A new species of Bathymedon Sars, 1892 (Amphipoda: Oedicerotidae from the western Mediterranean bathyal floor

Directory of Open Access Journals (Sweden)

Damiá Jaume

1998-12-01

Full Text Available Bathymedon longirostris sp. nov. (Amphipoda: Oedicerotidae from the western Mediterranean bathyal suprabenthos is described. It is characterised by the well-developed rostrum; the discrete lateral lobe of head; the elongation of the peduncle segment 3 of the first antenna; the very slender propodus of the second gnathopod, which attains maximum width not at the palm angle, but at about midway along the palm margin; and by the relative length of the carpus of the foregoing limb, sub-equal to propodus. The discovery of a tiny remnant of the 2nd peduncle segment of the first antenna in the new species is commented with regard to the homologation of the peduncle segments in other members of the Family. The new taxon was captured below 593 m over muddy bottoms with pteropod shells and remains of planktonic foraminiferans. It was one of the most common amphipods in the lower slope (below ~ 1000 m, whereas in the depth range comprised between 1250 and 1859 m it was the second dominant species, representing 11.4 % of the total gammarideans captured. The area studied harbours three additional congeneric species, although their populations are mainly concentrated in the upper and middle slope. Over the bottom, adult males of the new species apparently tend to occupy higher levels beyond the water-sediment interface than the rest of demographic categories. The gut content of three individuals revealed a bulk of calcified foraminiferans, a diet in consonance with their massive mandibles. Juvenile individuals were more abundant in winter, whereas adult individuals were clearly dominant in summer, thus suggesting the biological cycle of the species follows some type of periodicity.

Effectiveness of oxfendazole against early and later 4th-stage Strongylus vulgaris in ponies.

Science.gov (United States)

Slocombe, J O; McCraw, B M; Pennock, P; Ducharme, N G; Baird, J D

1986-03-01

Twenty pony foals (reared worm free), 6.5 to 10 weeks of age, were inoculated with Strongylus vulgaris and allocated to 5 groups, each with 4 foals. One week after inoculation, 1 group of 4 foals was given oxfendazole (OFZ) at a dosage rate of 10 mg/kg of body weight, another group was given 2 such treatments 48 hours apart, and a 3rd group was given a placebo. All treatments were administered by stomach tube. Three weeks later, foals were euthanatized and necropsied in a test for efficacy against early 4th-stage larvae. Oxfendazole was 80% and 94.9% effective against early 4th-stage S vulgaris with 1 and 2 doses, respectively. A 4th group of 4 foals was given 2 treatments of OFZ, 48 hours apart, about 8 weeks after inoculation, and a 5th group was given a placebo. These foals were euthanatized and necropsied 5 weeks after treatment in a test for efficacy against later 4th-stage larvae. Two doses of OFZ were 96.6% effective against later 4th-stage larvae.

The Hyalella (Crustacea: Amphipoda) species cloud of the ancient Lake Titicaca originated from multiple colonizations.

Science.gov (United States)

Adamowicz, Sarah J; Marinone, María Cristina; Menu-Marque, Silvina; Martin, Jeffrey W; Allen, Daniel C; Pyle, Michelle N; De Los Ríos, Patricio; Sobel, Crystal N; Ibañez, Carla; Pinto, Julio; Witt, Jonathan D S

2018-08-01

Ancient lakes are renowned for their exceptional diversity of endemic species. As model systems for the study of sympatric speciation, it is necessary to understand whether a given hypothesized species flock is of monophyletic or polyphyletic origin. Here, we present the first molecular characterization of the Hyalella (Crustacea: Amphipoda) species complex of Lake Titicaca, using COI and 28S DNA sequences, including samples from the connected Small and Large Lakes that comprise Lake Titicaca as well as from a broader survey of southern South American sites. At least five evolutionarily distant lineages are present within Lake Titicaca, which were estimated to have diverged from one another 12-20 MYA. These major lineages are dispersed throughout the broader South American Hyalella phylogeny, with each lineage representing at least one independent colonization of the lake. Moreover, complex genetic relationships are revealed between Lake Titicaca individuals and those from surrounding water bodies, which may be explained by repeated dispersal into and out of the lake, combined with parallel intralacustrine diversification within two separate clades. Although further work in deeper waters will be required to determine the number of species present and modes of diversification, our results strongly indicate that this amphipod species cloud is polyphyletic with a complex geographic history. Copyright © 2018 Elsevier Inc. All rights reserved.

4(1H)-Pyridone and 4(1H)-Quinolone Derivatives as Antimalarials with Erythrocytic, Exoerythrocytic, and Transmission Blocking Activities

Science.gov (United States)

Monastyrskyi, Andrii; Kyle, Dennis E.; Manetsch, Roman

2015-01-01

Infectious diseases are the second leading cause of deaths in the world with malaria being responsible for approximately the same amount of deaths as cancer in 2012. Despite the success in malaria prevention and control measures decreasing the disease mortality rate by 45% since 2000, the development of single-dose therapeutics with radical cure potential is required to completely eradicate this deadly condition. Targeting multiple stages of the malaria parasite is becoming a primary requirement for new candidates in antimalarial drug discovery and development. Recently, 4(1H)-pyridone, 4(1H)-quinolone, 1,2,3,4-tetrahydroacridone, and phenoxyethoxy-4(1H)-quinolone chemotypes have been shown to be antimalarials with blood stage activity, liver stage activity, and transmission blocking activity. Advancements in structure-activity relationship and structure-property relationship studies, biological evaluation in vitro and in vivo, as well as pharmacokinetics of the 4(1H)-pyridone and 4(1H)-quinolone chemotypes will be discussed. PMID:25116582

Three-stage linear, split-Stirling cryocooler for 1 to 2K magnetic cold stage

International Nuclear Information System (INIS)

Longsworth, R.C.

1993-08-01

A long-life, linear, high efficiency 8K split Stirling cycle cryocooler was designed, built, and tested. The refrigerator is designed for cooling a 50 mW, 1.5K magnetic cold stage. Dual opposed piston compressors are driven by moving-coil linear motors. The three stage expander, although not completed, is also driven by a linear motor and is designed to produce 1 SW at 60K, 4W at 16K, and 1.2W at 8K. The cold regenerator employs a parallel gap construction for high efficiency. The key technology areas addressed include warm and cold flexible suspension bearings and a new cold regenerator geometry for high efficiency at 8K

Pod-1/Capsulin shows a sex- and stage-dependent expression pattern in the mouse gonad development and represses expression of Ad4BP/SF-1.

Science.gov (United States)

Tamura, M; Kanno, Y; Chuma, S; Saito, T; Nakatsuji, N

2001-04-01

Mammalian sex-determination and differentiation are controlled by several genes, such as Sry, Sox-9, Dax-1 and Mullerian inhibiting substance (MIS), but their upstream and downstream genes are largely unknown. Ad4BP/SF-1, encoding a zinc finger transcription factor, plays important roles in gonadogenesis. Disruption of this gene caused disappearance of the urogenital system including the gonad. Ad4BP/SF-1, however, is also involved in the sex differentiation of the gonad at later stages, such as the regulation of steroid hormones and MIS. Pod-1/Capsulin, a member of basic helix-loop-helix transcription factors, is expressed in a pattern closely related but mostly complimentary to that of the Ad4BP/SF-1 expression in the developing gonad. In the co-transfection experiment using cultured cells, overexpression of Pod-1/Capsulin repressed expression of a reporter gene that carried the upstream regulatory region of the Ad4BP/SF-1 gene. Furthermore, forced expression of Pod-1/Capsulin repressed expression of Ad4BP/SF-1 in the Leydig cell-derived I-10 cells. These results suggest that Pod-1/Capsulin may play important roles in the development and sex differentiation of the mammalian gonad via transcriptional regulation of Ad4BP/SF-1.

Core compressor exit stage study. 1: Aerodynamic and mechanical design

Science.gov (United States)

Burdsall, E. A.; Canal, E., Jr.; Lyons, K. A.

1979-01-01

The effect of aspect ratio on the performance of core compressor exit stages was demonstrated using two three stage, highly loaded, core compressors. Aspect ratio was identified as having a strong influence on compressors endwall loss. Both compressors simulated the last three stages of an advanced eight stage core compressor and were designed with the same 0.915 hub/tip ratio, 4.30 kg/sec (9.47 1bm/sec) inlet corrected flow, and 167 m/sec (547 ft/sec) corrected mean wheel speed. The first compressor had an aspect ratio of 0.81 and an overall pressure ratio of 1.357 at a design adiabatic efficiency of 88.3% with an average diffusion factor or 0.529. The aspect ratio of the second compressor was 1.22 with an overall pressure ratio of 1.324 at a design adiabatic efficiency of 88.7% with an average diffusion factor of 0.491.

Stage 4S neuroblastoma, a disseminated tumor with excellent outcome

International Nuclear Information System (INIS)

Elimam, Najla A.; Atra, Ayad A.; Fayea, Najwa Y.; Al-Asaad, Tareq G.; Khattab, Taha M.; Al-Sulami, Ganadeel A.; Felimban, Sami K.

2006-01-01

To review the clinical features and outcome of all cases of stage 4S neuroblastoma treated at our center. We retrospectively reviewed the files of all patients (n=75) with neuroblastoma treated at King Abdul-Aziz Medical City, Jeddah, Kingdom of Saudi Arabia between 1986 and 2005. We studied the clinical features and outcome of patients with stage 4S neuroblastoma. Six patients (8%) were confirmed to have stage 4S neuroblastoma. Three were boys with a median age at diagnosis of 4.5 months (range 28 days-11 moths). Four patients required no intervention. The remaining 2 patients were treated chemotherapy due to progressive hepatomegaly and respiratory distress. No patient required radiotherapy or surgical intervention. With a median follow up of four years (range 9 months --- 15.5 years), all patients are alive and well. Two patients continue to have a residual abdominal mass, while complete resolution occurred in the others. Stage 4S neuroblastoma is special tumor that carries excellent prognosis. Spontaneous regression may occur and intervention is only required in symptomatic patients. (author)

Enhanced Production of Androst-1,4-Diene-3,17-Dione by Mycobacterium neoaurum JC-12 Using Three-Stage Fermentation Strategy

Science.gov (United States)

Shao, Minglong; Zhang, Xian; Rao, Zhiming; Xu, Meijuan; Yang, Taowei; Li, Hui; Xu, Zhenghong

2015-01-01

To improve the androst-1,4-diene-3,17-dione (ADD) production from phytosterol by Mycobacterium neoaurum JC-12, fructose was firstly found favorable as the initial carbon source to increase the biomass and eliminate the lag phase of M. neoaurum JC-12 in the phytosterol transformation process. Based on this phenomenon, two-stage fermentation by using fructose as the initial carbon source and feeding glucose to maintain strain metabolism was designed. By applying this strategy, the fermentation duration was decreased from 168 h to 120 h with the ADD productivity increased from 0.071 g/(L·h) to 0.108 g/(L·h). Further, three-stage fermentation by adding phytosterol to improve ADD production at the end of the two-stage fermentation was carried out and the final ADD production reached 18.6 g/L, which is the highest reported ADD production using phytosterol as substrate. Thus, this strategy provides a possible way in enhancing the ADD production in pharmaceutical industry. PMID:26352898

Enhanced Production of Androst-1,4-Diene-3,17-Dione by Mycobacterium neoaurum JC-12 Using Three-Stage Fermentation Strategy.

Directory of Open Access Journals (Sweden)

Minglong Shao

Full Text Available To improve the androst-1,4-diene-3,17-dione (ADD production from phytosterol by Mycobacterium neoaurum JC-12, fructose was firstly found favorable as the initial carbon source to increase the biomass and eliminate the lag phase of M. neoaurum JC-12 in the phytosterol transformation process. Based on this phenomenon, two-stage fermentation by using fructose as the initial carbon source and feeding glucose to maintain strain metabolism was designed. By applying this strategy, the fermentation duration was decreased from 168 h to 120 h with the ADD productivity increased from 0.071 g/(L·h to 0.108 g/(L·h. Further, three-stage fermentation by adding phytosterol to improve ADD production at the end of the two-stage fermentation was carried out and the final ADD production reached 18.6 g/L, which is the highest reported ADD production using phytosterol as substrate. Thus, this strategy provides a possible way in enhancing the ADD production in pharmaceutical industry.

Clinical potentials of methylator phenotype in stage 4 high-risk neuroblastoma: an open challenge.

Directory of Open Access Journals (Sweden)

Barbara Banelli

Full Text Available Approximately 20% of stage 4 high-risk neuroblastoma patients are alive and disease-free 5 years after disease onset while the remaining experience rapid and fatal progression. Numerous findings underline the prognostic role of methylation of defined target genes in neuroblastoma without taking into account the clinical and biological heterogeneity of this disease. In this report we have investigated the methylation of the PCDHB cluster, the most informative member of the "Methylator Phenotype" in neuroblastoma, hypothesizing that if this epigenetic mark can predict overall and progression free survival in high-risk stage 4 neuroblastoma, it could be utilized to improve the risk stratification of the patients, alone or in conjunction with the previously identified methylation of the SFN gene (14.3.3sigma that can accurately predict outcome in these patients. We have utilized univariate and multivariate models to compare the prognostic power of PCDHB methylation in terms of overall and progression free survival, quantitatively determined by pyrosequencing, with that of other markers utilized for the patients' stratification utilizing methylation thresholds calculated on neuroblastoma at stage 1-4 and only on stage 4, high-risk patients. Our results indicate that PCDHB accurately distinguishes between high- and intermediate/low risk stage 4 neuroblastoma in agreement with the established risk stratification criteria. However PCDHB cannot predict outcome in the subgroup of stage 4 patients at high-risk whereas methylation levels of SFN are suggestive of a "methylation gradient" associated with tumor aggressiveness as suggested by the finding of a higher threshold that defines a subset of patients with an extremely severe disease (OS <24 months. Because of the heterogeneity of neuroblastoma we believe that clinically relevant methylation markers should be selected and tested on homogeneous groups of patients rather than on patients at all stages.

Homeobox protein MSX-1 inhibits expression of bone morphogenetic protein 2, bone morphogenetic protein 4, and lymphoid enhancer-binding factor 1 via Wnt/β-catenin signaling to prevent differentiation of dental mesenchymal cells during the late bell stage.

Science.gov (United States)

Feng, Xiao-Yu; Wu, Xiao-Shan; Wang, Jin-Song; Zhang, Chun-Mei; Wang, Song-Lin

2018-02-01

Homeobox protein MSX-1 (hereafter referred to as MSX-1) is essential for early tooth-germ development. Tooth-germ development is arrested at bud stage in Msx1 knockout mice, which prompted us to study the functions of MSX-1 beyond this stage. Here, we investigated the roles of MSX-1 during late bell stage. Mesenchymal cells of the mandibular first molar were isolated from mice at embryonic day (E)17.5 and cultured in vitro. We determined the expression levels of β-catenin, bone morphogenetic protein 2 (Bmp2), Bmp4, and lymphoid enhancer-binding factor 1 (Lef1) after knockdown or overexpression of Msx1. Our findings suggest that knockdown of Msx1 promoted expression of Bmp2, Bmp4, and Lef1, resulting in elevated differentiation of odontoblasts, which was rescued by blocking the expression of these genes. In contrast, overexpression of Msx1 decreased the expression of Bmp2, Bmp4, and Lef1, leading to a reduction in odontoblast differentiation. The regulation of Bmp2, Bmp4, and Lef1 by Msx1 was mediated by the Wnt/β-catenin signaling pathway. Additionally, knockdown of Msx1 impaired cell proliferation and slowed S-phase progression, while overexpression of Msx1 also impaired cell proliferation and prolonged G1-phase progression. We therefore conclude that MSX-1 maintains cell proliferation by regulating transition of cells from G1-phase to S-phase and prevents odontoblast differentiation by inhibiting expression of Bmp2, Bmp4, and Lef1 at the late bell stage via the Wnt/β-catenin signaling pathway. © 2017 Eur J Oral Sci.

Overt hypoadrenalism is uncommon in patients with stage 3 and 4 ...

African Journals Online (AJOL)

Our study aimed to determine the prevalence of primary hypoadrenalism, as defined by a subnormal cortisol response to the 250 µg adrenocorticotrophic hormone (ACTH) stimulation test, in patients with stage 3 and 4 lung cancer. Methods. Thirty patients with stage 3 and 4 bronchogenic carcinoma were prospectively ...

Prevalence of secondary hyperparathyroidism in patients with stage 3 and 4 chronic kidney disease seen in internal medicine.

Science.gov (United States)

Bureo, Juan Carlos; Arévalo, Jose Carlos; Antón, Joaquín; Adrados, Gaspar; Jiménez Morales, Jose Luis; Robles, Nicolás Roberto

2015-01-01

Despite the high prevalence of chronic kidney disease in the elderly population, few data are available on the frequency of secondary hyperparathyroidism in the Spanish population affected by this problem. We undertook a study on this issue in patients attending the internal medicine departments in our area. An observational, cross-sectional survey performed at internal medicine departments on 415 patients with stage 3 and 4 chronic kidney disease. Clinical history and risk factors were collected using a standardized protocol. Serum creatinine, phosphate, calcium, intact parathormone (PTH) and 25-hydroxy-cholecalciferol (25-OH-vitD) levels were measured in all patients. Among stage 3 patients, 62.9% had PTH levels ≥70pg/mL and 32.7% levels ≥110pg/mL. Median PTH level in stage 4 patients was 120pg/mL (p <0.001), and 77.9% of these patients had PTH ≥70pg/mL (p <0.001) and 54.1% ≥110pg/mL (p=0.015). Adequate 25-hydroxy-cholecalciferol levels were found in only 7.2% of stage 3 patients and 4.1% of stage 4 patients. Only 7.2% of stage 3 patients had hyperphosphatemia, as compared to 25.4% of stage 4 patients (p <0.001). Hyperparathyroidism is a common complication of stage 3 and 4 chronic kidney disease which is not associated to detectable changes in serum calcium and phosphate levels. It is therefore advisable to measure PTH levels in all patients with decreased glomerular filtration rate. Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

4D atlas of the mouse embryo for precise morphological staging.

Science.gov (United States)

Wong, Michael D; van Eede, Matthijs C; Spring, Shoshana; Jevtic, Stefan; Boughner, Julia C; Lerch, Jason P; Henkelman, R Mark

2015-10-15

After more than a century of research, the mouse remains the gold-standard model system, for it recapitulates human development and disease and is quickly and highly tractable to genetic manipulations. Fundamental to the power and success of using a mouse model is the ability to stage embryonic mouse development accurately. Past staging systems were limited by the technologies of the day, such that only surface features, visible with a light microscope, could be recognized and used to define stages. With the advent of high-throughput 3D imaging tools that capture embryo morphology in microscopic detail, we now present the first 4D atlas staging system for mouse embryonic development using optical projection tomography and image registration methods. By tracking 3D trajectories of every anatomical point in the mouse embryo from E11.5 to E14.0, we established the first 4D atlas compiled from ex vivo 3D mouse embryo reference images. The resulting 4D atlas comprises 51 interpolated 3D images in this gestational range, resulting in a temporal resolution of 72 min. From this 4D atlas, any mouse embryo image can be subsequently compared and staged at the global, voxel and/or structural level. Assigning an embryonic stage to each point in anatomy allows for unprecedented quantitative analysis of developmental asynchrony among different anatomical structures in the same mouse embryo. This comprehensive developmental data set offers developmental biologists a new, powerful staging system that can identify and compare differences in developmental timing in wild-type embryos and shows promise for localizing deviations in mutant development. © 2015. Published by The Company of Biologists Ltd.

Expression of OCT4A: The First Step to the Next Stage of Urothelial Bladder Cancer Progression

Directory of Open Access Journals (Sweden)

Wojciech Jóźwicki

2014-09-01

Full Text Available OCT4 (octamer-binding transcription factor is a transcription factor responsible for maintaining the pluripotent properties of embryonic stem cells. In this paper, we present the results of studies to investigate the role of the OCT4 splicing variant in urothelial bladder cancer and the relationship between the OCT4 phenotype and the morphological parameters of tumor malignancy. Ninety patients who received a cystectomy for bladder cancer were enrolled. The expression of OCT4 protein was analyzed by immunohistochemistry. The ratio of OCT4-positive cells was the lowest in pT1 (pathological assessment (p—tumor extent confined to mucosa (T1 tumors and the highest in pTis (non-papillary tumor extent confined to urothelium and pT2 (tumor extent including muscularis propria tumors. Information about the percentage of OCT4A-positive tumor cells could facilitate choosing the treatment mode in borderline pTis–pT1 (crossing the border of the basement membrane; the first stage of progression and pT1–pT2 (crossing the border of the muscularis propria; the second stage of progression cases: a higher percentage of OCT4A-positive cells should support more radical therapy. A significantly higher percentage of cases with moderate OCT4 intensity was found in metastasizing (the third stage of progression cases with >2 positive lymph nodes. The percentage of OCT4-positive cells was significantly higher for cancers with a high grade, higher non-classic differentiation number and greater aggressiveness of invasion. The differentiation, maturation and aggressiveness of tumor invasion appear to depend on the expression of the OCT4 phenotype in cancer cells, similar to the successive stages of malignancy progression in urothelial cancer.

Early two-stage double opposing Z-plasty or one-stage push-back palatoplasty?: comparisons in maxillary development and speech outcome at 4 years of age.

Science.gov (United States)

Yamanishi, Tadashi; Nishio, Juntaro; Sako, Michiyo; Kohara, Hiroshi; Hirano, Yoshiko; Yamanishi, Yukiko; Adachi, Tadafumi; Miya, Shigenori; Mukai, Takao

2011-02-01

Determining the optimal timing and procedure of palatal surgery for children with cleft lip and palate has long raised a major controversy. An early two-stage palatoplasty protocol has been a recent trend in an attempt to obtain preferable maxillary growth without compromising adequate speech development. In this study, we aim to address whether the resulting maxillofacial growth and speech development obtained by an early 2-stage palatoplasty protocol are better than those obtained by conventional 1-stage push-back palatoplasty. Seventy-two nonsyndromic children with complete unilateral cleft lip and palate were enrolled in this study. They were divided into 2 groups: 30 children, who were treated with early 2-stage palatoplasty, in which soft palate closure was performed using a modified Furlow's procedure at 12 months of age and hard palate closure was performed at 18 months of age (Early Tow Stage [ETS] group: 22 boys, 8 girls), and 42 children, who underwent 1-stage Wardill-Kilner push-back palatoplasty at 12 months of age (Push Back [PB] group: 31 boys, 11 girls). Cephalometric analysis for maxillofacial growth and assessments of speech development were performed for each child at 4 years of age. The ETS group showed a lager maxillary length than the PB group [anterior nasal spine (ANS)-ptm': ETS, 46.7 ± 2.0 mm; PB, 43.6 ± 2.3 mm]. The ANS in the ETS group was positioned more anteriorly than that in the PB group (N'-ANS: ETS, 2.5 ± 1.8 mm; PB, 0.26 ± 2.5 mm), whereas the posterior edge of the maxilla positioned anteroposteiorly was comparable between the 2 groups. The anterior facial height was significantly greater in the ETS group than in the PB group (N-N': ETS, 43.3 ± 2.9 mm; PB, 40.1 ± 2.3 mm, S-S': ETS, 29.7 ± 3.2 mm; PB, 31.0 ± 3.2 mm). No statistically significant differences were observed in the incidence of either velopharyngeal incompetence or articulation errors between the 2 groups at 4 years of age. Our results show that the early 2

CDC staging based on absolute CD4 count and CD4 percentage in an HIV-1-infected Indian population: treatment implications

Science.gov (United States)

Vajpayee, M; Kaushik, S; Sreenivas, V; Wig, N; Seth, P

2005-01-01

CD4+ T-cell levels are an important criterion for categorizing HIV-related clinical conditions according to the CDC classification system and are therefore important in the management of HIV by initiating antiretroviral therapy and prophylaxis for opportunistic infections due to HIV among HIV-infected individuals. However, it has been observed that the CD4 counts are affected by the geographical location, race, ethnic origin, age, gender and changes in total and differential leucocyte counts. In the light of this knowledge, we classified 600 HIV seropositive antiretroviral treatment (ART)-naïve Indian individuals belonging to different CDC groups A, B and C on the basis of CDC criteria of both CD4% and CD4 counts and receiver operating characteristic (ROC) curves were generated. Importantly, CDC staging on the basis of CD4% indicated significant clinical implications, requiring an early implementation of effective antiretroviral treatment regimen in HIV-infected individuals deprived of treatment when classified on the basis of CD4 counts. PMID:16045738

Immature murine NKT cells pass through a stage of developmentally programmed innate IL-4 secretion

Science.gov (United States)

Dickgreber, Nina; Farrand, Kathryn J.; van Panhuys, Nicholas; Knight, Deborah A.; McKee, Sara J.; Chong, Mei L.; Miranda-Hernandez, Socorro; Baxter, Alan G.; Locksley, Richard M.; Le Gros, Graham; Hermans, Ian F.

2012-01-01

We assessed the production of the canonical Th2 cytokine IL-4 by NKT cells directly in vivo using IL-4-substituting strains of reporter mice that provide faithful and sensitive readouts of cytokine production without the confounding effects of in vitro stimulation. Analysis in naïve animals revealed an “innate” phase of IL-4 secretion that did not need to be triggered by administration of a known NKT cell ligand. This secretion was by immature NKT cells spanning Stage 1 of the maturation process in the thymus (CD4+ CD44lo NK1.1− cells) and Stage 2 (CD4+ CD44hi NK1.1− cells) in the spleen. Like ligand-induced IL-4 production by mature cells, this innate activity was independent of an initial source of IL-4 protein and did not require STAT6 signaling. A more sustained level of innate IL-4 production was observed in animals on a BALB/c background compared with a C57BL/6 background, suggesting a level of genetic regulation that may contribute to the “Th2-prone” phenotype in BALB/c animals. These observations indicate a regulated pattern of IL-4 expression by maturing NKT cells, which may endow these cells with a capacity to influence the development of surrounding cells in the thymus. PMID:22941735

Bilateral hip arthroplasty: is 1-week staging the optimum strategy?

Directory of Open Access Journals (Sweden)

Willis-Owen Charles A

2010-11-01

Full Text Available Abstract Seventy-nine patients underwent bilateral hip arthroplasty staged either at 1 week (Group 1 or after greater intervals (as suggested by the patients, mean 44 weeks, range 16-88 weeks (Group 2, over a five year period at one Institution. Sixty-eight patients (29 bilateral hip resurfacings and 39 total hip replacements completed questionnaires regarding their post-operative recovery, complications and overall satisfaction with the staging of their surgery. There was no significant age or ASA grade difference between the patient groups. Complication rates in the two groups were similar and overall satisfaction rates were 84% in Group 1 (n = 32 and 89% in Group 2 (n = 36. Cumulative hospital lengths of stay were significantly longer in Group 1 patients (11.9 days vs 9.1 days(p The mean time to return to part-time work was 16.4 weeks for Group 1, and a cumulative 17.2 weeks (8.8 and 8.4 weeks for Group 2. The time to return to full-time work was significantly shorter for Group 1 patients (21.0 weeks, compared with a cumulative 29.7 weeks for Group 2(p Hip resurfacing patients in Group 2 had significantly shorter durations of postoperative pain and were able to return to part-time and full time work sooner than total hip arthroplasty patients. There was a general trend towards a faster recovery and resumption of normal activities following the second operation in Group 2 patients, compared with the first operation. Bilateral hip arthroplasty staged at a 1-week interval resulted in an earlier resolution of hip pain, and an earlier return to full-time work (particularly following total hip replacement surgery, with high levels of patient satisfaction and no increased risk in complications; however the hospital length of stay was significantly longer. The decision for the timing of staged bilateral surgery should be made in conjunction with the patient, making adjustments to accommodate their occupational needs and functional demands.

Interleukin-4 receptor alpha overexpression in human bladder cancer correlates with the pathological grade and stage of the disease

International Nuclear Information System (INIS)

Joshi, Bharat H; Leland, Pamela; Lababidi, Samir; Varrichio, Frederick; Puri, Raj K

2014-01-01

Previously, we have demonstrated that interleukin-4 receptor α (IL-4Rα) is overexpressed on a variety of human cancers and can serve as target for IL-4 immunotoxin comprised of IL-4 and a mutated Pseudomonas exotoxin. However, its expression and association with grade and clinical stage of bladder cancer has not been studied. IL-4Rα expression was examined in human bladder cancer cell lines, mouse xenografts, and biopsy specimens at mRNA and protein levels by real-time RT-PCR and IHC/ISH techniques. We also examined the effect of IL-4 on proliferation and invasion of bladder carcinoma cell lines. For tissue microarray (TMA) results, we analyzed the precision data using exact binomial proportion with exact two-sided P-values. We used Cochran–Armitage Statistics with exact two-sided P-values to examine the trend analysis of IL-4Rα over grade or stage of the bladder cancer specimens. The influence of age and gender covariates was also analyzed using multiple logistic regression models. IL-4Rα is overexpressed in five bladder cancer cell lines, while normal bladder and human umbilical vein cell lines (HUVEC) expressed at low levels. Two other chains of IL-4 receptor complex, IL-2RγC and IL-13Rα1, were absent or weakly expressed. IL-4 modestly inhibited the cell proliferation, but enhanced cell invasion of bladder cancer cell lines in a concentration-dependent manner. Bladder cancer xenografts in immunodeficient mice also maintained IL-4Rα overexpression in vivo. Analysis of tumor biopsy specimens in TMAs revealed significantly higher IL-4Rα immunostaining (≥2+) in Grade 2 (85%) and Grade 3 (97%) compared to Grade 1 tumors (0%) (P ≤ 0.0001). Similarly, 9% stage I tumors were positive for IL-4Rα (≥2+) compared to 84% stage II (P ≤ 0.0001) and 100% stages III–IV tumors (P ≤ 0.0001). IL-13Rα1 was also expressed in tumor tissues but at low levels and it did not show any correlation with the grade and stage of disease. However, the IL-2RγC was not

T4 category revision enhances the accuracy and significance of stage III breast cancer.

Science.gov (United States)

Güth, Uwe; Singer, Gad; Langer, Igor; Schötzau, Andreas; Herberich, Linda; Holzgreve, Wolfgang; Wight, Edward

2006-06-15

Because of the considerable heterogeneity in breast carcinoma with noninflammatory skin involvement (T4b/Stage IIIB), a revision was proposed of the TNM staging system that would classify these tumors exclusively based on their tumor size and lymph node status. In the current study, the authors evaluated how implementation of this proposal will affect Stage III noninflammatory breast cancer. Two hundred seven patients who were classified with noninflammatory Stage III breast cancer were treated consecutively between 1990 and 1999 at the University Hospital Basel, Switzerland. To assess the extent of T4b/Stage IIIB tumors independent of the clinicopathologic feature of skin involvement, the reclassification was undertaken. Of 68 patients who had nonmetastatic T4b breast cancer, 37 patients (54.4%) had a tumor extent in accordance with Stage I/II and had improved disease-specific survival (DSS) compared with patients who had Stage III breast cancer (P = .008). Excluding those patients from Stage III led to a 17.9% reduction of the number of patients in this group (n = 170 patients). The 10-year DSS declined from 48.5% to 42.9%. Considerable numbers of patients who are classified with noninflammatory Stage IIIB breast cancer show only a limited disease extent. Through a revision of the T4 category, these low-risk patients were excluded from the highest nonmetastatic TNM stage, and overstaging could be avoided. This procedure decreased the degree of heterogeneity of the entire Stage III group and may result in a more precise assessment of this disease entity. Copyright 2006 American Cancer Society.

Visual Outcome after Laser Photocoagulation for Stage 4 ...

African Journals Online (AJOL)

Objective: The objectives of this research is to evaluate the visual outcome after peripheral laser photo-coagulation for Goldberg stage-4 proliferative sickle cell retinopathy patients seen in Eye Foundation Hospital Lagos between January and December 2002. Methodology: A hospital-based retrospective case review study ...

A 5.4mW GPS CMOS quadrature front-end based on a single-stage LNA-mixer-VCO

DEFF Research Database (Denmark)

Liscidini, Amtonio; Mazzanti, Andrea; Tonietto, Riccardo

2006-01-01

A GPS RF front-end combines the LNA, mixer, and VCO in a single stage and can operate from a 1.2V supply. The chip is implemented in a 0.13um CMOS process and occupies 1.5mm2 active area. It consumes 5.4mW with a 4.8dB NF, 36dB gain, and a P1dB of -31dBm.......A GPS RF front-end combines the LNA, mixer, and VCO in a single stage and can operate from a 1.2V supply. The chip is implemented in a 0.13um CMOS process and occupies 1.5mm2 active area. It consumes 5.4mW with a 4.8dB NF, 36dB gain, and a P1dB of -31dBm....

Serum insulin-like growth factor-1 levels in females and males in different cervical vertebral maturation stages

Science.gov (United States)

Gupta, Shreya; Deoskar, Anuradha; Gupta, Puneet; Jain, Sandhya

2015-01-01

OBJECTIVE: The aim of this cross sectional study was to assess serum insulin-like growth factor-1 (IGF-1) levels in female and male subjects at various cervical vertebral maturation (CVM) stages. MATERIAL AND METHODS: The study sample consisted of 60 subjects, 30 females and 30 males, in the age range of 8-23 years. For all subjects, serum IGF-1 level was estimated from blood samples by means of chemiluminescence immunoassay (CLIA). CVM was assessed on lateral cephalograms using the method described by Baccetti. Serum IGF-1 level and cervical staging data of 30 female subjects were included and taken from records of a previous study. Data were analyzed by Kruska-Wallis and Mann Whitney test. Bonferroni correction was carried out and alpha value was set at 0.003. RESULTS: Peak value of serum IGF-1 was observed in cervical stages CS3 in females and CS4 in males. Differences between males and females were observed in mean values of IGF-1 at stages CS3, 4 and 5. The highest mean IGF-1 levels in males was observed in CS4 followed by CS5 and third highest in CS3; whereas in females the highest mean IGF-1 levelswas observed in CS3 followed by CS4 and third highest in CS5. Trends of IGF-1 in relation to the cervical stages also differed between males and females. The greatest mean serum IGF-1 value for both sexes was comparable, for females (397 ng/ml) values were slightly higher than in males (394.8 ng/ml). CONCLUSIONS: Males and females showed differences in IGF-1 trends and levels at different cervical stages. PMID:25992990

Serum insulin-like growth factor-1 levels in females and males in different cervical vertebral maturation stages.

Science.gov (United States)

Gupta, Shreya; Deoskar, Anuradha; Gupta, Puneet; Jain, Sandhya

2015-01-01

The aim of this cross sectional study was to assess serum insulin-like growth factor-1 (IGF-1) levels in female and male subjects at various cervical vertebral maturation (CVM) stages. The study sample consisted of 60 subjects, 30 females and 30 males, in the age range of 8-23 years. For all subjects, serum IGF-1 level was estimated from blood samples by means of chemiluminescence immunoassay (CLIA). CVM was assessed on lateral cephalograms using the method described by Baccetti. Serum IGF-1 level and cervical staging data of 30 female subjects were included and taken from records of a previous study. Data were analyzed by Kruska-Wallis and Mann Whitney test. Bonferroni correction was carried out and alpha value was set at 0.003. Peak value of serum IGF-1 was observed in cervical stages CS3 in females and CS4 in males. Differences between males and females were observed in mean values of IGF-1 at stages CS3, 4 and 5. The highest mean IGF-1 levels in males was observed in CS4 followed by CS5 and third highest in CS3; whereas in females the highest mean IGF-1 levelswas observed in CS3 followed by CS4 and third highest in CS5. Trends of IGF-1 in relation to the cervical stages also differed between males and females. The greatest mean serum IGF-1 value for both sexes was comparable, for females (397 ng/ml) values were slightly higher than in males (394.8 ng/ml). Males and females showed differences in IGF-1 trends and levels at different cervical stages.

Mechanical Design of a 4-Stage ADR for the PIPER mission

Science.gov (United States)

James, Bryan L.; Kimball, Mark O.; Shirron, Peter J.; Sampson, Michael A.; Letmate, Richard V.; Jackson, Michael L.

2017-01-01

The four 1,280 bolometer detector arrays that will fly on the balloon borne PIPER mission will be cooled by a 4-stage adiabatic demagnetization refrigerator (ADR). Two of the three mechanically independent ADR assemblies provide thermal isolation to their salt pills through Kevlar suspensions while the other provides thermal isolation to its salt pill through the use of bellows and Vespel material. The ADR integrates with the detector arrays and it sits in a large bucket Dewar containing superfluid liquid helium. This paper will describe the complex mechanical design of the PIPER ADR, and summarize the mechanical analysis done to validate the design.The four 1,280 bolometer detector arrays that will fly on the balloon borne PIPER mission will be cooled by a 4-stage adiabatic demagnetization refrigerator (ADR). Two of the three mechanically independent ADR assemblies provide thermal isolation to their salt pills through Kevlar suspensions while the other provides thermal isolation to its salt pill through the use of bellows and Vespel material. The ADR integrates with the detector arrays and it sits in a large bucket Dewar containing superfluid liquid helium. This paper will describe the complex mechanical design of the PIPER ADR, and summarize the mechanical analysis done to validate the design.

Interleukin-4 receptor alpha overexpression in human bladder cancer correlates with the pathological grade and stage of the disease.

Science.gov (United States)

Joshi, Bharat H; Leland, Pamela; Lababidi, Samir; Varrichio, Frederick; Puri, Raj K

2014-12-01

Previously, we have demonstrated that interleukin-4 receptor α (IL-4Rα) is overexpressed on a variety of human cancers and can serve as target for IL-4 immunotoxin comprised of IL-4 and a mutated Pseudomonas exotoxin. However, its expression and association with grade and clinical stage of bladder cancer has not been studied. IL-4Rα expression was examined in human bladder cancer cell lines, mouse xenografts, and biopsy specimens at mRNA and protein levels by real-time RT-PCR and IHC/ISH techniques. We also examined the effect of IL-4 on proliferation and invasion of bladder carcinoma cell lines. For tissue microarray (TMA) results, we analyzed the precision data using exact binomial proportion with exact two-sided P-values. We used Cochran-Armitage Statistics with exact two-sided P-values to examine the trend analysis of IL-4Rα over grade or stage of the bladder cancer specimens. The influence of age and gender covariates was also analyzed using multiple logistic regression models. IL-4Rα is overexpressed in five bladder cancer cell lines, while normal bladder and human umbilical vein cell lines (HUVEC) expressed at low levels. Two other chains of IL-4 receptor complex, IL-2RγC and IL-13Rα1, were absent or weakly expressed. IL-4 modestly inhibited the cell proliferation, but enhanced cell invasion of bladder cancer cell lines in a concentration-dependent manner. Bladder cancer xenografts in immunodeficient mice also maintained IL-4Rα overexpression in vivo. Analysis of tumor biopsy specimens in TMAs revealed significantly higher IL-4Rα immunostaining (≥ 2+) in Grade 2 (85%) and Grade 3 (97%) compared to Grade 1 tumors (0%) (P ≤ 0.0001). Similarly, 9% stage I tumors were positive for IL-4Rα (≥ 2+) compared to 84% stage II (P ≤ 0.0001) and 100% stages III-IV tumors (P ≤ 0.0001). IL-13Rα1 was also expressed in tumor tissues but at low levels and it did not show any correlation with the grade and stage of disease. However, the IL-2RγC was not

Hybrid palliation for critical systemic outflow obstruction: neither rapid stage 1 Norwood nor comprehensive stage 2 mitigate consequences of early risk factors.

Science.gov (United States)

Davies, Ryan R; Radtke, Wolfgang; Bhat, Majeed A; Baffa, Jeanne M; Woodford, Edward; Pizarro, Christian

2015-01-01

Hybrid palliation with branch pulmonary artery banding (bPAB) has become increasingly common in the early management of patients with critical left ventricular outflow obstruction. Optimal subsequent surgical palliation remains undefined. We retrospectively reviewed patients undergoing initial bPAB for single ventricle physiology with systemic outflow obstruction (2001-2013, n = 37). Patients were stratified by subsequent surgical palliation: stage 1 Norwood (St1N, n = 14), comprehensive stage 2 (CompSt2, n = 11), and none (n = 12). bPAB was performed at a median of 4 days and 2.7-kg, post-bPAB mortality was increased in patients with aortic atresia (odds ratio [OR] = 3.8, 95% confidence interval [CI] = 0.9-15.8) or birth weight <2 kg (OR = 13.8, 95% CI = 1.4-136.4). Palliation strategy did not affect transplant-free survival through second-stage palliation (St1N: 71.4%, CompSt2: 72.7%, P = .9). Among CompSt2 patients, there was a trend toward poorer survival with aortic atresia (0% vs 80%, P = .09); birth weight <2.5 kg was associated with decreased survival (0% vs 89.0%, P = .01). A trend toward lower survival with low birth weight was evident among St1N patients (<2 kg, OR = 0.1, 95% CI = 0.01-1.9, P = .09). CompSt2 mortality occurred on postoperative days 0 and 1. Mortality following St1N occurred at a median of 38.5 days (range = 23.5-104.5). Among survivors of stage 2 palliation, Fontan completion was performed in the same number of patients in each group (St1N: 6/8, 75%, CompSt2: 6/8, 75%). Both St1N and CompSt2 are viable options for subsequent palliation following initial hybrid procedure. Transplant-free survival and eventual Fontan candidacy are similar between groups. Delaying surgical palliation with the CompSt2 did not mitigate the impact of early risk factors such as low birth weight and aortic atresia. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Serum insulin-like growth factor-1 levels in females and males in different cervical vertebral maturation stages

Directory of Open Access Journals (Sweden)

Shreya Gupta

2015-04-01

Full Text Available OBJECTIVE: The aim of this cross sectional study was to assess serum insulin-like growth factor-1 (IGF-1 levels in female and male subjects at various cervical vertebral maturation (CVM stages. MATERIAL AND METHODS: The study sample consisted of 60 subjects, 30 females and 30 males, in the age range of 8-23 years. For all subjects, serum IGF-1 level was estimated from blood samples by means of chemiluminescence immunoassay (CLIA. CVM was assessed on lateral cephalograms using the method described by Baccetti. Serum IGF-1 level and cervical staging data of 30 female subjects were included and taken from records of a previous study. Data were analyzed by Kruska-Wallis and Mann Whitney test. Bonferroni correction was carried out and alpha value was set at 0.003. RESULTS: Peak value of serum IGF-1 was observed in cervical stages CS3 in females and CS4 in males. Differences between males and females were observed in mean values of IGF-1 at stages CS3, 4 and 5. The highest mean IGF-1 levels in males was observed in CS4 followed by CS5 and third highest in CS3; whereas in females the highest mean IGF-1 levelswas observed in CS3 followed by CS4 and third highest in CS5. Trends of IGF-1 in relation to the cervical stages also differed between males and females. The greatest mean serum IGF-1 value for both sexes was comparable, for females (397 ng/ml values were slightly higher than in males (394.8 ng/ml. CONCLUSIONS: Males and females showed differences in IGF-1 trends and levels at different cervical stages.

Effect of 2,4-dihydroxybenzophenone (BP1) on early life-stage development of the marine copepod Acartia tonsa at different temperatures and salinities

DEFF Research Database (Denmark)

Kusk, Kresten Ole; Avdolli, Manola; Wollenberger, Leah

2011-01-01

a copepodite stage (DT(½) ) at the different conditions were calculated. The DT(½) values decreased from 296 h at 15°C to 89 h at 25°C and were also affected by salinity (126 h at 15‰ and 167 h at 30‰), whereas the light:dark regime and culture density influenced development only to a minor extent. BP1......Benzophenone (BP)-type ultraviolet (UV) filters are widely used in cosmetic and sunscreen products and can enter the aquatic environment. Therefore, we investigated the subchronic toxicity of 2,4-dihydroxybenzophenone (BP1) on the marine calanoid copepod Acartia tonsa in an early life......-stage development study. Since developmental endpoints depend on environmental conditions, a preceding study of A. tonsa development was performed at three temperatures, four salinities, four light:dark regimes, six food densities, and four culture densities. Times elapsed until 50% of the population had reached...

Incidence of WHO stage 3 and 4 conditions following initiation of anti-retroviral therapy in resource limited settings.

Directory of Open Access Journals (Sweden)

Andrea J Curtis

Full Text Available OBJECTIVES: To determine the incidence of WHO clinical stage 3 and 4 conditions during early anti-retroviral therapy (ART in resource limited settings (RLS. DESIGN/SETTING: A descriptive analysis of routine program data collected prospectively from 25 Médecins Sans Frontières supported HIV treatment programs in eight countries between 2002 and 2010. SUBJECTS/PARTICIPANTS: 35,349 study participants with median follow-up on ART of 1.33 years (IQR 0.51-2.41. OUTCOME MEASURES: Incidence in 100 person-years of WHO stage 3 or 4 conditions during 5 periods after ART initiation. Diagnoses of conditions were made according to WHO criteria and relied upon clinical assessments supported by basic laboratory investigations. RESULTS: The incidence of any WHO clinical stage 3 or 4 condition over 3 years was 40.02 per 100 person-years (31.77 for stage 3 and 8.25 for stage 4. The incidence of stage 3 and 4 conditions fell by over 97% between months 0-3 and months 25-36 (77.81 to 2.40 for stage 3 and 28.70 to 0.64 for stage 4. During months 0-3 pulmonary tuberculosis was the most common condition diagnosed in adults (incidence 22.24 per 100 person-years and children aged 5-14 years (25.76 and oral candidiasis was the most common in children <5 years (25.79. Overall incidences were higher in Africa compared with Asia (43.98 versus 12.97 for stage 3 and 8.98 versus 7.05 for stage 4 conditions, p<0.001. Pulmonary tuberculosis, weight loss, oral and oesophageal candidiasis, chronic diarrhoea, HIV wasting syndrome and severe bacterial infections were more common in Africa. Extra-pulmonary tuberculosis, non-tuberculous mycobacterial infection, cryptococcosis, penicilliosis and toxoplasmosis were more common in Asia. CONCLUSIONS: The incidence of WHO stage 3 and 4 conditions during the early period after ART initiation in RLS is high, but greatly reduces over time. This is likely due to both the benefits of ART and deaths of the sickest patients occurring shortly

Variações ontogênicas e sazonais na dieta de Etropus crossotus Jordan e Gilbert, 1882 (Paralichthydae na baía de Ubatuba-Enseada, Estado de Santa Catarina, Brasil = Ontogenetic and seasons changes in the diet of Etropus crossotus Jordan and Gilbert, 1882 (Paralichthydae at Ubatuba-Enseada Bay, Santa Catarina State, Brazil

Directory of Open Access Journals (Sweden)

Matheus Oliveira Freitas

2011-04-01

Full Text Available Foram investigadas as variações ontogênicas e sazonais na dieta de Etropus crossotus coletados na baía de Ubatuba-Enseada, Estado de Santa Catarina, Brasil. Redes de arrasto com porta foram utilizadas para as coletas mensais, e 60 exemplares foram coletados entre outubro de 2003 e setembro de 2004. Maior similaridade entre os Índices de Importância Alimentar foi observada entre a primavera e o outono. Crustáceos decápodes representaram 50% dos itens alimentares durante a primavera e outono, e crustáceos anfípodes foram os itens mais representativos no inverno. Maior similaridade entre os IAifoi observada entre as classes 1, 2 e 4, pela alta representatividade de Decapoda, e entre as classes 5, 6 e 7, em função da representatividade de Decapoda e Amphipoda. Os resultados obtidos foram similares a outros estudos realizados na região costeira Sul do Brasil.Ontogenetic and seasonal changes in the diet of Etropus crossotussampled at Ubatuba-Enseada Bay in Santa Catarina State, Brazil were investigated. A trawl net was used for the surveys, and 60 fish were collected monthly during October (2003 and September (2004. The highest similarity of the Alimentary Importance Index (AII wasobserved between spring and autumn. Crustacea Decapoda represented 50% of the feeding items during spring and fall, and Crustacea Amphipoda were the most representative item in winter. The highest AII similarity was observed among length classes 1, 2 and 4, whichwas related to Decapoda representation, and among length classes 5, 6 and 7, because of Decapoda and Amphipoda importance. Results were similar to other studies in the southern coast of Brazil.

Semen CD4+ T Cells and Macrophages Are Productively Infected at All Stages of SIV infection in Macaques

Science.gov (United States)

Bernard-Stoecklin, Sibylle; Gommet, Céline; Corneau, Aurélien B.; Guenounou, Sabrina; Torres, Claire; Dejucq-Rainsford, Nathalie; Cosma, Antonio; Dereuddre-Bosquet, Nathalie; Le Grand, Roger

2013-01-01

The mucosal events of HIV transmission have been extensively studied, but the role of infected cells present in the genital and rectal secretions, and in the semen, in particular, remains a matter of debate. As a prerequisite to a thorough in vivo investigation of the early transmission events through infected cells, we characterized in detail by multi-parameter flow cytometry the changes in macaque seminal leukocytes during SIVmac251 infection, focusing on T cells, macrophages and dendritic cells. Using immunocytofluorescence targeting SIV proteins and real-time quantitative PCR targeting SIV DNA, we investigated the nature of the infected cells on sorted semen leukocytes from macaques at different stages of infection. Finally, we cocultured semen CD4+ T cells and macrophages with a cell line permissive to SIV infection to assess their infectivity in vitro. We found that primary infection induced strong local inflammation, which was associated with an increase in the number of leukocytes in semen, both factors having the potential to favor cell-associated virus transmission. Semen CD4+ T cells and macrophages were productively infected at all stages of infection and were infectious in vitro. Lymphocytes had a mucosal phenotype and expressed activation (CD69 & HLA-DR) and migration (CCR5, CXCR4, LFA-1) markers. CD69 expression was increased in semen T cells by SIV infection, at all stages of infection. Macrophages predominated at all stages and expressed CD4, CCR5, MAC-1 and LFA-1. Altogether, we demonstrated that semen contains the two major SIV-target cells (CD4+ T cells and macrophages). Both cell types can be productively infected at all stages of SIV infection and are endowed with markers that may facilitate transmission of infection during sexual exposure. PMID:24348253

Simulation and analysis of multi-stage centrifugal fractional extraction process of 4-nitrobenzene glycine enantiomers☆

Institute of Scientific and Technical Information of China (English)

Ping Wen; Kewen Tang; Jicheng Zhou; Panliang Zhang

2015-01-01

Based on the interfacial ligand exchange model and the law of conservation of mass, the multi-stage enantioselective liquid–liquid extraction model has been established to analyze and discuss on multi-stage centrifugal fractional extraction process of 4-nitrobenzene glycine (PGL) enantiomers. The influence of phase ratio, extractant concentra-tion, and PF6−concentration on the concentrations of enantiomers in the extract and raffinate was investigated by experiment and simulation. A good agreement between model and experiment was obtained. On this basis, the influence of many parameters such as location of stage, concentration levels, extractant excess, and number of stages on the symmetric separation performance was simulated. The optimal location of feed stage is the middle of fractional extraction equipment. The feed flow must satisfy a restricted relationship on flow ratios and the liquid throughout of centrifugal device. For desired purity specification, the required flow ratios decrease with extractant concentration and increase with PF6−concentration. When the number of stages is 18 stages at extractant excess of 1.0 or 14 stages at extractant excess of 2.0, the eeeq (equal enantiomeric excess) can reach to 99%.

Validation of World Health Organisation HIV/AIDS clinical staging in predicting initiation of antiretroviral therapy and clinical predictors of low CD4 cell count in Uganda.

Directory of Open Access Journals (Sweden)

Steven Baveewo

Full Text Available INTRODUCTION: The WHO clinical guidelines for HIV/AIDS are widely used in resource limited settings to represent the gold standard of CD4 counts for antiviral therapy initiation. The utility of the WHO-defined stage 1 and 2 clinical factors used in WHO HIV/AIDS clinical staging in predicting low CD4 cell count has not been established in Uganda. Although the WHO staging has shown low sensitivity for predicting CD4<200 cells/mm(3, it has not been evaluated at for CD4 cut-offs of <250 cells/mm(3 or <350 cells/mm(3. OBJECTIVE: To validate the World Health Organisation HIV/AIDS clinical staging in predicting initiation of antiretroviral therapy in a low-resource setting and to determine the clinical predictors of low CD4 cell count in Uganda. RESULTS: Data was collected on 395 participants from the Joint Clinical Research Centre, of whom 242 (61.3% were classified as in stages 1 and 2 and 262 (68% were females. Participants had a mean age of 36.8 years (SD 8.5. We found a significant inverse correlation between the CD4 lymphocyte count and WHO clinical stages. The sensitivity the WHO clinical staging at CD4 cell count of 250 cells/mm(3 and 350 cells/mm(3 was 53.5% and 49.1% respectively. Angular cheilitis, papular pruritic eruptions and recurrent upper respiratory tract infections were found to be significant predictors of low CD4 cell count among participants in WHO stage 1 and 2. CONCLUSION: The WHO HIV/AIDS clinical staging guidelines have a low sensitivity and about half of the participants in stages 1 and 2 would be eligible for ART initiation if they had been tested for CD4 count. Angular cheilitis and papular pruritic eruptions and recurrent upper respiratory tract infections may be used, in addition to the WHO staging, to improve sensitivity in the interim, as access to CD4 machines increases in Uganda.

Efficacy of intravitreal injection of anti-vascular endothelial growth factor agents for stage 4 retinopathy of prematurity.

Science.gov (United States)

Cheng, Hui-Chen; Lee, Shui-Mei; Hsieh, Yi-Ting; Lin, Po-Kang

2015-04-01

To investigate the efficacy of intravitreal injection of anti-vascular endothelial growth factor agents for Stage 4 retinopathy of prematurity. Retrospective case series study. The medical records of patients receiving intravitreal injection of anti-vascular endothelial growth factor agents for Stage 4 retinopathy of prematurity from January 2007 to May 2012 in Taipei Veterans General Hospital were reviewed. A total of 13 eyes of 7 patients (3 boys and 4 girls) with Stage 4 retinopathy of prematurity were included. The mean gestational age and birth weight were 27.6 ± 2.6 weeks (range, 24.5-30.5 weeks) and 893.1 ± 293.2 g (range, 550-1422 g), respectively. The mean age at the time of injection was 38.2 ± 1.9 weeks (range, 36.0-41.5 weeks) postmenstrual age, and the mean follow-up period was 37.8 ± 19.5 months (range, 11.0-67.5 months). The active neovascularization regressed rapidly, and the anatomical outcomes were favorable in all patients. One eye developed recurrent retinal hemorrhage with localized retinal detachment 21 weeks after initial treatment, which resolved after a second injection. There were no ocular or systemic complications in these patients. Intravitreal injection of anti-vascular endothelial growth factor agents may be effective as monotherapy or as supplement to failed laser treatment for patients with Stage 4 retinopathy of prematurity without additional surgical intervention. Further randomized controlled trials are necessary to compare the clinical efficacy and safety with other conventional interventions.

Fucoxanthin exerts differing effects on 3T3-L1 cells according to differentiation stage and inhibits glucose uptake in mature adipocytes

International Nuclear Information System (INIS)

Kang, Seong-Il; Ko, Hee-Chul; Shin, Hye-Sun; Kim, Hyo-Min; Hong, Youn-Suk; Lee, Nam-Ho; Kim, Se-Jae

2011-01-01

Highlights: → Fucoxanthin enhances 3T3-L1 adipocyte differentiation at an early stage. → Fucoxanthin inhibits 3T3-L1 adipocyte differentiation at intermediate and late stages. → Fucoxanthin attenuates glucose uptake by inhibiting the phosphorylation of IRS in mature 3T3-L1 adipocytes. → Fucoxanthin exerts its anti-obesity effect by inhibiting the differentiation of adipocytes at both intermediate and late stages, as well as glucose uptake in mature adipocytes. -- Abstract: Progression of 3T3-L1 preadipocyte differentiation is divided into early (days 0-2, D0-D2), intermediate (days 2-4, D2-D4), and late stages (day 4 onwards, D4-). In this study, we investigated the effects of fucoxanthin, isolated from the edible brown seaweed Petalonia binghamiae, on adipogenesis during the three differentiation stages of 3T3-L1 preadipocytes. When fucoxanthin was applied during the early stage of differentiation (D0-D2), it promoted 3T3-L1 adipocyte differentiation, as evidenced by increased triglyceride accumulation. At the molecular level, fucoxanthin increased protein expression of peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), sterol regulatory element-binding protein 1c (SREBP1c), and aP2, and adiponectin mRNA expression, in a dose-dependent manner. However, it reduced the expression of PPARγ, C/EBPα, and SREBP1c during the intermediate (D2-D4) and late stages (D4-D7) of differentiation. It also inhibited the uptake of glucose in mature 3T3-L1 adipocytes by reducing the phosphorylation of insulin receptor substrate 1 (IRS-1). These results suggest that fucoxanthin exerts differing effects on 3T3-L1 cells of different differentiation stages and inhibits glucose uptake in mature adipocytes.

