopathy treatment

    OpenAIRE

    Tat'yana Yul'evna Demidova; Yuliya Aleksandrovna Trakhtenberg

    2011-01-01

    Aim. The aim of this study is to assess the therapeutic efficacy of alpha-lipoic acid in patients with type 2 diabetes mellitus (DM) and non-proliferative diabetic retinopathy. Materials and methods. 47 patients with mild to moderate non-proliferative diabetic retinopathy were included in this trial. Dynamics of ophthalmologic parameters were assessed by means of stereoscopic photography of ocular fundus. Patients were examined every 6 months in order to register new cases of clin...

  4. Intravitreal bevacizumab treatment for retinal neovascularization and vitreous hemorrhage in proliferative diabetic retinopathy

    OpenAIRE

    Ashraf M El-Batarny

    2007-01-01

    Purpose: To report the short term anatomical and visual acuity response after intravitreal injection of bevacizumab in patients with proliferative diabetic retinopathy. Methods: Ten eyes having proliferative diabetic retinopathy were treated with at least one intravitreal injection of bevacizumab, 1.25 mg in 0.05 mL. Patients underwent complete ophthalmologic evaluation at baseline and follow up visits including Snellen’s best corrected visual acuity (BCVA), fundus biomicroscopy and fluoresce...

  5. Peripheral retinal ablation in the treatment of proliferative diabetic retinopathy during pregnancy.

    OpenAIRE

    Hercules, B L; Wozencroft, M; Gayed, I I; Jeacock, J

    1980-01-01

    The course of proliferative diabetic retinopathy involving the optic disc was followed, and the response to peripheral retinal photocoagulation monitored by argon laser in 11 patients during and after 13 pregnancies. Traditional obstetric practice assumes that pregnancy is a stimulus to irreversible progression of proliferative diabetic retinopathy, and that timely abortion and sterilisation are essential in order to achieve control of the neovascular process. Extensive photocoagulation will ...

  6. Postvitrectomy diabetic vitreous hemorrhage in proliferative diabetic retinopathy

    Directory of Open Access Journals (Sweden)

    Lei Shi

    2012-01-01

    Full Text Available Background: To investigate the reasons for postvitrectomy diabetic vitreous hemorrhage (PDVH, and to analyze the time of PDVH onset, the treatment of PDVH, the visual outcome of the treatment, and factors that affect visual acuity after treatment. Materials and Methods: Overall, 292 eyes from 236 patients with proliferative diabetic retinopathy (PDR underwent vitrectomy from 2006 to 2010. Fifty eyes out of 43 patients had severe postoperative vitreous hemorrhage. The average follow-up duration was 6.8 ± 3.8 months (range, 2-12 months. Results: Recurrent vitreous hemorrhage (VH after primary vitrectomy occurred in 40 eyes (80% with an average time of VH onset of 62.5 ± 32.8 days (range, 3-170 days. VH occurred after silicone oil removal occurred in 10 eyes (20%, with an average time of VH onset of 27.4 ± 20.3 days (range, 1-60 days. The reasons for PDVH included chronic errhysis from retinal neovessels (47.1% of the eyes, residual fibrous vascular membrane (12.8% of the eyes, fibrovascular ingrowth at sclerotomy sites (4.3% of the eyes, iris neovessels and neovascular glaucoma (4.3% of the eyes, retinal vein occlusion (2.8% of the eyes, retinal tears (8.1% of the eyes, retinotomy (1.4% of the eyes, epichoroidal bleeding (1.4% of the eyes, polycythemia rubra vera (1.4% of the eyes, hypoperfusional retinopathy (4.3% of the eyes, and unknown reasons (12.8% of the eyes. Visual acuity increased in 43 eyes (86% after surgical or nonsurgical treatment. The improvement in visual acuity after treatment was not affected by age, sex, duration of diabetes, time of PDVH onset, frequency of surgery, or treatment methods. Conclusion: Postvitrectomy diabetic vitreous hemorrhage commonly occurs two months after vitrectomy. Residual epiretinal neovascularization is the most common cause of PDVH. Active surgical or nonsurgical treatment for severe vitreous hemorrhage can obviously improve the patients′ visual prognosis.

  7. Proliferative activity in oral pyogenic granuloma: A comparative immunohistochemical study

    Directory of Open Access Journals (Sweden)

    Rezvani Gita

    2010-07-01

    Full Text Available Context: Pyogenic granuloma (PG is one of the most common reactive vascular lesions in the oral mucosa, which has been divided into the lobular capillary hemangioma (LCH and the non lobular type (non-LCH as two distinct entities, on the basis of some investigations. Aims: This study aims to compare the proliferative and angiogenic activity of two histological types of PG to determine whether they have two distinct types of biological behavior. Settings and Design: In this retrospective cross-sectional study, immunostaining was performed on 10 cases of each type of PG. Materials and Methods: About 4μm sections were cut from formalin-fixed paraffin-embedded blocks and each specimen was stained with both anti-CD31 and anti-Ki-67 antibodies simultaneously. Labeling index (LI was determined for both types by counting Ki-67 and CD31 positive cells separately and simultaneously in 1000 stromal and luminal cells. Micro vessel count (MVC, the mean number of micro vessels in five areas at Χ200 magnification, was also determined for both groups. Statistical Analysis: The results were statistically compared using the Mann-Whitney U-test. Results: Ki-67 LI in LCH (5.4 ± 2.4 was higher than non-LCH (3.9 ± 3.9. The percentage of CD31 positive cells in LCH (28.5 ± 22 was lower than non-LCH (37.1 ± 20.8 and simultaneously immunostaining for both markers in LCH type (2.4 ± 2.1 was higher than non-LCH (1.2 ± 1. The MVC was approximately 77.35 ± 34.6 and 82.6 ± 42.7 in the lobular areas of LCH and central areas of non-LCH PG, respectively. These differences were not statistically significant. Conclusions: These results demonstrate a higher proliferation activity in endothelial cells of LCH PG than in non-LCH.

  8. Remission of proteinuria indicates good prognosis in patients with diffuse proliferative lupus nephritis.

    Science.gov (United States)

    Koo, H S; Kim, S; Chin, H J

    2016-01-01

    Proteinuria is a well-known risk factor for the progression of renal dysfunction in chronic kidney disease; however, its importance for estimating the prognosis of lupus nephritis requires verification. Korean adult patients with renal biopsy-diagnosed diffuse proliferative lupus nephritis who had undergone three or more consecutive urine protein to creatinine ratio or urine dipstick tests within six months after renal biopsy were enrolled. The cumulative risks, predictors, and outcomes of proteinuric remission and flare were evaluated. This study included 26 men and 167 women with a mean age at renal biopsy of 31.2 ± 9.8 years. Eighty-two (42.5%) patients experienced proteinuric remission during the follow-up period. During a mean follow-up of 157.9 ± 69.5 months, among patients who achieved proteinuric remission, one died, one developed end-stage renal disease (ESRD), and two had composite outcomes; among patients without remission, nine died, 24 developed ESRD, and 30 had composite outcomes. Patients who achieved proteinuric remission had a 0.089-fold risk (95% CI: 0.011-0.736) of mortality, 0.110-fold risk (95% CI: 0.013-0.904) of incident ESRD, and 0.210-fold risk (95% CI: 0.048-0.920) of a composite outcome compared to patients without remission. Among the 82 patients who achieved proteinuric remission, 59 (72.0%) experienced at least one proteinuria flare; however, relapse did not correlate with the incidence of outcomes. In conclusion, proteinuric remission is an independent predictive prognostic marker of good renal survival and mortality, regardless of the interval from biopsy to remission, recurrence of proteinuria after remission, renal function status at remission, or hematuria remission. PMID:26159540

  9. Proliferative responses to myocardial remodeling in the developing heart

    Czech Academy of Sciences Publication Activity Database

    Sedmera, David; Kučera, P.; Kolář, František; Thompson, R.P.

    1. Malden: Blackwell Publishing, 2005 - (Artman, M.; Benson, W.; Srivastava, D.; Nakazawa, M.), s. 47-51 ISBN 1-4051-3128-4 R&D Projects: GA MŠk(CZ) 1M0510 Grant ostatní: NIH(US) HL50582; SC COBRE in Cardiovascular Diseases(US) RR 16434-01; MOD Basil O'Connor(US) 5-FY03-118 Institutional research plan: CEZ:AV0Z50110509 Keywords : cardiomyocyte * hyperplasia * development Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

  10. DISEASES

    DEFF Research Database (Denmark)

    Pletscher-Frankild, Sune; Pallejà, Albert; Tsafou, Kalliopi;

    2015-01-01

    Text mining is a flexible technology that can be applied to numerous different tasks in biology and medicine. We present a system for extracting disease-gene associations from biomedical abstracts. The system consists of a highly efficient dictionary-based tagger for named entity recognition of...... human genes and diseases, which we combine with a scoring scheme that takes into account co-occurrences both within and between sentences. We show that this approach is able to extract half of all manually curated associations with a false positive rate of only 0.16%. Nonetheless, text mining should not...... stand alone, but be combined with other types of evidence. For this reason, we have developed the DISEASES resource, which integrates the results from text mining with manually curated disease-gene associations, cancer mutation data, and genome-wide association studies from existing databases. The...

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

    International Nuclear Information System (INIS)

    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

  12. APOPTOTIC AND PROLIFERATIVE ACTIVITY IN OVARIAN BENIGN,BORDERLINE AND MALIGNANT TUMORS

    Institute of Scientific and Technical Information of China (English)

    刘爱军; 陈乐真; 颜婉嫦; 邱玮璇; 赵昀; 张雅贤

    2002-01-01

    Objective.To determine the apoptotic and proliferative activities in various ovarian epithelial tumors.Methods.Formalin fixed,paraffin embedded tissues of 86 ovarian epithelial tumors,including 52 adenocarcinomas,23 borderline tumors and 11 cystadenomas,were retrieved.Apoptotic (AI) and proliferative (PI) index were estimated using the monoclonal antibodies: M30,Ki 67 and Ki S1 in these tumors.Quantitative assessment of AI and PI was estimated by calculating the percentage of positive cells among no less than 1000 tumor cells.Results.Statistically significant difference in AI was found between benign and borderline tumors or carcinomas (P=0.028,0.001,respectively).Significant differences in PI,as assessed by both Ki 67 and topo IIα,were demonstrated between carcinomas and benign or borderline tumors (both P< 0.001).Benign tumors had both low PI and AI; borderline tumors had lower PI but higher AI,while adenocarcinomas had both high proliferative and high apoptotic rates.Among borderline tumors,serous tumors had significantly lower AI and higher PI than mucinous ones.Conclusions.The results suggest that apoptotic and proliferative activities play important roles in the pathogenesis and development of ovarian borderline and malignant tumors.The high apoptotic rate in borderline tumor may explain its relatively indolent behavior while the high proliferative rate in carcinomas tends to explain its aggressive behavior.

  13. Trichostatin A Inhibits Retinal Pigmented Epithelium Activation in an In Vitro Model of Proliferative Vitreoretinopathy

    Science.gov (United States)

    Greene, Whitney A.; Burke, Teresa A.; Wang, Heuy-Ching

    2016-01-01

    Abstract Purpose: Proliferative vitreoretinopathy (PVR) is a blinding disorder that develops after a retinal tear or detachment. Activation of the retinal pigmented epithelium (RPE) is implicated in PVR; however, the mechanisms leading to enhanced RPE proliferation, migration, and contraction remain largely unknown. This study utilized an in vitro model of PVR to investigate the role of acetylation in RPE activation and its contribution to the progression of this disease. Methods: ARPE-19 cells, primary cultures of porcine RPE, and induced pluripotent stem cell-derived RPE (iPS-RPE) were utilized for cellular and molecular analyses. Cells treated with transforming growth factor beta 2 (TGFβ2; 10 ng/mL) alone or in the presence of the broad-spectrum histone deacetylase (HDAC) inhibitor, trichostatin A (TSA; 0.1 μM), were assessed for contraction and migration through collagen contraction and scratch assays, respectively. Western blotting and immunofluorescence analysis were performed to assess α-smooth muscle actin (α-SMA) and β-catenin expression after TGFβ2 treatment alone or in combination with TSA. Results: TGFβ2 significantly increased RPE cell contraction in collagen matrix and this effect was inhibited in the presence of TSA (0.1 μM). In agreement with these data, immunofluorescence analysis of TSA-treated iPS-RPE wounded monolayers revealed decreased α-SMA as compared with control. Scratch assays to assess wound healing revealed TSA inhibited TGFβ2-mediated iPS-RPE cell migration. Conclusions: Our findings indicate a role of acetylation in RPE activation. Specifically, the HDAC inhibitor TSA decreased RPE cell proliferation and TGFβ2-mediated cell contraction and migration. Further investigation of pharmacological compounds that modulate acetylation may hold promise as therapeutic agents for PVR. PMID:27494828

  14. Molecular and hormonal regulation of angiogenesis in proliferative endometrium

    OpenAIRE

    Yousef Rezaei Chianeh; Pragna Rao

    2014-01-01

    Angiogenesis is a hallmark of wound healing, the menstrual cycle, cancer, and various ischemic and inflammatory diseases. A rich variety of pro and anti-angiogenic molecules have already been identified. Vascular endothelial growth factor (VEGF) is an interesting inducer of angiogenesis and lymphangiogenesis, because it is a highly specific mitogen for endothelial cells. Signal transduction involves binding to tyrosine kinase receptors and results in endothelial cell proliferation, migration,...

  15. PUF-8, a Pumilio homolog, inhibits the proliferative fate in the Caenorhabditis elegans germline.

    Science.gov (United States)

    Racher, Hilary; Hansen, Dave

    2012-10-01

    Stem cell populations are maintained by keeping a balance between self-renewal (proliferation) and differentiation of dividing stem cells. Within the Caenorhabditis elegans germline, the key regulator maintaining this balance is the canonical Notch signaling pathway, with GLP-1/Notch activity promoting the proliferative fate. We identified the Pumilio homolog, PUF-8, as an inhibitor of the proliferative fate of stem cells in the C. elegans germline. puf-8(0) strongly enhances overproliferation of glp-1(gf) mutants and partially suppresses underproliferation of a weak glp-1(lf) mutant. The germline tumor that is formed in a puf-8(0); glp-1(gf) double mutant is due to a failure of germ cells to enter meiotic prophase. puf-8 likely inhibits the proliferative fate through negatively regulating GLP-1/Notch signaling or by functioning parallel to it. PMID:23050230

  16. Compression Myelopathy due to Proliferative Changes around C2 Pars Defects without Instability

    Science.gov (United States)

    Kimura, Tetsuya; Tezuka, Fumitake; Abe, Mitsunobu; Yamashita, Kazuta; Takata, Yoichiro; Higashino, Kosaku; Sairyo, Koichi

    2016-01-01

    We report a case with compression myelopathy due to proliferative changes around the C2 pars defects without instability. A 69-year-old man presented with progressive clumsy hands and spastic gait. Plain radiographs showed bilateral spondylolysis (pars defects) at C2 and fusion between C2 and C3 spinous processes. Dynamic views revealed mobility through the pars defects, but there was no apparent instability. Computed tomography showed proliferative changes at the pars defects, which protruded into spinal canal. On magnetic resonance imaging, the spinal cord was compressed and intramedullary high signal change was found. A diagnosis of compression myelopathy due to proliferative changes around the C2 pars defects was made. We performed posterior decompression. Postoperatively, symptoms have been alleviated and images revealed sufficient decompression and no apparent instability. In patients with the cervical spondylolysis, myelopathy caused by instability or slippage have been periodically reported. The present case involving C2 spondylolysis is extremely rare. PMID:27340539

  17. Compression Myelopathy due to Proliferative Changes around C2 Pars Defects without Instability.

    Science.gov (United States)

    Kimura, Tetsuya; Sakai, Toshinori; Tezuka, Fumitake; Abe, Mitsunobu; Yamashita, Kazuta; Takata, Yoichiro; Higashino, Kosaku; Sairyo, Koichi

    2016-06-01

    We report a case with compression myelopathy due to proliferative changes around the C2 pars defects without instability. A 69-year-old man presented with progressive clumsy hands and spastic gait. Plain radiographs showed bilateral spondylolysis (pars defects) at C2 and fusion between C2 and C3 spinous processes. Dynamic views revealed mobility through the pars defects, but there was no apparent instability. Computed tomography showed proliferative changes at the pars defects, which protruded into spinal canal. On magnetic resonance imaging, the spinal cord was compressed and intramedullary high signal change was found. A diagnosis of compression myelopathy due to proliferative changes around the C2 pars defects was made. We performed posterior decompression. Postoperatively, symptoms have been alleviated and images revealed sufficient decompression and no apparent instability. In patients with the cervical spondylolysis, myelopathy caused by instability or slippage have been periodically reported. The present case involving C2 spondylolysis is extremely rare. PMID:27340539

  18. 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.

  19. Tristetraprolin mediates the anti-proliferative effects of metformin in breast cancer cells

    OpenAIRE

    Pandiri, Indira; Chen, Yingqing; Joe, Yeonsoo; Kim, Hyo Jeong; Park, Jeongmin; Chung, Hun Taeg; Park, Jeong Woo

    2016-01-01

    Metformin, which is a drug commonly prescribed to treat type 2 diabetes, has anti-proliferative effects in cancer cells; however, the molecular mechanisms underlying this effect remain largely unknown. The aim is to investigate the role of tristetraprolin (TTP), an AU-rich element-binding protein, in anti-proliferative effects of metformin in cancer cells. p53 wild-type and p53 mutant breast cancer cells were treated with metformin, and expression of TTP and c-Myc was analyzed by semi-quantit...

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

    OpenAIRE

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

    2014-01-01

    Aim: This work has been designed to evaluate the anti-proliferative and cytostatic effects of Citrus sinensis (orange) fruit juice on rapidly proliferating cells. Materials and Methods: 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. Result: The result showed that when compared with the control, methotrexate, the standard drug showed a significant (P < 0.001) anti-proliferative effect throughout the experi...

  1. Molecular and hormonal regulation of angiogenesis in proliferative endometrium

    Directory of Open Access Journals (Sweden)

    Yousef Rezaei Chianeh

    2014-02-01

    Full Text Available Angiogenesis is a hallmark of wound healing, the menstrual cycle, cancer, and various ischemic and inflammatory diseases. A rich variety of pro and anti-angiogenic molecules have already been identified. Vascular endothelial growth factor (VEGF is an interesting inducer of angiogenesis and lymphangiogenesis, because it is a highly specific mitogen for endothelial cells. Signal transduction involves binding to tyrosine kinase receptors and results in endothelial cell proliferation, migration, and new vessel formation. In this article, the role of VEGF and other growth factors in the pathology of dysfunctional uterine bleeding is reviewed. We also discuss the role of VEGF expression and interaction with extracellular matrix that lead to possible inhibition or stimulation of Angiogenic factor on endometrium of dysfunctional uterine bleeding patients. [Int J Res Med Sci 2014; 2(1.000: 1-9

  2. Reconciling Faith and Fact: Pro-life Women Discuss Media, Science and the Abortion Debate.

    Science.gov (United States)

    Press, Andrea L.; Cole, Elizabeth R.

    1995-01-01

    Finds that pro-life women actively searched for authorities and authoritative information that were not "corrupted" by the values of secular society. Finds that, paradoxically, they drew on secular forms of argument, claiming scientific authenticity for their own sources, and that their selective viewing habits resulted in the construction of an…

  3. Sustained Inhibition of Proliferative Response After Transient FGF Stimulation Is Mediated by Interleukin 1 Signaling.

    Science.gov (United States)

    Poole, Ashleigh; Kacer, Doreen; Cooper, Emily; Tarantini, Francesca; Prudovsky, Igor

    2016-03-01

    Transient FGF stimulation of various cell types results in FGF memory--a sustained blockage of efficient proliferative response to FGF and other growth factors. FGF memory establishment requires HDAC activity, indicating its epigenetic character. FGF treatment stimulates proinflammatory NFκB signaling, which is also critical for FGF memory formation. The search for FGF-induced mediators of FGF memory revealed that FGF stimulates HDAC-dependent expression of the inflammatory cytokine IL1α. Similarly to FGF, transient cell treatment with recombinant IL1α inhibits the proliferative response to further FGF and EGF stimulation, but does not prevent FGF receptor-mediated signaling. Interestingly, like cells pretreated with FGF1, cells pretreated with IL1α exhibit enhanced restructuring of actin cytoskeleton and increased migration in response to FGF stimulation. IRAP, a specific inhibitor of IL 1 receptor, and a neutralizing anti-IL1α antibody prevent the formation of FGF memory and rescue an efficient proliferative response to FGF restimulation. A similar effect results following treatment with the anti-inflammatory agents aspirin and dexamethasone. Thus, FGF memory is mediated by proinflammatory IL1 signaling. It may play a role in the limitation of proliferative response to tissue damage and prevention of wound-induced hyperplasia. PMID:26218437

  4. Influence of pro-angiogenic cytokines on proliferative activity and survival of endothelial cells

    Directory of Open Access Journals (Sweden)

    Solyanik G. I.

    2010-04-01

    Full Text Available Aim. Tumor angiogenesis in contrast to physiological one is characterized by high level of malignant cell production of proangiogenic cytokines, which have different influence on functional activity of endothelial cells. The goal of the study – to carry out a comparative analysis of the influence of a vascular endothelial growth factor (VEGF and an epidermal growth factor (EGF on proliferative activity and survival of endothelial cells upon their confluent and exponential growth. Methods. The proliferative activity of endothelial cells was determined by MTT-test and their viability was detected by the trypane blue exclusion test. Results. It was shown that EGF (irrespectively of the level of serum factors in concentrations higher than 10 ng/ml activated the proliferative activity of confluent endotheliocytes in a concentration-dependent manner by 18–36 % (ð < 0.05 as compared to the control, while this cytokine didn’t affect the endothelial cells in the exponential growth phase. VEGF in wide concentration range didn’t display the mitogenic effect on endotheliocytes in both confluent and exponential growth phases. Furthermore, VEGF in concentrations higher than 100 ng/ml inhibited proliferative activity of confluent endothelial cells by 12 % (ð < 0.05. In case of deficiency of nutrients, EGF and VEGF promoted the survival of endothelial cells, considerably decreasing their death. Conclusions. EGF, in contrast to VEGF, stimulates proliferation and survival of the endothelial cells, whereas VEGF has significant influence only on the survival of the cells

  5. Reactivity in ELISA with DNA-loaded nucleosomes in patients with proliferative lupus nephritis

    NARCIS (Netherlands)

    Dieker, J.W.; Schlumberger, W.; McHugh, N.; Hamann, P.; Vlag, J. van der; Berden, J.H.M.

    2015-01-01

    Autoantibodies against nucleosomes are considered a hallmark of systemic lupus erythematosus (SLE). We compared in patients with proliferative lupus nephritis the diagnostic usefulness of a dsDNA-loaded nucleosome ELISA (anti-dsDNA-NcX) with ELISAs in which dsDNA or nucleosomes alone were coated. Fi

  6. Specific detection of Lawsonia intracellularis in porcine proliferative enteropathy inferred from fluorescent rRNA in situ hybridization

    DEFF Research Database (Denmark)

    Boye, Mette; Jensen, Tim Kåre; Møller, Kristian; Leser, T.D.; Jorsal, Sven Erik Lind

    1998-01-01

    probe was determined by simultaneous comparison with indirect immunofluorescence assay for detection of L. intracellularis in formalin-fixed tissue samples from 15 pigs affected by porcine proliferative enteropathy. We used 10 tissue samples from pigs without proliferative mucosal changes as negative...

  7. TU-F-12A-02: Quantitative Characterization of Normal Bone Marrow Proliferative Activity with FLT PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Weisse, N; Jeraj, R [Department of Medical Physics, University of Wisconsin, Madison, WI (United States)

    2014-06-15

    Purpose: [F-18]FLT PET is a tool for assessing health of bone marrow by evaluating its proliferative activity. This study establishes a baseline quantitative characterization of healthy marrow proliferation to aid in diagnosis of hematological disease. Methods: 31 patients (20 male, 11 female, 41–76 years) being treated for solid cancers with no history of hematological disease, osseous metastatic disease, or radiation therapy received pre-treatment FLT PET/CT scans. Total bone marrow was isolated from whole body FLT PET images by manually removing organs and applying a standardize uptake value (SUV) threshold of 1.0. Because adult marrow is concentrated in the axial skeleton, quantitative total bone marrow analysis (QTBMA) was used to isolate marrow in the lumbar spine, thoracic spine, sacrum, and pelvis for analysis. SUVmean, SUVmax, and SUVCV were used to quantify bone marrow proliferation. Correlations were explored between SUV and patient characteristics including age, weight, height, and BMI using the Spearman coefficient (ρ). Results: The population-averaged whole-skeleton SUVmean, SUVmax, and SUVCV were 3.0±0.6, 18.4±5.7, and 0.6±0.1, respectively. Uptake values in the axial skeleton were similar to the whole-skeleton demonstrated by SUVmean in the thoracic spine (3.6±0.6), lumbar spine (3.3±0.5), sacrum (3.0±0.6), and pelvis regions (2.8±0.5). Whole-skeleton SUVmax correlated with patient weight (ρ=0.47, p<0.01) and BMI (ρ=0.60, p<0.01), suggesting marrow activity is related to the body's burden. SUV measures in the thoracic spine, lumbar spine, sacrum, and pelvis were negatively correlated with age (ρ:−0.41 to −0.46, p≤0.02). These negative correlations reflect the fact that active marrow in the adult skeleton is localized in the axial skeleton and decreases with age. Conclusions: Normal bone marrow characterizations were determined using FLT

  8. TU-F-12A-02: Quantitative Characterization of Normal Bone Marrow Proliferative Activity with FLT PET/CT

    International Nuclear Information System (INIS)

    Purpose: [F-18]FLT PET is a tool for assessing health of bone marrow by evaluating its proliferative activity. This study establishes a baseline quantitative characterization of healthy marrow proliferation to aid in diagnosis of hematological disease. Methods: 31 patients (20 male, 11 female, 41–76 years) being treated for solid cancers with no history of hematological disease, osseous metastatic disease, or radiation therapy received pre-treatment FLT PET/CT scans. Total bone marrow was isolated from whole body FLT PET images by manually removing organs and applying a standardize uptake value (SUV) threshold of 1.0. Because adult marrow is concentrated in the axial skeleton, quantitative total bone marrow analysis (QTBMA) was used to isolate marrow in the lumbar spine, thoracic spine, sacrum, and pelvis for analysis. SUVmean, SUVmax, and SUVCV were used to quantify bone marrow proliferation. Correlations were explored between SUV and patient characteristics including age, weight, height, and BMI using the Spearman coefficient (ρ). Results: The population-averaged whole-skeleton SUVmean, SUVmax, and SUVCV were 3.0±0.6, 18.4±5.7, and 0.6±0.1, respectively. Uptake values in the axial skeleton were similar to the whole-skeleton demonstrated by SUVmean in the thoracic spine (3.6±0.6), lumbar spine (3.3±0.5), sacrum (3.0±0.6), and pelvis regions (2.8±0.5). Whole-skeleton SUVmax correlated with patient weight (ρ=0.47, p<0.01) and BMI (ρ=0.60, p<0.01), suggesting marrow activity is related to the body's burden. SUV measures in the thoracic spine, lumbar spine, sacrum, and pelvis were negatively correlated with age (ρ:−0.41 to −0.46, p≤0.02). These negative correlations reflect the fact that active marrow in the adult skeleton is localized in the axial skeleton and decreases with age. Conclusions: Normal bone marrow characterizations were determined using FLT

  9. Effects of progestins of human proliferative endometrium: an in vitro model of potential clinical relevance.

    Science.gov (United States)

    Illouz, Séverine; Dales, Jean-Philippe; Sferlazzo, Karine; Garcia, Stéphane; Carpentier-Meunier, Séverine; Boubli, Léon; Lavaut, Marie-Noelle; Charpin, Colette

    2003-10-01

    Endometrium biopsy is a useful indicator of endometrium proliferation and is clinically relevant to diagnose cell proliferation and to evaluate response to progestin treatment and to monitor hormone replacement therapy. The aim of our study was to investigate the in vitro effects of progesterone and synthetic progestins on endometrium explants with a particular focus on estradiol receptor (ER) and progesterone receptor (PR) expression which reflects through cell secretion the hormone treatment efficiency. Most widely used progestagens belonging to three distinctive groups were investigated, i.e, medroxyprogesterone acetate (MPA), norethindrone acetate (NOR) and nomegestrol acetate (TX) which are respectively pregnane, 19-nortestosterone and norpregnane derivatives. We used organ culture from human proliferative endometrium, in which tissue integrity, particularly gland/stroma relationships are preserved. Progestins induce epithelial cell secretion and most effects were observed at the highest concentration tested (10(-7) M) and by TX and MPA on homogeneous and on heterogeneous (including also secretory glands) proliferative endometrium respectively. In these conditions, ER as well as PR expression were decreased on both glandular and stromal cells. In contrast, progesterone at 10(-7) M significantly decreased only PR, in glands and in stroma of homogeneous proliferative endometrium, and just in stroma of heterogeneous endometrium. NOR exhibited less effects. At lower concentrations (10(-8) M, 10(-9) M), significantly less effects were observed by synthetic progestins on proliferative endometrium. The experiments show that the different types of progestins do not exhibit in vitro similar effects. Since progestins variably act on proliferative endometrium, the exposure of endometrium explants to progestins may be a useful tool to predict clinical response to hormone therapy (individual "hormonogram") and to monitor endometrium proliferation. PMID:12964029

  10. Ocular surface changes in type II diabetic patients with proliferative diabetic retinopathy

    Institute of Scientific and Technical Information of China (English)

    Yan; Gao; Yan; Zhang; Yu-Sha; Ru; Xiao-Wu; Wang; Ji-Zhong; Yang; Chun-Hui; Li; Hong-Xing; Wang; Xiao-Rong; Li; Bing; Li

    2015-01-01

    AIM: To detect and analyze the changes on ocular surface and tear function in type II diabetic patients with proliferative diabetic retinopathy(PDR), an advanced stage of diabetic retinopathy(DR), using conventional ophthalmic tests and the high-resolution laser scanning confocal microscopy.METHODS: Fifty-eight patients with type II diabetes were selected. Based on the diagnostic criteria and stage classification of DR, the patients were divided into the non-DR(NDR) group and the PDR group. Thirty-six patients with cataract but no other ocular and systemic disease were included as non-diabetic controls. All the patients were subjected to the conventional clinical tests of corneal sensitivity, Schirmer I test, and corneal fluorescein staining. The non-invasive tear film break-up time(NIBUT) and tear interferometry were conducted by a Tearscope Plus. The morphology of corneal epithelia and nerve fibers was examined using the high-resolution confocal microscopy.RESULTS: The NDR group exhibited significantly declined corneal sensitivity and Schirmer I test value, as compared to the non-diabetic controls(P <0.001). The PDR group showed significantly reduced corneal sensitivity, Schirmer I test value, and NIBUT in comparison to the non-diabetic controls(P <0.001).Corneal fluorescein staining revealed the progressively injured corneal epithelia in the PDR patients. Moreover,significant decrease in the corneal epithelial density andmorphological abnormalities in the corneal epithelia and nerve fibers were also observed in the PDR patients.CONCLUSION: Ocular surface changes, including blunted corneal sensitivity, reduced tear secretion, tear film dysfunction, progressive loss of corneal epithelia and degeneration of nerve fibers, are common in type II diabetic patients, particularly in the diabetic patients with PDR. The corneal sensitivity, fluorescein staining scores,and the density of corneal epithelial cells and nerve fibers in the diabetic patients correlate with the

  11. Urinary protein markers predict the severity of renal histological lesions in children with mesangial proliferative glomerulonephritis

    Directory of Open Access Journals (Sweden)

    Li Yanhong

    2012-05-01

    Full Text Available Abstract Background Several renal histopathological features, including mesangial hypercellularity, glomerulosclerosis, tubular atrophy and interstitial fibrosis, are considered to be independent predictors of end-stage renal failure in patients with glomerular diseases. Mesangial proliferative glomerulonephritis (MesPGN is characterized by proliferations of mesangial cells with increase in mesangial matrix and/or deposits in mesangial region. The purpose of this study is to determine the association between urinary protein markers measured at the same time as renal biopsy and the severity of renal histological lesions in children with MesPGN, and to evaluate whether these markers could serve as predictors of severe renal histological lesions in this population. Methods Ninety-eight children with MesPGN (40 with IgA nephropathy, 37 with IgM nephropathy, and 21 with MesPGN without IgA/IgM deposition were enrolled. Urinary level of IgG, albumin, transferrin, α1-microglobulin, β2-microglobulin and N-acetyl-β-glucosaminidase from a morning sample before biopsy was measured. The scores of mesangial hypercellularity, glomerulosclerosis, and tubule-interstitial damage were used to semi-quantitatively evaluate renal histological lesions. Results The urine proteins, as independent factors associated with severe mesangial cellularity (> 5 mesangial cells/ mesangial area were transferrin, albumin, α1-microglobulin, IgG and 24-hour total protein, with severe glomerulosclerosis (≥ 10 % glomeruli showing segmental adhesions or sclerosis were transferrin and 24-hour total protein, and with severe tubule-interstitial damage (focal or diffuse tubular and interstitial lesions were transferrin and N-acetyl-β-glucosaminidase. Urinary transferrin achieved the area under-the-receiver-operating-characteristic curve (AUC of 0.86 and 0.82, respectively, for predicting severe mesangial cellularity and glomerulosclerosis. Urinary N

  12. Intracellular expression of the proliferative marker Ki-67 and viral proteins (NS3, NS5A and C in chronic, long lasting hepatitis C virus (HCV infection.

    Directory of Open Access Journals (Sweden)

    Karolina Olejniczak

    2008-01-01

    Full Text Available Hepatitis C virus (HCV continues to represent the main causative agent of the hepatitis, which leads to chronic transformation of the process in 60-80% individuals. It remains unclear how far cellular expression of HCV proteins in vivo may represent an index of progression of the disease and of proliferative activity in the liver in chronic hepatitis C. Aim of the studies included detection and subcellular localization of three HCV proteins (NS3, NS5A and C in liver biopsies from adults (n=19 with chronic, long lasting hepatitis C as related to hepatocyte proliferative activity. The immunocytochemical ABC (avidin biotin-peroxidase complex technique was applied, alone or associated with the ImmunoMax technique. Results of the immunocytochemical tests were compared to histological alterations in liver biopsies, proliferation index and with selected clinical data. A significantly higher expression of NS3 protein was noted, as compared to expressions of NS5A and C proteins. In all the patients, cytoplasmic localization of all proteins dominated over nuclear localization (p0.05. At the level of electron microscopy, protein localization in endoplasmic reticulum (ER membranes, mitochondria, perinuclear region and/or in hepatocyte cell nucleus was observed. No direct relationships could be demonstrated between expressions of HCV proteins and of Ki-67 antigen. No correlations could also be demonstrated between cellular expression of any HCV protein on one hand and grading or staging, alanine transaminase (ALT, serum level of HCV RNA or alpha-fetoprotein (AFP on the other. However, positive correlations were disclosed between proliferative activity of hepatocytes on one hand and patient's age, grading and staging on the other. Advanced hepatic fibrosis correlated also with serum levels of AFP. The studies were supplemented with data on subcellular localization of HCV proteins. Moreover, they indicated that in HCV infection grading and staging

  13. MR findings of bland and proliferative joint effusion in Knee joint

    International Nuclear Information System (INIS)

    To determine the MR imaging criteria by which bland and proliferative effusion of the knee may be differentiated. We retrospectively reviewed the MR images of 64 patients (65 cases), in whom T2-weighted sagittal scans revealed anteroposterior distension of the suprapatellar bursa of at least 0.5 cm. The patients were divided into two groups: bland effusion (n=3D36), and proliferative effusion ((n=3D29); pigmented villonodular synovitis (n=3D5), rheumatoid arthritis (n=3D6), septic arthritis (n=3D6), chronic synovitis (n=3D5), gouty arthritis (n=3D3), tuberculous arthritis (n=3D2), and lipoma arborescens (n=3D2)). All conditions were diagnosed on the basis of operative data or clinical criteria. The knee joint space was divided into four compartments: the suprapatellar pouch, central zone, posterior femoral recess, and subpopliteal recess, and the amount and distribution of effusion was then compared between the two groups. The ratios of the width and the length of the lateral recess of the suprapatellar bursa to those of its medial recess were determined, and the findings for the two groups were compared.Abnormality of the intracapular fat pads (prefemoral fat, Hoffa's fat, and quadriceps fat sign) as seen on sagittal scans, is a predictor proliferative effusion, and any such abnormality was evaluated. The synovium was classified as either thin or thick, and as having either a smooth or an irregular margin, as seen on Gadolinium-enhanced T1W1 images. As compared with bland effusion, proliferative effusion involved more prominent joint effusion in the suprapatellar pouch and posterior femoral recess, and in the suprapatellar bursa, the ratio of the width of the lateral recess to that of the medial recess was greater. When comparing the ratio of the length of the lateral recess to that of the medial recess, however, no significant statistical difference was noted. Sensitivity: specificity for proliferative effusion was 58%: 86% on coronal scan and 64%: 93% on axial

  14. In vitro anti-proliferative, anti-bacterial potential and induction of DNA strand break of partially purified Cuscuta reflexa Roxb.

    Directory of Open Access Journals (Sweden)

    Madhulika Bhagat

    2011-01-01

    Full Text Available Cuscuta reflexa is an important medicinal plant, mentioned in Ayurveda, an ancient Indian system of medicine. The plant is selected to evaluate the possibility for novel pharmaceuticals for anticancer and antibiotics drugs. Since most of these drugs had developed resisitance against currently used chemotherapeutics. This study describes the in vitro anti-proliferative, anti-bacterial and single stand DNA break of the holoprasitic plant Cuscuta reflexa. Bioassay-guided fractionation and partial purification of the plant were done and evaluated for antiproliferative activity against human cancer cell lines by SRB assay and single strand DNA break by comet assay. Further antibacterial activity was also performed by agar well diffusion assay. The alcoholic extract, chloroform fraction and partially purified ethylacetate-methanol (1:1 sub-fraction of C. reflexa showed anti-proliferative potential against IMR-32 and 502713 human cancer cell lines. Alcoholic extract exhibited anti-proliferative activity of 74% and 72%, chloroform fraction demonstrated 91% and 95% against neuroblastoma (IMR-32 and colon (502713 cancer cell lines at 100 μg/ml. Single strand DNA break of the chloroform fraction was also demonstrated using comet assay, indicating that possible mode of cell death may be apoptosis. Anti-microbial properties were evaluated against eight species of pathogenic and non-pathogenic microorganisms and maximum zone of inhibition for anti-bacterial activity was found against Staphylococcus aureus (22 mm by alcoholic extract, 21 mm by chloroform fraction and 12 mm by ethylacetate-methanol (1:1 sub-fraction. Minimum inhibitory concentration (MIC of the chloroform fraction was 1500 μg/ml for S. aureus. The plant was found to be equally effective against gram-positive and negative bacteria. Studies are well underway to isolate and identify active compounds from chloroform fraction and ethyl acetate:methanol (1:1 sub-fraction, which can be used as

  15. Dual blockade of the pro-inflammatory chemokine CCL2 and the homeostatic chemokine CXCL12 is as effective as high dose cyclophosphamide in murine proliferative lupus nephritis.

    Science.gov (United States)

    Devarapu, Satish Kumar; Kumar Vr, Santhosh; Rupanagudi, Khader Valli; Kulkarni, Onkar P; Eulberg, Dirk; Klussmann, Sven; Anders, Hans-Joachim

    2016-08-01

    Induction therapy of proliferative lupus nephritis still requires the use of unselective immunosuppressive drugs with significant toxicities. In search of more specific drugs with equal efficacy but fewer side effects we considered blocking pro-inflammatory chemokine monocyte chemoattractant protein-1 (MCP-1/CCL2) and homeostatic chemokine stromal cell-derived factor-1 (SDF-1/CXCL12), which both contribute to the onset and progression of proliferative lupus nephritis yet through different mechanisms. We hypothesized that dual antagonism could be as potent on lupus nephritis as the unselective immunosuppressant cyclophosphamide (CYC). We estimated serum levels of CCL2 and CXCL12 in patients with SLE (n=99) and compared the results with healthy individuals (n=21). In order to prove our hypothesis we used l-enantiomeric RNA Spiegelmer® chemokine antagonists, i.e. the CCL2-specific mNOX-E36 and the CXCL12-specific NOX-A12 to treat female MRL/lpr mice from week 12 to 20 of age with either anti-CXCL12 or anti-CCL2 alone or both. SLE patients showed elevated serum levels of CCL2 but not of CXCL12. Female MRL/lpr mice treated with dual blockade showed significantly more effective than either monotherapy in preventing proteinuria, immune complex glomerulonephritis, and renal excretory failure and the results are at par with CYC treatment. Dual blockade reduced leukocyte counts and renal IL-6, IL-12p40, CCL-5, CCL-2 and CCR-2 mRNA expression. Dual blockade of CCL2 and CXCL12 can be as potent as CYC to suppress the progression of proliferative lupus nephritis probably because the respective chemokine targets mediate different disease pathomechanisms, i.e. systemic autoimmunity and peripheral tissue inflammation. PMID:27392463

  16. A Cellular Automaton Model for Tumor Dormancy: Emergence of a Proliferative Switch

    CERN Document Server

    Chen, Duyu; Torquato, Salvatore

    2014-01-01

    Malignant cancers that lead to fatal outcomes for patients may remain dormant for very long periods of time. Although individual mechanisms such as cellular dormancy, angiogenic dormancy and immunosurveillance have been proposed, a comprehensive understanding of cancer dormancy and the "switch" from a dormant to a proliferative state still needs to be strengthened from both a basic and clinical point of view. Computational modeling enables one to explore a variety of scenarios for possible but realistic microscopic dormancy mechanisms and their predicted outcomes. The aim of this paper is to devise such a predictive computational model of dormancy with an emergent "switch" behavior. Specifically, we generalize a previous cellular automaton (CA) model for proliferative growth of solid tumor that now incorporates a variety of cell-level tumor-host interactions and different mechanisms for tumor dormancy, for example the effects of the immune system. Our new CA rules induce a natural "competition" between the tu...

  17. Analysis of p53 expression and proliferative assessment using PCNA in localized prostate carcinoma

    Directory of Open Access Journals (Sweden)

    Leite K.R.M.

    1999-01-01

    Full Text Available The surgical specimens from 51 men submitted to radical prostatectomy for localized prostate cancer were examined by immunohistochemistry using proliferation cell nuclear antigen (PCNA monoclonal antibody to evaluate the proliferative index (PI. The relationship between PI, biological variables and p53 protein expression was evaluated by immunohistochemistry. PI was low in invasive localized prostate carcinoma (mean, 12.4% and the incidence of PCNA-positive cells was significantly higher in tumors with p53 expression (P = 0.0226. There was no statistical difference in PCNA values when biological parameters such as Gleason score, tumor volume, extraprostatic involvement, seminal vesicle infiltration or lymph node metastasis were considered. We conclude that proliferative activity is usually low in prostate carcinoma but is correlated with p53 immune staining, indicating that p53 is important in cell cycle control in this neoplasm.

  18. Synthesis and anti-proliferative activity of fluoro-substituted chalcones.

    Science.gov (United States)

    Burmaoglu, Serdar; Algul, Oztekin; Anıl, Derya Aktas; Gobek, Arzu; Duran, Gulay Gulbol; Ersan, Ronak Haj; Duran, Nizami

    2016-07-01

    A series of novel fluoro-substituted chalcone derivatives have been synthesized. All synthesized compounds were characterized by (1)H nuclear magnetic resonance (NMR), (13)C NMR, and elemental analysis. Their anti-proliferative activities were evaluated against five cancer cells lines, namely, A549, A498, HeLa, A375, and HepG2 using the MTT method. Most of the compounds showed moderate to high activity with IC50 values in the range of 0.029-0.729μM. Of all the synthesized compounds, 10 and 19 exhibited the most potent anti-proliferative activities against cancer cells, and 10 was identified as the most promising compound. PMID:27217001

  19. Spontaneous and mitogen-induced proliferative activity of mononuclear cells in patients with pollinosis

    International Nuclear Information System (INIS)

    The induction of the proliferative response of B cells by lipopolysaccharide (LPS) and the proliferative activity of T lymphocytes during stimulation by phytohemagglutinin (PHA) in patients with pollinosis, with hypersensitivity to timothy-grass pollen, were studied. Peripheral blood mononuclear cells (MNC) from 17 patients with pollinosis aged from 16 to 40 years, were used. Lymphocytes (MNC) were isolated form heparinized blood by centrifugation and LPS from E. coli serotype 026:B6 in final concentrations was used as B-cell activator. Tritium-thymidine was added 18 h before the end of the culture time. Incorporated radioactivity was counted in a Mark III liquid scintillation beta-counter. The hyperproduction of IgE observed in atopic patients is more likely to be connected with changes in the later stages of differentiation of IgE-synthesizing B-lymphocytes (at the memory cell level) into IgE-producing plasma cells

  20. Spontaneous and mitogen-induced proliferative activity of mononuclear cells in patients with pollinosis

    Energy Technology Data Exchange (ETDEWEB)

    Serov, A.A.

