tbuckley/cabot-search huggingface dataset:
Effects of Exercise on Insulin Sensitivity in Humans
Authors: John T Devlin
Journal: Diabetes Care (1992)

Physical exercise is promoted as one of the primary therapeutic strategies available to increase insulin sensitivity in individuals deemed at risk from insulin resistance and its attendant hyperinsulinism. Subjects with non-insulin-dependent diabetes mellitus (NIDDM) and impaired glucose tolerance (IGT) represent the major clinical population in which physical training is promoted as a treatment modality to improve insulin sensitivity. This manuscript reviews both the acute effects of muscular contractions and the effects of physical training on insulin sensitivity in NIDDM and insulin-dependent diabetic (IDDM) human subjects. Additionally, the effects of localized (regional) muscular contractions on insulin-mediated glucose disposal in previously exercised and nonexercised muscle groups will be discussed briefly.
Effects of novel retinoic acid metabolism blocking agent (VN/14-1) on N-methyl-N-nitrosourea (MNU)-induced mammary carcinoma and uterus in the rat model.
Authors: PE Goss, VC Njar, S Qi, H Hu, LK Gediya, P Puranik, A Khandelwal
Journal: Cancer Research (2009)

Abstract Abstract #2133 Background: All-trans-retinoic acid (ATRA) and other retinoids play key roles in prevention and therapy of many proliferative diseases including cancers. VN/14-1 [4-(±)-(1H-Imidazol-1-yl)-(E)-retinoic acid], which is a new generation novel retinoic acid metabolism blocking agent (RAMBA), works by inhibiting the breakdown of ATRA. The inhibitory effects of VN/14-1 on the growth of human breast cancer cells and human breast tumors in the nude mouse model have been previously demonstrated. The purpose of this study was to evaluate the effects of VN/14-1 on the N-methyl-N-nitrosourea (MNU)-induced rat mammary carcinoma model, as well as on the uterus in immature ovariectomized (OVX) rats.&amp;#x2028; Methods: (1) VN/14-1 (5, 10, and 20 mg/kg/d) was given by oral gavage to grouped female Sprague Dawley (SD) rats bearing MNU-induced mammary carcinoma for 8 weeks, after which tumor weight and volume, as well as histology were measured. (2) VN/14-1 (10 and 20 mg/kg/d) and b-estradiol (10 mg/kg/d) were given alone or in combination, by oral gavage (VN/14-1) and subcutaneous injection (b-estradiol), to immature OVX SD rats for 3 days, after which uterine weight and histology were measured.&amp;#x2028; Results: (1) At the end of the treatment period, the administration of 5, 10 and 20 mg/kg/d VN/14-1 caused significant reductions of 19.1, 34.4 and 44.3%, respectively, in mean tumor weight compared with the control animals (all p &amp;lt; 0.05). The cumulative tumor growth was also significantly slower in groups receiving 5, 10 and 20 mg/kg/d compared to the control group in a dose-dependent manner. (2) Immature OVX rats given VN/14-1 at doses of 10 and 20 mg/kg, had reduction in uterine wet weight of up to 56% compared to OVX controls (P &amp;lt; 0.001). OVX rats given VN/14-1 of 10 and 20 mg/kg in combination with β-estradiol had reduction in uterine wet weight of up to 58% compared to the OVX rats given β-estradiol alone (P &amp;lt; 0.001). The adverse toxic effects such as fatigue and anorexia were occurred in the groups at high dose of 20 mg/kg.&amp;#x2028; Conclusions: RAMBA VN/14-1 was able to inhibit the growth of tumors in the MNU-induced ER positive rat mammary tumor model and antagonized the stimulatory effect of β-estradiol on the uterus. The studies suggest VN/14-1 might be an effective novel therapy for ER positive breast cancer. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2133.
Clubbing of the Fingers In Sarcoidosis
Authors: Janelle Yancey
Journal: JAMA (1972)

