tbuckley/cabot-search huggingface dataset:
Association between Gc genotype and susceptibility to TB is dependent on vitamin D status
Authors: A. R. Martineau, A. C. C. S. Leandro, S. T. Anderson, S. M. Newton, K. A. Wilkinson, M. P. Nicol, S. M. Pienaar, K. H. Skolimowska, M. A. Rocha, V. C. Rolla, M. Levin, R. N. Davidson, S. A. Bremner, C. J. Griffiths, B. S. Eley, M. G. Bonecini-Almeida, R. J. Wilkinson
Journal: European Respiratory Journal (2009)

Group-specific component (Gc) variants of vitamin D binding protein differ in their affinity for vitamin D metabolites that modulate antimycobacterial immunity. We conducted studies to determine whether Gc genotype associates with susceptibility to tuberculosis (TB). The following subjects were recruited into case–control studies: in the UK, 123 adult TB patients and 140 controls, all of Gujarati Asian ethnic origin; in Brazil, 130 adult TB patients and 78 controls; and in South Africa, 281 children with TB and 182 controls. Gc genotypes were determined and their frequency was compared between cases <i>versus</i> controls. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were obtained retrospectively for 139 Gujarati Asians, and case-control analysis was stratified by vitamin D status. Interferon (IFN)-γ release assays were also performed on 36 Gujarati Asian TB contacts. The Gc2/2 genotype was strongly associated with susceptibility to active TB in Gujarati Asians, compared with Gc1/1 genotype (OR 2.81, 95% CI 1.19–6.66; p = 0.009). This association was preserved if serum 25(OH)D was &lt;20 nmol·L<sup>−1</sup> (p = 0.01) but not if serum 25(OH)D was ≥20 nmol·L<sup>−1</sup> (p = 0.36). Carriage of the Gc2 allele was associated with increased PPD of tuberculin-stimulated IFN-γ release in Gujarati Asian TB contacts (p = 0.02). No association between Gc genotype and susceptibility to TB was observed in other ethnic groups studied.
Simultaneous Bennett's fracture and metacarpophalangeal dislocation of the same thumb in a soccer player
Authors: S Jari, M Waseem, M S Srinivasan
Journal: British Journal of Sports Medicine (2000)

Double dislocations of finger joints are rare. An unusual case of a simultaneous Bennett's fracture/dislocation of the carpometacarpal joint and a dorsal dislocation of the metacarpophalangeal joint of the same thumb, and the management of this injury are reported. The patient had an excellent functional result.
36 ANALYSIS OF FACTORS ASSOCIATED WITH EARLY POSTOPERATIVE EXPRESSION OF INTERFERON- INDUCIBLE GENES IN LIVER ALLOGRAFTS
Authors: M. Burlone, P. Giarda, R. Minisini, P. Toniutto, G. Grossi, G. Occhino, E. Falleti, C. Fabris, M. Pirisi
Journal: Journal of Hepatology (2009)
CpG island density and its correlations with genomic features in mammalian genomes
Authors: Leng Han, Bing Su, Wen-Hsiung Li, Zhongming Zhao
Journal: Genome biology (2008)

Abstract Background CpG islands, which are clusters of CpG dinucleotides in GC-rich regions, are considered gene markers and represent an important feature of mammalian genomes. Previous studies of CpG islands have largely been on specific loci or within one genome. To date, there seems to be no comparative analysis of CpG islands and their density at the DNA sequence level among mammalian genomes and of their correlations with other genome features. Results In this study, we performed a systematic analysis of CpG islands in ten mammalian genomes. We found that both the number of CpG islands and their density vary greatly among genomes, though many of these genomes encode similar numbers of genes. We observed significant correlations between CpG island density and genomic features such as number of chromosomes, chromosome size, and recombination rate. We also observed a trend of higher CpG island density in telomeric regions. Furthermore, we evaluated the performance of three computational algorithms for CpG island identifications. Finally, we compared our observations in mammals to other non-mammal vertebrates. Conclusion Our study revealed that CpG islands vary greatly among mammalian genomes. Some factors such as recombination rate and chromosome size might have influenced the evolution of CpG islands in the course of mammalian evolution. Our results suggest a scenario in which an increase in chromosome number increases the rate of recombination, which in turn elevates GC content to help prevent loss of CpG islands and maintain their density. These findings should be useful for studying mammalian genomes, the role of CpG islands in gene function, and molecular evolution.
Complement Component C3 Mediates Inflammatory Injury Following Focal Cerebral Ischemia
Authors: J Mocco, William J. Mack, Andrew F. Ducruet, Sergei A. Sosunov, Michael E. Sughrue, Benjamin G. Hassid, M. Nathan Nair, Ilya Laufer, Ricardo J. Komotar, M. Claire, H. Holland, David J. Pinsky, E. Sander Connolly
Journal: Circulation Research (2006)

