Animal model for dystrophic epidermolysis bullosa and acquired epidermolysis bullosa using genetically engineered mice of type VII collagen

• Project/Area Number: 20390305
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Dermatology
• Research Institution: Hirosaki University
• Principal Investigator: SAWAMURA Daisuke Hirosaki University, 大学院・医学研究科, 教授 (60196334)
• Co-Investigator(Kenkyū-buntansha): NAKANO Hajime 弘前大学, 大学院・医学研究科, 准教授 (90281922) ; MATSUZAKI Yasushi 弘前大学, 医学部附属病院, 講師 (50322946)
• Co-Investigator(Renkei-kenkyūsha): SHIMIZU Hiroshi 北海道大学, 大学医学研究科, 教授 (00146672)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000); Fiscal Year 2010: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2009: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000); Fiscal Year 2008: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
• Keywords: 表皮水疱症 / VII型ゴラーゲン / 基底膜 / 遺伝子治療 / マウスモデル / 自己免疫 / 皮膚 / 抗体 / VII型コラーゲン / 遺伝子 / 後天性表皮水疱症 / 動物モデル / 自己免疫性疾患 / ノックアウトマウス / トランスジェニックマウス

Research Abstract

Type VII collagen is a structural protein within basement membrane zone and its gene defect leads to dystrophic epidermolysis bullosa. Also generation of autoantibody against type Vii collagen causes acquired epidermolysis bullosa. Thus, type VII collagen is a major protein in the field of dermatology. The purposes of this study are to establish models of those type VII collagen related diseases and make great contributions for disclosing disease mechanisms and development of new effective treatments using genetically engineered mice. In this study we could generate model mouse of dystrophic epidermolysis which can survive for long time. However, we could not detect auto antibody against type VII collagen in the model mice for acquired epidermolysis. Furthermore, we performed mutation analysis of patients with epidermolysis bullosa.

Research Products

• [Journal Article] Hair follicle stem cells provide a functional niche for melanocyte stem cells. (2011)
  • Author(s): Tanimura S, Tadokoro Y, Inomata K, Tanaka Y, Nishie W, McMillan JR, Sawamura D, Yancey K, Shimizu H, Nishimura EK
  • Journal Title: Cell Stem Cell 8 Pages: 177-187
  • Peer Reviewed
• [Journal Article] Raf kinase inhibitor protein expression correlates with differentiation but does not affect MAP kinase pathway activity in cutaneous squamous cell carcinoma (2010)
  • Author(s): Rokunohe D, Nakano H, Akasaka E, Kimura K, Takiyoshi N, Nakajima K, AIzu T, Kaneko T, Matsuzaki Y, Tsuchida S, Sawamura D.
  • Journal Title: J Dermatol Sci 60 Pages: 199-201
  • Peer Reviewed
• [Journal Article] Relation between the expression levels of the POU transcription factors Skn-1a and Skn-1n and keratinocyte differentiation (2010)
  • Author(s): Takemoto H, Tamai K, Akasaka E, Rokunohe D, Takiyoshi N, Umegaki N, Nakajima K, Aizu T, Kaneko T, Nakano H, Sawamura D
  • Journal Title: J Dermatol Sci 60 Pages: 203-205
  • NAID: 10027841207
  • Peer Reviewed
• [Journal Article] is an early sign of blast transformation that may mimic a common skin disease : sycosis-like eruptions in chronic myelomonocytic leukemia. (2010)
  • Author(s): Takeuchi S, Akasaka E, Rokunohe D, Kayo SJ, Matsuzaki Y, Ooshima H, Nakano H, Sawamura D. Leukemia cutis
  • Journal Title: J Dermatol 37 Pages: 916-918
  • Peer Reviewed
• [Journal Article] Blockade of autoantibody-initiated tissue damage by using recombinant fab antibody fragments against pathogenic autoantigen. (2010)
