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Abstract Background Abnormal NF-κB2 activation has been implicated in the pathogenesis of multiple myeloma, a cancer of plasma cells. However, a causal role for aberrant NF-κB2 signaling in the development of plasma cell tumors has not been established. Also unclear is the molecular mechanism that drives the tumorigenic process. We investigated these questions by using a transgenic mouse model with lymphocyte-targeted expression of p80HT, a lymphoma-associated NF-κB2 mutant, and human multiple myeloma cell lines. Methods We conducted a detailed histopathological characterization of lymphomas developed in p80HT transgenic mice and microarray gene expression profiling of p80HT B cells with the goal of identifying genes that drive plasma cell tumor development. We further verified the significance of our findings in human multiple myeloma cell lines. Results Approximately 40% of p80HT mice showed elevated levels of monoclonal immunoglobulin (M-protein) in the serum and developed plasma cell tumors. Some of these mice displayed key features of human multiple myeloma with accumulation of plasma cells in the bone marrow, osteolytic bone lesions and/or diffuse osteoporosis. Gene expression profiling of B cells from M-protein-positive p80HT mice revealed aberrant expression of genes known to be important in the pathogenesis of multiple myeloma, including cyclin D1, cyclin D2, Blimp1, survivin, IL-10 and IL-15. In vitro assays demonstrated a critical role of Stat3, a key downstream component of IL-10 signaling, in the survival of human multiple myeloma cells. Conclusions These findings provide a mouse model for human multiple myeloma with aberrant NF-κB2 activation and suggest a molecular mechanism for NF-κB2 signaling in the pathogenesis of plasma cell tumors by coordinated regulation of plasma cell generation, proliferation and survival.

Background: Diabetic kidney disease is the most common cause of ESRD. There is poor correlation between the degree of renal fibrosis and current screening markers. A noninvasive imaging technique is needed to assess the degree of structural changes in the kidney. The aim of this study was to assess the role of apparent diffusion coefficient (ADC) in the diagnosis of diabetic kidney disease. Forty adult diabetic patients with chronic kidney disease as well as 20 age- and sex-matched adult healthy controls were recruited from Nephrology Department of our University Hospital. All patients underwent renal MR-DWI and ADC mapping on a 1.5-T scanner (Philips Achieva) using phased array body coil. Results: Among the studied 40 diabetic patients, five groups of patients were resulted 8 patients for each and the ADC values were inversely correlated with advancement in renal parenchymal affection, ie, in late stages of the disease the ADC values were lower than in early stages. The mean ADC values of renal parenchyma in patients with diabetic kidney disease were considerably lower than that of healthy controls with normal renal function (2.1± 0.3x10− 3 mm2/s vs 2.4± 0.1x10− 3 mm2/s with p< 0.001). Conclusion: ADC value is a possible noninvasive technique in evaluating the stage of renal dysfunction with assessment of disease progression. [ABSTRACT FROM AUTHOR]

Purpose: Anorganic bovine hydroxyapatite matrix (ABM), when coupled with synthetic cell-binding peptide (P15), mimics the cell-binding region of type 1 collagen and is commercially available suspended in a sodium hyaluronate carrier. The aim of the present study, therefore, was to test the efficacy of ABM/P-15 Putty (DENTSPLY Friadent CeraMed) as a sole graft material for sinus augmentation in patients with severely resorbed posterior maxillae. Materials and Methods: Sinus augmentation was performed in 10 patients using ABM/P-15 Putty and two provisional dental implants (3.0 mm in diameter). The graft and implants were placed simultaneously with the aid of a surgical stent. After 8 or 16 weeks, the implants were removed using a 4.25-mm trephine bur; this was followed by immediate placement of wider-diameter (5.5-mm) implants. All 20 implants were scanned by microcomputed tomography to determine bone mineral density (BMD), percent bone volume (PBV), and percent bone contact (PBC). Results: There was a significant increase in the BMD of bone around the implants at 8 weeks and 16 weeks compared to native residual (control) bone. There was no significant difference in PBV or PBC between 8 weeks and 16 weeks. The average increase in bone height at 16 weeks was 9.63 ± 1 mm. Microcomputed tomographic images and histologic sections showed dense graft particles surrounded by vital trabecular bone. Conclusion: BMD increases as early as 8 weeks and does not show an additional increase after 16 weeks. PepGen P-15 Putty was found to be a promising osteoconductive graft for sinus augmentation, supporting immediate placement of implants. [ABSTRACT FROM AUTHOR]