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Masutaka Furue

Publications and source records attributed to Masutaka Furue.

At least 37 records · Page 2Linked to original sources
PubMed2005

beta-Catenin mutation and its nuclear localization are confirmed to be frequent causes of Wnt signaling pathway activation in pilomatricomas.

BACKGROUND: beta-Catenin has been shown to play an important role in the formation of hair follicle-related tumors, including pilomatricomas. Several investigators have shown that beta-catenin gene mutation is observed in pilomatricomas. However, the relationship between the pattern of beta-catenin localization in the cell and beta-catenin gene mutation is still controversial. OBJECTIVES: This work was performed to determine the frequency of beta-catenin nuclear localization in pilomatricoma, the relationship between the pattern of beta-catenin localization and beta-catenin mutation, and the involvement of APC mutation. METHODS: Typical 32 pilomatricomas were examined for beta-catenin expression by immunostaining. Genomic DNA was extracted, amplified and sequenced from 23 pilomaticomas with nuclear beta-catenin staining and 4 pilomaticomas without nuclear beta-catenin staining. Mutations of beta-catenin gene were confirmed by subcloning assay and restriction endonuclease assay. RESULTS: Using immunostaining, we found that 81% (26/32) of pilomatricomas displayed nuclear beta-catenin staining in basophilic cells. Sequence analysis revealed that 61% (14/23) contained mutations in exon 3 of beta-catenin. However, no mutations were detected in 4 pilomaticomas without beta-catenin nuclear staining. Detected mutations were adjacent to or abolished well-known regulatory phosphorylation sites of beta-catenin. APC gene mutations were not detected in 27 pilomatricomas with/without beta-catenin nuclear staining. CONCLUSIONS: These results confirmed that beta-catenin mutation and its nuclear localization are frequent causes of Wnt signaling pathway activation and suggested that beta-catenin activation mutations contribute to tumorigenesis of pilomatricomas.

Adult↗
PubMed2005

Differential role of MAPK signaling in human dendritic cell maturation and Th1/Th2 engagement.

Dendritic cells (DCs) are potent antigen-presenting cells that can stimulate resting T cells in the primary immune response. During the maturation process, immature DCs lose their ability to internalize antigens and they acquire the capacity to present antigens to naive T cells. Many observations have suggested that distinct DC subsets might differentially regulate Th responses. However, recent reports suggest that specific subsets of either murine or human DCs cultured in vitro with different stimuli respond with great plasticity in terms of both gene expression and cytokine secretion. Thus, the microenvironment of DCs may determine the nature of mature DCs and the subsequent immune response. The mechanism by which the character of DCs is determined is unknown. The in vitro maturation process of human monocyte-derived DCs (MoDC) can be initiated by various stimuli. Many stimuli induce phosphorylation of extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinases (JNK), and p38 MAPK in DCs during maturation. Such kinase-specific inhibitors help to reveal the functions of MAPKs in the maturation of human MoDCs. Recent studies suggest that three MAPK signaling pathways differentially regulate all aspects of phenotypic maturation, cytokine production, and functional maturation of MoDCs. Thus, distinct maturation of DCs may be induced by modulating the balance of phosphorylation of the three MAPKs. In this review, we summarize the role of MAPK signaling pathways in the maturation of human MoDCs.

Cell Differentiation↗
PubMed2005

Molecular analysis of a novel hereditary C3 deficiency with systemic lupus erythematosus.

A case of inherited homozygous complement C3 deficiency (C3D) in a patient with systemic lupus erythematosus (SLE) and the molecular basis for this deficiency are reported. A 22-year-old Japanese male was diagnosed as having SLE and his medical history revealed recurrent tonsillitis and pneumonia. He was diagnosed as having C3D because of undetectable serum C3 level. His parents were consanguineous. Sequence analysis of C3D cDNA revealed a homozygous deletion of exon 39 (84bp). A single base substitution (AG to GG) in the 3'-splice acceptor site of intron 38 was identified by sequencing the genomic DNA. Expression of C3Delta(ex39) cDNA, the C3cDNA lacking exon 39, in COS-7 cells revealed that C3Delta(ex39) was retained in endoplasmic reticulum-Golgi intermediate compartment because of defective secretion. These data indicate that a novel AG-->GG 3'-splice acceptor site mutation in intron 38 caused aberrant splicing of exon 39, resulting in defective secretion of C3.

Adult↗
PubMed2005

Angiosarcoma of the scalp treated with curative radiotherapy plus recombinant interleukin-2 immunotherapy.

