Virus receptor trap neutralizes coxsackievirus in experimental murine viral myocarditis

OBJECTIVE: The coxsackie and adenovirus receptor (CAR) and the decay-accelerating factor (DAF) are receptors for coxsackievirus B3 (CVB3), which is known as the major cause of human viral myocarditis. We investigated the potential for therapeutic use of soluble virus receptor fusion proteins. METHODS: We designed and generated a novel virus receptor trap (hCAR-hDAF:Fc) consisting of both CVB3 receptors and the Fc portion of human IgG1 and evaluated its antiviral effects in experimental CVB3 myocarditis. RESULTS: Among four soluble virus receptor fusion proteins (hCAR:Fc, hDAF:Fc, hCAR-hDAF:Fc and hDAF-hCAR:Fc), hCAR:Fc and hCAR-hDAF:Fc in the supernatant of transfected cells neutralized echovirus, adenovirus, and various serotypes of CVB in a dose-dependent manner. Both soluble viral receptor proteins bound to the VP0 and VP1 capsid proteins of CVB3. The in vivo efficacy of viral receptor proteins was evaluated by intramuscular injection of plasmid (hCAR:Fc or hCAR-hDAF:Fc) followed by electroporation in a murine model of CVB3 myocarditis. Serum levels of the virus receptor proteins increased relative to baseline values from day 3 and peaked on day 14 at 12.9-fold for hCAR:Fc and 7.1-fold for hCAR-hDAF:Fc. The 3-week survival rate was significantly higher in hCAR-hDAF:Fc-treated mice (61%) than in hCAR:Fc-treated mice (29%) and in controls (15%; p<0.05). Myocardial inflammation, fibrosis, and myocardial virus titers were all significantly reduced in the hCAR:Fc and hCAR-hDAF:Fc groups compared to the controls. CONCLUSION: Our soluble virus receptor trap, hCAR-hDAF:Fc, attenuated viral infection, myocardial inflammation, and fibrosis, resulting in higher survival rates in mice with coxsackieviral myocarditis. Furthermore, it consists exclusively of human components, and we demonstrated that this soluble virus receptor trap may be used as a potential candidate for a novel therapeutic agent for the treatment of acute viral myocarditis during the viremic phase.     

Is there any role for thoracoscopy in the diagnosis of benign pleural effusions

Thoracoscopy in the endoscopy suite, has a high diagnostic yield of undiagnosed pleural effusions with minimal and mild complications. Whereas relatively minimal invasive techniques, such as thoracentesis, image‐guided pleural biopsy or blind pleural biopsy, can yield sufficient cell or tissue material to establish the diagnosis of the underlying condition, more definite invasive diagnostic and therapeutic procedure, such as thoracoscopy, may be required for accurate sampling and diagnosis, and further provide real‐time treatment options in same procedure. If thoracoscopy is considered the gold standard for the diagnosis is a fact in case. The current review aims to provide informations on thoracoscopy indications in benign pleural diseases according to up to date publications.     

Coronary artery calcification and dietary cholesterol intake in Korean men

OBJECTIVE: This study was performed to examine the relationship between dietary cholesterol intake and coronary artery calcification (CAC) score in healthy men. METHODS: Electron beam computed tomography (EBCT) was used to examine the CAC score in 135 Korean men aged 40-81 years who did not have clinical illness. Dietary cholesterol intake was assessed by a nutritionist using a semiquantitative food frequency method. Body mass index (BMI), serum lipid levels, cigarette use, alcohol intake, exercise, and a past history of cardiovascular disease were determined during interview and examination. RESULTS: The resultant median CAC score among those who experienced CAC was 22.5 (1-697) and average intakes of total fat and cholesterol were 22.4% (13.8-40.7) of total energy intake and 306.0 mg/day (84-1191). When the participants were classified into high (> or = 75 percentile) and low (< 75 percentile) CAC score groups, multiple logistic analysis showed that the cholesterol intake (per 10 mg/1000 kcal of energy) was significantly related to a high CAC score (OR 1.12: 95% CI 1.02-1.24), after adjustment for age, BMI, serum triglyceride level, past history of hypertension, past history of hyperlipidaemia, and energy intake. Also, when participants were classified into 2 groups (CAC score > or = 100 vs. < 100), cholesterol intake was found to be significantly related to CAC score. However, fatty acid intakes were not significantly related to the CAC score. CONCLUSION: These results suggest that in a population with a relatively low risk of coronary heart disease, higher cholesterol intake may increase the level of CAC.     

