Search PubMed⌕ Search

Biomedical subjects

Hiroshi Ujike

Publications and source records attributed to Hiroshi Ujike.

At least 19 recordsLinked to original sources
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

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

Association between the glutathione S-transferase M1 gene deletion and female methamphetamine abusers.

Several lines of evidence suggest that increased generation of auto-oxidized dopamine (DA) o-quinone is associated with the neurotoxicity of methamphetamine (MAP) in the brain, and that, as a cellular defenses against DA-derived quinines, glutathione S-transferase (GST) detoxifies auto-oxidized DA o-quinone in the brain. Glutathione S-transferase M1 (GSTM1) of the mu-class of GSTs catalyzes reaction between glutathione and catecholamine o-quinones under physiological conditions. This study was undertaken to investigate the role of the GSTM1 gene deletion polymorphism in the neuropathology of MAP abuse. One hundred fifty-seven MAP abusers and 200 healthy comparison subjects were tested for a genetic polymorphism of GSTM1. The difference in the frequency of deletion (D)/non-deletion (N) alleles between the female abusers and female controls was close to statistical significance (P = 0.071), although there was no statistical difference (P = 0.651) between male abusers and male controls. Furthermore, the number of female abusers with deletion alleles was significantly (P = 0.007, odds ratio: 2.77, 95% CI 1.30-5.89) higher than that of male abusers with deletion alleles. These findings suggest that GSTM1 gene deletion may contribute to a vulnerability to MAP abuse in female subjects, but not in male subjects.

Adult↗
PubMed2004

No association between the insulin degrading enzyme gene and Alzheimer's disease in a Japanese population.

Susceptibility to Alzheimer's disease (AD) is thought to be regulated by multiple genetic factors. Recently, three independent studies have reported that loci on chromosome 10q are linked with AD, and the insulin degrading enzyme (IDE; MIM 146680) gene located on chromosome 10q23-q25; IDE is located close to the maker D10S583, which exhibits a maximum LOD score for late-onset AD. We examined seven polymorphisms in the IDE gene, the marker D10S583 in the 5' flanking region, and SNPs in introns 1, 3, 11, 20, 21, and 22 (rs#1999764, 1855915, 1970244, 538469, 551266, and 489517, respectively). Four SNPs in introns 3, 11, 20, and 22 did not exhibit any polymorphisms in the Japanese population that was studied. D10S583 and two SNPs in introns 1 and 21 did not exhibit a significant association with early- or late-onset AD. In addition, no associations were observed for subgroups of AD grouped according to APOE status. The present study indicates that the IDE gene polymorphisms do not confer susceptibility to early- or late-onset AD at least in a Japanese population.

Aged↗
PubMed2004

Association of the Neprilysin gene with susceptibility to late-onset Alzheimer's disease.

Neprilysin (NEP), also known as neutral endopeptidase, enkephalinase, CD 10, and common acute lymphoblastic leukemia antigen, is a 97-kD protein. NEP can degrade amyloid beta peptides, and its mRNA and protein levels are known to be reduced in the brains of patients with Alzheimer's disease (AD), making the NEP gene a substantial candidate for an AD risk factor. We examined the genetic association of three NEP polymorphisms, a GT-repeat polymorphism and two single nucleotide polymorphisms (SNPs, -1075A>G and -1284G>C) in its promoter region, with AD in a Japanese case-control sample (240 patients and 163 controls). The GT-repeat polymorphism, but not the SNPs, was significantly associated with late-onset AD (p = 0.0007). Our findings suggest that the GT-repeat polymorphism in the promoter region of the NEP gene or some other unknown polymorphisms, which are in a linkage disequilibrium, confer a susceptibility to late-onset AD.

Age of Onset↗
PubMed2004

Neuronal expression of cyclooxygenase-2, a pro-inflammatory protein, in the hippocampus of patients with schizophrenia.

