Adult Renal Cell Carcinoma: A Review of Established Entities from Morphology to Molecular Genetics

According to the current World Health Organization (WHO), renal cell carcinomas (RCCs) that primarily affect adults are classified into 8 major subtypes. Additional emerging entities in renal neoplasia have also been recently recognized and these are discussed in further detail by Mehra et al (Emerging Entities in Renal Neoplasia, Surgical Pathology Clinics, 2015, Volume 8, Issue 4). In most cases, the diagnosis of a RCC subtype can be based on morphologic criteria, but in some circumstances the use of ancillary studies can aid in the diagnosis. This review discusses the morphologic, genetic, and molecular findings in RCCs previously recognized by the WHO, and provides clues to distinction from each other and some of the newer subtypes of RCC. As prognosis and therapeutic options vary for the different subtypes of RCC, accurate pathologic distinction is critical for patient care.     

B cell antigen receptor cross-linking induces tyrosine phosphorylation and membrane translocation of a multimeric Shc complex that is augmented by CD19 co-ligation

The SH2 domain-containing transforming Shc protein has been implicated in mitogenic signaling via several surface receptors through p21^ras. Following tyrosine phosphorylation by either receptor or non-receptor tyrosine kinases, Shc may interact with the adaptor protein Grb2, which is linked to Sos1, a guanine nucleotide exchange factor for human ras. Ligation of the antigen receptor complex on B cells (BCR) is known to activate various intracellular signaling pathways, which may accumulate in mitogenic responses. With respect to the initial steps, the activation of BCR-associated non-receptor tyrosine kinases appears to be indispensible. In this report we show that Shc proteins become tyrosine phosphorylated after BCR ligation on both transformed and normal human B cells. This is accompanied by the association of Shc with Grb2 proteins and a yet unidentified 145-kDa tyrosine phosphorylated protein. Subcellular fractionation revealed that this activation-induced multimeric Shc complex rapidly translocates towards the plasma membrane. Co-ligation of the BCR with the CD19 molecule results in a marked increase of these events, whereas CD19 cross-linking alone does not induce Shc tyrosine phosphorylation or translocation. Thus, in B cells the Shc complex may represent a molecular junction between the BCR and the mitogenic p21^ras cascade.     

Genetic analysis of the formation of the Ysc-Yop translocation pore in macrophages by Yersinia enterocolitica: role of LcrV, YscF and YopN

The Ysc-Yop type III secretion (TTS) system allows extracellular Yersinia bacteria, adhering to eukaryotic target cells, to inject Yop effector proteins in the cytosol of these cells. The secretion apparatus, called the injectisome, ends up with a needle-like structure made of YscF. YopN, one of the proteins secreted by the injectisome is thought to act as a plug. YopB, YopD and LcrV, three other proteins secreted by the injectisome and called 'translocators' form a pore allowing translocation of the Yop effectors across the target cell plasma membrane. Here, we tested the role of LcrV, YscF and YopN in the formation of this pore in macrophages by monitoring the release of the low-molecular-weight fluorescent dye BCECF (2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein, acetoxymethyl ester, 623Da) and of the high-molecular-weight lactate dehydrogenase (LDH, 135 kDa). BCECF is released through the translocation pore itself provided no Yop effector is trafficking through the channel. In contrast, LDH is released by the osmotic lysis of the target cell that occurs after pore formation. This release is reduced by the GAP activity of YopE. In order to study the role of LcrV, one has to circumvent the regulatory effect of LcrV on the synthesis of YopB and YopD. We observed here that this regulatory role of LcrV is lost in a yopQ mutant and hence we studied the role of LcrV in a yopQ mutant background. A lcrV, yopQ double mutant was deficient in pore formation while able to produce YopB and YopD. Pore formation was restored by the introduction of lcrV(+) but not yopQ(+) confirming that LcrV itself is directly required for pore formation. Bacteria secreting only YopB, YopD and LcrV could form pores, showing that YopB, YopD and LcrV are sufficient for pore formation provided they are secreted by the same bacterium. LcrV is not involved in secretion of YopB and YopD as suggested previously. Bacteria producing normal Ysc injectisomes, including the YscF needle but no translocators did not form pores, indicating that the needle is not sufficient by itself for pore formation, as was also suggested. yopN mutant bacteria formed needles and released BCECF even if they secreted the effectors. This observation suggests that many translocation pores are not filled in the absence of YopN and thus that YopN might form a link between the needle and the pore, guiding the effectors.     

