tbuckley/cabot-search huggingface dataset:
Hepatoprotection by the farnesoid X receptor agonist GW4064 in rat models of intra- and extrahepatic cholestasis
Authors: Yaping Liu, Jane Binz, Mary Jo Numerick, Steve Dennis, Guizhen Luo, Bhasha Desai, Kathleen I. MacKenzie, Traci A. Mansfield, Steven A. Kliewer, Bryan Goodwin, Stacey A. Jones
Journal: Journal of Clinical Investigation (2003)

Farnesoid X receptor (FXR) is a bile acid-activated transcription factor that is a member of the nuclear hormone receptor superfamily. Fxr-null mice exhibit a phenotype similar to Byler disease, an inherited cholestatic liver disorder. In the liver, activation of FXR induces transcription of transporter genes involved in promoting bile acid clearance and represses genes involved in bile acid biosynthesis. We investigated whether the synthetic FXR agonist GW4064 could protect against cholestatic liver damage in rat models of extrahepatic and intrahepatic cholestasis. In the bile duct-ligation and alpha-naphthylisothiocyanate models of cholestasis, GW4064 treatment resulted in significant reductions in serum alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase, as well as other markers of liver damage. Rats that received GW4064 treatment also had decreased incidence and extent of necrosis, decreased inflammatory cell infiltration, and decreased bile duct proliferation. Analysis of gene expression in livers from GW4064-treated cholestatic rats revealed decreased expression of bile acid biosynthetic genes and increased expression of genes involved in bile acid transport, including the phospholipid flippase MDR2. The hepatoprotection seen in these animal models by the synthetic FXR agonist suggests FXR agonists may be useful in the treatment of cholestatic liver disease.
Asymmetric dimethylarginine and hemodynamic regulation in middle-aged men
Authors: Hannu Päivä, Juha Laakso, Mika Kähönen, Väinö Turjanmaa, Tiit Kööbi, Silja Majahalme, Terho Lehtimäki, Inkeri Ruokonen, Reijo Laaksonen
Journal: Metabolism (2006)
Anti-androgen treatment in women with acne: a controlled trial
Authors: J.A. MILLER, FENELLA T. WOJNAROWSKA, PAULINE M. DOWD, R.E. ASHTON, T.J. O'BRIEN, W.A.D. GRIFFITHS, H.S. JACOBS
Journal: British Journal of Dermatology (1986)

Ninety female patients with acne were allocated randomly to one of three groups and treated either with Diane, a high dose cyproterone acetate (CPA) regime with ethinyloestradiol, or Minovlar. The same dose of oestrogen was common to all three treatment groups. Patients were assessed every 2 months for 6 months, by grading for severity of the acne, lesion counts and photography, and subjectively using a visual analogue scale. In addition, bacteriological sampling and sebum excretion rate (SER) measurements were performed. The results showed a clinical improvement in all three treatment groups, but a more rapid and complete response was seen in those groups who received CPA. There was also a consistent trend suggesting a more favourable response in those in the high dose CPA group. Although there was a marked reduction in SER in the groups treated with CPA, there was no correlation between reduction in SER and clinical improvement in individuals, nor could a reduction in the surface bacterial population be shown to be a primary event in the success of anti-androgen therapy. We have shown that the addition of CPA to oestrogen adds significantly to the therapeutic effect in acne and that anti-androgen and oestrogen combinations are more effective than standard oestrogen and progestagen contraceptive pills.
Hemoglobin A1c Levels and Mortality in the Diabetic Hemodialysis Population
Authors: Sylvia Paz B. Ramirez, Keith P. McCullough, Jyothi R. Thumma, Robert G. Nelson, Hal Morgenstern, Brenda W. Gillespie, Masaaki Inaba, Stefan H. Jacobson, Raymond Vanholder, Ronald L. Pisoni, Fritz K. Port, Bruce M. Robinson
Journal: Diabetes Care (2012)

