tbuckley/cabot-search huggingface dataset:
T cell–mediated Fas-induced keratinocyte apoptosis plays a key pathogenetic role in eczematous dermatitis
Authors: Axel Trautmann, Mübeccel Akdis, Daniela Kleemann, Frank Altznauer, Hans-Uwe Simon, Thomas Graeve, Michaela Noll, Eva-B. Bröcker, Kurt Blaser, Cezmi A. Akdis
Journal: Journal of Clinical Investigation (2000)

Clinical and histologic similarities between various eczematous disorders point to a common efferent pathway. We demonstrate here that activated T cells infiltrating the skin in atopic dermatitis (AD) and allergic contact dermatitis (ACD) induce keratinocyte (KC) apoptosis. KCs normally express low levels of Fas receptor (FasR) that can be substantially enhanced by the presence of IFN-γ. KCs are rendered susceptible to apoptosis by IFN-γ when FasR numbers reach a threshold of approximately 40,000 per KC. Subsequently, KCs undergo apoptosis induced by anti-FasR mAb’s, soluble Fas ligand, supernatants from activated T cells, or direct contact between T cells and KCs. Apoptotic KCs show typical DNA fragmentation and membrane phosphatidylserine expression. KC apoptosis was demonstrated in situ in lesional skin affected by AD, ACD, and patch tests. Using numerous cytokines and anti-cytokine neutralizing mAb’s, we found no evidence that cytokines other than IFN-γ participate in this process. In addition, apoptosis-inducing pathways other than FasR triggering were ruled out by blocking T cell–induced KC apoptosis by caspase inhibitors and soluble Fas-Fc protein. Responses of normal human skin and cultured skin equivalents to activated T cells demonstrated that KC apoptosis caused by skin-infiltrating T cells is a key event in the pathogenesis of eczematous dermatitis.
Prune cAMP phosphodiesterase binds nm23-H1 and promotes cancer metastasis
Authors: Anna D'Angelo, Livia Garzia, Alessandra André, Pietro Carotenuto, Veruska Aglio, Ombretta Guardiola, Gianluigi Arrigoni, Antonio Cossu, Giuseppe Palmieri, L Aravind, Massimo Zollo
Journal: Cancer Cell (2004)
An Effect of Dexamethasone on Adenosine 3′,5′ -Monophosphate Content and Adenosine 3′,5′ -Monophosphate Phosphodiesterase Activity of Cultured Hepatoma Cells
Authors: Vincent Manganiello, Martha Vaughan
Journal: Journal of Clinical Investigation (1972)

The effect of dexamethasone on adenosine 3′,5′-monophosphate (cAMP) phosphodiesterase activity in cultured HTC hepatoma cells was investigated. Homogenates of these cells contain phosphodiesterase activity with two apparent Michaelis constants for cAMP (2-5 μm and 50 μm). At all substrate concentrations tested, phosphodiesterase activity was decreased 25-40% in cells incubated for 36 hr or more with 1 μm dexamethasone. Acid phosphatase activity in the same cells was not decreased. α-Methyl testosterone, 1 μm, was without effect on phosphodiesterase activity.
Most deaths related to abortion occur in the developing world
Authors: J. Ciment
Journal: BMJ (1999)

A new publication of the World Health Organization, "Abortion in the Developing World," reports that 40% of the 50 million abortions performed each year are unsafe, and 90% of these medically perilous procedures occur in developing countries. Although the 30 million abortions performed annually in developing countries represent 60% of the global total, they account for 95% of abortion-related deaths. Abortion was illegal in 94% of the developing countries included in the WHO study. Unexpectedly, the proportion of women who were using contraception when they experienced an unintended pregnancy was similar in countries with strong family planning programs and those with weak or nonexistent programs.
AMA's Role in Recognizing New Health Occupations
Authors: John J. Fauser
Journal: JAMA (1980)

For more than a decade, voices from multiple sectors have decried the proliferation and fragmentation of allied health occupations. The American Medical Association has opposed the multiplication of new categories of allied health personnel when the need for them has not been demonstrated. At the same time, however, the AMA has contended that some new types of health care personnel are indeed necessary and desirable. Each new occupation that emerges cannot be dismissed summarily under the rubric of proliferation or fragmentation, for not all proliferation is unnecessary, nor is all fragmentation divisive. Some new occupations arise in response to needs generated by new technologies, new delivery modes, or newly developed bodies of knowledge. The AMA attempted to rationalize its process of recognizing emerging health occupations in 1970 when it adopted<i>Guidelines for the Development of New Health Occupations</i>, which contain criteria for recognizing new health occupations. Such recognition is for
Fine tuning effector and regulatory T-cell dynamics: a novel tool for plaque regression?
Authors: Sabine Steffens
Journal: Cardiovascular Research (2014)

This editorial refers to ‘Regression of atherosclerosis with anti-CD3 antibody via augmenting a regulatory T-cell response in mice’ by T. Kita et al. , pp. 107–117, this issue. 

