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Biomedical subjects

D M Danks

Publications and source records attributed to D M Danks.

At least 127 records · Page 7Linked to original sources
PubMed1983

Mutations in humans and animals which affect copper metabolism.

Various inherited disorders of copper metabolism in man and animals are reviewed. Emphasis is placed on the use of cultured cells from mutants to determine the primary molecular defects and to acquire basic knowledge of normal copper metabolism. This allows better diagnostic tests and possible treatment of the disorders. Menkes' disease in humans and mottled mouse mutants are discussed in detail, as they illustrate these approaches.

Animals↗
PubMed1983

Immunological evidence for an ornithine transcarbamylase lesion resulting in the formation of enzyme with smaller protein subunits.

An unusual form of ornithine transcarbamylase deficiency was found in a male child who became unconscious at 8 months. Two maternal uncles had died during similar illnesses at 6 years and 11 years, respectively. Detailed studies of the enzyme showed 10% residual activity, a very low Km for carbamyl phosphate (0.015 mmol/l) and near normal amounts of immunoreactive protein with a smaller than normal subunit (molecular weight 37 800 instead of 39 700). This information was obtained from a 10 mg liver biopsy core using protein separation on SDS-polyacrylamide gel, electrophoretic transfer to nitrocellulose filters and probing with antibody to the enzyme. Resolution of the exact mutation causing this change will be of interest to those who are studying the processing of mitochondrial enzymes during transport from the cytoplasm.

Carbamyl Phosphate↗
PubMed1983

Thoracic-pelvic dysostosis: a 'new' autosomal dominant form.

A form of thoracic and pelvic dysostosis is reported in a mother and her son. The short ribs caused respiratory distress in the baby and raised the possibility of asphyxiating thoracic dystrophy (ATD). The radiological features, however, distinguish this benign condition from ATD and other described skeletal dysplasias.

Adult↗
PubMed1983

Mutations at more than one locus may be involved in cystic fibrosis--evidence based on first-cousin data and direct counting of cases.

Cystic fibrosis was present in 35 of 5,265 first cousins of index cases with the disease. The gene frequency was estimated to be .0281 +/- .00544, using an improved method that allows for the influence of cousin sibship size upon the estimate. This figure is higher than that obtained by direct counting of cases in Victoria, Australia, from 1955-1979 (.0198 +/- .000127), raising the possibility that multiple gene loci may be involved in this disease. Further analysis showed that the number of affected first cousins fitted very well with an expected number based on a model involving two gene loci, each responsible for half the cases of cystic fibrosis. Agreement with expectations based on a single locus was not good. An alternate explanation of gross underascertainment of cases is dismissed because the index sibships were shown to fit very closely a truncate binomial distribution. The gene frequencies at the putative two loci would then each be .0140 and heterozygote frequencies one in 36. One in 18 people would be heterozygous at either one or the other of the loci.

Adult↗
PubMed1982

Copper metabolism in mottled mouse mutants. The effect of copper therapy on lysyl oxidase activity in brindled (Mobr) mice.

Lysyl oxidase activity in extracts of skin from 1-day-old Mobr/Y mice was found to be between 50 and 60% of that in corresponding extracts from littermate +/Y mice of the same age. It was increased to 84-150% of that in the latter by prior treatment of the Mobr/Y mice at 7 days of age with a single subcutaneous injection of 50 micrograms of copper, retained as Cu+ in an alkyl polyether/sebacic acid solution. This suggests that in this form the copper is able to by-pass the block in copper metabolism and is deliverable to copper-requiring processes.

Amino Acid Oxidoreductases↗
PubMed1982

Carrier detection in ornithine transcarbamylase deficiency.

We have studied six known heterozygotes for ornithine transcarbamylase (McKusick 31125; OTC) deficiency. All had abnormal results when tested by measurement of urine orotic acid after protein loading. Duodenal mucosa OTC assay detected fewer of the known heterozygotes but was a useful supplementary test. Urine orotic acid excretion after protein loading is influenced by age and results from women being tested must be compared with those from controls of appropriate age.

Adolescent↗
PubMed1982

Normal hydroxylation of proline in collagen synthesized by skin fibroblasts from a patient with prolidase deficiency.

The extent of hydroxylation of proline in collagen synthesized and secreted into the culture medium by skin fibroblasts derived from a patient with prolidase deficiency has been examined and found to be normal. It would seem likely that to a considerable extent the urinary proline-containing dipeptides apparent in this condition are derived from sources other than collagen.

Adult↗
PubMed1982

beta-hydroxyisobutyryl coenzyme A deacylase deficiency: a defect in valine metabolism associated with physical malformations.

An infant, born to parents who were first cousins had multiple physical malformations. An associated biochemical abnormality was suggested by the urinary excretion of cysteine and cysteamine conjugates of methacrylic acid. The coenzyme A (CoA) ester of this compound is an intermediate in the pathway of valine oxidation. Subsequent investigation revealed a deficiency of beta-hydroxyisobutyryl-CoA deacylase, an enzyme unique to valine metabolism. The enzyme defect results in accumulation of methacrylyl-CoA, a highly reactive compound, which readily undergoes addition reactions with free sulfhydryl groups. Tissue damage due to reactions between methacrylyl-CoA and important sulfhydryl-containing enzymes and cofactors may account for the teratogenic effects seen in this patient.

Abnormalities, Multiple↗
PubMed1981

Heterogeneity of the molecular defect in human dihydropteridine reductase deficiency.

Radioimmunoassay, immunoprecipitation, affinity chromatography and two-dimensional gel electrophoresis were used to test cultured cells from three families with dihydropteridine reductase deficiency for a catalytically incompetent product of the mutant gene. No mutant enzyme was detected in one dihydropteridine reductase-deficient homozygote or in her parents. A second homozygote and both her parents had easily detectable concentrations of inactive mutant enzyme. In a third family one parent fitted into each of these categories.

Cells, Cultured↗