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Biomedical subjects

M Mayumi

Publications and source records attributed to M Mayumi.

At least 271 records · Page 15Linked to original sources
PubMed1984

Distribution of IgG subclasses in membranous nephropathy.

The distribution of human IgG subclasses among the glomerular deposits in human membranous nephropathy was examined by immunofluorescence with subclass specific monoclonal antibodies. Large amounts of granular deposits of IgG4 were identified along the capillary loops in all 12 patients, and seven patients had small amounts of IgG1 deposits. Neither IgG2 nor IgG3 deposits were detectable in any of the patients. On the contrary, all four IgG subclasses were detected in membranoproliferative glomerulonephritis and lupus nephritis with a predominance of IgG1 and IgG3. The results indicate that IgG4 is predominant in the glomerular deposits in membranous nephropathy and may play an important role in its pathogenesis.

Complement System Proteins↗
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

A two-site sandwich radioimmunoassay of human fibroblast (beta-) interferon with monoclonal antibodies.

Monoclonal antibodies were produced against human fibroblast (beta-)interferon (IFN-beta). Four of them were directed to the determinant designated a, while the remaining 3 to another determinant named b. An IFN molecule was found to bear one each of a and b determinants arranged in such a manner that the occupation of a with the corresponding antibody did not interfere with the binding of b to its corresponding antibody, and vice versa. This allowed the development of a 2-site sandwich radioimmunoassay in which antibody to b was immobilized on wells of a microtiter plate and the bound antigen was detected by the radiolabeled antibody to a. The 2-site sandwich radioimmunoassay detected, with a high sensitivity, IFN-beta either induced from fibroblast or produced by Escherichia coli harboring the gene of IFN-beta.

Animals↗
PubMed1983

Three-site sandwich radioimmunoassay with monoclonal antibodies for a sensitive determination of human alpha-fetoprotein.

Utilizing monoclonal antibodies against human alpha-fetoprotein, 3 distinct antigenic determinants were identified. These antigenic determinants, provisionally designated a, b and c, were arranged in such a manner that the binding of one determinant with the corresponding antibody did not inhibit, or only barely inhibited the binding of antibodies directed to the other 2 determinants. Monoclonal antibodies with 3 different specificities were, therefore, applied to develop a sandwich-type solid-phase radioimmunoassay of the antigen in which wells were coated with anti-a, and radiolabeled anti-b together with radiolabeled anti-c was employed to detect the bound antigen. The 3-site sandwich radioimmunoassay involving 3 different determinants gave a higher sensitivity than 2-site assays in which only anti-b or anti-c was employed as a radiolabeled reagent, because the radioactivity of the 2 labeled antibodies was added on the antigen bound to immobilized anti-a.

Antibodies, Monoclonal↗
PubMed1983

Immunoglobulin heavy-chain switching in pre-B leukaemias.

Immunoglobulin gene expression is initiated in pre-B cells by rearrangements of heavy-chain variable genes V, D and J, for transcription together with the constant region gene C mu (refs 1-7). The subsequent joining of light-chain V-J genes in the kappa or lambda families leads to formation of complete IgM molecules, which are then expressed on the surface of B cells. Heavy-chain isotype switching has been thought to occur later and to involve CH gene rearrangement via deletion of DNA between a switch site 5' to C mu and a switch site 5' to the downstream C gamma, C epsilon or C alpha gene expressed by a mature plasma cell. On the other hand, isotype switching has been seen in human pre-B-cell leukaemias and in a murine pre-B-cell line before light-chain gene rearrangements and without C mu gene deletion. To explore further the isotype switching in pre-B cells, we used monoclonal antibodies in immunofluorescence assays to allow unambiguous assignment of the heavy-chain isotypes expressed by individual leukaemic cells in 11 pre-B-cell leukaemias. Switching in these leukaemic clones invariably led to expression of gamma 1 heavy-chain and kappa light-chain determinants, occasionally together with gamma 4 and alpha. These results indicate a nonrandom order for heavy-chain isotype switching and for light-chain isotype expression, and also suggest that a mechanism exists for coordinating the two events.

Antibodies, Monoclonal↗
PubMed1983

Studies on corticoid action on the toad tadpole tail in vitro.

The effect of adrenal corticoids on the shrinkage of tail segments from Bufo bufo japonicus tadpoles was studied in vitro. Deoxycorticosterone acetate (DCA) was effective in accelerating the shrinkage of tail segments if thyroxine (T4) or triiodothyronine (T3) was present in the medium. The shrinkage caused by DCA was dose dependent. In the absence of thyroid hormone, DCA did not induce tail resorption. Shrinkage of tail segments induced by DCA and T4 was blocked by prolactin. Among the steroid hormones testes in vitro, aldosterone and corticosterone exhibited a potent activity in accelerating shrinkage of tail segments in the presence of T4. The nature of the corticoid action is discussed.

