Search PubMed⌕ Search

Biomedical subjects

H van Dijk

Publications and source records attributed to H van Dijk.

At least 19 recordsLinked to original sources
PubMed1997

Inhibition of human complement by beta-glycyrrhetinic acid.

Licorice, the root extract of Glycyrrhiza glabra I., is used as a medicine for various diseases. Anti-inflammatory as well as anti-allergic activities have been attributed to one of its main constituents, glycyrrhizin. These activities are mainly ascribed to the action of the aglycone, beta-glycyrrhetinic acid. beta-Glycyrrhetinic acid has a steroid-like structure and is believed to have immunomodulatory properties. To determine whether interference with complement functions may contribute to the immunomodulatory activity of beta-glycyrrhetinic acid, its effects on the classical and alternative activation pathways of human complement were investigated. We found that beta-glycyrrhetinic acid is a potent inhibitor of the classical complement pathway (IC50 = 35 microM), whereas no inhibitory activity was observed towards the alternative pathway (IC50 > 2500 microM). The anticomplementary activity of beta-glycyrrhetinic acid was dependent on its conformation, since the alpha-form was not active. It was also established that naturally occurring steroids, e.g. hydrocortisone and cortisone, did not inhibit human complement activity under similar conditions. Detailed mechanistic studies revealed that beta-glycyrrhetinic acid acts at the level of complement component C2.

Administration, Topical↗
PubMed1996

Molecular characterization of the BRO beta-lactamase of Moraxella (Branhamella) catarrhalis.

A rapid increase in the prevalence of beta-lactamase-producing Moraxella (Branhamella) catarrhalis strains has been noticed during the last decades. Today, more than 80% of strains isolated worldwide produce beta-lactamase. To investigate beta-lactamase(s) of M. catarrhalis at the molecular level, the BRO-1 beta-lactamase gene (bla) was isolated as part of a 4,223-bp HindIII fragment. Sequence analysis indicated that bla encodes a polypeptide of 314 amino acid residues. Insertional inactivation of bla in M. catarrhalis resulted in complete abrogation of beta-lactamase production and ampicillin resistance, demonstrating that bla is solely responsible for beta-lactam resistance. Comparison with other beta-lactamases suggested that M. catarrhalis beta-lactamase is a unique enzyme with conserved residues at the active sites. The presence of a signal sequence for lipoproteins suggested that it is lipid modified at its N terminus. In keeping with this assumption was the observation that 10% of beta-lactamase activity was found in the membrane compartment of M. catarrhalis. M. catarrhalis strains produce two types of beta-lactamase, BRO-1 and BRO-2, which differ in their isoelectric points. The BRO-1 and BRO-2 genes from two ATCC strains of M. catarrhalis were sequenced, and only one amino acid difference was found between the predicted products. However, there was a 21-bp deletion in the promoter region of the BRO-2 gene, possibly explaining the lower level of production of BRO-2. The G + C content of bla (31%) was significantly lower than those of the flanking genes (47 and 50%), and the overall G + C content of the M. catarrhalis genome (41%). These results indicate that bla was acquired by horizontal gene transfer from another, still unknown species.

Amino Acid Sequence↗
PubMed1996

A new procedure for the purification of streptococcal pyrogenic exotoxin A from Streptococcus pyogenes supernatant.

An important role in the pathogenesis of invasive group A streptococcal disease has been ascribed to the production of streptococcal pyrogenic exotoxin A. We present a new technique for the purification of streptococcal pyrogenic exotoxin A from Streptococcus pyogenes NY-5 supernate, which is highly efficient with respect to yield (35%), purity (> or = 99%), and time.

Bacterial Proteins↗
PubMed1996

Ultrastructural organization and regulation of a biomaterial adhesin of Staphylococcus epidermidis.

Coagulase-negative staphylococci have emerged as important pathogens in infections associated with intravascular devices. Microbial adherence to biomaterial surfaces is a crucial step in the pathogenesis of these infections. Staphylococcal surface proteins (herein referred to as SSP-1 and SSP-2) are involved in the attachment of Staphylococcus epidermidis 354 to polystyrene. In the present study we show that the adhesin protrudes from the cell surface as a fimbria-like polymer. Furthermore, in vitro proteolytic cleavage of SSP-1 produces an SSP-2-like protein which coincides with a loss of adhesive function. SSP-1 expression is down-regulated in a phenotypical variant of S. epidermidis 354 whereas SSP-2 expression is not. These results could suggest that proteolytic cleavage is a key to the regulation of the adhesive state of S. epidermidis in vivo.

