bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD26 (dipeptidyl-peptidase IV)-dependent recruitment of T cells in a rat asthma model
Authors: Kruschinski C , Skripuletz T , Bedoui S , Tschernig T , Pabst R , Nassenstein C , Braun A , Von Hörsten S 
Published: December 2004

SummaryCD26 truncates several chemokines as well as neuropeptides and influences immune responses via modulation of cell adhesion and T cell activation, suggesting an involvement of CD26 in asthmatic and airway inflammation. Therefore, Fischer 344 (F344), Brown Norway (BN) and Lewis (LEW) rat strains, which differ in their CD26-like enzymatic activity, were compared using an asthma model. Additionally, two CD26-deficient mutant F344 rat substrains were included and compared to the wild-type F344 substrain. Immunization was performed twice with ovalbumin (OVA), and 2 weeks later the rats were challenged with OVA intratracheally Flow cytometry (FACS) analysis of different leucocyte subsets as well as enzyme-linked immunosorbent assay (ELISA) for IgE levels in the blood and bronchoalveolar lavage (BAL) were performed 24 h after challenge. LEW rats with the lowest CD26 activity among the rat strains investigated here displayed significantly reduced CD4+ T cell numbers in the BAL compared to wild-type F344 and BN rats. Moreover, in asthma, the ratio of CD26+ to CD26– T cell receptor (TCR)-positive cells increased significantly in F344 and LEW but not BN rats. Most intriguingly, in both CD26-deficient F344 rat substrains the number of CD4+ T lymphocytes was markedly reduced compared to wild-type F344. The decrease in T cell recruitment observed in the CD26-deficient rats was associated with significantly reduced OVA-specific IgE-titres. This is the first report to show a remarkably reduced T cell recruitment in rat strains that either lack or exhibit reduced CD26-like enzymatic activity, suggesting a role for CD26 in the pathogenesis of asthma via T cell-dependent processes such as antibody production.
Relevance ofex vivoblood lymphocyte assay forin vivolymphocyte function
Authors: Brattig N W , Timmann C , Abraha R S , Lepping B , Müller-Myhsok B , Horstmann R D 
Published: December 2004

SummaryDeterminations of in vitro proliferative and secretory activities of peripheral blood cells are used widely for research in clinical immunology but, to our knowledge, have not been evaluated as to their power to reflect in vivo activities quantitatively. Here, we addressed this question by quantitatively correlating the in vitro secretion of interleukin (IL)-5 by peripheral blood cells to the in vivo activity of IL-5 as reflected by peripheral-blood eosinophil counts. Studying 458 humans exposed to transmission of the nematode Onchocerca volvulus, IL-5 was measured in the supernatants of 0·02-ml whole-blood cells cultured in the presence of O. volvulus extract or mitogen. O. volvulus-reactive IL-5 secretion was correlated significantly to blood eosinophilia in a quantitative manner explaining 15·1% (95% CI 8·3–19·9%) of the variability of eosinophil counts. Interestingly, correlations were obtained only if parasite counts were included in the calculation using multiple regression analysis. The results show that in vitro assays of minute amounts of blood lymphocytes may quantitatively reflect activities of the entire lymphocyte population in vivo.
Role of p38 MAPK and NF-kB for chemokine release in coculture of human eosinophils and bronchial epithelial cells
Authors: Wong C K , Wang C B , Ip W K , Tian Y P , Lam C W K 
Published: December 2004

SummaryEosinophils are principal effector cells of inflammation in allergic asthma, characterized by their accumulation and infiltration at inflammatory sites mediated by the chemokine eotaxin and their interaction with adhesion molecules expressed on bronchial epithelial cells. We investigated the modulation of nuclear factor-κB (NF-κB) and the mitogen-activated protein kinase (MAPK) pathway on the in vitro release of chemokines including regulated upon activation normal T cell expressed and secreted (RANTES), monokine induced by interferon-γ (MIG), monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-8, and interferon-inducible protein-10 (IP-10) upon the interaction of human bronchial epithelial BEAS-2B cells and eosinophils. Gene expression of chemokines was evaluated by RT-PCR and the induction amount of chemokines quantified by cytometric bead array. NF-κB and p38 MAPK activities were assessed by electrophoretic mobility shift assay and Western blot, respectively. The interaction of eosinophils and BEAS-2B cells was found to up-regulate the gene expression of the chemokines IL-8, MCP-1, MIG, RANTES and IP-10 expression in BEAS-2B cells, and to significantly elevate the release of the aforementioned chemokines except RANTES in a coculture of BEAS-2B cells and eosinophils. IκB-α phosphorylation inhibitor, BAY 11–7082, and p38 MAPK inhibitor, SB 203580 could decrease the release of IL-8, IP-10 and MCP-1 in the coculture. Together, the above results show that the induction of the release of chemokines in a coculture of epithelial cells and eosinophils are regulated by p38 MAPK and NF-κB activities of BEAS-2B cells, at least partly, through intercellular contact. Our findings therefore shed light on the future development of more effective agents for allergic and inflammatory diseases.
Real‐time PCR assay for quantification of Tilletia caries contamination of UK wheat seed
Authors: McNeil M. , Roberts A.M.I. , Cockerell V. , Mulholland V. 
Published: December 2004

