tbuckley/cabot-search huggingface dataset:
Effects of a 3-week inpatient pulmonary rehabilitation (PR) on muscle remodelling in patients with emphysema
Authors: Inga Heinzelmann, Sebastian Gehlert, Axel Clever, Christian Wingels, Bernd Sczepanski, Bloch Wilhelm, Kenn Klaus
Journal: European Respiratory Journal (2012)

Rationale:   Exercise training of at least 10 weeks duration induces significant changes in myofiber size, capillarization and distribution in patients with emphysema. Up to date it is unknown which changes in muscle structure can be achieved by a German inpatient PR with a standard duration of 3 weeks.   Methods:   Ten patients with emphysema (age: 57±5y; BMI: 24±3kg/m 2 ; FEV 1 : 31±9%pred.) were included in this prospective trial. All patients performed an incremental cycle test to determine the peak work rate (PWR). The PR included daily supervised exercise training sessions (strength- and endurance training). Pre and post PR, biopsies from vastus lasteralis muscle were taken.   Results:   PWR improved significantly during PR (+17Watt [95% CI, 6.3 to 27.7] p  A non-significant but notable increase in the quantity of fibre type I (+6.5%), IIa (+2.2%) and IIx (+2.6%) was detected. Hybrid fibres decreased during PR (type I/IIa: -1.3% [95% CI, -2.21 to -0.39] p   Conclusions:   These preliminary data show that an inpatient 3-week PR is able to exert relevant adaptations in peripheral muscle of COPD patients. This includes an increase in capillarization and an augmented type I myofiber distribution. To confirm these first results, further patients will be investigated.
Partial Anterior vs Partial Posterior Fundoplication Following Transabdominal Esophagocardiomyotomy for Achalasia of the Esophagus
Authors: Ashwin A. Kurian, Neil Bhayani, Ahmed Sharata, Kevin Reavis, Christy M. Dunst, Lee L. Swanström
Journal: JAMA Surgery (2013)

Objectives: To review transabdominal esophagocardiomyotomy (surgical treatment of achalasia) of the esophagus and to compare outcomes of partial anterior vs partial posterior fundoplication.
EXPERIMENTAL STUDIES ON THE BRIDGING HYPOTHESIS OF ANAPHYLAXIS
Authors: Horst Mossmann, Margot Meyer-Delius, Uta Vortisch, Botho Kickhöfen, Dietrich K. Hammer
Journal: The Journal of Experimental Medicine (1974)

The present study has established, that cows suitably immunized with either DNP-edestin (DNP-Ed), di-DNP-gramicidin-J [(DNP)(2)-Gram], respectively, or p-azobenzenearsonate-Ed (ABA-Ed) synthesized and secreted reaginic antibodies (IgE) into colostrum. Whereas ABA-Ed failed to elicit more than a low response, there was however a persistent and increased antibody synthesis between 10 and 56 days after priming with DNP-Ed. Bivalent and multivalent DNP haptens differing in molecular size, degree of substitution, and rigidity were compared for their effectiveness in eliciting Prausnitz-Küstner (P-K) reactions in either newborn colostrum-deprived calves or in those 4 wk of age. The sensitization with reaginic anti-DNP antibody has been accomplished either by feeding colostrum of the immunized dam or by intradermal injection of reaginic serum or colostral whey. It could be demonstrated that equimolar doses of the bivalent alpha,N-(epsilon,N-DNP-aminocaproyl-)-epsilon,N-DNP-L-lysine and the multivalent dinitrophenylated bovine serum albumin were equally effective in eliciting reactions in skin sites provided that a high affinity antibody was used for sensitization. By contrast, the comparatively rigid, bivalent hapten, (DNP)(2)-Gram consistently failed to induce comparable reactions. Furthermore, it was clearly shown that optimal distances of determinant groups on the haptenic molecule are a prerequisite for positive P-K reactions, since alpha,epsilon,N-bis-DNP-lysine failed to induce comparable reactions. Concurrent sensitization of skin sites with reaginic anti-DNP and anti-ABA antibodies provides the final proof that cross-linking of two adjacent reaginic molecules on the mast cell surface by a bivalent hapten is required for effective elicitation of immediate-type reactions. This has been accomplished by utilizing the bivalent epsilon,N-DNP-alpha,N-[(4-hydroxy-3-azobenzenearsonic acid)-phenacetyl]-L-lysine (DNP-ABA) carrying noncross-reactive haptenic groups, which was consistently effective in eliciting P-K reactions in doubly but never in singly sensitized skin sites. It is apparent from the results that equimolar doses of monovalent haptens could completely inhibit the response to DNP-ABA. The present studies finally establish that mast cells of newborn colostrum-deprived calves lack IgE molecules on their surface. Thus, mast cells of newborn calves may be unique, to investigate the molecular mechanisms involved in immediate-type reactions more precisely.
Point: Visceral Adiposity Is Causally Related to Insulin Resistance
Authors: Harold E. Lebovitz, Mary Ann Banerji
Journal: Diabetes Care (2005)

The relationship between obesity and insulin resistance, while well recognized for many years, has nonetheless been confusing since not all obese individuals have insulin resistance (1) and because insulin resistance occurs in individuals who have BMIs that are within the normal or mildly overweight categories (2).

