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Biomedical subjects

A Fleer

Publications and source records attributed to A Fleer.

At least 73 records · Page 4Linked to original sources

Characterization of a proteinaceous adhesin of Staphylococcus epidermidis which mediates attachment to polystyrene.

Coagulase-negative staphylococci (CoNS) have evolved into important agents of foreign body-related infections. Adhesion of causative bacteria to biomaterials is considered to be an essential step in these infections. We and others have shown that adhesion of CoNS to biomaterials may be mediated by protease-sensitive surface constituents. In the present study we expanded on these investigations by characterizing a biomaterial adhesin of Staphylococcus epidermidis 354 by using a strain-specific monoclonal antibody (MAb 36.4). MAb 36.4 was strongly and exclusively reactive with strain 354 in an enzyme-linked immunosorbent assay in which whole bacteria were used as antigens. Immunoblotting of cell wall polypeptides of strain 354 revealed strong reactivity with a 200- to 220-kDa band and a weaker reaction in the 100- to 110-kDa range. Preincubation of strain 354 with MAb 36.4 resulted in a 54 to 91% (mean +/- standard deviation, 74% +/- 14%; n = 10) inhibition of adhesion to polystyrene spheres. Fab fragments prepared from MAb 36.4 also inhibited adhesion effectively, indicating specific blocking of an adhesion antigen rather than aspecific inhibition. Immunogold electron microscopy with MAb 36.4 revealed deposition of gold particles on the cell surface and possibly also on fimbrialike surface projections. It is concluded that a surface-located protein antigen of S. epidermidis 354 recognized by MAb 36.4 acts as an adhesin mediating attachment to uncoated foreign material. It is speculated that this type of adhesion to biomaterials may play an important role in the pathogenesis of foreign body-related infections caused by CoNS.

Antibodies, Monoclonal↗

[A child with pneumonia caused by a multiresistant pneumococcus].

Strains of Streptococcus pneumoniae resistant to penicillin have not previously been reported in The Netherlands. Now we have to report the isolation in November 1988 of a multiresistant pneumococcus (minimal inhibitory concentration 2 mg/l) from sputum of a three-year-old child from Poland. We advise isolating patients from abroad (Spain, Poland) in hospital and checking their bacteriological status to prevent introduction of penicillin resistant pneumococci into the Dutch population.

Child, Preschool↗

Surface proteins of coagulase-negative staphylococci: their role in adherence to biomaterials and in opsonization.

During the last decade coagulase-negative staphylococci (CN-Staph) have clearly emerged as pathogens in patients equipped with foreign devices. This has fueled the interest in these bacteria considerably and as a result, knowledge of the biology of CN-Staph as well as insight into the pathogenesis of biomaterial-associated infections due to these bacteria are rapidly expanding. Adherence of bacteria to biomaterials is a necessary step in the process of these infections. Evidence is accumulating that surface proteins of CN-Staph are essential in the early phases of adherence to biomaterials. By using monoclonal antibodies in immunoblotting and immune electron micrography we have identified a cell wall protein complex apparently located on the surface of CN-Staph and involved in adherence to biomaterials. Further studies will be oriented at characterization of the protein adhesin(s) and at identification of the surface structures with which the adhesion is associated.

Bacterial Adhesion↗

Deficiencies in opsonic defense to pneumococci in the human newborn despite adequate levels of complement and specific IgG antibodies.

We studied the major determinants of opsonophagocytosis against Streptococcus pneumoniae serotypes 14 and 19 in paired cord/maternal sera from 27 healthy term and 24 preterm infants in an attempt to gain more insight in the susceptibility of newborns to pneumococcal infection. For both pneumococcal serotypes studied, opsonic activity in neonatal sera varied greatly, but was moderately to profoundly deficient when compared to paired maternal sera, both in preterm (34.5 and 34.9% of the activity in maternal serum, for serotypes 14 and 19, respectively, p less than 0.001 for both) and in term serum (43.5 and 52.7% of the activity in maternal serum, for serotypes 14 and 19, respectively, p less than 0.001 for both). The opsonic deficiency in preterm sera could be ascribed to a diminished level of the major opsonins for pneumococci, i.e. complement factor C3 deposited on the bacterial surface (69.5 and 66.2% of C3 deposition in maternal serum on serotypes 14 and 19, respectively, p less than 0.01 for both) and specific anticapsular IgG antibodies (48.5 and 14.1% of maternal levels for serotypes 14 and 19, respectively, p less than 0.001 for both). However, the opsonic defect in serum from term infants could not be explained in a similar way, because C3 deposition and specific anticapsular IgG levels were equal to the values found in the paired maternal sera. Therefore, we conclude that the opsonic defect in newborn serum for pneumococci cannot be solely explained by a deficiency in the major opsonins for these bacteria. A dysfunction in these opsonins seems to be a more likely explanation for the observed opsonic defect in the neonate.

