Enantioselective synthesis of stimulus-responsive amino acid via asymmetric α-amination of aldehyde

Development of a methodology to control the function of peptides and proteins is an indispensable task in the field of chemical biology and drug delivery. Recently, we reported synthesis of racemic stimulus-responsive amino acids and their application for controlling peptidyl function. In this study, we report enantioselective synthesis of a key intermediate of stimulus-responsive amino acids via asymmetric α-amination reaction of an aldehyde. The obtained chiral intermediate was converted to an Fmoc protected UV-responsive amino acid with (S)-configuration, and it was successfully incorporated into a model peptide by Fmoc solid phase peptide synthesis

Synthesis of a Stimulus-responsive Processing Device and Its Application to a Nucleocytoplasmic Shuttle Peptide

Stimulus-responsive processing (peptide bond cleavage) devices were developed. The processing reaction was triggered by stimulus-induced removal of a PG and the processing products were obtained in good purity. A photo-responsive processing device was successfully applied to develop a nucleocytoplasmic shuttle peptide. (F: fluorophore, NES: nuclear export signal. NLS: nuclear localization signal. PG: stimulusresponsive protective group

A novel atrial volume reduction technique to enhance the Cox maze procedure: Initial results

ObjectiveLarge left atrial diameter is reported to be a predictor for recurrent atrial fibrillation after the Cox maze procedure, and left atrial diameter by itself influences the chance of sinus rhythm recovery, as well as maintenance of sinus rhythm. However, additional cut-and-sew procedures to decrease left atrial diameter extend operative time and can cause bleeding. Thus we developed a no-bleeding, faster, and therefore less invasive left atrial volume reduction technique to enhance the Cox maze procedure.MethodsThe modified Cox maze III procedure with cryoablation or the left atrial maze procedure in association with mitral valve surgery was performed in 80 patients with atrial fibrillation and enlarged left atria (≥60 mm). Among them, 44 patients had the concomitant volume reduction technique (VR group); continuous horizontal mattress sutures for left atrial plication were placed on the left atrial wall along the pulmonary vein isolation line. Cryoablation was applied to the suture line so that the plicated left atrium is anatomically and electrically isolated. Another 36 patients did not have the volume reduction technique (control group).ResultsThe VR group had preoperative left atrial diameters similar to those of the control group (67.1 ± 7.8 vs 64.5 ± 6.7 mm) and a longer preoperative duration of atrial fibrillation (14.1 ± 5.4 vs 9.5 ± 5.1 years, P < .05) but had smaller postoperative left atrial diameters (47.6 ± 6.3 vs 62.1 ± 7.9 mm, P < .01). There were no differences in mean crossclamp/bypass time and chest tube drainage for 12 hours between the groups. Twelve months after surgical intervention, the sinus rhythm recovery rate of the VR group was better than that of the control group (90% vs 69%, P < .05).ConclusionsEven in patients with long-standing atrial fibrillation and an enlarged left atrium, maze procedures concomitant with the novel left atrial volume reduction technique improved the sinus rhythm recovery rate without increasing complications. Although further study with a larger number of patients and a longer follow-up period is needed, this safe and thus far potent technique that catheter-based ablation cannot copy might extend indication of the Cox maze procedure for patients with tough atrial fibrillation

Ornithine Decarboxylase Antizyme Induces Hypomethylation of Genome DNA and Histone H3 Lysine 9 Dimethylation (H3K9me2) in Human Oral Cancer Cell Line

Background: Methylation of CpG islands of genome DNA and lysine residues of histone H3 and H4 tails regulates gene transcription. Inhibition of polyamine synthesis by ornithine decarboxylase antizyme-1 (OAZ) in human oral cancer cell line resulted in accumulation of decarboxylated S-adenosylmethionine (dcSAM), which acts as a competitive inhibitor of methylation reactions. We anticipated that accumulation of dcSAM impaired methylation reactions and resulted in hypomethylation of genome DNA and histone tails. Methodology/Principal Findings: Global methylation state of genome DNA and lysine residues of histone H3 and H4 tails were assayed by Methylation by Isoschizomers (MIAMI) method and western blotting, respectively, in the presence or absence of OAZ expression. Ectopic expression of OAZ mediated hypomethylation of CpG islands of genome DNA and histone H3 lysine 9 dimethylation (H3K9me2). Protein level of DNA methyltransferase 3B (DNMT3B) and histone H3K9me specific methyltransferase G9a were down-regulated in OAZ transfectant. Conclusions/Significance: OAZ induced hypomethylation of CpG islands of global genome DNA and H3K9me2 by down-regulating DNMT3B and G9a protein level. Hypomethylation of CpG islands of genome DNA and histone H3K9me2 is a potent mechanism of induction of the genes related to tumor suppression and DNA double strand break repair

IgE, IgG, and IgG4 antibody titers to fractionated house dust mite antigens in nasal allergy patients.

Using 6 fractions differing in molecular weight of Dermatophagoides pteronyssinus (Dp)-antigen, we measured by enzyme-linked immunosorbent assay (ELISA) the titers of specific IgE, IgG and IgG4 antibodies against Dp antigen in sera of allergic subjects who were sensitive to house dust mite. We intended to evaluate which Dp fraction acts as the major antigenicity for allergic subjects. Results were as follows: 1) In comparison with normal controls, the titer of IgE antibody specific to crude Dp antigen was evaluated, but no significant difference was found among the titers of IgE antibody against each Dp fraction. 2) The titer of IgG antibody against the fraction with a high molecular weight (190 KD, 95 KD) was significantly higher than the titer of the 15 KD fraction in the nasal allergy patients. 3) The 15 KD fraction induced significant elevation of the titer of IgG4 antibody. It suggests that the low molecular weight fraction may act as the major allergenicity of Dp-antigen for inducing both IgE and competitive IgG4 antibodies, although other fractions induce significant IgE responses in patients with nasal allergy.</p

Usefulness of peripherally inserted central catheters

Introduction : Central venous catheter (CVC) use is essential for treating esophageal cancer. Peripherally inserted central catheters (PICC) are commonly used recently for improved patient comfort and safety. We compared centrally inserted central catheters (CICC) and PICC insertions and examined their safety. Methods : We retrospectively investigated complications at the catheter insertion and post-insertion for 199 patients’ esophageal cancer treatment (CICC : 45, PICC : 154) from 2013 to 2018. In addition, we summarized the results of catheter tip culture. Results : No serious complications occurred at the catheter insertion in either group. The rate of complications at catheter insertion was 5.8% for PICC and 6.7% for CICC patients. Post-insertion complications were observed in 6.5% and 11.1% of patients with PICC and CICC, respectively, and this difference was not significant. The incidence of catheter-related blood stream infection (CRBSI) was significantly lower in PICC than CICC patients (0.3 vs. 1.8 / 1,000 catheter-days ; p = 0.029). Catheter-related thrombosis was observed in PICC : 0.5 and CICC : 0.6, and occlusion due to blood flow reversal was observed in PICC : 0.5 and CICC : 0.6. Conclusion : PICCs are safer and more effective than CICCs for the treatment of esophageal cancer, and reduce the incidence of CRBSI. We hope to standardize the insertion procedures, conventionalize techniques, and establish training systems