tbuckley/cabot-search huggingface dataset:
The effects of diadenosine polyphosphates on the cardiovascular system
Authors: N Flores
Journal: Cardiovascular Research (1999)

Diadenosine polyphosphates are members of a group of dinucleoside polyphosphates that are ubiquitous, naturally occurring molecules. They form a recently identified class of compounds derived from ATP and consist of two adenosine molecules bridged by up to six phosphate groups. These compounds are stored in high concentrations in platelet dense granules and are released when platelets become activated. Some of the compounds promote platelet aggregation, while others are inhibitory. Possible roles as neurotransmitters, extracellular signalling molecules or 'alarmones' secreted by cells in response to physiologically stressful stimuli have been postulated. Recent studies suggest a role for these compounds in atrial and synaptic neurotransmission. Studies using isolated mesenteric arteries indicate an important role of phosphate chain length in determining whether diadenosine polyphosphates produce vasodilatation or vasoconstriction, but in the coronary circulation, diadenosine polyphosphates generally produce vasodilatation via mechanisms thought to involve release of NO or prostacyclin (PGI2). They produce cardiac electrophysiological effects by altering ventricular refractoriness at submicromolar concentrations and reduce heart rate. Mechanisms involving KATP channels have been proposed in addition to the involvement of P1- and P2-purinergic receptors and the specific diadenosine polyphosphate receptor identified on isolated cardiac myocytes. Clinical evidence suggests a role for diadenosine polyphosphates in hypertensive patients and those with the Chédiak–Higashi syndrome. This review outlines the effects of these compounds on the cardiovascular system and considers their potential involvement in mediating the pathophysiological effects associated with platelet activation during myocardial ischaemia.
Kringle-containing fragments of apolipoprotein(a) circulate in human plasma and are excreted into the urine.
Authors: V Mooser, S M Marcovina, A L White, H H Hobbs
Journal: Journal of Clinical Investigation (1996)

Apolipoprotein(a) [apo(a)] contains multiple kringle 4 repeats and circulates as part of lipoprotein(a) [Lp(a)]. Apo(a) is synthesized by the liver but its clearance mechanism is unknown. Previously, we showed that kringle 4-containing fragments of apo(a) are present in human urine. To probe their origin, human plasma was examined and a series of apo(a) immunoreactive peptides larger in size than urinary fragments was identified. The concentration of apo(a) fragments in plasma was directly related to the plasma level of Lp(a) and the 24-h urinary excretion of apo(a). Individuals with low (< 2 mg/dl) plasma levels of Lp(a) had proportionally more apo(a) circulating as fragments in their plasma. Similar apo(a) fragments were identified in baboon plasma but not in conditioned media from primary cultures of baboon hepatocytes, suggesting that the apo(a) fragments are generated from circulating apo(a) or Lp(a). When apo(a) fragments purified from human plasma were injected intravenously into mice, a species that does not produce apo(a), apo(a) fragments similar to those found in human urine were readily detected in mouse urine. Thus, we propose that apo(a) fragments in human plasma are derived from circulating apo(a)/Lp(a) and are the source of urinary apo(a).
Commentary on JFK autopsy articles
Authors: C. A. Crenshaw
Journal: JAMA (1995)

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
The role of non-ras transforming genes in chemical carcinogenesis.
Authors: C S Cooper
Journal: Environmental Health Perspectives (1991)

