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Biomedical subjects

D M Danks

Publications and source records attributed to D M Danks.

At least 109 records · Page 6Linked to original sources
PubMed1985

Cerebro-hepato-renal (Zellweger) syndrome, adrenoleukodystrophy, and Refsum's disease: plasma changes and skin fibroblast phytanic acid oxidase.

Cerebro-hepato-renal (Zellweger) syndrome, adrenoleukodystrophy, and Refsum's disease patients can be divided into at least five distinct groups, according to the nature of their plasma changes and their fibroblast phytanic acid oxidase activities. The biochemical changes in the plasma vary from an increase in a single metabolite or group of structurally related metabolites, such as in X-linked adrenoleukodystrophy (ALD) and classical Refsum's disease, to an increase in a number of structurally distinct metabolites, as in neonatal ALD/Zellweger syndrome, and infantile Refsum's disease. All patients, with the exception of those with the X-linked form of adrenoleukodystrophy are deficient in phytanic acid oxidase activity. The great similarity observed in neonatal adrenoleukodystrophy/Zellweger syndrome and infantile Refsum's disease suggests that the basic biochemical lesion in each may be similar or at least closely related.

Adrenoleukodystrophy↗
PubMed1985

Congenital absence of pyramids and its significance in genetic diseases.

Bilateral absence of the pyramids, best assessed in transverse sections of the medulla oblongata, was found in 0.7% of 2,850 autopsies performed at the Royal Children's Hospital, Melbourne (Australia). A strong association with some forms of congenital aqueductal stenosis was observed and evaluated in further cases ascertained through other hospitals. The very strong association observed with X-linked congenital aqueduct stenosis may be useful diagnostically but must be evaluated in other centres. At least, the presence of pyramids seems strong evidence against this diagnosis. Absence of the pyramids was also observed in several known or new genetic syndromes - Meckel's syndrome, the HARD syndrome, two sisters with congenital aqueductal stenosis and polydactyly and two families with microcephaly and arthrogryposis.

Abnormalities, Multiple↗
PubMed1985

Inborn errors of trace element metabolism.

Genetic disorders of trace element transport are now known in humans, mice, dogs and cattle. Those involving copper have been known longest and are best known clinically. Effects due to copper deficiency are seen in Menkes' disease, in X-linked cutis laxa and in the X-linked series of mottled mutants in the mouse. Copper accumulation is also harmful, causing damage initially to the liver and later to the kidneys and brain in Wilson's disease, in some Bedlington terriers and in toxic milk mice. Zinc deficiency is seen in acrodermatitis enteropathica and in premature babies born to women who seem to secrete milk that is zinc-deficient, as is seen in lethal milk mice. Study of animal mutants, especially mutant mice, is helpful in understanding the human diseases and identification of the basic defects in trace element transport in these diseases is improving knowledge relevant to trace element nutrition.

Acrodermatitis↗
PubMed1985

Cutis laxa with delayed development.

Two forms of cutis laxa are well delineated. One is a dominant benign disorder in which the greatest impact is on the skin, and the second is an autosomal recessive variety with serious lung involvement and early death. A third form of cutis laxa of intermediate severity, associated with mental and growth retardation, has been described. We report seven patients with this intermediate form. All patients showed marked skin changes early in life and had some degree of mental retardation which ultimately proved less severe than it appeared at presentation. Previous reports have suggested that this disorder occurs in females and may be an X-linked dominant condition which is lethal in males. The finding of four affected males in this series makes this explanation unlikely. As consanguinity and affected sibs have been reported previously it is probably an autosomal recessive disorder.

Birth Weight↗
PubMed1985

Long term prognosis for babies with neonatal liver disease.

A total of 123 patients with neonatal liver disease without extrahepatic bile duct obstruction or arteriohepatic dysplasia have been studied for six to 18 years. Idiopathic neonatal hepatitis, present in 73 babies, carried a high mortality due to liver failure (18%), septicaemia (6%), and associated defects (14%), especially in the first year of life (25%). Progression to chronic liver disease in non-familial idiopathic cases occurred in three of 40 reviewed patients. Only 12 of these children were completely healthy, the remainder having other permanent disabilities (57%). Four of nine familial cases of idiopathic neonatal hepatitis died in the first 12 months of life as did two of the four reviewed survivors. Progression to chronic liver disease or to death was a continuous process without any interval of recovery in all but one of these patients. Among patients with a presumed infective cause, cytomegalovirus infection caused a particularly benign form of neonatal hepatitis but was a frequent cause of brain damage or other disabilities. Babies who survived other infective liver diseases showed complete healing of the liver damage. Neonatal liver disease associated with alpha 1 antitrypsin deficiency progressed to death or chronic liver disease in three of nine patients and was not associated with a paucity of interlobular bile ducts.

Chronic Disease↗
PubMed1985

A pedigree study of perinatally lethal renal disease.

