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T Shiohara

Publications and source records attributed to T Shiohara.

At least 19 recordsLinked to original sources
PubMed2006

Several herpesviruses can reactivate in a severe drug-induced multiorgan reaction in the same sequential order as in graft-versus-host disease.

BACKGROUND: Drug-induced hypersensitivity syndrome (DIHS) is a severe multiorgan systemic reaction. Numerous studies have linked reactivation of human herpesvirus (HHV)-6 with the development of DIHS. Recent articles have suggested that reactivation of other herpesviruses besides HHV-6 might also be involved in the development of DIHS. On the other hand, recent studies have provided evidence for a role of reactivation of various herpesviruses in the development of graft-versus-host disease (GVHD). OBJECTIVES: We attempted to determine whether sequential herpesvirus reactivation could be detected in four patients with severe DIHS, as observed in patients with GVHD, and be coincident with various clinical manifestations that developed after discontinuation of the causative drugs. METHODS: Detection and quantification of viral DNA [cytomegalovirus (CMV), Epstein-Barr virus (EBV), HHV-6 and HHV-7] in sequential blood samples were performed using real-time polymerase chain reaction assays, based on TaqMan technology. RESULTS: In these patients, the cascade of virus reactivation initiated by HHV-6 or EBV extended to EBV or HHV-7, and eventually to CMV. Clinical manifestations of this syndrome followed by failure of various organs occurring despite discontinuation of the drug were coincident with these herpesvirus reactivations. CONCLUSIONS: These results suggest that various herpesviruses can reactivate in the setting of severe drug reactions in a similar sequential order to that described in GVHD. The sequential reactivation of these herpesviruses is responsible for the development of multiorgan failure occurring after discontinuation of the causative drug.

Aged↗
PubMed2006

Dramatic improvement of psoriatic erythroderma after acute hepatitis: analysis of cytokine synthesis capability in peripheral blood T cells.

We report a patient with psoriasis and hepatitis C virus infection who initially presented with psoriatic erythroderma and eventually showed complete clearance of psoriatic lesions following acute hepatitis induced by etretinate treatment. Cytokine synthesis capabilities in peripheral blood T cells obtained at different stages were evaluated in this patient. A dramatic increase in the frequency of interferon-gamma-producing CD8+ T cells in peripheral blood was observed during the erythrodermic stage. In contrast, the frequencies of interleukin (IL)-4- and IL-13-producing CD4+ T and CD8+ T cells were remarkably high at the resolution stage. These results clearly indicate that a shift towards type 2 cytokine predominance contributes to the resolution of severe psoriasis.

Acute Disease↗
PubMed2004

Homing receptor and chemokine receptor on intraepidermal T cells in psoriasis vulgaris.

Intraepidermal T lymphocytes found in psoriatic skin lesions are involved in the development and maintenance of lesional pathology. It has become clear that differential expression of homing and chemokine receptors determines the specific migration of T cells to distinct tissues and microenvironments, including psoriasis lesions. The aim of the present study was to clarify expression of homing (CLA, VLA-4, and LFA-1) and chemokine (CCR4, CCR6, CCR7, and CXCR3) receptors on intraepidermal T cells in psoriatic lesions using flow cytometry. The vast majority of intraepidermal T cells in psoriatic lesions expressed CLA and LFA-1, whereas 58% of CD4+ and 85% of CD8+ T cells expressed VLA-4. The majority of CD4+ T cells and about half of the CD8+ T cells expressed CCR4 and CCR6, whereas less than one-third of CD4+ and CD8+ T cells expressed CXCR3 or CCR7. In patients with psoriasis the percentages of T cells expressing CLA, CCR4, and CCR6 were much higher in the epidermis of psoriatic plaques than in the peripheral blood. Thus, CLA, CCR4, and CCR6 may play a more important role in the migration of T cells to psoriatic epidermis.

Adult↗
PubMed2003

Ebastine inhibits T cell migration, production of Th2-type cytokines and proinflammatory cytokines.

