G2019S LRRK2 mutation in familial and sporadic Parkinson's disease in Russia.

Among mutations associated with autosomal dominant and sporadic Parkinson's disease (PD) the G2019S substitution in the leucine-rich repeat kinase 2 (LRRK2) gene is the most frequently identified. To estimate its frequency in Russia, we analyzed 208 patients with PD from the Northwestern region of Russia. Of these, 51 patients were probands from families with PD compatible with autosomal dominant inheritance. The control group represented 161 subjects without neurological disorders settled in the same region. The frequency of the G2019S mutation was greater in familial PD (2 [3.9%] of 51) than in sporadic PD (1 [0.6%] of 157). In addition, this mutation was found in the proband's father, who also had PD, in 1 PD family, and in 1 carrier without signs of PD at age 40 in another PD family. All carriers were heterozygous for the G2019S mutation and reported the Ashkenazi Jewish origin. The mutation was not found in the control group.     

Imaging of thoracic aortic dissection

Acute thoracic aortic dissection has a high mortality if untreated, so the diagnosis must be rapidly made if mortality is to be lowered significantly. Multiple imaging techniques are often used. This retrospective study from 1988 to 1993 assesses the usefulness in diagnosis of chest X-rays, computed tomography (CT) scanning, aortography, magnetic resonance imaging (MRI), trans-thoracic (TTE) and trans-oesophageal (TOE) echocardiography. Forty-two patients with a final clinical diagnosis of dissection were studied. The diagnosis was confirmed in 16 (13 at surgery and three at autopsy). Three died with dissection given as the only cause for death. Chest X-ray abnormalities were seen in all 19 patients with surgery or death from dissection, with a widened mediastinum and/or dilated aorta being present in 17. In the group of 16 patients with surgery or autopsy proof, CT scans found dissections in 9 of 12 patients studied and correctly classified the type in only five. Aortography was performed in five, with accurate depiction of dissection and type in all. TTE found dissections in three of eight patients imaged by this method. MRI and TOE were performed each on two patients, with accurate depiction of dissection and type in each. Because of the relatively low sensitivity of CT scanning in defining aortic dissections Westmead Hospital is currently assessing the use of TOE as the prime imaging modality prior to surgical intervention.     

带股骨大粗隆稳定钢板的动力髋螺钉在不稳定型股骨粗隆间骨折

不稳定型股骨粗隆部骨折采用动力髋螺钉（DHS）固定效果欠佳，术后可出现骨折再移位、内固定松动、并发髋内翻畸形等.自2003年7月-2005年12月，采用DHS加TSP（股骨大粗隆稳定钢板），对32例不稳定型股骨粗隆部骨折进行了手术治疗，临床效果满意，现报告如下。     

Molecular mechanisms accounting for fibrinogen deficiency: from large deletions to intracellular retention of misfolded proteins

Summary.  Fibrinogen, the soluble precursor of fibrin, which is the main protein constituent of the blood clot, is synthesized in hepatocytes in the form of a hexamer composed of two sets of three polypeptides (Aα, Bβ, and γ). Each polypeptide is encoded by a distinct gene, FGA, FGB and FGG , all three clustered in a region of 50 kb on 4q32. Congenital afibrinogenemia is characterized by the complete absence of fibrinogen. The first causative mutation for this disease was identified in Geneva in a non-consanguineous Swiss family in 1999: the four patients were homozygous for a large deletion in the fibrinogen cluster, which eliminated almost the entire FGA genomic sequence. Mutations in the fibrinogen genes may lead to deficiency of fibrinogen by several mechanisms: acting at the DNA level, at the RNA level by affecting mRNA splicing or stability, or at the protein level by affecting protein synthesis, assembly or secretion. Recent reviews have provided helpful updates for the rapidly growing number of causative mutations identified in patients with fibrinogen deficiencies, either afibrinogenemia or hypofibrinogenemia. The aim of this review is to highlight specifically the subset of mutations that allow fibrinogen chain synthesis and hexamer assembly but impair secretion. Indeed, functional studies of these mutations have shed light on the specific sequences and structures in the fibrinogen molecule involved in the quality control of fibrinogen secretion.     

