tbuckley/cabot-search huggingface dataset:
Mifepristone Induces Growth Arrest, Caspase Activation, and Apoptosis of Estrogen Receptor-Expressing, Antiestrogen-Resistant Breast Cancer Cells
Authors: Virgil T. Gaddy, John T. Barrett, Jennifer N. Delk, Andre M. Kallab, Alan G. Porter, Patricia V. Schoenlein
Journal: Clinical Cancer Research (2004)

A major clinical problem in the treatment of breast cancer is the inherent and acquired resistance to antiestrogen therapy. In this study, we sought to determine whether antiprogestin treatment, used as a monotherapy or in combination with antiestrogen therapy, induced growth arrest and active cell death in antiestrogen-resistant breast cancer cells.MCF-7 sublines were established from independent clonal isolations performed in the absence of drug selection and tested for their response to the antiestrogens 4-hydroxytamoxifen (4-OHT) and ICI 182,780 (fulvestrant), and the antiprogestin mifepristone (MIF). The cytostatic (growth arrest) effects of the hormones were assessed with proliferation assays, cell counting, flow cytometry, and a determination of the phosphorylation status of the retinoblastoma protein. The cytotoxic (apoptotic) effects were analyzed by assessing increases in caspase activity and cleavage of poly(ADP-ribose) polymerase.All of the clonally derived MCF-7 sublines expressed estrogen receptor and progesterone receptor but showed a wide range of antiestrogen sensitivity, including resistance to physiological levels of 4-OHT. Importantly, all of the clones were sensitive to the antiprogestin MIF, whether used as a monotherapy or in combination with 4-OHT. MIF induced retinoblastoma activation, G(1) arrest, and apoptosis preceded by caspase activation.We demonstrate that: (a) estrogen receptor(+)progesterone receptor(+), 4-OHT-resistant clonal variants can be isolated from an MCF-7 cell line in the absence of antiestrogen selection; and (b) MIF and MIF plus 4-OHT combination therapy induces growth arrest and active cell death of the antiestrogen-resistant breast cancer cells. These preclinical findings show potential for a combined hormonal regimen of an antiestrogen and an antiprogestin to combat the emergence of antiestrogen-resistant breast cancer cells and, ultimately, improve the therapeutic index of antiestrogen therapy.
Sign of Leser-Trelat in a heart transplant recipient
Authors: C. Hsu, S. Abraham, A. Campanelli, J-H. Saurat, V. Piguet
Journal: British Journal of Dermatology (2005)

Journal Article Sign of Leser‐Trélat in a heart transplant recipient Get access C. Hsu, C. Hsu Department of Dermatology and Venereology, University Hospital of Geneva, HUG, 4‐752, 24 Rue Micheli‐du‐Crest, 1211 Geneva, Switzerland Search for other works by this author on: Oxford Academic Google Scholar S. Abraham, S. Abraham Department of Dermatology and Venereology, University Hospital of Geneva, HUG, 4‐752, 24 Rue Micheli‐du‐Crest, 1211 Geneva, Switzerland Search for other works by this author on: Oxford Academic Google Scholar A. Campanelli, A. Campanelli Department of Dermatology and Venereology, University Hospital of Geneva, HUG, 4‐752, 24 Rue Micheli‐du‐Crest, 1211 Geneva, Switzerland Search for other works by this author on: Oxford Academic Google Scholar J‐H. Saurat, J‐H. Saurat Department of Dermatology and Venereology, University Hospital of Geneva, HUG, 4‐752, 24 Rue Micheli‐du‐Crest, 1211 Geneva, Switzerland Search for other works by this author on: Oxford Academic Google Scholar V. Piguet V. Piguet Department of Dermatology and Venereology, University Hospital of Geneva, HUG, 4‐752, 24 Rue Micheli‐du‐Crest, 1211 Geneva, Switzerland Vincent Piguet MD PhD. E‐mail: vincent.piguet@medecine.unige.ch Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 153, Issue 4, 1 October 2005, Pages 861–862, https://doi.org/10.1111/j.1365-2133.2005.06850.x Published: 01 October 2005
Effect of tauroursodeoxycholic acid on bile-acid-induced apoptosis and cytolysis in rat hepatocytes
Authors: Christine Benz, Sabine Angermüller, Ulrich Töx, Petra Klöters-Plachky, Hans-Dieter Riedel, Peter Sauer, Wolfgang Stremmel, Adolf Stiehl
Journal: Journal of Hepatology (1998)
Potential benefits and hazards of physical activity and exercise on the gastrointestinal tract
Authors: H P F PETERS
Journal: Gut (2001)

