tbuckley/cabot-search huggingface dataset:
Hepatitis C virus NS4B protein targets STING and abrogates RIG-I-mediated type I interferon-dependent innate immunity
Authors: Sayuri Nitta, Naoya Sakamoto, Mina Nakagawa, Sei Kakinuma, Kako Mishima, Akiko Kusano-Kitazume, Kei Kiyohashi, Miyako Murakawa, Yuki Nishimura-Sakurai, Seishin Azuma, Megumi Tasaka-Fujita, Yasuhiro Asahina, Mitsutoshi Yoneyama, Takashi Fujita, Mamoru Watanabe
Journal: Hepatology (2012)

Hepatitis C virus (HCV) infection blocks cellular interferon (IFN)-mediated antiviral signaling through cleavage of Cardif by HCV-NS3/4A serine protease. Like NS3/4A, NS4B protein strongly blocks IFN-β production signaling mediated by retinoic acid-inducible gene I (RIG-I); however, the underlying molecular mechanisms are not well understood. Recently, the stimulator of interferon genes (STING) was identified as an activator of RIG-I signaling. STING possesses a structural homology domain with flaviviral NS4B, which suggests a direct protein-protein interaction. In the present study, we investigated the molecular mechanisms by which NS4B targets RIG-I-induced and STING-mediated IFN-β production signaling. IFN-β promoter reporter assay showed that IFN-β promoter activation induced by RIG-I or Cardif was significantly suppressed by both NS4B and NS3/4A, whereas STING-induced IFN-β activation was suppressed by NS4B but not by NS3/4A, suggesting that NS4B had a distinct point of interaction. Immunostaining showed that STING colocalized with NS4B in the endoplasmic reticulum. Immunoprecipitation and bimolecular fluorescence complementation (BiFC) assays demonstrated that NS4B specifically bound STING. Intriguingly, NS4B expression blocked the protein interaction between STING and Cardif, which is required for robust IFN-β activation. NS4B truncation assays showed that its N terminus, containing the STING homology domain, was necessary for the suppression of IFN-β promoter activation. NS4B suppressed residual IFN-β activation by an NS3/4A-cleaved Cardif (Cardif1-508), suggesting that NS3/4A and NS4B may cooperate in the blockade of IFN-β production.NS4B suppresses RIG-I-mediated IFN-β production signaling through a direct protein interaction with STING. Disruption of that interaction may restore cellular antiviral responses and may constitute a novel therapeutic strategy for the eradication of HCV.
The Value of Geriatric Interventions
Authors: Edward W. Campion
Journal: New England Journal of Medicine (1995)

For vulnerable elderly patients, hospitalization can be hazardous.13 Too often their treatment is complicated by delirium, depression, adverse drug reactions, poor nutrition, and loss of precious physical strength. Too often their pneumonia is cured or their hip fractures repaired, but they never regain the independence they once had. Over the past 15 years, programs in geriatrics have developed at most American medical centers and a prime clinical mission has been to achieve better results for hospitalized, high-risk elderly patients. There are two main strategies. One is to admit older patients at risk to a specialized unit for acute or . . .
Regression of “Gray Zone” Exercise-Induced Concentric Left Ventricular Hypertrophy During Prescribed Detraining
Authors: Rory B. Weiner, Francis Wang, Brant Berkstresser, Jonathan Kim, Thomas J. Wang, Gregory D. Lewis, Adolph M. Hutter, Michael H. Picard, Aaron L. Baggish
Journal: Journal of the American College of Cardiology (2012)
Potential impact of carbohydrate and fat intake on pathological left ventricular hypertrophy
Authors: N SHARMA, I OKERE, M DUDA, D CHESS, K OSHEA, W STANLEY
Journal: Cardiovascular Research (2006)

Currently, a high carbohydrate/low fat diet is recommended for patients with hypertension; however, the potentially important role that the composition of dietary fat and carbohydrate plays in hypertension and the development of pathological left ventricular hypertrophy (LVH) has not been well characterized. Recent studies demonstrate that LVH can also be triggered by activation of insulin signaling pathways, altered adipokine levels, or the activity of peroxisome proliferator-activated receptors (PPARs), suggesting that metabolic alterations play a role in the pathophysiology of LVH. Hypertensive patients with high plasma insulin or metabolic syndrome have a greater occurrence of LVH, which could be due to insulin activation of the serine-threonine kinase Akt and its downstream targets in the heart, resulting in cellular hypertrophy. PPARs also activate cardiac gene expression and growth and are stimulated by fatty acids and consumption of a high fat diet. Dietary intake of fats and carbohydrate and the resultant effects of plasma insulin, adipokine, and lipid concentrations may affect cardiomyocyte size and function, particularly in the setting of chronic hypertension. This review discusses potential mechanisms by which dietary carbohydrates and fats ca affect cardiac growth, metabolism, and function, mainly in the context of pressure overload-induced LVH.
India to ban female sterilisation with malaria drug
Authors: G. Mudur
Journal: BMJ (1998)

