tbuckley/cabot-search huggingface dataset:
Multiple clinical and biological autoimmune manifestations in 50 workers after occupational exposure to silica.
Authors: J Sanchez-Roman, I Wichmann, J Salaberri, J M Varela, A Nunez-Roldan
Journal: Annals of the Rheumatic Diseases (1993)

OBJECTIVES--A self referred group of four workers from a factory producing scouring powder with a high silica content showed a surprisingly high number of features compatible with a connective tissue disease. Further subjects working at the same factory were subsequently studied to evaluate the relation between this exposure and the development of autoimmune processes. METHODS--A total of 50 subjects (44 women, six men; mean (SD) age 43.7 (5.5) years; mean duration of employment 6.1 years) underwent a prospective study including clinical history and physical examination, an immunobiological study, HLA typing, radiological and functional oesophageal and respiratory examination, ophthalmological examination, and isotopic testing of salivary glands. RESULTS--Symptoms of a systemic illness were present in 32 (64%) subjects: six with Sjögren9s syndrome; five with the criteria for systemic sclerosis; three with systemic lupus erythematosus (SLE); five with an 9overlap syndrome9; and 13 with undifferentiated findings not meeting the criteria for a defined disease. Antinuclear antibodies were present in 36 (72%) subjects; four had antibodies to native DNA, including two subjects with SLE, one with systemic sclerosis associated with secondary Sjögren9s syndrome, and one with overlap syndrome. Anticentromere antibodies were not detected. The frequency of HLA-DR3 was increased in the clinically affected subjects, but did not reach statistical significance. CONCLUSIONS--This descriptive study emphasises the high probability of workers occupationally exposed to silica developing a multiple spectrum of clinical and serological autoimmune manifestations.
β-Arrestin1 mediates nicotinic acid–induced flushing, but not its antilipolytic effect, in mice
Authors: Robert W. Walters, Arun K. Shukla, Jeffrey J. Kovacs, Jonathan D. Violin, Scott M. DeWire, Christopher M. Lam, J. Ruthie Chen, Michael J. Muehlbauer, Erin J. Whalen, Robert J. Lefkowitz
Journal: Journal of Clinical Investigation (2009)