BACKGROUND: Cytokine imbalance and cellular migration to inflammatory sites are critical components of allergic diseases. Redirecting cytokine imbalance and inhibiting cell migration therefore represent important therapeutic strategies for the treatment of these disorders. OBJECTIVES: To study the in vitro effect of ebastine, a novel non-sedating H1 receptor antagonist, on cytokine secretion and migration of activated T cells, as well as production of pro-inflammatory cytokines by macrophages. METHODS: Peripheral T cells obtained from healthy volunteers were cultured in wells coated with the combination of anti-CD3 monoclonal antibody (mAb) and anti-CD26 mAb, anti-CD3 mAb and anti-CD28 mAb, or anti-CD3 mAb with PMA, in the presence or absence of ebastine. T cell proliferation and the production of cytokines were measured by [3H]thymidine incorporation assay and ELISA, respectively. In addition, transendothelial migration of T cells and production of pro-inflammatory cytokines by macrophages were examined. RESULTS: Ebastine inhibited T cell proliferation and the production of IL-4, IL-5, IL-6, and TNF-alpha by T cells under each co-stimulatory condition tested, whereas it exhibited no effect on the production of IL-2 or IFN-gamma. In addition, T cell migration and the production of such pro-inflammatory cytokines as TNF-alpha and IL-6 by macrophages were inhibited by ebastine. CONCLUSIONS: These results indicate that ebastine has a specific inhibitory effect on Th2-type cytokine production. Moreover, ebastine inhibited T cell migration and pro-inflammatory cytokine production by T cells and macrophages, suggesting that ebastine might be useful for the treatment of T cell-mediated allergic inflammatory disorders, including asthma, atopic dermatitis, and Th2-type autoimmune diseases.

Antigens, CD↗
PubMed2002

Protective and curative effects of topically applied CX-659S, a novel diaminouracil derivative, on chronic picryl chloride-induced contact hypersensitivity responses.

BACKGROUND: CX-659S, a newly discovered anti-inflammatory compound, exerts inhibitory effects against acute contact hypersensitivity responses (CHRs) induced by picryl chloride (PC), oxazolone and dinitrochlorobenzene. The murine model of chronic CHR induced by repeated application of PC is known to mimic many, if not all, events occurring within the lesional skin of patients with atopic dermatitis (AD). OBJECTIVES: To investigate the ability of CX-659S to inhibit PC-induced chronic CHR in mice. METHODS: The protective and curative effects of CX-659S were tested on PC-treated ears of BALB/c mice, and were compared with those of prednisolone. Effects were quantified by measurements of ear thickness, serum IgE and cytokine mRNA expression. RESULTS: Both protectively applied and curatively applied CX-659S significantly inhibited increases in ear thickness and total serum IgE. Inhibition was dose-dependent. Although protectively applied prednisolone showed similar activities to CX-659S against chronic CHR, curatively applied prednisolone did not affect the serum IgE level despite inhibiting increases in ear thickness and inflammatory cell infiltration. Consistent with these results, CX-659S reduced mRNA expression of interleukin (IL)-4 and IL-10 but not of interferon (IFN)-gamma, whereas prednisolone inhibited not only mRNA expression of IL-4 and IL-10 but also that of IFN-gamma in the ear lesion. In contrast to prednisolone, CX-659S did not show any side-effect such as atrophy, alopecia or telangiectasia. CONCLUSIONS: CX-659S is the first promising compound having inhibitory activities against chronic CHR accompanied by a diminishing effect on elevated serum IgE, without any other side-effect. Therefore, CX-659S may be a promising candidate for management of patients with recurring AD who require long-term therapy.

Administration, Topical↗
PubMed2002

Preferential expression of alphaEbeta7 integrin (CD103) on CD8+ T cells in the psoriatic epidermis: regulation by interleukins 4 and 12 and transforming growth factor-beta.

