tbuckley/cabot-search huggingface dataset:
Aldosterone, Through Novel Signaling Proteins, Is a Fundamental Molecular Bridge Between the Genetic Defect and the Cardiac Phenotype of Hypertrophic Cardiomyopathy
Authors: Natalia Tsybouleva, Lianfeng Zhang, Suetnee Chen, Rajnikant Patel, Silvia Lutucuta, Shintaro Nemoto, Gilberto DeFreitas, Mark Entman, Blase A. Carabello, Robert Roberts, A.J. Marian
Journal: Circulation (2004)

Background— Human hypertrophic cardiomyopathy (HCM), the most common cause of sudden cardiac death in the young, is characterized by cardiac hypertrophy, myocyte disarray, and interstitial fibrosis. The genetic basis of HCM is largely known; however, the molecular mediators of cardiac phenotypes are unknown. Methods and Results— We show myocardial aldosterone and aldosterone synthase mRNA levels were elevated by 4- to 6-fold in humans with HCM, whereas cAMP levels were normal. Aldosterone provoked expression of hypertrophic markers ( NPPA , NPPB , and ACTA1 ) in rat cardiac myocytes by phosphorylation of protein kinase D (PKD) and expression of collagens ( COL1A1 , COL1A2 , and COL3A1 ) and transforming growth factor-β1 in rat cardiac fibroblasts by upregulation of phosphoinositide 3-kinase (PI3K)-p100δ. Inhibition of PKD and PI3K-p110δ abrogated the hypertrophic and profibrotic effects, respectively, as did the mineralocorticoid receptor (MR) antagonist spironolactone. Spironolactone reversed interstitial fibrosis, attenuated myocyte disarray by 50%, and improved diastolic function in the cardiac troponin T (cTnT)-Q92 transgenic mouse model of human HCM. Myocyte disarray was associated with increased levels of phosphorylated β-catenin (serine 38) and reduced β-catenin–N-cadherin complexing in the heart of cTnT-Q92 mice. Concordantly, distribution of N-cadherin, predominantly localized to cell membrane in normal myocardium, was diffuse in disarrayed myocardium. Spironolactone restored β-catenin–N-cadherin complexing and cellular distribution of N-cadherin and reduced myocyte disarray in 2 independent randomized studies. Conclusions— The results implicate aldosterone as a major link between sarcomeric mutations and cardiac phenotype in HCM and, if confirmed in additional models, signal the need for clinical studies to determine the potential beneficial effects of MR blockade in human HCM.
Predominant fusion of bone marrow-derived cardiomyocytes
Authors: J ANDRADE, J LAM, M ZAMORA, C HUANG, D FRANCO, N SEVILLA, P GRUBER, J LU, P RUIZLOZANO
Journal: Cardiovascular Research (2005)

Objectives: Here we address the capacity of bone marrow-derived cells (BMDCs) to trans-differentiate into mature myocytes under the physiological stimulus of exercise training.
Reduction in Fine Particulate Air Pollution and Mortality
Authors: Francine Laden, Joel Schwartz, Frank E. Speizer, Douglas W. Dockery
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

A large body of epidemiologic literature has found an association of increased fine particulate air pollution (PM2.5) with acute and chronic mortality. The effect of improvements in particle exposure is less clear.Earlier analysis of the Harvard Six Cities adult cohort study showed an association between long-term ambient PM2.5 and mortality between enrollment in the mid-1970s and follow-up until 1990. We extended mortality follow-up for 8 yr in a period of reduced air pollution concentrations.Annual city-specific PM2.5 concentrations were measured between 1979 and 1988, and estimated for later years from publicly available data. Exposure was defined as (1) city-specific mean PM2.5 during the two follow-up periods, (2) mean PM2.5 in the first period and change between these periods, (3) overall mean PM2.5 across the entire follow-up, and (4) year-specific mean PM2.5. Mortality rate ratios were estimated with Cox proportional hazards regression controlling for individual risk factors.We found an increase in overall mortality associated with each 10 microg/m3 increase in PM2.5 modeled either as the overall mean (rate ratio [RR], 1.16; 95% confidence interval [CI], 1.07-1.26) or as exposure in the year of death (RR, 1.14; 95% CI, 1.06-1.22). PM2.5 exposure was associated with lung cancer (RR, 1.27; 95% CI, 0.96-1.69) and cardiovascular deaths (RR, 1.28; 95% CI, 1.13-1.44). Improved overall mortality was associated with decreased mean PM2.5 (10 microg/m3) between periods (RR, 0.73; 95% CI, 0.57-0.95).Total, cardiovascular, and lung cancer mortality were each positively associated with ambient PM2.5 concentrations. Reduced PM2.5 concentrations were associated with reduced mortality risk.
Liver failure in children with hepatitis A
Authors: D Debray
Journal: Hepatology (1997)

