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Biomedical subjects

S Fujiyama

Publications and source records attributed to S Fujiyama.

At least 55 records · Page 3Linked to original sources
PubMed1995

Changes in prevalence of anti-HCV antibodies associated with preventive measures among hemodialysis patients and dialysis staff.

The latest prevalence of hepatitis C virus (HCV) infection was evaluated in 548 Japanese patients undergoing hemodialysis, and 216 members of the hospital dialysis staff. An assay of anti-HCV antibodies was performed using both first- and second-generation immunoenzymatic tests, and anti-HCV specificity was confirmed with a second-generation recombinant immunoblot assay. Of 548 hemodialysis patients, 90 (16.4%) were positive with first-generation, and 166 (30.3%) with second-generation tests. These rates were significantly higher than those for either hospital staff members (0.5% and 2.3%; p < 0.01) or healthy blood donors (0.98% and 1.30%; p < 0.001). Patients with a history of blood transfusion tended to have a higher positivity rate for anti-HCV than did the non-transfused group (35.4% vs. 25.7% with second generation tests; p < 0.05). Positivity for anti-HCV was related to the duration of hemodialysis. Only a few patients seroconverted during the 2-year, 5-month period between the previous and present studies. Although hemodialysis patients remain a high-risk group for HCV infection, the prevalence of anti-HCV antibodies has decreased recently thanks to the use of erythropoietin for renal anemia, the universal screening of blood donors for anti-HCV antibodies, and improvements in infection control measures for this virus.

Adult↗
PubMed1995

Exon redefinition by a point mutation within exon 5 of the glucose-6-phosphatase gene is the major cause of glycogen storage disease type 1a in Japan.

Glycogen storage disease (GSD) type 1a (von Gierke disease) is an autosomal recessive disorder caused by a deficiency in microsomal glucose-6-phosphatase (G6Pase). We have identified a novel mutation in the G6Pase gene of a individual with GSD type 1a. The cDNA from the patient's liver revealed a 91-nt deletion in exon 5. The genomic DNA from the patient's white blood cells revealed no deletion or mutation at the splicing junction of intron 4 and exon 5. The 3' splicing occurred 91 bp from the 5' site of exon 5 (at position 732 in the coding region), causing a substitution of a single nucleotide (G to T) at position 727 in the coding region. Further confirmation of the missplicing was obtained by transient expression of allelic minigene constructs into animal cells. Another eight unrelated families of nine Japanese patients were all found to have this mutation. This mutation is a new type of splicing mutation in the G6Pase gene, and 91% of patients and carriers suffering from GSD1a in Japan are detectable with this splicing mutation.

Adult↗
PubMed1995

The role of macrophage colony-stimulating factor in the differentiation and proliferation of Kupffer cells in the liver of protein-deprived mice.

BACKGROUND: Protein calorie malnutrition is known to induce various macrophage dysfunctions, such as the impairment of their phagocytic function, proliferative capacity, and bactericidal activity. However, little is known about the behavior of Kupffer cells under protein calorie malnutrition in vivo. EXPERIMENTAL DESIGN: To investigate the behavior of Kupffer cells under protein calorie malnutrition, we fed mice on a low protein (protein-derived) diet for 4 weeks and examined the number, cytologic changes, and proliferative capacity of their Kupffer cells. To detect macrophage precursor cells, colony-forming assays were performed in the bone marrow, spleen, and liver of the mice. To investigate the relationship of Kupffer cells to CSF, the serum levels of IL-6 and granulocyte-macrophage colony-stimulating factor were measured by ELISA, and the expression of macrophage colony-stimulating factor (M-CSF) mRNA in the liver was determined by Northern blot analysis. The recovery processes of Kupffer cells in the protein-deprived mice after normal protein feeding or daily recombinant human macrophage colony-stimulating factor administration were also investigated. RESULTS: In the protein-deprived mice, Kupffer cells decreased in number to two-thirds that of the normally fed (nondeprived) mice, showed the cytologic and ultrastructural features of maturation failure, and had reduced proliferative capacity. After normal protein feeding or recombinant human macrophage colony-stimulating factor administration, the number, morphology, and proliferative capacity of the Kupffer cells in the liver returned to normal, and they matured as in the nondeprived mice. In the protein-deprived mice, the serum levels of IL-6 and granulocyte-macrophage colony-stimulating factor increased, and the expression of M-CSF mRNA in the liver was reduced. In the bone marrow, the granulocyte-macrophage colony-forming cells and macrophage colony-forming cells were increased, and the influx of monocytes into the liver was temporarily enhanced; however, the number of monocytes in the peripheral blood was decreased. CONCLUSIONS: These results suggest that the reduced production of M-CSF in the liver of protein-deprived mice results in numerical reduction, maturation failure, and decreased proliferative capacity of Kupffer cells.

