tbuckley/cabot-search huggingface dataset:
Hepatic hemodynamics and oxygen consumption in alcoholic fatty liver assessed by organ-reflectance spectrophotometry and the hydrogen clearance method
Authors: Akinori Kasahara, Norio Hayashi, Kazuhei Kurosawa, Yutaka Sasaki, Nobuhiro Sato, Takenobu Kamada
Journal: Hepatology (1986)

Hepatic blood flow and estimated hepatic oxygen consumption were studied in rats treated chronically with ethanol by organ-reflectance spectrophotometry and the hydrogen clearance method. In the withdrawal state from ethanol, the concentration of hemoglobin in the hepatic tissue (delta Er569-650), the estimated hepatic oxygen consumption (estimated VO2) and the regional liver blood flow decreased significantly in rats treated chronically with ethanol in comparison with their controls. On the other hand, there was no significant difference in the estimated oxygen saturation of the hepatic blood hemoglobin (estimated SO2) between both groups. That is, an increase in oxygen extraction, which was exhibited by a decrease in the estimated SO2, did not occur in rats treated chronically with ethanol in spite of a decrease in blood supply. Thus, in the withdrawal state from ethanol, both oxygen delivery to the liver and oxygen utilization in the liver were disturbed at the stage of alcoholic fatty liver.
Acute Hypoglycemia in Humans Causes Attentional Dysfunction While Nonverbal Intelligence Is Preserved
Authors: Vincent McAulay, Ian J. Deary, Stewart C. Ferguson, Brian M. Frier
Journal: Diabetes Care (2001)

Experimentally induced hypoglycemia in humans causes progressive but reversible cognitive dysfunction, but it is not known to what extent neuropsychological tests index abilities of cognitive functioning that are important in everyday life. This study examines the effects of acute insulin-induced hypoglycemia on attention and intelligence in nondiabetic humans.A hyperinsulinemic glucose clamp was used to achieve controlled euglycemia (4.50 [0.22] mmol/l) and hypoglycemia (blood glucose 2.59 [0.19] mmol/l) in 20 healthy volunteers. Subjects were studied on two occasions in a counterbalanced order. During each study condition, subjects completed parallel tests of cognitive function. Cognitive function was assessed by the Test of Everyday Attention and Raven's Progressive Matrices.Hypoglycemia induced a significant deterioration in tests sensitive to both visual and auditory selective attention. During hypoglycemia, attentional flexibility deteriorated and speed of information processing was delayed. Sustained attention was preserved and intelligence scores did not deteriorate during hypoglycemia.During hypoglycemia, a significant deterioration occurs in attentional abilities, whereas fluid intelligence is preserved. On the basis of these results, it can be surmised that many complex attention tasks relevant to everyday life are impaired during moderate hypoglycemia.
Atypical Developmental Patterns of Brain Chemistry in Children With Autism Spectrum Disorder
Authors: Neva M. Corrigan, Dennis W. W. Shaw, Annette M. Estes, Todd L. Richards, Jeff Munson, Seth D. Friedman, Geraldine Dawson, Alan A. Artru, Stephen R. Dager
Journal: JAMA Psychiatry (2013)

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with symptoms emerging during early childhood. The pathophysiology underlying the disorder remains incompletely understood.To examine cross-sectional and longitudinal patterns of brain chemical concentrations in children with ASD or idiopathic developmental delay (DD) from 3 different age points, beginning early in the clinical course.Proton magnetic resonance spectroscopic imaging data were acquired longitudinally for children with ASD or DD, and primarily cross-sectionally for children with typical development (TD), at 3 to 4, 6 to 7, and 9 to 10 years of age.Recruitment, diagnostic assessments, and magnetic resonance imaging were performed at the University of Washington in Seattle.Seventy-three children (45 with ASD, 14 with DD, and 14 with TD) at 3 to 4 years of age; 69 children (35 with ASD, 14 with DD, and 20 with TD) at 6 to 7 years of age; and 77 children (29 with ASD, 15 with DD, and 33 with TD) at 9 to 10 years of age.Concentrations of N-acetylaspartate (NAA), choline (Cho), creatine (Cr), myo-inositol (mI), and glutamine plus glutamate (Glx) in cerebral gray matter (GM) and white matter (WM) at 3 to 4, 6 to 7, and 9 to 10 years of age, and calculation of rates of change of these chemicals between 3 and 10 years of age.At 3 to 4 years of age, the ASD group exhibited lower NAA, Cho, and Cr concentrations than did the TD group in both GM and WM, alterations that largely were not observed at 9 to 10 years of age. The DD group exhibited reduced GM and WM NAA concentrations at 3 to 4 years of age; GM NAA concentrations remained reduced at 9 to 10 years of age compared with the TD group. There were distinct differences between the ASD and DD groups in the rates of GM NAA, Cho, and Cr changes between 3 and 10 years of age.The GM chemical changes between 3 and 10 years of age differentiated the children with ASD from those with DD. Most notably, a dynamic reversal of GM NAA reductions was observed in the children with ASD. By contrast, persistent GM NAA reductions in the children with DD suggest a different, more static, underlying developmental process.
MODIFICATION OF HOST RESPONSES TO BACTERIAL ENDOTOXINS
Authors: Dennis W. Watson, Yoon Berm Kim
Journal: The Journal of Experimental Medicine (1963)

