tbuckley/cabot-search huggingface dataset:
Screening for MODY Mutations, GAD Antibodies, and Type 1 Diabetes– Associated HLA Genotypes in Women With Gestational Diabetes Mellitus
Authors: Jianping Weng, Magnus Ekelund, Markku Lehto, Haiyan Li, Göran Ekberg, Anders Frid, Anders Åberg, Leif C. Groop, Kerstin Berntorp
Journal: Diabetes Care (2002)

OBJECTIVE—To investigate whether genetic susceptibility to type 1 diabetes or maturity-onset diabetes of the young (MODY) increases susceptibility to gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS—We studied mutations in MODY1–4 genes, the presence of GAD antibodies, and HLA DQB1 risk genotypes in 66 Swedish women with GDM and a family history of diabetes. An oral glucose tolerance test was repeated in 46 women at 1 year postpartum. RESULTS—There was no increase in type 1 diabetes–associated HLA-DQB1 alleles or GAD antibodies when compared with a group of type 2 diabetic patients (n = 82) or healthy control subjects (n = 86). Mutations in known MODY genes were identified in 3 of the 66 subjects (1 MODY2, 1 MODY3, and 1 MODY4). Of the 46 GDM subjects, 2 had diabetes (4%) and 17 had impaired glucose tolerance (IGT) (37%) at 1 year postpartum. Of the two subjects who developed manifest diabetes, one carried a MODY3 mutation (A203H in the hepatocyte nuclear factor-1α gene). There was no increase in high-risk HLA alleles or GAD antibodies in the women who had manifest diabetes or IGT at 1 year postpartum. CONCLUSIONS—MODY mutations but not autoimmunity contribute to GDM in Swedish women with a family history of diabetes and increase the risk of subsequent diabetes.
Comorbidity and lifestyle, reproductive factors, and environmental exposures associated with rheumatoid arthritis
Authors: A R. Olsson
Journal: Annals of the Rheumatic Diseases (2001)

Reversible cerebral vasoconstriction syndrome is characterised by severe headaches with or without seizures and focal neurological deficits, and constriction of cerebral arteries which resolves spontaneously in 1–3 months. It affects females slightly more than males, and mean age of onset is around 45 years. Approximately 60% of cases are secondary, mainly postpartum and after exposure to vasoactive substances. The major complications are localised cortical subarachnoid haemorrhage (22%) and parenchymal ischaemic or haemorrhagic strokes (7%) which may leave permanent sequelae. Diagnosis requires the demonstration of the "string of beads" appearance of cerebral arteries on angiography, with complete or almost complete resolution on repeat angiography 12 weeks after onset. Nimodipine seems to reduce thunderclap headaches within 48 h but has no definite effect on the haemorrhagic and ischaemic complications.
Fluid Shear Stress Attenuates Hydrogen Peroxide–Induced c-Jun NH <sub>2</sub> -Terminal Kinase Activation via a Glutathione Reductase–Mediated Mechanism
Authors: Yukihiro Hojo, Yuji Saito, Tatsuo Tanimoto, Ryan J. Hoefen, Christopher P. Baines, Kei Yamamoto, Judith Haendeler, Reto Asmis, Bradford C. Berk
Journal: Circulation Research (2002)

c-Jun NH 2 -terminal kinase (JNK) is activated by a number of cellular stimuli including reactive oxygen species (ROS). Previous studies have demonstrated that fluid shear stress (flow) inhibits cytokine-induced JNK activation in endothelial cells (ECs). In the present study, we show JNK activation by ROS in ECs and hypothesized that flow inhibits ROS-induced JNK activation in ECs via modulation of cellular protection systems against ROS. JNK was activated by 300 μmol/L hydrogen peroxide (H 2 O 2 ) in bovine lung microvascular ECs (BLMVECs) with a peak at 60 minutes after stimulation (6.3±1.2-fold increase). Preexposure of BLMVECs to physiological steady laminar flow (shear stress=12 dyne/cm 2 ) for 10 minutes significantly decreased H 2 O 2 -induced JNK activation. Thioredoxin and glutathione are cellular antioxidants that protect cells against ROS. Flow induced a significant increase in the ratio of reduced glutathione to oxidized glutathione consistent with a 1.6-fold increase in glutathione reductase (GR) activity. Preincubation of BLMVECs with the GR inhibitor, 1,3 bis-(2 chloroethyl)-1-nitrosourea, abolished the inhibitory effect of flow. In contrast, preincubation of BLMVECs with azelaic acid, a specific inhibitor for thioredoxin reductase, did not alter the effect of flow on H 2 O 2 -induced JNK activation. Overexpression of GR mimicked the effect of flow to inhibit JNK activation. These results suggest that flow activates GR, an important regulator of the intracellular redox state of glutathione, and exerts a protective mechanism against oxidative stress in endothelial cells.
There Is No Evidence for an Increase in Acute Coronary Syndromes After Short-Term Abrupt Discontinuation of Statins in Stable Cardiac Patients
Authors: Mary P. McGowan
Journal: Circulation (2004)

