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Biomedical subjects

S Aiba

Publications and source records attributed to S Aiba.

At least 55 records · Page 3Linked to original sources

Dendritic cells differently respond to haptens and irritants by their production of cytokines and expression of co-stimulatory molecules.

After application of haptens to the skin, Langerhans cells (LC), i.e. immature dendritic cells (DC) in the skin, move to secondary lymphoid organs to sensitize naive T cells. During this process, LC become mature DC with augmented expression of various co-stimulatory molecules and MHC class II antigens. In this scenario, however, critical questions remain as to what kind of chemicals can induce this maturation process through what kind of mechanisms. To clarify these questions, we used monocyte-derived CD1a+ DC instead of LC since LC maturated spontaneously in vitro culture. After we confirmed that monocyte-derived DC showed at least phenotypic characteristics and a response to TNF-alpha similar to LC, we added various chemicals, i.e., dinitrochlorobenzene (DNCB), trinitrochlorobenzene (TNCB), NiCl2, ZnCl2, sodium dodecyl sulfate (SDS), or benzalkonium chloride (BC), to a culture of purified monocyte-derived CD1a+ DC. Of these chemicals, only NiCl2 and DNCB significantly increased the surface expression of CD54, CD86, HLA-DR antigen, and interleukin (IL)-1 beta production, while SDS, BC, or ZnCl2 could not augment them, except for weak augmentation of CD86 expression by SDS. The increase in the expression of CD86 induced by NiCl2 or DNCB was most remarkable, being observed in DC from almost all the subjects we examined. TNCB could also induce responses similar to those induced with DNCB, but the number of subjects whose DC responded to it was far less than that of subjects whose DC responded to NiCl2 or DNCB. In spite of the augmented CD86 expression on DC treated with DNCB or NiCl2, these chemicals induced different responses of DC in their expression of CD54 and HLA-DR and the production of IL-6 and tumor necrosis factor (TNF)-alpha. In addition, the up-regulation of CD86 expression on DC treated with DNCB was significantly suppressed by either anti-IL-1 beta or anti-TNF-alpha antibody, while that by NiCl2 was relatively insensitive to these antibody treatments. Finally, the protein kinase C inhibitor, H7, but not staurosporine, could suppress the augmentation of CD86 expression on DC induced either by NiCl2 or by DNCB. These data suggest that DC respond to some haptens by changing their expression of several co-stimulatory molecules and their production of cytokines with a resultant change in antigen-presenting function. They also suggest that these chemicals stimulate DC by different mechanisms. By these responses, DC may modulate the final immune response to chemicals.

Antibodies↗

Inverse correlation between CD34 expression and proline-4-hydroxylase immunoreactivity on spindle cells noted in hypertrophic scars and keloids.

The CD34 positive (CD34+) spindle cells constitute a special population of spindle cells which shows a unique distribution in the skin. So far, however, the functional role of CD34+ spindle cells and the regulation of CD34 expression on dermal spindle cells are totally unknown. We examined immunohistologically the pattern of the expression of CD34 and proline-4-hydroxylase, a marker for the fibroblasts that participate in active collagen synthesis, on dermal spindle cells at various stages of scar and keloidal tissues. Dermal spindle cells in the lesions of hypertrophic scar and those at inflammatory expanding borders of keloids totally lost CD34 expression, but they strongly expressed proline-4-hydroxylase. On the other hand, they expressed CD34, together with decreased immunoreactivity to anti-proline-4-hydroxylase antibody, in non-inflammatory scars or in a non-inflammatory central portion of keloid. In two cases of scars, in which inflammation began to subside, double immunofluorescence demonstrated that both CD 34 and proline-4-hydroxylase were expressed on the same spindle cells. CD34 expression, once disappeared from the lesions of hypertrophic scar or keloid, seems to return on CD34-proline-4-hydroxylase+ cells, when the initial inflammatory changes begin to regress. There is a reverse correlation between CD34 expression on spindle cells and the synthesis of type I collagen in the skin.

Adolescent↗

Expression of CD34 in glomus tumors.

Immunohistochemical studies were performed in order to characterize glomus tumors. In all cases the glomus tumor cells stained positively for smooth muscle actin. In half of six cases, the glomus tumor cells weakly expressed desmin. They were not reactive with Ulex europaeus agglutinin-I and anti-Factor VIII-related antigen, whereas the only endothelial cells were reactive with them. The tumor cells as well as vascular endothelial cells amongst the tumor cells expressed CD34 in five of the cases.