    1985-06-01

    The induction of the proliferative response of B cells by lipopolysaccharide (LPS) and the proliferative activity of T lymphocytes during stimulation by phytohemagglutinin (PHA) in patients with pollinosis, with hypersensitivity to timothy-grass pollen, were studied. Peripheral blood mononuclear cells (MNC) from 17 patients with pollinosis aged from 16 to 40 years, were used. Lymphocytes (MNC) were isolated form heparinized blood by centrifugation and LPS from E. coli serotype 026:B6 in final concentrations was used as B-cell activator. Tritium-thymidine was added 18 h before the end of the culture time. Incorporated radioactivity was counted in a Mark III liquid scintillation beta-counter. The hyperproduction of IgE observed in atopic patients is more likely to be connected with changes in the later stages of differentiation of IgE-synthesizing B-lymphocytes (at the memory cell level) into IgE-producing plasma cells.

  1. Proliferative activity, DNA synthesis and reproductive death of near and distant descendants of irradiated cells

    International Nuclear Information System (INIS)

    In experiments on HeLa cells a study was made of a change in the rate of DNA synthesis, proliferative activity and reproductive death of exposed cells and their descendants throughout a number of generations. The rate of DNA synthesis decreased in 4 postirradiation generations, and a maximum inhibition (by 50%) was registered 48 h following irradiation. The proliferative activity of the irradiated cell descendants markedly decreased throughout 18-20 generations resulting in an increased death rate and a loss of cells from a generation. It is suggested that even the distant desendants (18-20 generations) of expose cells exhibited some lesions which may, in time, become fatal events leading to cell death

  2. Ultrastructure of canine lung during the proliferative phase of paraquat toxicity.

    OpenAIRE

    Hampson, E. C.; Pond, S M

    1988-01-01

    The herbicide paraquat induces irreversible progressive pulmonary fibrosis in human beings and animals. The mechanisms of the fibrosis are still unresolved. There is histological and ultrastructural evidence that an early destructive phase followed by a proliferative phase occurs in the lungs post paraquat-exposure. In this study, lungs obtained from a dog 7 days following intravenous administration of paraquat (12 mg paraquat dichloride per kg bodyweight) are compared with lungs obtained fro...

  3. Application of Neural Networks to the Classification of Pancreatic Intraductal Proliferative Lesions

    OpenAIRE

    Okoń, Krzysztof; Tomaszewska, Romana; Nowak, Krystyna; Stachura, Jerzy

    2001-01-01

    The aim of the study was to test applycability of neural networks to classification of pancreatic intraductal proliferative lesions basing on nuclear features, especially chromatin texture. Material for the study was obtained from patients operated on for pancreatic cancer, chronic pancreatitis and other tumours requiring pancreatic resection. Intraductal lesions were classified as low and high grade as previously described. The image analysis system consisted of a microscope, CCD camera comb...

  4. Inhibitors of glycoprotein processing alter T-cell proliferative responses to antigen and to interleukin 2.

    OpenAIRE

    Wall, K A; Pierce, J D; Elbein, A D

    1988-01-01

    Most of the cell-surface molecules involved in T-cell immune responses are N-linked glycoproteins. We have investigated the effects of inhibitors of glycoprotein processing on specific T-cell functions, with the dual aims of examining the functional role of carbohydrate and of testing the usefulness of such compounds as immunomodulators. Treatment of a cloned murine helper T-cell line with these inhibitors differentially affects the proliferative response of the cell, depending upon the natur...

  5. Metformin Enhances Anti-proliferative Effect of Cisplatin in Cervical Cancer Cell Line

    OpenAIRE

    Ratih D. Yudhani; Riza N. Pesik; Dono Indarto

    2016-01-01

    Cervival cancer is one of the top rank of gynecological malignancy in the world, leading to high morbidity and mortality rates. Cisplatin is a chemotherapeutic agent that is generally used to treat cervical cancer but the use of this drug is limited because of serious side effects. Metformin, a diabetic drug, decreases not only blood glucose levels but also cell viability of some cancer cells. The aim of this study was to investigate the anti-proliferative effect of combination metformin and ...

  6. Vision-Related Quality of Life and Visual Function Following Vitrectomy for Proliferative Diabetic Retinopathy

    OpenAIRE

    Okamoto, Fumiki; Okamoto, Yoshifumi; Fukuda, Shinichi; Hiraoka, Takahiro; Oshika, Tetsuro

    2008-01-01

    PurposeTo evaluate the vision-related quality of life (VR-QOL) and visual function following vitrectomy for proliferative diabetic retinopathy (PDR).DesignProspective, interventional, consecutive, comparative case series.MethodsThe 25-Item National Eye Institute Visual Function Questionnaire (VFQ-25) was answered by 51 patients with PDR before and three months after 20-gauge pars plana vitrectomy. Among the patients with PDR, 30 underwent combined cataract surgery and vitrectomy. Clinical dat...

  7. Different effects of neurotensin and neuromedin-N on the proliferative activity of rat adrenal cortex

    OpenAIRE

    Markowska, A.; Nussdorfer, G G; Malendowicz, L.K.

    1994-01-01

    Evidence indicates that neurotensin (NT) and neuromedin-N (NMN) exerts an adrenocorticotropic effect in the rat. The present study aimed to investigate whether these neuropeptides are able to stimulate the proliferation of rat adrenocortical cells in vivo and to compare their mode of action. Adrenocortical proliferative activity was assessed by the metaphasearrest technique and metaphases were counted per medulla-containing adrenal section. A bolus administ...

  8. Effects of bombesin and neuromedin-B on the proliferative activity of the rat adrenal cortex

    OpenAIRE

    Markowska, A.; Nussdorfer, G G; Malendowicz, L.K.

    1993-01-01

    Bombesin (BM) and neuromedin-B (NMB) exert similar biological effects, acting via two functionally distinct BM-receptor subtypes. The present study aimed to investigate whether BM and NMB stimulate the proliferation of rat adrenocortical cells and to compare their mode of action. Adult female rats were treated with a single subcutaneous dose of 3 pg BM or NMB. Adrenocortical proliferative activity was assessed by the metaphase-arrest technique. BM administratio...

  9. Human T cell responses to dengue virus antigens. Proliferative responses and interferon gamma production.

    OpenAIRE

    Kurane, I; Innis, B L; Nisalak, A; Hoke, C; Nimmannitya, S; Meager, A.; Ennis, F A

    1989-01-01

    The severe complications of dengue virus infections, hemorrhagic manifestations and shock, are more commonly observed during secondary dengue virus infections than during primary infections. It has been speculated that these complications are mediated by cross-reactive host-immune responses. We have begun to analyze human T cell responses to dengue antigens in vitro to explain the possible role of T lymphocytes in the pathogenesis of these complications. Dengue antigens induce proliferative r...

  10. Proliferative and Transcriptional Identity of Distinct Classes of Neural Precursors in the Mammalian Olfactory Epithelium

    OpenAIRE

    Tucker, Eric S.; Lehtinen, Maria Kristiina; Maynard, Tom; Zirlinger, Mariela; Dulac, Catherine; Rawson, Nancy; Pevny, Larysa; LaMantia, Anthony-Samuel

    2010-01-01

    Neural precursors in the developing olfactory epithelium (OE) give rise to three major neuronal classes – olfactory receptor (ORNs), vomeronasal (VRNs) and gonadotropin releasing hormone (GnRH) neurons. Nevertheless, the molecular and proliferative identities of these precursors are largely unknown. We characterized two precursor classes in the olfactory epithelium (OE) shortly after it becomes a distinct tissue at midgestation in the mouse: slowly dividing self-renewing precursors that expre...

  11. Does preoperative intravitreal bevacizumab reduce complications of vitrectomy for proliferative diabetic retinopathy?

    OpenAIRE

    Daniela Véliz; Gabriel Rada

    2014-01-01

    Proliferative diabetic retinopathy carries a high risk of blindness if it is not timely treated. The treatment many times includes vitrectomy. Bevacizumab, an anti-vascular endothelial growth factor, may decrease intraoperative complications. Searching in Epistemonikos database, which is maintained by screening 20 databases, we identified three systematic reviews including 9 randomized trials. We combined the evidence using meta-analysis and generated a summary of findings table following the...

  12. Effect of Bevacizumab Injection before Vitrectomy on Intravitreal Hemorrhage in Pseudophakic Patients with Proliferative Diabetic Retinopathy

    OpenAIRE

    Mehmet Demir; Ersin Oba; Efe Can; Orhan Kara; Sonmez Cinar

    2013-01-01

    We evaluated the effect of intravitreal bevacizumab (IVB) injection before pars plana vitrectomy (PPV) on intravitreal hemorrhage (VH) during and after vitrectomy for postoperative the first day and the first month in pseudophakic patients with proliferative diabetic retinopathy (PDR). This retrospective study was performed on 44 eyes of 44 patients who underwent vitrectomy for PDR. Patients were divided into PPV (n = 22 eyes) and PPV + IVB (n = 22 eyes) groups. Injection of bevacizumab (1.25...

  13. Ranibizumab in patients with dense cataract and proliferative diabetic retinopathy with rubeosis

    OpenAIRE

    2012-01-01

    Background: To evaluate the safety of ranibizumab as a surgical adjunct during cataract surgery in patients with proliferative diabetic retinopathy (PDR) with rubeosis, and to evaluate the efficacy and adverse effects of ranibizumab in treating PDR with rubeosis. Materials and Methods: Three intravitreal injections of 0.5 mg ranibizumab were administered on day-1, months-1 and -2 with cataract surgery 6-16 days after first injection. Retreatments with ranibizumab injections and pan-retinal ph...

  14. Proliferative responses to canine thyroglobulin of peripheral blood mononuclear cells from hypothyroid dogs.

    Science.gov (United States)

    Tani, Hiroyuki; Nabetani, Tomoyo; Sasai, Kazumi; Baba, Eiichiroh

    2005-04-01

    The immune responses of hypothyroid dogs to canine thyroglobulin (cTg) were evaluated for the proliferative ability of peripheral blood mononuclear cells (PBMC). PBMC from three hypothyroid dogs with high titers of thyroglobulin autoantibody (TgAA) and 3 clinically normal dogs were cultured with 5, 10, or 20 microg/ml of cTg for 72 hr. The proliferative responses of the cells were determined by the level of incorporated BrdU. The numbers of cells expressing Thy-1, CD4, CD8 and IgG in the PBMC were counted by the immunofluorescence method. Proliferative responses to cTg were observed in the cells from hypothyroid dogs. The number of cells expressing IgG and CD8 in the hypothyroid dogs tended to be high compared with the clinically normal dogs. The CD4+ cells in cultures from hypothyroid dogs increased depending upon the amount of cTg. There was a significant (Pdogs. These findings suggest a possible relationship between canine hypothyroidism and cellular immunity. Loss of self tolerance to thyroid antigens in CD4+ T cells may play an important role in the development of canine hypothyroidism. PMID:15876785

  15. In vitro anti-proliferative and anti-angiogenic activities of thalidomide dithiocarbamate analogs.

    Science.gov (United States)

    El-Aarag, Bishoy Y A; Kasai, Tomonari; Zahran, Magdy A H; Zakhary, Nadia I; Shigehiro, Tsukasa; Sekhar, Sreeja C; Agwa, Hussein S; Mizutani, Akifumi; Murakami, Hiroshi; Kakuta, Hiroki; Seno, Masaharu

    2014-08-01

    Inhibition of angiogenesis is currently perceived as a promising strategy in the treatment of cancer. The anti-angiogenicity of thalidomide has inspired a second wave of research on this teratogenic drug. The present study aimed to investigate the anti-proliferative and anti-angiogenic activities of two thalidomide dithiocarbamate analogs by studying their anti-proliferative effects on human umbilical vein endothelial cells (HUVECs) and MDA-MB-231 human breast cancer cell lines. Their action on the expression levels of IL-6, IL-8, TNF-α, VEGF165, and MMP-2 was also assessed. Furthermore, their effect on angiogenesis was evaluated through wound healing, migration, tube formation, and nitric oxide (NO) assays. Results illustrated that the proliferation of HUVECs and MDA-MB-231 cells was not significantly affected by thalidomide at 6.25-100μM. Thalidomide failed to block angiogenesis at similar concentrations. By contrast, thalidomide dithiocarbamate analogs exhibited significant anti-proliferative action on HUVECs and MDA-MB-231 cells without causing cytotoxicity and also showed powerful anti-angiogenicity in wound healing, migration, tube formation, and NO assays. Thalidomide analogs 1 and 2 demonstrated more potent activity to suppress expression levels of IL-6, IL-8, TNF-α, VEGF165, and MMP-2 than thalidomide. Analog 1 consistently, showed the highest potency and efficacy in all the assays. Taken together, our results support further development and evaluation of novel thalidomide analogs as anti-tumor and anti-angiogenic agents. PMID:24859059

  16. Intravitreal Ranibizumab for Stage IV Proliferative Sickle Cell Retinopathy: A First Case Report

    Directory of Open Access Journals (Sweden)

    Panagiotis G. Mitropoulos

    2014-01-01

    Full Text Available Purpose. To present the case of a 27-year-old male patient with stage IV proliferative sickle cell retinopathy, treated with one intravitreal injection of ranibizumab, showing regression of the neovascularization and no recurrence at the 9-month follow-up. Methods. A 27-year-old male patient presented with blurred vision and floaters in the right eye since three days. His best corrected visual acuity was 6/18. Ophthalmological examination and fluorescein angiography revealed proliferative sickle cell retinopathy stage IV with vitreous hemorrhage and sea fan neovascularization, as well as ischemic areas at the temporal periphery. Results. The patient was treated with one intravitreal injection of ranibizumab, presenting improvement in the visual acuity from 6/18 to 6/6, resolution of vitreous hemorrhage, and regression of the neovascularization. Additionally, he underwent scatter laser photocoagulation at the ischemic areas. At the 9-month follow-up there was no recurrence, while no adverse effects were noticed. Conclusions. Intravitreal ranibizumab may be a useful adjunct to laser photocoagulation in the management of proliferative sickle cell retinopathy and may permit some patients to avoid pars plana vitrectomy for vitreous hemorrhage.

  17. Tristetraprolin mediates the anti-proliferative effects of metformin in breast cancer cells.

    Science.gov (United States)

    Pandiri, Indira; Chen, Yingqing; Joe, Yeonsoo; Kim, Hyo Jeong; Park, Jeongmin; Chung, Hun Taeg; Park, Jeong Woo

    2016-02-01

    Metformin, which is a drug commonly prescribed to treat type 2 diabetes, has anti-proliferative effects in cancer cells; however, the molecular mechanisms underlying this effect remain largely unknown. The aim is to investigate the role of tristetraprolin (TTP), an AU-rich element-binding protein, in anti-proliferative effects of metformin in cancer cells. p53 wild-type and p53 mutant breast cancer cells were treated with metformin, and expression of TTP and c-Myc was analyzed by semi-quantitative RT-PCR, Western blots, and promoter activity assay. Breast cancer cells were transfected with siRNA against TTP to inhibit TTP expression or c-Myc and, after metformin treatment, analyzed for cell proliferation by MTS assay. Metformin induces the expression of tristetraprolin (TTP) in breast cancer cells in a p53-independent manner. Importantly, inhibition of TTP abrogated the anti-proliferation effect of metformin. We observed that metformin decreased c-Myc levels, and ectopic expression of c-Myc blocked the effect of metformin on TTP expression and cell proliferation. Our data indicate that metformin induces TTP expression by reducing the expression of c-Myc, suggesting a new model whereby TTP acts as a mediator of metformin's anti-proliferative activity in cancer cells. PMID:26956973

  18. Comparative antitumor and anti-proliferative activities of Hippophae rhamnoides L. leaves extracts

    Directory of Open Access Journals (Sweden)

    Javid Ali

    2015-03-01

    Full Text Available Objective: To evaluate the antitumor and anti-proliferative activities of methanol, aqueous, acetone, ethyl acetate, ethanol, chloroform and n-hexane extracts of Hippophae rhamnoides leaves. Methods: Antitumor activities were evaluated by using the antitumor potato disc assay by using inoculums (Agrobacterium tumefaciens with three different concentrations of test samples (10, 100 and 1 000 mg/L. Anti-proliferative activity was evaluated by the given method of methyl thiazolyl tetrazolium assay. The concentrations of the extract ranging from 0.039 to 10 mg/mL were tested against HeLa cells. Results: Highest tumors inhibition activity (60.9% and 55.8% was shown by methanol and ethanol extracts, with EC50 values of 424.41 and 434.61 mg/L respectively. At 10 mg/mL, The highest cell inhibition 75.61% was observed in methanol extract and the lowest 36.59% were calculated in n-hexane extract. The difference in tumor and cell inhibition (% may be due to the different concentration of active compounds responsible for antitumor and anti-proliferative activities. All extracts have considerable level of tumor and cell inhibitiory effect in a dose dependent manner. Conclusions: Our finding showed that Hippophae rhamnoides leaves are a potent natural source of antitumor and antiproliferative agent.

  19. Anti-oxidant, anti-inflammatory and anti-proliferative activities of Moroccan commercial essential oils.

    Science.gov (United States)

    Aazza, Smail; Lyoussi, Badiaa; Megías, Cristina; Cortés-Giraldo, Isabel; Vioque, Javier; Figueiredo, A Cristina; Miguel, Maria G

    2014-04-01

    Essential oils (EO) possess antimicrobial, anti-inflammatory, insect repellent, anti-cancer, and antioxidant properties, among others. In the present work, the antioxidant, anti-inflammatory and anti-proliferative activities of Moroccan commercial EOs (Citrus aurantium, C. limon, Cupressus sempervirens, Eucalyptus globulus, Foeniculum vulgare and Thymus vulgaris) were evaluated and compared with their main constituents. T. vulgaris EO showed the best free radicals scavenging capacity. This EO was also the most effective against lipid peroxidation along with C. limon and F. vulgare EOs. C. sempervirens EO was the most effective in scavenging NO free radicals, whereas C. limon EO showed the best chelating power. Not all of the major compounds of the EO were responsible for the whole activity of the EOs. T. vulgaris EO showed the best anti-proliferative activity against THP-1 cells in contrast to that of F. vulgare. The antioxidant and anti-inflammatory activities of the EOs were plant species dependent and not always attributable to the EOs main components. Nevertheless, the EOs anti-proliferative activities were more related to their main components, as with T. vulgaris, C. limon, E. globulus and C. sempervirens. PMID:24868891

  20. Quinazolinones-Phenylquinoxaline hybrids with unsaturation/saturation linkers as novel anti-proliferative agents.

    Science.gov (United States)

    Palem, Jyothsna Devi; Alugubelli, Gopi Reddy; Bantu, Rajashaker; Nagarapu, Lingaiah; Polepalli, Sowjanya; Jain, S Nishanth; Bathini, Raju; Manga, Vijjulatha

    2016-07-01

    A new series of novel quinazolinones with allylphenyl quinoxaline hybrids 9a-n were efficiently synthesized in good yields by the reaction of 3-allyl-2-methylquinazolin-4(3H)-one (5a-n) with bromophenyl)quinoxaline (8) utilizing Pd catalyzed Heck-cross coupling and evaluated for anti-proliferative activity against four cancer cell lines such as HeLa (cervical), MIAPACA (pancreatic), MDA-MB-231 (breast) and IMR32 (neuroblastoma). Compounds 9a, 9e, 9g and 9h exhibited promising anti-proliferative activity with GI50 values ranging from 0.06 to 0.2μM against four cell lines, while compounds 9e and 9k showed significant activity against HeLa and MIAPACA cell lines and compounds 9b, 9d, 9h and 9j showed selective potency against IMR32 and MDA-MB-231 cell lines. This is the first report on the synthesis and in vitro anti-proliferative evaluation of E-2-(4-substituted)-3-(3-(4-(quinoxalin-2-yl)phenyl)allyl)quinazolin-4(3H)-ones (9a-n). Docking results indicate a sign of good correlation between experimental activity and calculated binding affinity (dock score), suggesting that these compounds could act as promising DNA intercalates. PMID:27209232

  1. Sporadic Gastric Well-Differentiated Neuroendocrine Tumors Have a Higher Ki-67 Proliferative Index.

    Science.gov (United States)

    Lee, Hee Eun; Mounajjed, Taofic; Erickson, Lori A; Wu, Tsung-Teh

    2016-09-01

    Well-differentiated neuroendocrine tumor (WDNET) of the stomach can arise in three distinct clinical settings: (1) in association with autoimmune atrophic gastritis, (2) in association with multiple neuroendocrine neoplasia type I (MEN I) or Zollinger-Ellison syndrome (ZES), or (3) sporadic. The Ki-67 proliferative index (PI) in gastric WDNETs in these three distinct clinical settings has not been evaluated in detail. Forty-five gastric WNETs underwent polypectomy (n = 4), endoscopic mucosal resection (n = 12), and surgical resection (n = 29) between 1994 and 2015 were included. H&E slides from each case were reviewed, and Ki-67 immunostain was performed on one representative tumor block. Ki-67 PI was determined by quantitative Aperio image analysis software in areas of strongest nuclear labeling ("hot spots"), and correlated with underlying clinical and pathological features. Twenty-one patients were male and 24 female with a median age of 57 years (range, 30-80 years). Tumors were classified as type I (n = 17), type II (n = 6), and type III (n = 22) WDNETs. Types II and III showed more advanced TNM stage compared to type I (p = 0.02, overall). WHO grade based on Ki-67 PI was higher in type III WDNETs [grade 1 (G1), n = 3; grade 2 (G2), n = 15; and grade 3 (G3), n = 4] than in type I WDNETs [G1, n = 5; G2, n = 12] and in type II WDNETs [G1, n = 2; G2, n = 4] (p = 0.050, overall). Ki-67 PI was significantly higher in type III WDNETs (mean ± SD = 13.0 ± 13.3 %) than in non-sporadic (type I and II) WDNETs (mean ± SD = 5.3 ± 3.3 %; p = 0.015). There was no difference in Ki-67 PI between type I WDNETs (mean ± SD = 5.2 ± 3.5 %) and type II WDNETs (mean ± SD = 5.6 ± 3.1%; p = 0.817). Higher Ki-67 PI was associated with higher tumor T stage (p = 0.003) and also tended to be associated with lymph node metastasis (p = 0.071). In the Kaplan-Meier survival analysis, type I was associated with a

  2. Long term outcome of treatment of diffuse proliferative glomerulonephritis with pulse steroids and short course pulse cyclophosphamide

    Directory of Open Access Journals (Sweden)

    S. Bombardieri

    2011-06-01

    Full Text Available Objectives: To evaluate the long- term outcome of a group of systemic lupus erythematosus (SLE patients with diffuse proliferative glomerulonephritis (DPGN treated with pulse steroids and a short course of pulse cyclophosphamide (Cyc in order to find out baseline predictor variables of disease outcome at the end of the follow-up. Methods: Female SLE patients fulfilling ACR criteria with active DPGN treated with pulse steroids and pulse Cyc were enrolled in the study and retrospectively analyzed with particular interest to renal flares and poor renal outcome at the end of follow- up as outcome measures. Results: 30 female patients with DPGN were included, of these 20 (66,7% patients are actually in follow-up at our unit, 4 (13.3% died and 6 (20% were lost during the follow-up. Fourteen patients (46.6% presented at least one renal flare (RF during the follow up for a total of 21 flares. At our last observation, 18 (60% presented a good renal outcome while 12 (40% had a poor outcome. Lower age at kidney biopsy resulted an important prognostic factor for the occurrence of both RF and poor long- term renal outcome; additionally, a poor renal outcome resulted significantly correlated with an inadequate response at the end of the protocol and with the number of renal flares after remission. Conclusions: These data suggest that, in general, a short course therapy with Cyc might be effective in controlling disease activity but demonstrated high rate of RF and poor renal outcome over time; however, this protocol might represent an effective therapeutic strategy in a subgroup of patients with specific epidemiological and clinical characteristics and suggest the possibility of tailoring immunosuppressive therapy on the basis of prognostic factor at baseline.

  3. 樱桃汁和草莓汁激活Nrf2信号通路对砷诱导的人支气管上皮细胞损伤的保护作用%Juices of cherry and strawberry confer protection of human bronchial epithelial cells against arsenic-induced toxicity via activation of Nrf2 signaling pathway

    Institute of Scientific and Technical Information of China (English)

    孔得刚; 王莉莉; 周洪雷; 任冬梅; 娄红祥; 沈涛

    2014-01-01

    目的:研究草莓汁和樱桃汁对NF-E2相关因子2(Nrf2)信号通路的影响,以及两种果汁对砷诱导的人支气管上皮(HBE)细胞损伤的保护作用。方法选择人乳腺癌MDA-MB-231细胞系,分为空白对照组、萝卜硫素组,以及樱桃(草莓)汁1∶10、1∶20、1∶40和1∶80组(果汁稀释比例分别为1∶10、1∶20、1∶40和1∶80),采用抗氧化反应原件(ARE)荧光素酶报告基因和Westerm blotting筛选并确证两种果汁对Nrf2信号通路的影响;选择HBE细胞,分为空白对照组、萝卜硫素组,以及樱桃(草莓)汁1∶10、1∶20、1∶40组(果汁稀释比例分别为1∶10、1∶20和1∶40),采用QuantiChrom谷胱甘肽(GSH)试剂盒测定两种果汁对内源性抗氧化剂GSH水平的影响;采用MTT法和细胞转染技术评价两种果汁对砷诱导的HB E细胞的保护作用。结果草莓汁和樱桃汁能够剂量依赖地增强ARE荧光强度,上调MDA-MB-231细胞中Nrf2及其下游基因NADPH苯醌氧化还原醇(NQO1)和γ-谷氨酰半胱氨酸合成酶(γGCS)蛋白的表达;两种果汁能够提高HBE细胞内源性抗氧化剂GSH水平;两种果汁和砷处理HBE细胞后,果汁预处理的细胞生存率高于砷单独处理的细胞生存率,两种果汁表现出对砷诱导细胞毒性的保护作用,而这种保护作用在转染Nrf2-siRNA后消失。结论草莓汁和樱桃汁通过激活Nrf2信号通路抑制砷诱导的细胞毒性,对HBE细胞具有保护作用。%Objective To investigate the effects of cherry and strawberry juices on NF-E2-related factor 2(Nrf2)signa-ling pathway,and to evaluate their protection effects on arsenic-induced toxicity in human bronchial epithelial (HBE) cells.Methods Human breast cancer 23 1 cells were randomly divided into the control group,sulforaphen treated group,and juice treated groups (juice dilution ratios were 1∶10,1∶20,1∶40 and 1∶80,respectively

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

    International Nuclear Information System (INIS)

    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

  5. Role of local prostaglandin synthesis in the modulation of proliferative activity of rat colonic epithelium.

    OpenAIRE

    Craven, P A; R. Saito; DeRubertis, F R

    1983-01-01

    The role of local prostaglandin (PG) synthesis in the modulation of the proliferative activity of colonic epithelium was examined in rat colon. Experimental rats were given either indomethacin (5 mg/kg s.c. every 8 h for three doses) or aspirin (0.5 g/100 g diet for 3 d). In rats treated with indomethacin or aspirin, the incorporation of [3H]thymidine (dThd) into DNA in vivo was increased approximately twofold over control in mucosal scrapings from distal colon, and approximately threefold ov...

  6. Primary stimulation by dendritic cells induces antiviral proliferative and cytotoxic T cell responses in vitro

    OpenAIRE

    1989-01-01

    We used well-gassed hanging drop (20 microliters) cultures with high concentrations of purified T cells from normal BALB/c mice to examine whether dendritic cells (DC) can induce primary antiviral proliferative T cell responses and generate virus-specific CTL. We found that DC exposed to infectious influenza virus in vitro or in vivo in small numbers (0.1-1%) resulted in strong proliferation of responder T cells within 3 d, and this was strongly inhibited by antibodies to class II MHC molecul...

  7. Spontaneous proliferative lesions and tumors of the uterus of captive African hedgehogs (Atelerix albiventris).

    Science.gov (United States)

    Mikaelian, Igor; Reavill, Drury R; Practice, Avian

    2004-06-01

    Fifteen captive female African hedgehogs (Atelerix albiventris), 3- to 5-yr-old, were diagnosed with proliferative uterine lesions (n = 28). Lesions were associated with vaginal bleeding in all cases, hematuria in 11 of 13 cases, and weight loss in 7 of 12 cases. Lesions were multiple in eight cases and single in seven cases. The lesions identified were 13 adenosarcomas, 7 endometrial stromal sarcomas, 6 endometrial polyps, 1 adenoleiomyosarcoma, and 1 adenoleiomyoma. In one animal with adenosarcoma, peritoneal seeding was detected at the time of hysterectomy. Mean survival time was 303 days (n = 10). Ovariohysterectomy allows prolonged survival of hedgehogs with uterine tumors. PMID:15305518

  8. Continuous wave Nd:YAG laser photocoagulation in proliferative diabetic retinopathy.

    OpenAIRE

    Menchini, U; Lanzetta, P; Soldano, F; Ferrari, E; Virgili, G

    1995-01-01

    AIMS--The therapeutic efficacy of the continuous wave (CW) Nd:YAG laser (working in the free running mode) was investigated in proliferative diabetic retinopathy (PDR) comparing it with a conventional laser source such as the krypton laser. METHODS--Twenty four eyes of 12 patients affected with bilateral PDR were included and divided in two groups. The right eyes were treated with a red krypton laser and the left eyes with a CW Nd:YAG laser. RESULTS--Three months after krypton photocoagulatio...

  9. Response of oral tumors to radiotherapy depending on their proliferative activity

    International Nuclear Information System (INIS)

    A study of the proportion of DNA-synthesizing (label index ) and proliferating cells, and the intensity of DNA synthesis in different zones of the biopsy specimens of 11 patients with cancer of the oral mucosa has shown that squamous cell carcinoma is characterized by a high proliferative activity that may vary in different tumors and in some zones within one tumor. There is a certain correlation between the degree of a decrease of the label index and of the proportion of proliferating cells after irradiation of the focus at a dose of 12 Gy and a complete tumor resorption by the completion of the radiotherapy

  10. Macular Edema Formation and Deterioration of Retinal Function after Intravitreal Bevacizumab Injection for Proliferative Diabetic Retinopathy

    OpenAIRE

    Imai, Hisanori; Honda, Shigeru; Tsukahara, Yasutomo; Negi, Akira

    2011-01-01

    Purpose To report a case of proliferative diabetic retinopathy (PDR) showing transient macular edema (ME) and deteriorated retinal function after intravitreal bevacizumab injection (IVB). Methods and Results A 53-year-old man received IVB (1.25 mg/0.05 ml) in both eyes for the treatment of PDR. There was no treatment-related complication. However, he complained of photopsia in both eyes 6 h after the injection. Slit-lamp examination revealed mild cellular infiltrations (1+) in the anterior ch...

  11. 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

    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...... 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 at the...

  12. 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

    (P = .64) and p53 (P > .32), whereas the MIB-1 index was reduced in the post-chemotherapy specimens (P = .02). The overall, disease-specific survival was 47%, increasing to 54% in patients receiving pre-operative chemotherapy. Statistical analyses showed prognostic impact exclusively by patient age...... regarding angiogenesis (CD34), proliferative activity (MIB-1), and the expression of p53 and MDR (P-glycoprotein (Pgp); clones JSB-1, C494, and MRK16). Quantitative and semiquantitative scores of immunoreactive cells were analyzed statistically along with retrospectively obtained clinicopathologic variables....... Results. Chemotherapy reduced the rate of amputations (P = .00002). The Pgp was overexpressed (score >/=2) in 48% of the primary, diagnostic biopsies, and high Pgp correlated with high Pgp in postsurgical specimens (P = .003). In contrast, no such associations were disclosed for estimates of angiogenesis...

  13. A review of the epidemiologic literature on the role of environmental arsenic exposure and cardiovascular diseases

    International Nuclear Information System (INIS)

    Cardiovascular disease is the leading cause of mortality worldwide. Arsenic is a ubiquitous metalloid in the crust of the earth. Chronic arsenic poisoning is becoming an emerging epidemic in Asia. Epidemiological studies have shown that chronic arsenic poisoning through ingestion of arsenic-contaminated water is associated with various cardiovascular diseases in dose-response relationships. These cardiovascular disorders include carotid atherosclerosis detected by ultrasonography, impaired microcirculation, prolonged QT interval and increased QT dispersion in electrocardiography, and clinical outcomes such as hypertension, blackfoot disease (a unique peripheral vascular disease endemic in southwestern Taiwan), coronary artery disease and cerebral infarction. Chronic arsenic poisoning is an independent risk factor for cardiovascular disease. The adverse cardiovascular effects of long-term arsenic exposure may be persistent and/or irreversible. Arsenic-induced cardiovascular diseases in human population may result from the interaction among genetic, environment and nutritional factors. The major adverse cardiovascular effect of chronic arsenic poisoning has been established qualitatively and quantitatively in the high arsenic exposure areas, but the low-dose effect of arsenic on cardiovascular diseases remains to be explored. Cardiovascular death is the major cause of mortality worldwide, and a small increased risk may imply a large quantity of excess mortality

  14. Apoptosis and proliferative activity of non-Hodgkin's lymphoma: correlation with Bcl-2 and P53 protein expression

    International Nuclear Information System (INIS)

    Tumor growth in a given neoplasm is the net result of cell proliferation and cell loss, and apoptosis is the most significant component of continuous cell loss in most tumors. In this study, we examined non-Hodgkin's lymphoma (NHL, n = 67) immunohistochemically for the presence of Bcl-2 oncoprotein and P53 protein and compared apoptotic indices (Als) and Ki-67 proliferative indices (percentages of Ki-67 positive cells). 67 patients with NHL were evaluated: 3 low-grade and 64 intermediate-grade. The phenotype was determined in 65 cases: 47 (70%) were B cell type and 18 (27%) were T cell type. Als and Ki-67 proliferative indices were determined immunohistochemically and the overexpression of P53 and Bcl-2 protein were also evaluated. The overexpressions of Bcl-2 protein and P53 protein were found in 40% (26/65) and 31% (20/65). The Al ranged from 0% to 15% (mean 2.61, median 1.2). Cellular Bcl-2, which counteracts apoptosis, was significantly (ρ = 0.005) associated with Als. Ki-67 proliferative indices ranged from 1% to 91% (mean 55.4), and P53 was significantly (ρ 0.000) associated with Ki-67 proliferative indices. A positive correlation between Als and Ki-67 proliferative indices was revealed (ρ = 0.012) in Bcl-2 positive patients. In NHL, we observed a correlation between Als and Bcl-2 expression, between Ki-67 proliferative indices and P53 expression, and between Als and Ki-67 proliferative indices in Bcl-2 positive patients. Our results suggest that cell apoptosis may be inseparable from cell proliferation during tumor growth

  15. Age related decline in the proliferative response of human T cells to OKT3 stimulation

    International Nuclear Information System (INIS)

    The level of the in vitro proliferative response of human peripheral blood mononuclear cells (PBMC) to the OKT3 monoclonal antibody is directly related to the level of monocyte representation in the cell population. The responses to OKT3 stimulation of PBMC obtained from different individual are difficult to interpret due to variable percentage representation of monocytes. To eliminate this problem purified T cells from humans of various ages were incubated with 2 ng/ml OKT3 antibody and 10% purified autologous monocytes. The 3H-TdR incorporation of 1 x 105 T cells at 72 hrs of culture was 69,939 +/- 6085 (SEM) cpm for young individuals (mean age 35 yrs) and 33,163 +/- 2962 cpm for healthy elderly individuals (mean age 78 yrs). In addition, IL2 receptors were measured using two color fluorescence and flow cytometry with phycoerythrin conjugated anti-IL2 receptor antibody and FITC conjugated OKT11 antibody. The percentage of cells expressing IL2 receptors was 46% for the cells from the young individuals and 23% for cells from old individuals. These results suggest that the age related decline in the proliferative ability of T cells is partially due to a decreased expression of IL2 receptors and that proliferation and IL2 receptor expression is under the control of monocyte accessory cells

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

    International Nuclear Information System (INIS)

    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)

  17. [Synthesis and anti-proliferative activity of fluoroquinolone (rhodanine unsaturated ketone) amide derivatives].

    Science.gov (United States)

    Gao, Liu-zhou; Xie, Yu-suo; Yan, Qiang; Wu, Shu-min; Ni, Li-li; Zhao, Hui; Huang, Wen-long; Hu, Guo-qiang

    2015-08-01

    To discover novel antitumor rhodanine unsaturated ketones, a series of fluoroquinolone (rhodanine α, β-unsaturated ketone) amine derivatives (5a-5r) were designed and synthesized with fluoroquinolone amide scaffold as a carrier. The structures of eighteen title compounds were characterized by elemental analysis, 1H NMR and MS. The in vitro anti-proliferative activity against Hep-3B, Capan-1 and HL60 cells was evaluated by MTT assay. The results showed that the title compounds not only had more significant anti-proliferative activity against three tested cancer cell lines than that of the parent ciprofloxacin 1, but also exhibited the highest activity against Capan-1 cells. The SAR revealed that some compounds carrying aromatic heterocyclic rings or phenyl attached to an electron-withdrawing carboxyl or sulfonamide substituent were comparable to or better than comparison doxorubicin against Capan-1 cells. As such, it suggests that fluoroquinolone (rhodanine α, β-unsaturated ketone) amines are promising leads for the development of novel antitumor fluoroquinolones or rhodanine analogues. PMID:26669001

  18. Anti-proliferative effects of protein kinase C inhibitors in human keratinocytes.

    Science.gov (United States)

    Hegemann, L; Bonnekoh, B; van Rooijen, L A; Mahrle, G

    1992-07-01

    Various lines of evidence indicate that protein kinase C, a key enzyme in transmembraneous signal transduction, is involved in the regulation of keratinocyte proliferation. In the present study we have investigated the effects of various structurally unrelated protein kinase C inhibitors on the proliferation of HaCa T cells, a non-tumorigenic human keratinocyte cell line. All protein kinase C inhibitors dose-dependently inhibited cell proliferation as assessed by the incorporation of radioactively labelled thymidine and amino acids as well as the increase in total protein content in keratinocytes. The potencies of the drugs to inhibit cell proliferation were strongly correlated to their inhibitory potency on purified protein kinase C, displaying a correlation coefficient of 0.97. Methotrexate, an anti-proliferative drug, was found not to inhibit protein kinase C. Therefore, our data provide evidence that protein kinase C is crucially involved in the regulation of keratinocyte proliferation but is not the only target of anti-proliferative drug action. PMID:1390454

  19. In vitro anti-proliferative and apoptotic activity of different fractions of Artemisia armeniaca

    Directory of Open Access Journals (Sweden)

    Mahdi Mojarrab

    2013-10-01

    Full Text Available Anti-proliferative properties have been reported for certain species of the genus Artemisia.In this study, we investigated the cytotoxic and apoptotic effects of n-hexane, CH2Cl2, EtOAc, n-BuOH and H2O fractions obtained from a crude methanol extract of A. armeniaca on two myeloid cell lines, apoptosis-proficient HL60 cells and apoptosis-resistant K562 cells; in addition, J774 cells were used as a control. Among the solvent fractions of A. armeniaca, the CH2Cl2 fraction was found to have the largest anti-proliferative effect on cancer cells. The IC50 values obtained using an MTS assay for the CH2Cl2 fraction were 75 and 130 µg/ml for HL-60 cells and K562, respectively. The control cells were not significantly affected by this fraction. A flow cytometry histogram of cells treated with the CH2Cl2 fraction of A. armeniacarevealed a sub-G1 peak. DNA fragmentation, increased protein levels of Bax and cleavage of the poly (ADP-ribose polymerase (PARP protein confirmed the induction of apoptosis in cells after a 48-h exposure to the CH2Cl2 fraction. Our results corroborate the cytotoxic and apoptotic effects of the CH2Cl2 fraction of A. armeniaca on K562 and HL-60 cancer cell lines.

  20. Evidence of Anti-Proliferative Activities in Blue Mussel (Mytilus edulis By-Products

    Directory of Open Access Journals (Sweden)

    Marie-Elise Carbonneau

    2013-03-01

    Full Text Available Shellfish waste components contain significant levels of high quality protein and are therefore a potential source for biofunctional high-value peptides. The feasibility of applying a pilot scale enzymatic hydrolysis process to whole Mytilus edulis and, by fractionation, recover hydrolysates presenting a biological activity of interest, was evaluated. Fractions were tested on four immortalized cancerous cell lines: A549, BT549, HCT15 and PC3. The 50 kDa fraction, enriched in peptides, presented anti-proliferative activity with all cell lines and results suggest a bioactive molecule synergy within the fraction. At a protein concentration of 44 µg/mL, the 50 kDa fraction induced a mortality of 90% for PC3, 89% for A549, 85% for HCT15 and of 81% for BT549 cell lines. At the low protein concentration of only 11 µg/mL the 50 kDa fraction still entails a cell mortality of 76% for A549 and 87% for PC3 cell lines. The 50 kDa fraction contains 56% of proteins, 3% of lipids and 6% of minerals on a dry weight basis and the lowest levels detected of taurine and methionine and highest levels of threonine, proline and glycine amino acids. The enzymatic hydrolysis process suggests that Mytilus edulis by-products should be viewed as high-valued products with strong potential as anti-proliferative agent and promising active ingredients in functional foods.

  1. Synthesis and anti-proliferative activity of novel azazerumbone conjugates with chalcones.

    Science.gov (United States)

    Truong, Vuong Van; Nam, Tran Duy; Hung, Truong Ngoc; Nga, Nguyen Thi; Quan, Pham Minh; Chinh, Luu Van; Jung, Sang-Hun

    2015-11-15

    The conjugation of azazerumbone ((3E,7E,11E)-5,5,8,12-tetramethylazacyclododeca-3,7,11-trien-2-one (7)) and 2,4-dihydroxychalcones was carried out for the preparation of novel target compounds 9a-g with 1-ethylene-4-methylene-1,2,3-triazole linker and 10a-f with propylene linker between amide nitrogen of azazerumbone and 4-hydroxy group of chalcone. The anti-proliferative activity of these compounds against the LU-1, Hep-G2, MCF-7 and SW480 human cancer cell lines were significantly improved compared to those of azazerumbone or zerumbone. The anti-proliferative activities of (3E,7E,11E)-1-((1-(2-(3-hydroxy-4-((E)-3-(3-methoxyphenyl)acryloyl)phenoxy)ethyl)-1H-1,2,3-triazol-4-yl)methyl)-5,5,8,12-tetramethyl azacyclododeca-3,7,11-trien-2-one (9b) and (3E,7E,11E)-1-(3-(4-((E)-3-(3,4,5-trimethoxyphenyl)acryloyl)phenoxy)propyl)-5,5,8,12-tetramethylazacyclododeca-3,7,11-trien-2-one (10d) are nearly comparable to those of ellipticine. PMID:26459207

  2. Dashed line relaxing retinotomy in the management of retinal detachment with anterior proliferative vitreoretinopathy

    Directory of Open Access Journals (Sweden)

    Tsen CL

    2015-04-01

    Full Text Available Chui-Lien Tsen,1 Yu-Harn Horng,1 Shwu-Jiuan Sheu1,2 1Department of Ophthalmology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 2School of Medicine, National Yang-Ming University, Taipei, Taiwan Background: We describe the anatomical and functional outcomes of eyes that underwent a modified technique of relaxing retinotomy, dashed line relaxing retinotomy, in the management of retinal detachment with anterior proliferative vitreoretinopathy.Methods: We retrospectively reviewed 54 consecutive eyes in 52 patients who received pars plana vitrectomy with relaxing retinotomy during retinal detachment repair. Perfluorocarbon liquid (PFCL was used as a standard procedure to stabilize the retina during retinotomy to prevent slippage or inversion of the posterior flap. If PFCL was not available due to economic reasons, dashed line relaxing retinotomy was performed instead. Best-corrected visual acuity, slit-lamp biomicroscopy, intraocular pressure measurement, lens status, and fundus examination were analyzed. We excluded patients who were followed up <4 months.Results: Regarding anatomical success rates and visual outcomes, we found no significant differences between patients treated with intraoperative PFCL and those treated with dashed line relaxing retinotomy without PFCL.Conclusion: Compared to the simple and efficient PFCL-assisted relaxing retinotomy, dashed relaxing retinotomy is not the first choice when PFCL is available. Based on our results, this modified technique may offer an alternative in patients with anterior proliferative vitreoretinopathy for whom PFCL is not available. Keywords: perfluorocarbon liquid, PFCL 

  3. Effects of argon laser radiation on aortic endothelial cells: Early membrane changes and proliferative response

    International Nuclear Information System (INIS)

    Membrane fluidity, transmembrane signaling responses, and proliferative characteristics of endothelial cells were studied to characterize biochemical and molecular changes after treatment with argon laser energy. Bovine aortic endothelial cells grown in monolayers were irradiated at 50, 100, and 200 J with an argon laser (wavelength, 488 and 514 nm). Proliferation, assayed by [3H]thymidine incorporation, was measured daily for 6 days. An initial lag phase was observed for irradiated cells when compared to nonirradiated controls (P less than 0.03), with eventual recovery by the third day. Membrane fluidity, determined by fluorescence anisotropy, was measured 1 hr after irradiation. A decrease in static rotational motion of 1,6-diphenyl-1,3,5-hexatriene (DPH) was noted in irradiated versus nonirradiated cells indicating a decrease in membrane fluidity (P less than 0.02). Dynamic studies of intracellular calcium and pH flux utilizing fluorescent probes demonstrated a preserved response to mitogenic stimulation. An increase in intracellular Ca2+ with a concomitant alkalinization of the intracellular milieu was observed in irradiated and non-irradiated cells in response to stimulation with endothelial cell growth factor (ECGF). These responses resemble those characterized for other mitogens. Argon laser energy applied to aortic endothelial cells decreases membrane fluidity early after irradiation. These alterations probably cause the initial lag observed in their proliferative response; however, the capacity to respond to exogenous mitogenic stimulation is maintained

  4. 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

  5. Anti-proliferative activity of Fumaria vaillantii extracts on different cancer cell lines

    Directory of Open Access Journals (Sweden)

    Fatemeh Haji Abbas Tabrizi

    2016-01-01

    Full Text Available Plant-derived natural products are known to have cancer chemo-preventive and chemo-therapeutic properties. Plant extracts or their active constituents are used as folk medicine in traditional therapies by 80% of the world population. The aim of the present study was to determine the anti-proliferative potential of Fumaria vaillantii extracts on three different cancer cell lines including malignant melanoma SKMEL-3, human breast adenocarcinoma MCF-7 and human myelogenous leukemia K562 as well as human gingival fibroblast (HGF as normal cell line. Anti-proliferative activity was evaluated by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT, flowcytometry and annexin methods. Total phenolics and flavonoids were determined by Folin-Ciocalteu and aluminum chloride methods. Chloroform fraction had the lowest IC 50 value at 72 h (0.1 μg/ml in MCF-7 cells. Flowcytometry and annexin-V analysis indicated that the chloroform fraction induced necrosis in MCF-7 cells. In addition, the colorimetric methods showed that the methanolic fraction possessed the highest amount of total phenolics (33.03 ± 0.75 mg/g of dry powder and flavonoids (10.5 ± 2.0 mg/g of dry powder.The collective data demonstrated that F. vaillantii chloroform fraction may contain effective compounds with chemo-therapeutic potential act through an apoptotic independent pathway.

