tbuckley/cabot-search huggingface dataset:
On the Biological Role of Cyclic AMP
Authors: Earl W. Sutherland
Journal: JAMA (1970)

Before discussing the role of cyclicadenylate, or adenosine 3′,5′-monophosphate (cyclic AMP) in biology, I would like to make a few brief remarks about another subject, the role of the basic scientist in medicine. I would like to hope that this and the subject that I have been asked to write about are not completely unrelated. I bring this other subject up for two main reasons. First, I am myself optimistic about what the scientist can offer to the world, and especially to medicine. But second, I find others, ranging from beginning medical students to high government officials, who are not so optimistic. I am not overly concerned about our medical students, for the young have always been short on historical perspective and long on idealism. They sense, quite rightly in my view, that American medicine has fallen short of its earlier promise, and they are impatient to do something about
The role of endogenous heme oxygenase in the initiation of liver injury following limb ischemia/reperfusion
Authors: Robert G. Nie, Sarah D. McCarter, Kenneth A. Harris, Patty J. Lee, Xuchen Zhang, Aurelia Bihari, Daryl Gray, Christian Wunder, Robert W. Brock, Richard F. Potter
Journal: Journal of Hepatology (2002)
Immunohistochemical Expression of Ki-67 Antigen, Cox-2 and Bax/Bcl-2 in Prostate Cancer; Prognostic Value in Biopsies and Radical Prostatectomy Specimens
Authors: J RUBIO, D RAMOS, J LOPEZGUERRERO, I IBORRA, A COLLADO, E SOLSONA, S ALMENAR, A LLOMBARTBOSCH
Journal: European Urology (2005)
Conditional Ablation of Nonmuscle Myosin II-B Delineates Heart Defects in Adult Mice
Authors: Xuefei Ma, Kazuyo Takeda, Aman Singh, Zu-Xi Yu, Patricia Zerfas, Anthony Blount, Chengyu Liu, Jeffrey A. Towbin, Michael D. Schneider, Robert S. Adelstein, Qize Wei
Journal: Circulation Research (2009)

Rationale : Germline ablation of the cytoskeletal protein nonmuscle myosin II (NMII)-B results in embryonic lethality, with defects in both the brain and heart. Tissue-specific ablation of NMII-B by a Cre recombinase strategy should prevent embryonic lethality and permit study of the function of NMII-B in adult hearts. Objective : We sought to understand the function of NMII-B in adult mouse hearts and to see whether the brain defects found in germline-ablated mice influence cardiac development. Methods and Results : We used a loxP/Cre recombinase strategy to specifically ablate NMII-B in the brains or hearts of mice. Mice ablated for NMII-B in neural tissues die between postnatal day 12 and 22 without showing cardiac defects. Mice deficient in NMII-B only in cardiac myocytes (B αMHC /B αMHC mice) do not show brain defects. However, B αMHC /B αMHC mice display novel cardiac defects not seen in NMII-B germline-ablated mice. Most of the B αMHC /B αMHC mice are born with enlarged cardiac myocytes, some of which are multinucleated, reflecting a defect in cytokinesis. Between 6 to 10 months, they develop a cardiomyopathy that includes interstitial fibrosis and infiltration of the myocardium and pericardium with inflammatory cells. Four of 5 B αMHC /B αMHC hearts develop marked widening of intercalated discs. Conclusions : By avoiding the embryonic lethality found in germline-ablated mice, we were able to study the function of NMII-B in adult mice and show that absence of NMII-B in cardiac myocytes results in cardiomyopathy in the adult heart. We also define a role for NMII-B in maintaining the integrity of intercalated discs.
Identification of disease genes by expression profiling
Authors: R. Bals, B. Jany
Journal: European Respiratory Journal (2001)

The human genome has been completely sequenced. The development of innovative methodologies and tools to understand the functions of human genes in health and disease will allow the data of the human genome project to be utilized. This paper reviews methods that can be used to detect and isolate genes that are specifically expressed in certain diseases or that are specific to cell types. First, classical methods, such as differential screening of complementary deoxyribonucleic acid libraries and subtractive techniques, are described. Methods based on polymerase chain reaction (PCR), such as differential display PCR or serial analysis of gene expression, will then be discussed. Finally, recent developments in gene chip technology and basic principles of functional genomics will be illustrated. Future developments will link the results of genomic approaches to data obtained by other systematic methods, such as proteomics (<i>i.e.</i> the systematic, large scale analysis of proteins), and will allow the production of a detailed molecular characterization of diseases, disease stages, tissues, or cell types. Methods to detect disease or cell type-specific gene expression patterns will play an important role in the future of basic research, as well as the development of novel diagnostic procedures and identification of therapeutic targets.
Blood Cholinesterase Levels in Organic Phosphate Intoxication
Authors: Mitchell R. Zavon
Journal: JAMA (1965)

