tbuckley/cabot-search huggingface dataset:
Musculoskeletal pain is associated with very low levels of vitamin D in men: results from the European Male Ageing Study
Authors: J. McBeth, S. R. Pye, T. W. O'Neill, G. J. Macfarlane, A. Tajar, G. Bartfai, S. Boonen, R. Bouillon, F. Casanueva, J. D. Finn, G. Forti, A. Giwercman, T. S. Han, I. T. Huhtaniemi, K. Kula, M. E. J. Lean, N. Pendleton, M. Punab, A. J. Silman, D. Vanderschueren, F. C. W. Wu
Journal: Annals of the Rheumatic Diseases (2010)

A study was undertaken to test the hypothesis that musculoskeletal pain is associated with low vitamin D levels but the relationship is explained by physical inactivity and/or other putative confounding factors.Men aged 40-79 years completed a postal questionnaire including a pain assessment and attended a clinical assessment (lifestyle questionnaire, physical performance tests, 25-hydroxyvitamin D3 (25-(OH)D) levels from fasting blood sample). Subjects were classified according to 25-(OH)D levels as 'normal' (> or = 15 ng/ml) or 'low' (< 15 ng/ml). The relationship between pain status and 25-(OH)D levels was assessed using logistic regression. Results are expressed as ORs and 95% CIs.3075 men of mean (SD) age 60 (11) years were included in the analysis. 1262 (41.0%) subjects were pain-free, 1550 (50.4%) reported 'other pain' that did not satisfy criteria for chronic widespread pain (CWP) and 263 (8.6%) reported CWP. Compared with patients who were pain-free, those with 'other pain' and CWP had lower 25-(OH)D levels (n=239 (18.9%), n=361 (23.3) and n=67 (24.1%), respectively, p<0.05). After adjusting for age, having 'other pain' was associated with a 30% increase in the odds of having low 25-(OH)D while CWP was associated with a 50% increase. These relationships persisted after adjusting for physical activity levels. Adjusting for additional lifestyle factors (body mass index, smoking and alcohol use) and depression attenuated these relationships, although pain remained moderately associated with increased odds of 20% of having low vitamin D levels.These findings have implications at a population level for the long-term health of individuals with musculoskeletal pain.
Genetic determinants of methotrexate treatment in rheumatoid arthritis patients: a study of polymorphisms in the adenosine pathway
Authors: P. B. Grabar, S. Rojko, D. Logar, V. Dolzan
Journal: Annals of the Rheumatic Diseases (2010)

Methotrexate (MTX) is a disease-modifying antirheumatic drug (DMARD) used for the treatment of rheumatoid arthritis (RA). Genetic polymorphisms in AMP deaminase ( AMPD1 ), 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase ( ATIC ), inosine triphosphate pyrophosphorylase ( ITPA ) and methylenetetrahydrofolate dehydrogenase ( MTHFD1 ) were shown to be associated with disease activity, MTX treatment response and MTX-induced toxicity in patients with RA.1,–,6 The aim of our study was to test these associations in Slovenian patients with RA treated with MTX.

Our study included 211 patients with RA who were previously characterised.7 Among them, 98 patients were receiving MTX monotherapy, 57 co-treated with one or more DMARD and 56 discontinued MTX before enrolment owing to MTX inefficacy and/or toxicity. The 28-joint count Disease Activity Score (DAS28) …
The Effect of a Nonabsorbed Oral Antibiotic (Rifaximin) on the Symptoms of the Irritable Bowel Syndrome
Authors: Mark Pimentel, Sandy Park, James Mirocha, Sunanda V. Kane, Yuthana Kong
Journal: Annals of Internal Medicine (2006)

Background: Alterations in gut flora may be important in the pathophysiology of the irritable bowel syndrome (IBS). Objective: To determine whether the nonabsorbed antibiotic rifaximin is more effective than placebo in reducing symptoms in adults with IBS. Design: Double-blind, randomized, placebo-controlled study. Setting: 2 tertiary care medical centers. Participants: 87 patients who met Rome I criteria for IBS and were enrolled from December 2003 to March 2005. Interventions: Participants who met enrollment criteria were randomly assigned to receive 400 mg of rifaximin 3 times daily for 10 days (n = 43) or placebo (n = 44). Eighty participants completed rifaximin therapy or placebo, and follow-up data were available for at least 34 participants per study group at any time point thereafter. Measurements: A questionnaire was administered before treatment and 7 days after treatment. The primary outcome was global improvement in IBS. Patients were then asked to keep a weekly symptom diary for 10 weeks. Results: Over the 10 weeks of follow-up, rifaximin resulted in greater improvement in IBS symptoms (P = 0.020). In addition, rifaximin recipients had a lower bloating score after treatment. Limitations: The major limitations of the study were its modest sample size and short duration and that most patients were from 1 center. Conclusions: Rifaximin improves IBS symptoms for up to 10 weeks after the discontinuation of therapy.
Molecular Physiology and Pharmacology of <i>HERG</i>
Authors: Johann Kiehn, Antonio E. Lacerda, Barbara Wible, Arthur M. Brown
Journal: Circulation (1996)