This review describes the current state of knowledge on the hazards of exercise and the potential benefits of physical activity on the gastrointestinal tract. In particular, acute strenuous exercise may provoke gastrointestinal symptoms such as heartburn or diarrhoea. A substantial part (20–50%) of endurance athletes are hampered by these symptoms which may deter them from participation in training and competitive events. Nevertheless, these acute symptoms are transient and do not hamper the athlete9s health in the long term. The only exception is repeated gastrointestinal bleeding during training and competition, which in the long term may occasionally lead to iron deficiency and anaemia. In contrast, repetitive exercise periods at a relatively low intensity may have protective effects on the gastrointestinal tract. There is strong evidence that physical activity reduces the risk of colon cancer by up to 50%. Less convincing evidence exists for cholelithiasis and constipation. Physical activity may reduce the risk of diverticulosis, gastrointestinal haemorrhage, and inflammatory bowel disease although this cannot be substantiated firmly. Up to now, underlying mechanisms are poorly understood although decreased gastrointestinal blood flow, neuro-immuno-endocrine alterations, increased gastrointestinal motility, and mechanical bouncing during exercise are postulated. Future research on exercise associated digestive processes should give more insight into the relationship between physical activity and the function of the gastrointestinal tract.
Clinical Efficacy and Safety of Combined Mometasone Furoate and Formoterol in Patients With Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD)
Authors: E. Kerwin, D.P. Tashkin, C.E. Matiz-Bueno, D.E. Doherty, T. Shekar, S. Banerjee, B. Knorr, H. Staudinger
Journal: Journal of Allergy and Clinical Immunology (2012)
ANTIGENICITY OF POLYPEPTIDES (POLY ALPHA AMINO ACIDS)
Authors: Paul Pinchuck, Paul H. Maurer
Journal: The Journal of Experimental Medicine (1965)

The response of mice to synthetic linear polypeptides of known composition but random sequence has been studied. Neither Swiss mice nor a number of inbred strains could respond to copolymers of only 2 amino acids (G60L40, G60A40, G90T10). Upon introduction of as little as 4 mole per cent of a third amino acid, good immune responses were obtained, regardless of the nature of the third amino acid. The level of the immune response to a series of glu-lys-ala polymers increased with increasing alanine content of the polymer.
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): A Multiorgan Antiviral T Cell Response
Authors: Damien Picard, Baptiste Janela, Vincent Descamps, Michel D’Incan, Philippe Courville, Serge Jacquot, Sylvie Rogez, Laurent Mardivirin, Hélène Moins-Teisserenc, Antoine Toubert, Jacques Benichou, Pascal Joly, Philippe Musette
Journal: Science Translational Medicine (2010)

