Background: We evaluated the erythropoietic effects of canagliflozin, a sodium-glucose cotransporter 2 inhibitor, in type 2 diabetes patients with anemia of chronic kidney disease.Methods: Nine diabetes patients were enrolled and administered 100 mg canagliflozin once a day for 12 weeks. The patients received fixed doses of conventional antidiabetic drugs and renin-angiotensin system inhibitors for 8 weeks before enrollment; these drugs were continued during the study. Endpoints were changes in erythropoiesis parameters, including erythrocyte and reticulocyte count, hemoglobin, hematocrit, and serum erythropoietin (EPO) concentration from baseline to 12 weeks. All variables were measured every 2 weeks.Results: Serum EPO concentration increased by 38 [15–62]% (P = 0.043) between baseline and 2 and 4 weeks. Reticulocyte count transiently increased at 2 weeks. Erythropoiesis occurred after 2 weeks of canagliflozin treatment. Erythrocyte count (from 386 ± 36 × 104/μL to 421 ± 36 × 104/μL; P = 0.0009), hemoglobin (from 11.8 ± 0.6 g/dL to 12.9 ± 1.1 g/dL; P = 0.0049), and hematocrit (from 37.1 ± 2.3% to 40.4 ± 3.2%; P = 0.002) increased from baseline to study completion. Although there were no significant changes in transferrin saturation, serum ferritin levels were decreased (P = 0.003).Conclusions: Canagliflozin treatment led to an improvement in erythropoiesis in patients with impaired kidney function. The effect on erythropoiesis appeared to be due to an EPO production-mediated mechanism and might be independent of glycemic control; however, further studies are needed to clarify this since the present study had a small sample size and no comparator group.

Dendritic cells (DCs) are composed of multiple subsets that play a dual role in inducing immunity and tolerance. However, it is unclear how CD205+ conventional DCs (cDCs) control immune responses in vivo. Here we generated knock-in mice with the selective conditional ablation of CD205 + cDCs. CD205 + cDCs contributed to antigenspecific priming of CD4 + T cells under steady-state conditions, whereas they were dispensable for antigen-specific CD4 + T-cell responses under inflammatory conditions. In contrast, CD205 + T cells. Although most cells use MHC I molecules to present peptides derived from endogenously synthesized proteins, DCs have the capacity to deliver exogenous antigens to the MHC I pathway, a phenomenon known as cross-presentation, that underlies the generation of cytotoxic T lymphocyte (CTL) immunity (1-3). DCs thereby play a critical role in the link between innate and adaptive immunity. Conversely, DCs are also crucial for the induction of immunological tolerance under steady-state conditions, and the mechanisms involved include recessive tolerance mediated by deletion and anergy, and dominant tolerance by maintaining the homeostasis of self-reactive CD4 + Foxp3+ naturally occurring regulatory T cells (nTregs) and de novo generation of antigen-specific CD4 + Foxp3+ inducible Tregs (iTregs) (4-7). Mouse cDCs in lymphoid organs are comprised of two major subsets, classified as CD8α + cDCs and CD8α − cDCs. CD8α + cDCs mainly reside in the T-cell zone, and CD8α − cDCs reside in the red pulp and marginal zone (2, 8). Series of in vitro and ex vivo studies reported that CD8α+ cDCs compared with CD8α− cDCs strongly generate T-helper cell type 1 (Th1) cells because of the potential high-level production of IL-12 (9). In addition, CD8α + cDCs are more efficient in the phagocytic uptake of dead cells and in the cross-presentation of cell-bound or soluble antigens on MHC I to generate CTLs than other DC subsets (9).CD205, an endocytic type I C-type lectin-like molecule that belongs to the mannose receptor family, is mainly expressed on CD8α+ cDCs and cortical thymic epithelium, as well as interdigitating DCs in cutaneous lymph nodes (LNs) derived from dermal DCs and epidermal Langerhans cells (LCs), usually at a higher level than seen on macrophages and B cells (10-13). CD205 may function as an endocytic receptor involved in the uptake of extracellular antigens. Although an endogenous ligand for CD205 has not been identified, an antigen-conjugated mAb specific for CD205 was internalized, processed in the endosomal compartment, and presented to both MHC II and MHC I for cross-presentation with high efficiency (10). Although these observations based on analyses in vitro and ex vivo provide the functions of CD205 + cDCs, their role in the immune system under physiological conditions remains unclear because of the lack of a system that selectively eliminates this cell subset in vivo.To precisely evaluate the contribution of CD205 + cDCs to the immune system, we engineered knock-in mice that express the diphtheri...

