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Biomedical subjects

R van Furth

Publications and source records attributed to R van Furth.

At least 145 records · Page 8Linked to original sources
PubMed1990

Characterization of monocyte adherence to human macrovascular and microvascular endothelial cells.

The interaction of monocytes with cultured large vessel venous and arterial endothelial cells (EC) and with cultured microvascular EC was studied. Analysis of time-lapse microcinematographic video recordings showed that monocytes adhere rapidly to the surface of EC and subsequently remain spherical and fixed to the initial site of adherence. Some monocytes adherent to EC stretch out within 30 to 90 min and migrate over the EC surface or become stretched for about 10 to 30 min and then detach from the EC surface and move rapidly over the EC monolayer. It was shown that the interaction of monocytes with EC is dynamic, that the morphology of monocytes adherent to EC changes constantly, and that stretching of the monocytes over the surface of the EC is not an inevitable and irreversible consequence of binding. A quantitative adherence assay was developed in which both the morphology and the number of monocytes bound to EC were determined. For each type of EC the number of monocytes bound to a single EC was found to be linearly related to the number of monocytes added and was lower for smaller EC. The adherence of monocytes to venous and arterial EC followed a different time course than the adherence to capillary EC and adherence to both types of macrovascular EC was higher than adherence to microvascular EC was higher than adherence to microvascular EC. The percentage of adherent monocytes with a stretched morphology was lower when these cells were adherent to capillary EC than to both types of macrovascular EC and increased upon addition of serum. Adherence of monocytes to venous, arterial, and capillary EC was partially inhibited by mAb directed against the alpha-chain of lymphocyte function-associated Ag-1 or C3bi receptor (with mAb LM2/1, but not with mAb OKM1) and by mAb against the common beta-chain of the three leukocyte adhesion molecules. The degree of inhibition of monocyte adherence to EC by mAb against lymphocyte function-associated Ag-1 alpha and the common beta-chain was dependent on the type of EC and was higher for venous EC (57 to 70% inhibition) than for arterial (40 to 44% inhibition) and capillary (44 to 49% inhibition) EC. Inhibition of monocyte adherence obtained with anti-C3bi receptor-alpha mAb was similar for each EC type. mAb against p150, 95 did not affect adherence. None of the mAb could block binding completely; combinations of the mAb also did not result in increased inhibition of monocyte adherence to EC.

Antibodies, Monoclonal↗
PubMed1990

Activation of mouse peritoneal macrophages during infection with Salmonella typhimurium does not result in enhanced intracellular killing.

Our study was performed to investigate whether macrophages become activated during an infection with Salmonella typhimurium and, if so, whether these activated macrophages kill S. typhimurium faster than resident macrophages. Mice received i.v. injections with a sublethal number of S. typhimurium; on about day 12 of the infection the numbers of bacteria in the liver and the spleen were maximal. During the infection, activation of peritoneal macrophages could be demonstrated on the basis of three criteria, i.e., the ability to inhibit the proliferation of Toxoplasma gondii, an enhanced production of H2O2 and an increased expression of Ia Ag. The rate of in vitro intracellular killing of S. typhimurium by these activated macrophages was not increased compared to that for resident macrophages. To determine the growth of S. typhimurium in activated mice a nalidixic acid-resistant mutant strain, called S. typhimurium 510R, was used. The net growth rates of the mutant S. typhimurium 510R in the spleen of S. typhimurium 510-activated and normal mice were similar. However, in the liver of S. typhimurium 510-activated mice the number of S. typhimurium 510R did not change during 3 to 48 h after injection. The role of specific antibodies during the initial phase of the infection was negligible, because only low levels of antibodies were detected during the first 15 days of infection and the growth rates of S. typhimurium 510 in the spleen and liver of mice with high titers of antibodies were not significantly different from the rates in normal mice. The results of this study demonstrate that although macrophages become activated during an infection with S. typhimurium, these cells do not display an enhanced bactericidal activity in vitro and in vivo no significant effect on the growth rate of S. typhimurium in the spleen and a bacteriostatic effect in the liver is found. Hence macrophage activation is probably not very important in the host defense against S. typhimurium.