The inhibition of cholinesterase (ChE) activity by the organic phosphate insecticides provides a sensitive indicator of absorption of these compounds. In order to interpret the laboratory results of the ChE activity, one must consider several factors, including the accuracy of the determination. Unless the laboratory personnel are accustomed to performing the analysis (Michel method), a duplicate sample should be sent to a laboratory where the test is commonly done for comparison. Blood is collected in a heparinized capillary tube, and the plasma and red blood cells (RBC) are separated as soon as possible. The test may be performed with as little as 0.02 ml of heparinized blood. 1   Since there is a 100% variation in the normal ChE activity among different individuals, and since the same person may show a variation of as much as 25% at different times, it is extremely helpful if the normal values for the individual
INFECTIOUS ULCERATIVE STOMATITIS.
Authors: JOHN S. MARSHALL
Journal: JAMA (1899)

Stomatitis is an inflammation of the mucous membrane of the mouth. All inflammatory conditions which involve the gums, the inner surfaces of the cheeks, the lips and the tongue are usually included under the general term, "stomatitis." The affections which are thus included are, with few exceptions, confined to the period of infancy and childhood. Adults seldom suffer from these affections except as manifestations of some other morbid condition. The forms of inflammation of the mouth which are most common are stomatitis simplex, stomatitis catarrhalis, stomatitis aphthosa, stomatitis parasitica and stomatitis ulcerosa. A clinical study of the inflammatory affections of the mucous membranes of the mouth will reveal in certain features a close resemblance to the inflammatory affections as they appear in the skin, while in other points they will present features which are common to inflammatory conditions of the mucous membrane in general. It has frequently been noticed, that
The Trips of Slips
Authors: Henry G. Dove
Journal: JAMA (1980)

The laboratory and x-ray studies performed on 148 outpatients were monitored to see how long it took for the results to be obtained, reviewed, and inserted into the medical record. An average of 27.0 days was required for all of these tasks. This mundane, unwieldy problem clearly deserves more attention, especially in outpatient clinics at teaching hospitals. (<i>JAMA</i>243:537-539, 1980)
The Prevalence of Esophageal Cardiac Glands: Relationship with Erosive Esophagitis and Nonerosive Reflux Disease (NERD) in Japanese Patients
Authors: K. Yagi, A. Nakamura, A. Sekine, H. Umezu
Journal: Endoscopy (2006)

Gastroesophageal reflux disease (GERD) can be classified into nonerosive reflux disease (NERD), erosive esophagitis, and Barrett’s esophagus [1]. NERD is defined as the presence of typical symptoms of GERD caused by intraesophageal acid, in the absence of endoscopically evident esophageal mucosal injury [2] [3]. The mechanism of NERD has been well studied [2] [3]. However, in a previous study we reported that yellow elevated areas in the distal squamous epithelium represent esophageal cardiac glands and that exposed esophageal cardiac glands are observed under magnification [4]. We read with great interest a recent review article describing esophageal cardiac glands [5].
Psoriatic arthritis screening tools: study design and methodologic challenges - reply from authors
Authors: L.C. Coates, T. Aslam, F. Al Balushi, A.D. Burden, E. Burden-Teh, A.R. Caperon, R. Cerio, C. Chattopadhyay, H. Chinoy, M.J.D. Goodfield, L. Kay, S. Kelly, B.W. Kirkham, C.R. Lovell, H. Marzo-Ortega, N. McHugh, R. Murphy, N.J. Reynolds, C.H. Smith, E.J.C. Stewart, R.B. Warren, R. Waxman, H.E. Wilson, P.S. Helliwell
Journal: British Journal of Dermatology (2014)

