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Biomedical subjects

K Ikari

Publications and source records attributed to K Ikari.

18 recordsLinked to original sources
PubMed2006

Haplotype analysis revealed no association between the PTPN22 gene and RA in a Japanese population.

OBJECTIVE: The protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene is a member of the PTPs that negatively regulate T-cell activation. A missense single nucleotide polymorphism (SNP) in the PTPN22 gene known as R620W was recently reported to be associated with several autoimmune diseases including rheumatoid arthritis (RA). The association was confirmed repeatedly in the populations of North European ancestry. However, the SNP was reported to be non-polymorphic in the Asian populations. Because the gene confers an impact on autoimmune diseases, we attempt to explore an association between PTPN22 gene and RA in a Japanese population without restricting to the SNP, R620W. METHODS: We studied 1128 RA patients and 455 controls. In addition to the SNP, R620W, we selected eight testing SNPs spanning 45 kb over the PTPN22 gene using the International HapMap Project. Genotyping was performed using the TaqMan fluorogenic 5' nuclease assay. Associations between RA and each of the SNPs were estimated by the Fisher's exact test. Haplotype was constructed using the expectation-maximization algorithm. RESULTS: R620W was not polymorphic enough in both the patients and the controls, and was therefore excluded from further analysis. Each allele frequency for the eight other SNPs in both groups was compared and no association was detected. Haplotype analysis also revealed that PTPN22 gene was not associated with RA in a Japanese population. CONCLUSION: We found no association between PTPN22 and RA in a Japanese population. The result suggests that the PTPN22 gene is associated with RA only in a specific ethnic group.

Arthritis, Rheumatoid↗
PubMed2006

Association between PADI4 and rheumatoid arthritis: a meta-analysis.

OBJECTIVE: Polymorphisms and haplotypes of the peptidylarginine deiminase type 4 gene (PADI4) have been reported to be associated with rheumatoid arthritis (RA) in a Japanese population. However, subsequent replication studies showed conflicting results. The aim of this study was to determine whether meta-analysis would prove the existence of the association. METHODS: PubMed was searched using the term 'PADI4' for articles from the publication of the first study to December 2005. Replication studies that tested the association between PADI4 and RA were reviewed for meta-analysis. The Breslow-Day test for homogeneity across the studies was calculated. The Mantel-Haenszel procedure was used to pool odds ratios (OR) with 95% confidence intervals (CI) to evaluate the association. RESULTS: Six replication studies, one from Japan and five from Europe and North America, fulfilled the selection criteria for inclusion in the meta-analysis. Homogeneity was confirmed across the replication studies. The common OR was 1.14 (95% CI = 1.07-1.21) for allelic distribution. The association was confirmed when only five replication studies in the European descent populations were combined (P = 0.0096, common OR = 1.10). CONCLUSIONS: Our meta-analysis showed a positive association between PADI4 and RA not only in the Japanese population but also in populations of European descent.

Arthritis, Rheumatoid↗
PubMed2005

Supportive evidence for a genetic association of the FCRL3 promoter polymorphism with rheumatoid arthritis.

BACKGROUND: An association between susceptibility to rheumatoid arthritis and the Fc receptor-like 3 gene (FCRL3) has been reported in a Japanese population. A case-control study showed that the strongest evidence of the association was derived from a polymorphism in the promoter region of FCRL3, which has a regulatory effect on the expression of the gene. OBJECTIVE: To validate the findings of this previous report by examining the -169C-->T single nucleotide polymorphism (SNP) in a large cohort. METHODS: 752 unrelated cases and 940 controls were genotyped. All the samples were from the same ethnic background as the original study. Genotyping was done using 5' allelic discrimination assays. Association between susceptibility to rheumatoid arthritis and -169C-->T SNP was examined by chi(2) testing. RESULTS: As in the previous study, the SNP showed significant differences between cases and controls (p = 0.022, odds ratio = 1.18, 95% confidence interval 1.02 to 1.35). CONCLUSIONS: This result supports a genetic association of the FCRL3 promoter polymorphism with rheumatoid arthritis.

Arthritis, Rheumatoid↗
PubMed2001

Establishment of an optimized set of 406 microsatellite markers covering the whole genome for the Japanese population.

Microsatellites, an essential tool for genetic linkage analyses, are selected in genetic studies on the basis of both informativeness and their positions with respect to one another on the genetic map. In order to establish a microsatellite marker set useful for linkage studies in the Japanese population, we first genotyped 64 unrelated Japanese subjects, using 400 microsatellite markers from a commercially available set (ABI PRISM Linkage Mapping Set-MD10) and then determined the allelic frequencies and heterozygosities for these marker loci in the population. In order to optimize the set, we replaced 41 markers having a heterozygosity lower than 0.6 with as many informative markers in the corresponding loci, and newly added six markers in the set to minimize the several gaps found at intervals of over 20 cM. We finally established a set comprising 406 microsatellites with average intervals of 9cM (maximum, 17 cM) and minimum heterozygosities of over 0.6 (mean, 0.76). All data generated in this study, including the specific polymerase chain reaction (PCR) primer sequences of the newly added markers, are freely available to all researchers at our web site. The genetic tool established here should facilitate genetic linkage studies of various hereditary diseases, especially in the Japanese.

