Published papers

人間の皮膚は,外的要因から体内を守り,恒常性を保つ重要な役割を担う器官であるが,一方で美容的な観点からも皮膚の状態評価が重要である.皮膚の評価項目の一つとして,皮膚のシワ・キメと呼ばれる肌の細かい凸凹の形状パターンから皮膚の状態を評価するが,皮膚画像からシワ・キメは判別しづらく,シワ・キメを正確に可視化することは困難である.そこで,ダーモカメラで撮影された通常の画像(「非偏光画像」),および偏光板を用いて直接反射光成分を除いた画像(「偏光画像」)の二枚の画像を用いたシワ・キメを可視化する画像処理手法を開発した.非偏光画像および偏光画像の差分特徴量を抽出し,皮膚の色による背景輝度のムラを削減することで正確なシワ・キメの可視化を行う.さらに,シワ・キメの可視化画像についてのGabor特徴量を解析することで,シワ・キメの間隔や方向性などのパターンを定性的および定量的に評価した.(著者抄録)

Introduction: Studies have highlighted the role of actin cables in embryonic scarless wound healing across various species. However, evidence for similar structures in adult animals remains lacking. Adult newts, known for their exceptional skin regeneration capabilities, are considered promising models for postnatal human studies. This study investigated actin fiber formation and alignment during re-epithelialization in the Japanese fire-bellied newt (Cynops pyrrhogaster). Methods: Full-thickness skin excisions were performed, and actin structures were analyzed using immunohistochemistry and electron microscopy. The role of actin in re-epithelialization was assessed by inhibiting its formation with cytochalasin B. Myosin, an interacting cytoskeletal molecule, was examined through immunohistochemistry, while E-cadherin, an adhesion molecule, was analyzed using both immunohistochemistry and electron microscopy. Results: Rather than an actin cable a mesh-like actin structure, termed the “actin mesh,” was identified via immunohistochemical analysis. The actin mesh developed alongside wound epidermis extension and disappeared following complete re-epithelialization. Inhibition of actin formation delayed re-epithelialization, although the overall healing process showed no significant difference from the control group. Immunohistochemistry revealed the presence of myosin II and E-cadherin alongside Filamentous actin. Electron microscopy further demonstrated actin-rich structures in the wound epidermis compared to normal skin and confirmed E-cadherin-mediated cell-cell adhesion in the wound area. Conclusions: The actin mesh plays a critical role in facilitating rapid re-epithelialization in adult newts, presenting a valuable model for studying scarless wound healing in adult organisms. The involvement of interacting molecules such as myosin and E-cadherin provides insights into the underlying mechanisms of this process. This model offers potential applications for addressing intractable wounds in humans.

In surgical and cosmetic studies, scarless regeneration is an ideal method to heal skin wounds. To study the technologies that enable scarless skin wound healing in medicine, animal models are useful. However, four-limbed vertebrates, including humans, generally lose their competency of scarless regeneration as they transit to their terrestrial life-stages through metamorphosis, hatching or birth. Therefore, animals that serve as a model for postnatal humans must be an exception to this rule, such as the newt. Here, we evaluated the adult newt in detail for the first time. Using a Japanese fire-bellied newt, Cynops pyrrhogaster, we excised the full-thickness skin at various locations on the body, and surveyed their re-epithelialization, granulation or dermal fibrosis, and recovery of texture and appendages as well as color (hue, tone and pattern) for more than two years. We found that the skin of adult newts eventually regenerated exceptionally well through unique processes of re-epithelialization and the absence of fibrotic scar formation, except for the dorsal-lateral to ventral skin whose unique color patterns never recovered. Color pattern is species-specific. Consequently, the adult C. pyrrhogaster provides an ideal model system for studies aimed at perfect skin wound healing and regeneration in postnatal humans.

Abstract Osteomas are slow-growing, benign bony tumors. Most are asymptomatic. Paranasal sinus osteoma in the pediatric population is rare; hence, there are few reports of symptomatic osteomas. The authors report the case of a giant ethmoid sinus osteoma in an 11-year-old girl who presented with diplopia and proptosis. Total excision and reconstruction of the medial orbital wall were performed via a coronal approach. The postoperative period was uneventful, the child's vision improved, and a good cosmetic result was obtained.

