tbuckley/cabot-search huggingface dataset:
Comparative Study of Trauma-Related Phenomena in Subjects With Pseudoseizures and Subjects With Epilepsy
Authors: William Fleisher, Douglas Staley, Patricia Krawetz, Neelon Pillay, John L Arnett, John Maher
Journal: American Journal of Psychiatry (2002)

The purpose of this study was to examine potential differences in measures of trauma-related phenomena between subjects with pseudoseizures and subjects with intractable epilepsy.Thirty-one adult subjects with pseudoseizures and 32 subjects with intractable epilepsy (confirmed by video-EEG) were recruited from the epilepsy unit of a tertiary care hospital. Each participant completed the Impact of Event Scale, the Davidson Trauma Scale, the Mississippi Scale for Combat-Related Posttraumatic Stress Disorder (PTSD), the Dissociative Experience Scale, and the Pittsburgh Sleep Quality Index, as well as demographic, seizure history, and family functioning measures.Subjects with pseudoseizures had significantly higher mean scores on the Davidson Trauma Scale, Mississippi Scale for Combat-Related PTSD, Impact of Event Scale, and Pittsburgh Sleep Quality Index than subjects with epilepsy. In addition, a significantly higher percentage of subjects with pseudoseizures had scores above the clinical cutoff level of 30 on the Dissociative Experience Scale.Subjects with pseudoseizures exhibited trauma-related profiles that differed significantly from those of epileptic comparison subjects and closely resembled those of individuals with a history of traumatic experiences. Interventions aimed at trauma-related issues may be beneficial for patients with pseudoseizures.
Embryonic Stem Cell–Derived Exosomes Promote Endogenous Repair Mechanisms and Enhance Cardiac Function Following Myocardial Infarction
Authors: Mohsin Khan, Emily Nickoloff, Tatiana Abramova, Jennifer Johnson, Suresh Kumar Verma, Prasanna Krishnamurthy, Alexander Roy Mackie, Erin Vaughan, Venkata Naga Srikanth Garikipati, Cynthia Benedict, Veronica Ramirez, Erin Lambers, Aiko Ito, Erhe Gao, Sol Misener, Timothy Luongo, John Elrod, Gangjian Qin, Steven R. Houser, Walter J. Koch, Raj Kishore
Journal: Circulation Research (2015)

Rationale: Embryonic stem cells (ESCs) hold great promise for cardiac regeneration but are susceptible to various concerns. Recently, salutary effects of stem cells have been connected to exosome secretion. ESCs have the ability to produce exosomes, however, their effect in the context of the heart is unknown. Objective: Determine the effect of ESC-derived exosome for the repair of ischemic myocardium and whether c-kit + cardiac progenitor cells (CPCs) function can be enhanced with ESC exosomes. Methods and Results: This study demonstrates that mouse ESC-derived exosomes (mES Ex) possess ability to augment function in infarcted hearts. mES Ex enhanced neovascularization, cardiomyocyte survival, and reduced fibrosis post infarction consistent with resurgence of cardiac proliferative response. Importantly, mES Ex augmented CPC survival, proliferation, and cardiac commitment concurrent with increased c-kit + CPCs in vivo 8 weeks after in vivo transfer along with formation of bonafide new cardiomyocytes in the ischemic heart. miRNA array revealed significant enrichment of miR290-295 cluster and particularly miR-294 in ESC exosomes. The underlying basis for the beneficial effect of mES Ex was tied to delivery of ESC specific miR-294 to CPCs promoting increased survival, cell cycle progression, and proliferation. Conclusions: mES Ex provide a novel cell–free system that uses the immense regenerative power of ES cells while avoiding the risks associated with direct ES or ES-derived cell transplantation and risk of teratomas. ESC exosomes possess cardiac regeneration ability and modulate both cardiomyocyte and CPC-based repair programs in the heart.
Distribution of inhaled 99mtechnetium labelled ultrafine carbon particle aerosol (Technegas) in human lungs
Authors: TC Amis, AB Crawford, A Davison, LA Engel
Journal: European Respiratory Journal (1990)

