tbuckley/cabot-search huggingface dataset:
Does mild resistance training resemble a similar stimulus compared to aerobic training?
Authors: Dominik Pesta, Martin Burtscher
Journal: Hepatology (2013)

We read with interest the article recently published by Bacchi et al.1 and would like to provide a few comments on the article. Nonalcoholic fatty liver disease (NAFLD) is now becoming the most common liver disease in the world2 and Bacchi et al.1 were able to demonstrate that exercise per se is effective in decreasing hepatic fat content and improving hepatic steatosis of adults suffering from type 2 diabetes and NAFLD. The data provide an important contribution to the highly relevant “exercise is medicine” paradigm, which further gains ground by evidence presented in the work of Bacchi et al.1 In our opinion, however, it would be important to match energy expenditure of both interventions. Descriptions of the volume of resistance training (RT) seem inappropriate and difficult to comprehend, leaving some aspects unclear, e.g., was the weight adjusted to match the progress of the subjects? Further, hepatic fat content is ∼20% higher in the RT compared to the aerobic training (AT) group, whereas caloric intake is ∼15% lower. The point we want to make here is that especially in untrained subjects with a body mass index (BMI) of about 30 with probably little or no previous experience in exercise training, the stimulus of RT resembles more an AT stimulus. Whereas classic RT is characterized by an increase in muscle mass and muscle cross-sectional area, untrained subjects probably do not reach the threshold that is necessary for these adaptations to occur. Therefore, the mild RT carried out provokes a similar response comparable to the AT in this study despite very distinct pathways that are activated during classic RT.3 The similar effect of both interventions is indicative of a similar stimulus. We want to emphasize that it is necessary to distinguish between mild RT resembling more an AT stimulus and the classic RT that is commonly known when confronted with the term RT. The same phenomenon was observed by our group when conducting a training study with untrained people (BMI ∼26) who were subjected to either strength or endurance training.4 After 10 weeks of training, we saw similar increases in the capacity to oxidize fatty acids in both groups. In conclusion, RT carried out by well-trained athletes cannot be compared to the mild, resistance-type (circuit) training providing a distinct stimulus. Dominik Pesta, Ph.D.1,2Martin Burtscher, M.D., Ph.D.3 1Howard Hughes Medical InstituteYale University School of Medicine New Haven, CT2Department of Internal MedicineYale University School of MedicineNew Haven, CT3Department of Sports ScienceUniversity of InnsbruckInnsbruck, Austria
Sympathetic input into the enteric nervous system
Authors: O Lundgren
Journal: Gut (2000)

The basic concepts of the autonomic nervous system of organs and tissues were formulated around the turn of the century and summarised in a classical monograph by Langley (1921).1 The detailed distribution of the sympathetic nerves was, however, not elucidated until it became possible to stain sympathetic neurones specifically using the Falck-Hillarp technique. When this technique was applied to the gastrointestinal tract the picture seen was in some respects surprising. At the time it was generally believed that most organs and tissues had a dual innervation (sympathetic and parasympathetic) with opposite effects on function. It seemed, therefore, puzzling when the Falck-Hillarp technique revealed that innervation of a major part of the gastrointestinal wall, the smooth muscle layers, was very scarce. Instead it was found that most adrenergic fibres make contact with one of the two major plexuses in the alimentary canal. Adrenergic innervation is seen in the mucosa, in particular around the crypt epithelium.2 The functional consequences of this distribution are discussed below.

This brief review of the interplay between the sympathetic and enteric nervous systems will discuss the control of blood vessels, epithelial transport, motility, and endocrine cells (the enterochromaffin cells in particular).

There is dense adrenergic innervation of both precapillary and postcapillary vessels in the digestive tract. Stimulating the sympathetic nerves to the gut elicits a blood flow response which is very characteristic. Immediately on electrically stimulating the splanchnic nerves, pronounced vasoconstriction is observed which, however, subsides within a few minutes to reach a steady state level of blood flow. It seems probable that flow during steady state represents the “physiological” response to nerve activation. Intestinal flow resistance is thus only moderately increased (2–3 times) even when stimulating the sympathetic vasoconstrictor nerves at high rates (8–16 Hz). When investigating blood flow distribution within the intestinal wall …
Respiratory health in children, and indoor exposure to (1,3)- -D-glucan, EPS mould components and endotoxin
Authors: C. Tischer, U. Gehring, C.-M. Chen, M. Kerkhof, G. Koppelman, S. Sausenthaler, O. Herbarth, B. Schaaf, I. Lehmann, U. Kramer, D. Berdel, A. von Berg, C. P. Bauer, S. Koletzko, H.-E. Wichmann, B. Brunekreef, J. Heinrich
Journal: European Respiratory Journal (2010)

