tbuckley/cabot-search huggingface dataset:
Prevalence of inflammatory bowel disease in British 26 year olds: national longitudinal birth cohort
Authors: S M Montgomery, D L Morris, N P Thompson, J Subhani, R E Pounder, A J Wakefield
Journal: BMJ (1998)

tended to be higher (P = 0.07).In the placebo group, the difference in heart rate at high altitude was positively correlated with maximum headache scores (r = 0.8, P < 0.01) and inversely related to saturation values 3 hours after arrival at high altitude (r = -0.8,P < 0.01; figure).
Retinoic Acid Can Directly Promote TGF-β-Mediated Foxp3+ Treg Cell Conversion of Naive T Cells
Authors: Daniel Mucida, Karina Pino-Lagos, Gisen Kim, Elizabeth Nowak, Micah J. Benson, Mitchell Kronenberg, Randolph J. Noelle, Hilde Cheroutre
Journal: Immunity (2009)
Eosinophils in Asthma — Closing the Loop or Opening the Door?
Authors: Sally E. Wenzel
Journal: New England Journal of Medicine (2009)

Although the origin of the concept that eosinophils are critical to asthma pathobiology remains controversial, there is consensus that Paul Ehrlich first identified a bilobed nucleated cell as an "eosin"-ophil in 1879 on the basis of the cell's granular uptake of his newly discovered dye. These cells were soon found in airway tissues and "catarrh" (sputum) of patients with asthma. Over the years, eosinophils were identified as a prominent cell type in asthma, yet their role as either an "effector" or "innocent bystander" was not confirmed until the publication of articles by Nair et al.1 and Haldar et al.2 in . . .
Filaggrin haploinsufficiency is highly penetrant and is associated with increased severity of eczema: further delineation of the skin phenotype in a prospective epidemiological study of 792 school children
Authors: S.J. Brown, C.L. Relton, H. Liao, Y. Zhao, A. Sandilands, W.H.I. McLean, H.J. Cordell, N.J. Reynolds
Journal: British Journal of Dermatology (2009)

Background Null mutations within the filaggrin gene (FLG) cause ichthyosis vulgaris and are associated with atopic eczema. However, the dermatological features of filaggrin haploinsufficiency have not been clearly defined. Objectives This study investigated the genotype–phenotype association between detailed skin phenotype and FLG genotype data in a population-based cohort of children. Methods Children (n = 792) aged 7–9 years were examined by a dermatologist. Features of ichthyosis vulgaris, atopic eczema and xerosis were recorded and eczema severity graded using the Three Item Severity score. Each child was genotyped for the six most prevalent FLG null mutations (R501X, 2282del4, R2447X, S3247X, 3702delG, 3673delC). Fisher's exact test was used to compare genotype frequencies in phenotype groups; logistic regression analysis was used to estimate odds ratios and penetrance of the FLG null genotype and a permutation test performed to investigate eczema severity in different genotype groups. Results Ten children in this cohort had ichthyosis vulgaris, of whom five had mild–moderate eczema. The penetrance of FLG null mutations with respect to flexural eczema was 55·6% in individuals with two mutations, 16·3% in individuals with one mutation and 14·2% in wild-type individuals. Summating skin features known to be associated with FLG null mutations (ichthyosis, keratosis pilaris, palmar hyperlinearity and flexural eczema) showed a penetrance of 100% in children with two FLG mutations, 87·8% in children with one FLG mutation and 46·5% in wild-type individuals (P < 0·0001, Fisher exact test). FLG null mutations were associated with more severe eczema (P = 0·0042) but the mean difference was only 1–2 points in severity score. Three distinct patterns of palmar hyperlinearity were observed and these are reported for the first time. Conclusions Filaggrin haploinsufficiency appears to be highly penetrant when all relevant skin features are included in the analysis. FLG null mutations are associated with more severe eczema, but the effect size is small in a population setting.
Injuries from propane gas grills
Authors: R. A. Schieber
Journal: JAMA (1996)

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
Increased Endoplasmic Reticulum Stress in Atherosclerotic Plaques Associated With Acute Coronary Syndrome
Authors: Masafumi Myoishi, Hiroyuki Hao, Tetsuo Minamino, Kouki Watanabe, Kensaku Nishihira, Kinta Hatakeyama, Yujiro Asada, Ken-ichiro Okada, Hatsue Ishibashi-Ueda, Giulio Gabbiani, Marie-Luce Bochaton-Piallat, Naoki Mochizuki, Masafumi Kitakaze
Journal: Circulation (2007)

