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Biomedical subjects

I Katayama

Publications and source records attributed to I Katayama.

At least 91 records · Page 5Linked to original sources

Epidermal cytokine mRNA expression induced by hapten differs from that induced by primary irritant in human skin organ culture system.

Epidermal cells produce various kinds of cytokines and express cell adhesion molecules. To analyze early events which induced in human epidermis by stimulation with various chemicals, we analyzed mRNA of cytokines expressed in epidermis in a human skin organ culture system. After painting haptens, primary irritants or vehicle control on human skin specimens sliced to 1 mm thickness and cut into approximately 5 x 5 mm blocks, the pieces were cultured in serum-free medium. After separating epidermis from dermis, total RNA was extracted and mRNA of cytokines was assessed by the reverse transcriptase-poly-merase chain reaction. Only haptens induced IL-1 beta mRNA at 1-3 hours. TNF-alpha mRNA was induced 9 hours after application of haptens and 1 hour after application of primary irritants. IL-1 alpha mRNA was not induced by either haptens or primary irritants. Thus, cytokine mRNA expression induced by haptens in epidermis differs from that induced by primary irritants.

Acetone↗

Necrobiosis lipoidica-like skin lesions in systemic sarcoidosis.

A 62-year-old woman with systemic sarcoidosis developed erythematous plaques on her lower legs. Clinically, two kinds of skin lesions were distinguished; one type formed brownish-red plaques with induration suggesting plaque-type skin sarcoid, and the other formed purplish erythematous plaques with atrophic centers resembling necrobiosis lipoidica. In spite of this clinical appearance, a biopsy specimen from one of the latter lesions revealed typical skin sarcoid histology composed of discrete non-caseating granulomas, while that from one of the other lesions showed necrobiotic changes of collagen bundles surrounded by epitheloid histiocytes and foreign-body giant cells. Because cutaneous involvement of sarcoidosis may mimic necrobiosis lipoidica clinically and/or histologically, we diagnosed her skin lesions as necrobiosis-like skin sarcoid.

Collagen↗

TNF-alpha, RANTES, and MCP-1 are major chemoattractants of murine Langerhans cells to the regional lymph nodes.

We have previously reported that lymph node cells generated chemotactic factors for Langerhans cells (LCs) in the induction phase of contact dermatitis. In order to clarify the chemotactic factors involved in migration to the regional lymph nodes, we investigated the migratory activity of murine LCs toward several cytokines and chemokines in vitro. One-day cultured LC-enriched epidermal cells were added to the upper compartment of a modified Boyden chamber and cytokines were added to the lower compartment. We counted dendritic cells migrated to the lower chamber as LCs under phase contrast microscopy. About 99% of migrated dendritic cells were positively reacted with anti-Ia(d) and NLDC145 antibodies and considered to be LCs. We could detect LC migration more accurately by this direct examination than by counting the migrated cells in the filter membrane of a Boyden chamber. In our system, migration of murine epidermal LCs was stimulated by TNF-alpha, RANTES and MCP-1, but not by GM-CSF, IL-1beta, IL-4, and IL-6. TNF-alpha induced LC migration at concentrations from 4 x 10(3) U/ml to 5 x 10(4) U/ml. RANTES at concentrations from 10 to 100 ng/ml and MCP-1 at a concentration of 100 ng/ml induced LC migration in a dose-dependent manner. These data confirmed that TNF-alpha, RANTES, and MCP-1 induced LC migration from epidermis during contact sensitization.

Animals↗

Alteration of cytokine genes and bcl-2 expression following immunotherapy with intralesional IFN-gamma in a patient with tumor-stage mycosis fungoides.

BACKGROUND: Interferon-gamma (IFN-gamma) is used in the treatment of tumor stage mycosis fungoides (MF), whereas its mechanism is still unknown. We have previously shown that treatment with intralesional IFN-gamma induced tumor regression. OBJECTIVE: To explore the possibility that IFN-gamma may alter the cytokine expression by tumor cells, we studied cytokine gene expression in a tumor nodule of MF. METHODS: By using the reverse transcriptase-polymerase chain reaction, Th1- and Th2-type cytokine mRNA expression was examined before and after intralesional IFN-gamma therapy. Additionally, we examined bel-2 protein expression on tumor cells. RESULTS: We found weak mRNA expression of interleukin-4 (IL-4) and IL-5, and strong expression of IL-6, IL-10 and IFN-gamma before therapy. After successful treatment of intralesional IFN-gamma, mRNA expression of IL-5, IL-6 and IL-10 were significantly reduced and IL-2 mRNA was mildly induced. Culture for 24 h of tumor cells with IFN-gamma showed upregulation of IL-2 mRNA and downregulation of IL-6 mRNA expression. bcl-2 expression was significantly decreased after successful intralesional IFN-gamma therapy, photochemotherapy (PUVA) and radiation therapy. CONCLUSION: These data suggest that IFN-gamma induces tumor regression by affecting cytokine gene expression in MF tumor lesions. The reduced bcl-2 expression did not seem to be induced by a direct immunological affect of IFN-gamma, but to represent a nonspecific result of tumor regression after successful treatment.

