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

Numerous control systems are involved in the growth and differentiation of chondro-osseous tissue. Theoretically, the failure of each single step will result in a peculiar skeletal dysplasia. The resulting disorders are caused by errors in the metabolism of collagen, minerals, complex carbohydrates and the protein of the ground substance. Skeletal dysplasias with a known or probable metabolic base include osteogenesis imperfecta, osteoectasia with macrocranium, Menkes syndrome, the mucopolysaccharidoses and hypophosphatasia.
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PMID:[The metabolic basis of generalized skeletal dysplasia (author's transl)]. 82 73

The author presents and discusses the anaesthetic implications of a four-month-old infant with Menkes' syndrome who required tracheostomy. Menkes' syndrome is an X-linked recessive disorder of copper absorption and metabolism. Defective processing of copper results in abnormalities of several enzyme systems leading to severe dysfunction of multiple organ systems. Due to the progressive nature of this disorder and its severe effects on several different organ systems, most importantly the central nervous system, these children frequently require anaesthetic care during imaging procedures such as MRI or during various surgical operations. The high prevalence of seizure disorders, gastroesophageal reflux with the risk of aspiration, and airway complications related to poor pharyngeal muscle control are of concern to the anaesthetist. In addition, defective collagen formation, similar to that seen in Ehlers-Danlos syndrome, may be present. Identification of these associated conditions during the preoperative examination will guide the selection of appropriate, safe anaesthetic care for these children.
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PMID:Anaesthetic considerations in the child with Menkes' syndrome. 139 61

Occipital horn syndrome (OHS; Ehlers-Danlos syndrome type IX) belongs to the category of the copper metabolism disorders and is at present being investigated biochemically as is Menkes disease. We report a case of OHS in a 34-year-old male, which we believe to be the first Japanese case. He had been noted to have psychomotor retardation since his early childhood and now presents severe psychomotor retardation and muscle atrophy. He shows characteristic facial appearance, hyperelasticity of the skin, joint subluxation and generalized muscular atrophy. Laboratory investigations revealed a low serum copper and ceruloplasmin level as well as intestinal non-absorption of copper. Radiologic imagings showed occipital exostoses and bladder diverticula. The activity of lysyl oxidase, a copper-dependent enzyme involved in cross-link formation in collagen, was decreased in a skin-biopsied specimen. Electronmicroscopic investigation of a muscle biopsy showed irregularity of the myofibrillar network and accumulation of the concentric laminated bodies in the subsarcolemmal regions.
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PMID:[Occipital horn syndrome (Ehlers-Danlos syndrome type IX) with severe psychomotor retardation and muscle atrophy--a first Japanese case]. 168 78

The amount of lysine in collagen is only 3 or 4% of total aminoacids, but it has an important function in the constitution of the cross-links between the molecules to built the fibrils and the fibers of collagen. For this function, some lysine molecules must be hydroxylated and other oxidized to aldehyde compounds. Some deficits in these metabolic pathways are responsible for heritable diseases of the connectivite tissue as types IV and IX of the Ehlers-Danlos syndrome, lathyrism, the Menkes kinky hair syndrome, Cutis-Laxa or the type II of osteogenesis imperfecta. The contribution to fibrosis is also discussed.
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PMID:[Lysine and collagen]. 190 95

In Menkes' disease, a severe disturbance of copper handling appears to render copper unavailable for copper-requiring processes. We have measured the activity of lysyl oxidase, the copper-dependent enzyme that initiates the cross-linking of collagen and elastin, in extracts of skin and aorta obtained at autopsy from a patient with unusually marked connective tissue manifestations, and found it to be only 6-12% of normal, thus suggesting a basis for these alterations.
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PMID:Markedly reduced activity of lysyl oxidase in skin and aorta from a patient with Menkes' disease showing unusually severe connective tissue manifestations. 197 62

The authors describe a patient who presented from birth on a severe involvement of connective tissues with pathological fractures, lack of auricular cartilage, hyperlaxity of fingers and cutis laxa with deep folds, all suggestive of derangements of collagen and elastin. Hypothermia at 24 hours of age should have already indicated the possibility of Menkes' syndrome. From the 3rd month on, the patient presents a neurological deterioration and a myoclonic epilepsy which is resistant to treatment. Craniocerebral tomodensitometry revealed, with time, a cerebral atrophy and subdural hematomas. Angiodysplasia of a coronary artery was seen at cardiac echocardiography. Undetectable levels of serum copper and ceruloplasmin, and an increased uptake of copper by fibroblasts in vitro confirmed the diagnosis of Menkes' syndrome. Electron microscopy of a skin biopsy disclosed a desmosomal anomaly in the epidermis. Desmosomes stay apart suggesting an alteration of the interdesmosomal cement.
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PMID:[Menkes disease. Report of a case with pronounced involvement of connective tissues and changes in epidermal desmosomes]. 270 74

Lysyl oxidase activity against both collagen and elastin substrates has been examined in the culture medium of skin fibroblasts derived from unrelated patients with Menkes' syndrome and from control subjects. The medium of three Menkes' fibroblast lines showed 3--30% of the activity present in the medium of control fibroblasts, against a purified collagen substrate. Lysyl oxidase activity in the culture medium of two of the Menkes' fibroblast lines was also examined by using a crude aortic-elastin substrate and was similarly decreased in comparison with that in the medium of control fibroblasts. Lysyl oxidase activity in the medium of a fourth fibroblast line, derived from a foetus with Menkes' syndrome, was 42% of that in the medium of control fibroblasts derived from a 1-day-old baby against a collagen substrate, and 26% of that in control fibroblast medium against an elastin substrate. The copper content of the cell layers of the Menkes' fibroblast cultures was elevated in comparison with normal fibroblast cultures, as has previously been reported to be characteristic of such cells. It is suggested that the decrease in lysyl oxidase activity would help to explain the connective tissue defects observed in Menkes' syndrome, and that this reduction, in conjunction with the elevated concentrations of cellular copper, would support the hypothesis that a functional intracellular copper deficiency exists in Menkes' syndrome.
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PMID:Reduced lysyl oxidase activity in skin fibroblasts from patients with Menkes' syndrome. 611 84