The endoplasmic reticulum (ER) responds to various stresses by upregulation of ER chaperones, but prolonged ER stress eventually causes apoptosis. Although apoptosis is considered to be essential for the progression and rupture of atherosclerotic plaques, the influence of ER stress and apoptosis on rupture of unstable coronary plaques remains unclear.Coronary artery segments were obtained at autopsy from 71 patients, and atherectomy specimens were obtained from 40 patients. Smooth muscle cells and macrophages in the fibrous caps of thin-cap atheroma and ruptured plaques, but not in the fibrous caps of thick-cap atheroma and fibrous plaques, showed a marked increase of ER chaperone expression and apoptotic cells. ER chaperones also showed higher expression in atherectomy specimens from patients with unstable angina pectoris than in specimens from those with stable angina. Expression of 7-ketocholesterol was increased in the fibrous caps of thin-cap atheroma compared with thick-cap atheroma. Treatment of cultured coronary artery smooth muscle cells or THP-1 cells with 7-ketocholesterol induced upregulation of ER chaperones and apoptosis, whereas these changes were prevented by antioxidants. We also investigated possible signaling pathways for ER-initiated apoptosis and found that the CHOP (a transcription factor induced by ER stress)-dependent pathway was activated in unstable plaques. In addition, knockdown of CHOP expression by small interfering RNA decreased ER stress-dependent death of cultured coronary artery smooth muscle cells and THP-1 cells.Increased ER stress occurs in unstable plaques. Our findings suggest that ER stress-induced apoptosis of smooth muscle cells and macrophages may contribute to plaque vulnerability.
Angiotensin-converting enzyme: II. Pulmonary endothelial cells in culture.
Authors: U S Ryan, J W Ryan
Journal: Environmental Health Perspectives (1980)

Direct studies of the function of a given cell type often require that the cell type be obtained in pure culture. A number of different specific metabolic activities have been attributed to pulmonary endothelial cells, yet with few exceptions the conclusions were based on indirect evidence. Thus, to improve our ability to examine directly for specific metabolic activities, we began a program to obtain pulmonary endothelial cells in culture. Two methods have been developed: (1) cells can be obtained from pulmonary artery and vein of large animals (cow, pig), and (2) cells can be obtained from the microvasculature of small animals (rat, guinea pig, and rabbit). The latter technique can also be used to obtain cells from a lobe of lung from large animals and may be adaptable for use with human tissue. In the first technique, pulmonary arteries, free of blood, are filled with collagenase (0.25%, 500 units) in Puck's saline for 25 min. The collagenase mixture containing cells is removed and centrifuged. The pellet is resuspended and seeded into culture flasks. In the second method, lungs are perfused (artery to vein) with Krebs-Henseleit solution until the effluent is blood-free. Collagenase (0.25%, 500 units) is introduced, and the lungs are then perfused in the opposite direction (vein to artery) until the flow stops spontaneously (ca. 15 min). The detached cells are collected and seeded as before. The endothelial cells attach as small clumps (10-50 cells). Those flasks which contain more than 95% endothelial cells (by phase microscopy) are retained for culture and the lines are purified usng differential adherence procedures. The cells grow as monolayers with a cobblestone appearance. They contain Weibel-Palade bodies. They possess converting enzyme activity and are reactive with antibodies to converting enzyme, Factor VIII and alpha 2-macroglobulin. The cells synthesize prostaglandins and related substances. In addition, they possess ADPase and synthesize angiotensin-converting enzyme.
Clinical Trials Have Gone Global: Is This a Good Thing?
Authors: Trudie Lang, Sisira Siribaddana
Journal: PLoS Medicine (2012)

SS has been funded by the Wellcome Trust UK and had several travel grants from Servier (before 1999), Novo Nordisk (before 1999), and Elly Lilly (before 1999). SS is also ethics review committee chairman of the Faculty of Medicine and Allied Sciences Rajarata University of Sri Lanka. TAL has declared that no competing interests exist.



No specific funding was received for writing this article.



