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Biomedical subjects

R van Furth

Publications and source records attributed to R van Furth.

At least 253 records · Page 14Linked to original sources
PubMed1984

Effect of concanavalin A on intracellular killing of Staphylococcus aureus by human phagocytes.

This study concerns the influence of concanavalin A (Con A) on phagocytosis and intracellular killing of Staphylococcus aureus by human monocytes and granulocytes. Con A binds to S. aureus, monocytes, and granulocytes, and is not opsonic. Con A stimulates the killing of intracellular serum opsonized S. aureus by monocytes, but not by granulocytes. This stimulation of intracellular killing was inhibited by alpha-methyl-mannoside, indicating that the process occurs via Con A specific membrane binding sites. Unlike (tetravalent) Con A, divalent succinyl-Con A does not stimulate intracellular killing, indicating that the lectin valency is important for this stimulation. Con A bound to Sephadex particles, that can not be ingested by monocytes, does not stimulate intracellular killing of S. aureus either, although it, like free Con A, stimulates H2O2 production. Pre-incubation of monocytes with Con A inhibited Fc gamma and C3b-mediated ingestion of S. aureus as well as stimulation of the killing by serum. Divalent Con A had no effect on these functions. This inhibition by Con A is in all probability due to a steric impedance of Con A with respect to the interaction of IgG and C3b with their membrane receptors. Fluorescence techniques showed that Con A was localized on the membrane and in the cytoplasm of the monocytes, whereas granulocytes had only membrane bound lectin. Taken together, these findings suggest that cell penetration by the lectin is obligatory for the stimulation of intracellular killing.

Blood Bactericidal Activity↗
PubMed1983

Current views on the ontogeny of macrophages and the humoral regulation of monocytopoiesis.

Macrophages do not constitute a stable population but are constantly renewed by an influx of monocytes and by local division of immature mononuclear phagocytes that have also recently arrived in the tissues. The calculated mean turn-over time of tissue macrophages lies between four and six days. During an inflammatory response the production of monocytes in the bone marrow is increased. This process is regulated by a humoral factor, FIM, which is formed and secreted by tissue macrophages. The response of monocyte precursors to FIM is under genetic control.

Animals↗
PubMed1983

Legionella pneumonia in guinea pigs exposed to aerosols of concentrated potable water from a hospital with nosocomial Legionnaires' disease.

An investigation of an outbreak of nosocomial legionella pneumonia revealed that the potable water of the hospital was contaminated with a distinctive strain of Legionella pneumophila (designated the Le-1 strain), which was by culture and serology linked with human illness. To examine the possible role of this water in this outbreak, eight healthy guinea pigs were exposed to an aerosol of concentrated potable water. Seven animals developed pneumonia due to the Le-1 strain of L. pneumophila. In one of these guinea pigs, the Le-1 strain was also isolated from the blood and spleen. These results provide support to the theory that exposure of humans to aerosols of potable water contaminated with L. pneumophila may cause legionella pneumonia.

Aerosols↗
PubMed1983

Selective antimicrobial modulation of the intestinal flora of patients with acute nonlymphocytic leukemia: a double-blind, placebo-controlled study.

Thirty-three patients with acute nonlymphocytic leukemia were studied during remission-induction treatment in a double-blind, placebo-controlled, randomized study to ascertain the effect on the incidence of infection of an oral regimen of selective antimicrobial modulation (SAM). A decrease in the number of major acquired infections was observed: three infections occurred in 16 patients receiving the SAM regimen compared with eight infections in 17 patients given the placebo. The reduction of infection was correlated with a reduction of fever, with a reduction of the frequency of administration of antimicrobial agents for the treatment of infection, and with the selective elimination of aerobic and facultative anaerobic gram-negative rods from the digestive tract. Substantial unfavorable side effects were not observed.

Adolescent↗
PubMed1983

Role of granulocytes and monocytes in experimental Staphylococcus epidermidis endocarditis.

