tbuckley/cabot-search huggingface dataset:
Electrophysiologic Effects of Adenosine in Patients With Supraventricular Tachycardia
Authors: Kathryn A. Glatter, Jie Cheng, Parvin Dorostkar, Gunnard Modin, Sandeep Talwar, Marwan Al-Nimri, Randall J. Lee, Leslie A. Saxon, Michael D. Lesh, Melvin M. Scheinman
Journal: Circulation (1999)

We correlated the electrophysiologic (EP) effects of adenosine with tachycardia mechanisms in patients with supraventricular tachycardias (SVT).Adenosine was administered to 229 patients with SVTs during EP study: atrioventricular (AV) reentry (AVRT; n=59), typical atrioventricular node reentry (AVNRT; n=82), atypical AVNRT (n=13), permanent junctional reciprocating tachycardia (PJRT; n=12), atrial tachycardia (AT; n=53), and inappropriate sinus tachycardia (IST; n=10). There was no difference in incidence of tachycardia termination at the AV node in AVRT (85%) versus AVNRT (86%) after adenosine, but patients with AVRT showed increases in the ventriculoatrial (VA) intervals (13%) compared with typical AVNRT (0%), P<0.005. Changes in atrial, AV, or VA intervals after adenosine did not predict the mode of termination of long R-P tachycardias. For patients with AT, there was no correlation with location of the atrial focus and adenosine response. AV block after adenosine was only observed in AT patients (27%) or IST (30%). Patients with IST showed atrial cycle length increases after adenosine (P<0.05) with little change in activation sequence. The incidence of atrial fibrillation after adenosine was higher for those with AVRT (15%) compared with typical AVNRT (0%) P<0.001, or atypical AVNRT (0%) but similar to those with AT (11%) and PJRT (17%).The EP response to adenosine proved of limited value to identify the location of AT or SVT mechanisms. Features favoring AT were the presence of AV block or marked shortening of atrial cycle length before tachycardia suppression. Atrial fibrillation was more common after adenosine in patients with AVRT, PJRT, or AT. Patients with IST showed increases in cycle length with little change in atrial activation sequence after adenosine.
Smaller Frontal Gray Matter Volume in Postmortem Schizophrenic Brains
Authors: Lynn D. Selemon, Joel E. Kleinman, Mary M. Herman, Patricia S. Goldman-Rakic
Journal: American Journal of Psychiatry (2002)

The prefrontal cortex exhibits prominent functional, biochemical, and anatomic abnormalities in schizophrenic patients. However, smaller than normal volume of the frontal lobe has not been found in previous postmortem studies of schizophrenic subjects, and magnetic resonance imaging (MRI) scans of schizophrenic subjects have not consistently revealed frontal volumetric deficits. The variability in MRI findings may be related partly to difficulty in defining the posterior border of the frontal lobe. In this study, precise measurements of frontal lobe volume from postmortem brains were derived by defining the posterior border according to the brain atlas of Talairach and Tournoux and by applying stereologic methods to estimate gray and white matter volumes.Whole, or nearly whole, formalin-fixed left hemispheres from 14 schizophrenic and 19 normal comparison subjects were analyzed. Total cortical gray and white matter volumes, as well as frontal cortical gray and white matter volumes, were measured by using the Cavalieri method.Only frontal gray matter volume was significantly smaller in the schizophrenic subjects than in the comparison subjects (12% difference). The differences between groups in total gray and white matter volumes and frontal white matter volume (6%-8% smaller in the schizophrenic subjects than in the comparison subjects) did not reach statistical significance.The smaller frontal gray matter volume observed in schizophrenic brains suggests that pathology of the frontal lobe may be more severe than that of the three posterior lobes and may account for the prominence of prefrontal dysfunction associated with schizophrenia.
Novel Chemical Enhancers of Heat Shock Increase Thermal Radiosensitization through a Mitotic Catastrophe Pathway
Authors: Konjeti R. Sekhar, Vijayakumar N. Sonar, Venkatraj Muthusamy, Soumya Sasi, Andrei Laszlo, Jamil Sawani, Nobuo Horikoshi, Ryuji Higashikubo, Robert G. Bristow, Michael J. Borrelli, Peter A. Crooks, James R. Lepock, Joseph L. Roti Roti, Michael L. Freeman
Journal: Cancer Research (2007)

