Full-length sequence and functional analysis of hepatitis B virus genome in a virus carrier: a case report suggesting the impact of pre-S and core promoter mutations on the progression of the disease.

In chronic hepatitis B virus (HBV) infection, the quiescent immunotolerant phase evolves into the immunoactive phase. The aim of the present study was to clarify the virological alterations relevant to progression. Serial serum samples obtained from a patient with HBV during long-term follow-up were analysed by sequencing of the full-length HBV-DNA using polymerase chain reaction (PCR). In addition, PCR products of HBV genome from each serum sample were transfected into HuH-7 human hepatoma cells for the functional analysis of the transfected viral genomes. Based on the HBV-DNA sequence analysis, the patient had the genotype C virus, and the mutant HBV with common core promoter mutations (T(1762)A(1764)) and deletion of the pre-S region responsible for large surface protein transcription emerged before the onset of hepatitis. When the vigorous host immune response developed (indicated by the flare-up of hepatitis), the mutant HBV containing common core promoter mutations and another pre-S deletion causing lack of the surface protein promoter became predominant. The HBV-DNA sequences, other than pre-S and core promoter regions were identical to the wild-type sequence throughout the study. Transfection of PCR products containing the mutant HBV sequences resulted in increased amounts of intracellular replicative intermediates but the decreased secretion of HBsAg and HBeAg into culture media, suggesting accumulation of nonenveloped viral core particles within the cells. These results indicate that pre-S deletion and core promoter mutations may participate cooperatively in progression of the disease.

Geranylgeraniol, an intermediate product in mevalonate pathway, induces apoptotic cell death in human hepatoma cells: death receptor-independent activation of caspase-8 with down-regulation of Bcl-xL expression.

Geranylgeraniol (GGOH), an intermediate of mevalonate metabolism, is known to induce apoptosis in various lines of cancer cells. The present study was undertaken to clarify the signaling pathways of apoptosis induced by GGOH in human hepatoma cells. HuH-7 human hepatoma cells were incubated in the absence or presence of GGOH. Activation of caspase-8 /-9 /-3 in HuH-7 cells was found after 8 h treatment with GGOH, at which time DNA fragmentation and loss of mitochondrial transmembrane potential (Deltaphim) occurred. HuH-7 cells do not express Bcl-2; however, down-regulation of Bcl-xL expression preceded activation of the caspase cascade in GGOH-treated HuH-7 cells, while Bax expression was not changed by GGOH treatment. Addition of caspase inhibitors restored the decreased cell viability of HuH-7 cells by GGOH, including Deltaphim, to the baseline level, which indicated that caspase triggers mitochondria-dependent apoptotic pathways in GGOH-treated HuH-7 cells. Similarly, GGOH-mediated apoptosis of HuH-7 cells was clearly prevented by coadministration of ursodeoxycholic acid (UDCA), which led to restoration of the level of Bcl-xL expression. Activation of caspase-8 /-9 /-3, as well as Deltaphim, by GGOH treatment was suppressed by addition of UDCA. Our results indicate that activation of the caspase cascade initiating from caspase-8, which could be accelerated by down-regulation of Bcl-xL expression, plays a key role in an apoptotic process induced by GGOH in human hepatoma cells.

A long-term follow-up analysis of serial core promoter and precore sequences in Japanese patients chronically infected by hepatitis B virus.

To investigate the association of hepatitis B virus (HBV) with core promoter mutation (T1762A1764) or precore mutation (A1896) with the clinical course of illness, we analyzed serial core promoter and precore sequences in 22 patients with HBV-associated chronic liver disease who were followed for 12+/-4 years (mean +/- SD). Sixteen of 22 patients were positive for HBeAg at baseline, and 15 of the 16 patients seroconverted to anti-HBe during the observation period. T1762A1764 mutation was detected in 16 of 22 patients, including 11 patients positive for HBeAg, at baseline. During the follow-up period, A1896 mutation emerged in 7 of 16 patients who had the wild-type HBV or only the T1762A1764 mutation at baseline. Sustained remission of hepatitis correlated with the low level of viremia, but did not with type of mutations. These results indicate that HBV with T1762A1764 mutation tends to precede A1896 mutation during the course of infection in Japanese patients with chronic liver disease.