  6. 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.

  7. RNase L Attenuates Mitogen-stimulated Gene Expression via Transcriptional and Post-transcriptional Mechanisms to Limit the Proliferative Response*

    Science.gov (United States)

    Brennan-Laun, Sarah E.; Li, Xiao-Ling; Ezelle, Heather J.; Venkataraman, Thiagarajan; Blackshear, Perry J.; Wilson, Gerald M.; Hassel, Bret A.

    2014-01-01

    The cellular response to mitogens is tightly regulated via transcriptional and post-transcriptional mechanisms to rapidly induce genes that promote proliferation and efficiently attenuate their expression to prevent malignant growth. RNase L is an endoribonuclease that mediates diverse antiproliferative activities, and tristetraprolin (TTP) is a mitogen-induced RNA-binding protein that directs the decay of proliferation-stimulatory mRNAs. In light of their roles as endogenous proliferative constraints, we examined the mechanisms and functional interactions of RNase L and TTP to attenuate a mitogenic response. Mitogen stimulation of RNase L-deficient cells significantly increased TTP transcription and the induction of other mitogen-induced mRNAs. This regulation corresponded with elevated expression of serum-response factor (SRF), a master regulator of mitogen-induced transcription. RNase L destabilized the SRF transcript and formed a complex with SRF mRNA in cells providing a mechanism by which RNase L down-regulates SRF-induced genes. TTP and RNase L proteins interacted in cells suggesting that RNase L is directed to cleave TTP-bound RNAs as a mechanism of substrate specificity. Consistent with their concerted function in RNA turnover, the absence of either RNase L or TTP stabilized SRF mRNA, and a subset of established TTP targets was also regulated by RNase L. RNase L deficiency enhanced mitogen-induced proliferation demonstrating its functional role in limiting the mitogenic response. Our findings support a model of feedback regulation in which RNase L and TTP target SRF mRNA and SRF-induced transcripts. Accordingly, meta-analysis revealed an enrichment of RNase L and TTP targets among SRF-regulated genes suggesting that the RNase L/TTP axis represents a viable target to inhibit SRF-driven proliferation in neoplastic diseases. PMID:25301952

  8. RNase L attenuates mitogen-stimulated gene expression via transcriptional and post-transcriptional mechanisms to limit the proliferative response.

    Science.gov (United States)

    Brennan-Laun, Sarah E; Li, Xiao-Ling; Ezelle, Heather J; Venkataraman, Thiagarajan; Blackshear, Perry J; Wilson, Gerald M; Hassel, Bret A

    2014-11-28

    The cellular response to mitogens is tightly regulated via transcriptional and post-transcriptional mechanisms to rapidly induce genes that promote proliferation and efficiently attenuate their expression to prevent malignant growth. RNase L is an endoribonuclease that mediates diverse antiproliferative activities, and tristetraprolin (TTP) is a mitogen-induced RNA-binding protein that directs the decay of proliferation-stimulatory mRNAs. In light of their roles as endogenous proliferative constraints, we examined the mechanisms and functional interactions of RNase L and TTP to attenuate a mitogenic response. Mitogen stimulation of RNase L-deficient cells significantly increased TTP transcription and the induction of other mitogen-induced mRNAs. This regulation corresponded with elevated expression of serum-response factor (SRF), a master regulator of mitogen-induced transcription. RNase L destabilized the SRF transcript and formed a complex with SRF mRNA in cells providing a mechanism by which RNase L down-regulates SRF-induced genes. TTP and RNase L proteins interacted in cells suggesting that RNase L is directed to cleave TTP-bound RNAs as a mechanism of substrate specificity. Consistent with their concerted function in RNA turnover, the absence of either RNase L or TTP stabilized SRF mRNA, and a subset of established TTP targets was also regulated by RNase L. RNase L deficiency enhanced mitogen-induced proliferation demonstrating its functional role in limiting the mitogenic response. Our findings support a model of feedback regulation in which RNase L and TTP target SRF mRNA and SRF-induced transcripts. Accordingly, meta-analysis revealed an enrichment of RNase L and TTP targets among SRF-regulated genes suggesting that the RNase L/TTP axis represents a viable target to inhibit SRF-driven proliferation in neoplastic diseases. PMID:25301952

  9. Human serum-derived hydroxy long-chain fatty acids exhibit anti-inflammatory and anti-proliferative activity

    Directory of Open Access Journals (Sweden)

    Ahiahonu Pearson

    2011-05-01

    Full Text Available Abstract Background Circulating levels of novel long-chain hydroxy fatty acids (called GTAs were recently discovered in the serum of healthy subjects which were shown to be reduced in subjects with colorectal cancer (CRC, independent of tumor burden or disease stage. The levels of GTAs were subsequently observed to exhibit an inverse association with age in the general population. The current work investigates the biological activity of these fatty acids by evaluating the effects of enriched human serum extracts on cell growth and inflammation. Methods GTAs were extracted from commercially available bulk human serum and then chromatographically separated into enriched (GTA-positive and depleted (GTA-negative fractions. SW620, MCF7 and LPS stimulated RAW264.7 cells were treated with various concentrations of the GTA-positive and GTA-negative extracts, and the effects on cell growth and inflammation determined. Results Enriched fractions resulted in poly-ADP ribose polymerase (PARP cleavage, suppression of NFκB, induction of IκBα, and reduction in NOS2 mRNA transcript levels. In RAW264.7 mouse macrophage cells, incubation with enriched fractions prior to treatment with LPS blocked the induction of several pro-inflammatory markers including nitric oxide, TNFα, IL-1β, NOS2 and COX2. Conclusions Our results show that human serum extracts enriched with endogenous long-chain hydroxy fatty acids possess anti-inflammatory and anti-proliferative activity. These findings support a hypothesis that the reduction of these metabolites with age may result in a compromised ability to defend against uncontrolled cell growth and inflammation, and could therefore represent a significant risk for the development of CRC.

  10. Evidence for a new segregant series of B cell antigens that are encoded in the HLA-D region and that stimulate secondary allogenic proliferative and cytotoxic responses

    OpenAIRE

    1980-01-01

    Five new histocompatibility antigens, designated secondary B cell or (SB) antigens, have been identified by secondary allogeneic proliferative and cytotoxic responses. The reagents used to define the SB antigents are lymphocytes primed between donors matched for all known HLA antigens. The SB antigens stimulate weak primary allogeneic proliferative responses (a mean relative response of 8%) but strong secondary proliferative responses. Strong secondary cell-mediated cytotoxicity is generated ...

  11. 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.

  12. 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.

  13. Effects of dsRNA on proliferative reaction and UDS of splenocytes in X-irradiated mice

    International Nuclear Information System (INIS)

    The effects of different concentrations of dsRNA on proliferative reaction of splenocytes induced by ConA and LPS and on UDS of splenocytes in 1.5 Gy X-irradiated mice are reported. The results show that the proliferative reaction of splenocytes induced by ConA and LPS in experimental groups increased significantly compared with that in positive group, and show that UDS in experimental groups was also much enhanced compared with that in positive group when concentration of dsRNA was higher than 6.25 mg/kg body weight. It is suggested that dsRNA increases proliferative reaction of splenocytes induced by ConA and LPA and inhibits decrease of UDS induced by X-rays

  14. 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. PMID:26730066

  15. THE EXPRESSION OF p16 AND CYCLIN D1 IN PROLIFERATIVE ENDOMETRIUM AND ENDOMETRIAL CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To studythe role of p16 and cyclin in the genesis and development of endometrial car-cinoma. Methods 12 cases of normal endometrium, 22 cases of proliferative endometrium and 41 cases of endome- trial carcinoma were detected for the expression of p16 and cyclin D1 by means of immunohistochemical S-P. Results In normal endometrium p16 was expressed while cyclm D1was almost negative in the proliferative phase, but both of them were negative in the secretory phase. Among the groups of the simple and compound hyperplasia, the atypical hyperplasia and the endometrial carcinoma,the expression of p16 showed a descending tendency, while the expression of cyclin showed an ascending tendency. In endometrial carcinomas the expression of p16 was significantly lower than that of normal endometrium and proliferative endometrium (P<0. 01 ,P<0.05). However, the expression of cy- clin in proliferate endometrium and endometrial carcinoma was significantly higher than that in normal endometri- un (P<0. 05,P<0. 01). The overexpression of cyclin D1 in the atypical hyperplasia group was obviously different from that in the simple and compound hyperplasia group (P<0.01). In endometrial carcinoma,the expression of p16 was decreasing with the descending of cell differentiate degree, on the opposite, the expression of cyclin was in-creased and there existed a negative correlation between them. It was also observed that the overexpression of cyclin was significant different between and ( P <0. 01 ). Conclusion p1 6 is a negative regulating factor of cell cycle in endometrial carcinoma, while cyclin is a positive one. Both of them are important in the genesis and devel-opment of endometrial carcinoma. The Iow expression of p1 6 and the overexpression of cyclin are related with the malicious biological behaviors of endometrial carcinoma and maybe play an important role in the judgement of prog- nosis. Overexpression of cyclin may be an earlier molecular event in the genesis of

  16. Persistent spontaneous synovial drainage from digital flexor sheath in proliferative tenosynovitis: Two case reports and a review of the literature.

    Science.gov (United States)

    Chin, Brian; Cheung, Kevin; Farhangkhoee, Hana; Thoma, Achilleas

    2015-01-01

    Proliferative flexor tenosynovitis of the hand is an inflammatory process involving the synovial sheaths surrounding the tendons. It is most commonly caused by infection, but may also be caused by overuse, diabetes and rheumatic conditions such as rheumatoid arthritis and crystal arthropathies. The present report describes two patients with severe proliferative tenosynovitis, who developed a fistula between the tendon sheath and skin after instrumentation, resulting in persistent synovial drainage. After failing conservative management, both patients were managed with extensive flexor tenosynovectomy to prevent inoculation of bacteria into the flexor sheath. The presentation, management and outcome of each case is described in addition to a discussion of the literature on tenosynovial fistulas. PMID:26090353

  17. Specific detection of Lawsonia intracellularis in porcine proliferative enteropathy inferred from fluorescent rRNA in situ hybridization

    DEFF Research Database (Denmark)

    Boye, Mette; Jensen, Tim Kåre; Møller, Kristian;

    1998-01-01

    probe was determined by simultaneous comparison with indirect immunofluorescence assay for detection of L. intracellularis in formalin-fixed tissue samples from 15 pigs affected by porcine proliferative enteropathy. We used 10 tissue samples from pigs without proliferative mucosal changes as negative...... controls. The results showed that the oligonucleotide probe is specific for L. intracellularis and that fluorescent in situ hybridization targeting ribosomal RNA is a suitable and fast method for specific detection and histological recognition of L. intracellularis in formalin-fixed tissue....

  18. Bilateral proliferative retinopathy as the initial presentation of chronic myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Mafalda S. F. Macedo

    2013-01-01

    Full Text Available 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.

  19. Differential-diagnostic signs of proliferative and nonproliferative mastopathy according to roentgenomorphological correlations

    International Nuclear Information System (INIS)

    In examining the breast of women of different age with nodular and diffuse nodular mastopathy the correlation og mammography and morphology including histotopography findings, made it possible to establish that a palpated lump in proliferative mastopathy corresponded to an nonhomogenous darkening of an irregular rounded shape with obscure uneven contours formed by a great amount of large focus shadows. In nonproliferative mastopathy, nodularity corresponded to a homogenous intense polygonal darkening with clear un even contours. In young women (under 40), the darkening exceeds the size of a palpated lump which is determined by a regular intensity of shadows formed by the field of fibrosclerosis (mastopathy) and surrounding well developed connective and glandular tissue. Clinical findings are of vital importance in the differentiation of nonproliferative mastopathy and normal in young women

  20. Roles of elevated intravitreal IL-1β and IL-10 levels in proliferative diabetic retinopathy

    Directory of Open Access Journals (Sweden)

    Chunjie Mao

    2014-01-01

    Full Text Available Purpose: To determine the roles of interleukin (IL-1β and IL-10 in the vitreous of proliferative diabetic retinopathy (PDR. Materials and Methods: Vitreous samples were obtained from 26 eyes of 26 patients with PDR and from eight eyes of eight cases without PDR. The IL-1β and IL-10 concentration in the vitreous was measured by using an enzyme-linked immunosorbent assay (ELISA. Results: Levels of IL-1β and IL-10 in vitreous were higher in PDR patients compared with control group. And there was significantly negative correlation between IL-1β and IL-10 in control group (r = −0.795; P = 0.032, whereas there was no significant correlation in PDR group (r = 0.176; P = 0.391. Conclusion: Levels of IL-1β and IL-10 were upregulated in vitreous of PDR patients, and these two cytokines play roles in regulating the development and progression of PDR.

  1. Proliferative response of human marginal gingiva to phlogistic process and titanium implant.

    Science.gov (United States)

    Bianconi, R; Cetrullo, N; Vallania, G; Baratta, B; Galanzi, A; Rizzoli, R; Savelli, V; Mazzotti, G

    1993-12-01

    In order to detect proliferative processes in human marginal gingiva in pathological conditions and after externalization of titanium implants, we have attempted BrdU incorporation after "in vitro" incubation of tissue fragments. In comparison with healthy controls, immunocytochemical detection of samples from patients affected by hypertrophic gengivitis shows a good number of proliferating cells in the basal layer of the epithelium, while only in one case can positiveness be detected after externalization of titanium implants. Since after reduction of inflammation by hygienic treatment a low number of proliferating cells can be observed only in the regions where pathological alterations are also present, we suggest that the increase in tissue proliferation may be closely dependent on the intensity of the inflammatory process. All these data demonstrate that in vitro BrdU incubation of tissue fragments represents a suitable method to evaluate cell proliferation in human tissue. PMID:8003287

  2. Mitochondrial localization of the low level p53 protein in proliferative cells

    International Nuclear Information System (INIS)

    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.

  3. 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.

  4. Restoration of proliferative response to M. leprae antigens in lepromatous T cells against candidate antileprosy vaccines.

    Science.gov (United States)

    Mustafa, A S

    1996-09-01

    Several studies conducted in the last decade suggest that Mycobacterium lepraereactive T cells exist in lepromatous patients, but their number may be too few to yield a detectable response in cell-mediated immunity (CMI) assays. Immunizations with candidate antileprosy vaccines and stimulation of T cells with M. leprae + interleukin-2 restore the M. leprae-induced CMI response in lepromatous leprosy patients. These immunizations and stimulation may enrich the pre-existing M. leprae-responsive T cells in lepromatous patients and, thereby, induce a detectable CMI response to M. leprae antigens upon repeat testing. To verify this proposition, we carried out a study in a group of 10 lepromatous leprosy patients. Peripheral blood mononuclear cells (PBMC) obtained from these patients were anergic to M. leprae antigens in proliferative assays, but they responded to the antigens of candidate antileprosy vaccines, i.e., M. bovis BCG, M. bovis BCG + M. leprae, and Mycobacterium w. The enrichment of M. leprae-responsive T cells was performed by establishing T-cell lines from the PBMC after in vitro stimulation with M. leprae, M. bovis BCG, M. bovis BCG + M. leprae, and Mycobacterium w. When tested for their proliferative responses, 1/10, 3/10, 6/10 and 2/10 T-cell lines established against M. leprae, M. bovis BCG, M. bovis BCG + M. leprae, and Mycobacterium w, respectively, responded to M. leprae. These results suggest that enrichment of pre-existing M. leprae-responsive T cells may contribute to the restoration of the T-cell response to M. leprae in some lepromatous patients. Four of the 10 M. leprae-induced T-cell lines proliferated in response to the 65 kDa, 36 kDa, 28 kDa, and 12 kDa recombinant antigens of M. leprae, suggesting that the nonresponsiveness of T cells in some lepromatous patients may be overcome by using recombinant antigens of M. leprae. PMID:8862259

  5. 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.

  6. Buformin exhibits anti-proliferative and anti-invasive effects in endometrial cancer cells

    Science.gov (United States)

    Kilgore, Joshua; Jackson, Amanda L; Clark, Leslie H; Guo, Hui; Zhang, Lu; Jones, Hannah M; Gilliam, Timothy P; Gehrig, Paola A; Zhou, Chunxiao; Bae-Jump, Victoria L

    2016-01-01

    Objective: Biguanides are anti-diabetic drugs that are thought to have anti-tumorigenic effects. Most pre-clinical studies have focused on metformin for cancer treatment and prevention; however, buformin may be potentially more potent than metformin. Given this, our goal was to evaluate the effects of buformin on cell growth, adhesion and invasion in endometrial cancer cell lines. Methods: The ECC-1 and Ishikawa endometrial cancer cell lines were used. Cell proliferation was assessed by MTT assay. Apoptosis and cell cycle analysis was performed by FITC Annexin V assay and propidium iodide staining, respectively. Adhesion was analyzed using the laminin adhesion assay. Invasion was assessed using the transwell invasion assay. The effects of buformin on the AMPK/mTOR pathway were determined by Western immunoblotting. Results: Buformin and metformin inhibited cell proliferation in a dose-dependent manner in both endometrial cancer cell lines. IC50s were 1.4-1.6 mM for metformin and 8-150 μM for buformin. Buformin induced cell cycle G1 phase arrest in the ECC-1 cells and G2 phase arrest in the Ishikawa cells. For both ECC-1 and Ishikawa cells, treatment with buformin resulted in induction of apoptosis, reduction in adhesion and invasion, activation of AMPK and inhibition of phosphorylated-S6. Buformin potentiated the anti-proliferative effects of paclitaxel in both cell lines. Conclusion: Buformin has significant anti-proliferative and anti-metastatic effects in endometrial cancer cells through modulation of the AMPK/mTOR pathway. IC50 values were lower for buformin than metformin, suggesting that buformin may be more potent for endometrial cancer treatment and worthy of further investigation. PMID:27398153

  7. Induction of IgA and sustained deficiency of cell proliferative response in chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Yalena Amador-Ca(n)izares; Liz Alvarez-Lajonchere; Ivis Guerra; Ingrid Rodnguez-Alonso; Gillian Martínez-Donato; Julián Triana; Eddy E González-Horta; Angel Pérez; Santiago Due(n)as-Carrera

    2008-01-01

    AIM: In the present study, antibody and peripheral blood mononuclear cells (PBMC) proliferative responses against hepatitis C virus (HCV) antigens were evaluated in HCV chronically infected patients. METHODS: Paired serum and PBMC samples were taken six months apart from 34 individuals, either treated or not, and tested by enzyme-linked immunosorbent assay (ELISA) and carboxyfluorescein succinimidyl ester staining.RESULTS: Over 70% of the patients showed specific IgG and IgM against capsid, E1 and NS3, while HVR-1 was recognized by half of the patients. An increase in the levels of the anti-capsid IgM (P = 0.027) and IgG (P=0.0006) was observed in six-month samples, compared to baseline. Similarly, a significantly higher percent of patients had detectable IgA reactivity to capsid (P=0.017) and NS3 (P=0.005) after six months, compared to baseline. Particularly, IgA against structural antigens positively correlated with hepatic damage (P=0.036). IgG subclasses evaluation against capsid and NS3 revealed a positive recognition mediated by IgG1 in more than 80% of the individuals. On the contrary, less than 30% of the patients showed a positive proliferative response either of CD4+ or CD8+ T cells, being the capsid poorly recognized. CONCLUSION: These results confirm that while the cellular immune response is narrow and weak, a broad and vigorous humoral response occurs in HCV chronic infection. The observed correlation between IgA and hepatic damage may have diagnostic significance, although it warrants further confirmation.

  8. 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

  9. PROGNOSTIC SIGNIFICANCE OF PROLIFERATIVE ACTIVITY (KI67 EXPRESSION IN OSTEOSARCOMA IN CHILDREN

    Directory of Open Access Journals (Sweden)

    Moumita

    2014-05-01

    Full Text Available BACKGROUND: Osteosarcoma is the commonest primary malignant bone tumor in children. The treatment involves extensive and sometimes life threatening chemotherapy and mutilating surgery. The study of cell proliferation by Ki67 immunohistochemistry has been extensively analyzed in different cancers as a prognostic marker but little information is available in the field of osteosarcoma. The purpose of this study was to evaluate the expression of Ki67 activity in different histological types and grades of osteosarcoma and to evaluate whether higher Ki-67 expression in osteosarcoma can predict the clinical outcome. METHODS: The study was conducted with 30 patients of osteosarcoma. There were 19 boys and 11girls. The mean age was 12.8 yrs. We received the specimens of incisional biopsy of the suspected lesions. All the patients were treated similarly following diagnosis (chemotherapy, definitive surgery followed by chemotherapy and they were followed up for 24 months from the date of diagnosis. Histological type and grade were determined by examining the Hematoxylin and Eosin stained slides. Proliferative activity (Ki67 expression was measured immunohistochemically using MIB-1 antibody. Proliferation was quantitated by counting the number of immunopositive nuclei, detected manually under light microscope. Proliferation index was evaluated in relation to histological grade and survival. RESULTS AND CONCLUSION: We found 12 cases of low grade and 18 cases of high grade osteosarcomas. The mean of Ki67 LI in low grade osteosarcoma was seen 9.9 whereas in high grade osteosarcoma the mean was 21.6. A significant positive correlation between Ki67 LI and histological grade was observed in osteosarcomas (p <0.001. There was no statistically significant correlation found between Ki67LI and the histologic types of osteosarcomas. We followed up all the cases for 24 months; a worse prognosis was observed in osteosarcomas of higher proliferative activity

  10. Reduced proliferative and differentiative activity of mouse pink-eyed dilution melanoblasts is related to apoptosis.

    Science.gov (United States)

    Hirobe, Tomohisa; Terunuma, Emi

    2012-11-01

    The mouse pink-eyed dilution (p) locus is known to control the melanin content, melanosome morphology, and tyrosinase activity in melanocytes. However, it is not well known whether the p allele is involved in regulating melanocyte proliferation, differentiation, and death. The aim of this study is to investigate in detail the role of the p allele in melanocyte proliferation, differentiation, and death using a cell culture system. The epidermal cell suspensions of the neonatal dorsal skin derived from wild type mice at the p locus (black, C57BL/10JHir-P/P) and their congenic mutant (pink-eyed dilution, C57BL/10JHir-p/p) were cultured with serum-free melanoblast-proliferation medium (MDMDF) and melanocyte-proliferation medium (MDMD). The proliferation and differentiation of p/p melanoblasts in MDMDF or MDMD were greatly inhibited compared with those of P/P melanoblasts and melanocytes. It is possible that apoptosis is related to the reduced proliferative and differentiative activity of p/p melanoblasts/melanocytes. The addition of apoptosis-inhibitors, such as caspase-9 inhibitor (C9I) and Bax-inhibiting peptide (BIP) into MDMDF or MDMD stimulated the proliferation and differentiation of p/p melanoblasts. In contrast, in P/P melanoblasts and melanocytes, C9I and BIP failed to stimulate their proliferation and differentiation. The number of apoptotic keratinocytes and melanoblasts/melanocytes in p/p mice was greater than in P/P mice. Moreover, expression of C9 and Bax in keratinocytes and melanoblasts/melanocytes in p/p mice was greater than in P/P mice. These results suggest that the increased apoptosis in keratinocytes and melanoblasts/melanocytes is related to the reduced proliferative and differentiative activity of p/p melanoblasts. PMID:23106556

  11. 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.

  12. 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

  13. Serum MiRNA Biomarkers serve as a Fingerprint for Proliferative Diabetic Retinopathy

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    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.

  14. Immunity to leprosy. II. Genetic control of murine T cell proliferative responses to Mycobacterium leprae.

    Science.gov (United States)

    Douglas-Jones, A G; Watson, J D

    1985-10-01

    T cell proliferative responses to Mycobacterium leprae were measured after immunization of mice at the base of the tail with antigen and challenging lymphocytes from draining lymph nodes in culture with M. leprae. This T cell response to M. leprae has been compared in 18 inbred strains of mice. C57BL/10J mice were identified as low responder mice. The congenic strains B10.M and B10.Q were found to be high responders, whereas B10.BR and B10.P were low responders. F1 (B10.M X C57BL/10J) and F1 (B10.Q X C57BL/10J) hybrid mice were found to be low responders, similar to the C57BL/10J parent, indicating that the low responsive trait is dominant. Whereas B10.BR mice were shown to be low responders to M. leprae, B10.AKM and B10.A(2R) were clearly high responders, indicating that the H-2D region influences the magnitude of the T cell proliferative response. Gene complementation within the H-2 region was evident. Genes outside the H-2 region were also shown to influence the response to M. leprae. C3H/HeN were shown to be high responder mice, whereas other H-2k strains, BALB.K, CBA/N, and B10.BR, were low responders. Gene loci that influence the T cell proliferation assay have been discussed and were compared to known background genes which may be important for the growth of intracellular parasites. Because mycobacteria are intracellular parasites for antigen-presenting cells, genes that affect bacterial growth in these cells will also influence subsequent immune responses of the host. PMID:3928757

  15. Hand-Schüller-Christian disease

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    Deepak Bhargava

    2012-01-01

    Full Text Available Langerhan cell histiocytosis, formerly known as histiocytosis X, traditionally denotes a group of diseases that stem from proliferative reticuloendothelial disturbances.The etiology and pathogenesis of the disease remain debatable. In this paper we report a case of Langerhan cell histiocytosis in a 3 1 / 2 -year-old child who reported to the department of oral pathology with gingival enlargements. The radiological features and histopathological features are also discussed.

  16. 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.

  17. 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...

  18. 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.

  19. Oleuropein ameliorates arsenic induced oxidative stress in mice.

    Science.gov (United States)

    Ogun, Metin; Ozcan, Ayla; Karaman, Musa; Merhan, Oguz; Ozen, Hasan; Kukurt, Abdulsamed; Karapehlivan, Mahmut

    2016-07-01

    The objective of this study is to investigate the potential preventive effect of oleuropein in an experimental arsenic toxicity in mice. For this purpose, mice were exposed to 5mg/kg/day sodium arsenite (NaAsO2) in drinking water and treated with 30mg/kg/day oleuropein for 15 days. At the end of the experiment, animals were sacrificed and selected organs were processed for biochemical and histopahtological investigations. Blood, liver, kidney and brain malondialdehyde (MDA) and nitric oxide (NO) levels were determined by colorimetric methods. Protein carbonyl content is measured by a commercial kit. Liver morphology and immunoreactivity for inducible NOS (iNOS) and endothelial NOS (eNOS) was evaluated microscopically. Level of NO was determined to decrease in blood and tissues whereas MDA increased in arsenic given mice. Tissue protein carbonyl content also increased in this group. Immunoreactivity for iNOS and eNOS was noted to increase with arsenic treatment. Oleuropein treatment had significant effects in normalizing the MDA and NO levels as well as protein carbonyl content. Immunohistochemical staining also showed reduction of the expression of iNOS and eNOS in liver. The results indicate that oleuropein ameliorates oxidative tissue damage by scavenging free radicals. PMID:27259345

  20. Increased melatonin levels in aqueous humor of patients with proliferative retinopathy in type 2 diabetes mellitus

    Science.gov (United States)

    Aydin, Erdinc; Sahin, Semsettin

    2016-01-01

    AIM To report the association between melatonin levels in aqueous humor and serum, and diabetic retinopathy (DR) grade in type 2 diabetic patients. METHODS Aqueous humor and plasma samples from 26 patients with DR (in nonproliferative and proliferative stages) and 14 control subjects were collected during cataract surgery after 6 p.m. Melatonin concentrations were determined using an enzyme-linked immunosorbent assay (ELISA). RESULTS Melatonin levels were significantly higher in the aqueous humor of patients with proliferative diabetic retinopathy (PDR) [18.57±2.67 pg/mL (range 15.20-23.06) vs 13.63±2.71 pg/mL (range 10.20-20.20), P=0.0001], but not in those with nonproliferative retinopathy (NPDR) [13.79±2.56 pg/mL (range 9.80-20.10) vs 13.63±2.71 pg/mL (range 10.20-20.20), P=0.961] compared to controls. There was decrement in the plasma melatonin level of patients with PDR, but no significant differences between the plasma melatonin levels of the study groups [5.37±1.74 pg/mL (range 2.85-8.65) vs 6.11±1.90 pg/mL (range 3.13-9.41), P=0.293], or between control and DR groups [NPDR 6.11±1.90 pg/mL (range 3.13-9.41) vs control 6.15±1.91 pg/mL (range 2.18-9.86); PDR (5.37±1.74 pg/mL (range 2.85-8.65) vs control 6.15±1.91 pg/mL (range 2.18-9.86), P=0.808, P=0.264]. CONCLUSION Elevated melatonin levels in aqueous humor in PDR may indicate the level to be associated with DR severity. PMID:27275429

  1. Nuclear Morphometry and Ki67 Proliferative Marker in Renal Clear Cell Carcinoma

    International Nuclear Information System (INIS)

    Different grading systems for renal cell carcinoma (RCC) were proposed to assess patients' outcome. lnterobserver variability interfere with the widespread acceptance. Study of the tumor proliferative activity could provide another parameter for predicting biologic aggression and subsequent prognosis. Patients and Methods: Twenty patients who underwent radical nephrectomy for RCC were selected for histopathologic study. Normal tissue beneath the neoplasm in 5 specimen was used as control. Nuclear morphometry was carried by using CAS 200 image analysis system. Cellular proliferation was examined by immunohistochemistry, using Ki67 (MIB-I) monoclonal antibody on paraffin embedded tissue. All data were subjected to statistical evaluation. The mean nuclear area was significantly increased versus normal nuclei (ρ=0.0001). It was significant in relation to patients' survival. There was significant increased nuclear area with advancing stages (means =51.85±14.3 μm2, 75.50±12.8 μm2 and 116.35±7.16 μm2) and grade III tumors (mean = 116.27±7.08 μm2). There was an insignificant difference between grades I and II (59.96±17.16 μm2 and 62.34±20.22 μm2 respectively). The mean nuclear diameter was significantly increased with stage IIIa while no difference was noticed between stage I and II (20.29 ± 0.92 μm, 14.31±2.44 μm and 13.33±1.54 μm respectively). Tumor grading was significant in relation to the mean nuclear diameter (14.3±2.44 μm, 15.33 ±1.45 μm and 20.29±0.92 μm). The mean Ki67 (MIBI) proliferative index (PI) was significantly increased in the tumor versus control region (ρ=0.0001). Ki 67 PI was significant in relation to stage (9. 8.89%, 45.98±4.43% and 58.67±6.23%), (ρ=0.0001). However, PI was significantly increased with grade III tumors without a significant difference between grade I and II (ρ=0.02). Morphometric nuclear area and Ki67 proliferation index could provide reliable information that complements the other parameter to assess

  2. 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

  3. Anti-Proliferative Effect of Rosmarinus officinalis L. Extract on Human Melanoma A375 Cells.

    Directory of Open Access Journals (Sweden)

    Lucia Cattaneo

    Full Text Available Rosemary (Rosmarinus officinalis L. has been used since ancient times in traditional medicine, while nowadays various rosemary formulations are increasingly exploited by alternative medicine to cure or prevent a wide range of health disorders. Rosemary's bioproperties have prompted scientific investigation, which allowed us to ascertain antioxidant, anti-inflammatory, cytostatic, and cytotoxic activities of crude extracts or of pure components. Although there is a growing body of experimental work, information about rosemary's anticancer properties, such as chemoprotective or anti-proliferative effects on cancer cells, is very poor, especially concerning the mechanism of action. Melanoma is a skin tumor whose diffusion is rapidly increasing in the world and whose malignancy is reinforced by its high resistance to cytotoxic agents; hence the availability of new cytotoxic drugs would be very helpful to improve melanoma prognosis. Here we report on the effect of a rosemary hydroalcoholic extract on the viability of the human melanoma A375 cell line. Main components of rosemary extract were identified by liquid chromatography coupled to tandem mass spectrometry (LC/ESI-MS/MS and the effect of the crude extract or of pure components on the proliferation of cancer cells was tested by MTT and Trypan blue assays. The effect on cell cycle was investigated by using flow cytometry, and the alteration of the cellular redox state was evaluated by intracellular ROS levels and protein carbonylation analysis. Furthermore, in order to get information about the molecular mechanisms of cytotoxicity, a comparative proteomic investigation was performed.

  4. Cucumarioside A2-2 causes changes in the morphology and proliferative activity in mouse spleen.

    Science.gov (United States)

    Pislyagin, E A; Manzhulo, I V; Dmitrenok, P S; Aminin, D L

    2016-05-01

    The immunomodulatory effect of triterpene glycoside cucumarioside A2-2 (CA2-2), isolated from the Far Eastern sea cucumber Cucumaria japonica, on the mouse spleen was investigated in comparison with lipopolysaccharide (LPS). It has been shown that the intraperitoneal (i.p.) glycoside administration did not influence on splenic weights, while the statistically significant increase in splenic weight was observed after LPS administration. Changes in the ratio of red to white pulp after CA2-2 or LPS administration were observed. The proportion of splenic white pulp after glycoside or LPS administration increased by up to 34% and 36%, respectively. A detailed study of the distribution of the РСNA (Proliferating Cell Nuclear Antigen) marker showed that the proliferative activity in the white pulp under CA2-2 and LPS influence increased 2.07 and 2.24 times, respectively. The localization of PCNA-positive nuclei in the white pulp region, as well as their dimensional characteristics, suggests that a large proportion of the proliferating cell population consisted of B cells. The mass spectrometry profiles of spleen peptide/protein homogenate were obtained using the MALDI-TOF-MS (Matrix -Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry) approach. It was found that i.p. stimulation of animals with CA2-2 or LPS leads to marked changes in the intensity of revealed characteristic peaks of peptides/proteins after exposure to immunostimulants. PMID:27079859

  5. Arsenite and insulin exhibit opposing effects on epidermal growth factor receptor and keratinocyte proliferative potential

    International Nuclear Information System (INIS)

    Previous work has suggested that arsenic exposure contributes to skin carcinogenesis by preserving the proliferative potential of human epidermal keratinocytes, thereby slowing the exit of putative target stem cells into the differentiation pathway. To find a molecular basis for this action, present work has explored the influence of arsenite on keratinocyte responses to epidermal growth factor (EGF). The ability of cultured keratinocytes to found colonies upon passaging several days after confluence was preserved by arsenite and EGF in an additive fashion, but neither was effective when the receptor tyrosine kinase activity was inhibited. Arsenite prevented the loss of EGF receptor protein and phosphorylation of tyrosine 1173, preserving its capability to signal. The level of nuclear β-catenin was higher in cells treated with arsenite and EGF in parallel to elevated colony forming ability, and expression of a dominant negative β-catenin suppressed the increase in both colony forming ability and yield of putative stem cells induced by arsenite and EGF. As judged by expression of three genes regulated by β-catenin, this transcription factor had substantially higher activity in the arsenite/EGF-treated cells. Trivalent antimony exhibited the same effects as arsenite. A novel finding is that insulin in the medium induced the loss of EGF receptor protein, which was largely prevented by arsenite exposure

  6. Molecular characterisation of Atlantic salmon paramyxovirus (ASPV): A novel paramyxovirus associated with proliferative gill inflammation

    Science.gov (United States)

    Falk, K.; Batts, W.N.; Kvellestad, A.; Kurath, G.; Wiik-Nielsen, J.; Winton, J.R.

    2008-01-01

    Atlantic salmon paramyxovirus (ASPV) was isolated in 1995 from gills of farmed Atlantic salmon suffering from proliferative gill inflammation. The complete genome sequence of ASPV was determined, revealing a genome 16,968 nucleotides in length consisting of six non-overlapping genes coding for the nucleo- (N), phospho- (P), matrix- (M), fusion- (F), haemagglutinin-neuraminidase- (HN) and large polymerase (L) proteins in the order 3???-N-P-M-F-HN-L-5???. The various conserved features related to virus replication found in most paramyxoviruses were also found in ASPV. These include: conserved and complementary leader and trailer sequences, tri-nucleotide intergenic regions and highly conserved transcription start and stop signal sequences. The P gene expression strategy of ASPV was like that of the respiro-, morbilli- and henipaviruses, which express the P and C proteins from the primary transcript and edit a portion of the mRNA to encode V and W proteins. Sequence similarities among various features related to virus replication, pairwise comparisons of all deduced ASPV protein sequences with homologous regions from other members of the family Paramyxoviridae, and phylogenetic analyses of these amino acid sequences suggested that ASPV was a novel member of the sub-family Paramyxovirinae, most closely related to the respiroviruses. ?? 2008 Elsevier B.V. All rights reserved.

  7. Anti-proliferative effects of Bifidobacterium adolescentis SPM0212 extract on human colon cancer cell lines

    International Nuclear Information System (INIS)

    Lactic acid bacteria (LAB) are beneficial probiotic organisms that contribute to improved nutrition, microbial balance, and immuno-enhancement of the intestinal tract, as well as anti-tumor activity. The aim of the present work was to study the growth inhibition of tumor cells by butanol extract of Bifidobacterium adolescentis isolated from healthy young Koreans. The anti-proliferative activity of B. adolescentis isolates was assessed by XTT assays on three human colon cancer cell lines (Caco-2, HT-29, and SW480). The effects of B. adolescentis SPM0212 butanol extract on tumor necrosis factor-α (TNF-α) and nitric oxide (NO) production were tested using the murine macrophage RAW 264.7 cell line. The butanol extract of B. adolescentis SPM0212 dose-dependently inhibited the growth of Caco-2, HT-29, and SW480 cells by 70%, 30%, and 40%, respectively, at 200 μg/mL. Additionally, the butanol extract of B. adolescentis SPM0212 induced macrophage activation and significantly increased the production of TNF-α and NO, which regulate immune modulation and are cytotoxic to tumor cells. The butanol extract of B. adolescentis SPM0212 increased activity of the host immune system and may improve human health by helping to prevent colon cancer as a biological response modifier

  8. Nonproliferative and proliferative lesions of the rat and mouse female reproductive system.

    Science.gov (United States)

    Dixon, Darlene; Alison, Roger; Bach, Ute; Colman, Karyn; Foley, George L; Harleman, Johannes H; Haworth, Richard; Herbert, Ronald; Heuser, Anke; Long, Gerald; Mirsky, Michael; Regan, Karen; Van Esch, Eric; Westwood, F Russell; Vidal, Justin; Yoshida, Midori

    2014-01-01

    The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) Project (www.toxpath.org/inhand.asp) is a joint initiative of the Societies of Toxicological Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP) and North America (STP) to develop an internationally accepted nomenclature for proliferative and nonproliferative lesions in laboratory animals. The purpose of this publication is to provide a standardized nomenclature for classifying microscopic lesions observed in the female reproductive tract of laboratory rats and mice, with color photomicrographs illustrating examples of some lesions. The standardized nomenclature presented in this document is also available electronically on the internet (http://www.goreni.org/). Sources of material included histopathology databases from government, academia, and industrial laboratories throughout the world. Content includes spontaneous and aging lesions as well as lesions induced by exposure to test materials. There is also a section on normal cyclical changes observed in the ovary, uterus, cervix and vagina to compare normal physiological changes with pathological lesions. A widely accepted and utilized international harmonization of nomenclature for female reproductive tract lesions in laboratory animals will decrease confusion among regulatory and scientific research organizations in different countries and provide a common language to increase and enrich international exchanges of information among toxicologists and pathologists. PMID:25516636

  9. Anti-Proliferative Effect of Rosmarinus officinalis L. Extract on Human Melanoma A375 Cells.

    Science.gov (United States)

    Cattaneo, Lucia; Cicconi, Rosella; Mignogna, Giuseppina; Giorgi, Alessandra; Mattei, Maurizio; Graziani, Giulia; Ferracane, Rosalia; Grosso, Alessandro; Aducci, Patrizia; Schininà, M Eugenia; Marra, Mauro

    2015-01-01

    Rosemary (Rosmarinus officinalis L.) has been used since ancient times in traditional medicine, while nowadays various rosemary formulations are increasingly exploited by alternative medicine to cure or prevent a wide range of health disorders. Rosemary's bioproperties have prompted scientific investigation, which allowed us to ascertain antioxidant, anti-inflammatory, cytostatic, and cytotoxic activities of crude extracts or of pure components. Although there is a growing body of experimental work, information about rosemary's anticancer properties, such as chemoprotective or anti-proliferative effects on cancer cells, is very poor, especially concerning the mechanism of action. Melanoma is a skin tumor whose diffusion is rapidly increasing in the world and whose malignancy is reinforced by its high resistance to cytotoxic agents; hence the availability of new cytotoxic drugs would be very helpful to improve melanoma prognosis. Here we report on the effect of a rosemary hydroalcoholic extract on the viability of the human melanoma A375 cell line. Main components of rosemary extract were identified by liquid chromatography coupled to tandem mass spectrometry (LC/ESI-MS/MS) and the effect of the crude extract or of pure components on the proliferation of cancer cells was tested by MTT and Trypan blue assays. The effect on cell cycle was investigated by using flow cytometry, and the alteration of the cellular redox state was evaluated by intracellular ROS levels and protein carbonylation analysis. Furthermore, in order to get information about the molecular mechanisms of cytotoxicity, a comparative proteomic investigation was performed. PMID:26176704

  10. Macular Edema Formation and Deterioration of Retinal Function after Intravitreal Bevacizumab Injection for Proliferative Diabetic Retinopathy

    Directory of Open Access Journals (Sweden)

    Hisanori Imai

    2011-09-01

    Full Text Available Purpose: To report a case of proliferative diabetic retinopathy (PDR showing transient macular edema (ME and deteriorated retinal function after intravitreal bevacizumab injection (IVB. Methods and Results: A 53-year-old man received IVB (1.25 mg/0.05 ml in both eyes for the treatment of PDR. There was no treatment-related complication. However, he complained of photopsia in both eyes 6 h after the injection. Slit-lamp examination revealed mild cellular infiltrations (1+ in the anterior chamber in both eyes. Optical coherence tomography showed ME formation in the left eye. Both full-field and multifocal electroretinography (ERG revealed the deterioration of all parameters in both eyes compared with pretreatment. The inflammation in the anterior segment and ME disappeared 1 day after the injection. ERG parameters were improved 9 days after the injection, except for the N1 and P1 amplitude of multifocal ERG in the left eye. Conclusion: We propose that patients who undergo IVB should be carefully informed and followed up for possible complications including temporal ME formation and retinal function deterioration.

  11. Proliferative activity of vervet monkey bone marrow-derived adherent cells

    International Nuclear Information System (INIS)

    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

  12. Proliferative cell response to loosening of total hip replacements: a cytofluorographic cell cycle analysis.

    Science.gov (United States)

    Santavirta, S; Pajamäki, J; Eskola, A; Konttinen, Y T; Lindholm, T

    1991-01-01

    Monocyte/macrophages and fibroblasts are the major reactive cells in the periprosthetic connective tissue in a loose totally replaced hip. Monocyte/macrophages are bone-marrow-derived, hematogenous cells, whereas mesenchymal fibroblasts replenish by local proliferation. The cell-cycle-phase frequency distribution therefore reflects the local mitotic fibroblast response to the loose total hip replacement (THR) implant. In 13 patients who underwent revision of a loose THR implant, most of the local cells were in the resting G0/G1 phase (88.1 +/- 6.3%, mean +/- SD), whereas 8.6 +/- 3.7% were in the S phase of the cycle, and 3.4 +/- 2.9% had already reached the G2/M phase. The highest DNA values were recorded in an osteoarthritic patient undergoing revision 4 years after the primary uncemented THR, while the lowest values were observed in a rheumatoid arthritis patient with a loose cemented prosthesis 15 years after the primary operation. The results suggest that the local proliferative fibroblast response in general is uniform and does not seem to depend on the type of prosthesis or the use of cement. The responses in aggressive granulomatous-type loosening and the common type of loosening were similar. PMID:1772725

  13. Microglia from neurogenic and non-neurogenic regions display differential proliferative potential and neuroblast support

    Directory of Open Access Journals (Sweden)

    Gregory Paul Marshall

    2014-07-01

    Full Text Available Microglia isolated from the neurogenic subependymal zone (SEZ and hippocampus (HC are capable of massive in vitro population expansion that is not possible with microglia isolated from non-neurogenic regions. We asked if this regional heterogeneity in microglial proliferative capacity is cell intrinsic, or is conferred by interaction with respective neurogenic or non-neurogenic niches. By combining SEZ and cerebral cortex (CTX primary tissue dissociates to generate heterospatial cultures, we find that exposure to the SEZ environment does not enhance CTX microglia expansion; however, the CTX environment exerts a suppressive effect on SEZ microglia expansion. Furthermore, addition of purified donor SEZ microglia to either CTX- or SEZ-derived cultures suppresses the expansion of host microglia, while the addition of donor CTX microglia enhances the over-all microglia yield. These data suggest that SEZ and CTX microglia possess intrinsic, spatially restricted characteristics that are independent of their in vitro environment, and that they represent unique and functionally distinct populations. Finally, we determined that the repeated supplementation of neurogenic SEZ cultures with expanded SEZ microglia allows for sustained levels of inducible neurogenesis, provided that the ratio of microglia to total cells remains within a fairly narrow range.

