Specific mutations in the enhancer II/core promoter/precore regions of hepatitis B virus subgenotype C2 in Korean patients with hepatocellular carcinoma

Recently, hepatitis B virus (HBV) genotypes and mutations have been reported to be related to hepatocellular carcinoma (HCC). This cross‐sectional case–control study examined the relationship between HCC and mutations in the enhancer II/core promoter and precore regions of HBV by comparing 135 Korean HCC patients infected with HBV genotype C2 (HBV/C2; HCC group) with 135 age‐, sex‐, and hepatitis B e antigen (HBeAg) status‐matched patients without HCC (non‐ HCC group). Age and sex were also matched between HBeAg‐positive and ‐negative patients. The prevalence of T1653, A1689, V1753, T1762/A1764, T1846, A1850, C1858, and A1896 mutations was evaluated in this population. The prevalence of the T1653 mutation in the box α region, the A1689 mutation in between the box α and β regions, and the T1762/A1764 mutations in the basal core promoter region was significantly higher in the HCC group compared to the non‐HCC group (8.9% vs. 2.2%, P = 0.017; 19.3% vs. 4.4%, P < 0.001; and 60.7% vs. 22.2%; P < 0.001). Among HBeAg‐negative patients, the frequency of the T1653 mutation was higher in the HCC group. Regardless of HBeAg status, the prevalence of the A1689, and T1762/A1764 mutations was higher in the HCC group than in the non‐HCC group. However, no association was observed between mutations in the precore region and HCC. Upon multivariate analysis, the presence of the T1653, A1689, and T1762/A1764 mutations was an independent predictive factor for HCC. The addition of the T1653 or A1689 mutation to T1762/A1764 increased the risk of HCC. In conclusion, the T1653, A1689, and/or T1762/A1764 mutations were associated with the development of HCC in Korean patients infected with HBV/C2. J. Med. Virol. 81:1002–1008, 2009. © 2009 Wiley‐Liss, Inc.     

Raised serum interleukin 15 levels in Kawasaki disease

BACKGROUND: Interleukin (IL)15 is a novel cytokine that induces T cell proliferation, B cell maturation, natural killer cell cytotoxicity, and may have a pivotal role in the pathogenesis of inflammatory disease, acting upstream from tumour necrosis factor alpha (TNFalpha). Kawasaki disease (KD) is an inflammatory disease, in which serum levels of inflammatory cytokines such as TNFalpha and IL6 are increased. OBJECTIVE: To examine the serum levels of IL15 in KD and to evaluate the role of IL15 in estimating the severity of inflammation in KD. Results and conclusion: There was a significant increase in the mean (SD) serum levels of IL15 measured in the acute stage of KD (11.5 (5.8) pg/ml) compared with those in the subacute stage (1.3 (0.9) pg/ml) (p<0.01) and normal controls (0.9 (1.0) pg/ml) (p<0.01). The increase in IL15 correlated with the increase in TNFalpha (r(s)=0.66, p<0.01); however it did not correlate with the levels of erythrocyte sedimentation rate and C reactive protein, suggesting that IL15 may not be a useful marker in estimating the severity of inflammation in KD.     

Fabrication of a metal-ceramic crown to fit an existing partial removable dental prosthesis using ceramic pressed to metal technique: a clinical report

Fabricating a crown to retrofit an existing abutment tooth for a partial removable dental prosthesis (PRDP) is one of the most time-consuming and labor-intensive clinical procedures. In particular, when the patient is concerned with esthetic aspects of restoration, the task of fabricating becomes more daunting. Many techniques for the fabrication of all-metallic or metal-ceramic crowns have been discussed in the literature. This article was aimed to describe a simple fabrication method in which a retrofitting crown was fabricated for a precise fit using a ceramic-pressed-to-metal system.     

Carotid endarterectomy with normal findings from a completion study: Is there need for early duplex scan?

OBJECTIVE: The objective of this study was to determine the value of early (< 6 months) duplex scanning after carotid endarterectomy (CEA) with an intraoperative completion study with normal results. Attention was paid to restenosis rates and reoperation for recurrent stenosis within the first 6 months. METHODS: A retrospective review was performed on 380 CEAs (338 patients) with intraoperative completion studies and duplex surveillance within the first 6 months. Results of completion studies, restenosis rates, and recurrent symptoms were evaluated for each operation. Studies were performed from 0 to 200 days postoperatively (median, 28). RESULTS: Intraoperative completion studies included 333 angiograms, 26 duplex scans, and 21 angiograms with duplex scans. Of the 380 intraoperative completion studies, 28 (7.5%) had abnormal findings, including 14 abnormal internal carotid arteries (ICAs). Twenty-four procedures were revised, and the findings of all repeat completion studies were normal. Of the initial completion studies, in four cases, abnormalities (3 ICAs) were insignificant and did not warrant further intervention. Follow-up ICA duplex scans had normal results after 364 (95.8%) CEAs. There were 14 mild recurrent ICA stenoses and two moderate recurrent ICA stenoses; neither had abnormal findings from the completion study. There were no severe recurrent ICA stenoses. External carotid artery (ECA) recurrent stenosis included 7 mild, 15 moderate, and 9 severe restenoses. CONCLUSIONS: Only 0.5% of CEAs developed moderate restenosis. No procedures had severe recurrent stenosis on duplex scan within the first 6 months, and none required intervention. Duplex surveillance in the first 6 months is relatively unproductive, providing that there were normal results from an intraoperative completion study for each patient. Routine surveillance can be started at 1 year.     

