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Biomedical subjects

Toyojiro Matsuishi

Publications and source records attributed to Toyojiro Matsuishi.

At least 19 recordsLinked to original sources
PubMed2006

Prefrontal cerebral blood volume patterns while playing video games--a near-infrared spectroscopy study.

Video game playing is an attractive form of entertainment among school-age children. Although this activity reportedly has many adverse effects on child development, these effects remain controversial. To investigate the effect of video game playing on regional cerebral blood volume, we measured cerebral hemoglobin concentrations using near-infrared spectroscopy in 12 normal volunteers consisting of six children and six adults. A Hitachi Optical Topography system was used to measure hemoglobin changes. For all subjects, the video game Donkey Kong was played on a Game Boy device. After spectroscopic probes were positioned on the scalp near the target brain regions, the participants were asked to play the game for nine periods of 15s each, with 15-s rest intervals between these task periods. Significant increases in bilateral prefrontal total-hemoglobin concentrations were observed in four of the adults during video game playing. On the other hand, significant decreases in bilateral prefrontal total-hemoglobin concentrations were seen in two of the children. A significant positive correlation between mean oxy-hemoglobin changes in the prefrontal region and those in the bilateral motor cortex area was seen in adults. Playing video games gave rise to dynamic changes in cerebral blood volume in both age groups, while the difference in the prefrontal oxygenation patterns suggested an age-dependent utilization of different neural circuits during video game tasks.

Adult↗
PubMed2006

Prediction of resistance to intravenous immunoglobulin treatment in patients with Kawasaki disease.

OBJECTIVES: The objective of this study was to find the predictors and generate a prediction score of resistance to intravenous immunoglobulin (IVIG) in patients with Kawasaki disease (KD). STUDY DESIGN: Patients diagnosed as having KD were sampled when they received initial high-dose IVIG treatment (2 g/kg dose) within 9 days of illness (n = 320). These patients were divided into 2 groups: the resistance (n = 41) and the responder (n = 279). The following data were obtained and compared between resistance and responder: age, sex, illness days at initial treatment, and laboratory data. RESULTS: Multivariate logistic regression analysis identified age, illness days, platelet count, alanine aminotransferase (ALT), and C-reactive protein (CRP) as significant predictors for resistance to IVIG. We generated prediction score assigning 1 point for (1) infants less than 6 months old, (2) before 4 days of illness, (3) platelet count or= 8 mg/dL, as well as 2 points for (5) ALT >or= 80 IU/L. Using a cut-off point of 3 and more with this prediction score, we could identify the IVIG-resistant group with 78% sensitivity and 76% specificity. CONCLUSIONS: Resistance to IVIG treatment can be predicted using age, illness days, platelet count, ALT, and CRP. Randomized, multicenter clinical trials are necessary to create a new strategy to treat these high-risk patients.

Acute Disease↗
PubMed2006

Risk factors associated with the need for additional intravenous gamma-globulin therapy for Kawasaki disease.

AIM: To investigate the characteristics of patients with Kawasaki disease who needed intravenous gamma-globulin (IVGG) re-treatment. METHODS: Using the database of the 17th nationwide survey in Japan, a total 11,366 patients were identified and analysed (1,855 re-treatment patients and 9,511 responders). RESULTS: Multivariate logistic regression analysis showed that male sex (odds ratio (OR) 1.26; 95% CI 1.14-1.40), complete cases (OR 1.39; 95% CI 1.07-1.80), recurrence (OR 1.47; 95% CI 1.15-1.88), IVGG treatment within 4 d of illness (OR 2.05; 95% CI 1.84-2.27), daily dose of initial IVGG less than 1,000 mg/Kg (OR 0.54; 95% CI 0.48-0.61), exanthema (OR 2.03; 95% CI 1.62-2.56), lips and oral lesions (OR 1.57; 95% CI 1.24-1.98), peripheral extremities changes (OR 1.85; 95% CI 1.54-2.22), and cervical lymphadenopathy (OR 1.89; 95% CI 1.66-2.16) were independent risk factors associated with the need for IVGG re-treatment. CONCLUSION: Male sex, recurrence, and treatment with IVGG at a dose of 1,000 mg/d or less within 4 d of illness onset are independent risk factors associated with the need for IVGG re-treatment.