PURPOSE: To evaluate the effectiveness of curative radiotherapy (RT) plus recombinant interleukin-2 (rIL-2) immunotherapy regarding the treatment results for angiosarcoma of the scalp. Curative resection of angiosarcoma of the scalp is usually difficult because of the diffuse, clinically undetectable local spread. RT is a rational therapeutic approach, because a wide region of the dermis can be treated, while sparing the underlying normal tissues. Recently, the effectiveness of immunotherapy with rIL-2 has also been reported in the treatment of angiosarcoma of the scalp. METHODS AND MATERIALS: The data of 20 patients with angiosarcoma of the scalp treated with curative RT plus rIL-2 immunotherapy between January 1988 and June 2002 were retrospectively analyzed. The total radiation dose was 70.3 +/- 6.9 Gy. The fractions were 2-3 Gy daily, given 5 d/wk. rIL-2 immunotherapy was performed by transcatheter arterial administration in 10 patients, systemic administration in 11 during the course of RT, and intratumoral injection in 10 during and/or after RT; 12 patients received a combination of two. Five patients underwent limited surgery, and concomitant pacilitaxel chemotherapy was also used in 2 patients. RESULTS: The median survival time for overall, local recurrence-free, and distant metastasis-free survival was 36.2, 11.1, and 17.8 months, respectively. Local recurrence developed in 7 patients (35%), 4 of whom also had evidence of distant metastases. An additional 7 patients (35%) developed distant metastases alone. Recurrence within the radiation field was recognized in 2 patients with systemic rIL-2 administration alone (p < 0.05). Arterial or intratumoral administration combined with systemic administration of rIL-2 resulted in better distant metaststasis-free survival rates (p < 0.05). CONCLUSION: Curative RT plus rIL-2 immunotherapy provided an efficient, effective means of treating angiosarcoma of the scalp. Arterial or intratumoral administration combined with systemic administration of rIL-2 may prolong survival. Additional studies with detailed treatment protocols are recommended.

Aged↗
PubMed2005

Concurrent double infections of the skin: phaeohyphomycosis and nocardiosis in a patient with idiopathic thrombocytopenic purpura.

We describe a case of concurrent double infection with phaeohyphomycosis and lymphocutaneous nocardiosis in an immunocompromised host. The episode occurred almost simultaneously with an incident of insect bites. Exophiala spinifera was isolated from lesions on the left arm and Nocardia asteroides was isolated from lesions on the right hand. Clinical resolution occurred within 5 months after initiation of antimicrobial treatment with oral itraconazole and minocycline. We believe that this case represents a novel episode of previously unreported concurrent infections with phaeohyphomycosis and lymphocutaneous nocardiosis in human beings.

Aged, 80 and over↗
PubMed2005

Cutaneous Scedosporium apiospermum infection in an immunocompromised patient and a review of the literature.

Scedosporium apiospermum (also known as Pseudallescheria boydii) is a ubiquitous filamentous fungus. This fungus is known as a cause of mycetoma, which may occur in a normally immune host following trauma. However, in an immunocompromised host, S. apiospermum may cause a life-threatening infection. We describe a case of S. apiospermum infection of the right hand in a patient who was receiving long-term immunosuppressants for adult Still's disease. We also review the cases of S. apiospermum infection with cutaneous manifestations reported between 1998 and 2003.

Aged↗
PubMed2005

Prevalence of atopic dermatitis and serum IgE values in nursery school children in Ishigaki Island, Okinawa, Japan.

There have been many studies of the prevalence of atopic dermatitis (AD), but few population-based epidemiologic studies measure the prevalence in Japan among children aged 5 years and younger. We examined the prevalence of AD, serum total IgE levels and specific IgE antibodies to 10 common allergens among children in Ishigaki Island, Okinawa, Japan in 2001. We also obtained information on the predictability of the U.K. Working Party diagnostic questionnaire criteria for AD in this population. Five hundred and sixty five children aged 5 years and younger were enrolled in this study with informed consent from their parents. The questionnaire of the U.K. Working Party diagnostic criteria for AD was translated into Japanese, and the parents completed the questionnaire sheet. Physical examination and blood sampling were done for all children. Thirty-nine out of the 565 (6.9%) children were diagnosed with AD by physical examination. The total and specific IgE levels were significantly higher in the children with AD than in those without AD. High levels of total IgE were found in 33.3% of the children with AD. A specific IgE to one or more allergens was detected in 64.1% of children with AD. However, a substantial population of children without AD also had high levels of total IgE (12.7%) and a specific IgE to one or more allergens (30.2%), and the increment of total and specific IgE levels was significantly associated with age. The percentage of positive answers to the questionnaire of the U.K. Working Party diagnostic criteria for AD was significantly higher in children with AD (59.0%) than in children without AD (5.3%) (P<0.0001). Its specificity was 94.7%. The false negative rate was 41%. In conclusion, the prevalence of AD was relatively low in children in Ishigaki Island. High levels of total IgE were found in only one third of children with AD under 5 years of age. The Japanese translated form of the questionnaire of the U.K. Working Party diagnostic criteria for AD should be refined to improve its sensitivity.

Child, Preschool↗
PubMed2005

[Evaluation of dermatological symptoms of Yusho patients in the annual examination in 2003-2004].

We evaluated the severity grades and the skin severity scores of the skin symptoms who visited the annual examinations of Fukuoka prefecture in 2003 and 2004. The severity of skin symptoms improved significantly in the first 20 years; nowadays, however, further improvement can hardly be observed. More than 36 years have passed since the Yusho incident, and about 60% of the patients currently present no skin symptoms. In contrast, in about 40% of the patients, characteristic skin symptoms of Yusho, such as pigmentation of skin, black comedones and acneform eruptions, could still be observed. Using Peason's correlation coefficient test and Spearman's correlation coefficient test, we analyzed correlation between "PCB pattern" and the blood PCB concentration, the skin severity grade and the skin severity scores. However, we could not find out any obvious correlation.