The Indian drug control agency has decided to ban the use of the antimalarial drug quinacrine for female sterilisation. The decision, announced last week, follows a petition by activists alleging that more than 30000 women in India have been sterilised with quinacrine over the past five years without the approval of health authorities.

Quinacrine has been used as an antimalarial drug for nearly five decades. Quinacrine pellets inserted into the uterus can lead to fibrosis and block …
Left Ventricular Geometry and Severe Left Ventricular Hypertrophy in Children and Adolescents With Essential Hypertension
Authors: Stephen R. Daniels, Jennifer M. H. Loggie, Philip Khoury, Thomas R. Kimball
Journal: Circulation (1998)

Left ventricular (LV) hypertrophy has been established as an independent risk factor for cardiovascular disease in adults. Recent research has refined this relationship by determining a cutpoint of 51 g/m(2.7) for LV mass index indicative of increased risk and defining LV geometric patterns that are associated with increased risk. The purpose of this study was to evaluate severe LV hypertrophy and LV geometry in children and adolescents with essential hypertension.A cross-sectional study of young patients (n=130) with persistent blood pressure elevation above the 90th percentile was conducted. Nineteen patients (14%) had LV mass greater than the 99th percentile; 11 of these were also above the adult cutpoint of 51 g/m(2.7). Males, subjects with greater body mass index, and those who had lower heart rate at maximum exercise were at significantly (P<.05) higher risk of severe LV hypertrophy. In addition, 22 patients (17%) had concentric LV hypertrophy, a geometric pattern that is associated with increased risk of cardiovascular disease in adults. Seven patients had LV mass index above the cutpoint and concentric hypertrophy. No consistent significant determinants of LV geometry were identified in these children and adolescents with hypertension.Severe LV hypertrophy and abnormal LV geometry are relatively prevalent in young patients with essential hypertension. These findings suggest that these patients may be at risk for future cardiovascular disease and underscore the importance of recognition and treatment of blood pressure elevation in children and adolescents. Weight loss is an important component of therapy in young patients with essential hypertension who are overweight.
George John Romanes
Authors: N. Stafford
Journal: BMJ (2014)

Anatomy lecturer whose early research improved understanding of the spinal motor system



Throughout a long and distinguished career in medicine, George John Romanes was widely recognised as an exceptional teacher of anatomy and a highly competent administrator. In the 1940s and early 1950s, however, his focus was research, and his papers investigating the spinal motor system helped open the door to a better understanding of neuron circuitry.

“His published papers have stood the test of time,” said John S Kelly, emeritus professor of pharmacology at the University of Edinburgh and coauthor of a 2011 article in the journal Neuron that detailed the importance of Romanes’s research.1

Romanes wrote his first paper, “The spinal accessory nerve in the sheep,”2 in 1940 while still a doctoral student in anatomy at the University of Cambridge. The next year he published his second paper, “Cell columns in the spinal cord of a human foetus of fourteen weeks.”3 By 1949, when he was awarded a Commonwealth Fund fellowship, he had written a dozen papers on the spinal nervous system.

The fellowship allowed him to spend a year deepening …
DETERMINATION OF THE URINARY NEUTROPHIL GELATINASE–ASSOCIATED LIPOCALIN AS AN EARLY MARKER OF CONTRAST INDUCED ACUTE KIDNEY INJURY AFTER CORONARY CATHETERIZATION
Authors: Matteo Tebaldi, Marco Valgimigli, Gianluca Campo, Stefania Gambetti, Laura Bristot, Monia Monti, Roberto Ferrari
Journal: Journal of the American College of Cardiology (2013)
O157 VIRUS INFECTION OF HEPATIC SINUSOIDAL ENDOTHELIAL CELLS REGULATES HEPATIC T CELL RECRUITMENT AND ACTIVATION
Authors: T. Bruns, H.W. Zimmermann, A. Pachnio, K.-K. Li, P.J. Trivedi, G. Reynolds, S. Hubscher, Z. Stamatalo, P.W. Badenhorst, C.J. Weston, P.A. Moss, D.H. Adams
Journal: Journal of Hepatology (2014)
Overestimation of pediatric cardiac output by thermal indicator loss.
Authors: G F Maruschak, A M Potter, J F Schauble, M C Rogers
Journal: Circulation (1982)

