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Biomedical subjects

Masayoshi Kawai

Publications and source records attributed to Masayoshi Kawai.

18 recordsLinked to original sources

Decreased serum levels of hepatocyte growth factor in male adults with high-functioning autism.

BACKGROUND: The mechanisms underlying the pathophysiology of autism are currently unknown. Given the role of hepatocyte growth factor (HGF) in brain development, we hypothesized that HGF plays a role in the pathophysiology of autism. In this study, we studied whether serum HGF levels are altered in subjects with high-functioning autism. METHODS: Using an enzyme-linked immunosorbent assay (ELISA), we measured serum levels of HGF in 17 male adults with high-functioning autism and age-matched 18 male healthy subjects. RESULTS: The serum levels (503.5+/-160.5 pg/mL (mean+/-SD)) of HGF in the subjects with high-functioning autism were significantly (Mann-Whitney U=34.0, p<0.001) lower than those (817.6+/-232.4 pg/mL (mean+/-SD)) of control subjects. However, there were no correlations between serum HGF levels and clinical variables in the patients. CONCLUSIONS: This study suggests that reduced HGF levels may play a role in the pathophysiology of high-functioning autism.

Adult↗

Decreased serum levels of epidermal growth factor in adult subjects with high-functioning autism.

BACKGROUND: The neurobiological basis for autism remains poorly understood. Given the role of growth factors in brain development, we hypothesized that epidermal growth factor (EGF) may play a role in the pathophysiology of autism. In this study, we examined whether serum levels of EGF are altered in adult subjects with high-functioning autism. METHODS: We measured serum levels of EGF in the 17 male subjects with high-functioning autism and 18 age-matched healthy male subjects. RESULTS: The serum levels of EGF in the subjects with high-functioning autism (72.4 +/- 102.8 pg/mL [mean +/- SD]) were significantly lower (Mann-Whitney U = 22.0, p < .001) than those of normal control subjects (322.3 +/- 122.0 pg/mL [mean +/- SD]). However, there were no correlations between serum EGF levels and clinical variables in the subjects with autism. CONCLUSIONS: This study suggests that decreased levels of EGF might be implicated in the pathophysiology of high-functioning autism.

Adult↗

Increased levels of serum soluble L-selectin in unmedicated patients with schizophrenia.

OBJECTIVE: Numerous studies have linked schizophrenia with altered immune function. The selectin family of adhesion molecules plays a prominent role in immune/inflammatory responses. To further study the immunological processes in the pathophysiology of schizophrenia, we determined the serum levels of selectins in patients with schizophrenia. For specificity, we also investigated selectin levels in patients with major depression. METHOD: We studied 23 unmedicated patients with schizophrenia, 17 unmedicated patients with major depression, and 36 healthy subjects. The serum levels of three types of soluble-form selectin (sE-, sL- and sP-selectin) were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum sL-selectin levels were significantly higher in patients with schizophrenia than in either control subjects (p=0.005) or patients with major depression (p=0.02). No significant difference was found with regard to the level of either serum sE-selectin or sP-selectin. CONCLUSION: Elevated sL-selectin levels in patients with schizophrenia may represent immune system dysfunction and may be involved in the pathogenesis of the illness.

Adult↗

Decreased serum levels of transforming growth factor-beta1 in patients with autism.

BACKGROUND: The neurobiological basis for autism remains poorly understood. Given the key role of transforming growth factor-beta1 (TGF-beta1) in brain development, we hypothesized that TGF-beta1 plays a role in the pathophysiology of autism. In this study, we studied whether serum levels of TGF-beta1 are altered in patients with autism. METHODS: We measured serum levels of TGF-beta1 in 19 male adult patients with autism and 21 age-matched male healthy subjects using enzyme-linked immunosorbent assay (ELISA). RESULTS: The serum levels (7.34+/-5.21 ng/mL (mean+/-S.D.)) of TGF-beta1 in the patients with autism were significantly (z=-5.106, p<0.001) lower than those (14.48+/-1.64 ng/mL (mean+/-S.D.)) of normal controls. However, there were no marked or significant correlations between serum TGF-beta1 levels and other clinical variables, including Autism Diagnostic Interview-Revised (ADI-R) scores, Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), aggression, Theory of Mind, and Intellectual Quotient (IQ) in patients. CONCLUSIONS: These findings suggest that decreased levels of TGF-beta1 may be implicated in the pathophysiology of autism.

