tbuckley/cabot-search huggingface dataset:
Evidence for human leukocyte antigen heterozygote advantage against hepatitis C virus infection
Authors: Peter Hraber, Carla Kuiken, Karina Yusim
Journal: Hepatology (2007)

Outcomes of infection with hepatitis C virus (HCV) vary widely, from asymptomatic clearance to chronic infection, leading to complications that include fibrosis, cirrhosis, hepatocellular carcinoma, and liver failure. Previous studies have reported statistical associations between human leukocyte antigen (HLA) heterozygosity and favorable outcomes of infection with either hepatitis B virus (HBV) or human immunodeficiency virus (HIV) (the “heterozygote advantage”). To investigate whether HLA zygosity is associated with outcome of HCV infection, we used data from the United States Organ Procurement and Transplantation Network database of 52,435 liver transplant recipients from 1995 through 2005. Of these, 30,397 were excluded for lack of HLA data, retransplantation, known HIV infection, or insufficient information regarding HBV infection. The remaining cases were analyzed for associations between HCV infection and HLA zygosity with 1-sided Fisher's exact tests. Results show significantly lower proportions of HLA-DRB1 heterozygosity among HCV-infected than uninfected cases. The differences were more pronounced with alleles represented as functional supertypes ( P = 1.05 × 10−6) than as low-resolution genotypes ( P = 1.99 × 10−3). No significant associations between zygosity and HCV infection were found for other HLA loci. Conclusion: These findings constitute evidence for an advantage among carriers of different supertype HLA-DRB1 alleles against HCV infection progression to end-stage liver disease in a large-scale, long-term study population. Considering HLA polymorphism in terms of supertype diversity is recommended in strategies to design association studies for robust results across populations and in trials to improve treatment options for patients with chronic viral infection. Access to deidentified clinical information relating genetic variation to viral infection improves understanding of variation in infection outcomes and might help to personalize medicine with treatment options informed in part by human genetic variation. (Hepatology 2007.)
"CHRONIC RECURRING MEMBRANOUS PHARYNGITIS."
Authors: JOHN O. McREYNOLDS
Journal: JAMA (1899)

The literature on this subject is so limited, and reports of well-authenticated cases so few in number that I shall pass at once to the brief description of this case in the hope that discussions will follow that will contribute something to our knowledge of this disease. Sir Morell Mackenzie seems to have had by far the most extensive acquaintance with this subject and his experience with it covered a period of only about two years, and nothing was found that had any material effect on the progress of the malady, although his cases without exception recovered. The name which he gives to the trouble is chronic diphtheria, but it differs so widely from ordinary diphtheria in its clinical history and its microscopic findings, that I would suggest the name "chronic recurring membranous pharyngitis," until a more accurate knowledge of the subject can be obtained. The patient, who is now
Influence of electrogenic Na/Ca exchange on the action potential in human heart muscle
Authors: V. J A Schouten, H. E D J ter Keurs, J. M Quaegebeur
Journal: Cardiovascular Research (1990)

Study objective – The plateau of the action potential in heart muscle is largely due to the inward Ca2+ current, ica; however, Ca2+ extrusion via Na+/Ca2+ exchange may also generate a significant current, ina/ca. The aim was to assess the influence of ina/ca on the action potential in isolated human heart muscle. Design – Action potentials and force of isometric contractions were recorded in ventricular trabeculae. The muscle was subjected to various stimulus patterns, Ca2+ antagonists, and variations in the ionic composition of the extracellular medium. Patients – From 49 patients, aged 0.5 to 14 years, small right ventricular trabeculae were obtained during open heart surgery. The operations concerned corrections of ventricular septal defects. Data presented in this paper were from nine preparations in which action potentials were recorded during several hours. Measurements and main results – The results confirmed that: (1) the amplitude of the early part of the plateau was depressed by low [Ca2+] and by Ca2+ antagonists, showing that ica dominates this early part; and (2) that low [Na2+] and post-extrasystolic potentiation also depressed the early component of the plateau of the action potential, which can be explained by inactivation of ica due to increased levels of intracellular Ca2+. A novel observation was that post-extrasystolic potentiation led to an increase in action potential duration (APD). An explanation is that the potentiated contraction follows from an increased amount of intracellular Ca2+ which also activates an inward current, possibly ina/ca. This assumption is strengthened by the finding that lengthening of APD after extrasystoles was abolished: (a) at low [Ca2+], ie, when force was small and there was little Ca2+ to be extruded; and (b) at low [Na+], ie, when force was large but the driving force of the Na+ gradient for extrusion of Ca2+ was small. Conclusions – The early part of the plateau is dominated by ica, whereas ina/ca is relatively more important during the later part, and tends to lengthen the action potential.
Biosynthesis of Parathyroid Hormone
Authors: Joel F. Habener, John T. Potts
Journal: New England Journal of Medicine (1978)

