tbuckley/cabot-search huggingface dataset:
Regulation of PKA Binding to AKAPs in the Heart
Authors: Daniel R. Zakhary, Christine S. Moravec, Meredith Bond
Journal: Circulation (2000)

Background —cAMP-dependent protein kinase (PKA) regulates a broad range of cellular responses in the cardiac myocyte. Downstream regulation of the PKA pathway is mediated by a class of scaffolding proteins called A-kinase anchoring proteins (AKAPs), which sequester PKA to specific subcellular locations through binding to its regulatory subunit (R). However, the effect of RII autophosphorylation on AKAP binding and the degree of RII autophosphorylation in failing and nonfailing human hearts remains unknown. Methods and Results —We investigated AKAP-RII binding by overlay analysis and surface plasmon resonance spectroscopy and measured RII autophosphorylation in human hearts by backphosphorylation. Binding of Ht31 peptide (representing the RII-binding region of AKAPs) to cardiac RII was increased ≈145% ( P &lt;0.01) for autophosphorylated RII relative to unphosphorylated control. By surface plasmon resonance, RII autophosphorylation significantly increased binding affinity to Ht31 by ≈200% ( P &lt;0.01). Baseline PKA-dependent phosphorylation of RII was significantly decreased ≈30% ( P &lt;0.05) in human hearts with dilated cardiomyopathy compared with nonfailing controls. Conclusions —These results suggest that AKAP binding of PKA in the heart is regulated by RII autophosphorylation. Therefore AKAP targeting of PKA may be reduced in patients with end-stage heart failure. This mechanism may be responsible for the decreased cAMP-dependent phosphorylation of proteins in dilated cardiomyopathy that we and others have previously observed.
Multicenter study evaluates `tight control' in diabetes
Authors: Terra Ziporyn
Journal: JAMA (1984)

Technological improvements in the past few years have made strict metabolic control a real possibility for patients with type I (insulin-dependent) diabetes. The question now is whether benefits of intensive insulin treatment through infusion pumps or multiple injections outweigh the considerable time, effort, and risks involved. The ongoing multicenter Diabetes Control and Complication Trial is trying to answer that question. Sponsored by the National Institutes of Health, the long-term study began in April 1983. Investigators are trying to determine whether maintaining the blood glucose level as close to normal as possible ("tight control") in a patient with diabetes will help prevent the often-progressive retinal and renal complications of diabetes. <h3>Testing an Assumption</h3> The crux of the problem lies in determining whether abnormal blood glucose levels are directly responsible for the complications. "The general assumption has always been that lower blood sugars prevent complications," says William Tamborlane, MD, associate professor of
A fast-acting elastase inhibitor in human monocytes.
Authors: E Remold-O'Donnell
Journal: The Journal of Experimental Medicine (1985)

A proteinase inhibitor active against neutrophil and pancreatic elastase was detected in extracts of cultured human monocytes and the human monocyte-like cell line U937. This component forms a covalent complex with the active site of elastase; the complex is stable in boiling sodium dodecyl sulfate solution, and is susceptible to nucleophilic cleavage. The activity of the elastase inhibitor is not detected in extracts of freshly isolated monocytes, but becomes detectable when the monocytes are allowed to mature in culture, with maximum levels occurring at 5-7 d. The monocyte inhibitor is fast-acting; its reaction with 125I-labeled elastase is complete in less than 1 min at 37 degrees C. Analysis by electrophoresis and studies using a heteroantiserum to alpha 1-proteinase inhibitor demonstrated that the elastase inhibitor of monocytes/U937 cells is not identical to alpha 1-proteinase inhibitor, the major elastase inhibitor of blood plasma. The extent of conversion of 125I-elastase to the 125I-elastase-inhibitor complex is proportional to the amount of U937 extract or cultured monocyte extract, indicating that this reaction can serve to quantify the elastase inhibitor. The elastase inhibitor is an abundant component in mature monocytes, with greater than or equal to 1.5 X 10(6) molecules/cell (greater than or equal to 12 micrograms per 10(8) cells, greater than 0.1% of total cell protein). Its mol wt is estimated at 50,000. Thus, the monocyte inhibitor should be classified as a putative regulator of neutrophil (and monocyte) elastase activity at inflammatory sites. This designation is based on the properties of the molecule, including its high concentration in maturing monocytes, its affinity for elastase, and its fast reaction with this enzyme.
Essential Athrombia: A Family Study
Authors: BARBARA A. GOLDMAN
Journal: Annals of Internal Medicine (1972)

