Calmodulin is essential for estrogen receptor interaction with its motif and activation of responsive promoter

Calmodulin (CaM) has been reported to have affinity for the estrogen receptor (ER). Observations reported here reveal a direct physical interaction between purified CaM and ER. This direct ER-CaM interaction may be an initial event preceding the assembly of ER plus auxiliary proteins into the active ER complex with its DNA motif, the estrogen response element. We demonstrate that CaM is an integral component of this complex by using a system reconstituted from purified ER and nuclear extract from ER-negative breast cancer cells and also with ER-depleted nuclear extract of an ER-positive breast cancer cell line. Although CaM is essential for formation of this complex, it is not sufficient, suggesting roles also of auxiliary proteins. CaM also is functionally required for activation of an ER-responsive promoter, in the 17beta-estradiol-ER pathway of hormone action and regulation of 17beta-estradiol-responsive gene expression that is associated with proliferation of mammary epithelial cells.     

Similarity and symmetry measures for convex shapes using Minkowskiaddition

This paper is devoted to similarity and symmetry measures for convex shapes whose definition is based on Minkowski addition and the Brunn-Minkowski inequality. This means, in particular, that these measures are region-based, in contrast to most of the literature, where one considers contour-based measures. All measures considered in this paper are invariant under translations; furthermore, they can be chosen to be invariant under rotations, multiplications, reflections, or the class of affine transformations. It is shown that the mixed volume of a convex polygon and a rotation of another convex polygon over an angle &thetas; is a piecewise concave function of &thetas;. This and other results of a similar nature form the basis for the development of efficient algorithms for the computation of the given measures. Various results obtained in this paper are illustrated by experimental data. Although the paper deals exclusively with the two-dimensional case, many of the theoretical results carry over almost directly to higher-dimensional spaces     

Efficacy of arthroscopic lysis and lavage in patients with temporomandibular joint symptoms associated with generalized osteoarthritis or rheumatoid arthritis

PURPOSE: This study evaluated the efficacy of arthroscopic lysis and lavage in patients with temporomandibular joint (TMJ) symptoms and generalized osteoarthritis (GOA) or rheumatoid arthritis (RA). PATIENTS AND METHODS: Twenty-three GOA patients and 23 RA patients were evaluated after 1 year. RESULTS: Seventeen of 23 patients (74%) in the RA group improved after arthroscopic lysis and lavages compared with 10 of 23 (43%) of the GOA patients. Lateral joint tenderness, crepitation, maximal opening, and maximal protrusion showed most improvement in the RA group. CONCLUSIONS: On the basis of this short-term follow-up study, arthroscopic lysis and lavage seem to provide an effective treatment for TMJ pain and dysfunction in RA patients but not in GOA patients.     

Early modifications of chemokine production and mRNA expression during rush venom immunotherapy

The mechanism by which specific immunotherapy exerts its beneficial effect remains unclear. Chemokines are implicated in inflammatory and allergic diseases, in particular via their ability to induce histamine release from basophils, a potential early target of rush venom immunotherapy (RVIT), In this study, the authors evaluated ex vivo regulated upon activation normal T-cell expressed and secreted (RANTES), interleukin 8 (IL-8) and monocyte chemoattractant protein 1 (MCP-1) production and mRNA expression by mononuclear cells (MNC) from nine patients undergoing a 3.5-h ultra rush treatment, before treatment at Day 0 (D0), at the end of the 3.5-h of the rush at Day 4h (D4h), at Day 15 (D15) and Day 45 (D45) after treatment. Increased RANTES release and mRNA expression were observed in 24-h culture of peripheral blood MNC collected at D4h. This was followed by a decrease in the production of RANTES, IL-8 and MCP-1, 45 days after initiation of RVIT. The same pattern was observed after in vitro venom stimulation of MNC. At the mRNA level, similar profiles were observed except for IL-8 mRNA which inversely increased during RVIT. These results suggest that RVIT is associated with a general decrease in chemokines which may explain, in part, the clinical efficacy of specific immunotherapy.     

Development of technologies aiding large-tissue engineering

Apoptosis associated oligonucleosomal fragmentation of DNA can result from the activation of endonucleases that exhibit different pH optima and are either sensitive or insensitive to divalent cations. DNA fragmentation due to activation of cation sensitive endonucleases occurs in the absence of a change in intracellular pH whereas intracellular acidification is a feature of apoptosis characterized by activation of cation insensitive acidic endonuclease. We have reported earlier that somatostatin (SST) induced DNA fragmentation and apoptosis is signaled in a receptor subtype selective manner uniquely via human somatostatin receptor subtype 3 (hSSTR3). In the present study we investigated the pH dependence and cation sensitivity of endonuclease induced in hSSTR3 expressing CHO-K1 cells by the SST agonist octreotide (OCT) and its effect on intracellular pH. We show that OCT induced apoptosis is associated with selective stimulation of a divalent cation insensitive acidic endonuclease. The intracellular pH of of cells undergoing OCT induced apoptosis was 0.9 pH units lower than that of control cells. The effect of OCT on endonuclease and pH was inhibited by orthovanadate as well as by pretreatment with pertussis toxin, suggesting that hSSTR3 initiated cytotoxic signaling is protein tyrosine phosphatase mediated and is G protein dependent. These findings suggest that intracellular acidification and activation of acidic endonuclease mediate wild type p53 associated apoptosis signaled by hormones acting via G protein coupled receptors.     

Reduced skin tumor development in cyclin D1-deficient mice highlights the oncogenic ras pathway in vivo

Cyclin D1 is part of a cell cycle control node consistently deregulated in most human cancers. However, studies with cyclin D1-null mice indicate that it is dispensable for normal mouse development as well as cell growth in culture. Here, we provide evidence that ras-mediated tumorigenesis depends on signaling pathways that act preferentially through cyclin D1. Cyclin D1 expression and the activity of its associated kinase are up-regulated in keratinocytes in response to oncogenic ras. Furthermore, cyclin D1 deficiency results in up to an 80% decrease in the development of squamous tumors generated through either grafting of retroviral ras-transduced keratinocytes, phorbol ester treatment of ras transgenic mice, or two-stage carcinogenesis.