褥瘡におけるリンパ管機能障害メカニズムの解析及び褥瘡の早期診断法の確立

• Project/Area Number: 26461655
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: 糟谷 啓 浜松医科大学, 医学部附属病院, 助教 (60599421)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Discontinued (Fiscal Year 2015)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 褥瘡 / 虚血再灌流マウスモデル / 褥瘡重症度評価 / インドシアニングリーン

Outline of Annual Research Achievements

虚血再灌流障害は褥瘡の原因の一つと考えられている。しかし、虚血再灌流障害のリンパ管に関するメカニズムについては分かっていない。我々は、マウス皮膚虚血再潅流障害モデルを作成し、リンパ管の構造的、機能的な傷害につき検討した。さらに、褥瘡の早期の重症度評価法につき検討した。障害部位の免疫組織学的検討では、虚血再灌流によりリンパ管がほぼ完全に消失していた。一方で、血管は残存していた。組織障害を起こし得る活性酸素（ROS）の発生が、障害部位で観察された。培養細胞ではリンパ管内皮細胞は血管内皮細胞よりもROSに対する感受性が高いことが分かった。次に、インドシアニングリーン(ICG)を障害部位に注射し、生体蛍光イメージングを行った。ICGの排出速度はリンパ管の機能に依存する。ICGの排出速度の低下は障害の程度と比例関係にあることが分かった。このリンパ管の機能に着目した褥瘡部位での生体イメージングは褥瘡の重症度評価法として役立つことが分かった。

