tbuckley/cabot-search huggingface dataset:
Pancreatic enzyme response to a liquid meal and to hormonal stimulation. Correlation with plasma secretin and cholecystokinin levels.
Authors: C Beglinger, M Fried, I Whitehouse, J B Jansen, C B Lamers, K Gyr
Journal: Journal of Clinical Investigation (1985)

Pancreatic trypsin output and plasma secretin and cholecystokinin (CCK) levels were measured in five healthy volunteers to investigate the mechanisms involved in regulating postprandial pancreatic secretion. The pancreas was stimulated by a liquid test meal or by either intravenous secretin (1-82 pmol/kg-1 per h-1) or caerulein, a CCK analogue (2.3-37 pmol/kg-1 per h-1), or by a combination of secretin and caerulein. Pancreatic secretion was assessed by a marker perfusion technique (polyethylene glycol [PEG 4000]), plasma secretin, and CCK by specific radioimmunoassays. Increasing doses of secretin produced increasing bicarbonate output (P less than 0.01), whereas trypsin was not stimulated over basal. Graded caerulein produced a stepwise increase in trypsin and bicarbonate output (P less than 0.01). Potentiation occurred for bicarbonate secretion between secretin and caerulein, but not for trypsin output. Postprandial trypsin secretion averaged 29.1 IU/min-1 over 150 min (equal to 55% of maximal response to caerulein). The peak trypsin response amounted to 90% of maximal caerulein. Significant increases of plasma secretion (P less than 0.05) and CCK (P less than 0.01) were observed after the meal. Comparison of enzyme and CCK responses to the testmeal or to exogenous caerulein suggested that the amount of CCK released after the meal could account for the postprandial trypsin secretion. We conclude that (a) the postprandial enzyme response in man is submaximal in comparison to maximal exogenous hormone stimulation; (b) CCK is a major stimulatory mechanism of postprandial trypsin secretion, whereas secretin is not involved; and (c) Potentiation of enzyme secretion is not a regulatory mechanism of the postprandial secretory response.
Fate of Registrars in the South-Western Region
Authors: A. G. Riddell, A. M. Elliott
Journal: BMJ (1970)

The fate of registrars in general surgery in the South-Western Region has been surveyed. Once a man has taken a registrarship in general surgery he is largely committed to surgery as a career. Consequently, if he fails to obtain promotion in the Health Service he emigrates, and as a result about 37% of British graduates who become surgical registrars eventually settle abroad.
Acute HIV Infection Presenting With Painful Swallowing and Esophageal Ulcers
Authors: Linda Rabeneck
Journal: JAMA (1990)

We describe an acute human immunodeficiency virus (HIV) infection in 16 homosexual men who presented with painful swallowing (odynophagia). Eleven men had a maculopapular rash and 3 had palatal ulcers. At esophagogastroduodenoscopy (endoscopy), multiple discrete esophageal ulcers measuring 0.3 to 1.5 cm in diameter were observed. Electron microscopy of biopsy specimens taken from the ulcer margins in 8 men revealed viral particles 120 to 160 nm in diameter whose morphologic characteristics were those of retroviruses. Human immunodeficiency virus seroconversion was documented in 15 men by Western blot analysis. In 3 men, HIV-1 was isolated from peripheral blood mononuclear cells, in 2 men HIV-1 was isolated from peripheral blood monocytes, and in 1 man HIV-1 was isolated from tissue taken from the margins of the esophageal ulcers. These observations extend our knowledge of the clinical spectrum of acute HIV infection syndromes and suggest that cells in the esophagus are a target for HIV-1 infection. (<i>JAMA</i>. 1990;263:2318-2322)
Panautonomic Dysfunction and Guillain-Barré Syndrome-Reply
Authors: Michael I. Weintraub
Journal: JAMA (1980)

<h3>In Reply.—</h3> The report by Levy contains several statements that require clarification. Autonomic dysfunction in Guillain-Barré syndrome is extremely common and plays a significant role in producing mortality. The outcome in any individual case still remains unpredictable and, therefore, there is no substitute for careful clinical observation and monitoring. Since spontaneous fluctuations in blood pressure, heart rate, and sweating have been observed to occur within minutes in the same patient, it is apparent that carefully monitored patients tend to have a better prognosis for survival. One author noted that the mortality from the disease could be reduced from 25% to less than 5% with competent respiratory and cardiac support care units.<sup>1</sup> Sudden vasomotor collapse in the bedridden Guillain-Barré patient poses a diagnostic dilemma to the physician who must consider an acute, massive myocardial infarction, pulmonary embolism, or autonomic collapse. The rationale for considering the use of the Swan-Ganz catheter,
Thrombin-initiated platelet activation in vivo is vWF independent during thrombus formation in a laser injury model
Authors: Christophe Dubois, Laurence Panicot-Dubois, Justin F. Gainor, Barbara C. Furie, Bruce Furie
Journal: Journal of Clinical Investigation (2007)

