tbuckley/cabot-search huggingface dataset:
Lifestyle Modification as a Means to Prevent and Treat High Blood Pressure
Authors: Lawrence J. Appel
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. High BP is one of the most important and common risk factors for atherosclerotic cardiovascular disease and renal disease. The contemporary approach to the epidemic of elevated BP and its complications involves pharmacologic treatment of hypertensive individuals and "lifestyle modification," which is beneficial for both nonhypertensive and hypertensive persons. A substantial body of evidence strongly supports the concept that lifestyle modification can have powerful effects on BP. Increased physical activity, a reduced salt intake, weight loss, moderation of alcohol intake, increased potassium intake, and an overall healthy dietary pattern, termed the Dietary Approaches to Stop Hypertension (DASH) diet, effectively lower BP. The DASH diet emphasizes fruits, vegetables, and low-fat dairy products and is reduced in fat and cholesterol. Other dietary factors, such as a greater intake of protein or monounsaturated fatty acids, may also reduce BP but available evidence is inconsistent. The current challenge to health care providers, researchers, government officials, and the general public is developing and implementing effective clinical and public health strategies that lead to sustained lifestyle modification. E-mail: [email protected]
Molecular and functional analysis of occult hepatitis B virus isolates from patients with hepatocellular carcinoma
Authors: Teresa Pollicino, Giuseppina Raffa, Lucy Costantino, Antonella Lisa, Cesare Campello, Giovanni Squadrito, Massimo Levrero, Giovanni Raimondo
Journal: Hepatology (2007)

Occult HBV infection is characterized by the persistence of HBV DNA in the liver of individuals negative for HBV surface antigen (HBsAg). Occult HBV may exist in the hepatocytes as a free genome, although the factors responsible for the very low viral replication and gene expression usually observed in this peculiar kind of infection are mostly unknown. Aims of this study were to investigate whether the viral genomic variability might account for the HBsAg negativity and the inhibition of the viral replication in occult HBV carriers, and to verify in vitro the replication capability of occult HBV strains. We studied liver viral isolates from 17 HBV patients, 13 with occult infection and 4 HBsAg-positive. Full-length HBV genomes from each case were amplified and directly sequenced. Additionally, full-length HBV DNA from eight occult-HBV and two HBsAg-positive cases were cloned and sequenced. Finally, three entire, linear HBV genomes from occult cases were transiently transfected in HuH7 cells. Direct sequencing showed the absence of mutations capable of interfering with viral replication and gene expression in the major viral population of each case. Cloning experiments showed highly divergent HBV strains both in HBsAg-positive and HBsAg-negative individual cases (range of divergence 1.4%-7.1%). All of the 3 transfected full-length HBV isolates showed normal patterns of replication in vitro . Conclusion: Multiple viral variants accumulate in the liver of occult HBV-infected patients. Occult HBV strains are replication-competent in vitro, suggesting that host, rather than viral factors are responsible for cryptic HBV infection.
Rituximab in the spondyloarthropathies: data of eight patients followed up in the French Autoimmunity and Rituximab (AIR) registry: Table 1
Authors: G Nocturne, M Dougados, A Constantin, C Richez, J Sellam, A Simon, D Wendling, X Mariette, J-E Gottenberg
Journal: Annals of the Rheumatic Diseases (2010)

No data are available regarding the safety and efficacy of B-cell depletion in the spondyloarthropathies (SpA), except for two case reports. One patient with ankylosing spondylitis (AS) was prescribed rituximab (RTX) for lymphoma without any improvement of the AS.1 One patient with psoriatic arthritis responded to RTX.2

The French Autoimmunity and Rituximab (AIR) registry, prospectively collects data on patients treated with RTX on- and off-label for refractory arthritides by their clinicians.3 On 23 February 2009, 1383 patients with rheumatoid arthritis, 93 with systemic lupus erythematosus, 43 with primary Sjogren’s syndrome, 55 with vasculitis, 30 with myositis and 112 with other autoimmune or inflammatory diseases, had been included in AIR registry. Among the last group …
The sequential deposition of crystalline material in gallstones: Evidence for changing gallbladder bile composition during the growth of some stones
Authors: D. J. Sutor, S. E. Wooley
Journal: Gut (1974)

