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1.  The relationship of histologic activity to serum ALT, HCV genotype and HCV RNA titers in chronic hepatitis C. 
Journal of Korean Medical Science  2001;16(5):585-591.
It is unclear whether serum ALT levels or virological characteristics of hepatitis C virus(HCV) including HCV genotypes and HCV RNA titers, can reflect the degree of histological injury in chronic hepatitis C. The aim of this study was to investigate the relationships between the levels of histological damage and serum ALT levels, HCV genotypes or circulating HCV RNA titers in chronic hepatitis C. A total of 56 patients underwent liver biopsy and the histological activity index (HAI) was evaluated by Knodell's scoring system. HCV genotype by RT-nested PCR and HCV RNA quantitation by competitive RT-PCR were performed. Thirty-four patients were infected with HCV genotype 1b, 20 patients with genotype 2a, and 2 patients with undetermined type. Serum ALT levels were not positively correlated with total HAI score or HCV RNA titers, but showed a linear correlation with scores of piecemeal necrosis (r=0.32, p<0.05) and portal inflammation (r=0.27, p<0.05). HCV genotype had no significant correlation with RNA titers, HAI score or with serum ALT levels. Also, no statistical relationship was seen between HCV RNA titer and HAI score. These results suggest that liver histology is essential to evaluate the severity of chronic hepatitis C precisely.
PMCID: PMC3057604  PMID: 11641527
2.  Two cases of common bile duct stone after liver transplantation. 
Biliary complications after orthotopic liver transplants are a continuing cause of morbidity and mortality. Biliary stones and sludge are less well known complications of hepatic transplantation, although they have long been recognized. Recently we experienced two cases of biliary stones developed after liver transplantation. One 32-year-old male, who frequently admitted due to recurrent cholangitis, was treated with percutaneous transhepatic biliary drainage and choledochojejunostomy with cholecystectomy. The other 58-year-old male, who had stones in commone bile duct, was treated by endoscopic manipulation. They are in good condition without recurrent bile duct stones or its accompanying complications. Although stones and sludge are relatively infrequent after liver transplantation, surgical or interventional radiologic treatments are usually performed for treatment.
PMCID: PMC3054171  PMID: 10102533
3.  Ventricular tachycardia and exercise related syncope in children with structurally normal hearts: emphasis on repolarisation abnormality. 
British Heart Journal  1995;73(6):544-547.
OBJECTIVE--To emphasize the importance of ventricular tachycardia associated with repolarisation abnormality in syncope associated with exercise. DESIGN--Retrospective analysis of data on children presenting with syncope between 1985 and 1993. PATIENTS--5 apparently normal children with recurrent exercise related syncope associated with electrocardiographically abnormal TU complexes. RESULTS--3 children were diagnosed as having an intermediate form of the long QT syndrome and catecholamine sensitive ventricular tachycardia because the abnormal TU complexes were associated with polymorphic ventricular tachycardia that was not typical of torsades de pointes. Tachycardia was induced by exercise in all patients and by isoprenaline in the one patient who was tested. One patient also had sinus node dysfunction. One child had incessant salvos of polymorphic ventricular arrhythmias and intermittent abnormal TU complexes suggestive of repolarisation abnormalities. The other had typical congenital long QT syndrome. Treatment was effective in three patients; two patients took a beta blocker alone and one took a beta blocker and low doses of amiodarone. One patient died suddenly, death being associated with sinus node dysfunction. In one patient with incessant ventricular arrhythmias treatment with a beta blocker, amiodarone, or Ic drugs was ineffective and always associated with proarrhythmia or syncope. He was not given further treatment and was asymptomatic despite having mild cardiomegaly. CONCLUSIONS--Ventricular tachycardia associated with repolarisation abnormality was an important cause of exercise related syncope in apparently normal children. TU complex abnormalities can be identified by repeated electrocardiography. beta Blockers are effective in preventing recurrent episodes. The role of amiodarone in this type of ventricular tachycardia needs further evaluation.
