tbuckley/cabot-search huggingface dataset:
Immunocytochemical Identification of VPAC1, VPAC2, and PAC1 Receptors in Normal and Neoplastic Human Tissues with Subtype-Specific Antibodies
Authors: Solveig Schulz, Christoph Röcken, Christian Mawrin, Wolfgang Weise, Volker Höllt, Stefan Schulz
Journal: Clinical Cancer Research (2004)

Abstract Human tumors frequently overexpress receptors for vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP). However, none of the VIP/PACAP receptor proteins has been visualized individually in human tumors. Here, we developed and characterized a panel of antipeptide antibodies to the carboxyl-terminal regions of the VIP/PACAP receptor subtypes vasoactive intestinal peptide receptor (VPAC)1, VPAC2, and pituitary adenylate cyclase-activating peptide receptor (PAC)1. Specificity of the antisera was shown by the following: (1) detection of broad bands migrating at Mr 50,000 to 70,000 in Western blots of membranes from receptor-expressing tumors and receptor-transfected cells; (2) cell surface staining of VIP/PACAP receptor-transfected cells; (3) translocation of VIP/PACAP receptor immunostaining in transfected cells after agonist exposure; and (4) abolition of tissue immunostaining by preadsorbtion of the antibodies with their immunizing peptides. The distribution of VIP/PACAP receptors was investigated in 98 human tumors and their tissues of origin. VPAC1, VPAC2, and PAC1 receptors were clearly located at the plasma membrane of the tumor cells in a variety of human neoplasms. In the gastrointestinal tract, VPAC1 receptor immunoreactivity was abundant in the mucosa and myenteric neurons; VPAC2 receptor immunoreactivity was detected in neuroendocrine cells, blood vessels, and smooth muscle; and PAC1 receptor immunoreactivity was found in myenteric neurons. This is the first localization of all of the VIP/PACAP receptor subtypes in human formalin-fixed, paraffin-embedded tissues. VIP/PACAP receptor visualization with this simple and rapid immunohistochemical method will facilitate identification of tumors with a sufficient receptor overexpression for diagnostic or therapeutic intervention.
Regional alteration in cardiac adrenergic function in infarcted and non-infarcted myocardium: Noninvasive assessment using I-123 metaiodobenzylguanidine
Authors: A.Iain McGhie, James R. Corbett, Marvin S. Akers, Padamakar Kulkurni, James T. Willerson
Journal: Journal of the American College of Cardiology (1990)
Granulomatous mycosis fungoides with small intestinal involvement and a fatal outcome
Authors: None Chen, None Tanaka, None Miyakawa
Journal: British Journal of Dermatology (1998)

We report a case of granulomatous mycosis fungoides that progressed into fatal gastrointestinal involvement 4 years after the onset of skin lesions, despite improvement of the skin lesions in response to a combination of PUVA and systemic interferon-gamma therapy. Histological examination showed Pautrier's microabscesses with granuloma annulare-like features and sarcoidal granuloma formation in the plaque stage, proliferation of blast-transformed atypical lymphocytes with persistent granuloma formation in the tumour stage, and metastatic lesions. A literature review of granulomatous mycosis fungoides revealed that 11 of the 24 reported cases died of the disease, and like our case, seven died within 5 years. We suggest that mycosis fungoides with granulomatous reactions does not indicate a favourable prognosis.
ABC of eyes. Injuries to the eye.
Authors: A. R. Elkington, P. T. Khaw
Journal: BMJ (1988)

An injury to the eye or its surrounding tissues is the commonest reason for attendance at the eye casualty department.The history of how the injury was sustained is crucial as it gives clues to what should be looked for during the examination.If there is a story of any high velocity injury (particularly a hammer and chisel injury) a penetrating injury must be strongly suspected, and excluded.If there has been a forceful blunt injury (such as a punch) signs ofa "blow out" fracture should be sought.The circumstances of the injury must be elicited and carefully recorded as these may have important medicolegal implications. Comeal abrasionsCorneal abrasion stained with fluorescein and illuminated with white light.Corneal abrasion stained with fluores4 and illuminated with blue light. Foreign bodiesLower lid gently pulled down to show a conjunctival foreign body.The cornea has also been perforated.Corneal abrasions are the commonest consquence of blunt injury.They may follow injuries with foreign bodies, fingemails, or twigs.Abrasions will be missed if fluorescein is not instilled.The aims of treatment are: * To speed healing and protect the eye-pad the eye.* To prevent infection -apply chloramphenicol ointment.* To relieve pain -instil a cycloplegic (homatropine 2%); give oral', analgesia if necessary.* Use local anaesthetic * Ifit is loose, irrigate * Ifit is adherent, use a cotton wool bud or a piece ofcardboard.
Medicine as a Social Instrument: Medical Education in the Twentieth Century
Authors: C. Sidney Burwell
Journal: New England Journal of Medicine (1951)

