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Biomedical subjects

M Mayumi

Publications and source records attributed to M Mayumi.

At least 289 records · Page 16Linked to original sources

A glycopeptide containing 15 amino acid residues derived from hepatitis B surface antigen particles: demonstration of immunogenicity to raise anti-HBs in mice.

The major polypeptides composing hepatitis B surface antigen (HBsAg) particles are P-I and P-II. P-II shares the same amino acid sequence as P-I and contains an additional carbohydrate moiety of mol. wt approximately 5000. When a purified preparation of P-II was digested with Nagarse and then with Pronase P, it gave rise to a glycopeptide containing 15 amino acid residues and the carbohydrate moiety of P-II. The N-terminal amino acid sequence of the glycopeptide was determined to be Lys-Pro-Thr-Asp-Gly-Asn-. The polysaccharide moiety contained 5 moles of N-acetylglucosamine and was connected with Asn at the sixth position from the N-terminus. When mice were immunized against this HBsAg glycopeptide, they raised humoral antibodies which bound to each of three preparations of P-I derived from HGsAg particles of subtypes adw, adr and ayw, thereby indicating that the sequence of 15 amino acids in the glycopeptide would constitute a common antigenic structure of HBsAg.

Amino Acid Sequence↗

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↗

Retardation of thyroxine-induced metamorphosis by Amphenone B in toad tadpoles.

The effect of Amphenone B, an inhibitor of corticoid synthesis, on thyroxine (T4)-induced metamorphosis was studied in toad tadpoles kept in thiourea. Amphenone injections retarded T4-induced tail resorption markedly. The effect of Amphenone was nullified by aldosterone and corticosterone added to the water in which tadpoles were kept. Steroidogenic cells of adrenals in Amphenone-injected animals were enlarged markedly as compared with those in the saline-injected tadpoles or the Amphenone-injected tadpoles which were supplemented with corticoids. The results strongly suggest that endogenous corticoids act together with thyroid hormone to accelerate metamorphosis.

Adrenal Cortex Hormones↗

Demonstration of two distinct antigenic determinants on hepatitis B e antigen by monoclonal antibodies.

Mice were immunized against hepatitis B e antigen (HBeAg) isolated from sera of asymptomatic carriers of hepatitis B virus. Their spleen cells were fused with mouse myeloma (NS-1) cells, and 5 clones of hybridoma cells secreting antibody against HBeAg (anti-HBe) were isolated. For the production of anti-HBe in large scale, cells were cultivated both in vitro and in the peritoneal cavity of ascitic mice. Although monoclonal antibodies produced by these clones showed a strong reactivity of anti-HBe in hemagglutination tests, individual monoclonal anti-HBe did not reveal any precipitin line in immunodiffusion. When 2 of the 5 monoclonal antibodies were mixed together, however, some combinations showed a precipitin line against HBeAg, whereas others did not. Utilizing solid-phase radioimmunoassay involving a number of combinations of monoclonal antibodies used for solid-phase and radiolabeling, the 5 antibodies were classified into 2 groups. Three of the anti-HBe antibodies were found to be directed to 1 determinant of HBeAg (determinant a); the remaining 2 to the other determinant (determinant b). Determinants a and b were detected on HBeAg in the serum, as well as on the polypeptide of 19,000 daltons (P19) derived from the nucleocapsid of hepatitis B virus. Monoclonal anti-HBe antibodies with different specificities may provide useful tools in delineating the antigenic structure of HBeAg and also in evaluating immune responses of the host directed to its subdeterminants.

Animals↗

Potentiation of natural killer cell activity of human lymphocytes in vitro: the participation of interferon in stimulation with Staphylococcus aureus Cowan I bacteria but not with protein A.