Determination of the sequential deposition of crystalline compounds in a representative collection of gallstones from 578 patients has shown that a change in composition of gallstones containing both cholesterol and calcium salt(s) has frequently occurred during growth. Generally a central stone area composed of one of these types of compound is surrounded by outer layers formed of a mixture of both, or vice versa. In a few stones, however, there is a change from one type of compound to the other occurring in successive layers. Both in stones containing cholesterol and calcium salt(s) and in those consisting entirely of calcium salt, there is often also a change in the type of calcium salt present. Such changes provide indirect evidence of changes in gallbladder bile composition during growth of stones, the origin and mechanism of which are not understood.
An International Interpretation Study Using the ALK IHC Antibody D5F3 and a Sensitive Detection Kit Demonstrates High Concordance between ALK IHC and ALK FISH and between Evaluators
Authors: Murry W. Wynes, Lynette M. Sholl, Manfred Dietel, Ed Schuuring, Ming S. Tsao, Yasushi Yatabe, Raymond R. Tubbs, Fred R. Hirsch
Journal: Journal of Thoracic Oncology (2014)
NEXN inhibits GATA4 and leads to atrial septal defects in mice and humans
Authors: Fan Yang, Lei Zhou, Qiguang Wang, Xin You, Ying Li, Yong Zhao, Xiaonan Han, Zai Chang, Xin He, Chunyan Cheng, Chong Wu, Wen-Jing Wang, Fang-Yuan Hu, Ting Zhao, Yang Li, Ming Zhao, Gu-Yan Zheng, Jie Dong, Chun Fan, Juxian Yang, Xianmin Meng, Youyi Zhang, Xianyang Zhu, Jingwei Xiong, Xiao-Li Tian, Huiqing Cao
Journal: Cardiovascular Research (2014)

AimsCardiac structural genes have been implicated as causative factors for congenital heart diseases (CHDs). NEXN is an F-actin binding protein and previously identified as a disease gene causing cardiomyopathies. Whether NEXN contributes to CHDs aetiologically remains unknown. Here, we explored the function of NEXN in cardiac development.
Osmotic Compression of Single Cardiac Myocytes Eliminates the Reduction in Ca <sup>2+</sup> Sensitivity of Tension at Short Sarcomere Length
Authors: Kerry S. McDonald, Richard L. Moss
Journal: Circulation Research (1995)

Abstract According to the Frank-Starling relation, cardiac output varies as a function of end-diastolic volume of the ventricle. The cellular basis of the relation is thought to involve length-dependent variations in Ca 2+ sensitivity of tension; ie, as sarcomere length is increased in cardiac muscle, Ca 2+ sensitivity of tension also increases. One possible explanation for this effect is that the decrease in myocyte diameter as muscle length is increased reduces the lateral spacing between thick and thin filaments, thereby increasing the likelihood of cross-bridge interaction with actin. To examine this idea, we measured the effects of osmotic compression of single skinned cardiac myocytes on Ca 2+ sensitivity of tension. Single myocytes from rat enzymatically digested ventricles were attached to a force transducer and piezoelectric translator, and tension-pCa relations were subsequently characterized at short sarcomere length (SL), at the same short SL in the presence of 2.5% dextran, and at long SL. The pCa (−log[Ca 2+ ]) for half-maximal tension (ie, pCa 50 ) increased from 5.54±0.09 to 5.65±0.10 (n=7, mean±SD, P &lt;.001) as SL was increased from ≈1.85 to ≈2.25 μm. Osmotic compression of myocytes at short length also increased Ca 2+ sensitivity of tension, shifting tension-pCa relations to [Ca 2+ ] levels similar to those observed at long length (pCa 50 , 5.68±0.11). These results support the idea that the length dependence of Ca 2+ sensitivity of tension in cardiac muscle arises in large part from the changes in interfilament lattice spacing that accompany changes in SL.
Risk of perinatal mortality associated with asthma during pregnancy
Authors: M-C Breton, M-F Beauchesne, C Lemiere, E Rey, A Forget, L Blais
Journal: Thorax (2008)

