tbuckley/cabot-search huggingface dataset:
Hepatic arterial buffer response in patients with advanced cirrhosis
Authors: Veit Gülberg, Klaus Haag, Martin Rössle, Alexander L. Gerbes
Journal: Hepatology (2002)

Hepatic arterial buffer response (HABR) is considered an important compensatory mechanism to maintain perfusion of the liver by hepatic arterial vasodilation on reduction of portal venous perfusion. HABR has been suggested to be impaired in patients with advanced cirrhosis. In patients with hepatopetal portal flow, placement of a transjugular intrahepatic portosystemic shunt (TIPS) reduces portal venous liver perfusion. Accordingly, patients with severe cirrhosis should have impaired HABR after TIPS implantation. Therefore, the aim of this study was to investigate the effect of TIPS on HABR as reflected by changes in resistance index (RI) of the hepatic artery. A total of 366 patients with cirrhosis (Child-Pugh class A, 106; class B, 168; class C, 92) underwent duplex Doppler ultrasonographic examination with determination of RI and maximal flow velocity in the portal vein before and 1 month after TIPS placement. Portosystemic pressure gradient was determined before and after TIPS placement. In 29 patients with hepatofugal portal blood flow, RI was significantly lower than in 337 patients with hepatopetal flow (0.63 plus minus 0.02 vs. 0.69 plus minus 0.01; P <.001). TIPS induced a significant decrease of the RI in patients with hepatopetal flow (RI, 0.69 plus minus 0.01 before vs. 0.64 plus minus 0.01 after TIPS; P =.001) but not in patients with hepatofugal flow (RI, 0.63 plus minus 0.02 before vs. 0.63 plus minus 0.02 after TIPS; NS). This response was not dependent on the Child-Pugh class. In conclusion, our results suggest that some degree of HABR is preserved even in patients with advanced cirrhosis with significant portal hypertension.
Exogenous amino acids stimulate net muscle protein synthesis in the elderly.
Authors: E Volpi, A A Ferrando, C W Yeckel, K D Tipton, R R Wolfe
Journal: Journal of Clinical Investigation (1998)

We have investigated the response of amino acid transport and protein synthesis in healthy elderly individuals (age 71+/-2 yr) to the stimulatory effect of increased amino acid availability. Muscle protein synthesis and breakdown, and amino acid transport were measured in the postabsorptive state and during the intravenous infusion of an amino acid mixture. Muscle-free amino acid kinetics were calculated by means of a three compartment model using data obtained by femoral arterio-venous catheterization and muscle biopsies from the vastus lateralis during the infusion of stable isotope tracers of amino acids. In addition, muscle protein fractional synthetic rate (FSR) was measured. Peripheral amino acid infusion significantly increased amino acid delivery to the leg, amino acid transport, and muscle protein synthesis when measured either with the three compartment model (P < 0.05) or with the traditional precursor-product approach (FSR increased from 0. 0474+/-0.0054 to 0.0940+/-0.0143%/h, P < 0.05). Because protein breakdown did not change during amino acid infusion, a positive net balance of amino acids across the muscle was achieved. We conclude that, although muscle mass is decreased in the elderly, muscle protein anabolism can nonetheless be stimulated by increased amino acid availability. We thus hypothesize that muscle mass could be better maintained with an increased intake of protein or amino acids.
A genetic variant in the region of<i>MMP-9</i>is associated with serum levels and progression of joint damage in rheumatoid arthritis
Authors: D P C de Rooy, A Zhernakova, R Tsonaka, A Willemze, B A S Kurreeman, G Trynka, L van Toorn, R E M Toes, T W J Huizinga, J J Houwing-Duistermaat, P K Gregersen, A H M van der Helm-van Mil
Journal: Annals of the Rheumatic Diseases (2013)

