tbuckley/cabot-search huggingface dataset:
Abstract 17399: Nuclear Plakoglobin Mediates Differentiation of Cardiac Progenitor Cells to Adipocytes in Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Raffaella Lombardi, Maria de Graca Cabreira, James T Willerson, Ali J Marian
Journal: Circulation (2011)

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an enigmatic disease characterized by fibro-fatty infiltration of the myocardium, particularly in the right ventricle. Molecular basis of adipocytic replacement of cardiac myocyte is not fully known. We have implicated suppression of the canonical Wnt signaling in the second heart field cardiac progenitors by nuclear plakoglobin (PG), a desmosome protein, in the pathogenesis of ARVC. However, the direct role of PG in a phenotypic switch from myogenesis to adipogenesis remains unestablished. To delineate the direct role of PG in adipogenesis in ARVC, we over-expressed and deleted PG in cardiac myocyte lineage in vivo. We also expressed a truncated PG, known to cause ARVC in humans, in the heart, as a control. Over-expression of wild type (WT) and mutant PG led to their nuclear localization. The WT but not the mutant PG also incorporated into desmosomes. The mutant PG exhibited reduced binding affinity to other desmosome proteins and predominantly was localized to cytosol and nucleus but not the membrane. Over-expression of WT and mutant PG led to excess adipocytes in the heart, cardiac dysfunction and premature death. FACS sorted c-Kit+/Sca1+ cells isolated from the hearts of transgenic PG mice showed increased adipogenesis and mRNA levels of adipogenic markers KLF15, BMP-7, IGFBP-5 and Wnt5B but decreased level of CTGF, an inhibitor of adipogenesis. Treatment with BIO, a known activator of the canonical Wnt signaling, reversed enhanced adipogenesis, in a dose-dependent manner. In contrast to the over-expressors, c-Kit+/Lin-/Flk- cells isolated from 12-day PG-null embryos showed suppressed adipogenesis and increased levels of canonical Wnt signaling markers, leading to embryonic lethality. These findings establish the direct role of nuclear PG in mediating transdifferentiation of cardiac progenitors cells to adipocytes in ARVC, a phenotypic switch that is induced by suppression of the canonical Wnt signaling and rescued upon activation of the canonical Wnt signaling.
Predictors of Ineffective Cough during a Chest Infection in Patients with Stable Amyotrophic Lateral Sclerosis
Authors: Jesús Sancho, Emilio Servera, Juan Díaz, Julio Marín
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

In patients with neuromuscular diseases, a chest infection is associated with a reduction in respiratory muscle function that may result in decreased cough effectiveness.To determine if a clinical or functional parameter in patients with amyotrophic lateral sclerosis (ALS) in a stable condition could predict spontaneous cough ineffectiveness during a respiratory tract infection.Forty consecutive patients with ALS referred to our Respiratory Care Unit were studied during a one-year follow-up.FEV(1), FVC, FEV(1)/FVC, peak cough flow (PCF), peak velocity time (PVT), maximum inspiratory and expiratory pressures, and bulbar dysfunction evaluation using the Norris scale bulbar subscore (NBS). A total of 26 patients (65%) had spontaneous cough ineffectiveness during a respiratory tract infection. The best variables to predict nonassisted cough during a respiratory tract infection were NBS (p < 0.01) with a cutoff point of 29 (sensitivity, 0.89; specificity, 0.90; positive predicted value, 0.88; negative predictive value, 0.87), PCF (p < 0.001) with a cutoff point of 4.25 L/s (sensitivity, 0.74; specificity, 0.85; positive predictive value, 0.71; negative predictive value, 0.85), and PCF/PVT (p < 0.001) with a cutoff point of 28.88 L/s(2) (sensitivity, 0.77; specificity, 0.96; positive predictive value, 0.91; negative predictive value, 0.89).In patients with stable ALS, bulbar dysfunction (NBS < 29), PCF (< 4.25 L/s), and PCF/PVT (< 28.88 L/s(2)) could predict the risk of ineffective spontaneous cough during a respiratory tract infection.
A randomized, investigator-blinded, controlled pilot study to evaluate the safety and efficacy of a poly-N-acetyl glucosamine–derived membrane material in patients with venous leg ulcers
Authors: Teresa J. Kelechi, Martina Mueller, Cheryl S. Hankin, Amy Bronstone, John Samies, Phyllis A. Bonham
Journal: Journal of the American Academy of Dermatology (2011)
Metabolism of Vitamin D3-3H in Human Subjects: Distribution in Blood, Bile, Feces, and Urine*
Authors: Louis V. Avioli, Sook Won Lee, Joseph E. McDonald, Judith Lund, Hector F. DeLuca
Journal: Journal of Clinical Investigation (1967)