Abstract Radiation therapy combined with adjuvant hyperthermia has the potential to provide outstanding local-regional control for refractory disease. However, achieving therapeutic thermal dose can be problematic. In the current investigation, we used a chemistry-driven approach with the goal of designing and synthesizing novel small molecules that could function as thermal radiosensitizers. (Z)-(±)-2-(1-Benzenesulfonylindol-3-ylmethylene)-1-azabicyclo[2.2.2]octan-3-ol was identified as a compound that could lower the threshold for Hsf1 activation and thermal sensitivity. Enhanced thermal sensitivity was associated with significant thermal radiosensitization. We established the structural requirements for activity: the presence of an N-benzenesulfonylindole or N-benzylindole moiety linked at the indolic 3-position to a 2-(1-azabicyclo[2.2.2]octan-3-ol) or 2-(1-azabicyclo[2.2.2]octan-3-one) moiety. These small molecules functioned by exploiting the underlying biophysical events responsible for thermal sensitization. Thermal radiosensitization was characterized biochemically and found to include loss of mitochondrial membrane potential, followed by mitotic catastrophe. These studies identified a novel series of small molecules that represent a promising tool for the treatment of recurrent tumors by ionizing radiation. [Cancer Res 2007;67(2):695–701]
Sleepwalking Violence: A Sleep Disorder, a Legal Dilemma, and a Psychological Challenge
Authors: Rosalind Cartwright
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: The purpose of this article is to further an understanding of the psychological state when aggression follows an episode of partial arousal from early non-REM sleep during which some areas of the brain appear to be functioning as in waking while others appear to remain in a state of sleep. To illustrate this, the author examines a case of homicide for which the defense argued lack of responsibility due to sleepwalking. METHOD: A review of the forensic literature on sleepwalking aggression and sleep studies suggests that these fall into one or both of two DSM-IV-TR diagnoses: sleepwalking disorder and sleep terror disorder. The new case, which would meet criteria for an overlap disorder in which sleepwalking is followed by sleep terror, is compared to one previously published. RESULTS: These findings support sleepwalking violence as a distinct overlap disorder with common disturbed psychological functioning during and for a period up to 1 hour following an aggressive episode. CONCLUSIONS: Research clarifies the pathology of this disorder and highlights the need to both refine the differential diagnosis and test the efficacy of treatment protocols.
Predominant role for C5b-9 in renal ischemia/reperfusion injury
Authors: Wuding Zhou, Conrad A. Farrar, Katsushige Abe, Julian R. Pratt, James E. Marsh, Yi Wang, Gregory L. Stahl, Steven H. Sacks
Journal: Journal of Clinical Investigation (2000)

Previous work has indicated that complement is a mediator of ischemia/reperfusion (I/R) injury. To investigate the components of complement responsible for this effect, we examined a model of renal I/R injury in C3-, C4-, C5-, and C6-deficient mice. We occluded the renal arteries and veins (40–58 minutes) and, after reperfusion (0–72 hours), assessed renal structural and functional injury. C3-, C5-, and C6-deficient mice were protected from renal I/R injury, whereas C4-deficient mice were not protected. C6-deficient mice treated with antibody to block C5a generation showed no additional protection from I/R injury. Reconstitution with C6 alone restored the I/R injury in C6-deficient mice. Tubular epithelial cells were the main structures damaged by complement-mediated attack, and, in contrast, the renal vessels were spared. Neutrophil infiltration and myeloperoxidase activity were reduced in C-deficient mouse kidney, but by a similar extent in C3-deficient and C6-deficient mice. We conclude that the membrane attack complex of complement (in which C5 and C6 participate) may account for the effect of complement on mouse renal I/R injury. Neither C5a-mediated neutrophil infiltration nor the classic pathway, in which C4 participates, appears to contribute to I/R injury in this model. By contrast with other organs, such as the heart, the primary effect of complement in the ischemic area is on the parenchymal cell rather than the vascular endothelial cell. The membrane attack complex of complement is a potential target for prevention of I/R injury in this model.
Enhanced Foam Cell Formation, Atherosclerotic Lesion Development, and Inflammation by Combined Deletion of ABCA1 and SR-BI in Bone Marrow–Derived Cells in LDL Receptor Knockout Mice on Western-Type Diet
Authors: Ying Zhao, Marieke Pennings, Reeni B. Hildebrand, Dan Ye, Laura Calpe-Berdiel, Ruud Out, Martin Kjerrulf, Eva Hurt-Camejo, Albert K. Groen, Menno Hoekstra, Wendy Jessup, Giovanna Chimini, Theo J.C. Van Berkel, Miranda Van Eck
Journal: Circulation Research (2010)

