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Biomedical subjects

S Mishiro

Publications and source records attributed to S Mishiro.

At least 91 records · Page 5Linked to original sources
PubMed1990

Non-A, non-B hepatitis specific antibodies directed at host-derived epitope: implication for an autoimmune process.

A cDNA clone (GOR47-1) bearing an epitope with an aminoacid sequence GRRGQKAKSNPNRPL (GOR epitope) was isolated from the plasma of a laboratory chimpanzee infected with human non-A, non-B hepatitis (NANBH) agent. The epitope was not encoded by reported sequences of hepatitis C virus (HCV) but instead was coded for by a host cellular sequence. An enzyme-linked immunosorbent assay (ELISA) was developed for antibodies to the GOR epitope (anti-GOR). A patient with acute NANBH produced both IgM and IgG classes of anti-GOR in the acute phase of the illness, with concentrations of IgG class anti-GOR rising when anti-HCV became detectable. Anti-GOR was detected in serum from 59 (81%) of 73 patients with chronic NANBH, 40 (65%) of 62 with NANB liver cirrhosis, and 25 (63%) of 40 NANB patients with primary hepatocellular carcinoma, but in only less than 10% of patients with chronic liver diseases due to hepatitis B virus, alcohol, or an autoimmune disorder, and in only 2% of voluntary blood donors. Circulating HCV-RNA was detected by polymerase chain reaction (PCR) in most patients seropositive for anti-GOR but negative for anti-HCV. Detection of anti-GOR would therefore help in the diagnosis of NANBH and in reducing the occurrence of post-transfusion hepatitis.

Amino Acid Sequence↗
PubMed1990

Detection of hepatitis C virus RNA by a two-stage polymerase chain reaction with two pairs of primers deduced from the 5'-noncoding region.

The 5'-noncoding region of hepatitis C virus (HCV) genomes is highly conserved. A two-stage polymerase chain reaction (PCR), involving two pairs of primers deduced from the 5'-noncoding region of the HCV genome, was developed for a sensitive and specific detection of HCV RNA. The first stage of PCR was performed for 35 cycles with primers capable of multiplying fragments of 221 base pairs. PCR products in samples negative for HCV RNA were subjected to the second stage of PCR for 30 cycles with primers located internal to those employed in the first stage of PCR. The two-stage PCR detected up to 10 chimpanzee infectious doses/ml of HCV, and HCV RNA in 11 (92%) of 12 sera from patients with chronic non-A, non-B hepatitis without detectable antibodies to HCV by a commercial assay kit. Primers from the 5'-noncoding region of the HCV genome would be suitable for detecting HCV RNA by PCR, since the other regions of the HCV genome diverge extensively in sequence because of its nature as an RNA virus.

Animals↗
PubMed1988

Glucagon and insulin for the treatment of hepatic failure in dimethylnitrosamine-intoxicated rats.

When rats received dimethylnitrosamine every 24 h until death, plus hormone treatment after the first 24 h, the survival was enhanced between 100 and 140 h compared with the control rats, with attenuated derangements of prothrombin time and serum albumin levels at 120 h. In rats given a single dose of dimethylnitrosamine, hepatic DNA synthesis peaked at 48 h. The synthesis was increased after hormone treatment when started immediately, but not when delayed for 24 h. Hormone treatment for 3 days starting 24 h after a single dose of dimethylnitrosamine produced a rapid normalization of decreased hepatic protein content on day 9, although hepatic DNA content was not affected. These results suggest that this treatment is effective for hepatic failure, and the promotion of restoration of liver function is a contributing factor to its effect, in addition to the stimulation of hepatocyte proliferation.

Animals↗
PubMed1986

Large hepatitis B surface antigen polypeptides of Dane particles with the receptor for polymerized human serum albumin.

Large hepatitis B surface antigen polypeptides with apparent molecular sizes of 39,000 and 43,000 daltons (P39 and P43) were liberated from a purified preparation of Dane particles of subtype adr. They were tested for reactivity with monoclonal antibodies raised against three synthetic oligopeptides representing fundamental sequences of the pre-S region in deoxyribonucleic acid of hepatitis B virus (subtype adr), as well as with monoclonal antibody against the major surface antigen polypeptide (P22) coded for by the S gene. Both P39 and its glycosylated form P43 bound to all four monoclonal antibodies, thereby indicating that they were coded for by the sequence of 1200 nucleotides, from the second ATG codon in the pre-S region to the stop codon of the S gene. Both P39 and P43 bound to polymerized human and chimpanzee albumins, but not to polymerized albumin from species without susceptibility to hepatitis B virus. Due to their presence in Dane particles and the expression of a polyalbumin receptor, the immune responses against P39 and P43 may have significance in infection with hepatitis B virus and its immunoprophylaxis.

Antibodies, Monoclonal↗
PubMed1986

A synthetic peptide vaccine involving the product of the pre-S(2) region of hepatitis B virus DNA: protective efficacy in chimpanzees.

