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Fumio Kaneko

Publications and source records attributed to Fumio Kaneko.

At least 19 recordsLinked to original sources
PubMed2006

Macrophage-derived chemokine (MDC)/CCL22 produced by monocyte derived dendritic cells reflects the disease activity in patients with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a recurrent inflammatory skin disease characterized by high serum levels of IgE and Th2-type cytokines such as IL-4, IL-5 or IL-13. Chemokines attract leukocytes in inflamed tissues. We have previously found that thymus and activation regulated chemokine (TARC)/CCL17 and macrophage-derived chemokine (MDC)/CCL22 are highly secreted in the plasma levels of AD patients. Dendritic cells (DCs) are antigen-presenting cells that are divided into two subgroups including monocyte derived DCs (MoDCs) and plasmacytoid DCs (pDCs). OBJECTIVES: The aim of the study was to elucidate CCL17 and CCL22 production by MoDCs in AD patients, psoriasis vulgaris (PsV) patients and healthy controls (HC). METHODS: MoDCs were obtained from AD patients, PsV patients or HC and were cultured. In addition, the chemokine levels were measured in the supernatants. RESULTS: We found that the CCL22 levels produced by MoDCs in AD patients to be significantly higher than those of PsV patients and HC. There was a significant correlation between the CCL22 levels produced by MoDCs and the SCORAD index. No significant difference in the CCL17 levels produced by MoDCs was detected among AD patients, PsV patients or HC. Immunosuppressive drugs such as dexamethasone (Dex), tacrolimus and cyclosporine (Cys) inhibited the CCL22 production by MoDCs in the AD patients. CONCLUSION: These data suggest that the CCL22 level produced by MoDCs thus reflects the disease activity of AD and it may also play an important role regarding the production of CCL22 in the pathogenesis of AD.

Adolescent↗
PubMed2006

Single nucleotide polymorphisms of Ficolin 2 gene in Behçet's disease.

BACKGROUND: Genetic susceptibility to Behçet's disease (BD) is well documented for HLA-B51 positivity. However, BD is not a simple hereditary disease and it is exaggerated by exogenous stimuli such as microorganisms' infections. Ficolin 2 is a lectin that binds to the surface of microbial cells and kills microbial cells through the activation of complement system. Novel single nucleotide polymorphisms (SNPs) of human Ficolin 2 gene (FCN2 gene) have been recently identified in Caucasian people. OBJECTIVE: The aim of the study was to elucidate the contribution of FCN2 gene in the pathogenesis of BD. METHODS: The frequencies of genotypes and alleles of FCN2 gene SNPs in the promoter regions (-987, -602, -557, -64, -4) and exon 8 (+6359, +6424) were examined in 83 patients with BD and 64 healthy controls by genotyping with a DNA sequencing method. RESULTS: There were no significant differences in genotype and allele frequencies of FCN2 gene SNPs between BD patients and healthy controls. No significant differences in genotype and allele frequencies of FCN2 gene SNPs were detected among different clinical subgroups in BD patients. Significant differences in allele frequencies of FCN gene SNPs at both -557 and -64 sites in the promoter regions were found between HLA-B51 positive groups and HLA-B51 negative groups of BD patients. CONCLUSION: The significant differences in allele frequencies of FCN2 gene SNPs in the promoter lesions (-557 and -64 sites) among HLA-B51 positive BD patients may reveal the possibility that ficolin may contribute to the innate immunity of BD among HLA-B51 haplotypes in BD patients.

Adult↗
PubMed2006

Role of IL-12B promoter polymorphism in Adamantiades-Behcet's disease susceptibility: An involvement of Th1 immunoreactivity against Streptococcus Sanguinis antigen.