Determination of the substrate-docking site of protein tyrosine kinase C-terminal Src kinase

Protein tyrosine kinases (PTK) are key enzymes of mammalian signal transduction. For the fidelity of signal transduction, each PTK phosphorylates only one or a few proteins on specific Tyr residues. Substrate specificity is thought to be mediated by PTK-substrate docking interactions and recognition of the phosphorylation site sequence by the kinase active site. However, a substrate-docking site has not been determined on any PTK. C-terminal Src kinase (Csk) is a PTK that specifically phosphorylates Src family kinases on a C-terminal Tyr. In this study, by sequence alignment and site-specific mutagenesis, we located a substrate-docking site on Csk. Mutations in the docking site disabled Csk to phosphorylate, regulate, and complex with Src but only moderately affected its general kinase activity. A peptide mimicking the docking site potently inhibited (IC50 = 21 microM) Csk phosphorylation of Src but only moderately inhibited (IC50 = 422 microM) its general kinase activity. Determination of the substrate-docking site provides the structural basis of substrate specificity in Csk and a model for understanding substrate specificity in other PTKs.     

Characterization of the first Korean isolate of a Chlamydia pneumoniae strain

Chlamydia pneumoniae is a common pathogen that causes upper and lower respiratory tract infections and is difficult to isolate from clinical specimens. Recently, we succeeded in isolating the first C. pneumoniae strain in Korea. This study characterizes the morphology, infectivity, and drug sensitivity of the Korean strain, designated LKK-1. Electron microscopy was performed for thin sections, and the infectivity over time was tested by counting the inclusion-forming units every 12 h. The minimum inhibitory concentrations of doxycycline, erythromycin, clarithromycin, ciprofloxacin, and levofloxacin were determined following the standard Japanese method. The elementary bodies of LKK-1 were round, like those in Japanese strain KKpn-1, whereas those of TW-183 have wavy cell membranes and are pear-shaped. The infectivity curve and drug sensitivities of LKK-1 were nearly the same as those of KKpn-1. In conclusion, LKK-1, the first strain from Korea, is similar to the Japanese strain KKpn-1 in terms of morphology, growth, and drug sensitivities, and shows a distinct difference in morphology compared with TW-183. Further studies are needed to elucidate the morphological differences between round strains and classical pear-shaped strains of C. pneumoniae.     

Introduction of HIV type 1 subtype E virus into South Korea

Subtype E HIV-1 is the most prevalent strain in Southeast Asia. Although subtype B is prevalent in Korea, geographical distance and increases in travel may lead to the spread of subtype E in Korea. Therefore, we tried to identify and monitor the patterns of HIV subtype E virus introduction into Korea. The divergence of nucleotide sequences within the envelope region (V3 to V5) of Korean subtype E isolates ranged from 4.3 to 14.6% (n = 8; mean, 9.5 +/- 2.8%). In pairwise comparisons of subtype E isolates between Korea and other regions, the divergence of nucleotide sequences between 8 Korean and 16 Asian subtype E variants ranged from 1.3 to 15.2% (mean, 7.8 +/- 2.6%), whereas the divergence of nucleotide sequences between 8 Korean and 2 African variants ranged from 11.7 to 20.7% (mean, 15.4 +/- 2.2%). A phylogenetic tree showed that Korean subtype E isolates cluster with the Asian isolates but far from the African isolates. These epidemiological and molecular epidemiological data suggest that HIV-1 subtype E strains have been transmitted into Korea from endemic areas of Southeast Asia rather from Africa.