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Masutaka Furue

Publications and source records attributed to Masutaka Furue.

At least 19 recordsLinked to original sources
PubMed2007

Expression of the p38 MAPK, NF-kappaB and cyclin D1 in extramammary Paget's disease.

BACKGROUND: The p38 mitogen-activated protein kinase (MAPK)/nuclear factor kappaB (NF-kappaB)/cyclin D1 signaling pathway has recently been shown to play an important part in the pathogenesis of many human tumors. However, the role of this signal transduction pathway in extramammary Paget's disease (EMPD) remains unknown. OBJECTIVE: This study was designed to investigate the expression of phosphorylated p38 MAP kinasealpha (p-p38 MAPKalpha), phosphorylated NF-kappa B p65 (p-NF-kappaB p65) and cyclin D1 proteins in EMPD and to evaluate the relationship among them. METHODS: Thirty-five tissue samples from 30 primary EMPD cases were analyzed by immunohistochemical staining in formalin-fixed, paraffin-embedded tissue sections for p-p38 MAPKalpha, p-NF-kappaB p65 and cyclin D1. RESULTS: Among the 35 specimens of EMPD, p-p38 MAPKalpha, p-NF-kappaB p65 and cyclin D1 were expressed in 30, 28 and 27, respectively. Moreover, in five metastatic lymph node specimens, all were positive for p-p38 MAPKalpha and p-NF-kappaB p65, four were positive for cyclin D1. There were significant correlations between expression of p-p38 MAPKalpha, p-NF-kappaB p65, and cyclin D1 in EMPD. CONCLUSION: This study provides evidence that p-p38 MAPKalpha, p-NF-kappaB p65, and cyclin D1 was overexpressed in EMPD, suggesting that the p38 MAPK/NF-kappaB/cyclin D1 signaling pathway might participate in the oncogenesis of EMPD.

Adult↗
PubMed2007

Expression and prognostic significance of Stat5a and E-cadherin in extramammary Paget's disease.

BACKGROUND: Stat5 has been shown to regulate the proliferation and inhibition of apoptosis in cancer cells. E-cadherin plays an important role in maintaining epithelial stability and is widely regarded as a prognostic marker in many types of human cancers. The expression of Stat5 has not been investigated in extramammary Paget's disease (EMPD). OBJECTIVES: To study the expression of Stat5a and E-cadherin protein in EMPD and to evaluate the relationships between them. METHODS: Thirty-six tissue samples from 34 cases with primary EMPD were subjected to immunohistochemical staining for Stat5a and E-cadherin. RESULTS: Twenty-nine of 30 in situ EMPD specimens were positive for Stat5a expression, and the staining pattern for Stat5a was mainly nuclear in the majority of Paget's cells. All four invasive specimens and two metastatic lymph node specimens were negative for Stat5a. Twenty-six of 30 in situ EMPD specimens expressed E-cadherin in more than 50% of tumor cells, and three of 30 in situ EMPD specimens expressed E-cadherin in less than 50% of tumor cells. One in situ EMPD specimen and one invasive specimen expressed E-cadherin in less than 25% of tumor cells. Three invasive specimens and two metastatic lymph node specimens were negative, with occasional membranous staining for E-cadherin. There is a significant correlation between the expression of Stat5a and E-cadherin. CONCLUSIONS: Our results showed that these proteins were found in in situ lesions, and it is speculated that these proteins may play some role in the prognosis/invasion of EMPD.

Aged↗
PubMed2006

A technique for identifying three diagnostic findings using association analysis.

In diagnosing diseases in clinical practice, a combination of three clinical findings is often used to represent each disease. This is largely because it is often difficult or impractical to assess for all possible combinations of symptoms and abnormal exam findings that occur in any particular disease. For most diseases, diagnostic triads are based on empirical observations. In this study, we determined diagnostic triads for chronic diseases using data mining procedures. We also verified the combinations' validity as well as our procedure for determining them. We used symptoms and examination findings from 477 patients with chronic diseases, collected as part of a 35-year longitudinal study begun in 1968. For each patient there were 295 items from examinations in internal medicine, dermatology, ophthalmology, dentistry and blood tests. We judged each item to be either normal or abnormal, and restricted the analysis to the abnormal findings. To analyze such an exhaustive assortment, we used the data mining technique of association analysis. The analysis generated three clinical findings for each disease. Diseases were defined based on blood tests. Searching through all 295 items to find the three most useful clinical findings would be impractical on a commodity PC. However, by excluding normal items, we were able to sufficiently reduce the total number of combinations so as to make combinatorial analysis on a PC feasible. In addition to more accurate diagnoses, we believe our technique can identify those diagnostic data that are more cost effective in terms of time and other resources required for their collection.

Data Collection↗
PubMed2006

Differential induction of Th1-prone immunity by human dendritic cells activated with Sporothrix schenckii of cutaneous and visceral origins to determine their different virulence.

