bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevention of myocardial fibrosis by N-acetyl-seryl-aspartyl-lysyl-proline in diabetic rats
Authors: Castoldi Giovanna , Di Gioia Cira R. T. , Bombardi Camila , Perego Carla , Perego Lucia , Mancini Massimiliano , Leopizzi Martina , Corradi Barbara , Perlini Stefano , Zerbini Gianpaolo , Stella Andrea 
Published: June 2009

Ac-SDKP (N-acetyl-seryl-aspartyl-lysyl-proline) is a physiological tetrapeptide hydrolysed by ACE (angiotensin-converting enzyme). In experimental models of hypertension, Ac-SDKP has antifibrotic effects in the heart; however, the role of Ac-SDKP in diabetic cardiomyopathy is currently unknown. The aim of the present study was to evaluate the effect of Ac-SDKP on cardiac systolic and diastolic function, and interstitial and perivascular fibrosis in the heart of diabetic rats. Diabetes was induced in 55 Sprague–Dawley rats by streptozotocin injection. Control rats (n=18) underwent only buffer injection. Out of the 55 diabetic rats, 19 were chronically treated with insulin and 13 with the ACEI (ACE inhibitor) ramipril (3 mg·kg−1 of body weight·day−1). At 2 months after the onset of diabetes, Ac-SDKP (1 mg·kg−1 of body weight·day−1) was administered by osmotic minipumps for 8 weeks to eight control rats, 13 diabetic rats, seven diabetic rats treated with ramipril and nine insulin-treated diabetic rats. Diabetic rats had a significant increase in blood glucose levels. Left ventricular interstitial and perivascular fibrosis, and TGF-β1 (transforming growth factor-β1) protein levels were increased in diabetic rats, but not in insulin-treated diabetic rats and ramipril-treated diabetic rats, compared with control rats. Ac-SDKP administration significantly reduced left ventricular interstitial and perivascular fibrosis in diabetic rats and in diabetic rats treated with ramipril. This was accompanied by a significant reduction in active TGF-β1 and phospho-Smad2/3 protein levels in myocardial tissue of diabetic rats. Echocardiography showed that diabetes was associated with increased end-systolic diameters, and depressed global systolic function and diastolic dysfunction, as assessed by transmitral Doppler velocity profile. These changes were completely reversed by insulin or ramipril treatment. Ac-SDKP treatment partially restored diastolic function in diabetic rats. In conclusion, Ac-SDKP administration in diabetic rats reduces left ventricular interstitial and perivascular fibrosis, active TGF-β1 and phospho-Smad2/3 levels, and improves diastolic function. Taken together, these findings suggest that, by inhibiting the TGF-β/Smad pathway, Ac-SDKP protects against the development of diabetic cardiomyopathy.
Will Routine Annual Influenza Prevention and Control Systems Serve the United States Well in a Pandemic?
Authors: Ringel Jeanne S. , Moore Melinda , Zambrano John , Lurie Nicole 
Published: June 2009

ABSTRACTObjective: To assess the extent to which the systems in place for prevention and control of routine annual influenza could provide the information and experience needed to manage a pandemic.Methods: The authors conducted a qualitative assessment based on key informant interviews and the review of relevant documents.Results: Although there are a number of systems in place that would likely serve the United States well in a pandemic, much of the information and experience needed to manage a pandemic optimally is not available.Conclusions: Systems in place for routine annual influenza prevention and control are necessary but not sufficient for managing a pandemic, nor are they used to their full potential for pandemic preparedness. Pandemic preparedness can be strengthened by building more explicitly upon routine influenza activities and the public health system’s response to the unique challenges that arise each influenza season (eg, vaccine supply issues, higher than normal rates of influenza-related deaths). (Disaster Med Public Health Preparedness. 2009;3(Suppl 2):S160–S165)
Mesenchymal cells inhibit expansion but not cytotoxicity exerted by gamma–delta T cells
Authors: Petrini I. , Pacini S. , Petrini M. , Fazzi R. , Trombi L. , Galimberti S. 
Published: June 2009

