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A F Wright

Publications and source records attributed to A F Wright.

122 records · Page 7Linked to original sources

DNA probes in X-linked retinitis pigmentosa.

Informative members of more than twenty families with X-linked retinitis pigmentosa have been sampled by venipuncture and DNA extracted from peripheral blood leucocytes and lymphoblastoid cell lines. X chromosome-specific recombinant DNA probes have been isolated from an X chromosomal genomic DNA library obtained by flow-sorting human chromosomes. These, and similar probes obtained from other laboratories, are being used to identify restriction fragment length polymorphisms in retinitis pigmentosa obligate heterozygotes. By analysis of linkage relationships in the offspring of double heterozygotes, it may be possible to localize the gene(s) responsible for this disorder to a particular subregion of the X-chromosome. Such probes are potentially useful for carrier detection and prenatal diagnosis.

Adolescent↗

Comparison of the properties of histidine ammonia-lyase in normal and histidinemic mutant mice.

The histidinemic (his/his) mutant mouse shows greatly reduced skin and liver histidine:ammonia-lyase (HAL; EC 4.3.1.3) activity compared with normal mice. Liver HAL activity in the mutant is heat and salt labile and is inhibited at high substrate concentrations. Two HAL components have been identified in the normal mouse liver, a minor component with properties similar to those of HAL of the mutant mouse and a major component which is heat and salt stable and insensitive to substrate inhibition. Immunotitration with anti-HAL antibody shows that the livers of mutant mice contain no detectable antigenically cross-reacting HAL protein. It is concluded, therefore, that the his allele is a null allele at a structural or regulatory locus for the major HAL enzyme and maps close to the HAL-regulatory locus Hsd and that te low residual HAL activity in the mutant is due to another enzyme.

Alleles↗

Genetic factors in puerperal affective psychoses.

The hypothesis that puerperal affective psychosis (PAP) is genetically related to manic-depressive disorder was tested by comparing the morbidity risks for puerperal and non-puerperal affective disorders in the relatives of 17 PAP subjects and 20 parous manic-depressives (PMD) with no history of puerperal illness. The risk for affective disorder (mania, depression or suicide) and puerperal affective disorder was the same in the two groups of relatives and the test hypothesis was accepted, although the sample size was small. The frequencies of HLA-A, B and C locus antigens, nine blood group antigens and 10 red blood cell isoenzymes were not significantly different in the PAP and PMD subjects, showing that in this series genetic markers do not distinguish puerperal from non-puerperal affective psychoses.

Adult↗

How women felt about their sterilization--a follow-up of 368 patients in a general practice.

As a sequel to a questionnaire survey of sterilized patients in a general practice, 368 women were interviewed to assess outcome. Two hundred and ninety-two (79.3 per cent) were pleased with the operation and 76 (20.7 per cent) expressed regrets, though more than half of these (56.6 per cent) said they thought they would have chosen the operation again in the same circumstances. Of the women who were 30 years or over at time of operation, 14 per cent expressed regrets, compared with 39 per cent who were sterilized under 30 years of age (p<0.001). The regretful women were also more likely to have had clinical indications for operation, major contraceptive problems before operation, a history of attempted suicide and were less likely to have discussed vasectomy (p<0.05). The main changes reported after sterilization were a worsening in menstruation for 154 (42.2 per cent) and improvement in sex life for 133 (36.2 per cent) and in family life for 137 (37.2 per cent).

Adult↗

The use of biochemical methods for detecting changes in cell population of rat bone marrow.

The in vitro incorporation of 14C-glycine into haem, and 35S-sulphate into macromolecules have been investigated as biochemical measurements with the potential to reflect the proportion of certain erythroid and myeloid cells within rat bone marrow. Erythroid hyperplasia caused an increase of haem synthesis and a concomitant decrease in 35S-sulphate incorporation. Erythroid hypoplasia reduced haem synthesis and increased 35S-sulphate incorporation. The measures of haem synthesis and 35S-sulphate incorporation thus provide useful tools for detecting specific changes in cell populations in rat bone marrow suspensions.

Animals↗

Antitumor effects of an antibody-carboxypeptidase G2 conjugate in combination with a benzoic acid mustard prodrug.

The F(ab')2 fragment of the antitumor monoclonal antibody, A5B7, was covalently linked to the bacterial enzyme carboxypeptidase G2 (CPG2). The resulting conjugate was used in combination with a prodrug of a benzoic acid mustard alkylating agent to treat human colon tumor xenografts in a two-step targeting strategy, antibody-directed enzyme prodrug therapy (ADEPT). The prodrug, 4-[(2-chloroethyl) (2-mesyloxyethyl)amino]-benzoyl-L-glutamic acid is rapidly converted by CPG2 to a drug that is at least 15x more toxic in vitro against LS174T colorectal tumor cells than the prodrug. Optimal tumor/blood ratios of the A5B7-CPG2 were achieved 72 h after administration of the conjugate to athymic mice bearing established LS174T tumor xenografts. Significant antitumor activity was seen in LS174T tumor-bearing mice treated with the conjugate followed 3 d later by the prodrug. In contrast, prodrug, conjugate, or active drug alone did not result in any antitumor activity in this tumor model. These studies demonstrate the advantage of a two-step ADEPT system for the treatment of colorectal cancer.

Animals↗

Cation transport in lymphoblastoid cell lines established from bipolar manic-depressive patients.

Lymphoblastoid cell lines established from patients suffering from bipolar manic depression have been used to study the possible involvement of cation transport in the aetiology of this illness. No significant difference was found in the K+ fluxes mediated by the ouabain-sensitive sodium pump, the diuretic-sensitive cotransport system and the passive leak pathway of cell lines established from either control or bipolar subjects. The mean value for the specific binding of 3H-ouabain (sodium pump site number) was significantly higher in the bipolar group (approximately 30%) than in the control group.

Adult↗

Close genetic linkage between X-linked retinitis pigmentosa and a restriction fragment length polymorphism identified by recombinant DNA probe L1.28.

Retinitis pigmentosa (RP) is a group of retinal degeneration characterized by progressive visual field loss, night blindness and pigmentary retinopathy. Its prevalence is in the region of 1-2 in 5,000 of the general population, making it one of the commoner causes of blindness in early and middle life. Although 36-48% of RP patients are isolated cases, the remainder show autosomal dominant, autosomal recessive or X-linked modes of inheritance. The X-linked variety ( XLRP ) is found in 14-22% of RP families in the UK. In the present study, X chromosome-specific recombinant DNA probes which can detect restriction fragment length polymorphisms have been used to localize the XLRP gene(s) to a subregion of the X chromosome using linkage analysis. One of the probes, L1.28, has been shown to be closely linked to XLRP in five kindreds, with 95% confidence limits of 0-15 centimorgans (maximum LOD score of 7.89 at a distance of 3 centimorgans). This suggests that the XLRP locus lies on the proximal part of the short arm of the X chromosome. This probe is potentially useful for carrier detection and early diagnosis in about 40% of cases, provided that genetic heterogeneity can be excluded by analysis of further families.

Chromosome Mapping↗