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Biomedical subjects

K Tamaki

Publications and source records attributed to K Tamaki.

At least 19 recordsLinked to original sources

The expression levels and the differential expression of transforming growth factor-beta receptors in dermatofibroma and dermatofibrosarcoma protuberans.

BACKGROUND: Dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP) are benign and intermediate malignant fibrotic dermal tumours, respectively. The contribution of transforming growth factor (TGF)-beta has been implicated in the progression of sclerosis in fibrotic diseases. OBJECTIVES: To investigate the expression of TGF-beta receptors in these fibrotic tumours. METHODS: We examined the expression levels of TGF-beta type I and type II receptors (TGFbeta-RI and TGFbeta-RII) in DF and DFSP using in situ hybridization and immunohistochemical analysis. We also examined the expression of TGF-beta1 and collagen type I using immunohistochemical analysis. RESULTS: We detected strong expression of TGFbeta-RI and TGFbeta-RII on epidermis and epidermal appendages, moderate expression in vascular endothelial cells, smooth muscle cells and neural tissues, and weak expression in fibroblasts in normal skin sections. The expression levels of TGFbeta-RI and TGFbeta-RII were elevated in the tissue sections of DF in comparison with normal dermal sections using in situ hybridization and immunohistochemical staining. Furthermore, the expression of TGFbeta-RI and TGFbeta-RII was strong in spindle-shaped cells around DF. The expression of TGFbeta-RI and TGFbeta-RII was decreased in DFSP in comparison with DF, and their expression was found to be homogeneous in each DFSP tumour cell. The staining for TGF-beta1 was found prominently on matrix and spindle-shaped tumour cells of DF, and peripheral regions of DFSP. Weak expression of TGF-beta1 was found on normal skin or tumour cells in the central part of DFSP. Type I collagen expression was found on spindle-shaped tumour cells in DF, but not in tumour cells of DFSP. CONCLUSIONS: These results suggest the possibility that TGF-beta signalling may contribute to the fibrosis around DF, and that TGF-beta receptors may play important roles in TGF-beta signalling. The expression patterns of TGFbeta-RI and TGFbeta-RII may be helpful in distinguishing these diseases.

Activin Receptors, Type I↗

Interleukin 12 production by monocytes from patients with psoriasis and its inhibition by ciclosporin A.

BACKGROUND: Psoriasis is a T-helper (Th)1 cytokine-mediated chronic skin disease and interleukin (IL)-12 has been shown to play a major role in the development of Th1 responses. OBJECTIVES: To elucidate the role of IL-12 in the pathogenesis of psoriasis and to study the effect of ciclosporin A (CsA) on Th1 deviation of this disease. PATIENTS/METHODS: We investigated IL-12 production by stimulated monocytes from patients with psoriasis who were treated with or without CsA. Monocytes were stimulated with interferon-gamma plus lipopolysaccharide (LPS) or Staphylococcus aureus Cowan strain I (SAC). The amount of IL-12 p70 produced by stimulated monocytes was evaluated by enzyme-linked immunosorbent assay. RESULTS: Compared with those from normal controls, LPS- but not SAC-stimulated monocytes from patients with psoriasis produced significantly higher amounts of IL-12. Interestingly, LPS-stimulated monocytes from patients with psoriasis treated with CsA produced significantly decreased amounts of IL-12 compared with those patients not treated with CsA. CONCLUSIONS: Our results suggest that IL-12 production by monocytes may have a critical role in the pathogenesis of psoriasis, and that the therapeutic effect of CsA on psoriasis may be achieved by correcting the deviation of the Th1/Th2 balance.

Adult↗

Serum levels of BAFF are increased in bullous pemphigoid but not in pemphigus vulgaris.

