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Biomedical subjects

N Matsuyoshi

Publications and source records attributed to N Matsuyoshi.

33 records · Page 2Linked to original sources
PubMed1995

Effect of cytotoxic prostaglandin, delta 12-prostaglandin J2 on E-cadherin expression in transformed epidermal cells in culture.

The cyclopentenone prostaglandins (PGs), such as delta 12-PGJ2 and PGA1, are potent inhibitors of growth in a variety of cultured cells, including human epidermal cells. To clarify the mechanism of the cytotoxicity of these PGs, we examined the effects of delta 12-PGJ2 on the function and expression of E-cadherin, which plays a major role in the maintenance of intercellular adhesion, in transformed human epidermal cells in culture (HSC-1). A 12-h incubation with 5 micrograms/ml of delta 12-PGJ2 did not affect the cell-binding activity of E-cadherin expressed in HSC-1 cells. Immunoblot analysis using a monoclonal antibody specific to human E-cadherin revealed that a 12-h incubation with 5 micrograms/ml of delta 12-PGJ2 induced E-cadherin expression in HSC-1 cells. Immunofluorescence using a monoclonal antibody against human E-cadherin demonstrated that E-cadherin was localized to the cell-cell contact regions in HSC-1 cells. Following a 12-h incubation with 5 micrograms/ml of delta 12-PGJ2, E-cadherin was also detected in a uniform pattern along cell junctions, although cell morphology was changed by the presence of cytotoxic PGs. These results suggest that the cytotoxicity of cyclopentenone PGs is related, at least in part, to E-cadherin expression in transformed human epidermal cells.

Antibodies, Monoclonal↗
PubMed1995

Association of p120, a tyrosine kinase substrate, with E-cadherin/catenin complexes.

p120 was originally identified as a substrate of pp60src and several receptor tyrosine kinases, but its function is not known. Recent studies revealed that this protein shows homology to a group of proteins, beta-catenin/Armadillo and plakoglobin (gamma-catenin), which are associated with the cell adhesion molecules cadherins. In this study, we examined whether p120 is associated with E-cadherin using the human carcinoma cell line HT29, as well as other cell lines, which express both of these proteins. When proteins that copurified with E-cadherin were analyzed, not only alpha-catenin, beta-catenin, and plakoglobin but also p120 were detected. Conversely, immunoprecipitates of p120 contained E-cadherin and all the catenins, although a large subpopulation of p120 was not associated with E-cadherin. Analysis of these immunoprecipitates suggests that 20% or less of the extractable E-cadherin is associated with p120. When p120 immunoprecipitation was performed with cell lysates depleted of E-cadherin, beta-catenin was no longer coprecipitated, and the amount of plakoglobin copurified was greatly reduced. This finding suggests that there are various forms of p120 complexes, including p120/E-cadherin/beta-catenin and p120/E-cadherin/plakoglobin complexes; this association profile contrasts with the mutually exclusive association of beta-catenin and plakoglobin with cadherins. When the COOH-terminal catenin binding site was truncated from E-cadherin, not only beta-catenin but also p120 did not coprecipitate with this mutated E-cadherin. Immunocytological studies showed that p120 colocalized with E-cadherin at cell-cell contact sites, even after non-ionic detergent extraction. Treatment of cells with hepatocyte growth factor/scatter factor altered the level of tyrosine phosphorylation of p120 as well as of beta-catenin and plakoglobin. These results suggest that p120 associates with E-cadherin at its COOH-terminal region, but the mechanism for this association differs from that for the association of beta-catenin and plakoglobin with E-cadherin, and thus, that p120, whose function could be modulated by growth factors, may play a unique role in regulation of the cadherin-catenin adhesion system.

Binding Sites↗
PubMed1995

Bilateral inguinal scrofuloderma during steroid therapy in a patient with bullous pemphigoid.

This report described a case of scrofuloderma that developed in the bilateral inguinal regions during treatment of bullous pemphigoid with systemic corticosteroid. Analysis of the literature on scrofuloderma between 1978-1993 disclosed that the number of cases with extracervical involvement are increasing. Immunosuppression could disseminate tuberculous focuses, resulting in extracervical involvement of SD connected with the underlying extrapulmonary tuberculous lesions.

Aged↗
PubMed1995

Soluble E-cadherin: a novel cutaneous disease marker.