  • Author(s): Wang G, Ujiie H, Shibaki A, Nishie W, Tateishi Y, Kikuchi K, Li Q, McMillan JR, Morioka H, Sawamura D, Nakamura H, Shimizu H
  • Journal Title: Am J Pathol 176 Pages: 914-925
  • Peer Reviewed
• [Journal Article] Plectin expression patterns determine two distinct subtypes of epidermolysis bullosa simplex. (2010)
  • Author(s): Natsuga K, Nishie W, Akiyama M, Nakamura H, Shinkuma S, McMillan JR, Nagasaki A, Has C, Ouchi T, Ishiko A, Hirako Y, Owaribe K, Sawamura D, Bruckner-Tuderman L, Shimizu H
  • Journal Title: Hum Mutat 31 Pages: 308-316
  • Peer Reviewed
• [Journal Article] Response of intractable skin ulcers in recessive dystrophic epidermolysis bullosa patients to an allogeneic cultured dermal substitute. (2010)
  • Author(s): Natsuga K, Sawamura D, Goto M, Homma E, Goto-Ohguchi Y, Aoyagi S, Akiyama M, Kuroyanagi Y, Shimizu H
  • Journal Title: Acta Derm Venereol 90 Pages: 165-169
  • Peer Reviewed
• [Journal Article] A novel active mouse model for bullous pemphigoid targeting humanized pathogenic antigen (2010)
  • Author(s): Ujiie H, Shibaki A, Nishie W, Sawamura D, Wang G, Tateishi Y, Li Q, Moriuchi R, Qiao H, Nakamura H, Akiyama M, Shimizu H
  • Journal Title: J Immunol 184 Pages: 2166-2174
  • Peer Reviewed
• [Journal Article] Disseminated lupus vulgaris diagnosed more than 63 years after onset due to early misdiagnosis as a port-wine stain (2010)
  • Author(s): Takeuchi S, Nakano H, Daiki R, Akasaka E, Nishizawa A, Matsuzaki Y, Sawamura D
  • Journal Title: Clin Exp Dermatol 35
  • Peer Reviewed
• [Journal Article] Overview of epidermolysis bullosa. (2010)
  • Author(s): Sawamura D, Nakano H, Matsuzaki Y.
  • Journal Title: J Dermatol 37 Pages: 214-219
  • NAID: 10027066027
  • Peer Reviewed
• [Journal Article] Linear immunoglobulin A bullous dermatosis possibly induced by mefenamic acid. (2010)
  • Author(s): Jiin K, Nakano H, Akasaka E, Rokunohe D, Minakawa S, Ishii N, Hashimoto T, Sawamura D
  • Journal Title: J Dermatol 37 Pages: 269-271
  • NAID: 10027066309
  • Peer Reviewed
• [Journal Article] Bone marrow transplantation restores epidermal basement membrane protein expression and rescues epidermolysis bullosa model mice (2010)
  • Author(s): Fujita Y, Abe R, Inokuma D, Sasaki M, Hoshina D, Natsuga K, Nishie W, McMillan JR, Nakamura H, Shimizu T, Akiyama M, Sawamura D, Shimizu H
  • Journal Title: Proc Natl Acad Sci USA. 107 Pages: 14345-14350
  • Peer Reviewed
• [Journal Article] Bone marrow transplantation restores epidermal basement membrane protein expression and rescues epidermolysis bullosa model mice. (2010)
  • Author(s): Fujita Y
  • Journal Title: Proc Natl Acad Sci Volume: 107 Pages: 14345-14350
  • Peer Reviewed
• [Journal Article] Linear immunog lobulin A bullous dermatosis possibly induced by mefenamic acid. (2010)
  • Author(s): Jin K
  • Journal Title: J Dermatol Volume: 37 Pages: 269-271
  • Peer Reviewed
• [Journal Article] Overview of epidermolysis bullosa. (2010)
  • Author(s): Sawamura D
  • Journal Title: J Dermatol Volume: 37 Pages: 214-219
  • NAID: 10027066027
  • Peer Reviewed
• [Journal Article] Disseminated lupus vulgaris diagnosed more than 63 years after onset due to early misdiagnosis as a port-wine stain. (2010)
  • Author(s): Takeuchi s
  • Journal Title: Clin Exp Dermatol Volume: 35
  • Peer Reviewed
• [Journal Article] Anovel active mouse model for bullous pemphigoid targeting humanized pathogenic antigen. (2010)
