Novel dentin phosphoprotein frameshift mutations in dentinogenesis imperfecta type II

Lee K‐E, Kang H‐Y, Lee S‐K, Yoo S‐H, Lee J‐C, Hwang Y‐H, Nam KH, Kim J‐S, Park J‐C, Kim J‐W. Novel dentin phosphoprotein frameshift mutations in dentinogenesis imperfecta type II. The dentin sialophosphoprotein (DSPP) gene encodes the most abundant non‐collagenous protein in tooth dentin and DSPP protein is cleaved into several segments including the highly phosphorylated dentin phosphoprotein (DPP). Mutations in the DSPP gene have been solely related to non‐syndromic form of hereditary dentin defects. We recruited three Korean families with dentinogenesis imperfecta (DGI) type II and sequenced the exons and exon–intron boundaries of the DSPP gene based on the candidate gene approach. Direct sequencing of PCR products and allele‐specific cloning of the highly repetitive exon 5 revealed novel single base pair (bp) deletional mutations (c.2688delT and c.3560delG) introducing hydrophobic amino acids in the hydrophilic repeat domain of the DPP coding region. All affected members of the three families showed exceptionally rapid pulp chambers obliteration, even before tooth eruption. Individuals with the c.3560delG mutation showed only mild, yellowish tooth discoloration, in contrast to the affected individuals from two families with c.2688delT mutation. We believe that these results will help us to understand the molecular pathogenesis of DGI type II as well as the normal process of dentin biomineralization.     

Combinational Targeting Offsets Antigen Escape and Enhances Effector Functions of Adoptively Transferred T Cells in Glioblastoma

Preclinical and early clinical studies have demonstrated that chimeric antigen receptor (CAR)-redirected T cells are highly promising in cancer therapy. We observed that targeting HER2 in a glioblastoma (GBM) cell line results in the emergence of HER2-null tumor cells that maintain the expression of nontargeted tumor-associated antigens. Combinational targeting of these tumor-associated antigens could therefore offset this escape mechanism. We studied the single-cell coexpression patterns of HER2, IL-13Rα2, and EphA2 in primary GBM samples using multicolor flow cytometry and immunofluorescence, and applied a binomial routine to the permutations of antigen expression and the related odds of complete tumor elimination. This mathematical model demonstrated that cotargeting HER2 and IL-13Rα2 could maximally expand the therapeutic reach of the T cell product in all primary tumors studied. Targeting a third antigen did not predict an added advantage in the tumor cohort studied. We therefore generated bispecific T cell products from healthy donors and from GBM patients by pooling T cells individually expressing HER2 and IL-13Rα2-specific CARs and by making individual T cells to coexpress both molecules. Both HER2/IL-13Rα2-bispecific T cell products offset antigen escape, producing enhanced effector activity in vitro immunoassays (against autologous glioma cells in the case of GBM patient products) and in an orthotopic xenogeneic murine model. Further, T cells coexpressing HER2 and IL-13Rα2-CARs exhibited accentuated yet antigen-dependent downstream signaling and a particularly enhanced antitumor activity.     

海洋环肽噻唑氨基酸片断(D-Val)Thz的合成

近几年分离到的几个海洋环肽(ulicyclamide,ulithiacyclamide,patellamides,scidiacyclamide,dolastatin)的分子中都含有噻唑氨基酸结构。由于这些环肽有强烈的生理活性而引起人们广泛的研究。几个课题组都在从事其全合成及结构与生理活性关系的研究工作。而其中噻唑氨基酸是全合成中关键片断,对整个分子的生理活性也可能起着重要的作用。合成噻唑氨基酸有以下几种方法:     

Anatomic relationship between the common femoral artery and vein: CT evaluation and clinical significance

Knowledge of the anatomy of the common femoral artery (CFA) and common femoral vein (CFV) is important to minimize complications associated with transfemoral angiographic procedures. The authors assessed variations in the relationship between the CFA and the adjacent CFV by reviewing the inguinal region of 100 computed tomographic scans of the pelvis (200 vessel pairs). In 65% of the vessel pairs studied, a portion of the CFA overlapped the CFV in an anteroposterior plane. In addition, more than 25% of the artery overlapped the vein in 8% of the vessel pairs. This variation in anatomic relationship between the CFA and CFV is clinically significant, since a femoral vein puncture can be associated with simultaneous passage of the entry needle through the artery and thus formation of an arteriovenous fistula.