A dangerous drug reaction may be caused by a severe immune response to reactivated resident herpes viruses.
KRN8602 (MX2-Hydrochloride): An Active New Agent for the Treatment of Recurrent High-Grade Glioma
Authors: Kerrie Clarke, Russell L. Basser, Craig Underhill, Peter Mitchell, Jane Bartlett, Lawrence Cher, Michael Findlay, David Dalley, Malcolm Pell, Michael Byrne, Howard Geldard, John S. Hill, Darryl Maher, Richard M. Fox, Michael D. Green, Andrew H. Kaye
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To assess the efficacy and toxicity of KRN8602 when administered as an intravenous bolus to patients with recurrent high-grade malignant glioma. PATIENTS AND METHODS: Patients with recurrent or persistent anaplastic astrocytoma or glioblastoma multiforme who had not received recent chemotherapy or radiotherapy and were of good performance status (Eastern Cooperative Oncology Group score ≤ 2) were treated with an intravenous bolus of 40 mg/m 2 KRN8602 every 28 days. Tumor responses were assessed radiologically and clinically after every second cycle of therapy. Treatment was continued until documented progression or a total of six cycles. RESULTS: A median of three cycles (range, one to six cycles) of KRN8602 was administered to 55 patients, 49 of whom received at least two cycles and were, therefore, assessable for response. The overall response rate (disease stabilization or better) was 43% (95% confidence interval, 29% to 58%). There were three complete responses, one partial response, seven minor responses, and 10 patients with stable disease. The median time to progression was 2 months (range, 1.5 to 37 months) and overall survival was 11 months (range, 1.5 to 40 months). Neutropenia was the most common toxicity, although it was generally of brief duration, and there were only seven episodes of febrile neutropenia in 176 cycles delivered. Nonhematologic toxicity was mostly gastrointestinal (nausea and vomiting, diarrhea) and events were grade 2 or lower except for a single episode of grade 3 vomiting. CONCLUSION: KRN8602 is an active new agent with minimal toxicity in the treatment of relapsed or refractory high-grade glioma. Further studies with KRN8602 in combination with other cytotoxics and in adjuvant treatment of gliomas are warranted.
CD8+ cell anti-HIV activity correlates with the clinical state of the infected individual.
Authors: C E Mackewicz, H W Ortega, J A Levy
Journal: Journal of Clinical Investigation (1991)

The extent of antiviral activity exhibited in vitro by CD8+lymphocytes from individuals infected by HIV-1 correlates significantly with their clinical status. CD8+ lymphocytes from asymptomatic subjects were found to inhibit HIV-1 replication by 90% or greater at effector/target (E/T) ratios ranging from as low as 0.05 to 0.25. CD8+ cells from 17 of 19 (89%) of these subjects suppressed replication at an E/T ratio of 0.10 or less. CD8+ lymphocytes from symptomatic patients (non-AIDS) inhibited HIV-1 replication at E/T ratios ranging from 0.05 to 1.0, and CD8+ cells from 8 of 13 (62%) required ratios greater than 0.10. As a group, patients with AIDS exhibited the lowest degree of anti-HIV activity with their CD8+ lymphocytes. The effective range of E/T ratios from AIDS patients was 0.10-2.0, and 9 of 10 (90%) required E/T ratios greater than 0.25. This anti-HIV activity exhibited by CD8+ cells also correlated significantly with the subject's peripheral blood CD4+ cell count. The relative extent of CD8+ cell anti-HIV-1 activity was not found dependent on variations in the CD4+ target cells and viruses used. These findings suggest that the decreased CD8+ cell antiviral activity is related to progression to disease in HIV-infected individuals.
Suicide Trends Among Elementary School–Aged Children in the United States From 1993 to 2012
Authors: Jeffrey A. Bridge, Lindsey Asti, Lisa M. Horowitz, Joel B. Greenhouse, Cynthia A. Fontanella, Arielle H. Sheftall, Kelly J. Kelleher, John V. Campo
Journal: JAMA Pediatrics (2015)

