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Biomedical subjects

R van Furth

Publications and source records attributed to R van Furth.

At least 217 records · Page 12Linked to original sources
PubMed1986

Comparison of the effect of phenoxymethylpenicillin, cloxacillin, and flucloxacillin on Staphylococcus aureus phagocytosed by human monocytes.

The antibacterial effect of phenoxymethylpenicillin, cloxacillin, and flucloxacillin on pre-opsonized Staphylococcus aureus ingested by human monocytes and on preopsonized S. aureus in suspension was compared. The antibiotics were 1.7-3 times more effective against intracellular S. aureus than against S. aureus in suspension. No influence of acid stability or lipid solubility of the drugs on the antibacterial effect against intracellular S. aureus was demonstrated.

Cloxacillin↗
PubMed1986

Genetic control of macrophage responses.

A short review of current concepts concerning the origin and kinetics of monocytes and macrophages is given, and the humoral regulation of monocyte production by FIM, a factor synthesized and secreted by macrophages, is discussed. Genetic control of the responsiveness of monocyte precursors to FIM and that of the phagocytosis and intracellular killing of bacteria is dealt with.

Animals↗
PubMed1986

Influence of human monocytes on the antibacterial activity of kanamycin and gentamicin for Staphylococcus aureus.

The present study was performed to compare the antibacterial activities of kanamycin and gentamicin on Staphylococcus aureus phagocytosed by human monocytes and on nonphagocytosed S. aureus. The method used permitted the measurement of the effect of antibiotics on intracellular bacteria independent of phagocytosis and intracellular killing by the monocytes. A morphological assay with lysostaphin established the intracellular localization of about 70% of the cell-associated S. aureus in the monocyte-bacterium suspension. After 1 h of incubation, the antibacterial activity of both aminoglycosides was greater against intracellular than against nonphagocytosed S. aureus, but after 3 h, the reverse was true. The maximal effect on phagocytosed S. aureus, i.e., killing of about 98% of the bacteria, was reached in the first hour of incubation at kanamycin and gentamicin concentrations of 5 and 1 microgram/ml, respectively. A cell-free medium in which monocytes had been incubated increased the antibacterial activity of kanamycin, indicating that monocytes secrete a factor that enhances the antibacterial activity of aminoglycosides.

Anti-Bacterial Agents↗
PubMed1986

Selective antimicrobial modulation of the intestinal microbial flora for infection prevention in patients with hematologic malignancies. Evaluation of clinical efficacy and the value of surveillance cultures.

To confirm the results obtained in an earlier study, the incidence of infection was evaluated in 54 patients (62 periods of admission), nursed in conventional rooms and given a regimen of antimicrobial agents intended to modulate the intestinal flora selectively as a method to prevent infection during severe granulocytopenia. In 62 patients receiving selective antimicrobial modulation (SAM), 18% acquired major infections which was similar to 19% in patients on SAM in an earlier double-blind placebo controlled study and lower than 47% in the controls. Evaluation of a large number of surveillance cultures showed that the presence of specific potentially pathogenic aerobic bacteria was associated with the occurrence of major infection. If the bacterial species in question were not found in the cultures the chance of becoming infected was less than 5%, whereas the chance ranged between 42 and 62% depending on the species involved when these microorganisms were isolated.

Acute Disease↗
PubMed1986

Change in alpha 1-antitrypsin phenotype after orthotopic liver transplant.

The aim of the present study was to determine the interval after orthotopic liver transplant during which the alpha 1-AT phenotype in the serum changes. Eleven patients could be evaluated because the donor and recipient had different alpha 1-AT phenotypes. The results showed that within 1 to 3 days of the transplant donor alpha 1-AT is already present in the serum of the recipient, and subsequently the transplanted liver continued to synthesize alpha 1-AT of the donor phenotype. The result confirmed that liver parenchymal cells are the main site of alpha 1-AT synthesis.

Humans↗
PubMed1985

Phagocytosis and intracellular killing by polymorphonuclear cells from patients with rheumatoid arthritis and Felty's syndrome.

The present in vitro study concerned the phagocytosis and intracellular killing by polymorphonuclear cells (PMN) of 5 patients with rheumatoid arthritis (RA) and 12 patients with Felty's syndrome (FS). PMN phagocytosis was assessed by microbiologic and morphologic methods, and intracellular killing was measured independently of continuous phagocytosis of viable bacteria (Staphylococcus aureus). PMN from patients with RA or FS ingested S aureus opsonized with immunoglobulins and complement as effectively as did PMN from healthy donors. However, the capacity of patient PMN to ingest S aureus opsonized with sera lacking complement activity, e.g., heat-inactivated donor serum and the sera of 2 patients with FS, was lower than that of healthy donor PMN. This decreased ingestion is associated with diminished expression of Fc receptors on the membrane of PMN from patients who have RA or FS. As with sera lacking complement activity, decreased capacity to ingest S aureus was observed after preloading donor PMN with immune aggregates, which also decreased the expression of Fc receptors. PMN from patients with RA or FS were found to be as active in killing S aureus as cells from healthy donors.

