tbuckley/cabot-search huggingface dataset:
CD30-mediated signaling promotes the development of human T helper type 2-like T cells.
Authors: G Del Prete, M De Carli, M M D'Elios, K C Daniel, F Almerigogna, M Alderson, C A Smith, E Thomas, S Romagnani
Journal: The Journal of Experimental Medicine (1995)

We have recently shown that CD30, a member of the tumor necrosis factor/nerve growth factor receptor superfamily, is preferentially expressed by human T cell clones producing T helper (Th) type 2 cytokines. We report here that costimulation with an agonistic anti-CD30 monoclonal antibody enhanced antigen (Ag)-induced proliferation and cytokine secretion by established human Th2 and Th0 clones. Moreover, costimulation of peripheral blood mononuclear cells with the same anti-CD30 monoclonal antibody resulted in the preferential development of Ag-specific T cell lines and clones showing a Th2-like profile of cytokine secretion. In contrast, early blockade in bulk culture of CD30 ligand-CD30 interaction shifted the development of Ag-specific T cells towards the opposite (Th1-like) phenotype. Taken together, these data suggest that CD30 triggering of activated Th cells by CD30 ligand-expressing Ag-presenting cells may represent an important costimulatory signaling for the development of Th2-type responses.
Molecular mediators of hepatic steatosis and liver injury
Authors: Jeffrey D. Browning, Jay D. Horton
Journal: Journal of Clinical Investigation (2004)

Obesity and its associated comorbidities are among the most prevalent and challenging conditions confronting the medical profession in the 21st century. A major metabolic consequence of obesity is insulin resistance, which is strongly associated with the deposition of triglycerides in the liver. Hepatic steatosis can either be a benign, noninflammatory condition that appears to have no adverse sequelae or can be associated with steatohepatitis: a condition that can result in end-stage liver disease, accounting for up to 14% of liver transplants in the US. Here we highlight recent advances in our understanding of the molecular events contributing to hepatic steatosis and nonalcoholic steatohepatitis.
Suicidal Behavior and Severe Neuropsychiatric Disorders Following Glucocorticoid Therapy in Primary Care
Authors: Laurence Fardet, Irene Petersen, Irwin Nazareth
Journal: American Journal of Psychiatry (2012)

An epidemiological study of British general practice patients who received oral glucocorticoids showed that patients who received these drugs were seven times as likely to attempt suicide as were patients with the same illness who did not receive steroids. The increase was most prominent in younger people. Mania and delirium were also significantly more common, particularly in older men. Neuropsychiatric effects were more common in patients receiving higher doses and those with previous mental disorders.
Effects of the novel antiarrhythmic agent azimilide on experimental atrial fibrillation and atrial electrophysiologic properties
Authors: S Nattel
Journal: Cardiovascular Research (1998)

