tbuckley/cabot-search huggingface dataset:
Treating hepatitis C: Can you teach old dogs new tricks?
Authors: Charles M. Rice, Shihyun You
Journal: Hepatology (2005)

Viruses depend on host-derived factors for their efficient genome replication. Here, we demonstrate that a cellular peptidyl-prolyl cis-trans isomerase (PPIase), cyclophilin B (CyPB), is critical for the efficient replication of the hepatitis C virus genome. CyPB interacted with the HCV RNA polymerase NS5B to directly stimulate its RNA binding activity. Both the RNA interference (RNAi)-mediated reduction of endogenous CyPB expression and the induced loss of NS5B binding to CyPB decreased the levels of HCV replication. Thus, CyPB functions as a stimulatory regulator of NS5B in HCV replication machinery. This regulation mechanism for viral replication identifies CyPB as a target for antiviral therapeutic strategies.
Macromolecule adducts as biomarkers of exposure to environmental mutagens in human populations.
Authors: L Ehrenberg, F Granath, M Törnqvist
Journal: Environmental Health Perspectives (1996)

A cancer epidemiologist recently said that "adduct measurement has so far been of little use to epidemiological research." This remark gives us a starting point for the discussion of the purposes of measuring macromolecule adducts that originate from electrophilic compounds or metabolites in humans and animals. Historically, methods for adduct monitoring were developed as a means of determining target doses that, combined with measurements of genotoxic potencies, could be used for risk assessment. With mass spectrometric methods, adducts can be quantified at levels that are thousands of times lower than those in which the cancer incidence associated with this exposure is detectable in disease-epidemiological studies. Furthermore, mass spectrometric techniques permit identification of the chemical structure of the adduct, particularly in the case of hemoglobin adducts. Adduct measurement therefore constitutes not only a means of risk estimation but it may be used as a complement of disease epidemiology in situations in which, for statistical reasons, the risk is too low to be detectable--which does not signify that the risk is acceptably low. It also gives a possibility of identification of the dangerous components in mixed exposures and of the relevant reactive intermediates in cases of complex metabolism.
Effect of sialoadenectomy and synthetic human urogastrone on healing of chronic gastric ulcers in rats.
Authors: P S Olsen, S S Poulsen, K Therkelsen, E Nexo
Journal: Gut (1986)

The effect of extirpation of the submandibular glands, an exocrine organ for epidermal growth factor/urogastrone (EGF/URO), and the effect of oral administration of synthetic human (EGF/URO) on healing of chronic gastric ulcers in rats has been investigated. Removal of the submandibular glands delayed healing of chronic gastric ulcers when examined after 50, 100, and 200 days. Oral administration of synthetic human EGF/URO stimulated gastric ulcer healing when examined after 25 and 50 days of treatment. The effect of synthetic human EGF/URO was comparable with that of cimetidine. The combined administration of synthetic human EGF/URO and cimetidine further increased healing of gastric ulcers compared with administration of each substance. Neither synthetic human EGF/URO, nor removal of the submandibular glands had any influence on gastric acid secretion. This study showed that the submandibular glands influence healing of chronic gastric ulcers and suggest that EGF/URO participate in healing of chronic gastric ulcers in rats.
Osteoarthritis of the hip and acetabular dysplasia.
Authors: P Croft, C Cooper, C Wickham, D Coggon
Journal: Annals of the Rheumatic Diseases (1991)

The relation between acetabular dysplasia and osteoarthritis of the hip was examined in a series of 1516 pelvic radiographs taken for non-skeletal indications. Osteoarthritis was assessed by measuring joint space, and dysplasia by the centre-edge angle and acetabular depth. In contrast with previous studies of patients with symptomatic osteoarthritis of the hip, no evidence that dysplasia predisposes to osteoarthritis was found. Possible reasons for the discrepancy are discussed. It was concluded that although acetabular dysplasia may lead to osteoarthritis of the hip in some subjects, it is unlikely to be an important cause of the disease in men.
Physician Payment Incentives to Improve Care Quality—Reply
Authors: Naomi S. Bardach, Sarah C. Shih, R. Adams Dudley
Journal: JAMA (2014)

Drs Himmelstein and Woolhandler suggest that pay-for-performance incentives led clinicians to falsify records. The program we evaluated was designed to align incentives with delivering high-quality care, rather than high-volume care, which is the incentive alignment under fee-for-service, and to pay clinicians more for doing what is difficult, such as controlling blood pressure in a patient with comorbidities.

