tbuckley/cabot-search huggingface dataset:
Identity of the M2 autoantigens in primary biliary cirrhosis
Authors: Ian R. Mackay, Merrill J. Rowley, John McD. Armstrong
Journal: Hepatology (1989)

Primary biliary cirrhosis (PBC)-specific antigens were purified from beef heart mitochondria by immunoaffinity chromatography. Three major polypeptides (75, 60, and 40 kDa) were detected in the purified antigen fraction both by Coomassie blue staining and by western blot analysis. The 75 kDa antigen was identified as a subunit of Complex I (NADH-ubiquinone reductase) by the following criteria: (1) antibodies against the purified 75 kDa subunit of beef heart Complex I react with the immunoaffinity-purified 75 kDa antigen, (2) the 75 kDa subunit present in isolated Complex I, like that in the immunoaffinity-purified antigen, reacts with PBC sera only after reduction with mercaptoethanol, and (3) the 75 kDa antigen is enriched in isolated Complex I. A relationship between the 75 kDa and the 60 and 40 kDa antigens is suggested, since optimal binding of anti-mitochondrial autoantibodies (AMA) to the latter antigens also requires prior reduction with mercaptoethanol. A fourth major antigen (70 kDa) was also detected by western blot analysis, but only in samples that had not been boiled prior to electrophoresis. This antigen, which is also present in isolated Complex I, resembles the 75, 60, and 40 kDa antigens in its response to mercaptoethanol and its reaction with antibodies against the 75 kDa subunit of Complex I. A scheme is presented which relates all of the PBC antigens to the parent 75 kDa subunit of Complex I, probably as proteolytic products of the latter.
Amelioration of the severity of heparin-binding antithrombin mutations by posttranslational mosaicism
Authors: Irene Martínez-Martínez, José Navarro-Fernández, Alice Østergaard, Ricardo Gutiérrez-Gallego, José Padilla, Nataliya Bohdan, Antonia Miñano, Cristina Pascual, Constantino Martínez, María Eugenia de la Morena-Barrio, Sonia Águila, Shona Pedersen, Søren Risom Kristensen, Vicente Vicente, Javier Corral
Journal: Blood (2012)
Oxygen Cost of Electrical Activation of the Heart
Authors: Francis J. Klocke, Eugene Braunwald, John Ross.
Journal: Circulation Research (1966)

The present study was undertaken to define the O 2 requirements of electrical activation of the heart. Thirteen isolated canine hearts were perfused with whole blood from which calcium had been removed with an exchange resin and to which the disodium salt of ethylenediaminetetraacetic acid had been added. Spontaneous depolarizations were suppressed by raising the plasma potassium to an average concentration of 7.5 mEq/liter, and the right ventricle was stimulated electrically at controlled frequencies. Although the stimuli produced propagated depolarizations, neither high-sensitivity strain gauge arches sutured to both ventricles, nor careful visual observation, showed any evidence of associated contractile activity. Ten of the hearts were studied with repetitive single stimuli applied in the conventional fashion, while the remaining three hearts were subjected to paired electrical stimulation. Changes of myocardial O 2 consumption (MV · O 2 ) were measured at a constant coronary blood flow and arterial O 2 content by determining changes of venous O 2 content from a continuous recording of venous PO 2 . Increases of the frequency of depolarization were uniformly accompanied by small increases of MV · O 2 , averaging 0.40 ± 0.04 (SEM) µliter/activation/100 g. The increases were of the same order of magnitude in the hearts subjected to paired electrical stimulation as in the hearts studied with single stimulation, suggesting that the altered frequency and rhythm of depolarization in paired electrical stimulation cannot account for the marked increase of MV · O 2 which this intervention produces in the intact heart. It is concluded that the amount of O 2 required for electrical activation of the heart is less than 1% of the total O 2 consumption of the normally working heart.
A Vascular Abnormality in Hypertension
Authors: JAMES CONWAY
Journal: Circulation (1963)

