Our previous work established a role for actin associated myosin motor proteins MYH9 and MYH10 in the trafficking of thick ascending limb (TAL) specific cargoes, uromodulin (UMOD) and Na + K + 2Cl- cotransporter (NKCC2). Here, we have generated a TAL-specific Myh9&10 conditional knockout (Myh9&10 TAL-cKO) mouse model to determine the cell autonomous roles for MYH9&10 proteins in TAL cargo transport and to understand the consequence of TAL dysfunction in the adult kidney. Myh9&10 TAL-cKO mice develop progressive kidney disease with pathological tubular injury confirmed by histological changes, tubular injury markers, upregulation of ER stress/unfolded protein response pathway, and higher blood urea nitrogen and serum creatinine.
View Article and Find Full Text PDFAm J Physiol Renal Physiol
October 2024
This review highlights the complexity of renal epithelial cell membrane architectures and organelles through careful review of ultrastructural and physiological studies published over the past several decades. We also showcase the vital roles played by the actin cytoskeleton and actin-associated myosin motor proteins in regulating cell type-specific physiological functions within the cells of the renal epithelium. The purpose of this review is to provide a fresh conceptual framework to explain the structure-function relationships that exist between the actin cytoskeleton, organelle structure, and cargo transport within the mammalian kidney.
View Article and Find Full Text PDFWell-differentiated papillary mesothelioma (WDPM) is a rare mesothelial tumor of uncertain malignant potential. We present a unique case of a woman with synchronous WDPM and well-differentiated endometrioid adenocarcinoma (EA) arising from extraovarian endometriosis. A 56-year-old postmenopausal woman presented with a several-month history of right lower quadrant abdominal pain.
View Article and Find Full Text PDFPeritoneal carcinomatosis (PC) is a complex manifestation of abdominal cancers, with a poor prognosis and limited treatment options. Recent work identifying high concentrations of the cytokine interleukin-6 (IL-6) and its soluble receptor (sIL-6-Rα) in the peritoneal cavity of patients with PC has highlighted this pathway as an emerging potential therapeutic target. This review article provides a comprehensive overview of the current understanding of the potential role of IL-6 in the development and progression of PC.
View Article and Find Full Text PDFPurpose: To determine the feasibility of the surgical procedure and to collect some safety data regarding the bioelectronics of a novel micro drug pump for intravitreal drug delivery in a Beagle dog model for up to 1 year.
Methods: Thirteen Beagle dogs were assigned to two groups. The experimental group ( = 11) underwent pars plana implantation of MicroPump; the body of which was sutured episclerally, while its catheter was secured at a pars plana sclerotomy.
Purpose: To demonstrate the safety and surgical feasibility of the first-in-man ocular implant of a novel Posterior MicroPump Drug Delivery System (PMP) in patients with diabetic macular edema (DME) and to report on the device capabilities for delivering a programmable microdose.
Methods: This was a single center, single arm, open-label, prospective study. Eleven patients with DME and visual acuity equal to or worse than 20/40 were included.