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Biomedical subjects

Yuichiro Tsunemi

Publications and source records attributed to Yuichiro Tsunemi.

At least 37 records · Page 2Linked to original sources

Variations in the human Th2-specific chemokine TARC gene.

Th2-specific chemokine thymus and activation-regulated chemokine (TARC)/CC chemokine ligand (CCL)17 is highly implicated in the pathogenesis of Th-2-dominated allergic diseases such as bronchial asthma (BA) and atopic dermatitis (AD). We performed polymorphism screening of the coding and promoter regions of the TARC gene. We found two rare variations in the coding region of exon 3 (2134C>T and 2037G>A) and a single nucleotide polymorphism (SNP) in the 5'-flanking region (-431C>T). Individuals carrying the 431T allele showed significantly increased serum levels of TARC compared with those not carrying the 431T allele, suggesting that this SNP has functional significance. However, when the genotypes at the SNP site were determined for 158 healthy individuals, 105 patients with BA and 148 patients with AD, we observed no significant association of the SNP with susceptibility to BA or AD.

Asthma↗

Dermal endothelial cells express eotaxin in hypereosinophilic syndrome.

We describe a patient with hypereosinophilic syndrome, who had severe cutaneous eruptions. Immunohistochemical study revealed that dermal endothelial cells in the lesional skin of this patient expressed eotaxin, which indicates eotaxin plays a part in inducing eosinophil migration into cutaneous tissue in hypereosinophilic syndrome.

Aged↗

Analysis of gene mutations in three cases of dermatofibrosarcoma protuberans (DFSP): ordinary DFSP, DFSP with fibrosarcomatous lesion (DFSP-FS) and lung metastasis of DFSP-FS.

BACKGROUND: Fusion of the collagen type I alpha 1 (COL1A1) gene with the platelet-derived growth factor B-chain (PDGFB) gene has been pointed out in dermatofibrosarcoma protuberans (DFSP). Various exons of the COL1A1 gene have been shown to be involved in the fusion with exon 2 of the PDGFB gene. OBJECTIVE: We studied the breakpoints of the COL1A1 gene using the tumor specimens from three patients with DFSP. METHODS: Reverse transcriptase-polymerase chain reaction (PCR) was performed using cultured DFSP tumor cells or frozen tissue. Nucleotide sequence analysis was carried out using the PCR products to identify the breakpoints. RESULTS: Cases 1, 2 and 3 were diagnosed as ordinary DFSP, DFSP with fibrosarcomatous lesion (DFSP-FS) and lung metastasis of DFSP-FS, respectively. The COL1A1-PDGFB fusion transcripts were detected from the tumor specimens. Sequence analysis revealed that the ends of exons 42, 29 and 38 in the COL1A1 gene were fused with the start of exon 2 in the PDGFB gene in case 1, 2 and 3, respectively. CONCLUSION: This study identified a novel COL1A1 breakpoint, namely, exon 42 of the COL1A1 gene. Detection of the aberrant fusion transcript seems to be useful at differential diagnosis both in primary and metastatic lesions.

Adolescent↗

Increased serum cutaneous T cell-attracting chemokine (CCL27) levels in patients with atopic dermatitis and psoriasis vulgaris.

