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Kenichi Sato

Publications and source records attributed to Kenichi Sato.

At least 19 recordsLinked to original sources
PubMed2006

De novo and salvage pathways of DNA synthesis in primary cultured neurall stem cells.

We studied the de novo and salvage pathways of DNA synthesis in sphere-forming neural stem cells obtained from mouse embryos by a neurosphere method. The former pathway needs folic acid (FA) for nucleotide biosynthesis, while the latter requires deoxyribonucleosides (dNS). We examined the proliferative activity of sphere-forming cells in E14.5 embryos by counting the number of spheres formed in media that lacked FA and/or dNS. Proliferation failure and apoptosis occurred in a deficient medium lacking of both FA and dNS. Spheres formed in the deficient medium supplemented with dNS, without FA, did not produce neuron, but rather only seem to generate astrocytes and oligodendrocytes when plated under differentiation condition in culture. On the other hand, a subpopulation of cultured cells formed spheres in the deficient medium supplemented with FA alone in an appropriate concentration, and did possess the self-renewing and multipotential characteristics of neural stem cells. Spheres formed in the media containing low dose Azathioprine and methotrexate, inhibitors of de novo DNA synthesis, were selectively prevented from producing neurons even in the presence of FA. These results suggested that activating de novo DNA synthesis was needed for neural stem cells to proliferate with multipotentiality.

Age Factors↗
PubMed2006

Clinical heterogeneity of alpha-synuclein gene duplication in Parkinson's disease.

OBJECTIVE: Recently, genomic multiplications of alpha-synuclein gene (SNCA) have been reported to cause hereditary early-onset parkinsonism. The objective of this study was to assess the frequency of SNCA multiplications among autosomal dominant hereditary Parkinson's disease (ADPD). METHODS: We screened 113 ADPD probands and 200 sporadic PD cases by quantitative polymerase chain reaction and confirmed SNCA multiplications by fluorescence in situ hybridization (FISH) and comparative genomic hybridization array. RESULTS: Two families (two patients from Family A and one from Family B) with SNCA duplication were identified among ADPD patients. Even though they had the same SNCA duplication, one patient had dementia. Because there was exactly the same difference between the regions originated from each patient, the finding suggests that the phenotype of SNCA multiplication may be also influenced by the range of duplication region. We also detected asymptomatic carriers in the families of both patients. Interestingly, the penetrance ratio was 33.3% (2/6) in one kindred, indicating that the ratio was very much lower than expected. INTERPRETATION: These two newly identified Japanese patients with SNCA duplication and the five previously identified American and European families with SNCA triplication or duplication mutations indicate that the incidence of SNCA multiplication may be more frequent than previously estimated.

Aged↗
PubMed2006

Clinicogenetic study of mutations in LRRK2 exon 41 in Parkinson's disease patients from 18 countries.

We screened LRRK2 mutations in exon 41 in 904 parkin-negative Parkinson's disease (PD) patients (868 probands) from 18 countries across 5 continents. We found three heterozygous missense (novel I2012T, G2019S, and I2020T) mutations in LRRK2 exon 41. We identified 11 (1.3%) among 868 PD probands, including 2 sporadic cases and 8 (6.2%) of 130 autosomal dominant PD families. The LRRK2 mutations in exon 41 exhibited relatively common and worldwide distribution. Among the three mutations in exon 41, it has been reported that Caucasian patients with G2019S mutation have a single-founder effect. In the present study, Japanese patients with G2019S were unlikely to have a single founder from the Caucasian patients. In contrast, I2020T mutation has a single-founder effect in Japanese patients. Clinically, patients with LRRK2 mutations had typical idiopathic PD. Notably, several patients developed dementia and psychosis, and one with I2020T had low cardiac (123)I-metaiodobenzylguanidine (MIBG) heart/mediastinum ratio, although the ratio was not low in other patients with I2020T or G2019S. Clinical phenotypes including psychosis, dementia, and MIBG ratios are also heterogeneous, similar to neuropathology, in PD associated with LRRK2 mutations.

