tbuckley/cabot-search huggingface dataset:
Laminin-α4 and Integrin-Linked Kinase Mutations Cause Human Cardiomyopathy Via Simultaneous Defects in Cardiomyocytes and Endothelial Cells
Authors: Ralph Knöll, Ruben Postel, Jianming Wang, Ralph Krätzner, Gerrit Hennecke, Andrei M. Vacaru, Padmanabhan Vakeel, Cornelia Schubert, Kenton Murthy, Brinda K. Rana, Dieter Kube, Gudrun Knöll, Katrin Schäfer, Takeharu Hayashi, Torbjorn Holm, Akinori Kimura, Nicholas Schork, Mohammad Reza Toliat, Peter Nürnberg, Heinz-Peter Schultheiss, Wolfgang Schaper, Jutta Schaper, Erik Bos, Jeroen Den Hertog, Fredericus J.M. van Eeden, Peter J. Peters, Gerd Hasenfuss, Kenneth R. Chien, Jeroen Bakkers
Journal: Circulation (2007)

Extracellular matrix proteins, such as laminins, and endothelial cells are known to influence cardiomyocyte performance; however, the underlying molecular mechanisms remain poorly understood.We used a forward genetic screen in zebrafish to identify novel genes required for myocardial function and were able to identify the lost-contact (loc) mutant, which encodes a nonsense mutation in the integrin-linked kinase (ilk) gene. This loc/ilk mutant is associated with a severe defect in cardiomyocytes and endothelial cells that leads to severe myocardial dysfunction. Additional experiments revealed the epistatic regulation between laminin-alpha4 (Lama4), integrin, and Ilk, which led us to screen for mutations in the human ILK and LAMA4 genes in patients with severe dilated cardiomyopathy. We identified 2 novel amino acid residue-altering mutations (2828C>T [Pro943Leu] and 3217C>T [Arg1073X]) in the integrin-interacting domain of the LAMA4 gene and 1 mutation (785C>T [Ala262Val]) in the ILK gene. Biacore quantitative protein/protein interaction data, which have been used to determine the equilibrium dissociation constants, point to the loss of integrin-binding capacity in case of the Pro943Leu (Kd=5+/-3 micromol/L) and Arg1073X LAMA4 (Kd=1+/-0.2 micromol/L) mutants compared with the wild-type LAMA4 protein (Kd=440+/-20 nmol/L). Additional functional data point to the loss of endothelial cells in affected patients as a direct consequence of the mutant genes, which ultimately leads to heart failure.This is the first report on mutations in the laminin, integrin, and ILK system in human cardiomyopathy, which has consequences for endothelial cells as well as for cardiomyocytes, thus providing a new genetic basis for dilated cardiomyopathy in humans.
Lilly to provide consumer leaflet on Darvon
Authors: John Elliott
Journal: JAMA (1979)

In the continuing saga of the widely used pain-killing drug propoxyphene hydrochloride, Eli Lilly and Company, the principal manufacturer of the drug, has agreed to voluntarily distribute a warning on the hazards of using its product (Darvon) in excess or in combination with other drugs. The Food and Drug Administration has announced that the new consumer leaflet will be available from pharmacists when prescriptions for Darvon are filled. "Darvon is a safe drug when used properly," said acting FDA Commissioner Sherwin Gardner. He added, however, that there is a "potentially lethal" risk involved when the drug is used with alcohol, tranquilizers, or sedatives. On his last day in office, however, former HEW Secretary Joseph Califano criticized the warnings as inadequate. He said that they fail to mention such things as the maximum recommended dose or the signs of drug dependency. Lilly manufactures at least 80% of the propoxyphene used in
Failure of mannitol to reduce myocardial infarct size in the baboon
Authors: R. N Harada, W. Limm, L. H Piette, J J. McNamara
Journal: Cardiovascular Research (1992)

Journal Article Failure of mannitol to reduce myocardial infarct size in the baboon Get access Russell N Harada, Russell N Harada Correspondence to Professor McNamara (Department of Surgery, Queen's Medical Center). Search for other works by this author on: Oxford Academic PubMed Google Scholar Whitney Limm, Whitney Limm Search for other works by this author on: Oxford Academic PubMed Google Scholar Lawrence H Piette, Lawrence H Piette Search for other works by this author on: Oxford Academic PubMed Google Scholar J Judson McNamara J Judson McNamara Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 26, Issue 9, September 1992, Pages 893–896, https://doi.org/10.1093/cvr/26.9.893 Published: 01 September 1992 Article history Received: 17 December 1991 Accepted: 16 March 1992 Published: 01 September 1992
Magnetic Fields and Cancer: Animal and Cellular Evidence: An Overview
Authors: Bo Holmberg
Journal: Environmental Health Perspectives (1995)

