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Biomedical subjects

M Mayumi

Publications and source records attributed to M Mayumi.

At least 199 records · Page 11Linked to original sources
PubMed1990

Agranulocytosis following infectious mononucleosis.

A girl developed acute agranulocytosis (45/mm3), 37 days after the onset of infectious mononucleosis. The bone marrow showed myeloid hyperplasia with maturation arrest and erythroid hypoplasia. A normal amount of colony forming units of granulocytes and macrophages (CFU-GM) colonies with a relative high number of clusters was observed. Neither anti-neutrophil antibodies nor circulating inhibitors of colony growth were found in serum. Granulocyte and macrophage colony stimulating factor (GM-CSF) activity in the patient's serum rose at this time. The agranulocytosis lasted 5 days and her clinical state soon improved. These results suggested that agranulocytosis was presumably not due to serum factors, including auto-antibodies and/or suppressive substances, and that Epstein-Barr virus (EBV) had some direct or indirect effect on the marrow cells of the myeloid series.

Agranulocytosis↗
PubMed1990

Chronic active hepatitis with hepatitis B virus DNA and antibody against e antigen in the serum. Disturbed synthesis and secretion of e antigen from hepatocytes due to a point mutation in the precore region.

Some patients with type B chronic active hepatitis have a high titer of hepatitis B virus DNA despite antibody against e antigen in the serum. Clones of hepatitis B virus were propagated from the sera of seven patients with this disease, and the precore region was sequenced. Essentially all clones (128/131 or 98%) showed a point mutation from guanine to adenine at nucleotide 83, converting codon 28 for tryptophan (TGG) to a stop codon (TAG); the second guanine-to-adenine point mutation at nucleotide 86 was identified in only 29 clones from two patients. In patients followed up since they had hepatitis B e antigen, a shift from guanine to adenine was observed at nucleotide 83 along with the seroconversion to the antibody to e antigen. The precore-region product is required for the synthesis and secretion of e antigen from hepatocytes. A point mutation from guanine to adenine at nucleotide 83 observed in the seven patients, therefore, would be responsible for disturbed secretion of e antigen.

Aged↗
PubMed1990

Hepatitis B surface antigen particles with all four subtypic determinants: point mutations of hepatitis B virus DNA inducing phenotypic changes or double infection with viruses of different subtypes.

Hepatitis B surface antigen (HBsAg) particles carry the common determinant, a, as well as d or y and w or r subtype determinants, and are classified into the four major subtypes, i.e., adw, adr, ayw and ayr. Rare sera contain HBsAg particles with all four subtype determinants (adywr). Target sequences (nucleotides 38-550) in the S gene of hepatitis B virus (HBV) DNA in two such sera were amplified by the polymerase chain reaction. Individual amplification products were cloned in an M13 phage vector. The HBV DNA clones obtained were subtyped by determining the second letters of codon 122 and 160 for lysine (AAA/AAG) or arginine (AGA/AGG), which specify the d or y and w or r determinants, respectively. From one serum (S-63), two adw, 10 adr and 58 ayr clones were obtained. When the two adw clones and two representatives each of the adr and ayr clones were compared against each other, for the sequence of 235 base pairs representing nucleotides 295-529 in the S gene, they differed only by 0.4-2.1% (average 1.2%). These results indicated multiple point mutations of a single HBV strain of subtype ayr and co-infection of hepatocytes with the original HBV strain and its mutant of subtype adw as the mechanism for the production of HBsAg/adywr particles. From the other serum (K-45), 1 adw, 73 adr and 4 ayw clones were obtained. The adw clone and two representative adr clones differed only by 0-1.7% in the S gene sequences, but they differed by 8.5% or greater from two representative ayw clones. HBsAg/adywr particles in this serum, therefore, could be explained by double infection of hepatocytes with two HBV strains of different subtypes (adr and ayw).

