tbuckley/cabot-search huggingface dataset:
Myosin light chain kinase in microvascular endothelial barrier function
Authors: Q. Shen, R. R. Rigor, C. D. Pivetti, M. H. Wu, S. Y. Yuan
Journal: Cardiovascular Research (2010)

Microvascular barrier dysfunction is implicated in the initiation and progression of inflammation, posttraumatic complications, sepsis, ischaemia–reperfusion injury, atherosclerosis, and diabetes. Under physiological conditions, a precise equilibrium between endothelial cell–cell adhesion and actin–myosin-based centripetal tension tightly controls the semi-permeability of microvascular barriers. Myosin light chain kinase (MLCK) plays an important role in maintaining the equilibrium by phosphorylating myosin light chain (MLC), thereby inducing actomyosin contractility and weakening endothelial cell–cell adhesion. MLCK is activated by numerous physiological factors and inflammatory or angiogenic mediators, causing vascular hyperpermeability. In this review, we discuss experimental evidence supporting the crucial role of MLCK in the hyperpermeability response to key cell signalling events during inflammation. At the cellular level, in vitro studies of cultured endothelial monolayers treated with MLCK inhibitors or transfected with specific inhibiting peptides have demonstrated that induction of endothelial MLCK activity is necessary for hyperpermeability. Ex vivo studies of live microvessels, enabled by development of the isolated, perfused venule method, support the importance of MLCK in endothelial permeability regulation in an environment that more closely resembles in vivo tissues. Finally, the role of MLCK in vascular hyperpermeability has been confirmed with in vivo studies of animal disease models and the use of transgenic MLCK210 knockout mice. These approaches provide a more complete view of the role of MLCK in vascular barrier dysfunction.
Shocked by attitude to MRSA
Authors: W. Beaumont
Journal: BMJ (2003)

EDITOR—I am writing with reference to the correspondence from Howard et al.1 My husband was in a NHS hospital for six months in 1999-2000. Visiting each day, I was afraid that the very bad standards of cleanliness and hygiene would result in his suffering an infection on top of heart disease and a stroke, quite enough for him to bear. More by luck than proper standards he did not become infected. Since …
A family with a high incidence of juvenile rheumatoid arthritis.
Authors: Y Yodfat, Z Yossipovitch, I Cohen, E Shapira
Journal: Annals of the Rheumatic Diseases (1972)

The aetiology of juvenile rheumatoid arthritis (JRA) is unknown.All epidemiological attempts to prove a genetic background or familial predisposition were inconclusive.The three recent studies of monozygotic twins (Baum and Fink, 1968; Meyerowitz, Jacox, and Hess, 1968; Kapusta, Metrakos, Pinsky, Shugar, and Naimark, 1969), give little support for any significant genetic predisposition.According to Toumbis, Franklin, McEwen, and Kuttner (1963), serological tests showed a high prevalence of the rheumatoid factor in one pedigree.
Combined Integrin Phosphoproteomic Analyses and Small Interfering RNA–Based Functional Screening Identify Key Regulators for Cancer Cell Adhesion and Migration
Authors: Yanling Chen, Bingwen Lu, Qingkai Yang, Colleen Fearns, John R. Yates, Jiing-Dwan Lee
Journal: Cancer Research (2009)

Abstract Integrins interact with extracellular matrix (ECM) and deliver intracellular signaling for cell proliferation, survival, and motility. During tumor metastasis, integrin-mediated cell adhesion to and migration on the ECM proteins are required for cancer cell survival and adaptation to the new microenvironment. Using stable isotope labeling by amino acids in cell culture–mass spectrometry, we profiled the phosphoproteomic changes induced by the interactions of cell integrins with type I collagen, the most common ECM substratum. Integrin-ECM interactions modulate phosphorylation of 517 serine, threonine, or tyrosine residues in 513 peptides, corresponding to 357 proteins. Among these proteins, 33 key signaling mediators with kinase or phosphatase activity were subjected to small interfering RNA–based functional screening. Three integrin-regulated kinases, DBF4, PAK2, and GRK6, were identified for their critical role in cell adhesion and migration possibly through their regulation of actin cytoskeleton arrangement. Altogether, we not only depict an integrin-modulated phosphorylation network during cell-ECM protein interactions but also reveal novel regulators for cell adhesion and migration. [Cancer Res 2009;69(8):3713–20]
Treatment of severe aplastic anaemia with antilymphocyte globulin or bone-marrow transplantation.
Authors: B Speck, A Gratwohl, C Nissen, U Leibundgut, D Ruggero, B Osterwalder, H P Burri, P Cornu, M Jeannet
Journal: BMJ (1981)