The complement cascade has been implicated in ischemia/reperfusion injury, and recent studies have shown that complement inhibition is a promising treatment option for acute stroke. The development of clinically useful therapies has been hindered, however, by insufficient understanding of which complement subcomponents contribute to post-ischemic injury. To address this issue, we subjected mice deficient in selected complement proteins (C1q, C3, C5) to transient focal cerebral ischemia. Of the strains investigated, only C3-/- mice were protected, as demonstrated by 34% reductions in both infarct volume (P<0.01) and neurological deficit score (P<0.05). C3-deficient mice also manifested decreased granulocyte infiltration (P<0.02) and reduced oxidative stress (P<0.05). Finally, administration of a C3a-receptor antagonist resulted in commensurate neurological improvement and stroke volume reduction (P<0.05). Together, these results establish C3 activation as the key constituent in complement-related inflammatory tissue injury following stroke and suggest a C3a anaphylatoxin-mediated mechanism.
Altered actin binding with myosin mutation in hypertrophic cardiomyopathy and sudden death
Authors: Masayoshi Kato, Kenji Takazawa, Akinori Kimura, JohannC. Rüegg, Keiko Amano, Yuepang Wang, Yoshiyuki Sakaki, Teruhiko Toyo-oka
Journal: The Lancet (1995)
OP30 * DIAGNOSTIC DELAY AND SURVIVAL IN HIGH GRADE GLIOMAS - EVIDENCE OF THE "WAITING TIME PARADOX"
Authors: A. Aggarwal, N. Herz, L. Arkush, S. Short, J. Rees
Journal: Neuro-Oncology (2014)

INTRODUCTION: We present a retrospective single centre study to determine whether delays in diagnosis in high grade glioma (HGG) impact on overall survival (OS). METHOD: Consecutive patients diagnosed with HGG at The National Hospital for Neurology and Neurosurgery, a single neuroscience centre in 2011 were reviewed. Route of referral and time from initial presentation to diagnosis were analysed and correlated with OS. RESULTS: 118 patients were studied, 92 had with glioblastoma (GBM). Diagnosis of GBM in patients presenting to emergency services was quicker than through outpatients (8 days vs 26 days, p < 0.0001), but these patients had significantly worse OS (181 days vs 386 days p = 0.0075 ). CONCLUSION: Earlier diagnosis is paradoxically associated with a worse OS in GBM. An “aggressive” phenotype with rapid symptomatic deterioration and hence emergency presentation is a poor prognostic factor not influenced by more rapid treatment or earlier diagnosis.
Cell Division Patterns in Acute Myeloid Leukemia Stem-like Cells Determine Clinical Course: A Model to Predict Patient Survival
Authors: Thomas Stiehl, Natalia Baran, Anthony D. Ho, Anna Marciniak-Czochra
Journal: Cancer Research (2015)

Acute myeloid leukemia (AML) is a heterogeneous disease in which a variety of distinct genetic alterations might occur. Recent attempts to identify the leukemia stem-like cells (LSC) have also indicated heterogeneity of these cells. On the basis of mathematical modeling and computer simulations, we have provided evidence that proliferation and self-renewal rates of the LSC population have greater impact on the course of disease than proliferation and self-renewal rates of leukemia blast populations, that is, leukemia progenitor cells. The modeling approach has enabled us to estimate the LSC properties of 31 individuals with relapsed AML and to link them to patient survival. On the basis of the estimated LSC properties, the patients can be divided into two prognostic groups that differ significantly with respect to overall survival after first relapse. The results suggest that high LSC self-renewal and proliferation rates are indicators of poor prognosis. Nevertheless, high LSC self-renewal rate may partially compensate for slow LSC proliferation and vice versa. Thus, model-based interpretation of clinical data allows estimation of prognostic factors that cannot be measured directly. This may have clinical implications for designing treatment strategies.
Increased Myocardial Oxygen Consumption and Contractile State Associated with Increased Heart Rate in Dogs
Authors: ROBERT C. BOERTH, JAMES W. COVELL, PETER E. POOL, JOHN ROSS
Journal: Circulation Research (1969)