<h3>Background:</h3> Thirteen studies investigating the association between asthma during pregnancy and perinatal mortality reported generally no increased risk. Most of these studies should be interpreted with caution because they were limited in terms of statistical power. A study was therefore undertaken to evaluate whether maternal asthma during pregnancy increases the risk of perinatal mortality. <h3>Methods:</h3> Through three administrative databases from Québec (Canada), a cohort of women with and without asthma who had at least one pregnancy between 1990 and 2002 was formed. Perinatal mortality was identified by diagnostic codes. The adjusted odds ratio (OR) of perinatal mortality in women with and without asthma was compared using Generalised Estimation Equation (GEE) models. The first model included all potential confounders (except small for gestational age, SGA), the second model excluded birth weight, gestational age at birth and SGA and the third model excluded birth weight, gestational age at birth but included only SGA. This analysis was also stratified for birth weight and gestational age at birth. <h3>Results:</h3> The cohort was formed of 13 100 and 28 042 single pregnancies in women with and without asthma. The crude OR of perinatal mortality was 1.35 (95% CI 1.08 to 1.67), which decreased to 0.93 (95% CI 0.75 to 1.17) after adjustment for birth weight and gestational age at birth. Women with asthma had a higher rate of low birthweight babies and preterm delivery than those without asthma. <h3>Conclusion:</h3> The increased risk of low birthweight babies and premature delivery in women with asthma may partly explain the association between maternal asthma and the increased risk of perinatal mortality.
A systematic review of four injection therapies for lateral epicondylosis: prolotherapy, polidocanol, whole blood and platelet-rich plasma
Authors: D Rabago, T M Best, A E Zgierska, E Zeisig, M Ryan, D Crane
Journal: British Journal of Sports Medicine (2008)

To appraise existing evidence for prolotherapy, polidocanol, autologous whole blood and platelet-rich plasma injection therapies for lateral epicondylosis (LE).Systematic review.Medline, Embase, CINAHL, Cochrane Central Register of Controlled Trials, Allied and Complementary Medicine.names and descriptors of the therapies and LE.All human studies assessing the four therapies for LE.Results of five prospective case series and four controlled trials (three prolotherapy, two polidocanol, three autologous whole blood and one platelet-rich plasma) suggest each of the four therapies is effective for LE. In follow-up periods ranging from 9 to 108 weeks, studies reported sustained, statistically significant (p<0.05) improvement in visual analogue scale primary outcome pain score measures and disease-specific questionnaires; relative effect sizes ranged from 51% to 94%; Cohen's d ranged from 0.68 to 6.68. Secondary outcomes also improved, including biomechanical elbow function assessment (polidocanol and prolotherapy), presence of abnormalities and increased vascularity on ultrasound (autologous whole blood and polidocanol). Subjects reported satisfaction with therapies on single-item assessments. All studies were limited by small sample size.There is strong pilot-level evidence supporting the use of prolotherapy, polidocanol, autologous whole blood and platelet-rich plasma injections in the treatment of LE. Rigorous studies of sufficient sample size, assessing these injection therapies using validated clinical, radiological and biomechanical measures, and tissue injury/healing-responsive biomarkers, are needed to determine long-term effectiveness and safety, and whether these techniques can play a definitive role in the management of LE and other tendinopathies.
Effect of anti-ulcer drugs on DNA synthesis in adult normal human hepatocytes in culture*1
Authors: P BLANC
Journal: Hepatology (1995)

The aim of this work was to investigate the effect of four H2 receptor antagonist, cimetidine, ranitidine, famotidine, nizatidine, and of two proton pump inhibitors, omeprazole and lansoprazole, on the mitotic response of human hepatocytes in primary culture. After plating at subconfluent density, cells were exposed to 0.2 to 20 mumol/L of these drugs for 48 hours, either in the absence or in the presence of epidermal growth factor (EGF). The rate of DNA synthesis was evaluated by [3H]-thymidine incorporation into genomic DNA. Both the basal rate of DNA synthesis and the extent of stimulation by EGF exhibited a wide interindividual variability, and were not correlated with the viability of freshly prepared cells. In contrast, the effects of anti-ulcer drugs on the rate of DNA synthesis were clearly reproducible from one culture to another. H2 receptor antagonists had no significant effect (P > .2) over the entire range of concentration tested, whereas omeprazole and lansoprazole significantly inhibited the rate of DNA synthesis by 60% to 90% at 30 mumol/L (P = .016). This effect was concentration dependent between 2 and 20 mumol/L. Neither of the drugs tested was cytotoxic under the conditions used in this work, as assessed by measurements of the do nov protein synthesis. We conclude that, in contrast to H2 receptor antagonists, omeprazole and lansoprazole are able to interfere with the replicative synthesis of DNA in human hepatocytes in culture, at suprapharmacological concentrations. Whether or not this effect is clinically significant remains to be established.
Lipid Lowering by Pravastatin Increases Parasympathetic Modulation of Heart Rate
Authors: C. Michael Welzig, Dong-Gu Shin, Ho-Jin Park, Young-Jo Kim, J. Philip Saul, Jonas B. Galper
Journal: Circulation (2003)

