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Biomedical subjects

H Yokozeki

Publications and source records attributed to H Yokozeki.

At least 73 records · Page 4Linked to original sources

Granuloma annulare in a patient with malignant lymphoma.

We describe the case of a 69-year-old man with malignant lymphoma who developed granuloma annulare on his fingers. The number of cutaneous nodules increased when a recurrence of lymphoma was demonstrated during the course of disease. Granulomatous lesions disappeared after the fifth cycle of chemotherapy with CHOP (cyclophosphamide, Adriamycin, vincristine, prednisolone). The coexistence of these two diseases is relatively rare. The clinical features seen in this case, however, might suggest that granuloma annulare is a generalized granulomatous reaction induced by malignant lymphoma.

Aged↗

Interferon-gamma differentially regulates CD80 (B7-1) and CD86 (B7-2/B70) expression on human Langerhans cells.

CD80 (B7-1) and CD86 (B7-2/B70) have recently been identified in cultured human Langerhans cells (LCs), although their role and regulatory properties remain unclear. We present our comparison of the expression of the molecules, mRNAs and the function between CD80 and CD86 in human LCs treated by interferon gamma (IFN-gamma). We examined the regulatory properties of CD80 and CD86 expression in human LCs pretreated with IFN-gamma. Flow cytometric analysis indicated that the mean fluorescence intensity of CD86 but not CD80 was enhanced. However, the percentage modulation of both CD80 and CD86 positive cells were significantly up-regulated in a dose-dependent manner, after 48-h culturing with IFN-gamma. The regulatory properties of CD80 and CD86 mRNA expressions in human LC were studied using polymerase chain reaction methods. We found that both CD80 and CD86 mRNA of enriched LCs following IFN-gamma pretreatment for 12 h were higher than those without pretreatment. We have demonstrated that the primary allogeneic mixed epidermal cell-lymphocyte reaction induced by human LCs treated by IFN-gamma increased in a dose-dependent manner. There was a 61.5% inhibition by anti-CD86 monoclonal antibody and a 32.5% inhibition by anti-CD80 monoclonal antibody. These data indicate that the CD80 and CD86 expression of human LCs may be differently regulated by IFN-gamma.

Antigens, CD↗

Functional CD86 (B7-2/B70) is predominantly expressed on Langerhans cells in atopic dermatitis.

Recently, we reported the functional expression of CD86 on cultured human Langerhans cells derived from normal epidermis. In the present study, we investigated the expression and function of co-stimulatory molecules in the pathogenesis of atopic dermatitis. In immunohistochemical analysis, CD80 and/or CD86 were detected on dendritic-shaped cells not only in the epidermis but also in the dermis in the inflammatory lesions of atopic dermatitis (n = 12). CD80 was expressed in only five cases (42%), while CD86 was expressed in all cases (100%). These molecules were not detected in normal control subjects (n = 8). In non-lesional skin of atopic dermatitis (n = 4), CD86 but not CD80 was detected in one case. CD86 was preferentially induced on dendritic-shaped cells in positive patch test sites to Dermatophagoides pteronyssinus or house dust allergen in atopic dermatitis (n = 4). The CD80- or CD86-positive cells were confirmed as Langerhans cells by double immunostaining using anti-CD1a monoclonal antibody. Neither CD86 nor CD80 was detected on keratinocytes. Similar results of the stronger expression of CD86 over that of CD80 were obtained from psoriasis vulgaris (n = 11) and from contact dermatitis (n = 7), although CD86 was expressed only in 57% of the contact dermatitis cases. The percentage of Langerhans cells positive for CD86 was higher than for CD80, i.e. 48% compared with 9%, respectively, in the epidermis of lesional skin of atopic dermatitis (n = 8). The expression rate of these molecules on Langerhans cells increased in the dermis. To investigate the function of co-stimulatory molecules on Langerhans cells in atopic dermatitis, we conducted an inhibition test with antibodies. Anti-CD86 monoclonal antibody almost completely inhibited T-cell proliferation stimulated with crude extract of D. pteronyssinus in the presence of epidermal cells as antigen-presenting cells, whereas anti-CD80 monoclonal antibody produced less of an inhibitory effect. These data indicate that CD86 expressed on Langerhans cells may play an important part in the pathogenesis of atopic dermatitis.

