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Biomedical subjects

G Yamada

Publications and source records attributed to G Yamada.

At least 91 records · Page 5Linked to original sources

[Glucocorticosteroid therapy in bronchial asthma].

Corticosteroid inhibits airway inflammation associated with eosinophils and lymphocytes in bronchial asthma. Asthma severity is classified according to symptoms, airflow obstruction (PEF) and treatment requirement. Step 1: A patient has mild asthma. Inhaled corticosteroid, beclomethasone dipropionate (BDP), is used not to exceed 200 micrograms a day. Step 2: A patient has moderate asthma. The primary therapy is 200-400 micrograms of BDP a day. Step 3: If the patient experiences exacerbations, 400 to 1000 micrograms of BDP a day are required. Step 4: A patient has severe asthma. Oral corticosteroid and/or 800-1600 micrograms of BDP are available. Intravenous corticosteroid therapy for acute exacerbation of asthma is applied for patients who have moderate or severe exacerbation. Corticosteroids are currently the most effective anti-inflammatory drugs for the treatment of asthma. Corticosteroids, however, have many sort of adverse effects. Adverse effects of inhaled corticosteroids are less than those of oral corticosteroid except for local effects. Use of spacer and gargle after the inhalation are recommended to reduce the local adverse effects.

Administration, Inhalation↗

Localization of hepatitis C viral RNA and capsid protein in human liver.

In the livers of patients whose sera contained antibodies to C100-3 antigen (anti-HCV) and hepatitis C virus (HCV) RNA, the presence of HCV RNA and HCV capsid protein (CP) antigen was demonstrated by in situ hybridization and immunohistochemistry, respectively. It was found that occasional hepatocytes in four of ten livers from patients whose sera were positive for both anti-HCV and HCV RNA hybridized with antisense as well as sense oligonucleotide DNA probes, whereas the probes did not hybridize with livers from patients whose sera were negative for anti-HCV and HCV RNA. Monoclonal antibody against a synthetic oligopeptide with amino acid sequence of HCV CP reacted with occasional hepatocytes in six of 14 livers from patients whose sera contained these HCV markers, but not with livers from patients whose sera were negative for both of them. These results suggest that HCV proliferates within hepatocytes since both antisense and sense probes hybridized with cytoplasm of the hepatocytes and that the virus matures in the cytoplasm as the capsid proteins were also found in the hepatocytes.

Adult↗

Distribution of asialoglycoprotein receptor in human hepatocellular carcinoma.

Altered expression of asialoglycoprotein (ASGP) receptors on hepatocytes has been reported during hepatic neoplasia mostly in animal models. In this study, we examined immunohistochemically the distribution of the ASGP receptor in humans with various liver diseases, including ten cases of hepatocellular carcinoma (HCC). In livers of acute hepatitis, chronic hepatitis, cirrhosis and the non-cancerous tissues (mostly cirrhosis) adjacent to HCC, the receptor was present in its normal distribution, i.e. mostly along the sinusoidal margin and partly on the lateral surface of hepatocytes. In four of six well-differentiated HCCs, the receptor was also normally distributed on the plasma membrane; by immunoelectron microscopy, it was seen in the endoplasmic reticulum and in pits in the plasma membrane but not on bile canaliculus-like structures, suggesting that it was synthesized, transported, and integrated into the plasma membrane in a polar manner. In contrast, there was no surface expression of the ASGP receptor in the remaining six HCCs (two well-differentiated and four poorly differentiated). In two of the poorly differentiated HCCs, the receptor, although absent from the cell surface, was prominent in the endoplasmic reticulum, suggesting disturbed transport of the ASGP receptor to the cell surface. When we examined proliferative activity of HCCs by immunohistochemical labeling of DNA polymerase alpha, HCCs with high percentages (above 30%) of DNA polymerase alpha-positive cells had lost the cell-surface expression of the receptor. Thus, the expression of the ASGP receptor in human HCC appears to be closely related to differentiation and proliferative activity of the tumor cells.

Aged↗

Quantitative hepatitis C virus RNA and liver histology in chronic hepatitis C patients treated with interferon alfa.

Seventy patients with hepatitis C virus (HCV) infection received alpha interferon at doses ranging from 3 to 10 million units (MU) daily for eight weeks, three times weekly for 12-24 weeks, or daily and three times weekly for 12-24 weeks. The efficacy of interferon was closely related to the initial blood HCV-RNA values in that these were lower in those who responded completely and partially compared with non-responders. Continuous reductions in HCV-RNA and improvements in the histology activity index score were seen in those who responded completely. In contrast, most of the partial and non-responders remained HCV-RNA positive.

Drug Evaluation↗

Malignant pheochromocytoma with hepatic metastasis diagnosed 20 years after resection of the primary adrenal lesion.

