PubMed Health⌕ Search

Biomedical subjects

S W Reid

Publications and source records attributed to S W Reid.

At least 55 records · Page 3Linked to original sources
PubMed1998

Recognition surfaces of MHC class I.

Recent crystallographic results have provided close to atomic resolution views of the recognition events mediated by MHC class I molecules. The specificity-conferring interaction of MHC class I/peptide with a T-cell antigen receptor (TCR) appears dependent on certain key interactions with the MHC scaffold. These interactions, in particular those of the TCR V alpha domain, define a standard orientation for TCR binding. Previous studies on biologically significant variations in the TCR recognition surface presented by a series of MHC/variant peptide complexes can be reassessed in the light of this TCR-binding mode. The interaction of CD8 with MHC class I resembles that between antibody and antigen in the use of loops from the CD8 structure. The interaction is of very low affinity and buries equivalent surface area to that between the TCR and MHC class I but while the TCR/MHC interface shows poor surface shape complementarity the match in the conservative interaction between MHC and CD8 is precise.

Animals↗
PubMed1998

Flat, hurdle and steeple racing: risk factors for musculoskeletal injury.

A retrospective case-control study was conducted to identify and quantify risk factors for serious musculoskeletal injury sustained at 4 Australian metropolitan racetracks. During the period of study (August 1988-July 1995) there were 196 cases from flat racing, 52 cases from hurdle racing and 53 cases from steeplechases. The incidences of fatal musculoskeletal injuries per start for flat, hurdle and steeple races were 0.06, 0.63 and 1.43% respectively. Logistic regression identified harder track surfaces, horses being older than age 3 years, one racecourse (Flemington) and jumping races as significant risk factors which increased the risk of musculoskeletal breakdown. The incidence of fatal musculoskeletal injuries for flat races at the 4 study tracks was similar to that reported in the UK but less than the USA. Death rates for hurdle and steeple races in the study population were higher than in the UK. Strategies to reduce the incidence of serious musculoskeletal injuries may include avoidance of excessively hard track surfaces through closer regulation of track moisture content; implementation of more rigorous prerace lameness examinations of horses, particularly older horses; and altering the design and number of jumps in hurdle and steeple races. The quantification of risk, as we have reported here, is the first step towards addressing the causes of musculoskeletal breakdown and should help in applying a reasoned approach to intervention measures that may be effective in reducing racing injuries.

Analysis of Variance↗
PubMed1998

The bHLH-Zip transcription factor Tfeb is essential for placental vascularization.

Tfeb is a member of the basic Helix-Loop-Helix-Zipper family of transcription factors. In vitro studies have shown that TFEB can bind DNA as a homodimer or as a heterodimer with three closely related family members: MITF, TFE3 and TFEC. While mutations of Mitf have been shown to affect the development of a number of cell types including melanocytes, osteoclasts, and masts cells, little is known about the phenotypic consequences of mutations at Tfe3, Tfeb and Tfec. Here we show that mice with a targeted disruption of Tfeb die between 9.5 and 10.5 days in embryonic development and have severe defects in placental vascularization. Tfeb is expressed at low levels in the embryo but at high levels in the labyrinthine trophoblast cells of the placenta. While labyrinthine cells are present in the mutant Tfeb placenta, they fail to express VEGF, a potent mitogen required for normal vasculogenesis of the embryo and extraembryonic tissues. In Tfeb mutant embryos the embryonic vasculature forms normally but few vessels are seen entering the placenta and those that do enter fail to thrive and branch normally. Our results indicate that Tfeb plays a critical role in the signal transduction processes required for normal vascularization of the placenta.

Animals↗
PubMed1997

HLA class I binding motifs derived from random peptide libraries differ at the COOH terminus from those of eluted peptides.

Recombinant HLA-A2, HLA-B8, or HLA-B53 heavy chain produced in Escherichia coli was combined with recombinant beta2-microglobulin (beta2m) and a pool of randomly synthesised nonamer peptides. This mixture was allowed to refold to form stable major histocompatability complex (MHC) class I complexes, which were then purified by gel filtration chromatography. The peptides bound to the MHC class I molecules were subsequently eluted and sequenced as a pool. Peptide binding motifs for these three MHC class I molecules were derived and compared with previously described motifs derived from analysis of naturally processed peptides eluted from the surface of cells. This comparison indicated that the peptides bound by the recombinant MHC class I molecules showed a similar motif to naturally processed and presented peptides, with the exception of the peptide COOH terminus. Whereas the motifs derived from naturally processed peptides eluted from HLA-A2 and HLA-B8 indicated a strong preference for hydrophobic amino acids at the COOH terminus, this preference was not observed in our studies. We propose that this difference reflects the effects of processing or transport on the peptide repertoire available for binding to MHC class I molecules in vivo.