Objectives: This study was designed to evaluate how the atrial electrophysiological and antiarrhythmic effects of azimilide compare with those of the specific rapid delayed rectifier (IKr) blocker dofetilide. Background: Azimilide, a new class III drug, was initially believed to be a highly selective blocker of the slow delayed rectifier (IKs), but recent studies suggest that azimilide potently blocks IKr. Thus, it has been suggested that azimilide's in vivo effects may simply be due to IKr blockade. Methods: Dose regimens producing stable effects over time were developed, and two dose levels of azimilide (10 and then 20 mg/kg) or dofetilide (0.08 and then 0.16 mg/kg) were administered to morphine/chloralose-anesthetized dogs during sustained vagal atrial fibrillation (AF). Epicardial mapping was used to measure conduction velocity and AF cycle length. Results: Azimilide terminated AF in 13/14 dogs (93%), while dofetilide terminated AF in 6/12 (50%, P<0.05). While dofetilide had strong reverse use-dependent effects on atrial ERP (e.g. at lower doses, dofetilide increased ERP by 51±3% at a basic cycle length, BCL, of 400 ms and by 17±3% at a BCL of 200 ms), azimilide's effects on ERP were rate-independent (ERP increased at lower dose by 38±6%, BCL 400 ms; 35±10%, BCL 200 ms). Neither drug affected conduction. Conclusions: Azimilide is effective against experimental AF, and increases ERP with a frequency dependence different from the IKr blocker dofetilide, suggesting that azimilide's actions on atrial tissue cannot be attributed exclusively to IKr block, and that effects on other currents (such as IKs) are likely to be important.
364 Involvement of poly(ADP-ribose) polymerase-1 (PARP-1) in the developement and treatment of hepatocellular carcinoma
Authors: R. Quiles, A. Ruiz Extremera, J. Salmerón, T. Caballero, P. Muñoz-Ruedal, J. Casadol, F.J. Oliver
Journal: Journal of Hepatology (2006)
RELATIONSHIP OF INCIDENT ATRIAL FIBRILLATION TO RENAL FUNCTION IN HYPERTENSIVE PATIENTS WITH ELECTROCARDIOGRAPHIC LEFT VENTRICULAR HYPERTROPHY: THE LIFE STUDY
Authors: Peter M. Okin, Darcy Hille, Kristian Wachtell, Sverre Kjeldsen, Bjorn Dahlof, Richard Devereux
Journal: Journal of the American College of Cardiology (2014)
Abstract 4843: Neutrophil elastase enhances adaptive immunity via increase of peptide presentation and downregulation of T cell inhibitory molecules
Authors: Akhil Chawla, Anne V. Philips, Na Qiao, Pariya Sukhumalchandra, Celine Kerros, Gheath Alatrash, Jeffrey J. Molldrem, Elizabeth A. Mittendorf
Journal: Cancer Research (2014)

Abstract Introduction: Neutrophil elastase (NE) is an inflammatory mediator that is taken up by breast cancer cells. We have previously shown that NE uptake increases susceptibility to lysis by cytotoxic T lymphocytes (CTL) targeting the tumor antigens PR1 and cyclin E. We investigated whether NE uptake alters adaptive immunity by affecting MHC class I antigen presentation and T cell inhibitory molecules. Methods: MDA-MB-231 breast cancer cells were maintained in standard media ± NE. Healthy donor HLA-A2+ peripheral blood mononuclear cells were used to generate antigen specific CTL by pulsing dendritic cells with E75, a HER2-derived epitope we are currently investigating as a vaccine in clinical trials. Calcein-AM cytotoxicity assays evaluated E75-specific lysis. Flow cytometry was used to show NE uptake, HLA-A2, pan-HLA class I (HLA-ABC) and PD-L1 surface expression. Western blot analysis was used to show total MHC class I heavy chain, B2M, LMP2, TAP1, calnexin and tapasin expression. Relative PD-L1 mRNA levels were determined using qPCR. Results: NE uptake enhanced tumor cell lysis by E75-specific CTL at all effector to target (E:T) ratios (lysis for 20 to 1 E:T ratio was 50% ± 7 for NE treated vs 28% ± 7 for untreated, p &amp;lt; 0.05), and led to an increase in HLA-A2 and HLA-ABC surface expression (p &amp;lt; 0.05; Table). However, NE uptake did not change total expression of MHC class I or components of the MHC class I pathway. Additionally, NE uptake led to a decrease in PD-L1 surface expression and transcript levels (p &amp;lt; 0.05; Table). Conclusion: NE increases tumor antigen presentation as well as MHC class I on the cell surface. However, NE uptake does not change total MHC class I expression or expression of MHC class I antigen processing components, suggesting that NE increases peptide availability as a mechanism of increased MHC class I antigen presentation. NE also leads to the downregulation of PD-L1. Together, our data indicate that NE uptake enhances adaptive immune responses. HLA-A2 Surface Expression (MFI)HLA-ABC Surface Expression (MFI)PD-L1 Surface Expression (MFI)PD-L1 mRNA Expression (RQ)NE Treated (Mean ± SD)7341 ± 8671317 ± 1201723 ± 550.274 ± 0.02Untreated (Mean ± SD)5144 ± 272802 ± 1336966 ± 4511 Citation Format: Akhil Chawla, Anne V. Philips, Na Qiao, Pariya Sukhumalchandra, Celine Kerros, Gheath Alatrash, Jeffrey J. Molldrem, Elizabeth A. Mittendorf. Neutrophil elastase enhances adaptive immunity via increase of peptide presentation and downregulation of T cell inhibitory molecules. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4843. doi:10.1158/1538-7445.AM2014-4843
Peutz-Jeghers Syndrome Associated With Functioning Ovarian Tumor
Authors: C.D. Christian, Thomas G. McLoughlin, Edward R. Cathcart, M. Michael Eisenberg
Journal: JAMA (1964)