BACKGROUND: Both atopic dermatitis (AD) and psoriasis vulgaris (PsV) are characterized as chronic and relapsing inflammatory skin diseases associated with various immunologic abnormalities. Cutaneous T cell-attracting chemokine (CTACK; CCL27) is a member of the CC chemokine family and a functional ligand for CC chemokine receptor 10. It is selectively expressed in skin and attracts CC chemokine receptor 10-expressing skin-homing memory T cells. The epidermal keratinocyte is a main source of CTACK, suggesting the involvement of various inflammatory skin diseases. OBJECTIVE: The purpose of this investigation was to clarify whether CTACK produced by keratinocytes is detected in the sera of patients with AD and PsV and to examine the correlation between the serum CTACK levels and disease activity of patients with AD and PsV. METHODS: We measured the serum CTACK levels in 50 patients with AD, 30 patients with PsV, and 22 healthy control subjects. We also divided 50 patients with AD into 3 groups (ie, those with mild, moderate, and severe disease) and compared them among 3 categories. Moreover, we compared the serum CTACK levels of patients with AD and PsV with clinical or laboratory data. Immunohistochemical staining of CTACK and IFN-induced protein of 10 kd (IP-10; CXCL10) was performed on the lesional skin of patients with AD and PsV. RESULTS: The serum CTACK levels in patients with AD and PsV were significantly higher than those in healthy control subjects. The serum CTACK levels in patients with AD significantly correlated with scoring atopic dermatitis (SCORAD) scores, serum soluble IL-2 receptor levels, serum soluble E-selectin levels, serum thymus and activation-regulated chemokine levels, and serum macrophage-derived chemokine levels. Serum CTACK levels in patients with PsV significantly correlated with the serum IP-10 levels but not with the Psoriasis Area and Severity Index score. Immunohistochemical staining showed CTACK was strongly expressed in lesional ke-ratinocytes of patients with AD and PsV, whereas IP-10 was strongly expressed in lesional keratinocytes of patients with PsV and focally in those with AD. CONCLUSION: These results suggest that CTACK might be one of the important chemokines for the pathogenesis of AD and PsV.

Adult↗

Multiple eruptive dermatofibromas with CD34+ cells in a patient with hypertriglyceridemia.

Multiple eruptive dermatofibromas (MEDF) are rare and have been thought to be associated with altered immunity. It has been reported that dermatofibromas (DFs) are positive for factor X IIIa but not for CD34. In this report, we describe a 34-year-old Japanese woman with MEDF and persistent hypertriglyceridemia. Histopathological examination revealed that several areas in larger nodules, showing higher cellularity and storiform growth pattern, had CD34+ cells. Our case and the review of previous reports suggest that hyperlipidemia, including hypertriglyceridemia, could induce MEDF and that highly cellular areas in DFs are sometimes positive for CD34.

Adult↗

Lack of association between the promoter polymorphisms at positions -308 and -238 of the tumor necrosis factor alpha gene and psoriasis vulgaris in Japanese patients.

BACKGROUND: Psoriasis features an increased level and activity of tumor necrosis factor alpha (TNF-alpha). The TNF-alpha gene has single nucleotide polymorphisms (SNPs) at positions -308 (-308G>A) and -238 (-238G>A) in the promoter region, and the -238G>A SNP has been reported to be associated with psoriasis vulgaris (PV) and psoriatic arthritis in Caucasians. OBJECTIVE: To examine whether these SNPs are associated with susceptibility to PV in Japanese patients, we investigated the genotype and allele frequencies at each SNP in Japanese PV patients and in controls. METHODS: We examined 163 PV patients and 96 healthy individuals. Genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: No significant association between the genotypes or alleles of these SNPs and susceptibility to PV was observed. CONCLUSION: These SNPs themselves are not associated with susceptibility to PV in the Japanese.

Gene Frequency↗

Eotaxin gene single nucleotide polymorphisms in the promoter and exon regions are not associated with susceptibility to atopic dermatitis, but two of them in the promoter region are associated with serum IgE levels in patients with atopic dermatitis.

Eotaxin is believed to play an important role in atopic dermatitis (AD) as a potent chemoattractant and activator of eosinophils and Th2 lymphocytes. The eotaxin gene is located at chromosome 17q21.1-q21.2, and linkage findings of AD on chromosome 17 were reported. Recently we have identified single nucleotide polymorphisms (SNPs) of eotaxin gene (-426C > T, -384A > G, 67G > A). To learn whether eotaxin gene SNPs are associated with susceptibility to AD or phenotypes of AD, we investigated the genotype frequencies at each SNP of the gene in AD patients and in controls. We examined 140 Japanese AD patients and 140 healthy Japanese individuals. Genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism method. No significant difference was observed in allele or genotype frequencies of any SNP between AD patients and controls. Serum immunoglobulin E (IgE) levels were significantly lower in CT and TT genotype than in CC (P = 0.038) in -426C > T SNP, and lower in GG than in AA and AG with borderline significance (P = 0.053) in -384A > G SNP in AD patients. Eotaxin gene SNPs in the promoter and exon regions are not associated with susceptibility to AD, but two of them in the promoter region are associated with phenotype of AD.

