bluuebunny/crossref_metadata_2025_split huggingface dataset:
Current approaches to measuring human islet-antigen specific T cell function in type 1 diabetes
Authors: Mannering S I , Wong F S , Durinovic-Belló I , Brooks-Worrell B , Tree T I , Cilio C M , Schloot N C , Mallone R ,   on behalf of the Immunology of Diabetes Society T-Cell Workshop Committee
Published: September 2010

SummaryType 1 diabetes (T1D) is an autoimmune disease caused by the T cell-mediated destruction of the pancreatic insulin-producing beta cells. Currently there are no widely accepted and standardized assays available to analyse the function of autoreactive T cells involved in T1D. The development of such an assay would greatly aid efforts to understand the pathogenesis of T1D and is also urgently required to guide the development of antigen-based therapies intended to prevent, or cure, T1D. Here we describe some of the assays used currently to detect autoreactive T cells in human blood and review critically their strengths and weaknesses. The challenges and future prospects for the T cell assays are discussed.
Moderate exercise improves leucocyte function and decreases inflammation in diabetes
Authors: Belotto M F , Magdalon J , Rodrigues H G , Vinolo M A R , Curi R , Pithon-Curi T C , Hatanaka E 
Published: September 2010

SummaryThe genesis and progression of diabetes occur due in part to an uncontrolled inflammation profile with insulin resistance, increased serum levels of free fatty acids (FFA), proinflammatory cytokines and leucocyte dysfunction. In this study, an investigation was made of the effect of a 3-week moderate exercise regimen on a treadmill (60% of VO2max, 30 min/day, 6 days a week) on inflammatory markers and leucocyte functions in diabetic rats. The exercise decreased serum levels of tumour necrosis factor (TNF)-α (6%), cytokine-induced neutrophil chemotactic factor 2 alpha/beta (CINC-2α/β) (9%), interleukin (IL)-1β (34%), IL-6 (86%), C-reactive protein (CRP) (41%) and FFA (40%) in diabetic rats when compared with sedentary diabetic animals. Exercise also attenuated the increased responsiveness of leucocytes from diabetics when compared to controls, diminishing the reactive oxygen species (ROS) release by neutrophils (21%) and macrophages (28%). Exercise did not change neutrophil migration and the proportion of neutrophils and macrophages in necrosis (loss of plasma membrane integrity) and apoptosis (DNA fragmentation). Serum activities of creatine kinase (CK) and lactate dehydrogenase (LDH) were not modified in the conditions studied. Therefore, physical training did not alter the integrity of muscle cells. We conclude that moderate physical exercise has marked anti-inflammatory effects on diabetic rats. This may be an efficient strategy to protect diabetics against microorganism infection, insulin resistance and vascular complications.
Local and systemic effects of Na+/K+ATPase inhibition
Authors: Joubert P. H. , Grossmann M. 
Published: September 2010

The positive inotropic and electrophysiological effects of cardiac glycosides on cardiac muscle are mediated through inhibition of Na+/K+ATPase by binding to a specific extracytoplasmic site of the a‐subunit of this enzyme. The inhibition of Na+/K+ATPase affects ionic flux and produces direct local effects on cardiac contractility, electrical excitability and conduction, but also profound systemic effects mainly as a result of haemodynamic changes. These effects are responsible for beneficial therapeutic as well as toxic effects.Inhibition of Na+/K+ATPase results in potentiation of K+loss from cells and Na+entry into cells, so consequently affects action potential generation and propagation. This also underlines the potentiation of certain effects of cardiac glycosides by hypokalemia and hypomagnesaemia, and the effects of changes in calcium homeostasis on the cardiac glycoside pharmacodynamics. Furthermore, inhibition of Na+/Ca++exchange enhances Ca++mobilization and promotes contractility. These effects (locally and systemically) differ greatly, depending on the haemodynamic status and myocardial oxygen supply.Cardiac glycosides have less affinity for Na+/K+ATPases at other sites (e.g. skeletal muscle), but some extracardiac effects (vascular effects, effects on colour vision, CNS and autonomic effects, renal effects) may be related to Na+/K+ATPase inhibition.
Genetic influence in antithrombotic actions of atorvastatin in hypercholesterolaemia
Authors: Puccetti L. , Bruni F. , Pasqui A. L. , Pastorelli M. , Ciani F. , Palazzuoli A. , Acampa M. , Auteri A. 
Published: September 2010

