tbuckley/cabot-search huggingface dataset:
Estrogens and Cardiovascular Risk
Authors: Meir Stampfer, Graham Colditz
Journal: JAMA (1988)

To the Editor.  —We were surprised to see our recent study 1 badly misrepresented in the title and lead-in of the MEDICAL NEWS & PERSPECTIVES story entitled Will Epidemiology Answer the Estrogen Question? 2 The story appeared to suggest that this study questioned the cardiovascular protection from postmenopausal estrogen therapy. On the contrary, that study confirmed the marked protection conferred by replacement hormones among women after bilateral oophorectomy. It did not directly address the issue for women with natural menopause, but an earlier report from the Nurses' Health Study 3 showed a substantial protective effect among those women as well. The main focus of the recent work was to show that, contrary to popular belief, cessation of menses is not accompanied by an abrupt increase in risk of heart disease. This finding in no way suggests that postmenopausal estrogen therapy would not have a benefit. As we pointed out earlier,
Effects of Intraaortic Balloon Counterpulsation on the Severity of Myocardial Ischemic Injury following Acute Coronary Occlusion
Authors: PETER R. MAROKO, EUGENE F. BERNSTEIN, PETER LIBBY, GIACOMO A. DELARIA, JAMES W. COVELL, JOHN ROSS, EUGENE BRAUNWALD
Journal: Circulation (1972)

The effects of intraaortic balloon counterpulsation (IABC) on the magnitude and severity of myocardial ischemic injury were studied in 19 dogs following acute coronary occlusion and in two patients with cardiogenic shock. In the experimental group, epicardial electrocardiograms were taken from 10-14 sites on the anterior surface of the left ventricle following occlusion of the left anterior descending coronary artery or its apical branch. The average S-T-segment elevation ([see Equation in PDF File]) was used as an index of the magnitude of myocardial ischemic injury. In six dogs, two successive 20-min occlusions were performed, and IABC was started prior to the second occlusion. [see Equation in PDF File] 15 min following occlusion decreased from 3.3 ± 0.9 mv after the control occlusion to 1.4 ± 0.4 mv ( P &lt; 0.01) after the occlusion with IABC. In three dogs in which the occlusion was maintained and IABC initiated 30 min later, [see Equation in PDF File] decreased from 1.2 to 0.6 mv. In six dogs in which IABC was started 3 hours after occlusion, it induced a reduction of [see Equation in PDF File] from 4.2 ± 1.1 to 2.8 ± 1.0 mv ( P &lt; 0.01). In four dogs, ischemic injury was augmented by isoproterenol infusion (0.25 µg/kg/min), and while continuing the infusion IABC was initiated. It reduced [see Equation in PDF File] from 8.0 ± 1.9 to 5.7 ± 1.8 mv ( P &lt; 0.05). Thus, IABC reduced the magnitude and extent of myocardial ischemic injury after experimental coronary occlusion, both when IABC was employed prior to, and 3 hours following, coronary occlusion. IABC was also effective in reducing myocardial ischemic injury which had been increased by isoproterenol infusion. Employing a noninvasive technic, which utilizes 35 electrodes on the thorax, the effects of IABC were examined in two patients with cardiogenic shock associated with acute myocardial infarction. Preliminary observations in these patients confirmed the experimental results indicating that IABC reduced myocardial ischemic injury.
The calcium-binding protein calreticulin is a major constituent of lytic granules in cytolytic T lymphocytes.
Authors: M Dupuis, E Schaerer, K H Krause, J Tschopp
Journal: The Journal of Experimental Medicine (1993)

Cytolytic T lymphocytes (CTL), natural killer cells, and lymphokine-activated killer (LAK) cells are cytolytic cells known to release the cytolytic protein perforin and a family of proteases, named granzymes, from cytoplasmic stores upon interaction with target cells. We now report the purification of an additional major 60-kD granule-associated protein (grp 60) from human LAK cells and from mouse cytolytic T cells. The NH2-terminal amino acid sequence of the polypeptide was found to be identical to calreticulin. Calreticulin is a calcium storage protein and carries a COOH-terminal KDEL sequence, known to act as a retention signal for proteins destined to the lumen of the endoplasmic reticulum. In CTLs, however, calreticulin colocalizes with the lytic perforin to the lysosome-like secretory granules, as confirmed by double label immunofluorescence confocal microscopy. Moreover, when the release of granule-associated proteins was triggered by stimulation of the T cell receptor complex, calreticulin was released along with granzymes A and D. Since perforin is activated and becomes lytic in the presence of calcium, we propose that the role of calreticulin is to prevent organelle autolysis due to the protein's calcium chelator capacity.
Pharmacological response of human cardiomyocytes derived from virus-free induced pluripotent stem cells
Authors: Ashish Mehta, Ying Ying Chung, Alvin Ng, Fahamy Iskandar, Shirhan Atan, Heming Wei, Greg Dusting, William Sun, Philip Wong, Winston Shim
Journal: Cardiovascular Research (2011)