The severity of joint destruction is highly variable between rheumatoid arthritis (RA) patients. The majority of its heritability is still unexplained. Several autoimmune diseases share genetic risk variants that may also influence disease progression. We aimed to identify genetic risk factors for the severity of joint damage in RA by studying genetic susceptibility loci of several autoimmune diseases.
The breathless adolescent asthmatic athlete
Authors: K-H. Carlsen
Journal: European Respiratory Journal (2011)

This article concerns physical activity and sports in asthmatic adolescents. Exercise-induced asthma (EIA) is found in 8–10% of the normal child population and in ∼35% of children with current asthma, as reported in a population-based birth cohort study. The mechanisms of EIA are related to markedly increased ventilation during exercise, which causes increased heat and water loss through respiration, leading to bronchial constriction. In athletes and especially in endurance athletes, the repeated daily physical activity during training will, over time, cause epithelial damage and increase inflammation in the respiratory mucosa. With increased exposure to environmental agents, such as as cold air in skiers and chlorine compounds in swimmers, the athlete may contract symptoms and signs of asthma and bronchial hyperresponsiveness, either worsening existing asthma or causing symptoms in a previous healthy adolescent athlete. There are several causes of breathlessness in adolescents, including EIA, vocal cord dysfunction, poor physical fitness and others, which are important to consider in the diagnostic procedure. The asthmatic athlete should follow the same guidelines for treating their asthma as an ordinary asthmatic patient, with careful consideration of the special diagnostic rules given for the use of asthma drugs in sports, especially for inhaled β 2 -agonists.
E1A, E1B Double-Restricted Adenovirus with RGD-Fiber Modification Exhibits Enhanced Oncolysis for CAR–Deficient Biliary Cancers
Authors: Mariko Wakayama, Masato Abei, Rei Kawashima, Emiko Seo, Kuniaki Fukuda, Hideo Ugai, Takehide Murata, Naomi Tanaka, Ichinosuke Hyodo, Hirofumi Hamada, Kazunari K. Yokoyama
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Cancers of biliary system represent highly malignant diseases of dismal prognosis. We have previously introduced AxdAdB3, an E1A, E1B double-restricted oncolytic adenovirus, which showed excellent oncolytic efficacy for approximately half of the biliary cancer lines with an enhanced safety to normal cells. The purpose of this study was to evaluate whether RGD-fiber modification (AxdAdB3-F/RGD), which enables integrin-dependent infection, can improve the infectivity and efficacy of AxdAdB3 for biliary cancers. Experimental Design: Expressions of adenoviral receptors, coxsackievirus adenovirus receptor (CAR) and integrins (αvβ3 and αvβ5), were compared with the level of infectivity of LacZ-expressing replication-defective adenoviruses with wild-type fibers or RGD-modified fibers in a panel of biliary cancer cell lines in vitro. Viral replication and cytotoxicity in vitro of AxdAdB3-F/RGD, a novel E1A, E1B double-restricted replication-selective adenovirus with RGD-modified fibers, were compared with those of its parent virus, AxdAdB3, in various biliary cancer cells and in normal cells. In vivo antitumor effects of these oncolytic viruses were compared in a xenograft tumor model. Results: Expression of CAR significantly correlated with the adenovirus infectivity, whereas integrin αvβ5 was abundantly expressed in almost all biliary cancer cells. Whereas AxdAdB3 effectively replicated and lysed only the biliary cancer cells with a preserved expression of CAR, AxdAdB3-F/RGD exhibited efficient replication and potent oncolysis in both CAR-positive and CAR-negative biliary cancer cells. AxdAdB3-F/RGD showed attenuated replication and little cytopathy in human normal cells (i.e., hepatocytes, WI-38 cells) as well as AxdAdB3. Furthermore, in nude mice with s.c. xenografts of CAR-deficient human biliary cancer, i.t. AxdAdB3-F/RGD therapy caused a marked inhibition of tumor growth. Conclusions: The RGD-fiber modification strategy enhanced the infectivity, replication, and oncolytic effects of the E1A, E1B double-restricted oncolytic adenovirus for CAR-deficient biliary cancers. In addition, it preserved the merit of excellent safety of the double-restricted virus for normal cells. These results suggest a potential use of this agent for the treatment of biliary cancers.
Prevalence and Determinants of Glucose Intolerance in a Dutch Caucasian Population: The Hoorn Study
Authors: Johanna M Mooy, Peter A Grootenhuis, Hendrik de Vries, Hans A Valkenburg, Lex M Bouter, Pieter J Kostense, Robert J Heine
Journal: Diabetes Care (1995)