Animals↗
PubMed1990

Mycobacteria and macrophage activation.

Recent studies that challenged some older concepts have led to the following conclusions: 1) During an infection of mice with M. bovis, BCG macrophages are activated according to certain criteria, but the increase in their bactericidal or bacteriostatic activity is limited to a small number of bacteria species; 2) interferon-gamma can activate macrophages in vitro and in vivo, but these cells do not exhibit increased bactericidal activity; 3) a 65-kDa protein of mycobacteria can activate macrophages in vivo to a limited degree only; and 4) granulocytes stimulated with interferon-gamma kill ingested M. fortuitum more efficiently than normal granulocytes.

Animals↗
PubMed1990

Decreased natural killer cell activity in late-onset hypogammaglobulinaemia.

1. Natural killer cell activity and monocyte cytotoxicity was evaluated in three subgroups of patients with primary hypogammaglobulinaemia (ten patients with late-onset, eight with X-linked and five with early-onset disease) and in two patients with secondary late-onset hypogammaglobulinaemia against the K-562 erythroleukaemia, the CaCo-2 colon carcinoma and the HGT-1 gastric carcinoma cell lines and compared with the results found in healthy control subjects. 2. The natural killer cell activity, both spontaneous and after stimulation with recombinant gamma-interferon, was found to be decreased in patients with late-onset hypogammaglobulinaemia. The natural killer cell activity in this subgroup was found to be impaired in 60% of the patients (P less than 0.05). Within the other forms of primary hypogammaglobulinaemia a decreased natural killer cell activity was found to be less frequent (33%). 3. The lectin-mediated cytotoxicity by phytohaemagglutinin resulted in a similar maximal cytotoxicity in patients and control subjects. 4. The cytotoxicity of monocytes, spontaneous and after recombinant gamma-interferon stimulation, was found to be normal in all patients with hypogammaglobulinaemia. 5. The impaired natural killer cell activity which was found in patients with late-onset hypogammaglobulinaemia may contribute to the increased susceptibility to infections and to the increased incidence of malignancies in this subgroup of patients with primary hypogammaglobulinaemia.

Adolescent↗
PubMed1990

Pneumococcal anticapsular antibodies in patients with chronic cardiovascular and obstructive lung disease in The Netherlands.

Differences in pneumococcal anticapsular antibody concentrations were assessed among patients with various chronic disorders and among young (25-35 years of age) and older adults (55-65 years). Antibody concentrations were determined by ELISA, using the whole 23-valent pneumococcal polysaccharide vaccine as antigen. No differences in mean or distribution of serum antibody concentrations were found among young adults (either healthy or asthmatic) or among older adults (healthy or with chronic obstructive pulmonary or chronic cardiovascular disease). Each group included individuals with low antibody levels. Therefore, the enhanced susceptibility to pneumococcal infections reported for some groups at risk, that is, elderly individuals and patients with chronic obstructive pulmonary or chronic cardiovascular disease, cannot be attributed solely to low anticapsular antibody concentrations.

Adult↗
PubMed1990

Relation between the therapeutic efficacy of imipenem in an experimental infection in granulocytopenic mice and its effect on murine intestinal microbial ecology.

A study was performed to assess the effect of parenteral administration of imipenem on the intestinal microbial ecology of mice in relation to the therapeutic efficacy of the drug. The therapeutic effect of imipenem was assessed in a short-term experimental thigh muscle infection with Escherichia coli in irradiated mice. The maximum antibacterial effect of imipenem was approached at a single dose of 80 mg/kg. At this dose of imipenem the number of viable E. coli in the thigh muscle decreased from 9 x 10(6) to 4 x 10(5), whereas in untreated controls this number increased from 9 x 10(6) to 2 x 10(8). Daily administration of a dose of 80 mg/kg imipenem caused significant changes in the intestinal flora of conventional mice, despite the low concentrations of the drug (about 1 mg/kg) found in the caecum 30 min after infection of this dose. These changes consisted of an increase in the number of E. coli and enterococci and a decrease in the number of Staphylococcus aureus in the faeces. Furthermore, at this dose of imipenem, the number of Candida albicans recovered from the faeces after oral contamination with this organism was increased. We conclude from these animal experiments that the use of imipenem in high doses causes ecological changes in the intestinal bacterial flora with the potential to promote colonization by candida.