AbstractBackground  Multipotent mesenchymal stromal cells (MSCs) exert a relevant immunosuppressive activity by inhibiting T‐ and B‐lymphocytes, natural killer (NK) cells and dendritic cell expansion. Nevertheless, a possible activity on gamma/delta T cells has still not been evaluated.Gamma–delta T lymphocytes play an important role in the control of cancer and they have been shown to be implicated in graft‐vs.‐host disease. Thus, modulation of activation and proliferation of these cells could be relevant for therapeutic purposes.Materials and methods  Peripheral blood mononuclear cells from 21 healthy donors were used as source for gamma–delta T cells, expanded in presence of 10 IU mL−1 interleukin‐2 (IL‐2) and 1 μM zoledronate. MSCs were recovered from patients undergoing routine total hip replacement surgery, and characterised by flow cytometry. Cytotoxicity on multiple myeloma and melanoma cell lines was assessed by measuring dilution of the carboxyfluorescein diacetate succinimydylester dye (CFSE). Gamma–delta T cells were then incubated with MSCs in contact cultures, and with addition of MSC‐conditioned medium.Results  In this article we confirmed that (1) in vitro expanded gamma–delta T cells play a significant anti‐proliferative effect on multiple myeloma and melanoma cells and (2) multipotent mesenchymal stromal cells effectively suppress the ex vivo expansion of T cells carrying a specific T‐cell receptor gene (TCR) rearrangement, Vgamma9/Vdelta2, induced by the combination of IL‐2 and zoledronate, without interfering with their cytotoxic activity.Discussion  These findings contribute to explain the activity of ex vivo expanded mesenchymal cells, suggesting that MSCs would interact with gamma–delta T lymphocytes.Conclusion  This effect could be relevant in separating graft‐vs.‐host from the graft‐vs.‐tumour effect, especially considering the possibility of modulating T‐lymphocytes activity by the immunomodulating drugs now available.
Renal artery stenosis predicts adverse cardiovascular and renal outcome in patients with peripheral artery disease
Authors: Amighi J. , Schlager O. , Haumer M. , Dick P. , Mlekusch W. , Loewe C. , Böhmig G. , Koppensteiner R. , Minar E. , Schillinger M. 
Published: June 2009

AbstractBackground  Patients with symptomatic peripheral artery disease (PAD) are considered cardiovascular high‐risk patients. Our aim was to investigate whether incidental renal artery stenosis (RAS) increases the risk for adverse cardiovascular and renal outcomes in these patients.Materials and methods  We prospectively enrolled 487 consecutive patients admitted for revascularization of symptomatic PAD and performed a renal overview angiogram categorizing RAS as absent (0–29%), moderate (30–59%) and severe (≥ 60%) respectively. Clinical follow‐up was for median 15 months (IQR 12–22) for the occurrence of major adverse events [MAE: composite of death, myocardial infarction (MI), stroke, percutaneous coronary intervention, coronary bypass surgery, amputation and kidney failure]. Glomerular filtration rates (GFR) were obtained at 12 months to quantify the course of renal function.Results  A severe RAS was found in 76 patients (15·6%). Overall MAE occurred in 121 patients (24·8%), the composite endpoint of MI, stroke, amputation and death occurred in 101 patients (20·7%). Patients with a severe RAS had a 1·87‐fold increased adjusted risk for MAE (95% CI 1·12–3·12, P = 0·017), a 2·51‐fold increased adjusted risk for occurrence of the composite endpoint of MI, stroke, amputation and death (95% CI 1·45–4·34, P = 0·001) and a 2·93‐fold increased risk for death (95% CI 1·41–6·08, P = 0·004), compared to those of patients without RAS respectively. We observed a significant association between the decrease of GFR over the 12‐month follow‐up period and the severity of RAS by multivariable analysis (P = 0·044).Conclusion  Severe RAS in patients with symptomatic PAD is an independent predictor of major adverse cardiovascular events, adverse renal outcome and mortality.
Effects of AT1‐ and β‐adrenergic receptor antagonists on TGF‐β1‐induced fibrosis in transgenic mice
Authors: Seeland U. , Schäffer A. , Selejan S. , Hohl M. , Reil J.‐C. , Müller P. , Rosenkranz S. , Böhm M. 
Published: June 2009