Background The human ether-a-go-go–related gene ( HERG ) is one locus for the hereditary long-QT syndrome. A hypothesis is that HERG produces the repolarizing cardiac potassium current I Kr , with the consequence that mutations in HERG prolong the QT interval by reducing I Kr . The elementary properties of HERG are unknown, and as a test of the hypothesis that HERG produces I Kr , we compared their elementary properties. Methods and Results We injected HERG cRNA into Xenopus oocytes and measured currents from single channels or current variance from the noise produced by ensembles of channels recorded from macro patches. Single-channel conductance was dependent on the extracellular potassium concentration ([K] o ) . At physiological [K] o , it was 2 picosiemens (pS), and at 100 mmol/L [K] o , it was 10 pS. Openings occurred in bursts with a mean duration of 26 ms at −100 mV. Mean open time was 3.2 ms and closed times were 1.0 and 26 ms. In excised macro patches, HERG currents were blocked by the class III antiarrhythmic drug dofetilide, with an IC 50 of 35 nmol/L. Dofetilide block was slow and greatly attenuated at positive potentials at which HERG rectifies. Conclusions The microscopic physiology of HERG and I Kr is similar, consistent with HERG being an important component of I Kr . The pharmacology is also similar; dofetilide appears to primarily block activated channels and has a much lower affinity for closed and inactivated channels.
Relationship Between Maternal Fat During Pregnancy and Risks Of Allergic and Respiratory Diseases In Early Childhood: The Mothers and Children's Environmental Health Study
Authors: Ja Hyeong Kim, Eun-Hee Ha, Hye sook Park, Mina Ha, Yun-Chul Hong, Yangho Kim, Min-ho Kim, Jin-A. Jung, NamSoo Chang
Journal: Journal of Allergy and Clinical Immunology (2014)
Analysis of LMP and TAP polymorphisms by polymerase chain reaction-restriction fragment length polymorphism in rheumatoid arthritis
Authors: J Vinasco, A Fraile, A Nieto, Y Beraun, E Pareja, L Mataran, J Martin
Journal: Annals of the Rheumatic Diseases (1998)

<h3>OBJECTIVE</h3> The aim of this study was to investigate the relation between the polymorphism of large molecular weight proteasome (LMP) (LMP2-LMP7) and transporter associated with antigen processing (TAP) (TAP1-TAP2) genes and rheumatoid arthritis (RA). <h3>METHODS</h3> Sixty RA patients and 102 ethnically matched unrelated healthy subjects were typed for LMP, TAP, and disease associated HLA-DRB1 alleles by using a new strategy based on polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) with amplification created restriction sites. <h3>RESULTS</h3> The polymorphism of LMP (LMP2-LMP7) and TAP (TAP1-TAP2) genes was examined in shared epitope positive and negative RA patients and controls. No significant differences in the LMP or TAP allele frequencies were observed between the total patient and control groups or the patients and controls positive or negative for the shared epitope. <h3>CONCLUSION</h3> The data suggest that the polymorphisms of LMP and TAP genes do not have an important influence in the pathogenesis of RA, although larger studies will be needed to provide more conclusive evidence on the role of these genes in RA. A new, highly reliable strategy for typing LMP alleles is also described.
Variation in the DEPDC5 locus is associated with progression to hepatocellular carcinoma in chronic hepatitis C virus carriers
Authors: Daiki Miki, Hidenori Ochi, C Nelson Hayes, Hiromi Abe, Tadahiko Yoshima, Hiroshi Aikata, Kenji Ikeda, Hiromitsu Kumada, Joji Toyota, Takashi Morizono, Tatsuhiko Tsunoda, Michiaki Kubo, Yusuke Nakamura, Naoyuki Kamatani, Kazuaki Chayama
Journal: Nature Genetics (2011)
Effects of phosphate on vascular function under normal conditions and influence of the uraemic state
Authors: I. Six, J. Maizel, F. C. Barreto, A. Y. Rangrez, S. Dupont, M. Slama, C. Tribouilloy, G. Choukroun, J. C. Maziere, S. Bode-Boeger, J. T. Kielstein, T. B. Drueke, Z. A. Massy
Journal: Cardiovascular Research (2012)