Evidence is presented suggesting that the apparent non-specificity of pyrogenic tolerance observed with Gram-negative bacterial endotoxins is due to related antigenic determinants associated with the macromolecular toxins. This is based on results obtained in rabbits from pyrogenic cross-tolerance tests with selected endotoxins. In these tests, purified endotoxins from Escherichia coli (COO8) and Chromobacterium violaceum (CV) gave results one might expect with non-reciprocal cross-reacting antigens in classical immune systems. Additional evidence for an immune mechanism in tolerance is suggested by the highly significant anamnestic response observed. Lipid A, a toxic derivative of the purified COO8 endotoxin, failed to induce pyrogenic tolerance against the parent toxin. These results are explained by assuming that endotoxins have two interdependent activities associated with different portions of the macromolecule; one is assumed to be responsible for the primary toxicity, and the other is involved in secondary toxicity. The latter is dependent on the hypersensitive state of the host. Additional evidence for the role of hypersensitivity in secondary toxicity is based on the observation that adult rabbits are highly sensitive to the pyrogenic, lethal, and skin-reacting activities of endotoxin in contrast to young animals which are more resistant to all of these attributes of toxicity. In adults, the host responses to pyrogenicity, lethality, and skin reactivity could be partially inhibited by the early exposure of the animals to massive doses of endotoxin equivalent to a LD(50). The pyrogenic tolerance shown in these animals was specific indicating that the inhibition of the hypersusceptibility to endotoxin involved an immunological mechanism. A mechanism of endotoxin tolerance is proposed and discussed based on the induction of specific antibodies capable of assisting the RES in the clearance and destruction of endotoxin. It is suggested that the present inconsistencies relative to the chemical nature and biological activities of endotoxins might be explained on the basis of these two activities and the failure to recognize the importance of the immunological state of the host in which the toxins are tested.
Effects of perfluorochemical hemodilution on coronary blood flow distribution in dogs.
Authors: J G Kingma, J R Rouleau, J Magrina, G R Dagenais
Journal: Circulation (1988)

To determine the effect of perfluorocarbon (PFC) hemodilution on myocardial vessel capacity to autoregulate, circumflex coronary artery pressure-flow relations were studied in anesthetized dogs under three conditions: maximal vasodilatation before and after PFC; autoregulation before and after PFC with 100% oxygen supplemented with room air ventilation, and autoregulation with PFC hemodilution during either room air or 100% oxygen supplemented with room air ventilation. During coronary vasodilatation, PFC did not modify coronary conductance or zero-flow pressure. During autoregulation after PFC, the lower pressure limit of the autoregulatory pressure-flow relation was shifted leftward. This leftward shift occurred because endocardial blood flow was maintained at a lower coronary perfusion pressure with PFC while epicardial blood flow was unchanged. Endocardial blood flow was also preserved at 50% of control blood flow levels as evidenced by the higher endocardial-epicardial blood flow ratio with PFC. After PFC with 100% oxygen supplemented with room air ventilation, oxygen transport increased significantly when coronary perfusion pressure was below the lower pressure limit; the effect was most prominent in the endocardial tissue layer. Thus, PFC shifts the lower pressure limit to the left because of the increased ability of the endocardial vessel to autoregulate. Consequently, PFC can be considered a useful intervention for improving endocardial oxygen transport at low coronary perfusion pressures.
The role of arterial baroreceptors in mediating the cardiovascular response to a cardiac glycoside in conscious dogs.
Authors: R J McRitchie, S F Vatner
Journal: Circulation Research (1976)