In the previous paper we reported that human natural killer (NK) cell activity was augmented greatly by preincubation with Staphylococcus aureus Cowan I bacteria (SpA CoI) or its Protein A. We examined here whether the augmentation with these stimulants is ascribable to the direct activation of NK cells or mediated by some soluble factors produced by the stimulants. It was found that a significant amount of interferon (IFN) was produced by the SpA CoI-stimulation but not by the Protein A-stimulation, although the latter usually induced augmentation of NK-cell activity not less than SpA CoI-stimulation. IFN produced by SpA CoI was considered to belong to alpha-type IFN, because it was stable at pH 2.0 and could be neutralized effectively by anti-IFN alpha antibody. Kinetics of NK-cell activation by SpA CoI (but not by Protein A) were very similar to those by IFN alpha. Furthermore, augmentation of NK-cell activity with SpA CoI-stimulated supernatant was inhibited almost completely by diluted anti-IFN alpha antibody, whereas augmentation with Protein A-stimulated supernatant could not be abolished by the same treatment. It was, therefore, suggested that augmentation of NK-cell activity with SpA CoI might be ascribable in most part to the IFN induced, whereas Protein A can stimulated NK or T cells directly or soluble factors other than IFN might work as well.

Antibodies, Viral↗

Non-A, non-B (type 1) hepatitis agent capable of inducing tubular ultrastructures in the hepatocyte cytoplasm of chimpanzees: inactivation by formalin and heat.

We have reported two kinds of viruslike particles derived from human sera that induced morphologically and serologically different types of non-A, non-B hepatitis in chimpanzees. A chimp serum containing one such agent capable of inducing a type of hepatitis with cytoplasmic tubular ultrastructures (non-A, non-B, type 1) was titrated for its infectivity in chimps. Two chimps who received 1 ml of a 10(-2) dilution of the original serum developed the characteristic morphological changes in the liver together with elevated serum transaminase levels, while the other two who received 1 ml of a 10(-4) dilution failed to show such changes. The two who escaped the infection were proven to be susceptible to the agent, because they developed non-A, non-B, type 1 hepatitis when they were challenged by 1 ml of a 10(-1) dilution of the same serum on the 23rd week after the first inoculation. One milliliter of a 10(-1) dilution containing more than 10 chimp infecting units were inactivated in the presence of 1/2000 formalin or by heating at 100 degrees C for 5 min and then given to four other chimps. None of them developed clinical or histologic evidence of non-A, non-B, type 1 hepatitis, thereby indicating that both formalin and heat could destroy the ability of the agent to induce this type of hepatitis.

Animals↗

Studies on the clonal origin of human B cell leukemia using monoclonal anti-idiotype antibodies.

The clonal origin of an IgA1 kappa B cell leukemia in a 71-year-old man (WF) was examined using a monoclonal anti-Id antibody and a panel of monoclonal anti-VH antibodies. Immunofluorescent studies revealed that all surface IgA1 kappa + leukemic cells in WF's blood and 10% of the IgM+ B cells in his bone marrow expressed the WF Id. Three percent of the IgA1 kappa + leukemic cells in blood also expressed gamma-chains in their cytoplasm. Approximately 0.1%, 1%, and 10% of bone marrow mononuclear cells, respectively, expressed mu-chains, gamma-chains, and alpha-chains in their cytoplasm, but no detectable light chains or surface immunoglobulins. These mu, gamma, and alpha-positive cells had the convoluted nucleus and narrow cytoplasm characteristic of normal mu+ pre-B cells. Sequential isotype switching among this unusual pre-B population was indicated by co-expression of mu-chains and alpha-chains by 11% and 63%, respectively, of the gamma pre-B cells. These pre-B cells and the surface alpha-chains and cytoplasmic gamma-chains of the leukemic B cells were reactive with one of four monoclonal anti-VH antibodies. The data suggest malignant transformation of the clone before isotype switching, and also imply light chain precommitment at the pre-B cell level of differentiation.

Aged↗

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↗

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↗

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↗

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↗

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↗

Demonstration of the immunogenicity of hepatitis B core antigen in a hepatitis B e antigen polypeptide (P19).

The core of Dane particles, the presently accepted hepatitis B virus nucleocapsid, contains two polypeptides (P19 and P45) with the antigenicity of hepatitis B e antigen (HBeAg). The antigenicity of hepatitis B core antigen (HBcAg) was not detectable in either of them by the conventional in vitro assay methods, despite the fact that both of these polypeptides were derived from the core of Dane particles. When a rabbit had been immunized with the purified preparation of P19 emulsified in complete Freund's adjuvant, however, humoral antibody against HBcAg was produced in addition to the antibody against HBeAg. Amino acid analysis of P19 disclosed a high content of arginine (12.9%), leucine (11.9%), serine (10.3%) and proline (10.2%). The amino acid composition of P19 was found to be strikingly similar to the composition of the 183 amino acid sequence deduced from the sequence of hepatitis B virus DNA which has been presumed to be encoding HBcAg. We conclude that both HBeAg and HBcAg are antigenic determinants borne by the major polypeptide (P19) constituting the core of Dane particles.