There have been very few reports dealing with liver failure related to hepatitis A in children. Moreover, the criteria usually used for selecting patients with fulminant hepatitis A for liver transplantation have not been evaluated in children. Therefore, the current study was conducted retrospectively in a single French urban pediatric liver transplantation center to serve as a reminder of the potential severity of hepatitis A in children and to identify predictors of outcome. Children were selected by chart review using a data base system and were grouped according to outcome for analyses purposes. Over a 15-year period, 24 children with hepatitis A showed evidence of liver failure, including 6 children who did not develop hepatic encephalopathy, 7 children in whom encephalopathy occurred but resolved spontaneously, and 11 children in whom death or liver transplantation was the outcome. The mean age at onset was 6.5 years. Those with the most rapid onset of liver failure from onset of jaundice had the best chance of recovery without developing encephalopathy. Otherwise, no predictive factors of outcome were found at onset of liver failure. Among the 18 children who developed encephalopathy, the best early prognostic indicator of a poor outcome irrespective of the grade of encephalopathy, appeared to be a prothrombin time level below 21% of normal combined with a serum bilirubin level above 400 micromol/L. Therefore, these two prognostic indicators may be helpful in deciding liver transplantation in children with hepatitis A-induced fulminant liver failure.
Inhibition of the PI3K Pathway: Hope We Can Believe in?
Authors: Michiel S. van der Heijden, René Bernards
Journal: Clinical Cancer Research (2010)

The phosphoinositide 3-kinase (PI3K) pathway is one of the most commonly activated pathways in human cancer and has roles in cell proliferation, apoptosis, protein synthesis, and metabolism. The PI3K pathway can be activated by amplification or activating mutation of upstream receptor tyrosine kinases, and by mutations or deletions downstream in the pathway. Trastuzumab, a monoclonal antibody targeting the human epidermal growth factor receptor 2 (HER2), has been one of the most successful and most widely used targeted therapies. However, many HER2-positive cancers are not sensitive to HER2-based therapies or become resistant during treatment; downstream activation of the pathway is one of the causes of resistance. Because of the common activation of the PI3K pathway in cancer, compounds targeting proteins downstream in the pathway have been developed in recent years. The mammalian target of rapamycin (mTOR) inhibitors everolimus and temsirolimus have been shown to be beneficial in certain cancer types; many other inhibitors of the PI3K pathway are in various stages of clinical development. Ongoing research should clarify which molecular cancer subtypes are most susceptible to specific compounds and explore combinatorial approaches, ultimately leading to individualized patient treatment.
Plasma α-Tocopherol and Coronary Endothelium-Dependent Vasodilator Function
Authors: Scott Kinlay, James C. Fang, Hiroyuki Hikita, Ivan Ho, Danielle M. Delagrange, Balz Frei, Jung H. Suh, Marie Gerhard, Mark A. Creager, Andrew P. Selwyn, Peter Ganz
Journal: Circulation (1999)

