tbuckley/cabot-search huggingface dataset:
Selective Speech Perception Alterations in Schizophrenic Patients Reporting Hallucinated “Voices”
Authors: Ralph E. Hoffman, Jill Rapaport, Carolyn M. Mazure, Donald M. Quinlan
Journal: American Journal of Psychiatry (1999)

The authors tested a model of hallucinated "voices" based on a neural network computer simulation of disordered speech perception.Twenty-four patients with schizophrenia spectrum disorders who reported hallucinated voices were compared with 21 patients with schizophrenia spectrum disorders who did not report voices and 26 normal subjects. Narrative speech perception was assessed through use of a masked speech tracking task with three levels of superimposed phonetic noise. A sentence repetition task was used to assess grammar-dependent verbal working memory, and an auditory continuous performance task was used to assess nonlanguage attention.Masked speech tracking task and sentence repetition performance by hallucinating patients was impaired relative to both nonhallucinating patients and normal subjects. Although both hallucinating and nonhallucinating patients demonstrated auditory attention impairments when compared to normal subjects, the two patient groups did not differ with respect to these variables.Results support the hypothesis that hallucinated voices in schizophrenia arise from disrupted speech perception and verbal working memory systems rather than from nonlanguage cognitive or attentional deficits.
Plasma cell immunoglobulin secretion. Arrest is accompanied by alterations the golgi complex
Authors: AM Tartakoff, P Vassali, M Detraz
Journal: The Journal of Experimental Medicine (1977)

Conditions influencing Ig secretion by plasma cells have been studied with suspensions of murine plasma cells and myeloma cells by determining the release of (3)H-Ig after a pulse of biosynthetic labeling with L- [4,5-(3)H]-leucine. Ig secretion is insensitive to a variety of hormones, mediators, cyclic nucleotide derivatives, extracellular calcium depletion, and agents acting on mierotubules or microfilaments; i.e., to a number of factors which are involved in the regulation of secretion by cells with a storage compartment. On the other hand, Ig secretion is markedly inhibited by conditions which (a) lower intracellular calcium levels (ionophore A 23187 in Ca(++)-free medium), (b) induce partial sodium/potassium equilibration (the ionophores monensin and nigericin and, in the case of myeloma cells, ouabain and incubation in K(+)-free medium) or (c) uncouple oxidative phosphorylation. The first two situations are accompanied by striking alterations of the ultrastructural appearance of the Golgi complex, different in each case. These ultrastructural observations, together with autoradiographic experiments after a short pulse with L-[4,5-(3)H]-leucine, have led to the following hypothesis: (a) under Ca(++) depletion (3)H-Ig passes to Golgi vesicles but these vesicles are incapable of fusion or migration and therefore accumulate in exaggerated numbers in the Golgi area; (b) under partial Na(+)/K(+) equilibration, (3)H-Ig passes to Golgi vesicles which have an exaggerated tendency to fuse with other Golgi elements, thereby generating large vacuoles which store increasing amounts of Ig; (c) under energy block, multiple membrane fission and fusion events are inhibited and there is therefore, little intracellular transport of (3)H-Ig or alteration of cell ultrastructure.
Cardioverter defibrillator implantation without induction of ventricular fibrillation: a single-blind, non-inferiority, randomised controlled trial (SIMPLE)
Authors: Jeff S Healey, Stefan H Hohnloser, Michael Glikson, Jorg Neuzner, Phillipe Mabo, Xavier Vinolas, Josef Kautzner, Gilles O'Hara, Lieselot VanErven, Fredrik Gadler, Janice Pogue, Ursula Appl, Jim Gilkerson, Thierry Pochet, Kenneth M Stein, Bela Merkely, Susan Chrolavicius, Brandi Meeks, Csaba Foldesi, Bernard Thibault, Stuart J Connolly
Journal: The Lancet (2015)
Dysfunction of Early-Stage Visual Processing in Schizophrenia
Authors: Pamela D. Butler, Isaac Schechter, Vance Zemon, Stephen G. Schwartz, Vivienne C. Greenstein, James Gordon, Charles E. Schroeder, Daniel C. Javitt
Journal: American Journal of Psychiatry (2001)

