tbuckley/cabot-search huggingface dataset:
Discovery of common human genetic variants of GTP cyclohydrolase 1 (GCH1) governing nitric oxide, autonomic activity, and cardiovascular risk
Authors: Lian Zhang, Fangwen Rao, Kuixing Zhang, Srikrishna Khandrika, Madhusudan Das, Sucheta M. Vaingankar, Xuping Bao, Brinda K. Rana, Douglas W. Smith, Jennifer Wessel, Rany M. Salem, Juan L. Rodriguez-Flores, Sushil K. Mahata, Nicholas J. Schork, Michael G. Ziegler, Daniel T. O’Connor
Journal: Journal of Clinical Investigation (2007)

GTP cyclohydrolase 1 (GCH1) is rate limiting in the provision of the cofactor tetrahydrobiopterin for biosynthesis of catecholamines and NO. We asked whether common genetic variation at GCH1 alters transmitter synthesis and predisposes to disease. Here we undertook a systematic search for polymorphisms in GCH1, then tested variants' contributions to NO and catecholamine release as well as autonomic function in twin pairs. Renal NO and neopterin excretions were significantly heritable, as were baroreceptor coupling (heart rate response to BP fluctuation) and pulse interval (1/heart rate). Common GCH1 variant C+243T in the 3'-untranslated region (3'-UTRs) predicted NO excretion, as well as autonomic traits: baroreceptor coupling, maximum pulse interval, and pulse interval variability, though not catecholamine secretion. In individuals with the most extreme BP values in the population, C+243T affected both diastolic and systolic BP, principally in females. In functional studies, C+243T decreased reporter expression in transfected 3'-UTRs plasmids. We conclude that human NO secretion traits are heritable, displaying joint genetic determination with autonomic activity by functional polymorphism at GCH1. Our results document novel pathophysiological links between a key biosynthetic locus and NO metabolism and suggest new strategies for approaching the mechanism, diagnosis, and treatment of risk predictors for cardiovascular diseases such as hypertension.
The psychiatric oligarchs who medicalise normality
Authors: Des Spence
Journal: BMJ (2012)

Mental health should be a priority for all societies and its stigma always challenged. However, the US Centers for Disease Control and Prevention (CDC) reports that a staggering 25% of people in the United States have a “mental illness.”1 This is so large a figure that there can be only one conclusion: psychiatry is medicalising normality. The definition of a “mental illness” is one of opinion. These opinions are drawn from a small group of psychiatric oligarchs who author the Diagnostic and Statistical Manual of Mental Disorders (DSM). Their opinions are polluted, however: …
Emergency Medical Services, 1979
Authors: Edward P. Hoffer
Journal: New England Journal of Medicine (1979)

Improved patient care can result from changes in the organization and delivery of care as well as from new drugs and surgical techniques. Witness, for example, the dramatic changes that have occurred in the delivery of emergency medical services over the past five years.HistoryIn 1966, the National Academy of Sciences published its landmark study, "Accidental Death and Disability: The neglected disease of modern society."1 The study labeled this "neglected epidemic" the leading cause of death in children and young adults and the nation's most important environmental health problem. Although the academy focused attention on failures in the civilian . . .
Murine mast cells synthesize basement membrane components. A potential role in early fibrosis.
Authors: H L Thompson, P D Burbelo, G Gabriel, Y Yamada, D D Metcalfe
Journal: Journal of Clinical Investigation (1991)

Mast cells are resident in tissues, particularly in association with endothelial and epithelial cell basement membranes, and increase at sites of inflammation, injury, and fibrosis. Although mast cells are known to both release and generate proinflammatory molecules in response to inflammatory stimuli, little is known about their normal biologic function. Here we demonstrate that IL-3-dependent mouse PT18 mast cells, mouse bone marrow-derived mast cells, and rat basophilic leukemia cells express large amounts of mRNA for collagen IV, laminin, and heparan sulfate proteoglycan. Western blot analysis confirmed that mast cells synthesize and secrete significant amounts collagen IV and laminin B1 and B2 chains. These data suggest that mast cells may contribute to normal tissue repair and/or the early overproduction of basement membrane components seen in a variety of fibrotic conditions.
Examining the Cost-effectiveness of 2-Level Cervical Total Disc Replacement
Authors: Shawn L. Hervey-Jumper, Paul Park
Journal: JAMA Surgery (2014)