Animals↗

Blockade of costimulatory molecules B7-1 (CD80) and B7-2 (CD86) down-regulates induction of contact sensitivity by haptenated epidermal cells.

The hapten, trinitrobenzene sulphonic acid, induced weak B7-1 (CD80) and moderate B7-2 (CD86) expression on Langerhans cells and mRNA expression of both molecules in organ-cultured murine skin. The intradermal injection of hapten-treated epidermal cells induced hapten-specific contact sensitivity in synergic mice. Cells of the keratinocyte cell line, Pam 212, or epidermal cells treated with a mixture of anti-Ia/thy1.2/gamma delta antibody plus complement, did not show any sensitizing ability. When hapten-treated epidermal cells were injected into mice after incubation with anti-B7-2 (CD86) or B7-1 (CD80) antibody the resultant contact sensitivity reaction was decreased to less than 50% of the control reaction, a reduction which was similar to that seen with the anti-ICAM-1 and anti-LFA-1 antibody-induced inhibition of contact sensitivity. Anti-B7-1 (CD80) or anti-B7-2 (CD86) antibody also inhibited hapten-specific lymphocyte proliferation or the allogenic mixed lymphocyte and epidermal cell reaction in vitro, although the inhibitory effect of anti-B7-1 antibody was not as significant as that of anti-B7-2 antibody. These results indicate that costimulatory signals induced by a hapten on epidermal Langerhans cells play an important role in the induction of hapten-specific contact sensitivity in mice.

Animals↗

Production of chemotactic factor(s) of Langerhans cells by lymph node cells in contact sensitivity.

Langerhans cells (LCs) have to leave the epidermis to migrate into the regional lymph node (LN) after receiving immunogenic signals in contact sensitivity. There should be some molecules responsible for migration of LC in this process. In order to determine whether LN cells can generate such regulatory molecules, we made a search of such molecules in the culture supernatant of LN cells obtained from hapten-painted mice by using a modified Boyden chamber method. The molecule of LC chemotaxis appeared in the culture supernatant at 24 h after hapten painting and its production declined with time thereafter. Antibodies against both ICAM-1 and LFA-1 partially inhibited the chemotactic activity, but this was not the case with anti-TNF-alpha antibody, anti-GM-CSF antibody, fibronectin RGDS. RGES peptide or laminin. The molecule was heat labile and appeared as a molecule of 45-68 kDa on high performance liquid chromatography. Our results suggest that LN cells generate one of the chemotactic molecules of LCs, by which LC can migrate to the regional LN in contact sensitivity.

Animals↗

Superantigen-induced cytokine expression in organ-cultured human skin.

Bacterial superantigen such as staphylococcal enterotoxin B (SEB) induced strong ICAM-1 expression in organ-cultured human keratinocytes. Other superantigens (SEA, SEC1, SEC2) but not mite antigen (Dermatophagoides) also induced ICAM-1 expression both at protein and mRNA level. In contrast to ICAM-1, vascular endothelial cell expression of VCAM-1 was only demonstrated at mRNA level following ICAM-1 expression in keratinocytes. Patterns of cytokine expression in keratinocytes were variable. TNF alpha was strongly expressed in keratinocytes both at protein and mRNA level, while IL1 beta and IL1 alpha were only demonstrated at mRNA level. These results clearly demonstrated that bacterial superantigen could induce cell adhesion molecule expression in keratinocytes through the induction of various cytokines and play an important role in the induction of refractory eczematous lesions in atopic dermatitis.

