tbuckley/cabot-search huggingface dataset:
Relative roles of metabolism and renal excretory mechanisms in xenobiotic elimination by fish.
Authors: J B Pritchard, J R Bend
Journal: Environmental Health Perspectives (1991)

Renal clearance techniques were used to examine the relative contributions of metabolism and renal tubular transport in determining the rates of excretion of benzo(a)pyrene (BaP) and several of its phase I metabolites by southern flounder, Paralichthys lethostigma. Each compound (3H-labeled) was injected at a dose of 2.5 mumole/kg, producing plasma concentrations of 1 to 5 microM. Despite extensive plasma binding (greater than 95%), the uncorrected renal clearance of BaP-7,8-dihydrodiol exceeded the glomerular filtration rate (GFR) by more than 20-fold. Phenolic BaP metabolites also showed net secretion (1.5- to 3-fold). At times prior to 3 hr, BaP itself showed an average clearance of only 0.2 times the GFR. After 3 hr, BaP clearance increased to three times the GFR. Decreasing the dose of BaP injected also dramatically increased its clearance. Clearances of all four compounds studied were reduced by probenecid and other organic anion, including the herbicide 2,4-dichlorophenoxyacetic acid. HPLC analysis demonstrated that the bulk of the material excreted in the urine was not the parent compound, but sulfate or glucuronide conjugates of its phenolic or dihydrodiol metabolites. Excretion of sulfate conjugates predominated over the first 24 hr, whereas the glucuronide conjugates were the primary excretory products in succeeding days. In vitro, isolated renal tubules transported both glucuronide and sulfate conjugates, but sulfates were the preferred substrates. Isolated tubules were shown to be capable of catalyzing conjugation reactions, producing predominantly glucuronide conjugates. Liver slices produced both types of conjugates. Thus, the rapid excretion of BaP-7,8-dihydrodiol reflected a combination of two processes.(ABSTRACT TRUNCATED AT 250 WORDS)
Cytotoxic T lymphocyte antigen-4 (CTLA-4) gene polymorphisms and susceptibility to type 1 autoimmune hepatitis
Authors: Kosh Agarwal, Albert J. Czaja, David E. Jones, Peter T. Donaldson
Journal: Hepatology (2000)

Genetic susceptibility to type 1 autoimmune hepatitis is indicated by a preponderance of female subjects and strong associations with human leukocyte antigens (HLA) DRB1*0301 and DRB1*0401. The gene encoding cytotoxic T-lymphocyte antigen-4 (CTLA-4) on chromosome 2q33 may also influence autoimmunity. To determine the frequency and significance of the exon 1 adenine (A)-guanine (G) base-exchange polymorphism for CTLA-4 in patients with type 1 autoimmune hepatitis, 155 northern European Caucasoid patients and 102 ethnically-matched control subjects were tested by polymerase chain reaction. The genotype distribution was significantly different in patients compared to controls (AA = 50/155 patients vs. 51/102 controls; AG = 84/155 patients vs. 38/102 controls; GG = 21/155 patients vs. 13/102 controls, chi(2) = 8.94, P =.011). This difference was caused by a significant over-representation of the G allele in patients compared to controls (105/155 patients vs. 51/102 controls, chi(2) = 8.34, P =.004, odds ratio = 2.12). The GG genotype was associated with a significantly higher mean serum aspartate transaminase level (P =. 03), greater frequency of antibodies to thyroid microsomal antigens (P =.004) and was found more commonly in patients with HLA DRB1*0301 (P =.02). Treatment outcomes, however, were not affected by the genotype. The CTLA-4 G allele is more common in patients with type 1 autoimmune hepatitis and may represent a second susceptibility allele. Furthermore, there may be synergy between the HLA-DRB1*0301 and the GG genotype in terms of disease risk.
Ventricular Tachycardia Associated With Non-Freon Aerosol Propellants
Authors: R. D. Stewart
Journal: JAMA (1987)