General Aspects of the Synthesis of Secretory ProteinsA matter of great interest has been the physiologic role of biosynthetic precursors in the pathway of the formation of parathyroid hormone and also the overall effects of biosynthetic precursors of secretory proteins generally. Many different proteins of biologic importance represented by such diverse classes as hormones, enzymes, antibodies, collagen and viral and membrane proteins are synthesized in the form of larger precursors that are subsequently modified by cleavage to smaller forms.One apparent function of a precursor sequence is evident with insulin. The C-peptide of proinsulin, the . . .
A SMALL NEEDLE FOR AVOIDING LUMBAR PUNCTURE HEADACHE
Authors: C. S. Bluemel
Journal: JAMA (1924)

The accompanying illustration shows a 3 inch No. 24 gage Luer needle used for making spinal punctures. The sliding sleeve serves as a "holder" and prevents the bending and wobbling that would otherwise occur in performing lumbar puncture with a small caliber needle. The obturator is made of No. 0 cast steel music wire. The small needle is employed to reduce the size of the puncture-hole in the dura, and thus diminish the subsequent escape of spinal fluid into the tissues. Marked decrease in the incidence of postpuncture headache results. Before the lumbar puncture is performed, the obturator wire is withdrawn a short distance into the needle. When the spinal canal has been penetrated, the obturator can be pushed forward through the point of the needle. The obturator is then withdrawn, and the spinal fluid normally flows at a rate of from 16 to 24 drops a minute with the
Serum proteins in human squamous epithelium
Authors: G. ÇORUH, D. Y. MASON
Journal: British Journal of Dermatology (1980)

SUMMARY A new immunoperoxidase staining technique of high specificity (the labelled antigen method) has been used for the detection of serum proteins in the epithelium of human skin and mucous membranes. The majority of specimens contain cells showing strong diffuse intracellular staining. These cells usually lie in the upper mid-zone of the epithelium and are often characterized by vacuolated or pyknotic nuclei. Double immunoenzymatic labelling (using alkaline phosphatase and peroxidase) showed that the different proteins are usually present in the same cells. A less frequent pattern of staining took the form of delicate strands of intercellular IgG. Samples from a wide range of skin diseases were studied, but no clear relationship between positive epithelial staining and disease states was apparent. It is suggested that serum proteins may enter epithelial cells by passive diffusion, and attention is drawn to other instances (e. g. in the central nervous system and lymphoid tissue) where similar phenomena have been observed by immunoenzymatic staining techniques.
The Bcl-2 specific BH3 mimetic ABT-199: a promising targeted therapy for t(11;14) multiple myeloma
Authors: C Touzeau, C Dousset, S Le Gouill, D Sampath, J D Leverson, A J Souers, S Maïga, M C Béné, P Moreau, C Pellat-Deceunynck, M Amiot
Journal: Leukemia (2013)

The Bcl-2 specific BH3 mimetic ABT-199: a promising targeted therapy for t(11;14) multiple myeloma
Pharmacological Facilitation of Primary Percutaneous Coronary Intervention for Acute Myocardial Infarction
Authors: Bernard J. Gersh, Gregg W. Stone, Harvey D. White, David R. Holmes
Journal: JAMA (2005)

