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Biomedical subjects

M Furue

Publications and source records attributed to M Furue.

At least 145 records · Page 8Linked to original sources
PubMed1992

Epitope mapping of CD1a, CD1b, and CD1c antigens in human skin: differential localization on Langerhans cells, keratinocytes, and basement membrane zone.

CD1 antigens are classified into at least three groups, CD1a, CD1b, and CD1c. In order to delineate the localization of epitopes of CD1 antigens in human skin, we examined the immunoreactivity of fourteen different CD1 antibodies (seven CD1a, five CD1b, and two CD1c antibodies). The epitopes for CD1a, CD1b, and CD1c are differentially localized on epidermal Langerhans cells, dermal dendritic cells, keratinocytes, the luminal portion of eccrine gland ducts, and the basement membrane zone in normal human skin.

Antibodies↗
PubMed1992

Simple epithelial cytokeratin-expression in seborrheic keratosis.

The cytokeratin expression of seborrheic keratosis was studied by means of immunohistochemistry and compared with that of normal human skin. The following findings were obtained in seborrheic keratosis: (1) a partial lack of high molecular weight cytokeratin (#1/68 kD, #10/56.6 kD) in all ten cases examined; (2) the detection of cytokeratin typical for simple epithelia (#8/52.5 kD, #18/45 kD, #19/40 kD) in eight of ten cases; and (3) the detection of cytokeratin #5/58 kD in suprabasal cells in 5 of 10 cases. An immunoelectron-microscopic investigation, using an anti-keratin antibody against cytokeratin #19/40 kD, revealed a whirl-like arrangement of keratin filaments within immunoreactive cells, in contrast to a linear, parallel arrangement in non-immunoreactive cells. Cells known to express cytokeratin typical for simple epithelia, such as sweat gland cells or Merkel cells, were not observed. The altered cytokeratin gene-expression in seborrheic keratosis may be attributable to de-differentiation of tumor cells or potential re-differentiation towards embryonic keratinocytes.

Adult↗
PubMed1991

Differential regulation by dexamethasone and cyclosporine of human T cells activated by various stimuli.

Calcium ionophores such as ionomycin (IONO), CD3 antibody (CD3), or CD28 antibody (CD28) have been shown to stimulate T cells in a quite different fashion. However, each stimulator induces full activation of resting T cells in the presence of phorbol myristate acetate. Human T cells were activated with PMA + CD3, PMA + IONO, or PMA + CD28 and the inhibitory effects of dexamethasone (DEX) and cyclosporine were examined on [3H]-TdR incorporation, IL-2 production, and IL-2 receptor expression. Three inhibition patterns emerged: PMA + CD3 stimulation was DEX-sensitive and CsA-sensitive, PMA + IONO stimulation was CsA-sensitive but DEX-resistant, PMA + CD28 stimulation was DEX-sensitive but CsA-resistant. Although the degree of inhibition by DEX and CsA was different in [3H] TdR incorporation, IL-2 production, and IL-2 receptor expression assays, the inhibitory pattern of these drugs was similar in each of the assays, indicating that human T cell activation is differentially regulated by DEX and CsA depending on the stimulator.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1991

Responsiveness to interleukin 4 and interleukin 2 of peripheral blood mononuclear cells in atopic dermatitis.

Although the pathogenesis of atopic dermatitis (AD) is unknown, many immunologic abnormalities such as high levels of serum IgE and increase of IgE Fc receptor-positive lymphocytes have been demonstrated. Recently, interleukin 4 (IL-4) has been shown to induce enormously the production of IgE and to enhance the expression of IgE Fc receptor by B cells, suggesting the possible involvement of IL-4 in the pathogenesis of AD. We examined IL-4 responsiveness or interleukin 2 (IL-2) responsiveness of peripheral blood mononuclear cells of 31 patients with AD, 19 healthy individuals, and seven patients with other skin diseases. We found that IL-4 responsiveness of AD was higher than that of non-AD control, although IL-2 responsiveness of AD showed no significant change. However, the value of the IL-4 responsiveness did not significantly correlate with the clinical severity, personal history of respiratory allergy, serum IgE level, or clinical course of patients with AD. The hyperresponsiveness to IL-4 detected in AD was not likely to be due to the effects of steroids or anti-mast cell drugs because the value of IL-4 responsiveness was significantly low, compared to AD, in patients with other skin diseases who were treated similarly. Because the T-cell-enriched population, but not the B-cell-enriched population, showed significant proliferation in response to exogenous IL-4 or IL-2, T cells were the main population that reacted in our proliferation assay. These results indicate that IL-4-driven proliferative response may be efficiently operative in T cells in patients with AD.

B-Lymphocytes↗
PubMed1991

Gangliosides inhibit the proliferation of human T cells stimulated with interleukin-4 or interleukin-2.

