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Biomedical subjects

H Nagano

Publications and source records attributed to H Nagano.

At least 19 recordsLinked to original sources
PubMed2003

The movement protein gene is involved in the virus-specific requirement of the coat protein in cell-to-cell movement of bromoviruses.

Brome mosaic virus (BMV) requires the coat protein (CP) for cell-to-cell movement whereas Cowpea chlorotic mottle virus (CCMV), from the same genus, does not. Chimeric viruses created by exchanging the movement protein (MP) gene between the viruses can move from cell to cell. We show that interference in CP expression impaired the movement of the chimeric CCMV with the BMV MP gene but not of the chimeric BMV with the CCMV MP gene. We thus conclude that the MP gene plays a crucial role in determination of the virus-specific CP requirement in bromovirus cell-to-cell movement.

Amino Acid Sequence↗
PubMed2002

Optical intersubband transitions and femtosecond dynamics in Ag/Fe(100) quantum wells.

The optical intersubband transitions and femtosecond dynamics of electrons in quantum well states in Ag/Fe(100) are investigated by interferometric time-resolved two-photon photoemission. The quantum well wave functions and transition probabilities are evaluated from the two-photon photoemission resonance energies and intensities using an extended phase accumulation model. Direct femtosecond pump-probe correlation measurements elucidate the importance of interfaces in confined structures.

Journal Article↗
PubMed2002

An immunohistochemical study of cyclooxygenase (COX)-2 expression in endocrine tumors of the pancreas.

Cyclooxygenase (COX) is a key rate-limiting enzyme in prostaglandin biosynthesis. There are two isoforms of COX, referred to as COX-1 and COX-2. COX-2, an inducible form of COX, is found to be overexpressed in various neoplasms and is believed to play an important role in tumorigenesis and tumor development. In this study, we investigated expression of the COX-2 protein in human endocrine tumors of the pancreas (N=23; 6 insulinomas, one glucagnoma, 2 gastrinomas, and 14 non-functioning tumors) using immunohistochemistry. Strong COX-2 expression was confirmed in normal islet tissue as previously reported. COX-2 immunoreactivity was detected in 65% (15 out of 23) of these tumors with a moderate to strong intensity. In all nine functioning tumors, COX-2 expressions were preserved with the weak or strong intensity. In contrast, COX-2 was present in 6 out of 14 nonfunctioning tumors. The correlation between COX-2 expression and their function was significant (p<0.05). We found that expression of this enzyme was detected in 11 out of 15 benign tumors and in 4 out of 8 malignant tumors, respectively. Our results suggest that COX-2 may play an important role in the endocrine function of islet tumors. Additionally, malignancy was not related to COX-2 expression.

Adult↗
PubMed2001

Angiosarcoma of the breast: report of a case and its findings of MRI.

A 67-year-old woman with angiosarcoma of the left breast is presented. Physical findings showed a hard mass in the left breast with skin discoloration and erythema. Mammography showed a high density shadow in the mass without microcalcification and spicula. On ultrasonography, a hypoechoic mass with an ill-defined boundary was detected. On MRI, the tumor had low signal intensity on T1-weighted images, and higher signal intensity on T2-weighted images. MRI with Gd-DTPA images showed higher signal intensity on T1-weighted images with relatively lower intensity in the central area of the tumor. The artery supplying the tumor derived from the left inner thoracic artery and was visualized on three-dimensional dynamic MRI angiography. Initially misdiagnosed as inflammatory breast cancer, an arterial injection of CPA (100 mg) and 5-FU (500 mg) had been performed preoperatively. The definitive diagnosis of angiosarcoma was established by intraoperative frozen section examination. She underwent modified radical mastectomy and is now free of recurrence. This case emphasizes the difficulties in the clinical diagnosis of angiosarcoma of the breast.

Aged↗
PubMed2001

Prednisolone suppresses ischemia-reperfusion injury of the rat liver by reducing cytokine production and calpain mu activation.