This is the first report of a family with essential athrombia, a qualitative platelet disorder characterized by a moderate hemorrhagic diathesis. Diagnostic laboratory variables include a prolonged bleeding time, normal clot retraction, normal platelet factor 3 activity, and abnormalities in platelet aggregation. This disorder appears to be transmitted as a dominant trait, either autosomal or sex-linked.
A bidirectional crosstalk between iNKT cells and adipocytes mediated by leptin modulates susceptibility for T cell mediated hepatitis
Authors: Koen Venken, Sylvie Seeuws, Lennart Zabeau, Peggy Jacques, Tine Decruy, Julie Coudenys, Eveline Verheugen, Fien Windels, Dominiek Catteeuw, Michael Drennan, Serge Van Calenbergh, Bart N. Lambrecht, Akihiko Yoshimura, Jan Tavernier, Dirk Elewaut
Journal: Journal of Hepatology (2013)
A Multivalent Conjugate Vaccine for Prevention of Meningococcal Disease in Infants
Authors: Lee H. Harrison
Journal: JAMA (2008)

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
Delving into cornerstones of hypersensitivity to antineoplastic and biological agents: value of diagnostic tools prior to desensitization
Authors: E. Alvarez‐Cuesta, R. Madrigal‐Burgaleta, D. Angel‐Pereira, A. Ureña‐Tavera, M. Zamora‐Verduga, P. Lopez‐Gonzalez, M. P. Berges‐Gimeno
Journal: Allergy (2015)

Evidence regarding drug provocation test (DPT) with antineoplastic and biological agents is scarce. Our aim was to assess the usefulness of including DPT as a paramount gold standard diagnostic tool (prior to desensitization).Prospective, observational, longitudinal study with patients who, during a 3-year period, were referred to the Desensitization Program at Ramon y Cajal University Hospital. Patients underwent a structured diagnostic protocol by means of anamnesis, skin tests (ST), risk assessment, and DPT. Oxaliplatin-specific IgE was determined in oxaliplatin-reactive patients (who underwent DPT regardless of oxaliplatin-specific IgE results). Univariate analysis and multivariate analysis were used to identify predictors of the final diagnosis among several variables.A total of 186 patients were assessed. A total of 104 (56%) patients underwent DPT. Sixty-four percent of all DPTs were negative (i.e., hypersensitivity was excluded). Sensitivity for oxaliplatin-specific IgE (0.35 UI/l cutoff point) was 34%, specificity 90.3%, negative predictive value 45.9%, positive predictive value 85%, negative likelihood ratio 0.7, and positive likelihood ratio 3.5.These are the first reported data based on more than 100 DPTs with antineoplastic and biological agents (paclitaxel, oxaliplatin, rituximab, infliximab, irinotecan, and other drugs). Implementation of DPT in diagnostic protocols helps exclude hypersensitivity (in 36% of all referred patients), and avoids unnecessary desensitizations in nonhypersensitive patients (30-56% of patients, depending on culprit-drug). Drug provocation test is vital to validate diagnostic tools; consequently, quality data are shown on oxaliplatin-specific IgE and oxaliplatin-ST in the largest series of oxaliplatin-reactive patients reported to date (74 oxaliplatin-reactive patients). Identifying phenotypes and predictors of a diagnosis of hypersensitivity may be helpful for tailored plans.
Complications During Insertion of Narrow-Bore Feeding Tubes
Authors: Bruce K. Bohnker
Journal: JAMA (1985)