macrophages cannot limit the uptake of lipids and rely on cholesterol efflux mechanisms for maintaining cellular cholesterol homeostasis. Important mediators of macrophage cholesterol efflux are ATP-binding cassette transporter 1 (ABCA1), which mediates the efflux of cholesterol to lipid-poor apolipoprotein AI, and scavenger receptor class B type I (SR-BI), which promotes efflux to mature high-density lipoprotein.the aim of the present study was to increase the insight into the putative synergistic roles of ABCA1 and SR-BI in foam cell formation and atherosclerosis.low-density lipoprotein receptor knockout (LDLr KO) mice were transplanted with bone marrow from ABCA1/SR-BI double knockout mice, the respective single knockouts, or wild-type littermates. Serum cholesterol levels were lower in ABCA1/SR-BI double knockout transplanted animals, as compared to the single knockout and wild-type transplanted animals on Western-type diet. Despite the lower serum cholesterol levels, massive foam cell formation was found in macrophages from spleen and the peritoneal cavity. Interestingly, ABCA1/SR-BI double knockout transplanted animals also showed a major increase in proinflammatory KC (murine interleukin-8) and interleukin-12p40 levels in the circulation. Furthermore, after 10 weeks of Western-type diet feeding, atherosclerotic lesion development in the aortic root was more extensive in the LDLr KO mice reconstituted with ABCA1/SR-BI double knockout bone marrow.deletion of ABCA1 and SR-BI in bone marrow-derived cells enhances in vivo macrophage foam cell formation and atherosclerotic lesion development in LDLr KO mice on Western diet, indicating that under high dietary lipid conditions, both macrophage ABCA1 and SR-BI contribute significantly to cholesterol homeostasis in the macrophage in vivo and are essential for reducing the risk for atherosclerosis.
Epidermal Growth Factor Receptor Variant III Contributes to Cancer Stem Cell Phenotypes in Invasive Breast Carcinoma
Authors: Catherine A. Del Vecchio, Kristin C. Jensen, Ryan T. Nitta, A. Hunter Shain, Craig P. Giacomini, Albert J. Wong
Journal: Cancer Research (2012)

EGFRvIII is a tumor-specific variant of the epidermal growth factor receptor (EGFR). Although EGFRvIII is most commonly found in glioblastoma, its expression in other tumor types remains controversial. In this study, we investigated EGFRvIII expression and amplification in primary breast carcinoma. Our analyses confirmed the presence of EGFRvIII, but in the absence of amplification or rearrangement of the EGFR locus. Nested reverse transcriptase PCR and flow cytometry were used to detect a higher percentage of positive cases. EGFRvIII-positive cells showed increased expression of genes associated with self-renewal and epithelial-mesenchymal transition along with a higher percentage of stem-like cells. EGFRvIII also increased in vitro sphere formation and in vivo tumor formation. Mechanistically, EGFRvIII mediated its effects through the Wnt/β-catenin pathway, leading to increased β-catenin target gene expression. Inhibition of this pathway reversed the observed effects on cancer stem cell (CSC) phenotypes. Together, our findings show that EGFRvIII is expressed in primary breast tumors and contributes to CSC phenotypes in breast cancer cell lines through the Wnt pathway. These data suggest a novel function for EGFRvIII in breast tumorigenesis.
Clinical features of dominant and recessive interferon γ receptor 1 deficiencies
Authors: Susan E Dorman, Capucine Picard, David Lammas, Klaus Heyne, Jaap T van Dissel, Richard Baretto, Sergio D Rosenzweig, Melanie Newport, Michael Levin, Joachim Roesler, Dinakantha Kumararatne, Jean-Laurent Casanova, Steven M Holland
Journal: The Lancet (2004)
Upregulation of Periostin and Reactive Stroma Is Associated with Primary Chemoresistance and Predicts Clinical Outcomes in Epithelial Ovarian Cancer
Authors: Lisa Ryner, Yinghui Guan, Ron Firestein, Yuanyuan Xiao, Younjeong Choi, Christina Rabe, Shan Lu, Eloisa Fuentes, Ling-Yuh Huw, Mark R. Lackner, Ling Fu, Lukas C. Amler, Carlos Bais, Yulei Wang
Journal: Clinical Cancer Research (2015)

