Predictive Value of Antiviral Effects in the Development of Hepatocellular Carcinoma in the General Korean Population with Chronic Hepatitis B

BACKGROUND/AIMS: The benefit of oral antiviral therapy in preventing hepatocellular carcinoma (HCC) in the general population is not well understood. We used a novel prediction method to estimate the risk of HCC in the Korean population based on various treatment guidelines. METHODS: The 5-year risk of HCC following antiviral therapy was calculated using an HCC risk prediction model. A virtual cohort that represented Koreans (>40 years old) with chronic hepatitis B virus (HBV) infection was established using the fifth National Health and Nutrition Examination Survey. The antiviral indications tested were the Korean National Health Insurance (NHI) and European Association for the Study of the Liver (EASL) guidelines as well as a new extended indication (serum HBV DNA >2,000 IU/mL regardless of serum aminotransferase level). RESULTS: A total of 993,872 subjects were infected with HBV in the general Korean population. Over a 5-year period, 2,725 HCC cases were predicted per 100,000 persons (0.55%/yr). When the cohort was treated based on the Korean NHI, the EASL, and the newly extended indications, HCC risks decreased to 2,531 (−7.1%), 2,089 (−23.3%), and 1,122 (−58.8%) cases per 100,000 persons, respectively (p<0.0001). CONCLUSIONS: Simulated risk prediction suggests that extending of oral antiviral indication may reduce the HCC risk in the general population.

Massive Upper Gastrointestinal Bleeding from Multiple Gastrointestinal Stromal Tumor in a Neurofibromatosis Patient / 대한소화기학회지

No abstract available.

Helicobacter pylori Infection Enhances Gastric Mucosal Inflammation in Individuals Carrying the 260-T Allele of the CD14 Gene

BACKGROUND/AIMS: We aim to evaluate the association between promoter polymorphism of the clusters of differentiation 14 (CD14) gene and Helicobacter pylori-induced gastric mucosal inflammation in a healthy Korean population. METHODS: The study population consisted of 267 healthy subjects who visited our hospital for free nationwide gastric cancer screening. Promoter polymorphism at -260 C/T of the CD14 gene was determined by polymerase chain reaction and restriction fragment length polymorphism analysis. The severity of gastric mucosal inflammation was estimated by a gastritis score based on the sum of the values of the grade and activity of the gastritis. Expression of soluble CD14 (sCD14) was assessed by quantitative sandwich ELISA. RESULTS: CD14 polymorphism was not associated with H. pylori infection. There were no significant differences in gastritis scores among the genotype subgroups, but subjects carrying the CD14 -260 CT/TT genotype had significantly higher sCD14 levels than those carrying the CC genotype. Subjects with the 260-T allele of the CD14 gene and H. pylori infection had significantly higher sCD14 levels than those with the same genotype but without infection. CONCLUSIONS: In individuals with the T allele at the -260 site of the promoter region of the CD14 gene, H. pylori infection accentuates gastric mucosal inflammation.

Pulmonary Hypertension Associated with Acute Hypoxic Pulmonary Vasoconstriction in a Patient with Acute Myeloid Leukemia / 대한내과학회지

Hypoxic pulmonary vasoconstriction is a unique response of the pulmonary circulation to hypoxia. It constitutes part of the self-regulatory mechanism by which pulmonary capillary blood flow is adjusted to alveolar ventilation for maintaining the optimal balance of ventilation and perfusion. In pathological conditions, hypoxic pulmonary vasoconstriction may occur as an acute episode or as a sustained response with pulmonary hypertension and vascular remodeling. We report a case of reversible pulmonary hypertension induced by acute hypoxic pulmonary vasoconstriction in an 18-year-old man with relapsed acute myeloid leukemia, complicated with severe anemia and pneumonia.

A Case of Visual and Auditory Hallucinations during Intravenous Voriconazole Therapy / 감염과화학요법

Voriconazole is a triazole with broad spectrum antifungal activity, and it is currently considered to be the first-line agent for the treatment of invasive aspergillosis. We report here on a case of visual and auditory hallucinations during intravenous treatment with voriconazole in association with a high trough level. A 28-year-old man with acute myelogenous leukemia was admitted for re-induction remission chemotherapy. During the persistent neutropenic fever, intravenous voriconazole was administered for the suspected invasive fungal pneumonia. He began to have visual hallucinations on the 1st day and auditory hallucinations on the 3rd day of voriconazole therapy. The plasma peak and trough concentration levels of voriconazole were 9.9 and 7.4 microg/ml, respectively, on the 3rd day. The hallucinations resolved after changing to amphotericin B deoxycholate, and the plasma concentration of voriconazole dropped to less than 0.5 microg/ml. The genotype of the CYP2C19 alleles was classified as a heterozygous extensive metabolizer. We suggest that therapeutic drug monitoring of voriconazole is indicated for a case that is suspicious for a voriconazole-related adverse event.