We have previously demonstrated in an in vitro model for lipid lowering that lipoprotein depletion resulted in a marked increase in the negative chronotropic response to the acetylcholine analogue carbamylcholine. In this study we used heart rate variability analysis to determine the effect of lipid lowering by statins on the response of the heart to parasympathetic stimulation. In parallel, we examined whether changes in parasympathetic responsiveness correlated with changes in the expression of Galpha(i2), a molecular component of the parasympathetic signaling pathway in the heart.Patients were randomized in a crossover study of pravastatin and simvastatin. R-R interval analysis of Holter monitor studies demonstrated that in patients treated initially with pravastatin, the peak high-frequency power fraction during sleep, which reflects parasympathetic modulation of heart rate, increased by 24.0+/-5.02% (SEM, n=13, P<0.001) compared with the untreated control value. Simvastatin had no significant effect. Western blot analysis of lymphocytes from patients treated with pravastatin demonstrated a 90.1+/-27.3% (n=10, P=0.009) increase in Galpha(i2) expression, whereas simvastatin had no effect. Relative changes in Galpha(i2) correlated significantly with the changes in the fraction of high-frequency power (rho=0.574, P=0.016).Taken together with our in vitro data, these data are the first to suggest that cholesterol lowering by pravastatin might increase the response of the heart to parasympathetic stimulation and that changes in Galpha(i2) expression might serve as a molecular marker for this effect.
Humoral immune responses against Wilms tumor gene WT1product in patients with hematopoietic malignancies
Authors: Olga A. Elisseeva, Yoshihiro Oka, Akihiro Tsuboi, Kiyoyuki Ogata, Fei Wu, Eui Ho Kim, Toshihiro Soma, Hiroya Tamaki, Manabu Kawakami, Yusuke Oji, Naoki Hosen, Takeshi Kubota, Masashi Nakagawa, Tamotsu Yamagami, Akira Hiraoka, Machiko Tsukaguchi, Keiko Udaka, Hiroyasu Ogawa, Tadamitsu Kishimoto, Taisei Nomura, Haruo Sugiyama
Journal: Blood (2002)
A second-generation screen of the human genome for susceptibility to insulin-dependent diabetes mellitus
Authors: Patrick Concannon, Kathryn J. Gogolin-Ewens, David A. Hinds, Beth Wapelhorst, V. Annem Morrison, Brigid Stirling, Mirna Mitra, Jennifer Farmer, Sloan R. Williams, Nancy J. Cox, Graeme I. Bell, Neil Risch, Richard S. Spielman
Journal: Nature Genetics (1998)
Exertional Hypotension in Cardiac Patients
Authors: ROBERT A. BRUCE, LEONARD A. COBB, SHIGEAKI KATSURA, JOHN H. MORLEDGE, W. WYMAN ANDRUS, THEODORE J. FULLER
Journal: Circulation (1959)

Hemodynamic studies during steady states of sitting and walking on a treadmill have shown a fall in mean arterial pressure in 10 of 16 cardiac patients. This was associated with a greater increase in peripheral resistance during sitting, and a failure to increase stroke index during walking. Cardiac index during exercise increased somewhat, largely because of greater acceleration of heart rate.
Acute hepatic and renal toxicity from low doses of acetaminophen in the absence of alcohol abuse or malnutrition: Evidence for increased susceptibility to drug toxicity due to cardiopulmonary and renal insufficiency
Authors: Herbert L. Bonkovsky, Robert E. Kane, Dean P. Jones, Raymond E. Galinsky, Barbara Banner
Journal: Hepatology (1994)

A 67-yr-old man with chronic cardiopulmonary disease exhibited severe hepatic and moderately severe renal injury after short-term ingestion of therapeutic doses of acetaminophen (1 to 3 gm/day for 3 days). Drug metabolism and other studies, performed 5 mo after recovery from the acute insult, indicated that the patient had decreased rates of hepatic metabolism of acetaminophen to its primary, nontoxic metabolites and decreased kidney function that was compromised further by acetaminophen ingestion. He also had abnormally low concentrations of hepatic and plasma reduced glutathione. Alcohol abuse and malnutrition could not be implicated in the pathogenesis of injury; rather it appeared that advancing age with chronic renal, cardiac and pulmonary insufficiency contributed to acetaminophen toxicity in this patient.
Dietary composition modulates brain mass and solubilizable Aβ levels in a mouse model of aggressive Alzheimer's amyloid pathology
Authors: Steve Pedrini, Carlos Thomas, Hannah Brautigam, James Schmeidler, Lap Ho, Paul Fraser, David Westaway, Peter StGeorge Hyslop, Ralph N Martins, Joseph D Buxbaum, Giulio M Pasinetti, Dara L Dickstein, Patrick R Hof, Michelle E Ehrlich, Sam Gandy
Journal: Molecular Neurodegeneration (2009)