<h3>To the Editor.—</h3> I have read with interest the article by Hand et al<sup>1</sup>entitled "Inadvertent Transbronchial Insertion of Narrow-Bore Feeding Tube Into the Pleural Space." Several comments seem appropriate. Vaughan<sup>2</sup>reported a somewhat similar case on a patient after left hemiglossectomy and left radical neck dissection with tracheostomy. A fine-bore feeding tube was passed into and through the right main-stem bronchus and into the lung parenchyma. Before the chest radiograph was reviewed, 400 mL of a proprietary nutritive amino acid preparation (Clinifeed) was infused. The patient became hypotensive, cyanotic, tachycardic, and dyspneic, and the physical examination revealed bronchospasm. Emergency medical therapy was begun and the patient made an uneventful recovery. Several assertions made within the article are not supported by the stated reference. Concerning intracranial passage, Bauzarth<sup>3</sup>dealt with an 18-F nasogastric tube passed within a No. 34 Davol-Silastic nasopharyngeal airway. He recommended this to prevent
577 REAL-TIME PCR QUANTIFICATION OF SERUM AND INTRACELLULAR HBV DNA AND HDV RNA IN DIFFERENT SUBSETS OF CHRONIC HBV INFECTED PATIENTS
Authors: T. Pollicino, G. Raffa, G. Iannello, T. Santantonio, G.B. Gaeta, G. Squadrito, G. Colucci, C. Calvi, I. Cacciola, M. Levrero, G. Raimondo
Journal: Journal of Hepatology (2009)
Parvovirus B19 quiescence during the course of human immunodeficiency virus infection in persons with hemophilia
Authors: James J. Goedert, Dean D. Erdman, Barbara A. Konkle, Thomas J. Török, Michael M. Lederman, Dorothy Kleinert, Titica Mandalaki, Craig M. Kessler, Larry J. Anderson, Naomi L. C. Luban
Journal: American Journal of Hematology (1997)

To detect and characterize parvovirus B19 infection during the course of progressive immune deficiency from human immunodeficiency virus (HIV), ten subjects enrolled in the Multicenter Hemophilia Cohort Study were followed for 6.4 to 15 years from HIV seroconversion through extreme immune deficiency. Four to five sera or plasma samples from each subject, collected at predetermined CD4+ lymphocyte levels, were tested for immunoglobulin G (IgG) and M (IgM) B19 antibodies and DNA. All 42 samples were positive for B19 IgG antibodies, and three were weakly positive for IgM antibodies. Only one sample, collected coincident with HIV seroconversion, was unequivocally positive for B19 DNA. No persistent hematologic adverse effects of B19 infection were observed. Thus, although B19 IgG antibodies are highly prevalent among HIV-infected persons with hemophilia or related disorders, B19 viremia and its hematologic consequences were not detected, even with severe depletion of CD4+ lymphocytes. If primary B19 infection occurs after immune deficiency, however, the consequences may be more adverse. Am. J. Hematol. 56:248–251, 1997. © 1997 Wiley-Liss, Inc.
Automated SNP Genotype Clustering Algorithm to Improve Data Completeness in High-Throughput SNP Genotyping Datasets from Custom Arrays
Authors: Edward M. Smith, Jack Littrell, Michael Olivier
Journal: Genomics Proteomics & Bioinformatics (2007)

Abstract High-throughput SNP genotyping platforms use automated genotype calling algorithms to assign genotypes. While these algorithms work efficiently for individual platforms, they are not compatible with other platforms, and have individual biases that result in missed genotype calls. Here we present data on the use of a second complementary SNP genotype clustering algorithm. The algorithm was originally designed for individual fluorescent SNP genotyping assays, and has been optimized to permit the clustering of large datasets generated from custom-designed Affymetrix SNP panels. In an analysis of data from a 3 K array genotyped on 1,560 samples, the additional analysis increased the overall number of genotypes by over 45,000, significantly improving the completeness of the experimental data. This analysis suggests that the use of multiple genotype calling algorithms may be advisable in high-throughput SNP genotyping experiments. The software is written in Perl and is available from the corresponding author.
Dizygotic twin sisters with myelokathexis: Mechanism of its neutropenia
Authors: Shoichiro Taniuchi, Akemi Yamamoto, Toru Fujiwara, Masafumi Hasui, Shoji Tsuji, Yohnosuke Kobayashi
Journal: American Journal of Hematology (1999)

Dizygotic twin sisters were first found to have neutropenia at 1 year of age when evaluated for recurrent pulmonary infections. Since then they have remained neutropenic (0.05 approximately 0.5 x 10(9)/l). Despite of their neutropenia, myeloid hyperplasia was evident on a marrow smear examination, and a number of cells were hypersegmented with fine interlobular bridging with chromatin strands and cytoplasmic vacuolation. Electron microscopy showed apoptotic cells with condensed nuclei and apoptotic bodies in the cytoplasm. Although life span, hydrogen peroxide production, phagocytosis, spreading, and chemotaxis of peripheral neutrophils were normal, the survival of bone marrow neutrophils in both infants was markedly decreased when compared with that of normal bone marrow neutrophils. During the bone marrow culture apoptotic neutrophils were observed at an earlier stage in both patients than in normal controls, biochemically and morphologically. Morphology of bone marrow neutrophils in both patients resembled that of cultured control bone marrow neutrophils. Peripheral neutropenia and appearance of characteristic neutrophils in the bone marrow in myelokathexis are considered to be an expression of apoptosis of bone marrow neutrophils.
Bareback to basics: how gay porn undermines safe sex campaigns
Authors: R. Hurley
Journal: BMJ (2009)