Vitamin D(3)-(3)H has been administered intravenously to seven normal subjects, three patients with biliary fistulas, and four patients with cirrhosis. Plasma D(3)-(3)H half-times normally ranged from 20 to 30 hours. in vivo evidence that a metabolic transformation of vitamin D occurs was obtained, and a polar biologically active vitamin D metabolite was isolated from plasma. Urinary radioactivity averaged 2.4% of the administered dose for the 48-hour period after infusion, and all the excreted radioactivity represented chemically altered metabolites of vitamin D. The metabolites in urine were mainly water-soluble, with 26% in conjugated form. From 3 to 6% of the injected radioactivity was excreted in the bile of subjects with T-tube drainage and 5% in the feces of patients having no T-tube. The pattern of fecal and biliary radioactivity suggested that the passage of vitamin D and its metabolites from bile into the intestine represents an essential stage for the fecal excretion of vitamin D metabolites in man. Abnormally slow plasma disappearance of vitamin D(3)-(3)H in patients with cirrhosis was associated with a significant decrease in the quantity and rate of glucuronide metabolite excretion in the urine.
Enhancing Mitochondrial Ca <sup>2+</sup> Uptake in Myocytes From Failing Hearts Restores Energy Supply and Demand Matching
Authors: Ting Liu, Brian O'Rourke
Journal: Circulation Research (2008)

Mitochondrial ATP production is continually adjusted to energy demand through coordinated increases in oxidative phosphorylation and NADH production mediated by mitochondrial Ca 2+ ([Ca 2+ ] m ). Elevated cytosolic Na + impairs [Ca 2+ ] m accumulation during rapid pacing of myocytes, resulting in a decrease in NADH/NAD + redox potential. Here, we determined 1) if accentuating [Ca 2+ ] m accumulation prevents the impaired NADH response at high [Na + ] i ; 2) if [Ca 2+ ] m handling and NADH/NAD + balance during stimulation is impaired with heart failure (induced by aortic constriction); and 3) if inhibiting [Ca 2+ ] m efflux improves NADH/NAD + balance in heart failure. [Ca 2+ ] m and NADH were recorded in cells at rest and during voltage clamp stimulation (4Hz) with either 5 or 15 mmol/L [Na + ] i . Fast [Ca 2+ ] m transients and a rise in diastolic [Ca 2+ ] m were observed during electric stimulation. [Ca 2+ ] m accumulation was [Na + ] i -dependent; less [Ca 2+ ] m accumulated in cells with 15 Na + versus 5 mmol/L Na + and NADH oxidation was evident at 15 mmol/L Na + , but not at 5 mmol/L Na + . Treatment with either the mitochondrial Na + /Ca 2+ exchange inhibitor CGP-37157 (1 μmol/L) or raising cytosolic P i (2 mmol/L) enhanced [Ca 2+ ] m accumulation and prevented the NADH oxidation at 15 mmol/L [Na + ] i . In heart failure myocytes, resting [Na + ] i increased from 5.2±1.4 to 16.8±3.1mmol/L and net NADH oxidation was observed during pacing, whereas NADH was well matched in controls. Treatment with CGP-37157 or lowering [Na + ] i prevented the impaired NADH response in heart failure. We conclude that high [Na + ] i (at levels observed in heart failure) has detrimental effects on mitochondrial bioenergetics, and this impairment can be prevented by inhibiting the mitochondrial Na + /Ca 2+ exchanger.
Longitudinal Psychiatric Symptoms in Prodromal Huntington’s Disease: A Decade of Data
Authors: Eric A. Epping, Ji-In Kim, David Craufurd, Thomas M. Brashers-Krug, Karen E. Anderson, Elizabeth McCusker, Jolene Luther, Jeffrey D. Long, Jane S. Paulsen
Journal: American Journal of Psychiatry (2015)