Exanthema↗
PubMed2006

Ischemia-induced angiogenesis: role of inflammatory response mediated by P-selectin.

P-selectin is a 140-kDa glycoprotein expressed on endothelial cells and platelets. P-selectin mediates the tethering and rolling of leukocytes along the endothelium, an early step of leukocyte extravasation. Although inflammation is a requisite process for ischemia-induced angiogenesis, little is known regarding the role of P-selectin in angiogenesis in the setting of tissue ischemia. We examined whether ischemia-induced angiogenesis is altered in P-selectin knockout (P-selectin(-/-)) mice. Angiogenesis was evaluated in a surgically induced hind-limb ischemia model using laser Doppler blood flowmetry (LDBF) and histological capillary density (CD). After left hind-limb ischemia, the ischemic/normal limb LDBF ratio was persistently lower in P-selectin(-/-) mice compared with wild-type (WT) mice. CD was also significantly lower in P-selectin(-/-) mice than in WT mice on Postoperative Day 14. Fewer numbers of total CD45+ inflammatory leukocytes infiltrated into the ischemic tissues in P-selectin(-/-) mice than in WT mice, and immunohistochemical analysis revealed the number of infiltrated leukocytes expressing vascular endothelial growth factor was also decreased in P-selectin(-/-) mice. P-selectin mRNA expression was augmented after hind-limb ischemia in WT mice. In conclusion, P-selectin may play an important role in ischemia-induced angiogenesis by promoting early inflammatory mononuclear cell infiltration. P-selectin would become one possible target molecule for modulating inflammatory angiogenesis.

Animals↗
PubMed2006

Cell cycle-specific changes in hTERT promoter activity in normal and cancerous cells in adenoviral gene therapy: a promising implication of telomerase-dependent targeted cancer gene therapy.

Based on the finding that telomerase is reactivated solely in cancer cells, the human telomerase reverse transcriptase (hTERT) promoter has recently been used to target cancer cells by gene therapy. The recent, surprising observation that telomerase is physiologically activated even in normal somatic cells during S-phase has raised concerns as to the safety of this methodology. To clarify this issue, the present study carefully examined the changes in endogenous telomerase activities, hTERT mRNA expression, and hTERT promoter-based transgene expression in normal and cancer cells at synchronized phases of the cell cycle. Telomerase activity and hTERT expression were detected at variable, but relatively high, levels in all 12 cancer cell lines, while both were undetectable in the 11 normal cell lines. In HepG2 cancer cells, the highest levels of hTERT expression and telomerase activity, seen in the G(1)/S- and S-phases, were 2-3-fold higher than the lowest levels of both, observed in G(0)-phase and during asynchronization. No hTERT expression or telomerase activitiy could be detected in normal WI-38 fibroblasts at any phase of the cell cycle, including S-phase. Consequently, activity of the shorter hTERT promoter, which was transferred into HepG2 cancer cells via adenovirus transduction, was stronger than that of the longer hTERT promoter at all phases and that of two representatives of ubiquitously strong promoters, at both S-phase and asynchronization, but not at G(0)-phase. In contrast, neither of hTERT promoters induced detectable transgene expressions in normal WI-38 cells at any cell cycle phase, including S-phase. These results, particularly the lack of problematic levels of S-phase-specific activation of hTERT promoters in normal cells, have promising implications for hTERT promoter-based targeted gene therapy of cancer.

Adenoviridae↗
PubMed2005

Mitochondrial tRNA gene mutations in patients having mitochondrial disease with lactic acidosis.

