tbuckley/cabot-search huggingface dataset:
Skeletal muscle adaptation to endurance training in patients with chronic obstructive pulmonary disease.
Authors: F Maltais, P LeBlanc, C Simard, J Jobin, C Bérubé, J Bruneau, L Carrier, R Belleau
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

The purpose of this study was to evaluate the physiologic responses to endurance training in patients with moderate to severe airflow obstruction by specifically looking at changes in skeletal muscle enzymatic activities. Eleven patients (age = 65 +/- 7 yr, mean +/- SD, FEV1 = 36 +/- 11% of predicted value, range = 24 to 54%) were evaluated before and after an endurance training program. Each evaluation included a percutaneous biopsy of the vastus lateralis and a stepwise exercise test on an ergocycle up to his/her maximal capacity. VE, VO2, VcO2, and serial arterial lactic acid concentration were measured during the exercise test. The activity of two oxidative enzymes, citrate synthase (CS) and 3-hydroxyacyl-CoA dehydrogenase (HADH), and of three glycolytic enzymes, lactate dehydrogenase, hexokinase, and phosphofructokinase was determined. The training consisted of 30-min exercise sessions on a calibrated ergocycle, 3 times a week for 12 wk. The aerobic capacity was severely reduced at baseline (VO2max = 54 +/- 12% of predicted) and increased by 14% after training (p < 0.05). For an identical exercise workload, there was a significant reduction in VE (34.5 +/- 10.0 versus 31.9 +/- 9.0 L/min, p < 0.05) and in arterial lactic acid concentration (3.4 +/- 1.3 versus 2.8 +/- 0.9 mmol/L, p < 0.01) after training. The lactate threshold also increased after training (p < 0.01) while the activity of the three glycolytic enzymes was similar at the two evaluations. In contrast, the activity of CS and HADH increased significantly after training (22.3 +/- 3.5 versus 25.8 +/- 3.8 mumol/min/g muscle for CS, p < 0.05, and 5.5 +/- 2.9 versus 7.7 +/- 2.5 mumol/min/g for HADH, p < 0.01). A significant inverse relationship was found between the percent changes in the activity of CS and HADH, and the percent changes in arterial lactic acid during exercise (p = 0.01). We conclude that endurance training can reduce exercise-induced lactic acidosis and improve skeletal muscle oxidative capacity in patients with moderate to severe chronic obstructive pulmonary disease (COPD).
National Trends in the Treatment of Attention Deficit Hyperactivity Disorder
Authors: Mark Olfson, Marc J. Gameroff, Steven C. Marcus, Peter S. Jensen
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: Nationally representative descriptive data were presented regarding recent trends in the outpatient treatment of attention deficit hyperactivity disorder (ADHD) in children. METHOD: Service use data were analyzed in children ages 3 to 18 years from two nationally representative surveys of the U.S. general population, the 1987 National Medical Expenditure Survey, and the 1997 Medical Expenditure Panel Survey. Trends in the rates of treatment for ADHD were presented by age, gender, race, family income, and health insurance status. Trends in ADHD treatment were also determined by annual numbers of visits, use of pharmacotherapies, and types of health care professionals. RESULTS: The rate of outpatient treatment for ADHD increased from 0.9 per 100 children in 1987 to 3.4 per 100 children in 1997. Significant increases in the rates of treatment for ADHD were evident across nearly all sociodemographic groups, with the largest increases among children from poor, near-poor, and low-income families and children ages 12 to 18. Among children who received treatment for ADHD, there was a significant decrease in the number of treatment visits but an increase in the number of stimulant prescriptions between 1987 and 1997. CONCLUSIONS: During the decade, there was a marked and broad expansion in access to treatment of children with ADHD but a decline in intensity of treatment, as measured by number of visits. These changes occurred during a period of expanding access to special education services, growth of managed behavioral healthcare, and increased public acceptance of effective psychotropic medications.
A tale of two cities: effects of air pollution on hospital admissions in Hong Kong and London compared.
Authors: Chit-Ming Wong, Richard W Atkinson, H Ross Anderson, Anthony Johnson Hedley, Stefan Ma, Patsy Yuen-Kwan Chau, Tai-Hing Lam
Journal: Environmental Health Perspectives (2002)

