tbuckley/cabot-search huggingface dataset:
New Insights Into the Regulation of HDL Metabolism and Reverse Cholesterol Transport
Authors: Gary F. Lewis, Daniel J. Rader
Journal: Circulation Research (2005)

The metabolism of high-density lipoproteins (HDL), which are inversely related to risk of atherosclerotic cardiovascular disease, involves a complex interplay of factors regulating HDL synthesis, intravascular remodeling, and catabolism. The individual lipid and apolipoprotein components of HDL are mostly assembled after secretion, are frequently exchanged with or transferred to other lipoproteins, are actively remodeled within the plasma compartment, and are often cleared separately from one another. HDL is believed to play a key role in the process of reverse cholesterol transport (RCT), in which it promotes the efflux of excess cholesterol from peripheral tissues and returns it to the liver for biliary excretion. This review will emphasize 3 major evolving themes regarding HDL metabolism and RCT. The first theme is that HDL is a universal plasma acceptor lipoprotein for cholesterol efflux from not only peripheral tissues but also hepatocytes, which are a major source of cholesterol efflux to HDL. Furthermore, although efflux of cholesterol from macrophages represents only a tiny fraction of overall cellular cholesterol efflux, it is the most important with regard to atherosclerosis, suggesting that it be specifically termed macrophage RCT. The second theme is the critical role that intravascular remodeling of HDL by lipid transfer factors, lipases, cell surface receptors, and non-HDL lipoproteins play in determining the ultimate metabolic fate of HDL and plasma HDL-c concentrations. The third theme is the growing appreciation that insulin resistance underlies the majority of cases of low HDL-c in humans and the mechanisms by which insulin resistance influences HDL metabolism. Progress in our understanding of HDL metabolism and macrophage reverse cholesterol transport will increase the likelihood of developing novel therapies to raise plasma HDL concentrations and promote macrophage RCT and in proving that these new therapeutic interventions prevent or cause regression of atherosclerosis in humans.
Persistence of lymphoblasts in bone marrow on day 15 and days 22 to 25 of remission induction predicts a dismal treatment outcome in children with acute lymphoblastic leukemia
Authors: John T. Sandlund, Patricia L. Harrison, Gaston Rivera, Frederick G. Behm, David Head, James Boyett, Jeffrey E. Rubnitz, Amar Gajjar, Susana Raimondi, Raul Ribeiro, Melissa Hudson, Mary Relling, William Evans, Ching-Hon Pui
Journal: Blood (2002)
Hospitalization for lower respiratory disease during 20 yrs among under 5 yr old children in Stockholm County: a population based survey
Authors: M Wickman, BY Farahmand, PG Persson, G Pershagen
Journal: European Respiratory Journal (1998)

Lower respiratory disease (LRD) is a common cause of hospitalization in infants, and episodes of obstructive LRD increase the risk for asthma later in life. The purpose of this study was to assess time trends and geographical variation of first time hospitalization for LRD among children in Stockholm County, Sweden. Data on first time admittance for LRD among children aged up to 5 yrs from 1973 through 1992 were obtained from the Stockholm County Council hospital discharge register, and population register data were used for estimation of the population at risk. Municipal data were available for 1982-1992 on outbreaks of respiratory syncytial virus (RSV) infections and socio-economic factors. A total of 12,450 children had been hospitalized for the first time with LRD. For children aged <2 yrs a 100% increase in the rate of first time hospitalization for LRD was observed during the study period and children aged up to 1 yr predominated (50%). The average yearly increase in the population based first time hospital admission rate for LRD was 1.82%. Males constituted 65% of the cases. Of the diagnoses, 89.6% were consistent with obstructive LRD, e.g. asthma and obstructive bronchitis. In children aged up to 1 yr, peaks in the rate of hospitalization tended to coincide with outbreaks of RSV infections. Differences in hospitalization between municipalities seemed to be partly explained by differences in the admission practices of the four paediatric hospitals in the area. We conclude that the increased rate of hospitalization for lower respiratory disease in infants of Stockholm County may reflect a true increase in the incidence of obstructive respiratory disease. However, several factors determine admittance to hospital and the results need to be interpreted with caution.
How Do We Define Cure of Diabetes?
Authors: John B. Buse, Sonia Caprio, William T. Cefalu, Antonio Ceriello, Stefano Del Prato, Silvio E. Inzucchi, Sue McLaughlin, Gordon L. Phillips, R. Paul Robertson, Francesco Rubino, Richard Kahn, M. Sue Kirkman
Journal: Diabetes Care (2009)