Photoacoustic and ultrasound imaging using dual contrast perfluorocarbon nanodroplets triggered by laser pulses at 1064 nm

Recently, a dual photoacoustic and ultrasound contrast agent—named photoacoustic nanodroplet—has been introduced. Photoacoustic nanodroplets consist of a perfluorocarbon core, surfactant shell, and encapsulated photoabsorber. Upon pulsed laser irradiation the perfluorocarbon converts to gas, inducing a photoacoustic signal from vaporization and subsequent ultrasound contrast from the resulting gas microbubbles. In this work we synthesize nanodroplets which encapsulate gold nanorods with a peak absorption near 1064 nm. Such nanodroplets are optimal for extended photoacoustic imaging depth and contrast, safety and system cost. We characterized the nanodroplets for optical absorption, image contrast and vaporization threshold. We then imaged the particles in an ex vivo porcine tissue sample, reporting contrast enhancement in a biological environment. These 1064 nm triggerable photoacoustic nanodroplets are a robust biomedical tool to enhance image contrast at clinically relevant depths.OCIS codes: (110.5120) Photoacoustic imaging, (170.7170) Ultrasound, (160.4236) Nanomaterials, (170.3880) Medical and biological imaging, (170.7180) Ultrasound diagnostics     

AG825对乳腺癌细胞的辐射增敏作用

目的：通过体外实验观察酪氨酸蛋白激酶抑制剂AG825对人类表皮生长因子受体2（ERBB-2）高表达乳腺癌细胞的生长抑制作用和辐射增敏作用，并从DNA双链断裂（Double strand break，DSB）损伤修复的角度初步探讨AG825辐射增敏机制。方法：首先通过MTT比色法观察了不同浓度AG825对ERBB-2高表达乳腺癌细胞系MDA—MB-453生长抑制作用。然后将细胞设为空白对照组，单纯放射组，AG825预处理组。通过克隆形成实验观察AG825预处理组和单纯辐射组乳腺癌细胞辐射后生存分数（Survivial fraction，SF）的差异。并且通过单细胞中性凝胶电泳分析了AG825预处理对辐射诱导的DSB的影响。同时用免疫印记法分析AG825预处理后MDA—MB-453细胞在辐射后不同时间DSB修复的关键激酶DNA依赖蛋白激酶催化亚单位（DNA dependent protein kinase catalytic subunit，DNA—PKcs）蛋白的表达情况。结果：MTT比色法显示AG825对MDA—MB-453生长抑制作用随AG825浓度增高而增加。辐射后单纯放射组MDA—MB-453细胞生存分数较空白对照组明显下降。AG825预处理组辐射后生存分数较单纯放射组进一步下降，同时DSB较单纯放射组增加。免疫印记显示单纯放射组DNA—PKcs蛋白表迭在辐射后较空白对照组增加，而AG825预处理组DNA—PKcs表达较单纯放射组下降。结论：AG825对ERBB2高表达乳腺癌细胞具有生长抑制作用一、并且其对ERBB2高表达乳腺癌细胞具有辐射增敏作用，其辐射增敏机制可能与AG825抑制DNA—PKes蛋白表达而减少辐射后DSB修复有关。但还需进一步的体内实验来评价AG825辐射增敏作用。     

Staging deep venous thrombosis using ultrasound elasticity imaging: animal model

Deep venous thrombi undergo progressive hardening with age. However, the evolution rate remains poorly characterized by both invasive and noninvasive techniques. In a previous study (Emelianov et al. 2002), we demonstrated the potential of ultrasound elasticity imaging to noninvasively detect and age thrombus using a rat-based model. Knowing that thrombi harden over time is useful, but the value of the technique relies on whether the age of a thrombus can be predicted from strain estimates, and how accurate these predictions are. The objective of the present study is to answer these two questions. In the previous study, thrombus elasticity changes were monitored only on day 3, 6 and 9 after surgically induced formation of thrombosis in rat inferior vena cavas. In this study, ultrasound elasticity imaging was performed on two independent groups of rats (16 in total) starting from day 3 through day 10 with more temporal samples through the thrombus maturation process. For each rat, thrombus hardness was quantified at each scan interval by measures of normalized strains and reconstructed relative Young's moduli. In both groups, strain magnitudes exhibit progressive decrease as clots age. The relationship between the normalized strain and the clot age was developed from the first group and evaluated by the second group. Statistical analysis showed that the age estimation accuracy is within 0.8 day. If further research can successfully transfer the animal clot-hardening model to human patients, we believe that elasticity imaging will become a key component of venous compression ultrasound for effective diagnosis and treatment of deep venous thrombosis.