Adhesins, Bacterial↗
PubMed1995

Complement resistance is a virulence factor of Branhamella (Moraxella) catarrhalis.

The purpose of this study was to investigate complement resistance in Branhamella (Moraxella) catarrhalis isolated from healthy schoolchildren or sputum-producing adult patients. Two techniques were used: a serum bactericidal assay as the gold standard and an easier 'culture and spot' test. Children (age 4-13; n = 303) and patients (n = 1047) showed high colonization/infection rates with B. catarrhalis (31% and 19%, respectively). Complement resistance or intermediate sensitivity occurred frequently in patient isolates (62% and 27%, respectively) and less often in children (33% and 8.5%, respectively; P << 0.0001). In young children (age 4-5 years), the proportion of complement-resistant strains was around 50%. Complement resistance in B. catarrhalis is associated with illness and may hence be considered a virulence factor.

Adolescent↗
PubMed1995

Deficient antipneumococcal polysaccharide responses in HIV-seropositive patients.

In a prospective study, serological responses and opsonic activity towards Streptococcus pneumoniae were measured in 60 HIV-infected patients and 25 controls after the administration of the 23-valent pneumococcal vaccine (PneumovaxR). Serum samples were collected before vaccination and at weeks 1, 2, 4, and 12 after vaccination and were tested for the presence of antibodies against a mixture of capsular polysaccharide antigens (pool) and against type 3 and type 4 antigens (PS3 and PS4), using an ELISA. A serological response was defined as a two-fold or greater increase in serum titer after vaccination. Opsonophagocytosis was measured in patients with a definite response against PS3. Generally, prevaccination antipneumococcal antibody titers were clearly higher in HIV-infected patients than in healthy controls. After vaccination, antipool antibody responses were found in 76% of vaccinated patients; 24% of the patients were non-responders. In patients with more than 0.300 x 10(9) CD4 + cells per liter the percentage of responders was 94%; in patients with fewer than 0.300 x 10(9) CD4 + cells per liter this percentage was 68% (P < 0.05). The antipool response in control subjects was 92%. A serological response to PS3 and PS4 was found in 29% and 49% of the patients, respectively, and was correlated with CD4 + cell count. In controls, these percentages were 48% and 92%, respectively. In 30% of responding patients, antibody titers dropped already to prevaccination levels by week 12 after vaccination. Opsonophagocytosis was not significantly improved by vaccination, probably because of a relatively high preexisting opsonic activity. Although prevaccination conditions may have had an important influence on the study outcome, the results are not in favor of a significant beneficial effect of vaccination with PneumovaxR on antibody formation in HIV-infected patients. This raises further questions as to the relevance of pneumococcal vaccination in this population.

Antibodies, Bacterial↗
PubMed1995

Phenotypic characterization of epidemic versus sporadic strains of methicillin-resistant Staphylococcus aureus.

Forty strains of methicillin-resistant Staphylococcus aureus (MRSA) were divided on the basis of their epidemiologic behavior into two subgroups, sporadic MRSA (SMRSA) and epidemic MRSA (EMRSA) strains. The strains were examined for binding of 125I-labelled fibronectin, vitronectin, collagen, Fc fragments of immunoglobulin G, and fibrinogen. A significant difference between EMRSA and SMRSA strains was found for binding of 125I-labelled fibrinogen and for Fc fragments of immunoglobulin G, (P < 0.05). No significant difference in the binding of 125I-labelled fibronectin and collagen was found between EMRSA and SMRSA strains. The binding of 125I-labelled vitronectin to MRSA strains was found to be aspecific. Capsular serotypes of the strains were determined with monoclonal antibodies against capsular types 5 and 8. Strains could be divided into the following four groups: types 5, 8, and 5/8 and nontypeable. More nontypeable strains were found in the EMRSA group (66.6%). Significantly more EMRSA strains (79%) than SMRSA strains (44%) produced alpha-toxin (P < 0.025). Logistic regression analysis using a combination of the parameters 125I-labelled immunoglobulin G binding, capsular type, and alpha-toxin production predicted the epidemic character with a sensitivity of 83% and a specificity of 75%.