The mission of the American Diabetes Association is “to prevent and cure diabetes and to improve the lives of all people affected by diabetes.” Increasingly, scientific and medical articles (1) and commentaries (2) about diabetes interventions use the terms “remission” and “cure” as possible outcomes. Several approved or experimental treatments for type 1 and type 2 diabetes (e.g., pancreas or islet transplants, immunomodulation, bariatric/metabolic surgery) are of curative intent or have been portrayed in the media as a possible cure. However, defining remission or cure of diabetes is not as straightforward as it may seem. Unlike “dichotomous” diseases such as many malignancies, diabetes is defined by hyperglycemia, which exists on a continuum and may be impacted over a short time frame by everyday treatment or events (medications, diet, activity, intercurrent illness). The distinction between successful treatment and cure is blurred in the case of diabetes. Presumably improved or normalized glycemia must be part of the definition of remission or cure. Glycemic measures below diagnostic cut points for diabetes can occur with ongoing medications (e.g., antihyperglycemic drugs, immunosuppressive medications after a transplant), major efforts at lifestyle change, a history of bariatric/metabolic surgery, or ongoing procedures (such as repeated replacements of endoluminal devices). Do we use the terms remission or cure for all patients with normal glycemic measures, regardless of how this is achieved?

A consensus group comprised of experts in pediatric and adult endocrinology, diabetes education, transplantation, metabolism, bariatric/metabolic surgery, and (for another perspective) hematology-oncology met in June 2009 to discuss these issues. The group considered a wide variety of questions, including whether it is ever accurate to say that a chronic illness is cured; what the definitions of management, remission, or cure might be; whether goals of managing comorbid conditions revert to those of patients without diabetes if someone is …
Out of the theoretical cul-de-sac
Authors: Ralph Hertwig, Annika Wallin
Journal: Behavioral and Brain Sciences (2004)

A key premise of the heuristics-and-biases program is that heuristics are “quite useful.” Let us now pay more than lip service to this premise, and analyse the environmental structures that make heuristics more or less useful. Let us also strike from the long list of biases those phenomena that are not biases and explore to what degree those that remain are adaptive or can be understood as by-products of adaptive mechanisms.
Hepatic expression of glutamine synthetase in rats is controlled by STAT5 and TCF transcription factors
Authors: Max Werth, Rolf Gebhardt, Frank Gaunitz
Journal: Hepatology (2006)

In mammalian liver, high glutamine synthetase (GS) expression is restricted to hepatocytes surrounding the terminal venules. The most important enhancer of the GS gene is located ≈2520 base pairs (bp) upstream from the transcriptional start point. The nature of the transcription factors that bind to the enhancers has remained enigmatic. In this study, we purified nuclear proteins binding to the element. Supershift assays and footprint experiments with purified protein identified activated STAT5 as a transcription factor binding to a site within the enhancer. In addition, a second binding site close to the STAT5 site was observed that also binds a protein present in nuclear extracts. Sequence analysis indicated that the second site may bind a member of the LEF/TCF transcription factor family. Reporter gene assays demonstrate that the STAT5 binding site mediates enhancement of expression whereas the LEF/TCF site functions as a silencer of growth hormone-mediated enhancement in normal hepatocytes. LEF/TCF-sites are known to function as silencers in the absence and as enhancers in the presence of activated β-catenin. In conclusion, the GS 5′ enhancer contains elements important for GS expression in cells carrying an activated form of β-catenin as previously shown in experimentally induced hepatocellular carcinomas. (HEPATOLOGY 2006;44:967–975.)
Proteasome Inhibitors Evoke Latent Tumor Suppression Programs in Pro-B MLL Leukemias through MLL-AF4
Authors: Han Liu, Todd D. Westergard, Amanda Cashen, David R. Piwnica-Worms, Lori Kunkle, Ravi Vij, Can G. Pham, John DiPersio, Emily H. Cheng, James J. Hsieh
Journal: Cancer Cell (2014)
Clomiphene, Metformin, or Both for Infertility in the Polycystic Ovary Syndrome
Authors: Richard S. Legro, Huiman X. Barnhart, William D. Schlaff, Bruce R. Carr, Michael P. Diamond, Sandra A. Carson, Michael P. Steinkampf, Christos Coutifaris, Peter G. McGovern, Nicholas A. Cataldo, Gabriella G. Gosman, John E. Nestler, Linda C. Giudice, Phyllis C. Leppert, Evan R. Myers
Journal: New England Journal of Medicine (2007)