Novel clinical staging for patients with end-stage gastrointestinal carcinoma.

Science.gov (United States)

Yasuda, Naokuni; Nakashima, Osamu; Ohnaka, Toru; Kamisaka, Koji; Tsunoda, Akira; Kusano, Mitsuo

2006-01-01

We created a new clinical staging system for end-stage gastrointestinal (GI) carcinoma to clarify the therapeutic goals for these patients. Data were obtained from a retrospective review of medical charts. Based on daily clinical observation of 144 patients with end-stage GI carcinoma, we classified the terminal stages as A, B, C, and D. The mean durations of terminal stages A, B, C, and D were 19, 16.6, 6.6, and 1.8 days, respectively, in patients with end-stage gastric cancer and 28.5, 9.1, 5.4, and 1.9 days, respectively, in patients with colorectal cancer. Moreover, 88.0% of patients with gastric carcinoma and 82.6% of patients with colorectal carcinoma passed through terminal stages A, B, C, and D sequentially. The patients in terminal stage B experienced temporary relief of symptoms, but those in terminal stage C did not (P terminal stages can easily be judged by clinical observation and may be an effective new tool with which to manage patients with end-stage GI carcinoma and their families.

Antimalarial agents against both sexual and asexual parasites stages: structure-activity relationships and biological studies of the Malaria Box compound 1-[5-(4-bromo-2-chlorophenyl)furan-2-yl]-N-[(piperidin-4-yl)methyl]methanamine (MMV019918) and analogues.

Science.gov (United States)

Vallone, Alessandra; D'Alessandro, Sarah; Brogi, Simone; Brindisi, Margherita; Chemi, Giulia; Alfano, Gloria; Lamponi, Stefania; Lee, Soon Goo; Jez, Joseph M; Koolen, Karin J M; Dechering, Koen J; Saponara, Simona; Fusi, Fabio; Gorelli, Beatrice; Taramelli, Donatella; Parapini, Silvia; Caldelari, Reto; Campiani, Giuseppe; Gemma, Sandra; Butini, Stefania

2018-04-25

Therapies addressing multiple stages of Plasmodium falciparum life cycle are highly desirable for implementing malaria elimination strategies. MMV019918 (1, 1-[5-(4-bromo-2-chlorophenyl)furan-2-yl]-N-[(piperidin-4-yl)methyl]methanamine) was selected from the MMV Malaria Box for its dual activity against both asexual stages and gametocytes. In-depth structure-activity relationship studies and cytotoxicity evaluation led to the selection of 25 for further biological investigation. The potential transmission blocking activity of 25 versus P. falciparum was confirmed through the standard membrane-feeding assay. Both 1 and 25 significantly prolonged atrioventricular conduction time in Langendorff-isolated rat hearts, and showed inhibitory activity of Ba 2+ current through Ca v 1.2 channels. An in silico target-fishing study suggested the enzyme phosphoethanolamine methyltransferase (PfPMT) as a potential target. However, compound activity against PfPMT did not track with the antiplasmodial activity, suggesting the latter activity relies on a different molecular target. Nevertheless, 25 showed interesting activity against PfPMT, which could be an important starting point for the identification of more potent inhibitors active against both sexual and asexual stages of the parasite. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Alternative pathway for the development of Vα14+ NKT cells directly from CD4-CD8- thymocytes that bypasses the CD4+CD8+ stage.

Science.gov (United States)

Dashtsoodol, Nyambayar; Shigeura, Tomokuni; Aihara, Minako; Ozawa, Ritsuko; Kojo, Satoshi; Harada, Michishige; Endo, Takaho A; Watanabe, Takashi; Ohara, Osamu; Taniguchi, Masaru

2017-03-01

Although invariant V α 14 + natural killer T cells (NKT cells) are thought to be generated from CD4 + CD8 + double-positive (DP) thymocytes, the developmental origin of CD4 - CD8 - double-negative (DN) NKT cells still remains unresolved. Here we provide definitive genetic evidence obtained, through studies of mice with DP-stage-specific ablation of expression of the gene encoding the recombinase component RAG-2 (Rag2) and by a fate-mapping approach, that supports the proposal of the existence of an alternative developmental pathway through which a fraction of DN NKT cells with strong T-helper-type-1 (T H 1)-biased and cytotoxic characteristics develop from late DN-stage thymocytes, bypassing the DP stage. These findings provide new insight into understanding of the development of NKT cells and propose a role for timing of expression of the invariant T cell antigen receptor in determining the functional properties of NKT cells.

CHEMVAL project: report on stages 3 and 4

International Nuclear Information System (INIS)

Read, D.

1991-01-01

This report describes the results of CHEMVAL Stages 3 and 4, an international coupled chemical transport model verification/validation exercise involving the participation of research organisations within EC countries, Sweden, Switzerland and Finland. The methodology employed and results obtained for fifteen verification tests of varying complexity are described. The outcome of validation studies against two well characterised experimental systems is also assessed in terms of the requirements for radiological risk assessment. (author)

Experiments of 4-stage pulse power system for rock fragmentation

International Nuclear Information System (INIS)

Chung Kyoung-Jae; Kim Chul-Yeong; Chang Cheol-Jong; Jeong Soon-Hyoung

2002-01-01

The blasting method using the high current electrical discharge has been verified as a green technology against such environmental pollutions as blasting vibration, noise and the scattering of broken pieces of rock. In fact, EPIT TM (Electro-Power Impact Technology) has been applied to dozens of construction sites in Korea, and it has been evaluated as a competitive blasting technique compared with other rock breaking methods. For more effective blasting, however, the sequential blasting technique, sEPIT TM (Sequential Electro-Power Impact Technology) has been developed since September, 2001. The prototype equipment for 4-stage pulse generation was made and has been tested. The equipment consists of a capacitor charging power supply, a capacitor bank, solid-state switches and high voltage relays. The delay time between stages can be controlled in milliseconds by programmable logic controller. The dummy load tests for the 4-stage high current discharge have been performed successfully in the laboratory. The error level is below 8% of preset delay time, and it is allowable for this application. Now, authors are investigating to find out the optimum time delays depending on rock strength. Detailed characteristics of the equipment and some test results are described in this paper

Therapeutic PD-L1 and LAG-3 blockade rapidly clears established blood-stage Plasmodium infection

Science.gov (United States)

Butler, Noah S.; Moebius, Jacqueline; Pewe, Lecia L.; Traore, Boubacar; Doumbo, Ogobara K.; Tygrett, Lorraine T.; Waldschmidt, Thomas J.; Crompton, Peter D.; Harty, John T.

2011-01-01

Plasmodium infection of erythrocytes induces clinical malaria. Parasite-specific CD4+ T cells correlate with reduced parasite burdens and severity of human malaria, and are required to control blood-stage infection in mice. However, the characteristics of CD4+ T cells that determine protection or parasite persistence remain unknown. Here we show that P. falciparum infection of humans increased expression of an inhibitory receptor (PD-1) associated with T cell dysfunction. In vivo blockade of PD-L1 and LAG-3 restored CD4+ T cell function, amplified T follicular helper cell and germinal center B cell and plasmablast numbers, enhanced protective antibodies and rapidly cleared blood-stage malaria in mice. Thus, chronic malaria drives specific T cell dysfunction, which can be rescued to enhance parasite control using inhibitory therapies. PMID:22157630

Three Stage Maturity Model in SME’s towards Industry 4.0

OpenAIRE

Ganzarain, Jaione; Errasti, Nekane

2016-01-01

Purpose: To address the challenges regarding the concept of Industry 4.0 and the diversification methodology and based on the strategic guidance towards Industry 4.0, we propose a process model as a guiding framework for Industry 4.0 collaborative diversification vision, strategy and action building. In this paper we suggest a stage process model to guide and train companies to identify new opportunities for diversification within Industry 4.0. Systematically carrying out the s...

Lipid Peroxidation and Transforming Growth Factor-β1 Levels in Gastric Cancer at Pathologic Stages.

Science.gov (United States)

Tüzün, Sefa; Yücel, Ahmet Fikret; Pergel, Ahmet; Kemik, Ahu Sarbay; Kemik, Ozgür

2012-09-01

High levels of TGF-β1 and enhanced TGF-β1 receptor signaling are related to the pathology of gastric cancer. This effect is caused by oxidative stress and lipid peroxidation products. The aim of this study was to investigate the levels of TGF-β1 and lipid peroxidation products in gastric cancer patients and their correlation with pathologic stage. Lipid peroxidation products and TGF-β1 levels were studied in the serum samples of 50 gastric cancer patients and 18 control subjects. HNE-protein adducts and TGF-β1 levels were significantly higher in T2, T3 and T4 gastric cancers than in either the T1 stage or controls (p<0.001). Pathologic stage was correlated with TGF-β1 levels (r=0.702, p<0.05). These markers production may contribute to tumor angiogenesis and aid in the prognosis of the gastric cancer.

Sites of extranodal involvement are prognostic in patients with stage 1 follicular lymphoma

OpenAIRE

Shastri, Aditi; Janakiram, Murali; Mantzaris, Ioannis; Yu, Yiting; Londono, Jaime S.; Verma, Amit K.; Barta, Stefan K.

2017-01-01

Objectives Follicular lymphoma (FL) is the most common indolent B cell lymphoma in the United States and a quarter of patients present with stage I disease. The objective of this study was to examine if primary site of disease influences survival in early stage lymphoma. Results The most common extranodal primary sites were the integumentary system (8%), followed by the GI tract (6.4%) and head & neck (5.6%). We stratified patients into a pre-rituximab era (1983-1998) and the rituximab era (1...

Role of pelvic lymphadenectomy in stage 1A endometrial carcinoma ...

African Journals Online (AJOL)

Hossam Hassan Aly Hassan El Sokkary

2013-10-31

Oct 31, 2013 ... phadenectomy in managing stage 1A diagnosed preoperatively, we try to evaluate this need. Objective: To ... Methods: 60 Cases of endometrial carcinoma diagnosed by fractional curettage and proved to be stage 1A .... The strongest argument for routine staging is the avoidance of pelvic radiation therapy ...

Silencing of Kv4.1 potassium channels inhibits cell proliferation of tumorigenic human mammary epithelial cells

International Nuclear Information System (INIS)

Jang, Soo Hwa; Choi, Changsun; Hong, Seong-Geun; Yarishkin, Oleg V.; Bae, Young Min; Kim, Jae Gon; O'Grady, Scott M.; Yoon, Kyong-Ah; Kang, Kyung-Sun; Ryu, Pan Dong; Lee, So Yeong

2009-01-01

Potassium channel activity has been shown to facilitate cell proliferation in cancer cells. In the present study, the role of Kv4.1 channels in immortal and tumorigenic human mammary epithelial cells was investigated. Kv4.1 protein expression was positively correlated with tumorigenicity. Moreover, transfection with siRNAs targeting Kv4.1 mRNA suppressed proliferation of tumorigenic mammary epithelial cells. Experiments using mRNA isolated from human breast cancer tissues revealed that the level of Kv4.1 mRNA expression varied depending on the stage of the tumor. Kv4.1 protein expression increased during stages T2 and T3 compared to normal tissue. These results demonstrated that Kv4.1 plays a role in proliferation of tumorigenic human mammary epithelial cells. In addition, elevated Kv4.1 expression may be useful as a diagnostic marker for staging mammary tumors and selective blockers of Kv4.1 may serve to suppress tumor cell proliferation.

Evaluation of insulin like growth factor-1 (If-1) in children with different stages of chronicle renal failure

International Nuclear Information System (INIS)

Derakshan, A.; Karamifar, H.; Razavi, N.S.M.; Fallahzadeh, M.H.; Hashemi, G.H.

2007-01-01

Growth retardation in children with chronic kidney disease (CKD) is multifactorial that include inadequate protein and calorie intake, persistent metabolic acidosis, calcitriol deficiency, renal osteodystrophy, drug toxicity, uremic toxins and growth factor abnormalities such as insulin- like growth factor (IGF) and IGF binding proteins. In this study, we compare the IGF-1 levels in normal and growth retarded CKD children. Serum IGF-1 levels were determined in 22 children with end-stage renal disease, 26 children, with CKD at different stages, 23 children with normal height and weight for age, and 23 children with constitutionally short stature. Mean serum levels of IGF-1 were 209+- ng/m1 in the ESRD group (group1), 159+-163 ng/m1 in the CKD group (group2), 420+-182 ng/ml in normal children (group3), and 360+-183 ng/ml in children with constitutional short stature (group4). The differences in the levels of IGF-1 in groups 1 and 2 were statistically significant when compared to groups 3 and 4(p<0.0001 and p< 0.02, respectively), while the levels of IGF-1 were not statistically different between groups 1 and 2. No correlation was found between IGF-1levels and glomerular filtrations are height or weight in groups 1 and 2. In conclusion, serum levels of IGF-1 in children with CKD are significantly lower than healthy children. (author)

Lipid Peroxidation and Transforming Growth Factor-β1 Levels in Gastric Cancer at Pathologic Stages

Directory of Open Access Journals (Sweden)

Özgür Kemik

2012-09-01

Full Text Available Objective: High levels of TGF-β1 and enhanced TGF-β1 receptor signaling are related to the pathology of gastric cancer. This effect is caused by oxidative stress and lipid peroxidation products. The aim of this study was to investigate the levels of TGF-β1 and lipid peroxidation products in gastric cancer patients and their correlation with pathologic stage. Material and Methods: Lipid peroxidation products and TGF-β1 levels were studied in the serum samples of 50 gastric cancer patients and 18 control subjects.Results: HNE-protein adducts and TGF-β1 levels were significantly higher in T2, T3 and T4 gastric cancers than in either the T1 stage or controls (p<0.001. Pathologic stage was correlated with TGF-β1 levels (r=0.702, p<0.05.Conclusion: These markers production may contribute to tumor angiogenesis and aid in the prognosis of the gastric cancer.

Synthetic TLR4 agonists enhance functional antibodies and CD4+ T-cell responses against the Plasmodium falciparum GMZ2.6C multi-stage vaccine antigen

DEFF Research Database (Denmark)

Baldwin, Susan L; Roeffen, Will; Singh, Susheel K

2016-01-01

A subunit vaccine targeting both transmission and pathogenic asexual blood stages of Plasmodium falciparum, i.e., a multi-stage vaccine, could be a powerful tool to combat malaria. Here, we report production and characterization of the recombinant protein GMZ2.6C, which contains a fragment of the......-γ and TNF in response to GMZ2.6C. Both of these agonists have good safety records in humans....... of the sexual-stage protein Pfs48/45-6C genetically fused to GMZ2, an asexual vaccine antigen in advanced clinical development. To select the most suitable vaccine formulation for downstream clinical studies, GMZ2.6C was tested with various immune modulators in different adjuvant formulations (stable emulsions......, liposomes, and alum) in C57BL/6 mice. Some, but not all, formulations containing either the synthetic TLR4 agonist GLA or SLA elicited the highest parasite-specific antibody titers, the greatest IFN-γ responses in CD4+ TH1 cells, and the highest percentage of multifunctional CD4+ T cells expressing IFN...

Lernpunkt Deutsch--Stage 1.

Science.gov (United States)

Theil, Elvira

1997-01-01

Evaluates the first stage of "Lernpunkt Deutsch," a new three-stage German course designed for upper elementary and early secondary school. Describes the publisher's package of materials and the appropriateness of the course, utility of the different package elements, format of the materials, and assesses whether the course provides pedagogically…

Mechanisms underlying stage-1 TRPL channel translocation in Drosophila photoreceptors.

Directory of Open Access Journals (Sweden)

Minh-Ha Lieu

Full Text Available TRP channels function as key mediators of sensory transduction and other cellular signaling pathways. In Drosophila, TRP and TRPL are the light-activated channels in photoreceptors. While TRP is statically localized in the signaling compartment of the cell (the rhabdomere, TRPL localization is regulated by light. TRPL channels translocate out of the rhabdomere in two distinct stages, returning to the rhabdomere with dark-incubation. Translocation of TRPL channels regulates their availability, and thereby the gain of the signal. Little, however, is known about the mechanisms underlying this trafficking of TRPL channels.We first examine the involvement of de novo protein synthesis in TRPL translocation. We feed flies cycloheximide, verify inhibition of protein synthesis, and test for TRPL translocation in photoreceptors. We find that protein synthesis is not involved in either stage of TRPL translocation out of the rhabdomere, but that re-localization to the rhabdomere from stage-1, but not stage-2, depends on protein synthesis. We also characterize an ex vivo eye preparation that is amenable to biochemical and genetic manipulation. We use this preparation to examine mechanisms of stage-1 TRPL translocation. We find that stage-1 translocation is: induced with ATP depletion, unaltered with perturbation of the actin cytoskeleton or inhibition of endocytosis, and slowed with increased membrane sterol content.Our results indicate that translocation of TRPL out of the rhabdomere is likely due to protein transport, and not degradation/re-synthesis. Re-localization from each stage to the rhabdomere likely involves different strategies. Since TRPL channels can translocate to stage-1 in the absence of ATP, with no major requirement of the cytoskeleton, we suggest that stage-1 translocation involves simple diffusion through the apical membrane, which may be regulated by release of a light-dependent anchor in the rhabdomere.

Late-stage galaxy mergers in cosmos to z ∼ 1

International Nuclear Information System (INIS)

Lackner, C. N.; Silverman, J. D.; Salvato, M.; Kampczyk, P.; Kartaltepe, J. S.; Sanders, D.; Lee, N.; Capak, P.; Scoville, N.; Civano, F.; Halliday, C.; Ilbert, O.; Le Fèvre, O.; Jahnke, K.; Koekemoer, A. M.; Liu, C. T.; Sheth, K.; Toft, S.

2014-01-01

The role of major mergers in galaxy and black hole formation is not well-constrained. To help address this, we develop an automated method to identify late-stage galaxy mergers before coalescence of the galactic cores. The resulting sample of mergers is distinct from those obtained using pair-finding and morphological indicators. Our method relies on median-filtering of high-resolution images to distinguish two concentrated galaxy nuclei at small separations. This method does not rely on low surface brightness features to identify mergers, and is therefore reliable to high redshift. Using mock images, we derive statistical contamination and incompleteness corrections for the fraction of late-stage mergers. The mock images show that our method returns an uncontaminated (<10%) sample of mergers with projected separations between 2.2 and 8 kpc out to z∼1. We apply our new method to a magnitude-limited (m FW 814 <23) sample of 44,164 galaxies from the COSMOS HST/ACS catalog. Using a mass-complete sample with logM ∗ /M ⊙ >10.6 and 0.251.00, we find ∼5% of systems are late-stage mergers. Correcting for incompleteness and contamination, the fractional merger rate increases strongly with redshift as r merge ∝(1+z) 3.8±0.9 , in agreement both with earlier studies and with dark matter halo merger rates. Separating the sample into star-forming and quiescent galaxies shows that the merger rate for star-forming galaxies increases strongly with redshift, (1+z) 4.5±1.3 , while the merger rate for quiescent galaxies is consistent with no evolution, (1+z) 1.1±1.2 . The merger rate also becomes steeper with decreasing stellar mass. Limiting our sample to galaxies with spectroscopic redshifts from zCOSMOS, we find that the star formation rates and X-ray selected active galactic nucleus (AGN) activity in likely late-stage mergers are higher by factors of ∼2 relative to those of a control sample. Combining our sample with more widely separated pairs, we find that 8�

Vaginal cancer, an analysis of stages 1 and 2

International Nuclear Information System (INIS)

Dickie, G.J.; Tripcony, L.; Otten, G.; Nicklin, J.

2003-01-01

A retrospective analysis was performed of 70 patients with stages 1 and 2 vaginal cancer seen between 1982 and 1998 at the Royal Brisbane and Royal Women's Hospitals, Queensland. Forty three patients had previously had a hysterectomy. Stage, histology and grade were the most important prognostic factors. The 5 year survival rate for stage 1 was 71%, compared to 48% for stage 2. The majority (61 patients) had squamous cell carcinoma with a 68% survival compared to 22% for adenocarcinoma. Those with histological grade 1 and 2 had a 69% survival compared to 40% for grade 3 disease. Age, whether the patient had a previous hysterectomy, tumour site and size were not significant prognostic factors. The majority of patients were treated with radiotherapy alone. However those that had surgery alone or surgery combined with radiotherapy had a significantly improved survival compared to the radiotherapy alone group. The majority of tumours recurred in the loco-regional area and the median time to recurrence was 12 months

A Comparison of Treating Metabolic Acidosis in CKD Stage 4 Hypertensive Kidney Disease with Fruits and Vegetables or Sodium Bicarbonate

Science.gov (United States)

Goraya, Nimrit; Simoni, Jan; Jo, Chan-Hee

2013-01-01

Summary Background and objectives Current guidelines recommend Na+-based alkali for CKD with metabolic acidosis and plasma total CO2 (PTCO2) fruits and vegetables with oral NaHCO3 (HCO3) regarding the primary outcome of follow-up estimated GFR (eGFR) and secondary outcomes of improved metabolic acidosis and reduced urine indices of kidney injury. Design, setting, participants, & measurements Individuals with stage 4 (eGFR, 15–29 ml/min per 1.73 m2) CKD due to hypertensive nephropathy, had a PTCO2 level fruits and vegetables dosed to reduce dietary acid by half (n=36). Results Plasma cystatin C–calculated eGFR did not differ at baseline and 1 year between groups. One-year PTCO2 was higher than baseline in the HCO3 group (21.2±1.3 versus 19.5±1.5 mM; Pfruits and vegetables group (19.9±1.7 versus 19.3±1.9 mM; Pfruits and vegetable group (Pfruits and vegetables or NaHCO3 in individuals with stage 4 CKD yielded eGFR that was not different, was associated with higher-than-baseline PTCO2, and was associated with lower-than-baseline urine indices of kidney injury. The data indicate that fruits and vegetables improve metabolic acidosis and reduce kidney injury in stage 4 CKD without producing hyperkalemia. PMID:23393104

Clinical stage T1c prostate cancer: evaluation with endorectal MR imaging and MR spectroscopic imaging.

Science.gov (United States)

Zhang, Jingbo; Hricak, Hedvig; Shukla-Dave, Amita; Akin, Oguz; Ishill, Nicole M; Carlino, Lauren J; Reuter, Victor E; Eastham, James A

2009-11-01

To assess the diagnostic accuracy of endorectal magnetic resonance (MR) imaging and MR spectroscopic imaging for prediction of the pathologic stage of prostate cancer and the presence of clinically nonimportant disease in patients with clinical stage T1c prostate cancer. The institutional review board approved-and waived the informed patient consent requirement for-this HIPAA-compliant study involving 158 patients (median age, 58 years; age range, 40-76 years) who had clinical stage T1c prostate cancer, had not been treated preoperatively, and underwent combined 1.5-T endorectal MR imaging-MR spectroscopic imaging between January 2003 and March 2004 before undergoing radical prostatectomy. On the MR images and combined endorectal MR-MR spectroscopic images, two radiologists retrospectively and independently rated the likelihood of cancer in 12 prostate regions and the likelihoods of extracapsular extension (ECE), seminal vesicle invasion (SVI), and adjacent organ invasion by using a five-point scale, and they determined the probability of clinically nonimportant prostate cancer by using a four-point scale. Whole-mount step-section pathology maps were used for imaging-pathologic analysis correlation. Receiver operating characteristic curves were constructed and areas under the curves (AUCs) were estimated nonparametrically for assessment of reader accuracy. At surgical-pathologic analysis, one (0.6%) patient had no cancer; 124 (78%) patients, organ-confined (stage pT2) disease; 29 (18%) patients, ECE (stage pT3a); two (1%) patients, SVI (stage pT3b); and two (1%) patients, bladder neck invasion (stage pT4). Forty-six (29%) patients had a total tumor volume of less than 0.5 cm(3). With combined MR imaging-MR spectroscopic imaging, the two readers achieved 80% accuracy in disease staging and AUCs of 0.62 and 0.71 for the prediction of clinically nonimportant cancer. Clinical stage T1c prostate cancers are heterogeneous in pathologic stage and volume. MR imaging may

Three stage maturity model in SME’s toward industry 4.0

Energy Technology Data Exchange (ETDEWEB)

Ganzarain, J.; Errasti, N.

2016-07-01

To address the challenges regarding the concept of Industry 4.0 and the diversification methodology and based on the strategic guidance towards Industry 4.0, we propose a process model as a guiding framework for Industry 4.0 collaborative diversification vision, strategy and action building. In this paper we suggest a stage process model to guide and train companies to identify new opportunities for diversification within Industry 4.0. Systematically carrying out the stages will take a company to their individual specific vision and collaborative vision between different companies in the Industry 4.0 scenario. Design/methodology/approach: This new collaborative diversification methodology involves industry within the pilot program; from the diversification and capacity assessment analysis of the companys profile, skills and technologies that dominates, to identify the diversification opportunity map and its business modeling within the Industry 4.0 paradigm. Findings: The application of maturity models to the Industry 4.0 may help organizations to integrate this methodology into their culture. Results show a real need for guided support in developing a company-specific Industry 4.0 vision and specific project planning. Originality/value: Industry 4.0 promotes a vision where recent developments in information technology are expected to enable entirely new forms of cooperative engineering and manufacturing. The vision of industry 4.0 describes a whole new approach to business operations, and especially the production industries. To address the challenges regarding the concept of Industry 4.0 and the diversification methodology discussed above, and based on the strategic guidance towards Industry 4.0, we propose a unique process model as a guiding framework for Industry 4.0 collaborative diversification vision, strategy and action building.

Three stage maturity model in SME’s toward industry 4.0

International Nuclear Information System (INIS)

Ganzarain, J.; Errasti, N.

2016-01-01

To address the challenges regarding the concept of Industry 4.0 and the diversification methodology and based on the strategic guidance towards Industry 4.0, we propose a process model as a guiding framework for Industry 4.0 collaborative diversification vision, strategy and action building. In this paper we suggest a stage process model to guide and train companies to identify new opportunities for diversification within Industry 4.0. Systematically carrying out the stages will take a company to their individual specific vision and collaborative vision between different companies in the Industry 4.0 scenario. Design/methodology/approach: This new collaborative diversification methodology involves industry within the pilot program; from the diversification and capacity assessment analysis of the companys profile, skills and technologies that dominates, to identify the diversification opportunity map and its business modeling within the Industry 4.0 paradigm. Findings: The application of maturity models to the Industry 4.0 may help organizations to integrate this methodology into their culture. Results show a real need for guided support in developing a company-specific Industry 4.0 vision and specific project planning. Originality/value: Industry 4.0 promotes a vision where recent developments in information technology are expected to enable entirely new forms of cooperative engineering and manufacturing. The vision of industry 4.0 describes a whole new approach to business operations, and especially the production industries. To address the challenges regarding the concept of Industry 4.0 and the diversification methodology discussed above, and based on the strategic guidance towards Industry 4.0, we propose a unique process model as a guiding framework for Industry 4.0 collaborative diversification vision, strategy and action building.

Computed tomography in the staging of esophageal carcinoma

International Nuclear Information System (INIS)

Han, Kyung Min; Lee, Jong Tae; Yoo, Hyung Sik

1986-01-01

Computed Tomography (CT) was found to be highly accurate in predicting tumor size and assessing invasion of the surrounding structures and distant metastasis. Also CT played an important role for determination of operability of esophageal carcinoma. The CT findings with barium esophagogram in 21 patients with histologically proven esophageal carcinoma were reviewed from Feb. 1985 to Feb. 1986 at the department of Radiology, Yonsei University, College of Medicine. The results were as follows: 1. Number of patients in each stages were: 2 in stage 1, 6 in stage 2, 4 in stage 3, and 9 in stage 4. 2. Paek age distribution was in tis 6th decades as 9 patients (42.9%). Overall mean age was 60.8 years. Number of male patients were 19 and 2 of female. 3. Histologic types of esophageal carcinoma were 19 cases of epidermoid (90.5%) and 2 cases of adenocarcinoma (9.5%). 4. The tumor location was 1 case in upper, 14 cases (66.7%) in middle and 6 cases in lower one-third. 5. Various types of esophageal carcinoma were as follows: 3 cases of fungating, 4 cases of infiltrating, 5 cases of ulcerofungating, and 9 cases of ulceroinfiltrating type. 6. Average length of involvement in each stages were 4 cm in stage 1, 5.5 cm in stage 2, 8.8 cm stage 3, and 8.3 cm in stage 4. The involved length was longer in advanced cases. In 11 cases (52.4%), the involved length was between 4 and 8 cm. 7. Angle of periaortic fat plane obliteration of the aortic circumference were as follows: Below 45 (7 cases 33.3%), 45-90 (3 cases 14.3%), over 90 (11 cases, 52.4%). 8. Method of treatment of esophageal carcinoma were as follows: Only radiotherapy in 11 cases (52.4%), radiotherapy with operation in 5 cases, only operation on 1 case, and no treatment in 4 cases. 9. Distant metastatic sites were: brain in 1, pericardium in 5, liver in 5, trachea in 2, bronchus in 9, and distant lymph node in 5 cases.

Low Expression of TBX4 Predicts Poor Prognosis in Patients with Stage II Pancreatic Ductal Adenocarcinoma

Directory of Open Access Journals (Sweden)

Meijuan Zong

2011-08-01

Full Text Available This study was designed to investigate the expression of the T-box transcription factor 4 (TBX4, a tumor biomarker that was previously identified by proteomics, in pancreatic ductal adenocarcinoma (PDAC and evaluate its clinical utility as a potential prognostic biomarkers for PDAC. The expression of TBX4 was detected in 77 stage II PDAC tumors by immunohistochemistry, and the results were analyzed with regard to clinicopathological characteristics and overall survival. Moreover, Tbx4 promoter methylation status in primary PDAC tumors and normal adjacent pancreas tissues was measured by bisulfite sequencing. Among 77 stage II PDAC tumors, 48 cases (62.3% expressed TBX4 at a high level. No significant correlation between TBX4 expression and other clinicopathological parameters, except tumor grade and liver metastasis recurrence, was found. The survival of patients with TBX4-high expression was significantly longer than those with TBX4-low expression (P = 0.010. In multivariate analysis, low TBX4 expression was an independent prognostic factor for overall survival in patients with stage II PDAC. TBX4 promoter methylation status was frequently observed in both PDAC and normal adjacent pancreas. We conclude that a low level of TBX4 expression suggests a worse prognosis for patients with stage II PDAC. Down-regulation of the TBX4 gene in pancreas is less likely to be regulated by DNA methylation.

Cost-effectiveness of Early Treatment of Hepatitis C Virus Genotype 1 by Stage of Liver Fibrosis in a US Treatment-Naive Population

Science.gov (United States)

Chahal, Harinder S.; Marseille, Elliot A.; Tice, Jeffrey A.; Pearson, Steve D.; Ollendorf, Daniel A.; Fox, Rena K.; Kahn, James G.

2016-01-01

IMPORTANCE Novel treatments for hepatitis C virus (HCV) infection are highly efficacious but costly. Thus, many insurers cover therapy only in advanced fibrosis stages. The added health benefits and costs of early treatment are unknown. OBJECTIVE To assess the cost-effectiveness of (1) treating all patients with HCV vs only those with advanced fibrosis and (2) treating each stage of fibrosis. DESIGN, SETTING, AND PARTICIPANTS This study used a decision-analytic model for the treatment of HCV genotype 1. The model used a lifetime horizon and societal perspective and was representative of all US patients with HCV genotype 1 who had not received previous treatment. Comparisons in the model included antiviral treatment of all fibrosis stages (METAVIR [Meta-analysis of Histological Data in Virial Hepatitis] stages F0 [no fibrosis] to F4 [cirrhosis]) vs treatment of stages F3 (numerous septa without cirrhosis) and F4 only and by specific fibrosis stage. Data were collected from March 1 to September 1, 2014, and analyzed from September 1, 2014, to June 30, 2015. INTERVENTIONS Six HCV therapy options (particularly combined sofosbuvir and ledipasvir therapy) or no treatment. MAIN OUTCOMES AND MEASURES Cost and health outcomes were measured using total medical costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs), calculated as the difference in costs between strategies divided by the difference in QALYs. RESULTS We simulated 1000 individuals, but present the results normalized to a single HCV-infected person. In the base-case analysis, among patients receiving 8 or 12 weeks of sofosbuvir-ledipasvir treatment, treating all fibrosis stages compared with treating stages F3 and F4 adds 0.73 QALYs and $28 899, for an ICER of $39 475 per QALY gained. Treating at stage F2 (portal fibrosis with rare septa) costs $19 833 per QALY gained vs waiting until stage F3; treating at stage F1 (portal fibrosis without septa), $81 165 per QALY gained

New clinical staging for pharyngeal surgery in obstructive sleep apnea patients.

Science.gov (United States)

Vidigal, Tatiana Aguiar; Haddad, Fernanda Louise Martinho; Cabral, Rafael Ferreira Pacheco; Oliveira, Maria Claudia Soares; Cavalcante, Ricardo Rodrigues; Bittencourt, Lia Rita Azeredo; Tufik, Sergio; Gregório, Luis Carlos

2014-01-01

The success of pharyngeal surgery in the treatment of obstructive sleep apnea syndrome depends on the appropriate selection of patients. To propose a new staging for indication of pharyngeal surgery in obstructive sleep apnea syndrome. A total of 54 patients undergoing extended tonsillectomy were retrospectively included, divided into six stages. Stage I: patients with palatine tonsils grade 3/4 and modified Mallampati index 1/2; stage II: palatine tonsils 3/4 and modified Mallampati index 3/4; stage III: palatine tonsils 1/2 and modified Mallampati index 1/2; stage IV: palatine tonsils 1/2 and modified Mallampati index 3/4; stage V: body mass index ≥40 kg/m(2) with palatine tonsils 3/4 and modified Mallampati index 1, 2, 3, or 4. Stage VI: body mass index ≥40 with palatine tonsils 1/2 and modified Mallampati index 1, 2, 3, or 4. The surgical success rates were 88.9%, 75.0%, 35.7%, 38.5%, and 100.0% in stages I-V. The presence of hypertrophic palatine tonsils was the anatomical factor in common in the most successful stages (I, II, and V), regardless of body mass index. Although the modified Mallampati index classes 3 and 4 reduced the success rate of surgery in patients with hypertrophic tonsils (stage II), the presence of modified Mallampati index classes 1 and 2 did not favor surgical success in patients with normal tonsils (stage III). Copyright © 2014 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

A loss of profilin-1 in late-stage oral squamous cell carcinoma.

Science.gov (United States)

Adami, Guy R; O'Callaghan, Thomas N; Kolokythas, Antonia; Cabay, Robert J; Zhou, Yalu; Schwartz, Joel L

2017-08-01

The genes for PFN1 and TMSB4 are both highly expressed in oral tissue and both encode actin monomer binding proteins thought to play a role in cell motility and possibly other crucial parts of tumor progression. Oral brush cytology of epithelium from oral squamous cell carcinoma (OSCC) was used to measure PFN1 and TMSB4 mRNA in OSCC, while immunohistochemical analysis of tissue was used to check protein levels. High but variable expression of mRNAs encoding these two proteins was observed suggesting they may contribute to tumor characteristics in a subset of OSCCs. Both proteins were highly expressed in normal appearing basal epithelium, in the cytoplasm, and perinuclear area, while expression was minimal in upper epithelial layers. In OSCCs, expression of these proteins varied. In tumors classified as later stage, based on size and/or lymph node involvement, PFN1 levels were lower in tumor epithelium. A control gene, KRT13, showed expression in normal differentiated basal and suprabasal oral mucosa epithelial cells and as reported was lost in OSCC cells. Loss of PFN1 in tumor cells has been associated with lymph node invasion and metastasis in other tumor types, strengthening the argument that the protein has the potential to be a tumor suppressor in late-stage OSCC. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

CT staging of renal cell carcinoma using the revised 1997 TNM staging criteria: in comparison with the previous one

International Nuclear Information System (INIS)

Sung, Deuk Jae; Kim, Yun Hwan; Chung, Hwan Hoon; Chung, Kyoo Byung; Suh, Won Hyuck

2001-01-01

To assess the accuracy of preoperative CT staging of RCC and to compare the relationship between T stage and the incidence of metastasis on the basis of the old (1992) and the new (1997) UICC and AJCC tumor classification system. In 112 cases of surgically resected RCC, the stagings of preoperative CT scans were determined retrospectively by two radiologists and were compared with the results of pathologic examinations. In 70 cases which had been followed up over three years after surgery, the incidence of metastasis at initial diagnosis and during the follow-up period was assessed. All cases were reconsidered, and using the old and the new TNM classification, the incidence of metastasis was compared. According to the old TNM classification, 5 cases (4%) were staged at T1, 73(65%) at T2, 21(19%) at T3a, 9(8%) at T3b, 0 at T3c, and 4(4%) at T4. Using the new TNM classification, we also staged 54 cases (48%) at T1 and 24(21%) at T2. Overall, using this new classification, CT correctly staged 79% of patients (88/112) overstaged 15%(17/112) and understaged 6%(7/112). CT had a sensitivity of 84% and specificity of 91% in new T1 tumors, 71% and 95%, respectively, in new T2 tumors, 69% and 88% in T3a tumors, 78% and 98% in T3b tumors, and 75% and 99% in T4 tumors. CT had a sensitivity of 44% and a specificity of 99% in old T1 tumors, and 82% and 71%, respectively, in old T2 tumors. The incidence of metastasis in CT-staged (cT) tumors was 0% (0/4) in old cT1, 8% (3/39) in new cT1, 29% (4/14) in new cT2, 67% (6/9) in cT3a, and 75% (6/8) in cT3b. In the staging of T1 tumors, CT is more sensitive when the new TNM classification is used. Even though the cut off point between T1 and T2 tumors had been in creased from 2.5 to 7.0 cm, T1 tumors staged according to the new system did not show a significantly higher incidence of metastasis than those staged according to the old

On the presence of the Mediterranean endemic Microdeutopus sporadhi Myers, 1969 (Crustacea: Amphipoda: Aoridae in the Gulf of Naples (Italy with a review on its distribution and ecology

Directory of Open Access Journals (Sweden)

M. B. SCIPIONE

2013-10-01

Full Text Available The species Microdeutopus sporadhi (Crustacea: Amphipoda: Aoridae, endemic of the Mediterranean Sea, was described by Myers in 1969 on material collected from the Aegean Sea in a sheltered environment with high sedimentation rates. A check on the distribution and ecology of M. sporadhi showed that: — although not mentioned in the checklist of amphipods of the Italian seas, it was already found in the central Tyrrhenian Sea in 1983-84 and in the northern Adriatic Sea in 2002-03; — it was rarely found in the Mediterranean Sea, one of the most studied basins as concerns amphipod fauna; but notwithstanding the few records available, the wide ecological spectrum of this species was pointed out. The present study, conducted off the Island of Ischia (Gulf of Naples, Italy, showed the presence of rich and well established populations through time, but only in a peculiar substratum (artificial collectors and environment (low pH values. The species seems to be able to withstand harsh environmental conditions and probably to conceal itself through a cryptic behaviour, escaping traditional sampling methods. The role of rare or hidden species in bio-assessment should be re-evaluated.

Are prostate carcinoma clinical stages T1C and T2 similar?

Directory of Open Access Journals (Sweden)

Athanase Billis

2006-04-01

Full Text Available PURPOSE: A recent study has found that PSA recurrence rate for clinical T1c tumors is similar to T2 tumors, indicating a need for further refinement of clinical staging system. To test this finding we compared clinicopathologic characteristics and the time to PSA progression following radical retropubic prostatectomy of patients with clinical stage T1c tumors to those with stage T2, T2a or T2b tumors. MATERIALS AND METHODS: From a total of 186 consecutive patients submitted to prostatectomy, 33.52% had clinical stage T1c tumors, 45.45% stage T2a tumors and 21.02% stage T2b tumors. The variables studied were age, preoperative PSA, prostate weight, Gleason score, tumor extent, positive surgical margins, extraprostatic extension (pT3a, seminal vesicle invasion (pT3b, and time to PSA progression. Tumor extent was evaluated by a point-count method. RESULTS: Patients with clinical stage T1c were younger and had the lowest mean preoperative PSA. In the surgical specimen, they had higher frequency of Gleason score < 7 and more organ confined cancer. In 40.54% of the patients with clinical stage T2b tumors, there was extraprostatic extension (pT3a. During the study period, 54 patients (30.68% developed a biochemical progression. Kaplan-Meier product-limit analysis revealed no significant difference in the time to PSA progression between men with clinical stage T1c versus clinical stage T2 (p = 0.7959, T2a (p = 0.6060 or T2b (p = 0.2941 as well as between men with clinical stage T2a versus stage T2b (p = 0.0994. CONCLUSION: Clinicopathological features are not similar considering clinical stage T1c versus clinical stages T2, T2a or T2b.

Spatiotemporal proteomic analyses during pancreas cancer progression identifies serine/threonine stress kinase 4 (STK4) as a novel candidate biomarker for early stage disease.

Science.gov (United States)

Mirus, Justin E; Zhang, Yuzheng; Hollingsworth, Michael A; Solan, Joell L; Lampe, Paul D; Hingorani, Sunil R

2014-12-01

Pancreas cancer, or pancreatic ductal adenocarcinoma, is the deadliest of solid tumors, with a five-year survival rate of pancreas cancer. Mouse models that accurately recapitulate the human condition allow disease tracking from inception to invasion and can therefore be useful for studying early disease stages in which surgical resection is possible. Using a highly faithful mouse model of pancreas cancer in conjunction with a high-density antibody microarray containing ∼2500 antibodies, we interrogated the pancreatic tissue proteome at preinvasive and invasive stages of disease. The goal was to discover early stage tissue markers of pancreas cancer and follow them through histologically defined stages of disease using cohorts of mice lacking overt clinical signs and symptoms and those with end-stage metastatic disease, respectively. A panel of seven up-regulated proteins distinguishing pancreas cancer from normal pancreas was validated, and their levels were assessed in tissues collected at preinvasive, early invasive, and moribund stages of disease. Six of the seven markers also differentiated pancreas cancer from an experimental model of chronic pancreatitis. The levels of serine/threonine stress kinase 4 (STK4) increased between preinvasive and invasive stages, suggesting its potential as a tissue biomarker, and perhaps its involvement in progression from precursor pancreatic intraepithelial neoplasia to pancreatic ductal adenocarcinoma. Immunohistochemistry of STK4 at different stages of disease revealed a dynamic expression pattern further implicating it in early tumorigenic events. Immunohistochemistry of a panel of human pancreas cancers confirmed that STK4 levels were increased in tumor epithelia relative to normal tissue. Overall, this integrated approach yielded several tissue markers that could serve as signatures of disease stage, including early (resectable), and therefore clinically meaningful, stages. © 2014 by The American Society for

Atomic resolution structures of discrete stages on the reaction coordinate of the [Fe4S4] enzyme IspG (GcpE)

KAUST Repository

Quitterer, Felix; Frank, Annika; Wang, Ke; Rao, Guodong; O'Dowd, Bing; Li, Jikun; Guerra, Francisco; Abdel-Azeim, Safwat; Bacher, Adelbert; Eppinger, Jö rg; Oldfield, Eric; Groll, Michael

2015-01-01

IspG is the penultimate enzyme in non-mevalonate biosynthesis of the universal terpene building blocks isopentenyl diphosphate and dimethylallyl diphosphate. Its mechanism of action has been the subject of numerous studies but remained unresolved due to difficulties in identifying distinct reaction intermediates. Using a moderate reducing agent as well as an epoxide substrate analogue, we were now able to trap and crystallographically characterize various stages in the IspG catalyzed conversion of 2-C-methyl-D-erythritol-2,4-cyclo-diphosphate (MEcPP) to (E)-1-hydroxy-2-methylbut-2-enyl-4-diphosphate (HMBPP). In addition, the enzyme’s structure was determined in complex with several inhibitors. These results, combined with recent electron paramagnetic resonance data, allowed us to deduce a detailed and complete IspG catalytic mechanism which describes all stages from initial ring opening to formation of HMBPP via discrete radical and carbanion intermediates. The data presented in this article provide a guide for the design of selective drugs against many pro- and eukaryotic pathogens to which the non-mevalonate pathway is essential for survival and virulence.

Atomic resolution structures of discrete stages on the reaction coordinate of the [Fe4S4] enzyme IspG (GcpE)

KAUST Repository

Quitterer, Felix

2015-04-11

IspG is the penultimate enzyme in non-mevalonate biosynthesis of the universal terpene building blocks isopentenyl diphosphate and dimethylallyl diphosphate. Its mechanism of action has been the subject of numerous studies but remained unresolved due to difficulties in identifying distinct reaction intermediates. Using a moderate reducing agent as well as an epoxide substrate analogue, we were now able to trap and crystallographically characterize various stages in the IspG catalyzed conversion of 2-C-methyl-D-erythritol-2,4-cyclo-diphosphate (MEcPP) to (E)-1-hydroxy-2-methylbut-2-enyl-4-diphosphate (HMBPP). In addition, the enzyme’s structure was determined in complex with several inhibitors. These results, combined with recent electron paramagnetic resonance data, allowed us to deduce a detailed and complete IspG catalytic mechanism which describes all stages from initial ring opening to formation of HMBPP via discrete radical and carbanion intermediates. The data presented in this article provide a guide for the design of selective drugs against many pro- and eukaryotic pathogens to which the non-mevalonate pathway is essential for survival and virulence.

Overexpression of AIB1 in nasopharyngeal carcinomas correlates closely with advanced tumor stage.

Science.gov (United States)

Liu, Meng-Zhong; Xie, Dan; Mai, Shi-Juan; Tong, Zhu-Ting; Shao, Jian-Yong; Fu, Yong-Shui; Xia, Wen-Jie; Kung, Hsian-Fu; Guan, Xin-Yuan; Zeng, Yi-Xin

2008-05-01

AIB1, a candidate oncogene in breast cancer, is commonly amplified and overexpressed in several types of human cancers. In this study, expression and amplification of AIB1 in nasopharyngeal carcinoma (NPC) were studied by immunohistochemical analysis and fluorescence in situ hybridization using tissue microarrays, including 80 specimens of NPC and 20 specimens of nonneoplastic nasopharyngeal mucosa. In this NPC cohort, overexpression and amplification of AIB1 was detected in 36 (51%) of 71 and 3 (7%) of 46 NPCs, respectively. Overexpression of AIB1 was observed more frequently in NPCs in late T stages (T3/T4, 24/35 [69%]) than in earlier stages (T1/T2, 12/36 [33%]; P < .05). In addition, 18 (72%) of 25 NPCs with lymph node metastasis (N1-3) showed overexpression of AIB1; the frequency was significantly higher than that in NPCs without node metastasis (N0, 18/49 [39%]; P < .05). These findings suggest that overexpression of AIB1 in NPCs may be important in the acquisition of an invasive and/or metastatic phenotype.

Gas swelling behaviour at different stages in Li4Ti5O12/LiNi1/3Co1/3Mn1/3O2 pouch cells

Science.gov (United States)

Liu, Wei; Liu, Haohan; Wang, Qian; Zhang, Jian; Xia, Baojia; Min, Guoquan

2017-11-01

Gas swelling behaviour is a major drawback of batteries that are based on Li4Ti5O12 anode materials and hinders their application. In this article, the morphology and electronic structure changes of Li4Ti5O12 electrodes at ageing and cycling stages are investigated using scanning electron microscopy, X-ray absorption near-edge structure and X-ray photoelectron spectroscopy. A simple method that uses an air bag to collect the generated gases was conducted and the gases were then characterised by gas chromatography/mass spectrometry. The results indicate that the charge transformation of Ti ions would aggravate the gas swelling behaviour. The solid electrolyte interphase (SEI) films form on the surface of the Li4Ti5O12 particles and become thicker with increasing charge state. The gas components change significantly during the ageing and cycling, indicating the complexity of the gas swelling mechanism.

Tissue inhibitor of metalloproteinase-4 is elevated in early-stage breast cancers with accelerated progression and poor clinical course.

Science.gov (United States)

Liss, Michaelann; Sreedhar, Nandhini; Keshgegian, Albert; Sauter, Guido; Chernick, Michael R; Prendergast, George C; Wallon, U Margaretha

2009-09-01

An increasing number of breast cancer patients are diagnosed with small, localized, early-stage tumors. These patients are typically thought to have a good prognosis for long-term disease-free survival, but epidemiological studies indicate that up to 30% may have a recurrence within 3 to 5 years of diagnosis. Identifying patients with a high risk of recurrence and/or progression is important because they could be more aggressively treated at diagnosis to improve their chances for disease-free survival. Recent evidence suggests that elevated levels of the matrix metalloproteinase inhibitor, tissue inhibitor of metalloproteinase (TIMP)-4, are associated with malignant progression of ductal carcinoma in situ, a precancerous lesion. To examine the association of TIMP-4 with survival outcomes, we conducted a retrospective immunohistochemical analysis of 314 cases from patients with early-stage disease, defined as tumors smaller than 2 cm and no spread to lymph nodes (tumor-node-metastasis staging: T1N0MX). We found that tumors with elevated levels of TIMP-4 were correlated with a reduced probability of long-term disease-free survival, especially in patients with estrogen receptor-negative tumors. Our findings prompt further evaluation of TIMP-4 as a simple prognostic marker that may help identify patients with early-stage breast cancer who could benefit from more aggressive treatment at diagnosis.

Outcomes of Patients With Revised Stage I Clear Cell Sarcoma of Kidney Treated in National Wilms Tumor Studies 1-5

International Nuclear Information System (INIS)

Kalapurakal, John A.; Perlman, Elizabeth J.; Seibel, Nita L.; Ritchey, Michael; Dome, Jeffrey S.; Grundy, Paul E.

2013-01-01

Purpose: To report the clinical outcomes of children with revised stage I clear cell sarcoma of the kidney (CCSK) using the National Wilms Tumor Study Group (NWTS)-5 staging criteria after multimodality treatment on NWTS 1-5 protocols. Methods and Materials: All CCSK patients enrolled in the National Wilms Tumor Study Group protocols had their pathology slides reviewed, and only those determined to have revised stage I tumors according to the NWTS-5 staging criteria were included in the present analysis. All patients were treated with multimodality therapy according to the NWTS 1-5 protocols. Results: A total of 53 children were identified as having stage I CCSK. All patients underwent primary surgery with radical nephrectomy. The chemotherapy regimens used were as follows: regimen A, C, F, or EE in 4 children (8%); regimen DD or DD4A in 33 children (62%); regimen J in 4 children (8%); and regimen I in 12 children (22%). Forty-six patients (87%) received flank radiation therapy (RT). Seven children (13%) did not receive flank RT. The median delay between surgery and the initiation of RT was 9 days (range, 3-61). The median RT dose was 10.8 Gy (range, 10-36). The flank RT doses were as follows: 10.5 or 10.8 Gy in 25 patients (47%), 11-19.9 Gy in 2 patients (4%), 20-29.9 Gy in 9 patients (17%), and 30-40 Gy in 10 patients (19%). The median follow-up for the entire group was 17 years (range, 2-36). The relapse-free and cancer-specific survival rate was 100% at the last follow-up examination. Conclusions: The present results have demonstrated that children with revised stage I CCSK using the NWTS-5 staging criteria have excellent survival rates despite the use of varying RT doses and chemotherapy regimens in the NWTS 1-5 protocols.

Evaluation of the I. Stage of decommissioning and implementation of the II. Stage of decommissioning of NPP V1

International Nuclear Information System (INIS)

Hrasnova, E.

2015-01-01

In this paper author deals with following aspects: 1. Introduction of company Nuclear and Decommissioning Company, plc; 2. Evaluation of the I. stage of decommissioning and implementation of the II. Stage of decommissioning of NPP V1; (author)

Active form Notch4 promotes the proliferation and differentiation of 3T3-L1 preadipocytes

Energy Technology Data Exchange (ETDEWEB)

Lai, Peng-Yeh [Institute of Molecular Biology and Department of Life Science, National Chung Cheng University, Chiayi 621, Taiwan, ROC (China); Tsai, Chong-Bin [Institute of Molecular Biology and Department of Life Science, National Chung Cheng University, Chiayi 621, Taiwan, ROC (China); Department of Ophthalmology, Chiayi Christian Hospital, Chiayi 600, Taiwan, ROC (China); Tseng, Min-Jen, E-mail: biomjt@ccu.edu.tw [Institute of Molecular Biology and Department of Life Science, National Chung Cheng University, Chiayi 621, Taiwan, ROC (China)

2013-01-18

Highlights: ► Notch4IC modulates the ERK pathway and cell cycle to promote 3T3-L1 proliferation. ► Notch4IC facilitates 3T3-L1 differentiation by up-regulating proadipogenic genes. ► Notch4IC promotes proliferation during the early stage of 3T3-L1 adipogenesis. ► Notch4IC enhances differentiation during subsequent stages of 3T3-L1 adipogenesis. -- Abstract: Adipose tissue is composed of adipocytes, which differentiate from precursor cells in a process called adipogenesis. Many signal molecules are involved in the transcriptional control of adipogenesis, including the Notch pathway. Previous adipogenic studies of Notch have focused on Notch1 and HES1; however, the role of other Notch receptors in adipogenesis remains unclear. Q-RT-PCR analyses showed that the augmentation of Notch4 expression during the differentiation of 3T3-L1 preadipocytes was comparable to that of Notch1. To elucidate the role of Notch4 in adipogenesis, the human active form Notch4 (N4IC) was transiently transfected into 3T3-L1 cells. The expression of HES1, Hey1, C/EBPδ and PPARγ was up-regulated, and the expression of Pref-1, an adipogenic inhibitor, was down-regulated. To further characterize the effect of N4IC in adipogenesis, stable cells expressing human N4IC were established. The expression of N4IC promoted proliferation and enhanced differentiation of 3T3-L1 cells compared with those of control cells. These data suggest that N4IC promoted proliferation through modulating the ERK pathway and the cell cycle during the early stage of 3T3-L1 adipogenesis and facilitated differentiation through up-regulating adipogenic genes such as C/EBPα, PPARγ, aP2, LPL and HSL during the middle and late stages of 3T3-L1 adipogenesis.

Development and tests of fast 1-MA linear transformer driver stages

Directory of Open Access Journals (Sweden)

A. A. Kim

2009-05-01

Full Text Available In this article we present the design and test results of the most powerful, fast linear transformer driver (LTD stage developed to date. This 1-MA LTD stage consists of 40 parallel RLC (resistor R, inductor L, and capacitor C circuits called “bricks” that are triggered simultaneously; it is able to deliver ∼1  MA current pulse with a rise time of ∼100  ns into the ∼0.1-Ohm matched load. The electrical behavior of the stage can be predicted by using a simple RLC circuit, thus simplifying the designing of various LTD-based accelerators. Five 1-MA LTD stages assembled in series into a module have been successfully tested with both resistive and vacuum electron-beam diode loads.

