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Biomedical subjects

D Schmeling

Publications and source records attributed to D Schmeling.

16 recordsLinked to original sources
PubMed1987

Prenatal diagnosis of trisomy 20 mosaicism indicating an extra embryonic origin.

An additional case of amniotic fluid trisomy 20 mosaicism is presented. After careful counselling, the pregnancy continued and a phenotypically normal female was delivered. This case of amniocyte mosaicism establishes the source of aneuploid cell line as amnion. Since an extra-embryonic origin of the mosaicism has been confirmed, this should be carefully considered as a real possibility in counselling such families.

Chromosomes, Human, Pair 20↗
PubMed1983

Antibiotic-induced modification of Bacteroides fragilis and its susceptibility to phagocytosis by human polymorphonuclear leukocytes.

Bacteroides fragilis grown in the presence of sub-inhibitory concentrations of clindamycin was shown to be altered its degree of encapsulation and susceptibility to phagocytosis by human polymorphonuclear leukocytes. Little polysaccharide capsule could be demonstrated either by light or transmission electron microscopy when the bacteria were grown anaerobically for four hours in the presence of 1/2 MIC of clindamycin. Such clindamycin-grown cells could be opsonized by normal human serum, and although less complement was consumed in the process, were more effectively taken up by the leukocytes than bacteria grown in the absence of the drug (45% versus 24%). It was also shown that drug treatment caused significant cellular leakage in the presence of serum, the 3H-label appearing extracellularly. In addition there was greater loss of viability of the bacterial cells grown in the presence of the drug and subsequently exposed to the leukocytes for 60 min.

Bacteroides fragilis↗
PubMed1981

Phagocytosis, bacterial killing, and metabolism by purified human lung phagocytes.

Phagocytic and bactericidal activities of purified polymorphonuclear neutrophils (PMNs), monocytes (MNs), or alveolar macrophages (AMs) from the same individuals for Staphylococcus aureus strain 502A or Escherichia coli strain ON2 were compared in vitro. Factors that may influence these activities were evaluated. The bactericidal activity of S. aureus and E. coli of PMNs was greater than that of MNs or AMs. Two factors were identified that may account for this result. (1) The rate of phagocytosis of opsonized S. aureus and E. coli was greater by PMNs. (2) The nonmitochondrial oxygen burst after nonparticulate stimulation was much greater by PMNs. Qualitative differences in opsonic requirements for ingestion of S. aureus by PMNs, MNs, and AMs were also identified. In contrast to PMNs or MNs, phagocytosis of S. aureus by AMs was not opsonin-dependent. The results suggest that mononuclear phagocytes may adapt their opsonic requirements to facilitate uptake of S. aureus. Despite this adaptation, their bactericidal capability remains limited when compared with PMNs.

Escherichia coli↗
PubMed1981

Potentiation of opsonization and phagocytosis of Streptococcus pyogenes following growth in the presence of clindamycin.

Streptococcus pyogenes, bearing M-protein on its surface, resists opsonization by normal human serum and subsequent phagocytosis by human polymorphonuclear leukocytes. Previous studies have shown that M-protein positive organisms are poorly opsonized by the alternate pathway of complement. In an attempt to define further the role of the surface components of S. pyogenes in this process, we examined the ability of clindamycin, an antibiotic that inhibits protein biosynthesis, to alter bacterial opsonization. An M-protein positive strain of S. pyogenes was grown in varying concentrations of clindamycin at levels lower than those which inhibited growth, i.e., at levels less than the minimal inhibitory concentration. These bacteria were incubated with purified human polymorphonuclear leukocytes and peripheral blood monocytes. Significant enhancement of bacterial opsonization, phagocytosis, and killing resulted. Measurement of complement consumption and binding of the third component of complement (C3) onto the bacterial surface demonstrated that organisms grown in the presence of clindamycin activated complement more readily and fixed more C3 on their surface. Electron microscopy revealed the probable basis for these findings. Streptococci exposed to clindamycin during growth were largely denuded of surface "fuzz," the hairlike structures bearing M-protein. We conclude that the incorporation of clindamycin at concentrations that fail to inhibit growth of S. pyogenes nevertheless causes significant changes in the capacity of these bacteria to resist opsonization by serum complement. These findings support the hypothesis that M-protein inhibits bacterial opsonization by interfering with effective complement activation on the bacterial surface.

Antigens, Bacterial↗
PubMed1980

Opsonization of four Bacteroides species: role of the classical complement pathway and immunoglobulin.

