tbuckley/cabot-search huggingface dataset:
The Human <i>let-7a-3</i> Locus Contains an Epigenetically Regulated MicroRNA Gene with Oncogenic Function
Authors: Bodo Brueckner, Carlo Stresemann, Ruprecht Kuner, Cora Mund, Tanja Musch, Michael Meister, Holger Sültmann, Frank Lyko
Journal: Cancer Research (2007)

Abstract MicroRNAs (miRNAs) are small noncoding RNAs that repress their target mRNAs by complementary base pairing and induction of the RNA interference pathway. It has been shown that miRNA expression can be regulated by DNA methylation and it has been suggested that altered miRNA gene methylation might contribute to human tumorigenesis. In this study, we show that the human let-7a-3 gene on chromosome 22q13.31 is associated with a CpG island. Let-7a-3 belongs to the archetypal let-7 miRNA gene family and was found to be methylated by the DNA methyltransferases DNMT1 and DNMT3B. The gene was heavily methylated in normal human tissues but hypomethylated in some lung adenocarcinomas. Let-7a-3 hypomethylation facilitated epigenetic reactivation of the gene and elevated expression of let-7a-3 in a human lung cancer cell line resulted in enhanced tumor phenotypes and oncogenic changes in transcription profiles. Our results thus identify let-7a-3 as an epigenetically regulated miRNA gene with oncogenic function and suggest that aberrant miRNA gene methylation might contribute to the human cancer epigenome. [Cancer Res 2007;67(4):1419–23]
Differences in Cardiac Hypertrophy in Exercise and in Hypoxia
Authors: EDWARD J. VAN LIERE, BARBARA BAUGH KRAMES, DAVID W. NORTHUP
Journal: Circulation Research (1965)

A group of rats, including both sexes, was exercised on an electrically-driven treadmill at the rate of one mile per hour for two hours daily to a total of 60 hours. Another group, also including both sexes, was exposed to intermittent hypoxia for eight hours daily, six days per week, for four weeks at a barometric pressure of 303 mm Hg corresponding to a simulated altitude of approximately 24,000 feet (7,315 m). All these animals showed significant hypertrophy of both ventricles. Exercise produced about the same percentage of weight increase in the right and also in the left ventricular walls. The per cent increase of the right ventricular wall relative to that of the left ventricular wall was greater after intermittent hypoxia than after exercise. The ratio of left ventricular weight/right ventricular weight was significantly less in the hypoxic group than in the exercised group. This indicates a relative right ventricular hypertrophy produced by the intermittent hypoxia. Reasons are given to indicate that the pulmonary hypertension associated with hypoxia is the cause of this right ventricular predominance.
Bosentan for sarcoidosis associated pulmonary arterial hypertension (BoSAPH) was effective in advanced parenchymal lung disease
Authors: Robert Baughman, Daniel Culver, Francis Cordova, Maria Padilla, Kevin Gibson, Elyse Lower, Peter Engel
Journal: European Respiratory Journal (2012)

Introduction : We reported significant improvement in pulmonary artery mean (PAM) and pulmonary vascular resistance (PVR) for those treated with 16 weeks (wks) of bosentan (BOS) versus no change in those treated with placebo (PLA) for sarcoidosis associated pulmonary arterial hypertension (SAPH). Purpose of the study : To determine whether patients with advanced parenchymal disease were less likely to respond to BOS. Methods : Patients with SAPH confirmed by right heart catheterization (RHC) were randomized 2:1 to receive either BOS or PLA. After 16 wks of therapy, patients underwent repeat RHC. Patients had forced vital capacity (FVC) and Scadding chest x-ray (CXR) stage. Results : Of the 25 patients treated with BOS, 2 stopped study drug before wk 8. At 16 wks, 21had repeated RHC. Patients were subgrouped into those with FVC% ≥70% predicted (FVC≥70%) or below 70% (FVC≤70%) and those with CXR stage 0-3 (CXR<4) versus stage 4 (CXR=4). The table demonstrates the changes in PAM and PVR. There was significant improvement in PAM and PVR for those with FVC<70% but was not for those with FVC≥70%. No changes were seen for the PLA group.