For a long time, exposure to mould and dampness-derived microbial components was considered a risk factor for the development of respiratory diseases and symptoms. Some recent studies suggested that early childhood exposure to mould components, such as (1,3)-β-d-glucan and extracellular polysaccharides (EPSs), may protect children from developing allergy. We investigated the association of exposure to (1,3)-β-d-glucan, EPS and endotoxin with asthma and allergies in 6-yr-old children. This investigation was the follow-up to a nested case–control study among three European birth cohorts. Children from two ongoing birth cohort studies performed in Germany (n = 358) and one in the Netherlands (n = 338) were selected. Levels of (1,3)-β-d-glucan, EPS and endotoxin were measured in settled house dust sampled from children's mattresses and living-room floors when the children were, on average, 5 yrs of age. At the age of 6 yrs, health outcome information was available for 678 children. In the two German subsets, domestic EPS and endotoxin exposure from children's mattresses were significantly negatively associated with physician-diagnosed asthma (OR per interquartile range increase 0.60 (95% CI 0.39–0.92) and 0.55 (95% CI 0.31–0.97), respectively). In addition, EPS exposure was inversely related to physician-diagnosed allergic rhinitis (OR 0.50, 95% CI 0.31–0.81). For the Dutch population, no associations were observed between exposure to microbial agents and respiratory health outcomes. We found inverse associations between domestic exposure to EPS and endotoxin from children's mattresses, and doctor-diagnosed asthma and rhinitis in German, but not in Dutch, school children. The reasons for the differences between countries are not clear.
Comparison of a cardiorespiratory device<i>versus</i>polysomnography for diagnosis of sleep apnoea
Authors: J.M. Calleja, S. Esnaola, R. Rubio, J. Durán
Journal: European Respiratory Journal (2002)

This study assessed the accuracy of a cardiorespiratory monitoring device versus polysomnography for the diagnosis of suspected sleep apnoea/hypoponea syndrome (SAS). A total of 86 patients (89% male, mean age 52 yrs) that had been referred to a sleep laboratory with a clinical diagnosis of SAS underwent cardiorespiratory polygraphy in an unattended mode using an ambulatory device (MERLIN). Analysis was carried out both automatically and manually. Conventional overnight full-channel polysomnography was performed simultaneously. Valid polygraphical recordings were obtained from 79 patients. The mean±sd apnoea/hypopnoea index (AHI) was 34.4±29.2. The results obtained with manual scoring were superior to automatic scoring for all AHI thresholds. For an AHI of ≥5, which is diagnostic SAS, the optimum cut-off value for the manual respiratory event index was 6.7 and the cardiorespiratory monitoring device had 97.1% sensitivity and 90.9% specificity. Correct classification according to the different cut-off points obtained via polysomnography and the corresponding cut-off points in the MERLIN manual index were confirmed in 90–96% of patients. The MERLIN device is a useful diagnostic approach for the initial assessment of adult patients with clinical suspicion of sleep apnoea/hypopnoea syndrome. Manual scoring is clearly better than automatic scoring in terms of agreement with the apnoea/hypopnoea index and to discern patients with sleep apnoea/hypopnoea syndrome.
Vascular adhesion molecule–1 and intercellular adhesion molecule–1 expression on rat liver cells after lipopolysaccharide administrationin vivo
Authors: Marijke van Oosten, Erika van de Bilt, Helga E. de Vries, Theo J. C. van Berkel, Johan Kuiper
Journal: Hepatology (1995)

