tbuckley/cabot-search huggingface dataset:
Calcimimetics increase CaSR expression and reduce mineralization in vascular smooth muscle cells: mechanisms of action
Authors: Lucie Hénaut, Cédric Boudot, Ziad A. Massy, Irene Lopez-Fernandez, Sebastien Dupont, Aurélien Mary, Tilman B. Drüeke, Saïd Kamel, Michel Brazier, Romuald Mentaverri
Journal: Cardiovascular Research (2013)

Vascular calcification (VC) contributes to morbidity and mortality in patients with chronic kidney disease (CKD). Allosteric modulators of the calcium (Ca)-sensing receptor (CaSR) may slow the progression of VC in CKD patients either by reducing serum parathyroid hormone (PTH), Ca, and phosphate levels or by a direct effect on the vessel wall. The aim of this study was to examine the effects of calcimimetics on CaSR expression, cell phenotype, and mineral deposition in human vascular smooth muscle cells (h-VSMCs). Primary h-VSMCs were exposed for 14 days to increasing concentrations of Ca2+ (from 1.8 to 5 mmol/L) in the presence or absence of calcimimetics R-568 or AMG 641 (0.1 μmol/L). Mineralization was detected by Alizarin red staining, and the cell phenotype was assessed using immunocytochemistry and qRT–PCR. CaSR expression was evaluated using flow cytometry. Short- and long-term exposure (1 day to 14 days) of h-VSMCs to calcimimetics promoted CaSR protein transport from the endoplasmic reticulum to the plasma membrane with enhanced CaSR expression on the cell surface, together with an increase in total cell CaSR expression due to enhanced biosynthesis. In pro-mineralizing conditions, exposure to calcimimetics counteracted the Ca2+-dependent reduction of CaSR expression, decreased matrix collagen secretion, and mineral deposition by ∼90%. These effects involved CaSR activation since it could be inhibited by CaSR siRNA, but not scrambled siRNA. The calcimimetic-dependent increase in biosynthesis and activation of the CaSR in h-VSMCs probably play a key role in the protection against calcium-induced VC.
Synchronized Precordial Electroshock for Control of Cardiac Arrhythmias
Authors: Henry S. Miller
Journal: JAMA (1964)

Synchronized direct current precordial electroshock has been established as a safe method for the reversion of ectopic cardiac arrhythmias to normal and is successful in 90% of all patients. Three or more months after reversion 40% of the patients with marked left atrial hypertrophy or atrial fibrillation of more than two years' duration remained in normal sinus rhythm. However, all patients with atrial flutter and 80% of those with atrial fibrillation of less than six months, in whom left atrial enlargement was minimal to moderate, remained normal. The safety of the procedure under the proper circumstances justifies an attempt at the correction of ectopic cardiac arrhythmias in all patients who will benefit from normal sinus rhythm.
<i>C3orf58</i> , a Novel Paracrine Protein, Stimulates Cardiomyocyte Cell-Cycle Progression Through the PI3K–AKT–CDK7 Pathway
Authors: Farideh Beigi, Jeffrey Schmeckpeper, Pete Pow-anpongkul, James Alan Payne, Lunan Zhang, Zhiping Zhang, Jing Huang, Maria Mirotsou, Victor J. Dzau
Journal: Circulation Research (2013)

Rationale: The regenerative capacity of the heart is markedly diminished shortly after birth, coinciding with overall withdrawal of cardiomyocytes from cell cycle. Consequently, the adult mammalian heart has limited capacity to regenerate after injury. The discovery of factors that can induce cardiomyocyte proliferation is, therefore, of high interest and has been the focus of extensive investigation throughout the past years. Objective: We have recently identified C3orf58 as a novel hypoxia and Akt induced stem cell factor (HASF) secreted from mesenchymal stem cells, which can promote cardiac repair through cytoprotective mechanisms. Here, we tested the hypothesis that HASF can also contribute to cardiac regeneration by stimulating cardiomyocyte division and proliferation. Methods and Results: Neonatal ventricular cardiomyocytes were stimulated in culture for 7 days with purified recombinant HASF protein. Compared with control untreated cells, HASF-treated neonatal cardiomyocytes exhibited 60% increase in DNA synthesis as measured by bromodeoxyuridine incorporation. These results were confirmed by immunofluorescence confocal microscopy showing a 50% to 100% increase in the number of cardiomyocytes in the mitotic and cytokinesis phases. Importantly, in vivo cardiac overexpression of HASF in a transgenic mouse model resulted in enhanced level of DNA synthesis and cytokinesis in neonatal and adult cardiomyocytes. These proliferative effects were modulated by a phosphoinositide 3-kinase–protein kinase B–cycle-dependent kinase 7 pathway as revealed by the use of phosphoinositide 3-kinase -pathway–specific inhibitors and silencing of the Cdk7 gene. Conclusions: Our studies support the hypothesis that HASF induces cardiomyocyte proliferation via a phosphoinositide 3-kinase–protein kinase B–cycle-dependent kinase 7 pathway. The implications of this finding may be significant for cardiac regeneration biology and therapeutics.
Soft Tissue Uptake on Bone Scan in a Patient with Uremic Myopathy
Authors: DEAN J. SHANLEY, ARTHUR B. BUCKNER
Journal: Clinical Nuclear Medicine (1992)

