tbuckley/cabot-search huggingface dataset:
Selective proteasome inhibitors may provide a novel therapeutic approach to Mycobacterium tuberculosis
Authors: S Mahendran
Journal: Thorax (2010)

<h3>Aims</h3> To examine the cardiac structure and function of Arabic athletes and to establish if the European Society of Cardiology (ESC) guidelines for the interpretation of an athlete9s ECG are applicable to this ethnicity. <h3>Methods</h3> 600 high-level Arabic, 415 Black African, 160 Caucasian male athletes (exercising ≥6 h/week) and 201 Arabic controls presented for ECG and echocardiographic screening. <h3>Results</h3> 9 athletes (0.7%) were identified with a cardiac pathology associated with sudden cardiac death. Two Arabics (0.3%) and five Black Africans (1.2%) were diagnosed with hypertrophic cardiomyopathy; a prevalence four times greater in Black African compared to Arabic athletes. Arabic athletes had significantly greater (p&lt;0.05) left ventricular (LV) end-diastolic diameters, maximal LV wall thicknesses and LV mass compared with controls; yet were significantly smaller than Black African and Caucasian athletes. The percentage of athletes demonstrating LV hypertrophy (≥12 mm) was comparable between Arabic, Black African and Caucasian populations (0.5%, 0.5% and 0.6%, respectively). There was no difference in the frequency of an uncommon and training-unrelated ECG between Arabic and Caucasian. However, Black Africans demonstrated a significantly greater prevalence than Arabic and Caucasian athletes (20% vs 8.4% and 6.9%, p&lt;0.001); specifically more right/left atrial enlargement and T wave inversion. <h3>Conclusions</h3> Arabic athletes present significantly smaller cardiac dimensions than Black African and Caucasian athletes. There was no significant difference between the frequency of an uncommon and training-unrelated ECG between Arabic and Caucasian athletes. Therefore, the use of ESC guidelines for the interpretation of an athlete9s ECG is clinically relevant and acceptable for use within Arabic athletes.
Phosphoprotein of Human Parainfluenza Virus Type 3 Blocks Autophagosome-Lysosome Fusion to Increase Virus Production
Authors: Binbin Ding, Guangyuan Zhang, Xiaodan Yang, Shengwei Zhang, Longyun Chen, Qin Yan, Mengyao Xu, Amiya K. Banerjee, Mingzhou Chen
Journal: Cell Host & Microbe (2014)
(13-15) Juvenile dermatomyositis
Authors: E.B.D. Hamilton
Journal: British Journal of Dermatology (2006)

Journal Article (13–15) Juvenile dermatomyositis Get access E.B.D. Hamilton E.B.D. Hamilton Department of Rheumatology, King's College Hospital Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 95, Issue s14, 1 December 1976, Pages 41–43, https://doi.org/10.1111/j.1365-2133.1976.tb07905.x Published: 01 December 1976
Ulcerative colitis with ankylosing spondylitis.
Authors: M I Jayson, I A Bouchier
Journal: Annals of the Rheumatic Diseases (1968)

Although ankylosing spondylitis and ulcerative colitis are uncommon diseases, there appears to be an association between them.Wright and Watkinson (1965) examined 234 patients with ulcerative colitis and the same number of controls; 42 (17 9 per cent.) of their ulcerative colitic patients showed radio- logical "moderate" or "severe" sacro-iliitis, with typical ankylosing spondylitis in nine (3 -8 per cent.).Only eleven (4 7 per cent.) of the controls had sacro-iliitis.Conversely, among the 399 patients with ankylosing spondylitis attending the London Hospital, Steinberg and Storey (1957) found four cases (1 per cent.) of clinical ulcerative colitis, and Romanus (1953), Wilkinson and Bywaters (1958), McBride, King, Baikie, Crean, and Sircus (1963), and Serre and Simon (1964) have reported this incidence as being up to 3 9 per cent.Ulcerative colitis is a disease of unknown aetiology in which there is inflammation of the large bowel.The diagnosis may be made from the clinical symp- toms, sigmoidoscopic appearances, rectal biopsy, and barium enema examination.It is recognized that patients may be symptom-free and yet demon- strate the changes of ulcerative colitis on investigation (Dick, Holt, and Dalton, 1966; Kiefer and Gialanella, 1960).Furthermore, there may be little correlation between x-ray and sigmoidoscopic appearances, the enema showing typical changes and the sigmoidoscopy being virtually normal and vice versa (Edling, Eklof, Kistner, and Lagerlof, 1966, Sparberg, Fennessy, and Kirsner, 1966).In at- tempting to determine the prevalence of ulcerative colitis in patients with ankylosing spondylitis, it is therefore necessary to perform both sigmoidoscopic and barium enema examinations in all cases.
Liver function from Y to Z
Authors: Irwin M. Arias
Journal: Journal of Clinical Investigation (2012)

