Granulomatosis with polyangiitis (GPA), also known as Wegener's granulomatosis, is a systemic disease characterized by necrotizing granulomatous inflammation and vasculitis [1]. It commonly affects the upper and lower respiratory tract, kidneys and skin. The presence of serum anti-neutrophil cytoplasmic antibodies with antigen specificity for proteinase 3 (PR3-ANCA) is a highly sensitive marker for GPA. Skin lesions are observed in 35-50% of GPA patients [2]. We describe a GPA patient with a pyoderma [...]
Insulin resistance is one of the determinants of post-prandial hyperglycaemia. Recently, acarbose, an α-glucosidase inhibitor that delays the absorption of carbohydrates from the small intestine, has been found to reduce the incidence of cardiovascular disease in patients with impaired glucose tolerance or diabetes. However, the molecular mechanism by which acarbose inhibits cardiovascular events remains unknown. In this study, we examined whether oral administration of acarbose could suppress expression of monocyte chemoattractant protein-1 (MCP-1) in fructose-fed rats, a widely used animal model of insulin resistance. Serum MCP-1 levels were elevated in fructose-fed rats after 4 weeks. Acarbose treatment for 4 weeks reduced the fructose-induced elevation of serum MCP-1 levels. Acarbose treatment for 8 weeks decreased MCP-1 mRNA levels in the aortae of fructose-fed rats. These results suggest that the cardioprotective effects of acarbose could be due, at least in part, to the suppression of MCP-1 expression.
Extracellular toxin production in Clostridium perfringens is positively regulated by the two-component regulatory genes virR and virS. Northern (RNA) blots carried out with RNA preparations from the wild-type strain 13 and the isogenic virR and virS mutants TS133 and JIR4000 showed that the virR and virS genes composed an operon and were transcribed as a single 2.1-kb mRNA molecule. Primer extension analysis led to the identification of two promoters upstream of virR. Hybridization analysis of the mutants and their complemented derivatives showed that the virR/virS system positively regulated the production of alpha-toxin (or phospholipase C, theta-toxin (perfringolysin O), and kappa-toxin (collagenase) at the transcriptional level. However, the modes of regulation of these genes were shown to differ. The theta-toxin structural gene, pfoA, had both a major and a very minor promoter, with the major promoter being virR/virS dependent. The colA gene, which encodes the kappa-toxin, had two major promoters, only one of which was virR/virS-dependent. In contrast, the alpha-toxin structural gene, p1c, had only one promoter, which was shown to be partially regulated by the virR and virS genes. Comparative analysis of the virR/virS-dependent promoters did not reveal any common sequence motifs that could represent VirR-binding sites. It was concluded that either the virR/virS system modulates its effects via secondary regulatory genes that are specific for each toxin structural gene or the VirR protein does not have a single consensus binding sequence.
We herein report a typical case of alopecia neoplastica secondary to breast cancer. Alopecia neoplastica is a rare form of alopecia resulting from metastasis of a primary tumour to the scalp and is often misdiagnosed as alopecia areata.
Recent biochemical studies have shown that spectrin, protein 4.1, and actin form a skeletal protein network that underlines the inner surface of the erythrocyte membrane. The skeleton is a flexible structure that appears to be important in maintaining the shape and mechanical properties of the erythrocyte. Recent studies indicate that immunoanalogues of erythrocyte membrane skeletal proteins and ankyrin (protein 2.1) have been found in a wide variety of non-erythroid tissues. In the present study, in order to examine if human skin contains membrane skeletal proteins, immunochemical analysis was utilized using antibodies against anti-spectrin, anti-beta-fodrin (non-erythroid spectrin), anti-protein 4.1 and anti-ankyrin antibodies. Immunoblot analysis of human epidermis with anti-spectrin and anti-beta-fodrin antibodies revealed that human epidermis contains 240 kDa and 235 kDa spectrin-like proteins, which might be identical to brain fodrin. Human epidermis also contains 4.1-like proteins of 80 kDa and 78 kDa that cross react with anti-protein 4.1 antibodies, and contains ankyrin-like proteins of 210 kDa that cross react with anti-ankyrin antibodies. Analysis with immunofluorescence microscopy revealed that these antibodies reacted along the plasma membranes of human epidermal keratinocytes, eccrine sweat gland cells and sweat ductal cells. These results suggest that a membrane skeletal protein lattice might exist in these cells. Cultured human epidermal keratinocyte in the low Ca2+ medium (0.15 mM) showed that immunoreactive form of protein 4.1 and actin were present diffusely in the cytoplasm. When the cells were cultured with standardized Ca2+ medium (1.85 mM), protein 4.1 and actin were observed linearly along the cell margin and in the cytoplasm. Similar patterns of distribution were observed when anti-beta-fodrin antibody was used. Movement of membrane skeletal proteins from cytosol to the membrane suggest that these proteins or membrane skeletal lattice might play an important role in the formation of intercellular junctions.
