tbuckley/cabot-search huggingface dataset:
Regulatory dendritic cell expression of <scp>MHC</scp>II and <scp>IL</scp>‐10 are jointly requisite for induction of tolerance in a murine model of <scp>OVA</scp>‐asthma
Authors: H. Huang, W. Dawicki, M. Lu, A. Nayyar, X. Zhang, J. R. Gordon
Journal: Allergy (2013)

Abstract Background Allergen‐presenting dendritic cells differentiated with IL ‐10 ( DC 10) reverse the asthma phenotype in mice by converting their Th2 cells to regulatory T cells ( T regs). DC 10 express elevated levels of IL ‐10, but substantially reduced levels of MHCII and costimulatory molecules, so the relationships between these factors with each other and tolerogenicity have not been clearly elucidated. Methods We assessed the roles of these inputs in DC 10 reversal of OVA ‐associated asthma‐like disease by treating affected mice with OVA ‐pulsed DC 10 generated from wild‐type or IL ‐10‐sufficient MHCII −/− or CD 80/ CD 86 −/− mice, or with MHCII ‐intact IL ‐10‐silenced DC 10. Results IL ‐10 silencing did not discernibly affect the cells' immunobiology (e.g., costimulatory molecules, chemokines), but it eliminated IL ‐10 secretion and the cell's abilities to induce tolerance, as determined by assessments of airway hyper‐responsiveness, eosinophilia, and T h2 responses to recall OVA challenge. MHCII −/− DC 10 expressed normal levels of IL ‐10, but, nevertheless, were unable to induce allergen tolerance in asthma phenotype mice, while tolerance induced by CD 80/ CD 86 −/− DC 10 was attenuated but not eliminated. We also assessed the induction of multiple T reg cell markers (e.g., ICOS , PD ‐1, GITR ) on pulmonary CD 25 + Foxp3 + cells in the treated mice. Wild‐type DC 10 treatments upregulated expression of each marker, while neither IL ‐10‐silenced nor MHCII −/− DC 10 did so, and the CD 80/86 −/− DC 10 induced an intermediate T reg cell activation phenotype. Conclusion Both IL ‐10 and MCHII expression by DC 10 are requisite, but not sufficient for tolerance induction, suggesting that DC 10 and Th2 effector T cells must be brought together in a cognate fashion in order for their IL ‐10 to induce tolerance.
RE: Courage Beyond Science
Authors: Richard W. Biek
Journal: JAMA (1977)

<h3>To the Editor.—</h3> Dr Dimond's commencement address (236:2085,1976) is eloquent and stirring. He clearly and pointedly raises many important issues, and concludes with the advice, "Physician: know yourself." Such an inspiring goal helps us focus our energies in order to gain self-knowledge. And yet, we are in the midst of constantly changing life experiences, values, and priorities; and there is no way to know how we will act in the future—even though in the past we may have taken many courageous stands. We are humanly incapable of knowing absolute truth, and unless traditional standards are constantly reinterpreted and modified as life moves forward, they may become irrelevant and even stifling. Answering the questions posed by Dr Dimond is a never-ending struggle with conflicting concepts and impulses. Pat solutions tend to be self-righteous and inhumane. Caring about and knowing oneself and others is a painful and rewarding process in which both
Comment on ‘No major role for glutathione S-transferase gene polymorphisms in sensitization to para-phenylenediamine and other xenobiotics: a study of association and a meta-analysis’: reply from authors
Authors: L.M. Pot, B.Z. Alizadeh, D. Ahrenberg, P.-J. Coenraads, H. Snieder, B. Blömeke
Journal: British Journal of Dermatology (2011)
A 47-Year-Old Man With Asymptomatic Hepatitis C Infection, 1 Year Later
Authors: Thomas L. Delbanco
Journal: JAMA (1996)

In December 1995, at the Medicine Grand Rounds, Dr Michael Sorrell discussed Mr E, an impoverished man with a long history of substance abuse found to have asymptomatic hepatitis C infection during screening while he was in prison. Laboratory evaluation showed normal liver function tests, and the patient continued to feel well when first seen 3 years later by a general internist, Dr A. Dr A found no hepatomegaly, and liver function tests remained normal. Serologic testing for both hepatitis C and hepatitis B antibodies was positive. The patient's wife, who had tested negative for hepatitis C, was concerned about sexual transmission of hepatitis, and she urged the patient and his physician to consider further diagnostic and possible therapeutic strategies for his infection. Dr Sorrell discussed the natural history, infectiousness, and management of hepatitis C, pointing out the frequently insidious course of progression to life-threatening disease. Nevertheless, given the lack
Cutting Into Cholesterol-Reply
Authors: John M. Eisenberg
Journal: JAMA (1988)