A Case of Bleeding on the Ampulla of Vater Due to Angiodysplasia in a Patient with End Stage Renal Disease / 대한소화기내시경학회지

Gastrointestinal angiodysplasia is one of the causes of acute and chronic gastrointestinal bleeding, and gastrointestinal angiodysplasia makes up 2~6% of all the cases of upper gastrointestinal bleeding. Bleeding from the ampulla of Vater is very rare. We report here on an unusual case of bleeding from angiodysplasia at the ampulla of Vater in a 58-aged woman with end stage renal failure. This lesion was successfully treated with endoscopic argon plasma coagulation.

Identification of molecular markers for the oncogenic differentiation of hepatocellular carcinoma

The aim of this study was to identify molecular markers associated with oncogenic differentiation in hepatocellular carcinoma (HCC). Using an unsupervised clustering method with a cDNA microarray, HCC (T) gene expression profiles and corresponding non-tumor tissues (NT) from 40 patients were analyzed. Of total 217 genes, 72 were expressed preferentially in HCC tissues. Among 186 differentially regulated genes, there were molecular chaperone and tumor suppressor gene clusters in the Edmondson grades I and II (GI/II) subclass compared with the liver cirrhosis (LC) subclass. The Edmondson grades III and IV (GIII/IV) subclass with a poor survival (P = 0.0133) contained 122 differentially regulated genes with a cluster containing various metastasis- and invasion-related genes compared with the GI/II subclass. Immunohistochemical analysis revealed that ANXA2, one of the 72 genes preferentially expressed in HCC, was over-expressed in the sinusoidal endothelium and in malignant hepatocytes in HCC. The genes identified in the HCC subclasses will be useful molecular markers for the genesis and progression of HCC. In addition, ANXA2 might be a novel marker for tumor angiogenesis in HCC.

FCAnalyzer: A Functional Clustering Analysis Tool for Predicted Transcription Regulatory Elements and Gene Ontology Terms

Numerous studies have reported that genes with similar expression patterns are co-regulated. From gene expression data, we have assumed that genes having similar expression pattern would share similar transcription factor binding sites (TFBSs). These function as the binding regions for transcription factors (TFs) and thereby regulate gene expression. In this context, various analysis tools have been developed. However, they have shortcomings in the combined analysis of expression patterns and significant TFBSs and in the functional analysis of target genes of significantly overrepresented putative regulators. In this study, we present a web-based A Functional Clustering Analysis Tool for Predicted Transcription Regulatory Elements and Gene Ontology Terms (FCAnalyzer). This system integrates microarray clustering data with similar expression patterns, and TFBS data in each cluster. FCAnalyzer is designed to perform two independent clustering procedures. The first process clusters gene expression profiles using the K-means clustering method, and the second process clusters predicted TFBSs in the upstream region of previously clustered genes using the hierarchical biclustering method for simultaneous grouping of genes and samples. This system offers retrieved information for predicted TFBSs in each cluster using Match(TM) in the TRANSFAC database. We used gene ontology term analysis for functional annotation of genes in the same cluster. We also provide the user with a combinatorial TFBS analysis of TFBS pairs. The enrichment of TFBS analysis and GO term analysis is statistically by the calculation of P values based on Fisher's exact test, hypergeometric distribution and Bonferroni correction. FCAnalyzer is a web-based, user-friendly functional clustering analysis system that facilitates the transcriptional regulatory analysis of co-expressed genes. This system presents the analyses of clustered genes, significant TFBSs, significantly enriched TFBS combinations, their target genes and TFBS-TF pairs.

Comparative Statistic Module (CSM) for Significant Gene Selection

Comparative Statistic Module(CSM) provides more reliable list of significant genes to genomics researchers by offering the commonly selected genes and a method of choice by calculating the rank of each statistical test based on the average ranking of common genes across the five statistical methods, i.e. t-test, Kruskal-Wallis (Wilcoxon signed rank) test, SAM, two sample multiple test, and Empirical Bayesian test. This statistical analysis module is implemented in Perl, and R languages.

Expression of p53, p16, PTEN, and c-myc Gene with Cisplatin Treatment in Cisplatin Resistant Ovarian Cancer Cell Line / 대한산부인과학회잡지

OBJECTIVE: The chemotherapeutic agent Cisplatin (cis-diammminedichloroplatinum (II)) is particularly effective against ovarian carcinoma, however, its clinical success is limited by recurrent drug resistant tumors. It is mandatory to reveal the mechanism of cisplatin resistance for the ovarian cancer treatment or prognosis. This study assessed the expression of p53, p16, PTEN, and c-myc genes with cisplatin treatment in human ovarian cancer cell lines; cisplatin-sensitive (A2780) and cisplatin-resistant (A2780/CP70) ovarian cancer cell line to elucidate the mechanism of cisplatin resistance. METHODS: Cytotoxic assay for cisplatin was performed in cisplatin-sensitive ovarian cancer cell line, A2780 and cisplatin-resistant ovarian cancer cell line, A2780/CP70. After cisplatin treatment, expression of p53, p16, PTEN, c-myc was analyzed by Western blot analysis. RESULTS: PTEN expression was significantly about 30% higher in A2780 than in A2780/CP70. p16 expression was defective in both cell lines. p53 and c-myc expression was no difference in cancer cell lines. After cisplatin treatment, the expression of p53, PTEN, c-myc genes increased 2-3 times in both cell lines. CONCLUSION: Relatively lower expression of PTEN was detected in A2780/CP70 suggesting that PTEN expression might play a role in the development of cisplatin resistance in ovarian cancer cell line, A2780/ CP70.