PMCID: PMC483917  PMID: 7626354
4.  FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium 
Agarwal, D | Pineda, S | Michailidou, K | Herranz, J | Pita, G | Moreno, L T | Alonso, M R | Dennis, J | Wang, Q | Bolla, M K | Meyer, K B | Menéndez-Rodríguez, P | Hardisson, D | Mendiola, M | González-Neira, A | Lindblom, A | Margolin, S | Swerdlow, A | Ashworth, A | Orr, N | Jones, M | Matsuo, K | Ito, H | Iwata, H | Kondo, N | Hartman, M | Hui, M | Lim, W Y | T-C Iau, P | Sawyer, E | Tomlinson, I | Kerin, M | Miller, N | Kang, D | Choi, J-Y | Park, S K | Noh, D-Y | Hopper, J L | Schmidt, D F | Makalic, E | Southey, M C | Teo, S H | Yip, C H | Sivanandan, K | Tay, W-T | Brauch, H | Brüning, T | Hamann, U | Dunning, A M | Shah, M | Andrulis, I L | Knight, J A | Glendon, G | Tchatchou, S | Schmidt, M K | Broeks, A | Rosenberg, E H | van't Veer, L J | Fasching, P A | Renner, S P | Ekici, A B | Beckmann, M W | Shen, C-Y | Hsiung, C-N | Yu, J-C | Hou, M-F | Blot, W | Cai, Q | Wu, A H | Tseng, C-C | Van Den Berg, D | Stram, D O | Cox, A | Brock, I W | Reed, M W R | Muir, K | Lophatananon, A | Stewart-Brown, S | Siriwanarangsan, P | Zheng, W | Deming-Halverson, S | Shrubsole, M J | Long, J | Shu, X-O | Lu, W | Gao, Y-T | Zhang, B | Radice, P | Peterlongo, P | Manoukian, S | Mariette, F | Sangrajrang, S | McKay, J | Couch, F J | Toland, A E | Yannoukakos, D | Fletcher, O | Johnson, N | Silva, I dos Santos | Peto, J | Marme, F | Burwinkel, B | Guénel, P | Truong, T | Sanchez, M | Mulot, C | Bojesen, S E | Nordestgaard, B G | Flyer, H | Brenner, H | Dieffenbach, A K | Arndt, V | Stegmaier, C | Mannermaa, A | Kataja, V | Kosma, V-M | Hartikainen, J M | Lambrechts, D | Yesilyurt, B T | Floris, G | Leunen, K | Chang-Claude, J | Rudolph, A | Seibold, P | Flesch-Janys, D | Wang, X | Olson, J E | Vachon, C | Purrington, K | Giles, G G | Severi, G | Baglietto, L | Haiman, C A | Henderson, B E | Schumacher, F | Le Marchand, L | Simard, J | Dumont, M | Goldberg, M S | Labrèche, F | Winqvist, R | Pylkäs, K | Jukkola-Vuorinen, A | Grip, M | Devilee, P | Tollenaar, R A E M | Seynaeve, C | García-Closas, M | Chanock, S J | Lissowska, J | Figueroa, J D | Czene, K | Eriksson, M | Humphreys, K | Darabi, H | Hooning, M J | Kriege, M | Collée, J M | Tilanus-Linthorst, M | Li, J | Jakubowska, A | Lubinski, J | Jaworska-Bieniek, K | Durda, K | Nevanlinna, H | Muranen, T A | Aittomäki, K | Blomqvist, C | Bogdanova, N | Dörk, T | Hall, P | Chenevix-Trench, G | Easton, D F | Pharoah, P D P | Arias-Perez, J I | Zamora, P | Benítez, J | Milne, R L
British Journal of Cancer  2014;110(4):1088-1100.
Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium.
Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression.
Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95% confidence interval=1.02–1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2.
Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2.
PMCID: PMC3929867  PMID: 24548884
breast cancer; SNP; FGF receptors; susceptibility; disease subtypes
5.  Phase II study of pazopanib monotherapy in metastatic gastroenteropancreatic neuroendocrine tumours 
British Journal of Cancer  2013;109(6):1414-1419.
Treatment options for patients with metastatic gastroenteropancreatic neuroendocrine tumours (GEP NETs) are still limited. We investigated the antitumour activity and safety profile of pazopanib – a multitarget drug with anti-angiogenic activity in patients with metastatic GEP NETs.
