Biomedical subjects

Yoshitake Hayashi

Publications and source records attributed to Yoshitake Hayashi.

At least 37 records · Page 2Linked to original sources

PubMed2005

Primary sclerosing cholangitis and hepatitis C virus infection.

Two cases of primary sclerosing cholangitis with hepatic C virus infection in a 62-year-old man and a 60-year-old woman are presented. The infection in the man was eradicated with interferon therapy in 1992. Seven years thereafter, endoscopic retrograde cholangiography revealed a diffuse 2.5-cm-long stenotic lesion in the common bile duct which was consequently resected. Histological examination of the resected specimen revealed proliferation of epithelial cells, plasma cell infiltration, and fibrosis in the submucosal layer of the common bile duct. The human leukocyte antigen DR loci were 2 and 9. In the woman, a 6-month course of interferon therapy in 1992 failed to eradicate the infection. Cholangiography in 1999 revealed multiple narrowings and dilatations of intra- and extrahepatic bile ducts. Ultrasound guided biopsy of the liver in 1992 had revealed onionskin lesions around the bile duct epithelium in the portal tract. The human leukocyte antigen DR locus was 2. From these findings, the 2 cases were diagnosed as primary sclerosing cholangitis. Further studies may provide insights into the relation between the pathogenesis of the disease and the infection.

Bile Ducts↗

PubMed2005

Long-term follow-up of Japanese patients with chronic hepatitis B treated with interferon-alpha.

The long-term usefulness of interferon-alpha (IFN-alpha) in chronic hepatitis B remains controversial. To investigate the long-term efficacy of IFN-alpha therapy in chronic hepatitis B, 62 Japanese patients, including 27 patients treated with IFN-alpha (IFN group) and 35 patients without antiviral therapy matched by age and sex as controls (control group), were followed up for 2-14 years. At entry, the serum alanine aminotransferase (ALT) level in the IFN group was significantly higher than that in the control group (238.6+/-250.1 vs. 142.3+/-152.1 IU/l, P < 0.05). The prevalence of genotype C was 89%, with no difference between the two groups (93 vs. 86%). There was no significant difference in the presence of the precore mutation or the dual core promoter mutations between the IFN and control groups (37 vs. 46%, 74 vs. 66%). After long-term follow-up, the rate of sustained HBeAg seroconversion was comparable in the two groups (33 vs. 31%). Normalization of serum ALT level was seen in 44% of the IFN group and 51% of the control group, with no difference. There was also no difference in the percentage of cases with loss of serum HBV-DNA by PCR assay between the two groups (33 vs. 29%). During follow-up, two patients of the control group and three patients of the IFN group developed cirrhosis, and one of the IFN- treated patients progressed to hepatocellular carcinoma. The results of this long-term follow-up study showed that no benefit of IFN-alpha treatment was detectable during long-term follow-up in Japanese patients with chronic hepatitis B.

Adult↗

PubMed2005

How to help Acehnese helping themselves?--a note after a visit with Kobe University medical team.

On December 26, Aceh Province in Indonesia was hit by the worst earthquake and tsunami. A medical team from Kobe University Graduate School of Medicine visited two of the affected areas on the eastern coast of Aceh: Sigli and Lhokseumawe. This article provides a simple description of experience and assessment derived from the visit. The disaster has left Indonesia with complex problems, which will take a long time to overcome. A continuity of the aid and assistance from various resources is crucial to help Indonesia rebuilt the affected areas. These continuous efforts will provide great contribution for Acehnese people to recover and rebuild their life after tsunami.

Disasters↗

PubMed2004

Expression and localization of ecto-nucleotide pyrophosphatase/phosphodiesterase I-1 (E-NPP1/PC-1) and -3 (E-NPP3/CD203c/PD-Ibeta/B10/gp130(RB13-6)) in inflammatory and neoplastic bile duct diseases.

