tbuckley/cabot-search huggingface dataset:
Deactivation of the Parahippocampal Gyrus Preceding Auditory Hallucinations in Schizophrenia
Authors: Kelly M.J. Diederen, Sebastiaan F.W. Neggers, Kirstin Daalman, Jan Dirk Blom, Rutger Goekoop, René S. Kahn, Iris E.C. Sommer
Journal: American Journal of Psychiatry (2010)

Activation in a network of language-related regions has been reported during auditory verbal hallucinations. It remains unclear, however, how this activation is triggered. Identifying brain regions that show significant signal changes preceding auditory hallucinations might reveal the origin of these hallucinations.Twenty-four patients with a psychotic disorder indicated the presence of auditory verbal hallucinations during 3-Tesla functional magnetic resonance imaging by squeezing a handheld balloon. A one-sample t test was performed to reveal groupwise activation during hallucinations. To enable analysis of brain activation 6 to 0 seconds preceding hallucinations, a tailored 'selective averaging' method, without any a priori assumptions concerning the hemodynamic response profile, was performed. To control for motor-related activation, 15 healthy comparison subjects squeezed a balloon at matched time intervals.Groupwise analysis during auditory verbal hallucinations revealed brain activation in bilateral (right more than left) language-related regions and bilateral motor regions. Prominent deactivation preceding these hallucinations was observed in the left parahippocampal gyrus. In addition, significant deactivation preceding hallucinations was found in the left superior temporal, right inferior frontal, and left middle frontal gyri as well as in the right insula and left cerebellum. No significant signal changes were revealed prior to the matched balloon squeezing among the comparison subjects.Auditory verbal hallucinations in patients with a psychotic disorder are consistently preceded by deactivation of the parahippocampal gyrus. The parahippocampus has been hypothesized to play a central role in memory recollection, sending information from the hippocampus to the association areas. Dysfunction of this region could trigger inadequate activation of right language areas during auditory hallucinations.
Obesity Impacts Access to Kidney Transplantation
Authors: Dorry L. Segev, Christopher E. Simpkins, Richard E. Thompson, Jayme E. Locke, Daniel S. Warren, Robert A. Montgomery
Journal: Journal of the American Society of Nephrology (2007)

Current billing practices and mandates to report surgical outcomes are disincentives to surgical treatment of obese patients, who are at increased risk for longer hospital stays and higher complication rates. The objective of this study was to quantify the independent association between body mass index (BMI) and waiting time for kidney transplantation to identify potential provider bias against surgical treatment of the obese. A secondary data analysis was performed of a prospective cohort of 132,353 patients who were registered for kidney transplantation in the United States between 1995 and 2006. Among all patients awaiting kidney transplantation, the likelihood of receiving a transplant decreased with increasing degree of obesity, categorized by ranges of BMI (adjusted hazard ratios 0.96 for overweight, 0.93 for obese, 0.72 for severely obese, and 0.56 for morbidly obese, compared with a reference group of patients with normal BMI). Similarly, the likelihood of being bypassed when an organ became available increased in a graded manner with category of obesity (adjusted incidence rate ratio 1.02 for overweight, 1.05 for obese, 1.11 for severely obese, and 1.22 for morbidly obese). Although matching an available organ with an appropriate recipient requires clinical judgment, which could not be fully captured in this study, the observed differences are dramatic and warrant further studies to understand this effect better and to design a system that is less susceptible to unintended bias.
THE QUANTITATIVELY MINOR ROLE OF CARBOHYDRATE IN OXIDATIVE METABOLISM BY SKELETAL MUSCLE IN INTACT MAN IN THE BASAL STATE. MEASUREMENTS OF OXYGEN AND GLUCOSE UPTAKE AND CARBON DIOXIDE AND LACTATE PRODUCTION IN THE FOREARM 12
Authors: Reubin Andres, Gordon Cader, Kenneth L. Zierler
Journal: Journal of Clinical Investigation (1956)

Skeletal muscle accounts for some 40 per cent of body weight. Presumably, by virtue of its bulk as the largest mass of tissue, its metabolism may be a major factor in total body economy and yet surprisingly little is known of the quantitative characteristics of metabolism of skeletal muscle. Studies of excised muscle and its extracts have provided a rich background relating to the metabolic capabilities of muscle. They have shown a great deal about the apparatus with which muscle is equipped to perform its functions in dissimilating metabolites but they fail to reveal the quantitative importance of particular pathways of dissimilation in the total scheme.
Opioid Receptor Types and Subtypes: The delta Receptor as a Model
Authors: P A Zaki, E J Bilsky, T W Vanderah, J Lai, C J Evans, F Porreca
Journal: The Annual Review of Pharmacology and Toxicology (1996)