The causal interpretation of reported associations between daily air pollution and daily admissions requires consideration of residual confounding, correlation between pollutants, and effect modification. If results obtained in Hong Kong and London--which differ in climate, lifestyle, and many other respects--were similar, a causal association would be supported. We used identical statistical methods for the analysis in each city. Associations between daily admissions and pollutant levels were estimated using Poisson regression. Nonparametric smoothing methods were used to model seasonality and the nonlinear dependence of admissions on temperature, humidity, and influenza admissions. For respiratory admissions (> or = 65 years of age), significant positive associations were observed with particulate matter < 10 microm in aerodynamic diameter (PM(10), nitrogen dioxide, sulfur dioxide, and ozone in both cities. These associations tended to be stronger at shorter lags in Hong Kong and at longer lags in London. Associations were stronger in the cool season in Hong Kong and in the warm season in London, periods during which levels of humidity are at their lowest in each city. For cardiac admissions (all ages) in both cities, significant positive associations were observed for PM(10), NO(2), and SO(2) with similar lag patterns. Associations tended to be stronger in the cool season. The associations with NO(2) and SO(2) were the most robust in two-pollutant models. Patterns of association for pollutants with ischemic heart disease were similar in the two cities. The associations between O(3) and cardiac admissions were negative in London but positive in Hong Kong. We conclude that air pollution has remarkably similar associations with daily cardiorespiratory admissions in both cities, in spite of considerable differences between cities in social, lifestyle, and environmental factors. The results strengthen the argument that air pollution causes detrimental short-term health effects.
Genome-wide identification and functional analysis of Apobec-1-mediated C-to-U RNA editing in mouse small intestine and liver
Authors: Valerie Blanc, Eddie Park, Sabine Schaefer, Melanie Miller, Yiing Lin, Susan Kennedy, Anja M Billing, Hisham Hamidane, Johannes Graumann, Ali Mortazavi, Joseph H Nadeau, Nicholas O Davidson
Journal: Genome biology (2014)

RNA editing encompasses a post-transcriptional process in which the genomically templated sequence is enzymatically altered and introduces a modified base into the edited transcript. Mammalian C-to-U RNA editing represents a distinct subtype of base modification, whose prototype is intestinal apolipoprotein B mRNA, mediated by the catalytic deaminase Apobec-1. However, the genome-wide identification, tissue-specificity and functional implications of Apobec-1-mediated C-to-U RNA editing remain incompletely explored. Deep sequencing, data filtering and Sanger-sequence validation of intestinal and hepatic RNA from wild-type and Apobec-1-deficient mice revealed 56 novel editing sites in 54 intestinal mRNAs and 22 novel sites in 17 liver mRNAs, all within 3′ untranslated regions. Eleven of 17 liver RNAs shared editing sites with intestinal RNAs, while 6 sites are unique to liver. Changes in RNA editing lead to corresponding changes in intestinal mRNA and protein levels for 11 genes. Analysis of RNA editing in vivo following tissue-specific Apobec-1 adenoviral or transgenic Apobec-1 overexpression reveals that a subset of targets identified in wild-type mice are restored in Apobec-1-deficient mouse intestine and liver following Apobec-1 rescue. We find distinctive polysome profiles for several RNA editing targets and demonstrate novel exonic editing sites in nuclear preparations from intestine but not hepatic apolipoprotein B RNA. RNA editing is validated using cell-free extracts from wild-type but not Apobec-1-deficient mice, demonstrating that Apobec-1 is required. These studies define selective, tissue-specific targets of Apobec-1-dependent RNA editing and show the functional consequences of editing are both transcript- and tissue-specific.
Identification of Susceptibility Loci in <i>IL6</i>, <i>RPS9</i>/<i>LILRB3</i>, and an Intergenic Locus on Chromosome 21q22 in Takayasu Arteritis in a Genome‐Wide Association Study
Authors: Paul A. Renauer, Guher Saruhan‐Direskeneli, Patrick Coit, Adam Adler, Kenan Aksu, Gokhan Keser, Fatma Alibaz‐Oner, Sibel Z. Aydin, Sevil Kamali, Murat Inanc, Simon Carette, David Cuthbertson, Gary S. Hoffman, Servet Akar, Fatos Onen, Nurullah Akkoc, Nader A. Khalidi, Curry Koening, Omer Karadag, Sedat Kiraz, Carol A. Langford, Kathleen Maksimowicz‐McKinnon, Carol A. McAlear, Zeynep Ozbalkan, Askin Ates, Yasar Karaaslan, Nursen Duzgun, Paul A. Monach, Huseyin T. E. Ozer, Eren Erken, Mehmet A. Ozturk, Ayten Yazici, Ayse Cefle, Ahmet Mesut Onat, Bunyamin Kisacik, Christian Pagnoux, Timucin Kasifoglu, Emire Seyahi, Izzet Fresko, Philip Seo, Antoine G. Sreih, Kenneth J. Warrington, Steven R. Ytterberg, Veli Cobankara, Deborah S. Cunninghame‐Graham, Timothy J. Vyse, Omer N. Pamuk, S. Ercan Tunc, Ediz Dalkilic, Muge Bicakcigil, Sibel P. Yentur, Jonathan D. Wren, Peter A. Merkel, Haner Direskeneli, Amr H. Sawalha
Journal: Arthritis & Rheumatology (2015)