Bacterial Toxins↗
PubMed1994

Experimental evidence for Moraxella-induced penicillin neutralization in pneumococcal pneumonia.

Resistance of microorganisms to antimicrobial agents is an increasing problem in the treatment of infectious diseases. In mixed infections, an interesting development can arise when one organism protects another from being killed by an antibiotic. Unfortunately, in the case of respiratory tract infections, experimental evidence of this development is poor. In this study, mice intranasally infected with a lethal number of pneumococci and treated with a curative dose of penicillin or amoxicillin died from pneumococcal pneumonia when they were coinoculated with beta-lactamase-producing Moraxella catarrhalis. beta-lactamase-negative M. catarrhalis did not show a similar indirect pathogenic effect. Treatment with a combination of amoxicillin and the beta-lactamase inhibitor clavulanic acid was not affected by beta-lactamase-producing M. catarrhalis. These findings help explain antibiotic failure in respiratory tract infections, even though the causative microorganism is sensitive to the antibiotic in vitro.

Amoxicillin↗
PubMed1994

Protective effects of orally administered, Klebsiella-containing bacterial lysates in mice.

The efficacy, as oral vaccines, of hepta- and mono-valent, Klebsiella-containing bacterial lysates and a number of control preparations was tested in mice. The preparations were administered during two periods of four days each, interrupted by an interval of 3 days. Fourteen days after the first dose, the animals were challenged either intraperitoneally (i.p.; peritonitis/sepsis model) or intranasally (i.n.; pneumonia model). Animals treated with low doses of Klebsiella lysate, in the form of either a 7-valent lysate or a Klebsiella monolysate, showed enhanced survival in both the peritonitis/sepsis and the pneumonia models. Hexa- and tetra-valent preparations without Klebsiella were not protective in the models tested. Furthermore, it was found that the protection is accompanied by priming for Klebsiella-specific IgG responsiveness (probably at the T cell level) and by significant IgA anti-Klebsiella serum antibody levels in about one third of the animals. The oral efficacy of Klebsiella-containing lysates suggests the presence of an adjacent component that directs Klebsiella antigen(s) to follow a selective intestinal pathway which renders them immunogenic. The identity of this component is under investigation.

Administration, Oral↗
PubMed1994

Differences in complement activation between complement-resistant and complement-sensitive Moraxella (Branhamella) catarrhalis strains occur at the level of membrane attack complex formation.

The mechanism of resistance to human complement-mediated killing in Moraxella catarrhalis was studied by comparing different complement-sensitive and complement-resistant M. catarrhalis strains in a functional bystander hemolysis assay and an enzyme-linked immunosorbent assay (ELISA) for soluble terminal complement complexes. Complement-resistant stains appeared to activate complement to the same extent as, or even slightly better than, complement-sensitive strains. This indicates that complement-resistant strains do not inhibit classical or alternative pathway activation but interfere with complement at the level of membrane attack complex formation. A clear difference in dose-response curves for resistant and sensitive strains was observed both in the bystander hemolysis assay and in the ELISA. Complement-resistant strains showed optimum curves, whereas complement-sensitive strains gave almost linear curves. We conclude that resistant strains bind and/or inactivate one of the terminal complement components or intermediates involved in membrane attack complex formation. Trypsin, known to abolish complement resistance, changed the optimum dose-response curve of a resistant strain to a linear one, which strongly suggests that complement resistance is mediated by an M. catarrhalis-associated protein. This protein acts directly or through the binding of a terminal complement inhibitor present in serum.

Bacterial Proteins↗
PubMed1993

Peptidoglycan and teichoic acid from Staphylococcus epidermidis stimulate human monocytes to release tumour necrosis factor-alpha, interleukin-1 beta and interleukin-6.

