tbuckley/cabot-search huggingface dataset:
Autonomic control of colonic tone and the cold pressore test.
Authors: M J Ford, M Camilleri, M J Joyner, R B Hanson
Journal: Gut (1996)

BACKGROUND: Cardiovascular responses to cold stimulation are well characterised. It is unclear, however, whether cold pain stimulates responses in colonic tone in the transverse and sigmoid regions. AIMS: To assess the effects of cold stimulation on tone nd motility in the transverse and sigmoid colon and on cardiovascular autonomic activity. METHODS: Phasic and tonic motility of the transverse and sigmoid colon, pulse rate, and beat to beat pulse variability (which are measures of centrally mediated changes in autonomic function) were measured before, during, and after a standard cold pressor test in 22 healthy volunteers. RESULTS: Cold pain induced a significant increase in colonic tone but not phasic contractility in the transverse and sigmoid regions. Simultaneously, cold pain increased pulse interval variability. CONCLUSION: The findings are consistent with the hypotheses that cold pain produces coactivation of both the sympathetic and parasympathetic limbs of the autonomic nervous system and that cold induced changes in colonic tone are temporally associated with alterations in central autonomic nervous activity.
Rabbit aorta and human atherosclerotic lesions hydrolyze the sphingomyelin of retained low-density lipoprotein. Proposed role for arterial-wall sphingomyelinase in subendothelial retention and aggregation of atherogenic lipoproteins.
Authors: S L Schissel, J Tweedie-Hardman, J H Rapp, G Graham, K J Williams, I Tabas
Journal: Journal of Clinical Investigation (1996)

Aggregation and retention of LDL in the arterial wall are key events in atherogenesis, but the mechanisms in vivo are not known. Previous work from our laboratories has shown that exposure of LDL to bacterial sphingomyelinase (SMase) in vitro leads to the formation of LDL aggregates that can be retained by extracellular matrix and that are able to stimulate macrophage foam cell formation. We now provide evidence that retained LDL is hydrolyzed by an arterial-wall SMase activity. First, we demonstrated that SMase-induced aggregation is caused by an increase in particle ceramide content, even in the presence of excess sphingomyelin (SM). This finding is compatible with previous data showing that lesional LDL is enriched in SM, though its ceramide content has not previously been reported. To address this critical compositional issue, the ceramide content of lesional LDL was assayed and, remarkably, found to be 10-50-fold enriched compared with plasma LDL ceramide. Furthermore, the ceramide was found exclusively in lesional LDL that was aggregated; unaggregated lesional LDL, which accounted for 20-25% of the lesional material, remained ceramide poor. When [3H]SM-LDL was incubated with strips of rabbit aorta ex vivo, a portion of the LDL was retained, and the [3H]SM of this portion, but not that of unretained LDL, was hydrolyzed to [3H]ceramide by a nonlysosomal arterial hydrolase. In summary, LDL retained in atherosclerotic lesions is acted upon by an arterial-wall SMase, which may participate in LDL aggregation and possibly other SMase-mediated processes during atherogenesis.
Responses of 6- and 9-months-old Infants to Two and Three Doses of Poliomyelitis Vaccine
Authors: F. T. Perkins, R. Yetts, W. Gaisford
Journal: BMJ (1959)

MEDICALJOURNALdeoxycortone acetate used in this work during the past four years, and Boots Pure Drug Co. for donations of cortisone and heparin.We are much indebted to the members of our Unit-Messrs.J. Coghlan, B.Sc., J. Blair-West, B. Dyzenhaus, J. Sabine, B.Ag.Sci., and P. Gardner for their enthusiastic participation, including overnight and week-
Abstract 1039: Histone deacetylase 8 (HDAC8) target identification and mechanism of action of HDAC8 isoform-specific inhibitors
Authors: Sriram Balasubramanian, Mint Sirisawad, Susanne Steggerda, Chitra Mani, Patti Thiemann, Joseph J. Buggy
Journal: Cancer Research (2012)