OBJECTIVE Lowering hemoglobin A1c to &amp;lt;7% reduces the risk of microvascular complications of diabetes, but the importance of maintaining this target in diabetes patients with kidney failure is unclear. We evaluated the relationship between A1c levels and mortality in an international prospective cohort study of hemodialysis patients. RESEARCH DESIGN AND METHODS Included were 9,201 hemodialysis patients from 12 countries (Dialysis Outcomes and Practice Patterns Study 3 and 4, 2006–2010) with type 1 or type 2 diabetes and at least one A1c measurement during the first 8 months after study entry. Associations between A1c and mortality were assessed with Cox regression, adjusting for potential confounders. RESULTS The association between A1c and mortality was U-shaped. Compared with an A1c of 7–7.9%, the hazard ratios (95% CI) for A1c levels were 1.35 (1.09–1.67) for &amp;lt;5%, 1.18 (1.01–1.37) for 5–5.9%, 1.21 (1.05–1.41) for 6–6.9%, 1.16 (0.94–1.43) for 8–8.9%, and 1.38 (1.11–1.71) for ≥9.0%, after adjustment for age, sex, race, BMI, serum albumin, years of dialysis, serum creatinine, 12 comorbid conditions, insulin use, hemoglobin, LDL cholesterol, country, and study phase. Diabetes medications were prescribed for 35% of patients with A1c &amp;lt;6% and not prescribed for 29% of those with A1c ≥9%. CONCLUSIONS A1c levels strongly predicted mortality in hemodialysis patients with type 1 or type 2 diabetes. Mortality increased as A1c moved further from 7–7.9%; thus, target A1c in hemodialysis patients may encompass values higher than those recommended by current guidelines. Modifying glucose-lowering medicines for dialysis patients to target A1c levels within this range may be a modifiable practice to improve outcomes.
The origin and evolution of green algal and plant actins
Authors: S. S. An, B. Mopps, K. Weber, D. Bhattacharya
Journal: Molecular Biology and Evolution (1999)

The Viridiplantae are subdivided into two groups: the Chlorophyta, which includes the Chlorophyceae, Trebouxiophyceae, Ulvophyceae, and Prasinophyceae; and the Streptophyta, which includes the Charophyceae and all land plants. Within the Streptophyta, the actin genes of the angiosperms diverge nearly simultaneously from each other before the separation of monocots and dicots. Previous evolutionary analyses have provided limited insights into the gene duplications that have produced these complex gene families. We address the origin and diversification of land plant actin genes by studying the phylogeny of actins within the green algae, ferns, and fern allies. Partial genomic sequences or cDNAs encoding actin were characterized from Cosmarium botrytis (Zygnematales), Selaginella apoda (Selaginellales), Anemia phyllitidis (Polypodiales), and Psilotum triquetrum (Psilotales). Selaginella contains at least two actin genes. One sequence (Ac2) diverges within a group of fern sequences that also includes the Psilotum Ac1 actin gene and one gymnosperm sequence (Cycas revoluta Cyc3). This clade is positioned outside of the angiosperm actin gene radiation. The second Selaginella sequence (Ac1) is the sister to all remaining land plant actin sequences, although the internal branches in this portion of the tree are very short. Use of complete actin-coding regions in phylogenetic analyses provides support for the separation of angiosperm actins into two classes. N-terminal "signature" sequence analyses support these groupings. One class (VEG) includes actin genes that are often expressed in vegetative structures. The second class (REP) includes actin genes that trace their ancestry within the vegetative actins and contains members that are largely expressed in reproductive structures. Analysis of intron positions within actin genes shows that sequences from both Selaginella and Cosmarium contain the conserved 20-3, 152-1, and 356-3 introns found in many members of the Streptophyta. In addition, the Cosmarium actin gene contains a novel intron at position 76-1.
Survival After Mitral Valve Replacement
Authors: R. Morton Bolman
Journal: Circulation (2007)

he surgical replacement of diseased heart valves is based on the premise that the prosthesis chosen to replace a stenotic or insufficient valve will have a beneficial impact on the patient's heart function, taking into account the risks of surgery and the recognized complications of prosthetic heart valves.It is well established that mitral valve replacement (MVR) is associated with higher shortand long-term mortality than mitral valve repair. 1,2Although the exact mechanism for this discrepancy is unknown, it increases the importance of repairing valves whenever possible and, when MVR is necessary, intervening to prevent prosthesis-and/or patient-related factors that may lead to less favorable postoperative outcomes. Article p 1417A growing literature has identified aortic valve patientprosthesis mismatch (PPM) after aortic valve replacement.Studies have suggested that aortic PPM may be accompanied by lower rates and absolute degree of regression of left ventricular hypertrophy.4][5][6][7] This linkage is controversial, however; other authors suggest that PPM is of less importance after aortic valve replacement and indeed that valve size may not matter. 8Many fewer data are available regarding PPM after MVR.In this issue of Circulation, Magne et al 9 investigate the impact of PPM on survival after MVR.The authors hypothesize that the effective orifice area (EOA) of prosthetic valves is often small relative to the patient's size, thus causing a mismatch between valve EOA and flow across the valve.As a result, seemingly normally functioning mitral prostheses often have relatively high transvalvular gradients.These gradients mimic those found in patients with mitral stenosis.In addition to delaying the regression of left atrial and pulmonary artery hypertension, these high gradients and the resulting high left atrial pressures may lead to atrial dilation and subsequent atrial fibrillation.This same group recently published a study
WHAT IS THE EVIDENCE OF TROCHLEOPLASTY IN TREATMENT OF PATELLOFEMORAL INSTABILITY? A SYSTEMATIC REVIEW AND COMPARISON WITH MPFL RECONSTRUCTION OUTCOMES
Authors: Enrique Adrian Testa, Felix Amsler, Carlo Camathias, Philipp Henle, Niklaus Friederich, Michael Tobias Hirschmann
Journal: British Journal of Sports Medicine (2013)