Early attempts to understand the relationships between obesity, type 2 diabetes, and cardiovascular disease focused on the waist-to-hip ratio as a means of distinguishing those individuals who were at increased risk from those who were not (3,4). A high waist-to-hip ratio is a surrogate for masculine distribution of obesity (central obesity). Cross-sectional studies by Kissebah et al. (5) and Krotkiewski et al. (6) in the 1980s demonstrated that hypertension, hypertriglyceridemia, hyperinsulinemia, and glucose intolerance were increased in subjects with a high waist-to-hip ratio. Long-term longitudinal population-based studies of men (13.5 years) and women (12 years) in Gothenburg, Sweden, showed that the waist-to-hip ratio was a predictor of the future development of diabetes, myocardial infarction, angina pectoris, stroke, and death independent of BMI (3,4).

Technology developed in the 1990s, including computer tomography scans and MRI, made it possible to precisely measure specific adipose tissue depots such as total body adipose tissue mass, abdominal subcutaneous adipose tissue mass, visceral adipose tissue mass, and hepatic and intramuscular triglyceride content (7,8). Utilizing those techniques, many studies have examined the relationship between total adipose tissue, abdominal subcutaneous adipose tissue, and visceral adipose tissue mass and insulin resistance, the components of the metabolic syndrome, and the development of type 2 diabetes or clinical cardiovascular events (9–21).

Despite the much smaller size of the visceral adipose tissue depot compared with the total subcutaneous adipose tissue depot or total adiposity, many investigations demonstrated that the visceral adipose tissue mass and not …
Novel Polymorphisms in Promoter Region of ATP Binding Cassette Transporter Gene and Plasma Lipids, Severity, Progression, and Regression of Coronary Atherosclerosis and Response to Therapy
Authors: Silvia Lutucuta, Christie M. Ballantyne, Hesham Elghannam, Antonio M. Gotto, A. J. Marian
Journal: Circulation Research (2001)

Abstract —Identification of mutations in the ATP binding cassette transporter ( ABCA1 ) gene in patients with Tangier disease, who exhibit reduced HDL cholesterol (HDL-C) and apolipoprotein A1 (apoA1) levels and premature coronary atherosclerosis, has led to the hypothesis that common polymorphisms in the ABCA1 gene could determine HDL-C and apoA1 levels and the risk of coronary atherosclerosis in the general population. We sequenced a 660-bp 5′ fragment of the ABCA1 gene in 24 subjects and identified 3 novel polymorphisms: −477C/T, −419A/C, and −320G/C. We developed assays, genotyped 372 participants in the prospective Lipoprotein Coronary Atherosclerosis Study (LCAS), and determined the association of the variants with fasting plasma lipids and indices of quantitative coronary angiograms obtained at baseline and 2.5 years after randomization to fluvastatin or placebo. Distribution of −477C/T and −320G/C genotypes were 127 CC, 171 CT, and 74 TT and 130 GG, 168 GC, and 75 CC, respectively, and were in complete linkage disequilibrium ( P &lt;0.0001). Data for −477C/T are presented. The −419A/C variant was uncommon (present in 1 of 63 subjects). Heterozygous subjects had a modest reduction in HDL-C ( P =0.09) and apoA1 ( P =0.05) levels and a lesser response of apoA1 to treatment with fluvastatin ( P =0.04). The mean number of coronary lesions causing 30% to 75% diameter stenosis was greater in subjects with the TT genotype (3.1±2.1) or CT genotype (2.9±1.9) than in subjects with the CC genotype (2.2±1.8) ( P =0.002). Similarly, compared with subjects with the CC genotype , greater numbers of subjects with the TT or CT genotype had ≥1 coronary lesion ( P =0.001). No association between the genotypes and progression of coronary atherosclerosis or clinical events was detected. We conclude that ABCA1 genotypes are potential risk factors for coronary atherosclerosis in the general population.
Response to Letter Regarding Article, “Optimism, Cynical Hostility, and Incident Coronary Heart Disease and Mortality in the Women’s Health Initiative”
Authors: Hilary A. Tindle, Yue-Fang Chang, Lewis H. Kuller, Greg J. Siegle, Karen A. Matthews, JoAnn E. Manson, Jennifer G. Robinson, Milagros C. Rosal
Journal: Circulation (2010)

