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Biomedical subjects

B Heymer

Publications and source records attributed to B Heymer.

At least 109 records · Page 6Linked to original sources
PubMed1976

Detection of antibodies to bacterial cell wall peptidoglycan in human sera.

A radioimmunoassay has been developed for the measurement of antibodies to peptidoglycan in human sera including patients with rheumatic fever and juvenile rheumatoid arthritis. The assay is based on the percentage of binding of the hapten 125I-L-Ala-gamma-d-Glu-L-Lys-D-Ala-D-Ala, the major peptide determinant of peptidoglycan. Because of differences in the avidity of the antibodies in different sera, the amount of antibody was expressed as pentapeptide hapten-binding capacity (pentapeptide-HBC in ng/ml of serum). Fourteen out of 105 normal blood donors had a pentapeptide-HBC value greater than or equal to 75 ng/ml serum. Values in healthy children 5 to 18 years of age were less than or equal to 50 ng/ml. Sixty-eight percent of the individuals with rheumatic fever had values greater than or equal to 75 ng/ml, an indication that streptococcal infections can stimulate an immune response to peptidoglycan. Thirty-five percent of the patients with juvenile rheumatoid arthritis had values greater than or equal to 75 ng/ml. Such a finding points to a possible association between bacterial infections and juvenile rheumatoid arthritis.

Acute Disease↗
PubMed1975

Morphological and immunological characteristics of Streptococcus pyogenes, group A, type 50.

Streptococcus pyogenes, group A, type 50, in contrast to other group A streptococci, causes spontaneous disease in mice thereby providing a suitable experimental model for the study of human streptococcosis. Type 50 possesses various peculiar morphological and immunobiological characteristics and under certain conditions forms and extremely thick non-antigenic capsule which seems to interfere with the binding of antibody. This interference is most likely responsible for the difficulties in detecting type 50 streptococci in the tissues of infected mice by immunofluorescent staining. Whereas the surface components (hyaluronic acid, M-antigen) of the type 50 Streptococcus exhibit several uncommon features, the more deeply located cell wall antigens, like peptidoglycan and C-carbohydrate, do not differ in either their chemical constituents or their serological reactions from the comparable components of other group A streptococci.

Animals↗
PubMed1975

[Biological activity of bacterial peptidoglycan (mucopeptide) (author's transl)].

A brief survey on the ultrastructure, the chemical composition and the immunological properties of bacterial cell wall peptidoglycan (mucopeptide) is presented. This paper deals with the various recently discovered biological activities of peptidoglycan. These could be divided into three different groups, namely: 1. Endotoxin-like properties: pyrogenicity, induction of the local Shwartzman reaction, increase in non-specific resistance to bacterial infection, release of 5-hydroxytryptamine from rabbit platelets, complement activation,gelation of amebocyte lysate. 2. Inflammatory reactions of skin and internal organs, aggressin activity (virulence factor), inhibition of phagocytosis of bacteria by granulocytes and macrophages, inhibition of growth of cell cultures, cytotoxity to granulocytes and macrophages. 3. Potentiation of humoral and cellular immune responses (adjuvant), enhancement of tumor defense in experimental animals. The potential mechanisms of action of peptidoglycan are discussed and attention is focused on the implications of the various peptidoglycan activities for medicine.

Amino Acid Sequence↗
PubMed1975

Animal experimental studies on chronic granulomatous inflammation and T-lymphocyte-system.

The presence of lymphocytes in chronic granulomatous inflammations is frequently thought to indicate that thymus-dependent cellular immune mechanisms are involved in the pathogenesis of such processes. Therefore, in the present studies, a model of a granulomatous heaptitis (induced by heat-inactivated group A streptococci) was used to determine whether liver granulomata, consisting of macrophages and lymphocytes, could also be evoked in neonatally thymectomized or in congenitally thymus-deficient nude mice. The morphological (light and electron microscopical, immunohistological) investigations were supplemented with selective determination of T- and B-lymphocyte function. The thymus-deficient mice, after injection of streptococci, developed liver granulomata that did differ neither quanlitatively nor quantitatively from those of control animals with thymus. Lymphocytes were found within the granulomata in both animal groups. There was no evidence for functional disorder of the RES in thymus-deficient mice; on the contrary, RES-activity seemed to be increased. Phagocytosis of streptococci, their intracellular breakdown and streptococcal antigen-degradation occurred as fast or faster in such animals. PHA- and LPS-stimulation of spleen lymphocytes indicated a considerable depletion of T-cells in neonatally thymectomized mice and a complete absence of T-cells in congenitally thymus-deficient nude mice. However, radioimmunological determination of antibodies to group A streptococcal carbohydrate revealed that both groups of experimental animals possessed functionally active B-cells. Therefore, the granulomatous hepatitis described here can be defined as a focal reaction of the liver RES with "B-lymphocyte trapping". Cellular immune mechanisms are not involved in the pathogenesis of these lesions.