Forearm blood flow measurements have been made at rest and after 8 to 10 minutes arterial occlusion in 50 normal and 131 untreated hypertensive subjects. The latter group comprised 91 with essential hypertension; 11 with chronic renal disease (nephritis or pyelonephritis); 21 with renovascular disease; and eight with primary aldosteronism. The resting blood flow increased with the rising pressure in patients with mild hypertension but there was a significant increase in the resting resistance in the more severe cases. The average minimal resistance obtained during reactive hyperemia was greater in hypertensive (3.1 SE 1.0 units) than in normal subjects (2.0 SE 0.07 units). This abnormality was related to the level of blood pressure but not to the duration of the disease. Patients with renovascular disease or aldosteronism presented the same vascular fault as the more common causes of hypertension. Evidence is presented to show that the reactive hyperemia produced maximal dilatation of the forearm vasculature, and acute elevation in pressure in normotensive or acute depression of pressure in hypertensive subjects did not influence the level of resistance achieved by reactive hyperemia. It is concluded that the blood vessels themselves are abnormal in hypertension and that this abnormality may not be related to the activity of vascular smooth muscle.
Fish mesonephric model of polycystic kidney disease in medaka (Oryzias latipes) pc mutant
Authors: Emiko Mochizuki, Katsuhiro Fukuta, Tatsuya Tada, Tomohiro Harada, Naoki Watanabe, Seiichi Matsuo, Hisashi Hashimoto, Kenjiro Ozato, Yuko Wakamatsu
Journal: Kidney International (2005)
Sensitivity, Specificity, and Predictive Values in the 'Sensitivity and Specificity of Clinical Diagnostics'
Authors: Hampton R. Bates
Journal: JAMA (1989)

<h3>To the Editor.—</h3> The article concerning postmortem evaluation of clinical diagnostics during five decades<sup>1</sup>is a good effort to analyze disparate data that can be resistant to marshaling by ordinary statistical methods. However, I think that the true-negative category, within the constraints of this study, is largely a passive statistic that sheds little light on the diagnostic process. This occurs because the act of making a clinical diagnosis leads to a mutually exclusive binomial distribution of that diagnosis vs a statistical universe of other diagnoses, many of which are trivial. On the other hand, "agreed" (true positives), "underdiagnosed" (false negatives), and "overdiagnosed" (false positives) are intuitively satisfying categories that present a more realistic picture of actual practice. Another statistical method avoids the true-negative dilemma by using only those cells of the fourfold (2 × 2) tables that can be occupied by at least one positive diagnosis (clinical or autopsy).
The Satb1 Protein Directs Hematopoietic Stem Cell Differentiation toward Lymphoid Lineages
Authors: Yusuke Satoh, Takafumi Yokota, Takao Sudo, Motonari Kondo, Anne Lai, Paul W. Kincade, Taku Kouro, Ryuji Iida, Koichi Kokame, Toshiyuki Miyata, Yoko Habuchi, Keiko Matsui, Hirokazu Tanaka, Itaru Matsumura, Kenji Oritani, Terumi Kohwi-Shigematsu, Yuzuru Kanakura
Journal: Immunity (2013)
Clinical academic medicine: a Socratic dialogue
Authors: D G Grahame-Smith
Journal: BMJ (1997)

As in all walks of life, clinical academic medicine has many vested interests, some acting for the greater good, some not.Socrates has a penchant for sniffing out pretension and sectional interest.Hippocrates is a thoughtful, gentlemanly physician unaccustomed to ensnarement by Socratic wiles, and when he and Socrates meet one day in the marketplace in Athens the following conversation about the state of clinical academic medicine ensues.It is not a dialogue for the timid.socrates: Hippocrates, you are looking rather down in the mouth.What's up? hippocrates: I am having a sabbatical from my clinical labours to spend time thinking about medical academic and scientific matters.socrates: How interesting.I had always thought of you as a proper doctor, not an academic one.hippocrates: Sometimes, Socrates, you can be so wounding.How can I explain to you the difference between an everyday hardworking physician in service and one who, while active in clinical work, also has an obligation to teach and by original research to forward his subject?socrates: Are not research and practice compatible?hippocrates: To some extent they are.Indeed, those who are not labelled "clinical academics," if they are enthusiastic clinicians with a love of order, can and do study their patients and make important and useful contributions to practice.socrates: How does that differ from the sort of research you do? hippocrates: I have always been interested in the molecular causes of disease.socrates: What use is that?hippocrates: Without such understanding, there can be no rational progress towards treatments and cures as yet undiscovered.
National Suicide Rates 1961–2003: Further Analysis of Nordic Data for Suicide, Autopsies and Ill-Defined Death Rates
Authors: Svein Reseland, Joanna Le Noury, Graham Aldred, David Healy
Journal: Psychotherapy and Psychosomatics (2008)