  • Author(s): Ujiie H
  • Journal Title: J Immunol Volume: 184 Pages: 2166-2174
  • Peer Reviewed
• [Journal Article] Response of intractable skin ulcers in recessive dystrophic epidermolysis bullosa patients to an allogeneic cultured dermalsubstitute (2010)
  • Author(s): Natsuga K
  • Journal Title: Acta Derm Venereol Volume: 90 Pages: 165-169
  • Peer Reviewed
• [Journal Article] Plectin expression patterns determine two distinct subtypes of epidermolysis bullosa simplex. (2010)
  • Author(s): Natsuga K
  • Journal Title: Hum Mutat Volume: 31 Pages: 308-316
  • Peer Reviewed
• [Journal Article] Blockade of autoantibody-initiated tissue damage by using recombinant fab antibody fragments against pathogenic autoantigen. (2010)
  • Author(s): Wang G
  • Journal Title: Am J Pathol Volume: 176 Pages: 914-925
  • Peer Reviewed
• [Journal Article] Leukemia cutis is an early sign of blast transformation that may mimic a common skin disease : sycosis-like eruptions in chronic Myelomonocytic leukemia. (2010)
  • Author(s): Takeuchi s
  • Journal Title: J Dermatol Volume: 37 Pages: 916-918
  • Peer Reviewed
• [Journal Article] Relation between the expression levels of the POU transcription factors Skn-la and Skn-1n and keratinocyte differentiation. (2010)
  • Author(s): Takemoto H
  • Journal Title: J Dermatol Sci Volume: 60 Pages: 203-205
  • Peer Reviewed
• [Journal Article] Raf kinase inhibitor protein expression correlates with differentiation but does not affect MAP kinase pathway activityin cuta neous squamous cell carcinoma. (2010)
  • Author(s): Rokunohe D
  • Journal Title: J Dermatol Sci Volume: 60 Pages: 199-201
  • Peer Reviewed
• [Journal Article] Hair follicle stem cells provide a functional niche for melanocyte stem cells. (2010)
  • Author(s): Tanimura S
  • Journal Title: Cell Stem Cell Volume: 8 Pages: 177-187
  • Peer Reviewed
• [Journal Article] Response of intractable skin ulcers in recessive dystrophic epidermolysis bullosa patients to an allogeneic cultured dermal substitute. (2010)
  • Author(s): Sawamura D
  • Journal Title: Acta Derm Venereol. 90 Pages: 165-169
  • Peer Reviewed
• [Journal Article] A novel active mouse model for bullous pemphigoid targeting humanized pathogenic antigen. (2010)
  • Author(s): Ujiie H, Sawamura D
  • Journal Title: J Immunol. 184 Pages: 2166-2184
  • Peer Reviewed
• [Journal Article] Plectin expression patterns determine two distinct subtypes of epidermolysis bullosa simplex. (2010)
  • Author(s): Natsuga K, Sawamura D
  • Journal Title: Hum Mutat. 31 Pages: 308-316
  • Peer Reviewed
• [Journal Article] The compound heterozygote for new/recurrent COL7A1 mutations in a Japanese patient with bullous dermolysis of the newborn. (2009)
  • Author(s): Hashikawa K, Hamada T, Ishii N, Fukuda S, Kuroki R, Nakama T, Yasumoto S, Tamai K, Nakano H, Sawamura D, Hashimoto T
  • Journal Title: J Dermatol Sci 56 Pages: 66-68
  • NAID: 10029372278
  • Peer Reviewed
• [Journal Article] A novel humanized neonatal autoimmune blistering skin disease model induced by maternally transferred antibodies. (2009)
  • Author(s): Nishie W, Sawamura D, Natsuga K, Shinkuma S, Goto M, Shibaki A, Ujiie H, Olasz E, Yancey KB, Shimizu H
  • Journal Title: J Immunol 183 Pages: 4088-4093
  • Peer Reviewed
