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Biomedical subjects

P Mackintosh

Publications and source records attributed to P Mackintosh.

At least 19 recordsLinked to original sources
PubMed1992

Transfusion associated graft versus host disease in an immunocompetent patient.

Transfusion associated graft versus host disease is a rare disorder usually confined to patients who are immunosuppressed. A case is described in a 77 year old woman who was presumed immunocompetent. She was transfused with one unit of blood from an individual who was homozygous for the same HLA haplotype as her. The diagnosis of transfusion associated graft versus host disease should be suspected in a patient who develops aplastic anaemia within 30 days of a transfusion of blood products. It is suggested that blood donations from first degree relatives should not be permitted, unless the donation is irradiated to prevent lymphocyte proliferation.

Aged↗
PubMed1990

HLA-DP and coeliac disease: family and population studies.

We investigated polymorphism of HLA-DP genes in three DR3 related diseases, confirming an association of coeliac disease with a Bgl II DP alpha polymorphism (a restriction fragment sized 3.5 kb present in 75% of patients compared to 34% of control subjects, p less than 0.001), and finding a weaker association with dermatitis herpetiformis (57% v 34%, p = 0.01) and no association with insulin dependent diabetes mellitus. The association with coeliac disease was further investigated. Msp I DP beta polymorphism was studied in 52 healthy subjects and 59 patients: a 4.9 kb fragment was present in 51% of patients with coeliac disease compared to 11.5% of control subjects (p less than 0.001). Furthermore, nearly all subjects with the DP alpha 3.5 kb fragment also had the DP beta 4.9 kb fragment. However, disease frequency was still increased in the DP alpha 3.5 positive/DP beta 4.9 negative group. In seven families, each with at least two affected members, while the DP alpha 3.5 fragment was frequently present in patients it did not preferentially segregate with any particular HLA haplotype--for example, those associated with DR3 or DR7--and therefore is not part of an extended haplotype associated with coeliac disease. We therefore conclude that a gene(s) in the HLA-DP region predisposes to coeliac disease independently of the HLA-DR/DQ regions.

Celiac Disease↗
PubMed1987

HLA and C4 polymorphism in diabetic microangiopathy.

We have reported an increased frequency of the rare B3 allotype of the fourth component of complement (C4B3) in insulin-dependent diabetics, especially in those with microangiopathy. This study has now been expanded--20 of 106 subjects with microangiopathy and 9 of 116 without possessed the C4B3 allotype (p less than 0.02). C4B3 is said to be in linkage disequilibrium with HLA-DR4. HLA typing was performed on 94 of these patients, 52 with and 42 without microangiopathy. There was no significant difference in the frequency of DR4 (62 vs 50%), DR3 (65 vs 52%), B8 (40 vs 40%) or B15 (32 vs 19%) respectively between these 2 groups. These results confirm an HLA-linked predisposition to microangiopathy, but do not determine whether the primary association is with C4B3, DR4 or another gene with which they are in linkage disequilibrium.

Complement C4↗
PubMed1986

X-linked mesangiocapillary glomerulonephritis.

Two related male patients with mesangiocapillary glomerulonephritis (MCGN) are described demonstrated by renal biopsy, inherited as an X-linked disorder. Family investigations failed to reveal any underlying immunological defects or a marker for the female carrier state. The age at diagnosis, the result of discovery of proteinuria on routine urine testing during infancy, is earlier than in any other reported cases of MCGN. This raises the possibility that this variety of MCGN may develop in utero and be detectable by alpha-fetoprotein maternal screening.

Genes, Recessive↗
PubMed1983

Gc subtypes in Northern Indians.

Isoelectric focusing was used to determine the frequencies of the Gc subtypes in a population sample from The North Indian subcontinent (now living in Birmingham, UK). The gene frequencies observed were as follows: Gc1F = 0.191, Gc1S = 0.519 and Gc2 = 0.290.243 individuals were typed and no variant alleles were detected.

Carrier Proteins↗
PubMed1981

HLA frequency and prognosis in lung cancer.