Cervical total disc replacementwasdeveloped to treat symptomsassociatedwithdiscdegenerationwhilepreservingphysiological motion. Several clinical trials have compared its use with traditional anterior cervical discectomy and fusion for both single-level and multilevel disease.1,2 Ament et al3 analyzed data from a published multicenter randomizedclinical trial by Davis et al4 that demonstrated the clinical superiority of the Mobi-C cervical artificial disc vs anterior discectomy and fusion for 2-level contiguous degenerative disc disease and proposed that 2-level total cervical disc replacement is a cost-effective intervention. This is a potentially significant conclusion. As health care costs continue to increase, there is growing scrutiny ofmedical and surgical treatments offered topatients that, despite efficacy,maybecostprohibitive.Using thequality-adjusted lifeyear scale, the authors showed that 2-level cervical total disc replacement is a cost-effective treatment modality.3 However, several limitationsneed tobeconsidered.First, datawere derived from a multicenter randomized clinical study with strict inclusionandexclusion criteria.As such, the resultsmay not be generalizable to the general populationof patientswho are candidates for anterior cervical surgery. In addition, although thedecisionanalyticmodelingused in thestudyseems reasonable, assumptions that may not be valid were used for the analysis. Even so, the results of this study provide compelling evidence that cervical total disc replacement is a costeffective option for 2-level symptomatic cervical spondylitic disease.
Water and Electrolyte Metabolism in Congestive Heart Failure
Authors: GEORGE E. MILLER
Journal: Circulation (1951)

The over-all metabolic balance of sodium, chloride and water has been studied in 8 subjects recovering from congestive heart failure. During the release of edema the observed loss of water in excess of sodium and chloride, as they are normally present in extracellular fluid, has suggested that the concept of initial retention of sodium in the development of heart failure may be untenable.
The relationship between tumour necrosis factor (TNF)-α promoter and<i>IL12B</i>/<i>IL-23R</i>genes polymorphisms and the efficacy of anti-TNF-α therapy in psoriasis: a case-control study
Authors: E. Gallo, T. Cabaleiro, M. Román, G. Solano-López, F. Abad-Santos, A. García-Díez, E. Daudén
Journal: British Journal of Dermatology (2013)

Journal Article The relationship between tumour necrosis factor (TNF)‐α promoter and IL12B/IL‐23R genes polymorphisms and the efficacy of anti‐TNF‐α therapy in psoriasis: a case–control study Get access E. Gallo, E. Gallo Department of Dermatology Hospital Universitario de la Princesa Instituto de Investigación Sanitaria Princesa (IP) C/Diego de León 62 28006 Madrid Spain Correspondence Elena Gallo. E‐mail: egallo@aedv.es Search for other works by this author on: Oxford Academic Google Scholar T. Cabaleiro, T. Cabaleiro Department of Clinical Pharmacology Hospital Universitario de la Princesa Instituto Teófilo Hernando Instituto de Investigación Sanitaria Princesa (IP) Madrid Spain Search for other works by this author on: Oxford Academic Google Scholar M. Román, M. Román Department of Clinical Pharmacology Hospital Universitario de la Princesa Instituto Teófilo Hernando Instituto de Investigación Sanitaria Princesa (IP) Madrid Spain Search for other works by this author on: Oxford Academic Google Scholar G. Solano‐López, G. Solano‐López Department of Dermatology Hospital Universitario de la Princesa Instituto de Investigación Sanitaria Princesa (IP) C/Diego de León 62 28006 Madrid Spain Search for other works by this author on: Oxford Academic Google Scholar F. Abad‐Santos, F. Abad‐Santos Department of Clinical Pharmacology Hospital Universitario de la Princesa Instituto Teófilo Hernando Instituto de Investigación Sanitaria Princesa (IP) Madrid SpainCentro de Investigación Biomédica en Red de enfermedades hepáticas y digestivas (CIBERehd) ISCIII Madrid Spain Search for other works by this author on: Oxford Academic Google Scholar A. García‐Díez, A. García‐Díez Department of Dermatology Hospital Universitario de la Princesa Instituto de Investigación Sanitaria Princesa (IP) C/Diego de León 62 28006 Madrid Spain Search for other works by this author on: Oxford Academic Google Scholar E. Daudén E. Daudén Department of Dermatology Hospital Universitario de la Princesa Instituto de Investigación Sanitaria Princesa (IP) C/Diego de León 62 28006 Madrid Spain Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 169, Issue 4, 1 October 2013, Pages 819–829, https://doi.org/10.1111/bjd.12425 Published: 01 October 2013
Increasing use of coronary stents is associated with a reduced requirement for repeat intervention in a large unselected population of patients referred for PTCA
Authors: J.M. Rankin, R.A. Milner, R.G. Carere, D.J. Hilton, M.A. Henderson, R.I. Hayden, C.E. Buller
Journal: Journal of the American College of Cardiology (1998)
Psychiatric Administration: A Comprehensive Text for the Clinician-Executive
Authors: Elissa P. Benedek
Journal: JAMA (1983)

