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Biomedical subjects

Hachiro Tagami

Publications and source records attributed to Hachiro Tagami.

At least 19 recordsLinked to original sources

Decreased keratinocyte motility in skin wound on mice lacking the epidermal fatty acid binding protein gene.

Fatty acids are shown to be important in various skin functions. Fatty acid binding protein (FABP) is postulated to serve as a lipid shuttle, solubilizing hydrophobic fatty acids and delivering them to the appropriate metabolic system. Among the FABP family proteins, epidermal-type FABP (E-FABP) is solely expressed in keratinocyte but its specific role in skin is not yet fully established. We found an elevated expression of E-FABP in regenerative keratinocytes of healing wounds. However, E-FABP null mice showed no marked differences compared to wild type mice in the process of wound closure, in vivo. On the other hand, in keratinocyte culture, E-FABP gene disruption decreased the cell motility, but did not affect the cell proliferation. E-FABP deletion may be compensated for in vivo by the microenvironment comprised of various cells such as fibroblasts and endothelial cells around the wound. Our analyses suggest that the E-FABP elevation may be necessary for the activation of cell motility within regenerative epidermis during wound healing.

Animals↗

The accelerating effect of histamine on the cutaneous wound-healing process through the action of basic fibroblast growth factor.

This study revealed that the absence of histamine in histidine decarboxylase gene-knockout (HDC(-/-)) mice resulted in delayed cutaneous wound healing and that exogenously administered histamine compensated this process. With the overproduction of histamine in HDC gene-transgenic mice, the healing was accelerated compared to the HDC(+/+) mice. These results indicate that histamine positively accelerated the cutaneous wound healing. Macrophage recruitment and angiogenesis at the wound edge were specifically impaired in HDC(-/-) mice, and histamine-treated wounds in HDC(-/-) mice demonstrated increased macrophage recruitment and angiogenesis. The amount of basic fibroblast growth factor (bFGF) in protein level at the wound edge was higher in HDC(+/+) mice, especially on the 3rd and 5th day of wound healing compared to those in HDC(-/-) mice. Topically administered SU5402, a specific antagonist to fibroblast growth factor receptor-1 tyrosine kinase, to the wound surface suppressed the wound healing in HDC(+/+) mice but not in HDC(-/-) mice. Moreover, SU5402 reduced macrophage recruitment and angiogenesis in HDC(+/+) mice. From these observations, it was concluded that the accelerated wound-healing activity of histamine was mediated by the activity of bFGF, which leads to angiogenesis, and macrophage recruitment in the wound-healing process.

Angiogenesis Inhibitors↗

Necrobiotic xanthogranuloma of the nose without paraproteinemia.

We report a 65-year-old Japanese woman who presented with a nodule on the nose near the left eye. Histological examination of the totally resected lesion revealed the typical features of necrobiotic xanthogranuloma (NXG). However, her laboratory investigation revealed no paraproteinemia. We believe that the present case represents a cutaneous variant of NXG without accompaniment of paraproteinemia or any systemic involvement.

Aged↗

Atopic xerosis: employment of noninvasive biophysical instrumentation for the functional analyses of the mildly abnormal stratum corneum and for the efficacy assessment of skin care products.

