Search

Background: Although cancer management in dialysis patients has become a commonly encountered issue, known as “onco-nephrology”, few evidence-based clinical recommendations have been proposed. Here, we examined the variation in referral behaviors adopted by dialysis physicians on encountering dialysis patients with signs/symptoms suggestive of cancer. Methods: We conducted a vignette-based study in August 2015. We sent a 14-page questionnaire to 191 dialysis physicians, including the representative dialysis facilities participating in a Japanese dialysis cohort (the Japan Dialysis Outcomes and Practice Patterns Study). Using vignette scenarios for respiratory, digestive, and urological areas, we assessed the referral behaviors (expert referral or not) adopted by dialysis physicians on encountering dialysis patients with symptoms suggestive of cancer. Each scenario contained three patient functional factors: age (60 or 75 years), performance status (PS 0 or 1), and cognitive dysfunction (absence or presence). We examined the association between physician factors, patient factors, and referral behaviors. Results: We obtained 94 replies (response rate: 49.2%). For the respiratory scenarios, 38.3% and 51.9% of physicians reported watchful waiting when encountering bilateral and unilateral pleural effusion, respectively. In digestive and urologic scenarios, most physicians (>85%) selected expert referral. We detected differences in referral behaviors between scenarios with different cancer biological factors. However, we found consistency in referral behaviors within the same scenario, even with different patient functional factors (intra-class correlation coefficients within each scenario all >0.7). Conclusions: Physicians’ referral behaviors for dialysis patients suspected of having cancer vary for different cancer biological factors (probability of having cancer). However, the referral behaviors are similar for different patient functional factors (age, PS, and cognitive dysfunction). [ABSTRACT FROM AUTHOR]

Supernumerary teeth and tooth agenesis are common morphological anomalies in humans. We previously obtained evidence that supernumerary maxillary incisors form as a result of the successive development of the rudimentary maxillary incisor tooth germ in Usag-1 null mice. The development of tooth germs is arrested in Runx2 null mice, and such mice also exhibit lingual epithelial buds associated with the upper molars and incisors. The aim of this study is to investigate the potential crosstalk between Usag-1 and Runx2 during tooth development. In the present study, three interesting phenomena were observed in double null Usag-1-/-/Runx2-/- mice: the prevalence of supernumerary teeth was lower than in Usag-1 null mice; tooth development progressed further compared than in Runx2 null mice; and the frequency of molar lingual buds was lower than in Runx2 null mice. Therefore, we suggest that RUNX2 and USAG-1 act in an antagonistic manner. The lingual bud was completely filled with odontogenic epithelial Sox2-positive cells in the Usag-1+/+/Runx2-/- mice, whereas almost no odontogenic epithelial Sox2-positive cells contributed to supernumerary tooth formation in the rudimentary maxillary incisors of the Usag-1-/-/Runx2+/+ mice. Our findings suggest that RUNX2 directly or indirectly prevents the differentiation and/or proliferation of odontogenic epithelial Sox2-positive cells. We hypothesize that RUNX2 inhibits the bone morphogenetic protein (BMP) and/or Wnt signaling pathways regulated by USAG-1, whereas RUNX2 expression is induced by BMP signaling independently of USAG-1. [ABSTRACT FROM AUTHOR]

Nephrin is a critical component of glomerular filtration barrier, which is important to maintain glomerular structure and avoid proteinuria. Downregulation of nephrin expression is commonly observed at early stage of glomerular disorders, suggesting that methods to increase nephrin expression in podocytes may have therapeutic utility. Here, we generated a knockin mouse line carrying single copy of 5.5 kb nephrin promoter controlling expression of enhanced green fluorescent protein (EGFP) at Rosa26 genomic locus (Nephrin-EGFP mouse). In these mice, EGFP was specifically expressed in podocytes. Next, we isolated and cultivated glomeruli from these mice, and developed a protocol to automatically quantitate EGFP expression in cultured glomeruli. EGFP signal was markedly reduced after 5 days of culture but reduction was inhibited by vitamin D treatment. We confirmed that vitamin D increased mRNA and protein expression of endogenous nephrin in cultivated glomeruli. Thus, we generated a mouse line converting nephrin promoter activity into fluorescence, which can be used to screen compounds having activity to enhance nephrin gene expression. [ABSTRACT FROM AUTHOR]