Drs Talbott and Kaplan introduce this 410-page edited volume by informing the reader that this text is a combination of their long years of practical experience and an attempt to give structure and new meaning to their experience. They remind readers that since World War II, psychiatrist-clinicians have become "executive policy makers in large organizations, which are subject to unpredictable, and often uncontrollable, internal and external forces." Drs Talbott and Kaplan note that they, along with their peer group, had little or no formal training in administration. Their training has been on the job or, rather, in the "battle field." In my experience, the fortunate psychiatric administrator has had a mentor or preceptor who served as a role model. Psychiatric administration has been passed from teacher to student via the oral tradition. The value of this volume is that it converts the best of the oral tradition to brief, well-written
ABC of one to seven. Febrile convulsions.
Authors: H B Valman
Journal: BMJ (1993)

DefinitionA febrile convulsion is a fit occurring in a child aged from 6 months to 5 years, precipitated by fever arising from infection outside the nervous system in a child who is otherwise neurologically normal.Convulsions with fever include any convulsion in a child of any age with fever of any cause.Among children who have convulsions with fever are those with pyogenic or viral meningitis, encephalitis, or cerebral palsy with intercurrent infections.Children who have a prolonged fit or who have not completely recovered within one hour should be suspected of having one of these conditions.Most of the fits that occur between the ages of 6 months and 5 years are simple febrile convulsions and have an excellent prognosis.If there is no fever the possibility of epilepsy should be considered.Often fever is recognised only when a convulsion has already occurred.An abrupt rise in temperature rather than a high level is important.There may be a frightened cry followed by abrupt loss of consciousness with muscular rigidity, which form the tonic stage.Cessation of respiratory movements and incontinence ofurine and faeces may occur during this stage, which usually lasts up to half a minute.The clonic stage which follows consists of repetitive movements of the limbs or face.By arbitrary definition, in simple febrile convulsions the fit lasts less than 20 minutes, there are no focal features, and the child is aged between 6 months and 5 years and has been developing normally.Rigors may occur in any acute febrile illness, but there is no loss of consciousness. Emergency treatmentNursing position to avoid vomiting with aspiration.* Last <20minutes * No focal features * Occur in children aged 6 months to 5 years * Occur in children with no development or neurological abnormalities * Not repeated in the same episode * Complete recovery within 1 hour Rectal diazepam is the anticonvulsant of choice
Pemphigus Antibodies Identify a Cell Surface Glycoprotein Synthesized by Human and Mouse Keratinocytes
Authors: John R. Stanley, Mina Yaar, Pamela Hawley-Nelson, Stephen I. Katz
Journal: Journal of Clinical Investigation (1982)