Geranylgeranylacetone induces antiviral gene expression in human hepatoma cells.

Geranylgeranylacetone (GGA), an isoprenoid compound, is used clinically as an anti-ulcer drug. Since some isoprenoids including retinoids have anti-tumor and anti-viral activities in a variety of cell types, we investigated whether GGA could induce anti-viral proteins in human hepatoma cells. The HuH-7 and HepG2 cells were treated with GGA, and expression of anti-viral proteins such as 2'5'-oligoadenylate synthetase (2'5'-OAS) and double-stranded RNA-dependent protein kinase (PKR) in these cells was analyzed. GGA stimulated 2'5'-OAS and PKR gene expression at the transcriptional level through the formation of interferon-stimulated gene factor 3 (ISGF3), which regulates both gene transcription. By Western blotting, GGA induced expression of signal transducers and activators of transcription 1, 2 (STAT1, STAT2) and p48 proteins, components of ISGF3, together with the phosphorylation of STAT1. These results suggest that GGA acts as a potent inducer of anti-viral gene expression by stimulating the ISGF3 formation in human hepatoma cells.

HASTE MR cholangiopancreatography in the evaluation of intraductal papillary-mucinous tumors of the pancreas.

PURPOSE: The aim of this study was to determine the usefulness of MR cholangiopancreatography (MRCP) of intraductal papillary-mucinous tumors. METHOD: Thirteen patients with intraductal papillary-mucinous tumors were examined by breath-hold MRCP using a half-Fourier acquisition single-shot turbo spin echo (HASTE) sequence with a body phased-array coil. RESULTS: Endoscopic retrograde cholangiopancreatography (ERCP) and MRCP completely imaged the entire main pancreatic duct in 12 and in all 13 patients, respectively. ERCP demonstrated the whole opacification of the cystic lesion in only one patient. MRCP depicted the whole of the cystic lesion in all 11 patients who had cystic lesions. ERCP and MRCP source images depicted a communicating duct between the main pancreatic duct and the cystic lesion in 8 and in all 11 patients, respectively. ERCP depicted papillary projections in the main pancreatic ducts in two patients. MRCP source images depicted papillary projections in the main pancreatic ducts or cystic lesions in five patients. CONCLUSION: MRCP may be more useful to reveal the main pancreatic duct, cystic lesion, communicating duct between the main pancreatic duct and cystic lesion, and papillary projections than ERCP in patients with intraductal papillary-mucinous tumors of the pancreas.

Lymphoepithelial cysts of the pancreas: demonstration of lipid component using CT and MRI.

We present two cases of surgically proven lymphoepithelial cyst (LEC) of the pancreas that had a lipid component visualized by CT and MRI. Identification of this component in a pancreatic cystic lesion is a key to favor the diagnosis of LEC or splenic epidermoid cyst over other cystic lesions when the lesion is noted in an elderly patient.

Hepatic lesion detection at MR imaging: a comparative study with four sequences.

PURPOSE: To compare results with the following magnetic resonance (MR) imaging sequences in the detection of focal hepatic lesions: fast spin-echo (SE) before and after administration of superparamagnetic iron oxide (SPIO) particles, fat-suppressed T2-weighted SE, and dynamic gadolinium-enhanced fast low-angle shot (FLASH). MATERIALS AND METHODS: In 26 patients with known malignancy and documented focal liver lesions, 1.0-T MR imaging was performed prior to hepatic resection. All images were reviewed independently by four blinded observers. Sensitivity was calculated for each sequence and for each observer by means of alternative-free-response receiver operating characteristic (ROC) methods. RESULTS: The mean area under the alternative-free-response ROC curve with SPIO-enhanced fast SE (0.85) was significantly greater (P < .02) than that with all other sequences. Detection was significantly improved with SPIO-enhanced fast SE compared with dynamic gadolinium-enhanced FLASH (which was the best of the other three sequences) for all lesions (P < .002) and for malignant lesions (P < .0002). CONCLUSION: Findings with the SPIO-enhanced fast SE sequence improved detection of focal liver lesions and had the highest diagnostic accuracy.

