Association of polymorphisms of BTN2A1 and ILF3 with myocardial infarction in Japanese individuals with or without hypertension, diabetes mellitus or chronic kidney disease

Parkinson's disease (PD) is a common age-associated neurodegenerative disorder. To date, stem cell transplantation therapy has been developed to replace lost or damaged neural cells in PD patients, in whom dopaminergic neuron cells are lost. Here, we show that CD44+ human amniotic fluid cells (HuAFCs) can be induced to become functional dopaminergic neuronal-like cells in?vitro. Furthermore, when CD44+ or CD44- HuAFCs were transplanted into 6-hydroxydopamine (6-OHDA)-treated PD rats, the results indicated that CD44+ HuAFCs expressed multiple dopaminergic neuron cell markers and were ameliorative to behavioral recovery in PD rats after induction both in?vitro and in?vivo. CD44- HuAFCs did not fully differentiate into dopaminergic neuronal-like cells. When compared with CD44- HuAFCs, CD44+ HuAFCs showed increased activity in regeneration of dopaminergic neuron cell-like cells, increased migration distances, and improvement of animal behavior in the PD rat model. Therefore, CD44+ HuAFCs could be a source of dopaminergic neuronal-like cells with a potential use in cell-replacement therapy for PD.     

Pure red cell aplasia caused by parvovirus B19 in two patients without chronic hemolysis

Infection with human parvovirus B19 (PVB19) induces acquired pure red cell aplasia (PRCA). Chronic hemolytic anemia is well known as an underlying condition. However, additional factors have been recognized to accompany parvoviral PRCA; however, there are only limited reports on iron-deficiency anemia (IDA) and rituximab-induced B-cell dysfunction. We report two patients with PVB19-associated PRCA confirmed by positivity of viral DNA. Although they had no chronic hemolysis, patient 1 had IDA, and patient 2 had remitted small-lymphocytic lymphoma treated with rituximab-containing chemotherapy. Absence of reticulocytes in peripheral blood and marked depletion of erythroid precursors in bone marrow were observed both. Whereas patient 1 received only symptomatic therapy because anemia was not severe, patient 2 was treated with steroids, as PRCA etiology was at first uncertain, and immunological PRCA was not excluded. Both showed rapid increase of reticulocyte counts and recovery from anemia. Although immunoglobulin is considered effective for parvoviral PRCA, notable adverse reactions have been reported. When anemic symptom is not severe, reticulocyte observation only is recommended. The effects of steroids should also be re-evaluated. Optimal treatment according to disease severity remains to be established.     

Cloning and analysis of the ggpS gene from Cyanobacteria Arthrospira spp. involved in the synthesis of an osmolyte glucosylglycerol

The genus Arthrospira is a nonheterocystous filamentous cyanobacterium inhabiting diverse environments including those of high salinity. In the present study, Arthrospira strains were isolated from freshwater and brackish lakes in Myanmar, and their osmoprotective adaptation was investigated as it was for the genus Synechococcus strains. The Arthrospira strains showed satisfactory growth up to 1.0 M sodium chloride, suggesting their acclimation to high salinity stress. Cloning and phylogenetic analysis of ggpS, which encodes an osmolyte glucosylglycerol-phosphate synthase (GgpS), showed that the cyanobacterial strains possess a GgpS-based osmoprotective mechanism, except for Synechococcus strains of freshwater origin. The Arthrospira spp. strains fell into the same cluster in the GgpS phylogeny, suggesting their close taxonomic relationship. One exception was Arthrospira sp. TT-1 (II); the ggpS (II), possibly a paralogue of the ggpS (I), branched out from the cyanobacterial cluster. These findings suggest the wide distribution of the genus Arthrospira in freshwater to brackish environments is ascribed to its glucosylglycerol production as an osmoprotectant and resulting in salt acclimation.     