Cytokines↗

Expression of stem cell factor in the lesional skin of systemic sclerosis.

BACKGROUND AND OBJECTIVE: Mast cells are thought to play an important role in the pathogenesis of systemic sclerosis (SSc), although their significance is still unknown. As mast cells are increased in number in the lesional skin of the early stage of scleroderma, we addressed the question whether expression of stem cell factor (SCF), a mast cell growth factor, is upregulated in the lesional skin. METHODS: Immunohistochemical analysis of SCF was performed in paraffin-embedded skin sections from the lesions of 18 patients with SSc (13 in the edematous and 5 in the sclerotic phase) and from normal skin of 5 subjects. SCF messenger RNA expression was also examined on cultured fibroblasts derived from SSc by using reverse-transcriptase polymerase chain reaction. RESULTS: Immunostaining showed focal expression for SCF in fibroblast-like spindle-shaped cells, mast cells, keratinocytes and endothelial cells. SCF-positive spindle-shaped cells were significantly increased in the reticular dermis in the early edematous stage of SSc (33.7 +/- 13.0/mm2) as compared with normal skin (18.3 +/- 4. 2/mm2; p <0.05); however, there was no significant difference between the sclerotic phase (18.9 +/- 6.9/mm2) and normal skin. mRNA expression of SCF was detected both in cultured scleroderma-derived and normal skin-derived fibroblasts. CONCLUSION: These results may suggest that SCF plays a role in the fibrotic process in early-stage SSc.

Adult↗

Experimental study for the development of an in vitro test for contact allergens. 2. Comparison of the in vitro sensitization test with the guinea pig maximization test for contact allergens.

We have previously reported an in vitro hapten-specific sensitization method using Pam-212 cells (in vitro sensitization test) to identify the potential effectiveness of contact allergens. In the present study, we conducted comparison studies of 11 allergens and 2 irritants in order to evaluate the method as an alternative predictive test. The guinea pig maximization test (GPMT) was developed based on the test described by Magnusson and Kligman. Our assay was carried out as follows: we treated Pam-212 cells with 13 test chemical solutions, while T cells and macrophages of BALB/c mice were cultured with hapten-conjugated Pam-212 cells for 5 days. After incubation, 10(5) T cells were stimulated with mitomycin-C-treated spleen cells conjugated with chemicals. Three days later, the [3H]methyl thymidine incorporation was counted. The results of the GPMT were in agreement with those reported in previous studies except for benzocaine. In our GPMT experiments, benzocaine was negative, but it had been classified as a moderate sensitizer in previous studies. Our assay detected extreme, strong and moderate sensitizers as previously classified by the GPMT They could be summarized as follows: three of five chemicals classified as moderate sensitizers, and 100% of strong or extreme sensitizers were detected by both the GPMT and the in vitro sensitization test. No irritants showed a positive reaction in our assay. These results support the view that the sensitivity of our in vitro test may be equivalent to that of the GPMT and may be useful as a rapid and objective allergen screening test.

Allergens↗

Nitric oxide production and inducible nitric oxide synthase expression in systemic sclerosis.

OBJECTIVE: We examined whether serum levels of nitric oxide (NO) are elevated in patients with systemic sclerosis (SSc). METHODS: The concentration of NO was determined by Griess reagents. Immunohistochemical studies were also performed to examine inducible NO synthase (iNOS) protein expression in specimens of lesional skin of SSc. Messenger RNA (mRNA) expression of iNOS was examined by reverse transcriptase-polymerase chain reaction. RESULTS: The mean serum concentrations of NO were significantly higher in patients with SSc (47.8 +/- 17.0 microM) (mean +/- SD) compared with controls (25.6 +/- 10.3 microM). Immunohistochemical studies showed that iNOS was expressed on infiltrating mononuclear cells, endothelial cells, and fibroblasts in the lesional skin of SSc, while in normal skin iNOS protein was negative on fibroblasts. iNOS gene expression was detected on cultured fibroblasts derived from SSc skin, but not on cultured fibroblasts from normal skin. CONCLUSION: Our results suggest that increased NO levels may contribute to the abnormal regulation of fibroblasts in the fibrotic process in SSc.