BACKGROUND: Intraepidermal T lymphocytes are a critical element for sustaining the lesional pathology of psoriasis. Integrin alphaEbeta7 (CD103), a ligand for E-cadherin, may play a role in the localization of pathogenic T cells within the epidermis of psoriatic lesions. However, little information is available regarding alphaEbeta7 expression on intraepidermal T cells in psoriasis. OBJECTIVES: To examine alphaEbeta7 expression on intraepidermal T cells in psoriatic lesions and the regulation of alphaEbeta7 expression on T cells in response to cytokines. METHODS: T-cell expression of alphaEbeta7 was examined by immunohistochemistry and flow cytometry. In vitro regulation of alphaEbeta7 expression on CD4+ or CD8+ T cells purified from peripheral blood of healthy donors was also examined. RESULTS: Immunohistochemical staining revealed expression of alphaEbeta7 on a greater proportion of epidermal T cells than dermal T cells. Nearly 30% of intraepidermal CD4+ T cells were found to express alphaEbeta7 on flow cytometry, whereas more than 80% of intraepidermal CD8+ T cells expressed this integrin. In contrast, few T cells expressed alphaEbeta7 in the peripheral blood of psoriatic patients. The in vitro culture experiment confirmed that alphaEbeta7 was preferentially expressed on CD8+ T cells after stimulation with anti-CD3 monoclonal antibodies. Addition of transforming growth factor-beta and interleukin-4 upregulated alphaEbeta7 expression on T cells, whereas interleukin 12 downregulated this. Furthermore, alphaEbeta7 expression on established memory CD8+ T cells was not so reversible as that on CD4+ T cells. CONCLUSIONS: Preferential and stable expression of alphaEbeta7 on CD8+ T cells may be involved in the lesional pathology of psoriasis.

Adult↗
PubMed2001

Immunohistochemical detection of skin-homing T cells expressing fucosyltransferase VII (Fuc-TVII) in vitro and in situ.

Although expression of cutaneous lymphocyte-associated antigen (CLA) is thought to be a specific marker of skin "homing" T cells, it has become clear that CLA is a good marker for high levels of fucosyltransferase VII (Fuc-TVII) activity but does not necessarily represent the epitope required for binding to E-selectin (Wagers et al, 1996, 1997). Therefore, expression of Fuc-TVII is an attractive candidate for identifying skin "homing" T cells. However, analyses of Fuc-TVII expression in human T cells have been performed only at the mRNA level (Nakayama et al, 2000) because of the lack of mAB: In this study Fuc-TVII was for the first time visualized in individual cells by using a novel mAb that we developed. Double immunofluorescence and immunohistochemistry demonstrated the coexpression of Fuc-TVII and CLA in cell lines in which Fuc-TVII mRNA was shown to be expressed at high levels: whereas CLA expression was seen in the cell membrane, Fuc-TVII was identified in a supra- or perinuclear location. Cytoplasmic Fuc-TVII expression was also detectable in both CD4(+) and CD8(+) T cells purified from peripheral blood. Fuc-TVII was also expressed at high levels in many CLA(+) T cells infiltrating the skin. In these peripheral T cells, unlike in cell lines, cytoplasmic expression of Fuc-TVII was not always associated with surface CLA expression. This mAb would serve as a valuable tool for selectively identifying a novel subset of skin "homing" T cells that are not detected by the conventional method because of the lack of CLA expression.

Antibodies, Monoclonal↗
PubMed2001

Skin-homing interleukin-4 and -13-producing cells contribute to bullous pemphigoid: remission of disease is associated with increased frequency of interleukin-10-producing cells.