AimsIncreased serum phosphorus levels are associated with cardiovascular disease in patients with chronic kidney disease (CKD) and in the general population. High phosphate levels may play a direct role in vascular dysfunction. We investigated here the effects of phosphate loading and of the phosphate binder sevelamer-HCl on vascular function.
Human fetal and adult chondrocytes. Effect of insulinlike growth factors I and II, insulin, and growth hormone on clonal growth.
Authors: U Vetter, J Zapf, W Heit, G Helbing, E Heinze, E R Froesch, W M Teller
Journal: Journal of Clinical Investigation (1986)

Clonal proliferation of freshly isolated human fetal chondrocytes and adult chondrocytes in response to human insulinlike growth factors I and II (IGF I, IGF II), human biosynthetic insulin, and human growth hormone (GH) was assessed. IGF I (25 ng/ml) stimulated clonal growth of fetal chondrocytes (54 +/- 12 colonies/1,000 inserted cells, mean +/- 1 SD), but IGF II (25 ng/ml) was significantly more effective (106 +/- 12 colonies/1,000 inserted cells, P less than 0.05, unstimulated control: 14 +/- 4 colonies/1,000 inserted cells). In contrast, IGF I (25 ng/ml) was more effective in adult chondrocytes (42 +/- 6 colonies/1,000 inserted cells) than IGF II (25 ng/ml) (21 +/- 6 colonies/1,000 inserted cells; P less than 0.05, unstimulated control: 6 +/- 3 colonies/1,000 inserted cells). GH and human biosynthetic insulin did not affect clonal growth of fetal or adult chondrocytes. The clonal growth pattern of IGF-stimulated fetal and adult chondrocytes was not significantly changed when chondrocytes were first grown in monolayer culture, harvested, and then inserted in the clonal culture system. However, the adult chondrocytes showed a time-dependent decrease of stimulation of clonal growth by IGF I and II. This was not true for fetal chondrocytes. The results are compatible with the concept that IGF II is a more potent stimulant of clonal growth of chondrocytes during fetal life, whereas IGF I is more effective in stimulating clonal growth of chondrocytes during postnatal life.
Adult mastocytosis: an immunophenotypic and flow-cytometric investigation
Authors: A.D. ORMEROD, R. HERRIOT, R.J.L. DAVIDSON, H.F. SEWELL
Journal: British Journal of Dermatology (1990)

Skin mast cells of five patients with mastocytosis/urticaria pigmentosa and from four normal controls were immunophenotyped with a panel of 17 monoclonal antibodies; peripheral blood mononuclear cells from the patients were similarly labelled and analysed by flow cytometry. Cutaneous mast cells expressed leucocyte common antigen and markers of macrophage/monocyte lineage suggesting a common progenitor in the ontogeny of the two cell types. The mast cells from the patients differed from the controls, expressing HLA-DR in four cases, and this may be a feature of proliferating cells. The patients' peripheral blood T lymphocytes showed a marked increase in the activation markers HLA-DR and CD25 suggesting a contributory role, possibly via cytokines, in driving mast-cell proliferation.
Mucosal immunisation of African green monkeys ( Cercopithecus aethiops) with an attenuated parainfluenza virus expressing the SARS coronavirus spike protein for the prevention of SARS
Authors: Alexander Bukreyev, Elaine W Lamirande, Ursula J Buchholz, Leatrice N Vogel, William R Elkins, Marisa St Claire, Brian R Murphy, Kanta Subbarao, Peter L Collins
Journal: The Lancet (2004)
The Stimulation of Low-Affinity, Nontolerized Clones by Heteroclitic Antigen Analogues Causes the Breaking of Tolerance Established to an Immunodominant T Cell Epitope
Authors: Rongfang Wang, Yiran Wang-Zhu, Claudia Raja Gabaglia, Kazuhiko Kimachi, Howard M. Grey
Journal: The Journal of Experimental Medicine (1999)