Adult↗

Analysis of T cell receptor Vbeta repertoires of annular erythema associated with Sjögren's syndrome.

Sjögren's syndrome (SjS) is an autoimmune disorder characterized by lymphocytic infiltration into the lacrimal and salivary glands. Annular erythema has recently been reported to be a specific, cutaneous manifestation associated with SjS. In this study, the T cell receptor (TCR) Vbeta gene usage and expansion was examined in annular erythema associated with SjS (AESjS) in 7 patients with primary SjS (5 definite and 2 probable), using reverse transcriptase polymerase chain reaction (RT-PCR) amplification of 22 Vbeta gene families. For 4 out of the 7 patients, the TCR V repertoire in lesional skin of AESjS was compared with paired peripheral blood mononuclear cells (PBL). In one case, two lesional tissue specimens biopsied from different sites of AESjS (face and trunk) were examined. As a control, the TCR Vbeta repertoire was examined from the lesional skin of butterfly rash biopsied from 3 cases of systemic lupus erythematosus (SLE). Results showed that TCR Vbeta 2 was detected in 6 out of the 7 cases of AESjS, although diverse usage was observed. TCR Vbeta 2 and 17 (but particularly Vbeta 2) were predominantly expressed in AESjS in comparison with paired PBL. In the case which presented AESjS at two separate sites, Vbeta 2, 6, 18 and 19 were preferentially expressed in both skin sites as compared with PBL. On the other hand, TCR Vbeta 6, 13-2 and 14 were commonly demonstrated in the cutaneous lesions of SLE. These results suggest that (1) the TCR Vbeta usage by infiltrating T cells in AESjS is not strictly limited, however, Vbeta 2 may play an important role in the induction of AESjS, and that (2) different subsets of TCR Vbeta genes are used in the lesional skin of SjS and SLE, which might account for the clinical and histological differences seen in the erythema found in these two autoimmune disorders.

Adolescent↗

Cyclophosphamide-induced blood and tissue eosinophilia in contact sensitivity: mechanism of hapten-induced eosinophil recruitment into the skin.

The mechanism leading to selective production and accumulation of eosinophils in certain allergic skin diseases is unknown. Cyclophosphamide treatment (150 mg/kg) of BALB/c mice 48 h before sensitization with picryl chloride (PCl) resulted in striking blood and tissue eosinophilia, maximal at 13 days. Blood eosinophilia was not induced by the sensitization with oxazolone and 2,4-dinitrofluorobenzene. Challenge with 1 % PCl, but not croton oil caused preferential eosinophil accumulation into the dermis, which was associated with the enhanced expression of vascular cell adhesion molecule 1 (VCAM-1) on endothelial cells. Intravenous administration of anti-VCAM-1 monoclonal antibody abrogated eosinophil infiltration. In this murine model, we examined the role of several cytokines, including chemokines in inducing selective tissue eosinophilia in vivo. Local administration of antibodies against interleukin (IL)-1beta, IL-4, tumor necrosis factor (TNF)-alpha, and RANTES, but not against IL-5 before challenge inhibited hapten-induced eosinophil recruitment. Intradermal injection of recombinant (r)IL-1beta, rIL-4, rTNF-alpha, rRANTES, and rMIP-1alpha induced marked eosinophil accumulation. Nonetheless, intradermal rIL-5 was not a chemoattractant for eosinophils in vivo. Our findings suggest that IL-1beta, IL-4, TNF-alpha, and RANTES contribute to the selective accumulation of eosinophils in contact sensitivity reaction. Although circulating IL-5 can activate eosinophils and prolong their survival, locally secreted IL-5 is not crucial for inducing eosinophil recruitment into the skin.

Animals↗

Role of apoptosis in spontaneous regression of peripheral T-cell lymphoma arising in the skin or subcutis.