Animals↗
PubMed1975

Antibodies to peptidoglycan in the sera from population surveys.

A recently described latex agglutination test was used to determine peptidoglycan antibody titers in sera from healthy human subjects and in sera from patients with a history of streptococcal infections or rheumatoid arthritis. Using latex particles coated with group A streptococcal peptidoglycan 32.8% of the sera from 961 healthy donors reacted positively with titers ranging from 1 : 5 to 1 : 320. Peptidoglycan antibodies were more frequently present in the younger population (45.1% in the 20-29 years old) and considerably decreased in advanced age (15.7% in the 70 years or older). Sera from 82 patients with elevated ASO-titers showed detectable peptidoglycan antibody levels in 40.2%; a statistically significant correlation between ASO and peptidoglycan antibody titers could not be substantiated. Sera from 25 patients with rheumatoid arthritis gave a high incidence (56-92%) of positive results. However there was evidence that this may be due to the action of rheumatoid factor present in such sera.

Adolescent↗
PubMed1975

Biological properties of the peptidoglycan.

This review deals with those biological activities of peptidoglycan that are not directly analogous to the properties of gram-negative bacterial endotoxin. The report is divided into 3 major parts: 1. A survey of peptidoglycan activities such as the induction of inflammatory skin reactions, lesion-enhancing activity (virulence factor), inhibition of phagocytosis of bacteria, inhibition of cell migration, cytotoxicity to mammalian cells, potentiation of the humoral and cellular immune response (adjuvant activity) and enhancement of tumor defense in experimental animals. 2. A presentation of factors which may influence these biological activities of peptidoglycan. 3. A brief discussion of the potential mechanisms of action of peptidoglycan.

Adjuvants, Immunologic↗
PubMed1975

Use of limulus assay to compare the biological activity of peptidoglycan and endotoxin.

The gelation of a lysate prepared from the amebocytes of Limulus polyphemus, the horseshoe crab, has been used to detect endotoxin-like material in clinical studies and in "in vitro" experiments. The investigation of blood samples from 54 hospitalized patients suspected of having endotoxemia, revealed a positive limulus test in 14. Infections due to gram-positive organisms were not associated with positive assays. These results were in agreement with the observation that living gram-positive microorganisms - in contrast to gram-negative bacteria - did not initiate lysate gelation when studied "in vitro". Only very high concentrations of peptidoglycan, isolated from the cell walls of various gram-positive bacteria, induced the reaction. Therefore, these findings support the view, that the limulus test is relatively specific for the detection of gram-negative bacterial endotoxin and endotoxemia.

Animals↗
PubMed1975

Migration inhibition of peritoneal macrophages by peptidoglycan.

Previous studies have shown that peptidoglycans from group A and B streptococci inhibit the migration of peritoneal exudate cells from non-sensitized rats and guinea pigs. In the present studies peptidoglycans from S. aureus and S. epidermidis were found to inhibit the migration of cells to the same extent as group A streptococcal peptidoglycan. In contrast, HSA-pentapeptide, an immunologically active synthetic analog of the peptide moiety of peptidoglycan which is free of the intrinsic toxicity of naturally occurring peptidoglycans, did not induce migration inhibition of peritoneal exudate cells from non-sensitized guinea pigs. Sensitization of animals with 200 mug HSA-pentapeptide emulsified in incomplete Freund's adjuvant significantly reduced the inhibitory effect of streptococcal and staphylococcal peptidoglycan; HSA-pentapeptide again showed no activity. However, when HSA-pentapeptide was tested against cells from animals sensitized with 200 mug HSA-pentapeptide incorporated in complete Freund's adjuvant, a strong inhibition of migration was evident. Skin tests performed in these animals, in contrast to the dermonecrotic reaction elicited by streptococcal or staphylococcal peptidoglycan, revealed a characteristic delay hypersensitivity to HSA-pentapeptide.

Animals↗
PubMed1975

Adjuvancy of streptococcal nucleic acids.