Schizophrenia is associated with deficits in higher-order processing of visual information. This study evaluated the integrity of early visual processing in order to evaluate the overall pattern of visual dysfunction in schizophrenia.Steady-state visual-evoked potential responses were recorded over the occipital cortex in patients with schizophrenia and in age- and sex-matched comparison volunteers. Visual-evoked potentials were obtained for stimuli composed of isolated squares that were modulated sinusoidally in luminance contrast, number of squares, or chromatic contrast in order to emphasize magnocellular or parvocellular visual pathway activity.Responses of patients to magnocellular-biased stimuli were significantly lower than those of comparison volunteers. These lower response levels were observed in conditions using both low luminance contrast and large squares that biased processing toward the magnocellular pathway. In contrast, responses to stimuli that biased processing toward the parvocellular pathway were not significantly different between schizophrenia patients and comparison volunteers. A significant interaction of group and stimulus type was observed in the condition using low luminance contrast.These findings suggest a dysfunction of lower-level visual pathways, which was more prominent for magnocellular than parvocellular biased stimuli. The magnocellular pathway helps in orienting toward salient stimuli. A magnocellular pathway deficit could contribute to higher-level visual cognitive deficits in schizophrenia.
Evolution of environmental epidemiologic risk assessment.
Authors: H A Anderson
Journal: Environmental Health Perspectives (1985)

Epidemiology has historically played an important role in the recognition of causes for diseases affecting the health of the public. Initially, epidemiology was concerned with infectious diseases. Later it became involved in metabolic and dietary deficiency diseases. Most recently, epidemiology has addressed the question of the public health effects of chemicals from production facilities, accidental spills, and chemical waste disposal sites. Concurrent improvements in the sensitivity of chemical analyses have enabled the identification of chemicals arising from waste disposal sites in the soil, air, drinking water, and food supplies of neighboring residential areas, albeit usually at very low concentrations. This knowledge has created great concerns among the affected populations and their public health agencies. The responsibility for interpreting the potential severity of the health effects of these environmental contaminants has fallen to those scientists experienced in epidemiology. This has led to a subdiscipline, reactive epidemiology, which describes investigations focused on specific events, usually under emotion-laden circumstances, rather than scientific merit. The reactive epidemiologist is rigidly constrained as to the size, timing, and location of the study. There is a strong requirement for public communication skills. New data bases are needed including "sentinel" diseases that are linked to exposure to chemicals, records of land use, and residency data for the population at risk.
Two Components of Delayed Rectifier Current in Canine Atrium and Ventricle
Authors: Gary A. Gintant
Journal: Circulation Research (1996)

Abstract Because the number and characteristics of delayed rectifier K + current (I K ) components vary between species, the role of each component in the action potential and modulation by class III agents is uncertain. To address these issues, I K was assessed in adult isolated canine ventricular and atrial myocytes by using whole-cell and perforated-patch techniques. I K components were characterized by using two complementary approaches: a kinetic approach (based on biexponential fits to deactivating tail currents) and a pharmacological approach (using the methanesulfonanilide compound E-4031). In ventricular myocytes, two exponential tail current components were distinguished; these components differed in the voltage and time dependence of activation and the effect of lower [K + ] o . Both kinetic components contributed equally to peak tail current amplitude (measured at −35 mV) after a single 300-ms pulse to 5 mV, simulating an action potential. By use of E-4031, rapidly and slowly activating components of I K (I Kr and I Ks , respectively) that were analogous to tail components described kinetically were identified. The activation kinetics and rectification properties of canine I Kr and I Ks are qualitatively similar to those described previously for guinea pigs. In contrast, canine I Kr and I Ks deactivation kinetics differed markedly from those found in guinea pigs, with canine I Kr deactivating slowly (time constant τ, 2 to 3 s near −35 mV) and I Ks deactivating rapidly (τ, 150 ms near −35 mV and decreasing to 30 ms near −85 mV). E-4031 elicited reverse rate-dependent effects (greater drug-induced prolongation of the action potential at slower stimulation rates); this effect is inconsistent with the hypothesis attributing reverse rate dependence to incomplete I Ks deactivation during rapid stimulation (due to rapid deactivation of canine I Ks ). Two I K components with characteristics comparable to those found in ventricular myocytes were also observed in atrial myocytes. In conclusion, (1) I Kr - and I Ks -like components of I K are present in canine atrial and ventricular myocytes, with deactivation kinetics strikingly different from those found in guinea pigs, and (2) the rapid deactivation kinetics of canine I Ks do not support its role in reverse rate dependence with class III agents in this species.
Economics notes: Definitions of efficiency
Authors: S. Palmer, D. J Torgerson
Journal: BMJ (1999)

This is the third in a series of occasional notes on economics

Decision makers are increasingly faced with the challenge of reconciling growing demand for health care services with available funds.1 Economists argue that the achievement of (greater) efficiency from scarce resources should be a major criterion for priority setting. This note examines three concepts of efficiency: technical, productive, and allocative.

