Intranasal peptide-induced peripheral tolerance: the role of IL-10 in regulatory T cell function within the context of experimental autoimmune encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) is a T cell-mediated autoimmune disease commonly employed as a model for multiple sclerosis. Extensive studies have demonstrated that EAE may be prevented or ameliorated by the intranasal administration of soluble peptides representing encephalitogenic epitopes. There is increasing evidence that this peptide administration may function via the generation of regulatory cells. The mechanism of action of these cells remains controversial and it seems likely that it may vary between experimental models. At present the majority of work on regulatory cells has centred on characterising naturally occurring regulators, or those generated artificially ex vivo, and less is known about induced regulatory cells produced following peptide administration. This report aims to briefly outline the evidence for the existence of natural regulatory T cells and to introduce the sub-types of induced regulatory T cells now recognised.In several of these regulatory cell systems investigated to date, interleukin-10 (IL-10) has been shown to be important in cell function. This has not been directly investigated in a model employing peptide therapy to induce peripheral tolerance, hence the purpose of this study was to investigate the role of IL-10 in the generation of these regulatory cells. This work has employed both a TCR transgenic mouse system, for predominantly in vitro studies of cell function, and an IL-10 knock-out mouse strain to investigate in vivo disease protection. The results summarised in this report demonstrate that IL-10 is fundamentally important in the generation of disease protection following intranasal peptide therapy.     

Risk factors for infection of sow herds with porcine reproductive and respiratory syndrome (PRRS) virus

In 1992, the porcine reproductive and respiratory syndrome virus (PRRSV) of European type (PRRSV-EU) was introduced in Denmark. By 1996, the virus had spread to approximately 25% of the Danish herds. In January 1996, a modified-live vaccine based on the American type of the virus (PRRSV-US) was used in replacement boars for Danish artificial insemination (AI) centres and from July 1996, the vaccine was used in PRRSV-EU infected herds for prevention of disease. Soon after vaccine introduction, PRRSV non-infected herds experienced outbreaks of disease due to infection with PRRSV-US. In this study, we investigated the risk factors (biosecurity level, animals, exposure from PRRSV-US-infected neighbour herds, semen, herd size, pig density and herd density) for infection with PRRSV-US in a cohort of 1071 sow herds; we used a nested case-control study. The retrospective observation period lasted from June 1996 (when they all were non-infected) to October 1997. Seventy-three non-vaccinated, closed sow herds became infected with the vaccine strain during this period. Each case herd was matched with two control herds from the cohort (controls had not been infected at the time of infection in the case herds). The data were analysed using a Cox-regression model. The hazard of infection increased significantly with exposure from PRRSV-US-infected neighbouring herds, purchase of animals from herds incubating PRRSV-US infection, increasing herd size and purchase of semen from boars at PRRSV-US-infected AI centres. The results are consistent with the modified-live vaccine strain spread to other herds by trade with animals and semen and by neighbour (area) transmission. We suggest that virus spread by aerosols was a frequent mode of transmission.     

Einfluss schwach wachsender Apfelunterlagen auf Wachstum,Ertrag und Fruchtgröße verschiedener Sorten – Teil IV: Abschließende Bewertung

From 2001 to 2005 the influence of the dwarfed apple rootstocks M?9 (clone: Burgmer 984), Fleuren 56, Supporter 1, P?16, P?22, J-TE-F, J-TE-E and M?27 on growth, yield and fruit size of the apple varieties ‘Elstar, Elshof’, ‘Boskoop, Herr’ and ‘Jonagored’ was investigated on the locations Auweiler, Dresden-Pillnitz, Osnabrück and Wurzen in Germany.All rootstocks induced a less vegetative growth as the rootstock M?9. In comparison with M?9 the crown volume of the trees ranged from 92% (Supporter 1) to 52% (M?27). The highest yield potential showed the rootstock P?16. Her specific yield (kg/m³) was 17% higher than the specific yield of M?9. All rootstocks produced a lower individual fruit size as M?9. J-TE-E and J-TE-F produced the lowest specific yield.     

Identification of the photochemical decomposition product of chlorothalonil by 13C n.m.r. spectroscopy

The light-induced decomposition of chlorothalonil (2,4,5,6-tetrachloroisophthalonitrile) in benzene and toluene was found to give rise to one and three products respectively. These were shown by gas chromatography-mass spectrometry to be trichlorodicyanobiphenyls and the benzene adduct was fully identified by ¹³C n.m.r. spectroscopy as 2,4-dicyano-3,5,6-trichlorobiphenyl.     

Dormin (Abscisin II), inhibitor of plant DNA synthesis?