ABSTRACTBackground  Recent data indicate that statins could offer coronary artery disease (CAD) benefit even by mechanisms beyond lipid lowering. Genetic influence has been shown for some antithrombotic actions of statins via oxidized‐low‐density lipoprotein cholesterol (ox‐LDL) receptors and nitric oxide synthase (NOS) activity modulation. The present study was designed to evaluate the influence of ox‐LDL lectin‐like receptor‐1 (LOX‐1) and NOS polymorphisms in the incidence of cardiovascular events in pure hypercholesterolaemic subjects during statin treatment.Materials and methods  A prospective 4‐year study involving 1039 event‐free subjects (643 males, 396 females) treated with atorvastatin (10–40 mg day−1) to reach the appropriate Adult Treatment Panel‐III LDL target of 3·36 mmol L−1. Enrolled subjects were evaluated every 6 months or at a clinical event. LOX‐1 3′UTR/T‐C and NOS G894T polymorphisms were detected by allelic discrimination assays (polymerase chain reaction), lipid profile by enzymatic‐colorimetric method, ox‐LDL by enzyme linked immunosorbent assay, platelet activation by P‐selectin (P‐sel) expression (FACScan), NOS activity (by intracellular citrullin recovery) and homocysteine (high performance liquid chromatography), C‐reactive protein (CRP) by sensitive nephelometric technique.Results  LOX‐1 3′UTR/T showed the strongest association with events in the whole cohort with respect to each other variable including LDL reduction and NOS G894T (OR 4·90, 95% CI 3·19–6·98, P < 0·00001). Smoking influenced events in LDL‐targeted subjects (P < 0·0001). Ox‐LDL and P‐sel were better indicators than LDL or other variables according to 3′UTR/C genotype regardless of the magnitude of LDL reduction (OR 4·21, 95% CI 2·29–6·70 P < 0·0001).Conclusions  LOX‐1 polymorphisms could influence statin effectiveness in CAD prevention by induction of sensitivity to antithrombotic mechanisms such as antiplatelet activity.
Cytogenetic patterns in multiple myeloma after a phase of preceding MGUS
Authors: Kaufmann H. , Ackermann J. , Odelga V. , Sagaster V. , Nösslinger T. , Pfeilstöcker M. , Keck A. , Ludwig H. , Gisslinger H. , Drach J. 
Published: September 2010

ABSTRACTBackground  Presenting the same histological diagnosis, multiple myeloma (MM) shows a large genomic variety, resulting in variable times of overall survival.Materials and methods  To investigate major cytogenetic categories (any 14q‐translocation, t(11;14), t(4;14), 13q‐deletions, 17p‐deletions) and their clinical consequences in MM after a pre‐existing monoclonal gammopathy (MM post‐MGUS), we performed a comparative analysis of 41 patients with MM post‐MGUS and 287 patients with unknown prior history MM (U‐MM).Results  In MM post‐MGUS, a t(11;14) was found to be more frequent than in U‐MM (24% vs. 14%) and it was associated with significantly shortened survival (24 months vs. 70 months in U‐MM; P = 0·01). MM post‐MGUS was further characterized by a higher frequency of 13q‐deletions only (absence of all other specific abnormalities; 28% vs. 12% in U‐MM; P = 0·02). A 13q‐deletion only was an indicator of long survival in MM post‐MGUS (median not yet reached) as opposed to U‐MM (median survival, 29 months; P = 0·001). 17p‐deletions were infrequent in MM post‐MGUS (3% vs. 16% in U‐MM; P = 0·04). Survival times for patients with t(4;14) and/or 17p‐deletions and other abnormalities were similar in both MM patient cohorts.Conclusions  Our data suggest that t(11;14) and 13q‐deletions have distinct prognostic implications in the context of MM post‐MGUS.
Role of raloxifene on platelet metabolism and plasma lipids
Authors: Nanetti L. , Camilletti A. , Francucci C. M. , Vignini A. , Raffaelli F. , Mazzanti L. , Boscaro M. 
Published: September 2010