Fifty-three patients with severe aplastic anaemia were admitted to this hospital between January 1976 and June 1980, of whom three arrived in terminal condition and died before treatment for their basic disease could be given. Thus 50 patients were treated and evaluated in a prospective study according to one protocol. Eighteen patients with an HLA-identical sibling underwent bone-marrow transplantation with the aim of achieving haematopoietic chimerism. Thirty-two patients without an HLA-identical sibling were given antilymphocyte globulin with or without an infusion of HLA-haplotype-identical marrow. All these 32 patients received low-dose androgens after the procedure. In the first group eight patients (44%) survived. In the two other groups, 22 patients survived (69%), of whom 20 were completely self-sustaining (63%). Engraftment and graft-versus-host disease did not occur in the group who received antilymphocyte globulin and haploidentical marrow, and the haematopoietic reconstitutions in these patients were all autologous. These results confirm the efficacy of antilymphocyte globulin in the treatment of severe aplastic anaemia and show that such treatment is at least as good as bone-marrow transplantation. Its mechanism of action remains unknown, but most patients with aplastic anaemia have a pool of haematopoietic stem cells able to repopulate the marrow after this type of treatment.
Richard Douglas Jack
Authors: P. Adams
Journal: BMJ (2006)

Medical researcher who pioneered the controlled clinical trial as a gold standard and who demonstrated the efficacy of streptomycin as a treatment for tuberculosisIn a long career-he lived to 106 and worked until he was 102-Philip D'Arcy Hart showed that pneumoconiosis was an industrial disease for which sufferers should receive compensation.In a landmark controlled clinical trial with Sir Austin Bradford Hill, Hart showed that streptomycin, then newly discovered, cured tuberculosis.In 1965 he was made a CBE for this work.He did other major epidemiology, retired at 65, and spent the next 37 years making fundamental advances on the pathogenesis of tubercle bacilli.
Hereditary Angioedema: the Clinical Syndrome and Its Management
Authors: Michael M. Frank, Jeffrey A. Gelfand, John P. Atkinson
Journal: Annals of Internal Medicine (1976)

Hereditary angioedema is manifested by attacks of swelling of the extremities, face, trunk, airway, or abdominal viscera, occurring spontaneously or secondary to trauma. It is inherited as an autosomal dominant trait and is due to deficient activity of the inhibitor of the activated first component of complement. The clinical diagnosis can be confirmed by the findings of low levels of C4 or C1 esterase inhibitor activity, or both. Therapy may be divided into three phases: long-term prophylaxis of attacks, short-term prophylaxis of attacks, and treatment of acute attacks. Long-term prophylaxis may be achieved with antifibrinolytic agents and androgens. Short-term prophylaxis with these agents and plasma transfusions has been successful. Specific therapy for acute attacks is not available, but good supportive care, together with a knowledge of the course of the disease, can prevent asphyxiation from airway obstruction. Before the advent of therapy, mortality was reported as high as 30%.
<i>Mycobacterium tuberculosis</i> Infection after Travel to or Contact with Visitors from Countries with a High Prevalence of Tuberculosis
Authors: MARK N. LOBATO, PHILIP C. HOPEWELL
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

