tbuckley/cabot-search huggingface dataset:
A common atopy‐associated variant in the Th2 cytokine locus control region impacts transcriptional regulation and alters <scp>SMAD</scp>3 and <scp>SP</scp>1 binding
Authors: A. Kretschmer, G. Möller, H. Lee, H. Laumen, C. von Toerne, K. Schramm, H. Prokisch, S. Eyerich, S. Wahl, H. Baurecht, A. Franke, M. Claussnitzer, K. Eyerich, A. Teumer, L. Milani, N. Klopp, S. M. Hauck, T. Illig, A. Peters, M. Waldenberger, J. Adamski, E. Reischl, S. Weidinger
Journal: Allergy (2014)

Abstract Background Type 2 immune responses directed by T h2 cells and characterized by the signature cytokines IL 4, IL 5, and IL 13 play major pathogenic roles in atopic diseases. Single nucleotide polymorphisms in the human T h2 cytokine locus in particular in a locus control region within the DNA repair gene RAD 50 , containing several RAD 50 DN ase1‐hypersensitive sites ( RHS ), have been robustly associated with atopic traits in genome‐wide association studies ( GWAS ). Functional variants in IL 13 have been intensely studied, whereas no causative variants for the IL 13 ‐independent RAD 50 signal have been identified yet. This study aimed to characterize the functional impact of the atopy‐associated polymorphism rs2240032 located in the human RHS 7 on cis ‐regulatory activity and differential binding of transcription factors. Methods Differential transcription factor binding was analyzed by electrophoretic mobility shift assays ( EMSA s) with J urkat T ‐cell nuclear extracts. Identification of differentially binding factors was performed using mass spectrometry ( LC ‐ MS / MS ). Reporter vector constructs carrying either the major or minor allele of rs2240032 were tested for regulating transcriptional activity in J urkat and H e L a cells. Results The variant rs2240032 impacts transcriptional activity and allele‐specific binding of SMAD 3, SP 1, and additional putative protein complex partners. We further demonstrate that rs2240032 is located in an RHS 7 subunit which itself encompasses repressor activity and might be important for the fine‐tuning of transcription regulation within this region. Conclusion The human RHS 7 critically contributes to the regulation of gene transcription, and the common atopy‐associated polymorphism rs2240032 impacts transcriptional activity and transcription factor binding.
Prenatal Exposure to Carbon Monoxide Affects Postnatal Cellular Electrophysiological Maturation of the Rat Heart
Authors: Laura Sartiani, Elisabetta Cerbai, Giuseppe Lonardo, Petra DePaoli, Maria Tattoli, Raffaele Cagiano, Maria Rosaria Carratù, Vincenzo Cuomo, Alessandro Mugelli
Journal: Circulation (2004)

Maternal smoking is an independent risk factor for sudden infant death syndrome (SIDS). Carbon monoxide (CO) is a major component of smoke. No information is available about the effect of CO and/or smoking on postnatal maturation of the heart. The aim of this study was to investigate the effect of prenatal exposure to CO on cellular electrophysiological maturation in male Wistar rats.The patch-clamp technique was used to measure action potential (AP) and ionic currents (I(to) and I(Ca,L)) from rat ventricular myocytes. During growth, AP duration measured at -20 and -50 mV (APD(-)(20) and APD(-)(50)) decreased progressively in both groups; the process was significantly delayed in rats exposed prenatally to 150 ppm CO: At 4 weeks, APD(-)(20) and APD(-)(50) were 89.5+/-18.2 and 147.7+/-24.5 ms in CO (n=13) and 35.6+/-4.5 and 77.8+/-8.3 ms in control rats (Ctr; n=14; P<0.01 and P<0.05, respectively) and normalized at 8 weeks. At 4 weeks, the density of I(Ca,L) was significantly higher (21.3+/-1.6 pA/pF, n=17, versus 15.9+/-1.6 pA/pF, n=22; P<0.05) and the density of I(to) significantly lower (9.6+/-1.5, n=22, versus 15.2+/-2.2 pA/pF, n=19; P<0.01) in CO than in Ctr and normalized thereafter.Prenatal CO exposure affects the physiological shortening of APD in neonatal rats. We speculate that a prolonged myocyte repolarization induced by prenatal exposure to smoke may establish a period of vulnerability for life-threatening arrhythmias in infancy.
Coronary Angiographic Characteristics of Patients With Permanent Artificial Pacemakers
Authors: Morris Mosseri, Tami Izak, Shimon Rosenheck, Chaim Lotan, Yoseph Rozenman, Einat Zolti, Dan Admon, Mervyn S. Gotsman
Journal: Circulation (1997)