For a variety of reasons, many patients abruptly discontinue statin therapy. The present analysis was conducted to determine whether the risk of cardiovascular outcomes increases after withdrawal of statin therapy in a stable cardiac population.In the Treating to New Target (TNT) study, 2 doses of atorvastatin (10 and 80 mg once daily) are being used in a double-blind parallel-group design. Of the 18,468 patients screened for study participation, 16,619 entered a dietary lead-in/drug-washout period, and of these, 15,432 eligible participants began treatment with atorvastatin 10 mg/d on an open-label basis. Of the subjects who entered the dietary lead-in/drug-washout period, 57% were receiving prior statin therapy. During the 6-week drug-washout period, there were 24 primary events (defined as coronary heart disease death, nonfatal myocardial infarction, resuscitated cardiac arrest, and fatal or nonfatal stroke); throughout the subsequent 8-week open-label period, there were 31 primary events. This equated to monthly Kaplan-Meier event rates of 0.20% during washout and 0.26% in the open-label phase. Event rates were therefore similar during the 2 phases.The present analysis demonstrates that short-term discontinuation of statin therapy in stable cardiac patients apparently does not lead to a clinically important increased risk of acute coronary syndromes.
Yes and PI3K Bind CD95 to Signal Invasion of Glioblastoma
Authors: Susanne Kleber, Ignacio Sancho-Martinez, Benedict Wiestler, Alexandra Beisel, Christian Gieffers, Oliver Hill, Meinolf Thiemann, Wolf Mueller, Jaromir Sykora, Andreas Kuhn, Nina Schreglmann, Elisabeth Letellier, Cecilia Zuliani, Stefan Klussmann, Marcin Teodorczyk, Hermann-Josef Gröne, Tom M. Ganten, Holger Sültmann, Jochen Tüttenberg, Andreas von Deimling, Anne Regnier-Vigouroux, Christel Herold-Mende, Ana Martin-Villalba
Journal: Cancer Cell (2008)
Effectiveness of opportunistic brief interventions for problem drinking in a general hospital setting: systematic review
Authors: Maria J Emmen, Gerard M Schippers, Gijs Bleijenberg, Hub Wollersheim
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objective</b> To determine the effectiveness of opportunistic brief interventions for problem drinking in a general hospital setting. <b>Design</b> Systematic review. <b>Data sources</b> Medline, PsychInfo, Cochrane Library, reference lists from identified studies and review articles, and contact with experts. <b>Main outcome measure</b> Change in alcohol consumption. <b>Results</b> Eight studies were retrieved. Most had methodological weaknesses. Only one study, with a relatively intensive intervention and a short follow up period, showed a significantly large reduction in alcohol consumption in the intervention group. <b>Conclusions</b> Evidence for the effectiveness of opportunistic brief interventions in a general hospital setting for problem drinkers is still inconclusive.
A Dedication in Memoriam of Dr. Richard Skalak
Authors: Thomas C. Skalak
Journal: Annual Review of Biomedical Engineering (1999)