Sporotrichosis is caused by a thermo-dependent dimorphic fungus, Sporothrix schenckii. The major clinical manifestations occur in the skin; however, cases of visceral manifestations have also been increasingly reported with some being observed in immune compromised patients. Different virulence of individual S. schenckii strain as well as immune status of the host could contribute to form such different clinical manifestations. Thus, the purpose of the study was to investigate whether different virulence of individual S. schenckii could be a factor for such clinical difference. We investigated the interactions between human monocyte-derived dendritic cells (MoDCs) and S. schenckii, assessed by (i) morphological features, (ii) surface marker expressions, cytokine productions, (iii) signaling pathways and (iv) allostimulatory activity of the activated MoDCs. Immature MoDCs, obtained from peripheral blood monocytes supplemented with granulocyte macrophage colony-stimulating factor and IL-4, were stimulated with S. schenckii strains of both yeasts and conidia forms of different origins (cutaneous isolates: KMU4649, IFM5906 and IFM46010; visceral isolates: KMU4648, IFM41598 and ATCC26331) to be used for various assays. Through the analysis, we found that the cutaneous S. shenckii of cutaneous origins were more potent to activate MoDCs to induce strong T(h)1 response, as evidenced by abundant IFN-gamma production, while the S. shenckii of visceral origins induced only minimal dendritic cell activation and T(h)1 induction. The p38 mitogen-activated protein kinase and c-Jun N-terminal kinase signaling pathways appeared to be associated with the differential activation of the MoDCs by S. schenckii of cutaneous and the visceral origins. Overall, we concluded that the differential activation of MoDCs by S. schenckii of cutaneous and visceral origins to induce T(h)1 response, other than immune status or the host, may be a factor for their different clinical manifestations.

Cell Differentiation↗
PubMed2006

Concentrations of polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and non-ortho and mono-ortho polychlorinated biphenyls in blood of Yusho patients.

We measured the concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), non-ortho polychlorinated biphenyls (non-ortho PCBs) and mono-ortho polychlorinated biphenyls (mono-ortho PCBs) in blood collected from 279 Yusho patients living in Japan, 92 Yusho-suspected persons living in Japan and 127 normal controls living in Fukuoka Prefecture, and compared among the groups in terms the concentrations of these compounds. The total toxic equivalents (TEQ) concentrations of PCDDs, PCDFs, non-ortho PCBs, and mono-ortho PCBs in the bloods of Yusho patients and Yusho-suspected persons were 161.4 and 51.2 pg TEQ/g lipid, respectively and were about 3.5 and 1.1 times higher than those of normal controls, respectively. Although the TEQ concentrations of PCDDs, non-ortho PCBs, and mono-ortho PCBs among Yusho patients, Yusho-suspected persons and normal controls were nearly the same, the PCDFs levels of Yusho patients were significantly higher than those of Yusho-suspected persons and about 10.3 times higher than those of normal controls. In Yusho patients, PCDFs contributed about 65% to the total TEQ concentration. Among the PCDFs congeners for Yusho patients, the concentration of 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) was about 11.3 times higher than that of normal controls. These findings indicated that Yusho patients even now, more than 34 years after the outbreak of Yusho, have much higher blood levels of 2,3,4,7,8-PeCDF in general than do unaffected persons.

Benzofurans↗
PubMed2006

Induction of efficient antitumor immunity using dendritic cells activated by recombinant Sendai virus and its modulation by exogenous IFN-beta gene.

Dendritic cell (DC)-based cancer immunotherapy has been paid much attention as a new and cancer cell-specific therapeutic in the last decade; however, little clinical outcome has been reported. Current limitations of DC-based cancer immunotherapy include sparse information about which DC phenotype should be administered. We here report a unique, representative, and powerful method to activate DCs, namely recombinant Sendai virus-modified DCs (SeV/DC), for cancer immunotherapy. In vitro treatment of SeV without any bioactive gene solely led DCs to a mature phenotype. Even though the expression of surface markers for DC activation ex vivo did not always reach the level attained by an optimized amount of LPS, superior antitumor effects to B16F1 melanoma, namely tumor elimination and survival, were obtained with use of SeV-GFP/DC as compared with those seen with LPS/DC in vivo, and the effect was enhanced by SeV/DC-expressing IFN-beta (SeV-murine IFN-beta (mIFN-beta)/DC). In case of the treatment of an established tumor of B16F10 (7-9 mm in diameter), a highly malignant subline of B16 melanoma, SeV-modified DCs (both SeV-GFP/DC and SeV-mIFN-beta/DC), but not immature DC and LPS/DC, dramatically improved the survival of animals. Furthermore, SeV-mIFN-beta/DC but not other DCs could lead B16F10 tumor to the dormancy, associated with strongly enhanced CD8+ CTL responses. These results indicate that rSeV is a new and powerful tool as an immune booster for DC-based cancer immunotherapy that can be significantly modified by IFN-beta, and SeV/DC, therefore, warrants further investigation as a promising alternative for cancer immunotherapy.

