[History of the German-Japanese Society of Dermatology]. / Geschichte der Deutsch-Japanischen Dermatologischen Gesellschaft.

The relationships between German and Japanese dermatology are traditionally very strong. This fact led Professor Hornstein and Professor Nishiyama to organize joint meetings of dermatologists from both countries. The first meeting of the German-Japanese Society of Dermatology was held in Erlangen, Germany, following the 16th World Congress of Dermatology in 1967. Since then, meetings have been held alternating between Germany and Japan. These meetings were successfully organized by professors from both countries. In this article, I present memorable photos from these joint meetings.

Progress in thermomechanical control of steel plates and their commercialization.

The water-cooled thermomechanical control process (TMCP) is a technology for improving the strength and toughness of water-cooled steel plates, while allowing control of the microstructure, phase transformation and rolling. This review describes metallurgical aspects of the microalloying of steel, such as niobium addition, and discusses advantages of TMCP, for example, in terms of weldability, which is reduced upon alloying. Other covered topics include the development of equipment, distortions in steel plates, peripheral technologies such as steel making and casting, and theoretical modeling, as well as the history of property control in steel plate production and some early TMCP technologies. We provide some of the latest examples of applications of TMCP steel in various industries such as shipbuilding, offshore structures, building construction, bridges, pipelines, penstocks and cryogenic tanks. This review also introduces high heat-affected-zone toughness technologies, wherein the microstructure of steel is improved by the addition of fine particles of magnesium-containing sulfides and magnesium- or calcium-containing oxides. We demonstrate that thanks to ongoing developments TMCP has the potential to meet the ever-increasing demands of steel plates.

Corrigendum: Progress in thermomechanical control of steel plates and their commercialization.

[This corrects the article DOI: 10.1088/1468-6996/13/2/023001.].

English version of the interim report published in 1998 by the members of the Advisory Committee on Atopic Dermatitis Severity Classification Criteria of the Japanese Dermatological Association.

The Japanese Dermatological Association established an advisory committee in 1995 to set up severity scoring systems for atopic dermatitis (AD). Its interim report was published in Japanese in the Japanese Journal of Dermatology (108: 1491-1496, 1998) by Chairman Hikotaro Yoshida. Because of the strong demand for an English version, we have decided to publish the report in English. This prospective study was designed to evaluate the status of 259 AD patients using Method 1, which involves a simple global evaluation of disease severity; Method 2, which involves global evaluation by summing severity scores obtained from five body regions (i.e. the head and neck, anterior and posterior trunks, and upper and lower limbs); Method 3, which consists of both assessment of the extent of involved areas at each of the five body regions and that of the severity scores of each eruption component observed in the most severely affected body region; and Method 4, which consists of the evaluation of only subjective components (daytime pruritus and sleep disturbance). Employing the results obtained with Method 1 as a tentative benchmark, we analyzed its correlation with those of Methods 2, 3 and 4 to statistically assess the validity and reliability of these methods. Method 2, Method 3 and the portion of Method 4 involving evaluation of only the subjective symptom of daytime pruritus but not the sleep disturbance were considered useful in evaluating AD severity.

English version of the concluding report published in 2001 by the Advisory Committee on Atopic Dermatitis Severity Classification Criteria of the Japanese Dermatological Association.

The Japanese Dermatological Association established an advisory committee in 1995 to develop a severity scoring system for atopic dermatitis (AD). Its interim and concluding reports were published in Japanese in the Japanese Journal of Dermatology (108: 1491-1496, 1998 and 111: 2023-2033, 2001). Because of the strong demand for an English version, we have decided to publish the reports in English. This manuscript is the English version of the concluding report. The interim report suggested that eruption components such as erythema, papule, erosion, crust, excoriation and lichenification with extent of involved areas in five body regions, including the head and neck, anterior and posterior trunks, and upper and lower limbs, were important items for assessing AD severity. Additionally, it was recommended that streamlining of eruption components was mandatory for improving the statistical validity and reliability. The committee members subsequently concentrated their efforts on this task, and finally proposed an Atopic Dermatitis Severity Classification Criteria of the Japanese Dermatological Association.