Opioid Receptor Types and Subtypes: The delta Receptor as a Model, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/pharmtox/36/1/annurev.pa.36.040196.002115-1.gif
Phase III Study of Enzastaurin Compared With Lomustine in the Treatment of Recurrent Intracranial Glioblastoma
Authors: Wolfgang Wick, Vinay K. Puduvalli, Marc C. Chamberlain, Martin J. van den Bent, Antoine F. Carpentier, Lawrence M. Cher, Warren Mason, Michael Weller, Shengyan Hong, Luna Musib, Astra M. Liepa, Donald E. Thornton, Howard A. Fine
Journal: Journal of Clinical Oncology (2010)

This phase III open-label study compared the efficacy and safety of enzastaurin versus lomustine in patients with recurrent glioblastoma (WHO grade 4).Patients were randomly assigned 2:1 to receive 6-week cycles of enzastaurin 500 mg/d (1,125-mg loading dose, day 1) or lomustine (100 to 130 mg/m(2), day 1). Assuming a 45% improvement in progression-free survival (PFS), 397 patients were required to provide 80% power to achieve statistical significance at a one-sided level of .025.Enrollment was terminated at 266 patients (enzastaurin, n = 174; lomustine, n = 92) after a planned interim analysis for futility. Patient characteristics were balanced between arms. Median PFS (1.5 v 1.6 months; hazard ratio [HR] = 1.28; 95% CI, 0.97 to 1.70), overall survival (6.6 v 7.1 months; HR = 1.20; 95% CI, 0.88 to 1.65), and 6-month PFS rate (P = .13) did not differ significantly between enzastaurin and lomustine, respectively. Stable disease occurred in 38.5% and 35.9% of patients and objective response occurred in 2.9% and 4.3% of patients, respectively. Time to deterioration of physical and functional well-being and symptoms did not differ between arms (HR = 1.12; P = .54). Four patients discontinued enzastaurin because of drug-related serious adverse events (AEs). Eleven patients treated with enzastaurin died on study (four because of AEs; one was drug-related). All four deaths that occurred in patients receiving lomustine were disease-related. Grade 3 to 4 hematologic toxicities were significantly higher with lomustine (46 events) than with enzastaurin (one event; P < or = .001).Enzastaurin was well tolerated and had a better hematologic toxicity profile but did not have superior efficacy compared with lomustine in patients with recurrent glioblastoma.
Epicardial Outgrowth Inhibition Leads to Compensatory Mesothelial Outflow Tract Collar and Abnormal Cardiac Septation and Coronary Formation
Authors: Adriana C. Gittenberger-de Groot, Mark-Paul F.M. Vrancken Peeters, Maarten Bergwerff, Monica M.T. Mentink, Robert E. Poelmann
Journal: Circulation Research (2000)

In the present study, we investigated the modulatory role of the epicardium in myocardial and coronary development. Epicardial cell tracing experiments have shown that epicardium-derived cells are the source of interstitial myocardial fibroblasts, cushion mesenchyme, and smooth muscle cells. Epicardial outgrowth inhibition studies show abnormalities of the compact myocardial layer, myocardialization of cushion tissue, looping, septation, and coronary vascular formation. Lack of epicardial spreading is partly compensated by mesothelial outgrowth over the conotruncal region. Heterospecific epicardial transplant is able to partially rescue the myocardial development, as well as septation and coronary formation.
Twenty-fourth Annual Pezcoller Symposium: Molecular Basis for Resistance to Targeted Agents
Authors: Richard Marais, William Sellers, David Livingston, Enrico Mihich
Journal: Cancer Research (2012)

