tbuckley/cabot-search huggingface dataset:
Effect of reduced aortic compliance on cardiac efficiency and contractile function of in situ canine left ventricle.
Authors: R P Kelly, R Tunin, D A Kass
Journal: Circulation Research (1992)

This study tests the hypothesis that arterial vascular stiffening adversely influences in situ left ventricular contractile function and energetic efficiency. Ten reflex-blocked anesthetized dogs underwent a bypass operation in which a Dacron graft was sewn to the ascending aorta and connected to the infrarenal abdominal aorta via a plastic conduit. Flow was directed through either native aorta or plastic conduit by placement of vascular clamps. Arterial properties were measured from aortic pressure-flow data, and ventricular function was assessed by pressure-volume (PV) relations. Coronary sinus blood was drained via an extracorporeal circuit for direct measurement of myocardial O2 consumption (MVO2). Data at multiple steady-state preload volumes were combined to derive chamber function and energetics relations. Energetic efficiency was assessed by the inverse slope of the MVO2-PV area relation. Directing flow through plastic versus native aorta resulted in a 60-80% reduction in compliance but little change in mean resistance. Arterial pulse pressure rose from 34 to 99 mm Hg (p less than 0.001). Contractile function assessed by the end-systolic PV relation, stroke work-end-diastolic volume relation, and dP/dtmax at matched end-diastolic volume did not significantly change. However, MVO2 increased by 32% (p less than 0.01) and was matched by a rise in PV area, such that the MVO2-PV area relation and efficiency was unaltered. The MVO2 required to sustain a given stroke volume, however, increased from 20% to 40%, depending on the baseline level (p less than 0.001). Thus, whereas the contractile function and efficiency of normal hearts are not altered by ejection into a stiff vascular system, the energetic cost to the heart for maintaining adequate flow is increased. This suggests a mechanism whereby human vascular stiffening may yield little functional decrement at rest but limit reserve capacity under conditions of increased demand.
MicroRNA-1298 is regulated by DNA methylation and affects vascular smooth muscle cell function by targeting connexin 43
Authors: Wei Hu, Mian Wang, Henghui Yin, Chen Yao, Qiong He, Leping Yin, Chunxiang Zhang, Wen Li, Guangqi Chang, Shenming Wang
Journal: Cardiovascular Research (2015)

Growing evidence links microRNA to the process of peripheral vascular disease. Recently, we have found that microRNA-1298(miR-1298) is one of the most significantly down-regulated microRNAs in human arteries with arteriosclerosis obliterans (ASO) of the lower extremities. However, little is known regarding its role in the process of ASO. The present study aimed to investigate the expression, regulatory mechanisms, and functions of miR-1298 in the process of ASO.Using quantitative reverse-transcription PCR and in situ hybridization assays, miR-1298 was observed predominantly expressed in the vascular smooth muscle cells (VSMCs) and was significantly down-regulated in ASO compared with normal arteries. Pyrosequencing analysis revealed that the miR-1298 DNA upstream of CpG sites were hypermethylated in ASO compared with normal arteries. Next, the luciferase reporter assay revealed that miR-1298 down-regulation is related with upstream DNA CpG site hypermethylation. Introducing a miR-1298 mimic into cultured VSMCs significantly attenuated cell proliferation and migration. Connexin 43 (Cx43) was validated to be a functional target of miR-1298 that was involved in the miR-1298-mediated cellular effects. Finally, lentivirus-mediated delivery of miR-1298 and its target Cx43 into a rat carotid balloon injury model indicated that re-overexpression of miR-1298 significantly decreased neointimal formation by targeting connexin 43.Our data demonstrate a specific role of the upstream DNA methylation/miR-1298/Cx43 pathway in regulating VSMC function and suggest that modulation of miR-1298 levels may offer a novel therapeutic approach for ASO.
Nongranulomatous interstitial lung disease in Crohn's disease
Authors: G Hotermans, A Benard, H Guenanen, G Demarcq-Delerue, T Malart, B Wallaert
Journal: European Respiratory Journal (1996)

