Epitope load identifies kidney transplant recipients at risk of allosensitization following minimization of immunosuppression

1. Download : Download high-res image (301KB)
2. Download : Download full-size image

     

Endodontic treatment of a hypertaurodontic mandibular left second molar in a patient with many taurodonts combined with multiple pulp stones

Taurodontism is a rare embryologic anomaly of teeth, defined by an apical displacement of the furcation of roots and enlarged pulp chambers. Taurodontism has been classified as hypo‐, meso‐ or hypertaurodontism according to the severity of the anomaly. The aim of this case report was to illustrate a clinical case with multiple bilateral taurodonts and to describe the endodontic management of the hypertaurodontic mandibular left second molar with a C‐shaped canal and extensive dental pulp calcifications. A healthy 20‐year‐old male patient was referred for the endodontic treatment of his lower left second molar. Cone beam computed tomography revealed a C‐shaped root canal configuration and several dental pulp calcifications in this tooth. The endodontic treatment was performed in two appointments under an operating dental microscope. A panoramic radiograph, made during the 18 months follow‐up appointment, revealed nine other taurodontic molars, most of them associated with dental pulp calcifications.     

Preparation and tumor affinity testing of the radioiodinated tetrahydroisoquinoline derivative [123I]TIC(OH) for targeting prostate cancer.

This work describes the synthesis and tumor affinity testing of 8-[123I]iodo-l-1,2,3,4-tetrahydro-7-hydroxyisoquinoline-3-carboxylic acid [ITIC(OH)], a cyclic non-naturally occurring amino acid as an imaging probe for prostate cancer. Parameters for labelling were optimized with regard to the amount of precursor, the temperature and time. Thereafter, ITIC(OH) was evaluated in terms of its uptake in primary human PC-3 and DU-145 prostate cancer cells, followed by analysis of the underlying mechanisms of the radioactivity accumulation in tumor cells. No-carrier-added ITIC(OH) was obtained in 80+/-15% radiochemical yield and >98% radiochemical purity by a one-step radioiodination, using IODO-GEN as oxidant. The total synthesis time was less than 30 min, and compatible with a clinical routine production. ITIC(OH) accumulated intensively in primary human prostate cancer cells. The radioactivity incorporation in tumor following a 10-min incubation at 37 degrees C/pH 7.4 varied from 35% to 58% of the total loaded activity per 10(6) tumor cells (355-540 cpm/1000 cells). Inhibition experiments revealed that ITIC(OH) was taken up into tumor by an active transport different from the common amino acid carrier systems, including the sodium-dependent system A and B+,0, and the sodium-independent L- and ASC-type transporter. In contrast, the cellular incorporation was dependent on the membrane potential and correlated with the activity of the mitochondria. In conclusion, the specific and high-level accumulation of ITIC(OH) in human prostate carcinoma cells, indicates that the new radiopharmaceutical is a good candidate for further in vivo investigations to ascertain its potential as an imaging probe for prostate cancer by SPET.     

模拟舰船磁场与噪声、高温复合对机体作用的方差分析

目的 研究模拟舰船两种剂量水平磁场复合噪声、高温对机体联合作用的特点。方法 采用有交互作用的三因素二水平的正交试验设计方法及方差分析法，按正交表L8（2^7）的要求安排8种复合暴露剂量组合，分别将兔和大鼠分为8个复合暴露组和8个对照组。结果 兔球结膜毛细血管管径、大鼠肝和脾脏HSP70的分析结果显示出磁场是对其影响的主因素（均为P〈0．01），其次是高温（均为P〈0．05）,大鼠下丘脑AVP和大鼠脑组织HSP70的分析结果显示出磁场是对其影响的主因素（均为P〈0．05）。兔血浆内皮素的分析结果显示出磁场与噪声交互作用所对应的F值有非常显著性意义（P〈0．01），磁场与噪声、高温三者之间交互作用所对应的F值也有显著性意义（P〈0．05）。结论 磁场是对上述指标影响的主因素，而高温也是重要因素；磁场与噪声有交互作用，磁场与噪声、高温三者之间也有交互作用；应该重视舰船环境因素对舰船人员的复合作用。     