Although evidence is accumulating that type 2 cytokines play a part in the pathogenesis of bullous pemphigoid, little information is available concerning characterization of the cellular source of these cytokines involved in the pathogenesis of bullous pemphigoid. By using multiparameter flow cytometry, we investigated T cells capable of producing interleukin-2, -4, -10, and -13, interferon-gamma, and tumor necrosis factor-alpha and their correlated expression of skin-homing receptor (cutaneous lymphocyte-associated antigen) in peripheral blood and skin blister of patients with bullous pemphigoid. In peripheral blood of bullous pemphigoid patients, significantly increased frequencies of interleukin-4- and interleukin-13-producing cells were found as compared with those of healthy controls, and the majority of these type 2 cells was found in the cutaneous lymphocyte-associated antigen-positive population. The frequency of interferon-gamma-producing cells was also increased as compared with healthy subjects; however, the majority of this subset was found in the cutaneous lymphocyte-associated antigen-negative population. In the skin blister, the frequencies of interleukin-13- and interleukin-4-producing cells were much higher than those in the peripheral blood of bullous pemphigoid, whereas that of interferon-gamma producing cells was significantly lower. Furthermore, in bullous pemphigoid patients after therapy with systemic corticosteroids, the frequency of cutaneous lymphocyte-associated antigen-positive, but not cutaneous lymphocyte-associated antigen-negative, interleukin-13-producing cells was significantly decreased accompanied by an increased frequency of interleukin-10-producing cells, which was associated with clinical improvement. Thus, our results suggest that bullous pemphigoid is a unique organ-specific autoimmune disease characterized by an expansion of skin-homing interleukin-13-producing cells. In addition, corticosteroids may control such type 2 biased inflammatory responses in bullous pemphigoid by promoting the expansion of interleukin-10-producing cells.

Adrenal Cortex Hormones↗
PubMed2001

The cytokine profile in a transient variant of angioedema with eosinophilia.

Episodic angioedema with eosinophilia is characterized by recurrent angioedema, fever and weight gain with a remarkable eosinophilia. A transient type, predominantly reported in Japan, in which the disease is limited to a single attack, is usually less severe than the episodic type described in the U.S.A. and Europe, and provides an ideal disease model in which to study the mechanisms for resolution of eosinophilic inflammation. The aim of this study was to evaluate the relationship between cytokine responses and clinical course in three patients with the transient type. Serum levels of interleukin (IL) -5 were only marginally elevated even during an attack, unlike those in reported cases of the episodic type. Significant elevations in granulocyte-macrophage colony-stimulating factor levels were also noted during an attack in two cases in which it was measured. A dramatic increase in tumor necrosis factor (TNF) -alpha levels was subsequently observed in relation to resolution of clinical symptoms. No major changes in the serum levels of soluble Fas and soluble Fas ligand were found throughout the course. These results suggest that relatively lower levels of IL-5 and a subsequent increase in TNF-alpha levels are characteristic features of the transient type. The differences in clinical symptoms and course observed between the two types may be partly explained by the differences in the cytokine profiles.

Adult↗
PubMed2001

Development and characterization of a monoclonal antibody specific for fucosyltransferase VII (Fuc-TVII): discordant expression of CLA and Fuc-TVII in peripheral CD4+ and CD8+ T cells.

Although cutaneous lymphocyte-associated antigen (CLA) is thought to be specifically expressed on skin "homing" T cells, it has become clear that CLA is not directly involved in binding to E-selectin but represents an excellent marker for high levels of fucosyltransferase VII (Fuc-TVII): Fuc-TVII can regulate the ability of T cells to migrate into the skin by generating a binding site for E-selectin. In this study, by using a novel monoclonal antibody for Fuc-TVII, we investigated whether expression of Fuc-TVII could be selectively detected in various CLA+ cell lines and peripheral blood T cells. Fuc-TVII was readily detected in the cytoplasm, but not in the membrane, of CLA+ cell lines. Cytoplasmic Fuc-TVII expression was also detectable in both CD4+ and CD8+ T cells purified from peripheral blood mononuclear cells. Nevertheless, there were significant numbers of CLA-expressing CD4+ or CD8+ T cells that did not coexpress Fuc-TVII, and vice versa: either the CD4+ or the CD8+ T cell population consisted of a variable ratio of CLA+ Fuc-TVII+, CLA+ Fuc-TVII-, and CLA- Fuc-TVII+ cells; and CLA+ Fuc-TVII- cells were the most abundantly identifiable phenotype in peripheral blood CD4+ and CD8+ T cells. Thus, according to their expression pattern, skin "homing" T cells can be subdivided into at least three populations, CLA+ Fuc-TVII+, CLA+ Fuc-TVII-, and CLA- Fuc-TVII+ cells. Our study provides convincing evidence that skin "homing" T cells are phenotypically heterogenous and that Fuc-TVII expression, in combination with CLA expression, is a useful phenotypic marker for identifying skin "homing" T cells in mixed cell populations.

