tbuckley/cabot-search huggingface dataset:
First clinical experience with 17- estradiol-eluting biodivYsio matrix LO stent to prevent restenosis in de-novo native coronary arteries: Six-month clinical outcomes and angiographic follow-up from the EASTER trial
Authors: Alexandre A. Abizaid, Gishel New, Andrea S. Abizaid, Marco Costa, Vinicius Vaz, Nicholas Kipshidze, Rodolfo Staico, Fausto Feres, Roxana Mehran, Ibraim Pinto, Gary Roubin, Sriram Iyer, Jeffrey Moses, Martin Leon, Amanda Sousa, Jose Eduardo M. Sousa
Journal: Journal of the American College of Cardiology (2003)
Comparison of Liver Biopsy and Noninvasive Methods for Diagnosis of Hepatocellular Carcinoma
Authors: Eldad S. Bialecki, Amobi M. Ezenekwe, Elizabeth M. Brunt, Brian T. Collins, T. Brent Ponder, B. Kirke Bieneman, Adrian M. Di Bisceglie
Journal: Clinical Gastroenterology and Hepatology (2006)
Vitamin E Alleviates Renal Injury, but Not Hypertension, during Chronic Nitric Oxide Synthase Inhibition in Rats
Authors: Diana M. Attia, A. Marjan G. Verhagen, Erik S. G. Stroes, Ernst E. van Faassen, Hermann-Josef Gröne, Sjef J. De Kimpe, Hein A. Koomans, Branko Braam, Jaap A. Joles
Journal: Journal of the American Society of Nephrology (2001)

ABSTRACT. Chronic nitric oxide (NO) synthase inhibition in rats causes hypertension, renal vascular injury, and proteinuria. NO deficiency increases superoxide (O2−) activity, but the effects of antioxidant treatment on renal injury have not been studied in this model. Exposure of rats to Nω-nitro-L-arginine (L-NNA) for 4 d markedly decreased NO-dependent relaxation in aortic rings and increased glomerular and renal interstitial monocyte influx, but renal O2− activity was not increased. After 7 d, BP and proteinuria were significantly increased. After 21 d of L-NNA treatment, rats displayed severe hypertension, decreased GFR, marked proteinuria, glomerular ischemia, renal vascular and tubulointerstitial injury, and complete loss of NO-dependent relaxation. Renal O2− activity was markedly increased [lucigenin-enhanced chemiluminescence (LEC), 279 ± 71 versus 50 ± 7 counts/10 mg, P < 0.01; electron paramagnetic resonance spectroscopy, 0.57 ± 0.05 versus 0.34 ± 0.04 U/10 mg, P < 0.05]. Apocynin, a specific inhibitor of NADPH oxidase, and diphenyleneiodonium, an inhibitor of flavin-containing enzymes, completely inhibited LEC signals in vitro, whereas allopurinol had no effect, indicating that NAD(P)H oxidase plays a major role in superoxide production in the kidney. Endothelial function remained impaired during cotreatment with α-tocopherol and there was no effect on hypertension or tubulointerstitial injury, but glomerular ischemia, decreases in GFR, and renal vascular injury were prevented and proteinuria was ameliorated. Renal LEC signals were intermediate between control and L-NNA-alone values (181 ± 84 counts/10 mg). Chronic NO synthase inhibition in rats results in marked increases in renal cortical O2− activity, mediated by flavin-dependent oxidases. The absence of early increases in renal O2− activity, in the presence of endothelial dysfunction and macrophage influx, indicates that increased renal O2− activity is neither attributable to NO deficiency per se nor solely related to macrophage influx. The improvement of glomerular function and amelioration of renal vasculitis and proteinuria with vitamin E cotreatment indicate that oxidants are involved in the pathogenesis of renal injury in this model. However, markedly impaired endothelial function and unabated hypertension persist with vitamin E treatment and seem to be directly attributable to NO deficiency.
Antigen Presentation by Dendritic Cells In Vivo
Authors: Evelyne Mougneau, Stéphanie Hugues, Nicolas Glaichenhaus
Journal: The Journal of Experimental Medicine (2002)

Although dendritic cells (DCs) are known to be critical for inducing T cell immunity in immunized or infected individuals, it was recently proposed that DCs are also essential to silence potentially pathogenic self-reactive T cells that have escaped negative selection in the thymus ([1][1], [2][2
Cardiac output and renal blood flow in glycerol-induced acute renal failure in the rat.
Authors: C H Hsu, T W Kurtz, T P Waldinger
Journal: Circulation Research (1977)