&lt;i&gt;Background:&lt;/i&gt; Concerns about the risk-benefit ratio of treatment with antidepressants in the light of recent evidence pointing to a risk of suicide induction during the course of treatment with antidepressants. These concerns have led to a series of recent studies exploring national rates of suicide and correlating these with data on antidepressant consumption. &lt;i&gt;Methods:&lt;/i&gt; We have compared suicide rates in the Nordic countries with autopsy and ill-defined death rates, and antidepressant sales, during the period 1961 through to 2003. &lt;i&gt;Results:&lt;/i&gt; There is a close correlation between suicide rates and both autopsy and ill-defined death rates. &lt;i&gt;Conclusions:&lt;/i&gt; The role of autopsies and other factors in the registration of a death as a suicide appear to need further clarification.
Dexfenfluramine in Obese Chinese NIDDM Patients: A placebo-controlled investigation of the effects on body weight, glycemic control, and cardiovascular risk factors
Authors: Chun-Chung Chow, Gary TC Ko, Lynn WW Tsang, Vincent TF Yeung, Juliana CN Chan, Clive S Cockram
Journal: Diabetes Care (1997)

OBJECTIVE To investigate the safety, efficacy, and metabolic effects of dexfenfluramine in obese Chinese NIDDM patients. RESEARCH DESIGN AND METHODS Thirty-two patients, mean (± SD) body weight 76.2 ± 8.5 kg with corresponding BMI 31.1 ± 2.1 kg/m2, were randomized into a two-phase study, after a 2-week single-blind run-in period on placebo. Phase 1 was a randomized 3-month double-blind placebo-controlled trial during which either dexfenfluramine or placebo was added to the existing treatment regimens of diet plus or minus sulfonylureas without metformin. Phase 2 was a further 3-month single-blind trial during which the placebo group was given dexfenfluramine without patients' knowledge of changing to active medication, while the active group continued with dexfenfluramine. Body weight, glycemic control, blood pressure, lipids, and quality of life were assessed before and at 3 and 6 months after randomization. A total of 27 patients were also followed for an additional period of 6–12 months (215 ± 53 days) after dexfenfluramine treatment was withdrawn. RESULTS During the run-in period, both groups were comparable for all parameters measured. At 3 months, mean changes in BMI were −1.2 ± 1.0 kg/m2 (dexfenfluramine) vs. −0.1 ± 0.5 kg/m2 (placebo) (P &amp;lt; 0.001). The mean changes in fasting plasma glucose were −1.14 ± 0.99 vs. 0.51 ± 1.34 mmol/l (dexfenfluramine vs. placebo, P = 0.004). HbA1c also significantly improved in the dexfenfluramine group (−0.80 ± 0.53 vs. 0.25 ± 0.64%, P &amp;lt; 0.001). During the 3-month single-blind dexfenfluramine treatment in the ex-placebo group, there were similar improvements in body weight and glycemic indexes. After cessation of dexfenfluramine therapy at 6 months, significant increases in body weight and glycemic indexes, almost back to the baseline, were observed for both groups. CONCLUSIONS Dexfenfluramine aids weight loss and improves glycemic control in obese Chinese NIDDM patients over a 3- to 6-month period. These effects are emphasized after withdrawal of treatment and further support the longer-term use of dexfenfluramine for chronic complicated obesity.
Abstract 387: PEDF binds to IL- 10 receptor in the absence of IL-10 and inhibits melanoma tumor growth
Authors: Aslam A. Khan
Journal: Cancer Research (2012)

Abstract Macrophages exist within the tumor microenvironment and play an important role in influencing tumor cell growth, angiogenesis and cancer progression. The interaction between macrophages, tumor cells, and endothelial cells occurs largely through cytokine secretion and detection by tumor associated macrophages (TAM). In this study, we investigate the role of interleukin-10 (IL-10) and pigment epithelial derived factor (PEDF) in the macrophage-tumor interaction. In an explant model of melanoma, tumor growth was significantly reduced in IL-10 knockout mice. Media from IL-10 deficient macrophages significantly inhibited tumor cell proliferation when compared to media from wild-type macrophages. Interestingly, expression of the anti-tumor and anti-angiogenic cytokine PEDF was increased in IL-10 knockout macrophages. Media of IL-10 KO macrophages treated with recombinant IL-10 (rIL-10) and anti-PEDF failed to inhibit tumor cell proliferation. Neutralization of PEDF in IL-10 KO mice restored tumor growth in these mice. To further explore the molecular mechanisms of the interaction between PEDF, IL-10 and IL-10 receptor, IL-10 receptor binding of PEDF was evaluated in presence or absence of rIL-10. PEDF binds to IL-10 receptor only in the absence of competing rIL-10. Taken together these studies show a novel interaction between PEDF and the IL-10 receptor and suggest that the anti-tumor activity of PEDF can be significantly enhanced by reducing IL-10 levels. 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 387. doi:1538-7445.AM2012-387
Where the boys aren't: dioxin and the sex ratio
Authors: Richard Clapp, David Ozonoff
Journal: The Lancet (2000)

