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Takashi Yoshimoto

Publications and source records attributed to Takashi Yoshimoto.

At least 19 recordsLinked to original sources
PubMed2006

Population data of six STR loci using hexaplex PCR amplification and typing system, "Midi-6" in four regional populations in Japan.

The genetic differences of the allele frequency distributions for six STR loci (D20S480, D6S2439, D6S1056, D9S1118, D4S2639, and D17S1290) among regions in Japan were examined using our recently designed hexaplex amplification and typing system, "Midi-6" newly named, to construct a database in the Japanese population. Genotypes at six loci were analyzed in 198, 200, 175, and 196 individuals from the area of Akita, Nagoya, Oita, and Okinawa, respectively, in Japan. The allele frequency distributions were significantly different (p<0.05) at from one to five loci among the four populations when compared pairwise. Significant differences were also observed at two or three loci between Oita- or Okinawa-Japanese and the "pooled" population (n=769), respectively. However, since F(ST) (theta) values were extremely low (<0.05), ranging from 0.0020 to 0.0118 for six loci, genetic differentiation within the pooled Japanese population was negligible. Therefore, it suggested that the data of the allele frequencies at six loci in the pooled population would be employed as the base of calculation for statistical probabilities.

DNA Fingerprinting↗
PubMed2006

Correlation between copper/zinc superoxide dismutase and the proliferation of neural stem cells in aging and following focal cerebral ischemia.

OBJECT: Neural stem cells (NSCs) have been demonstrated in the subventricular zone (SVZ) of the lateral ventricle and the subgranular zone of the hippocampal dentate gyrus (DG). Although aging rats manifest a decrease in NSCs, rats exposed to stress (for example, ischemia, epilepsy, radiation, and trauma) show an increase in these cells. In transgenic mice, the overexpression of human copper/zinc superoxide dismutase (SOD1), an endogenous antioxidant, has been reported to be a protective enzyme against transient focal cerebral ischemia. The authors investigated the correlation between SOD1 and the proliferation of NSCs in aging as chronic oxidative stress (Experiment 1) and acute oxidative stress induced by transient focal cerebral ischemia (Experiment 2) in mice. METHODS: Bromodeoxyuridine (BrdU) was used in the evaluation of NSCs. In Experiment 1, NSCs in the SVZ significantly increased in 16-month-old transgenic mice compared with wild-type mice (p = 0.0001). In Experiment 2, mice were subjected to 30-minute occlusions of the middle cerebral artery. The increase in NSCs in the DG in transgenic mice was significantly greater than that in wild-type mice (p < 0.05). CONCLUSIONS: Results in this study suggest that chronic and acute oxidative stress may inhibit the proliferation of NSCs and that SOD1 may play a key role in NSC proliferation.

Aging↗
PubMed2005

Phylogenetic relationship of the populations within and around Japan using 105 short tandem repeat polymorphic loci.

We have analyzed 105 autosomal polymorphic short tandem repeat (STR) loci for nine East and South-eastern Asian populations (two Japanese, five Han Chinese, Thai, and Burmese populations) and a Caucasian population using a multiplex PCR typing system. All the STR loci are genomewide tetranucleotide repeat markers of which the total number of observed alleles and the observed heterozygosity were 756 and 0.743, respectively, for Japanese populations. Phylogenetic analysis for these allele frequency data suggested that the Japanese populations are more closely related with southern Chinese populations than central and/or northern ones. STRUCTURE program analysis revealed the almost clearly divided and accountable population structure at K=2-6, that the two Japanese populations always formed one group separated from the other populations and never belong to different groups at K> or =3. Furthermore, our new allele frequency data for 91 loci were analyzed with those for 52 worldwide populations published by previous studies. Phylogenetic and multidimensional scaling (MDS) analyses indicated that Asian populations with large population size (six Han Chinese, three Japanese, two Southeast Asia) formed one distinct cluster and are closer to each other than other ethnic minorities in east and Southeast Asia. This pattern may be the caviar of comparing populations with greatly differing population sizes when STR loci were analyzed.

