tbuckley/cabot-search huggingface dataset:
P94The neuro-cardiac interaction defines an extracellular microdomain required for neurotrophic signaling
Authors: M Franzoso, T Zaglia, N Pianca, G Di Benedetto, M Sandre, V Gobbo, S Schiaffino, O Marin, R Lo Preiato, M Mongillo
Journal: Cardiovascular Research (2014)

Purpose: Sympathetic ganglia neurons (SGNs) innervate the myocardium and tune heart rate and contractility. Development and viability of cardiac neurons depend on neurotrophins that are released in low amounts by the myocardium. This study aims to understand whether the direct cell-to-cell contact plays a role in NGF-mediated signaling between cardiomyocytes (CMs) and SGNs. Methods and results: Electron microscopy and immunofluorescence on mouse heart slices and rat SGN/CM co-cultures showed a close association between SGNs and CMs, neurotransmitter vesicle accumulation, increased membrane protein density and enrichment of the NGF receptor (TrkA) at the contact site. These data support that specialized and locally organized signaling domains exist (neuro-cardiac junction, NCJ, hereafter). We tested the functional role of the NCJ in NGF-mediated prosurvival signaling. NGF expression by CMs was assessed by western blot analysis and its silencing in co-cultures caused a 66% decrease of neuronal density, suggesting that neurons depend on NGF released by CMs. NGF binding to its receptor triggers TrkA retrograde transport to neuronal soma that was monitored using fluorescently labeled TrkA. TrkA-RFP retrograde movements were faster in processes contacting CMs than other cardiac cells, further supporting that neuronal NGF signaling is activated by the coupled CMs. SGNs cultured on NGF-silenced CMs showed a 20% decrease in the NCJ area when compared to those on wild type CMs of the same culture. Moreover, NGF uptake was observed only in processes contacting NGF overexpressing CMs, supporting that neurotrophin mediated signaling is involved at the SGN/CM interaction. Consistently, cultured SGNs in contact with CMs survived NGF withdrawal, whereas neurons alone treated with CM-conditioned medium did not survive because of the very low NGF concentration (<5pg/mL). An anti-NGF antibody, a TrkA antagonist (c(92-96)) and inhibitor (k252a) were used to antagonize receptor activation by NGF. Only the small membrane permeable k252a reduced neuronal density, suggesting that the NCJ is an isolated microdomain. K252a was used to estimate NGF concentration at the contact site, which resulted about 1.5nM, four orders of magnitude higher than that in CM-conditioned medium, supporting that the NCJ allows amplification of intercellular NGF signaling. Conclusions: Taken together, our results suggest that the NGF-dependent pro-survival signal to the SGN needs a direct interaction with the CM that facilitates NGF activation of TrkA thanks to the development of an isolated microdomain characterized by a high NGF concentration.
JAMA 100 Years Ago
Authors: J. A. LARRABEE
Journal: JAMA (1988)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The Dangers of Acetanilid.
Authors: W. H. Graves
Journal: JAMA (1905)

Dodge City, Kan., July 14, 1905. <h3>To the Editor:</h3> -I was walking along the street some months ago and overtook my venerable friend, the Methodist minister, who said "Doctor, I'm glad to see you. What is antikamnia?" I told him that it is a mixture of uncertain composition, used with greater or less success for the relief of pain; that its principal constituent is acetanilid, a valuable remedy under certain conditions, but dangerous when used by the laity. The old gentleman took from his vest pocket a little square box containing twenty-five tablets of about five grains each. The box was labeled "antikamnia," and the legend declared that the remedy would cure a number of unpleasant and more or less dangerous conditions to which humanity is subject, but there was not a word to indicate the size of the dose or the frequency with which it might be repeated. The
The Utility of Serum Tryptase in the Diagnosis of Shrimp-induced Anaphylaxis
Authors: P. Wongkaewpothong, P. Pacharn, C. Sripramong, S. Boomchoo, N. Visitsunthorn, P. Vichyanond, O. Jirapongsananuruk
Journal: Journal of Allergy and Clinical Immunology (2009)
Profitable and Nonprofitable Drugs
Authors: Melvin H. Van Woert
Journal: New England Journal of Medicine (1978)

