tbuckley/cabot-search huggingface dataset:
Molecular Pathways: Leveraging the BCL-2 Interactome to Kill Cancer Cells—Mitochondrial Outer Membrane Permeabilization and Beyond
Authors: Hetal Brahmbhatt, Sina Oppermann, Elizabeth J. Osterlund, Brian Leber, David W. Andrews
Journal: Clinical Cancer Research (2015)

The inhibition of apoptosis enables the survival and proliferation of tumors and contributes to resistance to conventional chemotherapy agents and is therefore a very promising avenue for the development of new agents that will enhance current cancer therapies. The BCL-2 family proteins orchestrate apoptosis at the mitochondria and endoplasmic reticulum and are involved in other processes such as autophagy and unfolded protein response (UPR) that lead to different types of cell death. Over the past decade, significant efforts have been made to restore apoptosis using small molecules that modulate the activity of BCL-2 family proteins. The small molecule ABT-199, which antagonizes the activity of BCL-2, is currently the furthest in clinical trials and shows promising activity in many lymphoid malignancies as a single agent and in combination with conventional chemotherapy agents. Here, we discuss strategies to improve the specificity of pharmacologically modulating various antiapoptotic BCL-2 family proteins, review additional BCL-2 family protein interactions that can be exploited for the improvement of conventional anticancer therapies, and highlight important points of consideration for assessing the activity of small-molecule BCL-2 family protein modulators.
Blood glucose concentrations and progression of diabetic retinopathy: the seven year results of the Oslo study.
Authors: O. Brinchmann-Hansen, K. Dahl-Jorgensen, L. Sandvik, K. F. Hanssen
Journal: BMJ (1992)

To study insulin dependent diabetic patients for change in non-proliferative retinopathy and its relation to glycaemic control and to various clinical background data.Prospective study with follow up for seven years.Outpatient departments of university hospitals.Glycated haemoglobin concentration; degree of retinopathy.Retinopathy worsened by an overall increase in counts of microaneurysms and haemorrhages from 17 (SD 25) to 45 (58) (p = 0.005). Intensified insulin treatment and home blood glucose monitoring improved concentrations of glycated haemoglobin (HbA1) from 11.2% (2.2%) at the start of the study to a mean of 9.5% (1.5%) over the seven years of the study (p less than 0.0001). A mean value for HbA1 greater than 10% was associated with an increased risk of progression of retinopathy and a mean value less than 8.7% was associated with a diminished risk. Multiple regression analysis identified four independent variables as indicative of outcome of retinopathy after seven years: HbA1 value at baseline; the change in HbA1 from start to the mean level through the seven years; duration of diabetes; and retinopathy at start. Age, blood pressure, and urinary albumin excretion were not related to the presence or progression of retinopathy.Secondary intervention by long term lowering of glycated haemoglobin has a beneficial impact on non-proliferative retinopathy. A four factor regression model can determine patients at high risk of severe retinopathy.
Insulin-like Growth Factor Messenger RNA-binding Protein 3 Expression Helps Prognostication in Patients with Upper Tract Urothelial Carcinoma
Authors: Daniel J. Lee, Evanguelos Xylinas, Malte Rieken, Francesca Khani, Tobias Klatte, Christopher G. Wood, Jose A. Karam, Alon Z. Weizer, Jay D. Raman, Mesut Remzi, Charles C. Guo, Nathalie Rioux-Leclercq, Andrea Haitel, Christian Bolenz, Karim Bensalah, Arthur I. Sagalowsky, Francesco Montorsi, Yair Lotan, Shahrokh F. Shariat, Brian D. Robinson, Vitaly Margulis
Journal: European Urology (2013)
Subjects with allergic reactions to drugs show in vivo polarized patterns of cytokine expression depending on the chronology of the clinical reaction
Authors: Sinforiano J. Posadas, Laura Leyva, Maria J. Torres, Jose L. Rodriguez, Immaculada Bravo, Manuel Rosal, Javier Fernandez, Carlos Juarez, Miguel Blanca
Journal: Journal of Allergy and Clinical Immunology (2000)
Management of pregnancies with RhD alloimmunisation
Authors: Sailesh Kumar, Fiona Regan
Journal: BMJ (2005)