Impact of VEGF and VEGF receptor 1 (FLT1) expression on the prognosis of stage III esophageal cancer patients after radiochemotherapy

Energy Technology Data Exchange (ETDEWEB)

Rades, D. [Dept. of Radiation Oncology, Univ. Medical Center Hamburg-Eppendorf (Germany); Dept. of Radiation Oncology, Univ. Hospital Schleswig-Holstein, Luebeck (Germany); Golke, H. [Dept. of Radiation Oncology, Univ. Medical Center Hamburg-Eppendorf (Germany); Inst. of Pathology, Univ. Medical Center Hamburg-Eppendorf (Germany); Schild, S.E. [Dept. of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States); Kilic, E. [Inst. of Pathology, Univ. Medical Center Hamburg-Eppendorf (Germany); Inst. of Pathology, Univ. Hospital Basel-Stadt (Switzerland)

2008-08-15

Background and purpose: high expression of vascular endothelial growth factor (VEGF) is negatively associated with clinical outcome. The prognostic value of VEGF receptor 1 (FLT1) is unclear. This retrospective study investigated the impact of tumor expression of VEGF and FLT1 on outcome in 68 stage III esophageal cancer patients. Material and methods: the impact of tumor VEGF and FLT expression (< 10% vs. > 10%) and five additional potential prognostic factors on overall survival (OS) and locoregional control (LC) was retrospectively evaluated. These factors included T-stage (T3 vs. T4), N-stage (NO vs. N1), treatment (radiochemotherapy plus resection vs. radiochemotherapy alone), erythropoietin (ERYPO {sup registered} 10000, Janssen-Cilag, Neuss, Germany) administration during radiotherapy, and majority of hemoglobin levels during radiotherapy (< 12 vs. {>=} 12 g/dl). Subgroup analyses were performed for patients receiving resection (R0 vs. R1/2 resection). The factors found to be significant on univariate analyses (Kaplan-Meier method, log-rank test) were included in multivariate analyses performed with the Cox proportional hazard model. Results: on univariate analysis, improved OS was associated with T3 stage (p = 0.011), surgery (p = 0.019), and hemoglobin {>=} 12 g/dl (p < 0.001). Improved LC was associated with T3 stage (p = 0.025), hemoglobin {>=} 12 g/dl (p < 0.001), and VEGF negativity (p = 0.045). On multivariate analyses, only hemoglobin maintained significance. In patients having surgery, R0 resection was significantly better than R1/2 resection for OS (p < 0.001) and LC (p < 0.001). Conclusion: preradiotherapy tumor VEGF expression appears negatively correlated with outcomes, whereas FLT1 expression appears to have no significant impact on OS and LC. (orig.)

Impact of VEGF and VEGF receptor 1 (FLT1) expression on the prognosis of stage III esophageal cancer patients after radiochemotherapy

International Nuclear Information System (INIS)

Rades, D.; Golke, H.; Schild, S.E.; Kilic, E.

2008-01-01

Background and purpose: high expression of vascular endothelial growth factor (VEGF) is negatively associated with clinical outcome. The prognostic value of VEGF receptor 1 (FLT1) is unclear. This retrospective study investigated the impact of tumor expression of VEGF and FLT1 on outcome in 68 stage III esophageal cancer patients. Material and methods: the impact of tumor VEGF and FLT expression ( 10%) and five additional potential prognostic factors on overall survival (OS) and locoregional control (LC) was retrospectively evaluated. These factors included T-stage (T3 vs. T4), N-stage (NO vs. N1), treatment (radiochemotherapy plus resection vs. radiochemotherapy alone), erythropoietin (ERYPO registered 10000, Janssen-Cilag, Neuss, Germany) administration during radiotherapy, and majority of hemoglobin levels during radiotherapy (< 12 vs. ≥ 12 g/dl). Subgroup analyses were performed for patients receiving resection (R0 vs. R1/2 resection). The factors found to be significant on univariate analyses (Kaplan-Meier method, log-rank test) were included in multivariate analyses performed with the Cox proportional hazard model. Results: on univariate analysis, improved OS was associated with T3 stage (p = 0.011), surgery (p = 0.019), and hemoglobin ≥ 12 g/dl (p < 0.001). Improved LC was associated with T3 stage (p = 0.025), hemoglobin ≥ 12 g/dl (p < 0.001), and VEGF negativity (p = 0.045). On multivariate analyses, only hemoglobin maintained significance. In patients having surgery, R0 resection was significantly better than R1/2 resection for OS (p < 0.001) and LC (p < 0.001). Conclusion: preradiotherapy tumor VEGF expression appears negatively correlated with outcomes, whereas FLT1 expression appears to have no significant impact on OS and LC. (orig.)

Implementation of the II. Stage decommissioning of A1 NPP

International Nuclear Information System (INIS)

Ficher, T.

2015-01-01

Presentation is focused on the implementation of the II. stage decommissioning of A1 NPP. Introductory part focuses on brief characteristics of the power plant with a history of operation, basic technical parameters and actions that were made after operation. The next section describes the basic schedule for decommissioning, structure of management and implementation of the II. stage decommissioning of the A1 NPP and objectives of the individual stages. The last and largest part of the presentation is devoted to detailed description of the II. stage decommissioning of the A1 NPP, its individual tasks and verbal and visual description of the activities that were performed. Presented is decommissioning of the technology and construction of external objects NPP A1 including storage tanks for liquid RAW, next are presented activities carried out in the Main Production Unit - decommissioning of non-operating technologies in various places/rooms, management of waste arising from these activities, treatment of case of A1 long-term spent fuel storage and long-term spent fuel storage. The subsequent section is devoted to the management and handling of contaminated soil, concrete and construction waste, including management of VLLW. (authors)

Parenchymal neurocysticercosis: follow-up and staging by MRI

International Nuclear Information System (INIS)

Dumas, J.L.; Visy, J.M.; Belin, C.; Gaston, A.; Goldlust, D.; Dumas, M.

1997-01-01

We describe the evolution of parenchymal cerebral cysticerci on MRI, to assess signs of early cyst degeneration. We studied 15 lesions in four treated and one untreated patient. MRI was performed before therapy and repeated in the 1st month after each course of anticysticercus drugs, every 4 months during the 1st year and then annually; the follow-up period was 8-48 months. Lesions were classified according to changes in four features: cyst content and capsule signal, gadolinium enhancement and oedema signal. We were able to recognise each of the pathological phases; five MRI stages were identified. Stage 1 showed oedema and/or nodular gadolinium enhancement in the tissue invasion phase; stage 2 was cerebrospinal fluid-like signal within a cyst in the vesicular phase; stage 3 showed a thick capsule with an impure liquid content signal and surrounding oedema, in the cystic phase; stage 4 showed the disappearance of the cyst fluid content signal in the degenerative phase; stage 5 showed a calcified lesion in the residual phase. Stage 1 lesions disappeared after therapy; the other progressed from one stage to another. Stage 4 indicated the end of viability of the parasite and determined the point after which treatment was useless. On T2-weighted images changes in the cyst content differed according to the history of the lesion; nodular low intensity followed the natural degeneration of the parasite and a mixed fluid signal with punctate low signal seemed to represent the specific result of therapy. MRI staging can help in the evaluation of indications for treatment and facilitate clinical therapeutic trials. (orig.). With 4 figs., 1 tab

Parenchymal neurocysticercosis: follow-up and staging by MRI

Energy Technology Data Exchange (ETDEWEB)

Dumas, J.L. [Dept. of Radiology, Hopital Avicenne, Bobigny (France)]|[Inst. of Tropical Neurology, Faculty of Medicine, Limoges (France); Visy, J.M. [Dept. of Neurology, Hopital Lariboisiere, Paris (France); Belin, C. [Dept. of Neurology, Hopital Avicenne, Bobigny (France); Gaston, A. [Dept. of Neuroradiology, Hopital Henri-Mondor, Creteil (France); Goldlust, D. [Dept. of Radiology, Hopital Avicenne, Bobigny (France); Dumas, M. [Inst. of Tropical Neurology, Faculty of Medicine, Limoges (France)

1997-01-01

We describe the evolution of parenchymal cerebral cysticerci on MRI, to assess signs of early cyst degeneration. We studied 15 lesions in four treated and one untreated patient. MRI was performed before therapy and repeated in the 1st month after each course of anticysticercus drugs, every 4 months during the 1st year and then annually; the follow-up period was 8-48 months. Lesions were classified according to changes in four features: cyst content and capsule signal, gadolinium enhancement and oedema signal. We were able to recognise each of the pathological phases; five MRI stages were identified. Stage 1 showed oedema and/or nodular gadolinium enhancement in the tissue invasion phase; stage 2 was cerebrospinal fluid-like signal within a cyst in the vesicular phase; stage 3 showed a thick capsule with an impure liquid content signal and surrounding oedema, in the cystic phase; stage 4 showed the disappearance of the cyst fluid content signal in the degenerative phase; stage 5 showed a calcified lesion in the residual phase. Stage 1 lesions disappeared after therapy; the other progressed from one stage to another. Stage 4 indicated the end of viability of the parasite and determined the point after which treatment was useless. On T2-weighted images changes in the cyst content differed according to the history of the lesion; nodular low intensity followed the natural degeneration of the parasite and a mixed fluid signal with punctate low signal seemed to represent the specific result of therapy. MRI staging can help in the evaluation of indications for treatment and facilitate clinical therapeutic trials. (orig.). With 4 figs., 1 tab.

SLS Block 1-B and Exploration Upper Stage Navigation System Design

Science.gov (United States)

Oliver, T. Emerson; Park, Thomas B.; Smith, Austin; Anzalone, Evan; Bernard, Bill; Strickland, Dennis; Geohagan, Kevin; Green, Melissa; Leggett, Jarred

2018-01-01

The SLS Block 1B vehicle is planned to extend NASA's heavy lift capability beyond the initial SLS Block 1 vehicle. The most noticeable change for this vehicle from SLS Block 1 is the swapping of the upper stage from the Interim Cryogenic Propulsion stage (ICPS), a modified Delta IV upper stage, to the more capable Exploration Upper Stage (EUS). As the vehicle evolves to provide greater lift capability and execute more demanding missions so must the SLS Integrated Navigation System to support those missions. The SLS Block 1 vehicle carries two independent navigation systems. The responsibility of the two systems is delineated between ascent and upper stage flight. The Block 1 navigation system is responsible for the phase of flight between the launch pad and insertion into Low-Earth Orbit (LEO). The upper stage system assumes the mission from LEO to payload separation. For the Block 1B vehicle, the two functions are combined into a single system intended to navigate from ground to payload insertion. Both are responsible for self-disposal once payload delivery is achieved. The evolution of the navigation hardware and algorithms from an inertial-only navigation system for Block 1 ascent flight to a tightly coupled GPS-aided inertial navigation system for Block 1-B is described. The Block 1 GN&C system has been designed to meet a LEO insertion target with a specified accuracy. The Block 1-B vehicle navigation system is designed to support the Block 1 LEO target accuracy as well as trans-lunar or trans-planetary injection accuracy. This is measured in terms of payload impact and stage disposal requirements. Additionally, the Block 1-B vehicle is designed to support human exploration and thus is designed to minimize the probability of Loss of Crew (LOC) through high-quality inertial instruments and Fault Detection, Isolation, and Recovery (FDIR) logic. The preliminary Block 1B integrated navigation system design is presented along with the challenges associated with

Staging of gastric adenocarcinoma using two-phase spiral CT: correlation with pathologic staging

International Nuclear Information System (INIS)

Seo, Tae Seok; Lee, Dong Ho; Ko, Young Tae; Lim, Joo Won

1998-01-01

To correlate the preoperative staging of gastric adenocarcinoma using two-phase spiral CT with pathologic staging. One hundred and eighty patients with gastric cancers confirmed during surgery underwent two-phase spiral CT, and were evaluated retrospectively. CT scans were obtained in the prone position after ingestion of water. Scans were performed 35 and 80 seconds after the start of infusion of 120mL of non-ionic contrast material with the speed of 3mL/sec. Five mm collimation, 7mm/sec table feed and 5mm reconstruction interval were used. T-and N-stage were determined using spiral CT images, without knowledge of the pathologic results. Pathologic staging was later compared with CT staging. Pathologic T-stage was T1 in 70 cases(38.9%), T2 in 33(18.3%), T3 in 73(40.6%), and T4 in 4(2.2%). Type-I or IIa elevated lesions accouted for 10 of 70 T1 cases(14.3%) and flat or depressed lesions(type IIb, IIc, or III) for 60(85.7%). Pathologic N-stage was NO in 85 cases(47.2%), N1 in 42(23.3%), N2 in 31(17.2%), and N3 in 22(12,2%). The detection rate of early gastric cancer using two-phase spiral CT was 100.0%(10 of 10 cases) among elevated lesions and 78.3%(47 of 60 cases) among flat or depressed lesions. With regard to T-stage, there was good correlation between CT image and pathology in 86 of 180 cases(47.8%). Overstaging occurred in 23.3%(42 of 180 cases) and understaging in 28.9%(52 of 180 cases). With regard to N-stage, good correlation between CT image and pathology was noted in 94 of 180 cases(52.2%). The rate of understaging(31.7%, 57 of 180 cases) was higher than that of overstaging(16.1%, 29 of 180 cases)(p<0.001). The detection rate of early gastric cancer using two-phase spiral CT was 81.4%, and there was no significant difference in detectability between elevated and depressed lesions. Two-phase spiral CT for determing the T-and N-stage of gastric cancer was not effective;it was accurate in abont 50% of cases understaging tended to occur.=20

Single and combined effects of cadmium and arsenate in Gammarus pulex (Crustacea, Amphipoda): Understanding the links between physiological and behavioural responses

Energy Technology Data Exchange (ETDEWEB)

Vellinger, Céline, E-mail: celine.vellinger@gmail.com [Laboratoire Interdisciplinaire des Environnements Continentaux (LIEC), CNRS UMR 7360, Université de Lorraine – Metz (France); Gismondi, Eric, E-mail: gismondi.eric@gmail.com [Laboratoire d’Ecologie animale et d’Ecotoxicologie, Institut de Chimie, Université de Liège, Allée du 6 Août 15, B-4000 Sart-Tilman, Liège (Belgium); Felten, Vincent, E-mail: vincent.felten@univ-lorraine.fr [Laboratoire Interdisciplinaire des Environnements Continentaux (LIEC), CNRS UMR 7360, Université de Lorraine – Metz (France); Rousselle, Philippe, E-mail: rousselle@univ-lorraine.fr [Laboratoire Interdisciplinaire des Environnements Continentaux (LIEC), CNRS UMR 7360, Université de Lorraine – Metz (France); Mehennaoui, Kahina, E-mail: meh_kahina@yahoo.fr [Laboratoire Interdisciplinaire des Environnements Continentaux (LIEC), CNRS UMR 7360, Université de Lorraine – Metz (France); Parant, Marc, E-mail: parant@univ-lorraine.fr [Laboratoire Interdisciplinaire des Environnements Continentaux (LIEC), CNRS UMR 7360, Université de Lorraine – Metz (France); Usseglio-Polatera, Philippe, E-mail: usseglio-polatera@univ-lorraine.fr [Laboratoire Interdisciplinaire des Environnements Continentaux (LIEC), CNRS UMR 7360, Université de Lorraine – Metz (France)

2013-09-15

Highlights: •Linking physiological to behavioural responses of G. pulex exposed to AsV and/or Cd. •AsV and/or Cd exposure exhibited similar biomarkers responses. •Contamination increases the mobilization of detoxification systems in gammarids. •Both changes in energy reserve use and allocation are involved in gammarid response. •Increased lipid peroxidation could be the cause of increasing gammarid mortality. -- Abstract: This study aimed at investigating the individual and interactive effects of cadmium (Cd) and arsenate (AsV) in Gammarus pulex (Crustacea, Amphipoda) through the use of several biomarkers. Individuals were exposed for 240 h to two concentrations of AsV or Cd alone, and all the possible binary mixtures of these concentrations of AsV and Cd in a complete factorial design. The pattern of the biomarkers’ responses to Cd and AsV alone or in mixture was similar in Gammarus pulex, even if the response intensity varied depending on the tested conditions. G. pulex responded to contamination with increased mobilization of the detoxification systems [i.e. γ-glutamyl-cystein ligase activity (GCL), reduced glutathione content (GSH) and metallothionein concentrations (MT)]. This response seems to imply changes in energy reserve utilization (total lipids and proteins are used prior to glycogen reserves), but also a possible energy reallocation from locomotion to detoxification processes. The observed increase in lipid peroxidation could be relied to the increasing gammarid mortality, despite the higher mobilization of detoxification systems. Even if the outcome of the complex interactions between AsV and Cd remains difficult to unravel, such studies are critically important for better assessing the effects of stressors on organisms, populations and communities in a multi-contamination context of ecosystems.

Pancreatic Metastasis in a Child Suffering with Treated Stage 4 Neuroblastoma

International Nuclear Information System (INIS)

Kim, Eun Young; Yoo, So Young; Kim, Ji Hye; Sung, Ki Woong

2008-01-01

Neuroblastoma is the most common extracranial solid tumor of childhood, and its metastasis to distant organs such as bone, bone marrow and liver is well documented. However, pancreatic metastasis of neuroblastoma has not yet been reported in the medical literature. We report here on a 4-year old boy who had a metastatic relapse in his pancreas, combined with pancreatitis, after remission of stage 4 neuroblastoma. In conclusion, we present here a very rare case of neuroblastoma that metastasized to the pancreas in a 4- year-old boy. Pancreatic metastasis should be taken into consideration for those patients who are found to have pancreatic nodules concurrent with neuroblastoma

A simplified staging system based on the radiological findings in different stages of ochronotic spondyloarthropathy

International Nuclear Information System (INIS)

Jebaraj, Isaac; Chacko, Binita Riya; Chiramel, George Koshy; Matthai, Thomas; Parameswaran, Apurve

2013-01-01

This study describes a group of 26 patients with ochronotic spondyloarthropathy who were on regular treatment and follow-up at a tertiary level hospital and proposes a simplified staging system for ochronotic spondyloarthropathy based on radiographic findings seen in the thoracolumbar spine. This proposed classification makes it easy to identify the stage of the disease and start the appropriate management at an early stage. Four progressive stages are described: an inflammatory stage (stage 1), the stage of early discal calcification (stage 2), the stage of fibrous ankylosis (stage 3), and the stage of bony ankylosis (stage 4). To our knowledge, this is the largest reported series of radiological description of spinal ochronosis, and emphasizes the contribution of the spine radiograph in the diagnosis and staging of the disease

A simplified staging system based on the radiological findings in different stages of ochronotic spondyloarthropathy

Directory of Open Access Journals (Sweden)

Isaac Jebaraj

2013-01-01

Full Text Available This study describes a group of 26 patients with ochronotic spondyloarthropathy who were on regular treatment and follow-up at a tertiary level hospital and proposes a simplified staging system for ochronotic spondyloarthropathy based on radiographic findings seen in the thoracolumbar spine. This proposed classification makes it easy to identify the stage of the disease and start the appropriate management at an early stage. Four progressive stages are described: an inflammatory stage (stage 1, the stage of early discal calcification (stage 2, the stage of fibrous ankylosis (stage 3, and the stage of bony ankylosis (stage 4. To our knowledge, this is the largest reported series of radiological description of spinal ochronosis, and emphasizes the contribution of the spine radiograph in the diagnosis and staging of the disease.

CT staging of renal cell carcinoma

International Nuclear Information System (INIS)

Spina, Juan C.; Garcia, Adriana T.; Rogondino, Jose; Spina, Juan C. h; Vidales, Valeria; Troiani, Guillermo; Iotti, Alejandro; Venditti, Julio

2002-01-01

Objective: To assess the usefulness of computerized tomography (CT) in the characterization of renal masses, in order to stage them, determine their prognosis and their appropriate clinical and/or surgical management. Material and Methods: Between 1988 and 2001, we selected 63 patients with renal tumors that had been examined by pathology. Patient's ages ranged from 16 to 88 years (25 women, 38 men). The studies were performed with a sequential helical CT, using 5 mm thickness sections every 5mm evaluating the cortico medullar and nephrographic phases. Renal tumors were characterized and staged without any knowledge about the pathological findings; subsequently the tomographic characteristics were compared to such findings. The following characteristics were evaluated: 1) mixed solid-cystic nature; 2) size; 3) borders; 4) enhancement; 5) necrosis; 6) hemorrhage; 7) central scar; 8) presence of fat; 9) collecting system; 10) capsular invasion; 11) perirenal fat invasion; 12) vessels; 13) Gerota's fascia; 14) lymph nodes; and 15) local and/or distant metastases. Results: Of the 63 tumors, 2 were complicated cysts; of the 61 remaining tumors, 10 were angiomyolipomas, 1 was a renal lymphoma, 1 was a focal xantogranulomatose pyelonephritis, 1 was a metanephric adenoma, 3 papillary renal cell carcinoma (RCC), 4 transitional cell tumors, 4 oncocytomas, 37 clear cell renal carcinoma. The CT could correctly characterize the 2 cystic tumors as such, as well as the 9 angiomyolipomas and the 4 transitional cell tumors. The 48 other tumors (1 angiomyolipoma, 1 lymphoma, 1 focal xantogranulomatose pyelonephritis, 1 metanephric adenoma, 3 papillary RCC, 4 oncocytomas, and 37 cell renal carcinomas) remaining were characterized as renal adenocarcinomas and CT staged. Conclusion: CT is a useful method to characterize renal masses since it determines their solid-cystic or fatty structure; aiding in many cases to define a surgical treatment. For the CT staging of renal tumors, the

Value of Surgery for Stage IIIa Non-small Cell Lung Cancer

Directory of Open Access Journals (Sweden)

Huihui LIU

2013-12-01

Full Text Available Background and objective Nowadays, comprehensive treatment, including surgery, chemotherapy and radiotherapy is advocated for stage III non-small cell lung cancer (NSCLC. However, many researchers have questioned the effectiveness of surgery. The aim of this study is to evaluate the effect of surgery for stage III NSCLC. Methods Between March 2002 and October 2012, 310 cases that have completed followed-up data with stage III NSCLC were received in the Peking Union Medical College Hospital. They were divided into surgical and non-surgical groups according to whether received surgery when diagnosed. In TNM staging, stage III NSCLC includes stage IIIa and IIIb, and stage IIIa NSCLC can be grouped into stage T4N0/T3-4N1M0 and T1-3N2M0 according to different N stages. Analyzed the enumeration data by Chi-Square test. Kaplan-Meier survival method was used to calculate the overall survival (OS and progression-free survival (PFS, and to draw the survival curves. A P value less than 0.05 was evaluated as statistically significant. Results Three hundred and ten stage III NSCLC patients include surgical group 189 cases and non-surgical group 121 cases. One hundred and eighty-eight stage IIIa NSCLC patients include surgical group 152 cases and non-surgical group 36 cases. In stage IIIa, stage T4N0/T3-4N1M0 had 57 patients with 44 surgical and 13 non-surgical patients, and stage T1-3N2M0 had 131 patients with 108 surgical and 23 non-surgical patients. Thirty-seven out of 121 stage IIIb NSCLC patients received surgery. They had 22 stage T4N2M0 cases and 15 stage T1-4N3M0 cases. The patient whose performance status was 0 and staging was stage IIIa was more inclined to undergo surgery. For stage IIIa NSCLC patients, the median OS of surgical and non-surgical groups were 38.9 and 21.8 months, and the median PFS of them were 19.2 and 11.9 months respectively. The difference of OS between the two groups was significant (P=0.041, but the PFS of them had no

Hypocalcemia post denosumab in patients with chronic kidney disease stage 4-5.

Science.gov (United States)

Dave, Vatsa; Chiang, Cherie Y; Booth, Jane; Mount, Peter F

2015-01-01

Denosumab, a RANK-ligand inhibitor, is an effective treatment for osteoporosis in postmenopausal women and men. Unlike the bisphosphonates, it is not excreted by the kidney. Little is known, however, about its efficacy and safety in patients with severe chronic kidney disease (CKD). A retrospective study was performed in CKD 4-5D patients from a tertiary referral hospital who were treated with denosumab between 1st January 2011 and 31st March 2014. Data collected included information about the following: CKD stage, fracture history, bone mineral density, serum calcium levels pre and post denosumab treatment, episodes of hypocalcemia, relevant medications and adverse events. Eight patients with CKD-5 and 6 patients with CKD-4 were identified (all female, mean age 77.1 ± 9.9). The mean pre-denosumab calcium value was 2.42 ± 0.12 mmol/l, PTH 20.2 ± 14.7 pmol/l and 25-OH vitamin D 69.1 ± 30.1 nmol/l. After denosumab treatment, 6/8 patients with CKD-5/5D, and 2/5 patients with CKD-4 developed severe hypocalcemia. Two patients developed direct adverse complications of hypocalcemia (seizure, laryngospasm, prolonged QTc). Among the patients who developed hypocalcemia, the median time to serum calcium nadir was 21 days and the median time to correction of hypocalcemia was 71 days. Treatment of hypocalcemia required large doses of oral calcium and calcitriol, and increases in dialysate calcium concentration. A high rate of severe hypocalcemia was observed in patients with advanced CKD treated with denosumab. If denosumab is used in patients with severe CKD, close monitoring and aggressive replacement of calcium and calcitriol is required to avoid the development of hypocalcemia.

[The mechanisms of p21WAF1/Cip-1 expression in MOLT-4 cell line induced by TSA].

Science.gov (United States)

Song, Yi; Liu, Mei-Ju; Zhao, Guo-Wei; Qian, Jun-Jie; Dong, Yan; Liu, Hua; Sun, Guo-Jing; Mei, Zhu-Zhong; Liu, Bin; Tian, Bao-Lei; Sun, Zhi-Xian

2005-04-01

To investigate the function and molecular mechanism of p21(WAF1/Cip-1) expression in MOLT-4 cells induced by HDAC inhibitor TSA, the expression pattern of p21(WAF1/Cip-1) and the distribution of cell cycle in TSA treated cells were analyzed. The results showed that TSA could effectively induce G(2)/M arrest and apoptosis of MOLT-4 cells. Kinetic experiments demonstrated that p21(WAF1/Cip-1) were upregulated quickly before cell arrested in G(2)/M and began decreasing at the early stage of apoptosis. Meanwhile, the proteasome inhibitor MG-132 could inhibit the decrease of p21(WAF1/Cip-1) at the early stage of apoptosis, which showed that proteasome pathway involved in p21(WAF1/Cip-1) degradation during the TSA induced G(2)/M arrest and apoptosis responses. This study also identified that the protein level of p21(WAF1/Cip-1) was highly associated with the cell cycle change induced by TSA. Compared to cells treated by TSA only, exposure MOLT-4 cells to TSA meanwhile treatment with MG-132 increased the protein level of p21(WAF1/Cip-1) and increased the numbers of cell in G(2)/M-phase, whereas the cell apoptosis were delayed. It is concluded that p21(WAF1/Cip-1) plays a significant role in G(2)/M arrest and apoptosis signaling induced by TSA in MOLT-4 cells.

Preliminary technical data summary for the Defense Waste Processing Facility, Stage 1

International Nuclear Information System (INIS)

1980-09-01

This Preliminary Technical Data Summary presents the technical basis for design of Stage 1 of the Staged Defense Waste Processing Facility (DWPF), a process to efficiently immobilize the radionuclides in Savannah River Plant (SRP) high-level liquid waste. The radionuclides in SRP waste are present in sludge that has settled to the bottom of waste storage tanks and in crystallized salt and salt solution (supernate). Stage 1 of the DWPF receives washed, aluminum dissolved sludge from the waste tank farms and immobilizes it in a borosilicate glass matrix. The supernate is retained in the waste tank farms until completion of Stage 2 of the DWPF at which time it filtered and decontaminated by ion exchange in the Stage 2 facility. The decontaminated supernate is concentrated by evaporation and mixed with cement for burial. The radioactivity removed from the supernate is fixed in borosilicate glass along with the sludge. This document gives flowsheets, material, and curie balances, material and curie balance bases, and other technical data for design of the Stage 1 DWPF

Saturn V First Stage (S-1C) At MSFC

Science.gov (United States)

1960-01-01

This small group of unidentified officials is dwarfed by the gigantic size of the Saturn V first stage (S-1C) at the shipping area of the Manufacturing Engineering Laboratory at Marshall Space Flight Center in Huntsville, Alabama. The towering 363-foot Saturn V was a multi-stage, multi-engine launch vehicle standing taller than the Statue of Liberty. Altogether, the Saturn V engines produced as much power as 85 Hoover Dams.

Phase III Randomized Study of 4 Weeks of High-Dose Interferon-α-2b in Stage T2bNO, T3a-bNO, T4a-bNO, and T1-4N1a-2a (microscopic) Melanoma: A Trial of the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group (E1697).

Science.gov (United States)

Agarwala, Sanjiv S; Lee, Sandra J; Yip, Waiki; Rao, Uma N; Tarhini, Ahmad A; Cohen, Gary I; Reintgen, Douglas S; Evans, Terry L; Brell, Joanna M; Albertini, Mark R; Atkins, Michael B; Dakhil, Shaker R; Conry, Robert M; Sosman, Jeffrey A; Flaherty, Lawrence E; Sondak, Vernon K; Carson, William E; Smylie, Michael G; Pappo, Alberto S; Kefford, Richard F; Kirkwood, John M

2017-03-10

Purpose To test the efficacy of 4 weeks of intravenous (IV) induction with high-dose interferon (IFN) as part of the Eastern Cooperative Oncology Group regimen compared with observation (OBS) in patients with surgically resected intermediate-risk melanoma. Patients and Methods In this intergroup international trial, eligible patients had surgically resected cutaneous melanoma in the following categories: (1) T2bN0, (2) T3a-bN0, (3) T4a-bN0, and (4) T1-4N1a-2a (microscopic). Patients were randomly assigned to receive IFN α-2b at 20 MU/m 2 /d IV for 5 days (Monday to Friday) every week for 4 weeks (IFN) or OBS. Stratification factors were pathologic lymph node status, lymph node staging procedure, Breslow depth, ulceration of the primary lesion, and disease stage. The primary end point was relapse-free survival. Secondary end points included overall survival, toxicity, and quality of life. Results A total of 1,150 patients were randomly assigned. At a median follow-up of 7 years, the 5-year relapse-free survival rate was 0.70 (95% CI, 0.66 to 0.74) for OBS and 0.70, (95% CI, 0.66 to 0.74) for IFN ( P = .964). The 5-year overall survival rate was 0.83 (95% CI, 0.79 to 0.86) for OBS and 0.83 (95% CI, 0.80 to 0.86) for IFN ( P = .558). Treatment-related grade 3 and higher toxicity was 4.6% versus 57.9% for OBS and IFN, respectively ( P weeks of IV induction as part of the Eastern Cooperative Oncology Group high-dose IFN regimen is not better than OBS alone for patients with intermediate-risk melanoma as defined in this trial.

Sites of extranodal involvement are prognostic in patients with stage 1 follicular lymphoma.

Science.gov (United States)

Shastri, Aditi; Janakiram, Murali; Mantzaris, Ioannis; Yu, Yiting; Londono, Jaime S; Verma, Amit K; Barta, Stefan K

2017-10-03

Follicular lymphoma (FL) is the most common indolent B cell lymphoma in the United States and a quarter of patients present with stage I disease. The objective of this study was to examine if primary site of disease influences survival in early stage lymphoma. The most common extranodal primary sites were the integumentary system (8%), followed by the GI tract (6.4%) and head & neck (5.6%). We stratified patients into a pre-rituximab era (1983-1998) and the rituximab era (1999-2011). In multivariable analysis, integumentary disease was associated with better overall survival (Hazard Ratio [HR], 0.77; Confidence Interval [CI], 0.66-0.9) while primary site FL of the nervous system (HR, 2.40; CI, 1.72-3.38) and the musculoskeletal system (HR, 2.14; CI, 1.44-3.18) were associated with worse overall survival when compared to primary nodal FL. Treatment in the pre-rituximab era, male gender and older age at diagnosis were associated with worse survival. We queried the SEER database from 1983 to 2011. We included all adult patients (>18 years) with histologically confirmed stage I FL, active follow-up, and a single primary tumor. A total of 9,865 patients met eligibility criteria, with 2520 (25%) having an extranodal primary site. We classified the primary sites by organ or anatomic location into 11 sites. Primary site of disease is a prognostic factor for patients with early stage FL and may help identify subsets of patients that could benefit from early, aggressive treatment.

Recommendations for clinical staging (cTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals

Science.gov (United States)

Rice, Thomas W.; Ishwaran, Hemant; Blackstone, Eugene H.; Hofstetter, Wayne L.; Kelsen, David P.; Apperson-Hansen, Carolyn

2017-01-01

SUMMARY We report analytic and consensus processes that produced recommendations for clinical stage groups (cTNM) of esophageal and esophagogastric junction cancer for the AJCC/UICC cancer staging manuals, 8th edition. The Worldwide Esophageal Cancer Collaboration (WECC) provided data on 22,123 clinically staged patients with epithelial esophageal cancers. Risk-adjusted survival for each patient was developed using random survival forest analysis from which (1) data-driven clinical stage groups were identified wherein survival decreased monotonically and was distinctive between and homogeneous within groups and (2) data-driven anatomic clinical stage groups based only on cTNM. The AJCC Upper GI Task Force, by smoothing, simplifying, expanding, and assessing clinical applicability, produced (3) consensus clinical stage groups. Compared with pTNM, cTNM survival was “pinched,” with poorer survival for early cStage groups and better survival for advanced ones. Histologic grade was distinctive for data-driven grouping of cT2N0M0 squamous cell carcinoma (SCC) and cT1-2N0M0 adenocarcinoma, but consensus removed it. Grouping was different by histopathologic cell type. For SCC, cN0-1 was distinctive for cT3 but not cT1-2, and consensus removed cT4 subclassification and added subgroups 0, IVA, and IVB. For adenocarcinoma, N0-1 was distinctive for cT1-2 but not cT3-4a, cStage II subgrouping was necessary (T1N1M0 [IIA] and T2N0M0 [IIB]), advanced cancers cT3-4aN0-1M0 plus cT2N1M0 comprised cStage III, and consensus added subgroups 0, IVA, and IVB. Treatment decisions require accurate cStage, which differs from pStage. Understaging and overstaging are problematic, and additional factors, such as grade, may facilitate treatment decisions and prognostication until clinical staging techniques are uniformly applied and improved. PMID:27905171

Recommendations for clinical staging (cTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals.

Science.gov (United States)

Rice, Thomas W; Ishwaran, Hemant; Blackstone, Eugene H; Hofstetter, Wayne L; Kelsen, David P; Apperson-Hansen, Carolyn

2016-11-01

We report analytic and consensus processes that produced recommendations for clinical stage groups (cTNM) of esophageal and esophagogastric junction cancer for the AJCC/UICC cancer staging manuals, 8th edition. The Worldwide Esophageal Cancer Collaboration (WECC) provided data on 22,123 clinically staged patients with epithelial esophageal cancers. Risk-adjusted survival for each patient was developed using random survival forest analysis from which (1) data-driven clinical stage groups were identified wherein survival decreased monotonically and was distinctive between and homogeneous within groups and (2) data-driven anatomic clinical stage groups based only on cTNM. The AJCC Upper GI Task Force, by smoothing, simplifying, expanding, and assessing clinical applicability, produced (3) consensus clinical stage groups. Compared with pTNM, cTNM survival was "pinched," with poorer survival for early cStage groups and better survival for advanced ones. Histologic grade was distinctive for data-driven grouping of cT2N0M0 squamous cell carcinoma (SCC) and cT1-2N0M0 adenocarcinoma, but consensus removed it. Grouping was different by histopathologic cell type. For SCC, cN0-1 was distinctive for cT3 but not cT1-2, and consensus removed cT4 subclassification and added subgroups 0, IVA, and IVB. For adenocarcinoma, N0-1 was distinctive for cT1-2 but not cT3-4a, cStage II subgrouping was necessary (T1N1M0 [IIA] and T2N0M0 [IIB]), advanced cancers cT3-4aN0-1M0 plus cT2N1M0 comprised cStage III, and consensus added subgroups 0, IVA, and IVB. Treatment decisions require accurate cStage, which differs from pStage. Understaging and overstaging are problematic, and additional factors, such as grade, may facilitate treatment decisions and prognostication until clinical staging techniques are uniformly applied and improved. © 2016 International Society for Diseases of the Esophagus.

Disruptive cell cycle regulation involving epigenetic downregulation of Cdkn2a (p16Ink4a) in early-stage liver tumor-promotion facilitating liver cell regeneration in rats

International Nuclear Information System (INIS)

Tsuchiya, Takuma; Wang, Liyun; Yafune, Atsunori; Kimura, Masayuki; Ohishi, Takumi; Suzuki, Kazuhiko; Mitsumori, Kunitoshi; Shibutani, Makoto

2012-01-01

Cell cycle aberration was immunohistochemically examined in relation to preneoplastic liver cell foci expressing glutathione S-transferase placental form (GST-P) at early stages of tumor-promotion in rats with thioacetamide (TAA), a hepatocarcinogen facilitating liver cell regeneration. Immunoexpression of p16 Ink4a following exposure to other hepatocarcinogens/promoters and its DNA methylation status were also analyzed during early and late tumor-promotion stages. GST-P + liver cell foci increased cell proliferation and decreased apoptosis when compared with surrounding liver cells. In concordance with GST-P + foci, checkpoint proteins at G 1 /S (p21 Cip1 , p27 Kip1 and p16 Ink4a ) and G 2 /M (phospho-checkpoint kinase 1, Cdc25c and phospho-Wee1) were either up- or downregulated. Cellular distribution within GST-P + foci was either increased or decreased with proteins related to G 2 -M phase or DNA damage (topoisomerase IIα, phospho-histone H2AX, phospho-histone H3 and Cdc2). In particular, p16 Ink4a typically downregulated in GST-P + foci and regenerative nodules at early tumor-promotion stage with hepatocarcinogens facilitating liver cell regeneration and in neoplastic lesions at late tumor-promotion stage with hepatocarcinogens/promoters irrespective of regenerating potential. Hypermethylation at exon 2 of Cdkn2a was detected at both early- and late-stages. Thus, diverse disruptive expression of G 1 /S and G 2 /M proteins, which allows for clonal selection of GST-P + foci, results in the acquisition of multiple aberrant phenotypes to disrupt checkpoint function. Moreover, increased DNA-damage responses within GST-P + foci may be the signature of genetic alterations. Intraexonic hypermethylation may be responsible for p16 Ink4a -downregulation, which facilitates cell cycle progression in early preneoplastic lesions produced by repeated cell regeneration and late-stage neoplastic lesions irrespective of the carcinogenic mechanism.

[Value of surgery for stage IIIa non-small cell lung cancer].

Science.gov (United States)

Liu, Huihui; Wang, Mengzhao; Hu, Ke; Xu, Yan; Ma, Manjiao; Zhong, Wei; Zhao, Jing; Li, Longyun; Wang, Huazhu

2013-12-01

Nowadays, comprehensive treatment, including surgery, chemotherapy and radiotherapy is advocated for stage III non-small cell lung cancer (NSCLC). However, many researchers have questioned the effectiveness of surgery. The aim of this study is to evaluate the effect of surgery for stage III NSCLC. Between March 2002 and October 2012, 310 cases that have completed followed-up data with stage III NSCLC were received in the Peking Union Medical College Hospital. They were divided into surgical and non-surgical groups according to whether received surgery when diagnosed. In TNM staging, stage III NSCLC includes stage IIIa and IIIb, and stage IIIa NSCLC can be grouped into stage T4N0/T3-4N1M0 and T1-3N2M0 according to different N stages. Analyzed the enumeration data by Chi-Square test. Kaplan-Meier survival method was used to calculate the overall survival (OS) and progression-free survival (PFS), and to draw the survival curves. A P value less than 0.05 was evaluated as statistically significant. Three hundred and ten stage III NSCLC patients include surgical group 189 cases and non-surgical group 121 cases. One hundred and eighty-eight stage IIIa NSCLC patients include surgical group 152 cases and non-surgical group 36 cases. In stage IIIa, stage T4N0/T3-4N1M0 had 57 patients with 44 surgical and 13 non-surgical patients, and stage T1-3N2M0 had 131 patients with 108 surgical and 23 non-surgical patients. Thirty-seven out of 121 stage IIIb NSCLC patients received surgery. They had 22 stage T4N2M0 cases and 15 stage T1-4N3M0 cases. The patient whose performance status was 0 and staging was stage IIIa was more inclined to undergo surgery. For stage IIIa NSCLC patients, the median OS of surgical and non-surgical groups were 38.9 and 21.8 months, and the median PFS of them were 19.2 and 11.9 months respectively. The difference of OS between the two groups was significant (P=0.041), but the PFS of them had no significant difference (P=0.209). For stage T4N0/T3-4N1M0 which

Synthesis of β-1,4-Linked Galactan Side-Chains of Rhamnogalacturonan I

DEFF Research Database (Denmark)

Andersen, Mathias Christian Franch; Kracun, Stjepan; Rydahl, Maja

2016-01-01

The synthesis of linear- and (1→6)-branched-β-(1→4)-D-galactans, side chains of the pectic polysaccharide rhamnogalacturonan I is described. The strategy relies on iterative couplings of n-pentenyl disaccharides followed by a late stage glycosylation of a common hexasaccharide core. Reaction...

Analysis of the prognostic factors for low rectal cancer with the pT1-2NxM0 stage after abdominoperineal resection.

Science.gov (United States)

Zhang, Xing-mao; Ma, Chao; Sun, Da-yong; Wang, Zheng; Zhou, Zhi-xiang

2015-01-01

This study was designed to explore the factors influencing local recurrence and survival for low rectal cancer with pT1-2NxM0 stage after an abdominoperineal resection (APR). Data of 429 patients confirmed to have pT1-2NxM0 after APR were reviewed. The recurrence rate in patients with intraoperative perforation, less than 12 lymph nodes (LNs) harvested, T2 staging, and positive circumferential resection margin (CRM) was 25.1, 19.9, 9.5, and 26.1% compared with 6.9, 7.0, 0, and 5.8% in patients with no perforation, 12 or more LNs harvested, T1, and negative CRM. The 5-year survival rate in patients with age of at least 70, perforation, less than 12 LNs harvested, T2, and positive CRM was 71.1, 60.8, 58.8, 69.9, and 46.0%, but 73.4, 73.5, 73.8, 89.4, and 75.0% in patients with age less than 70, no perforation, 12 or more LNs harvested, T1, and negative CRM. Meanwhile, patients with N0, N1, and N2 had a survival rate of 90.7, 69.9, and 63.9%. Multivariate analysis showed that perforation (PCRM status (P=0.002) were associated with local recurrence, whereas age of the patients (P=0.023), N staging (PCRM status (P=0.004) were associated with survival. APR was affected by patients' age, operation performer, perforation, number of LNs harvested, T staging, N staging, differentiation, and CRM status. Perforation, number of LNs harvested, T staging, differentiation, and CRM status were independent factors for recurrence; meanwhile, age of the patients, N staging, differentiation, and CRM status were independent factors influencing survival.

The Outcome of Postoperative Radiation Therapy for Patients with Stage II Pancreatic Cancer (T3 or N1 Disease)

Energy Technology Data Exchange (ETDEWEB)

Kim, Sang Won; Chun, Misun; Kim, Myung Wook; Kim, Wook Hwan; Kang, Seok Yun; Kang, Seung Hee; Oh, Young Taek; Lee, Sunyoung; Yang, Juno [Ajou University School of Medicine, Suwon (Korea, Republic of)

2007-12-15

Purpose: To analyze retrospectively the outcome of postoperative radiation therapy with or without concurrent chemotherapy for curatively resected stage II pancreatic cancer with T3 or N1 disease. Materials and Methods: Between January 1996 and December 2005, twenty-eight patients completed adjuvant radiation therapy at Ajou University Hospital. The patients had either pathologic T3 stage or N1 stage. The radiation target volume encompassed the initial tumor bed identified preoperatively, resection margin area and celiac nodal area. In the case of N1 patients, the radiation field extended to the lower margin of the L3 vertebra for covering both para-aortic lymph nodes bearing area. The median total radiation dose was 50 Gy. Ten patients received concurrent chemotherapy. Results: Thirteen patients (46%) showed loco-regional recurrences. The celiac axis nodal area was the most frequent site (4 patients). Five patients showed both loco-regional recurrence and a distant metastasis. Patients with positive lymph nodes had a relatively high probability of a distant metastasis (57.1%). Patients that had a positive resection margin showed a relatively high local failure rate (57.1%). The median disease-free survival period of all patients was 6 months and the 1- and 2-year disease free survival rates were 27.4% and 8.2%, respectively. The median overall survival period was 9 months. The 2- and 3-year overall survival rates were 31.6% and 15.8%, respectively. Conclusion: The pancreatic cancer patients with stage II had a high risk of local failure and a high risk of a distant metastasis. We suggest the concurrent use of an effective radiation-sensitizing chemotherapeutic drug and adjuvant chemotherapy after postoperative radiation therapy for the treatment of patients with stage II pancreatic cancer.

The Outcome of Postoperative Radiation Therapy for Patients with Stage II Pancreatic Cancer (T3 or N1 Disease)

International Nuclear Information System (INIS)

Kim, Sang Won; Chun, Misun; Kim, Myung Wook; Kim, Wook Hwan; Kang, Seok Yun; Kang, Seung Hee; Oh, Young Taek; Lee, Sunyoung; Yang, Juno

2007-01-01

Purpose: To analyze retrospectively the outcome of postoperative radiation therapy with or without concurrent chemotherapy for curatively resected stage II pancreatic cancer with T3 or N1 disease. Materials and Methods: Between January 1996 and December 2005, twenty-eight patients completed adjuvant radiation therapy at Ajou University Hospital. The patients had either pathologic T3 stage or N1 stage. The radiation target volume encompassed the initial tumor bed identified preoperatively, resection margin area and celiac nodal area. In the case of N1 patients, the radiation field extended to the lower margin of the L3 vertebra for covering both para-aortic lymph nodes bearing area. The median total radiation dose was 50 Gy. Ten patients received concurrent chemotherapy. Results: Thirteen patients (46%) showed loco-regional recurrences. The celiac axis nodal area was the most frequent site (4 patients). Five patients showed both loco-regional recurrence and a distant metastasis. Patients with positive lymph nodes had a relatively high probability of a distant metastasis (57.1%). Patients that had a positive resection margin showed a relatively high local failure rate (57.1%). The median disease-free survival period of all patients was 6 months and the 1- and 2-year disease free survival rates were 27.4% and 8.2%, respectively. The median overall survival period was 9 months. The 2- and 3-year overall survival rates were 31.6% and 15.8%, respectively. Conclusion: The pancreatic cancer patients with stage II had a high risk of local failure and a high risk of a distant metastasis. We suggest the concurrent use of an effective radiation-sensitizing chemotherapeutic drug and adjuvant chemotherapy after postoperative radiation therapy for the treatment of patients with stage II pancreatic cancer

NASAwide electronic publishing system: Prototype STI electronic document distribution, stage-4 evaluation report

Science.gov (United States)

Tuey, Richard C.; Collins, Mary; Caswell, Pamela; Haynes, Bob; Nelson, Michael L.; Holm, Jeanne; Buquo, Lynn; Tingle, Annette; Cooper, Bill; Stiltner, Roy

1996-01-01

This evaluation report contains an introduction, seven chapters, and five appendices. The Introduction describes the purpose, conceptual frame work, functional description, and technical report server of the STI Electronic Document Distribution (EDD) project. Chapter 1 documents the results of the prototype STI EDD in actual operation. Chapter 2 documents each NASA center's post processing publication processes. Chapter 3 documents each center's STI software, hardware, and communications configurations. Chapter 7 documents STI EDD policy, practices, and procedures. The appendices, which arc contained in Part 2 of this document, consist of (1) STI EDD Project Plan, (2) Team members, (3) Phasing Schedules, (4) Accessing On-line Reports, and (5) Creating an HTML File and Setting Up an xTRS. In summary, Stage 4 of the NASAwide Electronic Publishing System is the final phase of its implementation through the prototyping and gradual integration of each NASA center's electronic printing systems, desktop publishing systems, and technical report servers to be able to provide to NASA's engineers, researchers, scientists, and external users the widest practicable and appropriate dissemination of information concerning its activities and the result thereof to their work stations.

Synthesis and research of the physical-chemical properties of 5-((2-bromphenyl-4-amino-4H-1,2,4-triazole-3-ylthioacetic acid salts

Directory of Open Access Journals (Sweden)

Ye. S. Pruglo

2018-03-01

Full Text Available At this stage of the development of modern science the scientists get a lot of questions in the field of medicine and pharmacy, and one of the most important among them is the study and search of new ways of synthesis of high-performance and low-toxic substances. Special attention is paid to 1,2,4-triazole and xanthine. On their basis some medical drugs were made, which are widely used in medicine. The aim of this work was the synthesis and study of properties of salts of 5-(2-bromophenyl-4-amino-4H-1,2,4-triazole-3-ylthioacetic acid. Methods and results. As starting material theophylline was selected. Through a number of stages 5-(2-bromphenyl-4-amino-4H-1,2,4-triazole-3-thion was obtained. By the reaction of neutralization the salts with organic and inorganic bases were obtained. The physical-chemical properties of the compounds were determined. The structure of the substances was confirmed by elemental analysis on an Elementar Vario L cube (CHNS instrument; IR spectra (4000–400 cm-1 were taken on the ALPHA-T modules of the Bruker ALPHA FT-IR spectrometer. The 1H NMR spectra of the compounds were recorded using a Varian Mercury VX 200 spectrometer (solvent – DMSO-d6, internal standard: tetramethylsilane. The formation of salts was confirmed by the signals of the corresponding protonated amines. Chromato-mass spectral studies were carried out on the LC MS: Agilent 1260 Infinity HPLC System , ionization method – chemical ionization at atmospheric pressure (APCI. Conclusions. The interaction of the resulting thiol with monochloracetic acid in aqueous solution with double quantity of alkali and subsequent neutralization leads to corresponding carboxylic acid obtaining. It was confirmed that the greatest outputs of salts as the reaction products were observed when using water as the solvent with the subsequent replacement of acetone. the optimum conditions of obtaining salts of 5-(2-bromophenyl-4-amino-4H-1,2,4-triazole-3-ylthioacetic acid

A comparison of treating metabolic acidosis in CKD stage 4 hypertensive kidney disease with fruits and vegetables or sodium bicarbonate.

Science.gov (United States)

Goraya, Nimrit; Simoni, Jan; Jo, Chan-Hee; Wesson, Donald E

2013-03-01

Current guidelines recommend Na(+)-based alkali for CKD with metabolic acidosis and plasma total CO2 (PTCO2) < 22 mM. Because diets in industrialized societies are typically acid-producing, we compared base-producing fruits and vegetables with oral NaHCO3 (HCO3) regarding the primary outcome of follow-up estimated GFR (eGFR) and secondary outcomes of improved metabolic acidosis and reduced urine indices of kidney injury. Individuals with stage 4 (eGFR, 15-29 ml/min per 1.73 m(2)) CKD due to hypertensive nephropathy, had a PTCO2 level < 22 mM, and were receiving angiotensin-converting enzyme inhibition were randomly assigned to 1 year of daily oral NaHCO3 at 1.0 mEq/kg per day (n=35) or fruits and vegetables dosed to reduce dietary acid by half (n=36). Plasma cystatin C-calculated eGFR did not differ at baseline and 1 year between groups. One-year PTCO2 was higher than baseline in the HCO3 group (21.2±1.3 versus 19.5±1.5 mM; P<0.01) and the fruits and vegetables group (19.9±1.7 versus 19.3±1.9 mM; P<0.01), consistent with improved metabolic acidosis, and was higher in the HCO3 than the fruits and vegetable group (P<0.001). One-year urine indices of kidney injury were lower than baseline in both groups. Plasma [K(+)] did not increase in either group. One year of fruits and vegetables or NaHCO3 in individuals with stage 4 CKD yielded eGFR that was not different, was associated with higher-than-baseline PTCO2, and was associated with lower-than-baseline urine indices of kidney injury. The data indicate that fruits and vegetables improve metabolic acidosis and reduce kidney injury in stage 4 CKD without producing hyperkalemia.

Italian results for stages 1A and 2

International Nuclear Information System (INIS)

Di Francesca, R.

1990-01-01

This report presents the results on Stages 1A and 2 CRP examples. The examples have been solved by SISCO and HARMONIE codes, which are used for mechanical equilibrium calculations of fast reactor cores at ENEA Fast Reactor Department. (author). 9 figs, 12 tabs

Installation Restoration Program. Phase 2. Confirmation/Quantification. Stage 1. Air Force Plant 4, Fort Worth, Texas. Volume 3. Appendix A-1 (Continued).

Science.gov (United States)

1987-12-01

GAO 0 2L -4e- - Lq*Lio rol -4 1 IOU CI S W a G-v a. IV0 0 J= C. Ic LG 4sa C...8217 ’ ~ -i CIj -43j ~LU . l co r I_- z3 335 0- C= cu w- CDP aIC. *I lr_ - CkIJ LA-. n= C G C=> gao ’ GeL) =31 CAEl = C- C-10. LLaJ 1= w CL -* I t CI or SLLJ...6- Z u - a a qcrLLJ < nC Liu~ LI i LL.J CL. w <r LL <r 03 440 -x C= cn z4 -. - XM Z~ A ~ ’’ ~ "~’ , 4 *.\\~.S~4’N’~~’ - Iz JINI 1 *~ I- LLW W, a,

Synthesis, physical and chemical properties, antihypoxic activity of some 5-[((5-(adamantane-1-yl-4-R-4H-1,2,4-triazole-3-ylthiomethyl]-N-R1-1,3,4-thiadiazole-2-amines and 5-[((5-(adamantane-1-yl-4-R-4H-1,2,4-triazole-3-ylthiomethyl]-4-R1-4H-1,2,4-t

Directory of Open Access Journals (Sweden)

V. M. Odyntsova

2018-03-01

Full Text Available Today, an increase of natural and technogenic situations leads to the disorders of the central nervous system, functional-metabolic processes, vascular diseases, in particular, acute cerebral blood flow disorders. In addition, the changes occurring on the molecular and cellular levels are in the basis of the functional violations of individual systems and the organism as a whole. Hypoxia not only complicates the disease course, but in most cases, determines its outcome. The important role in the fight against hypoxia belongs to antioxidants, which improve the circulating oxygen utilization by the body, reduce its need for the organs and tissues, which is not only expedient but necessary for the treatment of many acute and chronic pathological processes. So, the frequency of the hypoxic states and a wide range of factors causing them determine the relevance of new ways and methods finding to overcome the oxygen deficiency. The aim of this work is the purposeful search of some 5-[((5-(adamantane-1-yl-4-R-4H-1,2,4-triazole-3-ylthiomethyl]-N-R1-1,3,4-thiadiazole-2-amines and 5-[((5-(adamantane-1-yl-4-R-4H-1,2,4-triazole-3-ylthiomethyl]-4-R1-4H-1,2,4-triazole-3-thiols, the study of their physical and chemical properties and pharmacological screening of the antihypoxic activity of the obtained compounds. Materials and methods. The study of physical and chemical properties was conducted on certified and licensed modern equipment. Antihypoxic activity was studied during the modeling process of hypoxia with hypercapnia. Mexidol was used as a comparison drug in studies at a dose of 100 mg/kg. Results. As the result of the study, it was found that the synthesized compounds and the comparison drug influenced on rats’ life span differently. Compounds, the antihypoxic activity of which exceeded control have been discovered, and others’ were at the level of Mexidol. A number of compounds showed a somewhat less activity in comparison with control, and two

Accuracy of preoperative CT T staging of renal cell carcinoma: which features predict advanced stage?

International Nuclear Information System (INIS)

Bradley, A.J.; MacDonald, L.; Whiteside, S.; Johnson, R.J.; Ramani, V.A.C.

2015-01-01

Aims: To characterise CT findings in renal cell carcinoma (RCC), and establish which features are associated with higher clinical T stage disease, and to evaluate patterns of discrepancy between radiological and pathological staging of RCC. Materials and methods: Preoperative CT studies of 92 patients with 94 pathologically proven RCCs were retrospectively reviewed. CT stage was compared with pathological stage using the American Joint Committee on Cancer (AJCC), 7 th edition (2010). The presence or absence of tumour necrosis, perinephric fat standing, thickening of Gerota's fascia, collateral vessels were noted, and correlated with pT stage. The sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) for predicting pT stage ≥pT3a were derived separately for different predictors using cross-tabulations. Results: Twenty-four lesions were pathological stage T1a, 21 were T1b, seven were T2a, 25 were T3a, 11 were T3b, four were T3c, and two were T4. There were no stage T2b. Sixty-three (67%) patients had necrosis, 27 (29%) thickening of Gerota's fascia (1 T1a), 25 had collateral vessels (0 T1a), 28 (30%) had fat stranding of <2 mm, 20 (21%) of 2–5mm and one (1%) of >5 mm. For pT stage ≥pT3a, the presence of perinephric fat stranding had a sensitivity, specificity, PPV and NPV of 74%, 65%, 63%, and 76%, respectively. Presence of tumour necrosis had a sensitivity, specificity, PPV, and NPV of 81%, 44%, 54%, and 72%, respectively. Thickening of Gerota's fascia had a sensitivity, specificity, PPV, and NPV of 52%, 90%, 81% and 70%, respectively; and enlarged collateral vessels had a sensitivity, specificity, PPV, and NPV value of 52%, 94%, 88%, and 71% respectively. Conclusion: The presence of perinephric stranding and tumour necrosis were not reliable signs for pT stage >T3a. Thickening of Gerota's fascia and the presence of collateral vessels in the peri- or paranephric fat had 90% and 94% specificity, with 82% and 88

1st Stage Separation Aerodynamics Of VEGA Launcher

Science.gov (United States)

Genito, M.; Paglia, F.; Mogavero, A.; Barbagallo, D.

