Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022716 (Menkes)
 1,057 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

We report a detailed molecular analysis of the genomic structure of the Menkes disease gene (MNK; ATP7A). There are 23 exons in ATP7A covering a genomic region of approximately 140 kb. The size of the individual coding exons varies between 77 and 726 bp, and introns vary in size between 196 bp and approximately 60 kb. All of the splice sites obey the consensus GT-AG rule except the splice donor of intron 9, which is GC instead of GT. The exon following this rare splice donor variant is alternatively spliced. A PGAM pseudogene and two highly polymorphic CA repeats map to introns within the gene. The structure is very similar to that of the closely related Wilson disease gene (WND; ATP7B). From exon 5 (exon 3 in ATP7B) to the end, all of the splice sites occur at exactly the same nucleotide positions as in the WND gene, except for the boundary between exons 17 and 18 (exons 15 and 16 in ATP7B) and a single codon difference at the boundary between exons 4 and 5 of the MNK gene (exons 2 and 3 in ATP7B). In contrast to the WND gene, in which the first four of six metal binding domains are contained in 1 exon, metal binding domains 1 to 4 are divided over 3 exons. The striking similarity of the MNK and WND genes at the genomic level is consistent with their relatively recent divergence from a common ancestral gene.
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PMID:Molecular structure of the Menkes disease gene (ATP7A). 749 81

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

We describe the cloning and characterization of a new human Xq13 gene (XH2), extending over a 220 kb genomic stretch between MNK and DXS56. The gene, which undergoes X-inactivation, contains a 4 kb open reading frame and encodes a putative NTP-binding nuclear protein homologous to several members of the helicase II superfamily. The murine homologue maps to the syntenic genetic interval, between Pgk1 and Xist. In situ hybridization studies in mouse reveal precocious, widespread expression of the murine homologue of XH2 at early stages of embryogenesis, and more restricted expression during late developmental stages and at birth. XH2 is a new member of an expanding family of proven and putative helicases, sharing six conserved, collinear domains. In particular, the XH2 protein shows homology with yeast RAD54. Type II helicases have been implicated in nucleotide excision repair and the initiation of transcription. This new gene, represents a potential candidate for several genetic disorders mapped to human Xq13.
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PMID:Cloning and characterization of a new human Xq13 gene, encoding a putative helicase. 787 12

Human CD3AK and LAK cells were prepared from peripheral blood mononuclear cells (PBMC) by culturing them in recombinant IL-2 (rIL-2, 30 mu/ml) and anti-CD3 monoclonal antibody, and in rIL-2 alone (300/ml), respectively. By MTT assay, it was found that the PBMC, when cultured in the presence of anti-CD3/rIL-2, proliferated more actively and persistently than PBMC cultured in the presence of rIL-2 alone. In vitro cytotoxicity assay showed that CD3AK cells had stronger killing activity against a poorly differentiated human gastric adenocarcinoma cell line MNK 45 than LAK cells did. Winn's assay at an E/T ratio of 20 carried out in nude mice also indicated that CD3AK cells were more effective than LAK cells in tumor growth inhibition. When the nude mice were inoculated with MNK 45 admixed with CD3AK, none of them developed tumor whereas those inoculated with either MNK 45 or MNK 45 admixed with LAK cells all developed tumor. The results indicate that CD3AK would be a better choice than LAK for the adoptive immunotherapy of human stomach cancer.
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PMID:[Experimental study of the anti-tumor activity of CD3AK against human gastric cancer cell line in vitro and in vivo]. 792 59

Fibroblast cultures from 12 unrelated patients with classical Menkes disease were analyzed for mutations in the MNK gene, by reverse transcription-PCR (RT-PCR) and chemical cleavage mismatch detection. Mutations were observed in 10 patients, and in each case a different mutation was present. All of the mutations would be predicted to have adverse effects on protein expression. Mutations that resulted in splicing abnormalities, detected by RT-PCR alone, were observed in six patients and included two splice-site changes, a nonsense mutation, a missense mutation, a small duplication, and a small deletion. Chemical cleavage analysis of the remaining six patients revealed the presence of one nonsense mutation, two adjacent 5-bp deletions, and one missense mutation. A valine/leucine polymorphism was also observed. These findings, combined with the prior observation of deletions in 15%-20% of Menkes patients, suggest that Southern blot hybridization and RT-PCR will identify mutations in the majority of patients.
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PMID:Diverse mutations in patients with Menkes disease often lead to exon skipping. 797 50