Objective Takayasu arteritis is a rare large vessel vasculitis with incompletely understood etiology. This study was undertaken to perform the first unbiased genome‐wide association analysis of Takayasu arteritis. Methods Two independent cohorts of patients with Takayasu arteritis from Turkey and North America were included in our study. The Turkish cohort consisted of 559 patients and 489 controls, and the North American cohort consisted of 134 patients and 1,047 controls of European ancestry. Genotyping was performed using the Omni1‐Quad and Omni2.5 genotyping arrays. Genotyping data were subjected to rigorous quality control measures and subsequently analyzed to discover genetic susceptibility loci for Takayasu arteritis. Results We identified genetic susceptibility loci for Takayasu arteritis with a genome‐wide level of significance in IL6 (rs2069837) (odds ratio [OR] 2.07, P = 6.70 × 10 −9 ), RPS9 / LILRB3 (rs11666543) (OR 1.65, P = 2.34 × 10 −8 ), and an intergenic locus on chromosome 21q22 (rs2836878) (OR 1.79, P = 3.62 × 10 −10 ). The genetic susceptibility locus in RPS9 / LILRB3 lies within the leukocyte receptor complex gene cluster on chromosome 19q13.4, and the disease risk variant in this locus correlates with reduced expression of multiple genes including the inhibitory leukocyte immunoglobulin‐like receptor gene LILRB3 ( P = 2.29 × 10 −8 ). In addition, we identified candidate susceptibility genes with suggestive levels of association ( P &lt; 1 × 10 −5 ) with Takayasu arteritis, including PCSK5, LILRA3, PPM1G/NRBP1 , and PTK2B . Conclusion Our findings indicate novel genetic susceptibility loci for Takayasu arteritis and uncover potentially important aspects of the pathophysiology of this form of vasculitis.
Visceral Adipose Tissue Inflammation Accelerates Atherosclerosis in Apolipoprotein E–Deficient Mice
Authors: Miina K. Öhman, Yuechun Shen, Chinyere I. Obimba, Andrew P. Wright, Mark Warnock, Daniel A. Lawrence, Daniel T. Eitzman
Journal: Circulation (2008)

Background— Fat inflammation may play an important role in comorbidities associated with obesity such as atherosclerosis. Methods and Results— To first establish feasibility of fat transplantation, epididymal fat pads were harvested from wild-type C57BL/6J mice and transplanted into leptin-deficient ( Lep ob/ob ) mice. Fat transplantation produced physiological leptin levels and prevented obesity and infertility in Lep ob/ob mice. However, the transplanted fat depots were associated with chronically increased macrophage infiltration with characteristics identical to those observed in fat harvested from obese animals. The inflammation in transplanted adipose depots was regulated by the same factors that have been implicated in endogenous fat inflammation such as monocyte chemoattractant protein-1. To determine whether this inflamed adipose depot could affect vascular disease in mice, epididymal fat depots were transplanted into atherosclerosis-prone apolipoprotein E–deficient ApoE −/− mice. Plasma from ApoE −/− mice receiving fat transplants contained increased leptin, resistin, and monocyte chemoattractant protein-1 compared with plasma from sham-operated ApoE −/− mice. Furthermore, mice transplanted with visceral fat developed significantly more atherosclerosis compared with sham-operated animals, whereas transplants with subcutaneous fat did not affect atherosclerosis despite a similar degree of fat inflammation. Treatment of transplanted ApoE −/− mice with pioglitazone decreased macrophage content of the transplanted visceral fat pad and reduced plasma monocyte chemoattractant protein-1. Importantly, pioglitazone also reduced atherosclerosis triggered by inflammatory visceral fat but had no protective effect on atherosclerosis in the absence of the visceral fat transplantation. Conclusions— Our results indicate that visceral adipose-related inflammation accelerates atherosclerosis in mice. Drugs such as thiazolidinediones might be a useful strategy to specifically attenuate the vascular disease induced by visceral inflammatory fat.
A modified prebind engagement process reduces biomechanical loading on front row players during scrummaging: a cross-sectional study of 11 elite teams
Authors: Dario Cazzola, Ezio Preatoni, Keith A Stokes, Michael E England, Grant Trewartha
Journal: British Journal of Sports Medicine (2014)

