tbuckley/cabot-search huggingface dataset:
Repression of Choroidal Neovascularization Through Actin Cytoskeleton Pathways by MicroRNA-24
Authors: Qinbo Zhou, Chastain Anderson, Hongmei Zhang, Xinyu Li, Fiona Inglis, Ashwath Jayagopal, Shusheng Wang
Journal: Molecular Therapy (2013)

Actin cytoskeleton is critical for cell motility and division, both of which are important for angiogenesis. MicroRNAs (miRNA/miR) are emerging as pivotal modulators of vascular development and disease. How miRNAs regulate actin cytoskeleton dynamics in endothelial cells (EC) and neovascularization is still unclear. Here, we report that miR-24 regulates actin dynamics in ECs through targeting multiple members downstream of Rho signaling, including Pak4, Limk2, and Diaph1 proteins. Overexpression of miR-24 in ECs blocks stress fiber and lamellipodia formation, represses EC migration, proliferation, and tube formation in vitro, as well as angiogenesis in an ex vivo aortic ring assay. Moreover, subretinal delivery of miR-24 mimics represses laser-induced choroidal neovascularization (CNV) in vivo. Mechanistically, knockdown of miR-24 target protein LIMK2 or PAK4 inhibits stress fiber formation and tube formation in vitro, mimicking miR-24 overexpression phenotype in angiogenesis, while overexpression of LIMK2 and PAK4 by adenoviruses partially rescued the tube formation defects in miR-24 overexpressing ECs. Taken together, these findings suggest that miR-24 represses angiogenesis by simultaneously regulating multiple components in the actin cytoskeleton pathways. Manipulation of actin cytoskeleton pathways by miR-24 may represent an attractive therapeutic solution for the treatment of wet age-related macular degeneration (AMD) and other vascular diseases.
PHYSICAL AND BIOLOGICAL PROPERTIES OF INFLUENZA VIRUS COMPONENTS OBTAINED AFTER ETHER TREATMENT
Authors: Fred M. Davenport, Rudolf Rott, Werner Schäfer
Journal: The Journal of Experimental Medicine (1960)

The Rostock strain of fowl plague, the swine, A, A', and Asian strains of influenza A as well as their hemagglutinin and internal s antigen subunits obtained after ether splitting, were found to be morphologically indistinguishable when examined simultaneously. Hemagglutinin fractions reacted in a highly strain specific manner when tested by hemagglutination inhibition or by complement fixation using sera obtained after infection. With the same sera internal s antigen fractions were shown to be serologically distinguishable by complement fixation. This observation may stimulate interest in the feasibility of employing immunologic techniques for the study of nucleoproteins. The significance of the findings reported is discussed.
Association Between Pulmonary Mycobacterium Avium Complex Infection and Lung Cancer
Authors: Leah Lande, Donald D. Peterson, Radhika Gogoi, Gary Daum, Kate Stampler, Rebecca Kwait, Christine Yankowski, Kate Hauler, Joshua Danley, Kristen Sawicki, Janet Sawicki
Journal: Journal of Thoracic Oncology (2012)
Clinical Aspects of Acetylcholine--I
Authors: F. R. Fraser
Journal: BMJ (1938)

I Physiology of AcetylcholineThe brilliant researches by Loewi and Dale and their co-workers since 1921 have built up step by step a firm slructure upon which rests the belief that acetylcholine transmits the effects of nervous impulses from the nerve endings to the organs throughout a large part of the body.It is not necessary for the purpose of these lectures to review this evidence, for a number of able, exhaustive, and critical accounts have been published recently (Loewi,
Small-cell carcinocythaemia.
Authors: P J Thompson, P Maloney, J Hewson
Journal: Thorax (1982)