Nicotinic acid is one of the most effective agents for both lowering triglycerides and raising HDL. However, the side effect of cutaneous flushing severely limits patient compliance. As nicotinic acid stimulates the GPCR GPR109A and Gi/Go proteins, here we dissected the roles of G proteins and the adaptor proteins, beta-arrestins, in nicotinic acid-induced signaling and physiological responses. In a human cell line-based signaling assay, nicotinic acid stimulation led to pertussis toxin-sensitive lowering of cAMP, recruitment of beta-arrestins to the cell membrane, an activating conformational change in beta-arrestin, and beta-arrestin-dependent signaling to ERK MAPK. In addition, we found that nicotinic acid promoted the binding of beta-arrestin1 to activated cytosolic phospholipase A2 as well as beta-arrestin1-dependent activation of cytosolic phospholipase A2 and release of arachidonate, the precursor of prostaglandin D2 and the vasodilator responsible for the flushing response. Moreover, beta-arrestin1-null mice displayed reduced cutaneous flushing in response to nicotinic acid, although the improvement in serum free fatty acid levels was similar to that observed in wild-type mice. These data suggest that the adverse side effect of cutaneous flushing is mediated by beta-arrestin1, but lowering of serum free fatty acid levels is not. Furthermore, G protein-biased ligands that activate GPR109A in a beta-arrestin-independent fashion may represent an improved therapeutic option for the treatment of dyslipidemia.
Persistent Genital Human Papillomavirus Infection as a Risk Factor for Persistent Cervical Dysplasia
Authors: G. Y. F. Ho, R. D. Burk, S. Klein, A. S. Kadish, C. J. Chang, P. Palan, J. Basu, R. Tachezy, R. Lewis, S. Romney
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Persistent Genital Human Papillomavirus Infection as a Risk Factor for Persistent Cervical Dysplasia Get access Gloria Y. F. Ho, Gloria Y. F. Ho Department of Epidemiology and Social Medicine, Albert Einstein College of MedicineBronx, NY Correspondence to : Gloria Y. F. Ho, Ph.D., Department of Epidemiology and Social Medicine, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461. Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert D. Burk, Robert D. Burk Department of Pediatrics, Department of Obstetrics and Gynecology, and Department of Microbiology and Immunology, Albert Einstein College of MedicineBronx, NY Search for other works by this author on: Oxford Academic PubMed Google Scholar Sara Klein, Sara Klein Department of Obstetrics and Gynecology, Albert Einstein College of MedicineBronx, NY Search for other works by this author on: Oxford Academic PubMed Google Scholar Anna S. Kadish, Anna S. Kadish Department of Pathology, Albert Einstein College of MedicineBronx, NY Search for other works by this author on: Oxford Academic PubMed Google Scholar C. J. Chang, C. J. Chang Department of Epidemiology and Social Medicine, Albert Einstein College of MedicineBronx, NY Search for other works by this author on: Oxford Academic PubMed Google Scholar Prabhudas Palan, Prabhudas Palan Department of Obstetrics and Gynecology, Albert Einstein College of MedicineBronx, NY Search for other works by this author on: Oxford Academic PubMed Google Scholar Jayasri Basu, Jayasri Basu Department of Obstetrics and Gynecology, Albert Einstein College of MedicineBronx, NY Search for other works by this author on: Oxford Academic PubMed Google Scholar Ruth Tachezy, Ruth Tachezy Department of Microbiology and Immunology, Albert Einstein College of MedicineBronx, NY Search for other works by this author on: Oxford Academic PubMed Google Scholar Renee Lewis, Renee Lewis Department of Microbiology and Immunology, Albert Einstein College of MedicineBronx, NY Search for other works by this author on: Oxford Academic PubMed Google Scholar Seymour Romney Seymour Romney Department of Obstetrics and Gynecology, Albert Einstein College of MedicineBronx, NY Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 18, 20 September 1995, Pages 1365–1371, https://doi.org/10.1093/jnci/87.18.1365 Published: 20 September 1995 Article history Received: 27 October 1994 Revision received: 02 June 1995 Accepted: 03 July 1995 Published: 20 September 1995
Systemic Anthrax Lethal Toxin Therapy Produces Regressions of Subcutaneous Human Melanoma Tumors in Athymic Nude Mice
Authors: Ralph J. Abi-Habib, Ravibhushan Singh, Stephen H. Leppla, John J. Greene, Yan Ding, Bree Berghuis, Nicholas S. Duesbery, Arthur E. Frankel
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Anthrax Lethal Toxin (LeTx), composed of protective antigen and lethal factor, catalytically cleaves mitogen-activated protein kinase (MAPK) kinases and inhibits the MAPK signaling pathways. The majority of metastatic melanomas possess the V599E BRAF mutation, which constitutively activates MAPK1/2 signaling. LeTx is cytotoxic to BRAF mutant melanoma cell lines in vitro, whereas most normal cells are resistant to this toxin. In this study, we determine the in vivo potency and safety of systemically administered LeTx. Experimental Design: A s.c. xenograft melanoma model in athymic nude mice was treated with different i.p. doses of LeTx. Results: In this study, we show that in vivo systemic LeTx treatment of s.c. xenograft melanoma tumors in athymic nude mice yields partial and complete tumor regressions with minor toxicity to mice. When animal toxicity was observed, we did not find any histologic evidence of tissue damage. Conclusions: LeTx is one of the rare targeted agents to produce complete remissions of human melanomas in an animal model and thus warrants further preclinical development.
Glycogen Synthase Kinase-3β Participates in Nuclear Factor κB–Mediated Gene Transcription and Cell Survival in Pancreatic Cancer Cells
Authors: Andrei V. Ougolkov, Martin E. Fernandez-Zapico, Doris N. Savoy, Raul A. Urrutia, Daniel D. Billadeau
Journal: Cancer Research (2005)

