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Biomedical subjects

Hiromitsu Saisho

Publications and source records attributed to Hiromitsu Saisho.

At least 91 records · Page 5Linked to original sources
PubMed2004

Different behaviors of microbubbles in the liver: time-related quantitative analysis of two ultrasound contrast agents, Levovist and Definity.

The differences in time-related changes of liver images were compared quantitatively between Levovist and Definity. A total of 40 rabbits were assigned to eight groups according to the timing of taking enhanced liver images at 1, 3, 5, 7, 9, 11, 13 and 15 min by intermittent harmonic imaging using Levovist or Definity (30 microL/kg) and another 40 rabbits for Definity (50 microL/kg). Intensity changes between before and after enhancement in the portal vein (I-PV) and liver parenchyma (I-LP) were analyzed. I-PV was greater than I-LP at the 1- and 3-min phases of enhancement and I-LP became greater than I-PV with Levovist after 5 min. However, I-PV was higher than I-LP in all phases with Definity. Different time-intensity curves of these two agents will indicate discrete behaviors of microbubble hemodynamics in the liver; Levovist becomes accumulated in the liver, whereas Definity acts as a blood pool contrast agent, without accumulation.

Animals↗
PubMed2004

Mitochondrial signal lacking manganese superoxide dismutase failed to prevent cell death by reoxygenation following hypoxia in a human pancreatic cancer cell line, KP4.

One of the major characteristics of tumor is the presence of a hypoxic cell population, which is caused by abnormal distribution of blood vessels. Manganese superoxide dismutase (MnSOD) is a nuclear-encoded mitochondrial enzyme, which scavenges superoxide generated from the electron-transport chain in mitochondria. We examined whether MnSOD protects against hypoxia/reoxygenation (H/R)-induced oxidative stress using a human pancreas carcinoma-originated cell line, KP4. We also examined whether MnSOD is necessarily present in mitochondria to have a function. Normal human MnSOD and MnSOD without a mitochondrial targeting signal were transfected to KP4 cells, and reactive oxygen species, nitric oxide, lipid peroxidation, and apoptosis were examined as a function of time in air following 1 day of hypoxia as a H/R model. Our results showed H/R caused no increase in nitric oxide, but resulted in increases in reactive oxygen species, 4-hydroxy-2-nonenal protein adducts, and apoptosis. Authentic MnSOD protected against these processes and cell death, but MnSOD lacking a mitochondrial targeting signal could not. These results suggest that only when MnSOD is located in mitochondria is it efficient in protecting against cellular injuries by H/R, and they also indicate that mitochondria are primary sites of H/R-induced cellular oxidative injuries.

Aldehydes↗
PubMed2004

Spontaneous rupture of pancreatic metastasis from renal cell carcinoma.

We report the case of a 53-year-old female who was admitted for sudden abdominal pain. Her right kidney was resected in 1993 due to renal cell carcinoma. Abdominal computed tomography performed in September 2002, while she was placed under observation, revealed a tumor 40 mm in size that extended from the head to the body of the pancreas. Abdominal ultrasonography on admission indicated retention of ascites, and the aspirated ascites was bloody. Based on this result, spontaneous rupture of a pancreatic tumor was strongly suspected. On abdominal contrast-enhanced computed tomography, multiple tumors were clearly visualized in the pancreas. Angiography revealed high-density tumor in the early arterial phase. The results of endocrinological tests were normal. Accordingly, the patient was diagnosed with multiple pancreatic metastases of renal cell carcinoma, and total pancreatectomy was performed. Histopathologically, the tumor resected was clear cell carcinoma and corresponded to the renal cell carcinoma resected in 1993. This is a rare case of pancreatic metastasis of renal cell carcinoma that resulted in spontaneous rupture 9 years after nephrectomy.

Angiography↗
PubMed2004

Diagnostic imaging for pancreatic cancer: computed tomography, magnetic resonance imaging, and positron emission tomography.

Computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) are sophisticated modalities typically used in the second-line diagnosis following routine clinical practice. Among them, CT is regarded as the standard imaging in diagnosing pancreatic cancer at present in Japan due to its popularity and reasonable reliability in wide-ranging diagnostic ability. However, even with multidetector row CT (MDCT), the demonstration of pancreatic cancer less than 1 cm in size remains nearly impossible. CT staging is considered accurate in one-half to two-thirds of patients, but limitations in the imaging of peripancreatic microinvasion and nodal or hepatic micrometastases still have a tendency to underestimate tumor extension. With recent advancement in imaging techniques, MRI has proven to be equal or superior to other imaging modalities in diagnosing pancreatic cancer. Most of all, it is expected that MRCP will become as effective an instrument as ultra-sonography (US) in the screening of pancreatic cancer. Functional imaging with PET using the glucose analog FDG can be used in the diagnosis of pancreatic cancer, but systemic or local disturbance of glucose metabolism may result in an incorrect diagnosis. The usefulness of PET is now considered in assessing tumor viability, monitoring tumor response to treatment, and detecting distant metastases.

Carcinoma↗
PubMed2004

Evaluation of blood flow in pancreatic ductal carcinoma using contrast-enhanced, wide-band Doppler ultrasonography: correlation with tumor characteristics and vascular endothelial growth factor.

BACKGROUND AND AIMS: Tumor vascularization has been attracting attention. However, there have been only a few reports on tumor vascularization in pancreatic ductal carcinoma, especially on vascularization depicted by imaging modalities. We investigated the relationship among wide-band Doppler signals, clinicopathological factors, and vascular endothelial growth factor (VEGF) expression. METHODS: Sixty-nine patients with pancreatic ductal carcinoma were investigated. The vascular signals from carcinoma lesions were assessed by contrast-enhanced, wide-band Doppler ultrasonography (dynamic flow). VEGF expression was quantitated by enzyme immunoassay for 28 patients. Depending on the intensity of the signals, the patients were classified into type A (definite vascular signal) or type B (almost no vascular signal). RESULTS: Type A patients and type B patients accounted for 65% and 35% of patients, respectively. According to multivariate analysis of vascular signal type and clinicopathological factors, liver metastasis occurred significantly more frequently in the type A group. VEGF expression was also significantly higher in the type A group than in the type B group. CONCLUSIONS: Dynamic flow has very high sensitivity for detecting the vascular signals from pancreatic ductal carcinoma. The quantity of vascular signals correlated with tumor characteristics and VEGF.

Carcinoma, Pancreatic Ductal↗
PubMed2004

Immunohistochemical localization of type IV collagen alpha chains in the basement membrane of the pancreatic duct in human normal pancreas and pancreatic diseases.

The type IV collagen (Col-IV) consists of 3 alpha chains. Six different alpha chains [alpha1(IV), alpha2(IV), alpha3(IV), alpha4(IV), alpha5(IV), and alpha6(IV)] have been identified, and their combination is considered to be organ specific. We investigated the immunohistochemical localization of alpha (IV) chains in the basement membrane (BM) of the pancreatic duct in human normal pancreas (NP) and pancreatic diseases. Fifty specimens [10 NP, 10 chronic pancreatitis (CP), 10 intraductal papillary mucinous tumor (IPMT), and 20 pancreatic adenocarcinoma (PAC)] were examined. Alpha 1(IV), alpha2(IV), alpha5(IV), and alpha6(IV) were linearly immunostained in NP, CP, and IPMT. In PAC, alpha(IV) and alpha2(IV) were immunostained, but alpha5(IV) and alpha6(IV) were not stained in 30% and 40% of the cases, respectively. In conclusion, immunohistochemically, the Col-IV of human normal pancreatic duct consisted of alpha1(IV), alpha2(IV), alpha5(IV), and alpha6(IV). alpha5(IV) and alpha6(IV) were frequently absent in PAC, and their absence might be related to the invasion of cancer cells.

Adenocarcinoma↗
PubMed2004

Distinguishing benign from malignant intraductal papillary mucinous tumors of the pancreas by imaging techniques.