Adolescent↗

Increased serum levels of glutamate in adult patients with autism.

BACKGROUND: Precise mechanisms underlying the pathophysiology of autism are currently unknown. Given the major role of glutamate in brain development, we have hypothesized that glutamatergic neurotransmission plays a role in the pathophysiology of autism. In this study, we studied whether amino acids (glutamate, glutamine, glycine, D-serine, and L-serine) related to glutamatergic neurotransmission are altered in serum of adult patients with autism. METHODS: We measured serum levels of amino acids in 18 male adult patients with autism and age-matched 19 male healthy subjects using high-performance liquid chromatography. RESULTS: Serum levels (mean = 89.2 microM, S.D. = 21.5) of glutamate in the patients with autism were significantly (t = -4.48, df = 35, p < 0.001) higher than those (mean = 61.1 microM, S.D. = 16.5) of normal controls. In contrast, serum levels of other amino acids (glutamine, glycine, d-serine, l-serine) in the patients with autism did not differ from those of normal controls. There was a positive correlation (r = 0.523, p = 0.026) between serum glutamate levels and Autism Diagnostic Interview-Revised (ADI-R) social scores in patients. CONCLUSIONS: The present study suggests that an abnormality in glutamatergic neurotransmission may play a role in the pathophysiology of autism.

Adolescent↗

Association analysis of SOD2 variants with methamphetamine psychosis in Japanese and Taiwanese populations.

SOD2 (superoxide dismutase 2) plays a crucial role in protecting the cells against damage caused by free radicals, by catalyzing their detoxification. On the other hand, cell damage caused by free radical generation following methamphetamine administration has been postulated as one of the possible pathophysiological mechanisms for methamphetamine psychosis. Hence, we investigated the association of SOD2 polymorphisms with the development of methamphetamine psychosis, in two independent populations of Japan and Taiwan. We recruited 116 patients with methamphetamine psychosis and 189 controls in Japan, and 135 patients with methamphetamine psychosis and 204 controls in Taiwan. The methamphetamine group was divided into two clinical subtypes: a transient type of psychosis (i.e., good prognosis) and a prolonged type of psychosis (i.e., poor prognosis), according to the course of the manifestation of psychosis. With reference to the genotypic and allelic frequencies of Ala/Val functional polymorphism in exon 2, we found significant differences between individuals with prolonged methamphetamine psychosis and control samples from Japan and Taiwan in the genotypic (P value 0.014 and 0.016, respectively) and in the allelic (P value 0.004 and 0.047, respectively) frequencies. Our results suggest that Ala/Val polymorphism of the SOD2 gene could be associated with the risk of developing methamphetamine psychosis.

Adolescent↗

A transient lesion in splenium of the corpus callosum in a patient with childhood-onset anorexia nervosa.

OBJECTIVE: Although a transient lesion in the splenium of the corpus callosum (SCC) has been reported predominantly regarding patients with epilepsia, it is of rare occurrence, and its underlying biological basis remains unknown. This is a report of an SCC lesion in a patient with anorexia nervosa (AN). METHOD: The patient was a 15-year-old girl with childhood-onset (11 years) and a protracted course of AN. On admission, the patient showed no apparent neurological abnormalities. Magnetic resonance imaging (MRI) scans revealed a circumscribed lesion in the SCC. We treated her with nutritional rehabilitation supplemented with B vitamins. RESULTS: One month later, the lesion completely disappeared, but her weight was not restored. CONCLUSION: Treatment with B-vitamin supplementation may be beneficial for the treatment of patients with AN, in cases in which the disorder develops at an early age before brain maturation (i.e., childhood-onset cases), along with an enduring course of malnutrition.

Adolescent↗

An association study between catechol-O-methyl transferase gene polymorphism and methamphetamine psychotic disorder.

