tbuckley/cabot-search huggingface dataset:
Methylation of the estrogen receptor-α gene promoter is selectively increased in proliferating human aortic smooth muscle cells
Authors: A Ying
Journal: Cardiovascular Research (2000)

Objective: Atherosclerosis is a multigenic process leading to the progressive occlusion of arteries of mid to large caliber. A key step of the atherogenic process is the proliferation and migration of vascular smooth muscle cells into the intimal layer of the arterial conduit. The phenotype of smooth muscle cells, once within the intima, is known to switch from contractile to de-differentiated, yet the regulation of this switch at the genomic level is unknown. Estrogen has been shown to regulate cell proliferation both for cancer cells and for vascular cells. However, methylation of the estrogen receptor-α gene (ERα) promoter blocks the expression of ERα, and thereby can antagonize the regulatory effect of estrogen on cell proliferation. We sought to determine whether methylation of the ERα is differentially and selectively regulated in contractile versus de-differentiated arterial smooth muscle cells. Methods: We used Southern blot assay, combined bisulfite restriction analysis (Cobra) and restriction landmark genome scanning (RLGS-M) to determine the methylation status of ERα in human aortic smooth muscle cells, either in situ (normal aortic tissue, contractile phenotype), or the same cells explanted from the aorta and cultured in vitro (de-differentiated phenotype). Results: We provide evidence that methylation of the ERα in smooth muscle cells that display a proliferative phenotype is altered relative to the same cells studied within the media of non-atherosclerotic aortas. Thus, the ERα promoter does not appear to be methylated in situ (normal aorta), but becomes methylated in proliferating aortic smooth muscle cells. Using a screening technique, RLGS-M, we show that alteration in methylation associated with the smooth muscle cell phenotypic switch does not seem to require heightened activity of the methyltransferase enzyme, and appears to be selective for the ERα and a limited pool of genes whose CpG island becomes either demethylated or de novo methylated. Conclusions: Our data support the concept that the genome of aortic smooth muscle cells is responsive to environmental conditions, and that DNA methylation, in particular methylation of the ERα, could contribute to the switch in phenotype observed in these cells.
Decreased Gs alpha mRNA levels accompany the fall in Gs and adenylyl cyclase activities in compensated left ventricular hypertrophy. In heart failure, only the impairment in adenylyl cyclase activation progresses.
Authors: L A Chen, D E Vatner, S F Vatner, L Hittinger, C J Homcy
Journal: Journal of Clinical Investigation (1991)

We have previously reported that there is a global reduction in adenylyl cyclase associated with a decrement in Gs functional activity in cardiac sarcolemma from animals with pressure overload-induced hypertrophy and heart failure. This study was performed to determine whether hypertrophy alone in the absence of heart failure is sufficient to promote these changes and whether the superimposition of heart failure intensified these changes. Basal and stimulated adenylyl cyclase and Gs activity, as determined in the S49 cyc- reconstitution assay, were measured in sarcolemma from normal (NL), left ventricular hypertrophy (LVH) and heart failure (HF) animals. Simultaneously, we measured the mRNA level encoding for the Gs alpha subunit. These studies indicate that Gs activity and Gs alpha mRNA are decreased by approximately 30% both in the failing heart and even in the heart with compensated hypertrophy before heart failure develops (Gs activity, pmol cyclic AMP/10 min per microgram, NL 4.2 +/- 0.4, LVH 3.0 +/- 0.2, HF 3.2 +/- 0.3; Gs alpha mRNA, pg/10 micrograms RNA, NL 131 +/- 9.0, LVH 104 +/- 7.4, HF 97.4 +/- 9.1; P less than 0.05 as compared with NL for LVH and HF). Accompanying this decrement in Gs activity is a fall in adenylyl cyclase, both basal and stimulated. However, we also identified a further decrease in adenylyl cyclase without any additional change in Gs or in its alpha subunit mRNA level. This is seen only in the sarcolemma from animals with heart failure as compared with those with compensated LV hypertrophy (e.g., NaF-stimulated activity, pmol cyclic AMP/min per mg, NL 420.2 +/- 17.5, LVH 347.1 +/- 29.6, HF 244.2 +/- 27.3; P less than 0.05 compared with NL for LVH and HF, P less than 0.05 compared with LVH for HF). In summary, these studies indicate that both Gs and adenylyl cyclase activities fall in parallel with the development of LV hypertrophy followed by a further decrement in adenylyl cyclase, independent of Gs, in the setting of heart failure.
Vascular Permeability Factor/Vascular Endothelial Growth Factor: A Critical Cytokine in Tumor Angiogenesis and a Potential Target for Diagnosis and Therapy
Authors: Harold F. Dvorak
Journal: Journal of Clinical Oncology (2002)

