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Kazuo Yamada

Publications and source records attributed to Kazuo Yamada.

At least 55 records · Page 3Linked to original sources
PubMed2005

Expression of myelencephalon-specific protease after cryogenic lesioning of the rat parietal cortex.

The gene for myelencephalon-specific protease (MSP) is a member of the kallikrein gene family and in rats is expressed mainly in the central nervous system. Its function and alteration in brain injury have not yet been clarified. We examined the expression of MSP after cryogenic injury (CI) using in situ hybridization, immunohistochemistry, and Western blotting. Analysis of MSP mRNA by in situ hybridization revealed a higher level of expression around the cryogenic area than on the contralateral side at 2-7 days after CI, with peak expression occurring 7 days after CI. Immunohistochemical analysis demonstrated expression of MSP protein at 1 day after CI, in the same region in which MSP mRNA was observed, with peak expression again at 7 days after CI, in the area around the lesion. Double immunohistochemical labeling revealed that MSP was expressed mainly in oligodendrocytes. These results suggest that expression of MSP may be related to the turnover of myelin-associated proteins and extracellular matrix proteins after CI. The regulation of active MSP may be important in the physiological or pathological changes involved in remyelination or demyelination.

Animals↗
PubMed2005

Oral administration of geranylgeranylacetone improves survival rate in a rat endotoxin shock model: administration timing and heat shock protein 70 induction.

The present study was performed to determine whether oral pretreatment with geranylgeranylacetone (GGA) inhibits proinflammatory cytokine liberation and nitric oxide (NO) production in lipopolysaccharide (LPS)-treated rats and protects rats against death from LPS-induced endotoxin shock, and whether such protection by GGA is related to heat shock protein (HSP) 70 induction in multiple organs of rats. GGA (200 mg/kg) was given orally to rats. LPS (20 mg/kg) was administered intraperitoneally 4, 8, 16, or 24 h after GGA administration. The survival of rats was monitored over 24 h after LPS administration. GGA treatment at 8 or 16 h before LPS dramatically improved the survival rate of LPS-treated rats. Plasma levels of proinflammatory cytokines (tumor necrosis factor-alpha and interleukin-6) and NO 6 h after LPS administration in these GGA-pretreated rats were less than one-half of those in rats treated with LPS alone. A GGA challenge 8 or 16 h before LPS administration enhanced HSP70 expression in rat organs after LPS. Treatment with GGA 8 h before LPS minimized hepatic and renal damage. Furthermore, the protective effect of GGA on mortality in LPS-treated rats was inhibited with quercetin, known as an HSP70 inhibitor. These results suggest that oral administration of GGA at an optimal time before LPS injection induces and enhances HSP70 expression in several organs, inhibits proinflammatory cytokine and NO production, and prevents organ damage, resulting in an improved survival rate.

Administration, Oral↗
PubMed2005

Effectiveness of herbal medicine (Rokumigan and Hachimijiogan) for fatigue or loss of energy in patients with partial remitted major depressive disorder.

Some patients with major depressive disorder (MDD) do not show remission of their depressive symptomatology. We investigated the efficacy of Rokumigan (TJ-87) and Hachimijiogan (TJ-7) in 20 patients with prolonged partial remitted MDD associated with fatigue or loss of energy. In these 20 patients, TJ-7 or TJ-87 was added to the previous regimen for 4 weeks. Six patients were 'much improved', six were 'minimally improved' (responders), and eight showed 'no change' (non-responders), on the Clinical Global Impression Global Improvement scale. All responders had Shofuku-fujin (tenderness or weakness of the lower abdomen). In conclusion, we experienced 12 outpatients with prolonged partial remitted MDD with fatigue or loss of energy, which was successfully treated with TJ-87 or TJ-7.

Adult↗
PubMed2005

Successively postadministered melatonin prevents disruption of hepatic antioxidant status in rats with bile duct ligation.

