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Hiromitsu Saisho

Publications and source records attributed to Hiromitsu Saisho.

At least 127 records · Page 7Linked to original sources
PubMed2003

Chronic graft-versus-host disease complicated by acute hepatitis B.

We observed a 45-year-old man with acute hepatitis B while receiving treatment of chronic graft-versus-host disease (GVHD) of the liver. When he developed a sudden elevation of serum aminotransferases 17 months after bone marrow transplantation, he was under immunosuppressive therapy consisting of cyclosporin A against chronic GVHD of the liver. Serologic tests for hepatitis B virus (HBV) showed no reactivation but de novo acute infection. The serum levels of aminotransferases after elevation of biliary tract enzymes increased mildly. However, icterus was not observed in his sequential course. A liver biopsy specimen revealed mild acute liver injury accompanied by slight degeneration of bile ducts. It is presumed that owing to immunosuppressive therapy, his liver dysfunction was relatively mild, and the hepatitis became quiescent without becoming serious. On the other hand, the serum of the patient remained hepatitis B surface antigen positive for more than 1 year after the onset of the hepatitis, which suggested chronicity of HBV infection.

Acute Disease↗
PubMed2003

Analysis of T cell receptor variable regions and complementarity determining region 3 of infiltrating T lymphocytes in the liver of patients with chronic type B hepatitis.

OBJECTIVES: T cell receptor (TCR) variable regions and complementarity determining regions 3 (CDR3) of infiltrating T cells in the livers of patients with chronic hepatitis B were examined in detail. METHODS: TCR usage was examined by the inverse polymerase chain reaction in 2 hepatitis B e antigen-positive patients, one at an early stage and the other at an advanced stage. RESULTS: In 61 productively rearranged clones bearing TCRalpha genes in the liver of the patient with early stage chronic hepatitis B, the Valpha 7.2 gene segment was most frequently used (16.4%), while the other Valpha gene segments were used less frequently. All but one of the clones with the Valpha7.2 gene were joined with the Jalpha33 gene, and the CDR3 regions of these clones were the same length and similar in amino acid sequence. In contrast, in 68 productively rearranged clones from the liver of the patient with advanced stage disease, all Valpha gene segments were used less frequently, and combinations of the Valpha and Jalpha gene segments varied. CONCLUSIONS: Our data suggest a relatively restricted usage of TCR in the liver in early stage chronic hepatitis B.

Adult↗
PubMed2003

Metal contents in the liver of patients with chronic liver disease caused by hepatitis C virus. Reference to hepatocellular carcinoma.

BACKGROUND/AIMS: The aim of this study was to investigate the relationship between trace metals and the prevalence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis or hepatic cirrhosis caused by hepatitis C virus (HCV). METHODS: We measured the contents of copper, iron, and zinc in HCC tissue (n = 112), dysplastic nodules (n = 7), and liver parenchyma in patients with (n = 112) and without (n = 12; 7 with grade F3 fibrosis, 5 with grade F4 fibrosis) HCC. Metals were quantified in thin-needle biopsy specimens using the particle-induced X-ray emission method (PIXE). RESULTS: Copper level in liver parenchyma was higher in patients with HCC than in those without HCC (p < 0.01), while there was no such difference in hepatic iron. In patients with grade F4 fibrosis, copper content in the liver parenchyma was higher in the presence of HCC than in its absence (p < 0.05). Multiple regression analysis showed that the only factor significantly associated with the coexistence of HCC in HCV-positive patients with chronic liver disease was the copper level in the liver parenchyma. CONCLUSIONS: Hepatic copper overload may contribute to the development of HCC in HCV-positive patients with chronic hepatitis or cirrhosis.

Adult↗
PubMed2003

Extra-low acoustic power harmonic images of the liver with perflutren: novel imaging for real-time observation of liver perfusion.

OBJECTIVE: The features of images below the extra-low mechanical index level were studied to elucidate a suitable mechanical index level for observing real-time and continuous harmonic images of rabbit livers with VX-2 tumors with the use of perflutren. METHODS: Eight New Zealand White rabbits, 2 with healthy livers and 6 with VX-2 tumors, were examined by harmonic imaging (1.85 and 3.7 MHz) at a frame rate of 17 Hz under various mechanical index levels. RESULTS: Real-time enhanced images of the liver were observed continuously in all rabbits. Vascular images were more clearly visualized at the low mechanical index level (mechanical index, 0.18) than at any other level. However, predominant enhanced images of the whole liver were observed only at the extra-low mechanical index level (mechanical index, 0.06). In VX-2 tumors, tumor vessels were shown more clearly at a low acoustic power level than at an extra-low level. The histologically proved area of viable tumor was enhanced as a stain in the tumor nodule at an extra-low mechanical index level. CONCLUSIONS: Harmonic imaging under extra-low mechanical index levels with perflutren could provide real-time and continuous enhanced images of the liver, which would contribute to improvement of the diagnostic ability of contrast-enhanced sonography in liver diseases.

