tbuckley/cabot-search huggingface dataset:
Use of Echocardiography in Patients with Prolapsed Mitral Valve
Authors: JAMES C. DILLON, CHARLES L. HAINE, SONIA CHANG, HARVEY FEIGENBAUM
Journal: Circulation (1971)

The echocardiographic findings are described for five patients who had the prolapsed mitral valve syndrome, proven by cardiac catheterization and angiocardiography. In all five patients, the echocardiograms demonstrated posterior displacement of the posterior mitral leaflet during systole. In four of the patients there was also posterior displacement of the anterior leaflet. Four of the five patients had mitral insufficiency, demonstrated by cineangiography. These four patients demonstrated echocardiographic separation of the anterior and posterior leaflets of the mitral valve in late systole. The fifth patient did not show this separation, and she had no mitral insufficiency by selective cineangiography. Two patients were given amyl nitrite during the echocardiographic examination, and the echogram showed earlier separation of the anterior and posterior leaflets as well as lengthening of the murmur. Echocardiography should be a very useful noninvasive, yet direct, method for diagnosing, studying, and following patients with prolapse of the mitral valve.
Genetic evidence for a common enzyme catalyzing the second step in the degradation of proline and hydroxyproline.
Authors: D Valle, S I Goodman, S C Harris, J M Phang
Journal: Journal of Clinical Investigation (1979)

The initial step in the degradation pathways of proline and hydroxyproline is catalyzed by proline oxidase and hydroxyproline oxidase, yielding delta 1-pyrroline-5-carboxylate and delta 1-pyrroline-3-hydroxy-5-carboxylate, respectively. The second step is the oxidation of delta 1-pyrroline-5-carboxylate to glutamate and delta 1-pyrroline-3-hydroxy-5-carboxylate to gamma-hydroxy-glutamate. To determine if this second step in the degradation of proline and hydroxyproline is catalyzed by a common or by separate enzyme(s), we developed a radioisotopic assay for delta 1-pyrroline-3-hydroxy-5-carboxylate dehydrogenase activity. We then compared delta1-pyrroline-3-hydroxy-5-carboxylate dehydrogenase activity with that of delta 1-pyrroline-5-carboxylate dehydrogenase in fibroblasts and leukocytes from type II hyperprolinemia patients, heterozygotes, and controls. We found that cells from type II hyperprolinemia patients were deficient in both dehydrogenase activities. Furthermore, these activities were highly correlated over the range found in the normals, heterozygotes, and patients. We conclude from these data that a common delta 1-pyrroline-5-carboxylate dehydrogenase catalyzes the oxidation of both delta 1-pyrroline-5-carboxylate and delta 1-pyrroline-3-hydroxy-5-carboxylate, and that this activity is deficient in type II hyperprolinemia.
Helicobacter pylori infection in Africa and Europe: enigma of host genetics
Authors: S Hellmig
Journal: Gut (2003)

Helicobacter pylori infection is one of the most common bacterial infections. The prevalence varies from 25–50% in developed countries to 70–90% in the third world.1 Despite improved treatment modalities, H pylori related gastrointestinal pathology, in common with gastritis, peptic ulcers and consecutive bleeding events, gastric MALT lymphoma, or carcinoma, remains a major burden on Western health systems. In the USA, approximately four million people have active peptic ulcers and about 350 000 new cases are diagnosed each year. Four times as many duodenal ulcers as gastric ulcers are diagnosed.2 Epidemiological evidence suggests that both infection with H pylori and the consecutive development of clinically relevant pathology are influenced by genetic predisposition as only a fraction of exposed individuals develop infection and likewise a fraction …
Caffeine and Benign Breast Disease-Reply
Authors: Flora Lubin
Journal: JAMA (1985)

<h3>In Reply.—</h3> Dr Minton's letter shows a basic misunderstanding of our study's aims and its methods. Our objective was to investigate if there is an etiological association between methylxanthine intake and all types of well-differentiated benign breast diseases, diagnosed by histopathological findings after biopsy. We did not evaluate the possible therapeutic effect of a methylxanthine-free diet. His letter states that fibroadenoma, nonspecific histopathology, and granuloma are irrelevant in a study evaluating the effects of caffeine on benign breast disease. Yet Minton has reported that methylxanthine acts on breast tissue by increasing the level of cyclic adenosine monophosphate and cyclic guanosine monophosphate and shows that this effect is common to all benign breast disease, including fibroadenoma.<sup>1</sup>Furthermore, he finds this effect peaks in breast cancer tissue. Our study population, graded by Black's system of degree of ductal atypia (from grade 1, normotypic, through grades 3 and 4, precancerous mastopathy, to
Drugs Five Years Later: Rifampin
Authors: W. EUGENE SANDERS
Journal: Annals of Internal Medicine (1976)