During sepsis the infiltration of leukocytes plays a pivotal role in tissue damage. Induction of septic shock results in an early accumulation of polymorphonuclear leukocytes in the liver (after 3 hours), which is followed by an infiltration of mononuclear phagocytes (after 30 hours). Expression of adhesion molecules may contribute to the migration of leukocytes to the site of inflammation. Therefore, in the present study we determined the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) on hepatocytes, liver endothelial cells, and Kupffer cells after lipopolysaccharide (LPS) treatment of rats in vivo. Parenchymal cells showed no constitutive expression of VCAM-1 and the expression could not be upregulated by LPS treatment in vivo, whereas Kupffer and endothelial cells had a low basal expression of VCAM-1 and this expression was increased 40-fold by LPS treatment in vivo. All three cell types showed a basal expression of ICAM-1 and the expression on endothelial liver cells of untreated rats was two times higher than the expression on parenchymal and Kupffer cells. Stimulation with LPS increased the expression of ICAM-1 2.5 times per parenchymal cells and approximately 4 times for endothelial and Kupffer cells. It is concluded that the expression of adhesion molecules may contribute to the influx of leukocytes during septic shock and, therefore, play a role in tissue damage during septic shock.
Control of Cholesterol Metabolism and Plasma High-Density Lipoprotein Levels by microRNA-144
Authors: Cristina M. Ramírez, Noemi Rotllan, Alexander V. Vlassov, Alberto Dávalos, Mu Li, Leigh Goedeke, Juan F. Aranda, Daniel Cirera-Salinas, Elisa Araldi, Alessandro Salerno, Amarylis Wanschel, Jiri Zavadil, Antonio Castrillo, Jungsu Kim, Yajaira Suárez, Carlos Fernández-Hernando
Journal: Circulation Research (2013)

Rationale: Foam cell formation because of excessive accumulation of cholesterol by macrophages is a pathological hallmark of atherosclerosis, the major cause of morbidity and mortality in Western societies. Liver X nuclear receptors (LXRs) regulate the expression of the adenosine triphosphate–binding cassette (ABC) transporters, including adenosine triphosphate–binding cassette transporter A1 (ABCA1) and adenosine triphosphate–binding cassette transporter G1 (ABCG1). ABCA1 and ABCG1 facilitate the efflux of cholesterol from macrophages and regulate high-density lipoprotein (HDL) biogenesis. Increasing evidence supports the role of microRNA (miRNAs) in regulating cholesterol metabolism through ABC transporters. Objective: We aimed to identify novel miRNAs that regulate cholesterol metabolism in macrophages stimulated with LXR agonists. Methods and Results: To map the miRNA expression signature of macrophages stimulated with LXR agonists, we performed an miRNA profiling microarray analysis in primary mouse peritoneal macrophages stimulated with LXR ligands. We report that LXR ligands increase miR-144 expression in macrophages and mouse livers. Overexpression of miR-144 reduces ABCA1 expression and attenuates cholesterol efflux to apolipoproteinA1 in macrophages. Delivery of miR-144 oligonucleotides to mice attenuates ABCA1 expression in the liver, reducing HDL levels. Conversely, silencing of miR-144 in mice increases the expression of ABCA1 and plasma HDL levels. Thus, miR-144 seems to regulate both macrophage cholesterol efflux and HDL biogenesis in the liver. Conclusions: miR-144 regulates cholesterol metabolism via suppressing ABCA1 expression and modulation of miRNAs may represent a potential therapeutical intervention for treating dyslipidemia and atherosclerotic vascular disease.
Correcting for Differential Transcript Coverage Reveals a Strong Relationship between Alternative Splicing and Organism Complexity
Authors: Lu Chen, Stephen J. Bush, Jaime M. Tovar-Corona, Atahualpa Castillo-Morales, Araxi O. Urrutia
Journal: Molecular Biology and Evolution (2014)

What at the genomic level underlies organism complexity? Although several genomic features have been associated with organism complexity, in the case of alternative splicing, which has long been proposed to explain the variation in complexity, no such link has been established. Here, we analyzed over 39 million expressed sequence tags available for 47 eukaryotic species with fully sequenced genomes to obtain a comparable index of alternative splicing estimates, which corrects for the distorting effect of a variable number of transcripts per species—an important obstacle for comparative studies of alternative splicing. We find that alternative splicing has steadily increased over the last 1,400 My of eukaryotic evolution and is strongly associated with organism complexity, assayed as the number of cell types. Importantly, this association is not explained as a by-product of covariance between alternative splicing with other variables previously linked to complexity including gene content, protein length, proteome disorder, and protein interactivity. In addition, we found no evidence to suggest that the relationship of alternative splicing to cell type number is explained by drift due to reduced Ne in more complex species. Taken together, our results firmly establish alternative splicing as a significant predictor of organism complexity and are, in principle, consistent with an important role of transcript diversification through alternative splicing as a means of determining a genome's functional information capacity.
PTEN inhibits BMI1 function independently of its phosphatase activity
Authors: Catherine Fan, Lizhi He, Anil Kapoor, Adrian P Rybak, Jason De Melo, Jean-Claude Cutz, Damu Tang
Journal: Molecular Cancer (2009)