AimsGeneration of human induced pluripotent stem cell (hiPSC) lines by reprogramming of fibroblast cells with virus-free methods offers unique opportunities for translational cardiovascular medicine. The aim of the study was to reprogramme fibroblast cells to hiPSCs and to study cardiomyogenic properties and ion channel characteristics of the virus-free hiPSC-derived cardiomyocytes.
Fitness Standards for the Transport Industries
Authors: Tim Carter
Journal: Journal of the Royal Society of Medicine (2001)

The fitness standards required for drivers in the transport industries are discussed. Ways of reducing the risks imposed by unfit drivers and pilots range from automatic safety systems to the use of a copilot trained to spot signs of unfitness. The risk of sudden cardiac event has long been a cause for concern although there are no quantitative data identifying the frequency of attributable transport accidents. For airline pilot fitness a risk of less than 1% of a fatal event in the subsequent year is considered acceptable in the presence of a copilot. The risk ceiling is 20% annually for car drivers and 2% for bus and lorry drivers. The risk of hypoglycaemia from diabletes is more complex to assess. Sight defects correctable by the use of glasses are not considered a problem but useful field of view should be checked. Other stable vision impairments may be assessed using practical driving tests under controlled conditions. The risks from variable impairments such as alcohol and fatigue are discussed. The development of common criteria across transport modes is considered.
Life prospects and quality of life in patients with Crohn's disease.
Authors: V Z Sorensen, B G Olsen, V Binder
Journal: Gut (1987)

A regional prevalence group of 106 patients with Crohn9s disease were interviewed about their familial, social, and professional conditions. The results were compared with results from similar interviews of an age and sex matched control group of 75 previously healthy patients admitted to the hospital for acute diseases of less than 28 days9 duration. An equal percentage of the patients and the controls were married (67% vs 71%) and had become parents (68% vs 79%). The number of children was slightly lower among Crohn9s disease patients. The occurrence of familial problems and sexual problems did not differ among patients and controls. The intake of sedatives was low in both groups and no difference was found in alcohol and tobacco intake between patients and controls. A combined score for social activities comprising cultural, sporting, educational and private social arrangements showed that about one-third of patients and controls had high social activity and about half of both groups had moderately high social activity. A similar physical activity score showed no difference between the two groups. The socioeconomic level of the Crohn9s disease patients was slightly, but significantly higher than that of the controls. Sixty five per cent of Crohn9s disease patients were employed, 64% of controls; 6% and 7% respectively unemployed. Three per cent of Crohn9s disease patients had disablement pension. Of Crohn9s disease patients employed, a higher percentage (77%) had remained in the same job for more than five years (64% of controls). The number of sick leave days during previous year was less than 11 in 72/69% of patients and controls. In spite of these objectively good results 54% of patients with Crohn9s disease felt exacerbations of their disease strained their professional and personal life. During the previous year 23% reported decreased working capacity and 21% reported decreased leisure activities, compared with their own expectations.
Tracheal Gas Insufflation
Authors: LESLIE A. HOFFMAN, ADELAIDA M. MIRO, FREDERICK J. TASOTA, EDGAR DELGADO, THOMAS G. ZULLO, JOHN LUTZ, MICHAEL R. PINSKY
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