MEDICAL education has altered extensively in the fifty years from 1900 to 1950. This is partly because of the rapidity and extent of change in medicine itself and in general science, partly because of changes in the social and economic background of medicine and partly because of changes in the general field of education.It is necessary to impose certain limitations on a discussion of this length; what is written here will be restricted to the history of medical education in this country during the period under discussion. Except for incidental reference, it will be necessary to ignore the great . . .
Business, Trades, and Professions
Authors: Robert D. Gillette
Journal: JAMA (1985)

To the Editor.—  One must admire Dr King's 1 recent endeavor to sort out the semantic issues implicit in the title, Medicine—Trade or Profession? One dictionary 2 lists nine definitions for the word  and even this doesn't do justice to all the nuances of meaning that have arisen from using the term in multiple disparate contexts. For example, the role of  physician is quite different from that of  professional dry cleaner.  Asking whether medicine is a trade or  profession seems most often to be addressing the issue of personal motivation. One is assumed to engage in  trade primarily out of self-interest (making money). The rule of caveat emptor applies, and the tradesperson is considered to have no affirmative responsibility for the purchaser's well-being. The professional, by contrast, is assumed to be trust-worthy and controlled by an ethical system that focuses on the interests of others.
A PRELIMINARY REPORT OF A STUDY OF THE COAGULABILITY OF INFLUENZAL BLOOD
Authors: A. W. Erskine
Journal: JAMA (1918)

<h3>To the Editor:</h3> —During the recent influenza epidemic, one of the most striking symptoms was an almost constant occurrence of hemorrhage. Nosebleed was present nearly always in children, and often in adults. Some of the women had menorrhagia and metrorrhagia, and abortion was frequent. We observed one case with hemorrhage from the bladder and two with hemorrhage from the bowels. The cerebrospinal fluid contained blood in two cases in which lumbar puncture was performed for a suspected meningitis. Bleeding from the gums was common, and several young patients developed hemorrhagic purpura. A majority of the so-called pneumonia patients coughed up bright red blood, some of them dying suddenly from asphyxiation due to active hemorrhage. Sudden death came to one convalescent patient from what was, clinically at least, a hemorrhage in the brain. The regularity with which these various hemorrhages appeared suggested the possibility of there being a change in the
Global climate change: the potential effects on health
Authors: A. J McMichael, A. Haines
Journal: BMJ (1997)

<h3>Objectives</h3> To provide information on the effect of the coronavirus disease of 2019 (COVID-19) pandemic on people with epilepsy and provide consensus recommendations on how to provide the best possible care for people with epilepsy while avoiding visits to urgent care facilities and hospitalizations during the novel coronavirus pandemic. <h3>Methods</h3> The authors developed consensus statements in 2 sections. The first was “How should we/clinicians modify our clinical care pathway for people with epilepsy during the COVID-19 pandemic?” The second was “What general advice should we give to people with epilepsy during this crisis? The authors individually scored statements on a scale of −10 (strongly disagree) to +10 (strongly agree). Five of 11 recommendations for physicians and 3/5 recommendations for individuals/families were rated by all the authors as 7 or above (strongly agree) on the first round of rating. Subsequently, a teleconference was held where statements for which there was a lack of strong consensus were revised. <h3>Results</h3> After revision, all consensus recommendations received a score of 7 or above. The recommendations focus on administration of as much care as possible at home to keep people with epilepsy out of health care facilities, where they are likely to encounter COVID-19 (including strategies for rescue therapy), as well as minimization of risk of seizure exacerbation through adherence, and through ensuring a regular supply of medication. We also provide helpful links to additional helpful information for people with epilepsy and health providers. <h3>Conclusion</h3> These recommendations may help health care professionals provide optimal care to people with epilepsy during the coronavirus pandemic.
Highly active antiretroviral therapy-induced regression of basal cell carcinomas in a patient with acquired immunodeficiency and Gorlin syndrome
Authors: S.Y. Chan, V. Madan, J.T. Lear, M. Helbert
Journal: British Journal of Dermatology (2006)

