tbuckley/cabot-search huggingface dataset:
Vitamin D deficiency and renal calcium transport in the rat.
Authors: M Yamamoto, Y Kawanobe, H Takahashi, E Shimazawa, S Kimura, E Ogata
Journal: Journal of Clinical Investigation (1984)

To examine the role of vitamin D in the renal tubular handling of calcium, clearance studies were performed in three groups of rats: group A rats fed a standard vitamin D-deficient diet (Ca 0.45%, P 0.3%) for 6 wk, were hypocalcemic with secondary hyperparathyroidism; group B rats fed the same diet as in group A but with high calcium (Ca 1.4%) and 20% lactose, were normocalcemic and without secondary hyperparathyroidism; group C rats fed the same diet as in group A but supplemented with 25 U of vitamin D3 orally twice a week, were normocalcemic, vitamin D-replete, and euparathyroid. After thyroparathyroidectomy (TPTX), each rat was infused intravenously with an electrolyte solution that contained a fixed concentration of calcium (0-30 mM) with or without parathyroid hormone (PTH; 0.75 or 2.5 U/h) at a rate of 3 ml/h. Urinary calcium excretion and serum calcium concentrations were measured between 16 and 19 h of the infusion, and the apparent threshold of calcium excretion was determined. The threshold of calcium excretion was lower in vitamin D-deficient TPTX rats (groups A and B) than in vitamin D-replete TPTX rats (group C), and not different between group A and group B. Administration of PTH at a dose of 0.75 U/h increased the threshold of calcium excretion by approximately 0.6 mM in group C, but did not alter the threshold either in group A or group B. Administration of a higher dose of PTH (2.5 U/h) raised the threshold similarly in both group A and group B to the extent comparable with that in group C, when it was given 0.75 U/h of PTH. These results demonstrate that the renal threshold of calcium excretion is decreased in the vitamin D-deficient rats independent of the secondary hyperparathyroidism, and that the higher dose of PTH was necessary to raise the calcium threshold in vitamin D-deficient rats. Thus, present study indicates the presence of dual effects of vitamin D on renal tubular handling of calcium; the one is to facilitate renal calcium reabsorption and the other is to enhance the responsiveness of the tubule to PTH.
Potential New Cardiovascular Risk Factors: Left Ventricular Hypertrophy, Homocysteine, Lipoprotein(a), Triglycerides, Oxidative Stress, and Fibrinogen
Authors: Kishore J. Harjai
Journal: Annals of Internal Medicine (1999)

The 1996 Bethesda Conference acknowledged left ventricular hypertrophy, hyperhomocysteinemia, lipoprotein(a) excess, hypertriglyceridemia, oxidative stress, and hyperfibrinogenemia as possible new cardiac risk factors. This review summarizes the current literature that supports these conditions as cardiac risk factors. Left ventricular hypertrophy is an independent risk factor for vascular disease. Improvement or progression of left ventricular hypertrophy influences subsequent cardiovascular complications. Clinical trials are under way to assess the potential benefit of decreasing homocysteine levels. The role of lipoprotein(a) excess in vascular disease is controversial. The atherogenic potential of lipoprotein(a) seems to be neutralized by effective reduction of low-density lipoprotein cholesterol levels. Increasing evidence supports an independent role of hypertriglyceridemia in cardiovascular disease and a possible clinical benefit from decreasing triglyceride levels. Among antioxidant micronutrients, supplementation with vitamin E has been shown to be beneficial in primary and secondary prevention studies. Data supporting the use of other antioxidants are much weaker. Preliminary evidence suggests that reducing fibrinogen levels in patients with high baseline levels and coronary disease may be beneficial. Despite the potential relation between new risk factors and cardiovascular disease, routine clinical application of these conditions as cardiovascular risk factors would be premature. Evidence is needed that these conditions extend prognostic ability beyond conventional risk factors and that modification of these conditions can reduce the risk for cardiovascular events.
A crucial role for adipose tissue p53 in the regulation of insulin resistance
Authors: Tohru Minamino, Masayuki Orimo, Ippei Shimizu, Takeshige Kunieda, Masataka Yokoyama, Takashi Ito, Aika Nojima, Akira Nabetani, Yuichi Oike, Hisahiro Matsubara, Fuyuki Ishikawa, Issei Komuro
Journal: Nature Medicine (2009)
Adenovirus-mediated expression of Cu/Zn- or Mn-superoxide dismutase protects against CYP2E1-dependent toxicity
Authors: María José Pérez, Arthur I. Cederbaum
Journal: Hepatology (2003)