A 59-year-old woman developed multiple hepatic tumors 20 years after resection of pheochromocytoma of the left adrenal gland. Thin-needle aspiration biopsy of the tumor at segment 2 of the liver under ultrasound control showed histology compatible to pheochromocytoma. Then, on the basis of the diagnosis of hepatic metastasis of malignant pheochromocytoma, transcatheter arterial embolization (TAE) was performed for the purpose of the treatment of hepatic metastasis. After TAE, the size of the hepatic metastatic lesions was decreased. The present case suggests the necessity of long-term follow-up in pheochromocytoma cases.

Aclarubicin↗

Evaluation of antibody against AR142, a synthetic peptide derived from the core sequence of hepatitis C virus, in the diagnosis of non-A, non-B chronic liver disease.

We evaluated serum anti-hepatitis C virus (HCV) using a synthetic peptide (AR142) which includes an epitope in the core region of HCV. The incidence of anti-AR142 in 98 patients with type non-A, non-B chronic liver diseases (NANB-CLD) was 89.8%, while all the 28 patients with non-type C chronic liver diseases were negative for anti-AR142. Among 98 NANB-CLD patients, 74 were positive for both anti-AR142 and anti-C100-3, 23 showed discordant results, and one was positive for neither. Eighty-one NANB-CLD patients underwent reverse transcription-polymerase chain reaction assay to detect viremia and 76 (93.8%) had a detectable level of HCV-RNA. Titers of anti-AR142 were not different among groups of different disease activities, genotypes of HCV, nor amount of serum HCV-RNA. These observations suggest that anti-AR142 could be a useful marker for chronic HCV infection.

Adult↗

Immunological mechanism of chronic liver injury in viral hepatitis.

Chronic hepatitis B and chronic hepatitis C centering on immunohistochemical studies of the liver were investigated as possible mechanisms of the chronicity of viral hepatitis. Although liver cell injury was presumed to be caused by CTL in both chronic hepatitis B and C, other mechanisms of cell injury were also presumed with chronic hepatitis, type C, including autoimmune mechanisms.

Antigens, Viral↗

[Intrahepatic detection of HCV.RNA by in situ hybridization].

Recent progress of in situ hybridization techniques for detecting hepatitis C virus (HCV) RNA in liver specimens is described. Intrahepatic replication of HCV-RNA has been identified in liver tissues of both chimpanzees and patients with HCV infection by in situ hybridization.

Animals↗

Natural course of chronic hepatitis C.

We studied 333 chronic hepatitis C patients to evaluate the natural course of this disease. Among 57 patients undergoing serial biopsies, 20 had chronic persistent hepatitis (CPH) at the first biopsy, and 10 of them progressed to chronic active hepatitis (CAH) or liver cirrhosis (LC) after 11 yr. Sixteen patients had CAH 2A, and this progressed to CAH 2B or LC in 10 cases over 9 yr. Among the 21 patients with CAH 2B, progression to LC was noted in 15 after 7 yr. Among the 100 patients observed for over 5 yr, the normalization of liver function for at least 3 yr was seen in only four patients. In two of these four patients, serum HCV-RNA was tested serially. Despite the sustained normalization of alanine aminotransferase levels, HCV-RNA continued to be detectable in one patient. We conclude that many patients with chronic hepatitis C eventually show progression of their disease after a long and symptomless course.

Adolescent↗

Cloning and expression of rat preproendothelin-3 cDNA.

We report here the cloning and expression of a rat full-length cDNA encoding preproendothelin-3 (preproET-3). The predicted rat preproET-3 consisted of 167 amino acid residues. As in other ET-family peptides, the mature rat ET-3 was predicted to be produced through unusual processing from a 41-residue intermediate, the big ET-3 in rat. Transient transfection of COS-7 cells with the cloned preproET-3 cDNA resulted in the production of mature ET-3 and this production was inhibited by phosphoramidon, a metaloprotease inhibitor. This suggested that a phosphoramidon sensitive mechanism was involved in the production of ET-3 in the transfected COS-7 cells. Northern blot analysis showed that an approximately 3.0-kb rat preproET-3 mRNA was expressed in rat tissues, including the eye ball, submandibular gland, brain, kidney, jejunum, stomach and spleen. A 2.0-kb and a 3.3-kb mRNA were also detected in the eye ball and small intestine, respectively. The distinct distribution of rat preproET-3 mRNA from that of preproET-1 mRNA suggested that ET-1 and ET-3 played different roles.

Amino Acid Sequence↗

Hepatitis type C virus infection in patients with type B chronic liver disease.