Antibodies, Monoclonal↗
PubMed2001

Superficial lymphangitis with interface dermatitis occurring shortly after a minor injury: possible involvement of a bacterial infection and contact allergens.

BACKGROUND: Linear supralymphatic eruptions with epidermal involvement have rarely been reported. OBJECTIVE: A search was made for apparent anatomical reasons and for external factors to explain the unique distribution pattern and clinical course in three cases in which the linear lesions occurred shortly after a minor injury. METHODS: Efforts to search for its etiology include careful outlining of the localization, bacterial culture from the site of traumatic injury, patch tests, and skin biopsies. RESULTS: Linear lesions developed along superficial lymphatic vessels and the presence of eczematous conditions around the injured sites and isolation of Staphylococcus aureus from the site were observed concomitantly. The histopathological findings showed interface dermatitis. CONCLUSION: Our cases provide a unique example of the combined effects of a bacterial infection and contact allergens in the development of the linear supralymphatic eruptions.

Adult↗
PubMed2000

Mental stress and physical exercise increase platelet-dependent thrombin generation.

Thrombin generation is an important factor in the pathogenesis of thrombogenic disorders and acute coronary syndromes. Increase in mental stress has been associated with the initiation of the acute coronary syndromes, but the exact mechanism is not known. The present study examined the effects of physical exercise and mental stress on platelet-dependent thrombin generation. Twelve healthy men (mean age 34.2 +/- 2.4 years) underwent a treadmill exercise test and a mental stress test by performing mental arithmetic. Platelet-dependent thrombin generation and plasma concentrations of catecholamines, thrombin-antithrombin III complex (TAT), plasmin-alpha2 plasmin inhibitor complex (PIC), and plasminogen activator inhibitor-1 (PAI-1) were measured before, immediately after, and at 10 and 30 min after stress. Thrombin generation increased significantly immediately after exercise, followed by rapid normalization. Mental stress caused a significant increase in thrombin generation 10 min after stress. While plasma concentrations of epinephrine, norepinephrine, and dopamine were elevated immediately after exercise, and rapidly returned to baseline, only plasma norepinephrine increased immediately after mental stress. TAT and PIC concentrations did increase immediately after exercise; however, PAI-1 remained unchanged. The increase in thrombin generation with exercise and mental stress was unaffected by treatment with 81 mg/day of aspirin of 7 days. However, it was inhibited by a single oral 40-mg dose of metoprolol. Both exercise and mental stress cause an increase in platelet-dependent thrombin generation, which was suppressed by beta-blocker therapy, but not by aspirin.

Adrenergic beta-Antagonists↗
PubMed2000

Virus-induced immune dysregulation as a triggering factor for the development of drug rashes and autoimmune diseases: with emphasis on EB virus, human herpesvirus 6 and hepatitis C virus.

There are a considerable amount of empirical and theoretic medical literature regarding the possible role of viruses in the development of drug rashes and autoimmune diseases: under these conditions, interactions of viruses with the immune system would serve as an accelerating factor of disease pathogenesis. Recent reports have provided evidence to indicate that immune responses against infections with Epstein Barr (EB) virus and human herpesvirus 6 (HHV-6), which are lymphotropic members of the herpes virus group, not only aid the direct elimination of the virus but also contribute to a favorable milieu for the initiation or acceleration of drug rashes. Viruses that can persist for the lifetime of the host despite strong immune responses against them, such as EB virus and hepatitis C virus (HCV), would be also relevant to the pathogenesis of autoimmune diseases. HCV has been reportedly associated with a wide variety of dermatoses that, in common, show histologically the lichenoid tissue reaction. Although porokeratosis that manifests lichenoid histopathological features had long been regarded as being associated with immunosuppression, we found that HCV could act as trigger for the development of porokeratosis during states of immunosuppression. Thus, the main purpose of this review is to describe recent work on the etiology of drug rashes and autoimmune disease with special reference to viral infections.

Autoimmune Diseases↗