M Hirano

..We further found that mutants were targeted for rapid proteasome-mediated degradation. These results help establish pathogenic and physiological protein characteristics of APTX in neuronal cells...

..The goal of this study was to prove the functional involvement of APTX in SSB repair (SSBR)...

..Our results provide important clinical information and prediction for r(20) syndrome...

..Our findings suggest that the clinical phenotypes are caused by a loss of aprataxin function, attributable largely to diminished HIT activity but partially to a reduction in the levels of gene products...

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..Thus, the alternative splicing increases the molecular diversity of aprataxin and the expression profiles of these transcripts in various tissues may be related to the tissue-specific phenotypes...

..Although concomitant diseases such as diabetes and chronic renal failure may lead to an aggressive course, all patients described in detail have had good outcomes...

..To our knowledge, this is the first study to show that the ACT-AA genotype is a risk factor and modulating factor for MSA. Our findings suggest the involvement of ACT-relating inflammatory process in the pathogenesis of MSA...

..Our data suggest that the polymorphic region of the VMAT2 gene studied here is not closely related to PD...

..Although the details remain uncertain, our results suggest that ASK1 is potentially involved in pathogenesis of DRPLA and that HN might contribute partially to the suppression of neurodegeneration in polyQ diseases...

..Our results suggest that reduction of VMAT2 activity might attenuate the efficacy of L-DOPA therapy for patients with PD...

..We thus propose that HN, which increases cellular ATP levels without inducing mtDNA replication, may be suited for the treatment of MELAS...

..In these diseases increased risk of sudden cardiac arrest is established, while that in ALS remains uncertain...

..This novel feature of HN may enable us to apply this peptide for the management of diseases involving poor metabolic activity, such as mitochondria-related disorders and brain ischemia...

..Recent studies suggest that SAs in PD may be related to impairment of hypothalamic orexin neurons, similar to narcolepsy. Whether orexin is associated with long-term activation of dopaminergic receptors remains uncertain...

..These observations suggested that direct and/or indirect bilateral involvement of the DM might be associated with odor abnormalities in patients with thalamic infarction...

..Co-expression analysis showed that mutant enzyme (GCH-G90V) inactivated the normal enzyme in the COS cells. Similarly, GCH-G203R showed the dominant negative effects. These results supported our proposed hypothesis...

..Thus, histogram and ROI analyses complement each other and may permit the sensitive, quantitative evaluation of neurodegeneration in DRPLA, especially that involving the globus pallidus showing normal T2 signals...

..These findings may help develop treatments for currently intractable triple A syndrome and other oxidative-stress-related neurological diseases, and contribute to nuclear compartmentalization study...

..A further binding study showed reduction of the D3R binding sites in PD lymphocytes. The decrease of the D3R mRNA expression correlated with the degree of clinical severity in PD patients...

..The present study could be relevant to understanding the molecular mechanisms of opioids in a state of drug tolerance or dependence, and in patients under anesthesia or being treated for pain...

..Decreased nuclear APTX increased oxidative stress-induced DNA damage and cell death. Phosphorylation-resistant APTX, kinase inhibitors, and antioxidants may be therapeutic options for SCA14...

..Since TFIIH is a repair/transcription factor, TTD-specific alterations of TFIIH possibly result in transcriptional defects, which might be implication for the lack of increased incidence of skin cancers in TTD patients...

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..Although our study showed mild neuroprotective effects, further structural modification of compounds that retain this residue may decrease cytotoxicity and increase protective activity against polyQ toxicity...

..Consequent DNA damage, beyond the limited capacity of DNA repair proteins, i.e., APTX and ligase I, may participate in triggering cell death...

..Collectively, we propose that naturally- and experimentally-induced exon skipping at least partly restores the mutant Parkin gene deficit, providing a molecular basis for the development of therapeutic exon skipping...

..There were no adverse reactions. We conclude that selective 5-HT4 agonist therapy is beneficial for patients with PD who have RFs...

..In the present study, the GTP-CH-I gene and the clinical features of eight HPD/DRD patients from six families were analysed to determine the correlations between clinical expression and the mutations in the GTP-CH-I gene...

..From these in vivo and in vitro findings, we propose that HN expression might be induced in response to the energy crisis within affected fibers and vessels in MELAS muscles and further be a possible therapeutic candidate for MELAS...

..This study accessed the feasibility of using tractography-based analysis to evaluate the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) of three cerebellar peduncles in subtypes of spinocerebellar degenerative disease...

..Although confirmation must await future larger-scale SPECT and functional studies, our findings suggest that SPECT can be used to non-invasively monitor in vivo cortical function in this disease...

..Collectively, our findings suggest that HN may be specifically expressed in response to defects in energy production in muscles with mitochondrial abnormalities...

..CONCLUSIONS: MRS may sensitively and specifically detect biochemical alterations in susceptible regions of patients with adult-onset DRPLA...

..The chronological relationship between the signal changes and the clinical deterioration suggested that the epilepsy, at least in part, contributed to the progression of white matter degeneration, the hallmark of DRPLA...

..He had a mobile mural thrombus at the VA occlusion site on head rotation. Surgical treatment may effectively prevent recurrences...

..The interferon beta-1b therapy then provided a clinical benefit. Hopefully this report will allow MS patients in similar situations to make more rapid, unprejudiced judgments than our patients...