Ecto-nucleotide pyrophosphatase/phosphodiesterase-I enzyme (E-NPP) consists of three closely related molecules: E-NPP1, E-NPP2 and E-NPP3. We investigated the expression and localization of E-NPP1 and -3 in human inflammatory and neoplastic bile duct diseases. Immunohistochemically E-NPP1 was located on the apical cytoplasmic side of cancer cells, whereas E-NPP3 was located in the apical plasma membrane. Western blot analysis revealed that the expression of E-NPP3, but not E-NPP1, was higher in tumor tissues than in surrounding tissues and the specific form of the E-NPP3 protein was readily detected in the sera of bile duct carcinoma (BDC) patients. Furthermore, it was confirmed that E-NPP3 was associated with migration ability by using of NIH3T3 cells that stably transfected with E-NPP3 cDNA. These results suggest that E-NPP3 is involved in the infiltration of neoplastic BDC and is possible to be a tumor marker.

Animals↗

PubMed2004

An aluminum influence on root circumnutation in dark revealed by a new super-HARP (high-gain avalanche rushing amorphous photoconductor) camera.

The circumnutation of a rice root under dark conditions was observed using a highly sensitive camera, a new super-HARP camera. A rice root showed regular rhythmic movement with fixed angle. When treated with Al (5 microM AlCl3), the rotation angle of the root tip was drastically decreased and then the movement was resumed again, whereas the root elongation rate was constant. With the increase of Al concentration, the cycle-fading period became shorter. This is the first report to show that an Al treatment ceased the rotation movement of the root but not elongation.

Aluminum↗

PubMed2004

Apoptotic pathway related to oval cell proliferation.

BACKGROUND AND AIM: Oval cells, liver stem cell-derived cells, are generated from the liver periportal region and spread into the parenchyma by an autocrine signaling pathway. The mechanism behind how oval cells take their place among packed silent hepatocytes, however, is not well understood. We hypothesized that apoptosis involves a decrease in hepatocytes surrounding oval cells. METHODS: Male Fisher rats were treated using the AAF/PH protocol to induce oval cells in the liver. Apoptosis was assessed by measuring the activity of caspase-3, -8 and -9, and apoptosis-related molecules such as caspase-3, Fas, Fas-L and Bax were also assessed by immunohistochemical analysis and reverse transcriptase-polymerase chain reaction (RT-PCR). Apoptosis was confirmed by TUNEL staining. Regarding antiapoptotic factors, nuclear factor-kappaB (NF-kappaB) DNA binding activity and proliferating cell nuclear antigen (PCNA) expression were examined. RESULTS: NF-kappaB elevated at the early stage of oval cell proliferation. Conversely, caspase activity increased after NF-kappaB elevation. The mRNA of caspase-3, Fas, Fas-L and Bax was induced during and after AAF/PH treatment. Immunohistochemically, oval cells lacked the expression of these proteins, whereas the hepatocytes, particularly those surrounding oval cells, expressed strongly. CONCLUSIONS: The present study suggests that the apoptosis in hepatocytes through both extrinsic and intrinsic pathways mediates oval cell proliferation.

Animals↗

PubMed2004

Early response to interferon alpha treatment and long-term clinical outcome in Japanese patients with chronic HBV genotype C infection.

Genotype C of hepatitis B virus (HBV) has been shown to be associated with a poor clinical outcome and less favorable response to interferon (IFN) alpha therapy compared to genotype B. We evaluated the response to IFN alpha therapy and long-term clinical outcome in Japanese patients with chronic active HBV genotype C infection. Thirty Japanese patients with chronic active hepatitis who received natural IFN alpha therapy were followed for 2-12 years (mean 5.9 years). Twenty-four patients were treated short-term (daily for 4 weeks at a mean total dosage of 174 million units) and 6 patients were treated long-term (total of 26 weeks at a mean total dosage of 687 million units). Twelve of 30 (40%) patients had an antiviral response at 6 months after therapy. Clinical data before treatment in both responders and non-responders were comparable. Although not significant, responders tended to have younger age, a higher serum transaminase level, a lower frequency of precore mutation (G1896A) (67% vs. 92%) and a higher frequency of core promoter mutation (A1762T/G1764A) (89% vs. 58%) than non-responders. The patients treated long-term responded significantly better than those treated short-term (83% vs. 29%, P=0.026). Up to 12 years after therapy, a higher percentage of responders than non-responders had sustained clearance of HBeAg with seroconversion and normalization of transaminase concentration at the followed end point (83% vs. 17%, P<0.001). Two non-responder patients had cirrhosis after long-term follow-up. One non-responder patient died of hepatocellular carcinoma 8 years after IFN therapy; except in this patient there was no development of decompensated cirrhosis. Early responsiveness to IFN alpha therapy in Japanese patients with chronic active HBV genotype C infection improves the long-term clinical outcome.