Asia, Southeastern↗
PubMed2005

The relationship among p53 oligomer formation, structure and transcriptional activity using a comprehensive missense mutation library.

Tumor suppressor p53 forms a homo-tetramer through its COOH-terminal oligomerization domain and acts as a sequence-specific transcription factor. We have analysed the interrelation among the transcriptional activities, the structure and the cancer-related mutations in the oligomerization domain by using a comprehensive missense mutation library. Here, we examined the ability of 184 mutant p53s in the domain to form an oligomer by expressing these mutant p53s in yeast, and compared the data with the previous information. We showed that specific residues in the alpha-helix and the beta-strand of the oligomerization domain were critical for both oligomer formation and sequence-specific transactivation, and the activities were closely related. In particular, the alpha-helix was more sensitive to amino-acid substitutions than the beta-strand. We found identity in the interrelation between the two activities, that is, monomer mutants were transcriptionally inactive whereas dimer and tetramer mutants retained their transcriptional activities. In TP53 mutation databases, a small number of mutations have been reported in this domain. Surprisingly, most do not encode p53s defective in functional properties. These results indicate that, although oligomer formation is essential for p53 transactivation function, the inactivation of oligomer formation and therefore the inactivation of transactivation may not be essential for tumor suppression by p53 because they do not lead to oncogenic proteins.

Biopolymers↗
PubMed2005

Novel magnetic resonance angiography stage grading for moyamoya disease.

BACKGROUND: Magnetic resonance angiography (MRA) has been acknowledged as a noninvasive diagnostic modality for moyamoya disease. However, in terms of staging of moyamoya disease, conventional angiography is still the gold standard. Therefore, the purpose of this study was to establish MRA grades for moyamoya disease as an alternative to conventional angiography. METHODS: Twenty-two patients (44 sides) with moyamoya disease diagnosed by conventional angiography were evaluated by MRA during the past 5 years. MRA scores were assigned based on the severity of occlusive changes of the internal carotid artery, the horizontal portion of the middle cerebral artery, the anterior and the posterior cerebral arteries and the signals of the distal branches of these arteries. Total points ranged from 0 (normal) to 10 (most severe). RESULTS: MRA scores (0-10) were significantly consistent with the conventional angiographic staging. Four grades based on this novel MRA scores correlated well with Suzuki's stages, with high sensitivity and specificity. CONCLUSIONS: These novel MRA grades can be a reliable alternative to conventional staging. By employing these novel MRA grades, the use of conventional angiography can be avoided for the purpose of evaluation of the stages of moyamoya disease.

Adolescent↗
PubMed2005

[Clinicopathology, clonality, and hormone production profile of prolactinoma].

OBJECTIVE: To analyze the hormone production profiles of prolactinoma and to analyze the clonality of prolactinoma. METHODS: Clinicopathologic factors were studied in 123 patients with prolactinoma, 40 males and 83 females, aged 31.9 +/- 12.2 (16 approximately 65) who underwent resection of tumor in Japan. The specimens were fixed in either 10% neutral buffered formalin or 70% alcohol and used for light microscopy. DNA was extracted from 26 samples of alcohol-fixed tissue from female patients for human androgen receptor gene (HUMARA) assay. The data underwent Spearman rank correlation analysis and nonparametric Mann-Whitney U test. RESULTS: sixty-one cases (50%) were pure prolactinoma and 62 cases (50%) were plurihormonal prolactinoma. Spearman rank correlation analysis revealed that age was significantly positively correlated with serum prolactin (PRL) level (P = 0.0002), and tumor volume (P < 0.0001); and tumor volume was significantly positively correlated with serum PRL level (P < 0.0001). Multiple regression analysis showed a significant correlation only between tumor volume and serum PRL level (multiple correlation coefficient = 0.622, coefficient of multiple determination = 0.387, t = 7.59, P < 0.0001). Mann-Whitney U test revealed that the invasiveness of tumor was significantly positively correlated with the serum PRL level (P < 0.0001), volume of tumor (P < 0.0001), and the age of patient (P = 0.0003); that the sex of patient was significantly positively correlated with the pre-and post-operative serum PRL levels (both P < 0.0001) and the tumor volume (P < 0.0001); and that male patients had significantly higher PRL levels and larger adenomas(P < 0.0001, P < 0.0001 respectively). The HUMARA assay disclosed that 11 of the 13 plurihormonal prolactinomas (85%) were compatible with monoclonal origin. CONCLUSION: Prolactinoma secrets not only PRL but also other pituitary hormones. Most multihormone producing prolactinomas are monoclonal in origin.