We have no data specifically on falsification. However, prior literature on Healthcare Effectiveness Data and Information Set measures found that clinicians generally round to the nearest number on a 10 scale (ie, round to 130 mm Hg for a systolic blood pressure measurement of 129 mm Hg or 131 mm Hg).1 In reviewing data from our practices abstracted by a third party,2 we found this rounding behavior in both study groups. Of 1651 visits reviewed, among systolic blood pressure measurements ranging from 129 to 131 mm Hg, the control group (n = 141) percentages for readings were 4.2% at 129 mm Hg, 93.0% at 130 mm Hg, and 2.8% at 131 mm Hg, and in the incentive group (n = 116), they were 1.7%, 91.3%, and 6.9%, respectively.
Abstract IA22: Targeting histone modifying enzymes in leukemia
Authors: Scott A. Armstrong
Journal: Cancer Research (2014)

Abstract Leukemias harboring rearrangements of the MLL gene carry a poor prognosis. Recently, it has become increasingly clear that MLL-fusion proteins induce widespread epigenetic deregulation that may mediate much of their transforming activity. The histone methyltransferase DOT1L, which methylates histone 3 on lysine 79 (H3K79), has received particular attention. Several MLL-fusion proteins physically interact with DOT1L. Genome-wide H3K79 methylation profiles in MLL-rearranged leukemias are abnormal, and can serve to distinguish MLL-rearranged from other types of leukemias. Mechanistic studies have demonstrated that MLL-fusion proteins subvert a normal gene regulatory mechanism through aberrant hyperconversion of H3K79 methylation to higher methylated states at critical oncogenic targets including the HoxA cluster genes and Meis1. Remarkably, genetic inactivation or small molecule inhibition of DOT1L and thus H3K79 methylation affects expression of MLL-target loci and is detrimental to the leukemogenic activity of MLL-rearranged cells, thus demonstrating that transformation in these leukemias is driven by a DOT1L dependent, aberrant epigenetic program. Clinical trials of small molecule DOT1L inhibitors are in phase 1 clinical trials. Recent studies on the roles for DOT1L and H3K79 methylation in MLL-rearranged leukemias will be discussed. Citation Format: Scott A. Armstrong. Targeting histone modifying enzymes in leukemia. [abstract]. In: Proceedings of the AACR Special Conference on Pediatric Cancer at the Crossroads: Translating Discovery into Improved Outcomes; Nov 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;74(20 Suppl):Abstract nr IA22.
Successful treatment of toenail mycosis with terbinafine and itraconazole gives long term benefits
Authors: M Brautigam, G Weidinger, S Nolting
Journal: BMJ (1998)

EDITOR —In 1995 we published a study comparing treatments with terbinafine and itraconazole for tinea infection of the toenail.1 Three years after the end of our one year study we carried out a follow up assessment in the patients who were cured. The study was double blind and assessed 26 patients from the terbinafine group and 21 patients from the itraconazole group. All patients had cured target nails, and none had applied …
Gene Linked to ALS
Authors: Tracy Hampton
Journal: JAMA (2007)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Prospective Analysis of Mortality, Morbidity, and Risk Factors in Elderly Diabetic Subjects
Authors: Masafumi Katakura, Motoji Naka, Teruki Kondo, Nakako Nishii, Mitsuhisa Komatsu, Yoshihiko Sato, Keishi Yamauchi, Kunihide Hiramatsu, Mitsuru Ikeda, Toru Aizawa, Kiyoshi Hashizume
Journal: Diabetes Care (2003)

