tbuckley/cabot-search huggingface dataset:
Growth hormone 1 (GH1) gene and performance and post-race rectal temperature during the South African Ironman triathlon * Commentary
Authors: B Walpole, T D Noakes, M Collins
Journal: British Journal of Sports Medicine (2006)

Some studies have suggested that the insertion allele of the ACE gene is associated with endurance performance, including the Ironman triathlon. It is possible that this association is due to genetic linkage between the ACE I/D locus and the T/A variant in intron 4 of the neighbouring GH1 gene. The A variant is associated with lower levels of growth hormone production. Growth hormone has multiple effects, especially on metabolism during exercise and recovery from exercise. Its production during exercise has also been shown to stimulate sweat rate and heat loss.To determine whether the GH1 gene is associated with the performance and/or post-race rectal temperatures of competitors in the South African Ironman triathlon.A total of 169 of the fastest finishing white male triathletes who completed the 2000 and/or 2001 South African Ironman triathlon and 155 control subjects were genotyped for the T/A variant in the GH1 gene. Post-race rectal temperature was also determined in 103 of these triathletes.There was no significant difference in the frequency of this polymorphism in the GH1 gene when the fastest finishing triathletes were compared with the control subjects. Post-race rectal temperatures were, however, significantly higher in those triathletes with an AA genotype (mean (SD) 37.7 (0.8) degrees C) compared with those with a TT genotype (37.2 (0.8) degrees C) (p = 0.019).The T/A polymorphism in intron 4 of the GH1 gene was not associated with performance of the fastest finishers of the South African Ironman triathlon. Post-race rectal temperatures were, however, significantly higher in the fastest finishing athletes, who were homozygous for a GH1 genotype associated with lower growth hormone production.
Gleaning relapse risk from B cell phenotype: decreased CD5<sup>+</sup>B cells portend a shorter time to relapse after B cell depletion in patients with ANCA-associated vasculitis
Authors: Donna O Bunch, Carmen E Mendoza, Lydia T Aybar, Elizabeth S Kotzen, Kerry R Colby, Yichun Hu, Susan L Hogan, Caroline J Poulton, John L Schmitz, Ronald J Falk, Patrick H Nachman, William F Pendergraft, JulieAnne G McGregor
Journal: Annals of the Rheumatic Diseases (2015)

B cell depletion is an effective remission induction and maintenance therapy in patients with antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV).1–6 Rituximab targets both pathogenic effector B cells and protective regulatory B cells. To avoid infections and adverse events from therapy, clinicians require improved markers of disease activity and impending relapse to guide immunosuppression strategies following B cell depletion. We reported that CD5+ B cells, as a surrogate marker of B regulatory cells, are decreased in patients with active AAV and normalise during disease remission.7 After B cell depletion, patients who repopulated with a low or decreasing percentage of CD5+ B cells and were on low maintenance immunosuppression had a shorter time to relapse than patients on similar levels of immunosuppression with normalised CD5+ B cells or patients with similarly low CD5+ B cells but higher immunosuppression. The CD5+CD24hiCD38hi B cell subpopulation correlates inversely with active disease but parallels both interleukin (IL)-10 production and suppression of ANCA.8 CD5 may identify B cells enriched in IL-10 production, the defining cytokine of B regulatory cells.8 ,9 Whether CD5+ B cells can serve as an indicator of time to relapse without considering remission maintenance immunosuppression dose is not known. We sought to address this question and confirm our previous findings in a larger cohort by separating patients solely based on their CD5+ B cells at repopulation.

We examined B cell phenotype in 50 patients with AAV following rituximab therapy by flow cytometry (table …
Pharmacodynamic effect of dipyridamole on thallium-201 myocardial perfusion in progressive systemic sclerosis with diffuse scleroderma.
Authors: A Kahan, J Y Devaux, B Amor, C J Menkes, S Weber, J M Foult, A Venot, F Guerin, M Degeorges, J C Roucayrol
Journal: Annals of the Rheumatic Diseases (1986)

