Pathogenesis of Leigh's encephalomyelopathy

Tang, Thomas T.; Good, Thomas A.; Dyken, Paul R.; Johnsen, Stanley D.; McCreadie, Samuel R.; Sy, Santiago T.; Lardy, Henry A.; Rudolph, Frederick B.

doi:10.1016/s0022-3476(72)80428-1

Cited by 57 publications

(14 citation statements)

References 9 publications

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“…Several authors, impressed with the frequency of lactic acidosis in LD, have studied the ac tivity of enzymes which convert pyruvate into Kreb's cycle intermediates (4)(5)(6). Others, more impressed with the pathological similarities of Leigh's and Wernicke's diseases, have studied the cerebral metabolism of thiamine by LD brains (7).…”

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Neurochemical Changes in Leigh's Disease

Murphy

1976

Journal of Nutritional Science and Vitaminology, J Nutr Sci Vit

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“…This report will review our in vestigations into both theories. curately determined (4,5) or that the patient may not have had LD (6).…”

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Neurochemical Changes in Leigh's Disease

Murphy

1976

Journal of Nutritional Science and Vitaminology, J Nutr Sci Vit

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“…Two theories on the cause of the disease have been proposed: the first based on the demonstration of a deficiency of pyruvate carboxylase [9] subsequently confirmed by Yoshida et al [18], Delvin et al [6], and Tang et al [17] and the second based on a deficiency of thiamine triphosphate, caused by inhibition of thiamine diphosphate: ATP-phosphotransferase by specific inhibitors circulating in the body fluids of affected patients [3].…”

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The Effect of Thiamine Treatment on the Activity of Pyruvate Dehydrogenase: Relation to the Treatment of Leigh's Encephalomyelopathy

1973

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ExtractRats received intraperitoneal injection of thiamine (125 mg'/kg body wt) for 4 consecutive days. There was less inhibition by ATP (9% ± 2%) of the pyruvate dehydrogenase complex of isolated liver mitochondria from treated rats than in liver mitochondria from control rats (30% ± 8%). The liver mitochondria of the treated animals contained about 25% more thiamine pyrophosphate than the mitochondria of the controls (0.48 ± 0.03 and 0.36 ± 0.01 nmoles/mg mitochondrial protein, respectively) .Roche and Reed have demonstrated inhibition of the phosphorylation of the pyruvate dehydrogenase complex by thiamine pyrophosphate, thereby maintaining pyruvate dehydrogenase in the active form. It is suggested that the therapeutic effect of high doses of thiamine given to patients who suffer from Leigh's disease is, at least in part, due to maintainance of the pyruvate dehydrogenase complex in its active form, thus facilitating the oxidation of pyruvate. Speculation

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“…Abnormal chemical data have included lactic acidemia, pyruvic acidemia and elevated concentrations of plasma alanine. Now, four different mechanisms have been proposed to explain the clinical and biochemical findings in Leigh's diseases; pyruvate carboxylase deficiency (Hommes et al 1968;Tang et al 1972;Grover et al 1972), the presence of inhibitory material of thiamine pyrophosphate-ATP-phosphotransferase found in body fluid (Cooper et al 1969(Cooper et al , 1970) pyruvate decarboxylase deficiency (Farmer et al 1973; Blass et al 1976), and cytochrome c oxidase deficiency (Willems 1977).…”

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confidence: 99%