Up to one third of ovarian cancer patients are intrinsically resistant to platinum-based treatment. However, predictive and therapeutic strategies are lacking due to a poor understanding of the underlying molecular mechanisms. This study aimed to identify key molecular characteristics that are associated with primary chemoresistance in epithelial ovarian cancers.Gene expression profiling was performed on a discovery set of 85 ovarian tumors with clinically well-defined response to chemotherapies as well as on an independent validation dataset containing 138 ovarian patients from the chemotreatment arm of the ICON7 trial.We identified a distinct "reactive stroma" gene signature that is specifically associated with primary chemoresistant tumors and was further upregulated in posttreatment recurrent tumors. Immunohistochemistry (IHC) and RNA in situ hybridization (RNA ISH) analyses on three of the highest-ranked signature genes (POSTN, LOX, and FAP) confirmed that modulation of the reactive stroma signature genes within the peritumoral stromal compartments was specifically associated with the clinical chemoresistance. Consistent with these findings, chemosensitive ovarian cells grown in the presence of recombinant POSTN promoted resistance to carboplatin and paclitaxel treatment in vitro. Finally, we validated the reactive stroma signature in an independent dataset and demonstrated that a high POSTN expression level predicts shorter progression-free survival following first-line chemotherapy.Our findings highlight the important interplay between cancer and the tumor microenvironment in ovarian cancer biology and treatment. The identified reactive stromal components in this study provide a molecular basis to the further development of novel diagnostic and therapeutic strategies for overcoming chemoresistance in ovarian cancer.
High Dose Trifluoperazine Therapy in Chronic Schizophrenia
Authors: ROBERT F. PRIEN, JEROME LEVINE, JONATHAN O. COLE
Journal: American Journal of Psychiatry (1969)

This collaborative study on the efficacy of high doses of trifluoperazine in chronic schizophrenia showed that treatment response was related to length of hospitalization; short-term patients benefited most. High doses of trifluoperazine were most effective with those short-term patients who had been on a piperazine phenothiazine prior to the study. Also, most placebo patients who had been receiving low doses of phenothiazines before the study did not suffer deleterious effects while they were off medication. Treatment implications are discussed.
Difficult Conversations in Medicine
Authors: Nick Dunn
Journal: Journal of the Royal Society of Medicine (2005)

To a greater or lesser extent, nearly all medical conversations can become 'difficult': there is always an element of unpredictability, and the more one listens to the patient the more one can become led off the comfortable, well-trodden path. 'Why do doctors find it difficult to listen?' asks this book very early on: time restraints are one excuse, but I suspect a feeling of loss of control may well be another. The book is an attempt to allow doctors to remain in control while still addressing the patient's (or other healthworker's) concerns as comprehensively as possible. This is not an easy agenda and it is to the editor's credit that she has managed to assemble authors who tackle the subject in an approachable and interesting way.

The book starts with the basis of good communication and works its way through most of the special situations that one can imagine—children, elderly, dying and bereavement, strong emotions, different cultural groups, failing colleagues and so on. There is a wealth of good advice, in many cases well illustrated by specific examples. At the end there is an appendix of transcripts of examples of actual conversations, which is particularly useful and is also a lively read.

The book is very much aimed at junior doctors in the hospital setting, and needs to be seen within that constraint. For example, there is very little input specifically from a primary care perspective, although much of the content is, of course, relevant. I would have liked to see something on how to deal with issues such as underage contraception, termination of pregnancy and poor communication between hospital and general practitioner. It is also disappointing that the chapter on 'Communication in a multiprofessional setting' does not acknowledge the importance of establishing strong channels of communication between primary and secondary care when dealing with patients with terminal illness, for example. Many embarrassing misunderstandings are caused simply by failure of colleagues to talk to each other or to fully inform the patient of the management plan. Some contributions sit uneasily with the title; for example, a chapter advising doctors on how to avoid 'burn-out' seems out of place and is somewhat trite. Nevertheless, this book is a really useful addition to the published work on communication skills and how this affects the doctor–patient relationship. It deserves to be widely read, especially by young doctors but also by students, consultants and GPs, all of whom might be spared sleepless nights mulling over conversations that somehow went wrong.
Selective targeting of activated T cells in chronic intestinal inflammation
Authors: B. Weigmann, M. F Neurath
Journal: Gut (2009)