The polycystic ovary syndrome is a common cause of infertility. Clomiphene and insulin sensitizers are used alone and in combination to induce ovulation, but it is unknown whether one approach is superior.We randomly assigned 626 infertile women with the polycystic ovary syndrome to receive clomiphene citrate plus placebo, extended-release metformin plus placebo, or a combination of metformin and clomiphene for up to 6 months. Medication was discontinued when pregnancy was confirmed, and subjects were followed until delivery.The live-birth rate was 22.5% (47 of 209 subjects) in the clomiphene group, 7.2% (15 of 208) in the metformin group, and 26.8% (56 of 209) in the combination-therapy group (P<0.001 for metformin vs. both clomiphene and combination therapy; P=0.31 for clomiphene vs. combination therapy). Among pregnancies, the rate of multiple pregnancy was 6.0% in the clomiphene group, 0% in the metformin group, and 3.1% in the combination-therapy group. The rates of first-trimester pregnancy loss did not differ significantly among the groups. However, the conception rate among subjects who ovulated was significantly lower in the metformin group (21.7%) than in either the clomiphene group (39.5%, P=0.002) or the combination-therapy group (46.0%, P<0.001). With the exception of pregnancy complications, adverse-event rates were similar in all groups, though gastrointestinal side effects were more frequent, and vasomotor and ovulatory symptoms less frequent, in the metformin group than in the clomiphene group.Clomiphene is superior to metformin in achieving live birth in infertile women with the polycystic ovary syndrome, although multiple birth is a complication. (ClinicalTrials.gov number, NCT00068861 [ClinicalTrials.gov].).
Diabetes and Abnormal Glucose Tolerance in Women With Previous Gestational Diabetes
Authors: Mercè Albareda, Agueda Caballero, Gemma Badell, Sandra Piquer, Angels Ortiz, Alberto de Leiva, Rosa Corcoy
Journal: Diabetes Care (2003)

OBJECTIVE—In Spanish women with gestational diabetes mellitus (GDM), we aimed to study the progression to diabetes and abnormal glucose tolerance (AGT) and identify predictive factors. RESEARCH DESIGN AND METHODS—In 696 women with GDM and 70 control women, glucose tolerance was evaluated postpartum and at 5-year intervals. RESULTS—In the GDM group, the cumulative risk for diabetes and AGT was 13.8 and 42.4% after 11 years compared with 0 and 2.8% in control women, respectively (P &amp;lt; 0.05). Independent predictive factors for diabetes were previous hyperglycemia, four abnormal glucose values on the diagnostic oral glucose tolerance test (OGTT) or overt diabetes during pregnancy, 2-h blood glucose on the diagnostic OGTT ≥11.7 mmol/l, gestational age at diagnosis &amp;lt;24 weeks, and prepregnancy BMI ≥26.4 kg/m2. All of these factors (some with different cutoff points) in addition to fasting glycemia were predictors of AGT also. The risk was nonlinear. Four abnormal glucose values on the diagnostic OGTT or overt diabetes during pregnancy was the strongest predictive factor for diabetes (relative risk 3.92), and prepregnancy BMI was the predictive factor with the highest attributable fraction in the whole group (13.3%). When first postpartum OGTT data were included in the analysis, predictors changed, but the overall prediction was similar. CONCLUSIONS—Spanish women with GDM have an increased risk of diabetes and AGT. Predictive factors display a nonlinear relationship. The strongest predictive factor for diabetes was four abnormal glucose values on the diagnostic OGTT or overt diabetes during pregnancy; the factor with the highest attributable fraction in the whole group was prepregnancy BMI.
Sequence-Function Relationships Within the Expanding Family of Prolactin, Growth Hormone, Placental Lactogen, and Related Proteins in Mammals*
Authors: VINCENT GOFFIN, KATHLEEN T. SHIVERICK, PAUL A. KELLY, JOSEPH A. MARTIAL
Journal: Endocrine Reviews (1996)