Journal Article Highly active antiretroviral therapy‐induced regression of basal cell carcinomas in a patient with acquired immunodeficiency and Gorlin syndrome Get access S.Y. Chan, S.Y. Chan The Dermatology Centre, Hope Hospital, Salford M6 8HD, U.K. *Central Manchester Dermatology Centre and †Department of Immunology, Manchester Royal Infirmary, Manchester M13 9WL, U.K Search for other works by this author on: Oxford Academic Google Scholar V. Madan, V. Madan The Dermatology Centre, Hope Hospital, Salford M6 8HD, U.K. *Central Manchester Dermatology Centre and †Department of Immunology, Manchester Royal Infirmary, Manchester M13 9WL, U.K V. Madan E‐mail: vishalmadan@doctors.net.uk Search for other works by this author on: Oxford Academic Google Scholar J.T. Lear, J.T. Lear The Dermatology Centre, Hope Hospital, Salford M6 8HD, U.K. *Central Manchester Dermatology Centre and †Department of Immunology, Manchester Royal Infirmary, Manchester M13 9WL, U.K Search for other works by this author on: Oxford Academic Google Scholar M. Helbert M. Helbert The Dermatology Centre, Hope Hospital, Salford M6 8HD, U.K. *Central Manchester Dermatology Centre and †Department of Immunology, Manchester Royal Infirmary, Manchester M13 9WL, U.K Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 155, Issue 5, 1 November 2006, Pages 1079–1080, https://doi.org/10.1111/j.1365-2133.2006.07479.x Published: 01 November 2006
Abstract 992: PR55alpha, a regulatory subunit of PP2A, specifically regulates PP2A-mediated beta-catenin dephosphorylation
Authors: Wen Zhang, Xi Chen, Tianxin Yu, jianhang jia, Chunming Liu
Journal: Cancer Research (2010)

Abstract BACKGROUND: Wnt/beta-catenin signaling plays essential roles in development and tumorigenesis. A central question in Wnt signaling is the regulation of beta-catenin phosphorylation and degradation. Our previous work found that beta-catenin is sequentially phosphorylated by CKIalpha and GSK3, which creates binding site for beta-Trcp, leading to degradation via the ubiquitination/proteasome machinery. Mutations in beta-catenin or APC genes that prevent beta-catenin phosphorylation or ubiquitination/degradation lead ultimately to cancer. In addition to the involvement of kinases, protein phosphatases, such as PP1, PP2A and PP2C, are also implicated in Wnt/beta-catenin regulation. However, which phosphatase dephosphorylates beta-catenin in vivo and how the specificity of beta-catenin dephosphorylation is regulated are not clear. In this study, we show that PP2A regulates beta-catenin phosphorylation and degradation in vivo. PP2A consists of a catalytic subunit (PP2Ac), a structure subunit (PR65/A) and variable regulatory B subunit (PR/B, PR/B’, PR/B”, or PR/B’’’). The substrate specificity of PP2A is thought to be determined by its B subunit. We further identified that PR55alpha is the regulatory B subunit that controls PP2A-mediated beta-catenin dephosphorylation. RESULTS: Toward the goal of understanding the mechanism of beta-catenin phosphorylation, we carried out siRNA screening targeting several major phosphatases, in which we found that PP2A dephosphorylates beta-catenin. We demonstrate that PP2A is required for Wnt/beta-catenin signaling in Drosophila. Moreover, by siRNA screening, we have identified PR55alpha as the regulatory subunit of PP2A that controls beta-catenin phosphorylation and degradation. Mechanistically, we found that PR55alpha directly interacts with beta-catenin and regulates PP2A-mediated beta-catenin dephosphorylation in Wnt signaling. PR55alpha but not the catalytic subunit, PP2Ac, directly interacts with beta-catenin. RNAi knockdown of PR55alpha elevates beta-catenin phosphorylation and decreases Wnt signaling, whereas overexpressing PR55alpha enhances Wnt signaling. Taken together, our results suggest that PR55alpha specifically regulates PP2A-mediated beta-catenin dephosphorylation and plays an essential role in Wnt signaling. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 992.
Interaction between paracrine tumor necrosis factor-alpha and paracrine angiotensin II during myocardial ischemia
Authors: Inna Frolkis, Jacob Gurevitch, Yael Yuhas, Adrian Iaina, Yoram Wollman, Tamara Chernichovski, Yosef Paz, Menachem Matsa, Dimitri Pevni, Amir Kramer, Itzhak Shapira, Rephael Mohr
Journal: Journal of the American College of Cardiology (2001)
Disruption of cell-cell adhesion in an inbred strain of hereditary cardiomyopathic hamster (Bio 14.6)
Authors: Y. Fujio, F. Yamada-Honda, N. Sato, H. Funai, A. Wada, N. Awata, N. Shibata
Journal: Cardiovascular Research (1995)