Soft tissue activity demonstrated on bone scan may be the result of any process causing calcification or devitalization of the tissue. Conditions with a tendency to cause soft tissue calcification have been classified into three types: metastatic calcification, generalized calcinosis, and dystrophic calcification. Metastatic calcification is related to abnormal calcium or phosphorous metabolism resulting in calcification of normal tissue, and it can be seen with hyperparathyroidism, renal osteodystrophy, and sarcoidosis. Calcium deposition in the soft tissues, despite normal calcium metabolism, is referred to as calcinosis and is associated with the collagen vascular diseases and idiopathic tumoral calcinosis. Dystrophic calcification is caused by calcium deposition in abnormal or dead tissue and is seen with neoplastic, traumatic, and inflammatory processes. The authors present a case of extensive soft tissue activity visualized on bone scan in a patient with biopsy-proven uremic myopathy secondary to rheumatic nephritis and progressive renal failure.
Deficient flavoprotein component of the NADPH-dependent O2-.-generating oxidase in the neutrophils from three male patients with chronic granulomatous disease.
Authors: T G Gabig, B A Lefker
Journal: Journal of Clinical Investigation (1984)

The NADPH-dependent O2-.-generating oxidase in subcellular fractions from the neutrophils of three male patients with chronic granulomatous disease was compared with the corresponding preparations from normal neutrophils. The oxidase from normal neutrophils contained flavin adenine dinucleotide in an approximately 0.9:1 molar ratio with cytochrome b559. Each of the three chronic granulomatous disease patients had decreased amounts of the flavoprotein component of the oxidase fraction. The oxidase from two chronic granulomatous disease patients had undetectable amounts of cytochrome b559 whereas the third patient had a normal content of cytochrome b559, which was spectrally indistinguishable from the normal. The intrinsic cytochrome b559 in the oxidase fraction from stimulated neutrophils of the latter chronic granulomatous disease patient was not reduced by NADPH under anaerobic conditions, in distinction with the previously reported reduction of the normal cytochrome b559 under identical conditions. We conclude that the flavoprotein component of the oxidase may mediate transfer of electrons from NADPH to the cytochrome b559 in normal neutrophils, and that deficiency of this flavoprotein is associated with the chronic granulomatous disease phenotype in the three patients studied.
Effect of a Practice-Based Strategy on Test Ordering Performance of Primary Care Physicians
Authors: Wim H. J. M. Verstappen, Trudy van der Weijden, Jildou Sijbrandij, Ivo Smeele, Jan Hermsen, Jeremy Grimshaw, Richard P. T. M. Grol
Journal: JAMA (2003)

Numbers of diagnostic tests ordered by primary care physicians are growing and many of these tests seem to be unnecessary according to established, evidence-based guidelines. An innovative strategy that focused on clinical problems and associated tests was developed.To determine the effects of a multifaceted strategy aimed at improving the performance of primary care physicians' test ordering.Multicenter, randomized controlled trial with a balanced, incomplete block design and randomization at group level. Thirteen groups of primary care physicians underwent the strategy for 3 clinical problems (arm A; cardiovascular topics, upper and lower abdominal complaints), while 13 other groups underwent the strategy for 3 other clinical problems (arm B; chronic obstructive pulmonary disease and asthma, general complaints, degenerative joint complaints). Each arm acted as a control for the other.Primary care physician groups in 5 regions in the Netherlands with diagnostic centers recruited from May to September 1998.Twenty-six primary care physician groups, including 174 primary care physicians.During the 6 months of intervention, physicians discussed 3 consecutive, personal feedback reports in 3 small group meetings, related them to 3 evidence-based clinical guidelines, and made plans for change.According to existing national, evidence-based guidelines, a decrease in the total numbers of tests ordered per clinical problem, and of some defined inappropriate tests, is considered a quality improvement.For clinical problems allocated to arm A, the mean total number of requested tests per 6 months per physician was reduced from baseline to follow-up by 12% among physicians in the arm A intervention, but was unchanged in the arm B control, with a mean reduction of 67 more tests per physician per 6 months in arm A than in arm B (P =.01). For clinical problems allocated to arm B, the mean total number of requested tests per 6 months per physician was reduced from baseline to follow-up by 8% among physicians in the arm B intervention, and by 3% in the arm A control, with a mean reduction of 28 more tests per physician per 6 months in arm B than in arm A (P =.22). Physicians in arm A had a significant reduction in mean total number of inappropriate tests ordered for problems allocated to arm A, whereas the reduction in inappropriate test ordered physicians in arm B for problems allocated to arm B was not statistically significant.In this study, a practice-based, multifaceted strategy using guidelines, feedback, and social interaction resulted in modest improvements in test ordering by primary care physicians.
Prosthetic Valve Endocarditis Caused by Legionella pneumophila
Authors: ROBERT E. McCABE
Journal: Annals of Internal Medicine (1984)

