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Biomedical subjects

S Fujiyama

Publications and source records attributed to S Fujiyama.

119 records · Page 7Linked to original sources

Combination therapy with ursodeoxycholic acid and colchicine for primary biliary cirrhosis.

Twelve patients with primary biliary cirrhosis (PBC), stages I to III, received long-term therapy with a combination of 600 mg ursodeoxycholic acid (UDCA) and 1 mg colchicine given daily for more than 2 years. Drug toxicity was mild; one patient experienced diarrhoea that was probably due to colchicine. Serum levels of bilirubin, alkaline phosphatase (ALPase), gamma-glutamyl transpeptidase and alanine aminotransferase decreased by more than 50% of the initial values. Serum albumin and cholesterol levels also improved, but immunoglobulins and anti-mitochondrial antibody titre did not change. Histologic features in the eight patients who received serial liver biopsies before and 2 years after the beginning of treatment were evaluated. Piecemeal necrosis and portal inflammation were improved, but there was no change in portal fibrosis. Patients were divided into two groups; the first received both drugs from the outset, and the second group were started on UDCA for 3 months followed by the addition of colchicine. After 3 months, the improvement in serum bilirubin and ALPase in the first group was greater than in the second. However, in the second group, the ALPase levels had decreased significantly when measured at 6 and 9 months after the treatment compared with the levels at 3 months. These findings suggest that UDCA and colchicine may have a synergistic effect. This combination therapy appears to be safe and effective, both clinically and histologically, for treating PBC.

Colchicine↗

Intrafamilial transmission of hepatitis C virus.

The intrafamilial transmission pattern of hepatitis C virus (HCV) was examined in 118 family members of 61 index patients with type C chronic liver disease using anti-HCV antibodies and HCV RNA assay. The study subjects consisted of eight parents, 49 spouses, 50 children, eight siblings and three other relatives. The positivity rates of anti-C100, anti-JCC, second-generation anti-HCV and HCV RNA were 6.8, 12.7, 12.7 and 11.0%, respectively. Positivity in one or more anti-HCV antibody assay was detected in 3/24 (12.5%) father-child pairs, 3/17 (17.6%) mother-child pairs, 2/8 (25%) sibling pairs, 6/38 (15.8%) husband-wife pairs and 2/13 (15.4%) wife-husband pairs. In spouses, positivity for anti-HCV antibody or HCV RNA was observed after 40 years of age. None of 11 spouses married < 15 years was positive for any anti-HCV assay or HCV RNA. In spouses whose age was > 50 years and duration of marriage was > 25 years, anti-HCV or HCV RNA was frequently detected (32.0%). However, when seven pairs involving four spouses, one mother-daughter pair and two sibling pairs were subtyped, the same HCV subtypes were found in only four pairs (type II in three pairs and type III in one pair). Further, the agreement rate between anti-HCV and HCV RNA was > 90%. These results suggest that intrafamilial transmission of HCV, revealed by the subtyping method, is considered lower than the percentage of positivity for anti-HCV antibodies or HCV RNA in family members of patients with type C chronic liver disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Clinical usefulness of an assay for hepatitis C virus core in the diagnosis of non-A, non-B hepatitis and monitoring of the response to interferon therapy.

The clinical utility of a new JCC-2 enzyme-linked immunosorbent assay kit that detects and quantitates anti-hepatitis C virus (anti-HCV) core antibodies (anti-HCc) was investigated. Serum samples were obtained from 102 patients with various non-A, non-B liver diseases, including 19 cases of chronic hepatitis type C who had been treated with interferon (IFN). The results of the anti-JCC-2 assay were significantly correlated with serum HCV-RNA positivity. Patients who were HCV-RNA positive exhibited a high rate of positivity for anti-JCC-2 (72.2% in acute hepatitis, > 90% in chronic liver diseases). The geometric mean of the anti-JCC-2 titre was not significantly different among different stages of chronic liver disease (among CPH, CAH and LC). The anti-JCC-2 titre decreased gradually in cases that became HCV-RNA negative after IFN therapy. If HCV-RNA positivity recurred, the anti-JCC-2 titre increased, indicating that serial measurements of the anti-JCC-2 titre are useful for monitoring the antiviral effect of IFN treatment. These results suggest that quantification of anti-HCc by the anti-JCC-2 assay is superior to the semi-quantification of circulating HCV-RNA provided by monitoring of IFN therapy. Monitoring of HCV-RNA status using reverse transcription-nested polymerase chain reaction (RT-nested PCR) is possible, but it is technically demanding and too expensive for routine clinical use.

Adolescent↗

Immune response after hepatitis A vaccination in haemodialysis patients: comparison with hepatitis B vaccination.

