1,016 research outputs found

    Incidence of neurosensory deficits and recovery after lower third molar surgery: a prospective clinical study of 4338 cases

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    A prospective study of all lower third molar surgery performed in the outpatient extraction clinic of a teaching dental hospital was conducted from January 1998 through October 2005 to determine the incidence of subsequent neurosensory deficit due to inferior alveolar nerve (IAN) and lingual nerve (LN) injury, to examine possible contributing risk factors and to describe the pattern of recovery. 3595 patients were included (61% female, 39% male; age range, 14-82 years). Of the 4338 lower third molar extractions performed by various grades of operators, 0.35% developed IAN deficit and 0.69% developed LN deficit. Distoangular impaction was found to increase the risk of LN deficit significantly (p < 0.001). Depth of impaction was related to the risk of IAN deficit (p < 0.001). Undergraduates caused more LN deficits (p < 0.001). Sex, age, raising of a lingual flap, protection of LN with a retractor, removal of distolingual cortex, tooth sectioning and difficulty in tooth elevation were not significantly related to IAN or LN injury. Postoperative recovery from IAN and LN deficits was noted most significantly at 3 and 6 months, respectively. By the end of the follow-up period, 67% of IAN deficits and 72% of LN deficits had recovered completely. Β© 2009 International Association of Oral and Maxillofacial Surgeons.postprin

    Over-expression of miR-106b promotes cell migration and metastasis in hepatocellular carcinoma by activating epithelial-mesenchymal transition process

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    Hepatocellular carcinoma (HCC) is one the the most fatal cancers worldwide. The poor prognosis of HCC is mainly due to the developement of distance metastasis. To investigate the mechanism of metastasis in HCC, an orthotopic HCC metastasis animal model was established. Two sets of primary liver tumor cell lines and corresponding lung metastasis cell lines were generated. In vitro functional analysis demonstrated that the metastatic cell line had higher invasion and migration ability when compared with the primary liver tumor cell line. These cell lines were subjected to microRNA (miRNAs) microarray analysis to identify differentially expressed miRNAs which were associated with the developement of metastasis in vivo. Fifteen human miRNAs, including miR-106b, were differentially expressed in 2 metastatic cell lines compared with the primary tumor cell lines. The clinical significance of miR-106b in 99 HCC clinical samples was studied. The results demonstrated that miR-106b was over-expressed in HCC tumor tissue compared with adjacent non-tumor tissue (p = 0.0005), and overexpression of miR-106b was signficantly correlated with higher tumor grade (p = 0.018). Further functional studies demonstrated that miR-106b could promote cell migration and stress fiber formation by over-expressing RhoGTPases, RhoA and RhoC. In vivo functional studies also showed that over-expression of miR-106b promoted HCC metastasis. These effects were related to the activation of the epithelial-mesenchymal transition (EMT) process. Our results suggested that miR-106b expression contributed to HCC metastasis by activating the EMT process promoting cell migration in vitro and metastasis in vivo. Β© 2013 Yau et al.published_or_final_versio

    Proceedings of The First Current Topic in Infectious Diseases: Consensus Meeting on Conjugate Vaccines of the Center of Infection

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    Titles include: 1. Invasive Haemophilus Influenzae b Disease: Overview and Disease Burden in Hong Kong (YL LAU) ; 2. Overview and Disease Burden of Haemophilus Influenzae Type b in China (YH YANG) ; 3. Factors to Consider in the Routine Use of Hib in Hong Kong (THF TSANG) ; 4. Burden of Pneumococcal Disease in Hong Kong (CB CHOW) ; 5. Overview and Disease Burden of Streptococcus Pneumoniae in China (YH YANG) ; 6. Resistance in Pediatric Isolates of Pneumococci. Results from a Territorywide Carriage Study (SSS CHIU) ; 7. Serotype Distribution of Invasive and Noninvasive Strains of Pneumococci in Hong Kong (PL HO) ; 8. Overview of Conjugate Pneumococcal Vaccine: Serotype Coverage, Efficacy and Status of Usage in other Countries (SSY WONG)Conference Theme: The First Current Topic in Infectious Diseasespublished_or_final_versio