To assess whether there is increased risk of tuberculous infection in children who traveled to or had a household visitor from a country having a high prevalence of tuberculosis, we conducted a case-control study. Children younger than 6 yr of age who had a tuberculin skin test read at public health clinics in areas of California that have a high prevalence of tuberculosis were enrolled. Of the 953 children who had a skin test read, 72 (7.6%) had a positive reaction. By multiple logistic regression analysis, children who had traveled in the 12 mo before the skin test were 3.9 times more likely to have a positive skin test than were children who had not traveled (95% confidence interval [CI], 1.9 to 7.9). Among children born in the United States, those who had traveled were 4.7 times more likely to have a positive skin test (95% CI, 2.0 to 11.2). Children who had a household visitor from a country having a high prevalence of tuberculosis were 2.4 times more likely to have a positive skin test than were those who did not have a visitor (95% CI, 1.0 to 5.5). These data indicate that travel to a country that has a high prevalence of tuberculosis or having a visitor from such countries increase the risk of tuberculous infection among young children. Physicians and tuberculosis control programs should incorporate questions about travel and visitors into their evaluations, and children with a history of extended travel should have a tuberculin skin test.
Antihistamine Drugs for Nausea and Vomiting Due to Streptomycin
Authors: J. R. Bignall, J. Crofton
Journal: BMJ (1949)

This toxic manifestation has been observed in 17 (35%) of 49 patients treated at the Brompton Hospital during the Medical Research Council trials of streptomycin in pulmonary tuberculosis, but in only four have symptoms been severe and persistent.Such toxic symptoms as urticaria are probably due to
Abortion restrictions increase at state level in US
Authors: M. McCarthy
Journal: BMJ (2013)

Last year 19 US states adopted new legislation restricting access to abortion services, finds an analysis by the Guttmacher Institute, an independent non-profit organization that focuses on sexual and reproductive health policy.1

All told, in 2012 states passed 43 provisions restricting access to abortion. The number was second only to the record breaking total of 92 passed in 2011.

Most of the provisions sought to limit the gestational age at which abortions are allowed, to block coverage of abortion services through the state health insurance exchanges established …
Old drugs for heart failure nearly halve deaths in black people
Authors: Scott Gottlieb
Journal: BMJ (2004)

Adding a dose of isosorbide dinitrate plus hydralazine to standard treatment for advanced heart failure can help black people live longer, shows a study. However, adding an angiotensin converting enzyme (ACE) inhibitor to the optimal treatment of stable heart disease offers no extra benefits.

Findings from two new studies were published this week to coincide with the annual meeting of the American Heart Association in New Orleans.

Researchers in the first study terminated their study …
Use of Macrophages to Target Therapeutic Adenovirus to Human Prostate Tumors
Authors: Munitta Muthana, Athina Giannoudis, Simon D. Scott, Hsin-Yu Fang, Seth B. Coffelt, Fiona J. Morrow, Craig Murdoch, Julian Burton, Neil Cross, Bernard Burke, Roshna Mistry, Freddie Hamdy, Nicola J. Brown, Lindsay Georgopoulos, Peter Hoskin, Magnus Essand, Claire E. Lewis, Norman J. Maitland
Journal: Cancer Research (2011)

New therapies are required to target hypoxic areas of tumors as these sites are highly resistant to conventional cancer therapies. Monocytes continuously extravasate from the bloodstream into tumors where they differentiate into macrophages and accumulate in hypoxic areas, thereby opening up the possibility of using these cells as vehicles to deliver gene therapy to these otherwise inaccessible sites. We describe a new cell-based method that selectively targets an oncolytic adenovirus to hypoxic areas of prostate tumors. In this approach, macrophages were cotransduced with a hypoxia-regulated E1A/B construct and an E1A-dependent oncolytic adenovirus, whose proliferation is restricted to prostate tumor cells using prostate-specific promoter elements from the TARP, PSA, and PMSA genes. When such cotransduced cells reach an area of extreme hypoxia, the E1A/B proteins are expressed, thereby activating replication of the adenovirus. The virus is subsequently released by the host macrophage and infects neighboring tumor cells. Following systemic injection into mice bearing subcutaneous or orthotopic prostate tumors, cotransduced macrophages migrated into hypoxic tumor areas, upregulated E1A protein, and released multiple copies of adenovirus. The virus then infected neighboring cells but only proliferated and was cytotoxic in prostate tumor cells, resulting in the marked inhibition of tumor growth and reduction of pulmonary metastases. This novel delivery system employs 3 levels of tumor specificity: the natural "homing" of macrophages to hypoxic tumor areas, hypoxia-induced proliferation of the therapeutic adenovirus in host macrophages, and targeted replication of oncolytic virus in prostate tumor cells.
Acute renal impairment in coronavirus-associated severe acute respiratory syndrome
Authors: Kwok Hong Chu, Wai Kay Tsang, Colin S. Tang, Man Fai Lam, Fernand M. Lai, Ka Fai To, Ka Shun Fung, Hon Lok Tang, Wing Wa Yan, Hilda W.H. Chan, Thomas S.T. Lai, Kwok Lung Tong, Kar Neng Lai
Journal: Kidney International (2005)
The measurement of nephron filtration rate and absolute reabsorption in the proximal tubule of the rabbit kidney.
Authors: A M Chonko, R W Osgood, A E Nickel, T F Ferris, J H Stein
Journal: Journal of Clinical Investigation (1975)