Apoptosis was suspected to play a significant role in spontaneous regression of skin lesions in four cases of peripheral T-cell lymphoma arising in the skin or subcutis. All of the patients had skin tumors with ulcer formation, but no metastasis to the lymph nodes or viscera. Biopsy showed a sea of CD3-positive lymphoma cells involving the dermis to the subcutis with scattered foci of coagulative necrosis. In the zone of incipient necrosis surrounding the core of coagulative necrosis, frequent apoptotic bodies were identified by electron microscopy (EM), and DNA strand breaks were detected in 34% to 51% (mean, 42%) of lymphoma cells by the TdT-mediated deoxyuridine triphosphate (dUTP)-biotin nick end-labeling (TUNEL). As for the pathogenesis of coagulative necrosis, ischemic necrosis attributable to lymphocytic vasculitis appeared unlikely, because necrotic foci were devoid of neutrophils and had no relation to vascular distribution. Primary cataclysmic apoptosis appeared more likely, but its pathogenetic role could not be established, because EM and TUNEL could not be applied to the core of the debris-ridden coagulative necrosis. Although these cases had been classified as pseudolymphomas because they were histologically malignant but clinically benign, they were in fact true lymphomas characterized by extensive coagulative necrosis with a high rate of apoptosis demonstrable in the zone of incipient necrosis.

Adolescent↗

Evaluation of non-steroidal ointment therapy for adult type atopic dermatitis: inquiry analysis on clinical effect.

Clinical analysis was performed on non-steroidal ointment therapy for 70 patients with refractory adult-type atopic dermatitis by the clinical data and patient's own evaluation of the therapy obtained through enquiries after discharge from the hospital. Forty cases (57%) were between 20 and 30 years old and the male and female ratio was 39/31. The clinical evaluations were subdivided into five groups; conditions worsened (n = 9), no-change (n = 9), slightly improved (n = 14), much improved (n = 29) and cured (n = 9). Although statistically not significant, the age of onset of atopic dermatitis and the start of use of steroid ointment was much higher while the duration of the atopic dermatitis was much shorter in the remission patients. The duration of steroid ointment therapy for the facial skin was significantly shorter in the remission group when compared to groups with worsened symptoms and no-change in symptoms. Family history and complications of atopic diseases, laboratory data including IgE titer, eosinophils and RAST score were not statistically significant in any group except for a higher prevalence of IgE antibodies against inhalant and food allergens in the group with worsened symptoms. Most patients still used steroid ointment on the trunk lesions while they ceased using from the topical steroid on the facial lesions after discharge. Most frequent precipitating factors pointed out by the patients were emotional stress, irritation by sweat or UV light and longstanding use of steroid ointment. Complications of cataracta and retinopathy were found in 12 cases. These results suggest that remission of adult-type refractory atopic dermatitis can be achieved by the combination of careful daily skin care, use of non-steroidal topical ointment and minimizing the precipitating factors.

Adolescent↗

Substance P augments fibrogenic cytokine-induced fibroblast proliferation: possible involvement of neuropeptide in tissue fibrosis.

Sodium-butyrate-pretreated and Con A-stimulated P815 mast cell line generated 3T3 fibroblast proliferating activity. This fibroblast stimulatory activity was partially abrogated by three different substance P antagonists such as spantide (NK1 antagonist), FK224 (NK1 and NK2 antagonist) or FK888 (NK1 antagonist) or anti-substance P antibody. In addition to P815 mastocytoma cell, IL3-dependent, bone marrow-derived mast cells also generated fibroblast proliferating activity which was also partially abrogated by substance P antagonists. Anti-fibrogenic cytokine antibodies also inhibited mast cell-derived fibroblast proliferating activity. Substance P or histamine augmented fibrogenic cytokine-induced fibroblast proliferation which indicates that mast cell-derived histamine or substance P play an important role in induction of tissue fibrosis in fibrosing diseases.

3T3 Cells↗

Topical glucocorticoid augments IgE-mediated passive cutaneous anaphylaxis in Balb/C mice and mast cell deficient WBB6F1 v/v mice.

BACKGROUND: In a last decade, new types of skin manifestations have been recognized in atopic dermatitis especially in Japan. They are frequently observed in adult patients with atopic dermatitis after a long-standing steroid ointment and termed adult type-atopic dermatitis. OBJECTIVE: To clarify whether topical glucocorticoid (GC) modulates cutaneous inflammatory reactions in addition to known anti-inflammatory effect, we have examined the effect of long-term application of topical GC on IgE-mediated murine cutaneous reactions. METHODS: Fifty microlitres of diflucortolone valerate (1 mg/mL), prednisolone valerateacetate (3 mg/mL), or triamcinolone acetonide (1 mg/mL) were applied seven times on alternate day, to the flank skin of mice. On day 12 when mice received the seventh application of GC, each mouse was given an intravenous application of IgE anti-DNP antibody (PCA titre > x 2560) 1 h before the skin test with 0.15% DNFB in acetone:olive oil (4:1) on the right pinna. The left pinna was painted with a vehicle as a control. Increased ear thickness was measured at 1, 4, 24, 48 and 72 h to assess the augmentry effect of GC. RESULTS: Topical application of GC (50 microg diflucortolone valerate in ethanol) on the flank skin seven times on alternate days, augmented expression of passive cutaneous anaphylaxis reaction on the ear skin induced by intravenous applications of monoclonal IgE anti-DNP antibody and following the challenge test. In contrast, topical application of GC inhibited the reactions when applied on the challenged sites. Several types of GC, but not vitamin D3, augmented the skin reactions and these augmented reactions persisted for 72 h when control skin reactions subsided. GC induced a late phase but not an early phase cutaneous reaction in mast cell deficient WBB6F1 v/v mice by IgE anti-DNP antibody. CONCLUSION: Long-term application of topical GC might modulate local cutaneous immune response and augment IgE-mediated cutaneous reactions. Fc epsilon R(+) cells other than mast cell might be involved in the IgE-mediated late-phase reaction.