Abstract HDAC8 is a member of the histone deacetylase family, but no acetylation target in cells has yet been identified. Due to a different pocket structure, most of the pan-HDAC inhibitors currently in the clinic bind poorly to it. HDAC8 knockout mice were shown to have an embryonic defect in neural crest development, but the adult mice have no other published phenotype, and its functions in adult normal or tumor cells are not well understood. In this work, we have undertaken extensive cellular and tissue localization studies, knockdown and isoform-specific inhibition studies, whole genome expression profiling, proteomics experiments to identify differentially acetylated and expressed proteins, and kinome siRNA knockdown experiments to identify pathways of activity. In total, these results point to HDAC8's essential function in many tumor cell types, not all of which are dependent upon the enzymatic activity of the enzyme. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1039. doi:1538-7445.AM2012-1039
Thymidylate Synthase Expression in Gastroenteropancreatic and Pulmonary Neuroendocrine Tumors
Authors: Paolo Ceppi, Marco Volante, Anna Ferrero, Luisella Righi, Ida Rapa, Rosj Rosas, Alfredo Berruti, Luigi Dogliotti, Giorgio V. Scagliotti, Mauro Papotti
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The predictive role of the quantification of thymidylate synthase (TS) in tumors treated with antifolate drugs, such as 5-fluorouracil (5-FU), has been extensively reported in a variety of human tumors. Neuroendocrine tumors (NET) represent potential targets of antifolate agents, but no data on TS expression level in these tumors are currently available. Experimental Design: A series of 116 NETs were collected, including 58 gastroenteropancreatic (GEP) and 58 lung NETs. In 24 well-differentiated GEP neuroendocrine carcinomas (WD-NEC), a 5-FU–based treatment was given. Total RNA was extracted from microdissected paraffin blocks. TS mRNA quantification was done by real-time PCR, whereas protein expression was evaluated by immunohistochemistry. Results: By means of both quantification by real-time PCR and immunohistochemistry, a higher TS expression in pulmonary small cell lung cancer and large cell NEC compared with typical and atypical carcinoids was observed (P &amp;lt; 0.01). Similarly, in GEP tumors, a higher TS expression in poorly differentiated carcinomas than both WD-NEC and benign tumors (P &amp;lt; 0.01) was found. In patients with WD-NEC treated with 5-FU, high TS mRNA levels were associated with shorter time to progression (P = 0.002) and overall survival (P = 0.04). This negative prognostic role was confirmed in multivariate analysis adjusting for major prognostic variables (P = 0.01). No association between TS mRNA and survival was observed in WD-NEC patients not receiving 5-FU. Conclusions: This study, for the first time, (a) reports the differential TS expression in the spectrum of NETs and (b) indicates TS as a possible predictive marker of treatment efficacy in WD-NEC patients treated with 5-FU.
RANTES induces tyrosine kinase activity of stably complexed p125FAK and ZAP-70 in human T cells.
Authors: K B Bacon, M C Szabo, H Yssel, J B Bolen, T J Schall
Journal: The Journal of Experimental Medicine (1996)

The chemokine RANTES is a chemoattractant and activating factor for T lymphocytes. Investigation of the signal transduction mechanisms induced by RANTES in T cells revealed tyrosine phosphorylation of multiple protein species with prominent bands at 70-85 and 120-130 kD. Immunoprecipitation and Western analyses revealed that a protein of 125 kD was identical to the focal adhesion kinase (FAK) pp125FAK. RANTES stimulated phosphorylation of FAK as early as 30 seconds and immunoblots using antiphosphotyrosine monoclonal antibodies revealed that there was consistent phosphorylation of a 68-70 kD species in the pp125FAK immunoprecipitates. Immunoblotting and kinase assays showed this to be two separate proteins, the tyrosine kinase zeta-associated protein (ZAP) 70, and the focal adhesion protein paxillin. These results indicate a potentially important role for RANTES in the generation of T cell focal adhesions and subsequent cell activation via a molecular complex containing FAK, ZAP-70, and paxillin.
Promotion of colorectal neoplasia in experimental murine ulcerative colitis.
Authors: I Okayasu, T Ohkusa, K Kajiura, J Kanno, S Sakamoto
Journal: Gut (1996)

The mechanisms underlying the frequent development of colorectal carcinomas in patients with ulcerative colitis are still unknown.To evaluate whether mucosal necrosis and regeneration act as enhancing or promoting factors in colorectal tumorigenesis, development of multiple colorectal tumours was studied in a murine model of ulcerative colitis with azoxymethane pretreatment.Periods of chronic ulcerative colitis in mice were induced by three repeated administrations of 3% dextran sulphate sodium subsequent to a single azoxymethane pretreatment, to give conditions similar to the clinically observed active and remission phases.In the chronic colitis group with carcinogen exposure, multiple mucosal tumours (10.5/mouse) developed in the colorectum. This occurred primarily on the left side of the large intestine or transverse colon, the sites of the most severe colitic injury. The observed lesions were high grade dysplasias and invasive adenocarcinomas. Increased cell proliferation was evidenced by high uptake of bromodeoxyuridine, and increased activities of thymidylate synthetase and thymidine kinase. No tumours were induced in the control groups with azoxymethane pretreatment or chronic colitis alone.Repeated mucosal erosion with necrosis and regeneration is critical for the development of colorectal tumours in this experimental colitis system.
NATIONAL MEDICAL LEGISLATION.
Authors: JAMES T. GREELEY
Journal: JAMA (1897)