Using a gamma camera, we quantified the topographical intrapulmonary distribution of inhaled 100 ml boluses of Technegas (TG), an ultrafine dispersion of carbon aggregates labelled with 99mTc, and 133Xenon (Xe) in six seated, normal subjects, inhaling from residual volume (RV) and from within a 1 l volume range above functional residual capacity (FRC) at a flow less than 0.5 l.s-1. Following inspiration of air to total lung capacity (TLC) counts were recorded during a 20 s breathhold. Twenty min after administration of the final TG bolus (TGF) counts were again recorded (TG20). Upper (U), middle (M) and lower (L) zones, as well as central (C) and peripheral (P) regions were identified in each lung. The relative fractional concentration (Fr) of TG and Xe was calculated for all zones after RV and FRC boluses, using counts obtained during Xe equilibration. The U/M or U/L ratios for XeFr did not differ significantly from those for TGFr (paired t-test; p greater than 0.1). The P/C count ratio constitutes a penetration index, which for TG was 1.07 +/- 0.13 (mean +/- SD) that of Xe. After correction for radioactive decay, TG20 counts were no different from TGF counts. The results suggest that the intrapulmonary distribution and penetration of TG in normal lungs is no different from Xe and that stable deposition in the lung periphery makes TG suitable for multiple-view imaging of ventilation distribution.
Monogenic atrial fibrillation as pathophysiological paradigms
Authors: S. Mahida, S. A. Lubitz, M. Rienstra, D. J. Milan, P. T. Ellinor
Journal: Cardiovascular Research (2010)

Atrial fibrillation (AF) is the most common cardiac rhythm abnormality and represents a major burden, both to patients and to health-care systems. In recent years, increasing evidence from population-based studies has demonstrated that AF is a heritable condition. Although familial forms of AF have been recognized for many years, they represent a rare subtype of the arrhythmia. However, despite their limited prevalence, the identification of mutations in monogenic AF kindreds has provided valuable insights into the molecular pathways underlying the arrhythmia and a framework for investigating AF encountered in the general population. In contrast to these rare families, the typical forms of AF occurring in the community are likely to be multigenic and have significant environmental influences. Recently, genome-wide association studies have uncovered common sequence variants that confer increased susceptibility to the arrhythmia. In the future, the elucidation of the genetic substrate underlying both familial and more typical forms of AF will hopefully lead to the development of novel diagnostic tools as well as more targeted rhythm control strategies. In this article, we will focus on monogenic forms of AF and also provide an overview of case–control association studies for AF.
When can a second conservative approach be considered for ipsilateral breast tumour recurrence?
Authors: O. Gentilini, E. Botteri, N. Rotmensz, B. Santillo, N. Peradze, R.C. Saihum, M. Intra, A. Luini, V. Galimberti, A. Goldhirsch, U. Veronesi
Journal: Annals of Oncology (2006)
1330 IL28B GENOTYPE MAJOR AND RELAPSE OF PREVIOUS PEG-IFN/RBV THERAPY ARE THE CONVINCING PREDICTOR OF SUSTAINED VIROLOGICAL RESPONSE IN TELAPREVIR WITH PEG-IFN/RBV THERAPY
Authors: Y. Karino, I. Ozeki, J. Toyota, M. Imamura, M. Tsuge, K. Chayama, H. Sezaki, N. Akuta, H. Kumada
Journal: Journal of Hepatology (2011)
Intensive Multimodality Treatment for Children With Newly Diagnosed CNS Atypical Teratoid Rhabdoid Tumor
Authors: Susan N. Chi, Mary Ann Zimmerman, Xiaopan Yao, Kenneth J. Cohen, Peter Burger, Jaclyn A. Biegel, Lucy B. Rorke-Adams, Michael J. Fisher, Anna Janss, Claire Mazewski, Stewart Goldman, Peter E. Manley, Daniel C. Bowers, Anne Bendel, Joshua Rubin, Christopher D. Turner, Karen J. Marcus, Liliana Goumnerova, Nicole J. Ullrich, Mark W. Kieran
Journal: Journal of Clinical Oncology (2008)

Atypical teratoid rhabdoid tumor (ATRT) of the CNS is a highly malignant neoplasm primarily affecting young children, with a historic median survival ranging from 6 to 11 months. Based on a previous pilot series, a prospective multi-institutional trial was conducted for patients with newly diagnosed CNS ATRT.Treatment was divided into five phases: preirradiation, chemoradiation, consolidation, maintenance, and continuation therapy. Intrathecal chemotherapy was administered, alternating intralumbar and intraventricular routes. Radiation therapy (RT) was prescribed, either focal (54 Gy) or craniospinal (36 Gy, plus primary boost), depending on age and extent of disease at diagnosis.Between 2004 and 2006, 25 patients were enrolled; 20 were eligible for evaluation. Median age at diagnosis was 26 months (range, 2.4 months to 19.5 years). Gross total resection of the primary tumor was achieved in 11 patients. Fourteen patients had M0 disease at diagnosis, one patient had M2 disease, and five patients had M3 disease. Fifteen patients received radiation therapy: 11 focal and four craniospinal. Significant toxicities, in addition to the expected, included radiation recall (n = 2) and transverse myelitis (n = 1). There was one toxic death. Of the 12 patients who were assessable for chemotherapeutic response (pre-RT), the objective response rate was 58%. The objective response rate observed after RT was 38%. The 2-year progression-free and overall survival rates are 53% +/- 13% and 70% +/- 10%, respectively. Median overall survival has not yet been reached.This intensive multimodality regimen has resulted in a significant improvement in time to progression and overall survival for patients with this previously poor-prognosis tumor.
Chronic exposure of betaTC-6 cells to supraphysiologic concentrations of glucose decreases binding of the RIPE3b1 insulin gene transcription activator.
Authors: V Poitout, L K Olson, R P Robertson
Journal: Journal of Clinical Investigation (1996)