Adolescent↗
PubMed2005

Abnormal primary somatosensory function in unilateral polymicrogyria: an MEG study.

The purpose of this study is to investigate the primary somatosensory function in patients with unilateral polymicrogyria. Somatosensory evoked fields (SEFs) due to median and posterior tibial nerve stimulation were compared in the normal and dysplastic cortices of five patients with unilateral polymicrogyria. SEFs were observed in all five normal hemispheres and three dysplastic hemispheres. Latencies of N20m and P38m, the first cortical components of and SEFs for median nerve and tibial nerve stimulation, were all within the normal range in both normal and dysplastic hemispheres. The amplitudes of the N20m and P38m in the dysplastic hemispheres were smaller in one patient and larger in two patients compared to the normal hemispheres. Equivalent current dipoles of N20m and P38m were localized on the anatomical central sulcus of the normal hemispheres and over the central area of the dysplastic hemispheres. P38m dipoles were localized medial and upward to the N20m dipole in both normal and dysplastic hemispheres. N20m dipole orientation was normal in all normal hemispheres and in one dysplastic hemisphere, but abnormally inferior in two dysplastic hemispheres. P38m dipole had normal medial orientation in all hemispheres except one dysplastic hemisphere. Abnormality of the primary somatosensory function in the dysplastic cortex of patients with unilateral polymicrogyria was clearly demonstrated by magnetoencephalography with high resolution in time and space. The normal somatotopic arrangement was preserved.

Adolescent↗
PubMed2005

Delayed lymphocytic infundibuloneurohypophysitis following successful transsphenoidal treatment of Cushing's disease.

Lymphocytic infundibuloneurohypophysitis is a rare disorder in which neurohypophyseal function is impaired by an autoimmune process. Although several etiologies for this rare entity have been suggested, its occurrence following transsphenoidal adenomectomy has not been reported. A 20-year-old man presented with diabetes insipidus - seven years after successful transsphenoidal microadenomectomy for Cushing's disease, first diagnosed at the age of 13. Seven years later, he developed fairly rapid onset of polydipsia and polyuria. Magnetic resonance imaging demonstrated swelling of the posterior pituitary gland with thickening of the pituitary stalk. Endocrinological evaluation revealed neurohypophyseal dysfunction without the adenohypophysis being affected. On the basis of these findings, a diagnosis of lymphocytic infundibuloneurohypophysitis was made. The mass lesion of the posterior pituitary resolved after the administration of corticosteroids for two months and no operation was required. Lymphocytic infundibuloneurohypophysitis should be considered in the differential diagnosis of pituitary mass lesions following transsphenoidal surgery, especially when the mass is confined to the posterior pituitary gland with neurohypophyseal function being compromised.

Adenoma↗
PubMed2005

Problems in blood alcohol testing of severely injured drivers brought to emergency departments in Japan.