Prosthetic valve endocarditis due to Legionella pneumophila occurred in a woman who had aortic and mitral valve replacements with porcine xenografts. During surgery for persistent fever and aortic regurgitation due to presumed endocarditis, she had vegetations involving both the aortic and mitral valve prostheses with a circumferential abscess of the aortic annulus. Cultures, Dieterle stain, and direct fluorescent antibody stain of valve tissue, and subsequent measurements of serum antibody levels confirmed L. pneumophila as the infecting organism. This infection occurred in the absence of pneumonia. Legionella pneumophila must be considered a potential cause of culture-negative prosthetic valve endocarditis and should be sought in appropriate clinical circumstances.
Ectopic Gonadotropin Production before Clinical Recognition of Bronchogenic Carcinoma
Authors: Saul W. Rosen, Charles E. Becker, Sheldon Schlaff, John Easton, Morton C. Gluck
Journal: New England Journal of Medicine (1968)

GONADOTROPIN production by lung tumors has previously been found in men with well advanced carcinoma of the bronchus.1 , 2 In the following case the plasma had an increased concentration of gonadotropin when roentgenograms of the chest, bronchoscopic examination and scalene lymph nodes gave no evidence of tumor more than one year before the clinical diagnosis was ultimately established.Case ReportWhile taking isoniazid and para-aminosalicylic acid for pulmonary tuberculosis of the right upper lobe, a 70-year-old cigarette smoker (VAH 227–12–9910, NIH 072262) noticed bilateral gynecomastia. Physical examination was otherwise unremarkable, including symmetrical testes without palpable tumor. The protein-bound iodine, plasma cortisol . . .
Naratriptan mitigates CGRP1-associated motor neuron degeneration caused by an expanded polyglutamine repeat tract
Authors: Makoto Minamiyama, Masahisa Katsuno, Hiroaki Adachi, Hideki Doi, Naohide Kondo, Madoka Iida, Shinsuke Ishigaki, Yusuke Fujioka, Shinjiro Matsumoto, Yu Miyazaki, Fumiaki Tanaka, Hiroki Kurihara, Gen Sobue
Journal: Nature Medicine (2012)
Calcitriol for Postmenopausal Osteoporosis
Authors: A.M. Parfitt
Journal: Annals of Internal Medicine (1990)

Letters and Corrections15 January 1990Calcitriol for Postmenopausal OsteoporosisA.M. Parfitt, MB, BChirA.M. Parfitt, MB, BChirSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-112-2-147_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor:Gallagher and Riggs (1) recently criticized the report by Ott and Chesnut (2) on calcitriol treatment in postmenopausal osteoporosis. They referred to their own placebo-controlled study (3), which found that "3 years of treatment with calcitriol of women with postmenopausal osteoporosis resulted in a highly significant 65% reduction of vertebral fracture rate." They failed to mention that the placebo was given for only 1 year, so that the fracture rates in the second and third years of calcitriol treatment were compared with historical, not with concurrent, controls. In another study (4) cited by Gallagher and...References1. GallagherRiggs JB. Calcitriol for postmenopausal osteoporosis. Ann Intern Med. 1989;111:621. LinkGoogle Scholar2. OttChesnut SC. Calcitriol treatment is not effective in post-menopausal osteoporosis. Ann Intern Med. 1989;110:267-74. LinkGoogle Scholar3. GallagherRiggsReckerGoldgar JBRD. The effect of calcitriol on patients with postmenopausal osteoporosis with special reference to fracture frequency. Proc Soc Exp Biol Med. 1989;191:287-92. CrossrefMedlineGoogle Scholar4. AloiaVaswaniYehEllisYasumuraCohn JAJKSS. Calcitriol in the treatment of postmenopausal osteoporosis. Am J Med. 1988;84:401-8. CrossrefMedlineGoogle Scholar5. Parfitt A. Use of calciferol and its metabolites and analogs in osteoporosis; current status. Drugs. 1988;36:513-20. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Henry Ford Hospital Detroit, MI 48202 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 January 1990Volume 112, Issue 2Page: 147-147KeywordsCalcitriolOsteoporosis Issue Published: 15 January 1990 PDF DownloadLoading ...
Human Dissection and Experimentation With Drugs
Authors: Harry F. Dowling
Journal: JAMA (1967)