T cells are present during all stages of atherosclerosis development, and play an essential role in the initiation and progression of plaques. The majority of T lymphocytes in atherosclerotic lesions are CD4+ cells with a phenotype characteristic of the T-helper 1 (Th1) subset, producing high levels of IFN-γ.1,2 The generation of antigen-specific effector T lymphocytes during atherogenesis is likely to occur through self-antigens such as apolipoprotein (apo) B100 and oxidized low-density lipoprotein (LDL).1 Whereas most T effector cell responses have been suggested to aggravate atherosclerosis, regulatory T cells (Tregs) are increasingly recognized as potent atheroprotective players.3 Once activated, Tregs actively suppress responses of effector T cells by contact-dependent mechanisms or through the secretion of cytokines IL-10 and TGF-β. TGF-β plays a dual role in Tregs, as it regulates their differentiation and function but also is secreted as a potent effector cytokine. The functional role of Tregs in atherosclerosis models has been investigated either by direct adoptive transfer or by indirect measures such as vaccination.4,5 Another strategy is the administration of anti-CD3 antibodies (anti-CD3), either systemically or orally, which was shown to reduce atherosclerosis development at early and advanced stage.6,7 The anti-atherogenic effect of anti-CD3 involves TGF-β-dependent mechanisms via expansion and activation …
A Recessive Variant of the Romano-Ward Long-QT Syndrome?
Authors: Silvia G. Priori, Peter J. Schwartz, Carlo Napolitano, Laura Bianchi, Adrienne Dennis, Maurizio De Fusco, Arthur M. Brown, Giorgio Casari
Journal: Circulation (1998)

Background —The congenital long-QT syndrome (LQTS) is a genetically heterogeneous disease characterized by prolonged ventricular repolarization and life-threatening arrhythmias. Mutations of the KVLQT1 gene, a cardiac potassium channel, generate two allelic diseases: the Romano-Ward syndrome, inherited as a dominant trait, and the Jervell and Lange-Nielsen syndrome, inherited as an autosomal recessive trait. Methods and Results —A consanguineous family with the clinical phenotype of LQTS was screened for mutations in the KVLQT1 gene. Complementary RNAs for injection into Xenopus oocytes were prepared, and currents were recorded with the double microelectrode technique. A homozygous missense mutation, leading to an alanine-to-threonine substitution at the beginning of the pore domain of the KVLQT1 channel, was found in the proband, a 9-year-old boy with normal hearing, a prolonged QT interval, and syncopal episodes during physical exercise. The parents of the proband were heterozygous for the mutation and had a normal QT interval. The functional evaluation of the mutant channel activity showed reduction in total current, a hyperpolarizing shift in activation, and a faster activation rate consistent with a mild mutation likely to require homozygosity to manifest the phenotype. Conclusions —These findings provide the first evidence for a recessive form of the Romano-Ward long-QT syndrome and indicate that homozygous mutations on KVLQT1 do not invariably produce the Jervell and Lange-Nielsen syndrome. The implications of this observation prompt a reconsideration of the penetrance of different mutations responsible for LQTS and suggest that mild mutations in LQTS genes may be present among the general population and may predispose to drug-induced ventricular arrhythmias.
Skeletal muscle membrane lipid composition is related to adiposity and insulin action.
Authors: D A Pan, S Lillioja, M R Milner, A D Kriketos, L A Baur, C Bogardus, L H Storlien
Journal: Journal of Clinical Investigation (1995)