T cell growth factors such as interleukin-2 (IL-2) and interleukin-4 (IL-4) act as potent comitogenic factors for purified human T cells in the presence of phorbol myristate acetate (PMA). We investigated the effects of gangliosides on the IL-4-driven or IL-2-driven proliferation of human T cells, using these comitogenic assays. Bovine brain gangliosides inhibited the proliferation of human T cells activated by PMA + IL-4 or PMA + IL-2. These inhibitory effects were dose and time-dependent and were significant at concentrations higher than 50 microM. PMA + IL-2 stimulation was more sensitive to the inhibitory effects of gangliosides (I50 = 77.2 microM) than PMA + IL-4 stimulation (I50 = 105.9 microM). Differential inhibitory effects were also examined among the panel of various gangliosides. GD1b and GT1b showed the most potent inhibitory actions in each assay; the inhibitory effect of GD1a was somewhat less potent than GD1b or GT1b. GM2 and GD3 were only weakly inhibitory, and the inhibitory effect of GM3 was almost negligible. These findings suggest that gangliosides may play an immunomodulatory role by interfering with IL-4 or IL-2-driven proliferation of human T cells.

Dose-Response Relationship, Drug↗
PubMed1991

Phenotypic analysis of CD23+ peripheral blood mononuclear cells in atopic dermatitis.

There is an increase in the number of CD23+ cells in peripheral blood mononuclear cells (PBMC) in atopic dermatitis (AD). We analysed the subpopulation of CD23+ PBMC in 11 patients with AD and in 10 healthy controls and found that B cells (CD20+) and non-T, non-B cells (CD3- CD20-) (mainly monocytes) were responsible for the elevation of CD23+ cells. CD23+ T cells (CD3+) comprised only 4.6% of total CD23+ cells in AD. The percentage of CD23+ cells did not correlate with the serum log IgE level nor with clinical severity of AD. Interleukin 4 (IL-4) induced the expression of CD23 antigen in PBMC both in AD and in healthy controls in a dose-dependent manner in vitro. This enhancing effect of IL-4 was completely abrogated by the addition of anti-IL-4 monoclonal antibody. Other cytokines such as IL-1, IL-2, IL-3, IFN-alpha, IFN-gamma and TNF-alpha had no significant effects on CD23 expression.

Adolescent↗
PubMed1990

Coordinate expression of src family protooncogenes in T cell activation and its modulation by cyclosporine.

Activation of T lymphocytes induces transcription of several important genes which encode lymphokines and lymphokine receptors as well as "proliferation complementary" protooncogenes like c-myc or c-fos. Recently, the expression of lck gene, one of the src family gene, has also been shown to be modulated during T cell activation. We, therefore, assessed the question of whether other src family genes are expressed during the activation of T cells and of whether cyclosporine, a potent immunosuppressive drug, affects expression of these genes. We examined the expression of four different src family genes (lck, c-src, fyn, and c-fgr) in addition to the expression of IL-2, c-fos, c-myc, and actin genes in murine T cells which were activated with PMA plus ionomycin or PMA plus anti-CD3 mAb. We found that T cell activation was associated with the up-regulation of these src family genes and that the expression of these genes was specifically blocked in the presence of cyclosporine indicating that these activation-related genes were coordinately regulated.

Blotting, Northern↗
PubMed1990

Differential inhibition of the T cell activation pathway by dexamethasone and cyclosporine.

We examined the inhibitory capacity of dexamethasone (DEX) and cyclosporine (CsA) on T cell activation using various accessory cell (AC)-dependent and AC-independent stimuli. We found that CsA strongly inhibited T cell activation in each of the assays used: allogeneic T cell stimulation, phorbol myristate acetate plus concanavalin A, PMA plus anti-CD3 monoclonal antibody (2C11), or PMA plus ionomycin (IONO) T cell activation. DEX was a potent inhibitor of allogeneic stimulation and of the PMA+Con A- or PMA + 2C11-induced T cell stimulation. PMA + IONO stimulation, however, was not affected by DEX. When inhibition occurred, both drugs suppressed [3H]TdR incorporation, IL-2 production, and IL-2 mRNA accumulation, indicating that the sites of interference of these drugs in the T cell activation pathway are located proximal to IL-2 mRNA accumulation. However, the difference in the effects of DEX and CsA in PMA + IONO stimulation suggests that DEX and CsA differentially affect T cell activation.

Animals↗
PubMed1989

Direct effects of glucocorticosteroids on epidermal Langerhans cells.

