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Biomedical subjects

D W Cooper

Publications and source records attributed to D W Cooper.

At least 91 records · Page 5Linked to original sources

Progression of HIV-related disease is associated with HLA DQ and DR alleles defined by restriction fragment length polymorphisms.

A cohort of 139 hemophiliacs was typed for HLA D region genes by means of restriction fragment length polymorphisms (RFLPs) detected by HLA DQ and DR gene probes. Disease progression was studied in the 65 HIV antibody-positive patients, who were infected by contaminated clotting factor before 1985. Strong associations were found between disease progression in HIV-infected patients and allelic DNA fragments revealed by a DQ alpha cDNA probe. A 5.5 kb fragment was reduced in frequency and a 4.6 kb fragment increased in frequency (p less than 0.005) in the faster progressing group, as measured both by development of CDC Category IV clinical symptoms and CD4 number less than 200 x 10(6)/l. These results correlate with DR types deduced from the RFLP patterns revealed by DR beta and DQ alpha gene probes. A decrease in DR4 and an increase in both DR5 and the DR3 subtype found in the A1 B8 DR3 haplotype were associated with disease progression (p less than 0.05).

Alleles↗

Absence of close linkage between maternal genes for susceptibility to pre-eclampsia/eclampsia and HLA DR beta.

To test the possibility that maternally expressed susceptibility genes for pre-eclampsia/eclampsia are closely linked to the HLA region on chromosome 6 of the human genome, members of ten pedigrees with multiple cases of these disorders were typed for HLA DR beta restriction fragment length polymorphisms by means of TaqI digests. The data were analysed by the LIPED program to calculate lod scores, by several programs to detect potential heterogeneity of recombination fraction between pedigrees, and by the affected-sibling and the affected-pedigree-member methods. The results exclude close linkage. If the putative susceptibility genes lie on chromosome 6 they must lie at least 5 centiMorgans, and probably more, from the HLA DR beta loci. No indication of linkage at higher recombination fractions was found. The main maternally expressed genes affecting susceptibility to pre-eclampsia are not in the HLA region.

Adult↗

Immunoglobulin G levels in fetal and newborn tammar wallabies (Macropus eugenii).

Immunoglobulin G (IgG) was measured in fetal, neonatal and colostral samples from the tammar wallaby (Macropus eugenii) in order to study the possibility of passively acquired immunity. Samples were obtained from young at a known stage of gestation and at known times (to the minute) after birth. IgG was present (in increasing levels of concentration) in fetal serum, neonatal serum and colostrum. Since the fetus and neonate are probably unable to make immunoglobulin (Ig), it is hypothesized that transplacental and trans-gut transmission takes place from mother to offspring. The vascular yolk sac placenta has a high concentration of IgG, and is the most likely route of transmission from mother to young. Some observations were made of IgA which was found only in colostrum. No Ig of either kind was found in yolk sac fluid.

Animals↗

Linkage studies of HLA and insulin gene restriction fragment length polymorphisms in families with IDDM.

Linkage analysis of HLA DR antigen as well as DR and DQ restriction fragment length polymorphism (RFLP) data using the LIPED computer program and various three-allele disease locus models showed very close linkage to an insulin-dependent diabetes mellitus (IDDM)-susceptibility locus. RFLP data alone were equal or superior to conventional HLA antigen typing in the linkage analysis. Insulin gene restriction fragment data were analyzed for evidence of either a susceptibility locus linked to the insulin gene or an effect of alleles at the insulin locus on the HLA-linked susceptibility gene. No evidence was found of any effect of the insulin gene, and it is suggested that alternative explanations of the reported population associations between the insulin gene and IDDM should be considered.

Computer Simulation↗

No association between the ovine leucocyte antigen (OLA) system in the Australian merino and susceptibility to Haemonchus contortus infection.

A genetic analysis has been made of the Ovine Leucocyte Antigenic (OLA) system in Australian merinos. The animals consisted of sires, dams and their progeny. The typing data were consistent with previous findings of a high degree of polymorphism. At least two closely linked loci with several alleles at each are necessary to explain the data. No evidence was found for an association between OLA types and three measures of susceptibility to infection by the blood-sucking parasite Haemonchus contortus. Attention is drawn to the utility of half-sib data for analysis of the genetic control of resistance to parasites in sheep and other animals with a similar breeding structure.

Animals↗

A marsupial phosphoglycerate kinase (PGK) processed pseudogene.

A clone that cross-hybridized with a full-length human cDNA PGK probe was isolated from a hill kangaroo (Macropus robustus: Marsupialia) lambda EMBL4 EcoRI genomic library. The clone was sequenced and demonstrated to be a pseudogene, with two deletions (one of 3 bases, the other 24 bases long), one single base insertion, and a nonsense mutation with respect to the functional human X-linked gene. It is flanked by terminal repeats in the 5' and 3' noncoding regions, but it has no 3' poly(A) remnant. The 3' untranslated region has a 34-bp sequence, with 29 bp homologous to the human 3' untranslated region. The overall percentage homology with the mouse and human X-linked PGK indicates that this pseudogene is probably more closely related to eutherian X-linked PGK genes than to the autosomal form. The results also suggest that pseudogenes are of considerable antiquity (greater than 100 MYr) in the mammalian lineage.

