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

An autopsied patient with Menkes' kinky hair disease, who showed unusually long survival until the age of five years with typical neuropathological changes, was examined for distribution of neuronal depletion in the cerebral cortex, and the cerebellar changes were compared morphologically and immunohistochemically with those found in a younger patient (1 year 8 months old) reported previously. Neuronal loss in the cerebral cortex in the both cases, which was ill-defined and unassociated with gliosis, was preferentially distributed in the fifth and sixth layers, especially of the gyral bottom in almost all lobes in the older case. Therefore, this change was thought to be secondary to local ischemia caused by mechanical distortion at the stage of gyrus formation in addition to abnormal development. Ultrastructurally, a prominent increase of confronting cisternae (CC) complexes was found in the perikaryon and processes of Purkinje cells in both cases, and in the older patient CC complexes were arranged more densely and were transformed into concentric lamellar structures in the swollen dendrites. Immunohistochemically, the stainability of neurofilaments (NF, 200 kDa) in Purkinje cells, with or without somatic sprouts was faint or negative in the older patient compared with the marked or moderate positivity in the younger patient and age-matched controls. Empty baskets were absent and NF-positive axonal terminals and synaptophysin-positive granules on Purkinje cells were markedly decreased in both cases. These changes suggest that Purkinje cells degenerate progressively with time and that basket cells also are simultaneously involved.
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PMID:Menkes' kinky hair disease: morphological and immunohistochemical comparison of two autopsied patients. 202 48

We studied the brain metabolism in macular mutant mice (Ml/y, +/y), an appropriate model of Menkes kinky hair disease, using 31P- and 1H-NMR spectroscopy to clarify the pathophysiological mechanisms of disturbed nervous function. An analysis of in vivo 31P-NMR spectra showed a decreased phosphocreatine (PCr)/inorganic phosphate (Pi) ratio and decreased ATP levels and decreased intracellular pH in Ml/y mice at 9 days, suggesting energy failure in the brain. This associated decline in ATP levels may reflect multiple causative factors including disturbed mitochondrial respiration and ischemia secondary to circulatory failure. Brain metabolites, including PCr, creatine, lactate and 7 amino acids were easily detectable quantitatively and qualitatively by in vitro 1H-NMR spectrum. An elevation in lactate levels and a decline in PCr/creatine ratio in Ml/y mice at 9 days were also noted with an in vitro study, supporting the in vivo data. NMR spectroscopy is a useful and promising tool to obtain the information on brain metabolism.
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PMID:[A pathophysiological study of macular mutant mouse as a model of human Menkes kinky hair disease. II. Analysis of brain metabolism using 31P- and 1H-nuclear magnetic resonance spectroscopy]. 226 Dec 31

Both Atp7b (Wilson disease gene) and Atp7a (Menkes disease gene) have been reported to be trafficked by copper. Atp7b is trafficked to the bile duct canaliculi and Atp7a to the plasma membrane. Whether or not liver ischemia or ischemia-reperfusion modulates Atp7b expression and trafficking has not been reported. In this study, we report for the first time that the multi-specific metal transporter Atp7b is significantly induced and trafficked by both liver ischemia alone and liver ischemia-reperfusion, as judged by immunohistochemistry and Western blot analyses. Although hepatocytes also stained for Atp7b, localized intense staining of Atp7b was found on bile duct canaliculi. Inductive coupled plasma-mass spectrometry analysis of bile copper, iron, zinc, and manganese found a corresponding significant increase in biliary iron. In our attempt to determine if the increased biliary iron transport observed may be a result of altered bile flow, lysosomal trafficking, or glutathione biliary transport, we measured bile flow, bile acid phosphatase activity, and glutathione content. No significant difference was found in bile flow, bile acid phosphatase activity, and glutathione, between control livers and livers subjected to ischemia-reperfusion. Thus, we conclude that liver ischemia and ischemia-reperfusion induction and trafficking Atp7b to the bile duct canaliculi may contribute to preferential iron transport into bile.
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PMID:Liver ischemia and ischemia-reperfusion induces and trafficks the multi-specific metal transporter Atp7b to bile duct canaliculi: possible preferential transport of iron into bile. 1798 73