tbuckley/cabot-search huggingface dataset:
Potential Mechanisms by Which Polyphenol-Rich Grapes Prevent Obesity-Mediated Inflammation and Metabolic Diseases
Authors: Chia-Chi Chuang, Michael K. McIntosh
Journal: Annual Review of Nutrition (2011)

Obesity and metabolic disease-related health problems (e.g., type 2 diabetes, atherosclerosis, and hypertension) are the most prevalent nutrition-related issues in the United States. An emerging feature of obesity and type 2 diabetes is their linkage with chronic inflammation that begins in white adipose tissue and eventually becomes systemic. One potential strategy to reduce inflammation and insulin resistance is consumption of polyphenol-rich foods like grapes or their by-products, which have anti-inflammatory properties. Polyphenols commonly found in grape products have been reported to reduce inflammation by (a) acting as an antioxidant or increasing antioxidant gene or protein expression, (b) attenuating endoplasmic reticulum stress signaling, (c) blocking proinflammatory cytokines or endotoxin-mediated kinases and transcription factors involved in metabolic disease, (d) suppressing inflammatory- or inducing metabolic-gene expression via increasing histone deacetylase activity, or (e) activating transcription factors that antagonize chronic inflammation. Thus, polyphenol-rich grape products may reduce obesity-mediated chronic inflammation by multiple mechanisms, thereby preventing metabolic diseases.
The Control of Copy Number of IS6110 in Mycobacterium tuberculosis
Authors: M. M. Tanaka
Journal: Molecular Biology and Evolution (2004)

Insertion sequence (IS) elements are bacterial genes that are able to transpose to different locations in the genome. These elements are often used in molecular epidemiology as genetic markers that track the spread of pathogens. Transposable elements have frequently been described as "selfish DNA" because they facilitate their own transposition, causing damage when they insert into coding regions, while contributing little if anything to the bacterial host. According to this hypothesis, the expansion of copy number of insertion sequences is opposed by negative selection against high copy numbers. From an alternative point of view, we might expect IS elements to intrinsically regulate transposition within cells, thereby limiting damage to their bacterial host. Here, we report evidence that the copy number of IS6110 in Mycobacterium tuberculosis is controlled by selection against the element. We first construct 12 different models of marker change resulting from a combination of possible transposition functions and selective regimes. We then compute the Akaike Information Criterion for each model to identify the models that best explain data consisting of serial isolates of M. tuberculosis genotyped with IS6110. We find that the best performing models all include selection against the accumulation of copies. Specifically, our analysis points to the interaction of separate copies of the element causing lethal effects. We discuss the implications of these findings for genome evolution and molecular epidemiology.
Six-minute walk distance is a surrogate parameter of physical activity in patients with idiopathic pulmonary fibrosis
Authors: Akira Morino, Hiroki Takahashi, Sumio Ishiai
Journal: European Respiratory Journal (2013)

Rationale   The previous studies reported that physical activity (PA) was one of the important factors associated with health-related quality of life (HRQOL) in patients with idiopathic pulmonary fibrosis (IPF). PA was assessed correctly by a mean of daily step counts during 2 weeks, but this method was time-consuming. The aims of this study were to find the surrogate parameters for PA and to reconfirm the relationships between PA and HRQOL in patients with IPF.   Methods   Our study included 38 outpatients with IPF and a mean age of 71.3 years, who visited the Sapporo Medical University hospital from October 2011 to June 2012. The mean number of steps per day during 2 weeks was recorded with the uniaxial accelerometer and used as an index of PA. We measured the clinical characteristics, pulmonary, physical and mental functions, and HRQOL. Multiple regression analysis was used to reveal the parameters that affected PA.   Results   The mean PA was 5146.4 (steps/day) and statistically correlated with age (r = -0.646; p  2  = 0.575; p    Conclusion   PA of patients with IPF correlate with their HRQOL and the appropriate surrogate parameters of PA may be age and 6MWD.
Cell cultures from bronchial subepithelial myofibroblasts enhance eosinophil survival in vitro
Authors: S Zhang, Q Mohammed, A Burbidge, CM Morland, WR Roche
Journal: European Respiratory Journal (1996)