Cardiac output (CO) and renal blood flow (RBF) were simultaneously evaluated by the microsphere method in water-drinking and chronic saline-drinking rats at 3, 12 and 24 hours after induction of acute renal failure by glycerol injection. Threee hours after glycerol injection CO and RBF decreased to 36% and 20% of the respective controls in water-drinking rats and to 41% and 24% of the controls in saline-drinking rats. Renal vascular resistance (RVR) increased significantly in both groups at this time. Isoncotic plasma expansion (3% of body weight) restored the RBF and RVR to normal in water-drinking rats 3 hours post-glycerol injection, althought CO increased to only 70% of the control. Twelve hours after glycerol injection, CO and RBF returned to normal in saline-drinking rats, whereas they remained lower than controls in water-drinking rats. Twenty-four hours post-glycerol injection, when acute renal failure was evident as indicated by blood urea nitrogen (BUN) values of 116.9 and 63.8 mg/100 ml in water- and saline-drinking rats, respectively, CO and RBF returned to normal, except that the CO of of water-drinking rats was slightly higher than control. Thus, we conclude that decreased CO is an important determinant of the early decrease in renal perfusion in glycerol-induced acute renal failure. Furthermore, the observed earlier return of CO and RBF to normal in saline-drinking rats may be partly responsible for reproducing the severity of acute renal failure.
Final Results of Phase III SYMMETRY Study: Randomized, Double-Blind Trial of Elesclomol Plus Paclitaxel Versus Paclitaxel Alone As Treatment for Chemotherapy-Naive Patients With Advanced Melanoma
Authors: Steven J. O'Day, Alexander M.M. Eggermont, Vanna Chiarion-Sileni, Richard Kefford, Jean Jacques Grob, Laurent Mortier, Caroline Robert, Jacob Schachter, Alessandro Testori, Jacek Mackiewicz, Philip Friedlander, Claus Garbe, Selma Ugurel, Frances Collichio, Wei Guo, Joelle Lufkin, Safi Bahcall, Vojo Vukovic, Axel Hauschild
Journal: Journal of Clinical Oncology (2013)

Elesclomol, an investigational first-in-class compound, induces oxidative stress, triggers mitochondrial-induced apoptosis in cancer cells, and shows synergy with taxanes in tumor models. Following completion of a phase II trial of elesclomol in combination with paclitaxel that met its primary end point of progression-free survival (PFS), this randomized, double-blind, controlled phase III study was conducted to confirm the efficacy and tolerability of elesclomol in combination with paclitaxel versus paclitaxel alone in patients with advanced melanoma.Patients with stage IV chemotherapy-naive melanoma (n = 651) were randomly assigned 1:1 to paclitaxel 80 mg/m(2) either alone or in combination with elesclomol 213 mg/m(2) administered weekly for 3 weeks of a 4-week cycle. Patients were stratified by prior systemic treatment, M1 subclass, and baseline lactate dehydrogenase (LDH) levels. The primary end point was PFS.The study did not achieve its PFS end point (hazard ratio, 0.89; P = .23). The study was stopped when an early overall survival data analysis indicated an imbalance in total deaths favoring paclitaxel, predominantly in patients with high LDH levels. A prospectively defined subgroup analysis revealed a statistically significant improvement in median PFS for the combination in patients with normal baseline LDH.The addition of elesclomol to paclitaxel did not significantly improve PFS in unselected patients with advanced melanoma. The association between baseline LDH and clinical outcomes suggests that LDH may be a predictive factor for treatment with this combination, consistent with recent findings on the association between elesclomol anticancer activity and cellular metabolic state.
Screening and Prostate-Cancer Mortality in a Randomized European Study
Authors: Fritz H. Schröder, Jonas Hugosson, Monique J. Roobol, Teuvo L.J. Tammela, Stefano Ciatto, Vera Nelen, Maciej Kwiatkowski, Marcos Lujan, Hans Lilja, Marco Zappa, Louis J. Denis, Franz Recker, Antonio Berenguer, Liisa Määttänen, Chris H. Bangma, Gunnar Aus, Arnauld Villers, Xavier Rebillard, Theodorus van der Kwast, Bert G. Blijenberg, Sue M. Moss, Harry J. de Koning, Anssi Auvinen
Journal: New England Journal of Medicine (2009)

