Early upsurge in anti-HBs titer possibly caused by the immunomodulative, not by the mutagenetic effect of interferon and ribavirin

A patient with chronic hepatitis B and C undergoing treatment with interferon and ribavirin showed an upsurge in hepatitis B virus surface antibody (anti-HBs) titer, accompanied by a decrease in hepatitis B virus surface antigen (HBsAg) during the early treatment phase. Simultaneously, elevation of alanine aminotransferase (ALT) was observed. Subsequently, the hepatitis B virus (HBV) DNA titer decreased and HBV e antigen (HBeAg) to anti-HBe seroconversion occurred. The anti-HBs titer gradually returned to the pretreatment level after cessation of ribavirin treatment and HBV-DNA became undetectable. We found no nucleotide mutations in HBV-DNA that could explain the sudden elevation in anti-HBs titer. The appearance of anti-HBs was considered to be a break in immune tolerance against some epitopes in HBsAg, possibly the r epitope, stimulated by interferon/ribavirin treatment. The immunomodulatory effect of ribavirin might have caused this unexpected early immune response to HBsAg that preceded seroconversion to anti-HBe.     

ONO-5334, a cathepsin K inhibitor,improves bone strength by preferentially increasing cortical bone mass in ovariectomized rats

This study compared the effects of ONO-5334, a cathepsin K inhibitor, with those of alendronate on bone mass and strength in ovariectomized rats. Ovariectomy resulted in significant elevation in urinary deoxypyridinoline and plasma C-terminal cross-linking telopeptide of type I collagen (CTX) 8 weeks after surgery. Peripheral quantitative computed tomography analysis showed that total, trabecular, and cortical bone mineral content (BMC) decreased in the proximal tibia, which was paralleled with a significant decline in bone strength. Treatment with ONO-5334 (0.12, 0.6, 3 or 15 mg/kg) once daily for 8 weeks dose-dependently restored the decrease in total BMC and bone mineral density (BMD) in the proximal tibia and suppressed urinary deoxypyridinoline and plasma CTX levels. Alendronate (1 mg/kg, once daily) also fully restored these bone mass parameters. Separate analysis of trabecular and cortical bones, however, showed that ONO-5334 only partially restored trabecular BMD and BMC at 15 mg/kg, whereas alendronate fully restored these parameters. On the other hand, ONO-5334 increased both cortical BMD and BMC with an effect more potent than that of alendronate. Bone geometric analysis indicated that ONO-5334 at 15 mg/kg decreased endosteal circumference without affecting periosteal circumference, resulting in marked increase in cortical thickness. Interestingly, the effects of ONO-5334 on bone strength parameters were more prominent than those of alendronate, although the two test compounds had a similar effect on total BMC. Taken together, our results indicate that ONO-5334 has pharmacological characteristics different from those of alendronate and may offer a unique therapy for patients with osteoporosis.     

Laparoscopic antireflux surgery improves esophageal body motility in patients with severe reflux esophagitis

Purpose

This study was designed to clarify whether laparoscopic antireflux surgery (LARS) improves the esophageal body motility (EBM) in patients with reflux esophagitis.

Methods

Thirty-five patients with gastroesophageal reflux disease (GERD) scheduled to undergo LARS were divided into a mild esophagitis group (ME; n = 18, Grade O:A:B = 7:10:1) and a severe esophagitis group (SE; n = 17, Grade C:D = 13:4), according to the Los Angeles classification of reflux esophagitis. The types of fundoplication (Nissen/Toupet) were 6/12 in the ME group and 4/13 in the SE group. Esophageal pH monitoring and manometry were performed before and 1 year after surgery.

Results

The fraction time of a pH below 4 significantly decreased after surgery in both groups. The LES pressures did not change significantly after surgery in the ME group, but significantly increased in the SE group. The peristaltic amplitudes 18 and 13 cm above the LES did not change significantly after surgery in either group. The peristaltic amplitudes 8 and 3 cm above the LES did not change significantly after surgery in the ME group, but significantly increased after surgery in the SE group.

Conclusions

The preoperative EBM was not improved by LARS in patients with GERD and mild mucosal breaks in the esophagus, but the preoperative middle to distal EBM was improved by LARS in patients with GERD and severe mucosal breaks.     