I. Introduction PRL PL, and GH are homologous proteins that are thought to have arisen from a common ancestral gene by two successive tandem duplications (Refs. 1–5; for review, see Ref. 6). PRL and GH are mainly secreted by the anterior pituitary of all vertebrates. The divergence of the PRL and GH lineage from the common ancestral gene has been located some 400 million years ago, which is in good agreement with the presence of distinct PRL and GH in fish (2, 3, 6, 7). PL is uniquely observed in mammals and is secreted in the placenta by syncytiotrophoblastic cells (for reviews, see Refs. 8–10). Initially, PLs were proposed to have evolved from the common PRL/GH precursor gene (1). Further cloning and analysis of PRL, GH, and PL genes from different species (chromosome carrier, gene size, splicing sites, sequence identity; see Refs. 6, 7, 11, and 12) have led to a reconsideration of this hypothesis, and it is now assumed that primate PLs evolved from the GH lineage while nonprimate PLs arose from the PRL...
A Randomized Trial of Low-Dose Aspirin in the Primary Prevention of Cardiovascular Disease in Women
Authors: Paul M Ridker, Nancy R. Cook, I-Min Lee, David Gordon, J. Michael Gaziano, JoAnn E. Manson, Charles H. Hennekens, Julie E. Buring
Journal: New England Journal of Medicine (2005)

Randomized trials have shown that low-dose aspirin decreases the risk of a first myocardial infarction in men, with little effect on the risk of ischemic stroke. There are few similar data in women.We randomly assigned 39,876 initially healthy women 45 years of age or older to receive 100 mg of aspirin on alternate days or placebo and then monitored them for 10 years for a first major cardiovascular event (i.e., nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes).During follow-up, 477 major cardiovascular events were confirmed in the aspirin group, as compared with 522 in the placebo group, for a nonsignificant reduction in risk with aspirin of 9 percent (relative risk, 0.91; 95 percent confidence interval, 0.80 to 1.03; P=0.13). With regard to individual end points, there was a 17 percent reduction in the risk of stroke in the aspirin group, as compared with the placebo group (relative risk, 0.83; 95 percent confidence interval, 0.69 to 0.99; P=0.04), owing to a 24 percent reduction in the risk of ischemic stroke (relative risk, 0.76; 95 percent confidence interval, 0.63 to 0.93; P=0.009) and a nonsignificant increase in the risk of hemorrhagic stroke (relative risk, 1.24; 95 percent confidence interval, 0.82 to 1.87; P=0.31). As compared with placebo, aspirin had no significant effect on the risk of fatal or nonfatal myocardial infarction (relative risk, 1.02; 95 percent confidence interval, 0.84 to 1.25; P=0.83) or death from cardiovascular causes (relative risk, 0.95; 95 percent confidence interval, 0.74 to 1.22; P=0.68). Gastrointestinal bleeding requiring transfusion was more frequent in the aspirin group than in the placebo group (relative risk, 1.40; 95 percent confidence interval, 1.07 to 1.83; P=0.02). Subgroup analyses showed that aspirin significantly reduced the risk of major cardiovascular events, ischemic stroke, and myocardial infarction among women 65 years of age or older.In this large, primary-prevention trial among women, aspirin lowered the risk of stroke without affecting the risk of myocardial infarction or death from cardiovascular causes, leading to a nonsignificant finding with respect to the primary end point.
Faecal mucinase activity assessed in inflammatory bowel disease using 14C threonine labelled mucin substrate.
Authors: A D Dwarakanath, B J Campbell, H H Tsai, D Sunderland, C A Hart, J M Rhodes
Journal: Gut (1995)