<h3>To the Editor.—</h3> The case of a 2-year-old child who presented with seizures and ventricular tachycardia after exposure to the aerosol propellants isobutane,<i>n</i>-butane, and propane reported by Wason et al<sup>1</sup>poses a major question: was the exposure of the previously well child to these propellants sufficient to produce the respiratory arrest, coma, seizure activity, and episodes of ventricular tachycardia that recurred for more than four hours? The authors claim that "significant exposure" occurred because the three propellants were identified in a blood sample obtained two hours following the exposure. Regrettably, the authors failed to disclose the blood concentrations of the propellants, which prevents an accurate assessment of the amount absorbed. The authors also failed to report the weight of the aerosol can, which prevents estimation of the maximum amount expelled. Therefore, the magnitude of the exposure remains in serious doubt. The child's seizure activity began immediately following
Prognostic Modeling of Individual Patient Risk and Mortality Impact of Ischemic and Hemorrhagic Complications
Authors: Stuart J. Pocock, Roxana Mehran, Tim C. Clayton, Eugenia Nikolsky, Helen Parise, Martin Fahy, Alexandra J. Lansky, Michel E. Bertrand, A. Michael Lincoff, Jeffrey W. Moses, E. Magnus Ohman, Harvey D. White, Gregg W. Stone
Journal: Circulation (2009)

Background— Both ischemic and hemorrhagic complications increase mortality rate in acute coronary syndromes. Their frequency and relative importance vary according to individual patient risk profiles. We sought to develop prognostic models for the risk of myocardial infarction (MI) and major bleeding to assess their impact on risk of death and to examine the manner in which alternative antithrombotic regimens affect these risks in individual patients. Methods and Results— The Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial randomized 13 819 patients with acute coronary syndrome to heparin plus a glycoprotein IIb/IIIa inhibitor, bivalirudin plus a glycoprotein IIb/IIIa inhibitor, or bivalirudin alone. By logistic regression, there were 5 independent predictors of MI within 30 days (n=705; 5.1%) and 8 independent predictors of major bleeding (n=645; 4.7%), only 2 of which were common to both event types. In a covariate-adjusted, time-updated Cox regression model, both MI and major bleeding significantly affected subsequent mortality rate (hazard ratios, 2.7 and 2.9, respectively; both P &lt;0.001). Treatment with bivalirudin versus heparin plus a glycoprotein IIb/IIIa inhibitor was associated with a nonsignificant 8% increase in MI and a highly significant 50% decrease in major bleeding. Given the individual patient risk profiles and the fact that bivalirudin prevented ≈6 major bleeds for each MI that might occur from its use, the estimated reduction in bleeding was greater than the estimated increase in MI by bivalirudin alone rather than heparin plus a glycoprotein IIb/IIIa inhibitor for nearly all patients. Conclusions— Consideration of the individual patient risk profile for MI and major bleeding and the relative treatment effects of alternative pharmacotherapies permits personalized decision making to optimize therapy of patients with acute coronary syndrome. Clinical Trial Registration— clinicaltrials.gov Identifier: NCT00093158.
TREATMENT OF DIPHTHERIA.Read before the Wayne County Medical Society, 1894.
Authors: OSCAR S. ARMSTRONG
Journal: JAMA (1894)

There is no disease with which we have to contend that requires better surroundings or greater care in its treatment to insure a successful outcome, than diphtheria. It is rightly dreaded as one of the most deadly foes of childhood, and even adults do not escape its attacks. It is a treacherous disease, and one or two members of a family may have it in a mild form, while in the remaining children it may present its most malignant characteristics. Nor does its treacherous character end here, for often when our patient seems to be doing nicely, with membrane entirely gone, pulse and temperature normal and everything progressing favorably, some of its dangerous sequlÆ? make their appearance. The first record we have of diphtheria in America was the epidemic in Boston in the sixteenth century, since which time it has become completely domiciled. Originally the disease appeared in epidemic form
870-3 Metalloproteinase inhibition prevents diastolic stiffening, AMP-breakdown, and oxypurine accumulation in accelerated heart failure
Authors: Nazareno Paolocci, Barbara Tavazzi, Roberto Biondi, Yehezkiel A Gluzband, Mariangela Amorini, Carlo G Tocchetti, Sonia Donzelli, Michael T Crow, Giuseppe Lazzarino, David A Kass
Journal: Journal of the American College of Cardiology (2004)
Delayed Prescribing—A Sensible Approach to the Management of Acute Otitis Media
Authors: Paul Little
Journal: JAMA (2006)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Origin and Diversification of a Salamander Sex Pheromone System
Authors: Sunita Janssenswillen, Wim Vandebergh, Dag Treer, Bert Willaert, Margo Maex, Ines Van Bocxlaer, Franky Bossuyt
Journal: Molecular Biology and Evolution (2014)