BACKGROUND: BAFF [B-cell activating factor belonging to the tumour necrosis factor (TNF) family] is a member of the TNF superfamily that regulates B-lymphocyte proliferation and survival. It has been demonstrated that increased levels of soluble BAFF are associated with systemic autoimmunity in patients with systemic lupus erythematosus, rheumatoid arthritis and Sjögren's syndrome, and in animal models of spontaneous autoimmune diseases. However, the significance of circulating BAFF in autoimmune bullous diseases is unknown. OBJECTIVES: To examine whether BAFF levels are elevated in the autoimmune blistering diseases pemphigus vulgaris (PV) and bullous pemphigoid (BP). METHODS: We examined sera obtained from 21 patients with PV, 39 patients with BP and 22 healthy donors. We performed enzyme-linked immunosorbent assays for soluble BAFF and each disease-specific antibody: antidesmoglein-3 antibody for PV and anti-BP180 antibody for BP. RESULTS: Significant elevations of serum BAFF levels were found in the patients with BP, but not with PV. There was apparently no significant association between the serum BAFF levels and titres of anti-BP180 antibodies in the patients with BP. However, serum BAFF levels tended to be more elevated in patients with a shorter disease duration. There was a tendency that BAFF levels increased before the anti-BP180 antibody levels increased at the onset of BP and quickly decreased in response to treatment. CONCLUSIONS: BAFF may be a useful marker for early activation of an autoimmune diathesis and may play a critical role in triggering activation of self-antigen-driven autoreactive B cells in BP.

Adult↗

Analysis of GM-CSF gene polymorphisms (3606T/C and 3928C/T) in Japanese patients with atopic dermatitis.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is thought to play an important role in the pathogenesis of atopic dermatitis. To examine whether GM-CSF single nucleotide polymorphisms (SNPs) are associated with susceptibility to atopic dermatitis, we investigated the genotype and allele frequencies of the SNPs 3606T/C and 3928C/T of the GM-CSF gene in 181 Japanese patients with atopic dermatitis and 100 controls, using a PCR restriction fragment length polymorphism method. A strong linkage disequilibrium existed between the polymorphisms 3606 and 3928, suggesting two common GM-CSF haplotypes, 3606*T-3928*C and 3606*C-3928*T. However, there was no significant difference in genotype or allele frequencies between patients with atopic dermatitis and controls for either of the two polymorphisms, thus GM-CSF SNPs do not appear to be associated with susceptibility to atopic dermatitis in Japanese patients. A large-scale study is necessary to confirm these findings.

Adolescent↗

Pseudoscleroderma associated with cancer.

In the period 1994-2002, we saw 71 patients with sclerotic skin changes; 66 were diagnosed with systemic sclerosis (SSc) while five (7%) were diagnosed with pseudoscleroderma associated with various malignancies. The mean duration of disease in these five patients was significantly shorter than that of patients with SSc. The incidence of positive antinuclear antibodies, Raynaud's phenomenon or oesophageal involvement in patients with pseudoscleroderma was significantly lower than that in patients with SSc. The distributions of skin sclerosis varied in each case. Serum basic fibroblast growth factor (bFGF) levels in the five patients with pseudoscleroderma were very elevated compared with levels in controls. Elevated expression of bFGF was detected on fibroblasts of affected skin and in one lung-cancer tissue sample obtained by excision.

Adenocarcinoma↗

Analysis of gene mutations in four cases of dermatofibrosarcoma protuberans.

Fusion of the collagen type I alpha 1 (COL1A1) gene with the platelet-derived growth factor B-chain (PDGFB) gene has been described 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. We examined the breakpoints of the COL1A1 gene using the tumour specimens from four patients with DFSP. The COL1A1-PDGFB fusion transcripts were detected from the cultured tumour cells by reverse transcriptase polymerase chain reaction. Sequence analysis revealed that the ends of exons 23, 25, 26 and 36 in the COL1A1 gene were fused with the start of exon 2 in the PDGFB. This study identified three novel COL1A1 breakpoints: exons 23, 26 and 36 of the COL1A1 gene. In one case, the tumour was composed of two areas that differed in cytological atypia, cellularity and mitotic activity, indicating the dedifferentiation of the tumour. In tumour cells from two different areas the same aberrant fusion transcripts were identified. These results suggest that the dedifferentiation of tumour cells has nothing to do with the specific breakpoints of the COL1A1 gene, but depends on other unknown factors.