We evaluated the effect of dipyridamole on thallium-201 myocardial perfusion in 23 patients with progressive systemic sclerosis (PSS) with diffuse scleroderma. Thallium-201 single photon emission computed tomography (SPECT) was performed at rest and after coronary artery vasodilatation with intravenous dipyridamole (0.14 mg/kg/min for four minutes). The left myocardium was divided into nine segments; each segment was graded as 2.0, 1.5, 1.0, 0.5, 0 (zero represents no activity). Dipyridamole significantly improved resting thallium-201 myocardial perfusion: the mean (SD) number of segments with thallium defects decreased from 6.0 (2.1) at rest to 4.1 (2.5) after dipyridamole (p less than 0.0001); the mean (SD) score in segments with resting defects increased from 0.92 (0.24) at rest to 1.13 (0.38) after dipyridamole (p less than 0.0001); the mean (SD) global score per patient increased from 10.2 (1.8) at rest to 11.4 (2.1) after dipyridamole (p less than 0.02); the global score increased by at least 2.0 in 12 patients and worsened by at least 2.0 in three patients only (p = 0.05). The results of this acute study suggest that some drugs with potent vasodilator activity on small coronary arteries may be beneficial in the treatment of PSS patients with thallium-201 myocardial perfusion abnormalities.
Psychological Stress: A Social Pollutant That May Enhance Environmental Risk
Authors: Rosalind J. Wright
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

the study period.Nonetheless, taken together, these two studies provide compelling evidence that CT scan scores are good predictors of future lung dysfunction.It would have been interesting to know if higher baseline CT scores were predictive of an accelerated rate of FEV 1 decline from baseline to follow-up spirometry using longitudinal modeling; however, this study may not have been powered to evaluate this highly variable outcome.It is important to realize that further studies will be needed to determine whether or not specific findings in chest radiographs or CT scans will be able to directly predict outcomes in a given patient.Overall this study is novel in its confirmation for the CF community that CT scans and plain chest radiographs have a role in predicting future lung disease and may be useful in identifying children at risk for worse pulmonary outcomes.The optimal timing of scored radiography to predict outcomes is unknown.The average age at baseline chest radiograph and CT scan was 11.5 years in Sanders' observation, and generally the radiography scores, both on CT scan and on chest radiograph, showed mild structural lung disease.Earlier imaging might allow earlier intervention for children at risk ( 2), but could be too early to pick up the magnitude of structural change seen in this study.More research is needed and the Cystic Fibrosis Foundation's registry (1) could be an important tool for correlating radiology with future lung dysfunction in a large cohort.CFF guidelines currently recommend obtaining yearly chest radiographs (14, 15).However, these radiographs need to be scored by trained radiologists using standardized scoring systems (5, 13) to be of greatest use in epidemiologic analyses.If standardized scores were reported with yearly CF patient data to the registry in a more consistent manner, then comprehensive longitudinal analyses could be accomplished.Chest CT scans may have a role the routine monitoring of children with CF; however, radiation exposure must be minimized, particularly if repeated scans are to be obtained over the life span.More importantly, it appears that plain chest radiographs with rigorously applied scoring systems may be as effective in predicting lung disease progression and would accomplish this goal with less radiation exposure and at lower cost.
Octreotide Versus Octreotide Plus Interferon-Alpha in Endocrine Gastroenteropancreatic Tumors: A Randomized Trial
Authors: Rudolf Arnold, Anja Rinke, Klaus-Jochen Klose, Hans-Helge Müller, Matthias Wied, Karin Zamzow, Christina Schmidt, Carmen Schade-Brittinger, Peter Barth, Roland Moll
Journal: Clinical Gastroenterology and Hepatology (2005)
Vaccinia virus protein A46R targets multiple Toll-like–interleukin-1 receptor adaptors and contributes to virulence
Authors: Julianne Stack, Ismar R. Haga, Martina Schröder, Nathan W. Bartlett, Geraldine Maloney, Patrick C. Reading, Katherine A. Fitzgerald, Geoffrey L. Smith, Andrew G. Bowie
Journal: The Journal of Experimental Medicine (2005)

