IgE-mediated systemic reactions to gelatin included in the varicella vaccine.
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Anaphylaxis↗
Biomedical subjects
S Inouye
Publications and source records attributed to S Inouye.
Gelatin-specific humoral and cellular immune responses in children with immediate- and nonimmediate-type reactions to live measles, mumps, rubella, and varicella vaccines.
BACKGROUND: This study was designed to investigate the development of both cellular and humoral immune responses to gelatin in patients with vaccine-related immediate and nonimmediate reactions. Our purpose was to define the nature of the responses in the different clinical states. METHODS: Six patients with immediate reactions and 21 patients with nonimmediate reactions after inoculation of various live vaccines were studied. Measurement of gelatin-specific IgE was performed in all subjects. Gelatin-specific T-cell responses detected by an in vitro lymphocyte proliferation assay and by an assay for IL-2 responsiveness were investigated to compare the immune response in patients with the two types of reaction. RESULTS: All six patients with immediate reactions had IgE responses to gelatin, whereas none of the 21 patients with nonimmediate reactions had any anti-gelatin IgE. All of the six patients with immediate reactions and 17 of the 21 patients with nonimmediate reactions exhibited positive T-lymphocyte responses specific to gelatin. CONCLUSIONS: Immediate and nonimmediate reactions are caused by different types of allergy to gelatin, and cell-mediated immunity to gelatin may play an important role in the pathogenesis of nonimmediate reactions.
Antibodies, Viral↗
Systemic immediate-type reactions to gelatin included in Japanese encephalitis vaccines.
Three children had systemic immediate-type reactions to Japanese encephalitis (JE) vaccine which contains gelatin as a stabilizer. We found that all the children had anti-gelatin IgE in their sera. Further, two of the three also had experienced systemic allergic reactions to gelatin-containing foods before the vaccination. We assume that the systemic allergic reactions to JE vaccines might be caused by gelatin in the JE vaccine.
Anaphylaxis↗
Epitope specificity of IgE antibodies to a major allergen (Cry j 1) of Japanese cedar pollen in sera of humans and monkeys with pollinosis.
Japanese cedar (Cryptomeria japonica) pollinosis has been reported to occur naturally in Japanese monkeys (Macaca fuscata) as well as humans. Using monoclonal antibodies (mAb) specific to Cry j 1, a major allergen in Japanese cedar pollen, we identified five independent epitopes (EP-1 to EP-5) on the molecule. The epitopes recognized by IgE antibodies in the sera of humans and monkeys with the pollinosis were analysed by an IgE enzyme-linked immunosorbent assay inhibition method with these mAb. In human patients, the mAb to EP-1 strongly blocked the binding of IgE antibodies in all patients' sera to Cry j 1. The reaction patterns of IgE antibodies in monkeys, however, varied among the troops of monkeys. In some troops, the mAb to EP-1 showed a blocking pattern similar to that for human patients. In other troops, mAb to EP-4 and EP-5 blocked binding of IgE. These results indicate that some, but not all, monkeys have antibody responses to the major allergen similar to those of humans.
Allergens↗
Pkn9, a Ser/Thr protein kinase involved in the development of Myxococcus xanthus.
The Myxococcus xanthus gene, pkn9, encodes a protein that contains significant homology with eukaryotic Ser/Thr protein kinases. The pkn9 gene was singled out of a previously identified family of kinase genes by amplification techniques that displayed differences in kinase gene expression during selected periods of the M. xanthus life cycle. Pkn9 was constitutively expressed during vegetative growth and upregulated during the aggregation stage of early development. It consists of 589 amino acids, and its N-terminal 394 residues show 38% identity with both Pkn1 and Pkn2 of M. xanthus. This region also shows 29, 25 and 29% identify with myosin light-chain kinase, protein kinase C, and cAMP-dependent protein kinase, respectively. A 22-residue hydrophobic transmembrane domain separates the kinase domain from the 173-residue C-terminal domain that resides on the outside of the inner membrane. The C-terminal domain contains two sets of tandem repeats of 13 and 10 residues which have no known function. When expressed in Escherichia coli under the T7 promoter, Pkn9 was found to be phosphorylated on serine and threonine residues. Disruption of the pkn9 kinase catalytic subdomains I-III by the insertion of a kanamycin-resistance gene resulted in slightly delayed, smaller and more-crowded fruiting bodies, while spore formation was normal. Total deletion of the pkn9 gene caused severely reduced progression through development resulting in light loose mounds that become slightly more compact over time. Development progressed further at the centre than at the edge of the spot, and spore formation was significantly reduced. Two-dimensional gel analysis revealed that both the disruption and the deletion of pkn9 prevented the expression of five membrane proteins (KREP9-1-4). These results suggest that the loss of Pkn9 kinase activity caused altered fruiting-body formation, the absence of the KREP9 proteins in the membrane, and reduced spore production.