The cellular basis of insulin resistance is still unknown; however, relationships have been demonstrated between insulin action in muscle and the fatty acid profile of the major membrane structural lipid (phospholipid). The present study aimed to further investigate the hypothesis that insulin action and adiposity are associated with changes in the structural lipid composition of the cell. In 52 adult male Pima Indians, insulin action (euglycemic clamp), percentage body fat (pFAT; underwater weighing), and muscle phospholipid fatty acid composition (percutaneous biopsy of vastus lateralis) were determined. Insulin action (high-dose clamp; MZ) correlated with composite measures of membrane unsaturation (% C20-22 polyunsaturated fatty acids [r= 0.463, P < 0.001], unsaturation index [r= -0.369, P < 0.01]), a number of individual fatty acids and with delta5 desaturase activity (r= 0.451, P < 0.001). pFAT (range 14-53%) correlated with a number of individual fatty acids and delta5 desaturase activity (r= -0.610, P < 0.0001). Indices of elongase activity (r= -0.467, P < 0.001), and delta9 desaturase activity (r= 0.332, P < 0.05) were also related to pFAT but not insulin action. The results demonstrate that delta5 desaturase activity is independently related to both insulin resistance and obesity. While determining the mechanisms underlying this relationship is important for future investigations, strategies aimed at restoring "normal" enzyme activities, and membrane unsaturation, may have therapeutic importance in the "syndromes of insulin resistance."
Use of Thiazolidinediones and Risk of Heart Failure in People With Type 2 Diabetes: A Retrospective Cohort Study: Response to Karter et al.
Authors: Thomas E. Delea, John S. Edelsberg, May Hagiwara, Gerry Oster, Lawrence S. Phillips
Journal: Diabetes Care (2004)

We thank Karter et al. (1) for their comments regarding our study (2). We agree that its principal weakness is the possibility of residual confounding, and we acknowledge this limitation in our article. We also agree that comparison of patients initiating thiazolidinediones (TZDs) with all those receiving other oral antidiabetic agents (new starters plus those on maintenance therapy) may have biased our findings against TZDs. On the other hand, the alternative of comparing patients initiating therapy with TZDs with those initiating other oral antidiabetic agents could have imparted a potentially more serious bias to the study because (as Karter et al. note) the former may be more likely to be initiated later in the course of the disease than the latter. Lacking data on the duration of diabetes, we chose an approach that we hoped would …
Chip Fractures of Carpal Cuneiform
Authors: T. J. Fairbank
Journal: BMJ (1942)

Case Reports Case 1.-A woman aged 21 was admitted to hospital because of menorrhagia.ShIe had had the trouble ever since her periods started at the age of 12.At 15 there appeared on the left leg an ulcer which was very indolent and did not heal for more than two years.During this time it gradually increased in size until it measured about tO by 5 cm.When she was 17 a similar ulcer appeared on the right leg; but cleared in a shorter time.Neither had broken down since.On the lower third of both legs there were large thin paper-like scars.There was no surrounding discoloration, and the scars were not tender.As the patient had only 19,000 platelets per c.mm., splenectomy was advised, and a spleen weighing 284 g. was removed by Mr. Elliot-Smith.The patient made an excellent recovery.She was completely relieved of all symptoms, and seven months after operation her platelets numbered 338,000 per c.mm. Case 2.-A man aged 26 was admitted to hospital because of excessive bleeding after incision of a boil.All his life he had
A NOVEL UNGATED CARDIAC MAGNETIC RESONANCE PERFUSION PROTOCOL FOR THE DETECTION OF SIGNIFICANT SINGLE AND MULTIVESSEL CORONARY DISEASE IN PATIENTS WITH ATRIAL FIBRILLATION
Authors: Lowell Chang, Promporn Suksaranjit, Gangadhar Malasana, Allen Rassa, Ganeshsharma Adluru, Krishna Velagapudi, Devarvrat Likhite, Alexis Harrison, Brent Wilson, Christopher McGann, Nassir Marrouche, Edward DiBella
Journal: Journal of the American College of Cardiology (2014)
Early-life risk factors and incidence of rhinitis: Results from the European Community Respiratory Health Study—an international population-based cohort study
Authors: Melanie Claire Matheson, Shyamali Chandrika Dharmage, Michael John Abramson, Eugene Haydn Walters, Jordi Sunyer, Roberto de Marco, Benedicte Leynaert, Joachim Heinrich, Deborah Jarvis, Dan Norbäck, Chantal Raherison, Matthias Wjst, Cecilie Svanes
Journal: Journal of Allergy and Clinical Immunology (2011)
PSYCHONEUROSES INCIDENTAL TO PRE-FLIGHT AND PRIMARY FLIGHT PILOT TRAINING
Authors: WALTER O. KLINGMAN
Journal: American Journal of Psychiatry (1943)

An attempt has been made to describe the major psychological reactions observed in aviation cadets in the pre-flight and primary flying phases of pilot training. The successful completion of the pre-flight phase carries with it the necessary adaptability for strictly disciplined group living plus the successful repression and suppression of the fears incidental to the approaching military flying. The successful completion of the primary flying phase calls for more specific ability to suppress not only the fears of military flying but also the somatic accompaniments of flying.
A common variant in the patatin-like phospholipase 3 gene (PNPLA3) is associated with fatty liver disease in obese children and adolescents
Authors: Nicola Santoro, Romy Kursawe, Ebe D'Adamo, Daniel J. Dykas, Clarence K. Zhang, Allen E. Bale, Anna M. Calí, Deepak Narayan, Melissa M. Shaw, Bridget Pierpont, Mary Savoye, Derek Lartaud, Samuel Eldrich, Samuel W. Cushman, Hongyu Zhao, Gerald I. Shulman, Sonia Caprio
Journal: Hepatology (2010)

