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Biomedical subjects

M Furue

Publications and source records attributed to M Furue.

At least 55 records · Page 3Linked to original sources

Co-expression of thymidine phosphorylase and heme oxygenase-1 in macrophages in human malignant vertical growth melanomas.

Expression of thymidine phosphorylase (TP) is often associated with tumor angiogenesis and / or prognosis in patients. Further, infiltration of macrophages is closely correlated with the depth of tumor and angiogenesis in melanomas. In this study, we examined the expression of TP and an activated macrophage-specific enzyme, heme oxygenase-1 (HO-1), involved in malignancy in 22 cases with melanomas. TP was strongly expressed not only in CD68-positive macrophages in and around tumors, but also in S100 protein-positive melanoma cells, fibroblasts and keratinocytes. By contrast, HO-1 was specifically expressed in macrophages, but only slightly in melanoma cells and other cell types in the stroma of melanomas. We thus observed apparent co-expression of TP and HO-1 in macrophages infiltrating in the late stage of malignant melanomas. There appeared increasing numbers of TP-positive cells in Clark level IV and V melanoma compared with Clark level I (in situ) melanoma, and there was also a close correlation between numbers of TP-positive cells and HO-1-positive cells. Both TP- and HO-1-positive macrophages could be observed in the stroma in and around tumors in vertical growth melanomas.

Antigens, CD↗

A case of CD56+ cutaneous aleukaemic granulocytic sarcoma with myelodysplastic syndrome.

We describe a 70-year-old man with cutaneous granulocytic sarcoma who presented with numerous cutaneous nodules but without any leukaemic involvement of the peripheral blood. The tumour cells were positive for lysozyme, peroxidase, CD11a, CD11c, CD33 and HLA-DR, and weakly positive for CD4 and CD14, suggesting granulocytic differentiation. The bone marrow at admission showed dysplasia of the erythrocytic and granulocytic lineage and complex chromosomal abnormalities in association with an increase in monocytes. The patient was diagnosed as having granulocytic sarcoma of monocytic lineage with concomitant myelodysplastic syndrome. In this case, tumour cells also expressed the neural cell adhesion molecule (CD56), which has been suggested as a possible risk factor for developing granulocytic sarcoma in acute myelogenous leukaemia.

Aged↗

Suppressive effect of topically applied CX-659S, a novel diaminouracil derivative, on the contact hypersensitivity reaction in various animal models.

BACKGROUND: The T-cell-mediated contact hypersensitivity reaction (CHR) is thought to be involved in the pathogenesis of clinical cutaneous disorders including atopic dermatitis. A novel diaminouracil derivative, CX-659S, has been reported to have an inhibitory activity against picryl chloride (PC)-induced CHR when administered either orally or percutaneously. The inhibitory effect of topical CX-659S was assessed in three CHR models in the present study. In addition, to elucidate the mechanism of action of this compound, we examined the effect of CX-659S on the expression of messenger RNAs for proinflammatory cytokines after elicitation in PC models. METHODS: For the in vivo evaluation of the efficacy of CX-659S, we used PC- or oxazolone-induced CHR in mice and 2,4-dinitrochlorobenzene (DNCB)-induced CHR in guinea pigs. CX-659S was topically applied immediately after the hapten challenge in each model. To assess the effect on gene expression of cytokines, we used the reverse transcriptase-polymerase chain reaction (RT-PCR), a semiquantitative technique with specific primers. RESULTS: Topical CX-659S dose-dependently inhibited ear swelling at 24 h after the challenge in the two mouse models. This inhibitory effect was histologically confirmed in the PC model. Topically applied CX-659S also inhibited erythema and edema formation 24 h after challenge in the guinea pig model. CX-659S inhibited the expression of mRNA for proinflammatory cytokines IL-1 beta and TNF-alpha in vivo. CONCLUSIONS: Topically applied CX-659S showed significant inhibitory activities against CHR models both in mice and in guinea pigs. Inhibition profiles of CX-659S toward mRNA expression for proinflammatory cytokines corroborated these findings. CX-659S thus could be a useful therapeutic agent for allergic cutaneous disorders such as allergic contact dermatitis and atopic dermatitis.