<h3>Background</h3> Pharmaceutical care(PC) is the responsible provision of drug therapy for the purpose of achieving definite outcomes that improve a patient9s quality of life. <h3>Purpose</h3> To analyse the results of a PC program in patients who are infected with the virus of hepatitis C(HCV). <h3>Materials and Methods</h3> Period of study: April 2007-October 2011. It was aimed to prevent, detect and resolve medication-related problems (MRPs) in HCV patients. Phases: First visit: Prescription validation, medical history revision and elaboration of patient medical record. The authors inform patients about adverse reactions, interactions and healthy lifestyle habits. The authors stress the importance of treatment compliance in order to obtain a sustained viral response and how to minimise the side effects. Subsequent visits: Personalised monitoring, detection of MRPs and Pharmaceutical Intervention (PI). The authors establish visiting hours and evaluate the adherence to the pharmacotheraphy. The adherence calculation is done through dispensing registers. The adherent patient endorses the rule 80/80/80:80% of interferon (IFN), ribavirin (RBV) doses and 80% of the treatment time in relation to the genotype. <h3>Results</h3> 542 interviews were done in 365 patients under IFN and RBV treatment: oral information 67.16% and both oral and written 32.84%. Face to face interviews 90.22% and telephone ones 9.41%. 27.86% to start the treatment, 69.74% during the treatment, 0.55% by treatment change, 1.66% possible interaction and others 0.18%. Counselling reasons (227), the most frequent were: tiredness 15.86%, mental disorders 11,89%, reaction at the injection site 8.81%, gastrointestinal discomfort 8.81%, pseudo-flu syndrome 8.37%, insomnia 6.61% and pruritus 6.61%. 536 PI were accepted, with recommendations about healthy lifestyle habits and some pieces of advice on medication administration and handling side effects. In 45 times, patients were referred to the specialist doctor. <h3>Conclusions</h3> The majority of the patients applied for PC during the pharmacotheraphy follow-up, above all, by side effects related to medication. The interviews with the patients reinforce the information on their pharmacotheraphy in order to minimise side effects and resolve MRPs. The PC program in HCV patients helps to improve the safe use of medications and avoids unnecessary visits to the specialist doctor.
Antagonism of peripheral hepatic cannabinoid receptor-1 improves liver lipid metabolism in mice: Evidence from cultured explants
Authors: Tony Jourdan, Laurent Demizieux, Joseph Gresti, Louiza Djaouti, Lila Gaba, Bruno Vergès, Pascal Degrace
Journal: Hepatology (2011)

It is well established that inactivation of the central endocannabinoid system (ECS) through antagonism of cannabinoid receptor 1 (CB1R) reduces food intake and improves several pathological features associated with obesity, such as dyslipidemia and liver steatosis. Nevertheless, recent data indicate that inactivation of peripheral CB1R could also be directly involved in the control of lipid metabolism independently of central CB1R. To further investigate this notion, we tested the direct effect of the specific CB1R antagonist, SR141716, on hepatic carbohydrate and lipid metabolism using cultured liver slices. CB1R messenger RNA expression was strongly decreased by SR141716, whereas it was increased by the CB1R agonist, arachidonic acid N-hydroxyethylamide (AEA), indicating the effectiveness of treatments in modulating ECS activity in liver explants both from lean or ob/ob mice. The measurement of O(2) consumption revealed that SR141716 increased carbohydrate or fatty acid utilization, according to the cellular hormonal environment. In line with this, SR141716 stimulated ß-oxidation activity, and the role of CB1R in regulating this pathway was particularly emphasized when ECS was hyperactivated by AEA and in ob/ob tissue. SR141716 also improved carbohydrate and lipid metabolism, blunting the AEA-induced increase in gene expression of proteins related to lipogenesis. In addition, we showed that SR141716 induced cholesterol de novo synthesis and high-density lipoprotein uptake, revealing a relationship between CB1R and cholesterol metabolism.These data suggest that blocking hepatic CB1R improves both carbohydrate and lipid metabolism and confirm that peripheral CB1R should be considered as a promising target to reduce cardiometabolic risk in obesity.
Echocardiography in chronic aortic insufficiency. Is valve replacement too late when left ventricular end-systolic dimension reaches 55 mm?
Authors: P Fioretti, J Roelandt, R J Bos, R S Meltzer, D van Hoogenhuijze, P W Serruys, J Nauta, P G Hugenholtz
Journal: Circulation (1983)