The accurate measurement of pediatric cardiac output by thermodilution requires that the quantity of cold indicator introduced into the central circulation be known. This study defines an important source of error in the correction factor for the amount of heat gained by small volumes of cold injectate during passage through pediatric catheter systems. This error may result in significant overestimation of cardiac output (as much as 59%) when blood at body temperature is withdrawn into the injection lumen of the pediatric catheter before the injection.
Pulmonary Ventilation/Perfusion and Reverse Mismatches in an Infant
Authors: JAMES D. SLAVIN, JOHN MATHEWS, RICHARD P. SPENCER
Journal: Clinical Nuclear Medicine (1985)

A male infant, with bronchopulmonary dysplasia and ventilator dependence, had lung ventilation (Xe-133 gas) and perfusion (Tc-99m MAA) imaging performed. The examination revealed a region that was ventilated but not perfused (mismatch) and a separate area that was perfused but not ventilated (reverse mismatch). The basis of both abnormalities is suspected to be related to bronchopulmonary dysplasia, atelectasis and/or mechanical ventilation. Ventilation/perfusion mismatches and reverse mismatches can occur in the same patient.
The MGH Trustees Say No to Heart Transplants
Authors: Alexander Leaf
Journal: New England Journal of Medicine (1980)

On February 1 of this year the trusters of the Massachusetts General Hospital, after months of deliberation, announced that they had decided against allowing the hospital's cardiac surgical service to begin a limited program of heart transplantation. This decision, which made headlines all over the country, is likely to be quoted and debated for a long time to come. It raises important issues about the allocation of scarce and costly health-care resources in this country. In Great Britain the National Health Service has recently lifted an embargo on payments for heart transplantations that it had imposed in 1973, but the . . .
P595 THE EXPRESSION AND FUNCTION OF THE TNF SUPERFAMILY LIGAND, TWEAK AND ITS RECEPTOR FN14 IN LIVER FIBROSIS
Authors: A. Wilhelm, M. Munir, E.H. Humphreys, D.H. Adams, L.C. Burkly, S.C. Afford, C.J. Weston
Journal: Journal of Hepatology (2014)
Misleading relative risks?
Authors: A. J Petrie
Journal: BMJ (2009)

<h3>Objectives</h3> To quantify the extent to which guideline recommendations for routine testing for HIV are adhered to outside of genitourinary medicine (GUM), sexual health (SH) and antenatal clinics. <h3>Methods</h3> A systematic review of published data on testing levels following publication of 2008 guidelines was undertaken. Medline, Embase and conference abstracts were searched according to a predefined protocol. We included studies reporting the number of HIV tests administered in those eligible for guideline recommended testing. We excluded reports of testing in settings with established testing surveillance (GUM/SH and antenatal clinics). A random effects meta-analysis was carried out to summarise level of HIV testing across the studies identified. <h3>Results</h3> Thirty studies were identified, most of which were retrospective studies or audits of testing practice. Results were heterogeneous. The overall pooled estimate of HIV test coverage was 27.2% (95% CI 22.4% to 32%). Test coverage was marginally higher in patients tested in settings where routine testing is recommended (29.5%) than in those with clinical indicator diseases (22.4%). Provider test offer was found to be lower (40.4%) than patient acceptance of testing (71.5%). <h3>Conclusions</h3> Adherence to 2008 national guidelines for HIV testing in the UK is poor outside of GUM/SH and antenatal clinics. Low levels of provider test offer appear to be a major contributor to this. Failure to adhere to testing guidelines is likely to be contributing to late diagnosis with implications for poorer clinical outcomes and continued onwards transmission of HIV. Improved surveillance of HIV testing outside of specialist settings may be useful in increasing adherence testing guidelines.
Points from Letters: Inversion of the Appendix
Authors: R. S. Arnott
Journal: BMJ (1974)

some extent those retiring between 1969 and 1972 will be given less than their olleagues who retired after 24 March 1972.This means that there has to be for them a different formula from that for general practitioners retiring after 24 March 1972 and it is on this that there have been some-what protracted negotiations with the De- partment.We have certainly put every pressure on the Department to expedite matters and we hope that with the help of our professional expert advisers we -may be able to reach an early settlement."-ED.,
The type 2 iodothyronine deiodinase is essential for adaptive thermogenesis in brown adipose tissue
Authors: Lucia A. de Jesus, Suzy D. Carvalho, Mirian O. Ribeiro, Mark Schneider, Sung-Woo Kim, John W. Harney, P. Reed Larsen, Antonio C. Bianco
Journal: Journal of Clinical Investigation (2001)