Previous studies have shown the presence in faeces of sulphatases, sialidases, glycosidases, and proteases relevant to mucus degradation, but the relative role of these enzymes in the degradation of colonic mucus has been unclear. A total mucinase assay using 14C threonine biologically labelled human colonic mucin as substrate was therefore developed in this study. Faecal mucinase activity of a pooled normal faecal filtrate was capable of removing 80% of the 14C threonine label from mucin within eight hours incubation, but 20% remained intact despite prolonged incubation. The pH profile of mucinase activity is broad (pH 4.5-9.5) suggesting contribution from multiple enzymes. Mucinase activity was reduced by preincubation with 100 micrograms/ml chymostatin (82.8%), 0.5 mg/ml EDTA (91.6%), and 4 g/l bismuth subsalicylate (72.0%). All 55 faecal samples studied contained detectable mucinase activity, measured as dpm release/micrograms protein/hour, which was greater in samples from patients with ulcerative colitis (n = 17, median 52.7, interquartile range 32.9-66.9), than controls (n = 26, 34.4, 26.8-40.4, p &lt; 0.02) or patients with Crohn9s disease (n = 12, 35.5, 17.5-55.7, p &lt; 0.05). There was, however, no significant difference in faecal mucinase activity between inactive and active ulcerative colitis. These results suggest that faecal mucinase activity is one factor contributing to the thin mucus layer in ulcerative colitis and represents a potential target for drug treatment.
Benefits and Risks of Solitary Islet Transplantation for Type 1 Diabetes Using Steroid-Sparing Immunosuppression
Authors: Boaz Hirshberg, Kristina I. Rother, Benigno J. Digon, David M. Harlan
Journal: Diabetes Care (2004)

The results of the 5th and final year, Fiscal Year 2003, are included in Table 1.We obviously did not come close to realizing this ambitious goal.In my 1998 Presidential Address, I compared the ADA to a large ship in which a new course first required a change of direction (which would occur slowly) before proceeding toward and hopefully reaching a new port.It's obvious that we have not reached that port, and realistically speaking, we probably never will.However, I would be remiss if I didn't point out the following.In each of the previous years, the increase in funding for Research Awards and Grants was much less than
Genetics and pulmonary medicine bullet 9: Molecular genetics of chronic obstructive pulmonary disease
Authors: P. J Barnes
Journal: Thorax (1999)

Chronic obstructive pulmonary disease (COPD) is a major cause of ill health and is increasing in many parts of the world. It is one of the commonest causes of death and the only common cause of death which is increasing. COPD is characterised by a slowly progressive irreversible airflow obstruction that is due to a loss of lung elasticity resulting from parenchymal destruction and peripheral airflow obstruction. Cigarette smoking is currently a causal factor in more than 90% of patients in westernised societies, so environmental factors are clearly very important in the disease.1However, in Caucasians only 10–20% of chronic heavy cigarette smokers develop symptomatic COPD, suggesting that genetic factors are likely to be important in determining which cigarette smokers are at risk from developing airflow obstruction. Furthermore, some patients develop airflow obstruction at an earlier age, again suggesting that genetic factors may determine the progression of COPD. Patients who have a genetic deficiency in the anti-protease α1-antitrypsin (α1-AT) have a very high risk of developing emphysema at an early age if they smoke, indicating the importance of genetic factors in some patients with COPD. Despite the clinical importance of COPD, relatively few studies have searched for genetic factors using modern molecular genetic techniques.

There may also be differences in the prevalence of COPD in different ethnic groups, but these are difficult to separate from lifestyle factors. For example, the prevalence of COPD is apparently low in China and this cannot be entirely accounted for by a lower tobacco consumption.2 Anecdotally, COPD is uncommon in Chinese living in the USA which suggests that there may be genetic differences in the factors that protect against COPD. In Hawaii, the prevalence of COPD in Japanese-Americans smoking more than 20 cigarettes daily was 7.9% compared with 16.7% …