This study evaluates the immune response of 20 haemodialysis (HD) patients vaccinated with hepatitis A (HA) vaccine and eight patients vaccinated with hepatitis B (HB) vaccine. Twenty patients and 22 healthy adults were immunized three times (months 0, 1 and 6) intramuscularly with a 0.5 microgram dose. All members of both groups were positive for the antibody to hepatitis A virus (anti-HAV) after three vaccinations. The geometric mean titres at 7 months were similar in both groups. No serious side effects were observed. Eight of the HD patients with HA vaccination were injected with yeast-derived hepatitis B vaccine. The three doses of 10 micrograms were administered intramuscularly at 0, 1 and 6 months. The occurrence of antibody to hepatitis B surface antigen (anti-HBs) was late in HD patients and the anti-HBs level in HD patients was lower than that in healthy subjects. These results indicate that this HA vaccine has good immunogenicity compared with the HB vaccine and that the standard three doses of HA vaccine given at 0, 1 and 6 months are safe and effective even in HD patients.

Adult↗

Clinical evaluation of titration of hepatitis C virus core antibody and its subclasses.

Titrations of anti-hepatitis C core (anti-HCc) immunoglobulin G (IgG) antibodies and its subclasses were studied in 90 patients with acute and chronic hepatitis C virus (HCV) infection, including 27 patients who underwent interferon (IFN) therapy. The positivity rates for each anti-HCc subclass were as follows: 95.2% for IgG1, 12.0% for IgG2, 69.9% for IgG3 and 19.3% for IgG4. The total anti-HCc IgG titre correlated well with the IgG1, titre, indicating that IgG1 was the main virus-specific IgG. Changes of IgG1 production mainly contributed to fluctuations of the anti-HCc IgG titre and corresponded well to positivity for HCV-RNA during and after IFN therapy. IgG3 was detected prior to IgG1 during the early phase of acute hepatitis in some cases and also appeared with relapse after IFN therapy. The serial assay of anti-HCc subclasses showed the patients' humoral immune response to HCV infection, and might be useful for evaluation of anti-viral immunity influenced by IFN therapy.

Acute Disease↗

A sensitive enzyme-linked immunosorbent assay of serum ornithine carbamoyltransferase.

Ornithine carbamoyltransferase (OCT), a urea cycle enzyme, is located almost exclusively in liver mitochondria. We designed a sensitive enzyme-linked immunosorbent assay (ELISA) of serum OCT protein using an antibody against purified bovine enzyme. OCT protein measured using this method showed a good correlation with OCT activity (r = 0.961), and was much higher in patients with liver diseases than in the controls. Measurements of serum OCT protein in 442 healthy blood donors gave the upper limit of normal range of 23 ng Eq/ml (equivalent to the bovine enzyme) for males, 8 ng Eq/ml for females, and 16 ng Eq/ml for males plus females. The values differ significantly between the sexes and depending on ages. This ELISA system is expected to be used as a pertinent liver function test.

Adolescent↗

Clinical evaluation of serum ornithine carbamoyltransferase by enzyme-linked immunosorbent assay in patients with liver diseases.

We developed a sensitive enzyme-linked immunosorbent assay (ELISA) for serum ornithine carbamoyltransferase (OCT) protein, and examined serum OCT concentrations in patients with various liver diseases. OCT concentrations were markedly elevated in cases of hepatic encephalopathy, 'acute on chronic', and those with the acute phase of acute hepatitis, moderately in chronic hepatitis, liver cirrhosis, hepatocellular carcinoma, primary biliary cirrhosis, and slightly in those with a fatty liver. High percentages (92-98%) of patients with chronic hepatitis, liver cirrhosis and hepatocellular carcinoma had higher than normal concentrations of serum OCT protein. There was a close correlation with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities and moderate correlations with those of mitochondrial AST, glutamate dehydrogenase and gamma-glutamyltranspeptidase. The OCT/ALT ratio was higher in patients with liver cirrhosis than in those with chronic hepatitis (p < 0.001), and was still higher in cases of hepatocellular carcinoma (p < 0.05). In 2 patients with 'acute on chronic' disease, OCT concentrations decreased similarly with or more rapidly than AST or ALT activities after admission. In 2 patients with hepatic encephalopathy, the OCT concentrations changed similarly with AST and ALT activities. This OCT ELISA system will aid in diagnosing various liver diseases and in the follow-up of the patients, and the OCT/ALT ratio may serve for a differential diagnosis of liver diseases.

Adult↗

Enzyme-linked immunosorbent assay of carbamoylphosphate synthetase I: plasma enzyme in rat experimental hepatitis and its clearance.

