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

This study examines the current prevailing model of Oldowan technology-the opportunistic, least-effort strategy of stone tool making and using by early hominids. The sample includes the MNK chert factory site and three contemporaneous assemblages from Olduvai Gorge, all dated between 1.65 and 1.53 m.y.a. The analysis suggests that early hominids at Olduvai may have been selective, applying distinctive strategies in making and using tools depending on the different types of raw materials available to them. The preponderance of lava cores and near absence of flakes associated with the cores suggest that lava cores at Olduvai did not provide a source of flakes. They were primarily heavy-duty core tools, despite the fact that the majority of Olduvai lava is of excellent quality for flaking. Contrary to this pattern, the abundance of chert flakes and the lack of large chert cores suggest that the production of flakes was the most important strategy applied to chert. Original forms and flaking mechanics of the raw materials may have been important factors in the simultaneous application of the different, complementary strategies. The Oldowan tool-using strategy was dynamic and flexible, in response to changes in raw material availability. The use of chert between 1.65 and 1.53 m.y.a. was apparently related to the drastic decrease in flake production in lava and quartz. Finally, lack of initial reduction episodes of lava material challenges the idea of the stone cache strategy at Olduvai between 1.65 to 1.53 m.y.a.
J Hum Evol 1999 Dec
PMID:Tool-using strategies by early hominids at bed II, Olduvai Gorge, Tanzania. 1060 Mar 21

A 67-year-old woman had frequent subacute ileus, hearing difficulty, muscle atrophy and stroke-like episodes. Computed tomography revealed multiple low-density areas, which did not correlate with the vascular supply, in the cerebral cortex. She had metabolic disturbance comprising lactic acidosis and elevated pyruvate level. Her skeletal muscle biopsy specimen showed ragged-red fibers, and mitochondrial DNA analysis revealed a point mutation at position 3243, findings consistent with MELAS. Examination of her small intestine revealed a necrotic zone and numerous abnormal large mitochondria in the smooth muscle cells, vascular media and endothelium, and intestinal ganglion cells. The cerebral cortex showed multiple microcystic necrotic foci in cerebral cortex. Cactus-like pathology resembling the changes associated with Menkes' kinky hair disease and torpedoes were observed in the cerebellar Purkinje cells. The intestinal dysmotility due to MELAS and cerebellar changes were presumed to be associated with a disturbance of copper metabolism.
Acta Neuropathol 2000 Dec
PMID:Mitochondrial encephalomyopathy with lactic acidosis and stroke like episodes (MELAS) with prominent degeneration of the intestinal wall and cactus-like cerebellar pathology. 1107 25

Epileptic seizures are a common feature in Menkes disease, an X-linked genetic disorder of copper metabolism. Details of type of seizures are rarely reported. We report the evolution of infantile spasms in two patients with Menkes disease and the relation with subcutaneous administration of copper-histidine.
Epileptic Disord 2000 Dec
PMID:Infantile spasms and Menkes disease. 1117 54

A few patients with an affected CNS involving abnormalities in copper metabolism have been described that do not fit any known nosological entities such as Wilson's disease or Menkes' disease. Three sporadic patients (two men and one woman) were examined with involuntary movements and dysarthria associated with abnormal concentrations of serum copper, serum ceruloplasmin, and urinary copper excretion. The onset of neurological symptoms occurred at the age of 15 to 17 years. The common clinical symptoms were involuntary movements and dysarthria. The involuntary movements included dystonia in the neck, myoclonus in the shoulder, athetosis in the neck, and rapid orobuccal movements. The dysarthria consisted of unclear, slow, and stuttering speech. Two of the three patients did not have dementia. A cousin of the female patient had been diagnosed as having Wilson's disease and had died of liver cirrhosis. Laboratory findings showed a mild reduction in serum copper and ceruloplasmin concentrations, whereas urinary copper excretion was significantly reduced in all three patients. Two of the three patients showed a high signal intensity in the basal ganglia on T2 weighted brain MRI. In conclusion, the unique findings of involuntary movements, dysarthria, and abnormal serum copper and urinary copper concentrations suggest that the three patients may constitute a new clinical entity that is distinct from either Wilson's or Menkes disease.
J Neurol Neurosurg Psychiatry 2001 Dec
PMID:A new neurological entity manifesting as involuntary movements and dysarthria with possible abnormal copper metabolism. 1172 1

The pathogenesis of idiopathic adult onset dystonia (ID) is still unclear. Although neuropathologic studies did not reveal consistent abnormalities, electrophysiologic and neuroimaging findings point toward a disinhibition and overactivity of the frontal motor cortical areas caused by an altered basal ganglia outflow. The lentiform nuclei are assumed to play a major role in this scenario. Recent neurochemical analysis of brain tissue stimulated by transcranial ultrasound studies demonstrated an increased copper content of the lentiform nuclei in patients with ID. The shift of brain copper level may substantially influence neuronal activity causing a reduced inhibitory output from the lentiform nuclei to the motor cortex. The reason for the presumably altered copper metabolism is not clear, but preliminary findings suggest that reduced levels of the Menkes protein, a membrane ATPase exporting copper out of the cells, may be implicated. Disturbances of brain copper metabolism may explain various phenomena of ID; however, it needs to be determined whether these observations represent the basic pathogenetic mechanism of ID or reflect another as yet unidentified pathologic process.
Neurology 2001 Dec 26
PMID:Evidence for disturbances of copper metabolism in dystonia: from the image towards a new concept. 1175 12