PEUTZ,<sup>1</sup>in 1921, reported the association of skin pigmentation and small bowel polyps in several members of a family. Jeghers<sup>2</sup>added two such patients to the literature in 1944 and, in 1949 along with McKusick and Katz,<sup>3</sup>he established the syndrome as an entity which appears to be inherited as a mendelian dominant. Since that time additional cases have brought the reported number to somewhat over 100.<sup>4</sup> An additional patient, a 41/2-year-old girl with the rare syndrome of mucocutaneous pigmentation and gastrointestinal polyposis, is presented below because of the associated presence of a granulosatheca cell tumor of the ovary with resultant precocious puberty. The interest aroused by the coincidence of these two rare disorders has been further stimulated by the isolated reports<sup>5,6</sup>of two other cases of Peutz-Jeghers syndrome associated granulosa cell tumors. <h3>Report of a Case</h3> A 41/2-year-old girl was admitted for
283 INDEPENDENT PREDICTORS OF DISCORDANCE BETWEEN TRANSIENT ELASTOGRAPHY (TE) AND LIVER BIOPSY (LB)
Authors: M. Fraquelli, C. Rigamonti, D. Conte, G. Casazza, M.F. Donate, M.G. Rumi, P. Lampertico, G. Ronchi, M. Colombo
Journal: Journal of Hepatology (2008)
Inhibition of Constitutive Signaling of Kaposi's Sarcoma–associated Herpesvirus G Protein–Coupled Receptor by Protein Kinases in Mammalian Cells in Culture
Authors: Elizabeth Geras-Raaka, Leandros Arvanitakis, Carlos Bais, Ethel Cesarman, Enrique A. Mesri, Marvin C. Gershengorn
Journal: The Journal of Experimental Medicine (1998)

Kaposi's sarcoma–associated herpesvirus (KSHV)/human herpesvirus 8, which is consistently present in tissues of patients with Kaposi's sarcoma and primary effusion lymphomas, contains a gene that encodes a G protein–coupled receptor (KSHV-GPCR). We recently showed that KSHV-GPCR exhibits constitutive signaling via activation of phosphoinositide-specific phospholipase C and stimulates cell proliferation and transformation. In this study, we determined whether normal cellular mechanisms could inhibit constitutive signaling by KSHV-GPCR and thereby KSHV-GPCR–stimulated proliferation. We show that coexpression of GPCR-specific kinases (GRKs) and activation of protein kinase C inhibit constitutive signaling by KSHV-GPCR in COS-1 monkey kidney cells and in mouse NIH 3T3 cells. Moreover, GRK-5 but not GRK-2 inhibits KSHV-GPCR–stimulated proliferation of rodent fibroblasts. These data provide evidence that cell regulatory pathways of receptor desensitization may be therapeutic targets in human diseases involving constitutively active receptors.
Primary cutaneous large-cell lymphoma: analysis of 49 patients included in the LNH87 prospective trial of polychemotherapy for high-grade lymphomas
Authors: P Brice, D Cazals, N Mounier, O Verola, AM Neidhart-Berard, L Remenieras, E Deconinck, C Doyen, J Hamelsand, T Molina, I Moulonguet, C Gisselbrecht
Journal: Leukemia (1998)
Acute Heroin Overdose
Authors: Karl A. Sporer
Journal: Annals of Internal Medicine (1999)