View this table:

PAM and PVR





Conclusion : After 16 wks of treatment, bosentan therapy was associated with a significant improvement in PAM and PVR. These changes remained significant for patients with an FVC<70% predicted. SAPH patients with advanced parenchymal lung disease may respond to vasodilatory therapy.
A traditional herbal medicine enhances bilirubin clearance by activating the nuclear receptor CAR
Authors: Wendong Huang, Jun Zhang, David D. Moore
Journal: Journal of Clinical Investigation (2004)

Yin Zhi Huang, a decoction of Yin Chin (Artemisia capillaris) and three other herbs, is widely used in Asia to prevent and treat neonatal jaundice. We recently identified the constitutive androstane receptor (CAR, NR1I3) as a key regulator of bilirubin clearance in the liver. Here we show that treatment of WT and humanized CAR transgenic mice with Yin Zhi Huang for 3 days accelerates the clearance of intravenously infused bilirubin. This effect is absent in CAR knockout animals. Expression of bilirubin glucuronyl transferase and other components of the bilirubin metabolism pathway is induced by Yin Zhi Huang treatment of WT mice or mice expressing only human CAR, but not CAR knockout animals. 6,7-Dimethylesculetin, a compound present in Yin Chin, activates CAR in primary hepatocytes from both WT and humanized CAR mice and accelerates bilirubin clearance in vivo. We conclude that CAR mediates the effects of Yin Zhi Huang on bilirubin clearance and that 6,7-dimethylesculetin is an active component of this herbal medicine. CAR is a potential target for the development of new drugs to treat neonatal, genetic, or acquired forms of jaundice.
Hyperplastic and Inflammatory Nodules in the Canine Mammary Gland&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: A. M. Cameron, L. J. Faulkin
Journal: JNCI Journal of the National Cancer Institute (1971)

Techniques developed for demonstrating hyperplastic lesions in mammary glands of rodents were applied to whole mammary glands of untreated female beagle dogs. Any unusual structural change, as compared to the normal lobularity of the mammary gland, was considered an atypical nodule. Such nodules were classified histologically as normal, inflammatory, or proliferative. Evaluation of the mammary gland of the dog by the techniques described could substantially shorten the time required and improve the accuracy of oncologicand drug evaluation studies.
Effect of exercise-induced dehydration on endurance performance: evaluating the impact of exercise protocols on outcomes using a meta-analytic procedure
Authors: Eric D B Goulet
Journal: British Journal of Sports Medicine (2012)

Objective It is purported that exercise-induced dehydration (EID), especially if ≥ 2% bodyweight, impairs endurance performance (EP). Field research shows that athletes can achieve outstanding EP while dehydrated &gt; 2% bodyweight. Using the meta-analytic procedure, this study compared the findings of laboratory-based studies that examined the impact of EID upon EP using either ecologically valid (EV) (time-trial exercise) or non-ecologically valid (NEV) (clamped-intensity exercise) exercise protocols. Methods EP outcomes were put on the same scale and represent % changes in power output between euhydrated and dehydrated exercise tests. Random-effects model meta-regressions and weighted mean effect summaries, mixed-effects model analogue to the ANOVAs and magnitude-based effect statistics were used to delineate treatment effects. Main results Fifteen research articles were included, producing 28 effect estimates, representing 122 subjects. Compared with euhydration, EID increased (0.09±2.60%, (p=0.9)) EP under time-trial exercise conditions, whereas it reduced it (1.91±1.53%, (p&lt;0.05)) with NEV exercise protocols. Only with NEV exercise protocols did EID ≥ 2% body weight impair EP (p=0.03). Conclusions Evidence indicates that (1) EID ≤ 4% bodyweight is very unlikely to impair EP under real-world exercise conditions (time-trial type exercise) and; (2) under situations of fixed-exercise intensity, which may have some relevance for military and occupational settings, EID ≥ 2% bodyweight is associated with a reduction in endurance capacity. The 2% bodyweight loss rule has been established from findings of studies using NEV exercise protocols and does not apply to out-of-doors exercise conditions. Athletes are therefore encouraged to drink according to thirst during exercise.
ABT-450/r–Ombitasvir and Dasabuvir with or without Ribavirin for HCV
Authors: Peter Ferenci, David Bernstein, Jacob Lalezari, Daniel Cohen, Yan Luo, Curtis Cooper, Edward Tam, Rui T. Marinho, Naoky Tsai, Anders Nyberg, Terry D. Box, Ziad Younes, Pedram Enayati, Sinikka Green, Yaacov Baruch, Bal Raj Bhandari, Florin Alexandru Caruntu, Thomas Sepe, Vladimir Chulanov, Ewa Janczewska, Giuliano Rizzardini, Judit Gervain, Ramon Planas, Christophe Moreno, Tarek Hassanein, Wangang Xie, Martin King, Thomas Podsadecki, K. Rajender Reddy
Journal: New England Journal of Medicine (2014)