We have shown previously that chronic exposure of HIT-T15 cells to supraphysiologic glucose concentrations causes decreased insulin gene transcription and decreased binding activities of two beta-cell specific transcription factors, STF-1 and the RIPE3b1 activator, and have suggested that these events may provide a mechanism for glucose toxicity on beta-cell function. However, this contention can be criticized because it is not clear whether these observations are unique to the HIT-T15 cell or generalizable to other beta-cell lines and the islet. Therefore, we cultured betaTC-6 cells for up to 41 wk in either 11.1 or 0.8 mM glucose. We observed a passage-dependent decrease in insulin content and insulin mRNA levels in betaTC-6 cells chronically cultured in 11.1 mM glucose. Cells chronically cultured in 0.8 mM glucose had higher insulin mRNA levels than cells chronically cultured in 11.1 mM glucose. The relative activity of a chloramphenicol acetyl transferase (CAT) reporter gene controlled by the 5' regulatory region of the human insulin gene was decreased in late passage betaTC-6 cells chronically cultured in 11.1 mM glucose, but was preserved in late passages of cells chronically cultured in 0.8 mM glucose. Electromobility shift assays demonstrated that binding of a specific nuclear protein that recognizes the RIPE3b1 binding site of the insulin gene was markedly diminished in late passage cells chronically exposed to 11.1 mM glucose, whereas binding activities of STF-1 and ICE activators were unchanged. RIPE3b1 binding activity was preserved in late passage cells chronically exposed to 0.8 mM glucose. Mutation of the RIPE3b1 binding site almost completely abolished insulin gene transcription as well as binding activity. We conclude that chronic exposure of betaTC-6 cells to high glucose concentrations paradoxically decreases insulin gene transcription, in part, by decreasing activity of the trans-activating factor which binds to the RIPE3b1 sequence. This study uniquely demonstrates that altered binding to the RIPE3b1 sequence mediates glucose toxicity in betaTC-6 cells, thus reinforcing the importance of this cis-acting element in the regulation of insulin gene transcription. We conclude that the phenomenon of glucose toxicity decreasing binding of transcription factors and thereby reducing insulin gene expression is not a feature solely of HIT-T15 cells and may be demonstrable generally in beta-cell lines.
A Role of the Fast ATP-gated P2X1 Cation Channel in Thrombosis of Small Arteries In Vivo
Authors: Béatrice Hechler, Nadège Lenain, Patrizia Marchese, Catherine Vial, Véronique Heim, Monique Freund, Jean-Pierre Cazenave, Marco Cattaneo, Zaverio M. Ruggeri, Richard Evans, Christian Gachet
Journal: The Journal of Experimental Medicine (2003)

The P2X1 receptor is a fast ATP-gated cation channel expressed in blood platelets, where its role has been difficult to assess due to its rapid desensitization and the lack of pharmacological tools. In this paper, we have used P2X1−/− and wild-type mouse platelets, treated with apyrase to prevent desensitization, to demonstrate the function of P2X1 in the response to thrombogenic stimuli. In vitro, the collagen-induced aggregation and secretion of P2X1-deficient platelets was decreased, as was adhesion and thrombus growth on a collagen-coated surface, particularly when the wall shear rate was elevated. In vivo, the functional role of P2X1 could be demonstrated using two models of platelet-dependent thrombotic occlusion of small arteries, in which blood flow is characterized by a high shear rate. The mortality of P2X1−/− mice in a model of systemic thromboembolism was reduced and the size of mural thrombi formed after a laser-induced vessel wall injury was decreased as compared with normal mice, whereas the time for complete thrombus removal was shortened. Overall, the P2X1 receptor appears to contribute to the formation of platelet thrombi, particularly in arteries in which shear forces are high.
Cannabinoids and the gastrointestinal tract
Authors: R G PERTWEE
Journal: Gut (2001)