Administration, Topical↗

Clinical, immunological and MRI features of myelitis with atopic dermatitis (atopic myelitis).

In order to clarify the characteristic features of myelitis with atopic dermatitis (AD), we compared the clinical, immunological and MRI findings between 14 myelitic patients with AD and 12 myelitic patients without AD. The myelitic patients with AD showed the following distinct features, compared with those without AD. (1) A preferential involvement of the cervical cord, as shown by neurologic as well as MRI examinations (14/14 vs. 5/12; P=0.0012), (2) paresthesia/dysesthesia as the predominant symptoms and a rare occurrence of definite muscle weakness (0/14 vs. 5/12; P=0.0120) and dysuria (1/14 vs. 8/12; P=0.0029), (3) a lower Expanded Disability Status Scale score (mean, 1.5 vs. 3.5; P=0.0018), (4) normal cerebrospinal fluid (CSF) findings including those for the IgG index and oligoclonal IgG bands and (5) a persistence of neurologic symptoms and MRI lesions during the follow-up periods (mean, 17 months). In addition, both the serum total IgE level and the frequency of specific IgE to Dermatophagoides farinae were significantly higher in the myelitic patients with AD (median IgE=1266 U/ml, specific IgE 14/14) than in those without AD (145 U/ml, P=0.0034 and 8/12, P=0.0331, respectively) and in 40 healthy controls (86 U/ml, P<0.0001 and 12/40, P<0.0001, respectively). Since myelitis with AD has distinct features and atopy to mite antigens appears to be the underlying cause of this condition, it may therefore be a distinct subtype of myelitis.

Acute Disease↗

Effects of hepatocyte growth factor (HGF) and activin A on the morphogenesis of rat submandibular gland-derived epithelial cells in serum-free collagen gel culture.

To study the mechanisms of morphogenesis in salivary gland regeneration, we have established the RSMG-1 cell line derived from submandibular gland (SMG) of 10-wk-old Wistar female rats in serum-free culture. Our finding that RSMG-1 cells originated from duct cells was based on morphology and immunohistochemical results. In three-dimensional serum-free collagen gel culture, HGF induced branching morphogenesis of RSMG-1 cells. Histological examination revealed that HGF-induced branching structure exhibited well-formed lumina. This morphology closely resembles that found in vivo. The cells also expressed activin A. Exogenously added activin A at a high concentration reduced HGF-induced branching morphogenesis. These findings suggest that the morphogenesis of the salivary gland is modulated by HGF and activin A. Our results show that the RSMG-1 cell line may be useful in studies of salivary gland regeneration.

Activins↗

A progression to dermatofibrosarcoma protuberans with a fibrosarcomatous component: a special reference to the chromosomal aberrations.

Dermatofibrosarcoma protuberans (DFSP) with fibrosarcomatous areas (DFSP-FS) is differentiated from ordinary DFSP by its unfavourable prognosis. We carried out sequential analysis of numerical chromosomal abnormalities in two cases of DFSP during their progression to metastatic disease with FS areas (DFSP-M-FS). They were compared with nine cases of ordinary DFSP and three cases of DFSP-FS, but without metastases. Numerical chromosomal changes were examined by fluorescence in situ hybridization (FISH) using alpha-satellite centromeric probes for chromosomes 1, 8, 11 and 17. Numerical imbalances of chromosome 1 were not clarified. A gain of chromosome 8 was demonstrated in the two cases of DFSP-M-FS. A gain of chromosome 11 was observed in one of the two cases of DFSP-M-FS and in one case of DFSP-FS. A gain of chromosome 17 was demonstrated in both metastatic tumours and in recurrent tumours in two cases of DFSP-M-FS, in addition to two cases of DFSP-FS and four cases of ordinary DFSP with recurrent tumours or large tumours. This study raised the hypothesis that a gain of chromosome 17 developed in recurrent or large-sized DFSP, which occurs in high-risk groups with the possibility of a progression to FS.