Pregnancies complicated by red cell alloimmunisation may result in fetal anaemia secondary to transplacental passage of maternal immunoglobulin G, which causes progressive fetal haemolysis.In severe cases the anaemic fetus develops ascites, subcutaneous oedema, and pleural and pericardial effusions (hydrops fetalis) and dies in the womb.Many different antibodies (anti-D, anti-Kell, anti-c, anti-E, etc) can cause haemolytic disease of the fetus and newborn.This review covers the management of pregnancies affected with RhD alloimmunisation.The principles of management are similar regardless of the type of antibody involved, although care needs to be taken with pregnancies complicated by Kell alloimmunisation, where antibody concentrations do not always correlate with disease severity.We searched PubMed for up to date references on current advances in the treatment of RhD alloimmunisation.In addition, we used guidelines on antenatal care and prophylaxis from the websites of the National Institute for Clinical Excellence (NICE, www.nice.org.uk) and the Royal College of Obstetricians and Gynaecologists (www.rcog.org.uk).Hydrops fetalis was first described in 1609 by a French midwife, Louise Borgeois, 1 after the birth of twins one of whom was oedematous and the other deeply jaundiced; both died soon after the birth.However, it was not until 1940 that Landsteiner and Weiner, using rhesus monkeys, discovered the RhD antigen. 2
Obstructive Jaundice Due to Bullet in Hepatic Duct
Authors: Emmett L. Hebert, Jerome M. Swarts
Journal: New England Journal of Medicine (1954)

THE presence of a foreign body in the extrahepatic biliary tract is extremely infrequent judging from the paucity of reports in the medical literature.1 2 3 4 5 6 7 8 9 10 11 Having recently been confronted by the problem of obstructive jaundice developing several years after a wound, we believe that the case, together with its diagnostic and pathogenetic aspects, merits reporting. Previously reported cases are presented in Table 1.Case ReportJ.D., a 29-year-old man, was admitted to the hospital on December 2, 1953. During combat activity in 1944 he received several gunshot wounds of the right lateral and posterior aspects of the chest. Surgical operation was performed . . .
Smoking, obesity, and their co-occurrence in the United States: cross sectional analysis
Authors: Cheryl G Healton, Donna Vallone, Kristen L McCausland, Haijun Xiao, Molly P Green
Journal: BMJ (2006)

<h3>Abstract</h3> <b>Objectives</b> To describe the prevalence of obesity, smoking, and both health risk factors together among adults in the United States. <b>Design</b> Cross sectional analysis of a national health interview survey. <b>Setting</b> United States. <b>Participants</b> 29 305 adults (aged ≥ 18) in 2002. <b>Main outcome measures</b> Prevalence of adults who are obese (body mass index ≥ 30), who smoke, and who are obese and smoke. Prevalence was stratified by age, sex, ethnic group, education, and income. <b>Results</b> 23.5% of adults were obese, 22.7% smoked, and 4.7% smoked and were obese. <b>Conclusions</b> Although the proportion of adults who smoke and are obese is relatively low, this subgroup is concentrated among lower socioeconomic groups.
Dual gas techniques for peripheral airway function: diffusing the issues
Authors: Sylvia Verbanck, Manuel Paiva
Journal: European Respiratory Journal (2015)