The effects of increasing the frequency of contraction on myocardial oxygen consumption per minute (MV · o 2 ) were examined in eight dogs using an isovolumic left ventricular preparation. MV · o 2 was determined at two to four levels of heart rate in each animal. Peak wall stress was maintained constant in each animal so that changes in it would not influence the effects of heart rate on oxygen consumption per beat. As heart rate was increased, there was a highly significant linear increase in MV · o 2 . Oxygen consumption per beat was shown to be a negative linear function of the reciprocal of heart rate. Thus, as heart rate increased there was a significant increase in oxygen consumption per beat; when basal oxygen consumption was subtracted from total oxygen consumption, there was a much larger increase in oxygen consumption per beat. Myocardial contractile state, defined as the maximum observed contractile element velocity at the lowest common level of wall stress, was significantly increased by increasing heart rate. The data suggest that the increased M · Vo 2 associated with augmented heart rate is secondary to augmentation of contractile state, as well as to the increase in stress development per minute.
Reducing mortality from sudden cardiac death in the community: lessons from epidemiology and clinical applications research
Authors: N Sotoodehnia
Journal: Cardiovascular Research (2001)

The reduction of mortality from sudden cardiac death (SCD) in the community remains a challenge. Clinical—epidemiologic studies have identified a range of factors that are associated with an increased risk of SCD. While of potential etiologic and prognostic importance, these factors have limited sensitivity and a low positive predictive value for SCD. On the other hand, clinical trials have suggested that a variety of interventions, including risk factor reduction, nutritional interventions, drug therapies, cardiac procedures, and new technologies, have the potential to reduce mortality from SCD. In this review, we examine what is known about the epidemiology and clinical application of interventions to reduce mortality from SCD; and, we consider the impact of both prevention and clinical interventions on mortality from SCD from a community perspective. There is mounting evidence that supports both public health and clinical efforts to prevent the occurrence of SCD. There also is evidence suggesting that new technologies, such as automated external defibrillators, have the potential to reduce case-fatality from SCD. Further progress will depend on improved methods to identify persons-at-risk, reduction of risk factors, and application of techniques — both simple and advanced — to improve survival in victims of SCD.
Excess purine degradation in exercising muscles of patients with glycogen storage disease types V and VII.
Authors: I Mineo, N Kono, T Shimizu, N Hara, Y Yamada, S Sumi, K Nonaka, S Tarui
Journal: Journal of Clinical Investigation (1985)

To investigate purine catabolism in exercising muscles of patients with muscle glycogen storage disease, we performed ischemic forearm exercise tests and quantitated metabolites appearing in cubital venous blood. Two patients with glycogen storage disease type V and three with glycogen storage disease type VII participated in this study. Basal lactate concentrations lowered in every patient with glycogen storage disease type V or type VII. Two patients with glycogen storage disease type VII, who had markedly elevated concentrations of serum uric acid (14.3 and 11.9 mg/dl, respectively), showed high basal concentrations of ammonia (118 and 79 mumol/liter, respectively; 23 +/- 4 mumol/liter in healthy controls) and of hypoxanthine (23.4 and 20.4 mumol/liter, respectively; 2.0 +/- 0.4 mumol/liter in healthy controls). Other patients showed near normal measurements of these metabolites. After forearm exercise, ammonia, inosine, and hypoxanthine levels increased greatly in every patient studied, in contrast with the lack of increase in lactate levels. The incremental area under the concentration curves for venous ammonia was 13-fold greater in the glycogen storage disease group than in controls (1,120 +/- 182 vs. 83 +/- 26 mumol X min/liter). The incremental areas of inosine and hypoxanthine were also greater in the glycogen storage disease group (29.2 +/- 7.2 vs. 0.4 +/- 0.1 and 134.6 +/- 23.1 vs. 14.9 +/- 3.2 mumol X min/liter, respectively). The incremental areas of ammonia in controls and in glycogen storage disease patients strongly correlated with those of hypoxanthine (r = 0.984, n = 11, P less than 0.005). These findings indicated that excess purine degradation occurred in the exercising muscles of patients with glycogen storage disease types V and VII, and suggested that the ATP pool in the exercising muscles may be deranged because of defective glycogenolysis or glycolysis.
The roles of binding site arrangement and combinatorial targeting in microRNA repression of gene expression
Authors: Lawrence S Hon, Zemin Zhang
Journal: Genome biology (2007)