Roger Bacon<sup>1</sup>in the 13th century stated the dilemma of the physician-investigator thus: The operative and practical sciences which do their work on insensate bodies can multiply their experiments till they get rid of deficiency and errors, but a physician cannot do this because of the nobility of the material in which he works. Confronted with this dilemma, some investigators substituted speculation for experimentation, others sought answers from the lower animals, and a few used humans as subjects. How well were the rights of these humans respected? In Walter Reed's experiments, in the early studies of the therapeutic value of penicillin, streptomycin, and poliomyelitis vaccine, and in hundreds of others, investigators were scrupulous in consulting each person before the experiment was performed. But examples illustrating a contrary attitude can be found. In 1836, a New Orleans physician wrote with regard to the shock-like state in cholera: I have been
Hyperbaric Oxygen Therapy: Size of Infarct Determines Therapeutic Efficacy
Authors: STANLEY C. GLAUSER
Journal: Annals of Internal Medicine (1973)

There are differing reports of the efficiency of hyperbaric oxygen therapy for thrombotic and embolic states. An analysis of the volume of tissue necrotized as a function of the radius of tissue originally supplied with oxygen by the occluded vessel was made. The volume of necrosis increases rapidly as the cube of the original radius. The volume of tissue saved by breathing 100% oxygen at three atmospheres increases more slowly, as the square of the original radius. Thus the percent of tissue saved varies according to the reciprocal of the original radius, and any phenomena that produce multiple small necrotic areas will respond more favorably to hyperbaric oxygen therapy than any phenomena that produce one large volume of necrosis.
Monoclonal T Cells Identified in Early NOD Islet Infiltrates
Authors: Yang Yang, Brett Charlton, Akira Shimada, Richard Dal Canto, C.Garrison Fathman
Journal: Immunity (1996)

To examine the hypothesis that a single initiating antigen was recognized by a monoclonal T cell population leading to subsequent inflammatory insulitis in nonobese (NOD) mouse islets, we examined the T cell receptor (TCR) Vβ repertoire of islet-infiltrating T cells in very young (2-week-old) NOD mice. In independent experiments, we repeatedly identified one monoclonal TCR Vβ8.2 gene product expressed by T lymphocytes infiltrating the islets of NOD mice at 2 weeks of age. The resultant inflammatory response quickly obscures the monoclonal nature of the initiating event. These data suggest that autoimmune diabetes in NOD mice may be initiated by recognition of a single autoantigen.
Abstract 2117: Lasonolide A-induced premature chromosome condensation is mediated by the proto-oncogene c-Raf (Raf1).
Authors: Yong-Wei Zhang, Rozenn Josse, Arun Ghosh, Ji Luo, Yves Pommier
Journal: Cancer Research (2013)