PTEN is the second most mutated tumor suppressor gene other than p53. It suppresses tumorigenesis by dephosphorylating phosphatidylinositol (3,4,5)-triphosphate (PIP3) to phosphatidylinositol (4,5)-biphosphate (PIP2), thereby directly inhibiting phosphatidylinositol 3 kinase (PI3K)-mediated tumorigenic activities. Consistent with this model of action, cytosolic PTEN is recruited to the plasma membrane to dephosphorylate PIP3. While nuclear PTEN has been shown to suppress tumorigenesis by governing genome integrity, additional mechanisms may also contribute to nuclear PTEN-mediated tumor suppression. The nuclear protein BMI1 promotes stem cell self-renewal and tumorigenesis and PTEN inhibits these events, suggesting that PTEN may suppress BMI1 function.We investigated whether PTEN inhibits BMI1 function during prostate tumorigenesis. PTEN binds to BMI1 exclusively in the nucleus. This interaction does not require PTEN's phosphatase activity, as phosphatase-deficient PTEN mutants, PTEN/C124S (CS), PTEN/G129E (GE), and a C-terminal PTEN fragment (C-PTEN) excluding the catalytic domain, all associate with BMI1. Furthermore, the residues 186-286 of C-PTEN are sufficient for binding to BMI1. This interaction reduces BMI1's function. BMI1 enhances hTERT activity and reduces p16(INK4A) and p14(ARF) expression. These effects were attenuated by PTEN, PTEN(CS), PTEN(GE), and C-PTEN. Furthermore, knockdown of PTEN in DU145 cells increased hTERT promoter activity, which was reversed when BMI1 was concomitantly knocked-down, indicating that PTEN reduces hTERT promoter activity via inhibiting BMI1 function. Conversely, BMI1 reduces PTEN's ability to inhibit AKT activation, which can be attributed to its interaction with PTEN in the nucleus, making PTEN unavailable to dephosphorylate membrane-bound PIP3. Furthermore, BMI1 appears to co-localize with PTEN more frequently in clinical prostate tissue samples from patients diagnosed with PIN (prostatic intraepithelial neoplasia) and carcinoma compared to normal prostate epithelium. While PTEN co-localized with BMI1 in 2.4% of normal prostate epithelial cells, co-localization was observed in 37.6% and 18.5% of cells in PIN and carcinoma, respectively. Collectively, we demonstrate that PTEN inhibits BMI1 function via binding to BMI1 in a phosphatase independent manner.We demonstrate that nuclear PTEN reduces BMI1 function independently of its phosphatase activity. It was recently observed that nuclear PTEN also suppresses tumorigenesis. Our results, therefore, provide a plausible mechanism by which nuclear PTEN prevents tumorigenesis.
Hepatitis C Serotype and Response to Interferon Therapy
Authors: Liliana Chemello, Alfredo Alberti, Kenneth Rose, Peter Simmonds
Journal: New England Journal of Medicine (1994)