OBJECTIVES: It is often difficult to differentiate benign from malignant intraductal papillary mucinous tumors (IPMTs). This study aimed to differentiate them using various imaging techniques. METHODS: Receiver operating characteristic curves were used to establish optimal cutoff values to differentiate benign from malignant tumors in 121 patients with histologically confirmed IPMTs. RESULTS: For branch duct type, accuracy for malignancy was highest using endoscopic ultrasonography (EUS) to measure the cyst diameter, and accuracy was 68.2% at a cutoff value of 33.9 mm. For main duct type, accuracy was highest, 71.1% at a cutoff value of 8.4 mm for main duct diameter, with magnetic resonance cholangiopancreatography. For all imaging techniques and findings, accuracy was highest using EUS, 76.4% at a cutoff value of 5.4 mm for height of protrusion. Each imaging technique had a positive predictive value of 80% if the cut off value for the height of the protruding lesion was met. CONCLUSIONS: Malignancy can be strongly suspected when the height of protrusion exceeds the respective cutoff values. EUS was most effective to differentiate benign IPMTs from malignant tumors by assessing the height of protrusion.

Adenocarcinoma, Mucinous↗
PubMed2004

Fatal chronic active Epstein-Barr virus infection mimicking autoimmune hepatitis.

We report a 22-year-old female who presented with pyrexia, pancytopenia and liver dysfunction. The patient showed mild liver dysfunction with low-grade fever and mild hepatosplenomegaly 6 years previously, and autoimmune hepatitis (AIH) was diagnosed based on the examination of the laboratory data and liver biopsy. On admission, both markers of Epstein-Barr virus (EBV) and in-situ hybridisation from a liver biopsy specimen indicated chronic active EBV infection (CAEBV). The patient was administered an immunosuppressive agent and antiviral drug added to steroid therapy, but ultimately died from liver failure and virus-associated haemophagocytosis 10 months after the definite diagnosis. Retrospective examination of the serum at the diagnosis of AIH revealed extremely high titres of antibody to EBV, and EBV-DNA was also detectable by polymerase chain reaction. These results suggest the possibility that the patient may already have suffered from CAEBV at the initial diagnosis. We presume that hepatic involvement of CAEBV should be considered as differential diagnosis in cases showing liver dysfunction with clinical and biochemical features observed in AIH.

Adult↗
PubMed2004

Cell growth inhibition and gene expression induced by the histone deacetylase inhibitor, trichostatin A, on human hepatoma cells.

OBJECTIVE: Histone deacetylase (HDAC) inhibitors have been reported to induce cell growth arrest, apoptosis and differentiation in tumor cells. The effect of the HDAC inhibitor, trichostatin A (TSA), on hepatoma cells, however, has not been well studied. In this study, we examined cell viability and gene expression profile in hepatoma cell lines treated with TSA. METHODS: To study cell growth inhibition and induction of apoptosis by TSA on human hepatoma cell lines including HuH7, Hep3B, HepG2, and PLC/PRF/5, cells were treated with TSA at various concentrations and analyzed by the 3-(4, 5-dimethyl-2-thiazolyl)-2H-tetrazolium bromide (MTT) and TUNEL assays, respectively. Changes in gene expression profile after exposure to TSA were assessed using a cDNA microarray consisting of 557 distinct cDNA of cancer-related genes. The levels of acetylated histones were examined by the chromatin immunoprecipitation (ChIP) assay using anti-acetylated histone H3 or H4 antibody. RESULTS: The MTT assay demonstrated that TSA showed cell growth inhibition not only in a concentration-dependent but also a time-dependent manner on all cell lines studied. The TUNEL assay also revealed the potential of TSA to induce apoptosis. The microarray analysis revealed that 8 genes including collagen type 1, alpha2 (COL1A2), insulin-like growth factor binding protein 2 (IGFBP2), integrin, alpha7 (ITGA7), basigin (BSG), quiescin Q6 (QSCN6), superoxide dismutase 3, extracellular (SOD3), nerve growth factor receptor (NGFR), and p53-induced protein (PIG11) exhibited substantial induction (ratio >2.0) after TSA treatment in multiple cell lines. ChIP assay, in general, showed a good correlation between the expression level of mRNA and levels of acetylated histones in these upregulated genes. CONCLUSIONS: This study showed cell growth inhibition and the gene expression profile in hepatoma cell lines exposed to TSA. The alteration in levels of acetylated histones was closely associated with expression of specific cancer-related genes in hepatoma cells.