A study was performed to find out whether or not RNA and DNA isolated from Group A streptococcal cytoplasm does possess adjuvant activity. The findings obtained indicate that the adjuvancy of streptococcal RNA is very similar to that of poly I:C. The adjuvant activity of poly I:C is characterized by its capacity to increase the number of pre-existing hemolysin-producing spleen cells and by its ability to increase the development of 19S and 7S producers early in the 12-day-period of primary immune response. The adjuvancy of streptococcal DNA was considerably less pronounced than that of RNA. Neither poly I:C nor streptococcal RNA and DNA were found to be capable of increasing the process of priming for the secondary immune response.

Adjuvants, Immunologic↗
PubMed1975

Purification and characterization of a Streptomyces albus endo-N-acetylmuramidase lytic for group A and other beta haemolytic streptococci.

The purification and characterization of the streptolytic exo-enzyme from the Maxted-McCarty strain of Streptomyces albus is described. This enzyme was shown to be an endo-N-acetylmuramidase with a molecular weight of 10 to 12,000 and optimal activity at pH 8 and 45 degrees C. The enzyme is lytic for streptococci of various groups, Micrococcus lysodeikticus, Staphylococcus aureus, as well as Escherichia coli. It closely resembles the F1 endo-N-acetylmuramidase described by Ghuysen et al. (1966) except for small differences in the products of lysis of streptococcal cell walls and the resistance of Escherichia coli to lysis by the F1 enzyme. Lysates of group A and A variant streptococcal cell walls prepared with purified Streptomyces albus muramidase contained serologically active M protein and C carbohydrate-peptidoglycan complexes. The chemical and immunological characteristics of these enzymmatic products of streptococcal cell walls are reported and their utility as immunologic reagents is described.

Bacterial Proteins↗
PubMed1975

A radioactive hapten-binding assay for measuring antibodies to the pentapeptide determinant of peptidoglycan.

A major portion of the humoral immune response to peptidoglycans is directed against the non-cross-linked pentapeptide side chains of these ubiquitous bacterial antigens. At present, no specific and sensitive assay for pentapeptide antibody determination is available. Therefore, a radioimmunoassay has been developed which employs the synthetic pentapeptide hapten L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala, labeled by the active ester method of Bolton and Hunter to high specific activities (6.74 to 18.18 muCi/mug) with 125I, and used as a reagent for measuring pentapeptide antibody. A-variant streptococcal antisera, known to contain pentapeptide antibodies as shown by quantitative precipitation, would bind more than 95% of the radiolabeled hapten in contrast to 2 to 3% by preimmune rabbit sera. Specificity of the binding reaction was demonstrated by inhibition experiments imploying various synthetic oligopeptides related or unrelated to the pentapeptide in the radioimmunoassay. Binding curves established with serial dilutions of peptidoglycan antiserum were linear from 15 to 500 mug/ml of antibody permitting pentapeptide antibody measurement within this range. Comparative data on pentapeptide antibody determinations by quantitative precipitation and radioimmunoassay are given and the time course of the production of this antibody in 14 rabbits hyperimmunized with A-variant streptococcal vaccine is reported.

Ammonium Sulfate↗
PubMed1975

Measurement of peptidoglycan antibodies by a radioimmunoassay.

Staphylococcus epidermidis peptidoglycans solubilized by sonication or lysozyme digestion, and synthetic peptidoglycan analogs such as HSA-carboxymethyl-Gly-L-Ala-L-Ala-D-Ala-D-Ala (HSA-pentapeptide) or L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala (pentapeptide) have been labeled with 125I and tested for their applicability in the radioactive antigen binding assay. Use of radioiodinated Staph. epidermidis peptidoglycans was found to be considerably impeded by the presence of at least 2 different antigenic sites on such molecules, the pentapeptide and the glycan determinant. Application of labeled HSA-pentapeptide was limited by the necessity to use PEG for precipitation of Ag-Ab-complexes and by short linear potions of binding curves. However, the synthetic pentapeptide hapten, radioiodinated by the active ester method of BOLTON and HUNTER, proved to be a most useful regent for the selective measurement of pentapeptide antibody. Inhibition studies indicated that the immunological specificity of the labeled hapten was retained. Pentapeptide binding curves were linear from 15-500 g/ml of antibody. Generally, there was good agreement between pentapeptide antibody concentrations measured by radioimmunoassay and quantitative precipitation.

Antibodies↗