DNA transfection experiments using the NIH 3T3 mouse fibroblast cell line have demonstrated that chemically induced tumors and chemically transformed cell lines frequently contain dominant transforming genes. Although many of the genes detected using the NIH 3T3 transfection-transformation assay are activated versions of H-ras, K-ras, and N-ras, in some experimental systems activated forms of genes such as met and neu that are unrelated to ras have been observed. The activated met gene was originally detected in a human cell line that had been transformed by exposure to N-methyl-N'-nitro-N-nitrosoguanidine. Subsequent studies demonstrated that the met proto-oncogene encodes a novel growth factor receptor and that gene activation involves the production of a chimeric gene in which the regions of met encoding the extracellular and transmembrane domains of the receptor are replaced by the 5'-region of an unrelated gene called trp. The activated neu gene was detected in tumors of the nervous system that arose in mice following transplacental exposure to N-ethyl-N-nitrosourea. The neu gene also encodes a novel growth factor receptor but, in contrast to met, its activation involves a single T:A----A:T point mutation in the region of the neu gene encoding the receptor transmembrane domain. The presence of genetic alterations in chemically induced malignancies has also been assessed in cytogenetic studies and by Southern analysis of DNA from neoplastic cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Antiangiogenic treatment with Sunitinib ameliorates inflammatory infiltrate, fibrosis, and portal pressure in cirrhotic rats
Authors: Sònia Tugues, Guillermo Fernandez-Varo, Javier Muñoz-Luque, Josefa Ros, Vicente Arroyo, Juan Rodés, Scott L. Friedman, Peter Carmeliet, Wladimiro Jiménez, Manuel Morales-Ruiz
Journal: Hepatology (2007)

Liver cirrhosis is a very complex disease in which several pathological processes such as inflammation, fibrosis, and pathological angiogenesis are closely integrated. We hypothesized that treatment with pharmacological agents with multiple mechanisms of action will produce superior results to those achieved by only targeting individual mechanisms. This study thus evaluates the therapeutic use of the multitargeted receptor tyrosine kinase inhibitor Sunitinib (SU11248). The in vitro effects of SU11248 were evaluated in the human hepatic stellate cell line LX-2 by measuring cell viability. The in vivo effects of SU11248 treatment were monitored in the livers of cirrhotic rats by measuring angiogenesis, inflammatory infiltrate, fibrosis, α-smooth muscle actin (α-SMA) accumulation, differential gene expression by microarrays, and portal pressure. Cirrhosis progression was associated with a significant enhancement of vascular density and expression of vascular endothelial growth factor-A, angiopoietin-1, angiopoietin-2, and placental growth factor in cirrhotic livers. The newly formed hepatic vasculature expressed vascular cellular adhesion molecule 1 and intercellular adhesion molecule 1. Interestingly, the expression of these adhesion molecules was adjacent to areas of local inflammatory infiltration. SU11248 treatment resulted in a significant decrease in hepatic vascular density, inflammatory infiltrate, α-SMA abundance, LX-2 viability, collagen expression, and portal pressure. Conclusion: These results suggest that multitargeted therapies against angiogenesis, inflammation, and fibrosis merit consideration in the treatment of cirrhosis. (Hepatology 2007.)
Femur fracture in an infant
Authors: J. S Radesky, N. F Sugar
Journal: BMJ (2009)

A 4 month old baby was brought to the emergency department because he was not moving his left leg. The parents reported that the baby twisted and fell when his father was changing his nappy. The father caught the baby by his leg before he hit the floor. The parents noted something was wrong immediately and brought the baby in for care. The baby had been born at full term after an uncomplicated pregnancy and delivery and had normal growth and development. The baby’s parents were married and both employed, and he was their first child. Radiography showed an acute oblique mid-shaft fracture of the left femur. The baby was clearly in pain when he moved, but his leg did not seem to be swollen. The remainder of the examination was normal. ### Short answers
A perspective on the potential development of environmentally acceptable light-duty diesel vehicles.
Authors: R Hammerle, D Schuetzle, W Adams
Journal: Environmental Health Perspectives (1994)