The genetic factors associated with susceptibility to nonalcoholic fatty liver disease (NAFLD) in pediatric obesity remain largely unknown. Recently, a nonsynonymous single-nucleotide polymorphism (rs738409), in the patatin-like phospholipase 3 gene ( PNPLA3 ) has been associated with hepatic steatosis in adults. In a multiethnic group of 85 obese youths, we genotyped the PNLPA3 single-nucleotide polymorphism, measured hepatic fat content by magnetic resonance imaging and insulin sensitivity by the insulin clamp. Because PNPLA3 might affect adipogenesis/lipogenesis, we explored the putative association with the distribution of adipose cell size and the expression of some adipogenic/lipogenic genes in a subset of subjects who underwent a subcutaneous fat biopsy. Steatosis was present in 41% of Caucasians, 23% of African Americans, and 66% of Hispanics. The frequency of PNPLA3 (rs738409) G allele was 0.324 in Caucasians, 0.183 in African Americans, and 0.483 in Hispanics. The prevalence of the G allele was higher in subjects showing hepatic steatosis. Surprisingly, subjects carrying the G allele showed comparable hepatic glucose production rates, peripheral glucose disposal rate, and glycerol turnover as the CC homozygotes. Carriers of the G allele showed smaller adipocytes than those with CC genotype ( P = 0.005). Although the expression of PNPLA3, PNPLA2, PPARγ2 (peroxisome proliferator-activated receptor gamma 2), SREBP1c (sterol regulatory element binding protein 1c), and ACACA (acetyl coenzyme A carboxylase) was not different between genotypes, carriers of the G allele showed lower leptin ( LEP )( P = 0.03) and sirtuin 1 ( SIRT1 ) expression ( P = 0.04). Conclusion: A common variant of the PNPLA3 gene confers susceptibility to hepatic steatosis in obese youths without increasing the level of hepatic and peripheral insulin resistance. The rs738409 PNPLA3 G allele is associated with morphological changes in adipocyte cell size. (Hepatology 2010.)
Successful use of entecavir for a severe case of reactivation of hepatitis B virus following polychemotherapy containing rituximab
Authors: Mayra J. Sanchez, Maria Buti, Maria Homs, Andres Palacios, Francisco Rodriguez-Frias, Rafael Esteban
Journal: Journal of Hepatology (2009)

Hepatitis B virus (HBV) reactivation following treatment with rituximab has been reported in patients with either HBsAg-positive, or HBsAg-negative and anti-HBc positive infection. Patients with severe reactivation often have a fatal outcome despite treatment with lamivudine. The use of entecavir has not been reported in patients with severe HBV reactivation.We present a case of a HBsAg-negative patient diagnosed with chronic lymphocytic leukemia who received a chemotherapeutic regimen that included rituximab, who subsequently presented with severe HBV reactivation with ascites, jaundice and coagulopathy and was treated with entecavir. A review of the literature and underlying HBV associated mutations are discussed.Entecavir produced a rapid and sustained suppression of HBV that was associated with rapid clinical improvement without any side effects.Entecavir is an efficacious and safe treatment for severe HBV reactivation.
Racial Disparities in the Quality of Care for Enrollees in Medicare Managed Care
Authors: Eric C. Schneider
Journal: JAMA (2002)

ContextSubstantial racial disparities in the use of some health services exist; however, much less is known about racial disparities in the quality of care.ObjectiveTo assess racial disparities in the quality of care for enrollees in Medicare managed care health plans.Design and SettingObservational study, using the 1998 Health Plan Employer Data and Information Set (HEDIS), which summarized performance in calendar year 1997 for 4 measures of quality of care (breast cancer screening, eye examinations for patients with diabetes, β-blocker use after myocardial infarction, and follow-up after hospitalization for mental illness).ParticipantsA total of 305 574 (7.7%) beneficiaries who were enrolled in Medicare managed care health plans had data for at least 1 of the 4 HEDIS measures and were aged 65 years or older.Main Outcome MeasuresRates of breast cancer screening, eye examinations for patients with diabetes, β-blocker use after myocardial infarction, and follow-up after hospitalization for mental illness.ResultsBlacks were less likely than whites to receive breast cancer screening (62.9% vs 70.9%; P&lt;.001), eye examinations for patients with diabetes (43.6% vs 50.4%; P = .02), β-blocker medication after myocardial infarction (64.1% vs 73.8%; P&lt;.005), and follow-up after hospitalization for mental illness (33.2 vs 54.0%; P&lt;.001). After adjustment for potential confounding factors, racial disparities were still statistically significant for eye examinations for patients with diabetes, β-blocker use after myocardial infarction, and follow-up after hospitalization for mental illness.ConclusionAmong Medicare beneficiaries enrolled in managed care health plans, blacks received poorer quality of care than whites.
The Los Angeles Riots of 2014: How to Avert Them
Authors: George A. Gellert
Journal: JAMA (1992)

