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Biomedical subjects

H Yokozeki

Publications and source records attributed to H Yokozeki.

At least 37 records · Page 2Linked to original sources
PubMed2001

Gammadelta T cells assist alphabeta T cells in the adoptive transfer of contact hypersensitivity to para-phenylenediamine.

Para-phenylenediamine (PPD) is known to be a common sensitizer of allergic contact dermatitis and contact urticaria. To clarify the mechanism of contact hypersensitivity (CHS) to PPD, we established a mouse model of PPD-induced CHS. BALB/c mice were immunized for 3 consecutive days by painting topically a 2.5% PPD solution on their shaved abdominal skin. On days 5, 7 or 9 after the initial application, the mice were challenged by applications of a 2.5% PPD solution. Maximal ear swelling was determined at 24 h but another statistically significant and smaller ear swelling was observed 1 h after challenge with PPD in a hapten-specific manner. Adoptive cell transfer experiments demonstrated that the ear swelling of the adoptive cell transferred mice displayed an early response at 6 h and a late response from 12 h to 24 h when the recipient mice were challenged immediately after transfer. Both MoAbs and complement treatment of the transferred cells demonstrated that the phenotype of the early response cells which elicited a response at 6 h after challenge was Thy1(+), B220(+), alphabeta TCR(-), gammadelta TCR(-), CD3(-), CD4(-), CD5(+) and CD8(-). The in vitro treatment of effector cells with MoAbs against not only alphabeta TCR but also gammadelta TCR, together with complement, was found to diminish substantially the late response, elicited 12-24 h after challenge. Gammadelta T cells reconstituted the ability of alphabeta T cells to transfer 24 h CHS responsiveness. The phenotype of the gammadelta T cells that assist CHS effector alphabeta T cells was CD3(+), CD4(-) and CD8(+) and these regulatory gammadelta T cells were neither Ag-specific nor MHC-restricted. Furthermore, gammadelta T cells from normal spleen could also assist alphabeta T cells in adoptive transfer of the 24 h CHS response in a non-MHC-restricted manner. RT-PCR demonstrated that alphabeta T cells strongly expressed mRNA IFN-gamma, whereas gammadelta T cells expressed not only IFN-gamma but also IL-4 and IL-10. These data indicate that not only early response cells and alphabeta T cells but also Th2 type gammadelta T cells may play an important role in the elicitation of CHS to PPD.

Adoptive Transfer↗
PubMed2001

Unusual annular erythema associated with myelodysplastic syndrome.

We report a case of unusual annular erythema associated with myelodysplastic syndrome (MDS). A 58-year-old male with MDS developed annular erythema on his back, scaly erythema on the dorsa of hands, and exudative erythema on his eyelids. Histological examination revealed a mononuclear cell infiltrate around vessels and follicles in the mid- to lower dermis. He had no history of treatment with granulocyte-colony-stimulating factor (G-CSF). Serum granulocyte-macrophage-colony-stimulating factor (GM-CSF) level was slightly elevated (5.84 pg/ml, normal < 2.0 pg/ml), whereas other cytokines including G-CSF, IL-6, and IL-8 were within normal limits. Skin manifestations were much improved by systemic mepitiostane, and serum GM-CSF level returned to normal levels.

Aged↗
PubMed2000

Regulation of cyclophosphamide-induced eosinophilia in contact sensitivity: functional roles of interleukin-5-producing CD4(+) lymphocytes.