In the 1960s, my lab was interested in understanding how bilirubin and other organic anions are transferred from the plasma through the liver cell and into the bile. We performed gel filtration of liver supernatants and identified two protein fractions, designated Y and Z, which bound organic anions including bilirubin, and thus we proposed that they were involved in hepatic uptake of organic anions from plasma. Subsequently, the Y and Z proteins responsible for this binding activity were purified, cloned, and sequenced. Y was identified as a member of the glutathione S-transferase (GST) protein family and Z found to be a member of the fatty acid–binding protein (FABP) family. These proteins have since been shown to have additional surprising roles, but understanding of their full role in physiology and disease has not yet been achieved.
Persisting zones of slow impulse conduction in developing chicken hearts.
Authors: F de Jong, T Opthof, A A Wilde, M J Janse, R Charles, W H Lamers, A F Moorman
Journal: Circulation Research (1992)

We performed a correlative electrophysiological and immunohistochemical study of embryonic chicken hearts during the septational period (Hamburger and Hamilton stages 13-31 [2-7 days of incubation]). The analyses yield conclusive evidence for slow conduction, up to 7 days of development, in the outflow tract, in the atrioventricular canal, and in the sinoatrial junction. The conduction velocity remains approximately 1 cm/sec in the outflow tract and increases in the ventricle 20-fold to approximately 20 cm/sec between 2 and 7 days of development. Transmembrane potentials of myocytes in the outflow tract and atrioventricular canal slowly rise (less than 5 V/sec), whereas in the atrium and ventricle, the upstroke velocity is eightfold to 13-fold higher. In the outflow tract, repolarization is completed only after the start of the next cycle. Because of the persistence of slow conduction, the myocardium flanking the developing atria and ventricle is thought to represent segments of persisting "primary" myocardium, whereas the more rapidly conducting "working" myocardium of the ventricle and atria is thought to represent more advanced stages of myocardial differentiation. The persisting primary myocardium was characterized by a continued coexpression of both the atrial and ventricular isoforms of myosin heavy chain. The developing atria and ventricle could be demarcated morphologically from the primary myocardium because the free walls of these segments only express their respective isoforms of myosin heavy chain. The slowly conducting myocardial zones appear to be essential for the function of the embryonic heart because 1) they provide the septating heart with alternating segments of slow and relatively fast conduction necessary for consecutive contraction of the atrial and ventricular segments and 2) their sphincterlike prolonged peristaltic contraction pattern can substitute for the adult type of one-way valves that start to develop at the end of septation.
Palliative Radiation Therapy Practice in Patients With Metastatic Non–Small-Cell Lung Cancer: A Cancer Care Outcomes Research and Surveillance Consortium (CanCORS) Study
Authors: Aileen B. Chen, Angel Cronin, Jane C. Weeks, Elizabeth A. Chrischilles, Jennifer Malin, James A. Hayman, Deborah Schrag
Journal: Journal of Clinical Oncology (2013)

Randomized data suggest that single-fraction or short-course palliative radiation therapy (RT) is sufficient in the majority of patients with metastatic cancer. We investigated population-based patterns in the use of palliative RT among patients with metastatic non-small-cell lung cancer (NSCLC).From patients diagnosed with lung cancer from 2003 to 2005 at a participating geographic or organizational site and who consented to the Cancer Care Outcomes Research and Surveillance Consortium study, we identified patients with metastatic NSCLC who had complete medical records abstractions. Patient characteristics and clinical factors associated with receipt of palliative RT and RT intensity (total dose and number of treatments) were evaluated with multivariable regression.Of 1,574 patients with metastatic NSCLC, 780 (50%) received at least one course of RT, and 21% and 12% received RT to the chest and bone, respectively. Use of palliative RT was associated with younger age at diagnosis and receipt of chemotherapy and surgery to metastatic sites. Among patients receiving palliative bone RT, only 6% received single-fraction treatment. Among patients receiving palliative chest RT, 42% received more than 20 fractions. Patients treated in integrated networks were more likely to receive lower doses and fewer fractions to the bone and chest.When palliative RT is used in patients with metastatic NSCLC, a substantial proportion of patients receive a greater number of treatments and higher doses than supported by current evidence, suggesting an opportunity to improve care delivery.
Clinical Utility of Creatinine- and Cystatin C–Based Definition of Renal Function for Risk Prediction of Primary Cardiovascular Events in Patients With Diabetes
Authors: Ben Schöttker, Christian Herder, Heiko Müller, Hermann Brenner, Dietrich Rothenbacher
Journal: Diabetes Care (2012)

