Association of the PTPN22 R620W polymorphism with increased risk for SLE in the genetically homogeneous population of Crete.

Autoimmune diseases affect approximately 5% of the population, but much work remains to define the genetic risk factors and pathogenic mechanisms underlying these conditions. There is accumulating evidence that common genetic factors might predispose to multiple autoimmune disorders. Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are complex autoimmune disorders with multiple susceptibility genes. The functional R620W (C1858T) polymorphism of the protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene, a member of the PTPs that negatively regulate T-cell activation, has been recently associated with susceptibility to various autoimmune diseases. The aim of this study was to assess whether the C1858T polymorphism of PTPN22 also confers increased risk for SLE and RA in the genetically homogeneous population of Crete. It was found that the minor T allele of the PTPN22 C1858T SNP was more common in SLE patients than in control individuals (odds ratio [OR] = 1.91, 95% confidence interval [CI] = 1.11 to 3.9, p = 0.017). No significant difference was observed in the frequency of this allele when RA patients were compared with controls (OR = 1.14, 95% CI = 0.65 to 1.9, p = 0.64). Although the PTPN22 1858 T allele is found at decreased frequency in Southern Europe, including Crete, an association was found between this allele and SLE in the population studied.

Extra-long projections of the cell surface in nonspecial-type ductal carcinoma with vascular invasion under the scanning electron microscope.

In this study, cell surface projections of primary culture cells from tissues of infiltrating ductal carcinoma Non Special Type with vascular invasion are examined by use of the Scanning Electron Microscopy method. In these cases the projections of cell membrane appeared extremely long and bridge-like covering very long distances between the breast cancer cells. Also, the long cell membrane projections, connect cells between them and form a complex. Sometimes, from one edge to another we observed a very long chain of cancer cells reaching sometimes a length of 3, 3 mm. On the other hand the absence of vascular invasion never shows such long projections of the cell membrane even if there are many metastatic nodes. The role of these extra long projections in communication between cancer cells is determinant. Through this communication, these long projections seemed to be responsible for the metastatic process in primary breast cancer with vascular invasion.

Inflammasomes and rheumatic diseases: evolving concepts.

The realisation that the production of inflammatory cytokines in inflammatory rheumatic diseases may be induced by non-infectious endogenous signals has encouraged researchers to explore mechanisms of innate immunity and their contribution to the pathogenesis of these diseases. The nucleotide-binding and oligomerisation domain (NOD)-like receptors (NLRs) sense pathogens, products of damaged cells or endogenous metabolites and could potentially be involved in the initiation, amplification and progression of the inflammatory response in rheumatic diseases. NLRs are involved in the regulation of innate immune responses with some of them promoting the activation of inflammatory caspases within multiprotein complexes, called inflammasomes. A typical inflammasome consists of a sensor, an NLR protein, an adaptor protein such as ASC (for apoptosis-associated speck-like protein containing a caspase recruitment domain (CARD)) and an effector protein that is a caspase that activates pro-inflammatory cytokines such as interleukin (IL)1beta and IL18. Recent data suggest a role of the inflammasome in the pathogenesis of autoinflammatory as well as inflammatory rheumatic diseases such as juvenile chronic arthritis, adult onset Still disease, rheumatoid arthritis and gout. Modulation of these pathways may be a potential therapeutic target for inflammatory rheumatic diseases.

Surface topography and ultrastructural changes of mucinous carcinoma breast cells.

Mucinous carcinoma of the breast (MCB) is histologically classified into 2 groups: (1) pure MCB and (2) mixed MCB. Pure MCB carries a better diagnosis than mixed MCB. This research relates to the cell surface topography and ultrastructure of the cells in the above cases and aims to find the differences between them, by means of two methods: scanning electron microscopy (SEM) and transmission electron microscopy (TEM). For the SEM examination, it was necessary to initially culture the MCB tissues and then proceed with the usual SEM method. In contrast, for the TEM technique, MCB tissues were initially fixed followed by the classic TEM method. The authors found the topography of pure MCB cases to be without nodes. The cell membrane was smooth, with numerous pores and small ruffles that covered the entire cell. The ultrastructural appearance of the same cases was with a normal cell membrane containing abundant collagen fibers. They also had many small vesicles containing mucin as well as secretory droplets. In contrast the mixed MCB had a number of lymph nodes and their cell surface topography showed stronger changes such as microvilli, numerous blebs, ruffles and many long projections. Their ultrastructure showed very long microvilli with large cytoplasmic inclusions and extracellular mucin collections, electron-dense material vacuoles, and many important cytoplasmic organelles. An important fact is that mixed MCB also contains areas of infiltrating ductal carcinoma. These cells of the cytoplasmic organelles are clearly responsible for the synthesis, storage, and secretion of the characteristic mucin of this tumor type. Evidently, this abnormal mucin production and the abundance of secretory granules along with the long projections observed in the topographical structure might be responsible for transferring tumor cells to neighboring organs, thus being responsible for metastatic disease.

Surface topography and ultrastructure correlation between human breast infiltrating ductal carcinoma of non special type and coexisting human breast infiltrating ductal carcinoma of non special type with in situ comedo carcinoma.

PURPOSE: To examine the topographical and ultrastructural correlations and differences between breast infiltrating ductal carcinoma (DC) non-special type (NST) and coexisting infiltrating DC NST with in situ comedo, in order to possibly detect differences in their metastatic potential. MATERIALS AND METHODS: The material examined derived from 22 women with breast cancer. Sixteen breast infiltrating DC NST tissue samples and 6 breast infiltrating DC NST with in situ comedo were studied with primary culture techniques, using transmission and scanning electron microscopy methods. RESULTS: The surface topography from infiltrating DC NST cells showed microvilli, blebs, ruffles, short and long projections. These features were absent in the normal breast cells. The intensity of these features was dependent on several histological characteristics. Also, the above features in coexisting DC NST with in situ comedo were related to more aggressive cases. The findings concerning the surface topography features have been also found in the ultrastructural level. A very interesting point was that these features consisted partly of cytoplasmic material. CONCLUSION: We believe that the presence of the features described above might be related to the metastatic potential of breast cancer and in particular to DC NST with in situ comedo.