The interferon-free regimen of ABT-450 with ritonavir (ABT-450/r), ombitasvir, and dasabuvir with or without ribavirin has shown efficacy in inducing a sustained virologic response in a phase 2 study involving patients with hepatitis C virus (HCV) genotype 1 infection. We conducted two phase 3 trials to examine the efficacy and safety of this regimen in previously untreated patients with HCV genotype 1 infection and no cirrhosis.
Progressive increase in body mass index is not associated with a progressive increase in joint space narrowing in obese women with osteoarthritis of the knee
Authors: M-P H. Le Graverand, K Brandt, S A Mazzuca, D Raunig, E Vignon
Journal: Annals of the Rheumatic Diseases (2008)

Given that obesity is a risk factor for osteoarthritis (OA) of the knee, a study was undertaken to determine whether progressively higher body mass index (BMI) among obese women is associated with progressive increases in joint space narrowing (JSN).Medial compartment JSN over 12 months in Lyon Schuss radiographs of 60 obese women (BMI 30.0-50.5 kg/m(2)) with radiographic and symptomatic OA was compared with that in 81 non-obese women (BMI <28 kg/m(2)) with normal radiographs and minimal or no symptoms of knee OA.Among the patients with OA, higher BMI tended to be associated with a higher Kellgren and Lawrence (KL) grade of OA severity. JSN in the non-obese controls was negligible, but in the 30 patients with KL grade 2 and KL grade 3 knees, mean (SD) JSN was 0.12 (0.31) mm and 0.32 (0.50) mm, respectively (p<0.005 and p<0.001). No association was seen between baseline BMI and 12-month JSN in patients with OA; indeed, the regression plot suggested a slight inverse relationship between the two.In obese patients with OA, progressively higher BMI values were not accompanied by a progressively increasing rate of JSN. Joint loading was not evaluated, but it is possible that marked obesity limited the functional capacity of some subjects with OA, protecting their knees from loading. For investigators considering eligibility criteria for a trial of a structure-modifying OA drug, these data suggest that recruitment of patients with a BMI much higher than 30 kg/m(2) will not enrich the sample of subjects who will have more rapid JSN than those with a BMI of only 30 kg/m(2).
Efficacy of rotigotine for treatment of moderate-to-severe restless legs syndrome: a randomised, double-blind, placebo-controlled trial
Authors: Claudia Trenkwalder, Heike Beneš, Werner Poewe, Wolfgang H Oertel, Diego Garcia-Borreguero, Al W de Weerd, Luigi Ferini-Strambi, Pasquale Montagna, Per Odin, Karin Stiasny-Kolster, Birgit Högl, K Ray Chaudhuri, Markku Partinen, Erwin Schollmayer, Ralf Kohnen
Journal: The Lancet Neurology (2008)
Growth hormone and the kidney
Authors: R N Fine
Journal: Journal of the American Society of Nephrology (1991)

Hypothalamic production of growth hormone releasing hormone stimulates the anterior pituitary gland to release growth hormone (GH). The clinical manifestations of GH on tissues are either direct or are mediated by insulin-like growth factors (IGF). Both the somatic effects of GH and the renal manifestations of an increase in glomerular filtration rate and renal plasma flow are mediated by IGF. The increase in glomerular filtration rate/renal plasma flow that occurs with either exogenous or endogenous GH is not apparent in patients with chronic renal failure (CRF); therefore, it is unlikely that recombinant human growth hormone (rhGH) treatment of patients with CRF will result in glomerular hyperfiltration. Longitudinal studies are required to determine if the glomerulosclerosis and renal functional impairment occurring in GH and growth hormone releasing hormone transgenic mice occurs after rhGH treatment of growth-retarded uremic rats with GH resulted in an improvement in growth velocity. This led to preliminary studies in growth-retarded children with CRF by using rhGH. The acceleration of growth velocity was dramatic despite the fact that GH levels are elevated in uremia. The elevated IGF carrier proteins in uremic children may contribute to the growth retardation. Treatment with rhGH may be efficacious by stimulating a net increase in the free (unbound) IGF levels. Hyposecretion of GH may contribute to the failure to achieve optimal growth after successful renal transplantation. Treatment with rhGH may be efficacious in improving the growth velocity of renal allograft recipients.
Diagnostic and clinical implications of the different genotypes of hepatitis C virus
Authors: Jens Bukh, Roger H. Miller
Journal: Hepatology (1994)