To determine whether a ventricular (LV) end-systolic dimension (ESD) greater than or equal to 55 mm and LV left fractional shortening less than 25% are risk factors for aortic valve replacement (AVR) in patients with aortic insufficiency, we analyzed the clinical course and M-mode echocardiograms in 47 consecutive patients who underwent AVR for isolated symptomatic AI. Group 1 patients (n = 27) had a preoperative ESD less than 55 mm (mean 44 mm, range 30-52 mm) and group 2 patients (n = 20) had a preoperative ESD greater than or equal to 55 mm (mean 62 mm, range 55-85 mm). One patient in group 1 and 10 patients in group 2 had left ventricular fractional shortening less than 25%. There were no perioperative or postoperative deaths during an average follow-up of 41 months (range 6-76 months). Five patients had perioperative myocardial infarctions (MIs), three in group 1 and two in group 2. Since myocardial protection with cold potassium cardioplegia was instituted, no patient has suffered a perioperative MI. The average preoperative New York Heart Association functional classification was 2.3 (group 1) and 2.6 (group 2). Postoperatively, it was 1.2 in group 1 and 1.1 in group 2. Thirty-three patients (20 in group 1 and 13 in group 2) had echocardiograms at least 1 year after AVR. Of these, LV-end diastolic dimension decreased fro 67 +/- 6 to 53 +/- 6 mm (mean +/- SD) in group 1 (p less than 0.001) and from 79 +/- 3 to 55 +/- 6 mm in group 2 (p less than 0.001). The LVESD also decreased, but this is difficult to interpret because of frequent postoperative abnormal interventricular septal motion. The LV cross-sectional area, an index of LV mass, decreased in group 1 from 25 +/- 5 to 20 +/- 5 cm2 (p lss than 0.001) and in group 2 from 32 +/- 9 to 20 +/- 5 cm2 (p less than 0.001). Postoperative end-diastolic dimension and cross-sectional area were not significantly different between the two groups. We concluded that in aortic insufficiency, a preoperative ESD greater than or equal to 55 mm does not preclude successful AVR, as judged by long-term survival, symptomatic relief, and normalization of LV dimensions assessed by echocardiography.
Incidence of Chlorthalidone-Induced Hypercalcemia
Authors: Fred J. Palmer
Journal: JAMA (1978)

<h3>To the Editor.—</h3> In 1974 a case of hypercalcemia secondary to the administration of chlorthalidone was reported (229:267, 1974). At that time the frequency of this phenomenon was unknown. To answer this question, 39 consecutive patients with untreated hypertension were placed on chlorthalidone therapy, 50 mg/ day. Each patient had baseline serum calcium levels determined before the administration of the drug and again four weeks after beginning therapy. None of the patients were taking any medications prior to the institution of therapy, and all patients had normal baseline serum calcium levels. All of the patients had normal renal function as determined by BUN and creatinine determinations. Twenty of the patients were women and 19 were men. The mean serum calcium level for the group prior to chlorthalidone administration was 9.7 mg/dl. After four weeks of the drug therapy, the mean serum calcium level was 10.0 mg/dl. Thirty (77%) of the
What's Keeping Us So Busy in Primary Care? A Snapshot from One Practice
Authors: Richard J. Baron
Journal: New England Journal of Medicine (2010)

A physician describes the daily work in his primary care practice and documents the high volume of tasks involved in patient care aside from face-to-face visits. In a typical day, each doctor saw 18 patients, made 24 telephone calls, sent 17 e-mail messages, and reviewed 31 laboratory and imaging reports and 14 consultation reports.
Diabetes Complications in NIDDM Kindreds Linked to the MODY3 Locus on Chromosome 12q
Authors: Gilberto Velho, Martine Vaxillaire, Valérie Boccio, Guillaume Charpentier, Philippe Froguel
Journal: Diabetes Care (1996)

To assess the prevalence of diabetes complications and the severity of diabetes in kindreds with NIDDM linked to the MODY3 locus (chromosome 12q) and to compare these parameters with data obtained in glucokinase (GCK)-deficient and other-MODY (unlinked to any of the three known loci) families, as well as with data from families with a late age of onset of NIDDM.Clinical and biological data were obtained from 667 affected members of 7 MODY3, 25 GCK-deficient, 6 other-MODY, and 81 NIDDM families. Severity of diabetes (glucose tolerance status and insulin secretion) was assessed by an oral glucose tolerance test. Neurological examination and eye fundus examination were performed in 349 and 251 subjects, respectively, and proteinuria was tested with strips in 282 family members.A higher prevalence of proliferative retinopathy was observed in MODY3 (21%) and NIDDM subjects (23%) than in GCK-deficient (3%) and other-MODY subjects (8%; P = 0.004). Proteinuria was detected in 19, 7, 5, and 0% (P = 0.07) of subjects, respectively. Prevalence of neuropathy was higher in NIDDM (17%; P = 0.005) than in MODY3 (4%), GCK-deficient (5%) and other-MODY (0%) subjects. MODY3 and NIDDM subjects had significantly higher fasting glucose levels than subjects in the other groups. Glucose levels after 2 h were significantly higher, and the ratios of insulin to glucose levels were significantly lower in MODY3 subjects than in the other three groups.The MODY3 subtype of NIDDM is characterized by a severe insulin secretory defect and by major hyperglycemia that progresses rapidly to overt diabetes. Microvascular complications of diabetes were frequently observed in the MODY3 subjects and the subjects with a late age of onset of NIDDM in this cohort. Both the duration and the severity of diabetes were independently associated with these complications.
Arrhythmias in patients with mitral valve prolapse.
Authors: R A Winkle, M G Lopes, J W Fitzgerald, D J Goodman, J S Schroeder, D C Harrison
Journal: Circulation (1975)