Adolescent↗

Comparison of immune reactivity profiles against various environmental allergens between adult patients with atopic dermatitis and patients with allergic respiratory diseases.

To clarify the pathomechanisms underlying the involvement of different organs by atopic dermatitis (AD) and allergic respiratory disease (ARD), we compared the immune reactivities to various environmental allergens between 46 adult patients who suffered only from AD but were without any history of ARD and 41 patients who had only ARD, using a RAST FEIA (radioallergosorbent test/fluoroenzyme immunoassay) and a scarification patch test. We also studied 42 healthy adult subjects in a similar fashion. Total serum IgE antibody levels were found to be far higher in the AD group than in the ARD and healthy control group, and RAST revealed that the AD group was sensitized to far larger numbers of allergens such as food mix, cereal mix, fungus mix and Candida albicans than were the other groups. The ARD group displayed a high incidence in RAST, comparable to that of the AD group, only against Japanese cedar and grass pollen mix antigen. However, the most remarkable difference in the immune reactivity profiles was that the AD group showed a uniquely higher RAST score and a lower incidence of positive patch test reactions to C. albicans antigen than did the ARD group. The reactivities in the ARD group to C. albicans antigen did not differ from those in the control group. Our present data suggest that a more pronounced shift from Th1 to Th2 cells, reactive against various allergens, takes place in AD patients.

Adolescent↗

Interferon-gamma and interleukin-10 inhibit antigen presentation by Langerhans cells for T helper type 1 cells by suppressing their CD80 (B7-1) expression.

CD80(B7-1) and CD86(B7-2) co-stimulatory molecules have been reported to activate Th1/Th2 development pathways differentially. It is well known that Langerhans cells (LC), potent antigen-presenting dendritic cells in the epidermis, express several co-stimulatory molecules and that this expression is modulated by several cytokines. Based on the recently reported effect of interferon (IFN)-gamma and interleukin (IL-)-10 on the expression of CD80 and CD86 by LC, we examined the effects of these cytokines on the expression of CD54 (intercellular adhesion molecule-1) and CD40 in addition to CD80 and CD86 on LC, and correlated the expression of each co-stimulatory molecule with antigen presentation for a Th1 clone by cultured LC (cLC) treated with these cytokines. LC cultured for 72 h significantly up-regulated MHC class II antigen expression and all the co-stimulatory molecules were examined. As previously reported, IL-10 or IFN-gamma inhibited the up-regulation of CD80 expression. Granulocyte/macrophage-colony-stimulating factor (GM-CSF) partially restored the suppression of CD80 expression induced by IFN-gamma on cultured LC, while it had virtually no effect on the inhibition induced by IL-10. Antigen presentation for the myoglobin-specific syngeneic Th1 clone by cLC, which were pre-incubated with these cytokines, correlated well with their CD80 expression. In addition, among the antibodies for CD80, CD86, CD28 or CD40, the suppression of the Th1 clone stimulation by LC was found to occur only with anti-CD80 and anti-CD28 antibodies. Finally, we studied the effects of IFN-gamma and IL-10 on GM-CSF production by epidermal keratinocytes (KC). We could show that only IFN-gamma, but not IL-10, suppressed GM-CSF production by KC. These findings suggest that both IFN-gamma and IL-10 suppress antigen presentation by LC for Th1 cells by suppressing their CD80 expression. The inhibitory effect of IFN-gamma on CD80 expression on LC appears to be partially mediated through the suppression of GM-CSF production by KC.

Animals↗

Reduced proliferative responses of peripheral blood mononuclear cells specifically to Candida albicans antigen in patients with atopic dermatitis--comparison with their normal reactivity to bacterial superantigens.

Although reduced cutaneous reactivities to Candida albicans have been reported in patients with atopic dermatitis (AD), there is still controversy as to whether the in vivo lymphocyte proliferation response is normal or reduced. We have also reported that patients with AD manifest a decreased cutaneous response only to C. albicans antigen in scarification patch tests. The purpose of this study was to examine whether patients with AD show normal lymphocyte transformation responses to C. albicans antigen. Peripheral blood leucocytes (PBL) from 21 patients with AD and 14 healthy control (HC) subjects were cocultured with optimal concentrations of C. albicans antigen and of superantigens (staphylococcal enterotoxin A and B). PBL from the patients with AD showed a significantly lower response to C. albicans antigen, but there was no statistically significant difference in PBL responses to superantigens between the patients with AD and the HC subjects. This decreased proliferative response of PBL was particularly noticeable in those whose RAST scores for C. albicans antigen were high. These results suggest the development of a specific anergy to C. albicans antigen in patients with AD.