Psychiatric symptoms are a significant aspect of Huntington's disease, an inherited neurodegenerative illness. The presentation of these symptoms is highly variable, and their course does not fully correlate with motor or cognitive disease progression. The authors sought to better understand the development and longitudinal course of psychiatric manifestations in individuals who carry the Huntington's disease mutation, starting from the prodromal period prior to motor diagnosis.Longitudinal measures for up to 10 years of psychiatric symptoms from the Symptom Checklist-90-Revised were obtained from 1,305 participants (1,007 carrying the Huntington's disease mutation and 298 without [classified as controls]) and 1,235 companions enrolled in the Neurobiological Predictors of Huntington's Disease (PREDICT-HD) study. Participants with the mutation were stratified into three groups according to probability of motor diagnosis within 5 years. Using linear mixed-effects regression models, differences in psychiatric symptoms at baseline and over time between the mutation-positive groups and the controls were compared, as well as between ratings by mutation-positive participants and their companions.Nineteen of 24 psychiatric measures (12 participant ratings and 12 companion ratings) were significantly higher at baseline and showed significant increases longitudinally in the individuals with the Huntington's disease mutation compared with controls. The differences were greatest in comparisons of symptom reports from companions compared with self-reports, especially in participants who were closest to motor diagnosis.The results indicate that psychiatric manifestations develop more often than previously thought in the Huntington's disease prodrome. Symptoms also increase with progression of disease severity. Greater symptom ratings by companions than by mutation-positive participants suggest decreasing awareness in those affected.
Bronchoalveolar lavage findings in patients with chronic nonproductive cough
Authors: LP McGarvey, P Forsythe, LG Heaney, J MacMahon, M Ennis
Journal: European Respiratory Journal (1999)

Mast cells and eosinophils may play a role in the pathophysiology of chronic cough in nonasthmatics. It is unknown, however, whether degranulation of these cells occurs in the airways of such patients. Thirty-five nonsmoking patients referred with a chronic nonproductive cough (mean cough duration 76.2 months) were evaluated using a comprehensive diagnostic protocol. Bronchoalveolar lavage (BAL) cell differentials and BAL histamine, tryptase and eosinophilic cationic protein (ECP) concentrations were determined. Ten nonsmoking healthy volunteers served as controls. Diagnostic subgroups were identified: eight postnasal drip syndrome (PNDS), seven cough variant asthma (CVA), seven gastro-esophageal reflux (GOR), seven dual aetiology and six idiopathic. Nonasthmatic coughers (NAC) were characterized as those patients without bronchial hyperresponsiveness on histamine challenge and whose cough had either responded to therapy for PNDS or GOR or failed to improve with antiasthma therapy. There was a significant increase in both eosinophil and mast cell numbers (p<0.05) and in histamine levels (p = 0.027) when NAC patients were compared with controls. Tryptase and ECP levels were elevated in 7 of 23 and 6 of 23 NAC patients, respectively. In conclusion, airway inflammatory cell numbers are not only increased but also activated, suggesting an important role for airways inflammation in the pathophysiology of chronic nonproductive cough.
Treatment of refractory thrombocytopenic purpura with cyclophosphamide
Authors: Michael Verlin, Russell K. Laros, John A. Penner
Journal: American Journal of Hematology (1976)