Provenance: Commissioned; externally peer reviewed.
Lysosome destruction and lipoperoxide formation due to active oxygen generated from haematoporphyrin and UV irradiation
Authors: WAKIO TORINUKI, TAKASHI MIURA, MAKOTO SEIJI
Journal: British Journal of Dermatology (1980)

The lysosomal enzymes, acid-phosphatase and beta-glucuronidase, were released from rat liver lysosome when exposed to 400 nm irradiation in the presence of haematoporphyrin, and the release was prevented by adding vitamin E, diazabicyclo-octane, bovine serum albumin, superoxide dismutase or D-mannitol to the reaction mixture. Monochromatic irradiation with wavelengths from 380 to 410 nm caused no significant differences in the release of lysosomal enzymes, but 420 nm irradiation caused three-fifths of that of 400 nm irradiation. The malondialdehyde level in rat liver homogenate increased after 400 nm irradiation in the presence of haematoporphyrin. Reduction of nitroblue-tetrazolium was not observed when haematoporphyrin was excited by 400 nm; it was considered that superoxide anion radical (O2--) was not primarily generated. The following mechanism was assumed: that porphyrin which had been excited by 400 nm, converted ground-state molecular oxygen (3O2) to excited singlet oxygen (1O2), which formed lipid peroxides in lysosomal membrane resulting in destruction of the membrane; skin changes would occur from these released lysosomal enzymes.
An Angiogenesis Inhibitor E7820 Shows Broad-Spectrum Tumor Growth Inhibition in a Xenograft Model
Authors: Taro Semba, Yasuhiro Funahashi, Naoto Ono, Yuji Yamamoto, Naoko Hata Sugi, Makoto Asada, Kentaro Yoshimatsu, Toshiaki Wakabayashi
Journal: Clinical Cancer Research (2004)

We reported previously that an angiogenesis inhibitor, E7820, inhibits in vitro tube formation of human umbilical vein endothelial cell through the suppression of integrin alpha2 expression. Here we describe the antiangiogenic and antitumor effects of E7820 in mice and discuss the feasibility of using platelet integrin alpha2 expression on platelets as a biological marker of the efficacy of E7820. Oral administration of E7820 significantly inhibited basic fibroblast growth factor-induced angiogenesis in Matrigel implants and human colon WiDr tumor-induced angiogenesis in a dorsal air sac model. Twice-daily treatment with E7820 clearly inhibited the s.c. tumor growth of seven tumor cell lines derived from human colon, breast, pancreas, and kidney, and completely suppressed the growth of human pancreatic KP-1 and human colon LoVo cell lines. Moreover, E7820 significantly inhibited the growth of KP-1 and human colon tumor Colo320DM cells orthotopically implanted in the pancreas and cecum, respectively. The efficacy of E7820 was comparable in the s.c. and orthotopic transplantation models. Immunohistochemical analyses using anti-CD31 antibody showed that E7820 significantly reduced microvessel density in orthotopically implanted KP-1 tumor. E7820 reduced integrin alpha2 expression on a megakaryocytic cell line, Dami cells, induced by phorbol 12-myristate 13-acetate treatment. It also decreased the expression level of integrin alpha2 on platelets withdrawn from mice bearing s.c. KP-1 tumor at a dosage close to that affording antitumor activity. These data demonstrate that E7820 showed a broad-spectrum antitumor effect in mice through inhibition of angiogenesis and indicate that the decrease of integrin alpha2 on platelets might serve as a biological marker for the antitumor efficacy of E7820.
Hepatitis C reactivation in patients with chronic infection with genotypes 1b and 2c: a retrospective cohort study of 206 untreated patients
Authors: M G Rumi
Journal: Gut (2005)

<b>Background:</b> We previously described hepatitis reactivation in two carriers of the hepatitis C virus (HCV) genotype 2c. <b>Aim:</b> To assess the relationship between HCV genotypes and risk of hepatitis reactivation, we studied the course of aminotransferases in patients infected with the two relevant genotypes in Italy. <b>Patients:</b> A cohort of 100 patients with genotype 2c chronic hepatitis and 106 with genotype 1b were subjected to surveillance. <b>Methods:</b> Hepatitis reactivation was defined as an alanine aminotransferase (ALT) value ⩾400 IU/l or a maximum/minimum ALT ratio value of ⩾8. <b>Results:</b> Over a period of 71 (24–144) months, one or more flares of ALT (201–2200 IU/l, 6–90 months' duration) occurred in 31 patients with genotype 2c and in eight patients with genotype 1b (rates of flares: 55.6 per 1000 person years for genotype 2c <i>v</i> 15.0 for genotype 1b; p = 0.001). On repeat biopsy, hepatic fibrosis increased by more than 2 points in 10/16 patients examined either during or after an ALT flare compared with 7/36 flare free patients (63% <i>v</i> 19%; p = 0.003). Hepatitis flares were significantly associated with genotype 2c (odds ratio 6.48 (95% confidence interval 2.57–16.35)) but not with sex, age, modality or duration of infection, baseline ALT values or histological severity of hepatitis, hepatitis other than HCV, or reinfection. <b>Conclusions:</b> Genotype 2c carriers are at high risk of hepatitis reactivation, suggesting that virus genetic heterogeneity is important in the natural history of HCV, questioning the linearity of hepatic fibrosis progression during hepatitis C.
Margaret Joan Fingland (nee Croall)
Authors: I. W Fingland
Journal: BMJ (2002)