Breath alcohol tests are widely used to control DUI (driving under the influence) in Japan. However, this test is not applied to injured drivers transported to emergency hospitals. In such cases, BAC (blood alcohol concentration) testing should be done to prove DUI. In this paper, we tried to clarify two important issues on the BAC testing in Japan using a questionnaire survey and experiments about contamination of antiseptic ethanol. First, we have described the doctor's dilemma with DUI cases; our present questionnaire survey showed that the police often request the doctor to volunteer blood samples of the suspected drunk drivers brought to emergency hospitals since they have not been granted the right to order blood sampling in Japan. Then, doctors face a serious dilemma whether comply with the police request or not, resulting in widely different responses. Secondly, we have estimated the effects of antiseptic ethanol routinely used as a dermal antiseptic on the BAC tests. Our present experiments showed that uptake of ethanol can occur under certain conditions. Given the actual conditions outlined in the questionnaire, there seem to be a definite risk of ethanol contamination in BAC testing. Obviously, the time has come to discuss problems in BAC testing of injured drivers brought to emergency hospitals in Japan.

Accidents, Traffic↗
PubMed2005

Diagnostic value of super-selective bilateral cavernous sinus sampling with hypothalamic stimulating hormone loading in patients with ACTH-producing pituitary adenoma.

AIMS: Early diagnosis and early treatment by transsphenoidal surgery is desirable for ACTH-producing pituitary microadenoma, but accurate localization of the functional lesion is not always possible before surgery because magnetic resonance (MR) imaging may provide false negative and/or positive findings. The diagnostic value of super-selective bilateral cavernous sinus sampling with the administration of corticotropin-releasing hormone (CRH) was assessed in patients with functioning ACTH-producing pituitary adenoma. METHODS: Fifteen patients with pituitary adenoma (14 with microadenoma) aged from 23 to 74 years (mean 46.7 years) underwent cavernous sinus sampling with or without the CRH loading test and subsequent transsphenoidal surgery in our institute from October 1997 through to November 2002. MR imaging including dynamic scan failed to detect the adenomatous lesion in all patients. To eliminate the bias due to uneven blood flow in the cavernous sinuses and the multi-hormonal response to CRH administration, the ACTH/FSH ratios were evaluated. The inter-cavernous gradient (ICG) was calculated as the higher/lower ACTH venous blood levels in the right and left cavernous sinuses with or without CRH loading. The adjusted ICG was calculated using the ACTH/FSH ratios. The results were compared with the surgical findings. An ICG of 1.4 or greater was considered to indicate the localization of the responsible lesion. RESULTS: Transsphenoidal surgery revealed the functioning lesion on the right in five cases, the left in six, the midline in three and the bilateral lateral wings (double adenoma) in one. Adjusted ICG with CRH loading had a localization accuracy of 93.3% (14/15), which was significantly higher than that of 73.3% (11/15) using ICG without hypothalamic stimulating hormone loading (p = 0.0402). CONCLUSIONS: Super-selective cavernous sinus sampling with hypothalamic stimulating hormone administration can provide accurate localization of the responsible lesion in patients with ACTH-producing pituitary adenoma.

Adenoma↗
PubMed2004

Vaccination with tumor cell lysate-pulsed dendritic cells augments the effect of IFN-beta gene therapy for malignant glioma in an experimental mouse intracranial glioma.

Interferon-beta (IFN-beta) has been used as an antitumor drug against human glioma, melanoma and medulloblastoma since the 1980s. Recently, we developed a new gene therapy using the IFN-beta gene against malignant gliomas and then began clinical trials in 2000. Since stimulation of immune system was one mechanism of antitumor effect induced by IFN-beta gene therapy, we hypothesized that combination of IFN-beta gene therapy with immunotherapy might increase its effectiveness. In the present study, we tested whether combination therapy with IFN-beta gene therapy and immunotherapy using tumor cell lysate-pulsed dendritic cells (DCs) would increase the efficacy of IFN-beta gene therapy. In an experimental mouse intracranial glioma (GL261), which cannot be cured by either IFN-beta gene therapy or DC immunotherapy alone, IFN-beta gene therapy following DC immunotherapy resulted in a significant prolongation in survival of the mice. Moreover, when this combination was performed twice, 50% of treated mice survived longer than 100 days. Considering these results, this combination therapy may be one promising candidate for glioma therapy in the near future.