Amino Acid Sequence↗
Interleukin-4 production in Epstein-Barr virus-transformed B cell lines from peripheral mononuclear cells of patients with atopic dermatitis.
Interleukin-4 (IL-4) is known as an immunomodulatory cytokine secreted by relatively few cell types, for example, activated T lymphocytes, basophils, and mast cells, but not by B cells. It plays an important role in promoting the production of the IgE antibody. We established Epstein-Barr virus (EBV)-positive B cell lines from peripheral blood mononuclear cells of patients with atopic dermatitis (AD) and tested the production of several cytokines in the cell lines. We found that IL-4 was produced in a cell line, OB, by an IL-4-specific enzyme-linked immunosorbent assay. IL-4 mRNA was detected in OB and two other AD-derived cell lines by IL-4-specific reverse transcription-polymerase chain reaction. IgE was also produced by the OB cells. The production of IL-4 and IgE was enhanced in the cells treated with 12-O-tetradecanoyl phorbol-13-acetate. This is the first evidence that IL-4 is produced by an EBV-transformed B cell line.
B-Lymphocytes↗
The in-vivo activity of an antifungal antibiotic, benanomicin A, in comparison with amphotericin B and fluconazole.
The in-vivo antifungal activity of benanomicin A administered intravenously or subcutaneously was compared with that of amphotericin B and fluconazole using animal models of systemic infections with Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans. The efficacy of benanomicin A in C. albicans infection was more pronounced when administered in multiple doses than in a single dose. This was also true of fluconazole, but not of amphotericin B, which showed no difference between single and multiple dosings. Benanomcin A eradicated C. albicans cells from the kidneys of infected mice in a manner comparable to that of amphotericin B, but more effectively than fluconazole. The histopathological findings obtained from the kidneys of the C. albicans-infected mice confirmed the therapeutic efficacy of benanomicin A. The subcutaneous ED50 values of benanomicin A were 1.30 mg/kg/day (C. albicans) and 19.0 mg/kg/day (A. fumigatus) which were intermediate between those of amphotericin B and fluconazole in the two models. The subcutaneous ED50 value of benanomicin A for C. neoformans was 21.5 mg/kg/day, which was higher than that of amphotericin B.
Amphotericin B↗
msDNA-Ec48, the smallest multicopy single-stranded DNA from Escherichia coli.
Previously we have reported a novel bacterial reverse transcriptase (RT) from Escherichia coli ECOR58 strains in which the YXDD box was replaced with LVDD (J.-R. Mao, S. Inouye, and M. Inouye, Biochem. Biophys. Res. Commun. 227:489-493, 1996). Here we determined the structure of the multicopy single-stranded DNA (msDNA) produced by the RT. The msDNA was found to consist of a single-stranded DNA of 48 nucleotides in length, the shortest msDNA thus far identified from natural sources. The msDNA, the RT, and the retron are designated msDNA-Ec48, RT-Ec48, and retron-Ec48, respectively. On the basis of the structure of the msr gene, the RNA molecule of msDNA-Ec48 is predicted to be composed of 119 ribonucleotides; it is the longest RNA among the known msDNAs. Analysis of the DNA sequences flanking the retron indicates that retron-Ec48 is associated with a prophage related to phages P2 and P4.
Amino Acid Sequence↗
Differentiation of primary from nonprimary genital herpes infections by a herpes simplex virus-specific immunoglobulin G avidity assay.
An immunoglobulin G (IgG) antibody avidity assay which uses protein-denaturing agents and a modification of an enzyme-linked immunosorbent assay have been investigated for their usefulness in distinguishing primary genital herpes simplex virus (HSV) infections from nonprimary infections. Forty-nine serum specimens from patients with primary, recurrent, and nonprimary first-episode genital herpes were studied. The clearest separation was obtained with 6 M urea treatment, giving mean avidity indices of 0.398 for sera < or = 100 days after the infection and 0.879 for sera > 100 days after the infection (P < 0.001). No significant difference in avidity indices was observed between the recurrent and nonprimary first-episode infections. Determination of the avidity of HSV-specific IgG will improve the diagnostic potential of HSV serology.