Cyclophosphamide, an immunosuppressive agent, was administered as an additional mode of therapy to 30 patients with idiopathic thrombocytopenic purpura (ITP) refractory to conventional management. Of 22 previously tested by splenectomy an excellent response was achieved in 12, who remained in complete hematologic remission for 14-96 months after therapy was discontinued; a fair response in 3, with definite increase in platelets, but not to normal levels; and a poor response in 7 who failed to improve. Of 8 nonsplenectomized patients who failed to respond to steroids or maintain a response after steroids were discontinued, 4 were considered excellent, 1 required continued therapy to remain in remission (good response), 2 were fair, and 1 was poor. Remission was observed in 2-10 weeks in both groups and appeared to be related to duration of disease; presence of disease for less than 1 year was associated with a much better response to treatment (11 of 15) when compared with disorders lasting over 2 years (6 of 15). Cyclophosphamide therapy offers additional means of treating patients with ITP who fail to respond to conventional therapy and may serve as an alternative to splenectomy when surgery is contraindicated.
Exacerbation of heart failure in adiponectin-deficient mice due to impaired regulation of AMPK and glucose metabolism
Authors: Y LIAO, S TAKASHIMA, N MAEDA, N OUCHI, K KOMAMURA, I SHIMOMURA, M HORI, Y MATSUZAWA, T FUNAHASHI, M KITAKAZE
Journal: Cardiovascular Research (2005)

Objective: Insulin resistance (IR) was reported to be associated with chronic heart failure (CHF). Adiponectin, an insulin-sensitizing hormone with anti-inflammatory activity, improves energy metabolism via AMP-activated protein kinase (AMPK). AMPK deficiency is associated with depressed cardiac function under stress conditions. However, it is not clear whether adiponectin plays an important role in CHF. We hypothesize that deficiency of adiponectin might result in deterioration of heart failure.
591 BACTERIAL DNA MEASUREMENTS IN PATIENTS WITH CIRRHOSIS UNDERGOING TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNT (TIPS) INSERTION
Authors: C. Mortensen, S. Karlsen, H. Gronbak, D.T. Nielsen, S. Frevert, O. Clemmesen, S. Moller, J.S. Jensen, F. Bendtsen
Journal: Journal of Hepatology (2013)
Phenethyl Isothiocyanate Inhibits Angiogenesis <i>In vitro</i> and <i>Ex vivo</i>
Authors: Dong Xiao, Shivendra V. Singh
Journal: Cancer Research (2007)

Abstract Previous studies, including those from our laboratory, have revealed that phenethyl isothiocyanate (PEITC), a constituent of many edible cruciferous vegetables, not only affords significant protection against chemically induced cancer in animal models but also inhibits growth of cancer cells in culture and in vivo by causing cell cycle arrest and apoptosis induction. We now report a novel response to PEITC involving inhibition of angiogenesis in vitro and ex vivo at pharmacologically achievable concentrations. The PEITC treatment caused a decrease in survival of human umbilical vein endothelial cells (HUVEC) in a concentration- and time-dependent manner. The capillary-like tube structure formation (in vitro neovascularization) and migration (invasion potential) by HUVEC was also inhibited significantly in the presence of PEITC at pharmacologically relevant concentrations (&amp;lt;1 μmol/L). The PEITC-mediated inhibition of angiogenic features of HUVEC in vitro was associated with suppression of vascular endothelial growth factor (VEGF) secretion, down-regulation of VEGF receptor 2 protein levels, and inactivation of prosurvival serine-threonine kinase Akt. The PEITC treatment reduced migration by PC-3 human prostate cancer cells, which correlated with inactivation of Akt and suppression of VEGF, epidermal growth factor (EGF), and granulocyte colony-stimulating factor (G-CSF) secretion. The PEITC-mediated inhibition of PC-3 cell migration was statistically significantly attenuated by ectopic expression of constitutively active Akt. Most importantly, PEITC treatment inhibited ex vivo angiogenesis as revealed by chicken egg chorioallantoic membrane assay. In conclusion, the present study suggests that inhibition of angiogenesis may be an important mechanism in cancer chemoprevention by PEITC. [Cancer Res 2007;67(5):2239–46]
CHANGES IN LABORATORY AND FIELD-BASED MEASUREMENTS IN HIGHLY TRAINED ENDURANCE RUNNERS ACROSS A TRAINING YEAR
Authors: A Galbraith, JG Hopker, L Passfield
Journal: British Journal of Sports Medicine (2013)