OBJECTIVE: A series of methamphetamine psychosis reveals two kinds of clinical courses of methamphetamine psychosis: transient type and prolonged type. Furthermore, paranoid psychosis sometimes recurs without methamphetamine reuse, referred to as spontaneous relapse. Dysfunction of central dopaminergic neurotransmission has been implicated in the pathogenesis of these psychiatric states. Catechol-O-methyl transferase appears to play a unique role in regulating synaptic dopaminergic activity. This study aimed to investigate whether a functional polymorphism of the catechol-O-methyl transferase gene would be involved in the development of these psychiatric states. BASIC METHODS: We examined the functional polymorphism of val 158 met (catechol-O-methyl transferase) in 143 patients with methamphetamine psychosis and 200 healthy controls in Japan. The patients were divided into subgroups by several characteristic clinical features. MAIN RESULTS: We found a significant difference in the catechol-O-methyl transferase allele frequency between patients with spontaneous relapse and the controls (P=0.018, odds ratio=1.67). Odds ratio implied that the patients with spontaneous relapse had a nearly 1.7-fold higher rate of the low activity alleles (met) than the controls. CONCLUSIONS: Our results indicate that the met allele frequency of the catechol-O-methyl transferase is associated with patients who experienced methamphetamine psychosis and spontaneous relapse, suggesting that patients with a met allele appear to be at increased risk of an adverse response to methamphetamine.

Adult↗

Advanced paternal age associated with an elevated risk for schizophrenia in offspring in a Japanese population.

OBJECTIVE: Advanced paternal age at birth as a risk for schizophrenia in the adult offspring has been reported in previous studies exclusively conducted in Western countries and Israel. The question has arisen whether this finding could be replicated in countries with socially and culturally different attitudes toward marriage, including factors such as age at marriage. To address this question, we conducted a case-control study of a Japanese population. METHODS: The subjects were representative inpatients with a DSM-IV diagnosis of schizophrenia. Unrelated healthy volunteers were recruited as control subjects. This study was conducted as one of a series of the projects by use of "The Mother and Child Health Handbooks (MCHHs)," from which information on parental characteristics around the time of birth, including parental ages at birth, had been extracted and recorded on computer. RESULTS: Ninety-nine subjects with schizophrenia and 381 healthy control subjects enrolled for the study. Advanced paternal, but not maternal, age was associated with an elevated risk for schizophrenia. Reproducibility of the association across different cultures is suggestive of a causal link.

Adult↗

Characteristics of high-energy neutrons estimated using the radioactive spallation products of Au at the 500-MeV neutron irradiation facility of KENS.

We carried out a shielding experiment of high-energy neutrons, generated from a tungsten target bombarded with primary 500-MeV protons at KENS, which penetrated through a concrete shield in the zero-degree direction. We propose a new method to evaluate the spectra of high-energy neutrons ranging from 8 to 500 MeV. Au foils were set in a concrete shield, and the reaction rates for 13 radionuclides produced by the spallation reactions on the Au targets were measured by radiochemical techniques. The experimental results were compared with those obtained by the MARS14 Monte-Carlo code. A good agreement (between them) was found for energies beyond 100 MeV. The profile of the neutron spectrum, ranging from 8 to 500 MeV, does not depend on the thickness of the concrete shield.

Algorithms↗

Measurement and analysis of induced activities in concrete irradiated using high-energy neutrons at KENS Neutron Spallation Source Facility.

Precise estimation of induced activities in concrete shields for high-energy accelerator facilities is one of the most important issues that need to be solved, not only for the reduction of exposure for workers, but also for the reduction of radioactive wastes. Irradiation experiments have been performed by using the 500 MeV Neutron Spallation Source Facility in KEK. The large concrete assembly was placed in the direction of 0 degrees to the beamline. Two kinds of samples were placed at several positions in the assembly. The irradiation period was about 1 week and induced activities in the samples were measured until approximately 1.5 y after irradiation. From the comparison between the experiment and the available Monte Carlo calculation code system, good agreement was obtained for 24Na, 47Sc, 47Ca and 54Mn within a factor 2; however, large discrepancies were observed for some other nuclides.

Computer Simulation↗

Augmentation of milnacipran by risperidone in treatment for major depression.

Milnacipran, one of the serotonin noradrenaline reuptake inhibitors (SNRIs) to which venlafaxine and duloxetine belong, is a new antidepressant that has recently become available in many countries. Despite the advances in pharmacotherapy, almost one third of patients with depressive illness respond inadequately to monotherapy with such an antidepressant. We herein describe five patients with major depression who responded partially, but not fully, to milnacipran alone and remarkably improved with an adjunct of risperidone. In addition, milnacipran plus risperidone was found to be a useful augmentation for treatment-refractory depression in 3 of the 5 patients. The minimum dose of risperidone, 0.5 or 1 mg/d, was efficacious. The time of response after addition of risperidone was within 4 d. Our experience suggests that an augmentation therapy of milnacipran plus risperidone is useful for treating patients with depression who only partially respond to various types of antidepressants and for treatment-refractory depression.