Cytokines play a major role in the pathophysiology of septic shock. In this study, human peripheral blood monocytes were stimulated with peptidoglycan and teichoic acid, purified from a strain of Staphylococcus epidermidis. Polymyxin B (PM-B) was added to avoid the effects of possible contamination with endotoxin. Tumour necrosis factor-alpha (TNF), interleukin-1 beta (IL-1), and interleukin-6 (IL-6) in the supernates were measured by enzyme-linked immunosorbent assays. Peptidoglycan and teichoic acid induced TNF, IL-1, and IL-6 in a concentration-dependent manner. Teichoic acid was a weaker inducer than peptidoglycan, especially for IL-1. Lipopolysaccharide from an E. coli strain was used as a control, being 100-1000 times more potent than peptidoglycan and teichoic acid.

Enzyme-Linked Immunosorbent Assay↗
PubMed1993

Bacterium-induced autoimmune reactivity.

Evidence is growing that autoimmune reactivity results from a combination of endogenous (e.g. MHC type) and environmental factors. Our experimental study focuses on the induction of autoimmune reactivity by microbial factors. Splenic formation and serum levels of anti-erythrocyte antibodies and circulating immune complexes were taken as parameters. It was found that experimental infection of mice with Escherichia coli and Salmonella typhimurium was accompanied by clear signs of autoimmune reactivity, smooth bacteria being almost ten times as potent as rough mutant strains. An attempt was made to correlate the data obtained with live bacteria to their corresponding endotoxins. It was concluded that the induction of more prominent autoimmune reactivity by smooth bacteria must be ascribed to a longer survival time in vivo. Our data support the view that bacterium-derived factors are involved in the etiology (and possibly also the course) of autoimmune diseases.

Animals↗
PubMed1992

Rapid isolation of human complement component C9 to verify the specificity of a haemolytic C9 microassay.

A sensitive, haemolytic microassay of human complement component C9 was developed. The assay is based on the principle of reactive (C5b6-initiated) haemolysis and uses commercially available C9-depleted serum as reagent for C9. The specificity of the assay was verified by rapid, activity-guided isolation of the haemolytic component from human serum using high-performance liquid chromatography (HPLC) on a system for fast protein liquid chromatography. This isolation yielded a single component with characteristics of C9. The results suggest that rapid, activity-guided isolation as a new application of HPLC can be a useful tool to demonstrate the specificity of a functional assay.

Adult↗
PubMed1992

C1-inhibitor prevents PEG fractionation-induced, EDTA-resistant activation of mouse complement.

Fractionation of mouse serum by precipitation with a critical amount of polyethylene glycol 6000 (PEG; 11% w/v) results in a classical and alternative pathway-independent activation of the terminal complement route. The activation can take place after the separation of an activating principle together with the terminal route components from a natural regulator. The isolation and identification of the regulatory component preventing this activation in serum, is subject of this paper. The regulator was purified by fractionated PEG-precipitation (15-25%), followed by heparin-Sepharose affinity, Mono Q anion-exchange, and Superose 12 gel filtration chromatography. The regulator appeared to be a single-chain protein with a Mr of 96 k. A protein with similar activity purified from human serum had a Mr of 104 k and was functionally and antigenically indistinguishable from C1-INH. The mouse 96 k protein inhibited C1-esterase activity indicating that this protein is indeed C1-INH. Mouse C1-INH regulates the PEG fractionation-induced bypass activation of complement, but does not interfere with the assembly or the lytic activity of membrane attack complexes. alpha 2-Macroglobulin appeared also to be capable of inhibiting the PEG-precipitation-induced activation process, but with lower efficiency.

Animals↗
PubMed1992

Anti-inflammatory activity of gallic acid.

Gallic acid was found to possess antiinflammatory activity towards zymosan-induced acute food pad swelling in mice. In vitro studies on the mode of action of gallic acid revealed that this compound interferes with the functioning of polymorphonuclear leukocytes (PMNs). Scavenging of superoxide anions, inhibition of myeloperoxidase release and activity as well as a possible interference with the assembly of active NADPH-oxidase may account for the inhibition of inflammatory process by gallic acid. Structure-activity relationship analysis showed that the o-dihydroxy group of gallic acid is important for the inhibitory activity in vitro.

Animals↗