Crohn's disease is a granulomatous systemic disorder of unknown aetiology. Obvious pulmonary involvement is exceptional. We report the case of a 33 year old woman treated with mesalazine for Crohn's disease and presenting with dyspnoea. Pulmonary function tests showed a restrictive ventilatory pattern with hypoxaemia on exertion. Chest radiography disclosed an interstitial pattern with ground glass on high resolution computer tomography. Clinical and radiological abnormalities progressed after withdrawal of mesalazine. Corticosteroids led to a partial regression but were stopped because of severe side-effects. Because of worsening of the clinical situation, open lung biopsy was performed and showed a histopathological aspect of nongranulomatous interstitial diffuse lung disease with an inflammatory lymphoid infiltration associated to some mild interstitial collagen fibrosis. Addition of cyclophosphamide to high-dose pulse steroid therapy induced a significant and sustained improvement.
Effect of inhaled thiorphan, a neutral endopeptidase inhibitor, on the bronchodilator response to inhaled atrial natriuretic peptide (ANP).
Authors: R. M. Angus, E. A. Millar, G. W. Chalmers, N. C. Thomson
Journal: Thorax (1996)

BACKGROUND: The hormone atrial natriuretic peptide (ANP) causes bronchodilation and partially protects against direct and indirect bronchial challenges. Both in vitro and in vivo studies have found that the protective effect of ANP against bronchoconstriction is enhanced by inhibition of the enzyme neutral endopeptidase (NEP). It was hypothesised that pretreatment with thiorphan, an NEP inhibitor, might enhance the bronchodilator response to inhaled ANP. METHODS: In a randomised double blind placebo controlled crossover study, six asthmatic patients (one woman) of mean (SD) age 47.3 (3.8) years and forced expiratory volume in one second (FEV1) 1.91 (0.42) 1, 55 (3.8)% predicted, were studied. All were shown at screening to have at least a 25% improvement in FEV1 to inhaled salbutamol. On five study visits the patients received either thiorphan 1 mg (in 2 ml) followed by ANP 5 mg or placebo (saline), or placebo (saline) followed by ANP (5 mg), placebo or salbutamol 5 mg. Spirometric parameters were measured after each inhalation and thereafter for the next two hours. RESULTS: ANP alone caused a bronchodilator response up to 15 minutes when compared with placebo or thiorphan alone with a mean (SE) change in FEV1 of 16.8 (8.1)% and 16.1 (6.8)% at 10 and 15 minutes from baseline, respectively. Prior inhalation of thiorphan prolonged the duration of the bronchodilator effect of ANP up to 60 minutes with a mean (SE) change in FEV1 of 23.1 (3.4)% at 60 minutes. There was no difference in the maximum degree of bronchodilation following the administration of ANP alone compared with the combination of thiorphan and ANP. The degree and duration of the bronchodilator response produced by ANP, or the combination of the NEP inhibitor and ANP, were less than that produced by salbutamol. CONCLUSIONS: These results confirm that, at least in part, the bronchodilator response to inhaled ANP is modulated by NEP. Analogues of ANP which are stable to NEP may have greater bronchodilator activity than ANP in the treatment of asthma.
Intensive Blood Pressure Treatment Does Not Improve Cardiovascular Outcomes in Centrally Obese Hypertensive Individuals With Diabetes
Authors: Joshua I. Barzilay, Annie G. Howard, Gregory W. Evans, Jerome L. Fleg, Robert M. Cohen, Gillian L. Booth, Angela R. Kimel, Carolyn F. Pedley, William C. Cushman
Journal: Diabetes Care (2012)

OBJECTIVE The Action to Control Cardiovascular Risk in Diabetes (ACCORD) Blood Pressure Trial reported no differences in most cardiovascular disease (CVD) outcomes between intensive and standard blood pressure therapy in individuals with diabetes mellitus (DM) and hypertension. Many such individuals are centrally obese. Here we evaluate whether the trial outcomes varied by the level of central obesity. RESEARCH DESIGN AND METHODS The cohort included 4,687 people (47.7% women) with DM and hypertension. Mean age was 62.2, and mean follow-up was 4.7 years. Participants were randomly assigned to one of two blood pressure treatment strategies: intensive (systolic &amp;lt;120 mmHg) or standard (systolic &amp;lt;140 mmHg). Sex-specific quartiles of waist-to-height ratio were used as the measure of central obesity. The primary ACCORD outcome (a composite of nonfatal myocardial infarction [MI], nonfatal stroke, or CVD death) and three secondary outcomes (nonfatal MI, fatal or nonfatal stroke, and CVD death) were examined using proportional hazard models. RESULTS There was no evidence that the effect of intensively lowering blood pressure differed by quartile of waist-to-height ratio for any of the four outcomes (P &amp;gt; 0.25 in all cases). Controlling for waist-to-height quartile had no significant impact on previously published results for intensive blood pressure therapy. Waist-to-height ratio was significantly related to CVD mortality (hazard ratio 2.32 [95% CI 1.40–3.83], P = 0.0009 comparing the heaviest to lightest quartiles), but not to the other outcomes (P &amp;gt; 0.09 in all cases). CONCLUSIONS Intensive lowering of blood pressure versus standard treatment does not ameliorate CVD risk in individuals with DM and hypertension. These results did not vary by quartile of waist-to-height ratio.
Linear System for Quantitating Hydrogen at a Platinum Electrode
Authors: EDWARD S. HYMAN
Journal: Circulation Research (1961)