Antiparkinson Agents↗
PubMed2006

Prognosis of Parkinson's disease: time to stage III, IV, V, and to motor fluctuations.

We report a long-term outcome on a large cohort of Japanese patients with Parkinson's disease (PD). A total of 1,768 (793 men, 975 women) consecutive patients visited our clinic from 1 January 1989 to 31 December 2002. Among them, 1,183 patients (531 men, 652 women) came to our clinic within 5 years from the onset of disease and at the Hoehn & Yahr Stage III or less at the first visit. Long-term outcome was evaluated in this subcohort of the patients. We examined the duration to reach Stage III, IV, and V, and the duration to develop wearing off and dyskinesia. Time to reach Stage III was slightly but significantly shorter in women, in that 23.8% of men and 35.3% of women reached Stage III by the end of the 5th year; 49.7% of men and 63.3% of women reached Stage III by the end of the 10th year, and 88.9% of men and 79.9% of women by the end of the 15th year (P < 0.001). Also, durations to develop wearing off and dyskinesia were shorter in women compared to men. These data suggest that the disease progression may be slightly faster for women. Young-onset patients showed significantly longer duration to reach Stage III, IV, and V but shorter duration to develop wearing off and dyskinesia. Not many studies are available in the literature on the long-term outcome of PD, and our data would be useful as a reference.

Adult↗
PubMed2006

Assisting the diagnosis of thyroid diseases with Bayesian-type and SOM-type neural networks making use of routine test data.

Patients with hyperthyroidism sometimes take much time to receive the final diagnosis. To improve patient QOL, simple screening for hyperthyroidism by thyroid non-specialists at the physical check-up is highly expected. Therefore, we applied both Bayesian-type and SOM-type neural networks since we assured the approach useful in analysing thyroid function diagnosis in the previous work. Routine test (14 parameters) data from 66 subjects with a known diagnosis (18 patients with hyperthyroidism and 48 healthy volunteers) were adopted as learning data, and then 142 individuals who also received the same routine tests at the Tohoku University Hospital were screened to predict patients with hyperthyroidism. Both neural networks using 14 parameters predicted several patients as having hyperthyroidism with high probability, including all three hyperthyroid patients diagnosed later by the physician. Further detailed analysis of the routine test parameters that were important for classification found that screening with a set of three parameters (alkaline phosphatase, serum creatinine and total cholesterol) or plus aspartate aminotransferase allowed for quite accurate screening. These results showed that the same neural networks as previous work allows simple screening of patients for hyperthyroidism on the basis of routine test data, and that physicians not specializing in the thyroid can rapidly identify individuals suspected of having hyperthyroidism, to permit a rapid referral for examination and treatment by thyroid specialists.

Bayes Theorem↗
PubMed2006

[A 62-year-old woman with early-onset Parkinson's disease associated with the PINKi gene deletion].

We report the first case of early-onset Parkinson's disease (EOP) with the PTEN-induced kinase 1 (PINK1) gene deletion in 62 years old Japanese female. The symptoms were started with unstable gait at the age 38. Parkinsonian symptoms became apparent in 45 years old. L-Dopa was markedly effective on her parkinsonian symptoms. However, equinovarus foot induced by L-Dopa intake appeared three months prior to the admission. On admission, she presented with mild cognitive impairment, severe depression, marked retropulsion, resting tremor in the left upper limb and mild hyperreflexia in the four limbs. Rigidity was not present. Mutational analysis revealed homozygous deletion from exon 6 to 8 in the PINK1 gene. An ethnic diversity in PINK1 mutation is suggested.

Age Factors↗
PubMed2005

A single nucleotide substitution that abolishes the initiator methionine codon of the GLDC gene is prevalent among patients with glycine encephalopathy in Jerusalem.

