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Biomedical subjects

F Tsuda

Publications and source records attributed to F Tsuda.

At least 145 records · Page 8Linked to original sources
PubMed1986

Nucleotide sequence of a cloned hepatitis B virus genome, subtype ayr: comparison with genomes of the other three subtypes.

The entire nucleotide sequence of genomic DNA was determined for hepatitis B virus (HBV) of subtype ayr, which had been derived from the blood of a Japanese asymptomatic carrier. The genome was 3215 nucleotides long, and differed in DNA sequence by 10% from that of subtypes adw or ayw, but by only 2% from that of subtype adr. Amino acid sequences coded for by the S, C, P and X genes, as well as by the pre-S region, closely resembled those of subtype adr, indicating that the evolution of HBV/ayr from HBV/adr was more recent than the differentiation of the other three subtypes. In the product of the S gene, the mutually exclusive subtypic determinants of the surface antigen, d and y, were associated with variation of amino acid residues at only the 68th and 122nd positions from the N terminus, in contrast to the variation at as many as seven positions for the other set of subtypic determinants, w and r. Sequences representing high local hydrophilicity in the product of the S gene were involved in subtypic variation, although such sequences in the pre-S region were shared by HBV genomes of the various subtypes. In particular, a hydrophilic sequence of 19 amino acid residues, coded for by the pre-S(2) region and implicated in the presumed hepatotropism of HBV, was possessed in common by HBV/adr, HBV/ayr and HBV/ayw, and differed in HBV/adw by only one residue at the 9th position. This amino acid sequence appears to be a promising candidate for a synthetic peptide vaccine.

Amino Acid Sequence↗
PubMed1986

Translation products of pre-S(1), pre-S(2) regions and the S gene of hepatitis B virus: susceptibility of their antigenic activities to treatment with heat, urea, formalin or pepsin.

Hepatitis B subviral particles, purified from plasma of asymptomatic carriers seropositive for hepatitis B e antigen, were treated with various conditions reported for the processing of vaccines. Thereafter, antigenic activities displayed by the translation products of pre-S(1), pre-(2) regions and the S gene were determined with monoclonal antibodies, and the reactivity for polyalbumin receptor was tested. Heating at 100 degrees C for 1.5 min and then at 65 degrees C for 10 h preserved more than 1/2 of antigenic activities representing products of pre-S(1), pre-S(2) regions and the S gene. After incubation in the presence of 8 M urea at 37 degrees C for 4 h, more than 2/3 of antigenic activities still remained. The antigenic activity of the S gene product was decreased to 2/3 and that of pre-S(2) region product to 1/3, after treatment with formalin at the final concentration of 1:4000 at 37 degrees C for 72 h, whereas the activity of pre-S(1) region product was affected drastically. Although 1/5 of the antigenic activity of the S gene product survived the digestion with pepsin for 18 h, antigenic activities of pre-S(1) and pre-S(2) region products were destroyed almost completely. Polyalbumin receptor, borne by the pre-S(2) region product, was lost by pepsin digestion also. Based on the results obtained, heating may be most appropriate for sterilizing plasma-derived hepatitis B particles for use as a vaccine, because it is reliably virucidal and would not affect the protective efficacy to an extent as the other virucidal methods would.

Epitopes↗
PubMed1986

Small and large forms of hepatitis B e antigen in the serum: determination by two-site sandwich radioimmunoassay with monoclonal antibodies.

Serum samples containing hepatitis B e antigen (HBeAg) were subjected to electrophoresis in agarose, and fast-migrating 'small' HBeAg and slow-migrating 'large' IgG-associated HBeAg were pooled separately. HBeAg of each category was determined by a two-site radioimmunoassay that sandwiched HBeAg between monoclonal antibody (anti-HBe) against one epitope of HBeAg, fixed on a solid support, and anti-HBe against another epitope, labelled with radioiodine. Eighteen sera in which small HBeAg dominated revealed activities of hepatitis B surface antigen-associated DNA polymerase significantly higher than 14 sera in which large HBeAg dominated (logarithm of ct/min, mean +/- s.e. 3.36 +/- 0.08 versus 2.14 +/- 0.11, P less than 0.01). Shift from small HBeAg to large HBeAg was observed, along with the disappearance of DNA polymerase, in the serum from two carriers who seroconverted to anti-HBe.