The European Randomized Study of Screening for Prostate Cancer was initiated in the early 1990s to evaluate the effect of screening with prostate-specific-antigen (PSA) testing on death rates from prostate cancer.We identified 182,000 men between the ages of 50 and 74 years through registries in seven European countries for inclusion in our study. The men were randomly assigned to a group that was offered PSA screening at an average of once every 4 years or to a control group that did not receive such screening. The predefined core age group for this study included 162,243 men between the ages of 55 and 69 years. The primary outcome was the rate of death from prostate cancer. Mortality follow-up was identical for the two study groups and ended on December 31, 2006.In the screening group, 82% of men accepted at least one offer of screening. During a median follow-up of 9 years, the cumulative incidence of prostate cancer was 8.2% in the screening group and 4.8% in the control group. The rate ratio for death from prostate cancer in the screening group, as compared with the control group, was 0.80 (95% confidence interval [CI], 0.65 to 0.98; adjusted P=0.04). The absolute risk difference was 0.71 death per 1000 men. This means that 1410 men would need to be screened and 48 additional cases of prostate cancer would need to be treated to prevent one death from prostate cancer. The analysis of men who were actually screened during the first round (excluding subjects with noncompliance) provided a rate ratio for death from prostate cancer of 0.73 (95% CI, 0.56 to 0.90).PSA-based screening reduced the rate of death from prostate cancer by 20% but was associated with a high risk of overdiagnosis. (Current Controlled Trials number, ISRCTN49127736.)
Omega-3 polyunsaturated fatty acids for the treatment and prevention of colorectal cancer
Authors: A J Cockbain, G J Toogood, M A Hull
Journal: Gut (2011)

Omega (ω)-3 polyunsaturated fatty acids (PUFAs) are naturally occurring substances that are well tolerated and have been used extensively for the prevention of cardiovascular disease. More recently, ω-3 PUFAs have been recognised to have anticancer activity. There is also evidence suggesting improved efficacy and/or tolerability of conventional cancer chemotherapy when administered with ω-3 PUFAs. The purpose of this review is to (i) describe the mechanisms by which ω-3 PUFAs are thought to have antineoplastic activity, (ii) review published preclinical and clinical studies that support anti-colorectal cancer activity and (iii) summarise current clinical trials investigating the potential therapeutic role(s) of ω-3 PUFAs at different stages of colorectal carcinogenesis, from adenoma (polyp) prevention to treatment of established malignant disease and prevention of cancer recurrence.
17 -Estradiol induces protein S-nitrosylation in the endothelium
Authors: S. Chakrabarti, O. Lekontseva, A. Peters, S. T. Davidge
Journal: Cardiovascular Research (2009)

AimsEstrogen induces nitric oxide (NO) in the endothelium and appears to protect against inflammation and atherosclerosis. NO can induce post-translational protein modifications such as cysteine S-nitrosylation in the cellular proteins which may exert anti-inflammatory effects. However, whether estrogen can induce protein S-nitrosylation in the endothelium is not known. Given this background, we investigated the role of 17β-estradiol (E2β), the major form of estrogen in the body, on endothelial protein S-nitrosylation.
Intimal ultrastructure of human umbilical arteries. Observations on arteries from newborn children of smoking and nonsmoking mothers.
Authors: I Asmussen, K Kjeldsen
Journal: Circulation Research (1975)

The umbilical artery was chosen as a possible model for evaluating the vascular injury provoked by tobacco smoking in humans. Cords from newborn children delivered by 15 nonsmoking and 13 smoking mothers were studied in the transmission and the scanning electron microscope. Pronounced intimal changes were seen in the arteries from smoking mothers; the most important findings were degenerative changes of the endothelium such as swelling, blebbing, contraction, and subsequent opening of the endothelial junctions with formation of subendothelial edema. Other observations included dilation of the endoplasmic reticulum in the endothelium and reparative changes such as a considerable widening of the basement membrane. Since similar changes can be induced in arteries of animals by exposure to carbon monoxide or perfusion with nicotine, we conclude that the present study supports the concept that tobacco smoking is harmful to the vascular endothelium. This study also contributes to an understanding of the mechanism through which vascular injury is provoked in heavy smokers.
Angiotensin-Converting Enzyme Inhibitors Downregulate Tissue Factor Synthesis in Monocytes
Authors: Emanuela Napoleone, Angelomaria Di Santo, Marina Camera, Elena Tremoli, Roberto Lorenzet
Journal: Circulation Research (2000)

