Biomedical subjects

Yoshitake Hayashi

Publications and source records attributed to Yoshitake Hayashi.

50 records · Page 3Linked to original sources

PubMed2003

Morphologic, flow cytometric and cytogenetic evaluation of bone marrow involvement in B-cell lymphoma.

BACKGROUND AND OBJECTIVES: Flow cytometric immunophenotypic analysis (FC) and cytogenetic analysis are essential techniques for the diagnosis and classification of many hematologic disorders. The roles of these analyses in B-cell lymphoma to detect bone marrow (BM) involvement in clinical staging and to evaluate the effectiveness of treatments have not yet been determined. The aim of this study was to evaluate the usefulness of FC and cytogenetic analysis in the assessment of BM involvement in B-cell lymphoma. DESIGN AND METHODS: We retrospectively analyzed the usefulness of three-color FC and cytogenetic analysis in detecting BM involvement by examining 104 BM specimens from patients with B-cell lymphoma. RESULTS: By morphologic evaluation of BM biopsy (BMB), the BM was involved in 11 specimens (10.6%), not involved in 92 specimens (88.5%) and involvement could not be determined in 1 specimen (0.9%). FC identified a monoclonal B-cell population in 24 samples (23.1%). FC detected BM involvement in all but one BMB positive sample, and showed negative results in a BMB undetermined sample. Conclusively, FC found a monoclonal B-cell population in 14 of 92 BMB negative samples (15.2%). In particular, FC detected smaller amounts of BM involvement than did morphologic evaluation. Cytogenetic analysis revealed clonal abnormalities in only 9 of 104 samples (8.7%). However, 2 of these 9 samples were from patients with aggressive lymphoma with complex structural chromosomal abnormalities detectable only by cytogenetic analysis. INTERPRETATION AND CONCLUSIONS: Although morphologic evaluation of adequate amounts of BMB specimens remains essential for the evaluation of BM involvement, three-color FC is more sensitive in detecting BM disease than morphologic or cytogenetic analysis. Cytogenetic analysis seems to have low sensitivity and specificity, but this method may improve the detection of BM involvement in a small number of aggressive lymphomas that have many mitotic cells.

B-Lymphocytes↗

PubMed2002

Superoxide generation in directional coronary atherectomy specimens of patients with angina pectoris: important role of NAD(P)H oxidase.

OBJECTIVE: NADH/NADPH oxidase is an important source of reactive oxygen species (ROS) in the vasculature. Recently, we demonstrated that p22(phox), an essential component of this oxidase, was expressed in human coronary arteries and that its expression was enhanced with the progression of atherosclerosis. The present study was undertaken to investigate its functional importance in the pathogenesis of coronary artery disease. For this aim, the expression of p22(phox), the distribution of oxidized low density lipoprotein (LDL), and the generation of ROS in directional coronary atherectomy (DCA) specimens were examined. METHODS AND RESULTS: DCA specimens were obtained from patients with stable or unstable angina pectoris. The distribution of p22(phox) and of oxidized LDL was examined by immunohistochemistry. The generation of superoxide in DCA specimens was assessed by the dihydroethidium method and lucigenin-enhanced chemiluminescence. ROS were closely associated with the distribution of p22(phox) and oxidized LDL. Not only inflammatory cells but also smooth muscle cells and fibroblasts generated ROS. There was a correlation between ROS and the expression of p22(phox) or oxidized LDL. The generation of ROS was significantly higher in unstable angina pectoris compared with stable angina pectoris. CONCLUSIONS: ROS generated by p22(phox)-based NADH/NADPH oxidase likely mediate the oxidative modification of LDL and might play a major role in pathogenesis of atherosclerotic coronary artery disease.

Angina Pectoris↗

PubMed2002

Negative regulation of platelet clearance and of the macrophage phagocytic response by the transmembrane glycoprotein SHPS-1.