Dioxins have the well-deserved reputation of being the most potent man-made biological agents and, along with their biological/chemical cousins, the coplanar poly-chlorinated biphenyl and polychlorinated dibenzofurans, they are ubiquitous in the environment, although usually at low concentrations. The low concentrations can become biologically magnified in the food chain as these lipophilic and hydrophobic substances get concentrated during their move from soil and sediment to fish or animal feed, to dairy and meat products, and eventually to the top of the food chain, human beings. Two Research Letters in today's Lancet show how contamination of the oceans, and of animal feed, can produce significant exposure of human beings to dioxins. Also in this issue of The Lancet is an article, by Paolo Mocarelli and colleagues, which provides intriguing and worrying results of how exposure to dioxins might affect people who consume dioxin-contaminated food. High fish-specific dioxin concentrations in FinlandDioxin concentrations in a population that frequently eat fish from the Baltic Sea are comparable to those seen in inhabitants of Seveso, Italy, after the accidental release of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in 1976. Individual variations in the congener patterns in human beings are similar to congener patterns in the fish species consumed. Full-Text PDF Dioxin contamination of feed and foodA preventive action limit for dioxins in feed for broiler chickens and pigs was set to 2 pg toxic equivalents/g feed in Austria. This limit was effective in the detection of feed contamination from an imported mineral additive, and in the prevention of food contamination according to WHO tolerable daily intake. Full-Text PDF Paternal concentrations of dioxin and sex ratio of offspringExposure of men to TCDD is linked to a lowered male/female sex ratio in their offspring, which may persist for years after exposure. The median concentration of dioxin in fathers in this study is similar to doses that induce epididymal impairments in rats and is about 20 times the estimated average concentration of TCDD currently found in human beings in industrialised countries. These observations could have important public-health implications. Full-Text PDF
Urinary markers for exposures to alkylating or nitrosating agents.
Authors: J S Wishnok, S R Tannenbaum, W G Stillwell, J A Glogowski, C D Leaf
Journal: Environmental Health Perspectives (1993)

Investigation of urinary markers as indices of endogenous nitrosation and of gastric cancer etiology has been a major focus of our work. As part of this effort, studies have been carried out on a Colombian population at high risk for gastric cancer. In this group, nitrosoproline excretion was highly correlated with nitrate excretion in the subpopulation with advanced gastric pathology, but not in control subpopulations with more normal stomachs. Neither urinary 7-methylguanine nor 3-methyladenine was strongly related to gastric pathology or to urinary nitrate or nitrosoproline levels. More recently, as evidence has accumulated concerning the importance of nitric oxide as a cellular messenger, we have begun research toward developing markers for the presence of nitric oxide and for endogenous nitrosation via this compound. Nitric oxide is formed from arginine by activated endothelial cells as a messenger for vasodilation. We have shown that prolonged exercise leads to increased urinary nitrate and that when 15N-arginine is ingested by humans, 15N-nitrate levels increase in 24-hr urine collections. Nitrosohydroxyethylglycine and 3-nitrotyrosine were evaluated as indices for the formation of N-nitrosomorpholine and for the nitration of protein, respectively, under experimental conditions (e.g., immunostimulation) expected to enhance nitric oxide formation. Nitrotyrosine has not proved useful as a biomarker for nitration/nitrosation reactions in immunostimulated rats. Immunostimulation of rats following administration of morpholine led to increases in urinary nitrate and nitrosohydroxyethylglycine. This procedure, however, would not be appropriate for humans due to the toxicity of morpholine and the carcinogenicity of N-nitrosomorpholine.
The Role of Soy Products in Reducing Risk of Cancer
Authors: M. Messina, S. Barnes
Journal: JNCI Journal of the National Cancer Institute (1991)