Antibodies, Viral↗
Responses of monkeys with pollinosis to two major allergens of Japanese cedar pollen.
We examined the responses of two Japanese monkeys with pollinosis to two major allergens (Cry j 1 and Cry j 2) of Japanese cedar pollen. The two monkeys (A and B) had specific IgE antibodies to the allergens and showed a strong positive reaction to both of them in the intradermal test. In the histamine release test with peripheral blood mononuclear cells (PBMC), monkey A showed a typical pattern similar to that seen in human patients, while monkey B released a low level of histamine. The proliferative response of PBMC to both allergens in monkey A was weak, but was typical in monkey B. From clinical as well as immunological points of view, these monkeys may be a suitable animal model for Japanese cedar pollinosis in humans.
Allergens↗
Cladinose analogues of sixteen-membered macrolide antibiotics. IV. Improved therapeutic effects of 4-O-acyl-L-cladinose analogues of sixteen-membered macrolide antibiotics.
Six derivatives of sixteen-membered macrolides possessing 4-O-acyl-alpha-L-cladinose as a neutral sugar were synthesized via 3"-methylthiomethyl ether intermediates in reasonable yield. Introduction of a methyl group on the 3"-hydroxyl group of midecamycin A1 was effective for enhancing its antibacterial activity. All these derivatives exhibited excellent therapeutic effects in mice, and some of them showed improved pharmacokinetics compared with the natural antibiotics (mycarose type) in mice. Facile synthesis of 9-O-acylated analogues are also described.
Animals↗
Cladinose analogues of sixteen-membered macrolide antibiotics. V. Preparation of unsubstituted L-cladinose analogues: effect of methylation of a 3"-hydroxyl group on the bioactivity.
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Anti-Bacterial Agents↗
Correlation of susceptibility and resistance of twenty-five bacterial strains by analysis of MIC database of cephalosporins and oxacephalosporins.
MIC database of 1,407 cephalosporins and oxacephalosporins was utilized to characterize 25 bacterial strains including Gram-positive and Gram-negative bacteria. MIC values were converted to activity rank indices, and distribution patterns of these indices were compared among the bacterial strains. Salmonella enteritidis. No. 11 was the most susceptible bacterium, and the activity against this strain was ascribed to the binding of beta-lactams to the PBPs without any significant barrier to the approach of beta-lactams. Twenty-one strains were assumed to have similar types of PBPs to those of S. enteritidis No. 11 in the binding profile to beta-lactams. Comparison of the scatter diagrams of the activity rank indices revealed two different types of resistances arising from beta-lactamases (9 strains) and outer membrane permeability and/or active efflux (15 strains). The resistance factor arising from beta-lactamase was affected by the nature of the C-3 substituents of beta-lactams.
Bacteria↗
Correlation of susceptibility and resistance of twenty-five bacterial strains by analysis of MIC database of cephalosporins and oxacephalosporins
MIC database of 1,407 cephalosporins and oxacephalosporins was utilized to characterize 25 bacterial strains including Gram-positive and Gram-negative bacteria. MIC values were converted to activity rank indices, and distribution patterns of these indices were compared among the bacterial strains. Salmonella enteritidis No. 11 was the most susceptible bacterium, and the activity against this strain was ascribed to the binding of beta-lactams to the PBPs without any significant barrier to the approach of beta-lactams. Twenty-one strains were assumed to have similar types of PBPs to those of S. enteritidis No. 11 in the binding profile to beta-lactams. Comparison of the scatter diagrams of the activity rank indices revealed two different types of resistances arising from beta-lactamases (9 strains) and outer membrane permeability and/or active efflux (15 strains). The resistance factor arising from beta-lactamase was affected by the nature of the C-3 substituents of beta-lactams.
Journal Article↗
Positive-negative KG cassettes for construction of multi-gene deletions using a single drug marker.
