Biomedical subjects
Publications and source records attributed to H Tagami.
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The contiguous 874.423 base pair sequence corresponding to the 50.0-68.8 min region on the genetic map of the Escherichia coli K-12 (W3110) was constructed by the determination of DNA sequences in the 50.0-57.9 min region (360 kb) and two large (100 kb in all) and five short gaps in the 57.9-68.8 min region whose sequences had been registered in the DNA databases. We analyzed its sequence features and found that this region contained at least 894 potential open reading frames (ORFs), of which 346 (38.7%) were previously reported, 158 (17.7%) were homologous to other known genes, 232 (26.0%) were identical or similar to hypothetical genes registered in databases, and the remaining 158 (17.7%) showed no significant similarity to any other genes. A homology search of the ORFs also identified several new gene clusters. Those include two clusters of fimbrial genes, a gene cluster of three genes encoding homologues of the human long chain fatty acid degradation enzyme complex in the mitochondrial membrane, a cluster of at least nine genes involved in the utilization of ethanolamine, a cluster of the secondary set of 11 hyc genes participating in the formate hydrogenlyase reaction and a cluster of five genes coding for the homologues of degradation enzymes for aromatic hydrocarbons in Pseudomonas putida. We also noted a variety of novel genes, including two ORFs, which were homologous to the putative genes encoding xanthine dehydrogenase in the fly and a protein responsible for axonal guidance and outgrowth of the rat, mouse and nematode. An isoleucine tRNA gene, designated ileY, was also newly identified at 60.0 min.
Previous studies in mice have shown that dehydroepiandrosterone (DHEA) increases the production of Th1-associated lymphokines, and of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma), by lymphocytes. However, there are no reports concerning the effect of DHEA on the production of Th2-associated lymphokines, IL-4 and IL-5, by lymphocytes in humans. We examined serum DHEA levels in patients with atopic dermatitis (AD), which is thought to be associated with a higher activity of Th2 cells than of Th1 cells. We also studied the effects of DHEA on the production of IL-4 and IL-5 by human lymphocytes. Serum DHEA concentrations in 47 adult male patients with AD aged 19-30 years were significantly lower than those of 53 age-matched healthy male controls. Preincubation of peripheral blood mononuclear cells (PBMCs) with DHEA reduced the IL-4 production by concanavalin A-stimulated PBMCs. Their IL-5 production also showed a tendency to decrease. These results suggest that DHEA may be one of the regulators of IgE synthesis and eosinophil proliferation in patients with AD and it may act by controlling IL-4, IL-5 and IL-2 production by lymphocytes.
We investigated the regulation of C3 production by human cultured epidermal keratinocytes by enzyme-linked immunosorbent assay. The results showed that IFNgamma and TNFalpha enhanced the synthesis of C3 by epidermal keratinocytes in a concentration-dependent manner. Moreover, a protein kinase C (PKC) inhibitor blocked C3 production, whereas PMA enhanced it. There was a synergistic effect between IFNgamma and TNFalpha. In experiments to investigate the role of protein tyrosine kinase (PTK) in C3 production, we found that treatment with herbimycin A, a specific inhibitor for the c-Src-related PTK, caused significant enhancement of the C3 production induced by IFNgamma or TNFalpha, suggesting that c-Src-type PTK(s) provides a negative signal to C3 production. Each competitive inhibitor of PTK, genistein or tyrphostin, substantially increased the C3 production by IFNgamma at lower concentrations, although each agent had little effect on TNFalpha-associated production of C3 at the same concentrations. The data show that pro-inflammatory cytokines IFNgamma and TNFalpha synergistically augment C3 production by epidermal keratinocytes by different pathways.
Two Japanese patients presented with histories of exercise-induced urticaria and facial angioedema, respectively. Each patient exercised by climbing steep stairs for 5 to 10 min at 22 degrees C. A 19-year-old female student with atopic dermatitis initially developed lesions of cholinergic urticaria, which became confluent on her face, trunk and extremities and were followed by discomfort of her throat. In a 34-year-old female patient, the exercise induced angioedema on the right eyelids preceded by sneezing and rhinorrhea. Plasma histamine levels were elevated in the first patient. No changes in serum levels of complement systems were observed after the exercise challenge in either patient.
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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.
We encountered a 76-year-old woman with acute myelogenous leukemia (AML) who developed Sweet's syndrome. A biopsy specimen taken from her skin lesion on the upper arm showed an infiltration of numerous neutrophils intermingled with leukemic cells. As far as we know, this is the first report of Sweet's syndrome showing a phenotypically identified leukemic cell infiltration of AML determined as M2 in the French-American-British classification.
We describe an elderly woman in whom keratoacanthoma developed from one nodule of prurigo nodularis that had been treated with cryotherapy for 3 months. Since in our case keratoacanthoma developed after treatment with liquid nitrogen for prurigo nodularis which had been constantly scratched in the past, we hypothesize that irritations of cryotherapy in addition to repeated mechanical traumas of scratching might have played a role in the formation of this tumor.
Cutaneous ossification is a rare phenomenon in collagen diseases, despite the rather frequent occurrence in these diseases of dystrophic calcinosis. We observed metaplastic woven bone formation associated with calcification in biopsy material obtained from a 49-year-old woman suffering from mixed connective tissue disease together with multiple subcutaneous indurations. This is the first case of the presence of metaplastic bone formation in a patient with mixed connective tissue disease.
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In the Japanese, melanoma most commonly involves the plantar surface. Among 61 patients with plantar melanoma, we diagnosed 50 patients as acral lentiginous melanoma (ALM), nine as nodular melanoma, and two as superficial spreading melanoma. Partial or complete loss of pigment was observed in four of the nine nodular melanoma cases and in the nodular portions of eight ALM cases. All 12 such nodular lesions were ulcerated. The clinical diagnosis of malignant melanoma was easily made in the eight patients with ALM by the characteristic pigmentary changes around the nodule. The presence of some remaining pigment was found to be helpful in making the diagnosis in two lesions of nodular melanoma which, at first, had been clinically diagnosed as eccrine poromas. One of two completely amelanotic nodular melanomas was strongly suspected to be a melanoma because there was a history of a pre-existing pigmented macule before the development of the nodule. The other one required histopathological differentiation from Merkel cell carcinoma. Based on these findings and compared with melanoma on other parts of the body, pigmentation noted in the ulcerative nodule of plantar melanoma seems to disappear easily. This causes difficulty in distinguishing it from other skin tumours.
Patients with atopic dermatitis (AD) constantly inflict mechanical damage to their skin by scratching induced by pruritus. On excoriated lesions of the cheek we found exceedingly high levels of transepidermal water loss (TEWL) as compared to those in the normal skin of healthy subjects. However, it is not clear whether the skin of patients with AD also shows an abnormally slow recovery after mechanical damage. We compared the recovery of the barrier function of the stratum corneum (SC), after its complete removal by tape stripping, in patients with AD and age-matched healthy control subjects. On the normal-looking skin of the flexor forearm, we found no difference in the recovery process of the water barrier function of the SC between the two groups. This suggests that ability to reconstruct SC barrier function after mechanical damage is not impaired in AD patients.
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.
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.
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.