Former family doctor Greenlaw, Berwickshire (b 1927; q Glasgow 1951; DRCOG), died peacefully at home on 25 December 2001.

She shared in a traditional husband and wife partnership practice in Greenlaw for many years and was able to initiate family planning services in Berwickshire. Despite progressive disability caused by multiple sclerosis, she continued to consult from a wheelchair. Following retirement, she remained an active participant on medical committees and organisations for disabled people. She leaves a husband, Ian; two children; and five grandchildren.
Multiple Mechanisms of Na <sup>+</sup> Channel– Linked Long-QT Syndrome
Authors: Robert Dumaine, Qing Wang, Mark T. Keating, Hali A. Hartmann, Peter J. Schwartz, Arthur M. Brown, Glenn E. Kirsch
Journal: Circulation Research (1996)

Inheritable long-QT syndrome (LQTS) is a disease in which delayed ventricular repolarization leads to cardiac arrhythmias and the possibility of sudden death. In the chromosome 3-linked disease, one mutation of the cardiac Na+ channel gene results in a deletion of residues 1505 to 1507 (Delta KPQ), and two mutation result in substitutions (N1325S and R1644H). We compared all three mutant-channel phenotypes by heterologous expression in Xenopus oocytes. Each produced a late phase of inactivation-resistant, mexiletine- and tetrodotoxin-sensitive whole-cell currents, but the underlying mechanisms were different at the single-channel level. N1325S and R1644H showed dispersed reopenings after the initial transient, whereas Delta KPQ showed both dispersed reopenings and long-lasting bursts. Thus, two distinct biophysical defects underlie the in vitro phenotype of persistent current in Na+ channel-linked LQTS, and the additive effects of both are responsible for making the Delta KPQ phenotype the most severe.
Abstract 4755: The role of a pair of cysteine residues in the redox properties of human ribonucleotide reductase small subunits hp53R2 and hRRM2
Authors: Bingsen Zhou, Leila Su, Shuya Hu, Yun Yen
Journal: Cancer Research (2012)

Abstract Ribonucleotide reductase (RNR) is a cell cycle protein regulating intracellular redox state, which is a critical mediator and metabolic modulator of cellular functions such as cell signaling, gene expression, proliferation, and apoptosis. Human RNR has two small subunits hp53R2 and hRRM2, which by themselves play important roles in regulating cellular redox state. Our previous studies have shown that hRRM2 and hp53R2 have different redox properties, where hp53R2 is an antioxidant defending oxidative stress while hRRM2 tends to be an oxidant. Many proteins consist of cysteine residues which have a sulfhydryl group with a labile proton, making it an ideal “receptor” through the reversibility of the thiol/disulfide redox couple. In this work we have found human RNR small subunits possess a conserved CXXXC motif, C270XXXC274 in hRRM2 and C232XXXC236 in hp53R2, close to Tyr162-hRRM2/Tyr124-hp53R2. Our mutagenesis study indicated this motif is linked with the redox properties of hp53R2 and hRRM2. The cysteines were mutated to serine and alanine respectively and the redox state of the mutants were monitored by the fluorescence assays of carboxy-H2DCFDA oxidation. Electron paramagnetic resonance spectroscopy (EPR) and enzyme activity assays were also carried out for the radical stability and enzyme activity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4755. doi:1538-7445.AM2012-4755
Loss of Collectrin, an Angiotensin-Converting Enzyme 2 Homolog, Uncouples Endothelial Nitric Oxide Synthase and Causes Hypertension and Vascular Dysfunction
Authors: Sylvia Cechova, Qing Zeng, Marie Billaud, Stephanie Mutchler, Christine K. Rudy, Adam C. Straub, Liqun Chi, Fang R. Chan, Jun Hu, Robert Griffiths, Nancy L. Howell, Kirsten Madsen, Boye L. Jensen, Lisa A. Palmer, Robert M. Carey, Sun-Sang J. Sung, Sandra M. Malakauskas, Brant E. Isakson, Thu H. Le
Journal: Circulation (2013)