Previous investigators have suggested that opsonization of two Bacteroides species is mediated exclusively by the alternative complement pathway and requires immunoglobulins. In this study, the nature of the opsonic factors in nonimmune human serum for four species of Bacteroides was investigated by measuring uptake of [(3)H]thymidine-labeled bacteria by human polymorphonuclear leukocytes. Normal human serum, C2-deficient serum, immunoglobulin-deficient serum, and serum chelated with ethylene glycol-bis(beta-aminoethyl ether)-N,N-tetraacetic acid (EGTA), MgEGTA, and ethylenediaminetetraacetic acid (EDTA) were used as opsonic sources. Heat inactivation of each of these sera significantly reduced its opsonic activity for all four Bacteroides species, suggesting that serum complement was essential for effective opsonization. All strains were opsonized in the absence of the classical complement pathway; however, kinetics studies revealed that opsonization proceeded at a significantly faster rate when the classical complement pathway was intact. Although two strains were opsonized in immunoglobulin-deficient sera, opsonization was less efficient and appeared to occur via the alternative complement pathway. Unexpectedly, all strains were well opsonized by the classical complement pathway in 10% serum which had been effectively chelated with EGTA or EDTA. The explanation for this finding is unknown; however, it is possible that cell wall cations of Bacteroides species may participate in the activation of complement in chelated serum, resulting in effective opsonization. It was also found that Bacteroides, when incubated with an Escherichia coli strain in normal serum, could compete for opsonins and thereby reduce phagocytosis of E. coli. It is possible that competition for opsonins among bacterial species contributes to the synergistic role these organisms share in mixed floral infections.

Bacteroides↗
PubMed1979

Inhibition of alternative complement pathway opsonization by group A streptococcal M protein.

Group A streptococcal M protein is known to be antiphagocytic; however, the exact basis for this property has not been established. In this study the hypothesis was tested that cell wall--associated M protein inhibits phagocytosis by interfering with bacterial opsonization. Two strains of group A Streptococcus pyogenes, CS44 (M+) and CS64 (an M- variant of CS44), were radiolabeled, and after incubation in serum these organisms were exposed to human polymorphonuclear leukocytes. Phagocytosis was quantitated by measurement of leukocyte-associated radioactivity. The contributions of complement and of immunoglobulin to streptococcal opsonization were evaluated by use of serum from a variety of sources. The results revealed that the M- strain was efficiently opsonized via the alternative complement pathway in a relative absence of immunoglobulins. In contrast, the M+ strain was poorly opsonized by all sera tested. These findings suggest that streptococcal M protein in some way prevents bacterial opsonization via the alternative complement pathway and that this property of M protein may partly explain its antiphagocytic characteristic.

Antigens, Bacterial↗
PubMed1978

Influence of encapsulation on staphylococcal opsonization and phagocytosis by human polymorphonuclear leukocytes.

In previous studies, encapsulated Staphylococcus aureus strains have been shown to resist phagocytosis. In this investigation, the nature of the interference with phagocytosis by human polymorphonuclear leukocytes was examined by studying the opsonization of two pairs of unencapsulated (Smith compact and M variant) and encapsulated (Smith diffuse and M) S. aureus strains. The uptake of [3H]glycine-labeled bacteria by normal leukocytes was quantitatively measured after incubation of bacteria in pooled serum, C2-deficient serum, immunoglobulin-deficient serum, and serum from a rabbit immunized with S. aureus M. The presence of a capsule was found to interfere with opsonization by both the classical and alternative pathways of complement as well as by heat-stable opsonic factors in nonimmune human serum. This interference was significantly greater in the case of the S. aureus M strain than in the case of the Smith diffuse strain. The only effective opsonic source for S. aureus M was immune rabbit serum. It is proposed that encapsulation of S. aureus strains interferes with phagocytosis by preventing effective bacterial opsonization.

Antibodies, Bacterial↗
PubMed1978

Dichotomy between opsonization and serum complement activation by encapsulated staphylococci.

Previous studies have demonstrated that encapsulated Staphylococcus aureus strains are not effectively opsonized by the serum complement system. Encapsulated staphylococci thereby "resist phagocytosis." To test whether this phenomenon might be explained by an inability of encapsulated strains to activate complement, the relationship between staphylococcal opsonization and serum complement activation was studied. Although encapsulation was found to interfere with opsonization by pooled human serum (human polymorphonuclear leukocytes phagocytized significantly fewer encapsulated bacteria than unencapsulated bacteria after incubation in this opsonic source), encapsulated (S. aureus M and Smith diffuse) and unencapsulated (S. aureus M variant and Smith compact) strains had similar capacities for complement activation as measured by C3-C9 consumption. When C2-deficient and immunoglobulin-deficient sera were studied, again C3-C9 consumption was not influenced by the presence or absence of a capsule. In addition, C3 was detected on the surface of both S. aureus M and M variant strains after incubation in pooled serum and staining with fluorescein-conjugated anti-C3 antibody. Thus, encapsulated staphylococci are not effectively opsonized even though complement is activated and C3 is present on the bacterial surface. The exact mechanism by which the capsule interferes with opsonization is still not known; however, inhibition of complement activation appears not to be the explanation of this phenomenon.

Antibodies↗
PubMed1978

The key role of peptidoglycan in the opsonization of Staphylococcus aureus.