E-cadherin is a major homophilic cell-cell adhesion molecule of the skin. There are two forms of E-cadherin--membrane and soluble types. Although various abnormalities of the former type have been identified in some cutaneous diseases, information relating to the latter is sparse. We measured the concentrations of soluble E-cadherin in several cutaneous diseases, and found higher levels in sera from patients with bullous pemphigoid, pemphigus vulgaris, psoriasis vulgaris and inflammatory skin diseases, compared with controls. In psoriasis vulgaris the levels of soluble E-cadherin in sera correlated with the PASI score. In normal individuals, levels in suction blister fluid were double those in sera. These findings suggest that changes occur in circulating levels of soluble E-cadherin in skin disease, possibly reflecting increased turnover and/or proteolysis of cell-surface molecules in the epidermis.

Biomarkers↗
PubMed1994

Cadherins in cutaneous biology.

The role of cadherins in cutaneous biology has focused mainly on the classical cadherins, E- and P-cadherin. In this review, roles for cadherins in skin morphogenesis, keratinocyte differentiation, and cancer metastasis are discussed. E-cadherin is expressed on the surfaces of whole epidermal layer cells, and P-cadherin is expressed only on the surfaces of basal cells. Ultrastructural studies have shown that E-cadherin is distributed on the cytoplasmic membranes of keratinocytes with a condensation in the intercellular space of the desmosomes. During human skin development, P-cadherin expression is spatiotemporally controlled and closely related to the segregation of basal layers as well as to the arrangement of epidermal cells into eccrine ducts. In human skin diseases, E-cadherin expression is markedly reduced on the acantholytic cells of tissues in pemphigus and also in Darier's disease. Keratinocytes cultured in high calcium produce a much more intense immunofluorescence of intercellular E- and P-cadherin than do cells grown in low calcium. Ultrastructural studies show that E-cadherin on the cytoplasmic membrane of the keratinocytes is shifted to desmosomes under physiological conditions and therein expresses an adhesion function is association with other desmosomal cadherins. Cell adhesion molecules are now considered to play significant roles in the cellular connections of cancers and metastatic cells. Reduced expression of E-cadherin on invasive neoplastic cells has been demonstrated for cancers of the stomach, liver, breast, and several other organs. This reduced expression of E-cadherin is observed in squamous cell carcinoma and Paget's disease. Soluble E-cadherins in sera are elevated in various skin diseases, including bullous pemphigoid, pemphigus vulgaris and psoriasis, but not in patients with burns. Markedly high levels in soluble E-cadherin are demonstrated in patients with metastatic cancers.

Cadherins↗
PubMed1994

Production of monoclonal antibodies against the N-terminal noncollagenous domain of type VII collagen encoded by epidermolysis bullosa acquisita antigen cDNA.

Eleven monoclonal antibodies were produced against the human N-terminal noncollagenous domain of type VII collagen. All antibodies were specifically bound to the epidermal basement membrane zone and did not cross-react with other dermal collagens. A binding of these antibodies was investigated with various species and revealed that the reactivities of each monoclonal antibody against rat, mouse, human and guinea pig skin differ from each other. These data may suggest that type VII collagen is antigenic to immunized small animals, i.e. the rat and mouse, and that there are multiple antigenic determinants on type VII collagen.

Animals↗
PubMed1994

Reactivation of phototoxicity test for psoralens plus ultraviolet A by low-dose methotrexate.

Reactivation of a solar burn has been reported after administration of methotrexate for cancer and psoriasis patients. We report a case of psoriasis with a similar but delayed elicitation of phototoxic reaction by administration of low-dose methotrexate one month after psoralen and long-wave ultraviolet light (PUVA) treatment. The reactivation was seen in an already receding phototoxicity test area but not in a less phototoxic, noninterval PUVA treated area, suggesting that the reactivation by methotrexate is related with the severity of light-induced skin inflammation.

Aged↗
PubMed1993

Expression of E-cadherin cell adhesion molecules in human breast cancer tissues and its relationship to metastasis.

E-cadherin (E-cad) is a subclass of the cadherin family that plays a major role in maintenance of intercellular junctions in epithelial tissues. In order to explore the correlation between the expression of E-cad and cancer invasion and metastasis in vivo, we performed an immunohistochemical examination for E-cad expression in 120 patients with breast cancer using our specific anti-E-cad monoclonal antibody. In noncancerous epithelial cells, E-cad was strongly expressed on cell-cell boundaries, whereas various staining patterns were observed in tumors. Of these 120 tumors, 56 (47%) showed Pr type expression of E-cad, and 64 (53%) showed Rd type or negative expression. We found significant correlations between E-cad expression and clinicopathological features. The frequency of Rd type was significantly higher in invasive ductal carcinomas (58%, 56 of 97) and poorly differentiated carcinomas (84%, 21 of 25) than in noninvasive and well-differentiated carcinomas. Furthermore, a high frequency of Rd type was detected in the following advanced tumors: T3,4 tumors, 71% (22 of 31); tumors with extensive lymph node metastasis, 74% (29 of 39); and tumors with distant metastasis, 86% (19 of 22). These values were significantly higher compared with their counterparts. The expression of epidermal growth factor receptor tended to be positive in E-cad-positive tumors. However, no significant relationship was seen among E-cad expression, menopausal status, hormone receptor status, and DNA ploidy pattern. These results suggest that the reduction of E-cad expression may play an important role in invasion and metastasis of human breast cancer.