<h3>To the Editor.—</h3> Clubbing of the fingers occurs frequently in a wide variety of unrelated cardiopulmonary disorders including bronchiectasis, lung abscess, bronchial carcinoma, congenital heart disease, arteriovenous aneurysm, and interstitial fibrosis. It occurs less frequently in ulcerative colitis, liver disease, bacterial endocarditis, and carcinoma of esophagus and stomach.<sup>1</sup>Clubbing has not been reported in sarcoidosis.<sup>2</sup> Of 136 patients with histologically proven sarcoidosis followed-up at Los Angeles County—University of Southern California, we have recently studied four who also had marked clubbing of the fingers: two patients had clubbing at the time of initial presentation and the other two developed clubbing during the follow-up period. All four patients had radiological evidence of bilateral interstitial disease (Table). Finger clubbing is a common feature with an incidence of 70% to 90% of patients having fibrosing alveolitis [diffuse interstitial fibrosis, (DIF)].<sup>3,4</sup>Patients with sarcoidosis may present with radiological features that are indistinguishable
Pulmonary Embolism and Unexpected Death in Supposedly Normal Persons
Authors: R. T. Breckenridge, O. D. Ratnoff
Journal: New England Journal of Medicine (1964)

SEVERAL authors have called attention to the occurrence of phlebothrombosis and pulmonary embolism in apparently healthy people.1 2 3 4 5 6 How frequently death occurs unexpectedly from pulmonary embolism arising from phlebothrombosis in normal persons is unknown. To estimate the minimal incidence of such deaths, the experience of the coroner's office of a large metropolitan county was reviewed.MethodsCases in which unexpected death was attributed to pulmonary emboli were selected from the autopsy records of the coroner's office of Cuyahoga County, Ohio. This survey, encompassing the period from January 1, 1951, through August 1, 1962, was restricted to persons of both sexes between . . .
Interleukin 1 beta propeptide is detected intracellularly and extracellularly when human monocytes are stimulated with LPS in vitro.
Authors: G C Higgins, J L Foster, A E Postlethwaite
Journal: The Journal of Experimental Medicine (1994)

Human interleukin 1 beta (IL-1 beta) is synthesized as an inactive precursor that is cleaved by IL-1 converting enzyme (ICE) between Asp116 and Ala117 to form COOH-terminal mature IL-1 beta and NH2-terminal IL-1 beta propeptide. Little is known about the fate of the NH2-terminal cleavage product. In this study, human recombinant (hr)IL-1 beta propeptide (amino acids 2-116) was produced and used to prepare specific antibodies which do not recognize mature human IL-1 beta. These anti-propeptide antibodies were used for immunoprecipitation of biosynthetically labeled proteins from lipopolysaccharide-stimulated human monocytes. Analysis of immunoprecipitates by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography revealed that these antibodies recognize precursor IL-1 beta and two unique proteins: one migrating at 17.5 kD and one at 14 kD. The larger of these two proteins has a migration nearly identical to that of the recombinant IL-1 beta propeptide, and most likely represents naturally derived propeptide. The protein migrating at 14 kD may result from a second cleavage by ICE, between Asp27 and Gly28. These proteins accumulate intracellularly and extracellularly during pulse-chase experiments, and therefore represent stable products of precursor IL-1 beta cleavage.
Preventing falls in elderly people living in hospitals and care homes
Authors: Ian D Cameron, Susan Kurrle
Journal: BMJ (2007)

Incident reporting should ideally communicate all information relevant to patient safety.Local incident reporting systems in hospitals typically use an incident form that comprises basic clinical details and a brief description of the incident.Such systems are ideally used as part of an overall safety and quality improvement strategy, but in practice they may be dominated by managing claims and complaints. 1 Specialty reporting systems 2 and large scale systems, such as that of the UK National Patient Safety Agency (www.npsa.nhs.uk/),allow wider dissemina-
Relationship between skin type and erythemal response to anthralin
Authors: P.D.L. MAURICE, M.W. GREAVES
Journal: British Journal of Dermatology (1983)

Anthralin erythema dose-response curves were drawn for thirty adult patients of various skin types who had chronic plaque psoriasis. A small statistically significant difference was observed between the curves for skin types I and IV but this was not thought to be sufficient to account for the clinical impression of increased anthralin irritancy in fair-skinned subjects.
TCT-816 Transcatheter Orthotopic Aortic Valve Implantation In Sheep: Chronic Survival And Valve Performance Evaluation
Authors: Jeannot Potvin, Keith D. Dawkins, Dominic J. Allocco, Amelie Bouchard, Robert Chang, Barbara Huibregtse, Lise Lachance, Guy LeClerc
Journal: Journal of the American College of Cardiology (2013)
Improving peer review: who's responsible?
Authors: Frank Davidoff
Journal: BMJ (2004)

