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A Millward

Publications and source records attributed to A Millward.

26 records · Page 2Linked to original sources

Engineered secreted T-cell receptor alpha beta heterodimers.

We have produced a soluble form of a mouse alpha beta T-cell antigen receptor (TCR) by shuffling its variable (V) and constant (C) domains to the C region of an immunoglobulin kappa light chain. These chimeric molecules composed of V alpha C alpha C kappa and V beta C beta C kappa chains were efficiently secreted (up to 1 micrograms/ml) by transfected myeloma cells as noncovalent heterodimers of about 95-kDa molecular mass. In the absence of direct binding measurement, we have refined the epitopic analysis of the soluble V alpha C alpha C kappa-V beta C beta C kappa dimers and shown that they react with an anti-clonotypic antibody and two antibodies directed to the C domain of the TCR alpha and beta chains. Conversely, we have raised three distinct monoclonal antibodies against the soluble TCR heterodimers and shown that they recognize surface-expressed TCRs. Two of these antibodies were found to react specifically with the products of the V alpha 2 (V delta 8) and V beta 2 gene segments, respectively. When considered together, these data suggest that these soluble TCR molecules are folded in a conformation indistinguishable from that which they assume at the cell surface.

Amino Acid Sequence↗

Susceptibility to type I diabetes in women is associated with the CD3 epsilon locus on chromosome 11.

Type I diabetes is associated with the DQ loci of the MHC and to a lesser extent with the T cell antigen receptor (TcR) beta chain genes. The non-obese diabetic (NOD) mouse is an animal model of human diabetes, in which up to 90% of female mice develop overt insulin-dependent diabetes. Genetic studies in the NOD mouse suggest that there are at least three diabetogenic genes; one that maps to the MHC, another that may map to the mouse Thy-I locus, and a third that has still to be identified. We have investigated loci in the vicinity of the human Thy-I locus on chromosome 11q23 and report here the results of restriction fragment length polymorphism (RFLP) analysis of the CD3 epsilon locus of 168 Caucasoid patients with type I diabetes. While no association was found between this locus and type I diabetes, a significant difference in the frequency of the CD3 epsilon 8-kb allele was found between male and female patients (0.268 versus 0.430; P less than 0.0025, Pc = 0.02) and between female patients and healthy female controls (0.430 versus 0.267; P less than 0.015). These results suggest that a gene residing on chromosome 11q23 may confer susceptibility to type I diabetes in women.

Adult↗

Complement C4 and heat shock protein 70 (HSP70) genotypes and type I diabetes mellitus.

Type I diabetes is strongly associated with the major histocompatibility complex (MHC) class II region (DR and DQ loci), and to a lesser extent the class III region (complement C4 loci). Restriction fragment length polymorphism analysis was employed to investigate the C4 and heat shock protein 70 (HSP70) loci of 176 patients with type I diabetes and 92 healthy controls. In the patient population there was an excess of deletions of the C4A locus (48.5% vs 22.1%, P less than 0.0005). The HSP70 probe in conjunction with the restriction endonuclease Pst I detects two alleles of 9 or 8.5 kilobases (kb). The 8.5 kb allele was significantly increased in the patient group compared to healthy controls (0.569 vs 0.353, respectively, P less than 0.0005). Furthermore, a C4A deletion nearly always occurred with the 8.5 kb HSP70 allele, suggesting that it may be a marker of the HLA-A1,B8,C4A deletion, DR3 extended haplotype.

Complement C4↗

Characterization of islet cell antibody in insulin dependent diabetes: evidence for IgG1 subclass restriction and polyclonality.

Using an indirect immunofluorescence technique we have investigated the titre, immunoglobulin class, complement-fixing ability, light chain type and IgG subclass of islet cell antibodies (ICA) in the sera of 21 recently diagnosed insulin-dependent diabetics and four non-diabetics before they developed diabetes. In the recently diagnosed patients titres of ICA ranged from 1/10 to 1/640. ICA belonged to the IgG class in all cases and fixed complement in 14 (67%). In all patients tested both kappa and lambda light chains were found, indicating that the antibody is polyclonal. IgG subclasses of ICA were investigated using specific murine monoclonal antibodies. All patients had ICA of the IgG1 subclass and in 16 (76%) this was the only subclass detected. In the remainder, one or more of the other IgG subclasses were found in association with IgG1. In the four pre-diabetic patients ICA fixed complement, was polyclonal and in all cases was of the IgG1 subclass. These characteristics of ICA, therefore, precede the onset of diabetes. The titre of ICA in the pre-diabetics tended to be greater (range 1/320 to (1/1280) than in the recently diagnosed diabetics. These results demonstrate restriction of ICA to the IgG1 subclass.

Adolescent↗

A study of the forces exerted by an oarsman and the effect on boat speed.

A model of the motion of a single-scull rowing hull has been developed and verified against rowing performance data. The model was then used to explore the effect of changes in the cyclic rowing force on the boat speed. The calculations have shown that the shape of the rowing force curve and the proportion of recovery time in the total stroke can have an important effect on the boat speed. It has also been shown that a study of the fluid mechanics of the oar blade would be advantageous in determining whether a reduction in the power wasted can be obtained by changing the ratio of rowing force to normal force.

Engineering↗

Dental erosion in four-year-old children from differing socioeconomic backgrounds.

Although there is very little epidemiological evidence on the prevalence and severity of erosion in children and adults, there have been recent case reports suggesting that the problem of erosion is increasing. This study describes the use of a simple reproducible erosion index. A total of 178 four-year-old children were assessed; almost half of these children showed signs of erosion. The most common site affected was the palatal surface of the upper incisors with 17 percent of the children examined showing visible dentine for greater than one third of the tooth surface. When considering the influence of socioeconomic group on the prevalence of erosion, four out of five children examined in the low socioeconomic group showed low levels of erosion, while a much greater prevalence was observed in the higher socioeconomic groups.

Chi-Square Distribution↗