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Regenerative medicine products using allogeneic cells, such as allogeneic cultured epidermis (allo-CE), have become a more critical therapeutic method for the treatment of burns. However, there are no clinically available allo-CE products in Japan. Therefore, establishing a quality-controlled cell bank is mandatory to create regenerative medical products using allogeneic cells. In this study, we selected ten patients from the Department of Plastic Surgery of Kyoto University Hospital to become cell donors. We performed medical interviews and blood sampling for the donor to ensure virus safety. We examined the tissues and isolated cells by performing a nucleic acid test (NAT). To establish a master cell bank, quality evaluation was performed according to the International Conference of Harmonization (ICH) Q5A. Serological tests of the blood samples from the ten donors showed that two of them were ineligible. The cells registered in the cell bank were found to be compatible after virus testing was performed, and a master cell bank was constructed. Hence, we established a keratinocyte and fibroblast bank of clinically usable human cultured cells in Japan for the first time.

Introduction: Giant congenital melanocytic nevus (GCMN) is a large melanocytic nevus, and its full-thickness removal is usually difficult due to the lack of skin available for reconstruction. Curettage is an alternative approach in cases of GCMN to remove the superficial dermis above the cleavage plane with a curette in the neonatal period, and its major complications include repigmentation, retarded epithelization, and hypertrophic scar formation. In Japan, the JACE® cultured epidermal autograft (CEA) was approved and covered by public healthcare insurance for the treatment of congenital melanocytic nevus (CMN) that is difficult to treat with conventional methods in 2016. We have used CEA for wounds after curettage in the neonatal period or following ablation after the neonatal period in combination with laser therapies to reduce the above-mentioned complications. Methods: In this study, we summarized all consecutive CMN patients treated using CEA from December 2016 to April 2019 and evaluated the duration required for epithelialization, incidence of hypertrophic scar, and color change in the target nevus by comparing the L∗ values one year later between the Curettage group, the non-Curettage group with initial treatment or the subsequent group. Results: No significant differences were seen in the epithelization period or incidence of hypertrophic scars among the groups, but the color of the target nevus was improved significantly in the Curettage group (p

INTRODUCTION: Not only chronic but also some acute wounds have a risk of infection and become unhealed wounds. Silk-elastin sponge has been developed to treat chronic wounds that are susceptible to infection. Preclinical and clinical studies suggested that silk-elastin sponge is safe for humans and can promote granulation tissue formation by reducing bacterial growth in chronic wounds. The central aim of this trial is to evaluate the clinical utility and safety of silk-elastin sponge for the treatment of chronic and acute skin ulcers. METHODS: This study is a prospective, multicenter, single-arm, uncontrolled clinical trial. In this study, 20 patients with chronic ulcers and five with an acute one will be included; patients with wound infection will be excluded. Silk-elastin sponges are applied and covered with a dressing for 14days. PLANNED OUTCOMES: The primary endpoint is the frequency of patients with chronic wounds in whom the investigator confirms the formation of a healthy wound bed at 14days after the initial application of the study device. In addition, safety for acute wounds and handiness of the study device will be assessed. TRIAL REGISTRATION NUMBER: jRCT2052210072.

An ideal hydrogel for tissue engineering and regenerative therapy is cytocompatible, biocompatible, and has low-swelling characteristics. Recently, a novel low-swelling hydrogel with a homogenous structure was developed by crosslinking a recombinant peptide, modeled on human collagen type 1 (RCPhC1), with a four-arm polyethylene glycol (tetra-PEG). Here, we hypothesized that the biodegradability of the RCPhC1 hydrogel was adjustable by altering its initial polymer concentration. Three types of RCPhC1 hydrogels were prepared using the initial polymer at different concentrations, and their morphology, swelling ratio, collagenase degradability, cytocompatibility, biocompatibility, and biodegradability were compared. The results revealed a low swelling ratio. The higher the concentration of the initial polymer, the longer it took for it to be degraded by collagenase. The average cell viability ratio was over 92% when using the direct contact method, which suggests that the hydrogels have excellent cytocompatibility. No death, tumorigenesis, exposure of the implants, or skin necrosis associated with the subcutaneous implantation of the hydrogels was found in mice in vivo. Moreover, histological evaluation revealed the formation of a thin fibrous capsule, which suggests an acceptable biocompatibility. Furthermore, as hypothesized, it was confirmed that the biodegradability can be adjusted by changing the initial polymer concentration. Collectively, the ability to fine-tune the biodegradability of RCPhC1 hydrogels demonstrates their potential for use in various clinical applications.