To the Editor.  —In the aftermath of the Los Angeles riots of 1992, there is a discomforting sense that American society has embarked on an inevitable, repetitive cycle. Although shocked, can communities across the nation truly be surprised by the events that transpired or by their magnitude? A ritualized laying of blame, promise of federal aid to cities, and the commission investigations are all unfolding predictably. Of concern is that fatigued, well-worn rationales continue to guide the policy debate and response. These can be summarized as advocacy of education to engender economic opportunity and escape from poverty. Absent from this discussion is any focus on physical or mental health. As such, this formula will not prevent repetition of riots in Los Angeles and other American cities. While the social, political, and economic roots of poverty and community dysfunction must certainly be addressed, they do not exist in a vacuum. As
Suppression of Hematopoietic-Progenitor-Cell Proliferation by Ethanol and Acetaldehyde
Authors: Richard C. Meagher, Fritz Sieber, Jerry L. Spivak
Journal: New England Journal of Medicine (1982)

The effects of alcohol on bone marrow are not well understood. We measured the influence of ethanol and its metabolite, acetaldehyde, on the in vitro proliferation of hematopoietic progenitor cells from mice and human beings. Colony formation by both early and late erythroid progenitor cells was suppressed by concentrations of ethanol (0.05 to 0.2 per cent) that are easily achieved in vivo. The corresponding suppressing concentration of acetaldehyde was 0.001 per cent. In contrast, suppression of granulocyte/macrophage progenitor cells required 3.0 per cent ethanol or 0.03 per cent acetaldehyde. Spleen colony formation by pluripotent stem cells was resistant to concentrations of ethanol and acetaldehyde that suppressed in vitro colony formation of committed myeloid and erythroid progenitor cells by 50 per cent. The suppression of both myeloid and erythroid colony formation was partially reversed by supplementing the cultures with folinic acid or pyridoxine. These data provide an explanation for the preferential suppression of erythropoiesis observed clinically in ethanol abuse. They also suggest that acetaldehyde has a role in ethanol-mediated bone-marrow suppression. (N Engl J Med. 1982; 307:845–9.)
Commentary: Markov models of medical prognosis
Authors: A. Briggs, M. Sculpher
Journal: BMJ (1997)

Objective:To monitor the natural course of otitis media with effusion.Design: Prospective, longitudinal assessment of the state of the middle ear by otoscopy and tympanometry at monthly intervals from birth to 3 years.Setting: Domiciliary visits to family homes.Subjects: 95 full term infants born between August 1991 and November 1993.Main outcome measures: Observed and simulated data (Monte Carlo) for the duration of single episodes of otitis media with effusion.Results: 17 of the children had unilateral or bilateral otitis media with effusion for more than half of their first three years of life.Thirty three of the 95 children had tympanograms suggestive of otitis media with effusion at more than a third of observations; the remaining 62 had such tympanograms at less than a third of observations.The data of each group were described by a first order Markov model, yielding a mean duration of unilateral effusion episodes of 5-6 weeks in both groups; the mean duration of bilateral effusion was 6 and 10 weeks in the low and high incidence groups, respectively.However, the main difference between the groups was the time spent between episodes of effusion: effusion free periods were, on average, three times longer in the children who experienced less otitis media with effusion. Conclusion:Children who are susceptible to otitis media with effusion tend to have more separate episodes of effusion rather than an increased overall duration of episodes.Such children are primarily distinguished by the likelihood with which they acquire the disease than by their ability to recover from it.
Mast cells and neutrophils proteolytically activate chemokine precursor CTAP-III and are subject to counterregulation by PF-4 through inhibition of chymase and cathepsin G
Authors: Florian Schiemann, Tobias Alexander Grimm, Josef Hoch, Roland Gross, Buko Lindner, Frank Petersen, Silvia Bulfone-Paus, Ernst Brandt
Journal: Blood (2005)