Type 2 iodothyronine deiodinase (D2) is a selenoenzyme, the product of the recently cloned cAMP-dependent Dio2 gene, which increases 10- to 50-fold during cold stress only in brown adipose tissue (BAT). Here we report that despite a normal plasma 3,5,3'-triiodothyronine (T3) concentration, cold-exposed mice with targeted disruption of the Dio2 gene (Dio2(-/-)) become hypothermic due to impaired BAT thermogenesis and survive by compensatory shivering with consequent acute weight loss. This occurs despite normal basal mitochondrial uncoupling protein 1 (UCP1) concentration. In Dio2(-/-) brown adipocytes, the acute norepinephrine-, CL316,243-, or forskolin-induced increases in lipolysis, UCP1 mRNA, and O(2) consumption are all reduced due to impaired cAMP generation. These hypothyroid-like abnormalities are completely reversed by a single injection of T3 14 hours earlier. Recent studies suggest that UCP1 is primarily dependent on thyroid hormone receptor beta (TR beta) while the normal sympathetic response of brown adipocytes requires TR alpha. Intracellularly generated T3 may be required to saturate the TR alpha, which has an approximately fourfold lower T3-binding affinity than does TR beta. Thus, D2 is an essential component in the thyroid-sympathetic synergism required for thermal homeostasis in small mammals.
Is glucose/amino acid supplementation after exercise an aid to strength training?
Authors: A G Williams, M van den Oord, A Sharma, D A Jones
Journal: British Journal of Sports Medicine (2001)

The precise timing of carbohydrate and amino acid ingestion relative to a bout of resistance exercise may modulate the training effect of the resistance exercise.To assess whether regular glucose/amino acid supplementation immediately after resistance exercise could enhance the gain in muscle strength brought about by resistance training.Seven untrained participants with a median age of 23 years and mean (SD) body mass 68.9 (13.5) kg resistance trained on a leg extension machine for five days a week for 10 weeks, using four sets of 10 repetitions. Alternate legs were trained on successive days, one leg each day. Subjects ingested either a supplement including 0.8 g glucose/kg and 0.2 g amino acids/kg, or placebo, on alternate training days immediately after training. Therefore the supplement was always ingested after training the same leg (supplement leg). Isometric, isokinetic, and 1 repetition maximum (RM) strength were measured before, during, and after training. Blood samples were analysed to determine the acute responses of insulin and glucose to resistance exercise and supplementation or placebo.Serum insulin concentration peaked 20 minutes after supplement ingestion at ninefold the placebo level, and remained significantly elevated for at least 80 minutes (p<0.01). Isometric, isokinetic, and 1 RM strength improved on both supplement and placebo legs (p<0.05). There were no significant differences in the gain in strength between the supplement leg and the placebo leg (p>0.05).Regular glucose/amino acid supplementation immediately after resistance exercise is unlikely to enhance the gain in muscle strength brought about by resistance training.
Postexertional airway rewarming and thermally induced asthma. New insights into pathophysiology and possible pathogenesis.
Authors: E R McFadden, K A Lenner, K P Strohl
Journal: Journal of Clinical Investigation (1986)

To determine if postexercise thermal events play a role in exercise-induced asthma (EIA), nine normal and eight asthmatic subjects on three occasions exercised while they inhaled frigid air. During the recovery period, either cold air, air at room temperature and humidity, or air at body conditions was administered in a random fashion. On a fourth occasion, body-condition air was given during exercise. Pulmonary mechanics were measured before and after each challenge. No changes in mechanics developed when air at body conditions was inhaled during exercise, however, increasing the heat content of the air during recovery produced progressively greater obstruction in both groups. On a separate occasion, seven asthmatics hyperventilated frigid air and either recovered spontaneously or had their ventilation slowly reduced. Controlling ventilation markedly attenuated the obstructive response. These data demonstrate that the severity of EIA is dependent not only on airway cooling but also upon the rapidity and magnitude of airway rewarming postchallenge.
ABC of computing. Word processing.
Authors: A J Asbury
Journal: BMJ (1983)