Background The cause of severe cardiac conduction disturbances is often uncertain. The aim of this study was to examine a group of patients with permanent pacemakers who underwent coronary arteriography to determine the extent of coronary atherosclerotic disease that might be responsible for the conduction disturbances. Methods and Results Forty-three consecutive patients with a permanent pacemaker and 36 matched control patients were investigated. The coronary angiographic study included measurement of diameter and stenosis severity, qualitative assessment of flow, and classification of pathological anatomy, particularly the blood supply to territories supplying the different segments of the conduction system. Among 43 patients with a permanent pacemaker, 27 had ischemic heart disease (17 after coronary artery bypass graft surgery). The conduction disturbance was infranodal in 28 patients, sinus nodal in 6, AV nodal in 4, and complete AV block of unspecified origin in 5. Patients with permanent pacemakers had a coronary artery pathology compromising blood flow to the septal branches and the right coronary artery (type IV anatomy). This pattern was significantly different from the matched control patients, in whom the most prevalent coronary anatomy was the combination of right coronary artery with distal left anterior descending artery (not involving the septal branches) lesions ( P =.007). Conclusions Patients with coronary artery disease and severe conduction disturbances that require implantation of permanent pacemakers are more likely to have a specific pathological coronary anatomy that combines a compromised blood flow to the septal branches of the left anterior descending artery with right coronary artery lesions. The location of lesions in the coronary tree rather than severe diffuse atherosclerosis appears to be responsible for the conduction disturbances.
"THE CONTROL OF TRACHOMA"
Authors: Orlyn S. Phillips
Journal: JAMA (1923)

<h3>To the Editor:</h3> —In further reference to the prevalence of trachoma in the United States, I will say that I examined 7,000 troops at Camp MacArthur, Texas, in 1918, among whom I found fifty well developed cases of this disease. I might add that these men were from Missouri and Texas, and the probabilities are that the average is a little high, trachoma being prevalent in the Ozark region of Missouri.
The presumptive CDR3 regions of both T cell receptor alpha and beta chains determine T cell specificity for myoglobin peptides.
Authors: J S Danska, A M Livingstone, V Paragas, T Ishihara, C G Fathman
Journal: The Journal of Experimental Medicine (1990)

The T cell receptor alpha/beta (TCR-alpha/beta) is encoded by variable (V), diversity (D), joining (J), and constant (C) segments assembled by recombination during thymocyte maturation to produce a heterodimer that imparts antigenic specificity to the T cell. Unlike immunoglobulins (Igs), which bind free antigen, the ligands of TCR-alpha/beta are cell surface complexes of intracellularly degraded antigens (i.e., peptides) bound to and presented by polymorphic products of the major histocompatibility complex (MHC). Therefore, antigen recognition by T cells is defined as MHC restricted. A model has been formulated based upon the similarity between TCR-alpha/beta V region and Ig Fab amino acid sequences, and the crystal structure of the MHC class I and Ig molecules. This model predicts that the complementarity determining regions (CDR) 1 and 2, composed of TCR V alpha and V beta segments, primarily contact residues of the MHC alpha helices, whereas V/J alpha and V/D/J beta junctional regions (the CDR3 equivalent) contact the peptide in the MHC binding groove. Because polymorphism in MHC proteins is limited relative to the enormous diversity of antigenic peptides, the TCR may have evolved to position the highly diverse junctional residues (CDR3), where they have maximal contact with antigen bound in the MHC peptide groove. Here, we demonstrate a definitive association between CDR3 sequences in both TCR alpha and beta chains, and differences in recognition of antigen fine specificity using a panel of I-Ed-restricted, myoglobin-reactive T cell clones. Acquisition of these data relied in part upon a modification of the polymerase chain reaction that uses a degenerate, consensus primer to amplify TCR alpha chains without foreknowledge of the V alpha segments they utilize.
Cuts in NHS funding are spared in the budget, but staff pay suffers
Authors: N. Timmins
Journal: BMJ (2009)

The NHS received some qualified good news in the Chancellor’s pre-budget report on 9 December. Rather than the cash freeze that was anticipated the bulk of NHS spending is to rise in line with inflation for the two years starting in 2011. NHS staff, however, face a prolonged period of below inflation pay rises to help fund the rise in spending. 