The S gene encoding the major surface polypeptide of hepatitis B virus is preceded by the region pre-S(2) with a capacity to code for 55 amino acid residues. In the product of region pre-S(2), the sequence of 19 amino acid residues (amino acids 14-32 from the N terminus) representing an area of high local hydrophilicity is shared by viral strains of subtypes adr, ayw, and ayr; residue 22, phenylalanine, is replaced by leucine in a strain of the other subtype, adw. A synthetic peptide vaccine involving these 19 amino acid residues, when given to two chimpanzees, raised antibodies that bound to viral particles and protected the animals from challenge with 10(6) chimpanzee infectious doses of hepatitis B virus.

Animals↗
PubMed1986

Integration of region X of hepatitis B virus genome in human primary hepatocellular carcinomas propagated in nude mice.

Tissues of human primary hepatocellular carcinoma (PHC) from six patients infected with hepatitis B virus (HBV) were propagated in nude mice, as well as a strain of hepatitis B surface antigen-positive PHC (PLC/PRF/5). Integration of viral DNA into chromosomal DNA of tumour cells was evaluated by the capacity to hybridize with radiolabelled DNA probes, each representing fundamental parts of the HBV genome, that is S and C genes and regions pre-S and X. All PHC cells possessed region X integrated in their chromosomes. However, integration of the S gene, C gene and region pre-S was found in only six of the seven PHCs. Based on these findings, the integration of region X seems to be most closely associated with carcinogenesis in HBV infection.

Animals↗
PubMed1985

Hemagglutination assay of polypeptide coded by the pre-S region of hepatitis B virus DNA with monoclonal antibody: correlation of pre-S polypeptide with the receptor for polymerized human serum albumin in serums containing hepatitis B antigens.

The receptor for polymerized human as well as chimpanzee serum albumins has been identified on the 55-amino acid polypeptide coded by the pre-S region of hepatitis B virus DNA. Monoclonal antibodies were raised against a synthetic polypeptide of 19 amino acid residues representing a hydrophilic region of the pre-S amino acid sequence deduced from hepatitis B virus DNA. Sheep erythrocytes fixed with glutaraldehyde were coated with monoclonal antibody against the synthetic polypeptide to develop a hemagglutination assay for pre-S polypeptide. The pre-S polypeptide was detected in the serum containing hepatitis B surface antigen particles along with hepatitis B e antigen, with titers in parallel with those of the receptor for polymerized human serum albumin.

Animals↗
PubMed1983

Decrease in the zinc turbidity test values in patients with liver cirrhosis: a possible indicator for impending hepatocellular carcinoma.

A retrospective investigation of 21 cases of hepatocellular carcinoma with liver cirrhosis presumably of viral origin revealed a significant fall in the value of the zinc turbidity test from 15.5 +/- 6.9 (mean +/- SD) at 1 year to 11.2 +/- 2.5 units at 6 months before the discovery of the carcinoma (p less than 0.05), and a return to 16.8 +/- 7.2 units one month after the diagnosis (p less than 0.05). The values at 6, 2 and 1 month before the diagnosis were significantly lower than that for 120 control cirrhotics without hepatocellular carcinoma at 16.3 +/- 7.2 units (p less than 0.05). The fall in value occurred before or concurrently with a rise in the alpha-fetoprotein level in three patients, in whom it has been determined serially. Based on the results obtained, the decrease in the zinc turbidity test value may be used as an indicator for impending hepatocellular carcinoma in patients with liver cirrhosis.

Adult↗
PubMed1981

Tubular forms of hepatitis B surface antigen bind with the nucleus of 22-nm spherical HBsAg particles.

Spherical hepatitis B surface antigen particles (HbsAg) of 22-nm diameter were treated with sodium dodecylsulphate in the absence of reducing agents, and their nuclei were exposed. Factors that interact with the nucleus of HbsAg were detected in the serum of HBsAg carriers who were seropositive for hepatitis B e antigen and identified as tubular forms of HBsAg. The other categories of hepatitis B antigen, Dane particles, and 22-nm spherical HBsAg did not bind with the nucleus of HBsAg. When tubular forms of HBsAg had been treated with a proteolytic enzyme, they lost the reactivity to bind with the nucleus of HBsAg. On the basis of the results obtained, tubular forms of HBsAg bear the receptor of protein nature for the nucleus of 22-nm spherical HBsAg. The receptor allows rapid determination of tubular forms by a haemagglutination method for the evaluation of their clinical and epidemiological implications.

Carrier State↗
PubMed1980

Hepatitis B e antigen polypeptides isolated from sera of individuals infected with hepatitis B virus: comparison with HBeAg polypeptide derived from Dane particles.

