tbuckley/cabot-search huggingface dataset:
The impact of metabolic syndrome on insulin sensitivity, glucose sensitivity, and acute insulin response after glucose load in early-onset type 2 diabetes mellitus: Taiwan Early-Onset Type 2 Diabetes Cohort Study
Authors: Chang-Hsun Hsieh, Chung-Ze Wu, Fone-Ching Hsiao, Jiunn-Diann Lin, Jer-Chuan Li, Hsiang-Lin Wan, Shi-Wen Kuo, Yi-Jen Hung, Ching-Chieh Su, Dee Pei
Journal: Metabolism (2008)
Toll-like Receptor-mediated Tumor Necrosis Factor and Interleukin-10 Production Differ during Systemic Inflammation
Authors: Minou Adib-Conquy, Pierre Moine, Karim Asehnoune, Alain Edouard, Terje Espevik, Kensuke Miyake, Catherine Werts, Jean-Marc Cavaillon
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Major trauma is associated with a decreased capacity of patients' leukocytes to produce proinflammatory cytokines on in vitro stimulation. We studied leukocytes from 48 patients with trauma and showed that this hyporeactivity was restricted to gram-negative bacteria, Escherichia coli endotoxin, and unmethylated bacterial DNA, whereas Leptospira interrogans endotoxin-induced tumor necrosis factor production was similar to that observed with healthy donors. As well, tumor necrosis factor and interleukin-6 production in response to gram-positive bacteria was not altered. The expression of toll-like receptor (TLR) 2 was not reduced on patients' monocytes as compared with healthy control subjects, whereas that of TLR4 was reduced. However, the hyporeactivity to gram-negative bacteria and E. coli endotoxin cannot be fully explained by the downregulation of TLR4. Indeed, unlike proinflammatory cytokines, after stimulation with these microbial products the release of antiinflammatory cytokines was increased as compared with healthy control subjects. The increased interleukin-10 production was analyzed in terms of intracellular signaling in peripheral blood mononuclear cells from patients with trauma: our results suggest the involvement of p38 mitogen-activated protein kinase, Sp-1 transcription factor, heterotrimeric Gi protein, and phosphatidylinositol-3′-kinase. In conclusion, the immunodysregulation described for patients with trauma is not a generalized phenomenon but depends on the stimulus and the signaling pathway.
Metabolism of apoprotein B of plasma very low density lipoproteins in the rat.
Authors: O Faergeman, T Sata, J P Kane, R J Havel
Journal: Journal of Clinical Investigation (1975)

As an extension of metabolic studies of the cholesteryl ester component of rat very low density lipoproteins, we have studied the metabolism of the B apoprotein component labeled by intravenous injection of [3H]lysine. The B apoprotein separated from other apoproteins by delipidation and selective precipitation with tetramethylurea could not be distinguished from B apoprotein prepared by the conventional gel filtration technique. After injection of [3H]lysine, specific activity of B apoprotein was maximal in very low density and low density lipoproteins 1 and 11/2-h later, respectively, in a manner consistent with a precursor-product relationship. When protein-labeled very low density lipoproteins were injected into rats, the relationships of specific activity again indicated that B apoprotein of very low density lipoproteins may be the sole precursor of that of low density lipoproteins. However, less than 10% of the B apoprotein that disappeared from very low density lipoproteins appeared in density lipoproteins. To evaluate the sites of removal of B aproprotein of very low density lipoproteins from plasma, protein-labeled very low density lipoproteins were incubated with unlabeled high density lipoproteins to reduce radioactivity in non-B apoproteins selectively by molecular exchange. Most of the B apoprotein was rapidly removed by the liver. The extensive hepatic uptake of both the cholesteryl ester and B apoprotein components of rat very low density lipoproteins may explain the characteristically low concentrations of plasma low density lipoproteins in the rat.
High mental disorder rates are based on invalid measures: Questions about the claimed ubiquity of mutation-induced dysfunction
Authors: Jerome C. Wakefield
Journal: Behavioral and Brain Sciences (2006)

Three reservations about Keller &amp; Miller's (K&amp;M's) argument are explored: Serious validity problems afflict epidemiological criteria discriminating disorders from non-disorders, so high rates may be misleading. Normal variation need not be mild disorder, contrary to a possible interpretation of K&amp;M's article. And, rather than mutation-selection balance, true disorders may result from unselected combinations of normal variants over many loci.
Use of Animals in Medical Education
Authors: Marjorie Cramer
Journal: JAMA (1991)