Cultured fibroblasts of 13 patients with the Menkes syndrome and two with a new subtype (type IX) of the Ehlers-Danlos syndrome (E-D IX patients) showed many very similar abnormalities in their copper and collagen metabolism. Both cell types had markedly increased copper concentrations and 64Cu incorporation, and this cation accumulated in metallothionein or a metallothionein-like protein, as previously established for Menkes cells. Histochemical staining indicated that copper was distributed diffusely throughout the cytoplasm in both cell types, this location being consistent with the accumulation in metallothionein. Both fibroblast types also had markedly low lysyl oxidase activity and distinctly increased extractability of newly synthesized collagen, whereas no abnormalities were present in cell viability, duplication rate, prolyl 4-hydroxylase activity, or collagen synthesis rate. A high negative correlation (P less than 0.001) was found in the pooled group of Menkes and E-D IX cells between cellular copper concentration (r = 0.804) or 64Cu incorporation (r = 0.863) and the logarithm of lysyl oxidase activity. There was also a high positive correlation (P less than 0.001) between cellular copper concentration and incorporation (r = 0.869). One of the two E-D IX patients was also shown to have similar changes in lysyl oxidase activity and collagen extractability in the skin biopsy specimen, suggesting that the abnormalities observed in cultured cells are similar to those present in vivo. The only distinct abnormality found in the cells of the parents of the E-D IX patients was an increased 64Cu incorporation in those of the mother, this finding being consistent with X-linked inheritance of the disorder.
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PMID:Alterations in copper and collagen metabolism in the Menkes syndrome and a new subtype of the Ehlers-Danlos syndrome. 614 Sep 52

Lysyl oxidase (LO) is an extracellular copper-dependent enzyme that catalyzes the initial reaction in the formation of lysine or hydroxylysine-derived crosslinks during collagen biosynthesis. We have isolated a cDNA for human LO from skin fibroblast poly(A+)RNA by PCR using primers based on the recently published sequence of human LO. This cDNA probe detects a major mRNA of 4.2 kb on Northern blots of RNA from normal fibroblasts. The level of LO mRNA was not significantly affected by cell density or by ascorbate treatment. Treatment of skin fibroblasts with hydralazine (50 microM), which increases the mRNAs for both the alpha and the beta subunits of prolyl hydroxylase (PH) and the mRNAs for lysyl hydroxylase, also increased LO mRNA by fourfold over a 72-h time course. In contrast, hydralazine dramatically decreased the mRNAs for alpha 1(I) collagen. Administration of minoxidil (500 microM), which specifically decreases LH activity without affecting PH activity or collagen biosynthesis in skin fibroblasts, stimulated the level of LO mRNA. Neither the administration of penicillamine (100 microM), which interferes with collagen cross-linking, nor the administration of beta-aminopropionitrile, which is a strong irreversible inhibitor of LO, to fibroblasts significantly changed the levels of LO mRNA over a 72-h time course. However, bleomycin (0.6 microgram/ml) significantly decreased the 4.2-kb LO mRNA in contrast to the levels of the alpha 1(I) collagen mRNAs, which were unchanged. No significant change was observed in the steady-state levels of LO mRNAs in fibroblasts isolated from patients with certain connective tissue disorders, including Marfan syndrome, Menkes disease, cutis laxa, and pseudoxanthoma elasticum.
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PMID:Regulation of lysyl oxidase mRNA in dermal fibroblasts from normal donors and patients with inherited connective tissue disorders. 750 9

Xenografting can be accomplished by using encapsulated cells in the alginate microcapsule. Using this technique, the experiment was made to investigate the stroma-promoting factors that were produced by the encapsulated differentiated (MKN-28) and undifferentiated (KATO-III) gastric cancerous cell lines. Fibronectin (FN) in the medium was quantified by single culture with the human fibroblast cell line (CCD-32Lu) and coculture with CCD-32Lu and the encapsulated MKN-28 ro KATO-III. Then following this procedure, each capsule including the gastric cancerous cells was subcutaneously transplanted into Wistar Rats. After 14 days, the surrounding tissues of the microcapsules were stained, and the localization of type III collagen, 4 and 6 chondroitin sulfate, and FN were observed by immunohistochemical stainings. The concentration of FN in both single culture and coculture medium gradually increased, especially in the medium complemented with KATO-III and CCD-32Lu. The measured point after 48 hours demonstrated the obvious increase compared to the single culture and coculture medium. Upon the histological comparison, it was found that the stromal proliferation around the tissue transplanted the microcapsules including MKN-28 or KATO-III were distributed more abundantly than the transplantation of microcapsules only. However, no difference was noted between the stroma of MNK-28 and KATO-III. In conclusion, this study suggests that any stroma-promoting factor is produced by the gastric cancerous cells.
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PMID:[Stromal changes in cancer. Studies on changes of stroma promoted by gastric cancerous cells using alginate microcapsules]. 782 49


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