复合杂合parkin基因突变家族的不同表型

背景：Parkin基因（PRKN）突变可导致常染色体隐性遗传性早发帕金森病（EOPD）。目的：探讨EOPD白人家族PRKN突变的表现和基因型-表型关系。设计：对EOPD家族的3代20例成员进行基因分析，该家族有4例患者。应用直接基因组DNA测序、半定量聚合酶链反应、实时定量聚合酶链反应以及逆转录酶聚合酶链反应分析以确定PRKN突变。结果：4例早发患者（年龄30—38岁）被确定有PRKN复合杂合突变（T240M和EX5_6缺失），虽然PRKN的杂合T240M和纯合EX5_6缺失突变已有描述，但是据悉，本文为上述复合杂合突变的首次报道。患者的表型为典型常染色体隐性遗传性EOPD的表现，其特征是对左旋多巴治疗有效、相对缓慢的进展和运动障碍。所有杂合突变的基因携带者（T240M或EX5_6缺失）和1例56岁的复合杂合突变女性携带者（T240M和EX5_6缺失）无任何神经系统症状。结论：研究发现，PRKN基因复合杂合突变（T240M和EX5_6缺失）导致一个大的白人家族中4例成员发生常染色体隐性遗传性EOPD。另外1例成员具有相同的突变，比4例患者的平均发病年龄大10岁，并且无本病的临床表现。不完全的外显率对遗传咨询具有暗示作用，并且提示复杂的基因一环境交互作用在PRKN相关EOPD的发病机制中发挥作用。     

Strategies to enhance transductional efficiency of adenoviral-based gene transfer to primary human fibroblasts and keratinocytes as a platform in dermal wounds

Genetically modified keratinocytes and fibroblasts are suitable for delivery of therapeutic genes capable of modifying the wound healing process. However, efficient gene delivery is a prerequisite for successful gene therapy of wounds. Whereas adenoviral vectors (Ads) exhibit superior levels of in vivo gene transfer, their transductional efficiency to cells resident within wounds may nonetheless be suboptimal, due to deficiency of the primary adenovirus receptor, coxsackie-adenovirus receptor (CAR). We explored CAR-independent transduction to fibroblasts and keratinocytes using a panel of CAR-independent fiber-modified Ads to determine enhancement of infectivity. These fiber-modified adenoviral vectors included Ad 3 knob (Ad5/3), canine Ad serotype 2 knob (Ad5CAV-2), RGD (Ad5.RGD), polylysine (Ad5.pK7), or both RGD and polylysine (Ad5.RGD.pK7). To evaluate whether transduction efficiencies of the fiber-modified adenoviral vectors correlated with the expression of their putative receptors on keratinocytes and fibroblasts, we analyzed the mRNA levels of CAR, alpha upsilon integrin, syndecan-1, and glypican-1 using quantitative polymerase chain reaction. Analysis of luciferase and green fluorescent protein transgene expression showed superior transduction efficiency of Ad5.pK7 in keratinocytes and Ad5.RGD.pK7 in fibroblasts. mRNA expression of alpha upsilon integrin, syndecan-1 and glypican-1 was significantly higher in primary fibroblasts than CAR. In keratinocytes, syndecan-1 expression was significantly higher than all the other receptors tested. Significant infectivity enhancement was achieved in keratinocytes and fibroblasts using fiber-modified adenoviral vectors. These strategies to enhance infectivity may help to achieve higher clinical efficacy of wound gene therapy.     

Predictive factors of stroke in patients undergoing coronary bypass grafting: statins are protective.

BACKGROUND: Despite major improvement in surgical techniques and intensive care management, stroke remains one of the most devastating complications of coronary artery bypass grafting (CABG). We aimed to determine factors predicting the occurrence of stroke during CABG. A special interest was focused on preoperative therapies. METHODS: We prospectively enrolled 810 consecutive candidates for CABG alone in a specific database, including all pre- and perioperative data (history, clinical, therapeutic, cardiac catheterization, surgical and intensive care data). Univariate tests and then multiple logistic regression analysis were used to determine independent predictive factors. RESULTS: During the first postoperative month, stroke occurred in 11 cases and transient ischemic attack (TIA) in 4 additive cases (cumulative rate: 1.85%). After the multivariate analysis, the following factors remained significant (p<0.05) in the predictive model, with corresponding odds ratios between brackets: redo cardiac surgery (7.45), unstable cardiac status (4.74), past history of cerebrovascular disease (4.14), past history of peripheral arterial disease (3.55), whereas the presence of preoperative statins was protective (0.24, 95% IC: 0.07-0.78). The addition of perioperative data (aortic calcification, postoperative arrhythmia, on/off-pump surgery) did not change the final predictive model. CONCLUSION: To our knowledge, this is the first real-world observational report highlighting the interest of statins for the prevention of stroke in the very special situation of CABG. Even though according to randomized trials coronary patients have a benefit from these drugs, a special level of interest should be directed towards those presenting the above-mentioned risk factors.