The role of recombination signal sequences in the preferential joining by deletion in DH-JH recombination and in the ordered rearrangement of the IgH locus

The bias favoring deletion over inversion in DH-JH rearrangement has been known for years, but the underlying mechanism has yet to be fully defined. It has been suggested that the ratio of deletion/inversion is determined by the combined effect of two factors: (i) the relative strengths of 5' and 3' recombination signal sequences (RSS) of a DH segment, and (ii) the efficiency with which the deletional product (one joint) forms relative to the inversional product (two joints). In this study, we analyzed for the first time the effect of factor 1 alone on the biased 3' RSS utilization in DH-JH joining by using deletional plasmids in an extrachromosomal substrate V(D)J recombination assay. It was found that the 3' RSS and associated coding end (12 bp) mediate recombination more efficiently than the 5' RSS/coding end DH-JH plasmids. These results demonstrate that the effect of the RSS/coding end alone can account, at least partially, for the predominant deletion in DH-JH recombination. The potential effect of the relative strength of RSS and associated coding end on the ordered rearrangement of DH-JH followed by VH to DH-JH was also assessed. When recombination frequencies of D-->J (3' DH to J3) were compared with frequencies of V-- >D (VHPJ14 to 3' DH or VHOX2 to 3' DH), it was found that V-->D joining was, if anything, more efficient than D-->J joining. Therefore, if all three segments were accessible, RSS/coding end effects would not contribute to the ordered rearrangement of the IgH locus.      

Reduction of atherosclerosis in cholesterol-fed rabbits and decrease of expressions of intracellular adhesion molecule-1 and vascular endothelial growth factor in foam cells by a water-soluble fraction of Polygonum multiflorum

Polygonum multiflorum stilbeneglycoside （PMS） is a water-soluble fraction of Polygonum multiflorum Thunb. , one of the most famous tonic traditional Chinese medicines, that has protective effects on the cardiovascular system. The purpose of the present study is to elucidate the effects of PMS on macrophage-derived foam cell functions and the reduction of severity of atherosclerosis in hypercholesterolemic New Zealand White （NZW） rabbits. NZW rabbits were fed for 12 weeks with a normal diet, a high cholesterol diet, or a high cholesterol diet associated with irrigation with different doses of PMS （25, 50, or 100 mg/kg）. Treatment of NZW rabbits fed with high cholesterol diet with 100 mg/kg PMS attenuated the increase in plasma cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and plasma triglyceride. Treatment with 50 and 100 mg/kg PMS caused 43% and 60% decrease in atherosclerotic lesioned area ratio to total surface area, respectively. In U937 foam cells, PMS could decrease the high expression of intercellular adhesion molecule （ICAM）-1 protein and the vascular endothelial growth factor （VEGF） protein levels in the medium induced by oxidized lipoprotein when analyzed by flow cytometry. The results proved that PMS is a powerful agent against atherosclerosis and that PMS action could possibly be through the inhibition of the expression of ICAM-1 and VEGF in foam cells.     

单克隆抗体博来霉素A6偶联物对白血病细胞特异性结合与内化

抗CCT2单克隆抗体博来霉素A6偶联物可吸附胶体金颗粒(McAb-A6-Au)。电镜观察表明,在4℃,1h,表面有McAb-A6-Au颗粒的CEM细胞最高达78%;在37℃,4h,内化McAb-A6-Au颗粒的CEM细胞高达72%。而抗原性无关的U937细胞仅为14%。并且McAb-A6-Au颗粒能直接穿过细胞膜、核膜进入细胞浆和细胞核。37℃,1h已有10～18%的CEM细胞核内有McAb-A 6-Au颗粒。实验结果提示了单抗与博来霉素A6的偶联物与选择性地结合靶细胞,而且进入细胞速度快、穿透力强,有可能成为治疗白血病药物。     

Ischemic Gastric Conditioning by Preoperative Arterial Embolization Before Oncologic Esophagectomy: A Single-Center Experience

Purpose

Surgical esophagectomy is the gold standard treatment of early-stage esophageal cancer. The procedure is complicated with significant morbidity; the most severe complication being the anastomotic leakage. Anastomotic fistulas are reported in 5–25% of cases and are mainly due to gastric transplant ischemia. Here, we report our experience of ischemic pre-conditioning using preoperative arterial embolization (PreopAE) before esophagectomy.

Materials and Methods

The medical records of all patients who underwent oncologic esophagectomy from 2008 to 2015 were retrospectively reviewed. Patients were divided into two groups: patients who received PreopAE, and a control group of patients who did not benefit from ischemic pre-conditioning. The target arteries selected for PreopAE were the splenic artery, left gastric artery, and right gastric artery. Evaluation of the results was based on anastomotic leakage, postoperative mortality, technical success of PreopAE, and complications related to the embolization procedure.