We thank Drs Lucchetti and Granero for their commentary on our work 1 on psychological attitudes and mortality and thank the editors for an opportunity to respond.We agree that the biopsychosocial model, 2 which incorporates psychological, religious/spiritual, and social domains, adds critical dimensions to the understanding of each individual patient's health.As Drs Lucchetti and Granero point out, spirituality and religiosity have been related to health in a variety of populations, 3 including the Women's Health Initiative. 4 Although spirituality and religiosity may probe different aspects of human experience, they are often considered together in the literature.The hypothesis that individuals who regularly attend religious services may in turn be more optimistic is a reasonable one, suggesting that the relationship between optimism and all-cause mortality may be mediated by religious attendance.In our published report of 97 253 postmenopausal women participating in the Women's Health Initiative, trait optimism (as measured by the Life Orientation Test-Revised 5 and defined as positive future expectation), trait cynical hostility (as measured by the Cook Medley cynicism subscale 6 and defined as the general mistrust of others), and religious attendance (not at all, 1 to 3 times per month, Ͼ1 time per week) were measured at baseline entry into the study.Optimism, but not cynical hostility, was related to religious attendance.The Spearman correlation between religious attendance and optimism was 0.05 in the full sample.Women scoring in the highest quartile of the Life Orientation Test-Revised ("optimists") were more likely than women scoring in the lowest quartile ("pessimists") to report attending religious services Ͼ1 time per week (47% versus 41%, respectively; PϽ0.001).In contrast, among both women scoring in the highest and women scoring in the lowest quartiles on the cynical hostility questionnaire, 45% reported attending religious services Ͼ1 time per week.When religious attendance was added to the multivariable Cox proportional-hazard models, the adjusted hazard of total mortality over 8 years of follow-up among optimists (compared with pessimists) remained 14% lower (indicating no change from the estimate in our published article).For completeness, we also added religious attendance to the cynical hostility analyses but, as expected, found no changes.In the full models, religious attendance itself was independently related to the outcome of total mortality, as expected from earlier published work. 4In summary, we did not find evidence that religious attendance influenced the relationship between optimism and mortality.
Is internal anal sphincter degeneration associated with lower oesophageal sphincter dysfunction?
Authors: K. Tan, G. Preziosi, C. R. Cohen, A. V. Emmanuel
Journal: Gut (2011)