In 1971, rifampin was approved for treatment of pulmonary tuberculosis and asymptomatic carriers of Neisseria meningitidis. At present, the approved indications remain the same. However, rifampin in conjunction with at least one other antituberculous drug may be of great value in therapy of extrapulmonary tuberculosis and infections due to other susceptible mycobacteria. In addition, results of clinical trials in leprosy have been highly encouraging. Rifampin appears to induce light chain proteinuria in a majority of patients and has been implicated in suppression of both humoral and cell-mediated immune responses. However, these effects appear to have been of little consequence to treated patients. A variety of possibly immunologically mediated reactions to rifampin has been closely associated with irregular administration of the drug. These reactions and hepatic toxicity may be preventable in many patients. Rifampin or one of its congeners, alone or in combination with other antibiotics, may prove useful in treatment of various infectious, and possibly malignant, diseases.
Relationship Between Supranormal Oxygen Tension and Outcome After Resuscitation From Cardiac Arrest
Authors: J. Hope Kilgannon, Alan E. Jones, Joseph E. Parrillo, R. Phillip Dellinger, Barry Milcarek, Krystal Hunter, Nathan I. Shapiro, Stephen Trzeciak
Journal: Circulation (2011)

Laboratory and recent clinical data suggest that hyperoxemia after resuscitation from cardiac arrest is harmful; however, it remains unclear if the risk of adverse outcome is a threshold effect at a specific supranormal oxygen tension, or is a dose-dependent association. We aimed to define the relationship between supranormal oxygen tension and outcome in postresuscitation patients.This was a multicenter cohort study using the Project IMPACT database (intensive care units at 120 US hospitals). Inclusion criteria were age >17 years, nontrauma, cardiopulmonary resuscitation preceding intensive care unit arrival, and postresuscitation arterial blood gas obtained. We excluded patients with hypoxia or severe oxygenation impairment. We defined the exposure by the highest partial pressure of arterial oxygen (PaO(2)) over the first 24 hours in the ICU. The primary outcome measure was in-hospital mortality. We tested the association between PaO(2) (continuous variable) and mortality using multivariable logistic regression adjusted for patient-oriented covariates and potential hospital effects. Of 4459 patients, 54% died. The median postresuscitation PaO(2) was 231 (interquartile range 149 to 349) mm Hg. Over ascending ranges of oxygen tension, we found significant linear trends of increasing in-hospital mortality and decreasing survival as functionally independent. On multivariable analysis, a 100 mm Hg increase in PaO(2) was associated with a 24% increase in mortality risk (odds ratio 1.24 [95% confidence interval 1.18 to 1.31]. We observed no evidence supporting a single threshold for harm from supranormal oxygen tension.In this large sample of postresuscitation patients, we found a dose-dependent association between supranormal oxygen tension and risk of in-hospital death.
1174 ASSOCIATION OF IL28B GENOTYPE WITH VIROLOGICAL RESPONSE TO PEGYLATED-INTERFERON PLUS RIBAVIRIN IN PATIENTS WITH ADVANCED CHRONIC HEPATITIS C ENROLLED IN THE HALT-C TRIAL
Authors: T. O'Brien, H. Bonkovsky, R. Pfeiffer, R. Chung, J. Everhart, M. Shiffman, J. Sninsky, T. Morgan
Journal: Journal of Hepatology (2010)
Percutaneous Coronary Aneurysm Obliteration Using a Novel Pericardium-Covered Stent
Authors: Marco Ferlini, Filippo Russo, Barbara Marinoni, Alessandra Repetto, Umberto Canosi, Maurizio Ferrario, Luigi Oltrona Visconti, Ezio Bramucci
Journal: Journal of the American College of Cardiology (2010)
Composition of Fluid in Twelve Cysts of a Polycystic Kidney
Authors: Kenneth D. Gardner
Journal: New England Journal of Medicine (1969)