Alleles↗
PubMed2001

Gender-specific haplotype association of collagen alpha2 (XI) gene in ossification of the posterior longitudinal ligament of the spine.

Among Japanese, ossification of the posterior longitudinal ligament of the spine (OPLL) is a leading cause of myelopathy, showing ectopic bone formation in the paravertebral ligament. We have provided genetic evidence that the collagen alpha2 (XI) (COL11A2) locus of chromosome 6 constitutes susceptibility for OPLL. Five distinct single nucleotide polymorphisms (SNPs), identified in COL11A2, were combined to construct possible haplotypes by the use of a maximum likelihood program. Estimated haplotype frequency was compared in OPLL patients and non-OPLL controls. We report a gender-specific association of the COL11AA2 haplotvpe with OPLL. The frequency of the most commonly observed haplotype was significantly higher in male patients (P = 0.0003) compared with controls, but not in female patients (P = 0.21). OPLL is predominantly observed in males. with a prevalence ratio of 2:1, and our gender-specific associations indicate that genetic factors involving COL11A2 play a specific role in the etiology of OPLL exclusively in males.

Aged↗
PubMed2001

Functional impact of human collagen alpha2(XI) gene polymorphism in pathogenesis of ossification of the posterior longitudinal ligament of the spine.

Ossification of the posterior longitudinal ligament (OPLL) of the spine is the leading cause of myelopathy in Japan. In earlier studies, we provided genetic linkage and allelic association evidence of distinct differences in the human collagen alpha2(XI) gene (COL11A2) that might constitute inherited predisposition to OPLL. In the present study, a strong allelic association with non-OPLL (p = 0.0003) was observed with an intron 6 polymorphism [intron 6 (-4A)], in which the intron 6 (-4A) allele is more frequently observed in non-OPLL subjects than in OPLL patients. In addition, a newly identified polymorphism in exon 6 [exon 6 (+28A)] was in linkage disequilibrium with the intron 6 (-4A). The functional impact of the polymorphisms was analyzed by comparing the differences in messenger RNA (mRNA) splicing by reverse-transcription polymerase chain reaction (RT-PCR) analysis in cultured cells from the interspinous ligament and an in vitro exon trapping study. The intron 6 (-4A) allele resulted in skipping exon 6 and retaining exon 7, while the exon 6 (+28A) allele was not associated with alteration in mRNA splicing. Similar mRNA species were observed in undifferentiated osteoblast (Ob) cells and in cells from posterior longitudinal ligament of non-OPLL subjects. The region containing exons 6-8 is an acidic subdomain presumably exposed to the surface that could interact with molecules of the extracellular matrix. Accordingly, retaining exon 7 together with removal of exon 6 observed in intron 6 (-4A) could play a protective role in the ectopic ossification process because the same pattern was observed in undifferentiated Ob cells and nonossified posterior longitudinal ligament cells.

Alternative Splicing↗
PubMed1985

Relationship between sibship size and neurotic symptoms of anxiety, hypochondriasis and depression in Japanese neurotic children and adolescents.

Two hundred and sixty-eight Japanese aged 19 or below were studied retrospectively from their medical records to determine the relationship between the sibship size (number of siblings in the family) and the appearance of symptoms of anxiety, hypochondriasis and depression during the time period I (1955 + 1960 + 1965) and the time period II (1970 + 1975 + 1978). The results showed that only sons and either sex of a large sibship size (4 or more) possessed these three symptoms to a larger extent than only daughters and either sex of a medium sibship size (2 or 3) during both time periods. These three adult-type neurotic symptoms were thought to be manifested among the children and adolescents who communicated primarily with adults and/or those who were required by their parents to exhibit adult-type behavior whether in traditional or in modern Japanese families.

Adolescent↗
PubMed1984

Familial occurrence of adult-type neuronal ceroid lipofuscinosis.