Synthesis and Characterization of End‐Functionalized Poly(3‐butylthiophene) with Semifluoroalkyl Chains

A new poly(3‐butylthiophene) derivative with one terminus functionalized with a 1H,1H,2H,2H,3H,3H‐perfluoroundecyl group (P3BT‐F₁₇) is synthesized by Ni‐catalyzed quasi‐living polymerization and the subsequent quenching of living ends by allyl‐Grignard reagent and the attachment of a fluoroalkyl chain. The quantitative introduction of fluoroalkyl chain ends is confirmed by matrix‐assisted laser desorption/ionization time‐of‐flight–mass spectrometry (MALDI‐TOF‐MS), gel‐permeation chromatography (GPC), ¹H NMR spectroscopy, and X‐ray photoelectron spectroscopy (XPS). The electronic properties of P3BT‐F₁₇ in solution and its crystalline structure in the solid state are investigated by UV–vis spectroscopy and cyclic voltammetry (CV), and by DSC and X‐ray diffraction (XRD) analyses.

     

An adequate perioperative management and strategy for gastric cancer after coronary artery bypass using the right gastroepiploic artery

Purpose

Interruption of the right gastroepiploic artery (RGEA) used for prior coronary artery bypass grafting (CABG) may cause life-threatening myocardial ischemia during gastrectomy. This study investigated the cases treated in this department and pooled data in the literature to identify an adequate perioperative RGEA management strategy.

Methods

Eight patients underwent gastrectomy after CABG with the RGEA. This study examined conditions, management of the RGEA, No. 6 lymph node metastasis, and complications of these cases and those in the pooled data.

Results

Percutaneous coronary intervention or a redo CABG was performed in advance in 7 and 1 patients, respectively. The RGEA was resected for dissection of No. 6 lymph nodes in 6 patients. Five patients had lymph node metastasis. Thirty-seven patients from 40 combined cases (92.5 %) underwent total or distal gastrectomy, but 17 patients (42.5 %) had RGEA resection. Resections of the RGEA and No. 6 lymph node metastasis were significantly higher in patients with perioperative coronary management than in those without such management.

Conclusion

Coronary and celiac angiography and coronary revascularization are prerequisites to prevent cardiac events during gastrectomy and dissection of No. 6 lymph nodes should be performed with resection of RGEA. Standard lymph node dissection should therefore be performed with a curative intent for all patients even those undergoing gastrectomy after CABG using RGEA.     

Evolutionarily conserved glycan signal to degrade aberrant brassinosteroid receptors in Arabidopsis

Asparagine-linked glycans (N-glycans) are crucial signals for protein folding, quality control, and endoplasmic reticulum (ER)-associated degradation (ERAD) in yeast and mammals. Although similar ERAD processes were reported in plants, little is known about their biochemical mechanisms, especially their relationships with N-glycans. Here, we show that a missense mutation in the Arabidopsis EMS-mutagenized bri1 suppressor 3 (EBS3) gene suppresses a dwarf mutant, bri1-9, the phenotypes of which are caused by ER retention and ERAD of a brassinosteroid receptor, BRASSINOSTEROID-INSENSITIVE 1 (BR1). EBS3 encodes the Arabidopsis ortholog of the yeast asparagine-linked glycosylation 9 (ALG9), which catalyzes the ER luminal addition of two terminal α1,2 mannose (Man) residues in assembling the three-branched N-glycan precursor [glucose(Glc)](3)(Man)(9)[N-acetylglucosamine(GlcNAc)](2). Consistent with recent discoveries revealing the importance of the Glc(3)Man(9)GlcNAc(2) C-branch in generating an ERAD signal, the ebs3-1 mutation prevents the Glc(3)Man(9)GlcNAc(2) assembly and inhibits the ERAD of bri1-9. By contrast, overexpression of EBS4 in ebs3-1 bri1-9, which encodes the Arabidopsis ortholog of the yeast ALG12 catalyzing the ER luminal α1,6 Man addition, adds an α1,6 Man to the truncated N-glycan precursor accumulated in ebs3-1 bri1-9, promotes the bri1-9 ERAD, and neutralizes the ebs3-1 suppressor phenotype. Furthermore, a transfer (T)-DNA insertional alg3-T2 mutation, which causes accumulation of an even smaller N-glycan precursor carrying a different exposed α1,6 Man, promotes the ERAD of bri1-9 and enhances its dwarfism. Taken together, our results strongly suggest that the glycan signal to mark an ERAD client in Arabidopsis is likely conserved to be an α1,6 Man-exposed N-glycan.