Analyses of the chemical composition of fluid in 12 cysts of a polycystic kidney disclosed marked variations in the concentrations of selected cations, glucose, urea and creatinine. The concentrations of sodium ranged from 3.1 to 150.0 mEq per liter, of potassium from 4.6 to 58.1 mEq per liter, of hydrogen from 13 to 9800 nanoEq per liter and of creatinine from 11 to 87 mg per 100 ml. The concentrations of sodium varied directly with those of calcium and inversely with those of potassium, hydrogen, ammonium and magnesium, suggesting that the cyst walls were functioning as either proximal or distal nephrons. In cysts whose contents reflected distal tubular activity, amino acids contributed 50 to 100 mOsm per kilogram of water to the osmotic activity of the fluid.
Hypophysiotropic and neuromodulatory regulation of adrenocorticotropin in the human fetal pituitary gland.
Authors: Z Blumenfeld, R B Jaffe
Journal: Journal of Clinical Investigation (1986)

Synthetic human corticotropin-releasing factor (hCRF) stimulated ACTH secretion by human fetal pituitaries in superfusion and dispersed human fetal pituitary cells cultured on an extracellular matrix in static incubation from 14 to 23 wk gestational age. The action of hCRF in vitro was potentiated by arginine vasopressin (AVP) at all ages studied. 8-Br-cAMP induced a response similar to hCRF. The AVP effect on ACTH was synergistic with both CRF and 8-Br-cAMP. hCRF-mediated secretion of ACTH was noncompetitively inhibited by 24-h pretreatment, or by 3-h concomitant treatment, with dexamethasone. Neither oxytocin, catecholamines, prostaglandins, nor indomethacin exerted significant effects on ACTH secretion, either alone or in combination with hCRF or AVP during the gestational ages studied. These results support a physiologic role for CRF in the regulation of secretion by corticotropic cells as early as 14 wk gestation, by which time corticotropes and ability to secrete ACTH have been demonstrated.
New General Medical Council president elected
Authors: Caroline White
Journal: BMJ (2001)

Professor Graeme Catto has been elected to succeed Donald Irvine as president of the General Medical Council, the body that regulates the UK medical profession.

Ninety three council members out of a total of 104 voted in the election on Tuesday by single transferable vote. One of six candidates for the presidency, Professor Catto, won by a wide margin, with 47 votes.

Professor James Drife came second with 17 votes, followed by Professor Wendy Savage with 13, Dr Brian Keighley with eight, Mr Olusala Oni with six, and Dr Shiv Pande with two. …
Patients on lipid-lowering therapy at the time of a myocardial infarction have smaller infarcts: further evidence to suggest a salutary effect in acute coronary syndromes
Authors: Herbert D. Aronow, Thomas McRae, Marlin J. Quinn, Eric J. Topol, Michael Lincoff, Penny L. Houghtaling, Michael S. Lauer
Journal: Journal of the American College of Cardiology (2002)
Human 6-Sulfo LacNAc-Expressing Dendritic Cells Are Principal Producers of Early Interleukin-12 and Are Controlled by Erythrocytes
Authors: Knut Schäkel, Matthias von Kietzell, Anja Hänsel, Annette Ebling, Livia Schulze, Michael Haase, Christian Semmler, Marika Sarfati, A. Neil Barclay, Gwendalyn J. Randolph, Michael Meurer, E. Peter Rieber
Journal: Immunity (2006)
Acetylated Low-Density Lipoprotein Stimulates Human Vascular Smooth Muscle Cell Calcification by Promoting Osteoblastic Differentiation and Inhibiting Phagocytosis
Authors: D. Proudfoot, J.D. Davies, J.N. Skepper, P.L. Weissberg, C.M. Shanahan
Journal: Circulation (2002)

Background— Vascular smooth muscle cells (VSMCs) in atherosclerotic lesions display an osteogenic phenotype, and calcification commonly occurs in association with lipid. We therefore tested the hypothesis that lipid components in atherosclerotic lesions influenced VSMC phenotype and calcification using an in vitro model of calcification. Methods and Results— In situ hybridization of human atherosclerotic plaques (n=10) collected from patients undergoing carotid endarterectomy demonstrated that subsets of lipid-filled VSMCs adjacent to sites of calcification expressed alkaline phosphatase, bone Gla protein, and bone sialoprotein, suggesting an osteogenic phenotype. Treatment of VSMCs in culture with acetylated low-density lipoprotein (acLDL) or lipoprotein-deficient serum altered the time course of bone-associated protein gene expression and calcification. AcLDL increased nodule calcification 3-fold, whereas lipoprotein-deficient serum significantly inhibited it. Reverse transcriptase–polymerase chain reaction and Western analysis demonstrated the presence of the acLDL receptor, SRA1, exclusively in calcifying nodular VSMCs, and blockade of SRA with polyinosinic acid inhibited acLDL-induced calcification. Because apoptotic bodies can serve as nucleation sites for calcification, we investigated whether acLDL could stimulate apoptosis in nodules. Apoptosis of nodular VSMCs was unaltered, but the number of apoptotic bodies per nodule increased ≈3-fold, implying a defect in phagocytosis. Consistent with these observations, binding of apoptotic bodies to VSMCs was decreased in the presence of acLDL. Conclusions— These studies suggest that modified lipoproteins stimulate calcification by enhancing osteogenic differentiation of VSMCs and by a novel mechanism whereby acLDL interacts with SRA on VSMCs and blocks phagocytic removal of apoptotic bodies.
Physician-Assisted Suicide
Authors: Courtney Campbell
Journal: JAMA (1995)