Funding sources: None. Conflicts of interest: None declared. Dear Editor, We thank Dr Qureshi et al. (‘Psoriatic arthritis screening tools: study design and methodologic challenges’)1 for their comments about our study [‘Comparison of three screening tools to detect psoriatic arthritis in patients with psoriasis (CONTEST study)’].2 The CONTEST study was carried out in dermatology clinics only. As they point out, there would be little point in administering these instruments in rheumatology clinics. The low response rate is disappointing, but reflects the likely response to the use of such tools in clinical practice. We would indicate that our sample size was almost fully achieved so the study had sufficient power to compare the three instruments. Unless Dr Qureshi et al. feel that the Psoriatic Arthritis Screening and Evaluation tool was specifically disadvantaged by the nonresponders, we can't see why the study failed to be a fair comparison of the three tools administered in the setting for which they were designed to work.
ABC of hypertension: The pathophysiology of hypertension
Authors: Gareth Beevers, Gregory Y H Lip, Eoin O'Brien
Journal: BMJ (2001)

There is still much uncertainty about the pathophysiology of hypertension. A small number of patients (between 2% and 5%) have an underlying renal or adrenal disease as the cause for their raised blood pressure. In the remainder, however, no clear single identifiable cause is found and their condition is labelled “essential hypertension”. A number of physiological mechanisms are involved in the maintenance of normal blood pressure, and their derangement may play a part in the development of essential hypertension.

This article has been adapted from the newly published 4th edition of ABC of Hypertension . The book is available from the BMJ bookshop and at http://www.bmjbooks.com/



The relative frequency of primary and secondary hypertension



It is probable that a great many interrelated factors contribute to the raised blood pressure in hypertensive patients, and their relative roles may differ between individuals. Among the factors that have been intensively studied are salt intake, obesity and insulin resistance, the renin-angiotensin system, and the sympathetic nervous system. In the past few years, other factors have been evaluated, including genetics, endothelial dysfunction (as manifested by changes in endothelin and nitric oxide), low birth weight and intrauterine nutrition, and neurovascular anomalies.

#### Physiological mechanisms involved in development of essential hypertension

Maintenance of a normal blood pressure is dependent on the balance between the cardiac output and peripheral vascular resistance. Most patients with essential hypertension have a normal cardiac output but a raised peripheral resistance. Peripheral resistance is determined not by large arteries or the capillaries but by small arterioles, the walls of which contain smooth muscle cells. Contraction of smooth muscle cells is thought to be related to a rise in intracellular calcium concentration, which may explain the vasodilatory …
Awareness of Family and Contact History of Tuberculosis in Generalized Sarcoidosis
Authors: V. Parsons
Journal: BMJ (1960)

The need for a study which includes the recording of respiratory function is emphasized.The Research Committee of the TuLberculosis Societs of Scotland wishes to express its gratituLde to the physicians, bacteiiologists, and nursing staffs of the hospitals concerned for the excellence of their co-operation.The committee is especially indebted to Dr. DoLuglas Kay, who co-ordinated the trial, and to Mrs. Joan Valentine for very considerable secretarial and statistical assistance.
Differentiating germinal center‐derived lymphomas through their cellular microenvironment
Authors: Antonino Carbone, Annunziata Gloghini, Antonello Cabras, Giuliano Elia
Journal: American Journal of Hematology (2009)

