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)

Skin fibroblasts from normal subjects and from patients with Menkes' disease did not demonstrate any significant differences in morphologic or growth characteristics when cultured in medium without added copper. Addition of CuCl2 to the medium caused a reduction in the growth rate of the fibroblasts. Menkes' fibroblasts were more sensitive to copper than normal cells. Concentrations greater than 50 micrograms CuCl2/ml of medium caused extensive cell death especially in the mutant cells. The rate of DNA synthesis in Menkes' fibroblasts was reduced in the presence of 2--100 micrograms CuCl2/ml. Normal cells showed a reduction in DNA synthesis at CuCl2 concentrations greater than 50 micrograms/ml, whereas at concentrations between 2 and 30 micrograms/ml the rate of DNA synthesis was increased. These findings indicate that CuCl2 is more toxic to Menkes' than to normal fibroblasts and suggest that a similar response of neuronal cells may occur in the patients in vivo.
 ...
PMID:Effect of copper on Menkes' and normal cultured skin fibroblasts. 743 75

Tetracycline (TC) exerts DNA damaging properties which are accelerated in the presence of copper(II). Thereby, reactive oxygen species are generated. We investigated, if copper-accumulating cells show a higher sensitivity to TC compared to normal cells. Fibroblasts with an increased copper content were derived from patients of two genetic disorders, Wilson disease (WD) and Menkes disease (MD). Cytotoxic and genotoxic effects of TC were investigated in different human fibroblasts. The inhibition of cell growth by TC was measured in two normal fibroblast lines, fibroblast lines of two patients with WD and one patient with MD. While TC inhibited cell growth at similar concentrations in normal fibroblasts and the MD fibroblasts, the WD cells were much more sensitive. Furthermore, an increased inhibition of DNA synthesis and an enhanced induction of unscheduled DNA synthesis (UDS) was found in WD cells after a TC-treatment compared to normal cells.
 ...
PMID:Enhanced cyto- and genotoxicity of tetracycline in Wilson disease fibroblasts. 756 16

The gene defective in Menkes disease, an X-linked recessive disturbance of copper metabolism, has been isolated and predicted to encode a copper-binding P-type ATPase. We determined the complete exon-intron structure of the Menkes disease gene, which spans about 150 kb of genomic DNA. The gene contains 23 exons, and the ATG start codon is in the second exon. All of the exon-intron boundaries were sequenced and conformed to the GT/AT rule, except for the 5' splice site of intron 9. A preliminary comparison demonstrated a striking similarity between the exon structures of the Menkes and Wilson disease genes, giving insight into their evolution.
 ...
PMID:Characterization of the exon structure of the Menkes disease gene using vectorette PCR. 760 65

Menkes disease is an X linked recessive disorder of copper metabolism characterised by neurological symptoms and connective tissue manifestations. The defective gene in Menkes disease has recently been isolated and the gene product is predicted to be a copper transporting ATPase. The diagnosis of Menkes disease has hitherto been performed by biochemical analysis, based on intracellular accumulation of copper. Cloning the gene opened up the possibility of establishing precise and reliable carrier and prenatal diagnosis by defining the molecular defect. In this report we describe the partial deletion of the Menkes gene in a patient who had inherited the mutation from his phenotypically normal mother. This information enabled us to perform prenatal diagnosis by direct mutation analysis of the mother's sixth pregnancy and we detected the same deletion, indicating that the male fetus was affected. This first prenatal diagnosis of Menkes disease by direct mutation analysis shows some advantages of DNA analysis compared to biochemical diagnosis.
 ...
PMID:First trimester prenatal diagnosis of Menkes disease by DNA analysis. 781 18

Bacterial plasmids contain specific genes for resistances to toxic heavy metal ions including Ag+, AsO2-, AsO4(3-), Cd2+, Co2+, CrO4(2-), Cu2+, Hg2+, Ni2+, Pb2+, Sb3+, and Zn2+. Recent progress with plasmid copper-resistance systems in Escherichia coli and Pseudomonas syringae show a system of four gene products, an inner membrane protein (PcoD), an outer membrane protein (PcoB), and two periplasmic Cu(2+)-binding proteins (PcoA and PcoC). Synthesis of this system is governed by two regulatory proteins (the membrane sensor PcoS and the soluble responder PcoR, probably a DNA-binding protein), homologous to other bacterial two-component regulatory systems. Chromosomally encoded Cu2+ P-type ATPases have recently been recognized in Enterococcus hirae and these are closely homologous to the bacterial cadmium efflux ATPase and the human copper-deficiency disease Menkes gene product. The Cd(2+)-efflux ATPase of gram-positive bacteria is a large P-type ATPase, homologous to the muscle Ca2+ ATPase and the Na+/K+ ATPases of animals. The arsenic-resistance system of gram-negative bacteria functions as an oxyanion efflux ATPase for arsenite and presumably antimonite. However, the structure of the arsenic ATPase is fundamentally different from that of P-type ATPases. The absence of the arsA gene (for the ATPase subunit) in gram-positive bacteria raises questions of energy-coupling for arsenite efflux. The ArsC protein product of the arsenic-resistance operons of both gram-positive and gram-negative bacteria is an intracellular enzyme that reduces arsenate [As(V)] to arsenite [As(III)], the substrate for the transport pump. Newly studied cation efflux systems for Cd2+, Zn2+, and Co2+ (Czc) or Co2+ and Ni2+ resistance (Cnr) lack ATPase motifs in their predicted polypeptide sequences. Therefore, not all plasmid-resistance systems that function through toxic ion efflux are ATPases. The first well-defined bacterial metallothionein was found in the cyanobacterium Synechococcus. Bacterial metallothionein is encoded by the smtA gene and contains 56 amino acids, including nine cysteine residues (fewer than animal metallothioneins). The synthesis of Synechococcus metallothionein is regulated by a repressor protein, the product of the adjacent but separately transcribed smtB gene. Regulation of metallothionein synthesis occurs at different levels; quickly by derepression of repressor activity, or over a longer time by deletion of the repressor gene at fixed positions and by amplification of the metallothionein DNA region leading to multiple copies of the gene.
 ...
PMID:Newer systems for bacterial resistances to toxic heavy metals. 784 81