To determine the role of the arterial baroreceptor reflex in mediating the cardiovascular response to a cardiac glycoside, we examined the effects of ouabain (G-strophanthin), 17.5 mug/kg, iv, on direct and continuous measurements of left ventricular diameters, pressures, velocity of shortening, (dP/dt)/P, arterial pressure, cardiac output, and total peripheral resistance. These studies were conducted on healthy conscious dogs before and after total arterial baroreceptor denervation (TABD). Maximal pressor effects were observed in the first 3-5 minutes; mean arterial pressure increased by 11 +/- 1 mm Hg in normal dogs compared to 33 +/- 4 mm Hg in denervated dogs. In intact dogs at this time heart rate decreased by 18 +/- 2 beats/min and cardiac output fell by 18 +/- 3%; these values gradually returned toward control over 15-30 minutes. When heart rate was kept constant, cardiac output did not fall after injection of ouabain. In contrast, heart rate and cardiac output did not change significantly after ouabain in dogs with TABD. The maximal effects on the contractile state of the heart occurred between 15-30 minutes and were similar in both groups. Arterial baroreceptor reflexes appear to be responsible for the reduction in heart rate and cardiac output caused by administration of ouabain to the intact dog. They exert an important buffering action on the vasopressor effect but a less important action on the inotropic response.
NADH Oxidase Activity of Rat Cardiac Sarcoplasmic Reticulum Regulates Calcium-Induced Calcium Release
Authors: Gennady Cherednichenko, Aleksey V. Zima, Wei Feng, Saul Schaefer, Lothar A. Blatter, Isaac N. Pessah
Journal: Circulation Research (2003)

NADH and Ca 2+ have important regulatory functions in cardiomyocytes related to excitation-contraction coupling and ATP production. To elucidate elements of these functions, we examined the effect of NADH on sarcoplasmic reticulum (SR) Ca 2+ release and the mechanisms of this regulation. Physiological concentrations of cytosolic NADH inhibited ryanodine receptor type 2 (RyR2)–mediated Ca 2+ -induced Ca 2+ release (CICR) from SR membranes (IC 50 =120 μmol/L) and significantly lowered single channel open probability. In permeabilized single ventricular cardiomyocytes, NADH significantly inhibited the amplitude and frequency of spontaneous Ca 2+ release. Blockers of electron transport prevented the inhibitory effect of NADH on CICR in isolated membranes and permeabilized cells, as well as on the activity of RyR2 channels reconstituted in lipid bilayer. An endogenous NADH oxidase activity from rat heart copurified with SR enriched with RyR2. A significant contribution by mitochondria was excluded as NADH oxidation by SR exhibited &gt;9-fold higher catalytic activity (8.8 μmol/mg protein per minute) in the absence of exogenous mitochondrial complex I (ubiquinone) or complex III (cytochrome c ) electron acceptors, but was inhibited by rotenone and pyridaben (IC 50 =2 to 3 nmol/L), antimycin A (IC 50 =13 nmol/L), and diphenyleneiodonium (IC 50 =28 μmol/L). Cardiac junctional SR treated with [ 3 H](trifluoromethyl)diazirinyl-pyridaben specifically labeled a single 23-kDa PSST-like protein. These data indicate that NADH oxidation is tightly linked to, and essential for, negative regulation of the RyR2 complex and is a likely component of an important physiological negative-feedback mechanism coupling SR Ca 2+ fluxes and mitochondrial energy production.
α4-Integrin+ endothelium derived from primate embryonic stem cells generates primitive and definitive hematopoietic cells
Authors: Gen Shinoda, Katsutsugu Umeda, Toshio Heike, Masato Arai, Akira Niwa, Feng Ma, Hirofumi Suemori, Hong Yuan Luo, David H. K. Chui, Ryuzo Torii, Masabumi Shibuya, Norio Nakatsuji, Tatsutoshi Nakahata
Journal: Blood (2006)
Bronchoalveolar and systemic cytokine profiles in patients with ARDS, severe pneumonia and cardiogenic pulmonary oedema
Authors: H Schutte, J Lohmeyer, S Rosseau, S Ziegler, C Siebert, H Kielisch, H Pralle, F Grimminger, H Morr, W Seeger
Journal: European Respiratory Journal (1996)