Current options for reperfusion therapy in patients admitted to a community hospital without cardiac catheterization facilities include administration of fibrinolytic drugs followed by observation, with referral to angiography driven by symptoms and signs of ischemia; transfer to a tertiary care center for primary percutaneous coronary intervention (PCI); or a strategy of facilitated PCI in which administration of fibrinolytics and platelet glycoprotein IIb/IIIa inhibitors (alone or in combination) is followed by transfer for immediate angiography and PCI if appropriate. We systematically analyzed multiple randomized and nonrandomized trials to review the pathophysiology of reperfusion therapy in acute myocardial infarction to derive insights about the likelihood of success of a strategy of facilitated PCI compared with transfer only or fibrinolysis only. The basis for the recommendations made herein is a hypothetical curve relating the duration of symptoms before reperfusion to reduction in mortality and extent of myocardial salvage. During the first 2 to 3 hours after symptom onset, a striking benefit of reperfusion is present; within this period, time to treatment is critical. Subsequently, a mortality benefit is still present but of decreasing magnitude over time. In this situation, the priority is to open the artery, and time to treatment is less critical. Results of facilitated PCI may depend largely on timing of presentation. If presentation is late after symptom onset (ie, on the "flat" part of the curve), there will be little mortality benefit from earlier patency and patients will be subject to the bleeding risks of fibrinolytic drugs. In contrast, among patients presenting very early (60-90 minutes after symptom onset), outcomes with fibrinolytic therapy alone are excellent, and it will be difficult for any other strategy to result in a significant improvement. But in patients presenting 2 to 3 hours after onset of symptoms, a strategy of facilitated PCI may move patients from the plateau to the descending limb of the curve, with a substantial improvement in myocardial salvage and mortality. Two large ongoing trials may provide definitive answers to these issues.
Abstract 2670: CONFORMATIONAL PLASTICITY OF HUMAN THYMIDYLATE SYNTHASE
Authors: BEIBEI LUO, Sondra H. Berger
Journal: Cancer Research (2010)

Abstract Thymidylate synthase (TS), catalyzes the reaction that forms dTMP from dUMP. Previous data suggested that human thymidylate synthase (hTS) exists in two major conformations, active and inactive. Two hTS mutants were created to mimic the active and inactive forms. The mutant, designated R163K, has an arginine to lysine substitution at residue 163 and crystallizes in an active conformation in the native state. The other one, A191K, has an alanine to lysine substitution at residue 191 and is stabilized in the inactive form. To further test whether the mutants exhibit different conformations in solution, circular dichroism was used to compare solution structures and detect the effects of ligand binding. Relative to hTS, the CD spectra of both R163K and A191K showed a decreased ellipticity. Upon ligation with dUMP, A191K exhibited a further decrease in ellipticity and showed no apparent response to phosphate. In contrast, the ellipticity of R163K was increased by phosphate and dUMP produced a further increase in ellipticity. Crystal structures suggested that the catalytic thiol of R163K is more susceptible to modification by oxidation compared to hTS. Thus, we postulated that the inactive form functions to sequester the catalytic thiol from oxidation. To test the hypothesis, we conducted studies of the rate of modification of purified enzymes with the thiol-reactive agent, 5, 5′-dithiobis(2-nitrobenzoic acid) (DTNB). Relative to hTS, a slight increase in oxidation rate was observed in the active-stabilized mutant; however, the rate of catalytic inactivation of hTS was faster. In vivo, TS-deficient transfectants expressing R163K were more sensitive to oxidative stress relative to cells expressing wt hTS. The data provide preliminary evidence of a protective role of the inactive form under the oxidative stress although the basis for this effect remains unclear. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2670.
Chronic ethanol feeding increases the quantity of Gαs-protein in rat liver plasma membranes
Authors: Karen E. Iles, Laura E. Nagy
Journal: Hepatology (1995)