  14. Anti-proliferative action of silibinin on human colon adenomatous cancer HT-29 cells

    Directory of Open Access Journals (Sweden)

    Reyhan Akhtar

    2014-02-01

    Full Text Available Background: Silibinin a flavonoid from milk thistle (Silybum marianum exhibit a variety of pharmacological actions, including anti-proliferative and apoptotic activities against various types of cancers in intact animals and cancer cell lines. In the present study, the effect of silibinin on human colon cancer HT-29 cells was studied. Method: Incubations of cells with different silibinin concentrations (0.783-1,600 μg/ml for 24, 48 or 72 h showed a progressive decline in cell viability. Results: Loss of cell viability was time dependent and optimum inhibition of cell growth (78% was observed at 72 h. Under inverted microscope, the dead cells were seen as cell aggregates. IC50 (silibinin concentration killing 50% cells values were 180, 110 and 40μg/ml at 24, 48 and 72 h respectively. Conclusion: These findings re-enforce the anticancer potential of silibinin, as reported earlier for various other cancer cell lines (Ramasamy and Agarwal (2008, Cancer Letters, 269: 352-62.

  15. White kidney bean lectin exerts anti-proliferative and apoptotic effects on cancer cells.

    Science.gov (United States)

    Chan, Yau Sang; Xia, Lixin; Ng, Tzi Bun

    2016-04-01

    A 60-kDa glucosamine binding lectin, white kidney bean lectin (WKBL), was purified from Phaseolus vulgaris cv. white kidney beans, by application of anion exchange chromatography on Q-Sepharose, affinity chromatography on Affi-gel blue gel, and FPLC-size exclusion on Superdex 75. The anti-proliferative activity of WKBL on HONE1 cells and HepG2 cells was stronger than the activity on MCF7 cells and WRL68 cells (IC50 values for a 48-h treatment with WKBL on HONE1 cells: 18.8μM; HepG2 cells: 19.7μM; MCF7 cells: 26.9μM; and WRL68 cells: >80μM). The activity could be reduced by addition of glucosamine, which occupies the binding sites of WKBL, indicating that carbohydrate binding is crucial for the activity. Annexin V-FITC and PI staining, JC-1 staining and Hoechst 33342 staining revealed that apoptosis was induced on WKBL-treated HONE1 cells and HepG2 cells, but not as obviously on MCF7 cells. Cell cycle analysis also showed a slight cell cycle arrest on HONE1 cells after WKBL treatment. Western blotting suggested that WKBL induced apoptosis of HONE1 cells occurred through the extrinsic apoptosis pathway, with detection of increased level of active caspase 3, 8 and 9. PMID:26769089

  16. Chemical analyses of wasp-associated streptomyces bacteria reveal a prolific potential for natural products discovery.

    Directory of Open Access Journals (Sweden)

    Michael Poulsen

    Full Text Available Identifying new sources for small molecule discovery is necessary to help mitigate the continuous emergence of antibiotic-resistance in pathogenic microbes. Recent studies indicate that one potentially rich source of novel natural products is Actinobacterial symbionts associated with social 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 of these isolates identified 11 distinct and structurally diverse secondary metabolites, including a novel polyunsaturated and polyoxygenated macrocyclic lactam, which we name sceliphrolactam. By pairing the 15 Streptomyces strains against a collection of fungi and bacteria, we document their antifungal 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.

  17. Medulloblastoma: evaluation of proliferative index by monoclonal antibody Mib-1, its prognostic correlation and therapeutic implications

    Directory of Open Access Journals (Sweden)

    Ferrari Antonio Fernandes

    2003-01-01

    Full Text Available In the past few years, the monoclonal antibody MIB-1 has been used by researchers in order to retrospectively study paraffin imbibed tumor fragments. The medulloblastoma is the most common malignant central nervous system tumor in childhood. The objectives were: determination of the mean Mib-1 LI value from these patients, as well as the prognostic value of the method.This retrospective study represents an analysis of the cellular proliferation index of posterior fossa medulloblastomas collected from 22 patients at A.C. Camargo Hospital, from January 1990 to December 1999. The histopathological diagnosis was confirmed by H&E and proliferative index (LI was achived with Mib-1 which detects proliferating cells during G1, G2, S and M phases.The results demostrated that the mean Mib-1 was 30,1%, and ranged from 5,2% to 62,0%.In conclusion, this method has prognostic value, has to be used as routine for patients harboring medulloblastomas and the ones who have PI greater than the mean value found in this study, should be treated aggressively.

  18. Identification of Chemokines and Growth Factors in Proliferative Diabetic Retinopathy Vitreous

    Directory of Open Access Journals (Sweden)

    Ying Dai

    2014-01-01

    Full Text Available Associations were investigated between levels of chemokines and growth factors in the vitreous and proliferative diabetic retinopathy (PDR. Enrolled were 58 patients (58 eyes requiring pars plana vitrectomy (PPV, with PDR (n=32, none with traction retinal detachment or not (non-PDR. In the latter, 16 had macular hole (MH and 10 had epiretinal membrane (ERM. With a multiplex bead immunoassay, levels of 11 chemokines and growth factors were measured from the undiluted vitreous sample from each patient. In the non-PDR eyes, the levels of the 11 chemokines and growth factors tested were similar between patients with MH and those with ERM. However, the levels of all 11 were significantly higher in the PDR eyes relative to the non-PDR; CCL17, CCL19, and TGFβ3 were markedly upregulated and have not been investigated in PDR previously. The significantly higher levels of CCL4 and CCL11 in PDR contradict the results of previous reports. Based on Spearman’s nonparametric test, moderate-to-strong correlations were found between VEGF and other mediators. Our results indicate that these chemokines and growth factors could be candidates for research into targeted therapies applied either singly or in combination with anti-VEGF drugs for the treatment of PDR.

  19. Mutations in FLVCR2 are associated with proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome (Fowler syndrome).

    Science.gov (United States)

    Meyer, Esther; Ricketts, Christopher; Morgan, Neil V; Morris, Mark R; Pasha, Shanaz; Tee, Louise J; Rahman, Fatimah; Bazin, Anne; Bessières, Bettina; Déchelotte, Pierre; Yacoubi, Mohamed T; Al-Adnani, Mudher; Marton, Tamas; Tannahill, David; Trembath, Richard C; Fallet-Bianco, Catherine; Cox, Phillip; Williams, Denise; Maher, Eamonn R

    2010-03-12

    Proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome (PVHH), also known as Fowler syndrome, is an autosomal-recessively inherited prenatal lethal disorder characterized by hydranencephaly; brain stem, basal ganglia, and spinal cord diffuse clastic ischemic lesions with calcifications; glomeruloid vasculopathy of the central nervous system and retinal vessels; and a fetal akinesia deformation sequence (FADS) with muscular neurogenic atrophy. To identify the molecular basis for Fowler syndrome, we performed autozygosity mapping studies in three consanguineous families. The results of SNP microarrays and microsatellite marker genotyping demonstrated linkage to chromosome 14q24.3. Direct sequencing of candidate genes within the target interval revealed five different germline mutations in FLVCR2 in five families with Fowler syndrome. FLVCR2 encodes a transmembrane transporter of the major facilitator superfamily (MFS) hypothesized to be involved in regulation of growth, calcium exchange, and homeostasis. This is the first gene to be associated with Fowler syndrome, and this finding provides a basis for further studies to elucidate the pathogenetic mechanisms and phenotypic spectrum of associated disorders. PMID:20206334

  20. Anti-proliferative effects of Bifidobacterium adolescentis SPM0212 extract on human colon cancer cell lines

    Directory of Open Access Journals (Sweden)

    Chung Myung

    2008-10-01

    Full Text Available Abstract Background Lactic acid bacteria (LAB are beneficial probiotic organisms that contribute to improved nutrition, microbial balance, and immuno-enhancement of the intestinal tract, as well as anti-tumor activity. The aim of the present work was to study the growth inhibition of tumor cells by butanol extract of Bifidobacterium adolescentis isolated from healthy young Koreans. Methods The anti-proliferative activity of B. adolescentis isolates was assessed by XTT assays on three human colon cancer cell lines (Caco-2, HT-29, and SW480. The effects of B. adolescentis SPM0212 butanol extract on tumor necrosis factor-α (TNF-α and nitric oxide (NO production were tested using the murine macrophage RAW 264.7 cell line. Results The butanol extract of B. adolescentis SPM0212 dose-dependently inhibited the growth of Caco-2, HT-29, and SW480 cells by 70%, 30%, and 40%, respectively, at 200 μg/mL. Additionally, the butanol extract of B. adolescentis SPM0212 induced macrophage activation and significantly increased the production of TNF-α and NO, which regulate immune modulation and are cytotoxic to tumor cells. Conclusion The butanol extract of B. adolescentis SPM0212 increased activity of the host immune system and may improve human health by helping to prevent colon cancer as a biological response modifier.

  1. 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.

  2. Radiation retinopathy as an experimental model for ischemic proliferative retinopathy and rubeosis iridis

    International Nuclear Information System (INIS)

    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

  3. Estrogen receptor-negative breast ductal carcinoma: clinicopathological features and MIB-1 (Ki-67 proliferative index association.

    Directory of Open Access Journals (Sweden)

    Noorasmaliza Mdpaiman

    Full Text Available Breast cancer estrogen receptor (ER status is one of the strong additional factors in predicting response of patients towards hormonal treatment. The main aim of this study was to assess the morphological characteristics and proliferative activity using MIB-1(Ki-67 of estrogen receptor negative invasive breast ductal carcinoma (NOS type as well as to correlate these features with clinicopathological data. We also aim to study the expression of c-erbB2 in ER negative breast tumors. High proliferative rate (MIB-1 above 20% was observed in 63 (63.6% of 99 ER negative tumors and that these tumors were associated with high expression of c-erbB2 (57.6%. We observed that MIB-1 is a reliable independent prognostic indicator for ER negative infiltrating ductal carcinoma in this study.

  4. Computed tomography-guided bone biopsies for evaluation of proliferative vertebral lesions in two boa constrictors (Boa constrictor imperator).

    Science.gov (United States)

    Di Girolamo, Nicola; Selleri, Paolo; Nardini, Giordano; Corlazzoli, Daniele; Fonti, Paolo; Rossier, Christophe; Della Salda, Leonardo; Schilliger, Lionel; Vignoli, Massimo; Bongiovanni, Laura

    2014-12-01

    Two boa constrictors (Boa constrictor imperator) presented with paresis of the trunk originating cranial to the cloaca. Radiographs were consistent with proliferative bone lesions involving several vertebrae. Computed tomography (CT) demonstrated the presence of lytic/expansile lesions. Computed tomography-guided biopsies of the lesions were performed without complications. Histology was consistent with bacterial osteomyelitis and osteoarthritis. Gram-negative bacteria (Salmonella sp. and Pseudomonas sp.) were isolated from cultures of the biopsies. Medical treatment with specific antibiotics was attempted for several weeks in both cases without clinical or radiographic improvements. The animals were euthanized, and necropsy confirmed the findings observed upon CT. To the authors' knowledge, this is the first report of the use of CT-guided biopsies to evaluate proliferative vertebral lesions in snakes. In the present report, CT-guided biopsies were easily performed, and both histologic and microbiologic results were consistent with the final diagnosis. PMID:25632696

  5. 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

  6. PRISM/PRDM6, a Transcriptional Repressor That Promotes the Proliferative Gene Program in Smooth Muscle Cells

    OpenAIRE

    Davis, Christopher A.; Haberland, Michael; Arnold, Michael A.; Sutherland, Lillian B.; McDonald, Oliver G.; Richardson, James A.; Childs, Geoffrey; Harris, Stephen; Owens, Gary K.; Olson, Eric N.

    2006-01-01

    Smooth muscle cells (SMCs) display remarkable phenotypic diversity and plasticity and can readily switch between proliferative and differentiated states in response to extracellular cues. In an effort to identify novel transcriptional regulators of smooth muscle phenotypes, we compared the gene expression profiles of arterial and venous SMCs by microarray-based transcriptional profiling. Among numerous genes displaying distinct expression patterns in these two SMC types, we discovered an expr...

  7. Evaluation of the Anti-proliferative Effects of Ophiocoma erinaceus Methanol Extract Against Human Cervical Cancer Cells

    OpenAIRE

    Baharara, Javad; Amini, Elaheh; Namvar, Farideh

    2016-01-01

    Background: Marine organisms provide appreciable source of novel bioactive compounds with pharmacological potential. There is little information in correlation with anti-cancer activities of brittle star. In the present study, anti-neoplastic efficacy of Ophiocoma erinaceus methanol extract against human cervical cancer cells was investigated. Methods: The HeLa cells were cultured and exposed to brittle star methanol extract for 24 and 48 hr. The anti-proliferative properties were examined by...

  8. Estrogen Receptor-Negative Breast Ductal Carcinoma: Clinicopathological Features and Mib-1 (Ki-67) Proliferative Index Association

    OpenAIRE

    Noorasmaliza Mdpaiman; Siti Aishah Md Ali; Reena Mdzin; Meor Zamari Meor Kamal; Wan Anna Md Amin; Mohan Nallusamy; Pavitratha Puspanathan; Rohaizak Muhammad; Sharifa Ezat Wan Puteh; Srijit Das

    2014-01-01

    Breast cancer estrogen receptor (ER) status is one of the strong additional factors in predicting response of patients towards hormonal treatment. The main aim of this study was to assess the morphological characteristics and proliferative activity using MIB-1(Ki-67) of estrogen receptor negative invasive breast ductal carcinoma (NOS type) as well as to correlate these features with clinicopathological data. We also aim to study the expression of c-erbB2 in ER negative breast tumors. High pro...

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

    International Nuclear Information System (INIS)

    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.)

  10. Valved versus nonvalved cannula small-gauge pars plana vitrectomy for repair of retinal detachments with Grade C proliferative vitreoretinopathy

    OpenAIRE

    Oellers P; Stinnett S; Hahn P

    2016-01-01

    Patrick Oellers, Sandra Stinnett, Paul Hahn Duke Eye Center, Duke University School of Medicine, Durham, NC, USA Purpose: Valved cannulas are a recent addition to small-gauge pars plana vitrectomy (PPV) and provide stable intraocular fluidics. The goal of this study was to compare outcomes and postoperative complication rates of valved vs nonvalved cannula small-gauge PPV for repair of retinal detachments (RDs) complicated by Grade C proliferative vitreoretinopathy (PVR).Methods: A retrospe...

  11. Wound sealing-related complications of 25-gauge vitrectomy in proliferative diabetic retinopathy versus simple macular pathology

    OpenAIRE

    Khulood, M.Sayed; Naito, Takeshi; Mahmoud, M. Farouk; Nagasawa, Toshihiko; Katome, Takashi; Mitamura, Yoshinori; 香留, 崇; 三田村, 佳典

    2011-01-01

    Purpose : To compare the incidence of wound sealing-related complications of 25-gauge transconjunctival sutureless vitrectomy (25-G TSV) for proliferative diabetic retinopathy (PDR) versus non-diabetic simple macular pathology (SMP). Methods : A retrospective comparative study was conducted on 377 eyes that underwent 25-G TSV for PDR (n=189 eyes) or non-diabetic SMP (n=188 eyes). Both groups were compared retrospectively and followed for at least 1 month (range 1-6 months). Mai...

  12. Faster recovery after 25-gauge microincision vitrectomy surgery than after 20-gauge vitrectomy in patients with proliferative diabetic retinopathy

    OpenAIRE

    Ikeda T; Bando H; Emi K; Sato T

    2012-01-01

    Tatsuhiko Sato, Kazuyuki Emi, Hajime Bando, Toshihide IkedaOsaka Rosai Hospital Clinical Research Center for Occupational Sensory Organ Disability, Sakai, JapanBackground and methods: We compared surgical procedures and outcomes, including duration of recovery period, in eyes with proliferative diabetic retinopathy that underwent 25-gauge microincision vitrectomy surgery with those that underwent 20-gauge vitrectomy. Seventy-two eyes from 53 patients that underwent 20-gauge vitrectomy in 2006...

  13. Anatomic and functional outcomes of 25-gauge vitrectomy for repair of eyes with rhegmatogenous retinal detachment complicated by proliferative vitreoretinopathy

    OpenAIRE

    Iwahashi-Shima C; Sato T; Bando H; Ikeda T; Emi K

    2013-01-01

    Chiharu Iwahashi-Shima, Tatsuhiko Sato, Hajime Bando, Toshihide Ikeda, Kazuyuki EmiOsaka Rosai Hospital Clinical Research Center for Occupational Sensory Organ Disability, Sakai, JapanBackground: The purpose of this study was to evaluate the outcome of 25-gauge vitrectomy for repair of rhegmatogenous retinal detachment (RRD) complicated by proliferative vitreoretinopathy (PVR).Methods: Twenty-seven eyes of 27 patients who had undergone 25-gauge vitrectomy for grade C PVR were investigated ret...

  14. One-Pot Ugi/Aza-Michael Synthesis of Highly Substituted 2,5-Diketopiperazines with Anti-Proliferative Properties

    OpenAIRE

    Ulrike Holzgrabe; Gessner, Viktoria H.; Florian Seufert; Carsten Berges; Andreas Hartung

    2012-01-01

    The well-known Ugi reaction of aldehydes with amines, carboxylic acids and isocyanides leads to the formation of acyclic α-acylaminocarboxamides. Replacement of the carboxylic acid derivatives with β-acyl substituted acrylic acids gives access to highly substituted 2,5-diketopiperazines in one single reaction-step without additives or complex reaction procedures. The obtained diketopiperazines show anti-proliferative effects on activated T cells and represent therefore poten...

  15. Progression of nuclear sclerosis based on changes in refractive values after lens-sparing vitrectomy in proliferative diabetic retinopathy

    OpenAIRE

    Ikeda, Tsunehiko

    2014-01-01

    Tsunehiko Ikeda,1 Masahiro Minami,1 Kimitoshi Nakamura,2 Teruyo Kida,1 Masanori Fukumoto,1 Takaki Sato,1 Eisuke Ishizaki11Department of Ophthalmology, Osaka Medical College, Osaka, Japan; 2Nakamura Eye Clinic, Nagano, JapanBackground: Nuclear sclerosis (NS) based on the Emery–Little classification and refractive values after lens-sparing vitrectomy was compared between proliferative diabetic retinopathy (DR) patients and nondiabetic patients.Methods: Progression of NS based on the E...

  16. Influence of constant, alternating and cyclotron low-intensity electromagnetic fields on fibroblast proliferative activity in vitro

    OpenAIRE

    Afinogenov, Gennadi; Afinogenova, Anna; Kalinin, Andrey

    2009-01-01

    Available data allow assuming the presence of stimulation of reparative processes under influence of low-intensity electromagnetic field, commensurable with a magnetic field of the Earth. Research of effects of low-intensity electromagnetic fields on fibroblast proliferative activity in human lungs in cell culture was performed. The influence of a constant electromagnetic field, an alternating electromagnetic field by frequency of 50 Hz and cyclotron electromagnetic field with identical inten...

  17. Influence of constant, alternating and cyclotron low-intensity electromagnetic fields on fibroblast proliferative activity in vitro

    OpenAIRE

    Afinogenov, G; Afinogenova, A; Kalinin, A.

    2009-01-01

    Available data allow assuming the presence of stimulation of reparative processes under influence of low-intensity electromagnetic field, commensurable with a magnetic field of the Earth. Research of effects of low-intensity electromagnetic fields on fibroblast proliferative activity in human lungs in cell culture was performed. The influence of a constant electromagnetic field, an alternating electromagnetic field by frequency of 50 Hz and cyclotron electromagnetic field with identical ...

  18. A useful immunohistochemical approach to evaluate intraductal proliferative lesions of the breast and to predict their prognosis

    OpenAIRE

    Omi, Yoko; Yamamoto, Tomoko; Okamoto, Takahiro; Obara, Takao; KOBAYASHI, MAKIO

    2011-01-01

    An examination was performed on 16 intraductal proliferative breast lesions diagnosed as intraductal papillomas (IP) or usual ductal hyperplasia (UDH), which were followed up for more than 3 years. An immunohistochemical marker panel combining myoepithelial markers, high-molecular-weight keratin (HMWK) and neuroendocrine markers was used. Two of 11 IP cases were re-evaluated as atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS). These cases develo...

  19. Improved anti-proliferative effect of doxorubicin-containing polymer nanoparticles upon surface modification with cationic groups

    OpenAIRE

    Krovi, Sai Archana; Swindell, Elden P.; O’Halloran, Thomas V.; Nguyen, SonBinh T.

    2012-01-01

    Polymer nanoparticles (PNPs) possessing a high density of drug payload have been successfully stabilized against aggregation in biological buffers after amine modification, which renders these PNPs positively charged. The resulting charge-stabilized PNPs retain their original narrow particle size distributions and well-defined spherical morphologies. This stabilization allows these PNPs to have an improved anti-proliferative effect on MDA-MB-231-Br human breast cancer cells compared to non-fu...

  20. Unsupervised lineage-based characterization of primate precursors reveals high proliferative and morphological diversity in the OSVZ

    OpenAIRE

    Pfeiffer, Michael; Betizeau, Marion; Waltispurger, Julie; Pfister, Sabina Sara; Douglas, Rodney J.; Kennedy, Henry; Dehay, Colette

    2016-01-01

    Generation of the primate cortex is characterized by the diversity of cortical precursors and the complexity of their lineage relationships. Recent studies have reported miscellaneous precursor types based on observer classification of cell biology features including morphology, stemness, and proliferative behavior. Here we use an unsupervised machine learning method for Hidden Markov Trees (HMTs), which can be applied to large datasets to classify precursors on the basis of morphology, cell-...

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

    OpenAIRE

    Fabiana Caroline daSilva; Cleto Mariosvaldo Piazzetta; Cassius Carvalho Torres-Pereira; Juliana Lucena Schussel; José Miguel Amenábar

    2016-01-01

    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 ...

  2. Murine regulatory T cells contain hyper-proliferative and death-prone subsets with differential ICOS expression

    OpenAIRE

    Chen, Yong; Shen, Shudan; Gorentla, Balachandra; Gao, Jimin; Zhong, Xiao-Ping

    2012-01-01

    Regulatory T cells (Treg) are crucial for self-tolerance. It has been an enigma that Treg exhibit an anergic phenotype reflected by hypo-proliferation in vitro following T cell receptor (TCR) stimulation but undergo vigorous proliferation in vivo. We report here that, different from conventional T cells (Tcon), murine Treg are prone to death but hyper-proliferative in vitro and in vivo. During in vitro culture, most Treg die with or without TCR stimulation, correlated with constitutive activa...

  3. Relationship between vitreous and serum vascular endothelial growth factor levels, control of diabetes and microalbuminuria in proliferative diabetic retinopathy

    OpenAIRE

    Baharivand, Nader; Zarghami, Nosratollah; Panahi, Farid; Dokht Ghafari, M Yazdan; Fard, Ali Mahdavi; Mohajeri, Abbas

    2012-01-01

    Background Diabetic retinopathy is a serious microvascular disorder of the retina. Vascular endothelial growth factor (VEGF) expression, induced by high glucose levels and hypoxia, is a main feature in retinopathy. The aim of this study was to evaluate the relationship between vitreous and serum VEGF levels and control of diabetes and microalbuminuria in patients with proliferative diabetic retinopathy. Methods Sixty-five patients were enrolled in this case-control study, comprising 30 patien...

  4. Phytochemical Properties and Anti-Proliferative Activity of Olea europaea L. Leaf Extracts against Pancreatic Cancer Cells

    Directory of Open Access Journals (Sweden)

    Chloe D. Goldsmith

    2015-07-01

    Full Text Available 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.

  5. Proliferative response of human prostate cancer cell to hormone inhibited by androgen receptor antisense RNA

    Institute of Scientific and Technical Information of China (English)

    江军; 王洛夫; 方玉华; 靳风烁; 靳文生

    2004-01-01

    Background The failure of endocrine treatment for advanced prostate cancer might be related to aberrant activation of androgen receptor (AR). Prostate cancer cell line LNCaP contains AR that can be activated by androgen, estrogen and progesterone. This study was set to investigate the effects of antisense AR RNA on growth of LNCaP cultured in medium containing varied concentrations of R1881, 17β-estradiol, and progesterone, respectively. Methods LNCaP cells transfected with antisense AR RNA retroviral vector pL-AR-SN were designated as LNCaPas-AR. LNCaP cells containing empty vector pLXSN served as LNCaPNeo. LNCaP and LNCaPNeo were taken as controls. In vitro cell growth assay, proliferative cells of LNCaP and tranfected LNCaPs were counted by typan staining when they cultured with synthetic androgen R1881, 17β-estradiol, and progesterone, respectively. Results Growth of LNCaPas-AR was inhibited significantly (P<0.05) compared with that of LNCaP and LNCaPNeo at 1 nmol/L R1881, 10 nmol/L 17β-estradiol, and 1 nmol/L progesterone, respectively. No difference was seen between LNCaP and LNCaPNeo(P>0.05). Microscopic observation showed that LNCaP and LNCaPNeo cells grew well, but only few LNCaPas-AR cells were alive. Conclusions Our observations indicate that antisense AR RNA retroviral vector pL-AR-SN could change androgen-independent characteristics of LNCaP cells, which might shed some novel insights into the treatment of androgen-independent prostate cancer.

  6. Expression and localisation of BDNF, NT4 and TrkB in proliferative vitreoretinopathy.

    Science.gov (United States)

    Ghazi-Nouri, Seyed M S; Ellis, James S; Moss, Stephen; Limb, G Astrid; Charteris, David G

    2008-05-01

    Exogenous brain derived neurotrophic factor (BDNF) is known to rescue ganglion cell death after optic nerve injury. Its mechanism of action is believed to be indirect via glial cells in the retina. In this study we investigated the changes in expression and localisation of BDNF, neurotrophin-4 (NT4) and their common receptor (TrkB) in retinectomy sections of patients with proliferative vitreoretinopathy (PVR). Nine full-thickness retinectomy specimens obtained at retinal reattachment surgery for PVR were fixed in 4% paraformaldehyde immediately after excision and compared to similarly processed normal donor retinas (4 eyes). Agarose-embedded sections (100 microm thick) were double labelled for immunohistochemistry by confocal microscopy, with antibodies against BDNF, NT4, TrkB, rod opsin, glial fibrillary acidic protein (GFAP), cellular retinaldehyde binding protein (CRALBP) and Brn3. This study demonstrates expression of NT4 by ganglion cells and shows expression of BDNF and NT4 in the outer photoreceptor segments is downregulated during PVR, whilst NT4 is markedly upregulated throughout the retina during this condition. The findings here suggest that NT4 may play a neural protective role during the development of PVR. It also shows that upregulation of NT4 in PVR is localised to Müller glial cells, indicating either over-expression of this factor by Müller cells or that Müller cells internalise NT4 for trafficking across the retina. TrkB expression was not observed in PVR retina. The observations that Müller glia demonstrate upregulation of NT4 suggests that retinal injury may lead to activation of this neurotrophin by Müller cells as part of their neuroprotective functions. PMID:18405896

  7. Binding, Antioxidant and Anti-proliferative Properties of Bioactive Compounds of Sweet Paprika (Capsicum annuum L.).

    Science.gov (United States)

    Kim, Hong-Gi; Bae, Jong-Hyang; Jastrzebski, Zenon; Cherkas, Andriy; Heo, Buk-Gu; Gorinstein, Shela; Ku, Yang-Gyu

    2016-06-01

    The scope of this research was to determine the bioactive composition, antioxidant, binding, and anti-proliferative properties of red sweet paprika growing under artificial light. The amounts of carotenoids, chlorophyll, polyphenols, tannins, and flavonoids in red paprika (RP), cultivated in Korea, before and after light treatments under high pressure sodium (HPS) and lighting emitting plasma (LEP) lamps (RPControl, RPHPS, RPLEP), were analyzed in water (W) and ethanolic extracts (Et). Spectroscopic, radical scavenging assays, fluorescence and cytotoxicity measurements were applied. The results of this study showed that total chlorophyll and carotenes were the highest in RPHPS (10.50 ± 1.02 and 33.90 ± 3.26 μg/g dry weight (DW)). The strongest antioxidant capacity (μM TE/g DW) in a 2, 2'-azino-bis (3-ethyl-benzothiazoline-6-sulfonic acid) diammonium salt (ABTS(•+)) assay was in RPControlEt (24.34 ± 2.36), in a ferric-reducing/antioxidant power (FRAP) assay in RPHPSW (27.08 ± 2.4) and in a cupric reducing antioxidant (CUPRAC) in RPLEPW (70.99 ± 7.11). The paprika ethanolic extracts showed lower values in their bioactivity than the water ones. The binding and cytotoxicity abilities of extracted polyphenols correlated with their amounts. LEP treatment is better for plant growth characteristics than other conventional treatments. The investigated paprika samples can be used as a source of antioxidants. PMID:27184000

  8. Azithromycin Synergistically Enhances Anti-Proliferative Activity of Vincristine in Cervical and Gastric Cancer Cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Xuezhang; Zhang, Yuyan; Li, Yong; Hao, Xiujing; Liu, Xiaoming, E-mail: erc1080@gmail.com; Wang, Yujiong, E-mail: erc1080@gmail.com [Key Laboratory of the Ministry of Education for the Conservation and Utilization of Special Biological Resources of Western China, Yinchuan 750021, Ningxia (China); College of Life Science, Ningxia University, Yinchuan 750021, Ningxia (China)

    2012-12-04

    In this study, the anti-proliferative and anticancer activity of azithromycin (AZM) was examined. In the presence of AZM, cell growth was inhibited more effectively in Hela and SGC-7901 cancer cells, relative to transformed BHK-21 cells. The respective 50% inhibition of cell growth (IC{sub 50}) values for Hela, SGC-7901 and BHK-21 were 15.66, 26.05 and 91.00 µg/mL at 72 h post incubation, indicative of a selective cytotoxicity against cancer cells. Cell apoptosis analysis using Hoechst nuclear staining and annexin V-FITC binding assay further demonstrated that AZM was capable of inducing apoptosis in both cancer cells and transformed cells. The apoptosis induced by AZM was partly through a caspase-dependent mechanism with an up-regulation of apoptotic protein cleavage PARP and caspase-3 products, as well as a down-regulation of anti-apoptotic proteins, Mcl-1, bcl-2 and bcl-X1. More importantly, a combination of AZM and a low dose of the common anti-cancer chemotherapeutic agent vincristine (VCR), produced a selectively synergistic effect on apoptosis of Hela and SGC-7901 cells, but not BHK-21 cells. In the presence of 12.50 μg/mL of VCR, the respective IC{sub 50} values of Hela, SGC-7901 and BHK-21 cells to AZM were reduced to 9.47 µg/mL, 8.43 µg/mL and 40.15 µg/mL at 72 h after the incubation, suggesting that the cytotoxicity of AZM had a selective anti-cancer effect on cancer over transformed cells in vitro. These results imply that AZM may be a potential anticancer agent for use in chemotherapy regimens, and it may minimize side effects via reduction of dosage and enhancing the effectiveness common chemotherapeutic drugs.

  9. Quantitative nucleic features are effective for discrimination of intraductal proliferative lesions of the breast

    Directory of Open Access Journals (Sweden)

    Masatoshi Yamada

    2016-01-01

    Full Text Available Background: Intraductal proliferative lesions (IDPLs of the breast are recognized as a risk factor for subsequent invasive carcinoma development. Although opportunities for IDPL diagnosis have increased, these lesions are difficult to diagnose correctly, especially atypical ductal hyperplasia (ADH and low-grade ductal carcinoma in situ (LG-DCIS. In order to define the difference between these lesions, many molecular pathological approaches have been performed. However, still we do not have a molecular marker and objective histological index about IDPLs of the breast. Methods: We generated full digital pathology archives from 175 female IDPL patients, including usual ductal hyperplasia (UDH, ADH, LG-DCIS, intermediate-grade (IM-DCIS, and high-grade (HG-DCIS. After total 2,035,807 nucleic segmentations were extracted, we evaluated nuclear features using step-wise linear discriminant analysis (LDA and a support vector machine. Results: High diagnostic accuracy (81.8–99.3% was achieved between pathologists' diagnoses and two-group LDA predictions from nucleic features for IDPL discrimination. Grouping of nuclear features as size and shape-related or intranuclear texture-related revealed that the latter group was more important when distinguishing between normal duct, UDH, ADH, and LG-DCIS. However, these two groups were equally important when discriminating between LG-DCIS and HG-DCIS. The Mahalanobis distances between each group showed that the smallest distance values occurred between LG-DCIS and IM-DCIS and between ADH and Normal. On the other hand, the distance value between ADH and LG-DCIS was larger than this distance. Conclusions: In this study, we have presented a practical and useful digital pathological method that incorporates nuclear morphological and textural features for IDPL prediction. We expect that this novel algorithm is used for the automated diagnosis assisting system for breast cancer.

  10. African Ancestry Analysis and Admixture Genetic Mapping for Proliferative Diabetic Retinopathy in African Americans

    Science.gov (United States)

    Tandon, Arti; Chen, Ching J.; Penman, Alan; Hancock, Heather; James, Maurice; Husain, Deeba; Andreoli, Christopher; Li, Xiaohui; Kuo, Jane Z.; Idowu, Omolola; Riche, Daniel; Papavasilieou, Evangelia; Brauner, Stacey; Smith, Sataria O.; Hoadley, Suzanne; Richardson, Cole; Kieser, Troy; Vazquez, Vanessa; Chi, Cheryl; Fernandez, Marlene; Harden, Maegan; Cotch, Mary Frances; Siscovick, David; Taylor, Herman A.; Wilson, James G.; Reich, David; Wong, Tien Y.; Klein, Ronald; Klein, Barbara E. K.; Rotter, Jerome I.; Patterson, Nick; Sobrin, Lucia

    2015-01-01

    Purpose. To examine the relationship between proportion of African ancestry (PAA) and proliferative diabetic retinopathy (PDR) and to identify genetic loci associated with PDR using admixture mapping in African Americans with type 2 diabetes (T2D). Methods. Between 1993 and 2013, 1440 participants enrolled in four different studies had fundus photographs graded using the Early Treatment Diabetic Retinopathy Study scale. Cases (n = 305) had PDR while controls (n = 1135) had nonproliferative diabetic retinopathy (DR) or no DR. Covariates included diabetes duration, hemoglobin A1C, systolic blood pressure, income, and education. Genotyping was performed on the Affymetrix platform. The association between PAA and PDR was evaluated using logistic regression. Genome-wide admixture scanning was performed using ANCESTRYMAP software. Results. In the univariate analysis, PDR was associated with increased PAA (odds ratio [OR] = 1.36, 95% confidence interval [CI] = 1.16–1.59, P = 0.0002). In multivariate regression adjusting for traditional DR risk factors, income and education, the association between PAA and PDR was attenuated and no longer significant (OR = 1.21, 95% CI = 0.59–2.47, P = 0.61). For the admixture analyses, the maximum genome-wide score was 1.44 on chromosome 1. Conclusions. In this largest study of PDR in African Americans with T2D to date, an association between PAA and PDR is not present after adjustment for clinical, demographic, and socioeconomic factors. No genome-wide significant locus (defined as having a locus-genome statistic > 5) was identified with admixture analysis. Further analyses with even larger sample sizes are needed to definitively assess if any admixture signal for DR is present. PMID:26098467

  11. Increased Stiffness in Aged Skeletal Muscle Impairs Muscle Progenitor Cell Proliferative Activity.

    Directory of Open Access Journals (Sweden)

    Grégory Lacraz

    Full Text Available Skeletal muscle aging is associated with a decreased regenerative potential due to the loss of function of endogenous stem cells or myogenic progenitor cells (MPCs. Aged skeletal muscle is characterized by the deposition of extracellular matrix (ECM, which in turn influences the biomechanical properties of myofibers by increasing their stiffness. Since the stiffness of the MPC microenvironment directly impacts MPC function, we hypothesized that the increase in muscle stiffness that occurs with aging impairs the behavior of MPCs, ultimately leading to a decrease in regenerative potential.We showed that freshly isolated individual myofibers from aged mouse muscles contain fewer MPCs overall than myofibers from adult muscles, with fewer quiescent MPCs and more proliferative and differentiating MPCs. We observed alterations in cultured MPC behavior in aged animals, where the proliferation and differentiation of MPCs were lower and higher, respectively. These alterations were not linked to the intrinsic properties of aged myofibers, as shown by the similar values for the cumulative population-doubling values and fusion indexes. However, atomic force microscopy (AFM indentation experiments revealed a nearly 4-fold increase in the stiffness of the MPC microenvironment. We further showed that the increase in stiffness is associated with alterations to muscle ECM, including the accumulation of collagen, which was correlated with higher hydroxyproline and advanced glycation end-product content. Lastly, we recapitulated the impaired MPC behavior observed in aging using a hydrogel substrate that mimics the stiffness of myofibers.These findings provide novel evidence that the low regenerative potential of aged skeletal muscle is independent of intrinsic MPC properties but is related to the increase in the stiffness of the MPC microenvironment.

  12. Unexpected recovery from longterm renal failure in severe diffuse proliferative lupus nephritis

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    Ross Sophia

    2012-08-01

    Full Text Available Abstract Background Severe renal manifestation of systemic lupus erythematosus (SLE is not uncommon and is associated with an indeterminate prognosis. Complete remission can be obtained, however, at least in the young when chronic lesions are absent and adequate anti-inflammatory therapy is immediately initiated. Case presentation We report the unusual case of a 12-year-old girl who presented with severe oliguric renal failure, macrohematuria and skin rash. Renal biopsy revealed the diagnosis of severe diffuse proliferative glomerulonephritis (GN with cellular crescents in 15 out of 18 glomeruli and full-house pattern in immunofluorescence indicating lupus nephritis IVB according to WHO, IV-G(A according to ISN/RPS classification. The serological parameters confirmed the diagnosis of SLE and the patient was immediately treated with methylprednisolone, cyclophosphamide and immunoadsorption. Initially, despite rapid amelioration of her general condition, no substantial improvement of renal function could be achieved and the patient needed hemodialysis treatment for 12 weeks. Unexpectedly, in the further follow-up at first diuresis increased and thereafter also creatinine levels substantially declined so that hemodialysis could be discontinued. Today, 6 years after the initial presentation, the patient has normal renal function and a SLEDAI score of 0 under a continuous immunosuppressive therapy with Mycophenolate mofetil (MMF and low dose steroid. Conclusion Despite the severity of the initial renal injury and the unfavourable renal prognosis the kidney apparently has a tremendous capacity to recover in young patients when the damage is acute and adequate anti-inflammatory therapy is initiated without delay.

  13. Characterisation of human non-proliferative diabetic retinopathy using the fractal analysis

    Institute of Scientific and Technical Information of China (English)

    Stefan; Tǎlu; Dan; Mihai; Cǎlugǎru; Carmen; Alina; Lupascu

    2015-01-01

    · AIM: To investigate and quantify changes in the branching patterns of the retina vascular network in diabetes using the fractal analysis method.·METHODS: This was a clinic-based prospective study of 172 participants managed at the Ophthalmological Clinic of Cluj-Napoca, Romania, between January 2012 and December 2013. A set of 172 segmented and skeletonized human retinal images, corresponding to both normal(24 images) and pathological(148 images)states of the retina were examined. An automatic unsupervised method for retinal vessel segmentation was applied before fractal analysis. The fractal analyses of the retinal digital images were performed using the fractal analysis software Image J. Statistical analyses were performed for these groups using Microsoft Office Excel2003 and Graph Pad In Stat software.·RESULTS: It was found that subtle changes in the vascular network geometry of the human retina are influenced by diabetic retinopathy(DR) and can be estimated using the fractal geometry. The average of fractal dimensions D for the normal images(segmented and skeletonized versions) is slightly lower than the corresponding values of mild non-proliferative DR(NPDR) images(segmented and skeletonized versions).The average of fractal dimensions D for the normal images(segmented and skeletonized versions) is higher than the corresponding values of moderate NPDR images(segmented and skeletonized versions). The lowestvalues were found for the corresponding values of severe NPDR images(segmented and skeletonized versions).· CONCLUSION: The fractal analysis of fundus photographs may be used for a more complete understanding of the early and basic pathophysiological mechanisms of diabetes. The architecture of the retinal microvasculature in diabetes can be quantitative quantified by means of the fractal dimension.Microvascular abnormalities on retinal imaging may elucidate early mechanistic pathways for microvascular complications and distinguish patients with DR from

  14. Proliferative and Glycolytic Assessment of the Whole-Body Bone Marrow Compartment

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    Mohammed Goryawala

    2015-06-01

    Full Text Available Objective: Quantitative assessment of active bone marrow (BM in vivo is yet to be well-defined. This study aims to compare total body BM volume estimations obtained from use of both18F-FLT PET/CT and 18F-FDG PET/CT in order to consolidate higher cellular proliferation rates with imaging the highly active red BM in pancreatic cancer. Methods: This phase I pilot study includes seven patients with pancreatic cancers who underwent both 18F-FLT and 18F-FDG imaging each acquired within a week’s duration. A CT-based classifier is used for segmenting bone into cortical and trabecular regions. The total BM volume is determined through statistical thresholding on PET activity found within the trabecular bone. Results: Results showed that 18F-FLT measures of red BM volume (RBV were higher than those obtained from 18F-FDG (∆=89.21 ml. RBV obtained using 18F-FLT in males were found to have high correlation with measured weight (R2=0.61 and BMI (R2=0.70. The red BM fraction obtained from 18F-FLT was significantly different between males and females, with females showing much higher red bone matter within the trabecular bone (p<0.05. In contrast to 18F-FLT, 18F-FDG BM measurements showed that RBV was significantly different between males and females (p<0.05. Results also show that spinal activity SUV threshold for red BM segmentation is significantly different between 18F-FLT PET and 18F-FDG PET (p<0.05. Conclusion: By combining 18F-FLT-PET and 18F-FDG-PET, this study provides useful insights for in vivo BM estimation through its proliferative and glycolytic activities

  15. Cigarette smoking and risk of benign proliferative epithelial disorders of the breast

    International Nuclear Information System (INIS)

    Benign proliferative epithelial disorders (BPED) of the breast are conditions which are thought to have premalignant potential. The purpose of the present investigation was to study the association between cigarette smoking and risk of BPED. The study was undertaken within the 56,837 women within Canadian National Breast Screening Study (NBSS) who completed self-administered lifestyle and dietary questionnaires. (The NBSS is a randomized controlled trial of screening for breast cancer in women aged 40-59 at recruitment.) During the course of the follow-up period, a total of 691 women in the dietary cohort were diagnosed with biopsy-confirmed incident BPED. For comparative purposes, a subcohort consisting of a random sample of 5681 women (including 65 of the subjects with BPED) was selected from the full cohort. After exclusions for various reasons, the analyses were based on 691 cases and 5443 non-cases. Overall, the results of the present study are almost uniformly null, and provide little support for an association between cigarette smoking and risk of BPED. Analyses conducted separately in the screened and control arms of the NBSS also failed to provide strong support for associations, and there was little difference between the results for screen-detected and interval-detected BPED. There was some suggestion of an increase in risk in post-menopausal ex-smokers, but the trend in risk with cigarette-years of exposure in this group was not statistically significant. Risk in ex-smokers varied little by years since smoking cessation. There was little evidence for associations with either atypical or non-atypical forms of BPED

  16. Evaluation of cell proliferative activity after irradiation using immunohistochemical approach and flow cytometry

    International Nuclear Information System (INIS)

    To evaluate a proliferative activity of post-irradiated malignant cells, we studied the kinetics of HeLa cells using immunohistochemical approach and flow cytometry. HeLa cells were stained with two proliferation-associated monoclonal antibodies, Ki-67 and anti-DNA polymerase α antibody. Nucleoli of non-irradiated cells were granularly stained with Ki-67. After irradiation, only the center of nuclei was diffusely stained with Ki-67. One hundred forty-four hours after low-dose irradiation, the staining patterns became the same as the control. On the other hand, after high-dose irradiation, the center of nuclei was weakly stained. DNA polymerase α was diffusely labelled with nuclei of the control. It was located around the border of nuclei of low-dose irradiated cells like a ring. But after high-dose irradiation, it was granularly distributed in the periphery of nuclei. FITC conjugated Ki-67/PI two parameter analysis was done by a single laser flow cytometer. Twenty-four hours after irradiation, DNA-histograms showed the accumulation to G2/M phase and the increase of DNA content of G2/M cells, as exposure dose was increased. Two parameter analysis showed the increase of FITC uptake of G2/M phase as dose increased. These changes of flow cytometry were remarkably observed after 24 hours' incubation. It was shown that the difference of Ki-67 antigen and DNA polymerase α appearance depended on the irradiation dose. These findings suggest that immunohistochemical staining with Ki-67 or anti-DNA polymerase α antibody and flow cytometry using Ki-67 are available to evaluate cell damages after irradiation. (author)

  17. Combined pars plana vitrectomy-scleral buckle versus pars plana vitrectomy for proliferative vitreoretinopathy.

    Science.gov (United States)

    Lai, Frank H P; Lo, Ernie C F; Chan, Vesta C K; Brelen, Mårten; Lo, Wai Ling; Young, Alvin L

    2016-04-01

    The purpose of the study is to evaluate the surgical outcomes of combined pars plana vitrectomy-scleral buckle (PPV-SB) versus pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment complicated with proliferative vitreoretinopathy (PVR). One thousand one hundred and seventy four patients with rhegmatogenous retinal detachment surgery between January 2002 and December 2013 were retrospectively reviewed. Patients with grade C PVR treated with either combined PPV-SB or PPV alone were included in the study. Study outcomes included single surgery anatomic success rate and postoperative visual outcome at 12 months postoperatively. Seventy-seven patients with grade C PVR were identified for analysis. At the end of 12-month follow-up, 80.5 % eyes (33/41) in the PPV-SB group and 58.3 % eyes (21/36) in the PPV group achieved single surgery anatomical success. In a multiple logistic regression model, none of the baseline variables (age, gender, macula status, grade of PVR, extent of detachment, presence of vitreous hemorrhage, lens status, status of high myopia) nor types of retinal detachment surgery (use of scleral buckle, barrier endolaser, 360 degree endolaser, cryopexy, retinectomy, tamponade agent, phacoemulsification) had significant effect on single surgery anatomical success. The post-treatment mean logMAR visual acuity of the PPV-SB group was 1.58 ± 0.58 and the PPV group was 1.57 ± 0.61. There was no significant difference in the postoperative visual acuity between the two groups (P = 0.849). For patients with grade C PVR, PPV-SB did not demonstrate a superiority over PPV alone in achieving single surgery anatomical success. PMID:26260357

  18. The kinetics of VEGF and MCP-1 in the second vitrectomy cases with proliferative diabetic retinopathy.

    Science.gov (United States)

    Sassa, Y; Yoshida, S; Ishikawa, K; Asato, R; Ishibashi, T; Kono, T

    2016-05-01

    PurposeTo determine whether the concentrations of vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein (MCP)-1 in the vitreous changed after vitrectomy in patients with proliferative diabetic retinopathy (PDR).ParticipantsTwenty-one eyes of 21 patients who needed a second surgery for PDR were included. The reasons for the second surgery were tractional retinal detachment (TRD), neovascular glaucoma, persistent vitreous hemorrhage, macular pucker, and secondary intraocular lens (IOL) implant.MethodsWe measured the VEGF and MCP-1 levels using sandwich enzyme-linked immunosorbent assays in vitreous samples collected from patients with PDR before pars plana vitrectomy (without IOL implantation), and from the same patients during the second surgery.ResultsThere was not significant change in mean VEGF concentrations when comparing first (0.81±0.88 ng/ml) and second surgeries (1.09±1.51 ng/ml). The MCP-1 level was significantly elevated at the time of second surgery (2.20±2.21 ng/ml) compared with the first vitrectomy (0.72±0.57 ng/ml). The MCP-1 levels of the second surgery cases with TRD (3.18±2.27 ng/ml) increased significantly compared with those with other complications (1.72±2.10 ng/ml).ConclusionsAt the second vitrectomy, VEGF did not change significantly in the vitreous of the patients examined. The MCP-1 concentration was markedly elevated at the second vitrectomy, implying an association between the prolonged inflammation after vitrectomy and complications, especially TRD. PMID:26915745

  19. Stimulative Effects of Low Intensity He-Ne Laser Irradiation on the Proliferative Potential and Cell-Cycle Progression of Myoblasts in Culture

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    Cui-Ping Zhang

    2014-01-01

    Full Text Available Low intensity laser irradiation (LILI was found to promote the regeneration of skeletal muscle in vivo but the cellular mechanisms are not fully understood. Myoblasts, normally quiescent and inactivated in adult skeletal muscle, are a type of myogenic progenitor cells and considered as the major candidates responsible for muscle regeneration. The aim of the present study was to study the effect of LILI on the growth potential and cell-cycle progression of the cultured myoblasts. Primary myoblasts isolated from rat hind legs were cultured in nutrient-deficient medium for 36 hours and then irradiated by helium-neon laser at a certain energy density. Immunohistochemical and flow cytometric analysis revealed that laser irradiation could increase the expression of cellular proliferation marker and the amount of cell subpopulations in the proliferative phase as compared with the nonirradiated control group. Meanwhile, the expressions of cell-cycle regulatory proteins in the laser-treated myoblasts were markedly upregulated as compared to the unirradiated cells, indicating that LILI could promote the reentry of quiescent myoblasts into the cell division cycle. These results suggest that LILI at certain fluences could promote their proliferation, thus contributing to the skeletal muscle regeneration following trauma and myopathic diseases.