▪ Abstract [Formula: see text] Richard Skalak (1923–1997) played a leadership role in the formative decades of the discipline of biomedical engineering through his technical contributions in biomechanics, his educational influence on students, and his service to many developing societies and journals. But always, the distinguishing marks of his involvement with any activity or person were his generosity, respect and tolerance for others, integrity, and curiosity. These very qualities are what first brought him as a traditional engineer trained in engineering mechanics into the young field of biomedical engineering in the 1960s, and they are what led him to new approaches to cellular and molecular engineering, tissue engineering, and orthopedic biomechanics. His technical papers and lectures on blood cell mechanics, pulmonary circulation, dental implants, and tissue growth were models of clarity and often pointed the way to new areas of exploration, while his personal writings offer advice on life, academic organizations, and the pursuit of significant work. He would be deeply appreciative that this first volume of the Annual Review of Biomedical Engineering is dedicated to his memory.
Examination of the Relationship of Renin Release to Hypertension Produced in the Rabbit by Renal-Artery Constriction
Authors: W. S. PEART, J. I. S. ROBERTSON, D. G. GRAHAME-SMITH
Journal: Circulation Research (1961)

Plasma samples taken from the renal veins of rabbits hypertensive following renal-artery constriction were examined for evidence of increased renin content. No increase in the activity of the renal-vein samples was found as compared with plasma obtained from other sites in these rabbits, or with samples taken from unoperated animals. By contrast, renin infused into the renal veins of rabbits to give comparable elevation of the arterial pressure was, in all cases, detected. The experimental findings are discussed in relation to current views of the role of renin in experimental hypertension in the rabbit.
Correct and incorrect vertebrate phylogenies obtained by the entire mitochondrial DNA sequences
Authors: N. Takezaki, T. Gojobori
Journal: Molecular Biology and Evolution (1999)

Concatenated sequences of all protein-coding genes in mitochondria recovered a known phylogeny of 11 vertebrate species correctly with statistical significance. However, when it was rooted by lampreys or sea urchins, the root of the vertebrate tree was placed between the mammal cluster and the chicken-frog-fish cluster or between the mammal-chicken cluster and the frog-fish cluster, depending on the tree-making method used. Although the frog-fish or chicken-frog-fish cluster was biologically incorrect, it was again supported with a significantly high bootstrap value. In this study, we investigated the reasons why this happened. It has been suggested that an incorrect phylogeny may be constructed due to a change of amino acid composition in different lineages or due to homoplasies at sites with hydrophobic amino acids. However, our results indicated that these were not the causes of the incorrect rooting of the vertebrate tree. Rather, it was important to take into account an extensive rate variation across sites and different probabilities of substitution among different amino acids. The substitution rates for mitochondrial sequences vary considerably for different vertebrate lineages. In such a case, it is known to be important to use the model that reflects the actual substitution probability to obtain a correct tree topology. The correct rooting of the vertebrate tree was recovered when rate variation across sites was properly accounted for.
2011 ACCF/AHA Focused Update of the Guidelines for the Management of Patients With Unstable Angina/ Non–ST-Elevation Myocardial Infarction (Updating the 2007 Guideline)
Authors: R. Scott Wright, Jeffrey L. Anderson, Cynthia D. Adams, Charles R. Bridges, Donald E. Casey, Steven M. Ettinger, Francis M. Fesmire, Theodore G. Ganiats, Hani Jneid, A. Michael Lincoff, Eric D. Peterson, George J. Philippides, Pierre Theroux, Nanette K. Wenger, James Patrick Zidar
Journal: Circulation (2011)
Lecture notes on human physiology.: J J Bray, P A Cragg, A D C Macknight, R G Mills. (Pp 610; pound19.95.) Oxford: Blackwell Science Ltd, 1999. ISBN 0-86542-775-5. All books are available from Blackwell Science Ltd, Osney Mead, Oxford OX2 0EL. Tel: 01865 206206, Fax: 01865 721205.
Authors: Mark De Ste Croix
Journal: British Journal of Sports Medicine (2000)