The liver is a primary target for both acute and chronic effects of ethanol. Because ethanol is known to alter the function of guanine nucleotide regulatory proteins (G-proteins), changes in hepatic G-proteins could contribute to the adverse effects of ethanol on liver function. Male Wistar rats were fed a liquid diet containing 36% of calories as ethanol for 4 weeks. Control rats were pair-fed or allowed free access to a diet that isocalorically substituted maltose dextrins for ethanol. Liver plasma membranes were isolated and separated into basolateral and canalicular fractions by sucrose-density gradients. Enrichment of marker enzymes (5'-nucleotidase for canalicular membranes and forskolin-stimulated adenylyl cyclase activity for basolateral membranes) was not affected by ethanol feeding. Quantity of G alpha s and G alpha i proteins in membrane fractions was determined by immunoblot. After ethanol feeding, immunoreactive G alpha s protein was increased in liver plasma membranes compared with pair-fed controls. G alpha i and G alpha s were present in both the basolateral and canalicular fractions of the plasma membrane in control and ethanol-fed rats. G alpha s quantity in the basolateral membrane was greater in ethanol-fed rats compared with controls, with no differences in G alpha s observed in canalicular membranes. The quantity of G alpha i did not change in response to ethanol feeding in any of the membrane fractions. Treatment of isolated plasma and basolateral membranes with 10 mumol/L 5'-guanylimidophosphate, a nonhydrolyzable guanosine triphosphate analogue that activates G-proteins, increased cAMP production to a greater extent in ethanol-fed rats compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Detection by ligase chain reaction of precore mutant of hepatitis B virus
Authors: S. Minamitani, S. Nishiguchi, T. Kuroki, S. Otani, T. Monna
Journal: Hepatology (1997)

The clinical diagnosis of infection with the most common precore mutant of hepatitis B virus (HBV), that with a point mutation from guanine to adenine at nucleotide 83 in the precore region, is important because the disease may progress rapidly despite interferon therapy. A practical method to detect this mutant is needed. With the ligase chain reaction (LCR), target DNA sequences can be amplified and single base mutations can be detected. We tried to detect mutant HBV by the LCR alone, but the limit of detection (10(9) copies per tube) was too high. To increase the sensitivity, we used the LCR on DNA already amplified by the polymerase chain reaction (PCR), and tested serum samples from 23 subjects with chronic HBV infection for mutant and wild-type HBV. As few as 10(2) copies per tube could be detected. The results corresponded with the results of nucleotide sequencing for 22 of the 23 patients. The ratio of clones of mutant and total viruses was estimated for each individual by PCR-coupled LCR. Seroconversion could be identified earlier in the illness by an increase in this ratio than by the decrease in HBeAg. We also tested serum samples from 11 patients with acute liver failure by PCR-coupled LCR. Mutant HBV was detected at a low ratio in all 4 patients with acute self-limited hepatitis (AH). Wild-type HBV coexisted with mutant HBV in 6 of 7 patients with fulminant hepatitis (FH), and the mean ratio of mutant to total HBV was significantly higher than that in AH. PCR-coupled LCR could be used to detect mutant HBV and to estimate the ratio of mutant to total viruses.
VENEREAL DISEASES AND NATIONAL DEFENSE
Authors: JOSEPH EARLE MOORE
Journal: JAMA (1941)

Venereal disease has been the concern of the United States Army and Navy at least since 1778. In this year Congress provided that any officer should be fined $10 and any enlisted man $4 who should be admitted to a hospital with such a disease. Aside from the purely medical measures of treatment of infected personnel, various other control steps have since been taken, including (1) a continuation of the policy of punishment for infection, differing in severity from time to time but still including (by acts of Congress, 1912 and 1914 and 107th Article of War) loss of pay and loss of time for disease acquired "as a result of misconduct,"<sup>1</sup>(2) periodic physical inspection of personnel (1899), (3) the provision of recreational facilities (1909), (4) chemical prophylaxis (1909) and later mechanical prophylaxis, (5) educational measures (1909), (6) official recognition of responsibility of unit commanders for high venereal
INAUGURAL ADDRESS AS PRESIDENT OF THE AMERICAN MEDICAL ASSOCIATION ON JUNE 12, 1928
Authors: W. S. THAYER
Journal: JAMA (1928)