Dormin (abscisin II), inhibits growth of Lemna minor cultures. At 1 part per million (3.8x10(-6)M), the culture appears nearly completely dormant but can be revived readily by transferring it to fresh medium free of dormin. The cytokinin benzyladenine, but not auxin or gibberellin, will counteract the dormin effect. Quantitative restoration of normal growth by cytokinin, however, can be achieved only if the dormin concentration does not exceed a critical level. Separation, after phenol-detergent extraction, of nucleic acids on methylated albumin kieselguhr columns showed suppression of nucleic acid synthesis by dormin in all fractions. Inhibition of the synthesis of the DNA fraction seems to precede that of RNA. Cytokinins reverse the process. They promote synthesis of all nucleic acid fractions, but again DNA seems to lead. Further work on the interaction of dormin with growth-promoting hormones might be facilitated by adopting the Monod model of allosteric transition, with, for example, DNA polymerase as the protein, dormin as the inhibitor, and cytokinin or other growth promoters as activators.     

Structure-activity relationships in fungitoxicants related to triforine and chloraniformethan. Part IV: Evaluation of the predictive power of the Hansch analysis by the preparation and testing of further chloraniformethan analogues

Seven chloraniformethan analogues, which were predicted, on the basis of the quantitative Hansch analysis performed previously, to be as active as the parent compound against barley powdery mildew (Erysiphe graminis), were prepared. Their activity as leaf sprays against E. graminis was much lower than that calculated using the regression equations, indicating that the Hansch analysis is not a suitable method for predicting fungitoxicity in this chloraniformethan series of compounds.     

Dietary trials with a commercial chicken hydrolysate diet in 63 pruritic dogs

The owners of 63 pruritic dogs were instructed to feed them a chicken hydrolysate diet exclusively for six weeks as part of diagnostic investigations into non-seasonal pruritus. Ectoparasitism and microbial infections were eliminated during the dietary trial. The dogs' skin lesions, gastrointestinal signs and frequency of defecation were assessed and scores for pruritus were assigned before they started the diet and before and after they resumed their original diet. An adverse food reaction was diagnosed if the pruritus resolved while they were on the diet, but recurred when they resumed their original food regimen. Seventeen of the 63 dogs were withdrawn from the trial, including four which found the diet unpalatable; however, its palatability was reported to be good or excellent in 48 of the dogs. An adverse food reaction alone was diagnosed in nine (19.6 per cent) of the 46 dogs and another nine had an adverse food reaction and atopy. There were gastrointestinal signs in six of the nine dogs with an adverse food reaction, which resolved on the trial diet but recurred when they resumed their original diet.     

Hearth Bread Characteristics: Effect of Protein Quality,Protein Content,Whole Meal Flour,DATEM, Proving Time,and Their Interactions

The effects of protein quality, protein content, ingredients, and baking process of flour blends on hearth loaves were studied. The flour blends varied in protein composition and content. Flours of strong protein quality produced hearth loaves with larger loaf volume, larger bread slice area, and higher form ratio (height/width) than flours of weak protein quality. The effect of protein content on hearth loaf depended on the size distribution of the proteins. Increasing protein content was associated with increased percentage of the largest glutenin polymers, and loaf volume and slice area increased significantly. The form ratio, however, remained unchanged with increasing flour protein content. Strong protein quality flours tolerated addition of whole meal flour better than weak protein quality flours. Increased amount of flour with strong protein quality improved hearth bread characteristics to a larger extent than increased protein content. Diacetyl tartaric acid ester of monoglycerides (DATEM) improved hearth bread characteristics, but the effect was small compared with the effect of protein composition.     

A hereditary disposition for bovine peripheral nerve sheath tumors in Danish Holstein cattle

Background

Peripheral nerve sheath tumors (PNSTs) are frequently found in Danish cattle at slaughter. Bovine PNSTs share several gross and histopathological characteristics with the PNSTs in humans with heritable neurofibromatosis syndromes. The aim of the present study was to investigate a possible hereditary disposition to PNSTs in dairy cattle by statistical analysis performed on data from 567 cattle with PNSTs. Furthermore, a preliminary genome-wide association study (GWAS) was performed on DNA isolated from 28 affected and 28 non-affected Holstein cows to identify loci in the bovine genome involved in the development of PNSTs.

Results

PNSTs were significantly more common in the Danish Holstein breed than in other breeds with 0.49% of Danish Holsteins slaughtered during an eight-year-period having PNSTs. PNSTs also occurred significantly more frequently in the offspring of some specific Holstein sires. Examination of three generation pedigrees showed that these sires were genetically related through a widely used US Holstein sire. The PNSTs included in GWAS were histologically classified as neurofibroma-schwannoma (43%), schwannoma (36%) and neurofibroma (21%) and derived from Holstein cows with multiple PNSTs. A single SNP on chromosome 27 reached genome-wide significance.

Conclusions

Gross and histological characteristics of bovine PNSTs are comparable to PNSTs in humans (schwannomatosis). Danish Holsteins are genetically disposed to develop PNSTs but the examined materials are insufficient to allow determination of the mode of inheritance.