Abstract Recent studies using glycogen synthase kinase-3β (GSK-3β)–deficient mouse embryonic fibroblasts suggest that GSK-3β positively regulates nuclear factor κB (NFκB)–mediated gene transcription. Because NFκB is suggested to participate in cell proliferation and survival pathways in pancreatic cancer, we investigated the role of GSK-3β in regulating these cellular processes. Herein, we show that pancreatic cancer cells contain a pool of active GSK-3β and that pharmacologic inhibition of GSK-3 kinase activity using small molecule inhibitors or genetic depletion of GSK-3β by RNA interference leads to decreased cancer cell proliferation and survival. Mechanistically, we show that GSK-3β influences NFκB-mediated gene transcription at a point distal to the Iκ kinase complex, as only ectopic expression of the NFκB subunits p65/p50, but not an Iκ kinase β constitutively active mutant, could rescue the decreased cellular proliferation and survival associated with GSK-3β inhibition. Taken together, our results simultaneously identify a previously unrecognized role for GSK-3β in cancer cell survival and proliferation and suggest GSK-3β as a potential therapeutic target in the treatment of pancreatic cancer.
PIGMENTATION AND TRANSPLANTATION.
Authors: Alfred Fessler
Journal: British Journal of Dermatology (1941)

Journal Article PIGMENTATION AND TRANSPLANTATION. Get access ALFRED FESSLER ALFRED FESSLER Institute of Pathology, Queen's University, Belfast Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 53, Issue 7, 1 July 1941, Pages 201–214, https://doi.org/10.1111/j.1365-2133.1941.tb10915.x Published: 01 July 1941
The Th17 Pathway and Inflammatory Diseases of the Intestines, Lungs, and Skin
Authors: Casey T. Weaver, Charles O. Elson, Lynette A. Fouser, Jay K. Kolls
Journal: Annual Review of Pathology Mechanisms of Disease (2011)

The recent discovery of a new CD4 + T cell subset, Th17, has transformed our understanding of the pathogenetic basis of an increasing number of chronic immune-mediated diseases. Particularly in tissues that interface with the microbial environment—such as the intestinal and respiratory tracts and the skin—where most of the Th17 cells in the body reside, dysregulated immunity to self (or the extended self, the diverse microbiota that normally colonize these tissues) can result in chronic inflammatory disease. In this review, we focus on recent advances in the biology of the Th17 pathway and on genome-wide association studies that implicate this immune pathway in human disease involving these tissues.
Paired Electrical Stimulation and the Maximal Contractile Response of the Ventricle
Authors: VINCENT J. FISHER, ROBERT J. LEE, ANTHONY M. MARLON, FREDERIC KAVALER
Journal: Circulation Research (1967)

Paired stimulation of the isometrically contracting papillary muscle of the cat caused it to develop 80 to 100% of the tension it develops in a high calcium, low sodium medium. The isovolumic left ventricle of the dog responded to paired stimuli with a significant increase in developed pressure and in maximal rate of rise of pressure (dP/dt max) at all ventricular volumes. During stimulation of the isovolumic left ventricle, there was little or no further potentiation induced by norepinephrine or calcium gluconate infusion. Paired stimulation is thus capable of inducing a maximal or near-maximal contractility of ventricular muscle at any given ventricular volume. Using dP/dt max as an index of left ventricular contractile force which is relatively uninfluenced by aortic afterloading, paired stimulation was found to cause significant potentiation in the ejecting left ventricle (64% increase above control dP/dt max). Unlike the papillary muscle and the isovolumic ventricle, the combination of paired stimulation and norepinephrine infusion caused a further increase in dP/dt max of the ejecting left ventricle. This may be explainable by the increase in ventricular size caused by norepinephrine, but in some instances norepinephrine added to the inotropic effects of paired stimulation.
Myocardial Dysfunction With Coronary Microembolization
Authors: Matthias Thielmann, Hilmar Dörge, Claus Martin, Sergej Belosjorow, Uwe Schwanke, Anita van de Sand, Ina Konietzka, Astrid Büchert, Arne Krüger, Rainer Schulz, Gerd Heusch
Journal: Circulation Research (2002)

