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We would like to introduce the current published papers and research in our department. Most of the work was carried out under the supervision of Professor Ichiro Katayama who arrived in 2004. The contents listed below are limited to the Department of Dermatology, Osaka University Graduate School of Medicine. The paper and citation numbers are posted concomitantly as a reference. For the details of each study, please refer to the accomplishments of each doctor. What is the task of a dermatologist? Treat skin disorders Find and treat underlying skin diseases Maintain the health and beauty of the skin Resolve pathogeneses and intractable skin diseases and develop new diagnostic and treatment methods Engage in educational and social contribution activities for the understanding and prevention of skin diseases This slide is used in the lecture for medical students. Figure 1 was drawn by Emeritus professor Dr. Shigeharu Sano and is considered a motif of "Angiophakomatosis in the mirror" in my dogmatic interpretation (Fig. 1).
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Page 1: We would like to introduce the current published papers and research …derma.med.osaka-u.ac.jp/english/Osaka Univ English... · 2013-05-06 · We would like to introduce the current

We would like to introduce the current published papers and research in our department.

Most of the work was carried out under the supervision of Professor Ichiro Katayama

who arrived in 2004. The contents listed below are limited to the Department of

Dermatology, Osaka University Graduate School of Medicine.

The paper and citation numbers are posted concomitantly as a reference. For the details

of each study, please refer to the accomplishments of each doctor.

What is the task of a dermatologist?

Treat skin disorders

Find and treat underlying skin diseases

Maintain the health and beauty of the skin

Resolve pathogeneses and intractable skin diseases and develop new diagnostic and

treatment methods

Engage in educational and social contribution activities for the understanding and

prevention of skin diseases

This slide is used in the lecture for medical students. Figure 1 was drawn by Emeritus

professor Dr. Shigeharu Sano and is considered a motif of "Angiophakomatosis in the

mirror" in my dogmatic interpretation (Fig. 1).

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Fig. 1

The diseases managed by dermatologists include a wide variety of common and serious

or refractory diseases (Fig. 2).

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Fig. 2

A. Molecular skin research involved in the maintenance of skin homeostasis

The skin is maintained by sophisticated homeostatic mechanisms whose collapse can

cause various skin disorders such as allergic skin diseases and skin carcinomas.

In our laboratory, Drs. Hiroyuki Murota, Mika Terao, Saki Matsui, Saori Itoi and Arisa

Kato are engaged in related subjects (Fig. 3).

Fig. 3

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1. Skin research for homeostasis of epidermal cells

a) Regulatory factors and the autonomic function of skin component cells

Control of the production of glucocorticoid local 11βHSD1 by KC.

Terao M, Murota H, Kimura A, Kato A, Ishikawa A, Igawa K, Miyoshi E, Katayama I.

PLoS One. 2011;6(9):e25039.

This is the 1st report that 11bHSD1 regulates keratinocyte proliferation and

differentiation through the control of local glucocorticoid production. An analysis of

murine 11βHSD1 KO is now ongoing (Fig. 4).

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Fig. 4

Autocrine induction of substance P mRNA and peptide in cultured normal human

keratinocytes.

Bae S, Matsunaga Y, Tanaka Y, Katayama I.

Biochem Biophys Res Commun. 1999 Sep 24;263(2):327-33.

We first reported that epidermal keratinocytes are able to produce substance P. This

study was conducted to evaluate the following current research on itching. (Fig. 5)

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Fig. 5

Epidermal keratinocytes have been reported to produce not only neuropeptides such as

substance P, but also cortisol and catecholamines. In addition, TRPVs 1, 3 and 4, which

are ion channels for temperature sensors, are expressed in the skin. These studies

indicate that the skin can autonomously act as a brain and may lead to an exact

understanding of the pathogenesis of atopic dermatitis.

Substance P induced preprotachykinin-a mRNA, neutral endopeptidase mRNA and

substance P in cultured normal fibroblasts.

Bae SJ, Matsunaga Y, Takenaka M, Tanaka Y, Hamazaki Y, Shimizu K, Katayama I.

Int Arch Allergy Immunol. 2002 Apr;127(4):316-21.

We reported the induction mechanism of the autocrine factor substance P in both

keratinocytes and skin fibroblasts. Another group reported the presence of a similar

mechanism in mast cells. We think that substance P may be involved in scratching due

to the occurrence of itching in atopic dermatitis patients and subsequent chronic skin

changes. Dr. Murota is going to analyze the effects of the nerve growth factor Artemin

on itching.

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Sweating function study

A decreased sweating function and its inverse correlation to the level of anxiety were

found in atopic dermatitis patients. The decreased sweating function is restored by

improvements in skin condition.

Abnormal Axon Reflex-Mediated Sweating Correlates with High State of Anxiety in Atopic

Dermatitis.

Kijima A, Murota H, Matsui S, Takahashi A, Kimura A, Kitaba S, Lee JB, Katayama I.

Allergol Int. 2012 Jul 25.

This report is definitely useful to instruct patients.

Impaired sweating function in adult atopic dermatitis: results of the quantitative sudomotor

axon reflex test.

Eishi K, Lee JB, Bae SJ, Takenaka M, Katayama I.