• [Journal Article] Keratinocyte-/fibroblast-targeted rescue of Col7a1-disrupted mice and generation of an exact dystrophic epidermolysis bullosa model using a human COL7A1 mutation. (2009)
  • Author(s): Ito K, Sawamura D, Goto M, Nakamura H, Nishie W, Sakai K, Natsuga K, Shinkuma S, Shibaki A, Uitto J, Denton CP, Nakajima O, Akiyama M, Shimizu H
  • Journal Title: Am J Pathol, 175 Pages: 2508-2517
  • Peer Reviewed
• [Journal Article] Cowden syndrome : a novel mutation and overlooked glycogenic acanthosis in gingiva. (2009)
  • Author(s): Nishizawa A, Satoh T, Watanabe R, Takayama K, Nakano H, Sawamura D, Yokozeki H
  • Journal Title: Br J Dermatol 160 Pages: 1116-1118
  • Peer Reviewed
• [Journal Article] Birt-Hogg-Dube syndrome with clear-cell and oncocytic renal tumour and trichoblastoma associated with a novel FLCN mutation. (2009)
  • Author(s): Imada K, Dainichi T, Yokomizo A, Tsunoda T, Song YH, Nagasaki A, Sawamura D, Nishie W, Shimizu H, Fukagawa S, Urabe K, Furue M, Hashimoto T, Naito S
  • Journal Title: Br J Dermatol 160 Pages: 1350-1353
  • Peer Reviewed
• [Journal Article] Novel and recurrent nonsense mutation of the SLC39A4 gene in Japanese patients with acrodermatitis enteropathica. (2009)
  • Author(s): Nakano H, Nakamura Y, Kawamura T, Shibagaki N, Matsue H, Aizu T, Rokunohe D, Akasaka E, Kimura K, Nishizawa A, Umegaki N, Mitsuhashi Y, Shimada S, Sawamura D
  • Journal Title: Br J Dermatol. 161 Pages: 184-186
  • Peer Reviewed
• [Journal Article] A Japanese family with dominant pretibial dystrophic epidermolysis bullosa : Identification of a new glycine substitution in the triple-helical collagenous domain of type VII collagen. (2009)
  • Author(s): Hamada T, Fukuda S, Ishii N, Abe T, Nagata K, Koro O, Hatano Y, Nakano H, Sawamura D, Hashimoto T
  • Journal Title: J Dermatol Sci 54 Pages: 212-214
  • NAID: 10025333973
  • Peer Reviewed
• [Journal Article] A severe and refractory case of anti-p200 pemphigoid resulting in multiple skin ulcers and scar formation. (2009)
  • Author(s): Goto-Ohguchi Y, Nishie W, Akiyama M, Tateishi Y, Aoyagi S, Tsuji-Abe Y, Sawamura D, Ishii N, Hashimoto T, Shimizu H
  • Journal Title: Dermatology 218 Pages: 265-271
  • Peer Reviewed
• [Journal Article] Haber's syndrome may be a clinical entity different from Dowling-Degos disease. (2009)
  • Author(s): Nishizawa A, Nakano H, Satoh T, Takayama K, Sawamura D, Yokozeki H
  • Journal Title: Br J Dermatol 160 Pages: 215-217
  • Peer Reviewed
• [Journal Article] Chromosome 22q11.2 deletion syndrome associated with severe eczema. (2009)
  • Author(s): Minakawa S, Nakano H, Takeda H, Mizukami H, Yagihashi S, Satou T, Sawamura D
  • Journal Title: Clin Exp Dermatol 34 Pages: 410-411
  • Peer Reviewed
• [Journal Article] Novel p.M1T and recurrent p.G301S mutations in cathepsin C in a Japanese patient with Papillon-Lefevre syndrome : implications for understanding the genotype/phenotype relationship. (2009)
  • Author(s): Ochiai T, Nakano H, Rokunohe D, Akasaka E, Toyomaki Y, Mitsuhashi Y, Sawamura D
  • Journal Title: J Dermatol Sci 53 Pages: 73-75
  • NAID: 10025332173
  • Peer Reviewed
• [Journal Article] Squamous cell carcinoma arising from Darier's disease. (2009)
  • Author(s): Matsui K, Sawamura D
  • Journal Title: Clin Exp Dermatol. 34 Pages: 1015-1016
  • Peer Reviewed
• [Journal Article] Blockade of autoantibody-initiated tissue damage by using recombinantfab antibody fragments against pathogenic autoantigen. (2009)
  • Author(s): Wang G, Sawamura D