I have the honor to address you on this occasion in behalf of action, already initiated, well-advanced and generally approved by you and by the profession of this and of foreign countries, because it is designed and calculated to raise the character of the profession, to exalt the capacity of those on whom the welfare of all mankind rests, to weed out or fitly qualify those empirics who are at once the bane of medicine and the terrible foes of social health and of all prosperity. The intention is necessary, is wise, practical and permanent. Its propriety is demonstrated as well by the notorious evil against which it is leveled as it is by the patent values of the purposes for which it is framed. Wherever attempted it has been crowned and laureled both by popular and professional approval. It appeals to all who desire health for themselves or others;
Surgery for Cerebrovascular Insufficiency (Stroke): With Special Emphasis on Carotid Endarterectomy
Authors: Oscar Sugar
Journal: JAMA (1969)

Analysis of 595 carotid artery operations in 466 patients leads to the conclusion that endarterectomy can increase cerebral blood flow and relieve manifestations of cerebral vascular insufficiency in many, but not all, cases. Differentiations are made between frank stroke (including reversible ischemic neurologic deficit), transient cerebral ischemia (no residues after 24 hours), and chronic cerebral ischemia. Emergency operation should not be done in the acute stage of profound stroke, rapidly progressing or rapidly improving stroke, if postoperative deaths are to be avoided. Total carotid occlusion may be operated on if the patient is seen in the first 6 to 12 hours. Patients with asymptomatic bruits may well be considered for angiography, and if significant lesions are found, endarterectomy may prevent future strokes. A final chapter considers briefly surgery of the aortic arch and vertebral vessels. For the most part, the pictures are apropos and well reproduced. Technical details are not
AN UNUSUAL ORBITAL TUMOR
Authors: WALTER SCOTT FRANKLIN
Journal: JAMA (1922)

In this paper we present the clinical history and microscopic findings of an unusual case of orbital tumor. The diagnosis was not made clinically, nor can one be ventured at present. <h3>REPORT OF CASE</h3><h3>History.</h3> —C. L., a man, aged 30, was referred to the university hospital from the outpatient department because of an unusual orbital tumor of the left side. There was nothing of note in the family history; no trace of familial tuberculosis, carcinoma, heart, kidney or mental disease. The patient was born in California, and had spent most of his life there. He was a street-car conductor. He had measles at 9 and a severe bronchitis at 20 which had left him with a chronic nasal catarrah and asthma; otherwise he had always been in good health. Venereal diseases were denied. His habits were good. He had a tumor of the left cheek removed five years before;
Antiperinuclear and anti-RA33 antibodies in juvenile chronic arthritis.
Authors: G Nesher, V K Wilson, T L Moore, T G Osborn, V E Hanna
Journal: Annals of the Rheumatic Diseases (1994)

large joints of the lower extremity.Synovial fluid eosinophilia has been noted, but only infrequently.4Although the arthritis is self- limited in most patients, it often recurs and may eventually become chronic.In contradistinction to ReA associated with bacterial infections, the majority of patients have no constitutional symptoms or other signs of filariasis.In this patient, the clinical picture was most consistent with ReA associated with filariasis.Although she did have other parasites in her stool, their association with the arthritis is militated against by the lack of gastrointestinal symptoms as well as the failure to respond to specific therapy.Eosinophils are infrequently noted in the synovial fluid.When present, they typically constitute less than 2% of leukocytes.5More pronounced synovial fluid eosinophilia has been reported in association with various rheumatological, infectious, allergic and malignant diseases.However, absolute synovial eosinophil counts above 10 000/mm3 are exceedingly rare, having been reported to date in one case of idiopathic transient synovitis,6 and two cases of Lyme disease.5It might be unexpected for eosinophilia to be associated with ReA.The antigen specific T cells in the synovium of ReA patients described to date have been predominantly of the THI phenotype, which secrete primarily IL-2 and IFN-y.2On the other hand, eosinophilia is more commonly associated with activation of T cells of the TH2 phenotype, which produce primarily IL-4 and IL-5.Because IL-5 promotes the differentiation as well as the survival of eosinophils, it may be critical to conditions associated with eosinophilia.7This report demonstrates that ReA associated with filariasis may be associated with massive synovial eosinophilia.This association raises the hypothesis that in some instances, in particular those associated with eosinophilia, ReA might be mediated by T cells of a TH2 phenotype.
Association between a T cell receptor restriction fragment length polymorphism and systemic lupus erythematosus.
Authors: J G Tebib, J Alcocer-Varela, D Alarcon-Segovia, P H Schur
Journal: Journal of Clinical Investigation (1990)