Adhesion of platelets to an injured vessel wall and platelet activation are critical events in the formation of a thrombus. Of the agonists involved in platelet activation, thrombin, collagen, and vWF are known to induce in vitro calcium mobilization in platelets. Using a calcium-sensitive fluorochrome and digital multichannel intravital microscopy to image unstimulated and stimulated platelets, calcium mobilization was monitored as a reporter of platelet activation (as distinct from platelet accumulation) during thrombus formation in live mice. In the absence of vWF, platelet activation was normal, but platelet adherence and aggregation were attenuated during thrombus formation following laser-induced injury in the cremaster muscle microcirculation. In WT mice treated with lepirudin, platelet activation was blocked, and platelet adherence and aggregation were inhibited. The kinetics of platelet activation and platelet accumulation were similar in FcRgamma(-/-) mice lacking glycoprotein VI (GPVI), GPVI-depleted mice, and WT mice. Our results indicate that the tissue factor-mediated pathway of thrombin generation, but not the collagen-induced GPVI-mediated pathway, is the major pathway leading to platelet activation after laser-induced injury under the conditions employed. In the tissue factor-mediated pathway, vWF plays a role in platelet accumulation during thrombus formation but is not required for platelet activation in vivo.
Indian health ministry challenges report of totally drug resistant tuberculosis
Authors: G. Mudur
Journal: BMJ (2012)

<h3>Abstract</h3> The functions of proteins and RNAs are determined by a myriad of interactions between their constituent residues, but most quantitative models of how molecular phenotype depends on genotype must approximate this by simple additive effects. While recent models have relaxed this constraint to also account for pairwise interactions, these approaches do not provide a tractable path towards modeling higher-order epistasis. Here, we show how latent variable models with nonlinear dependencies can be applied to capture beyond-pairwise constraints in biomolecules. We present a new probabilistic model for sequence families, DeepSequence, that can predict the effects of mutations across a variety of deep mutational scanning experiments significantly better than site independent or pairwise models that are based on the same evolutionary data. The model, learned in an unsupervised manner solely from sequence information, is grounded with biologically motivated priors, reveals latent organization of sequence families, and can be used to extrapolate to new parts of sequence space.
Salmonella Arteritis — Preoperative Diagnosis and Cure of<i>Salmonella typhimurium</i>Aortic Aneurysm
Authors: Richard H. Meade, John M. Moran
Journal: New England Journal of Medicine (1969)

ALL reported cases of salmonella aortitis and aneurysm have with one exception ended fatally despite antibiotic or surgical therapy.1 The diagnosis of aortic aneurysm had been made or suspected in ...
Etiology and pathogenesis of airway disease in children and adults from rural communities.
Authors: D A Schwartz
Journal: Environmental Health Perspectives (1999)

Asthma is the most common chronic disease of childhood and affects nearly 5 million children. The prevalence and severity of childhood asthma have continued to increase over the past decade despite major advances in the recognition and treatment of this condition. A comparison of urban and rural children suggests that the etiology of airway disease is multifactorial and that unique exposures and genetic factors contribute to the development of asthma in both settings. The most important environmental exposure that distinguishes the rural environment and is known to cause asthma is the organic dusts. However, animal-derived proteins, common allergens, and low concentrations of irritants also contribute to the development of airway disease in children and adults living in rural communities. A fundamental unanswered question regarding asthma is why only a minority of children who wheeze at an early age develop persistent airway disease that continues throughout their life. Although genetic factors are important in the development of asthma, recurrent airway inflammation, presumably mediated by environmental exposures, may result in persistent airway hyperresponsiveness and the development of chronic airway disease. Increasing evidence indicates that control of the acute inflammatory response substantially improves airflow and reduces chronic airway remodeling. Reducing exposure to agricultural dusts and treatment with anti-inflammatory medication is indicated in most cases of childhood asthma. In addition, children with asthma from rural (in comparison to urban) America face multiple barriers that adversely affect their health e.g., more poverty, geographic barriers to health care, less health insurance, and poorer access to health care providers. These unique problems must be considered in developing interventions that effectively reduce the morbidity and mortality of asthma in children from rural communities.
Physiology of IgD. IV. Enhancement of antibody production in mice bearing IgD-secreting plasmacytomas.
Authors: B Xue, R Coico, D Wallace, G W Siskind, B Pernis, G J Thorbecke
Journal: The Journal of Experimental Medicine (1984)