Animals↗
PubMed1994

IgM and IgA antibodies generated against hepatitis C virus core antigen in patients with acute and chronic HCV infection.

Antibody subclasses directed against the core protein (HCc) of hepatitis C virus (HCV) were measured in 27 patients with acute non-A, non-B (NANB) hepatitis, and 99 patients with chronic HCV-associated liver disease. IgM, IgA, and IgG anti-HCc responses were observed in 11 (40.7%), 7 (25.9%), and 18 (67%) patients with acute NANB hepatitis, respectively. Twenty-four (24.2%) and 40 (40.4%) patients with chronic HCV infection also had detectable IgM and IgA, respectively. IgM anti-HCc inconsistently detected acute infection, and HCV ribonucleic acid (RNA) could be detected preceding the rise in anti-HCc antibodies in five consecutive patients with acute hepatitis. IgM anti-HCc also could not distinguish acute from chronic infection and did not correlate with histologic progression. However, the form of IgA present (polymeric vs monomeric) did discriminate acute from chronic infection and the IgA anti-HCc titer correlated with histologic evidence of liver disease in patients with chronic HCV infection.

Acute Disease↗
PubMed1994

Coinfection of hepatitis C virus in patients with chronic hepatitis B infection.

Enzyme-linked immunosorbent assays for detecting antibodies against hepatitis C virus and the polymerase chain reaction were tested in 82 chronic hepatitis B surface antigen carriers for their accuracy in diagnosing patients coinfected with hepatitis B and C viruses. To clarify the role of each virus in chronic hepatitis, serologic assays against hepatitis B virus were also tested. Thirteen (14.9%), 14 (17.1%) and 15 (18.3%) patients were anti-HCV positive using C100 (HCV1), JCC, and a second generation test (HCV2), respectively. HCV RNA was detected by polymerase chain reaction in 9 of 18 anti-HCV-positive cases. Although HCV1 assays were not sufficient, either the JCC or HCV2 assay detected all polymerase chain reaction-positive cases. Fifteen of 18 specimens that were positive in at least one of the three ELISA were seronegative for the hepatitis B e antigen. As judged by HBV DNA polymerase activity, titers of hepatitis B surface antigen and immunoglobulin A antibody against hepatitis B core antigen (IgA anti-HBc), activity of hepatitis B virus replication and immune response against hepatitis B virus in patients with coinfection was decreased to the level of hepatitis B virus asymptomatic carriers. These results show that hepatitis C virus appears to be the primary cause of active hepatitis in most patients with hepatitis B and hepatitis C virus coinfection.

Adolescent↗
PubMed1994

Current seroepidemiological status of hepatitis A with a comparison of antibody titers after infection and vaccination.

The overall prevalence of anti-hepatitis A virus antibodies was 49.6% in 385 inhabitants in Honda City, Japan in 1991. An approximately 50% prevalence rate occurred between 40 and 49 years of age. The prevalence of anti-HAV antibodies was significantly lower in 1991 than in 1982 in the age groups 20 to 29 years and 30 to 39 years (p < 0.01), suggesting there has been no significant HAV infection since 1982. In addition, anti-HAV antibody titers of sera from convalescent hepatitis. A patients were compared with those from seropositive healthy subjects and from healthy subjects following administration of a lyophilized inactivated hepatitis A vaccine or immune serum globulin. Titers after vaccine administration were considerably higher than after immune serum globulin and, although lower than those obtained after natural infection, should be sufficient for protection against hepatitis A virus.