This was a nonrandomised, open-labeled, single-center phase II study. Pazopanib was orally administered at a dose of 800 mg daily continuously with a 28-day cycle. The primary end point was an objective response rate according to Response Evaluation Criteria in Solid Tumors (RECIST). The secondary end points were progression-free survival (PFS), overall survival (OS) and safety. An independent review of objective response was planned. The trial is registered with, NCT number 01099540. Correlative biomarker analyses were performed.
Between April 2010 and February 2012, a total of 37 patients were enrolled. Thirty-two percent of the enrolled patients had pancreatic primary and 22% of the patients had colorectal primary NETs. This phase II study demonstrated an objective response rate of 18.9% (7 of the 37, 95% CI 8.0–35.2) and a disease control rate (CR+confirmed PR+stable disease) of 75.7% (28 of the 37, 95% CI, 58.8–88.2) in metastatic GEP NETs. The independent review demonstrated a higher overall response rate of 24.3% (95% CI, 11.8–41.2%) with nine confirmed PRs.
Pazopanib showed a comparable efficacy to other targeted agents not only in pancreatic NETs but also in NETs originating from gastrointestinal (GI) tract.
PMCID: PMC3776983  PMID: 23989950
neuroendocrine tumours; pazopanib; chemotherapy; chromogranin A; positron-emission tomography
6.  CYP2D6 Genotype and Adjuvant Tamoxifen: Meta-Analysis of Heterogeneous Study Populations 
The International Tamoxifen Pharmacogenomics Consortium was established to address the controversy regarding cytochrome P450 2D6 (CYP2D6) status and clinical outcomes in tamoxifen therapy. We performed a meta-analysis on data from 4,973 tamoxifen-treated patients (12 globally distributed sites). Using strict eligibility requirements (postmenopausal women with estrogen receptor–positive breast cancer, receiving 20 mg/day tamoxifen for 5 years, criterion 1); CYP2D6 poor metabolizer status was associated with poorer invasive disease–free survival (IDFS: hazard ratio = 1.25; 95% confidence interval = 1.06, 1.47; P = 0.009). However, CYP2D6 status was not statistically significant when tamoxifen duration, menopausal status, and annual follow-up were not specified (criterion 2, n = 2,443; P = 0.25) or when no exclusions were applied (criterion 3, n = 4,935; P = 0.38). Although CYP2D6 is a strong predictor of IDFS using strict inclusion criteria, because the results are not robust to inclusion criteria (these were not defined a priori), prospective studies are necessary to fully establish the value of CYP2D6 genotyping in tamoxifen therapy.
PMCID: PMC3904554  PMID: 24060820
7.  CT and MRI of fibrous dysplasia of the spine 
The British Journal of Radiology  2012;85(1015):996-1001.
The purpose of this study was to present the CT and MRI findings of patients with fibrous dysplasia (FD) of the spine.
Among the patients with pathologically proven skeletal FD, 12 (8 males and 4 females; mean age, 43 years) who were evaluated with either spine CT or MRI were included. The number and location of the involved vertebral segments, the presence of lytic lesions, ground-glass opacity (GGO), an expansile nature, cortical disruption, a sclerotic rim, a decrease in body height and contour deformity were examined on CT scans (n = 12), while signal intensity, enhancement patterns and the presence of a dark signal rim on the lesion were examined using MRI (n = 9).
Nine patients had polyostotic FD, including one with an isolated spinal localisation, while three had monostotic FD. An expansile nature (n = 3) and osteolytic lesions with GGO (n = 3) were seen. On CT images, GGO was noted in all patients. An expansile nature (n = 11) and presence of lytic lesions (n = 11) were noted. A decrease in body height (n = 9) and sclerotic rim formation (n = 9) were indicated. Contour deformities were visible in six patients. The MRI findings were non-specific. Dark signal rims were visible on MRI in seven patients.
Typical imaging findings of extraspinal FD were noted on spine CT scans. These characteristic CT imaging findings of spinal FD may be helpful in differentiating FD from other common spine diseases.
