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Biomedical subjects

J B Clark

Publications and source records attributed to J B Clark.

At least 145 records · Page 8Linked to original sources
PubMed1990

The molecular pathology of respiratory-chain dysfunction in human mitochondrial myopathies.

Some of the different molecular pathologies of respiratory-chain dysfunction in human mitochondrial myopathies will be reviewed in relation to the findings in 58 cases. Deletions of mitochondrial DNA were identified in 21 cases [36%]. There was some correlation between the sites of the deletion and the mitochondrial biochemistry in patients with defects of Complex I but not in cases with more extensive loss of respiratory chain activity. Complex I and Complex IV polypeptides were usually normal in deleted cases. Non-deleted cases, however, often showed specific subunit deficiencies which involved the products of both nuclear and mitochondrial genes. Immunoblots of respiratory-chain polypeptides in one case pointed to defective translocation of the Rieske precursor from the cytosol into the mitochondria. The pathogenic role of circulating autoantibodies to specific matrix proteins and the nature of the target antigens in two patients with mitochondrial encephalomyopathies and respiratory-chain dysfunction will also be discussed.

Autoantibodies↗
PubMed1990

Epizootiology of neoplasms in bony fish of North America.

Over the past 25 years, there have been an increasing number of fish tumor epizootics recognized in discrete geographical areas in North America. This is consistent with an association between tumor development in fish and exposure to waterborne contaminants as a result of increased industrialization. Reports of fish tumor epizootics from the literature, plus acquisitions at the Registry of Tumors in Lower Animals, Smithsonian Institution originate from 41 geographical regions in North America. Epizootics of hemic, neural, connective tissue, and gonial neoplasms seem unrelated to environmental pollution, but epizootics of hepatic and epidermal neoplasms appear to be caused or strongly influenced by environmental pollution. The 14 species with epizootic liver tumors are all bottom feeding fish, and tumor-bearing fish are generally located in areas where chemical contaminants are concentrated. Epidermal neoplasms are also found in fish near polluted areas, but a direct cause-and-effect link with chemical carcinogens is not clear.

Animals↗
PubMed1990

A mitochondrial encephalomyopathy with specific deficiencies of two respiratory chain polypeptides and a circulating autoantibody to a mitochondrial matrix protein.

A 15-yr-old boy with mitochondrial encephalomyopathy and NADH CoQ reductase (Complex I) deficiency is presented. Immunoblotting demonstrated specific deficiencies of the 24 kDa FeS protein of Complex I and subunit II of Complex IV. The patient's serum contained an antibody to a specific mitochondrial matrix polypeptide of apparent Mr 41 kDa. The specific polypeptide deficiencies involve products of nuclear (24 kDa FeS protein) and mitochondrial (subunit II) genes and suggest some intergenomic regulation. The relevance of the circulating antibody to the pathogenesis of the patient's Complex I deficiency is discussed.

Adolescent↗
PubMed1990

Mitochondrial complex I deficiency in Parkinson's disease.

The structure and function of mitochondrial respiratory-chain enzyme proteins were studied postmortem in the substantia nigra of nine patients with Parkinson's disease and nine matched controls. Total protein and mitochondrial mass were similar in the two groups. NADH-ubiquinone reductase (Complex I) and NADH cytochrome c reductase activities were significantly reduced, whereas succinate cytochrome c reductase activity was normal. These results indicated a specific defect of Complex I activity in the substantia nigra of patients with Parkinson's disease. This biochemical defect is the same as that produced in animal models of parkinsonism by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and adds further support to the proposition that Parkinson's disease may be due to an environmental toxin with action(s) similar to those of MPTP.

Electron Transport Complex II↗
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↗
PubMed1990

Involvement of lactic acidosis in anoxia-induced perturbations of synaptosomal function.

L-Lactate (4-32 mM) added exogenously to resting or depolarised rat forebrain synaptosomes led to a significant decrease in intrasynaptosomal pH. Similarly depolarisation-induced increases in intrasynaptosomal calcium, calcium uptake, and acetylcholine release were all inhibited. These effects mimicked those previously observed in synaptosomes under anoxic conditions and suggest that lactate may be involved in limiting the damage due to calcium accumulation occurring during ischaemia. D-Lactate (added exogenously up to 32 mM) did not produce similar effects on these parameters even though the concentrations of intrasynaptosomal D-lactate reached levels comparable to those obtained with L-lactate (at 8-16 mM exogenous concentration). The results suggest that the mechanism of action of lactate on these parameters is stereospecific for the L-enantiomer. The effect of glucose availability on lactate production was assessed to explore the role of substrate availability on ischaemia/anoxic events. When exogenous glucose was increased (10-60 mM), there was no further increase in lactate production in normoxic synaptosomes, which suggests that glucose is not limiting under these conditions. When glucose was removed, as may occur in complete ischaemia, there was a significant decrease in lactate production after 60 min under anoxic or normoxic conditions. It would seem likely therefore that the mechanism underlying the changes observed in synaptosomes incubated under conditions reflecting complete ischaemia does not involve lactate.

Acidosis, Lactic↗
PubMed1990

Policy considerations of human immunodeficiency virus (HIV) infection in U.S. Naval aviation personnel.

This article reviews the available medical data that form the basis for the U.S. Navy's policy on aeromedical disposition of Human Immunodeficiency Virus (HIV) seropositive flyers. Following a brief review of military HIV antibody testing and clinical evaluation, this article addresses the main issue in the Navy's aeromedical disposition policy--the subtle neurologic sequelae of HIV infection or HIV encephalopathy. Following a review of the available knowledge of HIV involvement in the nervous system, the aeromedical considerations that form the basis of Navy policy of permanently grounding without waiver all HIV seropositive flyers is discussed.

AIDS Dementia Complex↗
PubMed1990

Cervical dystonia following exposure to high-G forces.

Injuries to the cervical region have been associated with high-G loads sustained during air combat maneuvering (ACM) in high performance fighter aircraft. The spectrum of injuries ranges from mild neck pain to musculoskeletal strain, injury to the nerve roots or spinal cord, and fracture of the cervical spine. A 36-year-old fighter pilot with 2,800 h in tactical jet aircraft developed progressive cervical dystonia (spasmodic torticollis), following an ACM flight. The patient was successfully treated with local intramuscular injections of botulinum toxin into the affected cervical muscles, resulting in total relief of his spasmodic torticollis. The aeromedical considerations of this rare complication of exposure to G forces in high performance aircraft are discussed.

Adult↗
PubMed1990

Navy helicopter pilot with a juxtasellar mass: case report with aeromedical considerations.

A Navy helicopter pilot was found to have a suprasellar mass during evaluation for primary infertility and mildly elevated prolactin level. Extensive evaluation revealed no other abnormalities. After 1 year of followup without radiographic tumor enlargement, he was returned to flying duties with continuing medical monitoring. Aeromedical considerations for tumors in the juxtasellar region are reviewed, including neuroendocrine disorders, neuro-ophthalmologic defects, and neurological impairment. The impact of improved diagnostic capabilities on aeromedical disposition is discussed.

Adult↗
PubMed1989

An unusual case of carnitine palmitoyl transferase deficiency.

A 36-year-old man presented with episodic exertional dyspnea, fluctuating exercise intolerance, and myoglobinuria. He never experienced cramps or myalgias. Subsequent evaluation revealed carnitine palmitoyl transferase deficiency. The unusual features of this case suggested that carnitine palmitoyl transferase deficiency may have a more diverse clinical picture than previously described.

Acyltransferases↗