tbuckley/cabot-search huggingface dataset:
Decreased expression of γ-carboxylase in diabetes-associated arterial stiffness: impact on matrix Gla protein
Authors: Marielle Doyon, Patrick Mathieu, Pierre Moreau
Journal: Cardiovascular Research (2012)

Arterial stiffness is accelerated in type 1 diabetic patients. Medial artery calcification (MAC) contributes to the development of arterial stiffness. Vitamin K oxidoreductase (VKOR) reduces the vitamin K required by γ-carboxylase to activate matrix γ-carboxyglutamic acid (Gla) protein (MGP), an inhibitor of vascular calcification. This study aimed to evaluate the hypothesis that diabetes reduces the γ-carboxylation of MGP in the aortic wall, leading to increased vascular calcification, and the role of γ-carboxylase and VKOR in this γ-carboxylation deficit.Type 1 diabetes was induced in male Wistar rats with a single ip injection of streptozotocin. Augmentation of arterial stiffness in diabetic rats was shown by a 44% increase in aortic pulse wave velocity. Aortic and femoral calcification were increased by 26 and 56%, respectively. γ-Carboxylated MGP (cMGP, active) was reduced by 36% and the aortic expression of γ-carboxylase was reduced by 58%. Expression of γ-carboxylase correlated with cMGP (r= 0.59) and aortic calcification (r = -0.57). VKOR aortic expression and activity were not modified by diabetes. Vitamin K plasma concentrations were increased by 191% in diabetic rats. In ex vivo experiments with aortic rings, vitamin K supplementation prevented the glucose-induced decrease in γ-carboxylase expression.Our results suggest that reduced cMGP, through an impaired expression of γ-carboxylase, is involved in the early development of MAC in diabetes, and therefore, in the acceleration of arterial stiffness. A defect in vitamin K uptake by target cells could also be involved.
IgG autoantibody reactivity against bullous pemphigoid (BP) 180 and BP230 in elderly patients with pruritic dermatoses
Authors: C. Feliciani, G. Caldarola, A. Kneisel, E. Podstawa, M. Pfütze, W. Pfützner, M. Hertl
Journal: British Journal of Dermatology (2009)

Background Pruritic dermatoses of the elderly often pose a diagnostic and therapeutic challenge. Specifically, a prodromal phase of bullous pemphigoid (BP) has to be considered in patients with pruritic lesions of polymorphic appearance. These conditions frequently do not fulfil all the clinical, histological and immunopathological criteria for establishing the diagnosis of BP. Objectives To investigate IgG reactivity against the autoantigens of BP, BP180 and BP230, by enzyme-linked immunosorbent assay, in elderly patients affected with various pruritic disorders who had never experienced clinically apparent blisters. Methods The sera of 15 elderly patients with pruritic disorders (group I) were tested for IgG reactivity against BP180 and BP230. Also included were 30 patients with full-blown BP (group II) and 25 age-matched patients with immediate-type allergic reactions (group III). Results Thirty-three per cent of the patients with pruritic disorders (group I) showed IgG against BP230 and/or BP180: four of 15 patients had IgG against BP230 while two of the 15 group I patients were BP180 reactive. All the BP sera (group II) showed IgG reactivity against BP180 and/or BP230. Notably, two of 25 control sera (group III) showed IgG reactivity against either BP180 or BP230. Conclusions The present findings suggest that IgG reactivity against BP230 (i.e. the COOH terminus), and to a lesser extent against BP180, is a common finding in pruritic disorders of the elderly with a wide clinical spectrum. IgG-mediated autoimmunity against the intracellular BP230 may facilitate a chronic, inflammatory response eventually leading to full-blown BP which is presumably associated with IgG against BP180.
A prospective randomized trial comparing the infectious and noninfectious complications of an externalized catheter versus a subcutaneously implanted device in cancer patients.
Authors: B U Mueller, J Skelton, D P Callender, D Marshall, J Gress, D Longo, J Norton, M Rubin, D Venzon, P A Pizzo
Journal: Journal of Clinical Oncology (1992)