Abstract Lasonolide A (LSA) was originally identified in a screen for novel antitumor compounds from marine organisms with high and selective cytotoxicity against mesenchymal cancer cells. We recently demonstrated that LSA induces rapid and reversible premature chromosome condensation (PCC) associated with profound epigenetic alterations in different cell types, independently of cyclin-dependent kinases activation. In order to identify cellular targets involved in LSA sensitivity, we used a pool of kinases and phosphatases shRNAs in the human colon carcinoma HCT-116 cell line. Among the genes whose inactivation promotes the survival of LSA-treated cells, we observed an enrichment of genes involved in mitotic functions including Raf1, a well-known serine-threonine kinase regulating cell proliferation and survival. LSA induces the rapid and reversible phosphorylation of Raf1 on Ser338 in a time- and a dose-dependent manner. To establish a causal relationship between LSA-induced PCC and Raf1, we first used siRNA targeting Raf1. Knocking-down Raf1 decreased LSA-induced PCC. Furthermore, mouse embryonic fibroblasts depleted in Raf1 were found resistant to LSA-induced PCC. Our results suggest a novel role of Raf1 in chromatin condensation. They also demonstrate that the target of LSA affects the c-Raf pathway and a novel mechanism of action of LSA as an effective inducer of PCC and potential novel anticancer agent. Citation Format: Yong-Wei Zhang, Rozenn Josse, Arun Ghosh, Ji Luo, Yves Pommier. Lasonolide A-induced premature chromosome condensation is mediated by the proto-oncogene c-Raf (Raf1). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2117. doi:10.1158/1538-7445.AM2013-2117 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
COMPARISON OF EVEROLIMUS–ELUTING STENTS WITH SIROLIMUS–ELUTING STENTS: INTIMAL HYPERPLASIA AND VASCULAR CHANGES ASSESSED BY VOLUMETRIC INTRAVASCULAR ULTRASOUND ANALYSIS
Authors: Seung–Whan Lee, Seung Mo Kang, Young–Rak Cho, Gyung–Min Park, Jung–Min Ahn, Jong–Young Lee, Won–Jang Kim, Soo–Jin Kang, Duk–Woo Park, Young–Hak Kim, Cheol Whan Lee, Seong–Wook Park, Seung–Jung Park
Journal: Journal of the American College of Cardiology (2013)
688 IL6 POLYMORPHISMS PLAY A ROLE IN INFLUENCING THE HISTOLOGICAL PROGRESSION IN PATIENTS WITH CHRONIC HCV INFECTION AND NORMAL TRANSAMINASES
Authors: E. Fornasiere, C. Vandelli, E. Falleti, C. Colletta, E. Fontanini, S. Camet, A. Cussigh, D. Bitetto, C. Smirne, R. Minisini, C. Fabris, P. Toniutto, M. Pirisi
Journal: Journal of Hepatology (2010)
Comparison of combination therapy with single-drug therapy in early rheumatoid arthritis: a randomised trial
Authors: Timo Möttönen, Pekka Hannonen, Marjatta Leirisalo-Repo, Martti Nissilä, Hannu Kautiainen, Markku Korpela, Leena Laasonen, Heikki Julkunen, Reijo Luukkainen, Kaisa Vuori, Leena Paimela, Harri Blåfield, Markku Hakala, Kirsti Ilva, Urpo Yli-Kerttula, Kari Puolakka, Pentti Järvinen, Mikko Hakola, Heikki Piirainen, Jari Ahonen, Ilppo Pälvimäki, Sinikka Forsberg, Kalevi Koota, Claes Friman
Journal: The Lancet (1999)
RNA editing: a novel mechanism for regulating lipid transport from the intestine.
Authors: J Scott, S C Wallis, M S Davies, J K Wynne, L M Powell, D M Driscoll
Journal: Gut (1989)

Human apolipoprotein (apo)-B mRNA undergoes a novel tissue specific editing reaction which replaces a genomically templated cytidine with uridine. This substitution converts codon 2153 from glutamine (CAA) in apo-B100 mRNA to a stop codon (UAA) in apo-B48 mRNA. This novel RNA editing process is responsible for the generation of hepatic apo-B100 and intestinal apo-B48. We have established the following concerning this process: (1) by transfection of a series of deletion mutants into the rat hepatoma cell line McArdle 7777, which makes both apo-B100 and apo-B48, we have defined a minimum sequence of 26 nucleotides that is required for apo-B mRNA editing. The sequence containing the modified nucleotide forms a 26 nucleotide highly conserved stem loop with the modified nucleotide occurring in an 8-base loop. (2) Conversion in vitro of apo-B mRNA has been established, using cell free S100 cytoplasmic extract and synthetic RNA templates. Activity was abolished by protease treatment. (3) Transgenic mice were created which expressed a human apo-B construct spanning the stop codon. Apo-B mRNA was found in all tissues examined and this was shown to undergo editing. (4) In the rat liver, which produces apo B-100 and apo-B48, modulation of the relative proportion of these proteins by thyroxine was demonstrated to be mediated at the level of the RNA editing mechanism. It is concluded that apo-B mRNA is edited by a generally expressed protein and editing is highly regulated.
Leukemia Mortality in Infancy
Authors: David Hewitt
Journal: New England Journal of Medicine (1964)

OFFICIAL statistics relating to the white population of the United States1 suggest that a substantial decline in the leukemia mortality of infants (up to eleven months of age) began in the early 1940's and persisted until about 1955.2 , 3 A more recent decline of mortality has also been reported, on the basis of very small numbers, from Norway.4 In England and Wales, on the other hand, the statistics5 indicate little or no change (Table 1). Hence the rate for white infants in the United States, which in the 1940's was some 60 per cent greater than that for English infants (and . . .