Animals↗
PubMed1990

Comparative study of the effects of four cephalosporins against Escherichia coli in vitro and in vivo.

A thigh muscle infection induced with Escherichia coli in irradiated mice was used as a model to compare the in vivo pharmacodynamics of the antibacterial effect of four cephalosporins (i.e., cefepime, ceftriaxone, ceftazidime, and cefoperazone) with the in vitro antibacterial pharmacodynamics of these drugs. The following in vitro pharmacodynamic parameters were determined: the maximum effect as a measure for efficacy, the 50% effective concentration as a parameter for potency, and the slope of the concentration-effect relationship. For analysis of the in vivo antibacterial pharmacodynamics, the same parameters were applied for the dose instead of the concentration. For the detection of a relationship between concentration and antibacterial effect in vivo, we determined the pharmacokinetics of the four cephalosporins in the plasma of mice. The results showed that, in general, there is a direct relationship between the in vivo and in vitro pharmacodynamics of these cephalosporins. The maximum effects of cefepime, ceftazidime, and cefoperazone were approximately similar in vivo and in vitro. The sequence of potency of these drugs was, in descending order, cefepime, ceftazidime, and cefoperazone. Ceftriaxone differed from the other three cephalosporins in that it displayed unexpected in vivo pharmacodynamics. Ceftriaxone was just as efficacious as the other three in vitro, but its maximum effect in vivo was much lower. This relatively low maximum effect of ceftriaxone in vivo was not explained by the pharmacokinetic characteristics of the drug. From the present results it can be concluded that the in vitro efficacy of cephalosporins does not necessarily have a predictive value for the in vivo efficacy.

Animals↗
PubMed1990

Role of granulocytes in increased host resistance to Candida albicans induced by recombinant interleukin-1.

The effect of human recombinant interleukin-1 alpha (IL-1 alpha) on a systemic candidal infection in mice under various conditions of immunosuppression was investigated. In normal mice and in mice pretreated with cyclophosphamide, hydrocortisone acetate, or sublethal total body irradiation, the outgrowth of Candida albicans in the kidney was significantly reduced by the administration of a single intraperitoneal dose of 80 ng of IL-1 (P less than 0.05). In mice treated with either cyclophosphamide or irradiation, IL-1 also significantly reduced the outgrowth of C. albicans in the spleen. The protective effect of IL-1 was present when given 24 h before injection of C. albicans but also when IL-1 was given simultaneously with or 6 h after injection of C. albicans in cyclophosphamide-treated mice. The effect of IL-1 was independent of the presence or recruitment of granulocytes, since IL-1 inhibited the outgrowth of C. albicans in the kidneys and spleens of mice that were rendered severely granulocytopenic (less than 50 granulocytes per mm3) throughout the duration of the infection by either repeated injections of cyclophosphamide or sublethal total body irradiation. These results indicate that the enhancement of host resistance by IL-1 is not due solely to increased granulocytopoiesis or chemotaxis of granulocytes but strongly suggest that other mechanisms play a role in the protective effect of IL-1 against systemic infections.

Analysis of Variance↗
PubMed1990

Effect of cloxacillin prophylaxis on the bacterial flora of craniotomy wounds.

During a double-blind placebo-controlled study, the effect of cloxacillin prophylaxis in craniotomies on samples taken for culture from 334 operation wounds in 279 patients was assessed. Patients and operations were equally divided over the cloxacillin and placebo groups. In the cloxacillin group significantly fewer samples contained microorganisms than was the case in the placebo group both just after the incision was made (p less than 0.05) and just before closure of the wound (p less than 0.001). The contaminating bacteria found most frequently were Propionibacterium acnes and Staphylococcus epidermidis. For material collected immediately after the incision, the percentage of cultures positive for S. epidermidis was significantly (p = 0.001) lower in the cloxacillin group than in the placebo group; the percentage of cultures with P. acnes did not differ between the two groups. For samples taken just before the wound was closed, the percentage of cultures with P. acnes or S. epidermidis was significantly (p = 0.008 and 0.003, respectively) lower in the cloxacillin than in the placebo group. In the placebo group neurosurgical infections occurred with P. acnes and/or S. epidermidis as causative microorganisms; in almost all cases those bacteria could be cultured from the edge of the wound. In none of the patients with an infection caused by S. aureus was the bacteria found in the operation area. In 2/6 infections in the cloxacillin group the infecting microorganisms could be cultured from the operation area. These findings support a significant reduction in the infection rate after craniotomy under cloxacillin prophylaxis compared with placebo.

