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Biomedical subjects

G Yamada

Publications and source records attributed to G Yamada.

At least 73 records · Page 4Linked to original sources

Efficacy of interferon alfa therapy in chronic hepatitis C patients depends primarily on hepatitis C virus RNA level.

To clarify the viral factors that may predict the therapeutic effect of interferon (IFN) in chronic hepatitis C (CHC) patients, we investigated the quantitative serum hepatitis C virus (HCV) RNA level, genotype, and liver biopsy histological features in 60 patients who were treated with 360 x 10(6) U of natural IFN-alpha for 36 to 48 weeks and for more than 12 months after therapy. A branched DNA (bDNA) assay was used to measure HCV RNA levels. All responders, defined as those individuals with normal alanine transaminase (ALT) levels at 48 weeks after therapy, had less than 2 x 10(6) HCV RNA Eq/mL before administration of IFN. Of 39 patients with RNA levels (less than 2 x 10(6) Eq/L) 23 (59.0%) were responders. The genotype was determined for each patient using type-specific polymerase chain reaction (PCR) primers. There was a significant difference in rate of response between subtype 1b and subtypes 2a and 2b (P < .0002); however, all responders had less than 2 x 10(6) Eq/L independent of genotype. In a multivariate analysis, RNA level was the most statistically significant factor affecting response to IFN. Although disease severity, as defined by histological features, was not statistically correlated with nonresponse, patients that responded to IFN tended to have less severe disease.

Adult↗

Possible sources of endothelin-1 in damaged rat brain.

We investigated the sources of endothelin-1 (ET-1) detected in the damaged brain tissue of rats after cold injury. ET-1 in the injured sites was increased 1-5 days after the injury. Physiologic observations revealed that breakdown of the blood-brain barrier occurred and that plasma-derived albumin exuded into the brain parenchyma after cold injury. Radiolabeled ET-1, which was injected into the left cardiac ventricle, was detected in the tissue at the injury site, and ET-1-like immunoreactivity was observed in the brain capillaries in the damaged tissues. TGF-beta 1, which is a tissue regeneration factor, potently induced the expression of ET-1 mRNA in cultured astrocytes. These results suggest that ET-1 is produced through a variety of ways in the damaged brain.

Animals↗

Regulated expression of Brachyury(T), Nkx1.1 and Pax genes in embryoid bodies.

Embryonic stem cells (ES) can be exploited to analyze in vitro mechanisms of cellular differentiation. We have utilized ES-derived embryoid body formation in an attempt to study cell types resulting from in vitro differentiation. To this end, a variety of molecular markers, preferably those which have been associated with regulatory events during mouse embryogenesis, was employed. Specifically, Brachyury (T), Pax-3 and Pax-6 genes as well as Nkx-1.1 were used. We could demonstrate that the expression of these genes in vitro was regulated by growth factors such as activin A or bFGF. Implications of these findings and the possible applications for identifying new genes are discussed.

Animals↗

Immunohistochemical study of the distribution of intercellular adhesion molecule-1 and lymphocyte function-associated antigen-1 in chronic type B hepatitis.

The expression of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) in the livers of 11 patients with chronic hepatitis B was studied immunohistochemically by light and electron microscopy to clarify the role of these adhesion molecules in tissue damage in chronic hepatitis B. On hepatocytes, ICAM-1 expression was confined to the bile canalicular surface when the liver inflammation was mild. In contrast, when the liver inflammation was severe, ICAM-1 was distributed on the entire surface of the hepatocyte, including the sinusoidal and lateral membranes; lymphocytes which were mostly positive for LFA-1, were often observed invading deeply among these hepatocytes. The degree of ICAM-1 expression on the hepatocytes was also related to the expression of HLA class 1 antigen. In liver showing diffuse expression of ICAM-1 on the hepatocytes, strong expression of HLA class 1 antigen was observed, and amounts of HBV in the liver were decreased. Diffuse expression of ICAM-1 and HLA class 1 antigen was mostly observed after acute exacerbation of liver inflammation. These results suggest that the ICAM-1/LFA-1 pathway is involved in the immunological mechanism responsible for liver cell damage in chronic hepatitis B.

Cell Adhesion Molecules↗

Loss of contractile activity of endothelin-1 induced by electrical field stimulation-generated free radicals.

1. Electrical field stimulation (EFS; 10 V, 10 Hz, 2 ms) of porcine coronary artery strips precontracted with 10 nM endothelin-1 (ET-1) for 5 min caused a biphasic response, consisting of a slight contraction during EFS and a marked and irreversible relaxation just after EFS. This irreversible relaxation after EFS has never been investigated. In the present study, we have investigated the mechanism of the relaxation after EFS. 2. The EFS-induced response was not affected by the presence or absence of endothelium and was insensitive to 10 microM tetrodotoxin (TTX). 3. In the presence of free radical scavengers (40 u ml-1 superoxide dismutase (SOD), 1200 u ml-1 catalase or 80 mM D-mannitol), the relaxation after EFS was significantly inhibited. Moreover, relaxation after EFS was not observed in porcine coronary artery strips precontracted with 20 mM KCl. 4. In a cascade experiment, EFS of Krebs-Ringer solution containing 10 nM ET-1 induced marked suppression of the contractile activity of ET-1 in porcine coronary artery strips, which was in accord with the observed decrease in release of immunoreactive ET-1 (ir-ET-1). This effect of EFS was significantly inhibited by each of the free radical scavengers, 3 mM vitamin C, 40 u ml-1 SOD, 1200 u ml-1 catalase and 80 mM D-mannitol. 5. The exchange of 95% O2/5% CO2 gas for 95% N2/5% CO2 gas significantly inhibited the EFS-induced decrease in release of ir-ET-1. 6. Neither superoxide anions generated by xanthine (10 JM) plus xanthine oxidase (0.1 micro ml-1) nor hydrogen peroxide (10 microM) exogenously added to Krebs-Ringer solution containing 10 nM ET-1 affected the level of ir-ET-1.7. Generation of hydroxyl radicals was detected in the EFS-applied Krebs-Ringer solution. The EFS-induced generation of hydroxyl radicals was dependent on the period of stimulation and 02-bubbling, and significant generation of hydroxyl radicals was detectable with stimulation of over 5 min.Moreover, hydroxyl radicals generated in 50 mM NaCl solution containing 10 nM ET-1 by H202 plus Fe2 , i.e. the Fenton reaction, significantly decreased the level of ir-ET-l.8. These findings suggest that oxygen-derived hydroxyl radicals generated by EFS of porcine coronary artery strips inactivate ET-1, probably by structural modification. Thus, porcine coronary artery strips precontracted with ET-1 are potently relaxed by EFS.