Acute heroin overdose is a common daily experience in the urban and suburban United States and accounts for many preventable deaths. Heroin acts as a pro-drug that allows rapid and complete central nervous system absorption; this accounts for the drug's euphoric and toxic effects. The heroin overdose syndrome (sensitivity for diagnosing heroin overdose, 92%; specificity, 76%) consists of abnormal mental status, substantially decreased respiration, and miotic pupils. The response of naloxone does not improve the sensitivity of this diagnosis. Most overdoses occur at home in the company of others and are more common in the setting of other drugs. Heroin-related deaths are strongly associated with use of alcohol or other drugs. Patients with clinically significant respiratory compromise need treatment, which includes airway management and intravenous or subcutaneous naloxone. Hospital observation for several hours is necessary for recurrence of hypoventilation or other complications. About 3% to 7% of treated patients require hospital admission for pneumonia, noncardiogenic pulmonary edema, or other complications. Methadone maintenance is an effective preventive measure, and others strategies should be studied.
Class I chitinases with hevein-like domain, but not class II enzymes, are relevant chestnut and avocado allergens
Authors: Araceli Diaz-Perales, Carmen Collada, Carlos Blanco, Rosa Sánchez-Monge, Teresa Carrillo, Cipriano Aragoncillo, Gabriel Salcedo
Journal: Journal of Allergy and Clinical Immunology (1998)
Actigraphy for children with eczema
Authors: C. Wootton, K. Thomas
Journal: British Journal of Dermatology (2013)

Funding sources: No external funding. Conflicts of interest: None declared. Madam, Dr Kawada raises several concerns regarding our recent paper.1 Our study used data generated through the randomized controlled Softened Water Eczema Trial, and we aimed to specifically evaluate how useful actigraphy is as an outcome measure in clinical trials that are evaluating response to treatment. Therefore, actigraphy data would have had to correlate with other, already validated outcome measures as well as demonstrate responsiveness to changes in disease activity to prove useful in our stated context. Unfortunately, actigraphy was not found to correlate with other outcome measures or to reflect changes in disease activity. The first question is regarding the use of the Patient Oriented Eczema Measure (POEM), which has been validated in patients aged between 1 and 58 years of age. Dr Kawada suggests that it would have been preferable to have a validation study for this measure specifically in young children. While this may be an ideal, Schmitt et al.2 demonstrated that POEM was one of only three eczema severity scales that have been sufficiently well validated to recommend their use in clinical trials.
<i>Fire-Swept, Algoma</i>
Authors: Thomas B. Cole
Journal: JAMA (2014)

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
Exercise, Fitness, and Mortality
Authors: Randall B. Lauffer
Journal: JAMA (1990)

<h3>To the Editor.—</h3> The study by Blair et al<sup>1</sup>clearly demonstrates the beneficial effect of fitness, if not exercise itself, in decreasing the mortality rate from both heart disease and cancer. A number of distinct mechanisms, none of which are totally satisfactory, have been proposed to account for this effect on these two very different diseases. In the case of coronary artery disease, the beneficial effect of exercise is thought to arise from improvements in lipid profile, ventricular function, or other cardiocirculatory parameters. For colon cancer, on the other hand, exercise is thought to increase bowel motility and thus reduce exposure to potential carcinogens. I propose the hypothesis that the preventive effects of exercise are due in part to lower body iron levels that result from exercise-induced blood loss or other alterations in iron metabolism. The evidence for the role of iron in both coronary artery disease and
Rural Health Care
Authors: David J. Ottensmeyer, Howard L. Smith
Journal: New England Journal of Medicine (1982)

Abstract Many rural areas of the United States are considered medically underserved. At the core of this underservice is a lack of physicians. Physicians are not attracted to rural areas for a variety of personal and professional reasons. We explore the role of established group practices (EGPs) in dealing with these barriers, by using a model of small associated group practices (AGPs) created in rural communities in association with a larger EGP located elsewhere. We also describe the use of this model by the Lovelace Medical Foundation in New Mexico in creating three rural group practices and planning a fourth. (N Engl J Med. 1982; 306:74–8.)
ACRIFLAVINE PASTE AS A DRESSING FOR INFECTED WOUNDS
Authors: C. J. Bond
Journal: BMJ (1917)

_BIA _OO-u y There were three tracheotomies (includingone emer- gency laryngotomy) and elevenm haeboiorhWhaes necdssf- tating ligature of the external, and three-of the common carotid.These.tliree latter are a1l mQk,d' ap'palrently not sufferiing any discomforts as a consequence of tlisi operation.
Role of local prostaglandin synthesis in the modulation of proliferative activity of rat colonic epithelium.
Authors: P A Craven, R Saito, F R DeRubertis
Journal: Journal of Clinical Investigation (1983)