PMCID: PMC3474066  PMID: 22167510
8.  Value of diffusion-weighted imaging in the detection of viable tumour after neoadjuvant chemoradiation therapy in patients with locally advanced rectal cancer: comparison with T2 weighted and PET/CT imaging 
The British Journal of Radiology  2012;85(1013):577-586.
To evaluate the added value of diffusion-weighted imaging (DWI) in combination with T2 weighted imaging (T2WI) compared with T2WI alone or positron emission tomography (PET)/CT for detecting viable tumour after neoadjuvant chemoradiation therapy (CRT) in patients with locally advanced rectal cancer.
50 consecutive patients with locally advanced rectal cancer (≥T3 or lymph node positive) who underwent neoadjuvant CRT and subsequent surgery were enrolled in this retrospective study. All patients underwent 3.0 T rectal MRI and PET/CT after completing CRT. For qualitative analysis, two radiologists independently reviewed T2WI alone and DWI with T2WI over a 1-month interval. One nuclear medicine physician reviewed PET/CT images using a five-point scale. Diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for detecting viable tumour were assessed. For quantitative analysis, the apparent diffusion coefficients (ADCs) of the lesions were measured and compared between the viable tumour group and non-viable tumour groups.
For detecting viable tumours, DWI with T2WI improved diagnostic accuracies (Reviewer 1 detected 90%; Reviewer 2, 86%) over T2WI alone (Reviewer 1 detected 76%, p=0.5; Reviewer 2, 64%, p=0.013) or PET/CT (48%, p<0.001). The sensitivity of DWI with T2WI (Reviewer 1 detected 98%; Reviewer 2, 91%) was significantly higher than those of T2WI alone (Reviewer 1 detected 77%; Reviewer 2, 64%) or PET-CT (43%, p<0.05). Only for Reviewer 2 was the NPV of DWI with T2WI (43%) significantly different from that of PET/CT (17%, p<0.05). The specificities and PPVs of DWI with T2WI were not improved over those of T2WI alone or of PET/CT (both p>0.05). The mean ADC of the viable tumour group (0.93×10−3 mm2 sc−1) was significantly lower than that of the non-viable tumour group (1.55×10−3 mm2 sc−1, p<0.0001).
Adding DWI to T2WI is helpful for detecting viable tumours after neoadjuvant CRT compared with T2WI alone or PET/CT in patients with locally advanced rectal cancer.
PMCID: PMC3479876  PMID: 21343320
9.  MRI features of serous oligocystic adenoma of the pancreas: differentiation from mucinous cystic neoplasm of the pancreas 
The British Journal of Radiology  2012;85(1013):571-576.
The purpose of this study was to describe the MRI features of the benign pancreatic neoplasm serous oligocystic adenoma (SOA) that differ from those of mucinous cystic neoplasm (MCN), a neoplasm with the potential for malignant degeneration.
Seven patients with SOA (seven women; mean age 36.6 years) and eight patients with MCN (eight women: mean age 39.9 years) were included. Several imaging features were reviewed: mass size, location, shape, wall thickness, cyst configuration (Type I, unilocular; Type II, multiple clustered cyst; Type III, cyst with internal septation) and signal intensity of the lesion with heterogeneity.
SOA lesions were smaller (3.4 cm) than those of MCN (9.3 cm) (p=0.023). The commonest lesion shape was lobulated (85.7%) for SOA, but oval (50.0%) or lobulated (37.5%) for MCN (p=0.015). The most common cyst configuration was Type II (85.7%) for SOA and Type III (75.0%) for MCN (p=0.008). Heterogeneity of each locule in T1 weighted images was visible in all cases of MCN, but in no case for SOA (p=0.004).
SOA could be differentiated from MCN by identifying the imaging features of lobulated contour with multiple clustered cyst configurations and homogeneity of each locule in T1 weighted MR images.
PMCID: PMC3479889  PMID: 21304008
10.  Clinical significance of CD151 overexpression in subtypes of invasive breast cancer 
British Journal of Cancer  2012;106(5):923-930.