Adult↗

The effects of dentate granule cell destruction on behavioral activity and Fos protein expression induced by systemic MDMA in rats.

In this study, we examined the effect of the s.c. administration of (+/-) 3,4-methylenedioxymethamphetamine (MDMA) or saline on locomotor activity and Fos expression following the bilateral destruction of hippocampal dentate granule cells by colchicine in rats. The lesioned animals, when administered s.c. saline, showed a significantly greater increase in locomotor activity compared to the intact animals, and revealed a marginally significant level of increased locomotor activity compared to the sham-lesioned animals. In addition, when the lesioned animals were given s.c. saline or MDMA, there was a significant increase in Fos expression in the nucleus accumbens core, but not in the medial prefrontal cortex, dorsolateral prefrontal cortex, anterior cingulate cortex, piriform cortex, dorsal striatum, or nucleus accumbens shell, compared to the intact and sham-lesioned animals. Overall, these results suggest that the nucleus accumbens core may be involved in the enhancement of locomotor activity induced by the injection of saline alone (stress loading) or MDMA following bilateral destruction of hippocampal dentate granule cells by colchicine.

Animals↗

Tacrolimus, a specific inhibitor of calcineurin, modifies the locomotor activity of quinpirole, but not that of SKF82958, in male rats.

In the present study, we examined the effect of tacrolimus, a specific inhibitor of calcineurin, on the locomotor activity elicited by the selective dopamine D(1) receptor agonist (+/-) 6-chloro-7,8-dyhydroxy-3allyl-1-phenyl-2,3,4,5-tetra-hydro-1H-benzazepine (SKF82958) and the dopamine D(2)/D(3) receptor agonist quinpirole, in male Wistar rats. Tacrolimus (0.5, 1, 2 or 5 mg/kg, i.p.) alone had no significant effect on basal locomotor activity. The dose-related increase in locomotor activity produced by the administration of SKF82958 (0.1, 1 or 5 mg/kg, i.p.) was not significantly altered by 2 mg/kg of tacrolimus. In addition, the increase in locomotor activity produced by 1 mg/kg of SKF82958 was not significantly altered by tacrolimus (0.5, 1, 2 or 5 mg/kg, i.p.). The administration of quinpirole (0.1, 0.25, 0.5, 1 or 3 mg/kg, i.p.) produced a biphasic response, with the minimum and maximal increase in locomotor activity occurring at 0.1 and 1 mg/kg, respectively. The pretreatment of 2 mg/kg of tacrolimus, compared to vehicle-treated animals, significantly lowered the dose of quinpirole that produce a maximal effect on locomotor activity from 1 to 0.5 mg/kg but did not significantly alter the minimum response. The increase in locomotor activity produced by 0.5 mg/kg of quinpirole was significantly potentiated by 0.5, 1, 2 or 5 mg/kg of tacrolimus compared to vehicle-treated animals. Our results suggest that calcineurin may play a role in the alteration of locomotor activity produced by dopamine D(2)/D(3) receptors, but not dopamine D(1) receptors.

Animals↗

Metabolite alterations in basal ganglia associated with methamphetamine-related psychiatric symptoms. A proton MRS study.

Following the chronic use of methamphetamine, some individuals experience psychosis and anxiety. One reason may be the persistence of metabolite abnormalities in the brain of currently abstinent former methamphetamine users. In this study, N-acetylaspartate (NAA), creatine plus phosphocreatine (Cr+PCr), and choline-containing compound (Cho) levels were measured in the left and right basal ganglia using proton magnetic resonance spectroscopy (MRS) in 13 abstinent methamphetamine users and 11 healthy comparison subjects with no history of illicit drug use. The methamphetamine users showed a significantly reduced Cr+PCr/Cho ratio in the bilateral basal ganglia compared with the healthy comparison subjects. Furthermore, the reduction in the Cr+PCr/Cho ratio was significantly correlated with the duration of methamphetamine use and with the severity of residual psychiatric symptoms. NAA/Cho ratios in the bilateral basal ganglia did not significantly differ between methamphetamine users and comparison subjects. These findings suggest that protracted use of methamphetamine may cause metabolite alterations in the basal ganglia. Furthermore, residual psychiatric symptoms may be attributable to the metabolite alterations in the basal ganglia.

Adult↗