Adult↗

PubMed2003

IFN-alpha prevents the growth of pre-neoplastic lesions and inhibits the development of hepatocellular carcinoma in the rat.

Interferon (IFN)-alpha treatment is a common therapy for chronic viral hepatitis and contributes to preventing hepatocarcinogenesis. However, it is not clear whether IFN-alpha directly inhibits the clonal expansion of pre-neoplastic hepatocytes. To clarify the mechanism by which IFN-alpha prevents hepatocarcinogenesis, we examined the effect of IFN-alpha in a chemically induced hepatocarcinogenesis model initiated by diethylnitrosamine (DEN) and promoted by 2-acetylaminofluorene (2-AAF) and partial hepatectomy, in which hepatocellular carcinoma (HCC) arises through pre-neoplastic foci without inflammation or fibrosis. The protocols of IFN-alpha administration were started simultaneously with chemical initiation and lasted for either 4 or 40 weeks. The pre-neoplastic foci and neoplastic HCC were evaluated at 4 or 40 weeks after chemical initiation, respectively. The effects of IFN-alpha were assessed by the expression of tumor-related genes and cell cycle-related genes in the pre-neoplastic foci, using immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). As a result of IFN-alpha treatment, the numbers and average volume of pre-neoplastic foci were reduced. The proliferating cell nuclear antigen index and the expression of G(1) cyclins were also reduced in the pre-neoplastic foci in the IFN-treated group. The expression of p21, which is an inhibitor of cyclin-kinase complexes was higher in the foci of the IFN-treated group, while p53 expression was not altered in this group, compared with the control group. IFN-alpha also suppressed the tumor development at 40 weeks after initiation. And in the long-term IFN-alpha-treated group, both the tumor numbers and average tumor size were markedly more reduced than those in the short-term-treated group. Therefore, it was demonstrated that longer treatment with IFN-alpha was more effective, compared with shorter treatment. In conclusion, it was shown that IFN-alpha directly prevented and delayed hepatocarcinogenesis through the suppression of pre-neoplastic cell proliferation and that it may partially depend on p21 induction through a p53-independent pathway.

Animals↗

PubMed2003

Oxidative stress in the pathogenesis of thoracic aortic aneurysm: protective role of statin and angiotensin II type 1 receptor blocker.

OBJECTIVE: The pathogenesis of thoracic aortic aneurysms (TAA) is still unclear. A recent investigation indicated that angiotensin II, a potent activator of NADH/NADPH oxidase, plays an important role in aneurysmal formation. We investigated the potential role of p22phox-based NADH/NADPH oxidase in the pathogenesis of TAA. METHODS: Human thoracic aneurysmal (n=40) and non-aneurysmal (control, n=39) aortic sections were examined, and the localization of p22phox, an essential component of the oxidase, and its expressional differences were investigated by immunohistochemistry and Western blot. In situ reactive oxygen species (ROS) generation was examined by the dihydroethidium method, and the impact of medical treatment on p22phox expression was investigated by multiple regression analysis. RESULTS: In situ production of ROS and the expression of p22phox increased markedly in TAA throughout the wall, and Western blot confirmed the enhanced expression of p22phox. The expression was more intense in the regions where monocytes/macrophages accumulated. In these inflammatory regions, numerous chymase-positive mast cells and angiotensin converting enzyme-positive macrophages were present. Their localization closely overlapped the in situ activity of matrix metalloproteinase and the expression of p22phox. Multiple regression analysis revealed that medical treatment with statin and angiotensin II type 1 receptor blocker (ARB) suppressed p22phox expression in TAA. CONCLUSION: Our findings indicate the role of p22phox-based NADH/NADPH oxidase and the local renin-angiotensin system in the pathogenesis of TAA. Statin and ARB might have inhibitory effects on the formation of aneurysms via the suppression of NADH/NADPH oxidase.