Blood and tissue eosinophilia is obtained when mice pretreated with cyclophosphamide (CY) and sensitized with picryl chloride are challenged on each ear lobe on day 13. To gain important insights into the cellular mechanisms involved in CY-induced eosinophilia in the contact-sensitivity reaction, we examined the cytokine profile expressed in regional lymph node cells and spleen cells. CY pretreatment 2 days before sensitization enhanced expression of IL-4 mRNA in the regional lymph node cells more strongly than expressions of both IL-2 and IFN-gamma mRNA on day 13. Five days after sensitization, spleen cells expressed IL-5 mRNA and produced IL-5 in vitro. Depletion of CD4(+) cells from spleen cells completely abrogated the secretory capacity of IL-5. In vivo blocking of IL-5 on day 3 entirely inhibited spleen, bone marrow, and subsequent blood eosinophilia. When immune lymph node cells prepared on day 13 were stimulated with hapten-modified cells in vitro, the level of IL-4 secreted in the culture supernatant was enhanced by CY pretreatment, but that of IL-2 was not. One important result was that IL-5 was not produced in response to in vitro stimulation, despite the fact that marked eosinophil infiltration in the dermis was observed in vivo. Thus, eosinophilopoiesis was stimulated by IL-5-producing CD4(+) immune T cells that were present in the eosinophil production site, particularly in the spleen before elicitation. In contrast, eosinophil recruitment into the dermis in the efferent phase can be induced without production of IL-5 from lymphocytes.

Animals↗
PubMed2000

Signal transducer and activator of transcription 6 is essential in the induction of contact hypersensitivity.

Contact hypersensitivity (CHS) is thought to be mainly associated with the activation of T helper type 1 (Th1) cells. However, there is also evidence that Th2 cells or Th2 cytokines play a role in the development of CHS. To analyze the functional contribution of Th2 cytokines interleukin (IL)-4 and IL-13, signal transducer and activator of transcription 6 (STAT6)-deficient (STAT6(-/)-) and wild-type (wt) control C57BL/6 mice were contact sensitized with 5% 2,4,6-trinitrochlorobenzene (TNCB), 0.5% 2,4-dinitrofluorobenzene, or 5% 4-ethoxyl methylene-2-phenyl-2-oxazolin-5-one, and any skin reactions were examined. Ear swelling was significantly reduced with a delayed peak response in STAT6(-/)- mice compared with wt mice.A histological analysis revealed that the infiltration of both eosinophils and neutrophils in the skin challenged after 24 h in STAT6(-/)- mice decreased substantially compared with that in wt mice. The expression of Th2 cytokines (IL-4, IL-5) in TNCB-challenged skin tissues and the supernatants from T cells stimulated by 2,4,6-trinitrobenzene sulfonate-modified spleen cells, as well as the immunoglobulin (Ig)E and IgG1 response after challenge, were also profoundly reduced in STAT6(-/)- mice, whereas the expression of interferon gamma was the same in STAT6(-/)- and wt mice after challenge. Furthermore, adoptive transfer experiments revealed that STAT6(-/)- mice induced CHS after injection of lymph node cells obtained from sensitized wt mice. Our data suggest that the STAT6 signal plays a critical role in the induction phase of CHS.

Animals↗
PubMed2000

Multiple minute digitate hyperkeratoses.

A familial case of multiple minute digitate hyperkeratoses is reported. Hundreds of tiny, spiked, keratotic papules were scattered on the trunk and limbs. Microscopically, the lesions showed digitiform orthohyperkeratosis with tenting of the epidermis. Neither atypical epidermal cells nor a dermal infiltrate were observed. This disease has three types: familial, sporadic and postinflammatory. We have analysed the histopathological features of all the cases reported to date. While the familial and sporadic types are similar, the lesions in the postinflammatory type are composed of parakeratotic columns with an invaginated epidermis. Although morphological analysis may not provide any clues to pathogenetic differences, it seems reasonable to assume that the postinflammatory type is an entity different from the other two forms.

Aged↗
PubMed2000

Pathogenic roles of eosinophils in guinea-pig contact sensitivity: regulation of dermal eosinophilia with remotely administered IL-5.