Suicide is a leading cause of death among school-aged children younger than 12 years but little is known about the epidemiology of suicide in this age group.To describe trends in suicide among US children younger than 12 years by sociodemographic group and method of death.Period trend analysis of national mortality data on suicide in children aged 5 to 11 years in the United States from January 1, 1993, to December 31, 2012. Data were analyzed per 5-year periods, between 1993 to 1997 and 2008 to 2012.Number of suicide deaths and crude suicide rates. Period trends in rates of suicide were estimated using negative binomial regression incidence rate ratios (IRRs).The overall suicide rate among children aged 5 to 11 years remained stable between 1993 to 1997 and 2008 to 2012 (from 1.18 to 1.09 per 1 million; IRR = 0.96; 95% CI, 0.90-1.03). However, the suicide rate increased significantly in black children (from 1.36 to 2.54 per 1 million; IRR = 1.27; 95% CI, 1.11-1.45) and decreased in white children (from 1.14 to 0.77 per 1 million; IRR = 0.86; 95% CI, 0.79-0.94). The overall firearm suicide rate (IRR = 0.69; 95% CI, 0.57-0.85) and firearm suicide rate among white boys (IRR = 0.72; 95% CI, 0.59-0.88) decreased significantly during the study. The rate of suicide by hanging/suffocation increased significantly in black boys (IRR = 1.35; 95% CI, 1.14-1.61), although the overall change in suicide rates by hanging/suffocation or other suicide methods did not change during the study.The stable overall suicide rate in school-aged children in the United States during 20 years of study obscured a significant increase in suicide incidence in black children and a significant decrease in suicide incidence among white children. Findings highlight a potential racial disparity that warrants attention. Further studies are needed to monitor these emerging trends and identify risk, protective, and precipitating factors relevant to suicide prevention efforts in children younger than 12 years.
Anti-liver-kidney microsome antibody recognizes a 50,000 molecular weight protein of the endoplasmic reticulum.
Authors: F Alvarez, O Bernard, J C Homberg, G Kreibich
Journal: The Journal of Experimental Medicine (1985)

Children with autoimmune chronic active hepatitis may have high titers of antibodies detected by immunofluorescence staining of hepatocytes and tubular cells in rat liver and kidney sections, respectively. These antibodies are directed against antigens contained in microsomal fractions prepared from these two organs. We have found that sera from these patients recognized a 50,000 mol wt protein present in higher concentration in smooth microsome subfractions compared with rough microsome subfractions. This protein is an integral membrane protein and is not glycosylated. It is exposed on the cytoplasmic face of the endoplasmic reticulum and is rather resistant to proteolysis with proteinase K. Since patients with liver disease of different etiology and similar severity of cell lysis do not give rise to liver-kidney microsome antibody (LKMA), lysis of hepatocytes is apparently not a sufficient condition for their development.
Genetic Risk of Progression to Type 2 Diabetes and Response to Intensive Lifestyle or Metformin in Prediabetic Women With and Without a History of Gestational Diabetes Mellitus
Authors: Shannon D. Sullivan, Kathleen A. Jablonski, Jose C. Florez, Dana Dabelea, Paul W. Franks, Sam Dagogo-Jack, Catherine Kim, William C. Knowler, Costas A. Christophi, Robert Ratner
Journal: Diabetes Care (2013)

OBJECTIVE The Diabetes Prevention Program (DPP) trial investigated rates of progression to diabetes among adults with prediabetes randomized to treatment with placebo, metformin, or intensive lifestyle intervention. Among women in the DPP, diabetes risk reduction with metformin was greater in women with prior gestational diabetes mellitus (GDM) compared with women without GDM but with one or more previous live births. RESEARCH DESIGN AND METHODS We asked if genetic variability could account for these differences by comparing β-cell function and genetic risk scores (GRS), calculated from 34 diabetes-associated loci, between women with and without histories of GDM. RESULTS β-Cell function was reduced in women with GDM. The GRS was positively associated with a history of GDM; however, the GRS did not predict progression to diabetes or modulate response to intervention. CONCLUSIONS These data suggest that a diabetes-associated GRS is associated with development of GDM and may characterize women at risk for development of diabetes due to β-cell dysfunction.
Relationship between student: athlete satisfaction and leadership profiles of sport administrators in Nigerian Universities
Authors: Musa Garba Yakasat, Venkateshwarlu Kankanala
Journal: British Journal of Sports Medicine (2010)