Aged↗

PubMed2003

Downregulation of stomach cancer-associated protein tyrosine phosphatase-1 (SAP-1) in advanced human hepatocellular carcinoma.

SAP-1 (stomach cancer-associated protein tyrosine phosphatase-1) is a transmembrane-type protein tyrosine phosphatase that has been implicated as a negative regulator of integrin-mediated signaling. The potential role of this enzyme in hepatocarcinogenesis has now been investigated by examining its expression in 32 surgically excised human hepatocellular carcinoma (HCC) specimens. Both immunohistochemical and immunoblot analyses revealed that normal liver tissue, as well as tissue affected by chronic hepatitis or cirrhosis, contained substantial amounts of SAP-1. The expression level of SAP-1 in 75% of well-differentiated HCCs was similar to or higher than that observed in the surrounding noncancerous tissue. In contrast, the abundance of SAP-1 in 85.7% of moderately differentiated HCCs and in all poorly differentiated HCCs was greatly reduced compared with that in the adjacent tissue. Indeed, SAP-1 was almost undetectable in 83.3% of poorly differentiated HCCs. Furthermore, expression of recombinant SAP-1 in two highly motile human HCC cell lines resulted in a change in morphology and a marked reduction in both migratory activity and growth rate. In conclusion, these results indicate that SAP-1 expression is downregulated during the dedifferentiation of human HCC, and that this downregulation may play a causal role in disease progression.

Adult↗

PubMed2003

Interaction of oxidative stress and inflammatory response in coronary plaque instability: important role of C-reactive protein.

OBJECTIVE: C-reactive protein (CRP), a predictor of cardiovascular events, localizes in atherosclerotic arteries and exerts proinflammatory effects on vascular cells. Reactive oxygen species (ROS) have been implicated in atherogenesis and plaque instability. METHODS AND RESULTS: Expressional pattern of CRP in directional coronary atherectomy specimens from 39 patients was examined. Characteristics of histological plaque instability and higher levels of serum CRP and fibrinogen were associated with the CRP immunoreactivity. In situ hybridization revealed the presence of CRP mRNA in coronary vasculature. Furthermore, the expression of CRP mRNA and protein was detected in cultured human coronary artery smooth muscle cells (CASMCs) by reverse transcriptase-polymerase chain reaction and Western blotting. In addition, CRP was frequently colocalized with p22phox, an essential component of NADH/NADPH oxidase, which is an important source of ROS in vasculature. Moreover, the incubation of cultured CASMCs with CRP resulted in the enhanced p22phox protein expression and in the generation of intracellular ROS. CONCLUSIONS: The expression of CRP in coronary arteries was associated with histological and clinical features of vulnerable plaque, and it had a prooxidative effect on cultured CASMCs, suggesting that it might play a crucial role in plaque instability and in the pathogenesis of acute coronary syndrome via its prooxidative effect.

Arteritis↗

PubMed2003

Immunohistochemical localization of endothelial cell-derived lipase in atherosclerotic human coronary arteries.

OBJECTIVE: A novel lipoprotein lipase (LPL)-like gene, endothelial cell-derived lipase (EDL), was recently cloned from vascular endothelial cells. The presence of LPL in the vascular wall has been implicated in the progression of atherosclerosis through the bridging function between lipoprotein particles and matrix proteoglycans to enhance lipoprotein uptake into the vascular wall. The aim of this study was to investigate the local expression of EDL in human coronary arteries. METHODS AND RESULTS: Human coronary arterial specimens from 10 autopsied cases were examined by immunohistochemistry with polyclonal antibodies against specific synthetic EDL peptides. Immunohistochemical analysis revealed that EDL was expressed in endothelial cells and medial smooth muscle cells in non-atherosclerotic coronary arteries. In addition, EDL was expressed in infiltrating cells within atheromatous plaques as well as endothelial and smooth muscle cells. Double labeling immunofluorescence confirmed EDL positive-cells were endothelial cells, smooth muscle cells and macrophages. EDL immunoreactivity was also detected in neovasculature within atheromatous plaques in atherosclerotic coronary arteries. CONCLUSIONS: These results suggest that EDL may have unique functional roles in the pathogenesis of coronary artery diseases such as atherosclerosis as well as in lipid metabolism in the vessel wall.