Viral immune evasion strategies target key aspects of the host antiviral response. Recently, it has been recognized that Toll-like receptors (TLRs) have a role in innate defense against viruses. Here, we define the function of the vaccinia virus (VV) protein A46R and show it inhibits intracellular signalling by a range of TLRs. TLR signalling is triggered by homotypic interactions between the Toll-like-interleukin-1 resistance (TIR) domains of the receptors and adaptor molecules. A46R contains a TIR domain and is the only viral TIR domain-containing protein identified to date. We demonstrate that A46R targets the host TIR adaptors myeloid differentiation factor 88 (MyD88), MyD88 adaptor-like, TIR domain-containing adaptor inducing IFN-beta (TRIF), and the TRIF-related adaptor molecule and thereby interferes with downstream activation of mitogen-activated protein kinases and nuclear factor kappaB. TRIF mediates activation of interferon (IFN) regulatory factor 3 (IRF3) and induction of IFN-beta by TLR3 and TLR4 and suppresses VV replication in macrophages. Here, A46R disrupted TRIF-induced IRF3 activation and induction of the TRIF-dependent gene regulated on activation, normal T cell expressed and secreted. Furthermore, we show that A46R is functionally distinct from another described VV TLR inhibitor, A52R. Importantly, VV lacking the A46R gene was attenuated in a murine intranasal model, demonstrating the importance of A46R for VV virulence.
ANALYSIS OF SPOKEN LANGUAGE OF PATIENTS WITH AFFECTIVE DISORDERS
Authors: Stanley Newman, Vera G. Mather
Journal: American Journal of Psychiatry (1938)

Clinical descriptions and language analyses are presented of four patients with affective disorders. The characteristics of speech are discussed which were most consistently observed in each syndrome as based on a study of 40 patients of which the four described in detail are representative. The observations are outlined in the following table: One atypical case, presenting a mixed state of the manic-depressive group, is described in which pressure of activity and speech was associated with depression, apprehension, bewilderment and self-accusations. Speech analysis showed vigorous articulatory movements; wide pitch range; gliding pitch changes associated with accents; fast speech tempo; infrequent, prosodic pauses; pharyngeal resonance; absence of glottal rasping; colloquial level of style; extreme and frequent degree concepts; rich syntactic elaboration with diversified syntactic techniques; quick initiation of responses; lengthy responses dealing with single theme but disordered in sequence.
Therapeutic Inhibition of miR-208a Improves Cardiac Function and Survival During Heart Failure
Authors: Rusty L. Montgomery, Thomas G. Hullinger, Hillary M. Semus, Brent A. Dickinson, Anita G. Seto, Joshua M. Lynch, Christianna Stack, Paul A. Latimer, Eric N. Olson, Eva van Rooij
Journal: Circulation (2011)

Diastolic dysfunction in response to hypertrophy is a major clinical syndrome with few therapeutic options. MicroRNAs act as negative regulators of gene expression by inhibiting translation or promoting degradation of target mRNAs. Previously, we reported that genetic deletion of the cardiac-specific miR-208a prevents pathological cardiac remodeling and upregulation of Myh7 in response to pressure overload. Whether this miRNA might contribute to diastolic dysfunction or other forms of heart disease is currently unknown.Here, we show that systemic delivery of an antisense oligonucleotide induces potent and sustained silencing of miR-208a in the heart. Therapeutic inhibition of miR-208a by subcutaneous delivery of antimiR-208a during hypertension-induced heart failure in Dahl hypertensive rats dose-dependently prevents pathological myosin switching and cardiac remodeling while improving cardiac function, overall health, and survival. Transcriptional profiling indicates that antimiR-208a evokes prominent effects on cardiac gene expression; plasma analysis indicates significant changes in circulating levels of miRNAs on antimiR-208a treatment.These studies indicate the potential of oligonucleotide-based therapies for modulating cardiac miRNAs and validate miR-208 as a potent therapeutic target for the modulation of cardiac function and remodeling during heart disease progression.
Soluble RANKL and Risk of Nontraumatic Fracture
Authors: Georg Schett
Journal: JAMA (2004)

