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Biomedical subjects

R van Furth

Publications and source records attributed to R van Furth.

At least 127 records · Page 7Linked to original sources
PubMed1991

CD14 contributes to the adherence of human monocytes to cytokine-stimulated endothelial cells.

Monocyte adherence to endothelial cells (EC) is selectively increased during inflammation. The mechanisms underlying monocyte-EC interaction indicated the involvement of surface-adhesion molecules on monocytes and EC. In earlier studies we noticed that the monocyte-specific mAb, designated mAb 63D3, in contrast to mAb against the beta 2-integrin molecules, inhibited the monocyte binding to monolayers of rIL-1 alpha-stimulated venous EC. The aim of the present study was to further characterize the Ag recognized by mAb 63D3 and to investigate the specific contribution of this Ag to the adherence of monocytes to cultured human macrovascular venous or arterial EC. Flow cytometric analysis demonstrated that the 63D3 Ag is expressed exclusively on the surface of peripheral blood monocytes. SDS-PAGE analysis of mAb 63D3 immunoprecipitates of 125I-labeled human monocyte surface proteins revealed that the target Ag for mAb 63D3 is a 52- to 55-kDa molecule identical to the myeloid differentiation protein CD14. Stimulation of EC with rIL-1 alpha or rTNF-alpha for 4 or 24 h or rIFN-gamma for 24 h increased (p less than 0.005) the number of monocytes bound to both types of EC. This cytokine-induced increase in monocyte adherence was significantly (p less than 0.0005) inhibited when the monocytes were coated with various mAb against CD14. The binding of monocytes to nonstimulated venous or arterial EC was not inhibited by anti-CD14 mAb. Our results lead to the conclusion that CD14 molecules, which on basis of their structure and m.w. are not related to the beta 2-integrin family of heterodimeric leukocyte adhesion molecules, participate in the binding of monocytes to cytokine-stimulated EC.

Antibodies, Monoclonal↗
PubMed1991

A new competition binding assay for determination of the cAMP content of human leukocytes.

We developed a competition binding assay for measurement of the cAMP content of human cells based on specific binding sites for this messenger in a crude bovine adrenocortical preparation. The mean cAMP content of human granulocytes and lymphocytes was 1.13 +/- 0.32 microM and 1.81 +/- 0.23 microM, respectively. Stimulation of granulocytes with formyl-methionyl-leucyl-phenylalanine (f-MLP) induced a 2-3 fold increase in cAMP between 10 and 45 sec, which returned to resting values after 1 min. Lymphocytes did not react to f-MLP with a transient rise in intracellular cAMP content. This competition binding assay for cAMP is in essence similar to that for Ins(1,4,5)P3 (7), but conditions for the simultaneous assessment of both messengers could not be found. The present assay is rapid, easy to perform, sensitive and considerably cheaper than commercial kits for assessment of the cAMP content of cells.

Adrenal Cortex↗
PubMed1991

No effect of recombinant human interleukin-1 on numbers of peripheral blood and peritoneal leukocytes during acute inflammation.

Recombinant human interleukin-1 (IL-1) can prolong the survival of mice with severe systemic bacterial or fungal infections. In order to assess whether this is due to an effect of IL-1 on the production of leukocytes or their migration to the site of infection, the influence of IL-1 on the influx of leukocytes to the site of an acute inflammation was studied in normal and in granulocytopenic mice. The numbers of granulocytes, lymphocytes, and monocytes or macrophages in both the circulation and the peritoneal cavity were determined during an acute sterile inflammation elicited by intraperitoneal injection of either newborn calf serum (NBCS) or heat-killed Candida albicans, and during a peritoneal infection with viable C. albicans. After normal mice were injected intraperitoneally with NBCS or 10(7) CFU heat-killed or viable C. albicans, the number of peritoneal granulocytes rose sharply within 6 h. Pretreatment of mice with a single intraperitoneal dose of 80 ng IL-1 24 h before injection of an inflammatory stimulus did not influence the course of the numbers of leukocytes in the circulation or in the peritoneal cavity. When mice were rendered granulocytopenic by cyclophosphamide, both the influx of granulocytes into the peritoneal cavity and the concomitant rise in the number of peripheral blood granulocytes after injection of NBCS, killed or viable C. albicans was virtually absent. Pretreatment of granulocytopenic mice with IL-1 did not influence the course of the numbers of leukocytes in either the circulation or the peritoneal cavity. These findings show that the beneficial effect of a single dose of IL-1 on the course of candidal infections in normal or granulocytopenic mice is not attributable to the influx of granulocytes or monocytes.

Acute Disease↗
PubMed1991

Pneumococcal polysaccharide vaccines: indications, efficacy and recommendations.