IN reaction to the thalidomide tragedy, Congress enacted the Kefauver-Harris amendments to the Food, Drug and Cosmetics Act in 1962 that considerably increased the number of preclinical and clinical tests required by the Food and Drug Administration (FDA) before release of a drug for marketing. The Kefauver-Harris amendments have had profound effects on the development of new drugs. Over the years since 1962, the consumer has been protected from potentially dangerous drugs that might have reached the marketplace under the FDA legislative acts of 1906 and 1938. However, the consumer protection has not been gained without adverse consequences. A major . . .
The Cost to Health Plans of Poor Glycemic Control
Authors: Todd P Gilmer, Patrick J O'Connor, Willard G Manning, William A Rush
Journal: Diabetes Care (1997)

OBJECTIVE We tested the hypothesis that level of glycemic control is related to medical care costs in adults with diabetes. RESEARCH DESIGN AND METHODS Regression analysis was used to estimate the relationship between glycemic control and medical care charges for 3,017 adults with diabetes who were continuously enrolled in a large health maintenance organization (HMO) over a 4-year period. Diagnosis of diabetes was ascertained from diagnostic and pharmaceutical databases using a method with an estimated sensitivity of 0.91 and an estimated specificity of 0.99. Charges for care included defined outpatient and inpatient services. Patients who disenrolled or who died during the 4-year period were excluded from the main analysis. RESULTS Charges for medical care for patients with diabetes from 1993 to 1995 were closely related to HbA1c level in 1992 before and after adjustment for age, sex, coronary heart disease, and hypertension. Standardized 3-year estimates of charges ranged from $10,439 for patients without comorbid conditions to $44,417 for those with heart disease and hypertension. Medical care charges increased significantly for every 1% increase above HbA1c of 7%. For a person with an HbA1c value of 6%, successive 1% increases in HbA1c resulted in cumulative increases in charges of ∼ 4, 10, 20, and 30%. The increase in charges accelerated as the HbA1c value increased. For patients with diabetes only, or with diabetes plus other chronic conditions, the rate of increase in charges with HbA1c was consistent. CONCLUSIONS HbA1c provides useful information to providers and patients regarding both health status and future medical care charges. Economic data suggest that clinicians should assign high importance to low HbA1c results and aggressively maintain the HbA1c status of patients who have low HbA1c values. For economic as well as clinical reasons, it may be beneficial to lower HbA1c when it is &amp;gt; 8% and to reduce cardiovascular risk factors. The medical charge data suggest that investment in clinical systems to improve diabetes care may benefit both payers and patients.
Control of a key transition from prostrate to erect growth in rice domestication
Authors: Lubin Tan, Xianran Li, Fengxia Liu, Xianyou Sun, Chenggang Li, Zuofeng Zhu, Yongcai Fu, Hongwei Cai, Xiangkun Wang, Daoxin Xie, Chuanqing Sun
Journal: Nature Genetics (2008)
Autonomic and peripheral (sensorimotor) neuropathy in chronic liver disease: A clinical and electrophysiologic study
Authors: Vinay Chaudhry, Andrea M. Corse, Richard O'Brian, David R. Cornblath, Andrew S. Klein, Paul J. Thuluvath
Journal: Hepatology (1999)