To determine the direct effects of glucocorticosteroids on epidermal Langerhans cells (LC), we treated isolated LC with dexamethasone (DEX) in vitro, and investigated Ia expression by LC using immunofluorescence microscopy and FACS analysis. We found that DEX directly decreased the number of Ia+ LC in a dose- and time-dependent manner. Pulse incubation with DEX also inhibited the immunostimulatory function of LC in vitro. FACS analysis demonstrated that LC detected in DEX-treated culture expressed a similar amount of Ia antigen and Fc receptor on the cell surface as LC cultured with the solvent control, suggesting that LC may be composed of a heterogeneous population in terms of sensitivity to DEX, and DEX may completely abolish the expression of surface molecules on a subpopulation of LC or may be cytolytic to this sensitive population.

Animals↗
PubMed1989

Hyperresponsibility to exogeneous interleukin 4 in atopic dermatitis.

Many humoral and cellular immunological abnormalities have been reported in atopic dermatitis (AD). Since interleukin 4 (IL-4) enhances IgE production and IgE-Fc receptor expression by B cells as well as [3H]-TdR incorporation by T cells, we hypothesized that IL-4 may play an important role in the regulation of the immune response in AD. We examined [3H]-TdR incorporation by peripheral blood lymphocytes from AD patients or from non-AD controls in the presence or absence of IL-4 or interleukin 2 (IL-2). We found that IL-4/IL-2 responsiveness was significantly higher in AD than controls, although the IgE levels did not seem to be correlated with IL-4/IL-2 responsiveness. It is possible that most humoral and cellular immunological abnormalities of AD may be due to this hyperresponsibility to IL-4.

Adolescent↗
PubMed1989

[Cellular immunoregulation in atopic dermatitis--hyperresponsiveness to interleukin-4 and hyporesponsiveness to interleukin-2].

We examined the responsiveness to Interleukin-4 (IL-4) and Interleukin-2 (IL-2) of peripheral blood lymphocytes from patients with atopic dermatitis (AD) and non-AD controls. The IL-4 responsiveness of the AD patients was found to be higher than that of the non-AD controls. In contrast, the IL-2 responsiveness of the AD patients was relatively lower than that of the non-AD controls. When IL-4/IL-2 responsiveness ratio was compared, the IL-4/IL-2 responsiveness ratio of the AD patients (54.1 +/- 18.5) was significantly higher than that of the non-AD controls (24.8 +/- 9.9, p less than 0.001). The high IL-4/IL-2 responsiveness ratio found in the AD patients may possibly be related to the pathogenesis of AD.

Adolescent↗
PubMed1989

Identification of fyn-encoded proteins in normal human blood cells.

We have previously reported that carboxyl terminal truncations of the normal human fyn gene, a member of the src subfamily, can transform immortal mouse fibroblasts to full malignancy. In search of evidence which suggests the possible activation of the human fyn gene, we have screened DNAs and RNAs from a number of human tumor cell lines. The results indicate that the fyn gene is not frequently changed grossly in the naturally occurring tumors. To establish a basis for understanding the physiological function(s) of this highly conserved gene, we have prepared specific antibodies to the fyn-encoded proteins. Using them we have shown the presence of fyn proteins in human lymphocytes and monocytes and their protein-tyrosine kinase activity.

Blood Cells↗
PubMed1988

The effect of cyclosporine on epidermal cells. I. Cyclosporine inhibits accessory cell functions of epidermal Langerhans cells in vitro.

Although the precise mechanism of action of cyclosporine (CS) is unknown, there is substantial evidence that CS preferentially acts on T cells by impairing lymphokine production. Recent studies have demonstrated that CS may also inhibit the functions of accessory cells and APC. Since topically applied CS inhibits contact sensitivity and epidermal Langerhans cells (LC) are very effective accessory cells and APC, we determined whether CS directly affects their accessory cell functions. Murine LC were pulsed with solvent control or with various doses of CS (up to 10 micrograms/ml) and then Con A-induced T cell proliferation was assayed. CS pulsing of LC caused, when compared with solvent control-pulsed LC, a dose-dependent decrease in T cell stimulation (up to 93%). LC fixed with paraformaldehyde after 2-h CS pulsing showed a similar degree of decreased accessory cell function, indicating that the immunosuppressive action is established by 2 h. The inhibitory capacity of CS pulsing on LC is not likely to be related to diminished IL-1 production, enhanced PG biosynthesis, or decreased surface Ia Ag intensity. The possibility of carryover of CS into the culture supernatants was ruled out by adding CS-pulsed LC or their supernatants to other T cell proliferative assays. Thus, these studies indicate that CS directly inhibits accessory cell functions of LC.

Animals↗
PubMed1988

Molecules on activated human T-cells.

Recent technical advances in immunology (such as the development of monoclonal antibodies, FACS analysis, molecular biology techniques, etc.) have enormously expanded our understanding of the process of T-cell activation. In this paper, we review some of the characteristics of surface molecules of activated human T-cells.

Antibodies, Monoclonal↗