Mechanisms of eosinophil accumulation and activation in the bronchial mucosa are crucial for the pathogenesis of asthma. The location of specialized fibroblasts, myofibroblasts, beneath the bronchial basement membrane and their proximity to infiltrating eosinophils potentially enable the myofibroblasts to modulate eosinophil survival and function in asthma. The aim of this study was to investigate the effects of bronchial myofibroblasts on eosinophil survival in vitro. Eosinophils from human peripheral blood were exposed to cell cultures from bronchial myofibroblasts and to myofibroblast-conditioned media. Eosinophil viability was assessed and granulocyte/macrophage colony-stimulating factor (GM-CSF) production was examined in co-culture supernatants and as messenger ribonucleic acid (mRNA) in myofibroblasts. Eosinophil survival was significantly increased and eosinophil apoptosis was inhibited by co-culture with myofibroblasts. Conditioned medium from tumour necrosis factor-alpha (TNF-alpha)-stimulated myofibroblasts also prolonged eosinophil survival. This effect could be blocked by GM-CSF antibody. GM-CSF mRNA and secretion from myofibroblasts were increased in co-cultures and by eosinophil-conditioned medium. Addition of antibodies to TNF-alpha and interleukin-1 alpha (IL-1 alpha) to co-cultures resulted in significant reduction both in eosinophil survival and GM-CSF levels. Blocking of fibronectin in the co-cultures did not affect the eosinophil survival enhancing activity. Prednisolone inhibited the eosinophil survival enhancing activity of the co-cultures by suppression of GM-CSF production. Soluble eosinophil-derived cytokines are involved in the interaction of eosinophils with myofibroblasts, which results in a tumour necrosis factor-alpha/interleukin-1 alpha mediated release of granulocyte/macrophage colony-stimulating factor from myofibroblasts. Bronchial myofibroblasts can, thereby, contribute to allergic inflammation by granulocyte/macrophage colony-stimulating factor-mediated inhibition of eosinophil apoptosis.
Birth characteristics and asthma symptoms in young adults: results from a population-based cohort study in Norway
Authors: C Svanes, E Omenaas, JM Heuch, LM Irgens, A Gulsvik
Journal: European Respiratory Journal (1998)

There is evidence that the origin of obstructive lung disease may be traced back to foetal life. The associations between birth characteristics and asthma symptoms were studied in a random population sample of young Norwegian adults. Respiratory symptoms were recorded in a population-based questionnaire survey. The records of all subjects aged 20-24 yrs were linked with the Medical Birth Registry of Norway. Of 868 subjects born in Norway, there were 690 (79%) responders. The associations between asthma symptoms and birth characteristics were analysed by logistic regression, adjusted for possible confounding factors. Asthma symptoms in young adults were inversely associated with birth weight (odds ratio (OR)wheeze=0.82; 95% confidence interval (CI)=0.69-0.96x500 g increase in birth weight(-1))), and after adjustment for gestational age, birth length, parity and maternal age (ORwheeze=0.69; 95% CI=0.50-0.95x500 g increase in birth weight(-1)). The association did not vary according to adult smoking habits or atopic status and remained when premature and low weight births were excluded (ORwheeze=0.73; 95% CI=0.60-0.90x500 g increase in birth weight(-1)). The association was consistent for all asthma symptoms. Adjusted for birth weight, asthma symptoms were further associated with low gestational age, high birth length and low maternal age. In a random sample of young adults, asthma symptoms were strongly associated with low birth weight, an association driven by the full-term births within the normal birth weight range. The findings show that the risk for adult asthma is partly established early in life and suggest that poor intrauterine growth is involved in the aetiology of asthma.
Estimating synonymous and nonsynonymous substitution rates
Authors: S. V. Muse
Journal: Molecular Biology and Evolution (1996)

Partitioning the total substitution rate into synnonymous and nonsynonymous components is a key aspect of many analyses in molecular evolution. Numerous methods exist for estimating these rates. However, until recently none of the estimation procedures were based on a sound statistical footing. In this paper, the evolutionary model of Muse and Gaut (1994) is used as the basis for two sets of parameters quantifying silent and replacement substitution rates. The parameters are shown to be equal when the four nucleotides are equally frequent and unequal otherwise. Maximum-likelihood estimation of these parameters is described, and the performance of these estimates is compared to that of existing estimation procedures. It is shown that the estimates of Nei and Gojobori (1986) are not unbiased for either set of parameters, although they provide very good estimates for one set as long as sequence divergence is not too high. However, some disturbing properties are found for the Nei and Gojobori estimates. In particular, it is shown that the expected value of the Nei and Gojobori estimate of silent substitution rate is a function of both the silent and replacement substitution rates. The maximum-likelihood estimates have no such problems.
Splicing regulator SLU7 is essential for maintaining liver homeostasis
Authors: María Elizalde, Raquel Urtasun, María Azkona, María U. Latasa, Saioa Goñi, Oihane García-Irigoyen, Iker Uriarte, Victor Segura, María Collantes, Mariana Di Scala, Amaia Lujambio, Jesús Prieto, Matías A. Ávila, Carmen Berasain
Journal: Journal of Clinical Investigation (2014)