With a low impedance, transistor measuring circuit, the response of a platinum-platinum black electrode to hydrogen in solution is found to be linear with concentration. Hydrogen in solution can he qnantitated by this circuit. This offers the possibility of quanti tation of hydrogen by an intravascular plati num electrode. It may now be possible to quantitate, as well as detect, intracardiac shunts and repeat the observation without the withdrawal of blood.
Risk score for predicting death, myocardial infarction, and stroke in patients with stable angina, based on a large randomised trial cohort of patients
Authors: Tim C Clayton, Jacobus Lubsen, Stuart J Pocock, Zoltán Vokó, Bridget-Anne Kirwan, Keith A A Fox, Philip A Poole-Wilson
Journal: BMJ (2005)

Objective To derive a risk score for the combination of death from all causes, myocardial infarction, and disabling stroke in patients with stable symptomatic angina who require treatment for angina and have preserved left ventricular function. Design Multivariate Cox regression analysis of data from a large multicentre trial. Setting Outpatient cardiology clinics in western Europe, Israel, Canada, Australia, and New Zealand. Participants 7311 patients with all required data available. Main outcome measure Death from any cause or myocardial infarction or disabling stroke during a mean follow-up of 4.9 years. Results 1063 patients either died from any cause or sustained myocardial infarction or disabling stroke. The five year risk of this composite ranged from 4% for patients in the lowest tenth of risk to 35% for patients in the highest tenth. The risk score combines 16 routinely available clinical variables (in order of decreasing contribution): age, left ventricular ejection fraction, smoking, white blood cell count, diabetes, casual blood glucose concentration, creatinine concentration, previous stroke, at least one angina attack a week, coronary angiographic findings (if available), lipid lowering treatment, QT interval, systolic blood pressure ≥ 155 mm Hg, number of drugs used for angina, previous myocardial infarction, and sex. Fitting the same model separately to all cause death, myocardial infarction, and stroke gave similar results. The risk score did not seem to predict the nature of the event (death in 39%, myocardial infarction in 46%, and disabling stroke in 15%) or the incidence of angiography or revascularisation, which occurred in 29% of patients. Conclusion This risk score is an objective aid in deciding on further management of patients with stable angina with the aim of reducing serious outcome events. The score can also be used in planning future trials.
Noncationic Peptides Obtained From Azurin Preferentially Enter Cancer Cells
Authors: Brad N. Taylor, Rajeshwari R. Mehta, Tohru Yamada, Fatima Lekmine, Konstantin Christov, Ananda M. Chakrabarty, Albert Green, Laura Bratescu, Anne Shilkaitis, Craig W. Beattie, Tapas K. Das Gupta
Journal: Cancer Research (2009)

Abstract Azurin, a member of the cupredoxin family of copper containing redox proteins, preferentially penetrates human cancer cells and exerts cytostatic and cytotoxic (apoptotic) effects with no apparent activity on normal cells. Amino acids 50 to 77 (p28) of azurin seem responsible for cellular penetration and at least part of the antiproliferative, proapoptotic activity of azurin against a number of solid tumor cell lines. We show by confocal microscopy and fluorescence-activated cell sorting that amino acids 50 to 67 (p18) are a minimal motif (protein transduction domain) responsible for the preferential entry of azurin into human cancer cells. A combination of inhibitors that interfere with discrete steps of the endocytotic process and antibodies for caveolae and Golgi-mediated transport revealed that these amphipathic, α-helical peptides are unique. Unlike the cationic cell-penetrating peptides, α-helical antennapedia-like, or VP22 type peptides, p18 and p28 are not bound by cell membrane glycosaminoglycans and preferentially penetrate cancer cells via endocytotic, caveosome-directed, and caveosome-independent pathways. Once internalized, p28, but not p18, inhibits cancer cell proliferation initially through a cytostatic mechanism. These observations suggest the azurin fragments, p18 and p28, account for the preferential entry of azurin into human cancer cells and a significant amount of the antiproliferative activity of azurin on human cancer cells, respectively. [Cancer Res 2009;69(2):537–46]
Evidence-Based Prescribing of Statins: A Developing World Perspective
Authors: H. T Ong
Journal: PLoS Medicine (2006)