Biomarkers↗
PubMed2004

Role of c-Jun N-terminal kinase on lipopolysaccharide induced maturation of human monocyte-derived dendritic cells.

Dendritic cells (DCs) are potent antigen-presenting cells that play a pivotal role in the initiation of T cell-dependent immune responses. Immature DCs obtained from peripheral blood CD14+ monocytes by culture with granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) differentiate into mature DCs upon stimulation with lipopolysaccharide (LPS). At least three families of mitogen-activated protein kinases (MAPKs), that is, extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinases (JNK) and p38 MAPK, are involved in the DC maturation process. We report investigations of the role of JNK in the maturation of human monocyte-derived DCs. SP600125, a specific inhibitor of JNK, inhibited the LPS-induced up-regulation of CD80, CD83, CD86 and CD54, but augmented the up-regulation of HLA-DR. SP600125 slightly inhibited the down-regulation of FITC-dextran uptake during DC maturation. However, SP600125 did not affect the LPS induced up-regulation of allostimulatory capacity of DCs. SP600125 inhibited the release of IL-12 p70 and TNF-alpha from mature DCs. Although autologous T cells primed by the ovalbumin (OVA)-pulsed mature DCs produced IFN-gamma, but not IL-4, OVA-pulsed SP600125-treated mature DCs could initiate IL-4 production from autologous T cells. In contrast, a p38 MAPK inhibitor, SB203580, profoundly inhibited the phenotypic and functional maturation of DCs, while an ERK inhibitor, PD98059, had little or no effect. Taken together, the JNK signaling pathway appears to have a role that is distinct from the p38 MAPK and ERK cascades in the maturation process of DCs, and may be involved in the augmentation of Th2-prone T cell responses when it is suppressed.

Anthracenes↗
PubMed2004

PKC412 induces apoptosis through a caspase-dependent mechanism in human keloid-derived fibroblasts.

There is no established pharmacological therapy for skin keloids, a wound healing disorder. In this study, we investigated the effect of N-benzoyl staurosporine (PKC412), a protein kinase C inhibitor, on human keloid-derived fibroblasts to examine whether this agent is applicable for the treatment of keloid formation. Although PKC412 induced apoptosis in keloid fibroblasts in a time- and dose-dependent manner, the effective concentration of this agent was much higher than that of staurosporine. Western blotting showed that both PKC412 (10 microM) and staurosporine (100 nM) cleaved pro-caspase-3 to active forms. An in vitro caspase assay also showed that PKC412 and staurosporine elevated caspase-3 activities. Carbobenzoxy-Val-Ala-Asp-fluoromethyl ketone (Z-VAD-FMK), a caspase inhibitor with a broad spectrum, inhibited caspase-3 activities stimulated by PKC412 and staurosporine; however, only PKC412-induced apoptosis, but not staurosporine-induced apoptosis, was prevented by Z-VAD-FMK. These results suggested that PKC412-induced apoptosis, but not staurosporine-induced apoptosis, is mainly mediated by the caspase-dependent mechanism.

Apoptosis↗
PubMed2004

Formalin-fixed tumor cells effectively induce antitumor immunity both in prophylactic and therapeutic conditions.

BACKGROUND: Autologous whole tumor cell-based vaccinations would seem to be ideal since such vaccinations, in contrast to vaccination with a single defined antigen, have the potential to elicit a broad type of T-cell immune response to tumor-associated antigens. OBJECTIVE: We modified formaldehyde (formalin)-fixed mouse melanoma cells and investigated the utility of those cells as sources of tumor antigens for immunotherapy. METHODS: C57BL/6 or the proteasome activator PA28alpha-knockout mice were intradermally inoculated with 1% formalin-fixed B16 cells three times at weekly intervals either before or after tumor challenge. Simultaneously, interleukin-12 gene was transferred into the skin around immunization sites using gene gun technology. The effects were evaluated by tumor growth, antigen-specific interferon-gamma production in splenic lymphocytes, and activation of dendritic cells. RESULTS: Fixed cells directly induced production of tumor necrosis factor-alpha in dendritic cells more effectively than did frozen and thawed cells. More than 60% of the mice immunized with fixed cells and interleukin-12 rejected the challenged B16 tumor. CD4+ T cells from those mice produced a significant amount of interferon-gamma in response to melanoma cells. Furthermore, this combined treatment showed antitumor immunity initiated by CD8+ and CD4+ T cells in the therapeutic experiments. PA28alpha/beta appeared not to be required for the development of CD8+ T cells, although it is known to be essential for the development of CD8+ T cells specific for tyrosinase-related protein-2, one of melanocyte-lineage differentiated antigens. CONCLUSION: These results suggest that formalin-fixed autologous melanoma cells have a potential to function as effective antigen sources for immunotherapy.

Animals↗