[A case of anaphylaxis caused by abalone diagosed with prick by prick test].

A 30-year-old man exhibited systemic edema, dyspnea and wheal immediately after eating raw fish and cuttlefish served on an abalone shell. He had history of anaphylaxis after eating abalone and beef 4 years ago and had avoided shellfish including abalone since then. He also had past history of bronchial asthma and anaphylaxis due to shrimp. CAP-FEIA was performed to determine the allergen and was positive for scallop and oyster. Refined extracts made from abalone are not commercially available in Japan. Therefore, we purchased several kinds of shellfish, which are commonly consumed by Japanese, and used them, as is, for skin testing. Prick-by-prick tests were conduced using these shellfish, and yielded positive results for abalone and effluent from washing the abalone shell. Consequently, he was diagnosed with anaphylaxis caused by abalone extracts attached to the surface of raw fish. In our case, prick-by-prick test with shellfish was useful for the diagnosis of type I food allergy. If there are no commercial reagents of suspected food allergens for skin testing or challenge-test is not available, prick-by-prick tests might be performed for the diagnosis of food allergy.

Odontogenic focal infection could be partly involved in the pathogenesis of atopic dermatitis as exacerbating factor.

BACKGROUND: A focal infection has been reported to be associated with the pathogenesis of various skin diseases, but, to date, not atopic dermatitis (AD). The objective of the study was to clarify whether the odontogenic focal infection (OFI) could be recognized as one of the exacerbating factors in AD. METHODS: Forty-three patients with AD whose skin conditions were resistant to conventional therapy were examined. An OFI was evaluated by using radiographs. Serum IgE/sCD30 levels were also examined. Skin condition was evaluated by the eczema area and severity index (EASI). RESULTS: Odontogenic focal infection was detected in 13 patients (30%) and this incidence was higher than in the normal population. Moreover, a 3-month therapy including dental care improved the skin conditions of patients with OFI better than those without OFI. CONCLUSION: The study concluded that OFI could be involved in the pathogenesis of some types of AD as exacerbating factors.

Airborne contact dermatitis due to Japanese cedar pollen.

Contact dermatitis caused by airborne antigen is a well-recognized problem. Previously, airborne contact dermatitis after contact with Japanese cedar pollen [Japanese cedar pollen dermatitis (JCPD)] has been reported in Japan. However, there is still no diagnostic test to evaluate contact dermatitis due to Japanese cedar pollen. Skin tests with Japanese cedar pollen have been used to investigate these patients. A histological analysis was also conducted to clarify the mechanism of JCPD. We performed a scratch-patch test, scratch test and assays for total immunoglobulin E (IgE) and specific IgE in 13 patients suspected to have skin symptoms from Japanese cedar pollen, 5 patients with Japanese cedar pollinosis and 15 control normal subjects. All subjects were tested with Japanese cedar pollen allergen extract. A skin biopsy was performed from a Japanese cedar pollen-scratch-patch-test positive in patients with JCPD. The result after 48 hr of scratch-patch test was compared with the patient's history and the findings of corresponding scratch test and specific IgE. 100% of the 13 patients with JCPD showed a positive scratch-patch-test reaction to Japanese cedar pollen extract. However, 20% of the patients with the Japanese cedar pollinosis without any eruptions showed a positive scratch-patch-test reaction. The percentage of positive results for specific IgE and the scratch test did not differ substantially between Japanese cedar pollionosis patients with a history of chronic erythema after contact with Japanese cedar pollen and those without such a history. No side-effects were observed regarding the scratch-patch test. Control subjects showed 7% positive reaction. Histological examination showed that eczematous change (spongiosis, intracellular oedema and acanthosis), and infiltration of lymphocytes and eosinophils were all observed at the scratch-patch-test-positive sites. We therefore concluded that the use of the scratch-patch test with Japanese cedar pollen extract was useful for accurately diagnosing JCPD.

