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Biomedical subjects

D J Walker

Publications and source records attributed to D J Walker.

At least 109 records · Page 6Linked to original sources

The regulation of resistance to Schistosoma mansoni by auto-anti-idiotypic immunity.

These studies explore auto-anti-idiotypic mechanisms as potential regulators of the protective immune response against Schistosoma mansoni. Anti-idiotypic responses were stimulated by immunization of mice with lymphoblasts, bearing specific idiotypic receptors. These receptors were produced in vitro by stimulation of Ag-reactive T cells by soluble cercarial immunogen, keyhole limpet hemocyanin, or Con A. The animals were then exposed to irradiated cercariae, keyhole limpet hemocyanin, or SRBC. The results indicate that the soluble cercarial immunogen lymphoblast recipient mice demonstrated reduction in a number of parameters of their immune response to schistosome Ag, including resistance to challenge by parasites. These changes were immunologically specific. Anti-idiotypic antibodies and anti-clonotypic T cell reactivity was demonstrated in the lymphoblast immunized mice. The suppression of reactivity in LBM was mediated by Lyt-1-, L3T-4-, and Lyt-2+ lymphocytes. These studies suggest that idiotypically dependent pathways might be important for the regulation of resistance to schistosomiasis.

Animals↗

Demonstration of impaired T cell regulation of Epstein-Barr virus stimulated B lymphocytes in rheumatoid arthritis with HLA identical, disease discordant sibling pairs.

Lymphocytes from patients with rheumatoid arthritis (RA) show an abnormal response after stimulation with Epstein-Barr virus (EBV), a potent B cell mitogen. In vitro IgM production from EBV stimulated lymphocytes was measured over a 21 day period. In keeping with previous studies, RA lymphocytes showed increasing IgM production between 14 and 21 days, whereas IgM production decreased during this period in normal lymphocytes (p less than 0.001). Experiments on 12 HLA identical, RA discordant sibling pairs were also undertaken. B enriched and T enriched lymphocyte populations were obtained and recombined in both an autologous and homologous manner. The abnormality in IgM production in patients with RA was shown to reside in the RA T cell population (p less than 0.005), and RA B cells combined with normal T cells behaved similarly to autologous cultures of normal B and T cells. The study shows that impaired immunoregulation of EBV stimulated B cells in RA is secondary to a functional defect in RA T cells, but no difference in the concentration of T suppressor/cytotoxic cells could be found between the disease discordant siblings. The abnormality in immunoregulation appears to be secondary to RA, rather than a product of genes encoded within the major histocompatibility complex (MHC) region, as defined by HLA-DR, A, B, and C typing.

Arthritis, Rheumatoid↗

Linkage studies of HLA and rheumatoid arthritis in multicase families.

The linkage of rheumatoid arthritis (RA) to the HLA-DR locus was investigated in 17 families with multiple cases of RA. Log odds scores were computed using the Liped program; sibship associations were examined by 2 methods. The results showed a trend toward linkage which was short of significance. The results were similar for patients with classic or definite RA, with or without the inclusion of probable RA patients. The finding of strong association and weak linkage would suggest that it is DR4, itself, that is important in RA.

Arthritis, Rheumatoid↗

Classification of rheumatoid arthritis: the importance of including data from the siblings.

A discriminant analysis has been applied to physical and laboratory data on a series of 37 patients with rheumatoid arthritis (RA). Good discrimination was found between RA when it was associated with organ-specific autoimmune phenomena and when it was not. When data from other members of the families was included there was consistently better discrimination than when using data from the patients alone. The results suggest that future studies of classification of variable diseases should include study of relatives.

Adult↗

Autoantibodies and antibodies to microorganisms in rheumatoid arthritis: comparison of histocompatible siblings.

A selection of antibodies to microorganisms were assayed on sera from a group of 12 pairs of HLA identical rheumatoid arthritis (RA) discordant siblings. Our results did not show any consistent quantitative or qualitative differences between RA and non-RA. However, autoantibodies were commoner and of higher titer in the subjects with RA. There was a difference in the antibodies to intrinsic antigens in RA which was not reflected in the antibodies to extrinsic antigens.

Antibodies, Bacterial↗

Aplastic anaemia in the Northern Region 1971-1978 and follow-up of long term survivors.

An attempt has been made to identify and review everyone who was admitted to hospital in the Northern Region between the years 1971 and 1978, and was diagnosed as having aplastic anaemia. The hospital activity analysis scheme was used as the source of the patients. Of the 537 cases recorded, the notes of 404 (75%) were traced and reviewed. We considered that 230 (57%) had been mis-classified. The incidence of aplastic anaemia was fairly constant with an average of 25 cases per year. Prognosis in the 174 cases of aplastic anaemia remaining was found to be poor with a 5-year survival of 39%. Mortality was similar in cases with an apparent cause, and those without. A follow up study of 27 long term (greater than 3 years) survivors is also reported. Seventeen (63%) had normal blood counts. There was very poor correlation between anterior iliac crest trephine findings and peripheral blood count.

Adrenal Cortex Hormones↗

Occurrence of autoimmune diseases and autoantibodies in multicase rheumatoid arthritis families.