<h3>In Reply.—</h3> Dr Goldstein raises the difficult issue of whether the lack of overall mortality reduction in primary prevention trials implies that there are no benefits, in terms of life expectancy, from reducing cholesterol levels. He correctly points out that the only study to show a definite mortality benefit was a secondary prevention trial using niacin. Those studies that have examined the cost-effectiveness of cholesterol reduction<sup>1</sup>or the expected gain in life-years<sup>2</sup>have used the relationship between cholesterol level reduction and primary cardiovascular end points (myocardial infarction and coronary-related death) observed in the Coronary Primary Prevention Trial (CPPT) as quantitative validation of the cholesterol-coronary heart disease risk identified in the Framingham Heart Study, and have calculated years of life gained from the Framingham data set. We restricted our analysis to coronary heart disease-related morbidity and mortality because we could see no reasonable causal link between cholestyramine and accidental
HIV-Associated Coronary Arteritis in a Patient with Fatal Myocardial Infarction
Authors: Giuseppe Barbaro, Giorgio Barbarini, Adriano M. Pellicelli
Journal: New England Journal of Medicine (2001)

To the Editor: Coronary disease has been reported previously in patients infected with the human immunodeficiency virus (HIV) who are receiving protease inhibitors1 or who are also infected with cy...
739 CIRCULATING AND HEPATIC ENDOCANNABINOIDS AND ENDOCANNABINOID-RELATED MOLECULES IN PATIENTS WITH LIVER CIRRHOSIS
Authors: P. Caraceni, A. Viola, M. Domenicali, F. Piscitelli, S. Petrosino, F. Giannone, A. Berzigotti, M. Zoli, M. Cescon, G. Grazi, V. Di Marzo, M. Bernardi
Journal: Journal of Hepatology (2009)
Asymmetric dimethylarginine is strongly associated with cognitive dysfunction and brain MR spectroscopic abnormalities in cirrhosis
Authors: Jasmohan S. Bajaj, Vishwadeep Ahluwalia, James B. Wade, Arun J. Sanyal, Melanie B. White, Nicole A. Noble, Pamela Monteith, Michael Fuchs, Richard K. Sterling, Velimir Luketic, Iliana Bouneva, Richard T. Stravitz, Puneet Puri, Kenneth A. Kraft, HoChong Gilles, Douglas M. Heuman
Journal: Journal of Hepatology (2012)
Polyarthritis Associated With Clindamycin-lnduced Colitis
Authors: Douglas E. Rollins
Journal: JAMA (1975)

<h3>To the Editor.—</h3> In their article, Cohen et al (223:1379, 1973) described pseudomembranous colitis following therapy with clindamycin hydrochloride. Despite the association of arthritis with inflammatory intestinal disease, there are no reports in the literature of arthritis occurring with antibiotic-induced colitis. We would like to report a case of pseudomembranous colitis with acute migratory polyarthritis following therapy with clindamycin. <h3>Report of a Case.—</h3> A 55-year-old man with no previous history of intestinal or arthritic disease had nonspecific sialadenitis and was treated for 12 days with clindamycin hydrochloride, 150 mg orally four times a day. During the course of therapy, he had two to three loose stools per day, increasing to eight to ten watery, mucoid, nonbloody stools daily. This persisted for four weeks. Twenty-seven days after stopping clindamycin therapy, when his diarrhea was most severe, he had an acute migratory polyarthritis involving the shoulders, elbows, knees, ankles, and the metacarpophalangeal
Gastric Bypass Surgery in Severely Obese Type 1 Diabetic Patients
Authors: Leszek Czupryniak, Janusz Strzelczyk, Katarzyna Cypryk, Maciej Pawlowski, Dariusz Szymanski, Andrzej Lewinski, Jerzy Loba
Journal: Diabetes Care (2004)

Obesity is common in type 2 diabetes but is rarely seen in autoimmune type 1 diabetes (1). However, as shown in the Diabetes Control and Complications Trial cohort (2,3), a subset of type 1 diabetic patients are overweight, and it has been suggested that intensive insulin therapy may unmask the central obesity or metabolic syndrome in susceptible individuals.