To assess the cardiovascular risk of diabetic subjects with chronic kidney disease (CKD) based on different estimated glomerular filtration rate (eGFR) equations and to evaluate which definition of CKD best improves cardiovascular risk prediction of the Framingham Cardiovascular Risk Score (Framingham-CV-RS).CKD was defined as eGFR <60 mL/min/1.73 m(2), estimated by the creatinine-based Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations and a cystatin C-based equation (CKD-CysC). Cox regression was used to estimate hazard ratios (HRs) of subjects with CKD for incident cardiovascular events in a cohort of 1,153 individuals with diabetes (baseline age 50-74 years). Furthermore, the CKD definitions were added individually to a reference model comprising the Framingham-CV-RS variables and HbA(1c), and measures of model discrimination and reclassification were assessed.During 5 years of follow-up, 95 individuals had a primary cardiovascular event. Crude HRs were increased for all CKD definitions. However, after adjusting for established cardiovascular risk factors, HRs for both creatinine-based CKD definitions were attenuated to point estimates of 1.03, whereas the HRs for the cystatin C-based CKD definition remained significantly increased (HR 1.75 [95% CI 1.07-2.87]). Extension of the reference model by the different CKD definitions resulted in an increase in the c statistic only when adding CKD-CysC (from 0.638 to 0.644) along with a net reclassification improvement of 8.9%.Only the cystatin C-based CKD definition was an independent risk predictor for cardiovascular events in our diabetic study cohort and indicated a potentially better clinical utility for cardiovascular risk prediction than creatinine-based equations.
Different Regulatory Mechanisms Underlie Similar Transposable Element Profiles in Pufferfish and Fruitflies
Authors: Daniel E. Neafsey, Justin P. Blumenstiel, Daniel L. Hartl
Journal: Molecular Biology and Evolution (2004)

Comparative analysis of recently sequenced eukaryotic genomes has uncovered extensive variation in transposable element (TE) abundance, diversity, and distribution. The TE profile in the sequenced pufferfish genomes is more similar to that of Drosophila melanogaster than to human or mouse, in that pufferfish TEs exhibit low overall abundance, high family diversity, and localization in the heterochromatin. It has been suggested that selection against the deleterious effects of ectopic recombination between TEs has structured the TE profile in Drosophila and pufferfish but not in humans. We test this hypothesis by measuring the sample frequency of 48 euchromatic TE insertions in the genome of the green spotted pufferfish (Tetraodon nigroviridis). We estimate the strength of selection acting on recent insertions by analyzing the site frequency spectrum using a maximum-likelihood approach. We show that in contrast to Drosophila, euchromatic TE insertions in Tetraodon are selectively neutral and that the low copy number and compartmentalized distribution of TEs in the Tetraodon genome must be caused by regulation by means other than purifying selection acting on recent insertions. Inference of regulatory processes governing TE profiles should take into account factors such as effective population size, incidence of inbreeding/outcrossing, and other species-specific traits.
Osteoarthritis and magnetic resonance imaging: potential and problems.
Authors: C W Hutton, W Vennart
Journal: Annals of the Rheumatic Diseases (1995)

To date, MRI has primarily been used to study anatomical changes, and at a resolution that makes detailed analysis of focal change difficult. This is primarily because cost limits the development and use of tailor made research systems. The detailed analysis of soft tissue, cartilage, and bone marrow images should provide a fruitful non-invasive method to study OA. However, the development of MRI methods to study movement, diffusion and perfusion, and the spatial localisation of spectroscopic information, promises a revolution in the study of the living joint in man.
Beneficial effect of SPM-5185, a cysteine-containing nitric oxide donor, in rat carotid artery intimal injury.
Authors: J P Guo, K A Milhoan, R S Tuan, A M Lefer
Journal: Circulation Research (1994)