Adult↗
PubMed1994

[A case of hepatocellular carcinoma whose lung metastases and tumor emboli in the inferior vena cava disappeared by oral administration of UFT].

A 65-year-old male with hepatocellular carcinoma was admitted to our hospital. Hepatic angiography showed a hypervascular tumor 8 cm in diameter in the right lobe of the liver with tumor emboli in the inferior vena cava and right atrium. Then, two chemoembolization treatments using gelform and cisplatin suspended in Lipiodol were performed. Although the size of the main tumor in the liver and tumor emboli was reduced, 6 months after the initial chemoembolization the serum levels of alfa-fetoprotein (AFP) and plasma des-gamma-carboxy prothrombin (DCP) rose to 14,000 ng/ml and 6.4 AU/ml, respectively, and multiple lung metastases were detected by CT scan. Then, 200 mg/day of UFT was administered orally. Four months after the administration, the levels of AFP and DCP markedly decreased to 95 ng/ml and 0.0 AU/ml, respectively, and the lung metastases and tumor emboli disappeared. Moreover, there were no side-effects including liver dysfunction.

Administration, Oral↗
PubMed1992

Time course of hepatitis A virus antibody titer after active and passive immunization.

To investigate the antibody titer necessary to prevent hepatitis A virus infection, either 15 or 7.5 mg/kg of immune serum globulin was injected into 10 antihepatitis A virus negative volunteers and their serum antihepatitis A virus titers were observed for 28 wk. In addition, antibody titers were observed for 96 wk in a phase 1 clinical trial of a hepatitis A vaccine. The two studies were then compared to assess the immunogenicity of the vaccine and the persistence of the antibody. Serum-neutralizing antibody titers that were greater than or equal to 4 (considered as positive) persisted for 18 wk and 14 wk after the injection of 15 and 7.5 mg/kg of globulin, respectively. Hepatitis A virus vaccine recipients showed adequate neutralizing antibody titers, with the groups receiving 1, 0.5 and 0.25 micrograms/dose showing titers of 4(5.5), 4(4.7) and 4(4), respectively, at 18 mo after the third inoculation. These findings suggested that effective blood antibody titers were likely to be retained in the 1.0 micrograms or 0.5 micrograms/dose groups for at least several years. Moreover, the serum antihepatitis A virus titers demonstrated by a modified radioimmunoassay changed in parallel with the neutralizing antibody titers in the volunteers injected with globulin.

Adult↗
PubMed1992

Evaluation of three hepatitis C virus-related antibodies C100, KCL-163, JCC. Tests for screening blood donors.

To evaluate the most effective method for detecting hepatitis C virus (HCV) carriers in a large population of blood donors, HCV-related antibodies were measured in 919 donor serum samples using three different enzyme-linked immunosorbent assays. The antibodies were C100 and KCL-163, nonstructural proteins of HCV, as well as JCC, a translation product of the presumptive HCV core gene. Fourteen (1.5%), 12 (1.3%), and 13 (1.4%) specimens were positive for anti-C100, anti-KCL-163, and anti-JCC, respectively. HCV RNA was detected by the polymerase chain reaction in seven (25.0%) of the 28 specimens that were anti-HCV-positive by at least one of the three assays. Four of the seven specimens were detected by anti-C100 screening, while the remaining three were not. All seven specimens were positive for KCL-163 and/or JCC antibodies. These findings suggest that screening for both KCL-163 and JCC antibodies may be of particular use in accurately identifying HCV-positive blood.

Adult↗
PubMed1992

Clinical evaluation of three anti-HCV ELISAs in patients with various liver diseases.