Between 1979 and 1985, an international technical focus was placed upon potential human health effects associated with exposure to diesel emissions. A substantial data base was developed on the composition of diesel emissions; the fate of these emissions in the atmosphere; and the effects of whole particles and their chemical constituents on microorganisms, cells, and animals. Since that time, a number of significant developments have been made in diesel engine technology that require a new look at the future acceptability of introducing significant numbers of light-duty diesel automobiles into the European and American markets. Significant engineering improvements have been made in engine design, catalysts, and traps. As a result, particle emissions and particle associated organic emissions have been reduced by about 10 and 30 times, respectively, during the past 10 years. Research studies to help assess the environmental acceptability of these fuel-efficient engines include the development of an emissions data base for current and advanced diesel engines, the effect of diesel emissions on urban ozone formation and atmospheric particle concentrations, the effect of fuel composition, e.g., lower sulfur and additives on emissions, animal inhalation toxicology studies, and fundamental molecular biology studies.
Hypercalcemia and Complete Heart Block
Authors: HENRY GINSBERG
Journal: Annals of Internal Medicine (1973)

Letters1 December 1973Hypercalcemia and Complete Heart BlockHENRY GINSBERG, M.D., KENNETH V. SCHWARTZ, M.D.HENRY GINSBERG, M.D., KENNETH V. SCHWARTZ, M.D.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-79-6-903_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The presence of complete atrioventricular (A-V) block in an acutely ill patient is most often associated with an acute myocardial infarction. Less common causes are bacterial endocarditis, inflammatory lesions of the conduction system, and thyrotoxicosis. We report a case in which hypercalcemia secondary to the milk-alkali syndrome (1, 2) seemed to be the cause of complete A-V block. Although first-degree heart block has been reported in association with hypercalcemia (3), we believe that this is the first reported case in which second- and third-degree A-V block developed secondary to hypercalcemia.A 38-year-old man presented with a 2-day...References1. MCMILLAN D and FREEMAN R: Milk-alkali syndrome: a study of the acute disorder with comments on the development of the chronic condition. Medicine (Baltimore) 44:485-501, 1965 CrossrefMedlineGoogle Scholar2. PUNSAR S and SOME T: The milk-alkali syndrome. Acta Med Scand 173:435-449, 1963 CrossrefMedlineGoogle Scholar3. BRONSKY D, DUBIN A, and WALDSTEIN S: Calcium and the electrocardiogram. II. the electrocardiographic manifestations of hyperparathyroidism and of marked hypercalcemia from various other etiologies. Am J Cardiol 7:833-839, 1961 CrossrefGoogle Scholar4. HOFF H, SMITH P, and WINKLER A: Electrocardiographic changes and concentration of calcium in serum following injection of calcium chloride. Am J Physiol 125:162-171, 1939 CrossrefGoogle Scholar5. CLARKE H: The action of calcium on the human electrocardiogram. Am Heart J 22:367-373, 1941 CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: HENRY GINSBERG, M.D.; KENNETH V. SCHWARTZ, M.D.Affiliations: Boston University Medical Services Boston City Hospital Boston, Massachusetts PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byComplete heart block associated with paraneoplastic hypercalcemia: a case reportReversible complete heart block due to hypercalcaemiaEnvironmental Toxins and the HeartCardiac conduction in patients with hypercalcaemia due to primary hyperparathyroidismExtranodal renal non-Hodgkin's lymphoma and severe hypercalcaemiaPractical aspects of advanced paediatric cardiopulmonary resuscitationEnhancement by Ca2+ ions of cholinergic effects on the canine heart in situTreatment of HypercalcemiaCase 40-1974 1 December 1973Volume 79, Issue 6Page: 903-903KeywordsAcute myocardial infarctionEndocarditisHeartHypercalcemiaLesions ePublished: 1 December 2008 Issue Published: 1 December 1973 PDF downloadLoading ...
Impaired Endothelial Function and Increased Carotid Stiffness in 9-Year-Old Children With Low Birthweight
Authors: Helena Martin, Jie Hu, Gerhard Gennser, Mikael Norman
Journal: Circulation (2000)