Br J Dermatol. 2002 Oct;147(4):683-8.

Sweating associated with the axon reflex is improved by proper treatment with topical

steroids (Fig. 6).

Fig. 6

Mechanism of sweating

Acetylcholine released from nerve endings causes sweating through the actions of

muscarinic receptors on sweat glands and cholinergic nerves (Fig. 7).

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Fig. 7

What is the cause of decreased sweating in atopic dermatitis patients? (Fig. 8)

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Fig. 8

Molecular mechanism of the UV response in the skin

We found that the photosensitivity associated with Sjogren's syndrome is different from

that associated with SLE.

Photoprovocation test and immunohistochemical analysis of inducible nitric oxide synthase

expression in patients with Sjögren's syndrome associated with photosensitivity.

Tsukazaki N, Watanabe M, Shimizu K, Hamasaki Y, Katayama I.

Br J Dermatol. 2002 Dec;147(6):1102-8.

Analysis of 70 KD heat shock protein (HSP70) expression in the lesional skin of lupus

erythematosus (LE) and LE related diseases.

Ghoreishi M, Katayama I, Yokozeki H, Nishioka K.

J Dermatol. 1993 Jul;20(7):400-5.

B. Research on skin allergies and autoimmune diseases

Atopic dermatitis, severe drug-induced eruptions and occupational skin diseases are

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important with respect to the close association between medical departments and society.

Therefore, providing early development of a resolution of complex pathogeneses and

treatments is essential. Drs. Hiroyuki Murota, Shun Kitaba(moved to Kinki Central

Hospital), Yukinobu Nakagawa (while studying in the United States), Akiko Kijima,

Saki Matsui and Aya Takahashi are working on the pathological analysis and

epidemiology of atopic dermatitis. Drs. Hiroaki Azukizawa, Takaaki Hanahusa, Mayuko

Nakano are working on developing a new diagnostic tool for use in drug allergies and

the analysis of pathology. Drs. Yukako Murakami and Mayuko Nakano are engaged in

work on contact dermatitis. Drs. Mamori Tani, Akinori Yokomi, Toshifumi Yamaoka

and Saori Itoi are taking over clinics and research on psoriasis, which had been the

specialty of emeritus professor Kunihiko Yoshikawa and Professor Shigetoshi Sano at

Kochi University.

2. Comprehensive study of atopic dermatitis

b) The immune function and skin barriers in atopic dermatitis

Effects of a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor and low-density

lipoprotein on proliferation and migration of keratinocytes.

Abd El-Latif MI, Murota H, Terao M, Katayama I

Br J Dermatol. 2010Jul;163(1):128-37.

Overexpression of the suppressor of cytokine signalling 3 (SOCS3) in

severe atopic dermatitis.

Horiuchi Y, Bae SJ, Katayama I.

Clin Exp Dermatol. 2006 Jan;31(1):100-4.

Pro-inflammatory cytokine IL-1alpha potential for tissue repair in chemically and

mechanically induced injury in cultured human keratinocytes.

Horiuchi Y, Bae S, Katayama I.

J Dermatol Sci. 2004 Sep;35(3):224-6.

This paper firstly reported that IL-1α plays an important role in maintaining the barrier

function of the skin.

Tumour necrosis factor-alpha but not interferon-gamma is the main inducer of inducible

protein-10 in skin fibroblasts from patients with atopic dermatitis.

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Villagomez MT, Bae SJ, Ogawa I, Takenaka M, Katayama I.

Br J Dermatol. 2004 May;150(5):910-6.

Fibroblasts from atopic dermatitis patients maintain high reactivity and affinity to

TNF-α and abundantly produce eotaxin. This study is important with respect to

revealing one of the mechanisms underlying chronic atopic dermatitis.

Glucocorticoids augment the chemically induced production and gene expression of

interleukin-1alpha through NF-kappaB and AP-1 activation in murine epidermal cells.

Miyazaki Y, Yokozeki H, Awad S, Igawa K, MinatoharaK, Satoh T, Katayama I, Nishioka K.

J Invest Dermatol. 2000 Oct;115(4):746-52.

Glucocorticoids have two properties, proinflammation and anti-inflammation,

depending on the local concentration. This study is closely related to Dr. Terao’s data

showing that glucocorticoids derived from keratinocyte regulate the danger signals of

inflammasome.

RANTES expression in psoriatic skin, and regulation of RANTES and IL-8 production in

cultured epidermal keratinocytes by active vitamin D~ 3 (tacalcitol)

Fukuoka, Ogino, Sato, Ohta, Komoriya, Nishioka, Katayama

Br J Dermatol 1998 138:63–70

c) A study of itching: The correlation to temperature sensors and nerve regeneration

Artemin causes hypersensitivity to warm sensation, mimicking warmth-provoked pruritus in

atopic dermatitis.

Murota H, Izumi M, El-Latif MI, Nishioka M, Terao M, Tani M, Matsui S, Sano S, Katayama I.

J Allergy Clin Immunol. 2012;130(3):671-682.

Dr. Murota and colleagues revealed why itching occurs in warm conditions. Substance

P-induced artemin, a neural factor that is able to trigger itching, accumulates in the skin

of patients with atopic dermatitis.