2011-05-01

VEGA is an European launch vehicle under development by the Prime Contractor ELV S.p.A. in the frame of an ESA contract. It is constituted by four stages, dedicated to the scientific/commercial market of small satellites (300 ÷ 2500 kg) into Low Earth Orbits, with inclinations ranging from 5.2° up to Sun Synchronous Orbits and with altitude ranging from 300 to 1500 km. Aim of this paper is to present a study of flow field due to retro-rockets impingement during the 1st stage VEGA separation phase. In particular the main goal of the present work is to present the aerodynamic activities performed for the justification of the separation phase.

Zebrafish hoxd4a acts upstream of meis1.1 to direct vasculogenesis, angiogenesis and hematopoiesis.

Directory of Open Access Journals (Sweden)

Aseervatham Anusha Amali

Full Text Available Mice lacking the 4th-group paralog Hoxd4 display malformations of the anterior vertebral column, but are viable and fertile. Here, we report that zebrafish embryos having decreased function of the orthologous hoxd4a gene manifest striking perturbations in vasculogenesis, angiogenesis and primitive and definitive hematopoiesis. These defects are preceded by reduced expression of the hemangioblast markers scl1, lmo2 and fli1 within the posterior lateral plate mesoderm (PLM at 13 hours post fertilization (hpf. Epistasis analysis revealed that hoxd4a acts upstream of meis1.1 but downstream of cdx4 as early as the shield stage in ventral-most mesoderm fated to give rise to hemangioblasts, leading us to propose that loss of hoxd4a function disrupts hemangioblast specification. These findings place hoxd4a high in a genetic hierarchy directing hemangioblast formation downstream of cdx1/cdx4 and upstream of meis1.1. An additional consequence of impaired hoxd4a and meis1.1 expression is the deregulation of multiple Hox genes implicated in vasculogenesis and hematopoiesis which may further contribute to the defects described here. Our results add to evidence implicating key roles for Hox genes in their initial phase of expression early in gastrulation.

No advanced retinopathy of prematurity stages 4 or 5 in a large high-risk German cohort.

Science.gov (United States)

Muether, Philipp S; Kribs, Angela; Hahn, Moritz; Schumacher, Jasmin; Eifinger, Frank; Kirchhof, Bernd; Roth, Bernhard; Fauser, Sascha

2012-03-01

Retinopathy of prematurity (ROP) remains a major cause of juvenile blindness. As screening recommendations are refined, decreasing gestational age (GA) and birth weight (BW) constitute an increasing risk for ROP. This retrospective case series reviews the screening results of a very immature cohort in Germany. We conducted ROP screening according to the German guidelines of 1999: all preterm infants with a GA of 3 days, were assigned for screening. Dense laser coagulation was performed according to the current treatment criteria. All 767 consecutive inborn (patients born at the Department of Neonatology, University Hospital of Cologne, Germany) preterm infants of a tertiary medical centre of maximum care underwent complete screening from 2001 to 2009. The treatment incidence was 7.0%. No preterm infant developed stage 4/5 ROP. Mean GA and BW of untreated/treated preterm infants were 28.4/24.6 weeks and 1109/635 g, respectively. Increasing treatment incidence was associated with lower GA, but not with lower BW in logistic regression analysis. In this very immature high-risk cohort, advanced stages 4 and 5 were avoided throughout 9 years of screening. We suggest three factors that contributed to this outcome: (1) strict adherence to current ROP screening and treatment guidelines; (2) prompt and very dense laser coagulation if necessary; and (3) a specialised neonatal intensive care unit with experience of very immature babies.

The life cycle of Huffmanela huffmani Moravec, 1987 (Nematoda: Trichosomoididae), an endemic marine-relict parasite of Centrarchidae from a Central Texas spring

Czech Academy of Sciences Publication Activity Database

Worsham, M.L.D.; Huffman, D. G.; Moravec, František; Gibson, J.R.

2016-01-01

Roč. 63, JUN 10 (2016), č. článku 020. ISSN 1803-6465 Institutional support: RVO:60077344 Keywords : swim bladder nematode * Trichinelloidea * development * intermediate host * Amphipoda * Hyalella * Gammarus * fish * USA Subject RIV: EG - Zoology Impact factor: 1.082, year: 2016

Macrophage Inhibitory Cytokine-1 (MIC-1 as A Biomarker for Diagnosis 
and Prognosis of Stage I-II Non-small Cell Lung Cancer

Directory of Open Access Journals (Sweden)

Yuning LIU

2016-04-01

Full Text Available Background and objective Increased macrophage inhibitory cytokine-1 (MIC-1, member of transforming growth factor-β (TGF-β superfamily, was found in patients serum with epithelial tumors. Therefore, our aim was to delineate the diagnostic and prognostic value of serum MIC-1 in patients with stage I-II non-small cell lung cancer (NSCLC. Methods A total of 152 consecutive patients with stage I–II NSCLC were prospectively enrolled and underwent follow up after total resection of tumor. Serum MIC-1 level was detected in lung cancer patients by ELISA, 48 benign pulmonary disease patients and 105 healthy controls, and was correlated with clinical features and prognosis of patients. Results The level of MIC-1 of NSCLC patients was significantly higher than that of controls (P<0.001 and benign pulmonary disease patients (P<0.001. A threshold of 1,000 pg/mL could be used to diagnose early-stage NSCLC with 70.4% sensitivity and 99.0% specificity. The level of MIC-1 was associated with elder age (P=0.001, female (P=0.03 and T2 (P=0.022. A threshold of 1,465 pg/mL could identify patients with early poor outcome with 72.2% sensitivity and 66.1% specificity. The overall 3-year survival rate in patients with high level of MIC-1 (≥1,465 pg/mL was significantly lower than that of patients with low MIC-1 level (77.6% vs 94.8%. Multivariable Cox regression revealed that a high level of MIC-1 was an independent risk factor for compromised overall survival (HR=3.37, 95%CI: 1.09-10.42, P=0.035. Conclusion High level of serum MIC-1 could be served as a potential biomarker for diagnosis and poorer outcome in patients with early-stage NSCLC.

HER2 and GATA4 are new prognostic factors for early-stage ovarian granulosa cell tumor—a long-term follow-up study

International Nuclear Information System (INIS)

Färkkilä, Anniina; Andersson, Noora; Bützow, Ralf; Leminen, Arto; Heikinheimo, Markku; Anttonen, Mikko; Unkila-Kallio, Leila

2014-01-01

Granulosa cell tumors (GCTs) carry a risk of recurrence also at an early stage, but reliable prognostic factors are lacking. We assessed clinicopathological prognostic factors and the prognostic roles of the human epidermal growth factor receptors (HER 2–4) and the transcription factor GATA4 in GCTs. We conducted a long-term follow-up study of 80 GCT patients with a mean follow-up time of 16.8 years. A tumor-tissue microarray was immunohistochemically stained for HER2–4 and GATA4. Expression of HER2–4 mRNA was studied by means of real time polymerase chain reaction and HER2 gene amplification was analyzed by means of silver in situ hybridization. The results were correlated to clinical data on recurrences and survival. We found that GCTs have an indolent prognosis, with 5-year disease-specific survival (DSS) being 97.5%. Tumor recurrence was detected in 24% of the patients at a median of 7.0 years (range 2.6–18 years) after diagnosis. Tumor stage was not prognostic of disease-free survival (DFS). Of the molecular prognostic factors, high-level expression of HER2, and GATA4, and high nuclear atypia were prognostic of shorter DFS. In multivariate analyses, high-level coexpression of HER2 and GATA4 independently predicted DFS (hazard ratio [HR] 8.75, 95% CI 2.20–39.48, P = 0.002). High-level expression of GATA4 also predicted shorter DSS (HR 3.96, 95% CI 1.45–12.57, P = 0.006). In multivariate analyses, however, tumor stage (II–III) and nuclear atypia were independent prognostic factors of DSS. In conclusion HER2 and GATA4 are new molecular prognostic markers of GCT recurrence, which could be utilized to optimize the management and follow-up of patients with early-stage GCTs

A 4-m evolvable space telescope configured for NASA's HabEx Mission: the initial stage of LUVOIR

Science.gov (United States)

Lillie, Charles F.; MacEwen, Howard A.; Polidan, Ronald S.; Breckinridge, James B.

2017-09-01

Previous papers have described our concept for a large telescope that would be assembled in space in several stages (in different configurations) over a period of fifteen to 20 years. Spreading the telescope development, launch and operations cost over 20 years would minimize the impact on NASA's annual budget and drastically shorten the time between program start and "first light" for this space observatory. The first Stage of this Evolvable Space Telescope (EST) would consist of an instrument module located at the prime focus of three 4-meter hexagonal mirrors arranged in a semi-circle to form one-half of a 12-m segmented mirror. After several years three additional 4-m mirrors would be added to create a 12-m filled aperture. Later, twelve more 4-m mirrors will be added to this Stage 2 telescope to create a 20-m filled aperture space telescope. At each stage the telescope would have an unparalleled capability for UVOIR observations, and the results of these observations will guide the evolution of the telescope and its instruments. In this paper we describe our design concept for an initial configuration of our Evolvable Space Telescope that can meet the requirements of the 4-m version of the HabEx spacecraft currently under consideration by NASA's Habitable Exoplanet Science and Technology Definition Team. This "Stage Zero" configuration will have only one 4-m mirror segment with the same 30-m focal length and a prime focus coronagraph with normal incidence optics to minimize polarization effects. After assembly and checkout in cis-lunar space, the telescope would transfer to a Sun-Earth L2 halo orbit and obtain high sensitivity, high resolution, high contrast UVOIR observations that address the scientific objectives of the Habitable-Exoplanet Imaging Missions.

Colorectal cancer stages transcriptome analysis.

Directory of Open Access Journals (Sweden)

Tianyao Huo

Full Text Available Colorectal cancer (CRC is the third most common cancer and the second leading cause of cancer-related deaths in the United States. The purpose of this study was to evaluate the gene expression differences in different stages of CRC. Gene expression data on 433 CRC patient samples were obtained from The Cancer Genome Atlas (TCGA. Gene expression differences were evaluated across CRC stages using linear regression. Genes with p≤0.001 in expression differences were evaluated further in principal component analysis and genes with p≤0.0001 were evaluated further in gene set enrichment analysis. A total of 377 patients with gene expression data in 20,532 genes were included in the final analysis. The numbers of patients in stage I through IV were 59, 147, 116 and 55, respectively. NEK4 gene, which encodes for NIMA related kinase 4, was differentially expressed across the four stages of CRC. The stage I patients had the highest expression of NEK4 genes, while the stage IV patients had the lowest expressions (p = 9*10-6. Ten other genes (RNF34, HIST3H2BB, NUDT6, LRCh4, GLB1L, HIST2H4A, TMEM79, AMIGO2, C20orf135 and SPSB3 had p value of 0.0001 in the differential expression analysis. Principal component analysis indicated that the patients from the 4 clinical stages do not appear to have distinct gene expression pattern. Network-based and pathway-based gene set enrichment analyses showed that these 11 genes map to multiple pathways such as meiotic synapsis and packaging of telomere ends, etc. Ten of these 11 genes were linked to Gene Ontology terms such as nucleosome, DNA packaging complex and protein-DNA interactions. The protein complex-based gene set analysis showed that four genes were involved in H2AX complex II. This study identified a small number of genes that might be associated with clinical stages of CRC. Our analysis was not able to find a molecular basis for the current clinical staging for CRC based on the gene expression patterns.

Munc18-1-regulated stage-wise SNARE assembly underlying synaptic exocytosis.

Science.gov (United States)

Ma, Lu; Rebane, Aleksander A; Yang, Guangcan; Xi, Zhiqun; Kang, Yuhao; Gao, Ying; Zhang, Yongli

2015-12-23

Synaptic-soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) proteins couple their stage-wise folding/assembly to rapid exocytosis of neurotransmitters in a Munc18-1-dependent manner. The functions of the different assembly stages in exocytosis and the role of Munc18-1 in SNARE assembly are not well understood. Using optical tweezers, we observed four distinct stages of assembly in SNARE N-terminal, middle, C-terminal, and linker domains (or NTD, MD, CTD, and LD, respectively). We found that SNARE layer mutations differentially affect SNARE assembly. Comparison of their effects on SNARE assembly and on exocytosis reveals that NTD and CTD are responsible for vesicle docking and fusion, respectively, whereas MD regulates SNARE assembly and fusion. Munc18-1 initiates SNARE assembly and structures t-SNARE C-terminus independent of syntaxin N-terminal regulatory domain (NRD) and stabilizes the half-zippered SNARE complex dependent upon the NRD. Our observations demonstrate distinct functions of SNARE domains whose assembly is intimately chaperoned by Munc18-1.

Synthesis of N-(5-(Substitutedphenyl-4,5-dihydro-1H-pyrazol-3-yl-4H-1,2,4-triazol-4-amine from 4-Amino-4H-1,2,4-triazole

Directory of Open Access Journals (Sweden)

Ashvin D. Panchal

2011-01-01

Full Text Available N-(4H-1,2,4-Triazol-4-ylacetamide (2 were prepared by reaction of 4-amino-4H-1,2,4-triazole (1 with acetyl chloride in dry benzene. It has been reacted with various aromatic aldehyde to afford 3-(substitutedphenyl-N-(4H-1,2,4-triazol-4-ylacrylamide (3a-e. The synthesis of N-(5-substitutedphenyl-4,5-dihydro-1H-pyrazol-3-yl-4H-1,2,4-triazol-4-amine (4a-e is achieved by the cyclisation of 3a-e with hydrazine hydrate in ethanol. The structures of synthesized compounds were characterized by 1H NMR and IR spectroscopic studies. The purity of the compounds was checked by thin layer chromatography.

Regioselectivity in the Thermal Rearrangement of Unsymmetrical 4-Methyl-4H-1,2,4-triazoles to 1-Methyl-1H-1,2,4-triazoles

Directory of Open Access Journals (Sweden)

Per H.J. Carlsen

2001-11-01

Full Text Available The rearrangement of 4-methyl-3,5-diaryl-4H-1,2,4-triazoles to the corresponding 1-methyl-3,5-diaryl-1H-1,2,4-triazoles showed regioselectivity comparable to that observed for the alkylation of 3,5-diaryl-1H-1,2,4-triazoles. This lends support to a proposed mechanism for the rearrangement that involves consecutive nucleophilic displacements steps.

Evaluation of lymph node numbers for adequate staging of Stage II and III colon cancer

Directory of Open Access Journals (Sweden)

Bumpers Harvey L

2011-05-01

Full Text Available Abstract Background Although evaluation of at least 12 lymph nodes (LNs is recommended as the minimum number of nodes required for accurate staging of colon cancer patients, there is disagreement on what constitutes an adequate identification of such LNs. Methods To evaluate the minimum number of LNs for adequate staging of Stage II and III colon cancer, 490 patients were categorized into groups based on 1-6, 7-11, 12-19, and ≥ 20 LNs collected. Results For patients with Stage II or III disease, examination of 12 LNs was not significantly associated with recurrence or mortality. For Stage II (HR = 0.33; 95% CI, 0.12-0.91, but not for Stage III patients (HR = 1.59; 95% CI, 0.54-4.64, examination of ≥20 LNs was associated with a reduced risk of recurrence within 2 years. However, examination of ≥20 LNs had a 55% (Stage II, HR = 0.45; 95% CI, 0.23-0.87 and a 31% (Stage III, HR = 0.69; 95% CI, 0.38-1.26 decreased risk of mortality, respectively. For each six additional LNs examined from Stage III patients, there was a 19% increased probability of finding a positive LN (parameter estimate = 0.18510, p Conclusions Thus, the 12 LN cut-off point cannot be supported as requisite in determining adequate staging of colon cancer based on current data. However, a minimum of 6 LNs should be examined for adequate staging of Stage II and III colon cancer patients.

Lípidos en el anfípodo Talorchestia margaritae (Amphipoda: Talitridae y su relación con la ecología de la especie

Directory of Open Access Journals (Sweden)

Sandra López

2010-09-01

-5%; Phospholipids: 20-30%; Glycolipids: <1%; sterols: 4%. On the other hand, Triglycerides (TAG were higher in Mangle Quemao, which may be related to the difference between the weights of two locations. The most abundant fatty acid biomarkers in the two studied sites were 16:0 and 18:1(n-9; this last one is characteristic of a carnivorous diet. The other nine markers were identified with changes in their distribution in organisms at Mangle Quemao and between males and females of both populations. Based on observed fatty acids markers we can assume T. margaritae as a generalist carnivore. Those populations were influenced by available food; inducing differences in weight, TAG proportion and markers diversity. Rev. Biol. Trop. 58 (3: 841-855. Epub 2010 September 01.

CT volumetry for gastric carcinoma: association with TNM stage

Energy Technology Data Exchange (ETDEWEB)

Hallinan, James T.P.D.; Peter, Luke; Makmur, Andrew [National University Health System (NUHS), Diagnostic Radiology, Singapore (Singapore); Venkatesh, Sudhakar K. [Mayo Clinic, Department of Radiology, Rochester, MN (United States); Yong, Wei Peng [NUHS, Hematology and Oncology, Singapore (Singapore); So, Jimmy B.Y. [NUHS, Surgery, Singapore (Singapore)

2014-12-15

We evaluated the feasibility of performing CT volumetry of gastric carcinoma (GC) and its correlation with TNM stage. This institutional review board-approved retrospective study was performed on 153 patients who underwent a staging CT study for histologically confirmed GC. CT volumetry was performed by drawing regions of interest including abnormal thickening of the stomach wall. Reproducibility of tumour volume (Tvol) between two readers was assessed. Correlation between Tvol and TNM/peritoneal staging derived from histology/surgical findings was evaluated using ROC analysis and compared with CT evaluation of TNM/peritoneal staging. Tvol was successfully performed in all patients. Reproducibility among readers was excellent (r = 0.97; P = 0.0001). The median Tvol of GC showed an incremental trend with T-stage (T1 = 27 ml; T2 = 32 ml; T3 = 53 ml and T4 = 121 ml, P < 0.01). Tvol predicted with good accuracy T-stage (≥T2:0.95; ≥T3:0.89 and T4:0.83, P = 0.0001), M-stage (0.87, P = 0.0001), peritoneal metastases (0.87, P = 0.0001) and final stage (≥stage 2:0.89; ≥stage 3:0.86 and stage 4:0.87, P = 0.0001), with moderate accuracy for N-stage (≥N1:0.75; ≥N2:0.74 and N3:0.75, P = 0.0001). Tvol was significantly (P < 0.05) more accurate than standard CT staging for prediction of T-stage, N3-stage, M-stage and peritoneal metastases. CT volumetry may provide useful adjunct information for preoperative staging of GC. (orig.)

CT volumetry for gastric carcinoma: association with TNM stage

International Nuclear Information System (INIS)

Hallinan, James T.P.D.; Peter, Luke; Makmur, Andrew; Venkatesh, Sudhakar K.; Yong, Wei Peng; So, Jimmy B.Y.

2014-01-01

We evaluated the feasibility of performing CT volumetry of gastric carcinoma (GC) and its correlation with TNM stage. This institutional review board-approved retrospective study was performed on 153 patients who underwent a staging CT study for histologically confirmed GC. CT volumetry was performed by drawing regions of interest including abnormal thickening of the stomach wall. Reproducibility of tumour volume (Tvol) between two readers was assessed. Correlation between Tvol and TNM/peritoneal staging derived from histology/surgical findings was evaluated using ROC analysis and compared with CT evaluation of TNM/peritoneal staging. Tvol was successfully performed in all patients. Reproducibility among readers was excellent (r = 0.97; P = 0.0001). The median Tvol of GC showed an incremental trend with T-stage (T1 = 27 ml; T2 = 32 ml; T3 = 53 ml and T4 = 121 ml, P < 0.01). Tvol predicted with good accuracy T-stage (≥T2:0.95; ≥T3:0.89 and T4:0.83, P = 0.0001), M-stage (0.87, P = 0.0001), peritoneal metastases (0.87, P = 0.0001) and final stage (≥stage 2:0.89; ≥stage 3:0.86 and stage 4:0.87, P = 0.0001), with moderate accuracy for N-stage (≥N1:0.75; ≥N2:0.74 and N3:0.75, P = 0.0001). Tvol was significantly (P < 0.05) more accurate than standard CT staging for prediction of T-stage, N3-stage, M-stage and peritoneal metastases. CT volumetry may provide useful adjunct information for preoperative staging of GC. (orig.)

Liver fibrosis detection and staging: a comparative study of T1ρ MR imaging and 2D real-time shear-wave elastography.

Science.gov (United States)

Li, Ruo-Kun; Ren, Xin-Pin; Yan, Fu-Hua; Qiang, Jin-Wei; Lin, Hui-Min; Tao Wang; Zhao, Hong-Fei; Chen, Wei-Bo

2017-12-02

To compare the results of T1ρ MR imaging and 2D real-time shear-wave elastography (SWE) for liver fibrosis detection and staging. Twenty-nine rabbit models of CCl 4 -induced liver fibrosis were established and six untreated rabbits served as controls. T1ρ MR imaging and 2D real-time SWE examination were performed at 2, 4, 6, 8, 10, and 12 weeks. T1ρ values and liver stiffness (LS) values were measured. Fibrosis was staged according to the METAVIR scoring system. Correlation test was performed among T1ρ values, LS values, and fibrosis stage. Receiver operating characteristic (ROC) analysis was performed for assessing diagnostic performance of T1ρ and SWE in detection of no fibrosis (F0), substantial fibrosis (≥ F2), severe fibrosis (≥ F3), and cirrhosis (F4). There was moderate positive correlation between fibrosis stage and T1ρ values (r = 0.566; 95% CI 0.291-0.754; P < 0.0001), and LS value (r = 0.726; 95% CI 0.521-0.851; P = 0.003). T1ρ values showed moderate positive correlations with LS values [r = 0.693; 95% confidence interval (CI) 0.472-0.832; P < 0.0001]. Areas Under ROC (AUROCs) were 0.861 (95% CI 0.705-0.953) for SWE and 0.856 (95% CI 0.698-0.950) for T1ρ (P = 0.940), 0.906 (95% CI 0.762-0.978) for SWE and 0.849 (95% CI 0.691-0.946) for T1ρ (P = 0.414), 0.870 (95% CI 0.716-0.958) for SWE and 0.799 (95% CI 0.632-0.913) for T1ρ (P = 0.422), and 0.846 (95% CI 0.687-0.944) for SWE and 0.692 (95% CI 0.517-0.835) for T1ρ (P = 0.137), when diagnosing liver fibrosis with ≥ F1, ≥ F2, ≥ F3, and F4, respectively. There was moderate positive correlation between inflammatory activity and T1ρ values (r = 0.520; 95% CI 0.158-0.807; P = 0.013). T1ρ imaging has potential for liver fibrosis detection and staging with good diagnostic capability similar to that of ultrasonography elastography.

1,3-Di-4-pyridylpropane–4,4′-oxydibenzoic acid (1/1

Directory of Open Access Journals (Sweden)

Hirofumi Hinode

2008-12-01

Full Text Available The hydrothermal reaction of Cd(NO32·4H2O, 1,3-di-4-pyridylpropane (BPP and 4,4′-oxydibenzoic acid (OBA led to the formation of the title compound, C13H14N2·C14H10O5. The asymmetric unit consists of one molecule of OBA and one of BPP. In the OBA molecule, one COOH group is nearly planar with its attached benzene ring [dihedral angle = 0.9 (1°], while the other COOH group is slightly twisted with a dihedral angle of 10.8 (3°. The carboxyl groups form strong intermolecular O—H...N hydrogen bonds with N atoms of the pyridine rings in BPP, linking the molecules into zigzag chains.

Evaluation of 99Tcm-trodat-1 SPECT/CT imaging in the diagnosis of parkinson's disease in early stage

International Nuclear Information System (INIS)

Liu Xiaohua; Tai Jian; Zhang Fuhai; Xiao Qian; Jia Qiang; Dong Feng

2004-01-01

Parkinson's disease is a progressive neurodegenerative disorder characterized by a selective loss of dopamine in the striatum with age. At present, the diagnosis of Parkinson's disease is mainly remained in clinical standard. According to the clinical symptoms and the response to DOPA treatment, it is not difficult to diagnose typical PD. But it is difficult to diagnose early stage PD, which lacks the typical clinical symptoms and signs. A 99Tcm -labeled tropane derivative that binds to dopamine transporter with high selectivity is [2- [ [2- [ [ [3- (4-chlorophenyl)- 8-methyl- 8-azabicyclo [3,2,1 ] oct-2-yl]methyl] (2-mercaptoethyl)amino] eth yl]amino]ethanethiolato(3-)-N2,N2',S2,S2'] oxo-[1R-(exo-exo)] (TRODAT-1). Objective: The purpose of this study is to evaluate the clinical application of 99Tcm-TRODAT-1 SPECT/CT imaging in the diagnosis of Parkinson's disease (PD) in early stage. Methods: Twenty-four patients with early-stage idiopathic Parkinson's disease were recruited. For all patients, the severity was assessed by the Hoehnand Yahrscale. Twenty-four early stage PD patients (15 Hoehn Yahr stage I and 9 Hoehn Yahr stage II), eight advanced PD patients and ten healthy volunteers (five men, five women) were studied by 99Tcm-TRODAT-1 SPECT/CT imaging. 99Tcm-TRODAT-1 was prepared from a lyophilized kit. Brain SPECT imaging was performed 2 hours after injection, using GE Discovery VH equipped with FanBeam collimators. Data were obtained using energy window of 20% centered on 140 KEV for 99Tcm. The brain SPECT data were acquired after Hawkeye CT acquisition. Regions of interest were delineated over the striata and the cerebella, and the ratios of striatum-to-cerebellum (ST/CB) were calculated. Specific uptake in the striatum and its subregions, including the putamen and caudate nucleus, was calculated and compared with that of the other side as well as that of healthy volunteers. Results: Dopamine transporter (DAT) imaging of the 10 healthy volunteers showed

Staging of nasopharyngeal carcinoma investigated by magnetic resonance imaging

International Nuclear Information System (INIS)

Lu Jincheng; Wei Baoqing; Chen Wenzhan; Qian Pudong; Zhang Yiqin; Wei Qing; Cha Wenwu; Li Feng; Ni Ming

2006-01-01

Background and purpose: To investigate the American Joint Commission on Cancer (AJCC) sixth edition staging system of nasopharyngeal carcinoma (NPC) by Magnetic Resonance Imaging (MRI). Patients and methods: One hundred and fifty-nine non-disseminated biopsy-proven NPC patients were studied with MRI before treatment. Retrieval of MRI information enabled us to restage all patients accurately according to the sixth edition of the AJCC staging system. Splitting the respective T and N stages by the significant defining factors identified, the cancer death hazard ratios were modeled by the Cox model in SPSS 10.0 for windows (SPSS Inc, Chicago, IL). Results: Single site of skull base abnormality (HR=3.91, 95% CI: 0.74-20.56) has a superior result to others involved in T3 (HR=5.83, 95% CI: 1.24-27.29). Involvement of either anterior or posterior cranial nerves solely (HR=6.02, 95% CI: 1.55-35.60) was not found to be as a poor prognostic indicator as others involved in T4 (HR=7.81, 95% CI: 1.81-33.63). Less than or equal to 3 cm of N1 (HR=4.01, 95% CI: 0.48-33.83) and N2 (HR=4.72, 95% CI: 0.62-35.78) have a better result than >3 cm of N1 (HR=8.09, 95% CI: 0.95-68.97) and N2 (HR=10.58, 95% CI: 1.32-84.62), respectively. Conclusions: Perhaps, it is better to down-stage single site of skull base abnormality from T3 to T2, and involvement of either anterior or posterior cranial nerves solely from T4 to T3, meanwhile, ≤3 cm of N2 down-stage to N1, >3 cm of N1 up-stage to N2

LEF-1 and TCF4 expression correlate inversely with survival in colorectal cancer

Directory of Open Access Journals (Sweden)

Kirchner Thomas

2010-11-01

Full Text Available Abstract Background Most colorectal carcinomas are driven by an activation of the canonical Wnt signalling pathway, which promotes the expression of multiple target genes mediating proliferation inavasion and invasion. Upon activation of the Wnt signalling pathway its key player β-catenin translocates from the cytoplasm to the nucleus and binds to members of the T-cell factor (TCF/lymphoid enhancer factor (LEF-1 family namely LEF-1 and TCF4 which are central mediators of transcription. In this study we investigated the expression of β-Catenin, LEF1 and TCF4 in colorectal carcinomas and their prognostic significance. Methods Immunohistochemical analyses of LEF-1, TCF4 and nuclear β-Catenin were done using a tissue microarray with 214 colorectal cancer specimens. The expression patterns were compared with each other and the results were correlated with clinicopathologic variables and overall survival in univariate and multivariate analysis. Results LEF-1 expression was found in 56 (26% and TCF4 expression in 99 (46% of colorectal carcinomas and both were heterogenously distributed throughout the tumours. Comparing LEF-1, TCF4 and β-catenin expression patterns we found no correlation. In univariate analysis, TCF4 expression turned out to be a negative prognostic factor being associated with shorter overall survival (p = 0.020, whereas LEF-1 expression as well as a LEF-1/TCF4 ratio were positive prognostic factors and correlated with longer overall survival (p = 0.015 respectively p = 0.001. In multivariate analysis, LEF-1 and TCF4 expression were confirmed to be independent predictors of longer respectively shorter overall survival, when considered together with tumour stage, gender and age (risk ratio for LEF-1: 2.66; p = 0.027 risk ratio for TCF4: 2.18; p = 0.014. Conclusions This study demonstrates different prognostic values of LEF-1 and TCF4 expression in colorectal cancer patients indicating different regulation of these transcription

Sleep-stage transitions during polysomnographic recordings as diagnostic features of type 1 narcolepsy

DEFF Research Database (Denmark)

Christensen, Julie Anja Engelhard; Carrillo, Oscar; Leary, Eileen B.

2015-01-01

Objective: Type 1 narcolepsy/hypocretin deficiency is characterized by excessive daytime sleepiness, sleep fragmentation, and cataplexy. Short rapid eye movement (REM) latency (≤15 min) during nocturnal polysomnography (PSG) or during naps of the multiple sleep latency test (MSLT) defines a sleep......-onset REM sleep period (SOREMP), a diagnostic hallmark. We hypothesized that abnormal sleep transitions other than SOREMPs can be identified in type 1 narcolepsy. Methods: Sleep-stage transitions (one to 10 epochs to one to five epochs of any other stage) and bout length features (one to 10 epochs) were...... of 19 cases and 708 sleep-clinic patients was used for the validation. Results: (1) ≥5 transitions from ≥5 epochs of stage N1 or W to ≥2 epochs of REM sleep, (2) ≥22 transitions from ≥3 epochs of stage N2 or N3 to ≥2 epochs of N1 or W, and (3) ≥16 bouts of ≥6 epochs of N1 or W were found to be highly...

CT staging of renal pelvis tumor

International Nuclear Information System (INIS)

Yoon, Soo Woong; Cho, Kyoung Sik; Lee, Jong Hwa; Ham, Su Yeon; Won, Yeong Cheol; Ji, Eun Kyung; Choi, Seong Hun; Shin, Byung Suck

1999-01-01

To assess the value of computed tomography (CT) in the preoperative staging of transitional cell carcinoma (TCC) of the renal pelvis. We retrospectively evaluated the CT TNM staging of 38 patients with TCC of the renal pelvis who had undergone preoperative abdominal CT examination between January 1990 and January 1998. In CT staging for differentiation between early-stage (T0-2) and advanced-stage disease (T3-T4), three criteria were used, namely the presence or obliteration of the renal sinus fat layer, the smoothness or irregularity of margin between the tumor and renal parenchyma, and the presence or absence of hydronephrosis proximal to the tumor. CT staging was performed by two genitourinary radiologists blinded to the pathologic results, and was compared with pathologic staging. Pathologic results revealed 19 cases of early stage disease (T0=8, T1=9, T2=2) and 19 of advanced stage (T3=12, T4=7). Overall CT staging accuracy was 82%(31/38) ; four cases were overstaged and three were understaged. In early-stage disease, sensitivity and specificity were 79%, and 84%, and in advanced stage disease were 83% and 80%. Three of four overstaged cases showed hydronephrosis proximal to the tumor. In the second CT staging, using proximal hydronephrosis of the tumor as a criterion for early-stage disease, the sensitivity and specificity of early-stage disease were 95% and 75%, respectively, and the specificity of advanced-stage disease was 95%. When hydronephrosis proximal to a tumor was considered to be a sign of early stage disease, the CT staging of renal pelvic TCC was highly accurate

Results of an Advanced Fan Stage Operating Over a Wide Range of Speed and Bypass Ratio. Part 1; Fan Stage Design and Experimental Results

Science.gov (United States)

Suder, Kenneth L.; Prahst, Patricia S.; Thorp, Scott A.

2011-01-01

NASA s Fundamental Aeronautics Program is investigating turbine-based combined cycle (TBCC) propulsion systems for access to space because it provides the potential for aircraft-like, space-launch operations that may significantly reduce launch costs and improve safety. To this end, National Aeronautics and Space Administration (NASA) and General Electric (GE) teamed to design a Mach 4 variable cycle turbofan/ramjet engine for access to space. To enable the wide operating range of a Mach 4+ variable cycle turbofan ramjet required the development of a unique fan stage design capable of multi-point operation to accommodate variations in bypass ratio (10 ), fan speed (7 ), inlet mass flow (3.5 ), inlet pressure (8 ), and inlet temperature (3 ). In this paper, NASA has set out to characterize a TBCC engine fan stage aerodynamic performance and stability limits over a wide operating range including power-on and hypersonic-unique "windmill" operation. Herein, we will present the fan stage design, and the experimental test results of the fan stage operating from 15 to 100 percent corrected design speed. Whereas, in the companion paper, we will provide an assessment of NASA s APNASA code s ability to predict the fan stage performance and operability over a wide range of speed and bypass ratio.

Synthesis of diadenosine 5', 5'''-P1, P4-tetraphosphate (AP4A) in sea urchin embryos

International Nuclear Information System (INIS)

Morioka, Mizue; Shimada, Hiraku

1984-01-01

Sea urchin embryos were labeled with ( 3 H)adenosine at two developmental stages (morula and prism) and the labeled acid-soluble nucleotides were fractionated successively by column chromatography with DEAE-Sephadex and DEAE-cellulose, and by thin-layer chromatography on a PEI-cellulose plate. Significant radioactivity was detected on the PEI-cellulose plate at the region of diadenosine 5', 5'''-P 1 , P 4 -tetraphosphate (AP 4 A). After treatment of this fraction with phosphodiesterase, the radioactivity was all recovered in the AMP region, while alkaline phosphatase had no effect on the AP 4 A fraction. The present result suggests that AP 4 A is actively synthesized in the sea urchin embryos. (author)

THE STAGES OF HETEROTIC HYBRIDS F1 DEVELOPMENT IN EUROPEAN RADISH

Directory of Open Access Journals (Sweden)

M. A. Kosenko

2017-01-01

Full Text Available The scheme  of  development  of  two-line  of  hybrids  F1  in European radish based on self-incompatibility includes five stages, as follows: 1 – selection of self-incompatible lines, common and specified combining ability estimation; 2 – inbreeding and selection to make the lines homozygous for morphological traits, common and specified combining ability estimation; maintenance and reproduction of self-incompatible lines; 4 – production of hybrid seeds. The research work on assessment of hybrid F1 that were obtained from cross of eight self-incompatible lines of European winter radish by the Griffing’s method was carried out in 2016. The assessment of length, diameter and yield of radish root was performed. According to the root shape the heterotic hybrids F1 were divided into three groups: rounded-flat,  48.2%; round, 50.0%; and flatten-round,  1.8%. The level of root marketability of hybrids F1 reached 100%. As a result of the work the promising hybrid combination distinguished by high uniformity, marketability and high yield were selected out.

Thermal decomposition of rhenium (5) complexes with 1,2,4-triazole. Termicheskoe razlozhenie kompleksov reniya (5) s 1,2,4-triazolom

Energy Technology Data Exchange (ETDEWEB)

Amindzhanov, A A; Gagieva, S Ch; Kotegov, K V [Tadzhikskij Gosudarstvennyj Univ., Dushanbe (Tajikistan)

1991-01-01

Processes of thermal decomposition of rhenium (5) complexes with 1,2,4-triazole were studied. Thermolysis products were identified on the basis of data of the element analysis, IR spectra, conductometry and other methods. It is ascertained that at the first stage of thermolysis of hydroxyl-containing monomer complexes removal of water molecules occurs, and at the second one - dimerization process with formation of Re-O-Re group. It is shown that the nature of halide ion practically does not affect the temperature of the start of intensive thermal decomposition of the complexes.

Coordinates for a High Performance 4:1 Pressure Ratio Centrifugal Compressor

Science.gov (United States)

McKain, Ted F.; Holbrook, Greg J.

1997-01-01

The objective of this program was to define the aerodynamic design and manufacturing coordinates for an advanced 4:1 pressure ratio, single stage centrifugal compressor at a 10 lbm/sec flow size. The approach taken was to perform an exact scale of an existing DDA compressor originally designed at a flow size of 3.655 lbm/sec.

Neuroblastoma mRNAs predict outcome in children with stage 4 neuroblastoma: a European HR-NBL1/SIOPEN study.

Science.gov (United States)

Viprey, Virginie F; Gregory, Walter M; Corrias, Maria V; Tchirkov, Andrei; Swerts, Katrien; Vicha, Ales; Dallorso, Sandro; Brock, Penelope; Luksch, Roberto; Valteau-Couanet, Dominique; Papadakis, Vassilios; Laureys, Genevieve; Pearson, Andrew D; Ladenstein, Ruth; Burchill, Susan A

2014-04-01

To evaluate the hypothesis that detection of neuroblastoma mRNAs by reverse transcriptase quantitative polymerase chain reaction (RTqPCR) in peripheral blood (PB) and bone marrow aspirates (BM) from children with stage 4 neuroblastoma are clinically useful biomarkers of risk. RTqPCR for paired-like homeobox 2b (PHOX2B), tyrosine hydroxylase (TH), and doublecortin (DCX) mRNA in PB and BM of children enrolled onto the High-Risk Neuroblastoma Trial-1 of the European Society of Pediatric Oncology Neuroblastoma Group (HR-NBL1/SIOPEN) was performed at diagnosis and after induction therapy. High levels of TH, PHOX2B, or DCX mRNA in PB or BM at diagnosis strongly predicted for worse event-free survival (EFS) and overall survival (OS) in a cohort of 290 children. After induction therapy, high levels of these mRNAs predicted worse EFS and OS in BM but not in PB. Combinations of mRNAs in BM did not add to the predictive power of any single mRNA. However, in the original (n = 182) and validation (n = 137) PB cohorts, high TH (log10TH > 0.8) or high PHOX2B (log10PHOX2B > 0.28) identify 19% of children as ultrahigh risk, with 5-year EFS and OS rates of 0%; OS rate was 25% (95% CI, 16% to 36%) and EFS rate was 38% (95% CI, 28% to 49%) in the remaining children. The magnitude of reduction in mRNA level between diagnosis and postinduction therapy in BM or PB was not of additional predictive value. High levels of TH and PHOX2B mRNA in PB at diagnosis objectively identify children with ultrahigh-risk disease who may benefit from novel treatment approaches. The level of TH, PHOX2B, and DCX mRNA in BM and/or PB at diagnosis might contribute to an algorithm to improve stratification of children for treatment.

Synthesis, characterization, thermal properties and theoretical investigation on Bis(guanidinium) 4,4‧- Azo-1H-1,2,4-triazol-5-one

Science.gov (United States)

Cao, Wen-li; Guo, Jia-jia; Chen, Xiang; Ding, Zi-mei; Xu, Kang-zhen; Song, Ji-rong; Fan, An; Huang, Jie

2017-11-01

Bis(guanidinium) 4,4‧-Azo-1H-1,2,4-triazol-5-one [G2(ZTO)] was synthesized and characterized by X-ray single crystal diffraction, elemental analyzer and Fourier Transform Infrared (FT-IR) spectrometer. The result from X-ray single crystal diffraction indicates that G2(ZTO) crystallizes in the monoclinic space group P2(1)/c with parameters of a = 4.779(2) Å, b = 9.081(4) Å, c = 14.676(6) Å, α = 90.00°, β = 92.43(7)°, γ = 90.00°, V = 636.4(5) Å3, Z = 2, μ(Mo Kα) = 0.131, F(000) = 328, S = 1.071, Dc = 1.640 g·cm-3, R1 = 0.0510 and wR2 = 0.1389. Interestingly enough, its structure does not contain crystallization water, which is a unique characteristic in this material. Besides, the molecular geometry of the compound was optimized by using Density Functional Theory (DFT) method at B3LYP/6-31G (d, p) level in the ground state, revealing that the obtained geometric parameters are in accordance with the X-ray result of the structure. The experimental vibrational spectrum was compared with the calculated spectrum. Besides, molecular electrostatic potential (MEP) of G2(ZTO) was computed with the same method in gas phase, theoretically. The thermal properties of this compound were investigated by DSC, TG/DTG and micro-DSC methods. The results manifest that its thermal behavior can be divided into two main decomposition stages, the first intense decomposition peak temperature is 248.11 °C at the heating rate of 10 °C·min-1, which is higher than that of RDX (219 °C) but slightly lower than that of G(ZTO)·H2O (252.08 °C). The constant-volume combustion heat (ΔcU) of G2(ZTO), G(ZTO)·H2O and ZTO were determined and then the enthalpy of formation were calculated. The results show that G2(ZTO) possesses the highest standard molar enthalpy of formation, which may be explained by the fact that G2(ZTO) contains no water and possesses the highest nitrogen content in all guanidine salts. Moreover, the apparent activation energy (E), thermal stability and safety

Treatment of Early-Stage Unfavorable Hodgkin Lymphoma: Efficacy and Toxicity of 4 Versus 6 Cycles of ABVD Chemotherapy With Radiation

Energy Technology Data Exchange (ETDEWEB)

Gunther, Jillian R. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Fanale, Michelle A. [Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Reddy, Jay P. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Akhtari, Mani [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Department of Radiation Oncology, The University of Texas Medical Branch at Galveston, Galveston, Texas (United States); Smith, Grace L.; Pinnix, Chelsea C.; Milgrom, Sarah A.; Yehia, Zeinab Abou; Allen, Pamela K.; Osborne, Eleanor M. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mawlawi, Osama [Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Dabaja, Bouthaina S., E-mail: bdabaja@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

2016-09-01

Purpose: The German Hodgkin Study Group HD11 trial validated 4 cycles of doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy followed by involved field radiation therapy (IFRT) for early unfavorable Hodgkin lymphoma (HL) patients. However, practitioners often recommend 6 cycles followed by RT, especially for bulky disease. We compared patient outcomes after treatment with 4 or 6 cycles of ABVD followed by RT (IFRT and involved site RT [ISRT]). Methods and Materials: We identified 128 patients treated for early unfavorable HL (GHSG criteria) between 2000 and 2013. Clinical outcomes (overall survival [OS] and freedom from relapse [FFR]) were estimated using Kaplan-Meier analysis. Toxicities were evaluated. Results: The median follow-up time was 5.0 years. Patients received 4 (70 patients, 55%) or 6 (58 patients, 45%) cycles of chemotherapy. Bulky disease was present in 22 patients (31%; 0 stage IA, 3 stage IB, 19 stage IIA) of the 4-cycle group and 42 patients (72%; 5 stage IA, 3 stage IB, 34 stage IIA) of the 6-cycle group. For patients receiving 4 and 6 cycles, the 6-year OS was 100% and 97% (P=.35), respectively, and the 6 year FFR was 100% and 98% (P=.28), respectively. More patients received 6 cycles if they were treated before 2010 (HD11 report) (P=.01) and if they had bulky disease (P<.01). Sixty-eight percent of patients received ISRT. The 6-year FFR was 99% and 100% for patients receiving ISRT and IFRT, respectively (P=.58). More patients experienced bleomycin pulmonary toxicity in the 6-cycle group (20% vs 31%, P=.16). For patients with bulky disease, the 4-year FFR was similar with receipt of 4 (100%) or 6 (98%) cycles (P=.48) and IFRT (100%) or ISRT (98%) (P=.52). There were no deaths among patients with bulky disease. Conclusions: Patients with early unfavorable HL have excellent outcomes with 4 cycles of ABVD chemotherapy followed by ISRT. Six cycles of chemotherapy does not appear superior for disease control, even for bulky disease.

Treatment of Early-Stage Unfavorable Hodgkin Lymphoma: Efficacy and Toxicity of 4 Versus 6 Cycles of ABVD Chemotherapy With Radiation

International Nuclear Information System (INIS)

Gunther, Jillian R.; Fanale, Michelle A.; Reddy, Jay P.; Akhtari, Mani; Smith, Grace L.; Pinnix, Chelsea C.; Milgrom, Sarah A.; Yehia, Zeinab Abou; Allen, Pamela K.; Osborne, Eleanor M.; Mawlawi, Osama; Dabaja, Bouthaina S.

2016-01-01

Purpose: The German Hodgkin Study Group HD11 trial validated 4 cycles of doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy followed by involved field radiation therapy (IFRT) for early unfavorable Hodgkin lymphoma (HL) patients. However, practitioners often recommend 6 cycles followed by RT, especially for bulky disease. We compared patient outcomes after treatment with 4 or 6 cycles of ABVD followed by RT (IFRT and involved site RT [ISRT]). Methods and Materials: We identified 128 patients treated for early unfavorable HL (GHSG criteria) between 2000 and 2013. Clinical outcomes (overall survival [OS] and freedom from relapse [FFR]) were estimated using Kaplan-Meier analysis. Toxicities were evaluated. Results: The median follow-up time was 5.0 years. Patients received 4 (70 patients, 55%) or 6 (58 patients, 45%) cycles of chemotherapy. Bulky disease was present in 22 patients (31%; 0 stage IA, 3 stage IB, 19 stage IIA) of the 4-cycle group and 42 patients (72%; 5 stage IA, 3 stage IB, 34 stage IIA) of the 6-cycle group. For patients receiving 4 and 6 cycles, the 6-year OS was 100% and 97% (P=.35), respectively, and the 6 year FFR was 100% and 98% (P=.28), respectively. More patients received 6 cycles if they were treated before 2010 (HD11 report) (P=.01) and if they had bulky disease (P<.01). Sixty-eight percent of patients received ISRT. The 6-year FFR was 99% and 100% for patients receiving ISRT and IFRT, respectively (P=.58). More patients experienced bleomycin pulmonary toxicity in the 6-cycle group (20% vs 31%, P=.16). For patients with bulky disease, the 4-year FFR was similar with receipt of 4 (100%) or 6 (98%) cycles (P=.48) and IFRT (100%) or ISRT (98%) (P=.52). There were no deaths among patients with bulky disease. Conclusions: Patients with early unfavorable HL have excellent outcomes with 4 cycles of ABVD chemotherapy followed by ISRT. Six cycles of chemotherapy does not appear superior for disease control, even for bulky disease.

beta. -1,4-glucan occurring in homogenate of Phaseolus aureus seedlings. Possible nascent stage of cellulose biosynthesis in vivo

Energy Technology Data Exchange (ETDEWEB)

Satoh, S; Matsuda, K; Tamari, K

1976-12-01

A small amount of cytoplasmic ..beta..-1,4-glucan, which might be involved in the synthesis of cellulose in the cell wall, was found in the homogenate prepared from the hypocotyls of seedlings of Phaseolus aureus. Upon hydrolysis by cellulase of the 20,000xg pellet from the cytoplasmic fraction of segments incubated in a (/sup 14/C)-glucose solution, (/sup 14/C)-cellobiose was produced, with specific radioactivities 3 to 10 times greater than those of the cellobiose from cellulose in the cell wall at various incubation periods. The incoporation of radioactivity from (/sup 14/C)-glucose into this cytoplasmic ..beta..-1,4-glucan was therefore faster than that into cellulose constituting the cell wall. Hence, it seemed that the former ..beta..-1,4-glucan could be turned over. To examine whether the cytoplasmic ..beta..-1,4-glucan is carried by some subcellular components, cytoplasmic ..beta..-1,4-glucan in the cell was fractionated by differential centrifugation, two enzyme activities being measured as the markers of subcellular components. The distribution of ..beta..-1,4-glucan was similar to that of UDPG-glucosyl-transferase activity but not to that of IDP-ase activity. The result suggests that the cytoplasmic ..beta..-1,4-glucan has some relation to plasma membranes. Coumarin, known as a specific inhibitor for the biosynthesis of cellulose in plant cells, was shown to inhibit the incorporation of radio-carbon from (/sup 14/C)-glucose into cytoplasmic ..beta..-1,4-glucan to the same extent as that into cellulose in the cell wall of the hypocotyls.

CD4 T cells remain the major source of HIV-1 during end stage disease.

NARCIS (Netherlands)

M.E. van der Ende (Marchina); M. Schutten (Martin); B. Raschdorff; G. Grosschupff; P. Racz; A.D.M.E. Osterhaus (Albert); K. Tenner-Racz

1999-01-01

textabstractOBJECTIVE: To assess the source of HIV-1 production in lymphoid tissue biopsies from HIV-infected patients, with no prior anti-retroviral protease inhibitor treatment, with a CD4 cell count > 150 x 10(6)/l (group I) or < 50 x 10(6)/l (group II), co-infected with Mycobacterium

Chronic infections in hip arthroplasties: comparing risk of reinfection following one-stage and two-stage revision: a systematic review and meta-analysis

Directory of Open Access Journals (Sweden)

Lange J

2012-03-01

Full Text Available Jeppe Lange1,2, Anders Troelsen3, Reimar W Thomsen4, Kjeld Søballe1,51Lundbeck Foundation Centre for Fast-Track Hip and Knee Surgery, Aarhus C, 2Center for Planned Surgery, Silkeborg Regional Hospital, Silkeborg, 3Department of Orthopaedics, Hvidovre Hospital, Hvidovre, 4Department of Clinical Epidemiology, Aarhus University Hospital, Aalborg, 5Department of Orthopaedics, Aarhus University Hospital, Aarhus C, DenmarkBackground: Two-stage revision is regarded by many as the best treatment of chronic infection in hip arthroplasties. Some international reports, however, have advocated one-stage revision. No systematic review or meta-analysis has ever compared the risk of reinfection following one-stage and two-stage revisions for chronic infection in hip arthroplasties.Methods: The review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. Relevant studies were identified using PubMed and Embase. We assessed studies that included patients with a chronic infection of a hip arthroplasty treated with either one-stage or two-stage revision and with available data on occurrence of reinfections. We performed a meta-analysis estimating absolute risk of reinfection using a random-effects model.Results: We identified 36 studies eligible for inclusion. None were randomized controlled trials or comparative studies. The patients in these studies had received either one-stage revision (n = 375 or two-stage revision (n = 929. Reinfection occurred with an estimated absolute risk of 13.1% (95% confidence interval: 10.0%–17.1% in the one-stage cohort and 10.4% (95% confidence interval: 8.5%–12.7% in the two-stage cohort. The methodological quality of most included studies was considered low, with insufficient data to evaluate confounding factors.Conclusions: Our results may indicate three additional reinfections per 100 reimplanted patients when performing a one-stage versus two-stage revision. However, the

Hyperfractionated radiotherapy (2100 cGY) for stage 4 neuroblastoma as part of intensive multimodality therapy

International Nuclear Information System (INIS)

Gollamudi, S.V.; Kushner, B.H.; Merchant, T.E.; LaQuaglia, M.; Lindsley, K.; Rosenfield, N.; Abramson, S.; Kramer, K.; Cheung, N.K.V.

1997-01-01

PURPOSE: To retrospectively evaluate the role of hyperfractionated radiotherapy to the primary site following induction chemotherapy and aggressive surgical resection in patients (pts) with stage 4 neuroblastoma. MATERIALS AND METHODS: 48 previously untreated children (median age at diagnosis 3 yo, range 1-10 yo) with stage 4 neuroblastoma achieved a complete-, near-complete-, or partial-remission after multimodality therapy (protocol N4: 6 pts, N5: 7 pts, N6: 27 pts, or N7: 8 pts). All protocols included a regimen consisting of dose-intensive multiagent chemotherapy, maximal surgical debulking, followed by hyperfractionated radiotherapy. Most pts then underwent consolidation with either autologous marrow transplantation (N4 and N5), or immunotherapy (N6 and N7) with radioimmunotherapy (N7). Of 48 pts, 46 had microscopic disease at the primary site prior to beginning radiotherapy (45 underwent gross total resection of the primary, and one had no residual primary disease after chemotherapy alone). One pt had a partial resection, and one remained unresectable after mutimodality therapy. The pre-chemotherapy volume of the primary tumor and regional lymph nodes were irradiated to a total dose of 2100cGy delivered twice-daily in 150 cGy fractions over 7 treatment days. RESULTS: With a median follow-up of 32.5 months (range= 8-145 months), local-regional control was achieved in 44 of the 48 pts. Of the pts who are progression-free, median follow-up was 53.5 months. Overall, 24 of 48 pts progressed, three with local-regional recurrence as the first site of relapse, one with distant failure first and subsequent local-regional recurrence, and 21 with distant failure only. The probability of local-regional control at 32 months was 83%. One of the four pts with local-regional relapse never achieved a complete remission with either systemic therapy, surgical resection or radiotherapy. The progression-free survival at 32 months was 46%. Median time to overall progression was 16

Post orchiectomy management in stage II testicular seminoma

International Nuclear Information System (INIS)

Singhal, S.; Dixit, S.; Ramana Murthy, R.; Neema, J.P.; Vyas, R.K.; Baboo, H.A.

1994-01-01

Twenty eight patients with stage II A and twenty patients with stage II B testicular seminoma were treated at this institute between January 1982 and December 1988. The three year crude survival observed in this retrospective analysis was 82% and 75% respectively. Post orchiectomy infradiaphragmatic radiotherapy was the mainstay of the treatment. In stage II A, 4 patients were administered adjuvant chemotherapy as well. Prophylactic mediastinal irradiation (PMI) was not employed as a routine in this subgroup. Eight patients (28%) relapsed (mediastinal nodes - 4, pulmonary - 3, scrotal - 1). In stage II B, twelve patients were treated with primary abdominal radiotherapy and of them 4 were delivered PMI as well. Induction chemotherapy was administered in remaining 8 patients. Seven patients (35%) relapsed (pulmonary-4, mediastinal nodes-3). Mediastinal recurrence was noted only in those who were treated with abdominal radiotherapy alone. Though salvage chemotherapy proved successful in 5 of the seven patients (70%) with nodal relapse, none of the patients with extranodal relapse responded to subsequent chemotherapy. For stage II A abdominal radiotherapy alone is recommended and for stage II B induction chemotherapy is advised keeping radiotherapy reserved for residual mass. PMI as a routine in stage II testicular seminoma is not advocated as no survival benefit is observed. (author) 15 refs., 6 tabs

Analyzing proteasomal subunit expression reveals Rpt4 as a prognostic marker in stage II colorectal cancer.

