[Contact dermatitis].
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Biomedical subjects
Publications and source records attributed to Hiroo Yokozeki.
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PD-1 and its ligands, B7-H1/PD-L1 and B7-DC/PD-L2, have been identified recently as CD28-B7 family molecules that are implicated in immune regulation. Lichen planus (LP) is a T cell-mediated chronic inflammatory mucocutaneous disease. We investigated the expression and function of PD-1 and its two ligands in LP. Immunohistochemical examination revealed the abundant expression of PD-1 and B7-H1 in infiltrating T cells and macrophages, and lower-level expression of B7-DC on macrophages in the subepithelium. Interestingly, substantial expression of B7-H1 on keratinocytes (KCs) was found close to the numerous T cell infiltrates in the subepithelium. Unstimulated cultured KCs expressed both B7-H1 and B7-DC, and their expression was upregulated by proinflammatory cytokines, particularly IFN-gamma. The T-cell proliferative responses and IFN-gamma production that were induced by IFN-gamma-treated KCs were augmented preferentially by anti-B7-H1 mAb, but not by anti-B7-DC mAb. These results indicate the regulatory role of B7-H1 on KCs in the interactions with T cells. Our results suggest that the induction of B7-H1 on KCs may play an important role in tolerance induction in the inflamed oral mucosa and skin.
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A case of eccrine porocarcinoma with Bowenoid changes is reported. We compared the results of immunohistochemical staining for epithelial membrane antigen in the present case with results in Bowen's disease to determine whether the presence of epithelial membrane antigen (EMA) enabled us to differentiate between Bowen's disease and eccrine porocarcinoma with Bowenoid changes. Histologically, the present tumour was characterized by atypical clear cells with Bowenoid changes as well as uniform small cells and intradermal nests with ductal structures. The membrane and cytoplasm of uniform small cells and ductal luminal surfaces were positive for EMA. However, the atypical cells with Bowenoid changes were negative for this. In contrast, tumour cells in Bowen's disease were positive for EMA. Although EMA is known to be a useful marker for some benign tumours derived from eccrine ducts, we found it difficult to distinguish eccrine porocarcinoma with Bowenoid changes from Bowen's disease using immunohistochemical staining for EMA.
Antiallergic drugs and antihistamines have been widely used for controlling mucosal allergic diseases in which eosinophilia is prominent. Although H1-receptor antagonists are effective for treating histamine-induced wheal and itch in urticaria, the effects of antihistamines and antiallergic agents on other eosinophilic skin diseases remain to be determined. We investigated the effects of oral administration of antiallergic drugs and antihistamines, such as suplatast tosilate, emedastine difumarate, and azelastine hydrochloride, on a novel murine model of eosinophilia in contact sensitivity to picryl chloride. Among the drugs tested, only suplatast tosilate remarkably inhibited blood and tissue eosinophilia and the ear swelling responses. The inhibitory effects on eosinophilia seemed to be mediated by the suppression of IL-5 production in spleen cells during eosinophil development, while the effects on the ear swelling response seemed to be mediated by suppression of IL-4 production in immune lymph node cells in the efferent phase. Suplatast tosilate may effectively treat eosinophilic skin diseases in which Th2-cell-derived cytokines are predominant.
Three cases of palpebral edema associated with Graves' disease are described. These patients had unilateral edema and minimal erythema of the upper eyelid. Notable was that, histologically, dermal edema and dilation of lymphatic vessels were observed, but deposition of mucopolysaccharides was not. In 2 cases, edema of the eyelid was resistant to treatment with an antithyroid drug. Unilateral edema of the upper eyelid is an important cutaneous manifestation that indicates the presence of hyperthyroidism.
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Leukocyte extravasation is initiated by interaction with endothelial selectins through selectin ligands. To understand the relative roles of E- and P-selectin in eosinophil recruitment in inflamed skin, we examined the expression of sialyl-Lewis x (sLex) structures and selectin ligands on eosinophils from patients with atopic dermatitis using whole blood flow cytometry. None of the eosinophils from the blood of patients expressed HECA452 (a lymphocyte receptor for skin homing) or CSLEX1 epitopes, and they had little avidity for soluble E-selectin. Whereas levels of the FH6 epitope (sialyl-dimeric Lex) varied on blood eosinophils, none of the infiltrative eosinophils in the skin lesions of patients expressed any type of sLex structures on the surface. In contrast, blood eosinophils bound to soluble P-selectin. The amount of P-selectin that bound to eosinophils was significantly greater in patients with atopic dermatitis than in healthy donors. PSGL-1 expression between these two groups did not differ. Furthermore, eosinophils expressed a large amount of alpha (1, 3) fucosyltransferase (FucT)-IV mRNA, but remarkably little or no FucT-VII mRNA compared with neutrophils. These data indicate that eosinophil interaction with endothelial P-selectin is far more important than interaction with E-selectin for recruitment into the inflamed skin of patients with atopic dermatitis. None of HECA452, 2H5, CSLEX1 or FH6 antigens functioned as a specific receptor to promote preferential skin infiltration via adhesion to endothelial E-selectin. FucT-IV in eosinophils may be more relavent to the generation of functional P-selectin ligand than FucT-VII.