My immediate impressions when opening this text were that it is comprehensively written but at the same time may appear daunting, especially to undergraduate students. However, on reading the text, it becomes readily apparent that the subject matter is well described in a digestible manner. The flow of the text is aided by the fact that no references are included in the text. …
Gefitinib-Sensitive Mutations of the Epidermal Growth Factor Receptor Tyrosine Kinase Domain in Chinese Patients with Non–Small Cell Lung Cancer
Authors: Xin Lin Mu, Long Yun Li, Xiao Tong Zhang, Men Zhao Wang, Rui E. Feng, Quan Cai Cui, Hai Sheng Zhou, Bing Qing Guo
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Studies have shown that mutations in the epidermal growth factor receptor (EGFR) tyrosine kinase domain are associated with response of lung cancer to gefitinib (Iressa, AstraZeneca Corp., Shanghai, China). A higher incidence of EGFR mutation was observed in non–small cell lung cancer (NSCLC) patients of Japanese origin compared with those of American origin. However, no data about such mutations in Chinese patients with NSCLC could be obtained. Methods: Primary NSCLC tissues were obtained for analysis of mutations in exons 18 to 21 of EGFR from a total of 76 patients, of whom 54 did not receive gefitinib therapy and 22 did. PCR products were sequenced directly and mutations were confirmed by an independent PCR and sequence analysis. All types of mutation were cloned and sequenced. Results: A total of 10 types of mutation were found in the series of patients, including two different silent mutations in exon 20 from 11 patients. More than half of the silent mutations (6 of 11) in exon 20 coexisted with other mutations. Mutations were more frequent in adenocarcinoma (17 of 35; 48.6%) compared with squamous carcinoma (1 of 19; 5.3%) among untreated patients. Similar mutations were observed in all seven gefitinib-treated patients with partial response, and no mutations were detected in all eight patients with progressive disease (P &amp;lt; 0.001), except two silent mutations. Three mutations were observed in seven patients with stable disease. Conclusions: Mutations in the epidermal growth factor receptor tyrosine kinase domain in lung adenocarcinomas from Chinese patients were more frequent than reported previously in lung adenocarcinomas from American patients. Such mutations were well correlated with tumor response to gefitinib.
Radiation Exposure, the ATM Gene, and Contralateral Breast Cancer in the Women's Environmental Cancer and Radiation Epidemiology Study
Authors: Jonine L. Bernstein, Robert W. Haile, Marilyn Stovall, John D. Boice, Roy E. Shore, Bryan Langholz, Duncan C. Thomas, Leslie Bernstein, Charles F. Lynch, Jorgen H. Olsen, Kathleen E. Malone, Lene Mellemkjaer, Anne-Lise Borresen-Dale, Barry S. Rosenstein, Sharon N. Teraoka, Anh T. Diep, Susan A. Smith, Marinela Capanu, Anne S. Reiner, Xiaolin Liang, Richard A. Gatti, Patrick Concannon
Journal: JNCI Journal of the National Cancer Institute (2010)

Ionizing radiation is a known mutagen and an established breast carcinogen. The ATM gene is a key regulator of cellular responses to the DNA damage induced by ionizing radiation. We investigated whether genetic variants in ATM play a clinically significant role in radiation-induced contralateral breast cancer in women. The Women's Environmental, Cancer, and Radiation Epidemiology Study is an international population-based case–control study nested within a cohort of 52 536 survivors of unilateral breast cancer diagnosed between 1985 and 2000. The 708 case subjects were women with contralateral breast cancer, and the 1397 control subjects were women with unilateral breast cancer matched to the case subjects on age, follow-up time, registry reporting region, and race and/or ethnicity. All women were interviewed and underwent full mutation screening of the entire ATM gene. Complete medical treatment history information was collected, and for all women who received radiotherapy, the radiation dose to the contralateral breast was reconstructed using radiotherapy records and radiation measurements. Rate ratios (RRs) and corresponding 95% confidence intervals (CIs) were estimated by using multivariable conditional logistic regression. All P values are two-sided. Among women who carried a rare ATM missense variant (ie, one carried by <1% of the study participants) that was predicted to be deleterious, those who were exposed to radiation (mean radiation exposure = 1.2 Gy, SD = 0.7) had a statistically significantly higher risk of contralateral breast cancer compared with unexposed women who carried the wild-type genotype (0.01–0.99 Gy: RR = 2.8, 95% CI = 1.2 to 6.5; ≥1.0 Gy: RR = 3.3, 95% CI = 1.4 to 8.0) or compared with unexposed women who carried the same predicted deleterious missense variant (0.01–0.99 Gy: RR = 5.3, 95% CI = 1.6 to 17.3; ≥1.0 Gy: RR = 5.8, 95% CI = 1.8 to 19.0; Ptrend = .044). Women who carry rare deleterious ATM missense variants and who are treated with radiation may have an elevated risk of developing contralateral breast cancer. However, the rarity of these deleterious missense variants in human populations implies that ATM mutations could account for only a small portion of second primary breast cancers.
Malignant progression of precancerous lesions of the uterine cervix following biological DMARD therapy in patients with arthritis
Authors: René Cordtz, Lene Mellemkjær, Bente Glintborg, Merete Lund Hetland, Lene Dreyer
Journal: Annals of the Rheumatic Diseases (2015)