Arginine↗
PubMed1990

Transforming growth factor beta and dexamethasone suppress the expression of Fc epsilon receptor 2 (CD23) on a human eosinophilic cell line EoL-3.

The effects of interferon-alpha (IFN-alpha), INF-gamma, transforming growth factor beta (TGF-beta) and dexamethasone on low-affinity Fc receptors for IgE (Fc epsilon R2/CD23) expression on a human eosinophilic leukemia cell line, Eol-3, were examined. Fc epsilon R2/CD23 expression was enhanced by both IFN-alpha and IFN-gamma, and suppressed by TGF-beta and dexamethasone. Northern blot analysis revealed that these reagents regulate the Fc epsilon R2/CD23 expression from mRNA level: both IFN-alpha and IFN-gamma increased the amount of Fc epsilon R2/CD23 mRNA, while both dexamethasone and TGF-beta decreased Fc epsilon R2/CD23 mRNA, where the effect of dexamethasone was much stronger than that of TGF-beta. In comparison with IFN-alpha, IFN-gamma seemed to enhance preferentially the release of surface Fc epsilon R2/CD23, which resulted in the increase of soluble Fc epsilon R2/CD23. These results suggest that these reagents may play important regulatory roles in allergy and in helminth infections via their effects on Fc epsilon R2/CD23 expression on eosinophils.

Antigens, CD↗
PubMed1990

Subtyping hepatitis B virus DNA in free or integrated forms by amplification of the S-gene sequences by the polymerase chain reaction and single-track sequencing for adenine.

The S-gene fragments of hepatitis B virus (HBV) DNA in serum, or integrated in chromosomes of human hepatoma cells (PLC/PRF/5), were amplified by the polymerase chain reaction, cloned into an M13 phage vector, and then sequenced only for adenine. The subtype determinant d or y was established by the presence or absence of adenine as nucleotide 365, and w or r by that of nucleotide 479 in the S gene. The results were identical with those obtained by enzyme immunoassay with monoclonal antibodies. A high sensitivity for the detection of HBV DNA, amplified by the polymerase chain reaction, allowed subtyping of HBV in sera containing HBsAg in concentrations too low to be subtyped by immunological methods. Furthermore, subtyping at the nucleotide level can be applied to tissues containing HBV DNA sequences in integrated forms, such as hepatocellular carcinomas, stored frozen or in formalin.

Adenine↗
PubMed1990

Trans-complementation of the C gene of human and the P gene of woodchuck hepadnaviruses.

A 5 bp insertion was introduced into the BstEII site at nucleotide 2815 in DNA of hepatitis B virus (HBV) and a mutant HBV genome was produced, which coded for envelope and core proteins, but not for DNA polymerase, due to a frameshift. Cultured hepatoma cells (HepG2) were simultaneously transfected with a plasmid harbouring a tandem dimer of the mutant HBV DNA and another plasmid harbouring a tandem dimer of DNA of woodchuck hepatitis virus or duck hepatitis B virus. The replication of mutant HBV DNA, incapable of encoding DNA polymerase, was accomplished by cotransfecting woodchuck hepatitis virus DNA, but not by duck hepatitis B virus DNA. These results indicated a trans-complementation of the C and P genes in mammalian hepadnaviruses beyond a species barrier.

Animals↗
PubMed1990

Hepatitis B viruses with precore region defects prevail in persistently infected hosts along with seroconversion to the antibody against e antigen.