OBJECTIVE To study the prevalence and determinants of glucose intolerance in a general Caucasian population. RESEARCH DESIGN AND METHODS A random sample of 50- to 74-year old Caucasians (n = 2,484) underwent oral glucose tolerance tests. Multiple regression analyses were performed to study the association of 2-h postload plasma glucose values with potential determinants. RESULTS Prevalence of known and newly detected diabetes and impaired glucose tolerance was 3.6, 4.8, and 10.3%, respectively. In women, but not in men, the association of body mass index with 2-h glucose was fully accounted for by the waist-to-hip ratio. Maternal history of diabetes was twice as prevalent as paternal history, but paternal history only was associated with 2-h glucose. In addition, paternal history was a stronger determinant in men than in women. An independent positive association with 2-h plasma glucose was found for alcohol use of &amp;gt; 30 g/day in women and for intake of total protein, animal protein, and polyunsaturated fatty acids in men. An independent inverse association with 2-h plasma glucose was demonstrated for height (both sexes), alcohol use of ≤ 30 g/day (both sexes), energy intake (in men), and, unexpectedly, current smoking (in men). CONCLUSIONS The prevalence of diabetes in elderly Caucasians was 8.3%. In men, dietary habits may unfavorably influence glucose tolerance independent of obesity.
Regression of Hypertrophied Rat Pulmonary Arteries in Organ Culture Is Associated With Suppression of Proteolytic Activity, Inhibition of Tenascin-C, and Smooth Muscle Cell Apoptosis
Authors: Kyle Northcote Cowan, Peter Lloyd Jones, Marlene Rabinovitch
Journal: Circulation Research (1999)

Abstract —Increased elastase activity and deposition of the matrix glycoprotein tenascin-C (TN), codistributing with proliferating smooth muscle cells (SMCs), are features of pulmonary vascular disease. In pulmonary artery (PA) SMC cultures, TN is regulated by matrix metalloproteinases (MMPs) and mechanical stress. On attached collagen gels, MMPs upregulate TN, leading to SMC proliferation, whereas on floating collagen, reduced MMPs suppress TN and induce SMC apoptosis. We now investigate the response of SMCs in the whole vessel by comparing attached and floating conditions using either normal PAs derived from juvenile pigs or normal or hypertrophied rat PAs that were embedded in collagen gels for 8 days. Normal porcine PAs in attached collagen gels were characterized by increasing activity of MMP-2 and MMP-9 assessed by zymography and TN deposition detected by Western immunoblotting and densitometric analysis of immunoreactivity. PAs on floating collagen showed reduced activity of both MMPs and deposition of TN. Tenascin-rich foci were associated with proliferating cell nuclear antigen immunoreactivity, and TN-poor areas with apoptosis, by terminal deoxynucleotidyl transferase–mediated nick end labeling assay, but no difference in wall thickness was observed. Although normal rat PAs were similar to piglet vessels, hypertrophied rat PAs showed an amplified response. Increased elastase, MMP-2, TN, and elastin deposition, as well as SMC proliferating cell nuclear antigen positivity, correlated with progressive medial thickening on attached collagen, whereas reduced MMP-2, elastase, TN, and induction of SMC apoptosis accompanied regression of the thickened media on floating collagen. In showing that hypertrophied SMCs in the intact vessel can be made to apoptose and that resorption of extracellular matrix can be achieved by inhibition of elastase and MMPs, our study suggests novel strategies to reverse vascular disease.
The cohesin complex regulates immunoglobulin class switch recombination
Authors: Anne-Sophie Thomas-Claudepierre, Ebe Schiavo, Vincent Heyer, Marjorie Fournier, Adeline Page, Isabelle Robert, Bernardo Reina-San-Martin
Journal: The Journal of Experimental Medicine (2013)