ver the last decade, landmark clinical trials (summarized in Tables 1 and 2) have shown that statin therapy reduces coronary events in patients with or without prior cardiovascular disease [1–12]. More recent studies, summarized in Table 3, show that the larger the statin dosage, the greater the reduction in cardiovascular clinical events [13–17]. A meta-analysis involving 90,056 patients in 14 randomized trials emphasizes that the beneﬁ t of statin treatment is not limited to a reduction in coronary disease; treatment also reduces the incidence of strokes, coronary revascularization, and coronary and total mortality [18].But statins are expensive, and clinicians and policymakers must objectively review the literature so that statin therapy can be appropriately initiated and be cost effective. In developing countries, where a changing lifestyle is increasing the incidence of cardiovascular disease, the need to be cost effective is even more pressing. This paper attempts to derive a fair and evidence-based answer to four practical questions that are especially relevant in less wealthy societies: (1) In whom and when should statin therapy be initiated? (2) What lipid level should physicians aim for? (3) Do different ethnic groups respond differently to statins? and (4) Are statins cost effective?
ELECTROPHORESIS OF THE COMPLEMENT-FIXING ANTIGEN OF HUMAN INFLUENZA VIRUS
Authors: Jaques Bourdillon, Edwin H. Lennette
Journal: The Journal of Experimental Medicine (1940)

1. An electrophoretic study has been made of normal mouse serum, influenza mouse serum, and influenza mouse lung suspension. The mobilities of the protein fractions present have been determined at various pH's by the optical method. 2. The pH-mobility curve of the soluble (complement-fixing) antigen present in the lung suspension has been determined analytically by sampling and application of the complement fixation test. The results show that the complement-fixing antigen has a mobility definitely smaller than that of serum albumin and close to that of a globulin, with an isoelectric point close to pH 5.
Loss of cardioprotection with ageing
Authors: K. Boengler, R. Schulz, G. Heusch
Journal: Cardiovascular Research (2009)

Not only the prevalence, but also the mortality due to ischaemic cardiovascular disease is higher in older than in young humans, and the demographic shift towards an ageing population will further increase the prevalence of age-related cardiovascular disease. In order to develop strategies aimed to limit reversible and irreversible myocardial damage in older patients, there is a need to better understand age-induced alterations in protein expression and cell signalling. Cardioprotective phenomena such as ischaemic and pharmacological pre and postconditioning attenuate ischaemia/reperfusion injury in young hearts. Whether or not pre and postconditioning are still effective in aged organs, animals, or patients, i.e. under conditions where such cardioprotection is most relevant, is still a matter of debate; most studies suggest a loss of protection in aged hearts.
Treatment of cutaneous sarcoid with topical gel psoralen and ultraviolet A
Authors: C.M. Gleeson, N. Morar, I. Staveley, C.B. Bunker
Journal: British Journal of Dermatology (2010)

Journal Article Treatment of cutaneous sarcoid with topical gel psoralen and ultraviolet A Get access C.M. Gleeson, C.M. Gleeson Department of Dermatology, Chelsea and Westminster NHS Foundation Trust, 369 Fulham Road, London SW10 9NH, U.K. E‐mail: cgleeson@doctors.org.uk Search for other works by this author on: Oxford Academic Google Scholar N. Morar, N. Morar Department of Dermatology, Chelsea and Westminster NHS Foundation Trust, 369 Fulham Road, London SW10 9NH, U.K. E‐mail: cgleeson@doctors.org.uk Search for other works by this author on: Oxford Academic Google Scholar I. Staveley, I. Staveley Department of Dermatology, Chelsea and Westminster NHS Foundation Trust, 369 Fulham Road, London SW10 9NH, U.K. E‐mail: cgleeson@doctors.org.uk Search for other works by this author on: Oxford Academic Google Scholar C.B. Bunker C.B. Bunker Department of Dermatology, Chelsea and Westminster NHS Foundation Trust, 369 Fulham Road, London SW10 9NH, U.K. E‐mail: cgleeson@doctors.org.uk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 164, Issue 4, 1 April 2011, Pages 892–894, https://doi.org/10.1111/j.1365-2133.2010.10175.x Published: 01 April 2011
Syk Tyrosine Kinase Is Linked to Cell Motility and Progression in Squamous Cell Carcinomas of the Head and Neck
Authors: Sutima Luangdilok, Carol Box, Lisa Patterson, William Court, Kevin Harrington, Lisa Pitkin, Peter Rhŷs-Evans, Pornchai O-charoenrat, Suzanne Eccles
Journal: Cancer Research (2007)