Pemphigus is an antibody-mediated autoimmune skin disease in which loss of cell-to-cell contacts in the epidermis results in blister formation. Patients with pemphigus develop antibodies that bind to the keratinocyte cell surface, the site of primary pathology. The purpose of this study was to characterize the antigen(s) to which pemphigus antibodies bind. Because we could detect pemphigus antigen by indirect immunofluorescence on the surface of multiply-passaged cells in cultures of both a spontaneously transformed mouse keratinocyte cell line (Pam) and normal human epidermal cells, we used these cells as a source of antigen. In order to demonstrate biosynthesis of antigen and to characterize the antigen(s), we radiolabeled cell cultures with [14C]glucosamine or d-[2-3H]mannose and used different pemphigus sera to immunoprecipitate antigen from nonionic detergent extracts of these labeled cells. Specifically precipitated radiolabeled molecules were identified using sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE) and fluorography. Sera from five of seven pemphigus patients specifically precipitated (from extracts of both Pam cells and human epidermal cells) a molecule that, when reduced, was ∼130 kD, whereas seven normal human sera and two pemphigoid sera did not precipitate this molecule. The findings that (a) these precipitated molecules comigrated on SDS-PAGE and that (b) the 130-kD molecule could no longer be precipitated from cell extracts that had been previously reacted with a pemphigus serum, indicate that reactive pemphigus sera bind the same molecule. The molecule was not detected in the culture medium of these cells. This finding, along with the cell surface immunofluorescence pattern, suggests that the antigen is bound to the cell surface. Cultured mouse and human fibroblasts do not synthesize the antigen. The antigen contains protein because it was degraded by V8 protease and chymotrypsin, and it could also be labeled with [14C]amino acids. It is probably not a sulfated proteoglycan because it did not label with 35SO4. Taken together, these data indicate that some, but not all, pemphigus sera bind a specific cell surface glycoprotein that is synthesized by keratinocytes.
Prospective randomised controlled trial of methods of call and recall for cervical cytology screening.
Authors: M. Pierce, S. Lundy, A. Palanisamy, S. Winning, J. King
Journal: BMJ (1989)

To discover whether systematic methods of call and recall are more effective than a non-systematic method and to see which of the two systematic methods was more effective.Prospective randomised controlled trial over a year.One group general practice.416 Women over 35 eligible for a smear test who had never had a cervical smear test or in whom a smear test was overdue (previous test more than five years before).One group received written invitations to have a smear taken. The second group had their notes tagged so that the doctor would remind them (when they attended for another reason) to have a smear test. No special intervention was made in the third group.Performance of a cervical smear test during the year of the study.32% (45/140) of the screened group, 27% (39/142) of the tagged group, and 15% (20/134) of the control group had a smear test during the year. The percentage of women having a smear test in the screened group was not significantly different from that in the tagged group, but the percentages in the two groups were significantly different from that in the control group. Whether a woman had had a previous smear test significantly affected the uptake of the invitation to have a smear test independently of the method of invitation.The systematic methods of call and recall were more effective than a non-systematic method. There was no significant difference between the two systematic methods (sending letters or tagging the notes) at one year.
Nutritional Aspects of Metabolism of Growth and Development
Authors: Calvin Woodruff
Journal: JAMA (1966)

A growth pattern that is normal for the first half year of life with growth failure and partial recovery during the next three or four years is common in many developing countries. Biochemical evidence of anemia, hypoproteinemia, and a varying spectrum of relative vitamin deficiency is also found. Similar patterns for growth and biochemical findings were found in a group of hospitalized infants in the United States. The multiple conditioning factors in the development of these patterns are emphasized.
Abstract 2169: The effect of WT1 on E-cadherin expression in prostate cancer cells
Authors: Adina Brett, Gail Fraizer, Kurtis Eisermann
Journal: Cancer Research (2011)

Abstract Prostate carcinoma is the most common malignancy and second leading cause of death among American men. The molecular mechanisms that control the progression of this type of cancer are still poorly understood. One of the genes expressed in prostate cancer epithelium is the zinc finger transcription factor Wilms’ Tumor 1, WT1. Previous studies in our lab have shown WT1 protein in a majority of high grade prostate tumor sections with little or no WT1 staining in non-neoplastic or benign prostatic hyperplasia (BPH) tissues. However, a mechanistic role for WT1 in prostate cancer has not been established. Recently, WT1 has been associated with the regulation of cell adhesion molecules such as E-cadherin in NIH 3T3 cells and epicardial cells. Loss of E-cadherin expression is frequently associated with increased cellular motility and tumor invasion. Several regulatory mechanisms controlling E-cadherin gene expression have been proposed in breast cancer cells, however the mechanisms of regulation of E-cadherin gene expression in prostate cancer cells are not yet understood. The objective of this study was to determine whether WT1 might regulate E-cadherin expression and contribute to cancer progression in prostate cancer cells. First, potential WT1 binding sites were identified in the promoter of the E-cadherin gene using a bioinformatics approach. Chromatin Immunoprecipitation (ChIP) showed direct in vivo binding of WT1 to the E-cadherin promoter in the chromatin of LNCaP and PC3 cells. The effect of transfection of prostate cancer cells with a GFP/WT1 expression construct was then tested by quantitative real-time PCR (QRT-PCR). QRT-PCR results showed a decrease in E-cadherin transcripts in GFP/WT1 transfected prostate cancer cells. Conversely, knockdown of WT1 mRNA in siWT1 transfected LNCaP cells, showed increased levels of E-cadherin mRNA. Moreover, co-transfection of WT1 expression construct with an E-cadherin promoter reporter construct showed that WT1 decreased the activity of the proximal E-cadherin promoter in PC3 cells. Overall these results demonstrated that WT1 modulated E-cadherin expression in prostate cancer cells and suggests a novel mechanism whereby WT1 may increase migration by decreasing E-cadherin levels, a novel role for WT1 mediated prostate cancer progression. This work was supported by NIHR15CA11360 and Ohio Board of Regents. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2169. doi:10.1158/1538-7445.AM2011-2169
Functional analysis of influenza-specific helper T cell clones in vivo. T cells specific for internal viral proteins provide cognate help for B cell responses to hemagglutinin.
Authors: P A Scherle, W Gerhard
Journal: The Journal of Experimental Medicine (1986)