We studied the effects of an organic nitric oxide (NO) donor SPM-5185 in a rat carotid artery intimal injury model. Seven days after injury, the two end segments of the injured carotid arteries were studied for endothelial release of NO, and the middle segments were used for histological measurement of the intimal-to-medial (I/M) ratio and scanning electron microscopy of the luminal surface. The NO donor SPM-5185 or its non-NO-donating control compound SPM-5267 were infused intravenously at 30 micrograms/d. Full vasorelaxant responses of rat carotid arterial rings were obtained with the endothelium-dependent vasodilators acetylcholine (ACh), A23187, and the endothelium-independent vasodilator acidified NaNO2 in sham-operated control rings. Impaired relaxation occurred with 10 mumol/L ACh and 1 mumol/L A23187 in injured rings but not in rings infused with SPM-5185 for 7 days. Relaxation to 100 mumol/L acidified NaNO2 was not significantly different among any of the groups, indicating a normal vascular smooth muscle response after intimal injury. Morphometric analysis of injured carotid arteries given vehicle and SPM-5267 showed marked intimal thickening with an average I/M ratio of 0.78 +/- 0.03 and 0.74 +/- 0.05, respectively. SPM-5185 markedly attenuated intimal thickening, resulting in an I/M ratio of 0.13 +/- 0.03 (P &lt; .01 from vehicle), representing an approximately 82% inhibition of intimal thickening. SPM-5185 infusion resulted in accelerated regeneration of endothelial cells on the intimal surface at 7 days.(ABSTRACT TRUNCATED AT 250 WORDS)
Vascular peroxidase 1/peroxidasin: a complex protein with a simple function?
Authors: R. P. Brandes
Journal: Cardiovascular Research (2011)

This editorial refers to ‘Involvement of vascular peroxidase 1 in angiotensin II-induced vascular smooth muscle cell proliferation’ by Ruizheng Shi et al ., doi:10.1093/cvr/cvr042 

Many cell culture and animal studies suggest that an increased formation of reactive oxygen species (ROS) promotes smooth muscle cell proliferation and matrix formation. It is therefore believed that increased ROS production contributes to such different entities as hypertension, restenosis, or arteriosclerosis. Initially, redox processes were believed to be mediated predominantly by hydrogen peroxide (H2O2). Over the years, however, many new aspects of redox signalling have been identified such as delicate alterations in the thiol redox state affecting the cellular redox potential, the complex interplay of nitric oxide with ROS, including the subsequent formation of peroxynitrite, and finally the involvement of peroxidases in redox signalling.1

Peroxidases catalyse the oxidation of a broad spectrum of substrates by H2O2, which, in the case of thyroid peroxidase, is needed for the oxidation of iodine and the formation of thyroid hormone (TPO), or in the case of myeloperoxidase (MPO) results in the formation of hypochlorous acid (HOCl), an important mediator of host defense.2 In the cardiovascular system, MPO contributes to vascular dysfunction; it promotes lipid peroxidation, scavenges nitric oxide and MPO products activate matrix metalloproteinases, promoting tissue remodelling that can result in atrial fibrillation.3

In addition to TPO and MPO, lactoperoxidase, eosinophil peroxidase, and salivary peroxidase belong to the …
Inverse background of Helicobacter pylori antibody and pepsinogen in reflux oesophagitis compared with gastric cancer: analysis of 5732 Japanese subjects
Authors: Y Yamaji
Journal: Gut (2001)