Three-dimensional analysis of molar compensation in patients with facial asymmetry and mandibular prognathism

Objective:To evaluate the characteristic transverse dental compensations in patients with facial asymmetry and mandibular prognathism and to compare features of dental compensations between two types of mandibular asymmetry using 3-dimensional (3D) cone-beam computed tomography (CBCT).Materials and Methods:Seventy-eight adult patients with skeletal Class I (control group; n  =  33; 19 men and 14 women) or skeletal Class III with facial asymmetry (experimental group; n  =  45; 23 men and 22 women) were included. The experimental group was subdivided into two groups according to the type of mandibular asymmetry: translation type (T-type; n  =  20) and roll type (R-type; n  =  19). CBCT images were acquired before orthodontic treatment and 3D analyses were performed.Results:The transverse dental distance was significantly different between the two groups only at the palatal root apex of the maxillary first molar (P < .05). In the experimental group, the first molar axes were compensated significantly on both arches except the maxillary nondeviated side. The vertical molar heights were different between the two groups only on the maxillary arch (P < .001). The R-type showed greater mandibular ramal length difference and menton deviation than the T-type (P < .001). In the R-type, transverse compensation of the maxillary first molars was more obvious than with the T-type, which resulted in canting in the maxillary occlusal plane.Conclusions:Mandibular asymmetry with prognathism showed a characteristic transverse dental compensation pattern. The mandibular asymmetry type influenced the amount and direction of molar compensation on the maxillary arch.     

Engineering and Visualization of Bacteria for Targeting Infarcted Myocardium

Optimization of the specific affinity of cardiac delivery vector could significantly improve the efficiency of gene/protein delivery, yet no cardiac vectors to date have sufficient target specificity for myocardial infarction (MI). In this study, we explored bacterial tropism for infarcted myocardium based on our previous observations that certain bacteria are capable of targeting the hypoxic regions in solid tumors. Out of several Escherichia coli or Salmonella typhimurium strains, the S. typhimurium defective in the synthesis of ppGpp (ΔppGpp S. typhimurium) revealed accumulation and selective proliferation in the infarcted myocardium without spillover to noncardiac tissue. The Salmonellae that were engineered to express a variant of Renilla luciferase gene (RLuc8), under the control of the E. coli arabinose operon promoter (P_BAD), selectively targeted and delivered RLuc8 in the infarcted myocardium only upon injection of -arabinose. An examination of the infarct size before and after infection, and estimations of C-reactive protein (CRP) and procalcitonin indicated that intravenous injection of ΔppGpp S. typhimurium did not induce serious local or systemic immune reactions. This current proof-of-principle study demonstrates for the first time the capacity of Salmonellae to target infarcted myocardium and to serve as a vehicle for the selective delivery of therapeutic agents in MI.     

Folate receptor targeting silica nanoparticle probe for two-photon fluorescence bioimaging

Narrow dispersity organically modified silica nanoparticles (SiNPs), diameter ~30 nm, entrapping a hydrophobic two-photon absorbing fluorenyl dye, were synthesized by hydrolysis of triethoxyvinylsilane and (3-aminopropyl)triethoxysilane in the nonpolar core of Aerosol-OT micelles. The surface of the SiNPs were functionalized with folic acid, to specifically deliver the probe to folate receptor (FR) over-expressing Hela cells, making these folate two-photon dye-doped SiNPs potential candidates as probes for two-photon fluorescence microscopy (2PFM) bioimaging. In vitro studies using FR over-expressing Hela cells and low FR expressing MG63 cells demonstrated specific cellular uptake of the functionalized nanoparticles. One-photon fluorescence microscopy (1PFM) imaging, 2PFM imaging, and two-photon fluorescence lifetime microscopy (2P-FLIM) imaging of Hela cells incubated with folate-modified two-photon dye-doped SiNPs were demonstrated.     

A new Nav1.7 sodium channel mutation I234T in a child with severe pain

Dominant gain‐of‐function mutations that hyperpolarize activation of the Na_v1.7 sodium channel have been linked to inherited erythromelalgia (IEM), a disorder characterized by severe pain and redness in the feet and hands in response to mild warmth. Pharmacotherapy remains largely ineffective for IEM patients with cooling and avoidance of triggers being the most reliable methods to relieve pain. We now report a 5 year old patient with pain precipitated by warmth, together with redness in her hands and feet. Her pain episodes were first reported at 12 months, and by the age of 15–16 months were triggered by sitting as well as heat. Pain has been severe, inducing self‐mutilation, with limited relief from drug treatment. Our analysis of the patient's genomic DNA identified a novel Na_v1.7 mutation which replaces isoleucine 234 by threonine (I234T) within domain I/S4–S5 linker. Whole‐cell voltage‐clamp analysis shows a I234T‐induced shift of −18 mV in the voltage‐dependence of activation, accelerated time‐to‐peak, slowed deactivation and enhanced responses to slow ramp depolarizations, together with a −21 mV shift in the voltage‐dependence of slow‐inactivation. Our data show that I234T induces the largest activation shift for Na_v1.7 mutations reported thus far. Although enhanced slow‐inactivation may attenuate the gain‐of‐function of the I234T mutation, the shift in activation appears to be dominant, and is consistent with the severe pain symptoms reported in this patient.