Background —In the presence of atherosclerosis, the coronary endothelial vasomotor response to acetylcholine is frequently abnormal but is variable between patients. We tested the hypothesis that the plasma concentration of α-tocopherol is associated with the preservation of nitric oxide–mediated endothelium-dependent vasomotion. Methods and Results —We studied 15 men and 6 women (mean age 61±10 years) at coronary angiography who were not taking vitamin supplements. Coronary endothelium-dependent and -independent vasomotion was assessed by intracoronary infusions of acetylcholine and nitroglycerin. The vasomotor responses were compared with the plasma concentration of α-tocopherol and the plasma α-tocopherol concentration relative to total lipid (total cholesterol plus triglycerides). The mean plasma α-tocopherol was 25.6±6.1 μmol/L, total cholesterol 193±27 mg/dL, triglycerides 115±66 mg/dL, and α-tocopherol to total lipid 4.2±0.9 μmol · L −1 · (mmol/L) −1 . The mean vasomotor response to acetylcholine was −1% (range −33% to 28%) and to nitroglycerin 22% (range 0% to 54%). Plasma α-tocopherol was significantly correlated with the acetylcholine response ( r =0.49, P &lt;0.05) but not the nitroglycerin response ( r =0.13, P &gt;0.05). The acetylcholine response remained significant after adjustment for other potential sources of oxidant stress (total cholesterol, diabetes mellitus, smoking, angina class) ( P &lt;0.01). The relative concentration of α-tocopherol to total lipid was not related to endothelial function ( r =0.24, P =0.3, n=20). Conclusions —α-Tocopherol may preserve endothelial vasomotor function in patients with coronary atherosclerosis. This effect may be related primarily to the action of α-tocopherol in the vascular wall. Further studies that assess the impact of α-tocopherol supplementation as therapy of endothelial dysfunction are justified.
Forfar &amp; Arneil's Textbook of Pediatrics: 6th edition
Authors: Timothy Lachlan Chambers
Journal: Journal of the Royal Society of Medicine (2004)

Take, for example, single umbilical artery. A distinguished retired paediatrician telephoned me, concerned about his grandfetus which had been found through antenatal scanning to be one umbilical artery short. I scrutinized the index of the new Forfar & Arneil (FA try artery— no. Try the index of the current Nelson Textbook (same publishing stable, cheaper, American)—yes, on p. 528, a concise informative paragraph. Try Google—nearly 1300 citations, reproducible instantly on my printer and no heavy book to balance on the knees. The moral? The talents of editors and contributors might be put to better use in more contemporary information transfer. In F&A the shape of things to come is indicated by a disc behind the front cover.

So how is it for me? I have used the new FA this wayward index again) of coeliac disease; and cow's milk intolerance and constipation may be linked in the absence of atopy. Enuresis is discussed more informatively under nephrology than under psychiatry, from which it should have been blue pencilled. My main beef, however, is with this book's two-dimensional context of child life and health—a weakness common to most textbooks. The three principal elements to clinical paediatric practice are diagnosis, treatment and population medicine, all within a whole child/family framework. Though management of defined conditions and the public health of paediatrics are dealt with soundly, the real challenge to the personal physician is unravelling the cause of symptoms and relieving those which defy diagnostic classification, including the whole fascinating (and evidence-limited) spectrum of functional illness, and those which do not remit when the disease thought to cause them is treated 'successfully'. The excellent short chapter on pain management makes a good start in this respect: now for breathlessness, dizziness—and fatigue.

I thank the families of McIntosh, Helms and Smyth for loaning them to this project and salute them on the result. The style and content are even and they have largely succeeded in avoiding overlap. Do not baulk at its cost: at just over £1 per contributor you are getting a bargain (and a largely British one, despite the American spelling). This 6th edition was born (4.5 kg) just 5 years after the 5th, and the life expectancy of its knowledge base may prove even shorter. In what form the 7th will be presented I leave you, dear reader, to guess.
Recent advances: Radiotherapy
Authors: R P Symonds
Journal: BMJ (2001)

Radiotherapy is the art of using ionising radiation to destroy malignant tumours while minimising damage to normal tissue. This treatment can be highly effective. For instance, for early cancer of the larynx the cure rate is over 90%,1 and palliative radiotherapy can reduce or eliminate pain from bone metastases in 80% of patients.2 Although higher doses of radiation can produce better tumour control, the dosage that can be given is limited by the possibility of normal tissue damage. Ulceration, fistulas, severe fibrosis, and strictures may develop months or years after treatment, severely affecting the quality of life. The recent advances described in this paper focus on new techniques that produce the maximum ratio between tumour destruction and normal tissue damage and the increasing participation of patients in treatment planning.3
Nomenclature of non-neoplastic vulval conditions
Authors: C. M. RIDLEY
Journal: British Journal of Dermatology (1986)

Journal Article Nomenclature of non‐neoplastic vulval conditions Get access C. M. RIDLEY C. M. RIDLEY Whittington Hospital, London N19 5NF, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 115, Issue 6, 1 December 1986, Pages 647–648, https://doi.org/10.1111/j.1365-2133.1986.tb06643.x Published: 01 December 1986
Isolated primary oesophageal involvement by lymphoma: a rare cause of dysphagia: two case histories and a review of other published data.
Authors: B G Taal, P Van Heerde, R Somers
Journal: Gut (1993)