<h3>To the Editor.</h3> — I am writing in response to the Council on Scientific Affairs' "Use of Animals in Medical Education" article.<sup>1</sup>The authors would have us believe that the only people opposed to the use of animals in medical education are those who break into laboratories, deface them with graffiti, and deal out death threats. Not so: thousands of physicians, many of them AMA members, are opposed to such use. I recall from my medical school days watching a guinea pig, strategically placed on the professor's desk, die from anaphylactic shock when challenged with an allergen. It is hard to imagine that I could not have learned this equally well by reading about it or watching a computer simulation. I tried to learn about the use of epinephrine on cat muscle while repressing my horror at watching a live cat used in the demonstration. I have often thought
Annual Deaths Attributable to Obesity in the United States
Authors: David B. Allison
Journal: JAMA (1999)

BESITY IS A SERIOUS MEDIcal problem, increasing in prevalence, affecting millions, 1 and of great interest to the public.To articulate the burden of obesity, investigators have used indicators such as prevalence, 1,2 economic cost, 3 and association with risk factors and diseases. 4However, there is little published scientific information on the number of annual obesityattributable deaths in the United States.Mass media, 5-8 scholarly journals, 9-11 and pharmaceutical handouts 12 have cited 300 000 deaths per year in the United States as being attributable to obesity, a number that may have been adapted from an analysis of precursors of premature death in the United States for 1980, 13 attributing 289 502 deaths to "overnutrition."McGinnis and Foege 14 estimated that, of US deaths in 1990, 309 000 to 582 000 were associated with unhealthy diet and exercise patterns.However, neither study estimated deaths attributed specifically to obesity.We report a detailed analysis aimed at calculating the annual number of deaths attributable to obesity.It is important to clarify the quantity we are trying to estimate.If we choose a particular year, ie, 1991, we can say, "Of the people who were alive at the beginning of 1991, how many fewer would have died by the end of that year if all of the obese people alive at the beginning of the year had not been obese and if those people had the hazard of those with a BMI [body mass index] just below the cutoff for obesity (eg, BMI 23-25 kg/m 2 )."For simplicity, we refer to this quantity as "the annual number of deaths attributable to obesity." METHODSThe year 1991 was chosen for analysis because of the availability of population (1990 US census 15 ) and mortality statistics. 16Also, it was the midpoint of data collection for the Third National
Dangers of Oxytocin-induced Labour to Fetuses
Authors: M. Dixon
Journal: BMJ (1974)

45scores.The difference in the frequency of low Apg-ar scores between the two groups was not significant (X2 = 0 71; P < 0 50), nor was there any clear association in this series between low Apgar scores and the mode of delivery.Though it is appreciated that a compaTrison may not be made between in- duced and spontaneous labouLrs, it is note- worthy that in a similar series of 533 spontaneous labours studied prospectively 36 (7%,h) of the neonates had low Apgar scores, a freauency which does not differ significantly from that following induced labour.While I do not claim that oxytocin is innocuous, there seems no reason to believe on present evidence that in tihe absence of hyperton,us its use increases the risk of fetal hypoxia.
Treatment Strategies for Prostate Cancer-Reply
Authors: Craig Fleming
Journal: JAMA (1993)

<h3>In Reply.</h3> —The respondents seem to share the conviction that earlier detection and treatment of prostate cancer will reduce mortality. Unfortunately, this view is not supported by available data. Screening will undoubtedly detect tumors too small to be detected by other means. Inevitably, this process leads to apparent improvements in survival from the time of diagnosis that have nothing to do with therapeutic interventions and their effectiveness.<sup>1</sup> Drs Catalona and Switzer miss the main point of our article. We did not intend to prove that watchful waiting was more effective than invasive treatment, nor did we assume that radiation was better than surgery. We built a decision model with optimistic assumptions, biased in favor of invasive treatments, to evaluate whether either treatment might result in better outcomes than watchful waiting. We framed our article to ask a question: From the patient's point of view, is the potential for benefit
HISTOPATHOLOGY OF A FOCAL BRAIN SOFTENING
Authors: H. Douglas Singer
Journal: American Journal of Psychiatry (1924)

