BACKGROUND: Hypobetalipoproteinemia (HBL) is characterized by plasma concentration of lowdensity lipoprotein cholesterol below the fifth percentile in a healthy population. It has been suggested that HBL may be associated with apolipoprotein E (apoE) and apoB polymorphisms, such as apoB 8344 and apoB EcoRI. METHODS: Patients with HBL (n=51) and age-and- sex-matched healthy controls (n=136) were compared for apoE genotyping, apoB 8344 polymorphism and apoB EcoRI polymorphism. ApoE genotyping and apoB EcoRI polymorphism were determined by polymerase chain reaction (PCR) restriction fragment-length polymorphism. ApoB 8344 polymorphism was determined by the PCR-amplification refractory mutation system. We also Search truncated apoB with ECL western blotting in 23 HBL subjects. RESULTS: We could not find any truncated form of apoB. We found significant elevation of the apoE epsilon2 allele frequency of 0.147 in HBL cases compared with 0.063 in healthy controls (P=0.018). The ApoB 8344 polymorphism showed no significant difference between the HBL and the normal control groups. There were no significant apoB EcoRI allele frequency differences between the HBL and the normal groups. There were no significant apoB EcoRI allele frequency differences between the HBL and the normal groups. CONCLUSIONS: We could not find any relationship between HBL either with apoB 8344 or apoB EcoRI polymorphisms, but apoE epsilon2 allele seemed to be associated with HBL in Koreans.
Alleles ; Apolipoprotein E2 ; Apolipoproteins B ; Apolipoproteins E ; Apolipoproteins* ; Blotting, Western ; Cholesterol ; Gene Frequency ; Humans ; Hypobetalipoproteinemias ; Lipoproteins ; Plasma ; Polymerase Chain Reaction

No abstract available.
Bone Marrow* ; Necrosis*

BACKGROUND: Early diagnosis and treatment of acute coronary syndrome(ACS) encompassing acute myocardial infarction(AMI) and unstable angina(UA) is very important. Cardiac troponin T(cTnT) is known to be more specific to myocardium, and the level increases early and persistently during the period of 7 to 14 days after the onset of symptoms. The aim of this study was to evaluate the usefulness of cTnT for the diagnosis of ACS comparing with other biochemical markers. METHODS: The precision, linearity, lower limit of detection and interferences for cTnT by electrochemiluminescence were evaluated. cTnT and other conventional cardiac markers were determined for 128 AMI, 96 UA and 72 stable angina(SA) patients. The medical records of these patients were reviewed. RESULTS: cTnT-positive rates in AMI patients were 87.5-100% in all periods. cTnT positive rate was maintained as 100% from 3 hours to 96 hours after heart attack. Although CK-MB positive rate was as high as 85.7% at 6 hours, it decreased after 61 hours. The positive rate of LD and LD isoenzyme were very low(33.8-75%). In UA patients, mean positive rates of cTnT and CK-MB were 22.6% and 22.9% respectively. For the diagnosis of ACS comparing with SA, the sensitivity and specificity of cTnT were 63% and 94%(cut-off, 0.1 microgram/ml), meanwhile these of CK-MB were 53% and 90%, respectively(cut-off, 5 microgram/ml). CONCLUSIONS: cTnT was more useful and sensitive than CK-MB, LD, or LD isoenzyme. ACS also could be diagnosed with cTnT and CK-MB with sufficiently high specificity. cTnT seemed to be slightly more specific than CK-MB for the diagnosis of ACS.
Acute Coronary Syndrome* ; Angina, Unstable ; Biomarkers ; Diagnosis ; Early Diagnosis ; Heart ; Humans ; Limit of Detection ; Medical Records ; Myocardial Infarction ; Myocardium ; Sensitivity and Specificity ; Troponin T* ; Troponin*

Valproic acid (VPA) is a commonly prescribed anticonvulsant drug for the treatment of various forms of epilepsy. Concomitant administration of VPA and carbapenem antibiotics such as panipenem/ betamipron and meropenem has been reported to decrease the serum level of VPA. We observed seven cases which showed a decrease in serum levels of VPA due to concomitant use of VPA and carbapenem from January 2002 to October 2006 in a 750-bed university hospital, the average decrease of 70.4% was observed. Carbapenem antibiotics administrated concomitantly with VPA were panipenem (1 case), meropenem (3 cases), and imipenem (2 cases), and in one other case imipenem and meropenem were used sequentially. We found the VPA serum levels were significantly decreased with meropenem (n=4) more than with other carbapenem antibiotics (n=4, 89.3% vs. 51.5% decrease, P=0.03). Clinicians should be aware of this potential interaction, pay attention to the failure of seizure control due to decreased serum VPA levels with concomitant use of carbapenem antibiotics, and monitor VPA serum levels for those cases.
Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/administration & dosage/*therapeutic use ; Anticonvulsants/administration & dosage/*blood/therapeutic use ; Carbapenems/administration & dosage/*therapeutic use ; Drug Interactions ; Drug Therapy, Combination ; Epilepsy/*drug therapy ; Female ; Humans ; Imipenem/therapeutic use ; Male ; Middle Aged ; Thienamycins/therapeutic use ; Valproic Acid/administration & dosage/*blood/therapeutic use