Amino Acid Sequence↗
PubMed1997

Combined structural and immunological refinement of HIV-1 HLA-B8-restricted cytotoxic T lymphocyte epitopes.

This study demonstrates that use of structural information improves the definition and optimization of cytotoxic T lymphocyte (CTL) epitopes. Epitope optimization usually requires numerous truncated peptides or a reverse immunogenetic approach, where the peptide binding motif is used to predict epitopes. These binding motifs do not reliably predict all peptides which are CTL epitopes. Comparison of 24 peptides eluted from HLA-B8 with 10 HLA-B8-restricted defined CTL epitopes demonstrated that known epitopes varied considerably at anchor positions. We used structural information based on determination of the crystal structure of the HLA-B8-GGKKKYKL complex to reassess previously described CTL epitopes, to predict new epitopes, and to predict the consequences of naturally occurring variation within epitopes. These predictions were confirmed by cytotoxicity and binding assays. Use of combined structural and immunological data more accurately defines the true peptide-binding motif of a restriction element than eluted peptide data allows.

Antigenic Variation↗
PubMed1997

Risk factors associated with musculoskeletal injuries in Australian thoroughbred racehorses.

Risk factors for musculoskeletal injury in racing Thoroughbreds were investigated in a case-control study conducted at racetracks administered by the Australian Jockey Club. Univariable analysis of 137 cases from the official Veterinary Surgeon's reports and an equal number of randomly selected controls from the Australian Race Results identified field size, barrier position and class of race as being significantly associated with breakdown (P < 0.05). Multiple logistic regression was then used to investigate the effect of each putative risk factor whilst controlling for all others. Horses at greater risk were older, started from a wider barrier position, ran at the same distance as their previous race and raced in the highest class of race. There was no significant difference between tracks or significant association with track condition. The incidence of fatalities in the study population was less than that reported in the UK and USA.

Animals↗
PubMed1997

The use of enzyme linked immunosorbent assays to investigate the prevalence of Trypanosoma equiperdum in Ethiopian horses.

A field study involving 309 horses was undertaken in the provinces of Arsi and Bale in the Ethiopian highlands to investigate the prevalence of Trypanosoma equiperdum infections using enzyme linked immunosorbent assays (ELISAs) for the detection of both trypanosomal antigen and antibody. Adult horses of both sexes were examined for clinical signs of T. equiperdum infection and serum samples were collected for the assays. One hundred and one horses showed the presence of trypanosomal antibodies in their serum and 70 animals showed typical clinical signs of dourine. Nineteen horses showed the presence of trypanosomal antigen. Eight horses were positive for both T. equiperdum antibody and antigen. Blood and genital washes from seven antigenaemic horses were inoculated into mice and rabbits in an attempt to isolate trypanosomes but none became infected. Statistical analysis of the results of antibody assays indicated that there were significant differences in the distribution of serologically positive horses in the different clinical groupings, with seropositivity increasing with the severity of the observed clinical signs (P < 0.001). There was also a positive correlation between the presence of circulating trypanosomal antigen and clinical evidence of infection. Although it was not possible to obtain direct parasitological evidence of infection, the results of the serological assays, together with the clinical signs of disease observed in many of the horses, provide strong circumstantial evidence that T. equiperdum occurs in Arsi and Bale provinces of Ethiopia. Furthermore, in view of the large number of horses in Ethiopia and the unrestricted movement of animals throughout the country it is likely that dourine may be more widespread in Ethiopia than is currently realised. The assays used show potential for diagnosis of dourine, but to be widely applied in field situations for the diagnosis and control of dourine in Africa they require validation of their specificity and sensitivity.

Animals↗
PubMed1997

The genetic basis of resistance to Ostertagia circumcincta in lambs.