CD151 is a member of the tetraspanin family, which interacts with laminin-binding integrins and other tetraspanins. This protein is implicated in motility, invasion, and metastasis of cancer cells, but the prevalence of CD151 expression in subtypes of breast cancers and its influence on clinical outcome remains to be evaluated.
Methods and results:
The immunohistochemistry-based tissue microarray analysis showed that 127 (14.3%) cases overexpressed CD151 among 886 breast cancer patients. CD151 overexpression was found to be significantly associated with larger tumour size, higher nodal stage, advanced stage, absence of oestrogen receptor and progesterone receptor, and human epidermal growth factor receptor 2 overexpression. CD151 overexpression resulted in poorer overall survival (OS) (P<0.001) and disease-free survival (P=0.02), and stage II and III patients with CD151 overexpression demonstrated substantially poorer OS (P=0.0474 and 0.0169). In the five subtypes analyses, CD151 overexpression retained its adverse impact on OS in the Luminal A (P=0.0105) and quintuple-negative breast cancer (QNBC) subtypes, one subgroup of triple-negative breast cancer (P=0.0170). Multivariate analysis that included stage, subtype, and adjuvant chemotherapy showed that CD151 overexpression was independently associated with poor OS in invasive breast cancer.
CD151 overexpression may be a potential molecular therapeutic target for breast cancer, especially in QNBC subtype and more advanced stages of breast cancer.
PMCID: PMC3306846  PMID: 22294188
CD151; breast cancer; five subtypes; prognosis; tetraspanin
12.  Achromatic nested Kirkpatrick–Baez mirror optics for hard X-ray nanofocusing 
Journal of Synchrotron Radiation  2011;18(Pt 4):575-579.
A nested Kirkpatrick–Baez mirror pair has been designed, fabricated and tested for achromatic nanofocusing synchrotron hard X-rays. The prototype system achieved a FWHM focal spot of about 150 nm in both horizontal and vertical directions.
The first test of nanoscale-focusing Kirkpatrick–Baez (KB) mirrors in the nested (or Montel) configuration used at a hard X-ray synchrotron beamline is reported. The two mirrors are both 40 mm long and coated with Pt to produce a focal length of 60 mm at 3 mrad incident angle, and collect up to a 120 µm by 120 µm incident X-ray beam with maximum angular acceptance of 2 mrad and a broad bandwidth of energies up to 30 keV. In an initial test a focal spot of about 150 nm in both horizontal and vertical directions was achieved with either polychromatic or monochromatic beam. The nested mirror geometry, with two mirrors mounted side-by-side and perpendicular to each other, is significantly more compact and provides higher demagnification than the traditional sequential KB mirror arrangement. Ultimately, nested mirrors can focus larger divergence to improve the diffraction limit of achromatic optics. A major challenge with the fabrication of the required mirrors is the need for near-perfect mirror surfaces near the edge of at least one of the mirrors. Special polishing procedures and surface profile coating were used to preserve the mirror surface quality at the reflecting edge. Further developments aimed at achieving diffraction-limited focusing below 50 nm are underway.
PMCID: PMC3267635  PMID: 21685674
hard X-ray nanofocusing; achromatic; nested Kirkpatrick–Baez; Montel
13.  Percutaneous transluminal coronary angioplasty in a child with Kawasaki disease. 
Journal of Korean Medical Science  1998;13(6):693-695.
A successful attempt at percutaneous transluminanl coronary angioplasty (PTCA) to relieve stenosis of the mid-portion of the left anterior descending artery was achieved in a 6-year 9-month old boy who had multiple coronary aneurysms and stenosis due to Kawasaki disease. Despite the progression of coronary stenosis he had been well except for the perfusion defect of the anterior wall of myocardium on 99mTc-MIBI SPECT with dipyridamole infusion until PTCA was carried out after 4-year 4-months of the onset of illness. The area of stenosis was 70% before PTCA and 20% after PTCA. No restenosis at the site of PTCA was observed on follow-up angiography at 26 months after PTCA. This successful attempt may indicate that this procedure should be considered early in subclinical stenosis to prevent ischemic cardiac damage.