A quantitative real‐time PCR assay using TaqMan chemistry has been developed to quantify the level of Tilletia spp. contamination in wheat‐seed lots. In the UK wheat seed is predominantly contaminated with Tilletia caries (syn. Tilletia tritici), and the probability of detecting other Tilletia spp. is negligible. DNA standards, prepared from T. caries spores, were calibrated using a set of 26 seed samples, with T. caries contamination levels ranging from 0 to 1000 spores per seed. The linear calibration model obtained by the regression of log10 (number of spores per seed + 1) on mean log10 DNA (µg) produced a coefficient of determination (R2) of 0·904. The calibration model was tested using 226 seed samples; of these, 91% fell within the 95% confidence intervals. Of the 21 samples that were outside the limits, 16 were overpredictions and five underpredictions. The five underpredictions were all from seed samples where contamination was less than one spore per seed. The model predicts that samples with 44 pg of DNA will be below one spore per seed with 95% probability. Of the 226 test samples compared with this threshold, 99 contained less than 44 pg DNA, and these were found to have less than one spore per seed by microscopic assay. This real‐time assay allows an increase in test throughput and provides the sensitivity required for an advisory threshold of one spore per seed.
Expression of carbohydrate xenoantigens on porcine peripheral nerve
Authors: Magnusson Stefan , Strokan Valeri , Svensson Lola , Månsson Jan‐Eric , Rydberg Lennart , Breimer Michael E. 
Published: December 2004

Abstract:  Background:
The use of thin easily revascularized cutaneuos nerve autografts, which has been the gold standard, or the alternative use of nerve allografts or artificial grafts for nerve reconstructing have all their pros and cons. Nerve xenotransplantation may offer a potential alternative. In a potential pig to human nerve xenograft transplantation set‐up several porcine antigen barriers have to be considered such as carbohydrate antigens system like the blood group A/O, the Galα1‐3Gal (αGal) and the Hanganutziu‐Deicher (HD) antigens. The swine leukocyte protein antigens system may also have to bee considered. The knowledge of the antigen expression on pig peripheral nerves is today limited.The present study describes the distribution of glycolipid based carbohydrate xenoantigens in ischiadicus nerve from blood group A and O pigs.Methods:  Glycolipid fractions were separated on thin layer chromatography plates and immunostained with human AB sera, biotinylated Griffonia simplicifolia isolectin B4, monoclonal antibodies reacting with the HD antigen and with blood group A antigens based on different core saccharide structures. In addition, the subcellular distribution of αGal and HD antigens were studied by light‐ and electron‐microscopical immunohistochemistry. The total amount of neutral glycolipids was 15 mg/g tissue for both blood group A and O nerves with mono‐glycosylceramides as the dominating component.Results and conclusions:  The total amount of acidic glycolipids (gangliosides and sulpholipids) was 9 mg/g tissue for both the blood group O and A nerves with sulphatides as the dominating components. Analyses of the glycolipid fractions showed strong expression of both the αGal and the HD antigens in nerves from both blood group A and O pigs. In addition, small amounts of blood group A antigens were expressed in nerves from blood group A pigs. Staining of neutral glycolipids from blood group A pigs using monoclonal antibodies reacting with A antigen having different core structures suggested that the A epitope expressed on pig ischiadicus nerves is based on the type 1 core chain structure. Light and electron microscopical studies on the αGal and HD‐antigen distribution revealed that the neural cells were αGal antigen negative. Endothelial cells of blood vessels, and lymphatic and perineural cells expressed αGal antigen. Both endothelial cells and myelinized axons revealed positively labelled for the HD antigen.
Early weaning of piglets fails to exclude porcine lymphotropic herpesvirus
Authors: Mueller Nicolas J. , Kuwaki Kenji , Knosalla Christoph , Dor Frank J. M. F. , Gollackner Bernd , Wilkinson Robert A. , Arn Scott , Sachs David H. , Cooper David K. C. , Fishman Jay A. 
Published: December 2004

