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Non-Invasive Evaluation and Differential Diagnosis for Pediatric Leukoderma in a Single Institute

Journal of Cosmetics, Dermatological Sciences and Applications 2019年第4期9卷 313-320页

作者： Madoka Takafuji Atsushi Tanemura Yuma Hanaoka Noriko Arase Eiji Kiyohara Ichiro Katayama manabu fujimoto Department of Dermatology Osaka University Graduate School of Medicine Suita Japan

Background: Although vitiligo shows a similar clinical picture to other disorders in which patients exhibit depigmented spots, there are few reports on the differentiation of these conditions from each other. Purpose: We aimed to investigate the differences and similarities between vitiligo and nevus depigmentosus in children based on the clinical course and characteristics. Materials and Methods: We conducted an examination of the disease type, treatment, progress, and differentiation of 85 cases of vitiligo and nevus depigmentosus that developed before 15 years of age among patients who visited the Osaka University Department of Dermatology with a chief complaint of white patches from January 2010 to March 2017. Results: The median age at the onset of symptoms of 79 patients with vitiligo was 4.5 years and while that of 6 patients with nevus depigmentosus was 0.8 years, indicating that the onset of nevus depigmentosus occurred earlier. While vitiligo often developed in the head and neck regions, with a tendency for depigmented spots in multiple regions, nevus depigmentosus did not show this tendency in these regions. Upon performing Wood’s lamp observation in 38 cases of vitiligo, 35 cases were found to be fluorescent chalky white and in 3 cases histologically diagnosed as vitiligo, no clear fluorescent color was observed. All 6 patients diagnosed with nevus depigmentosus exhibited a non-fluorescent off-white color under a Wood’s lamp. Conclusions: This study indicates that non-invasive observation using a Wood’s lamp is useful in the differential diagnosis of pediatric leukoderma, in addition to the subsequent clinical course, such as the presence or absence of lesional repigmentation and/or enlargement.

关键词： Pediatric Leukoderma Vitiligo Nevus Depigmentosus Non-Invasive Diagnosis Wood’s Lamp

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Successful Treatment of Intra-Arterial Peplomycin Infusion for Recurrent Oral Florid Papillomatosis

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Journal of Cosmetics, Dermatological Sciences and Applications 2019年第3期9卷 223-227页

作者： Atsushi Tanemura Madoka Takafuji Yuma Hanaoka Eiji Kiyohara Mari Wataya-Kaneda manabu fujimoto Department of Dermatology Osaka University Graduate School of Medicine Suita Osaka Japan

A 56-year-old woman had noticed the erosion of oral mucosa and tongue 8 years ago. The mucosal lesions had been initially diagnosed as oral lichen planus and resistant to various treatments with prednisolone, etretinate and mizoribine and so on. One year ago, rapidly growing verrucous lesion occurred on her upper lip. Although we administered intralesional radiation therapy, the tumor recurred and new whitish lesions on the buccal mucosa and hard palate occurred 9 months after treatment. We confirmed an anatomical blood supply to the tumors by a fluorescent real-time imaging system and subsequently administered the intra-arterial infusion of peplomycin through retrograde catheters from bilateral superficial temporal arteries under the final diagnosis as oral florid papillomatosis (OFP). The tumors were dramatically shrunk and did not recur 16 months after treatment. OFP is known as clinically multiple whitish and verrucous lesions over the oral cavity and lip and a subtype of SCC with high differentiation. We suppose that an intra-arterial infusion therapy of peplomycin should be considered as the curative treatment for OFP.