The C gene of hepatitis B virus (HBV) codes for a nucleocapsid protein made of 183 amino acid residues and is preceded in phase by the precore (pre-C) region, encoding 29 residues. The pre-C-region product is required for the synthesis and secretion of hepatitis B e antigen (HBeAg), which is made of the C-terminal 10 amino acid residues of the pre-C-region product and the N-terminal 149 residues of the C-gene product. HBV mutants with pre-C-region defects prevailed in the circulation of three asymptomatic carriers as they seroconverted from HBeAg to the corresponding antibody (anti-HBe), and these mutants finally replaced nondefective HBV. HBV DNA clones were propagated from sera of an additional 15 carriers with anti-HBe and sequenced for the pre-C region. Essentially all HBV DNA clones (56 of 57 [98%]) revealed mutations that prohibited the translation of a functional pre-C-region product. A point mutation from G to A at nucleotide 83, converting Trp-28 (TGG) to a stop codon (TAG), was by far the commonest and was observed in HBV DNA clones from 16 (89%) of 18 carriers seropositive for anti-HBe. In addition, there were point mutations involving ATG codon to abort the translation initiation of the pre-C region, as well as deletion and insertion to induce frameshifts. Such mutations leading to pre-C-region defects were rarely observed in persistently infected individuals positive for HBeAg or in patients with type B acute hepatitis after they had seroconverted to anti-HBe. These results would indicate a selection of pre-C-defective mutants in persistently infected hosts, along with seroconversion to anti-HBe, by immune elimination of hepatocytes harboring nondefective HBV with the expression of HBeAg.

Amino Acid Sequence↗
PubMed1990

Gamma-interferon production in response to hepatitis B core protein and its synthetic peptides in patients with chronic hepatitis B virus infection.

The nucleocapsid of hepatitis B virus (HBV) is an efficient immunogen in activating T cells to produce interferon-gamma (IFN-gamma) in patients with chronic HBV infection. We investigated hepatitis B core antigen (HBcAg)-specific T cell recognition, which seems to be implicated in the pathogenesis of chronic liver disease. IFN-gamma production by peripheral-blood mononuclear cells of patients with chronic HBV infection [25 patients with chronic active hepatitis (CAH) and 14 asymptomatic carriers of HBV (ASCs)] was measured by an enzyme-linked immunosorbent assay. P19 polypeptide, which is derived from recombinant HBcAg particle (rHBcAg), increased IFN-gamma production in patients with CAH, but its effect was weaker than that of rHBcAg. P19 had no stimulating effect on T cells from ASCs. The fine specificity of T cell recognition of HBcAg was examined using 8 kinds of synthetic peptides. T cells from the patients who responded against P19 polypeptide recognized the sites within the common sequences of HBcAg and HBeAg (p72-90, P90-99, P108-122 and P126-146). These results suggest that HBcAg and P19 are cross-reactive at the T cell level, and that these T cells recognize the sites within the common sequences of HBcAg and HBeAg in HBV-infected patients.

Adult↗
PubMed1990

Common and subtypic determinants of hepatitis B surface antigen particles: susceptibility to reduction and/or alkylation evaluated with monoclonal antibodies.

The specificity of five monoclonal antibodies, three raised against hepatitis B surface antigen (HBsAg) particles and two against envelope polypeptides, was tested for on a panel of 366 sera containing HBsAg of various subtypes (131 adw, 146 adr, 39 ayw and 50 ayr). Three monoclonals bound to HBsAg irrespective of subtypes, and therefore, were directed to the common antigenic determinants of HBsAg. Of these, two raised against particles (No. 824 and No. 7922) did not bind with reduced HBsAg particles. The other raised against peptides (No. 5124) bound to reduced HBsAg particles. It did not, however, bind to reduced and alkylated HBsAg particles, thereby indicating that it was directed to an epitope involving cysteine residues not contributing to the conformation. The remaining two monoclonals were directed to subtypic determinants not identical to any of d, y, w and r determinants. The subtypic determinant detectable by one of them (No. 4403), raised against HBsAg polypeptides, markedly increased after reduction of HBsAg particles with or without alkylation. In contrast, the subtypic determinant, detectable by the other monoclonal (No. 2155) raised against particles, substantially decreased after reduction. Non-identity of common or subtypic determinants detectable by the five monoclonals were established by blocking tests in which labeled antibody was competed by non-labeled antibody, of a homologous or heterologous specificity, for the binding with HBsAg. These monoclonals would be useful in studies for immunochemical configuration of HBsAg particles and epidemiology of novel subtypic determinants.