Antineoplastic Agents↗
PubMed2004

High sustained virologic response rate after interferon monotherapy in Japanese hepatitis C patients with a low HCV RNA titer and/or HCV genotype 2. A prospective study.

OBJECTIVE: Hepatitis C virus (HCV) RNA titer and HCV genotype are considered to be major determinants of the outcome of interferon monotherapy. To clarify whether interferon monotherapy is really effective in patients with the appropriate viral parameters, we prospectively examined these parameters and treated the patients with interferon monotherapy. METHODS: Sixty-four patients with an HCV RNA titer <100 kIU/ml and/or HCV genotype 2 were enrolled in the study. Eighteen patients with an HCV RNA titer >100 kIU/ml and genotype 1 were also enrolled as controls. All patients were treated with 10 megaunits of interferon-alpha2b every day for 2 weeks and then 3 times a week for 24 weeks. RESULTS: Of the 64 patients with either HCV RNA <100 kIU/ml and/or genotype 2, seven dropped out from the study. Of the remaining 57 who completed the treatment, 48 (84%) showed a virologic sustained response. In contrast, only 4 of the 18 patients (22%) with HCV RNA >100 kIU/ml and genotype 1 were virologic sustained responders (p < 0.001). CONCLUSION: Our current study showed that the patients with HCV RNA <100 kIU/ml and/or HCV genotype 2 are good candidates for interferon monotherapy.

Antiviral Agents↗
PubMed2004

Expression of poly(ADP-ribose) polymerase in human hepatocellular carcinoma and analysis of biopsy specimens obtained under sonographic guidance.

Poly[adenosine diphosphate (ADP)-ribose] polymerase (PARP), which is mainly located in the nucleus, catalyzes poly-ADP-ribosylation, and is associated with a variety of biological events such as DNA repair, cell proliferation and malignant transformation. The aim of this study was, using biopsy samples obtained under sonographic guidance, to assess whether PARP expression is altered in human hepatocellular carcinoma (HCC), and also to analyze the correlation between the expression of PARP and the patients' clinicopathologic features. Tumor and non-tumor specimens were obtained from a total of 27 HCC patients by percutaneous biopsy under sonographic guidance. Using homogenates of these samples, the expression of PARP in HCC was evaluated by Western blotting and compared with the patients' clinicopathologic features. Western blot analysis, using a total of 29 HCC and 27 non-tumor specimens, revealed that the expression of PARP was significantly increased in HCC compared with the non-tumor portions (p<0.01), and was greater in moderately differentiated HCC than in well differentiated HCC (p<0.05). The expression of PARP in HCC was increased in cirrhotic patients and tended to be greater in less differentiated tumors.

Aged↗
PubMed2004

[Imaging of acute pancreatitis--the role of US, CT and MRI].

Imaging of the pancreas with US and CT plays a major role in the diagnosis and evaluations of patients with acute pancreatitis. In severe acute pancreatitis, dynamic CT is essential to assess the severity of the disease and evaluate the complications. MRI is comparable to CT in its capacity to provide precise information about the severity of acute pancreatitis. MRI has some advantages over CT in being free from ionizing radiation and lower toxity of gadolinium which is used for contrast medium intravenously. The disadvantages of MRI, however, include cost, longer exam duration, limited availability and the practical difficulties of scanning a patient with ICU equipment.

Acute Disease↗
PubMed2003

Hepatocyte growth factor activator inhibitor 2/placental bikunin (HAI-2/PB) gene is frequently hypermethylated in human hepatocellular carcinoma.