Resting ECGs, exercise treadmill tests and 24-hour ambulatory ECGs were recorded and analyzed in 24 unselected patients with mitral valve prolapse. Arrhythmias were frequent. There were three distinct groups of patients, defined on the basis of total number of premature ventricular contractions (PVCs) during the 24 hours; there were no PVCs in 25%, and frequent PVCs in 50%. Complex ventricular arrhythmias, including ventricular tachycardia in five patients, were found almost exclusively in the group with frequent PVCs. Fifteen of the 24 patients demonstrated atrial premature contractions (APCs) during the 24 hours. Complex atrial arrhythmias were found among patients with infrequent, as well as those with frequent, APCs. Supraventricular tachycardia was detected in seven of these patients. The incidence of ACPs decreased during sleep in 67% of the patients and showed no change during sleep in 33%. A poor correlation was found between symptoms recorded in patient diaries and changes noted on 24-hour ECG recordings. The peak PVCs/15 min and peak ACPs/15 min during a 24-hour period of monitoring was found to be an excellent guide to the total number of PVCs and APCs occurring during that period. This permits an accurate prediction of the total number of PVCs in 24 hours after performing an exact PVC count on only 15 minutes of ECG data. Finally, the 24-hour ambulatory ECG was sensitive than the treadmill test and both were superior to the 12-lead ECG for detecting arrhythmias in these patients.
Schistosomal colonic disease.
Authors: A R Mohamed, M al Karawi, M I Yasawy
Journal: Gut (1990)

This study evaluates 216 patients with schistosomal colonic disease, diagnosed by endoscopic biopsies at the Armed Forces Hospital, Riyadh. The colonoscopic appearance was suggestive of schistosomiasis in 98 of these patients (45.37%), Schistosoma mansoni ova in stool was detected in only 24 of these 216 patients (11.11%). The most common histopathological finding in colonic biopsies of these patients was Schistosoma mansoni ova in the colonic mucosa with no or mild inflammatory cells infiltrates. These findings correlate with the endoscopic appearances in most patients. The most common symptoms were abdominal pain or distention in 84 patients (38.88%). Sixty five patients (30.09%) had hepatosplenic schistosomiasis. Eight patients had schistosomal polyps and two patients had colonic malignancy in which no association between their malignancy and Schistosoma mansoni infection was established. After antischistosomal treatment follow up, sigmoidoscopy was normal in 28 patients who previously had abnormal endoscopic appearances. Colonoscopic examination is valuable in colonic schistosomiasis as it can show characteristic colonic lesions and colonic biopsies are diagnostic and correlates with histological findings.
Protective efficacy of a whole cell pertussis vaccine
Authors: M. Blennow, P. Olin, M. Granstrom, R. H Bernier
Journal: BMJ (1988)

A trial of the efficacy of a plain whole cell pertussis vaccine was conducted in Sweden. In this non-blinded trial 525 infants aged 2 months who were born on days with an even number received three doses of vaccine one month apart and 615 infants of the same age who were born on days with an odd number were enrolled as controls. During the 18 months of follow up there were 55 cases of pertussis. The attack rate was 1·5% (8/525) among the vaccinated children and 7·6% (47/615) among the unvaccinated children (p&lt;0·001). The estimated efficacy of the vaccine was 80% (95% confidence interval 58 to 90). The estimated efficacy of pertussis vaccine was similar to that observed in British trials over 30 years ago.
Healing of diabetic neuropathic foot ulcers receiving standard treatment. A meta-analysis.
Authors: D J Margolis, J Kantor, J A Berlin
Journal: Diabetes Care (1999)

The aim of the study was to determine the percentage of individuals with neuropathic diabetic foot ulcers receiving good wound care who heal within a defined period of time.We conducted a systematic review of the control groups of clinical trials that evaluated a treatment for diabetic neuropathic foot ulcers. The meta-analytic techniques used include an estimation of the weighted mean percentage healed by end point, an evaluation of the homogeneity of trials, and an estimate of the 95% CI of the grouped data. Grouped-data univariate and multivariate logistic regression was conducted to assess the impact of mean age, ulcer size, and duration on the percentage of ulcers healed at end point.We found a total of 10 control groups meeting our criteria. Six control groups used 20 weeks as the end point for healing or nonhealing. For the six control arms with a 20-week end point, we found a weighted mean healing rate of 30.9% (95% CI 26.6-35.1). A similar analysis for the four 12-week arms found a mean healing rate of 24.2% (19.5-28.8). We failed to detect any statistically significant heterogeneity for either the 20-week or the 12-week trials.After 20 weeks of good wound care, approximately 31% of diabetic neuropathic ulcers heal. Similarly, after 12 weeks of good care, approximately 24% of neuropathic ulcers attain complete healing. Further patient-level analyses are necessary to definitively determine the associations of age, wound size, and wound duration with likelihood of healing.
Stat5 activation enables erythropoiesis in the absence of EpoR and Jak2
Authors: Florian Grebien, Marc A. Kerenyi, Boris Kovacic, Thomas Kolbe, Verena Becker, Helmut Dolznig, Klaus Pfeffer, Ursula Klingmüller, Mathias Müller, Hartmut Beug, Ernst W. Müllner, Richard Moriggl
Journal: Blood (2008)
Hypoxia Induces Myocardial Regeneration in Zebrafish
Authors: Chris Jopling, Guillermo Suñé, Adèle Faucherre, Carme Fabregat, Juan Carlos Izpisua Belmonte
Journal: Circulation (2012)