Gastric bypass is considered a gold standard procedure in the surgical treatment of severe obesity, with >50% of excess weight loss occurring within 2 years after the surgery. The weight reduction is maintained over the following years in a vast majority of patients (4). Numerous reports have been published on the beneficial effects of obesity surgery on glucose control and metabolic disorders in impaired glucose tolerant and type 2 diabetic subjects, with an impressive 70–90% of diabetic patients remaining euglycemic without diabetes medications several years after the surgery (5,6). This significant impact of gastric bypass surgery on glucose control is thought to not only result from significant weight loss but also from the exclusion of hormonally active foregut (7, …
Attributable risk, population attributable risk, and population attributable fraction of death associated with hypertension in a biracial population.
Authors: D C Deubner, H A Tyroler, J C Cassel, C G Hames, C Becker
Journal: Circulation (1975)

In 1961, blood pressure was measured in the 40-69-year-old segment of the population of Evans County, Georgia. Mortality was monitored for up to ten years. The relationship found between hypertension and mortality is characterized in this report by four parameters: attributable risk, prevalence, population attributable risk, and population attributable fraction. Attributable risk of death, a measure of the over-all impact of hypertension on those in each race-sex group with hypertension, is high in white males, black males, and black females, and is lowest in white females. Population attributable risk, a measure of the impact of hypertension on each entire race-sex group, is highest in black males and females due to the high prevalence of hypertension in blacks. It is somewhat lower in white males and lowest in white females. The fraction of all deaths attributable to hypertension (population attributable fraction) is highest in black females and lower in the other three groups. The population attributable fraction (ranging from 0.26 to 0.54 for systolic hypertension) is of such magnitude that if the 50% reduction in mortality achieved in the Veteran Administration Cooperative Study could be repeated in the general population, life expectancy after 40 years of age could be substantially increased.
Response to Exercise in Congenital Complete Atrioventricular Block
Authors: DANAE IKKOS, JOHN S. HANSON
Journal: Circulation (1960)

The electrocardiographic and hemodynamic responses to graded exercise in 11 patients with congenital complete atrioventricular block are described. Ventricular rate increases during exercise were unrelated to the resting rate, atrial rate, or heart size. Changes in the ratio of atrial: ventricular rates were observed in all cases during physical work. Physical working capacity was normal or only slightly reduced in all instances. This is accomplished through maintenance of normal minute volumes, which in turn reflects an interplay of several factors: acceleration of ventricular rate, increased heart volume and stroke volume, and a normal or supernormal oxygen-transporting capacity of the blood as reflected in increased amount of total hemoglobin.
Letter: Stereotaxic neurosurgery for cerebral palsy.
Authors: E Hitchcock
Journal: BMJ (1975)

risk in patients receiving long-term pheno- barbitone or phenytoin therapy.Exposure to enzyme-inducing agents such as drugs, industrial and agricultural chemicals, pesticides, food additives, etc, is a hazard of living in the more highly developed countries.It is tempting to speculate that the differences in serum cholesterol between such populations and those of less affluent countries, which have never been fully ex- plained by differences in dietary intakes of animal fat,89 may in part be due to differ- ences in their degree of enzyme induction.
A Social Connection Model for International Clinical Research
Authors: Agomoni Ganguli Mitra
Journal: The American Journal of Bioethics (2013)

Click to increase image sizeClick to decrease image size Acknowledgments This open peer commentary refers to the target article “Evaluating the Capacity of Theories of Justice to Serve as a Justice Framework for International Clinical Research” by Bridget Pratt, Deborah Zion, and Bebe Loff (2012), which appeared in The American Journal of Bioethics 12(11): 30–41.
Hemodynamic Effects of Direct Biventricular Compression Studied in Isovolumic and Ejecting Isolated Canine Hearts
Authors: John H. Artrip, Jie Wang, Andrew R. Leventhal, Joshua E. Tsitlik, Howard R. Levin, Daniel Burkhoff
Journal: Circulation (1999)