Peripheral neuropathy has been reported in association with chronic liver disease. However, the precise incidence, severity and characteristics of neuropathy, and the relationship of neuropathy to different etiologies of liver disease have not been defined. In this study, 58 patients with advanced liver disease were evaluated in detail for the presence of neuropathy. Peripheral (sensorimotor) neuropathy was found in 71% and autonomic neuropathy was found in 48% of the patients. Although the majority of patients were asymptomatic, neurological examination showed distal sensory loss to pain, or vibration or distal loss of reflexes in 17 patients (29%). Sensory neuropathy was seen more commonly than motor axonal polyneuropathy on nerve conduction studies. Quantitative sensory testing was frequently abnormal (62%) and cooling thresholds were more affected than vibration thresholds. Overall, the pattern of neuropathy in patients with liver disease conformed to the pattern expected in "dying back" or length-dependent neuropathy. The neuropathy was most severe in patients with advanced hepatic decompensation. Comparison of causes of liver disease showed no significant differences in the severity of neuropathy among the different etiologies. In conclusion, axonal sensory-motor polyneuropathy and autonomic neuropathy are commonly seen in patients with end-stage liver disease of different causes.
Pulsatile Stretch in Coronary Arteries Elicits Release of Endothelium-Derived Hyperpolarizing Factor
Authors: Rüdiger Popp, Ingrid Fleming, Rudi Busse
Journal: Circulation Research (1998)

Abstract —To date, the release of the endothelium-derived hyperpolarizing factor (EDHF) has been demonstrated only in response to receptor-dependent Ca 2+ -elevating agonists. Since endothelial cells in situ are continuously subjected to rhythmic distension, we investigated the effect of rhythmic stretch on the release of EDHF from isolated porcine coronary arteries. In the combined presence of diclofenac and N G -nitro- l -arginine (L-NNA), sinusoidal pressure oscillations (from 40 to 50 mm Hg, 4 minutes, 1.5 Hz) led to simultaneous oscillations in the external diameter of coronary artery segments, the amplitude of which were decreased by iberiotoxin and apamin and also by endothelial denudation. In order to directly demonstrate the release of EDHF, the intraluminal solution from endothelium-intact coronary segments exposed to pulsatile stretch was applied to detector rat aortic smooth muscle cells, the membrane potential of which was continuously measured using the patch-clamp technique. The hyperpolarization of detector cells induced by the intraluminal solution was proportional to the amplitude of the pressure oscillations applied to the donor artery and was attenuated by either preincubation of donor arteries with 17-octadecynoic acid or application of either tetrabutylammonium or iberiotoxin to detector cells. In contrast to the bradykinin-induced release of EDHF, the EDHF synthesized in response to pulsatile stretch did not exhibit any tachyphylaxis. These findings demonstrate for the first time that the synthesis of EDHF in coronary arteries can be mechanically stimulated by rhythmic vessel wall distension and suggest that the continuous release of EDHF may contribute to the adjustment of an adequate vascular compliance and to the control of coronary blood flow.
Polyneuropathy after perhexiline maleate therapy.
Authors: F Lhermitte, M Fardeau, F Chedru, J Mallecourt
Journal: BMJ (1976)

Polyneuropathy after perhexiline maleate therapyThough generally considered not to cause serious side effects perhexiline maleate may occasionally cause hypoglycaemia,5 severe hepatic dysfunction,2 or peripheral neuropathy.' 4This paper is the first to report the histclogical findings in a case of neuropathy due to this drug.Case report
Poisonous and Venomous Marine Animals of the World
Authors: S. M. Rabson
Journal: JAMA (1967)

Sponsored by the Department of Defense and handsomely gotten out by the Government Printing Office, the first volume is now available. For almost a quarter-century, its author, a physician, has been preparing the work, initially to be limited to fishes, but now devoted to all marine life, from protozoa to turtles. During a preliminary phase (14 years), 30 major expeditions and field trips were made to many places, from the Carolinas to the Mediterranean. As the preface states, thousands of histologic sections were made of venom organs and 25,000 fish samples screened for toxicity. Volume 1 ranges from protozoa to platyhelminths; the other volumes, promised for 1967 and 1968, will be devoted to fishes, sea snakes, turtles, etc. For whom is the work intended? To begin with, any lover of natural history, especially if he enjoys numerous and striking photographs, both in black-and-white and in color. For the dermatologist, particularly
PLASMA PROTEIN FORMATION IN VITRO BY TISSUES FROM MICE INFECTED WITH STAPHYLOCOCCI
Authors: Curtis A. Williams, Richard Asofsky, G. Jeanette Thorbecke
Journal: The Journal of Experimental Medicine (1963)