We measured antibodies to hepatitis C virus (HCV) in 380 patients with various liver diseases by three enzyme-linked immunosorbent assays (ELISAs): HCV antibody ELISA test (C100), KCL-163 (KCL) corresponding to the nonstructural protein of HCV, and JCC based on the translation product of the presumptive HCV core gene. Of 233 cases of non-A, non-B (NANB) liver disease, 63.9% were anti-C100 positive, 69.1% were anti-KCL positive, and 79.8% were anti-JCC positive. Detection of serum HCV-RNA in 213 cases of chronic NANB liver disease revealed that the concordance was 80.3% for C100, 86.4% for KCL, 94.8% for JCC, and 95.3% for all three ELISAs. Overall, 85.4% of chronic NANB cases were considered to have type C disease with HCV infection. The most reliable assays for diagnosing chronic NANB liver disease as type C appeared to be the KCL and JCC ELISAs.

Adolescent↗
PubMed1992

Clinical trial of a lyophilized inactivated hepatitis A candidate vaccine in healthy adult volunteers.

The safety and immunogenicity of a lyophilized inactivated hepatitis A vaccine was tested in healthy adult male volunteers. Thirty-six volunteers, all of whom were negative for antibody to HAV (anti-HAV), were divided into three dosage groups, 1.0, 0.5 and 0.25 micrograms of viral protein, respectively. Each group received a total course of three intramuscular injections at months 0, 1 and 6. Slight side effects were noted after 16 of 99 injections and the occurrence and degree were almost identical to those of other commercial vaccines. On the other hand, all subjects had measurable titres of serum anti-HAV neutralizing antibodies as early as 2 months after the first injection. The mean values of serum anti-HAV neutralizing antibodies at 7 months in the 1.0, 0.5 and 0.25 micrograms dose groups were 64-, 12-, and 9-fold higher, respectively, than those observed at 5 days in five recipients given 7.5 mg kg-1 body weight of immune serum globulin (ISG).

Adolescent↗
PubMed1992

Determination of optimum cutoff levels of plasma des-gamma-carboxy prothrombin and serum alpha-fetoprotein for the diagnosis of hepatocellular carcinoma using receiver operating characteristic curves.

Optimum cutoff levels for plasma des-gamma-carboxy (abnormal) prothrombin (DCP) and serum alpha-fetoprotein (AFP) were determined by analyzing receiver operating characteristic (ROC) curves to discriminate between hepatocellular carcinoma (HCC) and benign hepatic conditions. Plasma DCP levels in 200 patients with HCC and 197 control patients with benign liver diseases were measured by an enzyme immunoassay with anti-DCP monoclonal antibodies, while serum AFP levels for both groups were measured by radioimmunoassay. From ROC curves and tangential lines with a slope of 1.0, the cutoff levels of DCP and AFP were determined to be 0.11 AU/ml and 150 ng/ml, respectively. Lowered cutoff levels of DCP did not improve the sensitivity, in contrast to the increased sensitivity obtained by lowering the specificity of AFP. The sensitivities and specificities determined in this study were close to the currently used values of 0.1 AU/ml for DCP and 200 ng/ml for AFP, justifying these cutoff levels for the differentiation of benign and malignant liver diseases.

Adolescent↗
PubMed1992

[Fundamental studies of hepatitis C virus: a review].

In 1974, Prince et al. reported the existence of posttransfusion hepatitis with a long incubation period which was not related to hepatitis B virus (HBV). These cases were named "non-A, non-B" (NANB) hepatitis. The genome of NANB hepatitis virus was discovered recently using a recombinant complementary DNA (cDNA) approach. It was termed the hepatitis C virus (HCV), and a specific diagnostic tool for the circulating HCV antibody (anti-HCV) was developed using a purified viral polypeptide derived from recombinant yeast expressing a small part of the HCV genome. HCV is believed to be the main cause of blood-borne non-A, non-B hepatitis worldwide, which frequently evolves to chronic hepatitis and cirrhosis, and which may also be involved in the development of hepatocellular carcinoma. HCV is classified as part of the flaviviridae family and contains a positive-stranded RNA molecule by approximately 10 kb nucleotides. The HCV genome encodes a large polyprotein precursor, which is processed in structural nucleocapsid and envelope proteins and in non-structural proteins (NS1-NS5). Nucleotide sequence comparisons of distinct HCV isolates have shown a significant genetic variability between the different HCV strains. At present the diagnosis of HCV infection depends on various anti-HCV tests including second generation HCV Ab. Antigenic markers for HCV are being developed but the concentrations of HCV antigens in serum are at the lower limit of detectability by existing immunoassay technology. A polymerase chain reaction has been used to detect HCV RNA in the serum and liver. Serum HCV RNA disappears from serum after effective IFN treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Genes, Viral↗
PubMed1992

Prevalence of hepatitis C virus antibodies in hemodialysis patients and dialysis staff.