Streptococcus pneumoniae is the primary cause of community-acquired pneumonia, meningitis in adults and otitis media in infants and children and the third cause of meningitis in infants and children. Despite the availability of effective therapeutic agents against this pathogen, mortality has remained high, particularly for infections complicated by bacteremia. For many years, there has been a plea for vaccination. The first steps, using whole bacterial vaccines, were taken during the early decades of this century in the gold mining camps of South Africa, where pneumonia was endemic. The efficacy of purified pneumococcal polysaccharide vaccines has since been demonstrated in young adults, such as gold miners and military recruits, as well as for several other groups at risk, such as institutionalized elderly, patients with sickle cell anemia or those who have undergone a splenectomy, and elderly patients with underlying conditions such as chronic obstructive pulmonary disease and chronic cardiovascular disease, but not in infants and severely immunocompromised patients. Serological studies on the immune response to inoculation of pneumococcal polysaccharide antigens have demonstrated a severely impaired antibody response in the last two groups. Therefore, development of more highly immunogenic vaccines, e.g. by linking pneumococcal polysaccharides or parts of them to protein carriers, should be continued in an attempt to offer adequate protection to those who are insufficiently protected by the current 23-valent polysaccharide vaccine. Opportunities to immunize other patients who are at risk for pneumococcal infection and are capable of responding to the current vaccine should not be missed.

Antibodies, Bacterial↗
PubMed1991

Binding of 99mTc-labelled polyclonal human immunoglobulin to bacteria as a mechanism for scintigraphic detection of infection.

The aim of the present study was to determine whether 99mTc-labelled polyclonal human immunoglobulin (99mTc-HIG) binds to bacteria in vitro as well as in vivo. In vitro, the binding of 99mTc-HIG to various gram-positive and gram-negative bacteria was determined. In vivo, mice were infected with Staphylococcus aureus Cowan I (protein A rich) or S. aureus EMS (protein A deficient) in a thigh muscle and then 99mTc-HIG or 99mTc-labelled human serum albumin (99mTc-HSA) was administered; scintigrams were made 1, 4, and 18 h later. In vitro binding of 99mTc-HIG to bacteria was higher for gram-positive than for gram-negative forms. A positive correlation was found between the protein A content and the degree of binding to S. aureus. This was also found in vivo. The accumulation of 99mTc-HIG at the site of infection was significantly (P less than 0.01) higher than that of 99mTc-HSA, for both strains of S. aureus. It is concluded that vascular permeability cannot fully explain the accumulation of 99mTc-HIG at the site of infection and that binding of 99mTc-HIG to bacteria plays a role in this respect.

Animals↗
PubMed1991

Nitrite production by activated murine macrophages correlates with their toxoplasmastatic activity, Ia antigen expression, and production of H2O2.

Activated macrophages have various characteristics in common with exudate and resident macrophages, but the ability to inhibit intracellular proliferation of the protozoa Toxoplasma gondii, the expression of Ia antigen and the capacity to produce H2O2 varies among these cells. Assessment of these features of macrophages, which are generally used as criteria for macrophage activation, has certain drawbacks. Since activated murine macrophages, but not exudate or resident macrophages, produce considerable amounts of NO2-, assessment of NO2- production by these cells might serve as a measure of macrophage activation. The aim of the present study was to find out whether NO2- production by murine peritoneal macrophages correlates with the three generally accepted criteria for macrophage activation. Quantitative data on resident, exudate and activated macrophages revealed that the production of NO2- stimulated by a calcium-ionophore correlates best with the ability to inhibit the proliferation of T. gondii, Ia antigen expression, and capacity to produce H2O2. Because it is rapid and easy to perform, measurement of the amount of NO2- produced by murine macrophages stimulated with a calcium-ionophore offers the most practical criterion for distinction between activated macrophages and exudate and resident macrophages.

Animals↗
PubMed1991

Comparison of the effects of aztreonam and tigemonam against Escherichia coli and Klebsiella pneumoniae in vitro and in vivo.