Adrenal Cortex Hormones↗
PubMed1983

A pitfall in two-site sandwich 'one-step' immunoassay with monoclonal antibodies for the determination of human alpha-fetoprotein.

Utilizing monoclonal antibodies directed to 2 distinct antigenic determinants of the human alpha-fetoprotein (AFP), Uotila, Ruoslahti and Engvall developed the 2-site sandwich immunoassay. They found that due to the different specificities of monoclonal antibodies, 2 antigen-antibody reactions, AFP with immobilized antibody and AFP with labeled antibody, could be accomplished in a single step. We have found, however, that above a certain concentration, AFP detectable by their method decreased because the labeled antibody tended to bind with AFP that failed to react with the immobilized antibody. Consequently, 2 different AFP concentrations produced the same result, and an extremely high, still clinically expectable concentration gave a false negative result. Such an inhibition in high AFP concentrations was not observed in the conventional '2-step' immunoassay within the range of concentrations tested (0.1 ng-3 mg/ml). On the basis of these observations, the 2-site '1-step' immunoassay for AFP would have to be applied on multiple dilutions of the serum to avoid an erroneous interpretation of the results.

Animals↗
PubMed1983

Efficacy of hepatitis B vaccine in chimpanzees given transfusions of highly infective blood.

The protective efficacy of a hepatitis B vaccine against infections from transfusions of large volumes of highly infective blood in five immunized chimpanzees was assessed. Hepatitis B surface antigen (HBsAg) became positive and antibody to HBsAg (anti-HBs) disappeared soon after transfusion in the five chimpanzees. Two chimpanzees that had HBsAg only on the day of transfusion did not develop infection. However, the remaining three chimpanzees with persistent HBsAg antigenemia for three to four days developed serologic evidence of infection. Two chimpanzees did not have hepatitis and the third had a mild, transient case of acute hepatitis. The hepatitis B vaccine prevented the four immunized chimpanzees from developing illness. The remaining chimpanzee developed hepatitis, but a rapid booster response of anti-HBs owing to the previous vaccination appeared to lighten the severity of the disease and prevent chronicity.

Animals↗
PubMed1983

The relationship of hepatitis B surface antigen and antibody to atomic bomb radiation in the Adult Health Study sample, 1975-1977.

A frequency of positive hepatitis B surface antigen (HBsAg) and antibody (anti-HBs) was determined among 2566 atomic bomb survivors in Hiroshima and Nagasaki, Japan during the two-year period 1975 to 1977. The frequency of positive HBsAg (79% of subjects remained persistently antigen positive) was significantly higher in those exposed to 100 rad or more than in the controls. This difference between exposure groups was more marked among the younger age groups. However, contrary to expectation, there was no difference between the dose groups in the distribution by high vs. low titers among the antigen-positive individuals. There was no difference between the two comparison groups in the occurrence of positive anti-HBs reactions (prevalence of hepatitis B virus). The above findings suggest that immune competence, using the prevalence of positive HBsAg as an index, is depressed in the high dose group, but further study, including follow-up of those with persistent positive HBsAg reactions, is called for. With respect to HBsAg subtypes, adr occurs with higher and adw with lower frequency in Nagasaki than in Hiroshima, corresponding to earlier reports for the Japan archipelago of reverse and complementary distributions of these two subtypes.

Adult↗
PubMed1983

Immunochemical structure of hepatitis B e antigen in the serum.

Hepatitis B e antigen (HBeAg) constitutes the nucleocapsid of hepatitis B virus (HBV) and occurs in association with plasma proteins, particularly with IgG, in the serum of persons infected with the virus. A polypeptide with an approximate m.w. of 15,500 (P15.5) is obtained either from HBeAg in the serum or from the nucleocapsid of HBV. P15.5 preparations from serum and virus resembled closely each other in the amino acid composition. The C-terminus amino acid sequence of P15.5 from serum was determined to be -Thr-Thr-Val-Val, whereas that from the virus ended with -Thr-Thr. The same sequence of four amino acid residues was found on the gene coding for the nucleopeptide of hepatitis B virus with a molecular size of 19,000 daltons (P19). P15.5 identified on the nucleotide sequence of P19 was composed of 149 amino acid residues with a calculated molecular size of 16,770 daltons. The gene coding for P19 had two -Asp-Pro-connections. By splitting these connections in P19 and P15.5 preparations with formic acid, smaller polypeptides were obtained with sizes predicted from the nucleotide sequence and with the N-terminus amino acid of proline as expected. One of two monoclonal antibodies raised against the core of Dane particles (HBcAg) bound with P15.5 preparations purified from serum and HBV. The IgG fraction from a human serum containing antibodies to HBcAg but not to HBeAg bound with P15.5 also. On the basis of the results obtained, the IgG molecules associated with P15.5 in the serum of persons infected with HBV may well represent the antibodies against HBcAg with limited specificities.