Patients with rheumatoid arthritis (RA) are more frequent chronic carriers of high-risk human papilloma virus (HPV) strains compared with the background population—an important risk factor for developing cervical cancer—and patients with RA have an increased risk of high-grade cervical dysplasia (CD) and cervical cancer.1–3 Little is known about the safety of biological disease-modifying antirheumatic drug (bDMARD) treatment in arthritis patients with a history of premalignant lesions.

We aimed to investigate how often female patients with inflammatory arthritis (RA, ankylosing spondylitis, psoriatic arthritis or other) and a history of premalignant lesions of the uterine cervix developed cervical cancer or another HPV-associated cancer according to ever versus never exposure to bDMARDs.

The nationwide Danish DANBIO Registry started in 2000 and covers >90% of adults with rheumatological disease treated with bDMARDs in routine care.4 Since 2005, patients not treated with bDMARDs have also been registered. We linked 15 238 female patients identified in DANBIO …
Perceptual variation in grading hand, hip and knee radiographs: observations based on an Australian Twin Registry study of osteoarthritis
Authors: N. Bellamy, P. Tesar, D. Walker, A. Klestov, K. Muirden, P. Kuhnert, K.-A. Do, L. O'Gorman, N. Martin
Journal: Annals of the Rheumatic Diseases (1999)

<h3>OBJECTIVE</h3> The radiographic diagnosis of osteoarthritis (OA) in the peripheral skeleton is dependent on the skilled examination of several morphological characteristics of the condition as visualised on plain radiographs. However, the process is perceptual and generally enhanced by comparison against photographic standards. This study assessed the intra-rater and inter-rater reliability of radiologists experienced in reporting hand, hip and knee films derived from a community-based sample when using the photographic atlas recently developed by Burnett<i>et al</i>. <h3>METHODS</h3> This study was part of a multifaceted diagnostics protocol, evaluating methodological issues, in the conduct of genetic research in osteoarthritis. From a cohort of 118 twin pairs, registered with the Australian Twins Registry (ATR), standard clinical examinations were performed on 74 complete and 11 incomplete pairs of twins over age 50 years, followed by standard AP hand, AP pelvis and AP standing radiographs of the knees. The pairs were selected both to represent twin pairs who had previously self reported a diagnosis of OA, as well as those who had not. Radiologists read the films blind to the original self reported diagnosis and without reference to their pairing. The films were read by comparison against photographic standards and were scored according to specific features. All films were read independently by two consultant radiologists blind to one another9s assessments, and selected films were thereafter assigned for rereading. Inter-rater and intra-rater agreement were different for different features, different anatomic areas, and, for the former, were different for the two radiologists. <h3>RESULTS</h3> Inter-rater agreement was different for different anatomic areas, different radiographic features, and the two radiologists. Intra-rater agreement for the presence or absence of OA was as follows: actual observed agreement = 0.79 to 0.97 and 0.83 to 0.98; adjusted κ statistic = 0.58 to 0.94 and 0.67 to 0.96; inter-rater agreement was as follows: actual observed agreement = 0.77 to 0.97; adjusted κ statistic = 0.54 to 0.94. Agreement was generally high in most of the principal target joints for OA: DIP, PIP, 1st CMC, hip and knee. <h3>CONCLUSIONS</h3> Although assessor agreement was not perfect, it is concluded that for genetic epidemiology purposes, while duplicate assessments may be advantageous, it is possible for radiographs to be examined accurately by a single experienced assessor. However, for less experienced assessors independent examinations should be made by at least two assessors and either a consensus reached on disparate examinations or an algorithm developed to adjudicate any discrepancies.