Alkylation↗
PubMed1990

Ketotifen inhibits PAF-induced actin polymerization in a human eosinophilic leukaemia cell line, EoL-1.

The inhibitory effect of ketotifen on platelet activating factor (PAF)-induced actin polymerization in a human eosinophilic leukaemia cell line, EoL-1, was examined by flow cytometry with the use of reagents specific for the filamentous form of actin (F-actin). Actin polymerization has been considered to be essential for locomotion of cells, chemotaxis and chemokinesis, and thus it reflects the chemotactic reaction of EoL-1 cells stimulated by PAF. Unstimulated EoL-1 cells showed little PAF-induced actin polymerization, whereas EoL-1 cells cultured for 9 days with the supernatant of a human ATL cell line, HIL-3 (HIL-3 sup), showed marked actin polymerization when stimulated with PAF. The actin polymerization in EoL-1 cells induced by PAF was seen in a dose-dependent manner at concentrations of 10(-10) M to 10(-6) M of PAF, and the maximum effect was seen at 10(-7) M of PAF. CV-3988, a specific antagonist of PAF, inhibited 80% of the actin polymerization in EoL-1 cells induced by PAF at a concentration of 10(-5) M. Ketotifen inhibited up to 40% of the PAF-induced actin polymerization of EoL-1 cells in a dose-dependent manner at concentrations of 10(-9) M to 10(-5) M. These results suggest that ketotifen may play an important role in the prevention of eosinophil-induced inflammation in allergic disorders by inhibiting PAF-induced chemotaxis of eosinophils.

Actins↗
PubMed1990

The 5'-terminal sequence of the hepatitis C virus genome.

The 5'-terminal sequence of the genome of hepatitis C virus (HCV) was determined for two distinct HCV strains in human and chimpanzee carriers. It had a 5'-noncoding region of at least 324 nucleotides, well preserved by the two strains with a high homology (99.1%), followed by 1348 nucleotides that continued to the documented sequence of prototype HCV spanning 7310 nucleotides (European Patent Application #88310922.5). Based on these results, HCV is considered to possess an uninterrupted open reading frame encoding at least 2886 amino acid residues. Two structural genes were postulated on the 5'-terminal sequence of the HCV genome. One gene in the upstream region, highly conserved by the two strains at the amino acid level and rich in basic amino acids such as arginine, appeared to encode the viral capsid protein. The other gene in the downstream region was divergent between the two strains at both nucleotide and amino acid levels. It coded for nine potential N-glycosylation sites, and was considered to encode the viral envelope protein. Disclosure of the 5'-terminal sequence of the HCV genome would facilitate its taxonomic classification, and contribute toward immunological diagnosis of infection and development of vaccines.

Amino Acid Sequence↗
PubMed1989

Regulation of Fc gamma receptor expression and phagocytosis of a human monoblast cell line U937. Participation of cAMP and protein kinase C in the effects of IFN-gamma and phorbol ester.