Disarrangement of cardiomyocytes is a pathological characteristic of dilated cardiomyopathy. Hereditary cardiomyopathic hamster Bio 14.6, a model of dilated cardiomyopathy, displays disorder of cardiomyocyte arrangement. The aim of this study was to analyse the disturbance of cell alignment from the point of view of the cell-cell adhesion system in Bio 14.6.Cardiomyopathic hamster Bio 14.6 was used as a model of dilated cardiomyopathy. Histological study was performed by light and electron microscopy. Disorder of the adherens junction-specific cell-adhesion molecule (A-CAM) was analysed by immunofluorescent microscopy and immunoblotting with anti-A-CAM antibody.Hematoxylin-eosin staining revealed that intercalated disks were identifiable less clearly in cardiomyopathy than in a normal cardiac muscle. It was disclosed by electron microscopy that cardiomyocytes adhered to each other with reduction in subsarcolemmal electron density at intercalated disks in Bio 14.6 compared with normal hamsters. We examined the localization of the A-CAM molecule in heart by immunofluorescent microscopy. In contrast to normal cardiac samples, fluorescence was weak in intensity and unclearly demarcated in the Bio 14.6 hamsters. We measured the content of A-CAM in the heart. In Bio 14.6 hamsters, the content of A-CAM was 60 +/- 11% of that measured in normal adult hamsters. A-CAM was reduced to a lesser extent (81 +/- 12%) in the newborn hamsters.In Bio 14.6 hamster, structural disturbance of the intercalated disks was found on histological examination of the heart. Biochemically, A-CAM, which plays a role in intercellular adhesion in intercalated disk areas, decreased significantly. These results suggest that cardiomyopathy may be accompanied by structural disruption of cell-cell adhesion in intercalated disk regions, which may lead to the pathological feature of disarranged cardiomyocytes.
Computed Tomography — A Controversy Revisited
Authors: Ronald G. Evens
Journal: New England Journal of Medicine (1984)

The year 1983 marked the 10th anniversary of the introduction of computed tomography (CT) in the United Slates. In 1978 this diagnostic technique was still the focus of intense controversy,1 , 2 primarily because of its cost. Considered by physicians to be revolutionary and a major advance, it was widely regarded as an example of "technology running wild" by those who focused on the increasing cost of medical care, including health planners, regulatory agencies, and politicians. The critical issues were the technical aspects, the clinical use and efficacy, the costs and their control (specifically through national and regional health planning), and the . . .
Physiological Pharmacology; a Comprehensive Treatise. Vol I: The Nervous System. Part A: Central Nervous System Drugs.
Authors: E. W. Maynert
Journal: JAMA (1963)

In the foreword to this treatise the editors state that their aim is "to record and interpret all of the significant findings, regardless of age, and thereby portray the framework of experimental evidence upon which pharmacodynamics is built." Their start toward this ambitious goal is 12 disparate chapters on the central nervous system. Adriani's treatment of the absorption and elimination of anesthetics suffers from his complete neglect of mathematics and his failure to present the simple laws governing the solubility of gases, the foundation of his subject. The electrophysiological discussions by Ngai, Brazier, and others seem unusually eclectic; they might have been improved somewhat if reference were made to other chapters. Bush's presentation of the principles involved in the absorption and distribution of drugs is satisfactory, but the section on metabolic fate is neither detailed enough or general enough to be useful. It is disappointing that in his chapter on
Amino acid substitutions in the hormone-binding domain of the human androgen receptor alter the stability of the hormone receptor complex.
Authors: M Marcelli, S Zoppi, C M Wilson, J E Griffin, M J McPhaul
Journal: Journal of Clinical Investigation (1994)