H-2K mice injected, intravenously in saline or intraperitoneally in incomplete Freund's adjuvant, with large quantities of the immunodominant I-Ek–restricted epitope from moth cytochrome c (MCC) 88–103 fail to respond to subsequent immunization with this epitope when administered in complete Freund's adjuvant. This state of tolerance can be broken by immunization with certain MCC 88–103 analogues that are heteroclitic antigens as assessed on representative MCC 88–103 specific T cell clones. In this paper, the mechanism of breaking tolerance by heteroclitic antigens was investigated. The following observations were made: (a) T cell hybridomas derived from tolerance-broken animals required higher concentrations of MCC 88–103 to be stimulated than hybridomas derived from normal immune animals, suggesting that they have T cell receptors (TCRs) of lower affinity; (b) in contrast to normal immune animals whose MCC-specific TCRs are typically Vβ3+/Vα11+, none of the hybridomas derived from tolerance-broken animals expressed Vβ3, although they were all Vα11+. Also, the Vβ complementarity determining region 3 (CDR3) regions from the tolerance-broken animals did not contain the canonical structure and length characteristics of the normal MCC 88–103 immune repertoire; and (c) adoptive transfer and tolerization of MCC-specific Vβ3+/Vα11+ transgenic T cells followed by immunization with heteroclitic antigen failed to terminate the state of tolerance. Collectively, these data strongly suggest that the mechanism involved in breaking tolerance in this system is the stimulation of nontolerized, low-affinity clones, rather than reversal of anergy. Further support for this mechanism was the finding that after activation, T cells apparently have a lowered threshold with respect to the affinity of interaction with antigen required for stimulation.
Epidemiology of Nontraumatic Lower-Extremity Amputation in Area 7, Madrid, Between 1989 and 1999
Authors: Alfonso L. Calle-Pascual, Nuria Garcia-Torre, Inmaculada Moraga, Jose A. Diaz, Alejandra Duran, Guillermo Moñux, Francisco J. Serrano, Pedro J. Martín-Alvarez, Aniceto Charro, Juan P. Marañes
Journal: Diabetes Care (2001)

Diabetes remains the main cause of lower-extremity amputations (LEAs) (1,2,3). Recently (3), the number of LEAs carried out worldwide has been estimated to be >162 × 106 each year, with a high economic and social cost. More than 50% of these LEAs are performed in subjects with diabetes. Differences in the incidence of LEAs could reflect variations in risk factors, diabetes prevalence, health care systems, and lifestyle, as well as differences in population age-structure, the sources from which the case was identified, the levels of ascertainment, and the definitions of LEAs and the distinctions between major and minor LEAs. Recently, a standard approach to data collection has been described (4,5), and the first article (3) about the epidemiology of LEAs in several countries has been published. In this study, area 7 from Madrid presents the lowest LEA rates. The purpose of this article is to compare the incidence of LEAs in diabetic and nondiabetic subjects—in relation to the provision of improved foot-care after the St. Vincent Declaration—by use of a standardized approach, in the area 7 of Madrid between 1989 and 1993, between 1994 and 1996, and between 1997 and 1999.

The National Health Service has divided Madrid into 13 health care areas. The public health care system is serving >99% of the total population from the area 7 and is provided by a single hospital (Hospital Clinico San Carlos) with a single specialized service for vascular patients. According to the census in 1991, the total population for the catchment area was 569,307 (261,529 men and 307,778 women). The population with diabetes was calculated according to the Lejona study (6). In this study, the prevalence of diabetes was estimated by a randomized sample stratified by 5-year age-groups and sex. The data of this …
Dysfunctional breathing in children with asthma: a rare but relevant comorbidity
Authors: Eric P. de Groot, Eric J. Duiverman, Paul L.P. Brand
Journal: European Respiratory Journal (2012)

Hyperventilation and other clinical manifestations of dysfunctional breathing have been reported in childhood, but the prevalence is unknown. In adults, dysfunctional breathing may be a relevant comorbidity in asthma. We aimed to determine the prevalence of dysfunctional breathing in children with asthma and its impact on asthma control. We performed a cross-sectional survey in 203 asthmatic children (aged 5–18 years), using the Nijmegen Questionnaire and the paediatric Asthma Control Questionnaire. Dysfunctional breathing was found in 11 (5.3%) children; more females (eight (12.9%) out of 62) than males (three (2.1%) out 144, p=0.002). There was a dose–dependent relationship between increasing Nijmegen Questionnaire scores (increased risk of dysfunctional breathing) and poorer asthma control. Poor asthma control was more common in patients with dysfunctional breathing (10 (90.9%) out of 11 children) than in children without (65 (32.3%) out of 192 children; OR 19.3, 95% CI 3.14–430.70; p&lt;0.0001). The median Asthma Control Questionnaire in children with dysfunctional breathing was higher (median (range) 2.00 (1.50–3.17)) than in children without (0.50 (0.17–1.17); p&lt;0.001). The prevalence of dysfunctional breathing in children and adolescents referred to a hospital-based paediatric asthma clinic for severe or difficult-to-control asthma is 5%. The association between dysfunctional breathing and asthma control suggests that this may be a clinically relevant comorbidity in paediatric asthma.
Wnt/β-Catenin Signaling Promotes Podocyte Dysfunction and Albuminuria
Authors: Chunsun Dai, Donna B. Stolz, Lawrence P. Kiss, Satdarshan P. Monga, Lawrence B. Holzman, Youhua Liu
Journal: Journal of the American Society of Nephrology (2009)