  20. Research Progress and Control Measure of Porcine Proliferative Enteritis%猪增生性肠炎研究进展及防控措施

    Institute of Scientific and Technical Information of China (English)

    张兵; 吴发兴; 沈文正; 高睿; 李军辉; 王立强

    2011-01-01

    Lawsonia intracellularis is a strict intracellular asporous bacterium,negative for Gram-staining but positive for acid-fast staining.It mainly infects 3-to 20-week-old pigs and causes "porcine proliferative enteritis" which clinically manifests chronic intermittent or acute hemorrhagic diarrhea with tar-like black feces or bloody feces.Pathological changes show thickened and eminent stratum mucosum in posterior segment of small intestine and anterior segment of colon,and formation of characteristic cladodromous wrinkles.And intensive proliferation of intestinal glandular epithelium resulted in abnormal distribution of kladodromous crypts of lieberkuhn.Porcine proliferative enteritis can be diagnosed according to epidemiology,clinical features,etiology,pathology,serology,molecular biology and clinically needs to be discriminated from swine dysentery,clostridial enteritis of piglet and swine paratyphoid.The control of the disease covers the management of swine population,the introduction of breeding boars,the disinfection,the chemoprophylaxis and the effective vaccination practice.%胞内劳森菌为严格细胞内寄生的无芽孢细菌,革兰氏染色阴性,抗酸染色阳性。主要感染3~20周龄猪而引起"猪增生性肠炎",临床表现慢性间歇性下痢或急性出血性下痢,排焦油样黑色粪便或血便。病理变化为小肠后段和结肠前段肠黏膜层增厚隆起,形成特征性分枝状皱折,肠腺上皮剧烈增生,形成畸形排列的分枝状肠腺。本病可进行流行病学、临床特征、病原学、病理学、血清学、分子生物学诊断,并需要与猪痢疾、猪梭菌性肠炎、仔猪副伤寒等病进行临床鉴别。本病的防控,应从猪群管理、引种、消毒、药物预防等方面考虑,接种疫苗是行之有效的措施。

  1. Risk evaluation of outcome of vitreous surgery for proliferative diabetic retinopathy based on vitreous level of vascular endothelial growth factor and angiotensin II

    OpenAIRE

    Funatsu, H; Yamashita, H; Noma, H; Mimura, T; Sakata, K; Hori, S

    2004-01-01

    Aims: To ascertain whether measurement of the vitreous fluid levels of vascular endothelial growth factor (VEGF) or angiotensin II (Ang II) could predict the outcome of vitreous surgery in patients with proliferative diabetic retinopathy (PDR).

  2. 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

    Directory of Open Access Journals (Sweden)

    Watson Cheryl S

    2009-09-01

    Full Text Available Abstract Background 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, GH3/B6/F10, originally subcloned from GH3 cells based on its ability to express high levels of the membrane estrogen receptor-α. Methods 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. Results Four phytoestrogens (coumestrol, daidzein, genistein, and trans-resveratrol were studied over wide concentration ranges. Except trans-resveratrol, all phytoestrogens increased GH3/B6/F10 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. Conclusion 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

  3. Regulation of VEGF and bFGF mRNA expression and other proliferative compounds in skeletal muscle cells.

    Science.gov (United States)

    Jensen, L; Schjerling, P; Hellsten, Y

    2004-01-01

    The role of muscle contraction, prostanoids, nitric oxide and adenosine in the regulation of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and endothelial cell proliferative compounds in skeletal muscle cell cultures was examined. VEGF and bFGF mRNA, protein release as well as the proliferative effect of extracellular medium was determined in non-stimulated and electro-stimulated rat and human skeletal muscle cells. In rat skeletal muscle cells these aspects were also determined after treatment with inhibitors and/or donors of nitric oxide (NO), prostanoids and adenosine. Electro-stimulation caused an elevation in the VEGF and bFGF mRNA levels of rat muscle cells by 33% and 43% (P < 0.05), respectively, and in human muscle cells VEGF mRNA was elevated by 24%. Medium from electro-stimulated human, but not rat muscle cells induced a 126% higher (P < 0.05) endothelial cell proliferation than medium from non-stimulated cells. Cyclooxygenase inhibition of rat muscle cells induced a 172% increase (P < 0.05) in VEGF mRNA and a 104% increase in the basal VEGF release. Treatment with the NO donor SNAP (0.5 microM) decreased (P < 0.05) VEGF and bFGF mRNA by 42 and 38%, respectively. Medium from SNAP treated muscle cells induced a 45% lower (P < 0.05) proliferation of endothelial cells than control medium. Adenosine enhanced the basal VEGF release from muscle cells by 75% compared to control. The present data demonstrate that contractile activity, NO, adenosine and products of cyclooxygenase regulate the expression of VEGF and bFGF mRNA in skeletal muscle cells and that contractile activity and NO regulate endothelial cell proliferative compounds in muscle extracellular fluid. PMID:15609080

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

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Tao; Meng, Lingjun [Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A and M Health Science Center, Houston, TX 77030 (United States); Tsai, Robert Y.L., E-mail: rtsai@ibt.tamhsc.edu [Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A and M Health Science Center, Houston, TX 77030 (United States)

    2011-10-22

    Highlights: {yields} Strong synergy between mycophenolic acid (MPA) and 5-FU in MDA-MB-231 cells. {yields} Cell type-dependent synergy between MPA and anti-proliferative agents. {yields} The synergy of MPA on 5-FU is recapitulated by RNA polymerase-I inhibition. {yields} 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.

  5. In vitro antimicrobial and anti-proliferative activities of plant extracts from Spathodea campanulata, Ficus bubu, and Carica papaya.

    Science.gov (United States)

    Mbosso Teinkela, Jean Emmanuel; Assob Nguedia, Jules Clément; Meyer, Franck; Vouffo Donfack, Erik; Lenta Ndjakou, Bruno; Ngouela, Silvère; Tsamo, Etienne; Adiogo, Dieudonné; Guy Blaise Azebaze, Anatole; Wintjens, René

    2016-06-01

    Context African medicinal plants represent a prominent source of new active substances. In this context, three plants were selected for biological investigations based on their traditional uses. Objective The antimicrobial and anti-proliferative features of three plants used for medicinal purpose were evaluated. Materials and methods The antimicrobial activities of methanol extracts of Ficus bubu Warb. (Moraceae) stem bark and leaves, of Spathodea campanulata P. Beauv. (Bignoniaceae) flowers, as well as those of Carica papaya Linn. (Caricaceae) latex, were determined using the microbroth dilution method against a set of bacteria and fungi pathogens including: Enterococcus faecalis, Staphylococcus aureus, S. saprophyticus, S. epidermididis, Escherichia coli, Klebsiella pneumonia, Salmonella typhimurium, Candida albicans, and Trichophyton rubrum. The tested concentrations of extracts ranged from 2500.0 to 2.4 μg/mL and MIC values were evaluated after 24 h incubation at 37 °C. Subsequently, MTT assay was used to estimate anti-proliferative activity of these methanol extracts and of F. bubu latex on three human cancer cell lines (U373 glioblastoma, A549 NSCLC, and SKMEL-28 melanoma). Results The methanol extract of F. bubu stem bark exhibited the highest antimicrobial activity against C. albicans with a MIC value of 9.8 μg/mL, while the F. bubu latex and the methanol extract of F. bubu leaves induced significant anti-proliferative activity against lung (IC50 values of 10 and 14 μg/mL, respectively) and glioma (IC50 values of 13 and 16 μg/mL, respectively) cancer cells. Conclusion These results indicate that effective drugs could be derived from the three studied plants. PMID:26799575

  6. Ki-S1, a novel proliferative marker: flow cytometric assessment of staining in human breast carcinoma cells.

    OpenAIRE

    Camplejohn, R. S.; Brock, A.; Barnes, D. M.; Gillett, C; Raikundalia, B.; Kreipe, H.; Parwaresch, M R

    1993-01-01

    There is considerable interest in immunohistochemical markers of proliferation which are suitable for use on routinely fixed clinical material. The novel proliferation-associated antibody Ki-S1 shows promise in this respect. In this study we have: (i) defined the pattern of Ki-S1 labelling relative to the cell cycle phase; (ii) investigated the labelling pattern with Ki-S1 on a human breast cell line (ZR75) under varying proliferative conditions induced by serum deprivation and refeeding; (ii...

  7. Insulin Promotes Proliferative Vitality and Invasive Capability of Pancreatic Cancer Cells via Hypoxia-inducible Factor 1α Pathway

    Institute of Scientific and Technical Information of China (English)

    汪理; 周伟; 勾善淼; 王统玲; 刘涛; 王春友

    2010-01-01

    This study examined whether insulin-stimulated hypoxia-inducible factor 1α(HIF-1α) expression plays a crucial role in promoting the proliferative vitality and invasive capability in human pancreatic cancer cells.PANC-1 cells were divided into three groups:Control group,insulin group and insulin+YC-1(a pharmacological inhibitor of HIF-1α) group in terms of different treatments.Cells in the insulin group or insulin+YC-1 group were treated with insulin(0.1,1,10 and 100 nmol/L) alone or combined with 3-(5'-hydr...

  8. Progression to macula-off tractional retinal detachment after a contralateral intraoperative intravitreal bevacizumab injection for proliferative diabetic retinopathy.

    Science.gov (United States)

    Zlotcavitch, Leonid; Flynn, Harry W; Avery, Robert L; Rachitskaya, Aleksandra

    2015-01-01

    We report a patient with progression to a macula-off tractional retinal detachment in a fellow eye after a contralateral intraoperative intravitreal bevacizumab injection. A 32-year-old diabetic man noted decreased vision in his left eye 1 week following 25 gauge pars plana vitrectomy, gas tamponade, and intraoperative injection of bevacizumab in his right eye. Left eye visual acuity decreased from 20/80 to 20/200, and macula-off tractional retinal detachment was seen on clinical exam and imaging. Progression of tractional retinal detachment associated with proliferative diabetic retinopathy in a fellow eye after a contralateral intraoperative intravitreal bevacizumab injection may occur. PMID:25609907

  9. The big picture of lives saved by abortion on demand: User pays applied to pro-life advocates

    OpenAIRE

    Pope, Robin

    2009-01-01

    Pro-life advocates focus on a single entity, the foetus. Pro-choice advocates focus on another single entity, the pregnant mother. There should also be a third focus, on all people already born – on how a new entrant on average damages (or enhances) the whole community. Communal accounts are needed on births, not only on wars. This third big picture communal focus reveals two things. First, abortion on demand actually was the biggest factor in reducing crimes and associated deaths in the US i...

  10. One-Pot Ugi/Aza-Michael Synthesis of Highly Substituted 2,5-Diketopiperazines with Anti-Proliferative Properties

    Directory of Open Access Journals (Sweden)

    Ulrike Holzgrabe

    2012-12-01

    Full Text Available The well-known Ugi reaction of aldehydes with amines, carboxylic acids and isocyanides leads to the formation of acyclic α-acylaminocarboxamides. Replacement of the carboxylic acid derivatives with β-acyl substituted acrylic acids gives access to highly substituted 2,5-diketopiperazines in one single reaction-step without additives or complex reaction procedures. The obtained diketopiperazines show anti-proliferative effects on activated T cells and represent therefore potential candidates for targeting unwanted T cell-mediated immune responses.

  11. Effect of laser photocoagulation and bevacizumab intravitreal in proliferative diabetic retinopathy: review on biomarkers of oxidative stress

    Directory of Open Access Journals (Sweden)

    Andi A. Victor

    2014-06-01

    Full Text Available Background: This study was aimed to compare the effect of laser photocoagulation (LF, intravitreal bevacizumab (IVB and combined treatments on biomarkers of oxidative stress such as aldehhyde dehidrogenase (ALDH, malondialdehyde (MDA level, superoxide dismutase (SOD activities, and vitreal vascular endothelial growth factor (VEGF on proliferative diabetic retinopathy (DR patients.Methods: In this single blind randomized clinical trial, 72 eyes from 69 cases of proliferative DR in Cipto Mangunkusumo Hospital between February 2011 - June 2013 were randomized into 4 groups : 1 control (n = 18; 2 LF pre-vitrectomy (n = 18; 3 IVB pre-vitrectomy (n = 18; and 4 combined IVB and LF pre-vitrectomy (n = 18. One-way ANOVA was used to compare oxidative stress parameters in the four groups.Results: There were no statistically significant differences in the average plasma ALDH activity (0.034 ± 0.02; 0.027 ± 0.02; 0.025 ± 0.02; 0.031 ± 0.11 IU/mg protein; p = 0.66, vitreal MDA level (1.661 ± 1.21; 1.557 ± 1.32; 1.717 ± 1.54; 1.501 ± 1.09 nmol/mL; p = 0.96 and SOD activity (0.403 ± 0.50; 0.210 ± 0.18; 0.399 ± 0.49; 0.273 ± 0.32 U/mL; p = 0.38 among these four groups, respectively. However, the VEGF vitreal level (pg/mL showed a statistically significant difference (0.356 ± 0.60; 0.393 ± 0.45; 0.150 ± 0.24; 0.069 ± 0.13; p = 0.05. The VEGF level in combination group was five times lower than the control group (p = 0.05.Conclusion: Combined treatments of DR by IVB and LF were correlated with lower vitreal MDA and plasma VEGF level, but did not have any effect on plasma ALDH and vitreal SOD in proliferative DR. Combined treatments with IVB and LF are recommended for the management of proliferative DR patients.  

  12. HIV-mediated immunodepression: in vitro inhibition of T-lymphocyte proliferative response by ultraviolet-inactivated virus

    International Nuclear Information System (INIS)

    In order to assess whether the human retrovirus HIV, like other animal retroviruses, is endowed with intrinsic immunosuppressive activity, we studied the effects of noninfectious, uv-irradiated virus on in vitro lymphocyte function. uvHIV preparations inhibited T-cell proliferation to mitogens and alloantigens, as well as mitogen-driven IL-2 production. The inhibitory effect, which was not exerted by uv-irradiated HTLV-I, was apparently not due to a decrease in cell viability and was likely associated with thermoresistant viral component(s). The suppression proved to be selective for T-cell responses, while sparing other lymphocyte functions, such as the B-cell proliferative response to a selective B-cell mitogen. The inhibitory effect of uvHIV was not counteracted by a substantial reduction in the number of monocytes or by indomethacin. Moreover, IL-1 production by monocytes was not affected upon virus incubation. On the other hand, the proliferative response of both CD4+ and CD8+ T-cell clones was inhibited by uvHIV, suggesting that T cells represent the actual target for the inhibitory effect. Although a sizeable decrease in IL-2 production was observed following uvHIV incubation, exogenous IL-2 was not capable of reversing the virus-induced suppression of the proliferation. The possibility that the immunosuppressive activity of noninfectious HIV contributes to the T-cell defect in infected patients by mechanisms other than the cytopathic effect on CD4+ T lymphocytes is discussed

  13. In vitro antioxidant activities and anti-proliferative properties of the functional herb Abrus cantoniensis and its main alkaloid abrine.

    Science.gov (United States)

    Yang, Mei; Al Zaharna, Mazen; Chen, Yu-Shan; Li, Li; Cheung, Hon-Yeung

    2014-09-01

    Abrus cantoniensis is a common and popular vegetative food consumed as beverage, soup and folk medicine in the tropical and subtropical areas of Asia. It has been claimed valuable for cleansing toxicants in the liver. However, the functional effects of A. cantoniensis have not yet been scientifically explored. This study comprehensively evaluated the in vitro antioxidant and anti-proliferative capacities of the herbal extract and the main alkaloid abrine. Abrine was qualitatively and quantitatively determined in methanol extract (ME) using HPLC-DAD and LC-MS/MS. The results showed that ME, ethyl acetate fraction (EF) and abrine exhibited comparable ABTS radical cation scavenging activities and reducing power to two commercial antioxidants (BHT and Trolox). The EF exerted strong cellular antioxidant activity and selective cytotoxicity against three cancer cell lines in a dose-dependent manner. Biological assays revealed that the EF induced cell cycle arrest at G2/M and apoptosis in MCF-7 and Hep3B cells after 48 h of treatment. Thus, A. cantoniensis exerted potent cellular antioxidant and anti-proliferative properties, highlighting why it has been traditionally used as a functional food. PMID:25059572

  14. Merkel cell polyomavirus and human papilloma virus in proliferative skin lesions arising in patients treated with BRAF inhibitors.

    Science.gov (United States)

    Falchook, G S; Rady, P; Konopinski, J C; Busaidy, N; Hess, K; Hymes, S; Nguyen, H P; Prieto, V G; Bustinza-Linares, E; Lin, Q; Parkhurst, K L; Hong, D S; Sherman, S; Tyring, S K; Kurzrock, R

    2016-07-01

    The potential role of oncogenic viruses mediating development of proliferative skin lesions in patients treated with RAF inhibitors is poorly understood. The objective of this study was to investigate human papilloma virus (HPV) and Merkel cell polyomavirus (MCPyV) in skin lesions among patients treated with RAF inhibitors with the help of a case series describing prevalence of HPV, MCPyV, and RAS mutations in skin biopsies obtained from patients receiving RAF inhibitors and developing cutaneous lesions. HPV-DNA was amplified by PCR utilizing multiple nested primer systems designed for detection of a broad range of HPV types. MCPyV copy number determination with real time PCR technology was performed by a "Quantification of MCPyV, small t region" kit. Thirty-six patients were tested (squamous cell carcinoma (SCC) = 14; verruca vulgaris = 15; other = 11). Nine of 12 SCCs (75 %) and eight of 13 verruca vulgaris lesions (62 %) tested positive for MCPyV whereas none of the normal skin biopsies obtained from nine of these patients tested positive for MCPyV (p = 0.0007). HPV incidence in cutaneous SCCs was not different compared to normal skin (50 vs. 56 %, p = 0.86). The association between MCPyV and proliferative skin lesions after RAF inhibitor therapy merits further investigation. PMID:27098388

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

    International Nuclear Information System (INIS)

    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)

  16. 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.

  17. Classifications for Proliferative Vitreoretinopathy (PVR: An Analysis of Their Use in Publications over the Last 15 Years

    Directory of Open Access Journals (Sweden)

    Salvatore Di Lauro

    2016-01-01

    Full Text Available Purpose. To evaluate the current and suitable use of current proliferative vitreoretinopathy (PVR classifications in clinical publications related to treatment. Methods. A PubMed search was undertaken using the term “proliferative vitreoretinopathy therapy”. Outcome parameters were the reported PVR classification and PVR grades. The way the classifications were used in comparison to the original description was analyzed. Classification errors were also included. It was also noted whether classifications were used for comparison before and after pharmacological or surgical treatment. Results. 138 papers were included. 35 of them (25.4% presented no classification reference or did not use any one. 103 publications (74.6% used a standardized classification. The updated Retina Society Classification, the first Retina Society Classification, and the Silicone Study Classification were cited in 56.3%, 33.9%, and 3.8% papers, respectively. Furthermore, 3 authors (2.9% used modified-customized classifications and 4 (3.8% classification errors were identified. When the updated Retina Society Classification was used, only 10.4% of authors used a full C grade description. Finally, only 2 authors reported PVR grade before and after treatment. Conclusions. Our findings suggest that current classifications are of limited value in clinical practice due to the inconsistent and limited use and that it may be of benefit to produce a revised classification.

  18. Curcumin conjugated with PLGA potentiates sustainability, anti-proliferative activity and apoptosis in human colon carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Bhargav N Waghela

    Full Text Available 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.

  19. Effect of Guibi-Tang, a Traditional Herbal Formula, on Retinal Neovascularization in a Mouse Model of Proliferative Retinopathy

    Directory of Open Access Journals (Sweden)

    Yun Mi Lee

    2015-12-01

    Full Text Available Ocular pathologic angiogenesis is an important causative risk factor of blindness in retinopathy of prematurity, proliferative diabetic retinopathy, and neovascular macular degeneration. Guibi-tang (GBT is a frequently used oriental herbal formula in East Asian countries, and is also called Qui-pi-tang in Chinese and Kihi-To in Japanese. In the present study, we investigated the preventive effect of GBT on retinal pathogenic neovascularization in a mouse model of oxygen-induced retinopathy (OIR. C57BL/6 mice were exposed to 75% hyperoxia for five days on postnatal day 7 (P7. The mice were then exposed to room air from P12 to P17 to induce ischemic proliferative retinopathy. GBT (50 or 100 mg/kg/day was intraperitoneally administered daily for five days (from P12 to P16. On P17, Retinal neovascularization was measured on P17, and the expression levels of 55 angiogenesis-related factors were analyzed using protein arrays. GBT significantly decreased retinal pathogenic angiogenesis in OIR mice, and protein arrays revealed that GBT decreased PAI-1 protein expression levels. Quantitative real-time PCR revealed that GBT reduced vascular endothelial growth factor (VEGF, fibroblast growth factor 2 (FGF2, and plasminogen activator inhibitor 1 (PAI-1 mRNA levels in OIR mice. GBT promotes potent inhibitory activity for retinal neovascularization by decreasing VEGF, FGF2, and PAI-1 levels.

  20. Self-reactive CD4+ T cells and B cells in the blood in health and autoimmune disease: increased frequency of thyroglobulin-reactive cells in Graves' disease

    DEFF Research Database (Denmark)

    Nielsen, Claus H; Moeller, Ane Christine; Hegedüs, Laszlo; Bendtzen, Klaus; Leslie, R Graham Q

    2006-01-01

    (+) T cells and B cells were found in patients with Graves' disease. Notably, both patient groups and healthy controls exhibited higher proliferative responses to thyroglobulin than to a foreign recall antigen, tetanus toxoid. Our results suggest that self-tolerance can be broken by exposure of...

  1. Apoptosis status and proliferative activity in mucopolysaccharidosis type I mice tongue mucosa cells

    OpenAIRE

    Juliana Noguti; Vanessa Gonçalves Pereira; Joice Marques Guilheiro; Ana Maria Martins; Vânia D′Almeida; Daniel Araki Ribeiro

    2012-01-01

    Background: Mucopolysaccharidosis type I (MPS I) is caused by a deficiency of alfa-iduronidase (IDUA), which leads to intralysosomal accumulation of glysosaminoglycans. Evidences point secondary events like oxidative stress on lysosomal storage diseases including MPS I. Patients with MPS I present a wide range of oral clinical manifestations, including tongue hypertrophy, hypertrophyc alveolar process, and carious teeth. However, the mechanisms by which these alterations occur are still not f...

  2. Evaluation of the proliferative activity of immunocompetent cells in the jejunal and iliac lymph nodes of prepubertal female wild boars diagnosed with mixed mycotoxicosis

    Directory of Open Access Journals (Sweden)

    Zielonka Łukasz

    2015-06-01

    Full Text Available The study evaluated the proliferative activity of immunocompetent cells in the jejunal and iliac lymph nodes of prepubertal female wild boars exposed to deoxynivalenol and zearalenone in naturally contaminated feed. The evaluation was performed with the use of the MTT assay and 2 mitogens: lipopolysaccharide (LPS and concanavalin A. Intensified proliferative processes in T and B lymphocytes were revealed. The mitogenic activity of LPS was more expressed in the lymphocytes of both iliac and jejunal lymph nodes in comparison with the control group. Proliferative activity was higher in iliac lymph nodes than in jejunal lymph nodes. A reverse trend was observed in the percentage of live cells, which was higher in jejunal lymph nodes during the evaluation of lymphocyte proliferation.

  3. Automatic detection Non-proliferative Diabetic Retinopathy using image processing techniques

    Directory of Open Access Journals (Sweden)

    RajuS. Maher

    2016-01-01

    Full Text Available Diabetes is a chronic disease that is reaching epidemic proportions worldwide. There are currently more than 190 million people with diabetes worldwide. The World Health Organization (WHO estimates that this will rise to 221 million by the year 2010, largely due to population growth, ageing, urbanization and a sedentary lifestyle. Diabetes is currently the fourth main cause of death in most developed countries. In Singapore, the prevalence of diabetes in our population is 8.2% according to the 2004 National Health Survey. This is expected to grow as our population age. Diabetic Retinopathy, if not well managed and controlled, can progress steadily to devastating complications like blindness. At present, various analyses on complicated interaction between hereditary and environmental factors are being undertaken regarding the onset of diabetes. The development of diabetic complication has become a major concern regarding the prognosis of diabetic patients. Diabetes Retinopathy is one of the most common diseases that people get affected by over the years. By doing this paper, we hope to detect the stages of Diabetic Retinopathy as early as possible so as to prevent and cure more Singaporeans from falling prey to this disease.

  4. A review of infectious gill disease in marine salmonid fish.

    Science.gov (United States)

    Mitchell, S O; Rodger, H D

    2011-06-01

    Infectious gill diseases of marine salmonid fish present a significant challenge in salmon-farming regions. Infectious syndromes or disease conditions affecting marine-farmed salmonids include amoebic gill disease (AGD), proliferative gill inflammation (PGI) and tenacibaculosis. Pathogens involved include parasites, such as Neoparamoeba perurans, bacteria, such as Piscichlamydia salmonis and Tenacibaculum maritimum, and viruses, such as the Atlantic salmon paramyxovirus (ASPV). The present level of understanding of these is reviewed with regard to risk factors, potential impacting factors, methods of best practice to mitigate infectious gill disease, as well as knowledge gaps and avenues for future research. PMID:21401646

  5. Post-infectious glomerulonephritis presenting as acute renal failure in a patient with Lyme disease

    OpenAIRE

    Rolla, Davide; Conti, Novella; Ansaldo, Francesca; Panaro, Laura; Lusenti, Tiziano

    2013-01-01

    Introduction: We report a case of a patient with acute renal failure in Lyme disease-associated focal proliferative mesangial nephropathy. Lyme disease is a vector-borne disease caused by Borrelia burgdorferi, transmitted by the bite of an infected ixodes tick. Post-infectious glomerulonephritis (GN)secondary to Borrelia burgdorferi infection in man could be fatal, as it is in canine Lyme borreliosis. Case: A 61-year old man with chronic ethanolic hepatitis was admitted to a provincial hospit...

  6. 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

  7. ESR1 mutations affect anti-proliferative responses to tamoxifen through enhanced cross-talk with IGF signaling.

    Science.gov (United States)

    Gelsomino, Luca; Gu, Guowei; Rechoum, Yassine; Beyer, Amanda R; Pejerrey, Sasha M; Tsimelzon, Anna; Wang, Tao; Huffman, Kenneth; Ludlow, Andrew; Andò, Sebastiano; Fuqua, Suzanne A W

    2016-06-01

    The purpose of this study was to address the role of ESR1 hormone-binding mutations in breast cancer. Soft agar anchorage-independent growth assay, Western blot, ERE reporter transactivation assay, proximity ligation assay (PLA), coimmunoprecipitation assay, silencing assay, digital droplet PCR (ddPCR), Kaplan-Meier analysis, and statistical analysis. It is now generally accepted that estrogen receptor (ESR1) mutations occur frequently in metastatic breast cancers; however, we do not yet know how to best treat these patients. We have modeled the three most frequent hormone-binding ESR1 (HBD-ESR1) mutations (Y537N, Y537S, and D538G) using stable lentiviral transduction in human breast cancer cell lines. Effects on growth were examined in response to hormonal and targeted agents, and mutation-specific changes were studied using microarray and Western blot analysis. We determined that the HBD-ESR1 mutations alter anti-proliferative effects to tamoxifen (Tam), due to cell-intrinsic changes in activation of the insulin-like growth factor receptor (IGF1R) signaling pathway and levels of PIK3R1/PIK3R3. The selective estrogen receptor degrader, fulvestrant, significantly reduced the anchorage-independent growth of ESR1 mutant-expressing cells, while combination treatments with the mTOR inhibitor everolimus, or an inhibitor blocking IGF1R, and the insulin receptor significantly enhanced anti-proliferative responses. Using digital drop (dd) PCR, we identified mutations at high frequencies ranging from 12 % for Y537N, 5 % for Y537S, and 2 % for D538G in archived primary breast tumors from women treated with adjuvant mono-tamoxifen therapy. The HBD-ESR1 mutations were not associated with recurrence-free or overall survival in response in this patient cohort and suggest that knowledge of other cell-intrinsic factors in combination with ESR1 mutation status will be needed determine anti-proliferative responses to Tam. PMID:27178332

  8. 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

  9. Chemical Composition, Antioxidant, Anti-Inflammatory and Anti-Proliferative Activities of Essential Oils of Plants from Burkina Faso

    Science.gov (United States)

    Bayala, Bagora; Bassole, Imaël Henri Nestor; Gnoula, Charlemagne; Nebie, Roger; Yonli, Albert; Morel, Laurent; Figueredo, Gilles; Nikiema, Jean-Baptiste; Lobaccaro, Jean-Marc A.; Simpore, Jacques

    2014-01-01

    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

  10. 毛细血管内增生性肾炎转变为膜增生性肾炎1例报告%Transition from endocapillary proliferative glomerulonephritis to membrane proliferative glomerulonephritis:a case report

    Institute of Scientific and Technical Information of China (English)

    张宏博; 黄建萍

    2015-01-01

    目的:探讨由毛细血管内增生性肾小球肾炎(EnPGN)转为膜增生性肾小球肾炎(MPGN)的发病机制、诊断要点及治疗。方法回顾性分析1例肾脏病理由EnPGN转为MPGN患儿的临床资料及肾活检病理结果。结果患儿临床表现为蛋白尿及镜下血尿,持续性低补体C3血症,病理类型由EnPGN转为MPGN,经口服激素联合他克莫司治疗后,尿蛋白转阴,补体C3仍低。结论持续补体C3降低的患儿,病理类型可转变,需要早期诊断及时治疗。%ObjectiveTo investigate the mechanism, diagnosis and treatment of membrane proliferative glome-rulo-nephritis (MPGN) transitioned from endocapillary proliferative glomerulonephritis (EnPGN).Methods The clinical data and the results of pathological examination of one case of MPGN transitioned from EnPGN were retrospectively analyzed.Results The child was presented with proteinuria, microscopic hematuria, and persistent low level of complement C3. The type of renal pathology was transitioned from EnPGN to MPGN. Complete remission was achieved in this child with the treatment of oral prednisolone and tacrolimus, but the level of plasma complement C3 remained low.Conclusions The type of renal pathology in children with persistent low level of complement C3 could make a transition, and the early diagnosis, timely and effective treat-ment are important.

  11. Autoimmune disease

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008016 Clinicopathological study of two subtypes of diffuse proliferative lupus nephritis. ZHENG Zhaohui(郑朝晖),et al. Dept Nephrol, 1st Affili Hosp, Zhengzhou Univ , Zhengzhou 450052. Chin J Nephrol 2007;23(11):696-699. Objective To investigate the clinicopathological characteristics and outcome of two subtypes of class Ⅳ lupus nephritis (LN).

  12. Platycodin D from Platycodonis Radix enhances the anti-proliferative effects of doxorubicin on breast cancer MCF-7 and MDA-MB-231 cells

    OpenAIRE

    Tang, Zheng-Hai; Li, Ting; Gao, Hong-wei; Sun, Wen; Chen, Xiu-Ping; Wang, Yi-Tao; Lu, Jin-jian

    2014-01-01

    Background It has been demonstrated that platycodin D (PD) exhibits anti-cancer activities. This study aims to investigate the anti-proliferative effects of the combination of PD and doxorubicin (DOX) on human breast cancer cells (MCF-7 and MDA-MB-231 cells). Methods The anti-proliferative effects of different dosages of PD, DOX, and PD + DOX on MCF-7 and MDA-MB-231 cells were determined by the MTT assay. The 10 μM PD, 5 μM DOX, and 10 μM PD + 5 μM DOX induced-protein expression of apoptosis-...

  13. Bilateral Proliferative Retinopathy Associated With Hoyeraal-Hreidarsson Syndrome, a Severe Form of Dyskeratosis Congenita.

    Science.gov (United States)

    Allingham, Michael J

    2016-04-01

    Dyskeratosis congenita (DC) is the prototypical member of a family of diseases caused by defective telomere maintenance. These "telomeropathies" also include Hoyeraal-Hreidarsson syndrome (HH) and Revesz syndrome, which are severe forms of dyskeratosis congenita, as well as a subset of idiopathic pulmonary fibrosis, aplastic anemia, and Coats' plus syndrome. Retinopathy has only rarely been reported in DC and HH, but is universally present in Coats' plus and Revesz syndromes. The care of these patients is typically a multidisciplinary effort, and this should include monitoring by an ophthalmologist. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:366-368.]. PMID:27065378

  14. Two new oleanane-type triterpenoids from Platycodi Radix and anti-proliferative activity in HSC-T6 cells.

    Science.gov (United States)

    Zhan, Qin; Zhang, Feng; Sun, Lianna; Wu, Zhijun; Chen, Wansheng

    2012-01-01

    Two new oleanane-type triterpenoids, named platycodonoids A and B (1, 2), together with five known saponins, including platycodin D (3), deapioplatycodin D (4), 3-O-β-D-glucopyranosyl polygalacic acid (5), 3-O-β-D-glucopyranosyl platycodigenin (6) and polygalacin D (7), were isolated from the roots of Platycodon grandiflorum. On the basis of spectral data and chemical evidence, the structures of the new compounds were elucidated as 2β,3β,23,24-tetrahydroxy-28-nor-olean-12-en-16-one (1) and 2β,3β,23,24- tetrahydroxy-28-nor-olean-12-en-16-one-3-O-β-D-glucopyranoside (2). Compounds 1-7 were evaluated for their in vitro anti-proliferative activity against the HSC-T6 cell line. PMID:23519261

  15. Two New Oleanane-Type Triterpenoids from Platycodi Radix and Anti-proliferative Activity in HSC-T6 Cells

    Directory of Open Access Journals (Sweden)

    Wansheng Chen

    2012-12-01

    Full Text Available Two new oleanane-type triterpenoids, named platycodonoids A and B (1, 2, together with five known saponins, including platycodin D (3, deapioplatycodin D (4, 3-O-β-D-glucopyranosyl polygalacic acid (5, 3-O-β-D-glucopyranosyl platycodigenin (6 and polygalacin D (7, were isolated from the roots of Platycodon grandiflorum. On the basis of spectral data and chemical evidence, the structures of the new compounds were elucidated as 2β,3β,23,24-tetrahydroxy-28-nor-olean-12-en-16-one (1 and 2β,3β,23,24- tetrahydroxy-28-nor-olean-12-en-16-one-3-O-β-D-glucopyranoside (2. Compounds 1–7 were evaluated for their in vitro anti-proliferative activity against the HSC-T6 cell line.

  16. Hyalinizing trabecular adenoma--a case report with FNAC histologic, MIB-1 proliferative index and immunohistochemical findings.

    Science.gov (United States)

    Karak, A K; Sahoo, M; Bhatnagar, D

    1998-10-01

    Hyalinizing trabecular adenoma is a recently described benign thyroid tumor, almost exclusively occurring in females. The morphological features of this entity overlap with both papillary and medullary carcinoma to varying extent. This, in turn, creates a situation of serious diagnostic pitfall particularly for a false positive diagnosis of papillary carcinoma in fine needle aspiration (FNA) cytology. False consideration of medullary carcinoma is also possible by the unwary especially if staining for Congo red and/or immunostaining for calcitonin is not resorted to. At histologic level, the distinctive architectural pattern is however of great help and thus poses a much lesser danger of misdiagnosis. We relate here our experience in a recently encountered case of hyalinizing trabecular adenoma and describe detailed FNA cytologic and histologic findings along with immunohistochemical profile using a panel of eight monoclonal antibodies. The tumor proliferative potential has also been assessed using MIB-1 (Ki-67) immunostaining. The various pros and cons of diagnostic pitfalls are discussed. PMID:9866913

  17. Ultra violet radiation-induced defects in accessory cell function in the human proliferative response to tetanus

    International Nuclear Information System (INIS)

    Ultraviolet B radiation (290-320 nm) has been shown to interfere with accessory cell function of human peripheral blood mononuclear cells in the generation of a proliferative response to tetanus. By altering the timing of irradiation of adherent cells and using short pulses of antigen, we have identified a minimum of two u.v. sensitive accessory cell functions. The first involves antigen presentation and is not readily reversible with time in culture after irradiation. The second is demonstrated by the ability of low doses of u.v. radiation given after the tetanus toxoid pulse to inhibit an event(s) occuring independent of antigen processing. Both occur within a range of doses which would penetrate to the vasculature of the skin of humans exposed to the sun or to phototherapy. (author)

  18. A RANDOMIZED CLINICAL TRIAL COMPARING EFFICACY OF V ITRECTOMY WITH INTRA VITREAL TRIAMCINOLONE ACETONIDE INJECTIO N AND SIMPLE VITRECTOMY IN PATIENTS WITH VITREOUS HAEMORR HAGE DUE TO PROLIFERATIVE DIABETIC RETINOPATHY

    Directory of Open Access Journals (Sweden)

    Rajeevan

    2013-05-01

    Full Text Available INTRODUCTION: Proliferative diabetic retinopathy affects about 5 -10%of the diabetic population. It is the advanced form of the disease due to ischemic changes and this indicates progression towards more devastating form ie; end stage diabetic eye di sease leading to total blindness. The conventional treatment of this disease has been with laser photo coagulation of the ischemic areas. Serious vision threatening complications of diabetic retinopathy ( Advanced Diabetic Eye Disease [ADED] occur in patients who have not had laser therapy or in whom laser therapy has been unsuccessful. In these groups of patients the treatment is vitrectomy with varying results in regaining and maintaining the regained vision. So Intra Vitreal triamcinolone Ace tonide [IVTA] injection has been tried in many centres, because of its anti inflammatory, anti ang iogenic, cell migration inhibition properties. In t his context to study the efficacy of intravitreal triam cinolone against simple vitrectomy was considered. The comparison of two modes of therapy is best done by a Randomized Controlled Trial. Such studies are not reported from elsewhere in India. Hence thi s study.

  19. 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.