Adamantiades-Behcet's disease (ABD) is a chronic inflammatory multisystem disorder. Although the precise etiology is unclear, high prevalence of human leukocyte antigen (HLA)-B51 predisposition and predominantly involved T-helper type 1 cells (Th1)-type proinflammatory cytokines and extrinsic Streptococcal infection suggest a substantial association with an immunogenetic basis and strengthens the hypothesis that IL-12, a potent inducer of Th-1 immune reaction, is a putative candidate in its pathogenesis. These clinicopathological findings led us to examine interleukin 12 p40 (IL-12B) promoter polymorphism, for which the 4-base pair (bp) heterozygous insertion has been shown to affect the gene transcription and subsequent protein production. We analyzed IL-12B promoter genotypes in 194 Japanese subjects (92 with ABD and 102 normal controls) by PCR-based restriction enzyme digestion. The frequency of the insertion heterozygosity was significantly higher in patients than in controls (49/92, 53.3% vs 39/102, 38.2%, respectively). Comparing these with HLA haplotype data, this trend was more significant in HLA-B51-negative patients (29/42, 69.0% vs 20/50, 40.0%; P = 0.005). As assessed by semiquantitative reverse transcription-PCR and ELISA, stimulation with Streptococcal antigens specifically increased expression of IL-12 p40 mRNA and protein, in conjunction with IL-12 p70 induction, in peripheral blood mononuclear cells from heterozygous patients. Our results provide evidence for anti-bacterial host response toward Th1-immunity mediated by IL-12 in patients with ABD, and the possible insight into the genetic susceptibility that is independent of HLA background.

Adult↗
PubMed2006

A case of sclerodermatous graft-versus-host disease following autologous peripheral blood stem cell transplantation.

We report a 65-year-old woman with chronic graft-versus-host disease (GVHD) who developed severely sclerotic skin on the fingers, hand and trunk following autologous peripheral blood stem cell transplantation (APBSCT). The patient had suffered from breast cancer and been treated with surgery and chemotherapy. She showed pancytopenia and was treated with APBCST. Four years after APBSCT, she developed the severe sclerotic changes on the fingers, hands, extremities and trunk. The skin biopsy showed a flattened epidermis and a proliferation of collagen bundles in the dermis. No anti-nucleolar DNA titers were detected in the serum. She was diagnosed with chronic GVHD. Despite treatment with oral prednisolone, the skin sclerotic change developed and the breast cancer recurred. She died due to pericarditis. This is a rare case of sclerodermatous GVHD following APBSCT. The serum interleukin (IL)-12 levels were examined during the treatment.

Aged↗
PubMed2005

Usefulness of BP180 NC16a enzyme-linked immunosorbent assay in the serodiagnosis of pemphigoid gestationis and in differentiating between pemphigoid gestationis and pruritic urticarial papules and plaques of pregnancy.

BACKGROUND: Pemphigoid gestationis (PG) is a rare pregnancy-associated subepidermal immunobullous disease that targets hemidesmosomal proteins, particularly BP180. Clinically, PG can resemble the eruption known as polymorphic urticarial papules and plaques of pregnancy (PUPPP), and accurate differentiation between these 2 pruritic pregnancy dermatoses has important implications for fetal and maternal prognoses. Results of epitope mapping studies show that IgG autoantibodies in up to 90% of PG serum samples target the well-defined membrane-proximal NC16a domain of BP180. OBJECTIVE: To examine the usefulness of a commercially available NC16a domain enzyme-linked immunosorbent assay in the serodiagnosis of PG and in the differentiation of PG from PUPPP. PARTICIPANTS: A total of 412 women consisting of pretreatment patients with PG (n = 82), patients with PUPPP (n = 164), and age- and sex-matched controls (n = 166). METHODS: All serum samples were assayed in duplicate. Receiver operating characteristic analyses were performed to determine a cutoff value for the diagnosis of PG and for differentiation from PUPPP and controls. RESULTS: A cutoff value of 10 enzyme-linked immunosorbent assay units was associated with specificity and sensitivity of 96%. CONCLUSIONS: The NC16a enzyme-linked immunosorbent assay is highly sensitive and highly specific in differentiating PG from PUPPP, and it is potentially a valuable tool in the serodiagnosis of PG.