Stress response, tachykinin, and cutaneous inflammation.

Katayama I, Bae SJ, Hamasaki Y, Igawa K, Miyazaki Y, Yokozeki H, Nishioka K.

J Investig Dermatol Symp Proc. 2001 Nov;6(1):81-6.

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Review of the stress response and allergic diseases in the skin

Crosstalk of neuroendocrine and immune factors between the central and peripheral

nervous systems (Fig. 9)

Fig. 9

Nerve growth factor (NGF) and epidermal nerve fibers in atopic dermatitis model NC/Nga

mice.

Horiuchi Y, Bae S, Katayama I.

J Dermatol Sci. 2005 Jul;39(1):56-8.

Olopatadine hydrochloride improves dermatitis score and inhibits scratch behavior in

NC/Nga mice

Hiroyuki Murota, Mostafa Abd El-latif, Tadafumi Tamura, Toru Amano, Ichiro Katayama

Int Arch Allergy Immunol 2010;153:121-132

d) An analysis of the IgE antibody-mediated immune response

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Topical glucocorticoid augments IgE-mediated passive cutaneous anaphylaxis in Balb/C

mice and mast cell deficient WBB6F1 v/v mice.

Katayama I, Igawa K, Minatohara K, Nishioka K.

Clin Exp Allergy. 1997 Dec;27(12):1477-83.

IL-4 inhibits the migration of human Langerhans cells through the downregulation of TNF

receptor II expression.

Takayama K, Yokozeki H, Ghoreishi M, Satoh T, Katayama I, Umeda T, Nishioka K.

J Invest Dermatol. 1999 Oct;113(4):541-6.

Topical vitamin D3 downregulates IgE-mediated murine biphasiccutaneous reactions.

Katayama I, Minatohara K, Yokozeki H, Nishioka K.

Int Arch Allergy Immunol. 1996 Sep;111(1):71-6.

Induction of Eczematous Skin Reaction in Experimentally induced hyperplastic Skin of

Balb/C Mice by Monoclonal Anti-DNP IgE Antibody: Possible Implications for Skin Lesion

Formation in Atopic Dermatitis.

Katayama I, Tanei R, Yokozeki H, Nishioka K, Dohi Y

Int Arch Allergy Immunol 1990;93:148–154.

The report that skin eczema can be induced by increased levels of IgE antibodies

connects with the current study.

e) Epidemiology of allergic diseases

Towards global consensus on outcome measures for atopic eczema research: results of the

HOME II meeting.

Schmitt J, Spuls P, Boers M, Thomas K, Chalmers J, Roekevisch E, Schram M, Allsopp R,

Aoki V, Apfelbacher C, Bruijnzeel-Koomen C, Bruin-Weller M, Charman C, Cohen A, Dohil M,

Flohr C, Furue M, Gieler U, Hooft L,Humphreys R, Ishii HA, Katayama I, Kouwenhoven W,

Langan S, Lewis-Jones S, Merhand S, Murota H, Murrell DF, Nankervis H, Ohya Y, Oranje A,

Otsuka H, Paul C, Rosenbluth Y, Saeki H, Schuttelaar ML, Stalder, F, Svensson A, Takaoka

R, Wahlgren CF, Weidinger S, Wollenberg A, ,Williams H.

Allergy. 2012 Jul 30. : 10.1111/j.1398-9995.2012.02874.

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It is the session report of the working group in which Professor Williams aims to

establish an international consensus to evaluate atopic dermatitis properly. Many expert

doctors around the world gather to discuss this issue once or twice a year. Although

there are different types of history, climate, social environment and lifestyle around the

world, the skin phenotype of disseminated skin eczema appears to be quite similar.

Why? When an international consensus is established, there may be an answer to this

question.

Showering reduces atopic dermatitis in elementary school students

Hiroyuki Murota, Aya Takahashi, Megumi Nishioka, Saki Matsui, Mika Terao, Shun Kitaba,

Ichiro Katayama

Eur J of Dermatol. Volume 20,410-1,

Japanese guideline for atopic dermatitis.

Katayama I, Kohno Y, Akiyama K, Ikezawa Z, Kondo N, Tamaki K, Kouro O; Japanese

Society of Allergology.

Allergol Int. 2011;60(2):205-20.

Guidelines for management of atopic dermatitis.

Saeki H, Furue M, Furukawa F, Hide M, Ohtsuki M, Katayama I, Sasaki R, Suto H,

Takehara K;

J Dermatol. 2009 ;36(10):563-77.

Japanese cedar pollen as an exacerbation factor in atopic dermatitis: results of atopy patch

testing and histological examination.

Yokozeki H, Takayama K, Katayama I, Nishioka K.

Acta Derm Venereol. 2006;86(2):148-51.

This report is a review of cedar pollen-induced dermatitis in Japan published in 1990.

Cataract and retinal detachment in patients with severe atopic dermatitis who were

withdrawn from the use of topical corticosteroid.

Taniguchi H, Ohki O, Yokozeki H, Katayama I, Tanaka A, Kiyosawa M, Nishioka K.

J Dermatol. 1999 Oct;26(10):658-65.