In the quest to investigate small airway function in a range of lung diseases, multiple-breath washout tests have been applied for their potential to represent the most peripheral air spaces [1, 2]. The aim of reducing the burden on the patient has recently also revived interest in the single-breath washout. A single-breath washout test has now been proposed which involves an inhalation of 5% SF6, 26.3% He, 21% O2 and the balance as N2 in order to obtain a so-called dual gas tracer (DTG) phase III slope [3]. After having been introduced as a practical and promising lung function tool [3] and as an early detection tool in cystic fibrosis lung disease [4], the DTG phase III slope is now advocated as a specific index of acinar function abnormality in children with mild asthma [5]. An editorial in the European Respiratory Journal [6], reflecting upon a DTG reproducibility study in normal subjects and chronic obstructive pulmonary disease (COPD) patients [7], rightly pointed out that the clinical utility of DTG indices will depend on their actual physiological meaning. We provide here a critical appraisal of the physiological meaning of the DTG phase III slope. Peripheral ventilation heterogeneity can be extracted from the dual gas test by considering all its gas components <http://ow.ly/I62C8>
Abstract 1017: Phosphorylation of histone H2AX at Ser139 and a new phosphorylation site Ser16 by RSK2 decreases H2AX ubiquitination and inhibits cell transformation
Authors: Feng Zhu, Tatyana Zykova, Cong Peng, Jishuai Zhang, Yong-Yeon Cho, Duo Zheng, Ke Yao, Wei-Ya Ma, Andy T.Y. Lau, Ann M. Bode, Zigang Dong
Journal: Cancer Research (2011)

Abstract Histone H2AX is a histone H2A variant that is ubiquitously expressed throughout the genome. It plays a key role in the cellular response to DNA damage and has been designated as the histone guardian of the genome. H2AX deficiency decreases genomic stability and increases tumor susceptibility of normal cells and tissues. However, the role of H2AX phosphorylation in malignant transformation and cancer development is not totally clear. We found that ribosomal S6 kinase 2 (RSK2) directly phosphorylates H2AX at Ser139 and also at a newly discovered site, Ser16. EGF-induced phosphorylation of H2AX at both sites was decreased in RSK2 knockout cells. Phosphorylated RSK2 and H2AX co-localized in the nucleus following EGF treatment and the phosphorylation of H2AX by RSK2 enhanced the stability of H2AX and prevented cell transformation induced by EGF. RSK2 and DNA-PK, but not ATM or ATR, are required for EGF-induced phosphorylation of H2AX at Ser139. However, only RSK2 is required for phosphorylation of H2AX at Ser16. Phosphorylation of histone H3 was suppressed in cells expressing wildtype H2AX compared with H2AX knockout (H2AX-/-) cells. EGF-associated AP-1 transactivation activity was dramatically lower in H2AX-/- cells overexpressing wildtype H2AX compared with H2AX-/- cells expressing mutant H2AX-AA. Thus, the RSK2/H2AX signaling pathway negatively regulates the RSK2/histone H3 pathway and therefore maintains normal cell proliferation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1017. doi:10.1158/1538-7445.AM2011-1017
Problems in the Diagnosis and Surgical Treatment of Pulmonic Stenosis with Intact Ventricular Septum
Authors: JOHN W. KIRKLIN, DANIEL C. CONNOLLY, F. HENRY ELLIS, HOWARD B. BURCHELL, JESSE E. EDWARDS, EARL H. WOOD
Journal: Circulation (1953)

Obstruction to pulmonary blood flow may occur in the pulmonic valve, in the infundibulum or in both. Cardiac catheterization aids in the determination of the site of obstruction. Criteria for the differentiation at operation of valvular and infundibular pulmonic stenosis are enumerated, and the usefulness of accurate pressure tracings during operation is emphasized. The accurate identification of the site or sites of obstruction to pulmonary blood flow is essential to proper surgical management. A correctly selected operation must be carried out in as complete a manner as possible.
A Prospective Study of Red Meat Consumption and Type 2 Diabetes in Middle-Aged and Elderly Women
Authors: Yiqing Song, JoAnn E. Manson, Julie E. Buring, Simin Liu
Journal: Diabetes Care (2004)