RHD Genotyping in RhD-negative Korean Donors by Polymerase Chain Reaction: Sequence Specific Primers(PCR-SSP) Method / 대한임상병리학회지

BACKGROUND: In Caucacians, almost all RhD-negatives have deletion in RHD gene and the RHD genotyping by PCR-SSP is a valuable tool. The aim of this study is to investigate the frequency of RHD gene deletion in RhD-negative Korean donors and evaluate the clinical usefulness of various RHD genotyping methods in Korean. METHODS: Two hundred fifty RhD-positive blood obtained from Blood Transfusion Research Institute and 119 RhD-negative blood samples were obtained from Korea Red Cross Dong Bu Center. Phenotyping of RhD, RhC/c, and RhE/e antigen was performed using polyclonal and monoclonal antibodies(Dade AG, Switzerland). PCR-SSP was performed by primer sets, specific for exon 3, exon 4, exon 5, exon 6, exon 7, exon 9, and exon 10 of RHD gene and for exon 2, intron 4, and intron 4-exon 5 common to RHD and RHCE genes. RESULTS: The phenotypes of 250 RhD-positives consisted of 106(42.4%) CCee, 93(37.2%) CcEe, 26(10.4%) ccEE, 21(8.4%) Ccee, 3(1.2%) ccEe, and 1(0.4%) ccee. In RhD-negative donors, 62(52.1%) were ccee, 37(31.1%) Ccee, 10(8.4%) ccEE, 6(5.0%) CcEe, 2(1.7%) ccEE, and 2(1.7%) CCee. Twenty-two out of 101 RhD-negatives showed no deletion in all used methods. Deletion frequency of RhD negatives varied according to the methods: 76(75.3%) in intron 4-exon 5 boundary; 74(73.3%) in intron 4; 72(71.3%) in exon 4; 67(66.3%) in exon 7; 63(62.4%) in exon 10; 9(8.9%) in exon 5; no deletion in exon 3, exon 6, and exon 9. Different RhD phenotypes also showed different RHD gene deletion frequency: 80-90% deletion in ccee; 70% in ccEe; 40-50% in Ccee and CcEe; no deletion in CCee phenotypes. CONCLUSIONS: RHD gene deletion frequency varied according to the methods applied and individual's own RhD phenotypes. Therefore, RHD genotyping is not appropriate for a routine test in Blood Bank and individual variation should be considered in prenatal care of RhD-negative women.

Identification of Fetal Gender Using Maternal Plasma DNA / 대한산부인과학회잡지

OBJECTIVE: To identify fetal gender using fetal DNA in maternal plasma. METHODS: DNA from maternal plasma of 55 pregnant women(47: inpatients, 8: outpatients) underwent a sensitive Y-PCR assay to identify gender. RESULTS: Of the inpatients, fetus-derived Y sequences were detected in 26(80.6%) of the 31 maternal plasma samples from women bearing male fetuses. None of the 16 women bearing female fetuses had positive results from plasma DNA. Eighteen weeks is earliest gestation of gender identification. Of the outpatients(GA 8-11 weeks), fetus-derived Y sequences were detected in 7 of the 8 maternal plasma. Only one patient's fetal gender(GA 9 weeks) was identified. The others were not identified at this moment. CONCLUSION: We identified fetal DNA in maternal plasma. The sensitivity of Y-PCR was 80.6% in women bearing male fetus and the specificity was 100% in women bearing female fetus.

Infantile and Childhood Shigellosis in Dae Jon area

Clinical and bacteriological studies were made on 37 cases of infantile and childhood shigellosis treated at pediatric department of St. Mary's hospital in Dae Jon from Jan. 1978 to Dec. 1978. The following results were obtained. 1. In sex distribution 21 were male and rest of them were female, and the M/F ratio was 1.8:1.0. 2. The peak age incidence showed the children of 1 to 6 years old. 3. The most frequent symptom was fever(76%) and abdominal pain was next. 4. S. flexneri was most frequentkly isolated (62.2%) and the next was S. sonnei(35.1%). 5. The result of sensitivity test in this study revealed that tobramycin was most commonly effective (92%) and cephaloridin was next. Ampicillin was less sensitive (22%) than the previous reports.