Animals↗
PubMed2003

Stage-specific expression of Clast6/E3/LAPTM5 during B cell differentiation: elevated expression in human B lymphomas.

We have identified a CD40-regulated gene, Clast6/E3/LAPTM5, by subtraction of cDNAs derived from resting and CD40 ligand-treated B cells. Clast6/E3/LAPTM5 is abundantly expressed in resting mature B cells but is rapidly and transiently repressed by treatment with CD40 ligand, a T helper signal that induces B cell activation. Using a fluorescence activated cell sorter, we have purified B-lineage cells into distinct populations based on their differential expression of cell surface markers. Clast6/E3/LAPTM5 was found to be highly expressed in progenitor and precursor B cells, downregulated in late pre-B and immature B cells, and upregulated again in mature B and the germinal center B cells. Interestingly, Clast6/E3/LAPTM5 was expressed at high levels in malignant B lymphomas. These results reveal stage-specific expression of Clast6/E3/LAPTM5 during B cell differentiation and implicates its possible involvement in B cell malignancies.

B-Lymphocytes↗
PubMed2003

Survival regulation in pancreatic cancer cells by c-Jun.

Over 90% of human pancreatic cancers harbor an activating point mutation in the K-ras gene at codon 12. However, it is not clear whether all downstream K-ras are activated and which downstream contributes to the cell survival and proliferation of pancreatic cancer cells. MEK kinase 1 (MEKK1)-c-Jun N-terminal kinase (JNK)-c-Jun pathway has an important role in cell proliferation, survival and apoptosis in various cells. We previously demonstrated that the dominant negative form of MEKK1 (DN-MEKK) inhibits the survival of human pancreatic cancer cell lines. In this study we investigated whether JNK-c-Jun, the downstream pathway of DN-MEKK, affects the survival of human pancreatic cancer cell lines. Colony formation assays indicated that c-Jun failed to inhibit the survival of pancreatic cancer cells, whereas c-Jun remarkably inhibited the cell survival of non-pancreatic cancer cells. Reporter gene assays using Gal4-c-Jun and gel retardation assays indicated that c-Jun functions were activated in growing pancreatic cancer cells. These results revealed that c-Jun activation does not prevent the cell survival of pancreatic cancer cells in contrast to non-pancreatic cancer cells. It appears that MEKK1-JNK-c-Jun pathway fails to act as a negative regulator for the cell survival of pancreatic cancer cells. Greater understanding of these mechanisms may be helpful in the treatment of pancreatic cancer.

Apoptosis↗
PubMed2003

[A case of membranous nephropathy with ANCA-associated necrotizing glomerulonephritis during oral administration of PTU for Graves' disease].

We experienced a coincidental case of two types of glomerulopathy associated with Graves' disease. A 64-year-old man, who had been treated with propylthiouracil(PTU) for Graves' disease for 15 years, was admitted to our hospital for macroscopic hematuria and rapidly progressive deterioration of renal function. Although his thyroid function had been within the normal range during treatment, the level of thyrotropin receptor antibody(TRAb) gradually increased from a year before admission. Serological tests revealed that he was positive for myeloperoxidase-antineutrophil cytoplasmic antibody(MPO-ANCA). The renal biopsy specimen showed necrotizing and crescentic glomerulonephritis(GN) superimposed on membranous nephropathy(MN). This is a rare case of MN complicated with ANCA associated crescentic GN in a Graves' disease patient. Association of these two renal alterations was not clearly defined. MN involved with Graves' disease also has been rarely reported. Some reports demonstrated deposition of thyroglobulin and other thyroid related antigens in the glomeruli. In the present case, long-term impairment of Graves' disease and elevation of TRAb might have been responsible for the formation and deposition of thyroid-associated immune complex in the glomeruli. As for crescentic GN, PTU might have induced ANCA-associated GN independently of MN. This case is instructive for considering the relation between Graves' disease and renal injury.