In 100 patients with lung cancer we have found no significant abnormality in overall HLA antigen frequency when compared to a control sample of 151 random health individuals from the same region, though there was a high relative risk of being HLA-BW22-positive and having lung cancer. There was an increased frequency of HLA-B5 in small-(oat-)cell anaplastic carcinomas (P less than 0.05); HLA-B15 in anaplastic tumours (P less than 0.05); HLA-B40 in Stage III patients (P = 0.05) and a decreased frequency of HLA-B12 in adenocarcinomas (P less than 0.05). In 86 patients followed up for 2 1/2-5 3/4 years after surgery we have been unable to confirm the significant association of HLA-AW19 and/or HLA-B5 with good prognosis as reported by others. The most striking observation was that the frequency of HLA-BW22 was significantly higher in patients alive at least 2 1/2 years after surgery when compared to the control groups (P less than 0.05) and 83% of patients HLA-BW22-positive are alive compared to only 52.5% of lung cancer patients lacking this antigen. However, all the P values become nonsignificant when multiplied by the number of antigens studied, and these observations need further investigation in a large, prospective study.

Adenocarcinoma↗
PubMed1981

Automation of laboratory data for hospital patients.

Computer schemes for a large automated serology service and for tissue typing and organ transplantation which are in operation in Birmingham, England, are described. Each scheme is self-contained and compact, and has been in successful operation for several years.

ABO Blood-Group System↗
PubMed1980

Another example of haemopoietic chimaerism in dizygotic twins.

Another example of haemopoietic chimaerism in dizygotic twins is described. Each twin had two distinct blood cell populations. The red cell populations differed in three blood group systems and in other genetic characters, and the white cell population in HLA types and in XX/XY karyotypes. The biological significance of these findings is discussed with special reference to the relative proportions of the two red and white cell populations, the ABH blood group gene-specified glycosyltransferase levels, and the HLA types.

Blood Cells↗
PubMed1980

Cytogenetic evidence for the localisation of the gene for congenital adrenal hyperplasia.

In the course of a study of the close linkage between the gene locus for the autosomal recessive disease, Congenital Adrenal Hyperplasia (CAH), and the major histocompatibility complex (MHC), a cytogenetic survey was undertaken. In one family, where a crossover might have occurred between some loci in the MHC complex and the locus for the 21-hydroxylase gene, there was also a crossover between the MHC locus and the centromere of chromosome 6.

Adrenal Hyperplasia, Congenital↗
PubMed1980

Suppression of mixed lymphocyte reactions by pregnancy serum.

Maternal lymphocyte function, as assessed by stimulation with cells from a human lymphoid line, is normal in pregnancy. Maternal serum, however, contains immunosuppressive factor(s), demonstrable by 29 weeks of pregnancy, and having a greater effect at 36 weeks on mixed lymphocyte reactions. These immunosuppressive factor(s) block all mixed lymphocyte reactions to the same extent and are not specific towards those stimulated by paternal antigens. Anti-B cell (dr) alloantibodies, presumably directed against foetal antigens, are not uncommon in maternal serum even in early pregnancy. There is some suggestion that the presence of these antibodies in early pregnancy is associated with selective inhibition of maternal lymphocyte stimulation by paternal antigen. No correlation was found between the presence or absence of serum suppressive factors and the clinical course of the pregnancy.

B-Lymphocytes↗
PubMed1980

The straight back syndrome.

The straight back syndrome, consisting of loss of normal upper thoracic spinal curvature associated with cardiac murmurs and radiographic cardiomegaly is considered a form of 'pseudoheart disease' which has been attributed to squashing of the heart in the reduced AP diameter of the chest. During an 18-month period 31 patients referred to a cardiologist were found to have a straight back. Forty-five relatives were subsequently examined and 27 were found also to have a straight back. Palpitations and chest pain were the commonest symptoms. On the lateral chest radiograph the distance from the middle of the anterior border T8 to a vertical line connecting T4 and T12 was found to be significantly reduced compared to controls, and a value less 1.2 cm is indicative of a straight back. Of the 58 subjects with the syndrome, 39 (67 per cent) had clinical and/or echocardiographic evidence of mitral valve prolapse. Respiratory function testing revealed no significant abnormality. HLA typing showed no association with an particular HLA antigen but indicates that the straight back syndrome is inherited as an autosomal dominant condition and suggested that the antigenic determinants may be located on chromosome 6. We conclude that the straight back syndrome should no longer be considered a form of pseudoheart disease and patients should be investigated for associated mitral valve prolapse and their relatives screened.

Adolescent↗