  • Journal Title: Am J Pathol. 176 Pages: 914-925
  • Peer Reviewed
• [Journal Article] Keratinocyte-/fibroblast-targeted rescue of Col7al-disrupted mice and generation of an exact dystrophic epidermolysis bullosa model using a human COL7A1 mutation. (2009)
  • Author(s): Ito K, Sawamura D
  • Journal Title: Am J Pathol. 175 Pages: 914-925
  • Peer Reviewed
• [Journal Article] Scleroedema adultorum associated with sarcoidosis. (2009)
  • Author(s): Inokuma D, Sawamura D
  • Journal Title: Clin Exp Dermatol. 34 Pages: 428-429
  • Peer Reviewed
• [Journal Article] A linear basal cell carcinoma undergoing spontaneous regression. (2009)
  • Author(s): Takiyoshi N, Sawamura D
  • Journal Title: Clin Exp Dermatol 34 Pages: 411-413
  • Peer Reviewed
• [Journal Article] A novel humanized neonatal autoimmune blistering skin disease model induced by maternally transferred antibodies. (2009)
  • Author(s): Nishie W, Sawamura D
  • Journal Title: J Immunol. 183 Pages: 962-963
  • Peer Reviewed
• [Journal Article] An eclipse in the subungual space : a diagnostic sign for a subungual epidermal cyst? (2009)
  • Author(s): Takiyoshi N, Sawamura D
  • Journal Title: Br J Dermatol. 161 Pages: 962-963
  • Peer Reviewed
• [Journal Article] (2009)
  • Author(s): 澤村大輔
  • Journal Title: からだの科学262(日本評論社) Pages: 47-50
• [Journal Article] A novel homozygous missense mutation in the fatty aldehyde dehydrogenase gene causes Sjogren-Larsson syndrome. (2008)
  • Author(s): Nakano H, Akasaka E, Rokunohe D, Yokoyama S, Toyomaki Y, Umegaki N, Mitsuhashi Y, Sawamura D
  • Journal Title: J Dermatol Sci 52 Pages: 136-138
  • NAID: 10024457607
• [Journal Article] A de novo missense mutation in the keratin 13 gene in oral white sponge nevus (2008)
  • Author(s): Nishizawa A, Nakajima R, Nakano H, Sawamura D, Takayama K, Satoh T, Yokozeki H
  • Journal Title: Br J Dermatol 159 Pages: 974-975
• [Journal Article] Vitamin D3 inhibits expression of pemphigus vulgaris antigen, desmoglein 3 : implication of partial mechanism in pharmacological effect of VD3 on skin diseases. (2008)
  • Author(s): Yamamoto C, Tamai K, Nakano H, Matsuzaki Y, Kaneko T, Sawamura D
  • Journal Title: Mol Med Rep 1 Pages: 581-583
• [Journal Article] Clinical and Genetic analysis of Fabry disease : report of 6 cases including 3 heterozygous females. (2008)
  • Author(s): Nagasaki A, Nishie W, Sato K, Oba I, Noguchi E, Akitsu H, Sawamura D, Shimizu H
  • Journal Title: J Dermatol Sci 52 Pages: 61-64
• [Journal Article] Genotype-phenotype correlation in non-Hallopeau-Siemens recessive dystrophic epidermolysis bullosa : The splice site mutation c.6216+5G>T in the COL7A1 gene results in aberrant and normal splicings. (2008)
  • Author(s): Hamada T, Fukuda S, Ishii N, Sakaguchi S, Ishikawa T, Abe T, Yasumoto S, Hashimoto T, Nakano H, Sawamura D
  • Journal Title: J Dermatol Sci 50 Pages: 147-150
  • NAID: 10024118958
• [Journal Article] Transformation-specific matrix metalloproteinases (MMP)-7 and MMP-13 are expressed by tumour cells in epidermolysis bullosa-associated squamous cell carcinomas. (2008)
  • Author(s): Kivisaari AK, Kallajoki M, Mirtti T, McGrath JA, Bauer JW, Weber F, Konigova R, Sawamura D, Sato-Matsumura KC, Shimizu H, Csikos M, Sinemus K, Beckert W, Kahari VM
  • Journal Title: Br J Dermatol 158 Pages: 778-1785
• [Journal Article] Calcineurin/NFAT-dependent regulation of 230-kDa bullous pemphigoid antigen (BPAG1) gene expression in normal human epidermal keratinocytes. (2008)