Programmed cell death (apoptosis) has been implicated in normal biological processes as well as in the pathology of human diseases.1 The characterisation of genes involved in apoptosis has been pursued intensively and led to the identification of two major classes of genes: the bcl-2 family and the caspase family. Caspases are proteases that cleave their target substrates at specific peptide sequences and during apoptosis the activation of caspases takes place in a cascade fashion, leading to nuclear engulfment and cell death. Thus, caspases represent key functional components of the apoptosis pathway in human cells.

Resistance against apoptosis is a key phenomenon in various chronic inflammatory diseases as well as cancer.2–4 In the immune system, it has been shown that T cell resistance against apoptosis may contribute for the perpetuation of inflammatory processes such as seen in patients with inflammatory bowel diseases.5 6 This resistance of T cells against programmed cell death is probably driven by proinflammatory cytokines such as interleukin 6 (IL6).7 However, the functional relevance of T cell resistance against apoptosis is highlighted by the finding that induction of T cell death is likely related to the therapeutic efficacy of anti-tumour necrosis factor (TNF) antibodies in patients with inflammatory bowel diseases. …
Prediction model of hepatocarcinogenesis for patients with hepatitis C virus-related cirrhosis. Validation with internal and external cohorts
Authors: Kenji Ikeda, Yasuji Arase, Satoshi Saitoh, Masahiro Kobayashi, Takashi Someya, Tetsuya Hosaka, Norio Akuta, Yoshiyuki Suzuki, Fumitaka Suzuki, Hitomi Sezaki, Hiromitsu Kumada, Akihisa Tanaka, Hideharu Harada
Journal: Journal of Hepatology (2006)
The effect of biological agents on work participation in rheumatoid arthritis patients: a systematic review
Authors: M M ter Wee, W F Lems, H Usan, A Gulpen, A Boonen
Journal: Annals of the Rheumatic Diseases (2011)

This study reviewed the effect of biological agents on participation in paid work among patients with rheumatoid arthritis (RA). A systematic literature search was performed to identify published articles reporting the effect of biological agents on employment status, sick leave and/or presenteeism. The quality of included articles was assessed according to the guidelines as proposed by the Dutch Cochrane Centre. Narrative summaries were used to present the data separately for randomised controlled trials (RCTs) as well as controlled and uncontrolled cohort studies. 19 studies (six uncontrolled cohorts, seven controlled cohorts and six RCTs) were included, in which 11 259 patients were treated with biological agents. Employment status improved in four out of 13 studies, absence from work in all 10 studies and presenteeism in seven out of nine studies that reported this outcome. For absenteeism and presenteeism the statistical significance of change or difference was not always provided and results within studies were sometimes conflicting when using different time frames or alternative outcomes. The large heterogeneity in terms of population, design, analyses and most important in outcome measures limits interpretation of the data. RCTs as well as cohort studies showed positive results of biological agents on both absenteeism and presenteeism compared with other disease-modifying antirheumatic drugs (DMARD), continuing the failing DMARD, the general population or the situation before the start of biological agents. The effect on employment status was more conflicting, but 50% of studies that addressed patients with early methotrexate-naive RA showed a positive result on employment status.
The role of gut microbiota (commensal bacteria) and the mucosal barrier in the pathogenesis of inflammatory and autoimmune diseases and cancer: contribution of germ-free and gnotobiotic animal models of human diseases
Authors: Helena Tlaskalová-Hogenová, Renata Štěpánková, Hana Kozáková, Tomáš Hudcovic, Luca Vannucci, Ludmila Tučková, Pavel Rossmann, Tomáš Hrnčíř, Miloslav Kverka, Zuzana Zákostelská, Klára Klimešová, Jaroslava Přibylová, Jiřina Bártová, Daniel Sanchez, Petra Fundová, Dana Borovská, Dagmar Šrůtková, Zdeněk Zídek, Martin Schwarzer, Pavel Drastich, David P Funda
Journal: Cellular and Molecular Immunology (2011)