The enteric nervous system of several species, including the mouse, rat, guinea pig and humans, contains cannabinoid CB 1 receptors that depress gastrointestinal motility, mainly by inhibiting ongoing contractile transmitter release. Signs of this depressant effect are, in the whole organism, delayed gastric emptying and inhibition of the transit of non-absorbable markers through the small intestine and, in isolated strips of ileal tissue, inhibition of evoked acetylcholine release, peristalsis, and cholinergic and non-adrenergic non-cholinergic (NANC) contractions of longitudinal or circular smooth muscle. These are contractions evoked electrically or by agents that are thought to stimulate contractile transmitter release either in tissue taken from morphine pretreated animals (naloxone) or in unpretreated tissue (γ-aminobutyric acid and 5-hydroxytryptamine). The inhibitory effects of cannabinoid receptor agonists on gastric emptying and intestinal transit are mediated to some extent by CB 1 receptors in the brain as well as by enteric CB 1 receptors. Gastric acid secretion is also inhibited in response to CB 1 receptor activation, although the detailed underlying mechanism has yet to be elucidated. Cannabinoid receptor agonists delay gastric emptying in humans as well as in rodents and probably also inhibit human gastric acid secretion. Cannabinoid pretreatment induces tolerance to the inhibitory effects of cannabinoid receptor agonists on gastrointestinal motility. Findings that the CB 1 selective antagonist/inverse agonist SR141716A produces in vivo and in vitro signs of increased motility of rodent small intestine probably reflect the presence in the enteric nervous system of a population of CB 1 receptors that are precoupled to their effector mechanisms. SR141716A has been reported not to behave in this manner in the myenteric plexus-longitudinal muscle preparation (MPLM) of human ileum unless this has first been rendered cannabinoid tolerant. Nor has it been found to induce “withdrawal” contractions in cannabinoid tolerant guinea pig ileal MPLM. Further research is required to investigate the role both of endogenous cannabinoid receptor agonists and of non-CB 1 cannabinoid receptors in the gastrointestinal tract. The extent to which the effects on gastrointestinal function of cannabinoid receptor agonists or antagonists/inverse agonists can be exploited therapeutically has yet to be investigated as has the extent to which these drugs can provoke unwanted effects in the gastrointestinal tract when used for other therapeutic purposes.
Confusional Episodes and Antidepressant Medication
Authors: ROBERT K. DAVIES, GARY J. TUCKER, MARTIN HARROW, THOMAS P. DETRE
Journal: American Journal of Psychiatry (1971)

The authors studied confusional reactions in patients receiving antidepressants. The incidence of these reactions was significant; they occurred in 13 percent of the total sample and 35 percent of those over 40 years of age. The relationship to age was significant, but sex, prior EEG abnormality, and dosage did not seem to markedly affect the occurrence of the confusional reactions. The clinical picture was that of a toxic psychosis, and the reactions responded favorably to a decrease in dosage of the antidepressant and/or the addition of a phenothiazine, along with increased attention to environmental factors.
Cytogenetic Studies on the Mechanism of Formation of Isoantigenic Variants in Somatic Cell Hybrids. I. Banding Analyses of Isoantigenic Variant Sublines Derived From the Fusion of TA3Ha Carcinoma With MSWBS Sarcoma Cells2
Authors: F. Wiener, T. Dalianis, G. Klein, H. Harris
Journal: JNCI Journal of the National Cancer Institute (1974)

The MSWBS sarcoma, an isoantigenic loss variant selected from a near-diploid heterozygous tumor, lost one ofthe parental H-2 antigens by a mechanism that did not involve the loss of a whole chromosome bearing the relevant genetic determinant. But when the same selective procedures were used to select isoantigenic loss variants from hybrid cell tumors, loss of one parental H-2 antigen was associated with elimination of both chromosomes bearing that genetic determinant. This was established in an especially favorable hybrid line, TA3Ha/ MSWBS, in which both of the #17 chromosomes bearing the H-2 determinants derived from TA3Ha were morphologically normal, and both of the #17 chromosomes derived from MSWBS were involved in identifiable translocations.
Functional haplotypes of PADI4: relevance for rheumatoid arthritis specific synovial intracellular citrullinated proteins and anticitrullinated protein antibodies
Authors: T Cantaert
Journal: Annals of the Rheumatic Diseases (2005)

