tbuckley/cabot-search huggingface dataset:
An Association Between Amino Acid Position 74 of HLA–DRB1 and Anti–Citrullinated Protein Antibody Levels in Japanese Patients With Anti–Citrullinated Protein Antibody–Positive Rheumatoid Arthritis
Authors: Chikashi Terao, Akari Suzuki, Katsunori Ikari, Yuta Kochi, Koichiro Ohmura, Masaki Katayama, Shuichiro Nakabo, Natsuki Yamamoto, Taku Suzuki, Takuji Iwamoto, Kimiko Yurugi, Yasuo Miura, Taira Maekawa, Kiyoshi Takasugi, Michiaki Kubo, Hiroh Saji, Atsuo Taniguchi, Shigeki Momohara, Kazuhiko Yamamoto, Hisashi Yamanaka, Tsuneyo Mimori, Fumihiko Matsuda
Journal: Arthritis & Rheumatology (2015)

Objective Anti–citrullinated protein antibodies (ACPAs) are highly specific to rheumatoid arthritis (RA), and strong associations between HLA–DRB1 alleles and ACPA levels have been detected in RA patients. We undertook this study to elucidate the associations between particular amino acid positions in HLA–DRB1 and ACPA levels in patients with RA. Methods We analyzed ACPA data on a total of 4,371 Japanese ACPA‐positive RA patients in whom HLA–DRB1 allele genotyping had been performed. Generalized linear regression analysis and omnibus testing were carried out to determine associations of HLA–DRB1 alleles, amino acid residues, or amino acid positions with levels of ACPA. Results HLA–DRB1*09:01 and HLA–DR15 were confirmed to be associated with ACPA levels. HLA–DRB1*08:03 and DRB1*14:06 were associated with reduced and increased ACPA levels, respectively. We detected a strong association between ACPA levels and amino acid position 74 ( P = 1.9 × 10 −51 ). The association was mainly conferred by alanine residue ( P = 4.5 × 10 −51 ). After adjustment for position 74, amino acid positions 60 and 57 were found to be associated with ACPA levels. Amino acid positions 74 and 57 had previously been reported to be associated with susceptibility to ACPA‐positive RA in Asians. Combinations of the amino acid residues at position 74 and position 60 or 57 could induce improvement in Akaike's information criterion comparable to that induced by the 5 significant HLA–DRB1 alleles (HLA–DRB1*08:03, DRB1*09:01, DRB1*14:06, DRB1*15:01, and DRB1*15:02). Conclusion Amino acid position 74 in HLA–DRB1 is strongly associated with ACPA levels in ACPA‐positive RA, as well as with RA susceptibility. The mechanisms of ACPA production and susceptibility to ACPA‐positive RA seem to partly overlap.
International Olympic Committee consensus statement on thermoregulatory and altitude challenges for high-level athletes
Authors: MF Bergeron, R Bahr, P Bärtsch, L Bourdon, JAL Calbet, KH Carlsen, O Castagna, J González-Alonso, C Lundby, RJ Maughan, G Millet, M Mountjoy, S Racinais, P Rasmussen, AW Subudhi, AJ Young, T Soligard, L Engebretsen
Journal: British Journal of Sports Medicine (2012)

Challenging environmental conditions, including heat and humidity, cold, and altitude, pose particular risks to the health of Olympic and other high-level athletes. As a further commitment to athlete safety, the International Olympic Committee (IOC) Medical Commission convened a panel of experts to review the scientific evidence base, reach consensus, and underscore practical safety guidelines and new research priorities regarding the unique environmental challenges Olympic and other international-level athletes face. For non-aquatic events, external thermal load is dependent on ambient temperature, humidity, wind speed and solar radiation, while clothing and protective gear can measurably increase thermal strain and prompt premature fatigue. In swimmers, body heat loss is the direct result of convection at a rate that is proportional to the effective water velocity around the swimmer and the temperature difference between the skin and the water. Other cold exposure and conditions, such as during Alpine skiing, biathlon and other sliding sports, facilitate body heat transfer to the environment, potentially leading to hypothermia and/or frostbite; although metabolic heat production during these activities usually increases well above the rate of body heat loss, and protective clothing and limited exposure time in certain events reduces these clinical risks as well. Most athletic events are held at altitudes that pose little to no health risks; and training exposures are typically brief and well-tolerated. While these and other environment-related threats to performance and safety can be lessened or averted by implementing a variety of individual and event preventative measures, more research and evidence-based guidelines and recommendations are needed. In the mean time, the IOC Medical Commission and International Sport Federations have implemented new guidelines and taken additional steps to mitigate risk even further.
Evaluation of human monoclonal antibodies to HCV in the HCV-trimera model: a mouse model for HCV infection
Authors: O. Nussbaum, E. Ilan, R. Eren, A. Zauberman, Y. Porat, L. Neville, Y. Arazi, G. Livneh, S. Shavit, K. Hadlock, S. Foung, S. Dagan
Journal: Journal of Hepatology (2001)
Effect of acidosis on intracellular pH and calcium concentration in the newborn and adult rabbit myocardium.
Authors: T Nakanishi, M Seguchi, T Tsuchiya, S Yasukouchi, A Takao
Journal: Circulation Research (1990)