Coronary microembolization results in progressive myocardial dysfunction, with causal involvement of tumor necrosis factor-α (TNF-α). TNF-α uses a signal transduction involving nitric oxide (NO) and/or sphingosine. Therefore, we induced coronary microembolization in anesthetized dogs and studied the role and sequence of NO, TNF-α, and sphingosine for the evolving contractile dysfunction. Four sham-operated dogs served as controls (group 1). Eleven dogs received placebo (group 2), 6 dogs received the NO synthase inhibitor N G -nitro- l -arginine methyl ester (L-NAME, group 3), and 6 dogs received the ceramidase inhibitor N -oleoylethanolamine (NOE, group 4) before microembolization was induced by infusion of 3000 microspheres (42-μm diameter) per milliliter inflow into the left circumflex coronary artery. Posterior systolic wall thickening (PWT) remained unchanged in group 1 but decreased progressively in group 2 from 20.6±4.9% (mean±SD) at baseline to 4.1±3.7% at 8 hours after microembolization. Leukocyte count, TNF-α, and sphingosine contents were increased in the microembolized posterior myocardium. In group 3, PWT remained unchanged (20.3±2.6% at baseline) with intracoronary administration of L-NAME (20.8±3.4%) and 17.7±2.3% at 8 hours after microembolization; TNF-α and sphingosine contents were not increased. In group 4, PWT also remained unchanged (20.7±4.6% at baseline) with intravenous administration of NOE (19.5±5.7%) and 16.4±6.3% at 8 hours after microembolization; TNF-α, but not sphingosine content, was increased. In all groups, systemic hemodynamics, anterior systolic wall thickening, and regional myocardial blood flow remained unchanged throughout the protocols. A signal transduction cascade of NO, TNF-α, and sphingosine is causally involved in the coronary microembolization-induced progressive contractile dysfunction.
Thrombolysis for acute submassive pulmonary embolism: CON viewpoint
Authors: A John Simpson
Journal: Thorax (2013)

The normotensive patient with confirmed pulmonary embolism (PE) and right ventricular (RV) dilatation presents a significant dilemma to clinicians. On one hand, a string of publications have demonstrated that RV dysfunction is associated with adverse outcomes in patients with PE;1–5 on the other, thrombolysis carries a significant risk of bleeding.6 ,7 However, evidence emerging in recent years has provided a strong case against using thrombolysis in this setting, greatly aiding clinical decision-making in submassive PE (taken here to mean confirmed PE in a normotensive patient with evidence of RV dilatation and/or RV dysfunction and/or pulmonary hypertension). The aim of this article is to review some of the most important data surrounding this debate.

The decision to administer systemic thrombolysis would be easier if submassive PE had a high mortality rate that was significantly reduced by treatment. However, this is not the case. In larger studies, inhospital or 30-day mortality for submassive PE treated without thrombolysis is typically between 1% and 5%,3 ,8–11 though lower and higher rates have been described.12–14 In the excellent, landmark randomised controlled trial (RCT) of thrombolysis versus heparin alone for submassive PE, mortality was 3.4% in the thrombolysed group and 2.2% in the ‘heparin-alone’ group.8 The argument is commonly made that trials exclude elderly patients or patients with comorbidities, artificially reducing mortality rates. However, the large RIETE registry also suggests a 90-day mortality of around 3% in patients with submassive PE.15 The problem for advocates of thrombolysis in PE is that it may be technically impossible to demonstrate beneficial effects on mortality. This is because an RCT comparing thrombolysis and standard treatment would require prohibitively large numbers of patients to generate sufficient statistical power to detect a clinically meaningful difference in mortality.