PMCID: PMC3054539  PMID: 9886184
14.  Molecular and functional expression of anion exchangers in cultured normal human nasal epithelial cells 
Anions have an important role in the regulation of airway surface liquid (ASL) volume, viscosity and pH. However, functional localization and regulation of anion exchangers (AEs) have not been clearly described. The aim of this study was to investigate the regulation of AE mRNA expression level in accordance with mucociliary differentiation and the functional expression of AEs cultured normal human nasal epithelial (NHNE) cells.
Nasal mucosal specimens from three patients are obtained and serially cultured cells are subjected to morphological examinations, RT-PCR, Western blot analysis and immunocytochemistry. AE activity is assessed by pHi measurements.
Expression of ciliated cells on the apical membrane and expression of MUC5AC, a marker of mucous differentiation, increased with time. AE2 and SLC26A4 mRNA expression decreased as mucociliary differentiation progressed, and AE4, SLC26A7 and SLC26A8 mRNA expression increased on the 14th and 28th day after confluence. Accordingly, AE4 protein expression also progressively increased. AE activity in 100 mm K+ buffer solutions was nearly twofold higher than that in 5 mm K+ buffer solutions. Moreover, only luminal AE activity increased about fourfold over the control in the presence of 5 μm forskolin. In the presence of 100 μm adenosine-5′-triphosphate (ATP) which evokes intracellular calcium signalling through activation of purinergic receptors, only luminal AE activity was again significantly increased. On the other hand, 500 μm 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS), an inhibitor of most SLC4 and SLC26AE isoforms, nearly abolished AE activity in both luminal and basolateral membranes. We found that AE activity was affected by intracellular cAMP and calcium signalling in the luminal membrane and was DIDS-sensitive in both membranes of cultured NHNE cells.
Our findings through molecular and functional studies using cultured NHNE cells suggest that AEs may have an important role in the regulation of ASL.
PMCID: PMC2040222  PMID: 17635413
anion exchangers; nasal epithelium; cell differentiation
15.  Anomalous subaortic position of the brachiocephalic vein (innominate vein): an echocardiographic study. 
British Heart Journal  1990;64(6):385-387.
In 24 (0.98%) of 2457 patients with congenital heart disease the brachiocephalic vein was in an anomalous position below the aortic arch. This is a much higher proportion of such cases than reported so far. This high frequency may arise from differences in the study population and the method of diagnosis. This venous anomaly was more common in patients with tetralogy of Fallot or ventricular septal defect with pulmonary atresia. Patients with the venous anomaly were more likely to have a right aortic arch. The anomalous course of the brachiocephalic vein from the neck to the junction of the superior vena cava was shown by cross sectional echocardiography. In doubtful cases, Doppler study usually clarified the anatomical arrangement.
PMCID: PMC1224816  PMID: 2271346
16.  Genetic polymorphisms of cytochrome P450 19 and 1B1, alcohol use, and breast cancer risk in Korean women 
British Journal of Cancer  2003;88(5):675-678.
PMCID: PMC2376333  PMID: 12618873
CYP19; CYP1B1; alcohol; breast cancer
17.  Sustained ventricular tachycardia in children after repair of congenital heart disease. 
To investigate an association between surface electrocardiographic (ECG) parameters and sustained ventricular tachycardia (VT) in children after repair of congenital heart disease (CHD), data were obtained and analyzed in three groups (group I, 7 postoperative patients with episode of sustained VT (4 tetralogy of Fallot (TOF), 2 double outlet right ventricle (DORV), 1 truncus arteriosus); group II, 14 children with postoperative TOF not associated with VT; group III, 14 normal children). Mean age at the onset of sustained VT was 129+/-77 months (range 60-232); mean age at corrective surgery, 44+/-33 months (range 10-102); mean follow-up period after surgery, 84+/-74 months (range 20-185); the duration from repair to the onset of sustained VT, range 1-185 months. Compared to group II and III, group I showed longer QRS duration (group I, 137+/-10 msec; group II, 114+/-22 msec; group III, 65+/-12 msec) and shorter corrected J to Tmax interval (group I, 209+/-24 msec; group II, 272+/-44 msec; group III, 249+/-18 msec). QT and corrected QT, J to Tmax interval, and their dispersions in group I and II are significantly different from those of group III. In conclusion, QRS duration and corrected J to Tmax interval could be helpful to predict ventricular tachycardia in postoperative CHD.