BACKGROUND: Maternal serum prenatal quadruple screening includes testing for alpha-fetoprotein (AFP), human chorionic gonadotrophin (hCG), unconjugated estriol (uE3), and dimeric inhibin A (DIA). We evaluated quadruple screening using an automated platform and looked for any ethnic differences in the median values of each marker. METHODS: We measured the concentrations of each quadruple test analyte using the UniCel DxI 800 system (Beckman Coulter, USA) in 788 Korean mid-trimester maternal serum samples and calculated their median values using Benetech software (Benetech, Canada). We also compared the results with those obtained using the Immulite 2000 assay (Siemens Healthcare Diagnostics, USA) or ELISA (DSL, USA) in 442 samples. RESULTS: We obtained mid-trimester median values for each marker. The following are the comparative results for each test using the Immulite 2000 assay or ELISA (x) and the UniCel DxI 800 immunoassay (y): AFP, y=1.10x+0.01, r=0.925; uE3, y=0.28x+0.24, r=0.885; hCG, y=1.22x-3047.8, r=0.944; and DIA, y=0.86x+15.31, r=0.833. Assay results for each of the four markers showed good correlations. However, significant biases necessitated new median calculations of prenatal risk estimates in all four tests. CONCLUSIONS: We established gestational age-specific second-trimester median values for four markers in Korean samples using the UniCel DxI 800 immunoassay system. Despite significant bias, there were good correlations between the results obtained using the UniCel DxI 800 immunoassay and those obtained using the Immulite 2000 assay.
Biological Markers/blood ; Chorionic Gonadotropin/blood ; Enzyme-Linked Immunosorbent Assay ; Estriol/blood ; Female ; Gestational Age ; Humans ; Immunoassay/instrumentation/*methods ; Inhibins/blood ; Pregnancy ; Pregnancy Trimester, Second ; *Prenatal Diagnosis ; Reference Values ; Republic of Korea ; alpha-Fetoproteins/analysis

To evaluate avian hepatitis E virus (aHEV) as an RNA vaccine platform, open reading frame 2 (ORF2) of aHEV was replaced by heterologous genes, such as enhanced green fluorescent protein (eGFP) and hemagglutinin (HA)-tag, in aHEV infectious cDNA clones. eGFP and HA-tag replicons were expressed in leghorn male hepatoma (LMH) cells. To confirm expression of the heterologous protein, ORF2 was replaced with the antigenic S1 gene of infectious bronchitis virus (IBV). The IBVS1 replicon was expressed in LMH cells. To our knowledge, this is the first investigation showing potential as a RNA vaccine platform using an aHEV. In the future, it may be used in the development of RNA vaccines against various pathogens.

To evaluate avian hepatitis E virus (aHEV) as an RNA vaccine platform, open reading frame 2 (ORF2) of aHEV was replaced by heterologous genes, such as enhanced green fluorescent protein (eGFP) and hemagglutinin (HA)-tag, in aHEV infectious cDNA clones. eGFP and HA-tag replicons were expressed in leghorn male hepatoma (LMH) cells. To confirm expression of the heterologous protein, ORF2 was replaced with the antigenic S1 gene of infectious bronchitis virus (IBV). The IBVS1 replicon was expressed in LMH cells. To our knowledge, this is the first investigation showing potential as a RNA vaccine platform using an aHEV. In the future, it may be used in the development of RNA vaccines against various pathogens.