In mechanically ventilated adults with acute respiratory distress syndrome (ARDS), peak airway pressures (Pawpeak) above 35 cm H2O may increase the risk of barotrauma or volutrauma. Tracheal gas insufflation (TGI), an adjunctive ventilatory technique, may facilitate a reduction in set inspiratory pressure in these patients, and thereby in the tidal volume (Vt) and Pawpeak used in their ventilation, without a consequent increase in arterial carbon dioxide tension (Paco 2). The purpose of this study was to: (1) assess the limits of efficacy of continuous TGI at two levels of decreased mechanical ventilatory support; and (2) determine an appropriate time interval after initiation of TGI at which to evaluate response. We prospectively studied eight adults with ARDS and increased airway pressures (40.2 ± 2.7 cm H2O) who were managed with pressure-control ventilation (PCV). After obtaining baseline ventilatory and hemodynamic measures, we initiated TGI at 10 L/min, adjusting ventilator positive-end expiratory pressure (PEEP) to maintain baseline Vt, and decreased the set inspiratory pressure by 5 cm H2O. Data were obtained after 30 and 60 min. Set inspiratory pressure was then decreased by an additional 5 cm H2O (total: 10 cm H2O), and data were again obtained after 30 min. Baseline (zero TGI) measures were then again recorded. Thirty minutes after decreasing the set inspiratory pressure by 5 cm H2O with TGI at 10 L/min, there was a 15% decrease in Pawpeak and a 16% decrease in Vt as compared with their baseline values. However, PaCO2 remained constant (59 ± 10 mm Hg versus 57 ± 6 mm Hg) (p = NS). There was no change in PaO2 or in hemodynamic variables, and no differences between variables, at 30 min versus 60 min in seven subjects. The remaining subject did not tolerate the reduction in set inspiratory pressure for 60 min. Thirty minutes after the set inspiratory pressure was decreased by 10 cm H2O with TGI at 10 L/min, there was a 26% decrease in Pawpeak and a 26% decrease in Vt. However, PaCO2 increased by 19% and PaO2 decreased by 13%. Six subjects completed this phase of the protocol for 30 min, and one subject completed it for 60 min. TGI can be used to rapidly facilitate a 5 cm H2O reduction in set inspiratory pressure without an increase in PaCO2 . The ability to achieve a 5 cm H2O reduction in set inspiratory pressure without adverse physiologic effects was evident within 30 min. Attempts to further reduce set inspiratory pressure were not successful.
Intracellular Dyssynchrony of Diastolic Cytosolic [Ca <sup>2+</sup> ] Decay in Ventricular Cardiomyocytes in Cardiac Remodeling and Human Heart Failure
Authors: Felix Hohendanner, Senka Ljubojević, Niall MacQuaide, Michael Sacherer, Simon Sedej, Liesbeth Biesmans, Paulina Wakula, Dieter Platzer, Sophie Sokolow, André Herchuelz, Gudrun Antoons, Karin Sipido, Burkert Pieske, Frank R. Heinzel
Journal: Circulation Research (2013)

Synchronized release of Ca²⁺ into the cytosol during each cardiac cycle determines cardiomyocyte contraction.
Circulating Vascular Progenitor Cells in Patients With Type 1 Diabetes and Microalbuminuria
Authors: Cecile Dessapt, Janaka Karalliedde, Maria Hernandez-Fuentes, Paz Prieto Martin, Giuseppe Maltese, Nikesh Dattani, Ravinder Atkar, GianCarlo Viberti, Luigi Gnudi
Journal: Diabetes Care (2010)

Patients with type 1 diabetes and microalbuminuria are at increased risk of cardiovascular disease (CVD). Abnormalities in vascular progenitor cells, which participate in vascular repair, may be implicated in this susceptibility.We studied the number and function of vascular progenitor cells in 22 type 1 diabetic patients with history of microalbuminuria (MA(+)) and 22 type 1 diabetic patients without history of microalbuminuria (MA(-)), of similar age, diabetes duration, glycemic control, renal function, and no history of CVD.MA(+) patients had lower circulating CD34(+) and CD34(+)/CD133(+) cell numbers compared with MA(-) patients (P < 0.006). In in vitro functional assays, MA(+) patients had a significantly lower number of colony-forming units and impaired vascular endothelial growth factor (VEGF)-A-mediated tube formation, when compared with MA(-) patients (P < 0.01).In type 1 diabetic patients with microalbuminuria, a marker of microvascular injury and a risk factor for CVD, circulating vascular progenitor cell number is reduced and function is impaired.
Local cerebral blood volume response to carbon dioxide in man.
Authors: J H Greenberg, A Alavi, M Reivich, D Kuhl, B Uzzell
Journal: Circulation Research (1978)

