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Biomedical subjects

T Shikata

Publications and source records attributed to T Shikata.

At least 109 records · Page 6Linked to original sources
PubMed1988

Enzyme-altered liver cell foci in woodchucks infected with woodchuck hepatitis virus.

The histochemical characteristics of liver cell foci in woodchucks were investigated. The foci appeared to be distributed throughout the liver and were observed only in the woodchuck hepatitis virus (WHV)-positive animals, including all 19 woodchucks with hepatocellular carcinoma(HCC), and 7 without HCC. No foci appeared in 11 WHV-negative animals. Histochemical studies revealed that liver cell foci and carcinoma cells were characterized by positive gamma-glutamyl transpeptidase (GGT) enzymatic reactions and decreased glucose-6-phosphatase enzyme activity compared to non-neoplastic liver. Furthermore, serum GGT was significantly elevated in almost all of the animals which had larger carcinomas. Ultrastructural findings of foci showed some resemblance to carcinoma cells, being characterized by abundant free ribosomes within the cytoplasm and undeveloped endoplasmic reticulum. These results suggest that the liver cell foci are potential precursors of HCC in WHV-infected animals, and that serum GGT may be a useful marker for indicating the development of carcinoma.

Animals↗
PubMed1987

Histopathological analysis of chronic hepatitis B virus (HBV) infection in relation to HBV replication.

The interrelationship among expression patterns of hepatitis B surface and core antigens (HBsAg and HBcAg) in the liver, hepatitis B virus (HBV) DNA in sera, HBeAg/anti-HBe status and histological features was examined in 189 liver specimens and 106 sera from Japanese patients with chronic HBV infection, utilizing immunoperoxidase methods and a spot hybridization technique. HBsAg and HBcAg were distributed uniformly among the lobules in 8 viral carriers with "normal" liver (NVC) and 30 patients with persistent hepatitis (PB) seropositive for HBcAg. This uniform staining pattern was quite distinct from the non-uniform and irregular patterns in 137 patients with chronic active hepatitis (CAH) associated with or not associated with cirrhosis. HBcAg was often found to be stained strongly in the cytoplasm as well as in the nucleus of hepatocytes in HBeAg-positive CAH, in contrast to NVC/PH, in which cytoplasmic HBcAg was very weak. Serum HBV DNA was detected in all 22 cases with HBeAg-positive NVC/PH, 41 of 46 (89.1%) cases with HBeAg-positive CAH, 6 of 23 (26.1%) casew with anti-HBe-positive CAH and none of 3 cases with anti-HBe-positive NVC/PH. The level of serum HBV DNA and staining of HBcAg were in decreasing order in these groups. While the presence of serum HBV DNA and HBcAg staining was always associated with HBeAg seropositivity in NVC/PH, this was not always found in CAH. Moreover, necroinflammatory activity in the liver did not always parallel viral replication in CAH. These findings seem to confirm that NVC/PH and CAH have different biologic processes; viral replication is always concordant in the former, but is sometimes discordant in the latter with HBeAg/anti-HBe status. The immunologic response of the host seems to suppress and distort replication of the virus to a varying degree among patients and areas of the same liver in CAH differently to that in NVC/PH. The different life cycle of the virus, including integration of viral DNA into the cellular genome, may subsequently result in discordant states of various virus markers in CAH.

DNA Replication↗
PubMed1987

The characteristics of alcoholic liver disease in Japan. Clinicopathologic comparison with alcoholic liver disease in the United States.