形態: カラー図版あり, Physical characteristics: Original contains color illustrations, Accepted: 2020-06-15, 資料番号: PA2110009000

Keloids are dermal fibroproliferative tumors that arise beyond the boundary of the original wound edges and invades adjacent tissue. Keloids are characterized by the extensive production of extracellular matrix (ECM) and abnormal fibroblast proliferation. Chondroitin sulfate (CS) is one of the major structural components of cartilage and ECM. Recently, we reported the over-accumulation of CS in keloid lesions. Keloid-derived fibroblasts (KFs) and normal dermal fibroblasts (NFs) were incubated with CS. The fibroblast proliferation rate was analyzed using a tetrazolium salt colorimetric assay. The activation of the intracellular signaling pathway was analyzed by Western blotting. Wortmannin, a PI3K inhibitor, and anti-integrin antibodies were tested to investigate the mechanism of the CS-induced cell proliferation. CS strongly stimulated the proliferation of KFs, but not NFs. The analysis of the intracellular signal transduction pathway revealed that the stimulation effect of CS on KF proliferation was due to the activation of the protein kinase B (AKT) pathway and that integrin &alpha, 1 was responsible for this phenomenon. We revealed that CS probably activates the AKT pathway through integrin to induce KF proliferation. CS may be a novel clinical therapeutic target in keloids.

The objective of this study was to investigate the effects of latent TGF-β binding protein 4 (LTBP-4) on elastic fiber regeneration in three-dimensional cultures of human dermal fibroblasts (HDFs). Appropriate collagen scaffold for elastic fiber regeneration was also examined. Collagen sponges cross-linked at 120 °C and composed of small pores (25 μm on average) was favorable for elastic fiber regeneration by HDFs. Addition of LTBP-4, followed by culture for 21 days, accelerated elastic fiber accumulation within the scaffolds. Conditioned scaffolds containing either HDFs or LTBP-4-built mature elastic fibers were implanted between the dermis and the cutaneous muscle of mice. The combined use of HDFs and LTBP-4 resulted in thicker tissues containing elastic fibers. These results indicate that weakly cross-linked collagen sponges can be used as scaffolds for regenerating elastic fibers both in vitro and in vivo, and that the addition of LTBP-4 accelerates the deposition of both elastin and fibrillin-1, and increases cell proliferation. These techniques may be useful for generating cutaneous or cardiovascular tissue equivalents; furthermore, they may serve as a useful method for the three-dimensional analyses of drugs used to treat skin diseases or to examine the microstructure of elastin networks.

Keloids occur after failure of the wound healing process; inflammation persists, and various treatments are ineffective. Keloid pathogenesis is still unclear. We have previously analysed the gene expression profiles in keloid tissue and found that HtrA1 was markedly up-regulated in the keloid lesions. HtrA1 is a serine protease suggested to play a role in the pathogenesis of various diseases, including age-related macular degeneration and osteoarthritis, by modulating extracellular matrix or cell surface proteins. We analysed HtrA1 localization and its role in keloid pathogenesis. Thirty keloid patients and twelve unrelated patients were enrolled for in situ hybridization, immunohistochemical, western blot, and cell proliferation analyses. Fibroblast-like cells expressed more HtrA1 in active keloid lesions than in surrounding lesions. The proportion of HtrA1-positive cells in keloids was significantly higher than that in normal skin, and HtrA1 protein was up-regulated relative to normal skin. Silencing HtrA1 gene expression significantly suppressed cell proliferation. HtrA1 was highly expressed in keloid tissues, and the suppression of the HtrA1 gene inhibited the proliferation of keloid-derived fibroblasts. HtrA1 may promote keloid development by accelerating cell proliferation and remodelling keloid-specific extracellular matrix or cell surface molecules. HtrA1 is suggested to have an important role in keloid pathogenesis.