Adolescent↗

Chemical modification of silk fibroin with N-acetyl-chito-oligosaccharides.

N-Acetyl-chito-oligosaccharides (NACOS)-silk fibroin (SF) conjugates (NACOS-CY-SF) were prepared by the reaction of solubilized SF and cyanuric chloride (CY)-activated NACOS modifier (NACOS-CY). N-Acetyl-D-glucosamine (NAG), as a model compound, was reacted with CY to clarify the chemical structure of the modifier. The 1H- and 13C-NMR spectra of the reactant suggest that the anomeric hydroxyl group of NACOS reacted with the chlorine atom of CY. The content of NACOS in the NACOS-CY-SF conjugates was calculated by comparing the integral values of the signals in the 1H-NMR spectra of the conjugates and the mixture of NACOS and SF. As the 1H-NMR spectrum of the conjugates showed a downfield shift of the aromatic protons of the tyrosine residue, the tyrosine residue in SF reacted with another chlorine atom of the triazine ring of the modifier. The result of the amino acid analysis of the conjugates suggests that lysine residues also reacted with the modifier.

Acetylglucosamine↗

Interleukin-1 beta and granulocyte-macrophage colony-stimulating factor mediate Langerhans cell maturation differently.

It has been reported that the in vivo maturation of Langerhans cells after hapten painting is mediated by IL-1 beta while Langerhans cell maturation after in vitro culture is mediated by granulocyte-macrophage colony-stimulating factor (GM-CSF). To clarify the reason for this discrepancy, we examine the expression of Ia antigen and several co-stimulatory molecules on Langerhans cells that were activated by in vitro culture, by hapten painting, or by an intradermal injection of several cytokines. Both cultured Langerhans cells and those activated by hapten painting increased the expression of Ia antigen and all the co-stimulatory molecules (i.e., intercellular adhesion molecule-1 [ICAM-1], B7-1, B7-2, and CD40). In contrast, an intradermal injection of interleukin-1 beta (IL-1 beta) or tumor necrosis factor-alpha (TNF-alpha) increased the expression of Ia antigen, ICAM-1, B7-2, and CD40, but not that of B7-1. These data indicate that IL-1 beta or TNF-alpha is not sufficient to induce B7-1 expression on Langerhans cells in vivo. Subsequently we examined the effect of anti-cytokine antibodies (Abs) on the expression of those molecules on cultured Langerhans cells. While none of the Abs to IL-1 beta, TNF-alpha, or GM-CSF changed the upregulation of Ia antigen, ICAM-1, or CD40 on cultured Langerhans cells, anti-GM-CSF Ab suppressed that of B7-1 and B7-2. Taken together, our present results suggest that IL-1 beta is required for the upregulation of Ia, ICAM-1, B7-2, and CD40, while GM-CSF is required for the upregulation of B7-1 and B7-2, although it still remains unclear why the injected GM-CSF could not augment B7-1 expression on Langerhans cells in vivo and why anti-IL-1 beta Ab did not suppress the upregulation of Ia, ICAM-1, or CD40 on cultured Langerhans cells.

Animals↗

Expression, but lack of calcium mobilization by high-affinity IgE Fc epsilon receptor I on human epidermal and dermal Langerhans cells.