SHPS-1 is a receptor-type glycoprotein that binds and activates the protein-tyrosine phosphatases SHP-1 and SHP-2, and thereby negatively modulates intracellular signaling initiated by various cell surface receptors coupled to tyrosine kinases. SHPS-1 also regulates intercellular communication in the neural and immune systems through its association with CD47 (integrin-associated protein) on adjacent cells. Furthermore, recent studies with fibroblasts derived from mice expressing an SHPS-1 mutant that lacks most of the cytoplasmic region suggested that the intact protein contributes to cytoskeletal function. Mice homozygous for this SHPS-1 mutation have now been shown to manifest thrombocytopenia. These animals did not exhibit a defect in megakaryocytopoiesis or in platelet production. However, platelets were cleared from the bloodstream more rapidly in the mutant mice than in wild-type animals. Furthermore, peritoneal macrophages from the mutant mice phagocytosed red blood cells more effectively than did those from wild-type mice; in addition, they exhibited an increase both in the rate of cell spreading and in the formation of filopodia-like structures at the cell periphery. These results indicate that SHPS-1 both contributes to the survival of circulating platelets and down-regulates the macrophage phagocytic response.

Animals↗

PubMed2002

Development of multicentric hepatocellular carcinoma after completion of interferon therapy.

We report a case of multicentric hepatocellular carcinoma that developed in a 74-year-old man 3 and 6 years after interferon (IFN) treatment for chronic hepatitis C, despite sustained virologic, biochemical, and histological improvement. Initially, serum hepatitis C virus RNA was positive and the patients' serum level of alanine aminotransferase (ALT; 82 IU/ml) was abnormal. Hepatitis B virus (HBV) in the serum was negative for surface antigen, surface antibody, core antibody, and DNA. The patient was started on 10 x 10(6) international units (IU) of IFNalpha, 3 days a week for a total of 24 weeks. After the IFN therapy, the patient demonstrated a normal serum ALT level, and was continuously negative for HCV-RNA, and histology improved from chronic active hepatitis to chronic persistent hepatitis. Follow-up studies with ultrasonography (US) every 3 months and computed tomography (CT) every 6 months revealed no space-occupying lesion (SOL) for 3 years after IFN treatment.US-guided biopsies of two 15-mm hypoechoic SOLs in segments eight (S8) and seven (S7) 34 and 74 months, respectively, after IFN treatment showed well-differentiated hepatocellular carcinoma (HCC). Clinical data, imaging studies, and histologic examinations showed that both tumors were multicentric HCC. Further studies may provide insights into the possible role of HCV in hepatocarcinogenesis in patients demonstrating HCV eradication by IFN treatment.

Aged↗

PubMed2002

Expression of tissue transglutaminase and elafin in human coronary artery: implication for plaque instability.

BACKGROUND: the extracellular matrix (ECM) is an important determinant of plaque instability. Since tissue transglutaminase (tTG) and elafin act as stabilizing factors, they might play a crucial role in the pathogenesis of acute coronary syndrome. We examined their expression in human coronary arteries and the regulation of tTG expression in cultured vascular smooth muscle cells (SMCs). METHODS AND RESULTS: immunohistochemical studies on autopsy samples of human coronary arteries revealed the expression of tTG and elafin in the endothelium, medial SMCs, and the ECM in non-atherosclerotic coronary arteries. Their expression in SMCs, endothelium, and ECM was enhanced in atherosclerotic coronary arteries. In contrast, they were hardly detectable in accumulating macrophages or at the lipid core. Double staining demonstrated that elafin was co-localized with tTG. Moreover, some tTG-expressing cells were positive for TNF-alpha, suggesting that this cytokine might play an important role in the regulation of tTG. Treatment of cultured rat aortic SMCs with TNF-alpha increased their tTG mRNA, protein expression and enzyme activity. CONCLUSIONS: the expression of tTG and elafin increased in atherosclerotic coronary arteries. The investigation with cultured SMCs suggested that TNF-alpha might mediate the upregulation of tTG. Our findings may provide new insights into the mechanism of plaque instability and the pathogenesis of acute coronary syndrome.

Animals↗

PubMed2002

CEA producing primary hepatic carcinoid.

