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Kohtaro Asayama - One of the best experts on this subject based on the ideXlab platform.
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Cerebellar superoxide dismutase expression in Menkes' Kinky Hair disease: an immunohistochemical investigation.
Acta neuropathologica, 1995Co-Authors: Noriyuki Shibata, Asao Hirano, Makio Kobayashi, Takahiko Umahara, Toru Kawanami, Kohtaro AsayamaAbstract:This comparative immunohistochemical study deals with the expression of the cytosolic Cu/Zn-binding and mitochondrial Mn-dependent superoxide dismutases (SODs) in the cerebella of five patients with Menkes' Kinky Hair disease (MKHD) and five age-matched controls. Several cell types, including Purkinje cells and reactive astrocytes, of all MKHD patients examined were intensely stained by an antibody to Mn SOD, but not by an anti-Cu/Zn SOD antibody. By contrast, the cells of the five controls reacted very weakly or not at all with the anti-Mn SOD antibody, but were strongly reactive with the antibody to Cu/Zn SOD. These results suggest that the increased Mn SOD immunoreactivity in MKHD reflects enzyme induction as a protective mechanism against the highly toxic superoxide anion generated under the disease conditions.
Asao Hirano - One of the best experts on this subject based on the ideXlab platform.
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Cerebellar expression of copper chaperone for superoxide, cytosolic cu/zn-superoxide dismutase, 4-hydroxy-2-nonenal, acrolein and heat shock protein 32 in patients with menkes Kinky Hair disease: immunohistochemical study.
Yonago acta medica, 2014Co-Authors: Atsushi Yokoyama, Asao Hirano, Masayuki Shintaku, Kousaku Ohno, Masako Kato, Kazuhiko Hayashi, Shinsuke KatoAbstract:Background To clarify the pathogenesis of cerebellar Purkinje cell death in patients with Menkes Kinky Hair disease (MD), a disorder of copper absorption, we investigated the morphological and functional abnormalities of residual Purkinje cells in MD patients and the mechanism of cell death. Methods Seven MD patients and 39 neurologically normal autopsy cases were studied. We performed histopathological and quantitative analyses of the Purkinje cells. In addition, we used immunohistochemistry to detect copper-dependent enzymes [cytosolic Cu/Znsuperoxide dismutase (SOD1) and copper chaperone for superoxide dismutase (CCS)], oxidative stress markers [4-hydroxy-2-nonenal (HNE) and acrolein] and heat shock protein (hsp) 32. Results The surviving MD Purkinje cells showed abnormal development, such as somatic sprouts and heterotopic location. Due to maldevelopment and degeneration, dendrites showed the cactus and weeping willow patterns. Axonal degeneration led to the formation of torpedoes. Quantitative analysis revealed loss of approximately 50% of the Purkinje cells in MD patients. Almost all of the normal Purkinje cells were positive for immunostaining by anti-CCS and anti-SOD1 antibodies, with staining of the cell bodies, dendrites and axons. Normal Purkinje cells were not stained by antibodies for HNE, acrolein or hsp 32. In MD patients, the majority of Purkinje cells were positive for CCS, but the positive rate for SOD1 was only about 23%. Approximately 56%, 42% and 40% of the Purkinje cells of MD patients were positive for HNE, acrolein and hsp 32, respectively. Conclusion In MD patients, about 50% of the Purkinje cells have been lost due to maldevelopment and degeneration. In the residual Purkinje cells, CCS expression seems to be nearly normal as a protective response to decreased SOD1 activity due to copper deficiency. Be cause oxidative stress is elevated secondary to decreased SOD1 activity, hsp 32 is induced as another protective mechanism.
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Immunohistochemical detection of products of lipid peroxidation and protein glycation in the cerebellum of Menkes' Kinky Hair disease patients
International Congress Series, 2002Co-Authors: Noriyuki Shibata, Asao Hirano, Koji Uchida, Ryoji Nagai, Seikoh Horiuchi, Satoshi Yamada, Tatsuo Sawada, Makio KobayashiAbstract:Abstract Menkes' Kinky Hair disease (MKHD) is a hereditary Cu malabsorption disorder characterized by Hair abnormalities, mental retardation and hypotonia. We previously suggested that Cu depletion induces oxidative stress generation in the cerebellum affected with this disease. To test oxidative damage involvement in MKHD, we analyzed immunohistochemical localization of products of lipid peroxidation and protein glycation in the cerebellum of five MKHD patients and five age-matched controls. Immunoreactivities for these examined products were undetectable in the control cases, and were localized in Purkinje cells, glial cells and endothelial cells of the MKHD patients. Our results indicate a certain implication for both lipid peroxidation and protein glycoxidation in MKHD.