To clarify mortality and morbidity of intensively managed elderly diabetic individuals and to explore factors predicting mortality and diabetes-related end points.A total of 390 elderly (>or=65 years of age) outpatients with type 2 diabetes ( 173 men and 217 women, mean age 73.0 years) were analyzed. The mean HbA(1c) upon entry was 6.8% (332 receiving oral hypoglycemics and/or insulin) and blood pressure upon entry was 136/74 mmHg (219 receiving antihypertensive drugs). The patients have been followed-up for 3 years with HbA(1c) <7.0% and blood pressure <145/80 mmHg as targets, with mortality and an aggregate of fatal and nonfatal diabetes-related events as end points. Mortality rate and causes of mortality, as well as risk factors for mortality and morbidity, were determined.The mortality rate, 2.9% per year, was comparable to that of the age- and sex-matched general population. Stroke was a leading cause of mortality after malignancy. By the univariate Cox proportional hazards model, only high serum creatinine and prior stroke were highly significant and strong risks for both end points. In those without prior stroke and receiving antihypertensive agents, the incidence of the diabetes-related end point based on their systolic blood pressure (SBP) quartile was U-shaped, with the nadir at the 3rd (SBP, 137-147 mmHg) and the peak at the 1st (SBP <or= 125 mmHg) quartile.In well-controlled elderly diabetic subjects, there was no excessive mortality compared to the age- and sex-matched general population. Renal dysfunction and prior stroke were independent risks for mortality and morbidity. In those without prior stroke, a risk of too much lowering of blood pressure was suggested.
Lack of beta-adrenoreceptor hypersensitivity after abrupt withdrawal of long-term therapy with oxprenolol.
Authors: P Bolli, F R Bühler, E A Raeder, F W Amann, M Meier, H Rogg, D Burckhardt
Journal: Circulation (1981)

The possibility of beta-adrenoreceptor hypersensitivity after abrupt withdrawal of long-term therapy (8-18 months) with the slow-release (SR) formulation of oxprenolol (160-320 mg/day) was assessed in six patients with uncomplicated essential hypertension. The chronotropic dose 25 of isoproterenol (the dose that increases the resting heart rate by 25 beats/min), plasma concentration of catecholamines, triiodothyronin and thyroxin, plasma renin activity and aldosterone, hemoglobin, hematocrit and oxyhemoglobin dissociation were measured on the last day of oxprenolol SR intake and 1, 2, 3, 6 and 13 days after abrupt replacement by identical placebo tablets. The chronotropic dose 25 of isoproterenol (microgram/m2), which was greater than 25.6 in all patients on the last day of oxprenolol SR, fell to 4.83 +/- 2.03 on the second day and to 3.50 on the third day after its abrupt withdrawal and reached a minimal value on the thirteenth day (2.78 +/- 0.30). Throughout the study, plasma concentrations of catecholamines, triiodothyronin and thyroxin and oxyhemoglobin dissociation remained unchanged. Plasma renin activity and plasma aldosterone, which were suppressed during oxprenolol administration, rose significantly during placebo, coinciding with a significant fall in hematocrit and hemoglobin. No major subjective symptoms were reported by the patients. Thus, hypersensitivity of beta-adrenoreceptor-mediated responses was not demonstrated after sudden withdrawal of oxprenolol SR.
New Initiative for Global TB Control
Authors: Rebecca Voelker
Journal: JAMA (1995)

AN INTERNATIONAL group of experts has developed a set of recommendations for the global control of tuberculosis (TB), while lashing out at governments and pharmaceutical companies for ignoring the world's top infectious disease killer. Their strategy reiterates the importance of completed chemotherapy as a means to cure TB and prevent its spread. The broad-based recommendations note the promise of molecular techniques in new drug and vaccine development, as well as the roles that patient and physician behavior play in controlling the disease. But TB also is a highly political disease, experts stressed during a 2-day conference in Washington, DC, where they finalized the recommendations. London, England—based medical journal<i>The Lancet</i>sponsored the meeting and published the recommendations in its September 23 issue. The politics of TB have been evident in the United States for more than two decades, said Lee B. Reichman, MD, MPH, executive director of the New Jersey
642 INDIVIDUALIZED TREATMENT DURATION WITH PEGINTERFERON-ALFA-2B AND RIBAVIRIN FOR 24, 30 OR 36 WEEKS IN HCV GENOTYPE1-INFECTED PATIENTS WITH UNDETECTABLE HCV-RNA EARLY DURING THERAPY (INDIV-2 STUDY)
Authors: C. Sarrazin, S. Schwendy, B. Möller, N. Dikopoulos, P. Buggisch, J. Encke, G. Teuber, T. Goeser, R. Thimme, H. Klinker, W.O. Boecher, E. Schulte-Frohlinde, R. Prinzing, T. Berg, S. Zeuzem
Journal: Journal of Hepatology (2009)
Polarised light microscopy: principles and practice for the rheumatologist.
Authors: J Chayen
Journal: Annals of the Rheumatic Diseases (1983)

