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Biomedical subjects

A E Harding

Publications and source records attributed to A E Harding.

At least 199 records · Page 11Linked to original sources
PubMed1989

Genetic heterogeneity and mitochondrial DNA heteroplasmy in Leber's hereditary optic neuropathy.

Analysis of mitochondrial DNA from patients with Leber's hereditary optic neuropathy and their relatives showed that the previously reported mutation at base pair (bp) 11778, shown by loss of a recognition site for the restriction endonuclease SfaNI, was present in only four out of eight families. This mutation was associated with a poor prognosis for visual recovery, whereas four of five affected males without the 11778 bp mutation followed for four years or more had regained useful vision. All but one of the subjects showing the SfaNI site loss had a variable mixture of mutant and normal mitochondrial DNA in peripheral blood, and the relative proportions appeared to be correlated with the risk of developing or transmitting Leber's hereditary optic neuropathy.

Adult↗
PubMed1989

Tyrosine hydroxylase and levodopa responsive dystonia.

It has been suggested that a form of inherited dystonia responsive to levodopa might be due to an abnormality of tyrosine hydroxylase gene. This hypothesis has been tested using a cDNA tyrosine hydroxylase gene probe in three families with this disorder. No evidence for genetic linkage between the disease and tyrosine hydroxylase loci was found; it is possible that the disorder results from a post-transcriptional defect confined to the brain.

Chromosome Mapping↗
PubMed1988

Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies.

In vitro studies of muscle mitochondrial metabolism in patients with mitochondrial myopathy have identified a variety of functional defects of the mitochondrial respiratory chain, predominantly affecting complex I (NADH-CoQ reductase) or complex III (ubiquinol-cytochrome c reductase) in adult cases. These two enzymes consist of approximately 36 subunits, eight of which are encoded by mitochondrial DNA (mtDNA). The increased incidence of maternal, as opposed to paternal, transmission in familial mitochondrial myopathy suggests that these disorders may be caused by mutations of mtDNA. Multiple restriction endonuclease analysis of leukocyte mtDNA from patients with the disease, and their relatives, showed no differences in cleavage patterns between affected and unaffected individuals in any single maternal line. When muscle mtDNA was studied, nine of 25 patients were found to have two populations of muscle mtDNA, one of which had deletions of up to 7 kilobases in length. These observations demonstrate that mtDNA heteroplasmy can occur in man and that human disease may be associated with defects of the mitochondrial genome.

Adult↗
PubMed1988

Genetic prediction in Huntington's disease: what are the limitations imposed by pedigree structure?

The major factor limiting use of the polymorphic DNA sequence D4S10, genetically linked to the Huntington's disease (HD) locus, in clinical practice is the fragmented nature of HD families. A population survey in South Wales suggested that genetic prediction would only be possible in 15% of adults at risk as a result of this. We have analysed pedigrees from 151 families, containing 482 adults between 18 and 45 years of age who were at high risk of developing HD, 157 of whom had attended genetic counselling clinics. Thirty-seven percent of adults at high risk in these kindreds had the appropriate pedigree structure needed for presymptomatic testing. It should be possible to perform fetal exclusion tests in about 80% of pregnancies at risk.

Adolescent↗
PubMed1988

The diverse neurological features of Niemann-Pick disease type C: a report of two cases.

Two cases of Niemann-Pick disease type C are described in order to illustrate the variable neurological features of this rare condition. One presented with a predominantly akinetic-rigid syndrome at the age of 5 years. The second developed progressive ataxia, accompanied by a vertical gaze palsy, when she was 13. Neither patient had hepatosplenomegaly; the diagnosis of Niemann-Pick disease type C was based on finding foamy storage cells in bone marrow aspirates.

Adolescent↗
PubMed1988

Mitochondrial DNA polymorphism in mitochondrial myopathy.

In order to test the hypothesis that mitochondrial myopathy may be caused by mutation of the mitochondrial (mt) genome, restriction fragment length polymorphism in leucocyte mt DNA has been studied in 38 patients with mitochondrial myopathy, 44 of their unaffected matrilineal relatives, and 35 normal control subjects. Previously unreported mt DNA polymorphisms were identified in both patients and controls. No differences in restriction fragment patterns were observed between affected and unaffected individuals in the same maternal line, and there was no evidence of major deletion of mt DNA in patients. This study provides no positive evidence of mitochondrial inheritance in mitochondrial myopathy, but this has not been excluded.

DNA, Mitochondrial↗
PubMed1988

Mitochondrial myopathy: a genetic study of 71 cases.

Of 71 index cases with histologically defined mitochondrial myopathy, 13 (18%) had relatives who were definitely affected with a similar disorder. Eight familial cases from four families were confined to a single generation. In five families maternal transmission to offspring occurred. There were no instances of paternal transmission, but one patient had an affected cousin in the paternal line. No consistent clinical syndrome or pattern of inheritance emerged for any identified defect of the mitochondrial respiratory chain, localised biochemically in 41 cases. Overall, the recurrence rate was 3% for sibs and 5.5% for offspring of index cases. Review of published reports of familial cases of mitochondrial myopathy suggests that the ratio of maternal to paternal transmission is about 9:1. We conclude that these disorders may be caused by mutations of either nuclear or mitochondrial genes.

