tbuckley/cabot-search huggingface dataset:
Function follows form: The structure of the N-terminal domain of HCV NS5A
Authors: Darius Moradpour, Volker Brass, Francois Penin
Journal: Hepatology (2005)

Abstract Hepatitis C virus (HCV) is a human pathogen affecting nearly 3% of the world's population. Chronic infections can lead to cirrhosis and liver cancer. The RNA replication machine of HCV is a multi-subunit membrane-associated complex. The nonstructural protein NS5A is an active component of HCV replicase, as well as a pivotal regulator of replication and a modulator of cellular processes ranging from innate immunity to dysregulated cell growth. NS5A is a large phosphoprotein (56-58 kd) with an amphipathic α-helix at its amino terminus that promotes membrane association. After this helix region, NS5A is organized into 3 domains. The N-terminal domain (domain I) coordinates a single zinc atom per protein molecule. Mutations disrupting either the membrane anchor or zinc binding of NS5A are lethal for RNA replication. However, probing the role of NS5A in replication has been hampered by a lack of structural information about this multifunctional protein. Here we report the structure of NS5A domain I at 2.5-Å resolution, which contains a novel fold, a new zinc-coordination motif, and a disulfide bond. We use molecular surface analysis to suggest the location of protein-, RNA-, and membrane-interaction sites.
Delayed Imaging of the Pelvis With Diluted and Filled Bladder
Authors: Metin Halac, Anar Aliyev, Sabire Yılmaz, Meftune Ozhan, Rana Kaya, Sait Sağer, Nurhan Ergül
Journal: Clinical Nuclear Medicine (2012)

A 53-year-old man with recent diagnosis of urinary bladder carcinoma was referred to our PET/CT unit. There was no sign and symptom other than hematuria. Urinary ultrasound showed a mass lesion at the right wall of the urinary bladder. FDG PET/CT was performed for initial staging. One-hour whole-body PET/CT images were normal, whereas delayed pelvic images with “diluted and filled bladder” demonstrated that intense hypermetabolic lesion at the right lateral wall of the urinary bladder.
BODY FLUID AND ELECTROLYTE COMPOSITION IN ARTERIAL HYPERTENSION. I. STUDIES IN ESSENTIAL, RENAL AND MALIGNANT HYPERTENSION*
Authors: W. Hollander, A. V. Chobanian, B. A. Burrows
Journal: Journal of Clinical Investigation (1961)

In previous studies in this laboratory it was found that the capacity to excrete sodium as indi- cated by the rate of excretion of an intravenously administered sodium load was significantly in- creased in essential and renal hypertension (1,2).Sodium excretory capacity was reduced by antihypertensive therapy and was correlated sig- nificantly with the level of arterial pressure.How- ever, the absence of a high degree of correlation, together with the ability of dietary sodium intake to influence the renal capacity to excrete sodiun-m, suggested that in addition to an elevated blood pressure other factors such as an increase in body sodium and fluid volume might enhance sodium excretion in hypertensive individuals.Studies in Cushing's syndrome and Addison's disease by other workers suggest that the level of adrenal cortical activity may influence not only the renal capacity to excrete sodium but also the arterial pressure as well as the body's content of fluids and electrolytes (3, 4).In line with these observations are recent relports indicating that an increase in aldosterone activity occurs in certain groups of hypertensive subjects (5-7).To clarify the relationship of arterial hypertension to alterations in adrenal cortical function and in electrolyte and water metabolism, it was decided to study body fluid and electrolyte composition in various forms of hypertension, including that as- sociated with primary aldosteronism (8).The present report describes the findings in essential, renal and malignant hypertension.The observa-
The search for the gay gene
Authors: Timothy F Murphy
Journal: BMJ (2005)

A nother study from Dean Hamer's laboratory at the US National Institutes of Health indicates that genes may influence homosexuality in males ( Human Genetics 2005;116: 272-8). The study involved a complete genome scan, the first ever conducted for the study of sexual orientation. Like the others before it, this study is far from conclusive, but it adds to the growing sense that genes play a role in male sexual orientation. The evidence for a genetic contribution to female homosexuality is less well developed, but the case is hardly closed. Social opinion in the back-ground of this research remains divided about its meaning and value.