<b>Introduction:</b> In Chronic Obstructive Pulmonary Disease (COPD) inhalation medication plays a key role and correct inhalation technique is crucial. <b>Aim:</b> To evaluate a sample of COPD patients with respect to inhalation technique and the guidance provided by different test methods as well as the need for changing device/inhaler. <b>Methods:</b> In a pilot study we examined 54 COPD patients (30 males) with a mean age of 71.1 (49-92). 16 (29.6%) were newly referred. We collected clinical data (lung function, smoking status etc.). A COPD-nurse tested the inhalation technique: 1) In-checkTM Dial, 2) Turbohaler test-flute, AstraZeneca®, 3) Vitalograph AIMTM (Aerosol Inhalation Monitor), 4) Relevant placebo inhaler, and ended with a final inhaler recommendation - based on the test results. <b>Results:</b> 35.2% (n=19) of the patients demonstrated inspiratory flow ≤ 60 with In-checkTM Dial. 59.3% (n=32) demonstrated insufficient force and/or peak-velocity with the Turbohaler test-flute, AstraZeneca®. Among relevant cases, Vitalograph AIMTM demonstrated insufficient technique in 37 out of 88 (41.6%) with powder and soft mist whereas 0 out of 18 was evaluated to take spray correctly. Based on placebo devices only 37 out of 83 (44.6%) could demonstrate sufficient device handling skills. In total 55.6% (n=30) of the patients were changes in inhalation medication based on the tests. <b>Conclusion:</b> A surprisingly small amount of people treated for COPD were able to demonstrate adequate inhaler skills. There was no correlation between poor skills and being newly referred. More than half of the patients cannot use the inhaler they already have and needs to be changes.
Pharmacological abnormalities in atopic dermatitis
Authors: JON M. HANIFIN
Journal: Allergy (1989)

Numerous investigations have described cutaneous and systemic physiological and pharmacological aberrations in atopic dermatitis and the atopic diathesis. Some of these studies set the stage for a focus upon cyclic nucleotide abnormalities. Elevated leukocyte cyclic AMP-phosphodiesterase accounts for low intracellular cyclic AMP levels in atopic dermatitis. The resultant permissive effect correlates with abnormal functional parameters such as increased basophil histamine release and in vitro IgE synthesis. In vitro and clinical use of phosphodiesterase inhibitors corrects abnormal parameters and may indicate future therapeutic directions.
Psychosocial Impact of Acquired Immune Deficiency Syndrome
Authors: Howard Holtz, Jeffrey Dobro, Robert Palinkas, Rajendra Kapila, James Oleske
Journal: JAMA (1983)

<h3>To the Editor.—</h3> Noticeably absent in the flurry of publications about the current epidemic of acquired immune deficiency syndrome (AIDS) is reference to the psychosocial impact of this devastating new syndrome. In the course of our study and treatment of patients with AIDS, we are finding a mounting array of social problems. Our initial group of patients has had to cope with the collapse of their social support systems and drainage of their financial resources. We hope to avoid this in future patients by heightening awareness of the problem and encouraging greater attention to their continuing needs. We find that a large portion of our AIDS population is indigent and unable to obtain the requisite outpatient care. In an ongoing investigation at our institution, many patients studied thus far have shown evidence of protein-calorie malnutrition and multiple vitamin deficiencies. Once discharged, they can neither eat well enough to bolster their
CUTANEOUS POLYARTERITIS NODOSA
Authors: PETER BORRIE
Journal: British Journal of Dermatology (1972)

Summary.— The case histories of 102 consecutive patients suffering from polyarteritis nodosa were reviewed. The 17 patients with skin lesions were personally examined and investigated. Thirteen were found to have polyarteritis affecting the skin. In one of these cutaneous involvement occurred only 4 days before death and 5 weeks after the onset of the illness. The other 12 showed remarkably similar clinical and pathological features and, together with 3 cases from another hospital, are described in detail. Only the skin, skeletal muscles and peripheral nerves were involved. No deaths have occurred to date (longest follow-up period 23 years), and the disease is now either entirely quiescent or represented only by occasional cutaneous lesions. It is concluded that about 10% of all cases of polyarteritis nodosa, and 30% of those proven histologically, are of this benign type and that this variety can be easily recognized clinically.
Human Anaplastic Thyroid Carcinoma Cells Are Sensitive to NK Cell–Mediated Lysis via ULBP2/5/6 and Chemoattract NK Cells
Authors: Erik Wennerberg, Aline Pfefferle, Lars Ekblad, Yuya Yoshimoto, Veronika Kremer, Vitaliy O Kaminskyy, C Christofer Juhlin, Anders Höög, Inger Bodin, Vitalijs Svjatoha, Catharina Larsson, Jan Zedenius, Johan Wennerberg, Andreas Lundqvist
Journal: Clinical Cancer Research (2014)

