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

In an ultrastructural study of human liver biopsy specimens we found that peroxisomes are regularly present in normal human hepatocytes. Their relationships with the endoplasmic reticulum observed in other species and in other organs were also demonstrable in this material. Some normal peroxisomes were found to display marginal plates or peripheral crystalline inclusions which were present in pathologic specimens as well. In certain inherited metabolic disorders (Menkes' steely hair disease, analbuminemia) the volume of the individual peroxisomes appeared to be considerably reduced. But most pathologic processes affecting hepatocytes seem to produce any or several of the following: increased volume or numbers per cell, changes of shapes, alterations of the consistency of the matrix, appearance of dense numbers per cell, changes of shapes, alterations of the consistency of the matrix, appearance of dense inclusions, or clustering of peroxisomes in some portions of the cytoplasm. Some of these abnormalities are reversible based on observations in three patients with Wilson's disease treated with D-penicillamine. The mean +/- standard deviation of diameters of peroxisomes in four normal subjects was 0.618 +/- 0.143 mum. Significant reductions or increases in mean diameters of peroxisomes were noted in all but two of the 16 pathologic specimens. There were other morphologic abnormalities present in the remaining two specimens. We conclude that various pathologic processes involving the hepatocytic cytoplasm exert different effects on peroxisomes. Although no specific pattern of morphologic alteration emerged from this exploratory study, a possible involvement of peroxisomes ought to be considered whenever metabolic or pathologic processes affect the liver.
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PMID:The peroxisomes of human hepatocytes. 1239 46

Several primarily inherited disturbances of minerals and trace elements have been discovered within the last 20 years. Secondary disturbances of selenium and zinc induced by dietetic treatment of inborn errors of metabolism and by parenteral nutrition also came to our knowledge recently. Two main types of chronic or primary hypomagnesaemia are known which are caused either by impaired intestinal absorption or by false magnesium handling by the kidneys. In acrodermatitis enteropathica, an autosomal-recessive inherited disease leading to characteristic skin lesions, alopecia and dystrophy, low zinc concentrations of serum, urine and hair are measured. The intestinal absorption of zinc is reduced. In copper metabolism two inherited diseases are known with low serum and usually caerulosplasmin concentrations. In Menkes' steely hair syndrome (trichlpoliodystrophy) an intestinal net malabsorption of copper exists, whereas in Wilson's disease the copper contents of several organs are increased.
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PMID:Primary and secondary disturbances in trace element metabolism connected with genetic metabolic disorders. 91 52

Cultured skin fibroblasts from patients with Menkes disease, an X-linked disorder involving a defect in copper metabolism, were analyzed for copper concentration by means of atomic absorption spectrophotometry. These cultures consistently exhibited elevated copper concentrations (mean = 335.5 ng of copper per mg of protein) when compared to control fibroblast cultures (mean = 59.2 ng of copper per mg of protein). External factors that could influence the copper content of cultures were found not to affect the differences in copper concentration between control and Menkes cells. Furthermore, Menkes cells could be differentiated from cultured fibroblasts of controls, of presumed heterozygotes, and of Wilson's disease patients by copper concentration. These observations led to the conclusion that the increased copper content of cultured Menkes cells was characteristic of Menkes disease, resulting from the expression of the genetic abnormality. This provides a genetic marker, a defect in metal metabolism demonstrated in human fibroblasts, that should prove valuable in both the diagnosis of Menkes disease and in the study of the fundamental defect of this genetic disorder.
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PMID:Menkes disease: a biochemical abnormality in cultured human fibroblasts. 106 Nov 60

Increasing loss of vision caused by peculiar macroscopic and functional retinal changes was the first ophthalmologic manifestation of Wilson's disease in a 22-year-old patient. Neither retinal changes nor great visual impairment has been described thus far in the literature concerning this disease. Likely correlations are discussed with Menkes syndrome, an X-linked inborn error of copper metabolism with onset in early childhood.
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PMID:[Retinal changes in Wilson's disease]. 188 68

There are several known examples of mutations which influence copper homeostasis in humans and animals. Pleiotropic effects are observed when the mutant gene disturbs copper flux. In some cases, the mutation alters the level of a specific copper ligand (enzyme) and the clinical consequences are unique. The two most widely studied genetic maladies in humans are Menkes' and Wilson's diseases. Menkes' disease is an X-linked fatal disorder in which copper accumulates in some organs (intestine and kidney) and is low in others (liver and brain). Wilson's disease is an autosomal recessive disorder in which copper accumulates, if untreated, in liver and subsequently in brain and kidney. Pathophysiological consequences of copper deficiency and toxicity characterize these two disorders. Specific mutations of human cuproenzymes include overproduction of copper-zinc superoxide dismutase in Down's syndrome, absence of tyrosinase in albinism, hereditary mitochondrial myopathy due to reduction in cytochrome c oxidase, and altered lysyl oxidase in X-linked forms of cutis laxa and Ehlers-Danlos syndrome. Mutations altering copper metabolism are also known in animals. Several murine mutants have been studied. The most extensively investigated mutants are the mottled mice, in particular brindled mice, which have a mutation analogous to that of Menkes' disease. Another recently described murine mutation is toxic milk (tx) an autosomal recessive disorder that is characterized by copper accumulation in liver. Two other mutants, crinkled and quaking, were once thought to exhibit abnormal copper metabolism. Recent data has not confirmed this. A mutation in Bedlington terriers has been described which is very similar to Wilson's disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Genetic diseases of copper metabolism. 351 56