Introduction Trochleoplasty and reconstruction of the medial patellofemoral ligament (MPFL) are the most commonly used surgical treatment in patients with patellofemoral instability. Although there is an increasing number of publications dealing with treatment of patellofemoral instability, the clinical evidence about outcomes and in particular the question when to use which method is still scarce. It was our purpose to perform a systematic review on trochleoplasty in the treatment of patients with patellofemoral instability and compare the outcomes with those seen in patients treated by reconstruction of the MPFL. Methods Two independent orthopaedic surgeons performed a standardized search on Pubmed and other literature search engines and reviewed the obtained abstracts. All observational and experimental studies (case reports excluded) were then obtained in fulltext and again reviewed in a consensus meeting. 15 articles were included and analysed using the PEDro appraisal scoring system to assess its methodological quality. As comparison group the same process was done for MPFL reconstruction. 25 studies on MPFL reconstruction were obtained for comparison. The clinical and radiological outcomes of all papers was reviewed and compared. The studies investigated use a great variety of different outcome scoring instruments. Seven outcome variables were found consistently in most of the studies. Descriptive statistics was used for comparison of Kujala score, Lysholm score, patella tilt angle (PTA), sulcus angle (SA), apprehension test, redislocation and instability rates. Results There was no statistical significant difference in outcomes between both groups investigated. The MPFL reconstruction group showed a trend to better clinical outcomes. Mean postoperative Kujala score and Lysholm score increased significantly in both groups when compared to preoperatively (Kujala:61.4 to 80.8 and 46.9 to 88.8; Lysholm:55.5 to 78.5 and 59.9 to 91.1). Postoperatively a positive apprehension test was found in 8% of the MPFL group and in 20% of Trochleoplasty group. No difference in redislocation (2%) and instability (5–6%) rates between both groups. Mean PTA and SA showed a decrease in the trochleoplasty group (PTA: 30° to 15.9° and 12.6° to 8.1°, SA: 145.5° to 135.7° and 149° to 145.6°). Conclusion Considering all limitations this systematic review showed that trochleoplasty and MPFL reconstruction are able to deliver good clinical outcomes with stable patellofemoral joints. The minor differences in outcomes seem to be related to different patient populations and surgical techniques.
MENTAL DETERIORATION AND DEFICIENCY
Authors: Temple Fay
Journal: American Journal of Psychiatry (1933)

Various groups of acute and subacute cerebral problems associated with mental deterioration have been presented, and the method of management indicated, which has been associated with arresting of the mental deterioration or with actual improvement in many cases where effectual cooperation and demonstrable dehydration have been accomplished. That the results may indicate a possible line of approach in the more chronic type is suggested, as well as the need for preventive measures instituted along the lines of disturbed fluid metabolism of the body. This requires careful consideration in the management of such problems before profound states of deterioration have occurred.
Association of Long QT Syndrome Loci and Cardiac Events Among Patients Treated With β-Blockers
Authors: Silvia G. Priori
Journal: JAMA (2004)