Lactic acidosis has been associated with a variety of clinical conditions and can be due to mutation in nuclear or mitochondrial genes. We performed mutations screening of all mitochondrial tRNA genes in 44 patients who referred as hyperlactic acidosis. Patients showed heterogeneous phenotypes including Leigh disease in four, MELAS in six, unclassified mitochondrial myopathy in 10, cardiomyopathy in five, MERRF in one, pure lactic acidosis in six, and others in 12 including facio-scaplo-femoral muscular dystrophy (FSFD), familial cerebellar ataxia, recurrent Reye syndrome, cerebral palsy with mental retardation. We measured enzymatic activities of pyruvate dehydrogenase complex, and respiratory chain enzymes. All mitochondrial tRNA genes and known mutation of ATPase 6 were studied by single strand conformation polymorphism (SSCP), automated DNA sequence and PCR-RFLP methods. We have found one patient with PDHC deficiency and six patients with Complex I+IV deficiency, though the most of the patients showed subnormal to deficient state of respiratory chain enzyme activities. We have identified one of the nucleotide changes in 29 patients. Single nucleotide changes in mitochondrial tRNA genes are found in 27 patients and one in ATPase 6 gene in two patients. One of four pathogenic point mutations (A3243G, C3303T, A8348G, and T8993G) was identified in 12 patients who showed the phenotype of Leigh syndrome, MELAS, cardimyopathy and cerebral palsy with epilepsy. Seventeen patients have one of the normal polymorphisms in the mitochondrial tRNA gene reported before. SSCP and PCR-RFLP could detect the heteroplasmic condition when the percentage of mutant up to 5, however, it cannot be observed by direct sequencing method. It is important to screen the mtDNA mutation not only by direct sequence but also by PCR-RFLP and the other sensitive methods to detect the heroplasmy when lactic acidosis has been documented in the patients who are not fulfilled the criteria of mitochondrial disorders.

Acidosis, Lactic↗
PubMed2005

Survivin-responsive conditionally replicating adenovirus exhibits cancer-specific and efficient viral replication.

Although a conditionally replicating adenovirus (CRA) exhibiting cancer-selective replication and induction of cell death is an innovative potential anticancer agent, current imperfections in cancer specificity and efficient viral replication limit the usefulness of this technique. Here, we constructed survivin-responsive CRAs (Surv.CRAs), in which expression of the wild-type or mutant adenoviral early region 1A (E1A) gene is regulated by the promoter of survivin, a new member of the inhibitor of apoptosis gene family. We explored the cancer specificity and effectiveness of viral replication of Surv.CRAs, evaluating their potential as a treatment for cancer. The survivin promoter was strongly activated in all cancers examined at levels similar to or even higher than those seen for representative strong promoters; in contrast, low activity was observed in normal cells. Surv.CRAs efficiently replicated and potently induced cell death in most types of cancer. In contrast, minimal viral replication in normal cells did not induce any detectable cytotoxicity. A single injection of Surv.CRAs into a preestablished tumor expressing survivin, even at relatively low levels, induced significant tumor death and inhibition of tumor growth. Furthermore, Surv.CRAs were superior to telomerase-dependent CRAs, one of the most effective CRAs that have been examined to date, both in terms of cancer specificity and efficiency. Thus, Surv.CRAs are an attractive potential anticancer agent that could effectively and specifically treat a variety of cancers.

Adenoviridae↗
PubMed2005

L-arginine improves the symptoms of strokelike episodes in MELAS.

Based on the hypothesis that mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS) are caused by impaired vasodilation in an intracerebral artery, the authors evaluated the effects of administering l-arginine, a nitric oxide precursor. Patients were administered L-arginine intravenously at the acute phase or orally at the interictal phase. L-arginine infusions significantly improved all strokelike symptoms, suggesting that oral administration within 30 minutes of a stroke significantly decreased frequency and severity of strokelike episodes.

Administration, Oral↗
PubMed2005

Methyl-CpG binding protein 2 gene (MECP2) variations in Japanese patients with Rett syndrome: pathological mutations and polymorphisms.