BACKGROUND: We investigated the effects of prednisolone on cytokine production and calpain mu activation during hepatic ischemia-reperfusion (IR) injury. METHODS: The hilar area of the left lateral and median lobes of rat liver was clamped for 60 min. Prednisolone was administered at 1.0, 3.0, or 10 mg/kg at 30 min before ischemia. In addition to biochemical and microscopic analyses, IL-beta and TNF-alpha production was evaluated by RT-PCR. Calpain mu activation and talin degradation were determined by Western blotting, using specific antibodies. RESULTS: In the control and prednisolone (1.0 mg/kg) groups, serum AST and ALT levels were elevated, and cell membrane bleb formation was observed after 2 h of reperfusion. Moreover, calpain mu activation, talin degradation, and overexpression of IL-beta and TNF-alpha mRNAs were detected. Infusion of prednisolone at 3.0 or 10 mg/kg significantly suppressed biochemical and microscopic changes. At 10 mg/kg, prednisolone markedly suppressed IL-beta and TNF-alpha transcription and calpain mu activation and talin degradation, consistent with the improved 7-day survival after total hepatic ischemia (75% vs. 25% in control group, P = 0.039). CONCLUSIONS: Cytoprotective effect of prednisolone in hepatic IR injury was closely associated with suppression of IL-beta/TNF-alpha production and calpain mu activation.

Alanine Transaminase↗
PubMed2001

Activation of c-Src gene product in hepatocellular carcinoma is highly correlated with the indices of early stage phenotype.

BACKGROUND/AIMS: The aim of this study was to investigate whether c-Src is involved in carcinogenesis and progression of human hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma. METHODS: We designed an immunohistochemical study using Clone 28, an antibody that specifically recognizes the activated form of c-Src. RESULTS: Hepatocytes in normal liver, chronic hepatitis with or without cirrhosis, atypical adenomatous hyperplasia, as well as bile ductular cells, and infiltrating mononuclear cells were all negative for immunohistochemical staining for the activated c-Src. Among 87 cases of HCC tested, 40 (46%) were positively stained for the activated c-Src, and this positive staining was inversely correlated with the Ki-67 labeling index (LI) (P = 0.0031), intrahepatic metastasis (P = 0.0099), TNM stage (P = 0.0062), alpha-fetoprotein (P = 0.0103) and epidermal growth factor-receptor expression (P = 0.0153). Positive staining for the activated c-Src was more frequently observed in well- or moderately-differentiated carcinoma (P = 0.0256). In multivariate analysis, the activated c-Src expression was independently related to the Ki-67 LI (P = 0.0197). In contrast to positive staining in HCC, cholangiocarcinoma were classified as negative in all 19 cases examined. CONCLUSIONS: These results strongly suggest the involvement of activated c-Src in early stages of HCC, and suggest that cholangiocarcinoma might employ different signaling mechanisms.

Carcinoma, Hepatocellular↗
PubMed2001

Various scoring systems evaluating histologic features of chronic hepatitis C treated with interferon.

Various scoring systems for chronic hepatitis have been proposed; however, there is no standard scoring system for studies of interferon (IFN) therapy in patients with chronic hepatitis C. The aims of this study were to determine the most useful system reflecting histologic changes in biopsy specimens from complete responders and predicting the efficacy of IFN therapy. Patients with chronic hepatitis C were administered IFN-alpha for 6 months. Forty-six patients were included in this study and categorized as complete responders (n = 15), partial responders (n = 24), and nonresponders (n = 7) according to viral and biochemical responses to the therapy. Biopsy specimens obtained from each patient before and after treatment were evaluated under 3 different systems: Histological Activity Index (HAI), modified HAI, and Scheuer classification. Complete responders showed considerable improvement in both grade and stage on the modified HAI and Scheuer classifications. On the HAI, a considerable improvement was observed in grade but not in stage. No significant change was observed in partial responders or nonresponders on any system. Prediction of complete response was not possible under any system, but the pretreatment score reflecting piecemeal necrosis on any 1 of the 3 classifications and the fibrosis score on Scheuer classification were predictors of nonresponse. The modified HAI system and Scheuer classification were amply useful in evaluating histologic changes in complete responders. Scores higher than 4 of the categories reflecting piecemeal necrosis on any system and fibrosis scores of 3 or 4 on Scheuer classification predicted nonresponse to IFN therapy.

Adult↗
PubMed2001

Differential expression of cyclooxygenase-2 (COX-2) in human bile duct epithelial cells and bile duct neoplasm.