We used an emission tomographic brain scanner to investigate the relationship between local cerebral blood volume (LCBV) and arterial blood carbon dioxide tension (PaCO2) in normal awake man. Measurements were made separately in three dimensions in various regions of grey and white matter, and the resting LCBV as well as the difference in sensitivity among these regions were compared. Over the range of PaCO2 studied (20-42 torr), the response of both the grey matter and the white matter to carbon dioxide was linear. The LCBV sensitivity of the grey matter to changes in PaCO2 was 0.053 ml/100 g per torr PaCO2 and in the white matter this sensitivity was 0.046 ml/100 g per torr PaCO2. These sensitivities were found not to be significantly different, yielding a slope of 0.049 ml/100 g per torr PaCO2 for the LCBV-PaCO2 curve for the entire brain. This is in excellent agreement with the other data for the whole brain. The resting cerebral blood volume of the grey matter at a PaCO2 of 34.4 torr, which was the average resting arterial carbon dioxide tension of the subjects, was 5.0 ml/100 g and was significantly higher than for white matter, which was 3.6 ml/100 g. At the local level, the cerebral blood volume of the frontal cortex is significantly less than that of the thalamus, whereas the frontoparietal cortex in the region of the sylvian fissure has a local cerebral blood volume significantly greater than that of the thalamus.
Secular Trends in Deaths From Cardiovascular Diseases
Authors: Yariv Gerber, Steven J. Jacobsen, Robert L. Frye, Susan A. Weston, Jill M. Killian, Véronique L. Roger
Journal: Circulation (2006)

Although age-adjusted cardiovascular disease (CVD) mortality has declined over the past decades, controversies remain about whether this trend was similar across locations of death and disease categories and about the existence of age and sex disparities.We examined CVD mortality trends in Olmsted County, Minnesota, between 1979 and 2003 using the categories defined by the American Heart Association, including coronary heart disease (CHD), non-CHD diseases of the heart, and noncardiac circulatory diseases. Data on demographics, cause, and location of death of all 6378 residents who died of CVD were analyzed. Although decreases in the age-adjusted rates occurred in all groups, the magnitude of the decline varied widely. Lesser annual declines were noted in out-of-hospital than in-hospital deaths (1.8% versus 4.8%; P<0.001), in older than in younger persons (1.5% at age > or =85 years versus 3.9% for those < or =74 years of age; P<0.001), and in women relative to men (2.5% versus 3.3%; P=0.007). Furthermore, although CHD showed a marked annual decrease (3.3%), more modest decrements were found for non-CHD diseases of the heart (2.1%) and noncardiac circulatory diseases (2.4%) (P=0.02 and P=0.04 for the comparison with CHD decline, respectively).Over the past 25 years, CVD mortality declined markedly in the community, but there were large disparities in the magnitude of the decline, resulting in a shift in the distribution toward out-of-hospital and non-CHD deaths. Further reduction in CVD mortality will require strategies directed at elderly persons and women, in whom out-of-hospital rates have improved only minimally.
Superior Activity of the Combination of Histone Deacetylase Inhibitor LAQ824 and the FLT-3 Kinase Inhibitor PKC412 against Human Acute Myelogenous Leukemia Cells with Mutant FLT-3
Authors: Purva Bali, Prince George, Pamela Cohen, Jianguo Tao, Fei Guo, Celia Sigua, Anasuya Vishvanath, Anna Scuto, Srinivas Annavarapu, Warren Fiskus, Lynn Moscinski, Peter Atadja, Kapil Bhalla
Journal: Clinical Cancer Research (2004)

Mutant FLT-3 receptor tyrosine kinase is a client protein of the molecular chaperone heat shock protein 90 and is commonly present and contributes to the leukemia phenotype in acute myelogenous leukemia (AML). LAQ824, a cinnamyl hydroxamate histone deacetylase inhibitor, is known to induce acetylation and inhibition of heat shock protein 90. Here, we determined the effects of LAQ824 and/or PKC412 (a FLT-3 kinase inhibitor) on the levels of mutant FLT-3 and its downstream signaling, as well as growth arrest and cell-death of cultured and primary human AML cells.The effect of LAQ824 and/or PKC412 treatment was determined on the levels of FLT-3 and phosphorylated (p)-FLT-3, on downstream pro-growth and pro-survival effectors, e.g., p-STAT5, p-AKT, and p-extracellular signal-regulated kinase (ERK) 1/2, and on the cell cycle status and apoptosis in the cultured MV4-11 and primary AML cells with mutant FLT-3.Treatment with LAQ824 promoted proteasomal degradation and attenuation of the levels of FLT-3 and p-FLT-3, associated with cell cycle G(1)-phase accumulation and apoptosis of MV4-11 cells. This was accompanied by attenuation of p-STAT5, p-AKT, and p-ERK1/2 levels. STAT-5 DNA-binding activity and the levels of c-Myc and oncostatin M were also down-regulated. Cotreatment with LAQ824 and PKC412 synergistically induced apoptosis of MV4-11 cells and induced more apoptosis of the primary AML cells expressing mutant FLT-3. This was also associated with more attenuation of p-FLT-3, p-AKT, p-ERK1/2, and p-STAT5.The combination of LAQ824 and PKC412 is highly active against human AML cells with mutant FLT-3, which merits in vivo studies of the combination against human AML.
Differential Selection of Genes of Cucumber Mosaic Virus Subgroups
Authors: B. Moury
Journal: Molecular Biology and Evolution (2004)