Immunoglobulin (Ig) class switch recombination (CSR) is initiated by the transcription-coupled recruitment of activation-induced cytidine deaminase (AID) to switch regions and by the subsequent generation of double-stranded DNA breaks (DSBs). These DNA breaks are ultimately resolved through the nonhomologous end joining (NHEJ) pathway. We show that during CSR, AID associates with subunits of cohesin, a complex previously implicated in sister chromatid cohesion, DNA repair, and the formation of DNA loops between enhancers and promoters. Furthermore, we implicate the cohesin complex in the mechanism of CSR by showing that cohesin is dynamically recruited to the Sμ-Cμ region of the IgH locus during CSR and that knockdown of cohesin or its regulatory subunits results in impaired CSR and increased usage of microhomology-based end joining.
Outcomes of lung transplantation for bronchiectasis
Authors: Jodie Birch, Katy Hester, Gareth Parry, Kate Gould, John Dark, Stephen Clark, Gerard Meachery, James Lordan, Andrew Fisher, Paul Corris, Anthony De Soyza
Journal: European Respiratory Journal (2012)

Background:  Non-cystic fibrosis bronchiectasis (nCFBr) is an infrequent indication for lung transplantation and poorly described compared to CF and COPD. We describe our experience in the largest series to date.   Methods:  Retrospective review of case-notes and transplant databases from1990 to date (22 years). Two time cohorts were set (1990-2000 and 2001-present date).  Results:  43 patients with nCFBr underwent lung transplantation at our centre. 42 patients had bilateral lung and one had heart-lung transplantation. Median age at transplant was 48 years. Mean pre-transplant FEV1 was 22% predicted (range, 10%-49%; n= 38). At assessment 84% (32 of 38 complete datasets;  32/38 ) were in respiratory failure. Pre-transplant mean BMI was 25.2kg/m 2  and osteoporosis was seen in 50% ( 15/30 ).  Pseudomonas aeruginosa  was isolated in 63% ( 22/35 ) at assessment and in 46% ( 18/39 ) at time of transplant. More patients were transplanted in the first cohort (n=26 vs. n=17). Mean pre-transplant FEV1 (% of predicted) were similar in both time cohorts (21% vs. 23%, p=NS) though patients transplanted in 1990-2000 were younger (mean; 45 vs. 51 years, p=0.026). Our survival values were 74% at 1 year, 64% at 3 years, 61% at 5 years and 48% at 10 years. Infection and multi-organ failure were common causes of death within 1 year post-transplant.   Conclusions:   P. aeruginosa  infection is not universally seen in our cohort. Our survival rates are comparable to prior smaller nCFBr series (Beirne, P.A.  et al.  J Heart Lung Transplant 2005;24:1530-5) but are poorer than those for CF at our centre (Meachery, G.  et al.  Thorax 2008;63:725-731). Patients transplanted for nCFBr have significant osteoporosis rates and are increasingly older at transplantation.
Intimal Smooth Muscle Cells as a Target for Peroxisome Proliferator-Activated Receptor-γ Ligand Therapy
Authors: David Bishop-Bailey, Timothy Hla, Timothy D. Warner
Journal: Circulation Research (2002)