We examined the effects of one year9s endurance training on laboratory and field-based fitness measures in highly trained distance runners. Fourteen distance runners (mean±SD: age 28±8 y, body mass 67.0±6.3 kg, VO<sub>2max</sub> 69.8±6.3 mL.kg<sup>−1</sup>.min<sup>−1</sup>) with at least 2 years competitive experience completed 5 laboratory and 9 field tests across a 12 month period, during which time training volume and intensity were monitored. The laboratory tests measured VO<sub>2max</sub>, lactate threshold (LT) and running economy, whilst the field tests measured critical speed (CS) and the maximum distance that can be performed above CS (D'). The data were analyzed using repeated measures ANOVA, correlation coefficients and multiple regression. VO<sub>2max</sub> (L.min<sup>−1</sup>) changed during the year, being higher in October (5.0 L.min<sup>−1</sup>, <i>P</i>&lt;0.01) and January (5.0 L.min<sup>−1</sup>, <i>P</i>=0.01), than in April (4.7 L.min<sup>−1</sup>). There were no changes in the other laboratory measures during the study. Total distance covered in training changed during the year, being higher in January-February (474 km) than May-July (333 km; <i>P</i>=0.01) and July-August (339 km; <i>P</i>=0.02). Total distance covered in the training period preceding the laboratory test correlated with LT and running economy (<i>r</i>=0.55, <i>P</i>&lt;0.01; <i>r</i>=-0.33, <i>P</i>=0.01). CS changed during the year (<i>P</i>=0.02), being at its lowest in August (4.90 m.s<sup>−1</sup>) and reaching a peak in February (4.99 m.s<sup>−1</sup>). There were no differences in D' across the study (<i>P</i>=0.11). Total training distance and percentage of training time spent above threshold velocity explained 33% of the variation in CS. Increasing training distance and the percentage of training time above threshold velocity was shown to increase CS.
Rhinovirus and Respiratory Syncytial Virus in Wheezing Children Requiring Emergency Care
Authors: GARY P. RAKES, EURICO ARRUDA, JIM M. INGRAM, GATES E. HOOVER, JUAN C. ZAMBRANO, FREDERICK G. HAYDEN, THOMAS A. E. PLATTS-MILLS, PETER W. HEYMANN
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