Efficiency measures whether healthcare resources are being used to get the best value for money.1 Health care can be seen an intermediate product, in the sense of being a means to the end of improved health. Efficiency is concerned with the relation between resource inputs (costs, in the form of labour, capital, or equipment) and either intermediate outputs (numbers treated, waiting time, etc) or final health outcomes (lives saved, life years gained, quality adjusted life years (QALYs)). Although many evaluations use intermediate outputs as a measure of effectiveness, this can …
Antiangiogenic Therapy of Cerebral Melanoma Metastases Results in Sustained Tumor Progression via Vessel Co-Option
Authors: William P. J. Leenders, Benno Küsters, Kiek Verrijp, Cathy Maass, Pieter Wesseling, Arend Heerschap, Dirk Ruiter, Andy Ryan, Robert de Waal
Journal: Clinical Cancer Research (2004)

Abstract Purpose: In the brain, tumors may grow without inducing angiogenesis, via co-option of the dense pre-existent capillary bed. The purpose of this study was to investigate how this phenomenon influences the outcome of antiangiogenic therapy. Experimental Design: Mice carrying brain metastases of the human, highly angiogenic melanoma cell line Mel57-VEGF-A were either or not treated with different dosages of ZD6474, a vascular endothelial growth factor (VEGF) receptor 2 tyrosine kinase inhibitor with additional activity against epidermal growth factor receptor. Effect of treatment was evaluated using contrast-enhanced magnetic resonance imaging (CE- MRI) and (immuno)morphologic analysis. Results: Placebo-treated Mel57-VEGF-A brain metastases evoked an angiogenic response and were highlighted in CE-MRI. After treatment with ZD6474 (100 mg/kg), CE-MRI failed to detect tumors in either prevention or therapeutic treatment regimens. However, (immuno)histologic analysis revealed the presence of numerous, small, nonangiogenic lesions. Treatment with 25 mg/kg ZD6474 also resulted in efficient blockade of vessel formation, but it did not fully inhibit vascular leakage, thereby still allowing visualization in CE-MRI scans. Conclusions: Our data show that, although angiogenesis can be effectively blocked by ZD6474, in vessel-dense organs this may result in sustained tumor progression via co-option, rather than in tumor dormancy. Importantly, blocking VEGF-A may result in undetectability of tumors in CE-MRI scans, leading to erroneous conclusions about therapeutic efficacy during magnetic resonance imaging follow-up. The maintenance of VEGF-A-induced vessel leakage in the absence of neovascularization at lower ZD6474 doses may be exploited to improve delivery of chemotherapeutic agents in combined treatment regimens of antiangiogenic and chemotherapeutic compounds.
Pro12Ala Polymorphism of the PPARγ2 Locus Modulates the Relationship Between Energy Intake and Body Weight in Type 2 Diabetic Patients
Authors: Olga Vaccaro, Emanuela Lapice, Antonella Monticelli, Manuela Giacchetti, Imma Castaldo, Rocco Galasso, Michele Pinelli, Giovanna Donnarumma, Angela A. Rivellese, Sergio Cocozza, Gabriele Riccardi
Journal: Diabetes Care (2007)