Immune responses to trinitrophenylated hemocyanin (TNP-KLH), Ficoll (TNP-Ficoll), and Brucella abortus (TNP-BA) were examined in BALB/c mice bearing subcutaneous transplants of TEPC-1017 and TEPC-1033, the two known IgD-secreting BALB/c plasmacytomas. Both primary and secondary 19S and 7S splenic plaque-forming cell (PFC) responses in spleen to intravenously injected TNP-KLH were enhanced three to fivefold. Primary responses to TNP-Ficoll were 1.5-2 times higher than in control mice (particularly the 7S PFC response). Primary responses to TNP-BA were enhanced by TEPC-1017 but suppressed by TEPC-1033, while secondary responses to TNP-BA were enhanced three to sevenfold by both tumors. Intraperitoneal injections of ascites fluid from mice bearing TEPC-1017 or TEPC-1033, or of IgD isolated from such ascites fluid, caused a similar enhancement of the primary response to TNP-KLH, as did the tumor itself, particularly when injected approximately 1 wk before antigen injection. IgD-containing ascites fluid had no effect on the response of athymic (nu/nu) BALB/c mice to TNP-KLH. These findings suggest the existence of an IgD-responsive immunoregulatory T cell.
Abnormalities of polymorphonuclear leukocyte function associated with a heritable deficiency of high molecular weight surface glycoproteins (GP138): common relationship to diminished cell adherence.
Authors: D C Anderson, F C Schmalstieg, M A Arnaout, S Kohl, M F Tosi, N Dana, G J Buffone, B J Hughes, B R Brinkley, W D Dickey
Journal: Journal of Clinical Investigation (1984)

Investigations of polymorphonuclear leukocyte (PMN) function were performed in a 5-yr-old white female with delayed umbilical cord separation, impaired pus formation, and a severe defect of PMN chemotaxis. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated an almost total deficiency of a high molecular weight glycoprotein(s) (GP138) in the granule and membrane fractions of the patient's cells, and NaB3H4-galactose oxidase labeling demonstrated the absence of a major glycoprotein complex on the surface of her PMNs. Monoclonal antibodies (MAb) were employed in flow cytometry experiments to demonstrate that two previously characterized glycoproteins (Mo1 and LFA1) were undetectable on the surface of the patient's PMNs and monocytes. Immunoprecipitation of 125I-labeled patient cells with subunit specific MAbs confirmed that the alpha-subunits of Mo1 (155 kD) and LFA1 (177 kD) and their common beta-subunit (94 kD) were totally deficient. Functional analyses of patient PMNs demonstrated severe impairment of adherence- and adhesion-dependent cell functions including spreading, aggregation, orientation in chemotactic gradients, antibody-dependent cellular cytotoxicity, and phagocytosis of particles (Oil-Red-0-paraffin, zymosan) selectively opsonized with C3-derived ligands. Patient PMNs demonstrated a normal capacity to rosette with IgG or C3b-coated sheep erythrocytes, but rosette formation with C3bi-coated erythrocytes was profoundly diminished. Adhesion-independent functions including shape change, N-formyl-methionyl-leucyl-3H-phenylalanine binding, and O-2 generation or secretion elicited by soluble stimuli were normal. Membrane fluidity, surface charge, and microtubule assembly were also normal. These findings provide new evidence that critical PMN surface glycoproteins are required to facilitate multiple adhesion-dependent cellular functions of the inflammatory response.
Early and Delayed Consequences of β <sub>2</sub> -Adrenergic Receptor Overexpression in Mouse Hearts
Authors: Stephen B. Liggett, Nicole M. Tepe, John N. Lorenz, Amy M. Canning, Tamara D. Jantz, Sayaka Mitarai, Atsuko Yatani, Gerald W. Dorn
Journal: Circulation (2000)