Abstract —Angiotensin-converting enzyme (ACE) inhibitors reduce the risk of recurrent myocardial infarction in patients with left ventricular dysfunction. Tissue factor (TF), the initiator of blood coagulation, plays a pivotal role in arterial thrombosis that occurs after atherosclerotic plaque fissuring. Because monocytes synthesize TF and contain several components of the renin-angiotensin system, we investigated the possibility that ACE inhibitors could modulate monocyte TF expression. Mononuclear leukocytes from healthy volunteers were incubated with endotoxin in the presence or absence of different ACE inhibitors. Captopril reduced TF expression in endotoxin-stimulated mononuclear leukocytes, as measured by a 1-stage clotting assay and ELISA analysis, by ≈60%. The effect was dose-dependent and was attributable to ACE inhibition, given that other ACE inhibitors, such as idrapril or fosinopril, and losartan, an antagonist of the angiotensin II AT 1 receptor, caused a comparable reduction in TF activity. Reverse transcriptase–polymerase chain reaction indicated that endotoxin-mediated increased levels of TF mRNA were inhibited by ACE inhibitors. Moreover, endotoxin-induced nuclear factor-κB translocation to the promoter region of the gene encoding for TF was markedly inhibited by captopril. The finding that ACE inhibitors and angiotensin II AT 1 antagonists can potentially modulate TF expression by mononuclear cells has important biological and therapeutic implications for the evolution of thrombi. Our results suggest that the anti-ischemic effect of these drugs might be explained, at least in part, by their ability to reduce TF expression in monocytes.
Migration, sexual behaviour, and HIV risk: a general population cohort in rural South Africa
Authors: Nuala McGrath, Jeffrey W Eaton, Marie-Louise Newell, Victoria Hosegood
Journal: The Lancet HIV (2015)

BackgroundIncreased sexual risk behaviour and HIV prevalence have been reported in migrants compared with non-migrants in sub-Saharan Africa. We investigated the association of residential and migration patterns with sexual HIV risk behaviours and HIV prevalence in an open, general population cohort in rural KwaZulu-Natal, South Africa.MethodsIn a mainly rural demographic surveillance area in northern KwaZulu-Natal, South Africa, we collected longitudinal demographic, migration, sexual behaviour, and HIV status data through household surveillance twice per year and individual surveillance once per year. All resident household members and a sample of non-resident household members (stratified by sex and migration patterns) were eligible for participation. Participants reported sexual risk behaviours, including data for multiple, concurrent, and casual sexual partners and condom use, and gave a dried blood spot sample via fingerprick for HIV testing. We investigated population-level differences in sexual HIV risk behaviours and HIV prevalence with respect to migration indicators using logistic regression models.FindingsBetween Jan 1, 2005, and Dec 31, 2011, the total eligible population at each surveillance round ranged between 21 129 and 22 726 women (aged 17–49 years) and between 20 399 and 22 100 men (aged 17–54 years). The number of eligible residents in any round ranged from 24 395 to 26 664 and the number of eligible non-residents ranged from 17 002 to 18 891 between rounds. The stratified sample of non-residents included between 2350 and 3366 individuals each year. Sexual risk behaviours were significantly more common in non-residents than in residents for both men and women. Estimated differences in sexual risk behaviours, but not HIV prevalence, varied between the migration indicators: recent migration, mobility, and migration type. HIV prevalence was significantly increased in current residents with a recent history of migration compared with other residents in the study area in men (adjusted odds ratio 1·19, 95% CI 1·07–1·33) and in women (1·18, 1·10–1·26).InterpretationLocal information about migrants and highly mobile individuals could help to target intervention strategies that are based on the identification of transmission hotspots.FundingWellcome Trust.
Activation of Transforming Growth Factor β by Malaria Parasite-derived Metalloproteinases and a Thrombospondin-like Molecule
Authors: Fakhreldin M. Omer, J. Brian de Souza, Patrick H. Corran, Ali A. Sultan, Eleanor M. Riley
Journal: The Journal of Experimental Medicine (2003)