Administration, Oral↗
PubMed2002

Endoscopic internal biliary drainage in a child with malignant obstructive jaundice caused by neuroblastoma.

We describe a 13-year-old girl who underwent insertion of a Flexima biliary stent for obstructive jaundice due to compression of the extrahepatic bile duct by an enlarged lymph node secondary to neuroblastoma. This novel endoscopic internal biliary drainage procedure was safe and effective even for a child, and improved her quality of life. We further review other treatment options available for malignant obstructive jaundice in children.

Bile Ducts, Intrahepatic↗
PubMed2002

Downregulation of bcl-xL is relevant to UV-induced apoptosis in fibroblasts.

Exposure to ultraviolet light (UV) induces apoptosis in mammalian cells. The caspase group of proteases is required for the apoptosis. This pathway is initiated by a release of cytochrome c from the mitochondria into the cytosol. Several Bcl-2 family proteins can regulate the release of cytochrome c by stabilizing the mitochondrial membrane. Here we show that expression of the endogenous bcl-xL was strongly downregulated in NIH3T3 cells within 2 h after UV-C irradiation, and that of bax was upregulated from 8 h after irradiation. Apoptosis was induced in more than 50% of the NIH3T3 cells 48 h after irradiation. Constitutive overexpression of bcl-xL in NIH3T3 cells protected the UV-induced apoptosis by preventing the loss of mitochondrial membrane potential and the activation of caspase 9. These results suggest that downregulation of Bcl-xL is relevant to UV-induced apoptosis of fibroblasts.

3T3 Cells↗
PubMed2002

Dominant negative MEKK1 inhibits survival of pancreatic cancer cells.

Human pancreatic cancers harbor mutations in the K-ras gene, and these mutations convert the gene oncogenic and constitutively active forms. However, in pancreatic cancer cells little is known about the activation of the downstream pathways of Ras, MEK-ERK and MEKK1-JNK, and their roles in cell survival and proliferation. An analysis of nine pancreatic cancer tissues revealed JNK activation in all tumor samples and ERK activation in three tumor samples. Colony formation assays by transfection of dominant negative mutants of Ras, ERK or MEKK1 into pancreatic cancer cell lines (BxPC-3, PANC-1, MIAPaCa-2 and AsPC-1) and an amnion-derived cell line (FL) revealed that DN-MEKK strongly inhibits the survival of colonies in pancreatic cancer cells, but not in FL cells. In vitro kinase assays and luciferase assays using the Gal4c-Jun system revealed that in pancreatic cancer cells DN-MEKK fails to inhibit JNK activation. In PANC-1 cells, c-Jun was found to be a major component of protein component binding to AP-1 site and CRE, but not in FL cells. The inhibitory effect of DN-MEKK in PANC-1 cells was thought to be the result of the inhibition of c-Jun DNA-binding. The difference of suppression in pancreatic cancer cells and non-pancreatic cancer cells suggested that the MEKK1 pathway mainly contributes to cell survival in pancreatic cancer cells and may provide an advantage for the gene therapy of pancreatic cancers using DN-MEKK expression vectors.

Adenocarcinoma↗
PubMed2002

Clast5/Stra13 is a negative regulator of B lymphocyte activation.

CD40 is a member of the tumor necrosis factor receptor family and mediates a variety of functions of B cells, including B cell survival, proliferation, immunoglobulin gene class switching, memory B cell formation, and regulation of Fas-mediated apoptosis. To begin to elucidate the molecular mechanism governing such diverse functions of CD40, we have isolated a gene from mouse splenic B cells, termed Clast5, whose expression is strongly repressed during B cell activation. Clast5 is identical with Stra13, a recently identified member of the basic helix-loop-helix family of transcription factors. Clast5/Stra13 is highly expressed in unstimulated, resting B cells and is rapidly downregulated by a variety of stimuli that activate B cells, including CD40 ligand, anti-IgM antibodies, lipopolysaccharides and interleukin-4. Forced expression of Clast5/Stra13 in B cells delayed the cell cycle progression into S phase and strongly suppressed Fas-mediated apoptosis. Moreover, Clast5/Stra13 inhibited the colony formation in fibroblasts. Our results suggest that Clast5/Stra13 functions as a negative regulator of B cell activation by inhibiting cell cycle progression and cell growth.

3T3 Cells↗
PubMed2002

Immunohistochemical analysis and in situ hybridization of cyclooxygenase-2 expression in intraductal papillary-mucinous tumors of the pancreas.