Carbamoylphosphate synthetase I (CPS I), a urea cycle enzyme, is located almost exclusively in the mitochondria of hepatocytes. The enzyme is unique in that it constitutes about 2-6% of total liver protein and is composed of a large subunit of 160 kD. We developed a sensitive enzyme-linked immunosorbent assay (ELISA) for measurement of the enzyme in plasma using an antibody against the rat enzyme. In galactosamine-induced rat acute hepatitis, plasma concentration of CPS I that was 1-2 micrograms/ml blood before the treatment, increased up to 125 micrograms/ml blood in 24 h after the treatment and decreased to a near control level in 72 h. Plasma concentration of ornithine carbamoyl-transferase (OCT), another urea cycle enzyme, reached a maximum in 24 h and then decreased a little more rapidly than that of CPS I. On the other hand, alanine aminotransferase activity reached a maximum in 36 h and decreased to a normal level in 96 h. In immunoblot analysis, the native CPS I polypeptide of 160 kD and its fragments of 140 and 125 kD were detected 24-48 h after the treatment. When purified rat CPS I and bovine OCT were injected intravenously into rats, the enzymes disappeared from blood roughly exponentially with apparent half-lives of about 67 and 18 min, respectively. Development of an ELISA for human CPS I and determination of the serum enzyme in various liver diseases remain to be performed.

Acute Disease↗

Gastric mucosal hexosamine contents in patients with renal diseases.

Since gastric mucosal lesions are frequently encountered in patients with renal disease, we measured the gastric mucosal hexosamine (Hx) content in 51 patients with renal disease. Endoscopic examination revealed that nearly half of the patients had erosive gastritis, and that duodenal ulcers (Dus) were more common than gastric ulcers (Gus). The gastroduodenal lesions were increased in patients with advanced renal dysfunction. The relationship between Hx content and various indicators of renal function, including creatinine clearance (Ccr), serum creatinine (cr), blood urea nitrogen (BUN), and 24-h urine protein excretion, were also evaluated. The Hx content decreased in the early stage of renal dysfunction. However, it returned to normal to near normal levels in advanced renal disease and patients who underwent hemodialysis. Since the Hx content was decreased in the early stage of renal dysfunction, careful follow-up appears to be necessary in patients with renal disease.

Adolescent↗

Early detection of hepatocellular carcinoma associated with cirrhosis by combined assay of des-gamma-carboxy prothrombin and alpha-fetoprotein: a prospective study.

BACKGROUND/AIMS: To evaluate the usefulness of des-gamma-carboxy prothrombin (DCP) assay in a group of high risk for hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Plasma DCP and serum-alpha-fetoprotein (AFP) concentrations were prospectively measured in 137 patients with liver cirrhosis (LC). RESULTS: During the mean observation period of 3.4 years, HCC developed in 35 patients (25.5%; yearly rate 7.5%), of whom 16 (45.7%) had a small tumor < or = 2 cm in diameter. Eight patients (22.9%) had significantly elevated DCP at the time of HCC detection. However, all these tumors measured > 2 cm and were multiple or diffuse type. In cases with a tumor diameter < or = 2 cm HCC was diagnosed by imaging and elevated AFP concentrations. In contrast, elevated DCP frequently leads to the detection of tumors > 2 cm or those of diffuse type, which are difficult to recognize with imaging. CONCLUSIONS: Thus, although DCP alone is not sensitive enough to detect early small liver cancers, the use of both markers and imaging in the follow-up of patients with LC might be beneficial.

Adult↗

Zinc absorption and its correlation with results of oral zinc tolerance testing in nonalcoholic liver cirrhosis; kinetic study.

BACKGROUND/AIMS: Liver cirrhosis is often complicated by symptoms of zinc deficiency, i.e., disturbances of taste and smell, skin eruptions, and other symptoms. We evaluated zinc absorption in patients with nonalcoholic liver cirrhosis to clarify the cause of zinc deficiency. METHODS AND MATERIALS: The absorption of zinc was calculated from the results of both the oral and intravenous zinc loading tests. RESULTS: Absorption was significantly reduced the cirrhotic patients, 20.4 +/- 10.7% as compared with the controls, 38.3 +/- 11.0%. In the cirrhotic patients with hepatocellular carcinoma, it was 17.8 +/- 9.3%, not significantly different from that of cirrhotics without hepatocellular carcinoma, 24.1 +/- 10.7%. CONCLUSIONS: Therefore, the development of hepatocellular carcinoma in patients with nonalcoholic liver cirrhosis had no influence on zinc absorption. Because a lower correlation between zinc absorption and the results of oral zinc tolerance testing was observed, the oral zinc tolerance test alone cannot be used as an accurate procedure for evaluating zinc absorption in liver cirrhosis. One should thus use both the intravenous as well as the oral zinc loading test when evaluating zinc absorption.

Absorption↗