SummaryThe results of chromosome studies on cultured umbilical cord blood lymphocytes from a consecutive series of 14,835 liveborn infants (7,608 males and 7,227 females) are described. Ninety-three infants (6.27 per 1,000) had a m~or chromosome abnormality. Of these, thirtyone infants (2.09 per 1,000) had sex chromosome abnormalities. Seven male infants had a 47,XXY karyotype, five had a 47,XYY karyotype, and three were mosaics. One male had a ring Y chromosome in all cells examined. A pericentric inversion of the Y chromosome was found in one case. Seven female infants had a 47,XXX karyotype, one had a 45,X karyotype and six were mosaics. Sixty-two infants (4.18 per 1,000) had autosomal abnormalities. There were twenty-one infants with trisomy 21 including one mosaic, six infants with trisomy 18, and two infants with trisomy 13 of a Robertsonian translocation type. Three infants had an unbalanced derivative chromosome resulting from a parental reciprocal translocation. Two infants with a partial monosomy of chromosome 13 were detected. There were four infants carrying an additional small marker chromosome. Twenty-four infants (1.62 per 1,000) had a balanced structural rearrangement of the autosomes; eleven with a Robertsonian translocation, eleven with a reciprocal translocation, and two with a pericentric inversion. The incidence of each type of major chromosome abnormality in this study was quite similar to that obtained from previous newborn surveys. Key Words chromosome abnormality, cytogenetic survey, newborn populationReceived December 21, 198921, ." revised version received February 7, 1991 Accepted February 8, 1991, 117 118 T. MAEDA et al.

In this study, we investigated the protective effect of glutamine on barrier dysfunction induced by ethanol, by using human epithelial colorectal adenocarcinoma cells (Caco-2). Our results show that addition of glutamine to culture medium significantly improved the disruption of integrity caused by ethanol, which was associated with increased expression of heat shock protein 70 (Hsp70). Ethanol exposure moderately activates heat shock factor 1 (HSF1), which was characterized by increased DNA-binding activity and phosphorylation status of HSF1. Remarkably, glutamine treatment enhanced ethanol-mediated expression of Hsp70 and activation of HSF1. Up-regulation of Hsp70 by pretreatment with heat stress also promoted recovery from the ethanol-induced barrier dysfunction. Taken together, these observations indicate that glutamine protects the intestinal barrier function in Caco-2 cells, in part by modulating HSF1-mediated Hsp70 expression.

We present a case of a 46,XY der(13;14) Robertsonian translocation carrier whose spermatozoa were karyotyped after injection into mouse oocytes. Fresh semen samples as well as recovered samples were used. There was no significant difference in the survival rate of mouse oocytes (fresh: 78.1% versus frozen: 81.7%), activation rate (fresh: 84.0% versus frozen: 90.6%), fertilization rate (fresh: 72.0% versus thawing of frozen: 76.5%) between fresh or frozen spermatozoa. Metaphase chromosome spreads from 45 spermatozoa were analysed. The frequency of spermatozoa that were chromosomally unbalanced with respect to the translocation was 8.9%, and the frequency of abnormalities unrelated to translocation was 4.4%. An excess of spermatozoa with balanced chromosomes was observed: compared with normal, 23 (51.1%) versus 16 (35.6%) respectively; but this segregation difference was not statistically significant (chi(2) = 0.9, P > 0.3). After genetic counselling with the carrier and his partner, intracytoplasmic sperm injection treatment was performed. Healthy female and male infants were delivered at 36 weeks gestation via a Caesarean section. Both babies were carriers for the balanced Robertsonian translocations detected for prenatal diagnosis at 16 weeks gestation. The present study demonstrates that patients can be given further information about the proportion of the spermatozoa which carry a chromosomal abnormality.