NHS pensions are also likely to be hit by the changes and all those earning more than £20 000 a year will also have to pay higher national insurance contributions.

The chancellor Alistair Darling announced that 95% of …
Splenic Marginal Zone Lymphoma: Transformation to Diffuse Large B-Cell Lymhoma With Isolated Cerebral Manifestation
Authors: Nils H. Thoennissen, Kathy Keyvani, Hans U. Voelker, Janbernd Bremer, Utz Krug, Carsten Müller-Tidow, Peter Koch, Hans K. Müller-Hermelink, Wolfgang E. Berdel
Journal: Journal of Clinical Oncology (2008)
SNP array analysis of tyrosine kinase inhibitor-resistant chronic myeloid leukemia identifies heterogeneous secondary genomic alterations
Authors: Daniel Nowak, Seishi Ogawa, Markus Müschen, Motohiro Kato, Norihiko Kawamata, Antonie Meixel, Verena Nowak, Han S. Kim, Sharon Kang, Ronald Paquette, Mi-Sook Chang, Nils H. Thoennissen, Max Mossner, Wolf-Karsten Hofmann, Alexander Kohlmann, Tamara Weiss, Torsten Haferlach, Claudia Haferlach, H. Phillip Koeffler
Journal: Blood (2009)
Left Ventricular Electromechanical Mapping to Assess Efficacy of phVEGF <sub>165</sub> Gene Transfer for Therapeutic Angiogenesis in Chronic Myocardial Ischemia
Authors: Peter R. Vale, Douglas W. Losordo, Charles E. Milliken, Michael Maysky, Darryl D. Esakof, James F. Symes, Jeffrey M. Isner
Journal: Circulation (2000)

NOGA left ventricular (LV) electromechanical mapping (EMM) can be used to distinguish among infarcted, ischemic, and normal myocardium. We investigated the use of percutaneous LV EMM to assess the efficacy of myocardial gene transfer (GTx) of naked plasmid DNA encoding for vascular endothelial growth factor (phVEGF(165)), administered during surgery by direct myocardial injection in patients with chronic myocardial ischemia.A total of 13 consecutive patients (8 men, mean age 60.1+/-2. 3 years) with chronic stable angina due to angiographically documented coronary artery disease, all of whom had failed conventional therapy (drugs, PTCA, and/or CABG), were treated with direct myocardial injection of phVEGF(165) via a minithoracotomy. Foci of ischemic myocardium were identified on LV EMM by preserved viability associated with an impairment in linear local shortening. Myocardial viability, defined by mean unipolar and bipolar voltage recordings >/=5 and >/=2 mV, respectively, did not change significantly after GTx. Analysis of linear local shortening in areas of myocardial ischemia, however, disclosed significant improvement after (15.26+/-0.98%) versus before (9.94+/-1.53%, P:=0. 004) phVEGF(165) GTx. The area of ischemic myocardium was consequently reduced from 6.45+/-1.37 cm(2) before GTx to 0.95+/-0. 41 cm(2) after GTx (P:=0.001). These findings corresponded to improved perfusion scores calculated from single-photon emission CT-sestamibi myocardial perfusion scans recorded at rest (7.4+/-2.1 before GTx versus 4.5+/-1.4 after GTx, P:=0.009) and after pharmacological stress (12.8+/-2.7 before GTx versus 8.5+/-1.7 after GTx, P:=0.047).The results of EMM constitute objective evidence that phVEGF(165) GTx augments perfusion of ischemic myocardium. These findings, together with reduction in the size of the defects documented at rest by serial single-photon emission CT-sestamibi imaging, suggest that phVEGF(165) GTx may successfully rescue foci of hibernating myocardium.
Rapidly progressive bronchiolitis obliterans with organizing pneumonia.
Authors: A J Cohen, T E King, G P Downey
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Bronchiolitis obliterans with organizing pneumonia (BOOP) is a distinct clinical pathologic syndrome. Most patients experience a good response to therapy, and death from progressive BOOP is uncommon. This report describes the clinical features, etiologic factors, pathologic findings, and outcome of 10 patients with rapidly progressive BOOP that was characterized by severe respiratory failure. The major clinical manifestations were dyspnea, cough, fever, crackles on chest examination, and hypoxemia at rest. Underlying conditions or exposures included connective-tissue disease, exposure to birds, and chronic nitrofurantoin therapy. All patients had the characteristic histopathologic findings of BOOP. However, at autopsy in six patients, the predominant histologic pattern was that of alveolar septal inflammation and fibrotic honeycombing. Seven patients died and three patients survived but had persistent pulmonary dysfunction despite aggressive care. In two patients BOOP has progressed, with severe chronic respiratory decompensation. Thus, there is a subset of patients with BOOP who present with a fulminant course leading to death or chronic severe fibrosis and marked impairment of lung function. In addition, the histologic picture of BOOP may be a manifestation of early lung injury that can resolve or progress rapidly to alveolar septal inflammation, end-stage fibrosis, and honeycombing.
Adrenal Cortex: Transactions of the Second Conference, November 16-17, 1950, New York, N. Y
Authors: Elaine P. Ralli
Journal: JAMA (1952)