Background —Transgenic cardiac β 2 -adrenergic receptor (AR) overexpression has resulted in enhanced signaling and cardiac function in mice, whereas relatively low levels of transgenically expressed G αs or β 1 AR have resulted in phenotypes of ventricular failure. Potential relationships between the levels of βAR overexpression and biochemical, molecular, and physiological consequences have not been reported. Methods and Results —We generated transgenic mice expressing β 2 AR at 3690, 7120, 9670, and 23 300 fmol/mg in the heart, representing 60, 100, 150, and 350 times background βAR expression. All lines showed enhanced basal adenylyl cyclase activation but a decrease in forskolin- and NaF-stimulated adenylyl cyclase activities. Mice of the highest-expressing line developed a rapidly progressive fibrotic dilated cardiomyopathy and died of heart failure at 25±1 weeks of age. The 60-fold line exhibited enhanced basal cardiac function without increased mortality when followed for 1 year, whereas 100-fold overexpressors developed a fibrotic cardiomyopathy and heart failure, with death occurring at 41±1 weeks of age. Adenylyl cyclase activation did not correlate with early or delayed decompensation. Propranolol administration reduced baseline +dP/dt max to nontransgenic levels in all β 2 AR transgenics except the 350-fold overexpressors, indicating that spontaneous activation of β 2 AR was present at this level of expression. Conclusions —These data demonstrate that the heart tolerates enhanced contractile function via 60-fold β 2 AR overexpression without detriment for a period of ≥1 year and that higher levels of expression result in either aggressive or delayed cardiomyopathy. The consequences for enhanced βAR function in the heart appear to be highly dependent on which signaling elements are increased and to what extent.
Increased P-wave Dispersion in Patients with New Diagnosed Lichen Planus
Authors: Musa Sahin, Serap Gunes Bilgili, Hakki Simsek, Serkan Akdag, Aytac Akyol, Hasan Ali Gumrukcuoglu, Mehmet Yaman, Yasemin Bayram, Ayse Serap Karadag
Journal: Journal of the American College of Cardiology (2013)
Noninvasive estimation of transmitral pressure drop across the normal mitral valve in humans: importance of convective and inertial forces during left ventricular filling
Authors: Michael S. Firstenberg, Pieter M. Vandervoort, Neil L. Greenberg, Nicholas G. Smedira, Patrick M. McCarthy, Mario J. Garcia, James D. Thomas
Journal: Journal of the American College of Cardiology (2000)
Placental Permeability of Lead
Authors: Stanley J. Carpenter
Journal: Environmental Health Perspectives (1974)

The detection of lead in fetal tissues by chemical analysis has long been accepted as prima facie evidence for the permeability of the placenta to this nonessential trace metal. However, only a few investigations, all on lower mammalian species, have contributed any direct experimental data bearing on this physiological process. Recent radioactive tracer and radioautographic studies on rodents have shown that lead crosses the placental membranes rapidly and in significant amounts even at relatively low maternal blood levels. While it is not possible to extrapolate directly the results of these experiments to humans because of differences in placental structure and other factors, the results do serve as a warning of the possible hazard to the human embryo and fetus of even low levels of lead in the maternal system.
Nature of anaemia in rheumatoid arthritis. X. Folate-releasing properties of plasma in health and disease, with special reference to rheumatoid arthritis.
Authors: A Omer, A G Mowat
Journal: Annals of the Rheumatic Diseases (1969)

The availability of erythrocyte folate in an assay- able form depends on the interaction of a plasma factor with inactive precursors in the red cell (Toennies, Usdin, and Phillips, 1956).Low levels of erythrocyte folate have been reported in cases of megaloblastic erythropoiesis due to either folate or vitamin B12 deficiency (Hansen and Weinfeld, 1962; Cooper and Lowenstein, 1964; Hoffbrand, Newcombe, and Mollin, 1966), and these low levels have been attributed to a lack of erythrocyte folate precursors rather than to a decrease in plasma factor activity.Thus, Cooper and Lowenstein (1964) found no significant alteration in the folate-releasing properties of plasma from two patients with perni- cious anaemia.Similar findings were reported by Hoffbrand and others (1966) in megaloblastic anaemia due to both folate and vitamin B12 defi- ciency.Omer and Mowat (1968), in a study of folate metabolism in patients with rheumatoid arthritis, found sub-normal erythrocyte folate values in fourteen of 37 cases (37 per cent.).It was found that erythrocyte folate release by rheumatoid plasma was significantly reduced compared to the release by control plasma.The present paper reports further investigations undertaken to compare the erythrocyte folate- releasing properties of plasma from patients with rheumatoid arthritis, patients with megaloblastic erythropoiesis due to either folate or vitamin B12 deficiency, and normal controls.
Isolated Granulomas in Hodgkin's Disease
Authors: Marshall E. Kadin, Sarah S. Donaldson, Ronald F. Dorfman
Journal: New England Journal of Medicine (1970)