<h3>To the Editor.</h3> —The article by Ms Alpers and Dr Lo<sup>1</sup>leaves readers with erroneous impressions regarding Oregon's Death With Dignity Act. We question whether their strategies for implementation will achieve their stated goal of improving care for terminally ill patients. The Death With Dignity Act did not legalize physician "assisted suicide" in Oregon, contrary to both the title and content of the essay. Assistance in suicide remains illegal under a 1983 Oregon statute.<sup>2</sup>The Death with Dignity Act explicitly states that the provision by a physician of patient-requested prescriptive medications to end life does not constitute assisted suicide. Moreover, it is misleading to characterize the act as authorizing physician assistance in dying, an approach that diminishes the significance of other caregivers in the process, including consultants, psychiatrists, nurses, pharmacists, and institutions. Alpers and Lo give physicians an unwarranted professional primacy, which we believe will lead not to
Induction of DNA Synthesis by a Single Transient Mechanical Stimulus of Human Vascular Smooth Muscle Cells
Authors: George C. Cheng, Peter Libby, Alan J. Grodzinsky, Richard T. Lee
Journal: Circulation (1996)

Background Although mechanical vascular injury leads to smooth muscle cell proliferation that contributes to restenosis after balloon angioplasty, the role of the single transient mechanical stimulation of smooth muscle cells in this process is unknown. Methods and Results To test the hypothesis that a single transient mechanical stimulus can increase DNA synthesis, human vascular smooth muscle cells cultured in a three-dimensional collagen gel system were subjected to transient compression. Transient compression (5-minute duration) of smooth muscle cell–collagen gel cultures in defined serum-free conditions led to delayed increases in [ 3 H]thymidine incorporation. At 12 to 24 hours after compression, there was a 3.3±0.5-fold ( P &lt;.001 versus control) and 3.0±0.6-fold ( P &lt;.002 versus control) increase for 60% and 80% strain, respectively; at 24 to 36 hours after compression, there was a 1.8±0.5-fold ( P &lt;.05 versus control) and 4.3±0.8-fold ( P &lt;.001 versus control) increase. Also, serum-free media conditioned by transiently compressed gel cultures induced DNA synthesis in control, unstimulated smooth muscle cell cultures, suggesting the release of growth factors by transient compression. Although neutralizing antibodies against platelet-derived growth factor did not affect the mechanical induction of DNA synthesis, a neutralizing monoclonal antibody against fibroblast growth factor–2 (FGF-2) decreased this induction by 89% and completely blocked the increase in DNA synthesis caused by media conditioned by transiently compressed gels. Media conditioned by transient compression contained elevated levels of FGF-2 (17±5 versus 2±2 pg/mL for control, P &lt;.005) with no increase in lactate dehydrogenase activity, suggesting release of FGF-2 with sublethal cellular injury. Conclusions A single transient mechanical stimulus increases DNA synthesis in human vascular smooth muscle cells, in part by autocrine or paracrine FGF-2 release.
INCIDENCE, PREDICTORS AND LONG-TERM IMPLICATION OF ATRIAL FLUTTER AFTER LUNG TRANSPLANTATION
Authors: Peyman N. Azadani, Uday K. Kumar, Yanfei Yang, Melvin M. Scheinman, Charles W. Hoopes, Gregory Marcus, Celia Rifkin, Jeffrey E. Olgin, Byron K. Lee
Journal: Journal of the American College of Cardiology (2011)
Atherosclerosis-related responses to cigarette smoking in the baboon.
Authors: W R Rogers, R L Bass, D E Johnson, A W Kruski, C A McMahan, M M Montiel, G E Mott, R L Wilbur, H C McGill
Journal: Circulation (1980)