PURPOSE To compare the frequency of infectious episodes or other problems occurring with an externalized catheter (Hickman) versus a subcutaneously implanted device (Port-a-Cath, Pharmacia, Piscataway, NJ) in cancer patients, we performed a prospective, randomized study in 100 cancer patients (age range, 5 to 74 years). PATIENTS AND METHODS Patients who were chemotherapy candidates and required an indwelling catheter were monitored prospectively and evaluated during the 180 days after the insertion of the catheter and again at time of study closure. The frequency of catheter use, reason for access, and any problems that might have been related to catheter use were noted. All data were collected prospectively and included the patient's age, sex, underlying malignancy, temperature, and leukocyte and absolute granulocyte counts at the time of catheter insertion and when complications occurred. The time to and reason for removal of the catheter, as well as any intercurrent infectious or mechanical problems, were also determined. RESULTS Most of the infections that occurred were caused by gram-positive organisms, especially staphylococci or streptococci. A total of 22 complications (11 in each group) resulted in removal of the central line. Only one infection in the Hickman catheter group and four in the Port-a-Cath group led to removal of the central line. All other infectious episodes were successfully treated without removal of the catheters. The mean device life was 230 days for the Hickman catheter and 318 days for the Port-a-Cath (not significant). CONCLUSION There were no differences between the two study groups regarding incidence of documented infections or mechanical or thrombotic complications.
Targeted deletion of the inhibitory NF- B p50 subunit in bone marrow-derived cells improves collateral growth after arterial occlusion
Authors: D. de Groot, R. T. Haverslag, G. Pasterkamp, D. P. V. de Kleijn, I. E. Hoefer
Journal: Cardiovascular Research (2010)

Adaptive collateral artery growth (arteriogenesis) is an important mechanism to maintain tissue perfusion upon arterial obstruction. Leucocytes and inflammatory mediators play a crucial role in this process. Depletion of the nuclear factor kappa B (NF-κB) p50 subunit modulates inflammatory processes in cardiovascular disease. We hypothesized that NF-κB p50 is a regulator of the inflammatory response after arterial occlusion and subsequent collateral perfusion. Unilateral femoral artery ligation was performed in NF-κB p50−/− and wild-type (Wt, B6/129PF2) mice. Seven days after arterial occlusion, tissue perfusion restoration was significantly enhanced in NF-κB p50−/− mice compared with Wt mice (42.9 ± 3.9 vs. 32.0 ± 2.6% perfusion recovery, P = 0.04). Transplantation of NF-κB p50−/− bone marrow (bm) into Wt mice and vice versa showed that the effect of p50 subunit depletion can be predominantly attributed to the bone marrow-derived circulating cells (NF-κB p50−/− bm in Wt mice 42.1 ± 1.5%, Wt bm in NF-κB p50−/− mice 35.4±1.5% perfusion recovery). Histological analyses revealed a more elaborate extravasation of monocytes in hindlimb tissue of NF-κB p50−/− mice. Chemotaxis assays confirmed the increased migration ability of NF-κB p50−/− monocytes, which may be due to an observed increased integrin expression. Upon stimulation of blood from NF-κB p50−/− and Wt mice more interleukin-6 was produced, confirming the pro-inflammatory phenotype in absence of the p50 subunit. Depletion of the NF-κB p50 subunit enhances collateral artery growth. Its absence in circulating cells improves tissue perfusion restoration after femoral artery ligation by increasing macrophage influx into the growing collateral vessels.
Trans-Palmitoleic Acid, Metabolic Risk Factors, and New-Onset Diabetes in U.S. Adults
Authors: Dariush Mozaffarian, Haiming Cao, Irena B. King, Rozenn N. Lemaitre, Xiaoling Song, David S. Siscovick, Gökhan S. Hotamisligil
Journal: Annals of Internal Medicine (2010)

The effects of fatty acids on metabolic outcomes are complex and may be influenced by such factors as whether they are endogenously produced or obtained exogenously from specific dietary sources. T...
National income, self-reported wheezing and asthma diagnosis from the World Health Survey
Authors: G. Sembajwe, M. Cifuentes, S. W. Tak, D. Kriebel, R. Gore, L. Punnett
Journal: European Respiratory Journal (2009)