We have reported that orally administered melatonin exerts a therapeutic effect on cholestatic liver injury in rats treated with bile duct ligation (BDL) possibly through its antioxidant and anti-inflammatory actions. Herein, we examined whether successively postadministered melatonin prevents the disruption of hepatic antioxidant status in BDL-treated rats. Wistar rats with BDL were killed 5 and 13 days after BDL. Melatonin (10 or 100 mg/kg body weight) was orally administered to rats with and without BDL everyday for 8 days, starting 5 days after BDL. The hepatic concentrations of thiobarbituric acid reactive substances, an index of lipid peroxidation, and reduced glutathione increased 5 days after BDL and further increased at 13 days. Hepatic vitamin E concentration and catalase and Se-glutathione peroxidase (Se-GSH-Px) activities were similarly reduced at 5 and 13 days after BDL. Hepatic ascorbic acid concentration and the hepatic activities of Cu,Zn- and Mn-superoxide dismutases, glutathione reductase, and glucose-6-phosphate dehydrogenase decreased 13 days after BDL. Melatonin postadministered to BDL-treated rats attenuated all these changes observed at 13 days after the treatment more effectively at the higher dose than at the lower dose. Melatonin administered to BDL-untreated rats increased the hepatic Se-GSH-Px activity at both doses and the hepatic activities of Cu,Zn- and Mn-superoxide dismutases at the higher dose. These results indicate that successively postadministered melatonin at pharmacological doses prevents the disruption of hepatic antioxidant status in rats with BDL through its direct and indirect antioxidant action, which may contribute to its therapeutic effect of BDL-induced cholestatic liver injury.

Animals↗
PubMed2005

[Brain edema and aquaporin].

Aquaporin is a membrane-bound water channel and highly related to the development and resolution of brain edema. We have detected mRNA and protein expression of aquaporin-4 in ischemic and traumatic brain injury. The aquaporin-4 expression is related to the resolution of brain edema rather than the evolution of the edema. We also detected the relation of aquaporin-1 expression and the evolution of hydrocephalus. Regulation of aquaporin function may be a new venue of treatment in brain edema.

Animals↗
PubMed2004

Association analysis of FEZ1 variants with schizophrenia in Japanese cohorts.

BACKGROUND: DISC1 has been suggested as a causative gene for psychoses in a large Scottish family. We recently identified FEZ1 as an interacting partner for DISC1. To investigate the role of FEZ1 in schizophrenia and bipolar disorder, case-control association analyses were conducted in Japanese cohorts. METHODS: We performed a mutation screen of the FEZ1 gene and detected 15 polymorphisms. Additional data on informative polymorphisms were obtained from public databases. Eight single nucleotide polymorphisms (SNPs) were analyzed in 119 bipolar disorder and 360 schizophrenic patients and age- and gender-matched control subjects. All genotypes were determined with the TaqMan assay, and selected samples were confirmed by sequencing. RESULTS: The two adjacent polymorphisms displayed a nominally significant association with schizophrenia (IVS2+ 1587G>A, p = .014; 396T<A or Asp123Glu, p = .024). Homozygotes with the Glu123 allele were observed in only a small portion (2%) of schizophrenia patients but not in control subjects or bipolar patients. Conversely, no SNPs displayed allelic, genotypic, or haplotypic associations with bipolar disorder. CONCLUSIONS: A modest association between FEZ1 and schizophrenia suggests that this gene and the DISC1-mediated molecular pathway might play roles in the development of schizophrenia, with FEZ1 affecting only a small subset of Japanese schizophrenia patients.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Deficiency of theory of mind in patients with remitted mood disorder.

