Noriaki Toyota

Fibroepithelioma-like changes occurring in perianal Paget's disease with rectal mucinous carcinoma: case report and review of 49 cases of extramammary Paget's disease.

Background:  Anogenital Pagets disease (PD) may be accompanied by varying degrees of epidermal hyperplasia. The histological changes can be reminiscent of fibroepithelioma of Pinkus.

FK506 and cyclosporin A inhibit stem cell factor-dependent cell proliferation/survival, while inducing upregulation of c-kit expression in cells of the mast cell line MC/9

Abstract Murine mast cell proliferation and maturation are regulated by two distinct cytokines, interleukin-3 (IL-3) and the c-kit ligand, stem cell factor (SCF). In this study using cells of the mouse mast cell line, MC/9, the effects of two immunosuppressants, FK506 and cyclosporin A (CsA), were investigated. Withdrawal of IL-3 from the culture medium resulted in loss of viability of MC/9 cells. The addition of SCF in the absence of IL-3 maintained MC/9 cell survival but no cell proliferation was detected. The combined addition of IL-3 and SCF to the culture medium resulted in a more marked MC/9 cell proliferation than the addition of IL-3 alone. FK506 and CsA inhibited the SCF-dependent, but not the IL-3 dependent, stimulatory effects on MC/9 cell proliferation/survival. Apoptotic changes were analyzed using fluorescent staining with acridine orange and DNA electrophoresis. FK506 and CsA inhibited the SCF-dependent rescue effect from apoptosis. Flow cytometry showed that FK506 and CsA did not affect IL-3 receptor expression. However, immunoblot and reverse transcriptase-polymerase chain reaction (RT-PCR) analyses indicated that c-kit protein and c-kit mRNA transcripts were increased following the FK506 and CsA treatments in the presence of IL-3. In addition, MC/9 cells pretreated with FK506 or CsA showed an increased adhesiveness to NIH/3T3 cells that express membrane-bound SCF. Neither FK506 nor CsA affected c-kit tyrosine phosphorylation or MAP kinase nuclear translocation of MC/9 cells following SCF stimulation. These results indicate that FK506 and CsA, while inducing c-kit of MC/9 cells, selectively inhibit the SCF-dependent stimulatory effects on MC/9 cell proliferation/survival by a mechanism independent of, or at point(s) distal to, the c-kit-MAP kinase pathway.

Transforming growth factor β1 inhibits IL-3- and IL-4-dependent mouse connective tissue-type mast cell proliferation

Transforming growth factor Β1 (TGFΒ1) is a regulator of cell proliferation and differentiation. Using a mouse peritoneal cell-derived mast cell culture system, we investigated the effects of TGFΒ1 on mast cell proliferation. TGFΒ1 inhibited IL-3- and IL-4-dependent connective tissue-type mast cell proliferation. The effect was concentration dependent: 50% inhibition was observed with 1.0 ng/ml TGFΒ1 and the maximal inhibitory effect (no proliferation), was observed with 10 ng/ml. Flow cytometric analysis suggested that the inhibitory effect of TGFΒ1 was due to blocking of both G1 and G2 phases. Both control and TGFΒ1-treated mast cells showed similar histamine release induced by the calcium ionophore, A23187. TGFΒ1 seems to be an important negative regulator of connective tissue-type mast cell proliferation with apparently no appreciable effect on mast cell function.

A Case of Skin Metastasis from Follicular Thyroid Carcinoma

We present a case of skin metastasis from follicular thyroid carcinoma which developed on the scalp of a 72-year-old man. The lesion was noticed 1 month after a surgical excision of the primary thyroid carcinoma and gradually enlarged during the past 11 months. A biopsy from the nodule showed mostly well-differentiated thyroid follicular structures with colloid material. Tumor cells showed mild variation of nuclear size and shape in almost all areas. We performed immunohistochemistry using antithyroglobulin antibody, which established the diagnosis of a metastatic lesion from thyroid follicular carcinoma. Total thyroidectomy and 131I radiotherapy were performed. No further metastasis has been discovered during the last 18 months.