MicroRNAs (miRNAs) are small noncoding RNAs that bind mRNA target transcripts and repress gene expression. They have been implicated in multiple diseases, such as cancer, but the mechanisms of this involvement are not well understood. Given the complexity and degree of interactions between miRNAs and target genes, understanding how miRNAs achieve their specificity is important to understanding miRNA function and identifying their role in disease.Here we report factors that influence miRNA regulation by considering the effects of both single and multiple miRNAs targeting human genes. In the case of single miRNA targeting, we developed a metric that integrates miRNA and mRNA expression data to calculate how changes in miRNA expression affect target mRNA expression. Using the metric, our global analysis shows that the repression of a given miRNA on a target mRNA is modulated by 3' untranslated region length, the number of target sites, and the distance between a pair of binding sites. Additionally, we show that some miRNAs preferentially repress transcripts with longer CTG repeats, suggesting a possible role for miRNAs in repeat expansion disorders such as myotonic dystrophy. We also examine the large class of genes targeted by multiple miRNAs and show that specific types of genes are progressively more enriched as the number of targeting miRNAs increases. Expression microarray data further show that these highly targeted genes are downregulated relative to genes targeted by few miRNAs, which suggests that highly targeted genes are tightly regulated and that their dysregulation may lead to disease. In support of this idea, cancer genes are strongly enriched among highly targeted genes.Our data show that the rules governing miRNA targeting are complex, but that understanding the mechanisms that drive such control can uncover miRNAs' role in disease. Our study suggests that the number and arrangement of miRNA recognition sites can influence the degree and specificity of miRNA-mediated gene repression.
Psychosomatic Non-Articular Rheumatism
Authors: E. P. Edmonds
Journal: Annals of the Rheumatic Diseases (1947)

It seems now to be fairly widely agreed that emotional factors are relevant to the study of rheumatism, and particularly of non-articular rheumatism or fibro- sitis.The Horder Report (1941) stated that " Worry, anxiety, mental shock, can be often recognized as promotive of rheumatic disease ".The relationship is perhaps more often expressed as a matter of differential diagnosis between muscular pains of psychoneurotic origin and what is described as " true rheu- matism ".But quite apart from psychological considerations, there is much controversy as to what constitutes " true " non-articular rheumatism. Non-articular Rheumatism in GeneralMuch of the present controversy lies broadly between the exponents of "fibrositis " as a precise clinical and pathological entity and those, more sceptical, who recognize only a vaguer collection of conditions better described as " myalgia ".The word rheumatism has the advantage of its wide recognition by doctors and patients in the description of a certain type of pain, usually with some stiffness and tenderness, of muscle and related fibrous tissue.According to a recent definition (Annotation, Brit.med.J., 1946) the word rheumatism " by derivation implies the defluxion of a morbid humour to the part-that is to say, a local tissue change".While postulating a local tissue change, however, the word is non-committal with regard to the precise nature of this change.POSSIBLE CAUSATIVE FACTORS Some of the factors generally thought to be concerned in the production of non-articular rheumatism are as follows:(a) chill from draughts, damp, or excessive sweating; (b) trauma or strain, acute, as the " crick in the neck " or chronic, as gardeners' lumbago; fatigue from excessive or unaccustomed exercise, or from postural abnormalities such as kyphosis or flat feet; (c) infection: acute, as in influenza, sandfly fever, rubella, or many other infections; or chronic, from a focal sepsis; 36 on July 24,
Proton radiotherapy for pediatric central nervous system ependymoma: clinical outcomes for 70 patients
Authors: S. M. MacDonald, R. Sethi, B. Lavally, B. Y. Yeap, K. J. Marcus, P. Caruso, M. Pulsifer, M. Huang, D. Ebb, N. J. Tarbell, T. I. Yock
Journal: Neuro-Oncology (2013)