Vascular endothelial growth factor A (VEGF-A), the founding member of the vascular permeability factor (VPF)/VEGF family of proteins, is an important angiogenic cytokine with critical roles in tumor angiogenesis. This article reviews the literature with regard to VEGF-A's multiple functions, the mechanisms by which it induces angiogenesis, and its current and projected roles in clinical oncology. VEGF-A is a multifunctional cytokine that is widely expressed by tumor cells and that acts through receptors (VEGFR-1, VEGFR-2, and neuropilin) that are expressed on vascular endothelium and on some other cells. It increases microvascular permeability, induces endothelial cell migration and division, reprograms gene expression, promotes endothelial cell survival, prevents senescence, and induces angiogenesis. Recently, VEGF-A has also been shown to induce lymphangiogenesis. Measurements of circulating levels of VEGF-A may have value in estimating prognosis, and VEGF-A and its receptors are potential targets for therapy. Recognized as the single most important angiogenic cytokine, VEGF-A has a central role in tumor biology and will likely have an important role in future approaches designed to evaluate patient prognosis. It may also become an important target for cancer therapy.
The James D. Bruce Memorial Award Lecture: Is Routine Smallpox Vaccination Necessary?
Authors: Alexander D. Langmuir
Journal: Annals of Internal Medicine (1973)

Meeting Abstracts1 May 1973The James D. Bruce Memorial Award Lecture: Is Routine Smallpox Vaccination Necessary?Alexander D. Langmuir, M.D.Alexander D. Langmuir, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-78-5-812_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptFor more than a century, vaccination has been accepted as the essential measure for the control of smallpox, and, indeed, the elimination of the scourge from the Western world was associated with widespread use of vaccination. In October 1971, however, the Surgeon General of the U.S. Public Health Service recommended that this long-established practice was no longer indicated as a routine procedure.Since that time a serious outbreak of malignant smallpox has occurred in Yugoslavia, and an extensive epidemic has developed in northern India and Bangladesh. In spite of these adverse events, I believe that the Surgeon General's decision was... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Boston, Massachusetts PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1973Volume 78, Issue 5Page: 812-812KeywordsAdverse eventsMedical servicesSurgeons Issue Published: 1 May 1973 PDF DownloadLoading ...
The Genomics Gold Rush
Authors: Eric J. Topol, Sarah S. Murray, Kelly A. Frazer
Journal: JAMA (2007)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
THE TOXICITY OF STREPTOLYSIN O FOR BEATING MAMMALIAN HEART CELLS IN TISSUE CULTURE
Authors: A. Thompson, S. P. Halbert, U. Smith
Journal: The Journal of Experimental Medicine (1970)

Pulsating mammalian myocardial cells were found to be highly susceptible in tissue culture to rapid destruction by streptolysin O. Cessation of beating occurred almost immediately, followed within minutes by multiple cell membrane bleb formation. Parallel with these changes, the cytoplasm became intensely granular and the nuclear membrane apparently thickened when viewed by phase microscopy. At the ultrastructural level, the cell membrane blebs were found to contain relatively small numbers of granular fragments. The endoplasmic reticulum of damaged heart cells was quite swollen, and its contents were considerably condensed. The myofibers were not strikingly altered, but cytoplasmic and mitochondria vacuoles were rather abundant. Cardiac endothelial, kidney epithelial, and fibroblast cells were also susceptible to lysis by this toxin, but the reactions occurred more slowly or bleb formation was less evident. An antiserotonin drug known to be protective against streptolysin-O in vivo (UML-491), did not protect against killing of cardiac cells at the tissue culture level. Serotonin could not be detected in the culture fluid after lysis of cardiac cells by streptolysin O.
A R59W mutation in human protoporphyrinogen oxidase results in decreased enzyme activity and is prevalent in South Africans with variegate porphyria
Authors: Peter N. Meissner, Tamara A. Dailey, Richard J. Hift, Mel Ziman, Anne V. Corrigall, Andrew G. Roberts, Doreen M. Meissner, Ralph E. Kirsch, Harry A. Dailey
Journal: Nature Genetics (1996)
Weight Reduction in Obesity by Outpatient Semistarvation
Authors: Saul M. Genuth, Jamie H. Castro, Victor Vertes
Journal: JAMA (1974)