Alcoholic liver disease (ALD) in Japan was compared clinicopathologically with the occurrence in the U.S.A. ALD found in Japan was more frequently complicated by other hepatic diseases including non-A, non-B chronic hepatitis than ALD found in the U.S.A. (9.9% versus 21.9%). Patients with such complications were excluded from this study. The chief complaints of the total of 51 alcoholics studied in the U.S.A. were abdominal distension or jaundice and those of 98 alcoholics studied in Japan were non-specific: general fatigue, weakness or appetite loss. The U.S. patients exhibited more elevated levels of serum bilirubin (8.1 +/- 7.5 versus 1.9 +/- 2.4 mg/dl, mean +/- SD) and a higher incidence of leukocytosis (49.0% versus 5.1%). While the serum glutamic-oxalacetic transaminase (GOT) levels were not significantly different between the two groups (146.5 +/- 116.8 versus 140.8 +/- 147.7 IU/L), the serum glutamic-pyruvic transaminase (GPT) levels among Japanese alcoholics were higher (38.6 +/- 31.4 versus 87.4 +/- 99.1 IU/L) and in about one quarter of these patients, serum GPT was higher than serum GOT, a feature not seen in the patients in the U.S.A. Comparative histopathologic study of 337 U.S. patients and 210 Japanese patients disclosed a higher frequency of cirrhosis (46.9% versus 33.8%), the presence of Mallory bodies (58.5% versus 13.8%) and marked neutrophilic exudation (45.1% versus 6.2%). Thus, the majority of Japanese alcoholics exhibited progression of liver disease, eventually leading to cirrhosis, due to hepatocellular drop-out and fibrosis caused by a mechanism different from alcoholic hepatitis. In addition, ALD in the U.S.A. revealed more striking extension of fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Relation between non-A, non-B and delta hepatitis: studies with monoclonal antibodies.

To further investigate the specificity of the monoclonal antibodies (48-1 and S-1) associated with NANB hepatitis, extensive IF studies were carried out on liver biopsy specimens from chimpanzees with experimental hepatitis A, B, NANB, or D, or from normal chimpanzees. Both 48-1 and S-1 antibodies reacted in the same manner with liver biopsy specimens from 47 of 50 (94%) chimpanzees with acute or chronic NANB hepatitis and 15 of 18 (83%) chimpanzees with type D hepatitis. Examinations of serial liver biopsy specimens revealed that the duration of expression of the antigen reacting with the antibodies in hepatocytes of chimpanzees infected with NANBV appeared to be longer than that of chimpanzees infected with HDV. By thin section EM, the presence of the microtubular aggregates, identical to those previously described for chimpanzees with NANB hepatitis and shown by immuno EM to react with the antibodies, was noted in hepatocytes during the acute phase of hepatitis D. The antibodies did not react with liver biopsy specimens from chimpanzees acutely or chronically infected with HBV, or HAV, or from normal chimpanzees. The present results confirm our previous observations with the 48-1 and S-1 antibodies. Furthermore, the finding that these two antibodies were also associated with hepatitis D would support the possibility that NANB agents and the HDV may have a similar nature or may elicit a similar host response.

Animals↗
PubMed1986

Detection of an antigen (AN6520), possibly related to non-A, non-B hepatitis, by monoclonal antibodies. I.

The antibody to AN6520 antigen, which was isolated from the liver of a patient with non-A, non-B hepatitis (NANBH), has been detected frequently in convalescent sera from patients with NANBH by the passive hemagglutination (PHA) test. In a further study, we established hybridoma cells secreting antibodies against AN6520 antigen and obtained ascitic fluids with PHA titers ranging from 1:10(5) to 1:10(7). In immunodiffusion with AN6520 antigen, all monoclonal antibodies were found to form an identical precipitin line. These lines were also identical to those formed by rabbit antiserum against AN6520 antigen and by convalescent sera from patients with NANBH. With one of the monoclonal antibodies, 1-F12, solid-phase radioimmunoassay (SP-RIA) for detecting AN6520 antigen was developed as well as blocking RIA for anti-AN6520 antibody detection. The antigen assay was 50 times more sensitive than the reverse passive hemagglutination (R-PHA) test, with a sensitivity threshold of the 1 ng/ml of antigen solution; the antibody assay was 10 times more sensitive than PHA. The results with this blocking RIA were mostly in agreement with the data obtained by PHA. Furthermore, the antigen in human sera, which had never been detected by R-PHA test, could be detected by SP-RIA.

Aged↗
PubMed1986

Non-A, non-B hepatitis related AN6520 Ag is a normal cellular protein mainly expressed in liver. II.