We compared the effects of adoptively transferred Th cell clones specific for the influenza hemagglutinin (HA), matrix (M), or nucleoprotein (NP) on the antibody response of nude mice infected with A/PR/8/34 influenza virus. We show that the production of antibodies to the HA absolutely requires the presence of virus-specific Th cells. Further, transfer of a Th clone specific for the internal proteins, M or NP, was as effective as was transfer of an HA-specific clone in supporting an antibody response to the HA. With each of the clones, the kinetics of the response were accelerated by approximately 3 d compared with the antibody response of normal BALB/c mice. The HA- and M-specific clones supported an isotype switch from IgM to IgG and IgA similar to that which occurs during a normal antibody response. Finally, as shown by coinfection experiments, the response required a cognate T-B interaction whether the determinants recognized by the Th and B cell are located on the same viral protein or on different viral proteins within the same virus particle. The implications of these findings for understanding the T-B interactions that occur during an effective antiviral antibody response are discussed.
Clinical and Biochemical Differences in Patients Having Parkinson Disease With vs Without<i>GBA</i>Mutations
Authors: Lama M. Chahine, Judy Qiang, Emily Ashbridge, James Minger, Dora Yearout, Stacy Horn, Amy Colcher, Howard I. Hurtig, Virginia M-Y. Lee, Vivianna M. Van Deerlin, James B. Leverenz, Andrew D. Siderowf, John Q. Trojanowski, Cyrus P. Zabetian, Alice Chen-Plotkin
Journal: JAMA Neurology (2013)

Biochemical abnormalities present in GBA (mut/wt) carriers may offer new pathogenetic insights to and potential therapeutic targets in Parkinson disease (PD).To determine whether patients having PD with vs without GBA mutations differ in clinical phenotype or plasma protein expression.Case-control study of patients having PD with vs without GBA mutations. Clinical characteristics were compared between groups, and biochemical profiling of 40 plasma proteins was performed to identify proteins that differed in expression between groups.The discovery cohort included 20 patients having PD with GBA mutations. Clinical characteristics of GBA-associated PD cases were compared with those of 242 patients having PD in whom GBA mutations were excluded by full gene sequencing.Biochemical profiling was available for all 20 GBA-associated PD cases, as well as a subset (87 of 242) of the GBA-negative PD cases. The replication cohort included 19 patients having PD with GBA mutations and 41 patients having PD without GBA mutations.Compared with patients having PD without GBA mutations, patients having PD with GBA mutations were younger at disease onset (P = .04) and were more likely to demonstrate cognitive dysfunction (P = .001). In a multiple regression model that included age, sex, and assay batch as covariates, GBA mutation status was significantly associated with plasma levels of interleukin 8 (P = .001), monocyte chemotactic protein 1 (P = .008), and macrophage inflammatory protein 1α (P = .005). The association between interleukin 8 and GBA mutation status was replicated (P = .03) in a separate cohort of patients having PD with vs without GBA mutations.Patients having PD with GBA mutations have earlier age at disease onset and are more likely to demonstrate cognitive dysfunction. Monocyte-associated inflammatory mediators may be elevated in patients having PD with GBA mutations.