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

The copper content of various organs of ;brindled' female heterozygotes and male mice affected by this X-linked mutation are documented at the last day of intrauterine development, at 1 day after birth and at 11 days of age. The findings indicate defective placental transfer of copper in utero, and an even more marked defect in intestinal absorption of copper after birth. In addition there is an abnormal distribution of copper among the tissues of the body once it is absorbed. The mutation produces abnormal accumulation of copper in kidney, in gut mucosa and in testis, whereas liver, brain, plasma and most other organs show diminished copper concentrations. The intestinal malabsorption of copper is accompanied by accumulation of abnormal amounts of the metal in the intestinal-mucosa cells. Copper concentrations in both mucosa and luminal contents rise progressively from duodenum to ileum. Defective upper-intestinal absorption, consequent progressive increase in luminal copper concentration and pinocytosis in the ileum would seem to explain the findings. Radioisotopic studies eliminated the possibility of excessive excretion of copper in bile or across the intestinal mucosa. Detailed comparison with findings in humans with Menkes' syndrome is difficult because of the different stages of development at which the studies have been performed, but the results seem in general to conform very satisfactorily. Those differences seen are probably explicable by known species differences. All the findings are in accord with a hypothesis that the basic defect involves accumulation and retention of copper in the cells of affected tissues such as kidney, gut mucosa and placenta.
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PMID:Copper metabolism in mottled mouse mutants: copper concentrations in tissues during development. 57 17

Fibroblasts from infants with Menkes kinky hair syndrome, which accumulate excessive quantities of copper, are thought to represent a disorder of copper storage or transport. Because of this abnormality, it was thought that they might provide a useful system for investigation of the presumed storage or transport protein metallothionein. Data are presented which are consistent with defective copper efflux from the mutant cells. Because of the more specific role of metallothionein in cadmium detoxification, studies of cadmium metabolism were undertaken which demonstrated abnormal cadmium retention and metallothionein induction in the mutant cells. The association, therefore, of a defect of cadmium metabolism and storage with an abnormality of copper efflux provides evidence implicating metallothionein in copper transport for fibroblasts.
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PMID:Role of metallothioneins in copper transport in patients with Menkes syndrome. 68 47

Two species of metallothioneins were isolated from both normal and Menkes kinky hair disease (MKHD) patient livers. Atomic absorption determination of metals indicated that the patient liver metallothioneins had lower copper and cadmium content than normals. Isotope exchange studies, carried out by incubating native metallothioneins with copper-64 or cadmium-109 demonstrated a decreased affinity for copper and an increased affinity for cadmium in both MKHD metallothioneins. An hypothesis is proposed in which metallothionein functions as an intracellular copper carrier and is responsible for the transport of copper between the cells and the surrounding. Change in the copper affinity of the metallothioneins was suggested to be the major abnormality in MKHD.
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PMID:Metal-binding studies of metallothioneins in Menkes kinky hair disease. 69 18

The dose response as well as kinetics of uptake and retention of copper and cadmium of normal and Menkes kinky hair disease (MKHD) cultured fibroblasts are described. In basal culture medium, intracellular copper concentration in MKHD fibroblasts was approximately 3 times that of control cultures. The intracellular copper concentration of MKHD cells was significantly higher than that of normal fibroblasts at medium copper concentrations below 20 microgram/ml. Death of MKHD cells occurred at medium copper concentrations between 15 and 20 microgram/ml with an intracellular copper level 3 times that at basal medium. Normal cells died at medium copper concentration above 30 microgram/ml with an intracellular copper concentration 19 times that at basal medium. These observations suggested the existence of a regulatory mechanism for maintenance and control of intracellular copper in normal fibroblasts which is effective at medium copper concentrations below 30 microgram/ml. This system is defective in MKHD fibroblasts. In basal medium MKHD and normal fibroblasts had similar intracellular cadmium concentrations; however, at higher medium cadmium concentrations MKHD cells had increased intracellular cadmium levels. The uptake of both 64Cu and 109Cd was significantly higher in MKHD cells than in normal cells, indicating that the uptake of 64Cu and 109Cd is not impaired in MKHD cells. A higher retention of 64Cu was observed in MKHD cells at both 37 degrees C and 4 degrees C. No obvious trend, however, was observed in the difference of retention of 109Cd between MKHD and normal cells. An impairment of egress of copper in MKHD cells is implicated by these results.
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PMID:Cell culture studies of Menkes kinky hair disease. 69 39