[Construction of an MRI reporting system using the Internet].

Out university hospital, includes a LAN (Local Area Network) and uses network services such as WWW(World Wide Web). We have constructed an MRI diagnostic reporting system on the Internet in which interactive date management was established on WWW by using CGI (Common Gateway Interface) software. Linking database information such as MRI reports with WWW browsers using by CGI provides easy data access to the database and offers hypertext and searching. This system suggests the possibility of creating a cheaper and more flexible network using Internet technology.

Age-related changes in cerebral MR angiography.

Two hundred forty four neurologically normal subjects (118 males and 126 females, aged 7 to 82 yrs.) were evaluated to assess the correlation of the degree of visualization of cerebral arteries on magnetic resonance angiography (MRA) with aging, sex, laterality or lacunar infarctions on magnetic resonance imaging (MRI). A single volume three-dimensional transformation time-of-flight pulse sequence with slab thickness of 115 mm was used to obtain axial, saggital and coronal projection images. A total of 6 arteries including bilateral anterior cerebral arteries (ACAs), middle cerebral arteries (MCAs) and posterior cerebral arteries (PCAs) for every subject were each graded into 8 scores by the degree of visualization of the arteries. Results show that an age-related decline of visualization of the cerebral arteries in ACA (r = -0.603, p < 0.001), MCA (r = -0.452, p < 0.001) and PCA (r = -0.537, p < 0.001). The arteries were better visualized in females than males during the fifth decade (p < 0.01). No substantial relationship was observed between the visualization and sex in the other decades, laterality or lacunar infarctions. Thus, the cerebral MRA showed an age-related decline of visualization of the arteries and a sex-difference of the visualization in the fifth decade, probably due to the decline of the blood flow velocity with aging and a difference in it between females and males in the fifth decade.

Hippocampal volume asymmetry and age at illness onset in males with schizophrenia.

To determine whether there are disturbances of hippocampal volume asymmetry in schizophrenic patients, we obtained contiguous, 1-mm-thick magnetic resonance images in 28 males with chronic schizophrenia and in 28 age-matched healthy males. The schizophrenic patients showed a bilateral reduction in volume of the hippocampal formation (HF; left 7.0%; right 8.7%). This reduction was significantly associated with the severity of disorganization syndrome (P < 0.0005). A significant asymmetry in the HF volume was found in the control subjects (P = 0.006), but not in the patients (P = 0.40). There was a significant positive correlation between the asymmetry index and the patient's age at the onset of schizophrenia (r = 0.46, P = 0.01). Results indicate that a disturbance in the normal asymmetry of the HF may be a characteristic in schizophrenia, particularly in patients with an early onset of the illness.

Retroperitoneal foregut cyst.

A foregut cyst is formed as a result of abnormal budding and pinching of the tracheobronchial tree when bronchial buds develop to form the primitive respiratory tree. Foregut cysts are clinically classified as bronchogenic, esophageal, enterogastric, or ciliated hepatic. We present a foregut cyst that occurred in the retroperitoneum and was difficult to distinguish from other retroperitoneal cystic mass lesions. Magnetic resonance imaging was useful in revealing the cyst's continuity to adjacent organs.

MR imaging during arterial-portography (MR-AP) in the detection of hepatic tumor: comparison with CT-AP.