BackgroundEpendymoma is treated with maximal surgical resection and localized radiotherapy. Minimizing unnecessary exposure to radiation is of paramount importance for young children. Proton radiotherapy (PRT) spares healthy tissues outside the target region, but reports of clinical outcomes are scarce. We report outcomes for 70 patients treated with PRT for intracranial ependymoma.
Risk of injury in elite football played on artificial turf versus natural grass: a prospective two-cohort study
Authors: J Ekstrand, T Timpka, M Hägglund
Journal: British Journal of Sports Medicine (2006)

Objective: To compare injury risk in elite football played on artificial turf compared with natural grass. Design: Prospective two-cohort study. Setting: Male European elite football leagues. Participants: 290 players from 10 elite European clubs that had installed third-generation artificial turf surfaces in 2003–4, and 202 players from the Swedish Premier League acting as a control group. Main outcome measure: Injury incidence. Results: The incidence of injury during training and match play did not differ between surfaces for the teams in the artificial turf cohort: 2.42 v 2.94 injuries/1000 training hours and 19.60 v 21.48 injuries/1000 match hours for artificial turf and grass respectively. The risk of ankle sprain was increased in matches on artificial turf compared with grass (4.83 v 2.66 injuries/1000 match hours; rate ratio 1.81, 95% confidence interval 1.00 to 3.28). No difference in injury severity was seen between surfaces. Compared with the control cohort who played home games on natural grass, teams in the artificial turf cohort had a lower injury incidence during match play (15.26 v 23.08 injuries/1000 match hours; rate ratio 0.66, 95% confidence interval 0.48 to 0.91). Conclusions: No evidence of a greater risk of injury was found when football was played on artificial turf compared with natural grass. The higher incidence of ankle sprain on artificial turf warrants further attention, although this result should be interpreted with caution as the number of ankle sprains was low.
Playing a dirty trick on airway smooth muscle: house dust mite does it again
Authors: S. Zuyderduyn, P. S. Hiemstra
Journal: European Respiratory Journal (2011)

Increased airway smooth muscle (ASM) mass is a hallmark of asthma and is thought to be the main contributor to the increased airway hyperresponsiveness seen in asthmatics [1]. This increase is related to disease severity (reviewed in [2]) and caused by hyperplasia alone or in combination with hypertrophy, depending on the generation of airways [3, 4]. Why and how ASM mass is increased is incompletely understood, but in vitro studies have shown that ASM cells isolated from asthmatics proliferate faster in culture [5]. In addition, cultured patient cells produce more chemokines and an altered array of extracellular matrix proteins compared with those of healthy individuals [6, 7]. In vitro studies have shown that upon isolation, ASM cells display contractile function, but they rapidly change phenotype ( i.e. acquire proliferative and synthetic capacity) and become noncontractile during culture under serum-rich conditions [8]. When these synthetic–proliferative cells are serum-deprived for a prolonged period of time, a small population (so-called “hypercontractile” cells) starts re-expressing contractile protein genes, such as ACTA2 (encoding α-smooth muscle actin (α-SMA)) [9]. This dedifferentiation/modulation and differentiation/maturation of ASM cells is referred to as phenotype switching or phenotypic plasticity, and although this phenomenon clearly exists in vitro , we do not know whether this plays a role in thickening of the ASM layer.

The increase in ASM proliferation in asthma is thought to be associated with decreased levels of CCAAT enhancer protein (c/EBP)α (encoded by the CEBPA gene), a crucial controller of cell cycle progression, differentiation and inflammation. The biological effects of this protein are exerted by the full-length (p42) isoform and counteracted by a shorter isoform (p30), which is formed after translation of the protein. Previously, it was shown that ASM from asthmatics has …
1122-170 Expression of tob by human coronary arteries and BMP-mediated stimulation of coronary artery endothelial cell proliferation
Authors: Jun Xu, Terence M Doherty, Di Chen, Shuang Chen, Pinky V Tripathi, Suzhen Guo, Ejaz Ahmad, Lorraine A Fitzpatrick, Tadashi Yamamoto, Prediman K Shah, Tripathi B Rajavashisth
Journal: Journal of the American College of Cardiology (2004)