Research Products

• [Journal Article] TGFb/SMAD4 signalling is inhibited in tumour cells and in ltrating lymphocytes of a patient with colon cancer associated dermatomyositis. (2015)
  • Author(s): Kasuya A, Hoshino T, Aoshima M, Tatsuno K, Fujiyama T, Tokura Y.
  • Journal Title: Journal of European Academy of Dermatology and Venereology. Volume: 29 Issue: 11 Pages: 2265-7
  • DOI: 10.1111/jdv.12569
  • Peer Reviewed / Open Access
• [Journal Article] Human T-lymphotropic virus 1 (HTLV-1)-associated lichenoid dermatitis induced by CD8+ T cells in HTLV-1 carrier, HTLV-1-associated myelopathy/tropical spastic paraparesis and adult T-cell leukemia/lymphoma. (2015)
  • Author(s): Tokura Y, Ito T, Kawakami C, Sugita K, Kasuya A, Tatsuno K, Sawada Y, Nakamura M, Shimauchi T.
  • Journal Title: Journal of Dermatology. Volume: 42 Issue: 10 Pages: 967-74
  • DOI: 10.1111/1346-8138.12980
  • Peer Reviewed / Open Access
• [Journal Article] Structural and immunological effects of skin cryoablation in a mouse model. (2015)
  • Author(s): Kasuya A, Ohta I, Tokura Y.
  • Journal Title: PLoS One. Volume: 10 Issue: 3 Pages: e0123906-e0123906
  • DOI: 10.1371/journal.pone.0123906
  • Peer Reviewed / Open Access
• [Journal Article] Simultaneous reactivation of cytomegalovirus in an adult patient with varicella (2015)
  • Author(s): Kasuya A, Kaneko Y, Enomoto N, Suda T, Tokura Y
  • Journal Title: J Dermatol (Epub ahead of print) Volume: 26 Issue: 6 Pages: 658-9
  • DOI: 10.1111/1346-8138.12858
  • Peer Reviewed / Open Access
• [Journal Article] Leukoderma in patients with atopic dermatitis. (2015)
  • Author(s): Kuriyama S, Kasuya A, Fujiyama T, Tatsuno K, Sakabe J, Yamaguchi H, Ito T, Tokura Y
  • Journal Title: J Dermatol Volume: 42 Issue: 2 Pages: 215-218
  • DOI: 10.1111/1346-8138.12746
  • Peer Reviewed / Open Access
• [Journal Article] Melanocyte-specific cytotoxic T lymphocytes in patients with rhododendrol-induced leukoderma (2015)
  • Author(s): Fujiyama T, Ikeya S, Ito T, Tatsuno K, Aoshima M, Kasuya A, Sakabe J, Suzuki T, Tokura Y
  • Journal Title: J Dermatol Sci Volume: 77 Issue: 3 Pages: 190-192
  • DOI: 10.1016/j.jdermsci.2015.01.017
  • Peer Reviewed / Open Access
• [Journal Article] Biochemical, cytological, and immunological mechanisms of rhododendrol-induced leukoderma (2015)
  • Author(s): Tokura Y, Fujiyama T, Ikeya S, Tatsuno K, Aoshima M, Kasuya A, Ito T
  • Journal Title: J Dermatol Sci Volume: 77 Issue: 3 Pages: 146-149
  • DOI: 10.1016/j.jdermsci.2015.02.001
  • Peer Reviewed / Open Access
• [Journal Article] Potential application of in vivo imaging of impaired lymphatic duct to evaluate the severity of pressure ulcer in mouse model. (2015)
  • Author(s): Kasuya A, Sakabe J, Tokura Y.
  • Journal Title: Sci Rep. Volume: 25 Issue: 1 Pages: 4173-4173
  • DOI: 10.1038/srep04173
  • Peer Reviewed / Open Access
• [Journal Article] TGFβ/SMAD4 signaling is inhibited in tumor cells and infiltrating lymphocytes of a patient with colon cancerassociated dermatomyositis. (2015)
  • Author(s): Kasuya A, Hoshino T, Aoshima M, Tatsuno K, Fujiyama T, Tokura Y
  • Journal Title: J Eur Acad Dermatol Venereol (in press) Volume: (in press)
  • Peer Reviewed
• [Journal Article] Attempts to accelerate wound healing. (2014)
  • Author(s): Kauya A, Tokura Y
  • Journal Title: J Dermatol Sci Volume: 76 Issue: 3 Pages: 169-172
  • DOI: 10.1016/j.jdermsci.2014.11.001
  • Peer Reviewed
• [Journal Article] Recurrent herpes zoster on a fixed thigh site: Its possible association with lymphoma cell invasion to femoral nerve (2014)
  • Author(s): Kasuya A, Yagyu T, Tokura Y
  • Journal Title: J Dermatol Volume: 41 Issue: 9 Pages: 854-855
  • DOI: 10.1111/1346-8138.12584
  • Peer Reviewed