In a regimen of weight reduction for massively obese patients, all food was withdrawn during one week of hospitalization. The patients were maintained on 45 gm of casein calcium (Casec) and 30 gm of glucose for months on an outpatient basis, with close clinical and biochemical monitoring. Forty-five (60%) of 75 patients lost 18 kg (40 lb) or more. The average loss was 38 kg (85 lb). Men lost 2.1 kg (4.8 lb)/week and women lost 1.4 kg (3.2 lb)/week. No severe chemical derangements occurred. A modest state of catabolism existed, evidenced by an estimated minimum 2-gm negative nitrogen balance and small potassium and phosphate losses. The expected clinical benefits were obtained, and no serious disabilities were encountered as the patients engaged in normal activities. This regimen can be recommended when weight reduction per se is a medical imperative because of diabetes, hypertension, cardiopulmonary disease, or necessary elective surgery. (<i>JAMA</i>230:987-991, 1974)
Gastrointestinal Tract Involvement in Hepatocellular Carcinoma: Clinical, Radiological and Endoscopic Studies
Authors: L T Chen, C Y Chen, C M Jan, W M Wang, T S Lan, M Y Hsieh, G C Liu
Journal: Endoscopy (1990)

Gastrointestinal tract involvement with hepatocellular carcinoma was observed in 8 out of 396 patients (2%) during the course of the disease. Histological involvement was confirmed in 6 cases. All 8 patients were men. The most common clinical presentation was frank gastrointestinal bleeding, which became evident in all cases. Esophageal varices were not seen in any patient. The sites of involvement were the stomach (3), duodenum (4), and jejunum (1). The median time between the diagnosis of primary tumors and gastrointestinal tract involvement was 4.5 months (range: 0 to 12 months). Hematogenous spread was presumed to have occurred in two patients with diffuse-type hepatocellular carcinoma, one of whom had main portal vein thrombosis. Direct invasion by contiguous neoplasm was the major mode of gastrointestinal tract involvement. This complication is more likely to develop in patients with large, subcapsular, massive type hepatocellular carcinoma treated by transcatheter arterial embolization and/or intra-arterial chemotherapy. The median survival after the diagnosis of gastrointestinal involvement was 1 month (2 weeks-4 months).
Anti-apoptotic cardioprotective effects of SHP-1 gene silencing against ischemia–reperfusion injury: Use of deoxycholic acid-modified low molecular weight polyethyleneimine as a cardiac siRNA-carrier
Authors: Dongkyu Kim, Jueun Hong, Hyung-Ho Moon, Hye Yeong Nam, Hyejung Mok, Ji Hoon Jeong, Sung Wan Kim, Donghoon Choi, Sun Hwa Kim
Journal: Journal of Controlled Release (2013)
To Biopsy or Not to Biopsy
Authors: Donald M. Kurtz
Journal: JAMA (1970)

<h3>To the Editor:—</h3> Much discussion in the recent literature concerns Sternberg-Reed cells in tissue sections from patients with conditions other than Hodgkin's disease.<sup>1-3</sup>These cases have been especially perplexing in patients with abnormal lymph node proliferations such as infectious mononucleosis, postvaccinal lymphadenitis, and drug-induced lymphoid hyperplasias. Several investigators, faced with differentiating serious, systemic, neoplastic diseases (Hodgkin's type) from those already mentioned, have resorted to nodal biopsy and histologic appraisal. From review of their published photomicrographs, perplexing problems of clinical-pathological differentiation are noted.<sup>4</sup> As a practicing pathologist, interested in arriving at a rapid, reliable tissue diagnoses to provide definitive therapy, I am hesitant to recommend tissue biopsy in those conditions in which interpretation is difficult even for experienced pathologists and could lead to clinically unnecessary radiation or chemotherapy. It seems that time is the best therapy for those conditions. That is not to say that these patients should be
UN mission finds evidence of war crimes on both sides of Gaza conflict
Authors: J. Zarocostas
Journal: BMJ (2009)

Israel’s armed forces committed actions amounting to war crimes and possibly crimes against humanity during the recent Gaza conflict, says a UN report. It documents deliberate attacks on hospitals and other medical facilities. 