DNA encoding a P-type ATPase was cloned from the cyanobacterium Synechococcus 7942. The cloned ctaA gene encodes a 790-amino acid polypeptide related to the CopA Cu(2+)-uptake ATPase of Enterococcus hirae, to other known P-type ATPases, and to the candidate gene products for the human diseases of copper metabolism, Menkes disease and Wilson disease. Disruption of the single chromosomal gene in Synechococcus 7942 by insertion of an antibiotic-resistance cassette results in a mutant cell line with increased tolerance to Cu2+ compared with the wild type.
 ...
PMID:P-type ATPase from the cyanobacterium Synechococcus 7942 related to the human Menkes and Wilson disease gene products. 793 23

The possibility of gene therapy for patients with Menkes or Gaucher's disease has been improved by the isolation of a promising candidate gene and production of a mouse model, respectively. Many mutations of mitochondrial DNA are being associated with mitochondrial encephalomyopathies, and protection of the resultant biochemical deficiency can be achieved with a remarkably low percentage of normal mitochondrial DNA. The correlation between mutation, biochemical deficiency, and neurologic consequence, however, remains frustratingly obscure. Gas chromatography-mass spectrometric urinalysis is becoming increasingly important in the diagnosis of metabolic disorders and is revealing new and unexpected deficiencies.
 ...
PMID:Neurologic complications of inherited mitochondrial abnormality, and neurologic consequences of inborn errors of metabolism. 850 13

There has been considerable progress in chromosome mapping and gene identification in several severe hereditary skin diseases, leading to changes in genetic counseling. It is now possible to propose antenatal diagnosis to couples at risk based on an analysis of foetal DNA from trophoblast biopsies performed as early as the 9th week of gestation. Antenatal can be made by direct analysis based on identifying the mutation known in the family at risk or on indirect analysis based on the linkage disequilibrium of the allele or alleles associated with the disease in the family at risk. This method has already been shown to be effective in recessive dystrophic bullous epidermolysis, lethal Herlitz's junctional bullous epidermolysis, bullous ichthyosiform hereditary erythroderma, von Recklinghausen's neurofibromatosis, tyrosinase negative oculocutaneous albinism, Gorlin's syndrome, anhidrotic ectodermic dysplasia and Menkes disease. These techniques will replace microscopic examination of ultrastructure in foetal skin biopsies performed at 20 weeks gestation. They can also be applied to diseases where the antenatal diagnosis now relies on enzyme function tests or DNA distribution. Improving genetic counselling in these diseases requires the identification of the implicated genes, identification of the causal mutations in the families at risk and development of genetic markers for these diseases.
 ...
PMID:[Prenatal diagnosis of cutaneous genetic diseases by the study of fetal DNA]. 852 12

Our group has developed more than 600 DNA markers to build a map of the canine genome. Of these markers, 125 correspond to genes (anchor loci). Here we report the first six autosomal genes assigned to canine chromosomes by fluorescence in situ hybridization (FISH), using cosmid DNA: adenine phosphoribosyl transferase on Chromosome (Chr) 3; creatine kinase muscle type on Chr 4; pyruvate kinase liver and red blood cell type on Chr 2; and colony-stimulating factor-1 receptor, glucose transporter protein-2, and tumor protein p53 on Chr 5. These assignments are based on the karyotype proposed by Stone and associates (Genome 34, 407, 1991) using high-resolution techniques. In addition, we have assigned the Menkes gene to the X Chr of the dog.
 ...
PMID:Chromosomal assignment of seven genes on canine chromosomes by fluorescence in situ hybridization. 866 96

Copper is a trace element necessary for the normal function of several important enzymes but copper homeostasis is still poorly understood. In recent years remarkable progress has been made in this field following the isolation of the gene defective in Menkes disease. Menkes disease and occipital horn syndrome are X-linked recessive disorders, demonstrating the vital importance of copper, which is also highly toxic in excessive amounts. Its destructive effects are reflected in the autosomal recessive Wilson's disease. Progressive neurodegeneration and connective tissue disturbances are the main manifestations of Menkes disease. Although many patients present a severe clinical course, variable forms can be distinguished, and the occipital horn syndrome has been suggested to be a mild allelic form. The Menkes locus is mapped to Xq13.3 and the gene defective in Menkes disease has been isolated by positional cloning. The gene is predicted to encode an energy-dependent copper-binding protein, the first intracellular copper transporter described in eukaryotes. Isolation of the gene and subsequent characterization of the exon-intron organization now enables the establishment of DNA-based diagnostic methods. Furthermore, identification of the Menkes disease gene led to other important findings, such as isolation of its mouse homologue, confirming the allelic relationship between Menkes disease and occipital horn syndrome, and isolation of the defective genes in Wilson's disease and its rat homologue.
 ...
PMID:Menkes disease: recent advances and new insights into copper metabolism. 873 40


<< Previous 1 2 3 4 5 6 7 Next >>