Sex pheromones form an important facet of reproductive strategies in many organisms throughout the Animal Kingdom. One of the oldest known sex pheromones in vertebrates are proteins of the Sodefrin Precursor-like Factor (SPF) system, which already had a courtship function in early salamanders. The subsequent evolution of salamanders is characterized by a diversification in courtship and reproduction, but little is known on how the SPF pheromone system diversified in relation to changing courtship strategies. Here, we combined transcriptomic, genomic, and phylogenetic analyses to investigate the evolution of the SPF pheromone system in nine salamandrid species with distinct courtship displays. First, we show that SPF originated from vertebrate three-finger proteins and diversified through multiple gene duplications in salamanders, while remaining a single copy in frogs. Next, we demonstrate that tail-fanning newts have retained a high phylogenetic diversity of SPFs, whereas loss of tail-fanning has been associated with a reduced importance or loss of SPF expression in the cloacal region. Finally, we show that the attractant decapeptide sodefrin is cleaved from larger SPF precursors that originated by a 62 bp insertion and consequent frameshift in an ancestral Cynops lineage. This led to the birth of a new decapeptide that rapidly evolved a pheromone function independently from uncleaved proteins.
Modern Trends in Diseases of Coronary Arteries and Ischemic Heart Disease
Authors: Robert L. Grissom
Journal: JAMA (1964)

This is a hard cover publication of 16 articles that have already appeared in 1963, in<i>Progress in Cardiovascular Diseases.</i>A variety of experimental and clinical material is presented, but there is otherwise no effort to summarize the whole field. This "symposium" did not bring discussants together and no "off the cuff" remarks are included. Rather, it appears the editors sought out the individual authors and invited each one to prepare an article on a subject of his own choice. Each contribution has its own bibliography. There is no overall index but only a table of contents. Each of the authors is well known and has written authoritatively for the practicing physician who is already well grounded in cardiology. To those physicians who do not happen to be subscribers to the journal mentioned above, the present volume can be recommended as a compendium of articles on coronary heart disease.
IS THERE A GENDER DISPARITY IN RISK ASSOCIATION OF INFLAMMATORY BIOMARKERS WITH NEW ONSET DIABETES IN HEALTHY ADULT POPULATION?
Authors: Sandip K. Zalawadiya, Ashutosh Niraj, Vikas Veerana, Jyotiranjan Pradahan, Sidakpal Panaich, Jacob Sony, Luis Afonso
Journal: Journal of the American College of Cardiology (2010)
Gilles de la Tourette Syndrome Treated With Haloperidol
Authors: Elizabeth M. Craven
Journal: JAMA (1969)

<h3>To the Editor:</h3> The Gilles de la Tourette syndrome, although rare, continues to be a psychiatric disorder for which there is no clear-cut treatment. This syndrome is more common in boys between the ages of 5 and 15, and usually begins with eye blinking, followed by facial tics and grimaces. After a variable period of time, the tics spread to the neck, shoulders, trunk, and legs. The last symptom usually to develop, is coprolalia ( involuntary obscenity). In spite of comprehensive studies the etiology and precise treatment remain obscure.<sup>1,2</sup>Barsky reported diphenylhydantoin sodium (Dilantin) therapy.<sup>3</sup>In 1964, Lucas<sup>4</sup>reported treatment with phenothiazines, and in 1967, he cited therapy with haloperidol.<sup>5</sup>Shapiro used haloperidol, as well as placebo effect on this syndrome.<sup>6</sup>The majority of pediatric patients treated with haloperidol have required relatively small doses (2 to 6 mg per day) of medication, although Stevens reported a
Peak Flow Variability in the SAPALDIA Study and Its Validity in Screening for Asthma-related Conditions
Authors: NINO KÜNZLI, ELISABETH ZEMP STUTZ, ANDRE P. PERRUCHOUD, OTTO BRÄNDLI, JEAN-MARIE TSCHOPP, GIANFRANCO BOLOGNINI, WERNER KARRER, CHRISTIAN SCHINDLER, URSULA ACKERMANN-LIEBRICH, PHILIPPE LEUENBERGER
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