Application of tetramer technology in studies on autoimmune diseases

Autoreactive T cells are thought to play a role in the immunopathogenesis of autoimmune diseases. Analysis of such cells had long been hampered by lack of suitable assays. Recently developed tetramer technology is based on the recognition of specific peptide-MHC complex by T cell receptor and on the increased binding affinity of multimerized peptide-MHC complex. MHC class I and class II tetramers can be used to detect autoreactive CD4(+) and CD8(+) T cells, while nonclassical MHC (such as CD1d) tetramer can be used to detect other T cell groups, for example natural killer T cells. Tetramer technologies enable direct quantitation of autoreactive T cells in blood and affected tissues. It is also possible to carry out phenotypic and functional characterization of specific T cells on a single cell basis by using tetramers. Of special interest, in situ tetramer staining has the great potential of analyzing autoreactive T cells in their cellular environments. Utilization of tetramers in studies of autoreactive T cells is expected to generate important information regarding the role of such cells in the underlying mechanisms of autoimmune diseases.     

Efficacy of Enteral Supplementation Enriched with Glutamine,Fiber, and Oligosaccharide on Mucosal Injury following Hematopoietic Stem Cell Transplantation

The combination of glutamine, fiber and oligosaccharides (GFO) is thought to be beneficial for alleviating gastrointestinal mucosal damage caused by chemotherapy. A commercial enteral supplementation product (GFO) enriched with these 3 components is available in Japan. We performed a retrospective study to test whether oral GFO decreased the severity of mucosal injury following hematopoietic stem cell transplantation (HSCT). Of 44 HSCT patients, 22 received GFO and 22 did not. Severity of diarrhea/mucositis, overall survival, weight loss, febrile illness/documented infection, intravenous hyperalimentation days/hospital days, engraftment, acute and chronic GVHD, and cumulative incidence of relapse were studied. Sex, age, performance status, diagnosis, disease status, and treatment variables were similar in both groups. There were fewer days of diarrhea grade 3–4 in patients receiving GFO than in those who did not (0.86 vs. 3.27 days); the same was true for days of mucositis grade 3–4 (3.86 vs. 6.00 days). Survival at day 100 was 100% in the GFO group, but only 77.3% for the patients not receiving GFO (p = 0.0091, log-rank test). Weight loss and the number of days of intravenous hyperalimentation were better in the GFO group (p < 0.001 and p = 0.0014, respectively). Although not significant, less gut bacterial translocation with Enterococcus species developed in the GFO group (p = 0.0728) than in the non-GFO group. Other outcomes were not affected. To the best of our knowledge, this is the first comparative clinical study of GFO supplementation to alleviate mucosal injury after allo-HSCT. We conclude that glutamine, fiber and oligosaccharide supplementation is an effective supportive therapy to decrease the severity of mucosal damage in HSCT.Key words: Glutamine, Fiber, Oligosaccharide, GFO, Mucosal injury, Hematopoietic stem cell transplantation     

Y-box binding protein 1 enhances DNA topoisomerase 1 activity and sensitivity to camptothecin via direct interaction

Background

The Y-box binding protein 1 (YB-1) possesses pleiotropic functions through its interactions with various cellular proteins, and its high expression levels make it a potential useful prognostic biomarker for cancer cells. Eukaryotic DNA topoisomerases, such as DNA topoisomerase 1 (TOPO1) and DNA topoisomerase 2 (TOPO2), are the essential DNA metabolism regulators that usually overexpressed in cancer cells, and multiple proteins have been reported to regulate the enzyme activity and the clinical efficacy of their inhibitors. The present study unraveled the interaction of YB-1 with TOPO1, and further investigated the related function and potential mechanisms during the interaction.

Methods

The direct association of TOPO1 with specific domain of YB-1 was explored by co-immunoprecipitation and GST pull-down assays. The interaction function was further clarified by DNA relaxation assays, co-immunoprecipitation and WST-8 assays with in vitro gain- and loss- of function models.

Results

We found that YB-1 interacts directly with TOPO1 (but not with TOPO2) and promotes TOPO1 catalytic activity. Interactions between YB-1 and TOPO1 increased when cancer cells were treated with the TOPO1 inhibitor, camptothecin (CPT), but not with the TOPO2 inhibitor, adriamycin (ADM). Furthermore, we found that the interaction is prevented by pretreatment with the antioxidant agent, N-acetyl cysteine, and that YB-1 downregulation renders cells resistant to CPT.

Conclusions

Our findings suggest that nuclear YB-1 serves as an intracellular promoter of TOPO1 catalytic activity that enhances CPT sensitivity through its direct interaction with TOPO1.