A study was performed to investigate the pharmacodynamics of aztreonam and tigemonam against Escherichia coli and Klebsiella pneumoniae in vitro and in vivo. The in vitro concentration-effect relationships were determined in short-term growth experiments. The in vivo dose-effect relationships were determined in an experimental thigh muscle infection in irradiated mice. In this model, E. coli was injected into one thigh muscle and K. pneumoniae was injected into the other. Throughout these experiments aztreonam was administered subcutaneously and tigemonam was administered orally. For analysis of the antibacterial pharmacodynamics, the following parameters were determined: the maximum effect as a parameter for efficacy, the 50% effective concentration (or dose) as a parameter for potency, and the slope of the concentration-effect relationship. To assess the relationship between the concentration of the antibiotic and the antibacterial effect in vivo, the pharmacokinetics of the two drugs in the plasma of mice were determined as well. The maximum in vitro and in vivo effects of aztreonam and tigemonam against both bacteria did not differ substantially. However, both drugs killed E. coli more effectively than K. pneumoniae, indicating that the maximum in vitro effect of these drugs against E. coli was higher than that against K. pneumoniae. The maximum in vivo effect of both drugs against E. coli was similar to that against K. pneumoniae. Furthermore, in vitro aztreonam was about twice as potent as tigemonam, but in vivo the reverse was the case. These findings were explained by pharmacokinetic differences between subcutaneously administered aztreonam and orally administered tigemonam, because concentrations of tigemonam in plasma remained at microbiologically active concentrations longer than those of aztreonam did.

Animals↗
PubMed1991

Modulation of the intestinal flora of mice by parenteral treatment with broad-spectrum cephalosporins.

A study was performed to determine the effect of parenteral treatment with four broad-spectrum cephalosporins (cefoperazone, ceftriaxone, ceftazidime, and cefepime) on the number of aerobic gram-negative rods and on the outgrowth of Candida albicans and a multiresistant strain of Citrobacter freundii in the feces of mice. The estimated fractions of a parenteral dose that were excreted into the gastrointestinal tract were 0.37 for cefoperazone, 0.11 for ceftriaxone, 0.03 for ceftazidime, and 0.002 for cefepime. All four cephalosporins significantly decreased the number of aerobic gram-negative rods in the feces, and virtually all gram-negative rods were eliminated at high doses of cefoperazone, ceftazidime, and ceftriaxone. Furthermore, at high doses these three compounds led to a significant increase of the outgrowth of resistant Citrobacter freundii. The outgrowth of Candida albicans was increased at high doses of cefoperazone and ceftriaxone, whereas ceftazidime and cefepime did not have this effect. The most profound changes in the gastrointestinal ecology were observed during treatment with high doses of cefoperazone. The results suggest that the colonization resistance of the gastrointestinal tract can be substantially decreased by parenteral treatment with cefoperazone and, to a lesser extent, with ceftriaxone and ceftazidime.

Animals↗
PubMed1991

Modulation of the intestinal flora of mice by treatment with aztreonam and tigemonam.

Oral and parenteral administration of aztreonam and oral administration of tigemonam to conventional mice caused a decrease in the number of aerobic gram-negative rods in the feces. Oral treatment with high doses of aztreonam (greater than or equal to 25 mg/kg/day) and tigemonam (100 mg/kg/day) adversely influenced colonization resistance, whereas oral treatment with lower doses of the monobactams or parenteral treatment with aztreonam did not.

Administration, Oral↗
PubMed1991

Microbicidal activities of Salmonella typhimurium- and interferon-gamma-activated mouse peritoneal macrophages.

Activation of mouse peritoneal macrophages during infection of mice by various facultative intracellular bacteria and after intravenous injection of recombinant interferon-gamma (rIFN-gamma) was studied. Macrophage activation was demonstrated on the basis of three different criteria, i.e. inhibition of Toxoplasma gondii proliferation, enhanced release of H2O2 and increased expression of Ia antigen. Macrophages activated during an infection with Salmonella typhimurium showed no enhanced salmonellacidal or listericidal activity relative to control macrophages, whereas Listeria-activated macrophages killed Listeria but not Salmonella faster than control macrophages. The rate of proliferation of Salmonella in spleen and liver of activated mice was comparable to the proliferation in the organs of control mice. rIFN-gamma-activated macrophages displayed neither an enhanced salmonellacidal nor an enhanced listericidal activity. When high numbers of Listeria were injected intravenously the proliferation in spleen and liver of rIFN-gamma-treated and control mice was similar. The proliferation of Listeria in the liver of rIFN-gamma-treated mice was less than in control mice when 1 LD50 or lower numbers of bacteria were injected. It is concluded that peritoneal macrophages become activated during infections of mice with various intracellular pathogens. However, these activated macrophages do not show enhanced bactericidal activity against all bacteria. Furthermore, rIFN-gamma is not sufficient to enhance the listericidal activity of macrophages.

Animals↗
PubMed1991

Evaluation of cloxacillin concentrations in plasma and muscle tissue during cardiopulmonary bypass.