LENUS (Irish Health Repository)

2012-02-01

Colorectal cancer is a leading cause of cancer-related deaths worldwide. Early diagnosis and treatment of colorectal cancer is the key to improving survival rates and as such a need exists to identify patients who may benefit from adjuvant chemotherapy. The dysregulation of the ubiquitin-proteasome system (UPS) has been implicated in oncogenesis and cancer cell survival, and proteasome inhibitors are in clinical use for a number of malignancies including multiple myeloma. In our study, we examined the protein expression of several key components of the UPS in colorectal cancer using immunohistochemistry to determine expression levels of ubiquitinylated proteins and the proteasomal subunits, 20S core and Rpt4 in a cohort of 228 patients with colon cancer. Multivariate Cox analysis revealed that neither the intensity of either ubiquitinylated proteins or the 20S core was predictive in either Stage II or III colon cancer for disease free survival or overall survival. In contrast, in Stage II patients increased Rpt4 staining was significantly associated with disease free survival (Cox proportional hazard ratio 0.605; p = 0.0217). Our data suggest that Rpt4 is an independent prognostic variable for Stage II colorectal cancer and may aid in the decision of which patients undergo adjuvant chemotherapy.

Correlation of endothelin-1 concentration and angiotensin-converting enzyme activity with the staging of liver fibrosis.

Science.gov (United States)

Kardum, Dusko; Fabijanić, Damir; Lukić, Anita; Romić, Zeljko; Petrovecki, Mladen; Bogdanović, Zoran; Jurić, Klara; Urek-Crncević, Marija; Banić, Marko

2012-06-01

Increased serum angiotensin-converting enzyme (SACE) activity and serum concentration of endothelin-1 (ET-1) were found in liver cirrhosis. We investigated a correlation between the different stages of liver fibrosis and SACE activity and serum ET-1 concentration. Seventy patients with pathohistologically established chronic liver disease were divided in three groups according to Ishak criteria for liver fibrosis: minimal fibrosis (Ishak score 0-1, n =20), medium fibrosis (Ishak score 2-5, n=20) and cirrhosis (Ishak score 6, n=30). SACE activity and ET-1 concentration were determined using commercial ELISA kits. SACE activity and ET-1 concentrations were proportional to the severity of disease, the highest being in patients with liver cirrhosis. Maximal increase in SACE activity was found between minimal and medium fibrosis while maximal increase in ET-1 concentration was revealed between medium fibrosis and cirrhosis. The analysis of the Receiver Operating Characteristic (ROC) curve for SACE activity suggested a cut-off value to separate minimal from medium fibrosis at 59.00 U/L (sensitivity 100%, specificity 64.7%). The cut-off value for serum ET-1 concentration to separate medium fibrosis from cirrhosis was 12.4 pg/mL (sensitivity 96.8%, specificity 94.4%). A positive correlation between SACE activity and ET-1 concentration was registered (Spearman's ñ = 0.438, p = 0.004). Both SACE activity and ET-1 concentration were increased in all stages of liver fibrosis. Cut-off points for SACE activity and ET-1 concentration could be a biochemical marker for the progression of fibrosis. Positive correlation between SACE activity and ET-1 concentration might indicate their interaction in the development of liver cirrhosis.

ranibizumab in the management of advanced Coats disease Stages 3B and 4: long-term outcomes.

Science.gov (United States)

Gaillard, Marie-Claire; Mataftsi, Assimina; Balmer, Aubin; Houghton, Susan; Munier, Francis L

2014-11-01

Laser photocoagulation and cryotherapy to completely destroy telangiectatic vessels and ischemic retina in Coats disease is barely applicable in advanced cases with total retinal detachment, and globe survival is notoriously poor in Stages 3B and 4. Anti-vascular endothelial growth factor intravitreal injections may offer new prospects for these patients. This study is a retrospective review of all consecutive patients with Coats disease treated with neoadjuvant or adjuvant intravitreal ranibizumab plus conventional and amblyopia treatment as appropriate. Nine patients (median age, 13 months) presenting Coats Stages 3B and 4 (5 and 4 eyes, respectively) were included. Iris neovascularization resolved within 2 weeks and retinal reapplication within 4 months in all patients. At last follow-up, globe survival was 100% with anatomical success in 8 of the 9 eyes. With a median follow-up of 50 months, fibrotic vitreoretinopathy was developed in 5 of the 9 cases, one leading to tractional retinal detachment and ultimately phthisis bulbi. The remaining 4 of the 9 eyes achieved some vision (range, 0.02-0.063). To the best of the authors' knowledge, this is the largest reported series of late-stage Coats undergoing anti-vascular endothelial growth factor therapy, a homogenous cohort of patients treated with a single agent and with the longest follow-up. This study supports the role of ranibizumab in advanced disease by transient restoration of the hemato-retinal barrier and suppression of neovascularization to facilitate classic treatment. At the last follow-up, the authors report unprecedented anatomical success and functional outcome.

Cephalometric evaluation of the effects of the Twin Block appliance in subjects with Class II, Division 1 malocclusion amongst different cervical vertebral maturation stages

Directory of Open Access Journals (Sweden)

Aisha Khoja

Full Text Available ABSTRACT Objectives: To evaluate the cephalometric changes in skeletal, dentoalveolar and soft tissue variables induced by Clark's Twin Block (CTB in Class II, Division 1 malocclusion patients and to compare these changes in different cervical vertebral maturation stages. Methods: Pre- and post-treatment/observation lateral cephalograms of 53 Class II, Division 1 malocclusion patients and 60 controls were compared to evaluate skeletal, dentoalveolar and soft tissue changes. Skeletal maturity was assessed according to cervical vertebral maturation stages. Pre- and post-treatment/observation mean changes and differences (T2-T1 were compared by means of Wilcoxon sign rank and Mann-Whitney U-tests, respectively. Intergroup comparisons between different cervical stages were performed by means of Kruskal-Wallis test and Mann-Whitney U-test (p ≤ 0.05 . Results: When compared with controls, there was a significant reduction in ANB angle (p < 0.001, which was due to a change in SNB angle in CS-2 and CS-3 (p < 0.001, and in SNA (p < 0.001 and SNB (p = 0.016 angles in the CS-4 group. There was significant increase in the GoGn-SN angle in CS-2 (p = 0.007 and CS-4 (p = 0.024, and increase in Co-Gn and Go-Gn amongst all cervical stages (p < 0.05. There was significant decrease in U1-SN and increase in IMPA amongst all cervical stages (p < 0.05. There was significant retraction of the upper lip in CS-3 (p = 0.001, protrusion of the lower lip in CS-2 (p = 0.005, increase in nasolabial angle in CS-4 (p = 0.006 and Z-angle in CS-3 (p = 0.016, reduction in H-angle in CS-2 (p = 0.013 and CS-3 (p = 0.002 groups. When pre- and post-treatment mean differences were compared between different cervical stages, significant differences were found for SNA, SNB and UI-SN angles and overjet. . Conclusions: The Twin-Block along with the normal craniofacial growth improves facial esthetics in Class II, Division 1 malocclusion by changes in underlying skeletal and

The effects of EGF and IGF-1 on FSH-mediated in vitro maturation of domestic cat oocytes derived from follicular and luteal stages.

Science.gov (United States)

Yıldırım, Koray; Vural, M Rıfat; Küplülü, Sükrü; Ozcan, Ziya; Polat, I Mert

2014-04-01

The objective of this study was to evaluate the influence of epidermal growth factor (EGF) and insulin like growth factor-I (IGF-1) on the in vitro maturation of cat oocytes recovered from follicular and luteal stage ovaries. Oocytes from follicular (n=580) and luteal (n=209) stages were harvested and divided into four groups, which were cultured in FSH-mediated maturation medium supplemented with: (1) EGF alone (25ng/mL); (2) IGF-1 alone (100ng/mL); (3) EGF+IGF-1 (25ng/mL EGF+100ng/mL IGF-I); or (4) no growth factor (control). The proportion of follicular stage oocytes reaching the metaphase II stage was significantly higher than that of oocytes obtained at the luteal stage in both control and study groups (pIGF-1, and 78.1% in EGF+IGF-1 groups, whereas the respective values for gametes collected from luteal stage ovaries were 12.5%, 17.5%, 12.5%, and 16.9%. Additionally, the differences between the study and control groups were significant in the case of follicular stage oocytes. Finally, supplementing the maturation medium with EGF and/or IGF-1 significantly enhanced the meiotic maturation of oocytes recovered from follicular stage ovaries. The present study also demonstrated that the combination of EGF and IGF-I provides an additional or synergic effect on meiotic maturation of oocytes recovered from the follicular stage. Copyright © 2014 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Comparative genomic hybridization (CGH) analysis of stage 4 neuroblastoma reveals high frequency of 11q deletion in tumors lacking MYCN amplification

NARCIS (Netherlands)

Plantaz, D.; Vandesompele, J.; van Roy, N.; Lastowska, M.; Bown, N.; Combaret, V.; Favrot, M. C.; Delattre, O.; Michon, J.; Bénard, J.; Hartmann, O.; Nicholson, J. C.; Ross, F. M.; Brinkschmidt, C.; Laureys, G.; Caron, H.; Matthay, K. K.; Feuerstein, B. G.; Speleman, F.

2001-01-01

We have studied the occurrence and association of 11q deletions with other chromosomal imbalances in Stage 4 neuroblastomas. To this purpose we have performed comparative genomic hybridization (CGH) analysis on 50 Stage 4 neuroblastomas and these data were analyzed together with those from 33

Recommendations for neoadjuvant pathologic staging (ypTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals.

Science.gov (United States)

Rice, Thomas W; Ishwaran, Hemant; Kelsen, David P; Hofstetter, Wayne L; Apperson-Hansen, Carolyn; Blackstone, Eugene H

2016-11-01

We report analytic and consensus processes that produced recommendations for neoadjuvant pathologic stage groups (ypTNM) of esophageal and esophagogastric junction cancer for the AJCC/UICC cancer staging manuals, 8th edition. The Worldwide Esophageal Cancer Collaboration provided data for 22,654 patients with epithelial esophageal cancers; 7,773 had pathologic assessment after neoadjuvant therapy. Risk-adjusted survival for each patient was developed. Random forest analysis identified data-driven neoadjuvant pathologic stage groups wherein survival decreased monotonically with increasing group, was distinctive between groups, and homogeneous within groups. An additional analysis produced data-driven anatomic neoadjuvant pathologic stage groups based only on ypT, ypN, and ypM categories. The AJCC Upper GI Task Force, by smoothing, simplifying, expanding, and assessing clinical applicability, produced consensus neoadjuvant pathologic stage groups. Grade and location were much less discriminating for stage grouping ypTNM than pTNM. Data-driven stage grouping without grade and location produced nearly identical groups for squamous cell carcinoma and adenocarcinoma. However, ypTNM groups and their associated survival differed from pTNM. The need for consensus process was minimal. The consensus groups, identical for both cell types were as follows: ypStage I comprised ypT0-2N0M0; ypStage II ypT3N0M0; ypStage IIIA ypT0-2N1M0; ypStage IIIB ypT3N1M0, ypT0-3N2, and ypT4aN0M0; ypStage IVA ypT4aN1-2, ypT4bN0-2, and ypTanyN3M0; and ypStage IVB ypTanyNanyM1. Absence of equivalent pathologic (pTNM) categories for the peculiar neoadjuvant pathologic categories ypTisN0-3M0 and ypT0N0-3M0, dissimilar stage group compositions, and markedly different early- and intermediate-stage survival necessitated a unified, unique set of stage grouping for patients of either cell type who receive neoadjuvant therapy. © 2016 International Society for Diseases of the Esophagus.

Hydroxamic acid content and toxicity of rye at selected growth stages.

Science.gov (United States)

Rice, Clifford P; Park, Yong Bong; Adam, Frédérick; Abdul-Baki, Aref A; Teasdale, John R

2005-08-01

Rye (Secale cereale L.) is an important cover crop that provides many benefits to cropping systems including weed and pest suppression resulting from allelopathic substances. Hydroxamic acids have been identified as allelopathic compounds in rye. This research was conducted to improve the methodology for quantifying hydroxamic acids and to determine the relationship between hydroxamic acid content and phytotoxicity of extracts of rye root and shoot tissue harvested at selected growth stages. Detection limits for an LC/MS-MS method for analysis of hydroxamic acids from crude aqueous extracts were better than have been reported previously. (2R)-2-beta-D-Glucopyranosyloxy-4-hydroxy-(2H)-1,4-benzoxazin-3(4H)-one (DIBOA-G), 2,4-dihydroxy-(2H)-1,4-benzoxazin-3(4H)-one (DIBOA), benzoxazolin-2(3H)-one (BOA), and the methoxy-substituted form of these compounds, (2R)-2-beta-D-glucopyranosyloxy-4-hydroxy-7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one (DIMBOA glucose), 2,4-hydroxy-7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one (DIMBOA), and 6-methoxy-benzoxazolin-2(3H)-one (MBOA), were all detected in rye tissue. DIBOA and BOA were prevalent in shoot tissue, whereas the methoxy-substituted compounds, DIMBOA glucose and MBOA, were prevalent in root tissue. Total hydroxamic acid concentration in rye tissue generally declined with age. Aqueous crude extracts of rye shoot tissue were more toxic than extracts of root tissue to lettuce (Lactuca sativa L.) and tomato (Lycopersicon esculentum Mill.) root length. Extracts of rye seedlings (Feekes growth stage 2) were most phytotoxic, but there was no pattern to the phytotoxicity of extracts of rye sampled at growth stages 4 to 10.5.4, and no correlation of hydroxamic acid content and phytotoxicity (I50 values). Analysis of dose-response model slope coefficients indicated a lack of parallelism among models for rye extracts from different growth stages, suggesting that phytotoxicity may be attributed to compounds with different modes of action at

Hodgkin disease of stage 4 from the national institute of oncology of Rabat-Morocco

International Nuclear Information System (INIS)

Mouhout, A.; Kebdani, T.; Hassouni, K.; Kanouni, L.; Assabane, A.; Kabbaj, H.; Rami, K.; Benjaafer, N.; Elgueddari, B.K.

2009-01-01

In spite of an improvement of the global survival rate in the order of 10 to 15% during the last thirty years, only 40% to 60% of patients with the hodgkin disease at 3B and 4 stages are living at ten years from the international data bases. (N.C.)

Accuracy of the One-Stage and Two-Stage Impression Techniques: A Comparative Analysis.

Science.gov (United States)

Jamshidy, Ladan; Mozaffari, Hamid Reza; Faraji, Payam; Sharifi, Roohollah

2016-01-01

Introduction . One of the main steps of impression is the selection and preparation of an appropriate tray. Hence, the present study aimed to analyze and compare the accuracy of one- and two-stage impression techniques. Materials and Methods . A resin laboratory-made model, as the first molar, was prepared by standard method for full crowns with processed preparation finish line of 1 mm depth and convergence angle of 3-4°. Impression was made 20 times with one-stage technique and 20 times with two-stage technique using an appropriate tray. To measure the marginal gap, the distance between the restoration margin and preparation finish line of plaster dies was vertically determined in mid mesial, distal, buccal, and lingual (MDBL) regions by a stereomicroscope using a standard method. Results . The results of independent test showed that the mean value of the marginal gap obtained by one-stage impression technique was higher than that of two-stage impression technique. Further, there was no significant difference between one- and two-stage impression techniques in mid buccal region, but a significant difference was reported between the two impression techniques in MDL regions and in general. Conclusion . The findings of the present study indicated higher accuracy for two-stage impression technique than for the one-stage impression technique.

Kraft pulp bleaching with molybdenum activated acid peroxide (PMo stage)

International Nuclear Information System (INIS)

Rabelo, Marcos Sousa

2009-01-01

Optimum conditions to run the P Mo stage for bleaching eucalyptus kraft pulp were 90 deg C, pH 3.5, 2 h, 0.1 kg/t Mo and 5 kg/t H 2 O 2 . The P Mo stage efficiency increased with decreasing pH (1.5-5.5) and increasing temperature (75-90 deg C), time (2-4 h), and hydrogen peroxide (3-10 kg/t) and molybdenum concentration (0.1-0.4 kg/t). The implementation of the P Mo stage, as replacement for the A stage, decreased total active chlorine demand of the OAZDP sequence by 6 kg/t to reach 90% ISO, both in laboratory and mill scale. Such practice resulted in decreased bleaching chemical costs to produce fully bleached pulp of 90% ISO. (author)

Synthesis and investigation of the physical-chemical properties of 2-(5-((theophylline-7'-ylmethyl-4-methyl-4H-1,2,4-triazole-3-ylthioacetic acid salts

Directory of Open Access Journals (Sweden)

A. S. Gotsulya

2016-12-01

Full Text Available At this stage of modern science development scientists get a lot of questions in the field of medicine and pharmacy. The study and search of new ways for synthesis of high-performance and low-toxic substances is one of the most important questions among them. Special attention is paid to 1,2,4-triazole and xanthine. On their basis some medical drugs have been previously made and are widely used in nowadays medicine. The aim of this work was the synthesis of salts of 2-(5-((theophylline-7'-ylmethyl-4-methyl-4H-1,2,4-triazole-3-ylthioacetic acid and the study of their properties. Methods and results. Theophylline has been selected as starting material. Through a number of stages 7'-((3-thio-4-methyl-4H-1,2,4-triazole-5-ylmethyltheophylline has been obtained. Salts with organic and inorganic bases have been obtained by the neutralization reaction in aqueous medium. The structure of the compounds has been confirmed with elemental analysis on Elemental Vario EL cube (Elementar Analysensysteme, Germany, IR spectra (4000–400 cm-1 have been taken off the module ALPHA-T of Bruker ALPHA FT-IR spectrometer (Bruker optics, Germany. Gear Liquid Chromatography System with Mass spectrometric detector (Agilent Technologies, USA: Agilent 1260 Infinity HPLC System; single quadrupole mass spectrometer Agilent 6120 with electrospray ionization (ESI; Open LAB CDS Software. The formation of salts has been confirmed by the signals corresponding to protonated amines. Conclusions. The optimal conditions of obtaining salts of 2-(5-((theophylline-7'-ylmethyl-4-methyl-4H-1,2,4-triazole-3-ylthioacetic acid with inorganic and organic bases have been determined. Corresponding carboxylic acid has been obtained by interaction of the resulting thiol with monochloroacetic acid in aqueous solution with double quantity of alkali and subsequent neutralization by hydrochloric acid. It has been confirmed that the greatest outputs of the reaction products were observed while using

Prognostic significance of Gleason score 7 (3+4 and Gleason score 7 (4+3 in prostatic adenocarcinoma in relation to clinical stage, androgen tissue status and degree of neuroendocrine differentiation

Directory of Open Access Journals (Sweden)

Mijović M.

2014-01-01

Full Text Available Prognosis and choice of treatment of adenocarcinoma of the prostate (ADCP directly depend on the numerous of predictive factors, among which the most important are summary histological tumor grade (Gleason score, which is the sum of the first and second dominant histological grade and clinical stage. According to recent research these factors include androgen tissue status and degree of neuroendocrine differentiation. The importance of the first and second dominant histological grade becomes particularly important in ADCP Gleason score 7. Tumors with worse prognosis considered to be ADCP of higher Gleason score, the advanced clinical stage, androgen independent tumors and tumors that show a higher degree of neuroendocrine differentiation. The aim of the study was to determine the predictive significance of ADCP Gleason score 7 (3+4 and ADCP Gleason score 7 (4+3 in relation to clinical stage, androgen tissue status and degree of focal neuroendocrine differentiation. The study included 33 ADCP of Gleason score 7,26 (78.79% ADCP 7 (3+4 and 7 (21.21% ADCP 7 (4+3. All tumors are most often diagnosed with stage D2, when there are already distant metastases. ADCP of Gleason score 7 (4+3 were diagnosed more often at this stage, among them there are more androgen independent tumors and they show a greater degree of focal neuroendocrine differentiation. All the results are in accordance with data from the literature suggesting that ADCP of Gleason score 7 (4+3 have a worse prognosis than ADCP of Gleason score 7 (3 +4.

(3,5-Dimethylpyrazol-1-yl-[4-(1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-ylaminophenyl]methanone

Directory of Open Access Journals (Sweden)

Rania B. Bakr

2016-11-01

Full Text Available In an attempt to enhance cytotoxic activity of pyrazolo[3,4-d]pyrimidine core, we synthesized (3,5-dimethylpyrazol-1-yl-[4-(1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-ylaminophenyl]methanone (4 by reacting 4-(1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-ylaminobenzohydrazide (3 with acetylacetone. Antiproliferative activity of this compound was screened against breast (MCF-7, colon (HCT-116, and liver (HEPG-2 cancer cell lines. The tested compound exhibited cytotoxic activity with IC50 = 5.00–32.52 μM. Moreover, inhibitory activity of this compound was evaluated against the epidermal growth factor receptor (EGFR, the fibroblast growth factor receptor (FGFR, the insulin receptor (IR, and the vascular endothelial growth factor receptor (VEGFR. This target compound showed potent inhibitory activity, especially against FGFR with IC50 = 5.18 μM.

Eag1 channels as potential early-stage biomarkers of hepatocellular carcinoma

Directory of Open Access Journals (Sweden)

Chávez-López MG

2016-09-01

Full Text Available María de Guadalupe Chávez-López,1 Violeta Zúñiga-García,1 Julio Isael Pérez-Carreón,2 Arturo Avalos-Fuentes,3 Yesenia Escobar,4 Javier Camacho1 1Department of Pharmacology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, 2Instituto Nacional de Medicina Genómica, 3Department of Physiology, Biophysics and Neuroscience, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, 4Centro de Investigación Clínica Acelerada Sc, Mexico City, Mexico Abstract: Hepatocellular carcinoma (HCC is a major cause of cancer death worldwide. HCC is usually asymptomatic at potential curative stages, and it has very poor prognosis if detected later. Thus, the identification of early biomarkers and novel therapies is essential to improve HCC patient survival. Ion channels have been proposed as potential tumor markers and therapeutic targets for several cancers including HCC. Especially, the ether à-go-go-1 (Eag1 voltage-gated potassium channel has been suggested as an early marker for HCC. Eag1 is overexpressed during HCC development from the cirrhotic and the preneoplastic lesions preceding HCC in a rat model. The channel is also overexpressed in human HCC. Astemizole has gained great interest as a potential anticancer drug because it targets several proteins involved in cancer including Eag1. Actually, in vivo studies have shown that astemizole may have clinical utility for HCC prevention and treatment. Here, we will review first some general aspects of HCC including the current biomarkers and therapies, and then we will focus on Eag1 channels as promising tools in the early diagnosis of HCC. Keywords: ion channels, Eag1, hepatocellular carcinoma, astemizole, diethylnitrosamine

Safety, pharmacokinetics, immunogenicity, and biodistribution of (186)Re-labeled humanized monoclonal antibody BIWA 4 (Bivatuzumab) in patients with early-stage breast cancer.

Science.gov (United States)

Koppe, Manuel; Schaijk, Frank van; Roos, Jan; Leeuwen, Paul van; Heider, Karl-Heinz; Kuthan, Hartmut; Bleichrodt, Robert

2004-12-01

The aim of this prospective study was to evaluate the safety, pharmacokinetics, immunogenicity, and biodistribution of (186)Re-labeled humanized anti-CD44v6 monoclonal antibody (MAb( BIWA 4 (Bivatuzumab( in 9 patients with early-stage breast cancer. Radioimmunoscintigraphy (RIS( was performed within 1, 24, and 72 hours after administration. BIWA 4 concentration in plasma (ELISA and radioactivity measurements( and the development of human antihuman antibody (HAHA( responses was determined. The biodistribution of (186)Re-BIWA 4 was determined by radioactivity measurements in tumor and normal tissue biopsies obtained during surgery 1 week after administration. Administration of (186)Re-BIWA 4 was well tolerated by all patients and no HAHA responses were observed. The mean t(1/2) in plasma of BIWA 4 (ELISA( was 81 hours (range, 67-97(, whereas the mean radioactivity t(1/2) tended to be longer, at 105 hours (range, 90-114(. RIS unmistakably showed the tumor in 3 patients. Less clear identifications were established in 3 additional patients. In 2 patients, the tumor was wrongly identified in the contralateral breast. Median tumor CD44v6 expression, as determined by immunohistochemistry, was 70% (range, 10-90%). Mean tumor uptake was 2.96% ID/kg (range, 0.92-6.27(, with no apparent correlation with either tumor CD44v6 expression, tumor-cell cellularity, or tumor diameter. Tumor-to-nontumor ratios were unfavorable for blood, bone marrow, mammary gland tissue, and skin. The (186)Re-labeled humanized MAb BIWA 4 can safely be administered to patients with early-stage breast cancer. Tumorto- nontumor ratios were unfavorable, with no apparent correlation with CD44v6 expression, tumor-cell cellularity, or tumor diameter. BIWA 4, therefore, appears to have limitations as a vehicle for radioimmunotherapy in patients with breast cancer.

Monocarboxylate transporters 1-4 in NSCLC: MCT1 is an independent prognostic marker for survival.

Directory of Open Access Journals (Sweden)

Marte Eilertsen

Full Text Available INTRODUCTION: Monocarboxylate transporters (MCTs 1-4 are lactate transporters crucial for cancers cells adaption to upregulated glycolysis. Herein, we aimed to explore their prognostic impact on disease-specific survival (DSS in both cancer and tumor stromal cells in NSCLC. METHODS: Tissue micro arrays (TMAs were constructed, representing both cancer and stromal tumor tissue from 335 unselected patients diagnosed with stage I-IIIA NSCLC. Immunohistochemistry was used to evaluate the expression of MCT1-4. RESULTS: In univariate analyses; ↓ MCT1 (P = 0.021 and ↑ MCT4 (P = 0.027 expression in cancer cells, and ↑ MCT1 (P = 0.003, ↓ MCT2 (P = 0.006, ↓ MCT3 (P = 0.020 expression in stromal cells correlated significantly with a poor DSS. In multivariate analyses; ↓ MCT1 expression in cancer cells (HR: 1.9, CI 95%: 1.3-2.8, P = 0.001, ↓ MCT2 (HR: 2.4, CI 95%: 1.5-3.9, P<0.001, ↓ MCT3 (HR: 1.9, CI 95%: 1.1-3.5, P = 0.031 and ↑ MCT1 expression in stromal cells (HR: 1.7, CI 95%: 1.1-2.7, P = 0.016 were significant independent poor prognostic markers for DSS. CONCLUSIONS: We provide novel information of MCT1 as a candidate marker for prognostic stratification in NSCLC. Interestingly, MCT1 shows diverging, independent prognostic impact in the cancer cell and stromal cell compartments.

Adjuvant radiotherapy for pathologic stage T3/4 adenocarcinoma of the prostate: Ten-year update

International Nuclear Information System (INIS)

Anscher, Mitchell S.; Robertson, Cary N.; Prosnitz, Leonard R.

1995-01-01

Purpose: To determine the role of adjuvant postoperative radiotherapy (RT) following radical prostatectomy (RP) in a group of patients with pathologic Stage T3/4 adenocarcinoma of the prostate followed for a median of 10 years after treatment. Methods and Materials: Between 1970 and 1983, 159 patients underwent RP for newly diagnosed adenocarcinoma of the prostate and were found to have pathologic Stage T3/4 tumors. Forty-six received adjuvant RT and 113 did not. Radiotherapy usually consisted of 45-50 Gy to the whole pelvis followed by a boost to the prostate bed of 10-15 Gy, to a total dose of 55-65 Gy. Patients were analyzed with respect to survival, disease-free survival, local control, and freedom from distant metastases. A rising prostate-specific antigen in the absence of other evidence of relapse was scored as a separate category of recurrence. Results: Both groups of patients have been followed for a median of 10 years. The actuarial survival at 10 and 15 years was 62% and 62% for the RT group compared to 52% and 37%, respectively, for the RP group (p = 0.18). The disease-free survival for the RT group was 55% and 48% at 10 and 15 years, respectively, compared to 37% and 33% for the RP group (p = 0.16). Similarly, there was no difference in the rate of distant metastases between the two groups. In contrast, the local relapse rate was significantly reduced by the addition of postoperative radiotherapy. The actuarial local control rate at 10 and 15 years was 92% and 82%, respectively, for the RT group vs. 60% and 53% for the RP group (p 0.002). Conclusions: While postoperative pelvic RT significantly improves local control compared to RP alone for pathologic Stage T3/4 prostate cancer, it has no impact on distant metastases and consequently does not improve survival. These data are consistent with the conclusion that many patients with pathologic Stage T3/4 prostate cancer have occult metastases at presentation and will not be cured by local therapies alone

Identification of transplanting stage of rice using Sentinel-1 data

Science.gov (United States)

Hongo, C.; Tosa, T.; Tamura, E.; Sigit, G.; Barus, B.

2017-12-01

As the adaptation of climate change, the Government of Indonesia has launched agricultural insurance program for damage of rice by drought, flood and pest and disease. For assessment of the damage ratio and calculation of indemnity, extraction of paddy field and identification of transplanting stage are key issues. In this research, we conducted identification of rice transplanting stage in dry season of 2015, using data from Sentinel-1, for paddy in Cianjur, West Java, Indonesia. As the first step, time series order of backscattering coefficient was analyzed about paddy, forest, villages and fish farming ponds with use of Sentinel-1 data acquired on April 1, April 13, April 25, May 7, May 19, June 24, July 18 and August 11. The result shows that the backscattering coefficient of paddy substantially decreased from data on May 7 and reached minimum value and then after increased toward June. A paddy area showing this change was almost the same area where rice was at harvesting stage and we did field investigation work from August 11 to 13. Considering a growth period of rice in our research site was about 110 days, so the result supported the fact that transplantation of rice was done around May 7. On the other hand, backscattering coefficient of forest, villages and fish farming ponds was constant and showed clear difference from the coefficient of paddy. As the next step, minimum and maximum value of backscattering coefficient were extracted from the data of May 7, May 19 and June 24, respectively. Then increase amount was calculated by deducting the minimum value from the maximum. Finally, using the minimum value of backscattering coefficient and the increased amount, a classification of image was made to identify transplanting stage through maximum likelihood method, decision tree method and threshold setting method (regression analysis by 3σ-rule). As the result, the maximum likelihood method made the most accurate distinguishment about transplanting stage

Preoperative staging and treatment options in T1 rectal adenocarcinoma

DEFF Research Database (Denmark)

Baatrup, Gunnar; Endreseth, Birger H; Isaksen, Vidar

2009-01-01

. Results. Local treatment of T1 cancers combined with close follow-up, early salvage surgery or later radical resection of local recurrences or with chemo-radiation may lead to fewer severe complications and comparable, or even better, long-term survival. Accurate preoperative staging and careful selection...... of patients for local or non-operative treatment are mandatory. As preoperative staging, at present, is not sufficiently accurate, strategies for completion, salvage or rescue surgery is important, and must be accepted by the patient before local treatment for cure is initiated. Recommendations......Background. Major rectal resection for T1 rectal cancer offers more than 95% cancer specific five-year survival to patients surviving the first 30 days after surgery. A significant further improvement by development of the surgical technique may not be possible. Improvements in the total survival...

Saturn V First Stage (S-1C) Ready for Assembly AT KSC

Science.gov (United States)

1968-01-01

This photograph shows the Saturn V first stage (S-1C) in the Vehicle Assembly Building at Kennedy Space Center ready to be mated with the second and third stages to complete the assembly of a Saturn V launch vehicle. This particular Saturn V was used for Apollo 6, which was a systems test flight. The towering 363-foot Saturn V was a multi-stage, multi-engine launch vehicle standing taller than the Statue of Liberty. Altogether, the Saturn V engines produced as much power as 85 Hoover Dams.

Spectral Analysis of 3-(Adamantan-1-yl)-4-Ethyl-1-[(4-Phenylpiperazin-1-yl) Methyl]-1 H-1,2,4-Triazole-5(4 H)-Thione

Science.gov (United States)

Mindarava, Y. L.; Shundalau, M. B.; Al-Wahaibi, L. H.; El-Emam, A. A.; Matsukovich, A. S.; Gaponenko, S. V.

2018-05-01

Vibrational IR (3200-650 cm-1) and Raman spectra (3200-150 cm-1) of adamantane-containing 3-(adamantan-1-yl)-4-ethyl-1-[(4-phenylpiperazin-1-yl)methyl]-1H-1,2,4-triazole-5(4H)-thione, which is promising for drug design, were examined. The UV/Vis spectrum (450-200 nm) of the compound in EtOH was measured. Full geometry optimization using density functional theory (DFT) in the B3LYP/cc-pVDZ approximation allowed the equilibrium configuration of the molecule to be determined and IR and Raman spectra to be calculated. Based on these, the experimental vibrational IR and Raman spectra were interpreted and the biological activity indices were predicted. The UV/Vis spectrum of the title compound was simulated at the time-dependent DFT/CAM-B3LYP/cc-pVDZ level with and without solvent effects and at the ab initio multi-reference perturbation theory XMCQDPT2 level. The UV/Vis spectrum that was simulated using the multi-reference XMCQDPT2 approximation agreed very successfully with the experimental data, in contrast to the single-reference DFT method. This was probably a consequence of intramolecular charge transfer.

Spectral Analysis of 3-(Adamantan-1-yl)-4-Ethyl-1-[(4-Phenylpiperazin-1-yl) Methyl]-1H-1,2,4-Triazole-5(4H)-Thione

Science.gov (United States)

Mindarava, Y. L.; Shundalau, M. B.; Al-Wahaibi, L. H.; El-Emam, A. A.; Matsukovich, A. S.; Gaponenko, S. V.

2018-05-01

Vibrational IR (3200-650 cm-1) and Raman spectra (3200-150 cm-1) of adamantane-containing 3-(adamantan-1-yl)-4-ethyl-1-[(4-phenylpiperazin-1-yl)methyl]-1H-1,2,4-triazole-5(4H)-thione, which is promising for drug design, were examined. The UV/Vis spectrum (450-200 nm) of the compound in EtOH was measured. Full geometry optimization using density functional theory (DFT) in the B3LYP/cc-pVDZ approximation allowed the equilibrium configuration of the molecule to be determined and IR and Raman spectra to be calculated. Based on these, the experimental vibrational IR and Raman spectra were interpreted and the biological activity indices were predicted. The UV/Vis spectrum of the title compound was simulated at the time-dependent DFT/CAM-B3LYP/cc-pVDZ level with and without solvent effects and at the ab initio multi-reference perturbation theory XMCQDPT2 level. The UV/Vis spectrum that was simulated using the multi-reference XMCQDPT2 approximation agreed very successfully with the experimental data, in contrast to the single-reference DFT method. This was probably a consequence of intramolecular charge transfer.

Visual assessment of the cervical vertebral maturation stages: A study of diagnostic accuracy and repeatability.

Science.gov (United States)

Perinetti, Giuseppe; Caprioglio, Alberto; Contardo, Luca

2014-11-01

To evaluate the diagnostic accuracy and repeatability of the visual assessment of the cervical vertebral maturation (CVM) stages. Ten operators underwent training sessions in visual assessment of CVM staging. Subsequently, they were asked to stage 72 cases equally divided into the six stages. Such assessment was repeated twice in two sessions (T1 and T2) 4 weeks apart. A reference standard for each case was created according to a cephalometric analysis of both the concavities and shapes of the cervical vertebrae. The overall agreement with the reference standard was about 68% for both sessions and 76.9% for intrarater repeatability. The overall kappa coefficients with the reference standard were up to 0.86 for both sessions, and 0.88 for intrarater repeatability. Overall, disagreements one stage and twp stage apart were 23.5% (T1) and 5.1% (T2), respectively. Sensitivity ranged from 53.3% for CS5 (T1) to 99.9% for CS1 (T2), positive predictive values ranged from 52.4% for CS5 (T2) to 94.3% for CS6 (T1), and accuracy ranged from 83.6% for CS4 (T2) to 94.9% for CS1 (T1). Visual assessment of the CVM stages is accurate and repeatable to a satisfactory level. About one in three cases remain misclassified; disagreement is generally limited to one stage and is mostly seen in stages 4 and 5.

[Using (1)H-nuclear magnetic resonance metabolomics and gene ontology to establish pathological staging model for esophageal cancer patients].

Science.gov (United States)

Chen, X; Wang, K; Chen, W; Jiang, H; Deng, P C; Li, Z J; Peng, J; Zhou, Z Y; Yang, H; Huang, G X; Zeng, J

2016-07-01

By combining the metabolomics and computational biology, to explore the relationship between metabolic phenotype and pathological stage in esophageal cancer patients, to find the mechanism of metabolic network disturbance and develop a new method for fast preoperative clinical staging. A prospective cohort study (from April 2013 to January 2016) was conducted. The preoperative patients from Sichuan Provincial People's Hospital, who were diagnosed with esophageal cancer from May 2013 to April 2014 were included, and their serum samples were collected to detect (1)H-nuclear magnetic resonance (NMR) metabolomics for the purpose of drawing the metabolic fingerprinting in different stages of patients with esophageal cancer. The data were processed with these methods-principal components analysis: partial least squares regression and support vector machine, for the exploration of the enzyme-gene network regulatory mechanism in abnormal esophageal cancer metabolic network regulation and to build the quantitative prediction model of esophageal cancer staging in the end. All data were processed on high-performance computing platforms Matalab. The comparison of data had used Wilcoxon test, variance analysis, χ(2) test and Fisher exact test. Twenty patients with different stages of esophageal cancer were included; and their serum metabolic fingerprinting could differentiate different tumor stages. There were no difference among the five teams in the age (F=1.086, P>0.05), the body mass index (F=1.035, P>0.05), the distance from the incisors to tumor (F=1.078, P>0.05). Among the patients with different TNM stages, there was a significant difference in plasma metabolome. Compared to ⅡB, ⅢA, Ⅳstage patients, increased levels of butanone, ethanol amine, homocysteine, hydroxy acids and estriol, together with decreased levels of glycoprotein, creatine, choline, isobutyricacid, alanine, leucine, valine, were observed inⅠB, ⅡA stage patients. Four metabolic markers

Confinement and clearance of OCT4 in the porcine embryo at stereomicroscopically defined stages around gastrulation

DEFF Research Database (Denmark)

Vejlsted, Morten; Offenberg, Hanne Kjær; Thorup, Flemming

2006-01-01

was selectively observed in the epiblast. A prominent crescent-shaped thickening at the posterior region of the embryonic disk marked the first polarization within this structure reflecting incipient cell ingression. Following differentiation of the epiblast, clearance of OCT4 from the three germ layers......In the areas of developmental biology and embryonic stem cell research, reliable molecular markers of pluripotency and early lineage commitment are sparse in large animal species. In this study, we present morphological and immunohistochemical findings on the porcine embryo in the period around...... gastrulation, days 8-17 postinsemination, introducing a steromicroscopical staging system in this species. In embryos at the expanding hatched blastocyst stage, OCT4 is confined to the inner cell mass. Following detachment of the hypoblast, and formation of the embryonic disk, this marker of pluripotency...

Action of ethylene, 1-methylcyclopropene and silver thiosulfate in two developmental stages of potted ornamental pepper(

Directory of Open Access Journals (Sweden)

Paula Cristina Carvalho Lima

2017-09-01

Full Text Available The species of Capsicum genus have great genetic variability with enormous potential for marketing as ornamental potted plants. The exposure at ethylene induces various deleterious responses during plants life cycle, but there are few studies on how the ethylene affects early developmental stages of these ornamental plants. Thus, this study aimed to evaluate the effects of the application of ethylene and ethylene inhibitors, 1-methylcyclopropene (1-MCP and silver thiosulphate (STS in two early development stages (seedling or initial flowering of potted ornamental peppers of the cultivars ‘Calypso’ and ‘MG 302’. Cultivar ‘MG 302’ showed intermediate sensitivity to ethylene, while the cultivar ‘Calypso’ showed complete abscission of leaves when exposed to 10 µl of ethylene for 48 hours in both development stages. Plants treated with 1-MCP showed similar durability to control for both varieties and developmental stages, and the treatment with 1-MCP + ethylene was beneficial only for ‘MG 302’. STS was the most efficient substance in delaying the ethylene, wherein at stage 1 there was no leaf abscission and at stage 2 had much reduced leaf abscission occurred, regardless the cultivar. Treatment with STS + ethylene was efficient only at stage 1 for ‘Calypso’ and at stage 2 for ‘MG 302’. According to the data, cultivars showed different levels of sensitivity to ethylene, ‘Calypso’ is very sensitive and ‘MG 302’ showed intermediate sensitivity. Regardless the cultivar, STS treatment significantly blocked the ethylene action in both development stages and the use of 1-MCP was less efficient

1,1′-{1,4-Phenylene bis[3-(6-chloro-2-methyl-4-phenylquinolin-3-yl-4,5-dihydro-1H-pyrazole-5,1-diyl]}dibutan-1-one

Directory of Open Access Journals (Sweden)

Allaoua Kedjadja

2015-10-01

Full Text Available A new polycyclic compound, 1,1′-{1,4-phenylene bis[3-(6-chloro-2-methyl-4-phenylquinolin-3-yl-4,5-dihydro-1H-pyrazole-5,1-diyl]}dibutan-1-one (3 has been synthesized by cyclocondensation of (2E,2′E-1,1′-bis(6-chloro-2-methyl-4-phenylquinolin-3-yl-3,3′-(1,4-phenylenediprop-2-en-1-one (2 and hydrazine hydrate in butanoic acid. The structure of this compound was established by elemental analysis, 1H-NMR, 13C-NMR, mass and IR spectroscopy.

Neuronal glucose metabolism is impaired while astrocytic TCA cycling is unaffected at symptomatic stages in the hSOD1G93A mouse model of amyotrophic lateral sclerosis.

Science.gov (United States)

Tefera, Tesfaye W; Borges, Karin

2018-01-01

Although alterations in energy metabolism are known in ALS, the specific mechanisms leading to energy deficit are not understood. We measured metabolite levels derived from injected [1- 13 C]glucose and [1,2- 13 C]acetate (i.p.) in cerebral cortex and spinal cord extracts of wild type and hSOD1 G93A mice at onset and mid disease stages using high-pressure liquid chromatography, 1 H and 13 C nuclear magnetic resonance spectroscopy. Levels of spinal and cortical CNS total lactate, [3- 13 C]lactate, total alanine and [3- 13 C]alanine, but not cortical glucose and [1- 13 C]glucose, were reduced mostly at mid stage indicating impaired glycolysis. The [1- 13 C]glucose-derived [4- 13 C]glutamate, [4- 13 C]glutamine and [2- 13 C]GABA amounts were diminished at mid stage in cortex and both time points in spinal cord, suggesting decreased [3- 13 C]pyruvate entry into the TCA cycle. Lack of changes in [1,2- 13 C]acetate-derived [4,5- 13 C]glutamate, [4,5- 13 C]glutamine and [1,2- 13 C]GABA levels indicate unchanged astrocytic 13 C-acetate metabolism. Reduced levels of leucine, isoleucine and valine in CNS suggest compensatory breakdown to refill TCA cycle intermediate levels. Unlabelled, [2- 13 C] and [4- 13 C]GABA concentrations were decreased in spinal cord indicating that impaired glucose metabolism contributes to hyperexcitability and supporting the use of treatments which increase GABA amounts. In conclusion, CNS glucose metabolism is compromised, while astrocytic TCA cycling appears to be normal in the hSOD1 G93A mouse model at symptomatic disease stages.

Crystal structure of the human 4-1BB/4-1BBL complex.

Science.gov (United States)

Gilbreth, Ryan N; Oganesyan, Vaheh Y; Amdouni, Hamza; Novarra, Shabazz; Grinberg, Luba; Barnes, Arnita; Baca, Manuel

2018-05-02

4-1BBL is a member of the TNF superfamily and is the ligand for the TNFRsuperfamily receptor, 4-1BB. 4-1BB plays an immunomodulatory role in T cells and NK cells and agonists of this receptor have garnered strong attention as potentialimmunotherapy agents. Broadly speaking, the structural features of TNF superfamilymembers, their receptors and ligand/receptor complexes are similar. However, apublished crystal structure of human 4-1BBL suggests that it may be unique in thisregard, exhibiting a three-bladed propeller-like trimer assembly that is distinctly different from that observed in other family members. This unusual structure also suggests that the human 4-1BB/4-1BBL complex may be structurally unique within the TNF/TNFR superfamily, but to date no structural data have been reported. Here we report the crystal structure of the human 4-1BB/4-1BBL complex at 2.4 Å resolution. In this structure, 4-1BBL does not adopt the unusual trimer assembly previously reported, but instead forms a canonical bell-shaped trimer typical of other TNF superfamily members. The structure of 4-1BB is also largely canonical as is the 4-1BB/4-1BBL complex. Mutational data support the 4-1BBL structure reported here as being biologically relevant, suggesting that the previously reported structure is not. Together, the data presented here offer insight into structure/function relationships in the 4-1BB/4-1BBL system and improve our structural understanding of the TNF/TNFR superfamily more broadly. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

IPP-rich milk protein hydrolysate lowers blood pressure in subjects with stage 1 hypertension, a randomized controlled trial

Directory of Open Access Journals (Sweden)

Kloek Joris

2010-11-01

Full Text Available Abstract Background Milk derived peptides have been identified as potential antihypertensive agents. The primary objective was to investigate the effectiveness of IPP-rich milk protein hydrolysates (MPH on reducing blood pressure (BP as well as to investigate safety parameters and tolerability. The secondary objective was to confirm or falsify ACE inhibition as the mechanism underlying BP reductions by measuring plasma renin activity and angiotensin I and II. Methods We conducted a randomized, placebo-controlled, double blind, crossover study including 70 Caucasian subjects with prehypertension or stage 1 hypertension. Study treatments consisted of daily consumption of two capsules MPH1 (each containing 7.5 mg Isoleucine-Proline-Proline; IPP, MPH2 (each containing 6.6 mg Methionine-Alanine-Proline, 2.3 mg Leucine-Proline-Proline, 1.8 mg IPP, or placebo (containing cellulose for 4 weeks. Results In subjects with stage 1 hypertension, MPH1 lowered systolic BP by 3.8 mm Hg (P = 0.0080 and diastolic BP by 2.3 mm Hg (P = 0.0065 compared with placebo. In prehypertensive subjects, the differences in BP between MPH1 and placebo were not significant. MPH2 did not change BP significantly compared with placebo in stage I hypertensive or prehypertensive subjects. Intake of MPHs was well tolerated and safe. No treatment differences in hematology, clinical laboratory parameters or adverse effects were observed. No significant differences between MPHs and placebo were found in plasma renin activity, or angiotensin I and II. Conclusions MPH1, containing IPP and no minerals, exerts clinically relevant BP lowering effects in subjects with stage 1 hypertension. It may be included in lifestyle changes aiming to prevent or reduce high BP. Trial registration ClinicalTrials.gov NCT00471263

Accuracy of the One-Stage and Two-Stage Impression Techniques: A Comparative Analysis

Directory of Open Access Journals (Sweden)

Ladan Jamshidy

2016-01-01

Full Text Available Introduction. One of the main steps of impression is the selection and preparation of an appropriate tray. Hence, the present study aimed to analyze and compare the accuracy of one- and two-stage impression techniques. Materials and Methods. A resin laboratory-made model, as the first molar, was prepared by standard method for full crowns with processed preparation finish line of 1 mm depth and convergence angle of 3-4°. Impression was made 20 times with one-stage technique and 20 times with two-stage technique using an appropriate tray. To measure the marginal gap, the distance between the restoration margin and preparation finish line of plaster dies was vertically determined in mid mesial, distal, buccal, and lingual (MDBL regions by a stereomicroscope using a standard method. Results. The results of independent test showed that the mean value of the marginal gap obtained by one-stage impression technique was higher than that of two-stage impression technique. Further, there was no significant difference between one- and two-stage impression techniques in mid buccal region, but a significant difference was reported between the two impression techniques in MDL regions and in general. Conclusion. The findings of the present study indicated higher accuracy for two-stage impression technique than for the one-stage impression technique.

SSX2-4 expression in early-stage non-small cell lung cancer

DEFF Research Database (Denmark)

Greve, K B V; Pøhl, M; Olsen, K E

2014-01-01

The expression of cancer/testis antigens SSX2, SSX3, and SSX4 in non-small cell lung cancers (NSCLC) was examined, since they are considered promising targets for cancer immunotherapy due to their immunogenicity and testis-restricted normal tissue expression. We characterized three SSX antibodies...... was only detected in 5 of 143 early-stage NSCLCs, which is rare compared to other cancer/testis antigens (e.g. MAGE-A and GAGE). However, further studies are needed to determine whether SSX can be used as a prognostic or predictive biomarker in NSCLC....

Modulation of Kir4.1 and Kir4.1-Kir5.1 channels by extracellular cations

DEFF Research Database (Denmark)

Søe, Rikke; Andreasen, Mogens; Klærke, Dan Arne

2009-01-01

This work demonstrates that extracellular Na(+) modulates the cloned inwardly rectifying K(+) channels Kir4.1 and Kir4.1-Kir5.1. Whole-cell patch clamp studies on astrocytes have previously indicated that inward potassium currents are regulated by external Na(+). We expressed Kir4.1 and Kir4.1-Kir5.......1 in Xenopus oocytes to disclose if Kir4.1 and/or Kir4.1-Kir5.1 at the molecular level are responsible for the observed effect of [Na(+)](o) and to investigate the regulatory mechanism of external cations further. Our results showed that Na(+) has a biphasic modulatory effect on both Kir4.1 and Kir4.1-Kir5.......1 currents. Depending on the Na(+)-concentration and applied voltage, the inward Kir4.1/Kir4.1-Kir5.1 currents are either enhanced or reduced by extracellular Na(+). The Na(+) activation was voltage-independent, whereas the Na(+)-induced reduction of the Kir4.1 and Kir4.1-Kir5.1 currents was both...

Staged residential post-acute rehabilitation for adults following acquired brain injury: A comparison of functional gains rated on the UK Functional Assessment Measure (UK FIM+FAM) and the Mayo-Portland Adaptability Inventory (MPAI-4).

Science.gov (United States)

Jackson, Diana; Seaman, Karla; Sharp, Kristylee; Singer, Rachel; Wagland, Janet; Turner-Stokes, Lynne

2017-01-01

To compare the UK Functional Assessment Measure (UK FIM+FAM) and Mayo-Portland Adaptability Inventory (MPAI-4) as measures of functional change in patients with brain injury receiving a staged residential post-acute community-based rehabilitation programme. Longitudinal cohort study of consecutive admissions (N = 42) over 3 years. Patients were assessed at admission and discharge/annual review. We examined groups according to stage of independence on admission: Maximum support (stages 1 and 2: N = 17); moderate/maximum self-care/household support (stage 3: N = 15); minimal self-care and moderate household/community support (stages 4-6: N = 10). Median (IQR) age: 50 (37-56) years. Male:female ratio: (71%:29%). Aetiology: stroke (50%), traumatic (36%) and other brain injuries (14%). Both tools demonstrated significant gains in overall scores and all subscales (p MPAI-4 was more sensitive to changes in adjustment and participation for clients admitted in the later stages (4-6). The UK FIM+FAM and MPAI-4 provide complementary evaluation across functional tasks ranging from self-care to participation. This study supports their use for longitudinal outcome evaluation in community residential rehabilitation services that take patients at different stages of recovery.

Staging of intestinal- and diffuse-type gastric cancers with the OLGA and OLGIM staging systems.

Science.gov (United States)

Cho, S-J; Choi, I J; Kook, M-C; Nam, B-H; Kim, C G; Lee, J Y; Ryu, K W; Kim, Y-W

2013-11-01

Operative link on gastritis assessment (OLGA) and Operative link on gastric intestinal metaplasia assessment (OLGIM) staging systems have been proposed for gastric cancer (GC) risk estimation. To validate the OLGA and OLGIM staging systems in a region with high risk of GC. This retrospective study included 474 GC patients and age- and sex-matched health screening control persons in a cancer centre hospital. We classified gastritis patterns according to the OLGA and OLGIM systems using the histological database that a pathologist prospectively evaluated using the updated Sydney system. GC risk according to the OLGA and OLGIM stages was evaluated using logistic regression analysis. More GC patients had OLGA stages III-IV (46.2%) than controls (26.6%, P diffuse-type GCs (30.9%). OLGA stages III and IV were significantly associated with increased risk of GC [odds ratios (ORs), 2.09; P = 0.008 and 2.04; P = 0.014 respectively] in multivariate analysis. The association was more significant for intestinal-type (ORs, 4.76; P = 0.001 and 4.19; P = 0.002 respectively), but not diffuse-type GC. OLGIM stages from I to IV were significantly associated with increased risk of both intestinal-type (ORs, 3.64, 5.15, 7.89 and 13.20 respectively) and diffuse-type GC (ORs, 1.84, 2.59, 5.08 and 6.32 respectively) with a significantly increasing trend. As high OLGA and OLGIM stages are independent risk factors for gastric cancer, the staging systems may be useful for risk assessment in high-risk regions, especially for intestinal-type gastric cancer. © 2013 John Wiley & Sons Ltd.

Risk factors for late-stage HIV disease presentation at initial HIV diagnosis in Durban, South Africa.

Directory of Open Access Journals (Sweden)

Paul K Drain

Full Text Available After observing persistently low CD4 counts at initial HIV diagnosis in South Africa, we sought to determine risk factors for late-stage HIV disease presentation among adults.We surveyed adults prior to HIV testing at four outpatient clinics in Durban from August 2010 to November 2011. All HIV-infected adults were offered CD4 testing, and late-stage HIV disease was defined as a CD4 count <100 cells/mm(3. We used multivariate regression models to determine the effects of sex, emotional health, social support, distance from clinic, employment, perceived barriers to receiving healthcare, and foregoing healthcare to use money for food, clothing, or housing ("competing needs to healthcare" on presentation with late-stage HIV disease.Among 3,669 adults screened, 830 were enrolled, newly-diagnosed with HIV and obtained a CD4 result. Among those, 279 (33.6% presented with late-stage HIV disease. In multivariate analyses, participants who lived ≥5 kilometers from the test site [adjusted odds ratio (AOR 2.8, 95% CI 1.7-4.7], reported competing needs to healthcare (AOR 1.7, 95% CI 1.2-2.4, were male (AOR 1.7, 95% CI 1.2-2.3, worked outside the home (AOR 1.5, 95% CI 1.1-2.1, perceived health service delivery barriers (AOR 1.5, 95% CI 1.1-2.1, and/or had poor emotional health (AOR 1.4, 95% CI 1.0-1.9 had higher odds of late-stage HIV disease presentation.Independent risk factors for late-stage HIV disease presentation were from diverse domains, including geographic, economic, demographic, social, and psychosocial. These findings can inform various interventions, such as mobile testing or financial assistance, to reduce the risk of presentation with late-stage HIV disease.

Computed tomography in staging of bladder carcinoma (Prospective study)

International Nuclear Information System (INIS)

Lee, Kyung Soo; Choi, Byung Ihn; Han, Man Chung

1985-01-01

Staging of carcinoma of the urinary bladder is important for the choice of therapy and also has prognostic implications. Hitherto the staging has been based upon cystoscopy with biopsy, transurethral resection, and palpation with complementary radiographic examinations such as cystography, urography, lymphangiography, ultrasound and angiography. However, with all these methods, the staging of bladder carcinomas still uncertain and inferior to CT. Authors analyzed CT staging of bladder cancers and compared with pathologic staging of laparotomy results. The results are as following: 1. Overall accuracy of CT staging in bladder carcinoma was 72 percent. 2. Overstaging was 20 percent (5/25) and understaging was 8 percent (2/25). 3. All of CT stage B cancers were proven to be stage B, pathologically. 4. In 6 cases of CT static cancers, only one was correct, 3 were overstaged and 2 were understaged. 5. In 7 cases of CT stage D cancers, 5 were correct and 2 were overstaged. 6. CT detected only 2 cases of pelvic lymph node involvement in 4 of pathologically proven lymphadenopathy

Adverse obstetric outcomes in women with previous cesarean for dystocia in second stage of labor.

