MAIT cell-MR1 reactivity is highly conserved across multiple divergent species.

Mucosal-associated invariant T (MAIT) cells are a subset of unconventional T cells that recognize small molecule metabolites presented by major histocompatibility complex class I related protein 1 (MR1), via an αβ T cell receptor (TCR). MAIT TCRs feature an essentially invariant TCR α-chain, which is highly conserved between mammals. Similarly, MR1 is the most highly conserved major histocompatibility complex-I-like molecule.

Synthetic 5-amino-6-D-ribitylaminouracil paired with inflammatory stimuli facilitates MAIT cell expansion .

Introduction: Mucosal-associated invariant T (MAIT) cells are a population of innate-like T cells, which mediate host immunity to microbial infection by recognizing metabolite antigens derived from microbial riboflavin synthesis presented by the MHC-I-related protein 1 (MR1). Namely, the potent MAIT cell antigens, 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU) and 5-(2-oxoethylideneamino)-6-D-ribitylaminouracil (5-OE-RU), form via the condensation of the riboflavin precursor 5-amino-6-D-ribitylaminouracil (5-A-RU) with the reactive carbonyl species (RCS) methylglyoxal (MG) and glyoxal (G), respectively. Although MAIT cells are abundant in humans, they are rare in mice, and increasing their abundance using expansion protocols with antigen and adjuvant has been shown to facilitate their study in mouse models of infection and disease.

Absence of markers of betaretrovirus infection in human pulmonary adenocarcinoma.

A proportion of human pulmonary adenocarcinomas has been shown previously to express an antigen related to the Gag protein of a betaretrovirus, Jaagsiekte sheep retrovirus, that causes ovine pulmonary adenocarcinoma. To investigate further the hypothesis that a retrovirus might be present in human lung adenocarcinoma, we examined specimens from patients with lung cancer for evidence of retroviral infection by immunohistochemistry, reverse transcriptase-polymerase chain reaction, immunoblotting and cDNA library screening. Thirty-eight percent of the tumor samples analyzed were positive by immunohistochemistry for Gag-related antigen of Jaagsiekte sheep retrovirus.

Eradication of ovine pulmonary adenocarcinoma by motherless rearing of lambs.

The principles of maedi-visna eradication programmes were applied to a field trial for the eradication of ovine pulmonary adenocarcinoma (OPA). In two maternal flocks the prevalence of gross and histological lesions in slaughtered animals was 18.3 per cent and 29.

PCR examination of bronchoalveolar lavage samples is a useful tool in pre-clinical diagnosis of ovine pulmonary adenocarcinoma (Jaagsiekte).

Ovine pulmonary adenocarcinoma (OPA) is a contagious lung tumour of sheep caused by Jaagsiekte sheep retrovirus (JSRV). The disease is a particular problem in flocks in many parts of the world. The aim of the study was to assess screening methods for individual animals as a prelude to future eradication trials.

Jaagsiekte sheep retrovirus-specific immune responses induced by vaccination: a comparison of immunisation strategies.

Jaagsiekte sheep retrovirus (JSRV) is the aetiological agent of ovine pulmonary adenocarcinoma (OPA). No JSRV-specific immunological responses have been detected in clinical cases of OPA or in experimentally infected lambs. The aim of the present study was to induce immune responses in sheep against JSRV proteins using several immunisation strategies.

Successful induction of ovine pulmonary adenocarcinoma in lambs of different ages and detection of viraemia during the preclinical period.

Ovine pulmonary adenocarcinoma (OPA) can be reproduced consistently in neonatal lambs by intratracheal injection of inocula containing jaagsiekte sheep retrovirus (JSRV). In this study, clinical disease, confirmed pathologically as OPA, was induced in a high proportion of lambs that had been inoculated intratracheally with infectious lung fluid at 1, 3 and 6 months of age. The incubation periods, however, were longer in these three age groups than in 1-week-old lambs that were used as controls.

Systemic immune responses following infection with Jaagsiekte sheep retrovirus and in the terminal stages of ovine pulmonary adenocarcinoma.

Jaagsiekte sheep retrovirus (JSRV) is the aetiological agent of ovine pulmonary adenocarcinoma (OPA). To monitor changes in cellular immune function during JSRV infection, lymphoproliferation in response to various mitogens was measured in the blood of conventionally housed and specific-pathogen-free lambs experimentally infected with JSRV until the development of OPA and compared with uninfected control lambs. In addition, blood samples collected from adult field cases in the terminal stages of OPA and control adult sheep were compared.

Jaagsiekte sheep retrovirus can be detected in the peripheral blood during the pre-clinical period of sheep pulmonary adenomatosis.

Peripheral blood leukocytes (PBLs) and tissue samples from 36 sheep were examined for jaagsiekte sheep retrovirus (JSRV) by hemi-nested PCR. Animals were classified according to the status of sheep pulmonary adenomatosis (SPA), which was confirmed by pathological examination, as follows: (i) sheep with classical SPA (cSPA, n=10), (ii) sheep with atypical SPA (aSPA, n=6), (iii) non-affected sheep from SPA-affected flocks (in-contact, n=10) and (iv) non-affected sheep from SPA-free flocks (control, n=10). JSRV proviral DNA was detected in the PBLs of 10/10 cSPA, 5/6 aSPA, 4/10 in-contact and 0/10 control sheep.

Interactions of Pyrene-Labeled Silica Particles.