Abstract:  Background:  Xenotransplantation using pigs as source species carries a risk for the activation of latent herpesviruses from the porcine donor and potential transmission to the recipient. In pig‐to‐baboon xenotransplantation, activation of porcine cytomegalovirus (PCMV) has been associated with xenograft injury and an increased incidence of consumptive coagulopathy and graft loss. Activation of porcine lymphotropic herpesvirus (PLHV)‐1 was not observed in pig‐to‐baboon solid organ xenotransplantation, but was associated with a syndrome of post‐transplantation lymphoproliferative disorder (PTLD) after allogeneic stem cell transplantation in pigs.Material and Methods:  Early weaning of piglets was used to try to reduce the viral burden of xenograft donors. This consisted of separating the piglets of a litter from the sow within the first 2 weeks after birth and raising them in isolation from the remaining herd.Results:  We have previously demonstrated that PCMV could be excluded from source animals by early weaning of piglets. However, early weaning failed to exclude PLHV‐1 from source pigs.Conclusions:  This disparity between PCMV and PLHV‐1 reflects differing pathogenesis of infection of these herpesviruses. New approaches will be needed to exclude PLHV‐1 from pig colonies.
Importance of evacuatory disturbance in evaluation of faecal incontinence after third degree obstetric tear
Authors: Shatari T. , Hayes J. , Pretlove S. , Toosz‐Hobson P. , Radley S. , Keighley M. R. B. 
Published: December 2004

AbstractObjective  To correlate anorectal function including rectal evacuation with anorectal physiology and endoanal ultrasound in women with third degree obstetric anal sphincter injury repaired at the time of delivery.Patients and methods  Forty‐four women with repaired third degree tears underwent anorectal physiology, anal ultrasonography and clinical assessment using the St. Marks incontinence score (0–24). Evacuatory disturbance was assessed by questionnaire.Results  There was a significant correlation between disturbed evacuation and incontinence symptoms (P =0.030). There was also a significant correlation between disturbed evacuation and internal anal sphincter (IAS) injury (P = 0.026), but there was no correlation with external anal sphincter (EAS) injury. There was a correlation between disturbed evacuation and low resting anal pressure (P = 0.013). Although IAS defects were associated with low anal pressure, only the correlation with Maximum Squeeze Pressure reached statistical significance (P = 0.018).Conclusion  Women with evacuatory disturbance after repaired third degree tears have a greater level of incontinence than those whose emptying is normal. This association is related to internal sphincter injury and reduced anal sphincter pressures.
Hospital volume and outcome of rectal cancer surgery in Denmark 1994–99
Authors: Harling H. , Bülow S. , Møller L. N. , Jørgensen T. ,   the Danish Colorectal Cancer Group
Published: December 2004

AbstractObjective  The association between hospital volumen and outcome of major cancer surgery is being debated at present. We analysed the outcome of rectal cancer surgery in Denmark during the period 1994–99.Methods  All patients with a first‐time rectal cancer were registered in a national database during the 5‐year period. In this observational cohort study, the influence of hospital case volume on resectional procedure, complications, 30‐day mortality and 5‐year mortality was analysed.Results  The register comprised 5021 patients. Surgery was performed in 27 hospitals with < 15 operations per year, 15 hospitals with 15–30 operations per year and 11 hospitals with > 30 operations per year. In a multivariate model, the risk of permanent colostomy was significantly increased in the group of low‐volume hospitals. On the contrary, volume did not influence the risk of anastomotic leakage, 30‐day mortality and 5‐year mortality. However, a large variation in 5‐year mortality was observed particularly within the low‐volume group of hospitals.Conclusions  In this study, only risk of having a permanent colostomy during surgery for rectal cancer was significantly related to hospital case volume. When individual hospitals were analysed, a large variation in 5‐year mortality was observed within the low‐volume group of hospitals.
Usefulness of total cholesterol/HDL‐cholesterol ratio in the management of diabetic dyslipidaemia
Authors: Gimeno‐Orna J. A. , Faure‐Nogueras E. , Sancho‐Serrano M. A. 
Published: December 2004