Aged↗

PubMed2003

Expression of progenitor cell markers in livers with fulminant massive necrosis.

Studies of stem cells in various organs have greatly progressed, and progenitor cells have been confirmed even in liver by recognition of cytokeratin 14 (CK14), c-kit, flt-3, and CD34. We, therefore, immunohistochemically examined the expression of these progenitor cell markers in patients with confluent or massive necrosis, in addition to CK19, albumin, vimentin, and Ki-67. Our subjects were six survivors and 14 deceased patients. Expression of CK14 and c-kit was found in a small number of cells lining biliary ductule-like structures, and that of flt-3 was found in many lining cells in two deceased patients with multi-lobular necrosis. CK14 positive cells were positive for c-kit, flt-3, and CK19 in semi-serial sections, but were negative for albumin, Ki-67, and CD34. In conclusion, expression of CK14 and c-kit was found in a small number of cells lining biliary ductule-like structures, and that of flt-3 was found in many cells lining biliary ductule-like structures. CK14-positive cells were positive for c-kit, but negative for CD34. Since c-kit is a hematopoietic marker, our study suggests that CK14- and c-kit-positive cells may be derived from bone marrow in liver with fulminant hepatitis.

Journal Article↗

PubMed2003

Hepatitis B virus DNA in anti-HBe-positive asymptomatic carriers.

OBJECTIVES: We examined the level of hepatitis B virus (HBV) DNA and the mutations in the precore, core and polymerase regions of HBV in sera from anti-HBe-positive asymptomatic carriers (ASC). METHODS: The amount of HBV DNA was determined semiquantitatively by mutation site-specific assay in sera from 19 anti-HBe-positive ASC and 31 HBeAg-positive patients with chronic liver disease (CLD). The mutations in the precore, core and polymerase (terminal protein) regions, spanning 1,037 nucleotides, of HBV in sera from three cases each of anti-HBe-positive ASC, HBeAg-positive ASC and HBeAg-positive CLD were examined by directly sequencing the amplified HBV DNA. RESULTS: The level of HBV viremia in anti-HBe-positive ASC was significantly lower than that in HBeAg-positive CLD patients (p < 0.01). By sequence analysis, there were a few missense mutations detected in HBeAg-positive ASC and HBeAg-positive CLD patients. In contrast, many mutations, especially in the central or N-terminal half of the core region and N-terminal part of the polymerase region, were detected in anti-HBe-positive ASC. CONCLUSION: Mutations not only in the precore/core region, but also in the polymerase region of HBV might cause damage to some important functions for efficient replication of HBV and be involved in the reduced amount of HBV in anti-HBe-positive ASC.

Adult↗

PubMed2003

PKClambda in liver mediates insulin-induced SREBP-1c expression and determines both hepatic lipid content and overall insulin sensitivity.

PKClambda is implicated as a downstream effector of PI3K in insulin action. We show here that mice that lack PKClambda specifically in the liver (L-lambdaKO mice), produced with the use of the Cre-loxP system, exhibit increased insulin sensitivity as well as a decreased triglyceride content and reduced expression of the sterol regulatory element-binding protein-1c (SREBP-1c) gene in the liver. Induction of the hepatic expression of Srebp1c and of its target genes involved in fatty acid/triglyceride synthesis by fasting and refeeding or by hepatic expression of an active form of PI3K was inhibited in L-lambdaKO mice compared with that in control animals. Expression of Srebp1c induced by insulin or by active PI3K in primary cultured rat hepatocytes was inhibited by a dominant-negative form of PKClambda and was mimicked by overexpression of WT PKClambda. Restoration of PKClambda expression in the liver of L-lambdaKO mice with the use of adenovirus-mediated gene transfer corrected the metabolic abnormalities of these animals. Hepatic PKClambda is thus a determinant of hepatic lipid content and whole-body insulin sensitivity.

