Generalized pustular psoriasis (GPP) is a rare disease characterized by recurrent fever and systemic flushing accompanied by extensive sterile pustules. The committee of the guidelines was founded as a collaborative project between the Japanese Dermatological Association and the Study Group for Rare Intractable Skin Diseases under the Ministry of Health, Labour, and Welfare Research Project on Overcoming Intractable Diseases. The aim of the guidelines was to provide current information to aid in the treatment of patients with GPP in Japan. Its contents include the diagnostic and severity classification criteria for GPP, its pathogenesis, and recommendations for the treatment of GPP. Since there are few clinical trial data with high levels of evidence for this rare disease, recommendations by the committee are described in the present guidelines.

Key words: basigin (CD147); malignant melanoma; invasion; metastasis; matrix metalloproteinaseBasigin (CD147), a transmembrane glycoprotein belonging to the Ig superfamily, was cloned from F9 embryonic carcinoma cells. 1 The Ig domain has strong homology with both the Ig variable domain and the major histocompatibility complex class II ␤ chain. It is expressed in various embryonic and adult tissues. 1,2 Because of its broad distribution, it was expected that basigin plays fundamental roles in various physiologic processes. Molecules identical to basigin were subsequently identified and given different names: M6 3 and EMMPRIN 4 in human; HT7, 5 neurothelin 6 and 5A11 7 in chicken; gp42 8 in mouse; and OX-47 9 and CE9 10 in rat. Of them, EMMPRIN, previously termed TCSF, has been implicated in the induction of MMPs. 4,11 Expression of EMMPRIN is enhanced in a variety of human carcinomas and correlates with tumor progression and invasion by inducing production of MMPs by stromal cells. 4,[11][12][13][14][15][16] It was also shown in vitro that recombinant EMMPRIN purified from Chinese hamster ovary cells transfected with cDNA for human EMMPRIN stimulates cultured human fibroblasts to produce MMP-1, MMP-2 and MMP-3. 17 EMMPRIN not only stimulates the production of interstitial collagenase (MMP-1) but also forms a complex with MMP-1 at the human lung carcinoma cell surface, which would facilitate invasive processes. 18 MMPs are a family of enzymes that degrade different components of the ECM, and a number of studies indicate that they play an important role in tissue remodeling, tumor invasion and metastasis. 19 -24 There are 2 distinct types of MMP, secreted and nonsecreted. Based on their substrate specificities, secreted MMPs are classified into collagenases (MMP-1, MMP-8 and MMP-13), gelatinases (MMP-2 and MMP-9) and stromelysins (MMP-3 and MMP-10). 20 Several nonsecreted MMPs are bound to membranes and designated MT-MMPs. 25 Tumor spread is a multistep process, which requires degradation or breakdown of the ECM and connective tissue and is caused by the concerted effects of these MMPs. 26 In the initial stage of tumor invasion, the gelatinases, particularly MMP-2, degrade components of the basement membrane, including type IV collagen. Although MMP-3, one of the stromelysins, also breaks down type IV collagen of the basement membrane, it degrades a variety of matrix components, including proteoglycans and noncollagenous glycoproteins such as laminin and fibronectin. Local tumor invasion is facilitated by collagenases, particularly MMP-1, which degrades the ECM. 20 MT1-MMP triggers tumor invasion by activating MMP-2. 25,27,28 Cutaneous MM is characterized by a high potential for invasion and metastasis. Previous studies reported the involvement of MMPs in migration, invasion, metastasis and progression of MM. Elevated expression of MMP-1, MMP-2 or MMP-9 was correlated with migration and invasion of cultured human melanoma cells. 21,22,29,30 In human melanoma lesions, positive correlations between tumor progressio...