  20. Faster recovery after 25-gauge microincision vitrectomy surgery than after 20-gauge vitrectomy in patients with proliferative diabetic retinopathy

    Directory of Open Access Journals (Sweden)

    Ikeda T

    2012-11-01

    Full Text Available Tatsuhiko Sato, Kazuyuki Emi, Hajime Bando, Toshihide IkedaOsaka Rosai Hospital Clinical Research Center for Occupational Sensory Organ Disability, Sakai, JapanBackground and methods: We compared surgical procedures and outcomes, including duration of recovery period, in eyes with proliferative diabetic retinopathy that underwent 25-gauge microincision vitrectomy surgery with those that underwent 20-gauge vitrectomy. Seventy-two eyes from 53 patients that underwent 20-gauge vitrectomy in 2006 and 87 eyes from 55 patients that underwent 25-gauge vitrectomy in 2010 were studied. The surgical procedures, ie, number of vitreous procedures, operating time, and ratio of type of intraocular tamponade were compared between the two groups. In addition, the outcomes, ie, postoperative complications, anatomical success, postoperative best-corrected visual acuity (BCVA, and duration of hospitalization as an indicator of the postoperative recovery period were also compared.Results: There were no significant differences in surgical procedures or ratio of cases with postoperative complications between cases with 20-gauge and 25-gauge vitrectomy. The final anatomical success rate was 100% in the two groups. BCVA at 6 months after the final vitrectomy was significantly better than the preoperative BCVA for both types of vitrectomy (P < 0.05, and was not significantly different between the two groups. The average duration of hospitalization was 19.5 days after 20-gauge vitrectomy, which was significantly longer than the 11.0 days after 25-gauge vitrectomy (P < 0.001.Conclusion: These results indicate that the anatomical and functional improvements after 25-gauge microincision vitrectomy surgery are not significantly different from those after 20-gauge vitrectomy in eyes with proliferative diabetic retinopathy. However, the significantly shorter recovery period after 25-gauge microincision vitrectomy surgery suggests that it is less traumatic than 20-gauge

  1. Anatomic and functional outcomes of 25-gauge vitrectomy for repair of eyes with rhegmatogenous retinal detachment complicated by proliferative vitreoretinopathy

    Directory of Open Access Journals (Sweden)

    Iwahashi-Shima C

    2013-10-01

    Full Text Available Chiharu Iwahashi-Shima, Tatsuhiko Sato, Hajime Bando, Toshihide Ikeda, Kazuyuki EmiOsaka Rosai Hospital Clinical Research Center for Occupational Sensory Organ Disability, Sakai, JapanBackground: The purpose of this study was to evaluate the outcome of 25-gauge vitrectomy for repair of rhegmatogenous retinal detachment (RRD complicated by proliferative vitreoretinopathy (PVR.Methods: Twenty-seven eyes of 27 patients who had undergone 25-gauge vitrectomy for grade C PVR were investigated retrospectively. The surgical procedures, anatomic success, and best-corrected visual acuity were assessed.Results: The mean number of operations was 1.4 (range 1–4. During the 25-gauge vitrectomy, 20-gauge instruments were needed in eleven eyes (40.7% to remove resilient fibrous preretinal membranes, to extract subretinal proliferations, or to remove or infuse silicone oil. The retina was reattached in 21 eyes (77.8% after the initial vitrectomy and in 25 eyes (92.6% at the final examination. The mean best-corrected visual acuity in logarithm of the minimal angle of resolution units was 1.36 ± 0.81 before vitrectomy and 0.79 ± 0.71 at one month, 0.73 ± 0.72 at 3 months, 0.73 ± 0.75 at 6 months, and 0.75 ± 0.78 at 12 months after vitrectomy. The best-corrected visual acuities were significantly improved compared with the preoperative ones at all postoperative assessments (P<0.001.Conclusion: Twenty-five gauge vitrectomy is a relatively safe and efficacious method of treating RRD with PVR, although combined use of 20-gauge instruments may be needed for certain surgical procedures.Keywords: proliferative vitreoretinopathy, rhegmatogenous retinal detachment, 25-gauge vitrectomy, hybrid vitrectomy, vitrectomy

  2. Autocrine/paracrine proliferative effect of ovarian GH and IGF-I in chicken granulosa cell cultures.

    Science.gov (United States)

    Ahumada-Solórzano, S Marisela; Martínez-Moreno, Carlos G; Carranza, Martha; Ávila-Mendoza, José; Luna-Acosta, José Luis; Harvey, Steve; Luna, Maricela; Arámburo, Carlos

    2016-08-01

    It is known that growth hormone (GH) and its receptor (GHR) are expressed in granulosa cells (GC) and thecal cells during the follicular development in the hen ovary, which suggests GH is involved in autocrine/paracrine actions in the female reproductive system. In this work, we show that the knockdown of local ovarian GH with a specific cGH siRNA in GC cultures significantly decreased both cGH mRNA expression and GH secretion to the media, and also reduced their proliferative rate. Thus, we analyzed the effect of ovarian GH and recombinant chicken GH (rcGH) on the proliferation of pre-hierarchical GCs in primary cultures. Incubation of GCs with either rcGH or conditioned media, containing predominantly a 15-kDa GH isoform, showed that both significantly increased proliferation as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, proliferating cell nuclear antigen (PCNA) quantification and ((3)H)-thymidine incorporation ((3)H-T) assays in a dose response fashion. Both, locally produced GH and rcGH also induced the phosphorylation of Erk1/2 in GC cultures. Furthermore, GH increased IGF-I synthesis and its release into the GC culture incubation media. These results suggest that GH may act through local IGF-I to induce GC proliferation, since IGF-I immunoneutralization completely abolished the GH-induced proliferative effect. These data suggest that GH and IGF-I may play a role as autocrine/paracrine regulators during the follicular development in the hen ovary at the pre-hierarchical stage. PMID:27174747

  3. Oncogenic Role of Skp2 and p27Kip1 in Intraductal Proliferative Lesions of the Breast

    Institute of Scientific and Technical Information of China (English)

    Yan Lv; Yun Niu; Xiu-min Ding; Xu-qi Xiao

    2012-01-01

    Objective To investigate whether the connection of p27Kip1 to S-phase kinase-associated protein 2 (Skp2) plays an oncogenic role in intraductal proliferative lesions of the breast.Methods Here we investigated the mechanism involved in association of Skp2's degradation of p27Kip1 With the breast carcinogenesis by immunohistochemical method through detection of Skp2 and p27Kip1 protein levels in 120 paraffin-embedded tissues of intraductal proliferative lesions including usual ductal hyperplasia (UDH,n=30),atypical ductal hyperplasia (n=30),flat epithelial atypia (FEA,n=30),and ductal carcinoma in situ (DCIS,n=30).Moreover,the expression status of Skp2 and p27Kip1 in 30 cases of the normal breast paraffin-embedded tissues were explored.Results The DCIS group was with the highest Skp2 level and the lowest p27Kip1 level,and the UDH group was with the lowest Skp2 level and the highest p27Kip1 level.Both Skp2 and p27Kip1 levels in the DCIS group were significantly different from those in the UDH group (all P<0.01).The levels of Skp2 and p27Kip1 in the FEA group were significantly different from both the DCIS and UDH groups (all P<0.05).p27Kip1 was negatively correlated with Skp2 in both the UDH group (r=-0.629,P=0.026) and DCIS group (r=-0.893,P=0.000).Conclusion Overexpression of Skp2 might be the mechanism underlying p27Kip1 over degradation.

  4. Tenascin-C in the extracellular matrix promotes the selection of highly proliferative and tubulogenesis-defective endothelial cells

    International Nuclear Information System (INIS)

    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.

  5. Phorbol 12-myristate 13-acetate induces protein kinase ceta-specific proliferative response in astrocytic tumor cells.

    Science.gov (United States)

    Hussaini, I M; Karns, L R; Vinton, G; Carpenter, J E; Redpath, G T; Sando, J J; VandenBerg, S R

    2000-07-21

    Protein kinase C (PKC) activation has been implicated in cellular proliferation in neoplastic astrocytes. The roles for specific PKC isozymes in regulating this glial response, however, are not well understood. The aim of this study was to characterize the expression of PKC isozymes and the role of PKC-eta expression in regulating cellular proliferation in two well characterized astrocytic tumor cell lines (U-1242 MG and U-251 MG) with different properties of growth in cell culture. Both cell lines expressed an array of conventional (alpha, betaI, betaII, and gamma) and novel (theta and epsilon) PKC isozymes that can be activated by phorbol myristate acetate (PMA). Another novel PKC isozyme, PKC-eta, was only expressed by U-251 MG cells. In contrast, PKC-delta was readily detected in U-1242 MG cells but was present only at low levels in U-251 MG cells. PMA (100 nm) treatment for 24 h increased cell proliferation by over 2-fold in the U-251 MG cells, whereas it decreased the mitogenic response in the U-1242 MG cells by over 90%. When PKC-eta was stably transfected into U-1242 MG cells, PMA increased cell proliferation by 2.2-fold, similar to the response of U-251 MG cells. The cell proliferation induced by PMA in both the U-251 MG and U-1242-PKC-eta cells was blocked by the PKC inhibitor bisindolylmaleimide (0.5 micrometer) and the MEK inhibitor, PD 98059 (50 micrometer). Transient transfection of wild type U-251 with PKC-eta antisense oligonucleotide (1 micrometer) also blocked the PMA-induced increase in [(3)H]thymidine incorporation. The data demonstrate that two glioblastoma lines, with functionally distinct proliferative responses to PMA, express different novel PKC isozymes and that the differential expression of PKC-eta plays a determining role in the different proliferative capacity. PMID:10806212

  6. Proliferative kinetics of the haematopoietic stem cells of the mouse after several weeks of reconvalescence of an irradiation attack

    International Nuclear Information System (INIS)

    The 125IDU(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 125IUD 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 125IDU 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)

  7. The nontoxic natural compound Curcumin exerts anti-proliferative, anti-migratory, and anti-invasive properties against malignant gliomas

    International Nuclear Information System (INIS)

    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

  8. Relationship between proliferative activity of cancer cells and clinicopathological factors in patients with esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jun-Xing Huang; Wei Yan; Zheng-Xiang Song; Rong-Yu Qian; Ping Chen; Eeva Salminen; Jorma Toppari

    2005-01-01

    AIM: To assess whether the molecular markers of malignant tumors could improve the understanding of tumor characteristics, and to observe the characteristics of expression of cell cycle markers Ki-67 and cydin A in esophageal carcinoma and to analyze the relationship between proliferative activity of cancer cells and clinicopathological factors.METHODS: Seventy of surgically resected esophageal squamous cell carcinoma (SCC) were examined by immunohistochemistry utilizing commercially available antibodies. Nuclear staining was regarded as a positive result. At least 50 fields in each tumor and non-tumor section were evaluated at a medium power (x200) to determine the proportion of tumor cells and the staining intensity of nuclei in the entire sections.RESULTS: Ki-67 and cyclin A were only expressed in base cells of normal esophageal mucosa. The positive immunostaining of nuclei of SCC was significantly higher than that in normal esophageal mucosa (t= 13.32 and t= 7.52,respectively, P<0.01). The distribution of positively stained was more diffuse and stronger in poorly differentiated SCC. Both Ki-67 and cyclin A expressions were related to histological grades of tumors (t = 3.5675 and t = 3.916; t= 2.13, respectively, P<0.05) but not to the sex and age of the patients, tumor size, lymphatic invasion, location, or stage grouping.CONCLUSION: The proliferative activity of cancer cells may be understood by immunohistochemistry of Ki-67 and cyclin A in Chinese patients with esophageal SCC. These cell cycle markers may serve as an indicator of cancer cell proliferation rate. The overexpression of cell cycle markers Ki-67 and cyclin A suggests the poor SCC differentiation in patients with esophageal carcinoma.

  9. Infectious prions accumulate to high levels in non proliferative C2C12 myotubes.

    Directory of Open Access Journals (Sweden)

    Allen Herbst

    Full Text Available Prion diseases are driven by the strain-specific, template-dependent transconformation of the normal cellular prion protein (PrP(C into a disease specific isoform PrP(Sc. Cell culture models of prion infection generally use replicating cells resulting in lower levels of prion accumulation compared to animals. Using non-replicating cells allows the accumulation of higher levels of PrP(Sc and, thus, greater amounts of infectivity. Here, we infect non-proliferating muscle fiber myotube cultures prepared from differentiated myoblasts. We demonstrate that prion-infected myotubes generate substantial amounts of PrP(Sc and that the level of infectivity produced in these post-mitotic cells, 10(5.5 L.D.50/mg of total protein, approaches that observed in vivo. Exposure of the myotubes to different mouse-adapted agents demonstrates strain-specific replication of infectious agents. Mouse-derived myotubes could not be infected with hamster prions suggesting that the species barrier effect is intact. We suggest that non-proliferating myotubes will be a valuable model system for generating infectious prions and for screening compounds for anti-prion activity.

  10. TrkB Receptor Signalling: Implications in Neurodegenerative, Psychiatric and Proliferative Disorders

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    Stuart L. Graham

    2013-05-01

    Full Text Available The Trk family of receptors play a wide variety of roles in physiological and disease processes in both neuronal and non-neuronal tissues. Amongst these the TrkB receptor in particular has attracted major attention due to its critical role in signalling for brain derived neurotrophic factor (BDNF, neurotrophin-3 (NT3 and neurotrophin-4 (NT4. TrkB signalling is indispensable for the survival, development and synaptic plasticity of several subtypes of neurons in the nervous system. Substantial evidence has emerged over the last decade about the involvement of aberrant TrkB signalling and its compromise in various neuropsychiatric and degenerative conditions. Unusual changes in TrkB signalling pathway have also been observed and implicated in a range of cancers. Variations in TrkB pathway have been observed in obesity and hyperphagia related disorders as well. Both BDNF and TrkB have been shown to play critical roles in the survival of retinal ganglion cells in the retina. The ability to specifically modulate TrkB signalling can be critical in various pathological scenarios associated with this pathway. In this review, we discuss the mechanisms underlying TrkB signalling, disease implications and explore plausible ameliorative or preventive approaches.

  11. 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…

  12. Tumor suppressor ASXL1 is essential for the activation of INK4B expression in response to oncogene activity and anti-proliferative signals

    DEFF Research Database (Denmark)

    Wu, Xudong; Bekker-Jensen, Ida Holst; Christensen, Jesper;

    2015-01-01

    deubiquitylation plays a role in its activation. Interestingly, we found that ASXL1 is specifically required for the increased expression of p15(INK4B) in response to both oncogenic signaling and extrinsic anti-proliferative signals. Since we found that ASXL1 and BAP1 both are enriched at the INK4B locus, our...

  13. Proliferative activity (MIB-1 index) is an independent prognostic parameter in patients with high-grade soft tissue sarcomas of subtypes other than malignant fibrous histiocytomas

    DEFF Research Database (Denmark)

    Jensen, V; Sørensen, Flemming Brandt; Bentzen, S M;

    1998-01-01

    AIMS: To evaluate the prognostic value of tumour proliferative activity, p53 accumulation and bcl-2 expression in a retrospective series of 216 patients with soft tissue sarcomas (STS). METHODS AND RESULTS: The immunohistochemical analyses were performed on formalin-fixed, paraffin-embedded tissue...

  14. Minimal-Change Disease Secondary to Borrelia burgdorferi Infection

    OpenAIRE

    Ewa Kwiatkowska; Edyta Gołembiewska; Kazimierz Ciechanowski; Karolina Kędzierska

    2012-01-01

    Lyme borreliosis is a chronic illness caused by tick-transmitted spirochete Borrelia burgdorferi. Borreliosis can be extremely threatening if it is not diagnosed and treated in early stages. Kidneys are not typically involved in the disease. However, in infected dogs, Lyme nephritis is present in 5–10% of cases. It is associated with rapidly progressing renal failure. Histopathological examination shows mesangial proliferative glomerulonephritis with diffuse tubular necrosis, (Dambach et al. ...

  15. Brachytherapy in coronary artery disease

    Energy Technology Data Exchange (ETDEWEB)

    Song, Ho Chun [Chonnam National University Medicine School, Gwangju (Korea, Republic of)

    2006-04-15

    Coronary artery disease is a leading cause of morbidity and mortality across the world. Percutaneous coronary intervention has become the major technique of revascularization. However, restenosis remains a major limitation of this procedure. Recently the need for repeat intervention due to restenosis, the most vexing long-term failure of percutaneous coronary intervention, has been significantly reduced owing to the introduction to two major advances, intracoronary brachytherapy and the drug-eluting stents, intracoronary brachytherapy has been employed in recent years to prevent restenosis lesions with effective results, principally in in-stent restenosis. Restenosis is generally considered as an excessive form of normal wound healing divided up in processes: elastic recoil, neointimal hyperplasia, and negative vascular remodeling. Restenosis has previously been regarded as a proliferative process in which neointimal thickening, mediated by a cascade of inflammatory mediators and other factors, is the key factor. Ionizing radiation has been shown to decrease the proliferative response to injury in animal models of restenosis. Subsequently, several randomized, double-blind trials have demonstrated that intracoronary brachytherapy can reduce the rates to both angiographic restenosis and clinical event rates in patients undergoing percutaneous coronary intervention for in-stent restenosis. Some problems, such as late thrombosis and edge restenosis, have been identified as limiting factors of this technique. Brachytherapy is a promising method of preventing and treating coronary artery restenosis.

  16. Allopregnanolone-induced rise in intracellular calcium in embryonic hippocampal neurons parallels their proliferative potential

    Directory of Open Access Journals (Sweden)

    Brinton Roberta

    2008-12-01

    Full Text Available Abstract Background Factors that regulate intracellular calcium concentration are known to play a critical role in brain function and neural development, including neural plasticity and neurogenesis. We previously demonstrated that the neurosteroid allopregnanolone (APα; 5α-pregnan-3α-ol-20-one promotes neural progenitor proliferation in vitro in cultures of rodent hippocampal and human cortical neural progenitors, and in vivo in triple transgenic Alzheimer's disease mice dentate gyrus. We also found that APα-induced proliferation of neural progenitors is abolished by a calcium channel blocker, nifedipine, indicating a calcium dependent mechanism for the proliferation. Methods In the present study, we investigated the effect of APα on the regulation of intracellular calcium concentration in E18 rat hippocampal neurons using ratiometric Fura2-AM imaging. Results Results indicate that APα rapidly increased intracellular calcium concentration in a dose-dependent and developmentally regulated manner, with an EC50 of 110 ± 15 nM and a maximal response occurring at three days in vitro. The stereoisomers 3β-hydroxy-5α-hydroxy-pregnan-20-one, and 3β-hydroxy-5β-hydroxy-pregnan-20-one, as well as progesterone, were without significant effect. APα-induced intracellular calcium concentration increase was not observed in calcium depleted medium and was blocked in the presence of the broad spectrum calcium channel blocker La3+, or the L-type calcium channel blocker nifedipine. Furthermore, the GABAA receptor blockers bicuculline and picrotoxin abolished APα-induced intracellular calcium concentration rise. Conclusion Collectively, these data indicate that APα promotes a rapid, dose-dependent, stereo-specific, and developmentally regulated increase of intracellular calcium concentration in rat embryonic hippocampal neurons via a mechanism that requires both the GABAA receptor and L-type calcium channel. These data suggest that AP

  17. Proliferative effect of Hachimijiogan, a Japanese herbal medicine, in C2C12 skeletal muscle cells

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    Takeda T

    2015-02-01

    Full Text Available Takashi Takeda,1,2 Kenji Tsuiji,2 Bin Li,2 Mari Tadakawa,2 Nobuo Yaegashi2 1Division of Women’s Health, Research Institute of Traditional Asian Medicine, Kinki University School of Medicine, Osaka, Japan; 2Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Sendai, Japan Background: Hachimijiogan (HJG, Ba-Wei-Di-Huang-Wan in Chinese, is one of the most popular herbal medicines in Japanese Kampo. HJG is often prescribed for the prevention and treatment of age-related diseases. Muscle atrophy plays an important role in aging-related disabilities such as sarcopenia. The purpose of this study was to investigate the possible beneficial effect of HJG on skeletal muscle.Methods: Cells of murine skeletal muscle myoblast cell line C2C12 were used as an in vitro model of muscle cell proliferation and differentiation. The effect of HJG on C2C12 cell proliferation and differentiation was assessed. We counted the number of myotubes morphologically to assess the degree of differentiation.Results: HJG treatment (200 µg/mL for 3 days significantly increased C2C12 cell number by 1.23-fold compared with that of the control. HJG promoted the proliferation of C2C12 cells through activation of the ERK1/2 signaling pathway without affecting the Akt signaling pathway. HJG did not affect the differentiation of C2C12 cells. Conclusion: HJG had beneficial effects on skeletal muscle myoblast proliferation. These findings may provide a useful intervention for the prevention and treatment of sarcopenia. Keywords: ERK1/2 signaling pathway, herbal medicine, myoblast, proliferation, sarcopenia

  18. The anti-proliferative effect of L-carnosine correlates with a decreased expression of hypoxia inducible factor 1 alpha in human colon cancer cells.

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    Barbara Iovine

    Full Text Available In recent years considerable attention has been given to the use of natural substances as anticancer drugs. The natural antioxidant dipeptide L-carnosine belongs to this class of molecules because it has been proved to have a significant anticancer activity both in vitro and in vivo. Previous studies have shown that L-carnosine inhibits the proliferation of human colorectal carcinoma cells by affecting the ATP and Reactive Oxygen Species (ROS production. In the present study we identified the Hypoxia-Inducible Factor 1α (HIF-1α as a possible target of L-carnosine in HCT-116 cell line. HIF-1α protein is over-expressed in multiple types of human cancer and is the major cause of resistance to drugs and radiation in solid tumours. Of particular interest are experimental data supporting the concept that generation of ROS provides a redox signal for HIF-1α induction, and it is known that some antioxidants are able to suppress tumorigenesis by inhibiting HIF-1α. In the current study we found that L-carnosine reduces the HIF-1α protein level affecting its stability and decreases the HIF-1 transcriptional activity. In addition, we demonstrated that L-carnosine is involved in ubiquitin-proteasome system promoting HIF-1α degradation. Finally, we compared the antioxidant activity of L-carnosine with that of two synthetic anti-oxidant bis-diaminotriazoles (namely 1 and 2, respectively. Despite these three compounds have the same ability in reducing intracellular ROS, 1 and 2 are more potent scavengers and have no effect on HIF-1α expression and cancer cell proliferation. These findings suggest that an analysis of L-carnosine antioxidant pathway will clarify the mechanism underlying the anti-proliferative effects of this dipeptide on colon cancer cells. However, although the molecular mechanism by which L-carnosine down regulates or inhibits the HIF-1α activity has not been yet elucidated, this ability may be promising in treating hypoxia

  19. The anti-proliferative effect of L-carnosine correlates with a decreased expression of hypoxia inducible factor 1 alpha in human colon cancer cells.

    Science.gov (United States)

    Iovine, Barbara; Oliviero, Giorgia; Garofalo, Mariangela; Orefice, Maria; Nocella, Francesca; Borbone, Nicola; Piccialli, Vincenzo; Centore, Roberto; Mazzone, Massimiliano; Piccialli, Gennaro; Bevilacqua, Maria Assunta

    2014-01-01

    In recent years considerable attention has been given to the use of natural substances as anticancer drugs. The natural antioxidant dipeptide L-carnosine belongs to this class of molecules because it has been proved to have a significant anticancer activity both in vitro and in vivo. Previous studies have shown that L-carnosine inhibits the proliferation of human colorectal carcinoma cells by affecting the ATP and Reactive Oxygen Species (ROS) production. In the present study we identified the Hypoxia-Inducible Factor 1α (HIF-1α) as a possible target of L-carnosine in HCT-116 cell line. HIF-1α protein is over-expressed in multiple types of human cancer and is the major cause of resistance to drugs and radiation in solid tumours. Of particular interest are experimental data supporting the concept that generation of ROS provides a redox signal for HIF-1α induction, and it is known that some antioxidants are able to suppress tumorigenesis by inhibiting HIF-1α. In the current study we found that L-carnosine reduces the HIF-1α protein level affecting its stability and decreases the HIF-1 transcriptional activity. In addition, we demonstrated that L-carnosine is involved in ubiquitin-proteasome system promoting HIF-1α degradation. Finally, we compared the antioxidant activity of L-carnosine with that of two synthetic anti-oxidant bis-diaminotriazoles (namely 1 and 2, respectively). Despite these three compounds have the same ability in reducing intracellular ROS, 1 and 2 are more potent scavengers and have no effect on HIF-1α expression and cancer cell proliferation. These findings suggest that an analysis of L-carnosine antioxidant pathway will clarify the mechanism underlying the anti-proliferative effects of this dipeptide on colon cancer cells. However, although the molecular mechanism by which L-carnosine down regulates or inhibits the HIF-1α activity has not been yet elucidated, this ability may be promising in treating hypoxia-related diseases. PMID

  20. Characterization of the early proliferative response of the rodent bladder to subtotal cystectomy: a unique model of mammalian organ regeneration.

    Directory of Open Access Journals (Sweden)

    Charles C Peyton

    Full Text Available Subtotal cystectomy (STC; surgical removal of ∼75% of the rat urinary bladder elicits a robust proliferative response resulting in complete structural and functional bladder regeneration within 8-weeks. The goal of these studies was to characterize the early cellular response that mediates this regenerative phenomenon, which is unique among mammalian organ systems. STC was performed on eighteen 12-week-old female Fischer F344 rats. At 1, 3, 5 and 7-days post-STC, the bladder was harvested 2-hours after intraperitoneal injection of bromodeoxyuridine (BrdU. Fluorescent BrdU labeling was quantified in cells within the urothelium, lamina propria (LP, muscularis propria (MP and serosa. Cell location was confirmed with fluorescently co-labeled cytokeratin, vimentin or smooth muscle actin (SMA, to identify urothelial, interstitial and smooth muscle cells, respectively. Expression of sonic hedgehog (Shh, Gli-1 and bone morphogenic factor-4 (BMP-4 were evaluated with immunochemistry. Three non-operated rats injected with BrdU served as controls. Less than 1% of cells in the bladder wall were labeled with BrdU in control bladders, but this percentage significantly increased by 5-8-fold at all time points post-STC. The spatiotemporal characteristics of the proliferative response were defined by a significantly higher percentage of BrdU-labeled cells within the urothelium at 1-day than in the MP and LP. A time-dependent shift at 3 and 5-days post-STC revealed significantly fewer BrdU-labeled cells in the MP than LP or urothelium. By 7-days the percentage of BrdU-labeled cells was similar among urothelium, LP and MP. STC also caused an increase in immunostaining for Shh, Gli-1 and BMP-4. In summary, the early stages of functional bladder regeneration are characterized by time-dependent changes in the location of the proliferating cell population, and expression of several evolutionarily conserved developmental signaling proteins. This report extends

  1. Prolonged effect of fluid flow stress on the proliferative activity of mesothelial cells after abrupt discontinuation of fluid streaming

    Energy Technology Data Exchange (ETDEWEB)

    Aoki, Shigehisa, E-mail: aokis@cc.saga-u.ac.jp [Department of Pathology and Microbiology, Faculty of Medicine, Saga University, Saga (Japan); Ikeda, Satoshi [Department of Pathology and Microbiology, Faculty of Medicine, Saga University, Saga (Japan); Takezawa, Toshiaki [Transgenic Animal Research Center, National Institute of Agrobiological Sciences, Ibaraki (Japan); Kishi, Tomoya [Department of Internal Medicine, Saga University, Saga (Japan); Makino, Junichi [Makino Clinic, Saga (Japan); Uchihashi, Kazuyoshi; Matsunobu, Aki [Department of Pathology and Microbiology, Faculty of Medicine, Saga University, Saga (Japan); Noguchi, Mitsuru [Department of Urology, Faculty of Medicine, Saga University, Saga (Japan); Sugihara, Hajime [Department of Physical Therapy, International University of Health and Welfare, Fukuoka (Japan); Toda, Shuji [Department of Pathology and Microbiology, Faculty of Medicine, Saga University, Saga (Japan)

    2011-12-16

    Highlights: Black-Right-Pointing-Pointer Late-onset peritoneal fibrosis leading to EPS remains to be elucidated. Black-Right-Pointing-Pointer Fluid streaming is a potent factor for peritoneal fibrosis in PD. Black-Right-Pointing-Pointer We focused on the prolonged effect of fluid streaming on mesothelial cell kinetics. Black-Right-Pointing-Pointer A history of fluid streaming exposure promoted mesothelial proliferative activity. Black-Right-Pointing-Pointer We have thus identified a potent new factor for late-onset peritoneal fibrosis. -- Abstract: Encapsulating peritoneal sclerosis (EPS) often develops after transfer to hemodialysis and transplantation. Both termination of peritoneal dialysis (PD) and transplantation-related factors are risks implicated in post-PD development of EPS, but the precise mechanism of this late-onset peritoneal fibrosis remains to be elucidated. We previously demonstrated that fluid flow stress induced mesothelial proliferation and epithelial-mesenchymal transition via mitogen-activated protein kinase (MAPK) signaling. Therefore, we speculated that the prolonged bioactive effect of fluid flow stress may affect mesothelial cell kinetics after cessation of fluid streaming. To investigate how long mesothelial cells stay under the bioactive effect brought on by fluid flow stress after removal of the stress, we initially cultured mesothelial cells under fluid flow stress and then cultured the cells under static conditions. Mesothelial cells exposed to fluid flow stress for a certain time showed significantly high proliferative activity compared with static conditions after stoppage of fluid streaming. The expression levels of protein phosphatase 2A, which dephosphorylates MAPK, in mesothelial cells changed with time and showed a biphasic pattern that was dependent on the duration of exposure to fluid flow stress. There were no differences in the fluid flow stress-related bioactive effects on mesothelial cells once a certain time had passed

  2. A comparative immunohistochemical study of aplastic thymuses for lymphocytic, epithelial, proliferative and apoptotic indices

    Directory of Open Access Journals (Sweden)

    Mahjoub F.

    2008-03-01

    Full Text Available Background: Immune deficiency is one of the major causes of morbidity and mortality in the modern world. Primary immunodeficiency comprises a wide range of disorders that mainly manifest in early childhood as devastating infections with opportunistic organisms. Thymic aplasia is found on autopsy of some patients afflicted with immune deficiency disorders, such as DiGeorge syndrome and severe combined immunodeficiency (SCID. After a thorough search of the literature, we found little information on the cellular characteristics of these thymuses. Our study aims to elucidate role of apoptosis in the pathogenesis of thymic aplasia and compare various lymphocytic and epithelial markers in normal and aplastic thymuses. Methods: We selected 12 subjects who died of severe infections with aplastic thymus found on autopsy, and 11 control subjects who died of unrelated causes, such as congenital heart disease. The presence of several markers, including Bcl2, P53, lymphocytic markers, and CD68, was examined using immunohistochemical methods on paraffin-embedded thymus sections. Positively-stained cells were counted per 1000 cells and the results stated as percentage of positive cells.                        Results: The mean age of the control group was between 7 days to 18 months (mean: 4.5 months. Parental consanguinity was present in 45.5% and 9.1% of the control and case groups, respectively; however, this was not statistically significant. We found significantly lower expression of Bcl2 in the case group (p value: 0.038. Furthermore, expression of CD68 was significantly higher in the case group. Epithelial markers were significantly higher in case subjects, although CD8 expression was higher in the control group. The presence of other markers was not significantly different between the two groups.Conclusions: Increase in apoptosis has a role in aplastic thymuses and prevention of apoptosis may halt this process. Also high CD68

  3. Pathogenesis of glomerulosclerosis in light chain deposition disease. Role for transforming growth factor-beta.

    OpenAIRE

    Zhu, L.; Herrera, G. A.; Murphy-Ullrich, J. E.; Huang, Z.Q.; Sanders, P W

    1995-01-01

    The glomerulopathy of monoclonal immunoglobulin light chain deposition disease is a progressive disorder characterized by accumulation of monoclonal light chains and matrix proteins in the mesangium. To define the role of light chains in this process, cultured rat mesangial cells were exposed to different light chains and human albumin. Two light chains were purified from the urine of patients who had biopsy-proven light chain deposition disease. These proteins inhibited mesangial cell prolif...

  4. Migration Status and Prevalence of Chronic Diseases in Kerala State, India

    OpenAIRE

    Safraj Shahul Hameed; Vellapallil Raman Kutty; Krishnapillai Vijayakumar; Ajayan Kamalasanan

    2013-01-01

    Aim. To study the relationship between a personal history of migration and prevalence of chronic diseases and risk factors in a rural population. Method. Cross sectional survey data from PROLIFE, a cohort study involving the long time follow-up of the residents of an administrative unit in Kerala, India, was used. Pre-tested questionnaire was administered to 78,173 adult residents. Information on physician diagnosed diabetes, hypertension, and cardiac diseases and lifestyle attributes like ph...

  5. Towards integrated control of East Cost fever, a devastating disease of cattle

    OpenAIRE

    Olds, Cassandra Leah

    2013-01-01

    Infection of cattle with the tick-borne apicomplexan parasite Theileria parva results in the fatal lympho-proliferative disease known as East Coast fever (ECF). ECF is considered to be one of the most devastating diseases of livestock in sub-Saharan Africa affecting all sectors of livestock production. The three-host brown ear tick, Rhipicephalus appendiculatus is the primary vector of T. parva with all tick life stages adapted to feeding on cattle. Currently, there is no effective vaccine ag...

  6. Filament formation associated with spirochetal infection: a comparative approach to Morgellons disease

    OpenAIRE

    Middelveen MJ; Stricker RB

    2011-01-01

    Marianne J Middelveen, Raphael B StrickerInternational Lyme and Associated Diseases Society, Bethesda, MD, USAAbstract: Bovine digital dermatitis is an emerging infectious disease that causes lameness, decreased milk production, and weight loss in livestock. Proliferative stages of bovine digital dermatitis demonstrate keratin filament formation in skin above the hooves in affected animals. The multifactorial etiology of digital dermatitis is not well understood, but spirochetes and other coi...

  7. Biological Characterization of Cynara cardunculus L. Methanolic Extracts: Antioxidant, Anti-proliferative, Anti-migratory and Anti-angiogenic Activities

    Directory of Open Access Journals (Sweden)

    Maria Duarte

    2012-12-01

    Full Text Available Cynara cardunculus (Cc is a multipurpose species; beyond its use in southwestern European cuisine, it is also used for the production of solid biofuel, seed oil, biodiesel, paper pulp and cheese, as well as animal feed. In addition, Cc has a long tradition of use in folk medicine as a diuretic and liver protector. The value of this species as a source of bioactive compounds is known; however, pharmacological use would further increase its cultivation. The main goal of the current work was to evaluate the potential of Cc as source of anti-carcinogenic phytochemicals. Different methanolic extracts obtained from wild and cultivated plants were tested for antioxidant activity and effect on breast tumor cell viability. The most effective extract, both as antioxidant and inhibition of tumor cell viability, was tested for effects on angiogenesis and tumor cell migration capacity. All the extracts tested had high antioxidant activity; however, only green leaves and dry head extracts exhibit anti-proliferative activity. Green cultivated leaves (GCL were the most effective extract both as antioxidant and inhibiting the proliferation of tumor cells; it is equally active inhibiting tumor cell migration and in vivo angiogenesis. GCL extract is an effective inhibitor of several key points in tumor development and thus a promising source of anti-carcinogenic phytochemicals.

  8. Anti-proliferative effect of leaf extracts of Eucalyptus citriodora against human cancer cells in vitro and in vivo.

    Science.gov (United States)

    Bhagat, Madhulika; Sharma, Vikas; Saxena, Ajit Kumar

    2012-12-01

    Six different extracts from Eucalyptus citriodora leaves were investigated for their anticancer effect. Extracts were prepared using a range of polar and non-polar solvents to leach out maximum active components. Phytochemical analysis of the extracts revealed the presence of anthraquinones, cardiac glycosides, flavonoids, saponins and tannins. Cytotoxic activity of different extracts was tested in vitro against seven human cancer cell lines from seven different tissues, such as SW-620 (colon), HOP-62 (lung), PC-3 (prostate), OVCAR-5 (ovary), HeLa (cervix), IMR-32 (neuroblastoma) and HEP-2 (liver). The ethyl acetate, chloroform and 50% methanolic extract displayed highest anti-proliferative effect in a dose-dependent manner. In vivo anti-tumor activity was evaluated against murine tumor (solid) model of Ehrlich ascites carcinoma and Sarcoma 180. The results showed that ethyl acetate and aqueous extracts suppressed the growth of Ehrlich ascites carcinoma (29.79% and 18.48%, respectively), but showed little growth inhibition in case of Sarcoma 180 (13. 86% and 8.57%, respectively). The activity might be due to the flavonoids, tannins and saponins that are present in all the extracts of the plant. Further investigation is required for the isolation of active principle(s) from the ethyl acetate extract, which has shown significant in vitro and in vivo anticancer potential. PMID:23350280

  9. Facile modification of gelatin-based microcarriers with multiporous surface and proliferative growth factors delivery to enhance cell growth

    International Nuclear Information System (INIS)

    The design of microcarriers plays an important role in the success of cell expansion. The present article provides a facile approach to modify the gelatin-based particles and investigates the feasibility of their acting as microcarriers for cell attachment and growth. Gelatin particles (150-320 μm) were modified by cryogenic treatment and lyophilization to develop the surface with the features of multiporous morphology and were incorporated with proliferative growth factors (bFGF) by adsorption during the post-preparation, which enables them to serve as microcarriers for cells amplification, together with the advantages of larger cell-surface contact area and capability of promoting cell propagation. The microstructure and release assay of the modified microcarriers demonstrated that the pores on surface were uniform and bFGF was released in a controlled manner. Through in vitro fibroblast culture, these features resulted in a prominent increase in the cell attachment rate and cell growth rate relative to the conditions without modification. Although the scanning electron microscopy and optical microscopy analysis results indicated that cells attached, spread, and proliferated on all the microcarriers, cell growth clearly showed a significant correlation with the multiporous structure of microcarriers, in particular on bFGF combined ones. These results validate our previous assumption that the facile modification could improve cell growth on the gelatin-based microcarriers obviously and the novel microcarriers may be a promising candidate in tissue engineering

  10. Progression to macula-off tractional retinal detachment after a contralateral intraoperative intravitreal bevacizumab injection for proliferative diabetic retinopathy

    Directory of Open Access Journals (Sweden)

    Zlotcavitch L

    2015-01-01

    Full Text Available Leonid Zlotcavitch,1 Harry W Flynn Jr,2 Robert L Avery,3 Aleksandra Rachitskaya2 1University of Miami, Miller School of Medicine, 2Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami, Miller School of Medicine, Miami, FL, USA; 3California Retina Consultants, Santa Barbara, CA, USA Abstract: We report a patient with progression to a macula-off tractional retinal detachment in a fellow eye after a contralateral intraoperative intravitreal bevacizumab injection. A 32-year-old diabetic man noted decreased vision in his left eye 1 week following 25 gauge pars plana vitrectomy, gas tamponade, and intraoperative injection of bevacizumab in his right eye. Left eye visual acuity decreased from 20/80 to 20/200, and macula-off tractional retinal detachment was seen on clinical exam and imaging. Progression of tractional retinal detachment associated with proliferative diabetic retinopathy in a fellow eye after a contralateral intraoperative intravitreal bevacizumab injection may occur. Keywords: anti-VEGF therapy, fellow eye, tractional retinal detachment, diabetes mellitus

  11. Facile modification of gelatin-based microcarriers with multiporous surface and proliferative growth factors delivery to enhance cell growth

    Energy Technology Data Exchange (ETDEWEB)

    Huang Sha [Department of Oral Histology and Pathology, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China); Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi' an 710032 (China); Wang Yijuan [Key Laboratory for Macromolecular Science of Shaanxi Province, Shaanxi Normal University, Xi' an 710062 (China); Deng, Tianzheng [Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi' an 710032 (China); Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China); Jin Fang [Department of Orthodontics, School of Stomatology, Fourth Military Medical University, Xi' an, 710032 (China); Liu Shouxin [Key Laboratory for Macromolecular Science of Shaanxi Province, Shaanxi Normal University, Xi' an 710062 (China); Zhang Yongjie [Department of Oral Histology and Pathology, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China); Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi' an 710032 (China); Feng Feng [Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi' an 710032 (China); Department of Dermatology, Tangdu Hospital, Fourth Military Medical University, Xi' an 710038 (China); Jin Yan [Department of Oral Histology and Pathology, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China); Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi' an 710032 (China)], E-mail: yanjin@fmmu.edu.cn

    2008-07-28

    The design of microcarriers plays an important role in the success of cell expansion. The present article provides a facile approach to modify the gelatin-based particles and investigates the feasibility of their acting as microcarriers for cell attachment and growth. Gelatin particles (150-320 {mu}m) were modified by cryogenic treatment and lyophilization to develop the surface with the features of multiporous morphology and were incorporated with proliferative growth factors (bFGF) by adsorption during the post-preparation, which enables them to serve as microcarriers for cells amplification, together with the advantages of larger cell-surface contact area and capability of promoting cell propagation. The microstructure and release assay of the modified microcarriers demonstrated that the pores on surface were uniform and bFGF was released in a controlled manner. Through in vitro fibroblast culture, these features resulted in a prominent increase in the cell attachment rate and cell growth rate relative to the conditions without modification. Although the scanning electron microscopy and optical microscopy analysis results indicated that cells attached, spread, and proliferated on all the microcarriers, cell growth clearly showed a significant correlation with the multiporous structure of microcarriers, in particular on bFGF combined ones. These results validate our previous assumption that the facile modification could improve cell growth on the gelatin-based microcarriers obviously and the novel microcarriers may be a promising candidate in tissue engineering.

  12. Expression of p75NGFR, a Proliferative and Basal Cell Marker, in the Buccal Mucosa Epithelium during Re-epithelialization

    International Nuclear Information System (INIS)

    We investigated the expression of p75NGFR, a proliferative and basal cell marker, in the mouse buccal mucosa epithelium during wound healing in order to elucidate the role of epithelial stem cells. Epithelial defects were generated in the epithelium of the buccal mucosa of 6-week-old mice using CO2 laser irradiation. BrdU was immediately administered to mice following laser irradiation. They were then sacrificed after 1, 3, 7, and 14 days. Paraffin sections were prepared and the irradiated areas were analyzed using immunohistochemistry with anti-p75NGFR, BrdU, PCNA, and CK14 antibodies. During re-epithelialization, PCNA (–)/p75NGFR (+) cells extended to the wound, which then closed, whereas PCNA (+)/p75NGFR (+) cells were not observed at the edge of the wound. In addition, p75NGFR (–)/CK14 (+), which reflected the presence of post-mitotic differentiating cells, was observed in the supra-basal layers of the extended epithelium. BrdU (+)/p75NGFR (+), which reflected the presence of epithelial stem cells, was detected sparsely in buccal basal epithelial cells after healing, and disappeared after 7 days. These results suggest that p75NGFR (+) keratinocytes are localized in the basal layer, which contains oral epithelial stem cells, and retain the ability to proliferate in order to regenerate the buccal mucosal epithelium

  13. Nonproliferative and Proliferative Lesions of the Gastrointestinal Tract, Pancreas and Salivary Glands of the Rat and Mouse.

    Science.gov (United States)

    Nolte, Thomas; Brander-Weber, Patricia; Dangler, Charles; Deschl, Ulrich; Elwell, Michael R; Greaves, Peter; Hailey, Richard; Leach, Michael W; Pandiri, Arun R; Rogers, Arlin; Shackelford, Cynthia C; Spencer, Andrew; Tanaka, Takuji; Ward, Jerrold M

    2016-01-01

    The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) project is a joint initiative of the Societies of Toxicologic Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP), and North America (STP) to develop an internationally accepted nomenclature and diagnostic criteria for nonproliferative and proliferative lesions in laboratory animals. The purpose of this publication is to provide a standardized nomenclature and diagnostic criteria for classifying lesions in the digestive system including the salivary glands and the exocrine pancreas of laboratory rats and mice. Most lesions are illustrated by color photomicrographs. The standardized nomenclature, the diagnostic criteria, and the photomicrographs are also available electronically on the Internet (http://www.goreni.org/). Sources of material included histopathology databases from government, academia, and industrial laboratories throughout the world. Content includes spontaneous and age related lesions as well as lesions induced by exposure to test items. Relevant infectious and parasitic lesions are included as well. A widely accepted and utilized international harmonization of nomenclature and diagnostic criteria for the digestive system will decrease misunderstandings among regulatory and scientific research organizations in different countries and provide a common language to increase and enrich international exchanges of information among toxicologists and pathologists. PMID:26973378

  14. Conformational study reveals amino acid residues essential for hemagglutinating and anti-proliferative activities of Clematis montana lectin.

    Science.gov (United States)

    Lu, Bangmin; Zhang, Bin; Qi, Wei; Zhu, Yanan; Zhao, Yan; Zhou, Nan; Sun, Rong; Bao, Jinku; Wu, Chuanfang

    2014-11-01

    Clematis montana lectin (CML), a novel mannose-binding lectin purified from C. montana Buch.-Ham stem (Ranunculaceae), has been proved to have hemagglutinating activity in rabbit erythrocytes and apoptosis-inducing activity in tumor cells. However, the biochemical properties of CML have not revealed and its structural information still needs to be elucidated. In this study, it was found that CML possessed quite good thermostability and alkaline resistance, and its hemagglutinating activity was bivalent metal cation dependent. In addition, hemagglutination test and fluorescence spectroscopy proved that GuHCl, urea, and sodium dodecyl sulfate could change the conformation of CML and further caused the loss of hemagglutination activity. Moreover, the changes of fluorescence spectrum indicated that the tryptophan (Trp) microenvironment conversion might be related to the conformation and bioactivities of CML. In addition, it was also found that Trp residues, arginine (Arg) residues, and sulfhydryl were important for the hemagglutinating activity of CML, but only Trp was proved to be crucial for the CML conformation. Furthermore, the Trp, Arg, and sulfhydryl-modified CML exhibited 97.17%, 76.99%, and 49.64% loss of its anti-proliferative activity, respectively, which was consistent with the alterations of its hemagglutinating activity. Given these findings, Trp residues on the surface of CML are essential for the active center to form substrate-accessible conformation and suitable environment for carbohydrate binding. PMID:25239139

  15. A Histopathological Study of Multi-hormone Producing Proliferative Lesions in Estrogen-induced Rat Pituitary Prolactinoma

    International Nuclear Information System (INIS)

    Rats with estrogen-induced prolactin-producing pituitary adenoma (E2-PRLoma) have been employed as an animal model of human PRL-producing pituitary adenoma in a large number of studies. Presently, we found that long-term administration of estrogen to SD rats resulted in the development of E2-PRLomas, some of which included multi-hormone producing nodules. We herein report results of histopathological analyses of these lesions. PRLoma models were created in female SD rats by 22 weeks or longer administration of a controlled-release preparation of estradiol at a dose of 10 mg/kg/2 weeks. Ten of the 11 PRLoma model rats had proliferative nodular lesions composed of large eosinophilic cells like gonadotrophs inside the PRLoma. These lesions were positive for PRL, TSHβ, and α subunits and were negative for GH, LHβ, ACTH, and S-100. Double immunostaining revealed that these large eosinophilic cells showed coexpression of PRL and TSHβ, PRL and α subunits, and TSHβ and α subunits. Those results clarified that long-term estrogen administration to female SD rats induced multi-hormone producing neoplastic pituitary nodules that expressed PRL, TSHβ, and α subunits. We studied these neoplastic nodules obtained by laser microdissection to acquire findings similar to those of the immunohistochemical analysis. We consider that this animal model is useful for pathogenesis analyses and therapeutic agent development concerning human multi-hormone producing pituitary adenomas

  16. Garcinol sensitizes human head and neck carcinoma to cisplatin in a xenograft mouse model despite downregulation of proliferative biomarkers.