The aim of this study was to investigate whether bronchoalveolar lavage (BAL) and serum levels of proinflammatory cytokines discriminate between different entities of patients with acute respiratory failure. BAL and circulating concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor-alpha (TNF-alpha) were measured in 74 mechanically-ventilated patients and 17 healthy controls. Patients were classified as cardiogenic pulmonary oedema (CPO), acute respiratory distress syndrome (ARDS), primary severe pneumonia (PN) and a combined group (PN+ARDS). In all patients with ARDS and/or PN, markedly elevated BAL levels of IL-6 and IL-8 were detected, which were significantly greater than levels in CPO and healthy controls. Absolute quantities and time-course of these cytokines did not differentiate between the absence and presence of lung infection, or different categories of PN. Similarly, circulating IL-6 levels were comparably elevated in patients with ARDS and/or PN, whereas circulating IL-8 concentrations were inconsistently increased. TNF-alpha was rarely detected in BAL samples, but increased serum concentrations were measured in ARDS and/or PN patients. Bronchoalveolar lavage levels of interleukin-6 and interleukin-8, but not tumour necrosis factor-alpha, and serum concentrations of interleukin-6 are consistently elevated in acute respiratory distress syndrome and/or severe pneumonia, discriminating these entities from cardiogenic pulmonary oedema. Alveolar and systemic cytokine profiles do not differentiate between acute respiratory distress syndrome in the absence of lung infection and states of severe primary or secondary pneumonia, which evidently present with comparable local and systemic inflammatory sequelae.
Validation and extension of an empirical Bayes method for SNP calling on Affymetrix microarrays
Authors: Shin Lin, Benilton Carvalho, David J Cutler, Dan E Arking, Aravinda Chakravarti, Rafael A Irizarry
Journal: Genome biology (2008)

Multiple algorithms have been developed for the purpose of calling single nucleotide polymorphisms (SNPs) from Affymetrix microarrays. We extend and validate the algorithm CRLMM, which incorporates HapMap information within an empirical Bayes framework. We find CRLMM to be more accurate than the Affymetrix default programs (BRLMM and Birdseed). Also, we tie our call confidence metric to percent accuracy. We intend that our validation datasets and methods, refered to as SNPaffycomp, serve as standard benchmarks for future SNP calling algorithms.
Effects of a Caloric Restriction Weight Loss Diet and Exercise on Inflammatory Biomarkers in Overweight/Obese Postmenopausal Women: A Randomized Controlled Trial
Authors: Ikuyo Imayama, Cornelia M. Ulrich, Catherine M. Alfano, Chiachi Wang, Liren Xiao, Mark H. Wener, Kristin L. Campbell, Catherine Duggan, Karen E. Foster-Schubert, Angela Kong, Caitlin E. Mason, Ching-Yun Wang, George L. Blackburn, Carolyn E. Bain, Henry J. Thompson, Anne McTiernan
Journal: Cancer Research (2012)

Abstract Obese and sedentary persons have increased risk for cancer; inflammation is a hypothesized mechanism. We examined the effects of a caloric restriction weight loss diet and exercise on inflammatory biomarkers in 439 women. Overweight and obese postmenopausal women were randomized to 1-year: caloric restriction diet (goal of 10% weight loss, N = 118), aerobic exercise (225 min/wk of moderate-to-vigorous activity, N = 117), combined diet + exercise (N = 117), or control (N = 87). Baseline and 1-year high-sensitivity C-reactive protein (hs-CRP), serum amyloid A (SAA), interleukin-6 (IL-6), leukocyte, and neutrophil levels were measured by investigators blind to group. Inflammatory biomarker changes were compared using generalized estimating equations. Models were adjusted for baseline body mass index (BMI), race/ethnicity, and age. Four hundred and thirty-eight (N = 1 in diet + exercise group was excluded) were analyzed. Relative to controls, hs-CRP decreased by geometric mean (95% confidence interval, P value): 0.92 mg/L (0.53–1.31, P &amp;lt; 0.001) in the diet and 0.87 mg/L (0.51–1.23, P &amp;lt; 0.0001) in the diet + exercise groups. IL-6 decreased by 0.34 pg/mL (0.13–0.55, P = 0.001) in the diet and 0.32 pg/mL (0.15–0.49, P &amp;lt; 0.001) in the diet + exercise groups. Neutrophil counts decreased by 0.31 × 109/L (0.09–0.54, P = 0.006) in the diet and 0.30 × 109/L (0.09–0.50, P = 0.005) in the diet + exercise groups. Diet and diet + exercise participants with 5% or more weight loss reduced inflammatory biomarkers (hs-CRP, SAA, and IL-6) compared with controls. The diet and diet + exercise groups reduced hs-CRP in all subgroups of baseline BMI, waist circumference, CRP level, and fasting glucose. Our findings indicate that a caloric restriction weight loss diet with or without exercise reduces biomarkers of inflammation in postmenopausal women, with potential clinical significance for cancer risk reduction. Cancer Res; 72(9); 2314–26. ©2012 AACR.
Marked elevation of the chemokine CCL18/PARC in Gaucher disease: a novel surrogate marker for assessing therapeutic intervention
Authors: Rolf G. Boot, Marri Verhoek, Maaike de Fost, Carla E. M. Hollak, Mario Maas, Boris Bleijlevens, Marielle J. van Breemen, Marjan van Meurs, Leonie A. Boven, Jon D. Laman, Mary Teresa Moran, Timothy M. Cox, Johannes M. F. G. Aerts
Journal: Blood (2003)
Induction of Ia antigen in rat epidermal cells and gut epithelium by immunological stimuli.
Authors: A N Barclay, D W Mason
Journal: The Journal of Experimental Medicine (1982)