1) Background: Keloids occur after the failure during the wound-healing process, persist the inflammation and are refractory to various treatments. The pathogenesis of keloids is still unclear. We previously analyzed the gene expression profiles in keloid tissue using microarray and Northern blot analysis and found that HtrA1 was markedly upregulated in the keloid lesions. HtrA1 is a member of the HtrA family of serine protease, has been suggested to play a role in the pathogenesis of various diseases including age-related macular degeneration and osteoarthritis by modulating proteins in extracellular matrix or cell surface. We focused on HtrA1, analyzed the localization and the role in keloid pathogenesis. 2) Methods: Twenty seven keloid patients and seven unrelated patients were enrolled in this study. We performed in situ hybridization analysis, immunohistochemical analysis, western blot analysis and cell proliferation assay. 3) Results: First, the fibroblast-like cells expressed HtrA1 higher in the active keloid lesions than in the surrounding lesions in situ hybridization. Second, the proportion of HtrA1-positive cells in keloid was higher than that of in normal skin significantly in immunohistochemical analysis. Third, HtrA1 protein was up-regulated, relative to normal skin tissue samples in western blot analysis. Finally, silencing of HtrA1 gene expression suppressed the cell proliferation significantly. 4) Conclusion: HtrA1 was highly expressed in keloid tissues and the suppression of HtrA1 gene inhibited the proliferation of keloid-derived fibroblasts. HtrA1 may promote keloid development through accelerating cell proliferation and remodeling keloid-specific extracellular matrix or cell surface molecules. HtrA1 is suggested to have an important role in keloid pathogenesis.

Background Keloids and hypertrophic scars are characterized by excessive proliferation of fibroblasts; abnormal accumulation of extracellular matrix; and clinical findings of raised, red, itchy, and painful lesions. There are few sufficient interventions for keloids, and the development of new therapeutic agents is urgently needed. Several studies suggest that a therapeutic possibility is β-adrenergic receptor blocker treatment. Methods In this single-center case-control study, patients who had undergone cardiac device implantation 7 to 23 months earlier were identified. The implantation incision scars of the patients were deemed to be normal or abnormal depending on their redness. The cases (abnormal scars) and controls (normal scars) were compared in terms of their β-blocker use rates. Results Of the 45 eligible patients, 12 and 33 patients were cases and controls, respectively. The cases tended to be less likely to have taken blockers than the controls (25 percent versus 45.5 percent). This difference became significant when the patients whose scars were diagnosed 7 or 8 months after implantation were excluded from the analysis: the age-adjusted odds ratios of the patients who were diagnosed 8 to 23 and 9 to 23 months after implantation were 0.10 (95 percent CI, 0.00 to 0.83; p = 0.0309) and 0.11 (95 percent CI, 0.00 to 0.98; p = 0.047), respectively. Conclusions β-Blockers may be an effective alternative modality for preventing and treating keloids and hypertrophic scars. Large-scale multicenter prospective studies that use histology to diagnose scars and diagnose the postoperative scars at the most suitable period are needed to confirm the effectiveness of blockers for abnormal scars. Clinical question/level of evidence Therapeutic, III.

The Fe-deficient troilite phase of the composition range between FeS1.00and FeS1.40was investigated in terms of the phase equilibrium, the crystal structure, and the electronic states. The Fe-vacancy relaxes the Fe3-cluster in the troilite structure. The vanadium impurity closes the Fe3-clusters in face to face manner. The electronic state modification of the idealized troilite FeS by the Fe-vacancy formation and the vanadium impurity substitution are calculated by DV-Xαcluster method to discuss the deficient troilite phase.