    Science.gov (United States)

    Li, Feng; Shanmugam, Muthu K; Siveen, Kodappully Sivaraman; Wang, Fan; Ong, Tina H; Loo, Ser Yue; Swamy, Mahadeva M M; Mandal, Somnath; Kumar, Alan Prem; Goh, Boon Cher; Kundu, Tapas; Ahn, Kwang Seok; Wang, Ling Zhi; Hui, Kam Man; Sethi, Gautam

    2015-03-10

    Platinum compounds such as cisplatin and carboplatin are frequently used as the first-line chemotherapy for the treatment of the head and neck squamous cell carcinoma (HNSCC). In the present study, we investigated whether garcinol, a polyisoprenylated benzophenone can chemosensitize HNSCC to cisplatin. We found that garcinol inhibited the viability of a panel of diverse HNSCC cell lines, enhanced the apoptotic effect of cisplatin, suppressed constitutive as well as cisplatin-induced NF-κB activation, and downregulated the expression of various oncogenic gene products (cyclin D1, Bcl-2, survivin and VEGF). In vivo study showed that administration of garcinol alone (0.5 mg/kg body weight, i.p. five times/week) significantly suppressed the growth of the tumor, and this effect was further increased by cisplatin. Both the markers of proliferation index (Ki-67) and microvessel density (CD31) were downregulated in tumor tissues by the combination of cisplatin and garcinol. The pharmacokinetic results of garcinol indicated that good systemic exposure was achievable after i.p. administration of garcinol at 0.5 mg/kg and 2 mg/kg with mean peak concentration (Cmax) of 1825.4 and 6635.7 nM in the mouse serum, respectively. Overall, our results suggest that garcinol can indeed potentiate the effects of cisplatin by negative regulation of various inflammatory and proliferative biomarkers. PMID:25762616

  17. Role of connexin 43 in the mechanism of action of alendronate: dissociation of anti-apoptotic and proliferative signaling pathways.

    Science.gov (United States)

    Lezcano, V; Bellido, T; Plotkin, L I; Boland, R; Morelli, S

    2012-02-15

    Bisphosphonates (BPs) inhibit osteocyte and osteoblast apoptosis via opening of connexin (Cx) 43 hemichannels and activating the extracellular signal regulated kinases ERKs. Previously, we hypothesized that intracellular survival signaling is initiated by interaction of BPs with Cx43. However, using whole cell binding assays with [(3)H]-alendronate, herein we demonstrated the presence of saturable, specific and high affinity binding sites in the Cx43-expressing ROS 17/2.8 osteoblastic cells, authentic osteoblasts and MLO-Y4 cells expressing Cx43 or not, as well as in HeLa cells lacking Cx43 expression and ROS 17/2.8 cells pretreated with agents that disassemble Cx channels. In addition, both BPs and the PTP inhibitor Na(3)VO(4) increased proliferation of cells expressing Cx43 or not. Furthermore, although BPs are internalized and inhibit intracellular enzymes in osteoclasts, whether the drugs penetrate non-resorptive bone cells is not known. To clarify this, we evaluated the osteoblastic uptake of AF-ALN, a fluorescently labeled analog of alendronate. AF-ALN was rapidly internalized in cells expressing Cx43 or not indicating that this process is not mediated via Cx43 hemichannels. Altogether, these findings suggest that although required for triggering intracellular survival signaling by BPs, Cx43 is dispensable for cellular BP binding, its uptake, as well as the proliferative effects of these agents. PMID:22230328

  18. Proliferative Vitreoretinopathy after Eye Injuries: An Overexpression of Growth Factors and Cytokines Leading to a Retinal Keloid

    Directory of Open Access Journals (Sweden)

    Francesco Morescalchi

    2013-01-01

    Full Text Available Eye injury is a significant disabling worldwide health problem. Proliferative Vitreoretinopathy (PVR is a common complication that develops in up to 40–60% of patients with an open-globe injury. Our knowledge about the pathogenesis of PVR has improved in the last decades. It seems that the introduction of immune cells into the vitreous, like in penetrating ocular trauma, triggers the production of growth factors and cytokines that come in contact with intra-retinal cells, like Müller cells and RPE cells. Growth factors and cytokines drive the cellular responses leading to PVR’s development. Knowledge of the pathobiological and pathophysiological mechanisms involved in posttraumatic PVR is increasing the possibilities of management, and it is hoped that in the future our treatment strategies will evolve, in particular adopting a multidrug approach, and become even more effective in vision recovery. This paper reviews the current literature and clinical trial data on the pathogenesis of PVR and its correlation with ocular trauma and describes the biochemical/molecular events that will be fundamental for the development of novel treatment strategies. This literature review included PubMed articles published from 1979 through 2013. Only studies written in English were included.

  19. Inhibition of p38/CREB phosphorylation and COX-2 expression by olive oil polyphenols underlies their anti-proliferative effects

    International Nuclear Information System (INIS)

    We investigated the anti-proliferative effects of an olive oil polyphenolic extract on human colon adenocarcinoma cells. Analysis indicated that the extract contained hydroxytyrosol, tyrosol and the various secoiridoid derivatives, including oleuropein. This extract exerted a strong inhibitory effect on cancer cell proliferation, which was linked to the induction of a G2/M phase cell cycle block. Following treatment with the extract (50 μg/ml) the number of cells in the G2/M phase increased to 51.82 ± 2.69% relative to control cells (15.1 ± 2.5%). This G2/M block was mediated by the ability of olive oil polyphenols (50 μg/ml) to exert rapid inhibition of p38 (38.7 ± 4.7%) and CREB (28.6 ± 5.5%) phosphorylation which led to a downstream reduction in COX-2 expression (56.9 ± 9.3%). Our data suggest that olive oil polyphenols may exert chemopreventative effects in the large intestine by interacting with signalling pathways responsible for colorectal cancer development

  20. Differential effects of arsenic on intracellular free calcium levels and the proliferative response of murine mitogen-stimulated lymphocytes

    International Nuclear Information System (INIS)

    This study examined the effects of sodium arsenite treatment on free [Ca2+]i and cell death in mitogen-activated murine lymphocytes. The main findings of this study were that simultaneous sodium arsenite treatment inhibited PHA- but not Con A-induced T cell proliferation, induced a higher increase in free [Ca2+]i and an early increase in the proportion of dead cells in PHA than in Con A activated cells. Sodium arsenite pre-treatment reduced both PHA- and Con A-induced T-cell proliferation. Phorbol myristate ester (PMA) did not prevent the inhibitory effects of both sodium arsenite treatments, suggesting that sodium arsenite did not significantly decreased PKC activation or that its effects occurred on events parallel to PKC activation. Both PHA and Con A increased free [Ca2+]i after stimulation, yet the effect was more pronounced in mitogen-activated cells simultaneously treated with sodium arsenite and particularly in those activated with PHA. The increase in free [Ca2+]i was in agreement with the early cell death induced by sodium arsenite in PHA-activated cells, a finding consistent with the inhibitory effects on PHA-induced proliferation. Sodium arsenite-induced cell death occurred faster in PHA-activated cells. Further studies are needed to ascertain the relationships between the effects of sodium arsenite on free [Ca2+]i levels and the type of cell death induced by sodium arsenite and their relevance for the proliferative response of T cells

  1. Novel triterpenoid saponins from residual seed cake of Camellia oleifera Abel. show anti-proliferative activity against tumor cells.

    Science.gov (United States)

    Zong, Jianfa; Wang, Ruilong; Bao, Guanhu; Ling, Tiejun; Zhang, Liang; Zhang, Xinfu; Hou, Ruyan

    2015-07-01

    Four oleanane-type triterpenoid saponins were isolated from the seed cake of Camellia oleifera Abel.: camelliasaponin B1 and three new saponins, oleiferasaponin C1-C3 (1-3). Their structures were identified as 22-O-angeloyl-camelliagenin B 3-O-[β-d-galactopyranosyl-(1→2)]-[β-d-galactopyranosyl-(1→2)-α-l-arabinopyranosyl-(1→3)]-β-d-glucopyranosiduronic acid methyl ester (1); 22-O-angeloyl-camelliagenin A 3-O-[β-d-galactopyranosyl-(1→2)]-[β-d-glucopyranosyl-(1→2)-β-d-galactopyranosyl-(1→3)]-β-d-glucopyranosiduronic acid methyl ester (2); and 28-O-cinnamoyl-camelliagenin B 3-O-[β-d-galactopyranosylz-(1→2)] [β-d-galactopyranosyl(1→2)-α-l-arabinopyranosyl-(1→3)]-β-d-glucopyranosiduronic acid methyl ester (3) through 1D and 2D NMR, HR-ESI-MS, as well as GC-MS spectroscopic methods. The anti-proliferative activities of these four compounds were investigated on five human tumor cell lines (BEL-7402, BGC-823, MCF-7, HL-60 and KB). Compounds 1 and 2 and camelliasaponin B1 showed significant cytotoxic activities. PMID:25958771

  2. Malignant Trigeminal Nerve Sheath Tumor and Anaplastic Astrocytoma Collision Tumor with High Proliferative Activity and Tumor Suppressor P53 Expression

    Directory of Open Access Journals (Sweden)

    Maher Kurdi

    2014-01-01

    Full Text Available Background. The synchronous development of two primary brain tumors of distinct cell of origin in close proximity or in contact with each other is extremely rare. We present the first case of collision tumor with two histological distinct tumors. Case Presentation. A 54-year-old woman presented with progressive atypical left facial pain and numbness for 8 months. MRI of the brain showed left middle cranial fossa heterogeneous mass extending into the infratemporal fossa. At surgery, a distinct but intermingled intra- and extradural tumor was demonstrated which was completely removed through left orbitozygomatic-temporal craniotomy. Histopathological examination showed that the tumor had two distinct components: malignant nerve sheath tumor of the trigeminal nerve and temporal lobe anaplastic astrocytoma. Proliferative activity and expressed tumor protein 53 (TP53 gene mutations were demonstrated in both tumors. Conclusions. We describe the first case of malignant trigeminal nerve sheath tumor (MTNST and anaplastic astrocytoma in collision and discuss the possible hypothesis of this rare occurrence. We propose that MTNST, with TP53 mutation, have participated in the formation of anaplastic astrocytoma, or vice versa.

  3. Changes in the proliferative activity of hippocampal neural stem cells from manganismus mice

    Institute of Scientific and Technical Information of China (English)

    Guohe Tan; Boning Yang; Guofu Tan; Bo Liang; Jiangu Gong; Xiaodong Ge; Songchao Guo

    2007-01-01

    BACKGROUND: Manganese neurotoxicity presents in the form of not only extracorticospinal tract injury of central nervous system (CNS), but also learning and memory ability damage. So, the mechanism of manganese neurotoxicity will be further studied from the angle ofhippocampus.OBJECTIVE: To observe the effects of manganism on learning and memory ability and the proliferation of neural stem cells (NSCs) in hippocampus of mouse brains, and analyze whether this effect has dose-dependence.DESIGN: Randomized controlled experiment.SETTING: Department of Human Anatomy, and Department of Industrial Hygiene and Occupational Diseases, Guangxi Medical University.MATERIALS: Twenty-eight male Kunming mice, aged 2 weeks, were involved in this experiment. The involved mice were randomized into 4 groups, with 7 in each: control group, low-dose manganism group,middle-dose manganism group and high-dose manganism group. Manganese chloride was purchased from Shantou Chemicals Factory.METHODS: This experiment was carried out in the Experimental Center for Preclinical Medicine, Guangxi Medical University from November 2005 to August 2006. Mice in the low-, middle- and high-dose manganism groups were intraperitoneally injected with 5, 20 and 50 mg/kg per day manganese chloride, once a day, for 2 weeks successively. Mice in the control group were injected with the same amount of stroke-physiological saline solution. Neurobehavioral detection of all the animals was performed in Morris water maze constantly from the 7th day after the first injection of manganese chloride solution. Learning ability was detected in the place navigation test. Mice were trained for 5 consecutive days with four trials per day. The time to find the platform was latency. Memory ability was detected in spatial probe test. Platform was withdrawn on the following day of place navigation. The mice were placed in the water from a random start in the edge of the pool. The number of times they traversed the plateform

  4. Serum Renalase Levels Correlate with Disease Activity in Lupus Nephritis.

    Directory of Open Access Journals (Sweden)

    Chaojun Qi

    Full Text Available Lupus nephritis (LN is among the most serious complications of systemic lupus erythematosus (SLE, which causes significant morbidity and mortality. Renalase is a novel, kidney-secreted cytokine-like protein that promotes cell survival. Here, we aimed to investigate the relationship of serum renalase levels with LN and its role in the disease progression of LN.For this cross-sectional study, 67 LN patients and 35 healthy controls were enrolled. Seventeen active LN patients who received standard therapies were followed up for six months. Disease activity was determined by the SLE Disease Activity-2000 (SLEDAI-2K scoring system and serum renalase amounts were determined by ELISA. Predictive value of renalase for disease activity was assessed. Furthermore, the expression of renalase in the kidneys of patients and macrophage infiltration was assessed by immunohistochemistry.Serum renalase amounts were significantly higher in LN patients than in healthy controls. Moreover, patients with proliferative LN had more elevated serum renalase levels than Class V LN patients. In proliferative LN patients, serum renalase levels were significantly higher in patients with active LN than those with inactive LN. Serum renalase levels were positively correlated with SLEDAI-2K, 24-h urine protein excretion, ds-DNA and ESR but inversely correlated with serum albumin and C3. Renalase amounts decreased significantly after six-months of standard therapy. The performance of renalase as a marker for diagnosis of active LN was 0.906 with a cutoff value of 66.67 μg/ml. We also observed that the amount of renalase was significantly higher in glomerular of proliferative LN along with the co-expression of macrophages.Serum renalase levels were correlated with disease activity in LN. Serum renalase might serve as a potential indicator for disease activity in LN. The marked increase of glomerular renalase and its association with macrophages suggest that it might play an

  5. Lung Disease

    Science.gov (United States)

    ... ePublications > Our ePublications > Lung disease fact sheet ePublications Lung disease fact sheet This information in Spanish (en ... disease? More information on lung disease What is lung disease? Lung disease refers to disorders that affect ...

  6. Use of Retinalamin at an Early Stage of Treatment of Non-proliferative Diabetic Retinopathy in Children with Type 1 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Malysheva N.А.

    2011-09-01

    Full Text Available The aim of the work is to study the effect of retinalamin on circulatory dynamics and functional state of the retina when treating non-proliferative diabetic retinopathy in children with insulin dependent diabetes mellitus. Materials and Methods. There were included into the study 100 children with signs of diabetic retinopathy: microhemorrhages, capillary network distention. All the patients received standard treatment of type 1 diabetes mellitus: insulin therapy, lipoic acid medications, antioxidants. Conclusion. Retinalamin administration at an early stage of non-proliferative diabetic retinopathy reduces the risk of progression of the complication. According to Doppler sonography of ophthalmic artery, retinalamin has a favourable effect on capillary wall of ophthalmic artery and improves flow properties of blood on the local level. The course of injections of the medication in young children can be halved that is less traumatic and more cost effective.

  7. Role of VDR in anti-proliferative effects of calcitriol in tumor-derived endothelial cells and tumor angiogenesis in vivo

    OpenAIRE

    Chung, Ivy; Han, Guangzhou; Seshadri, Mukund; Gillard, Bryan M.; Yu, Wei-Dong; Barbara A Foster; Trump, Donald L.; Johnson, Candace S.

    2009-01-01

    Calcitriol (1, 25-dihydroxycholecalciferol), the major active form of vitamin D, is anti-proliferative in tumor cells and tumor-derived endothelial cells (TDEC). These actions of calcitriol are mediated at least in part by vitamin D receptor (VDR), which is expressed in many tissues including endothelial cells. To investigate the role of VDR in calcitriol effects on tumor vasculature, we established TRAMP-2 tumors subcutaneously into either VDR wild type (WT) or knockout (KO) mice. Within 30 ...

  8. Proliferative responses and binding properties of hematopoietic cells transfected with low-affinity receptors for leukemia inhibitory factor, oncostatin M, and ciliary neurotrophic factor.

    OpenAIRE

    Gearing, D P; Ziegler, S F; Comeau, M R; Friend, D; Thoma, B; Cosman, D; Park, L.; Mosley, B

    1994-01-01

    Specific low-affinity receptors for leukemia inhibitory factor (LIF), oncostatin M (OSM; gp130), and ciliary neurotrophic factor (CNTF; receptor alpha, CNTFR alpha) may be utilized in various combinations to generate high-affinity binding sites and signal transduction. We have tested the ability of combinations of these receptors to transduce a proliferative signal in BAF-B03 cells. Coexpression of the LIF receptor and gp130 in these cells conferred high-affinity LIF and OSM binding and respo...

  9. Der proliferative und apoptotische in vitro Effekt von Progesteron und sieben synthetischen Gestagenen auf normale Brustdrüsenzellen und primäre Mammakarzinomzellen

    OpenAIRE

    Krämer, Elizabeth

    2007-01-01

    Zielsetzung: Der proliferative und apoptotische Effekt von acht pharmakologisch unterschiedlichen Gestagenen, die bereits zur HRT angewandt oder hierfür überprüft werden, wurden in normalen mit Wachstumsfaktor und / oder Estradiol behandelten MCF10A Brustdrüsenzellen und Östrogenrezeptor positiven HCC1500 Zellen primärer Mammakarzinome untersucht. Verschiedene Apoptosemarker wurden bestimmt. Folgende Gestagene wurden benutzt: natürliches Progesteron (P), sowie die synthetischen Gestagene Chlo...

  10. A case-control study of oral epithelial proliferative markers among Sudanese Toombak dippers using micronuclei assay, argyrophilic nucleolar organizer region, Papanicolaou and crystal violet methods

    OpenAIRE

    Anass M. Abbas; Hussain G. Ahmed

    2013-01-01

    The use of Toombak has been reported to play a major role in the etiology of oral cancer in Sudan. The cellular proliferative activity on the oral epithelium of 210 Toombak dippers was assessed by applying the micronuclei frequency, mean argyrophilic nucleolar organizer region (AgNOR) counts, Papanicolaou method, and 1% crystal violet stain. Participants were divided into 3 groups: 200 were apparently healthy individuals, 100 were Toombak users (cases), 100 were non-tobacco users (control) an...

  11. Experimental and theoretical study of possible correlation between the electrochemistry of canthin-6-one and the anti-proliferative activity against human cancer stem cells

    Science.gov (United States)

    Cebrián-Torrejón, G.; Doménech-Carbó, A.; Scotti, M. T.; Fournet, A.; Figadère, B.; Poupon, E.

    2015-12-01

    This work presents an approach to study the performance of novel targets able to overcome cancer stem cell chemoresistance, based on the voltammetric data for microparticulate films of natural or synthetic alkaloids from the canthin-6-one series. A comparison of this voltammetric technique with conventional solution phase electrochemistry suggests the differences in the anti-proliferative activity of canthin-6-ones could be tentatively correlated to their different capacity to generate semiquinone radical anions. These data also match theoretical calculations.

  12. Differences between the neurogenic and proliferative abilities of Müller glia with stem cell characteristics and the ciliary epithelium from the adult human eye

    OpenAIRE

    Bhatia, Bhairavi; Jayaram, Hari; Singhal, Shweta; Jones, Megan F; Limb, G. Astrid

    2011-01-01

    Much controversy has arisen on the nature and sources of stem cells in the adult human retina. Whilst ciliary epithelium has been thought to constitute a source of neural stem cells, a population of Müller glia in the neural retina has also been shown to exhibit neurogenic characteristics. This study aimed to compare the neurogenic and proliferative abilities between these two major cell populations. It also examined whether differences exist between the pigmented and non-pigmented ciliary ep...

  13. 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)

    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 [3H]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

  14. Elevated Levels of Cytokines Associated with Th2 and Th17 Cells in Vitreous Fluid of Proliferative Diabetic Retinopathy Patients.

    Directory of Open Access Journals (Sweden)

    Masaru Takeuchi

    Full Text Available Macrophages are involved in low-grade inflammation in diabetes, and play pathogenic roles in proliferative diabetic retinopathy (PDR by producing proinflammatory cytokines. T cells as well as other cells are also activated by proinflammatory cytokines, and infiltration into the vitreous of patients with PDR has been shown. In this study, we measured helper T (Th cell-related cytokines in the vitreous of PDR patients to define the characteristics of Th-mediated immune responses associated with PDR. The study group consisted of 25 type 2 diabetic patients (25 eyes with PDR. The control group consisted of 27 patients with epiretinal membrane (ERM, 26 patients with idiopathic macular hole (MH, and 26 patients with uveitis associated with sarcoidosis. Vitreous fluid was obtained at the beginning of vitrectomy, and centrifuging for cellular removals was not performed. Serum was also collected from PDR patients. IL-1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, IFN-γ, soluble sCD40L, and TNFα in the vitreous and serum samples were measured. Both percent detectable and levels of IL-4, IL-6, IL-17A, IL-21, IL-22, and TNFα in the vitreous were significantly higher than those in the serum in PDR patients. Vitreous levels of these cytokines and IL-31 were significantly higher in PDR than in ERM or MH patients. Vitreous levels of IL-4, IL-17A, IL-22, IL-31, and TNFα in PDR patients were also significantly higher than those of sarcoidosis patients. In PDR patients, vitreous IL-17A level correlated significantly with vitreous levels of IL-22 and IL-31, and especially with IL-4 and TNFα. Although it is unclear whether these cytokines play facilitative roles or inhibitory roles for the progression of PDR, the present study indicated that Th2- and Th17-related immune responses are involved in the pathogenesis of PDR.

  15. miR-203 inhibits melanoma invasive and proliferative abilities by targeting the polycomb group gene BMI1

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Xiao [Department of Dermatology and Venereal Disease, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Sun, Yong [Department of Burn and Plastic Surgery, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an 223300 (China); Han, Siqi [Department of Medical Oncology, Jinling Hospital, Nanjing 210002 (China); Zhu, Wei [Department of Dermatology and Venereal Disease, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Zhang, Haiping, E-mail: zhanghaiping_2000@163.com [Department of Dermatology and Venereal Disease, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Lian, Shi, E-mail: lianshi_2020@163.com [Department of Dermatology and Venereal Disease, Capital Medical University, Beijing 100069 (China)

    2015-01-02

    Highlights: • First reported deregulation of miR-203 and up-regulation of BMI1 in metastatic melanoma. • miR-203 decreased BMI1 expression by directly binding to 3′UTR. • Further found miR-203 overexpression suppressed cell invasion and stemness. • Re-expression of BMI1 rescued miR-203-mediated suppression. • miR-203-BMI1 axis may be potential therapeutic targets of melanoma metastasis. - Abstract: Metastasis is the major problem in malignant melanoma, posing a therapeutic challenge to clinicians. The investigation of the underlying mechanism driving this progress remains a large unmet need. In this study, we revealed a miR-203-BMI1 axis that regulated melanoma metastasis. We found significantly deregulation of miR-203 and up-regulation of BMI1 in melanoma, particularly in metastatic melanoma. An inverse correlation between the levels of miR-203 and BMI1 was further observed in melanoma tissues and cell lines. We also identified BMI1 as a downstream target gene of miR-203, which bound to the 3′UTR of BMI1. Overexpression of miR-203 was associated with decreased BMI1 expression and impaired cell invasion and tumor sphere formation activities. Re-expression of BMI1 markedly rescued miR-203-mediated suppression of these events. Taken together, our results demonstrated that miR-203 regulated melanoma invasive and proliferative abilities in part by targeting BMI1, providing new insights into potential mechanisms of melanoma metastasis.

  16. miR-203 inhibits melanoma invasive and proliferative abilities by targeting the polycomb group gene BMI1

    International Nuclear Information System (INIS)

    Highlights: • First reported deregulation of miR-203 and up-regulation of BMI1 in metastatic melanoma. • miR-203 decreased BMI1 expression by directly binding to 3′UTR. • Further found miR-203 overexpression suppressed cell invasion and stemness. • Re-expression of BMI1 rescued miR-203-mediated suppression. • miR-203-BMI1 axis may be potential therapeutic targets of melanoma metastasis. - Abstract: Metastasis is the major problem in malignant melanoma, posing a therapeutic challenge to clinicians. The investigation of the underlying mechanism driving this progress remains a large unmet need. In this study, we revealed a miR-203-BMI1 axis that regulated melanoma metastasis. We found significantly deregulation of miR-203 and up-regulation of BMI1 in melanoma, particularly in metastatic melanoma. An inverse correlation between the levels of miR-203 and BMI1 was further observed in melanoma tissues and cell lines. We also identified BMI1 as a downstream target gene of miR-203, which bound to the 3′UTR of BMI1. Overexpression of miR-203 was associated with decreased BMI1 expression and impaired cell invasion and tumor sphere formation activities. Re-expression of BMI1 markedly rescued miR-203-mediated suppression of these events. Taken together, our results demonstrated that miR-203 regulated melanoma invasive and proliferative abilities in part by targeting BMI1, providing new insights into potential mechanisms of melanoma metastasis

  17. Post-proliferative immature radial glial cells female-specifically express aromatase in the medaka optic tectum.

    Directory of Open Access Journals (Sweden)

    Akio Takeuchi

    Full Text Available Aromatase, the key enzyme responsible for estrogen biosynthesis, is present in the brain of all vertebrates. Much evidence has accumulated that aromatase is highly and exclusively expressed in proliferating mature radial glial cells in the brain of teleost fish even in adulthood, unlike in other vertebrates. However, the physiological significance of this expression remains unknown. We recently found that aromatase is female-specifically expressed in the optic tectum of adult medaka fish. In the present study, we demonstrated that, contrary to the accepted view of the teleost brain, female-specific aromatase-expressing cells in the medaka optic tectum represent a transient subset of post-proliferative immature radial glial cells in the neural stem cell lineage. This finding led us to hypothesize that female-specific aromatase expression and consequent estrogen production causes some sex difference in the life cycle of tectal cells. As expected, the female tectum exhibited higher expression of genes indicative of cell proliferation and radial glial maturation and lower expression of an anti-apoptotic gene than did the male tectum, suggesting a female-biased acceleration of the cell life cycle. Complicating the interpretation of this result, however, is the additional observation that estrogen administration masculinized the expression of these genes in the optic tectum, while simultaneously stimulating aromatase expression. Taken together, these results provide evidence that a unique subpopulation of neural stem cells female-specifically express aromatase in the optic tectum and suggest that this aromatase expression and resultant estrogen synthesis have an impact on the life cycle of tectal cells, whether stimulatory or inhibitory.

  18. 1. modification of the proliferative capacity of transplanted bone marrow colony forming units by changes in the host environment

    International Nuclear Information System (INIS)

    Regulation of the proliferation of transplanted colony forming units (CFUs) was investigated in lethally irradiated mice, pretreated by methods known to accelerate hemopoietic recovery after sublethal irradiation. Prospective recipients were exposed to either hypoxia, vinblastine or priming irradiation and at different intervals thereafter lethally irradiated and transplanted with bone marrow. Repopulation of CFUs was determined by counting the number of splenic colonies in primary recipients or by retransplantation. Regeneration of grafted CFUs was greatly accelerated and their self-renewal capacity increased in mice grafted within 2 days after hypoxia. Also the number of splenic colonies formed by grafted syngeneic CFUs as well as by C57B1 parent CFUs growing in BC3F1 hosts was significantly increased. The effect was not dependent on the seeding efficiency of CFUs and apparently resulted from hypoxia induced changes in the hosts' physiological environment. Proliferative capacity of grafted CFUs increased remarkably in hosts receiving vinblastine 2 or 4 days prior to irradiation. Priming irradiation given 6 days before main irradiation accelerated, given 2 days before impaired regeneration of CFUs. The increased rate of regeneration was not related to the cellularity of hemopoietic organs at the time of transplantation. The growth of CFUs in diffusion chambers implanted into posthypoxic mice was only slightly improved which does indicate that the accelerated regeneration of CFUs in posthypoxic mice is mainly due to the changes in the hemopoietic microenvironment. A short conditioning of transplanted CFUs by host factor(s) was sufficient to improve regeneration. The results might suggest that the speed of hemopoietic regeneration depends on the number of CFUs being induced to proliferate shortly after irradiation, rather than on the absolute numbers of CFUs available to the organism. (author)

  19. Spectral domain ocular coherence tomography findings pre- and post vitrectomy with fibrovascular membrane delamination for proliferative diabetic retinopathy.

    Science.gov (United States)

    Dooley, I; Laviers, H; Papavasileiou, E; Mckechnie, C; Zambarakji, H

    2016-01-01

    PurposeTo describe the intraretinal microstructure using serial spectral domain optical coherence tomography (SD-OCT) preceding and following pars plana vitrectomy and delamination of fibrovascular membranes in patients with proliferative diabetic retinopathy (PDR).MethodsThis retrospective, interventional case series includes 28 eyes. Outcome measures included LogMAR distance best-corrected visual acuity (BCVA), SD-OCT integrity of photoreceptor inner and outer segments junction (IS/OS), and integrity of external limiting membrane (ELM).ResultsPre-operative central macular thickness (CMT) was significantly correlated with the final post-operative LogMAR BCVA (Pearson's coefficient r=0.89; P=0.001). The eyes were categorised into three groups based on post-operative IS/OS integrity (group 0: IS/OS intact; group 1: IS/OS irregular but not completely disrupted; group 2: IS/OS completely disrupted). Mean BCVA improved significantly in group 0 (n=9) from 1.13±0.75 preoperatively to 0.34±0.21 (Student's t-test: P=0.06), in group 1 (n=10) the BCVA improved from 0.88±0.56 to 0.58±0.31 (Student's t-test: P=0.053) and in group 2 (n=9) the BCVA improved from 1.64±0.53 to 1.53±0.75 (Student's t-test: P=0.652).IS/OS integrity and ELM integrity at 3 months post operatively, were significantly and positively correlated with final BCVA (Pearson's coefficient: r=0.83, PCMT and post-operative disruption of the IS/OS and ELM are useful prognostic indicators in fibrovascular delamination surgery for patients with PDR. PMID:26403326

  20. Caveolin-1 is critical in the proliferative effect of leptin on osteoblasts through the activation of Akt.

    Science.gov (United States)

    Zou, Lin; Zhang, Guichun; Liu, Lifeng; Chen, Chen; Cao, Xuecheng; Cai, Jinfang

    2016-09-01

    Osteoblasts are critical in bone remodeling and the repair of bone fractures. Leptin is involved in bone metabolism and osteoblast survival through the downstream signaling pathway, however, the exact mechanism of the effect of leptin on osteoblasts remains to be fully elucidated. In the present study, hFOB 1.19 cells were used to observe the effects of leptin on cell proliferation and apoptosis, and to investigate the underlying mechanism. The results confirmed that treatment of hFOB 1.19 cells with leptin significantly induced cell proliferation. Western blot analysis showed that the expression of caveolin‑1 and the activation of Akt in the cells treated with leptin were significantly increased, compared with the control cells. Additionally, inhibiting Akt activation eliminated the effects on cell proliferation induced by leptin. The rates of cell apoptosis and cell cycle distribution were examined using flow cytometry, which revealed a decrease in the apoptotic rate and an increase in the proportion of cells in the S phase. This indicated that leptin was capable of inducing cell proliferation by inhibiting apoptosis and stimulating cell progression to the S phase. Transfection of the cells with caveolin‑1 small interfering RNA showed that the activation of Akt induced by leptin was significantly inhibited. Furthermore, caveolin‑1 knockdown and inhibiting Akt activation eliminated the increased proliferation, increased proportion of cells in the S phase and increased anti‑apoptotic effects induced by leptin. Taken together, the data obtained in the present study demonstrated that caveolin‑1 was critical in the proliferative effect of leptin on osteoblasts via the activation of Akt. PMID:27430651

  1. Myofibroblasts in proliferative diabetic retinopathy can originate from infiltrating fibrocytes and through endothelial-to-mesenchymal transition (EndoMT).

    Science.gov (United States)

    Abu El-Asrar, Ahmed M; De Hertogh, Gert; van den Eynde, Kathleen; Alam, Kaiser; Van Raemdonck, Katrien; Opdenakker, Ghislain; Van Damme, Jo; Geboes, Karel; Struyf, Sofie

    2015-03-01

    Myofibroblasts expressing α-smooth muscle actin (α-SMA) are the key cellular mediator of fibrosis. Fibrovascular epiretinal membranes from patients with proliferative diabetic retinopathy (PDR) are characterized by the accumulation of a large number of myofibroblasts. We explored the hypothesis that proliferating endothelial cells via endothelial-to-mesenchymal transition (EndoMT) and/or bone marrow-derived circulating fibrocytes contribute to the myofibroblast population present in PDR epiretinal membranes. Epiretinal membranes from 14 patients with PDR were studied by immunohistochemistry. All membranes contained neovessels expressing the endothelial cell marker CD31. CD31(+) endothelial cells co-expressed the fibroblast/myofibroblast markers fibroblast-specific protein-1 (FSP-1) and α-SMA, indicative for the occurrence of endoMT. In the stroma, cells expressing FSP-1, α-SMA, the leukocyte common antigen CD45, and the myelomonocytic marker CD11b were detected. Double labeling showed co-localization of CD45 with FSP-1 and α-SMA and co-localization of CD11b with α-SMA and matrix metalloproteinase-9, demonstrating the presence of infiltrating fibrocytes. In addition, we investigated the phenotypic changes that take place in human retinal microvascular endothelial cells following exposure to transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF) and the proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Retinal microvascular endothelial cells changed morphology upon cytokine exposure, lost the expression of endothelial cell markers (endothelial nitric oxide synthase and vascular endothelial-cadherin) and started to express mesenchymal markers (calponin, snail, transgelin and FSP-1). These results suggest that endothelial cells as well as circulating fibrocytes may differentiate into myofibroblasts in the diabetic eye and contribute to pathologic fibrosis in PDR. PMID:25637870

  2. Influence of constant, alternating and cyclotron low-intensity electromagnetic fields on fibroblast proliferative activity in vitro

    Directory of Open Access Journals (Sweden)

    Kalinin, Andrey

    2009-12-01

    Full Text Available Available data allow assuming the presence of stimulation of reparative processes under influence of low-intensity electromagnetic field, commensurable with a magnetic field of the Earth. Research of effects of low-intensity electromagnetic fields on fibroblast proliferative activity in human lungs in cell culture was performed. The influence of a constant electromagnetic field, an alternating electromagnetic field by frequency of 50 Hz and cyclotron electromagnetic field with identical intensity for all kinds of fields – 80 mcTl – on value of cellular mass and a correlation of live and dead cells in culture is investigated in three series of experiments. We used the universal electromagnetic radiator generating all three kinds of fields and supplied by a magnetometer which allows measuring the intensity of accurate within 0.1 mcTl including taking into account the Earth’s magnetic field intensity. The peak value for stimulation cellular proliferation in the present experiences was two-hour influence by any of the specified kinds of electromagnetic fields. The irradiation by cyclotron electromagnetic field conducts positive dynamics in growth of live cells (up to 206±22% and decreases the number of dead cells (down to 31±6%. Application of cyclotron magnetic fields promoted creation of optimum conditions for proliferation. As a result of researches we observed the reliable 30% increase of nitro-tetrazolium index (in nitro-tetrazolium blue test after irradiation by cyclotron electromagnetic field in experience that testifies to strengthening of the cell breathing of living cells.In our opinion, it is necessary to pay attention not only to a pure gain of cells, but also to reduction of number dead cells that can be criterion of creation of optimum conditions for their specific development and valuable functioning.

  3. Valved versus nonvalved cannula small-gauge pars plana vitrectomy for repair of retinal detachments with Grade C proliferative vitreoretinopathy

    Directory of Open Access Journals (Sweden)

    Oellers P

    2016-05-01

    Full Text Available Patrick Oellers, Sandra Stinnett, Paul Hahn Duke Eye Center, Duke University School of Medicine, Durham, NC, USA Purpose: Valved cannulas are a recent addition to small-gauge pars plana vitrectomy (PPV and provide stable intraocular fluidics. The goal of this study was to compare outcomes and postoperative complication rates of valved vs nonvalved cannula small-gauge PPV for repair of retinal detachments (RDs complicated by Grade C proliferative vitreoretinopathy (PVR.Methods: A retrospective chart review of 364 consecutive eyes with either valved or nonvalved cannula PPV for RD repair was performed. The primary outcomes were single surgery and final anatomic success and change in best-corrected visual acuity for repair of RDs complicated by Grade C PVR.Results: We identified 36 eyes in the valved group and 31 eyes in the nonvalved group with Grade C PVR RD. The single surgery success was 83% vs 77% (P=0.555 and the final anatomic success was 94% vs 87% (P=0.404 in the valved vs nonvalved eyes, respectively. The mean final visual acuity gain was −0.36 logarithm of the minimum angle of resolution (logMAR; approximate Early Treatment Diabetes Retinopathy Study [ETDRS] score =17 letters in valved eyes vs −0.33 logMAR (approximate ETDRS score =16 letters in nonvalved eyes (P=0.81. Postoperative complication rates including postoperative day 1 hypotony, hypertony, and anterior chamber fibrin formation; postoperative retention of intraocular or subretinal perfluorocarbon liquid; and subsequent epiretinal membrane peel were not statistically different between groups.Conclusion: Valved cannula PPV yields equivalent visual acuity and anatomic outcomes without increased postoperative complication rates compared to traditional nonvalved cannula PPV for Grade C PVR-associated RD repair. Keywords: 23 gauge, 25 gauge, PVR, RD, chronic, single surgery success, final anatomic success

  4. MicroRNA mir-16 is anti-proliferative in enterocytes and exhibits diurnal rhythmicity in intestinal crypts

    Energy Technology Data Exchange (ETDEWEB)

    Balakrishnan, Anita, E-mail: anita.balakrishnan@doctors.org.uk [Department of Surgery, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Department of Surgery, Harvard Medical School, Boston, MA 02115 (United States); School of Clinical Sciences, Division of Gastroenterology, University of Liverpool, Liverpool L69 3GE (United Kingdom); Stearns, Adam T. [Department of Surgery, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Department of Surgery, Harvard Medical School, Boston, MA 02115 (United States); Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 2JD (United Kingdom); Park, Peter J. [Department of Medicine, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Harvard Medical School, Center for Biomedical Informatics, Boston, MA 02115 (United States); Dreyfuss, Jonathan M. [Department of Medicine, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Ashley, Stanley W. [Department of Surgery, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Department of Surgery, Harvard Medical School, Boston, MA 02115 (United States); Rhoads, David B. [Department of Surgery, Harvard Medical School, Boston, MA 02115 (United States); Pediatric Endocrine Unit, MassGeneral Hospital for Children, Boston, MA 02114 (United States); Tavakkolizadeh, Ali, E-mail: atavakkoli@partners.org [Department of Surgery, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Department of Surgery, Harvard Medical School, Boston, MA 02115 (United States)

    2010-12-10

    Background and aims: The intestine exhibits profound diurnal rhythms in function and morphology, in part due to changes in enterocyte proliferation. The regulatory mechanisms behind these rhythms remain largely unknown. We hypothesized that microRNAs are involved in mediating these rhythms, and studied the role of microRNAs specifically in modulating intestinal proliferation. Methods: Diurnal rhythmicity of microRNAs in rat jejunum was analyzed by microarrays and validated by qPCR. Temporal expression of diurnally rhythmic mir-16 was further quantified in intestinal crypts, villi, and smooth muscle using laser capture microdissection and qPCR. Morphological changes in rat jejunum were assessed by histology and proliferation by immunostaining for bromodeoxyuridine. In IEC-6 cells stably overexpressing mir-16, proliferation was assessed by cell counting and MTS assay, cell cycle progression and apoptosis by flow cytometry, and cell cycle gene expression by qPCR and immunoblotting. Results: mir-16 peaked 6 hours after light onset (HALO 6) with diurnal changes restricted to crypts. Crypt depth and villus height peaked at HALO 13-14 in antiphase to mir-16. Overexpression of mir-16 in IEC-6 cells suppressed specific G1/S regulators (cyclins D1-3, cyclin E1 and cyclin-dependent kinase 6) and produced G1 arrest. Protein expression of these genes exhibited diurnal rhythmicity in rat jejunum, peaking between HALO 11 and 17 in antiphase to mir-16. Conclusions: This is the first report of circadian rhythmicity of specific microRNAs in rat jejunum. Our data provide a link between anti-proliferative mir-16 and the intestinal proliferation rhythm and point to mir-16 as an important regulator of proliferation in jejunal crypts. This function may be essential to match proliferation and absorptive capacity with nutrient availability.

  5. Extended follow-up of the CYCLOFA-LUNE trial comparing two sequential induction and maintenance treatment regimens for proliferative lupus nephritis based either on cyclophosphamide or on cyclosporine A.

    Science.gov (United States)

    Závada, J; Sinikka Pesicková, S; Rysavá, R; Horák, P; Hrncír, Z; Lukác, J; Rovensky, J; Vítová, J; Havrda, M; Rychlík, I; Böhmova, J; Vlasáková, V; Slatinská, J; Zadrazil, J; Olejárová, M; Tegzova, D; Tesar, V

    2014-01-01

    Objective To evaluate the extended follow-up of the CYCLOFA-LUNE trial, a randomized prospective trial comparing two sequential induction and maintenance treatment regimens for proliferative lupus nephritis based either on cyclophosphamide (CPH) or cyclosporine A (CyA). Patients and methods Data for kidney function and adverse events were collected by a cross-sectional survey for 38 of 40 patients initially randomized in the CYCLOFA-LUNE trial. Results The median follow-up time was 7.7 years (range 5.0-10.3). Rates of renal impairment and end-stage renal disease, adverse events (death, cardiovascular event, tumor, premature menopause) did not differ between the CPH and CyA group, nor did mean serum creatinine, 24 h proteinuria and SLICC damage score at last follow-up. Most patients in both groups were still treated with glucocorticoids, other immunosuppressant agents and blood pressure lowering drugs. Conclusion An immunosuppressive regimen based on CyA achieved similar clinical results to that based on CPH in the very long term. PMID:24213308

  6. The analysis of risk factors of proliferative diabetic retinopathy%增殖性糖尿病视网膜病变的危险因素分析

    Institute of Scientific and Technical Information of China (English)

    胡安娣娜; 李涛; 罗燕; 丁小燕; 朱晓波; 李士清; 余洪华; 唐仕波

    2011-01-01

    Objective To investigate the risk factors of proliferative diabetic retinopathy (PDR) in type 2 diabetes mellitus (DM) patients of 10 years or more duration in Guangdong province. Methods A total of 144 type 2 DM of 10 years or more duration from Zhongshan Ophthalmic Center and the Department of Endocrinology of the First Affiliated Hospital of Sun Yat-sen University were divided into PDR group and non-proliferative diabetic retinopathy (NPDR) group, and then investigated by case-control study. To analyze the factors associated with PDR from the factors of demographic characteristics, behavioral habits, past disease history, diabetes family history, blood pressure and glycated hemoglobin by X 2 test and multivariate logistic regression analysis. Results Univariate analysis showed that younger age (OR=0.25, P=0.000), lower educated (OR=2.42, P=0.013), diabetic nephropathy (OR=2.80, P=0.01), diabetic peripheral neuropathy (DPN) (OR=2.56, P=0.008), less exercise (OR=2.55, P=0.006), hypertension (OR=2.31, P=0.014) and smoking (OR=3.96, P=0.001) were associated with PDR. Multivariate logistic regression analysis showed younger age (OR=0.92, P=0.000), lower educated (OR=2.64, P=0.021), DPN (OR=2.36, P=0.036) and smoking (OR=3.27, P=0.013) were associated with PDR. Conclusions Young age, low education, smoking and DPN are the risk factors of PDR in type 2 DM patients of 10 years or more duration. Ophthalmologists should follow up DM patients of young age, less educated, smoking and DPN frequently and let patients pay more attention to lifestyle.%目的 探讨广东地区病程10年及以上的2型糖尿病(DM)患者发生增殖性糖尿病视网膜病变( PDR)的危险因素。方法 收集中山大学中山眼科中心和中山大学附属第一医院内分泌科就诊的144例病程10年及以上的2型DM患者,分为PDR组和非增殖性糖尿病视网膜病变(NPDR)组,进行病例对照研究。通过x2检验及多因素logistic回归分析人群特征、生活

  7. Lyme disease in the differential diagnosis of rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Ahmet Karadağ

    2016-03-01

    Full Text Available Clinically, there are some differences between rheumatoid arthritis (RA and Lyme disease. Although Lyme arthritis exhibits marked differences from RA, it can cause erosion at joint due to chronic proliferative synovitis as similar to RA. In the literature, a case was reported where both entities were seen together. In this manuscript, we aimed to present a case with symmetric arthritis at small hand joints and arthralgia at wrist that mimicked RA but diagnosed as Lyme disease by history, clinical presentation and laboratory findings, and successfully treated.

  8. Arsenic

    Science.gov (United States)

    ... of countries, including Argentina, Bangladesh, Chile, China, India, Mexico, and the United States of America. Drinking-water, ... ingestion of inorganic arsenic include developmental effects, neurotoxicity, diabetes, pulmonary disease and cardiovascular disease. Arsenic-induced myocardial ...