The receptor activator of nuclear factor kappaB ligand (RANKL) is essential for osteoclast and, possibly, osteoblast activation and may represent a key link between bone formation and resorption.To determine the relationship between serum level of RANKL and the risk of nontraumatic fracture.As part of a prospective population-based study conducted in Bruneck, Italy, we recorded all fractures that occurred between 1990 and 2000 in 906 participants and classified them as traumatic (n = 115) or nontraumatic (n = 31). Serum levels of RANKL and osteoprotegerin and characteristics of bone metabolism and lifestyle were assessed in 1990 and at follow-up in 1995 and 2000.Incident nontraumatic fracture by levels of RANKL.Levels of RANKL did not differ between sexes and were not related to age, menopausal status, lifestyle characteristics, or data from bone ultrasound at the heel. However, RANKL emerged as a significant predictor of nontraumatic fracture. In pooled logistic regression analysis, the relative risks of nontraumatic fracture in the lowest and middle vs highest tertile for RANKL were 10.0 (95% confidence interval [CI], 2.3-43.1) and 3.9 (95% CI, 0.8-19.0) (P<.001 for trend), respectively. Patients in the highest-tertile group had a low risk of fracture even in the presence of other predisposing factors, whereas women aged 60 years or older in the lowest tertile had a 5-year rate of nontraumatic fracture greater than 7%.A low level of RANKL is an independent predictor of nontraumatic fracture. This finding is consistent with the hypothesis of an important role of RANKL in human bone turnover and if confirmed in future investigations may gain relevance for assessment of fracture risk.
Acute Lymphoblastic Leukemia of Male-Recipient Origin Demonstrating Female Karyotype After Cord Blood Transplantation
Authors: Nobuhiko Imahashi, Haruhiko Ohashi, Kayo Arita, Kunio Kitamura, Taro Takahashi, Yukiyasu Ozawa, Koichi Miyamura
Journal: Journal of Clinical Oncology (2010)
Mucosal gene signatures to predict response to infliximab in patients with ulcerative colitis
Authors: I. Arijs, K. Li, G. Toedter, R. Quintens, L. Van Lommel, K. Van Steen, P. Leemans, G. De Hertogh, K. Lemaire, M. Ferrante, F. Schnitzler, L. Thorrez, K. Ma, X.-Y. R. Song, C. Marano, G. Van Assche, S. Vermeire, K. Geboes, F. Schuit, F. Baribaud, P. Rutgeerts
Journal: Gut (2009)

<h3>Background and aims:</h3> Infliximab is an effective treatment for ulcerative colitis with over 60% of patients responding to treatment and up to 30% reaching remission. The mechanism of resistance to anti-tumour necrosis factor α (anti-TNFα) is unknown. This study used colonic mucosal gene expression to provide a predictive response signature for infliximab treatment in ulcerative colitis. <h3>Methods:</h3> Two cohorts of patients who received their first treatment with infliximab for refractory ulcerative colitis were studied. Response to infliximab was defined as endoscopic and histological healing. Total RNA from pre-treatment colonic mucosal biopsies was analysed with Affymetrix Human Genome U133 Plus 2.0 Arrays. Quantitative RT-PCR was used to confirm microarray data. <h3>Results:</h3> For predicting response to infliximab treatment, pre-treatment colonic mucosal expression profiles were compared for responders and non-responders. Comparative analysis identified 179 differentially expressed probe sets in cohort A and 361 in cohort B with an overlap of 74 probe sets, representing 53 known genes, between both analyses. Comparative analysis of both cohorts combined, yielded 212 differentially expressed probe sets. The top five differentially expressed genes in a combined analysis of both cohorts were osteoprotegerin, stanniocalcin-1, prostaglandin-endoperoxide synthase 2, interleukin 13 receptor alpha 2 and interleukin 11. All proteins encoded by these genes are involved in the adaptive immune response. These markers separated responders from non-responders with 95% sensitivity and 85% specificity. <h3>Conclusion:</h3> Gene array studies of ulcerative colitis mucosal biopsies identified predictive panels of genes for (non-)response to infliximab. Further study of the pathways involved should allow a better understanding of the mechanisms of resistance to infliximab therapy in ulcerative colitis. <h3></h3> ClinicalTrials.gov number, NCT00639821.
High Intron Sequence Conservation Across Three Mammalian Orders Suggests Functional Constraints
Authors: M. P. Hare
Journal: Molecular Biology and Evolution (2003)

Several studies have demonstrated high levels of sequence conservation in noncoding DNA compared between two species (e.g., human and mouse), and interpreted this conservation as evidence for functional constraints. If this interpretation is correct, it suggests the existence of a hidden class of abundant regulatory elements. However, much of the noncoding sequence conserved between two species may result from chance or from small-scale heterogeneity in mutation rates. Stronger inferences are expected from sequence comparisons using more than two taxa, and by testing for spatial patterns of conservation in addition to primary sequence similarity. We used a Bayesian local alignment method to compare approximately 10 kb of intron sequence from nine genes in a pairwise manner between human, whale, and seal to test whether the degree and pattern of conservation is consistent with neutral divergence. Comparison of the three sets of conserved gapless pairwise blocks revealed the following patterns: The proportion of identical intron nucleotides averaged 47% in pairwise comparisons and 28% across the three taxa. Proportions of conserved sequence were similar in unique sequence and general mammalian repetitive elements. We simulated sequence evolution under a neutral model using published estimates of substitution rate heterogeneity for noncoding DNA and found pairwise identity at 33% and three-taxon identity at 16% of nucleotide sites. Spatial patterns of primary sequence conservation were also nonrandomly distributed within introns. Overall, segments of intron sequence closer to flanking exons were significantly more conserved than interior intron sequence. This level of intron sequence conservation is above that expected by chance and strongly suggests that intron sequences are playing a larger functional role in gene regulation than previously realized.
Neurological Manifestations of the Hyperventilation Syndrome
Authors: G D Perkin, R Joseph
Journal: Journal of the Royal Society of Medicine (1986)