The aims of this study were to quantify and describe the variations in respiratory symptoms and diagnosis prevalence across regions of the world according to national income. In 2002 and 2003, the World Health Organization implemented the World Health Survey (WHS), which used a standardised survey instrument to compile comprehensive baseline information on health and healthcare expenditure. We analysed the WHS data to assess the global patterns of self-reported wheeze and doctor-diagnosed asthma, two commonly reported measures of respiratory health. In total there were 308,218 participants with complete records, from 64 countries. The weighted mean age of the survey population was 43 yrs. Global prevalence of current wheezing symptoms ranged from 2.4% in Vietnam to 24% in Brazil; the prevalence of diagnosed asthma ranged from 1.8% in Vietnam to 32.8% in Australia. Overall, the prevalence of symptoms and diagnosis showed a U-shaped pattern with the largest prevalence reported in low- and high-income countries. The smallest prevalence was consistently found in middle-income countries. These WHS analyses have provided global prevalence estimates of wheeze and doctor-diagnosed asthma using data gathered simultaneously and consistently across six continents. These findings support the need for continued global respiratory illness surveillance for disease prevention, health policy and management.
Bortezomib Induction and Maintenance Treatment in Patients With Newly Diagnosed Multiple Myeloma: Results of the Randomized Phase III HOVON-65/ GMMG-HD4 Trial
Authors: Pieter Sonneveld, Ingo G.H. Schmidt-Wolf, Bronno van der Holt, Laila el Jarari, Uta Bertsch, Hans Salwender, Sonja Zweegman, Edo Vellenga, Annemiek Broyl, Igor W. Blau, Katja C. Weisel, Shulamiet Wittebol, Gerard M.J. Bos, Marian Stevens-Kroef, Christof Scheid, Michael Pfreundschuh, Dirk Hose, Anna Jauch, Helgi van der Velde, Reinier Raymakers, Martijn R. Schaafsma, Marie-Jose Kersten, Marinus van Marwijk-Kooy, Ulrich Duehrsen, Walter Lindemann, Pierre W. Wijermans, Henk M. Lokhorst, Hartmut M. Goldschmidt
Journal: Journal of Clinical Oncology (2012)

We investigated whether bortezomib during induction and maintenance improves survival in newly diagnosed multiple myeloma (MM).In all, 827 eligible patients with newly diagnosed symptomatic MM were randomly assigned to receive induction therapy with vincristine, doxorubicin, and dexamethasone (VAD) or bortezomib, doxorubicin, and dexamethasone (PAD) followed by high-dose melphalan and autologous stem-cell transplantation. Maintenance consisted of thalidomide 50 mg (VAD) once per day or bortezomib 1.3 mg/m(2) (PAD) once every 2 weeks for 2 years. The primary analysis was progression-free survival (PFS) adjusted for International Staging System (ISS) stage.Complete response (CR), including near CR, was superior after PAD induction (15% v 31%; P < .001) and bortezomib maintenance (34% v 49%; P < .001). After a median follow-up of 41 months, PFS was superior in the PAD arm (median of 28 months v 35 months; hazard ratio [HR], 0.75; 95% CI, 0.62 to 0.90; P = .002). In multivariate analysis, overall survival (OS) was better in the PAD arm (HR, 0.77; 95% CI, 0.60 to 1.00; P = .049). In high-risk patients presenting with increased creatinine more than 2 mg/dL, bortezomib significantly improved PFS from a median of 13 months to 30 months (HR, 0.45; 95% CI, 0.26 to 0.78; P = .004) and OS from a median of 21 months to 54 months (HR, 0.33; 95% CI, 0.16 to 0.65; P < .001). A benefit was also observed in patients with deletion 17p13 (median PFS, 12 v 22 months; HR, 0.47; 95% CI, 0.26 to 0.86; P = .01; median OS, 24 months v not reached at 54 months; HR, 0.36; 95% CI, 0.18 to 0.74; P = .003).Bortezomib during induction and maintenance improves CR and achieves superior PFS and OS.
Evaluation of antioxidant systems (coenzyme Q10 and total antioxidant capacity) in morbid obesity before and after biliopancreatic diversion
Authors: Antonio Mancini, Erika Leone, Roberto Festa, Giuseppe Grande, Vincenzo Di Donna, Laura De Marinis, Alfredo Pontecorvi, Roberto Maria Tacchino, Gian Paolo Littarru, Andrea Silvestrini, Elisabetta Meucci
Journal: Metabolism (2008)
Impact of Differences in Fasting Glucose and Glucose Tolerance on the Hyperbolic Relationship Between Insulin Sensitivity and Insulin Responses
Authors: Kristina M. Utzschneider, Ronald L. Prigeon, Darcy B. Carr, Rebecca L. Hull, Jenny Tong, Jane B. Shofer, Barbara M. Retzlaff, Robert H. Knopp, Steven E. Kahn
Journal: Diabetes Care (2006)