Much of the pathology of malaria is mediated by inflammatory cytokines (such as interleukin 12, interferon γ, and tumor necrosis factor α), which are part of the immune response that kills the parasite. The antiinflammatory cytokine transforming growth factor (TGF)-β plays a crucial role in preventing the severe pathology of malaria in mice and TGF-β production is associated with reduced risk of clinical malaria in humans. Here we show that serum-free preparations of Plasmodium falciparum, Plasmodium yoelii 17XL, and Plasmodium berghei schizont-infected erythrocytes, but not equivalent preparations of uninfected erythrocytes, are directly able to activate latent TGF-β (LatTGF-β) in vitro. Antibodies to thrombospondin (TSP) and to a P. falciparum TSP-related adhesive protein (PfTRAP), and synthetic peptides from PfTRAP and P. berghei TRAP that represent homologues of TGF-β binding motifs of TSP, all inhibit malaria-mediated TGF-β activation. Importantly, TRAP-deficient P. berghei parasites are less able to activate LatTGF-β than wild-type parasites and their replication is attenuated in vitro. We show that activation of TGF-β by malaria parasites is a two step process involving TSP-like molecules and metalloproteinase activity. Activation of LatTGF-β represents a novel mechanism for direct modulation of the host response by malaria parasites.
THE CLASSIFICATION OF INDUSTRIAL APPLICANTS
Authors: A W. STEARNS
Journal: American Journal of Psychiatry (1920)

From the foregoing it will be seen that each man was graded according to the navy standard on a basis of 1, 2, 3, 4, as follows: Mentally: 1. Inferior. 2. Low average. 3. High average. 4. Superior. Educationally: 1. Less than eighth grade. 2. Eighth grade graduate. 3. High school students. 4. College. Industrially: 1. Misfits or failures. 2. Unskilled. 3. Experienced. 4. Skilled. In addition, each occupation was given a serial number from 1 to 53. This made it possible to give every man a numerical formula representing his capacity and training. The serial number representing his occupation was put at the right of a decimal point as it denotes a qualitative factor, the others being quantitative. For instance, 444.4 would represent a man of superior intelligence, college education and highly skilled, his occupation being an attorney. Also 111.34 would mean inferior intelligence, less than eighth grade education and industrial failure, his work being odd jobs. This enables a simple index, making it possible to locate and evaluate men easily. Also each number serves as a check upon the other, as a man with a 4 in his formula must be taken seriously, and a I means that he should be suspected of incapacity. As a matter of fact the formulas are very consistent, it being rare to find both a I and a 4 in the same formula.
Clinical Features and Histology of Apolipoprotein L1-Associated Nephropathy in the FSGS Clinical Trial
Authors: Jeffrey B. Kopp, Cheryl A. Winkler, Xiongce Zhao, Milena K. Radeva, Jennifer J. Gassman, Vivette D. D’Agati, Cynthia C. Nast, Changli Wei, Jochen Reiser, Lisa M. Guay-Woodford, Martin R. Pollak, Friedhelm Hildebrandt, Marva Moxey-Mims, Debbie S. Gipson, Howard Trachtman, Aaron L. Friedman, Frederick J. Kaskel
Journal: Journal of the American Society of Nephrology (2015)

Genetic variants in apolipoprotein L1 (APOL1) confer risk for kidney disease. We sought to better define the phenotype of APOL1-associated nephropathy. The FSGS Clinical Trial involved 138 children and young adults who were randomized to cyclosporin or mycophenolate mofetil plus pulse oral dexamethasone with a primary outcome of proteinuria remission. DNA was available from 94 subjects who were genotyped for APOL1 renal risk variants, with two risk alleles comprising the risk genotype. Two APOL1 risk alleles were present in 27 subjects, of whom four subjects did not self-identify as African American, and 23 of 32 (72%) self-identified African Americans. Individuals with the APOL1 risk genotype tended to present at an older age and had significantly lower baseline eGFR, more segmental glomerulosclerosis and total glomerulosclerosis, and more tubular atrophy/interstitial fibrosis. There were differences in renal histology, particularly more collapsing variants in those with the risk genotype (P=0.02), although this association was confounded by age. APOL1 risk genotype did not affect response to either treatment regimen. Individuals with the risk genotype were more likely to progress to ESRD (P<0.01). In conclusion, APOL1 risk genotypes are common in African-American subjects with primary FSGS and may also be present in individuals who do not self-identify as African American. APOL1 risk status is associated with lower kidney function, more glomerulosclerosis and interstitial fibrosis, and greater propensity to progress to ESRD. The APOL1 risk genotype did not influence proteinuria responses to cyclosporin or mycophenolate mofetil/dexamethasone.