ABSTRACT Hepatitis C virus (HCV) samples in 155 sera, from patients with chronic non–A, non–B liver disease and blood donors, were grouped into four genotypes (I, II, III, and IV) by amplification of core–gene sequences by polymerase chain reaction with type–specific primers. HCV genotypes were compared with various HCV–associated antibodies detectable by the first–generation ELISA (ELISA–1) with C100–3 protein and a second–generation immunoblot assay with four recombinant HCV proteins. Antibodies to C100–3 protein and those to its subsequence (5-1-1) were detected in 13 (93%) and 12 (86%), respectively, of 14 sera with genotype I HCV; 56 (79%) and 58 (82%) of 71 sera with genotype II; 13 (34%) and 6 (16%) of 38 sera with genotype III; and 11 (34%) and 4 (13%) of 32 sera with genotype IV. Amino acid sequences of C100–3 of genotype I HCV are conserved by ˜90% in genotype II, but only by ˜75% in genotypes III and IV. The sensitivity of ELSA–1, therefore, would be influenced by heterogeneity in C100–3 sequences of different genotypes.
Ketosis-Prone Type 2 Diabetes Mellitus and &lt;emph type="ital"&gt;Human Herpesvirus 8&lt;/emph&gt; Infection in Sub-Saharan Africans
Authors: Eugène Sobngwi
Journal: JAMA (2008)

An atypical form of type 2 diabetes mellitus (DM-2) is revealed by ketosis (ketosis-prone type 2 diabetes mellitus), frequently occurring in individuals who are black and of African origin, and characterized by an acute onset requiring transient insulin therapy. Its sudden onset suggests precipitating factors.To investigate the putative role of human herpesvirus 8 (HHV-8) in the pathogenesis of ketosis-prone DM-2.A cross-sectional study in which antibodies were searched against latent and lytic HHV-8 antigens using immunofluorescence. The presence of HHV-8 in genomic DNA was investigated in 22 of the participants at clinical onset of diabetes. We also tested whether HHV-8 was able to infect human pancreatic beta cells in culture in vitro. The study was conducted at Saint-Louis University Hospital, Paris, France, from January 2004 to July 2005. All participants were black and of African origin: 187 were consecutive diabetic patients of whom 81 had ketosis-prone DM-2 and 106 had nonketotic DM-2, and 90 individuals were nondiabetic control participants who were matched for age and sex.Seroprevalence of HHV-8 and percentage of patients with HHV-8 viremia at onset in ketosis-prone DM-2.HHV-8 antibodies were found in 71 patients (87.7%) with ketosis-prone DM-2 vs 16 patients (15.1%) with nonketotic DM-2 (odds ratio, 39.9; 95% confidence interval, 17.1-93.4; P < .001) and 36 of the control participants (40.0%) (odds ratio, 10.7; 95% confidence interval, 4.9-23.4; P < .001). HHV-8 in genomic DNA was present in 6 of 13 patients with ketosis-prone DM-2 tested at acute onset and in 0 of 9 patients with nonketotic DM-2. HHV-8 proteins were present in human islet cells that were cultured for 4 days in the presence of HHV-8.In this preliminary cross-sectional study, the presence of HHV-8 antibodies was associated with ketosis-prone DM-2 in patients of sub-Saharan African origin. Longitudinal studies are required to understand the clinical significance of these findings.
Longitudinal respiratory studies in older people
Authors: J S Milne
Journal: Thorax (1978)