<h3>BACKGROUND</h3> The relationship between <i>Helicobacter pylori</i> and reflux oesophagitis remains controversial. <h3>AIMS</h3> To evaluate the relationship between <i>H pylori</i> and reflux oesophagitis in a large number of Japanese subjects. <h3>SUBJECTS</h3> A total of 5732 consecutive Japanese subjects during a health screening were enrolled. <h3>METHODS</h3> Gastrointestinal endoscopy was performed on all subjects. We simultaneously measured serum anti-<i>H pylori</i> antibody and pepsinogen as markers of <i>H pylori</i> infection together with gastric atrophy. The risk of reflux oesophagitis was evaluated in relation to these markers, and the results were compared with those of gastric cancer. <h3>RESULTS</h3> Reflux oesophagitis was found in 108 subjects. Both positivity for<i>H pylori</i> antibody (adjusted odds ratio (OR) 0.67 (95% confidence interval 0.45–1.0)) and "low" pepsinogen indicating gastric atrophy (OR 0.35 (0.18–0.68)) were negatively associated with reflux oesophagitis. After subjects were classified into four groups based on positivity or negativity for <i>H pylori</i> antibody and "low" pepsinogen, the prevalence of reflux oesophagitis showed a decreasing trend as <i>H pylori</i> induced gastric atrophy became more severe. The risk of gastric cancer showed an increasing trend, exactly the opposite to that of reflux oesophagitis. <h3>CONCLUSIONS</h3> Analysis of a large series of Japanese subjects revealed a decreasing prevalence of reflux oesophagitis in conjunction with progress of gastric atrophy induced by <i>H pylori</i> infection. This pattern was completely opposite to that of gastric cancer cases. A protective role of <i>H pylori</i> for reflux oesophagitis through the development of gastric atrophy has been suggested.
Characterization of Novel Alu- and tRNA-Related SINEs from the Tree Shrew and Evolutionary Implications of Their Origins
Authors: Hidenori Nishihara, Yohey Terai, Norihiro Okada
Journal: Molecular Biology and Evolution (2002)

We characterized two novel 7SL RNA-derived short interspersed nuclear element (SINE) families (Tu types I and II) and a novel tRNA-derived SINE family (Tu type III) from the tree shrew (Tupaia belangeri). Tu type I contains a monomer unit of a 7SL RNA-derived Alu-like sequence and a tRNA-derived region that includes internal RNA polymerase III promoters. Tu type II has a similar hybrid structure, although the monomer unit of the 7SL RNA-derived sequence is replaced by a dimer. Along with the primate Alu, the galago Alu type II, and the rodent B1, these two families represent the fourth and fifth 7SL RNA-derived SINE families to be identified. Furthermore, comparison of the Alu domains of Tu types I and II with those of other 7SL RNA-derived SINEs reveals that the nucleotides responsible for stabilization of the Alu domain have been conserved during evolution, providing the possibility that these conserved nucleotides play an indispensable role in retropositional activity. Evolutionary relationships among these 7SL RNA-derived SINE families, as well as phylogenetic relationships of their host species, are discussed.
Justifying the Choice of Endpoints for Clinical Trials
Authors: C. B. Begg
Journal: JNCI Journal of the National Cancer Institute (2013)

correlating the effect size of the treatment on OS with the corresponding effect size on the surrogate endpoint. Strong congruence of the effect sizes of the two endpoints supports the premise that the surrogate endpoint is a valid replacement for OS, although the strength of the statistical measure can be strongly dependent on the range of effect sizes observed in the historical studies. The meta-analysis of Oba et al. demonstrates impressively close concordance of the effects of treatment on OS and DFS from 14 historical adjuvant trials of gastric cancer (5). These results exemplify the fact that in the adjuvant setting disease recurrence is a pivotal event in the natural history of the disease for most solid tumors. Recurrence predicts strongly ultimate death from disease. Indeed the rank correlation between DFS
Regulation of gastric function by endogenous gastrin releasing peptide in humans: studies with a specific gastrin releasing peptide receptor antagonist
Authors: P Hildebrand
Journal: Gut (2001)

<h3>BACKGROUND AND AIMS</h3> The main goal of our study was to characterise the activity of BIM26226 as a peripheral gastrin releasing peptide (GRP) receptor antagonist in healthy human subjects and to determine if endogenous GRP is a physiological regulator of gastric acid secretion and gastrin release. <h3>METHODS</h3> Our study consisted of three parts. In part I, subjects received saline or BIM26226 followed by graded doses of intravenous human GRP in a four period crossover design. In part II, subjects received BIM26226 or saline during oral meal ingestion or modified sham feeding. In part III, subjects received an acidified meal in the presence and absence of BIM26226 in a two period crossover design. In addition, gastrin and somatostatin mRNA were measured in biopsy specimens during saline and BIM26226 infusion. <h3>RESULTS</h3> BIM26226 dose dependently inhibited GRP induced acid output. Acid secretion after oral liquid meal intake and sham feeding was significantly inhibited by BIM26226 (p&lt;0.01) whereas plasma gastrin release remained unchanged. Gastrin and somatostatin mRNAs were not significantly different after saline or BIM26226. <h3>CONCLUSIONS</h3> BIM26226 is a potent GRP antagonist in humans. Endogenous GRP may be a physiological regulator of gastric acid secretion. Gastrin release does not seem to be under the control of GRP.