The role of granulocytes and monocytes during the induction and course of Staphylococcus epidermidis endocarditis was investigated by the selective depletion of monocytes with the drug VP16-213 and of both granulocytes and monocytes with nitrogen mustard. The induction of endocarditis was influenced only by the depletion of monocytes: the 50% infective dose differed significantly, being 3.4 X 10(5) CFU in control rabbits and 3.4 X 10(4) CFU in the monocyte-depleted rabbits, whereas no significant differences were found between the latter and those depleted of both granulocytes and monocytes. Also, control rabbits injected with 10(6) or 10(7) CFU had a significantly higher incidence of sterile vegetations than did rabbits selectively depleted of granulocytes or monocytes. Compared with baseline values, mean monocyte numbers at the time of bacterial inoculation were significantly increased in control rabbits whose vegetations remained sterile, whereas this effect was not seen in rabbits whose vegetations became infected. The course of the endocarditis appeared to be significantly influenced by both granulocytes and monocytes. Comparison showed that a decrease of the same numbers of these cells per microliter of blood was accompanied for the monocytes by an approximately fourfold higher increase of the number of staphylococci in the vegetations. The correlation between the number of granulocytes and of monocytes on the one hand and the number of staphylococci in the vegetations on the other was not substantially influenced by the duration of the disease or the number of staphylococci injected to induce the endocarditis. The number injected proved to be significantly correlated with the number of staphylococci in the vegetations. In rabbits with numbers of CFU per gram of vegetation exceeding 10(7), blood cultures were usually positive. This finding applied rarely to control rabbits, but generally to drug-treated rabbits. In the latter animals a significant correlation between the number of staphylococci in the vegetations and in the circulation was found. We conclude that only monocytes have a measurable effect on the induction of Staphylococcus epidermidis endocarditis but during its course both granulocytes and monocytes keep the endocardial infection in check.

Animals↗
PubMed1983

The antibacterial activity of combinations of mecillinam and ampicillin in vitro and in normal and granulopenic mice.

The antibacterial activity of mecillinam and ampicillin, alone and in combination, against Escherichia coli was quantitated and compared in vitro and in vivo. Minimum inhibitory concentrations (MICs) were determined for both antibiotics individually and combined. Two-hour growth curves were established in vitro. A quadratic fit to these growth curves provided quantitative concentration-dependent growth characteristics. The antibacterial activity in vivo was determined by applying a short-term thigh muscle infection model to normal and irradiated granulopenic mice. The effects in vivo were also quantitated as dose-dependent or concentration-dependent parameters. Mecillinam showed activity in vitro, but none in vivo. Combinations of mecillinam with ampicillin showed a strong potentiation, as judged from MICs and from short-term experiments in vitro and in the normal and irradiated granulopenic mice. The potentiating activity in vivo was not influenced by host factors (i.e. granulocytes). However, the degree of potentiation indicated by the MICs led to strong overestimation of the effect of the combination of the two antibiotics on short-term in vitro growth. Furthermore, the combined activity in vitro overestimated the potentiating effect of the two antibiotics in vivo.

Amdinocillin↗
PubMed1983

Comparison of in vitro and in vivo ampicillin susceptibility of Escherichia coli pretreated with low concentrations of mecillinam and ampicillin.

The ampicillin susceptibility of Escherichia coli showing morphological changes after pretreatment with low concentrations of mecillinam (spherical forms) or ampicillin (filaments) was compared in vitro and in vivo in short term experiments. Normal non-pretreated bacteria and mecillinam- or ampicillin-pretreated bacteria were cultured in vitro in the presence and absence of ampicillin. The growth curves were mathematically described as quadratic functions of time and these functions provided parameters characterizing the growth kinetics. The mecillinam pretreatment did not affect the growth rate relative to that of normal non-pretreated bacteria. The ampicillin susceptibility of these mecillinam-pretreated forms was, however, strongly increased. The ampicillin pretreatment resulted in an increased initial growth rate of the bacteria which normalized after about 1 1/2 h. The ampicillin susceptibility of these bacteria was unchanged. The growth and the ampicillin susceptibility of these ampicillin- or mecillinam-pretreated bacteria in an intramuscular infection in irradiated granulopenic mice were comparable with those seen in vitro. This outcome in vivo was influenced by the granulocytes when growth and ampicillin susceptibility were determined in non-irradiated mice. The mecillinam-pretreated bacteria were slightly more affected by both granulocytes and ampicillin than normal bacteria were. The ampicillin-pretreated bacteria were affected by both these factors to the same extent as normal bacteria.

Amdinocillin↗
PubMed1983

Cytochemical, functional, and proliferative characteristics of promonocytes and monocytes from patients with monocytic leukemia.