'Tis with unfeigned pride and gratitude that I appear before you today, in a position of honor which I had never expected to occupy. But more than this 'tis a particular pleasure to meet in this city and in this part of the country. A New Englander by birth, a Southerner by adoption and by ties which have made the history and traditions and people of the South very dear to me, the West had always charmed me, but from afar. My real introduction to the West dates from the last meeting of this association in Minneapolis. At that time I had crossed the Mississippi but once. Since then I have reformed. In not one of the last twelve years have I missed a glimpse of Western mountain and plain, and the homesickness that I feel so often during the winter for the broad, free spaces, for the rushing rivers
Prospective, randomized controlled trial on<i>Lactobacillus rhamnosus</i>in infants with moderate to severe atopic dermatitis
Authors: R. Fölster-Holst, F. Müller, N. Schnopp, D. Abeck, I. Kreiselmaier, T. Lenz, U. Von Rüden, J. Schrezenmeir, E. Christophers, M. Weichenthal
Journal: British Journal of Dermatology (2006)

Background A reduction of symptoms of atopic dermatitis (AD) in small infants by the administration of Lactobacillus rhamnosus has been reported in a few studies. One study with older children and adolescents failed to show any effect. Objectives We conducted a prospective study to reassess the efficacy of orally administered L. rhamnosus strain GG (LGG) in infants with AD. Methods In a randomized, double-blind, placebo-controlled study, 54 infants aged 1–55 months with moderate to severe AD were randomized to daily 10 × 109 colony-forming units of LGG or to placebo during an 8-week intervention phase. Emollients, class I–II topical corticosteroids and antihistamines were permitted. Results The treatment with LGG was well tolerated. At the end of treatment there were no significant differences between the groups with respect to clinical symptoms (SCORAD, pruritus, sleep loss), the use of topical corticosteroids and antihistamines, immunological parameters, or health-related quality of life of the parents. Conclusions Our results could not confirm LGG as an effective treatment of AD in infancy.
History of the Care and Feeding of the Premature Infant
Authors: Peter C. English
Journal: JAMA (1985)

Caring for the premature infant has been on the cutting edge of pediatrics for decades. The problems confronting these infants challenge clinicians and basic scientists, pushing technologies and ethics to the limit. The survivability of ever smaller infants has provoked physicians and judges to struggle with the very definition of life itself. For the pediatric house officer, working with the premature can be the most exacting (try starting an intravenous infusion on a 750-g infant), exhausting, and frustrating part of a residency. Yet the difficulties these infants face are frequently surmountable. The challenge presented by the premature infant is a worthy historical subject, and Thomas Cone, who has previously written Two<i>Hundred Years of Feeding Infants in America</i>(1976) and<i>A History of American Pediatrics</i>(1979), is to be congratulated for tackling this difficult topic. Historians have only ventured occasionally into this area, so Cone's book is a welcomed addition.
Rapid detection of intracellular SH2D1A protein in cytotoxic lymphocytes from patients with X-linked lymphoproliferative disease and their family members
Authors: Yasuhiro Tabata, Joyce Villanueva, Susan Molleran Lee, Kejian Zhang, Hirokazu Kanegane, Toshio Miyawaki, Janos Sumegi, Alexandra H. Filipovich
Journal: Blood (2005)
The Origins of Nazi Genocide: From Euthanasia to the Final Solution
Authors: Benno Müller-Hill
Journal: JAMA (1995)

Is it possible to present novel views and materials on the origins of the German mass murder of the Jews? Henry Friedlander, a historian at the Brooklyn College of the City University of New York and a survivor of Auschwitz whose mother was murdered there, succeeds in doing so in his recent book. His view in brief is that the violent antisemitism of the Nazis in Germany fused with eugenic ideas held by the international and German medical and genetical professions. The Jews were the most important of three well-defined larger groups that were excluded from German society. Friedlander concentrates on the handicapped (the feebleminded and long-term psychiatric patients such as schizophrenics and manic-depressives) and the Gypsies. First, all rights were taken from the members of each group. Then they were imprisoned, sterilized, and murdered. In 1933 the exclusion of the handicapped and the Gypsies had already proceeded a long