关键词： Oral Florid Papillomatosis Selective Intra-Arterial Infusion Peplomycin Sulfate

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Clinical Observation and Proposed Classification of Vitiliginous Patches by a Wood’s Lamp

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Journal of Cosmetics, Dermatological Sciences and Applications 2020年第4期10卷 204-211页

作者： Yuka Kimura Atsushi Tanemura Yukiho Kurosaki Madoka Takafuji Kazunori Yokoi Eiji Kiyohara Noriko Arase manabu fujimoto Department of Dermatology Osaka University Graduate School of Medicine Suita Japan

Although vitiligo lesion especially in static state is characterized as sharply demarcated and complete depigmented macule, we encounter patients who have various manners of hypopigmented lesions. We examined the 81 lesions using the newly released Wood’s lamp (Woody®) and investigated whether or not vitiliginous lesions could be uniformly classified under Wood’s lamp illumination and also this classification helped to estimate the tendency of repigmentation after treatment. As result, the vitiliginous lesions were categorized into 4 types on intra- and peri-lesions prior to treatment by using the Wood’s lamp. The inside and border of the lesions were classified as follows: clear white, faint, multi-dot, and perifollicular for the inside, and sharp, blunt, confetti, and trichrome for the border. Suggestive residual pigmentation was detected in 73.6% of patients at the first visit and repigmentation was observed in 67.9% of patients at least 3 months after treatment. Lesions with the “clear white” inside pattern showed significantly lower repigmentation frequency in 38.5% of patients compared to others. The borders with 4 enlarged lesions were composed of 3 of confetti-type and one of sharp-type. This preliminary study demonstrated that detailed observation with a Wood’s lamp could be the basis to classify vitiliginous lesions and might be useful for predicting not only disease progression but also repigmentation prior to treatment.

关键词： Vitiligo Wood’s Lamp Classification Repigmentation Clinical Course

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Not Follicular but Dermal Melanocyte Precursors Are Histopathologically Retained in Vitiligo

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Journal of Cosmetics, Dermatological Sciences and Applications 2023年第1期13卷 38-44页

作者： Atsushi Tanemura Ryoko Kawabe Yuka Sudo Kazunori Yokoi Takanobu Kabasawa Mitsuru Futakuchi Tamio Suzuki manabu fujimoto Department of Dermatology School of Medicine Osaka University Graduate Suita Osaka Japan Department of Pathology Faculty of Medicine Yamagata University Yamagata Japan Department of Dermatology Faculty of Medicine Yamagata University Yamagata Japan

Although perifollicular repigmentation in the vitiligo lesions is owing to activation of follicular melanocyte stem cells and/or precursor cells followed by supplying matured melanocytes, the underlying mechanism of diffuse repigmentation on the whole vitiligo surface remains still unknown. In addition to the presence of remaining melanocytes, it is conceivable that dermal melanocyte precursor cells contribute to induce diffuse repigmentation after treatment. Therefore, we investigated here whether dermal and follicular melanocyte precursor cells were reduced or not in vitiligo lesions. We performed an immunostaining for Nestin and p75NGFR as dermal melanocyte precursor cells and MITF/Fzd4 as follicular melanocyte precursor cells and compared the positive cells number between lesions and non-lesions (n = 11). Although MITF+/Fzd4+ cells in the hair follicle were significantly decreased in number in the lesions, Nestin+ and p75NGFR+ cells were not. This result indicates that dermal precursor cells could be retained in the vitiligo lesions but be disturbed to differentiate into matured melanocytes.

关键词： Melanocyte Precursor Cells p75NGFR Nestin Frizzled4 Vitiligo

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A Rare Case of Small Bowel Intussusception Due to Metastatic Malignant Melanoma

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Journal of Cosmetics, Dermatological Sciences and Applications 2019年第2期9卷 107-112页

作者： Yuma Hanaoka Atsushi Tanemura Mari Tanaka Madoka Takafuji Eiji Kiyohara Mari Wataya-Kaneda manabu fujimoto Naotsugu Haraguchi Department of Dermatology Osaka University Graduate School of Medicine Suita Osaka Japan Department of Gastroenterological Surgery Osaka University Graduate School of Medicine Suita Osaka Japan

The small intestine is sometimes metastasized by malignant melanoma. While small intestinal involvement is asymptomatic or usually nonspecific, intussusception causing intestinal obstruction is very rare. Herein we report the case of a 68-year-old man with small bowel intussusception due to metastatic malignant melanoma. Although he has been comprehensively treated with surgery, radiation, and immunotherapies, the disease rapidly progressed and consequently severe life-threatening intussusception developed on the small bowel. Because surgical resection of the obstructive melanoma lesions was successful, his quality of life was dramatically improved followed by the resumption of treatment with anti-PD-1. Several effective treatments for metastatic melanoma, including immune checkpoint inhibitors and targeted therapy, have been developed within the past decade. However, given the present case, surgical approaches to symptomatic metastatic melanoma lesions should still be considered as a treatment option for improving not only patients’ critical condition but also their survival.