Adult↗
PubMed1985

Morphological, cytochemical, functional, and proliferative characteristics of four murine macrophage-like cell lines.

The aim of the present study was to obtain objective data on the morphology and quantitative information about other characteristics of murine macrophage-like cell lines J774.1, PU5-1.8, WEHI-3, and P388-D1, and to compare the findings with those in resident and exudate macrophages collected directly from mice. Fetal fibroblasts were included to serve as controls. Evaluation of the morphological data showed that the cell lines J774.1 and WEHI-3 are almost identical in most respects, that the cells of P388-D1 differ widely from both of the former lines, and that the morphometric parameters of cell line PU5-1.8 occupy an intermediate position. The cells of the P388-D1 line show the most similarity to resident and exudate macrophages, and cell lines J774.1 and WEHI-3 the least. Fetal fibroblasts had divergent values for all morphometric parameters. Good correspondence was found when the quantitative data obtained by morphometric analysis of the cells in question were compared with the morphological pictures. No gross differences as to cytochemical characteristics were found between the cells of the four cell lines, except for 5'-nucleotidase activity. The occurrence of IgG receptors and the ingestion of EIgG were also similar, but the percentage of cells with C3b receptors was much lower in two of the cell lines (WEHI-3 and P388-D1) and the level of EIgMC ingestion was very much higher in one (J774.1) compared with both the other cell lines and the resident and exudate macrophages. The ingestion of opsonized bacteria and latex varied widely within and between the cell lines. Quantitative data on the binding of monoclonal antibodies by the cells of the macrophage cell lines and the resident and exudate macrophages showed a wide variation. The doubling time of the cell lines is on average 1 day; distinct differences were found between these lines with respect to the lag-time of proliferation after replating. Cluster analysis and statistical analysis of morphological and other characteristics gave insight into the degree of resemblance between the cells of the four cell lines on the one hand and the resident and exudate macrophages on the other.

Animals↗
PubMed1985

Monocyte production during inflammation.

The majority of the resident macrophages in non-inflamed organs and serous cavities derive from circulating monocytes, but a small proportion originate from immature mononuclear phagocytes that only divide once in the tissues and originate from the bone marrow as well. During an acute inflammation the number of circulating monocytes increases, and a large proportion of these cells migrate to the site of inflammation and differentiate into exudate macrophages. The monocyte production during an acute inflammation is controlled by humoral factor, FIM, which is a protein that is synthesized and secreted by macrophages at the site of inflammation.

Animals↗
PubMed1985

Role of granulocytes and monocytes in the prevention and therapy of experimental Staphylococcus epidermidis endocarditis in rabbits.

Rabbits with endocarditis caused by Staphylococcus epidermidis were studied to determine the parts played by granulocytes and monocytes in the prevention or outcome of therapy with cloxacillin. Both monocytes and granulocytes influenced prophylaxis with cloxacillin. The amount of cloxacillin needed to prevent infection in 50% of the rabbits was significantly less in control rabbits than in those selectively depleted of monocytes, as it was also in rabbits selectively depleted of monocytes compared with those that had both granulocytopenia and monocytopenia. Granulocytes strongly potentiated the effect of cloxacillin during prophylaxis, whereas the contribution of monocytes was merely additive. Monocytes also contributed to the effect of therapy with cloxacillin, partially via a cloxacillin-independent mechanism and partially by potentiation of the effect of cloxacillin. Granulocytes did not appear to affect cloxacillin therapy. Results of this study suggest that currently used regimens for prophylaxis and treatment of S. epidermidis endocarditis may need to be adjusted for neutropenic patients.

Animals↗
PubMed1985

Water-related nosocomial pneumonia caused by Legionella pneumophila serogroups 1 and 10.

Between August 1978 and November 1983, 21 cases of pneumonia caused by Legionella pneumophila occurred in the Leiden University Hospital, mainly among immunocompromised patients. A new serogroup of L. pneumophila, designated serogroup 10 (prototype strain Leiden 1), was isolated from bronchial secretions of four patients, and five patients had serological evidence of infection with this organism. Nine patients had a culture-confirmed infection with L. pneumophila serogroup 1. L. pneumophila serogroups 1 and 10 were also isolated from the hot potable water supply in the building to which 19 of the 21 patients had been admitted. The isolates of L. pneumophila serogroup 1 from patients and the hot potable water were identical in studies with monoclonal antibodies and had the same plasmid profiles. These findings provide further evidence that in our hospital potable water contaminated with L. pneumophila is a source of infection, mainly in immunocompromised patients.