AbstractAims  Our aim was to evaluate the usefulness of the total cholesterol/HDL‐cholesterol ratio (TC/HDL) in predicting the cardiovascular risk of Type 2 diabetic patients.Methods  Prospective cohort study with inclusion of 418 Type 2 diabetic individuals with follow‐up until the appearance of a cardiovascular event. The predictive power of updated mean lipid values during follow‐up was analysed by means of Cox proportional hazard models. An estimate was made of the relative risk (RR) conferred by high levels of TC/HDL stratified by LDL‐cholesterol levels.Results  Sixty‐six cardiovascular events occurred during an average follow‐up of 4.7 years (sd 1.5). The main lipid predictor of vascular events was mean TC/HDL ratio [hazard ratio (HR) = 1.46; 95% confidence interval (CI) 1.25, 1.7; P < 0.0001]. In the multivariate model with simultaneous inclusion of mean TC/HDL and mean LDL‐cholesterol, both were significant predictors of cardiovascular disease [HR (1 unit) = 1.37; 95% CI 1.16, 1.62; P = 0.0003 and HR (1 mmol/l) = 1.5; 95% CI 1.04, 2.18; P = 0.03, respectively]. The LDL adjusted RR for cardiovascular events due to high TC/HDL ratio, with 4.5 cut‐off point, was 2.5 (95% CI 1.4, 4.3; P = 0.0007). For the stratum of subjects with average LDL cholesterol < 3.5 mmol/l, RR was 1.2 (95% CI 0.5, 2.8; P = NS) and for the stratum of average LDL cholesterol > 3.5 mmol/l, RR was 4 (95% CI 1.8, 9; P = 0.00013), with heterogeneity among strata (P = 0.044).Conclusions  It could be useful to include the TC/HDL ratio in treatment guides for diabetic dyslipidaemia, given their high predictive value and strong interaction with LDL cholesterol.
Insulino‐mimetic and anti‐diabetic effects of vanadium compounds
Authors: Srivastava A. K. , Mehdi M. Z. 
Published: December 2004

AbstractCompounds of the trace element vanadium exert various insulin‐like effects in in vitro and in vivo systems. These include their ability to improve glucose homeostasis and insulin resistance in animal models of Type 1 and Type 2 diabetes mellitus. In addition to animal studies, several reports have documented improvements in liver and muscle insulin sensitivity in a limited number of patients with Type 2 diabetes. These effects are, however, not as dramatic as those observed in animal experiments, probably because lower doses of vanadium were used and the duration of therapy was short in human studies as compared with animal work. The ability of these compounds to stimulate glucose uptake, glycogen and lipid synthesis in muscle, adipose and hepatic tissues and to inhibit gluconeogenesis, and the activities of the gluconeogenic enzymes: phosphoenol pyruvate carboxykinase and glucose‐6‐phosphatase in the liver and kidney as well as lipolysis in fat cells contributes as potential mechanisms to their anti‐diabetic insulin‐like effects. At the cellular level, vanadium activates several key elements of the insulin signal transduction pathway, such as the tyrosine phosphorylation of insulin receptor substrate‐1, and extracellular signal‐regulated kinase 1 and 2, phosphatidylinositol 3‐kinase and protein kinase B activation. These pathways are believed to mediate the metabolic actions of insulin. Because protein tyrosine phosphatases (PTPases) are considered to be negative regulators of the insulin‐signalling pathway, it is suggested that vanadium can enhance insulin signalling and action by virtue of its capacity to inhibit PTPase activity and increase tyrosine phosphorylation of substrate proteins. There are some concerns about the potential toxicity of available inorganic vanadium salts at higher doses and during long‐term therapy. Therefore, new organo‐vanadium compounds with higher potency and less toxicity need to be evaluated for their efficacy as potential treatment of human diabetes.
The TGF‐β1 gene codon 10 polymorphism contributes to the genetic predisposition to nephropathy in Type 1 diabetes
Authors: Patel A. , Scott W. R. , Lympany P. A. , Rippin J. D. , Gill G. V. ,   the Warren 3/UK GoKind Study Group, Barnett A. H. , Bain S. C. 
Published: December 2004

AbstractAims  We hypothesize that transforming growth factor‐beta (TGF‐β), a multifunctional growth factor which plays a key role in the development of tissue fibrosis, may be involved in the pathophysiology of diabetic nephropathy. Our aim was to examine three polymorphisms within the TGF‐β1 gene, in codons 10, 25 and 263, for association with nephropathy in Type 1 diabetes.Methods  We conducted a large case–control study using cases with Type 1 diabetes and clinical nephropathy. Controls were Type 1 diabetic subjects who have been injecting insulin for at least 50 years and have extremely low risk of nephropathy. Genotyping was by polymerase chain reaction with sequence‐specific primers.Results  There was a significant difference in the frequency of the TGF‐β1 codon 10 genotypes in the diabetic nephropathy group (n = 420) when compared with the controls (n = 410, P = 0.007). There were no significant differences when the frequencies of the TGF‐β1 codons 25 and 263 genotypes in the diabetic nephropathy group were compared with the control group.Conclusions  In our study the TGF‐β1 codon 10 polymorphism is associated with nephropathy in Type 1 diabetes and variation in this gene may contribute to the genetic predisposition to this complication in Type 1 diabetes.
Early onset severe pre‐eclampsia: expectant management at a secondary hospital in close association with a tertiary institution
Authors: Oettle Charl , Hall David , Roux Adele , Grové Debbie 
Published: December 2004