The adult type of neuronal ceroid lipofuscinosis (NCL) occurred in a 49-year-old man and his 51-year-old sister. They showed episodic stuporous and psychotic states, mental retardation, generalized convulsions, and ichthyosis vulgaris. At autopsy the woman had excessive accumulation of lipofuscin throughout the CNS. The degree of neuronal lipopigment accumulation was very severe in the neurons of the thalamus, substantia nigra, inferior olivary nuclei, motor nuclei of the brain stem, and cerebral cortex. Mental symptoms, such as stupor, excitement, hallucinations, and delusions, were the predominant clinical manifestations and so were misdiagnosed as schizophrenia. Though the clinical diagnosis of the adult type of NCL (Kufs' disease) is difficult because of its wide variety of manifestations, symptoms such as episodic psychotic and stuporous states accompanied by convulsive disorders with mild neurologic signs may be an indication of this disease.

Age Factors↗
PubMed1984

Age-related changes in the Purkinje's cells in the rat cerebellar cortex: a quantitative electron microscopic study.

The present study was undertaken to assess age-related changes in the Purkinje's cells in the rat cerebellar cortex. The cellular and nucleolar volumes and the volume percentage of lipofuscin per cytoplasma were measured in six age groups. The number of Purkinje's cells was also counted. The cellular volume of rats aged 18, 24 and 30 months decreased significantly as compared with that of 3-month-old rats. The nucleolar volume of rats aged 12, 18, 24 and 30 months decreased significantly as compared with that of 3-month-old rats. The accumulation of lipofuscin in the cytoplasma of the Purkinje's cells was observed more or less in all ages. The degree of accumulation of lipofuscin in the Purkinje's cells increased with aging. The number of Purkinje's cells at the ages of 24 and 30 months decreased significantly as compared with that of 3-month-old rats.

Aging↗
PubMed1983

An ultrastructural change in developing rat cerebral cortex: a morphometrical study.

Five age groups, each composed of four animals from each of the following ages, were used to assess age-related ultrastructural changes with development in the neuropil of the III layer of the frontal cortex (area 6) in rats; 1, 2, 3, 5 and 12 weeks old. Random samplings within the neuropil were taken to produce 25 electron micrographs in each rat (totaling 500). The profiles of axon terminals, dendrites and mitochondria in each element in the neuropil of each micrograph were traced. The percentage of their areas for the area of neuropil (relative volume fraction) was examined using the image analyzer system. The size and number of synaptic terminals were counted. The relative volume fractions of both the axon terminals and mitochondria in the terminals for the neuropil were found to have increased in the mature rats. On the other hand, the relative volume fraction of dendrites for the neuropil had been unchanged and the size of the terminals had gradually decreased. The number of terminals had progressively increased with development.

Animals↗
PubMed1982

Age-related changes in the neuropil in the rat inferior olive nucleus: quantitative electron microscopic study.

Age-related ultrastructural changes in the neuropil in the rat inferior olive nucleus were examined at 3, 6, 12, 18, 24 and 30 months old. The profiles of axon terminals, dendrites and astroglial processes from random samplings within the neuropil were traced. Subsequently, the percentages of these profiled areas in relation to the area of neuropil (relative volume fraction) were examined using the image analyzer system. The relative volume fractions of both axon terminals and dendrites in relation to the neuropil were found to have decreased in the aged rats, while the relative volume fraction of astroglial processes had progressively increased with aging.

Aging↗
PubMed1982

Terminal degeneration in the lateral septum of the rat after suprachiasmatic nucleus lesion.

Nerve terminals in the lateral septum were studied by electron microscopy in the rat after lesions of the suprachiasmatic nuclei (SCN). The results were as follows: 1) The electron-lucent degenerations showed a reduction in the number of vesicles and the swelling of terminals and/or vesicles. These degenerating terminals predominated at two days of survival period. The electron-dense degenerations which showed a darkening and shrinkage of the terminals mainly appeared at four days of survival period. 2) Most of the degenerating terminals contained large core vesicles of a diameter in the range of 800-1500 A. 3) The percentage of the degenerating terminals to all the terminals on the electron micrographs was about 7%. 4) The F-type synapses were not found in the lateral septum of the normal and SCN lesion rats. These data confirmed the existence of the projection which reached the lateral septum from the SCN and suggested to us that these synapses were so-called peptidergic synapses.

Animals↗
PubMed1981

Aging in the neuropil of cerebral cortex--a quantitative ultrastructural study.

Six age groups, each composed of four animals from each of the following ages, were used to assess age-related ultrastructural changes in the neuropil of the III layer of the frontal cortex in rats: 3, 6, 12, 18, 24 and 30 months old. Random samplings within the neuropil were taken to produce 40 electron micrographs in each rat (totaling 960). The profiles of axon terminals, dendrites and astroglial processes in the neuropil of each micrograph were traced. Then the percentage of their areas for the area of neuropil (relative volume fraction) was examined using the image analyzer system. The relative volume fractions of both the axon terminals and dendrites for the neuropil were found to have decreased in the aged rats. On the contrary, the relative volume fraction of astroglial processes for the neuropil had progressively increased with aging.

Aging↗