Human Cytomegalovirus Induces Intercellular Adhesion Molecule-1 Expression in a Monocytic Cell Line, THP-1

It has been reported that inflammatory diseases such as pneumonitis, retinitis, and hepatitis are associated with human cytomegalovirus (HCMV). Intercellular adhesion molecule (ICAM)-1 is an important inflammatory mediator, helping monocytes adhere to endothelial cells when tissues are infected by pathogen including the HCMV. However, little is known about the mechanism of ICAM-1 stimulation by the HCMV infection in monocytes. In this study, a monocytic cell line THP-1 was used to understand ICAM-1 expression by the HCMV infection. Flow cytometric analyses demonstrated that ICAM-1 was stimulated by the HCMV in THP-1 cells with maximum at 24 hours post infection. The stimulated ICAM-1 expression was dependent on the amount of input virus. In order to understand the mechanism of ICAM-1 stimulation during the HCMV infection, cells were treated with specific inhibitors of key elements in inflammation: NF-kappaB inhibitor PDTC, cyclooxygenase 2 inhibitor NS398, and MEK inhibitor PD98059. Flow cytometric analyses revealed that ICAM-1 expression was decreased when treated with PDTC, but not with NS398 or PD98059. Thus, it is suggested that HCMV-induced ICAM-1 expression in THP-1 cells is associates with NF-kappaB.

Comparison of Consensus Sequences and Ancestor Sequences of HIV-1 nef and vif Genes for Development of Korean-Specfic HIV-1 Vaccine

There have been attempts to use consensus sequences or ancestor sequences for development vaccines against viruses with high diversity and variation. In this study, we generated and compared consensus sequences and ancestor sequences of nef and vif genes of HIV-1 isolated from Koreans. Phylogenetic analyses revealed that majorities of the Korean isolates were clustered to form the Korean clade within subtype B (KcB) where foreign isolates were not included. Consensus sequences inferred from the KcB as well as from all Korean isolates were almost identical but significantly different from subtype B consensus sequence or HIV-1 consensus sequence. The genetic distances from one of the Korean isolates to the other Korean isolates were much longer than to the consensus or ancestor sequences deduced from Korean isolates but similar to those of subtype B or HIV-1. Moreover, the genetic distances from the Korean isolates to the consensus sequences were shorter than to the ancestor sequences both in nef and vif genes. Thus, the consensus sequences may be useful in developing Korean-specific HIV-1 vaccine.

A Case of Diabetic Uremic Encephalopathy with Symmetric MR signal Changes in the Basal Ganglia

Acute changes of the bilateral basal ganglia shown in the brain MRI a diabetic uremic patient have been rarely reported. We report a 52-year-old diabetic uremic patient who had neurological disturbances. At admission, axial diffusion-weighted images and T2-weighted images showed high signal intensities in the bilateral basal ganglia, and axial T1-weighted images visualized low signal intensities in same area. The underlying mechanism may be associated with metabolic as well as vascular factors.

Effect of Human Cytomegalovirus on Human Monocyte-derived Dendritic Cells

Dendritic cells (DCs) are potent antigen-presenting cells and generated from diverse sources including monocytes which are known to be the sites for human cytomegalovirus (HCMV) latency. HCMV has been known to suppress or evade from immune functions involving monocytes and DC. Thus, it was attempted to investigate the effect of HCMV infection on the differentiation of DCs from monocytes. Monocytes were prepared from peripheral blood mononuclear cells and they expressed high levels of CD14, CD11a, CD11b, CD11c and HLA molecules, while they did not express lymphocyte-specific CD molecules. The surface expressions of CD molecules and HLA in immature DCs (imDCs) differentiated from HCMV-infected monocytes differed from those in uninfected imDCs. Specifically, the expressions of CD11a, CD11b, CD11c, CD40 and HLA-DR were decreased compared to uninfected imDCs, while CD80 expression was increased in imDCs differentiated from HCMV-infected monocytes. DCs were allowed to mature (mDCs) by treating imDCs with interferon gamma and LPS. When HCMV-infected imDCs were differentiated to mDCs, the expression of mDC-specific CD83 as well as HLA molecules were decreased. Thus, our results suggest that HCMV inhibits phenotytpic differentiation of DCs.