This study investigated developmental changes in the effect of acidosis on intracellular pH (pHi) and [Ca]i in the isolated heart and isolated myocyte preparations. The whole heart or myocytes of newborn (5-7 days old) and adult rabbits were loaded with the fluorescent pH indicator 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF) or calcium indicator fura-2. Left ventricular pressure in the isolated heart preparation and the magnitude of cell contraction in the single-cell preparation were monitored. The heart and single cell were illuminated with excitation lights (340 and 380 nm, respectively, for fura-2 and 438 and 490 nm for BCECF). The intensity of fluorescence from the ventricular surface or from the cell was detected. [Ca]i was estimated from the following ratio: fluorescence at 505 nm during excitation at 340 nm/fluorescence at 505 nm during excitation at 380 nm. pHi was estimated from the following ratio: fluorescence at 530 nm during excitation at 490 nm/fluorescence at 530 nm during excitation at 438 nm. In the newborn, depression of contractile function during respiratory acidosis or metabolic acidosis was less than in the adult. Diastolic and systolic [Ca]i increased during respiratory acidosis in both the newborn and adult, and the net changes in [Ca]i were similar in the two age groups. During respiratory or metabolic acidosis, pHi decreased, but the decrease in the newborn was significantly less than in the adult. These data suggest that the greater resistance of the newborn myocardium to acidosis is due to the smaller change of pHi in this age group and not due to the difference in [Ca]i alteration.
Increased incidence of biliary sludge and normal gall bladder contractility in patients with high spinal cord injury
Authors: R K Tandon, R K Jain, P K Garg
Journal: Gut (1997)

Patients with spinal cord injury (SCI) have an increased prevalence of gallstones.To study prospectively the incidence of gallstones and gall bladder contractility in patients with SCI.Thirty six consecutive patients with SCI were studied: 18 patients with SCI above thoracic 10 neuronal segment (> T10) and 18 patients with SCI below T10 (< T10). An equal number each of disease controls (multiple fractures) and healthy controls were also studied. All patients and controls underwent serial ultrasonography to detect development of gallstones and ultrasonographic measurement of gall bladder contractility.A significantly higher number (9/18) of patients with SCI > T10 developed biliary sludge compared with patients with SCI < T10 (2/18), disease controls (2/18), and healthy controls (1/18) (p < 0.05). No patient developed gallstones. The gall bladder fasting volume was significantly decreased in patients with SCI > T10 (20.56 ml; 95% confidence intervals (CI) 19.74 to 21.38) compared with that in patients with SCI < T10 (27.33 ml, 95% CI 26.17 to 28.49; p < 0.05), disease controls (27.92 ml, 95% CI 26.69 to 29.15; p < 0.05), and healthy controls (28.35 ml, 95% CI 27.25 to 29.45; p < 0.05). Gall bladder contractility was normal in patients with SCI as shown by normal gall bladder residual volume and emptying time.Patients with SCI above T10 have an increased incidence of biliary sludge and a decreased gall bladder fasting volume. Gall bladder contractility is, however, normal.
<i>WWOX</i> Gene Expression Abolishes Ovarian Cancer Tumorigenicity <i>In vivo</i> and Decreases Attachment to Fibronectin via Integrin α3
Authors: Charlie Gourley, Adam J.W. Paige, Karen J. Taylor, Carol Ward, Barbara Kuske, Jieqing Zhang, Mingjun Sun, Szymon Janczar, David J. Harrison, Morwenna Muir, John F. Smyth, Hani Gabra
Journal: Cancer Research (2009)