The expression of Ia antigen in rat keratinocytes and gut epithelium was found to be inducible by a variety of immunological stimuli. Graft-vs.-host disease (GvHD) was accompanied by the appearance of Ia antigen in both sites, whereas local immunological stimuli, such as a contact-sensitizing agent applied to the skin and Trichinella spiralis infection of the gut, caused the expression of Ia antigen confined to the sites of contact of these stimuli with the tissues involved. Both T helper and T cytotoxic/suppressor subsets of parental lymphocytes, used to produce GvHD in F1 hybrid recipients, induce Ia expression in the skin and gut of these hosts, but simultaneous removal of both subsets from the donor inocula prevented induction. The Ia antigen expression associated with GvHD was shown to be of host origin but was not acquired from bone marrow-derived cells. Attempts to detect Ia antigen in serum or lymph of rats with GvHD gave negative results, and it was shown that Ia+ cells in the lamina propria of the small intestine did not take up detectable amounts of Ia antigen from the Ia+ intestinal epithelium. It appears that the local recognition of antigen by T lymphocytes can result in the induction of Ia antigen in keratinocytes and in the epithelial cells of the intestine. This antigen is synthesized by the cells in which it is found, and the observation that immunological stimuli are responsible for its appearance suggests that its role is an immunological one. Failure to find evidence that the gut epithelium Ia antigen was transferred to lymph or taken up by other Ia+ cells in the intestinal villi supports the view that this Ia (and, by analogy, that found in keratinocytes) serves a local function, and the possibility that it is involved in antigen presentation to T cells is discussed.
Structural Biology of Shared Cytokine Receptors
Authors: Xinquan Wang, Patrick Lupardus, Sherry L. LaPorte, K. Christopher Garcia
Journal: Annual Review of Immunology (2007)

Recent structural information for complexes of cytokine receptor ectodomains bound to their ligands has significantly expanded our understanding of the macromolecular topology and ligand recognition mechanisms used by our three principal shared cytokine signaling receptors-gp130, gamma(c), and beta(c). The gp130 family receptors intricately coordinate three structurally unique cytokine-binding sites on their four-helix bundle cytokine ligands to assemble multimeric signaling complexes. These organizing principles serve as topological blueprints for the entire gp130 family of cytokines. Novel structures of gamma(c) and beta(c) complexes show us new twists, such as the use of a nonstandard sushi-type alpha receptors for IL-2 and IL-15 in assembling quaternary gamma(c) signaling complexes and an antiparallel interlocked dimer in the GM-CSF signaling complex with beta(c). Unlike gp130, which appears to recognize vastly different cytokine surfaces in chemically unique fashions for each ligand, the gamma(c)-dependent cytokines appear to seek out some semblance of a knobs-in-holes shape recognition code in order to engage gamma(c) in related fashions. We discuss the structural similarities and differences between these three shared cytokine receptors, as well as the implications for transmembrane signaling.
Clinical judgment in rheumatoid arthritis. II. Judging 'current disease activity' in clinical practice.
Authors: J R Kirwan, D M Chaput de Saintonge, C R Joyce, H L Currey
Journal: Annals of the Rheumatic Diseases (1983)

Two rheumatologists made judgments about 9current disease activity9 in real patients and 9paper patients9 with rheumatoid arthritis. Analysis of each set of judgments provides a model of judgment policy which contains only 3 clinical variables but explains over 94% of the variance in judgments. The judgment policy models differ markedly from each other and from the clinicians9 own perceptions of their behaviour. Judgment policy modelling offers a means of improving co-ordination between clinical investigators within and between centres.