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Evaluation of non-steroidal ointment therapy for adult type atopic dermatitis: inquiry analysis

on clinical effect.

Katayama I, Taniguchi H, Matsunaga T, Yokozeki H, Nishioka K.

J Dermatol Sci. 1997 Jan;14(1):37-44.

This paper summarizes the results of a survey of treatment, except for topical steroids,

for atopic dermatitis.

f) Research and development of new therapeutic agents for atopic dermatitis

In vivo transfection of a cis element 'decoy' against signal transducers and activators of

transcription 6 (STAT6)-binding site ameliorates IgE-mediated late-phase reaction in an

atopic dermatitis mouse model.

Yokozeki H, Wu MH, Sumi K, Awad S, Satoh T, Katayama I, Takeda K, Akira S, Kaneda Y,

Nishioka K. Gene Ther. 2004 Dec;11(24):1753-62.

3. Studies of the immune response to drugs and chemicals in the skin

g) The pathogenesis of contact dermatitis and its regulation

Signal transducer and activator of transcription 6 is essential in the induction of contact

hypersensitivity.

Yokozeki H, Ghoreishi M, Takagawa S, Takayama K, Satoh T, Katayama I, Takeda K, Akira

S, Nishioka K.J Exp Med. 2000 Mar 20;191(6):995-1004.

A clinical trial of atopic dermatitis using a STAT6 decoy is now ongoing at the

dermatology department of Tokyo Medical and Dental University. A clinical trial of

allergic rhinitis using a STAT3 targeting agent is now ongoing at the dermatology

department of Kochi Medical School. These institutions closely collaborate with our

department in many areas (Fig. 10).

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Fig. 10

h) Study of the pathogenesis of urticaria

Effects of nonsedative antihistamines on productivity of patients with pruritic skin diseases.

Murota H, Kitaba S, Tani M, Wataya-Kaneda M, Katayama I.

Allergy. 2010 Jul;65(7):929-30.

Our initial report showing that itching in skin diseases markedly interferes with labor

productivity and learning efficiency led to the current study by the Ministry of Health,

Labour and Welfare.

i) Development of a diagnostic method for drug allergies

The predominant drug-specific T-cell population may switch from cytotoxic T cells to

regulatory T cells during the course of anticonvulsant-induced hypersensitivity.

Hanafusa T, Azukizawa H, Matsumura S, Katayama I.

J Dermatol Sci. 2012 Mar;65(3):213-9.

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There is no efficient technique to perform kinetic analyses of lymphocytes related to

drug allergies. Drs. Azukizawa and Hanafusa newly developed a FACS analysis method

incorporating BrdU and CFSE fluorescent dye. Many researchers have taken notice of

this method (Fig. 11, 12).

Fig. 11

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Fig. 12

4. Development of an animal model related to autoimmune diseases

j) Establishment of an animal model related to thymomas and chronic GVHD

Steady state migratory RelB+ langerin+ dermal dendritic cells mediate peripheral induction

of antigen‐specific CD4+ CD25+ Foxp3+ regulatory T cells

Azukizawa H, Döhler A, Kanazawa N, Nayak A, Lipp M, Malissen B, Autenrieth I, Katayama

I, Riemann M, Weih F, Berberich-Siebelt F, Lutz MB.

Eur J Immunol. 2011 May;41(5):1420-3

Diminished regulatory T cells in cutaneous lesions of thymoma-associated multi-organ

autoimmunity: a newly described paraneoplastic autoimmune disorder with fatal clinical

course.

Hanafusa T, Azukizawa H, Kitaba S, Murota H, Umegaki N, Terao M, Sano S, Nakagiri T,

Okumura M, Katayama I.

Clin Exp Immunol. 2011 ;166(2):164-70.

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5. Development of a new pathological theory and therapeutic agents for vitiligo

vulgaris

k) Immune modulation affecting the melanin production

Positive link between STAT3 activation and Th17 Cell infiltration to the lesional skin in vitiligo

vulgaris.

Tanemura A, Kotobuki Y, Itoi S, Takata T, Sano S, Katayama I.

J Dermatol Sci. 2012 Sep;67(3):207-9. Epub 2012 Jun 28.

This is the 1st report showing that STAT3 is activated in the epidermal keratinocytes of

vitiligo lesions. This finding may closely connect to the mechanism showing that

combination therapy with vitamin D3 and UV is effective for vitiligo vulgaris.

Dysregulation of melanocyte function by Th17-related cytokines: significance of Th17 cell

infiltration in autoimmune vitiligo vulgaris.

Kotobuki Y, Tanemura A, Yang L, Itoi S, Wataya-Kaneda M, Murota H, Fujimoto M, Serada

S, Naka T, Katayama I.

Pigment Cell Melanoma Res. 2012 Mar;25(2):219-30 (Fig. 13, 14)

Fig. 13

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Fig. 14

l) Development of new therapeutic and epidemiological studies of vitiligo vulgaris

(Fig. 15)

Revised classification/nomenclature of vitiligo and related issues: the Vitiligo Global Issues

Consensus Conference.

