Biomedical subjects

Hidetaka Yano

Publications and source records attributed to Hidetaka Yano.

7 recordsLinked to original sources

PubMed2004

Mutations of the MTHFR gene (428C>T and [458G>T+459C>T]) markedly decrease MTHFR enzyme activity.

Methylenetetrahydrofolate reductase (MTHFR) is the only route for the synthesis of 5-methyltetrahydrofolate, which is utilized to convert homocysteine to methionine. In this study, we measured the enzyme activity of a mutant MTHFR that was detected in a patient with hyperhomocysteinemia. The 428C>T mutation in exon 2 of the MTHFR gene is a novel mutation, while the [458G>T+459C>T] mutation in exon 2 is a previously reported mutation. The activity of mutant enzymes containing the 428C>T, [458G>T+459C>T] and 677C>T mutations was 12.7+/-4.7%, 48.1+/-18.8%, and 43.6+/-14.4%, respectively, of that of the wild type enzyme. Our results suggest that these two variants each result in a severe MTHFR deficiency, which causes a developmental delay and cerebral vascular disease.

Adolescent↗

PubMed2004

The regulatory region polymorphisms of the MTHFR gene are not associated with Alzheimer's disease.

Recent epidemiological studies have emphasized the impact of elevated blood homocysteine levels on the pathogenesis of Alzheimer's disease (AD). In spite of a significant impact of a MTHFR C677T polymorphism on the blood homocysteine levels, the association between the C677T polymorphism and AD remains controversial. Therefore, other unidentified genetic factor(s) that regulate blood homocysteine levels may exist. Here, we have analyzed the 5'-upstream region of the MTHFR gene and examined AD patients (n = 223) and nondemented individuals (n = 323) for polymorphisms in the 5'-upstream region of the MTHFR gene. We identified two polymorphisms (-713G/A and -393C/A, upstream of the start codon). We found no significant relationship between AD and the 5'-upstream region polymorphisms of the MTHFR gene. Thus, our study does not reinforce the hypothesis of an independent involvement of the MTHFR gene upstream region polymorphisms in AD risk.

Aged↗

PubMed2004

p53-mediated mitochondrial dysfunction by proteasome inhibition in dopaminergic SH-SY5Y cells.

Decreased proteasome activity is an important pathology in Parkinson's disease (PD), which is related to cell death and Lewy body formation. In this study, we show that p53-activity may correlate with neuronal death via the mitochondrial pathway in PD model. The proteasome inhibitor, MG132, induced the accumulation of p53 in human dopaminergic neuroblastoma SH-SY5Y cells. The increased stabilization of p53 upregulated the level of Bax and mitochondrial depolarization. These events were inhibited by the p53 inhibitor, pifithrin-alpha (PFT). Cell viability analyzes demonstrated that PFT partially prevented MG132-induced cell death. These results suggest that p53 is a candidate as an intermediary between the proteasome system and mitochondria-related neuronal death in PD.

Benzimidazoles↗

PubMed2004

A haplotype of the methylenetetrahydrofolate reductase gene is protective against late-onset Alzheimer's disease.

Epidemiological studies have shown that elevated plasma homocysteine (Hcy) levels play an important role in the pathogenesis of Alzheimer's disease (AD). In spite of the evidence that a C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene elevates plasma Hcy levels, the impact of the C677T polymorphism on the development of AD is controversial. Here, we performed a genetic case-control study in a Japanese population to investigate whether three polymorphisms of the MTHFR gene, C677T (Ala222Val), A1298C (Glu429Ala), and A1793G (Arg594Gln), are associated with the development of late-onset AD (LOAD). In our study, the MTHFR gene had four major regional haplotypes: Haplotype A (677C-1298A-1793G), Haplotype B (677T-1298A-1793G), Haplotype C (677C-1298C-1793G), and Haplotype D (677C-1298C-1793A). The frequency of Haplotype C in LOAD was significantly lower than that in control group. Furthermore, the benefit conferred by the presence of at least one Haplotype C was stronger in LOAD patients who lacked the ApoE 4 allele (OR=0.293; 95% CI=0.115-0.744; P=0.010). The results indicate that Haplotype C of the MTHFR gene is protective against the development of LOAD.

Aged↗

PubMed2003

PI3K is a key molecule in the Nrf2-mediated regulation of antioxidative proteins by hemin in human neuroblastoma cells.

Oxidative stress and ferrous metabolism are important in the pathogenesis in Parkinson's disease. In dopaminergic neurons, several stress proteins are upregulated under oxidative stress. To clarify this mechanism, we investigated hemin-related signal transduction and the induction of oxidative stress-related proteins in SH-SY5Y cells. We identified phosphatidylinositol 3-kinase (PI3K) and Nrf2 as important molecules in the induction of heme oxygenase-1, thioredoxin, and peroxiredoxin-I. PI3K-related signal controlled Nrf2 activation, and consequently, PI3K inhibitors blocked the nuclear translocation of Nrf2 and induction of stress proteins. These observations suggest that PI3K and Nrf2 are key molecules in maintaining suitable conditions under oxidative stress and ferrous metabolism.

DNA-Binding Proteins↗

PubMed2003

[A case report of syphilitic meningitis with right oculomotor nerve palsy].

A 63-year-old man presented with acute-onset right ptosis and diplopia. The patient reported having engaged in unspecified sexual activities during his third decade and was found to have positive syphilitic serological findings at the age of 56 years. No clinical symptoms were noted at this time. On admission, he showed only right oculomotor nerve palsy. The patient's intelligence, gait and sensory functions were normal. Laboratory analysis revealed positive syphilitic serological findings and examination of the cerebrospinal fluid (CSF) further revealed pleocytosis, a higher IgG index and positive syphilitic reactions. A computed tomographic scan and other imaging studies were diagnostically nonspecific. We made a diagnosis of right oculomotor nerve palsy due to syphilitic meningitis. We treated the syphilitic meningitis with intravenous injections of penicillin G (24 million units per day for 21 days). Jarisch-Herxheimer reaction and other side effects were not apparent. We first made a thorough examination of the CSF to rule out diagnosis of meningitis, and pursued methylprednisolone pulse therapy (MPP, 1 g/day for 3 days) to treat the oculomotor nerve palsy. The ptosis and diplopia showed signs of improvement following the second MPP therapy session. The present case suggests that neurosyphilis is an important differential diagnosis for presentations of unspecific oculomotor nerve palsy and that MPP therapy may prove an effective treatment for it, even where there has been the long clinical onset.

Humans↗

PubMed2003

[A case of acute cholinergic adverse effects induced by donepezil overdose: a follow-up of clinical course and plasma concentration of donepezil].

A 79-year-old woman with Alzheimer's disease was admitted due to acute cholinergic symptoms induced by overdose (45 mg) of donepezil (DPZ). Physical examination showed bradycardia, sinus arrhythmia, vomiting and respiratory insufficiency. She was treated with atropine intravenously and her cholinergic symptoms subsided in the next evening. After 5 days she was discharged from the hospital and DPZ was withholded for about 4 weeks. The plasma concentration of DPZ was 54.6 ng/ml on admission and gradually decreased to the normal limits in about 90 hours. The calculative half-life of DPZ was about 55 hours. Since the half-life of DPZ is long and differs between individuals, hospitalization and treatment with atropine is recommended for cholinergic side effects induced by overdose of DPZ. It is important to prevent dosing errors in cooperation with medical providers, patients and families.

Aged↗