ContextData on the efficacy of β-blockers in the 3 most common genetic long QT syndrome (LQTS) loci are limited.ObjectiveTo describe and assess outcome in a large systematically genotyped population of β-blocker–treated LQTS patients.Design, Setting, and PatientsConsecutive LQTS-genotyped patients (n = 335) in Italy treated with β-blockers for an average of 5 years.Main Outcome MeasuresCardiac events (syncope, ventricular tachycardia/torsades de pointes, cardiac arrest, and sudden cardiac death) while patients received β-blocker therapy according to genotype.ResultsCardiac events among patients receiving β-blocker therapy occurred in 19 of 187 (10%) LQT1 patients, 27 of 120 (23%) LQT2 patients, and 9 of 28 (32%) LQT3 patients (P<.001). The risk of cardiac events was higher among LQT2 (adjusted relative risk, 2.81; 95% confidence interval [CI], 1.50-5.27; P = .001) and LQT3 (adjusted relative risk, 4.00; 95% CI, 2.45-8.03; P<.001) patients than among LQT1 patients, suggesting inadequate protection from β-blocker therapy. Other important predictors of risk were a QT interval corrected for heart rate that was more than 500 ms in patients receiving therapy (adjusted relative risk, 2.01; 95% CI, 1.16-3.51; P = .01) and occurrence of a first cardiac event before the age of 7 years (adjusted RR, 4.34; 95% CI, 2.35-8.03; P<.001).ConclusionAmong patients with genetic LQTS treated with β-blockers, there is a high rate of cardiac events, particularly among patients with LQT2 and LQT3 genotypes.
Factor interaction analysis for chromosome 8 and DNA methylation alterations highlights innate immune response suppression and cytoskeletal changes in prostate cancer.
Authors: Wolfgang A Schulz, Adrian Alexa, Volker Jung, Christiane Hader, Michèle J Hoffmann, Masanori Yamanaka, Sandy Fritzsche, Agnes Wlazlinski, Mirko Müller, Thomas Lengauer, Rainer Engers, Andrea R Florl, Bernd Wullich, Jörg Rahnenführer
Journal: Molecular Cancer (2007)

Alterations of chromosome 8 and hypomethylation of LINE-1 retrotransposons are common alterations in advanced prostate carcinoma. In a former study including many metastatic cases, they strongly correlated with each other. To elucidate a possible interaction between the two alterations, we investigated their relationship in less advanced prostate cancers. In 50 primary tumor tissues, no correlation was observed between chromosome 8 alterations determined by comparative genomic hybridization and LINE-1 hypomethylation measured by Southern blot hybridization. The discrepancy towards the former study, which had been dominated by advanced stage cases, suggests that both alterations converge and interact during prostate cancer progression. Therefore, interaction analysis was performed on microarray-based expression profiles of cancers harboring both alterations, only one, or none. Application of a novel bioinformatic method identified Gene Ontology (GO) groups related to innate immunity, cytoskeletal organization and cell adhesion as common targets of both alterations. Many genes targeted by their interaction were involved in type I and II interferon signaling and several were functionally related to hereditary prostate cancer genes. In addition, the interaction appeared to influence a switch in the expression pattern of EPB41L genes encoding 4.1 cytoskeleton proteins. Real-time RT-PCR revealed GADD45A, MX1, EPB41L3/DAL1, and FBLN1 as generally downregulated in prostate cancer, whereas HOXB13 and EPB41L4B were upregulated. TLR3 was downregulated in a subset of the cases and associated with recurrence. Downregulation of EPB41L3, but not of GADD45A, was associated with promoter hypermethylation, which was detected in 79% of carcinoma samples. Alterations of chromosome 8 and DNA hypomethylation in prostate cancer probably do not cause each other, but converge during progression. The present analysis implicates their interaction in innate immune response suppression and cytoskeletal changes during prostate cancer progression. The study thus highlights novel mechanisms in prostate cancer progression and identifies novel candidate genes for diagnostic and therapeutic purposes. In particular, TLR3 expression might be useful for prostate cancer prognosis and EPB41L3 hypermethylation for its detection.
Sulindac Enhances the Proteasome Inhibitor Bortezomib-Mediated Oxidative Stress and Anticancer Activity
Authors: Takae Minami, Masaaki Adachi, Rina Kawamura, Yubin Zhang, Yasuhisa Shinomura, Kohzoh Imai
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The nonsteroidal antiinflammatory drug sulindac is a promising chemopreventive agent against colon cancer. Here, we address whether sulindac enhances the anticancer effects of the proteasome inhibitor bortezomib (PS-341) in colon cancer cells. Experimental Design: The synergistic effects of sulindac with bortezomib were evaluated by cell death, colony formation assay, DNA fragmentation, and tumor progression of DLD-1 xenografts. Reactive oxygen species (ROS) generation was detected using carboxy-H2DCFDA or dihydroethidium. Oxidative stress was evaluated by heme oxygenase-1 induction and stress-activated mitogen-activated protein kinases p38 and c-Jun-NH2-kinase phosphorylation. Oxidative DNA damage was evaluated by histone H2AX phosphorylation and accumulation of 8-hydroxy-2′-deoxyguanosine. Results: Sulindac and its metabolites enhanced the anticancer effects of bortezomib in DLD-1 and BM314 colon cancer cells. Sulindac induced ROS generation and enhanced bortezomib-mediated oxidative stress and subsequent DNA damage. Their combined effects were highly sensitive to free radical scavengers l-N-acetylcysteine and α-tocopherol, but were much less sensitive to a p38 inhibitor SB203580. Conclusion: Sulindac synergistically augments the anticancer effects of bortezomib primarily through cooperative ROS generation and oxidative DNA damage, thereby representing a novel combination therapy against colon cancer.
Spatial Analysis of the Relationship between Mortality from Cardiovascular and Cerebrovascular Disease and Drinking Water Hardness
Authors: Juan Ferrándiz, Juan J. Abellán, Virgilio Gómez-Rubio, Antonio López-Quílez, Pilar Sanmartín, Carlos Abellán, Miguel A. Martínez-Beneito, Inmaculada Melchor, Hermelinda Vanaclocha, Óscar Zurriaga, Ferrán Ballester, José M. Gil, Santiago Pérez-Hoyos, Ricardo Ocaña
Journal: Environmental Health Perspectives (2004)