Antibodies, Monoclonal↗
PubMed1985

Immunoglobulin A antibody against hepatitis B core antigen in the acute and persistent infection with hepatitis B virus.

Antibody to hepatitis B core antigen of immunoglobulin A class was determined in the serum of patients infected with hepatitis B virus by a sandwich-type solid-phase radioimmunoassay with monoclonal antibodies. The antibody, as defined by a sample to normal ratio greater than 2.1, was detected in all of 39 patients with acute hepatitis, with titers varying widely depending on the time of blood sampling. In persons with persistent infection, the antibody was detected in only 2 (4%) of 46 asymptomatic carriers of the virus, contrasting with the positivity in as many as 15 (41%) of 37 patients with chronic persistent hepatitis, in 45 (94%) of 48 patients with chronic active hepatitis, and in 40 (87%) of 46 patients with liver cirrhosis with or without hepatocellular carcinoma. The mean +/- SE titer of antibody in chronic persistent hepatitis (3.8 +/- 0.9) was significantly lower than those in chronic active hepatitis (13.8 +/- 3.2) and cirrhosis with or without carcinoma (25.6 +/- 6.1) (p less than 0.001). Based on the results obtained, the antibody may reflect hepatic injury in the persistent hepatitis B virus infection.

Antibodies, Monoclonal↗
PubMed1985

Factors influencing postexposure immunoprophylaxis of hepatitis B virus infection with hepatitis B immune globulin. High deoxyribonucleic acid polymerase activity in the inocula of unsuccessful cases.

Hepatitis B immune globulin was given intramuscularly to 102 staff members of a dialysis unit within 48 h after the accidental needlestick exposure to blood containing hepatitis B surface antigen (HBsAg). Hepatitis B virus (HBV) infection developed in 11 of 56 persons (20%) who had been exposed to blood containing hepatitis B e antigen (HBeAg). Among 56 HBeAg-positive inocula, HBsAg-associated deoxyribonucleic acid polymerase activity in the 11 inocula that transmitted HBV infection was significantly higher than that in the remaining 45 inocula that did not (log counts per minute 3.27 +/- 0.57 vs. 2.09 +/- 1.19, p less than 0.001). These 11 HBeAg-positive inocula revealed higher hemagglutination titers of HBsAg (geometric mean 13.5 +/- 1.4 vs. 11.2 +/- 3.2, p less than 0.001). The receptor for polymerized human serum albumin was detected significantly more often in the inocula that transmitted HBV infection than those that did not (10/11 vs. 24/45, p less than 0.05). Based on the results obtained, the failure in protecting all of those exposed to HBeAg-positive blood would be attributable to a high concentration of HBV in some HBeAg-positive inocula and the inability of intramuscular injection to raise a protective level of antibody in the circulation immediately.

DNA-Directed DNA Polymerase↗
PubMed1984

Incidences of HBeAg and anti-HBe in, and clinical course of hepatitis B virus carriers.

A total of 336 hepatitis B virus (HBV) carriers were followed for more than 3 years with serial measurements of serological markers of HBV to determine the correlation between their clinical course and the HBeAg-anti-HBe system. In all, 139 had hepatitis B e antigen (HBeAg) at the beginning of the study. During the study, 30 of 139 HBeAg-positive carriers became HBeAg negative and subsequently gave a positive reaction for antibody to HBeAg (anti-HBe). The rate of seroconversion was 3.6% per year. Two types of profile of seroconversion were observed, rapid and gradual. No significant differences were observed in the incidences of HBeAg and anti-HBe in HBV carriers with or without liver cirrhosis (LC) and hepatocellular carcinoma (HCC). These findings do not support the report by Chung et al. (1983, J. Med. Virol. 11: 99-104) that a prolonged replicative phase of chronic HBV infection is essential for the occurrence of HCC. Two HBV carriers were diagnosed as having HCC at the time of seroconversion from HBeAg to anti-HBe. This finding supports the reports by Coursaget et al. (1978, J. Clin. Microbiol. 7: 394-395) and Musca et al. (1983, Hepatogastroenterology 30: 3-5) that actively replicating HBV sometimes becomes defective during the course of malignant transformation.