Adult↗
PubMed1993

p60v-src causes tyrosine phosphorylation and inactivation of the N-cadherin-catenin cell adhesion system.

Transformation of chick embryonic fibroblasts with Rous sarcoma virus strongly suppresses N-cadherin-mediated cell-cell adhesion, without inhibiting its expression. This suppression is correlated with tyrosine phosphorylation of N-cadherin and catenins, the cadherin-associated proteins, which are known to regulate cadherin function. Experiments with non-myristylation and temperature-sensitive mutants of RSV and with herbimycin A, a potent inhibitor of tyrosine kinases, suggest that both the suppression of cell adhesion and tyrosine phosphorylation of catenins are highly transformation-specific.

Animals↗
PubMed1993

Relationship between heat shock protein induction and the binding of antibodies to the extractable nuclear antigens on cultured human keratinocytes.

The importance of environmental factors such as ultraviolet light and temperature in the pathogenesis of cutaneous lupus erythematosus is well recognized. Recent evidence suggests the presence of autoantibodies to heat shock proteins (HSP) in the sera and enhanced expression of the HSP70 gene in peripheral blood mononuclear cells of patients with systemic lupus erythematosus. We designed experiments to determine how HSP or stress protein inducers affect the cell surface binding of IgG antibodies from sera containing anti-SS-A/Ro and anti-ribonuclear protein (RNP) antibodies to keratinocytes because these antibodies are considered to be one of the immunologic triggers of cutaneous lupus erythematosus. Immunofluorescence and immunoblot analysis using a monoclonal antibody to the 72 kDa of HSP revealed that an 18-h incubation with 10 micrograms/ml of delta 12-PGJ2, one of cytotoxic prostaglandins, induced HSP72 formation in cultured human keratinocytes. delta 12-PGJ2 augmented the binding of IgG antibodies from sera containing anti-U1RNP and anti-SS-A/Ro antibodies to cultured keratinocytes, but produced no enhancement of the binding of IgG antibodies from sera containing anti-Sm or anti-DNA antibodies. Similar results were also obtained by using flow cytometry analysis. HSP was also induced by ultraviolet B irradiation. These results suggest that exposure of keratinocytes to stressors such as delta 12-PGJ2 and ultraviolet light increases the binding sites for U1RNP,SS-A/Ro, and SS-B/La antibodies. The association between HSP induction and the appearance of extractable nuclear antigens may provide a better understanding of why environmental stimuli can promote the development of erythematous lesions in the skin.

Antigens, Nuclear↗
PubMed1992

Immunohistochemical evaluation of E-cadherin adhesion molecule expression in human gastric cancer.

E-cadherin (ECD) is one of subclasses of the cadherin family which plays a major role in the maintenance of intercellular adhesion in epithelial tissues. An immunohistochemical study of ECD expression was performed on gastric adenocarcinoma from 103 patients using our monoclonal antibody for human ECD (HECD-1). ECD was strongly expressed in normal gastric epithelium without exception; however, various staining patterns were observed in cancer tissues. The frequency of tumours with preserved ECD expression (Pre-type) and reduced ECD expression (Rd-type) was 42% and 58% respectively. Tumours with a high frequency of Rd-type expression particularly included: undifferentiated tumours (85%, 46/54), Borrmann's type 4 (90%, 9/10), tumours larger than 2.6 cm in diameter (65%, 53/81), tumours invading beyond the subserosa layer (78%, 46/59), and tumours with infiltrative growth (87%, 41/47). Furthermore, the frequency of Rd-type expression in cases with peritoneal dissemination (82%, 9/11) or lymph node metastasis (73%, 43/59) was significantly higher than that in cases without dissemination or metastasis. These results suggest that ECD might play a key role in the genesis of histological differentiation, and that the reduction of ECD expression may affect the mode of invasion and metastasis of human gastric cancer cells.