Ezzedine K, Lim HW, Suzuki T, Katayama I, Hamzavi I, Lan CC, Goh BK, Anbar T, Silva de

Castro C, Lee AY, Parsad D, van Geel N, Le Poole IC, Oiso N, Benzekri L, Spritz R,

Gauthier Y, Hann SK, Picardo M, Taieb A; on behalf of the Vitiligo Global Issue Consensus

Conference panelists.

Pigment Cell Melanoma Res. 2012 May;25(3):E1-E13.

Seven cases of vitiligo complicated by atopic dermatitis: suggestive new spectrum of

autoimmune vitiligo.

Tanemura A, Yajima T, Nakano M, Nishioka M, Itoi S, Kotobuki Y, Higashiyama M,

Katayama I.

Eur J Dermatol. 2012 Mar-Apr;22(2):279-80.

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Open trial of topical tacalcitol [1 alpha 24(OH)2D3] and solar irradiation for vitiligo vulgaris:

upregulation of c-Kit mRNA by cultured melanocytes.

Katayama I, Ashida M, Maeda A, Eishi K, Murota H, Bae SJ.

Eur J Dermatol. 2003 Jul-Aug;13(4):372-6.

This is a report showing that topical vitamin D3 is effective for vitiligo vulgaris.

Fig. 15

C. Study of collagen diseases and vascular and connective tissue-related skin disorders

This is an important research theme that has been continuously addressed by Professor

Emeritus Shigeharu Sano, and the following current doctors: Drs. Hiroyuki Murota,

Ken Igawa, Mika Terao, Yorihisa Kotobuki, Shun Kitaba, Toshifumi Yamaoka, Linri

Yung, Saki Matsui, Saori Itoi and Arisa Kato.

6. Study of systemic scleroderma

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m) Development of sequential therapeutic agents for scleroderma, Raynaud’s

phenomenon and intractable skin ulcers (Fig. 16)

Fig. 16

Periostin Facilitates Skin Sclerosis via PI3K/Akt Dependent Mechanism in a Mouse Model of

Scleroderma

Lingli Yang, Satoshi Serada, Minoru Fujimoto, Mika Terao, Yorihisa Kotobuki ,Shun Kitaba,

Saki Matsui, Akira Kudo,Tetsuji Naka, Hiroyuki Murota, Ichiro Katayama

PLoS ONE, 2012 - July | Volume 7 | Issue 7 | e41994

Blockade of interleukin-6 receptor alleviates disease in mouse model of scleroderma.

Kitaba S, Murota H, Terao M, Azukizawa H, Terabe F, Shima Y, Fujimoto M, Tanaka T, Naka

T, Kishimoto T, Katayama I.

Am J Pathol. 2012 Jan;180(1):165-76.

Anti-IL6 receptor antibodies are able to improve sclerodermas other than rheumatoid

arthritis. This paper evaluates the pathogenesis. The following clinical trial is now

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ongoing (Fig. 17).

Fig. 17

The skin of patients with systemic sclerosis softened during the treatment with anti-IL-6

receptor antibody tocilizumab

Yoshihito Shima, Yusuke Kuwahara, Hiroyuki Murota, Shun Kitaba, Mari Kawai, Toru Hirano,

Junsuke Arimitsu, Masashi Narazaki, Keisuke Hagihara, Atsushi Ogata, Ichiro Katayama,

Ichiro Kawase, Tadamitsu Kishimoto, and Toshio Tanaka

Rheumatology 2010 49: 2408-12

Tumor necrosis factor-alpha processing inhibitor-1 inhibits skin fibrosis in

bleomycin-induced murine model of scleroderma.

Terao M, Murota H, Kitaba S, Katayama I.

Exp Dermatol. 2010 Jan;19(1):38-43.

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Hepatocyte growth factor both prevents and ameliorates the symptoms of dermal sclerosis

in a mouse model of scleroderma.

Wu MH, Yokozeki H, Takagawa S, Yamamoto T, Satoh T, Kaneda Y, Katayama I, Nishioka

K.

Gene Ther. 2004 Jan;11(2):170-80.

Disruption of tumor necrosis factor receptor p55 impairs collagen turnover in experimentally

induced sclerodermic skin fibroblasts.

Murota H, Hamasaki Y, Nakashima T, Yamamoto K, Katayama I, Matsuyama T.

Arthritis Rheum. 2003 Apr;48(4):1117-25.

Animal model of sclerotic skin. I: Local injections of bleomycin induce sclerotic skin

mimicking scleroderma.

Yamamoto T, Takagawa S, Katayama I, Yamazaki K, Hamazaki Y, Shinkai H, Nishioka K.

J Invest Dermatol. 1999 Apr;112(4):456-62.

An animal model of scleroderma that we developed is now widely used worldwide.

7. The crosstalk of the connective tissue matrix

n) Regulatory mechanisms of collagen synthesis

Periostin, a matricellular protein, accelerates cutaneous wound repair by activating

dermal fibroblasts.

Ontsuka K, Kotobuki Y, Shiraishi H, Serada S, Ohta S, Tanemura A, Yang L, Fujimoto M,

Arima K, Suzuki S, Murota H, Toda S, Kudo A, Conway SJ, Narisawa Y, Katayama I,

Izuhara K, Naka T.