To estimate the prevalence of hepatitis C virus (HCV) infection in dialysis patients, serum anti-HCV antibodies were evaluated in 489 Japanese patients undergoing hemodialysis, and 152 members of the hospital dialysis staff by enzyme-linked immunosorbent assays for anti-C100, anti-KCL-163 (HCV nonstructural protein), and anti-JCC (translation product of the presumptive HCV core gene). Of the 489 hemodialysis patients, 100 (20.4%) were positive for anti-C100, 107 (21.9%) for anti-KCL-163, and 168 cases (34.4%) for anti-JCC. These rates were significantly higher than those for either the hospital staff or the healthy blood donors. Forty-two per cent of the dialysis patients were anti-HCV positive by at least one assay, suggesting that HCV infection is more common among this population than previously thought. Positivity for anti-HCV was related to the duration of hemodialysis. Elevated alanine aminotransferase levels were present in 12.5% of the dialysis patients, 77% of whom were also anti-HCV positive. The positivity rates among the 152 members of the hospital staff were 0.7% for anti-C100, 2.6% for anti-KCL-163, and 8.6% for anti-JCC, with the anti-JCC rate of positivity exceeding that of the healthy blood donors.

Adult↗
PubMed1992

Two cases of accidental transmission of hepatitis C to medical staff.

Two medical doctors (a 38-year-old male and a 25-year-old female) were admitted to our department with jaundice. They had injured themselves with, respectively, a scalpel and a needle contaminated with anti-hepatitis C virus antibody-positive blood, at 2 and 1.5 months, respectively, prior to admission. They were both suffering from clinically typical acute hepatitis. The polymerase chain reaction showed that hepatitis C RNA and anti-hepatitis C virus antibody were transiently positive in the male doctor, while serum transaminase levels were transiently abnormal. In the female doctor, hepatitis C RNA was initially negative, but became strongly positive, and abnormal serum transaminase levels persisted. Interferon therapy resulted in the hepatitis C RNA's becoming negative again, and the transaminase levels returned to normal. The clinical and other findings strongly suggested that in both patients hepatitis C developed as a result of the respective in-hospital accidents.

Accidents, Occupational↗
PubMed1991

Clinical usefulness of des-gamma-carboxy prothrombin assay in early diagnosis of hepatocellular carcinoma.

Des-gamma-carboxy prothrombin (DCP) was evaluated as a serological marker for hepatocellular carcinoma (HCC), particularly in patients with early HCC. In 1192 patients with various diseases, plasma DCP levels were measured by a newly developed enzyme immunoassay method using an anti-DCP monoclonal antibody. Of the 254 patients with HCC, 143 (56%) had abnormal DCP levels of greater than 0.1 AU/ml. In contrast, elevated DCP levels were rarely observed in patients with chronic hepatitis, liver cirrhosis, metastatic liver cancer, and other malignant tumors. Because no correlation was observed between DCP and alpha-fetoprotein (AFP), the combined measurement of these two complementary markers appears to be useful in the diagnosis of HCC. Since normal levels were observed in 29 of 30 patients (97%) with small liver tumors measuring 2 cm or less in diameter, the diagnostic application of the DCP assay to small liver tumors is limited. However, in patients with tumors larger than 2 cm, the plasma DCP assay may even be more useful than AFP. Among 46 patients with liver cirrhosis or chronic hepatitis who subsequently developed HCC, significantly increased DCP and AFP levels were observed in nine patients (20%) and 14 patients (30%), respectively, when a tumor was detected. When the results of both assays were combined, 19 patients (41%) had elevated levels of one or both markers. Although the plasma DCP assay alone is not sensitive enough to detect early small liver cancers, it could be applied as a complementary tumor marker together with AFP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