Monosomy 9q and trisomy 16q in a case of congenital solitary infantile myofibromatosis

Although infantile myofibromatosis (IM) is the most common fibrous proliferation of infancy, many aspects of this benign lesion have not been explored. IM histogenesis is still poorly understood, despite immunohistochemical staining and ultrastructural features that suggest a myofibroblastic origin. IM diagnosis is often made difficult by the predominance of small primitive spindle cells over myofibrobasts and the presence of intravascular growth. Genetic information is scarce, with only one karyotyped case. Here we describe a case of solitary IM discovered at birth in an otherwise healthy girl. The tumor was well circumscribed, arranged in nodules and made up of ovoid cells without atypia, in a myxoid background. Immunohistochemical evaluation indicated a myofibroblastic differentiation. The cytogenetic and fluorescence in situ hybridization analyses revealed an abnormal chromosome 9, derived from an unbalanced whole-arm translocation between chromosomes 9 and 16. On both chromosomes, the breakpoints were located in the pericentric heterochromatic region. This clonal abnormality has not been reported in other tumors and is different from the chromosome 6q deletion reported in the single previous reported IM karyotype.     

胸腺肽对肠梗阻细菌移位的影响

目的：通过对大鼠机械性肠梗阻模型细菌移位的实验研究,了解应用胸腺肽后,大鼠肠梗阻致细菌移位的改变情况,探索减少细菌移位的可能药物。方法：雄性ＳＤ大鼠３０只,随机分为假手术组,肠梗阻组和胸腺肽组。检测肝脏和肠系膜淋巴细菌移位情况、血浆内毒素水平和进行回肠病理学检查等。结果：细胞移位率和细菌移位数水平,肠梗阻组和假手术组相比,明显升高,胸朱肽组和肠阻组相一少,血浆内毒素水平,胸腺肽组与肠梗阻组相比明显     

Mapping translocation breakpoints by orthogonal field agarose-gel electrophoresis

Orthogonal field agarose-gel electrophoresis (OFAGE) of chromosomes from translocation-bearing and normalNeurospora crassa strains was utilized, first, to recover cosmids from a translocated region, and second, to map translocation breakpoints. Surprisingly, the right breakpoints in two independently derived, interstitial translocations,T(II III) AR18 andT(II VI)P2869, are within about 5.6 kbp of each other suggesting that this region of linkage group (LG) II may be fragile or otherwise subject to chromosome breakage. Mapping translocation breakpoints through OFAGE, or other similar methods, should allow for DNA sequencing across breakpoints that are not associated with mutant phenotypes or that are not within walking distance of cloned markers.     

腰痹舒治疗腰椎间盘突出症临床疗效分析

用中药腰痹舒治疗腰椎间盘突出症 3 1例 ,治愈 2 8例 ,有效 3例。治疗后随访 6～ 1 8个月 ,无 1例复发。与牵引、按摩、秋水仙碱内服对照组比较 ,中药疗效显著优于对照组 (P<0 .0 5 )。经 CT检查 ,腰痹舒治愈后椎间盘的后突压迫、粘连均有不同程度的解除。提出可根据症状、体征将腰椎间盘出症的腰腿痛分为 1 0级。作为判断病情和疗程的主要指标。其治疗宜通经、化瘀散寒为主。     

Clinical research in small genomically stratified patient populations

The paradigm of early drug development in cancer is shifting from ‘histology-oriented’ to ‘molecularly oriented’ clinical trials. This change can be attributed to the vast amount of tumour biology knowledge generated by large international research initiatives such as The Cancer Genome Atlas (TCGA) and the use of next generation sequencing (NGS) techniques developed in recent years. However, targeting infrequent molecular alterations entails a series of special challenges. The optimal molecular profiling method, the lack of standardised biological thresholds, inter- and intra-tumor heterogeneity, availability of enough tumour material, correct clinical trials design, attrition rate, logistics or costs are only some of the issues that need to be taken into consideration in clinical research in small genomically stratified patient populations. This article examines the most relevant challenges inherent to clinical research in these populations. Moreover, perspectives from the Academia point of view are reviewed as well as initiatives to be taken in forthcoming years.     

口腔埋伏牙自体移植的临床研究

目的 探讨埋伏牙、易位牙再植的方法和临床疗效.方法 选择埋伏或易位的上前牙18颗,微创拔出错位牙,修整牙槽窝,立即植入牙槽窝内,结扎固定.术后1、2、3、4、5、6、12个月复查再植牙的松动度、牙髓活力、X线片.结果 18颗牙再植术后6个月各项指标正常,临床效果满意.结论 埋伏牙或易位牙可通过拔牙再植的方法恢复正常的咬合关系和咀嚼功能.