Adult↗

[Surgical treatment for clinical stage II and III small cell lung cancer patients].

To evaluate a surgical resection in multidisciplinary treatment for clinical stage (c-stage) II and III small cell lung cancer (SCLC) patients, we examined the postoperative prognosis concerning in 18 patients who underwent complete surgical resection. Five-year survival rate of 8 c-stage II and 10 c-stage III patients showed 62.5% and 46.7%, respectively. Of these, 7 patients underwent preoperative induction chemotherapy resulting in down-staging to c-stage 0-I, and their survival rate at 5 years after sugery was as good as 68.6%. However, in 4 (57.1%) of 7 patients, tumor cells proved to be alive by pathological assessment of lymph nodes. As a consequence, it was suggested that surgery for c-stage II and III SCLC patients is a meaningful treatment considering their prognoses. In particular, even though the patients show a favorable response of preoperative chemotherapy, to completely eliminate remnant tumor cells, a surgical resection may be necessary.

Antineoplastic Combined Chemotherapy Protocols↗

Constitutively phosphorylated Smad3 interacts with Sp1 and p300 in scleroderma fibroblasts.

OBJECTIVE: To elucidate the role of transforming growth factor-beta (TGF-beta)/Smad signalling in the increased expression of the collagen gene in systemic sclerosis (SSc) fibroblasts. METHODS: Dermal fibroblasts from seven patients with diffuse SSc of recent onset and from seven healthy individuals were studied. The expression levels of Smad2, Smad3 and Smad4 proteins were determined by immunoblotting. Smad3 phosphorylation and the interaction of Smad3 with Sp1 or p300 were analysed using immunoprecipitation. The effects of overexpression of Smad proteins or Sp1 on the human alpha2(I) collagen gene transcription were investigated with chloramphenicol acetyltransferase (CAT) assays using the -772 COL1A2/CAT construct. RESULTS: Constitutive increased Smad3 phosphorylation was detected in SSc fibroblasts compared with normal fibroblasts. Increased interaction of Smad3 with Sp1 as well as p300 was also detected in SSc fibroblasts. The overexpression of Smad3 caused an increase of up to 5-fold in COL1A2 promoter activity in normal fibroblasts, while Smad3 caused a small increase in COL1A2 promoter activity in SSc fibroblasts. However, neither Smad2 nor Smad4 caused significant effects in COL1A2 promoter activity in normal fibroblasts or SSc fibroblasts. The overexpression of Sp1 caused further increase in COL1A2 promoter activity stimulated by TGF-beta in normal fibroblasts, but did not change COL1A2 promoter activity in the presence of TGF-beta in SSc fibroblasts. The combined overexpression of Smad3 and Sp1 significantly enhanced TGF-beta response in normal fibroblasts, but less markedly in SSc fibroblasts. CONCLUSIONS: These results suggested that SSc fibroblasts are less sensitive to exogenous TGF-beta stimulation because they are already activated by the autocrine TGF-beta loop.

Cells, Cultured↗

Clinical significance of serum levels of matrix metalloproteinase-13 in patients with systemic sclerosis.