Imaging studies of a hepatic tumor in a 53-year-old woman with elevated serum levels of neuron-specific enolase (NSE), carcinoembryonic antigen (CEA) and 5-hydroxyindole acetic acid (5HIAA) revealed a hypervascular tumor in the right lobe. Grossly, the brownish tumor was measured 13.5x12 cm with four daughter nodules. Microscopically, the majority of these columnar and round tumor cells had ribbon-or rosette-like patterns with the expression of neuroendocrine marker proteins, such as Grimelius, NSE, chromogranin A, and synaptophysin, and moderate expression of CEA but without the expression of cytokeratin nos 7,8,14,18,19 and OV-6; the minority had glandular patterns with a strong expression of CEA but without the expression of cytokeratin nos 7,8,14,18,19 and OV-6. Ultrastructurally, most tumor cells contained populations of electron-dense core granules ranging between 100 and 200 nm in diameter. After hepatectomy, serum CEA, NSE, and 5HIAA reverted to normal ranges and persisted for 19 months. These findings suggested that the diagnosis of primary hepatic carcinoid was tenable and that the tumor might derive from hepatic stem cells which acquired the additional nature of producing CEA without cytokeratins characteristic of hepatocytes or bile duct cells. Some molecular based approaches have attributed unique biological behavior and histogenesis to this carcinoid tumor.

Journal Article↗

PubMed2002

Eosionophilic pseudotumor of the liver due to Ascaris suum infection.

A case of eosinophilic pseudotumor of the liver due to Ascaris (A) suum is described in a 34-year-old-man with a high serum level of immunoglobulin E and hypereosinophilia ascribed to a history of atopic dermatitis since childhood. Multiple hepatic hypoechoic nodules detected by ultrasound were confirmed as low-density nodules on computed tomography (CT), and as low and high signal intensity lesions on T1-and T2-weighted magnetic resonance imaging (MRI), respectively. CT during arteriography (CTA) and arterial portography revealed multiple nodules with ring-shaped enhancement and perfusion defect, respectively. Biopsied liver tissue specimens did not contain tumor cells or atypical cells; instead, they showed marked infiltration of eosinophils with necrosis and Charcot-Leyden crystals in the portal tracts and hepatic sinusoides, suggesting parasitic infection, although neither larvae nor eggs were detected. The diagnosis of visceral larva migrans (VLM) due to A. suum was based on immunoserological tests. The patient was a habitual consumer of raw bovine liver, which may explain the A. suum infection. After drug therapy with albendazole, the hypoechoic nodules disappeared. Differential diagnoses and the possible transfection route of A. suum are discussed.

Journal Article↗

PubMed2002

Histological grading and staging in chronic hepatitis: its practical correlation.

Although the histological features of various causes of chronic liver disease have been well described, usually the inflammatory activity of the disease is important after the cause has been established. Some patients have co-infection or concomitant liver disease and on occasion it is difficult to decide the treatment. In order to clarify the histological differences, we investigated the inflammatory activity among autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), chronic hepatitis C (CHC) and chronic hepatitis B (CHB) in a standardized way using the modified histological activity index (HAI). According to the modified HAI, inflammatory activity is divided into four categories; categories A/D explains portal/periportal inflammation and categories B/C explains lobular activity. The inflammatory score of AIH tended to be greater in all categories from the early stage of fibrosis, whereas scores of PBC were lower, except for portal inflammation. Chronic hepatitis C patients had portal or periportal inflammation, and their inflammatory scores were linked to the development of fibrosis. Chronic hepatitis B patients tended to have severe lobular injury, but did not have a relationship between the inflammatory score and their stage. To know the distribution of inflammation using the modified HAI scoring system may be helpful and convenient in evaluating patients with chronic inflammatory liver disease.

Adult↗

PubMed2002

Heterogeneous loss of connexin43 protein in nonischemic dilated cardiomyopathy with ventricular tachycardia.