PMCID: PMC3054574  PMID: 11289397
19.  Mutations of hepatitis C virus 1b NS5A 2209-2248 amino acid sequence is not a predictive factor for response to interferon-alpha therapy and development of hepatocellular carcinoma. 
Genetic changes between codons 2209 and 2248 of NS5A of genotype 1b hepatitis C virus (HCV-1b) have been reported to be associated with the sensitivity to interferon-alpha (IFN-alpha). The present study was performed to analyze such relationship in Korean patients with chronic hepatitis C and HCV-1b (n=19), including 12 chronic hepatitis C patients treated with IFN-alpha, 3 chronic hepatitis C patients without treatment as controls, and 4 patients with hepatocellular carcinoma (HCC). Two serum samples, before and after the treatment, were analyzed for the mutations by reverse transcription-polymerase chain reaction, cloning and sequencing. The mutations were identified in 32% (6/19), including five intermediate type (1-3 mutations) and one mutant type (4 or more). In 12 patients treated with IFN-alpha, the number of amino acid substitutions in NS5A2209-2248 was not associated with outcome of the treatment. Two HCV isolates with NS5A2209-2248 mutations from HCC patients were intermediate type. These results do not support that the NS5A2209-2248 determines interferon sensitivity of HCV-1b and that the mutations is associated with development of HCC.
PMCID: PMC3054587  PMID: 10719809
20.  A case of Goodpasture's syndrome with massive pulmonary hemorrhage. 
We present a typical case of Goodpasture's syndrome with massive pulmonary hemorrhage and acute deterioration of renal function. A 20-year-old male was admitted due to severe azotemia (blood urea nitrogen 214.7 mg/dL, serum creatinine 30.2 mg/dL) and was treated with emergency hemodialysis. On the 4th hospital day, a sudden onset of pulmonary hemorrhage developed. The circulating level of anti-glomerular basement membrane antibody was then elevated highly, and the kidney biopsy showed crescentic glomerulonephritis and linear deposition of IgG along the glomerular capillary. The patient was treated with intravenous high dose-steroid, oral cyclophosphamide and plasma exchanges. The pulmonary hemorrhage improved with the therapy, however, his renal function did not improve. He is currently on a regular schedule of hemodialysis.
PMCID: PMC3054600  PMID: 10719818
21.  Pulmonary hypertension in a child with juvenile-type autosomal recessive polycystic kidney disease. 
Journal of Korean Medical Science  1999;14(4):451-454.
An 11 year-old girl, whose condition was diagnosed as juvenile-type autosomal recessive polycystic kidney disease (ARPKD) at five years of age, presented with chest pain and dyspnea that had developed suddenly two months previously. Two-dimensional echocardiography, Doppler study and cardiac catheterization confirmed pulmonary hypertension. The underlying mechanism of the diagnosis was not defined. Two and a half months after the onset of symptoms, the patient died of pulmonary hypertensive crisis. Careful regular checks of cardiopulmonary status using two-dimensional echocardiography and Doppler should be considered for the early detection of pulmonary hypertension even in an asymptomatic patient with juvenile-type ARPKD.
PMCID: PMC3054411  PMID: 10485628
22.  Adenovirus-mediated p53 tumor suppressor gene therapy against subcutaneous HuH7 hepatoma cell line nodule of nude mice. 
Journal of Korean Medical Science  1999;14(3):271-276.
Mutations of the tumor-suppressor gene p53 have been found in 30-50% cases of hepatocellular carcinoma (HCC). In this study, E1-negative adenoviral vector encoding wild-type p53 under the control of the human cytomegalovirus promoter (AdCMV-p53w) was constructed to evaluate its therapeutic efficacy against tumor nodules developing after injection of HuH7 cell lines in ten nude mice. When each nodule had reached 10 mm in perpendicular diameter, 1.5 x 10(8) pfu of AdCMV-p53w per session was injected intratumorally as follows: In group I (n=3), five sessions were injected every other day. In group II (n=3), only one session. Group III (n=4) as negative controls. The mice were sacrificed at 28 days post AdCMV-p53w injection. Tumor growth was significantly suppressed and delayed in group I and II compared to group III as compared by tumor volume at the end of observation. These results suggest that AdCMV-p53w may not only be effective in treating HCCs expressing mutant p53, but also useful as a local injectable gene therapy.