CYP2E1 induction by ethanol is one mechanism by which ethanol creates oxidative stress in the liver. The superoxide dismutases (SODs) are an important antioxidant enzyme defense system against reactive oxygen species (ROS). To investigate the protective role of SOD against CYP2E1-dependent toxicity, a transfected HepG2 cell line overexpressing CYP2E1 (E47 cells) was infected with adenoviral vectors containing Cu/Zn-SOD complementary DNA (cDNA) (Ad.SOD1) and Mn-SOD cDNA (Ad.SOD2). Forty-eight hours after infection, intracellular levels and activity of Cu/Zn-SOD and Mn-SOD were increased about 2- and 3-fold, respectively. Localization of the overexpressed Cu/Zn-SOD in the cytosol and Mn-SOD in the mitochondria was confirmed by assaying the levels and activity of SOD in the corresponding isolated fractions. Arachidonic acid (AA) plus iron-induced cell death was partially prevented in both Ad.SOD1- and Ad.SOD2-infected E47 cells. Overexpression of Cu/Zn-SOD and Mn-SOD also partially protected E47 cells from the increase in reactive oxygen production and lipid peroxidation and the loss of mitochondrial membrane potential induced by AA and iron. Infection with Cu/Zn-SOD and Mn-SOD also protected the E47 cells against AA toxicity or buthionine sulfoximine (BSO)-dependent toxicity. CYP2E1 levels and catalytic activity were not altered by overexpression of Cu/Zn-SOD or Mn-SOD. Cu/Zn-SOD in the cytosol and Mn-SOD in mitochondria each are capable of protecting HepG2 cells expressing CYP2E1 against cytotoxicity induced by pro-oxidants. In conclusion, these enzymes may be useful in the prevention or improvement of liver injury produced by agents known to be metabolized by CYP2E1 to reactive intermediates and to cause oxidative stress.
Scientific Foundations of Surgery
Authors: John H. Wulsin
Journal: JAMA (1967)

Since the publication of the first edition of Scientific Foundations of Surgery in 1967, the initial work succeeded so well that a series of 15 Scientific Foundations volumes has appeared covering various specialties, such as neurology, anesthesia, and dentistry. While the original intent of the editors centered on having clinical authors discuss the basic research and pathophysiological principles underlying clinical problems (a book by surgeons for surgeons), subsequent editions have relied more on acknowledged investigators in pertinent fields of medical science. Although the first editors and most of the contributors hold positions in universities and hospitals throughout the British Commonwealth, the coeditor of the current edition, Dr James Hardy of the University of Mississippi, has selected an eminent group of American surgeons as contributors, most notably to the sections dealing with Immunology and Transplantation and with the Liver, Gallbladder and Ducts.  Compared with the second edition, this work has been
A 39-kb Sequence Around a Blackbird Mhc Class II Gene: Ghost of Selection Past and Songbird Genome Architecture
Authors: Scott V. Edwards, Joe Gasper, Daniel Garrigan, Duane Martindale, Ben F. Koop
Journal: Molecular Biology and Evolution (2000)

To gain an understanding of the evolution and genomic context of avian major histocompatibility complex (Mhc) genes, we sequenced a 38.8-kb Mhc-bearing cosmid insert from a red-winged blackbird (Agelaius phoeniceus). The DNA sequence, the longest yet retrieved from a bird other than a chicken, provides a detailed view of the process of gene duplication, divergence, and degeneration ("birth and death") in the avian Mhc, as well as a glimpse into major noncoding features of a songbird genome. The peptide-binding region (PBR) of the single Mhc class II B gene in this region, Agph-DAB2, is almost devoid of polymorphism, and a still-segregating single-base-pair deletion and other features suggest that it is nonfunctional. Agph-DAB2 is estimated to have diverged about 40 MYA from a previously characterized and highly polymorphic blackbird Mhc gene, Aph-DAB1, and is therefore younger than most mammalian Mhc paralogs and arose relatively late in avian evolution. Despite its nonfunctionality, Agph-DAB2 shows very high levels of nonsynonymous divergence from Agph-DAB1 and from reconstructed ancestral sequences in antigen-binding PBR codons—a strong indication of a period of adaptive divergence preceding loss of function. We also found that the region sequenced contains very few other unambiguous genes, a partial Mhc- class II gene fragment, and a paucity of simple-sequence and other repeats. Thus, this sequence exhibits some of the genomic streamlining expected for avian as compared with mammalian genomes, but is not as densely packed with functional genes as is the chicken Mhc.
Research misconduct is widespread and harms patients
Authors: F. Godlee
Journal: BMJ (2012)