Abstract Recent studies on normal and malignant B‐cells have provided evidence that the germinal center (GC) of lymphoid follicles exerts a role in B‐cell physiology and malignancy. GC‐derived lymphomas include both B‐cell and T‐cell lymphomas. Remarkably, tumor cells of GC‐derived lymphomas proliferate in close association with cellular environment that retains key features of normal GC cellular microenvironment. Neoplastic follicles in follicular lymphoma contain, in addition to follicular dendritic cells (FDC) other non‐neoplastic cells including macrophages and GC T‐cells. In addition to aggregates of FDCs, the background infiltrate of nodular lymphocyte predominant Hodgkin lymphoma includes small B‐cells, T‐cells, and histiocytes. Typically, most of the lymphocyte predominant (LP) cells are ringed by CD3+/CD4+ T‐cells expressing CD57, PD1, BCL6, and MUM1/IRF4. By contrast, Reed–Sternberg cells of classic Hodgkin lymphoma (cHL) are surrounded by CD3+/CD4+ T‐cells expressing CD40L. Unlike cHL and other peripheral T‐cell lymphomas, the AITL microenvironment characteristically contain a prominent proliferation of high endothelial venules and FDC. Thus, these findings shed new light on the characterization of GC‐derived lymphomas and may help in the differential diagnosis and acknowledge several novel pathogenetic mechanisms on these lymphomas. Am. J. Hematol., 2009. © 2009 Wiley‐Liss, Inc.
Effects of chitin and its derivatives on the proliferation and cytokine production of fibroblasts in vitro
Authors: Takashi Mori, Masahiro Okumura, Mitsunobu Matsuura, Keisuke Ueno, Seiichi Tokura, Yoshiharu Okamoto, Sabro Minami, Toru Fujinaga
Journal: Biomaterials (1997)
Health-Related Quality-of-Life Following Modified Ureterosigmoidostomy (Mainz Pouch II) as Continent Urinary Diversion
Authors: Patrick J. Bastian, Peter Albers, Herbert Hanitzsch, Giancarlo Fabrizi, Romano Casadei, Axel Haferkamp, Stefan Schumacher, Stefan C. Müller
Journal: European Urology (2004)
Early Alzheimer's Disease
Authors: Richard Mayeux
Journal: New England Journal of Medicine (2010)

A 72-year-old man seeks consultation at the urging of his wife for increasing difficulty with memory over the past 2 years. Clients at his brokerage firm have expressed concern about his occasional lapses in memory. His wife reports that he frequently repeats questions about social appointments and becomes angry when she points this out. The physical examination is normal, but the patient has difficulty remembering elements of a brief story and difficulty in adding a small amount of change. Alzheimer's disease is suspected. How should this patient be evaluated and treated?
Semiannual surveillance is superior to annual surveillance for the detection of early hepatocellular carcinoma and patient survival
Authors: Valentina Santi, Franco Trevisani, Annagiulia Gramenzi, Alice Grignaschi, Federica Mirici-Cappa, Paolo Del Poggio, Maria Anna Di Nolfo, Luisa Benvegnù, Fabio Farinati, Marco Zoli, Edoardo Giovanni Giannini, Franco Borzio, Eugenio Caturelli, Maria Chiaramonte, Mauro Bernardi
Journal: Journal of Hepatology (2010)
A British Medical Association Lecture on THE TREATMENT OF INFANTILE PARALYSIS
Authors: A. R. Jones
Journal: BMJ (1927)

THIERE is no disease moreproductive of permanent ability in children than infantile paralysis, but fortunately mucll crippling can be prevented by well guided early ment.The malady is always among us in a sporadic form, but it is many years since we have had an epidemic parable to that which has occurred recently at Broadstairs and Leicester.
Catecholamines and local rebound in left ventricular contractile force after release of coronary artery occlusion
Authors: W. H. Newman, P. P. Mathur, R. P. Walton
Journal: Cardiovascular Research (1971)

Data obtained in open-chest dog preparations indicate the involvement of myocardial catecholamines with increased inotropism after temporary ventricular ischaemia. Reserpinization and treatment with β-adrenergic blocking agents significantly reduced the rebound contractile force recorded after release of coronary artery constricting ligatures. Simultaneously recorded rebounds in coronary arterial blood flow were not correspondingly affected.
Determination of the allergenic activity of birch pollen and apple prick test solutions by measurement of β‐hexosaminidase release from RBL‐2H3 cells. Comparison with classical methods in allergen standardization
Authors: A Hoffmann, A Jamin, K Foetisch, S May, H Aulepp, D Haustein, S Vieths
Journal: Allergy (1999)