In an effort to determine the staphylococcal cell surface component(s) of importance in opsonization, cell walls (peptidoglycan and teichoic acid) and peptidoglycan were isolated from Staphylococcus aureus strain H grown in [3H]glycine-containing broth. After incubation of the cell walls and peptidoglycan with various opsonic sources, uptake by human polymorphonuclear leukocytes was measured. The opsonic requirements for phagocytosis of cell walls and peptidoglycan were found to be similar to those of intact bacteria. Removal of teichoic acid from the cell wall did not affect opsonization. Likewise, a teichoic acid-deficient mutant strain of S. aureus H was opsonized in a manner similar to that of the parent strain. Immunoglobulin G functioned as the major heat-stable opsonic factor and both the classical and alternative pathways participated in opsonization. Kinetic studies revealed that opsonization of peptidoglycan, as well as C3-C9 consumption by peptidoglycan, proceeded at a slower rate via the alternative pathway (C2-deficient serum) than when the classical pathway was present (normal serum). The ability of peptidoglycan to activate C3-C9 was significantly reduced when normal and C2-deficient sera were preabsorbed with peptidoglycan at 2 degrees C suggesting that antibodies to peptidoglycan may be involved in activation of both the classical and alternative complement pathways. Thus, peptidoglycan appears to be the key cell wall component involved in staphylococcal opsonization, and it is suggested that host response to peptidoglycan, a major cell wall component of most gram-positive bacteria, may be related to the development of "natural immunity" to this group of microorganisms.

Cell Wall↗
PubMed1978

Complement-mediated phagocytosis of Pseudomonas aeruginosa.

The nature of the opsonic factors in nonimmune human serum for six blood culture isolates of Pseudomonas aeruginosa was investigated by measuring uptake of [3H] adenine-labeled bacteria by human PMNs. Normal human serum, C2- and C4-deficient sera, zymosan-treated serum, and immunoglobulin-deficient sera were used as opsonic sources. Heat inactivation of each of these serum sources markedly reduced its opsonic capacity for all Pseudomonas strains, suggesting that the serum C system was essential for opsonization. Five strains were opsonized in the absence of the classical C pathway; however, kinetic studies revealed that opsonization proceeded at a faster rate when the classical pathway was present. In spite of markedly reduced factor B and C3 levels, zymosan-treated serum retained significant opsonic activity for one of the strains tested. Four strains were poorly opsonized by immunoglobulin-deficient serum, and C activation by these strains appeared to depend upon the presence of antibodies. Two strains, however, were effectively opsonized in a relative absence of antibodies. Thus, in the nonimmune state, phagocytosis of P. aeruginosa is mediated primarily via the C system, and antibodies appear to play a role in the opsonization of some but perhaps not all Pseudomonas strains.

Complement Factor B↗
PubMed1977

Kinetics of phagocytosis and bacterial killing by human polymorphonuclear leukocytes and monocytes.

The kinetics of phagocytosis and bacterial killing by normal human polymorphonuclear leukocytes (PMNLs) and by monocytes (MNs) were compared by use of [3H]thymidine-labeled Staphylococcus aureus, Escherichia coli, and Listeria monocytogenes. The rate of phagocytosis by PMNLs was approximately twice that by MNs for all three bacterial species. Although a marked difference was found in opsonic requirements for phagocytosis of S. aureus, E. coli, and L. monocytogenes, phagocytosis by PMNLs and MNs was mediated via the same serum factors. All three species were killed rapidly once they were associated with leukocytes; however, the rate of killing by MNs was slower than that of PMNLs. The slower rate of killing appeared to be secondary to slower ingestion of attached bacteria by MNs. Thus, PMNLs and MNs appear to possess receptors with specificity for the same bacterial opsonins; however, PMNLs are capable of more efficienct bacterial phagocytosis (attachment and ingestion) than are MNs.

Escherichia coli↗
PubMed1977

Effect of antibiotics of chemotaxis of human leukocytes.

The effect of 20 different antibiotics on chemotaxis by human neutrophils was studied. Human leukocytes incubated with chloramphenicol, rifampin, sodium fusidate, and tetracyclines in vitro showed markedly depressed migration. The mechanisms by which these antibiotics affect leukotaxis are discussed.

Anti-Bacterial Agents↗
PubMed1977

Quantitative phagocytosis by human polymorphonuclear leucocytes. Use of radiolabelled emulsions to measure thae rate of phagocytosis.

A new micro-method for the quantitative measurement of phagocytosis by neutrophils is described. The material used for phagocytosis consists of a radioactive oil emulsion coated with E. coli lipopolysaccharide. Uptake of radioactive material is a function of cell number, duration of incubation, dilution of serum used for opsonization, content of lipopolysaccharide and concentration of emulsion. This method can be used to quantify rapidly and precisely phagocytosis rates of as few as 5 x 10(4)-10(6) polymorphonuclear leucocytes and the opsonic activity of 10 microliter serum.

Albumins↗