Animals↗

Immunoelectron microscopic localization of MHC class 1 and 2 antigens on bile duct epithelial cells in patients with primary biliary cirrhosis.

We studied the distribution of class 1 and class 2 major histocompatibility complex (MHC) antigens on bile duct epithelial cells in liver from patients with primary biliary cirrhosis (PBC) by an immunohistochemical method using monoclonal antibodies to HLA-ABC products and HLA-D subregion products (HLA-DR, -DP, -DQ). By light microscopy, the expression of MHC class 1 antigens (HLA-ABC antigens) was enhanced in PBC compared with controls. While negligible staining of MHC class 2 antigens was detected on the bile duct in controls, de novo expression of MHC class 2 antigens, as well as the coexpression of HLA-DR, HLA-DQ, and HLA-DP antigens on the bile duct epithelial cells, was observed in PBC. By electron microscopy, HLA-ABC and HLA-DR antigens were present preferentially along the basolateral domain of the cell surface of the bile duct epithelial cells and on the membrane of the endoplasmic reticulum in the cytoplasm, suggesting that these MHC antigens are synthesized by the bile duct epithelial cells in PBC. The distribution of these MHC antigens on the basolateral surface of the bile duct epithelial cells, where they are easily accessible to immunocytes, supports the idea that MHC-restricted cytotoxic T lymphocytes are involved in the bile duct injury in PBC.

Adult↗

Intrafamilial clustering of genotypes of hepatitis C virus RNA.

Hepatitis C virus (HCV)-RNA in the blood was measured by polymerase chain reaction (PCR) in 37 subjects from eight families in which 2 or more persons tested seropositive for antibodies against C100-3 or CP9. HCV-RNA was positive in 17 of 37 subjects. Two or more HCV-RNA-positive subjects were observed in six of the families. Intrafamilial HCV infection was studied by determining the HCV-RNA type (I, II, III or IV) by PCR using type-specific primers. In two families, all of the subjects showed type III infection, and in three other families, all of the subjects showed type II infection, with different types of HCV infections being observed in only one family. The HCV type was uniform in all but one. These findings suggest a possibility of intrafamilial infection between husbands and wives and between members of the same household.

Adolescent↗

[Clinical usefulness of Ga-67 scintigraphy and Ga-67 single photon emission computed tomography in sarcoidosis].

Ga-67 scintigraphy was useful in evaluating the extent and relative activity of pulmonary sarcoidosis. It is also helpful detecting the involved lesions in sarcoidosis. The Ga-67 SPECT image was more excellent than planar image, because the SPECT image was able to distinguish abnormal intrapulmonary accumulation, especially, the hilar and mediastinal lymph node accumulation from normal accumulation; sternum, vertebrae, etc, which usually overlap on the planar image. Ga-67 SPECT imaging may also be useful in the diagnosis of myocardial sarcoidosis and in the evaluation of lesions, size and response to corticosteroid therapy. Several data, however, suggest that prediction of the clinical course or the prognosis of patients with pulmonary sarcoidosis is not possible by the degree of pulmonary Ga-67 accumulation.

Cardiomyopathies↗

[Transbronchial lung biopsy (TBLB) and scalene node biopsy in sarcoidosis].

The efficacy of transbronchial lung biopsy (TBLB) for the diagnosis of sarcoidosis was compared to that of scalene node biopsy (SNB). We performed both TBLB and SNB or in 336 consecutive patients with clinical features of sarcoidosis. In 270 out of 336 patients epithelioid cell granuloma was found. The frequency of granuloma in specimens obtained by TBLB was higher than that of SNB at any radiographic stage. In stage 0 and stage I diseases however, the frequency of epithelioid cell granuloma in the specimens was increased by examining both of TBLB and SNB. We concluded that SNB was useful in consecutive patients with sarcoidosis in whom the epithelioid cell granuloma could not be confirmed by TBLB.

Biopsy↗

[Corticosteroid treatment in pulmonary sarcoidosis].

Indication, dose and duration of corticosteroids in treating pulmonary sarcoidosis have discussed. Although corticosteroids are effective in improving the chest X-ray findings of sarcoidosis patients with in short term treatment, it is doubtful that corticosteroids affects the clinical course of sarcoidosis and are beneficial with long term treatment. It is agreed that asymptomatic patients with Stage I should not be treated while symptomatic patients with Stage II and Stage III should be treated. Asymptomatic patients with Stage II and Stage III need to be followed closely. The initial dose of treatment is 30 mg prednisone daily, and this is gradually reduced to the maintenance level of 10 to 15 mg. The total duration of prednisolone treatment is about 1.5 year or even more.

Adrenal Cortex Hormones↗