A precise equilibrium between cellular differentiation and proliferation is fundamental for tissue homeostasis. Maintaining this balance is particularly important for the liver, a highly differentiated organ with systemic metabolic functions that is endowed with unparalleled regenerative potential. Carcinogenesis in the liver develops as the result of hepatocellular de-differentiation and uncontrolled proliferation. Here, we identified SLU7, which encodes a pre-mRNA splicing regulator that is inhibited in hepatocarcinoma, as a pivotal gene for hepatocellular homeostasis. SLU7 knockdown in human liver cells and mouse liver resulted in profound changes in pre-mRNA splicing and gene expression, leading to impaired glucose and lipid metabolism, refractoriness to key metabolic hormones, and reversion to a fetal-like gene expression pattern. Additionally, loss of SLU7 also increased hepatocellular proliferation and induced a switch to a tumor-like glycolytic phenotype. Slu7 governed the splicing and/or expression of multiple genes essential for hepatocellular differentiation, including serine/arginine-rich splicing factor 3 (Srsf3) and hepatocyte nuclear factor 4α (Hnf4α), and was critical for cAMP-regulated gene transcription. Together, out data indicate that SLU7 is central regulator of hepatocyte identity and quiescence.
Does plyometric training improve vertical jump height? A meta-analytical review
Authors: Goran Markovic
Journal: British Journal of Sports Medicine (2007)

The aim of this study was to determine the precise effect of plyometric training (PT) on vertical jump height in healthy individuals. Meta-analyses of randomised and non-randomised controlled trials that evaluated the effect of PT on four typical vertical jump height tests were carried out: squat jump (SJ); countermovement jump (CMJ); countermovement jump with the arm swing (CMJA); and drop jump (DJ). Studies were identified by computerised and manual searches of the literature. Data on changes in jump height for the plyometric and control groups were extracted and statistically pooled in a meta-analysis, separately for each type of jump. A total of 26 studies yielding 13 data points for SJ, 19 data points for CMJ, 14 data points for CMJA and 7 data points for DJ met the initial inclusion criteria. The pooled estimate of the effect of PT on vertical jump height was 4.7% (95% CI 1.8 to 7.6%), 8.7% (95% CI 7.0 to 10.4%), 7.5% (95% CI 4.2 to 10.8%) and 4.7% (95% CI 0.8 to 8.6%) for the SJ, CMJ, CMJA and DJ, respectively. When expressed in standardised units (ie, effect sizes), the effect of PT on vertical jump height was 0.44 (95% CI 0.15 to 0.72), 0.88 (95% CI 0.64 to 1.11), 0.74 (95% CI 0.47 to 1.02) and 0.62 (95% CI 0.18 to 1.05) for the SJ, CMJ, CMJA and DJ, respectively. PT provides a statistically significant and practically relevant improvement in vertical jump height with the mean effect ranging from 4.7% (SJ and DJ), over 7.5% (CMJA) to 8.7% (CMJ). These results justify the application of PT for the purpose of development of vertical jump performance in healthy individuals.
Response to Paclitaxel, Topotecan, and Topotecan-Cyclophosphamide in Children With Untreated Disseminated Neuroblastoma Treated in an Upfront Phase II Investigational Window: A Pediatric Oncology Group Study
Authors: Cynthia S. Kretschmar, Morris Kletzel, Kevin Murray, Paul Thorner, Vijay Joshi, Robert Marcus, E. Ide Smith, Wendy B. London, Robert Castleberry
Journal: Journal of Clinical Oncology (2004)