AbstractBackground Transforming growth factor‐β1 (TGF‐β1) is involved in interstitial remodelling promoting collagen synthesis and suppressing collagen degradation by inhibition of collagenases. TGF‐β1 mediates angiotensin II‐dependent effects and modulates β1‐adrenergic signalling. To study the effect of neuroendocrine antagonism on TGF‐β‐induced hypertrophic and fibrotic phenotype, we treated TGF‐β1 (Cys223,225Ser) transgenic mice (TGF‐β1‐TG) with either the β1‐receptor blocker metoprolol (MET), the angiotensin II type I (AT1)‐receptor antagonist telmisartan (TEL) or an antibody blocking TGF‐β1 signalling (TGFβ1‐sR‐Ab).Material and Methods Transforming growth factor‐β1‐TG mice (8 weeks) overexpressing TGF‐β1 were treated with either TEL (10 mg kg−1), MET (350 mg kg−1) or a soluble TGF‐β1 receptor antibody (1 mg kg−1) for 6 weeks. Morphological analyses of interstitium and cardiomyocytes were related to expression of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) by immunoblotting and zymography.Results In TGF‐β1‐TG mice, myocardial interstitial total collagen content was fourfold elevated compared to that of controls (P < 0·05) and was lowered under the treatment with TEL (P < 0·05). Protein expression of TIMP‐1 and ‐4 was increased in TGF‐β1‐TG but inhibited by TEL (TIMP‐1 and TIMP‐4) and MET (TIMP‐1), while collagenase activity was decreased in TGF‐β1‐TG and normalized by treatment with TEL (MMP‐1 and MMP‐13) and MET (MMP‐1) (P < 0·05). Morphometric measurements of cardiomyocyte diameter and area demonstrated similar antihypertrophic effects for all treatment groups.Conclusion The AT1‐antagonist TEL reduced myocardial hypertrophy and interstitial fibrosis in TGF‐β1‐TG mice by normalizing MMP/TIMP ratio. β1‐Adrenergic inhibition by MET as well as TGF‐β1 antagonism induced antihypertrophic rather than antifibrotic effects. Inhibition of both renin‐angiotensin system and β1‐adrenergic system may exert different but synergistic effects to reduce myocardial remodelling.
Elevated tryptase levels selectively cluster in myeloid neoplasms: a novel diagnostic approach and screen marker in clinical haematology
Authors: Sperr W. R. , El‐Samahi A. , Kundi M. , Girschikofsky M. , Winkler S. , Lutz D. , Endler G. , Rumpold H. , Agis H. , Sillaber C. , Jäger U. , Valent P. 
Published: June 2009