Hepatitis B e antigen (HBeAg) occurs in the serum of individuals infected with hepatitis B virus both free and in association with IgG. Utilizing a succession of steps involving salt precipitation, affinity chromatography, ion-exchange chromatography and isoelectrofocusing, we isolated free and IgG-bound forms of HBeAg from the sera of infected individuals with an overall gain in specific activity of 3000-fold and 540-fold, respectively. Polypeptide profiles of purified HBeAg preparations were studied by SDS-polyacrylamide gel electrophoresis in the presence of 2-mercaptoethanol. Both free and IgG-bound preparations revealed polypeptides with mol. wt. of 15500 (P15.5) and 16 500 (P16.5), and HBeAg activity was detected corresponding to their positions. The HBeAg polypeptides (P15.5/16.5) derived from sera were physicochemically different from the two polypeptides with HBeAg activity (P19 and P45) liberated from Dane particle cores by the conventional method involving incubation with Nonidet P40 and 2-mercaptoethanol. However, when core particles were prepared in the presence of a proteolytic enzyme, in addition to Nonidet P40 and 2-mercaptoethanol, they gave rise to HBeAg polypeptides with mol. wt. of 31000 (P31) and 15 500. Furthermore, P31 split into P15.5 when heated at 100 degrees C for 2 min. On the basis of these results, P15.5 may be assumed to be the essential polypeptide bearing HBeAg activity in the serum and also in Dane particles.

Hepatitis B↗
PubMed1980

A 49,000-dalton polypeptide bearing all antigenic determinants and full immunogenicity of 22-nm hepatitis B surface antigen particles.

Spherical 22-nm hepatitis B surface antigen (HBsAg) particles with a subtype adr were purified from plasma of asymptomatic carriers of hepatitis B virus. When purified HBsAg preparation was treated with sodium dodecylsulfate in the absence of reducing agents, it yielded spherical particles with a diameter smaller than 22 nm, and in addition, a polypeptide with a molecular size of 49,000 daltons, which seemed to constitute the outer coat of HBsAg particles. The recovery of the polypeptide on the basis of optical density at 280 nm was 2%, starting from 22-nm HBsAg particles. The 49,000-dalton polypeptide apparently represented a structural unit of the surface of HBsAg particles, since it bore all common (a, Re) and subtypic (d, r) determinants with essentially the same antigenic titers as intact HBsAg particles. Furthermore, this polypeptide was equally immunogenic as 22-nm HBsAg particles in raising corresponding antibodies in mice. When the 49,000-dalton polypeptide was reduced in the presence of 2-mercaptoethanol, it cleaved into 22,000- and 27,000-dalton polypeptides with a drastic decrease in both antigenicity and immunogenicity. These results indicate the different molecular arrangements between outer coat and inner portion of HBsAg particles, and a potential application of the 49,000-dalton polypeptide as a component vaccine, owing to its strong antigenicity both in vitro and in vivo.

Animals↗
PubMed1979

Shift from free "small" hepatitis B e antigen to IgG-bound "large" form in the circulation of human beings and a chimpanzee acutely infected with hepatitis B virus.

Hepatitis B e antigen (HBeAg) occurs both free and in association with IgG in the circulation of individuals infected with hepatitis B virus (HBV). We determined free and IgG-bound HBeAg forms separately in the serum of humans and a chimpanzee acutely infected with HBV. In a patient with laboratory acquired HBV infection, the proportion of free HBeAg gradually decreased from 89% to 23%. A similar shift from free to IgG-bound form of HBeAg was invariably observed in 5 additional patients with acute Type B hepatitis. In a chimpanzee that had been experimentally inoculated with HBV, free HBeAg appeared first, then gradually and completely shifted to the IgG-bound form. Finally, IgG-bound HBeAg disappeared, and antibody to HBeAg was detectable in the serum. The determination of both free and IgG-bound forms of HBeAg may provide valuable information, because their ratio reflects the stage and prognosis of acute HBV infection.

Acute Disease↗
PubMedDate not supplied

Decreased collagen accumulation by a prolyl hydroxylase inhibitor in pig serum-induced fibrotic rat liver.

Hepatic fibrosis was induced in rats by repeated i.p. injections of pig serum. The hepatic hydroxyproline content increased to 2.1 times the normal control level at 6 weeks and to 3.2 times at 10 weeks. When P-1894B, an inhibitor of prolyl hydroxylase, was administered, there was a dose-dependent inhibition of the increase to nearly normal control levels at 6 and 10 weeks. There was also by histology a dose-dependent reduction in the degree of hepatic fibrosis. Hepatocellular damage was minimal and its extent did not vary with the degree of fibrosis or the treatment. P-1894B dose dependently reduced the hydroxylation of peptidyl proline in the fibrotic liver. These data suggest that P-1894B inhibited hepatic fibrogenesis by direct action on collagen but not by protection against hepatocellular damage leading to collagen formation. A prolyl hydroxylase inhibitor may be a candidate for use in treatment of hepatic fibrosis.

Animals↗