PURPOSE: We measured pulmonary epithelial permeability by Tc-DTPA radioaerosol clearance in patients with diabetes and correlated with the presence of microangiopathy to understand the pathophysiology of pulmonary microangiopathy and evaluate Tc-DTPA radioaerosol clearance as a diagnostic test to assess pulmonary microangiopathy. MATERIALS AND METHODS: We performed ' Tc-DTPA radioaerosol scan in 10 normal subjects, 10 asym-ptomatic smokers, 20 diabetic patients without history of smoking (10 with microangiopathy, 10 without microangiopathy). Tc-DTPA clearance half-time (T1/2) was calculated, then compared with the result of chest radiography and pulmonary function test. RESULTS: Chest radiography and pulmonary function test were normal in all subjects. There were no significant difference of clinical or laboratory characteristics between these groups except age. The diabetic patients with micraangiopathy were significantly older (p<0.05). The T1/2of normal subjects and asyrnptomatic smokers were significantly different (65.2+23.7min vs 39.6+9.8min, p<0.05). For diabetic patients with microangiopathy, the T, was 90 5+46.5min and significantly delayed when compared with those of normals and asymptomatic smokers (p<0.05). However, the T1/2of diabetic patients without microangiopathy, 70.0+12.7 min, was not significantly different from those of normals or asyrnptomatic smokers (p>0.05). No significant correlation was found between the T1/2and spirometric parameters including DLcc>, FVC, FEV>, FEV(/FVC (%) and FEF)5-75g in all subjects, and between the T1/2 and duration of diabetes in diabetic patients. CONCLUSION: Eventhough the influence of age cant be excluded, delayed Tc-DTPA clearance half-time (T1/2)in diabetic patients with microangiopathy indicates decreased pulmonary cspillary permeability as one of the pathophysiologic results of pulmonary microangiopaththy. Further studies are needed in larger number of age matched control and diabetic patients to evaluate the diagnostic efficacy.
Diabetes Mellitus ; Diagnostic Tests, Routine ; Humans ; Permeability ; Radiography ; Respiratory Function Tests ; Smoke ; Smoking ; Technetium Tc 99m Pentetate ; Thorax

The use of radiopharmaceuticals in evaluation of pulmonary tuberculosis may help to resolve difficult diagnostic problems such as discordance between sputum examinations and chest roentgenographic findings. We investigated the usefulness of 99mTc-methoxyisobutylisonitrile(MIBI) scintigraphy in the detection of active pulmonary tuberculosis. Forty-six patients with suspected active pulmonary tuberculosis were studied with sputum smear of AFB, sputum AFB culture, chest X-ray and MIBI scan. MIBI image was obtained 15 and 60 min after intravenous injection of 370MBq(10mCi) 99mTc-MIBI. In 16 patients of them Ga scans were performed in addition to MIBI scan. Repeated MIBI scans were done in 7 patients with active pulmonary tuberculosis after 4~6 months of antituberculous chemotherapy. Thirty-two patients were confirmed as active tuberculosis by sputum culture. Sensitivity of MIBI scan to active tuberculosis was 87.5%(28/32) and MIBI findings were negative in all of 14 patients with inactive disease. Focal uptake of MIBI was dense in the area that was strongly suggested active tuberculous lesions by chest roentgenogram. There was no discordance between MIBI and Ga image in 16 patients. But the uptake areas of Ga images were broader than that of MIBI images. After 4~6 months of antituberculous treatment all repeated MIBI scans revealed negative findings except 1 patient with persistent active pulmonary tuberculosis due to drug resistance. MIBI scan could be used in the detection of active pulmonary tuberculosis as a useful noninvasive diagnostic tool.
Drug Resistance ; Drug Therapy ; Humans ; Injections, Intravenous ; Radionuclide Imaging ; Radiopharmaceuticals ; Sputum ; Thorax ; Tuberculosis ; Tuberculosis, Pulmonary*

BACKGROUND/AIMS: The immunoregulatory molecules programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) are associated with the dysfunction of antiviral effector T-cells, which leads to T-cell exhaustion and persistent viral infection in patients with chronic hepatitis C and chronic hepatitis B. Little is known about the role of PD-1 and CTLA-4 in patients with symptomatic acute hepatitis A (AHA). METHODS: Peripheral blood mononuclear cells were isolated from seven patients with AHA and from six patients with nonviral acute toxic hepatitis (ATH) during the symptomatic and convalescent phases of the respective diseases; five healthy subjects acted as controls. The expression of PD-1 and CTLA-4 on T-cells was measured by flow cytometry. RESULTS: PD-1 and CTLA-4 expression during the symptomatic phase was significantly higher in the T-cells of AHA patients than in those of ATH patients or healthy controls (PD-1: 18.3% vs 3.7% vs 1.6%, respectively, p<0.05; CTLA-4: 23.5% vs 6.1% vs 5.9%, respectively, p<0.05). The levels of both molecules decreased dramatically during the convalescent phase of AHA, whereas a similar pattern was not seen in ATH. CONCLUSIONS: Our findings are consistent with a viral-protective effect of PD-1 and CTLA-4 as inhibitory molecules that suppress cytotoxic T-cells and thereby prevent the destruction of virus-infected hepatocytes in AHA.
Acute Disease ; Adult ; CTLA-4 Antigen/*genetics ; Case-Control Studies ; Female ; Flow Cytometry ; Hepatitis/genetics ; Hepatitis A/*genetics/virology ; Hepatitis A Virus, Human ; Humans ; Male ; *Phenotype ; Programmed Cell Death 1 Receptor/*genetics ; T-Lymphocytes/metabolism