The subtle dryness of the skin surrounding the lesions of atopic dermatitis (AD) is called atopic dry skin or atopic xerosis (AX). AX is more susceptible to the development of AD skin lesions under various environmental stimuli than the clinically normal skin of the people who have or have had or will have AD, which might be called normal atopic skin (NAS) that shows no functional differences as compared to the skin of normal individuals. Routine histopathologic studies of AX that involve the invasive procedures of biopsy are not so helpful in clarifying the underlying pathogenesis. Modern, noninvasive biophysical instrumentation provides rich and quantitative information about various functional aspects of skin. The stratum corneum (SC) of AX reveals not only decreased hydration but also mildly impaired barrier function demonstrable as an increase in transepidermal water loss, elevated pH values, and an increased turnover rate of the SC consisting of thick layers of smaller-sized corneocytes. These data suggest that AX is related to mildly increased epidermal proliferation as a result of the presence of subclinical cutaneous inflammation. Although AX skin does not display any impairment in the recovery of barrier function after physical skin irritation by tape-stripping, it produces a much more severe, long-lasting inflammatory response together with a delay in barrier repair after chemical irritation such as that induced by sodium lauryl sulphate. The SC of AX is biochemically characterized by reduction in the amounts of ceramides, especially ceramide I, sebum lipids, and water-soluble amino acids. None of these changes in SC functions are seen in NAS, which includes not only the normal-looking skin of AD patients long after regression of all active lesions but also of latent atopic skin such as neonates who later develop AD. This suggests that all of the observed functional as well as biochemical abnormalities of AX are a reflection of subclinical inflammation. The presence of the underlying inflammation in AX also differentiates it from senile xerosis. The mildly impaired SC functions of AX can be improved by daily repeated applications of effective moisturizers, i.e., corneotherapy, which is effective in preventing the exacerbating progression of AX to AD resulting from inadvertent scratching of the skin that facilitates the penetration of environmental allergens into the skin. The biophysical confirmation of such efficacy of moisturizers, including cosmetic bases on the mildly impaired barrier function and decreased water-holding capacity of the SC of AX, definitely substantiates the importance of skin care for the cosmetic skin problems that affect every individual in the cold and dry season ranging from late autumn to early spring.

Cosmetics↗

Cytomegalovirus infection complicating immunosuppressive therapy for dermatomyositis.

The occurrence of opportunistic infections is not rare during the treatment of connective tissue diseases, including dermatomyositis because of the patient's immunosuppression. We describe here cytomegalovirus (CMV) infection that affected two of our patients with dermatomyositis. CMV infection has not been considered to be a frequent event in dermatomyositis, and its significance for disease progression has not been sufficiently recognized. Our case reports demonstrate the importance of close monitoring of such patients and prompt initiation of appropriate therapy to manage a suspected CMV infection.

Aged↗

Development of a novel Ag-specific immunotherapy using CpG oligodeoxynucleotides in a new, unique mouse cutaneous eosinophilic inflammation model.

The number of patients with severe atopic dermatitis (AD) has been on the rise recently. We are therefore urgently in need of a treatment that can suppress Th2 cell-mediated responses in an Ag-specific fashion. Oligodeoxynucleotides (ODN)containing CpG motifs (CpG ODN) have been highlighted as immunomodulators that reduce Th2-mediated responses. To determine the effect of CpG ODN on Th2-mediated skin inflammation, we first developed a reproducible murine model of protein Ag-induced eosinophilic inflammation that is accompanied by epidermal acanthosis and increased serum IgE levels as seen in AD. In this model we found that treatment with CpG ODN during epicutaneous sensitization in previously i.p.-primed mice prevented the development of Th2-mediated responses. Furthermore, to evaluate the therapeutic effect of CpG ODN on established eosinophilic inflammation, mice were treated with a course of the immunotherapy at a skin site remote from the area of Ag application prior to the second 1-wk epicutaneous exposure to Ag. Therapeutic treatment with CpG ODN plus Ag, but not that with CpG ODN alone, could reverse the established eosinophilic inflammation. The presented results provide strong evidence for the feasibility of a novel Ag-specific immunomodulator to treat cutaneous eosinophilic inflammation such as that characteristically found in patients with severe AD.

Animals↗

Myxofibrosarcoma (myxoid malignant fibrous histiocytoma) showing cutaneous presentation: report of two cases.

Myxofibrosarcoma or myxoid malignant fibrous histiocytoma is one of the most common fibroblastic sarcomas in older patients. It is characterized by a tendency for predominantly subcutaneous, multinodular, diffusely infiltrative growth, which may extend to the overlying dermis and present as a cutaneous lesion. Histologically, it comprises a spectrum ranging from hypocellular low-grade myxoid to high-grade pleomorphic sarcoma. Because the dermal presentation usually appears relatively banal, accurate diagnosis is sometimes challenging. In this report, we present two cases of myxofibrosarcoma with dermal involvement.