Silica spheres were prepared by the Stöber method, and the method of labeling with pyrene, using aminopropylysilane as the linking agent, was optimized. Excimers between particles were formed when high concentrations of label were used. Both surfactant and polyelectrolyte addition were able to cause floc formation when added to suspensions of the silica, but only the surfactant changed the I(1)/I(3) ratio and diminished excimer formation.

Faecal elastase 1: a marker of exocrine pancreatic insufficiency in cystic fibrosis.

Pancreatic elastase 1 (E1), a digestive protease, is synthesized by the acinar cells of the pancreas. Using an enzyme-linked immunosorbent assay, we evaluated stool E1 levels in the following groups of patients. (a) Specimens submitted for occult blood examination from 20 adults, over 3 consecutive days, to assess the inter-day variability in E1 excretion.

Analysis of creatine and creatinine in urine by capillary electrophoresis.

Creatine is found in the urine of subjects ingesting creatine monohydrate as an ergogenic aid. Creatinine, the catabolic breakdown product of creatine, is a major constituent of normal urine. It is of interest to follow the excretion of creatine and creatinine in urine as a function of time after creatine ingestion.

Lack of a specific immune response against a recombinant capsid protein of Jaagsiekte sheep retrovirus in sheep and goats naturally affected by enzootic nasal tumour or sheep pulmonary adenomatosis.

Enzootic nasal tumour (ENT) and sheep pulmonary adenomatosis (SPA) are two contagious adenocarcinomas of the respiratory tract of sheep and goats. Both diseases are associated with related, but distinct, type-D-retroviruses (ENTV and JSRV respectively). No evidence of circulating antibodies has been described in animals affected by either ENT or SPA using antigens from natural sources.

Epithelial tumour cells in the lungs of sheep with pulmonary adenomatosis are major sites of replication for Jaagsiekte retrovirus.

Sheep pulmonary adenomatosis (SPA) is a naturally occurring contagious lung tumour of sheep which has been associated aetiologically with a type D- and B-related retrovirus (Jaagsiekte retrovirus; JSRV). To improve understanding of the aetio-pathogenesis of SPA, the distribution and the sites of JSRV replication in sheep with naturally or experimentally induced SPA or in unaffected controls were identified. New immunological reagents were produced and a blocking enzyme-linked immunosorbent assay (B-ELISA) and an immunohistochemical technique for the detection of JSRV major capsid protein at the tissue and cellular levels were developed.

Experimental transmission of enzootic intranasal tumors of goats.

The successful experimental transmission of enzootic intranasal tumor (EIT) from goat to goat is described. Ten kids, less than 48 hours old, from a flock free of the disease and seronegative for ruminant lentiviruses were inoculated intranasally or intrasinusally with either nasal fluid from goats with naturally occurring EIT or EIT retrovirus concentrated from such fluids. EIT was induced in three kids after 12-24 months.

Enzootic nasal tumour of goats: demonstration of a type D-related retrovirus in nasal fluids and tumours.

Nasal exudate and tumour tissue from goats with enzootic nasal tumours were shown to contain a reverse transcriptase activity associated with a particle of buoyant density typical of retroviruses. The same particle contained a 25,000 Mr protein that cross-reacted with the p27 of Mason-Pfizer monkey virus (MPMV) and with p25 of sheep pulmonary adenomatosis retrovirus. It also contained a low Mr protein related to p10-12 of MPMV.

Pneumonia of lambs following inoculation of isolates of sheep herpesvirus (caprine herpesvirus 1) of different DNA genotypes.

One-day-old, specific pathogen-free lambs, were equally susceptible to infection with three isolates of caprine herpesvirus 1 (CHV1). One of these isolates was genomically different by DNA analysis. Lesions, which were confined to the lung, ranged from a mild interstitial reaction to widespread consolidation.

Association of MHC antigens with susceptibility to and severity of rheumatoid arthritis in multicase families.

A study of HLA association with rheumatoid arthritis (RA) in multicase families has been performed in north east England. Two hundred and nineteen individuals from 13 families were assessed for the presence of RA, and all were HLA typed. Thirty-nine were found to have classical or definite RA by American Rheumatism Association (ARA) criteria.

HLA-DR antigens in primary biliary cirrhosis: lack of association.

A study of HLA-DR antigen in 75 patients with primary biliary cirrhosis has been carried out in order to test the hypothesis that genetic factors related to genes controlling immune responses might be important in the pathogenesis of primary biliary cirrhosis. The frequencies of HLA-DR locus antigens was not significantly different from those in 200 normal controls, nor were those of tissue antigens on the A and B loci. No HLA-DR antigen was significantly associated with the appearance of granulomata on liver biopsy (possibly good prognosis) or with raised serum bilirubin (possibly bad prognosis); nor was there any association between any HLA-DR antigen and adverse reactions to D-penicillamine treatment in 17 patients with such adverse reactions.

Bile reflux and degree of gastritis in patients with gastric ulcer: before and after operation.

The incidence and degree of bile reflux and gastritis has been measured in normal subjects and in patients with gastric ulcer before operation and after treatment by highly selective vagotomy with ulcer excision, Billroth 1 partial gastrectomy, and truncal vagotomy and drainage. Before operation patients had significantly higher (P less than 0.001) bile acid concentrations in the stomach than normal subjects.

HLA antigens and spinal muscular atrophy.

Fifty-four patients with spinal muscular atrophy were examined and HLA typing performed on blood from each. A, B and DR antigens were determined. No statistical difference in antigen prevalence was found between patients and a control population.