In the early days of the HIV pandemic in the 1980s, chilling advertisements included a tombstone-like monolith emblazoned with the AIDS acronym, while John Hurt cautioned, “If you ignore AIDS it could be the death of you, so don’t die of ignorance” (www.nationalarchives.gov.uk/films/1979to2006/filmpage_aids.htm).

Such terrifying safe sex messages seem to have all but dried up, however. At the same time the depiction, indeed celebration, of unprotected anal intercourse in gay pornography has risen massively. The message this sends to young gay men that sex without condoms is OK is putting them at risk of HIV and other sexually transmitted infections.

The essence of today’s sexual health messages is that, because of advances in testing and treatment, people with HIV live normal and healthy lives. Of course, the reality isn’t so simple, and AIDS has no cure. …
Polycythemia Resulting from Abnormal Hemoglobins
Authors: D. J. Weatherall
Journal: New England Journal of Medicine (1969)

THE first step in the clinical assessment of patients with polycythemia is to decide whether the disease is part of a myeloproliferative syndrome, polycythemia vera, or due to one of the increasing list of disorders that result in a secondary erythrocytosis. One such condition is familial polycythemia.During the last two years it has been established that at least some familial polycythemias result from inherited hemoglobin variants. These observations are of particular interest since, in addition to increasing the diagnostic possibilities in patients with erythrocytosis, the structural analysis of the abnormal hemoglobins is providing important information about structure-function relations in . . .
Redifferentiation of Smooth Muscle Cells After Coronary Angioplasty Determined via Myosin Heavy Chain Expression
Authors: Masanori Aikawa, Yasunari Sakomura, Makiko Ueda, Kenjiro Kimura, Ichiro Manabe, Sugao Ishiwata, Nobuyuki Komiyama, Hiroshi Yamaguchi, Yoshio Yazaki, Ryozo Nagai
Journal: Circulation (1997)

Background The pathophysiology of phenotypic modulation of smooth muscle cells (SMCs) involved in restenosis after angioplasty is not well understood. Smooth muscle myosin heavy chain (SM MHC) isoforms (SM1 and SM2) are specific markers for SMC differentiation. In particular, SM2 is useful as a marker of mature SMCs. SMemb is a nonmuscle myosin heavy chain (NM MHC) whose expression is upregulated in immature or activated SMC. Methods and Results To determine SMC phenotypes in neointimal tissues after percutaneous transluminal coronary angioplasty (PTCA), we performed immunohistochemistry on human coronary arteries with antibodies against α-SM actin, SM1, SM2, and SMemb. Tissues were obtained from six autopsied patients and from atherectomy specimens from 16 patients who had undergone PTCA. Medial SMCs were positive for α-actin, SM1, and SM2. Expression of SM1 and SM2 in the neointima varied with the time after intervention, whereas α-actin was constitutively expressed in all cases studied. Neointimal cells at 16 and 20 days after PTCA contained α-actin but little or no SM1 or SM2, indicating that these cells modulated their phenotype to the immature state. Neointimal SMCs recovered SM MHC expression, first SM1 and then SM2, by 6 months after PTCA. Increased expression of SMemb was found in the neointima but without apparent relationship to the time after PTCA. Conclusions Neointimal SMCs show features of an undifferentiated state, indicated by altered expression of SM MHC, and undergo redifferentiation in a time-dependent manner. The expression of SM MHC isoforms provides insight into the biology of healing after angioplasty and furnishes useful tools for the understanding of the roles of differentiation and phenotypic modulation of SMCs in human vascular lesions.
Diabetes in the Pediatric Literature
Authors: Arlan L RosenBloom
Journal: Diabetes Care (1978)