AbstractBackground  This study was performed to understand the metabolic effects of raloxifene, a selective oestrogen receptor modulator, on platelets in healthy non‐obese postmenopausal women. The data were compared to untreated subjects.Materials and methods  Platelet nitric oxide activity (NO) and peroxynitrite level, platelet inducible and endothelial nitric oxide synthase expression and plasma lipids were evaluated at baseline and after 12 months of raloxifene or placebo treatment.Results  A significant increase of platelet NO and reduction of platelet peroxynitrite levels, as well as a decrease of inducible nitric oxide synthase expression, was observed 12 months after raloxifene therapy as compared to baseline or placebo treatment. Moreover, raloxifene treatment caused a significant increase in high‐density lipoprotein cholesterol and a decrease of total cholesterol and low‐density lipoprotein cholesterol were observed versus baseline values (P < 0·05). A significant positive correlation was observed between high‐density lipoprotein cholesterol and platelet NO (r = 0·76, P < 0·005) in the raloxifene group.Conclusion  Our results showed that raloxifene improves platelet metabolism in healthy postmenopausal women through an increase of the bioavailability of platelet NO by a reduction of iNOS and the beneficial effects on lipid metabolism. This mechanism of action of raloxifene on platelet activity may explain some cardiovascular protective effects of this selective oestrogen receptor modulator.
Impaired aortic elastic properties in patients with systemic sarcoidosis
Authors: Moyssakis I. , Gialafos E. , Tentolouris N. , Floudas C. S. , Papaioannou T. G. , Kostopoulos Ch. , Latsi P. , Vaiopoulos G. , Votteas V. , Rapti A. 
Published: September 2010

AbstractBackground  Systemic sarcoidosis (Sar) is a granulomatous disorder involving multiple organs. Widespread vascular involvement and microangiopathy are common in patients with Sar. In addition, subclinical cardiac involvement is increasingly recognized in patients with Sar. However, data on the effect of Sar on the elastic properties of the arteries and myocardial performance are limited. In this study we looked for differences in aortic distensibility (AoD) which is an index of aortic elasticity, and myocardial performance of the ventricles, between patients with Sar and healthy subjects. In addition, we examined potential associations between AoD and clinical, respiratory and echocardiographic findings in patients with Sar.Materials and methods  A total of 83 consecutive patients (26 male/57 female, mean age 51·1 ± 13·3 years) with Sar, without cardiac symptoms, were included. All patients underwent echocardiographic and respiratory evaluation including lung function tests. Additionally, 83 age‐ and sex‐matched healthy subjects served as controls. AoD was determined non‐invasively by ultrasonography.Results  AoD was lower in the Sar compared to the control group (2·29 ± 0·26 vs. 2·45 ± 0·20 ·10−6 cm2· dyn−1, P < 0·01), while left ventricular mass (LVM) was higher in the Sar group (221·3 ± 50·2 vs. 195·6 ± 31·3 g, P = 0·007). Furthermore, myocardial performance of both ventricles was impaired in the Sar group. Multivariate linear regression analysis in the total sample population demonstrated a significant and independent inverse relationship between AoD and the presence of Sar (P < 0·001). The same analysis in the Sar patients showed that AoD was associated significantly and independently with the stage of Sar, age, systolic blood pressure, LVM and myocardial performance of both ventricles. No significant relationship was found between AoD and disease duration, pulmonary artery pressure or lung function tests.Conclusions  Presence and severity of Sar are associated with reduced aortic distensibility, irrespective of the disease duration, pulmonary artery pressure and lung function. In addition, patients with Sar have increased LVM and impaired myocardial performance.
Angiogenesis in inflammatory bowel disease
Authors: Pousa I. D. , Maté J. , Gisbert J. P. 
Published: September 2010

AbstractBoth ulcerative colitis and Crohn's disease, the two major forms of inflammatory bowel diseases, are recognized, at the moment, as perplexing and challenging clinical entities, in which several molecules and cell types are implicated. Recent molecular evidence proposes the intestinal microvascular remodelling or angiogenesis, as a phenomenon implicated in the pathogenesis of these chronic inflammatory disorders, together with other proposed theories involved in the pathogenesis of inflammatory bowel diseases, such as genetic, microbacterial and immune factors.Intestinal damage is followed by a physiological angiogenesis, but the abnormal expression of pro‐ and anti‐angiogenic molecules and the changes of vascular cell types could reflect a pathological vascular remodelling. Thus, the inflammation may be favoured and maintained by a pathological angiogenesis.A better understanding of the angiogenic process may facilitate the design of more effective therapies for chronic intestinal inflammation.
Expression of the multidrug resistance proteins MRP2 and MRP3 in human cholangiocellular carcinomas
Authors: Rau S. , Autschbach F. , Riedel H. D. , Konig J. , Kulaksiz H. , Stiehl A. , Riemann J. F. , Rost D. 
Published: September 2010