Activation of the nuclear receptor/transcription factor, peroxisome proliferator-activated receptor γ (PPARγ), is a newly defined target for limiting vascular pathologies. PPARγ is expressed in human and animal models of vascular disease, with particularly high levels being present in the cells of the neointimal microenvironment. In the present study, we show that intimal smooth muscle cells in vitro contain higher amounts of functional PPARγ than medial smooth muscle cells. The PPARγ ligand rosiglitazone more potently induced CD36 expression at low concentrations, and cell death by apoptosis at higher concentrations in intimal compared with medial smooth muscle cells. Intimal smooth muscle cells also contained high levels of cyclooxygenase-2 protein, and released a more diverse and larger amount of eicosanoids on arachidonic acid stimulation. Furthermore, when exogenous arachidonic acid was added, PPAR reporter gene activation was induced in a cyclooxygenase inhibitor–sensitive manner, an effect that correlated with an increase in CD36 expression. In summary, intimal smooth muscle cells contain functionally higher levels of PPARγ, PPARγ ligands have high- and low-potency targets in vascular smooth muscle cells, and cyclooxygenase can serve as a source of potential endogenous PPAR ligands. Intimal vascular smooth muscle cells therefore represent a potentially important target for the antiproliferative, and antiatherosclerotic actions of PPARγ ligands.
Predictors of a Medical-Offset Effect Among Patients Receiving Antidepressant Therapy
Authors: D Thompson, T R Hylan, W McMullen, M E Romeis, D Buesching, G Oster
Journal: American Journal of Psychiatry (1998)

Characteristics of patients receiving antidepressant therapy were examined to identify factors that may be associated with a medical-offset effect.In a retrospective study, the authors analyzed claims data from a large health insurer in New England. The study subjects included 1,661 persons initiating treatment for depression with selective serotonin reuptake inhibitors or tricyclic antidepressants between July 1991 and June 1993.Patients with anxiety disorders, coronary heart disease, cancer, and chronic fatigue syndrome and those remaining on their initial regimens of antidepressant therapy for at least 6 months were more likely to experience significant reductions in the costs of medical care services. The number of visits to mental health providers had no effect on the costs of medical services.Specific comorbid conditions and sustained use of antidepressant drugs may be associated with a medical-offset effect for patients receiving treatment for depression.
Disclosing the CXCR4 Expression in Lymphoproliferative Diseases by Targeted Molecular Imaging
Authors: Hans Jürgen Wester, Ulrich Keller, Margret Schottelius, Ambros Beer, Kathrin Philipp-Abbrederis, Frauke Hoffmann, Jakub Šimeček, Carlos Gerngross, Michael Lassmann, Ken Herrmann, Natalia Pellegata, Martina Rudelius, Horst Kessler, Markus Schwaiger
Journal: Theranostics (2015)

Chemokine ligand-receptor interactions play a pivotal role in cell attraction and cellular trafficking, both in normal tissue homeostasis and in disease.In cancer, chemokine receptor-4 (CXCR4) expression is an adverse prognostic factor.Early clinical studies suggest that targeting CXCR4 with suitable high-affinity antagonists might be a novel means for therapy.In addition to the preclinical evaluation of [ 68 Ga]Pentixafor in mice bearing human lymphoma xenografts as an exemplary CXCR4-expressing tumor entity, we report on the first clinical applications of [ 68 Ga]Pentixafor-Positron Emission Tomography as a powerful method for CXCR4 imaging in cancer patients.[ 68 Ga]Pentixafor binds with high affinity and selectivity to human CXCR4 and exhibits a favorable dosimetry.[ 68 Ga]Pentixafor-PET provides images with excellent specificity and contrast.This non-invasive imaging technology for quantitative assessment of CXCR4 expression allows to further elucidate the role of CXCR4/CXCL12 ligand interaction in the pathogenesis and treatment of cancer, cardiovascular diseases and autoimmune and inflammatory disorders.
The Impact of Planned Care and a Diabetes Electronic Management System on Community-Based Diabetes Care
Authors: Victor M. Montori, Sean F. Dinneen, Colum A. Gorman, Bruce R. Zimmerman, Robert A. Rizza, Susan S. Bjornsen, Erin M. Green, Sandra C. Bryant, Steven A. Smith
Journal: Diabetes Care (2002)