It is well known that chronic inflammatory conditions involving the bile ducts predispose to the development of bile duct carcinoma, although the relationship between chronic inflammation and malignant transformation is unclear. In this study, by combining immunohistochemistry and computer imaging techniques, we quantified and compared the cyclooxygenase-2 (COX-2) protein expression levels of epithelial cells according with their histopathological backgrounds. This technique revealed that the highest levels of COX-2 were expressed in bile duct carcinoma cells, mainly in cytoplasm, and the expression pattern was homogenous and abundant. Moderate levels of COX-2 protein expression were also observed in noncancerous epithelial cells with inflammatory reaction, but the staining intensity was heterogeneous among the positive cells exhibiting inflammation. In contrast, only scattered weak reactivity of COX-2 protein was observed in the noncancerous bile duct epithelial cells without inflammatory reaction. Moreover, bile duct epithelial cells in primary sclerosing cholangitis (PSC) showed very strong expression of COX-2 protein, that was comparable with carcinoma cells. On the other hand, primary biliary cirrhosis (PBC) epithelial cells showed moderate levels of COX-2 expression. In addition, specific COX-2 inhibitors, JTE-522 and NS-398, directly inhibited the growth of 4 bile duct carcinoma and 1 gall bladder carcinoma cell lines that expressed COX-2 protein, in vitro. These data suggest that COX-2 expression might regulate carcinogenesis of bile duct epithelial cells in inflammatory regions and tumor progression in this cancer. The data also suggest that COX-2 selective inhibitors might have therapeutic effects not only on bile duct carcinoma, but other hepatobiliary carcinomas.

Animals↗
PubMed2001

Conversion in the requirement of coat protein in cell-to-cell movement mediated by the cucumber mosaic virus movement protein.

Plant viruses have movement protein (MP) gene(s) essential for cell-to-cell movement in hosts. Cucumber mosaic virus (CMV) requires its own coat protein (CP) in addition to the MP for intercellular movement. Our present results using variants of both CMV and a chimeric Brome mosaic virus with the CMV MP gene revealed that CMV MP truncated in its C-terminal 33 amino acids has the ability to mediate viral movement independently of CP. Coexpression of the intact and truncated CMV MPs extremely reduced movement of the chimeric viruses, suggesting that these heterogeneous CMV MPs function antagonistically. Sequential deletion analyses of the CMV MP revealed that the dispensability of CP occurred when the C-terminal deletion ranged between 31 and 36 amino acids and that shorter deletion impaired the ability of the MP to promote viral movement. This is the first report that a region of MP determines the requirement of CP in cell-to-cell movement of a plant virus.

Bromovirus↗
PubMed2001

Significance of serum matrix metalloproteinases and their inhibitors on the antifibrogenetic effect of interferon-alfa in chronic hepatitis C patients.

OBJECTIVE AND METHODS: The imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) is considered to be an important determination of deposition and breakdown of the extracellular matrix. To investigate the antifibrogenetic effect of interferon-alpha (IFN-alpha) treatment on factors regulating hepatic fibrosis, serum MMP-1, MMP-2, TIMP-1 and TIMP-2 levels were measured by the one-step sandwich enzyme immunoassay in 27 patients with chronic hepatitis C and compared with the histological status of the patients before and at the end of treatment. RESULTS: After 6 months of IFN-alpha treatment, the histological status of liver fibrosis showed improvement in 9 patients (IF group) and no change or a worsening in 18 patients (NIF group). Compared with pretreatment levels, in the IF group, IFN treatment caused a significant increase in the MMP-1/TIMP-1 ratio. In the NIF group, however, the MMP-1/TIMP-1 ratio tended towards a decrease; moreover, there was not only a significant increase in TIMP-2 levels but also a tendency towards an increase in TIMP-1 levels. CONCLUSION: These results suggested that an elevated MMP-1/TIMP-1 ratio may ameliorate liver fibrosis by interferon in cases of chronic hepatitis C, whereas elevated levels of TIMP-1 and TIMP-2 might impede improvement.

Antifibrinolytic Agents↗
PubMed2001

Effects of medium-chain fatty acids on intracellular calcium levels and the cytoskeleton in human intestinal (Caco-2) cell monolayers.

