Biomedical subjects

Kotaro Yoshimura

Publications and source records attributed to Kotaro Yoshimura.

27 records · Page 2Linked to original sources

PubMed2003

Tretinoin reverses upregulation of matrix metalloproteinase-13 in human keloid-derived fibroblasts.

Keloids are skin abnormalities that are characterized by excessive deposition of collagen bundles in the dermis. Patients with keloids complain not only about their cosmetic appearance, but also about continuous itching and/or tenderness associated with chronic inflammation. Degradation of extracellular matrix (ECM) may be upregulated, associated with the expansion of keloids into circumferential skin, and high metabolic activity of keloid tissues may be due to increased matrix metalloproteinase (MMP) activity. Based on these hypotheses, we examined differences in expression of MMP-1, MMP-8, and MMP-13 between keloid-derived and normal dermal fibroblasts. Since retinoids are potent inhibitors of MMPs in the treatment of photoaged skin and cancers, we also examined whether or not tretinoin affects MMP expression of keloid-derived fibroblasts. The results of real-time polymerase chain reaction and ELISA demonstrated significant upregulation of MMP-13 and significant downregulation of MMP-1 and MMP-8 in keloid-derived fibroblasts, at both mRNA and protein levels. MMP-1 mRNA expression in the control group was significantly upregulated after the addition of tretinoin, whereas no significant change was observed in the keloid group. MMP-8 mRNA expression in the control group was significantly upregulated by tretinoin, with the peak at 12 h, while no significant change was observed in the keloid-derived fibroblasts. In contrast, the remarkably elevated MMP-13 mRNA expression in the keloid group was significantly suppressed, with the peak suppression at 12 h after addition of tretinoin, while MMP-13 mRNA expression in the control group was not significantly changed. The decrease in MMP-1 and MMP-8 may contribute to accumulation of type I and type III collagen in keloid tissues, and this mechanism may be modulated by molecular interaction with MMP-13. Tretinoin appeared to reverse the abnormal expression profile of MMPs in keloid-derived fibroblasts, such as markedly elevated expression of MMP-13, partly through inactivation of AP-1 pathway. The present results suggest that tretinoin may be clinically useful to improve the chronic inflammation seen in keloids and prevent expansion of keloid tissues into circumferential normal skin.

Adult↗

PubMed2003

Clinical trial of bleaching treatment with 10% all-trans retinol gel.

BACKGROUND: Although an aggressive use of tretinoin along with hydroquinone enables an efficient treatment of hyperpigmented skin lesions, irritant dermatitis remains to be solved. OBJECTIVE: To evaluate the efficiency and adverse effects of 10% all-trans retinol (ROL) gel for improvement of skin hyperpigmentation. METHODS: Ten-percent ROL gel was used instead of 0.1% tretinoin gel in our two-phased bleaching protocol (bleaching and healing phases); 5% hydroquinone and 7% lactic acid ointment were used along with ROL gel in the bleaching phase (2 to 6 weeks). Five-percent hydroquinone and 7% ascorbic acid ointment were used alone during the healing phase (4 to 6 weeks). Twenty-one Japanese patients with hyperpigmented lesions on the face were enrolled in this study, and 18 patients who were followed for more than 10 weeks were analyzed. RESULTS: Improvement of pigmentation was seen in 16 of 18 patients after an average treatment period of 11.3 weeks, and in 6 patients, pigmentation was almost eliminated after treatment. Erythema and scaling were seen, however, during the bleaching phase as well as the bleaching treatment with tretinoin gel. CONCLUSION: ROL can improve skin hyperpigmentation to a similar extent to tretinoin when used at high concentration, whereas it induces irritant dermatitis as well.

Adult↗

PubMed2003

Combined therapy using Q-switched ruby laser and bleaching treatment with tretinoin and hydroquinone for acquired dermal melanocytosis.

BACKGROUND AND OBJECTIVE: Acquired dermal melanocytosis (ADM; acquired bilateral nevus of Ota-like macules) is known for its recalcitrance compared with Nevus of Ota, and we assume that one of the reasons is a higher rate and degree of postinflammatory hyperpigmentation (PIH) seen after laser treatments. METHODS: Topical bleaching treatment with 0.1% tretinoin aqueous gel and 5% hydroquinone ointment containing 7% lactic acid was initially performed (4 to 6 weeks) to discharge epidermal melanin. Subsequently, Q-switched ruby (QSR) laser was irradiated to eliminate dermal pigmentation. Both steps were repeated two to three times until patient satisfaction was obtained (usually at a 2-month interval for laser sessions). This treatment was performed in 19 patients with ADM. Skin biopsy was performed in six cases at baseline, after the bleaching pretreatment, and at the end of treatment. RESULTS: All patients showed good to excellent clearing after two to three sessions of QSR laser treatments. The total treatment period ranged from 3 to 13 (mean of 8.3) months. PIH was observed in 10.5% of the cases. Histologically, epidermal hyperpigmentation was observed in all specimens and was dramatically improved by the topical bleaching pretreatment. CONCLUSION: QSR laser combined with the topical bleaching pretreatment appeared to treat ADM consistently with a low occurrence rate of PIH and lessen the number of laser sessions and total treatment period and may also be applied to any other lesions with both epidermal and dermal pigmentation.