Eosinophils have a variety of functions. Although increasing evidence links the presence of eosinophils to airway damage, studies have not examined in detail if, and how, eosinophils affect skin inflammation. The purpose of this study was to determine whether eosinophil infiltration augments the contact sensitivity reaction in vivo. Guinea-pigs were sensitized with 2, 4-dinitrochlorobenzene and challenged on the dorsal skin or on the right ear lobe. The number of eosinophils and macroscopic changes of the skin lesion in the presence or absence of human recombinant IL-5 (rIL-5) administered at the remote site was assessed. The reaction on the dorsal skin was acutely eczematous with considerable basophil infiltration. In contrast, eosinophils had extensively infiltrated the right ear lobe and major basic protein was deposited in the dermis. A subcutaneous injection of rIL-5 (10 pmol/kg) at the remote site (left ear lobe) 12 h after challenge induced transient blood eosinophilia and enhanced eosinophil accumulation in the challenged ear lobe. These changes were accompanied by increased ear swelling and severe erythema. In contrast, eosinophil infiltration was significantly inhibited by rIL-5 administered at the time of challenge. Ear thickness, as well as the erythema and oedema, were also reduced. These data suggest that marked eosinophil infiltration enhances skin inflammation in allergic contact dermatitis. Moreover, locally administered IL-5 functions remotely by controlling eosinophil recruitment into the skin. The guinea-pig model of contact sensitivity may be useful for evaluating therapies and pharmaceuticals targeted at eosinophil infiltration.

Animals↗
PubMed2000

Glucocorticoids augment the chemically induced production and gene expression of interleukin-1alpha through NF-kappaB and AP-1 activation in murine epidermal cells.

To clarify the mechanism of the glucocorticoid-induced augmentation of skin response, we attempted to demonstrate the modulatory effect of glucocorticoids on the regulation of cytokines produced by keratinocytes stimulated with various chemicals in vitro. Haptens, irritants, and a superantigen (staphylococcal enterotoxin B) induced a significant release of interleukin-1alpha and tumor necrosis factor alpha, but not interleukin-10, from a murine keratinocyte cell line, Pam 212 cells. Glucocorticoids (10(-6)-10(-12) M) significantly augmented the production of interleukin-1alpha by Pam 212 cells at both the protein and mRNA levels when stimulated by either haptens or irritants, but not by staphylococcal enterotoxin B, whereas glucocorticoids alone had no effect. In contrast, glucocorticoids had no effect on the production of tumor necrosis factor alpha and interleukin-10 by chemically stimulated Pam 212 cells. Electrophoretic mobility shift assays revealed that chemical stimulation induced NF-kappaB activation in Pam 212 cells; however, augmented NF-kappaB activation by 10(-6)-10(-8) M of glucocorticoids was observed in Pam 212 cells stimulated by both haptens and irritants, but not by staphylococcal enterotoxin B. Furthermore, pyrrolidine dithiocarbamate inhibited the hapten-induced interleukin-1alpha production and NF-kappaB expression by Pam 212 cells. Pyrrolidine dithiocarbamate did not completely abrogate the hapten-induced interleukin-1alpha production augmented by glucocorticoids, however. To determine the effect on transcription factors other than NF-kappaB, AP-1 activity was examined by electrophoretic mobility shift assays. Hapten was founded to induce AP-1 activation in Pam 212 cells. In addition, AP-1 activation was augmented in the hapten-stimulated Pam 212 cells in the presence of 10(-8)-10(-10) M of glucocorticoids. The augmented inflammatory reaction by glucocorticoids may therefore reflect the augmentation of interleukin-1alpha production by keratinocytes mediated through the NF-kappaB and AP-1 pathway.

Animals↗
PubMed2000

Expression of 27 KD, 65 KD and 72/73 KD heat shock protein in atopic dermatitis: comparison with those in normal skin and contact dermatitis.

The expression of Heat Shock Protein (HPS) 72/73, HSP65 and HSP27 in skin lesions of atopic dermatitis (n = 21) was studied and compared with that in contact dermatitis (n = 18) and normal skin (n = 9). Keratinocytes in the whole epidermis expressed both HSP65 and HSP72/73 with a membranous, cytoplasmic or nuclear/perinuclear staining pattern much more intensely in atopic dermatitis than in contact dermatitis and normal subjects. In approximately half of the subjects with atopic dermatitis, infiltrating cells in the dermis expressed HSP65 and HSP72/73; this was not observed in contact dermatitis. HSP27 was expressed in the upper epidermis with a cytoplasmic or nuclear/perinuclear staining pattern in all groups. HSP27 was not expressed by infiltrating cells. A clinical evaluation of atopic dermatitis showed that more severe types of atopic dermatitis expressed more intense expression of HSP65 and HSP72/73, but not HSP27, in their skin lesions. These findings suggested that HSP65 and HSP72/73 may play roles in the pathogenesis of atopic dermatitis.