Isotopic labeling of plasma proteins in vitro by tissues from staphylococcal-infected and control mice was examined, using autoradiography of immunoelectrophoretic patterns. The results indicate that in infected animals there is hyperactivity of liver tissue in producing albumin, α- and ß-globulins, and of spleen tissue in producing immune globulins. The observed increase in labeling of some proteins by tissues from infected mice is to a large extent correlated with an increase of these proteins in the serum.
Relational priming plays a supporting but not leading role in adult analogy-making
Authors: Alexander A. Petrov
Journal: Behavioral and Brain Sciences (2008)

Abstract Leech et al.'s analysis adds to an emerging consensus of the role of priming in analogy-making. However, their model cannot scale up to adult-level performance because not all relations can be cast as functions. One-size-fits-all accounts cannot capture the richness of analogy. Proportional analogies and transitive inferences can be made by nonstructural mechanisms. Therefore, these tasks do not generalize to tasks that require structure mapping.
Absorption of Bile Pigments by the Gall Bladder*
Authors: J. Donald Ostrow
Journal: Journal of Clinical Investigation (1967)

A technique is described for preparation in the guinea pig of an in situ, isolated, vascularized gall bladder that exhibits normal absorptive functions. Absorption of labeled bile pigments from the gall bladder was determined by the subsequent excretion of radioactivity in hepatic bile. Over a wide range of concentrations, unconjugated bilirubin-(14)C was well absorbed, whereas transfer of conjugated bilirubin proceeded slowly. Mesobilirubinogen-(3)H was absorbed poorly from whole bile, but was absorbed as rapidly as unconjugated bilirubin from a solution of pure conjugated bile salt. Bilirubin absorption was not impaired by iodoacetamide, 1.5 mM, or dinitrophenol, 1.0 mM, even though water transport was affected. This indicated that absorption of bilirubin was not dependent upon water transport, nor upon energy-dependent processes. The linear relationship between absorption and concentration of pigment at low concentrations in bile salt solutions suggested that pigment was transferred by passive diffusion. At higher pigment concentrations or in whole bile, this simple relationship was modified by interactions of pigment with bile salts and other constituents of bile. These interactions did not necessarily involve binding of bilirubin in micelles. The slow absorption of the more polar conjugates and photo-oxidative derivatives of bilirubin suggested that bilirubin was absorbed principally by nonionic, and partially, by ionic diffusion. Concentrations of pure conjugated bile salts above 3.5 mM were found to be injurious to the gall bladder mucosa. This mucosal injury did not affect the kinetics of bilirubin absorption. During in vitro incubation of bile at 37 degrees C, decay of bilirubin and hydrolysis of the conjugate proceeded as first-order reactions. The effects of these processes on the kinetics of bilirubin absorption, and their possible role in the formation of "white bile" and in the demonstrated appearance of unconjugated bilirubin in hepatic bile, are discussed.
Retrospective study of 1000 deaths from injury in England and Wales
Authors: I D Anderson, M Woodford, F T de Dombal, M. Irving
Journal: BMJ (1988)

One thousand consecutive deaths from injury in 11 coroner9s districts in England and Wales were reviewed by four independent assessors, who studied necropsy reports to identify deaths in hospital that might have been preventable. Of 514 patients admitted to hospital alive, 102 deaths (20%) were judged by all four assessors to have been potentially preventable. When those cases in which three out of four assessors considered that the death was preventable were added the total rose to 170 (33%). Nearly two thirds of all non-central nervous system deaths were judged to have been preventable. The median age of the 170 patients whose deaths were preventable was 41, and the mean Injury Severity Score was 29. Further analysis suggested that the preventable deaths were principally the result of failure to stop bleeding and prevent hypoxia and the absence of, or delay in, surgical treatment. The results closely parallel those from similar studies from the United States and suggest that there are serious deficiencies in the services for managing severe injury in England and Wales. Debate is needed now on how to correct these deficiencies. In particular, the place of trauma centres must be considered.
Venous Thrombosis, Pulmonary Embolism, and Varicose Veins
Authors: Robert R. Linton
Journal: JAMA (1963)