Exp Dermatol. 2012 May;21(5):331-336.

Emedastine difumarate inhibits histamine-induced collagen synthesis in dermal fibroblasts.

Murota H, Bae S, Hamasaki Y, Maruyama R, Katayama I.

J Investig Allergol Clin Immunol. 2008;18(4):245-52.

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Substance P augments fibrogenic cytokine-induced fibroblast proliferation: possible

involvement of neuropeptide in tissue fibrosis.

Katayama I, Nishioka K.

J Dermatol Sci. 1997 Sep;15(3):201-6.

o) Study of the molecular mechanisms of wound healing

Upregulation of N-acetylglucosaminyltransferase-V by heparin-bindingE GF-like growth

factor induces keratinocyte proliferation and epidermal hyperplasia.

Kimura A, Terao M, Kato A, Hanafusa T, Murota H, Katayama I, Miyoshi E.

Exp Dermatol. 2012 Jul;21(7):515-9.

Enhanced epithelial-mesenchymal transition-like phenotype in

N-acetylglucosaminyltransferase V transgenic mouse skin promotes wound healing.

Terao M, Ishikawa A, Nakahara S, Kimura A, Kato A, Moriwaki K, Kamada Y, Murota H,

Taniguchi N, Katayama I, Miyoshi E.

J Biol Chem. 2011 Aug 12;286(32):28303-11.

Novel research showing that a glycosyltransferase, GnT-V, modulates wound healing

through the EMT

8. Study of the mechanisms underlying erythema formation resembling annular

erythema in Sjögren's syndrome

o) A clinical evaluation of annular erythema

Annular erythema associated with Sjögren's syndrome: review of the literature on the

management and clinical analysis of skin lesions.

Katayama I, Kotobuki Y, Kiyohara E, Murota H.

Mod Rheumatol. 2010 Apr;20(2):123-9

A review of annular erythema in Sjögren's syndrome until 2008

Clinical and immunological analysis of annular erythema associated with Sjögren syndrome.

Katayama I, Yamamoto T, Otoyama K, Matsunaga T, Nishioka K.

Dermatology. 1994;189 Suppl 1:14-7.

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A review of the etiology of annular erythema in Sjogren's syndrome (Fig. 18)

Fig. 18

Annular erythema. A comparative study of Sjögren syndrome with subacute cutaneous

lupus erythematosus.

Katayama I, Teramoto N, Arai H, Nishioka K, Nishiyama S.

Int J Dermatol. 1991 Sep;30(9):635-9.

A review of the differences between SCLE (subacute cutaneous lupus erythematosus)

and annular erythema in Sjögren's syndrome

Annular erythema: a possible association with primary Sjögren's syndrome.

Teramoto N, Katayama I, Arai H, Eto H, Kamimura K, Uetsuka M, Kondo S, Nishioka K,

Nishiyama S.

J Am Acad Dermatol. 1989 Apr;20(4):596-601

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The 1st report of annular erythema in Sjögren's syndrome. This report triggered

argumentation whether annular erythema is substantially different between Sjögren's

syndrome and SLE among researchers in Europe and the United States.

9. Circulatory failure, skin ulcers and anti-phospholipid antibody syndrome

p) Ulcers and circulatory failure

New aspect of anti-inflammatory action of lipo-prostaglandinE1 in the management of

collagen diseases-related skin ulcer.

Murota H, Kotobuki Y, Umegaki N, Tani M, Katayama I.

Rheumatol Int. 2008 Sep;28(11):1127-35.

Heat-inductible turbidity precipitates in plasma samples of livedo reticularis with summer

ulceration: hypothesis for abnormal coagulation in summer.

Murota H, Muroi E, Hamasaki Y, Shimizu K, Masuzawa M, Katayama I.

Thromb Haemost. 2005 Jul;94(1):222-3.

q) Anti-phospholipid antibody syndrome

Anticardiolipin antibody in Henoch-Schönlein purpura and related vascular disorders.

Katayama I, Masuzawa M, Nishioka K, Nishiyama S.

Arch Dermatol Res. 1989;281(4):296-8.

Clinical manifestations in anticardiolipin antibody-positive patients with progressive systemic

sclerosis.

Katayama I, Otoyama K, Kondo S, Nishioka K, Nishiyama S.

J Am Acad Dermatol. 1990 Aug;23(2 Pt 1):198-201.

D. Study of skin malignancies

Malignant tumors are a disease of the skin boundary region. Effective treatment other

than resection of the tumor is observed to be less frequent.

The incidences of malignant melanoma, angiosarcoma and Paget's disease occurring

outside of the breast have increased due to the transition to an aging society. Drs.

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Atsushi Tanemura, Akinori Yokomi, Yorihisa Kotobuki, Eiji Kiyohara (while studying),

Mizuho Yamada and Megumi Nishioka et al. are currently developing new therapeutic

HVJ envelope vectors, such as WT-1 peptide therapy, and conducting basic research on

their effects. While only a few departments of Dermatology are engaged in malignant

lymphoma, Dr Tani tightly conducts clinics and clinical research for malignant

lymphoma collaborating with Hematology department.