Positive-negative KG cassettes were developed in order to create a number of independent deletion mutations on the bacterial chromosome using a single drug marker. These cassettes consist of a kanamycin-resistant (KmR) gene for positive screening and a galactokinase gene (galK) for negative screening. Both genes are in an operon driven by the native KmR promoter and are flanked by identical fragments of yeast chromosomal DNA approximately one kb in size. An internal region of a cloned target gene of a bacterium is replaced with a cassette, which is then transformed into the bacterium. The intact gene on the chromosome is replaced with the mutated gene by homologous recombination. From the KmR cells thus obtained, those cells which lose both KmR and galK genes by homologous recombination between the identical yeast DNA fragments are subsequently screened on plates containing 2-deoxygalactose, a non-metabolizable analogue of galactose. This method was applied to isolate a triple-deletion mutant of pkn3, pkn1, and pkn11 from Myxococcus xanthus.
Anti-Bacterial Agents↗
Chemical nature of the light emitter of the Aequorea green fluorescent protein.
The jellyfish Aequorea victoria possesses in the margin of its umbrella a green fluorescent protein (GFP, 27 kDa) that serves as the ultimate light emitter in the bioluminescence reaction of the animal. The protein is made up of 238 amino acid residues in a single polypeptide chain and produces a greenish fluorescence (lambda max = 508 nm) when irradiated with long ultraviolet light. The fluorescence is due to the presence of a chromophore consisting of an imidazolone ring, formed by a post-translational modification of the tripeptide -Ser65-Tyr66-Gly67-. GFP has been used extensively as a reporter protein for monitoring gene expression in eukaryotic and prokaryotic cells, but relatively little is known about the chemical mechanism by which fluorescence is produced. To obtain a better understanding of this problem, we studied a peptide fragment of GFP bearing the chromophore and a synthetic model compound of the chromophore. The results indicate that the GFP chromophore consists of an imidazolone ring structure and that the light emitter is the singlet excited state of the phenolate anion of the chromophore. Further, the light emission is highly dependent on the microenvironment around the chromophore and that inhibition of isomerization of the exo-methylene double bond of the chromophore accounts for its efficient light emission.
Amino Acid Sequence↗
Enhancement of frame-shift mutation by the overproduction of msDNA in Escherichia coli.
A minor population of wild Escherichia coli strains contain retroelements called retrons, which produce a peculiar satellite DNA, multicopy single-stranded DNA (msDNA). It has been reported that mismatched base pairs in the secondary structure formed in msDNA are mutagenic in E. coli[Maas et al.(1994) Mol.Microbiol. 14,437-441; Maas et al. (1996) Mol. Microbiol, 19, 505-509]. We reexamined this proposal by converting mismatched base pairs to matched base pairs using a single msDNA species, msDNA-Ec86, or by deleting mismatched regions using msDNA-Ec73. We also examined the effect of reverse transcriptases (RT) without msDNA production on mutagenesis. All the constructs are under the lpp/lac promoter-operator control so that their mutagenic effects can be tested in the absence and the presence of a lac inducer. It was found that when the production of msDNA-Ec86 or Ec73 was induced, reversion frequencies from Lac- to Lac+ significantly increased in the case of a Lac- mutation caused by a frame-shift mutation, but much less by a substitution mutation. The removal of mismatched base pairs eliminated the high mutation frequencies, and the inducible expression of RT alone was not mutagenic. These results are consistent with the hypothesis of Maas and his associates that mismatched base pairs in msDNA sequester a cellular mismatch repair system, resulting in the increase of frame-shift mutations.
Base Composition↗
An unusual bacterial reverse transcriptase having LVDD in the YXDD box from Escherichia coli.
A minor population of wild strains of Escherichia coli contains a gene for reverse transcriptase (RT) which is responsible for the synthesis of multicopy single-stranded DNA (msDNA), a branched DNA-RNA complex. A DNA fragment capable of synthesizing msDNA was cloned from strain ECOR-58, one of the 72 wild strains in the ECOR collection. The complete open reading frame of a novel reverse transcriptase, designated ECOR-58 RT, was identified. ECOR-58 RT consisted of 408 amino acid residues, and its 227-residue polymerase domain from residue 43 to 269 showed significant homologies to all the other bacterial RTs so far identified. Most significantly, its YXDD box, the most highly conserved sequence in all RTs from prokaryotes to eukaryotes, was found to be replaced with LVDD. ECOR-58 RT was found to be most distantly related in a phylogenetic tree to all 9 other bacterial RTs so far identified.
Amino Acid Sequence↗