  9. Oral squamous cell carcinoma proliferative phenotype is modulated by proanthocyanidins: a potential prevention and treatment alternative for oral cancer

    Directory of Open Access Journals (Sweden)

    Swapp Aaron

    2007-06-01

    Full Text Available Abstract Background Despite the recently reported drop in the overall death rate from cancer, the estimated survival rate and number of deaths from oral cancer remain virtually unchanged. Early detection efforts, in combination with strategies for prevention and risk-reduction, have the potential to dramatically improve clinical outcomes. The identification of non-toxic, effective treatments, including complementary and alternative therapies, is critical if the survival rate is to be improved. Epidemiologic studies have suggested a protective effect from certain plant-derived foods and extracts; however, it has been difficult to isolate and identify the compounds most responsible for these observations. The primary purpose of this study was to investigate the response of human oral squamous cell carcinoma (OSCC to proanthocyanidin (PAC, a plant-derived compound that may inhibit the progression of several other cancers. Methods Using a series of in vitro assays, we sought to quantify the effects of PAC on OSCC, cervical carcinoma, and non-cancerous cell lines, specifically the effects of PAC on cell proliferation. Recent data suggest that infection with the human papillomavirus (HPV may also modulate the proliferative potential of OSCC; therefore, we also measured the effects of PAC administration on HPV-transfected OSCC proliferation. Results Our results demonstrated that PAC administration was sufficient to significantly suppress cellular proliferation of OSCC in a dose-dependent manner. In addition, the increased proliferation of OSCC after transfection with HPV 16 was reduced by the administration of PAC, as was the proliferation of the cervical cancer and non-cancerous cell lines tested. Our results also provide preliminary evidence that PAC administration may induce apoptosis in cervical and oral cancer cell lines, while acting merely to suppress proliferation of the normal cell line control. Conclusion These results signify that PAC may be

  10. Medium Renewal Blocks Anti-Proliferative Effects of Metformin in Cultured MDA-MB-231 Breast Cancer Cells.

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    Maruša Rajh

    Full Text Available Epidemiological studies indicate that metformin, a widely used type 2 diabetes drug, might reduce breast cancer risk and mortality in patients with type 2 diabetes. Metformin might protect against breast cancer indirectly by ameliorating systemic glucose homeostasis. Alternatively, it might target breast cancer cells directly. However, experiments using MDA-MB-231 cells, a standard in vitro breast cancer model, produced inconsistent results regarding effectiveness of metformin as a direct anti-cancer agent. Metformin treatments in cultured MDA-MB-231 cells are usually performed for 48-96 hours, but protocols describing renewal of cell culture medium during these prolonged treatments are rarely reported. We determined whether medium renewal protocol might alter sensitivity of MDA-MB-231 cells treated with metformin. Using the MTS assay, BrdU incorporation and Hoechst staining we found that treatment with metformin for 48-72 hours failed to suppress viability and proliferation of MDA-MB-231 cells if low-glucose (1 g/L medium was renewed every 24 hours. Conversely, metformin suppressed their viability and proliferation if medium was not renewed. Without renewal glucose concentration in the medium was reduced to 0.1 g/L in 72 hours, which likely explains increased sensitivity to metformin under these conditions. We also examined whether 2-deoxy-D-glucose (2-DG reduces resistance to metformin. In the presence of 2-DG metformin reduced viability and proliferation of MDA-MB-231 cells with or without medium renewal, thus demonstrating that 2-DG reduces their resistance to metformin. In sum, we show that medium renewal blocks anti-proliferative effects of metformin during prolonged treatments in low-glucose medium. Differences in medium renewal protocols during prolonged treatments might therefore lead to apparently inconsistent results as regards effectiveness of metformin as a direct anti-cancer agent. Finally, our results indicate that co-therapy with

  11. Medium Renewal Blocks Anti-Proliferative Effects of Metformin in Cultured MDA-MB-231 Breast Cancer Cells.

    Science.gov (United States)

    Rajh, Maruša; Dolinar, Klemen; Miš, Katarina; Pavlin, Mojca; Pirkmajer, Sergej

    2016-01-01

    Epidemiological studies indicate that metformin, a widely used type 2 diabetes drug, might reduce breast cancer risk and mortality in patients with type 2 diabetes. Metformin might protect against breast cancer indirectly by ameliorating systemic glucose homeostasis. Alternatively, it might target breast cancer cells directly. However, experiments using MDA-MB-231 cells, a standard in vitro breast cancer model, produced inconsistent results regarding effectiveness of metformin as a direct anti-cancer agent. Metformin treatments in cultured MDA-MB-231 cells are usually performed for 48-96 hours, but protocols describing renewal of cell culture medium during these prolonged treatments are rarely reported. We determined whether medium renewal protocol might alter sensitivity of MDA-MB-231 cells treated with metformin. Using the MTS assay, BrdU incorporation and Hoechst staining we found that treatment with metformin for 48-72 hours failed to suppress viability and proliferation of MDA-MB-231 cells if low-glucose (1 g/L) medium was renewed every 24 hours. Conversely, metformin suppressed their viability and proliferation if medium was not renewed. Without renewal glucose concentration in the medium was reduced to 0.1 g/L in 72 hours, which likely explains increased sensitivity to metformin under these conditions. We also examined whether 2-deoxy-D-glucose (2-DG) reduces resistance to metformin. In the presence of 2-DG metformin reduced viability and proliferation of MDA-MB-231 cells with or without medium renewal, thus demonstrating that 2-DG reduces their resistance to metformin. In sum, we show that medium renewal blocks anti-proliferative effects of metformin during prolonged treatments in low-glucose medium. Differences in medium renewal protocols during prolonged treatments might therefore lead to apparently inconsistent results as regards effectiveness of metformin as a direct anti-cancer agent. Finally, our results indicate that co-therapy with 2-DG and

  12. Evaluation of chromosomal abnormalities by clg-FISH and association with proliferative and apoptotic indexes in multiple myeloma

    Energy Technology Data Exchange (ETDEWEB)

    Linardi, C.C.G.; Martinez, G.; Velloso, E.D.R.P.; Leal, A.M.; Kumeda, C.A.; Buccheri, V. [Disciplina de Hematologia e Hemoterapia, Departamento de Clínica Médica, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Azevedo, R.S. [Departamento de Patologia, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Peliçario, L.M.; Dorlhiac-Llacer, P. [Disciplina de Hematologia e Hemoterapia, Departamento de Clínica Médica, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)

    2012-08-24

    Eighty-six newly diagnosed multiple myeloma (MM) patients from a public hospital of São Paulo (Brazil) were evaluated by cIg-FISH for the presence of del(13)(q14), t(4;14)(p16.3;q32) and del(17)(p13). These abnormalities were observed in 46.5, 9.3, and 7.0% of the patients, respectively. In order to identify the possible role of del(13)(q14) in the physiopathology of MM, we investigated the association between this abnormality and the proliferative and apoptotic indexes of plasma cells. When cases demonstrating t(4;14)(p16.3;q32) and del(17)(p13) were excluded from the analysis, we observed a trend towards a positive correlation between the proportion of cells carrying del(13)(q14) and plasma cell proliferation, determined by Ki-67 expression (r = 0.23, P = 0.06). On the other hand, no correlation between the proportion of cells carrying del(13)(q14) and apoptosis, determined by annexin-V staining, was detected (r = 0.05, P = 0.69). In general, patients carrying del(13)(q14) did not have lower survival than patients without del(13)(q14) (P = 0.15), but patients with more than 80% of cells carrying del(13)(q14) showed a lower overall survival (P = 0.033). These results suggest that, when del(13)(q14) is observed in a high proportion of malignant cells, it may have a role in determining MM prognosis. Another finding was a statistically significant lower overall survival of patients with t(4;14)(p16.3;q32) (P = 0.026). In the present study, almost half the patients with t(4;14)(p16.3;q32) died just after diagnosis, before starting treatment. This fact suggests that, in São Paulo, there may be even more patients with this chromosomal abnormality, but they probably die before being diagnosed due to unfavorable socioeconomic conditions. This could explain the low prevalence of this chromosomal abnormality observed in the present study.

  13. Pyrrolidine dithiocarbamate reduces the progression of total kidney volume and cyst enlargement in experimental polycystic kidney disease

    OpenAIRE

    Ta, Michelle H. T.; Rao, Padmashree; Korgaonkar, Mayuresh; Foster, Sheryl F.; Peduto, Anthony; Harris, David C. H.; Rangan, Gopala K

    2014-01-01

    Abstract Heterocyclic dithiocarbamates have anti‐inflammatory and anti‐proliferative effects in rodent models of chronic kidney disease. In this study, we tested the hypothesis that pyrrolidine dithiocarbamate (PDTC) reduces the progression of polycystic kidney disease (PKD). Male Lewis polycystic kidney (LPK) rats (an ortholog of Nek8/NPHP9) received intraperitoneal injections of either saline vehicle or PDTC (40 mg/kg once or twice daily) from postnatal weeks 4 until 11. By serial magnetic ...

  14. Redefining disease through advances in nuclear medicine

    International Nuclear Information System (INIS)

    Full text: Nuclear Imaging has progressed significantly in the last decade. The disease is being explored at receptor antigenic and biochemical level. The Molecular Imaging with tracers such as the 18-Fluro-Deoxy-Glucose (FDG), 11C-thymidine, 18-Fluro-Estradiol have enabled us to look into different aspects of disease. The FDG helps us in understanding aggressiveness of tumor and thereby survival of a cancer patient. It is enabling us to redefine disease at metabolic level leading to 'Metabolic Classification' of disease. The 18-Fluro-Estradiol scan is exploring breast cancer at receptor level and has enabled us to understand why some breast cancer patients do not respond to the hormone therapy. The 11C-Thymidine scan is able to image proliferative capacity of a tumor and thereby impact on the treatment approach. In addition to the field on oncology, recent advances in Nuclear Imaging are now providing valuable insights in understanding of various other human diseases. We are now redefining Alzheimer's disease and some of the psychiatric illnesses like Schizophrenia and Depression through the new Nuclear Imaging techniques. The years ahead will see extensive application of Nuclear Imaging technology in human disorders. Metabolic Classification of disease would bring out the processes underlying the causation and manifestation of diverse human disorders and help redefine the disease with the aim of more effective and less toxic personalized medicine

  15. Fibrocystic disease of the breast: Analysis of sonographic findings with histopathologic correlation

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Kyoung Suk; Kim, Chung Hyun; Lee, Chung Keun; Oh, Young Ran; Cho, June Sik; Rhee, Byung Chull; Kang, Dong Wook [Chungnam National University College of Medicine, Daejeon (Korea, Republic of)

    1994-12-15

    To evaluate the sonographic findings of fibrocystic disease with histopathologic correlation, we retrospectively analyzed the sonographic findings and pathologic findings of 48 cases with histopathologically proven fibrocystic disease. The sonographic pattern of the lesions were classified into type I (ill define disoechoic lesion), Type IIa (ill defined hypoechoic lesion with heterogeneity), Type IIb (ill defined hypoechoiclesion with nodularities), Type III (mass lesion with thick or thin boundary echoes). The pathologic feature was classified into stromal hyperplasia, mixed, proliferative and fibroadenomatosis patterns. In sonographic type I,stromal hyperplasia and mixed patterns were seen in 77% and 23% , respectively. In sonographic Type IIa, stromal hyperplasia, mixed and proliferative patterns were seen in 57%, 29% and 14%, respectively. In sonographic TypeIIb, stromal hyperplasia and mixed patterns were seen in 17% and 83%, respectively. In sonographic type III, stromal hyperplasia, mixed, proliferative and fire-and-brimstone patterns were seen in 10%, 23%,13% and 54%, respectively.In conclusion, the sonographic findings of fibrocystic disease were variable and were not correlated good with histopathologic patterns. Sonography might to be helpful in the diagnosis of fibrocystic disease in conjunction with other imaging modalities in cases with Type I or Type II sonographic patterns. However, in cases with Type III patterns, biopsy should be performed to differentiate them from other benign or malignant masses

  16. Searching in mother nature for anti-cancer activity: anti-proliferative and pro-apoptotic effect elicited by green barley on leukemia/lymphoma cells.

    Directory of Open Access Journals (Sweden)

    Elisa Robles-Escajeda

    Full Text Available Green barley extract (GB was investigated for possible anti-cancer activity by examining its anti-proliferative and pro-apoptotic properties on human leukemia/lymphoma cell lines. Our results indicate that GB exhibits selective anti-proliferative activity on a panel of leukemia/lymphoma cells in comparison to non-cancerous cells. Specifically, GB disrupted the cell-cycle progression within BJAB cells, as manifested by G2/M phase arrest and DNA fragmentation, and induced apoptosis, as evidenced by phosphatidylserine (PS translocation to the outer cytoplasmic membrane in two B-lineage leukemia/lymphoma cell lines. The pro-apoptotic effect of GB was found to be independent of mitochondrial depolarization, thus implicating extrinsic cell death pathways to exert its cytotoxicity. Indeed, GB elicited an increase of TNF-α production, caspase-8 and caspase-3 activation, and PARP-1 cleavage within pre-B acute lymphoblastic leukemia Nalm-6 cells. Moreover, caspase-8 and caspase-3 activation and PARP-1 cleavage were strongly inhibited/blocked by the addition of the specific caspase inhibitors Z-VAD-FMK and Ac-DEVD-CHO. Furthermore, intracellular signaling analyses determined that GB treatment enhanced constitutive activation of Lck and Src tyrosine kinases in Nalm-6 cells. Taken together, these findings indicate that GB induced preferential anti-proliferative and pro-apoptotic signals within B-lineage leukemia/lymphoma cells, as determined by the following biochemical hallmarks of apoptosis: PS externalization, enhanced release of TNF-α, caspase-8 and caspase-3 activation, PARP-1 cleavage and DNA fragmentation Our observations reveal that GB has potential as an anti-leukemia/lymphoma agent alone or in combination with standard cancer therapies and thus warrants further evaluation in vivo to support these findings.

  17. 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

  18. 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.

  19. Evaluation of estrogen receptor alpha and beta and progesterone receptor expression and correlation with clinicopathologic factors and proliferative marker Ki-67 in breast cancers

    DEFF Research Database (Denmark)

    Rosa, Fabíola E; Caldeira, José R F; Felipes, Joice;

    2008-01-01

    in 68%, 78%, and 49% of the cases, respectively. Tumor grade was negatively correlated with transcript and protein levels of ER-alpha (P = .0169 and P = .0006, respectively) and PGR (P = .0034 and P = .0005, respectively). Similarly, proliferative index Ki-67 was negatively associated with transcript...... statistical difference was observed between lymph node status and ER-beta protein expression (P = .0208). In ER-alpha-negative tumors, we detected a correlation between ER-beta protein expression and high levels of Ki-67. These data suggest that ER-beta could be a prognostic marker in human breast cancer....

  20. Aplysinopsin Analogs: Synthesis and Anti-proliferative Activity of Substituted (Z)-5-(N-benzylindol-3-ylmethylene)imidazolidine-2,4-diones

    OpenAIRE

    Reddy, Y. Thirupathi; Reddy, P. Narsimha; Koduru, Srinivas; Damodaran, Chendil; Crooks, Peter A.

    2010-01-01

    A series of substituted (Z)-5-(N-benzylindol-3-ylmethylene)imidazolidine-2,4-dione (3) analogs structurally related to aplysinopsin, and that incorporate a variety of substituents in both the indole and N-benzyl moieties have been synthesized under microwave irradiation and conventional heating methods These analogs were evaluated for their anti-proliferative activity against MCF-7 and MDA-231 breast cancer cell lines, and A549 and H460 lung cancer cell lines. Two analogs, 3f and 3j had IC50 ...

  1. 1-calcium phosphate-uracil, a synthesized pyrimidine derivative agent, has anti-proliferative, pro-apoptotic and anti-invasion effects on multiple tumor cell lines

    OpenAIRE

    Peng, Jing; Chen, Xinlian; Hu, Qian; Yang, Mei; Liu, Hongqian; Wei, Wei; Liu, Shanling; Wang, HE

    2014-01-01

    1-calcium phosphate-uracil (1-CP-U), a synthetic pyrimidine derivative, has been documented to demonstrate a variety of different biological activities. However, the potency and mechanisms of this agent’s anti-cancer activity have not been elucidated to date. In the present study, the anti-cancer effects of 1-CP-U were examined in a range of in vitro assays. Different cell lines were treated with 1-CP-U at varied concentrations (0.7, 1.0, 1.4 μmol/l) for indicated durations. The cell prolifer...

  2. 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

    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...... antibody (MIB-1), which is applicable on formalin-fixed, paraffin-embedded tissue after microwave pretreatment. OA-519 was expressed in about one-third of the tumours and the percentage of proliferating cells (the MIB-1 index) ranged between 1 and 72 per cent (median 17 per cent). Using multivariate Cox...

  3. Homeodomain protein DLX4 counteracts key transcriptional control mechanisms of the TGF-β cytostatic program and blocks the anti-proliferative effect of TGF-β

    OpenAIRE

    Trinh, Bon Quy; Barengo, Nicolas; Naora, Honami

    2011-01-01

    The anti-proliferative activity of transforming growth factor-β (TGF-β) is essential for maintaining normal tissue homeostasis and is lost in many types of tumors. Gene responses that are central to the TGF-β cytostatic program include activation of the cyclin-dependent kinase inhibitors p15Ink4B and p21WAF1/Cip1 and repression of c-myc. These gene responses are tightly regulated by a repertoire of transcription factors that include Smad proteins and Sp1. The DLX4 homeobox patterning gene enc...

  4. Glomerular Diseases

    Science.gov (United States)

    ... Research Training & Career Development Grant programs for students, postdocs, and faculty Research at NIDDK Labs, faculty, and ... diabetes, digestive and liver diseases, kidney diseases, weight control and nutrition, urologic diseases, endocrine and metabolic diseases, ...

  5. Kawasaki Disease

    Science.gov (United States)

    ... Content Article Body What is Kawasaki disease? Kawasaki disease is a serious and perplexing disease, the cause of which is ... influenza) with aspirin has been linked with a serious disease called Reye syndrome. Always consult your pediatrician before ...

  6. Diseases of the respiratory tract of chelonians.

    Science.gov (United States)

    Origgi, F C; Jacobson, E R

    2000-05-01

    Diseases of the respiratory tract commonly occur in captive chelonians, and several diseases also have occurred in wild chelonians. Infectious causes include viruses, bacteria, fungi, and parasites. Herpesviruses have surfaced as important pathogens of the oral cavity and respiratory tract in Hermann's tortoise (Testudo hermanii), spur-thighed tortoise (Testudo graeca), and other tortoises in Europe and the United States. Herpesvirus-associated respiratory diseases also have been reported in the green turtle, Chelonia mydas, in mariculture in the Cayman Islands. Of diseases caused by bacteria, an upper respiratory tract disease caused by Mycoplasma sp has been reported in free-hanging and captive gopher tortoises in the southeastern United States and in desert tortoises in the Mojave Desert of the southwestern United States. Mycotic pulmonary disease is commonly reported in captive chelonians, especially in those maintained at suboptimal temperatures. An intranuclear coccidia has been seen in several species of captive tortoises in the United States, and, in one case, a severe proliferative pneumonia was associated with organisms in the lung. The most common noninfectious cause of respiratory disease in chelonians results from trauma to the carapace. Although pulmonary fibromas commonly occur in green turtles with fibropapillomatosis, for the most part, tumors of the respiratory tract are uncommon in chelonians. PMID:11228895

  7. Ribbing disease

    International Nuclear Information System (INIS)

    Ribbing disease is a rare sclerosing dysplasia that involves long tubular bones, especially the tibia and femur. It occurs after puberty and is reported to be more common in women. In this article we describe how Ribbing disease can be differentiated from diseases like Engelmann-Camurati disease, van Buchem disease, Erdheim-Chester disease, osteoid osteoma, chronic osteomyelitis, stress fracture, etc

  8. Ganglioside-Dependent Neural Stem Cell Proliferation in Alzheimer’s Disease Model Mice

    OpenAIRE

    Koon, Noah A.; Itokazu, Yutaka; Yu, Robert K.

    2015-01-01

    The aggregation and formation of amyloid plaques by amyloid β-peptides (Aβs) is believed to be one of the pathological hallmarks of Alzheimer’s disease (AD). Intriguingly, Aβs have also been shown to possess proliferative effects on neural stem cells (NSCs). Many essential cellular processes in NSCs, such as fate determination and proliferation, are heavily influenced by cell surface glycoconjugates, including gangliosides. It has recently been shown that Aβ1-42 alters several key glycosyltra...

  9. Idiopathic CD4+ T lymphopenia without autoimmunity or granulomatous disease in the slipstream of RAG mutations

    OpenAIRE

    Kuijpers, Taco W.; IJspeert, Hanna; Leeuwen, Ester; Jansen, Machiel H.; Mette D Hazenberg; Weijer, Kees; Van Lier, Rene A. W.; van der Burg, Mirjam

    2011-01-01

    textabstractA girl presented during childhood with a single course of extensive chickenpox and moderate albeit recurrent pneumonia in the presence of idiopathic CD4+T lymphocytopenia (ICL). Her clinical condition remained stable over the past 10 years without infections, any granulomatous disease, or autoimmunity. Immunophenotyping demonstrated strongly reduced naive T and B cells with intact proliferative capacity. Antibody reactivity on in vivo immunizations was normal. T-cell receptor-Vβ r...

  10. 25-Gauge Microincision Vitrectomy to Treat Vitreoretinal Disease in Glaucomatous Eyes after Trabeculectomy

    OpenAIRE

    Hiroshi Kunikata; Naoko Aizawa; Nobuo Fuse; Toshiaki Abe; Toru Nakazawa

    2014-01-01

    Purpose. To determine the feasibility of using 25-gauge microincision vitrectomy surgery (25GMIVS) to treat vitreoretinal disease in glaucomatous eyes which have previously undergone trabeculectomy (TLE). Methods. A consecutive, interventional case series. We performed 25GMIVS in 15 glaucomatous eyes that had undergone TLE. Follow-up period was 11.5 months. Results. 25GMIVS was successfully used and led to improvement in visual acuity (P < 0.01). We performed 25GMIVS for proliferative diabeti...

  11. Intraglomerular deposition of fibrin/fibrinogen-related antigen in children with various renal diseases.

    OpenAIRE

    Kamitsuji, H.; Sakamoto, S.; Matsunaga, T; Taira, K; Kawahara, S.; Nakajima, M.

    1988-01-01

    The localization of intraglomerular deposits of fibrin (Fb)/fibrinogen (Fg)-related antigen (FRA) in children with various glomerular diseases was determined by an immunohistopathologic method using an anti-Fg antibody capable of detecting FRA, an anti-D-dimer antibody capable of detecting crosslinked Fb (XLFb) and its derivatives (XLFbDP), and by a method using the effect of monochloroacetic acid (MCA) treatment on kidney sections. In proliferative glomerulonephritis (PGN), XLFbs were detect...

  12. mTOR and vascular remodeling in lung diseases: current challenges and therapeutic prospects

    OpenAIRE

    Goncharova, Elena A

    2013-01-01

    Mammalian target of rapamycin (mTOR) is a major regulator of cellular metabolism, proliferation, and survival that is implicated in various proliferative and metabolic diseases, including obesity, type 2 diabetes, hamartoma syndromes, and cancer. Emerging evidence suggests a potential critical role of mTOR signaling in pulmonary vascular remodeling. Remodeling of small pulmonary arteries due to increased proliferation, resistance to apoptosis, and altered metabolism of cells forming the pulmo...

  13. Modern immunomorphological aspects of diagnostics of periodontal diseases

    Directory of Open Access Journals (Sweden)

    Ostrovskaya L.U.

    2013-09-01

    Full Text Available Molecular markers of destruction of periodontal tissue and alveolar bone belong to the mediators, participating in maintenance of chronic inflammatory process in the clinical attachment. Purpose: To reveal changes of cytokine profile of gingival fluid and proliferative activity of cells of gum at patients with inflammatory periodontal diseases. Material and methods. Immunohistochemical research of biopsy gum material of 70 patients with periodontal disease with monoclonal antibodies: Ki-67 (marker of proliferative activity of cells, Bcl-2 (apoptosis marker; method of the solid-phase immunofermental analysis for level definition interleukin -6, 10, 12, 18 in gingival fluid (about — and anti-inflammatory markers. Results. It is shown that level definition of cytokines in gingival fluid allows to monitor the activity of the inflammatory process in the periodontal tissues, and the morphometric analysis of periodontal cells reflects degree of its weight. Conclusion. The use of molecular markers in inspection of patients with periodontal disease is the informative method, allowing to predict development and course of chronic periodontal disease.

  14. Low-dose radiation pretreatment improves survival of human ceiling culture-derived proliferative adipocytes (ccdPAs) under hypoxia via HIF-1 alpha and MMP-2 induction

    Energy Technology Data Exchange (ETDEWEB)

    Adachi, Naoki [Department of Plastic Surgery, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba-city, Chiba, #260-8677 (Japan); Kubota, Yoshitaka, E-mail: kubota-cbu@umin.ac.jp [Department of Plastic Surgery, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba-city, Chiba, #260-8677 (Japan); Kosaka, Kentarou; Akita, Shinsuke; Sasahara, Yoshitarou; Kira, Tomoe [Department of Plastic Surgery, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba-city, Chiba, #260-8677 (Japan); Kuroda, Masayuki [Center for Advanced Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba-city, Chiba, #260-8677 (Japan); Mitsukawa, Nobuyuki [Department of Plastic Surgery, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba-city, Chiba, #260-8677 (Japan); Bujo, Hideaki [Department of Clinical-Laboratory and Experimental-Research Medicine, Toho University, Sakura Medical Center, 564-1 Shimoshizu, Sakura-shi, Chiba, #285-8741 (Japan); Satoh, Kaneshige [Department of Plastic Surgery, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba-city, Chiba, #260-8677 (Japan)

    2015-08-07

    Poor survival is a major problem of adipocyte transplantation. We previously reported that VEGF and MMPs secreted from transplanted adipocytes are essential for angiogenesis and adipogenesis. Pretreatment with low-dose (5 Gy) radiation (LDR) increased VEGF, MMP-2, and HIF-1 alpha mRNA expression in human ceiling culture-derived proliferative adipocytes (hccdPAs). Gene expression after LDR differed between adipose-derived stem cells (hASCs) and hccdPAs. Pretreatment with LDR improved the survival of hccdPAs under hypoxia, which is inevitable in the early stages after transplantation. Upregulation of VEGF and MMP-2 after LDR in hccdPAs is mediated by HIF-1 alpha expression. Our results suggest that pretreatment with LDR may improve adipocyte graft survival in a clinical setting through upregulation of VEGF and MMP-2 via HIF-1 alpha. - Highlights: • Ceiling culture-derived proliferative adipocytes (ccdPAs) react to radiation. • Low-dose radiation (LDR) pretreatment improves survival of ccdPAs under hypoxia. • Gene expression after LDR differs between ccdPAs and adipose-derived stem cells. • LDR-induced increase in MMP-2 and VEGF is dependent on HIF-1 alpha induction. • LDR pretreatment may improve the adipocyte graft survival rate in clinical settings.

  15. The G protein-coupled receptor GPR30 mediates the proliferative and invasive effects induced by hydroxytamoxifen in endometrial cancer cells

    International Nuclear Information System (INIS)

    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.

  16. The Adipocyte-Derived Hormone Leptin Has Proliferative Actions on Androgen-Resistant Prostate Cancer Cells Linking Obesity to Advanced Stages of Prostate Cancer

    Directory of Open Access Journals (Sweden)

    M. Raschid Hoda

    2012-01-01

    Full Text Available Background. Because obesity may be a risk factor for prostate cancer, we investigated proliferative effects of adipocytes-derived hormone leptin on human prostate cancer cells and assessed the role of mitogen-activated protein kinase (MAPK signaling pathway in mediating these actions. Material and Methods. Three human prostate cancer cell lines were treated with increasing doses of recombinant leptin. Cell growth was measured under serum-free conditions using a spectrophotometric assay. Further, Western blotting was applied to detect the phosphorylation of an ERK1/2, and a specific inhibitor of MAPK (PD98059; 40 μM was used. Results. In both androgen-resistant cell lines DU145 and PC-3, cell growth was dose-dependently increased by leptin after 24 hrs and 48 hrs of incubation, whereas leptin’s proliferative effects on androgen-sensitive cell line LNCaP was less pronounced. Further, leptin caused dose-dependent ERK1/2 phosphorylation in both androgen-resistant cell lines, and pretreatment of these cells with PD98059 inhibited these responses. Conclusions. Leptin may be a potential link between obesity and risk of progression of prostate cancer. Thus, studies on leptin and obesity association to prostate cancer should differentiate patients according to androgen sensitivity.

  17. A case-control study of oral epithelial proliferative markers among Sudanese Toombak dippers using micronuclei assay, argyrophilic nucleolar organizer region, Papanicolaou and crystal violet methods

    Directory of Open Access Journals (Sweden)

    Anass M. Abbas

    2013-07-01

    Full Text Available The use of Toombak has been reported to play a major role in the etiology of oral cancer in Sudan. The cellular proliferative activity on the oral epithelium of 210 Toombak dippers was assessed by applying the micronuclei frequency, mean argyrophilic nucleolar organizer region (AgNOR counts, Papanicolaou method, and 1% crystal violet stain. Participants were divided into 3 groups: 200 were apparently healthy individuals, 100 were Toombak users (cases, 100 were non-tobacco users (control and 10 were patients with oral squamous cell carcinomas. Cytological atypia was identified among 4 (4%. Toombak users and was not found among the control group (P<0.04. The micronuclei frequencies were higher in Toombak users (1.026 than in the control group (0.356 (P<0.0001. The mean AgNOR counts in Toombak users (2.423 were higher than control group (1.303 (P<0.0001. Neither Toombak users nor control group showed mitotic figures in 1% crystal violet method. The results of this research showed that Toombak dipping is a high risk factor for increase in the cellular proliferation in the oral mucosa. The cytological proliferative marker methods used are useful for screening Toombak users.

  18. Phlorizin, an Active Ingredient of Eleutherococcus senticosus, Increases Proliferative Potential of Keratinocytes with Inhibition of MiR135b and Increased Expression of Type IV Collagen.

    Science.gov (United States)

    Choi, Hye-Ryung; Nam, Kyung-Mi; Lee, Hyun-Sun; Yang, Seung-Hye; Kim, Young-Soo; Lee, Jongsung; Date, Akira; Toyama, Kazumi; Park, Kyoung-Chan

    2016-01-01

    E. senticosus extract (ESE), known as antioxidant, has diverse pharmacologic effects. It is also used as an antiaging agent for the skin and phlorizin (PZ) is identified as a main ingredient. In this study, the effects of PZ on epidermal stem cells were investigated. Cultured normal human keratinocytes and skin equivalents are used to test whether PZ affects proliferative potential of keratinocytes and how it regulates these effects. Skin equivalents (SEs) were treated with ESE and the results showed that the epidermis became slightly thickened on addition of 0.002% ESE. The staining intensity of p63 as well as proliferating cell nuclear antigen (PCNA) is increased, and integrin α6 was upregulated. Analysis of ESE confirmed that PZ is the main ingredient. When SEs were treated with PZ, similar findings were observed. In particular, the expression of integrin α6, integrin β1, and type IV collagen was increased. Levels of mRNA for type IV collagen were increased and levels of miR135b were downregulated. All these findings suggested that PZ can affect the proliferative potential of epidermal cells in part by microenvironment changes via miR135b downregulation and following increased expression of type IV collagen. PMID:27042261

  19. Phlorizin, an Active Ingredient of Eleutherococcus senticosus, Increases Proliferative Potential of Keratinocytes with Inhibition of MiR135b and Increased Expression of Type IV Collagen

    Directory of Open Access Journals (Sweden)

    Hye-Ryung Choi

    2016-01-01

    Full Text Available E. senticosus extract (ESE, known as antioxidant, has diverse pharmacologic effects. It is also used as an antiaging agent for the skin and phlorizin (PZ is identified as a main ingredient. In this study, the effects of PZ on epidermal stem cells were investigated. Cultured normal human keratinocytes and skin equivalents are used to test whether PZ affects proliferative potential of keratinocytes and how it regulates these effects. Skin equivalents (SEs were treated with ESE and the results showed that the epidermis became slightly thickened on addition of 0.002% ESE. The staining intensity of p63 as well as proliferating cell nuclear antigen (PCNA is increased, and integrin α6 was upregulated. Analysis of ESE confirmed that PZ is the main ingredient. When SEs were treated with PZ, similar findings were observed. In particular, the expression of integrin α6, integrin β1, and type IV collagen was increased. Levels of mRNA for type IV collagen were increased and levels of miR135b were downregulated. All these findings suggested that PZ can affect the proliferative potential of epidermal cells in part by microenvironment changes via miR135b downregulation and following increased expression of type IV collagen.

  20. Low-dose radiation pretreatment improves survival of human ceiling culture-derived proliferative adipocytes (ccdPAs) under hypoxia via HIF-1 alpha and MMP-2 induction

    International Nuclear Information System (INIS)

    Poor survival is a major problem of adipocyte transplantation. We previously reported that VEGF and MMPs secreted from transplanted adipocytes are essential for angiogenesis and adipogenesis. Pretreatment with low-dose (5 Gy) radiation (LDR) increased VEGF, MMP-2, and HIF-1 alpha mRNA expression in human ceiling culture-derived proliferative adipocytes (hccdPAs). Gene expression after LDR differed between adipose-derived stem cells (hASCs) and hccdPAs. Pretreatment with LDR improved the survival of hccdPAs under hypoxia, which is inevitable in the early stages after transplantation. Upregulation of VEGF and MMP-2 after LDR in hccdPAs is mediated by HIF-1 alpha expression. Our results suggest that pretreatment with LDR may improve adipocyte graft survival in a clinical setting through upregulation of VEGF and MMP-2 via HIF-1 alpha. - Highlights: • Ceiling culture-derived proliferative adipocytes (ccdPAs) react to radiation. • Low-dose radiation (LDR) pretreatment improves survival of ccdPAs under hypoxia. • Gene expression after LDR differs between ccdPAs and adipose-derived stem cells. • LDR-induced increase in MMP-2 and VEGF is dependent on HIF-1 alpha induction. • LDR pretreatment may improve the adipocyte graft survival rate in clinical settings

  1. 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.

  2. Short-term pathological and proliferative effects of butylated hydroxy anisole and other phenolic antioxidants in the forestomach of Fischer 344 rats

    International Nuclear Information System (INIS)

    Food grade butylated hydroxyanisole (BHA) when incorporated in the diet and fed to male Fischer 344 rats for 9 or 27 days induced proliferative squamous epithelial changes in the lesser curvature of the forestomach proximate to the plandular stomach. These changes were assessed histopathologically and by (methyl-3H) thymidine radioautography. It was shown that BHA mixed dry into powdered diet, incorporated into the diet in corn oil, or in a pelleted diet, induced similar effects. When levels of 2%, 1%, 0.5%, 0.25%, 0.1% and BHA were incorporated in rat diet for 9 days, the proliferative effect appeared to show a no effect level at 0.25% based on the (methyl-3H) thymidine-labelling index. Other food use antioxidants, namely butylated hydroxytoluene or tertiary butylhydroquinone, induced a lesser reponse than BHA at the maximum dose employed in the study. Propyl gallate was without effect. Propyl-4-hydroxybenzoate, a food use phenol, on the other hand, induced a less pronounced response that BHA but was more effective than the other antioxidants. Because increased cellular proliferation often provides an optimal milieu for tumor formation, it is suggested that these observations may be relevant to rat forestomach tumors induced by BHA (author)

  3. Herpes simplex virus (HSV)-specific proliferative and cytotoxic T-cell responses in humans immunized with an HSF type 2 glycoprotein subunit vaccine

    International Nuclear Information System (INIS)

    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

  4. Enhanced proliferative cellular responses to HIV-1 V3 peptide and gp120 following immunization with V3:Ty virus-like particles.

    Science.gov (United States)

    Harris, S J; Gearing, A J; Layton, G T; Adams, S E; Kingsman, A J

    1992-11-01

    The induction of CD4+ T-helper (Th) cell responses is likely to be an important requirement of vaccine candidates designed to prevent or moderate human immunodeficiency virus-1 (HIV-1) infection. We have investigated the ability of hybrid Ty virus-like particles carrying the V3 loop region of the HIV-1 IIIB envelope gp120 (V3:Ty-VLP) to elicit V3-specific proliferative responses. Significant proliferation in response to stimulation in vitro with homologous IIIB V3 peptide was observed following immunization of mice with V3:Ty-VLP either as an aluminium hydroxide precipitate or without adjuvant. Responses to MN V3 peptide were also observed in certain mouse haplotypes. To assess the effect of presenting the V3 loop in this particulate form, we compared the responses induced by V3:Ty-VLP with those obtained with two non-particulate immunogens, recombinant gp120 (rgp120) and V3 peptide conjugated to albumin. V3-specific responses to V3 peptide in vitro were reproducibly higher following immunization with V3:Ty-VLP than with either rgp120 or V3-albumin coagulate (V3-alb). The data indicate that immunization with the V3 loop as a hybrid Ty-VLP results in enhanced proliferative responses to V3 peptide and recognition of rgp120 in vitro. Some cross-reactivity of Th cells for V3 sequences from different isolates was also observed. PMID:1362183

  5. 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.

  6. 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.

  7. New steroidal 17β-carboxy derivatives present anti-5α-reductase activity and anti-proliferative effects in a human androgen-responsive prostate cancer cell line.

    Science.gov (United States)

    Amaral, Cristina; Varela, Carla; Correia-da-Silva, Georgina; Tavares da Silva, Elisiário; Carvalho, Rui A; Costa, Saul C P; Cunha, Sara C; Fernandes, José O; Teixeira, Natércia; Roleira, Fernanda M F

    2013-11-01

    The androgens testosterone (T) and dihydrotestosterone (DHT), besides playing an important role in prostate development and growth, are also responsible for the development and progression of benign prostate hyperplasia (BPH) and prostate cancer. Therefore, the actions of these hormones can be antagonized by preventing the irreversible conversion of T into DHT by inhibiting 5α-reductase (5α-R). This has been a useful therapeutic approach for the referred diseases and can be achieved by using 5α-reductase inhibitors (RIs). Steroidal RIs, finasteride and dutasteride, are used in clinic for BPH treatment and were also proposed for chemoprevention of prostate cancer. Nevertheless, due to the increase in bone and muscle loss, impotency and occurrence of high-grade prostate tumours, it is important to seek for other potent and specific molecules with lower side effects. In the present work, we designed and synthesized steroids with the 3-keto-Δ(4) moiety in the A-ring, as in the 5α-R substrate T, and with carboxamide, carboxyester or carboxylic acid functions at the C-17β position. The inhibitory 5α-R activity, in human prostate microsomes, as well as the anti-proliferative effects of the most potent compounds, in a human androgen-responsive prostate cancer cell line (LNCaP cells), were investigated. Our results showed that steroids 3, 4 and 5 are good RIs, which suggest that C-17β lipophylic amides favour 5α-R inhibition. Moreover, these steroids induce a decrease in cell viability of stimulated LNCaP cells, in a 5α-R dependent-manner, similarly to finasteride. PMID:23933094

  8. Renal involvement in behcet's disease

    International Nuclear Information System (INIS)

    There are conflicting reports about the renal involvement in Behcet's disease (BD). In this study we aimed to study the frequency and type of renal involvement in a group of patients with BD in Azerbaijan province that is one of the prevalent areas of BD in Iran. All cases of BD were prospectively followed between June 2004 and January 2007, and evaluated for renal dys-function (serum creatinine > 1.7 mg/dL), glomerular hematuria and proteinuria. Those patients with proteinuria > 500 mg/day and serum creatinine level > 2 mg/dL, underwent renal biopsy. From a total number of 100 patients, six patients (6%) had obvious renal involvements. Four patients had glomerular hematuria and proteinuria. Renal biopsy in two of them revealed measangial proliferative glumerulonephritis with IgA deposit in one of them and membranoproliferative glumerolonephritis in another one. Two remaining patients had serum creatinine > 2 mg/dL without any hematuria or proteinuria. Serologic study for viral agents and collagen vascular disease were negative in all patients with renal involvements. In conclusion, renal involvement in BD is not infrequent, although in most cases it is mild in nature and may be missed. (author)

  9. Activation of the MEK5/ERK5 Cascade Is Responsible for Biliary Dysgenesis in a Rat Model of Caroli’s Disease

    OpenAIRE

    Sato, Yasunori; Harada, Kenichi; Kizawa, Kazuo; Sanzen, Takahiro; Furubo, Shinichi; Yasoshima, Mitsue; Ozaki, Satoru; Ishibashi, Masahiko; Nakanuma, Yasuni

    2005-01-01

    Polycystic kidney (PCK) rats exhibit a multiorgan cyst pathology similar to human autosomal recessive polycystic kidney disease, and are proposed as an animal model of Caroli’s disease with congenital hepatic fibrosis (CHF). This study investigated the expression and function of selected components of the mitogen activated protein kinase (MAPK) pathway in cultured intrahepatic biliary epithelial cells (BECs) of PCK rats. Compared to the proliferative activity of cultured BECs of control rats,...

  10. Estrogens and autoimmune diseases.

    Science.gov (United States)

    Cutolo, Maurizio; Capellino, Silvia; Sulli, Alberto; Serioli, Bruno; Secchi, Maria Elena; Villaggio, Barbara; Straub, Rainer H

    2006-11-01

    Sex hormones are implicated in the immune response, with estrogens as enhancers at least of the humoral immunity and androgens and progesterone (and glucocorticoids) as natural immune-suppressors . Several physiological, pathological, and therapeutic conditions may change the serum estrogen milieu and/or peripheral conversion rate, including the menstrual cycle, pregnancy, postpartum period, menopause, being elderly, chronic stress, altered circadian rhythms, inflammatory cytokines, and use of corticosteroids, oral contraceptives, and steroid hormonal replacements, inducing altered androgen/estrogen ratios and related effects. In particular, cortisol and melatonin circadian rhythms are altered, at least in rheumatoid arthritis (RA), and partially involve sex hormone circadian synthesis and levels as well. Abnormal regulation of aromatase activity (i.e., increased activity) by inflammatory cytokine production (i.e., TNF-alpha, IL-1, and IL-6) may partially explain the abnormalities of peripheral estrogen synthesis in RA (i.e., increased availability of 17-beta estradiol and possible metabolites in synovial fluids) and in systemic lupus erythematosus, as well as the altered serum sex-hormone levels and ratio (i.e., decreased androgens and DHEAS). In the synovial fluids of RA patients, the increased estrogen concentration is observed in both sexes and is more specifically characterized by the hydroxylated forms, in particular 16alpha-hydroxyestrone, which is a mitogenic and cell proliferative endogenous hormone. Local effects of sex hormones in autoimmune rheumatic diseases seems to consist mainly in modulation of cell proliferation and cytokine production (i.e., TNF-alpha, Il-1, IL-12). In this respect, it is interesting that male patients with RA seem to profit more from anti-TNFalpha strategies than do female patients. PMID:17261796

  11. Alzheimer's Disease

    Science.gov (United States)

    Alzheimer's disease (AD) is the most common form of dementia among older people. Dementia is a brain disorder that ... higher if a family member has had the disease. No treatment can stop the disease. However, some ...

  12. Infectious Diseases

    Science.gov (United States)

    Infectious diseases kill more people worldwide than any other single cause. Infectious diseases are caused by germs. Germs are tiny living ... to live NIH: National Institute of Allergy and Infectious Diseases

  13. Heart Disease

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    ... Got Homework? Here's Help White House Lunch Recipes Heart Disease KidsHealth > For Kids > Heart Disease Print A A ... chest pain, heart attacks, and strokes . What Is Heart Disease? The heart is the center of the cardiovascular ...

  14. Lyme disease

    Science.gov (United States)

    ... Causes Lyme disease is caused by bacteria called Borrelia burgdorferi ( B burgdorferi ). Blacklegged ticks and other species of ... Names Borreliosis; Bannwarth syndrome Images Lyme disease organism, Borrelia burgdorferi Tick, deer engorged on the skin Lyme disease - ...

  15. Huntington's Disease

    Science.gov (United States)

    Huntington's disease (HD) is an inherited disease that causes certain nerve cells in the brain to waste ... express emotions. If one of your parents has Huntington's disease, you have a 50 percent chance of ...

  16. Krabbe disease

    Science.gov (United States)

    ... for Krabbe disease. Some people have had a bone marrow transplant in the early stages of the disease, but ... counseling is recommended for people with a family history of Krabbe disease who are considering having children. ...

  17. Stargardt Disease

    Science.gov (United States)

    ... Congenital Amaurosis Macular Degeneration Retinitis Pigmentosa Stargardt Disease Usher Syndrome Other Retinal Diseases Glossary News & Research News & ... for retinal degenerative diseases like retinitis pigmentosa (RP), Usher syndrome and macular degeneration . Back to top What ...

  18. Reportable diseases

    Science.gov (United States)

    Notifiable diseases ... Centers for Disease Control and Prevention. National Notifiable Diseases Surveillance System (NNDSS). Last updated May 4, 2015. Available at: wwwn.cdc.gov/nndss . Accessed September 9, 2015.

  19. Crohn's Disease

    Science.gov (United States)

    Crohn's disease causes inflammation of the digestive system. It is one of a group of diseases called inflammatory ... small intestine called the ileum. The cause of Crohn's disease is unknown. It may be due to an ...

  20. Wilson Disease

    Science.gov (United States)

    ... Wilson disease. Health care providers do not use brain imaging tests to diagnose Wilson disease, though certain findings ... testing. [ Top ] Clinical Trials The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and other ...