BACKGROUND: Recent researches on theory of mind (ToM) in patients with mood disorders have revealed deficits of ToM ability during episodes. In this study, we aimed to test ToM ability among patients with unipolar or bipolar depression currently in remission. METHODS: ToM ability and IQ obtained by Wechsler Adult Intelligence Scale-Revised (WAIS-R) were evaluated in 50 patients with remitted depression, who met the criteria of mood disorders of DSM-IV, and 50 matched healthy controls. RESULTS: The patients with mood disorders showed statistically significant impairment in a second-order false question (Fisher's Exact Test p < 0.0001). No significant difference was shown in the other three areas of ToM between the patients and the controls. In addition, no correlation of the four areas of ToM with IQ obtained by WAIS-R was found. LIMITATIONS: The relation of ToM deficit to other specific cognitive impairment was not examined. CONCLUSIONS: Our results suggest that depressive patients in symptomatic remission have a lower ability of second-order false belief. The ToM impairment suggests a decline of skillful social relationships. Evaluation of ToM ability in depressive patients in remission may be useful to provide treatment for better social adjustment.

Adolescent↗
PubMed2004

Association of mitochondrial complex I subunit gene NDUFV2 at 18p11 with bipolar disorder in Japanese and the National Institute of Mental Health pedigrees.

BACKGROUND: Linkage with 18p11 is one of the replicated findings in molecular genetics of bipolar disorder. Because mitochondrial dysfunction has been suggested in bipolar disorder, NDUFV2 at 18p11, encoding a subunit of the complex I, reduced nicotinamide adenine dinucleotide (NADH)ubiquinone oxidoreductase, is a candidate gene for this disorder. We previously reported that a polymorphism in the upstream region of NDUFV2, -602G> A, was associated with bipolar disorder in Japanese subjects; however, functional significance of -602G> A was not known. METHODS: We screened the further upstream region of NDUFV2. We performed a case-control study in Japanese patients with bipolar disorder and control subjects and a transmission disequilibrium test in 104 parent and proband trios of the National Institute of Mental Health (NIMH) Genetics Initiative pedigrees. We also performed the promoter assay to examine functional consequence of the -602G> A polymorphism. RESULTS: The -602G> A polymorphism was found to alter the promoter activity. We found that the other haplotype block surrounding -3542G> A was associated with bipolar disorder. The association of the haplotypes consisting of -602G> A and -3542G> A polymorphisms with bipolar disorder was seen both in Japanese case-control samples and NIMH trios. CONCLUSION: Together these findings indicate that the polymorphisms in the promoter region of NDUFV2 are a genetic risk factor for bipolar disorder by affecting promoter activity.

Adult↗
PubMed2004

Association study of polymorphisms in the 5' upstream region of human DISC1 gene with schizophrenia.

Disrupted-in-Schizophrenia-1 (DISC1) is a gene in which a mutant truncation by a balanced t(1;11)(p42.1;q14.3) translocation is segregated with major psychiatric illness with a predominance of schizophrenic symptomatology in a large Scottish family. However, no functional polymorphisms have been detected that are associated with schizophrenia in general populations. As prior polymorphism searches in DISC1 have been focused on coding exons and flanking introns, the present study examined sequence variations in the 5' upstream region of DISC1. Screening of exon 1 through to approximately 1.0 kb upstream of exon 1 identified 6 polymorphisms, including 2 novel variants, -94C>A and -199(CG)(n). We tested these variants for associations with schizophrenia in the first set of a case (n = 198) and control (n = 198) panel, and found significant results with -274G>C (genotypic P = 0.01) and -215(TG)(n) (genotypic P = 0.039). However, we failed to replicate these associations in a second, larger independent patient (n = 532) and control (n = 519) sample. These results suggest that the genomic interval of DISC1 probably involved in transcriptional regulation does not display major genetic relevance in Japanese schizophrenia patients.

5' Flanking Region↗
PubMed2004

Genetic and expression analyses of FZD3 in schizophrenia.