Adolescent↗

Reduced amount of secretory component of IgA secretion in tears of patients with atopic dermatitis.

Coupled with the previous finding that sIgA excretion was reduced onto the surface of the skin, we demonstrated that sIgA secretion in the tears of patients with atopic dermatitis (AD) was significantly lower than that of normal subjects, using a small stick made of nitrocellulose membrane. In the bacterial cultures, we have also detected a higher frequency of Staphylococcus aureus in the tears from patients with AD compared to normal subjects. These findings suggested reduced sIgA secretion on the mucous membrane might play a crucial role in the pathomechanisms of the ocular lesions, such as abnormal bacterial flora and ocular complications as well as the establishment of skin lesions in AD.

Adolescent↗

Migration of Langerhans cells in an in vitro organ culture system: IL-6 and TNF-alpha are partially responsible for migration into the epidermis.

Although it is well established that epidermal Langerhans cells (LC) originate from bone marrow, little is known about the mechanism of this migration into the epidermis from bone marrow. In order to clarify the mechanism of this migration, we constructed an in vitro model. LC were depleted by daily topical application of clobetazole propionate (CP) solution onto the ear of Balb/c mice. Seven days later, ear skin was cut off, separated and co-cultured dermal-side-up with syngeneic (Balb/c), semisyngeneic ((C3H x Balb/c)F1), or allogeneic (C3H) epidermal cells (EC) for 3 days. We found (1) that a marked migration of donor LC into the recipient epidermis was observed in the LC-depleted skin, (2) that only syngeneic LC actively migrated into the recipient epidermis; however, the migration of semisyngeneic and allogeneic LC was detected at very low levels, (3) that the migratory capacity of donor LC was directly proved by a biolabeling technique using donor EC labeled with PKH-26, and (4) that anti-IL-6 and anti-TNF-alpha antibodies inhibited the migration of donor LC into the recipient epidermis. These data demonstrate that the resident LC have the potential to traffic through the dermis into the epidermis in a highly syngeneic-specific fashion, and that IL-6 and TNF-alpha are partially responsible for promoting this migration.

Animals↗

Activation pattern of Langerhans cells in the afferent and efferent phases of contact hypersensitivity.

Langerhans cells are MHC class II (Ia) positive antigen-presenting cells that play a crucial role in the induction of contact hypersensitivity (CHS). The topical application of a hapten modifies the cell surface moieties of Langerhans cells, and activates Langerhans cells to increase their size and Ia intensity. The haptenated and activated Langerhans cells emigrate from the epidermis and thus the in situ density of Langerhans cells usually decreases during 24-48 h after the hapten application in CHS. To determine whether the early activation pattern of Langerhans cells is different between the afferent phase and the efferent phase of CHS, we compared the density and morphologic changes of Langerhans cells in CHS to trinitrochlorobenzene using nonsensitized and sensitized mice. We found that the application of a hapten induces more significant enlargement of Langerhans cell size in the afferent phase than in the efferent phase, whereas the reduction of Langerhans cell density is more marked in the efferent than in the afferent phase of CHS. Moreover, topical immunosuppressive drugs inhibit the in situ activation of Langerhans cells.

Animals↗

Molecular mechanisms involved in the migration of epidermal dendritic cells in the skin.

The murine epidermis contains two types of dendritic cells (DC), Thy-1+ dendritic epidermal T cells (DETC) and Langerhans cells. In this review, we introduce our data obtained using a skin organ culture system to examine the migratory capacity of DETC and Langerhans cells into the epidermis. DETC or Langerhans cells were depleted by topical application ofclobetazole propionate (CP) solution onto the murine ears. CP-treated or untreated ear skin was co-cultured with syngeneic (semi-syngeneic, or allogenic, in experiments with Langerhans cells) epidermal cell suspension. We found (i) that donor DETC or Langerhans cells migrated into the CP-treated epidermis as well as into untreated epidermis, (ii) that leukosialin Ly48 recognized by monoclonal antibody S11 and TNF-alpha strongly inhibited donor Langerhans cell migration into the epidermis. We mention other molecules that may participate in the migration of Langerhans cells such as chemotactic cytokines, monocyte chemoattractant protein (MCP)-1, TGF-beta and skin-homing molecule, cutaneous lymphocyte-associated antigen (CLA) on Langerhans cells.

