The clinical spectrum of Fabry disease includes a "renal variant" phenotype in patients without classic symptoms who develop ESRD. Affected males undergoing hemodialysis or renal transplantation can be readily diagnosed by plasma alpha-Gal A assays. These patients and their family members may benefit from enzyme replacement therapy for the later, life-threatening cardiovascular and cerebrovascular complications of Fabry disease.

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...

Adult T-cell leukemia/lymphoma (ATLL) commonly involves the skin as well as peripheral blood and lymph nodes. During the last 15 years we have studied 124 cases of ATLL with specific skin manifestations. Twenty-one patients (16.9%) were classified as acute, 21 (16.9%) as chronic, 26 (21.0%) as lymphoma, and 56 (45.2%) as smouldering according to Shimoyama's classification. Many patients had nodules/tumors (34.7%), erythematous plaques (22.6%), and erythematous papules (19.4%) similar to those occurring with other cutaneous T-cell lymphomas. Some patients displayed characteristic skin manifestations resembling non-neoplastic cutaneous disorders. The median survival time (MST) of all patients was 12.0 months. The MSTs of individual clinical types were: acute type, 4 months; chronic type, 14 months; lymphoma type, 7 months; and smouldering type, 16 months. In the smouldering type, cases with a deeper infiltration pattern (MST, 14 months) had a more aggressive course than those with a superficial infiltration pattern (MST, 24 months) (p < 0.05). The results indicate that smouldering type ATLL with skin manifestations may have a worse prognosis than without skin manifestations. Moreover, some cases of the smouldering type with specific skin lesions should be classified into another group with a much poorer prognosis.

In the present study, we have shown that granulocyte and monocyte adsorption apheresis (GCAP), an extracorporeal apheresis instrument whose column contains cellulose acetate (CA) beads, is useful for skin diseases attributable to activated granulocytes and psoriatic arthritis (PsA). We assessed the clinical effectiveness of GCAP and investigated the mechanisms underlying the adsorption of pathogenic granulocytes. The effect of GCAP was assessed in 14 patients with neutrophilic dermatoses and 16 with PsA. The mechanisms by which the instrument adsorbs activated granulocytes were investigated using an in vitro mini-column system that mimics the GCAP. Skin lesions and arthropathy improved in 22 of 29 patients (75.9%) and 14 of 18 (77.8%), respectively. Mac-1 (CD11b/CD18) expression on the peripheral neutrophils, increased compared with normal subjects, was reduced by GCAP. In the mini-column system, CA beads adsorbed 50% neutrophils; and adsorption was inhibited significantly by treating plasma with EDTA and blood cells with antihuman CD11b monoclonal antibody. GCAP was useful for treating neutrophilic dermatoses and PsA. GCAP adsorbs Mac-1-expressing neutrophils to the CA beads by the binding of complement component (iC3b) on CA beads and CD11b expressed on activated neutrophils.

We compared two recombinant a-galactosidases developed for enzyme replacement therapy for Fabry disease, agalsidase alfa and agalsidase beta, as to specific a-galactosidase activity, stability in plasma, mannose 6-phosphate (M6P) residue content, and effects on cultured human Fabry fibroblasts and Fabry mice. The specific enzyme activities of agalsidase alfa and agalsidase beta were 1.70 and 3.24 mmol h À1 mg protein À1 , respectively, and there was no difference in stability in plasma between them. The M6P content of agalsidase beta (3.6 mol/mol protein) was higher than that of agalsidase alfa (1.3 mol/mol protein). The administration of both enzymes resulted in marked increases in a-galactosidase activity in cultured human Fabry fibroblasts, and Fabry mouse kidneys, heart, spleen and liver. However, the increase in enzyme activity in cultured fibroblasts, kidneys, heart and spleen was higher when agalsidase beta was used. An immunocytochemical analysis revealed that the incorporated recombinant enzyme degraded the globotriaosyl ceramide accumulated in cultured Fabry fibroblasts in a dose-dependent manner, with the effect being maintained for at least 7 days. Repeated administration of agalsidase beta apparently decreased the number of accumulated lamellar inclusion bodies in renal tubular cells of Fabry mice.