Peer review needs recognition at every stage of scientific life 

Peer review matters. Why? Firstly, scientific assertions can't be proved; they can only be disproved. The doubts raised by peer reviewers are therefore a crucial element in scientific reasoning.More specifically, as Francis Bacon put it in 1605, the “registering and posting of doubts has a double use:” it not only guards us “against errors,” but also furthers the process of inquiry, causing issues that would otherwise be “passed by lightly without intervention” to be “attentively and carefully observed.” Moreover, since scientific findings effectively don't exist until they're in written form, the doubts raised during editorial peer review come at a particularly crucial step in the overall scientific process.1 Secondly, the exchange of information for professional recognition is the principal instrument of social control within the scientific community.2 Approval by peer review is perhaps the single most powerful expression of that recognition. Thirdly, and more pragmatically, journal editors depend heavily on peer review to accomplish their two main tasks—selecting papers and improving their quality1 3—even though editors themselves are apparently the source of substantive improvements to manuscripts more often than either peer reviewers or statisticians. …
MEMORIAL TO MR. ETHERINGTON-SMITH
Authors: A. A. Bowlby, W. B. Close, G. A. Davis, J. H. Gibbon, H. Gold, W. P. Herringham, R. C. Lehmann, H. Marsh, S. D. Muttlebury, G. Nickalls, G. D. Rowe, H. T. Steward
Journal: BMJ (1913)
The Natural History of Calcium Urolithiasis
Authors: Fredic L. Coe
Journal: JAMA (1977)

The course of untreated calcium renal stones, derived from the retrospective study of 300 patients with defined metabolic disorders and from the analysis of two prospective, published studies, is complex and heterogeneous. Generally, stones provoke considerable morbidity; hyperuricosuria is associated with an unusually severe stone disease. Stone recurrence rates usually remain stable, or rise with successive stones; in a minority of patients, the reverse is true. A single stone is likely to be followed by a recurrence. The mean time to recurrence averages 6.78 years, with peaks at 1.56 and eight years. Because the disease is likely to be morbid and chronic and does not wane with age, diagnostic evaluation and treatment should be strongly considered for any patient with recurrent stones, and for those in whom recurrence is likely to pose more than the usual risk. (<i>JAMA</i>238:1519-1523, 1977)
Chloramphenicol Toxicity
Authors: Loren M. Rosenbach, Alendry P. Caviles, W. J. Mitus
Journal: New England Journal of Medicine (1960)

SINCE the isolation of chloramphenicol from Streptomyces venezuelae in 1947 and its introduction into clinical use in 1948, numerous cases of untoward hematologic effects have been recorded. Animal trials and early clinical use apparently indicated no dangerous side effects although, in 1949, Smadel1 made what has become an often quoted statement: "The presence of the nitrobenzene radical in the structure of chloramphenicol led to the suspicion that the drug might be toxic for the hematopoietic system." Indeed, in 1950 the first reported case of aplastic anemia in association with chloramphenicol therapy appeared,2 and in 1952 some ten papers reported a . . .
Influence of Isoproterenol and Ouabain on Excitation-Contraction Coupling, Cross-Bridge Function, and Energetics in Failing Human Myocardium
Authors: Gerd Hasenfuss, Louis A. Mulieri, Paul D. Allen, H. Just, N.R. Alpert
Journal: Circulation (1996)

In patients with heart failure, long-term treatment with catecholamines and phosphodiesterase inhibitors, both of which increase cyclic AMP levels, may be associated with increased mortality, whereas mortality may not be increased with glycoside treatment. Differences in clinical benefit between cyclic AMP-dependent inotropic agents and cardiac glycosides may be related to differences of these drugs on calcium cycling and myocardial energetics.Isometric heat and force measurements were used to investigate the effects of isoproterenol and ouabain on myocardial performance, cross-bridge function, excitation-contraction coupling, and energetics in myocardium from end-stage failing human hearts. Isoproterenol (1 mumol/L) increased peak twitch tension by 55% and decreased time to peak tension and relaxation time by 30% and 26%, respectively (P < .005). Ouabain (0.38 +/- 0.11 mumol/L) increased peak twitch tension and relaxation time by 41% and 20%, respectively, and decreased time to peak tension by 12% (P < .05). With isoproterenol, the amount of excitation-contraction coupling-related heat evolution (tension-independent heat) increased by 246% (P < .05) and the economy of excitation-contraction coupling decreased by 61% (P < .05). Ouabain increased tension-independent heat by only 61% (P < .05) and did not significantly influence economy of excitation-contraction coupling. The effects of isoproterenol on excitation-contraction coupling resulted in a 21% (P < .005) decrease of overall contraction economy, which was not significantly changed with ouabain. Neither isoproterenol nor ouabain influenced energetics of cross-bridge cycling or recovery metabolism.Major differences between the effects of isoproterenol and ouabain in failing human myocardium are related to calcium cycling with secondary effects on myocardial energetics.
Characterisation of size and direction of osteophyte in knee osteoarthritis: a radiographic study
Authors: Y Nagaosa
Journal: Annals of the Rheumatic Diseases (2002)