关键词： Intussusception Bowel Obstruction Metastatic Melanoma Palliative Surgery Sequential Anti-Tumor Immunotherapy

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Asian Case of Metastatic Melanoma in Which a Complete Response Was Maintained after Discontinuation of Dabrafenib and Trametinib

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Journal of Cosmetics, Dermatological Sciences and Applications 2020年第2期10卷 55-58页

作者： Rikako Deno Atsushi Tanemura Madoka Takafuji Yuma Hanaoka Eiji Kiyohara Noriko Arase Mari Wataya-Kaneda manabu fujimoto Department of Dermatology Graduate School of Medicine Osaka University Suita Osaka Japan

A 54-year-old man diagnosed with metastatic melanoma of the right inguinal node with occult primary developed liver and bone metastases. The combination of dabrafenib plus trametinib was initiated, and a complete response (CR) was achieved 24 months after starting treatment. One month later, the target therapy was discontinued at the patient’s decision, and he has remained free from progression for 21 months since discontinuation. To the extent of our knowledge, real-world data in Asian melanoma concerning the discontinuation of dabrafenib plus trametinib after achieving CR have not been published;therefore, our case is a meaningful one for considering to cease target drugs and to rescue their financial toxicity.

关键词： Metastatic Melanoma Dabrafenib Trametinib Complete Response Discontinuation

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B细胞连接蛋白的表达抑制小鼠实验性自身免疫性脑脊髓炎

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免疫学杂志 2016年第10期32卷 848-852,863页

作者：金桂花李雪藤本学张庆镐延边大学医学院免疫教研室延吉133002 日本筑波大学医学医疗系皮肤科 3058575 大连大学医学院 116622

目的研究B细胞连接蛋白BLNK(B-cell linker protein)的表达对小鼠实验性自身免疫性脑脊髓炎(experimentalautoimmune encephalomyelitis,EAE)的影响并初步探讨其可能的机制。方法 MOG35-55多肽免疫BLNK缺陷(BLNK-deficient,BLNK-/-)鼠及C57BL/6鼠制备EAE小鼠模型,观察实验动物的临床症状及中枢神经系统的病理学变化;应用ELISA方法检测血清中的MOG特异性IgG和IgM抗体水平;采用流式细胞术检测脾脏中调节性T细胞的变化;分选的脾脏B淋巴细胞采用RT-PCR技术评价B细胞所分泌的细胞因子的变化。结果 BLNK-/-鼠临床症状评分明显高于C57BL/6鼠(P0.05)。结论 BLNK的表达抑制EAE,其机制可能是通过对B细胞分泌的Th1/Th2细胞因子的调节来实现。

关键词： B细胞衔接蛋白 B细胞 EAE 细胞因子白介素-10

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B细胞衔接蛋白BANK在小鼠实验性自身免疫性脑脊髓炎中的作用

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中国免疫学杂志 2017年第12期33卷 1854-1857,1861页

作者：金桂花李红花李雪藤本.学张庆镐延边大学医学院免疫学与病原生物学教研室延吉133002 日本筑波大学医学医疗系皮肤科筑波県つくば市3058575 大连大学医学院大连116622

目的:探讨B细胞特异性衔接蛋白BANK(B cell adoptor protein with ankyrin repeats)在小鼠实验性自身免疫性脑脊髓炎(Experimental autoimmune encephalomyelitis,EAE)中的作用。方法:MOG35-55多肽免疫C57BL/6鼠和BANK缺陷(BANK-deficient,BANK-/-)鼠制备EAE模型,观察实验动物临床症状及中枢神经系统的病理学变化;提取小鼠脑组织及脾脏,经流式细胞术检测中枢神经系统及外周免疫器官中的CD4+T细胞、CD8+T细胞及调节性T细胞的变化。结果:BANK-/-鼠EAE临床症状评分明显高于C57BL/6鼠,且体重减轻明显(P<0.05);HE染色结果显示,BANK-/-鼠较C57BL/6鼠炎症感染灶明显增多。流式细胞术结果显示,相对于C57BL/6鼠BANK-/-鼠中枢神经系统中CD8+T细胞百分比明显增多,而脾脏中调节性T细胞百分比明显减少,CD4/CD8比值倒置(P<0.05)。结论:B细胞衔接蛋白BANK的表达抑制EAE炎症反应。