Primary oesophageal involvement by lymphoma in two patients, one with Hodgkin's disease and one with non-Hodgkin's lymphoma is reported. In both, there were no manifestations of the disease outside the oesophagus, which is exceptionally rare. In the patient with non-Hodgkin's lymphoma, the oesophageal tumour was the first manifestation of lymphoma. Shortly after admission he developed a tracheo-oesophageal fistula from which he died before treatment could be started. In the patient with Hodgkin's disease, isolated oesophageal lymphoma was the first relapse after a 13 year interval free of disease. As he had previously received mediastinal irradiation he was treated with combination chemotherapy that resulted in long term survival (> five years). Several other long term survivors have been described but only after radiotherapy or surgery. These findings suggest that systemic chemotherapy may be equally successful in treating isolated primary oesophageal lymphoma, thus offering an alternative for those patients in whom local treatment is contraindicated.
HDL-C and HDL-C/ApoA-I Predict Long-Term Progression of Glycemia in Established Type 2 Diabetes
Authors: Boris Waldman, Alicia J. Jenkins, Timothy M.E. Davis, Marja-Riitta Taskinen, Russell Scott, Rachel L. O’Connell, Val J. Gebski, Martin K.C. Ng, Anthony C. Keech
Journal: Diabetes Care (2014)

Low HDL cholesterol (HDL-C) and small HDL particle size may directly promote hyperglycemia. We evaluated associations of HDL-C, apolipoprotein A-I (apoA-I), and HDL-C/apoA-I with insulin secretion, insulin resistance, HbA1c, and long-term glycemic deterioration, reflected by initiation of pharmacologic glucose control.The 5-year Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study followed 9,795 type 2 diabetic subjects. We calculated baseline associations of fasting HDL-C, apoA-I, and HDL-C/apoA-I with HbA1c and, in those not taking exogenous insulin (n = 8,271), with estimated β-cell function (homeostasis model assessment of β-cell function [HOMA-B]) and insulin resistance (HOMA-IR). Among the 2,608 subjects prescribed lifestyle only, Cox proportional hazards analysis evaluated associations of HDL-C, apoA-I, and HDL-C/apoA-I with subsequent initiation of oral hypoglycemic agents (OHAs) or insulin.Adjusted for age and sex, baseline HDL-C, apoA-I, and HDL-C/apoA-I were inversely associated with HOMA-IR (r = -0.233, -0.134, and -0.230; all P < 0.001; n = 8,271) but not related to HbA1c (all P > 0.05; n = 9,795). ApoA-I was also inversely associated with HOMA-B (r = -0.063; P = 0.002; n = 8,271) adjusted for age, sex, and HOMA-IR. Prospectively, lower baseline HDL-C and HDL-C/apoA-I levels predicted greater uptake (per 1-SD lower: hazard ratio [HR] 1.13 [CI 1.07-1.19], P < 0.001; and HR 1.16 [CI 1.10-1.23], P < 0.001, respectively) and earlier uptake (median 12.9 and 24.0 months, respectively, for quartile 1 vs. quartile 4; both P < 0.01) of OHAs and insulin, with no difference in HbA1c thresholds for initiation (P = 0.87 and P = 0.81). Controlling for HOMA-IR and triglycerides lessened both associations, but HDL-C/apoA-I remained significant.HDL-C, apoA-I, and HDL-C/apoA-I were associated with concurrent insulin resistance but not HbA1c. However, lower HDL-C and HDL-C/apoA-I predicted greater and earlier need for pharmacologic glucose control.
The Reliability and Specificity of c-kit for the Diagnosis of Acute Myeloid Leukemias and Undifferentiated Leukemias
Authors: M.C. Bene, M. Bernier, R.O. Casasnovas, G. Castoldi, W. Knapp, F. Lanza, W.D. Ludwig, E. Matutes, A. Orfao, C. Sperling, M.B. van't Veer
Journal: Blood (1998)
Short term effect of feedback on fitness and health measurements on self reported appraisal of the stage of change
Authors: K I Proper, A J van der Beek, V H Hildebrandt, J W R Twisk, W van Mechelen
Journal: British Journal of Sports Medicine (2003)