Animals↗

PubMed2003

Different apoptotic regulation of TRAIL-caspase pathway in HBV- and HCV-related hepatocellular carcinoma.

Human hepatocellular carcinoma (HCC) appears to be strongly associated with apoptosis and its breakdown may be involved in the occurrence of HCC. Like the Fas/Fas-L system, the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) transduces apoptosis in a number of cancers; it is also a clinical candidate for cancer therapy. To examine its applicability in future therapy, the apoptotic pathway through TRAIL was investigated in HBV- and HCV-related HCC that have different mechanisms of hepatocarcinogenesis. Caspase-3 activity and the expression of four types of TRAIL receptor mRNAs were quantitated in tumor and contiguous non-tumor tissues obtained from 27 patients with HCC (HBV-related in 10; HCV-related in 17). The expression of caspase-3 and TRAIL receptors was also examined immunohistochemically. A significantly positive correlation was observed between caspase-3 activity and TRAIL-R1, -R2. Caspase-3 activity and TRAIL-R1, -R2 expression in tumor tissue were significantly lower than those in non-tumor tissue in HBV-related HCC. Some HCV-related HCC cases, however, demonstrated elevated caspase-3 activity and TRAIL-R1, -R2 expression in tumor tissue. HBV-related HCC demonstrated significantly suppressed caspase-3 activity, signifying apoptosis. Both TRAIL-R1 and -R2 showed coefficient correlation with caspase-3 activity, and were strongly associated with apoptosis in human HCC.

Apoptosis↗

PubMed2003

A case of well-differentiated hepatocellular carcinoma arising in primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is a chronic progressive, autoimmune liver disease that increases the risk of hepatobiliary malignancies at a late stage. We report a 66-year-old woman with PBC combined with hepatocellular carcinoma (HCC) accompanied by hypoglycemia. Two large tumors were detected on admission and the patient died because of tumor rupture and subsequent liver failure. Histological analysis revealed well-differentiated HCC in both of the tumors. Sometimes the patient had suffered from hypoglycemic attacks of unknown origin, but serum immunoreactive insulin (IRI) was within the normal range. It was interesting that such large well-differentiated hepatocellular carcinomas were generated in PBC.

Aged↗

PubMed2003

Expression and localization of ecto-nucleotide pyrophosphatase/phosphodiesterase I-3 (E-NPP3/CD203c/PD-I beta/B10/gp130RB13-6) in human colon carcinoma.

Ecto-nucleotide pyrophosphatase/phospho-diesterase-I enzyme (E-NPP), one of the type II transmembrane proteins, cleaves phosphodiester and phosphosulfate bonds of a variety of substrates including deoxynucleotides, NAD, and nucleotide sugars. Mammalian E-NPP consists of three closely related family proteins; E-NPP1 (PC-1), E-NPP2 (PDNP2/PD-Ialpha/autotaxin), and E-NPP3 (CD203c/PDNP3/PD-Ibeta/B10/gp130RB13-6) that express in different cells or at different locations even in the same cell. E-NPP3 is associated with malignant subversion and invasive properties. In this study, the expression and localization of E-NPP3 were investigated in human colon carcinoma. Western blotting showed strong E-NPP3 expression in cancer tissues and in the serum of colon carcinoma patients. Immunohistochemically, E-NPP3 was expressed not only in the apical but also in the basolateral plasma membranes of cancer cells. No prominent pattern of intracellular localization, and no relation between clinical stage and E-NPP3 expression were observed. Our results suggested that E-NPP3 is associated with carcinogenesis of human colon cancer and that serum E-NPP3 might be a tumor marker of colon carcinoma.

Colonic Neoplasms↗