OBJECTIVE—To determine whether the hyperbolic relationship between insulin sensitivity and the acute insulin response to glucose (AIRg) exists in subjects with impaired fasting glucose (IFG) or decreased glucose tolerance. RESEARCH DESIGN AND METHODS—We studied 219 healthy subjects (88 male and 131 female subjects, aged 26–75 years) with fasting plasma glucose (FPG) &amp;lt;6.11 mmol/l. Subjects underwent an intravenous glucose tolerance test to determine the insulin sensitivity index (Si), AIRg, and the glucose disappearance constant (Kg), the latter a measure of intravenous glucose tolerance. RESULTS—Si and AIRg were inversely related for the entire cohort, and this relationship was not significantly different from hyperbolic. The inverse relationship between Si and AIRg was not significantly different when compared between groups based on fasting glucose (normal fasting glucose [NFG], FPG &amp;lt;5.56 mmol/l vs. IFG, FPG 5.56–6.11 mmol/l) or by the Kg quartile. However, the curve relating Si and AIRg was left shifted in the IFG compared with NFG group (P &amp;lt; 0.001) and was progressively more left shifted with decreasing Kg (P &amp;lt; 0.001), consistent with decreasing β-cell function. These changes were not observed for the curves relating Si and fasting insulin, suggesting that in the fasting state β-cell function is maintained even in patients with mild IFG. Finally, the disposition index (DI) (Si × AIRg) was calculated as a measure of β-cell function. The DI progressively decreased with increasing FPG, even in the group of subjects classified as NFG. CONCLUSIONS—The inverse relationship between insulin sensitivity and AIRg is consistent with a hyperbola not only in subjects with normal glucose tolerance but also with mild IFG or decreased Kg. Based on a hyperbolic relationship, a decrease in β-cell function can be detected as FPG increases, even in patients who are normal glucose tolerant.
The hepatorenal syndrome
Authors: L DAGHER
Journal: Gut (2001)

Introduction The hepatorenal syndrome (HRS) is defined as the development of renal failure in patients with severe liver disease (acute or chronic) in the absence of any other identifiable cause of renal pathology. It is diagnosed following exclusion of other causes of renal failure in patients with liver disease such as hypovolaemia, drug nephrotoxicity, sepsis, or glomerulonephritis. A similar syndrome may also occur in the setting of acute liver failure. ### DIAGNOSTIC CRITERIA The International Ascites Club (1996) group defined the diagnostic criteria for hepatorenal syndrome1 and these are listed in table 1. View this table: Table 1 Major criteria for a diagnosis of hepatorenal syndrome Two patterns of HRS are observed in clinical practice and these were defined by the International Ascites club.1
Better Glycemic Control and Weight Loss With the Novel Long-Acting Basal Insulin LY2605541 Compared With Insulin Glargine in Type 1 Diabetes
Authors: Julio Rosenstock, Richard M. Bergenstal, Thomas C. Blevins, Linda A. Morrow, Melvin J. Prince, Yongming Qu, Vikram P. Sinha, Daniel C. Howey, Scott J. Jacober
Journal: Diabetes Care (2012)

OBJECTIVE To compare effects of LY2605541 versus insulin glargine on daily mean blood glucose as part of a basal-bolus regimen for type 1 diabetes. RESEARCH DESIGN AND METHODS In this randomized, Phase 2, open-label, 2 × 2 crossover study, 137 patients received once-daily basal insulin (LY2605541 or glargine) plus mealtime insulin for 8 weeks, followed by crossover treatment for 8 weeks. Daily mean blood glucose was obtained from 8-point self-monitored blood glucose profiles. The noninferiority margin was 10.8 mg/dL. RESULTS LY2605541 met noninferiority and superiority criteria compared with insulin glargine in daily mean blood glucose (144.2 vs. 151.7 mg/dL, least squares mean difference = -9.9 mg/dL [90% CI -14.6 to -5.2], P < 0.001). Fasting blood glucose variability and A1C were reduced with LY2605541 compared with insulin glargine (both P < 0.001). Mealtime insulin dose decreased with LY2605541 and increased with insulin glargine. Mean weight decreased 1.2 kg with LY2605541 and increased 0.7 kg with insulin glargine (P < 0.001). The total hypoglycemia rate was higher for LY2605541 (P = 0.04) and the nocturnal hypoglycemia rate was lower (P = 0.01), compared with insulin glargine. Adverse events (including severe hypoglycemia) were similar, although more gastrointestinal-related events occurred with LY2605541 (15% vs. 4%, P < 0.001). Mean changes (all within normal range) were higher for alanine aminotransferase, aspartate aminotransferase, triglycerides, and LDL-cholesterol and lower for HDL-cholesterol with LY2605541 compared with insulin glargine (all P < 0.02). CONCLUSIONS In type 1 diabetes, compared with insulin glargine, LY2605541, a novel, long-acting basal insulin, demonstrated greater improvements in glycemic control, increased total hypoglycemia, and reduced nocturnal hypoglycemia, as well as reduced weight and lowered mealtime insulin doses.
Nicotine, atrial fibrosis, and atrial fibrillation: do microRNAs help to clear the smoke?
Authors: A. Goette
Journal: Cardiovascular Research (2009)