Podocyte dysfunction, one of the major causes of proteinuria, leads to glomerulosclerosis and end stage renal disease, but its underlying mechanism remains poorly understood. Here we show that Wnt/beta-catenin signaling plays a critical role in podocyte injury and proteinuria. Treatment with adriamycin induced Wnt and activated beta-catenin in mouse podocytes. Overexpression of Wnt1 in vivo activated glomerular beta-catenin and aggravated albuminuria and adriamycin-induced suppression of nephrin expression, whereas blockade of Wnt signaling with Dickkopf-1 ameliorated podocyte lesions. Podocyte-specific knockout of beta-catenin protected against development of albuminuria after injury. Moreover, pharmacologic activation of beta-catenin induced albuminuria in wild-type mice but not in beta-catenin-knockout littermates. In human proteinuric kidney diseases such as diabetic nephropathy and focal segmental glomerulosclerosis, we observed upregulation of Wnt1 and active beta-catenin in podocytes. Ectopic expression of either Wnt1 or stabilized beta-catenin in vitro induced the transcription factor Snail and suppressed nephrin expression, leading to podocyte dysfunction. These results suggest that targeting hyperactive Wnt/beta-catenin signaling may represent a novel therapeutic strategy for proteinuric kidney diseases.
Quantifying similarity between motifs
Authors: Shobhit Gupta, John A Stamatoyannopoulos, Timothy L Bailey, William Noble
Journal: Genome biology (2007)

A common question within the context of de novo motif discovery is whether a newly discovered, putative motif resembles any previously discovered motif in an existing database. To answer this question, we define a statistical measure of motif-motif similarity, and we describe an algorithm, called Tomtom, for searching a database of motifs with a given query motif. Experimental simulations demonstrate the accuracy of Tomtom's E values and its effectiveness in finding similar motifs.
Rates and Determinants of Coronary and Abdominal Aortic Artery Calcium Progression in the Veterans Affairs Diabetes Trial (VADT)
Authors: Aramesh Saremi, Thomas E. Moritz, Robert J. Anderson, Carlos Abraira, William C. Duckworth, Peter D. Reaven
Journal: Diabetes Care (2010)

OBJECTIVE To determine the predictors of progression of calcified atherosclerosis and the effect of intensive glycemic control on this process in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS As part of the Risk Factors, Atherosclerosis, and Clinical Events in Diabetes (RACED) substudy of the Veterans Affairs Diabetes Trial (VADT), 197 and 189 individuals with type 2 diabetes received baseline and follow-up computed tomographic scans for measurement of coronary and abdominal artery calcium, respectively. Standard and novel risk factors were assessed at baseline, and progression of calcified atherosclerosis was determined by several methods. Progression was defined both as a categorical (square root increase of volumetric scores ≥2.5 mm3) and continuous variable. In addition, annualized percent change of volume scores was determined. RESULTS After an average follow-up of 4.6 years, &amp;gt;75% of individuals demonstrated coronary (CAC) and abdominal artery calcification (AAC) progression. Progression increased with higher baseline calcium categories but was not influenced by standard risk factors. However, the albumin-to-creatinine ratio (ACR) (P = 0.02) and lipoprotein-associated phospholipase A2 (Lp-PLA2) (P = 0.01) predicted progression of CAC, and these results were not altered by adjustment for age and other traditional risk factors. Treatment assignment (intensive versus standard) within the VADT did not influence CAC or AAC progression, irrespective of baseline calcium category. CONCLUSIONS In patients with long-standing type 2 diabetes, baseline CAC, Lp-PLA2, and ACR predicted progression of CAC. Intensive glycemic control during the VADT did not reduce progression of calcified atherosclerosis.