AbstractBackground Recent data suggest that tryptase, a mast cell enzyme, is expressed in neoplastic cells in myeloid leukaemias. In several of these patients, increased serum tryptase levels are detectable.Materials and methods We have determined serum tryptase levels in 914 patients with haematological malignancies, including myeloproliferative disorders (n = 156), myelodysplastic syndromes (MDS,n = 241), acute myeloid leukaemia (AML,n = 317), systemic mastocytosis (SM,n = 81), non‐Hodgkin′s lymphoma (n = 59) and acute lymphoblastic leukaemia (n = 26). Moreover, tryptase was measured in 136 patients with non‐neoplastic haematological disorders, 102 with non‐haematological disorders and 164 healthy subjects.Results In healthy subjects, the median serum tryptase was 5·2 ng mL−1. Elevated serum tryptase levels were found to cluster in myeloid neoplasm, whereas almost all patients with lymphoid neoplasms exhibited normal tryptase. Among myeloid neoplasms, elevated tryptase levels (> 15 ng mL−1) were recorded in > 90% of patients with SM, 38% with AML, 34% with CML and 25% with MDS. The highest tryptase levels, often > 1000 ng mL−1, were found in advanced SM and core‐binding‐factor leukaemias. In most patients with non‐neoplastic haematological disorders and non‐haematological disorders analysed in our study, tryptase levels were normal, the exception being a few patients with end‐stage kidney disease and helminth infections, in whom a slightly elevated tryptase was found.Conclusions In summary, tryptase is a new diagnostic marker of myeloid neoplasms and a useful test in clinical haematology.
Enhanced terrestrial carbon uptake in the Northern High Latitudes in the 21st century from the Coupled Carbon Cycle Climate Model Intercomparison Project model projections
Authors: QIAN HAIFENG , JOSEPH RENU , ZENG NING 
Published: June 2009

AbstractThe ongoing and projected warming in the northern high latitudes (NHL; poleward of 60 °N) may lead to dramatic changes in the terrestrial carbon cycle. On the one hand, warming and increasing atmospheric CO2 concentration stimulate vegetation productivity, taking up CO2. On the other hand, warming accelerates the decomposition of soil organic matter (SOM), releasing carbon into the atmosphere. Here, the NHL terrestrial carbon storage is investigated based on 10 models from the Coupled Carbon Cycle Climate Model Intercomparison Project. Our analysis suggests that the NHL will be a carbon sink of 0.3 ± 0.3 Pg C yr−1 by 2100. The cumulative land organic carbon storage is modeled to increase by 38 ± 20 Pg C over 1901 levels, of which 17 ± 8 Pg C comes from vegetation (43%) and 21 ± 16 Pg C from the soil (8%). Both CO2 fertilization and warming enhance vegetation growth in the NHL. Although the intense warming there enhances SOM decomposition, soil organic carbon (SOC) storage continues to increase in the 21st century. This is because higher vegetation productivity leads to more turnover (litterfall) into the soil, a process that has received relatively little attention. However, the projected growth rate of SOC begins to level off after 2060 when SOM decomposition accelerates at high temperature and then catches up with the increasing input from vegetation turnover. Such competing mechanisms may lead to a switch of the NHL SOC pool from a sink to a source after 2100 under more intense warming, but large uncertainty exists due to our incomplete understanding of processes such as the strength of the CO2 fertilization effect, permafrost, and the role of soil moisture. Unlike the CO2 fertilization effect that enhances vegetation productivity across the world, global warming increases the productivity at high latitudes but tends to reduce it in the tropics and mid‐latitudes. These effects are further enhanced as a result of positive carbon cycle–climate feedbacks due to additional CO2 and warming.
Effects of variations in simulated changes in soil carbon contents and dynamics on future climate projections
Authors: YUROVA ALLA YU , VOLODIN EUGENY M. , ÅGREN GÖRAN I. , CHERTOV OLEG G. , KOMAROV ALEXANDER S. 
Published: June 2009