Liver cirrhosis is one of the major complications of hepatitis C virus (HCV) infection, but the mechanisms underlying HCV-related fibrogenesis are still not clear. Although the roles of HCV core protein remain poorly understood, it is supposed to play an important role in the regulation of cellular growth and hepatocarcinogenesis. The aim of this study was to examine the role of HCV core protein on the hepatic fibrogenesis. We established an in vitro co-culture system with primary hepatic stellate cell (HSC) isolated from rats, and a stable HepG2-HCV core cell line which had been transfected with HCV core gene. The expressions of fibrosis-related molecules transforming growth factor beta1 (TGF-beta1), transforming growth factor b receptor II (TGF beta RII), alpha-smooth muscle actin (alpha-SMA) and connective tissue growth factor (CTGF) were analyzed via histological or molecular methods. In addition, the expression levels of matrix metaloprotinase-2 (MMP-2) and collagen type I (Col I) from the co-cultured media were measured by zymogram and ELISA, respectively. The expressions of alpha-SMA, TGF-beta1, Col I, TGF beta RII and MMP-2 were significantly increased in the co-culture of stable HepG2-HCV core with HSC. Moreover, the significant increases of CTGF and TGF-beta1 in the HCV core-expressing cells were observed by either Northern or Western blot analysis. These results suggest that HCV core protein may contribute to the hepatic fibrogenesis via up-regulation of CTGF and TGF-beta1.
Actins/metabolism ; Animals ; Cell Line, Tumor ; Cells, Cultured ; Coculture Techniques ; Collagen Type I/metabolism ; Gelatinase A/metabolism ; Immediate-Early Proteins/*biosynthesis ; Intercellular Signaling Peptides and Proteins/*biosynthesis ; Liver/metabolism/*pathology ; Liver Cirrhosis/*metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Receptors, Transforming Growth Factor beta/metabolism ; Research Support, Non-U.S. Gov't ; Transforming Growth Factor beta/*metabolism ; Up-Regulation ; Viral Core Proteins/genetics/*metabolism

Hepatitis B virus (HBV) is one of the major causative agents of chronic liver diseases in Korea. HBV has been classified into 8 genotypes by a divergence of >8% in the entire genomic sequence, and have distinct geographic distributions. There are limited data on the relevance between HBV genotypes and clinical outcomes in Korea. To investigate the clinical feature relating to HBV genotype in Korea, a total 120 serum samples with HBsAg (65 from Seoul and 55 from the other city in Korea) were obtained from each 30 chronic HBV carriers with asymptomatic carrier (ASC), chronic hepatitis (CH), liver cirrhosis (LC) and hepatocellular carcinoma (HCC). HBV genotype was determined by either enzyme-linked immunosorbent assay (ELISA) using monoclonal antibodies against genotype-specific epitopes in the preS2-region or the direct sequencing of small S gene. HBV genotypes were determined in 105 (87.5%) of 120 samples. HBV genotype C was identified in all HBV carriers with ASC, CH, LC, and HCC. Genotypes A, B, D, E, F and G were not detected in any of them. Genotype C HBV prevails predominantly among chronic carriers of the virus in Korea, irrespective of their clinical stages of liver disease and geographic origin.
Carrier State/*epidemiology/*virology ; Comorbidity ; Female ; Genotype ; Hepatitis B virus/*genetics/isolation and purification ; Hepatitis B, Chronic/*epidemiology/*virology ; Humans ; Korea/epidemiology ; Liver Diseases/*epidemiology/*virology ; Male ; Middle Aged ; Prevalence ; Research Support, Non-U.S. Gov't ; Risk Assessment/methods ; Risk Factors

The current best treatment for HCV infection is combination therapy with PEG-interferon and ribavirin. This combination therapy has markedly increased the number of sustained virologic responders but is associated with various side effects, especially hematological abnormalities. We recently experienced a 45-year-old man who developed PEG-interferon induced autoimmune hemolytic anemia (AIHA) and retinal premacular hemorrhage. The worsening hemolysis after ribavirin withdrawal and exclusion of other causes implicated PEG-interferon as the cause of the AIHA. To the best of our knowledge, this is the first case reported from Korea. Treatment with PEG-interferon requires careful follow-up, as it can induce or exacerbate autoimmune diseases.
Anemia, Hemolytic, Autoimmune ; Autoimmune Diseases ; Follow-Up Studies ; Hemolysis ; Hemorrhage ; Hepatitis ; Hepatitis C ; Hepatitis C, Chronic ; Humans ; Korea ; Middle Aged ; Retinal Hemorrhage ; Retinaldehyde ; Ribavirin