Science.gov (United States)

Jastrow, Nicole; Demers, Suzanne; Gauthier, Robert J; Chaillet, Nils; Brassard, Normand; Bujold, Emmanuel

2013-03-01

To evaluate obstetric outcomes in women undergoing a trial of labor (TOL) after a previous cesarean for dystocia in second stage of labor. A retrospective cohort study of women with one previous low transverse cesarean undergoing a first TOL was performed. Women with previous cesarean for dystocia in first stage and those with previous dystocia in second stage were compared with those with previous cesarean for nonrecurrent reasons (controls). Multivariable regressions analyses were performed. Of 1655 women, those with previous dystocia in second stage of labor (n = 204) had greater risks than controls (n = 880) to have an operative delivery [odds ratio (OR): 1.5; 95% confidence intervals (CI) 1.1 to 2.2], shoulder dystocia (OR: 2.9; 95% CI 1.1 to 8.0), and uterine rupture in the second stage of labor (OR: 4.9; 95% CI 1.1 to 23), and especially in case of fetal macrosomia (OR: 29.6; 95% CI 4.4 to 202). The median second stage of labor duration before uterine rupture was 2.5 hours (interquartile range: 1.5 to 3.2 hours) in these women. Previous cesarean for dystocia in the second stage of labor is associated with second-stage uterine rupture at next delivery, especially in cases of suspected fetal macrosomia and prolonged second stage of labor. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Functional Impairment of Myeloid Dendritic Cells during Advanced Stage of HIV-1 Infection: Role of Factors Regulating Cytokine Signaling.

Directory of Open Access Journals (Sweden)

Meenakshi Sachdeva

Full Text Available Severely immunocompromised state during advanced stage of HIV-1 infection has been linked to functionally defective antigen presentation by dendritic cells (DCs. The molecular mechanisms behind DC impairment are still obscure. We investigated changes in DC function and association of key regulators of cytokine signaling during different stages of HIV-1 infection and following antiretroviral therapy (ART.Phenotypic and functional characteristics of circulating myeloid DCs (mDCs in 56 ART-naive patients (23 in early and 33 in advanced stage of disease, 36 on ART and 24 healthy controls were evaluated. Sixteen patients were studied longitudinally prior-to and 6 months after the start of ART. For functional studies, monocyte-derived DCs (Mo-DCs were evaluated for endocytosis, allo-stimulation and cytokine secretion. The expression of suppressor of cytokine signaling (SOCS-1 and other regulators of cytokine signaling was evaluated by real-time RT-PCR.The ability to respond to an antigenic stimulation was severely impaired in patients in advanced HIV-1 disease which showed partial recovery in the treated group. Mo-DCs from patients with advanced HIV-disease remained immature with low allo-stimulation and reduced cytokine secretion even after TLR-4 mediated stimulation ex-vivo. The cells had an increased expression of negative regulatory factors like SOCS-1, SOCS-3, SH2-containing phosphatase (SHP-1 and a reduced expression of positive regulators like Janus kinase (JAK2 and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB1. A functional recovery after siRNA mediated silencing of SOCS-1 in these mo-DCs confirms the role of negative regulatory factors in functional impairment of these cells.Functionally defective DCs in advanced stage of HIV-1 infection seems to be due to imbalanced state of negative and positive regulatory gene expression. Whether this is a cause or effect of increased viral replication at this stage of disease

MR staging of pelvic endometriosis. Role of fat-suppression T1-weighted images

International Nuclear Information System (INIS)

Oishi-Tanaka, Yumiko; Itai, Yuji; Anno, Izumi; Matsumoto, Kunihiko; Ebihara, Reiko; Nishida, Masato

1996-01-01

We examined whether MR can determine the stage of endometriosis according to the scoring system established and revised by the American Fertility Society (r-AFS), a system which is widely used by gynecologists. We also studied the utility of fat suppression T 1 -weighted images in improving accuracy. Seventeen patients with endometriosis examined by conventional MR were included in this study. All the patients had surgically proved stage III or IV disease. We determined the stage by MR using the following criteria according to the r-AFS system: adnexal masses without normal ovarian tissue were considered deep ovarian lesions, while those with normal tissue were considered superficial. A lack of fat between the lesion and surrounding structures was considered a dense adhesion, and hyperintense spots were considered peritoneal implants. The MR scores of patients with and without fat suppression were correlated with the surgical scores. MR staging corresponded to surgical staging in 15 of the 17 patients. In eight patients, peritoneal implants of less than 1.5 cm were depicted only by fat-suppression images. However, these lesions did not change the score significantly. MR imaging could determine the stage in advanced endometriosis. Fat-suppression could highlight smaller implants. These tiny lesions had little clinical meaning in these advanced cases; however, the clinical value of this technique should be evaluated in milder disease. (author)

Performance prediction method for a multi-stage Knudsen pump

Science.gov (United States)

Kugimoto, K.; Hirota, Y.; Kizaki, Y.; Yamaguchi, H.; Niimi, T.

2017-12-01

In this study, the novel method to predict the performance of a multi-stage Knudsen pump is proposed. The performance prediction method is carried out in two steps numerically with the assistance of a simple experimental result. In the first step, the performance of a single-stage Knudsen pump was measured experimentally under various pressure conditions, and the relationship of the mass flow rate was obtained with respect to the average pressure between the inlet and outlet of the pump and the pressure difference between them. In the second step, the performance of a multi-stage pump was analyzed by a one-dimensional model derived from the mass conservation law. The performances predicted by the 1D-model of 1-stage, 2-stage, 3-stage, and 4-stage pumps were validated by the experimental results for the corresponding number of stages. It was concluded that the proposed prediction method works properly.

A Carbohydrate Moiety of Secreted Stage-Specific Glycoprotein 4 Participates in Host Cell Invasion by Trypanosoma cruzi Extracellular Amastigotes

Science.gov (United States)

Florentino, Pilar T. V.; Real, Fernando; Orikaza, Cristina M.; da Cunha, Julia P. C.; Vitorino, Francisca N. L.; Cordero, Esteban M.; Sobreira, Tiago J. P.; Mortara, Renato A.

2018-01-01

Trypanosoma cruzi is the etiologic agent of Chagas’ disease. It is known that amastigotes derived from trypomastigotes in the extracellular milieu are infective in vitro and in vivo. Extracellular amastigotes (EAs) have a stage-specific surface antigen called Ssp-4, a GPI-anchored glycoprotein that is secreted by the parasites. By immunoprecipitation with the Ssp-4-specific monoclonal antibodies (mAb) 2C2 and 1D9, we isolated the glycoprotein from EAs. By mass spectrometry, we identified the core protein of Ssp-4 and evaluated mRNA expression and the presence of Ssp-4 carbohydrate epitopes recognized by mAb1D9. We demonstrated that the carbohydrate epitope recognized by mAb1D9 could promote host cell invasion by EAs. Although infectious EAs express lower amounts of Ssp-4 compared with less-infectious EAs (at the mRNA and protein levels), it is the glycosylation of Ssp-4 (identified by mAb1D9 staining only in infectious strains and recognized by galectin-3 on host cells) that is the determinant of EA invasion of host cells. Furthermore, Ssp-4 is secreted by EAs, either free or associated with parasite vesicles, and can participate in host-cell interactions. The results presented here describe the possible role of a carbohydrate moiety of T. cruzi surface glycoproteins in host cell invasion by EA forms, highlighting the potential of these moieties as therapeutic and vaccine targets for the treatment of Chagas’ disease. PMID:29692765

Efficacy and safety of direct-acting antivirals-based antiviral therapies for hepatitis C virus patients with stage 4-5 chronic kidney disease: a meta-analysis.

Science.gov (United States)

Li, Tao; Qu, Yundong; Guo, Ying; Wang, Yan; Wang, Lei

2017-07-01

The aim of this study was to assess the efficacy and safety of direct-acting antivirals (DAA)-based antiviral therapies for HCV patients with stage 4-5 chronic kidney disease. We conducted a systematic literature search in PubMed, EMBASE, Web of Science, and CENTRAL on the Cochrane Library without time and language limitations. The search strategy used was "(End stage renal disease OR chronic kidney failure OR severe renal impairment OR chronic kidney disease OR dialysis) AND (sofosbuvir OR simeprevir OR grazoprevir OR elbasvir OR ombitasvir OR paritaprevir OR ritonavir OR dasabuvir OR daclatasvir OR asuparevir OR direct-acting antiviral OR DAA)". Sustained virologic response at 12 weeks after the end of treatment (SVR12), adverse events (AEs) and/or serious adverse events (SAEs) with 95% confidence intervals (CI) were pooled. Eleven studies, comprising a total of 264 patients were included for our meta-analysis. The pooled SVR12 rate were 93.2% (95% CI 89.9%-95.9%, I 2 =0.0%), 89.4% (95% CI 82.0%-95.0%, I 2 =0.0%) and 94.7% (95% CI 91.0%-97.5%, I 2 =0.0%) in total population, patients with sofosbuvir-based therapies and patients with non-sofosbuvir-based therapies respectively. For HCV genotype 1 patients, the pooled SVR12 rate was 93.1% (95% CI 88.3%-96.7%, I 2 =20.0%). The pooled incidence of SAEs was 12.1% (95% CI 6.2%-19.7%, I 2 =55.0%). The pooled discontinuation rate because of AEs or SAEs in our meta-analysis was 2.2% (95% CI 0.8%-4.4%, I 2 =0.0%). DAA-based antiviral therapies are effective and well-tolerated for HCV patients with stage 4-5 chronic kidney disease. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

MRI staging of urinary bladder cancer: results using a ferrous contrastographic solution (JKA1)

International Nuclear Information System (INIS)

Giovagnoli, A.; Ercolani, P.; De Nigris, E.; Villanova, A.

1990-01-01

The authors report the results of the staging of urinary bladder cancers by means of MRI using a new ferrous contrastographic solution called JKA1. Eighteen patients with proved bladder neoplasms were examined by means of MRI: the bladder was filled with physiological solution first, and then with JKA1. Six patients were studied also after filling their bladders with Gd DTPA solution (1:50). The results show that the use of JKA1, a T2-positive contrast medium, improved MR capabilities in the evaluation of small lesions (<1cm in diameter) with minimal invasion of bladder wall; MR staging accuracy was 66.6% with the physiological solution and 77.8% with JKA1. The authors confirm the need for a wider MR study, in particular of T2 lesions (a critical subject for staging and surgical management) to assess MR diagnostic capabilities

Enhancement MRI evaluation of neuroblastoma staging in children

International Nuclear Information System (INIS)

Li Xin; Wang Chunxiang; Zhao Bin; Liu Peifang

2002-01-01

Objective: To evaluate the value and limitation of Gd-DTPA enhanced MRI for neuroblastoma staging in children. Methods: Twelve cases of neuroblastoma proved by operation or bone marrow aspiration were examined by gadolinium-enhanced MRI. The age ranged from seven months to five years, mean 3.7 years. Eight tumors originated from adrenal, and four from posterior mediastinum. Conventional sequences, double dose gadolinium-enhanced MRI, and 3D CEMRA were used in all patients. Six cases were examined by CT in same time. Imaging staging on surgic-histopathological-based International Neuroblastoma Staging System (INSS) was performed. Results: Six patients were staged by CT, including stage I-II in 2 cases, stage III in 4 cases, and stage IV in none. Twelve patients were staged by conventional MRI, including stage I-II in 2 cases, stage III in 9 cases, and stage IV in 1 case. Twelve patients were staged by double dose gadolinium-enhanced MRI, including stage I-II in 1 case, stage III in 1 case, and stage IV in 10 cases. Conclusion: Gadolinium-enhanced MRI was a single best imaging modality for neuroblastoma, most useful for distal to diaphragm metastasis, dumbbell tumor intraspinal extension, and bone marrow metastasis that was not detected by aspirate examination. Enhancement MRI was important in evaluating the therapy and was also helpful in assessing the therapeutic efficacy and relapse. 3D CEMRA helps demonstrate large vascular encasement and tumor erosion into important organs, and it is useful in assessing the respectability. Long examination time and lack in showing the characteristic calcium were the limitations

Dataset of quantitative spectral EEG of different stages of kindling acquisition in rats.

Science.gov (United States)

Jalilifar, Mostafa; Yadollahpour, Ali

2018-02-01

The data represented here are in relation with the manuscript "Quantitative assessments of extracellular EEG to classify specific features of main phases of seizure acquisition based on kindling model in Rat" (Jalilifar et al., 2017) [1] which quantitatively classified different main stages of the kindling process based on their electrophysiological characteristics using EEG signal processing. The data in the graphical form reported the contribution of different sub bands of EEG in different stages of kindling- induced epileptogenesis. Only EEG signals related to stages 1-2 (initial seizure stages (ISSs)), 3 (localized seizure stage (LSS)), and 4-5 (generalized seizure stages (GSSs) were transferred into frequency function by Fast Fourier Transform (FFT) and their power spectrum and power of each sub bands including delta (1-4 Hz), Theta (4-8 Hz), alpha (8-12 Hz), beta (12-28 Hz), gamma (28-40 Hz) were calculated with MATLAB 2013b. Accordingly, all results were obtained quantitatively which can contribute to reduce the errors in the behavioral assessments.

A germline mutation in the BRCA1 3'UTR predicts Stage IV breast cancer.

Science.gov (United States)

Dorairaj, Jemima J; Salzman, David W; Wall, Deirdre; Rounds, Tiffany; Preskill, Carina; Sullivan, Catherine A W; Lindner, Robert; Curran, Catherine; Lezon-Geyda, Kim; McVeigh, Terri; Harris, Lyndsay; Newell, John; Kerin, Michael J; Wood, Marie; Miller, Nicola; Weidhaas, Joanne B

2014-06-10

A germline, variant in the BRCA1 3'UTR (rs8176318) was previously shown to predict breast and ovarian cancer risk in women from high-risk families, as well as increased risk of triple negative breast cancer. Here, we tested the hypothesis that this variant predicts tumor biology, like other 3'UTR mutations in cancer. The impact of the BRCA1-3'UTR-variant on BRCA1 gene expression, and altered response to external stimuli was tested in vitro using a luciferase reporter assay. Gene expression was further tested in vivo by immunoflourescence staining on breast tumor tissue, comparing triple negative patient samples with the variant (TG or TT) or non-variant (GG) BRCA1 3'UTR. To determine the significance of the variant on clinically relevant endpoints, a comprehensive collection of West-Irish breast cancer patients were tested for the variant. Finally, an association of the variant with breast screening clinical phenotypes was evaluated using a cohort of women from the High Risk Breast Program at the University of Vermont. Luciferase reporters with the BRCA1-3'UTR-variant (T allele) displayed significantly lower gene expression, as well as altered response to external hormonal stimuli, compared to the non-variant 3'UTR (G allele) in breast cancer cell lines. This was confirmed clinically by the finding of reduced BRCA1 gene expression in triple negative samples from patients carrying the homozygous TT variant, compared to non-variant patients. The BRCA1-3'UTR-variant (TG or TT) also associated with a modest increased risk for developing breast cancer in the West-Irish cohort (OR=1.4, 95% CI 1.1-1.8, p=0.033). More importantly, patients with the BRCA1-3'UTR-variant had a 4-fold increased risk of presenting with Stage IV disease (p=0.018, OR=3.37, 95% CI 1.3-11.0). Supporting that this finding is due to tumor biology, and not difficulty screening, obese women with the BRCA1-3'UTR-variant had significantly less dense breasts (p=0.0398) in the Vermont cohort. A variant in

Proton Beam Therapy of Stage II and III Non–Small-Cell Lung Cancer

International Nuclear Information System (INIS)

Nakayama, Hidetsugu; Satoh, Hiroaki; Sugahara, Shinji; Kurishima, Koichi; Tsuboi, Koji; Sakurai, Hideyuki; Ishikawa, Shigemi; Tokuuye, Koichi

2011-01-01

Purpose: The present retrospective study assessed the role of proton beam therapy (PBT) in the treatment of patients with Stage II or III non–small-cell lung cancer who were inoperable or ineligible for chemotherapy because of co-existing disease or refusal. Patients and Methods: Between November 2001 and July 2008, PBT was given to 35 patients (5 patients with Stage II, 12 with Stage IIIA, and 18 with Stage IIIB) whose median age was 70.3 years (range, 47.4–85.4). The median proton dose given was 78.3 Gy (range, 67.1–91.3) (relative biologic effectiveness). Results: Local progression-free survival for Stage II-III patients was 93.3% at 1 year and 65.9% at 2 years during a median observation period of 16.9 months. Four patients (11.4%) developed local recurrence, 13 (37.1%) developed regional recurrence, and 7 (20.0%) developed distant metastases. The progression-free survival rate for Stage II-III patients was 59.6% at 1 year and 29.2% at 2 years. The overall survival rate of Stage II-III patients was 81.8% at 1 year and 58.9% at 2 years. Grade 3 or greater toxicity was not observed. A total of 15 patients (42.9%) developed Grade 1 and 6 (17.1%) Grade 2 toxicity. Conclusion: PBT for Stage II-III non–small-cell lung cancer without chemotherapy resulted in good local control and low toxicity. PBT has a definite role in the treatment of patients with Stage II-III non–small-cell lung cancer who are unsuitable for surgery or chemotherapy.

Proton Beam Therapy of Stage II and III Non-Small-Cell Lung Cancer

Energy Technology Data Exchange (ETDEWEB)

Nakayama, Hidetsugu, E-mail: hnakayam@tokyo-med.ac.jp [Proton Medical Research Center, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Department of Radiation Oncology, Tokyo Medical University, Shinjuku, Tokyo (Japan); Satoh, Hiroaki [Department of Respiratory Medicine, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Sugahara, Shinji [Proton Medical Research Center, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Department of Radiation Oncology, Tokyo Medical University, Shinjuku, Tokyo (Japan); Kurishima, Koichi [Department of Respiratory Medicine, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Tsuboi, Koji; Sakurai, Hideyuki [Proton Medical Research Center, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Ishikawa, Shigemi [Department of Thoracic Surgery, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Tokuuye, Koichi [Proton Medical Research Center, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Department of Radiation Oncology, Tokyo Medical University, Shinjuku, Tokyo (Japan)

2011-11-15

Purpose: The present retrospective study assessed the role of proton beam therapy (PBT) in the treatment of patients with Stage II or III non-small-cell lung cancer who were inoperable or ineligible for chemotherapy because of co-existing disease or refusal. Patients and Methods: Between November 2001 and July 2008, PBT was given to 35 patients (5 patients with Stage II, 12 with Stage IIIA, and 18 with Stage IIIB) whose median age was 70.3 years (range, 47.4-85.4). The median proton dose given was 78.3 Gy (range, 67.1-91.3) (relative biologic effectiveness). Results: Local progression-free survival for Stage II-III patients was 93.3% at 1 year and 65.9% at 2 years during a median observation period of 16.9 months. Four patients (11.4%) developed local recurrence, 13 (37.1%) developed regional recurrence, and 7 (20.0%) developed distant metastases. The progression-free survival rate for Stage II-III patients was 59.6% at 1 year and 29.2% at 2 years. The overall survival rate of Stage II-III patients was 81.8% at 1 year and 58.9% at 2 years. Grade 3 or greater toxicity was not observed. A total of 15 patients (42.9%) developed Grade 1 and 6 (17.1%) Grade 2 toxicity. Conclusion: PBT for Stage II-III non-small-cell lung cancer without chemotherapy resulted in good local control and low toxicity. PBT has a definite role in the treatment of patients with Stage II-III non-small-cell lung cancer who are unsuitable for surgery or chemotherapy.

Extending Metformin Use in Diabetic Kidney Disease: A Pharmacokinetic Study in Stage 4 Diabetic Nephropathy

Directory of Open Access Journals (Sweden)

Ajith Munasinghe Dissanayake

2017-07-01

Discussion: In our patient cohorts with diabetes and stage 4 chronic kidney disease, treatment with 4 weeks of low-dose metformin was not associated with adverse safety outcomes and revealed stable pharmacokinetics. Our study supports the liberalization of metformin use in this population and supports the use of metformin assays for more individualized dosing.

The prognostic value of peripheral CD4+CD25+ T lymphocytes among early stage and triple negative breast cancer patients receiving dendritic cells-cytokine induced killer cells infusion.

Science.gov (United States)

Song, Qing-Kun; Ren, Jun; Zhou, Xin-Na; Wang, Xiao-Li; Song, Guo-Hong; Di, Li-Jun; Yu, Jing; Hobeika, Amy; Morse, Michael A; Yuan, Yan-Hua; Yang, Hua-Bing; Lyerly, Herbert Kim

2015-12-01

This study aimed to assess the prognostic value of CD4+CD25+ T lymphocyte in peripheral blood among breast cancer patients treated with adoptive T lymphocytes immunotherapy. 217 patients participated in the follow-up study. CD4+CD25+ proportion was measured by flow cytometry in peripheral T cells. The median survival was estimated by Kaplan-Meier curve, Log-rank test and Cox hazard proportion regression model, between groups of CD4+CD25+ proportion more than 5% and less than or equal to 5% in peripheral T cells. Peripheral CD4+CD25+ T lymphocytes had not a relationship with progression-free survival. It was featured that above 5% peripheral CD4+CD25+ proportion of T cells was related with the median overall survival by a shorten of 51 months (p < 0.05) with the HR 1.65 (95%CI 1.04, 2.62). Above 5% CD4+CD25+proportion of T cells produced the HR to be 1.76 (95%CI 1.07, 2.87) In stage 0-II patients, and 3.59 (95%CI 1.05, 12.29) in triple negative breast cancer patients. Cellular immunity restoration recovered by adoptive T cell infusions which resulted in less proportion of peripheral CD4+CD25+T lymphocytes could be a potential prognostic indicator among early stage and triple negative patients.

A Novel Inflammation-Based Stage (I Stage Predicts Overall Survival of Patients with Nasopharyngeal Carcinoma

Directory of Open Access Journals (Sweden)

Jian-Pei Li

2016-11-01

Full Text Available Recent studies have indicated that inflammation-based prognostic scores, such as the Glasgow Prognostic Score (GPS, modified GPS (mGPS and C-reactive protein/Albumin (CRP/Alb ratio, platelet–lymphocyte ratio (PLR, and neutrophil–lymphocyte ratio (NLR, have been reported to have prognostic value in patients with many types of cancer, including nasopharyngeal carcinoma (NPC. In this study, we proposed a novel inflammation-based stage, named I stage, for patients with NPC. A retrospective study of 409 newly-diagnosed cases of NPC was conducted. The prognostic factors (GPS, mGPS, CRP/Alb ratios, PLR, and NLR were evaluated using univariate and multivariate analyses. Then, according to the results of the multivariate analyses, we proposed a I stage combination of independent risk factors (CRP/Alb ratio and PLR. The I stage was calculated as follows: patients with high levels of CRP/Alb ratio (>0.03 and PLR (>146.2 were defined as I2; patients with one or no abnormal values were defined as I1 or I0, respectively. The relationships between the I stage and clinicopathological variables and overall survival (OS were evaluated. In addition, the discriminatory ability of the I stage with other inflammation-based prognostic scores was assessed using the AUCs (areas under the curves analyzed by receiver operating characteristics (ROC curves. The p value of <0.05 was considered to be significant. A total of 409 patients with NPC were enrolled in this study. Multivariate analyses revealed that only the CRP/Alb ratio (Hazard ratio (HR = 2.093; 95% Confidence interval (CI: 1.222–3.587; p = 0.007 and PLR (HR: 2.003; 95% CI: 1.177–3.410; p = 0.010 were independent prognostic factors in patients with NPC. The five-year overall survival rates for patients with I0, I1, and I2 were 92.1% ± 2.9%, 83.3% ± 2.6%, and 63.1% ± 4.6%, respectively (p < 0.001. The I stage had a higher area under the curve value (0.670 compared with other systemic inflammation

Role of pelvic lymphadenectomy in stage 1A endometrial carcinoma ...

African Journals Online (AJOL)

Introduction: Endometrial cancer is the commonest gynecological cancer mostly affecting women in the postmenopausal age group. There is a debate regarding the need of pelvic lymphadenectomy in managing stage 1A diagnosed preoperatively, we try to evaluate this need. Objective: To evaluate the role of pelvic ...

Effects of gamma radiation on cigarette beetle. 1. Radiosensitivity of different stages of Lasioderma serricorne

International Nuclear Information System (INIS)

Maneto, E.C.; Lapis, E.B.; Parungae, A.

1976-02-01

A study was made to investigate the radiosensitivity of all the developmental stages of the cigarette beetle, Lasioderma serricorne (F.) exposed to different doses (10 to 100 krad) of gamma radiation. It was found that the effect is dependent upon the metamorphic stage and the age of the insert at any particular stage. Susceptibility of the eggs markedly decreased with age. A dose of only 10 krad was needed to completely prevent 1-day old eggs from hatching while 50 krad was required for similar effect on 4-day old eggs. However, all the hatched larvae died without transforming into pupae. First instar larvae and prepupae were killed before transforming into adult form at all dose levels. The more resistant pupae showed a higher percentage of adult emergence at 70 krad while 80 and 100 krad prevented the pupae to emerge as adults. On the other hand, it seems that irradiation did not considerably affect the longevity of the adults, since at most dosages, mortality was comparable with the control group. Using mortality alone as a criterion for measuring the sesceptibility of L. serricorne, 16,000 rads which is the recommended dose for the control of grain weevils, is ineffective for the control of adult cigarette beetles

Gender-specific differences in cancer-specific survival after radical cystectomy for patients with urothelial carcinoma of the urinary bladder in pathologic tumor stage T4a.

Science.gov (United States)

May, Matthias; Bastian, Patrick J; Brookman-May, Sabine; Fritsche, Hans-Martin; Tilki, Derya; Otto, Wolfgang; Bolenz, Christian; Gilfrich, Christian; Trojan, Lutz; Herrmann, Edwin; Moritz, Rudolf; Tiemann, Arne; Müller, Stefan C; Ellinger, Jörg; Buchner, Alexander; Stief, Christian G; Wieland, Wolf F; Höfner, Thomas; Hohenfellner, Markus; Haferkamp, Axel; Roigas, Jan; Zacharias, Mario; Nuhn, Philipp; Burger, Maximilian

2013-10-01

Bladder cancer (UCB) staged pT4a show heterogeneous outcome after radical cystectomy (RC). No risk model has been established to date. Despite gender-specific differences, no comparative studies exist for this tumor stage. Cancer-specific survival (CSS) of 245 UCB patients without neoadjuvant chemotherapy staged pT4a, pN0-2, M0 after RC were analyzed in a retrospective multi-center study. Seventeen patients were excluded from further analysis due to carcinoma in situ (CIS) of the prostatic urethra and/or positive surgical margins. Average follow-up period was 30 months (IQR: 14-45). The influence of different clinical and histopathologic variables on CSS was determined through uni- and multivariate Cox regression analyses. Two risk groups were generated using factors with independent effect in multivariate models. Internal validity of the prediction model was evaluated by bootstrapping. Eighty-four percent of the patients (n = 192) were male; 72% (n = 165) showed lymphovascular invasion (LVI). The 5-year CSS rate was 31%, and significantly different between male and female (35% vs. 15%, P = 0.003). Multivariate Cox regression modeling, female gender (HR = 1.83, P = 0.008), LVI (HR = 1.92, P = 0.005), and absence of adjuvant chemotherapy (HR = 0.61, P = 0.020) significantly worsened CSS. Two risk groups were generated using these 3 criteria, which differed significantly between each other in CSS (5-year-CSS: 46% vs. 12%, P < 0.001). The c-index value of the risk model was 0.61 (95% CI: 0.53-0.68, P < 0.001). Prognosis in UCB staged pT4a is heterogeneous. Female gender and LVI are adverse factors. Adjuvant chemotherapy seems to improve outcome. The present analysis establishes the first risk model for this demanding tumor stage. Copyright © 2013 Elsevier Inc. All rights reserved.

SYNTHESIS, CHARACTERIZATION AND ANTIOXIDANT ACTIVITIES OF NOVEL 1-(MORPHOLINE-4-YL-METHYL-3-ALKYL(ARYL-4-[4-(DIMETHYLAMINO-BENZYLIDENAMINO]-4,5-DIHYDRO-1H-1,2,4-TRIAZOL-5-ONES

Directory of Open Access Journals (Sweden)

Özlem Gürsoy Kol

2016-08-01

Full Text Available In this paper, eight novel 1-(morpholine-4-yl-methyl-3-alkyl(aryl-4-[4-(dimethylamino-benzylidenamino]-4,5-dihydro-1H-1,2,4-triazol-5-ones (2 were obtained by the reactions of 3-alkyl(aryl-4-[4-(dimethylamino-benzylidenamino]-4,5-dihydro-1H-1,2,4-triazol-5-ones (1 with formaldehyde and morpholine. The novel synthesized compounds were identified by IR, 1H NMR and 13C NMR spectral data. Besides, the newly synthesized compounds were analysed for their in vitro potential antioxidant capacities in three different assays. All of the compounds demonstrated significant activity for metal chelating effect.

Unusual fatty metamorphosis observed in diffuse liver metastases of stage 4S neuroblastoma

Energy Technology Data Exchange (ETDEWEB)

Tazoe, Jun; Okuyama, Chio; Nishimura, Tsunehiko [Kyoto Prefectural University of Medicine, Department of Radiology, Graduate School of Medical Science, Kyoto City (Japan); Iehara, Tomoko; Hosoi, Hajime [Kyoto Prefectural University of Medicine, Department of Paediatrics, Graduate School of Medical Science, Kyoto City (Japan)

2010-05-15

We report a case of stage 4S neuroblastoma in which CT showed diffuse liver metastases containing a geographical fatty area in the periportal region. MRI showed this abnormality to correspond to an area with an unusual pattern of fatty change. {sup 123}I-metaiodobenzylguanidine (MIBG) scintigraphy demonstrated increased accumulation throughout the liver, except for the region showing fatty change. To the best of our knowledge, this is the first report of liver metastases from neuroblastoma with geographical fatty infiltration. (orig.)

Unusual fatty metamorphosis observed in diffuse liver metastases of stage 4S neuroblastoma

International Nuclear Information System (INIS)

Tazoe, Jun; Okuyama, Chio; Nishimura, Tsunehiko; Iehara, Tomoko; Hosoi, Hajime

2010-01-01

We report a case of stage 4S neuroblastoma in which CT showed diffuse liver metastases containing a geographical fatty area in the periportal region. MRI showed this abnormality to correspond to an area with an unusual pattern of fatty change. 123 I-metaiodobenzylguanidine (MIBG) scintigraphy demonstrated increased accumulation throughout the liver, except for the region showing fatty change. To the best of our knowledge, this is the first report of liver metastases from neuroblastoma with geographical fatty infiltration. (orig.)

Survival Advantage Associated with Decrease in Stage at Detection from Stage IIIC to Stage IIIA Epithelial Ovarian Cancer

Science.gov (United States)

Lefringhouse, Jason; Pavlik, Edward; Miller, Rachel; DeSimone, Christopher; Ueland, Frederick; Kryscio, Richard; van Nagell, J. R.

2014-01-01

Objective. The aim of this study was to document the survival advantage of lowering stage at detection from Stage IIIC to Stage IIIA epithelial ovarian cancer. Methods. Treatment outcomes and survival were evaluated in patients with Stage IIIA and Stage IIIC epithelial ovarian cancer treated from 2000 to 2009 at the University of Kentucky Markey Cancer Center (UKMCC) and SEER institutions. Results. Cytoreduction to no visible disease (P < 0.0001) and complete response to platinum-based chemotherapy (P < 0.025) occurred more frequently in Stage IIIA than in Stage IIIC cases. Time to progression was shorter in patients with Stage IIIC ovarian cancer (17 ± 1 months) than in those with Stage II1A disease (36 ± 8 months). Five-year overall survival (OS) improved from 41% in Stage IIIC patients to 60% in Stage IIIA patients treated at UKMCC and from 37% to 56% in patients treated at SEER institutions for a survival advantage of 19% in both data sets. 53% of Stage IIIA and 14% of Stage IIIC patients had NED at last followup. Conclusions. Decreasing stage at detection from Stage IIIC to stage IIIA epithelial ovarian cancer is associated with a 5-year survival advantage of nearly 20% in patients treated by surgical tumor cytoreduction and platinum-based chemotherapy. PMID:25254047

Conditional cancer-specific mortality in T4, N1, or M1 prostate cancer: implications for long-term prognosis

International Nuclear Information System (INIS)

Muralidhar, Vinayak; Mahal, Brandon A.; Nguyen, Paul L.

2015-01-01

The risk of prostate cancer-specific mortality (PCSM) following a diagnosis of prostate cancer may improve after patients have survived a number of years after diagnosis. We sought to determine long-term conditional PCSM for patients with stage T4, N1, or M1 prostate cancer. We identified 66,817 patients diagnosed with stage IV (T4N0M0, N1M0, or M1) prostate cancer between 1973 and 2011 using the Surveillance, Epidemiology, and End Results (SEER) database. Conditional five-year PCSM was evaluated for each group of patients at 5, 10, and 15 years of survival according to the Fine & Gray model for competing risks after adjusting for tumor grade, age, income level, and marital status. Race-stratified analyses were also performed. There were 13,345 patients with T4 disease, 12,450 patients with N1 disease, and 41,022 patients with M1 disease. Median follow-up among survivors in the three groups was 123 months (range: 0–382 months), 61 months (range: 0–410 months), and 30 months (range: 0–370 months), respectively. Conditional PCSM improved in all three groups over time. Among patients with T4 disease, 5-year PCSM improved from 13.9 % at diagnosis to 11.2, 8.1, and 6.5 % conditioned on 5, 10, or 15 years of survival, respectively (p < 0.001 in all cases). In patients with N1 disease, 5-year PCSM increased within the first five years and decreased thereafter, from 18.9 % at diagnosis to 21.4 % (p < 0.001), 17.6 % (p = 0.055), and 13.8 % (p < 0.001), respectively. In patients with metastatic disease, 5-year PCSM improved from 57.2 % at diagnosis to 41.1, 28.8, and 20.8 %, respectively (p < 0.001). White race was associated with a greater increase in conditional survival compared to non-white race among those with T4 or N1 disease. While patients with T4, N1, or M1 prostate cancer are never “cured,” their odds of cancer-specific survival increase substantially after they have survived for 5 or more years. Physicians who take care of patients with prostate cancer

Improvement of two-stage GM refrigerator performance using a hybrid regenerator

International Nuclear Information System (INIS)

Ke, G.; Makuuchi, H.; Hashimoto, T.; Onishi, A.; Li, R.; Satoh, T.; Kanazawa, Y.

1994-01-01

To improve the performance of two-stage GM refrigerators, a hybrid regenerator with magnetic materials of Er 3 Ni and ErNi 0.9 Co 0.1 was used in the 2nd stage regenerator because of its large heat exchange capacity. The largest refrigeration capacity achieved with the hybrid regenerator was 0.95W at helium liquefied temperature of 4.2K. This capacity is 15.9% greater than the 0.82W refrigerator with only Er 3 Ni as the 2nd regenerator material. Use of the hybrid regenerator not only increases the refrigeration capacity at 4.2K, but also allows the 4K GM refrigerator to be used with large 1st stage refrigeration capacity, thus making it more practical

Two-Stage Surgery for a Large Cervical Dumbbell Tumour in Neurofibromatosis 1: A Case Report

Directory of Open Access Journals (Sweden)

Mohd Ariff S

2011-11-01

Full Text Available Spinal neurofibromas occur sporadically and typically occur in association with neurofibromatosis 1. Patients afflicted with neurofibromatosis 1 usually present with involvement of several nerve roots. This report describes the case of a 14- year-old child with a large intraspinal, but extradural tumour with paraspinal extension, dumbbell neurofibroma of the cervical region extending from the C2 to C4 vertebrae. The lesions were readily detected by MR imaging and were successfully resected in a two-stage surgery. The time interval between the first and second surgery was one month. We provide a brief review of the literature regarding various surgical approaches, emphasising the utility of anterior and posterior approaches.

DPP4 inhibitors promote biological functions of human endothelial progenitor cells by targeting the SDF-1/CXCR4 signaling pathway

Directory of Open Access Journals (Sweden)

Liu Feng

2016-01-01

Full Text Available Dipeptidyl peptidase 4 (DPP4 inhibitors(oral hypoglycemic agentshave beneficial effects during the early stages of diabetes. In this study, we evaluated the role of DPP4inhibitorsonthe biological functions of cultured human endothelial progenitor cells (EPCs. After treating EPCs with the DPP4 inhibitors sitagliptin and vildagliptin, we examined the mRNA expression of DPP4, vascular endothelial growth factor (VEGF,VEGF receptor 2 (VEGFR-2,endothelial nitric oxide synthase (eNOS, caspase-3,stromal cell-derived factor-1 (SDF-1, chemokine (C-X-C motif receptor 4 (CXCR4 were measured by RT-PCR. The protein expression of SDF-1 and CXCR4 was determined by Western blot; cell proliferation was tested by the MTT method, and DPP4 activity was determined by a DPP4 assay. Our results revealed that DPP4 expression and activity were inhibited following the treatment with various doses of DPP4 inhibitors. Cell proliferation and the expression of VEGF, VEGFR-2andeNOS were up regulated, while cell apoptosis was inhibited by DPP4 inhibitors in a dose-dependent manner. DPP4 inhibitors activated the SDF-1/CXCR4 signaling pathway, shown by the elevated expression of SDF-1/CXCR4. This further proved that after the SDF-1/CXCR4 signaling pathway was blocked by its inhibitor ADM3100, the effects of DPP4 inhibitors on the proliferation and apoptosis, and the expression of VEGF, VEGFR-2and eNOS of EPCs were significantly reduced. These findings suggest that DPP4 inhibitors promote the biological functions of human EPCs by up regulating the SDF-1/CXCR4 signaling pathway.

IgG isotypic antibodies to crude Plasmodium falciparum blood-stage ...

African Journals Online (AJOL)

Methods: Levels of IgG (IgG1-IgG4) and IgM to crude P. falciparum blood stage antigen ... dosage influenced P. falciparum-specific isotypic antibody responses to blood stage .... exposed Swedish donors. ..... with adverse pregnancy outcomes.

Sensitivity of the different developmental stages of Callosobruchus maculatus to gamma irradiation

International Nuclear Information System (INIS)

Olaifa, J.I.; Adebayo, T.A.; Adesanmi, C.A.; Salau, A.M.

1990-01-01

Life stages of the cowpea seed beetle (Callosobruchus maculatus F.) were γ irradiated from a 60 Co source. Arrested development was observed at dosages of 1.0, 4.0, 10.0 and 10.0 Gy in the egg, 1st, 2nd, 3rd and 4th larvae stages respectively while 4.0 Gy induced sterility. Longevity of 2-day old adults was not affected by irradiation of 100 Gy. Preservation of cowpeas by irradiation is discussed. (author)

A NEW METHOD FOR PREPARING 6-NITRO-2-(4-BOC-PIPERAZIN-1-YL-3H-QUINAZOLIN-4-ONE

Directory of Open Access Journals (Sweden)

A. Yu. Kornylov

2017-11-01

Full Text Available The 2-amino-3H-quinazolin-4-one scaffold is found in a large number of molecules with physiological significance and pharmaceutical utility. Previously we synthesized a series of potent antagonists of fibrinogen receptor, derivatives of 2-(piperazin-1-yl-3H-quinazolin-4-one. The key building block for preparing the above series of compounds is 6-amino-2-(4-Boc-piperazin-1-yl-3H-quinazolin-4-one, which was synthesized by hydrogenation of 6-nitro-2-(4-Boc-piperazin-1-yl-3H-quinazolin-4-one. In turn, the nitro derivative was obtained starting from isatoic anhydride in four stages, by a method that can be considered classical, but difficult. The purpose of this work is to simplify the preparation of 6-nitro-2-(4-Boc-piperazin-1-yl-3H-quinazolin-4-one. We proposed an effective method for the synthesis of 6-nitro-2-(4-Boc-piperazin-1-yl-3H-quinazolin-4-one based on a sequential process, C-N cross-coupling and intramolecular amidation. As the arylhalogenide, 2-bromo-5-nitrobenzoic acid methyl ester was used, as the N-nucleophile, 4-Boc-piperazine-1-carboxamidine, a guanidine derivative, was used. In the study, we used two types of catalytic systems, which both gave good results. The application of the third generation of Palladacycleprecatalyst –[(4,5-Bis(diphenylphosphino-9,9-dimethylxanthene-2-(2′-amino-1,1′-biphenyl] palladium(II methanesulfonate, leads to the production of the target product in a high yield, in comparison with the use of the catalytic system: precatalyst – Tris(dibenzylideneacetone dipalladium(0 chloroform adduct and Buchwald Ligands – 4,5-Bis(diphenylphosphino-9,9-dimethylxanthene. The structure of the title compound was confirmed by spectroscopy 1H and 13C NMR, and FAB mass spectrometry methods, purity was controlled by HPLC. This method has potential implications for the design of various 2-amino-3H-quinazolin-4-ones.

Is Radiotherapy Necessary for Stage 1 Testicular Seminoma?

International Nuclear Information System (INIS)

Lee, Jung Ae; Park, Won; Lim, Do Hoon; Ahn, Yong Chan; Huh, Seung Jae; Yu, Jeong Il; Choi, Han Yong; Lee, Hyun Moo; Cho, Eun Yoon

2009-01-01

To report on the clinical outcome of patients with stage I testicular seminoma by postoperative radiotherapy (PORT) or surveillance after radical inguinal orchiectomy. This study is a retrospective review of 32 stage I pure seminoma patients treated between 1996 and 2005 at the Samsung Medical Center. Twenty two of the patients were treated by PORT, which was directed at the paraaortic lymphatics with a median dose of 25.2 Gy in 14 fractions for 3 weeks. The 10 remaining patients were managed by surveillance. The median follow-up period was 96 months with a range of 24 to 155 months. Clinically, most patients presented with a testicular mass or discomfort. Two of the patients had a history of undescended testes. Pathologically, 23 of the patients had intratubular germ cell neoplasia with seminoma. Both recurrence-free survival (RFS) and overall survival (OS) rates of patients treated by PORT were 100%. In the control group, 1 of the 10 patients suffered a para-aortic lymph node relapse. The RFS and OS rates of the surveillance group were 88.9% and 100%, respectively. No difference in survival was observed between the two groups. Moreover, symptom recurrence was only observed in 1 patient in the control group. The use of PORT may reduce the risk of relapse. With the availability of effective diagnostic and salvage modalities, surveillance monitoring may be considered for patients in good compliance

[Changes in mineral metabolism in stage 3, 4, and 5 chronic kidney disease (not on dialysis)].

Science.gov (United States)

Lorenzo Sellares, V; Torregrosa, V

2008-01-01

replacement therapy or with advanced chronic kidney disease. It is indicated in patients with fractures or risk factors for osteoporosis. Bone biopsy: The "gold standard" for diagnosis of bone disease. With improved knowledge of the value of noninvasive parameters, its use is infrequent. Pathological fractures in the presence or absence of minor trauma. Symptomatic patients in the presence of incongruent clinical parameters. A typical case is the presence of unexplained hypercalcemia from systemic disease, with inconclusive serum PTH values (between 120-450 pg/mL as an estimated range). Evaluation and follow-up of cardiovascular calcifications There are no consensuated clinical practice guidelines for the evaluation and follow-up of extraosseal calcifications in CKD. The clinical tools for evaluation and follow-up of cardiovascular disease are used based on clinical judgment. The periodicity of follow-up has not been established . 3. Recommended biochemical values The biochemical values recommended in clinical practice guidelines for the evaluation of bone mineral metabolism are summarized in Figure 3. The recommended PTH values do not fully coincide with the K/DOQI guidelines. The wide variability in PTH values depending on the assays used has led us to expand the recommended PTH range in stage 3 and 4 CKD. 4. Treatment 4.1. Diet. The recommended diet for the patient with CKD is traditionally based on protein restriction and phosphorus restriction for control of mineral metabolism. A favorable circumstance is that there is a close relationship between protein and phosphorus intake. In CKD stages 3, 4 and 5, it is recommended to restrict phosphorus intake to between 0.8-1 g/day when serum levels of phosphorus and PTH are above the recommended range. This is approximately equivalent to a diet of 50-60 g of protein. This reasonable antiproteinuric strategy that also restricts phosphorus intake is nutritionally safe. What should we tell them to eat? In a practical and

The expression of chemokine receptors CXCR3 and CXCR4 in predicting postoperative tumour progression in stages I-II colon cancer: a retrospective study.

Science.gov (United States)

Du, Changzheng; Yao, Yunfeng; Xue, Weicheng; Zhu, Wei-Guo; Peng, Yifan; Gu, Jin

2014-01-01

The prognostic significance of chemokine receptors in stage I/II colon cancer is unclear. We assessed the prognostic value of chemokine receptor CXCR3 and CXCR4 in stage I/II colon cancer. 145 patients with stage I/II colon cancer who underwent curative surgery alone from 2000 to 2007 were investigated. Chemokine receptor expression was assessed by immunohistochemistry. The associations between CXCR3, CXCR4 and clinicopathological variables were analysed using the χ2 test, and the relationships between chemokine receptors and a 5-year disease-free survival were analysed by univariate and multivariate analyses. The high-expression rates of CXCR3 and CXCR4 were 17.9% (26/145) and 38.6% (56/145), respectively. There were no significant associations between the expressions of CXCR3, CXCR4 and clinicopathological factors including gender, age, tumour location, histological differentiation, pathological stage, lymphovascular invasion and pretreatment serum carcinoembryonic antigen (CEA). The 5-year disease-free survival was not significantly different between low-expression groups and high-expression groups of CXCR3 and CXCR4. Multivariate analysis revealed that serum CEA and a number of retrieved lymph nodes, rather than chemokine receptors, were independent prognosticators. CXCR3 and CXCR4 are not independent prognosticators for stage I/II colon cancer after curative surgery.

A Carbohydrate Moiety of Secreted Stage-Specific Glycoprotein 4 Participates in Host Cell Invasion by Trypanosoma cruzi Extracellular Amastigotes

Directory of Open Access Journals (Sweden)

Pilar T. V. Florentino

2018-04-01

Full Text Available Trypanosoma cruzi is the etiologic agent of Chagas’ disease. It is known that amastigotes derived from trypomastigotes in the extracellular milieu are infective in vitro and in vivo. Extracellular amastigotes (EAs have a stage-specific surface antigen called Ssp-4, a GPI-anchored glycoprotein that is secreted by the parasites. By immunoprecipitation with the Ssp-4-specific monoclonal antibodies (mAb 2C2 and 1D9, we isolated the glycoprotein from EAs. By mass spectrometry, we identified the core protein of Ssp-4 and evaluated mRNA expression and the presence of Ssp-4 carbohydrate epitopes recognized by mAb1D9. We demonstrated that the carbohydrate epitope recognized by mAb1D9 could promote host cell invasion by EAs. Although infectious EAs express lower amounts of Ssp-4 compared with less-infectious EAs (at the mRNA and protein levels, it is the glycosylation of Ssp-4 (identified by mAb1D9 staining only in infectious strains and recognized by galectin-3 on host cells that is the determinant of EA invasion of host cells. Furthermore, Ssp-4 is secreted by EAs, either free or associated with parasite vesicles, and can participate in host-cell interactions. The results presented here describe the possible role of a carbohydrate moiety of T. cruzi surface glycoproteins in host cell invasion by EA forms, highlighting the potential of these moieties as therapeutic and vaccine targets for the treatment of Chagas’ disease.

Consumption of High-Polyphenol Dark Chocolate Improves Endothelial Function in Individuals with Stage 1 Hypertension and Excess Body Weight

Directory of Open Access Journals (Sweden)

Lívia de Paula Nogueira

2012-01-01

Full Text Available Background. Hypertension and excess body weight are important risk factors for endothelial dysfunction. Recent evidence suggests that high-polyphenol dark chocolate improves endothelial function and lowers blood pressure. This study aimed to evaluate the association of chocolate 70% cocoa intake with metabolic profile, oxidative stress, inflammation, blood pressure, and endothelial function in stage 1 hypertensives with excess body weight. Methods. Intervention clinical trial includes 22 stage 1 hypertensives without previous antihypertensive treatment, aged 18 to 60 years and presents a body mass index between 25.0 and 34.9 kg/m2. All participants were instructed to consume 50 g of chocolate 70% cocoa/day (2135 mg polyphenols for 4 weeks. Endothelial function was evaluated by peripheral artery tonometry using Endo-PAT 2000 (Itamar Medical. Results. Twenty participants (10 men completed the study. Comparison of pre-post intervention revealed that (1 there were no significant changes in anthropometric parameters, percentage body fat, glucose metabolism, lipid profile, biomarkers of inflammation, adhesion molecules, oxidized LDL, and blood pressure; (2 the assessment of endothelial function through the reactive hyperemia index showed a significant increase: 1.94 ± 0.18 to 2.22 ± 0.08, P=0.01. Conclusion.In individuals with stage 1 hypertension and excess body weight, high-polyphenol dark chocolate improves endothelial function.

Interactions between Bmp-4 and Msx-1 act to restrict gene expression to odontogenic mesenchyme.

Science.gov (United States)

Tucker, A S; Al Khamis, A; Sharpe, P T

1998-08-01

Tooth development is regulated by a reciprocal series of epithelial-mesenchymal interactions. Bmp4 has been identified as a candidate signalling molecule in these interactions, initially as an epithelial signal and then later at the bud stage as a mesenchymal signal (Vainio et al. [1993] Cell 75:45-58). A target gene for Bmp4 signalling is the homeobox gene Msx-1, identified by the ability of recombinant Bmp4 protein to induce expression in mesenchyme. There is, however, no evidence that Bmp4 is the endogenous inducer of Msx-1 expression. Msx-1 and Bmp-4 show dynamic, interactive patterns of expression in oral epithelium and ectomesenchyme during the early stages of tooth development. In this study, we compare the temporal and spatial expression of these two genes to determine whether the changing expression patterns of these genes are consistent with interactions between the two molecules. We show that changes in Bmp-4 expression precede changes in Msx-1 expression. At embryonic day (E)10.5-E11.0, expression patterns are consistent with BMP4 from the epithelium, inducing or maintaining Msx-1 in underlying mesenchyme. At E11.5, Bmp-4 expression shifts from epithelium to mesenchyme and is rapidly followed by localised up-regulation of Msx-1 expression at the sites of Bmp-4 expression. Using cultured explants of developing mandibles, we confirm that exogenous BMP4 is capable of replacing the endogenous source in epithelium and inducing Msx-1 gene expression in mesenchyme. By using noggin, a BMP inhibitor, we show that endogenous Msx-1 expression can be inhibited at E10.5 and E11.5, providing the first evidence that endogenous Bmp-4 from the epithelium is responsible for regulating the early spatial expression of Msx-1. We also show that the mesenchymal shift in Bmp-4 is responsible for up-regulating Msx-1 specifically at the sites of future tooth formation. Thus, we establish that a reciprocal series of interactions act to restrict expression of both genes to future

Crystal structure of 4,4′-bis[3-(piperidin-1-ylprop-1-yn-1-yl]-1,1′-biphenyl

Directory of Open Access Journals (Sweden)

Anqi Walbaum

2017-06-01

Full Text Available The title compound, C28H32N2, (I, is one of a second generation of compounds designed and synthesized based on a very potent and selective α9α10 nicotinic acetylcholine receptor antagonist ZZ161C {1,1′-[[1,1′-biphenyl]-4,4′-diylbis(prop-2-yne-3,1-diyl]bis(3,4-dimethylpyridin-1-ium bromide}, which has shown analgesic effects in a chemotherapy-induced neuropathy animal model. Compound (I was synthesized by the reaction of 4,4′-bis(3-bromoprop-1-yn-1-yl-1,1′-biphenyl with piperidine at room temperature in acetonitrile. The single-crystal used for X-ray analysis was obtained by dissolving (I in a mixture of dichloromethane and methanol, followed by slow evaporation of the solvent. In the crystal of (I, the biphenyl moiety has a twisted conformation, with a dihedral angle of 25.93 (4° between the benzene rings. Both piperidine head groups in (I are in the chair conformation and are oriented so that the N-atom lone pairs of each piperidine group point away from the central biphenyl moiety.

Combining evidence from multiple electronic health care databases: performances of one-stage and two-stage meta-analysis in matched case-control studies.

Science.gov (United States)

La Gamba, Fabiola; Corrao, Giovanni; Romio, Silvana; Sturkenboom, Miriam; Trifirò, Gianluca; Schink, Tania; de Ridder, Maria

2017-10-01

Clustering of patients in databases is usually ignored in one-stage meta-analysis of multi-database studies using matched case-control data. The aim of this study was to compare bias and efficiency of such a one-stage meta-analysis with a two-stage meta-analysis. First, we compared the approaches by generating matched case-control data under 5 simulated scenarios, built by varying: (1) the exposure-outcome association; (2) its variability among databases; (3) the confounding strength of one covariate on this association; (4) its variability; and (5) the (heterogeneous) confounding strength of two covariates. Second, we made the same comparison using empirical data from the ARITMO project, a multiple database study investigating the risk of ventricular arrhythmia following the use of medications with arrhythmogenic potential. In our study, we specifically investigated the effect of current use of promethazine. Bias increased for one-stage meta-analysis with increasing (1) between-database variance of exposure effect and (2) heterogeneous confounding generated by two covariates. The efficiency of one-stage meta-analysis was slightly lower than that of two-stage meta-analysis for the majority of investigated scenarios. Based on ARITMO data, there were no evident differences between one-stage (OR = 1.50, CI = [1.08; 2.08]) and two-stage (OR = 1.55, CI = [1.12; 2.16]) approaches. When the effect of interest is heterogeneous, a one-stage meta-analysis ignoring clustering gives biased estimates. Two-stage meta-analysis generates estimates at least as accurate and precise as one-stage meta-analysis. However, in a study using small databases and rare exposures and/or outcomes, a correct one-stage meta-analysis becomes essential. Copyright © 2017 John Wiley & Sons, Ltd.

40 CFR 721.7160 - 2-Oxepanone, polymer with 4,4′-(1-methylethylidene)bisphenol and 2,2-[(1-methylethylidene)bis(4,1...

Science.gov (United States)

2010-07-01

...-methylethylidene)bisphenol and 2,2-[(1-methylethylidene)bis(4,1-phe-ny-lene-oxy-methyl-ene)]-bi-sox-i- rane, graft... Substances § 721.7160 2-Oxepanone, polymer with 4,4′-(1-methylethylidene)bisphenol and 2,2-[(1... new uses subject to reporting. (1) The chemical substance 2-oxepanone, polymer with 4,4′(1-meth-yl-eth...

Risk Factors for Complications Differ Between Stages of Tissue-Expander Breast Reconstruction.

Science.gov (United States)

Lovecchio, Francis; Jordan, Sumanas W; Lim, Seokchun; Fine, Neil A; Kim, John Y S

2015-09-01

Tissue-expander (TE) placement followed by implant exchange is currently the most popular method of breast reconstruction. There is a relative paucity of data demonstrating patient factors that predict complications specifically by stage of surgery. The present study attempts to determine what complications are most likely to occur at each stage and how the risk factors for complications vary by stage of reconstruction. A retrospective chart review was performed on all 1275 patients who had TEs placed by the 2 senior authors between 2004 and 2013. Complication rates were determined at each stage of reconstruction, and these rates were further compared between patients who had pre-stage I radiation, post-stage I radiation, and no radiation exposure. Multivariate logistic regression was used to identify independent predictors of complications at each stage of reconstruction. A total of 1639 consecutive TEs were placed by the senior authors during the study period. The overall rate for experiencing a complication at any stage of surgery was 17%. Complications occurred at uniformly higher rates during stage I for all complications (92% stage I vs 7% stage II vs 1% stage III, P higher intraoperative percent fill (OR, 3.3; 95% CI, 1.7-6.3). Post-stage I radiation was the only independent risk factor for a stage II complication (OR, 4.5; 95% CI, 1.4-15.2). Complications occur at higher rates after stage I than after stage II, and as expected, stage III complications are exceedingly rare. Risk factors for stage I complications are different from risk factors for stage II complications. Body mass index and smoking are associated with complications at stage I, but do not predict complications at stage II surgery. The stratification of risk factors by stage of surgery will help surgeons and patients better manage both risk and expectations.

4,4′-([4,4′-Bipyridine]-1,1′-diium-1,1′-diyldibenzoate dihydrate

Directory of Open Access Journals (Sweden)

Mark A. Rodriguez

2016-06-01

Full Text Available We report here the synthesis of a neutral viologen derivative, C24H16N2O4·2H2O. The non-solvent portion of the structure (Z-Lig is a zwitterion, consisting of two positively charged pyridinium cations and two negatively charged carboxylate anions. The carboxylate group is almost coplanar [dihedral angle = 2.04 (11°] with the benzene ring, whereas the dihedral angle between pyridine and benzene rings is 46.28 (5°. The Z-Lig molecule is positioned on a center of inversion (Fig. 1. The presence of the twofold axis perpendicular to the c-glide plane in space group C2/c generates a screw-axis parallel to the b axis that is shifted from the origin by 1/4 in the a and c directions. This screw-axis replicates the molecule (and solvent water molecules through space. The Z-Lig molecule links to adjacent molecules via O—H...O hydrogen bonds involving solvent water molecules as well as intermolecular C—H...O interactions. There are also π–π interactions between benzene rings on adjacent molecules.