Faced with this problem, those who …
An endoscopic pancreatic function test with cholecystokinin-octapeptide for the diagnosis of chronic pancreatitis
Authors: Darwin L. Conwell, Gregory Zuccaro, John J. Vargo, J.Brad Morrow, Nancy Obuchowski, John A. Dumot, Patricia A. Trolli, Allison Burton, Cathy O'Laughlin, Frederick Van Lente
Journal: Clinical Gastroenterology and Hepatology (2003)
Intravenous RNA Interference Gene Therapy Targeting the Human Epidermal Growth Factor Receptor Prolongs Survival in Intracranial Brain Cancer
Authors: Yun Zhang, Yu-feng Zhang, Joshua Bryant, Andrew Charles, Ruben J. Boado, William M. Pardridge
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The human epidermal growth factor receptor (EGFR) plays an oncogenic role in solid cancer, including brain cancer. The present study was designed to prolong survival in mice with intracranial human brain cancer with the weekly i.v. injection of nonviral gene therapy causing RNA interference (RNAi) of EGFR gene expression. Experimental Design: Human U87 gliomas were implanted in the brain of adult scid mice, and weekly i.v. gene therapy was started at day 5 after implantation of 500,000 cells. An expression plasmid encoding a short hairpin RNA directed at nucleotides 2529–2557 within the human EGFR mRNA was encapsulated in pegylated immunoliposomes. The pegylated immunoliposome was targeted to brain cancer with 2 receptor-specific monoclonal antibodies (MAb), the murine 83–14 MAb to the human insulin receptor and the rat 8D3 MAb to the mouse transferrin receptor. Results: In cultured glioma cells, the delivery of the RNAi expression plasmid resulted in a 95% suppression of EGFR function, based on measurement of thymidine incorporation or intracellular calcium signaling. Weekly i.v. RNAi gene therapy caused reduced tumor expression of immunoreactive EGFR and an 88% increase in survival time of mice with advanced intracranial brain cancer. Conclusions: Weekly i.v. nonviral RNAi gene therapy directed against the human EGFR is a new therapeutic approach to silencing oncogenic genes in solid cancers. This is enabled with a nonviral gene transfer technology that delivers liposome-encapsulated plasmid DNA across cellular barriers with receptor-specific targeting ligands.
Victims of Criminal Homicide in Sweden: A Matched Case-Control Study of Health and Social Risk Factors Among All 1,739 Cases During 1978-1994
Authors: C Allgulander, B Nilsson
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: The psychiatric and medical characteristics of victims of homicide have not been systematically studied and are often confounded by race. This study was undertaken to determine health and social factors contributing to the risk of being murdered in the Swedish, predominantly Caucasian population. METHOD: All 1,739 homicides between 1978 and 1994 in Sweden were studied in terms of variables in national case registers regarding health, crimes, immigration, and marital status. The same data were extracted for matched comparison persons in the general population, with controls for time of exposure. The data were analyzed by conditional logistic regression on matched pairs. RESULTS: Traumatic brain injury, physical abuse, alcohol dependence, and criminal recidivism conferred risk of being murdered. CONCLUSIONS: To the authors' knowledge, this is the first report of traumatic brain injury, in both men and women, as a risk factor for being murdered. Brain injury may mark risk-taking behavior in general or may cause provocative behavior.
The Medical Testimony in the Stockport Case of Poisoning
Authors: J. Rayner
Journal: BMJ (1840)

STOCKPORT CASE OF POISONING.155 it becomes the duty of the Council of the Provincial Asso- ciation to ponder well the probable effects of such a bill on the medical profession in the provinces.'rlhe bill Is initended to contain the constitutional prin- ciple of representation : and, true to its political prototype,
Altered Insula Response to Sweet Taste Processing After Recovery From Anorexia and Bulimia Nervosa
Authors: Tyson A. Oberndorfer, Guido K.W. Frank, Alan N. Simmons, Angela Wagner, Danyale McCurdy, Julie L. Fudge, Tony T. Yang, Martin P. Paulus, Walter H. Kaye
Journal: American Journal of Psychiatry (2013)

Recent studies suggest that altered function of higher-order appetitive neural circuitry may contribute to restricted eating in anorexia nervosa and overeating in bulimia nervosa. This study used sweet tastes to interrogate gustatory neurocircuitry involving the anterior insula and related regions that modulate sensory-interoceptive-reward signals in response to palatable foods.Participants who had recovered from anorexia nervosa and bulimia nervosa were studied to avoid confounding effects of altered nutritional state. Functional MRI measured brain response to repeated tastes of sucrose and sucralose to disentangle neural processing of caloric and noncaloric sweet tastes. Whole-brain functional analysis was constrained to anatomical regions of interest.Relative to matched comparison women (N=14), women recovered from anorexia nervosa (N=14) had significantly diminished and women recovered from bulimia nervosa (N=14) had significantly elevated hemodynamic response to tastes of sucrose in the right anterior insula. Anterior insula response to sucrose compared with sucralose was exaggerated in the recovered group (lower in women recovered from anorexia nervosa and higher in women recovered from bulimia nervosa).The anterior insula integrates sensory reward aspects of taste in the service of nutritional homeostasis. One possibility is that restricted eating and weight loss occur in anorexia nervosa because of a failure to accurately recognize hunger signals, whereas overeating in bulimia nervosa could represent an exaggerated perception of hunger signals. This response may reflect the altered calibration of signals related to sweet taste and the caloric content of food and may offer a pathway to novel and more effective treatments.