Animals↗
PubMed2004

Mutations in 14 Y-STR loci among Japanese father-son haplotypes.

In the present study 161 Japanese father/son haplotype transfers in 147 pedigrees were analyzed at 14 Y-STRs with two multiplex PCR-based typing systems. Five isolated single repeat mutations were identified at the DYS389I, DYS439, Y-GATA-H4, DYS389II and DYS391 loci, and a pedigree showing triple alleles at the DYS385 locus (a duplicate locus) without allelic discrepancy between the father and son was also observed. The overall mutation rate estimated across the 14 Y-STRs in the Japanese population was 0.22%/locus/meiosis (95% C.I. 0.09-0.51%). This rate was not significantly different (p>0.05) from those of autosomal STRs and Y-STRs in other populations, including German, Austrian, Polish and Norwegian populations. Furthermore, 138 haplotypes were identified in 147 pedigrees with a haplotype diversity value of 0.9983. Therefore, a combination of the two systems should permit effective analysis with sufficient discriminatory power.

Alleles↗
PubMed2004

A novel susceptibility locus for moyamoya disease on chromosome 8q23.

Moyamoya disease (MIM 252350) is characterized by stenosis or occlusion of the terminal portions of the bilateral internal carotid arteries and by abnormal vascular networks at the base of the brain. There is a high incidence of moyamoya disease in Asia, especially in Japan. Multifactorial inheritance is estimated with lambda(s)>40. Previous linkage studies have indicated that susceptibility loci for the disease are located on chromosomes 3p, 6q, and 17q. In the present study, we searched for loci linked to the disease in 12 Japanese families using 428 microsatellite markers and found significant evidence for linkage to 8q23 [maximum LOD score (MLS) of 3.6] and suggestive evidence for linkage to 12p12 (MLS=2.3). The present study revealed a novel locus for moyamoya disease.

Chromosome Mapping↗
PubMed2004

PTEN gene mutation and high MIB-1 labeling index may contribute to dissemination in patients with glioblastoma.

Dissemination of glioblastomas is often observed, but the underlying mechanism is not well clarified especially from the genetic viewpoints. The present study examined whether PTEN gene mutations and MIB-1 labeling index (LI) correlate with the dissemination in 39 consecutive patients with glioblastomas. Dissemination was defined as leptomenigeal enhancement by magnetic resonance imaging performed in all patients every 2-3 months. We examined PTEN mutations in 26 patients using cDNA-based direct sequencing and MIB-1 LI in 38 patients. Median survival time of the 39 patients was 16.2 months. Dissemination was found in 17 of 39 patients (43.6%). PTEN mutation was significantly associated with dissemination (P=0.0140), and higher MIB-1 LI (> or =35%) resulted in earlier dissemination (P=0.0156). Kaplan-Meier survival plots showed a significantly poorer survival for patients with PTEN mutation (P=0.0012). The results indicate that the evaluation of PTEN mutation and MIB-1 LI are useful to predict dissemination and prognosis of glioblastomas.

Adult↗
PubMed2004

Preoperative visualization of microvascular compression of cranial nerve IX using constructive interference in steady state magnetic resonance imaging in glossopharyngeal neuralgia.