The role of local prostaglandin (PG) synthesis in the modulation of the proliferative activity of colonic epithelium was examined in rat colon. Experimental rats were given either indomethacin (5 mg/kg s.c. every 8 h for three doses) or aspirin (0.5 g/100 g diet for 3 d). In rats treated with indomethacin or aspirin, the incorporation of [3H]thymidine (dThd) into DNA in vivo was increased approximately twofold over control in mucosal scrapings from distal colon, and approximately threefold over control in the proliferating pool of epithelial cells isolated from distal colon. [3H]dThd incorporation into DNA was also examined ex vivo immediately after distal colonic resection. It was approximately twofold higher in mucosa of colonic segments (1-h incubation) from rats treated with indomethacin or aspirin in vivo, compared with corresponding values of segments from control rats. Immunoreactive (i) prostaglandin E (PGE), the dominant PG product of colon segment incubates by high-performance liquid chromatography analysis of [14C]arachidonate metabolites, was markedly (95%) reduced in the media of 1-h colon incubates from indomethacin- or aspirin-treated rats, compared with control rats. Moreover, the cyclic (c)AMP content of mucosa of segments from indomethacin- or aspirin-treated rats was significantly lower than that of control rats. Prolonged incubation (4-24 h) of colonic segments from indomethacin-treated rats, in the absence of indomethacin in vitro, led to an eventual return of [3H]dThd incorporation into DNA, iPGE, and mucosal cAMP to control values. Conversely, inclusion of indomethacin (0.25 mM) in the incubations (6 h) of colonic segments from indomethacin-treated rats resulted in persistent suppression of iPGE and mucosal cAMP, as well as persistent enhancement of [3H]dThd incorporation into mucosal DNA. However, incubation of colonic segments from control rats (no in vivo drug exposure) with indomethacin or aspirin in vitro for periods up to 24 h failed to alter DNA synthesis, despite marked reduction in media iPGE and lower mucosal cAMP. The latter observations suggested that additional in vivo factors initiated the enhancement of DNA synthesis in indomethacin- or aspirin-treated rats. Exogenous PGE2, D2, I2, or F2 alpha, each of which increased the endogenous mucosal cAMP content of incubated colonic segments from control, indomethacin- or aspirin-treated rats, all suppressed [3H]dThd incorporation into mucosal DNA in vitro. Dibutyryl cAMP, but not dibutyryl cGMP, had an analogous suppressive effect on in vitro [3H]dThd incorporation into DNA. Thus, the present observations are consistent with an inhibitory action of endogenous colonic PG synthesis on the proliferative activity of colonic epithelium. This action may be mediated through cAMP.
Esophageal lichen planus: a series of eight cases including a patient with esophageal verrucous carcinoma. A case series
Authors: A. Chryssostalis, M. Gaudric, B. Terris, R. Coriat, F. Prat, S. Chaussade
Journal: Endoscopy (2008)

Esophageal lichen planus is a rare condition. Its risk of malignant transformation is unknown. We report a series of eight patients with esophageal lichen planus referred to our unit between 1990 and 2005. Clinical, endoscopic, radiological and histological data of these patients were retrospectively reviewed. Seven patients were women. All patients had oral lichen planus. Endoscopic lesions were located in the upper third of the esophagus in seven patients and in the mid third in two patients. Five patients had esophageal stricture. Seven patients had peeling, friable esophageal mucosa. Histological examination of esophageal biopsies found characteristic features of lichen planus in two patients and nonspecific changes in five patients. All patients received corticosteroids. Patients with stricture underwent esophageal dilation. Esophageal perforation after dilation occurred in one patient. Corticosteroids improved dysphagia in all patients; steroid dependence occurred in two patients with stricture. One patient had an esophageal verrucous carcinoma, which was treated with radiotherapy and chemotherapy. Upper endoscopy should be performed in patients with mucosal lichen planus presenting with dysphagia to assess esophageal involvement. Esophageal strictures are frequent and require dilation. Corticosteroids are the first-line treatment, but steroid dependence may occur. Cancer can arise on esophageal lichen planus and justifies endoscopic follow-up.