BACKGROUND: The objective of this study was to investigate COX-2 expression in intraductal papillary-mucinous tumor of the pancreas (IPMT) using immunohistochemical staining (IH) and in situ hybridization (ISH). METHODS: Immunohistochemical staining of COX-2 was performed using samples from 42 patients with IPMT (hyperplasia, 10; adenoma, 13; noninvasive adenocarcinoma, 13; invasive adenocarcinoma, 6) and from 10 patients with ductal pancreatic adenocarcinoma, 10 with chronic pancreatitis, and 6 normal pancreatic tissues as controls. Also, COX-2 was determined in five patients with IPMT noninvasive adenocarcinoma, in whom all histologic types, hyperplasia, adenoma, and adenocarcinoma were observed in the same excised specimens. Furthermore, IH of proliferating cell nuclear antigen (PCNA) was performed, and the labeling index (LI) was calculated to investigate the correlation with COX-2. To confirm COX-2 mRNA, the authors performed ISH in 20 IPMT patients. RESULTS: COX-2 was positive in 0%, 0%, and 10% of pancreatic duct epithelial cells from normal pancreatic tissue, chronic pancreatitis, and IPMT hyperplasia, respectively. Whereas it was positive in 69%, 77%, 67%, and 80% of IPMT adenoma, IPMT noninvasive adenocarcinoma, IPMT invasive adenocarcinoma, and ductal pancreatic adenocarcinoma, respectively, showing significant differences between IPMT hyperplasia and IPMT adenoma or IPMT adenocarcinoma (noninvasive and invasive adenocarcinoma). In the same patient, COX-2 was negative in the hyperplasia region but positive in adenoma and adenocarcinoma regions, showing results reflecting the progression of the disease. In the COX-2 negative group, PCNA-LI was 19.2 +/- 17.9%, and 33.5 +/- 15.7% in the positive group, a significant difference. On ISH, COX-2 mRNA was expressed in three of four and seven of eight COX-2 positive patients with IPMT adenoma and adenocarcinoma, respectively. CONCLUSIONS: COX-2 was highly expressed in adenoma and adenocarcinoma in IPMT, showing a relation to the histologic grade of IPMT.

Adenocarcinoma↗
PubMed2002

Evaluation of the clinical usefulness of COBAS AMPLICOR HCV MONITOR assay (ver2.0): Comparison with AMPLICOR HCV MONITOR assay (ver1.0) and HCV core protein level.

The quantitation of serum levels of hepatitis C virus (HCV) RNA in chronic hepatitis C has been regarded as one of the most important indicators for the outcome of interferon (IFN) therapy. The AMPLICOR HCV MONITOR version 1.0 (AMPLICOR v1.0) assay is widely used for the evaluation of the HCV level. A new generation assay called the COBAS AMPLICOR HCV MONITOR version 2.0 (COBAS v2.0) assay, which is semiautomated and modified to amplify all genotypes equally, has been developed. The aim of this study was to evaluate the clinical relevance of the COBAS v2.0 assay in comparison with the AMPLICOR v1.0 assay and HCV core protein assay in patients with chronic hepatitis C before IFN therapy. HCV RNA was detectable in 230 cases (97.5%) and undetectable in 6 cases (2.5%) by the COBAS v2.0 assay. The RNA levels measured by the AMPLICOR v1.0 assay correlated significantly with those measured by the COBAS v2.0 assay, and the sensitivity of the new version 2.0 assay was better than that of version 1.0, especially in serotype 2. In relation to the outcome of IFN therapy, HCV RNA levels from virologically sustained responders by the AMPLICOR v1.0 assay were 82.3 +/- 22.9 kcopies/ml in serotype 1 and 36.9 +/- 13.4 kcopies/ml in serotype 2, and those from virologically nonsustained responders were 525.2 +/- 48.6 kcopies/ml in serotype 1 and 76.7 +/- 19.5 kcopies/ml in serotype 2. The rates of sustained response to <100 kcopies/ml were 34/63 (54.0%) in serotype 1 and 24/48 (50.0%) in serotype 2. A statistically significant virological response was seen in serotype 1 (P < 0.0001), but not in serotype 2. In contrast, the levels in virologically sustained responders by the COBAS v2.0 assay were 88.2 +/- 20.5 KIU/ml in serotype 1 and 136.8 +/- 40.1 KIU/ml in serotype 2, and those in virologically nonsustained responders were 608.8 +/- 48.4 KIU/ml in serotype 1 and 328.3 +/- 62.8 KIU/ml in serotype 2. The rates of sustained response to <100 KIU/ml were 33/60 (55.0%) in serotype 1 and 21/35 (60.0%) in serotype 2. Statistical significance in virological response was seen in both serotype 1 (P < 0.0001) and serotype 2 (P < 0.05). Although the sensitivity of the HCV core protein assay was lower than that with the COBAS v2.0 assay, the HCV core protein levels also correlated well with the results of the COBAS v2.0 assay. The HCV core protein levels of virologically sustained responders were 37.6 +/- 12.0 pg/ml in serotype 1, 81.3 +/- 37.0 pg/ml in serotype 2, and those of virologically nonsustained responders were 289.9 +/- 23.5 pg/ml in serotype 1, 191.4 +/- 32.1 pg/ml in serotype 2. This assay could predict the outcome of IFN therapy in both serotype 1 (P < 0.0001) and serotype 2 (P < 0.05). Thus, both the COBAS v2.0 assay and the HCV core protein assay showed that the viral load was an indicator of virologically sustained response in serotype 2 and in serotype 1.