Antibodies, Bacterial↗

Pneumococcal septicemia in the newborn. A report on seven cases and a review of the literature.

This report summarizes the essential findings of seven cases of pneumococcal septicemia in the newborn and compares the data with those reported in the literature. It is emphasized that pneumococcal septicemia is a rare but highly lethal disease of the newborn. The clinical course strongly resembles early onset group B streptococcal disease. Epidemiological data suggest that the majority of infants are colonized near birth. Analogous to group B streptococcal sepsis, it seems rational to administer penicillin prophylaxis during labor to women with S. pneumoniae isolated from their genital tract to prevent vertical transmission and neonatal pneumococcal septicemia.

Female↗

[Cytokines].

Cytokines are relatively small polypeptides that are essential components of inflammatory reactions and immunologic processes. They are produced by a great variety of cells. The molecular biology revolution of the seventies and eighties has enabled investigators to elucidate the structure of cytokines and to unravel their spectrum of activity. Cytokines play a central role in the pathogenesis of infectious diseases and in the regulation of the immune system. Tumor necrosis factor (TNF) and interleukin-I (IL-I) were found to be responsible for most of the symptoms of infectious diseases, from fever to septic shock. In addition, TNF and IL-I are probably indispensable for repair of tissue damage. IL-2 is the pivotal cytokine for the regulation of the immune system; it is produced by CD4-positive T-cells and essential for the proliferation of T-lymphocytes in general and crucial for the induction of cytotoxic T-cells. Studies to define the therapeutic possibilities of cytokines are in progress.

Cytokines↗

Heterogeneity in opsonic requirements of Staphylococcus epidermidis: relative importance of surface hydrophobicity, capsules and slime.

The opsonic requirements of 65 strains of Staphylococcus epidermidis were compared in fresh and in heated normal human serum. The strains were isolated from patients with CAPD peritonitis (n = 26), neonatal septicaemia (n = 24) and nasal cultures (n = 15). A wide variation was observed in opsonic requirements between the different strains, both with fresh and with heated serum. Opsonization in heated serum proceeded less efficiently and higher concentrations (mean three-fold compared to fresh serum) were needed for adequate phagocytosis. However, a highly significant correlation was found between the minimal opsonic concentrations of fresh and of heated serum (r = 0.84, P less than 0.0005). In addition, S. epidermidis can become opsonized in agammaglobulinaemic serum. Thus, opsonization of S. epidermidis can be mediated by antibodies alone and by complement alone. Slime-producing strains and encapsulated strains did not require higher concentrations of serum to become opsonized. Opsonic requirements were highly significantly correlated with surface hydrophobicity. Enzymatic treatment rendered the strains more hydrophilic and decreased their opsonic requirements. Isolates from nasal cultures required significantly higher concentrations of both fresh and heated serum to become adequately phagocytozed, whereas isolates from CAPD peritonitis required higher concentrations of heated serum only compared to blood isolates. The uptake of S. epidermidis preopsonized in heated serum as determined in our direct phagocytosis assay did not result in a comparable chemiluminescence response.

Antibodies, Bacterial↗

Surface hydrophobicity and opsonic requirements of coagulase-negative staphylococci in suspension and adhering to a polymer substratum.

The opsonic requirements for phagocytosis in suspension of 38 clinical isolates of coagulase-negative staphylococci recovered from neonates with septicemia were found to be related to the degree of surface hydrophobicity of these strains. Sixteen isolates were adequately opsonized only in the presence of complement; this group was significant more hydrophobic (p less than 0.001) than the 22 strains not requiring complement for efficient uptake in suspension. Evidence showed that hydrophobic groups present on the bacterial surface may interfere with IgG opsonization. In contrast, IgG sufficed as an opsonin without complement being required for the efficient uptake of these hydrophobic strains when adhering to a polymer surface.