OBJECTIVE—The aim of this study was to prospectively assess the relation between red meat intake and incidence of type 2 diabetes. RESEARCH DESIGN AND METHODS—Over an average of 8.8 years, we evaluated 37,309 participants in the Women’s Health Study aged ≥45 years who were free of cardiovascular disease, cancer, and type 2 diabetes and completed validated semiquantitative food frequency questionnaires in 1993. RESULTS—During 326,876 person-years of follow-up, we documented 1,558 incident cases of type 2 diabetes. After adjusting for age, BMI, total energy intake, exercise, alcohol intake, cigarette smoking, and family history of diabetes, we found positive associations between intakes of red meat and processed meat and risk of type 2 diabetes. Comparing women in the highest quintile with those in the lowest quintile, the multivariate-adjusted relative risks (RRs) of type 2 diabetes were 1.28 for red meat (95% CI 1.07–1.53, P &amp;lt; 0.001 for trend) and 1.23 for processed meat intake (1.05–1.45, P = 0.001 for trend). Furthermore, the significantly increased diabetes risk appeared to be most pronounced for frequent consumption of total processed meat (RR 1.43, 95% CI 1.17–1.75 for ≥5/week vs. &amp;lt;1/month, P &amp;lt; 0.001 for trend) and two major subtypes, which were bacon (1.21, 1.06–1.39 for ≥2/week vs. &amp;lt;1/week, P = 0.004 for trend) and hot dogs (1.28, 1.09–1.50 for ≥2/week vs. &amp;lt;1/week, P = 0.003 for trend). These results remained significant after further adjustment for intakes of dietary fiber, magnesium, glycemic load, and total fat. Intakes of total cholesterol, animal protein, and heme iron were also significantly associated with a higher risk of type 2 diabetes. CONCLUSIONS—Our data indicate that higher consumption of total red meat, especially various processed meats, may increase risk of developing type 2 diabetes in women.
Decreased iron burden in overweight C282Y homozygous women: Putative role of increased hepcidin production
Authors: Romain Desgrippes, Fabrice Lainé, Jeff Morcet, Michèle Perrin, Ghislain Manet, Caroline Jezequel, Edouard Bardou-Jacquet, Martine Ropert, Yves Deugnier
Journal: Hepatology (2013)

An excess of visceral adipose tissue could be involved as a modulator of the penetrance of HFE hemochromatosis since fat mass is associated with overexpression of hepcidin and low transferrin saturation was found to be associated with being overweight in women. This study was aimed at assessing the relationship between body mass index (BMI), a surrogate marker of insulin resistance, and iron burden in HFE hemochromatosis. In all, 877 patients from a cohort of C282Y homozygotes were included in the study when BMI at diagnosis and amount of iron removed (AIR) by phlebotomy were available. No relationship between AIR and BMI was found in men, whereas 15.1% (52/345) of women with AIR <6 g had BMI ≥28 versus 3.9% (2/51) of women with AIR ≥6 g (P = 0.03). At multivariate analysis, BMI was an independent factor negatively associated with AIR (odds ratio: 0.13; 95% confidence interval [CI]: 0.03-0.71) together with serum ferritin, serum transferrin, transferrin saturation, hemoglobin, and alanine aminotransferase. In a control group of 30 C282Y homozygous women, serum hepcidin was significantly higher in overweight (14.3 mmoL/L ± 7.1) than in lean (7.9 mmoL/L ± 4.3) women (P = 0.0005).In C282Y homozygous women, BMI ≥28 kg/m(2) is independently associated with a lower amount of iron removed by phlebotomy. BMI is likely a modulator factor of the phenotypic expression of C282Y homozygosity, likely through an increase of circulating levels of hepcidin.
Surgery of the Gastrointestinal Tract
Authors: Claude E. Welch
Journal: JAMA (1974)

This book is a compilation of papers presented at a recent postgraduate course at the University of Minnesota. The editors succeeded in their determination to extract statements from nearly all of their participants— no small feat itself—and have enlivened the text by terse abstracts of discussions. As a result, the reader believes he actually is sitting in the auditorium listening to the drop of pearl after pearl as distinguished visiting professors, reinforced by local faculty, speak on their favorite topics. The impression is strengthened by numerous illustrations, some of which are excellent, and some of which appear to be slides, seen hazily from the rear of the room. References, by the same token, are generally very brief or absent. It is difficult to single out any special sections for commendation, for the entire text is stimulating. Suffice it to say that many controversial subjects are considered as well as the
The Kimbanguist Hospital at Kinshasa, Zaire.
Authors: Z Stern, E Mor
Journal: BMJ (1990)