Adolescent↗
PubMed1999

Expression of basic fibroblast growth factor and its receptor in angiosarcoma.

Angiosarcoma, a rare aggressive malignant tumor thought to be of vascular origin with high potential for metastasis, frequently occurs on the scalp of elderly people. Recent findings have shown that overexpression of basic fibroblast growth factor and its receptor is associated with neoplasia, which suggests that basic fibroblast growth factor promotes tumor vascularization and subsequent growth. In this study, we examined the immunohistologic localization of basic fibroblast growth factor and its receptor in angiosarcoma. Our results suggest that basic fibroblast growth factor synthesized in the tumor endothelial cells plays an important role in the growth and progression in angiosarcoma and that serum basic fibroblast growth factor levels are elevated in patients with nodular type angiosarcoma.

Aged↗
PubMed1999

IL-4 inhibits the migration of human Langerhans cells through the downregulation of TNF receptor II expression.

The migration of Langerhans cells is an initial event in the sensitization phase of contact sensitivity. Langerhans cells travel from the epidermis to the regional lymph node, and can be variously modulated in the skin where many cytokines are released from epidermal cells, dermal cells, T helper (Th) cells, and other inflammatory cells during the sensitization and elicitation phase of contact dermatitis, and thus induce an altered inflammatory skin reaction. The modulatory effect of the cytokines released in the skin, such as IL-1beta, GM-CSF, and TNF-alpha as epidermal cytokines, IL-2, IL-12, and IFN-gamma as Th1 type cytokines, and IL-4 and IL-10 as Th2 type cytokines, was analyzed using the chemotactic chamber method in this study. Both GM-CSF and TNF-alpha induced the migration of human Langerhans cells in vitro, whereas IL-1beta, IL-2, IL-10, IL-12, and IFN-gamma had no effect on Langerhans cell migration. In contrast, IL-4 inhibited Langerhans cell migration in a dose dependent manner. The inhibitory activity of IL-4 was reversed by both anti-human IL-4 monoclonal antibody and anti-human IL-4 receptor monoclonal antibody. IL-4 inhibited the Langerhans cell migration induced by both TNF-alpha and GM-CSF. Furthermore, anti-TNF-RII monoclonal antibody inhibited both random migration and the migration induced by TNF-alpha, but not that induced by GM-CSF. A reverse-transcriptase-polymerase chain reaction and fluorescence-activated cell sorter analysis revealed that TNF-alpha up-regulated and IL-4 downregulated the TNF receptor II (TNF-RII) expression of Langerhans cells at both the mRNA and the protein levels. The pretreatment of Langerhans cells with TNF-alpha enhanced the migration of Langerhans cells and the expression of TNF-RII. After pretreating Langerhans cells with TNF-alpha, IL-4 inhibited both the migration of Langerhans cells and the expression of TNF-RII in a time dependent manner. These results indicate that IL-4 inhibits the migratory activity of Langerhans cells by downregulating the expression of TNF-RII in human Langerhans cells and thereby modulates the immune response in the skin.

Antibodies, Monoclonal↗
PubMed1999

Cutaneous angiosarcoma with thrombocytopenia.

Thrombocytopenia was observed in 3 patients with cutaneous angiosarcoma of the scalp and face. A sudden decrease in the platelet count occurred in association with rapid enlargement of primary or metastatic lesions. Neither antiplatelet antibody nor platelet-associated IgG was detected. Increased serum levels of beta-thromboglobulin and platelet factor 4 indicated that platelets were destroyed and consumed within the vascular bed of the tumor. Prominent PECAM-1 expression on tumor cells may be involved in intratumoral platelet aggregation and consumption. We suggest that the sudden development of profund thrombocytopenia in patients with angiosarcoma may suggest either rapid growth of the primary tumor or herald the development of metastatic disease.

Aged↗
PubMed1999

Heat shock proteins and skin diseases.