• [Journal Article] Successful differentiation of herpes zoster-associated erythema multiforme from generalized extension of herpes by rapid polymerase chain reaction analysis. (2014)
  • Author(s): Kasuya A, Sakabe J, Kageyama R, Ikeya S, Fujiyama T, Tokura Y
  • Journal Title: J Dermatol Volume: 41 Issue: 6 Pages: 542-544
  • DOI: 10.1111/1346-8138.12479
  • Peer Reviewed
• [Journal Article] Measurement of cutaneous lymphatic flow rates in patients with skin cancer: area extraction method (2014)
  • Author(s): Fujiwara M, Sawada M, Kasuya A, Matsushita Y, Yamada M, Fukamizu H, Magata Y, Tokura Y, Sakahara H.
  • Journal Title: The Journal of Dermatology Volume: 41 Issue: 6 Pages: 498-504
  • DOI: 10.1111/1346-8138.12506
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] リンパ管機能障害の検出による褥瘡の重症度評価 (2016)
  • Author(s): 糟谷 啓、戸倉新樹
  • Organizer: 第4回 KHK derma 研究会
  • Place of Presentation: 大津市
  • Year and Date: 2016-02-14
• [Presentation] The impact of antiviral therapy on renal function in herpes zoster patients (2015)
  • Author(s): Kasuya A, Yamaguchi H, Aoshima M, Tatsuno K, Ikeya S, Suzuki T, Kawamura T, Fujiyama T, Ito T, Tokura Y
  • Organizer: A multiple linear regression analysis of 211 cases, The 40th Annual Meeting of the Japanese Society for Investigative Dermatology
  • Place of Presentation: Okayama, Japan
  • Year and Date: 2015-12-11
  • Int'l Joint Research
• [Presentation] 皮膚科における骨粗鬆症薬の重要性について (2015)
  • Author(s): 糟谷 啓、戸倉新樹
  • Organizer: 静岡県・骨Total Care Support研究会
  • Place of Presentation: 浜松市
  • Year and Date: 2015-12-09
• [Presentation] 皮膚凍結凝固療法のマウスモデルにおける免疫学的効果 (2015)
  • Author(s): 糟谷 啓、太田 勲、戸倉茂樹
  • Organizer: 第45回日本皮膚アレルギー・接触皮膚炎学会総会・学術大会
  • Place of Presentation: 松江市
  • Year and Date: 2015-11-20
• [Presentation] Structural and Immunological Effects of Skin Cryoablation in a Mouse Model (2015)
  • Author(s): Kasuya A, Ohta I, Tokura Y
  • Organizer: 45th Annual Meeting of the European Society for Dermatological Research
  • Place of Presentation: Rotterdam, Netherland
  • Year and Date: 2015-09-09
  • Int'l Joint Research
• [Presentation] ブラジル鉤虫による皮膚爬行症を疑った1例 (2015)
  • Author(s): 佐野祐樹、糟谷 啓、戸倉茂樹
  • Organizer: 第112回日本皮膚科学会静岡地方会
  • Place of Presentation: 静岡市
  • Year and Date: 2015-06-06
• [Presentation] PCR法による帯状疱疹関連多形紅斑と帯状疱疹汎発疹の鑑別 (2015)
  • Author(s): 糟谷 啓、坂部純一、影山玲子、池谷茂樹、藤山敏晴、戸倉新樹
  • Organizer: 第114回 日本皮膚科学会総会
  • Place of Presentation: 横浜市
  • Year and Date: 2015-05-29
• [Presentation] 免疫抑制剤とリンパ腫、第114回 (2015)
  • Author(s): 糟谷 啓、橋爪秀夫、戸倉新樹
  • Organizer: 日本皮膚科学会総会
  • Place of Presentation: 横浜市
  • Year and Date: 2015-05-29
• [Presentation] 皮膚科における骨粗鬆症薬の重要性について (2015)
  • Author(s): 糟谷 啓、戸倉新樹
  • Organizer: 第16回 遠州皮膚科医会
  • Place of Presentation: 浜松市
  • Year and Date: 2015-04-08
• [Presentation] Clearance Efficacy of Autoantibodies in Double Filtration Plasmapheresis for Pemphigus Foliaceus (2014)
  • Author(s): Kasuya A, Tokura Y
  • Organizer: 日本研究皮膚科学会
  • Place of Presentation: 大阪
  • Year and Date: 2014-12-12 – 2014-12-14
• [Presentation] 蛍光色素により血管内皮細胞とリンパ管内皮細胞の酸化ストレスへの感受性の違いを比較した (2014)
  • Author(s): 糟谷啓、坂部純一、戸倉新樹
  • Organizer: 第36回光医学光生物学学会
  • Place of Presentation: 大阪
  • Year and Date: 2014-06-26 – 2014-06-27
• [Presentation] TIF1γ-overexpressing, highly progressive endometrial carcinoma in a patient with dermatomyositis positive for malignancy-associated anti-p155/140 autoantibody (2014)
  • Author(s): Kasuya A, Tokura Y
  • Organizer: 11th Meeting of the German-Japanese Society of Dermatology
  • Place of Presentation: Heidelberg, Germany
  • Year and Date: 2014-06-11 – 2014-06-14
• [Presentation] 子宮体癌に伴う抗TIF1γ抗体陽性の皮膚筋炎では癌組織においてTIF1γが高発現していた (2014)
  • Author(s): 糟谷啓、森木睦、龍野一樹、戸倉新樹
  • Organizer: 第113回日本皮膚科学会総会
  • Place of Presentation: 京都
  • Year and Date: 2014-05-30 – 2014-06-01