Micropuncture studies were performed in the rabbit to determine nephron filtration rate and absolute fluid reabsorption in the proximal tubule in order to compare the latter value with data obtained with the in vitro microperfusion technique. New Zealand white rabbits, 2-2.8 kg, were studied. Nephron filtration rate was 21 nl/min (n equal to 48) and absolute reabsorption along the length of the accesible portion of the proximal convoluted tubule was 10.3 nl/min. Correcting this value for tubular length gives a fluid reabsorption of approximately 1.9 nl/mm per min. In view of the marked difference between the in vivo and in vitro techniques and the various sources of error with each, this is reasonably similiar to the value of 1.3 nl/mm per min obtained in the isolated proximal convoluted tubule.
An In-Phantom Radiation Detector
Authors: Majic S. Potsaid, Goro Irie
Journal: New England Journal of Medicine (1961)

A SOLID, capable of detecting as well as measuring the amount of radiation and composed of several easily controlled organic molecules that can be prepared economically, has been devised for experimental and clinical applications.1 Owing to its characteristics it offers some completely new possibilities. By gross visual inspection it has permitted the study of radiation effects in a material whose density can be made closely equivalent to that of living tissues. The structural complex has been considered an in-phantom chemical radiation dosimeter where the dosimeter is the phantom and the phantom itself is a dosimeter.The system contains specific chemicals . . .
PHYSIOLOGY OF THE PYLORUS, PILLEUS VENTRICULI AND DUODENUM AS OBSERVED ROENTGENOGRAPHICALLY
Authors: LEWIS GREGORY COLE
Journal: JAMA (1913)

Until 1892 the commonly accepted theory of gastric evacuation had been that offered by Richet and Rossbach, that the stomach contents were first thoroughly mixed with the gastric juices and, after three or four hours, passed rapidly into the duodenum. This conception was discredited by the results of independent investigations on dogs by Hirsch (1892) and Mering (1893), who substituted for it the theory of a rhythmically opening and closing pylorus, through which evacuation began immediately after ingestion. In 1898 Canno announced the discovery of a progressive peristalsis in the cat, and eleven years later Kaestle, Rieder and Rosenthal demonstrated a corresponding phenomenon in the human being.  My conception of the gastric motor phenomenon has been previously described,1and will therefore be referred to only in brief. Like the heart-action, gastric action takes place in cycles, marked by a systole and diastole or an alternating contraction and relaxation of
Healing of Myocardial Infarcts in Dogs
Authors: Vincent Richard, Charles E. Murry, Keith A. Reimer
Journal: Circulation (1995)