Several types of evidence suggesting that the inflammatory response system is associated with pathophysiology of schizophrenia have been accumulated. Recently, a prospective double-blind study demonstrated that supplementary treatment with celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, produced significantly greater improvement in scores on the Positive and Negative Syndrome Scale (PANSS) and on all subscales during the acute phase in patients with schizophrenia compared with risperidone alone therapy. The therapeutic effect of celecoxib on the psychopathology of schizophrenia is speculated to be based on COX activity inhibition; however, the detailed pharmacological mechanisms are unclear. To clarify whether or not COX-2 expression is altered in schizophrenia, we examined neuronal COX-2 expression in the hippocampus from cases of schizophrenia (n = 17), normal controls (n = 22), and cases of Alzheimer's disease (AD) as a positive control (n = 17). Quantitative immunohistochemical analysis demonstrated that neuronal COX-2 expression was significantly up-regulated in each CA1-4 region in Alzheimer's disease compared with controls, and that the mean COX-2 immunointensity in CA1-4 was significantly correlated with Abeta load in cases of Alzheimer's disease. In contrast, COX-2 expression was not up-regulated in any subdivision of the hippocampus in the schizophrenia group. These results suggest that celecoxib may affect the pathophysiology of schizophrenia through COX-2-independent actions rather than by inhibiting activity of up-regulated COX-2 protein.

Aged↗
PubMed2004

Pick's disease pathology of a missense mutation of S305N of frontotemporal dementia and parkinsonism linked to chromosome 17: another phenotype of S305N.

We report the second phenotype of frontotemporal dementia and parkinsonism linked to chromosome 17 with S305N similar to Pick's disease pathology in two brothers. The brain of the older brother showed macroscopic atrophy compatible with Pick's disease, and subsequent tau gene analysis revealed heterozygous S305N mutation in exon 10 of the tau gene. Round-shaped neuronal inclusions similar to Pick's bodies were positive for phosphorylated serine 262 as well as other anti-tau antisera, which is different from immunoexpression of Pick's bodies. Ultrastructurally, these neuronal inclusions consisted of straight, randomly orientated fibrils measuring approximately 10-20 nm in width and 60-600 nm in length. This ultrastructural profile is similar to that of the first case of S305N. S305N reported here can cause another phenotype closely resembling Pick's disease.

Asparagine↗
PubMed2004

[The human dihydropyrimidinase-related protein 2 (DRP-2) gene on chromosome 8p21 is associated with paranoid-type schizophrenia].

The dihydropyrimidinase-related protein (DRP) family, also called the collapsin response mediator protein, is implicated in the developmental process of the nervous system. Dysfunction of DRPs may result in neurodevelopmental abnormalities, which have been assumed to be a possible factor in the pathogenesis of schizophrenia. It has been reported that in humans, the expression of one member of the DRP family, DRP-2, is decreased in the brains of individuals with schizophrenia. In addition, the DRP-2 gene is located on chromosome 8p21, a region that has been implicated in schizophrenia in genetic linkage studies. We investigated a genetic association between five polymorphisms of the DRP-2 gene and schizophrenia in the Japanese population. The *2236T > C polymorphism in the 3' untranslated region (3'UTR) exhibited significant differences with respect to the distribution of the genotype and allele in patients compared with controls. The frequency of the *2236C allele was significantly higher in controls than in patients with schizophrenia (P = 0.0097) and patients with paranoid-type schizophrenia (P = 0.0083). These results suggest that the *2236C allele in the 3'UTR of the DRP-2 gene, or an unknown mutation in linkage disequilibrium with this allele, may reduce the susceptibility to schizophrenia, especially the paranoid subtype.

Alleles↗
PubMed2003

The human frizzled-3 (FZD3) gene on chromosome 8p21, a receptor gene for Wnt ligands, is associated with the susceptibility to schizophrenia.

Neurodevelopmental abnormalities have been reported in studies on the pathogenesis of schizophrenia. The Wnt-signaling pathway has been implicated in a variety of processes in neurodevelopment, and the frizzled proteins have been identified as receptors for Wnt ligands. Of the frizzled proteins, frizzled-3 (FZD3) is required for formation of the neural crest and for development of major fiber tracts in the CNS. The human FZD3 gene is located on chromosome 8p21, a positive linkage locus for schizophrenia. We analyzed polymorphisms of the FZD3 gene in patients with schizophrenia and control subjects in the Japanese population. We found a significant association between schizophrenia and the FZD3 gene in single nucleotide polymorphisms and haplotype analyses. Our data suggest that dysregulation of the Wnt-signaling pathway may be involved in the susceptibility to schizophrenia.

Adult↗
PubMed2003

No association between the sigma receptor type 1 gene and schizophrenia: results of analysis and meta-analysis of case-control studies.

