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Biomedical subjects

V M Mann

Publications and source records attributed to V M Mann.

11 recordsLinked to original sources
PubMed1992

Human mitochondrial complex I dysfunction.

In humans, complex I dysfunction has been observed in a high percentage of patients with mitochondrial myopathy. Analysis of mitochondria from these patients suggests the function and assembly of complex I is particularly susceptible to abnormalities of mitochondrial DNA, involving either point mutations of tRNA genes or major deletions. The evidence for a complex I defect in Parkinson's disease is accumulating, although the cause of this deficiency or the role it plays in the events that culminate in dopaminergic cell death remains unresolved.

Aging↗
PubMed1992

Quantitation of a mitochondrial DNA deletion in Parkinson's disease.

A 5 kilobase deletion in mitochondrial DNA (mtDNA) has been reported to be responsible for the specific complex I deficiency in the substantia nigra (SN) of the Parkinson's disease (PD) brain. We have studied mitochondrial respiratory chain function in the SN from control and PD subjects, and analysed mtDNA, extracted from the same tissues, by Southern blot and the polymerase chain reaction (PCR). Quantitation of the levels of the deletion indicate that it does not contribute to the pathogenesis of PD nor to a complex I deficiency but seems likely to be an age-related observation.

Blotting, Southern↗
PubMed1992

Mitochondrial function in Parkinson's disease. The Royal Kings and Queens Parkinson's Disease Research Group.

There is increasing evidence for a defect of mitochondrial respiratory chain function in Parkinson's disease. Specific NADH CoQ1 reductase (complex I) deficiency has been identified in the substantia nigra. Available evidence suggests that this defect is confined to the substantia nigra and is not present elsewhere in the parkinsonian brain. The absence of a detectable mitochondrial abnormality in the substantia nigra of patients with multiple system atrophy also suggests that the complex I deficiency in Parkinson's disease is not simply due to an artifact of neuronal degeneration. Evidence for abnormal mitochondrial function in skeletal muscle is conflicting; two studies showed multiple respiratory chain defects and one study was unable to demonstrate any deficiency. A severe deficiency of complex I activity has been found in platelet mitochondria from parkinsonian patients. This finding has not as yet been confirmed. Platelet homogenates do not show the complex I deficiency, however, suggesting that such a preparation may be too insensitive to detect the defect. The role of complex I deficiency in the events that culminate in dopaminergic cell death in Parkinson's disease remains unresolved. It is likely that if this mitochondrial defect is confirmed, it will be related to a number of other factors, including environmental agents, oxidative stress, and genetic predisposition.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1992

Analyses of mitochondrial respiratory chain function and mitochondrial DNA deletion in human skeletal muscle: effect of ageing.

The analysis of human skeletal muscle mitochondria revealed a progressive decline in mitochondrial respiratory chain function with age. The activities affected to the greatest extent were those of complexes I and IV which were decreased by 59% and 47% respectively between the ages of 20-30 years and 60-90 years of age. Quantitation of the 5 kb 'common' deletion of mtDNA using PCR revealed a progressive accumulation with age, from approximately 1 in 100,000 at 21 years to 1 in 10,000 at 56 years and 1 in 5000 at 78 years of age. The low absolute levels of this mutation are unlikely to contribute significantly to the observed mitochondrial dysfunction.

Adult↗
PubMed1992

Subcellular fractionation evidence for a putative peroxisome-mitochondrion attachment in the liver of normal and genetically obese (ob/ob and db/db) mice.

1. Liver post-nuclear supernatants (PNS) from several mouse strains were fractionated by zonal centrifugation and fractions analysed by marker-enzyme estimations+electron microscopy. 2. Rate-dependent banding of PNS yielded peroxisome-enriched (PER) and mitochondrion-enriched (MER) regions. 3. Density-dependent banding of PER yielded peroxisomes (approximately 1.22 g/ml) well separated from mitochondria (approximately 1.8 g/ml). 4. Density-dependent banding of MER yielded peroxisomes that co-distributed with mitochondria and electron microscopy revealed close proximity of the two organelles. 5. Experiments demonstrated that co-distribution was not due to weak binding of proteins or to agglutination of organelles. 6. The results indicate in vivo attachment of some mitochondria and peroxisomes.