We have investigated the basis of androgen resistance in seven unrelated individuals with complete testicular feminization or Reifenstein syndrome caused by single amino acid substitutions in the hormone-binding domain of the androgen receptor. Monolayer-binding assays of cultured genital skin fibroblasts demonstrated absent ligand binding, qualitative abnormalities of androgen binding, or a decreased amount of qualitatively normal receptor. The consequences of these mutations were examined by introducing the mutations by site-directed mutagenesis into the androgen receptor cDNA sequence and expressing the mutant cDNAs in mammalian cells. The effects of the amino acid substitutions on the binding of different androgens and on the capacity of the ligand-bound receptors to activate a reporter gene were investigated. Substantial differences were found in the responses of the mutant androgen receptors to incubation with testosterone, 5 alpha-dihydrotestosterone, and mibolerone. In several instances, increased doses of hormone or increased frequency of hormone addition to the incubation medium resulted in normal or near normal activation of a reporter gene by cells expressing the mutant androgen receptors. These studies suggest that the stability of the hormone receptor complex is a major determinant of receptor function in vivo.
III. Meta-Analysis of Risedronate for the Treatment of Postmenopausal Osteoporosis
Authors: Ann Cranney, Peter Tugwell, Jonathan Adachi, Bruce Weaver, Nicole Zytaruk, Alexandra Papaioannou, Vivian Robinson, Beverley Shea, George Wells, Gordon Guyatt
Journal: Endocrine Reviews (2002)

Objective: To review the effect of risedronate on bone density and fractures in postmenopausal women.Data Sources: We searched MEDLINE from 1966 to the end of 2000 and examined citations of relevant articles and the proceedings of international osteoporosis meetings.Study Selection: We included eight randomized, placebocontrolled trials of postmenopausal women receiving risedronate or placebo with a follow-up of at least one year and providing data on bone density or fracture rate.Data Extraction: For each trial, two independent reviewers assessed the methodological quality and abstracted data.Data Synthesis: The major methodological limitation of the trials was the loss to follow-up, which was over 20% in most trials and over 35% in the largest study.However, the magnitude of the treatment effect was unrelated to loss to follow-up, and in one of the largest trials, more high-risk patients were lost to follow-up in the control than in the treatment group.The pooled relative risk (RR) for vertebral fractures in women given 2.5 mg or more of risedronate was 0.64 [95% confidence interval (CI) 0.54, 0.77].The pooled RR of nonvertebral fractures in patients given 2.5 mg or more of risedronate was 0.73 (95% CI 0.61, 0.87).Risedronate produced positive effects on the percentage change in bone density of the lumbar spine, combined forearm, and femoral neck that were generally larger with the 5-mg daily dose than with cyclical administration or the 2.5-mg dose.The pooled estimate of the difference in percentage change between 5 mg risedronate and placebo after the final year of treatment (1.5-3 yr) was 4.54% (95% CI 4.12, 4.97) for the lumbar spine, and 2.75% (95% CI 2.32, 3.17) at the femoral neck.Conclusions: Risedronate substantially reduces the risk of both vertebral and nonvertebral fractures.This fracture reduction is accompanied by an increase in bone density of the lumbar spine and femoral neck in both early postmenopausal women and those with established osteoporosis. B.
Cisplatin impairs fluid and electrolyte absorption in rat small intestine: a role for 5-hydroxytryptamine
Authors: C P Bearcroft, P Domizio, F H Mourad, E A André, M J G Farthing
Journal: Gut (1999)

Background The antineoplastic drug cisplatin has been widely used for the treatment of cancer in humans but its use has been limited by vomiting and diarrhoea. Cisplatin releases 5-hydroxytryptamine into the gut which is thought to be the major mediator of cisplatin induced vomiting. Aim To determine whether cisplatin affects fluid and electrolyte transport in rat jejunum and whether this change can be modulated by the 5-hydroxytryptamine 3 receptor antagonist, ondansetron. Methods Jejunal perfusion in rats in vivo was performed one hour after intraperitoneal cisplatin (5 and 10 mg/kg) administration. The effect of pretreatment with subcutaneous ondansetron 300 μg/kg was investigated. Results Median net fluid absorption after cisplatin 10 mg/kg (67 μl/min/g dry intestinal weight (interquartile range 46 to 100); n = 15) was reduced compared with controls (120 (107 to 151) μl/min/g; n = 13; p&lt;0.001). Ondansetron reversed the impairment of jejunal fluid absorption produced by cisplatin to normal (161 (130 to 176) μl/min/g; n = 11; p&lt;0.001). Electrolyte movement paralleled fluid movement. Jejunal histological examination of sections from cisplatin treated animals showed villus damage, which was not prevented by pretreatment with ondansetron. Conclusion These findings suggest that diarrhoea during cisplatin therapy may be due to altered fluid transport in the small bowel. The reversal of fluid transport to normal in the presence of a 5-hydroxytryptamine 3 receptor antagonist suggests that 5-hydroxytryptamine is a local mediator in the small intestine.