We used 3-wk peak expiratory flow (PEF) measurements (twice daily) made in the diary study of the population-based Swiss Study on Air Pollution and Lung Disease in Adults to describe PEF-variability (PEFvar) (amplitude as a percent of the mean, PEF [i.e., difference between morning and evening values divided by the mean]) in the study population and in five subgroups (physician-diagnosed asthma; current asthma, or physician-diagnosed asthma plus asthma attacks and/or medication; history of wheezing without a cold; hyperreactive; and nonsymptomatic). We assessed the performance of PEFvar as a potential tool with which to screen for asthma. Alternatively, subjects with a PEFvar of ⩾ 20%, ⩾ 30%, and ⩾ 50% on at least 2 d were considered to have high variability. The analyses were conducted for subgroups with different pretest probabilities for asthma-related conditions. The median PEFvar was 4.5%. Among asthmatic subjects, women had nonsignificantly higher PEFvar values than did men. In all other groups, women had significantly lower PEFvar. Both in the entire population and in subgroups with a higher pretest probability for asthma-related conditions, screening performance of PEF was limited. A PEFvar of ⩾ 20% on at least 2 d detected current asthma with a sensitivity of 36% (specificity = 90%; positive predictive value = 16.4%). Results were better among subjects with a history of wheezing without colds (sensitivity = 40.4%; specificity = 83.6%; positive predictive value = 45.2%). PEFvar, a useful measure both clinically and in epidemiology, is of limited value when unselected populations are screened for asthma-related conditions, since the overlap of PEFvar distributions across subgroups is large.
917 PROACTIVE BIRTH-COHORT AND RISK-BASED HEPATITIS C SCREENING: HEP C LINK TO CARE NYC
Authors: P.J. Gaglio, B.W. Petschow, R.S. Brown, I.M. Jacobson, D. Bernstein, M. Palmer, P.V. Perumalswami, D.T. Dieterich
Journal: Journal of Hepatology (2012)
Decreased NK cell frequency in chronic hepatitis C does not affectex vivo cytolytic killing
Authors: Chihiro Morishima, Denise M. Paschal, Chia C. Wang, Christina S. Yoshihara, Brent L. Wood, Anthony E. T. Yeo, Scott S. Emerson, Margaret C. Shuhart, David R. Gretch
Journal: Hepatology (2006)

Prior studies have suggested that natural killer (NK) cell function might be impaired in chronic hepatitis C virus (HCV) infection. Circulating NK cell frequency and cytolytic activity were examined freshly ex vivo in HCV-infected and uninfected subjects. Surprisingly, the intrinsic cytolytic activity of peripheral blood NK-enriched cells was similar between HCV-infected and uninfected groups ( P = .91). Although the percentage of circulating CD3−CD16/56+NK cells was 30% lower in HCV-infected compared with uninfected subjects ( P = .02) paralleled by a decrease of CD56dim cytolytic NK cells ( P = .02), overall K562 cytolysis by unfractionated peripheral blood mononuclear cells was not affected ( P = .29). Analysis of the relationships between NK cytolytic activity and other clinical information revealed an inverse association with liver fibrosis stage ( P = .035). In conclusion , NK cell cytolytic function does not appear to be impaired in chronic hepatitis C, but higher levels of NK cell cytolysis are associated with less liver fibrosis. (Hepatology 2006;43:573–580.)
Shedding of RANKL by Tumor-Associated MT1-MMP Activates Src-Dependent Prostate Cancer Cell Migration
Authors: Aaron L. Sabbota, Hyeong-Reh Choi Kim, Xiaoning Zhe, Rafael Fridman, R. Daniel Bonfil, Michael L. Cher
Journal: Cancer Research (2010)

Abstract Membrane type 1 matrix metalloproteinase (MT1-MMP) plays an essential role in protease-mediated extracellular matrix (ECM) degradation, but it also functions as a sheddase releasing non-ECM substrates such as receptor activator of NF-κB ligand (RANKL), an osteoclastogenic factor typically confined to the surface of osteoblasts. We previously found high expression of MT1-MMP in skeletal metastasis of prostate cancer patients, in a pattern similar to RANKL expression. We also showed that overexpression of MT1-MMP in prostate cancer cells increases tumor growth and osteolysis in an intratibial mouse model of bone metastasis, and that soluble factor(s) shed by tumor-derived MT1-MMP enhance osteoclast differentiation in a RANKL-dependent manner. Recent evidence indicates that the cognate receptor for RANKL, RANK, is expressed in prostate cancer cells, suggesting the presence of an autocrine pathway. In this study, we show that MT1-MMP–expressing LNCaP prostate cancer cells display enhanced migration. Moreover, conditioned medium from LNCaP cells expressing both RANKL and MT1-MMP stimulates the migration of MT1-MMP–deficient C42b prostate cancer cells. This enhanced chemotaxis can be abrogated by osteoprotegerin (soluble decoy receptor of RANKL), MIK-G2 (a selective inhibitor for MT1-MMP), and PP2 (a Src inhibitor). These findings indicate that tumor-derived MT1-MMP enhances tumor cell migration through initiation of an autocrine loop requiring ectodomain shedding of membrane-bound RANKL in prostate cancer cells, and that Src is a key downstream mediator of RANKL-induced migration of prostate cancer cells. Cancer Res; 70(13); 5558–66. ©2010 AACR.
Surgical Diseases of the Chest
Authors: OSLER A. Abbott
Journal: JAMA (1967)