Word processing is using a computer to manipulate text with the aim of perfecting documents.This type of computing has grown since microprocessors of considerable capacity became available cheaply: it is now one of the major growth points in the computer industry.Some years ago businessmen realised that time and therefore money could be saved if documents did not have to be continually retyped.The text could instead be held and modified in the memory of a computer and, when perfect, passed to a daisywheel printer for the final typing.Since these earlier ideas word processing has developed rapidly to include automatic indexing, spelling checking, typesetting, letter writing, and many other developments.Word processing can be of help to all types of doctor, from the general practitioner who would like to speed the production of his referral letters to the research anaesthetist writing his PhD and the professor writing textbooks.
Pancreatitis in Finland between 1970 and 1989.
Authors: M Jaakkola, I Nordback
Journal: Gut (1993)

The incidence and mortality from pancreatitis in Finland between 1970 and 1989 were studied and compared with the alcohol consumption in the country and with the incidence of liver cirrhosis and gall stone disease. Hospital discharge data were obtained from the Finnish National Agency for Welfare and Health, the causes of deaths from the Finnish State Statistics, and annual alcohol consumption from the Finnish State Alcohol Company. There were 56,353 hospital treatment periods because of pancreatitis. The incidence of pancreatitis discharges increased from 46.6 to 73.4/100,000/year. In men it increased from 59.1 to 113.4, but in women it remained unchanged (mean 35.0). The incidence of pancreatitis discharges correlated with the alcohol consumption in Finland (r = 0.78, p = 0.0001). The incidence of pancreatitis discharges correlated in men, but not in women, with the incidence of liver cirrhosis (r = 0.81, p = 0.0001). In women, but not in men, the incidence of pancreatitis discharges correlated with the incidence of gall stone disease discharges (r = 0.77, p = 0.0001). The incidence of discharges due to haemorrhagic pancreatitis and pancreatic abscess doubled in men and remained unchanged in women. Pancreatitis death rate decreased from 5.9% (men 4.8%, women 7.0%) to 2.6% (men 2.4%, women 2.7%).
A comparative study for the effect between endoscopic treatment with N-butyl-2-cyanoacrylate(histoacryl) injection and transjugular intrahepatic portosystemic shunt(tips) on acute esophagogastric variceal bleeding
Authors: S.J. Kim, J.S. Rew, S.K. Choi, Y.E. Joo, W.S. Lee, C.H. Park, Y.H. Sohn
Journal: Journal of Hepatology (2003)
Silent Ischemia on Holter Monitoring Predicts Mortality in High-Risk Postinfarction Patients
Authors: Sidney O, Gottlieb
Journal: JAMA (1988)

The relative prognostic significance of ischemic ST changes on two-lead continuous electrocardiographic (Holter) monitoring in 103 high-risk postinfarction patients was examined. Ischemic ST changes were detected in 30 patients, with a median number of five episodes per day and median total daily duration of 157 minutes. Only one third of these patients reported any angina in the hospital, and 28 of the 30 patients had silent ST changes on Holter monitoring. The remaining 73 patients had no ischemic ST changes on Holter monitoring. At one year, nine (30%) of 30 patients with ischemic ST changes were dead vs only eight (11%) of 73 patients without such changes. Multivariate Cox's hazard function analysis on 18 variables, including age, type of infarction, Lown and Killip class, ejection fraction, and medications, showed that the presence of ST changes on Holter monitoring was a significant predictive variable for one-year mortality in the overall study population and particularly in the subgroup of 59 patients who could not undergo early exercise treadmill testing. Thus, ischemic ST changes on Holter monitoring, the majority of which are silent, occur in nearly one third of high-risk postinfarction patients and are significantly associated with one-year mortality.
DRUG EEACTIONS XIII
Authors: John Almeyda
Journal: British Journal of Dermatology (1971)

Journal Article DRUG EEACTIONS XIII Get access John Almeyda John Almeyda The London Hospital, E.l Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 84, Issue 3, 1 March 1971, Pages 298–300, https://doi.org/10.1111/j.1365-2133.1971.tb14221.x Published: 01 March 1971
Re: Levels of Hypoxia-Inducible Factor-1 During Breast Carcinogenesis
Authors: A. Costa, D. Coradini, A. Carrassi, R. Erdas, A. Sardella, M. G. Daidone
Journal: JNCI Journal of the National Cancer Institute (2001)

Re: Levels of Hypoxia-Inducible Factor-1␣ During Breast Carcinogenesis Bos et al.(1) reported that hypoxiainducible factor-1␣ (HIF-1␣) protein was undetectable in normal breast tissue and benign breast lesions but was expressed in in situ and invasive breast cancers, with increased levels as dedifferentiation progressed.