Anaplastic thyroid carcinoma (ATC) is one of the most aggressive forms of cancer with no curative therapies available. To date, strategies to target ATC by immunotherapy have not been evaluated. We investigated whether ATC would be a suitable target for natural killer (NK) cell-based immunotherapy.We first established seven new cell lines from ATC tumors, three from papillary thyroid carcinoma tumors and analyzed them together with eight additional ATC cell lines. Cells were analyzed for sensitivity to lysis by NK cells and their ability to chemoattract and regulate the activity of NK cells. In addition, fresh tumor samples and peripheral blood from six patients with ATC were analyzed for NK cell infiltration and phenotype.We observed that ATC cell lines are sensitive to lysis by ex vivo expanded NK cells and that the lysis was abrogated upon blockade of NKG2D. Sensitivity of thyroid cancer cell lines to NK cell-mediated lysis correlated with surface expression of UL16-binding protein 2 on tumor cells. Moreover, ATC cell lines produced high levels of CXCL10 and stimulated migration of expanded NK cells and ATC tumors were enriched for NK cells expressing the cognate chemokine receptor CXCR3. However, compared with NK cells in peripheral blood, ATC tumor-derived NK cells displayed a suppressed phenotype with a downregulated expression of NKG2D. In vitro, suppression of NK cell-mediated lysis and NKG2D expression by ATC cells was restored upon neutralization of prostaglandin-E2.ATC cell lines are sensitive to NK cell-mediated lysis via ULBP2/5/6 and chemoattract CXCR3-positive NK cells. Patients with ATC may benefit from NK cell-based immunotherapy.
Drug Control of Diuretic-Induced Hyperuricemia
Authors: Albert N. Brest
Journal: JAMA (1966)

ORAL SULFONAMIDE diuretics are the mainstays of the current diuretic armamentarium. In addition to the thiazide derivatives, other potent oral sulfonamide diuretics, including phthalimidine and quinazoline drugs, are currently available. The untoward reactions which may be encountered with these various compounds include electrolyte disequilibriums, systemic idiosyncratic reactions, and metabolic alterations. The last-named include azotemia, hyperglycemia, hyperammoniemia, and hyperuricemia. The purpose of this communication is to describe the frequency, significance, and control of hyperuricemia induced by the quinazoline diuretic quinethazone.  The reported incidence of hyperuricemia during oral-sulfonamide-diuretic therapy has varied widely, ranging from 1% to 75%. 1,2 This extreme variability probably reflects differences in patient selection, frequency with which serum-uric-acid determinations have been performed, and, possibly, diet. In addition to primary gout, such diverse organic illnesses as coronary-artery disease, diabetes mellitus, and renal disease may affect serum-uricacid levels. Hence the type of patient population will significantly influence the reported findings.  Abundant
Evolution of mating strategies: Evidence from the fossil and archaeological records
Authors: Steven Mithen
Journal: Behavioral and Brain Sciences (2000)

Gangestad &amp; Simpson provide a persuasive argument that both men and women have evolved conditional mating strategies. Their references to “ancestral” males and females are rather vague, which is unfortunate, as they seek to justify their arguments by invoking human evolutionary history. When one actually examines the evidence for human evolution further, more support for their arguments can be found, as predominant types of mating strategies are likely to have shifted in light of environmental and anatomical developments. We can also see in the archaeological record evidence for a further dimension of strategic pluralism – the use of material culture to advertise good genes in some species of ancestral males.
Indication of liver transplantation in severe alcoholic liver cirrhosis: quantitative evaluation and optimal timing
Authors: Bartholomeus Johannes Veldt, Fabrice Lainé, Anne Guillygomarc'h, Laurence Lauvin, Karim Boudjema, Michel Messner, Pierre Brissot, Yves Deugnier, Romain Moirand
Journal: Journal of Hepatology (2002)