The WW domain-containing oxidoreductase (WWOX) gene is located at FRA16D, a common fragile site involved in human cancer. Targeted deletion of Wwox in mice causes increased spontaneous tumor incidence, confirming that WWOX is a bona fide tumor suppressor gene. We show that stable transfection of WWOX into human PEO1 ovarian cancer cells, containing homozygous WWOX deletion, abolishes in vivo tumorigenicity, but this does not correlate with alteration of in vitro growth. Rather, WWOX restoration in PEO1, or WWOX overexpression in SKOV3 ovarian cancer cells, results in reduced attachment and migration on fibronectin, an extracellular matrix component linked to peritoneal metastasis. Conversely, siRNA-mediated knockdown of endogenous WWOX in A2780 ovarian cancer cells increases adhesion to fibronectin. In addition, whereas there is no WWOX-dependent difference in cell death in adherent cells, WWOX-transfected cells in suspension culture display a proapoptotic phenotype. We further show that WWOX expression reduces membranous integrin alpha(3) protein but not integrin alpha(3) mRNA levels, and that adhesion of PEO1 cells to fibronectin is predominantly mediated through integrin alpha(3). We therefore propose that WWOX acts as an ovarian tumor suppressor by modulating the interaction between tumor cells and the extracellular matrix and by inducing apoptosis in detached cells. Consistent with this, the suppression of PEO1 tumorigenicity by WWOX can be partially overcome by implanting these tumor cells in Matrigel. These data suggest a possible role for the loss of WWOX in the peritoneal dissemination of human ovarian cancer cells.
Effect of creatine on aerobic and anaerobic metabolism in skeletal muscle in swimmers.
Authors: C H Thompson, G J Kemp, A L Sanderson, R M Dixon, P Styles, D J Taylor, G K Radda
Journal: British Journal of Sports Medicine (1996)

OBJECTIVE: To examine the effect of a relatively low dose of creatine on skeletal muscle metabolism and oxygen supply in a group of training athletes. METHODS: 31P magnetic resonance and near-infrared spectroscopy were used to study calf muscle metabolism in a group of 10 female members of a university swimming team. Studies were performed before and after a six week period of training during which they took either 2 g creatine daily or placebo. Calf muscle metabolism and creatine/choline ratios were studied in resting muscle, during plantar flexion exercise (10-15 min), and during recovery from exercise. RESULTS: There was no effect of creatine on metabolite ratios at rest or on metabolism during exercise and recovery from exercise. Muscle oxygen supply and exercise performance were not improved by creatine if compared to placebo treated subjects. CONCLUSIONS: Oral creatine supplementation at 2 g daily has no effect on muscle creatine concentration, muscle oxygen supply or muscle aerobic or anaerobic metabolism during endurance exercise.
Succinate Receptors in the Kidney
Authors: Peter M.T. Deen, Joris H. Robben
Journal: Journal of the American Society of Nephrology (2011)

The G protein–coupled succinate and α-ketoglutarate receptors are closely related to the family of P2Y purinoreceptors. Although the α-ketoglutarate receptor is almost exclusively expressed in the kidney, its function is unknown. In contrast, the succinate receptor, SUCRN1, is expressed in a variety of tissues, including blood cells, adipose tissue, liver, retina, and the kidney. Recent evidence suggests SUCRN1 and its succinate ligand are novel detectors of local stress, including ischemia, hypoxia, toxicity, and hyperglycemia. Local levels of succinate in the kidney also activate the renin-angiotensin system and together with SUCRN1 may play a key role in the development of hypertension and the complications of diabetes mellitus, metabolic disease, and liver damage. This makes the succinate receptor a promising drug target to counteract an expanding number of interrelated disorders.
Genomic Drift and Evolution of Microsatellite DNAs in Human Populations
Authors: N. Takezaki, M. Nei
Journal: Molecular Biology and Evolution (2009)