Amino Acids↗

Glomerulonephritis associated with arteritis in marmosets infected with hepatitis A virus.

Seven of 8 marmosets (Saguinus oedipus and Saguinus labiatus) injected i.v. with different inocula of hepatitis A virus isolated from patients in the acute phase of disease developed proliferative glomerulonephritis associated with arteritis. The glomerulonephritis was characterized by immunofluorescent and electron-dense deposits and hypercellularity. Although no antigenic component of the glomerular immune complex was detected, this glomerulonephritis and arteritis may be diagnosed morphologically as an immune complex disease. These findings show the possibility of the appearance of exohepatic disease as an immunologically mediated disease in human hepatitis A virus infection.

Animals↗

Demonstration of two different types of non-A, non-B hepatitis by reinjection and cross-challenge studies in chimpanzees.

Utilizing immune electron microscopy, viruslike particles were identified in the serums of three apparently healthy, HBsAg-negative blood donors. The serum from one of the donors, when injected into two susceptible chimpanzees, induced non-A, non-B hepatitis with an increase in SGPT level and pathological changes in the liver compatible with acute hepatitis but none of the cytoplasmic ultrastructures previously noted by electron microscopy in non-A, non-B hepatitis. These two chimps did not contract hepatitis when the same inoculum was given again 17 wk after the first injection. When they were subsequently challenged, however, by a chimp inoculum containing viruslike particles known to induce non-A, non-B hepatitis with cytoplasmic tubular ultrastructures, they developed high SGPT levels and these characteristic ultrastructures in their hepatocytes. A third chimp was initially injected with the chimp inoculum containing viruslike particles known to induce hepatitis with tubular ultrastructures, reinjected with the same agent, and then challenged by the human serum containing viruslike particles capable of inducing non-A, non-B hepatitis without tubular ultrastructures. He developed biochemical and pathological evidence of acute hepatitis after the first and the third, but not after the second inoculations. There are at least two kinds of viruslike particles which are associated with infectivity for two different types of non-A, non-B hepatitis; these have been tentatively designated NANB-1 and NANB-2.

Alanine Transaminase↗

A case of membranous glomerulonephritis in which positive to negative change of hepatitis B e antigen in glomeruli was observed.

9-year-old boy suffering from membranous glomerulonephritis (GN) associated with hepatitis B virus (HBV) infection was observed. In this case seroconversion from hepatitis B e antigen (HBeAg) to hepatitis B e antibody (HBeAb) could not be confirmed, but a change from HBeAg positive to negative in the glomeruli was observed, and electron-dense deposits (EDD) became translucent and urinary protein also turned negative. These findings apparently suggest the possibility that membranous GN in this case is closely concerned with the causation and development of HBeAg.

Child↗

Hepatitis B e antigen-mediated membranous glomerulonephritis. Correlation of ultrastructural changes with HBeAg in the serum and glomeruli.

Immunopathologic findings in the glomeruli of six children with membranous glomerulonephritis who were carriers of hepatitis B virus were compared with serum markers of hepatitis B virus infection. Four of the patients were positive for hepatitis B e antigen (HBeAg) in the serum, were grossly proteinuric, and had abnormal liver function tests. Deposition of HBeAg, together with immunoglobulins and beta 1C, was found in the glomeruli of these patients. On electron microscopy, numerous electron-dense deposits were identified on and within the glomerular basement membrane. The remaining two patients were seropositive for antibody against HBeAg (anti-HBe); although they had previously suffered from active membranous glomerulonephritis with massive proteinuria, they were no longer proteinuric at the time of the last renal biopsy. Deposition of HBeAg was not detected in their glomeruli. Electron microscopic observation disclosed numerous electron-lucent areas which had replaced electron-dense deposits, indicating regression of the disease processes. These results delineate the etiologic role of HBeAg in maintaining active membranous changes and suggest that patients with HBeAg-mediated membranous glomerulonephritis may remit as they seroconvert from HBeAg to anti-HBe.

Adolescent↗