In atopic dermatitis (AD) patients, IgE molecules are demonstrated on the surface of Langerhans cells (LC). Fc epsilon RI molecules, which are present on the surface of LC in AD patients as well as normal individuals, are responsible for this binding. In this study, we have investigated phenotypic and functional characteristics of Fc epsilon RI on epidermal and dermal cell populations. Epidermal and dermal cell suspensions were prepared enzymatically with dispase followed by either trypsin or collagenase treatment, respectively. Peripheral blood basophils were negatively selected by excluding other leukocytes with surface marker staining. Consistent with previous reports, both peripheral blood basophils and epidermal LC were positively stained with anti Fc epsilon RI monoclonal antibody. In addition, an Fc epsilon RI positive population was demonstrated among dermal HLA-DR positive cells. These cells express significant amounts of HLA-DR molecules (DRHi) and co-express CD 1 a molecules, which identifies them as LC-like dendritic APC of the dermis. No other Fc epsilon RI positive population was found in the other dermal DRMid or DR- populations, except for a minor DRLo population, presumably mast cells. To analyze whether these Fc epsilon RI molecules are signal transducing for LC, intracellular calcium mobilization after crosslinking of Fc epsilon RI was measured with flow cytometry. Following crosslinking, peripheral blood basophils clearly increased intracellular calcium. On the other hand, neither normal epidermal LC nor dermal DRHiCD1a + cells changed their intracellular calcium level after Fc epsilon RI crosslinking. These data indicate that normal epidermal and dermal LC, but not basophils, are resistant to calcium flux following Fc epsilon RI engagement.

Adult↗

Pulmonary interstitial emphysema during piston-type high-frequency oscillatory ventilation.

We retrospectively reviewed data on high frequency oscillatory ventilation (HFOV) settings and pulmonary function in 14 extremely low birth weight infants who were treated with piston-type HFOV immediately after birth for severe respiratory distress to investigate the cause of pulmonary interstitial emphysema (PIE) associated with HFOV. PIE developed a mean of 23 hr after the initiation of HFOV in 6 infants. Eight infants did not develop PIE and served as the control group. The lowest mean airway pressure (MAP) in the PIE group, which occurred immediately before disease onset was 5.2 cm H2O. The lowest MAP in the control group was 7.5 cm H2O (p < 0.01), which occurred immediately before the ventilatory mode was changed from HFOV to conventional mechanical ventilation for weaning from mechanical ventilation. Respiratory system compliance (Crs) 12 hr after birth was below normal in both groups and there was no significant difference between groups. These results suggest that an unusually low MAP may contribute to PIE during piston-type HFOV in the presence of low Crs. It is therefore important to maintain a high MAP during HFOV until pulmonary compliance becomes normal.

Blood Gas Analysis↗

Oral prednisone in the treatment of acne agminata.

Acne agminata (lupus miliaris disseminatus faciei), once regarded as a tuberculide, is a facial granulomatous disease still seen in young adults in Japan, despite a decrease in the incidence of tuberculosis. Although most lesions regress within a few years, even without treatment, disfiguring scars remain on the face. We have evaluated the efficacy of low dose oral prednisone therapy because, in the past, there has been no satisfactory therapy for this condition. We have treated four patients with acne agminata with prednisone, at first 10 mg daily for 2 weeks, decreasing to 5 mg daily for 3 months. This modest dosage was found to give an excellent result in three patients and a poor result in one whose treatment was started at a much later stage of the disease than in the others. Acne agminata can be cured without scar formation when oral steroids are started in an early phase of the disease.

Administration, Oral↗

Attachment and growth of fibroblast cells on silk fibroin.

The attachment and growth of fibroblast cells (L-929) on matrices of silk fibroin from Bombyx mori domestic silkworm (DSF) and Antheraea pernyi wild silkworm (WSF) were studied by a cell culture method. The performance of the two kinds of silk fibroin was compared to that of collagen. DSF exhibited as high a cell attachment and growth as collagen did. The cells attached to DSF were extensively spread out and their filopodia were visible in the SEM pictures. WSF, which contains the tripeptide sequence Arg-Gly-Asp (believed to be a specific interaction site for cell-attachment), displayed much higher cell attachment and growth compared to DSF. The cells attached on WSF became virtually flat and their filopodia could be seen, indicating that the cells were very strongly held on the surface.

Amino Acid Sequence↗

Attachment and growth of cultured fibroblast cells on silk protein matrices.

The attachment and growth of L-929 cells on films made of Bombyx mori silk proteins--fibroin and sericin and their mixtures--was studied by a cell culture method. Both cell attachment and growth were dependent on a minimum of around 90% sericin in the mixture. The results from electron micrography as well as from the DSC measurements supported the notion that the mixture of the two proteins fibroin and sericin has a phase-separated structure in the solid state. The observed minimum of sericin in the cell attachment and growth is thought to be a result of this phase-separated structure. Films of pure component proteins (i.e., 100% fibroin or sericin) exhibited as high a cell attachment and growth as collagen, a widely used mammalian cell culture substrate. However, a morphological study of the attached cells revealed that the cells attached to silk fibroin were extended and had a spindle shape, just like the cells attached to collagen, while the cells attached to the silk sericin had a different shape. It is concluded, therefore, that the attachment condition on silk fibroin is ideal for the viability, growth and function of the cells.