A total of 45 different mutations of methyl-CpG-binding protein 2 gene (MECP2) were identified in 145 of 219 Japanese patients with typical or atypical Rett syndrome (RTT) (66.2%). A missense mutation, T158M was the most common mutation of MECP2, identified in 22 (19.1%) patients, followed by four nonsense mutations, R168X (14.8%), R270X (13.0%), R255X (9.6%), and R294X (6.1%) in 115 patients with classical RTT. Two missense mutations, R133C (33.3%) and R306C (23.3%), and a nonsense mutation, R294X (13.3%), were common in 30 patients with atypical RTT, including the preserved speech variant (PSV). Frameshift mutations due to nucleotide deletion or insertion were identified in 22 patients with MECP2 mutations, and one of them had a 3.6 kb deletion encompassing exons 3 and 4. Three patients with classical RTT had a splicing anomaly. The wide spectrum of phenotypic variability in patients with RTT has been considered to be correlated with the mutation type and location in MECP2, and X-inactivation. However, most patients showed a random X-inactivation pattern evaluated by an androgen receptor gene polymorphism in this study, suggesting that a skewed X-inactivation might not be a main modification factor on clinical phenotypes of RTT. In addition, three new missense mutations, P176R, A378V and T479M, were identified in patients with RTT, but also in healthy Japanese, indicating that these mutations are non-pathogenic in Japanese. Information about rare polymorphic variations is very important for the molecular diagnosis of RTT, although rare polymorphic variants might differ among ethnic groups.

Adolescent↗
PubMed2005

Transient Haemophilus influenzae type b bacteremia in a healthy child.

Occult bacteremia with Streptococcus pneumoniae (S. pneumoniae) is sometimes experienced in general clinics, while that with Haemophilus influenzae type b (Hib) is less common and mostly develops to serious central nervous infection. Recently we encountered a patient with bacteremia due to Hib, in whom bacteremia recovered spontaneously without intravenous antibiotic therapy. A previously healthy 17-month-old girl was brought to our hospital with the complaint of high fever. Although her clinical condition did not present any of meningeal signs, the laboratory data on the first day showed prominent leukocytosis and sepsis work-up was done. Two days later (third day of illness), blood culture grew Haemophilus influenzae sensitive to ampicillin and the strain isolated from blood was identified as Hib. The febrile condition soon disappeared and bacteremia resolved with the negative result of the next blood culture. It is not clear about the precise mechanisms of this phenomenon, however, it is an extremely rare case for Hib bacteremia to resolve spontaneously.

Bacteremia↗
PubMed2005

[Effects of milnacipran on neuronal excitability and synaptic transmission in neurons of the rat locus coeruleus].

Effects of milnacipran (MIL), a selective serotonin and noradrenaline (NA) reuptake inhibitor, on the neuronal excitability and synaptic transmission in the rat locus coeruleus (LC) were examined by intracellular and whole-cell patch-clamp recording techniques. We compared MIL and methylphenidate (MPH), a selective NA and dopamine reuptake inhibitor, as a therapeutic agent for attention deficit/hyperactivity disorder. Application of MPH (1-100 microM) and MIL (1-100 microM) to artificial cerebrospinal fluid (ACSF) produced a hyperpolarizing response in LC neurons in a concentration-dependent manner. Spontaneous firing of LC neurons was blocked during the hyperpolarization. The MIL-induced hyperpolarization was blocked by yohimbine (1 microM), an antagonist for alpha-adrenoceptors. These results suggest that the MIL-induced hyperpolarization is mediated by NA via alpha2-adrenoceptors in LC neurons. Under the whole-cell patch-clamp condition, prolonged application of MIL produced an outward current which lasted as long as MIL existed in the ACSF. The outward current induced by NA was enhanced by MIL in LC neurons. MIL enhanced the amplitude and duration of the inhibitory postsynaptic potential, while it depressed the excitatory postsynaptic potential. The results indicated that both MIL and MPH showed almost the same effects on neuronal activity and synaptic transmission in the rat LC. These results suggest that MIL increases the concentration of NA at synaptic clefts by inhibiting the NA reuptake system in the rat LC.

Animals↗
PubMed2005

[Sudden death in Rett syndrome].

Rett syndrome is a unique disorder mainly in girls characterized by global deceleration of psychomotor development and subsequent loss of acquired cognitive and motor skills, occurring after 6 to 18 months of apparently normal development. Previous study described that 26% of the cause of their death was sudden and unexpected. Although the cause of sudden death is still unknown, respiratory disorder, cardiac arrhythmia, and severe seizure might be related to sudden death. The possibility of sudden death should be informed to families of patients with Rett syndrome. Electrocardiogram should be examined in older patients, because prolongation of QTc and T wave abnormalities increase with advancing stage.