The authors report the sixth case of Menkes' kinky hair disease. This boy has been observed for as long as 16 months, and he his still alive at the time of publication. This genetic, X linked disorder of copper metabolism is always fatal in childhood. Diagnosis is evoked when is noted the conjunction of progressive cerebral degeneration, seizures, with pili torti and monilethrix. It can be asserted with the very low copper and cerulo-plasmin blood levels. Recognition of the disease in utero might be possible. New findings in skin' electron microscopy and hair' scanning electron microscopy are reported here. And two RX scanner of the brain have been performed.
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PMID:[Menkes' disease (new skin and hair ultrastructural abnormalities) (author's transl)]. 70 42

In an infant with Menkes's steely-hair syndrome, early treatment (from 21 days of age) with parenteral copper failed to halt the disease. In addition to urinary tract abnormalities, panlobular emphysema was present a finding not previously noted in the syndrome.
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PMID:Menkes's syndrome. Report of a patient treated from 21 days of age with parenteral copper. 74 1

The brindled mouse (Mobr) is a neurological mutant mouse with clinical and biochemical features closely similar to Kinky hair syndrome (KHS) in humans. Neuronal degeneration in the cerebral cortex and thalamic nuclei was the constant neuropathological lesions in the CNS of the male hemizygotes of this mutant (Yajima and Suzuki, 1978). Ultrastructurally, many cortical neurons contained enlarged mitochondria with prominent tubular or vesicular cristae, which were similar to those described in the Purkinje cells in the human KHS (Ghatak et al., 1972) and in the rat brain with copper deficiency (Prohaska and Wells, 1975). Such mitochondria were observed not only in the degenerating neurons but even in the otherwise normal-appearing cortical neurons, suggesting that the mitochondrial damage possibly related to the deficient activities of the copper containing enzymes (cytochrome oxidase, etc.) preceded the neuronal degeneration. Many mitochondria in the severely degenerated neurons contained numerous electron dense spicules of possible calcium. Although rare, similar morphological alteration of neuronal mitochondria was also noted in the female heterozygotes, indicating the presence of possible subclinical defect in copper transport in the heterozygotes as well.
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PMID:Neuronal degeneration in the brain of the brindled mouse. An ultrastructural study of the cerebral cortical neurons. 76 Mar 62

The kinky hair syndrome (KHS) is an X-linked defect of copper transport in man. An animal model is available in mutants at the X-linked mottled locus in mice. The defect does not involve the uptake of copper from the intestinal lumen but rather the transport of copper from intestinal cells. The reduced activity of several copper-dependent enzymes and the lower copper content of serum, liver, and probably brain account for the manifestations of the disorder which are evident at, or shortly after, birth. Intrauterine involvement is likely but prenatal diagnosis is not yet possible. Although the delivery of iron to the erythropoietic system, and its utilization, are impaired in nutritionally induced copper deficiency, as is neutrophil production, these processes appear normal in KHS. thus, adequate copper to carry them out is available in KHS. While there may be more than one transport system for copper (only one of which is affected in KHS) it is also possible that the hematopoietic tissue in KHS, like the intestinal cells, has abnormally high afficity for copper. The presence of multiple alleles at the KHS locus (and at other genetic loci) in man, which cause different degrees of reduction in copper transport, could account for variations in the susceptibility to copper deficiency observed in infant populations.
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PMID:Menkes' kinky hair syndrome: a genetic disease involving copper. 82 88

The cerebellar cortices in two patients with X-chromosome-linked copper malabsorption (Menkes kinky-hair disease) were examined with both the light and electron microscope. Somatic sprouts and grotesque dendritic arborization were among the obvious light microscopical changes. At the fine structural level, the Purkinje cells were characterized by the presence of somatic spines although the surviving granule cells had already descended. Most spines were parts of synaptic complexes, but some were unattached to any presynaptic element. Similar spines were also observed on dendritic trunks. Astrocytic gliosis and nonspecific endothelial cell changes were noted.
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PMID:Fine structure of the cerebellar cortex in Menkes Kinky-hair disease. X-chromosome-linked copper malabsorption. 83 87

Two Japanese infants with Menke's kinky hair syndrome are reported. The unusual finding in one infant was the absence of the hair abnormality characteristic of this disease; other findings were consistent with the diagnosis. It is suggested that hair abnormality cannot be relied upon for the diagnosis and that the term "kinky hair" is anappropriate. In its place "congenital hypocupraemia" is proposed as the diagnostic term to embrace patients with and without hair abnormality. Serum copper determination is a simple and reliable test in the diagnosis of this syndrome and should be done routinely in all male patients with unexpected deterioration. The angiographic features present in these patients with unexpected deterioration. The angiographic features present in these patients are characteristic but not pathognomonic of the disease. Subdural hygroma, a common finding, is the result of severe brain atrophy and little can be expected by surgical intervention.
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PMID:Congenital hypocupraemia syndrome with and without steely hair: report of two Japanese infants. 84 68


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