The best writing transforms the writer as well as the reader. I can’t claim transformation for you when you read the editorial on research misconduct in the UK (doi:10.1136/bmj.d8357), but I do claim it for me. Writing it with Elizabeth Wager changed my own views, largely thanks to conversations with those we sent it to for comment.

The editorial prefaces a joint BMJ /COPE meeting on 12 January on research misconduct in the UK. As Aniket Tavare makes clear, the UK is lagging behind other developed countries in still having no proper system for tackling misconduct (doi:10.1136/bmj.d8212). Discussions and initiatives have focused on research fraud, defined as fabrication, …
Anaemia among patients with heart failure and preserved or reduced ejection fraction: results from the SENIORS study
Authors: Stephan von Haehling, Dirk J. van Veldhuisen, Michael Roughton, Daphne Babalis, Rudolf A. de Boer, Andrew J.S. Coats, Luis Manzano, Marcus Flather, Stefan D. Anker
Journal: European Journal of Heart Failure (2011)
OC-163 Identification of inflammatory bowel disease (IBD) using field asymmetric ion mobility spectrometry (FAIMS)
Authors: R Arasaradnam, N O Ouaret, M Thomas, E Hetherington, M N Quraishi, C Nwokolo, K D Bardhan, J Covington
Journal: Gut (2012)

<h3>Introduction</h3> Resident colonic bacteria, principally anaerobes and firmicutes, ferment undigested fibre. The resultant volatile organic compounds (VOCs) formed are dissolved in the faeces but also absorbed and excreted in the urine. We have previously shown that electronic nose (E-nose) analysis of urine VOCs distinguishes between Crohn9s disease (CD), ulcerative colitis (UC) and healthy volunteers (HV): the underlying principle is pattern recognition of disease-specific “chemical fingerprint”. High-Field Asymmetric Waveform Ion Mobility Spectrometry (FAIMS) offers a possible alternative. The underlying principle is separation of VOC chemical components based on their different ion mobilties in high electric fields. We performed a pilot study in the above groups, the patients in remission (Rem) or with active disease (AD), to assess if this technology could achieve separation between the groups. The results were validated against E-nose analysis. <h3>Methods</h3> 59 subjects were studied; HV n=14, UC (Rem) n=18, UC (AD) n=4; CD (Rem) n=19, CD (AD) n=4. Urine samples (7 ml) in universal containers (25 ml) were heated to 40±0.1 C. The headspace (the air above the sample) was then analysed using FAIMS. The data were analysed by Fisher Discriminant Analysis. <h3>Results</h3> The technique distinguished between the three groups. Additionally, patients with active disease could be distinguished from those in remission. These results were concordant with E-nose analysis. <h3>Conclusion</h3> This pilot shows that urine VOCs, analysed by the different approaches of E-nose and FAIMS, the latter a novel application, can distinguish the healthy from those with UC and CD when disease is active or in remission. The two technologies together offer a non-invasive approach to diagnosis and follow-up in inflammatory bowel disease. <h3>Competing interests</h3> None declared.
What is a Health Care Trial?
Authors: Walter O. Spitzer
Journal: JAMA (1975)