A few animal studies on the possible carcinogenic effect of magnetic fields have been published. They have been designed to reveal a possible tumor promotion obtained by applying continuous or pulsed alternating fields at flux densities varying between 0.5 microT and 30 mT on mice or rats initiated with different initiators. One study with 2 mT applied on DMBA-initiated mice may suggest a copromotive effect together with the promoter TPA. Another study on rats suggests an inhibitory effect by a magnetic field on rat liver foci formation, induced with DENA. Cell studies show that magnetic fields at some frequencies, amplitudes, and wave forms interact with biological systems. Thus effects have been seen, e.g., on enzymes related to growth regulation, on calcium balance in the cell, on gene expression, and on pineal metabolism and its excretion of the oncostatic melatonin. Cellular and physiologic studies thus suggest effects that may be related to cell multiplication and tumor promotion.
SALMONELLA SCHOTTMÜLLERI ISOLATED FROM SACROLUMBAR LESION OF TWENTY-FOUR YEARS' DURATION
Authors: E. E. Ecker
Journal: JAMA (1942)

Since Achard and Bensaude<sup>1</sup>established the etiology of paratyphoid fever in 1896, the causative organism and its related species and types have been isolated in numerous instances from abscesses of widely different tissues. The literature, however, offers only 3 doubtful cases in which an organism of the Salmonella schottmülleri type has been obtained from infections involving the bones. Achard and Bensaude were the first also to describe a case of purulent arthritis from which this organism was recovered. In 1900 Cushing<sup>2</sup>reported the discovery of a paratyphoid bacillus from a costochondral abscess, and in 1916 Gildemeister<sup>3</sup>isolated a similar organism from a periosteal lesion of the forearm. There is little assurance that the organisms found in these early cases are of the true Schottmüller type. The complex antigenic constitution of this group of organisms was not known and serologic methods of differentiation therefore still were undeveloped. <h3>REPORT</h3>
The level of AKT phosphorylation on threonine 308 but not on serine 473 is associated with high-risk cytogenetics and predicts poor overall survival in acute myeloid leukaemia
Authors: N Gallay, C Dos Santos, L Cuzin, M Bousquet, V Simmonet Gouy, C Chaussade, M Attal, B Payrastre, C Demur, C Récher
Journal: Leukemia (2009)
Survey of public information about ongoing clinical trials funded by industry: evaluation of completeness and accessibility
Authors: E. Manheimer
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objective:</b> To evaluate the completeness and accessibility of public information about US clinical trials of drugs in development. <b>Design:</b> Review of online registers of clinical trials. <b>Data sources:</b> Drugs in phase III trials were identified using three drug industry sources: PhRMA Survey, What9s in the Pipeline, and the NDA Pipeline. Drug trials were then searched for on the following publicly accessible registers of clinical trials: CancerNet.gov, CenterWatch.com, ClinicalTrials.gov, and registers associated with the 37 "Comprehensive Cancer Centers" designated by the National Cancer Institute. <b>Main outcome measure:</b> Extent of availability of public information on phase III trials of drugs in development for treating either prostate or colon cancer. <b>Results:</b> Search of industry sources identified 12 drugs for prostate cancer and 20 for colon cancer undergoing phase III trials. The most comprehensive publicly available register, ClinicalTrials.gov, contained trial listings for only seven of the prostate cancer drugs and 10 of the colon cancer drugs. Trials of three prostate cancer and three colon cancer drugs were listed on only one register each. A substantial proportion of trials of prostate cancer drugs (3/12) and colon cancer drugs (8/20) were not associated with trial listings in any registers. <b>Conclusions:</b> Existing trials registers are unlikely to be meeting user needs since many ongoing drug trials are not listed. There is a clear need for a comprehensive clinical trials register encompassing all ongoing trials, including industry sponsored trials.
Thromboxane-mediated alveolar responses to acute obstruction of the pulmonary vasculature.
Authors: A Mitra, S J Feinmark, P O Alderson
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

