Biomedical subjects

Kunihiro Nishimura

Publications and source records attributed to Kunihiro Nishimura.

8 recordsLinked to original sources

PubMed2023

Association of thyroid peroxidase antibody with the RNF213 p.R4810K variant in ischemic stroke/transient ischemic attack.

BACKGROUND AND AIMS: RNF213 is a susceptibility gene for moyamoya disease and vasospastic angina, with a second hit considered necessary for their development. Elevated thyroid peroxidase antibody (TPO-Ab) levels have been observed in both diseases, suggesting a possible role of TPO-Ab as a second hit for developing RNF213-related vasculopathy. We investigated the association of TPO-Ab levels with RNF213-related ischemic stroke (IS)/transient ischemic attack (TIA), other than moyamoya disease. METHODS: From the National Cerebral and Cardiovascular Center Genome Registry, a multicenter, prospective, observational study, we enrolled patients with IS/TIA who were admitted within 1 week of onset. Patients with IS/TIA due to definite moyamoya disease or hemorrhagic stroke were excluded. Participants underwent genotyping for RNF213 p. R4810K, and baseline characteristics and TPO-Ab levels were compared between RNF213 p. R4810K variant carriers and non-carriers. RESULTS: In total, 2090 IS/TIA patients were analyzed [733 women (35.1%); median age 74 (interquartile range, 63-81) years, baseline NIHSS score 3 (2-6)], and 85 (4.1%) of them carried the variant. Median TPO-Ab levels were significantly higher in variant carriers (8.5 IU/mL vs. 2.1 IU/mL, p < 0.01), who also showed a higher frequency of elevated TPO-Ab levels (>16 IU/mL) (27.1% vs. 4.4%). In the multivariate analysis, presence of the RNF213 p. R4810K variant (adjusted odds ratio, 12.42; 95% confidential interval, 6.23-24.75) was significantly associated with elevated TPO-Ab levels. CONCLUSIONS: Elevated TPO-Ab levels may be significantly associated with presence of the RNF213 p. R4810K variant in IS/TIA patients. Thus, TPO-Ab may inherently modify IS/TIA development in RNF213 p. R4810K variant carriers.

Humans↗

PubMed2006

Global variation in copy number in the human genome.

Copy number variation (CNV) of DNA sequences is functionally significant but has yet to be fully ascertained. We have constructed a first-generation CNV map of the human genome through the study of 270 individuals from four populations with ancestry in Europe, Africa or Asia (the HapMap collection). DNA from these individuals was screened for CNV using two complementary technologies: single-nucleotide polymorphism (SNP) genotyping arrays, and clone-based comparative genomic hybridization. A total of 1,447 copy number variable regions (CNVRs), which can encompass overlapping or adjacent gains or losses, covering 360 megabases (12% of the genome) were identified in these populations. These CNVRs contained hundreds of genes, disease loci, functional elements and segmental duplications. Notably, the CNVRs encompassed more nucleotide content per genome than SNPs, underscoring the importance of CNV in genetic diversity and evolution. The data obtained delineate linkage disequilibrium patterns for many CNVs, and reveal marked variation in copy number among populations. We also demonstrate the utility of this resource for genetic disease studies.

Chromosome Mapping↗

PubMed2006

Noise reduction from genotyping microarrays using probe level information.

Genomic copy number change is one of the important phenomenon observed in cancer and other genetic disorders. Recently oligonucleotide microarrays have been used to analyze changes in the copy number. Although high density microarrays provide genome wide useful data on copy number, they are often associated with substantial amount of experimental noise that could affect the performance of the analyses. We used the high density oligonucleotide genotyping microarrays in our experiments that uses redundant probe tiling approach for individual SNPs. We found that the noise in the genotyping microarray data is associated with several experimental steps during target preparation and devised an algorithm that takes into account those experimental parameters. Additionally, defective probes that do not hybridize well to the target and therefore could not be modified inherently were detected and omitted automatically by using the algorithm. When we applied the algorithm to actual datasets, we could reduce the noise substantially without compressing the dynamic range. Additionally, combinatorial use of our noise reduction algorithm and conventional breakpoint detection algorithm successfully detected a microamplification of c-myc which was overlooked in the raw data. The algorithm described here is freely available with the software upon request to all non-profit researchers.

Adenocarcinoma↗

PubMed2005

Allelic dosage analysis with genotyping microarrays.

Genomic alternations, including dosage and allelic imbalance, constitute a major basis of neoplastic and other genetic disorders. Using oligonucleotide genotyping microarrays, here we report the development and usage of an algorithm, called genome imbalance map (GIM) algorithm, for allelic as well as total gene dosage analysis. Using the GIM algorithm, global genome imbalance status at over 100,000 loci was simultaneously analyzed with unprecedented accuracy and allelic discrimination.

Algorithms↗

PubMed2004

Distinct chromosomal bias of gene expression signatures in the progression of hepatocellular carcinoma.