Abstract Syk, a non–receptor tyrosine kinase, is an important component of immunoreceptor signaling in hematopoietic cells. It has been implicated in key regulatory pathways including phosphoinositide 3-kinase and phospholipase Cγ (PLCγ) activation in B cells and integrin signaling in platelets and bronchial epithelial cells. Recently, potential roles in cancer have been reported. In breast cancers, reduced Syk expression was associated with invasion, and its overexpression in cell lines was shown to inhibit cell motility. In contrast, Syk has been shown to mediate chemomigration in nasopharyngeal carcinoma cells. Its role in squamous cell carcinomas of the head and neck (SCCHN) has not yet been investigated. Syk mRNA and protein expression was detected in 6 of 10 SCCHN cell lines. When Syk was transfected into Syk-negative cells (SIHN-011A), chemomigration was enhanced in vitro and this was associated with activation of PLCγ1. Conversely, abrogation of Syk activity by pharmacologic inhibition or small interfering RNA in HN6 cells with high levels of endogenous expression inhibited migration, haptotaxis, and engagement with matrix proteins; this was accompanied by decreased levels of phosphorylated AKT. Similar effects were seen in Syk-positive CAL 27 cells but not in Syk-negative SIHN-011A cells. Immunoprecipitation suggested co-association of Syk with epidermal growth factor receptor and GRB-2. Syk expression in SCCHN patient tissues was examined by semiquantitative real-time PCR (n = 45) and immunohistochemistry (n = 38) in two independent cohorts. Higher levels of Syk expression were observed in tumors and lymph node metastases relative to normal tissues. High Syk expression significantly correlated with worse survival and may be of prognostic value in SCCHN due to its potential role in cell migration and invasion. [Cancer Res 2007;67(16):7907–16]
Introduction of Francis S. Collins
Authors: David Ginsburg
Journal: Journal of Clinical Investigation (2015)

Francis Sellers Collins was born in Staunton, Virginia, on April 14, 1950, with his family pedigree shown in Figure 1A. His parents, Margaret and Fletcher, met as graduate students at Yale — his mother in English and his father in drama. They settled in Staunton, Virginia, in 1946, where Fletcher taught theater at Mary Baldwin College and Margaret wrote plays. They spent the rest of their very full lives in Staunton, both living to the age of 98 and married for 73 years. Fletcher and Margaret’s home was a center for music and theater culture in Staunton, including serving as the site for their Annual Twelfth Night Music party, which was attended by major folk music figures each year and in which Francis would also reliably participate. Francis is the youngest of four brothers (Figure 1B) and was home-schooled until he was 10. He then attended Robert E. Lee High School, graduating at the age of 16 (Figure 2) and moving on to the University of Virginia, where he graduated in 1970 with a BS in Chemistry. Figure 3 shows Francis with his college band, the last known picture of him without a mustache.
The changing epidemiology of Staphylococcus aureus bloodstream infection: a multinational population-based surveillance study
Authors: K.B. Laupland, O. Lyytikäinen, M. Sgaard, K.J. Kennedy, J.D. Knudsen, C. Ostergaard, J.C. Galbraith, L. Valiquette, G. Jacobsson, P. Collignon, H.C. Schnheyder
Journal: Clinical Microbiology and Infection (2012)
LETTER-SIWE DISEASE REPORT OF SIX CASE
Authors: D. BURROWS, A. M. T. KELLY, J. M. BRIDGES, J. H. CONNOLLY
Journal: British Journal of Dermatology (1970)

SUMMARY.— Six cases of Letterer-Siwe disease occurring in a population of 1,500,000 over a period of 10 years are described. Five have died and 1 survives 2 years after cessation of therapy and 4 years after diagnosis. Of those who died, in 2 the terminal event was measles infection, in 1 surgical emphysema consequent on rupture of a lung cyst and in 2 death followed progression of the disease.