Adolescent↗
PubMed2002

Role of RANTES in the development of autoimmune tissue injuries in MRL-Fas lpr mice.

MRL-Fas lpr mice spontaneously develop a severe autoimmune disease closely resembling human SLE. To investigate the possible role of RANTES in autoimmune tissue injuries, we have constructed RANTES-deficient MRL-Fas lpr mice by gene targeting. In the RANTES-deficient mice, axillary lymph nodes were significantly reduced in size compared with those of RANTES-intact mice. Flow cytometric analysis revealed that double-negative (DN) T cells were significantly reduced. Image analyzer showed that cell-infiltrated areas in peribronchial lesions were decreased in the lung of RANTES-deficient MRL-Fas lpr mice. Furthermore, we detected continuous expression of RANTES mRNA in the lung of MRL-Fas lpr mice. In contrast, the degree of histological renal injuries and survival rate was similar in both genotypes. We speculate that RANTES is involved in the development of peribronchial pulmonary lesions in MRL-Fas lpr mice. Further studies using RANTES-deficient mice might contribute to the elucidation of the role of RANTES in autoimmune tissue injuries.

Animals↗
PubMed2002

Peroral cholangioscopic treatment of hepatolithiasis: Long-term results.

BACKGROUND: Peroral cholangioscopic lithotomy is an effective treatment for extrahepatic bile duct stones. However, an evaluation of the usefulness and long-term results of peroral cholangioscopic lithotomy for hepatolithiasis has not been reported. The aim of this study was to evaluate the usefulness and long-term results of peroral cholangioscopic lithotomy for hepatolithiasis. METHODS: From August 1987 to July 1998, 36 consecutive patients underwent peroral cholangioscopic lithotomy for hepatolithiasis; 34 were followed for a mean of 93 months (range, 14 to 164 months). RESULTS: The rate of complete stone removal was 64%; the morbidity rate was 2.8%. The recurrence rate for patients in whom stones were completely removed was 21.7%. Two patients (5.9%) had cholangiocarcinoma develop during follow-up. CONCLUSION: Although incomplete stone removal and recurrence are common, peroral cholangioscopic lithotomy is a sufficiently safe and effective method for the treatment of hepatolithiasis.

Adult↗
PubMed2002

Diagnosis of gallstone composition in magnetic resonance imaging: in vitro analysis.

OBJECTIVE: To elucidate the cause of the signal intensity of gallstones on magnetic resonance (MR) images and to determine whether MR imaging would enable the prediction of the composition of gallstones. MATERIALS AND METHODS: 50 gallstones removed by cholecystectomy from 50 patients were used for in vitro study. All 50 gallstones were examined by MR imaging using a body phantom. After imaging, all gallstones were cut into two pieces, and the MR appearances were compared with their cross-sections. Chemical analysis was subsequently performed on 32 gallstones. RESULTS: On T2-weighted (T2W) images, 24 of 50 gallstones showed high signal intensities only in their center. These central high intensities seen on T2W images corresponded to the clefts filled with fluid within gallstones. In 45 of 50 gallstones there were high signal intensity areas in central and/or peripheral regions on T1-weighted (T1W) images. On T1W images, not only the clefts within gallstones but also other regions were seen as high intensity, and these regions had a brown to black color, coarse structure, and contained much copper. CONCLUSION: MR imaging can visualize the structures and compositions of gallstones in detail.

Calcium Carbonate↗