The SYT-SSX fusion protein down-regulates the cell proliferation regulator COM1 in t(x;18) synovial sarcoma.

Chromosomal translocations are frequently associated with soft-tissue sarcomas. Fusion proteins generated by such translocations often play critical roles in tumorigenesis. Therefore, it is important to understand the function of the fusion protein to develop therapeutic interventions. The t(X;18)(p11.2;q11.2) translocation found in synovial sarcomas results in a fusion between the SYT gene on chromosome 18 and an SSX gene on the X chromosome. Although SYT-SSX fusion proteins appear to trigger synovial sarcoma development, little is known about the downstream targets of SYT-SSX. We found that the SYT-SSX fusion protein produces a dominant-negative function for SYT, which is a transcriptional coactivator. We then analyzed the gene expression profiles of SYT-SSX1-expressing HeLa cells using oligonucleotide microarrays and found that the SYT-SSX1 fusion protein directly down-regulated the expression of COM1, a regulator of cell proliferation. COM1 was found to be expressed at relatively low levels in synovial sarcoma tissues and cell lines. We then investigated the impact of conditional COM1 expression in the synovial sarcoma cell line. Increased COM1 expression resulted in induced apoptosis and in reduced cell growth and colony formation activity. Our results suggested that restoration of COM1 expression may be of therapeutic benefit in synovial sarcoma.

Fas- and FasL-deficient mice are resistant to the induction of bleomycin-induced scleroderma.

We have recently shown that apoptosis is induced in the lesional skin in a murine scleroderma model by local bleomycin injections, and the apoptotic pathway was mainly mediated by Fas/Fas ligand (FasL) signaling. To further investigate the involvement of apoptosis in scleroderma, we examined whether the induction of dermal sclerosis is suppressed in Fas-deficient (lpr) and FasL-deficient (gld) mice. Results of histological examination showed that the induction of dermal sclerosis by bleomycin treatment was significantly suppressed in both lpr and gld mice, in comparison with wild-type mice. The ratio of collagen contents in the bleomycin-treated skin as compared with PBS-treated skin was significantly lower in both lpr and gld mice than that in wild-type mice. The number of TUNEL-positive infiltrating cells was markedly increased following bleomycin exposure (60 +/- 11.4/HPF) in comparison with PBS treatment (9.5 +/- 6.0/HPF) in wild-type mice, which was significantly decreased in both lpr (22 +/- 4.5/HPF, P < 0.05) and gld (26 +/- 6.1/HPF, P < 0.05) mice. Our findings that lpr and gld mice were resistant to the induction of dermal sclerosis by bleomycin further suggest that Fas/FasL pathway is an important contributor involved in the pathophysiology of bleomycin-induced dermal sclerosis.

[A case of "late-onset" anaphylaxis caused by fermented soybeans; Natto].

Natto is a Japanese traditional food made from fermented soybeans. We report a case of anaphylaxis caused by natto and review the literature. The patient was a 22-year-old man who showed systemic eruption with itching and pectoralgia about 10 hours after eating a meal containing natto. Results of skin tests for soybean allergen were negative, and the allergen remained unidentified. We then used a food elimination trial to confirm the allergy. However the patient did not refrain from eating natto, and he had three anaphylactic reactions might have been caused by natto. Each event occurred 10 to 14 hours after he ate a meal containing natto. We performed detailed examinations to determine the allergen. First, the prick-by-prick tests with natto and its characteristic viscous yarn-like surface were done and yielded positive results. Next, a provocation test with commercial natto (50 g) was performed and caused systemic eruption and pectoralgia about 9 hours after ingestion of the natto. The patients'plasma histamine level was elevated during the anaphylactic event. Anaphylaxis caused by natto was diagnosed. Recent studies have shown that the anaphylaxis caused by natto is of late-onset. Late-onset anaphylaxis can be considered one of IgE-mediated allergic reactions. The viscous surface of natto contains poly-gamma-glutamic acid (PGA). The hypothesized mechanism of late-onset anaphylaxis is delayed absorption or release of PGA into the bowel. In our case, the patient ate heated natto, we therefore speculate that suspect allergens were heat resistant. Patients with natto allergy must not eat natto, whether or not it is cooked or heated. Natto may induce allergic reactions up to a half-day after ingestion; thus, the clinical course and patient's diet must be considered during medical examination. Natto has recently gained popularity as a health food in foreign countries. The existence or natto allergy should be more widely recognized.