Amino Acid Sequence↗
PubMed1983

IgG subclass expression by human B lymphocytes and plasma cells: B lymphocytes precommitted to IgG subclass can be preferentially induced by polyclonal mitogens with T cell help.

The human IgG subclasses expressed by circulating B lymphocytes, tissue plasma cells, and plasma cells generated from B cell precursors in response to the polyclonal mitogens LPS and PWM were examined by immunofluorescence using subclass-specific monoclonal antibodies. The subclass distribution observed for circulating B lymphocytes was IgG2 (48%) greater than IgG1 (40%) greater than IgG3 (8%) greater than IgG4 (1%), while the distribution among IgG plasma cells in bone marrow, blood, spleen, and tonsils was IgG1 (64%) greater than IgG2 (26%) greater than IgG3 (8%) greater than IgG4 (1%). Multiple IgG isotypes were not observed on B cells or in plasma cells. Although IgG plasma cell responses to both LPS and PWM were T cell dependent, the distributions of IgG subclasses elicited were strikingly different. In control and LPS-stimulated cultures of blood mononuclear cells, the induced plasma cells expressed the IgG subclass distribution: IgG2 greater than 80%, IgG1 less than 20%, IgG3 less than 1%, IgG4 less than 1%. In PWM-stimulated cultures, the subclass distribution, IgG1 approximately 65%, IgG2 approximately 25%, IgG3 approximately 7%, IgG4 approximately 1%, was in perfect concordance with the in vivo subclass distribution of IgG plasma cells. Selective inhibition of suppressor T cell activity by x-irradiation and mitomycin C treatment did not alter the IgG subclass distribution pattern induced by LPS and PWM. Monoclonal antibodies were used to deplete selectively the B cell precursors bearing IgG1, IgG2, or IgG3 before PWM stimulation of blood mononuclear cells. In each instance, a reduction was observed only in the subpopulation of plasma cells producing the homologous IgG subclass. The results indicate that T cells can preferentially influence the terminal differentiation of B cells that are precommitted to different IgG subclasses.

Animals↗
PubMed1983

A hepatitis B surface antigen polypeptide (P31) with the receptor for polymerized human as well as chimpanzee albumins.

Hepatitis B virus, and hepatitis B surface antigen particles co-occurring with hepatitis B e antigen, have the receptor for polymerized human and chimpanzee albumins that may be involved in the hepatotropism of hepatitis B virus. We identified the receptor on a hepatitis B surface antigen polypeptide with a molecular size of 31,000 daltons (P31). P31 bound to polymerized albumins from human and chimpanzee, but did not react with polymerized albumins from the experimental animals without susceptibility to hepatitis B virus. P31 was composed of the major polypeptide of hepatitis B surface antigen with a molecular size of approximately 22,000 daltons (P22) and additional 55 amino acid residues coded by the pre-S region in the hepatitis B virus-specific deoxyribonucleic acid. Because P22 did not react with polymerized albumin, the sequence of 55 amino acid residues in the pre-S region appeared to bear the receptor. Polypeptides with the receptor for polymerized albumin may make an efficacious hepatitis B vaccine, because they could raise antibodies against the putative site on hepatitis B virus capable of binding with hepatocytes to initiate the infection.

Amino Acids↗
PubMed1983

Distinction of two subtypes of human leukocyte interferon (IFN-alpha) on B cell activation. B cell proliferation by two subtypes of IFN-alpha.