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Cerebellar superoxide dismutase expression in Menkes' Kinky Hair disease: an immunohistochemical investigation.
Acta neuropathologica, 1995Co-Authors: Noriyuki Shibata, Asao Hirano, Makio Kobayashi, Takahiko Umahara, Toru Kawanami, Kohtaro AsayamaAbstract:This comparative immunohistochemical study deals with the expression of the cytosolic Cu/Zn-binding and mitochondrial Mn-dependent superoxide dismutases (SODs) in the cerebella of five patients with Menkes' Kinky Hair disease (MKHD) and five age-matched controls. Several cell types, including Purkinje cells and reactive astrocytes, of all MKHD patients examined were intensely stained by an antibody to Mn SOD, but not by an anti-Cu/Zn SOD antibody. By contrast, the cells of the five controls reacted very weakly or not at all with the anti-Mn SOD antibody, but were strongly reactive with the antibody to Cu/Zn SOD. These results suggest that the increased Mn SOD immunoreactivity in MKHD reflects enzyme induction as a protective mechanism against the highly toxic superoxide anion generated under the disease conditions.
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Cytochrome C oxidase deficiency and neuronal involvement in Menkes' Kinky Hair disease: immunohistochemical study.
Brain pathology (Zurich Switzerland), 1993Co-Authors: Marco Sparaco, Asao Hirano, Micho Hirano, Salvatore Dimauro, Eduardo BonillaAbstract:Antibodies against subunits II and IV of cytochrome c oxidase (COX) and against complex III of the respiratory chain were used to study the expression of these proteins in the cerebellum, spinal cord, and other regions of the central nervous system in an autoptic case of Menkes' Kinky Hair disease (MKHD). We found a reduced expression of COX subunits in all examined areas whereas staining for complex III appeared normal. Immunostaining was altered in morphologically well-preserved neurons, suggesting that COX deficiency may have a pathogenetic role in the neuronal degeneration of MKHD.
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Immunohistochemical Studies on Cerebellar Purkinje Cells of Patients with Menkes' Kinky Hair Disease
Neuropathology, 1993Co-Authors: Shinsuke Kato, Asao Hirano, Masayuki Ito, Eisaku Ohama, Katsuhiko Mikoshiba, Nobuaki Maeda, Shu‐hui ‐h Yen, Fritz Herz, Masayuki ShintakuAbstract:Immunohistochemical investigations were carried out on cerebellar Purkinje cells of eight patients with Menkes' Kinky Hair disease (MD) using an antibody against the inositol 1, 4, 5-triphosphate receptor which is identical to the cerebellar Purkinje cell glycoprotein P400 (P400/IP3R). In normal cerebellar Purkinje cells, the cell bodies, axons and dendrites including spiny branchlets were specifically stained by the antibody. By comparison, the immunoreactivity of the MD Purkinje cells ranged from negative to positive. The most frequent staining pattern in the MD Purkinje cells was that of cell bodies and proximal portions of the dendrites expressing P400/IP3R in varying degrees, with the peripheral dendrites including spiny branchlets not being stained. The Purkinje cells of the eight patients were also analyzed for expression of phosphorylated neurofilament proteins (pNFP), αB-crystallin, stress-response protein (srp) 72, srp 27 and ubiquitin. Most MD Purkinje cell bodies reacted with the antibody against pNFP. Although the proportion of stained Purkinje cells was less, a positive reaction was also observed with the antibodies to αB-crystallin, srp 72 and srp 27. By contrast, no normal Purkinje cell was stained by these antibodies. Our results suggest that the function of P400/IP3R in the Purkinje cells of MD patients is impaired, that these cells have an aberrant phosphorylation of NFP and that some of the imparied Purkinje cells synthesize specific sets of stress-related proteins.
Hilda Laufer - One of the best experts on this subject based on the ideXlab platform.