The present study was designed to test the possibility that T cell receptor genes are associated/linked to those involved in systemic lupus erythematosus (SLE). Genomic DNA was isolated from 31 unrelated Caucasian SLE patients, 34 unrelated Caucasian normals, 5 multiplex American Caucasian SLE families, 9 multiplex Mexican SLE families, and 13 unrelated Mexican normals. The DNA was digested with Pst I, electrophoresed, and transferred to membranes by the Southern blot method. The blots were probed with a cDNA probe for the alpha chain of the T cell receptor. 13 polymorphic RFLP patterns were recognized. 1.3- and 3.0-kb band pairs were observed in 15 of 31 of American Caucasian patients and 4 of 34 American Caucasian controls (chi square, 8.81; P less than 0.002; relative risk, 7); there was no association of any RFLP pattern with Mexican SLE. The cDNA probe was cut with Rsa I, EcoR I, and Ava II into fragments corresponding to the V, J, C, and 3'UT regions. Only the fragment corresponding to the constant region reacted with the 1.3/3.0-kb band pair. These observations suggest that a genetic marker of the constant region of the alpha chain of the T cell receptor is associated with genes involved in SLE.
Cardioprotective Effects of the Na <sup>+</sup> /H <sup>+</sup> Exchange Inhibitor Cariporide in Patients With Acute Anterior Myocardial Infarction Undergoing Direct PTCA
Authors: Hans-Jürgen Rupprecht, Jürgen vom Dahl, Wolfram Terres, Karl Melchior Seyfarth, Gert Richardt, Heinz-Peter Schultheiß, Michael Buerke, Florence H. Sheehan, Helmut Drexler
Journal: Circulation (2000)

Background —Activation of Na + /H + exchange in myocardial ischemia and/or reperfusion leads to calcium overload and myocardial injury. Experimental studies have shown that Na + /H + exchange inhibitors can attenuate Ca 2+ influx into cardiomyocytes. We therefore performed a multicenter, randomized, placebo-controlled clinical trial to test the hypothesis that inhibition of Na + /H + exchange limits infarct size and improves myocardial function in patients with acute anterior myocardial infarction (MI) treated with direct PTCA. Methods and Results —One hundred patients were randomized to receive placebo (n=51) or a 40-mg intravenous bolus of the Na + /H + exchange inhibitor cariporide (HOE 642) (n=49) before reperfusion. Global and regional left ventricular functions were analyzed by use of paired contrast left ventriculograms performed before and 21 days after PTCA and myocardial enzymes (ie, creatine kinase [CK], CK-MB, and LDH) as markers for myocardial tissue injury were evaluated. At follow-up, the ejection fraction was higher (50% versus 40%; P &lt;0.05) and the end-systolic volume was lower (69.0 versus 97.0 mL; P &lt;0.05) in the cariporide group. Significant improvements in some indices of regional wall motion abnormalities were observed, such as the percentage of chords with hypokinesis &lt; −2 SD ( P =0.045) and the severity of hypokinesis in the border zone of the infarct region ( P =0.052). In addition, CK, CK-MB, or LDH release was significantly reduced in the cariporide patients. Conclusions —Our findings suggest that inhibition of Na + /H + exchange by cariporide may attenuate reperfusion injury and thereby improve the recovery from left ventricular dysfunction after MI.
Appropriate Confusion Over `Brain Death'
Authors: Daniel Wikler
Journal: JAMA (1989)