Bacterial Adhesion↗

Host defence to bacterial infection in the neonate.

Host defence to bacterial infection is mainly determined by opsonins, i.e., IgG antibodies and complement, and phagocytic cells, which co-operate to remove bacterial invaders from host tissues. Various studies have clearly documented distinct defects in both arms of host defence in the newborn period. Chemotaxis, i.e., directed migration of polymorphonuclear leukocytes (PMN) is impaired in the neonate. Phagocytosis of bacteria by neonatal PMN is normal, but post-phagocytic events, particularly metabolic activation and bacterial killing are impaired, the latter defect apparently due to diminished generation of reactive oxygen species. Both classical and alternative pathway activity of complement are mildly diminished (50-80% of adult values) in the term newborn, but are more severely decreased in the premature infant (20-40% of adult values in 28 to 36 weeks prematures). Opsonic activity of transplacentally-derived IgG when compared to maternal IgG is strikingly deficient against staphylococci and group B streptococci (GBS), in the latter case depending on the GBS serotype. Since opsonization is a key process in antibacterial defence, it is speculated that these opsonic defects of IgG may be an essential determinant of the neonate's susceptibility to disease due to these bacteria.

Bacterial Infections↗

Opsonisation and phagocytosis of group B meningococci by polymorphonuclear leucocytes: comparison of sulphonamide sensitive and resistant strains.

A large proportion of disease caused by sulphonamide resistant strains of group B type 15 meningococci affects patients 10-24 years. In contrast, disease caused by sulphonamide sensitive strains conforms to the usual pattern, and most infection occurs in early childhood. In an attempt to explain this phenomenon possible differences in susceptibility of resistant and sensitive strains to phagocytosis by polymorphonuclear leucocytes were investigated, using radioactively labelled bacteria. In initial experiments a group B resistant strain required higher concentrations of normal human serum and longer opsonisation times for phagocytosis than an ungroupable non-pathogenic meningococcus. Comparison of sulphonamide resistant and sensitive group B meningococci showed that with either heat inactivated serum or agammaglobulinaemic serum, phagocytosis did not occur with any of the strains, whereas if these two sera were used together, phagocytosis was restored to the level seen with normal human serum. Thus both antibody and complement are required for phagocytosis. Furthermore, opsonisation depended on an intact classical pathway of complement for each group B strain. In all the experiments there was no significant difference between the phagocytosis of sulphonamide sensitive and resistant group B strains neither with regard to the efficiency of opsonisation by normal human serum nor the exact requirements for antibody and complement.

Adolescent↗

[Cephalosporins: microbiological and pharmacokinetic properties, application to pediatrics].

Many cephalosporins are presently available for clinical use. Although the cephalosporins are excellent antimicrobial agents for many infectious diseases in childhood, they have not replaced the older antibiotic regiments. In fact they offer the pediatrician a broader range of choices in treatment. This article gives a review on microbiological and pharmacokinetic properties of cephalosporins and an indication for the use of cephalosporins in pediatric therapy.

Bacteria↗

Coagulase-negative staphylococci as nosocomial pathogens in neonates. The role of host defense, artificial devices, and bacterial hydrophobicity.

In contrast to the well-established pathogen Staphylococcus aureus, the coagulase-negative staphylococci--formerly collectively called Staphylococcus epidermidis--were until recently regarded as harmless commensals. During the last two decades, however, the coagulase-negative staphylococci have clearly emerged as pathogens in patients who have artificial devices implanted, such as prosthetic heart valves, hip prostheses, and cerebrospinal fluid shunts, and in those with compromised host defenses such as premature neonates, cancer patients, and transplant recipients. Recently, an increasing incidence of septicemia due to coagulase-negative staphylococci was detected in our neonatal intensive care unit. More than 90 percent of cases occurred in premature infants of low birth weight (less than 2,500 g). All septicemic infants were receiving intravenous therapy, and total parenteral nutrition solutions had been administered to nearly 80 percent just before or during the septic episode. This led us to examine the role of host defense factors in neonates and the possible significance of bacterial surface characteristics in the pathogenesis of catheter-associated infections.

Adhesiveness↗