This cross-sectional emergency department study of 70 wheezing children and 59 control subjects (2 mo to 16 yr of age) examined the prevalence of respiratory viruses and their relationship to age, atopic status, and eosinophil markers. Nasal washes were cultured for respiratory viruses, assayed for respiratory syncytial virus (RSV) antigen, and tested for coronavirus and rhinovirus RNA using reverse transcription-PCR (RT-PCR). Also evaluated were eosinophil numbers and eosinophil cationic protein (ECP) in both nasal washes and serum, along with total IgE and specific IgE antibody in serum. Respiratory viruses were detected in 82% (18 of 22) of wheezing infants younger than 2 yr of age and in 83% (40 of 48) of older wheezing children. The predominant pathogens were RSV in infants (detected in 68% of wheezing subjects) and rhinovirus in older wheezing children (71%), and both were strongly associated with wheezing (p < 0.005). RSV was largely limited to wheezing children younger than 24 mo of age, but rhinovirus was detected by RT-PCR in 41% of all infants and in 35% of nonwheezing control subjects older than 2 yr of age. After 2 yr of age the strongest odds for wheezing were observed among those who had a positive RT-PCR test for rhinovirus together with a positive serum radioallergosorbent testing (RAST), nasal eosinophilia, or elevated nasal ECP (odds ratios = 17, 21, and 25, respectively). Results from this study demonstrate that a large majority of emergent wheezing illnesses during childhood (2 to 16 yr of age) can be linked to infection with rhinovirus, and that these wheezing attacks are most likely in those who have rhinovirus together with evidence of atopy or eosinophilic airway inflammation.
Effects of Therapy on Rate of Absorption of Calcium from Gut in Disorders of Calcium Homoeostasis
Authors: J. Reeve, R. Hesp, N. Veall
Journal: BMJ (1974)

A development of the double-tracer calcium absorption test, in which a function is derived for single-passage entry rate from the gut with time, has been assessed in various disorders of calcium homoeostasis. Single tests are diagnostically useful in calcium malabsorption but because of the wide spectrum of normal values a single test can only moderately enhance the accuracy of the diagnosis of hypercalcaemic states made primarily by other methods. On the other hand serial studies in the same subject can be much more informative because the test is normally highly reproducible if conditions are unchanged. Serial studies play an important part in assessing the efficacy of established methods of treatment in disorders of calcium homoeostasis and should be particularly helpful in studying the effects of new forms of therapy on the absorption process.
Angiogenesis by Implantation of Peripheral Blood Mononuclear Cells and Platelets Into Ischemic Limbs
Authors: Osamu Iba, Hiroaki Matsubara, Yoshihisa Nozawa, Soichiro Fujiyama, Katsuya Amano, Yasukiyo Mori, Hiroyuki Kojima, Toshiji Iwasaka
Journal: Circulation (2002)

Peripheral blood mononuclear cells (PBMNCs), platelets, and polymorphonuclear leukocytes (PMNs) contain various angiogenic factors and cytokines.
HLA-DRB1 genes and patients with late onset rheumatoid arthritis
Authors: J-P Hellier, J-F Eliaou, J-P Daurès, J Sany, B Combe
Journal: Annals of the Rheumatic Diseases (2001)

To determine the influence of HLA-DRB*1 genes on susceptibility to and severity of rheumatoid arthritis (RA) in patients with late onset compared with younger onset disease.The clinical, biological, and HLA-DRB1 typing characteristics of two groups of patients were studied retrospectively. Group 1 consisted of 262 patients whose disease onset was before or at the age of 60 (young onset RA (YORA)). Group 2 included 60 patients whose illness began after the age of 60 (elderly onset RA (EORA)).The shared epitope level was similarly increased in both groups of patients compared with normal controls (195/262 (74%) in group 1 and 43/60 (72%) in group 2 v 645/1609 (40.1%) in controls). No differences were noted between the two groups of patients for each separate disease related allele. In contrast, when studying all HLA-DRB1*04 RA related alleles as a group, these alleles were underrepresented in EORA compared with YORA (22/60 (37%) v 135/262 (52%); odds ratio 2.0; 95% confidence interval 1.0 to 3.3). An inverse trend was seen for HLA-DRB1*01 alleles. There were no differences in biological characteristics or extra-articular manifestations between the patient groups. The differences noted in radiological evaluation or the number of prescribed disease modifying antirheumatic drugs seemed to be linked with differences in disease duration.HLA-DRB1 RA related alleles influence both EORA and YORA. However, HLA-DRB1*04 RA linked alleles are not as closely associated with RA in the elderly as they are in younger patients. This suggests that the importance of these genes in the susceptibility to RA may be lower in elderly patients.