    Microparticle-mediated transfer of the viral receptors CAR and CD46, and the CFTR channel in a CHO cell model confers new functions to target cells

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    Cell microparticles (MPs) released in the extracellular milieu can embark plasma membrane and intracellular components which are specific of their cellular origin, and transfer them to target cells. The MP-mediated, cell-to-cell transfer of three human membrane glycoproteins of different degrees of complexity was investigated in the present study, using a CHO cell model system. We first tested the delivery of CAR and CD46, two monospanins which act as adenovirus receptors, to target CHO cells. CHO cells lack CAR and CD46, high affinity receptors for human adenovirus serotype 5 (HAdV5), and serotype 35 (HAdV35), respectively. We found that MPs derived from CHO cells (MP-donor cells) constitutively expressing CAR (MP-CAR) or CD46 (MP-CD46) were able to transfer CAR and CD46 to target CHO cells, and conferred selective permissiveness to HAdV5 and HAdV35. In addition, target CHO cells incubated with MP-CD46 acquired the CD46-associated function in complement regulation. We also explored the MP-mediated delivery of a dodecaspanin membrane glycoprotein, the CFTR to target CHO cells. CFTR functions as a chloride channel in human cells and is implicated in the genetic disease cystic fibrosis. Target CHO cells incubated with MPs produced by CHO cells constitutively expressing GFP-tagged CFTR (MP-GFP-CFTR) were found to gain a new cellular function, the chloride channel activity associated to CFTR. Time-course analysis of the appearance of GFP-CFTR in target cells suggested that MPs could achieve the delivery of CFTR to target cells via two mechanisms: the transfer of mature, membrane-inserted CFTR glycoprotein, and the transfer of CFTR-encoding mRNA. These results confirmed that cell-derived MPs represent a new class of promising therapeutic vehicles for the delivery of bioactive macromolecules, proteins or mRNAs, the latter exerting the desired therapeutic effect in target cells via de novo synthesis of their encoded proteins

    Determining the neurotransmitter concentration profile at active synapses

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    Establishing the temporal and concentration profiles of neurotransmitters during synaptic release is an essential step towards understanding the basic properties of inter-neuronal communication in the central nervous system. A variety of ingenious attempts has been made to gain insights into this process, but the general inaccessibility of central synapses, intrinsic limitations of the techniques used, and natural variety of different synaptic environments have hindered a comprehensive description of this fundamental phenomenon. Here, we describe a number of experimental and theoretical findings that has been instrumental for advancing our knowledge of various features of neurotransmitter release, as well as newly developed tools that could overcome some limits of traditional pharmacological approaches and bring new impetus to the description of the complex mechanisms of synaptic transmission

    Functional Promoter -31G>C Variant in Survivin Gene Is Associated with Risk and Progression of Renal Cell Cancer in a Chinese Population

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    BACKGROUND: Survivin is an inhibitor of apoptosis protein and is involved in the occurrence and progression of human malignancies. Recently, a functional polymorphism (-31G>C, rs9904341) in the promoter of survivin has been shown to influence its expression and confer susceptibility to different types of cancer. The present study was aimed to investigate whether the polymorphism also influences susceptibility and progression of renal cell cancer (RCC) in a Chinese population. METHODS: We genotyped this polymorphism using the TaqMan assay in a case-control study comprised of 710 RCC patients and 760 controls. The logistic regression was used to assess the genetic association with occurrence and progression of RCC. RESULTS: Compared with the genotypes containing G allele (GG and GC), we found a statistically significant increased occurrence of RCC associated with the CC genotype [Pβ€Š=β€Š0.006, adjusted odds ratio (OR)β€Š=β€Š1.38, 95% confidence interval (CI)β€Š=β€Š1.08-1.76]. The polymorphism was associated with risk of developing advanced stage (ORβ€Š=β€Š2.02, 95%CIβ€Š=β€Š1.34-3.07) and moderately differentiated (ORβ€Š=β€Š1.75; 95%CIβ€Š=β€Š1.20-2.54) RCC. Furthermore, the patients carrying the CC genotype had a significantly greater prevalence of high clinical stage disease (P(trend)β€Š=β€Š0.003). Similar results were also observed when we restricted the analysis to clear cell RCC, a major histological type of RCC. CONCLUSIONS: Our results suggest that the functional -31G>C polymorphism in the promoter of survivin may influence the susceptibility and progression of RCC in the Chinese population. Large population-based prospective studies are required to validate our findings

