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Biomedical subjects

H Ohkuni

Publications and source records attributed to H Ohkuni.

At least 55 records · Page 3Linked to original sources

Efficacy of acellular pertussis vaccine in Japan--comparison of two areas, one area where immunization started at 6 months and the other area at over 2 years of age--Regional Surveillance Committee on Tuberculosis and Infectious Diseases of Osaka.

In the Osaka area, a very satisfactory surveillance system of infectious diseases has been achieved with the establishment of a weekly facsimile network, and computer aided graphics and feedback system. A mathematical formula has been devised for calculating the number of reported cases in exactly 100,000 of the population using the constant reported number of cases of exanthema subitum every week. With this method, we compared the incidence of pertussis patients in two areas, one where acellular pertussis vaccine is given to children after 6 months of age and the other where it is given at more than 2 years of age. The former area has the one fifth the incidence of pertussis patients of the latter.

Age Factors↗

Coronary arteritis in mice after systemic injection of bacterial cell wall peptidoglycan.

We examined cell wall peptidoglycan (PGL) derived from group A streptococcus and other bacteria for possible induction of coronary arteritis in mouse strains. The histological finding of the main trunk of the coronary arteries of BALB/c, DBA/1J, C57BL/6 and DBA/2 mice, which were given an intravenous injection of sonicated PGL fragments of st. pyogenes at 500 micrograms per mouse 4 times at intervals of 1 week, showed diffuse cellular infiltration in the vascular wall as well as perivascular space. Marked hyperplasia of the endothelial cells was noted and necrosis of the medial smooth muscle of the coronary artery also was observed. The elastica stain clearly demonstrated fragmentation and degeneration of the elastic fibers. The histological change of the originating site of the aorta also noted swelling or hyperplasia of the endothelial cells and perivascular cellular infiltration. PGL fragments of st. mutans, st. sanguis and s. aureus did not cause any heart lesions. Coronary arteritis induced by st. pyogenes PGL could be very useful as an experimental animal model of Kawasaki's disease.

Animals↗

Acute joint inflammation in mice after systemic injection of the cell wall, its peptidoglycan, and chemically defined peptidoglycan subunits from various bacteria.

The systemic injection of an aqueous suspension of cell wall or its peptidoglycan (PG)-rich sonicate derived from group A streptococcus and Lactobacillus casei induced acute joint lesions in BALB/c, DBA/1J, (BALB/c X DBA/1J)F1, and C3H/He mouse strains, but not in C57BL/6, DBA/2, and AKR strains. Cell walls and their enzymatically degraded PG fragments from other bacteria as well as the synthetic disaccharide dipeptide and Lactobacillus plantarum cell wall-derived disaccharide tripeptide produced similar acute inflammation in susceptible BALB/c mice. Acute swelling and erythema of the ankles and wrists were observed as early as 3 h, reached maximum severity by day 2, and generally subsided by days 4 to 6 after injection. Histological studies showed synovial proliferation, marked infiltration of many mononuclear cells and a few polymorphonuclear leukocytes in the soft tissues, and extensive deposition of fibrinous exudate in the joint space. Antibody response was detectable against the PG fraction. However, anti-PG antibody does not seem to be responsible for the pathogenesis of this disease. On the other hand, experiments on decomplementation by cobra venom factor suggest that complement components are involved in the early phase of this arthritic model.

Animals↗

Immunological studies of post-streptococcal sequelae. Evidence for presence of streptococcal antigens in circulating immune complexes.

Since elevated levels of circulating complexes have been noted to occur in the sera of patients with post-streptococcal sequelae, the possibility that these complexes contained streptococcal antigens within the complex was investigated. Sera from these patients were precipitated with polyethylene glycol to extract a fraction rich in these complexes, which was then injected into rabbits. The rabbit sera were then reacted with both cellular and extracellular fractions obtained from streptococcal strains associated with either acute post-streptococcal nephritis (APSGN) or acute rheumatic fever (ARF) by using immunoelectrophoresis and ELISA techniques. The data demonstrate that both ARF and APSGN complexes contain streptococcal antigens. However, APSGN complexes react uniquely to certain extracellular antigens present in those strains associated with nephritis, while ARF complexes react specifically to certain streptococcal extracellular antigens excreted by strains associated with rheumatic fever. Neither of the two groups of complexes appear to contain streptococcal antigens related to any cellular antigens derived from the group A streptococcus. Additionally, a rabbit serum immunized with streptococcal extracellular products reacted directly with complexes isolated from nephritis patients. Removal of the gamma globulin by absorption with an anti-human Fc serum resulted in the concomitant loss of reactivity with the anti-streptococcal serum, strongly suggesting an intimate association of the streptococcal antigen with these complexes. The presence of streptococcal antigens within the circulating immune complex of patients with APSGN coupled with their specific presence in those strains associated with post-streptococcal glomerulonephritis argues strongly for a causal role of these antigens in the disease process.

Antibodies, Bacterial↗

Studies on the antigenicity of glucagon.