THE occasional occurrence of a granulomatous process in tissues involved by Hodgkin's disease has long been recognized.1 , 2 However, the presence of noncaseating tubercle-like granulomas within otherwise uninvolved organs of patients with Hodgkin's disease is not well known. To date, only isolated cases of this finding have been reported3 4 5 6 and have been thought by some to represent coexistent sarcoidosis.5 Of great concern to us has been the interpretation of these granulomas as additional foci of Hodgkin's disease in patients referred to this institution.We have encountered this, as yet unexplained, phenomenon in a large number of patients with Hodgkin's disease studied . . .
New Tests for Prostate Cancer May Be Nearing the Clinic
Authors: R. S. Tuma
Journal: JNCI Journal of the National Cancer Institute (2010)

The prostate-specific antigen (PSA) test to detect prostate cancer is notoriously weak on specificity. It not only has a substantial rate of false-positive results, leading to many negative biopsies, but also can lead to overtreatment by detecting non – life-threatening tumors. Improved detection methods, however, are in development and may be nearing the clinic, according to data from recent national meetings.
Primary liver resection and salvage transplantation or primary liver transplantation in patients with single, small hepatocellular carcinoma and preserved liver function: An outcome-oriented decision analysis
Authors: Pietro E. Majno, François P. Sarasin, Gilles Mentha, Antoine Hadengue
Journal: Hepatology (2000)

Two treatments are accepted for patients with solitary hepatocellular carcinoma </=5 cm in size and with preserved hepatic function: (1) liver resection, which can be performed without delay but has a high recurrence rate, and (2) liver transplantation, which has a better long-term survival, but is not easily available because grafts are scarce. A third possibility is to offer liver resection first and liver transplantation for tumor recurrence or deteriorating liver function ("salvage" transplantation). We investigated the implications of such a strategy with a Markov-based decision analytic model. In a scenario assuming intermediate values for 4 main variables (12-month waiting list; tumor progression outside transplantation criteria: 4% per month; recurrence after resection: 20% per year; recurrences eligible for transplantation: 60%), the life expectancy was 8.8 years for primary transplantation versus 7.8 years for primary resection and salvage transplantation, with a calculated use of grafts at 5 years of 52% for primary transplantation versus 23% for salvage transplantation. This study estimates of the survival and graft-saving of a strategy of primary resection and salvage transplantation according to variables that are to some extent predictable. This strategy may be a rational way to cope with lengthening waiting lists, especially for patients with tumors close to the limit for transplantation criteria, if the results of liver resection are good, if patients with the lowest risks of recurrence can be selected, and if a strict follow-up can detect recurrences when the patients are still transplantable.
Arabian nights 1001 tales of how pharmaceutical companies cater to the material needs of doctors: case report
Authors: I. A Giannakakis, J. P A Ioannidis
Journal: BMJ (2000)

To describe how pharmaceutical companies cater to the material needs of doctors.Case report of memoirs.Facilities that have nothing to do with medicine, somewhere in the Arabian peninsula.Random sample of doctors.Promotion by the pharmaceutical industry.Short term outcomes were travel, pleasure, amusement, and gifts, and long term outcomes were the market share of specific companies.Short term outcomes were heterogeneous, underlying the diversity of the means employed by the pharmaceutical industry to subvert, divert, and influence medical practice. Overall, 200 doctors were dressed in white gowns, a doctor in preventive medicine quoted Hippocrates in favour of smoking, a senior doctor became a poet, a doctor trying to understand the Methods section of a poster paper wondered whether he should have been sunbathing at the beach instead, and two women doctors were kidnapped by Bedouin warriors. Long term outcomes on the sales of the company drugs are pending but are likely to be most favourable.Eat, drink, be merry, and boost prescriptions.
Growth arrest–specific protein 1 is a novel endogenous inhibitor of glomerular cell activation and proliferation
Authors: Claudia R.C. van Roeyen, Stephanie Zok, Jessica Pruessmeyer, Peter Boor, Yoshikuni Nagayama, Stefan Fleckenstein, Clemens D. Cohen, Frank Eitner, Hermann-Josef Gröne, Tammo Ostendorf, Andreas Ludwig, Jürgen Floege
Journal: Kidney International (2012)