Sports in the Nigerian Universities are essentially for students and by students. This means that the student is not only the prime beneficiary but also a prime producer of sports as entertainment in the university. Therefore the success of the university athletic programme depends on the satisfaction that students derive from sports. This study was conducted to find out the relationship between students-athletes' satisfaction and leadership profile of sports administrators in Nigerian Universities. To achieve the purpose a self-developed and validated questionnaire on students-athletes' satisfaction on leadership profiles of sports administrators was administered on the 700 randomly selected student-athletes from 14 Nigerian Universities. The part of the questionnaire on leadership profile was based on multifactor leadership questionnaire and the part of the questionnaire on student-athletes' satisfaction was based on the facets of athlete satisfaction questionnaire. Positive results were obtained on and team outcomes as well as individual processes of student-athlete satisfaction. The study also showed significant correlations among individual and team processes, as well as individual and team outcomes. The results showed that sports administrators of Nigerian Universities has transformational leadership profile more that translational and non-leadership profiles. The results further revealed significant correlations of transformational leadership, transactional leadership and non-leadership profiles with individual outcomes, team outcomes, individual processes of student-athletes; which were more than 44, explaining more than 42% of the variance in athletes' satisfaction.
Twenty-five Years of Breast Cancer Risk Models and Their Applications
Authors: M. H. Gail
Journal: JNCI Journal of the National Cancer Institute (2015)

I would like to thank the editors for the invitation to comment on “Projecting Individualized Probabilities of Developing Breast Cancer for White Females Who Are Being Examined Annually” (1) and to recognize coauthors of that article, Louise A. Brinton, David P. Byar, Donald K. Corle, Sylvan B. Green, Catherine Schairer, and John J. Mulvihill, who contributed key insights and analyses.

Several features may explain the frequent citations to this paper. 1) It focused on a clinically crucial quantity, absolute risk, namely the probability that a woman with specific risk factors will develop breast cancer over a defined age interval, with allowance for competing risks. 2) Breast cancer is a common cancer for which preventive interventions have been developed. Risk models are most useful in connection with interventions because the absolute risk of breast cancer can be compared with that of other health outcomes in the presence and absence of intervention. 3) The model is simple: only age and answers to five questions about reproductive, family, and medical history are needed. 4) The model (sometimes called the “Gail model”) has been taken up by practitioners and is available at http://www.cancer.gov/bcrisktool/ as the National Cancer Institute’s (NCI’s) Breast Cancer Risk Assessment Tool (BCRAT). Currently this site is visited over three million times a year. I shall elaborate on the first two points, mention alternative models, and discuss prospects for improving risk models and other applications of absolute risk.
ADHD Medications and Risk of Serious Cardiovascular Events in Young and Middle-aged Adults
Authors: Laurel A. Habel, William O. Cooper, Colin M. Sox, K. Arnold Chan, Bruce H. Fireman, Patrick G. Arbogast, T. Craig Cheetham, Virginia P. Quinn, Sascha Dublin, Denise M. Boudreau, Susan E. Andrade, Pamala A. Pawloski, Marsha A. Raebel, David H. Smith, Ninah Achacoso, Connie Uratsu, Alan S. Go, Steve Sidney, Mai N. Nguyen-Huynh, Wayne A. Ray, Joe V. Selby
Journal: JAMA (2011)