Background —Biventricular direct cardiac compression (DCC) can potentially support the failing heart without the complications associated with a blood/device interface. The effect of uniform DCC on left and right ventricular performance was evaluated in 7 isolated canine heart preparations. Methods and Results —A computer-controlled afterload system either constrained the isolated heart to contract isovolumically or simulated hemodynamic properties of physiological ejection. Biventricular DCC was provided by a chamber surrounding the heart that allowed adjustment of the compression pressure, onset time, and duration. Through a series of ventricular preloads, the effect of DCC on the end-systolic pressure-volume relationship (ESPVR) was evaluated under isovolumic and ejecting conditions. Under both conditions, DCC shifted the ESPVR of the left and right ventricles upward by an amount approximately equal to the compression pressure. The augmentation of end-systolic pressure for each initial preload tested, however, was less under ejecting conditions, because reductions in end-systolic and end-diastolic volumes occurred with ejection. Nevertheless, the net effect was to increase stroke volume. Measurement of MV̇ o 2 demonstrated that at a given ventricular volume, MV̇ o 2 did not change with DCC; however, peak ventricular pressure increased substantially, so that the effective pressure-volume area increased. Conclusions —Biventricular DCC can augment end-systolic pressure with no added costs of MV̇ o 2 . Under ejecting conditions, this augmentation of ventricular contracting ability manifests as increases in stroke volume. Thus, DCC represents a feasible alternative form of ventricular assist, and devices that support the heart in this manner should be further explored.
Urinary Kallikrein Excretion in Hypertensive Man
Authors: HARRY S. MARGOLIUS, DAVID HORWITZ, JOHN J. PISANO, HARRY R. KEISER
Journal: Circulation Research (1974)

Urinary kallikrein excretion was measured by a radiochemical esterolytic assay in patients with essential hypertension or primary aldosteronism. Patients with essential hypertension excreted significantly less ( P &lt; 0.001) kallikrein than did normal subjects when they were allowed an ad libitum sodium intake or given 259 mEq sodium/day. When sodium intake was changed from ad libitum to 9 mEq/day, kallikrein excretion increased in the majority of patients with essential hypertension, but it remained significantly less ( P &lt; 0.001) than that in normal subjects; however, aldosterone excretion was similar in both groups. Fludrocortisone, 0.5 mg/day for 10 days, increased kallikrein excretion in three patients with essential hypertension. In patients with primary aldosteronism, mean kallikrein excretion was sevenfold higher ( P &lt; 0.001) than that in patients with essential hypertension; kallikrein excretion remained unchanged when dietary sodium was altered, but it was decreased by treatment with spironolactone. Mean kallikrein excretion in patients with primary aldosteronism was also significantly higher ( P &lt; 0.001) than that in a normotensive control population. The results show that kallikrein excretion reflects the effective level of circulating sodium-retaining steroid in patients with primary aldosteronism but suggest that it is relatively unresponsive to endogenous sodium-retaining steroid in patients with essential hypertension. The data raise the possibility that the kallikrein-kinin system is of pathogenetic significance in human hypertensive disease.
Regulation of Cytokine-Induced Nitric Oxide Synthesis by Asymmetric Dimethylarginine
Authors: Seiji Ueda, Seiya Kato, Hidehiro Matsuoka, Masumi Kimoto, Seiya Okuda, Minoru Morimatsu, Tsutomu Imaizumi
Journal: Circulation Research (2003)

In response to vascular insults, inflammatory cytokines stimulate vascular smooth muscle cells (SMCs) to express an inducible isoform of nitric oxide synthase (iNOS). Asymmetric dimethylarginine (ADMA), an endogenous NO synthase inhibitor, is metabolized by dimethylarginine dimethylaminohydrolase (DDAH). To determine whether the ADMA-DDAH system regulates cytokine-induced NO production, cultured rat SMCs were exposed to interleukin-1beta (IL-1beta). IL-1beta (1 to 100 U/mL) dose-dependently stimulated not only iNOS but also DDAH expression and enzyme activity, accompanied by an increase in NO metabolite and by a decrease in ADMA content in culture media. A DDAH inhibitor (4124W, 5 mmol/L) augmented ADMA production (P<0.01) and decreased NO synthesis (P<0.01) in IL-1beta-stimulated SMCs. On the other hand, an adenovirus-mediated overexpression of DDAH reduced ADMA and enhanced NO production. Exogenous administration of NO donors (SNAP and SIN-1) dose-dependently increased NO metabolite in the culture media but had no effect on ADMA. Our results indicate two mechanisms of IL-1beta-induced NO synthesis: the direct stimulation of the expression of iNOS and the indirect stimulation of iNOS activity by upregulating DDAH and reducing ADMA. The ADMA-DDAH system may be another regulatory mechanism of inflammation-mediated NO production for human vascular diseases.
Oxidant Stress Impairs In Vivo Reendothelialization Capacity of Endothelial Progenitor Cells From Patients With Type 2 Diabetes Mellitus
Authors: Sajoscha A. Sorrentino, Ferdinand H. Bahlmann, Christian Besler, Maja Müller, Svenja Schulz, Nina Kirchhoff, Carola Doerries, Tibor Horváth, Anne Limbourg, Florian Limbourg, Danilo Fliser, Hermann Haller, Helmut Drexler, Ulf Landmesser
Journal: Circulation (2007)