INTRODUCTION: Gap junction alterations recently have been implicated in chronic heart failure, but direct evidence between gap junction manifestation in nonischemic dilated cardiomyopathy (DCM) is lacking. The current study examines whether qualitative changes or altered distribution of gap junctional connexin43 (Cx43) are related to global ventricular function and ventricular arrhythmia in DCM. METHODS AND RESULTS: We investigated 31 DCM patients (52 +/- 15 years) and 5 control subjects (55 +/- 10 years). Expression of Cx43 proteins was qualitatively and quantitatively determined using immunoconfocal microscopy in right ventricular biopsy specimens from each patient. The expression level of Cx43 protein was defined as the proportion of tissue area occupied by Cx43 (percent tissue area) in each test area. Cx43 immunoreactive signal expressed as percent tissue area was not correlated with the change in left ventricular ejection fraction (P = 0.17). Of 31 DCM patients, 23% subsequently developed sustained ventricular tachycardia (VT), which allowed retrospective division of the samples into two groups: non-VT and VT. Left ventricular ejection fraction was comparable in both groups, but the percent tissue area in the VT groups was significantly decreased compared with that of the non-VT groups (P = 0.03). Furthermore, Cx43 protein was distributed heterogeneously in the VT groups (P < 0.0001). CONCLUSION: Heterogeneous reduction of Cx43 protein may result in development of malignant ventricular arrhythmia in DCM.

Adult↗

PubMed2002

Regulation of the alpha-fetoprotein gene by the isoforms of ATBF1 transcription factor in human hepatoma.

We investigated mechanisms regulating expression of alpha-fetoprotein (AFP) in 3 human hepatoma cell lines, HuH-7, HepG2, and huH-1, producing high, medium, and low levels of AFP, respectively. The silencer, a negative cis-acting element of the AFP gene, was highly activated in huH-1 and HepG2 to repress AFP enhancer activity by 91%, whereas only 26% repression was observed in HuH-7. To account for the difference in AFP production between HepG2 and huH-1, we investigated the roles of two isoforms of the AT motif-binding factor 1 (ATBF1) transcription factor, ATBF1-A and -B. Cotransfection assays showed that the ATBF1 isoforms regulated the AFP gene differently in HepG2 and huH-1. In huH-1 and HuH-7, both ATBF1 isoforms suppressed strongly enhancer activity and slightly promoter activity. In HepG2, on the other hand, ATBF1-A suppressed the enhancer and promoter activities, but surprisingly, ATBF1-B was found to stimulate enhancer activity while showing no effect on the promoter. Levels of ATBF1-A mRNA were similar in all 3 cell lines, whereas the expression ATBF1-B mRNA varied greatly, with the highest level seen in HepG2 followed by huH-1 and HuH-7. These results suggest that, in HepG2, ATBF1-B may have a dominant negative effect to relieve the transcriptional repression caused by its isoform. In support of this view, we found that the N-terminal region specific to the ATBF1-A molecule possessed transcriptional repressor activity. Thus, the use of the ATBF1 variants as well as the silencer may provide a unique mechanism that contributes to the determination of AFP levels in human hepatoma cell lines.

Carcinoma, Hepatocellular↗

PubMed2002

Decreased ornithine decarboxylase activity in the kidneys of Dahl salt-sensitive rats.

To assess the roles of polyamines (putrescine, spermidine, and spermine) and ornithine decarboxylase (ODC), the rate-limiting enzyme of polyamine synthesis, in the development of salt-sensitive hypertension, we evaluated activity and expression of ODC, urinary polyamine excretion, and antizyme (endogenous ODC inhibitor protein) expression in Dahl salt-sensitive (SS) and salt-resistant (SR) rats after they were fed on a low (0.3%) or high (4%) salt diet for 4 weeks. We also examined the effects of spermidine and difluoromethylornithine (DFMO: a specific inhibitor of ODC) on the systolic blood pressure and ODC protein expression in SS rats fed a high salt diet. Renal ODC activity and urinary polyamine excretion in SS rats were lower than those in SR rats after 4 weeks treatment with a low or high salt diet. The renal ODC protein expression of SS rats was paradoxically increased as compared to the SR group. A high salt diet did not alter ODC activity but increased ODC protein only in SS rats. ODC mRNA and antizyme protein expressions were not significantly different among the four groups. Spermidine supplementation attenuated and DFMO exaggerated hypertension in SS rats fed a high salt diet. Spermidine down-regulated and DFMO up-regulated renal ODC protein in SS rats on a high salt diet. ODC activity was decreased but protein was paradoxically increased in kidneys of SS rats. ODC protein was suggested to increase in compensation for the inhibition of its activity. Impaired ODC activity and polyamine production in the kidney may exaggerate salt-sensitive hypertension in SS rats.