Seventy-eight patients with the hyperventilation syndrome are described, none of whom had been diagnosed prior to referral for neurological assessment. There is a constellation of symptoms associated with this condition, and attacks need to be reproduced by hyperventilation in order for the diagnosis to be established. Loss of consciousness and paraesthesiae were more frequent than in previously published series.
Prenatal animal contact and gene expression of innate immunity receptors at birth are associated with atopic dermatitis
Authors: Caroline Roduit, Johanna Wohlgensinger, Remo Frei, Sondhja Bitter, Christian Bieli, Susanne Loeliger, Gisela Büchele, Josef Riedler, Jean-Charles Dalphin, Sami Remes, Marjut Roponen, Juha Pekkanen, Michael Kabesch, Bianca Schaub, Erika von Mutius, Charlotte Braun-Fahrländer, Roger Lauener
Journal: Journal of Allergy and Clinical Immunology (2010)
Endothelial cell-mediated conversion of Glu-plasminogen to Lys-plasminogen. Further evidence for assembly of the fibrinolytic system on the endothelial cell surface.
Authors: K A Hajjar, R L Nachman
Journal: Journal of Clinical Investigation (1988)

Lysine-plasminogen (Lys-PLG), the plasmin-modified form of native glutamic acid-plasminogen (Glu-PLG), displays enhanced binding affinity for fibrin and also enhanced activation by urokinase and tissue plasminogen activator. We previously demonstrated high-affinity, specific, and functional binding of Glu-PLG as well as tissue plasminogen activator to cultured human umbilical vein endothelial cells (HUVEC). In the present study, we demonstrate binding of Lys-PLG to HUVEC, as well as conversion of Glu-PLG to Lys-PLG at the cell surface. Binding of Lys-PLG to HUVEC was saturable, reversible, epsilon-aminocaproic acid-sensitive, and involved two saturable sites with Kd's of 142 pM and 120 nM, respectively. Upon incubation with Glu-PLG, HUVEC, as well as endothelium in situ, partially converted the ligand to a Lys-PLG-like species. Conversion by HUVEC was blocked by diisopropyl-fluorophosphate, but not by other serine protease inhibitors, including alpha 2-plasmin inhibitor. Eluates of intact umbilical cord vessels contained Lys-PLG by immunoblot analysis. Lys-PLG was also identified immunohistochemically on the endothelial surface of vessels from a variety of normal and inflamed tissues. Thus, endothelial cells appear to actively modify circulating Glu-PLG, bind Lys-PLG to their surface, and thus enhance the fibrinolytic potential of the blood vessel wall.
Occult alveolar haemorrhage in pulmonary veno-occlusive disease
Authors: A. Rabiller
Journal: European Respiratory Journal (2005)

Pulmonary veno-occlusive disease (PVOD) is a rare cause of pulmonary arterial hypertension that affects predominantly post-capillary pulmonary vessels. A major concern with PVOD is the poor response to available therapies and the risk of pulmonary oedema with continuous intravenous epoprostenol. The present authors hypothesised that alveolar haemorrhage may be a characteristic feature of pulmonary veno-occlusive disease, as compared with other forms of pulmonary arterial hypertension that predominantly involve pre-capillary pulmonary arteries. This paper reports a series of 19 patients with either PVOD (n = 8) or idiopathic pulmonary arterial hypertension (IPAH; n = 11) who underwent bronchoalveolar lavage. Cytological analyses were performed and differential counts were made on Perls-stained preparations. The Golde score was used to assess alveolar haemorrhage. As compared with IPAH, PVOD was characterised by a higher percentage of haemosiderin-laden macrophages (40+/-37 versus 3+/-6%), resulting in elevated Golde scores (81+/-88 versus 4+/-10). It was concluded that occult alveolar haemorrhage is a common feature of pulmonary veno-occlusive disease. Detecting occult alveolar haemorrhage may be of interest in the diagnostic approach of pulmonary veno-occlusive disease.