The effects of medium-chain fatty acids (MCFA) on intracellular calcium (Ca2+) levels and actin filaments in the Caco-2 monolayer were investigated. A site-dependent increase in intracellular Ca2+ levels caused by decanoic acid (C10) at 13 mM was observed by confocal laser scanning microscopy. The area in which the intracellular Ca2+ levels was increased was measured by image analysis, and increased to 11% of the total area of the monolayer within 1 minute. This was maintained for 5 minutes, and decreased thereafter. The other MCFAs did not significantly increase the intracellular Ca2+ levels. Obvious morphological changes of actin filaments were induced by only C10 among C8-C14. The area in which actin filaments were depleted was also quantified, and the increase in area became significant after 40 minutes. The area of the actin-depleted spot corresponded to the area occupied by 5 to 10 cells as well as that in which the intracellular Ca2+ level was increased. The effectiveness of only C10 suggested that the mechanism of the absorption enhancement by C10 would be different from that by the other MCFAs, or that C10 has some additional physiological functions although the mechanism of the enhancement is the same as for the other MCFAs.

Actins↗
PubMed2001

Clinical application of quantitative analysis for detection of hematogenous spread of hepatocellular carcinoma by real-time PCR.

In order to detect a hematogenous spread of tumor cells in patients with hepatocellular carcinoma, reverse transcription-polymerase chain reaction assay has been used. In this study, we quantified alpha-fetoprotein (AFP) messenger RNA by real-time PCR approach using LightCyclertrade mark technique. AFP messenger RNA in the blood from 23 hepatocellular carcinoma patients undergoing hepatic resection, 31 healthy volunteers, 10 patients with liver cirrhosis and 5 patients underwent hepatectomy except for hepatocellular carcinoma was quantitated. In the real-time PCR, fluorescence was undetectable in any of the controls. On the contrary, fluorescent signals were detected in 10 out of 39 blood specimens collected from 23 HCC patients. AFP-positive status was significantly associated with the existence of multiple intrahepatic nodules. Out of 8 cases with AFP-positive status, intra- and/or extra-hepatic recurrence has been observed in 3 cases. The quantities of AFP messenger RNA in these 3 cases were relatively high among 8 cases with AFP-positive status. AFP messenger RNA was detectable by newly developed real-time PCR approach with LightCycler and it is suggested that this approach could be applicable in detection of small amounts of tumor cells in the blood of HCC patients.

Biomarkers, Tumor↗
PubMed2001

Human stomach-specific gene, CA11, is down-regulated in gastric cancer.

To reveal the implication in gastric cancer pathogenesis of the novel human gene referred to as CA11, which was recently isolated by a differential display technique using normal gastric mucosa and gastric cancer tissue, we examined CA11 expression in 50 primary gastric cancers and also introduced the CA11 gene into gastric cancer cells. RNA dot blot analysis against various human organs and developmental stages demonstrated that CA11 was intensively expressed especially in normal stomach tissue. Northern blot analysis showed that expression of the CA11 gene in cancer tissue was down-regulated compared with normal tissue. Semi-quantitative RT-PCR also demonstrated that CA11 gene expression was decreased in 41 out of 50 (82%) of the gastric cancer tissues, when compared with normal stomach tissues, while no relationship was found between CA11 expression and various clinicopathological characteristics including histological type, depth of invasion, lymph node metastasis, and clinical stage. Immunohistochemical analysis with anti CA11 antibody showed that CA11-positive staining was observed in the surface regions of normal gastric epithelium, but was found faintly or not at all in cancer tissues. CA11 transfected MKN28 cells also displayed a marked decrease in the number of colony formations when compared to double normal controls. These findings suggest that the loss of CA11 expression in gastric tissues may play an important role in gastric carcinogenesis.

Adenocarcinoma↗
PubMed2001

[Significance of liver resection for multiple hepatic metastases from colorectal cancer].

In colorectal cancer, liver metastasis is the most common and most important prognostic factor. To elucidate the significance of liver resection, we examined 72 cases (H2: 29 cases, H3: 43 cases). The 3-year survival rate for H2 and H3 patients was 71.5% and 4.5%, respectively. The liver resection rate in H2 and H3 patients was 58.6% (17/29) and 16.3% (7/43), respectively. In H2 patients the 3-year survival rate of those with liver resection and non-resection was 71.3% and 9.2%, respectively (p < 0.001). However, in H3 patients the 3-year survival rate in liver resection and non-resection patients was 80.0% and 43.9%, respectively (not significant). Many therapies, such as liver resection, hepatic arterial infusion, and systemic chemotherapy, were attempted for patients with hepatic metastases. Our data show that liver resection can prolong the survival of H2 patients only. On the other hand, hepatic arterial infusion therapy prolongs the survival of H3 patients only. Systemic chemotherapy does not prolong the survival of either H2 or H3 patients.