A family study of perinatally lethal renal disease (PLRD) was undertaken in the State of Victoria, Australia, for the years 1961 to 1980. A total of 221 cases was ascertained through hospital and necropsy records and confirmed by necropsy findings. There were 134 cases of bilateral renal agenesis (BRA), 34 cases of unilateral agenesis with dysplasia of the other kidney (URA/RD), 42 cases of bilateral renal dysplasia (BRD), and 11 cases of renal aplasia. Parents of 131 babies were interviewed and 153 parents from 82 families had a renal ultrasound examination. In the period of best ascertainment (1975 to 1980) the frequency of PLRD was 0.27 per 1000 and of BRA 0.16 per 1000. There were 10 cases of sirenomelia, a frequency of 0.008 per 1000. For all families of PLRD, 15 of 423 (3.6%) sibs and three of 1579 (0.2%) first cousins were affected. One family had three sibs with BRA and four had two sibs with BRA. One pair of sibs and two first cousins had BRA in one and URA/RD in the other affected. One baby had BRD with an affected first cousin. The nature of the renal lesion was not established. When the index case had BRA, 14 in 283 (5.6%) sibs had PLRD. Where the index case had BRA and urogenital defects, but no birth defects in other organs, 12 of 148 sibs (8%) were affected. None of the sibs had BRA when the index case had BRA as part of a multiple malformation complex. In the multiple malformation group, however, five of 40 (12.5%) sibs had similar patterns of malformations. Renal ultrasound abnormalities were no more frequent in parents of two affected babies (one of 18) than in the other parents (nine of 135). Our findings confirm that BRA and URA are genetically related. There are a number of conclusions which are important for genetic counselling. There is a high likelihood of recurrence (8%) in sibs when the index case has BRA and urogenital abnormalities alone. When BRA is part of a multiple malformation complex, the risk of recurrence of multiple malformations is significant (12.5%), but risk recurrence of BRA is low. The finding of renal ultrasound abnormalities in the parents was not informative.

Abnormalities, Multiple↗
PubMed1985

Properties of succinic semialdehyde dehydrogenase in cultured human lymphoblasts.

A direct assay has been developed for succinic semialdehyde dehydrogenase in sonicates of human lymphocytes and Epstein-Barr Virus transformed cultured lymphoblasts. Enzyme activity was quantified by incubating cell extracts with uniformly labeled [14C]succinic semialdehyde and monitoring the conversion to [14C]succinic acid. Radiolabeled products were separated by liquid partition chromatography on hydrated silicic acid. Kinetic properties and requirements of succinic semialdehyde dehydrogenase in lymphoblast sonicates were investigated in order to determine optimal conditions for the direct assay. Enzyme activity was stimulated by dithiothreitol, ammonium and potassium ions and 0.1% Triton X-100. The concentrations for half maximal activation by ammonium and potassium were 5.2 and 13.7 mM respectively. The mean activity of succinic semialdehyde dehydrogenase in assays in which equimolar NADP+ had been substituted for NAD+ was 19% of the activity of assays which contained NAD+. Substrate Michaelis constants were 21 and 30 microM for NAD+, and 26, 42 and 70 microM for succinic semialdehyde. The enzyme displayed a pH optimum between 8 and 9 and demonstrated a slight temperature activation between 37 degrees and 45 degrees C. A deficiency of succinic semialdehyde dehydrogenase activity was documented in cultured lymphoblasts derived from a patient with gamma-hydroxybutyric aciduria.

Cell-Free System↗
PubMed1984

Cloning and sequencing of a sheep metallothionein cDNA.

A partially purified metallothionein mRNA fraction from copper-injected sheep liver was used to synthesize double-stranded cDNA, which was dC-tailed, annealed to dG-tailed pBR322 and used to transform Escherichia coli MC1061. Of the 1500 recombinant clones only one gave a positive signal when screened with a mouse metallothionein 1 probe. This clone (pSMT-1) contained an insert which included the entire coding region of a sheep metallothionein, the whole 3'-untranslated region, part of the poly(A)-tail and 25 bases of the 5'-untranslated region. DNA sequence analysis showed that this sheep metallothionein was very similar to other mammalian metallothioneins except for a threonine to proline change at amino acid 27. The clone also contained a different polyadenylation signal d(A-G-T-A-A-A) from that usually found d(A-A-T-A-A-A). Comparison of the DNA sequence of the sheep metallothionein with those of other species revealed an interesting region of homology close to the poly(A) addition signal in the 3'-untranslated region of the mRNA.

Amino Acid Sequence↗
PubMed1984

Observations on the Menkes' and brindled mouse phenotypes in cell hybrids.

Somatic cell fusion was used to study the genetic defect in Menkes' disease and in the brindled mouse mutant. Eight hybrids derived from fusion of Menkes' fibroblasts with HeLa cells and 11 hybrids between a brindled mouse fetal cell line and a mouse A9 cell were studied. The hybrids showed copper isotope uptake intermediate between the mutant and nonmutant lines and copper isotope efflux similar to that of the nonmutant parent. These results indicate that complementation studies between the mutants should be possible.

Animals↗
PubMed1984

Malonyl coenzyme A decarboxylase deficiency.

A patient is described with a deficiency of the mitochondrial enzyme, malonyl CoA decarboxylase - an inborn error of metabolism not recognized previously. The enzyme defect was first suspected because of persistent excretion of malonic and methylmalonic acids in urine in a child with repeated episodes of vomiting, some requiring hospitalization. Disturbances of lipid metabolism were demonstrated.

Acyl Coenzyme A↗