Collectrin is an orphan member of the renin-angiotensin system and is a homolog of angiotensin-converting enzyme 2, sharing ≈50% sequence identity. Unlike angiotensin-converting enzyme 2, collectrin lacks any catalytic domain. Collectrin has been shown to function as a chaperone of amino acid transporters. In rodents, the renal expression of collectrin is increased after subtotal nephrectomy and during high-salt feeding, raising the question of whether collectrin has any direct role in blood pressure regulation.Using a susceptible genetic background, we demonstrate that deletion of collectrin results in hypertension, exaggerated salt sensitivity, and impaired pressure natriuresis. Collectrin knockout mice display impaired endothelium-dependent vasorelaxation that is associated with vascular remodeling, endothelial nitric oxide synthase uncoupling, decreased nitric oxide production, and increased superoxide generation. Treatment with Tempol, a superoxide scavenger, attenuates the augmented sodium sensitivity in collectrin knockout mice. We report for the first time that collectrin is expressed in endothelial cells. Furthermore, collectrin directly regulates l-arginine uptake and plasma membrane levels of CAT1 and y(+)LAT1 amino acid transporters in endothelial cells. Treatment with l-arginine modestly lowers blood pressure of collectrin knockout mice.Collectrin is a consequential link between the transport of l-arginine and endothelial nitric oxide synthase uncoupling in hypertension.
Use of an X-linked human neutrophil marker to estimate timing of lyonization and size of the dividing stem cell pool.
Authors: E S Buescher, D W Alling, J I Gallin
Journal: Journal of Clinical Investigation (1985)

In families with X-linked chronic granulomatous disease (CGD), heterozygous females have two stable populations of polymorphonuclear leukocytes (PMN) in their blood; one normal, the other, deficient in oxygen metabolism. The two types of PMN can be distinguished by the ability or lack of ability to reduce nitroblue tetrazolium dye. The variation in the percent normal PMN among 11 CGD heterozygotes was shown to follow a binomial distribution based on eight independent trials and a chance of success of 50%. This is consistent with the occurrence of X-chromosome inactivation (lyonization) when eight embryonic founder cells for the hematopoietic system are present. Serial determinations of the percent normal PMN in individual heterozygotes showed very limited variability (standard deviations ranged from 2.0% to 5.2%) most of which could be ascribed to experimental error. An estimate of the remaining variation (residual variance) was introduced into a well-known formula to calculate the appropriate number of pluripotent stem cells necessary to support hematopoiesis and a figure exceeding 400 was obtained. Thus, the data indicate that in humans there is a highly polyclonal system of hematopoiesis.
Neutropenia-associated ELANE mutations disrupting translation initiation produce novel neutrophil elastase isoforms
Authors: Timothy Tidwell, Jeremy Wechsler, Ramesh C. Nayak, Lisa Trump, Stephen J. Salipante, Jerry C. Cheng, Jean Donadieu, Taly Glaubach, Seth J. Corey, H. Leighton Grimes, Carolyn Lutzko, Jose A. Cancelas, Marshall S. Horwitz
Journal: Blood (2013)
OPTIMAL DURATION OF DUAL ANTIPLATELET THERAPY IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION: ONE YEAR VERSUS LONGER THAN ONE YEAR
Authors: Yoon Seok Koh, Jin Jin Kim, Ik Jun Choi, Mineok Chang, Sungmin Lim, Minkyu Kang, Byung-Hee Hwang, Donggyu Moon, Jae Gyung Kim, Eun Ho Choo, Tae-Hun Kim, Suk Min Seo, Chan Jun Kim, Pum Joon Kim, Kiyuk Chang, Wook Sung Chung, Youngkeun Ahn, Myung Ho Jeong, Keun-Ho Park, Young Joon Hong, Young Joon Hong, Doo Sun Sim, Ki-Bae Seung
Journal: Journal of the American College of Cardiology (2013)
Significance of Abnormal Phase II Response to Valsalva Maneuver in Cardiac Patients
Authors: ROBERT W. BURROUGHS, ROBERT A. BRUCE
Journal: Circulation (1956)

Abnormal responses to a standardized Valsalva maneuver have been proposed as additional criteria for heart failure. The present study was undertaken to determine the variability of these responses in normal subjects as well as frequency of abnormal responses in cardiac patients. Only phase II responses could be considered reliable for this purpose. Discrepancies between phase II responses were observed in relation to other criteria.