Glycine encephalopathy (GE) (non-ketotic hyperglycinemia) is an autosomal recessive neurometabolic disease caused by defective activity of the glycine cleavage system. Clinically, patients present usually in the neonatal period with hypotonia, encephalopathy, hiccups and breath arrests with or without overt seizures. GE is considered rare, but its incidence is relatively high in several geographical areas around the world. We report a novel mutation causing GE in six extended Arab families, all from a small suburban village (population 5,000). A methionine to threonine change in the initiation codon of the glycine decarboxylase gene led to markedly reduced glycine decarboxylase mRNA levels and abolished glycine cleavage system activity.

Amino Acid Oxidoreductases↗
PubMed2005

Selective chemical vapor deposition synthesis of double-wall carbon nanotubes on mesoporous silica.

Double-wall carbon nanotubes (DWNTs) have been selectively synthesized over Fe/Co loaded mesoporous silica by catalytic chemical vapor deposition of alcohol. Several silica materials with desired pore diameter and morphology have been investigated for the DWNT growth. The diameter distribution and selectivity of the DWNT are found to depend on the reaction temperature, pore size, and thermal stability of the support material. A high-yield synthesis of DWNTs has been achieved at 900 degrees C over high-temperature stable mesoporous silica. The outer diameter of DWNTs is found to be in the range of 1.5-5.4 nm with a "d" spacing of 0.38 +/- 0.02 nm between inner and outer layers, which is much larger than those of multiwall carbon nanotubes.

Alcohols↗
PubMed2005

In vitro antibacterial activity of DX-619, a novel des-fluoro(6) quinolone.

The in vitro activities of DX-619, des-fluoro(6) quinolone, against 1,208 clinical isolates were examined. DX-619 was particularly potent against staphylococci, including ciprofloxacin- and methicillin-resistant strains; the MIC at which 90% of the strains tested were inhibited was 0.5 microg/ml. In addition, DX-619 was also active against gram-negative bacteria.

Anti-Infective Agents↗
PubMed2005

An analysis of thyroid function diagnosis using Bayesian-type and SOM-type neural networks.

Thyroid function diagnosis is an important classification problem, and we made reanalysis of the human thyroid data, which had been analyzed by the multivariate analysis, by the two notable neural networks. One is the self-organizing map approach which clusters the patients and displays visually a characteristic of the distribution according to laboratory tests. We found that self-organizing map (SOM) consists of three well separated clusters corresponding to hyperthyroid, hypothyroid and normal, and more detailed information for patients is obtained from the position in the map. Besides, the missing value SOM which we had introduced to investigate QSAR problem turned out to be also useful in treating such classification problem. We estimated the classification rates of thyroid disease using Bayesian regularized neural network (BRNN) and found that its prediction accuracy is better than multivariate analysis. Automatic relevance determination (ARD) method of BRNN was surely verified to be effective by the direct calculation of classification rates using BRNN without ARD for all possible combinations of laboratory tests.

Bayes Theorem↗
PubMed2004

Persistent NKH with transient or absent symptoms and a homozygous GLDC mutation.

Three of four nonketotic hyperglycinemia patients homozygous for a novel GLDC mutation (A802V) were treated by assisted respiration and/or sodium benzoate with or without ketamine and had transient neonatal or absent symptoms and normal developmental outcome, despite persisting biochemical evidence of nonketotic hyperglycinemia. This exceptional outcome may be related to the high residual activity of the mutant protein (32% of wild type) and therapeutic intervention during a critical period of heightened brain exposure and sensitivity to glycine.

Adult↗
PubMed2004

Novel PINK1 mutations in early-onset parkinsonism.

PINK1 was recently found to be associated with PARK6 as the causative gene. We performed mutation analysis in eight inbred families whose haplotypes link to the PARK6 region. We identified six pathogenic mutations (R246X, H271Q, E417G, L347P, and Q239X/R492X) in six unrelated families. All sites of mutations were novel, suggesting that PINK1 may be the second most common causative gene next to parkin in parkinsonism with the recessive mode of inheritance.