Aged↗

Objective evaluation of the efficacy of daily topical applications of cosmetics bases using the hairless mouse model of atopic dermatitis.

BACKGROUND/AIMS: Dry skin (xerosis) is a characteristic change associated with atopic dermatitis (AD) and has often been treated with topical petrolatum applications despite its unfavorable feel. Recently, various therapeutically effective skin-care products with better feel have been introduced. To elucidate the mechanisms underlying the clinical effectiveness of these newer treatments, we used our recently established hairless mouse model of AD. METHODS: We produced AD-like skin lesions in hairless mice with repeated applications of 2,4,6-trinitro-1-chrolobenzene (TNCB) in acetone for 36 days as reported previously. Groups of five mice with AD-like skin were treated once daily with an emollient-type cream containing petrolatum, a moisturizer-type cream containing 10% glycerin, a solution of 0.01% dexamethasone in acetone, or were left untreated. Over the duration of these treatments, we conducted non-invasive measurements of skin surface condition with biophysical instruments and electron microscopic evaluation of the surface area size and density of rear surface villi of superficial corneocytes. We also obtained skin biopsy samples and blood samples at each time point for histopathological evaluation and to assess serum IgE levels, respectively. RESULTS: After cessation of topical TNCB applications, AD-like skin underwent spontaneous resolution with normalization of skin appearance. A similar reduction in skin fold thickness was observed in the cream-treated mice and in the untreated mouse group, whereas a significant decrease in skin thickness was observed in the dexamethasone-treated mice. Transepidermal water loss, a measure of stratum corneum barrier function, rapidly normalized in all groups, without any statistical differences noted among groups. In comparison with untreated skin, skin surface hydration markedly improved after repeated applications of the moisturizer-type cream, whereas it consistently remained low in dexamethasone-treated skin. The skin treated with emollient-type cream appeared similar to skin that received no treatment. Reduced corneocyte surface area size resulting from repeated applications of TNCB returned to control size with cream treatments, while the corneocyte surface area size became much larger following dexamethasone treatment. In addition, the density of villi on the rear surface of corneocytes decreased with application of the creams or dexamethasone. By contrast, no changes were observed in the number of leukocytes in the epidermis or in serum IgE levels among the different treatment groups. In all treatment groups, even after 32 days of treatment, reapplication of TNCB resulted in early-stage skin swelling, but only in the steroid-treated animals did this swelling show a remarkably prolonged time course. CONCLUSIONS: Our present results indicate that the efficacy of skin-care products containing no active ingredients in treating atopic xerosis can be objectively evaluated using the hairless mouse model of AD.

Administration, Cutaneous↗

Localization of IL-8 and complement components in lesional skin of psoriasis vulgaris and pustulosis palmaris et plantaris.

BACKGROUND: Munro's microabscesses are a characteristic histopathologic feature of psoriasis vulgaris; however, the pathomechanisms underlying the migration of transepidermal leukocytes (PMNs) have not been fully elucidated yet. OBJECTIVE AND METHODS: Since the lesional scale extracts contain potent chemoattractants, such as IL-8 and C5a fragments, we studied their location in the lesions of psoriasis vulgaris and PPP with immunohistochemical techniques. RESULTS: Localization of IL-8 was not detected in the subcorneal keratinocytes but was demonstrated only in the basal keratinocytes together with migrating PMNs. In contrast, the presence of a complement fragment, C3b, was observed on the cell membranes of subcorneal keratinocytes, suggesting that these were the sites of complement activation. CONCLUSION: Such distinct localization of IL-8 and complement components suggests that the intraepidermal migration of PMNs takes place first according to the concentration gradient of IL-8, and thereafter they are guided by complement components to the final destination, the subcorneal portion of the lesional skin.

Cell Movement↗