Prostaglandin D2 plays an essential role in chronic allergic inflammation of the skin via CRTH2 receptor.

PGD(2) plays roles in allergic inflammation via specific receptors, the PGD receptor designated DP and CRTH2 (chemoattractant receptor homologous molecule expressed on Th2 cells). We generated mutant mice carrying a targeted disruption of the CRTH2 gene to investigate the functional roles of CRTH2 in cutaneous inflammatory responses. CRTH2-deficent mice were fertile and grew normally. Ear-swelling responses induced by hapten-specific IgE were less pronounced in mutant mice, giving 35-55% of the responses of normal mice. Similar results were seen in mice treated with a hemopoietic PGD synthase inhibitor, HQL-79, or a CRTH2 antagonist, ramatroban. The reduction in cutaneous responses was associated with decreased infiltration of lymphocytes, eosinophils, and basophils and decreased production of macrophage-derived chemokine and RANTES at inflammatory sites. In models of chronic contact hypersensitivity induced by repeated hapten application, CRTH2 deficiency resulted in a reduction by approximately half of skin responses and low levels (63% of control) of serum IgE production, although in vivo migration of Langerhans cells and dendritic cells to regional lymph nodes was not impaired in CRTH2-deficient mice. In contrast, delayed-type hypersensitivity to SRBC and irritation dermatitis in mutant mice were the same as in wild-type mice. These findings indicate that the PGD(2)-CRTH2 system plays a significant role in chronic allergic skin inflammation. CRTH2 may represent a novel therapeutic target for treatment of human allergic disorders, including atopic dermatitis.

STAT-6-mediated control of P-selectin by substance P and interleukin-4 in human dermal endothelial cells.

P-Selectin expressed on endothelial cells contributes to acute and chronic inflammation by promoting leukocyte tethering/rolling. Despite increasing evidence of P-selectin expression on human umbilical vein endothelial cells in vitro, the regulatory mechanisms of P-selectin expression on dermal endothelial cells in skin diseases are not fully understood. Here, we demonstrate increased expression of P-selectin in dermal vessels of regional skin in urticaria and atopic dermatitis. The present in vitro analyses with human dermal microvascular endothelial cells (HDMECs) revealed that histamine rapidly induced P-selectin expression. Interleukin (IL)-4 and IL-13 induced prolonged expression of surface P-selectin by HDMECs. A combination of tumor necrosis factor-alpha and IL-4 inhibited P-selectin expression. Pretreatment of HDMECs with tumor necrosis factor-alpha followed by incubation with IL-4 markedly increased P-selectin expression. Notably, incubation with substance P alone induced prolonged P-selectin expression. Activation of STAT6 appears to be a key factor in P-selectin expression induced by substance P and IL-4 because treatment with STAT6 decoy oligodeoxynucleotides significantly inhibited P-selectin expression. The present results indicate that novel, complex mechanisms are involved in endothelial P-selectin expression in the skin. STAT6 in dermal endothelial cells appears to be a potent target for controlling cellular infiltrate in allergic and/or neuroinflammatory skin diseases.

Japanese cedar pollen as an exacerbation factor in atopic dermatitis: results of atopy patch testing and histological examination.