ALTHOUGH most people know what to expect as topics of the research conducted in such domains as biochemistry, microbiology, or epidemiology, the domain of health care research has not been clearly delineated. It sometimes seems to include a chaotic variety of activities, ranging from polemic debates about medical ethics to quantitative accounts of hospital finances to biostatistical experiments with randomized therapy. The heterogeneous components and varieties of such research create special problems for peer review committees and for administrators of agencies that support health care research. Because the distinctive features of the research have not been precisely demarcated, it is often difficult to reach a consensus about the merit or even the eligibility of projects under consideration. To help clarify some of the confusion, we have written this article for the taxonomic purpose of defining and classifying the kinds of investigation that constitute health care research. Health care research is
Treatment of cancer in sub-Saharan Africa
Authors: T Peter Kingham, Olusegun I Alatise, Verna Vanderpuye, Corey Casper, Francis A Abantanga, Thaim B Kamara, Olufunmilayo I Olopade, Muhammad Habeebu, Fatimah B Abdulkareem, Lynette Denny
Journal: The Lancet Oncology (2013)
Bagging with CTD – A Novel Signature for the Hierarchical Prediction of Secreted Protein Trafficking in Eukaryotes
Authors: Geetha Govindan, Achuthsankar S. Nair
Journal: Genomics Proteomics & Bioinformatics (2013)

Protein trafficking or protein sorting in eukaryotes is a complicated process and is carried out based on the information contained in the protein. Many methods reported prediction of the subcellular location of proteins from sequence information. However, most of these prediction methods use a flat structure or parallel architecture to perform prediction. In this work, we introduce ensemble classifiers with features that are extracted directly from full length protein sequences to predict locations in the protein-sorting pathway hierarchically. Sequence driven features, sequence mapped features and sequence autocorrelation features were tested with ensemble learners and their performances were compared. When evaluated by independent data testing, ensemble based-bagging algorithms with sequence feature composition, transition and distribution (CTD) successfully classified two datasets with accuracies greater than 90%. We compared our results with similar published methods, and our method equally performed with the others at two levels in the secreted pathway. This study shows that the feature CTD extracted from protein sequences is effective in capturing biological features among compartments in secreted pathways.
TCT-101 Prognostic role of restenosis in 10,004 patients undergoing routine control angiography after coronary stenting
Authors: Salvatore Cassese, Robert Byrne, Stefanie Schulz, Petra Hoppmann, Tareq Ibrahim, Ilka Ott, Massimiliano Fusaro, Heribert Schunkert, Karl-Ludwig Laugwitz, Adnan Kastrati
Journal: Journal of the American College of Cardiology (2014)
Use of paroxetine during tamoxifen therapy for breast cancer was associated with increased breast-cancer and all-cause mortality
Authors: Bruce E. Hillner
Journal: Annals of Internal Medicine (2010)

Source Citation Kelly CM, Juurlink DN, Gomes T, et al. Selective serotonin reuptake inhibitors and breast cancer mortality in women receiving tamoxifen: a population based cohort study. BMJ. 2010;340;c693. 20142325
Circumcision in a National Sample of 4-year-old Children
Authors: D. MacCarthy, J. W. B. Douglas, C. Mogford
Journal: BMJ (1952)

The radiological picture of acute Friedliinder's pneumonia may resemble that of ordinary pneumonic consolidation, but, as was pointed out by Bullowa et al. (1937), the most striking finding initially is the density of the shadow, which is usually homogeneous and may be suggestive of fluid.A bronchopneumonic phase was described by Kornblum (1928).This was not seen in these cases.After a day or two one notices less-opaque areas due to the formation of abscesses.It is sometimes found that there is bulging or sagging of the interlobar septa, and this is well illustrated in the recent paper by Kirby and Coleman (1951), who reported it in half of their 11 cases.As the chronic stage is reached fibrosis makes its appearance, combined with a honeycomb effect due to small cavities.Keefer et al. (1946), in their clinical trials, found strepto- mycin effective if given early in lung infections due to Friedlander's bacillus.Chloramphenicol and aureomycin have also produced good results in small series.We found records of 38 cases treated with streptomycin, chlor- amphenicol, aureomycin, or combinations of these anti- biotics.In these the mortality rate was 37%.We were impressed by the rapid downhill course of Case 4, who at 49 years was the youngest of the series.Rapid bacterio- logical diagnosis is still important in pneumonia.Our routine is to collect sputum at the initial clinical examination.Some of this is stained by Gram's method.If Gram- negative bacilli are found to be the predominant organism, streptomycin, I g.eight-hourly, is given pending the result of sputum culture.No cases have been seen since aureo- mycin became freely available.We intend to substitute it for streptomycin.
δ-Aminolevulinic Acid Dehydratase Activity in Circulating Blood Cells
Authors: Joseph B. Weissberg, Fred Lipschutz, Frank A. Oski
Journal: New England Journal of Medicine (1971)