BrMedJ 1990;301:1437-8 In the early 1980s the Kimbanguist Church in Zaire decided to establish a hospital in the Kimbanseke area of Kinshasa, the capital. Kimbanseke is one of the largest and most impoverished areas of Kinshasa, with a population of about 350 000 and an annual population growth rate of 3%. Although subject to rapid urbanisa? tion, the district has inadequate water supplies and sewage facilities, and until the hospital was built Kimbanseke was served by only a few dispersed clinics. The Kimbanguist Church is a Catholic church established in the 1960s by Priest Simone Kimbange. It has about four million worshippers in Zaire (out of a total population of about 35 million) and another
Avoiding Unnecessary Duplication Of Medical Services
Authors: Basil R. Meyerowitz
Journal: JAMA (1972)

<h3>To the Editor.—</h3> To mention the British National Health Service in contemporary America is tantamount to waving a red flag to an enraged bull, and I have no intention of so doing. Nonetheless, there are some features of that system which could be applied almost immediately to the American health-care scene with distinct advantage. One of these stands out as eminently sensible and fiscally sound; every patient in Britain is required to "contract" with a primary physician of his choosing. In Britain, there appears to be a fairly large number of general practitioners who fulfill this role. In this country, primary physicians often are general practitioners as well as internists, pediatricians, and sometimes even general surgeons and gynecologists. They could certainly function as primary physicians in this context if they wished. The physician, approached by a patient, may decline to take the patient because his work load is already too
Digital Social Networks and Health
Authors: R. Craig Lefebvre, Alexandra S. Bornkessel
Journal: Circulation (2013)

T his article documents the emergence of social media, and specifically social network sites (SNS) and their impact on health information-seeking and health-related behaviors.We review surveys of user behavior on SNS to document how health information is being transformed into a social health experience rather than an individual or clinical endeavor.We then turn to the research evidence for how SNS may influence health behaviors.Although there is a substantial literature that provides support for the role of social variables in the genesis and management of health and disease, there is little scientific grounding for how to leverage these variables to improve health in either online or offline milieus.We conclude with recommendations for practice to optimize the use of social media and its contribution to improved health outcomes, and pose a series of questions that may guide the development of a research agenda in this area.The technological innovations of blogs, podcasts, interactive media, and SNS have enabled many people to create, post, and share their own messages and content by using a variety of digital social communication tools and platforms.People and organizations can now quickly create and deliver content through more interactive Web sites and online communities where, for example, people with medical conditions can seek, give, and receive advice from other patients and healthcare providers. 1,2New communication technologies and the emergence of what has been dubbed Web 2.0 are providing the opportunity for health professionals and patients alike to engage with 1 another, their peers, friends, and families in ways unimaginable just a few years ago.The speed and scale of adoption of social media is changing the way we think about and communicate with people formerly known as audiences and the way doctors and patients interact, 2,3 bringing about a new social health experience.Yet, these social media and interactive elements have been poorly integrated into many health-related Web sites, for example, those dedicated to tobacco control. 4n its simplest forms, these media can be thought of as digital extensions of the interpersonal channels of connection and the narrowing of broadcast-type communication.They are increasing access to, connection with, and discussions of health information.The information is no longer static, but alive and moving-weaving through networks of individuals and communities whether on-or offline. 3Thinking about these new media as just new communication channels misses the essence of what the new revolution is all about: using media in new ways.In this article, we review how people are using the Internet, social media, and specifically SNS in health and medicine to create a new social health experience.
Our Lights Are on for Safety
Authors: Paul S. Pottinger
Journal: JAMA Internal Medicine (2013)

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Pharmaceutical Formulation and Therapeutic Efficacy
Authors: Gerhard Levy
Journal: JAMA (1961)

Formulation of drugs into various dosage forms may modify profoundly the onset, intensity, and duration of physiological response, the correct dosage for the patient, the incidence and intensity of side effects, and the stability of the drugs. These effects are illustrated by examples from the clinical and scientific literature. Because of the modifications discussed, it is clear that in some cases choice of dosage form and manufacturer's brand may be as important as choice of the actual therapeutic agent.