<b>Background:</b> Haplotypes of PADI4, encoding for a citrullinating enzyme, were associated with rheumatoid arthritis in a Japanese population. It was suggested they were related to the presence of anticitrullinated protein antibodies (ACPA). <b>Objective:</b> To explore the relation between PADI4 haplotypes, the presence of rheumatoid arthritis specific intracellular citrullinated proteins in synovial membrane, and serum ACPA titres. <b>Methods:</b> Synovial biopsies and peripheral blood samples were obtained in 59 patients with rheumatoid arthritis. Synovial intracellular citrullinated proteins were detected by immunohistochemistry. Serum ACPA titres were measured by anti-CCP2 ELISA. PADI4 haplotypes were determined by direct sequencing of the four exonic PADI4 single nucleotide polymorphisms. <b>Results:</b> PADI4 haplotype frequencies and the presence of synovial intracellular citrullinated proteins and ACPA were comparable with previous studies. There was no significant association between PADI4 haplotype 1 or 2 and the presence of synovial intracellular citrullinated proteins, although these proteins were associated with higher serum ACPA. There was no correlation between PADI4 haplotypes and serum ACPA, either by continuous analysis using the titres or by dichotomous analysis using the diagnostic cut off. Further analyses in homozygotes for haplotype 1 or 2 or in heterozygotes (1/2) also failed to show an association between PADI4 polymorphisms and ACPA. This contrasted with the clear association between ACPA levels and HLA-DR shared epitope. <b>Conclusions:</b> The link between synovial intracellular citrullinated proteins and ACPA emphasises the role of deimination of synovial proteins in rheumatoid arthritis, but the biological relevance of the PADI4 haplotypes for this autoimmune process is questionable, at least in a European population.
The incidence and prevalence of systemic lupus erythematosus in the UK, 1999–2012
Authors: Frances Rees, Michael Doherty, Matthew Grainge, Graham Davenport, Peter Lanyon, Weiya Zhang
Journal: Annals of the Rheumatic Diseases (2014)

To estimate the incidence and prevalence of systemic lupus erythematosus (SLE) in the UK over the period 1999-2012.A retrospective cohort study using the Clinical Practice Research Datalink (CPRD). The incidence was calculated per 100 000 person-years and the prevalence was calculated per 100 000 people for the period 1999-2012 and stratified by year, age group, gender, region and ethnicity. Three definitions of SLE were explored: (1) systemic lupus, (2) a fully comprehensive definition of lupus including cutaneous only lupus and (3) requiring supporting evidence of SLE in the medical record.Using our primary definition of SLE, the incidence during the study period was 4.91/100 000 person-years (95% CI 4.73 to 5.09), with an annual 1.8% decline (p<0.001). In contrast, the prevalence increased from 64.99/100 000 in 1999 (95% CI 62.04 to 67.93) (0.065%) to 97.04/100 000 in 2012 (95% CI 94.18 to 99.90) (0.097%). SLE was six times more common in women. The peak age of incidence was 50-59 years. There was regional variation in both incidence and prevalence. People of Black Caribbean ethnicity had the highest incidence and prevalence. Alternative definitions of SLE increased (definition 2) or decreased (definition 3) estimates of incidence and prevalence, but similar trends were found.The incidence of SLE has been declining but the prevalence has been increasing in the UK in recent years. Age, gender, region and ethnicity are risk factors for SLE. This is the first study to report ethnic differences on the incidence and prevalence of SLE using the CPRD.
Sex Differences in Lung Cancer Survival: Do Tumors Behave Differently in Elderly Women?
Authors: Juan P. Wisnivesky, Ethan A. Halm
Journal: Journal of Clinical Oncology (2007)

Women with lung cancer appear to have better survival. Whether this results from better response to treatment, different tumor biology, or a longer life expectancy is not well understood. This study sought to assess sex differences in the natural history of lung cancer after controlling for unrelated causes of death and type of treatment.This study included 18,967 elderly patients with stage I and II non-small-cell lung cancer diagnosed between 1991 and 1999 from the Surveillance, Epidemiology, and End Results registry linked to Medicare records. Patients were grouped into three categories according to the treatment received: surgery, radiation or chemotherapy but no surgery, and untreated cases. We used stratified and multivariate analyses to evaluate sex differences in survival using three methods to control for competing risks: lung cancer-specific survival, overall survival adjusting for comorbidities, and relative survival. Sensitivity analysis was used to test whether potential differences in smoking could account for the observed association of sex with survival.Women in all treatment groups had better lung cancer-specific, overall, and relative survival than did men (P < .0001). Stratified and multivariate analyses showed that women had better survival than did men after controlling for confounders. Sensitivity analyses showed that potential sex differences in smoking did not explain our findings.In this national, population-based sample, elderly women with early lung cancer had better risk-adjusted survival regardless of the type of treatment. That sex differences were observed among untreated patients suggests that lung cancer in women may have a different natural history.