Assessment of skeletal maturation using mandibular second molar maturation stages.

Science.gov (United States)

Goyal, S; Goyal, S; Gugnani, N

2014-01-01

To investigate the relationship between cervical vertebrae maturation and mandibular second molar calcification stages. The study was designed as a retrospective, descriptive and crosssectional research project. Pre-treatment lateral cephalograms and panoramic radiographs of 99 males and 110 females in the age range of 7 to 18 years 7 months were evaluated with Demirjian Index (DI) and cervical vertebrae maturation indicators (CVMI) of Hassel and Farman. A null hypothesis was proposed that there is no relation between CVMI and DI. A highly significant association (Pearson's contingency coefficient 0.713 for males and 0.863 for females) was found between DI and CVMI. In males, the DI stage E corresponded to stage 2 of CVMI (pre-peak of pubertal growth spurt) and DI stages F and G corresponded to stages 3 and 4 of CVMI (peak of pubertal growth spurt). DI stage H was associated with stages 5 and 6 of CVMI (end of pubertal growth spurt). In females, the DI stages C, D corresponded to CVMI stages 1, 2; DI stages E, F with CVMI stages 3, 4; DI stages G, H with CVMI stages 5, 6. Mandibular second molar calcification stages can be used as indicators for assessment of skeletal maturity.

Adjuvant chemotherapy for elderly patients with stage I non-small-cell lung cancer ≥4 cm in size: an SEER-Medicare analysis.

Science.gov (United States)

Malhotra, J; Mhango, G; Gomez, J E; Smith, C; Galsky, M D; Strauss, G M; Wisnivesky, J P

2015-04-01

The role of adjuvant chemotherapy for non-small-cell lung cancer (NSCLC) stage I patients with tumors size ≥4 cm is not well established in the elderly. We identified 3289 patients with stage I NSCLC (T2N0M0 and tumor size ≥4 cm) who underwent lobectomy from the Surveillance, Epidemiology and End Results (SEER)-Medicare linked database diagnosed from 1992 to 2009. Overall survival and rates of serious adverse events (defined as those requiring admission to hospital) were compared between patients treated with resection alone, platinum-based adjuvant chemotherapy, or postoperative radiation (PORT) with or without adjuvant chemotherapy. Propensity scores for receiving each treatment were calculated and survival analyses were conducted using inverse probability weights based on the propensity score. Overall, 84% patients were treated with resection alone, 9% received platinum-based adjuvant chemotherapy, and 7% underwent PORT with or without adjuvant chemotherapy. Adjusted analysis showed that adjuvant chemotherapy [hazard ratio (HR), 0.82; 95% confidence interval (CI) 0.68-0.98] was associated with improved survival compared with resection alone. Conversely, the use of PORT with or without adjuvant chemotherapy (HR 1.91; 95% CI 1.64-2.23) was associated with worse outcomes. Patients receiving adjuvant chemotherapy had more serious adverse events compared with those treated with resection alone, with neutropenia (odds ratio, 21.2; 95% CI 5.8-76.6) being most significant. No significant difference was observed in rates of fever, cytopenias, nausea, and renal dysfunction. Platinum-based adjuvant chemotherapy is associated with reduced mortality and increased serious adverse events in elderly patients with stage I NSCLC and tumor size ≥4 cm. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Surgical treatment of advanced stage Freiberg disease

Directory of Open Access Journals (Sweden)

Emin Özkul

2014-09-01

Full Text Available Objective: Freiberg disesase is an avascular necrosis of the 2nd and 3rd metatarsal head and which kind of surgical option to be used is controversial in symptomatic patients. In this study the results of the advanced stage Freiberg’s disease patients, who were treated with surgery were evaluated. Methods: 12 patients (8 female, 4 male whose pain could not be solved with conservative method and underwent surgery (6 debridement, 3 osteotomy, 3 excision of the metatarsal head were included in this study. Themean age of the patients 19.1 (range 13- 31 and the mean follow-up 30.8(range 25-94 months. According to the Smillie classification 3 patients had type 5, 8 patients had type 4 and 1 patient had type 3 osteonecrosis. The results of the patients were evaluated according to Lesser Metatarsophalangeal-Interphalangeal Scale. Results: According to Lesser MetatarsophalangealInterphalangeal Scale 3 patients (%25 had excellent, 6 patients (%50 had good and 3 patients had poor results were obtained. 2 of 3 patients with poor results were type 5, and 1 patient was type 4 and all three patients underwent joint debridement. Conclusion:The method of surgical treatment of Freiberg disease determined according to the stage of the disease. Debridement alone in the treatment of patients with late stage is not enough, it should be combined with other methods.

Interferon lambda 4 (IFNL4 gene polymorphism is associated with spontaneous clearance of HCV in HIV-1 positive patients

Directory of Open Access Journals (Sweden)

Camila Fernanda da Silveira Alves

Full Text Available Abstract Approximately one-third of the individuals infected with human immunodeficiency virus type 1 (HIV-1 are co-infected with hepatitis C virus (HCV. Co-infected patients have an increased risk for developing end-stage liver diseases. Variants upstream of the IFNL3 gene have been associated with spontaneous and treatment-induced clearance of HCV infection. Recently, a novel polymorphism was discovered, denoted IFNL4 ΔG > TT (rs368234815, which seems to be a better predictor of spontaneous clearance than the IFNL4 rs12979860 polymorphism. We aimed to determine the prevalence of the IFNL4 ΔG > TT variants and to evaluate the association with spontaneous clearance of HCV infection in Brazilian HIV-1 patients. The IFNL4 ΔG > TT genotypes were analyzed by polymerase chain reaction followed by restriction digestion in 138 HIV-1 positive patients who had an anti-HCV positive result. Spontaneous clearance of HCV was observed in 34 individuals (24.6%. IFNL4 genotype distribution was significantly different between individuals who had spontaneous clearance and chronic HCV patients (p=0.002. The probability of spontaneous clearance of HCV infection for patients with the IFNL4 TT/TT genotype was 3.6 times higher than for patients carrying the IFNL4 ΔG allele (OR=3.63, 95% CI:1.51-8.89, p=0.001. The IFNL4 ΔG > TT polymorphism seems to be better than IFNL4 rs12979860 to predict spontaneous clearance of the HCV in Brazilian HIV-1 positive patients.

Buccal mucosal urethroplasty for balanitis xerotica obliterans related urethral strictures: the outcome of 1 and 2-stage techniques.

Science.gov (United States)

Dubey, Deepak; Sehgal, Anand; Srivastava, Aneesh; Mandhani, Anil; Kapoor, Rakesh; Kumar, Anant

2005-02-01

Balanitis xerotica obliterans (BXO) related strictures are complex and generally managed by 2-staged urethroplasty. We present our results with 1-stage dorsal onlay and 2-stage buccal mucosal urethroplasty for such strictures. Between January 2000 and April 2004, 39 patients underwent buccal mucosal urethroplasty for BXO related anterior urethral strictures. The 25 patients with a salvageable urethral plate (group 1) were treated with 1-stage dorsal onlay urethroplasty using a cosmetic incision. The 14 patients with a severely scarred urethral plate, focally dense segments or active infection (group 2) underwent 2-stage urethroplasty. Outcomes in terms of cosmetic appearance, stricture recurrence and complications in the 2 groups were assessed. At a mean followup of 32.5 months (range 3 to 52) 3 patients (12%) in group 1 had recurrent stricture, of which 2 and 1 were treated with optical urethrotomy and urethral dilation, respectively. All patients had a normal slit-like meatus and none had chordee or erectile dysfunction. Four group 2 patients (28.6%) required stomal revision and 2 had glans cleft narrowing after stage 1 urethroplasty. Following stage 2, 3 patients had recurrent stricture, of whom 2 were treated with optical urethrotomy and 1 underwent repeat urethroplasty. In BXO related strictures with a viable urethral plate 1-stage dorsal onlay buccal mucosal urethroplasty provides excellent intermediate term results. The cosmetic incision described provides a normal, wide caliber, slit-like glans. Two-stage procedures provide satisfactory outcomes but they are associated with a higher revision rate.

A prospective, blinded evaluation of a video-assisted '4-stage approach' during undergraduate student practical skills training.

Science.gov (United States)

Schwerdtfeger, Katrin; Wand, Saskia; Schmid, Oliver; Roessler, Markus; Quintel, Michael; Leissner, Kay B; Russo, Sebastian G

2014-05-22

The 4-stage approach (4-SA) is used as a didactic method for teaching practical skills in international courses on resuscitation and the structured care of trauma patients. The aim of this study was to evaluate objective and subjective learning success of a video-assisted 4-SA in teaching undergraduate medical students. The participants were medical students learning the principles of the acute treatment of trauma patients in their multidiscipline course on emergency and intensive care medicine. The participants were quasi- randomly divided into two groups. The 4-SA was used in both groups. In the control group, all four steps were presented by an instructor. In the study group, the first two steps were presented as a video. At the end of the course a 5-minute objective, structured clinical examination (OSCE) of a simulated trauma patient was conducted. The test results were divided into objective results obtained through a checklist with 9 dichotomous items and the assessment of the global performance rated subjectively by the examiner on a Likert scale from 1 to 6. 313 students were recruited; the results of 256 were suitable for analysis. The OSCE results were excellent in both groups and did not differ significantly (control group: median 9, interquantil range (IQR) 8-9, study group: median 9, IQR 8-9; p = 0.29). The global performance was rated significantly better for the study group (median 1, IQR 1-2 vs. median 2, IQR 1-3; p students in their evaluation after the course, was greater in the study group (85% vs. 80%). It is possible to employ video assistance in the classical 4-SA with comparable objective test results in an OSCE. The global performance was significantly improved with use of video assistance.

Hepatosplenic volumetric assessment at MDCT for staging liver fibrosis

Energy Technology Data Exchange (ETDEWEB)

Pickhardt, Perry J.; Malecki, Kyle; Hunt, Oliver F.; Beaumont, Claire; Kloke, John; Ziemlewicz, Timothy J.; Lubner, Meghan G. [University of Wisconsin School of Medicine and Public Health, Department of Radiology, Madison, WI (United States)

2017-07-15

To investigate hepatosplenic volumetry at MDCT for non-invasive prediction of hepatic fibrosis. Hepatosplenic volume analysis in 624 patients (mean age, 48.8 years; 311 M/313 F) at MDCT was performed using dedicated software and compared against pathological fibrosis stage (F0 = 374; F1 = 48; F2 = 40; F3 = 65; F4 = 97). The liver segmental volume ratio (LSVR) was defined by Couinaud segments I-III over segments IV-VIII. All pre-cirrhotic fibrosis stages (METAVIR F1-F3) were based on liver biopsy within 1 year of MDCT. LSVR and total splenic volumes increased with stage of fibrosis, with mean(±SD) values of: F0: 0.26 ± 0.06 and 215.1 ± 88.5 mm{sup 3}; F1: 0.25 ± 0.08 and 294.8 ± 153.4 mm{sup 3}; F2: 0.331 ± 0.12 and 291.6 ± 197.1 mm{sup 3}; F3: 0.39 ± 0.15 and 509.6 ± 402.6 mm{sup 3}; F4: 0.56 ± 0.30 and 790.7 ± 450.3 mm{sup 3}, respectively. Total hepatic volumes showed poor discrimination (F0: 1674 ± 320 mm{sup 3}; F4: 1631 ± 691 mm{sup 3}). For discriminating advanced fibrosis (≥F3), the ROC AUC values for LSVR, total liver volume, splenic volume and LSVR/spleen combined were 0.863, 0.506, 0.890 and 0.947, respectively. Relative changes in segmental liver volumes and total splenic volume allow for non-invasive staging of hepatic fibrosis, whereas total liver volume is a poor predictor. Unlike liver biopsy or elastography, these CT volumetric biomarkers can be obtained retrospectively on routine scans obtained for other indications. (orig.)

A novel micro/nano 1 × 4 mechanical optical switch

Science.gov (United States)

Lin, Wu-Lang; Fan, Kuang-Chao; Chiang, Li-Hung; Yang, Yao-Joe; Kuo, Wen-Cheng; Chung, Tien-Tung

2006-07-01

This paper presents the design, fabrication and testing of a novel 1 × 4 mechanical optical switch, whose components are fabricated by precision machining and MEMS technologies. The switch uses two relays as the two actuators whose switching direction is perpendicular to each other by an orthogonal arrangement. We adopt a direct fiber-to-fiber principle that aligns the input fiber directly to four output fibers. This configuration eliminates the use of traditional parts such as collimators, turning mirrors or prisms. In addition, due to the use of a fiber holder, the fiber position errors could be reduced to less than 0.27 µm using the two-stage geometry error reduction principle. We have successfully developed a simple and low-cost switch, which performs like most of the 1 × 4 mechanical optical switches that dominate the optics communications market. The advantages of our switch are a small size (20 × 20 × 25 mm3), low cost, high reliability, and the latching function does not need external force for maintaining the state. The experimental results showed that the insertion losses of the four channels are ch1: 0.68 dB, ch2: 1.49 dB, ch3: 0.71 dB and ch4: 0.97 dB. The switching time is 5 ms, the crosstalk <=80 dB. The reliability tests of the insertion loss after 10 000 cycles in four channels yield ch1: 1.67 dB, ch2: 1.63 dB, ch3: 0.75 dB and ch4: 0.98 dB. The size and the cost of our 1 × 4 mechanical optical switch are only about 1/5-1/10 and 1/10 of the series-connect-type and prism-type switches, respectively.

Radiotherapy for stage IV oropharyngeal cancer

International Nuclear Information System (INIS)

Nakamura, Kaori; Akimoto, Tetsuo; Motegi, Atsushi

2008-01-01

Fifty-seven patients with stage IVA-B oropharyngeal cancer treated by definitive radiotherapy in our facility from January 1993 to August 2005 were retrospectively analyzed. The age of the patients was 34-84 (median 62) years old. Thirty-four were male and 14 were female. Subsite of the tumor was anterior: 16, lateral: 39, posterior: 1, and superior: 1. Forty-nine patients were treated with chemotherapy. Induction chemotherapy (ICT) was done in 25 patients, ICT+concurrent chemoradiotherapy (CCRT) in 15 patients, and CCRT in 9 patients. A dose of 60-82 Gy (median 72 Gy) by hyperfractionated radiotherapy, at 1.2 Gy/fraction twice a day, was delivered in 37 patients, and 60-72 Gy (median 66 Gy) with a conventional daily fractionation in 20 patients. Salvage surgery was performed in 5 patients as a part of primary treatment after radiotherapy. The 5-year cause-specific survival rate and disease-free survival rate were 52.9% and 51.4%, respectively. By univariate analysis, the impact of age, sex, T-stage, N-stage, histological differentiation, chemotherapy and fractionation of radiation therapy on survivals were evaluated. T-stage, N-stage and histological differentiation were significantly covariate correlated with survival. The treatment results were not satisfactory. Further investigation of the treatment strategy to improve the treatment outcome of advanced oropharyngeal cancer is desired. (author)

MR staging of pelvic endometriosis. Role of fat-suppression T{sub 1}-weighted images

Energy Technology Data Exchange (ETDEWEB)

Oishi-Tanaka, Yumiko; Itai, Yuji; Anno, Izumi; Matsumoto, Kunihiko; Ebihara, Reiko; Nishida, Masato [Tsukuba Univ., Ibaraki (Japan). Inst. of Clinical Medicine

1996-05-01

We examined whether MR can determine the stage of endometriosis according to the scoring system established and revised by the American Fertility Society (r-AFS), a system which is widely used by gynecologists. We also studied the utility of fat suppression T{sub 1}-weighted images in improving accuracy. Seventeen patients with endometriosis examined by conventional MR were included in this study. All the patients had surgically proved stage III or IV disease. We determined the stage by MR using the following criteria according to the r-AFS system: adnexal masses without normal ovarian tissue were considered deep ovarian lesions, while those with normal tissue were considered superficial. A lack of fat between the lesion and surrounding structures was considered a dense adhesion, and hyperintense spots were considered peritoneal implants. The MR scores of patients with and without fat suppression were correlated with the surgical scores. MR staging corresponded to surgical staging in 15 of the 17 patients. In eight patients, peritoneal implants of less than 1.5 cm were depicted only by fat-suppression images. However, these lesions did not change the score significantly. MR imaging could determine the stage in advanced endometriosis. Fat-suppression could highlight smaller implants. These tiny lesions had little clinical meaning in these advanced cases; however, the clinical value of this technique should be evaluated in milder disease. (author)

Staging laparoscopy improves treatment decision-making for advanced gastric cancer.

Science.gov (United States)

Hu, Yan-Feng; Deng, Zhen-Wei; Liu, Hao; Mou, Ting-Yu; Chen, Tao; Lu, Xin; Wang, Da; Yu, Jiang; Li, Guo-Xin

2016-02-07

To evaluate the clinical value of staging laparoscopy in treatment decision-making for advanced gastric cancer (GC). Clinical data of 582 patients with advanced GC were retrospectively analyzed. All patients underwent staging laparoscopy. The strength of agreement between computed tomography (CT) stage, endoscopic ultrasound (EUS) stage, laparoscopic stage, and final stage were determined by weighted Kappa statistic (Kw). The number of patients with treatment decision-changes was counted. A χ(2) test was used to analyze the correlation between peritoneal metastasis or positive cytology and clinical characteristics. Among the 582 patients, the distributions of pathological T classifications were T2/3 (153, 26.3%), T4a (262, 45.0%), and T4b (167, 28.7%). Treatment plans for 211 (36.3%) patients were changed after staging laparoscopy was performed. Two (10.5%) of 19 patients in M1 regained the opportunity for potential radical resection by staging laparoscopy. Unnecessary laparotomy was avoided in 71 (12.2%) patients. The strength of agreement between preoperative T stage and final T stage was in almost perfect agreement (Kw = 0.838; 95% confidence interval (CI): 0.803-0.872; P advanced GC and decrease unnecessary exploratory laparotomy.

Spectral-domain optical coherence tomography staging and autofluorescence imaging in achromatopsia.

Science.gov (United States)

Greenberg, Jonathan P; Sherman, Jerome; Zweifel, Sandrine A; Chen, Royce W S; Duncker, Tobias; Kohl, Susanne; Baumann, Britta; Wissinger, Bernd; Yannuzzi, Lawrence A; Tsang, Stephen H

2014-04-01

IMPORTANCE Evidence is mounting that achromatopsia is a progressive retinal degeneration, and treatments for this condition are on the horizon. OBJECTIVES To categorize achromatopsia into clinically identifiable stages using spectral-domain optical coherence tomography and to describe fundus autofluorescence imaging in this condition. DESIGN, SETTING, AND PARTICIPANTS A prospective observational study was performed between 2010 and 2012 at the Edward S. Harkness Eye Institute, New York-Presbyterian Hospital. Participants included 17 patients (aged 10-62 years) with full-field electroretinography-confirmed achromatopsia. MAIN OUTCOMES AND MEASURES Spectral-domain optical coherence tomography features and staging system, fundus autofluorescence and near-infrared reflectance features and their correlation to optical coherence tomography, and genetic mutations served as the outcomes and measures. RESULTS Achromatopsia was categorized into 5 stages on spectral-domain optical coherence tomography: stage 1 (2 patients [12%]), intact outer retina; stage 2 (2 patients [12%]), inner segment ellipsoid line disruption; stage 3 (5 patients [29%]), presence of an optically empty space; stage 4 (5 patients [29%]), optically empty space with partial retinal pigment epithelium disruption; and stage 5 (3 patients [18%]), complete retinal pigment epithelium disruption and/or loss of the outer nuclear layer. Stage 1 patients showed isolated hyperreflectivity of the external limiting membrane in the fovea, and the external limiting membrane was hyperreflective above each optically empty space. On near infrared reflectance imaging, the fovea was normal, hyporeflective, or showed both hyporeflective and hyperreflective features. All patients demonstrated autofluorescence abnormalities in the fovea and/or parafovea: 9 participants (53%) had reduced or absent autofluorescence surrounded by increased autofluorescence, 4 individuals (24%) showed only reduced or absent autofluorescence, 3

Immune checkpoint inhibitor PD-1 pathway is down-regulated in synovium at various stages of rheumatoid arthritis disease progression.

LENUS (Irish Health Repository)

Guo, Yanxia

2018-01-01

Immune checkpoint blockade with therapeutic anti-cytotoxic T lymphocyte-associated antigen (CTLA)-4 (Ipilimumab) and anti-programmed death (PD)-1 (Nivolumab and Pembrolizumab) antibodies alone or in combination has shown remarkable efficacy in multiple cancer types, concomitant with immune-related adverse events, including arthralgia and inflammatory arthritis (IA) in some patients. Herein, using Nivolumab (anti-PD-1 antagonist)-responsive genes along with transcriptomics of synovial tissue from multiple stages of rheumatoid arthritis (RA) disease progression, we have interrogated the activity status of PD-1 pathway during RA development. We demonstrate that the expression of PD-1 was increased in early and established RA synovial tissue compared to normal and OA synovium, whereas that of its ligands, programmed death ligand-1 (PD-L1) and PD-L2, was increased at all the stages of RA disease progression, namely arthralgia, IA\\/undifferentiated arthritis, early RA and established RA. Further, we show that RA patients expressed PD-1 on a majority of synovial tissue infiltrating CD4+ and CD8+ T cells. Moreover, enrichment of Nivolumab gene signature was observed in IA and RA, indicating that the PD-1 pathway was downregulated during RA disease progression. Furthermore, serum soluble (s) PD-1 levels were increased in autoantibody positive early RA patients. Interestingly, most of the early RA synovium tissue sections showed negative PD-L1 staining by immunohistochemistry. Therefore, downregulation in PD-1 inhibitory signaling in RA could be attributed to increased serum sPD-1 and decreased synovial tissue PD-L1 levels. Taken together, these data suggest that agonistic PD1 antibody-based therapeutics may show efficacy in RA treatment and interception.

Immune checkpoint inhibitor PD-1 pathway is down-regulated in synovium at various stages of rheumatoid arthritis disease progression.

Science.gov (United States)

Guo, Yanxia; Walsh, Alice M; Canavan, Mary; Wechalekar, Mihir D; Cole, Suzanne; Yin, Xuefeng; Scott, Brittney; Loza, Mathew; Orr, Carl; McGarry, Trudy; Bombardieri, Michele; Humby, Frances; Proudman, Susanna M; Pitzalis, Costantino; Smith, Malcolm D; Friedman, Joshua R; Anderson, Ian; Madakamutil, Loui; Veale, Douglas J; Fearon, Ursula; Nagpal, Sunil

2018-01-01

Immune checkpoint blockade with therapeutic anti-cytotoxic T lymphocyte-associated antigen (CTLA)-4 (Ipilimumab) and anti-programmed death (PD)-1 (Nivolumab and Pembrolizumab) antibodies alone or in combination has shown remarkable efficacy in multiple cancer types, concomitant with immune-related adverse events, including arthralgia and inflammatory arthritis (IA) in some patients. Herein, using Nivolumab (anti-PD-1 antagonist)-responsive genes along with transcriptomics of synovial tissue from multiple stages of rheumatoid arthritis (RA) disease progression, we have interrogated the activity status of PD-1 pathway during RA development. We demonstrate that the expression of PD-1 was increased in early and established RA synovial tissue compared to normal and OA synovium, whereas that of its ligands, programmed death ligand-1 (PD-L1) and PD-L2, was increased at all the stages of RA disease progression, namely arthralgia, IA/undifferentiated arthritis, early RA and established RA. Further, we show that RA patients expressed PD-1 on a majority of synovial tissue infiltrating CD4+ and CD8+ T cells. Moreover, enrichment of Nivolumab gene signature was observed in IA and RA, indicating that the PD-1 pathway was downregulated during RA disease progression. Furthermore, serum soluble (s) PD-1 levels were increased in autoantibody positive early RA patients. Interestingly, most of the early RA synovium tissue sections showed negative PD-L1 staining by immunohistochemistry. Therefore, downregulation in PD-1 inhibitory signaling in RA could be attributed to increased serum sPD-1 and decreased synovial tissue PD-L1 levels. Taken together, these data suggest that agonistic PD1 antibody-based therapeutics may show efficacy in RA treatment and interception.

Delayed entry into HIV care after diagnosis in two specialized care and treatment centres in Cameroon: the influence of CD4 count and WHO staging

Directory of Open Access Journals (Sweden)

Noah F. Takah

2016-07-01

Full Text Available Abstract Background Delayed entry into HIV care has complicated the challenges faced in sub-Saharan Africa due to the high HIV burden. A clear knowledge of the factors affecting delayed entry will be essential in directing interventions towards reducing delayed entry into HIV care. There exist very limited data on delayed entry in Cameroon despite its relevance; hence this study was conducted to determine the rate of delayed entry and its associated factors in HIV programmes in Cameroon. Methods Data used for this study was routine data obtained from the files of HIV patients who were diagnosed between January 1, 2015 and June 30, 2015 at Limbe and Buea regional hospital HIV centers in the South West region of Cameroon. Data analysis was done using SPSS version 20. Results Of the 223 patients included in the study, nearly one-quarter of patients (22.4 % delayed to enter HIV care within 3 months. Those who delayed to enter care were less likely to present at first diagnosis (using HIV rapid test with symptoms such as fever > 1 month (5 % versus 30 %, p = 0.01 and weight loss > 10 % (13 % versus 48 %, p < 0.001. Alcohol consumption, WHO stage and CD4 count levels were also associated with delayed entry in bivariate analysis. In multivariate analysis only CD4 count greater than 500cells/μl and WHO stages I and II were independently associated with delayed entry into HIV care within 3 months. Conclusion In the South West region of Cameroon, approximately 1 out of 4 patients delay to enter HIV care. This high proportion of patients who delay to enter care correlates to the findings recorded by other studies in sub Saharan Africa. Interventions tackling delayed entry into HIV care might need to be favorably directed towards patients that have high CD4 counts and are at very early WHO clinical stages.

Correlation between serum and peritoneal fluid glutathione S-transferases T1 concentration with different stages of endometriosis

Directory of Open Access Journals (Sweden)

Sohail Mashayekhi

2018-03-01

Full Text Available Endometriosis is a gynecological disease defined by the histological presence of endometrial glands and stroma outside the uterine cavity. Ectopic endometrial cell proliferation and chronic inflammation in endometriosis were shown to be associated with oxidative stress (OS induction. OS is a condition in which reactive oxygen species (ROS overproduction and antioxidant deficiency cause a shift in oxidant/antioxidant balance. Glutathione S-transferases (GSTs comprise a family of eukaryotic and prokaryotic phase II metabolic isozymes best known for their ability to catalyze the conjugation of the reduced form of glutathione (GSH to xenobiotic substrates for the purpose of detoxification. The aim of this project was to study the concentrations of GSTT1 in the serum and peritoneal fluid (PF of patients with different stages of endometriosis. Frothy two PF and serum from normal and 152 from different stages of patients with endometriosis (stage I: n = 30, stage II: n = 39, stage III: n = 43 and stage IV: n = 40 were included in this study. The level of GSTT1 in the serum was determined by enzyme linked immunosorbent assay (ELISA. The results showed the presence of GSTT1 in all serum and peritoneal fluid samples, while, starting from stages I to IV endometriosis, a significant decrease in GSTT1 concentration was seen as compared to controls. It is concluded that levels of GSTT1 is negatively correlated with advanced stages of endometriosis. It is also suggested that the detection of serum and/or peritoneal fluid GSTT1 concentration may be valuable in the classifying of endometriosis.

Report on Stage 1 of project CHEMVAL/MIRAGE: verification of speciation models

International Nuclear Information System (INIS)

Read, D.; Broyd, T.W.

1989-01-01

This report describes the results of CHEMVAL Stage 1, an international chemical model verification exercise involving the active participation of 14 organisations within the CEC countries, Sweden, Switzerland and Finland. Five case systems were studied, namely, cement, clay, sandstone, granite and limestone. Overall, good agreement was obtained even for conceptually difficult geochemical simulations. Reasons for divergence in results have been explored and recommendations are made at the appropriate stages for enhancement of the thermodynamic database. A listing of the preliminary CHEMVAL Project Database is provided. (author)

Separate-stage fermentation of biomass to methane

Energy Technology Data Exchange (ETDEWEB)

Clausen, E C; Gaddy, J L

1978-01-01

The production of CH/sub 4/ from orchard grass by anaerobic fermentation was separated into three stages and the kinetics and economics of the process were evaluated. The first stage was acid hydrolysis of the grass polysaccharides, the second stage was acid and alcohol formation from the sugars with a mixed sewage culture, and the third was CH/sub 4/ formation, also with enriched sewage cultures, from the effluent from the second stage reactor. Separating the steps showed a significant increase in CH/sub 4/ production per g of grass, but was less economical than a single-stage process.

Novel 1H-1,2,3-, 2H-1,2,3-, 1H-1,2,4- and 4H-1,2,4-triazole derivatives: a patent review (2008 - 2011).

Science.gov (United States)

Ferreira, Vitor F; da Rocha, David R; da Silva, Fernando C; Ferreira, Patrícia G; Boechat, Núbia A; Magalhães, Jorge L

2013-03-01

The triazoles represent a class of five-membered heterocyclic compounds of great importance for the preparation of new drugs with diverse biological activities because they may present several structural variations with the same numbers of carbon and nitrogen atoms. Due to the success of various triazoles that entered the pharmaceutical market and are still being used in medicines, many companies and research groups have shown interest in developing new methods of synthesis and biological evaluation of potential uses for these compounds. In this review, the authors explored aspects of patents for the 1H-1,2,3-, 2H-1,2,3-, 1H-1,2,4- and 4H-1,2,4-triazole families, including prototypes being considered in clinical studies between 2008 and 2011. The triazoles have been studied for over a century as an important class of heterocyclic compounds and still attract considerable attention due to their broad range of biological activities. More recently, there has been considerable interest in the development of novel triazoles with anti-inflammatory, antiplatelet, antimicrobial, antimycobacterial, antitumoral and antiviral properties and activity against several neglected diseases. This review emphasizes recent perspective and advances in the therapeutically active 1H-1,2,3-, 2H-1,2,3-, 1H-1,2,4- and 4H-1,2,4-triazole derivative patents between 2008 and 2011, covering the development of new chemical entities and new pharmaceuticals. Many studies have focused on these compounds as target structures and evaluated them in several biological targets. The preparation of 1H-1,2,3-, 2H-1,2,3-, 1H-1,2,4- and 4H-1,2,4-triazole derivatives brings to light several issues. There is a need to find new, more efficient preparations for these triazoles that take into consideration current issues in green chemistry, energy saving and sustainability. New diseases are discovered and new viruses and bacteria continue to challenge mankind, so it is imperative to find new prototypes for these

Stage T1-2 prostate cancer with pretreatment PSA 10 ng/ml or less: radiotherapy or surgery?

International Nuclear Information System (INIS)

Keyser, Douglas; Kupelian, Patrick; Zippe, Craig; Klein, Eric

1996-01-01

Purpose: Presently, patients with pretreatment PSA levels ≤10 ng/ml constitute the majority of cases presenting for definitive treatment. Our aim was to determine whether the type of treatment (radiotherapy versus surgery) affected biochemical failure rates in this group of patients. This study is based on 389 patients treated at a single institution. Material and Methods: The charts of all patients treated with either radiotherapy or prostatectomy alone between 1987 and 1993 were reviewed (n=811). Patients with clinical stage T1 or T2 disease, and a pretreatment PSA level (iPSA) of 10.0 or less were analyzed (n=389). Two hundred forty nine (64%) received radical prostatectomy and 140 (36%) received radiotherapy (median dose 66.6 Gy). Pretreatment patient characteristics including clinical stage, biopsy Gleason score (GS) and iPSA level were not significantly different between the radiation and surgery groups (Table 1). The patients treated with radiation were significantly older (median age 70 years vs. 64 years, p<0.05). A total of 37% of the prostatectomy patients had a positive margin. The median follow-up time was 33 months; 1458 follow-up PSA levels were available for analysis. Biochemical failure was defined as a rise in PSA level of 1.0 ng/ml above the nadir PSA level in radiotherapy cases, or any value above 0.2 ng/ml in the prostatectomy cases. Results: The overall 5 year actuarial biochemical relapse free survival (bRFS) rate was 70%. The 5-year bRFS rates for prostatectomy and radiotherapy were identical (70%) (Fig.1). The significant factors affecting bRFS rates were iPSA level (≤4 vs. 4-10 ng/ml) and Gleason score (≤6 vs. ≥7) (Table 2). The 5-year bRFS rates of patients with iPSA ≤4 vs. iPSA 4-10 ng/ml were 92% vs. 61% respectively, p<0.01. The 5-year clinical relapse free survival was 93%. All clinical failures were preceded by biochemical failure. Patients with positive surgical margins did significantly worse than those with negative

Synthesis of 1-Substituted-4-(Pyridin-4-yl)

African Journals Online (AJOL)

Purpose: To synthesize a new series of 1-substituted-4-(pyridin-4-yl) [1,2,4] triazolo [4,3-a]quinazolin- 5(4H)-ones and evaluate them for H1-antihistaminic activity with negligible side effects in guinea pigs. Methods: The synthesized compounds were characterized by Infrared spectroscopy (IR), proton nuclear magnetic ...

Mixed adenosquamous histology is associated with poorer survival of cervical cancer stage 1b

DEFF Research Database (Denmark)

Lauszus, Finn; Tjessem, Ingvild; Al-Far, Hanine M

2016-01-01

Background: Evaluation of histopathological factors for women with radical hysterectomy a.m. Okabayashi for cervical cancer in stage 1bwith similar pre- and postoperative treatment Methods: Data on 141 women with cervical cancer stage 1b were revised. The local patient registry, data charts...... and adenomatous type (pmixed versus pure type). Five year’s survival rate was 40 % (2-78 %) for mixed type and 92 % (87-97 %) for pure type. The mixed type was associated with glandular metastasis (p

Carcinoma of the uterine cervix stage IB and early stage II. Prognostic value of the histological tumor regression after initial brachytherapy

International Nuclear Information System (INIS)

Calais, G.; Le Floch, O.; Chauvet, B.; Reynaud-Bougnoux, A.; Bougnoux, P.

1989-01-01

In our center limited centro pelvic invasive carcinomas of the uterine cervix (less than 4 cm) are treated with brachytherapy and surgery. With these therapeutic modalities no residual carcinoma was observed for 80% of the patients. The purpose of this study was to evaluate our results with this treatment, and to evaluate the prognostic value of the pathological status of the cervix. From 1976 to 1987 we have treated 115 patients with these modalities. Staging system used was the FIGO classification modified for Stage II (divided in early Stage II and late Stage II). Patients were Stage IB (70 cases) and early Stage II (45 cases); 60 Gy were delivered with utero vaginal brachytherapy before any treatment. Six weeks later a radical hysterectomy with pelvic lymphadenectomy was performed. Twenty-one patients with positive nodes received a pelvic radiotherapy (45 to 55 Gy). Local control rate was 97% (100% for Stage IB and 93% for early Stage II). Uncorrected 10-year actuarial survival rate was 96% for Stage IB and 80% for early Stage II patients. No treatment failure was observed for Stage IB patients. Ninety-two patients (80%) had no residual carcinoma in the cervix (group 1) and 23 patients (20%) had a residual tumor (group 2). The sterilization rate of the cervix was 87% for Stage IB tumors versus 69% for early Stage II, and was 82% for N- patients versus 68% for N+ patients. Ten year actuarial survival rate was 92% for group 1 and 78% for group 2 (p = 0, 1). Grade 3 complications rate was 6%. We conclude that brachytherapy + surgery is a safe treatment for limited centro pelvic carcinomas of the uterine cervix (especially Stage IB) and that pathological status of the cervix after brachytherapy is not a prognostic factor

Key Markers of mTORC1-Dependent and mTORC1-Independent Signaling Pathways Regulating Protein Synthesis in Rat Soleus Muscle During Early Stages of Hindlimb Unloading.

Science.gov (United States)

Mirzoev, Timur; Tyganov, Sergey; Vilchinskaya, Natalia; Lomonosova, Yulia; Shenkman, Boris

2016-01-01

The purpose of the study was to assess the amount of rRNA and phosphorylation status of the key markers of mTORC1-dependent (70s6k, 4E-BP1) and mTORC1-independent (GSK-3β, AMPK) signaling pathways controlling protein synthesis in rat soleus during early stages of mechanical unloading (hindlimb suspension (HS) for 1-, 3- and 7 days). The content of the key signaling molecules of various anabolic signaling pathways was determined by Western-blotting. The amount of 28S rRNA was evaluated by RT-PCR. The rate of protein synthesis was assessed using in-vivo SUnSET technique. HS for 3 and 7 days induced a significant (pprotein synthesis in soleus muscle in comparison with control. HS within 24 hours resulted in a significant (pprotein synthesis in rat soleus during early stages of simulated microgravity is associated with impaired ribosome biogenesis as well as reduced activity of mTORC1-independent signaling pathways. © 2016 The Author(s) Published by S. Karger AG, Basel.

Prospective Multi-Institutional Study of Definitive Radiotherapy With High-Dose-Rate Intracavitary Brachytherapy in Patients With Nonbulky (<4-cm) Stage I and II Uterine Cervical Cancer (JAROG0401/JROSG04-2)

Energy Technology Data Exchange (ETDEWEB)

Toita, Takafumi, E-mail: b983255@med.u-ryukyu.ac.jp [Department of Radiology, Graduate School of Medical Science, University of Ryukyus, Okinawa (Japan); Kato, Shingo [Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Niibe, Yuzuru [Department of Radiology, School of Medicine, Kitasato University, Sagamihara (Japan); Ohno, Tatsuya [Gunma University Heavy Ion Medical Center, Maebashi (Japan); Kazumoto, Tomoko [Department of Radiology, Saitama Cancer Center, Saitama (Japan); Kodaira, Takeshi [Department of Radiation Oncology, Aichi Cancer Center, Nagoya (Japan); Kataoka, Masaaki [Department of Radiology, National Shikoku Cancer Center, Ehime (Japan); Shikama, Naoto [Department of Radiation Oncology, Saku Central Hospital, Saku (Japan); Kenjo, Masahiro [Department of Radiation Oncology, Graduate School of Medical Science, Hiroshima University, Hiroshima (Japan); Tokumaru, Sunao [Department of Radiology, Saga University, Saga (Japan); Yamauchi, Chikako [Department of Radiation Oncology, Shiga Medical Center for Adults, Moriyama (Japan); Suzuki, Osamu [Department of Radiation Oncology, Osaka Medical Center for Cancer, Osaka (Japan); Sakurai, Hideyuki [Proton Medical Research Center and Tsukuba University, Tsukuba (Japan); Numasaki, Hodaka; Teshima, Teruki [Department of Medical Physics and Engineering, Graduate School of Medicine, Osaka University, Suita, Osaka (Japan); Oguchi, Masahiko [Department of Radiation Oncology, Cancer Institute Hospital, Tokyo (Japan); Kagami, Yoshikazu [Radiation Oncology Division, National Cancer Center Hospital, Tokyo (Japan); Nakano, Takashi [Department of Radiation Oncology, Gunma University, Graduate School of Medicine, Maebashi (Japan); Hiraoka, Masahiro [Department of Radiation Oncology and Image-applied Therapy, Kyoto University, Graduate School of Medicine, Kyoto (Japan); Mitsuhashi, Norio [Department of Radiation Oncology, Tokyo Women' s Medical University, Tokyo (Japan)

2012-01-01

Purpose: To determine the efficacy of a definitive radiotherapy protocol using high-dose-rate intracavitary brachytherapy (HDR-ICBT) with a low cumulative dose schedule in nonbulky early-stage cervical cancer patients, we conducted a prospective multi-institutional study. Methods and Materials: Eligible patients had squamous cell carcinoma of the intact uterine cervix, Federation of Gynecologic Oncology and Obstetrics (FIGO) stages Ib1, IIa, and IIb, tumor size <40 mm in diameter (assessed by T2-weighted magnetic resonance imaging), and no pelvic/para-aortic lymphadenopathy. The treatment protocol consisted of whole-pelvis external beam radiotherapy (EBRT) of 20 Gy/10 fractions, pelvic EBRT with midline block of 30 Gy/15 fractions, and HDR-ICBT of 24 Gy/4 fractions (at point A). The cumulative biologically effective dose (BED) was 62 Gy{sub 10} ({alpha}/{beta} = 10) at point A. The primary endpoint was the 2-year pelvic disease progression-free (PDPF) rate. All patients received a radiotherapy quality assurance review. Results: Between September 2004 and July 2007, 60 eligible patients were enrolled. Thirty-six patients were assessed with FIGO stage Ib1; 12 patients with stage IIa; and 12 patients with stage IIb. Median tumor diameter was 28 mm (range, 6-39 mm). Median overall treatment time was 43 days. Median follow-up was 49 months (range, 7-72 months). Seven patients developed recurrences: 3 patients had pelvic recurrences (2 central, 1 nodal), and 4 patients had distant metastases. The 2-year PDPF was 96% (95% confidence interval [CI], 92%-100%). The 2-year disease-free and overall survival rates were 90% (95% CI, 82%-98%) and 95% (95% CI, 89%-100%), respectively. The 2-year late complication rates (according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer of Grade {>=}1) were 18% (95% CI, 8%-28%) for large intestine/rectum, 4% (95% CI, 0%-8%) for small intestine, and 0% for bladder. No Grade {>=}3 cases were

Hydrobiological study of the small stream on the Czech–Moravian Highlands

Directory of Open Access Journals (Sweden)

Ivo Sukop

2010-01-01

Full Text Available Zoobenthos of the Fryšávka Rivulet was investigated in the years 2007–2008. Research included also physico-chemical factors of water (temperature, pH, conductivity, oxygen saturation. Altogether, 144 taxa of zoobenthos were determined in the Fryšávka Rivulet: Coelenterata (1 taxon, Turbellaria (1 taxon, Oligochaeta (6 taxa, Hirudinea (1 taxon, Mollusca (5 taxa, Amphipoda (1 taxon, Decapoda (1 taxon, Acari (1 taxon, Ephemeroptera (18 taxa, Plecoptera (18 taxa, Heteroptera (1 taxon, Megaloptera (1 taxon, Planipennia (1 taxon, Trichoptera (36 taxa, Coleoptera (8 taxa, Diptera (44 taxa. Altogether, 76 taxa of zoobenthos were determined in Medlovka brook: Coelenterata (1 taxon, Turbellaria (1 taxon, Oligochaeta (2 taxa, Mollusca (1 taxon, Isopoda (1 taxon, Amphipoda (1 taxon, Acari (1 taxon, Ephemeroptera (14 taxa, Plecoptera (8 taxa, Megaloptera (1 taxon, Trichoptera (17 taxa, Coleoptera (6 taxa, Diptera (22 taxa.The average abundance of zoobenthos of the Fryšávka Rivulet was 3208 ind.m−2, the average biomass was 7.5 g . m−2, respectively. The same values for the Medlovka brook were: abundance 3238 ind.m−2 and biomass 5.8 g . m−2. The average value of the saprobic index for the whole Fryšávka Rivulet was 1.25 (oligosaprobity, for the Medlovka brook 1.42 (oligosaprobity.

FDG-PET in the initial staging of squamous cell oesophageal carcinoma

International Nuclear Information System (INIS)

Buchmann, I.; Schreckenberger, M.; Bartenstein, P.; Hansen, T.; Brochhausen, C.; Kneist, W.; Junginger, T.; Oberholzer, K.

2006-01-01

Squamous cell oesophageal carcinoma is the most common carcinoma of the oesophagus worldwide. The tumour stage as most important prognostic factor determines the clinical management. Aim of this study was to evaluate the value of FDG-PET 1. in imaging the primary tumour and 2. in N- and M-staging of squamous cell oesophogeal carcinoma. Patients, methods: in 20 patients with histological proven squamous cell carcinoma of the upper and middle oesophagus, FDG-PET was performed in standard technique prior to therapy. FDG uptake in the primary was determined by calculation of the SUVmax. NM-staging due to PET findings was performed as designated by the AJCC/UICC group classification and was compared with pathological and clinically based staging. Sensitivities, specificities and accuracies were calculated. Results: in 19 of 20 patients, primary squamous cell oesopohageal carcinoma was detected by FDG-PET findings with a maximum SUV of 12.5 (mean) ± 5.1 (median 11.5; range 4.8-23.8). One carcinoma in situ was missed. The sensitivity of FDG-PET in imaging the primary tumour was 96%. The sensitivities, specificities and accuracies were 20%, 100%, 58% for N-staging, and 60%, 86% and 93% for M-staging. PET findings caused changes of therapy in 5% (1 patient). Conclusions: FDG-PET was excellent in imaging the primary of squamous cell oesophageal carcinoma in stage T1-T4 and was efficient in M-staging. The low sensitivity in N-staging is of inferior clinical importance. The efficacy of FDG-PET seems to be not significantly be influenced by the histological subtype of oesophageal carcinoma. (orig.)

Factors influencing subject selection in upper secondary education (Key Stage 4 for males and females in England

Directory of Open Access Journals (Sweden)

Joanne Vaughan

2015-08-01

Full Text Available Background Research to date has investigated the potential factors that influence students’ decisions in opting to study certain subjects during their upper secondary education. Trends in subject selection at this level (Key Stage 4 have been maintained over time and have consistently displayed comparable differences for males and females. It is recognised that males typically opt for subjects such as physical education and science, while females are traditionally noted as favouring the arts and humanities. These educational decisions may impact on future occupational directions. In light of recent initiatives, such as the English Baccalaureate, it is of interest to explore whether such measures have had an influence on this noted gender gap. Participants and procedure The present study investigates the potential predictors of subject selection, while controlling for gender, offering a specific focus on the education system in England. Attention is given to students’ perceived academic ability and attitude toward school, and how such factors may guide subject choice. Participants (N = 276 were students currently in the process of selecting optional modules for Key Stage 4 study. Results The findings demonstrate that female students are less likely than their male counterparts to opt for physical education (PE and business studies/information and communication technology (ICT as preferred modules, in comparison to ‘creative and performance’ subjects (reference category. Higher levels of reported masculinity were also shown to relate to the up-take of PE at Key Stage 4. Conclusions The implications of these findings are discussed in relation to existing research and practical contributions to the educational arena.

Concepts to meet non-road stage IV / Tier 4 emission legislation; Konzepte fuer die Emissionsgesetzgebung. Non-Road Stage IV / Tier 4

Energy Technology Data Exchange (ETDEWEB)

Cartus, T.; Herrmuth, H.; Stein, G. [AVL List GmbH, Graz (Austria); Scherm, P. [Euromot - European Association of Internal Combustion Engine Mfrs., Frankfurt am Main (Germany)

2007-12-15

By December 2007, the EC will have to submit a new proposal for Stage IV emissions limits for Non-Road Mobile Machinery. Industry is committed to contributing to this process and has asked AVL to carry out a study as a neutral engineering company. The main topics of this study are described in this article. (orig.)

Cytotoxicity and Pro-Apoptotic Activity of 2,2´-Bis[4,5-bis(4-hydroxybenzyl-2-(4-hydroxyphenylcyclopent-4-en-1,3-dione], a Phenolic Cyclopentenedione Isolated from the Cyanobacterium Strain Nostoc sp. str. Lukešová 27/97

Directory of Open Access Journals (Sweden)

Jan Vacek

2011-05-01

Full Text Available The cytotoxicity of the polyphenol 2,2´-bis[4,5-bis(4-hydroxybenzyl-2-(4-hydroxyphenylcyclopent-4-en-1,3-dione], nostotrebin 6 (NOS-6, was tested under in vitro conditions using mouse fibroblasts (BALB/c cells. Identification of NOS-6 and its uptake into fibroblasts was examined by multi-stage mass spectrometry analysis with the following fragmentation pattern: MS (m/z [M+H]+ 799.1 → MS2 399.1 → MS3 305.1 → MS4 277.1. Using several cell viability assays, the IC50 of NOS-6 after 24 h incubation was found to be 8.48 ± 0.16/12.15 ± 1.96 µM (neutral red/MTT assay which was higher than that of doxorubicin. It was found that NOS-6 is capable of inducing both types of cell death, apoptosis and necrosis in a dose-dependent manner. The biological activities of the cyclopentenediones and preliminary data on NOS-6 cytotoxicity are discussed.

A case of urinary retention in the early stages of herpes simplex virus type-1 encephalitis.

Science.gov (United States)

Fukuoka, Takuya; Nakazato, Yoshihiko; Miyake, Akifumi; Tamura, Naotoshi; Araki, Nobuo; Yamamoto, Toshimasa

2017-06-01

A 70-year-old man developed urinary retention in the early stages of herpes simplex virus (HSV) type-1 encephalitis. A nerve conduction study suggested latent myeloradiculitis. This is the first report of human herpes simplex virus-1 encephalitis followed by urinary retention at early stage from the onset like the Elsberg syndrome. Although relatively few similar cases have been reported, we consider that urinary retention is common in HSV-1 encephalitis, in which disturbances of consciousness usually require bladder catheterization from the onset. We further emphasize that urinary retention may occasionally occur in early stages of HSV-1 encephalitis, with a significant possibility of recovery. Copyright © 2017. Published by Elsevier B.V.

Health-related quality of life across all stages of autosomal dominant polycystic kidney disease.

Science.gov (United States)

Eriksson, Daniel; Karlsson, Linda; Eklund, Oskar; Dieperink, Hans; Honkanen, Eero; Melin, Jan; Selvig, Kristian; Lundberg, Johan

2017-12-01

A limited number of studies have assessed health-related quality of life (HRQoL) in autosomal dominant polycystic kidney disease (ADPKD). Results to date have been conflicting and studies have generally focused on patients with later stages of the disease. This study aimed to assess HRQoL in ADPKD across all stages of the disease, from patients with early chronic kidney disease (CKD) to patients with end-stage renal disease. A study involving cross-sectional patient-reported outcomes and retrospective clinical data was undertaken April-December 2014 in Denmark, Finland, Norway and Sweden. Patients were enrolled into four mutually exclusive stages of the disease: CKD stages 1-3; CKD stages 4-5; transplant recipients; and dialysis patients. Overall HRQoL was generally highest in patients with CKD stages 1-3, followed by transplant recipients, patients with CKD stages 4-5 and patients on dialysis. Progressive disease predominately had an impact on physical health, whereas mental health showed less variation between stages of the disease. A substantial loss in quality of life was observed as patients progressed to CKD stages 4-5. Later stages of ADPKD are associated with reduced physical health. The value of early treatment interventions that can delay progression of the disease should be considered. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA.

Radiation therapy for early stage (T1 - T2) sarcomatoid carcinoma of true vocal cords: outcomes and patterns of failure

International Nuclear Information System (INIS)

Ballo, Matthew T.; Garden, Adam S.; El-Naggar, Adel K.; Morrison, William H.; Ang, K. Kian

1997-01-01

Objectives/hypothesis: Sarcomatoid carcinoma of head and neck mucosal sites is a rare malignancy surrounded with much controversy. One factor consistently reported yet not well supported throughout the literature is their relative radioresistance and a general belief that surgery is the treatment of choice. Our objective was to determine if patients treated with radiation for early glottic carcinoma with this histologic diagnosis had worse outcomes than typical squamous cell carcinoma of similar stage. Materials and Methods: Twenty-eight cases of early stage sarcomatoid carcinoma of the larynx treated with definitive doses of megavoltage irradiation between 1969 and 1995 at the University of Texas M.D. Anderson Cancer Center form the cohort for this analysis. All pathologic material was reviewed to confirm the diagnosis. Follow-up ranged from 1.5 - 24 years (median, 10 years). Results: Twenty-one patients were staged T1 and 7 patients had stage T2 disease. Sixteen tumors had the more typical polypoid morphology of sarcomatoid carcinoma. All patients were treated with small laryngeal fields, median size 20 cm2, and to a median dose of 65 Gy. Four patients (14%) had local disease recurrence. All 4 patients had salvage total laryngectomies and remained free of local disease. Only one patient manifested regional and distant disease. The 10-year actuarial survival rate was 63%. Conclusions: Patients with early staged sarcomatoid carcinoma of the glottis treated with radiation had similar control rates to irradiated patients with similar volume disease with the more typical squamous cell carcinoma. We do not believe that the histologic diagnosis of sarcomatoid carcinoma by itself should influence the decision to not treat a patient with early staged glottic disease with irradiation

Fragrance material review on 1-(2,4,4,5,5-pentamethyl-1-cyclopenten-1-yl)ethan-1-one.

Science.gov (United States)

Scognamiglio, J; Letizia, C S; Api, A M

2013-12-01

A toxicologic and dermatologic review of 1-(2,4,4,5,5-pentamethyl-1-cyclopenten-1-yl)ethan-1-one when used as a fragrance ingredient is presented. 1-(2,4,4,5,5-Pentamethyl-1-cyclopenten-1-yl)ethan-1-one is a member of the fragrance structural group Alkyl Cyclic Ketones. These fragrances can be described as being composed of an alkyl, R1, and various substituted and bicyclic saturated or unsaturated cyclic hydrocarbons, R2, in which one of the rings may include up to 12 carbons. Alternatively, R2 may be a carbon bridge of C2-C4 carbon chain length between the ketone and cyclic hydrocarbon. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for 1-(2,4,4,5,5-pentamethyl-1-cyclopenten-1-yl)ethan-1-one were evaluated then summarized and includes physical properties, acute toxicity, skin irritation, mucous membrane (eye) irritation, skin sensitization, phototoxicity, and photoallergy data. A safety assessment of the entire Alkyl Cyclic Ketones will be published simultaneously with this document; please refer to Belsito et al. (Belsito, D., Bickers, D., Bruze, M., Calow, P., Dagli, M., Fryer, A.D., Greim, H., Miyachi, Y., Saurat, J.H., Sipes, I.G., 2013. A Toxicologic and Dermatologic Assessment of Alkyl Cyclic Ketones When Used as Fragrance Ingredients (submitted for publication)) for an overall assessment of the safe use of this material and all Alkyl Cyclic Ketones in fragrances. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effectiveness of fenbendazole against later 4th-stage Strongylus vulgaris in ponies.

Science.gov (United States)

Slocombe, J O; McCraw, B M; Pennock, P W; Baird, J D

1983-12-01

Twelve pony foals (reared worm-free) were inoculated with Strongylus vulgaris. Approximately 8 weeks later, 4 of the foals were given fenbendazole (10% suspension) at a dosage rate of 10 mg/kg of body weight daily for 5 days and 4 foals were given the suspension at a dosage rate of 50 mg/kg daily for 3 days; the remaining foals were given a placebo. All treatments were administered by stomach tube. Fenbendazole was 99.6 and 97.9% effective in the 2 treatment groups, respectively, in eliminating later 4th-stage S vulgaris larvae located near the origin of major intestinal arteries. On microscopic examination of the ileocolic artery from fenbendazole-treated foals, a few larval remnants were found beneath the tunica intima in small organized mural thrombi overgrown with endothelium. It would appear that larvae are rapidly destroyed after administration of fenbendazole. A pony foal reared on pasture and with arteriographic evidence of arteritis of the cranial mesenteric and ileocolic arteries was treated with fenbendazole (10% suspension) by stomach tube at a dosage rate of 50 mg/kg of body weight daily for 3 days. By arteriographic examination made 4 weeks later, there was evidence of regression of the lesion, and at necropsy done a week later, there was no arteritis or larvae in the lumen of those arteries.

Evidence of two-stage melting of Wigner solids

Science.gov (United States)

Knighton, Talbot; Wu, Zhe; Huang, Jian; Serafin, Alessandro; Xia, J. S.; Pfeiffer, L. N.; West, K. W.

2018-02-01

Ultralow carrier concentrations of two-dimensional holes down to p =1 ×109cm-2 are realized. Remarkable insulating states are found below a critical density of pc=4 ×109cm-2 or rs≈40 . Sensitive dc V-I measurement as a function of temperature and electric field reveals a two-stage phase transition supporting the melting of a Wigner solid as a two-stage first-order transition.