<b>Foundations of Thoracic Surgery</b>, by F. Ronald Edwards, 180 pp, with illus, $10.25, Edinburgh and London: E. &amp; S. Livingstone, Ltd. (Baltimore: Williams &amp; Wilkins Co.), 1966. The second edition of Dr. Blades' excellent textbook on thoracic surgery is indeed welcome. It consists of multiple contributions from 20 separate authors, each of whom is a highly recognized authority in his field. The new edition not only brings matters up to date in each individual field but places particular emphasis on the recent developments in cardiovascular surgery. There is an entire new chapter describing the recent developments relative to coronary cineangiography and the surgical treatment of coronary heart disease. Detailed descriptions relative to operative procedures are given mainly for the newer operations not included in older textbooks. The whole field of thoracic surgery is well covered, and an excellent bibliography follows each chapter. The illustrations are highly informative, plentiful, and of
Inhaled Steroids and the Risk of Hospitalization for Asthma
Authors: James G. Donahue
Journal: JAMA (1997)

<h3>Objective.</h3> —To determine if anti-inflammatory treatment for asthma reduces the risk of asthma hospitalization. <h3>Design.</h3> —Retrospective cohort study. <h3>Setting.</h3> —A health maintenance organization (HMO) in eastern Massachusetts. <h3>Participants.</h3> —Members of the HMO who were identified during the period October 1991 through September 1994 as having a diagnosis of asthma using a computerized medical record system. <h3>Main Outcome.</h3> —Hospitalization for asthma. <h3>Results.</h3> —Of the 16 941 eligible persons, 742 (4.4%) were hospitalized for asthma. The overall relative risk (RR) of hospitalization among those who received inhaled steroids was 0.5 (95% confidence interval [CI], 0.4-0.6) after adjustment for β-agonist dispensing. Additional adjustment for age, race, other asthma medications, and amount and type of ambulatory care for asthma did not substantially affect the inverse relationship between use of inhaled steroids and hospitalization. Cromolyn was similarly associated with reduced risk, especially among children (RR,0.8;95%CI,0.7-0.9). In contrast, increasing β-agonist use was associated with increasing hospitalization risk even after adjustment for other factors and medications. The steroid-associated protection was most marked among individuals who received the largest amount of β-agonist. <h3>Conclusions.</h3> —Inhaled steroids and, to a lesser extent, cromolyn confer significant protection against exacerbations of asthma leading to hospitalization. These results support the use of inhaled steroids by individuals who require more than occasional β-agonist use to control asthma symptoms.
Expression of X protein and hepatitis B virus replication in chronic hepatitis
Authors: Yoshimichi Haruna, Norio Hayashi, Kazuhiro Katayama, Nobukabu Yuki, Akinori Kasahara, Yutaka Sasaki, Hideyuki Fusamoto, Takenobu Kamada
Journal: Hepatology (1991)

The X protein can act on the enhancer of hepatitis B virus in an in vitro system and elevate the transcriptional level of hepatitis B virus. However, because no relationship had been reported between X protein expression and hepatitis B virus replication in patients with chronic hepatitis B, we focused on its expression in the liver in comparison with markers of hepatitis B virus replication. Liver biopsy samples and sera from 59 carriers with HBsAg were examined immunohistochemically for X protein using rabbit IgG against recombinant X protein. There was a significant difference in the serum hepatitis B virus DNA level between X protein-positive and -negative patients (p less than 0.001). Serum pre-S1 and pre-S2 antigens were also measured quantitatively by enzyme immunoassay using monoclonal antibodies specific against each antigen. The titers of pre-S1 antigen in patients positive for X protein were significantly higher (p less than 0.001) than those of the X protein-negative patients (3.02 +/- 0.99 vs. 2.00 +/- 0.59, respectively). Similarly, the titers of pre-S2 antigen were 2.98 +/- 0.91 vs. 1.94 +/- 0.54, respectively (p less than 0.001). The rate of positivity of the X protein was higher (38 of 49; 77.6%) in the replicative group (serum HBeAg, serum hepatitis B virus DNA or HBcAg in liver positive) compared with that observed in the nonreplicative group (3 of 10; 30%--serum HBeAg, serum hepatitis B virus DNA and HBcAg in liver negative) (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)