BACKGROUND: Wnt signaling plays important roles in neurodevelopmental processes. Frizzled is a receptor of Wnt protein, and the Frizzled 3 (FZD3) gene was recently reported to be associated with schizophrenia. Our study attempted to confirm associations between FZD3 and schizophrenia in Japanese family and case-control samples. METHODS: Genetic associations were evaluated using family-based transmission tests (212 families, 643 subjects) and case--control analysis (540 schizophrenia patients, 540 control sample). Six single nucleotide polymorphisms (SNPs) on the FZD3 locus were genotyped, and levels of FZD3 mRNA expression in postmortem brains were examined. RESULTS: Neither family- nor population-based studies supported associations between FZD3 and schizophrenia. FZD3 expression was unaltered in schizophrenic brains. CONCLUSIONS: Although two prior studies have reported associations using limited numbers of SNPs on FZD3, our intensive study failed to support any major contribution of FZD3 to schizophrenia susceptibility.

Adult↗
PubMed2004

No association between the Val66Met polymorphism of the brain-derived neurotrophic factor gene and bipolar disorder in a Japanese population: a multicenter study.

BACKGROUND: Two previous studies reported a significant association between a missense polymorphism (Val66Met) in the brain-derived neurotrophic factor (BDNF) gene and bipolar disorder; however, contradictory negative results have also been reported, necessitating further investigation. METHODS: We organized a multicenter study of a relatively large sample of 519 patients with bipolar disorder (according to DSM-IV criteria) and 588 control subjects matched for gender, age, and ethnicity (Japanese). Genotyping was done by polymerase chain reaction-based restriction fragment length polymorphism or direct sequencing. RESULTS: The genotype distributions and allele frequencies were similar among the patients and control subjects. Even if the possible relationships of the polymorphism with several clinical variables (i.e., bipolar I or II, presence of psychotic features, family history, and age of onset) were examined, no variable was related to the polymorphism. CONCLUSIONS: The Val66Met polymorphism of the BDNF gene is unrelated to the development or clinical features of bipolar disorder, at least in a Japanese population.

Adult↗
PubMed2004

Expression of myelencephalon-specific protease in transient middle cerebral artery occlusion model of rat brain.

Myelencephalon-specific protease (MSP) is one of the serine proteases and is expressed in the central nervous system of rats. Its function and alternation in brain injury have not yet been clarified. In this study, we investigated the expression of MSP after transient middle cerebral artery occlusion (MCAO) using in situ hybridization and immunohistochemistry. In situ localization of MSP mRNA demonstrated a higher level in the corpus callosum and around the ischemic area from 12 h to 14 days after MCA reperfusion, with the peak of expression coming 3 days after reperfusion in both regions. Immunohistochemically, the expression of protein was found 1 day after reperfusion in the same brain region that was observed for mRNA. The peak was 7 days after reperfusion in both regions. Micro-autoradiography, immunostaining and double immunohistochemical labeling revealed the expression of MSP to be located mainly in the oligodendrocytes. The present results indicate that MSP may be related to the turnover of the myelin-associated proteins and the extracellular matrix proteins after transient MCAO. The activation of MSP may play a role in remodeling processes such as neurite outgrowth and remyelination.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed2004

Association of neural cell adhesion molecule 1 gene polymorphisms with bipolar affective disorder in Japanese individuals.

BACKGROUND: Although the pathogenesis of mood disorders remains unclear, heritable factors have been shown to be involved. Neural cell adhesion molecule 1 (NCAM1) is known to play important roles in cell migration, neurite growth, axonal guidance, and synaptic plasticity. Disturbance of these neurodevelopmental processes is proposed as one etiology for mood disorder. We therefore undertook genetic analysis of NCAM1 in mood disorders. METHODS: We determined the complete genomic organization of human NCAM1 gene by comparing complementary deoxyribonucleic acid and genomic sequences; mutation screening detected 11 polymorphisms. The genotypic, allelic, and haplotype distributions of these variants were analyzed in unrelated control individuals (n = 357) and patients with bipolar disorder (n = 151) and unipolar disorder (n = 78), all from central Japan. RESULTS: Three single nucleotide polymorphisms, IVS6+32T>C, IVS7+11G>C and IVS12+21C>A, displayed significant associations with bipolar disorder (for allelic associations, nominal p =.04, p =.02, and p =.004, respectively, all p >.05 after Bonferroni corrections). Furthermore, the haplotype located in a linkage disequilibrium block was strongly associated with bipolar disorder (the p value of the most significant three-marker haplotype is .005). CONCLUSIONS: Our results suggest that genetic variations in NCAM1 or nearby genes could confer risks associated with bipolar affective disorder in Japanese individuals.