Amino Acids↗

Murine epidermal Langerhans cells express CD48, which is a counter-receptor for mouse CD2.

It has recently been demonstrated that CD48, which is expressed on T cells, B cells, thymocytes and splenocytes, is a ligand for mouse CD2 and that it can function as one of the costimulatory molecules in the activation of T cells. In this study, we examined the expression of CD48 on epidermal Langerhans cells (LC), which are potent antigen-presenting cells in the skin. Both freshly isolated and short-term-cultured LC were shown to express CD48 by flow cytometry. In contrast to most of the adhesion molecules expressed on LC, CD48 expression on short-term-cultured LC did not differ significantly from that on freshly isolated LC. We also examined the contribution of CD48 to antigen presentation by LC. We stimulated the myoglobin-specific T-cell clone, TK.G4, and allogeneic splenic T cells with freshly isolated LC and cultured LC, respectively, in the presence of various concentrations of anti-CD48 monoclonal antibody (mAb). Even at the concentration of 30 micrograms/ml, however, the anti-CD48 mAb did not show any inhibitory effects on either allogeneic or antigen-specific T-cell proliferation, whereas at a concentration 10 micrograms/ml, the anti-CD48 mAb significantly suppressed the proliferation of spleen cells stimulated with phytohaemagglutinin (PHA). These findings show that LC persistently express CD48, although its direct role in antigen presentation has not yet been clarified in vitro.

Animals↗

Hydroa vacciniforme-like lymphomatoid papulosis in a Japanese child: a new subset.

An 8-year-old Japanese girl had a 9-month history of a self-healing papulovesicular eruption on her face, scalp, and neck that resembled hydroa vacciniforme (HV). Histologically, there was a dense infiltration of small lymphocytic cells and scattered large atypical cells expressing CD30. Study of gene rearrangement showed no monoclonality in the infiltrating cells. To our knowledge, this is the second case of lymphomatoid papulosis with clinical features resembling HV. However, we also found descriptions in the literature of two other Japanese children with malignant lymphoma who both initially had clinical features resembling HV. These findings suggest that these cases of HV-like disease constitute a subset of lymphomatoid papulosis that is highly likely to progress to malignant lymphoma.

Child↗

Different expression of E-cadherin by two cutaneous gamma/delta TcR+ T-cell subsets, V gamma 5- and V gamma 5+ gamma/delta TcR+ T cells.

Recently we have demonstrated that, besides V gamma 5+ gamma/delta TcR+ T cells (V gamma 5+ gamma/delta T cells), V gamma 5- gamma/delta TcR+ T cells (V gamma 5- gamma/delta T cells) are also present in murine skin. In the present study, to characterize the functional differences between these two different cutaneous gamma/delta T cells we examined the expression pattern of E-cadherin and its two integrins. After co-culturing of Ly-5+ epidermal cells and migrating cells from organ-cultured murine skin with cutaneous stromal cells, we could expand V gamma 5+ gamma/delta T cells and V gamma 5- gamma/delta T cells, respectively. Flow cytometry demonstrated that cultured V gamma 5+ gamma/delta T cells expressed E-cadherin, but V gamma 5- gamma/delta T cells did not. This difference in E-cadherin expression was also observed in freshly isolated V gamma 5+ and V gamma 5- gamma/delta T cells. On the other hand, both V gamma 5+ and V gamma 5- gamma/delta T cells expressed the alpha chain of the vitronectin receptor, but did not express the alpha 4 integrin. Of these two cutaneous gamma/delta T cells, only V gamma 5+ gamma/delta T cells adhered to murine keratinocyte cell line, PAM 212 cells. Unexpectedly, however, the adhesion of E-cadherin-expressing V gamma 5+ gamma/delta T cells to PAM 212 cells was not inhibited by anti-E-cadherin antibody, which effectively abrogated the adhesion of Langerhans cells to PAM 212 cells. These distinct phenotypic and functional characteristics in the sub-sets of cutaneous gamma/delta T cells may suggest that they reside in different locations in the skin to play different functional roles in skin immunophysiology.

Animals↗