关键词： B细胞 B细胞衔接蛋白 BANK EAE

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咪喹莫特诱导的小鼠银屑病模型的建立

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延边大学医学学报 2014年第4期37卷 241-243页

作者：金权鑫金桂花金丹李芳芳李红花藤本学孟繁平延边大学医学院免疫学与病原生物学教研室日本筑波大学医学医疗系皮肤科

[目的]建立银屑病动物模型.[方法]将5%(质量分数)咪喹莫特(IMQ)软膏连续涂抹于小鼠背部皮肤7d,构建银屑病小鼠动物模型.对照组给予同等剂量的凡士林软膏.采用临床症状评分PASI及病理学变化进行评价,确定建立模型成功.[结果]涂抹5%(质量... 详细信息

[目的]建立银屑病动物模型.[方法]将5%(质量分数)咪喹莫特(IMQ)软膏连续涂抹于小鼠背部皮肤7d,构建银屑病小鼠动物模型.对照组给予同等剂量的凡士林软膏.采用临床症状评分PASI及病理学变化进行评价,确定建立模型成功.[结果]涂抹5%(质量分数)IMQ软膏的小鼠皮肤出现红斑、鳞屑,皮肤明显变厚.HE染色结果可见,颗粒层明显减少或消失,角化不全,表皮皮肤向下延伸呈钉突状;真皮可见毛细血管扩张充血,炎性细胞浸润.[结论]IMQ诱导的银屑病小鼠模型再现了人类银屑病的典型临床症状及病理特征,是研究银屑病可行的动物模型.

关键词：银屑病咪喹莫特动物模型小鼠

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The effect of the 18R-LPSO phase on the fatigue behavior of extruded Mg/LPSO two-phase alloy through a comparative experimental-numerical study

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Journal of Magnesium and Alloys 2021年第1期9卷 130-143页

作者： Fabien Briffod Takayuki Shiraiwa manabu Enoki Department of Materials Engineering The University of Tokyo7-3-1 HongoBunkyo-kuTokyo 113-8656Japan

The fatigue behavior of four extruded Mg-Y-Zn alloys containing different volume fractions of long-period stacking ordered(LPSO)grains was investigated through a comparative study combining experiments and crystal plasticity finite element *** controlled low-cycle fatigue experiments were conducted at different strain amplitudes and revealed a limited cyclic hardening in Mg_(89)Zn_(4)Y_(7)alloy or softening in Mg_(99.2)Zn_(0.2)Y_(0.6)and Mg_(97)Zn_(1)Y_(2)alloys.A decrease in the fatigue life against the plastic strain with the increase in LPSO phase volume fraction was observed and was related the limited ductility of extruded LPSO ***-strain hysteresis curves were used to calibrate and validate a crystal plasticity model taking into account twinning and *** interaction of the different phases on the distribution of local micro-mechanical fields at the grain scale was then analyzed on synthetic microstructures under strain-controlled *** twinning activity was predicted in coarse unrecrystallized grains and tended to disappear with the increase in the LPSO phase volume ***-like facets observed in LPSO grains were related to high tensile stress,especially at the Mg/LPSO interface,due to the limited number of deformation mechanisms in LPSO crystal to accommodate out-of-basal plane *** increase of the fatigue limit with the increase in LPSO phase volume fraction was finally associated with the decreasing presence of coarse unrecrystallizedα-Mg grains due to a higher dynamic recrystallization activity during the extrusion process.

关键词： Magnesium alloy Fatigue Long-period stacking ordered phase Crystal plasticity Finite element method

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