The relationship between Ostertagia (Teladorsagia) circumcincta and sheep is one of the best understood host-parasite relationships in any species. The key components of resistance have been quantified, the extent of genetic control has been established for lambs, and methods now exist to breed lambs which will be both more resistant to worms and more productive than unselected lambs. A major gene for resistance has been identified within or around the major histocompatibility complex, and this gene appears to be the strongest yet identified for resistance to any parasite species. The most important mechanisms of resistance are local IgA responses which regulate worm fecundity and immediate hypersensitivity responses which regulate worm burdens. IgA responses develop before effective immediate hypersensitivity responses. Good simulation models now exist to predict, for example, outbreaks of disease and the response of sheep to selection. The challenge now is to use our improved understanding of the population biology to develop even better simulation models and to produce expert systems based on these models which can be used by veterinarians and others to determine optimal procedures for individual farms to control disease and reduce sub-clinical economic losses.

Animals↗
PubMed1997

The effect of age and diet on the oral glucose tolerance test in ponies.

To evaluate the effects of age and diet on the oral glucose tolerance test (OGTT) in healthy ponies, OGTTs were performed on 2 groups of British native breed ponies (Group A: 7 foals [6-9 months], Group B: 7 mature individuals [6-13 years]) when maintained on either a high fibre pelleted ration only (Groups A and B) or a hay only diet (Group B). Plasma glucose response, following oral glucose administration, for Group A (basal plasma glucose concentration [Glu0] 4.6 +/- 0.4 mmol/l (mean +/- s.d.) increasing to 11.5 +/- 1.3 mmol/l at 90 min) was significantly different (P < 0.05) from that observed for Group B (Glu0 of 4.3 +/- 0.2 mmol/l increasing to 6.8 +/- 1.3 mmol/l at 90 min), when fed the same diet. For Group B ponies, the plasma glucose response, following oral glucose administration, was significantly different (P < 0.05) when fed hay only (Glu0 4.6 +/- 0.4 mmol/l increasing to 9.6 +/- 2.1 mmol/l at 150 min) compared to when fed the high fibre pelleted ration. These results indicate that both age and diet have a significant effect on plasma glucose concentrations measured during an OGTT.

Aging↗
PubMed1997

Nucleotide sequence of a highly conserved region of the canine p53 tumour suppressor gene.

An evolutionary conserved region of the canine tumour suppressor gene, p53, was PCR amplified and its DNA sequence determined. The 1003 bp fragment consisted of exons 5 to 8 and the intervening introns. A high level of sequence homology was demonstrated with human sequences, with the evolutionary conserved domains II, III, IV and V being identical.

Amino Acid Sequence↗
PubMed1997

Longitudinal and cross-sectional studies to evaluate the risk of sarcoid associated with castration.

In order to investigate whether gender and castration have an effect on the time to the development of sarcoids, a retrospective study in a population of donkeys was conducted using survival analysis techniques. Univariable Kaplan Meier product limit curves identified males as having significantly lower survival probability, or higher risk of developing sarcoids, than females (P < 0.01). Cox's proportional hazard model was used to assess the effect of age at entry to the population whilst simultaneously considering the effect of gender on the hazard of developing sarcoids. Age at entry and gender were both significantly associated with the hazard of sarcoid (P < 0.01). Animals younger at entry were at increased risk of being diagnosed with sarcoids and the hazard ratio for being male was 1.9. Although male animals castrated after entering the population had significantly poorer survival rates than those castrated prior to entry, this effect was not significant when age at entry to the population was fitted to the model, demonstrating that the castration procedure within the population per se was not a risk factor. Although there was a trend toward stallions being at increased risk when compared to geldings, the effect was not statistically significant, particularly when controlling for age. It was concluded that a multicentre study or meta-analysis will be necessary to resolve the issue of risk associated with castration.

Aging↗
PubMed1996

Antagonist HIV-1 Gag peptides induce structural changes in HLA B8.

In the cellular immune response, recognition by CTL-TCRs of viral antigens presented as peptides by HLA class I molecules, triggers destruction of the virally infected cell (Townsend, A.R.M., J. Rothbard, F.M. Gotch, G. Bahadur, D. Wraith, and A.J. McMichael. 1986. Cell. 44:959-968). Altered peptide ligands (APLs) which antagonise CTL recognition of infected cells have been reported (Jameson, S.C., F.R. Carbone, and M.J. Bevan. 1993. J. Exp. Med. 177:1541-1550). In one example, lysis of antigen presenting cells by CTLs in response to recognition of an HLA B8-restricted HIV-1 P17 (aa 24-31) epitope can be inhibited by naturally occurring variants of this peptide, which act as TCR antagonists (Klenerman, P., S. Rowland Jones, S. McAdam, J. Edwards, S. Daenke, D. Lalloo, B. Koppe, W. Rosenberg, D. Boyd, A. Edwards, P. Giangrande, R.E. Phillips, and A. McMichael. 1994. Nature (Lond.). 369:403-407). We have characterised two CTL clones and a CTL line whose interactions with these variants of P17 (aa 24-31) exhibit a variety of responses. We have examined the high resolution crystal structures of four of these APLs in complex with HLA B8 to determine alterations in the shape, chemistry, and local flexibility of the TCR binding surface. The variant peptides cause changes in the recognition surface by three mechanisms: changes contributed directly by the peptide, effects transmitted to the exposed peptide surface, and induced effects on the exposed framework of the peptide binding groove. While the first two mechanisms frequently lead to antagonism, the third has more profound effects on TCR recognition.