To identify the chromosomal aberrations associated with the progression of liver cancer, we applied expression imbalance map analysis to gene expression data from 31 hepatocellular carcinomas and 19 noncancerous tissues. Expression imbalance map analysis, which detects mRNA expression imbalance correlated with chromosomal regions, showed that expression gains of 1q21-23 (74%), 8q13-21 (48%), 12q23-24 (41%), 17q12-21(48%), 17q25 (25%), and 20q11 (22%) and losses of 4q13 (48%), 8p12-21 (32%), 13q14 (32%), and 17p13 (29%) were significantly associated with hepatocellular carcinoma. Most regions with altered expression identified by expression imbalance map were also identified in previous reports using comparative genomic hybridization. We demonstrated chromosomal copy number gain in 1q21-23 and loss in 17p13 by genomic quantitative PCR, suggesting that gene expression profiles reflect chromosomal alterations. Furthermore, expression imbalance map analysis revealed that more poorly differentiated hepatocellular carcinoma contain more chromosomal alterations, which are accumulated in a stepwise manner in the course of hepatocellular carcinoma progression: expression imbalance of 1q, 8p, 8q, and 17p occur as early events in hepatocarcinogenesis, and 12q, 17q25 and 20q occur as later events. In particular, expression gain of 17q12-21 and loss of 4q were seen to accumulate constantly through the dedifferentiation process. Our data suggest that gene expression profiles are subject to chromosomal bias and that expression imbalance map can correlate gene expression to gene loci with high resolution and sensitivity.

Aged↗

PubMed2004

[Topics on immunological tests for rheumatoid arthritis].

To prevent joint destruction, it is important to diagnose RA early and to speculate the prognosis. Several new laboratory tests have been developed for this purpose. In addition to rheumatoid factor (RF), IgG-RF, anti-agalactosyl IgG antibodies (CARF), and matrix metalloproteinase 3 (MMP-3) have become available as diagnostic tests for RA. Among them, anti-cyclic citrullinated peptide antibodies (anti-CCP antibodies) have the sensitivity and specificity of 81.0% and 92.4%, respectively, which are superior to other laboratory tests by ROC analysis. Moreover, the specificity of anti-CCP antibodies to diagnose early RA was much higher than that of RF, although the sensitivity of CARF was slightly high compared with that of RF. In contrast, MMP-3 is thought to be an evaluative test for the activity of RA because a significant correlation was found between MMP-3 and CRP, but MMP-3 has a possibility as a prognostic test to know the joint damage of RA. We have shown that the progression of joint damage (Sharp score) was faster in MMP-3-positive patients than negative patients. Anti-CCP antibodies was also reported to associate with the progression of joint damage and may be used also as a prognostic test. We next examined how efficiently was the diagnosis of RA made by combining these laboratory tests. Although anti-CCP antibodies are highly specific to RA, the specificity of RF was not so high but became up to 92% when combined with MMP-3. In order to diagnose RA efficiently, we may firstly examine RF, next MMP-3 if RF is positive, and anti-CCP antibodies if RF is negative.

Arthritis, Rheumatoid↗

PubMed2003

Two distinct gene expression signatures in pediatric acute lymphoblastic leukemia with MLL rearrangements.

Acute lymphoblastic leukemia (ALL) with 11q23 translocations is usually associated with MLL gene rearrangement, but little is known about its leukemogenesis. We analyzed the gene expression profiles of pediatric ALL samples according to their translocations. Using oligonucleotide microarray analysis, we identified distinct expression profiles for 23 ALL samples with 11q23 translocations, including t(4;11) (n = 15), t(11;19) (n = 6), and t(5;11) (n = 2), compared with 9 ALL samples with other translocations, including t(12;21) (n = 6) and t(1;19) (n = 3). Gene expression scores of FLT3, MeisI, and CD44 for samples with MLL rearrangements were particularly high compared with those for other ALL samples. Statistical analysis of the gene expression profiles for the 21 ALL samples with MLL rearrangements at diagnosis revealed two subgroups that exclusively correlated with prognosis but not with any other clinico-pathological factor. The transcription factors CBF2 and CDP were highly expressed in the poor and good prognosis subgroups, respectively. In addition, their downstream target genes were differentially expressed. These findings provide new insights into the biological mechanisms of leukemogenesis and prognosis for pediatric ALL with MLL rearrangements.

Child↗

PubMed2003

Expression imbalance map: a new visualization method for detection of mRNA expression imbalance regions.

We describe the development of a new visualization method, called the expression imbalance map (EIM), for detecting mRNA expression imbalance regions, reflecting genomic losses and gains at a much higher resolution than conventional technologies such as comparative genomic hybridization (CGH). Simple spatial mapping of the microarray expression profiles on chromosomal location provides little information about genomic structure, because mRNA expression levels do not completely reflect genomic copy number and some microarray probes would be of low quality. The EIM, which does not employ arbitrary selection of thresholds in conjunction with hypergeometric distribution-based algorithm, has a high tolerance of these complex factors. The EIM could detect regionally underexpressed or overexpressed genes (called, here, an expression imbalance region) in lung cancer specimens from their gene expression data of oligonucleotide microarray. Many known as well as potential loci with frequent genomic losses or gains were detected as expression imbalance regions by the EIM. Therefore, the EIM should provide the user with further insight into genomic structure through mRNA expression.

Allelic Imbalance↗