Adolescent↗

PubMed2003

Induction of hard keratin expression in non-nail-matrical keratinocytes by nail-matrical fibroblasts through epithelial-mesenchymal interactions.

Epithelium in the nail matrix is different from that at other body sites, in terms of clinical and histological appearance. Hard keratins are exclusively expressed in the nail matrix and bed and the hair apparatus, and hard keratin is considered a differentiation marker of these sites. Whether the expression of hard keratin in non-nail-matrical keratinocytes could be induced by nail-matrical fibroblasts was examined. Skin equivalents were constructed in three ways; ventral keratinocytes (from the ventral side of the digit) were cocultured with ventral fibroblasts (group A), ventral keratinocytes were cocultured with nail-matrical fibroblasts (group B), and nail-matrical keratinocytes were cocultured with ventral fibroblasts (group C). Immunohistochemical examinations with anti-hard keratin antibody (HKN-7) revealed hard keratin expression in groups B and C. HKN-7-positive cells were distributed continuously in the entire epithelial strata or in the suprabasal layer in group B, whereas HKN-7-positive cells were distributed spottily in group C. This study indicates extrinsic hard keratin induction in non-nail-matrical keratinocytes by nail-matrical fibroblasts and suggests that non-nail-matrical epidermal grafts may be effective in the treatment of deepithelized nail injuries. In addition, it is possible that lost nails could be reconstructed with grafts of "tissue-engineered" nail equivalent.

Antibodies, Monoclonal↗

PubMed2003

Effects of subepithelial fibroblasts on epithelial differentiation in human skin and oral mucosa: heterotypically recombined organotypic culture model.

The stratified squamous epithelia differ regionally in their patterns of morphogenesis and differentiation. Although some reports suggested that the adult epithelial phenotype is an intrinsic property of the epithelium, there is increasing evidence that subepithelial connective tissue can modify the phenotypic expression of the epithelium. The aim of this study was to elucidate whether the differentiation of cutaneous and oral epithelia is influenced by underlying mesenchymal tissues. Three normal skin samples and three normal buccal mucosa samples were used for the experiments. Skin equivalents were constructed in four ways, depending on the combinations of keratinocytes (cutaneous or mucosal keratinocytes) and fibroblasts (dermal or mucosal fibroblasts), and the effects of subepithelial fibroblasts on the differentiation of oral and cutaneous keratinocytes were studied with histological examinations and immunohistochemical analyses with anti-cytokeratin (keratins 10 and 13) antibodies. For each experiment, three paired skin equivalents were constructed by using single parent keratinocyte and fibroblast sources for each group; consequently, nine (3 x 3) organotypic cultures per group were constructed and studied. The oral and cutaneous epithelial cells maintained their intrinsic keratin expression. The keratin expression patterns in oral and cutaneous epithelia of skin equivalents were generally similar to their original patterns but were partly modified exogenously by the topologically different fibroblasts. The mucosal keratinocytes were more differentiated and expressed keratin 10 when cocultured with dermal fibroblasts, and the expression patterns of keratin 13 in cutaneous keratinocytes cocultured with mucosal fibroblasts were different from those in keratinocytes cocultured with cutaneous fibroblasts. The results suggested that the epithelial phenotype and keratin expression could be extrinsically modified by mesenchymal fibroblasts. In epithelial differentiation, however, the intrinsic control by epithelial cells may still be stronger than extrinsic regulation by mesenchymal fibroblasts.

Cell Differentiation↗

PubMed2002

Elevated expression of hepatocyte and keratinocyte growth factor in cultured buccal-mucosa-derived fibroblasts compared with normal-skin-derived fibroblasts.

Oral mucosa heals faster with less scar formation than skin and a hypertrophic scar is very rare in the oral cavity, but its mechanism has not been elucidated enough. To elucidate whether or not there are differences in growth factor expression between fibroblasts derived from buccal mucosal and normal skin, we investigated the expression of hepatocyte growth factor (HGF), keratinocyte growth factor (KGF) and stem cell factor (SCF) by cultured fibroblasts. The semiquantitative RT-PCR revealed that the expression of HGF and KGF transcripts by buccal mucosal fibroblasts was significantly elevated compared with that by dermal fibroblasts. In parallel, ELISA revealed the significant increase of HGF production by buccal mucosal fibroblasts. The level of production of SCF protein did not differ significantly. Our study suggests that increased expression of HGF and KGF by buccal mucosal fibroblasts may partly be responsible for the faster wound healing with less scar formation in the oral cavity compared with normal skin.