Results

Forty-six patients underwent oncologic esophagectomy with PreopAE and 13 patients did not receive ischemic conditioning before surgery. Thirty-eight PreopAE were successfully performed (83%), but right gastric artery embolization failed for 8 patients. Anastomotic leakage occurred in 6 PreopAE patients (13%) and in 6 patients (46%) in the control group (p = 0.02). The mortality rate was 2% in the PreopAE group and 23% in the control group (p = 0.03). Eighteen patients suffered from partial splenic infarction after PreopAE, all treated conservatively.

Conclusion

Preoperative ischemic conditioning by arterial embolization before oncologic esophagectomy seems to be effective in preventing anastomotic leakage.

     

FISSURE SEALANT IN A NUTSHELL. EVIDENCE-BASED META-EVALUATION OF SEALANTS’ EFFECTIVENESS IN CARIES PREVENTION AND ARREST

ObjectiveThis meta-evaluation aimed to summarize all available evidence regarding different fissure sealants on occlusal caries prevention, arrest, retention rate, adverse effect, and cost-effectiveness; when compared with no intervention, other preventive or minimally-invasive procedures.Materials and MethodsThe systematic reviews and meta-analyses were identified via four electronic databases and manual searching. Two independent reviewers performed study selection, data extraction, quality assessment with AMSTAR-2.ResultsAmong the 366 records yielded, 38 systematic reviews were identified as eligible 24 of them included meta-analyses. Moderate evidence has supported the efficacies of resin-based sealants (RBS) in occlusal caries prevention, arrest and cost-effectiveness compared to no interventions. Low to very low certainty of evidence suggested similar effectiveness of glass-ionomer cements in caries prevention with RBS and more superior performance of resin infiltration in arresting non-cavitated occlusal lesions.ConclusionThis meta-evaluation supports the use of RBS on permanent molars to reduce occlusal caries occurrence, arrest lesion progression and alleviate oral health inequalities between individuals of different socioeconomic status. This meta-evaluation also advocates further research on glass-ionomer cements and resin infiltration with respect to their efficacies in caries prevention and arrest.     

Endobronchial closure of bronchopleural fistula with Amplatzer PFO device

Bronchopleural fistula (BPF) is a feared postoperative complication of pneumonectomy that carries significant morbidity and mortality. BPF can be treated by various surgical and medical techniques. Endobronchial techniques have been used for the delivery of biological glue, sealants, coils, and covered stents with variable degrees of success, depending on the size of the fistula. A recent case report described the endobronchial closure of a BPF through the implantation of an Amplatzer ASD device, commonly used for transcatheter closure of atrial septal defects. In this case report, we describe closure of a BFP using the Amplatzer PFO device.     

Superior vena cava graft infection in thoracic surgery: a retrospective study of the French EPITHOR database

 Open in a separate windowOBJECTIVESTo report our experience on the management of superior vena cava graft infection.METHODSBetween 2001 and 2018, patients with superior vena cava synthetic graft or patch reconstruction after resection of intrathoracic tumours or benign disease were selected retrospectively from the French EPITHOR database and participating thoracic centres. Our study population includes patients with superior vena cava graft infection, defined according to the MAGIC consensus. Superior vena cava synthetic grafts in an empyema or mediastinitis were considered as infected.RESULTSOf 111 eligible patients, superior vena cava graft infection occurred in 12 (11.9%) patients with a polytetrafluoroethylene graft secondary to contiguous contamination. Management consisted of either conservative treatment with chest tube drainage and antibiotics (n = 3) or a surgical graft-sparing strategy (n = 9). Recurrence of infection appears in 6 patients. Graft removal was performed in 2 patients among the 5 reoperated patients. The operative mortality rate was 25%.CONCLUSIONSSuperior vena cava graft infection may develop as a surgical site infection secondary to early mediastinitis or empyema. Graft removal is not always mandatory but should be considered in late or recurrent graft infection or in infections caused by aggressive microorganisms (virulent or multidrug resistant bacteria or fungi).     

Effect of glucose on the distribution of iodine-123-IHA-16 between esterification and oxidation in canine myocardium

To evaluate the effect of glucose perfusion on the myocardial metabolism of [123I]-16-iodo-9-hexadecenoic acid (IHA), the latter was injected intravenously into six fasting dogs perfused with a solution lacking glucose (controls) and seven fasting dogs perfused with glucose and insulin. The distribution of myocardial 123I among iodides, free IHA, and esterified IHA was measured in myocardial biopsy specimens. The increase in esterification and decrease in oxidation of IHA due to glucose were quantified using a compartmental mathematical model of myocardial IHA metabolism. Subsequently, in six control and six glucose-perfused dogs, cardiac radioactivity was measured with a scintillation camera for 1 hr following i.v. injection of IHA. Four different methods were used to analyze the myocardial time-activity curves and to calculate the distribution of IHA between oxidation and esterification. Results comparable to those provided by analysis of biopsy specimens can be obtained by considering the curve to be the sum of an exponential and a constant, or by analyzing it with a compartmental mathematical model.