<h3>Introduction</h3> Internal anal sphincter (IAS) degeneration is the cause of up to 13% of faecal incontinence referrals to a tertiary centre. The authors speculated that IAS degeneration may represent one aspect of a pan-enteric sphincter dysfunction, and investigated lower oesophageal sphincter (LOS) function and gastro-oesophageal reflux symptoms in these patients. <h3>Methods</h3> In 14 consecutive incontinent patients with IAS degeneration (confirmed by endoanal ultrasound and manometry), the authors measured anal sphincter Resting Pressure (RP), LOS pressure and ambulatory pH-metry. None complained of reflux symptoms. Patients were stratified into two groups based on the total percentage time of pH&lt;4: less than 5% (Group A, n=7; 4 females) and more than 5% (Group B, n=7; 4 females). Secondary outcome measures were the Vaizey incontinence scores and gastro-oesophageal disease quality of life (GORD-HRQL-total, plus heartburn and regurgitation subscores). Comparison of these parameters, correlations and linear regressions between primary and secondary outcome measures were performed. <h3>Results</h3> Group B patients were significantly older than Group A patients (70±7 vs 54±15 years, p=0.005), had lower RP (22.8±4.3 vs 38.5±8.2 mm Hg, p=0.007 respectively) and LOS pressure (5.7±2.1 vs 10.7±4.5 mm Hg, p=0.017 respectively). There was no difference in IAS thickness between the 2 groups (1.2±0.3 mm for both, p=0.902). Vaizey incontinence scores were similar in the 2 groups (A=18.1±3.1 vs B=17.3±2.5), while all 3 GORD-HRQL were lower in group A than group B (GORD-HRQL-total 20.7±5.1 vs 49.5±12.4, p=0.001; GORD-HRQL-hb 10±2.7 vs 25.6±9.7, p=0.001 and GORD-HRQL-reg 10.7±3.7 vs 24±3.7, p=0.001) respectively. Correlations and linear regressions showed a significant inverse relationship between RP and GORD-HRQL-reg score (r=−0.844, p&lt;0.001 and β=−0.0997, p=0.007), and RP and IAS thickness (r=−0.844, p&lt;0.001 and β=−1.465, p=0.006). <h3>Conclusion</h3> IAS degeneration in older patients seems to be associated with significant dysfunction of lower oesophageal sphincter. Further morphological and physiological study should determine if a similar pattern of ageing affects smooth muscle in the gastrointestinal tract.
Silibinin Suppresses Growth of Human Prostate Carcinoma PC-3 Orthotopic Xenograft via Activation of Extracellular Signal-Regulated Kinase 1/2 and Inhibition of Signal Transducers and Activators of Transcription Signaling
Authors: Rana P. Singh, Komal Raina, Gagan Deep, Daniel Chan, Rajesh Agarwal
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Silibinin is currently under phase II clinical trial in prostate cancer patients; however, its antitumor effects and mechanisms are not completely understood. Herein, we studied the efficacy and associated mechanisms of silibinin against orthotopically growing advanced human prostate carcinoma PC-3 tumors. Experimental Design: Athymic male mice were orthotopically implanted with PC-3 cells in prostate and 1 week later after surgical recovery were gavaged daily with silibinin (100 mg/kg body weight) for 7 weeks. Results: Silibinin treatment reduced the lower urogenital weight (including tumor, prostate, and seminal vesicle) by 40% (P &amp;lt; 0.05) without any toxicity in mice. Silibinin decreased proliferating cell nuclear antigen expression and proliferating cells (P &amp;lt; 0.001) but increased cleaved caspase-3-positive cells (P &amp;lt; 0.01) and apoptotic cells (P &amp;lt; 0.001) and suppressed tumor microvessel density (P &amp;lt; 0.001) and vascular endothelial growth factor expression (P = 0.02). Decreased levels of cyclin-dependent kinases 2, 4, and 6, CDC2, and cyclins D1, D3, E, and A were observed, indicating an inhibitory effect of silibinin on cell cycle progression. Silibinin showed a tremendous increase in extracellular signal-regulated kinase 1/2 phosphorylation but decreased c-Jun NH2-terminal kinase 1/2 and p38 mitogen-activated protein kinase phosphorylation. A moderate decrease in phosphorylated and total levels of Akt was also noted. A marked inhibitory effect of silibinin on signal transducers and activators of transcription (STAT) 1 (Tyr701), STAT1 (Ser727), STAT3 (Tyr705), STAT3 (Ser727), and STAT5 (Tyr794) phosphorylation together with a decrease in their total levels was also observed. Conclusions: These findings provide evidence for antitumor efficacy of silibinin against orthotopically growing prostate tumor in mice with multitargeted mechanistic insights and support its clinical investigation in prostate cancer.
Experiential and Didactic Aspects of Training in Therapeutic Group Approaches
Authors: MILTON M. BERGER
Journal: American Journal of Psychiatry (1969)

Expertise in leading therapeutic groups requires one's immersion and involvement as a whole person. The integrated mixture of the experiential and didactic in training programs may allow more group leaders to function humanistically as well as scientifically, the author believes. He reviews the work in the field and describes the program at the New York State Psychiatric Institute, where the experiential approach is being successfully incorporated into the training program.
Acetaldehyde selectively stimulates collagen production in cultured rat liver fat-storing cells but not in hepatocytes
Authors: Han Moshage, Alessandro Casini, Charles S. Lieber
Journal: Hepatology (1990)

Hepatocytes and fat-storing cells have been implicated in the production of collagen, under both normal and pathological conditions. In this study, short-term primary cultures of rat hepatocytes, maintained in a serum-free, hormonally defined medium without dexamethasone and cultured on a fibronectin-collagen type IV substratum, were used. Primary and passage 1 and 2 cultures of fat-storing cells maintained on tissue culture plastic were also studied. Hepatocytes produced significant amounts of collagen type III, but formation of collagen type I was not detectable. Laminin and collagen type IV production were very low. Hepatocytes maintained their ability to metabolize ethanol (at levels comparable to those observed at 2 hr) for at least 48 hr after plating and this metabolism was inhibited 86% to 95% by 4-methylpyrazole (1 mmol/L). Neither ethanol (50 mmol/L) nor acetaldehyde (175 mumol/L, initial concentration) had any effect on the production of collagen type III or laminin. Fat-storing cells (95% to 100% desmin-positive) produced significant amounts of both type I and type III collagen. Production of collagen type IV and laminin was very low. Metabolism of ethanol by these cultures was not detected. Addition of ethanol had no effect on collagen or laminin production in fat-storing cells. In contrast, acetaldehyde significantly increased the production of collagen type I, but did not alter the production of collagen type III, IV or laminin. Incorporation of 3H-proline into total protein was not affected by addition of ethanol or acetaldehyde to fat-storing cells or hepatocytes. Exposure of fat-storing cells to ethanol or acetaldehyde did not change 3H-collagen degrading activity in the media.(ABSTRACT TRUNCATED AT 250 WORDS)
Influence of translation efficiency of homologous viral proteins on the endogenous presentation of CD8+ T cell epitopes
Authors: Judy Tellam, Mark H. Fogg, Michael Rist, Geoff Connolly, David Tscharke, Natasha Webb, Lea Heslop, Fred Wang, Rajiv Khanna
Journal: The Journal of Experimental Medicine (2007)