To identify methylation-mediated silencing of genes in hepatocellular carcinoma (HCC), we surveyed genes induced by treatment with 5-aza-2'-deoxycytidine (5-Aza-CdR) in six human hepatoma cell lines using cDNA microarray analysis and determined the methylation status of 5' CpG islands by bisulfite DNA sequencing or methylation-specific PCR. Fifty genes exhibited a >5-fold induction in response to treatment with 5-Aza-CdR in at least one of the hepatoma cell lines examined. Among these genes, the hepatocyte growth factor activator inhibitor 2/placental bikunin (HAI-2/PB) gene was maximally induced by 5-Aza-CdR in three of six cell lines studied (HLE, HuH7, and Hep3B). Bisulfite sequencing revealed that the 5' CpG island of this gene was densely methylated in HLE, HuH7, and Hep3B cells. After treatment with 5-Aza-CdR, re-expression and demethylation of HAI-2/PB gene were detected in these cells. These findings suggest that HAI-2/PB expression may be inappropriately repressed by promoter hypermethylation in HCC. Methylation-specific PCR analysis demonstrated that HAI-2/PB hypermethylation occurred in 21 of 26 HCC tumors (80.8%), whereas in the corresponding nontumorous liver tissues, it was found in 7 of 26 samples (26.9%). In addition, HAI-2/PB hypermethylation was not detected in any of the seven normal liver samples from individuals without HCC. Reverse transcription-PCR analysis demonstrated that promoter hypermethylation was associated with the reduced expression of the HAI-2/PB gene in HCC tumors. In conclusion, we have found that the HAI-2/PB gene is silenced by promoter hypermethylation in human hepatoma cells by means of cDNA microarray analysis after 5-Aza-CdR treatment, and that HAI-2/PB hypermethylation occurs frequently in primary HCC tumors.

Antimetabolites, Antineoplastic↗
PubMed2003

Induction of systemic immunity by expression of interleukin-23 in murine colon carcinoma cells.

Interleukin-23 (IL-23), a novel cytokine composed of a newly identified p19 molecule and the p40 subunit of IL-12, can stimulate the proliferation in vitro of memory T cells. We examined whether Colon 26 murine colon carcinoma cells that were retrovirally transduced with the p19-linked p40 gene (Colon 26/IL-23) could produce antitumor effects in inoculated mice. The growth of Colon 26/IL-23 tumors developed in immunocompetent mice was significantly retarded and the tumors disappeared thereafter. Spleen cells from the mice that received Colon 26/IL-23 cells produced significant amounts of interferon-gamma, when they were cultured with irradiated Colon 26 but not irrelevant cells. Depletion of CD8(+) T cells suppressed the production of interferon-gamma. The mice that had rejected Colon 26/IL-23 tumors were resistant to subsequent challenge of parent but not irrelevant tumor cells. Colon 26/IL-23 tumors were not rejected in nude mice but the growth was retarded compared to parent tumors. Treatment of nude mice with anti-asialo GM(1) antibody did not influence the growth of Colon 26/IL-23 tumors. These data suggest that expression of IL-23 in tumors produces T cell-dependent antitumor effects and induces systemic immunity.

Animals↗
PubMed2003

Gene expression profiling reveals the mechanism and pathophysiology of mouse liver regeneration.

Comprehensive analysis of the changes in gene expression during liver regeneration was carried out by using an in-house microarray composed of 2,304 distinct mouse liver cDNA clones. Mice were subjected to partial two-thirds hepatectomy, and changes in mRNA levels were monitored up to 48 h. Of the 2,304 genes analyzed, 496 genes showed expression levels measurable at all time points after the partial hepatectomy. 317 genes were up- or down-regulated 2-fold or more at least at one time point during liver regeneration and were classified into eight clusters based on their expression patterns. With a more stringent cut-off value of +/-2 S.D., 68 genes were listed and were classified into five clusters. In these two analyses with different clustering criteria, functionally categorized genes showed similar cluster distributions. Genes involved in protein synthesis and posttranslational processing were significantly enriched in the cluster characterized by rapid gene activation and subsequent persistence. This suggests the importance of modulating the efficiency of protein supply and/or altering the composition of protein population from the early phase of hepatocyte proliferation. Genes for two major liver functions, i.e. plasma protein secretion and intermediate metabolism were enriched in distinct clusters exhibiting the features of gradual gene activation and sustained repression, respectively. Therefore, these genes are differentially regulated during the regeneration, possibly leading to changes in the flow of amino acids and energy from enzyme proteins to plasma proteins in their synthesis. Thus, clustering analysis of expression patterns of functionally classified genes gave insights into mechanism and pathophysiology of liver regeneration.

Animals↗