The mechanisms of genetically determined mechanisms of resistance to several target drugs were discussed in breast cancer, melanoma, colorectal and prostate cancers, chronic myelogenous leukemia, small cell lung cancer, and medulloblastoma. In each case, heterogeneity of mechanisms was emphasized. In melanoma, therapeutic interference with the effects of BRAF mutations was repeatedly discussed. It was also reported that anti-CTLA4 antibodies provided the first treatment improving survival of patients with stage IV melanoma. Epithelial-mesenchymal transition (EMT) was introduced as a mechanism of resistance, particularly in lung and pancreatic cancer, where the role of microenvironment factors was also indicated. In colorectal and prostate cancers, the use of liquid biopsies, namely, measurements of tumor nucleic acid in blood, were indicated as a way to obtain whole-tumor assessment instead of the partial assessment obtainable with traditional biopsies. Knowledge of the mechanisms of drug action and resistance was stressed to be essential for the design of new agents and combination of agents aimed at increasing antitumor effectiveness and overcoming resistance.
The Role of Selectins in Glomerular Leukocyte Recruitment in Rat Anti-Glomerular Basement Membrane Glomerulonephritis
Authors: AN S. DE VRIESE, KARLHANS ENDLICH, MARLIES ELGER, NORBERT H. LAMEIRE, ROBERT C. ATKINS, HUI Y. LAN, ALAIN RUPIN, WILHELM KRIZ, MICHAEL W. STEINHAUSEN
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Leukocytes play a central role in the pathogenesis of anti-glomerular basement membrane glomerulonephritis (anti-GBM GN). Understanding the mechanisms underlying their recruitment in the glomerulus is of critical importance, because this may lead to more specific anti-inflammatory drug design. The requirement for integrins, especially from the β 2 group, and their Ig superfamily counter-receptors has been established, however, the role of selectins remains controversial. An intravital microscopy technique was developed to study concomitantly the glomerular and venular leukocyte kinetics and the hemodynamic alterations in a rat model of anti-GBM GN, induced by injection of 10 mg of nephrotoxic serum (NTS). Histologic studies of the kidney were performed in parallel and urinary protein excretion was measured. The animals received NTS alone or were pretreated with either a monoclonal antibody against the β 2 integrin CD11b (OX42, 4 mg/kg) or fucoidan F7 (FF7, 8 mg/kg), an oligosaccharide that blocks both L- and P-selectin function. Administration of NTS resulted in a time-dependent increase in the number of adherent leukocytes in the glomeruli and a parallel decrease of the perfused glomerular capillary area. Substantial proteinuria was observed. Pretreatment with OX42 significantly attenuated these changes. FF7 almost abolished the rolling of the leukocytes in the venules, thus demonstrating efficient anti-selectin activity. Nevertheless, FF7 had no influence on the glomerular events or on the development of proteinuria. These results confirm that glomerular leukocyte adhesion in anti-GBM GN is CD11b-dependent. However, selectin-mediated interaction between the leukocytes and the glomerular capillary endothelium does not appear to be a prerequisite for leukocyte adhesion in the glomerulus. These results therefore question the potential utility of anti-selectin therapy in the treatment of anti-GBM GN.
Clinical predictors of fetal and maternal outcome in Chinese patients with systemic lupus erythematosus
Authors: M Y Mok
Journal: Annals of the Rheumatic Diseases (2004)

Maternal and fetal outcome of pregnancy in patients with systemic lupus erythematosus (SLE) depends very much on the composition of the patient cohort being analysed.

We performed a retrospective study to identify the clinical predictive factors for unfavourable pregnancy outcome in our Chinese patients with SLE from a homogeneous cohort being followed up at the university rheumatology clinic during the period 1982–96. Ninety one pregnancies from 66 patients were identified. Antiphospholipid antibodies (aPL), including lupus anticoagulant (LAC) and/or IgG anticardiolipin antibodies, were present in 18/66 (27%) patients. In 33/80 (41%) pregnancies resulting in live births, patients had a past history of lupus nephritis. Only one patient had impaired renal function, two had significant proteinuria ⩾1 g/day, and four had stable hypertension while receiving antihypertensive drugs …
Establishment of a hybridoma secreting a monoclonal antibody specific for activated tumoricidal macrophages.
Authors: T Taniyama, T Watanabe
Journal: The Journal of Experimental Medicine (1982)