To investigate the mechanisms responsible for the accelerated radioaerosol transalveolar clearance rates caused by acute balloon occlusion of the pulmonary arterial tree in dogs, the effects of vagal tone (n = 5) and prostaglandins (n = 21) including thromboxane were evaluated. In 15 animals, serial pulmonary arterial and aortic blood samples were acquired to evaluate pertinent metabolic products. Balloon occlusion of a localized arterial territory caused significant acceleration of technetium-99m diethylenetriamine pentaacetic acid (Tc-99m DTPA) clearance in the zone immediately distal to the occlusion (baseline clearance half-time 23.1 +/- 0/7 min versus 19.3 +/- 0.4 min, mean +/- SEM, p < 0.05). Vagotomy had no effect on occlusion-accelerated clearance. However, significant (p < 0.05) normalization did occur in the presence of indomethacin (21.9 +/- 0.4 min) and meclofenamic acid (20.4 +/- 0.5 min). Plasma values of thromboxane rose dramatically (pulmonary blood baseline 119 pg/ml to > 40,000 pg/ml) and transiently immediately after pulmonary vascular occlusion, and this rise was blunted significantly (peak pulmonary thromboxane B2 [TXB2] concentration = 668 pg/ml, p < 0.05) by meclofenamic acid. Significant normalization of local DTPA clearance rates also occurred in the presence of a thromboxane receptor blocker (n = 4), even when blood levels of thromboxane were elevated. Changes in transalveolar DTPA clearance rates after balloon occlusion of pulmonary arteries seem to a significant extent to be thromboxane-mediated.
EU countries disagree over stockpiling drugs for flu pandemic
Authors: Rory Watson
Journal: BMJ (2006)

Members of the European Union cannot agree on whether or not to create a European stockpile of antiviral drugs for use in the event of an influenza pandemic, if the avian flu virus should mutate and become transmissible between humans.

Robert Madelin, director general of the European Commission's department responsible for health and consumer affairs, believes that such a stockpile should be created.

“If we had one we would be able to give additional antiviral stocks when the first outbreak occurs. It could …
Netherlands drops plans to deliver acute obstetric care in 15 minutes
Authors: T. Sheldon
Journal: BMJ (2012)

<b>Background:</b> Expiratory flow limitation (EFL) is an hallmark of COPD. However has not implemented in the baseline routine functional assessment yet. <b>Aim:</b> to evaluate if the measurement of EFL by FOT could contribute to highlight pathophysiological mechanisms of improvement after PR. <b>Method:</b> in 75 stable moderate to very severe COPD patients, before and after PR, EFL as the within-breath change in reactance (DXrs), pulmonary function tests and rehabilitation outcomes were evaluated. <b>Results:</b> In the patients as a whole, after PR, DXrs decreased significantly (p&lt;0.05). Based on the cut-off of DXrs&gt;2.81 [cmH2O/(L/s)], patients were divided into two groups: flow-limited (FL, 36 patients, DXrs 5.14±2.6) and not flow-limited (NFL, 39 patients, DXrs 1.04±0.9) patients. Before PR FL patients were more severely obstructed (FEV1% 34.6±9.6 vs 52.0±20.6, p&lt;0.001), hyperinflated (FRC%pred: 157.7±39.1 vs 135.9±40.9 p&lt;0.05) and showed a lower IC% (73.0±15.9 vs 87.5±18.4 p&lt;0.001). Moreover, in the two groups we selected patients with severe obstruction (FEV1&lt;40%pv); before PR, DXrs was the only difference between the two severe groups (p&lt; 0.001). After PR, FL and NFL patients improved significantly dyspnea, 6MWT and health status; however, severe FL decreased DXrs significantly (p&lt;0.001) and showed a greater 6MWT change (p&lt;0.03) than NFL severe patients. <b>Conclusions:</b> FOT measures provide new supplementary information to pulmonary functional evaluation in COPD patients enrolled in PR. These preliminary data show that the change in EFL could contribute to the effect of PR in severe patients.
The levels of clarithromycin and its 14-hydroxy metabolite in the lung
Authors: D Honeybourne, F Kees, JM Andrews, D Baldwin, R Wise
Journal: European Respiratory Journal (1994)