Hypoxia plays an important role in many biological/pathological processes. In particular, hypoxia is associated with cardiac ischemia. which, although initially inducing a protective response, will ultimately lead to the death of cardiomyocytes and loss of tissue, severely affecting cardiac functionality. Although myocardial damage/loss remains an insurmountable problem for adult mammals, the same is not true for adult zebrafish, which are able to completely regenerate their heart after extensive injury. Myocardial regeneration in zebrafish involves the dedifferentiation and proliferation of cardiomyocytes to replace the damaged/missing tissue; at present, however, little is known about what factors regulate this process.We surmised that ventricular amputation would lead to hypoxia induction in the myocardium of zebrafish and that this may play a role in regulating the regeneration of the missing cardiac tissue. Using a combination of O(2) perturbation, conditional transgenics, in vitro cell culture, and microarray analysis, we found that hypoxia induces cardiomyocytes to dedifferentiate and proliferate during heart regeneration in zebrafish and have identified a number of genes that could play a role in this process.These results indicate that hypoxia plays a positive role during heart regeneration, which should be taken into account in future strategies aimed at inducing heart regeneration in humans.
Importance of Hemodynamic Factors in the Prognosis of Symptomatic Carotid Occlusion
Authors: Robert L. Grubb, Jr
Journal: JAMA (1998)

Context.-The relative importance of hemodynamic factors in the pathogenesis and treatment of stroke in patients with carotid artery occlusion remains controversial.Objective.-Totest the hypothesis that stage II cerebral hemodynamic failure (increased oxygen extraction measured by positron emission tomography [PET]) distal to symptomatic carotid artery occlusion is an independent risk factor for subsequent stroke in medically treated patients.Design and Setting.-Prospective,blinded, longitudinal cohort study of patients referred from a group of regional hospitals between 1992 and 1996.Patients.-From419 subjects referred, 81 with previous stroke or transient ischemic attack in the territory of an occluded carotid artery were enrolled.All were followed up to completion of the study, with average follow-up of 31.5 months.Main Outcome Measures.-Telephonecontact every 6 months recorded the subsequent occurrence of all stroke, ipsilateral ischemic stroke, and death.Results.-Stroke occurred in 12 of 39 patients with stage II hemodynamic failure and in 3 of 42 patients without (P = .005);stroke was ipsilateral in 11 of 39 patients with stage II hemodynamic failure and in 2 of 42 patients without (P = .004).Six deaths occurred in each group (P = .94).The age-adjusted relative risk conferred by stage II hemodynamic failure was 6.0 (95% confidence interval [CI], 1.7-21.6)for all stroke and 7.3 (95% CI, 1.6-33.4)for ipsilateral stroke.Conclusions.-StageII hemodynamic failure defines a subgroup of patients with symptomatic carotid occlusion who are at high risk for subsequent stroke when treated medically.A randomized trial evaluating surgical revascularization in this high-risk subgroup is warranted.
Dose-dependency of theophylline clearance and protein binding.
Authors: J A Fleetham, C E Bird, K Nakatsu, R D Wigle, P W Munt
Journal: Thorax (1981)

Dose-dependency in theophylline pharmacokinetics and protein binding characteristics was examined in 10 healthy male volunteers. Theophylline disposition was determined after an intravenous infusion of both 1 mg/kg and 6 mg/kg aminophylline in a randomised crossover study. There was considerable intrasubject variability in theophylline clearance but no significant dose-dependency. Theophylline protein binding was assessed by equilibrium dialysis at varying theophylline concentrations. The percentage of free non-protein bound theophylline was significantly increased at high theophylline concentrations. This increase in free theophylline would lead to a non-linear increase in the risk of toxicity with increasing drug concentration.