AbstractClimatic variables have major effects on all components and processes of the global carbon (C) cycle, including soil C contents and dynamics, which in turn have significant feedback effects on the global climate. We have investigated the interactive effects between soil C and projected climatic changes using the Institute of Numerical Mathematics Climate Model (INMCM) climate–C cycle model coupled to three soil organic matter dynamics models [the Lund–Potsdam–Jena (LPJ) soil biogeochemistry, ROMUL and Q models] based on three markedly differing conceptual interpretations of soil organic matter transformation (biochemical, discrete succession and continuous quality, respectively). According to simulations using all these couplings the positive effect of CO2 fertilization on plant productivity outweighed the negative effects of increased soil temperature on soil C, consequently soils were projected to contain 10–104 Pg more C in 2100 than in the preindustrial period. However, the projected soil respiration rates tended to be higher and additional C storage lower when the LPJ soil biochemistry model was used rather than either the ROMUL or Q models. Global temperatures for 2100 predicted by the INMCM coupled to either the ROMUL or Q models were almost identical, but 0.4 °C lower than those predicted by the INMCM coupled to the LPJ soil biochemistry model. The differences in global predictions obtained with the ROMUL and Q models were smaller than expected given the fundamental difference in their formulations of the relationship between the quality and temperature sensitivity of soil organic matter decomposition.
Consensus guidelines into the management of epilepsy in adults with an intellectual disability
Authors: Kerr M. , Scheepers M. , Arvio M. , Beavis J. , Brandt C. , Brown S. , Huber B. , Iivanainen M. , Louisse A. C. , Martin P. , Marson A. G. , Prasher V. , Singh B. K. , Veendrick M. , Wallace R. A. 
Published: June 2009

AbstractBackground  Epilepsy has a pervasive impact on the lives of people with intellectual disability and their carers. The delivery of high‐quality care is impacted on by the complexity and diversity of epilepsy in this population. This article presents the results of a consensus clinical guideline process.Results  A Delphi process identified a list of priority areas for the development of evidence‐based guidelines. All guidelines were graded and consensus on scoring was achieved across the guideline group.Conclusion  There is a dearth of high‐quality evidence from well‐constructed studies on which to base guidance. However, the development of internationally derived consensus guidelines may further support the management of epilepsy in adults with an intellectual disability.
Enhancing capacity to make sexuality‐related decisions in people with an intellectual disability
Authors: Dukes E. , McGuire B. E. 
Published: June 2009

AbstractAim  The aim of the study was to apply an intervention to the area of sexual knowledge in order to determine if capacity to make sexuality‐related decisions could be improved.Method  The study adopted a single subject design using multiple baseline method with four adults with a moderate intellectual disability. The intervention consisted of individually tailored sex education adapted from Living Your Life (Bustard 2003). Treatment was offered to each participant twice weekly for a 10‐week period on a one‐to‐one basis. The Sexual Consent and Education Assessment (SCEA, Kennedy 1993) was used for measurement purposes. The SCEA K‐Scale (knowledge) and the S‐Scale (safety practices) were administered weekly throughout the baseline, treatment and post‐treatment phases of the study. Staff concerns were also assessed using the SCEA Inappropriate Sexual Behaviour Scale.Results  All four participants improved their decision‐making capacity in all targeted areas as measured by improvements in K‐Scale and S‐Scale scores. Staff concerns were not increased as indicated by results on the Inappropriate Sexual Behaviour Scale. Six‐month follow‐up data for three of the participants showed maintenance of scores on the S‐Scale and some decay in scores on the K‐Scale from post‐intervention performance.Conclusion  The results demonstrate that tailored sexuality education can improve capacity to make sexuality‐related decisions.
Association of single nucleotide polymorphisms in secreted frizzled‐related protein 1 gene with bone mineral density in Japanese women
Authors: Ohnaka Keizo , Yamamoto Ken , Nakamura Kenjiro , Adachi Masahiro , Kawate Hisaya , Kono Suminori , Takayanagi Ryoichi 
Published: June 2009