Previously published scientific papers have reported a negative correlation between drinking water hardness and cardiovascular mortality. Some ecologic and case–control studies suggest the protective effect of calcium and magnesium concentration in drinking water. In this article we present an analysis of this protective relationship in 538 municipalities of Comunidad Valenciana (Spain) from 1991–1998. We used the Spanish version of the Rapid Inquiry Facility (RIF) developed under the European Environment and Health Information System (EUROHEIS) research project. The strategy of analysis used in our study conforms to the exploratory nature of the RIF that is used as a tool to obtain quick and flexible insight into epidemiologic surveillance problems. This article describes the use of the RIF to explore possible associations between disease indicators and environmental factors. We used exposure analysis to assess the effect of both protective factors—calcium and magnesium—on mortality from cerebrovascular (ICD-9 430–438) and ischemic heart (ICD-9 410–414) diseases. This study provides statistical evidence of the relationship between mortality from cardiovascular diseases and hardness of drinking water. This relationship is stronger in cerebrovascular disease than in ischemic heart disease, is more pronounced for women than for men, and is more apparent with magnesium than with calcium concentration levels. Nevertheless, the protective nature of these two factors is not clearly established. Our results suggest the possibility of protectiveness but cannot be claimed as conclusive. The weak effects of these covariates make it difficult to separate them from the influence of socioeconomic and environmental factors. We have also performed disease mapping of standardized mortality ratios to detect clusters of municipalities with high risk. Further standardization by levels of calcium and magnesium in drinking water shows changes in the maps when we remove the effect of these covariates.
Short-Term Effects of Right-Left Heart Sequential Cardiac Resynchronization in Patients With Heart Failure, Chronic Atrial Fibrillation, and Atrioventricular Nodal Block
Authors: Ilan Hay, Vojtech Melenovsky, Barry J. Fetics, Daniel P. Judge, Andrew Kramer, Julio Spinelli, Craig Reister, David A. Kass, Ronald D. Berger
Journal: Circulation (2004)

Background— Single-site ventricular pacing in patients with heart failure, atrial fibrillation, and severe atrioventricular (AV) nodal block risks the generation of discoordinate contraction. Whether altering the site of stimulation can offset this detrimental effect and what role sequential right ventricular–left ventricular (RV-LV) stimulation might play in such patients remain unknown. Methods and Results— Nine subjects with heart failure (ejection fraction, 14% to 30%), atrial fibrillation, and AV block were studied by pressure-volume analysis. Ventricular stimulation was applied to the RV (apex and outflow tract), LV free wall, and biventricular (BiV) at 80 and 120 bpm. BiV improved systolic function more than either site alone (dP/dt max , 810±83, 924±98, 983±102 mm Hg/s for RV, LV, BiV, respectively; P &lt;0.05), although LV pacing was significantly better than RV pacing. However, only BiV improved diastolic function (isovolumic relaxation) over RV or LV alone. Similar results were obtained for both heart rates. RV pacing site did not alter the BiV effect, and concomitant stimulation of both RV sites did not improve function over each alone. Finally, varying RV-LV delay revealed optimal responses with simultaneous pacing. Conclusions— Simultaneous BiV pacing acutely enhances both systolic and diastolic function over single-site RV or LV pacing in congestive heart failure patients with atrial fibrillation and advanced AV block. Sequential RV-LV stimulation offers minimal benefit on average and should perhaps be considered only in targeted subsets such as nonresponding patients.