  • Author(s): Aizu T, Tamai K, Nakano H, Rokunohe D, Toyomaki Y, Uitto J, Sawamura D
  • Journal Title: J Dermatol Sci 51 Pages: 45-51
  • NAID: 10024119446
• [Journal Article] Papillon-Lefevre syndrome and malignant melanoma : a high incidence of melanoma development in Japanese palmoplanter keratoderma patients. (2008)
  • Author(s): Nakajima K, Nakano H, Takiyoshi N, Rokunohe D, Ikenaga S, Aizu T, Kaneko T, Mitsuhashi Y, Sawamura D
  • Journal Title: Dermatol 217 Pages: 58-62
• [Journal Article] Epistatic connections between microphthalmia-associated transcription factor and endothelin signaling in Waardenburg syndrome and other pigmentary disorders. (2008)
  • Author(s): Sato-Jin K, Nishimura EK, Akasaka E, Huber W, Nakano H, Miller A, Du J, Wu M, Hanada K, Sawamura D, Fisher DE, Imokawa G
  • Journal Title: FASEB J 22 Pages: 1155-1168
• [Journal Article] Identification of Skn-1n, a splice variant that is induced by high calcium concentration and specifically expressed in normal human keratinocytes. (2008)
  • Author(s): Nakajima K, Tamai K, Yamazaki T, Toyomaki Y, Nakano H, Uitto J, Sawamura D.
  • Journal Title: J Invest Dermatol 128 Pages: 1336-1339
• [Journal Article] Vitamin D3 inhibits expression of bullous pemphigoid antigen 1 through post-transcriptional mechanism without new protein synthesis. (2008)
  • Author(s): Yamamoto C, Tamai K, Nakano H, Matsuzaki Y, Kaneko T, Sawamura D
  • Journal Title: J Dermatol Sci 50 Pages: 155-158
• [Journal Article] Reduction in epidermal Langerhans cells in patients with necrolytic migratory erythema. (2008)
  • Author(s): Rokunohe D, Nakano H, Ikenaga S, Umegaki N, Kaneko T, Matsuhashi Y, Tando Y, Toyoki Y, Hakamada K, Kusumi T, Harada K, Sawamura D
  • Journal Title: J Dermatol Sci 50 Pages: 76-80
  • NAID: 10031136041
• [Journal Article] Genotype-phenotype correlation in non-Hallopeau-Siemens recessive dystrophic epidermolysis bullosa : the splice site mutation c.6216+5G > T in the COL7A1 gene results in aberrant and normal splicings (2008)
  • Author(s): Hamada T
  • Journal Title: J Dermatol Sci 50 Pages: 147-150
  • Peer Reviewed
• [Journal Article] Vitamin D(3) inhibits expression of bullous pemphigoid antigenl through post-transcriptional mechanism without new protein synthesis (2008)
  • Author(s): Yamamoto C
  • Journal Title: J Dermatol Sci 50 Pages: 155-158
  • Peer Reviewed
• [Journal Article] Transformation-specific matrix metalloproteinases (MMP)-7 and MMP-13 are expressed by tumour cells in epidermolysis bullosa-associated squamous cell carcinomas (2008)
  • Author(s): Kivisaari AK
  • Journal Title: Br J Dermatol 158 Pages: 778-785
  • Peer Reviewed
• [Journal Article] Calcineurin/NFAT-dependent regulation of 230-kDa bullous pemphigoid antigen (BPAG1) gene expression in normal human epidermal keratinocytes (2008)
  • Author(s): Aizu T
  • Journal Title: J Dermatol Sci 51 Pages: 45-51
  • Peer Reviewed
• [Journal Article] Significance of sentinel node biopsy in the management of squamous cell carcinoma arising from recessive dystrophic epidermolysis bullosa (2008)
  • Author(s): Rokunohe A
  • Journal Title: J Dermatol 35 Pages: 336-340
  • Peer Reviewed
• [Book] やさしい皮膚科学 (2009)
  • Author(s): 澤村大輔
  • Total Pages: 248
  • Publisher: 診断と治療社
• [Remarks] ホームページ等
• [Remarks]
  • URL: http://www.med.hirosaki-u.ac.jp/~derma/index.html