PMCID: PMC3054385  PMID: 10402169
23.  Monitoring antibody titers to recombinant Core-NS3 fusion polypeptide is useful for evaluating hepatitis C virus infection and responses to interferon-alpha therapy. 
Journal of Korean Medical Science  1999;14(2):165-170.
To evaluate the clinical feasibility of the antibody titer against a chimeric polypeptide (named Core 518), in which a domain of Core and NS3 of hepatitis C virus (HCV) was fused, ELISA was performed in a total of 76 serum samples. Each serum was serially diluted using two-fold dilution method with distilled water into 10 concentrations. They were all positive for second generation anti-HCV assay (HCV EIA II; Abbott Laboratories). Genotyping RT-PCR, quantitative competitive RT-PCR, and RIBA (Lucky Confirm; LG Biotech) were also assayed. Anti-Core 518 antibody was detected in x 12800 or higher dilutions of sera from 35 of 43 chronic hepatitis C (81.4%) and nine of 16 hepatocellular carcinoma sera (56.3%), one of four cirrhosis (25%), 0 of four acute hepatitis C, and one of nine healthy isolated anti-HCV-positive subjects (p=0.0000). The anti-Core 518 antibody titers were well correlated with the presence of HCV RNA in serum (p=0.002). The anti-Core 518 antibody titers decreased significantly in nine of ten responders to IFN-alpha treatment. Monitoring anti-Core 518 titers may be helpful not only for differentiating the status of HCV infection among patients with various type C viral liver diseases, but also for predicting responses to IFN-alpha treatment.
PMCID: PMC3054362  PMID: 10331562
24.  Atypical pulmonary artery sling with diffuse-type pulmonary arteriovenous fistula. 
The case of a cyanotic infant with a rare combination of atypical pulmonary artery sling, imperforate anus, absence of the left kidney, interruption of the inferior vena cava, left side hemihypertrophy and diffuse-type pulmonary arteriovenous fistula is described. The clinical features were confusing, because of compounding abnormalities involving the respiratory tract and pulmonary circulation. The diagnostic approach to the etiology of cyanosis is discussed and the embryonic origin of pulmonary artery sling is reviewed.
PMCID: PMC3054176  PMID: 10102529
25.  Experience of orthotopic liver transplantation in 11 patients with liver cirrhosis from Korea: medical factors affecting outcome. 
Journal of Korean Medical Science  1998;13(3):299-305.
Orthotopic liver transplantation (OLT) has evolved to become a standard treatment of choice for end-stage liver diseases. The present study was performed to evaluate the peri-operative medical factors affecting transplantation outcome and to determine if patients with type B viral cirrhosis were acceptable for OLT. A total of 11 patients with end-stage cirrhosis, who have received OLT in Kangnam St. Mary's Hospital since May 1993, included 8 HBV-related cases, 1 Hepatitis C Virus (HCV)-related case, and 2 non-B, non-C cases. One-year cumulative survival rate by Kaplan-Meier method was 43.7%. Factors significantly associated with 1-year survival of the recipients during pre-OLT period were performance status and modified Pugh-Child score (p=0.015 and p=0.015, respectively). Among those 4 patients who lived longer than 1 year, 3 of 4 patients with HBsAg-positive had no HBV re-infection with our protocol. These results suggest that, to improve the outcome of OLT in cirrhosis patients, transplantation should be performed in the stage when patients maintain better performance and hepatic functional reserve during the end-stage of liver cirrhosis. In addition, patients with cirrhosis caused by HBV infection may be indicated for OLT, because HBV re-infection is preventable effectively with a high-dose hepatitis B immunoglobulin protocol.
PMCID: PMC3054499  PMID: 9681810

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