Five patients with chronic pigmented purpura associated with odontogenic infection are described. Four patients had Schamberg's disease, and one had itching purpura. These patients were resistant to topical corticosteroid treatment, but appearance of purpuric spots ceased after treatment for periodontitis, pulpitis, or both. No circulating immune complexes were detected, and neither immunoglobulin nor complement was deposited in the papillary vessels of the skin. Odontogenic infection might be one of the precipitating factors for chronic pigmented purpura.
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We report a case of Kikuchi's disease (histiocytic necrotizing lymphadenitis) in a 22-year-old Japanese man who presented with cervical and axillary lymphadenopathy and who developed edema of lips with desquamation and erosions and transient indurated erythematous papules on the face, neck and upper extremities. A lymph node biopsy specimen showed the typical necrotizing lymphadenitis of Kikuchi's disease. A skin biopsy specimen showed a dense, lymphohistiocytic, superficial, deep perivascular, and interstitial infiltrate, papillary dermal edema, and abundant nuclear debris with a conspicuous absence of neutrophils, paralleling the nodal histology of Kikuchi's disease. CD68 immunohistochemistry showed many plasmacytoid monocytes. Oral corticosteroid (prednisolone 40 mg) therapy improved the skin lesions and other clinical symptoms. Lip involvement by Kikuchi's disease has not been reported, and should be included as one of the possible cutaneous manifestations of Kikuchi's disease.
We herein report six cases of localized involutional lipoatrophy, who presented with a depressive plaque on the lateralis of the upper arm. All patients were female, and three had previous injections for allergic rhinitis at the affected sites before the development of lipoatrophy. One patient received intramuscular injection at the affected site when she had a cold. Histological examination showed fat lobules composed of small lipocytes in the hyaline connective tissue. Immunohistochemical examination revealed a number of CD68-positive macrophages in the fat lobules. We consider that localized involutional lipoatrophy is more common than has been reported, and is occasionally induced by local injections.
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To investigate the mechanism of the glucocorticoids-induced augmentation of skin response, we have recently reported the modulatory effect of glucocorticoids on the regulation of cytokines production in keratinocytes stimulated with various chemicals in vitro through both NF-kappaB and AP-1 activation. Further to clarify the mechanism in the glucocorticoids-induced augmentation of cytokines production from keratinocytes, we examined the effect of glucocorticoids to keratinocytes without chemical stimulation. Glucocorticoids 10(-4) M inhibited the production of IL-1alpha from Pam 212 cells. However, lower concentration (10(-8)-10(-10) M) of glucocorticoids significantly enhanced the production of IL-1alpha by Pam 212 cells at both the protein and mRNA levels. In contrast, glucocorticoids had no effect on the production of either TNF-alhpa, IL-6, nor GM-CSF by Pam 212 cells cultured for 6 h. Electrophoretic mobility shift assays (EMSA) revealed that 10(-10)-10(-12) M glucocorticoids induced the NF-kappaB activation in Pam 212 cells, however, augmented AP-1 activation by 10(-8)-10(-10) M of glucocorticoids was observed in Pam 212 cells. Furthermore, pyrrolidine dithiocarbamate (PDTC) partially inhibited the IL-1alpha production and completely inhibited NF-kappaB expression by Pam 212 cells. On the other hand, MAP-kinase inhibitors (PD98059, SB202190) completely abrogated not only AP-1 activation but the low concentration glucocorticoids-induced IL-1alpha production. These data indicated that lower concentration of glucocorticoids induced the augmentation of IL-1alpha production from keratinocytes mediated through the AP-1 pathway and partially through NF-kappaB pathway.
A 62-year-old man with amyloid deposition associated with generalized morphea-like scleroderma is described. He had been occupationally exposed to organic solvents. Physical examination showed sclerosis of fingers, forearms, and trunk. Erythema was noted on the border of patchy sclerotic plaques on his chest and back. In addition, firm miliary, keratotic papules were found on the lateral forearms. Amyloid deposition was demonstrated by Congo-red stain at papillary layers of overlying sclerotic dermis in the biopsied specimen taken from the left forearm. As far as we know, amyloid deposition associated with generalized morphea-like scleroderma has not been reported until now.
A case of pigmented purpuric eruptions evolving to mycosis fungoides during the 4-year follow-up period is described. Clinical manifestation was characterized by petechial lesions with irregular shaped, diffusely pigmented plaques partly sharing morphological similarities with chronic pigmented purpura. Histologically, lymphocytes infiltrated around the capillaries of the superficial dermis with extravasated erythrocytes as well as into the epidermis to form Pautrier microabscesses. Whereas CD4+ cells were observed in the epidermis and upper dermis, CD8+ cells tended to be distributed around the capillaries. Notably, the Rumpel-Leede test revealed extensive punctuate purpura limited to the lesional skin. The aggregation response of platelets was not impaired. Either CD4+ tumor lymphocytes or CD8+ reactive lymphocytes appeared to induce capillary damage resulting in the formation of petechial lesions. Pigmented purpuric eruptions, such as atypical chronic pigmented purpura, is thus an important initial clinical manifestation of mycosis fungoides.