Adult↗
PubMed2004

Potential roles of hepatic heat shock protein 25 and 70i in protection of mice against acetaminophen-induced liver injury.

The aim of the present study was to assess the contribution of the level of expression of heat shock protein 25 (HSP25), 60 (HSP60), 70 (HSC70) and 70i (HSP70i) in mouse livers after a lethal dose of acetaminophen (APAP) to their survival. We examined changes in survival ratio, plasma APAP level and alanine aminotransferase (ALT) activity, and hepatic reduced glutathione (GSH), HSP25, HSP60, HSC70 and HSP70i levels following treatment of mice with APAP (500 mg/kg, p.o.). The plasma APAP level increased rapidly, and reached a maximum 0.5 h after APAP treatment. Hepatic GSH decreased rapidly, and was almost completely depleted 1 h after APAP treatment. Plasma ALT activity, an index of liver injury, significantly increased from 3 h onwards after APAP treatment. The survival ratios 9 h, 24 h and 48 h after APAP treatment were 96%, 38% and 36%, respectively. We found a remarkable difference in the patterns of hepatic HSP25 and HSP70i induction in mice that survived after APAP treatment. HSP70i levels increased from 1 h onwards after APAP treatment in a time-dependent manner, and reached a maximum at 9 h. In contrast, HSP25 could be detected just 24 h after APAP treatment, and maximal accumulation was observed at 48 h. Other HSPs examined were unchanged. Notably, the survival ratio dropped by only 2% after HSP25 expression. Recently, a novel role for HSP25 as an anti-inflammatory factor was suggested. We have already shown that 48-h treatment with APAP induces severe centrilobular necrosis with inflammatory cell infiltration in mouse livers. Taken together, the level of expression of hepatic HSP25 may be a crucial determinant of the fate of mice exposed to APAP insult.

Acetaminophen↗
PubMed2004

Association between schizophrenia with ocular misalignment and polyalanine length variation in PMX2B.

The increased incidence of minor physical anomalies (MPAs) in schizophrenia is the fundamental basis for the neurodevelopmental hypothesis of schizophrenia etiology. Ocular misalignment, or strabismus, falls into the category of MPAs, but this phenotype has not been assessed in schizophrenia. This study reveals that a subtype of strabismus, constant exotropia, displays marked association with schizophrenia (P=0.00000000906). To assess the genetic mechanisms, we examined the transcription factor genes ARIX (recently identified as a causative gene for syndromic strabismus) and its paralogue, PMX2B. We identified frequent deletion/insertion polymorphisms in the 20-alanine homopolymer stretch of PMX2B, with a modest association between these functional polymorphisms and constant exotropia in schizophrenia (P=0.029). The polymorphisms were also associated with overall schizophrenia (P=0.012) and more specifically with schizophrenia manifesting strabismus (P=0.004). These results suggest a possible interaction between PMX2B and other schizophrenia-precipitating factors, increasing the risk of the combined phenotypes. This study also highlights the unique nature of the polyalanine length variations found in PMX2B. In contrast with other transcription factor genes, the variations in PMX2B show a high prevalence, with deletions being more common than insertions. Additionally, the polymorphisms are of ancient origin and stably transmitted, with mild phenotypic effects. In summary, our study lends further support to the disruption of neurodevelopment in the etiology of schizophrenia, by demonstrating the association of a specific MPA, in this case, constant exotropia with schizophrenia, along with molecular variations in a possible causative gene.

Base Sequence↗