Objectives: To examine the size and direction of osteophyte in knee osteoarthritis (OA) and to determine associations between osteophyte size and other radiographic features. Methods: Knee radiographs (standing extended anteroposterior and 30 degrees flexion skyline views) were examined from 204 patients referred to hospital with symptomatic knee OA (155 women, 49 men; mean age 70, range 34–91 years). A single observer assessed films for osteophyte size and direction at eight sites; narrowing in each compartment; varus/valgus angulation; patellofemoral subluxation; attrition; and chondrocalcinosis using a standard atlas, direct measurement, or visual assessment. For analysis, one OA knee was selected at random from each subject. Results: Osteophyte direction at the eight sites was divisible into five categories. At all sites, except for the lateral tibial plateau and the medial patella, osteophyte direction varied according to (<i>a</i>) the size of osteophyte and (<i>b</i>) the degree of local narrowing. At the medial femur, medial tibia, and lateral femur osteophyte direction changed from being predominantly horizontal to predominantly vertical with increasing size. The size of osteophyte correlated positively with the severity of local narrowing, except for the medial patellofemoral compartment where osteophyte size correlated positively with the severity of narrowing in the medial tibiofemoral compartment. Logistic regression analysis showed that osteophyte size was associated not only with local narrowing but also with local malalignment and bone attrition, and that chondrocalcinosis was positively associated with osteophyte size at multiple sites. Conclusion: In patients referred to hospital with knee OA different patterns of osteophyte direction are discernible. Osteophyte size is associated with local compartmental narrowing but also local alignment and attrition. Chondrocalcinosis is associated with osteophytosis throughout the joint. These data suggest that both local biomechanical and constitutional factors influence the size and direction of osteophyte formation in knee OA.
Mmp23b promotes liver development and hepatocyte proliferation through the tumor necrosis factor pathway in zebrafish
Authors: Fei Qi, Jianbo Song, Hanshuo Yang, Wei Gao, Ning-ai Liu, Bo Zhang, Shuo Lin
Journal: Hepatology (2010)

The matrix metalloproteinase (MMP) family of proteins degrades extracellular matrix (ECM) components as well as processes cytokines and growth factors. MMPs are involved in regulating ECM homeostasis in both normal physiology and disease pathophysiology. Here we report the critical roles of mmp23b in normal zebrafish liver development. Mmp23b was initially identified as a gene linked to the genomic locus of an enhancer trap transgenic zebrafish line in which green fluorescent protein (GFP) expression was restricted to the developing liver. Follow-up analysis of mmp23b messenger RNA (mRNA) expression confirmed its liver-specific expression pattern. Morpholino knockdown of mmp23b resulted in defective hepatocyte proliferation, causing a reduction in liver size while maintaining relatively normal pancreas and gut development. Genetically, we showed that mmp23b functions through the tumor necrosis factor (TNF) signaling pathway. Antisense knockdown of tnfa or tnfb in zebrafish caused similar reductions of liver size, whereas overexpression of tnfa or tnfb rescued liver defects in mmp23b morphants but not vice versa. Biochemically, MMP23B, the human ortholog of Mmp23b, directly interacts with TNF and mediates its release from the cell membrane in a cell culture system. Because mmp23b/MMP23B is highly conserved, our findings in zebrafish warrant further investigation of its role in regulating liver development in mammals.
127. Intraarticular Gene Transfer of Rat TNFR:Fc Suppressed CIA Arthritis
Authors: Ai Zhi Zhao, Kai Gao, Xiao Yan Dong, Jian Qiang Peng, Xiao Bing Wu
Journal: Molecular Therapy (2005)