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
The Study and Treatment of Alcoholism
Authors: David J. Myerson
Journal: New England Journal of Medicine (1957)

THIS review is designed to put into perspective the present multidisciplined approach to the problem of alcoholism. Emphasis is placed on trends and their development rather than on details. The reason for this design is twofold: several excellent medical reviews are already available,1 , 2 to which nothing important can be added; and, more significantly, despite the important medical aspects of the problem of alcoholism, a study of the historical development of trends and attitudes reveals that alcoholism is by no means only a medical problem. Rather, it is an age-old, multidetermined and serious disorder with facets that reach deeply into the . . .
Enhancement of cell retention and functional benefits in myocardial infarction using human amniotic-fluid stem-cell bodies enriched with endogenous ECM
Authors: Wen-Yu Lee, Hao-Ji Wei, Wei-Wen Lin, Yi-Chun Yeh, Shiaw-Min Hwang, Jiun-Jie Wang, Ming-Song Tsai, Yen Chang, Hsing-Wen Sung
Journal: Biomaterials (2011)
The United States and Canada: Different Approaches to Health Care
Authors: Arnold S. Relman
Journal: New England Journal of Medicine (1986)

Most people would agree that the health care system in wealthy, technically advanced countries like the United States and Canada ought to have as its primary objective access of all citizens to adequate, mainstream care, at a cost the national economy can afford. Knowledgeable observers, who understand how important physicians are to the quality and innovativeness of medical services, would probably add another important objective — i.e., preservation of the morale and professional traditions of the doctors.Despite their common border and shared culture, the United States and Canada have taken quite different roads in seeking these ends. In the . . .
Drug-Induced Esophagitis
Authors: J. Michael Hayes
Journal: JAMA (1985)

To the Editor.—  We recently read with interest the article by Amendola and Spera, 1 who reported a case of doxycycline-induced esophagitis. This condition was apparently due to prolonged mucosal contact of the doxycycline capsule.  The case commentary lists those drugs known to have been reported to cause esophagitis. However, not included in the list is theophylline, which has been reported to cause esophageal ulceration as well. 2 In the particular case described, the tablet was taken without water and subsequently caused an esophageal ulceration 25 cm from the incisiors, secondary to prolonged mucosal contact. The patient was subsequently treated with hourly antacids and symptoms abated within one week.
Higher potency statins and the risk of new diabetes: multicentre, observational study of administrative databases
Authors: C. R. Dormuth, K. B. Filion, J. M. Paterson, M. T. James, G. F. Teare, C. B. Raymond, E. Rahme, H. Tamim, L. Lipscombe
Journal: BMJ (2014)