In recent years, copy number variation (CNV) of DNA segments has become a hot topic in the study of genetic variation, and a large amount of CNVs has been uncovered in human populations. The CNVs involving the smallest units of DNA segments are microsatellite DNAs, and the evolutionary change of microsatellite DNAs is believed to occur mostly by the increase or decrease of one repeat unit at a time in a more or less neutral fashion. If we note that eukaryotic genomes contain millions of microsatellite loci, this pattern of nucleotide change is expected to generate random changes of genome size, that is, genomic drift, and will provide a neutral model of CNV evolution. We therefore investigated the amount of variation of the total number of repeats (TNR) per individual concerned with 145 microsatellite loci in three human populations, Africans, Europeans, and Asians. It was shown that the TNR follows the normal distribution in all three populations and that the extent of variation of TNR is more than 50% greater in Africans than in Europeans and Asians as expected from the hypothesis of African origin of modern humans. If we consider all microsatellite loci in the human genome and compute the variation of the total number of nucleotides involved (TNN), it is possible to study the contribution of microsatellite loci to the genome size variation. This study has shown that the genome sizes of human individuals are affected considerably by genomic drift of microsatellite DNA alone. This pattern of evolution is similar to that of olfactory receptor (OR) genes previously studied in human populations and support the idea that the number of OR genes has evolved in a more or less neutral fashion. However, this conclusion does not necessarily apply to the genomewide CNVs of various DNA segments, and it appears that long variant DNA fragments are deleterious and under purifying selection.
Surveillance of the Tumor Mutanome by T Cells during Progression from Primary to Recurrent Ovarian Cancer
Authors: Darin A. Wick, John R. Webb, Julie S. Nielsen, Spencer D. Martin, David R. Kroeger, Katy Milne, Mauro Castellarin, Kwame Twumasi-Boateng, Peter H. Watson, Rob A. Holt, Brad H. Nelson
Journal: Clinical Cancer Research (2013)

Cancers accumulate mutations over time, each of which brings the potential for recognition by the immune system. We evaluated T-cell recognition of the tumor mutanome in patients with ovarian cancer undergoing standard treatment.Tumor-associated T cells from 3 patients with ovarian cancer were assessed by ELISPOT for recognition of nonsynonymous mutations identified by whole exome sequencing of autologous tumor. The relative levels of mutations and responding T cells were monitored in serial tumor samples collected at primary surgery and first and second recurrence.The vast majority of mutations (78/79) were not recognized by tumor-associated T cells; however, a highly specific CD8(+) T-cell response to the mutation hydroxysteroid dehydrogenase-like protein 1 (HSDL1)(L25V) was detected in one patient. In the primary tumor, the HSDL1(L25V) mutation had low prevalence and expression, and a corresponding T-cell response was undetectable. At first recurrence, there was a striking increase in the abundance of the mutation and corresponding MHC class I epitope, and this was accompanied by the emergence of the HSDL1(L25V)-specific CD8(+) T-cell response. At second recurrence, the HSDL1(L25V) mutation and epitope continued to be expressed; however, the corresponding T-cell response was no longer detectable.The immune system can respond to the evolving ovarian cancer genome. However, the T-cell response detected here was rare, was transient, and ultimately failed to prevent disease progression. These findings reveal the limitations of spontaneous tumor immunity in the setting of standard treatments and suggest a high degree of ignorance of tumor mutations that could potentially be reversed by immunotherapy.
Vaginal birth after a caesarean is not always beneficial
Authors: Paul T-Y Ayuk
Journal: BMJ (2007)

We select the letters for these pages from the rapid responses posted on bmj.com favouring those received within five days of publication of the article to which they refer.Letters are thus an early selection of rapid responses on a particular topic.Readers should consult the website for the full list of responses and any authors' replies, which usually arrive after our selection. DeciDing on caesarean section Vaginal birth after a caesarean is not always beneficialThe study by Montgomery et al and the accompanying editorial are based on the premise that vaginal delivery after one caesarean section is necessarily a beneficial and desirable objective or outcome. 1 2 However, the box shows the risks and benefits as published in the recent RCOG (Royal College of Obstetricians and Gynaecologists) guidelines. 3 Given that most women in developed countries are unlikely to have more than two to three babies, the value of promoting vaginal delivery after one caesarean section is highly questionable.Women with a breech presentation are no longer offered a choice between vaginal delivery and caesarean section on the basis of the results of the term breech trial. 4 Must we wait for such a trial to recognise that vaginal delivery after one caesarean section costs lives and caesarean section saves lives?Women should have a choice, but this should not come before safety.To promote a process that is known to be associated with greater mortality and morbidity, or consider such a process as beneficial or desirable seems inappropriate irrespective of the reduction in women's anxiety.
Mortality Risk of Mirtazapine
Authors: Robert H. Howland
Journal: JAMA Psychiatry (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 Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Psychiatry journal
Fitness levels of middle aged martial art practitioners * Commentary
Authors: P Douris, A Chinan, M Gomez, A Aw, D Steffens, S Weiss
Journal: British Journal of Sports Medicine (2004)