Biomechanical studies of the rugby union scrum have typically been conducted using instrumented scrum machines, but a large-scale biomechanical analysis of live contested scrummaging is lacking. We investigated whether the biomechanical loading experienced by professional front row players during the engagement phase of live contested rugby scrums could be reduced using a modified engagement procedure.Eleven professional teams (22 forward packs) performed repeated scrum trials for each of the three engagement techniques, outdoors, on natural turf. The engagement processes were the 2011/2012 (referee calls crouch-touch-pause-engage), 2012/2013 (referee calls crouch-touch-set) and 2013/2014 (props prebind with the opposition prior to the 'Set' command; PreBind) variants. Forces were estimated by pressure sensors on the shoulders of the front row players of one forward pack. Inertial Measurement Units were placed on an upper spine cervical landmark (C7) of the six front row players to record accelerations. Players' motion was captured by multiple video cameras from three viewing perspectives and analysed in transverse and sagittal planes of motion.The PreBind technique reduced biomechanical loading in comparison with the other engagement techniques, with engagement speed, peak forces and peak accelerations of upper spine landmarks reduced by approximately 20%. There were no significant differences between techniques in terms of body kinematics and average force during the sustained push phase.Using a scrum engagement process which involves binding with the opposition prior to the engagement reduces the stresses acting on players and therefore may represent a possible improvement for players' safety.
Glia Maturation Factor-γ Is Preferentially Expressed in Microvascular Endothelial and Inflammatory Cells and Modulates Actin Cytoskeleton Reorganization
Authors: Koji Ikeda, Ramendra K. Kundu, Shoko Ikeda, Miyuki Kobara, Hiroaki Matsubara, Thomas Quertermous
Journal: Circulation Research (2006)

Actin cytoskeleton reorganization is a fundamental process for actin-based cellular functions such as cytokinesis, phagocytosis, and chemotaxis. Regulating actin cytoskeleton reorganization is therefore an attractive approach to control endothelial and inflammatory cells function and to treat cardiovascular diseases. Here, we identified glia maturation factor-gamma (GMFG) as a novel factor in actin cytoskeleton reorganization and is expressed preferentially in microvascular endothelial and inflammatory cells. During mouse embryogenesis, GMFG was expressed predominantly in blood islands of the yolk sac, where endothelial and hematopoietic cells develop simultaneously. In endothelial cells, GMFG was colocalized with F-actin in membrane ruffles and was associated with F-actin assessed by actin co-sedimentation assay. Interestingly, GMFG was phosphorylated at N-terminal serine, and its phosphorylation was enhanced by coexpression of dominant active Rac1 and Cdc42. Furthermore, a pseudophosphorylated form of GMFG (GMFG-S2E) demonstrated higher association with F-actin. Stable expression of GMFG-S2E remarkably enhanced stimulus-responsive lamellipodia and subsequent membrane ruffle formation in HeLa cells presumably through its interaction with Arp2/3 complex. Expression of GMFG enhanced actin-based cellular functions such as migration and tube-formation in endothelial cells. Moreover, we found that GMFG expression was significantly increased in a cardiac ischemia/reperfusion model where inflammation and angiogenesis take place actively. Taken together, our findings define a novel pathway in the regulation of actin-based cellular functions. Regulating GMFG function may provide a novel approach to modulate the pathophysiology of cardiovascular diseases.
The Aging Brain
Authors: Bruce A. Yankner, Tao Lu, Patrick Loerch
Journal: Annual Review of Pathology Mechanisms of Disease (2008)