Adolescent↗
PubMed1984

Low molecular weight (7s) immunoglobulin M antibody against hepatitis B core antigen in the serum for differentiating acute from persistent hepatitis B virus infection.

Sera from persons infected with hepatitis B virus were fractionated into 19s and 7s moieties by high performance liquid chromatography and then tested for the antibody to hepatitis B core antigen (anti-HBc) of immunoglobulin M (IgM) class by radioimmunoassay. Sera from 17 patients with acute or fulminant hepatitis invariably showed a high activity of 19s IgM anti-HBc (sample/normal ratio 30.6 +/- 13.6). In addition, they all revealed a much lower activity of 7s IgM anti-HBc (4.1 +/- 3.4). In remarkable contrast, 7s IgM anti-HBc activity was higher than 19s IgM anti-HBc activity in the sera from 5 asymptomatic carriers (10.4 +/- 2.4 vs. 1.0 +/- 0.1), 4 patients with chronic persistent hepatitis (11.7 +/- 1.4 vs. 2.1 +/- 1.4), 13 with chronic active hepatitis (13.6 +/- 3.0 vs. 6.0 +/- 5.6), and 10 with liver cirrhosis (8.9 +/- 3.4 vs. 5.4 +/- 2.4). Among these 32 cases of persistent hepatitis B virus infection, there were only 2 (6.3%) in which the 7s IgM anti-HBc was lower than the 19s IgM anti-HBc. The proportion of patients who showed the value of 7s IgM anti-HBc exceeding that of 19s IgM anti-HBc was significantly higher for persistent (30 of 32) than for acute (0 of 17) hepatitis B virus infection (p less than 0.001). On the basis of these results, the determination of IgM anti-HBc in terms of 19s and 7s subpopulations would be useful for differentiating acute from chronic hepatitis B virus infection, especially when the titer of IgM anti-HBc is not high enough to exclude a persistent hepatitis B virus infection.

Acute Disease↗
PubMed1983

Immunoglobulin M antibody against hepatitis B core antigen for the diagnosis of fulminant type B hepatitis.

We attempted to diagnose fulminant type B hepatitis by the hepatitis B core antibody of the immunoglobulin M class. Of 27 consecutive cases of fulminant hepatitis not due to drug-related causes or type A hepatitis, 11 cases with and 9 without hepatitis B surface antigen in the serum revealed a high activity of immunoglobulin M hepatitis B core antibody by radioimmunoassay (S/N ratio 36.3 +/- 20.3). The remaining 7 cases with presumed non-A, non-B hepatitis, as well as the other 4 cases with drug-related causes, did not show any detectable activity (0.99 +/- 0.16). Serums from 30 asymptomatic carriers did not reveal a high activity of immunoglobulin M hepatitis B core antibody (2.1 +/- 1.2), although titers of non-class-specific hepatitis B core antibody were invariably high. On the basis of the results obtained, immunoglobulin M hepatitis B core antibody may be applied for the diagnosis of type B etiology in cases of fulminant hepatitis with or without hepatitis B surface antigen in the serum.

Adolescent↗
PubMed1982

Maternofetal transmission of IgG-bound hepatitis B e antigen.

Utilizing a highly sensitive radioimmunoassay, hepatitis B e antigen (HBeAg) was detected in the cord serum of eight out of nine babies born to mothers who carried hepatitis B surface antigen together with HBeAg. The titer of HBeAg in the cord serum was much lower than that in the corresponding maternal serum, and escaped the detection by the conventional micro-Ouchterlony immunodiffusion. HBeAg in maternal and cord sera was fractionated into free and IgG-bound moieties by salt precipitation, and their proportion was compared in four pairs. In every pair tested, both free and IgG-bound HBeAg were found in the maternal serum, but only IgG-bound HBeAg was detected in the corresponding cord serum. Based on these results, IgG-bound HBeAg can be transmitted through the placenta, but free HBeAg may barely pass the placenta despite its much smaller size.

Adult↗
PubMed1982

Prognosis of hepatitis B virus surface antigen carriers in relation to routine liver function tests: a prospective study.