The report, which was compiled by an independent fact finding mission, also concludes indiscriminate rocket and mortar attacks by Palestinian armed groups into Southern Israel would constitute war crimes, and may amount to crimes against humanity.

The mission found that the military operation by Israel from 27 December to 18 January, 2009, “was a deliberate attack designed to punish, humiliate and terrorize a civilian population, radically diminish its local economic capacity and to force upon it an ever increasing sense of dependency and vulnerability.”

An Israeli foreign ministry spokesman said, “Israel did not feel able to cooperate with the fact finding mission because its mandate was clearly one sided.”

Investigators assert that the …
Outcomes and economics associated with use of abciximab in patients ≥70 years undergoing coronary interventions
Authors: C.L. Lucore, R.V. Trask, G.J. Mashkel, R.L Kacich, K.J. Rocha-Singh, H.W. Moses, F.L. Mikell, M.E. Shelton, R.W. Ligon
Journal: Journal of the American College of Cardiology (1998)
THE EFFECT OF SODIUM CHLORIDE DEPLETION ON BLOOD PRESSURE AND TETRAETHYLAMMONIUM CHLORIDE RESPONSE IN HYPERTENSION 1
Authors: William W. Stead, Morton F. Reiser, Samuel Rapoport, Eugene B. Ferris
Journal: Journal of Clinical Investigation (1948)

A number of investigators have presented evi- dence to show that a diet poor in sodium may lower the blood pressure of hypertensive patients (1-7).Others have concluded that the blood pressure changes observed in association with sodium restriction are fortuitous (8-13).Recently Perera (6) has shown a small but significant de- crease in the early morning blood pressure of a group of hospitalized hypertensive patients in re- sponse to a low sodium intake.In his patients the fall in blood pressure was not accompanied by a change in plasma volume, cardiac output, or serum sodium concentration.In view of the conflicting evidence, it seemed worthwhile to learn first whether more rigid salt deprivation could produce more definite changes in the daily random blood pressure than those pre- viously reported; and second, to define, if possible, the physiologic mechanism concerned in the changes associated with drastic shifts in the sodium balance.It was thought that information on the latter problem could be obtained by observing the effects of changes in salt balance not only on the random blood pressure, but also on the response of the blood pressure to the tetraethylammonium ion.Since it has been shown that this drug blocks the transmission of impulses by the autonomic ganglia (14, 15), it should be possible to evaluate the rela- tive r6les of neurogenic and humoral tone in the maintenance of the blood pressure (16)(17)(18)(19)(20). MATERIAL AND METHODSTwelve patients with severe and persistent hypertension were studied to determine the effects of severe sodium
Intrauterine Surgical Procedures during Hysteroscopy
Authors: K. Edström
Journal: Endoscopy (1974)

A hysteroscopy technique is described which enables intrauterine and transcervical operative procedures to be carried out with ease and accuracy. The uterine cavity is expanded by a viscous solution of dextran which provides several advantages over other media. Techniques for resection of intrauterine adhesions and uterine septa are described and case reports are given. The apparent anti-adhesive properties of dextran would be considered an advantage in most operative procedures, possibly with the exception of transcervical electrocautery for tubal sterilization.
Heterosexual Transmission of HIV-Reply
Authors: Mary E. Guinan
Journal: JAMA (1993)

<h3>In Reply.</h3> —Drs Rodrigues and Garcia Moreno do not define safe sex, and therefore, their recommendations are unclear. The risk of acquisition of HIV increases with increasing number of sex partners. We should teach our children that having intercourse with multiple partners is unhealthy and also how to protect themselves if they choose to have sex. Both messages are also essential for adults. Which one is emphasized may depend on the particular clinical situation, but neither message should be excluded.
ln-111 Labeled Monoclonal Anti-Carcinoembryonic Antigen Antibody (ZCE025) in the Immunoscintigraphlc Imaging of Metastatic Antigen-Producing Adenocarcinomas
Authors: MANSOOR N. SALEH, RICHARD H. WHEELER, JEANNETTE Y. LEE, M B KHAZAELI, MICHAEL W. UNGER, CHARLES H. RUSSELL, ALBERT F. LoBUGLIO
Journal: Clinical Nuclear Medicine (1991)