Animals↗

Soluble E-selectin and eosinophil cationic protein are distinct serum markers that differentially represent clinical features of atopic dermatitis.

The serum levels of eosinophil cationic protein (ECP), soluble E-selectin (sE-selectin), soluble CD14 (sCD14) and interleukin (IL)-4 are known to be elevated in patients with atopic dermatitis (AD). However, little is known of the mutual relationship between these factors. To elucidate the clinical and mutual relevance of these markers, we examined the serum levels of ECP, sE-selectin, sCD14 and IL-4 as compared with eruption scores, itch scores, total IgE and numbers of peripheral eosinophils in patients with AD (n = 43), non-atopic eczema (n = 24) and urticaria (n = 13) and in normal individuals (n = 45). In 27 patients with AD the levels of these markers were compared before and after treatment. Levels of ECP were elevated only in the patients with AD, whereas the sE-selectin levels were higher not only in AD but also in non-atopic eczema in a severity-dependent manner. The levels of both markers significantly diminished after treatment. Significant correlations existed between ECP levels and numbers of eosinophils, sE-selectin levels and itch scores, and sE-selectin levels and IgE levels. No significant changes were observed in the sCD14 and IL-4 levels. Taken together, sE-selectin and ECP are good but distinct serum markers that reflect different clinical features of AD.

Adolescent↗

Expression of tetraspans transmembrane family in the epithelium of the gastrointestinal tract.

Tetraspans transmembrane family (TSTF) members, also known as tetraspanin superfamily, have various effects on cell proliferation, motility, and adhesion not only in hematopoietic cells, but also in other type of cells. However, little is known about their expression in the human gastrointestinal (GI) tract. The authors characterized immunohistologically the localization of six members of TSTF (CD9, CD37, CD53, CD63, CD81, and CD82) in the normal epithelium from esophagus to colon. CD9 and CD82 molecules were strongly expressed in all epithelial surface membranes, from esophagus to colon, and their staining pattern was quite similar. Expression of CD37 was not detectable throughout the GI tract. Expression of CD53 was barely detectable. Expression of CD63 was clearly detected distal to the stomach, including the duodenum, small intestine, and colon. On the contrary, expression of CD81 was detected only in the esophagus--confined to a few layers from the basal layer. From these data it seems likely that the expression of TSTF molecules might be regulated differentially depending on the site of the GI tract.

Adult↗

Gamma-irradiation deregulates cell cycle control and apoptosis in nevoid basal cell carcinoma syndrome-derived cells.

The nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by nevi, palmar and plantar pits, falx calcification, vertebrate anomalies and basal cell carcinomas. It is well known in NBCCS that gamma-irradiation to the skin induces basal cell carcinomas or causes an enlargement of the tumor size, although the details of the mechanism remain unknown. We have established lymphoblastoid cell lines from three NBCCS patients, and we present here the first evidence of abnormal cell cycle and apoptosis regulations. A novel mutation (single nucleotide deletion) in the coding region of the human patched gene, PTCH, was identified in two sibling patients, but no apparent abnormalities were detected in the gene of the remaining patient. Nevertheless, the three established cell lines showed similar features in the following analyses. Flow cytometric analyses revealed that the NBCCS-derived cells were accumulated in the G2M phase after gamma-irradiation, whereas normal cells showed cell cycle arrest both in the G0G1 and G2M phases. The fraction of apoptotic cells after gamma-irradiation was smaller in the NBCCS cells. The level of p27 expression markedly decreased after gamma-irradiation in the NBCCS cells, although the effects of the irradiation on the expression profiles for p53, p21 and Rb did not differ in normal and NBCCS cells. These findings may provide a clue to the molecular mechanisms of tumorigenesis in NBCCS.

Adolescent↗