Aim:  Recent studies have demonstrated that the Wnt signaling pathway plays an important role in bone metabolism. The purpose of this study was to examine whether the gene of secreted frizzled‐related protein 1 (SFRP1), a Wnt antagonist, is involved in the etiology of osteoporosis using association study.Methods:  Seven single nucleotide polymorphisms (SNP) in the SFRP1 gene were genotyped and analyzed for association with bone mineral density (BMD) in 931 Japanese women (63.5 ± 6.7 years old, mean ± standard deviation).Results:  One SNP (rs16890444) located in intron and another (rs3242) located in the 3′‐untranslated region of the sFRP1 gene were significantly associated with the lumbar spine BMD value, and BMD values for both the femoral neck and the total hip, respectively. Women with the T/T genotype of the former SNP had a lower BMD value of the lumbar spine (L2–L4) compared with those with C/C or C/T (BMD value adjusted for age, duration after menopause, and body mass index: 0.781 vs 0.830, P = 0.037), while women with the T/T genotype of the latter SNP had higher BMD values of femoral neck and total hip compared with those with C/C or C/T (adjusted BMD value: femoral neck, 0.721 vs 0.633, P = 0.025; total hip, 0.834 vs 0.737, P = 0.027).Conclusion:  These results suggest that the SFRP1 may be a candidate gene for a BMD determinant, but further studies need to consolidate the present findings.
Relationship between female mating strategy, litter success and offspring dispersal
Authors: Laloi David , Richard Murielle , Fédérici Pierre , Clobert Jean , Teillac‐Deschamps Pauline , Massot Manuel 
Published: June 2009

AbstractThe relationship between mating systems and dispersal has generally been studied at the population and species levels. It has hardly ever been investigated at the individual level, by studying the variations of mating and dispersal strategies between individuals. We investigated this relationship in a natural population of the common lizard (Lacerta vivipara). Assuming that dispersal has a genetic basis, juvenile dispersal would be expected to be more family‐dependent in monoandrous litters than in polyandrous litters. The opposite pattern was observed. Thus, maternal effects and/or litter effects play a greater role than genetic determinism in shaping the dispersal phenotype of juveniles. Moreover, the relationship between female mating strategy and offspring dispersal depended on litter success, in a way consistent with an influence of mother‐offspring competition. Such a link between mating and dispersal strategies of individuals may have major repercussions for the way we consider the roles of these processes in population functioning.
Radiotherapy for patients with localized hormone‐refractory prostate cancer: results of the Patterns of Care Study in Japan
Authors: Sasaki Tomonari , Nakamura Katsumasa , Ogawa Kazuhiko , Onishi Hiroshi , Okamoto Atsushi , Koizumi Masahiko , Shioyama Yoshiyuki , Mitsumori Michihide , Teshima Teruki ,   the Japanese Patterns of Care Study Working Subgroup on Prostate Cancer
Published: June 2009

OBJECTIVETo evaluate the clinical results of radiotherapy (RT) for patients with regionally localized hormone‐refractory prostate carcinoma (HRPC).PATIENTS AND METHODSAs part of a Patterns of Care Study in Japan, a nationwide survey was conducted of RT for patients with prostate adenocarcinoma. We reviewed the detailed information of 140 patients with regionally localized HRPC who received RT between 1996 and 1998, and between 1999 and 2001, in 117 randomly selected institutes in Japan. The median (range) age of the patients was 74 (51–94) years, and their tumours were defined as well (14), moderately (51) or poorly (54) differentiated, or of unknown differentiation (21). The median (range) interval between hormonal therapy (HT) and RT was 32.5  (1.1–168.4) months. Ninety‐five patients had T3‐4 tumours and 28 had regional lymph node metastases before treatment. The median (range) prostate‐specific antigen levels before the initial HT and before RT were 35.0 (1.5–276) and 10.0 (0.06–760.3) ng/mL, respectively. External beam RT was administered, with a median total dose of 66 Gy; 70 patients (50%) received pelvic irradiation.RESULTSAt a median follow‐up of 20.7 months, the 5‐year overall and clinical progression‐free survival rates (95% confidence interval) were 48.1 (36–60)% and 36.7 (26–47)%, respectively. Although there were distant metastases in 46 patients, only six had local progression. There was late morbidity of grade ≥3 in six patients.CONCLUSIONTo the best of our knowledge, this study comprises the largest series of regionally localized HRPC treated with RT reported to date. RT might have a limited role for HRPC, because in most patients RT failed, with distant metastasis.