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Query: UMLS:C0022716 (Menkes)
 1,057 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Menkes' disease is an inherited disturbance of copper metabolism. Addition of copper to the medium of cultured fibroblasts and lymphoblasts from patients with Menkes' disease results in an increased induction of metallothionein. We investigated the metallothionein induction in response to copper and zinc in muscle cells (myoblasts and myotubes). Metallothionein synthesis was analyzed by gel electrophoresis of labeled proteins and metallothionein synthesis in muscle cells was compared with the synthesis in fibroblasts. The induction by copper was higher both in muscle cells and in fibroblasts from the Menkes' patient compared to the control cells. Hybrid myotubes obtained by fusion of control myoblasts and Menkes' myoblasts render a system in which complementation can be studied. Metallothionein synthesis in hybrid myotubes occurred at a level intermediate between the synthesis in Menkes' and control myotubes. The abnormal accumulation of copper-induced metallothionein was only partially corrected by fusion with normal cells. Metallothionein induction by zinc was similar in Menkes' and control fibroblasts. Combination of copper and zinc yielded no differences in additional metallothionein synthesis for Menkes' cells and control fibroblasts. Therefore, metallothionein induction in Menkes' disease can primarily be accounted for by copper rather than by zinc.
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PMID:Metallothionein in Menkes' disease: induction in cultured muscle cells. 208 40

We present 64Cu uptake studies in cultured muscle cells from a one-year-old patient with Menkes' disease. The cultured muscle cells from the patient showed a five-fold higher 64Cu uptake than control muscle cells. Copper uptake in muscle cells was of the same magnitude as that found in fibroblasts from the patient and also from other Menkes' patients. The copper content of a muscle biopsy from the patient was twice that of a control biopsy. The enhanced uptake is probably copper specific, since zinc uptake was unaltered in both muscle cells and fibroblasts from the patient. Cytochrome c oxidase in the muscle of the patient was reduced to one-third of the value for controls, which is in agreement with the hypothesis that in Menkes' disease copper accumulates in a biologically non-active form. However, in cultured muscle cells and fibroblasts from the patient the cytochrome c oxidase activity was in the normal range, probably because of the relatively large amount of copper already available in the culture medium.
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PMID:Muscle cell cultures in Menkes' disease: copper accumulation in myotubes. 216 83

Neuropathological and enzyme-histochemical studies were performed on brindled mouse hemizygotes (BMs) and normal littermates at the age of 2 days, 7 days, 11 days and 14 days, together with an investigation of their tissue copper levels. A greatly increased copper concentration was confirmed in the kidney and intestine and a greatly reduced concentration in the liver and brain of BMs. The copper concentration in the brain increased gradually with age in the normal littermates, whereas this did not occur in BMs. There was no significant difference in the tissue copper concentration between the cerebrum and the cerebellum-brainstem in BMs or in normal littermates. Light and electron microscopy of the BM brain revealed progressive neuronal degeneration in association with increased mitochondrial changes (ballooning and crista disintegration). Enzyme histochemical examinations demonstrated a progressive comparative decrease (i.e., an increased difference from normal) of cytochrome oxidase activity in the BM brain. These data suggest that progressive degeneration of the brain in Menkes' disease is attributable to mitochondrial degeneration caused by a comparative decrease of both copper concentration and cytochrome oxidase activity in the brain.
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PMID:Chronological observations of histological changes, cytochrome oxidase activity and copper level in the brain of the postnatal brindled mouse. 216 17

As a possible preventive measure for brain dysfunction in Menkes disease, prenatal treatment by maternal administration of zinc, vitamin E and copper was examined in brindled mutant mice. During pregnancy and lactation, female heterozygous mice received 20 ppm zinc or 0.004% alpha-tocopherol acetate (vitamin E) throughout and 6 ppm copper from gestational day 13 in the drinking fluid, ad libitum. The maternal administration of zinc and vitamin E, as antioxidants, or copper resulted in decreased fetal and neonatal death of offspring, especially those of hemizygous males, as compared with the administration of water only. When offspring did not grow, maternal abnormal movements, which comprised rotatory movements of high speed with tremor and ataxia, were frequently observed. In the heterozygotes with abnormal movements, the level of lipid peroxidation in cerebrum and the concentration of copper in kidney were much higher than those in the heterozygotes with normal movement. Morphologically, in cerebellum of the heterozygotes with abnormal movements, the loss of Purkinje cells, abundance of lipofuscin granules and abnormal mitochondria or degenerative bodies of high electron density were frequently observed, as compared with heterozygotes with normal movement. These findings suggest that the development of hemizygous male mice may be influenced by both copper and oxygen radical metabolism.
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PMID:Abnormal movements in brindled mutant mouse heterozygotes: as related to the development of their offspring--biochemical and morphological studies. 216 11

Brain mitochondrial enzyme activities were examined in 15-day-old suckling mice which were daily injected with D-penicillamine (DP), a chelating agent of copper. Newborn mice treated with DP (1 g/kg/day) showed retarded weight gain, hyperelasticity of skin, and a bizarre forelimb posture with subcutaneous edema on experimental day (ED) 7. Paraparesis or dragging of the hindlimbs was observed by ED 15. Brain copper contents of DP-treated mice decreased to 34% of the controls of ED 15. Cytochrome c oxidase activity (complex IV) in the brain showed 51% decrease of the controls, on the contrary, rotenone-sensitive NADH cytochrome c reductase (complex I + III) and succinate cytochrome c reductase (complex II + III) were normal. Histochemistry of cytochrome c oxidase in the cerebellum of DP-treated mice disclosed diffuse reduction of staining, especially in Purkinje cells. These data show that DP-induced copper deficiency in the brain subsequently disturbs mitochondrial electron transport system, selectively cytochrome c oxidase activity. This seems to be a useful animal model not only for Menkes' kinky hair disease but also for mitochondrial encephalomyopathy.
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PMID:D-penicillamine-induced copper deficiency in suckling mice: neurological abnormalities and brain mitochondrial enzyme activities. 217 57