Original Article from The New England Journal of Medicine — δ-Aminolevulinic Acid Dehydratase Activity in Circulating Blood Cells — A Sensitive Laboratory Test for the Detection of Childhood Lead Poisoning
Steatorrhoea in the elderly.
Authors: H L Price, B G Gazzard, A M Dawson
Journal: BMJ (1977)

Steatorrhoea which may occasionally present in middle or old age, is a treatable cause of diarrhoea. The possible causes based on a pathophysiological classification are innumerable.' We therefore thought it pertinent to analyse our experience of patients who presented over the age of 50 to find out the most likely cause in practice and assess the most useful diagnostic clinical and laboratory features.
The Molecular-Genetic Basis of Functional Hyperandrogenism and the Polycystic Ovary Syndrome
Authors: Héctor F. Escobar-Morreale, Manuel Luque-Ramírez, José L. San Millán
Journal: Endocrine Reviews (2005)

The genetic mechanisms underlying functional hyperandrogenism and the polycystic ovary syndrome (PCOS) remain largely unknown. Given the large number of genetic variants found in association with these disorders, the emerging picture is that of a complex multigenic trait in which environmental influences play an important role in the expression of the hyperandrogenic phenotype. Among others, genomic variants in genes related to the regulation of androgen biosynthesis and function, insulin resistance, and the metabolic syndrome, and proinflammatory genotypes may be involved in the genetic predisposition to functional hyperandrogenism and PCOS. The elucidation of the molecular genetic basis of these disorders has been burdened by the heterogeneity in the diagnostic criteria used to define PCOS, the limited sample size of the studies conducted to date, and the lack of precision in the identification of ethnic and environmental factors that trigger the development of hyperandrogenic disorders. Progress in this area requires adequately sized multicenter collaborative studies after standardization of the diagnostic criteria used to classify hyperandrogenic patients, in whom modifying environmental factors such as ethnicity, diet, and lifestyle are identified with precision. In addition to classic molecular genetic techniques such as linkage analysis in the form of a whole-genome scan and large case-control studies, promising genomic and proteomic approaches will be paramount to our understanding of the pathogenesis of functional hyperandrogenism and PCOS, allowing a more precise prevention, diagnosis, and treatment of these prevalent disorders.
CLINICAL CIRCULATORY EFFECTS OF DINITROPHENOL
Authors: A. B. STOCKTON
Journal: JAMA (1934)

During the clinical use of sodium dinitrophenol (1-2-4) in obese patients, the occasional appearance of subjective symptoms such as tachycardia, dyspnea and profuse diaphoresis<sup>1</sup>suggested the necessity of investigating the effects of the drug on the circulation. Thirteen patients with apparently normal cardiovascular systems were selected for this study. Six of the group were placed at bed rest in the hospital, and control observations of blood pressure, pulse rate, vital capacity and venous pressure made regularly at 8 a. m., 2 p. m. and 7 p. m. The control period was continued until at least three consecutive results were in close agreement. A mean of three or more control results was taken as the base. The control period was never less than three days and was sometimes as long as five days. A quantity of 300 mg. of sodium dinitrophenol was then administered orally in three divided doses each day,
Lower respiratory illness, recurrent wheezing, and day care attendance.
Authors: M C Marbury, G Maldonado, L Waller
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

We prospectively assessed the relations between various characteristics of day care and lower respiratory illness (LRI) in a cohort of 1,268 Minnesotan children, born between October 1989 and January 1991 and followed to 2 yr of age. Information on LRI was abstracted from medical records and data on day care use, respiratory symptoms, and physician diagnosis of asthma were obtained from questionnaires. We identified a subgroup of 60 children with recurrent wheezing illnesses. The LRI rate ratio for day care attendance was 2.0 (95% confidence interval = 1.7, 2.2). Rate ratios were similar regardless of the day care setting, number of other children present, or the number of hours spent in day care. A parental history of asthma further increased the rate ratio for day care attendance. Day care attendance was associated with a threefold risk of having recurrent wheezing illnesses. We conclude that day care attendance is an important risk factor for LRI in young children, and for recurrent wheezing illnesses.