<b>Milne, J S (1978).</b><i>Thorax</i>, <b>33,</b> 547-554. <b>Longitudinal respiratory studies in older people.</b> A random sample of older people in Edinburgh (215 men, 272 women aged 62-90 years) was examined with the MRC questionnaire on respiratory symptoms. The FEV<sub>1</sub> and FVC were recorded. Spirograms were repeated after one and five years and the questions after five years, the sample by then having been reduced to 133 men and 148 women. After five years 7% of the surviving men and women had developed persistent cough and phlegm. This syndrome had disappeared in 12% of men and 2% of women. Dyspnoea had increased beyond grade 2 in 13% of men and 7% of women and had lessened only in 6% of women. One-quarter of male and one-seventh of female cigarette smokers had given up smoking, mostly in the first year. Nearly all who stopped were symptomless before and after. In those men who stopped smoking before the study began symptom prevalence was similar to that in those who continued smoking. Mean values of FEV<sub>1</sub> and FVC declined as age increased, the decline being greater in FVC with resulting rise in FEV<sub>1</sub>%. Five-year differences in FEV<sub>1</sub> and FVC were symmetrically distributed with mean differences increasing with age. Mean differences in FEV<sub>1</sub> were 280-350 ml in men and 150-230 ml in women. Prediction equations from the first examinations remained usable for clinical work. Mean values of FEV<sub>1</sub> and FVC at the first examination were smaller in those who died compared with survivors, whether symptoms were present or not. The prevalence of symptoms was greater in those who died.
Genome-Wide Array Analysis of Normal and Malformed Human Hearts
Authors: Bogac Kaynak, Anja von Heydebreck, Siegrun Mebus, Dominik Seelow, Steffen Hennig, Jan Vogel, Hans-Peter Sperling, Reinhard Pregla, Vladimir Alexi-Meskishvili, Roland Hetzer, Peter E. Lange, Martin Vingron, Hans Lehrach, Silke Sperling
Journal: Circulation (2003)

We present the first genome-wide cDNA array analysis of human congenitally malformed hearts and attempted to partially elucidate these complex phenotypes. Most congenital heart defects, which account for the largest number of birth defects in humans, represent complex genetic disorders. As a consequence of the malformation, abnormal hemodynamic features occur and cause an adaptation process of the heart.The statistical analysis of our data suggests distinct gene expression profiles associated with tetralogy of Fallot, ventricular septal defect, and right ventricular hypertrophy. Applying correspondence analysis, we could associate specific gene functions to specific phenotypes. Furthermore, our study design allows the suggestion that alterations associated with primary genetic abnormalities can be distinguished from those associated with the adaptive response of the heart to the malformation (right ventricular pressure overload hypertrophy). We provide evidence for the molecular transition of the hypertrophic right ventricle to normal left ventricular characteristics. Furthermore, we present data on chamber-specific gene expression.Our findings propose that array analysis of malformed human hearts opens a new window to understand the complex genetic network of cardiac development and adaptation. For detailed access, see the online-only Data Supplement.
Modulation of Longevity and Tissue Homeostasis by the Drosophila PGC-1 Homolog
Authors: Michael Rera, Sepehr Bahadorani, Jaehyoung Cho, Christopher L. Koehler, Matthew Ulgherait, Jae H. Hur, William S. Ansari, Thomas Lo, D. Leanne Jones, David W. Walker
Journal: Cell Metabolism (2011)
The efficacy of aloe vera gel in the treatment of oral lichen planus: a randomized controlled trial
Authors: C. Choonhakarn, P. Busaracome, B. Sripanidkulchai, P. Sarakarn
Journal: British Journal of Dermatology (2007)

Journal Article The efficacy of aloe vera gel in the treatment of oral lichen planus: a randomized controlled trial Get access C. Choonhakarn, C. Choonhakarn Division of Dermatology, Department of Medicine, Srinagarind Hospital Medical School, Faculty of Medicine, *Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences and †Department of Biostatistics and Demography, Faculty of Public Health, Khon Kaen University, Khon Kaen 40002, Thailand Correspondence: Charoen Choonhakarn. E‐mail: c_choonhakarn_dermatologist@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar P. Busaracome, P. Busaracome Division of Dermatology, Department of Medicine, Srinagarind Hospital Medical School, Faculty of Medicine, *Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences and †Department of Biostatistics and Demography, Faculty of Public Health, Khon Kaen University, Khon Kaen 40002, Thailand Search for other works by this author on: Oxford Academic Google Scholar B. Sripanidkulchai, B. Sripanidkulchai Division of Dermatology, Department of Medicine, Srinagarind Hospital Medical School, Faculty of Medicine, *Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences and †Department of Biostatistics and Demography, Faculty of Public Health, Khon Kaen University, Khon Kaen 40002, Thailand Search for other works by this author on: Oxford Academic Google Scholar P. Sarakarn P. Sarakarn Division of Dermatology, Department of Medicine, Srinagarind Hospital Medical School, Faculty of Medicine, *Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences and †Department of Biostatistics and Demography, Faculty of Public Health, Khon Kaen University, Khon Kaen 40002, Thailand Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 158, Issue 3, 1 March 2008, Pages 573–577, https://doi.org/10.1111/j.1365-2133.2007.08370.x Published: 01 March 2008