Amino Acid Sequence↗
PubMed1996

Survival analysis approach to risk factors associated with hyperlipemia in donkeys.

OBJECTIVE: To investigate the effect of gender, body condition, and age as risk factors for the development of hyperlipemia in a population of donkeys. DESIGN: Retrospective survival analysis. ANIMALS: 130 donkeys with hyperlipemia from a source population of 4,126 donkeys. PROCEDURE: A Kaplan-Meier product limit survival method was used to evaluate the effect of gender and body condition on the probability of diagnosis of clinical hyperlipemia. Cox's proportional hazard model was used to evaluate the risk of being diagnosed with hyperlipemia controlling for gender, body condition, and age at entry into the population. RESULTS: Female donkeys and donkeys of obese body condition were more at risk for developing hyperlipemia than males or those of moderate or poor body condition, respectively. None of the females in the study was pregnant. Donkeys were more likely to become hyperlipemic soon after entering the source population. Investigation of the effect of age at entry into the population indicated that older animals were at higher risk than younger animals and, controlling for age, the hazard ratios associated with being female and being overweight were 2 and 1.5, respectively. CLINICAL IMPLICATIONS: Although pregnancy and lactation are widely acknowledged as risk factors for hyperlipemia, in this population, females and obese donkeys were at highest risk, regardless of pregnancy status. Risk was greatest around the time donkeys first entered the source population. Control of body condition, reduction of stress, and close monitoring of high-risk donkeys might reduce incidences of, or allow more timely intervention for, this potentially fatal condition.

Age Factors↗
PubMed1996

Expression of transduced genes in mice generated by infecting blastocysts with avian leukosis virus-based retroviral vectors.

Transgenic mouse lines have been developed that express the tv-a receptor under the control of the chicken beta-actin promoter. These mice express the tv-a receptor in most or all tissues and in the early embryo. An avian leukosis virus (ALV)-based retroviral vector system was used for the efficient delivery of genes into preimplantation mouse embryos from these transgenic lines. Experimental animals could be generated quickly and easily by infecting susceptible blastocysts with ALV-based retroviral vectors. Expression of the delivered genes was controlled by either the constitutive viral promoter contained in the long terminal repeat or an internal nonviral tissue-specific promoter. Mating the infected founder chimeric animals produced animals that carry the ALV provirus as a transgene. A subset of the integrated proviruses expressed the chloramphenicol acetyltransferase reporter gene from either the promoter in the long terminal repeat or an internal promoter, which we believe indicates that many of the sites that are accessible to viral DNA insertion in preimplantation embryos are incompatible with expression in older animals. This approach should prove useful for studies on murine cell lineage and development, providing models for studying oncogenesis, and testing gene therapy strategies.

Actins↗
PubMed1996

Production and crystallization of MHC class I B allele single peptide complexes.

Major histocompatibility complex class I B alleles, HLA B8, B53 and B3501 have been cloned, expressed, refolded and crystallized in specific complexes with a number of different 8-mer and 9-mer peptides. For some of these crystallization was initiated by cross-seeding between different B allele complexes. All crystallize in the space group P212121, with similar unit cell dimensions of approximately 52 A X 81 A X 112 A, contain one complex per asymmetric unit and diffract to approximately 2.0 A resolution.

Alleles↗
PubMed1996

The likelihood of detecting differences between groups of sheep following deliberate infection with Ostertagia circumcincta.

An examination of variation following deliberate infection with Ostertagia circumcincta suggested that even large parasitological differences among groups have little chance of being detected unless the number of sheep in each group is quite large. Tables that give the probability for various sample sizes are presented; these tables should aid the interpretation of previously published results and may assist in the design of future experiments.

Abomasum↗