Adult↗
PubMed1985

Interaction between human monocytes and penicillin G in relation to the antibacterial effect on Staphylococcus aureus.

The influence of the presence of monocytes on the effect of penicillin G on Staphylococcus aureus was studied. Conditions were varied in such a way that phagocytosis and intracellular killing of S. aureus by monocytes did not occur, was short lasting and limited, or long lasting and extensive. Synergism between penicillin G and monocytes was observed in the absence of and during limited phagocytosis and intracellular killing by the monocytes. When phagocytosis and intracellular killing were optimal, addition or antagonism between penicillin G and monocytes was observed. Enhancement of the antibacterial effect of penicillin G was also obtained in the presence of monocyte supernatant (the cell-free medium in which monocytes had been incubated for 3 hr). This indicates that monocytes secrete a factor that enhances the antibacterial activity of penicillin G. Serum inhibits the activity of this factor.

Adult↗
PubMed1985

Comparison of the antibacterial activity of azlocillin and ticarcillin in vitro and in irradiated neutropenic mice.

The antibacterial efficacy of azlocillin against Pseudomonas aeruginosa was quantitatively assessed in short-term growth curves in vitro and in a short-term thigh muscle infection in granulocytopenic mice. Ticarcillin was used as the reference drug. The antibacterial effect in vitro was expressed as the difference between the logarithms of the numbers of cfu in the presence and absence of antibiotics (log ratio). The log ratio-time curves could be described by a concentration-dependent parameter, i.e., the inhibition constant (i). According to a standard parallel line bio-assay, based on values of i, azlocillin was 3.80 times more active than ticarcillin (coefficient of variation 27%). Tobramycin in a concentration of 0.19 mg/l, which is not effective in itself, potentiated both drugs by a factor of 3.85 (coefficient of variation 26%). In the in vivo model ticarcillin showed a dose-dependent antibacterial effect, whereas the effect of azlocillin was limited and not dose dependent. The effect of tobramycin in a dose of 4 mg/kg was additive for both penicillins. The results obtained in vivo were less favourable for azlocillin than would be predicted on the basis of the in-vitro results.

Animals↗
PubMed1985

The characterization, origin, and kinetics of skin macrophages during inflammation.

This report deals with the characterization, origin, and kinetics of exudate skin macrophages. The inflammatory stimulus used was a subcutaneously inserted glass coverslip. The macrophages adhering to the glass surface have many characteristics in common with circulating monocytes. During this kind of inflammation there is little differentiation into a more mature or activated type of mononuclear phagocyte. The kinetic studies with [3H]thymidine as cell marker and calculation of local production at the site of inflammation as well as the influx of cells to that site led to the conclusion that greater than or equal to 99% of the exudate skin macrophages were monocyte derived and less than or equal to 1% originated by local division of macrophages.

Animals↗
PubMed1985

Comparative pharmacodynamics and clinical pharmacokinetics of phenoxymethylpenicillin and pheneticillin.

In this study the antimicrobial effects of phenoxymethylpenicillin (PM) and pheneticillin (PE) in vitro and in an experimental animal infection model were compared as well as the pharmacokinetic properties of both drugs in patients. For the inhibitory effect of PM on short-term (3 h) growth of S. aureus in vitro, this drug was 2.13 times more potent than PE. The protein binding of both drugs was similar (78-80%). The potency ratio of PM to PE against S. aureus in an experimental mouse-thigh infection was only 1.25 to 1. This is explained by the difference in the AUC after subcutaneous administration of PM (0.47 mg 1(-1) h) and PE (0.92 mg 1(-1) h). The plasma clearance after intravenous administration of PM was 476.4 ml/min and that of PE was 295.1 ml/min; the plasma clearance of both drugs was strongly correlated with the creatinine clearance. The volume of distribution in the steady state of PM was 35.41 and that of PE 22.51. In 10 patients, the absorption after oral administration of PM as the acid was 48% and that of the potassium salt of PE was 86% of the dose. From the present results it can be concluded that a difference in effectiveness of different formulations of PM and PE would depend entirely on differences in absorption.

Adult↗
PubMed1985

Adherence of lysostaphin to and penetration into human monocytes.

The effect of lysostaphin on Staphylococcus aureus phagocytosed by monocytes was investigated. The results showed that lysostaphin adheres to monocytes by a temperature-independent mechanism, is not adequately removed from monocytes by washing, and penetrates by means of a temperature-dependent mechanism. In in vitro assays of monocyte function, phagocytosed S. aureus can be killed by lysostaphin after penetration of the cells during incubation or by adhering lysostaphin when the monocytes are disrupted.

Adhesiveness↗