OBJECTIVE—We explore the relationship among BMI, habitual diet, and the Pro12Ala polymorphism in the peroxisome proliferator–activated receptor (PPAR)γ2. RESEARCH DESIGN AND METHODS—The Pro12Ala variant was characterized in 343 unrelated type 2 diabetic patients who were consecutively seen at the outpatient clinic of a health district of the province of Naples. Anthropometric and laboratory parameters were measured; habitual diet was assessed by a validated semiquantitative food frequency questionnaire. RESULTS—The overall frequency of Ala12 was 12% (n = 42). BMI was significantly higher in Ala carriers than non-Ala carriers, whereas total daily energy intake or macronutrient composition of the diet were similar in the two groups. For further analysis, participants were stratified according to genotype and sex-specific quartiles of energy intake. BMI increased in both genotype groups with increasing energy intake (P &amp;lt; 0.03). BMI was similar in Ala carriers and non-Ala carriers (30.0 vs. 30.1 kg/m2, P &amp;gt; 0.10) in the lower quartile of energy intake but significantly higher in Ala carriers in the upper quartile (36.0 vs. 32.1 kg/m2, P &amp;lt; 0.001). Average daily energy intake and diet composition were comparable within each quartile for carriers or noncarriers of the Ala allele. Relative to the noncarriers, Ala carriers had a significantly lower energy intake per kilogram body weight, thus suggesting that the Ala allele is associated with a higher food efficiency. The confounding role of medications, glucose control, and physical exercise was ruled out. CONCLUSIONS—This study provides evidence of a differential susceptibility to fat accumulation, and, hence, weight gain, in response to habitual high energy intake for Ala carriers compared with Pro/Pro homozygotes.
Effects of fat and carbohydrate meals on colonic motor response
Authors: Satish Sanku Chander Rao, R. Kavelock, J. Beaty, K. Ackerson, P. Stumbo
Journal: Gut (2000)

<h3>BACKGROUND</h3> Ingestion of a meal stimulates colonic motility. It is unclear whether the nutrient composition of a meal affects colonic motor response. <h3>AIMS</h3> To investigate and compare the effects of a predominantly fat or carbohydrate meal on colonic motility. <h3>METHODS</h3> In 18 healthy subjects, ambulatory colonic manometry was performed by placing a six sensor, solid state probe from the mid-transverse colon to the rectum. In a randomised, crossover design, 10 and 27 hours after probe placement, subjects received 4.18 MJ meals containing 60% calories from fat or carbohydrate sources. Preprandial and postprandial pressure activity and motor patterns were evaluated. <h3>RESULTS</h3> Both meals induced phasic activity with a greater area under the curve (p&lt;0.03) in the first postprandial hour, compared with the control period. Fat induced motor activity persisted longer (p&lt;0.05) than that of the carbohydrate meal, but the onset of motor response was slower (p&lt;0.001). Although both meals induced more (p&lt;0.001) propagating pressure waves, only the fat meal induced more (p&lt;0.05) simultaneous and retrograde waves. After both meals, 50% of subjects exhibited high amplitude (more than 103 mm Hg), prolonged duration (more than 13 seconds) propagating waves. Both meals induced greater activity (p&lt;0.05) in the transverse/descending colon than in the rectosigmoid colon. <h3>CONCLUSIONS</h3> Carbohydrate meals induce colonic motor response, but the effects are short lived when compared with fat meals. The prolonged, segmental, and retrograde phasic activity induced by the fat meal may delay colon transit. Thus meal composition influences colonic motor response.
Abnormal miR-148b Expression Promotes Aberrant Glycosylation of IgA1 in IgA Nephropathy
Authors: Grazia Serino, Fabio Sallustio, Sharon N. Cox, Francesco Pesce, Francesco P. Schena
Journal: Journal of the American Society of Nephrology (2012)

Aberrant O-glycosylation in the hinge region of IgA1 characterizes IgA nephropathy. The mechanisms underlying this abnormal glycosylation are not well understood, but reduced expression of the enzyme core 1, β1,3-galactosyltransferase 1 (C1GALT1) may contribute. In this study, high-throughput microRNA (miRNA) profiling identified 37 miRNAs differentially expressed in PBMCs of patients with IgA nephropathy compared with healthy persons. Among them, we observed upregulation of miR-148b, which potentially targets C1GALT1. Patients with IgA nephropathy exhibited lower C1GALT1 expression, which negatively correlated with miR-148b expression. Transfection of PBMCs from healthy persons with a miR-148b mimic reduced endogenous C1GALT1 mRNA levels threefold. Conversely, loss of miR-148b function in PBMCs of patients with IgA nephropathy increased C1GALT1 mRNA and protein levels to those observed in healthy persons. Moreover, we found that upregulation of miR-148b directly correlated with levels of galactose-deficient IgA1. In vitro, we used an IgA1-producing cell line to confirm that miR-148b modulates IgA1 O-glycosylation and the levels of secreted galactose-deficient IgA1. Taken together, these data suggest a role for miRNAs in the pathogenesis of IgA nephropathy. Abnormal expression of miR-148b may explain the aberrant glycosylation of IgA1, providing a potential pharmacologic target for IgA nephropathy.
Overall Survival and Updated Results for Sunitinib Compared With Interferon Alfa in Patients With Metastatic Renal Cell Carcinoma
Authors: Robert J. Motzer, Thomas E. Hutson, Piotr Tomczak, M. Dror Michaelson, Ronald M. Bukowski, Stéphane Oudard, Sylvie Negrier, Cezary Szczylik, Roberto Pili, Georg A. Bjarnason, Xavier Garcia-del-Muro, Jeffrey A. Sosman, Ewa Solska, George Wilding, John A. Thompson, Sindy T. Kim, Isan Chen, Xin Huang, Robert A. Figlin
Journal: Journal of Clinical Oncology (2009)