Venous thrombosis of the lower extremity can be a crippling disease and, if pulmonary embolism results, it may be fatal. The incidence of this condition has been greatly reduced in the past decade because of a better understanding of some of the etiological factors, so that more adequate prophylactic measures may now be carried out. For practical purposes, venous thrombosis or, as some term it, thrombophlebitis, may involve both the superficial and the deep veins of the lower extremities. Early in the course of the disease the signs of inflammation, which many doctors think necessary for the diagnosis, may be absent. This is especially true when the deep venous system is involved. As a result of this absence, the term "bland" or "silent venous thrombosis" has come into use to describe this stage of the disease. Others have called this type phlebothrombosis, but this term is not so descriptive.
Hemodynamic Benefit of Atrial Pacing in Right Ventricular Myocardial Infarction
Authors: ERIC J. TOPOL
Journal: Annals of Internal Medicine (1982)

Right ventricular and inferior-posterior myocardial infarctions in four patients were complicated by low-output syndrome unresponsive to increasing intravascular volume. Ventricular pacing was started because of bradyarrhythmias, but failed to increase cardiac output; atrial pacing at identical rates resulted in dramatic increases in cardiac output. The importance of atrial contribution to ventricular function, as well as the role of the pericardium in this clinical setting, are discussed. In treating right ventricular myocardial infarction, atrial or atrioventricular sequential cardiac pacing may be preferable to ventricular pacing.
Influence of the HLA-DRbeta shared epitope on susceptibility to and clinical expression of rheumatoid arthritis in Chilean patients
Authors: A. Gonzalez, S. Nicovani, L. Massardo, V. Aguirre, V. Cervilla, J. S Lanchbury, S. Jacobelli
Journal: Annals of the Rheumatic Diseases (1997)

<h3>OBJECTIVE</h3> To analyse the influence of shared epitope positive HLA-DRB1 alleles (QKRAA or QRRAA) ) on rheumatoid arthritis (RA) susceptibility and severity in Chileans, a population that exhibits a weak association with HLA-DR4. <h3>METHODS</h3> Prevalence of alleles DRB1*01 and DRB1*04 alleles was determined by polymerase chain reaction amplification and sequence specific oligonucleotide hybridisation in 129 RA patients with defined clinical features and in 97 healthy controls. <h3>RESULTS</h3> The shared epitope was found in 70 (54%) of the RA patients and in 29 (30%) of controls (odds ratio (OR) =3; 95% confidence intervals (CI) = 1.5, 5.1; p = 0.0004), and was present in a double dose in 20% of patients versus 4% of controls (OR = 6; 95% CI = 2, 21; p = 0.0009). HLA-DRB1*0403 was the most prevalent DR4 subtype in controls (19%). HLA-DRB1*0404 or *0408 were the alleles most prominently associated with RA, 19% versus 6 % in controls (OR=3; 95% CI = 1.3, 10; p = 0.01). The risk of RA in those carrying a double dose of the shared epitope was 7.5 times that seen in patients lacking the epitope. Disease severity was moderate: 33% had extra-articular manifestations. The double dose was associated with an increased risk of vasculitis or extra-articular manifestations. However, 59 patients (46%) did not carry the shared epitope and 18 of them (31%) had extra-articular manifestations. <h3>CONCLUSIONS</h3> The weak association of RA with DR4 in Chileans seems to relate to a relatively high frequency of the DRB1*0403 allele among DR4 subtypes. As in other populations, the shared epitope in double dose is associated with RA development, especially in its more severe forms. However, both development and expression of severe forms of the disease were independent of the shared epitope in a high proportion of patients, thus emphasising the genetic heterogeneity of the disease and the possible involvement of other genetic elements.