Some commentators worry that finding genetic aspects to sexual orientation will make things worse for gay men and women around the world. They worry that people will be tested against their will and that clinicians will even test embryos and fetuses. Reacting to the latest genetic study, one Maine legislator proposed an …
HYDROA VACCINIFORME OCCURRING IN ASSOCIATION WITH HARTNUP DISEASE
Authors: PETER J. ASHURST
Journal: British Journal of Dermatology (1969)

Journal Article HYDROA VACCINIFORME OCCURRING IN ASSOCIATION WITH HARTNUP DISEASE Get access PETER J. ASHURST PETER J. ASHURST Department of Dermatology, Royal Infirmary, Aberdeen Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 81, Issue 7, 1 July 1969, Pages 486–492, https://doi.org/10.1111/j.1365-2133.1969.tb16023.x Published: 01 July 1969 Article history Accepted: 14 December 1968 Published: 01 July 1969
Mean glucose level is not an independent risk factor for mortality in mixed ICU patients
Authors: Jack J. M. Ligtenberg, Sofie Meijering, Ymkje Stienstra, Iwan C. C. van der Horst, Mathijs Vogelzang, Maarten W. N. Nijsten, Jaap E. Tulleken, Jan G. Zijlstra
Journal: Intensive Care Medicine (2006)
Effect of health visitors working with elderly patients in general practice: a randomised controlled trial.
Authors: N J Vetter, D A Jones, C R Victor
Journal: BMJ (1984)

Health visitors were employed specifically to care for two years for a random sample of patients in general practice who were aged over 70. Independent assessments made at the beginning and end of the study showed that the health visitor in an urban practice had some impact on her caseload of patients; she provided more services for them, their mortality was reduced, and their quality of life improved, though the last measure just failed to be statistically significant. The health visitor working in a rural practice had no such effect.
STAT proteins – Key regulators of anti-viral responses, inflammation, and tumorigenesis in the liver
Authors: Bin Gao, Hua Wang, Fouad Lafdil, Dechun Feng
Journal: Journal of Hepatology (2012)

Since its discovery in the early 1990s, the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway has been found to play key roles in regulating many key cellular processes such as survival, proliferation, and differentiation. There are seven known mammalian STAT family members: STAT1, 2, 3, 4, 5a, 5b, and 6. In the liver, activation of these STAT proteins is critical for anti-viral defense against hepatitis viral infection and for controlling injury, repair, inflammation, and tumorigenesis. The identification of functions for these STAT proteins has increased our understanding of liver disease pathophysiology and treatments, while also suggesting new therapeutic modalities for managing liver disease.
NEED FOR LATE REINTERVENTIONS IS STRONGLY ASSOCIATED WITH CLASS-3 TECHNICAL PERFORMANCE SCORES (MAJOR RESIDUAL DEFECTS) IN MID AND HIGH COMPLEXITY PROCEDURES
Authors: Meena Nathan, Frank Pigula, Hua Liu, Kimberlee Gauvreau, Steven Colan, Matthew DiOrio, Francis Fynn-Thompson, Sitaram Emani, Christopher Baird, John Mayer, Pedro del Nido
Journal: Journal of the American College of Cardiology (2013)
Oscillometric devices are good in routine practice
Authors: M. R. Nelson
Journal: BMJ (2011)

Placebo (PL) treatment is a method utilized as a control condition in clinical trials. A positive placebo response is seen in up to 50% of patients with Parkinson disease (PD), pain syndromes, and depression. The response is more pronounced with invasive procedures or advanced disease. Physiologic and biochemical changes have been studied in an effort to understand the mechanisms underlying placebo-related clinical improvement. In PD, objective clinical improvements in parkinsonism correlate with dopaminergic activation of the striatum, documented by PET and with changes in cell firings of the subthalamic nucleus documented by single cell recordings. Dopaminergic pathways mediating reward may underlie PL-mediated improvement in PD. In pain syndromes, endogenous opioid release triggered by cortical activation, especially the rostral anterior cingulated cortex, is associated with PL-related analgesia and can be reversed by opioid antagonists. Covert treatment of an analgesic is less effective than overt treatment, suggesting an expectation component to clinical response. In depression, PL partially imitates selective serotonin reuptake inhibitor–mediated brain activation. Diseases lacking major “top-down” or cortically based regulation may be less prone to PL-related improvement.
Pediatric Drug Labeling
Authors: Rosemary Roberts, William Rodriguez, Dianne Murphy, Terrie Crescenzi
Journal: JAMA (2003)