Adolescent↗

PubMed2002

Cosmetic color improvement of the nipple-areola complex by optimal use of tretinoin and hydroquinone.

BACKGROUND: A successful treatment to improve the color of nipple-areola complex (NAC) has never been reported, although the number of women seeking the more attractively colored NAC is not small. OBJECTIVE: To determine the effectiveness of our bleaching protocol for cosmetic improvement of the NAC. METHODS: The protocol was composed of two phases: bleaching phase (4-8 weeks) and healing phase (4-6 weeks). 0.2-0.4% tretinoin aqueous gel was applied concomitantly with 5% hydroquinone, 7% lactic acid ointment for bleaching twice a day. Tretinoin was applied to the NAC with a small cotton applicator, while hydroquinone was widely applied beyond the NAC area. After obtaining sufficient improvement in NAC color, the application of tretinoin was discontinued and hydroquinone alone was continually applied in the healing phase until the reactive erythema was eliminated. Fifteen female patients were involved in this study. RESULTS: The average treatment period was 16.6 weeks. Improvement of NAC color was obtained in 12 patients (80%) by the physician's estimation, and 11 patients (73%) satisfied with their final results. The treatment was repeated after a 1-month interval of tretinoin application in 4 patients: 2 desired further improvement in color, and 2 had the second course conducted to treat the postinflammatory hyperpigmentation on the surrounding mound induced by the first course. CONCLUSION: This approach appeared to be most effective for cosmetic improvement of NAC color among treatments available so far.

Administration, Cutaneous↗

PubMed2002

The effect of two episodes of denervation and reinnervation on skeletal muscle contractile function.

Sensory or motor "baby-sitting" has been proposed as a clinical strategy to preserve muscle integrity if motion-specific axons must regenerate over a long distance to reach denervated target muscles. Denervated muscles are innervated temporarily by using axons from nearby sensory or motor nerves. After motion specific motor axons have reached the target, the baby-sitter nerve is severed and motion-specific axons are directed to the target. Although this strategy minimizes denervation time, the requisite second episode of denervation and reinnervation might be deleterious to muscle contractile function. This study was designed to test the hypothesis that two sequential episodes of skeletal muscle denervation and reinnervation result in greater force and power deficits than a single peripheral nerve injury and repair. Adult Lewis rats underwent either transection and epineurial repair or sham exposure of the left peroneal nerve. After a 4-month recovery period, the contractile properties of the extensor digitorum longus muscle of the sham exposure group (control, n = 9) and one of the nerve division and repair groups (repair group 1, n = 9) were evaluated with measurements of the maximum tetanic isometric force, peak power, and maximal sustained power. A third group of rats underwent a second cycle of nerve division and repair (repair group 2, n = 9) at this same time point. Four months postoperatively, contractile properties of the extensor digitorum longus muscles were evaluated. Maximum tetanic isometric force and peak power were significantly reduced in repair group 2 rats as compared with repair group 1 and control rats. Maximal sustained power was not significantly different between the groups. These data support our working hypothesis that skeletal muscle contractile function is adversely affected by two cycles of denervation and reinnervation as compared with a single episode of nerve division and repair.

Animals↗

PubMedDate not supplied

Anti-androgenic therapy using oral spironolactone for acne vulgaris in Asians.

BACKGROUND: Few studies have addressed anti-androgenic therapy using oral spironolactone for acne in Asians. Obtaining this race-specific information is important because Westerners and Asians respond differently to hormone therapy. This study aimed to examine the efficacy and safety of oral spironolactone used to treat acne in Asians. METHODS: Spironolactone (initial dose, 200 mg/day) was administered orally to 139 Japanese patients (116 females and 23 males) with acne. Serum laboratory data, including various hormones and electrolytes, were examined for 25 of the subjects. RESULTS: Most of the female patients who completed the 20-week regimen exhibited excellent improvement (evaluated by a photographic grading scale), although some discontinued treatment because of menstrual disturbances or other reasons. The treatment was less efficacious for the males than for the females, and because gynecomastia developed in three male patients, spironolactone treatment for males was stopped. Examination of the serum of 25 patients did not identify any toxicity associated with the treatment. Drug eruptions and edema in the lower extremities were each seen in three patients. CONCLUSION: Oral spironolactone is effective and safe for the treatment of acne in Asian females, and can be a good option for severe, recurring, and widespread types of the condition.

Acne Vulgaris↗