Objectives. Myositis-specific autoantibodies (MSAs) are useful tools in identifying clinically homogenous subsets and predicting prognosis of patients with idiopathic inflammatory myopathies (IIM) including polymyositis (PM) and dermatomyositis (DM). Recent studies have revealed that anti-NXP2 antibody (Ab) is a major MSA in juvenile dermatomyositis (JDM). In this study, we evaluated the frequencies and clinical associations of anti-NXP2 Ab in adult IIM patients.Methods. Clinical data and sera were collected from 507 adult Japanese patients with IIM (445 adult DM, and 62 adult PM). As disease controls, 11 with JDM, 108 with systemic lupus erythematosus, 433 with systemic sclerosis, and 124 with idiopathic pulmonary fibrosis were assessed. Sera were examined for anti-NXP2 Ab by immunoprecipitation and Western blotting using polyclonal anti-NXP2 Ab.Results. Seven patients (1.6%) with adult DM and 1 (1.6%) with adult PM were positive for anti-NXP2 Ab. Except for 2 patients with JDM, no patients as disease controls were positive for this autoAb. Among 8 adult IIM patients, 3 had internal malignancies within 3 years of diagnosis of IIM. Another DM patient also had a metastatic cancer at the diagnosis. All of the carcinomas were advanced stage (stage IIIb-IV).Conclusions. While less common than in juvenile IIM, anti-NXP2 Ab was found in adult IIM. Anti-NXP2 Ab may be associated with adult IIM with malignancy.

CD147 plays a critical role in the invasive and metastatic activity of malignant melanoma cells by stimulating the surrounding fibroblasts to express matrix metalloproteinases and vascular endothelial growth factor. We developed a system that blocks CD147 in the human malignant melanoma cell line, A375, using RNA interference. By transfecting melanoma cells with the small interfering RNA (siRNA) that targets human CD147, we were able to establish two stable clones in which CD147 expression was significantly downregulated. This resulted in the decreased proliferation and invasion of A375 cells in vitro. CD147 siRNA also downregulated the expression of vascular endothelial growth factor in these cells and reduced the migration of vascular endothelial cells. The reduction in the CD147 level suppressed the size of s.c. tumors and the microvessel density in an A375 s.c. nude mouse xenograft model. In addition, the in vivo metastatic potential of A375 cells transfected with CD147 siRNA was suppressed in a nude mouse model of pulmonary metastasis. (Cancer Res 2006; 66(23): 11323-30)

Lotus tetragonolobus agglutinin (LTA) binds preferentially to early embryonic cells in the mouse. The affinity-purified antibody raised against LTA receptors from embryonal carcinoma cells were used to screen a lambda gt11 expression library of F9 embryonal carcinoma cells, resulting in detection of a cDNA clone specifying a new glycoprotein termed "basigin." The glycoprotein has been suggested to be a transmembrane one, and was found to be a new member of the immunoglobulin (Ig) superfamily. The molecular weight of basigin was largely in the range between 43,000 and 66,000, while that of the peptide portion with a putative signal sequence was inferred to be about 30,000. Significant levels of basigin mRNA were detected not only in embryonal carcinoma cells, but also in mouse embryos at 9-15 days of gestation and in various organs of the adult mouse. The Ig-like domain of basigin is unique, since it has strong homology to both the beta-chain of major histocompatibility class II antigen and the Ig V domain. The number of amino acids between the two conserved cysteine residues is intermediate between those of the Ig V and C domains. Therefore, basigin is an interesting protein in connection with the molecular evolution of the superfamily.

Prostaglandin E2 (PGE2) production in immortalized, nontransformed cells derived from wild-type, cyclooxygenase 1–deficient (COX-1−/−) or cyclooxygenase 2–deficient (COX-2−/−) mice was examined after treatment with interleukin (IL)-1β, tumor necrosis factor α, acidic fibroblast growth factor, and phorbol ester (phorbol myristate acetate). Compared with their wild-type counterparts, COX-1−/− or COX-2−/− cells exhibited substantially enhanced expression of the remaining functional COX gene. Furthermore, both basal and IL-1–induced expression of cytosolic phospholipase A2 (cPLA2), a key enzyme-regulating substrate mobilization for PGE2 biosynthesis, was also more pronounced in both COX-1−/− and COX-2−/− cells. Thus, COX-1−/− and COX-2−/− cells have the ability to coordinate the upregulation of the alternate COX isozyme as well as cPLA2 genes to overcome defects in prostaglandin biosynthetic machinery. The potential for cells to alter and thereby compensate for defects in the expression of specific genes such as COX has significant clinical implications given the central role of COX in a variety of disease processes and the widespread use of COX inhibitors as therapeutic agents.

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