The employees of the Japan National Railways Co. working in the Tokyo area, comprising 98% men over the age of 40 yr, were examined for hepatitis B virus seromarkers and routine liver function tests (serum glutamic oxaloacetic transaminase, alkaline phosphatase, and zinc turbidity test) and were followed for 5 yr. The examinees included 202 hepatitis B surface antigen carriers, 502 positive for hepatitis B surface antibody, and 2426 negative for both. We found that the frequency of continuously abnormal liver function test was higher in hepatitis B surface antigen carriers compared with noncarriers. Of the 202 carriers, 4 (1.98%) died from hepatocellular carcinoma with or without cirrhosis, whereas in 2928 noncarriers only 2 (0.07%) died from liver diseases unrelated to hepatitis B virus, the difference being 28.3-fold. Three of the 4 who died from hepatocellular carcinoma initially had normal liver function tests. Mortality in carriers with initially normal liver function tests was 44.5 times higher than that in noncarriers with normal tests. Thus, asymptomatic carriers carry a high risk of dying from chronic liver disease. Routine liver function tests appear of limited value in predicting prognosis.

Adult↗
PubMed1982

Combined passive and active immunization for preventing perinatal transmission of hepatitis B virus carrier state.

Prevention of perinatal transmission of hepatitis B virus carrier state in neonates at high risk was attempted by a combined passive and active immunization. Immediately after delivery, ten babies born to mothers who were asymptomatic carriers of hepatitis B surface antigen (HBsAg) and seropositive for hepatitis B e antigen received an intravenous injection of F(ab')2 fragments (200 IU) derived from hepatitis B immune globulin (HBIG). On the following day, none of them revealed detectable levels of the antibody to HBsAg in their sera, and received an intramuscular injection of HBIG (200 IU) which was repeated at 2 and 4 months of age. Vaccination with 40 micrograms of purified, formalin-inactivated HBsAg particles was given to the nine babies at three months and repeated at 4, 5, and 7 months after birth. All of them maintained detectable levels of the antibody and escaped infection throughout the first 12 months of their lives. The one baby who did not have detectable F(ab')2 in serum for 24 hours developed persistent HBs antigenemia which was noticed as early as seven days after birth.

Adult↗
PubMed1982

High titre of antibody to hepatitis B core antigen detected by immune adherence haemagglutination in HBsAg-positive acute hepatitis.

Nine patients with HBsAg-positive acute hepatitis were tested for antibody to hepatitis B core antigen (anti-HBc) by the immune adherence haemagglutination method. A high anti-HBc titre (2(15) or more) was found in three, while anti-HBc was not detectable in the remaining six. All of them recovered from hepatitis with the return of hepatic function tests to normal, but HBsAg persisted in the three patients whose acute-phase serum had revealed high anti-HBc titres. On the basis of these observations, the three patients were thought to be persistent HBsAg carriers who had contracted opportunistic acute hepatitis of non-B aetiology. Titration of anti-HBc may be indicated in patients with HBsAg-positive acute hepatitis, because it helps distinguish persistent HBsAg carriers with non-B hepatitis from patients with hepatitis B at the outset, during the episode of acute hepatitis.

Antibodies, Viral↗
PubMed1981

Defective immune-adherence (C3b) receptor on erythrocytes from patients with systemic lupus erythematosus.

Erythrocytes from 56 patients with systemic lupus erythematosus (SLE) were tested for the immune-adherence (C3b) receptor reactivity for incubation with aggregated human gamma-globulin (AHG) in the presence of complement. The reactivity of the C3b receptors was expressed as the highest two-fold dilution of AHG that induced haemagglutination. Erythrocytes from 37 (66%) of the SLE patients failed to show any detectable reactivity with AHG, whereas the erythrocytes of only 1 of 51 normal controls matched for age and sex were found to be unreactive. The defect of the C3b receptor reactivity was persistent and could not be restored even after SLE patients had gone into remission with steroid therapy. Moreover, the defect was found frequently in the relatives of patients without detectable immune-adherence reactivity. Owing to its high prevalence and persistence in SLE, the defective erythrocyte C3b receptor may be a useful marker for identifying SLE patients and those predisposed to the disease.

Adolescent↗