Animals↗
PubMed1992

Association of monoamine oxidase and malate dehydrogenase with liver peroxisomes of genetically obese (ob/ob and db/db) mice.

1. Liver post-nuclear supernatants (PNS) from genetically obese (ob/ob and db/db), lean (+/?), and albino mice were fractionated by dual centrifugation in B-XIV zonal rotors and subcellular fractions were analysed by marker-enzyme estimations and by electron microscopy. 2. Rate-dependent banding of PNS yielded a peroxisome-enriched region (PER) well-separated from mitochondria. 3. Density-dependent banding of PER in ob/ob and db/db mice only, yielded purified peroxisomes which were associated with malate dehydrogenase (cytosolic) and monoamine oxidase. 4. Markers for the mitochondrial matrix, intermembrane space and inner membrane compartments were absent from the peroxisomes. 5. The experimental results are interpreted as indicating that peroxisomes of genetically obese mice are either altered so that protein import is imprecise or so that their attachment to mitochondria is more extensive.

Animals↗
PubMed1992

Brain, skeletal muscle and platelet homogenate mitochondrial function in Parkinson's disease.

The recent discovery of mitochondrial complex I deficiency in the substantia nigra of patients with idiopathic Parkinson's disease has provided new understanding into the possible mechanisms that may underlie this neurodegenerative disorder. The biochemical defect is identical to that induced in humans, primates and mice exposed to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. We have studied mitochondrial respiratory chain function in various brain regions, in skeletal muscle and in blood platelets from patients with idiopathic Parkinson's disease and from matched controls. We provide evidence suggesting that the complex I deficiency in Parkinson's disease is limited to the brain and that this defect is specific for the substantia nigra. The tissue specificity of the complex I deficiency in Parkinson's disease and its localization to the substantia nigra support the proposition that complex I deficiency may be directly involved in the cause of dopaminergic cell death in Parkinson's disease. An understanding of the molecular basis of this biochemical defect will provide valuable insight into the cause of Parkinson's disease. Our findings of normal mitochondrial function in platelet homogenates suggests that this tissue cannot be used to develop a 'diagnostic test' for Parkinson's disease.

Aged↗
PubMed1990

Occurrence of IgA and IgG antibodies to select peptides representing human papillomavirus type 16 among cervical cancer cases and controls.

We used an enzyme-linked immunosorbent assay to test sera from 186 cases of invasive cervical cancer and 172 age-matched controls for IgG and IgA antibodies to an human papillomavirus 16 E7 peptide and to peptide 245, representing an epitope in E2. Cases had significantly higher mean absorbance values than controls for both immunoglobulin isotypes to E7 and elevated mean values for IgG to peptide 245. Since absorbances were not normally distributed we analyzed cervical cancer risk for seropositive and seronegative women. Of the traditional cervical cancer risk factors, cigarette smoking, educational level, number of pregnancies, time interval since last Papanicolaou smear, and age at first intercourse influenced the distribution of seropositivity to some of the viral antigens. Adjusting for these variables, the odds ratios of cervical cancer associated with IgG to E7 was 5.28 [95% confidence (95% CI) = 2.4-11.6] and that with IgA to E7 was 2.67 (95% CI = 1.3-5.3). IgG to peptide 245 was less strongly associated, odds ratio 1.68 (95% CI = 1.2-3.3), and IgA to peptide 245 was not significantly associated with disease. These findings suggest that antibodies to E7 are markers for invasive cervical cancer. However, seropositivity correlated poorly with clinical state, survival, or the presence of human papillomavirus DNA in the cancer tissue.

Antibodies, Viral↗
PubMed1990

Anatomic and disease specificity of NADH CoQ1 reductase (complex I) deficiency in Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is thought to produce parkinsonism in humans and other primates through its inhibition of complex I. The recent discovery of mitochondrial complex I deficiency in the substantia nigra of patients with Parkinson's disease has provided a remarkable link between the idiopathic disease and the action of the neurotoxin MPTP. This article shows that complex I deficiency in Parkinson's disease is anatomically specific for the substantia nigra, and is not present in another neurodegenerative disorder involving the substantia nigra. Evidence is also provided to show that there is no correlation between L-3,4-dihydroxyphenylalanine therapy and complex I deficiency. These results suggest that complex I deficiency may be the underlying cause of dopaminergic cell death in Parkinson's disease.

Citrate (si)-Synthase↗