ELAC2, a putative prostate cancer susceptibility gene product, potentiates TGF-beta/Smad-induced growth arrest of prostate cells.

Transforming growth factor-beta (TGF-beta) elicits a potent growth inhibitory effect on many normal cells by binding to specific serine/threonine kinase receptors and activating specific Smad proteins, which regulate the expression of cell cycle genes, including the p21 cyclin-dependent kinase (CDK) inhibitor gene. Interestingly, cancer cells are often insensitive to the anti-mitogenic effects of TGF-beta for which the molecular mechanisms are not well understood. In this study, we found that the candidate prostate cancer susceptibility gene ELAC2 potentiates TGF-beta/Smad-induced transcriptional responses. ELAC2 associates with activated Smad2; the C-terminal MH2 domain of Smad2 interacts with the N-terminal region of ELAC2. Small interfering siRNA-mediated knock-down of ELAC2 in prostate cells suppressed TGF-beta-induced growth arrest. Moreover, ELAC2 was shown to specifically associate with the nuclear Smad2 partner, FAST-1 and to potentiate the interaction of activated Smad2 with transcription factor Sp1. Furthermore, activation of the p21 CDK inhibitor promoter by TGF-beta is potentiated by ELAC2. Taken together our data indicate an important transcriptional scaffold function for ELAC2 in TGF-beta/Smad signaling mediated growth arrest.

[MRSA septicemia caused by an infected pacemaker lead: a case report with a review of Japanese literatures].

A 50-year-old woman was admitted to our hospital because of MRSA septicemia caused by a contaminated permanent pacemaker lead. A pacemaker system was successfully removed under cardiopulmonary bypass support. Postoperative antibiotics was administered for 7 weeks. Total removal of a pacemaker system under cardiopulmonary bypass support is the treatment of choice in a case with pacemaker infection associated with MRSA septicemia.

Relationship between the presence of periodontopathic bacteria and the expression of chemokine receptor mRNA in inflamed gingival tissues.

BACKGROUND AND OBJECTIVE: Periodontal disease is a chronic disease characterized by the interaction between periodontopathic bacteria and the host immune response. The aim of this study was to investigate the correlation between periodontopathic bacteria and host immune cell infiltrates. MATERIAL AND METHODS: Twenty-two patients with chronic periodontitis were included in this study. Gingival tissues were taken at the periodontal surgery after completion of initial therapy. Three types of periodontopathic bacteria were detected by polymerase chain reaction, and the prevalence of mRNA expression of chemokine receptors was examined by reverse-transcription-polymerase chain reaction in the gingival tissues. The infiltration of T and B cells was determined by an immunohistochemical method. RESULTS: In the patients, both Porphyromonas gingivalis and Tanerella forsythia were detected, and the mRNA expression of chemokine receptors CXCR1&2, CXCR4, CCR1, CCR2, CCR3 and CCR4 were more prevalent. The mean number of infiltrated B cells was significantly larger than that of T cells in the sites harboring both P. gingivalis and T. forsythia. Similarly, in the sites where P. gingivalis was detected but T. forsythia was not, the mean number of B cells was significantly larger than that of T cells. In the sites with mRNA expression of CCR2 and CCR3, the mean number of B cells was significantly larger. CONCLUSION: These results suggest that a high proportion of T helper 2-associated chemokine receptor-positive T cells may be associated with the predominance of B cells and may play an important role in the formation of chronic periodontitis in sites where both P. gingivalis and T. forsythia are detected.

Adipose cell size-function relationships: insulin binding and degradation.

125I-insulin binding and degradation have been studied in isolated rat adipose cells of increasing size. Binding at 24 degrees C reaches a steady state by 40-60 min in the absence of significant degradation. At 37 degrees C, binding reaches only a transient maximum by 10-15 min because insulin is rapidly degraded. Cellular enlargement is associated with increasing steady-state binding per cell at 24 degrees C, and increasing maximum binding and degradation per cell at 37 degrees C, in spite of increasing plasma insulin concentrations in the rats from which cells were prepared. Detailed steady-state studies at 24 degrees C, however, fail to delineate the mechanism of these alterations. Although dissociation experiments are consistent with the presence of a small degree of negatively cooperative binding site interaction, its magnitude is unchanged with increasing cell size. Furthermore, binding levels per unit cellular surface at 24 degrees C, at least at those insulin concentrations eliciting a biological response, remain relatively constant. None of the alterations in insulin binding observed here can explain the enlarged adipose cell's markedly decreased metabolic response to insulin.