Atopy patch testing with Japanese cedar pollen extract has been used to investigate patients with atopic dermatitis whose condition is exacerbated by contact with Japanese cedar pollen. Comparative atopy patch testing, scratch tests, and assays for total IgE and specific IgE were performed in 74 patients with atopic dermatitis, 5 patients with Japanese cedar pollinosis and 15 control subjects. A skin biopsy was performed on any sites that were positive to Japanese cedar pollen patch test. The results after 48 h of atopy patch testing were compared with the patient's history, skin scratch test and specific IgE. Twenty-two of the 74 patients (30%) had a history of exacerbation every spring after contact with Japanese cedar. Of these patients 68% showed a positive reaction to Japanese cedar pollen extract, as did 21% of patients with atopic dermatitis without a history of exacerbation by Japanese cedar pollen, 20% of patients with Japanese cedar pollinosis without eruption and 7% of control subjects. A histological examination revealed eczematous changes and infiltration of lymphocytes and eosinophils in atopy patch testing positive sites. In conclusion, atopy patch testing with Japanese cedar pollen extract is a useful method for investigating trigger factors for eczematous skin lesions in a subgroup of patients with atopic dermatitis.

Multiple cutaneous fibrous histiocytomas in association with systemic lupus erythematosus.

Cutaneous fibrous histiocytomas are usually regarded as superficial lesions and commonly known as dermatofibromas; however, unusual cases histologically showing fibrohistiocytic proliferation extending into the deeper dermis or subcutaneous tissues are occasionally experienced. Some authors propose this type as benign fibrous histiocytoma of the skin, distinct from dermatofibroma. We describe herein a case of systemic lupus erythematosus (SLE) who developed multiple nodules on the face, trunk and extremities. The nodule on the forehead did not present a typical clinical appearance of dermatofibroma, and histopathological examination showed fibrohistiocytic proliferation with a storiform pattern extending into the deep dermis and subcutaneous tissues. By contrast, histology of the nodule on the abdomen showed fibrohistiocytic proliferation confined to the dermis and compatible with dermatofibroma. Although multiple dermatofibromas are occasionally seen in patients with SLE, benign fibrous histiocytoma of the skin showing deeper invasion than dermatofibroma is rarely associated with SLE.

Psoriasis arthropathy and HLA-B51: report of 5 cases.

Psoriasis arthropathy (PsA) is a chronic inflammatory arthropathy characterized by the association of arthritis with psoriasis. Although the precise mechanisms of PsA still remain obscure, several genetic and environmental factors have been suggested to play important roles. HLA-B51 has been strongly associated with Behçet's disease; however, its association with PsA has not been documented. We describe herein five Japanese patients (4 males and 1 female) with PsA and positive for HLA-B51. The clinical forms defined by Moll and Wright revealed that the polyarticular pattern was noted in two cases, and oligoarticular, distal, and spondyloarthropathy patterns were noted in one case each. Positive rheumatoid factor was detected in one patient, and antinuclear antibody in two patients. The other HLA subclasses were A2 and A31 in 3 cases, respectively. HLA-B51 was detected in 5 out of 17 patients with PsA examined in our department; in contrast, HLA-B51 was not detected in 17 patients with psoriasis vulgaris. Our observations suggest that HLA-B51 may play a role in the pathogenesis of PsA in the Japanese population.

Mycosis fungoides presenting as pigmented purpuric eruption.

A case of pigmented purpuric eruptions evolving to mycosis fungoides during the 4-year follow-up period is described. Clinical manifestation was characterized by petechial lesions with irregular shaped, diffusely pigmented plaques partly sharing morphological similarities with chronic pigmented purpura. Histologically, lymphocytes infiltrated around the capillaries of the superficial dermis with extravasated erythrocytes as well as into the epidermis to form Pautrier microabscesses. Whereas CD4+ cells were observed in the epidermis and upper dermis, CD8+ cells tended to be distributed around the capillaries. Notably, the Rumpel-Leede test revealed extensive punctuate purpura limited to the lesional skin. The aggregation response of platelets was not impaired. Either CD4+ tumor lymphocytes or CD8+ reactive lymphocytes appeared to induce capillary damage resulting in the formation of petechial lesions. Pigmented purpuric eruptions, such as atypical chronic pigmented purpura, is thus an important initial clinical manifestation of mycosis fungoides.