OBJECTIVES: To investigate the clinical significance of serum matrix metalloproteinase-13 (MMP-13) levels in patients with systemic sclerosis (SSc). METHODS: Serum MMP-13 levels were determined by using a peptide substrate cleavage assay in 20 patients with diffuse cutaneous SSc (dcSSc), 20 with limited cutaneous SSc (lcSSc) and 10 normal controls. RESULTS: The serum MMP-13 levels in patients with dcSSc or lcSSc were significantly lower than those in normal controls (53.4 +/- 14.1 vs 73.2 +/- 11.5 ng/ml, P < 0.0005; 59.4 +/- 14.8 vs 73.2 +/- 11.5 ng/ml, P < 0.005, respectively), but there was no significant difference in the serum MMP-13 levels between patients with dcSSc and those with lcSSc. Disease duration prior to the diagnosis was significantly shorter in SSc patients with decreased serum MMP-13 levels than in those with normal levels (3.0 +/- 2.2 vs 8.6 +/- 7.6 yr, P < 0.0005). In addition, serum MMP-13 levels were moderately correlated with the duration of the disease (r = 0.451, P < 0.05). Though there was no significant difference in the frequencies of pulmonary fibrosis or reduced %DLco (diffusing capacity of lung for carbon monoxide), the frequency of reduced %VC (vital capacity) was significantly greater in patients with decreased serum MMP-13 levels than in those with normal levels (73 vs 24%, P < 0.05). CONCLUSIONS: Matrix metalloproteinase-13 may be involved in the fibrotic process of SSc, especially in the initiation of fibrosis. The serum MMP-13 levels may serve as a useful marker for the severity of pulmonary fibrosis in patients with SSc.

Adult↗

Unconditional security of a three state quantum key distribution protocol.

Quantum key distribution (QKD) protocols are cryptographic techniques with security based only on the laws of quantum mechanics. Two prominent QKD schemes are the Bennett-Brassard 1984 and Bennett 1992 protocols that use four and two quantum states, respectively. In 2000, Phoenix et al. proposed a new family of three-state protocols that offers advantages over the previous schemes. Until now, an error rate threshold for security of the symmetric trine spherical code QKD protocol has been shown only for the trivial intercept-resend eavesdropping strategy. In this Letter, we prove the unconditional security of the trine spherical code QKD protocol, demonstrating its security up to a bit error rate of 9.81%. We also discuss how this proof applies to a version of the trine spherical code QKD protocol where the error rate is evaluated from the number of inconclusive events.

Journal Article↗

Prevalence of atopic dermatitis in Japanese elementary schoolchildren.

BACKGROUND: Although there have been several reports on the prevalence of atopic dermatitis (AD) in Japanese schoolchildren based on questionnaires, there has been no nation-wide study of the frequency of this condition diagnosed by dermatologists in regular health check-ups of schoolchildren. OBJECTIVES: The objective of this work was to evaluate precisely the prevalence of AD in elementary schoolchildren in Japan based on regular health check-ups by dermatologists. METHODS: In 2001/2, elementary schoolchildren: first graders (age 6-7 years) and sixth graders (age 11-12 years) were examined by dermatologists in eight prefectures of Japan (Hokkaido, Iwate, Tokyo, Gifu, Osaka, Hiroshima, Kochi and Fukuoka). In each prefecture, public elementary schools were randomly selected from urban and rural districts. We planned to examine about 700 schoolchildren in each of urban first, urban sixth, rural first and rural sixth grades from the eight areas, a total of 22 400 children (700 x 4 x 8). AD was diagnosed by the dermatologists based on the Japanese Dermatological Association criteria for the disease. RESULTS: The point prevalence of AD was 11.2% overall (2664 of 23 719) ranging from 7.4% (Iwate) to 15.0% (Fukuoka) in the eight areas. Seventy-four per cent, 24%, 1.6% and 0.3% of those afflicted were in the mild, moderate, severe and very severe groups, respectively. Overall, the prevalence of first graders was slightly higher than that of sixth graders (11.8% vs. 10.5%, P < 0.01). There was no apparent difference in prevalence between urban and rural districts, or between boys and girls. CONCLUSIONS: The prevalence of AD in Japanese elementary schoolchildren was about 10%, three-quarters of those being mildly affected. This is the first nation-wide study made of Japanese elementary schoolchildren examined by dermatologists to evaluate the frequency of AD.

Child↗

Sclerosing panniculitis is associated with pulmonary hypertension in systemic sclerosis.