Adoptive Transfer↗
PubMed2006

COL7A1 mutation G2037E causes epidermal retention of type VII collagen.

COL7A1 glycine substitution (GS) mutations result in dominant and recessive dystrophic epidermolysis bullosa (DDEB and RDEB). Here, we report a DDEB family in which retention of type VII collagen by epidermal keratinocytes was observed for a female proband. Mutational analysis detected a GS mutation, G2037E, in the proband and her affected father. To demonstrate direct association of G2037E and type VII collagen retention we introduced this mutated COL7A1 gene into cultured keratinocytes using retroviral methods. This mutation was dominant, so we transferred a 1:1 mixture of wild-type (unaffected) and G2037E-mutated COL7A1, together, in addition to the unaffected gene or the mutated gene alone. The increase in type VII collagen cytoplasmic staining in the G2037E/wild transfectant cell samples was compared with that for control/wild-type cells. Intracellular collagen VII staining in the G2037E (alone)-transfected cells was even stronger than for the G2037E/wild transfection sample. These results indicate that the G2037E COL7A1 mutation leads to increased epidermal retention of type VII collagen in vivo, and also suggests that homozygotes carrying this dominant GS mutation may have more severe phenotypes than heterozygotes. This study furthers our understanding of GS COL7A1 mutations in DEB.

Collagen Type VII↗
PubMed2006

Proceedings of the 4th Georg Rajka International Symposium on Atopic Dermatitis, Arcachon, France, September 15-17, 2005.

The 4th Georg Rajka International Symposium on Atopic Dermatitis presented a comprehensive view of our current understanding and management of atopic dermatitis (AD). These proceedings highlight contributions related to the history of AD doctrines; genetic and epigenetic background; epidemiology; maturation of the immune system; infection and innate-adaptive immunity; epidermal inflammation, including neurogenic inflammation and pruritus; animal models; skin barrier; evidence-based therapy and education programs; prognostic and severity markers; and allergy testing. Several studies in animal models and human subjects point to impaired skin barrier function as a primary defect that facilitates the effect of environmental factors and immune dysregulation found in AD. The new frontier in AD therapy should, in the near future, reflect our better understanding of the skin barrier. The influence of environmental factors on the skin and other epithelial barriers in the perinatal period needs to be better understood to implement appropriate prevention programs.

Animals↗
PubMed2006

Chemical peeling by SA-PEG remodels photo-damaged skin: suppressing p53 expression and normalizing keratinocyte differentiation.

Chemical peeling with salicylic acid in polyethylene glycol vehicle (SA-PEG), which specifically acts on the stratum corneum, suppresses the development of skin tumors in UVB-irradiated hairless mice. To elucidate the mechanism through which chemical peeling with SA-PEG suppresses skin tumor development, the effects of chemical peeling on photodamaged keratinocytes and cornified envelopes (CEs) were evaluated in vivo. Among UVB-irradiated hairless mice, the structural atypia and expression of p53 protein in keratinocytes induced by UVB irradiation were intensely suppressed in the SA-PEG-treated mice 28 days after the start of weekly SA-PEG treatments when compared to that in the control UVB-irradiated mice. Incomplete expression of filaggrin and loricrin in keratinocytes from the control mice was also improved in keratinocytes from the SA-PEG-treated mice. In photo-exposed human facial skin, immature CEs were replaced with mature CEs 4 weeks after treatment with SA-PEG. Restoration of photodamaged stratum corneum by treatment with SA-PEG, which may affect remodeling of the structural environment of the keratinocytes, involved the normalization of keratinocyte differentiation and suppression of skin tumor development. These results suggest that the stratum corneum plays a protective role against carcinogenesis, and provide a novel strategy for the prevention of photo-induced skin tumors.

Animals↗
PubMed2006

Pneumatosis cystoides intestinalis with systemic sclerosis, limited type resulting in a poor prognosis.

Pneumatosis cystoides intestinalis (PCI) is a rare disease characterized by the presence of multilocular intramural clusters of gas in the alimentary tract and has been considered to have a favorable response to conservative treatment. We describe the first case of limited type of systemic sclerosis (SSc) with PCI. A 74-year-old Japanese woman presented with a 4-month history of an unhealed cutaneous ulcer on the right third finger, along with sclerodactyly of bilateral hands. Proximal skin sclerosis was absent. The patient reported acute abdominal pain, and a diagnosis of PCI was established on plain radiography. The patient died of multiple organ failure 5 months after the development of PCI. PCI is rarely complicated with SSc, and all cases previously reported were associated with diffuse SSc. Because PCI is one of the poor prognostic factors of SSc, we should recognize the presence of this condition even in patients with limited cutaneous involvement.