OBJECTIVE—The Mayo Health System Diabetes Translation Project sought to assess models of community-based diabetes care and use of a diabetes electronic management system (DEMS). Planned care is a redesigned model of chronic disease care that involves guideline implementation, support of self-management, and use of clinical information systems. RESEARCH DESIGN AND METHODS—We studied adult diabetic patients attending three primary care practice sites in Wisconsin and Minnesota. We implemented planned care at all sites and DEMS in the practice of 16 primary care providers. We assessed quality of diabetes care using standard indicators for 200 patients randomly selected from each site at baseline and at 24 months of implementation. We used multivariable analyses to estimate the association between planned care and DEMS and each quality indicator. RESULTS—Planned care was associated with improvements in measurement of HbA1c (odds ratio 7.0 [95% CI 4.2–11.6]), HDL cholesterol (5.6 [4.1–7.5]), and microalbuminuria (5.3 [3.5–8.0]), as well as the provision of tobacco advice (6.9 [4.7–10.1]), among other performance measures. DEMS use was associated with improvements in all indicators, including microalbuminuria (3.2 [1.9–5.2]), retinal examination (2.4 [1.5–3.9]), foot examinations (2.3 [1.2–4.4]), and self-management support (2.6 [1.7–3.8]). Although planned care was associated with improvements in metabolic control, we observed no additional metabolic benefit when providers used DEMS. CONCLUSIONS—Planned care was associated with improved performance and metabolic outcomes in primary care. DEMS use augmented the impact of planned care on performance outcomes but not on metabolic outcomes. Optimal identification of the best translation of evidence to diabetes practice will require longer follow-up or new care-delivery models.
Computed Tomography Enterography Detects Intestinal Wall Changes and Effects of Treatment in Patients With Crohn's Disease
Authors: David H. Bruining, Edward V. Loftus, Eric C. Ehman, Hassan A. Siddiki, Douglas L. Nguyen, Jeff L. Fidler, James E. Huprich, Jayawant N. Mandrekar, William S. Harmsen, William J. Sandborn, Joel G. Fletcher
Journal: Clinical Gastroenterology and Hepatology (2011)
Predictors of Mortality Over 8 Years in Type 2 Diabetic Patients
Authors: Laura N. McEwen, Andrew J. Karter, Beth E. Waitzfelder, Jesse C. Crosson, David G. Marrero, Carol M. Mangione, William H. Herman
Journal: Diabetes Care (2012)

To examine demographic, socioeconomic, and biological risk factors for all-cause, cardiovascular, and noncardiovascular mortality in patients with type 2 diabetes over 8 years and to construct mortality prediction equations.Beginning in 2000, survey and medical record information was obtained from 8,334 participants in Translating Research Into Action for Diabetes (TRIAD), a multicenter prospective observational study of diabetes care in managed care. The National Death Index was searched annually to obtain data on deaths over an 8-year follow-up period (2000-2007). Predictors examined included age, sex, race, education, income, smoking, age at diagnosis of diabetes, duration and treatment of diabetes, BMI, complications, comorbidities, and medication use.There were 1,616 (19%) deaths over the 8-year period. In the most parsimonious equation, the predictors of all-cause mortality included older age, male sex, white race, lower income, smoking, insulin treatment, nephropathy, history of dyslipidemia, higher LDL cholesterol, angina/myocardial infarction/other coronary disease/coronary angioplasty/bypass, congestive heart failure, aspirin, β-blocker, and diuretic use, and higher Charlson Index.Risk of death can be predicted in people with type 2 diabetes using simple demographic, socioeconomic, and biological risk factors with fair reliability. Such prediction equations are essential for computer simulation models of diabetes progression and may, with further validation, be useful for patient management.