Recently, several clinical trials of cutaneous lymphoma have been initiated and we also

present the following: take advantage of the rich case, I have been working hard to

deliver new treatments to patients.

Please join the person who is not limited to skin surgery with an interest in oncology.

10. A new treatment of cutaneous malignancy using HVJ envelope vectors.

r) Malignant melanoma

Vaccination with WT-1 (Wilms' Tumor gene-1) peptide and BCG-CWS in melanoma.

Nishioka M, Tanemura A, Nishida S, Nakano A, Tsuboi A, Oji Y, Oka Y, Azuma I, Sugiyama

H, Katayama I.

Eur J Dermatol. 2012 Mar-Apr;22(2):258-9.

The first report of immunotherapy with WT-1 peptides in the field of dermatology.

The combination of chemotherapy with HVJ-E containing Rad51 siRNA elicited diverse

anti-tumor effects and synergistically suppressed melanoma (Fig. 19).

Kiyohara E, Tamai K, Katayama I, Kaneda Y.

Gene Ther. 2011 Sep 8. doi: 10.1038/gt.2011.123.

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Fig. 19

CpG island methylator phenotype predicts progression of malignant melanoma.

Tanemura A, Terando AM, Sim MS, van Hoesel AQ, de Maat MF, Morton DL, Hoon DSB.

Clin Cancer Res. 2009 Mar 1;15(5):1801-7.

s) Angiosarcomas, breast Paget's disease and cutaneous lymphoma

Nodal lymphangiogenesis and metastasis: Role of tumor-induced lymphatic vessel

activation in extramammary Paget's disease.

Hirakawa S, Detmar M, Kerjaschki D, Nagamatsu S, Matsuo K, Tanemura A, Kamata N,

Higashikawa K, Okazaki H, Kameda K, Nishida-Fukuda H, Mori Katayama I, Hashimoto K.

Am J Pathol. 2009 Nov;175(5):2235-48.

Cutaneous angiosarcoma with thrombocytopenia.

Satoh T, Takahashi Y, Yokozeki H, Katayama I, Nishioka K.

J Am Acad Dermatol. 1999 May;40(5 Pt 2):872-6.

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11. A new therapeutic method for treating tuberous sclerosis

Tuberous sclerosis is a congenital disorder caused by mutations in the tumor suppressor

genes known as Hamrtin and Tuberin and associated with many kinds of skin eruption

and also lung, kidney, central nerve disorders. From 2012, Drs. Kaneda and Tanaka start

to prepare for a novel clinical trial by using topical agent of M-TOR inhibitor,

rapamycin supported by the Ministry of Health, Labour and Welfare.

Please join if you are interested.

t) New therapies using M-TOR inhibitors

A topical combination of rapamycin and tacrolimus for the treatment of angiofibroma due to

tuberous sclerosis complex (TSC): a pilot study of nine Japanese patients with TSC of

different disease severity.

Wataya-Kaneda M, Tanaka M, Nakamura A, Matsumoto S, Katayama I.

Br J Dermatol. 2011 Oct;165(4):912-6.

The first report of a new treatment for angiofibromas using M-TOR inhibitors

A novel application of topical rapamycin formulation, an inhibitor of mTOR, for patients with

hypomelanotic macules in tuberous sclerosis complex.

Wataya-Kaneda M, Tanaka M, Nakamura A, Matsumoto S, Katayama I.

Arch Dermatol. 2012 Jan;148(1):138-9.

The first report of a new treatment for hypopigmented macules using M-TOR inhibitors

(Fig. 20).

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Fig. 20

E. A new diagnosis and treatment for congenital skin disease genes

There are many genetic disorders with no effective treatment in dermatology.

Drs. Mari Wataya-Kaneda and Mari Tanaka, gene diagnosis and counseling Dr. Noriko

Arase et al. Endowed Professor Tamai Katsuhito, regeneration-inducing medicine,

Assistant Professor Mamoru Tani, Dr. Tomoko Umegaki (while studying in the United

States), gene therapy. Stem cell research for the purpose of regenerative medicine has

been energetically investigated by Assistant Professor Ken Igawa and Dr. Jun Harada.

12. An analysis of genetic skin diseases

u) The phenotypic analysis and diagnosis of hereditary skin diseases

Repigmentation of leukoderma in a piebald patient associated with a novel c-KIT gene

mutation, G592E, of the tyrosine kinase domain.

Arase N, Wataya-Kaneda M, Oiso N, Tanemura A, Kawada A, Suzuki T, Katayama I.

J Dermatol Sci. 2011 Nov;64(2):147-9.

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Cutaneous symptoms in a patient with cardiofaciocutaneous syndrome and increased ERK

phosphorylation in skin fibroblasts.

Terao M, Sakai N, Higashiyama S, Kotobuki Y, Tanemura A, Wataya-Kaneda M, Yutsudo M,

Ozono K, Katayama I.

Br J Dermatol. 2010 Oct;163(4):881-4.

Eosinophil infiltration in three patients with generalized atrophic benign epidermolysis

bullosa from a Japanese family: molecular genetic and immunohistochemical studies.

Nomura M, Hamasaki Y, Katayama I, Abe K, Niikawa N, Yoshiura K.