Objectives  Early onset severe pre‐eclampsia is ideally managed in a tertiary setting. We investigated the possibility of safe management at secondary level, in close co‐operation with the tertiary centre.Design  Prospective case series over 39 months.Setting  Secondary referral centre.Population  All women (n= 131) between 24 and 34 weeks of gestation with severe pre‐eclampsia, where both mother and fetus were otherwise stable.Methods  After admission, frequent intensive but non‐invasive monitoring of mother and fetus was performed. Women were delivered on achieving 34 weeks, or if fetal distress or major maternal complications developed. Transfer to the tertiary centre was individualised.Main outcome measures  Prolongation of gestation, maternal complications, perinatal outcome and number of tertiary referrals.Results  Most women [n= 116 (88.5%)] were managed entirely at the secondary hospital. Major maternal complications occurred in 44 (33.6%) cases with placental abruption (22.9%) the most common. One maternal death occurred and two women required intensive care admission. A mean of 11.6 days was gained before delivery with the mean delivery gestation being 31.8 weeks. The most frequent reason for delivery was fetal distress (55.2%). There were four intrauterine deaths. The perinatal mortality rate (≥1000 g) was 44.4/1000, and the early neonatal mortality rate (≥500 g) was 30.5/1000.Conclusions  The maternal and perinatal outcomes are comparable to those achieved by other tertiary units. This model of expectant management of early onset, severe pre‐eclampsia is encouraging but requires close co‐operation between secondary and tertiary institutions. Referrals to the tertiary centre were optimised, reducing their workload and costs, and patients were managed closer to their communities.
Effects of long term administration of KUR‐1246, a selective β2‐adrenoceptor agonist, on pregnant sheep and their fetuses
Authors: Murata Satoshi , Matsuda Tadashi , Kiguchi Sumiyoshi , Kobayashi Mamoru , Cho Kazutoshi , Okuyama Kazuhiko 
Published: December 2004

Objective  To evaluate the safety of KUR‐1246 as a tocolytic agent, we examined the effects of its long term infusion on respiratory and cardiovascular systems and general metabolism in pregnant sheep and their fetuses.Design  Animal experiment with chronically instrumented ewes and their fetuses.Setting  Center for animal experiments, Hokkaido University School of Medicine, Japan.Sample  Eight Suffolk ewes at 117 to 120 days of gestation.Methods  At 120–124 days of gestation, ewes (n= 4) were infused intravenously for 24 hours with KUR‐1246 at 0.03 μg/kg/minute, a dose that completely inhibits oxytocin‐induced uterine contractions in pregnant sheep. The controls received saline instead (n= 4). Statistical comparisons were carried out by repeated‐measures ANOVA followed by Dunnett's test.Main outcome measures  Maternal and fetal values of heart rate, blood pressure, plasma electrolytes, glucose, insulin and non‐esterified fatty acid levels, and blood gases and lactate level.Results  The maternal plasma levels of KUR‐1246 increased and reached a plateau at 15 hours or later from the start of the infusion, whereas the fetal levels of it were below the lower limit of quantification (0.1 ng/mL) throughout the experiment. Significant differences over time between the ewes that had received with KUR‐1246 and the controls were found for the following parameters: maternal heart rate, blood lactate, plasma glucose, and plasma insulin levels, and fetal plasma glucose and plasma insulin levels (P < 0.05). In the KUR‐1246 treated ewes, significant changes from the pre‐infusion value were detected in maternal blood lactate and fetal plasma glucose levels within 6 hours from the start of the infusion (P < 0.05). No significant differences were observed in other parameters in either ewes or fetuses.Conclusion  The physiologic changes induced by a 24‐hour infusion of KUR‐1246 were transient and considered to be within the compensatory capacity in both pregnant ewes and their fetuses, suggesting that KUR‐1246 is a potentially safe tocolytic agent for use by long term infusion.