In this case the changes that have ensued on the occurrence of vascular occlusion are characterized by complete necrosis of the nervous tissues in the center. This occurred much more rapidly in the white than the gray matter where the ganglion cell layers became converted into a structureless mass. The tissue reactions involved both the glia and the mesodermal tissue. In the former, the changes were of two kinds: (1) the development of cytoplasmic glia and gitter cells. These latter infiltrated the whole central region and entered the adventitial sheaths of the vessels where they were surrounded by connective tissue fibrils; (2) at the periphery of the lesion especially, the development of glia fibers. In the smallest lesions these constituted the principal reaction and the final result was a glial scar. The mesodermic reaction included active fibrous proliferation and new vessel formation, with proliferation of lymphocytes. These connective tissue elements had invaded the necrosed area and the central region of softening.
Who is nutritionally vulnerable in Bosnia-Hercegovina?
Authors: J. Vespa, F. Watson
Journal: BMJ (1995)

<h3>Abstract</h3> <b>Objective</b>: To monitor nutritional status and food security in order to identify nutritionally vulnerable groups. <b>Design</b>: Members of five different household groups (urban and rural residents, displaced people in collective centres and private accommodation, elderly people living without younger family) and all residents of two old people9s homes were prospectively followed. Households were selected from 20 local communities and nine collective centres. <b>Setting</b>: Monitoring carried out in three besieged areas of Bosnia-Hercegovina (Sarajevo, Tuzla, and Zenica). <b>Subjects</b>: 1739 individuals sampled. <b>Interventions</b>: Data collected every month from December 1993 to May 1994. Information on household food security was collected through structured questionnaires. All subjects were weighed and their heights measured. Weight for age Z scores were calculated for children; body mass index was calculated for adults and elderly people. <b>Results</b>: From December 1993 to February 199 <b>Conclusions</b>: Elderly people in Bosnia-Hercegovina are at greater risk of undernutrition than other age groups. Undernutrition may be precipitated in elderly people by sickness, cold, stress, and problems related to food preparation. The health and welfare of elderly people during the emergency in Bosnia-Hercegovina require special attention, and integrated age care programmes are needed.
Haemostasis in fulminant hepatic failure.
Authors: P T Flute
Journal: BMJ (1971)

different treatments.Saunders carries out an exchange trans- fusion routinely if the patient remains in deep coma after 24 hours.In another personal series (from the Hospital Beaujon, Clichy) the results were quite different.1"Between 1952 and 1969 77 patients with severe viral hepatitis were seen, of whom 75 were in coma.Of 56 patients treated conservatively 13 survived, whereas there were no survivors in the 21 treated by corticosteroids, exchange transfusion, cross circula- tion, or hyperbaric oxygen.However, it is again quite likely that the more severe cases were treated by the more active measures.In the F.H.F.S. study of 101 patients in whom no treatment procedures were undertaken 10% survived,' while 24% of 166 patients lived in whom exchange transfusions were done.Thus no firm conclusions can be drawn about the value of exchange transfusion in the management of fulminant hepatic failure.Indeed the preliminary results in the first randomly allocated and controlled trial of exchange transfusion in fulninant hepatitis shows a higher mortality in the treated group."7
Fooling the liver: Malaria incognito
Authors: Mark D. Gorrell, Fiona J. Warner
Journal: Hepatology (2007)

The merozoite stage of the malaria parasite that infects erythrocytes and causes the symptoms of the disease is initially formed inside host hepatocytes. However, the mechanism by which hepatic merozoites reach blood vessels (sinusoids) in the liver and escape the host immune system before invading erythrocytes remains unknown. Here, we show that parasites induce the death and the detachment of their host hepatocytes, followed by the budding of parasite-filled vesicles (merosomes) into the sinusoid lumen. Parasites simultaneously inhibit the exposure of phosphatidylserine on the outer leaflet of host plasma membranes, which act as "eat me" signals to phagocytes. Thus, the hepatocyte-derived merosomes appear to ensure both the migration of parasites into the bloodstream and their protection from host immunity.
Significance of discordant ST alternans in ventricular fibrillation.
Authors: T Konta, K Ikeda, M Yamaki, K Nakamura, K Honma, I Kubota, S Yasui
Journal: Circulation (1990)