Purpose Most children older than 1 year of age with metastatic neuroblastoma (NB) die despite intensive chemotherapy and bone marrow transplantation. The Pediatric Oncology Group conducted a study of paclitaxel, topotecan, and topotecan-cyclophosphamide (topo-cyclo) in newly diagnosed children with stage IV NB. Patients and Methods There were 102 patients enrolled between September 1993 and October 1995; two of them were later shown to be ineligible. Of the remaining 100 patients, the first cohort of 33 patients received paclitaxel 350 mg/m 2 intravenously (IV) over 24 hours every 14 to 21 days; the next 33 patients received topotecan 2 mg/m 2 /d for 5 days IV every 21 days; a third cohort of 34 patients were treated with IV cyclophosphamide 250 mg/m 2 followed by topotecan 0.75 mg/m 2 each day for 5 days every 21 days. Patients were re-evaluated after two courses and then treated with intensive induction therapy and bone marrow transplantation. Results Objective responses (complete response + partial response + mixed response) were documented in 67% of children who received topotecan, 76% after topo-cyclo, and 25% after paclitaxel. Four patients had grade 3 to 4 allergic reactions to paclitaxel; most patients developed grade 3 to 4 marrow suppression after topotecan or topo-cyclo. Neither disease-free survival nor overall survival differed significantly between children who received a phase II agent and those who did not. The 6-year disease-free survival and overall survival rates for all 100 children were 18% ± 5% and 26% ± 5%, respectively. Conclusion Topotecan and topo-cyclo are active in children with NB, are well tolerated, and should be evaluated further in combination regimens.
Advances in Radiotherapy for Head and Neck Cancer
Authors: Vincent Grégoire, Johannes A. Langendijk, Sandra Nuyts
Journal: Journal of Clinical Oncology (2015)

Over the last few decades, significant improvements have been made in the radiotherapy (RT) treatment of head and neck malignancies. The progressive introduction of intensity-modulated RT and the use of multimodality imaging for target volume and organs at risk delineation, together with the use of altered fractionation regimens and concomitant administration of chemotherapy or targeted agents, have accompanied efficacy improvements in RT. Altogether, such improvements have translated into improvement in locoregional control and overall survival probability, with a decrease in the long-term adverse effects of RT and an improvement in quality of life. Further progress in the treatment of head and neck malignancies may come from a better integration of molecular imaging to identify tumor subvolumes that may require additional radiation doses (ie, dose painting) and from treatment adaptation tracing changes in patient anatomy during treatment. Proton therapy generates even more exquisite dose distribution in some patients, thus potentially further improving patient outcomes. However, the clinical benefit of these approaches, although promising, for patients with head and neck cancer need to be demonstrated in prospective randomized studies. In this context, our article will review some of these advances, with special emphasis on target volume and organ-at-risk delineation, use of molecular imaging for tumor delineation, dose painting for dose escalation, dose adaptation throughout treatment, and potential benefit of proton therapy.
Two months auto-adjusting versus conventional nCPAP for obstructive sleep apnoea syndrome
Authors: H Teschler, T.e Wessendorf, A.a Farhat, N Konietzko, M. Berthon-Jones
Journal: European Respiratory Journal (2000)

Autoadjusting nasal continuous positive airway pressure (CPAP) greatly reduces the apnoea/hypopnoea index (AHI), and affords a significant reduction in median pressure (P50) compared-with manually titrated conventional nasal CPAP. The aim of the present study was to test whether these benefits were maintained in the medium term at home, in a double-blind crossover study. Ten sequential subjects (mean AHI 52.9 x h(-1)) were enrolled. After a manual titration, subjects were randomly allocated to 2 months autoadjusting nasal CPAP (AutoSet), followed by 2 months with the AutoSet device in fixed pressure mode at the manually titrated pressure, or vice versa. The machine-scored AHI, P50, and median leak were recorded on 12 nights in each arm, and averaged. Mean+/-SEM AHI was 4.0+/-0.3 x h(-1) in auto mode, and 3.7+/-0.3 x h(-1) in manual mode (NS). Mean+/-SEM P50 was 7.2+/-0.4 cmH2O auto, 9.4+/-0.6 cmH2O manual, average reduction 23+/-4% (p&lt;0.0001). Auto "recommended" pressure was (mean+/-SEM) 10.1+/-0.5 cmH2O (p=0.04 with respect to manual) and peak pressure typically 1 cmH2O higher. Median (+/-SEM) leak was 0.181+/-0.006 L x s(-1) auto (and uncorrelated with AHI or pressure), 0.20+/-0.006 L x s(-1) manual (p=0.003). Compliance was 6.3+/-0.4 h in auto mode and 6.1+/-0.5 h in fixed mode (NS). Apnoea/hypopnoea index during 2 months of home autoadjusting nasal continuous positive airway pressure is comparable to that during conventionally titrated fixed pressure continuous positive airway pressure, while affording a 23% reduction in median pressure but no increase in compliance. Leak did not importantly affect autoadjustment.
The conversion of testosterone to 5α-Androstan-17β-ol-3-one (dihydrotestosterone) by Skin Slices Of man
Authors: Jean D. Wilson, Joanne D. Walker
Journal: Journal of Clinical Investigation (1969)