Animals↗

Genetic control of susceptibility to eclampsia and miscarriage.

An analysis has been made of 48 pedigrees selected (ascertained) through an affected mother in the first generation. These pedigrees mainly involve cases of eclampsia which occurred before its recent decline in incidence. The data confirm the genetic determination of susceptibility indicated by published data on eclampsia/preeclampsia. There is a suggestion that the fetal genotype can contribute to susceptibility to eclampsia in its mother, in contrast to previous findings that susceptibility to pre-eclampsia is controlled solely by the maternal genotype. An association between eclampsia and miscarriage is shown in the data. We argue that this suggests that the primary mode of action of the gene(s) involved is to affect the interaction between uterine and placental tissue.

Abortion, Spontaneous↗

Lack of evidence for complement-dependent cytotoxic antibodies to fetal paternally derived antigens in the marsupial Macropus eugenii (tammar wallaby).

A total of 241 serum samples from 145 parous tammar wallabies (Macropus eugenii) were screened for presence of antibodies to paternally derived antigens of the fetus. These samples were taken at different stages in late pregnancy after placental contact was intimate and after birth. Complement-dependent cytotoxicity tests were unable to detect any specific antibodies. It is concluded that the yolk sac placenta of M. eugenii does not allow intimate enough contact between fetal tissues and the maternal circulation to induce formation of cytotoxic antibodies by its mother. This is in contrast to eutherian mammals, in which such production of cytotoxic antibodies occurs frequently as a result of pregnancy. Together with other data it is suggested that the short implantation period in M. eugenii, which is common to all marsupials, has probably not evolved to prevent maternal immune attack upon the conceptus.

Animals↗

C3 allotypes in pregnancy hypertension and eclampsia.

C3 allotyping has been performed on 424 Australian women, 203 with normotensive pregnancies, 161 with hypertensive noneclamptic pregnancies and 60 eclamptic women. The frequency of women heterozygous for 'rare' C3 alleles was 1% in the normotensive women and 3.7% in the hypertensive group. Three out of 25 (12%) of the women with proteinuric hypertension in pregnancy carried 'rare' C3 alleles. This suggested the hypothesis that pre-eclampsia/eclampsia is associated with a higher frequency of rare alleles. The sample of 60 eclamptic women collected to test the hypothesis had no rare alleles, refuting the hypothesis. The frequency of the common (C3F, C3S) alleles did not differ significantly between the three groups. We conclude that there is no evidence for any association between susceptibility to eclampsia and allotypes of the C3 complement component.

Complement C3↗

High mobility group (HMG) proteins in the tammar wallaby Macropus eugenii: quantitative variations between tissues and testis-specific co-extracted proteins.

1. Tammar wallaby (Macropus eugenii, Marsupialia) proteins with similar electrophoretic mobilities to calf non-histone chromosomal proteins HMG 1, 2, 14 and 17 are perchloric acid extracted from whole tissues (liver, kidney, spleen, brain and testis) and purified liver nuclei (using PCA or 0.35 M NaCl). 2. Tammar and calf HMG 1 have similar amino acid compositions. 3. Two testis-specific basic proteins co-extracting with HMG-like proteins from both tammar and red kangaroo (Megaleia rufa) are found in whole testis, purified testis nuclei, but not epididymis. 4. Tammar HMG 2 separates into two components on both acid urea and SDS gels. The larger, more basic protein, HMG 2b, is relatively abundant in proliferating tissues (testis, spleen).

Amino Acids↗

Genetics of hypertension in pregnancy: possible single gene control of pre-eclampsia and eclampsia in the descendants of eclamptic women.

Our report concerns the incidences of pre-eclampsia and eclampsia in 147 sisters, 248 daughters, 74 granddaughters, and 131 daughters-in-law of women who have had eclampsia. The disorder is highly heritable. We have analysed the data in two ways, firstly, as a single gene condition and, secondly, as a multifactorial condition. The observed incidences fit closely with the single gene model with frequency of the putative gene being 0.25. When Falconer's method of estimating heritabilities of discrete characters is used, estimates of 120% (sisters), 88% (daughters), and 105% (granddaughters)--none significantly different from 100%-are obtained. Insofar as possible, our definition of pre-eclampsia corresponds with EPH in the descriptive classification of the Organisation Gestosis and to 'severe pre-eclampsia' in Nelson's classification. The women were delivered in many different hospitals, however, and many records fail to provide all of the essential information.

Eclampsia↗