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Biomedical subjects

D C Kilpatrick

Publications and source records attributed to D C Kilpatrick.

114 records · Page 7Linked to original sources
PubMedDate not supplied

Influence of human leukocyte antigen and tumour necrosis factor genes on the development of pre-eclampsia.

Pre-eclampsia is a syndrome with a strong familial component. Autosomal recessive inheritance acting only in the mother is not consistent with the epidemiological data, and a more complex genetic susceptibility, involving interactions between maternal and fetal genomes, seems likely. The human leukocyte antigen (HLA) system has been implicated, but many of the findings reported have been inconsistent or contradictory. Pre-eclampsia is unlikely to be the simple result of excessive HLA-class II antigen sharing between mother and fetus, as was first thought, but a more complex mechanism involving feto-maternal compatibility cannot be excluded. The reported increase in HLA-DR4 in mothers and babies from pre-eclamptic pregnancies has not been independently confirmed for mothers, and no further studies have been conducted with babies. Consequently, the allegedly stronger relationship with HLA-DR4 sharing between mother and fetus has neither been confirmed nor refuted. Certain (B44-DR7)-containing haplotypes appear to confer increased risk for pre-eclampsia on the basis of independent analyses of American and Scottish populations. HLA-DR53 may be associated with the antiphospholipid antibody syndrome, which is itself a strong risk factor for pre-eclampsia. The tumour necrosis factor (TNF)-alpha allele, TNF1, may be associated with pre-eclampsia and certainly elevated concentrations of the cytokine appear to be a feature of the disease. The inducibility of TNF-alpha is HLA-class II-dependent, and the relevance of HLA-class II genes might be entirely in relation to TNF-alpha synthesis and secretion.

Antiphospholipid Syndrome↗
PubMedDate not supplied

Is there a relationship between HLA type and prognostic factors in breast cancer?

No convincing association exists between HLA type and breast cancer development but certain HLA types have been suggested to be associated with poor risk disease. Here, the HLA type (class I and II) for 141 breast cancer patients was compared to a control population of 100 individuals and to the prognostic indicators for the patients. No association was found between HLA type and breast cancer development. Consideration of individual HLA/prognostic factor relationships previously reported confirmed that HLA-B7 was over-represented in premenopausal oestrogen-receptor (ER)-positive, grade 3 tumours (p = 0.04) and that HLA-A1 correlated positively with Nottingham Prognostic Index (p < 0.05) and with ER-negative disease (p < 0.05). These findings suggest that some previously identified associations between HLA type I and particular prognostic factors may be real, if weak but appear to conflict with the only other sizeable study investigating HLA type II in breast cancer (which negatively correlated HLA-DR 11 with early onset disease).

Adult↗
PubMedDate not supplied

HLA antigen frequencies in children born to HIV-infected mothers.

Tissue-typing for HLA-A, B, and DR antigens was carried out on 53 babies, 47 of them unrelated, born to mothers known to be HIV-infected from intravenous drug usage or sexual contact with drug users. These babies were followed up to assess whether HLA phenotype was associated with vertical transmission of HIV infection or disease progression. Of the 47 unrelated babies, eight became infected with HIV. The frequency of HLA-DR3 was three times higher in the HIV-positive infants compared to the HIV-negative infants (43 per cent vs 15 per cent) in our study population. Conversely, HLA-A3 was three times less common in the HIV-positive infants (12.5 per cent vs 42 per cent). A comparison of HLA antigens between our study group babies and babies born to healthy mothers unselected for HIV status revealed higher proportions of HLA-B18, B7, and DR2 in the study group. Moreover, the combination, A3, B7, DR2 was four times commoner in our study population relative to controls (RR = 3.9; p less than 0.003), but was found only in babies who were not HIV infected. The combination A1, B8, DR3, in contrast, was found less often than expected in our study group (RR = 0.39) and was disproportionately represented amongst the infected babies. We have observed an unexpectedly low (6 per cent) mother-to-infant transmission rate of HIV among prospectively studied intravenous drug users. We speculate that the unusually high ratio of the common antigen combinations (often halotypes), A3, B7, DR2 to A1, B8, DR3 in this population may be contributory.

HIV Infections↗
PubMedDate not supplied

Immune profile of women experiencing recurrent spontaneous abortions of unknown aetiology.

Immunological and immunogenetic investigations are described in a group of 28 women with a history of unexplained recurrent (greater than or equal to 3 consecutive) spontaneous abortions (RSA). Compared with female blood donor controls, recurrent aborters had significantly elevated mean serum complement C4 (p less than 0.05), but not C3, levels. Immunoglobulin levels and T4:T8 ratios showed a similar distribution to the controls. Mixed lymphocyte reactivities to partners' lymphocytes were low in some of the patients, but hyporesponsiveness correlated well with husband-wife HLA-DR compatibility. No individual HLA specificity was significantly increased in the RSA patients, but the combination A3, B7, DR2 was common (p less than 0.02), and general HLA antigen sharing with partners was significantly increased (p less than 0.004) relative to obstetrically normal couples. RSA women who shared two or more HLA antigens with spouses had higher mean serum immunoglobulin concentrations, which for IgM reached statistical significance (p less than 0.05).

Abortion, Habitual↗
PubMedDate not supplied

Mannan-binding protein in human umbilical cord blood.

Mannan binding protein (MBP) may be important for host defence particularly in infancy. MBP concentration was measured in 237 umbilical cord blood samples from singleton pregnancies and compared to those of 352 blood donors. Both data sets yielded a bimodal frequency distribution, consisting of a log-normal peak and a long tail of lower values. The range (0-23 U/ml) and median (7.2 U/ml) of cord blood values were significantly lower than those of blood donors (range 0-43 U/ml; median 8.3 U/ml). MBP was also measured in the cord blood samples of 8 pairs of twin siblings. Discordant values in two pairs of twins suggest that cord blood MBP is derived from the fetoplacental unit and not from the maternal circulation by transplacental passage.

Adult↗