This editorial refers to 'Downregulation of miR-133 and miR-590 contributes to nicotine-induced atrial remodelling in canines' by H. Shan et al., 7 pp.465-472, this issue.2][3][4] These profibrillatory effects appear to depend on the inhibition of ion channels and conduction-slowing properties.One factor known to cause a substantial slowing of electrical impulse propagation in cardiac tissue is an increase in the amount of interstitial collagen.Interstitial fibrosis isolates groups of atrial myocytes as well as individual myocytes. 4,5Thus, the development of interstitial fibrosis affects chamber geometry and mechanical performance of the heart and enhances the likelihood of cardiac arrhythmias such as atrial fibrillation (AF).Recently, it was shown that nicotine abuse accelerates atrial collagen accumulation, leading to symptomatic atrial fibrosis at a younger age. 6Experimentally, a linear correlation between nicotine dose and atrial collagen expression was established.Nevertheless, an exact molecular signalling pathway concerning how nicotine induces atrial fibrosis has not yet been described. 6han et al. used a canine model to analyse the effect of nicotine on atrial structural remodelling. 7Application of nicotine intravenously at a maximal dose of 50 nmol/L kg 21 for 30 days caused the development of interstitial fibrosis.AF inducibility was increased by up to 15-fold.Interestingly, Shan et al. showed that nicotine causes downregulation of certain atrial microRNA species-miR-133 and miR-590which was associated with an upregulation of transforming growth factor (TGF)-b1 (the TGF-b1 gene contains putative binding sites for miR-133) and TGF-b receptor type II (the
Yes, there is (quality of) life after liver transplantation
Authors: S H Uchman, R Cesar
Journal: Hepatology (1996)

Overall, 1-year survival is 79%, 1 and many centers are reporting 1-year survivals approaching 90%.Long- LIVER TRANSPLANTATION!term results, estimated to be 75%, are also quite good.Levy MF, Jennings L, Abouljoud MS, Mulligan DC, However, liver transplantation places a heavy burden Goldstein RM, Husberg BS, Gonwa TA, et al.Quality of on limited health care resources.The average cost per life improvements at
Characterization of a novel trans-sialidase of Trypanosoma brucei procyclic trypomastigotes and identification of procyclin as the main sialic acid acceptor.
Authors: L C Pontes de Carvalho, S Tomlinson, F Vandekerckhove, E J Bienen, A B Clarkson, M S Jiang, G W Hart, V Nussenzweig
Journal: The Journal of Experimental Medicine (1993)

Here we report the presence of a trans-sialidase on the surface of Trypanosoma brucei culture-derived procyclic trypomastigotes. The enzyme is not detected in lysates of bloodstream trypomastigotes enriched for either stumpy or slender forms. The trans-sialidase catalyzes the transfer of alpha(2-3)-linked sialic acid residues to lactose. beta-galactopyranosyl residues are at least 100 times better acceptors for sialic acid than alpha-galactopyranosyl residues. In the absence of efficient acceptors, the purified enzyme transfers sialic acid to water, i.e., it acts as a sialidase. Although the T. cruzi and T. brucei trans-sialidases have very similar donor and acceptor specificities, they are antigenically distinct. Sodium dodecyl sulfate-polyacramide gel electrophoresis under nonreducing conditions and silver staining of the purified trans-sialidase reveals a single band of 63 kD. When the surface membrane of live procyclic trypomastigotes is trans-sialylated, using radioactive sialyllactose as the donor substrate, it appears that the only sialylated surface molecule is procyclin. Pronase treatment of live parasites removes only part of the surface sialic acid, in agreement with recent data showing that the glycosylphosphatidylinositol anchor of procyclin is sialylated (Ferguson, M. A. J., M. Murray, H. Rutherford, and M. J. McConville. 1993. Biochem. J. In press).