Adult↗

ICAM-1 expression on keratinocytes in mechanically-injured skin of a patient with atopic dermatitis.

The expression of intercellular adhesion molecule-1 (ICAM-1) on keratinocytes was studied in skin specimens of patch- or scratch-test using Dermatophagoides farinae (DF) antigen in atopic dermatitis (AD). Positive patch test reaction showed exocytosis of lymphocytes and focal expression of ICAM-1 on keratinocytes. Similar lymphocyte infiltration and keratinocyte expression of ICAM-1 were observed in tape-stripped skin which was subjected as the control. In addition, focal ICAM-1 expression on keratinocytes was also observed without exocytosis of lymphocytes. By scratch-test with DF antigen, ICAM-1 expression on keratinocytes was observed in eight out of eleven patients. One specimen showed ICAM-1 expression in spite of the absence of exocytosis of lymphocytes. Two out of three specimens from negative scratch-test sites with control liquid (mixture of equal amount of saline and glycerine) showed ICAM-1 expression in a similar manner to that of the positive scratch tests. In normal control skin, patch-test sites showed focal and weak expression of ICAM-1. Normal appearing skin of AD also showed no ICAM-1 expression. Therefore, in patients with atopic dermatitis, keratinocytes may express ICAM-1 prior to infiltration of lymphocytes into the epidermis and this expression might be induced not only by cytokines produced by lymphocytes but also by mechanically injured (tape-stripped or scratched) epidermal cells.

Adult↗

Functional CD86 (B7-2/B70) on cultured human Langerhans cells.

CD86 (B70/B7-2) has recently been identified as an alternative CD28/CTLA-4 ligand on activated B cells. CD86 has also been demonstrated as possibly serving as a primary costimulatory molecule in the initial immune response. Since the human Langerhans cell is one of the most potent antigen-presenting cells, we examined whether CD86 expression and function are found on organ-cultured skin, freshly isolated Langerhans cells, and cultured Langerhans cells in normal human epidermis. Immunohistochemical study in situ revealed that CD86 was expressed on dendritic cells with CD1a antigen in organ-cultured but not fresh skin. Fluorescence-activated cell sorter analysis revealed that no staining for either CD80 or CD86 was observed in freshly isolated Langerhans cells but that both CD80 and CD86 were expressed on cultured Langerhans cells. The actual expression of CD86 on cultured Langerhans cells was further confirmed by the detection of 70-kDa glycoprotein on Western blot analysis. Analysis of polymerase chain reaction demonstrated that both CD80 and CD86 were specifically amplified from purified cultured and freshly isolated Langerhans cells but not from Langerhans cell-depleted epidermal cells, indicating that both CD80 and CD86 genes were expressed by Langerhans cells. The functional importance of CD86 on Langerhans cells was confirmed by the allogeneic CD4 T cell proliferative responses with enriched Langerhans cells. A monoclonal antibody against CD86 caused 81% inhibition in contrast with 29% inhibition produced by anti-CD80 monoclonal antibody. This inhibitory effect was enhanced to 85.3% inhibition when a combination of anti-CD86 and anti-CD80 was administered. These results indicate that CD86 is predominantly expressed on the surface of cultured Langerhans cells and may transduce a primordial costimulatory signal in the interaction of Langerhans cells and T cells.

Antibodies, Monoclonal↗

Three cases of linear lichen planus caused by dental metal compounds.

Three cases of linear lichen planus on the lower extremities unaccompanied by mucous lesions are described. Dental metal compounds were thought to be the precipitating factor in all cases. Skin lesions did not respond to topical steroid ointment or antihistamines. Two cases showed a positive patch test reaction to gold (HAuCl4) and a positive lymphocyte stimulation test to gold compound (Gold sodium thiomalate). One case showed a positive patch test reaction to mercury (HgCl2), but a negative lymphocyte stimulation test. Suspected metal compounds were demonstrated in their dental materials. Removal of gold materials in one case gradually improved the lesions within 6 months with a transient erythematous swelling of the face shortly after removal of the metal. Both of these cases responded to oral disodium chromoglycate therapy. These results suggest that metal compound specific T cells might be responsible for the development of linear lichen planus.