The selection of Gale crater as the Mars Science Laboratory landing site took over five years, involved broad participation of the science community via five open workshops, and narrowed an initial >50 sites (25 by 20 km) to four finalists (Eberswalde, Gale, Holden and Mawrth) based on science and safety. Engineering constraints important to the selection included: (1) latitude (±30°) for thermal management of the rover and instruments, (2) elevation (< −1 km) for sufficient atmosphere to slow the spacecraft, (3) relief of

A large defective troilite (Fe0.9V0.1)0.82S is prepared by a sealed silica-tube method at 800oC and characterized by a powder X-ray diffraction method and using a magnetic property measurement system. The crystal structures of a defective troilite and non defective troilite are analyzed by Rietveld method. The large defect enhances the Fe-Fe pairing and suppresses the waving of Fe-chain along c-direction. The antiferromagnetic property is observed on both troilites. The spin-flip transition temperature of the large defective troilite is 9K.

Soil samples were collected between May 27 and October 28, 2005, at sites in Yurihonjo City, Akita Prefecture, Japan. Diazinon, an extensively used organophosphate insecticide, was detected in high concentrations. Recent advances in analytical techniques enabled identification of the source of the high levels of diazinon by measuring the 13C isotope ratio of diazinon. Eight diazinon products primarily used in Akita Prefecture were analyzed. The results show that the isotope ratio of the diazinon products ranged from −31.25 ± 4.07½ to −21.67 ± 2.91½, and the isotope ratio of the diazinon in the soil samples was −24.20 ± 1.23½.

Summary: Although combination therapy for keloid including postoperative radiation therapy (RT) is common, the radiation toxicity of RT in a patient with a history of collagen vascular disease has not been fully recognized. We experienced a case of an acute radiodermatitis in a patient with keloid. This patient had a chest keloid because of the bypass surgery for Takayasu’s arteritis. After we performed an excision and postoperative RT, severe radiodermatitis occurred. We speculate that the higher single dose and the use of electron beams may be related to the onset of severe acute radiodermatitis in this case. It should be kept in mind that there is a risk of exacerbation of radiation toxicity in patients with collagen vascular disease.

In area-based stereo matching, there is a problem called "boundary overreach", i.e. the recovered object boundary turns out to be wrongly located away from the real one. This is especially harmful to segmenting objects using depth information. A few approaches have been proposed to solve this problem. However, these techniques tend to degrade on smooth surfaces. That is, there seems to be a trade-off problem between recovering precise object edges and obtaining smooth surfaces. In this paper, we propose a new simple method to solve this problem. Using multiple stereo pairs and multiple windowing, our method detects the region where the boundary overreach is likely to occur (let us call it "BO region") and adopts appropriate methods for the BO and non-BO regions. Although the proposed method is quite simple, the experimental results have shown that it is very effective at recovering both sharp object edges at their correct locations and smooth object surfaces.

The ambiguity of correspondence assignment is alleviated by utilizing the state of the neighboring correspondence of the focal point (local support) in detecting the points of correspondence in stereo vision. However, in detecting the area base points of correspondence with evaluations of the correspondence using windows, specific local supports are utilized, which can interfere with the correct correspondence assignments. In this paper, a scheme for performing correspondence assignments considering local supports which coincide correctly with the surface of an object is proposed. In this scheme, the surface of the object is directly detected as a surface model, using a new proposed GA detection scheme from the stereo degree-of-correspondence space in which the degree of correspondence is expressed as three-dimensional data. As a result, correspondence assignment is performed with correct local supports by evaluating various surface models obtained by GA search from the stereo degree-of-correspondence space. In addition, the areas in which occlusions have occurred are specified by considering uniformity requirements in searching for surface models. Thus, a method for improving the areas containing occlusions utilizing multiple-camera stereo vision is proposed. In this paper, the construction of the stereo degree-of-correspondence space, the GA search scheme, and the specification and improvement of occlusions are presented and the results of simulation experiments with objects of simple shapes are presented. © 2001 Scripta Technica, Electron Comm Jpn Pt 2, 84(8): 38–48, 2001