BACKGROUND: Several lines of evidence have supported possible roles of the sigma receptors in the etiology of schizophrenia and mechanisms of antipsychotic efficacy. An association study provided genetic evidence that the sigma receptor type 1 gene (SIGMAR1) was a possible susceptibility factor for schizophrenia, however, it was not replicated by a subsequent study. It is necessary to evaluate further the possibility that the SIGMAR1 gene is associated with susceptibility to schizophrenia. METHODS: A case-control association study between two polymorphisms of the SIGMAR1 gene, G-241T/C-240T and Gln2Pro, and schizophrenia in Japanese population, and meta-analysis including present and previous studies. RESULTS: There was no significant association of any allele or genotype of the polymorphisms with schizophrenia. Neither significant association was observed with hebephrenic or paranoid subtype of schizophrenia. Furthermore, a meta-analysis including the present and previous studies comprising 779 controls and 636 schizophrenics also revealed no significant association between the SIGMAR1 gene and schizophrenia. CONCLUSION: In view of this evidence, it is likely that the SIGMAR1 gene does not confer susceptibility to schizophrenia.

Asian People↗
PubMed2003

No association between the dihydropyrimidinase-related protein 2 (DRP-2) gene and bipolar disorder in humans.

Several susceptibility loci for both of schizophrenia and bipolar disorder (BPD) have been found to overlap on several chromosomes including 8p21. Expression of dihydropyrimidinase-related protein 2 (DRP-2), which gene is located on 8p21, was found to be reduced in the brains of individuals with schizophrenia and BPD. Recently, we demonstrated a significant association between the DRP-2 gene and schizophrenia. Based on the rationale, we investigated the genetic association of the DRP-2 gene with BPD using a case-control study in the Japanese population. However, no significant associations were found between five polymorphisms of the DRP-2 gene (-975C>G, 352G>A, 426C>T, 1506T>C, and *2236T>C), and BPD, nor were associations detected between either of the polymorphisms and any subtype of BPD, bipolars I and II. The present study did not provide any evidence for a contribution of the DRP-2 gene to susceptibility to BPD.

Adult↗
PubMed2003

Association between a novel polymorphism in the promoter region of the neuropeptide Y gene and schizophrenia in humans.

Hypoactivity of neuropeptide Y (NPY) is thought to be involved in the pathophysiology of schizophrenia, because post-mortem brain studies revealed a decrease of the NPY in schizophrenia, and antipsychotic treatments increase the NPY in animal brains and in cerebrospinal fluid of patients. We performed genetic analysis of the NPY gene in schizophrenia. Mutation screening of the gene detected nine single nucleotide polymorphisms, of which we typed a -485C>T variation from potential functional relevance. The -485T allele was overly represented in the disease group (P=0.0043). An in vitro promoter assay revealed that a C to T change at nt -485 significantly reduced transcriptional activity. These results suggest that the -485T allele in NPY may confer susceptibility to schizophrenia by decreasing the neuropeptide in brains.

Genetic Predisposition to Disease↗
PubMed2003

Variability and heterogeneity in Alzheimer's disease with cotton wool plaques: a clinicopathological study of four autopsy cases.

We describe three cases of early- (cases 1-3, 28-39 years) and one of late-onset (case 4, 76 years) Alzheimer's disease (AD) with 'cotton wool' plaques (CWPs) but without a family history indicating autosomal dominant inheritance. The early-onset cases, but not the late-onset case, showed remarkable aggression, disinhibition, and impulsiveness. Spastic paraparesis was observed in only one early-onset case. Hematoxylin-eosin-stained sections showed numerous CWPs, especially in the temporal cortex, in all cases. Bielschowsky-stained sections showed neurofibrillary tangles and minor neuritic changes surrounding the CWPs in three cases, but not in case 2. Gallyas-Braak-stained sections showed weak argyrophilia in homogeneous material of the CWPs in cases 2 and 4. Quantitative analysis demonstrated that Abeta42 was deposited more predominantly than Abeta40 in three cases. However, in case 2, approximately twice as much Abeta40 as Abeta42 was deposited. Tau immunostaining demonstrated neuritic changes in three cases, but not in case 2. alpha-Synuclein-positive Lewy bodies (LBs) and astrocytic lesions containing non-Abeta component of AD amyloid (NAC), a central fragment of alpha-synuclein, were found in case 3. In conclusion, (1) a frontal lobe syndrome-like personality change may be one of the characteristic clinical features of early-onset CWP-AD, (2) the deposition pattern of Abeta40 and Abeta42 in CWP-AD is more variable than that of presenilin-1-linked cases, (3) Abeta deposition can result in development of dementia without tau pathology, and (4) CWP-AD with LBs and several other neurodegenerative disorders with LBs share a common process involving alpha-synuclein and NAC deposition.