Several mutations affecting the transport of copper and zinc in humans and in mice have been discovered over the last 15 years, joining the long known disturbance of copper transport in Wilson's disease. Menkes' disease (classical and mild variant forms) and X linked Ehlers-Danlos syndrome (type IX, X linked cutis laxa) have features in common with one another and with the brindled (Mobr) and blotchy (Moblo) mouse mutants, respectively. There may be one allelic series of mutants in each species or two loci may be involved in each. The toxic milk mutant (tx) in the mouse may be homologous to Wilson's disease in man. The defect of intestinal absorption of zinc in acrodermatitis enteropathica has no homologue yet in the mouse. However, the lethal milk (lm) mutant in the mouse may be homologous to a condition of zinc deficiency described in a few breastfed, low birth weight infants. Many more genetic defects of transport of copper and of zinc may await discovery. Conversely, these mutants are valuable in elucidating the normal processes of copper and zinc transport.
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PMID:Of mice and men, metals and mutations. 351 72

Genetic disorders of trace element transport are now known in humans, mice, dogs and cattle. Those involving copper have been known longest and are best known clinically. Effects due to copper deficiency are seen in Menkes' disease, in X-linked cutis laxa and in the X-linked series of mottled mutants in the mouse. Copper accumulation is also harmful, causing damage initially to the liver and later to the kidneys and brain in Wilson's disease, in some Bedlington terriers and in toxic milk mice. Zinc deficiency is seen in acrodermatitis enteropathica and in premature babies born to women who seem to secrete milk that is zinc-deficient, as is seen in lethal milk mice. Study of animal mutants, especially mutant mice, is helpful in understanding the human diseases and identification of the basic defects in trace element transport in these diseases is improving knowledge relevant to trace element nutrition.
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PMID:Inborn errors of trace element metabolism. 390 81

Cultured fibroblasts from Menkes kinky hair disease patients showed markedly reduced succinate dehydrogenase and amine oxidase activities. Cytochrome oxidase activity, however, was greatly reduced in some cells and almost normal in others. Cultured fibroblasts from patients with Wilson's disease showed moderately reduced succinate dehydrogenase and cytochrome oxidase activities. Amine oxidase activity was only slightly reduced when compared to that of normal. These results indicated that the histochemical phenotype observed in fibroblasts from patients with Menkes kinky hair disease and Wilson's disease were distinctly different from each other and from normal fibroblasts.
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PMID:Histochemical studies of fibroblasts from patients with Menkes kinky hair disease and Wilson's disease. 629 Apr 31

Copper concentration, intracellular copper distribution, and inducibility of metallothionein-like metal-binding protein (MLP) by copper or cadmium addition to culture medium were compared among three types of skin fibroblasts derived from patients with Menkes' disease and Wilson's disease, both exhibiting genetic defects of copper metabolism, and from normal subjects (control). Skin fibroblasts were cultivated in Dulbecco's modified Eagle's medium supplemented with 10% fetal calf serum and antibiotics in 5% CO2 at 37 degrees C. Cells were harvested with rubber-policeman, washed twice with phosphate-buffered saline, pH 7.2, suspended in deionized water, and homogenized. The homogenate from each cell type was used to determine the concentration of copper by atomic absorption spectrophotometry employing graphite-rod atomizer after lyophilization, ashing in HNO3, and coprecipitation with zirconium. Intracellular copper concentration was elevated in Menkes' cells (420 ng Cu/mg of protein) and Wilson's cells (217 ng Cu/mg of protein) than in control cells (90.0 ng Cu/mg of protein), although one of four Wilson's strains showed normal copper level (70.5 ng Cu/mg of protein). Cytosol copper concentration was 5.8-fold higher in Menkes' cells but only 1.3-fold in Wilson's cells than in control cells, and cytosol copper accounted for only 35% of total intracellular copper in Wilson's cells as compared with 68% and 52% in Menkes' and control cells, respectively. These suggest that accumulated copper in each cell type is differently distributed within cells; in Menkes' cells exclusively into cytosol, but in Wilson's cells into particulates rather than cytosol. Elution profiles from Sephadex G-75 columns indicated that most of copper had bound to MLP in Menkes' cells, though no Cu-MLP was detectable in Wilson's or control cells under these experimental conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Copper level and metallothionein-like Cu-binding protein in cultured skin fibroblasts from patients with Menkes' disease and Wilson's disease]. 652 19

A method is reported for isolation and purification of human ceruloplasmin and apoceruloplasmin from serum. It involves a rapid and mild procedure by ion exchange chromatography on DEAE-Sephacel using a pH and ionic strength concave gradient. It was applied to serum of patients with oculocutaneous albinism, Wilson's disease, Menkes' disease and pregnant women. The ceruloplasmin obtained by this method is undegraded, and homogeneous by physico-chemical and immunochemical analysis.
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PMID:Isolation and purification of ceruloplasmin in oculocutaneous albinism, Menkes' disease, Wilson's disease and pregnant women. 661 79


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