Approximately 50% to 75% of drugs used in pediatric medicine have not been studied adequately to provide appropriate labeling information. In 1997, Congress passed the Food and Drug Administration Modernization Act (FDAMA), which encouraged pediatric drug development by providing an incentive in the form of additional marketing exclusivity.To identify new drug labeling information from pediatric studies submitted to the FDA in response to written requests.Between July 1998 and April 1, 2002, the FDA requested studies on 242 drugs, and 53 drugs were granted exclusivity. As of January 2003, 49 drugs have new labels. Data from the studies of the first 33 drugs with new pediatric information on the label as of April 2002 are included. Significant labeling information was analyzed along with baseline data and types of studies requested.Safety data and pediatric information for labeled drugs.There were 53 studies for 33 drug products, 12 (23%) were evaluated for safety only; 23 (43%), safety and efficacy; and 18 (34%), pharmacokinetics and/or pharmacodynamics. Significant new dosing and/or safety information was identified for 12 (36%) drugs. New dosing information was determined for 7 of these drugs. Safety information was defined for gabapentin, propofol, sevoflurane, the combination of ribavirin and interferon alfa-2b, and various betamethasone-containing dermatologic preparations. There was a higher percentage of deaths reported with patients who received propofol compared with controls in the pediatric intensive care unit. Seizures were seen in patients administered sevoflurane. Patients receiving a combination of ribavirin and interferon alfa-2b experienced an increased incidence of suicidal ideation when compared with adults. An unexpectedly high percentage of those receiving betamethasone-containing dermatologic preparations had documented hypopituitary-adrenal axis suppression.The FDAMA has stimulated pediatric clinical studies resulting in improved understanding of the pharmacokinetics of drugs prescribed in pediatric medicine, important dose changes, and improved safety for children taking certain drugs.
Combined Alpha and Beta Sympathetic Blockade in Hyperthyroidism
Authors: BILL DEAN STOUT
Journal: Annals of Internal Medicine (1969)

Clinical and metabolic effects of propranolol (4.6 to 10.3 mg/kg/day) and phenoxybenzamine hydrochloride (0.44 to 0.82 mg/kg/day) administered for an average of 71 days were studied in eight hyperthyroid patients. Body weight, oxygen consumption, kinemometric measurements of the Achilles reflex, and serum lipids (cholesterol, triglycerides, and phospholipids) were studied. Common thyroid function tests, including protein-bound iodine, 131I uptake, resin triiodothyronine uptake, and 131I scan of the thyroid gland, were made before and after treatment. Five normal male subjects (mean age, 22 years) given propranolol (3.2 to 5.0 mg/kg/day) and phenoxybenzamine hydrochloride (0.3 to 0.47 mg/kg/day) served as controls for oxygen consumption and Achilles reflex studies. The drugs altered the thyrotoxic findings toward normal in the following manner: mean oxygen consumption reduced -12% (P < 0.01); significant increase of Achilles reflex times (P < 0.01); mean weight gain of 9 lb or +7% (P < 0.03); and most of the common signs and symptoms of thyrotoxicosis eliminated or attenuated. No effects on serum lipids or thyroid function tests were observed. It is concluded that alpha and beta adrenergic receptor blocking agents attenuate the weight loss, increased oxygen consumption, reflex changes, and most signs and symptoms of thyrotoxicosis. Furthermore, these abnormalities of hyperthyroidism are mediated in part via the sympathetic nervous system. This form of therapy is effective as an adjunct in the interim management of thyrotoxicosis.
Anorexia nervosa: a Case Study
Authors: Richard L. Steele
Journal: Psychotherapy and Psychosomatics (1976)