Central Nervous System Diseases↗
PubMed1988

Central motor conduction in degenerative ataxic disorders: a magnetic stimulation study.

Central motor conduction to small hand muscles was measured using magnetic stimulation of the motor cortex and electrical stimulation of proximal motor roots in 11 patients with Friedreich's ataxia, 10 patients with early onset cerebellar ataxia with retained tendon reflexes (EOCA) and 13 patients with late onset degenerative cerebellar disease (LOCD). Central motor conduction was abnormal in 91% with Friedreich's ataxia, 70% with EOCA and 38% with LOCD. Central motor conduction abnormalities were not specific to individual disorders but were more severe and were related to disease duration in Friedreich's ataxia and EOCA.

Adult↗
PubMed1988

Leukocyte glutamate dehydrogenase activity in patients with degenerative neurological disorders.

Leukocyte glutamate dehydrogenase (GDH) activity was measured in 39 normal subjects, 32 neurological controls, 66 patients with progressive ataxic disorders, 32 with multiple system atrophy, 40 with Parkinson's disease, eight with Steele-Richardson-Olszewski syndrome, eight with juvenile Parkinsonism and four with the dystonia-Parkinsonism syndrome. GDH activity was reproducible to within 10% in leukocyte pellets stored at -70 degrees C for up to 9 months, and did not vary with sex or age in control subjects. There was marked variation in the relative proportions of heat stable and heat labile forms of GDH between control subjects and on repeated assay in the same subject. Total leukocyte GDH activity was similar in normal subjects and neurological controls. Mean total GDH activity was reduced in all patient groups by between 15 to 29% compared with controls. Fourteen patients had total GDH activity below 50% of the control mean, but low values were not specific for any one disease (five had ataxic disorders, four Parkinson's disease, three multiple system atrophy, one juvenile Parkinsonism, and one dystonia-Parkinsonism). The heat labile fraction of GDH represented about 20% of total activity in control subjects, and 27% in the patients with reduced total GDH activity. Thus low GDH activity was not disease-specific in this study, and the heat-labile GDH fraction was not selectively affected. "Reduced" leucocyte GDH activity in some patients may represent no more than the lower end of a normal distribution.

Adult↗
PubMed1988

Restriction endonuclease analysis of leukocyte mitochondrial DNA in Leber's optic atrophy.

In order to test the hypothesis that Leber's optic atrophy may be caused by mutation of the mitochondrial (mt) genome, restriction fragment length polymorphism in leukocyte mt DNA was studied in 16 patients with Leber's optic atrophy, 28 of their unaffected matrilineal relatives, and 35 normal control subjects. No differences in restriction fragment patterns were observed between affected and unaffected individuals in the same maternal line, and there was no evidence of major deletion of mt DNA in patients. This study provides no positive evidence of mitochondrial inheritance in Leber's optic atrophy but does not exclude it.

Adult↗
PubMed1988

Psychiatric and neurological manifestations in systemic lupus erythematosus.

The frequency and type of psychiatric disease were investigated in 40 patients suffering from systemic lupus erythematosus (SLE) and 27 control subjects with rheumatoid arthritis or inflammatory bowel disease. The psychiatric morbidity at the time of interview was the same in the two groups, but the patients with SLE had experienced more episodes of psychiatric illness in the past, and psychotic symptoms occurred only in this group. Half of the patients with SLE had previous or current evidence of neurological involvement; an association was found between neurological disease and psychotic symptoms in SLE, while anxiety and affective disturbances appeared to be closely related to environmental factors in both patients with SLE and controls. There was no correlation between psychiatric and neurological disease and clinical or laboratory indices of disease activity. Magnetic resonance imaging of the brain was performed in 15 patients with SLE. Abnormalities were more often present in those with neurological disease; no such correlation was found with psychiatric illness.

Adolescent↗
PubMed1987

Variant forms of ataxia telangiectasia.

Two ataxia telangiectasia patients with unusual clinical and cellular features are described. Cultured fibroblasts and PHA stimulated lymphocytes from these two patients showed a smaller increase of radiosensitivity than cells from other A-T patients, as measured by colony forming ability or induced chromosome damage respectively, after exposure to ionising radiation. The response of DNA synthesis to irradiation of these cells was, however, the same as for other A-T patients. Cells from a third patient with some clinical features of A-T but with a very protracted course also showed low levels of radiation induced chromosome damage, but colony forming ability and the response of DNA synthesis after irradiation were no different from cells of normal subjects. There was, however, an increased level of translocations and unstable chromosomal rearrangements in this patient's lymphocytes.

Adolescent↗
PubMed1987

Regeneration following tibial nerve crush in the rabbit: the effect of proximal constriction.

In order to test the regenerative capacity of atrophic axons, a constricting ligature was placed around the proximal tibial nerve of the rabbit, and the nerve crushed at the ankle one week later. Axonal atrophy with altered g ratios was subsequently confirmed in fibres distal to the site of ligature and proximal to the site of crush. In nerves with tight proximal ligatures the reinnervation of plantar muscles and the subsequent recovery of distal motor latency were delayed, indicating impaired regeneration. This result may be relevant to the "double-crush" theory of nerve damage.

Action Potentials↗