Aged↗
PubMed2006

A case of genital folliculosebaceous cystic hamartoma with an unique aggregated manifestation.

Folliculosebaceous cystic hamartoma (FCH) is a recently recognized cutaneous hamartoma composed of follicular, sebaceous and mesenchymal components, and usually occurring on the head and neck. We describe herein a case of FCH with an unique aggregated manifestation in a genital lesion. The patient was a 40-year-old woman with a genital lesion composed of a pedunculated nodule, a dome-shaped nodule and a subcutaneous nodule, measuring 5 cm in the greatest dimension. The largest, pedunculated nodule was histologically composed of an infundibulo-cystic structure with follicular, sebaceous and mesenchymal elements accompanied by cystic structures of various sizes lined by stratified squamous epithelium and follicular germinative cells suggesting follicular cysts. The dome-shaped nodule consisted of anastomosing strands of epithelial cells with follicular components. The subcutaneous nodule had two components, an infundibulo-cystic structure and a cyst lined by squamous epithelium. In our case, the unusual clinical feature of large and multiple nodules was due to the presence of several prominent hamartomatous cystic structures with FCH. This is the third case of giant FCH. The clinical presentation and location of giant FCH is unusual.

Adult↗
PubMed2006

Anti-CXCR3 staining is useful for detecting human cutaneous and mucosal mast cells.

Human synovial mast cells (MC) can be immunolabelled with antihuman CXCR3 antibody (Ab) (clone 49801). We have investigated whether cutaneous and mucosal MC are stained with anti-CXCR3 Ab in paraffin-embedded sections. Immunohistochemical staining and immunofluorescence double staining assays were performed with anti-CXCR3, anti-tryptase, and anti-chymase Ab using normal skin, psoriatic skin lesions, and normal colon. When compared with tryptase and chymase staining, 100% of the cutaneous and 98% of the mucosal MC were positive for CXCR3. Anti-CXCR3 staining is a useful marker for human cutaneous and mucosal MC in paraffin-embedded sections.

Antibodies, Monoclonal↗
PubMed2006

Pressure cutaneous ulcer over a pacemaker successfully treated with left subcostal transplantation in an extremely thin patient.

Implantation of a permanent cardiac pacemaker is becoming common with the increase in the elderly population. A cutaneous ulcer over the pacemaker is a rare complication. Most such cases previously reported demonstrate non-specific granuloma histologically, negative patch testing of materials used in the device, and no growth in the bacterial culture taken from the generator pocket. To date, the conventional treatments often result in a disappointing outcome. We describe an extremely thin 79-year-old Japanese male with a pressure cutaneous ulcer caused by the presence of a pacemaker device. This patient was referred to us with a 1-month history of repeated cutaneous ulcer and exposure of the cardiac pacemaker in the left pectoral area. Conservative treatment was not effective. Treatment with left subcostal implantation of a new pacemaker, which was not wrapped, and disposition of the electrodes in the subcutaneous tissue of the thorax was successful. Cutaneous manifestations have not recurred for 5 years. Considering the poor condition of the patient, subcostal translocation of the pacemaker was a simple and acceptable treatment for pressure cutaneous ulcer over the pacemaker.

Aged↗
PubMed2006

Expression of p16 and hTERT protein is associated with the presence of high-risk human papillomavirus in Bowenoid papulosis.

BACKGROUND: High-risk human papillomavirus (hrHPV) type E6 and E7 oncoproteins contribute to oncogenesis in multiple ways by modulating the activities of host components in cell-cycle regulation including the expression of p16 protein (p16) and human telomerase reverse transcriptase (hTERT). The expression of p16 and hTERT protein in Bowenoid papulosis (BP) has not been studied. METHODS: Biopsy samples of BP from 26 patients were subjected to in situ hybridization for various HPV strains and immunohistochemical staining for p16 and hTERT. RESULTS: Among the 26 biopsy specimens, in situ hybridization using DNA probes for HPV 16/18 revealed positivity in 18 specimens (69.2%), one of which also showed positivity with the probes for HPV 6/11. HPV 31/33/35 was found in three specimens (11.5%). Two specimens (7.7%) were positive for unclassified HPV. Twenty-one BP specimens that were infected with hrHPV were positive for p16 and/or hTERT. Moderate or strong and diffuse immunostaining was observed for p16 in 15 hrHPV-infected specimens and for hTERT in 16 hrHPV-infected specimens. The expression of p16 or hTERT was each significantly associated with the presence of hrHPV. CONCLUSIONS: hrHPVs were involved in inducing p16 and hTERT overexpression in BP. Moreover, our results suggested that immunohistochemical p16 and hTERT expression might be a useful marker of hrHPV infection in BP.

Adult↗