We report a case of successfully treated glossopharyngeal neuralgia, in whom preoperative magnetic resonance imaging (MRI) with a sequence of constructive interference in steady-state (CISS) precisely delineated microvascular compression to the glossopharyngeal nerve at its cisternal portion. A 70-year old female experienced paroxysmal and excruciating pain, starting in the right ear and descending to the tongue and throat. The pain was brief, burning and triggered by swallowing food and drinks. Preoperative CISS-MRI delineated a small vascular loop compressing the glossopharyngeal nerve at its cisternal portion. The patient was diagnosed with glossopharyngeal neuralgia, and then, microvascular decompression surgery was performed. Intraoperative inspection revealed that the glossopharyngeal nerve root was in contact with a small arterial loop at its cisternal portion and was deformed as demonstrated by preoperative CISS-MRI. The glossopharyngeal nerve was displaced using a piece of Teflon felt, freeing it from the arterial loop compression. The patient's neuralgia resolved immediately after surgery. During a period of 2-years follow up, no recurrence of the neuralgia has occurred. The usefulness of CISS-MRI for the diagnosis of glossopharyngeal neuralgia is discussed.

Aged↗
PubMed2004

Intractable vomiting as an early clinical symptom of cerebrospinal fluid seeding to the fourth ventricle in patients with high-grade astrocytoma.

OBJECT: Cerebrospinal fluid (CSF) seeing of high-grade astrocytoma is common, but the early clinical symptoms are not well characterized. Here, we report five patients with disseminated high-grade astrocytoma in the fourth ventricle region who presented with intractable vomiting prior to the detection of the metastatic deposits with enhancement. PATIENTS AND METHODS: From 1994 to 2000, 133 patients of high-grade astrocytoma were treated in our institute and were followed up until December 2002. Follow-up magnetic resonance (MR) imaging was performed in all patients every 2-3 months. The CSF seeding was defined as leptomeningeal enhancement. Signs and symptoms of CSF seeding were checked at the monthly outpatient examination. RESULTS: Among them, 5 patients aged from 27 to 58 years (mean 43.8 years) with one anaplastic astrocytoma and four glioblastomas showed intractable vomiting without signs of high intracranial pressure as evaluated by MR imaging or ocular fundus examination prior to the detection of the fourth ventricle dissemination. Fourth ventricle dissemination appeared 1-3 months after vomiting in five patients. One patient with glioblastoma received gamma knife radiotherapy for a fourth ventricle lesion appearing as a high intensity area on T2-weighted imaging before the appearance of the enhanced nodule, and this lesion was cured. Four patients died of progression of the fourth ventricle lesion. CONCLUSION: Intractable vomiting may be an early clinical symptom of CSF seeding to the fourth ventricle in patients with high-grade astrocytoma. Early detection and immediate radiotherapy for this lesion are recommended to control fourth ventricle dissemination.

Adult↗
PubMed2004

Two different mechanisms of apoptosis resistance observed in interferon-beta induced apoptosis of human glioma cells.

Interferon (IFN)-beta is known to exert cytostatic or cytocidal effects in human glioma cells and is widely used in the treatment for gliomas. However, precise mechanisms of cell death induced by IFN-beta are not well understood. In this study, the authors investigated the intracellular signal transduction of IFN-beta in human glioma cells. The cell death process observed in susceptible cells SK-MG-1 was accompanied by characteristic morphological changes of apoptosis, processing of caspases, and DNA fragmentation. Use of caspase inhibitors confirmed the activation of caspases, however activated executioner caspase was caspase-7 rather than caspases-3 or -6. Activation of DNA endonuclease, DNase-gamma was also observed. Observation of other IFN-beta relatively resistant glioma cells (U251SP, T98G, U251MG, U87MG, SK-AO2) revealed two different mechanisms of apoptosis resistance. In contrast to T98G, U87MG, and SK-AO2 which showed no activation of caspases, surprisingly, all the apoptosis process except DNase-gamma activation was observed in U251SP and U251MG cells. Collectively, these findings indicate that IFN-beta induced apoptosis in human glioma cells through activation of caspase-7 and activation of DNase-gamma. The similar activations of caspases were found also in some of the apoptosis resistant cells. These findings may help to improve the IFN-beta therapy in near future.

Antineoplastic Agents↗