Detection of AN6520 Ag/Ab in human sera had indicated a close association with non-A, non-B hepatitis (NANBH). In this study, we investigated the immunochemical nature of AN6520 Ag and measured the amounts in various human and chimpanzee organs in order to clarify the association with NANBH. AN6520 Ag was found to be composed of polypeptide(s) with an apparent molecular weight of 45,000 daltons (45 kD), which are noncovalently linked together. Human antibodies in convalescent sera from NANBH patients as well as monoclonal antibodies were found to recognize only the high-order structure of the antigen, whereas rabbit antibody recognized both the high-order structure and the reduced form of 45 kD polypeptide(s). AN6520 Ag could be detected in most of the livers tested including those without any liver damage and fetal livers; their amounts varied considerably from each other. The antigen could be detected also in organs other than liver, but in contrast to liver, the amounts were small and did not vary as much between individuals. From the data of immunoblotting using rabbit antibody, our observed variation of antigen content in liver was considered to be due to the difference in expression of 45 kD polypeptide(s). Although no specific relationship was found between the amount of the antigen in liver and NANBH, the antigen was found to increase several times in livers of chimpanzees after the inoculation of NANBH virus. These data suggest that AN6520 Ag is a normal cellular protein existing mainly in liver and that its quantity may vary under some conditions such as NANBH.

Adult↗
PubMed1986

Immunoperoxidase investigation of Regan isoenzyme of alkaline phosphatase in maxillary sinus carcinomas.

The Regan isoenzyme of alkaline phosphatase is known to be produced ectopically by various malignant tumors. To assess whether this isoenzyme is expressed in maxillary sinus carcinomas, immunostaining for Regan isoenzyme was carried out on 35 maxillary sinus carcinomas comprising 27 squamous cell carcinomas, 6 adenocarcinomas, and 2 adenoid cystic carcinomas. The enzyme was shown to be present in 11 of 27 cases of squamous cell carcinoma, 2 of 6 cases of adenocarcinoma, and 1 of 2 cases of adenoid cystic carcinoma. Regan isoenzyme was identified in the cytoplasm and/or cell membrane of squamous cell carcinoma cells, whereas it was demonstrated mainly on the luminal membrane and in the secretions of both adenocarcinoma and adenoid cystic carcinoma cells. These findings show that Regan isoenzyme does, indeed, occur in maxillary sinus carcinomas.

Adenocarcinoma↗
PubMed1986

Liver morphology in marmosets infected with epidemic non-A, non-B hepatitis in India.

In this study the morphological changes in the livers of marmosets inoculated with stool extracts from epidemic non-A, non-B hepatitis patients in India were examined. The histologic changes of epidemic non-A, non-B hepatitis in marmosets consisted mainly of round cell infiltration in the portal tracts, spotty liver cell necrosis, sinusoidal lymphocyte infiltration, and Kupffer cell mobilization. By electron microscopy, liver cells from infected marmosets showed cisternal dilation of the endoplasmic reticulum, irregularly-shaped nucleus, and disorganization of the mitochondrial cristae. In some areas interaction of lymphocytes with hepatocytes was observed. Similar observations have been made in type B hepatitis infection, presumably due to liver cell damage mediated by immune mechanisms. The result of our study is also compatible with the interpretation that the liver cell damage in this experimental model may be mediated by immune mechanisms.

Animals↗
PubMed1986

Safety and efficacy of hepatitis B vaccine in hospital personnel.

Clinical trials of the hepatitis B vaccine developed in Japan were performed by the phase I, phase II and phase III studies. It was found that this vaccine did not only contained HBV itself but also other pathogens. It was ascertained to be adequately safe, since no major side effect was induced. After inoculation of the vaccine 3 times into 195 hospital employees, an HBs antibody seroconversion rate of 91.8% (97.0% in females and 86.3% in males) was obtained. In recipients aged more than 50 years, the rate was significantly lower. Although 8.2% of the recipients were non-responders to the vaccination, there was no significant correlation between the strength of the HBs antibody response and the lymphocyte subsets in the peripheral blood. It was observed, however, that among the non-responders, the incidence of low OKT4+/OKT8+ cell ratios tended to be somewhat increased. In follow-up studies of the antibody, majority of subjects, in whom the antibody level at 1 month after the 3 inoculations was below 50 RIA units, demonstrated negative conversion within 1 or 2 years. Namely, their value were reduced to below the minimal protective antibody value for prophylaxis of HBV infection.

Adult↗