Effect of Antiepileptic Drugs on Bone Mineral Density and Bone Metabolism in Epileptic Patients

BACKGROUND: Bone mineral density (BMD) is influenced by genetic, hormonal, and environmental factors. Long-term antiepileptic drug (AED) use also causes osteopenia or osteoporosis that have been most extensively described in institutionalized patients. But, the mechanism of these abnormalities is unclear. The objective of this study is to determine the effect of AED on bone density and to explain the pathophysiologic mechanisms by analyzing bone related factors. METHODS: We prospectively examined BMD by dual-energy X-ray absorptiometry in 45 patients with epilepsy. We measured the serum calcium, phosphorus, protein, alkaline phosphatase (ALP), bone specific ALP, vitamin D and osteocalcin to analyze the factors that influence bone metabolism. RESULTS: BMD was significantly lower in the patient group than in the control group (p<0.05). 13% of patients had osteopenia and 3% of patients had osteoporosis. The level of bone specific ALP was higher in the patient group, but the level of vitamin D was not different, implying that BMD is decreased by the direct effect of antiepileptic drugs. There was a weak negative correlation and marginal significance between BMD and the duration of therapy in the patient group (r=-0.407, p<0.05). CONCLUSIONS: Long-term antiepileptic drug therapy in patients who have seizures causes significant bone loss in the lumbar spine even in the absence of vitamin D deficiency. In addition, the degree of bone mineral density was weakly related with the therapeutic duration of antiepileptic drugs. The regular evaluation of BMD in patients with long-term antiepileptic drugs might be helpful to prevent decreases in BMD.

Development of Multiplex PCR Detection of Blood-borne Viruses by Nucleic Acid Hybridization

Polymerase chain reaction (PCR) has been used as a substitute for conventional serological methods in order to provide blood or blood products free from contaminating viruses and recently attempts have focused to detect 2 or 3 viruses by a single multiplex PCR (M-PCR) reaction. We were able to detect human immunodeficiency virus type 1 (HIV-1), hepatitis C virus (HCV), hepatitis B virus (HBV) and human cytomegalovirus (HCMV) simultaneously by a single M-PCR. However detection by gel electrophoresis of the products from M-PCR suffers from drawbacks such as low sensitivity and product sizes. Here we report enhanced detection systems of M-PCR based on nucleic acid hybridization with arrays built on membrane. Membrane array was manufactured by spotting appropriate probe DNAs on nylon membrane. Single or multiplex PCR was performed and the PCR products were labeled with DIG and allowed to hybridize with the membrane array. Results indicate that nonspecific hybridization was not observed for membrane DNA array. Additionally, membrane array method could detect small amount of viruses that were not detectable by conventional gel electrophoresis. At least 25-fold, and in some cases more than 125-fold increases in sensitivity was obtained with DNA array method. Thus, the nucleic acid hybridization with membrane array could be applied for the detection of M-PCR of viruses in blood or blood products.

Effects of Antiepileptic Drugs on Thyroid Hormones and Lipid Profiles / 대한간질학회지

PURPOSE: It is known that serum thyroid hormones and lipid profiles are affected by the different biotransformation pathways of antiepileptic drugs (AEDs). The aim of this study was to evaluate thyroid functions and lipids in epileptic patients taking AEDs. METHODS: We prospectively examined serum thyroid hormone concentrations and lipid profiles in 45 patients with epilepsy and compared them with 45 healthy age- and sex-matched controls. We measured serum free T4 (FT4), thyroid stimulating hormone (TSH), thyroid peroxidase antibody (TPO-ab), thyroid globulin antibody (TG-ab), total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL) and triglycerides (TG). To analyze, the patient groups were divided into two groups:36 patients using hepatic enzyme inducing AEDs and 9 patients using non-enzyme-inducing AEDs. RESULTS: Mean age, sex and body mass index (BMI) were not different in both groups. The serum free T4 level of all patients was lower than that of the control group (p<0.05). The serum free T4 level of the patients taking hepatic enzyme inducing AEDs was lower than that of the control group. TSH, TPO-ab and TG-ab levels were not different in both groups. There was no correlation between free T4 levels and the duration of therapy in the patient group. For lipids, LDL, HDL, TG and total cholesterol, levels were not different in both groups. CONCLUSIONS: Hepatic enzyme inducing AEDs led to a decrease in free T4 levels but the TSH level remained normal. These findings seem to be not only due to liver enzyme induction but also hypothalamic interference of regulation of thyroid hormone production by the drugs. Lipid profiles were not significantly influenced by AEDs but further evaluation should be needed.

Ictal Vomiting Associated with Temporal Lobe Epilepsy of Dominant Hemisphere

Ictal vomiting is a rare clinical manifestation of temporal lobe epilepsy. This manifestation is considered a clinical lateralizing sign pointing toward seizure activity within the nondominant temporal lobe. However, we have experienced a case of ictal vomiting associated with temporal lobe epilepsy within the dominant hemisphere. The ictal vomiting occurred early in the course of the seizure when rhythmic discharges predominantly involved the left temporal lobe. This patient underwent a left anterior temporal lobectomy and experienced markedly reduced seizure frequency for more than 2 years.