Tumor necrosis factor |[alpha]| (TNF|[alpha]|) plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA). Systemic administration of ENBREL (an antagonist of TNF|[alpha]|, i.e., TNF receptor-immunoglobulin Fc fusion protein) has been shown to ameliorate joint symptoms in RA patients. In the our study, a collagen induced rat arthritis (CIA) model was used to evaluate the effect of local (intraarticular) or systemic (intramuscular) transfer of TNF receptor-immunoglobulin Fc (TNFR:Fc) fusion gene by AAV2 vector on development and severity of arthritis. 5|[times]|1010v.g. rAAV2/ratTNFR:Fc delivered locally or 8|[times]|1011v.g. delivered systemically resulted in strong suppression of the arthritis as reflected in decreased articular index, inflammatory cell infiltration and cartilage destruction. Administration of the rAAV2/ratTNFR:Fc in one joint also suppressed arthritis in the contralateral joint. TNFR levels in serum were not higher than normal rat in local administration and 2-3 folds higher in systemic administration. Therefore, intraarticular administration could relieve the arthritis with significant lower systemic distribution of TNFR:Fc, which may be a promising approach for antiarthritis therapy.
Carcinogenic Cr(VI) and the Nutritional Supplement Cr(III) Induce DNA Deletions in Yeast and Mice
Authors: Zhanna Kirpnick-Sobol, Ramune Reliene, Robert H. Schiestl
Journal: Cancer Research (2006)

Abstract Industrial Cr(VI) emissions contaminate drinking water sources across the U.S., and many people take Cr(III) nutritional supplements. Cr(VI) is a human pulmonary carcinogen, but whether it is carcinogenic in the drinking water is not known. Due to widespread human exposure, it is imperative to determine the carcinogenic potential of Cr(VI) and Cr(III). DNA deletions and other genome rearrangements are involved in carcinogenesis. We determined the effects of Cr(VI) as potassium dichromate and Cr(III) as chromium(III) chloride on the frequencies of DNA deletions measured with the deletion assay in Saccharomyces cerevisiae and the in vivo pun reversion assay in C57BL/6J pun/pun mice. Exposing yeast and mice via drinking water to Cr(VI) and Cr(III) significantly increased the frequency of DNA deletions. We quantified intracellular chromium concentrations in yeast and tissue chromium concentrations in mice after exposure. Surprisingly, this revealed that Cr(III) is a more potent inducer of DNA deletions than Cr(VI) once Cr(III) is absorbed. This study concludes that both the environmental contaminant Cr(VI) and the nutritional supplement Cr(III) increase DNA deletions in vitro and in vivo, when ingested via drinking water. (Cancer Res 2006; 66(7): 3480-4)
Dynamic Evolution of Immune System Regulators: The History of the Interferon Regulatory Factor Family
Authors: J. Nehyba, R. Hrdlickova, H. R. Bose
Journal: Molecular Biology and Evolution (2009)

This manuscript presents the first extensive phylogenetics analysis of a key family of immune regulators, the interferon regulatory factor (IRF) family. The IRF family encodes transcription factors that play important roles in immune defense, stress responses, reproduction, development, and carcinogenesis. Several times during their evolution, the IRF genes have undergone expansion and diversification. These genes were also completely lost on two separate occasions in large groups of metazoans. The origin of the IRF family coincides with the appearance of multicellularity in animals. IRF genes are present in all principal metazoan groups, including sea sponges, placozoans, comb jellies, cnidarians, and bilaterians. Although the number of IRF family members does not exceed two in sponges and placozoans, this number reached five in cnidarians. At least four additional independent expansions lead up to 11 members in different groups of bilaterians. In contrast, the IRF genes either disappeared or mutated beyond recognition in roundworms and insects, the two groups that include most of the metazoan species. The IRF family separated very early into two branches ultimately leading to vertebrate IRF1 and IRF4 supergroups (SGs). Genes encoding the IRF-SGs are present in all bilaterians and cnidarians. The evolution of vertebrate IRF family members further proceeded with at least two additional steps. First, close to the appearance of the first vertebrate, the IRF family probably expanded to four family members, predecessors of the four vertebrate IRF groups (IRF1, 3, 4, 5 groups). In the second step, 10 vertebrate family members evolved from these four genes, likely as a result of the 2-fold duplication of the entire genome. Interestingly, the IRF family coevolved with the Rel/NF-κB family with which it shares some important evolutionary characteristics, including roles in defense responses, metazoan specificity, extensive diversification in vertebrates, and elimination of all family members in nematodes.