Clarithromycin is a new macrolide that has a longer half-life than erythromycin and is claimed to reach higher tissue concentrations. We aimed to investigate whether, following oral administration, the drug and its 14-hydroxy metabolite reach levels in lung tissue that are likely to be clinically effective against common respiratory pathogens. Ten patients undergoing diagnostic bronchoscopy received seven doses of clarithromycin, 500 mg b.i.d. orally. Bronchoscopy was performed at a mean time of 4.25 h after the last dose. At bronchoscopy, bronchial biopsies and bronchoalveolar lavage were performed. Clarithromycin and its 14-OH metabolite were measured in serum, bronchial biopsies, epithelial lining fluid (ELF) and alveolar cells. Mean levels of clarithromycin were 4.0 mg.l-1 in serum, 16.8 mg.kg in bronchial biopsies, 20.5 mg.l-1 in ELF and 372.7 mg.l-1 in alveolar cells. The equivalent levels of 14-OH metabolite were 0.7, 2.7, 1.9 and 38.6 mg.l-1, respectively. We conclude that there is considerable concentration of clarithromycin and its 14-OH metabolite in alveolar cells, and to a lesser extent in bronchial tissue and ELF; this implies efficacy against susceptible organisms at these sites.
MAJOR AMPUTATIONS AND HOT WATER DRESSINGS.
Authors: H. H. CLARK
Journal: JAMA (1883)

[Read to the Tri-State Medical Society.] Mr. President and Gentlemen:—Amputation of the thigh or of the arm at the shoulder rank as the most fatal of surgical procedures. The causes of this fatality we shall not stop to consider in full, but simply ply enumerate such as are specially presented in the cases we bring to your notice to-day, and to which our treatment was specially directed, namely, shock, hæmorrhage and gangrene. I enumerate them in the order of their frequency as occurring in these cases. Shock, more or less severe, is always present. Hæmorrhage, in some form, is not infrequent, and gangrene occasionally presents in civil practice. To prevent these, or they having occurred to abridge their severity, is ever a foremost consideration of the surgeon. The latter fact has induced me to pursue in all cases of surgery, of whatever magnitude, the treatment to which I would to-day
Cognitive impairment and mortality in a cohort of elderly people
Authors: C. R Gale, C. N Martyn, C. Cooper
Journal: BMJ (1996)

To investigate the relation between cognitive function and cause specific mortality in people aged 65 and over. DESIGN-A 20 year follow up study of a cohort of randomly selected elderly people living in the community who in 1973-4 had taken part in a nutritional survey funded by the Department of Health and Social Security.Eight areas in Britain (five in England, two in Scotland, and one in Wales).921 men and women whose cognitive function was assessed by a geriatrician in 1973-4 and for whom data on health, socioeconomic circumstances, and diet had been recorded.Cognitive impairment was associated with increased mortality, in particular death from ischaemic stroke. Those who scored 7 or less on the Hodkinson mental test had a relative risk of dying from stroke of 2.8 (95% confidence interval 1.4 to 5.5), compared with those who gained the maximum score (10), after adjustment for age, sex, blood pressure, serum cholesterol concentration, and vitamin C intake. These associations were independent of illness or social class. At the time of the nutritional survey, cognitive function was poorest in those with the lowest vitamin C status, whether measured by dietary intake or plasma ascorbic acid concentration. The relation between vitamin C status and cognitive function was independent of age, illness, social class, or other dietary variables.The relation between cognitive function and risk of death from stroke suggests that cerebrovascular disease is an important cause of declining cognitive function. Vitamin C status may be a determinant of cognitive function in elderly people through its effect on atherogenesis. A high vitamin C intake may protect against both cognitive impairment and cerebrovascular disease.
Scanning with 18F-FDG-PET/CT for Detection of Pelvic Nodal Involvement in Inguinal Node-Positive Penile Carcinoma
Authors: Niels M. Graafland, Joost A.P. Leijte, Renato A. Valdés Olmos, Cornelis A. Hoefnagel, Hendrik J. Teertstra, Simon Horenblas
Journal: European Urology (2009)
Pulmonary Light and Heavy Chain Deposition Disease
Authors: William Makis, Vilma Derbekyan, Javier-A Novales-Diaz
Journal: Clinical Nuclear Medicine (2010)