AbstractBackground  Cholangiocellular carcinomas and gallbladder carcinomas are highly aggressive tumours with a poor prognosis and are generally regarded as chemoresistant tumours. Overexpression of ATP‐binding cassette transporters of the multidrug resistance protein (MDR) and multidrug resistance‐related protein (MRP) family in cancer cells is a major cause for the multidrug resistance phenotype in vitro and in vivo. To further define the role of MRP family members in biliary tract cancer, we studied the expression and localization of MRP2 and MRP3 in cholangiocellular carcinomas and gallbladder carcinomas.Materials and methods  The expression and cellular localization of the multidrug resistance proteins MRP2 and MRP3 in human cholangiocellular carcinomas and gallbladder carcinomas were analysed by immunohistochemistry using isoform‐specific antibodies. Expression of MRP isoforms was studied in vitro in Mz‐ChA‐1 cells derived from gallbladder adenocarcinoma by reverse transcription–polymerase chain reaction (RT‐PCR), immunoblotting and immunofluorescence microscopy.Results  Mz‐ChA‐1 cells constitutively expressed MDR P‐glycoproteins, MRP1, MRP2 and MRP3 by RT‐PCR, immunoblotting and immunofluorescence microscopy. MRP2 and MRP3 are expressed in the respective apical and basolateral membrane domains. MRP3 was the predominant MRP isoform in gallbladder carcinomas (93%) and cholangiocellular carcinomas (57%), whereas MRP2 expression was detected in only 29% of gallbladder carcinomas and was undetectable in cholangiocellular carcinomas.Conclusions  Our findings suggest that the intrinsic multidrug resistance of cholangiocellular and gallbladder carcinomas seems to be independent of MRP2 expression while the expression of MRP3 may contribute to the MDR phenotype.
A new coding region polymorphism of human IgLC2
Authors: Naud J.‐F. , Gibson D. M. 
Published: September 2010

AbstractA new allelic form of the human IgLC2 gene is described. The marker involves a T to C substitution in the Cλ2 constant region gene, a silent substitution at amino acid coding position 178 (YAASSYLSL) and two substitutions in the 3′‐flanking region. Analysis of IgLC2 alleles in a total of 60 individuals has indicated a frequency of 0.32 for the new allele, which has been designated IgLC2*B2. The *B1 and *B2 alleles encode T and C, respectively, at nucleotide position 212 in the IgLC2 coding region. Both the *B1 and *B2 alleles are found in individuals homozygous for the single‐copy RFLP allele of IgLC2/IgLC3 (8 kb EcoRI). Knowledge of alleles of this marker will be important for studies on the expression of the IgLC2 and IgLC3 isotypes in normal and autoimmune lymphocyte populations, as the coding regions of the two isotypes differ only at this position. The marker will also be useful in further studies of linkage with other IgLV and IgLC markers and to establish possible correlations with susceptibility to autoimmune disorders.
Spatial and temporal variability of the phenological seasons in Germany from 1951 to 1996
Authors: Menzel Annette , Estrella Nicole , Fabian Peter 
Published: September 2010

AbstractVarious indications for shifts in plant and animal phenology resulting from climate change have been observed in Europe. This analysis of phenological seasons in Germany of more than four decades (1951–96) has several major advantages: (i) a wide and dense geographical coverage of data from the phenological network of the German Weather Service, (ii) the 16 phenophases analysed cover the whole annual cycle and, moreover, give a direct estimate of the length of the growing season for four deciduous tree species. After intensive data quality checks, two different methods – linear trend analyses and comparison of averages of subintervals – were applied in order to determine shifts in phenological seasons in the last 46 years. Results from both methods were similar and reveal a strong seasonal variation. There are clear advances in the key indicators of earliest and early spring (−0.18 to −0.23 d y−1) and notable advances in the succeeding spring phenophases such as leaf unfolding of deciduous trees (−0.16 to −0.08 d y−1). However, phenological changes are less strong during autumn (delayed by + 0.03 to + 0.10 d y−1 on average). In general, the growing season has been lengthened by up to −0.2 d y−1 (mean linear trends) and the mean 1974–96 growing season was up to 5 days longer than in the 1951–73 period. The spatial variability of trends was analysed by statistical means and shown in maps, but these did not reveal any substantial regional differences. Although there is a high spatial variability, trends of phenological phases at single locations are mirrored by subsequent phases, but they are not necessarily identical. Results for changes in the biosphere with such a high resolution with respect to time and space can rarely be obtained by other methods such as analyses of satellite data.
CO2 exchange in an organic field growing barley or grass in eastern Finland
Authors: Maljanen Marja , Martikainen Pertti J. , Walden Jari , Silvola Jouko 
Published: September 2010