This study was undertaken to compare the detection rate of hepatic space occupying lesion (SOL)s between computed tomography during arterial portography (CT-AP) and magnetic resonance imaging during arterial portography (MR-AP) and the differences in time intensity curve on MR-AP between HCC, metastatic tumor, FNH, and hemangioma. We performed CT-AP and MR-AP in 17 patients including 14 cases of HCC and one each of metastasis, FNH, and hemangioma. MR-AP was performed by Turbo-FLASH sequence. There was no statistically significant difference between CT-AP and MR-AP in detecting satellite lesions in terms of smallest diameter and number of flow defects (p > 0.05). Hemangioma showed rapid enhancement after the first pass and, consequently, the same enhancement as the hepatic parenchyma. MR-AP was comparable to CT-AP in the detection of hepatic SOLs. Hemangioma showed an enhancement pattern different from those of HCC, metastatic tumor, and FNH, which showed patterns similar to each other.

Reduction in hippocampal formation volume is caused mainly by its shortening in chronic schizophrenia: assessment by MRI.

We performed contiguous, 1 mm thick, magnetic resonance imaging scans in 18 men with chronic schizophrenia and in 18 age-matched healthy subjects to test in living patients the findings of a previous postmortem study. The schizophrenic patients showed bilaterally shortening (left, -6%; right, -9%) and volume reduction (left, -9%; right, -11%) of the hippocampal formation (HF). Volumes of HF correlated positively with HF length in the schizophrenic patients. The reduction in bilateral HF volumes was small after controlling for HF lengths (left, -3%; right, -3%). In schizophrenic patients, significant negative correlations were found bilaterally between the length of HFs and the scores for attention, bizarre behavior, and positive formal thought disorder. The results suggest that the volume reduction seen in the HFs of schizophrenic patients was caused mainly by a shortening of the HF and that these clinical symptoms may be associated with shorter HF length.

A case of retroperitoneal pseudomyxoma.

We experienced a rare case of pseudomyxoma that progressed into the retroperitoneum. This patient presented with complaints of polyuria and back pain. CT and MRI showed a retroperitoneal cystic tumor. Surgical and pathological findings confirmed mucinous cystadenoma of the appendix that reached the posterior space behind the right kidney through the retroperitoneum.

A case with Cushing's syndrome treated with arterial ablation of adrenal gland by absolute ethanol.

Adrenal arterial embolization with absolute ethanol was performed for the treatment of Cushing's syndrome. A 55-year-old woman was admitted to our hospital with complaints of obesity, hypertension, and back pain caused by left adrenal hyperplasia after surgical resection of the right adrenal gland. Therapeutic adrenal arterial embolization was performed by the coaxial technique using absolute ethanol (AE) as an embolic material. No severe complications were encountered during the procedure, and the patient was discharged without symptoms or abnormalities on laboratory tests.

Transarterial internal radiation therapy with I-131 Lipiodol for multifocal hepatocellular carcinoma: immediate and long-term results.

Transarterial internal radiation with I-131 Lipiodol (TAIR) was performed in 21 patients with multifocal hepatic carcinoma. Eight patients were treated by TAIR alone and 13 by combination of TAIR and intraarterial infusion of cis-diamminedichloroplatinum (CDDP) and/or adriamycin mitomycin C oil suspension (ADMOS). TAIR was found effective immediately and long-term. Serum alpha-feto-protein (AFP) levels dropped to 50% or less in 7 of 14 patients. Eleven of 21 patients (52%) showed 50% or greater decrease in tumor size. The overall 1-year survival rate was 43% and 67% in patients who received 50 Gy or greater tumor dose. Lipiodol distribution pattern of the tumor indicated some difference in the prognosis between the scattered pattern and solid pattern. The solid pattern showed a statistically significant better survival rate. Patients treated with TAIR alone versus those treated with TAIR and chemotherapy showed no difference in their survival rate.

[MR imaging during arterio-portography (MR-AP) in the detection of hepatic cancer].

Magnetic resonance imaging during arterio-portography (MR-AP) was performed in 2 patients of hepatic cancer. Low dose of meglumine gadopentetate (4 ml of a 0.5 mmol/L solution) was injected into a superior mesenteric artery during acquisition of a Turbo-FLASH sequence. An increase in liver to lesion contrast was obtained with MR-AP and it is also useful in the late phase to distinguish a flow defect lesion due to portal obstruction from the tumor.