Background —Low birthweight (LBW) has been associated with an increased incidence of adult cardiovascular disease. Endothelial dysfunction and loss of arterial elasticity are early markers of hypertension and atherosclerosis. We studied the prevalence of these markers in 44 healthy, prepubertal (age 9±1.3 years) children, 22 with LBW for age. Methods and Results —Endothelial function in skin was tested with the local application of acetylcholine (inducing endothelium-dependent vasodilation) and nitroglycerin (endothelium-independent vasodilation), and local perfusion changes were measured with the laser Doppler method. The elastic properties of the abdominal aorta and common carotid artery were measured with an ultrasonic vessel-wall tracking system. Endothelium-dependent vasodilation was lower in children with LBW (88±33 perfusion units [PU]) than in normal-birthweight controls (133±34 PU, P &lt;0.001). There was no difference in aortic or carotid elasticity between the 2 groups, but a negative correlation was found between birthweight and stiffness of the carotid artery wall ( r =−0.45, P &lt;0.01). Endothelium-independent vasodilation and blood pressure were similar in the 2 groups. Conclusions —Schoolchildren with a history of LBW show impaired endothelial function and a trend toward increased carotid stiffness. These findings may be early expressions of vascular compromise, contributing to susceptibility to disease in adult life.
Industrial lab-on-a-chip: Design, applications and scale-up for drug discovery and delivery
Authors: Goran T. Vladisavljević, Nauman Khalid, Marcos A. Neves, Takashi Kuroiwa, Mitsutoshi Nakajima, Kunihiko Uemura, Sosaku Ichikawa, Isao Kobayashi
Journal: Advanced Drug Delivery Reviews (2013)
Chronic 1,25-dihydroxyvitamin D3 administration in the rat reduces the serum concentration of 25-hydroxyvitamin D by increasing metabolic clearance rate.
Authors: B P Halloran, D D Bikle, M J Levens, M E Castro, R K Globus, E Holton
Journal: Journal of Clinical Investigation (1986)

Administration of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] can lower the serum concentration of 25-hydroxyvitamin (25-OH-D). To determine if 1,25(OH)2D3 lowers serum 25-OH-D by increasing clearance or reducing production, we directly measured the metabolic clearance rate (MCR) of 25-OH-D in rats chronically infused with 1,25(OH)2D3. Chronic 1,25(OH)2D3 administration (0 to 75 pmol/d) reduced, in a time- and dose-dependent fashion, the serum concentrations of 25-OH-D3 and 24,25(OH)2D3 from 18 +/- 2 to 9 +/- 1 ng/ml and from 4.8 +/- 0.7 to 1.3 +/- 0.3 ng/ml, respectively, and increased sevenfold the in vitro conversion of 25-OH-D to 24,25(OH)2D3 by kidney homogenates. The reduction in serum 25-OH-D3 was completely accounted for by an increase in MCR. No change in production occurred. The influence of 1,25(OH)2D3 on serum 25-OH-D3 and 24,25(OH)2D3 was shown not to be dependent on induction of hypercalcemia. These data suggest that chronic 1,25(OH)2D3 administration lowers serum 25-OH-D by increasing the metabolic clearance of 25-OH-D3 and not by decreasing its production.
Expect the unexpected
Authors: F. Godlee
Journal: BMJ (2009)

Medicine is beset with traps for the unwary: incidental findings, unintended consequences, perverse incentives, symptoms that are easily missed. This week’s journal has its fair share of examples.

Zoe Morris and colleagues ask how often MRI scans of the brain find things they weren’t looking for (doi:10.1136/bmj.b3016). Their meta-analysis concludes that one in every 37 scans over the past 20 years had an incidental finding. In his linked editorial, Aad van der Lugt warns that rates are probably even higher with modern scanners and imaging protocols (doi:10.1136/bmj.b3107). Patients and research participants should be warned beforehand and carefully counselled afterwards. …
Pseudopolymyalgia rheumatica during treatment with enalapril.
Authors: X. Leloet, N. Moore, P. Deshayes
Journal: BMJ (1989)