D.R., a single 19-year-old female experiencing anorexia nervosa, was admitted to a mental health center inpatient unit weighing 64 lb, approximately 54 lb underweight, with liver, kidney, and pancreas damage. D.R. was hospitalized for 59 days. Treatment consisted of utilizing a hierarchy of reinforcements in the form of privileges mutually agreed upon between patient and therapist, psychodynamic and supportive psychotherapy, and involvement in the ward milieu therapeutic program. All privileges had to be earned. Access to food was controlled by the staff. For pounds gained privileges were granted, for pounds lost privileges were curtailed. Dynamically, D.R.'s eating behavior was viewed as an unconscious spite and revenge reaction toward her parents as well as an attempt to elicit attention. At the time of discharge D.R. weighed 104.5 lb. Prior to discharge D.R. agreed that if her weight dropped below 100 lb she would return for readmission. Five months later D.R/s weight stabilized between 102 and 104 lb. Two years later, D.R.'s weight remains at that level. The study cautions against using solely a behavior modification approach in the treatment of anorexia nervosa.
Antigen-specific Tregs control T cell responses against a limited repertoire of tumor antigens in patients with colorectal carcinoma
Authors: Andreas Bonertz, Jürgen Weitz, Dong-Ho Kim Pietsch, Nuh N. Rahbari, Christoph Schlude, Yingzi Ge, Simone Juenger, Israel Vlodavsky, Khashayarsha Khazaie, Dirk Jaeger, Christoph Reissfelder, Dalibor Antolovic, Maximilian Aigner, Moritz Koch, Philipp Beckhove
Journal: Journal of Clinical Investigation (2009)

Spontaneous antitumor T cell responses in cancer patients are strongly controlled by Tregs, and increased numbers of tumor-infiltrating Tregs correlate with reduced survival. However, the tumor antigens recognized by Tregs in cancer patients and the impact of these cells on tumor-specific T cell responses have not been systematically characterized. Here we used a broad panel of long synthetic peptides of defined tumor antigens and normal tissue antigens to exploit a newly developed method to identify and compare ex vivo the antigen specificities of Tregs with those of effector/memory T cells in peripheral blood of colorectal cancer patients and healthy subjects. Tregs in tumor patients were highly specific for a distinct set of only a few tumor antigens, suggesting that Tregs exert T cell suppression in an antigen-selective manner. Tumor-specific effector T cells were detectable in the majority of colorectal cancer patients but not in healthy individuals. We detected differences in the repertoires of antigens recognized by Tregs and effector/memory T cells in the majority of colorectal cancer patients. In addition, only effector/memory T cell responses against antigens recognized by Tregs strongly increased after Treg depletion. The selection of antigens according to preexisting T cell responses may improve the efficacy of future immunotherapies for cancer and autoimmune disease.
Two Immunologic Reactions in the Pathogenesis of Hepatitis?
Authors: Fiorenzo Paronetto, Hans Popper
Journal: New England Journal of Medicine (1976)

Two unsolved problems interfere with the rational management of hepatitis. One is ignorance about the pathogenesis of hepatic necrosis and the other is the lack of information about why some cases of acute hepatitis heal and others proceed to chronic hepatitis and cirrhosis. The first unsolved problem deprives the patient of a rational therapy for the damaged liver cell, and the second offers difficulties in prognosis. Immunologic processes are incriminated in hepatocellular necrosis and in the explanation of chronicity of hepatitis.In 1908 Fiessinger postulated, "To defend itself against intoxication from tissue breakdown products, the organism forms antibodies which increase . . .
The Phonocardiographic Differentiation of Pulmonic and Aortic Insufficiency
Authors: ROBERT H. SCHWAB, JOHN H. KILLOUGH
Journal: Circulation (1965)

A phonocardiographic technic for differentiating the murmurs of aortic and pulmonic insufficiency is described. Four patients with diastolic "decrescendo" murmurs are presented to illustrate this technic.
Self-monitoring of blood glucose was not cost-effective in non–insulin-treated type 2 diabetes
Authors: Sumit R. Majumdar
Journal: Annals of Internal Medicine (2008)

Source Citation Simon J, Gray A, Clarke P, et al. Cost effectiveness of self monitoring of blood glucose in patients with non-insulin treated type 2 diabetes: economic evaluation of data from the DiGEM trial. BMJ. 2008;336:1177-80. 18420663
Effects of Increasing Frequency of Contraction on the Force Velocity Relation of Left Ventricle
Authors: J. W. Covell, J. Ross, R. Taylor, E. H. Sonnenblick, E. Braunwald
Journal: Cardiovascular Research (1967)