The carcinoembryonic antigen (CEA) is a clinically useful marker since it is expressed by adenocarcinomas of diverse origin. Detection and quantitation of circulating CEA levels is used to follow the clinical course of metastatic adenocarcinoma. In this phase I study, the toxicity, pharmacokinetics, and optimal imaging dose of an In-111 labeled monoclonal anti-CEA antibody (ZCE025) was studied in patients with colorectal carcinoma or any CEA-producing tumor. Twenty-four of 26 evaluable patients (92%) demonstrated at least one site of tumor-specific antibody uptake. Sixty-seven sites of metastatic cancer were identified by conventional diagnostic studies. Twenty-nine (43%) of these sites were demonstrable by radioimmune imaging using ZCE025. Twenty-five additional sites of antibody uptake were observed but could not be associated with metastatic deposits. Lymph node and visceral metastases were visualized more frequently than bone, subcutaneous, lung, or liver metastases. Neither tumor size nor antibody dose (2.5-40 mg) appeared to influence the frequency of tumor imaging. The pharmacokinetics of the In-111 labeled antibody fitted a two-compartment model, and patients receiving less than 10 mg of antibody showed a faster clearance of the antibody than those who received greater than 10 mg.
THE PATHOLOGY OF CHROMIDROSIS.
Authors: M. L. HEIDINGSFELD
Journal: JAMA (1902)

Thename chromidrosis implies an anomalous secretion from the sudoriferous or sweat glands characterized by colored perspiration. Its occurrence is exceedingly infrequent; Foot,<sup>1</sup>in a careful review of the literature dating from 1709 to 1868, has been able to enumerate but 38 cases, to many of which a doubtful character must necessarily be attributed. Fowie's<sup>2</sup>careful historical review, 1709-1891, does not add many well-defined cases, and surprisingly few have been reported in the literature of recent years. Its marked infrequency can be best appreciated by referring to the Van Harlingen's<sup>3</sup>statement, that "it is so rare as to be a curiosity rather than a disease." Those who have written on the subject, almost without exception, are of one accord as to nature, and attribute to the condition a disorder, functional or otherwise, of the sweat glands. This is especially evident in all the text-books of skin diseases, where
Unusual Causes for Abnormal Hepatobiliary Scans
Authors: LEONIE GORDON, MICHAEL C. ELLIS, STEPHEN I. SCHABEL
Journal: Clinical Nuclear Medicine (1983)

Cholescintigraphy with Tc-99m iminodiacetic acid (IDA) agents has proved to be a convenient, non-invasive method for evaluating patients with suspected cholecystitis. (1,2) We recently examined two patients who were being evaluated for abdominal pain. The etiology of the two abnormal cholescintigrams was later proven to be due to nonhepatobiliary pathology.
Bilateral Tubal Gestation
Authors: B. B. Hickey
Journal: BMJ (1948)

ANAEMIA TREATED WITH INTRAVENOUS IRON BRICISH ingly she was given a transfusion of 3 pints (1.7 litres) of blood, which raised the haemoglobin level to 68 %.She was dis- charged on Aug. 7, and continued to take ferrous sulphate, 3 gr.three times a day, as an out-patient.
THE RELATION OF PATHOLOGIC PHYSIOLOGY TO INTERNAL MEDICINE
Authors: ALBION WALTER HEWLETT
Journal: JAMA (1913)

For surgery, pathologic anatomy has furnished a basis for both diagnosis and treatment. The tumor or foreign body can be taken out, the inflamed part incised or removed, the obstructed passage dilated or the hollow viscus drained. For internal medicine, pathologic anatomy has been equally important as a fundamental basis in the diagnosis of disease; and it has furnished an exact demonstrable basis for many symptom-complexes. So far as treatment is concerned, however, its direct value is far less evident, for pathologic changes in structure are but rarely influenced by medicine. The clinician schooled in pathologic anatomy is therefore apt to be led into a position of therapeutic nihilism, placing his reliance chiefly on the curative forces of Nature which are to be assisted here and there by medical care and by nursing. This attitude, which was prominent in certain clinical schools during the last century, found its expression in