New activated macrophage-specific antigen (AcM.1) detected by a monoclonal antibody has been described. The AcM.1 antigen was only detectable on activated macrophages induced by pyran and Corynebacterium parvum but not on resident or thioglycollate medium (TGC), proteose-peptone, and mineral oil-elicited macrophages, and not on blood monocytes and neutrophils. Activated macrophages induced by pyran and C. parvum, as expected, exhibited tumor cytotoxicity, whereas TGC-elicited macrophages did not show any cytotoxicity. Moreover, pretreatment of pyran-activated peritoneal exudate cells with AcM.1 antibody plus complement abolished approximately 80% cytotoxicity. Thus, this AcM.1 antigen detected by a monoclonal antibody is the first unique marker of activated tumoricidal macrophages and should provide a useful probe for investigating the mechanisms of activation or differentiation of macrophages.
Capecitabine plus oxaliplatin (XELOX) versus 5-fluorouracil/folinic acid plus oxaliplatin (FOLFOX-4) as second-line therapy in metastatic colorectal cancer: a randomized phase III noninferiority study
Authors: M.L. Rothenberg, J.V. Cox, C. Butts, M. Navarro, Y.-J. Bang, R. Goel, S. Gollins, L.L. Siu, S. Laguerre, D. Cunningham
Journal: Annals of Oncology (2008)
Multiple cytokines and chemokines are associated with rheumatoid arthritis-related autoimmunity in first-degree relatives without rheumatoid arthritis: Studies of the Aetiology of Rheumatoid Arthritis (SERA)
Authors: Jan M Hughes-Austin, Kevin D Deane, Lezlie A Derber, Jason R Kolfenbach, Gary O Zerbe, Jeremy Sokolove, Lauren J Lahey, Michael H Weisman, Jane H Buckner, Ted R Mikuls, James R O'Dell, Richard M Keating, Peter K Gregersen, William H Robinson, V Michael Holers, Jill M Norris
Journal: Annals of the Rheumatic Diseases (2012)

Objective We investigated whether rheumatoid arthritis (RA)-related autoantibodies were associated with systemic inflammation in a prospective cohort of first-degree relatives (FDRs) of RA probands, a population without RA but at increased risk for its future development. Methods We studied 44 autoantibody positive FDRs, of whom 29 were rheumatoid factor (RF) positive, 25 were positive for the high risk autoantibody profile (HRP), that is, positive for anti-cyclic citrullinated peptide and/or for at least two RF IgM, IgG or IgA isotypes, and nine FDRs who were positive for both; and 62 FDRs who were never autoantibody positive. Twenty-five cytokines/chemokines were measured using a bead-based assay in serum. As a comprehensive measure of inflammation, we calculated a Cytokine Score by summing all cytokine/chemokine levels, weighted by their regression coefficients for RA-autoantibody association. We compared C-reactive protein, individual cytokines/chemokines and Cytokine Score to the outcomes: positivity for RF and for the HRP using logistic regression. Results Adjusting for age, sex, ethnicity and ever smoking, the Cytokine Score and levels of IL-6 and IL-9 were associated with both RF and HRP. IL-2, granulocyte macrophage-colony stimulating factor (GM-CSF), and interferon (IFN)-γ were associated with HRP only. Associations between the Cytokine Score and RF and HRP positivity were replicated in an independent military personnel cohort. Conclusions In first-degree relatives of patients with RA, RA-related autoimmunity is associated with inflammation, as evidenced by associations with multiple cytokines and chemokines.
Role of the caspase-1 inflammasome in <i>Salmonella typhimurium</i> pathogenesis
Authors: Maria Lara-Tejero, Fayyaz S. Sutterwala, Yasunori Ogura, Ethan P. Grant, John Bertin, Anthony J. Coyle, Richard A. Flavell, Jorge E. Galán
Journal: The Journal of Experimental Medicine (2006)

Caspase-1 is activated by a variety of stimuli after the assembly of the “inflammasome,” an activating platform made up of a complex of the NOD-LRR family of proteins. Caspase-1 is required for the secretion of proinflammatory cytokines, such as interleukin (IL)-1β and IL-18, and is involved in the control of many bacterial infections. Paradoxically, however, its absence has been reported to confer resistance to oral infection by Salmonella typhimurium. We show here that absence of caspase-1 or components of the inflammasome does not result in resistance to oral infection by S. typhimurium, but rather, leads to increased susceptibility to infection.
Relationship between bioimpedance, thermodilution, and ventriculographic measurements in experimental congestive heart failure
Authors: F. G Spinale, D. A Hendrick, F. A Crawford, B. A Carabello
Journal: Cardiovascular Research (1990)

Journal Article Relationship between bioimpedance, thermodilution, and ventriculographic measurements in experimental congestive heart failure Get access Francis G Spinale, Francis G Spinale Search for other works by this author on: Oxford Academic PubMed Google Scholar David A Hendrick, David A Hendrick Search for other works by this author on: Oxford Academic PubMed Google Scholar Fred A Crawford, Fred A Crawford Search for other works by this author on: Oxford Academic PubMed Google Scholar Blase A Carabello Blase A Carabello Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 24, Issue 5, May 1990, Pages 423–429, https://doi.org/10.1093/cvr/24.5.423 Published: 01 May 1990 Article history Accepted: 16 January 1989 Received: 23 May 1989 Published: 01 May 1990
Gefitinib Induction of<i>In vivo</i>Detectable Signals by Bcl-2/Bcl-xL Modulation of Inositol Trisphosphate Receptor Type 3
Authors: Antonella Zannetti, Francesca Iommelli, Rosa Fonti, Angela Papaccioli, Jvana Sommella, Anna Lettieri, Giuseppe Pirozzi, Roberto Bianco, Giampaolo Tortora, Marco Salvatore, Silvana Del Vecchio
Journal: Clinical Cancer Research (2008)