J Hum Genet. 2005;50(9):483-9.

13. Development of novel therapies for hereditary skin disorders

v) Development of a novel gene therapy for epidermolysis bullosa

PDGFRalpha-positive cells in bone marrow are mobilized by high mobility group box 1

(HMGB1) to regenerate injured epithelia.

Tamai K, Yamazaki T, Chino T, Ishii M, Otsuru S, Kikuchi Y, Iinuma S, Saga K, Nimura K,

Shimbo T, Umegaki N, Katayama I, Miyazaki J, Takeda J, McGrath JA, Uitto J, Kaneda Y.

Proc Natl Acad Sci U S A. 2011 Apr 19;108(16):6609-14.

F. Others, development of other novel therapies, case reports

14. Novel therapies and diagnostic tools

Clinical effect of tocoretinate on lichen and macular amyloidosis.

Terao M, Nishida K, Murota H, Katayama I.

J Dermatol. 2011 Feb;38(2):179-84.

Venous insufficiency in patients with necrobiosis lipoidica

Takeshi NAKAJIMA, Atsushi TANEMURA, Shigeki INU1, Ichiro KATAYAMA

J Dermatol. 2009;36(3):166-9.

Intractable wounds caused by calcific uremic arteriolopathy treated with bisphosphonates

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Hanafusa T, Yamaguchi Y, Tani M, Umegaki N, Nishimura Y, Katayama I.

J Am Acad Dermatol. 2007;57(6):1021-5.

Silicone gel sheets relieve pain and pruritus with clinical improvement of keloid: possible

target of mast cells.

Eishi K, Bae SJ, Ogawa F, Hamasaki Y, Shimizu K, Katayama I.

J Dermatolog Treat. 2003 Dec;14(4):248-52.

Anti-oxidative therapy with oral dapsone improved HCV antibody positive annular elastolytic

giant cell granuloma.

Igawa K, Maruyama R, Katayama I, Nishioka K

The Journal of Dermatology 1997, 24(5):328-3

Topical vitamin D3 (tacalcitol) for steroid‐resistant prurigo

Katayama I, Miyazaki Y, Nishioka K.

Br J Dermatol. 1996. 135: 237–240,

Oral minocycline improved keratosis follicularis squamosa (Dohi) and related disorder:

bacterial factors are possibly involved in abberant keratinization.

Katayama I, Yokozeki H, Nishioka K.,

J Dermatol. 1994 Aug;21(8):604-8.

15. Case reports

Systemic allergic contact dermatitis to palladium inlay manifesting as annular erythema.

Hanafusa T, Yoshioka E, Azukizawa H, Itoi S, Tani M, Kira M, Katayama I.

Eur J Dermatol. 2012 Jul 4

Eosinophilic pyoderma gangrenosum with pulmonary and oral lesions preceded by

eosinophilic pneumonia: Unrecognized syndromic manifestations?

Nishioka M, Tani M, Murota H, Katayama I.

Eur J Dermatol. 2011 Jul-Aug;21(4):631-2.

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Peculiar distribution of tumorous xanthomas in an adult case of erdheim-chester disease

complicated by atopic dermatitis.

Murakami Y, Wataya-Kaneda M, Terao M, Azukizawa H, Murota H, Nakata Y, Katayama I.

Case Rep Dermatol. 2011 May;3(2):107-12.

Four cases of atopic dermatitis complicated by Sjögren's syndrome: link between dry skin

and autoimmune anhidrosis.

Kitaba S, Matsui S, Iimuro E, Nishioka M, Kijima A, Umegaki N, Murota H, Katayama I.

Allergol Int. 2011 Sep;60(3):387-91

Cedar pollen aggravates atopic dermatitis in childhood monozygotic twin patients with

allergic rhino conjunctivitis.

Murakami Y, Matsui S, Kijima A, Kitaba S, Murota H, Katayama I.

Allergol Int. 2011 Sep;60(3):397-400.

A case of juvenile dermatomyositis manifesting inflammatory epidermal nevus-like skin

lesions: unrecognized cutaneous manifestation of blaschkitis?

Takahashi Y, Murota H, Tarutani M, Sano S, Okinaga T, Tominaga K, Yano T, Katayama I.

Allergol Int. 2010 Dec;59(4):425-8.

Pilomatrix carcinoma arising from pilomatricoma after 10‐year senescent period:

Immunohistochemical analysis

Nishioka M, Tanemura A, Yamanaka T, Tani M, Miura H, Asakura M, Tamai N , Katayama I.

J Dermatol 37: 735–739, 2010

Epithelioid sarcoma on the foot masquerading as an intractable wound for> 18 years

Y. Nishimura, Y. Yamaguchi, Y. Tomita, K. Hamada, A. Maeda, A. Morita, I. Katayama

Clinical Exp Dermatoll 35:263–268, 2010

A case of toxic epidermal necrolysis-like dermatitis evolving from contact dermatitis of the

hands associated with exposure to dendrimers.

Toyama T, Matsuda H, Ishida I, Tani M, Kitaba S, Sano S, Katayama I.

Contact Dermatitis. 2008 Aug;59(2):122-3. No abstract available.

And others…

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