Since the initial recognition that diet plays a role in the etiology of certain cancers, particularly cancers of the breast and colon, considerable progress has been made in identifying dietary patterns associated with cancer risk. There is general agreement that a high-fat, low-fiber diet, like that consumed by much of the industrialized world, increases cancer risk and that plant-based diets, rich in whole grains, legumes, and fruits and vegetables, are protective. It has been, however, considerably more difficult to identify specific foods, types of food, or components of foods that influence cancer risk. The recent workshop on The Role of Soy Products in Cancer Prevention, sponsored by the National Cancer Institute, had two objectives: I) to evaluate the role of soybeans, food products derived from soybeans, and specific components of soybeans in the dietary prevention of cancer and 2) to recommend research initiatives and approaches for further studies of the effect of soy intake on human cancer risk. The meeting was chaired by Stephen Barnes and organized by Mark Messina.
Coitus and the Fetus
Authors: Arthur L. Herbst
Journal: New England Journal of Medicine (1979)

IN this issue Naeye describes an association between coitus and amniotic-fluid infection that resulted in increased fetal morbidity and mortality. The findings are based on a study of 26,886 single-born infants delivered between 1959 and 1966 as part of the Collaborative Perinatal Project conducted at 12 medical centers. The diagnosis of mild amniotic-fluid infection was made if more than four neutrophils per microscopical high-power field were found in the subchorionic plate of the placenta. Severe infection was diagnosed if there were more than 15 neutrophils. Placental inflammation and perinatal mortality were more frequently observed if coitus was reported to have . . .
The Role of Intravenous Amiodarone in the Management of Cardiac Arrhythmias
Authors: Aseem D. Desai
Journal: Annals of Internal Medicine (1997)

Purpose: To review the electropharmacology, clinical applications, side effects, and hemodynamic profile of intravenous amiodarone. Data Sources: The MEDLINE database was searched for English-language material, including reports of clinical trials and in vivo studies, review articles, and abstracts presented at national symposia, that was published between 1985 and 1996. Bibliographies of textbooks and articles were also examined. Study Selection: Studies that reported on the efficacy, toxicity, and hemodynamic profile of intravenous amiodarone and studies that examined the pharmacologic behavior of intravenous amiodarone in laboratory models were reviewed. Data Extraction: Study design and quality and relevant data on efficacy of suppression and treatment of arrhythmias with oral and intravenous amiodarone therapy, the reported mechanisms of antiarrhythmic effect, and hemodynamic changes seen with therapy were analyzed. Data Synthesis: Amiodarone is a unique antiarrhythmic agent that is now available in oral and intravenous forms in the United States. The use of intravenous amiodarone in the short-term treatment of life-threatening or hemodynamically unstable rhythm disturbances has generated much interest. Amiodarone has many electropharmacologic actions, some of which differ between the oral and intravenous forms. The wide clinical application of amiodarone includes treatment and prevention of supraventricular and ventricular arrhythmias and arrhythmias related to myocardial infarction. Intravenous amiodarone is effective for supraventricular and ventricular arrhythmias that are resistant to other antiarrhythmic agents. The effectiveness of intravenous amiodarone as short-term treatment also suggests that the drug has an important role in protocols of advanced cardiac life support. Intravenous amiodarone seems to have an overall favorable hemodynamic profile and does not produce many of the unwanted long-term side effects associated with oral therapy. Conclusion: Intravenous amiodarone shows much promise for the short-term treatment of unstable arrhythmias. Its favorable hemodynamic effects and minimal short-term side effects make it an attractive option in the management of cardiac arrhythmias.
TRANSAMINATION IN THE METABOLISM OF ß-2-THIENYL-DL-ALANINE IN NORMAL AND NEOPLASTIC CELLS IN VITRO
Authors: John A. Jacquez, Ralph K. Barclay, C. Chester Stock
Journal: The Journal of Experimental Medicine (1952)

In tissue cultures of C-57 black mouse heart and sarcoma T-241, beta-2-thienyl-DL-alanine acts specifically as a phenylalanine antagonist. Heart cultures can transaminate between beta-2-thienyl-DL-alanine and phenylpyruvate to form L-phenylalanine and thus block the toxic action of the remaining beta-2-thienyl-DL-alanine, whereas sarcoma T-241 cultures cannot. Of eleven mouse tumors and four rat tumors tested for their ability to perform this reaction, nine tumors had little or no activity. The beta-2-thienylpyruvic acid resulting from transamination further reacts to form a red compound the exact structure of which is not yet known.