The wet weight, copper content, mitochondrial electron-transfer complexes and 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNPase) were measured in various organs including brain, liver, kidney, and heart in macular mutant mice which are considered to be an appropriate model for human Menkes kinky hair disease (MKHD). Copper contents were decreased markedly in liver, brain, and heart. However a significant increase was noted in kidney, suggesting a disproportionate distribution of copper contents in each organ in this mutant mouse. Regarding mitochondrial electron-transfer complexes, only cytochrome c oxidase, a copper dependent enzyme, was found to be decreased in heart and brain. This alteration in the brain was already demonstrated at 2 days. CNPase was not decreased in its activity at 7 days, but decreased at 14 days, supporting progressive demyelination. These results suggested that this mutant mouse would be a useful animal model for clarifying the pathogenesis in human MKHD.
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PMID:[A pathophysiological study of macular mutant mouse as a model of human Menkes kinky hair disease. I. Copper contents and copper dependent enzyme activities in various organs]. 217 32

Menkes' kinky hair disease (trichopoliodystrophy) is a rare inherited X-linked recessive disease with an incidence of about 1:35,000, and is rare reported previously in Taiwan. We present 2 cases with typical features including sparse, coarse and stubby, kinky hair, depigmented skin, pudgy face, arrow-shaped upper lip, hypotonia, Babinski signs bilaterally, profound psychomotor retardation with disability of head control or rolling over, and poorly controlled myoclonic jerks. Both were male infants with a family history of male relatives died in early childhood. Their hairs showed pili torti and trichorrhexis nodosa microscopically. Serum levels of copper were 14 ug/dl and 20 ug/dl. Ceruloplasmin levels were 10.4 mg/dl and less than 7 mg/dl. Their EEG showed abnormal generalized brain polyspike waves. Brain CT scan showed generalized brain atrophy, and chronic subdural hematoma in case 1. Bilateral urinary bladder diverticula and spurs over the distal ends of the femoral diaphysis were found in case 1. Normal urinary bladder was found in case 2 initially, then diverticula developed one year later. They are currently on anticonvulsants (Rivotril) therapy. Repeated attacks of respiratory infection, myoclonic seizure, hypotonia, and static neurologic developmental status are noted.
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PMID:[Menkes' kinky hair disease: report of 2 cases]. 217 69

The patient developed myoclonic seizures at 3 months of age and his hair demonstrated the pili torti pattern. The low serum copper content and ceruloplasmin confirmed the diagnosis of Menkes disease. The characteristic signs on the images were: high echo level regions in the cerebrum as detected by brain ultrasonography, low density areas of white matter detected by CT scan, and low signal intensities of white matter by both T1 and balanced MR images.
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PMID:Serial imaging of Menkes disease. 218 34

The macular mouse is a mutant mouse with a defect in copper transport and an X-linked recessive inheritance. Its hemizygote (Ml/y) is considered to be an appropriate model fo Menkes kinky hair disease (MKHD). In this study, homozygote (Ml/Ml) were bred by coupling CuCl2-treated Ml/y with heterozygote (Ml/+). Both Ml/Ml and Ml/y die around day 15 of age. However, treatment with CuCl2 enables them to live until adulthood. The brains of Ml/Ml were chronologically examined by light and electron microscopy. In the non-treated Ml/Ml, abnormal mitochondria increased in number in the cerebral cortical neurons and in the cerebellar Purkinje cells from day 7 to 14 of age. In the treated Ml/Ml, the administration of CuCl2 improved the abnormality of the mitochondria in the cerebrum by day 20, but those in the Purkinje cells remained until day 60. Flattened cisterns and intracytoplasmic inclusions were also observed in the Purkinje cells of treated Ml/Ml. These ultrastructural changes were quite similar to those observed in the Ml/y. Our mutant mice (treated Ml/Ml), when they are coupled with treated Ml/y, can give birth to offspring, all of which will be genetically Ml/y or Ml/Ml. These fetal mice will be very helpful for studying the pathological and biochemical condition of prenatal MKHD.
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PMID:Electron microscopic study on the homozygote (Ml/Ml) of the macular mutant mouse. 228 83

Fibroblasts from the brindled mouse model of Menkes disease are known to accumulate excess copper. Most of the copper in the cytosol of these fibroblasts is bound to metallothionein (MT), which is elevated in Menkes or brindled mouse fibroblasts. Copper accumulation by normal fibroblasts containing excess MT was examined to determine if the excess copper accumulation phenotype was secondary to excess MT or associated with the primary defect in fibroblasts from the brindled mice. MT was induced in normal fibroblasts by copper, zinc or dexamethasone to levels comparable with those in brindled mice fibroblasts, as determined by radioimmunoassays. Normal fibroblasts containing excess MT accumulate copper normally, i.e. they do not exhibit the excess copper accumulation phenotype. Consistent with this result, copper efflux from normal fibroblasts containing excess MT was also normal. The data suggest that one function of the protein associated with the primary defect is to help determine how much copper is taken up and retained by fibroblasts and other cell types exhibiting the excess copper phenotype in Menkes disease. The capacity of this protein is apparently exceeded in normal fibroblasts if serum or albumin is not present extracellularly to limit total copper uptake. Consistent with a defect in an intracellular protein, the kinetics of copper transport by brindled mice fibroblasts were found to be normal.
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PMID:The relationship of excess copper accumulation by fibroblasts from the brindled mouse model of Menkes disease to the primary defect. 233 1


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