With the use of epicardial mapping, we investigated the electrical alternans of the ST segment during acute myocardial ischemia and studied the difference in ST alternans between dogs with resultant ventricular fibrillation and those without it. During the 7-minute occlusion of the left anterior descending coronary artery below its first diagonal branch, 60 epicardial unipolar electrograms were recorded simultaneously at 1-minute intervals by a computerized mapping system. ST alternans was found in the eight dogs we observed. The amplitude of ST alternans (difference in the ST segment elevation of two consecutive electrograms) was greater in dogs with ventricular fibrillation (n = 4) than in those without it (n = 4) (3.92 +/- 1.24 versus 0.58 +/- 0.49 mV, p less than 0.05). Three of the four dogs with ventricular fibrillation demonstrated discordant ST alternans (i.e., adjacent leads were out of phase). Results from the present study indicate that an increased amplitude and discordance of ST alternans during acute myocardial ischemia are related to ventricular fibrillation and act as indicators of time and spatial unevenness of ventricular repolarization.
Smoking ban is upheld at Scotland's State Hospital despite patient's earlier victory
Authors: B. Christie
Journal: BMJ (2014)

A patient at the State Hospital in Carstairs, Scotland, has failed in his bid to overturn a ban on smoking at the secure psychiatric establishment. Charles McCann, who has schizophrenia and has been detained for 18 years, was successful last year in getting a court ruling that the ban was unlawful and breached his human rights.1 That decision has now been reversed by three judges after the hospital appealed.

Smoking was banned in the buildings and grounds of the …
A Variant in the Cytochrome P450 Oxidoreductase Gene Is Associated with Breast Cancer Risk in African Americans
Authors: Christopher A. Haiman, V. Wendy Setiawan, Lucy Y. Xia, Loïc Le Marchand, Sue A. Ingles, Giske Ursin, Michael F. Press, Leslie Bernstein, Esther M. John, Brian E. Henderson
Journal: Cancer Research (2007)

Abstract Variation in the cytochrome P450 oxidoreductase (POR) gene, a key regulator of type II cytochrome P450 enzymes, may affect exposure to endogenous steroid hormones and breast cancer risk. We sequenced the POR locus and tested candidate polymorphisms G5G and A503V for association with breast cancer risk among women in the Multiethnic Cohort Study (1,615 cases and 1,962 controls). The single nucleotide polymorphism (SNP) A503V was common in all racial/ethnic populations (minor allele frequency, ≥0.05) but was not associated with risk. SNP G5G (A → G nucleotide change), which lies in a suggestive exonic splicing enhancer motif in exon 1, was common only in African Americans (minor allele frequency, 0.21) and the homozygous state was modestly associated with increased breast risk among all cases [345 cases and 426 controls; odds ratio (OR), 1.64; 95% confidence interval (CI), 0.89–3.04; P = 0.12] and among cases with advanced disease (95 cases: OR, 3.08; 95% CI, 1.42–6.70; P = 0.005). In an attempt to replicate this association, we genotyped SNP G5G in additional African American case-control studies (747 cases and 468 controls). Nonsignificant positive associations were noted with the GG genotype class in all studies. In the pooled analysis (1,038 cases and 877 controls with genotype data), the association was statistically significant among all cases (OR, 1.58; 95% CI, 1.04–2.41; P = 0.03) and stronger in those with advanced disease (411 cases and 877 controls; OR, 2.60; 95% CI, 1.56–4.34; P = 0.0002). These data suggest that African Americans harbor an allele at the POR locus that may increase breast cancer risk. [Cancer Res 2007;67(8):3565–8]
Abstract 121: Novel epigenetic mechanisms of resveratrol regulation of PTEN/Akt pathway in prostate cancer
Authors: Swati Dhar, Kun Li, Steven J. Dias, Anait S. Levenson
Journal: Cancer Research (2012)