Adenocarcinoma↗
PubMed1992

Cadherin-mediated cell-cell adhesion is perturbed by v-src tyrosine phosphorylation in metastatic fibroblasts.

Rat 3Y1 cells acquire metastatic potential when transformed with v-src, and this potential is enhanced by double transformation with v-src and v-fos (Taniguchi, S., T. Kawano, T. Mitsudomi, G. Kimura, and T. Baba. 1986. Jpn. J. Cancer Res. 77:1193-1197). We compared the activity of cadherin cell adhesion molecules of normal 3Y1 cells with that of v-src transformed (SR3Y1) and v-src and v-fos double transformed (fosSR3Y1) 3Y1 cells. These cells expressed similar amounts of P-cadherin, and showed similar rates of cadherin-mediated aggregation under suspended conditions. However, the aggregates or colonies of these cells were morphologically distinct. Normal 3Y1 cells formed compacted aggregates in which cells are firmly connected with each other, whereas the transformed cells were more loosely associated, and could freely migrate out of the colonies. Overexpression of exogenous E-cadherin in these transformed cells had no significant effect on their adhesive properties. We then found that herbimycin A, a tyrosine kinase inhibitor, induced tighter cell-cell associations in the aggregates of the transformed cells. In contrast, vanadate, a tyrosine phosphatase inhibitor, inhibited the cadherin-mediated aggregation of SR3Y1 and fosSR3Y1 cells but had little effect on that of normal 3Y1 cells. These results suggest that v-src-mediated tyrosine phosphorylation perturbs cadherin function directly or indirectly, and the inhibition of tyrosine phosphorylation restores cadherin action to the normal state. We next studied tyrosine phosphorylation on cadherins and the cadherin-associated proteins, catenins. While similar amounts of catenins were expressed in all of these cells, the 98-kD catenin was strongly tyrosine phosphorylated only in SR3Y1 and fosSR3Y1 cells. Cadherins were also weakly tyrosine phosphorylated only in the transformed cells. The tyrosine phosphorylation of these proteins was enhanced by vanadate, and inhibited by herbimycin A. Thus, the tyrosine phosphorylation of the cadherin-catenin system itself might affect its function, causing instable cell-cell adhesion.

Animals↗
PubMed1989

Lymphomatoid papulosis: ultrastructural, immunohistochemical and gene analytical studies.

Ultrastructural, immunohistochemical and gene analytical studies were carried out on a 39-year-old patient with lymphomatoid papulosis. Two different cell groups were demonstrated in the papulonodular eruptions: large atypical cells with multiple nuclei that were well stained with anti-Tac, but not with Leu 3a, and other cells that possessed prominent hyperchromatic nuclei and which stained well with Leu I and Leu 3a but not with anti-Tac. Gene analytical studies using EcoRI, BamHI and HindIII revealed no rearrangement, indicating a non-clonal T-cell proliferation unlike malignant T-cell lymphoma. These results suggest that the present case was benign.

Adult↗
PubMedDate not supplied

Establishment and characterization of a novel in vitro angiogenesis model using a microvascular endothelial cell line, F-2C, cultured in chemically defined medium.

The behavior of vascular endothelial cells (EC) is an important factor in the processes involved in angiogenesis, but the regulatory mechanisms of angiogenesis, especially underlying the tubulogenesis by EC are not yet clear. Although a number of in vitro experimental models of tubulogenesis have been developed by use of cultured EC, most of those models are too complex to be easily handled and further, the culture media are usually supplemented with serum, creating problems in interpretation of experimental results. To generate a simple in vitro angiogenesis study model under serum-free culture conditions, we adapted a murine microvascular endothelial cell line, F-2, to a chemically defined medium, Cos Medium 001, and successfully established a subline of F-2, designated F-2C, which revealed a unique growth pattern. In Cos Medium 001, F-2C proliferates in a cobblestone pattern at an early growth stage, but, at a late growth stage, spontaneously differentiates to form three-dimensional honeycomblike tubular structures without the supplementation of any specific factors. The cell aggregation activity of F-2C in the presence of Ca2+ was much greater than that of F-2. The amount of subendothelial matrix deposited by F-2C was significantly higher than that by F-2, and increased prominently after the F-2C cells reached the differentiating stage of tubulogenesis. These findings indicate that F-2C is a new EC line in which tubulogenesis is spontaneously induced by the marked deposition of basement membrane analog to the subendothelial matrix and by the enhancement of presumable cadherin activity. We suggest that this cell line, F-2C, represents a simple and useful in vitro angiogenesis model.

Animals↗