Adolescent↗

Interleukin-13 gene polymorphism G4257A is associated with atopic dermatitis in Japanese patients.

Interleukin (IL)-13 plays an important role in the induction of immunoglobulin E (IgE) and in the pathogenesis of atopic dermatitis (AD). We investigated the allele and genotype frequencies of three IL-13 single nucleotide polymorphisms (SNPs) (A704C and C1103T in the promoter region and G4257A in exon 4) in Japanese patients with AD. For A704C and C1103T SNPs, there were no significant differences in allele or genotype frequencies between AD patients and controls. For G4257A SNP, A allele was significantly increased in AD patients (39.5%) compared with controls (29.4%) (P = 0.016). The same proportion of each genotype and allele was observed in the patient subgroup with and without asthma. Serum IgE levels and peripheral eosinophil counts were not significantly different among genotypes in G4257A SNP. There was also no significant difference in allele or genotype frequencies between AD patients with mild disease and those with severe disease, between those with family history of AD and those without it, or between those with family history of atopic disorders and those without it. This result suggests that 4257A allele is associated with susceptibility to AD and that it may function in the pathogenesis of AD itself, presumably by other mechanisms than inducing IgE production.

Adolescent↗

Interleukin-12 p40 gene (IL12B) 3'-untranslated region polymorphism is associated with susceptibility to atopic dermatitis and psoriasis vulgaris.

Interleukin-12 (IL-12) is believed to play an important role in inducing Th1-type cytokine profiles. Atopic dermatitis (AD) and psoriasis vulgaris (PsV) are considered to be Th2 and Th1 type disease, respectively. The IL-12 p40 subunit gene (IL12B) is located at chromosome 5q31-33 and linkage findings of AD on 5q31 were reported. Recently single nucleotide polymorphism (SNP) (1188A/C) of IL12B has been reported. In function, it has been reported that this SNP is associated with IL12B mRNA expression levels. To learn whether this SNP is associated with susceptibility to AD or PsV, we investigated the genotype and allele frequencies of the SNP in AD patients, in PsV patients and in controls, examining 164 AD patients, 143 PsV patients and 100 healthy individuals in Japanese population. Genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism method. The A allele was decreased in AD patients (40.9%, p = 0.031) and increased in PsV patients (60.1%, p = 0.035) compared with controls (50.5%). This suggests that IL12B SNP is associated with susceptibility to AD and PsV, presumably by affecting the Th1/Th2 balance.

3' Untranslated Regions↗

Polymorphisms of vitamin D receptor gene in Japanese patients with psoriasis vulgaris.

We examined polymorphisms of vitamin D receptor (VDR) gene in Japanese patients with psoriasis vulgaris (PsV). We also studied the association between VDR gene polymorphisms and the response to vitamin D (VD) topical treatment in psoriatic patients. FokI, BsmI, ApaI and TaqI genotypes were determined by restriction fragment patterns in patients (n = 115) and controls (n = 69). In addition, 54 psoriatic patients were divided into two groups in terms of their response to VD (tacalcitol) topical treatment: non-responsive (n = 30) and responsive (n = 24) patients. The frequencies of B allele and t allele were lower in patients than in controls (9 vs. 19%: p < 0.01, 7 vs. 14%: p < 0.05, respectively). In regard to response to VD treatment, F allele was lower in non-responsive patients than in controls (47 vs. 64%, p < 0.05). We show that polymorphisms of VDR gene are associated with Japanese patients with PsV. Allelic variance in the VDR gene or other genes in linkage disequilibrium with this gene might predispose to the development of PsV.

Adult↗