Adult↗
PubMed2003

Cyclooxygenase-2 in the hippocampus is up-regulated in Alzheimer's disease but not in variant Alzheimer's disease with cotton wool plaques in humans.

We examined neuronal expression of cyclooxygenase-2, a pro-inflammatory protein, and neuron densities in the CA1-4 of the hippocampus in three cases of Alzheimer's disease with cotton wool plaques (CWP-AD), 17 cases of typical Alzheimer's disease without CWPs (tAD), and 26 normal controls. Cyclooxygenase-2 expression was significantly increased in all of the CA1-4 in tAD, but not in any subdivision in CWP-AD, compared with controls. Cyclooxygenase-2 expression in tAD was also significantly up-regulated compared with that in CWP-AD in all subdivisions. Furthermore, neuron density in the hippocampus was not significantly reduced in CWP-AD cases compared with controls despite remarkable intra- and extraneuronal Abeta deposition. These findings suggest that unknown factors besides Abeta deposition are necessary for the cyclooxygenase-2 up-regulation and neurodegeneration in Alzheimer's disease.

Aged↗
PubMed2003

The human dihydropyrimidinase-related protein 2 gene on chromosome 8p21 is associated with paranoid-type schizophrenia.

BACKGROUND: The dihydropyrimidinase-related protein (DRP) family, also called the collapsin response mediator protein, is implicated in the developmental process of the nervous system. Dysfunction of DRPs may result in neurodevelopmental abnormalities, which may be a factor in the pathogenesis of schizophrenia. The expression of one member of DRP-2 in humans has been reported to be decreased in the brains of people with schizophrenia. In addition, the DRP-2 gene (Dihydropyrimidinase-like 2; DPYSL2) is located on chromosome 8p21, a region that has been implicated in schizophrenia in genetic linkage studies. METHODS: We investigated a genetic association between five polymorphisms of the DRP-2 gene and schizophrenia in the Japanese population. RESULTS: The *2236T>C polymorphism in the 3' untranslated region (3'UTR) exhibited significant differences with respect to the distribution of the genotype and allele in patients compared with control subjects. The frequency of the *2236C allele was significantly higher in control subjects than patients with schizophrenia (p =.0097) and paranoid-type schizophrenia (p =.0083). CONCLUSIONS: Our results suggest that the *2236C allele in the 3'UTR of the DRP-2 gene, or an unknown mutation in linkage disequilibrium with this allele, may reduce the susceptibility to schizophrenia, especially the paranoid subtype.

Alleles↗
PubMed2003

Association study of the brain-derived neurotrophic factor (BDNF) gene with bipolar disorder.

Brain-derived neurotrophic factor (BDNF) belongs to a family of neurotrophic factors and has been demonstrated to promote the survival, differentiation, and maintenance of a broad variety of central nervous system neurons. Several reports have suggested that the BDNF gene is a plausible functional candidate gene underlying the predisposition for developing bipolar disorder (BPD). In the present study, we investigated the possible role of the BDNF gene in the etiology of BPD using a matched case-control association design in a Japanese population. There was no evidence for an allelic or genotypic association of two polymorphisms (-1360C>T and 196G>A) of the BDNF gene with BPD. Furthermore, no significant association was observed between these polymorphisms and either of two diagnostic subtypes (bipolars I and II disorder). The results suggest that the BDNF gene is unlikely to confer susceptibility to BPD.

Bipolar Disorder↗
PubMed2003

Association study between the fibronectin gene and schizophrenia.

Fibronectin is one of the cell adhesion proteins. Adhesion molecules play an important role in neural and synaptic genesis, and their dysfunction may result in neurodevelopmental abnormalities, which have been assumed to be a factor in the pathogenesis of schizophrenia. To examine the possible involvement of fibronectin in the etiology of schizophrenia, we analyzed six polymorphisms, located in introns 2, 21, 24, and 26, and exons 20 and 28, in the human fibronectin gene (FN1) of schizophrenic patients in the Japanese population (n = 104) and age-and gender-matched controls (n = 104). No significant positive association was observed between either of the polymorphisms and schizophrenia, nor was an association found between either of the polymorphisms and any subtypes of schizophrenia. These data did not provide evidence for a contribution of the FN1 gene to susceptibility to schizophrenia.

Adult↗