Background: An individual’s current status of physical activity and nutrition and readiness to change can be determined using PACE assessment forms. Practitioners have suggested that feedback on the fitness and health components can produce a change in a subject’s awareness of their behaviour and thereby lead to a beneficial change in stage of behaviour change. Objective: To evaluate the short term effect of personalised feedback on fitness and health status on self reported appraisal of the stage of change. Methods: A total of 299 civil servants were randomised to an intervention or a reference group. After having been tested for fitness and health, the intervention group received immediate feedback on their test results, whereas the reference group did not. PACE assessment forms were completed twice: before testing and after testing (reference group), or after testing and feedback (intervention group). The time interval between was one hour. The influence of feedback was determined using a x 2 test and analysis of variance. Results: On the basis of the x 2 test, no significant effect of feedback was found on the stage of change of physical activity, nor on the stage of change with regard to nutrition. Analysis of variance results showed no significant effect on the raw PACE score as to physical activity, intake of fruit and vegetables and dietary fat. However, a significant effect was observed on the PACE score of “calorie intake and weight management”. Subjects in the intervention group significantly more often regressed on their PACE score on this topic than the reference subjects. Conclusions: Feedback at baseline on measurements of an intervention study can influence PACE scores and can be considered as a small but relevant start of the intervention itself.
Biphasic Action of Acetylcholine on Ventricular Myocardium
Authors: MILTON HOLLENBERG, SERGE CARRIERE, A. CLIFFORD BARGER
Journal: Circulation Research (1965)

Intracoronary infusions of acetylcholine have demonstrated two actions of this neurohumoral agent on ventricular myocardium: 1) an antagonism to the more forceful contractions evoked by adrenergic stimuli (sympathomimetic drugs or stellate stimulation), and 2) a sympathomimetic or positive inotropic effect (? release of a positive inotropic substance from the myocardium). The increased contractility ("rebound") was observed only after the infusion of acetylcholine was stopped; in the presence of physostigmine the "rebound" was absent. Atropine blocked both the cardio-inhibitory and cardio-excitatory actions of acetylcholine. Failure of hexamethonium and bretylium to block the "rebound" suggests that acetylcholine acts at a peripheral site. The possible catecholamine nature of the agent could not be established by direct analysis of coronary venous blood, by the use of an adrenergic beta receptor blocking agent or by pretreatment of the animals with reserpine; neither drug blocked the "rebound."
Paris‐Trousseau syndrome platelets in a child with Jacobsen's syndrome
Authors: L. Krishnamurti, J.P. Neglia, R. Nagarajan, S.A. Berry, J. Lohr, B. Hirsch, J.G. White
Journal: American Journal of Hematology (2001)

Abstract The thrombocytopenia in an infant with clinical features of Jacobsen's syndrome characterized by multiple congenital anomalies, cardiac defects, psychomotor retardation, and deletion of chromosome 11 at 11q23.3 has been evaluated. Study of his platelets in the electron microscope revealed giant alpha granules in his cells identical in appearance to those reported in the family with Paris‐Trousseau syndrome. As a result, the Paris‐Trousseau syndrome appears to be a variant of the Jacobsen syndrome, and the thrombocytopenia observed in all cases of chromosome 11q23.3 deletion due to dysmegakaryopoieses. Giant alpha granules are frequently observed in normal platelets during long‐term storage and may form in Jacobsen and Paris‐Trousseau platelets during prolonged residence in the bone marrow. Am. J. Hematol. 66:295–299, 2001. © 2001 Wiley‐Liss, Inc.
Sensory Neuron Fates Are Distinguished by a Transcriptional Switch that Regulates Dendrite Branch Stabilization
Authors: Cody J. Smith, Timothy O’Brien, Marios Chatzigeorgiou, W. Clay Spencer, Elana Feingold-Link, Steven J. Husson, Sayaka Hori, Shohei Mitani, Alexander Gottschalk, William R. Schafer, David M. Miller
Journal: Neuron (2013)
Defect of regulatory T cells in patients with Omenn syndrome
Authors: Barbara Cassani, Pietro Luigi Poliani, Daniele Moratto, Cristina Sobacchi, Veronica Marrella, Laura Imperatori, Donatella Vairo, Alessandro Plebani, Silvia Giliani, Paolo Vezzoni, Fabio Facchetti, Fulvio Porta, Luigi D. Notarangelo, Anna Villa, Raffaele Badolato
Journal: Journal of Allergy and Clinical Immunology (2010)