Concentrations of cloxacillin in plasma and deep thoracic muscle tissue were measured in 10 patients who underwent elective coronary bypass surgery or valve replacement. One g of cloxacillin was administered after the induction of anaesthesia and 1 g cloxacillin was added to the oxygenator pump priming fluid before the start of the procedure. Blood and tissue samples were obtained before, during and after cardiopulmonary bypass. The relation between unbound plasma concentrations and total tissue contents of the drug was calculated. It was shown that measurement of the free plasma concentration may provide fairly reliable information on the free concentrations of cloxacillin in the tissues, and that determination of tissue contents may therefore not be necessary. Due to the administration of the second dose of cloxacillin at the start of cardiopulmonary bypass free tissue contents were just adequate in most patients. However, to obtain adequate tissue concentrations after bypass it is recommended that a third dose of the antibiotic be administered before the end of the operation.

Adult↗
PubMed1991

Effect of monomeric immunoglobulin G (IgG) on the clearance of soluble aggregates of IgG in man.

Serum concentrations of IgG may influence Fc receptor-mediated clearance of immune complexes. For instance, when 123I-labeled aggregates of human IgG (123I-AIgG), used as a model for soluble immune complexes, are administered to patients with systemic lupus erythematosus (SLE), there is an inverse correlation between the serum concentrations of IgG and the clearance and volume of distribution in steady state (Vss) of 123I-AIgG. To answer the question whether IgG has a direct effect on the clearance of immune complexes, we measured the elimination of 123I-AIgG in eight patients with hypogammaglobulinemia, before and after substitution with intravenous gammaglobulin (IVIG). As expected, raising IgG concentrations in these patients (by 6 g/l) caused a significant decrease of the Vss of 123I-AIgG. However, clearance of 123I-AIgG remained unchanged by IVIG. Thus, the results of this study offer no experimental evidence that raising concentrations of IgG influences the clearance of soluble immune complexes.

Adult↗
PubMed1991

Effect of probenecid on phagocytosis and intracellular killing of Staphylococcus aureus and Escherichia coli by human monocytes and granulocytes.

The present study concerns the effects of probenecid on the phagocytosis and intracellular killing of Staphylococcus aureus and Escherichia coli by human monocytes and granulocytes. In both monocytes and granulocytes the inhibitory effect on phagocytosis was very small. Inhibition of intracellular killing of S. aureus by monocytes and granulocytes by probenecid was concentration dependent, being half-maximal at about 2 mM probenecid, and near-maximal at about 5 mM probenecid. The intracellular killing could also be inhibited when probenecid was added when this process was already started. Probenecid also inhibited the intracellular killing of E. coli by granulocytes, but not by monocytes. In the concentration range used, probenecid had no toxic effect on phagocytes or bacteria during the 2 hr of the experiments.

Dose-Response Relationship, Drug↗
PubMed1991

Detection of a local staphylococcal infection in mice with technetium-99m-labeled polyclonal human immunoglobulin.

The purpose of this study was to investigate both the ability of 99mTc-labeled polyclonal human immunoglobulin (HIG) to localize an infection and the modes of action involved in this process. Mice, infected with Staphylococcus aureus ATCC 25923 in a thigh muscle, received HIG intravenously. Scintigrams were made 1, 4, and 24 hr later; subsequently the mice were killed and the activity in several organs and thighs was determined. The radiopharmaceutical demonstrated a time-dependent accumulation at the site of infection. It was found that vascular permeability or Fc binding alone could not account for the mode of action of HIG. Neither the origin of Ig (human versus murine) nor the total amount of protein (0.01-1.0 mg Ig per mouse) affected the target-to-background (T/B) ratios. Ratios were not different for leukocytopenic animals. A correlation (p less than 0.001) was demonstrated between the number of bacteria at the site of infection and the T/B ratio. This was also found after antibiotic treatment (p less than 0.02).

Animals↗
PubMed1990

A competition binding assay for determination of the inositol (1,4,5)-trisphosphate content of human leucocytes.

We developed a competition binding assay for estimation of the intracellular inositol (1,4,5)-trisphosphate (Ins(1,4,5)P3) and optimalized it for the measurement of the Ins(1,4,5)P3 content of human blood leucocytes. The present method is considerably cheaper and requires five times fewer cells than the commercial Ins(1,4,5)P3 kit. The mean Ins(1,4,5)P3 content of human blood monocytes, granulocytes, and lymphocytes amounted to 3.3 +/- 1.2 microM, 3.1 +/- 1.4 microM, and 4.6 +/- 1.5 microM, respectively. After stimulation with formyl-methionyl-leucyl-phenylalanine (f-MLP) the Ins(1,4,5)P3 content of human granulocytes and monocytes increased 2-3 times within 10 sec and then gradually decreased, returning to basal values at 60 sec. Lymphocytes did not respond to f-MLP with an increase in their Ins(1,4,5)P3 content.

Binding, Competitive↗