Adult↗

A case of eosinophilic pustular folliculitis (Ofuji's disease) induced by patch and challenge tests with indeloxazine hydrochloride.

A 73-year-old male developed disseminated erythema over his entire body after exposure to indeloxazine hydrochloride, a cerebral activator. Patch testing with indeloxazine hydrochloride showed a positive reaction, and plaques, vesicles and pustules developed on the face after the patch test. These had the pathologic feature of eosinophilic pustular folliculitis (EPF, Ofuji's disease). A challenge test also provoked eruptions on the face, trunk, arms and legs, which were compatible with EPF. Moreover, both the patch and challenge tests with indeloxazine hydrochloride induced eosinophilia. This is the first report of drug allergy-induced EPF, where drug sensitivity induced an abnormal eosinophilic response mimicking EPF.

Aged↗

Effect of mast cell modulators on IgE-mediated murine biphasic cutaneous reactions.

Hapten-specific and mast cell-dependent biphasic cutaneous reactions were induced by intravenous application of anti DNP-IgE antibodies and a subsequent skin test. These reactions were also demonstrated in SCID mice, which indicates that T cell-mediated immunity might not be involved in these IgE-mediated cutaneous reactions. Simultaneous application of anti histaminics did not suppress these reactions significantly, while several immunomodulators, such as azelastine, FK506, and prednisolone, significantly inhibited both early and late phase reactions except for the failure of FK506 to inhibit the early reaction. Anti-VCAM-1 antibody and anti-tumor necrosis factor-alpha (TNF alpha) antibody but not anti-IL 5 antibody showed similar suppressive effects on both early and late phase reactions. Mast cell and inflammatory cells other than T cells are thought to play an important role in these IgE-induced biphasic reactions. TNF alpha and/or VCAM-1 are required for tissue accumulation of inflammatory cells in this system.

Animals↗

Topical vitamin D3 downregulates IgE-mediated murine biphasic cutaneous reactions.

Hapten-specific and mast-cell-dependent biphasic (immediate and delayed-onset) cutaneous reactions were induced in a murine model by intravenous injection of anti-DNP IgE antibodies followed by a skin test. Four daily applications of topical 1 alpha,24(OH)2D3 ointment significantly inhibited both the immediate and the delayed-onset cutaneous reactions in a dose-dependent fashion, as well as the croton-oil-induced cutaneous reaction and DNFB contact sensitivity reaction. 1 alpha,24(OH)2D3 itself did not show any sensitizing or irritant potential. The inhibitory effect of 1 alpha,24(OH)2D3 on these reactions was limited to the application site and no systemic effect was observed. Another vitamin D3 analog 1 alpha,25(OH)2D3, also showed an inhibitory effect on IgE-mediated cutaneous reactions. These results suggest that topically applied 1 alpha,24(OH)2D3 might modulate IgE-mediated cutaneous reactions and could thus be useful in the treatment of certain human cutaneous disorders other than psoriasis and related keratinizing disorders.

Administration, Topical↗

Incontinentia pigmenti and Behçet's disease: a case of impaired neutrophil chemotaxis.

We describe a patient with incontinentia pigmenti who developed the clinical picture of intestinal Behçet's disease. Diagnosis of Behçet's disease was base on a recurrent genital and oral ulcer and a positive HLA-B51. Impaired neutrophil chemotactic activity and an elevated plasma IL-6 level were found. Chromosomal study revealed no abnormality in the patient or her family. We discuss the possibility that there are common immunological abnormalities in the two syndromes.

Adult↗

The relation between osteoporosis of the spine and osteoarthritis of the knee. A study using dual energy X-ray absorptiometry and radiographs.