To quantify and compare fitness levels of middle aged practitioners of soo bahk do (SBD; a Korean martial art similar to karate) with those of sedentary subjects.Eighteen volunteers, 14 men and four women (aged 40-60 years), participated. Nine sedentary subjects (mean age 46.7 years) and nine SBD practitioners (mean age 46.8 years) were matched for sex and age. All subjects participated in a one day battery of fitness tests. The following dependent variables were tested: body composition, balance, flexibility, quadriceps strength, grip strength, muscle endurance, and aerobic capacity.All dependent variables were analysed using paired t tests. Body composition (% body fat) for the SBD group was 18.9% v 30.8% for the sedentary group (p = 0.004). The SBD group was able to balance for 61.8 seconds v 26.2 seconds for the sedentary group (p = 0.02). The result for the sit and reach flexibility test was 22.3 cm for the SBD group v 10.4 cm for the sedentary group (p = 0.01). The number of push ups performed in one minute was 47.0 for the SBD group v 18.6 for the sedentary group (p = 0.0003), and the number of sit ups performed was 66.1 for the SBD group and 37.3 for the sedentary group (p = 0.00006). Aerobic capacity was 41.0 ml/kg/min v 31.1 ml/kg/min for the sedentary group (p = 0.04). Quadriceps strength was 99.5% (peak torque/body weight) v 83.0% for the sedentary group (p = 0.02). Only grip strength was not significantly different.There were significant differences between the groups for most of the physical fitness tests. The SBD practitioners displayed greater aerobic capacity, balance, flexibility, muscle endurance, and strength, and less body fat than the sedentary controls matched for age and sex. SBD can be considered an excellent form of exercise for the promotion of fitness in adults. Health professionals should be aware that there are alternative methods to traditional exercise that can increase the physical fitness and health of the middle aged population.
Pyrophosphorolysis-Activated Polymerization Detects Circulating Tumor DNA in Metastatic Uveal Melanoma
Authors: Jordan Madic, Sophie Piperno-Neumann, Vincent Servois, Aurore Rampanou, Maud Milder, Bénédicte Trouiller, David Gentien, Stéphanie Saada, Franck Assayag, Aurélie Thuleau, Fariba Nemati, Didier Decaudin, François-Clément Bidard, Laurence Desjardins, Pascale Mariani, Olivier Lantz, Marc-Henri Stern
Journal: Clinical Cancer Research (2012)

Abstract Purpose: To develop a molecular tool to detect circulating tumor–derived DNA (ctDNA) in the plasma from patients with uveal melanoma as a marker of tumor burden and monitor treatment efficacy. Experimental Design: A real-time PCR was developed on the basis of bidirectional pyrophosphorolysis-activated polymerization (bi-PAP) for the quantification of ctDNA using 3′blocked primer pairs specific for the 3 recurrent mutually exclusive mutations of Gα subunits GNAQ and GNA11. Results: Sensitivity and specificity of bi-PAP were assessed on serial dilutions of tumor DNA in normal DNA for the 3 recurrent mutations. Each assay could detect a single mutated molecule per reaction, whereas 104 copies of normal DNA were not detected. The ctDNA was readily detected in plasma of mice bearing uveal melanoma xenografts in amounts proportional to circulating human DNA. Finally, plasma was almost always found positive (20 of 21 tested patients) in a prospective analysis of patients with metastatic uveal melanoma. Conclusions: Bi-PAP assays detect and quantify ctDNA in patients with metastatic uveal melanoma. A prospective study is ongoing to assess the clinical usefulness of ctDNA level in uveal melanoma. Clin Cancer Res; 18(14); 3934–41. ©2012 AACR.