Adult↗
PubMed2005

c-kit Mutations in patients with childhood-onset mastocytosis and genotype-phenotype correlation.

Mastocytosis represents a clonal proliferation of mast cell hematopoietic progenitors caused by gain-of-function mutations of the c-kit gene. The heterogeneity of c-kit mutations may have contributed to difficulties in characterizing genotype-phenotype correlation of the disease. Our goal was to analyze a set of reported pathogenic c-kit mutations in patients with childhood-onset cutaneous mastocytosis, in comparison with those with adult-onset disease, and to correlate these with clinical presentation. We performed polymerase chain reaction and direct sequencing using genomic DNA samples from 16 nonfamilial Japanese patients with indolent cutaneous mastocytosis (12 with childhood-onset disease and 4 with adult-onset disease) to look for the most common c-kit mutations at codons 816, 560, 820, and 839. A substantial number of patients had missense codon 816 mutations (10 of 12 in the childhood-onset group, 83.3%; and 4 of 4 in the adult-onset group, 100%). The most common mutation was Asp816Val (9 of 16, 64.3%) followed by Asp816Phe (5 of 16, 35.7%). Moreover, children with the Asp816Phe mutation developed cutaneous mastocytosis at an earlier age as compared to those with the Asp816Val mutation (mean age of onset, 1.3 months versus 5.9 months, respectively; P = 0.068). No other mutation variations were found in our cohort. In summary, we confirmed a high incidence of two distinct c-kit mutations, Asp816Val and Asp816Phe, in patients with childhood-onset cutaneous mastocytosis. Our results provide new insights into common c-kit mutations, which may contribute to different clinical courses of the disease.

Adolescent↗
PubMed2005

Pericostal tuberculosis diagnosed by fine needle aspiration biopsy: report of a case with a review of the literature.

We present an 81-year-old woman with pericostal tuberculosis, a rare disease recently, without a past history of pulmonary tuberculosis or tuberculous pleurisy. She developed a subcutaneous nodule on her right chest. She was suspected of skin tuberculosis after the confirmation of acid-fast bacilli in a fine needle aspiration material of the nodule. A tuberculin skin test was strongly positive. The nodule was resected, and preclusive antituberculosis chemotherapy with rifampicin and isoniazid was started. The histological findings included granulomatous changes, central necrosis and Langhans' giant cells. Mycobacterium tuberculosis was identified from a culture of the specimen. About six months after the operation, no erythema, nodule or abscess was observed. We first suspected that she had mammary carcinoma and therefore observed the nodules on the thorax; it is important to differentiate tuberculosis from neoplasms. We also reviewed 22 cases of pericostal tuberculosis in Japan reported in the 15 years from 1976 to 2002.

Aged↗
PubMed2004

Enhanced TARC production by dust-mite allergens and its modulation by immunosuppressive drugs in PBMCs from patients with atopic dermatitis.

BACKGROUND: Thymus and activation regulated chemokine (TARC) is a CC chemokine that attracts CCR4+ T cells. We reported previously that TARC is an important chemokine that defines Th2 imbalance in the pathogenesis of atopic dermatitis (AD). OBJECTIVES: This study was undertaken to clarify TARC producing cells in peripheral blood mononuclear cells (PBMCs), the regulation of dust mite-allergen clude extract (DME) and different immunosuppressive drugs (Tacrolimus (FK506), cyclosporine (CsA), dexamethasone (Dex)) on TARC production by peripheral PBMCs from AD patients in vitro. METHODS: Monocyte derived dendritic cells (MoDCs) were generated from and TARC mRNA levels were examined and comapared with those from T cells in PBMCs from AD patients. PBMCs were cultured with or without DME and/or immunosuppressive drugs (Tacrolimus, CsA, Dex) for 7 days and TARC levels were measured. RESULTS: PBMCs from AD patients which were cultured with DME stimulation for 7 days showed significantly higher levels of TARC production than those from healthy controls. RT-PCR demonstrated that TARC mRNA was expressed in CD4+ T cells, CD8+ T cells and MoDCs. Tacrolimus, CsA and Dex individually suppressed TARC production by PBMCs from AD patients which were co-cultured with DME for 7 days. Gel shift analysis revealed differential inhibitory effects of these immunosuppressive drugs on NFkappaB activity in PBMCs from AD patients. CONCLUSION: Our data demonstrate that TARC producing cells are MoDCs, T cells as well as epidermal keratinocytes in AD. We suggest that MoDCs might regulate the immune responses by attracting T cells and CD25+ T cells in the pathogenesis of AD. We also showed the important role of DME on TARC production and the inhibitory effect of the immunosuppressive drugs on TARC production by PBMCs from AD patients, that can regulate ongoing immune responses in the pathogenesis of AD.