Administration, Topical↗

The inhibitory effect of anti-adhesion molecule antibodies on eosinophil infiltration in cutaneous late phase response in Balb/c mice sensitized with ovalbumin (OVA).

In this study, we investigated the involvement of the adhesion molecules intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), very late activation antigen-4 (VLA-4), lymphocyte function-associated antigen 1 (LFA-1) and macrophage antigen-1 (Mac-1) on eosinophil infiltration in the cutaneous late phase response (LPR) in OVA-sensitized Balb/c mice by two approaches, immunostaining and inhibition assays with each monoclonal antibody. The eosinophil infiltration into the skin reached a peak at 12 hr after an intradermal challenge with OVA. Infiltrated eosinophils and mononuclear cells in the skin expressed Mac-1 (eosinophils: 38.9 +/- 1.55%, mononuclear cells: 51.2 +/- 2.15%), LFA-1 (eosinophils: 33.3 +/- 0.95%, mononuclear cells: 23.1 +/- 1.07%) and VLA-4 (eosinophils: 14.3 +/- 1.6%, mononuclear cells: 17.2 +/- 1.38%) at 12 h. Intraperitoneal administration of anti-mouse ICAM-1, VCAM-1, and VLA-4 monoclonal antibodies (mAb) before the challenge decreased the eosinophil infiltration by 66.2%, 61.0%, and 54.0%, respectively. On the other hand, pretreatment with anti-mouse LFA-1 mAb or Mac-1 mAb did not significantly decrease the infiltration. These results suggest that VCAM-1/VLA-4 interaction and ICAM-1 play important roles in eosinophil infiltration in cutaneous LPR.

Animals↗

Anti-oxidative therapy with oral dapsone improved HCV antibody positive annular elastolytic giant cell granuloma.

A 72-year-old fisherman who was positive for the HCV antibody developed an annular, erythematous, infiltrated lesions on sun-exposed areas. The lesions were diagnosed as annular elastolytic giant cell granuloma both clinically and histologically. Topical corticosteroid and cryotherapy with liquid nitrogen for several months failed to improve the lesions. We then started dapsone, a known anti-oxidant, at 50 mg/day. A month later, the margins of the erythematous lesions faded, and the infiltration gradually decreased. No recurrence has been observed for one year after the start of the therapy. Anti-oxidative therapy appears to be effective for annular elastolytic giant cell granuloma and could be an alternate therapy for refractory granulomatous disease.

Administration, Oral↗

Hypersensitivity to mosquito bites conceals clonal lymphoproliferation of Epstein-Barr viral DNA-positive natural killer cells.

In order to clarify the relationship between Epstein-Barr (EB) virus and hypersensitivity to mosquito bites (HMB), and to search for the mechanism which induces EB virus-associated lymphoproliferative diseases, we investigated patients with HMB, using hematological, immunological and virological techniques. Among 5 cases of HMB, CD56+ cells had proliferated and CD3+ cells were diminished in 4 cases. Although anti-EB virus antibody titers were not consistent with chronic active EB virus infection, EB viral DNA was detected in the peripheral blood mononuclear cells in all 5 cases. Moreover, EB viral DNA-positive cells had proliferated monoclonally in 4 cases, and biclonally in 1 case. It was proved that most of the EB viral DNA existed in natural killer (NK) cells through polymerase chain reaction analysis. These findings suggest that the basis of HMB may be clonal lymphoproliferation of EB viral DNA-positive NK cells and this hematological abnormality may induce the characteristic symptoms of HMB. In some cases, the proliferating NK cells can metamorphose into leukemic cells, and hemophagocytic syndrome, which has been assumed to be a complication of HMB, may then occur.

Adolescent↗