Purpose There is no effective therapy against hormone refractory prostate cancer. This led us to evaluate the effectiveness and toxicity of cis-platinum (CDDP) and ifosfamide (IFM) combination chemotherapy in the patients with hormone-unresponsive carcinoma of the prostate. Methods Patients with hormone-unresponsive prostate cancer were scheduled to receive CDDP 70 mg/m2 intravenously on day 1 and IFM 1.2 g/m2/day intravenously on day 1 through day 5 of 28-day cycle. Results Twenty seven patients with hormone unresponsive prostate cancer were enrolled onto this trial. Of these patients, seven (26%) demonstrated a partial objective response (PR), and ten (37%) a stable disease (ST). The response duration of PR cases lasted from 6 to 49 months with a median of 16 months and the response duration of PR + ST cases lasted from 3 to 36 months with a median of 10 months. Subjective improvement was obtained in 11 patients (41%). Survival duration of all cases were 4 to 89 months with a median of 23 months and probabilities of survival at 3 years and 5 years were 36% and 24%, respectively. The toxicity of this treatment was mostly mild to moderate, anemia (96%), leukocytopenia (89%), anorexia (81%), alopecia (67%), thrombocytopenia (44%), hematuria (38%), renal dysfunction (19%) and liver dysfunction (7%) were noticed. Severe toxicity was observed in two cases, one acute renal failure and one endotoxin shock. Conclusion We conclude that CDDP and IFM combination chemotherapy was active regimen for hormone unresponsive prostate cancer.

形態: カラー図版あり, Physical characteristics: Original contains color illustrations, 資料番号: PA1710081000

Background: Keloids present as red, painful lesions causing serious functional and cosmetic problems; however, there is no consensus regarding tools for objectively evaluating keloids. To demonstrate the utility of shear wave elastography in keloids, we investigated the correlations between clinical symptoms, ultrasound shear wave velocity, and histopathological findings. Methods: Three patients with keloids containing both red hypertrophic and mature areas were evaluated using the shear wave velocity and histopathological findings. Results: The results indicate that the shear wave velocity is high in active hypertrophic areas and low in mature areas. The areas with high elastography values exhibited numerous fibrillar collagenous matrices forming a whorled pattern with hyalinized tissue on hematoxylin-eosin staining corresponding with metachromasia on toluidine blue staining. In the mature area, the collagen fibers were oriented parallel to each other without metachromasia. Conclusions: Shear wave elastography provides quantitative estimates of tissue stiffness that correlate with the clinical symptoms and histopathological findings of the keloid lesions and can be used to assess the activity of keloids.

In area-based stereo matching, there is a problem called "boundary overreach", i.e. the recovered object boundary turns out to be wrongly located away from the real one. This is especially harmful to segmenting objects using depth information. A few approaches have been proposed to solve this problem. However, these techniques tend to degrade on smooth surfaces. That is, there seems to be a trade-off problem between recovering precise object edges and obtaining smooth surfaces. In this paper, we propose a new simple method to solve this problem. Using multiple stereo pairs and multiple windowing, our method detects the region where the boundary overreach is likely to occur (let us call it "BO region") and adopts appropriate methods for the BO and non-BO regions. Although the proposed method is quite simple, the experimental results have shown that it is very effective at recovering both sharp object edges at their correct locations and smooth object surfaces.

Summary: A keloid is a benign fibroproliferative disease of unknown etiology. Although it is common among Asians, the development of keloid on the foot is rare. We experienced a case of a keloid which arose on the foot of a 4-year-old boy after the surgical release of syndactyly. He had congenital cutaneous syndactyly of the third and fourth toes. After the reconstructive operation was performed when the patient was 2 years old, the wound became hypertrophic and grew to 37 × 37 × 8 mm. After the diagnosis of keloid based on a pathological examination, the keloid was resected completely. The web was reconstructed with a planter rectangular flap, and the skin defects were covered with a full-thickness skin graft. After the operation, we administered 5 intralesional steroid injections. Finally, the keloid was diminished 2 years after the operation.