The conversion of testosterone-1,2-3H to dihydrotestosterone by slices of human skin obtained from various anatomical sites in 112 normal subjects and three individuals with the syndrome of testicular feminization has been measured under standardized conditions. Very low rates of dihydrotestosterone formation were observed in sites obtained from the mons or from miscellaneous areas of the trunk and limbs of the control subjects. The mean rates of conversion were very high, however, in slices of skin obtained from several perineal sites (labia majora, scrotum, prepuce, and clitoris). Furthermore, as measured here, the rate of dihydrotestosterone formation by prepuce rises during the 3 months after birth and then falls progressively thereafter, reaching a level in the adult that is almost as low as that observed in the slices of nonperineal skin from all ages. In the patients with testicular feminization dihydrotestosterone formation by slices of skin obtained from the mons was within the normal range, whereas the rates observed in labia majora were lower than the average values obtained in the normal subjects.
Proteome-wide evidence for enhanced positive Darwinian selection within intrinsically disordered regions in proteins
Authors: Johan Nilsson, Mats Grahn, Anthony PH Wright
Journal: Genome biology (2011)

Abstract Background Understanding the adaptive changes that alter the function of proteins during evolution is an important question for biology and medicine. The increasing number of completely sequenced genomes from closely related organisms, as well as individuals within species, facilitates systematic detection of recent selection events by means of comparative genomics. Results We have used genome-wide strain-specific single nucleotide polymorphism data from 64 strains of budding yeast ( Saccharomyces cerevisiae or Saccharomyces paradoxus ) to determine whether adaptive positive selection is correlated with protein regions showing propensity for different classes of structure conformation. Data from phylogenetic and population genetic analysis of 3,746 gene alignments consistently shows a significantly higher degree of positive Darwinian selection in intrinsically disordered regions of proteins compared to regions of alpha helix, beta sheet or tertiary structure. Evidence of positive selection is significantly enriched in classes of proteins whose functions and molecular mechanisms can be coupled to adaptive processes and these classes tend to have a higher average content of intrinsically unstructured protein regions. Conclusions We suggest that intrinsically disordered protein regions may be important for the production and maintenance of genetic variation with adaptive potential and that they may thus be of central significance for the evolvability of the organism or cell in which they occur.
Geldanamycin and herbimycin A induce apoptotic killing of B chronic lymphocytic leukemia cells and augment the cells' sensitivity to cytotoxic drugs
Authors: Dylan T. Jones, Elena Addison, Janet M. North, Mark W. Lowdell, A. Victor Hoffbrand, Atul B. Mehta, Kanagasabai Ganeshaguru, Najeem I. Folarin, R. Gitendra Wickremasinghe
Journal: Blood (2003)
'Fiddler's neck'
Authors: R.D.G. PEACHEY, C.N.A. MATTHEWS
Journal: British Journal of Dermatology (1978)

'Fiddler's neck' is a condition affecting violin and viola players. Although well known to musicians it is not well recognized by dermatologists. Clinically the lesions usually consist of a localized area of lichenification of the left side of the neck--just below the angle of the jaw. Pigmentation, erythema and inflammatory papules or pustules are frequently present, while severe inflammatory induration, cyst formation and scarring occur in more severely affected subjects. The aetiology of the skin changes is probably due to a combination of factors; friction giving rise to lichenification, while local pressure, shearing stress and occlusion may play a part in producing the acne-like changes and cyst formation. In addition, poor hygiene may predispose to local sepsis.
ECG for risk stratification in patients with pulmonary embolism
Authors: D. Jimenez
Journal: European Respiratory Journal (2005)

K. Jung mentioned, we did not evaluate the influence of blood sampling and separation of serum from blood cells.We agree with M. John and K. Jung that we must be aware of pre-analytical problems when analysing the circulating matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)-1 levels.However, we used only serum samples in our study because we usually use serum samples for clinical examinations in our hospital.Therefore, we think that the comparison of the serum TIMP-1 and MMP-9 concentrations in each patient group is valid.Our results are consistent with serum TIMP-1 and MMP-9 concentrations reported elsewhere [2,3].