Comparison of single-stage and temperature-phased two-stage anaerobic digestion of oily food waste

International Nuclear Information System (INIS)

Wu, Li-Jie; Kobayashi, Takuro; Li, Yu-You; Xu, Kai-Qin

2015-01-01

Highlights: • A single-stage and two two-stage anaerobic systems were synchronously operated. • Similar methane production 0.44 L/g VS_a_d_d_e_d from oily food waste was achieved. • The first stage of the two-stage process became inefficient due to serious pH drop. • Recycle favored the hythan production in the two-stage digestion. • The conversion of unsaturated fatty acids was enhanced by recycle introduction. - Abstract: Anaerobic digestion is an effective technology to recover energy from oily food waste. A single-stage system and temperature-phased two-stage systems with and without recycle for anaerobic digestion of oily food waste were constructed to compare the operation performances. The synchronous operation indicated the similar ability to produce methane in the three systems, with a methane yield of 0.44 L/g VS_a_d_d_e_d. The pH drop to less than 4.0 in the first stage of two-stage system without recycle resulted in poor hydrolysis, and methane or hydrogen was not produced in this stage. Alkalinity supplement from the second stage of two-stage system with recycle improved pH in the first stage to 5.4. Consequently, 35.3% of the particulate COD in the influent was reduced in the first stage of two-stage system with recycle according to a COD mass balance, and hydrogen was produced with a percentage of 31.7%, accordingly. Similar solids and organic matter were removed in the single-stage system and two-stage system without recycle. More lipid degradation and the conversion of long-chain fatty acids were achieved in the single-stage system. Recycling was proved to be effective in promoting the conversion of unsaturated long-chain fatty acids into saturated fatty acids in the two-stage system.

Tripoli-4.4 Jeff-3.1 based libraries; Les bibliotheques Jeff-3.1 pour Tripoli-4.4

Energy Technology Data Exchange (ETDEWEB)

Jouanne, C. [CEA Saclay Dept. Modelisation de Systemes et Structures, 91 - Gif sur Yvette (France); Sublet, J.Ch. [CEA Cadarache, Dept. d' Etudes des Reacteurs, 13 - Saint Paul lez Durance (France)

2006-07-01

Continuous-energy and multi-temperatures TRIPOLI-4.4 libraries, derived from the Joint European Fusion-Fission JEFF-3.1 evaluations, have been generated using the NJOY-99.112 processing code system. They include the continuous-energy neutron JEFF-3.1/General Purpose and thermal S({alpha},{beta}) JEFF-3.1/Thermal libraries and data tables. The processing steps and features are explained together with the Quality Assurance processes and records linked to the generation of such multipurpose libraries. (authors)

Postoperative high dose rate vaginal apex brachytherapy in stage I endometrial adenocarcinoma

International Nuclear Information System (INIS)

Turner, B.; Knisely, J.; Kacinski, B.; Roberts, K.; Peschel, R.; Gumbs, A.; Rutherford, T.; Edraki, B.; Schwartz, P.; Chambers, J.; Kohorn, E.; Wilson, L.

1996-01-01

Introduction: Patients with stage I endometrial adenocarcinoma have traditionally been treated with TAH/BSO and radiation. The reported incidence of local recurrence in surgically treated patients with Figo stage IA or IB endometrial adenocarcinoma is 4-10% at 2 years. Combined surgery and radiation has resulted in a reduction of recurrence to 2-6%. We report the presentation, local and distant control, salvage rate, survival and complications for patients undergoing high dose rate (HDR) vaginal apex brachytherapy following surgery. Methods: Between 1985 and 1994 a total of 302 patients with Figo stage I endometrial carcinoma were treated with HDR Ir-192 vaginal apex brachytherapy to a total dose of 21 Gy in 3 fractions at 0.5 cm from the vaginal mucosa. The pathologic stage by treatment group was IA: 31%, IB: 68%, and IC: 1%. The histologic grade of the patient's tumors was grade 1: 69%, 2: 27%, and 3: 4%. The median time from surgery to radiation was 33 days (range 14-66 days). The median follow-up for 300 patients with stage IA (91 patients), IB (205 patients), and IC (4 patients) was respectively 36, 34 and 40 months (2 patients lost to follow-up prior to 6 months). Results: Patients presented with vaginal bleeding (94%) or abnormal pap smear (6%) at a median age for stage IA and IB, of 55 and 64 years, respectively. The crude overall survival of the patient population at 2 years is 95%. Median overall time to failure is 19.5 months (range 10-36 months). The overall failure rate was 2.7% (8 patients), local failure only 1.0% (38% of failed group), distant failure only 0.3% (12% of failed group) and combined local/distant failure 1.3% (50% of failed group). The local failure rate for pathologic stage IA patients was 1.0% and no distant disease was observed. The local failure rate for pathologic stage IB patients was 3.4% 7/205 and distant failure was 2.4% 5/205. The majority of patients with recurrence had grade 2 histologic changes 5/8. The overall salvage rate

4-Aminobenzoic acid–1,2-bis(4-pyridylethane (2/1

Directory of Open Access Journals (Sweden)

Fwu Ming Shen

2010-07-01

Full Text Available In the title compound, C12H12N2·2C7H7NO2, the 4-aminobenzoic acid molecules are linked by O—H...N hydrogen bonds to 1,2-bis(4-pyridylethane, forming linear hydrogen bonded chains parallel to [2overline{1}1]. The structure exhibits a hydrogen-bonding network involving COOH...N(pyridyl and amine and carboxylic N—H... O interactions. In addition, π–π stacking interactions [centroid–centroid distance = 3.8622 (14 Å] are also present.

Trichloro(1,4,7-trimethyl-1,4,7-triazacyclononane)chromium(III)

DEFF Research Database (Denmark)

Klitgaard, Søren Kegnaes; Schau-Magnussen, Magnus

2005-01-01

The 1,4,7-trimethyl-1,4,7-triazacyclononane (tmtacn) ligand has become one of the classic ligands in coordination chemistry (Wieghardt et al., 1982 [Wieghardt, K., Chaudhuri, P., Nuber, B. & Weiss, J. (1982). Inorg. Chem. 21, 3086-3090.] ). In recent years, tmtacn-metal complexes ...

Staging properties of potassium-ammonia ternary graphite intercalation compounds at high ammonia pressure

Science.gov (United States)

Qian, X. W.; Solin, S. A.

1989-04-01

The pressure dependence of the (00l) x-ray diffraction patterns of the ternary graphite intercalation compound K(NH3)xC24 has been studied in the range 0.5-11 kbar (for which x~4.5) using a diamond anvil cell. A special apparatus for loading the cell with liquid ammonia at room temperature has been constructed and is briefly described. In these experiments, the pressure-transmitting fluid was also an intercalant, namely ammonia. Therefore, the chemical potential of this species was linearly coupled to the applied pressure in contrast to the usual case where the pressure-transmitting fluid is chemically passive. The pressure dependences of the basal spacings and of the relative intensities of key reflections have been measured, as have the compressibilities of the stage-1 and stage-2 components of the two-phase system. Basal-spacing anomalies and anomalies in the relative intensities occur at pressures of ~3.5 and 8.0 kbar and are tentatively attributed to in-plane coordination changes in the potassium-ammonia ratio. Using thermodynamic arguments and Le Chatelier's principle we show quantitatively that a staging phase transition from pure stage-1 phase to an admixture of stage-1 and stage-2 is expected with increased pressure above 10 bar in agreement with experiment. The saturation ammonia compositions (x values) of the admixed stages are found to be 4.5 and 5.4 for the stage-1 and -2 components, respectively. This result is interpreted as evidence that the composition is not sterically limited but is determined by the binding energy of ammonia for potassium and by the perturbation to this energy from the guest-host interaction.

[Hydrogen bis(1,2,4-triazole] 1,2,4-triazolium bis(3-carboxy-4-hydroxybenzenesulfonate 1,2,4-triazole disolvate

Directory of Open Access Journals (Sweden)

Ming-qiang Qiu

2010-08-01

Full Text Available The title compound, C2H4N3+·[H(C2H3N32]+·2C7H5O6S−·2C2H3N3, consists of two types of 1,2,4-triazole monocation, one protonated at the 2-site lying across a twofold axis and the other protonated at the 4-site with the H atom disordered over a center of symmetry, a 5-sulfosalicylate anion and a neutral 1,2,4-triazole molecule. The component ions are linked into a three-dimensional network by a combination of N—H...O, N—H...N, O—H...O, O—H...N, C—H...O and C—H...N hydrogen bonds. In addition, benzene–benzene π–π interactions of 3.942 (2 Å [interplanar spacing = 3.390 (2 Å] and C—O...π (3.331 Å interactions are observed.

Genetic modification of risk assessment based on staging of preclinical type 1 diabetes in siblings of affected children.

Science.gov (United States)

Mrena, S; Savola, K; Kulmala, P; Reijonen, H; Ilonen, J; Akerblom, H K; Knip, M

2003-06-01

We set out to study the association between human leukocyte antigen-defined genetic disease susceptibility and the stage of preclinical type 1 diabetes and whether genetic predisposition affects the natural course of preclinical diabetes in initially nondiabetic siblings of affected children. A total of 701 initially unaffected siblings were graded into four stages of preclinical type 1 diabetes based on the initial number of disease-associated autoantibodies detectable close to the time of diagnosis of the index case: no prediabetes (no antibodies), early (one antibody specificity), advanced (two antibodies), and late prediabetes (three or more antibodies). Another classification system covering 659 siblings was based on a combination of the initial number of antibodies and the first-phase insulin response (FPIR) to iv glucose: no prediabetes (no antibodies), early (one antibody specificity, normal FPIR), advanced (two or more antibodies, normal FPIR), and late prediabetes (at least one antibody, reduced FPIR). Genetic susceptibility to type 1 diabetes was defined by human leukocyte antigen identity and DR and DQ genotypes. There was a higher proportion of siblings with late prediabetes initially among those with strong genetic disease susceptibility than among those with decreased genetic predisposition (16.7% vs. 0.5%; P siblings with no signs of prediabetes among those with genotypes conferring decreased risk (91.2% vs. 70.4% among those with high-risk DQB1 genotypes; P siblings than when combined with genetic susceptibility. Genetic susceptibility played a role in whether the initial prediabetic stage progressed (progression in 29.6% of the high-risk siblings compared with 6.6% of the siblings with DQB1 genotypes conferring decreased risk; P siblings of affected children.

Appendectomy in the surgical staging of ovarian carcinoma.

Science.gov (United States)

Beşe, T; Kösebay, D; Kaleli, S; Oz, A U; Demirkiran, F; Gezer, A

1996-06-01

Extensive debulking is accepted as the primary method of operative management for carcinoma of the ovary. However, there is no consensus regarding the role of appendectomy in primary surgical treatment. The aim of this study was to assess the role of appendectomy in the surgical staging and cytoreduction of ovarian carcinoma. The study was a retrospective review of 90 primary malignant ovarian carcinoma patients who had an appendectomy in addition to primary cytoreductive surgery. Out of 90 patients, 10 (11.1%) had metastasis to the appendix. The rate of metastasis to the appendix was 11.5% (9/78) in malignant epithelial ovarian carcinomas and 8.3% (1/12) in non-epithelial ovarian tumors. Of the patients with metastasis in the appendix, malignant epithelial ovarian tumors were identified in 90% (serous: 70%; clear cell: 20%), and non-epithelial malignant ovarian tumor were disclosed in 10% (granulosa cell carcinoma). There were no metastases to the appendix in the other histological types. Although metastasis to the appendix was not observed in early stage ovarian carcinomas, it was detected in 21.4% (9/42) of stage III and 50% (1/2) of stage IV. Macroscopic tumor metastasis in the abdomen was noted in all patients with metastasis to the appendix. Appendectomy for stage I and II patients was not beneficial and did not affect final staging. As a result, for the proper staging of ovarian carcinoma there is no advantage to the addition of routine appendectomy to primary cytoreductive surgery in early stage (stage I and II) malignant epithelial ovarian tumors. Appendectomy would contribute to the cytoreduction of advanced stage disease if it is macroscopically involved.

Poly[[[[1-ethyl-6,8-difluoro-7-(3-methylpiperazin-1-yl-4-oxo-1,4-dihydroquinoline-3-carboxylato]cadmium]-μ-benzene-1,4-dicarboxylato] trihydrate

Directory of Open Access Journals (Sweden)

Xin-Ping Kang

2010-11-01

Full Text Available In the title layered coordination polymer, {[Cd(C17H18F2N3O3(C8H4O4]·3H2O}n, the CdII atom exhibits a very distorted CdO6 octahedral geometry defined by one O3,O4-bidentate 1-ethyl-6,8-difluoro-7-(3-methylpiperazin-1-yl-4-oxo-1,4-dihydroquinoline-3-carboxylate (lome ligand, one O,O′-bidentate benzene-1,4-dicarboxylate (bdc dianion and two O-monodentate bdc dianions. Both the bdc species in the asymmetric unit are completed by crystallographic inversion symmetry. The bridging bdc dianions link the cadmium nodes into a rectangular grid lying parallel to (01overline{1}. A network of N—H...O and O—H...O hydrogen bonds helps to establish the packing.

Structure determination of two structural analogs, named 3-[1-(2-fluoro-4-biphenyl)ethyl]-6-(4-fluorophenyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (C23H16F2N4S) and 3-[1-(2-fluoro-4-biphenyl)ethyl]-6-(4-chlorophenyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (C23H16ClFN4S) by synchrotron X-ray powder diffraction

Energy Technology Data Exchange (ETDEWEB)

Gündoğdu, Gülsüm; Aytaç, Sevim Peri; Müller, Melanie; Tozkoparan, Birsen; Kaynak, Filiz Betül

2017-12-01

Two novel compounds, 3-[1-(2-fluoro-4-biphenyl)ethyl]-6-(4-fluorophenyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (C₂₃H₁₆F₂N₄S) (1) and 3-[1-(2-fluoro-4-biphenyl)ethyl]-6-(4-chlorophenyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (C₂₃H₁₆ClFN₄S) (2), have been designed and synthesized as cytotoxic agents. The compounds were characterized by infrared, proton nuclear magnetic resonance, mass spectral data, elemental analysis and X-ray powder diffraction. The present study comprises spectral data and crystal structures of these novel compounds determined from synchrotron X-ray powder diffraction data. The structure solutions were obtained by simulated annealing. The final structures were achieved by Rietveld refinement using soft restraints for all bond lengths, bond angles, and planar groups. Both compounds crystallize in space group1' mime-subtype='gif' type='simple'/>$P\\bar 1$,Z= 2, with the unit-cell parametersa= 6.37433(9),b= 11.3641(2),c= 14.09115(19) Å,α= 80.1740(8)°,β= 85.1164(8)°,γ= 80.9831(10)°,V= 991.55(3) ųof compound (1) anda= 6.53736(6),b= 11.55725(15),c= 14.01373(13) Å,α= 80.3323(7)°,β= 84.8939(6)°,γ= 79.3954(8)°,V= 1024.08(2) ųof compound (2). Structural analyses reveal that the title compounds are isostructural.

Risk model in stage IB1-IIB cervical cancer with positive node after radical hysterectomy

Directory of Open Access Journals (Sweden)

Chen Z

2016-05-01

Full Text Available Zhilan Chen,1,2,* Kecheng Huang,1,* Zhiyong Lu,1,3 Song Deng,1,4 Jiaqiang Xiong,1 Jia Huang,1 Xiong Li,5 Fangxu Tang,1 Zhihao Wang,6 Haiying Sun,1 Lin Wang,1 Shasha Zhou,1 Xiaoli Wang,1 Yao Jia,1 Ting Hu,1 Juan Gui,7 Dongyi Wan,1 Ding Ma,1 Shuang Li,1 Shixuan Wang11Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Techonology, Wuhan, 2Department of Obstetrics and Gynecology, Wuhan General Hospital of Guangzhou Military Command, Wuhan, 3Hubei Key Laboratory of Embryonic Stem Cell Research, Tai-He Hospital, Hubei University of Medicine, Shiyan, Hubei, 4Department of Obstetrics and Gynecology, University Hospital of Hubei University for Nationalities, Enshi, Hubei, 5Department of Obstetrics and Gynecology, Wuhan Central Hospital, Wuhan, 6Department of Pathology and Pathophysiology, Key Laboratory of Ministry of Education of China for Neurological Disorders, Huazhong University of Science and Techonology, Wuhan, 7Department of Obstetrics and Gynecology, Renmin Hospital, Wuhan University, Wuhan, People’s Republic of China*These authors contributed equally to this workAbstract: The purpose of this study was to identify risk factors in patients with surgically treated node-positive IB1-IIB cervical cancer and to establish a risk model for disease-free survival (DFS and overall survival (OS. A total of 170 patients who underwent radical hysterectomy and bilateral pelvic lymphadenectomy as primary treatment for node-positive International Federation of Gynaecology and Obstetrics (FIGO stage IB1-IIB cervical cancer from January 2002 to December 2008 were retrospectively analyzed. Five published risk models were evaluated in this population. The variables, including common iliac lymph node metastasis and parametrial invasion, were independent predictors of outcome in a multivariate analysis using a Cox regression model. Three distinct prognostic groups (low, intermediate, and high risk

Sleep Stage Transition Dynamics Reveal Specific Stage 2 Vulnerability in Insomnia.

Science.gov (United States)

Wei, Yishul; Colombo, Michele A; Ramautar, Jennifer R; Blanken, Tessa F; van der Werf, Ysbrand D; Spiegelhalder, Kai; Feige, Bernd; Riemann, Dieter; Van Someren, Eus J W

2017-09-01

Objective sleep impairments in insomnia disorder (ID) are insufficiently understood. The present study evaluated whether whole-night sleep stage dynamics derived from polysomnography (PSG) differ between people with ID and matched controls and whether sleep stage dynamic features discriminate them better than conventional sleep parameters. Eighty-eight participants aged 21-70 years, including 46 with ID and 42 age- and sex-matched controls without sleep complaints, were recruited through www.sleepregistry.nl and completed two nights of laboratory PSG. Data of 100 people with ID and 100 age- and sex-matched controls from a previously reported study were used to validate the generalizability of findings. The second night was used to obtain, in addition to conventional sleep parameters, probabilities of transitions between stages and bout duration distributions of each stage. Group differences were evaluated with nonparametric tests. People with ID showed higher empirical probabilities to transition from stage N2 to the lighter sleep stage N1 or wakefulness and a faster decaying stage N2 bout survival function. The increased transition probability from stage N2 to stage N1 discriminated people with ID better than any of their deviations in conventional sleep parameters, including less total sleep time, less sleep efficiency, more stage N1, and more wake after sleep onset. Moreover, adding this transition probability significantly improved the discriminating power of a multiple logistic regression model based on conventional sleep parameters. Quantification of sleep stage dynamics revealed a particular vulnerability of stage N2 in insomnia. The feature characterizes insomnia better than-and independently of-any conventional sleep parameter. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Treatment of patients with minimal stage IIIA Hodgkin's disease

International Nuclear Information System (INIS)

Powlis, W.D.; Mauch, P.; Goffman, T.; Goodman, R.L.

1987-01-01

Treatment recommendations for patients with upper abdominal Stage IIIA Hodgkin's (III1A) disease have varied widely. The current study reports on a combined institutional retrospective review of 85 patients with surgically staged III1A Hodgkin's disease. Twenty-two patients received combined modality therapy (CMT), 36 patients were treated initially with total nodal irradiation (TNI), and 27 with mantle and para-aortic radiotherapy (MPA). Patients treated with CMT had an actuarial 8-year freedom from relapse (FFR) of 96% as compared to a FFR of 51% in TNI treated patients (p = 0.002), and a FFR of 54% in MPA treated patients (p = 0.004). Of the 11 relapses in MPA treated patients, 7 had a component of their failure in the untreated pelvic or inguinal nodes. The patients treated with CMT had an 8-year actuarial survival of 100% as compared to 79% in TNI treated patients (p = 0.055) and 78% in patients treated with MPA (p = 0.025). Histology and the number of splenic nodules were the most important prognostic variables. Patients with MC/LD histology and greater than or equal to 5 splenic nodules have a high risk of relapse (10/13) when treated with radiation alone (TNI or MPA). We recommend CMT for this group of patients. Patients with NS/LP histology and 1-4 splenic nodules represent a favorable subset of Stage III1A patients. Only 4/21 patients have relapsed and all 21 patients are currently alive without disease regardless of treatment. We currently feel that patients with Stage III1A Hodgkin's disease with NS/LP histology and splenic disease limited to 1-4 nodules are good candidates for MPA as an alternative to TNI or CMT

Thermal decomposition of rhenium (5) complexes with 1,2,4-triazole

International Nuclear Information System (INIS)

Amindzhanov, A.A.; Gagieva, S.Ch.; Kotegov, K.V.

1991-01-01

Processes of thermal decomposition of rhenium (5) complexes with 1,2,4-triazole were studied. Thermolysis products were identified on the basis of data of the element analysis, IR spectra, conductometry and other methods. It is ascertained that at the first stage of thermolysis of hydroxyl-containing monomer complexes removal of water molecules occurs, and at the second one - dimerization process with formation of Re-O-Re group. It is shown that the nature of halide ion practically does not affect the temperature of the start of intensive thermal decomposition of the complexes

The Inhibitory Effect of Rapamycin on Toll Like Receptor 4 and Interleukin 17 in the Early Stage of Rat Diabetic Nephropathy

Directory of Open Access Journals (Sweden)

Ruichao Yu

2016-02-01

Full Text Available Background/Aims: There is increasing evidence showing that innate immune responses and inflammatory processes play an important role in the development and progression of diabetic nephropathy (DN. The potential effect of innate immunity in the early stage of DN is still unclear. Toll-Like-Receptor 4 (TLR4 is vigorously involved in the progress of kidney diseases in a sterile environment. The activation of the interleukin 17 (IL-17 pathway produces inflammatory cytokines, appearing in various kidney diseases. Unfortunately the relationship between TLR4 and IL-17 has not been investigated in diabetic nephropathy to date. The aim of this study is to investigate whether mammalian target of rapamycin (mTOR inhibition may be dependent on TLR4 signaling and the pro-inflammatory factor IL-17 to delay the progression of DN. Methods: Streptozotocin (STZ-induced diabetic rats were randomly assigned to 3 experimental groups: a diabetic nephropathy group (DN, n = 6; and a diabetic nephropathy treated with rapamycin group (Rapa, n = 6 and a control group (Control, n =6. Body weight, fasting blood sugar, and 24h urine albumin were assessed at week 2, week 4 and week 8. Renal tissues were harvested for H&E, PAS staining, as well as an immunohistochemistry assay for TLR4 and IL-17. TLR4 quantitative expression was measured by Western-Blot analysis and RT-PCR. Results: Our results demonstrated that the expression of both TLR4 and IL-17 were upregulated in early stage DN and reduced by rapamycin. TLR4 and IL-17 both increased and positively related to 24h urinary albumin and kidney/weight ratio. However, neither TLR4 nor IL-17 made a significant difference on fasting blood sugar. Conclusions: Taken together, our results confirm and extend previous studies identifying the significance of the TLR4 and Th17 pathways in development of early stage DN. Furthermore, we suggest this overexpression of TLR4 might be involved in the immunopathogenesis of DN through

Autoimmune gastritis: histology phenotype and OLGA staging.

Science.gov (United States)

Rugge, M; Fassan, M; Pizzi, M; Zorzetto, V; Maddalo, G; Realdon, S; De Bernard, M; Betterle, C; Cappellesso, R; Pennelli, G; de Boni, M; Farinati, F

2012-06-01

Among Western populations, the declining incidence of Helicobacter pylori infection coincides with a growing clinical impact of autoimmune gastritis. To describe the histological phenotype of autoimmune gastritis, also to test the prognostic impact of OLGA staging in the autoimmune setting. A single-institutional series (spanning the years 2003-2011) of 562 consecutive patients (M:F ratio: 1:3.7; mean age = 57.6 ± 14.4 years) with serologically confirmed autoimmune gastritis underwent histology review and OLGA staging. Helicobacter pylori infection was ascertained histologically in 44/562 cases (7.8%). Forty six biopsy sets (8.2%) featured OLGA stages III-IV; they included all four cases of incidental epithelial neoplasia (three intraepithelial and one invasive; three of these four cases had concomitant H. pylori infection). There were 230 (40.9%) and 139 (24.7%) cases, respectively, of linear and micro-nodular enterochromaffin-like cell hyperplasia; 19 (3.4%) type I carcinoids were detected. The series included 116 patients who underwent repeated endoscopy/biopsy sampling (mean time elapsing between the two procedures = 54 months; range 24-108). Paired histology showed a significant (P = 0.009) trend towards a stage progression [the stage increased in 25/116 cases (22%); it remained unchanged in 87/116 cases (75%)]. In autoimmune gastritis, the cancer risk is restricted to high-risk gastritis stages (III-IV), and is associated mainly with concomitant H. pylori infection. OLGA staging consistently depicts the time-dependent organic progression of the autoimmune disease and provides key information for secondary gastric cancer prevention strategies. © 2012 Blackwell Publishing Ltd.

NeoPalAna: Neoadjuvant palbociclib, a cyclin-dependent kinase 4/6 inhibitor, and anastrozole for clinical stage 2 or 3 estrogen receptor positive breast cancer

Science.gov (United States)

Ma, Cynthia X.; Gao, Feng; Luo, Jingqin; Northfelt, Donald W.; Goetz, Matthew; Forero, Andres; Hoog, Jeremy; Naughton, Michael; Ademuyiwa, Foluso; Suresh, Rama; Anderson, Karen S.; Margenthaler, Julie; Aft, Rebecca; Hobday, Timothy; Moynihan, Timothy; Gillanders, William; Cyr, Amy; Eberlein, Timothy J.; Hieken, Tina; Krontiras, Helen; Guo, Zhanfang; Lee, Michelle V.; Spies, Nicholas C.; Skidmore, Zachary L.; Griffith, Obi L.; Griffith, Malachi; Thomas, Shana; Bumb, Caroline; Vij, Kiran; Bartlett, Cynthia Huang; Koehler, Maria; Al-Kateb, Hussam; Sanati, Souzan; Ellis, Matthew J.

2017-01-01

Purpose Cyclin-dependent kinase (CDK) 4/6 drives cell proliferation in estrogen receptor positive (ER+) breast cancer. This single-arm phase II neoadjuvant trial (NeoPalAna) assessed the anti-proliferative activity of the CDK4/6 inhibitor palbociclib in primary breast cancer as a prelude to adjuvant studies. Experimental Design Eligible patients with clinical stage II/III ER+/HER2- breast cancer received anastrozole 1mg daily for 4 weeks (cycle 0) (with goserelin if premenopausal), followed by adding palbociclib (125mg daily on days 1-21) on cycle 1 day 1 (C1D1) for four 28-day cycles unless C1D15 Ki67>10%, in which case patients went off study due to inadequately response. Anastrozole was continued until surgery, which occurred 3-5 weeks post palbociclib exposure. Later patients received additional 10-12 days of palbociclib (Cycle 5) immediately before surgery. Serial biopsies at baseline, C1D1, C1D15, and surgery were analyzed for Ki67, gene expression and mutation profiles. The primary endpoint was Complete Cell Cycle Arrest (CCCA: central Ki67<2.7%). Results Fifty patients enrolled. The CCCA rate was significantly higher after adding palbociclib to anastrozole (C1D15 87% vs C1D1 26%, p<0.001). Palbociclib enhanced cell cycle control over anastrozole monotherapy regardless of luminal subtype (A vs B) and PIK3CA status with activity observed across a broad range of clinicopathological and mutation profiles. Ki67 recovery at surgery following palbociclib washout was suppressed by cycle 5 palbociclib. Resistance was associated with non-luminal subtypes and persistent E2F-target gene expression. Conclusions Palbociclib is an active anti-proliferative agent for early-stage breast cancer resistant to anastrozole, however, prolonged administration may be necessary to maintain its effect. PMID:28270497

Stage-specific analysis of plasma protein profiles in ovarian cancer: Difference in-gel electrophoresis analysis of pooled clinical samples

Directory of Open Access Journals (Sweden)

Mark J Bailey

2013-01-01

Full Text Available Introduction: Ovarian cancer is the leading cause of death from gynecological cancer. Non-specific symptoms early in disease and the lack of specific biomarkers hinder early diagnosis. Multi-marker blood screening tests have shown promise for improving identification of early stage disease; however, available tests lack sensitivity, and specificity. Materials and Methods: In this study, pooled deeply-depleted plasma from women with Stage 1, 2 or 3 ovarian cancer and healthy controls were used to compare the 2-dimensional gel electrophoresis (2-DE protein profiles and identify potential novel markers of ovarian cancer progression. Results/Discussion: Stage-specific variation in biomarker expression was observed. For example, apolipoprotein A1 expression is relatively low in control and Stage 1, but shows a substantial increase in Stage 2 and 3, thus, potential of utility for disease confirmation rather than early detection. A better marker for early stage disease was tropomyosin 4 (TPM4. The expression of TPM4 increased by 2-fold in Stage 2 before returning to "normal" levels in Stage 3 disease. Multiple isoforms were also identified for some proteins and in some cases, displayed stage-specific expression. An interesting example was fibrinogen alpha, for which 8 isoforms were identified. Four displayed a moderate increase at Stage 1 and a substantial increase for Stages 2 and 3 while the other 4 showed only moderate increases. Conclusion: Herein is provided an improved summary of blood protein profiles for women with ovarian cancer stratified by stage.

High performance 40-stage and 15-stage quantum cascade lasers based on two-material active region composition

Science.gov (United States)

Figueiredo, P.; Suttinger, M.; Go, R.; Todi, A.; Shu, Hong; Tsvid, E.; Patel, C. Kumar N.; Lyakh, A.

2017-05-01

5.6μm quantum cascade lasers based on Al0.78In0.22As/In0.69Ga0.31As active region composition with measured pulsed room temperature wall plug efficiency of 28.3% are reported. Injection efficiency for the upper laser level of 75% was measured by testing devices with variable cavity length. Threshold current density of 1.7kA/cm2 and slope efficiency of 4.9W/A were measured for uncoated 3.15mm x 9µm lasers. Threshold current density and slope efficiency dependence on temperature in the range from 288K to 348K can be described by characteristic temperatures T0 140K and T1 710K, respectively. Pulsed slope efficiency, threshold current density, and wallplug efficiency for a 2.1mm x 10.4µm 15-stage device with the same design and a high reflection-coated back facet were measured to be 1.45W/A, 3.1kA/cm2 , and 18%, respectively. Continuous wave values for the same parameters were measured to be 1.42W/A, 3.7kA/cm2 , and 12%. Continuous wave optical power levels exceeding 0.5W per millimeter of cavity length was demonstrated. When combined with the 40-stage device data, the inverse slope efficiency dependence on cavity length for 15-stage data allowed for separate evaluation of the losses originating from the active region and from the cladding layers of the laser structure. Specifically, the active region losses for the studied design were found to be 0.77cm-1, while cladding region losses - 0.33cm-1. The data demonstrate that active region losses in mid wave infrared quantum cascade lasers largely define total waveguide losses and that their reduction should be one of the main priorities in the quantum cascade laser design.

Evaluation of surgical staging prior to combined modality therapy for esophageal cancer

International Nuclear Information System (INIS)

Suntharalingam, M.; Vines, E.; Echo, D. van; Greenwald, B.; Krasna, M.

1996-01-01

OBJECTIVE: Historically, patients with esophageal cancer have had a poor outcome despite aggressive treatment approaches. Recently chemo/RT followed by surgical resection has shown a significant improvement in survival in this patient population. The success of this aggressive approach has been predicated on accurate definition of disease extent and appropriate patient selection. We have performed pre-treatment surgical staging (thoracoscopy and laparoscopy) on 38 pts. referred for management of their localized esophageal cancer. The purpose of this report is to compare the results of clinical (CT, MRI, EGD, EUS) vs. surgical staging. The data gathered prospectively will also be used to identify potential predictors for disease-free survival. METHODS: Thirty-eight pts. were treated with combined modality therapy prior to a planned surgical resection. Patients received 50.4 Gy in 1.8 Gy fractions in conjunction with 5 FU (1 Gm/m2) and Cisplatin (100 mg/m2) on days 1 and 28. Patients were evaluated 4 to 6 wks. after completion of therapy for consideration of Ivor-Lewis esophagectomy. Of the original 38 pts., 4 are awaiting surgery, 3 died prior to resection, 2 pts. progressed through chemo/RT, and 1 refused. To date, 28 pts. are available for analysis with a median follow up of 21.5 months. This group included 16 pts. with squamous cell and 12 with adenocarcinoma. RESULTS: Twenty-five of the 28 pts. taken to surgery have undergone pre treatment surgical staging (2 refused, 1 medically unfit). Evaluation of tumor status revealed noninvasive staging to be accurate 56% of the time. Five pts. were converted from T 2 to T 3 , 1 from T 3 to T 4 and 3 T 4 tumors were found to be T 3 . Using the surgical findings at time of staging, 6 pts. were found to have T 2 tumors, 16 had T 3 tumors, and 3 had T 4 tumors. Clinical lymph node status was confirmed in 15 patients (60%). Six went from N+ to N 0 and 4 pts. thought to be N 0 were N+. Eight patients had evidence of positive

High cost of stage IV pressure ulcers.

Science.gov (United States)

Brem, Harold; Maggi, Jason; Nierman, David; Rolnitzky, Linda; Bell, David; Rennert, Robert; Golinko, Michael; Yan, Alan; Lyder, Courtney; Vladeck, Bruce

2010-10-01

The aim of this study was to calculate and analyze the cost of treatment for stage IV pressure ulcers. A retrospective chart analysis of patients with stage IV pressure ulcers was conducted. Hospital records and treatment outcomes of these patients were followed up for a maximum of 29 months and analyzed. Costs directly related to the treatment of pressure ulcers and their associated complications were calculated. Nineteen patients with stage IV pressure ulcers (11 hospital-acquired and 8 community-acquired) were identified and their charts were reviewed. The average hospital treatment cost associated with stage IV pressure ulcers and related complications was $129,248 for hospital-acquired ulcers during 1 admission, and $124,327 for community-acquired ulcers over an average of 4 admissions. The costs incurred from stage IV pressure ulcers are much greater than previously estimated. Halting the progression of early stage pressure ulcers has the potential to eradicate enormous pain and suffering, save thousands of lives, and reduce health care expenditures by millions of dollars. Copyright © 2010 Elsevier Inc. All rights reserved.

COMPASS Final Report: Enceladus Solar Electric Propulsion Stage

Science.gov (United States)

Oleson, Steven R.; McGuire, Melissa L.

2011-01-01

The results of the NASA Glenn Research Center (GRC) COllaborative Modeling and Parametric Assessment of Space Systems (COMPASS) internal Solar Electric Propulsion (SEP) stage design are documented in this report (Figure 1.1). The SEP Stage was designed to deliver a science probe to Saturn (the probe design was performed separately by the NASA Goddard Space Flight Center s (GSFC) Integrated Mission Design Center (IMDC)). The SEP Stage delivers the 2444 kg probe on a Saturn trajectory with a hyperbolic arrival velocity of 5.4 km/s. The design carried 30 percent mass, 10 percent power, and 6 percent propellant margins. The SEP Stage relies on the probe for substantial guidance, navigation and control (GN&C), command and data handling (C&DH), and Communications functions. The stage is configured to carry the probe and to minimize the packaging interference between the probe and the stage. The propulsion system consisted of a 1+1 (one active, one spare) configuration of gimbaled 7 kW NASA Evolutionary Xenon Thruster (NEXT) ion propulsion thrusters with a throughput of 309 kg Xe propellant. Two 9350 W GaAs triple junction (at 1 Astronomical Unit (AU), includes 10 percent margin) ultra-flex solar arrays provided power to the stage, with Li-ion batteries for launch and contingency operations power. The base structure was an Al-Li hexagonal skin-stringer frame built to withstand launch loads. A passive thermal control system consisted of heat pipes to north and south radiator panels, multilayer insulation (MLI) and heaters for the Xe tank. All systems except tanks and solar arrays were designed to be single fault tolerant.

ChAd63-MVA-vectored blood-stage malaria vaccines targeting MSP1 and AMA1: assessment of efficacy against mosquito bite challenge in humans.

Science.gov (United States)

Sheehy, Susanne H; Duncan, Christopher J A; Elias, Sean C; Choudhary, Prateek; Biswas, Sumi; Halstead, Fenella D; Collins, Katharine A; Edwards, Nick J; Douglas, Alexander D; Anagnostou, Nicholas A; Ewer, Katie J; Havelock, Tom; Mahungu, Tabitha; Bliss, Carly M; Miura, Kazutoyo; Poulton, Ian D; Lillie, Patrick J; Antrobus, Richard D; Berrie, Eleanor; Moyle, Sarah; Gantlett, Katherine; Colloca, Stefano; Cortese, Riccardo; Long, Carole A; Sinden, Robert E; Gilbert, Sarah C; Lawrie, Alison M; Doherty, Tom; Faust, Saul N; Nicosia, Alfredo; Hill, Adrian V S; Draper, Simon J

2012-12-01

The induction of cellular immunity, in conjunction with antibodies, may be essential for vaccines to protect against blood-stage infection with the human malaria parasite Plasmodium falciparum. We have shown that prime-boost delivery of P. falciparum blood-stage antigens by chimpanzee adenovirus 63 (ChAd63) followed by the attenuated orthopoxvirus MVA is safe and immunogenic in healthy adults. Here, we report on vaccine efficacy against controlled human malaria infection delivered by mosquito bites. The blood-stage malaria vaccines were administered alone, or together (MSP1+AMA1), or with a pre-erythrocytic malaria vaccine candidate (MSP1+ME-TRAP). In this first human use of coadministered ChAd63-MVA regimes, we demonstrate immune interference whereby responses against merozoite surface protein 1 (MSP1) are dominant over apical membrane antigen 1 (AMA1) and ME-TRAP. We also show that induction of strong cellular immunity against MSP1 and AMA1 is safe, but does not impact on parasite growth rates in the blood. In a subset of vaccinated volunteers, a delay in time to diagnosis was observed and sterilizing protection was observed in one volunteer coimmunized with MSP1+AMA1-results consistent with vaccine-induced pre-erythrocytic, rather than blood-stage, immunity. These data call into question the utility of T cell-inducing blood-stage malaria vaccines and suggest that the focus should remain on high-titer antibody induction against susceptible antigen targets.

Effects of shifting growth stage and regulating temperature on seasonal variation of CH4 emission from rice

Science.gov (United States)

Watanabe, Akira; Yamada, Hiromi; Kimura, Makoto

2001-09-01

Seasonal variations in CH4 emission rates from rice paddies have been reported to have one or more maxima during the middle and late periods of rice growth. The factor affecting an appearance of CH4 emission maxima was examined in three types of pot experiments. In the experiment 1, four rice cultivars with difference in length of the period from transplanting to heading were transplanted on the same days. For the experiment 2, a cultivar was transplanted 4 times with interval of two weeks. In these experiments, the heading differed about a month between the earliest and latest treatments, respectively. However, shifting growth stage of rice plants did not shift the CH4 emission maxima, and the CH4 emission maxima often matched the maxima of daily mean air temperature. The effect of variation in temperature on CH4 emission rate was further investigated in the experiment 3 by placing the rice-planted pots under regulated temperature. Besides the first emission peak of CH4 attributable to rice straw (RS) carbon, three emission peaks corresponding to the peaks of air temperature were detected for the RS-applied pots placed outdoors. These three peaks were not observed or much less conspicuous for the RS-applied pots in a phytotron at 30°C. Temporal decreases in CH4 emission were detected both for the pots placed in the phytotron and outdoors just after the topdressing of (NH4)2SO4, which was considered to be a major cause of irregular disagreement between the variations in CH4 emission rates and in air temperature during the middle period of rice growth.

Crystal structures of three co-crystals of 1,2-bis-(pyridin-4-yl)ethane with 4-alk-oxy-benzoic acids: 4-eth-oxy-benzoic acid-1,2-bis-(pyridin-4-yl)ethane (2/1), 4-n-propoxybenzoic acid-1,2-bis(pyridin-4-yl)ethane (2/1) and 4-n-but-oxy-benzoic acid-1,2-bis-(pyridin-4-yl)ethane (2/1).

Science.gov (United States)

Tabuchi, Yohei; Gotoh, Kazuma; Ishida, Hiroyuki

2015-11-01

The crystal structures of three hydrogen-bonded co-crystals of 4-alk-oxy-benzoic acid-1,2-bis-(pyridin-4-yl)ethane (2/1), namely, 2C9H10O3·C12H12N2, (I), 2C10H12O3·C12H12N2, (II), and 2C11H14O3·C12H12N2, (III), have been determined at 93, 290 and 93 K, respectively. In (I), the asymmetric unit consists of one 4-eth-oxy-benzoic acid mol-ecule and one half-mol-ecule of 1,2-bis-(pyridin-4-yl)ethane, which lies on an inversion centre. In (II) and (III), the asymmetric units each comprise two crystallographically independent 4-alk-oxy-benzoic acid mol-ecules and one 1,2-bis-(pyridin-4-yl)ethane mol-ecule. In each crystal, the two components are linked by O-H⋯N hydrogen bonds, forming a linear hydrogen-bonded 2:1unit of the acid and the base. Similar to the structure of 2:1 unit of (I), the units of (II) and (III) adopt nearly pseudo-inversion symmetry. The 2:1 units of (I), (II) and (III) are linked via C-H⋯O hydrogen bonds, forming tape structures.

The protection motivation theory within the stages of the transtheoretical model - stage-specific interplay of variables and prediction of exercise stage transitions.

Science.gov (United States)

Lippke, Sonia; Plotnikoff, Ronald C

2009-05-01

Two different theories of health behaviour have been chosen with the aim of theory integration: a continuous theory (protection motivation theory, PMT) and a stage model (transtheoretical model, TTM). This is the first study to test whether the stages of the TTM moderate the interrelation of PMT-variables and the mediation of motivation, as well as PMT-variables' interactions in predicting stage transitions. Hypotheses were tested regarding (1) mean patterns, stage pair-comparisons and nonlinear trends using ANOVAs; (2) prediction-patterns for the different stage groups employing multi-group structural equation modelling (MSEM) and nested model analyses; and (3) stage transitions using binary logistic regression analyses. Adults (N=1,602) were assessed over a 6 month period on their physical activity stages, PMT-variables and subsequent behaviour. (1) Particular mean differences and nonlinear trends in all test variables were found. (2) The PMT adequately fitted the five stage groups. The MSEM revealed that covariances within threat appraisal and coping appraisal were invariant and all other constrains were stage-specific, i.e. stage was a moderator. Except for self-efficacy, motivation fully mediated the relationship between the social-cognitive variables and behaviour. (3) Predicting stage transitions with the PMT-variables underscored the importance of self-efficacy. Only when threat appraisal and coping appraisal were high, stage movement was more likely in the preparation stage. Results emphasize stage-specific differences of the PMT mechanisms, and hence, support the stage construct. The findings may guide further theory building and research integrating different theoretical approaches.

Post-operative high dose rate vaginal apex brachytherapy in stage I endometrial adenocarcinoma

International Nuclear Information System (INIS)

Gumbs, A.A.; Turner, B.C.; Knisely, J.P.S.; Kacinski, B.M.; Roberts, K.B.; Peschel, R.E.; Haffty, B.G.; Rutherford, T.J.; Edraki, B.; Schwartz, P.E.; Wilson, L.D.

1996-01-01

Purpose/Objective: Patients with Stage I endometrial adenocarcinoma have traditionally been treated with total abdominal hysterectomy/bilateral salpingo-oophorectomy and radiation. The reported incidence of local recurrence in surgically treated patients with FIGO Stage IA or IB endometrial adenocarcinoma is 4-10% at 2 years. Combined surgery and radiation has resulted in a reduction of recurrence to 2-6%. We report the presentation, actuarial survival, actuarial rate of local failure, salvage rate, and complications for patients undergoing high dose rate (HDR) vaginal apex brachytherapy following surgery. Materials and Methods: Between 1985 and 1994 a total of 286 patients with FIGO Stage I endometrioid uterine adenocarcinoma were treated with HDR Ir-192 vaginal apex brachytherapy alone to a total dose of 21 Gy in 3 fractions at 0.5 cm from the vaginal mucosa. The pathologic stage by treatment group was IA: 31%, IB: 68%, and IC: 1%. The histologic grade of the patient's tumors was grade 1: 69%, 2: 29%, and 3: 2% of patients. The median time from surgery to radiation was 34 days (range 14-66 days). The median follow-up for 286 patients with Stage IA (92 patients), IB (190 patients), and IC (4 patients) was respectively, 37, 35 and 40 months (2 patients lost to follow-up prior to 6 months). Results: Patients presented with vaginal bleeding (94%) or abnormal pap smear (6%) at a median age for Stage IA and IB, of 54 and 63 years, respectively (range 32-88). The 5-year overall actuarial survival rate was 94.5%. The 5-year actuarial survival rate by histologic grade was 97.5% and 91.5% for FIGO grade 1 and 2, respectively (p=.011). The 5-year actuarial survival rate by depth of myometrial invasion was 99.0% and 92.5% for Stage IA and IB, respectively (p=.029). Median overall time to failure is 19.5 months (range 10-36 months). The 5-year actuarial rate of local failure was 4.5%. The overall failure rate in our study group was 2.8% (8 patients), local failure only 1

The influence of CD 4+t cells, hiv disease stage and zidovudine on hiv isolation in Bahia, Brazil

Directory of Open Access Journals (Sweden)

Carlos Brites

1996-02-01

Full Text Available HIV-l isolation was attempted on 72 individuais, including persons with knoum HIV infection and five without proven HIV infection but with indeterminate Western blot patterns, as well as on low-risk HIV seronegative persons. The ahility to detect HIV- 1 frorn culture supernatant by p24 antigen capture assay was evaluated by segregating patients by absolute CD4+ cell counts, clinicai stage of disease, p24 antigenemia and zidovudine use. The likelihood of a p24 positive HIV culture was highest among patients with CD4+ T-cell counts below 200/ul and patients with advanced clinical disease. Use of zidovudine did not affect the rate ofHIV positwity in cultures.Tentativa de isolamento do vírus tipo 1 da imunodeficiência adquirida (VIH-1 foi realizada em 72 indivíduos sendo 51 pacientes com sorologia positiva para o VIH-1, confirmada por Western blot; 5 doadores de sangue com padrão indeterminado ao Western blot; 3 indivíduos com diagnóstico clínico de AIDS, porém com sorologia negativa, e 13 profissionais de saúde soronegativos. Os pacientes foram estratificados de acordo com a contagem de células CD4+, estágio clínico , antigenemia (p24 e uso de zidovudine. As culturas para o VIH-1 foram positivas em 45/50 (90% tentativas. Houve uma correlação inversa entre o número de células CD4+ e a freqüência de isolamento do VIH-1. As culturas foram positivas em 84% dos indivíduos com CD4+ <200, contra 48% d positividade naqueles com contagem de célula CD4+ acima deste valor. O uso de zidovudine não interferiu na positividade das culturas. Concluímo. que a sensibilidade dos métodos de culture qualitativo e quantitativo é similar para a detecção do VIH-1. A taxa de positividade das culturas não foi afetada pelo uso prévio de zidovudine, mas foi diretamente proporcional ao grau de imunodeficiência dos pacientes.

The contemporary role of 1 vs. 2-stage repair for proximal hypospadias.

Science.gov (United States)

Dason, Shawn; Wong, Nathan; Braga, Luis H

2014-12-01

This review discusses the most commonly employed techniques in the repair of proximal hypospadias, highlighting the advantages and disadvantages of single versus staged surgical techniques. Hypospadias can have a spectrum of severity with a urethral meatus ranging from the perineum to the glans. Associated abnormalities are commonly found with proximal hypospadias and encompass a large spectrum, including ventral curvature (VC) up to 50 degrees or more, ventral skin deficiency, a flattened glans, penile torsion and penoscrotal transposition. Our contemporary understanding of hypospadiology is comprised of a foundation built by experts who have described a number of techniques and their outcomes, combined with survey data detailing practice patterns. The two largest components of hypospadias repair include repair of VC and urethroplasty. VC greater than 20 degrees is considered clinically relevant to warrant surgical correction. To repair VC, the penis is first degloved-a procedure that may reduce or remove curvature by itself in some cases. Residual curvature is then repaired with dorsal plication techniques, transection of the urethral plate, and/or ventral lengthening techniques. Urethroplasty takes the form of 1- or 2-stage repairs. One-stage options include the tubularized incised urethroplasty (TIP) or various graft or flap-based techniques. Two-stage options also include grafts or flaps, including oral mucosal and preputial skin grafting. One stage repairs are an attractive option in that they may reduce cost, hospital stay, anesthetic risks, and time to the final result. The downside is that these repairs require mastery of multiple techniques may be more complex, and-depending on technique-have higher complication rates. Two-stage repairs are preferred by the majority of surveyed hypospadiologists. The 2-stage repair is versatile and has satisfactory outcomes, but necessitates a second procedure. Given the lack of clear high-quality evidence supporting the

Spleen dynamic contrast-enhanced magnetic resonance imaging as a new method for staging liver fibrosis in a piglet model.

Directory of Open Access Journals (Sweden)

Li Zhou

Full Text Available OBJECTIVE: To explore spleen hemodynamic alteration in liver fibrosis with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI, and to determine how to stage liver fibrosis with spleen DCE-MRI parameters. MATERIALS AND METHODS: Sixteen piglets were prospectively used to model liver fibrosis staged by liver biopsy, and underwent spleen DCE-MRI on 0, 5th, 9th, 16th and 21st weekend after modeling this disease. DCE-MRI parameters including time to peak (TTP, positive enhancement integral (PEI, maximum slope of increase (MSI and maximum slope of decrease (MSD of spleen were measured, and statistically analyzed to stage this disease. RESULTS: Spearman's rank correlation tests showed that TTP tended to increase with increasing stages of liver fibrosis (r = 0.647, P0.05, and decreased from stage 2 to 4 (P0.05. Mann-Whitney tests demonstrated that TTP and PEI could classify fibrosis between stage 0 and 1-4, between 0-1 and 2-4, between 0-2 and 3-4, or between 0-3 and 4 (all P<0.01. MSD could discriminate between 0-2 and 3-4 (P = 0.006, or between 0-3 and 4 (P = 0.012. MSI could not differentiate between any two stages. Receiver operating characteristic analysis illustrated that area under receiver operating characteristic curve (AUC of TTP was larger than of PEI for classifying stage ≥1 and ≥2 (AUC = 0.851 and 0.783, respectively. PEI could best classify stage ≥3 and 4 (AUC = 0.903 and 0.96, respectively. CONCLUSION: Spleen DCE-MRI has potential to monitor spleen hemodynamic alteration and classify liver fibrosis stages.

Automatic sleep stage classification based on EEG signals by using neural networks and wavelet packet coefficients.

Science.gov (United States)

Ebrahimi, Farideh; Mikaeili, Mohammad; Estrada, Edson; Nazeran, Homer

2008-01-01

Currently in the world there is an alarming number of people who suffer from sleep disorders. A number of biomedical signals, such as EEG, EMG, ECG and EOG are used in sleep labs among others for diagnosis and treatment of sleep related disorders. The usual method for sleep stage classification is visual inspection by a sleep specialist. This is a very time consuming and laborious exercise. Automatic sleep stage classification can facilitate this process. The definition of sleep stages and the sleep literature show that EEG signals are similar in Stage 1 of non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep. Therefore, in this work an attempt was made to classify four sleep stages consisting of Awake, Stage 1 + REM, Stage 2 and Slow Wave Stage based on the EEG signal alone. Wavelet packet coefficients and artificial neural networks were deployed for this purpose. Seven all night recordings from Physionet database were used in the study. The results demonstrated that these four sleep stages could be automatically discriminated from each other with a specificity of 94.4 +/- 4.5%, a of sensitivity 84.2+3.9% and an accuracy of 93.0 +/- 4.0%.

Radical (Wertheim) hysterectomy for early stages (1B and 2A ...

African Journals Online (AJOL)

A review of cases of early stages (1B & 2A) cancer of the cervix, managed by radical hysterectomy at Olabisi Onabanjo University Teaching Hospital Sagamu Nigeria between 1997 and 2004 was carried out to appraise the outcome in terms of the success and safety of the operation. Seventeen cases were so treated, and ...

Deformation of stages of exchange tower 12T1 - a case study (Paper No. 2.9)

International Nuclear Information System (INIS)

Gulati, B.S.

1992-01-01

Heavy Water Plant at Baroda is based on monothermal hydrogen ammonia exchange process. Exchange tower-12 T1 is the biggest vessel in the plant and has 12 exchange stages and a cable stage. During the annual shut-down in April-May 1991, tower was opened for maintenance when the 12th stage was lifted, frosting/icing was observed on its outer shell with some reported ammonia smell. This paper describes the incident, deformation of stages of exchange tower, possible causes of dent formation and also elaborates the remedial measures taken. (author). 6 figs

CT volumetric measurement of colorectal cancer helps predict tumor staging and prognosis.

Directory of Open Access Journals (Sweden)

Jin Young Park

Full Text Available To evaluate feasibility of CT colonography (CTC volumetry of colorectal cancer (CRC and its correlation with disease stage and patients' survival.CTC volumetry was performed for 126 patients who underwent preoperative CTC. Reproducibility of tumor volume (Tvol between two readers was assessed. One-way ANOVA and ROC analysis evaluated correlation between Tvol and pTNM staging. ROC analysis compared diagnostic performance to predict pTNM staging between Tvol and radiologist. Kaplan-Meier test compared overall survival.Reproducibility among readers was excellent (interclass correlation = 0.9829. Mean Tvol showed an incremental trend with T stage and Tvol of pT4b stage was significantly larger than other stages (P0.05. Smaller tumor burden (≤12.85cm3, ≤T3, N0, M0 stages, and curative surgery were significantly associated with patients' longer survival (P<0.05.CT volumetry has a limited value to predict N stage; however, it may outperform the radiologist's performance when predicting pT4b and M1b stage and can be a useful prognostic marker.

Neutral coordination polymers based on a metal-mono(dithiolene) complex: synthesis, crystal structure and supramolecular chemistry of [Zn(dmit)(4,4'-bpy)]n, [Zn(dmit)(4,4'-bpe)]n and [Zn(dmit)(bix)]n (4,4'-bpy = 4,4'-bipyridine, 4,4'-bpe = trans-1,2-bis(4-pyridyl)ethene, bix = 1,4-bis(imidazole-1-ylmethyl)-benzene.

Science.gov (United States)

Madhu, Vedichi; Das, Samar K

2011-12-28

This article describes a unique synthetic route that enables a neutral mono(dithiolene)metal unit, {Zn(dmit)}, to link with three different organic molecules, resulting in the isolation of a new class of neutral coordination polymers. The species {Zn(dmit)} coordinates with 4,4'-bipyridine (4,4'-bpy), trans-1,2-bis(4-pyridyl)ethene (4,4'-bpe) and 1,4-bis(imidazole-1-ylmethyl)-benzene (bix) as linkers giving rise to the formation of coordination polymers [Zn(dmit)(4,4'-bpy)](n) (1), [Zn(dmit)(4,4'-bpe)](n) (2) and [Zn(dmit)(bix)](n) (3) respectively. Compounds 1-3 were characterized by elemental analyses, IR, diffuse reflectance and single crystal X-ray diffraction studies. Compounds 1 and 3 crystallize in the monoclinic space group P2(1)/n, whereby compound 2 crystallizes in triclinic space group P1[combining macron]. In the present study, we chose three linkers 4,4'-bpy, 4,4'-bpe and bix (see , respectively, for their structural drawings), that differ in terms of their molecular dimensions. The crystal structures of compounds 1-3 are described here in terms of their supramolecular diversities that include π-π interactions, not only among aromatic stacking (compounds 1 and 3), but also between an aromatic ring and an ethylenic double bond (compound 2). The electronic absorption spectroscopy of compounds 1-3 support these intermolecular π-π interactions. This journal is © The Royal Society of Chemistry 2011

Serum Ionized Calcium Quantification for Staging Canine Periodontal Disease: A Preliminary Study.