Youngner et al<sup>1</sup>report in this issue ofThe Journalthat even the experts are having trouble understanding the concept of "brain death." More than one third of surveyed physicians responsible for identifying "brain dead" patients and declaring them dead were unable to identify irreversible loss of all brain function as the criterion of death and to apply it to two simple cases. The same was true of nearly three fourths of another group of medical residents, anesthesiologists, and nurses who work in the areas of intensive care and transplantation. Those surveyed varied widely in their concepts of death. These results are troubling, coming as they do 8 years after publication of the President's Commission report,<sup>2</sup>which formulated and argued for a whole-brain definition of death endorsed by the American Medical Association and the American Bar Association and subsequently enacted by most state legislatures. Care must be taken
Multiple Hodgkin lymphoma–associated loci within the HLA region at chromosome 6p21.3
Authors: Loukas Moutsianas, Victor Enciso-Mora, Yussanne P. Ma, Stephen Leslie, Alexander Dilthey, Peter Broderick, Amy Sherborne, Rosie Cooke, Alan Ashworth, Anthony J. Swerdlow, Gilean McVean, Richard S. Houlston
Journal: Blood (2011)
SUBSEQUENT COURSE OF A CASE OF ADDISON'S DISEASE
Authors: LEONARD G. ROWNTREE
Journal: JAMA (1922)

Under the heading, "An Autograph History of a Case of Addison's Disease," the late Dr. A. L. Muirhead<sup>1</sup>gave an unusually interesting description of the clinical course of his own illness. In this report we find a professor of pharmacology investigating and recording the subjective and objective results of treatment on himself, and the effects of drugs on the course of Addison's disease, from which he suffered and eventually died. I will record the course of events subsequent to his report, which covered his illness until December, 1920. <h3>CLINICAL COURSE</h3> Dr. Muirhead left the Mayo Clinic, Aug. 11, 1920, and for several months continued to improve. The pigmentation had almost disappeared, and he was able to resume his work as professor of pharmacology in Creighton Medical School. Improvement continued until Jan. 25, 1921, when there developed a gastric upset, loss of appetite, abdominal discomfort and weakness, accredited by Dr.
Poisoning From Ingestion of a Stramonium-Belladonna Mixture
Authors: Stephen R. Goldsmith
Journal: JAMA (1968)

Asthmador (a stramonium-belladonna mixture) caused poisoning in two individuals. At a time when Asthmador ingestion is becoming increasingly popular as a hallucinogen, it is well to include it in the differential diagnosis of acute psychotic reactions. The clinical picture may be similar to that of a lysergic acid diethylamide (LSD) psychosis. However, the<i>marked</i>pupillary dilatation, failure of the pupils to accommodate, and tachycardia seen with intoxication from Asthmador may be helpful in making the differential diagnosis.
Peak cardiac output in trained males
Authors: Z J Schlader, T Mundel, M J Barnes, L D Hodges
Journal: British Journal of Sports Medicine (2010)

Previous investigations into peak cardiac power output (CPO peak ) have been limited to clinical populations and healthy, but nonathletic adults, and normative data on trained individuals would allow a greater understanding of this parameter. Following ethics approval, eight healthy, well-trained male cyclists were recruited. Peak oxygen consumption (VO 2peak ) was assessed using an incremental ergometer test, and after a 40-min recovery period, peak cardiac output (QT peak ) was measured during a constant load test that elicited VO 2peak (±5%) using the Defares CO 2 rebreathing technique. CPO peak was calculated (CPO peak=MAP×QT×K, where mean arterial pressure (MAP) is given in mm Hg, QT in l/min, and K is the conversion factor 2.22×10-3, which expresses the output in watts (W)). Mean (SD) values during the constant load test were: VO 2peak , 4.94±0.41 l/min; QT peak , 36.5±3.7; mean arterial pressure, 123±8 mm Hg and CPO peak , 9.9±1.0 W. These results demonstrate CPO peak in a well-trained population to be approximately twice that observed in healthy, but nonathletic adults. The current data provide useful information regarding the upper limits and possible “trainability” of cardiac pumping capacity for sedentary and clinically compromised individuals.
Antihypertensive Treatment of Patients With Cardiovascular Disease but Without Hypertension
Authors: Varna Taranikanti, Yajanavalka Banerjee
Journal: JAMA (2011)

To the Editor: The meta-analysis by Ms Thompson and colleagues showed that antihypertensive treatment of patients with a history of cardiovascular disease (CVD) but without hypertension reduces cardiovascular morbidity and mortality.1 Two key issues need to be examined.
Microcomputers in epidemiological study
Authors: J. R Whittington
Journal: BMJ (1983)

pethidine.There has been no case of bradycardia in the recovery period, no matter which analgesic was administered.Pethidine was chosen for premedication because it achieves some anti- cholinergic effects without giving the patient an unduly dry, malodorous mouth.If the pulse rate is 60/min or less at induction atropine is given intravenously.