Animals↗

PubMed2002

Expressional changes of the vascular antioxidant system in atherosclerotic coronary arteries.

Oxidative stress induced by reactive oxygen species (ROS) plays an important role in atherogenesis, and the redox state is determined by the balance between antioxidants and the ROS generating system. To defend against enhanced ROS, mammalian cells have a complex network of antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase. To clarify the role of the vascular antioxidant system, we investigated by immunohistochemistry the expressional changes of antioxidative enzymes in coronary arteries obtained from autopsied cases. In nonatherosclerotic coronary arteries, Cu/Zn SOD and Mn SOD were expressed in medial smooth muscle cells (SMC), whereas cytosolic GPx (GPx-1) was expressed mainly in endothelium and weakly in medial SMC. Catalase was expressed in medial SMC and endothelium. Progression of atherosclerosis did not result in an additional increase in the expression of antioxidative enzymes in SMC in the media or endothelium. However, migrating SMC and macrophages in atheromatous plaques expressed these four antioxidative enzymes intensively. Double staining with cell markers confirmed the cell-specific expression of the antioxidative enzymes. Thus, the expressional pattern showed regional heterogeneity. In response to oxidative stress, the vascular antioxidant system was upregulated in atherosclerotic lesions. The imbalance between vascular antioxidant and oxidant systems might play an important role in coronary atherogenesis.

Aged↗

PubMedDate not supplied

Response to interferon-alpha in chronic hepatitis B with and without precore mutant strain detected by mutation site-specific assay.

GOALS: We investigated whether the presence of precore mutant (stop codon mutation at codon 28) affects the response to interferon-alpha in patients with chronic hepatitis B. BACKGROUND: Mutations of hepatitis B virus (HBV) may influence the response to treatment. The association of precore mutant with the response to interferon is controversial. STUDY: Thirty-one Japanese patients with hepatitis B e antigen-positive chronic hepatitis were treated with natural interferon-alpha. HBV DNA with the precore mutation was assayed in serum using a mutation site-specific assay before and after treatment. RESULTS: Before treatment, precore mutant was detected in 22 cases (group A) and not detected in 9 cases (group B). Serum HBV DNA level before treatment was not different between the 2 groups. At the end of treatment, serum HBV DNA was decreased to undetectable levels in 13% (4 of 31). Six months after treatment, the percentage of cases with loss of hepatitis B e antigen and a decrease in the transaminase level to within the normal range was significantly higher in group B than in group A (67%, 18%, P = 0.015). CONCLUSIONS: Chronic hepatitis without precore mutant strain before treatment is more responsive to IFN-alpha.

Adult↗

PubMedDate not supplied

Well-differentiated HCC manifesting hyperattenuation on CT during arterial portography.

A rare case of well-differentiated minute hepatocellular carcinoma (HCC) with hepatitis C virus-related cirrhosis, with unusual radiologic features, is presented. A 10-mm hypoechoic nodule disclosed by ultrasound in segment six showed hypoattenuation on computed tomography hepatic arteriography and hyperattenuation on computed tomography during arterial portography, indicating that the portal vein may have been the dominant vascularity of the nodule. Contrast-enhanced ultrasound revealed hypovascularity in the early arterial phase, isovascularity in the late vascular phase, and the same perfusion as that surrounding the liver parenchyma in the post-vascular phase, with the same pattern observed on the two imaging techniques. These findings were considered not compatible with those of well-differentiated HCC. Ultrasound-guided biopsy showed histological features of well-differentiated HCC with over two-fold the cellularity of the non-tumorous area with a high nuclear/cytoplasmic ratio, increased cytoplasmic eosinophilia, slight atypia and fatty change with an irregular thin trabecular pattern. Further studies may provide insights into the correlation between tumor neovascularity in multistep hepatocarcinogenesis and dual hemodynamics, including the artery and the portal vein.

Aged↗