Abstract Resveratrol (Res) (3,5,4′-trihydroxy-trans-stilbene), a natural compound found in grapes and berries, is one of the most promising diet-derived chemopreventive agent with potential chemotherapeutic capabilities. Chemopreventive and anticancer effects of Res may be exerted in part by modulating various components of the epigenetic machinery. We recently demonstrated that Res represses nucleosome remodeling and deacetylation (NuRD) co-repressor complex by inhibiting metastasis associated protein 1/ histone deacetylase 1 (MTA1/HDAC1) subunit, which plays an essential role in governing deacetylation of histone and non-histone proteins. Since Res-induced upregulation of tumor suppressor PTEN (phosphatase and tensin homolog deleted on chromosome 10) is concomitant with MTA1-downregulation, we hypothesized that in the absence of Res MTA1 works in cooperation with PI3K/Akt survival pathways. We further hypothesized that Res-induced restoration of PTEN expression and function may occur by dual mechanism through MTA1/HDAC inhibition and regulation of miRNA network. Our data indicate that shRNA-mediated MTA1 knockdown in Du145 cells (wt PTEN) enhances acetylation of PTEN, and that HDAC inhibitor trichostatin (TSA) further potentiates PTEN acetylation. We also showed that Res treatment simultaneously decreases MTA1 and pAkt levels in LNCaP cells, the effect which is enhanced in combination with PI3K inhibitors, LY294002 and BEZ235. To further understand Res-induced MTA1-mediated epigenetic alterations, we analyzed MTA1-associated and Res-induced microRNA (miRNA, miR) changes in LNCaP cells expressing and silenced for MTA1 (shMTA1). Interestingly, Res downregulated miRs (oncomiRs) included members of miR17-92 cluster (miRs-17, 20a, 20b) and miRs 106a and 106b which target PTEN. These findings were further confirmed by real time PCR analysis which showed that Res specifically down-regulated these miRNAs in PCa cells (LNCaP and Du145) but not in normal prostate cell line RWPE-1. Direct interaction of miR-17, miR-20a and miR-106b with PTEN 3′UTR were analyzed in the presence and absence of Res using pmiRGLO luciferase reporter. In summary, we propose novel epigenetic mechanisms of Res regulation of PTEN/ Akt signaling through inhibition of MTA1/NuRD co-repressor complex and MTA1-associated miRNAs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 121. doi:1538-7445.AM2012-121
Training and Conditioning Athletes: A Manual for Trainees and Physicians
Authors: Allan J. Ryan
Journal: JAMA (1971)

This is one of the best books produced so far for the use of athletic trainers. It is also a valuable guide to the team physician, especially for one who is being introduced to this specialized field for the first time. Comprehensive and up-to-date, it provides valuable references for more detailed study of important problems which cannot be treated in depth in a work of this kind. One of the great strengths of this book is the step-by-step procedures which are outlined and the check lists which are provided. Sample forms and letters which are simple and practical and good illustrations contribute to its usefulness. It is concise but also eminently readable, a virtue frequently lacking in books in this field. Where etiology of therapy is controversial, both sides are presented fairly and then the authors indicate their preferences. Although one might cavil at some of the decisions, this does
Effects of Chronic Hypoxemia on the Afferent Nerve Activities from Skeletal Muscle
Authors: ERICK DOUSSET, PATRICK DECHERCHI, LAURENT GRELOT, YVES JAMMES
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

An acute reduction of the oxygen supply to contracting muscles not only affects their metabolism but also modifies their sensorimotor control through changes in afferent discharge of the group I and group III–IV nerve fibers, the latter playing a pivotal role in the protective mechanisms against muscle fatigue. The effects of chronic hypoxemia on the muscle sensitivity are totally unknown. In the present study, group I fibers (mechanosensory afferents) and group III–IV fibers (mechanosensory and chemosensory afferents) from the anterior tibial muscle were recorded in normoxemic and chronic hypoxemic rats. Hypoxemic rats breathed for 45 d a gas mixture containing 9.5 to 10% O2 in N2. The data were compared with those obtained in normoxemic animals of the same age. To activate the different muscle afferents, we used different test agents, including electrically induced fatigue (EIF), KCl, lactic acid injections, as well as tendon vibrations. The conduction velocity of all nerve fibers was significantly (p < 0.01) higher in hypoxemic rats than in the normoxemic group. Chronic hypoxemia significantly depressed the response of the group III–IV muscle afferents to KCl injections and even abolished their response to lactic acid and EIF. However, the response to tendon vibrations of the group I afferents was similar in hypoxemic and normoxemic rats. These results suggest that chronic hypoxemia markedly alters the chemosensitivity of the group III–IV muscle afferents, which may explain the higher fatigability of hypoxemic subjects.