BACKGROUND: There have been no reports of patients with sclerosing panniculitis and systemic sclerosis (SSc). OBJECTIVES: To evaluate the incidence of sclerosing panniculitis in patients with SSc, and to investigate the clinical features of such cases. METHODS: In total, 128 patients with SSc treated at our clinic were investigated retrospectively. RESULTS: SSc patients with sclerosing panniculitis had pulmonary hypertension (PH), especially isolated PH, at a significantly higher incidence than those without. Among the SSc patients with PH, those with sclerosing panniculitis had pulmonary infarctions at a higher incidence than those without. CONCLUSIONS: Our results suggest that thrombosis caused by venous hypertension of the leg may be the main cause of PH in patients with SSc and sclerosing panniculitis. Sclerosing panniculitis may be a useful marker of PH in patients with SSc.

Adult↗

Onychomycosis caused by Fusarium proliferatum.

Fusarium infections in humans are usually opportunistic, but the fungus sometimes infects healthy persons, causing keratomycosis or onychomycosis. Onychomycosis is usually caused by F. solani or F. oxysporum. We report the first two cases of onychomycosis caused by F. proliferatum, and discuss methods of diagnosis and effective treatment. Nail samples from the two patients were examined by direct microscopy, cultured, and identified morphologically and genetically as F. proliferatum. Both patients were treated successfully with oral itraconazole, even though the minimum inhibitory concentration of itraconazole was relatively high in Patient 1. This is the first report of F. proliferatum as an agent of onychomycosis. Itraconazole may be effective in the treatment of onychomycosis caused by F. proliferatum.

Antifungal Agents↗

Rheumatoid factor isotypes in localized scleroderma.

Localized scleroderma is a connective tissue disorder that is sometimes accompanied by various immunological abnormalities. In this study, we analysed serum levels of rheumatoid factor (RF) isotypes in patients with localized scleroderma and in normal controls to determine if any of these isotypes reflect the severity of the disease. IgM RF, IgG RF and IgA RF were positive in 30%, 21%, and 7% of the patients, respectively. The levels of IgM RF were significantly higher in the patients with generalized morphea (GM), the most severe form of localized scleroderma, than those with linear scleroderma (LS) (P < 0.005) or normal controls (P < 0.0005). The levels of IgG RF were significantly higher in patients with GM than normal controls (P < 0.05). The levels of IgA RF were significantly higher in patients with GM or LS than normal controls (P < 0.001 and P < 0.01, respectively). The count of sclerotic lesions was significantly higher in patients with IgM RF than those without (P < 0.05). These results suggest that the presence of RF isotypes is one of the immunological abnormalities of localized scleroderma. IgM RF seemed to be most useful of these three factors to determine the severity of disease.

Adolescent↗

Interleukin-4 and interleukin-13 enhance CCL26 production in a human keratinocyte cell line, HaCaT cells.

Eotaxin-2/CCL24 and eotaxin-3/CCL26 are CC chemokines and their receptor, CC chemokine receptor 3 is preferentially expressed on eosinophils. It was reported that vascular endothelial cells and dermal fibroblasts produced CCL26. However, the regulation of CCL24 and CCL26 production in keratinocytes has not been well documented. We investigated the expression and production of CCL24 and CCL26 in the human keratinocyte cell line, HaCaT cells. Reverse transcription and polymerase chain reaction was performed using these cells and Enzyme-linked immunosorbent assay was carried out using supernatant of these cells. The production of CCL24 in HaCaT cells was slightly enhanced by IL-4 and that of CCL26 was strongly enhanced by IL-4 and IL-13. Furthermore, TNF-alpha generated a synergistic effect on IL-4 enhanced CCL26 production. Dexamethasone, IFN-gamma and the p38 mitogen-activated protein kinase inhibitor SB202190 inhibited IL-4 enhanced CCL26 production. IL-4 enhanced production of CCL26 was inhibited by leflunomide and JAK inhibitor 1, but not by JAK3 inhibitor, which indicates that it is mediated by JAK1-STAT6-dependent pathway. This result also strongly suggests the involvement of the type 2 IL-4 receptor in IL-4 enhanced production of CCL26. These results suggest that keratinocytes are involved in the migration of CC chemokine receptor 3 positive cells such as eosinophils in a Th2-dominant situation like atopic dermatitis.

Cell Line, Tumor↗