Abstract Purpose: To test whether epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) induce detectable signals in tumor cells and whether such signals may reveal alterations of the apoptotic program. Experimental Design: Tumor cells were treated with gefitinib or erlotinib and tested for their ability to accumulate 99mTc-Sestamibi, a radiolabeled lipophilic cation that localizes in mitochondria. Then we tested whether Bcl-2 and Bcl-xL alter the pattern of drug-dependent tracer accumulation while reducing tumor cell sensitivity to EGFR TKIs. The mechanism underlying the pattern of tracer accumulation was elucidated. Finally, imaging studies were done in animal models and lung cancer patients before and after treatment with EGFR TKIs using single-photon emission computed tomography and 99mTc-Sestamibi. Results: Gefitinib increases accumulation of 99mTc-Sestamibi in Bcl-2–overexpressing cells and enhances the physical interaction of phosphorylated Bcl-2 with inositol trisphosphate receptor type 3 (IP3R3). Consequently, a relative increase of cytosolic and mitochondrial calcium levels occurs. Similarly, lung cancer cells showed an increase of tracer uptake and an enhanced interaction of Bcl-xL with IP3R3 on exposure to erlotinib concentrations achievable in plasma. The occurrence of these interactions was associated with an enhanced EGFR TKI–induced apoptosis resistance. Posttreatment imaging studies in nude mice bearing control and Bcl-2–overexpressing breast carcinomas showed a high tumor uptake of the tracer whereas baseline studies failed to visualize tumors. Similarly, an enhancement of tracer uptake could be detected in patients with lung cancer treated with erlotinib. Conclusion: EGFR TKIs generate detectable signals by Bcl-2/Bcl-xL modulation of IP3R3 in tumor cells.
A Defect in Tryptophan Catabolism Impairs Tolerance in Nonobese Diabetic Mice
Authors: Ursula Grohmann, Francesca Fallarino, Roberta Bianchi, Ciriana Orabona, Carmine Vacca, Maria C. Fioretti, Paolo Puccetti
Journal: The Journal of Experimental Medicine (2003)

The predisposition of nonobese diabetic (NOD) mice to develop autoimmunity reflects deficiencies in both peripheral and central tolerance. Several defects have been described in these mice, among which aberrant antigen-presenting cell function and peroxynitrite formation. Prediabetes and diabetes in NOD mice have been targeted with different outcomes by a variety of immunotherapies, including interferon (IFN)-γ. This cytokine may be instrumental in specific forms of tolerance by virtue of its ability to activate immunosuppressive tryptophan catabolism. Here, we provide evidence that IFN-γ fails to induce tolerizing properties in dendritic cells from highly susceptible female mice early in prediabetes. This effect is associated with impaired tryptophan catabolism, is related to transient blockade of the Stat1 pathway of intracellular signaling by IFN-γ, and is caused by peroxynitrite production. However, the use of a peroxynitrite inhibitor can rescue tryptophan catabolism and tolerance in those mice. This is the first report of an experimental autoimmune disease in which defective tolerance is causally linked to impaired tryptophan catabolism.
Inflammatory Bowel Disease Environmental Risk Factors: A Population-Based Case–Control Study of Middle Eastern Migration to Australia
Authors: Yanna Ko, Viraj Kariyawasam, Mohamad Karnib, Rhys Butcher, Douglas Samuel, Ahmad Alrubaie, Nabil Rahme, Charles McDonald, James Cowlishaw, Peter Katelaris, Gavin Barr, Brian Jones, Susan Connor, Gokulan Paven, Grace Chapman, Gordon Park, Richard Gearry, Rupert W. Leong
Journal: Clinical Gastroenterology and Hepatology (2015)
Neocortical size and language
Authors: R. I. M. Dunbar
Journal: Behavioral and Brain Sciences (1995)

Abstract In my target article, I argued (1) that the relationship between neocortical size and group size in primates implies that there is a cognitive limit on the size of human groups, and (2) that time constraints forced the evolution of language as a more efficient means of bonding the large groups that humans evolved. The doubts about these claims raised by these additional commentaries largely reflect misinterpretation of my original claims.