To the Editor: Hepatitis C virus (HCV) is a major cause of chronic liver disease and of hepatocellular carcinoma. Several strains of HCV exist; distinct genotypes can be identified by sequence comparison of the viral genomes.1 Recent evidence that the genotype of HCV may influence the clinical course of hepatitis C2 and the response to interferon therapy for this disease3 suggests that methods to identify the genotype may become clinically useful. Methods based on the polymerase chain reaction, however, are expensive, time-consuming, and limited to highly specialized laboratories. Serotype-specific immunodominant epitopes have recently been mapped to the NS4 region of . . .
Tuberculosis among Foreign-born Persons in the United States
Authors: Kevin P. Cain, Connie A. Haley, Lori R. Armstrong, Katie N. Garman, Charles D. Wells, Michael F. Iademarco, Kenneth G. Castro, Kayla F. Laserson
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Rationale: In the United States, the number of annual reported cases of tuberculosis (TB) among U.S.-born persons declined by 62% from 1993 to 2004, but increased by 5% among foreign-born persons. Over half of all reported cases of TB in the United States occur among foreign-born persons, most of these due to activation of latent TB infection (LTBI). Current guidelines recommend targeting only foreign-born persons who entered the United States within the previous 5 yr for LTBI testing.Objective: We sought to assess the epidemiologic basis for this guideline.Methods: We calculated TB case rates among foreign-born persons, stratified by duration of United States residence and world region of origin. We determined the number of cases using 2004 U.S. TB surveillance data, and calculated case rates using population data from the 2004 American Community Survey.Measurements and Main Results: In 2004, a total of 14,517 cases of TB were reported; 3,444 (24%) of these were among foreign-born persons who had entered the United States more than 5 yr previously. The rate of TB disease among foreign-born persons was 21.5/100,000, compared with 2.7/100,000 for U.S.-born persons, and varied by duration of residence and world region of origin.Conclusions: Almost one-quarter of all TB cases in the United States occur among foreign-born persons who have resided in the United States for longer than 5 yr; case rates for such persons from selected regions of origin remain substantially elevated. To eliminate TB, we must address the burden of LTBI in this high-risk group.
Glycemic Control Influences Serum Angiogenin Concentrations in Patients With Type 2 Diabetes
Authors: Janusz Siebert, Magdalena Reiwer-Gostomska, Jolanta Mysliwska, Natalia Marek, Krystyna Raczynska, Leopold Glasner
Journal: Diabetes Care (2010)

OBJECTIVE Because diabetes is the most frequent factor responsible for microvascular and macrovascular disease, we investigated angiogenin serum levels within the diabetic patient group. RESEARCH DESIGN AND METHODS We investigated 49 patients who met the criteria to be in the diabetic group. Forty nondiabetic patients were included in the control group. We set A1C &amp;lt;7% as well-controlled diabetes. Serum angiogenin level was measured using the enzyme-linked immunosorbent assay method. RESULTS Serum angiogenin levels of poorly controlled patients with type 2 diabetes were significantly lower than those of group with well-controlled diabetes (361.23 ± 126.03 ng/ml vs. 446.37 ± 134.10 ng/ml; P = 0.001). Moreover, they were characterized by a significantly longer duration of the disease (P = 0.006), higher BMI (P = 0.0003), and higher systolic blood pressure (P = 0.01). Levels of total cholesterol, triglycerides, LDL, and HDL were not significantly different in both groups. CONCLUSIONS Patients with poorly controlled type 2 diabetes (A1C &amp;gt;7%) have lower angiogenin levels than patients with well-controlled diabetes.
Heart Rate Predicts Outcomes in an Implantable Cardioverter-Defibrillator Population
Authors: Mastaneh Ahmadi-Kashani, David J. Kessler, John Day, T. Jared Bunch, Kira Q. Stolen, Scott Brown, Salam Sbaity, Brian Olshansky
Journal: Circulation (2009)

Background— Elevated heart rate (HR) is associated with adverse cardiovascular events and total mortality in the general population and in individuals with heart disease. Our hypothesis was that mean HR predicts total mortality and heart failure hospitalization in patients undergoing implantable cardioverter-defibrillator (ICD) implantation. Methods and Results— The Inhibition of Unnecessary RV Pacing With AV Search Hysteresis in ICDs (INTRINSIC RV) trial included 1530 patients undergoing ICD implantation. After implantation of a dual-chamber ICD, patients were followed for a mean of 10.4 months. The mean HR for 1436 patients over the follow-up period was determined from device histograms. Patients were grouped into strata by mean HR, and the relationship between the primary end point and mean HR was analyzed with Mantel-Haenszel ordinal χ 2 tests. Higher intrinsic (unpaced) HR was associated with greater risk of achieving the primary end point of death or heart failure hospitalization ( P &lt;0.001). Of patients with a mean HR &lt;75 bpm, 5.8% died or were hospitalized for heart failure, whereas 20.9% with a mean HR &gt;90 bpm achieved the same end point, a 3.6-fold difference ( P &lt;0.0001). In a multivariate model with the use of Cox regression, HR was a significant predictor with a hazard ratio of 1.34 ( P =0.0001; 95% confidence interval, 1.19 to 1.50), as were age, New York Heart Association functional class, and percent right ventricular pacing, but it was independent of gender and β-blocker dosing. When considered as continuous or discrete variables grouped by 5-bpm increments, HR remained a significant predictor. Conclusions— In this ICD population, the mean intrinsic HR was strongly associated with outcomes. Clinical Trial Registration— http://www.clinicaltrials.gov. Identifier: NCT00148967.