    Dynamic phenotypic heterogeneity and the evolution of multiple RNA subtypes in Hepatocellular Carcinoma: the PLANET study

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    Intra-tumor heterogeneity (ITH) is a key challenge in cancer treatment, but previous studies have focused mainly on the genomic alterations without exploring phenotypic (transcriptomic and immune) heterogeneity. Using one of the largest prospective surgical cohorts for Hepatocellular Carcinoma (HCC) with multi-region sampling, we sequenced whole genomes and paired transcriptomes from 67 HCC patients (331 samples). We found that while genomic ITH was rather constant across TNM stages, phenotypic ITH had a very different trajectory and quickly diversified in stage II patients. Most strikingly, 30% patients were found to contain more than one transcriptomic subtype within a single tumor. Such phenotypic ITH was found to be much more informative in predicting patient survival than genomic ITH and explains the poor efficacy of single-target systemic therapies in HCC. Taken together, we not only revealed an unprecedentedly dynamic landscape of phenotypic heterogeneity in HCC, but also highlighted the importance of studying phenotypic evolution across cancer types

    Transformation and scattering activities of the receptor tyrosine kinase RON/Stk in rodent fibroblasts and lack of regulation by the jaagsiekte sheep retrovirus receptor, Hyal2

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    BACKGROUND: The envelope (Env) protein of jaagsiekte sheep retrovirus (JSRV) can transform cells in culture and is likely to be the main factor responsible for lung cancer induction by JSRV in animals. A recent report indicates that the epithelial-cell transforming activity of JSRV Env depends on activation of the cell-surface receptor tyrosine kinase Mst1r (called RON for the human and Stk for the rodent orthologs). In the immortalized line of human epithelial cells used (BEAS-2B cells), the virus receptor Hyal2 was found to bind to and suppress the activity of RON. When Env was expressed it bound to Hyal2 causing its degradation, release of RON activity from Hyal2 suppression, and activation of pathways resulting in cell transformation. METHODS: Due to difficulty with reproducibility of the transformation assay in BEAS-2B cells, we have used more tractable rodent fibroblast models to further study Hyal2 modulation of RON/Stk transforming activity and potential effects of Hyal2 on RON/Stk activation by its natural ligand, macrophage stimulating protein (MSP). RESULTS: We did not detect transformation of NIH 3T3 cells by plasmids expressing RON or Stk, but did detect transformation of 208F rat fibroblasts by these plasmids at a very low rate. We were able to isolate 208F cell clones that expressed RON or Stk and that showed changes in morphology indicative of transformation. The parental 208F cells did not respond to MSP but 208F cells expressing RON or Stk showed obvious increases in scattering/transformation in response to MSP. Human Hyal2 had no effect on the basal or MSP-induced phenotypes of RON-expressing 208F cells, and human, mouse or rat Hyal2 had no effect on the basal or MSP-induced phenotypes of Stk-expressing 208F cells. CONCLUSIONS: We have shown that RON or Stk expression in 208F rat fibroblasts results in a transformed phenotype that is enhanced by addition of the natural ligand for these proteins, MSP. Hyal2 does not directly modulate the basal or MSP-induced RON/Stk activity, although it is possible that adaptor proteins might mediate such signaling in other cell types
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