Alzheimer's disease (AD) is a progressive neurodegenerative disease of the central nervous system (CNS). Recently, an increased interest in the role diet plays in the pathology of AD has resulted in a focus on the detrimental effects of diets high in cholesterol and fat and the beneficial effects of caloric restriction. The current study examines how dietary composition modulates cerebral amyloidosis and neuronal integrity in the TgCRND8 mouse model of AD.From 4 wks until 18 wks of age, male and female TgCRND8 mice were maintained on one of four diets: (1) reference (regular) commercial chow; (2) high fat/low carbohydrate custom chow (60 kcal% fat/30 kcal% protein/10 kcal% carbohydrate); (3) high protein/low carbohydrate custom chow (60 kcal% protein/30 kcal% fat/10 kcal% carbohydrate); or (4) high carbohydrate/low fat custom chow (60 kcal% carbohydrate/30 kcal% protein/10 kcal% fat). At age 18 wks, mice were sacrificed, and brains studied for (a) wet weight; (b) solubilizable Abeta content by ELISA; (c) amyloid plaque burden; (d) stereologic analysis of selected hippocampal subregions.Animals receiving a high fat diet showed increased brain levels of solubilizable Abeta, although we detected no effect on plaque burden. Unexpectedly, brains of mice fed a high protein/low carbohydrate diet were 5% lower in weight than brains from all other mice. In an effort to identify regions that might link loss of brain mass to cognitive function, we studied neuronal density and volume in hippocampal subregions. Neuronal density and volume in the hippocampal CA3 region of TgCRND8 mice tended to be lower in TgCRND8 mice receiving the high protein/low carbohydrate diet than in those receiving the regular chow. Neuronal density and volume were preserved in CA1 and in the dentate gyrus.Dissociation of Abeta changes from brain mass changes raises the possibility that diet plays a role not only in modulating amyloidosis but also in modulating neuronal vulnerability. However, in the absence of a study of the effects of a high protein/low carbohydrate diet on nontransgenic mice, one cannot be certain how much, if any, of the loss of brain mass exhibited by high protein/low carbohydrate diet-fed TgCRND8 mice was due to an interaction between cerebral amyloidosis and diet. Given the recent evidence that certain factors favor the maintenance of cognitive function in the face of substantial structural neuropathology, we propose that there might also exist factors that sensitize brain neurons to some forms of neurotoxicity, including, perhaps, amyloid neurotoxicity. Identification of these factors could help reconcile the poor clinicopathological correlation between cognitive status and structural neuropathology, including amyloid pathology.
Folate-Conjugated Rapamycin Slows Progression of Polycystic Kidney Disease
Authors: Jonathan M. Shillingford, Christopher P. Leamon, Iontcho R. Vlahov, Thomas Weimbs
Journal: Journal of the American Society of Nephrology (2012)

Activation of the mammalian target of rapamycin (mTOR) signaling pathway is aberrant in autosomal-dominant polycystic kidney disease (ADPKD). The mTOR inhibitors, such as rapamycin, ameliorate PKD in rodent models, but clinical trials have not shown benefit, possibly as a result of low tissue concentrations of rapamycin at clinically tolerable doses. To overcome this limitation, we synthesized a folate-conjugated form of rapamycin (FC-rapa) that is taken up by folate receptor–mediated endocytosis and cleaved intracellularly to reconstitute the active drug. We found that renal cyst-lining cells highly express the folate receptor in ADPKD and mouse models. In vitro, FC-rapa inhibited mTOR activity in a dose- and folate receptor–dependent manner. Treatment of a PKD mouse model with FC-rapa inhibited mTOR in the target tissue, strongly attenuated proliferation and growth of renal cysts and preserved renal function. Furthermore, FC-rapa inhibited mTOR activity in the kidney but not in other organs. In summary, these results suggest that targeting the kidney using FC-rapa may overcome the significant side effects and lack of renal efficacy observed in clinical trials with mTOR inhibitors in ADPKD.