We examined the effect of interferon (IFN), with particular emphasis on the effects of the two subtypes of IFN-alpha (IFN-alpha A and IFN-alpha B) on the B cell proliferation induced by Staphylococcus aureus Cowan I bacterium (SpA Col). An increase of SpA Col-induced proliferation was observed in the presence of 100 to 1000 U/ml of IFN-alpha, but a decrease of SpA Col-induced proliferation was observed in the presence of 1000 to 10,000 U/ml of IFN-beta. The two subtypes of IFN-alpha had different effects on cell proliferation; a significant enhancement was shown in the presence of 1000 to 10,000 U/ml of IFN-alpha A, but inhibition was shown in the presence of 1000 to 10,000 U/ml of IFN-alpha B. In the reconstitution test of the two subtypes of IFN-alpha, the boundary between enhancement and inhibition of SpA Col-induced proliferation was revealed when the proportion of IFN-alpha A and IFN-alpha B (IFN-alpha A:IFN-alpha B) ranged between 8:2 and 9:1. Toward the SpA Col-induced responses, the above IFN were all found to act on B cells directly, independent of the presence of T cells. Proliferative responses by IFN-alpha and IFN-alpha A, however, were shown to be slightly dependent on the presence of monocytes. The lymphocyte proliferation induced by other mitogens (phytohemagglutinin, concanavalin A, pokeweed mitogen, and protein A of S. aureus) were all inhibited by the above IFN.

B-Lymphocytes↗
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

Immunoglobulin VH determinants defined by monoclonal antibodies.

Hybridoma clones secreting antibodies against common VH determinants were readily produced by fusion of cells from mice immunized with isolated V mu fragments of human immunoglobulins (Ig), but not with intact Ig molecules or isolated heavy chains. Four monoclonal antibodies to the V mu fragments of different IgM paraproteins were selected for analysis: MH-44 (mu kappa), GB-24 (mu kappa), NF-11 (gamma 1 kappa), and SA-44 (gamma 1 kappa). Each antibody reacted with the homologous V mu fragment, homologous mu chain, and normal gamma chains, but not with the intact IgM molecules, intact IgG, or isolated light chains, as determined by radioimmunoassay. The VH reaction spectra with a panel of myeloma heavy chains showed overlapping but distinctive patterns for the four antibodies. Each of the four monoclonal anti-VH antibodies appeared to react with a different "hidden" VH determinant that is not exposed on undenatured, intact Ig molecules and differs from conventional VH subgroup determinants. In immunofluorescence studies, the monoclonal anti-VH antibodies did not bind to surface Ig on viable B lymphocytes, but visibly stained subpopulations of fixed B lymphocytes, pre-B cells, and normal plasma cells. The mean frequencies of VH+ plasma cells were 30% (MH-44), 17% (GB-24), 13% (NF-11), and 3% (SA-44), and similar frequencies were obtained for the VH+ B cell subpopulations. While subpopulations of B cells could be identified at all stages in differentiation by immunofluorescence with the anti-VH antibodies, neither resting nor activated T cells expressed these VH determinants in detectable amounts.

Animals↗
PubMed1982

Determination of the antibody to hepatitis B e antigen by the inhibition on electrophoresis of free e antigen.

A new method is described for the rapid and sensitive detection of the antibody to hepatitis B e antigen (anti-HBe) in serum. Twenty-five microliters of the test serum were incubated with 10 microliter of the purified small 'free' e antigen, and then the consumption of the added antigen was detected by the failure to precipitate with standard anti-HBe in counter-electrophoresis. When a total of 444 serums from asymptomatic carriers of hepatitis B surface antigen was tested for anti-HBe by this method, 348 (78.4%) were found to be positive with a detectability much higher than that of the passive hemagglutination method which detected the antibody in only 264 (59.5%) of the same serums.

Antibodies, Viral↗
PubMed1982

Demonstration of two distinct antigenic determinants on human alpha-foetoprotein by monoclonal antibodies.

Mice were immunized with a purified preparation of human alpha-foetoprotein (AFP) and their spleen cells were hybridized with mouse myeloma cells. Eleven hybridoma cell lines secreting antibody to AFP were obtained. These antibodies were classified into two groups on the basis of different antigenic determinants they recognized. Seven cell lines produced antibodies directed to one determinant of AFP (determinant a), while the remaining 4 produced antibodies to another determinant (determinant b). A native AFP molecule bore one each of a and b determinants which were accessible by monoclonal antibodies; it was detected by a sandwich-type solid-phase radioimmunoassay only when antibody to a was used for coating wells of the microtitre plate and antibody to b as radiolabelled reagent, or vice versa. The presence of two different antigenic determinants on AFP was further confirmed by a chemical modification. When AFP was reduced in the presence of 2 mM dithiothreitol and then alkylated, determinant b was completely destroyed, but the determinant a remained unaffected. Furthermore, reduced and alkylated AFP was detected by the radioimmunoassay employing antibody to a both for coating wells and as radiolabelled reagent, thereby indicating that it bore two determinant as, one of which had been unaccessible in the native AFP.

Alkylation↗