Background Early reperfusion salvages ischemic myocardium and limits myocardial infarct size. However, the effects of late reperfusion, after the possibility for limitation of infarct size has passed, have not been completely elucidated. The purpose of this study was to ascertain the effect of reperfusion after 6 hours of ischemia on the rate of infarct healing and on the size and geometry of the resulting scars, as determined by gross and microscopic quantification. Methods and Results Myocardial infarcts were produced in anesthetized, open-chest dogs by occlusion of the circumflex coronary artery. They either were reperfused by removal of the occluding snare or were nonreperfused. The animals were allowed to recover for either 4 days, 2 weeks, or 6 weeks. At these times, infarct size, infarct dimensions (wall thickness and circumferential extent), and the proportion of infarct occupied by necrotic myocardium versus granulation tissue (evolving scar) were measured. At 4 days, infarcts were swollen in both nonreperfused and reperfused groups (increased thickness and circumferential extent of the area at risk). Conversely, at 6 weeks, the size, thickness, and circumferential extent of the scar all were decreased. Two common anatomic complications of human infarction, cardiac rupture and chronic infarct expansion (aneurysm), did not occur in this experimental model. Reperfusion at 6 hours did not affect initial infarct size (4 days) or scar size (6 weeks). At 2 weeks, reperfused infarcts were smaller and were composed of proportionately more granulation tissue and less nonresorbed necrosis than nonreperfused infarcts. Conclusions Thus, reperfusion accelerated the rate of infarct repair, ie, the replacement of necrotic myocardium by scar. Acceleration of infarct repair may be a beneficial effect of late reperfusion even after the opportunity for limitation of infarct size has passed.
Echocardiographic visualization of ventricular septal defect in infants and assessment of hemodynamic status using a contrast technique. Comparison of M-mode and two-dimensional imaging.
Authors: T Funabashi, H Yoshida, S Nakaya, T Maeda, N Taniguchi
Journal: Circulation (1981)

Twenty-seven patients with ventricular septal defect (VSD), ages 2 months to 2 years, were evaluated by both M-mode and two-dimensional echocardiography (2-D echo) with the aid of a peripheral venous contrast technique. M-mode echocardiography was unreliable for imaging VSD. Using 2-D echo, defects in the interventricular septum were visualized in all patients examined; defects in the membranous portion (24 patients) were visualized by the subcostal frontal approach and defects in the supracristal portion (three patients) by the subcostal sagittal approach. The 2-D echo contrast study revealed negative contrast jets appearing through the defect in the right ventricle in 22 patients with a pulmonary-to-systemic blood flow ratio greater than 2.0, and positive contrast jets appearing through the defect in the left ventricle in 13 patients with a right-to-left ventricular peak pressure ratio greater than 0.71. We conclude that 2-D echo with peripheral contrast technique confirmed the anatomic location of VSD and indicated the approximate right-to-left ventricular peak pressure ratio, showing the contrast material shunting through the defect itself.
Comprehensive Electrocardiography: Theory and Practice in Health and Disease
Authors: Edward K. Chung
Journal: JAMA (1989)

<i>Comprehensive Electrocardiography</i>consists of three volumes with 1785 pages, and it is truly a giant book in the field of electrocardiology. It is edited by two British cardiologists, with multiple contributors. Although I have reviewed numerous books in the field for various medical journals for 25 years, this is the only book that describes every aspect of electrocardiology not only in humans but also in various animals. As emphasized in the preface, the current knowledge of all aspects of theoretical and practical electrocardiology is included. One of the strong points is the vectorial approach in the understanding of a variety of electrocardiographic abnormalities. In addition, the references are also complete with up-to-date materials. It is amazing that some short articles (eg, "ECG of the Month") published in state journals are also included. The quality of the artwork, particularly the reproduction of the ECGs, is adequate in most chapters, but it
Quality of life measures in health care. I: Applications and issues in assessment.
Authors: R. Fitzpatrick, A. Fletcher, S. Gore, D. Jones, D. Spiegelhalter, D. Cox
Journal: BMJ (1992)

Many clinicians remain unsure of the relevance of measuring quality of life to their clinical practice. In health economics quality of life measures have become the standard means of assessing the results of health care interventions and, more controversially, the means of prioritising funding; but they have many other applications. This article--the first of three on measuring quality of life--reviews the instruments available and their application in screening programmes, audit, health care research, and clinical trials. Using the appropriate instrument is essential if outcome measures are to be valid and clinically meaningful.