Gastrointestinal stromal tumors (GIST) are generally located in the stomach and small intestine, and they present most with commonly abdominal pain. However, the duodenum is an unusual location and is commonly associated with gastrointestinal bleeding. A 51-year-old female was admitted for a 15-day history of melena and malaise. A cystic mucosal lesion featuring an isolated duodenal varix was observed by gastroduodenoscopy. Abdominal CT revealed a tortuous vascular structure at the posterior wall of the duodenum. Endoscopic Histoacryl injection therapy at the cystic mucosal lesion and a duodenal segmental resection were performed. The procedure was successful. Microscopic observation revealed GIST. We report a case of a duodenal GIST mimicking an isolated duodenal varix.
Abdominal Pain ; Duodenum ; Enbucrilate ; Female ; Gastrointestinal Stromal Tumors* ; Hemorrhage ; Humans ; Intestine, Small ; Melena ; Middle Aged ; Stomach ; Tomography, X-Ray Computed ; Varicose Veins*

BACKGROUND: Liver cirrhosis is characterized by fibrous scarring and hepatocellular regeneration. Matrix metalloproteinases (MMPs) comprise a family of zinc-dependent enzymes that degrade the extracellular matrix (ECM) components. This study examined whether or not gene delivery of human MMP-3 can attenuate established liver cirrhosis in a rat. METHODS: Rat liver cirrhosis was induced by an intraperitoneal injection of dimethylnitrosamine (DMN) three times a week for 8 weeks. The rats were infected once with either a recombinant adenovirus, AdMMP3.GFP, or a control adenovirus, Ad.GFP, into a portal vein and followed up for 3 weeks. In the rat liver tissues, the collagen content, histopathology and immunohistochemical staining were measured. RESULTS: Liver fibrosis in the DMN induced cirrhotic rat was attenuated along with a diminished hydroxyproline content and increased dried liver weight after the gene delivery of AdMMP3.GFP. In addition, the number of activated hepatic stellate cells was lower whereas the proliferation of hepatocytes, which was confirmed by immunohistochemical staining using anti-proliferating cell nuclear antigen (PCNA) antibody, was observed in the AdMMP3.GFP infected rats, suggesting that human MMP-3 stimulated hepatocyte proliferation. CONCLUSIONS: These results suggest that the gene transfer of human MMP-3 in the liver attenuates established fibrosis and induces hepatocyte proliferation. Therefore, gene therapy using MMP-3 in liver cirrhosis might be a promising therapeutic option in the future.
Adenoviridae* ; Animals ; Cicatrix ; Collagen ; Dimethylnitrosamine ; Extracellular Matrix ; Fibrosis ; Genetic Therapy* ; Hepatic Stellate Cells ; Hepatocytes ; Humans ; Hydroxyproline ; Injections, Intraperitoneal ; Liver Cirrhosis* ; Liver* ; Matrix Metalloproteinases ; Models, Animal* ; Portal Vein ; Rats* ; Regeneration

Background/Aims: The role of hepatitis B virus (HBV) integration into the host genome in hepatocarcinogenesis following hepatitis B surface antigen (HBsAg) seroclearance remains unknown. Our study aimed to investigate and characterize HBV integration events in chronic hepatitis B (CHB) patients who developed hepatocellular carcinoma (HCC) after HBsAg seroclearance.
Methods: Using probe-based HBV capturing followed by next-generation sequencing technology, HBV integration was examined in 10 samples (seven tumors and three non-tumor tissues) from seven chronic carriers who developed HCC after HBsAg loss. Genomic locations and patterns of HBV integration were investigated.
Results: HBV integration was observed in six patients (85.7%) and eight (80.0%) of 10 tested samples. HBV integration breakpoints were detected in all of the non-tumor (3/3, 100%) and five of the seven (71.4%) tumor samples, with an average number of breakpoints of 4.00 and 2.43, respectively. Despite the lower total number of tumoral integration breakpoints, HBV integration sites in the tumors were more enriched within the genic area. In contrast, non-tumor tissues more often showed intergenic integration. Regarding functions of the affected genes, tumoral genes with HBV integration were mostly associated with carcinogenesis. At enrollment, patients who did not remain under regular HCC surveillance after HBsAg seroclearance had a large HCC, while those on regular surveillance had a small HCC.
Conclusions The biological functions of HBV integration are almost comparable between HBsAg-positive and HBsAgserocleared HCCs, with continuing pro-oncogenic effects of HBV integration. Thus, ongoing HCC surveillance and clinical management should continue even after HBsAg seroclearance in patients with CHB.

Budd-Chiari syndrome (BCS) is defined by the obstruction of the hepatic venous outflow between the small hepatic veins and the junction of the inferior vena cava (IVC) with the right atrium. BCS with IVC obstruction occasionally progresses to hepatocellular carcinoma (HCC). Here, we report the case of a patient with HCC arising from a cirrhotic liver with BCS, in whom the hepatic portion of the IVC was obstructed, and who had a favorable outcome with a multidisciplinary approach and IVC balloon angioplasty.