AbstractThe CO2 dynamics were measured in an organic soil in eastern Finland during the growing season and wintertime, and the annual CO2 balance was calculated for plots where barley or grass was grown. During the summer, the CO2 dynamics were measured by transparent and opaque chambers using a portable infrared gas analyser for the CO2 analyses. During the winter, the CO2 release was measured by opaque chambers analysing the samples in the laboratory with a gas chromatograph. Statistical response functions for CO2 dynamics were constructed to evaluate the annual CO2 exchange from the climatic data. The net CO2 exchange was calculated for every hour in the snow‐free season. The carbon balance varied extensively depending on the weather conditions, and type and phenology of vegetation. During the growing season, the grassland was a net source while the barley field was a net sink for CO2. However, both soils were net sources for CO2 when autumn, winter and spring were included also. The annual CO2 emissions from the grassland and barley soil were 750 g CO2‐C m−2 and 400 g CO2‐C m−2, respectively. The carbon accumulated in root and shoot biomass during the growing season was 330 g m−2 for grass and 520 g m−2 for barley. The C in the aboveground plant biomass ranged from 43 to 47% of the carbon fixed in photosynthesis (PG) and the proportion of C in the root biomass was 10% of the carbon fixed in photosynthesis. The bare soils had 10–60% higher net CO2 emission than the vegetated soils. These results indicate that the carbon balance of organic soils is affected by the characteristics of the prevailing plant cover. The dry summer of 1997 may have limited the growth of grass in the late summer thus reducing photosynthesis, which could be one reason for the high CO2 release from this grass field.
The impact of diffuse sunlight on canopy light‐use efficiency, gross photosynthetic product and net ecosystem exchange in three forest biomes
Authors: ALTON P. B. , NORTH P. R. , LOS S. O. 
Published: September 2010

AbstractFor three forest canopies (a sparse, boreal needleleaf; a temperate broadleaf; and a dense, tropical, broadleaf stand) light‐use efficiency (LUE) is found to be 6–33% higher when sky radiance is dominated by diffuse rather than direct sunlight. This enhancement is much less than that reported previously for both crops (110%; Choudbury, 2001) and moderately dense temperate woodland (50–180%). We use the land‐surface scheme JULES to interpret the observed canopy response. Once sunflecks and leaf orientation are incorporated explicitly into the scheme, our simulations reproduce convincingly the overall level of canopy gross photosynthetic product (GPP), its enhancement with respect to diffuse sunlight and the mean 15% reduction in productivity observed during the afternoon due to stomatal closure. The LUE enhancement under diffuse sunlight can be explained by sharing of the canopy radiation‐load, which is reduced under direct sky radiance. Once sunflecks are accounted for the advantage of implementing more sophisticated calculations of stomatal conductance (e.g. Ball–Berry and SPA submodels) is less obvious even for afternoon assimilation. Empirical relations are developed between observed carbon flux and the environmental variables total downwelling shortwave radiation (SW), canopy temperature (T) and the fraction of diffuse sky radiance (fDIF). These relations allow us to gauge the impact of increased/reduced insolation on GPP and net ecosystem exchange (NEE). Overall the three stands appear to be fairly stable within global trends and typical interannual variability (SW changing by <15%). Greatest sensitivity is exhibited by the boreal site, Zotino, where NEE falls by 9±4% for a 15% reduction in SW.
Toward a plant‐based proxy for the isotope ratio of atmospheric water vapor
Authors: HELLIKER BRENT R. , GRIFFITHS HOWARD 
Published: September 2010

AbstractAtmospheric water vapor is a major component of the global hydrological cycle, but the isotopic balance of vapor is largely unknown. Here, using models and observations, we show that the leaf water δ18O in the tropical Crassulacean acid metabolism (CAM) epiphyte Tillandsia usneoides is controlled by the δ18O of atmospheric water vapor in a predictable manner, irrespective of precipitation inputs. By taking the leaf‐water‐atmospheric signature as recorded in plant organic material, we have reconstructed the atmospheric water vapor δ18O signature for Miami, FL, USA between 1878 and 2005 using contemporary and herbarium specimens. T. usneoides ranges from Virginia, USA southwards through the tropics to Argentina, and the CAM epiphytic lifeform is widespread in other species. Therefore, there is significant potential for using epiphytes to reconstruct the isotope ratio of atmospheric water (both δ18O and δD) for spatial scales that span over 60° of latitude and temporal scales that cover the last century of global temperature increase.