A significant proportion of endogenously processed CD8+ T cell epitopes are derived from newly synthesized proteins and rapidly degrading polypeptides (RDPs). It has been hypothesized that the generation of rapidly degrading polypeptides and CD8+ T cell epitopes from these RDP precursors may be influenced by the efficiency of protein translation. Here we address this hypothesis by using the Epstein-Barr virus–encoded nuclear antigen 1 protein (EBNA1), with or without its internal glycine-alanine repeat sequence (EBNA1 and EBNA1ΔGA, respectively), which display distinct differences in translation efficiency. We demonstrate that RDPs constitute a significant proportion of newly synthesized EBNA1 and EBNA1ΔGA and that the levels of RDPs produced by each of these proteins directly correlate with the translation efficiency of either EBNA1 or EBNA1ΔGA. As a consequence, a higher number of major histocompatibility complex–peptide complexes can be detected on the surface of cells expressing EBNA1ΔGA, and these cells are more efficiently recognized by virus-specific cytotoxic T lymphocytes compared to the full-length EBNA1. More importantly, we also demonstrate that the endogenous processing of these CD8+ T cell epitopes is predominantly determined by the rate at which the RDPs are generated rather than the intracellular turnover of these proteins.
Transactivation of the PPAR-Responsive Enhancer Module in Chemopreventive Glutathione <b> <i>S</i> </b>-Transferase Gene by the Peroxisome Proliferator-Activated Receptor-γ and Retinoid X Receptor Heterodimer
Authors: Eun Young Park, Il Je Cho, Sang Geon Kim
Journal: Cancer Research (2004)

Abstract Cancer chemopreventive agents transcriptionally induce glutathione S-transferase (GST), which can protect cells from chemical-induced carcinogenesis. Activation of either NF-E2-related factor-2 (Nrf2) or the CCAAT/enhancer binding protein-β (C/EBPβ) contributes to GST induction. Peroxisome proliferator-activated receptor-γ (PPARγ) and the retinoic acid X receptor (RXR) play roles in regulating cell differentiation and chemoprevention. This study examined GSTA2 gene induction by the PPARγ activator and 9-cis-retinoic acid (RA), a RXR ligand, and investigated the molecular basis of PPAR-RXR-mediated GSTA2 induction in the H4IIE hepatocytes. Either 15-deoxy-δ (12, 14)-prostaglandin J2 (PGJ2) or RA induced GSTA2 with Nrf2 and C/EBPβ activation. When compared with PGJ2 or RA alone, PGJ2 + RA enhanced GSTA2 induction, with increases in Nrf2 and C/EBPβ activation. PGJ2 + RA increased the luciferase reporter gene activity in the cells transfected with the −1.65-kb flanking region of the GSTA2 gene. Thiazolidinedione PPARγ agonists, troglitazone, rosiglitazone, and pioglitazone, in combination with RA, potentiated GSTA2 induction, confirming that the activation of the PPARγ and RXR heterodimer contributed to GSTA2 expression. Deletion of the antioxidant response element- or C/EBP-binding sites or the overexpression of dominant-negative mutant of C/EBP abolished the reporter gene expression. PGJ2 + RA increased the binding of the PPARγ − RXR heterodimer to the putative PPAR-response elements (PPREs) in the GSTA2 promoter. Specific mutations of these multiple PPRE sites resulted in the complete loss of its responsiveness to PGJ2 + RA, which suggests that these binding sites function as a PPRE-responsive enhancer module (PPREM). Transactivation of PPREM by the PPARγ − RXR heterodimer was verified by the effective GSTA2 induction in the cells treated with PGJ2 + RA after transfecting them with the plasmids encoding PPARγ1 and RXRα. In conclusion, the PPARγ − RXR heterodimer promotes GSTA2 induction by activating PPREM in the GSTA2 gene, as well as inducing Nrf2 and C/EBPβ activation.