Aging is accompanied by cognitive decline in a major segment of the population and is the primary risk factor for Alzheimer's disease and other prevalent neurodegenerative disorders. Despite this central role in disease pathogenesis and morbidity, the aging of the brain has not been well understood at a molecular level. This review seeks to integrate what is known about age-related cognitive and neuroanatomical changes with recent advances in understanding basic molecular mechanisms that underlie aging. An important issue is how normal brain aging transitions to pathological aging, giving rise to neurodegenerative disorders. Toxic protein aggregates have been identified as potential contributory factors, including amyloid beta-protein in Alzheimer's disease, tau in frontotemporal dementia, and alpha-synuclein in Parkinson's disease. However, current models of pathogenesis do not explain the origin of the common sporadic forms of these diseases or address the critical nexus between aging and disease. This review discusses potential approaches to unifying the systems biology of the aging brain with the pathogenesis of neurodegeneration.
Fourier Analysis of Left Ventricular Performance
Authors: FRANCIS L. ABEL
Journal: Circulation Research (1971)

Fourier analysis has been applied to simultaneously obtained ventricular pressure, ascending aortic pressure, and aortic flow in the closed- and open- chest dog and during infusion with isoproterenol, norepinephrine, and phenylephrine. Partial measurements were also obtained from a sheep and a primate. Impedance moduli and phases were calculated from the ventricular (forcing) and aortic (input) side of the aortic valve and compared. Forcing impedance was similar in form but larger than input impedance, and the phase became positive earlier. Ventricular and aortic powers were calculated and expressed as pressure power, kinetic energy power, and reactive power, along with their harmonic distributions. Mean pressure represented 80 to 91% of total load power but only 20 to 51% of total ventricular power. Calculated efficiency varied from 35% with isoproterenol infusion to 100% with norepinephrine, phenylephrine, and open-chest states. Control efficiency was 78%. The concept of impedance matching was investigated; maximal efficiency occurred with optimal matching. Internal resistance was shown to represent an easily measurable quantity which also partially corresponds to the more complex impedance measurement.
Induction of neonatal tolerance to H-2k in B6 mice does not allow the emergence of T cells specific for H-2k plus vaccinia virus.
Authors: D H Schwartz, P C Doherty
Journal: The Journal of Experimental Medicine (1982)

Thymocytes and spleen cells from C57BL/6 mice (H-2b) neonatally tolerized to H-2k alloantigens do not generate an anti-vaccinia response restricted to H-2Kk when adoptively transferred to appropriate irradiated hosts. This is in sharp contrast to the case for negatively selected C57BL/6 spleen cells acutely depleted of alloreactivity. No evidence for suppression was found in cell mixture experiments. We have shown elsewhere that our neonatally tolerized animals have a centrally induced delection-type tolerance in the absence of obvious suppression.2 We now suggest that in the neonatally tolerized mouse, chronic, central delection of anti-H-2k clones during early T cell ontogeny eliminates the major source of cells able to give rise, via somatic mutation and expansion, to anti-H-2Kk + vaccinia specific cytotoxic T lymphocyte precursors (CTL-P) in the adult. A similar mechanism may operate in the (k + b) leads to b chimera; however, the presence of H-2kxb accessory and presenting cells may permit the eventual generation (via cross-stimulation) of an H-2k-restricted vaccinia-specific repertoire. This would account for our observation of such "aberrant recognition" CTL-P emerging in the spleens of older (k x b) leads to b chimeras.
Interpretation of pleural biopsy specimens and aspirates with the immunoperoxidase technique.
Authors: A Herbert, P J Gallagher
Journal: Thorax (1982)

In pleural biopsy specimens and histological sections from the fibrin clots of pleural fluid aspirates it may be difficult to distinguish reactive mesothelial cells from malignant mesothelial cells and metastatic carcinoma. Reactive pleurisy with effusion is usually associated with loss of cohesion and exfoliation of mesothelial cells, which is consistent with the hypothesis that they act as facultative histiocytes. A series of biopsy specimens and sections of clots from benign and malignant pleural effusions have been stained by the immunoperoxidase technique for the histiocytic markers alpha 1-antitrypsin, alpha 1-antichymotrypsin, and lysozyme (muramidase). Eight cases of mesothelioma were included. Mesothelial cells when seen as a monolayer lining the pleural surface were negative. Reactive mesothelial cells, usually seen as exfoliated cells, were consistently strongly positive for alpha 1-antichymotrypsin and more variably for alpha 1-antitrypsin and lysozyme. Malignant cells, whether from carcinoma or from mesothelioma, were usually but not always negative. Consequently immunohistochemical staining for alpha 1-antichymotrypsin is often helpful in distinguishing reactive mesothelial cells from malignant cells.