Cloxacillin↗
PubMed1989

[Pulmonary and extra-pulmonary forms of tuberculosis; clinical experiences in the 80s].

In the period 1980-1984, 85 patients with tuberculosis were seen at Leyden University Hospital. In this retrospective study clinical data of 76 patients with pulmonary, extrapulmonary, miliary and disseminated tuberculosis are presented. 43 patients suffered from pulmonary tuberculosis. Three patients suffered from miliary tuberculosis and three patients from disseminated tuberculosis. Eight patients suffered from pleuritis tuberculosa, of whom three also suffered from pulmonary tuberculosis. The heterogeneity and often rather non-specific, sometimes surprising clinical aspects of tuberculosis are highlighted by a variety of clinical case histories.

Adolescent↗
PubMed1989

Macrophages in bronchoalveolar lavage fluid are not representative of macrophages in granulomas of the lungs of BCG-infected mice.

To find out whether macrophages obtained by bronchoalveolar lavage (BAL) represent the macrophage population in alveoli, we performed a quantitative study to compare the expression of cell-surface antigens by macrophages in the lavage fluid as well as in the alveolar spaces of sectioned lung tissue from normal and BCG-infected mice. The amount of antigen on cells, determined with a quantitative immunocytochemical method, was expressed as the mean specific absorbance per 0.25 micron2 cell-surface area. In normal mice, BAL and intra-alveolar macrophages are identical. Macrophages in BAL fluid and intra-alveolar macrophages, both from BCG-infected mice, expressed antigen F4/80 and Fc receptor II to about the same extent, but the former showed a significantly higher level of antigen expression as defined by antibodies M1/70, M5/114, 30.G.12, and M3/38. In granulomatous lesions, expression of antigens by macrophages, assessed semi-quantitatively, was considerably less than that by BAL macrophages. Lymphocytes in the BAL fluid resembled those in the granulomas. These findings led to the conclusion that in BCG-infected mice, the macrophages found in BAL fluid do not resemble those occurring in either the alveoli or the granulomatous lesions of the lungs. On these grounds, the relevance of findings in BAL fluid to lung interstitial lung diseases should be reconsidered.

Animals↗
PubMed1989

Effect of irradiation, cyclophosphamide, and etoposide (VP-16) on number of peripheral blood and peritoneal leukocytes in mice under normal conditions and during acute inflammatory reaction.

In order to develop a suitable model for studying the role of granulocytes and monocytes in resistance against pathogenic microorganisms, we investigated the effect of irradiation and cytostatic treatment (cyclophosphamide and VP-16) on the number of both peripheral blood and peritoneal leukocytes in male Swiss mice. Irradiation and cyclophosphamide treatment severely decreased the number of both granulocytes and monocytes in peripheral blood, whereas VP-16 only lowered the number of blood monocytes to a significant degree and had little effect on the number of blood granulocytes or lymphocytes. When normal mice were injected intraperitoneally with newborn calf serum (NBCS) the number of peritoneal granulocytes rose about 100-fold within 6 h. In irradiated and cyclophosphamide-treated mice, this influx of granulocytes into the peritoneal cavity was virtually eliminated, as was the concomitant increase in the number of blood granulocytes; in VP-16-treated mice, on the other hand, the number of peripheral blood and peritoneal granulocytes increased to the same degree as in normal mice. An increase in the number of peripheral blood monocytes and peritoneal macrophages occurred 24-48 h after injection of NBCS in normal mice. This increase was significantly impaired by irradiation as well as by treatment with cyclophosphamide or VP-16.

Animals↗