In order to test the safety of glucagon (GG), the immunogenicity of GG was studied in rabbits and guinea pigs. Any sensitization, as revealed by anaphylactic shock, Arthus reaction, passive cutaneous anaphylaxis (PCA) or radioimmunoassay, was not demonstrated in animals immunized with GG alone. The anti-GG antibodies were detected by PCA and radioimmunoassay in two of the five animals immunized with GG mixed with Freund's complete adjuvant. Anti-GG IgE antibody production in mice was found in one of the ten mice given 570 micrograms and three of the six mice given 1,000 micrograms of GG with aluminum hydroxide gel (Alum), but other doses of GG with Alum produced no IgE antibody. These results indicate that the antigenicity of GG is very weak.

Anaphylaxis↗

Immunological studies of post-streptococcal sequelae: serological studies with an extracellular protein associated with nephritogenic streptococci.

Using the Ouchterlony double diffusion and the crossed-immunoelectrophoresis techniques the reactivity to a purified extracellular product of nephritogenic group A streptococci (NASP) was examined with both acute and convalescent sera obtained from patients with documented post-streptococcal glomerulonephritis and patients with documented acute rheumatic fever. The streptococcal antigen utilized in these studies was first purified on SDS gels and then eluted from the gel, resulting in a single protein band on SDS electrophoresis. Double diffusion studies revealed that only nephritis patients reacted to this extracellular product associated with nephritogenic strains, whereas rheumatic fever sera produced no line of precipitation. An assay of serial bleedings from nephritis patients suggested that the antibody reactive to the NASP was in higher titre in the acute phase of the disease and decreased with convalescence. In confirmation of these findings, crossed-immunoelectrophoresis experiments were conducted with a battery of sera from acute nephritic and non-nephritic patients against the NASP antigen. A striking increase was detected in the reactivity of nephritis patients (96%) compared to non-nephritis sera (15-20%). Comparison between acute and convalescent sera using this technique confirmed the finding of decreasing antibody titre with resolution of disease. These findings of a specific humoral response in patients with acute post-streptococcal nephritis to the NASP of nephritogenic strains further implicates an aetiological function to this protein.

Adolescent↗

An HLA-linked immune suppression gene in man.

Genetic control of immune response in man was investigated with the system of antigen-specific T cell proliferation in vitro against streptococcal cell wall (SCW) antigen. Family analysis by Morton's maximum likelihood scoring method revealed that the low response to SCW antigen was controlled by a single dominant gene. Furthermore, this gene was shown to be closely linked to HLA (lod score was 3,209 at theta = 0). This is the first description of the HLA-linked immune suppression gene in man. The possible mechanism for this gene action was discussed.

Adult↗

Adjuvant activities in production of reaginic antibody by bacterial cell wall peptidoglycan or synthetic N-acetylmuramyl dipeptides in mice.

This paper is concerned with the adjuvant activity in stimulatory immunoglobulin E production against ovalbumin (OA) by bacterial cell walls, cell wall peptidoglycan (PG), and their PG fragments and synthetic N-acetylmuramyl (MurNAc) dipeptides in A/J mice. A PG isolated from Streptococcus pyogenes, PG subunit polymer and dimer obtained from Staphylococcus epidermidis, and water-soluble fragments of cell walls or PG prepared from Nocardia corynebacteriodes and Streptomyces gardneri were found to enhance both the primary and secondary responses of anti-OA immunoglobulin E antibody production. It was suggested that the PG portion, either intact or highly degraded, was capable of enhancing the immunoglobulin E antibody production, and there was no need for the non-PG moiety or intactness of PG structure for the adjuvant activity. This finding was confirmed and extended by the use of synthetic MurNAc dipeptides. Among eight MurNAc dipeptides tested, MurNAc-l-Ala-d-isoGln, MurNAc-l-Ala-d-Gln, MurNAc-l-Ala-d-Glu, and MurNAc-l-Ser-d-isoGln were found active as an adjuvant in the stimulation of the primary and secondary reaginic anti-OA antibody production in a similar way to the cell wall PG and their fragments. None of the synthetic MurNAc-l-Ala-l-isoGln, MurNAc-l-Ala-l-Gln, MurNAc-l-Ala-l-Glu, and MurNAc-l-Ala-d-isoAsn, on the other hand, stimulated the anti-OA immunoglobulin E antibody production in either primary or secondary response, indicating the importance for the adjuvancy in immunoglobulin E production of the configuration of the glutamic acid residues adjacent to the l-Ala (or l-Ser) in muramyl dipeptides.

Acetylmuramyl-Alanyl-Isoglutamine↗

Increased capillary permeability in guinea pigs and rats by peptidoglycan fraction extracted from Group A streptococcal cell walls.

The increased capillary permeability in the skin of guinea pigs and rats was induced by peptidoglycan fraction (PG fraction) extracted from cell walls of group A streptococcus, but not by C-carbohydrate of streptococcal cell walls nor lipopolysaccharide of Escherichia coli and Salmonella abortus. The increased capillary permeability caused by PG fraction was also observed in germ-free rats. It was suggested that the increased capillary permeability for PG fraction might be due to the biological activity of PG fraction. The pattern of the reaction of increased capillary permeability consists of two phases: the leakage of the dye in the first phase appeared immediately after the intracutaneous injection of PG fraction, and the second phase seems to depend upon vasculitis. The increasing activity of capillary permeability to PG fraction may play an important role in inducing initial change of tissue injury by streptococcal cell walls.

Animals↗