Adult↗
PubMed2004

Effect of an antiallergic drug (Olopatadine hydrochloride) on TARC/CCL17 and MDC/CCL22 production by PBMCs from patients with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by the predominant infiltration of Th2-type cells in lesional skin. Thymus and activation-regulated chemokine (TARC/CCL17) and monocyte-derived chemokine (MDC/CCL22) are Th2-type cytokines, and it has been reported that serum CCL17 and CCL22 levels are associated with AD disease activity. Olopatadine hydrochloride (Olopatadine) is an antiallergic drug with selective histamine H(1) receptor antagonist activity. The effect of Olopatadine on chemokine production by peripheral blood mononuclear cells (PBMCs) in AD patients has not been completely elucidated. OBJECTIVES: This study was undertaken to clarify the effects of Olopatadine on CCL17 and CCL22 production by PBMCs from patients with AD during the treatment. METHODS: We measured plasma levels of CCL17, CCL22, IFNgamma, IL-12 and IL-18 in 15 patients with AD before and after treatment with oral Olopatadine (10 mg/day) for 4 weeks. We also examined disease activity using SCORAD index, eosinophil numbers in peripheral blood and serum levels of LDH. PBMCs from the patients were taken before and after the treatment and cultured with or without dust mite allergen extract (DME) for 3 or 5 days. CCL17, CCL22, IFNgamma, IL-12 and IL-18 levels in the supernatants of cultured PBMCs were measured. RESULTS: SCORAD index and eosinophil numbers in peripheral blood significantly decreased during treatment of AD patients with oral Olopatadine and topical corticosteroids for 4 weeks. The plasma levels of CCL17 and CCL22 significantly decreased after the treatment compared with before the treatment (p<0.05) and were significantly correlated with SCORAD index. PBMCs from AD patients taken after the treatment and cultured with DME for 5 days, showed significantly lower levels of CCL17 production than those taken before the treatment (p=0.018). PBMCs from AD patients taken after the treatment and cultured with DME for 5 days, also showed significantly lower levels of IFNgamma production than those taken before the treatment (p=0.012). CONCLUSION: Our data demonstrate that Olopatadine inhibits CCL17 and CCL22 production by PBMCs from AD patients, which are important regulators of Th2 recruitment in the skin.

Adult↗
PubMed2004

CpG immunostimulatory sequences enhance contact hypersensitivity responses in mice.

Bacterial DNA and synthetic cytidine-phosphate-guanosine-oligodeoxynucleotides (CpG ODN) potently activate dendritic cells (DC) and therefore have been proposed as adjuvants for vaccination strategies. Although CpG ODN are considered as safe adjuvants this study shows that CpG ODN are responsible for enhanced antigen-specific skin inflammatory reactions. We used the murine model of contact hypersensitivity (CHS) to 2,4-dinitrofluorobenzene (DNFB) in which hapten-specific CD8+T cytotoxic 1 cells are effector cells. Subcutaneous injection of CpG ODN, 1 d before sensitization enhanced the CHS response to DNFB and resulted in increased recruitment of CD8+ T cells at the challenge sites, whereas control ODN injection did not have any effect. This effect was local and not systemic as it was only observed when DNFB was applied at the same site as the CpG motifs. CpG ODN-induced enhancement of CHS was due to increased antigen-presenting cell functions of DC since: (i) CpG ODN-injected skin revealed upregulated expression of major histocompatibility complex class II, CD80, and CD86 molecules and (ii) CpG ODN treatment of DNFB-derivatized DC enhanced the intensity of CHS responses after in vivo transfer. Taken together, the results show that CpG ODN may be responsible for immune side-effects such as worsening of T cell-mediated skin diseases.