Anti-c100-3 (Ortho) was determined in the sera of 152 patients with HBs antigen-positive chronic liver diseases to assess coinfection of hepatitis B virus (HBV) and hepatitis C virus (HCV). Eleven patients (7.2%) were positive for anti-c100-3. Anti-CP-9 (Okamoto) and HCV-RNA (RT-PCR) were also examined in these 11 patients. Anti-CP-9 was detected in 7 patients and HCV-RNA was detected in all 11 patients. Four of the 11 anti-c100-3-positive patients were positive for HBe antigen (HBeAg) and others were negative. In 8 of the 11 patients, HCV was suspected to be superinfected by blood transfusion. In HBeAg-positive patients, serum glutamic pyruvic transaminase (SGPT) was elevated in relation to active replication of HBV shown by DNA-polymerase activity. The histological findings showed chronic active hepatitis, with or without cirrhosis. On the other hand, in HBeAg-negative patients, SGPT fluctuated without evidence of active replication of HBV. Active inflammation in the liver was observed in 3 of 5 HBeAg-negative patients by liver biopsy. These findings suggest that HBV might play an important role in chronic active inflammation in HBeAg-positive patients coinfected with HCV, and that HCV might be responsible for continuous inflammation in HBeAg-negative patients coinfected with HCV.

Adult↗

Evidence for fluid-phase pinocytosis of extrahepatic bile duct cells isolated from normal rats in culture.

In order to elucidate the physiological function of extrahepatic bile duct cells, we isolated epithelial cells from the rat extrahepatic bile duct by digesting resected segments of the extrahepatic bile duct with 0.15% trypsin in ice-cold Ca(2+)-free Hanks' balanced salt solution supplemented with 0.25 mM EDTA overnight. As a result, the epithelial cells were collected as aggregates and attached to culture dishes coated with type I collagen. Approximately 95% of the cells cultured for 24 hrs were found to be positive for gamma-glutamyl transpeptidase and cytokeratin-19, but negative for vimentin. These characteristics were identical to the features of rat extrahepatic biliary epithelial cells in situ. Ultrastructurally, the cells were long and columnar in configuration on the 2nd day in culture, and possessed numerous microvilli at the apical surface and well-developed junctional complexes at the lateral surface. These findings also indicate that the cells maintain an epithelial nature and are morphologically polarized. When the cells were exposed to a low dose of horseradish peroxidase (HRP) on the 2nd day in culture, which was followed by fixation and treatment with 3-3'-diaminobenzidine, HRP was found preferentially in the cytoplasmic vesicles near the apical surface. HRP was then observed in the intercellular spaces; however, the electron-dense tracer, ruthenium red, did not permeate into the intercellular spaces, and HRP was found in neither cytoplasms nor intercellular spaces when the cells were incubated in HRP-containing medium at 4 degrees C for 30 min. These results suggest that the extrahepatic bile duct epithelial cells are involved in the reabsorption of bile constituents.

Animals↗

Hepatitis C virus antibody titration in patients with chronic hepatitis C, before and after interferon treatment.

We measured hepatitis C virus antibody titers in 13 patients with chronic hepatitis C to determine whether titration of hepatitis C virus antibody was useful or not, to predict and evaluate the efficacy of interferon (IFN) treatment. During administration of IFN, hepatitis C virus titers declined in all patients. Antibody titers performed before treatment as well as just at the end of treatment did not correlate with change of the alanine aminotransferase levels during administration of IFN. Antibody titers declined continuously after treatment in 5 patients with normal alanine amino-transferase levels for over 6 months after discontinuation of IFN. Antibody titers rose again in 6 patients whose alanine aminotransferase levels fluctuated after treatment. An exceptional pattern of change occurred in 2 patients whose antibody titers declined continuously although their alanine aminotransferase levels fluctuated after treatment. Repeated titration of hepatitis C virus antibody appears to be useful for evaluating the long-term efficacy of IFN treatment.

Adult↗

Localization of hepatitis C virus RNA in human liver biopsies by in situ hybridization using thymine-thymine dimerized oligo DNA probes: improved method.

To establish the most proper method of in situ hybridization in detection of HCV-RNA in the liver, various detailed procedures were examined using frozen as well as paraffin-embedded sections of tissue derived from patients. In frozen sections of the liver from hepatitis C patients obtained at autopsy or surgery, HCV-RNA was detectable by in situ hybridization using thymine-thymine dimerized oligonucleotide DNA probes when the sections were treated with ethanol-acetic acid at first, then 0.2 N hydrochloric acid, proteinase K (0.02 u/ml) and DNase. When the paraffin-embedded liver sections were used, more intense proteinase K treatment (0.2-2 u/ml) was required to expose viral RNA and even after that, the positive HCV-RNA signals were less than those in frozen sections, because the cytoplasmic RNA in the routine paraffin-embedded sections was preserved unevenly and less than in frozen sections. These findings indicate that in situ hybridization of HCV-RNA is useful for diagnosing HCV infection and should be a potent tool for monitoring the state of virus activities during therapy. However, the liver biopsy method should be modified so that RNA is retained properly to utilize biopsies more effectively for the routine diagnosis of HCV infection.

Base Sequence↗