Cucumber mosaic virus (CMV) has an extremely broad plant-host range, a large number of vector species, and a wide geographical distribution. CMV is, therefore, a model by which to understand plant virus adaptation. The selective constraints exerted on the five proteins expressed from the CMV genome were evaluated by application of newly developed maximum-likelihood algorithms to analyze sequences available in data banks. The ratio between nonsynonymous and synonymous substitution rates (omega) was used to detect positive selection on particular codon sites. Amino acid sequences were conserved with omega ranging from 0.07 to 0.60 in different proteins. However, a small proportion of amino acids in proteins 1a, 2a, and 3b, the coat protein (CP), were positively selected (omega > 1). Moreover, the evolution of the CP in the three subgroups of CMV strains revealed different selection profiles along the sequence and significantly different speed of evolution at many positions. Constraints exerted by aphid transmission, rather than plant adaptation, seemed to be responsible for these patterns of evolution in the CP.
Pre-exposure prophylaxis is effective at preventing HIV in high risk gay men, study shows
Authors: Susan Mayor
Journal: BMJ (2015)

Daily HIV medicine is highly effective in preventing new HIV infections in gay men who are HIV negative but at high risk of becoming infected, a study has shown. The findings supported adding pre-exposure prophylaxis (PrEP) as soon as possible to HIV prevention measures in men who have sex with men who are at high risk of HIV infection, the researchers said.

The open label study enrolled 544 HIV negative men who have sex with men who had had anal intercourse without a condom in the previous 90 days. They were recruited from 13 sexual health clinics in England from November 2012 …
Complex Tumor Genomes Inferred from Single Circulating Tumor Cells by Array-CGH and Next-Generation Sequencing
Authors: Ellen Heitzer, Martina Auer, Christin Gasch, Martin Pichler, Peter Ulz, Eva Maria Hoffmann, Sigurd Lax, Julie Waldispuehl-Geigl, Oliver Mauermann, Carolin Lackner, Gerald Höfler, Florian Eisner, Heinz Sill, Hellmut Samonigg, Klaus Pantel, Sabine Riethdorf, Thomas Bauernhofer, Jochen B. Geigl, Michael R. Speicher
Journal: Cancer Research (2013)

Circulating tumor cells (CTC) released into blood from primary cancers and metastases reflect the current status of tumor genotypes, which are prone to changes. Here, we conducted the first comprehensive genomic profiling of CTCs using array-comparative genomic hybridization (CGH) and next-generation sequencing. We used the U.S. Food and Drug Administration-cleared CellSearch system, which detected CTCs in 21 of 37 patients (range, 1-202/7.5 mL sample) with stage IV colorectal carcinoma. In total, we were able to isolate 37 intact CTCs from six patients and identified in those multiple colorectal cancer-associated copy number changes, many of which were also present in the respective primary tumor. We then used massive parallel sequencing of a panel of 68 colorectal cancer-associated genes to compare the mutation spectrum in the primary tumors, metastases, and the corresponding CTCs from two of these patients. Mutations in known driver genes [e.g., adenomatous polyposis coli (APC), KRAS, or PIK3CA] found in the primary tumor and metastasis were also detected in corresponding CTCs. However, we also observed mutations exclusively in CTCs. To address whether these mutations were derived from a small subclone in the primary tumor or represented new variants of metastatic cells, we conducted additional deep sequencing of the primary tumor and metastasis and applied a customized statistical algorithm for analysis. We found that most mutations initially found only in CTCs were also present at subclonal level in the primary tumors and metastases from the same patient. This study paves the way to use CTCs as a liquid biopsy in patients with cancer, providing more effective options to monitor tumor genomes that are prone to change during progression, treatment, and relapse.