Inhibitory effect of 1α,25-dihydroxyvitamin D3 on mast cell proliferation and A23187-induced histamine release, also accompanied by a decreased c-kit receptor

Using mouse peritoneal mast cells, we investigated the effects of 1α,25-dihydroxyvitamin D3 (calcitriol) on mast cell proliferation and histamine release. Calcitriol did not affect IL-3/IL-4-dependent mast cell proliferation, but it selectively inhibited stem cell factor-dependent mast cell proliferation and colony formation. Immunohistochemical and immunoblot analyses revealed that calcitriol treatment reduced expression of purified peritoneal mast cell c-kit protein. Using a mast cell line, MC/9, both c-kit protein and c-kit mRNA transcript were seen to be reduced following calcitriol treatment. Calcitriol also reduced histamine release induced by calcium ionophore A23187. In contrast, anti-IgE antibody-dependent histamine release was not affected by calcitriol. Our results indicate that calcitriol inhibits mast cell proliferation and A23187-induced histamine release that might be associated with a decreased expression of c-kit receptor.

Glucocorticoids inhibit proliferation and adhesion of the IL-3-dependent mast cell line, MC/9, to NIH/3T3 fibroblasts, with an accompanying decrease in IL-3 receptor expression

Abstract We investigated the effects of glucocorticoids on IL-3-dependent proliferation and c-kit expression of cells of the mouse mast cell line, MC/9. Glucocorticoids (dexamethasone, prednisolone, and hydrocortisone) inhibited IL-3-dependent MC/9 cell proliferation, whereas sex steroids (progesterone, β-estradiol, and testosterone) had no effect. Flow cytometric analysis revealed that glucocorticoids reduced the expression of the IL-3 receptor on MC/9 cells. Immunoblot and Northern blot analyses indicated that glucocorticoids also reduced the expression of both c-kit protein and c-kit mRNA transcript. Furthermore, the adhesion of MC/9 cells to stem cell factor-expressing NIH/3T3 cells was reduced following glucocorticoid treatment. Our results indicate that glucocorticoids inhibit IL-3-dependent MC/9 mast cell proliferation, with an accompanying decrease in IL-3 receptor expression. Glucocorticoids also reduced c-kit expression on MC/9 cells resulting in a decreased adhesion to NIH/3T3 fibroblasts.

Effects of FK506 and Cyclosporin a on proliferation, histamine release and phenotype of murine mast cells

Using mouse peritoneal cavity mast cells, we investigated the effects of FK506 and cyclosporin A (CsA) on cell proliferation and histamine release induced by anti-IgE antibody, calcium ionophore (A23187), or neuropeptide (substance P). Both FK506 and CsA inhibited cytokine-dependent mast cell proliferation in a dose-dependent manner. The inhibitory effects of these compounds on mast cell proliferation was reversible; the removal of the chemicals from the incubation medium resulted in the reinitiation of mast cell proliferation. Flow cytometric analysis suggested that the inhibitory effect of FK506 and CsA was mostly due to G1/S boundary block, although a significant number of G2-arrested cells were also observed following FK506 treatment. Both FK506- and CsA-treated mast cells showed a similar inhibition of histamine release induced by A23187. However, CsA at higher concentrations inhibited the histamine release induced by anti-IgE antibody or substance P more markedly than FK506. Cellular histamine content was decreased by CsA treatment while FK506 had no effect. The staining properties of peritoneal mast cells changed from connective tissue-type mast cell-like to mucosal mast cell-like during CsA treatment but not during FK506 treatment. Thus FK506 and CsA have different effects on mast cell proliferation as well as histamine release, that might be associated with a phenotypic change of the cells during culture.

Immunohistochemical Differential Diagnosis between Lymphocytoma Cutis and Malignant Lymphoma in Paraffin-embedded Sections

A panel of monoclonal antibodies (Leucocyte Common Antigen [CD45], LN‐1 [CDw75], LN‐2 [CD74], LN‐3, L‐26, UCHL‐1 [CD45RO] and MT‐1) which identify B and T cell surface markers were applied to benign lymphocytoma cutis and malignant lymphoma of the skin in paraffin‐embedded sections.