Journal Article Effects of Increasing Frequency of Contraction on the Force Velocity Relation of Left Ventricle Get access James W. Covell, James W. Covell From the Cardiology Branch, National Heart Institute, Bethesda, Maryland, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar John Ross, Jr., John Ross, Jr. From the Cardiology Branch, National Heart Institute, Bethesda, Maryland, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar Roger Taylor, Roger Taylor From the Cardiology Branch, National Heart Institute, Bethesda, Maryland, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar Edmund H. Sonnenblick, Edmund H. Sonnenblick From the Cardiology Branch, National Heart Institute, Bethesda, Maryland, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar Eugene Braunwald Eugene Braunwald From the Cardiology Branch, National Heart Institute, Bethesda, Maryland, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 1, Issue 1, January 1967, Pages 2–8, https://doi.org/10.1093/cvr/1.1.2 Published: 01 January 1967 Article history Received: 11 October 1966 Published: 01 January 1967
Bronchial reactivity to histamine before and after sodium cromoglycate in bronchial asthma.
Authors: B Kang, R G Townley, C K Lee, B Miller Kolotkin
Journal: BMJ (1976)

Out of 19 patients with extrinsic bronchial asthma challenged with 123 mug histamine acid phosphate by intravenous infusion only 13 responded with a fall in FEV1 of over 10% (mean 16%). Seventeen of these patients were given histamine 2 mg/ml by aerosol, and all responded with a mean decrease in FEV1 of 37.8%. When challenged with allergen extract by aerosol the mean decrease in FEV1 was 37.5%. After 40 mg sodium cromoglycate 15 of the 17 patients showed significant protection against allergen challenge with a mean decrease in FEV1 of only 23.6%. Inhalation of 40 mg sodium cromoglycate, however, failed to protect against histamine given by either the intravenous or aerosol route. Histamine given intravenously to asthmatic patients produces less of a bronchial response than when given by aerosol, even though the intravenous route produces many more systemic symptoms, such as flushing and throbbing headache. The protection of sodium cromoglycate against an allergen inhalation challenge is not due to histamine antagonsim.
Synthesis and release of Hageman factor (Factor XII) by the isolated perfused rat liver.
Authors: H Saito, S M Hamilton, A S Tavill, L T Goodnough, L Louis, A Angell
Journal: Journal of Clinical Investigation (1983)

The site of synthesis of Hageman factor (HF, Factor XII) has not been previously demonstrated with certainty. We have studied the production and release of HF in the isolated perfused rat liver and have compared rates of synthesis in this system with absolute rates of degradation measured in vivo. Rat livers, perfused for 5 h with a recycling fluid consisting of a perfluorochemical emulsion (Fluosol 43), were used to demonstrate a cumulative increase of HF in the perfusate as measured by a specific and sensitive radioimmunoassay. The rate of increase in the perfusate pool of HF during the final 4 h of perfusion yielded a mean synthetic rate of 3.5 micrograms/h per 100 g body wt, which was approximately 0.2% of the synthetic rate of albumin in the same system. The cumulative appearance of albumin and transferrin was linear after 1 h and calculated rates of synthesis were 2,012 micrograms/h per 100 g and 263 micrograms/h per 100 g body wt, respectively. De novo synthesis of HF was confirmed by demonstrating incorporation of [14C]lysine into specific immunoprecipitates of HF, and by the observations that both specific incorporation of labeled amino acid and net release of immunoassayable HF were inhibited by the administration of cycloheximide. Finally, it was evident that the rates of synthesis observed in the isolated perfused liver agreed closely with absolute rates of degradation of HF measured in vivo with 125I-rat HF (4.0 micrograms/h per 100 g). From these data we conclude that the liver is the principal site of synthesis of HF.
Preventing the Emergence of Antimicrobial Resistance
Authors: Benjamin Schwartz
Journal: JAMA (1997)

The emerging global problem of antimicrobial resistance has multiple aspects and involves multiple pathogens. One common theme is that antimicrobial drug use exerts selective pressure favoring the emergence of resistance. Strategies to prevent the development and spread of antimicrobial resistance depend on the pathogens. For bacterial respiratory tract pathogens (eg,<i>Streptococcus pneumoniae</i>), controlling outpatient antimicrobial use is crucial<sup>1-3</sup>; for some enteric pathogens (eg,<i>Salmonella</i>), limiting antimicrobial use in animals is important<sup>4,5</sup>; and, for pathogens that cause nosocomial infections, improving inpatient antimicrobial use and infection control practices is necessary.<sup>6</sup>Addressing antimicrobial use and resistance is one of the most urgent priorities in confronting emerging infectious disease threats.<sup>7,8</sup> See also p 901. Respiratory infections account for more than three quarters of the antimicrobial drug prescriptions written annually in physicians' offices.<sup>9</sup>In this issue of<i>JAMA</i>, Gonzales et al<sup>10</sup>identify antibiotic prescribing for adults with colds, nonspecific