Mini-Reviews will be a regular feature of DIABETES CARE. In the last issue, the first of these recurring reviews examined the literature on Psychosocial Issues in Diabetes. This issue the subject is Diabetes in the Pediatric Literature. The format of the Mini-Reviews is the presentation of abstracts of selected articles, with commentary on the topics raised by these articles. Dr. Arlan Rosenbloom will also be responsible for subsequent reviews of the pediatric literature. In order to provide a broad spectrum of commentary, the Editor will also ask other experts to comment on the articles. This month's guest commentator is Dr. Richard A. Guthrie.
Crystallographic analysis of a hydroxylated polychlorinated biphenyl (OH-PCB) bound to the catalytic estrogen binding site of human estrogen sulfotransferase.
Authors: Sergei Shevtsov, Evgeniy V Petrotchenko, Lars C Pedersen, Masahiko Negishi
Journal: Environmental Health Perspectives (2003)

Certain hydroxylated polychlorinated biphenyls (OH-PCBs) inhibit the human estrogen sulfotransferase (hEST) at subnanomolar concentrations, suggesting a possible pathway for PCB toxicity due to environmental exposure in humans. To address the structural basis of the inhibition, we have determined the crystal structure of hEST in the presence of the sulfuryl donor product 3 -phosphoadenosine 5 -phosphate and the OH-PCB 4,4 -OH 3,5,3,5 -tetraCB. The OH-PCB binds in the estrogen binding site with the position of the first phenolic ring in an orientation similar to the phenolic ring of 17 beta-estradiol. Interestingly, the OH-PCB does not bind in a planar conformation, but rather with a 30-degree twist between the phenyl rings. The crystal structure of hEST with the OH-PCB bound gives physical evidence that certain OH-PCBs can mimic binding of estrogenic compounds in biological systems.
Verapamil: Full spectrum calcium channel blocking agent: An overview
Authors: Juan R. Guerrero, Susan S. Martin
Journal: Medicinal Research Reviews (1984)

Oral verapamil approved for use in all forms of angina, with its additional heart rate-controlling properties has undergone extensive clinical investigation and use since its initial development and has been demonstrated to be safe, well-tolerated and effective over a broad range of cardiovascular disorders. Further potential therapeutic indications for verapamil use remain to be assessed. Additional research with this exciting drug is ongoing.
Mismatch Between lodine-123 and Xenon-133 SPECT rCBF Measurement
Authors: M STEINLING, A DESTEE
Journal: Clinical Nuclear Medicine (1986)

This report is concerned with the case of a man afflicted by multiple cerebral arteriovenous malformations. The rCBF measurement with Xe-133 inhalation was relatively elevated. However, I-123 iodoamphetamine imaging showed a relative reduction in radioactivity, and was a more accurate reflection of the clinical situation.
Can cardiac tamponade be diagnosed by echocardiography? Experimental studies.
Authors: J B Martins, R E Kerber
Journal: Circulation (1979)

The purpose of this study was to determine if respiratory variation and/or absolute size of echocardiographically measured right or left ventricular internal dimension at end-diastole (RVIDd or LIVIDd) are accurate indicators of the presence or severity of cardiac tamponade. We measured RVIDd or LVIDd by echocardiography in nine closed-chest, spontaneously breathing dogs in control and during hypotensive tamponade. With tamponade, the end-expiratory RVIDd and LVIDd were significantly smaller than control. Inspiratory increases in RVIDd and decreases in LVIDd were exaggerated during tamponade. Because of the wide range and overlap of RVIDd and LVIDd, no single expiratory value or amount of respiratory change indicated the presence or severity of tamponade. We conclude that if serial echocardiograms show a pericardial effusion, a decreasing end-expiratory RVIDd and LVIDd and an increasing percentage change in ventricular diameter with inspiration, a progressive degree of tamponade should be suspected However, a single echocardiogram cannot accurately predict the presence or severity of tamponade.
Abstract 2217: Impact of the ACUITY and TIMI Major Bleeding Definitions on One-Year Mortality in Patients with Acute Coronary Syndromes
Authors: Steven Manoukian, Frederick Feit, Michele D Voeltz, Ramin Ebrahimi, Martial Hamon, Derek P Chew, George D Dangas, Walter Desmet, A M Lincoff, Jeffrey W Moses, Charles Pollack, James W Hoekstra, Spencer B King, Harvey D White, E M Ohman, Roxana Mehran, Gregg W Stone
Journal: Circulation (2007)