<b>Objective</b> To evaluate the incremental increase in new onset diabetes from higher potency statins compared with lower potency statins when used for secondary prevention. <b>Design</b> Eight population based cohort studies and a meta-analysis. <b>Setting</b> Six Canadian provinces and two international databases from the UK and US. <b>Participants</b> 136&nbsp;966 patients aged ≥40 years newly treated with statins between 1 January 1997 and 31 March 2011. <b>Methods</b> Within each cohort of patients newly prescribed a statin after hospitalisation for a major cardiovascular event or procedure, we performed as-treated, nested case-control analyses to compare diabetes incidence in users of higher potency statins with incidence in users of lower potency statins. Rate ratios of new diabetes events were estimated using conditional logistic regression on different lengths of exposure to higher potency versus lower potency statins; adjustment for confounding was achieved using high dimensional propensity scores. Meta-analytic methods were used to estimate overall effects across sites. <b>Main outcome measures</b> Hospitalisation for new onset diabetes, or a prescription for insulin or an oral antidiabetic drug. <b>Results</b> In the first two years of regular statin use, we observed a significant increase in the risk of new onset diabetes with higher potency statins compared with lower potency agents (rate ratio 1.15, 95% confidence interval 1.05 to 1.26). The risk increase seemed to be highest in the first four months of use (rate ratio 1.26, 1.07 to 1.47). <b>Conclusions</b> Higher potency statin use is associated with a moderate increase in the risk of new onset diabetes compared with lower potency statins in patients treated for secondary prevention of cardiovascular disease. Clinicians should consider this risk when prescribing higher potency statins in secondary prevention patients.
A CASE OF HEART GUMMATA, WITH SUDDEN DEATH.
Authors: F. GOLDFRANK
Journal: JAMA (1905)

On Jan. 10, 1905, Professor Dittrich, head of the Department of Legal Medicine in the German University in Prague, performed an autopsy on a woman aged 25, who had died suddenly during the night of January 8. The report from the police department stated merely that the woman had "heart disease" for some time. The heart revealed such an interesting condition that Professor Dittrich at once sent it to the pathologic institute for further study. <h3>AUTOPSY REPORT.</h3> The findings at the autopsy, according to the data kindly furnished by Professor Dittrich, were, briefly, as follows: <h3>General Appearance.</h3> —The body was of medium height, stout but well built and well nourished. The brain was normal, somewhat anemic. The lungs were perfectly normal, no sign of tuberculosis being found; some of the bronchial lymph glands, however, showed the presence of calcified nodules. The liver and spleen were hyperemic, otherwise normal. The gastrointestinal
Abstract 2609: Addition of ER and PTEN, but not cytokeratins, aids identification for BRCA1 carriers in Malaysian breast cancer patients
Authors: Sze-Yee Phuah, Lai Meng Looi, Anthony Rhodes, Sarah Dean, Nur Aishah Mohd Taib, Cheng Har Yip, Soo-Hwang Teo
Journal: Cancer Research (2012)

Abstract Background: Given that BRCA1 carriers are more likely to develop triple negative breast cancers (TNBC) and that current risk assessment models underestimate BRCA carriers in Asian populations, we have sought to determine the prevalence of BRCA mutations amongst TNBC patients and whether addition of pathological features improves the sensitivity of the Manchester scoring method of BRCA risk assessment. Methods: A total of 399 patients from the Malaysian Breast Cancer Genetic Study were fully analysed for BRCA1 and BRCA2 mutations, including 101 patients with TNBC. Pathological features, including estrogen receptor (ER) and PTEN status were assessed and included in a modified Manchester scoring method. Results: Our study in an Asian series of triple negative breast cancer patients has demonstrated that 22% [22/101] of patients have germline mutations in BRCA1 [18/101] and BRCA2 [4/101]. We find that amongst patients who were diagnosed with breast cancer aged 36-50 but with no family history of breast or ovarian cancer, the prevalence of BRCA mutations was similar amongst those who developed triple negative breast cancer (7%) and non-TNBC (7%). By contrast, in two other groups of patients (a) those who were diagnosed with breast cancer β35 years old with no family history of these cancers, and (b) those with family history of breast cancer, the prevalence of mutations was higher in those with TNBC compared to those with non-TNBC [29% and 11%; p=0.07; and 40% and 14%; p=0.001 respectively]. Furthermore, we find that incorporation of estrogen-receptor status improves the sensitivity of the Manchester Scoring method [38% to 62%] and in particular, incorporation of the status of PTEN, further improves sensitivity [43% to 100%]. Conclusion: We find that TNBC is an important criteria for highlighting patients who may benefit from genetic testing, but that this may be most useful for individuals with early onset breast cancer (≥35 years old) or with family history of cancers. Furthermore, addition of ER and PTEN status improves the sensitivity of the Manchester scoring method and may be particularly important in the Asian context when family history is often inaccurately reported. 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 2609. doi:1538-7445.AM2012-2609