The presence of autoimmune diseases and autoantibodies has been studied in 237 individuals from 17 families with two or more members affected by rheumatoid arthritis (RA). Hyperthyroidism occurred significantly more frequently than in a local control population (p less than 0.05), but if the RA cases were excluded this significance was lost. Thyroid cytoplasmic and microsomal antibodies were significantly more common (p less than 0.001), and this remained true if RA sufferers were excluded (p less than 0.01). The prevalence of both clinical thyroid disease and circulating thyroid autoantibodies was similar in the families where RA was associated with HLA-DR4 and in those where no DR4 association was observed. RA and immune thyroid disease may, therefore, share a common inherited factor, but this is unlikely to be at the HLA-DR locus. Antinuclear factor (ANF) was found in association with RA and with HLA-DR3 within the RA group (p less than 0.02). Relatives of RA sufferers did not show any excess of ANF positivity. The prevalence of pernicious anaemia (PA) and gastric parietal cell antibody did not differ from the expected.

Arthritis, Rheumatoid↗

Rheumatoid factor tests in the diagnosis and prediction of rheumatoid arthritis.

Four assays of rheumatoid factor (RF) have been measured on serum from 213 individuals from 13 families containing at least two sufferers from classical or definite rheumatoid arthritis (RA). Families were not uniformly RF positive or negative, and there was no evidence that non-RA RF positivity was inherited. Four individuals developed definite RA over a two year period, showing that the family members were at increased risk of RA. IgG RF and latex RF assays predicted the RA in the four cases. An association of RF positivity in RA with DR4 was observed, but this may be related to disease severity.

Arthritis, Rheumatoid↗

HLA associations are with severe rheumatoid arthritis.

Rheumatoid arthritis (RA) has been studied in 17 multicase families from the North East of England. The families comprised 281 individuals, 51 of whom had classical or definite RA, 18 had probable RA, and six were classified as previous RA. The association of classical and definite RA with HLA-DR4 was confirmed, and homozygosity for DR4 was more strongly associated than heterozygosity. There was a trend towards negative association with HLA-DR2 and DR7. Homozygosity for DR4 and possession of the haplotype most frequently inherited with RA in a particular family showed association with more severe disease. HLA-DR2 and DR7 tended to associate with less severe disease. It is therefore likely that HLA association is with the severity of disease rather than disease susceptibility.

Adolescent↗

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. Thirty-five (90%) of these possess HLA-DR4, confirming the previously reported association of RA with DR4. A further 19 individuals were found to have probable RA or gave a convincing history of previous inflammatory polyarthritis. Thirteen (68%) of these possess HLA-DR4, and this is not significantly different from non-affected family members of whom 63% possess DR4. These results suggest that HLA-DR4 is associated only with the more severe forms of RA. Homozygosity for HLA-DR4 was not associated with either earlier onset or more severe disease when compared with heterozygous DR4. Possession of the haplotype most commonly inherited with the RA in individual families was not associated with earlier onset but may be associated with more severe disease. The severity of RA appears to be influenced by the major histocompatibility complex (MHC) in these families.

Adult↗

Economic analysis of regionalized neonatal care for very low-birth-weight infants in the state of Rhode Island.

Cost-benefit analysis was utilized to evaluate the economic outcome of regionalized neonatal care in the state of Rhode Island, with specific reference to newborns weighing less than 1,500 g at birth. Two time periods consisting of two calendar years each, were analyzed: 1974 to 1975 (initiation of perinatal regionalization) and 1979 to 1980 (regionalization established). The neonatal mortality for infants weighing between 501 and 1,500 g decreased significantly between the two time periods. Neurodevelopmental morbidity was unchanged. The costs per survivor (hospital charges plus estimated costs of long-term care of handicapped survivors) were consistent over the time periods studied. The estimated benefits per survivor increased between the time periods, although this increase was not statistically significant. Benefits outweighed costs in both study periods. When one compares the economic data of 1974 to 1975 with that of 1979 to 1980, the increase in the absolute number of normal survivors since the establishment of regionalized neonatal care has resulted in benefits surpassing costs by $2 million (a greater than twofold increase). Regionalized neonatal care in the state of Rhode Island has had a positive economic outcome.

Child Development↗

Cost-benefit analysis of neonatal intensive care for infants weighing less than 1,000 grams at birth.

Cost-benefit analysis was performed on the care of 247 infants weighing between 500 and 999 g at birth, admitted to Women and Infants Hospital of Rhode Island between January 1977 and December 1981. The neonatal mortality was 68%. Eighty-seven percent of the survivors were evaluated neurodevelopmentally for 1 to 5 years: 74% were normal or minimally impaired, 10% were moderately impaired, and 16% were severely handicapped. Using these data in conjunction with cost information obtained from the hospital and therapeutic care facilities for handicapped children, total lifetime costs for the care of these infants were estimated. In 1982 dollars, present values of costs ranged from $362,992 per survivor for those weighing between 600 and 699 g to $40,647 per survivor for those weighing between 900 and 999 g, resulting in an inverse correlation between cost per survivor and birth weight (P less than .001). We estimated present values of expected lifetime earnings per survivor, with a range of zero earnings for infants between 500 and 699 g, to $77,084 for those with birth weight of 900 to 999 g. It is concluded that from the standpoint of cost-benefit analysis as was used for this study population, neonatal intensive care may not be justifiable for infants weighing less than 900 g at birth.

Adolescent↗