Adolescent↗
PubMed2004

Mild variant of nonketotic hyperglycinemia with typical neonatal presentations: mutational and in vitro expression analyses in two patients.

In neonatal-onset nonketotic hyperglycinemia, severe psychomotor retardation is the expected uniform outcome. We report two patients with typical neonatal presentation who showed far better developmental outcomes. The in vitro expression analysis of the identified GLDC mutations revealed considerable residual enzyme activity, suggesting prognostic and enzymatic heterogeneity even in neonatal-onset nonketotic hyperglycinemia.

Amino Acid Oxidoreductases↗
PubMed2004

Genetic testing of glycogen storage disease type Ib in Japan: five novel G6PT1 mutations and a rapid detection method for a prevalent mutation W118R.

We devised a simple method using a TaqMan fluorogenic probe for detection of a prevalent G6PT1 mutation W118R among Japanese patients with glycogen storage disease type Ib. The W118R mutation was detected in three of six newly diagnosed Japanese patients. The W118R-negative alleles were screened for causative mutations by sequencing analysis, revealing five novel mutations. The genetic tests using the simple TaqMan method coupled with sequencing analysis would facilitate the early diagnosis of this disorder.

Adult↗
PubMed2004

Application of a self-organizing map to quantitative structure-activity relationship analysis of carboquinone and benzodiazepine.

Self-organizing map (SOM) of Kohonen seems to be a promising approach beyond the standard one to regression for some classification problems encountered in the field of pharmacy. We apply them, therefore, to the quantitative structure-activity relationship (QSAR) in carboquinones and benzodiazepines, and show their usefulness. Most QSAR analysis using neural networks has been made by adopting neural networks with supervised learning. On the contrary, SOM obeys unsupervised learning and originally does not involve the use of desired target data. If we note that an appreciable fraction of data may be missing without making the similarity comparison impossible in SOM if the number of attributes considered is appreciable, QSAR analysis using SOM is found to be possible as if supervised learning. Similar to target data in supervised learning, we can take into account target data (=observed activity) as one of attributes in addition to other attributes (=structural descriptors). Choice of optimal descriptors as input parameters was found to be essential to generate valuable SOM.

Benzodiazepines↗
PubMed2004

[Significance of serum oxidative stress related markers and genotype of GST gene in the pathogeneses of primary biliary cirrhosis].

The studies using an immunohistological technique revealed that overexpression of oxidative stress-related substance such as HNE was observed in the liver of primary biliary cirrhosis patients. These data suggested that oxidative stress participated in the pathogenesis of primary biliary cirrhosis. Therefore we analyzed serum oxdative stress marker (8-OHdG) and anti oxidative substances (Mn-SOD and TRX) to evaluate their clinical significance. In addition we analyzed the genotype of anti oxidative substance GST that has been reported to relate susceptibility of autoimmune disease. Serum levels of 8-OHdG, Mn-SOD and TRX in PBC patients were significantly higher than those of healthy subjects (P<0.001). Though there was no relation between serum level of 8-OHdG and clinical data, positive correlation between serum level of Mn-SOD, TRX and serum level of ALP, IgM was observed. Positive correlation was also observed between serum level of Mn-SOD and TRX. Serum levels of Mn-SOD of patients who responded to UDCA therapy were significantly higher than those of patients who did not response to therapy (P<0.01). Although genotypic difference of GSTM1 and GSTT1 by peripheral blood mononuclear cells did not relate to susceptibility of PBC, serum titer of AMA of GSTM1 null and GSTT1 null patients were significantly higher than those of GSTM1 positive and/or GSTT1 positive patients (P< 0.05). These findings suggest that serum oxidative stress-related markers may reflect the extent of liver damage of PBC, and may relate to the efficacy of UDCA therapy on PBC. It also made clear that genotype of GST related to the titer of AMA.

8-Hydroxy-2'-Deoxyguanosine↗