More than 1.5 million US adults use stimulants and other medications labeled for treatment of attention-deficit/hyperactivity disorder (ADHD). These agents can increase heart rate and blood pressure, raising concerns about their cardiovascular safety.To examine whether current use of medications prescribed primarily to treat ADHD is associated with increased risk of serious cardiovascular events in young and middle-aged adults.Retrospective, population-based cohort study using electronic health care records from 4 study sites (OptumInsight Epidemiology, Tennessee Medicaid, Kaiser Permanente California, and the HMO Research Network), starting in 1986 at 1 site and ending in 2005 at all sites, with additional covariate assessment using 2007 survey data. Participants were adults aged 25 through 64 years with dispensed prescriptions for methylphenidate, amphetamine, or atomoxetine at baseline. Each medication user (n = 150,359) was matched to 2 nonusers on study site, birth year, sex, and calendar year (443,198 total users and nonusers).Serious cardiovascular events, including myocardial infarction (MI), sudden cardiac death (SCD), or stroke, with comparison between current or new users and remote users to account for potential healthy-user bias.During 806,182 person-years of follow-up (median, 1.3 years per person), 1357 cases of MI, 296 cases of SCD, and 575 cases of stroke occurred. There were 107,322 person-years of current use (median, 0.33 years), with a crude incidence per 1000 person-years of 1.34 (95% CI, 1.14-1.57) for MI, 0.30 (95% CI, 0.20-0.42) for SCD, and 0.56 (95% CI, 0.43-0.72) for stroke. The multivariable-adjusted rate ratio (RR) of serious cardiovascular events for current use vs nonuse of ADHD medications was 0.83 (95% CI, 0.72-0.96). Among new users of ADHD medications, the adjusted RR was 0.77 (95% CI, 0.63-0.94). The adjusted RR for current use vs remote use was 1.03 (95% CI, 0.86-1.24); for new use vs remote use, the adjusted RR was 1.02 (95% CI, 0.82-1.28); the upper limit of 1.28 corresponds to an additional 0.19 events per 1000 person-years at ages 25-44 years and 0.77 events per 1000 person-years at ages 45-64 years.Among young and middle-aged adults, current or new use of ADHD medications, compared with nonuse or remote use, was not associated with an increased risk of serious cardiovascular events. Apparent protective associations likely represent healthy-user bias.
Prevention by daily soluble aspirin of colorectal adenoma recurrence: 4-year results of the APACC randomised trial
Authors: Robert Benamouzig, Bernard Uzzan, Jacques Deyra, Antoine Martin, Bernard Girard, Julian Little, Stanislas Chaussade
Journal: Gut (2011)

<h3>Background</h3> Aspirin inhibits colorectal carcinogenesis. In a randomised double-blind placebo-controlled trial, daily soluble aspirin significantly reduced recurrence of colorectal adenomas at 1-year follow-up. In this study the results of daily intake of low-dose aspirin on polyp recurrence at 4-year follow-up are presented. <h3>Methods</h3> 272 patients (naive for chronic aspirin use) with colorectal adenomas were randomly assigned to treatment with lysine acetylsalicylate 160 mg/day (n=73) or 300 mg/day (n=67) or placebo (n=132) for 4 years. The primary endpoints were adenoma recurrence and adenomatous polyp burden at year 4, comparing aspirin at either dose with placebo. The same endpoints were also assessed at year 1 or 4 (last colonoscopy performed for each patient). <h3>Results</h3> At the final year 4 colonoscopy the analysis included 185 patients (55 receiving aspirin 160 mg/day, 47 aspirin 300 mg/day and 83 placebo). There was no difference in the proportion of patients with at least one recurrent adenoma between patients receiving aspirin at either dose and those treated with placebo (42/102 (41%) vs 33/83 (40%); NS) or in the adenomatous polyp burden (3.1±5.8 mm vs 3.4±6.2 mm; NS). Also, the proportion of patients with at least one advanced recurrent adenoma did not differ (10/182 (10%) in the aspirin group vs 7/83 (7%) in the placebo group; NS). <h3>Conclusion</h3> Daily low-dose aspirin decreased adenoma recurrence significantly at 1 year but not at year 4. This discrepancy might be explained by a differential effect of aspirin according to the natural history of the polyp. <h3>Trial Registration Number</h3> NCT 00224679.