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Biomedical subjects

P Mackintosh

Publications and source records attributed to P Mackintosh.

36 records · Page 2Linked to original sources

Recurrent bacterial meningitis in patients with genetic defects of terminal complement components.

Isolated genetic deficiencies of complement components in man are rare. We describe two kindreds with inborn deficiencies of either C5 or C6 in which both propositi presented with recurrent bacterial meningitis. Neisseria meningitidis was isolated from the cerebrospinal fluid of the C5-deficient patient and bactericidal activity against his autologous meningococcus was absent from whole fresh patients' serum despite a rising titre of complement-fixing antibody. The stimulated movement of normal leucocytes was impaired in the presence of C5-deficient serum but not in the presence of C6-deficient serum; neither deficiency reduced significantly the complement-dependent opsonization of Saccharomyces cerevisiae. HLA typing and complement component phenotyping showed no segregation with the complement defect in either the C5- or C6-deficient families. Normal individuals and apparent heterozygotes with approximately half the normal levels of the relevant component were found in both families, in keeping with an autosomal codominant inheritance of the defects.

Adult↗

HLA haplotypes and hayfever: a possible protective role.

The HLA haplotype frequencies of European asthmatic children and their immediate families were studied, and a disassociation between haplotype A1-B8 and skin sensitivity to grass pollens was found, suggesting that within this allergic population, possession of the haplotype A1-B8 conferred possible protection against grass pollinosis. There was no association between A1-B8 and clinical asthma or between it and skin sensitivity to the house dust mite.

Dust↗

HLA antigens and certain types of uveitis.

Some preliminary results are given on human leucocyte antigen (HLA) typing of nine patients with sympathetic ophthalmitis, two with Vogt-Koyanagi-Harada disease, and nine with Behçet's disease and uveitis. In the sympathetic ophthalmitis patients the relative risk for B40 was 7.2, which would indicate that a more extensive study might be valuable. In Behçet's disease B5 and B27 both carried increased risks of 9.4 and 11.1 respectively.

Behcet Syndrome↗

Results of 250 consecutive cadaver kidney transplants.

The results of 250 cadaver kidney transplants performed at this hospital between May 1968 and December 1974 were analysed. A functioning transplant was defined strictly as one that maintained the recipient in good health with a serum creatinine below 442 mumol/1 (5 mg/100 ml) without any need for dialysis. The proportions of kidneys functioning after one, two, and three years were 40-4%, 33-9%, and 31-1% respectively, the corresponding survival rates of patients being 62-6%, 57-4%, and 43-8%. The primary failure rate overall was 21-6%, while the failure rates for first, second, and third transplants were 18-1%, 39-9%, and 66-7% respectively. Half of the primary failures were attributed to the use of cadaver kidneys with abnormal vasculature or long ischaemic times or originating from non-ventilated donors. Of the initially successful transplants 49% were subsequently lost due to rejection (53%) or death of the patient with a functioning transplant (46%), and of the secondary losses 58% occurred within three months of transplantation. HLA matching of donor and recipient for two or more antigens was associated with a significant increase in transplant survival--46% at three years as opposed to 9-5% at three years for kidneys with poorer matches.

Adolescent↗

Serological identification of Ia antigens: report of a British region Ia workshop.

In preparation for the 7th International Histocompatibility Workshop 13 laboratories in the British Region participated in a local workshop. One hundred and twenty-three sera which had been previously shown to have activity on either normal B cells, CLL cells or B cell lymphoid lines in the absence of HLA-A, B or C activity were exchanged between the laboratories. These sera were tested on a total of 212 B cells, 101 CLL cells, 76 T cells and 76 lymphoid cell lines. The data was collected and analyzed in Oxford. The analysis showed that six groups of sera could be distinguished. When these groups were compared with the D locus typing of some of the lymphoid lines which were derived from individuals used as MLC typing cells, they were seen to have significant associations with D locus antigens. The serological groups defined were therefore given numbers corresponding to the D locus numbers they associate with, i.e. UK1 is associated with DW1 and so on for UK2, 3, 4, 5 and 7. Comparison of typing techniques showed that long incubation both with antiserum and then with complement, 1 hour + 2 hours gave the best and most reproducible reactions on normal B cells. Residual anti-HLA-A, B or C activity in some of the sera even after platelet absorption showed the importance of adequate checking on T cells after absorption.

Antibody Specificity↗

Histocompatibility antigens in inflammatory bowel disease. Their clinical significance and their association with arthropathy with special reference to HLA-B27 (W27).

Histocompatibility (HLA) antigen phenotypes have been studied in 100 patients with ulcerative colitis, 100 with Crohn's disease, and 283 normal controls. In addition the incidence of ankylosing spondylitis, sacroiliitis, and "enteropathic" peripheral arthropathy was determined in the patients with inflammatory bowel disease (IBD). There was no significant difference in antigen frequency between patients and controls. However, the incidence of HLA-B27 was increased in the patients complicated by ankylosing spondylitis and/or sacroiliitis in both ulcerative colitis and Crohn's disease. In contrast, none of the 29 IBD patients with "enteropathic" peripheral arthropathy had B27 antigen. Furthermore, ankylosing spondylitis was found more frequently in ulcerative colitis bearing HLA-B27 compared with non-B27 patients (P less than 0-01). The same was found in Crohn's disease, although this difference was not statistically significant. In addition, 12 of 14 ulcerative colitis patients and five out of six Crohn's patients with HLA-B27 had total colitis, compared with the frequency of total colitis in non-B27 patients (P less than 0-024 and less than 0-03 respectively). The data suggest that B27 histocompatibility antigen could be a pathogenetic discriminator between the arthropathies in IBD and may be of prognostic significance with respect to extension and severity of the disease.

Arthritis↗

A search for linkage in cystic fibrosis.

Linkage between the locus for cystic fibrosis and other genetic markers was explored in 40 families from Birmingham and 20 from Manchester. No strong evidence was found for linkage with any of the markers examined. There was evidence against close linkage with ABO, HLA, and Rh.

Child↗