The aim of this study was to determine the effect of partial liquid ventilation (PLV) using a perfluorocarbon (PFC) on gas exchange and lung inflammatory response in a canine acute lung injury model. After inducing severe lung injury by oleic acid infusion, beagle dogs were randomized to receive either gas ventilation only (control group, n = 6) or PLV (PLV group, n = 7) by sequential instillation of 10 mL/kg of perfluorodecalin (PFC) at 30 min intervals till functional residual capacity was attained. Measurements were made every 30 min till 210 min. Then the lungs were removed and bronchoalveolar lavage (BAL) (35 mL/kg) was performed on the right lung and the left lung was submitted for histologic analysis. There was significant improvement in PaO2 and PaCO2 in the PLV group compared to the control group (p < 0.05) which was associated with a significant decrease in shunt (p < 0.05). There was no significant difference in parameters of lung mechanics and hemodynamics. There was a significant decrease in cell count and neutrophil percentage in BAL fluid and significantly less inflammation and exudate scores in histology in the PLV group (p < 0.05). We conclude that PLV with perfluorodecalin improves gas exchange and decreases inflammatory response in the acutely-injured lung.
Animal ; Blood Cell Count ; Bronchoalveolar Lavage Fluid ; Carbon Dioxide/analysis ; Disease Models, Animal ; Dogs ; Female ; Fluorocarbons/pharmacology* ; Hemodynamics ; Histocytochemistry ; Inflammation/prevention & control ; Lung Diseases/physiopathology* ; Lung Diseases/chemically induced ; Male ; Oleic Acid ; Oxygen/analysis ; Pulmonary Gas Exchange/drug effects* ; Pulmonary Ventilation/physiology* ; Respiratory Function Tests ; Ventilators, Mechanical

Sequestosome 1 (SQSTM1, p62), a ubiquitin binding protein, plays a role in cell signaling, oxidative stress, and autophagy. However, its functional role in inflammatory signaling is controversial. Recent studies have shown that p62 is negatively implicated in inflammatory responses. But, the precise molecular mechanisms by which p62 regulates inflammatory responses remain unclear. In this study, we report on a new regulatory role for p62 in TLR4-mediated signaling. p62 overexpression led to the suppression of NF-κB activation and the production of pro-inflammatory cytokines, TNF-α, IL-6, and IL-1β in response to TLR4 stimulation. In contrast, p62(−/−) mouse embryonic fibroblast (MEF) cells exhibited marked enhancement of NF-κB activation and production of pro-inflammatory cytokines by TLR4 stimulation, compared to p62(+/+) MEF cells. Additionally, the TLR4-induced activation of signal transduction was significantly augmented in p62(−/−) MEF cells, indicating that p62 was negatively implicated in TLR4-mediated signaling. Biochemical studies revealed that p62 interacted with the internal domain of evolutionarily conserved signaling intermediate in Toll pathways (ECSIT), which is critical for associating with the TNF receptor associated factor 6 (TRAF6)-ECSIT complex to activate NF-κB in TLR4 signaling. Interestingly, p62-ECSIT interaction inhibited the interaction between TRAF6 and ECSIT and attenuated the ubiquitination of ECSIT. Furthermore, upon LPS challenge, the mortality of p62(−/−) (p62-knockout) mice was markedly enhanced compared to p62(+/+) (p62 wild-type) mice. Taken together, our data demonstrate that p62 negatively regulated TLR4 signaling via functional regulation of the TRAF6-ECSIT complex.
Animals ; Autophagy ; Carrier Proteins ; Cytokines ; Fibroblasts ; Interleukin-6 ; Mice ; Mortality ; Oxidative Stress ; Signal Transduction ; TNF Receptor-Associated Factor 6 ; Toll-Like Receptor 4 ; Ubiquitin ; Ubiquitination

Two trials of external quality assessment for Therapeutic Drug Monitoring (TDM) subcommittee of Korean Association of Quality Assurance for Clinical Pathology (KAQACP) were performed in 2003. Number of participating laboratories were 80 which is similar to those of the previous year. Response rates were elevated to 100.0% for both trials. Two kinds of control materials were requested to be tested in each trial so that each institution could know the possible systematic error. In both trials, 20 test items were responded at least from one laboratory. The average drug item was 7.0 per institution, which was elevated slightly from 6.5 in recent 5 years. The most common test items were valproic acid, digoxin, phenytoin, carbamazepine, theophylline, and phenobarbital, which were peformed in more than 75% of participating laboratories, followed by cyclosporine, lithium, methotrexate, tacrolimus, vancomycin, amikacin, gentamycin, salicylate, tobramycin, acetaminophen, primidone, free phenytoin, and amitryptyline. The most widely used TDM analyzer was Abbott TDx/TDxFLx (52%), but its proportion were decreased slightly comparing with the previous years. The interlaboratory coefficients of variations were not greatly improved comparing with previous years. In conclusion, the TDM external quality assessment of 2003 showed grossly similar pattern comparing with those of previous year, except that the response rate was elevated to 100% and two levels of control material were used in each trials.
Acetaminophen ; Amikacin ; Carbamazepine ; Cyclosporine ; Digoxin ; Drug Monitoring* ; Gentamicins ; Korea* ; Lithium ; Methotrexate ; Pathology, Clinical ; Phenobarbital ; Phenytoin ; Primidone ; Tacrolimus ; Theophylline ; Tobramycin ; Valproic Acid ; Vancomycin