A 64-year-old man with a history of smoking and asbestos exposure was referred for an F-18 FDG PET/CT, to evaluate multiple growing lung nodules that had been found incidentally on prior chest CTs. The PET/CT showed multiple hypermetabolic nodules in both the lungs, with varying intensity of FDG uptake, raising the suspicion of multifocal malignancy. Wedge resections of the right lung were done to remove the 2 most hypermetabolic nodules, and histologic evaluation revealed pulmonary light and heavy chain deposition disease. A follow-up PET/CT performed 1 year later showed another slowly growing nodule in the left lung with a significant increase in F-18 FDG uptake. Only 22 cases of pulmonary light chain deposition disease have been reported in the literature. This is a report of F-18 FDG uptake in nodules of pulmonary light chain deposition disease. These nodules can grow in size and can show increased F-18 FDG uptake on follow-up studies, mimicking a growing lung malignancy.
Diuretic Therapy, Hypertension, and Cardiac Arrest
Authors: J. Thomas Bigger
Journal: New England Journal of Medicine (1994)

In this issue of the Journal, Siscovick et al. report a case-control study that evaluated the risk of cardiac arrest associated with diuretic treatment of hypertension1. The authors are aware of the pitfalls of a case-control study and have taken precautions to avoid them. An increasing dose of a thiazide diuretic was associated with an increasing rate of cardiac arrest. The combination of a thiazide diuretic and a potassium-sparing diuretic was associated with a lower rate of cardiac arrest than was found with a thiazide diuretic either alone or combined with potassium supplements. The rate of cardiac arrest was . . .
Zinc supplementation reverses alcohol-induced steatosis in mice through reactivating hepatocyte nuclear factor-4α and peroxisome proliferator-activated receptor-α
Authors: Xinqin Kang, Wei Zhong, Jie Liu, Zhenyuan Song, Craig J. McClain, James Y. Kang, Zhanxiang Zhou
Journal: Hepatology (2009)

Alcoholic steatosis is a fundamental metabolic disorder in the progression of alcoholic liver disease. Zinc deficiency is one of the most consistently observed biochemical/nutritional manifestations of alcoholic liver disease. The purpose of this study is to determine whether dietary zinc supplementation to mice previously exposed to alcohol could reverse alcoholic steatosis. Male 129S mice were pair-fed an alcohol or isocaloric maltose dextrin liquid diet for 16 weeks with or without dietary zinc supplementation for the last 4 weeks. Zinc supplementation significantly attenuated alcohol-mediated increases in hepatic triglyceride, cholesterol, and free fatty acids in association with accelerated hepatic fatty acid oxidation and very low density lipoproteins (VLDL) secretion. Hepatic genes related to fatty acid oxidation and VLDL secretion were up-regulated by zinc supplementation, which was accompanied by restoring activity of hepatocyte nuclear factor-4α (HNF-4α) and peroxisome proliferators activated receptor-α (PPAR-α). Zinc supplementation enhanced alcohol metabolism and attenuated oxidative stress and liver injury. Zinc supplementation also normalized alcohol-mediated increases in plasma triglycerides and partially reversed decrease in gonadal adipose depot mass. Studies in HepG2 cells showed that zinc deprivation significantly suppressed the DNA-binding activities of HNF-4α and PPAR-α, and reduced HNF-4α and PPAR-α target proteins. Consequently, zinc deprivation caused cellular accumulation of lipid droplets, triglycerides and free fatty acids in the HepG2 cells. Conclusion: Zinc supplementation reverses alcoholic steatosis, and reactivation of HNF-4α and PPAR-α by increasing zinc availability and inhibiting oxidative stress are potential mechanisms underlying these beneficial effects of zinc on hepatic lipid homeostasis. (Hepatology 2009.)
Protozoan Parasites of Domestic Animals and of Man
Authors: Jeanette C. Opsahl
Journal: JAMA (1962)

Protozoa are among the most important causes of disease in both man and domestic animals. Malaria, while often believed to be no longer important in the United States, still holds first place among the world's human diseases. Amebic dysentery, trypanosomiasis, and leishmaniasis are among other important protozan diseases of man. Domestic animals suffer heavy losses from coccidiosis, trypanosomiasis, trichomoniasis, and many others. At one time it was thought that man and the lower animals each had their own protozoan parasites and their own diseases and that each of these moved in its own separate sphere. We know now that this is not true. As our knowledge has grown, we have come to recognize a growing number of parasites and diseases which are shared by man and lower animals. As a consequence, the zoonoses—diseases common to man and animals—are receiving more and more attention, and domestic and wild animals are being