We investigated the relation between osteoporosis of the spine and osteoarthritis of the knee using dual energy X-ray absorptiometry of the lumbar spine to measure bone mineral density and radiographs of the knee in 82 randomly selected females (mean age 77.5 years). Radiographs of the knee were divided into a normal and severe group. The bone mineral density of the severe group was significantly more than that of the normal group.

Absorptiometry, Photon↗

Retinoic acid upregulates c-kit ligand production by murine keratinocyte in vitro and increases cutaneous mast cell in vivo.

Mouse-transformed epidermal cell line (Pam 212) generated the soluble mediators for promoting the growth of a mast cell line (MC9) in the presence of retinoic acid at a concentration of 10(-6)-10(-7) M. The effective molecule of MC9 cell growth promoting factor (MC9-GF) was non-dialyzable and eluted between the molecular weight of 45 K and 68 K on a TSK 2000 G column. Chromatofocusing analysis revealed that this factor had a pI range between 7.0 and 7.5. Anti-c-kit ligand antibody abrogated MC9-GF activity and RT-PCR analysis demonstrated that retinoic acid upregulates c-kit ligand mRNA expression by Pam cells. Several recombinant cytokines including IL1-alpha, IL-1 beta, IL-2, IL-3 or IL-4 did not promote MC9 cell growth at a concentration of 100 U/ml. The presence of anti-IL-1 alpha, -IL-1 beta, -IL-2, -IL-3 or -IL-4 antibodies did not abrogate the MC9-GF activity except for anti-c-kit ligand antibody.

Animals↗

Leukemic erythroderma with elevated plasma IL-3 and hyperhistaminemia: in situ expression of IL-3 mRNA in leukemic cells.

We report a case of chronic myelogenous leukemia (CML) with pruritic erythroderma. Hyperhistaminemia, elevated level of plasma interleukin-3 (IL-3), and moderate basophilia were noted in this case. His skin manifestation was resistant to topical corticosteroid therapy and exacerbated in parallel with leukocyte count, plasma histamine and IL-3 levels. To identify localization and production of IL-3 in our case, we performed in situ hybridization on peripheral blood cells and skin biopsy specimen, and detected IL-3 mRNA in myelogenic cells in both specimens.

Dermatitis, Exfoliative↗

Elevated serum CA125 in progressive systemic sclerosis with pleural effusion.

The elevation of tumor markers in benign diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis, or diabetes mellitus has been reported recently. We had the opportunity to observe a female patient with progressive systemic sclerosis (PSS) and pleuritis who demonstrated a high level of CA125 in her pleural effusion and blood serum. The purpose of this report is to describe this case. We also investigated whether tumor markers are elevated in collagen disease. We measured the serum levels of CA125 and CA19-9 in our case of PSS with pleuritis, 27 female patients with collagen diseases including SLE, PSS, dermatomyositis and Sjögren syndrome, and 11 normal females as controls. Compared with the normal controls, there was no evident elevation of CA19-9 or CA125 levels in collagen diseases except in our case. Elevated serum CA125 may be one of the indicators of pleural effusion in collagen disease.

Adolescent↗

Impaired sweating as an exocrine manifestation in Sjögren's syndrome.

To examine the prevalence of hypohidrosis and to quantitate sweating as an exocrinopathy in Sjögren's syndrome (SS), 49 patients with SS (primary form, 38; secondary form, 11) were studied. Sweating was induced by mental stimulation such as deep breathing or hand grasping. Statistically significant reductions of sweat volume were seen in SS (P < 0.005). Patients under 50 years old showed impaired sweat function compared with normal controls (P < 0.0005). In a control study, only haemodialysis patients showed impairment of sweating and this was greater than in patients with SS aged under 50 years. These results suggest that patients with SS develop impaired sweating as an exocrine manifestation in addition to the known symptoms of xerostomia and xerophthalmus.

Adolescent↗