Background: A murine in vitro model of the allergic type I reaction was set up to determine the biologic activity of extracts without involvement of human beings. It is based on β‐hexosaminidase release from passively sensitized RBL cells after allergen challenge. The intended application of this RBL cell assay in the field of quality control of allergenic extracts requires its comparison with established methods. Methods: The activity of five standardized birch‐pollen prick test solutions was determined in parallel by RBL assay, direct IgE binding, IgE‐binding inhibition, major allergen content, histamine‐release assay, and skin testing. Results: The RBL cell‐release assay corresponded well to other methods if a reagin raised against natural birch‐pollen extract was used for passive sensitization. However, in the case of a reagin against recombinant Bet v 1, only a decreased activity was observed, presumably because a reduced number of epitopes were recognized by the monospecific reagin. In contrast to standardized birch‐pollen extracts, nonstandardized apple extracts showed poor activity in all assays. Conclusions: This murine model might be a useful tool in the quality control of allergenic extracts. It combines properties of assays based on standardized antisera and of assays that consider IgE cross‐linking properties.
Oxidative stress stimulates proliferation and invasiveness of hepatic stellate cells via a MMP2-mediated mechanism
Authors: Andrea Galli, Gianluca Svegliati‐Baroni, Elisabetta Ceni, Stefano Milani, Francesco Ridolfi, Renata Salzano, Mirko Tarocchi, Cecilia Grappone, Giulia Pellegrini, Antonio Benedetti, Calogero Surrenti, Alessandro Casini
Journal: Hepatology (2005)

Experimental evidence indicates that reactive oxygen species (ROS) are involved in the development of hepatic fibrosis; they induce hepatic stellate cells (HSC) proliferation and collagen synthesis. To address the role of matrix metalloproteinase (MMP)-2 in promoting HSC proliferation during hepatic injury, we investigated whether oxidative stress modulates the growth and invasiveness of HSC by influencing MMP-2 activation. Cell invasiveness and proliferation, which were studied using Boyden chambers and by counting cells under a microscope, were evaluated after treatment with a superoxide-producing system, xanthine plus xanthine oxidase (X/XO), in the presence or absence of antioxidants and MMP inhibitors. Expression and activation of MMP-2 were evaluated via gel zymography, immunoassay, and ribonuclease protection assay. The addition of X/XO induced proliferation and invasiveness of human HSC in a dose-dependent manner. The addition of antioxidants as well as MMP-2–specific inhibitors impaired these phenomena. X/XO treatment increased MMP-2 expression and secretion appreciably and significantly induced members of its activation complex, specifically membrane-type 1 MMP and tissue inhibitor metalloproteinase 2. To study the intracellular signaling pathways involved in X/XO-induced MMP-2 expression, we evaluated the effects of different kinase inhibitors. The inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphatidyl inositol 3-kinase (PI3K) abrogated X/XO-elicited MMP-2 upregulation and completely prevented X/XO-induced growth and invasiveness of HSC. In conclusion, our findings suggest that MMP-2 is required for the mitogenic and proinvasive effects of ROS on HSC and demonstrate that ERK1/2 and PI3K are the main signals involved in ROS-mediated MMP-2 expression. (HEPATOLOGY 2005;41:1074–1084.)
Nontuberculous Mycobacteria among Patients with Cystic Fibrosis in the United States. Screening Practices and Environmental Risk
Authors: Jennifer Adjemian, Kenneth N. Olivier, D. Rebecca Prevots
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Persons with cystic fibrosis (CF) are at greater risk of nontuberculous mycobacterial (NTM) infections than the general population. However, among patients with CF, geographic variation in prevalence is poorly understood.To describe the prevalence and screening practices of NTM among U.S. patients with CF.CF Patient Registry data from 2010-2011 were obtained to estimate the prevalence of NTM among patients with CF 12 years of age or older by state. Climatic data were also obtained and predictors of NTM infection analyzed using regression analysis. Geographic clustering and mycobacterial culture rates by state were also assessed.Among patients with CF 12 years of age or older, 58% had mycobacterial cultures; 14% were positive for NTM. Most states (n = 31) had a prevalence of 10-20%; seven states predominantly in the West and Southeast had a prevalence of 20% or greater, including Alaska, which cultured patients more frequently than any other state. Nearly 60% of positive cultures were for Mycobacterium avium complex, although this ranged by state, from 29% in Louisiana to 100% for Nebraska/Delaware. Significant (P < 0.002) spatial clustering of NTM was detected, centering in Wisconsin, Arizona, Florida, and Maryland. Higher saturated vapor pressure increased risk for NTM (odds ratio = 1.06; 95% confidence interval = 1.02-1.10). The proportion of patients cultured for mycobacteria varied greatly by state of residence (median = 46%; range = 9-73%).NTM prevalence varies significantly among patients with CF by geographic area, and is largely influenced by environmental factors. However, NTM culture practices vary greatly, with some high-prevalence states screening less than 25% annually. Routine screening for all patients with CF is needed for timely detection.