Thirty-six young adult male baboons (Papio cynocephalus) were fed an atherogenic diet (40% calories from lard, 1.5 mg cholesterol/kcal) and taught to puff by operant conditioning with water rewards. Eighteen baboons (smokers) were assigned randomly to smoke 43 cigarettes a day, and 18 baboons (shams) were assigned randomly to puff air under conditions equivalent to those of the experimental group. During months 14-19 of smoking, cigarette-smoking baboons had significantly higher carbon monoxide and thiocyanate concentrations in blood and cotinine concentrations in urine. There were no significant differences in serum total cholesterol, VLDL + LDL cholesterol, HDL cholesterol or triglyceride concentrations of smokers and shams. Smoking baboons had significantly higher fasting blood glucose concentrations and lymphocyte counts. Platelet count, platelet aggregation, food and water intake, and body weight were not significantly different in the two groups.
Serum prostacyclin stabilizing factor is identical to apolipoprotein A-I (Apo A-I). A novel function of Apo A-I.
Authors: Y Yui, T Aoyama, H Morishita, M Takahashi, Y Takatsu, C Kawai
Journal: Journal of Clinical Investigation (1988)

Serum PGI2 stabilizing factor (PSF) was purified from human serum to a single protein with a molecular weight of 28,000 D by SDS-PAGE. Analyses of NH2-terminal sequence (32 residues), COOH-terminal sequence (3 residues) and the composition of amino acids disclosed its homology with human apolipoprotein A-I (Apo A-I), a major apolipoprotein of HDL. Apolipoprotein A-II, C-I, C-II, C-III, D and E, as well as LDL, and VLDL did not possess this activity. The alpha-helix structure of Apo A-I is necessary for the binding of PGI2. HDL and nascent HDL reconstituted from Apo A-I and phospholipid significantly prolonged the half-life of PGI2. PGI2 stabilization by HDL and Apo A-I may be an important protective action against the accumulation of platelet thrombi at sites of vascular damage. The beneficial effect of HDL in the prevention of coronary artery disease may be partly due to this action.
Abstract 475: GATA3 mutations in breast cancer
Authors: Motoki Takaku, Aleksandra Adomas, Sara A. Grimm, Shimbo Takashi, Paul A. Wade
Journal: Cancer Research (2014)

Abstract Breast cancer is one of the most common cancers in women worldwide, resulting in over 400,000 deaths per year. Approximately 90% of breast cancers occur in women who have no family history of breast cancer, indicating that most breast cancers occur following spontaneous mutations resulting from the aging process or the action of environmental agents. Breast cancers can be divided into several subtypes base on gene expression profiles. Luminal breast cancer, the most common subtype, is characterized by expression of estrogen receptor alpha (ER-alpha). The zinc finger transcription factor GATA3, which is known as a regulator of mammary gland development, is frequently expressed in luminal breast cancer cells, and its expression is highly correlated with ER-alpha. In breast cancers, the expression levels of GATA3 directly correlate with favorable prognosis, and its ectopic expression leads to the suppression of tumor metastasis. Comprehensive genomic analysis of breast tumors has revealed frequent somatic mutations of GATA3 in luminal breast cancers. However it is unclear how these GATA3 mutations affect the biological properties of breast cancer. These mutations are located at exclusively in exons 5 and 6 that encode the carboxyl terminus of the protein. Exon 5 contains the second of two zinc finger domains (ZnF2), which is important for the DNA binding activity of GATA3. Exon 6 has no previously described biochemical function. In this study, we focus on two mutations found in cancer patients - a frame shift at tyrosine 345 (Y345fs) and a frame shift at arginine 330 (R330fs). These two mutants are of particular interest as they produce truncated proteins, and both mutants lack exon 6. Y345fs preserves ZnF2, while R330fs interrupts ZnF2. These two mutants permit dissection of the molecular outcomes flowing from loss of exon 6 (Y345fs) versus the combination of loss of ZnF2 and exon 6 (R330fs). To assess the impact of these mutations, we established breast cancer cells expressing Y345fs and R330fs respectively, and analyzed their phenotype at the cellular and molecular levels. These studies begin to address the biochemical and functional outcomes of commonly occurring mutations in breast cancer. Citation Format: Motoki Takaku, Aleksandra Adomas, Sara A. Grimm, Shimbo Takashi, Paul A. Wade. GATA3 mutations in breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 475. doi:10.1158/1538-7445.AM2014-475