Background— Endothelial progenitor cells (EPCs) are thought to contribute to endothelial recovery after arterial injury. We therefore compared in vivo reendothelialization capacity of EPCs derived from patients with diabetes mellitus and healthy subjects. Moreover, we examined the effect of treatment with the peroxisome proliferator-activated receptor-γ agonist rosiglitazone on oxidant stress, nitric oxide (NO) bioavailability, and the in vivo reendothelialization capacity of EPCs from diabetic individuals. Methods and Results— In vivo reendothelialization capacity of EPCs from diabetic patients (n=30) and healthy subjects (n=10) was examined in a nude mouse carotid injury model. Superoxide and NO production of EPCs was determined by electron spin resonance spectroscopy. Thirty patients with diabetes mellitus were randomized to 2 weeks of rosiglitazone (4 mg BID PO) or placebo treatment. In vivo reendothelialization capacity of EPCs derived from diabetic subjects was severely reduced compared with EPCs from healthy subjects (reendothelialized area: 8±3% versus 37±10%; P &lt;0.001). EPCs from diabetic individuals had a substantially increased superoxide production and impaired NO bioavailability. Small-interfering RNA silencing of NAD(P)H oxidase subunit p47 phox reduced superoxide production and restored NO bioavailability and in vivo reendothelialization capacity of EPCs from diabetic patients. Importantly, rosiglitazone therapy normalized NAD(P)H oxidase activity, restored NO bioavailability, and improved in vivo reendothelialization capacity of EPCs from diabetic patients (reendothelialized area: placebo versus rosiglitazone, 8±1% versus 38±5%; P &lt;0.001). Conclusions— In vivo reendothelialization capacity of EPCs derived from individuals with diabetes mellitus is severely impaired at least partially as a result of increased NAD(P)H oxidase–dependent superoxide production and subsequently reduced NO bioavailability. Rosiglitazone therapy reduces NAD(P)H oxidase activity and improves reendothelialization capacity of EPCs from diabetic individuals, representing a potential novel mechanism whereby peroxisome proliferator-activated receptor-γ agonism promotes vascular repair.
Mast cell CD30 ligand is upregulated in cutaneous inflammation and mediates degranulation-independent chemokine secretion
Authors: Marie Fischer, Ilkka T. Harvima, Ricardo F.S. Carvalho, Christine Möller, Anita Naukkarinen, Gunilla Enblad, Gunnar Nilsson
Journal: Journal of Clinical Investigation (2006)

Mast cells are involved in many disorders where the triggering mechanism that leads to degranulation and/or cytokine secretion has not been defined. Several chronic inflammatory diseases are associated with increased mast cell numbers and upregulation of the TNF receptor family member CD30, but the role of elevated CD30 expression is poorly understood. Here we report what we believe to be a novel way to activate mast cells with CD30 that leads to degranulation-independent secretion of chemokines. CD30 induced a de novo synthesis and secretion of the chemokines IL-8, macrophage inflammatory protein-1alpha (MIP-1alpha), and MIP-1beta, a process involving the MAPK/ERK pathway. Mast cells were found to be the predominant CD30 ligand-positive (CD30L-positive) cell in the chronic inflammatory skin diseases psoriasis and atopic dermatitis, and both CD30 and CD30L expression were upregulated in lesional skin in these conditions. Furthermore, the number of IL-8-positive mast cells was elevated both in psoriatic and atopic dermatitis lesional skin as well as in ex vivo CD30-treated healthy skin organ cultures. In summary, characterization of CD30 activation of mast cells has uncovered an IgE-independent pathway that is of importance in understanding the entirety of the role of mast cells in diseases associated with mast cells and CD30 expression. These diseases include Hodgkin lymphoma, atopic dermatitis, and psoriasis.
Reducing Mortality in Patients with Extensive Myocardial Infarction
Authors: James T. Willerson, O.H. Frazier
Journal: New England Journal of Medicine (1991)

In this issue of the Journal, Goldberg et al. have estimated the incidence of cardiogenic shock complicating acute myocardial infarction.1 Their study includes more than 4000 patients cared for over a 14-year period at hospitals in the Worcester, Massachusetts, metropolitan area. The data indicate that the incidence of cardiogenic shock complicating acute myocardial infarction remained relatively constant during this period, averaging 7.5 percent. In-hospital mortality rates did not improve between 1975 and 1988; during this time, 74 percent to 82 percent of the patients died.These results may not be surprising. Patients with cardiogenic shock generally have 40 percent . . .