We investigated the positive and negative effects of IFN-gamma, PMA, dibutyryl cAMP (Bt2cAMP), dexamethasone and transforming growth factor-beta (TGF-beta) on Fc gamma R subtype expression and phagocytosis of a human monoblast cell line, U937. IFN-gamma increased and Bt2cAMP decreased Fc gamma RI expression determined by a mAb 32.2, whereas PMA and Bt2cAMP increased Fc gamma RII expression determined by a mAb IV-3. Phagocytosis was measured microscopically by counting ingested aggregated human IgG- or BSA-treated ox E (Eo'-IgG or Eo'-BSA). IFN-gamma increased the phagocytosis of Eo'-IgG but not that of Eo'-BSA, and PMA increased the phagocytosis of both Eo'-IgG and Eo'-BSA. Bt2cAMP decreased both basal and IFN-gamma- and PMA-augmented phagocytosis of U937 cells. Dexamethasone also inhibited both basal and IFN-gamma-augmented Fc gamma RI expression and PMA-augmented Fc gamma RII expression and phagocytosis, but did not affect IFN-gamma-augmented phagocytosis of Eo'-IgG. The augmentation of phagocytosis of Eo'-IgG by IFN-gamma thus seems to be due mainly to the increased internalizing process rather than to increased Fc gamma RI expression. TGF-beta slightly decreased Fc gamma R expression. In a study of the participation of protein kinase C (PK-C), it was found that H-7, a PK-C inhibitor, did not inhibit either IFN-gamma- or PMA-enhanced Fc gamma RI and Fc gamma RII expression, respectively, and 1-oleoyl-2-acetylglycerol and N-(6-phenylhexyl)-5-chloro-1-naphthalenesulfonamide, both PK-C activators, did not show any apparent increase in Fc gamma R expression and phagocytosis. These results show that Fc gamma RI and Fc gamma RII expression on U937 cells is regulated by different mechanisms and that IFN-gamma and PMA play their roles in Fc gamma R expression and phagocytosis by different pathways. It is possible that cAMP but not PK-C plays an important role in the regulation of Fc gamma R expression and phagocytosis.

Antigens, Differentiation↗
PubMed1989

Differential regulation of the low affinity Fc receptor for IgE (Fc epsilon R2/CD23) and the IL-2 receptor (Tac/p55) on eosinophilic leukemia cell line (EoL-1 and EoL-3).

Two types of activation Ag, low affinity FcR for IgE (Fc epsilon R2)/CD23 and IL-2R (Tac/p55), were expressed and differently regulated on human eosinophilic leukemia cell lines (EoL-1 and EoL-3). Because the binding of IgE on EoL-3 cells was completely inhibited by H107 (anti-Fc epsilon R2/CD23 mAb) but not by irrelevant mAb, essentially all the low affinity Fc epsilon R2 on EoL-3 seemed to be the Fc epsilon R2/CD23 molecules. Both IL-4 and IFN-gamma enhanced the surface expression of Fc epsilon R2, whereas IL-1, IL-2, and IL-5 showed no effects, as determined by surface staining with anti-Fc epsilon R2 antibody (H107). In contrast to Fc epsilon R2 up-regulation, IL-4 and IFN-gamma showed a differential effect on the regulation of IL-2R (Tac/p55). Whereas IFN-gamma up-regulated the receptor expression of IL-2R/Tac, IL-4 did not. The result suggests that these lymphokines are involved in the different aspects of the activation pathway of the eosinophils. The possible role of Fc epsilon R2 and IL-2R on the function of eosinophils in allergic reaction is discussed.

Adjuvants, Immunologic↗
PubMed1989

Combined hepatitis B immune globulin and vaccine for postexposure prophylaxis of accidental hepatitis B virus infection in hemodialysis staff members: comparison with immune globulin without vaccine in historical controls.

Twenty-three staff members serving in a hemodialysis unit were exposed accidentally to needlestick contaminated with blood containing hepatitis B surface antigen and hepatitis B e antigen, as well as high levels of DNA polymerase activity (greater than 100 cpm). They received hepatitis B vaccine (20 micrograms) simultaneously with hepatitis B immune globulin (5 ml, 200 IU per ml) within 48 hr after the exposure, and the vaccination was repeated at 1 and 3 months. The protective efficacy was compared with that in a past study in the same unit in which 33 members were given hepatitis B immune globulin alone within 48 hr after the exposure to blood with similarly high levels of DNA polymerase activity. No differences were noted in age or sex between the staff members who were vaccinated and those who were not, nor were there any differences between their inocula in the titers of hepatitis B virus markers. During 12 months after the accident, only one (4%) of the 23 vaccinated members contracted hepatitis B virus infection, at a frequency significantly lower than 11 (33%) of the 33 members who did not receive vaccine (p less than 0.02). These results indicate that hepatitis B vaccine, when given in combination with hepatitis B immune globulin, is efficacious for postexposure immunoprophylaxis of accidental infection.