shown abnormalities ranging from mild portal inflammation to centrizonal collapse with bridging.The course has been suggestive ofa hypersensitivity reaction with a shorter period to develop- ment ofabnormal liver function after re-exposure to the drug.Ours is the first case with typical pathological features of chronic active hepatitis.The evidence strongly implicated cimetidine.In- advertent re-exposure to the drug caused rapid recurrence of jaundice and abnormal liver function values, and withdrawal of cimetidine and treat- ment with prednisone for two months returned these values to normal, although repeat biopsy still showed evidence of chronic active hepatitis.Preexisting chronic active hepatitis exacerbated by cimetidine is unlikely in the absence of other recognised causes of chronic active hepatitis.This case adds to the slowly accumulating evidence implicating cimetidine as a rare but definite hepatotoxin.The low incidence makes monitoring of liver function values unlikely to be cost effective, but when clinical hepatitis occurs cimetidine must be considered a potential villain.
ELECTRIC CONVULSIVE THERAPY AFTER TEN YEARS OF PHARMACOTHERAPY
Authors: LOTHAR B. KALINOWSKY
Journal: American Journal of Psychiatry (1964)

The conclusions from this survey are obvious. Even though modern drugs represent an enormous progress in psychiatry and have increased the number of treatable patients immensely, they have not replaced previous treatments including ECT. Pharmacotherapy has undoubtedly contributed to the great strides made by social psychiatry, but it has been shown by various authors that in some countries these new developments in mental hospitals preceded the introduction of drugs. It was the purpose of this paper to counteract a trend frequently observed in psychiatry to discard established treatments in favor of newer ones. The original overenthusiasm for the new drugs 10 years ago was unjustified. It would be equally unjustified if some present disappointments should lead to their discreditation; but there is no reason to neglect any of the previously available methods. In this paper the indications of pharmacotherapy and ECT have been discussed. It was our aim to show that some indications overlap, that others differ and that judicious use of both methods is necessary for optimal therapeutic results.
Junior doctor died of natural causes, says coroner
Authors: D. Skentelbery
Journal: BMJ (1994)

A young doctor in Britain died of the sudden adult death syndrome after working an 86 hour week, an inquest heard at Warrington last week. Dr Alan Massie, aged 27, of Macclesfield, Cheshire, was on a general practice training scheme at Warrington General Hospital, during which he had complained to his parents about long hours of work and had appeared pale and tired.

He had worked a 56 hour week immediately followed by one of 86 hours in the obstetrics and gynaecology department before his death on 31 January this year. He had worked seven of the eight previous days and three nights, including two unbroken periods of 27 hours and one of 24 hours.

But Professor …
LOW SERUM EICOSAPENTAENOIC ACID–ARACHIDONIC ACID RATIO INDICATES FOLLOWING CARDIOVASCULAR AND LIMB–ISCHEMIC EVENTS IN PATIENTS WITH PERIPHERAL ARTERY DISEASE
Authors: Tetsuji Morishita, Hiroyasu Uzui, Kenichiro Arakawa, Naoki Amaya, Kentaro Ishida, Takehiko Sato, Yoshitomo Fukuoka, Hiroyuki Ikeda, Chiyo Maeda, Machiko Koike, Yusuke Sato, Kaori Hisazaki, Junya Yamaguchi, Jong–Dae Lee, Hiroshi Tada
Journal: Journal of the American College of Cardiology (2013)
Shock Trauma/Critical Care Manual: Initial Assessment and Management
Authors: Robert F. Wilson
Journal: JAMA (1983)

This book is a good teaching manual on the management of trauma and posttraumatic complications. Developed by the Shock Trauma Unit at the Maryland Institute of Emergency Medical Services (MIEMS), this large and long book (594 pages) was designed to provide a practical and ready clinical reference for surgeons, anesthesiologists, critical care specialists, and emergency room physicians. It provides guidelines and outlines on the procedures used at MIEMS for various critical problems, particularly immediate trauma resuscitation, stabilization, diagnosis, and definitive treatment. This book primarily emphasizes blunt injuries in contrast to most other trauma books, whose authors have the greatest experience with penetrating trauma.  Less than half of the book discussed the initial evaluation and management of trauma itself, with special consideration given to burns and gunshot wounds. Much of the remainder of the book deals with organ system failure, infection, nutrition, and various techniques and procedures used either during emergency