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Menkes Kinky Hair Disease with ‘Ragged Red’ Fibers
Developmental medicine and child neurology, 2008Co-Authors: Susan Morgello, Hart De C. Peterson, Leonard J. Kahn, Hilda LauferAbstract:ummary A 30-month-old infant with Menkes Kinky-Hair disease died, with prominent vascular, cerebral and cerebellar degeneration. Increased numbers of mitochondria containing homogeneous dense bodies were seen on electron–microscopic: examination of Purkinje cells. Subsarcolemmal aggregates of mitochondria (‘ragged red’ fibers) were present in skeletal muscle. These mitochondrial alterations support the hypothesis that copper deficiency results in mitochondrial encephalomyopathy. RESUMEN Maladie des cheveux tordus de Menkes avec fibres ‘rouge guenilles’ Un nourrisson de 30 mois presentant une maladie de Menkes a cheveux tordus mourut, avec des signes massifs de degeneration vasculaire, cerebrale et cerebelleuse. Un nombre accru de mitochondries contenant des corps denses homogenes furent observees au microscope electronique a l'examen des cellules de Purkinje. Des agregats subsarcolemmiques de mitochondries (fibres ‘rouge guenilles’) etaient presents dans les muscles squelettiques. Ces alterations mitochondriales favorisent l'hypothese selon laquelle la deficience en cuivre aboutirait a une encephalomyelopathie mitochondriale. ZUSAMMENFASSUNG Menkes Kinky-Hair Syndrom mit ‘ragged red’ Fasern Ein 30 Monate altes Kind mit Menkes Kinky-Hair Syndrom starb, es hatte ausgepragte vaskulare, cerebrale und cerebellare Degenerationen. Bei der elektronenmikroskopischen Untersuchung der Purkinje Zellen fanden sich vermehrt Mitochondrien, die homogene, dichte Partikel enthielten. Im Skelettmuskel konnten Mitochondrienaggregate unter dem Sarkolemm (‘ragged red’ Fasern) nachgewiesen werden. Diese Mitochondrienveranderungen stutzen die Hypothese, das durch Kupfermangel eine mitochondriale Enzephalomyelopathie entsteht. RESUMEN Enfermnedad del pelo ensortijado de Menkes con fibras rojas en harapo Un nino de 30 meses de edad con enfermedad del pelo ensortijado de Menkes fallecio con una pronunciada degeneracion vascular cerebral y cerebelosa. En el examen con microscopio electronico de las celulas de Purkinje se vio un numero elevado de mitocondrias conteniendo cuerpos densos homogeneos. En el musculo esqueletico habia agregados subsarcolemicos de mitocondrias (fibras rojas en harapo) Esta alteraciones mitocondriales apoyan la hipotesis de que un deficit de cobre da lugar a una encefalopatia mitocondrial.
Hideo Kinebuchi - One of the best experts on this subject based on the ideXlab platform.
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Copper-induced toxicity in macular mutant mouse: An animal model for Menkes' Kinky-Hair disease
Toxicology and applied pharmacology, 1991Co-Authors: Noriyuki Shiraishi, Tetsuya Taguchi, Hideo KinebuchiAbstract:Abstract These studies were designed to determine if macular mutant mouse, which is a proposed animal model of Menkes' Kinky-Hair disease, is sensitive to the acute toxic effects of Cu as compared to normal and heterozygote mice. Single sc injection of Cu were administered to 6-to 8-day-old mice, and mortalities were recorded for 30 days. The copper treatment at high doses (12 to 25 mg Cu/kg) was very toxic to mutant mice as compared to normal mice, and almost all mutant mice died within 10 days after injection. The effect of Cu toxicity on heterozygote mice was intermediate. The LD50 values 3 days after injection of Cu were 29.5 mg Cu/kg for normal mice, 23.5 mg Cu/kg for heterozygote mice, and 15.5 mg Cu/kg for mutant mice. In Cu-injected mutant mice (11 and 18 mg Cu/kg), significant elevations in serum aspartate aminotransferase and lactate dehydrogenase activity occurred as compared to Cu-injected normal and heterozygote mice. However, no significant elevations in serum creatinine and urea nitrogen contents in Cu-injected mutant were observed as compared to normal and heterozygote mouse. No significant differences in heaptic metallothionein(MT) and MT-1 mRNA, and serum ceruloplasmin oxidase activity levels were observed between Cu-injected normal and mutant mouse. These results indicated that macular mutant mice was sensitive to the acute toxic or hepatotoxic effects of Cu as compared to normal and heterozygote mice.
Owen M. Rennert - One of the best experts on this subject based on the ideXlab platform.
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menkes Kinky Hair syndrome is it a treatable disorder
Clinical Genetics, 2008Co-Authors: Adolfo D. Garnica, Jaime L Frias, Owen M. RennertAbstract:A male infant with Menkes Kinky Hair Syndrome was treated with a 3-week course of cupric acetate infusions, which was terminated when he developed aminoaciduria. The lack of improvement seen in this infant is representative of the reported experience with parenteral copper therapy in this condition, and may be attributable to the presence of a clinically significant abnormality in copper metabolism in utero.