X-linked recessive Menkes disease is a lethal disorder of copper metabolism, caused by defects in the ATP7A gene. About 15% of the mutations causing Menkes disease are partial gene deletions. We have previously demonstrated carrier diagnosis of deletions in heterozygotes by Southern blot analysis. As this technique is very time-consuming alternative methods are obviously of high value. Multiplex polymerase chain reaction (PCR), reverse transcription PCR (RT-PCR) and spanning the deletion on genomic DNA can all be used for detection of partial gene deletions in male patients, but only spanning of the deletion can be applied for carrier detection. Simple multiplex PCR is not applicable for carrier detection because the normal allele of ATP7A will be PCR amplified thus masking the deletion. Here, we demonstrate, in addition to spanning of the deletion on genomic DNA, carrier detection based on the use of a previously unrecognized polymorphism in intron 13 of ATP7A in combination with previously identified intragenic polymorphic markers. We show that these intragenic markers can be used for carrier detection, not only indirectly by determining segregation of the disease related allele but also directly if located within the deleted region. We demonstrate determination of the carrier status of 21 at-risk carriers.
Clin Genet 2002 Dec
PMID:X-linked recessive Menkes disease: carrier detection in the case of a partial gene deletion. 1248 91

Menkes disease is an X-linked recessive lethal disorder of copper metabolism, caused by defects in the ATP7A gene. Partial gene deletions comprise about 15% of the mutations causing Menkes disease. We have previously demonstrated identification of partial ATP7A deletions in patients by Southern blot analysis. In the present study, we report the use of three fast and reliable polymerase chain reaction (PCR)-based methods for the identification of partial ATP7A deletions in Menkes disease patients. First we demonstrate the use of multiplex PCR, a fast method for identification and rough localization of partial gene deletions, in which two exons of ATP7A are coamplified. Second, we present PCR amplification of genomic DNA across the deletion junctions, a method enabling identification of the deletion breakpoints and hence the exact size of the deletion. Finally, application of reverse transcription PCR (RT-PCR) for identification and localization of gene deletions at the cDNA level is demonstrated. By studying the mutation at the cDNA level the predicted effect of the mutation on the amino acid sequence and consequently the protein structure and function can be inferred. We demonstrate characterization of partial gene deletions in five patients, and in three of these we were able to determine the breakpoint sequences.
Clin Genet 2002 Dec
PMID:X-linked recessive Menkes disease: identification of partial gene deletions in affected males. 1248 92

Menkes disease (MD) is an X-linked multisystemic lethal disorder of copper metabolism dominated by neurodegenerative symptoms and connective tissue disturbances. MD results from mutations in the ATP7A gene, which encodes a membrane-bound copper transporting P-type ATPase located in the trans-Golgi network. In this study we describe screening of 383 unrelated patients affected with Menkes disease for gross deletions in ATP7A gene and finding of 57 patients. The present data suggests that gross deletion of ATP7A is the disease-causing mutation in 14.9% of the Menkes disease patients. Except for a few cases, gross gene deletions result in the classical form of Menkes disease with death in early childhood.
Hum Mutat 2003 Dec
PMID:Screening of 383 unrelated patients affected with Menkes disease and finding of 57 gross deletions in ATP7A. 1463 5

The Cu-ATPase ATP7A (MNK) is localized in the trans-Golgi network (TGN) and relocalizes in the plasma membrane via vesicle-mediated traffic following exposure of the cells to high concentrations of copper. Rab proteins are organelle-specific GTPases, markers of different endosomal compartments; their role has been recently reviewed (Trends Cell Biol. 11(2001) 487). In this article we analyze the endosomal pathway of trafficking of the MNK protein in stably transfected clones of CHO cells, expressing chimeric Rab5-myc or Rab7-myc proteins, markers of early or late endosome compartments, respectively. We demonstrate by immunofluorescence and confocal and electron microscopy techniques that the increase in the concentration of copper in the medium (189 microM) rapidly induces a redistribution of the MNK protein from early sorting endosomes, positive for Rab5-myc protein, to late endosomes, containing the Rab7-myc protein. Cell fractionation experiments confirm these results; i.e., the MNK protein is recruited to the endosomal fraction on copper stimulation and colocalizes with Rab5 and Rab7 proteins. These findings allow the first characterization of the vesicles involved in the intracellular routing of the MNK protein from the TGN to the plasma membrane, a key mechanism allowing appropriate efflux of copper in cells grown in high concentrations of the metal.
Exp Cell Res 2003 Dec 10
PMID:Endosomal trafficking of the Menkes copper ATPase ATP7A is mediated by vesicles containing the Rab7 and Rab5 GTPase proteins. 1464 59

The HAH1 metallochaperone is a key protein implicated in copper homeostasis in human cells. Using as solid-phase based assay completed with Biacore studies, we provided evidence that HAH1 forms homo-dimers in the presence of copper. Biacore analysis allowed us to determine the kinetic parameters of this interaction, characterised by an apparent affinity constant of 6muM. Moreover, we demonstrated that copper-loaded HAH1 interacts independently with each of the six individual metal-binding domains of the copper-translocating Menkes ATPase. Finally, the homo-dimerisation of the metallochaperone was confirmed in living cells by using fluorescence resonance energy transfer. Results have been discussed in the context of intracellular copper control.
Biochem Biophys Res Commun 2004 Dec 10
PMID:Copper-mediated homo-dimerisation for the HAH1 metallochaperone. 1553 Apr 4


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