Mutations in genes that encode polycystins 1 or 2 cause polycystic kidney disease (PKD). Here, we report the genomic organization and functional expression of murine orthologue of human polycystin-2L1 (PKD2L1). The murine PKD2L1 gene comprises 15 exons in chromosome 19C3. Coexpression of PKD2L1 together with polycystin-1 (PKD1) resulted in the expression of PKD2L1 channels on the cell surface, whereas PKD2L1 expressed alone was retained within the endoplasmic reticulum (ER). This suggested that interaction between PKD1 and PKD2L1 is essential for PKD2L1 trafficking and channel formation. Deletion analysis at the cytoplasmic tail of PKD2L1 revealed that the coiled-coil domain was important for trafficking by PKD1. Mutagenesis within two newly identified ER retention signal-like amino acid sequences caused PKD2L1 to be expressed at the cell surface. This indicated that the coiled-coil domain was responsible for retaining PKD2L1 within the ER. Functional analysis of murine PKD2L1 expressed in HEK 293 cells was undertaken using calcium imaging. Coexpression of PKD1 and PKD2L1 resulted in the formation of functional cation channels that were opened by hypo-osmotic stimulation, whereas neither molecule formed functional channels when expressed alone. We conclude that PKD2L1 forms functional cation channels on the plasma membrane by interacting with PKD1. These findings raise the possibility that PKD2L1 represents the third genetic locus that is responsible for PKD.
A 44-year-old woman was admitted with generalized lymphadenopathy, which was diagnosed as angioimmunoblastic T-cell lymphoma (AITL). The patient showed autoimmune hemolytic anemia (AIHA), polyclonal hypergammaglobulinemia and a high antinuclear antibody titer. Moreover, a human immunodeficiency virus (HIV)-1/2 screening test using the particle agglutination method was reactive. After chemotherapy for AITL, the AIHA was eliminated, and the false-positive HIV results were no longer detected. Autoimmunity associated with AITL is the likely cause of the cross-reaction with HIV and the AIHA. It is important to recognize that the cross-reaction with HIV can be a potential complication in AITL as well as AIHA.
We report a 47-year-old man with acute leukemia who survived a severe case of necrotizing fasciitis caused by Clostridium perfringens involving his right upper extremity. On day 5 after stem cell transplantation, progressive local tissue necrosis led to septicemia and disseminated intravascular coagulation. Early diagnosis and prompt initiation of appropriate therapy, including surgical debridement and broad-spectrum antibiotics, were crucial. A recombinant thrombomodulin might have not only resolved the coagulation problem but also prevented multiple organ failure associated with the systemic inflammatory response.
This study suggests that low-dose L-AmB may be an effective option as empirical antifungal therapy for high-risk patients with febrile neutropenia.
TO THE EDITORMultiple myeloma (MM) manifests as indolent neoplasms composed of plasma cells, but has a lethal clinical course and responds poorly to therapy. 1 In Japan, MM affects 2.4 men and 1.7 women per 100,000 individuals each year. The median age of onset is 66 years in Japan. 2 In recent years, MM treatments have changed dramatically, and new agents (such as proteasome inhibitors and immunomodulatory drugs) have been found to provide prolonged survival for patients with MM. 3,4 In a large retrospective study conducted at the Mayo Clinic, patients who were treated with the novel agents were observed to have longer survival following their initial diagnoses, as well as after relapse. 3 Several clinical trials have reported that the novel agents can achieve complete response, which is associated with improved progression-free and over-all survival. Bortezomib is superior to high-dose dexamethasone for the treatment of patients with MM who have experienced a relapse after 1 to 3 previous therapies. In comparison with high-dose dexamethasone, the hazard ratio (HR) for death with bortezomib was 0.57 (P = 0.001). 5 Two pivotal, phase III, randomized and placebo-controlled registration trials (MM-009 and MM-010) showed that lenalidomide plus dexamethasone was a more effective treatment regimen than placebo plus dexamethasone for patients with relapsed or refractory MM. 6,7 Overall survival was significantly improved in the lenalidomide group (HR for death, 0.66; P = 0.03). 6 The phase III VISTA (Velcade ® as Initial Standard Therapy in Multiple Myeloma) randomized clinical trial indicated that bortezomib plus melphalan and prednisone significantly prolongs overall survival in comparison with melphalan plus prednisone (HR, 0.653; P < 0.001). 8,9 This trial included a median follow-up of 36.7 months. Moreover, in the Front-Line Investigation of Revlimid ® /Dexamethasone vs. Standard Thalidomide (FIRST) randomized clinical trial, a doublet regimen of continuous oral lenalidomide in combination with low-dose dexamethasone was demonstrated to confer a statistically significant improvement in progression-free survival as a primary endpoint, in comparison with a comparator triplet regimen of melphalan, prednisone, and thalidomide. 10 The novel agents bortezomib and lenalidomide have been approved for MM treatment in Japan; however, limited data are available on the outcomes of treatment with these novel agents in clinical practice. Such data are important because treatment outcomes may differ substantially outside the highly regulated settings of randomized controlled trials. Shimizu et al. 11 investigated the survival of 1,383 Japanese patients with MM who were treated before the 89
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.