Death, Sudden↗
PubMed2004

Early intravenous gamma-globulin treatment for Kawasaki disease: the nationwide surveys in Japan.

OBJECTIVE: To determine the optimal period of intravenous gamma-globulin (IVGG) treatment, using the database from nationwide Kawasaki disease surveys in Japan. STUDY DESIGN: We selected patients who first visited a doctor within 3 days of illness and received IVGG treatment within 9 days of illness. We divided these patients into 2 groups: an early group (treated on days 1-4: 4731 cases) and a conventional group (days 5-9: 4020 cases). We compared the rate of additional IVGG and prevalence of cardiac sequelae between these groups. RESULTS: The rate of additional IVGG in the early group was significantly higher than those of the conventional group (OR, 1.12 [95% CI, 1.10-1.16]). There were no significant differences in cardiac sequelae between the two groups. CONCLUSIONS: There is no evidence that IVGG treatment on day 4 or earlier has greater efficacy in preventing cardiac sequelae than treatment on days 5 to 9. In addition, early treatment is likely to result in a greater requirement for additional IVGG. However, there is also no evidence that early treatment increases the prevalence of cardiac sequelae in a clinical practice setting, where additional IVGG can be given to those whose initial treatment fails.

Child, Preschool↗
PubMed2004

Noonan syndrome, moyamoya-like vascular changes, and antiphospholipid syndrome.

This reports describes a 12-year-old Japanese female with Noonan syndrome who had antiphospholipid syndrome and moyamoya-like vascular changes. She presented choreic movements in her face and extremities. She manifested phenotypic features of Noonan syndrome with short stature, mental retardation, and a webbed neck. Magnetic resonance angiography revealed occlusion of bilateral internal carotid arteries and moyamoya-like vascular changes around the basal ganglion region. Pimozide completely resolved the patient's choreic movements. Tests for anticardiolipin antibody and lupus anticoagulant were positive. The patient has manifested no symptoms for 2 years with pimozide, aspirin, and growth hormone treatment, without further aggravation of moyamoya-like vascular changes. This article is the first report of Noonan syndrome with antiphospholipid syndrome and moyamoya-like vascular lesions.

Antiphospholipid Syndrome↗
PubMed2004

Pyruvate dehydrogenase E1alpha subunit deficiency in a female patient: evidence of antenatal origin of brain damage and possible etiology of infantile spasms.

Enlargement of the lateral ventricles and atrophy of the brain were documented ultrasonographically in utero at as early as 28th week of gestation in a female patient with lactic acidosis due to deficiency of the pyruvate dehydrogenase E1alpha subunit, demonstrating that the changes characteristic of this disease can occur antenatally. The mechanism of infantile spasms in this disease may be linked to mosaicism of the brain cells involving the normal enzyme and the mutant enzyme.

Electroencephalography↗
PubMed2004

Older age is a risk factor for the development of cardiovascular sequelae in Kawasaki disease.

OBJECTIVES: To clarify the characteristics of Kawasaki disease (KD) in children 6 years and older and to determine whether age is a risk factor for cardiovascular abnormalities. METHODS: Patients who had KD and were reported between 1999 and 2000 in the 16th nationwide survey of KD in Japan (n = 15,314) were analyzed. Patients who were aged 6 years or older (older group) were matched with patients who were aged 6 months to 3 years and were treated at the same hospital (younger groups). The total number of analyzed patients was 1498 (749 matched pairs). RESULTS: The proportion of complete KD in the older group was similar to that in the younger group. Recurrent cases in the older group were significantly more common than those in the younger group (9% vs 2%). The proportion of patients who were treated with intravenous gamma-globulin in the older group was significantly lower than that in the younger group (82% vs 87%). The proportion of older group patients who were treated with intravenous gamma-globulin at or after 7 days of illness was significantly higher than that in the younger group (35% vs 14%). There was a higher prevalence of cardiovascular abnormalities in the older group than in the younger group (20% vs 15%). Multivariate logistic regression analysis showed that older age was an independent risk factor for cardiovascular sequelae (odds ratio: 1.58; 95% confidence interval: 1.01-2.46). CONCLUSIONS: In children older than 6 years, age is an independent risk factor for cardiovascular sequelae in KD.

Age Factors↗