Heat shock proteins are chaperones to construct protein molecules and are widely distributed in prokaryotic and eukaryotic cells. They are also induced by environmental stress to protect cells. Human heat shock proteins cross-react with bacterial heat shock proteins to modulate immune responses to induce autoimmunity. They are involved in the differentiation and growth of neoplastic cells as well as normal cells. They are also involved in various inflammatory skin diseases and in fibrotic process. Heat shock proteins play important roles in the pathogenesis of many skin diseases.

Journal Article↗
PubMed1999

Cataract and retinal detachment in patients with severe atopic dermatitis who were withdrawn from the use of topical corticosteroid.

Many patients with severe atopic dermatitis (AD) in Japan are afflicted with persistent erythema of the face (atopic red face) that is not only resistant to topical corticosteroid, but often becomes worse with its use. During a three-year period (1991-1993), we treated 79 inpatients with severe AD by a combination of careful daily skin care, use of emollients, and exclusion of exacerbating factors. Occular complications before and after treatment were examined in these cases. After withdrawal of topical corticosteroid, almost all of the patients showed a temporary worsening of their skin condition. Immediately thereafter, their occular symptoms did not change. Cataract was found in 20 cases (25.3%), and retinal detachment in 9 (11.4%). After 2 months, 11 cases of cataract and 5 cases of retinal detachment in the peripheral retina were observed. However, these incidences were similar to the numbers reported in Japan during conventional treatment with topical corticosteroid. The development of cataract or retinal detachment had no relationship to serum IgE levels, personal history of respiratory atopy, the duration of topical corticosteroid use on the face, or treatment with systemic corticosteroid. Our observations suggest that patients who habitually tap or rub their faces strongly tend to develop cataract or retinal detachment at a statistically significant higher frequency. Patients with AD should have ophthalmologic examinations every one to two months for at least one year after a facial oozing attack or withdrawal of corticosteroid.

Administration, Topical↗
PubMed1999

Treatment of reticular erythematous mucinosis with a large dose of ultraviolet B radiation and steroid impregnated tape.

To date, there are no successful treatments for reticular erythematous mucinosis (REM) other than antimalarial drugs such as chloroquine; these have many adverse side effects and are prohibited for use in Japan. We report a case of REM improved by a large dose of ultraviolet B (UVB) radiation and a steroid impregnated tape. The large dose of UVB radiation improved the erythema after 5 weeks. Application of steroid impregnated tape to a lesion where a large dose of UVB had been given produced an additive clinical effect. UVB radiation and steroid impregnated tape are considered to be effective treatments for REM.

Combined Modality Therapy↗
PubMed1999

Skin invasion of Hodgkin's disease mimicking scrofuloderma.

We report a case of direct skin invasion by Hodgkin's disease from a left supraclavicular lymph node. Clinical and pathological presentations mimicked infectious disease such as scrofuloderma. The nodule later developed a fistula following a biopsy that never healed despite numerous antibiotic treatments. Ten months later, other nodules with spontaneous fistula formation appeared on the anterior neck. A diagnosis of Hodgkin's disease was then made. Subsequent COPP cytostatic therapy remarkably improved the skin lesions and lymph nodes achieving complete remission.

Aged↗
PubMed1999

[Postoperative prophylactic intravesical instillation of tetrahydropyranyl-adriamycin (THP) for superficial bladder cancer].

Intravesical instillation of tetrahydropyranyl-adriamycin (THP) was performed on 51 patients with superficial bladder cancer after transurethral resection (TUR) for prophylaxis of recurrence. The instillation was carried out with 20 mg of THP dissolved in 40 ml of distilled normal saline. Instillation was performed once 24 hours postoperatively, 9 times every 2 weeks, and 8 times every 4 weeks. These drugs were instilled for 30 to 60 minutes. The recurrence-free survival at 1, 2 and 3 years was 74.5%, 64.6% and 58.0%, respectively. Side effects of THP instillation were observed in only 4 cases (7.8%) as slight urinary frequency or micturition pain. Cases involving 5 or more tumors, or tumors measuring 3 cm or larger, more frequently demonstrated recurrence. The cases that did not respond to preoperative intravesical instillation of THP demonstrated a high frequency of recurrence. Intravesical instillation of THP as a prophylaxis against recurrence of superficial bladder cancer was effective in selected patients.

Administration, Intravesical↗