Adult↗
PubMed1989

DiGeorge syndrome with hypogammaglobulinaemia: a patient with excess suppressor T cell activity treated with fetal thymus transplantation.

A male infant with DiGeorge syndrome had hypogammaglobulinaemia with a normal number of B cells. CD3(+) T cells were reduced and the CD4(+)/CD8(+) ratio was reversed. Proliferative responses of T cells to mitogens and to allogeneic cells were low. The pokeweed mitogen (PWM)-induced B cell differentiation assay revealed a higher than normal suppressor T cell activity. This suggests that some T cells had differentiated into functionally mature cells resulting in an imbalance of regulatory T cell functions and that excess suppressor activity might play a role in hypogammaglobulinaemia. Fetal thymus transplantation improved both cellular and humoral immunity. The patient's susceptibility to viral and bacterial infections, proliferative response of T cells and serum Ig concentration returned to normal. The excess suppressor activity seen before transplantation disappeared. Hypocalcaemia did not improve. These results show that fetal thymus transplantation was effective not only in reconstituting cellular immunity but also in normalizing the imbalance of regulatory T cell functions in this patient with DiGeorge syndrome.

Agammaglobulinemia↗
PubMed1989

Regulation of Fc epsilon receptor 2 (CD23) expression on a human eosinophilic cell line EoL3 and a human monocytic cell line U937 by transforming growth factor beta.

Regulation of low-affinity receptors for IgE (Fc epsilon R2/CD23) on a human eosinophilic cell line EoL3 and a human monocytic cell line U937 was studied using an anti-Fc,R2/CD23 monoclonal antibody H107 by flow cytometry. While platelet-activating factor, interleukin 4, and interferon gamma significantly augmented Fc epsilon R2/CD23 expression on both cell lines, transforming growth factor beta (TGF beta) inhibited both the basal level of Fc epsilon R2/CD23 expression and the enhanced Fc epsilon R2/CD23 expression induced by these reagents in dose- and time-dependent manners. However, TGF beta did not significantly suppress the high basal level of Fc epsilon R2/CD23 expression on RPMI 8866 cells. These results suggest that Fc epsilon R2/CD23 expression on EoL3 and U937 cells is regulated by various cytokines and growth factors, and that TGF beta plays an important regulatory role in IgE-mediated immune responses.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1989

Interferon and (2'-5')oligoadenylate enhance the expression of low affinity receptors for IgE (Fc epsilon R2/CD23) on the human monoblast cell line U937.

The regulation of low affinity IgE receptor (Fc epsilon R2/CD23) expression on the human monoblast cell line U937 was examined by an anti-Fc epsilon R2/CD23 monoclonal antibody (H107) and the cDNA probe for Fc epsilon R2/CD23. Alpha interferon (IFN-alpha) and its intracellular mediator, (2'-5')oligoadenylate (2, 5-A), induced Fc epsilon R2/CD23 expression on U937 with no significant increase of the Fc epsilon R2/CD23 mRNA. PMA and IFN-gamma increased both surface Fc epsilon R2/CD23 expression and the Fc epsilon R2/CD23 mRNA levels. IFN-alpha effectively induced 2, 5-A synthetase activity in U937 cells, whereas IFN-gamma induced little. The results suggest that the mechanisms of enhancement of Fc epsilon R2/CD23 expression on U937 cells by IFN-alpha and IFN-gamma are different and that 2, 5-A may play an important role in the Fc epsilon R2/CD23 expression on U937 cells induced by IFN-alpha.

2',5'-Oligoadenylate Synthetase↗