This article deals with a prospective study on the cytochemical, functional, and proliferative characteristics of promonocytes and bone marrow and peripheral blood monocytes of 20 patients with acute monocytic leukemia and 7 patients with chronic monocytic leukemia. The results show a wide variation in the peroxidase and esterase activities in these cells, whereas the percentages of mononuclear phagocytes with Fc gamma and C3b receptors did not differ appreciably from those in normal individuals. A discriminant analysis of these data and corresponding data from normal individuals showed that a below-normal peroxidase activity of circulating monocytes has predictive value for the presence of monocytic leukemia; a below-normal esterase activity has less, but nevertheless some, predictive value in this respect. An increase in the percentage of circulating monocytes, a decrease in the percentage of Fc gamma or C3b receptors, and a decline in the ability to phagocytose bacteria has no predictive value for the presence of monocytic leukemia. The mean percentage of patients' promonocytes that incorporated 3H-thymidine amounted to 80.9%, which is close to the control value in normal individuals. The mean values for the labeling indices of cultured bone marrow and peripheral blood monocytes are 1.0% and 0.74%, respectively; when 3H-thymidine was added to whole blood, the labeling index of the monocytes amounted to 3.6%. These percentages are only a little higher than those found for monocytes of normal individuals. These results indicate that the majority of the circulating monocytes in acute and chronic monocytic leukemia are not actively dividing or blast cells.

Bone Marrow Cells↗
PubMed1983

Synthesis of alpha 1-anti-trypsin by human monocytes.

The present report concerns the site of synthesis of alpha 1-anti-trypsin (alpha 1 AT). In this study circulating cells and tissue fragments were incubated with radioactive amino acids to be incorporated during protein synthesis. The de novo synthesis of proteins was demonstrated by autoradiography of the immunoelectrophoretic slide. The results constitute proof that alpha 1 AT is formed by circulating human monocytes and support those obtained in earlier immunofluorescent studies which showed that alpha 1 AT is present in pulmonary macrophages, as could be expected because these cells derive from circulating monocytes. The culture fluid of liver tissues also showed labelled alpha 1 AT, but it is not clear whether in this organ alpha 1 AT is formed by Kupffer cells and/or parenchymal cells.

Cell Line↗
PubMed1983

Characteristics of long-term cultures of proliferating, mononuclear phagocytes from bone marrow.

The characteristics of murine bone marrow mononuclear phagocytes in long-term cultures with embryonic fibroblast-conditioned medium were studied to determine the stage of development and state of activation of these cells. Two liquid culture systems were used: for studies on the morphology, cytochemistry, and functional characteristics at the cellular level, the cells were cultured adherent to a glass surface; and for experiments where the cells were needed in suspension (replating experiments, and studies on locomotion, intracellular killing, and cytotoxicity) use was made of Teflon culture systems. Three developmental stages of mononuclear phagocytes could be recognized easily in these cultures: monoblasts, promonocytes, and macrophages. In cultures on a glass surface, these cells grow in colonies separate from granulocytic colonies. When incubation is prolonged beyond 7-9 days, the granulocytes die, leaving pure mononuclear phagocyte cultures. Primary cultures, in which monoblasts, promonocytes, and some macrophages proliferate, can be maintained for 3-4 weeks. Calculation showed that one monoblast present on day 0 gives rise to a progeny of more than 7 X 10(3) mononuclear phagocytes by day 14; after that, the rate of proliferation declines despite the addition of fresh media. Regular replating of the cells cultured on Teflon made it possible to maintain proliferation over a period of almost 200 days. The cells in culture have the typical characteristics of mononuclear phagocytes, as judged by light microscopy, alpha-naphthyl butyrate esterase activity, lysozyme activity, presence of receptors for Fc and C3, and endocytic, microbicidal, and cytotoxic activity. The 5'nucleotidase activity, ingestion of erythrocytes via C3-receptor, locomotion, and antibody-dependent cytotoxicity indicate that the cultured bone marrow mononuclear phagocytes are more active than resident macrophages, and as active as or even more active than thioglycollate-induced macrophages. In conclusion, the population of mononuclear phagocytes in the liquid cultures of bone marrow is heterogenous with respect to developmental stage and state of activation.

Animals↗