Little is known at the molecular level about the homeostatic control of heavy-metal concentrations in mammals. Recently, however, two human diseases that disrupt copper transport, Menkes disease and Wilson disease, were found to be caused by mutations in two closely related genes, MNK and WND, which encode proteins belonging to the P-type ATPase family of cation transporters. The MNK and WND proteins are unique in having at their amino termini six copies of a sequence that is remarkably similar to sequences previously found in bacterial heavy-metal-resistance proteins and in a P-type ATPase that appears to form part of a bacterial copper homeostatic system. These two human ATPases are the first putative heavy-metal transporters to be discovered in eukaryotes.
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PMID:Wilson disease and Menkes disease: new handles on heavy-metal transport. 809 5

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. Unlike Menkes' disease, most patients with OHS have mild submentality. We report a case of OHS with severe central nervous system involvement and muscular atrophy in a 34-year-old male. He had psychomotor retardation and seizures since early childhood and now presented severe mental retardation and generalized muscular atrophy in addition to characteristic facial appearance, hyperelasticity of the skin and joint subluxation. Laboratory investigations revealed a low serum copper and ceruloplasmin level as well as intestinal non-absorption of copper. Radiographic imaging showed occipital exostoses, bladder diverticula, tortuosity of the peripheral vein and osteoporosis of the skeletal bones. The activity of lysyl oxidase, a copper-enzyme involved in cross-link formation in collagen, was found to be decreased in a skin-biopsy specimen. Electron-microscopic investigation of a muscle biopsy showed irregularity of the myofibrillar network and accumulation of concentric laminated bodies in the subsarcolemmal regions.
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PMID:Central nervous system involvement and generalized muscular atrophy in occipital horn syndrome: Ehlers-Danlos type IX. A first Japanese case. 809 5

Little is known about the mechanism by which lymphokine-activated killer (LAK) cells and natural killer (NK) cells recognize and lyse target cells. We undertook this study to investigate the effects of target cell membrane modification by sodium periodate (PI) on the lysis of tumor cells by human and murine LAK cells (HLAK, MLAK) and NK cells (HNK, MNK). LAK and NK cells were generated and used as effector cells in 4-hr 51Cr release assays against a variety of PI-treated and untreated target cells. PI significantly increased the MLAK cell-mediated lysis of YAC and MH134 tumor cells, but had no effect on the MNK lysis of YAC or MH134 tumor cells. PI had no effect on the HLAK or HNK lysis of YAC or MH134 tumor cells. PI had no effect on the MLAK or MNK lysis of K562 or U937 human tumor cells. Similarly, PI had no effect on the HLAK lysis of K562, but did significantly increase the HNK lysis of K562. PI increased both the HLAK and HNK lysis of U937. Cold target inhibition studies revealed that PI-treated YAC cells inhibited the MLAK cell-mediated lysis of untreated YAC cells. The variable effects of PI on LAK cell- and NK cell-mediated lysis support the hypothesis that LAK cells are a distinct population of cells rather than a subpopulation of NK cells on the basis of mechanism of target cell recognition. The results of the cold target inhibition study suggest that PI-treated tumor cells are identified by effector cells in a manner similar to that of untreated cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Target cell membrane modification and susceptibility to lymphokine-activated killer cell-mediated lysis. II. Sodium periodate has a differential effect on the lysis of human and murine tumor cells. 812 Nov 71

Wilson disease (WD) is an autosomal recessive disorder of copper transport, resulting in copper accumulation and toxicity to the liver and brain. The gene (WD) has been mapped to chromosome 13 q14.3. On yeast artificial chromosomes from this region we have identified a sequence, similar to that coding for the proposed copper binding regions of the putative ATPase gene (MNK) defective in Menkes disease. We show that this sequence forms part of a P-type ATPase gene (referred to here as Wc1) that is very similar to MNK, with six putative metal binding regions similar to those found in prokaryotic heavy metal transporters. The gene, expressed in liver and kidney, lies within a 300 kb region likely to include the WD locus. Two WD patients were found to be homozygous for a seven base deletion within the coding region of Wc1. Wc1 is proposed as the gene for WD.
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PMID:The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene. 829 39


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