Skin aging caused by various endogenous and exogenous factors results in structural and functional changes to skin components. However, the role of senescent cells in skin aging has not been clarified. To elucidate the function of senescent cells in skin aging, we evaluated the effects of the glutaminase inhibitor BPTES (bis-2-(5-phenylacetamido-1, 3, 4-thiadiazol-2-yl)ethyl sulfide) on human senescent dermal fibroblasts and aged human skin. Here, primary human dermal fibroblasts (HDFs) were induced to senescence by long-term passaging, ionizing radiation, and treatment with doxorubicin, an anticancer drug. Cell viability of HDFs was assessed after BPTES treatment. A mouse/human chimeric model was created by subcutaneously transplanting whole skin grafts from aged humans into nude mice. The model was treated intraperitoneally with BPTES or vehicle for 30 days. Skin samples were collected and subjected to reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blotting, and histological analysis. BPTES selectively eliminated senescent dermal fibroblasts regardless of the method used to induce senescence; aged human skin grafts treated with BPTES exhibited increased collagen density, increased cell proliferation in the dermis, and decreased aging-related secretory phenotypes, such as matrix metalloprotease and interleukin. These effects were maintained in the grafts 1 month after termination of the treatment. In conclusion, selective removal of senescent dermal fibroblasts can improve the skin aging phenotype, indicating that BPTES may be an effective novel therapeutic agent for skin aging.

Background: Steatocystoma is a benign cystic lesion. Steatocystoma multiplex presents as multiple lesions that occur frequently on the axilla, chest and upper limbs. Cyst removal as treatment is fundamental; methods include simple excision, puncture aspiration, punch biopsy excision and CO2 laser. However, this is difficult due to the widespread lesions of steatocystoma multiplex. We have devised a new treatment approach for steatocystoma multiplex, which involves minimally invasive incisions and the use of foreign body forceps. Method: We first made an incision of approximately 1 mm with a scalpel. While extruding the contents, foreign body forceps were advanced to grasp the inner wall of the cyst capsule. The cyst wall was peeled off from its surroundings and was removed as a lump. This was repeated for each of the cysts presented. Result: The excision time per cyst was approximately 1 minute. Since no sutures were required, 20–30 excisions could be made in a single setting within 30 minutes. The wound was hardly conspicuous. Consideration: Steatocystoma multiplex often causes stress to patients in terms of aesthetics, resulting in the desire to be treated. We think that this method of using foreign body forceps on minimal incisions is an optimal surgical technique because it is simple, with short operation time and reduced patient burden.

Chronic senescence, such as aging, contributes to age-related tissue dysfunction and disease development. The accumulation of senescent fibroblasts and the senescence-associated secretory phenotype is particularly implicated in this process. Removal of senescent cells has been reported to prevent tissue dysfunction and to extend the life span during aging. ABT-263 (navitoclax), which inhibits antiapoptotic proteins, is a leading antiaging drug; however, its role in human skin aging is unclear. This study aimed to determine the rejuvenating effects of ABT-263 on aging skin using a human skin graft mouse model. We assessed the viability of ABT-263-treated skin fibroblasts after inducing senescence. Aged human skin was transplanted under the back skin of nude mice and injected intraperitoneally with the drug or control. Analysis of the skin specimens revealed that ABT-263 induced selective elimination of senescent dermal fibroblasts. Senescent human skin treated with ABT-263 exhibited a decrease in the number of senescent cells and in the expression of aging-related secretory phenotype molecules, such as matrix metalloproteinases and interleukins and an increase in collagen density. Our results indicate that selective removal of senescent skin cells with ABT-263 can improve the aging phenotype of human skin without side effects. ABT-263 is, thus, a novel potential therapeutic agent for skin aging.

Background: Cultured epidermal transplantation (JACE) is performed for giant congenital melanocytic nevus (GCMN), but there are few reports on its postoperative course and surgical content or indications. We aimed to investigate the postoperative course of GCMN patients undergoing cultured epidermal autograft transplantation and compare the outcomes between 2 nevus tissue resection methods. Methods: Twelve GCMN patients aged 0 months to 8 years and 9 months were included in this single-center case series study. Cultured epidermal autograft transplantation was performed at 19 sites of the patients' extremities and trunks, after excision of the nevus either by using an electric dermatome, which we initially used in 2017, or by curettage with a sharp spoon and use of a hydrosurgery system (Versajet), which we started performing in 2018. Univariate and multivariate analyses were performed for factors associated with postoperative hypertrophic scar formation. Results: In all cases, >90% of the grafts survived, and the dark brown color of the nevus was reduced. Average postoperative observation period was 16.5 months. Hypertrophic scar formation was observed postoperatively at 9 wound sites out of the 12 sites with GCMN removed with a dermatome and at only 1 site with GCMN removed by curettage with use of a hydrosurgery system. In the univariate and multivariate analyses, hypertrophic scar formation was associated with age at surgery. Conclusion: In cultured epidermal autograft transplantation for GCMN, nevus tissue removal at an early age by curettage with use of a hydrosurgery system can provide good results while reducing complications, including recurrence and hypertrophic scar formation.