Adjuvants, Immunologic↗
PubMed2004

A case of generalized pustular psoriasis associated with Turner syndrome.

UNLABELLED: We report a 27-year-old Japanese woman with Turner syndrome who had generalized pustular psoriasis of the von Zumbusch type. She developed a febrile diffuse erythema and pustular eruption without any history of preceding psoriasis vulgaris or drug ingestion. Oral treatment with 3.2 mg/kg cyclosporin per day successfully resulted in rapid improvement, followed by a complete remission. To our knowledge, this is the first report describing the unusual coexistence of these two systemic disorders. We discuss a hormone imbalance that might have contributed to the predisposition to pustular psoriasis and difficulties in the management of the patent's treatment. ABBREVIATIONS: TS: Turner syndrome, GPP: generalized pustular psoriasis

Adult↗
PubMed2004

A case of anti-p200 pemphigoid with autoantibodies against both a novel 200-kD dermal antigen and the 290-kD epidermolysis bullosa acquisita antigen.

BACKGROUND: Anti-p200 pemphigoid with autoantibodies against the 200-kD dermal antigen has recently been identified. OBJECTIVES: Our patient showed small and tense blisters on her face and trunk. METHODS: Immunoblotting (IB), using extracts of normal human epidermis and dermal skin, and immunoelectron microscopy (IEM), using normal human skin, were performed using the patient's serum. RESULTS: IB analysis showed that the patient's serum did not react with 180-kD bullous pemphigoid (BP180) or BP230 antigens; however, IgG autoantibodies in the patient's serum reacted with a 200-kD dermal antigen as well as the 290-kD epidermolysis bullosa acquisita (EBA) antigen. IEM showed that IgG antibodies in the patient's serum bound to the lamina lucida, as well as both the lamina densa and sublamina densa. After the treatment with prednisolone, the 290-kD protein reactivity decreased rapidly; however, the 200-kD protein band was still observed. CONCLUSION: We describe a rare case with immunoreactive autoantibodies against both a novel dermal 200-kD autoantigen and the 290-kD EBA antigen.

Adult↗
PubMed2004

Development of antigen-specific ELISA for circulating autoantibodies to extracellular matrix protein 1 in lichen sclerosus.

Lichen sclerosus is a common, acquired chronic inflammatory skin disease of unknown etiology, although circulating autoantibodies to the glycoprotein extracellular matrix protein 1 (ECM1) have been detected in most patients' sera. We have examined the nature of ECM1 epitopes in lichen sclerosus sera, developed an ELISA system for serologic diagnosis, and assessed clinicopathological correlation between ELISA titer and disease. Epitope-mapping studies revealed that lichen sclerosus sera most frequently recognized the distal second tandem repeat domain and carboxyl-terminus of ECM1. We analyzed serum autoantibody reactivity against this immunodominant epitope in 413 individuals (95 subjects with lichen sclerosus, 161 normal control subjects, and 157 subjects with other autoimmune basement membrane or sclerosing diseases). The ELISA assay was highly sensitive; 76 of 95 lichen sclerosus patients (80.0%) exhibited IgG reactivity. It was also highly specific (93.7%) in discriminating between lichen sclerosus and other disease/control sera. Higher anti-ECM1 titers also correlated with more longstanding and refractory disease and cases complicated by squamous cell carcinoma. Furthermore, passive transfer of affinity-purified patient IgG reproduced some histologic and immunopathologic features of lichen sclerosus skin. This new ELISA is valuable for the accurate detection and quantification of anti-ECM1 autoantibodies. Moreover, the values may have clinical significance in patients with lichen sclerosus.

Animals↗