Adult↗
PubMed2001

[A case of postoperative multiple hepatic metastasis from esophageal cancer successfully treated by surgical resection and hepatic arterial infusion chemotherapy].

A 66-year-old male who underwent radical resection for esophageal cancer (stage IV) was diagnosed with multiple hepatic metastasis 1 year and 3 months after the surgery. He underwent hepatic resection and received systemic chemotherapy (FAP: 5-FU, ADR, CDDP), as the post-operative adjuvant therapy. One year and 3 months later, there was a huge recurrence in the residual liver and hepatic arterial infusion chemotherapy (FAP) was performed. The recurrent lesion disappeared completely after 3 sessions of arterial infusion chemotherapy. The arterial infusion chemotherapy was continued in the outpatient clinic and the recurrent lesion is well controlled. At present, this patient has returned to social life, 2 years and 3 months after the hepatic resection. The utility of hepatic arterial infusion chemotherapy and hepatectomy for postoperative multiple hepatic metastasis from esophageal cancer was shown in the present case.

Aged↗
PubMed2001

[A patient with hepatocellular carcinoma and portal vein thrombosis in 1st branch who was treated by transcatheter arterial embolization].

We report a patient with hepatocellular carcinoma (HCC) with portal vein thrombosis in the 1st branch who was treated by transcatheter arterial embolization (TAE) and survived more than 3 years. A 58-year old male was diagnosed as having unresectable massive type HCC in the area of S8 with portal vein thrombosis from the P8 branch to the right portal branch. He was treated by TAE via the anterior branch of right hepatic artery. One week later, localized hepatic infarction in the anterior segment was recognized. Five months later, the portal vein thrombosis had disappeared and become necrotic. After 3 years and 4 months, he died of a relapse of a gastric varix, but with no portal thrombosis and a well controlled intra-hepatic recurrence that was treated by repeated TAE. This case suggests that TAE might be effective for cases of HCC with portal vein thrombosis in the 1st branch, if the liver function and portal flow are suitable.

Carcinoma, Hepatocellular↗
PubMed2000

The inhibitory effect of prostaglandin E1 on oxidative stress-induced hepatocyte injury evaluated by calpain-mu activation.

BACKGROUND: Prostaglandin E1 (PGE1) is known to inhibit ischemia-reperfusion injury of the liver. The calcium-dependent neutral proteinase, calpain-mu, is involved in oxidative stress-induced hepatocyte injury. We investigated the mechanisms of cytoprotection by PGE1, focusing on the elevation of intracellular calcium ([Ca2+]i), activation of calpain-mu, and calpain-mu-mediated activation of protein kinase C-alpha (PKC-alpha). METHODS: Cultured hepatocytes were treated with various amounts of PGE1 (0, 0.1, 1.0, 10, and 100 ng/ml) for 30 min and subsequently with 0.5 mM tert-butyl hydroperoxide (TBHP). Cell injury was evaluated by the release of lactate dehydrogenase. Plasma membrane bleb formation was examined by phase contrast microscopy. Activation of calpain-mu and limited degradation of PKC-alpha was evaluated by Western blotting using antibodies that specifically recognize the amino-terminal regions of calpain-mu and PKC-alpha. [Ca2+]i was measured by confocal microscopy using Fluo-3AM. RESULTS: LDH release from cells treated with 10 ng/ml PGE1 was significantly lower than from untreated cells (135 +/- 12 vs. 258 +/- 18 IU/L, respectively; P < 0.05). Morphologically, many blebs were observed in untreated cells, but very few were seen in those treated with 10 ng/ml PGE1. Western blotting revealed that the amount of activated calpain-mu and [Ca2+]i increased up to 1,300 nM at 35 min after the addition of TBHP (0.5 mmol/L) in control experiments (without PGE1). PGE1 (10 ng/ml) delayed the rise in [Ca2+]i for about 30 min, but did not suppress it completely. PKC-alpha decreased in experiments using PGE1 (10 ng/ml). CONCLUSION: PGE1 exerts its cytoprotective effect in TBHP-induced hepatocyte injury partly by inhibiting Ca2+-calpain-mu-mediated mechanisms.

Alprostadil↗