A randomized, phase III trial demonstrated superiority of sunitinib over interferon alfa (IFN-alpha) in progression-free survival (primary end point) as first-line treatment for metastatic renal cell carcinoma (RCC). Final survival analyses and updated results are reported.
Essential role of Gas6 for glomerular injury in nephrotoxic nephritis
Authors: Motoko Yanagita, Yoshikazu Ishimoto, Hidenori Arai, Kojiro Nagai, Tsuyoshi Ito, Toru Nakano, David J. Salant, Atsushi Fukatsu, Toshio Doi, Toru Kita
Journal: Journal of Clinical Investigation (2002)

Growth-arrest specific gene 6 (Gas6) is a vitamin K–dependent growth factor for mesangial and epithelial cells. To investigate whether Gas6 is essential for progressive glomerular injury, we constructed Gas6–/– mice and examined the role of Gas6 in accelerated nephrotoxic nephritis (NTN), a model of progressive glomerulonephritis. We found less mortality and proteinuria in Gas6–/– mice than in wild-type mice following injection of nephrotoxic serum. Glomerular cell proliferation, glomerular sclerosis, crescent formation, and deposition of fibrin/fibrinogen in glomeruli were also reduced in Gas6–/– mice. Furthermore, administering Gas6–/– mice recombinant wild-type Gas6, but not Gas6 lacking a previously characterized N-terminal γ-carboxyl group, induced massive proteinuria, glomerular cell proliferation, and glomerulosclerosis, comparable to responses seen in wild-type mice. These data indicate that Gas6 induces glomerular cell proliferation in NTN and suggest that this factor contributes to glomerular injury and the progression of chronic nephritis.
Efficacy of low and high dose inhaled corticosteroid in smokers versus non-smokers with mild asthma
Authors: J E M Tomlinson
Journal: Thorax (2005)

<b>Background:</b> Cigarette smokers with asthma are insensitive to short term inhaled corticosteroid therapy, but efficacy when given for a longer duration at different doses is unknown. <b>Methods:</b> Ninety five individuals with mild asthma were recruited to a multicentre, randomised, double blind, parallel group study comparing inhaled beclomethasone in doses of 400 μg or 2000 μg daily for 12 weeks in smokers and non-smokers. The primary end point was the change in morning peak expiratory flow (PEF). Secondary end points included evening PEF, use of reliever inhaler, number of asthma exacerbations, spirometric parameters, and asthma control score. <b>Results:</b> After 12 weeks of inhaled beclomethasone there was a considerable difference between the morning PEF measurements of smokers and non-smokers with asthma (−18 (95% CI −35 to −1), adjusted p = 0.035). Among those receiving 400 μg daily there was a difference between the mean (95% CI) morning PEF (l/min) in smokers and non-smokers (−25 (95% CI −45 to −4), adjusted p = 0.019) and in the number of asthma exacerbations (6 <i>v</i> 1 in smokers and non-smokers, respectively, p = 0.007). These differences were reduced between smokers and non-smokers receiving 2000 μg inhaled beclomethasone daily. <b>Conclusions:</b> Compared with non-smokers, smokers with mild persistent asthma are insensitive to the therapeutic effect of low dose inhaled corticosteroid treatment administered for a 12 week period. The disparity of the response between smokers and non-smokers appears to be reduced with high dose inhaled corticosteroid. These findings have important implications for the management of individuals with mild asthma who smoke.