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Biomedical subjects

R van Furth

Publications and source records attributed to R van Furth.

At least 181 records · Page 10Linked to original sources
PubMed1988

Roles of factor increasing monocytopoiesis (FIM) and macrophage activation in host resistance to Listeria monocytogenes.

The present contribution concerns two aspects of host resistance in overcoming an infection with Listeria monocytogenes. One of these aspects is the regulation of monocyte production by the factor increasing monocytopoiesis (FIM), a macrophage-derived factor. Listeria-resistant (C57BL/10 mice and Listeria-sensitive CBA mice produce and secrete similar amounts of FIM in response to an inflammation induced by soluble Listeria antigen. However, monocyte precursors in the bone marrow of Listeria-resistant mice react to an injection of serum containing FIM by increased monocyte production, whereas Listeria-sensitive mice are unable to react to this stimulus. The other aspect of host resistance to L. monocytogenes is the activation of macrophages leading to increased bactericidal activity. Macrophages of both mouse strains stimulated first with live BCG and then with PPD, killed ingested Listeria faster than resident peritoneal macrophages did. However, recombinant interferon-gamma, thought to be the most important macrophage-activating factor, did not induce increased listericidal activity in macrophages.

Animals↗
PubMed1988

Contribution of granulocytes and monocytes to resistance against experimental disseminated Candida albicans infection.

The aim of the present study was to investigate the contribution of granulocytes and monocytes to resistance against an acute systemic candidal infection in mice. To this end granulocytopenia and monocytopenia were induced by irradiation or treatment with cyclophosphamide, and monocytopenia was obtained by treatment with VP-16. After intravenous injection of 1 X 10(4) Candida albicans into mice irradiated with 8 GY, the number of Candida albicans cultured from the kidneys, expressed as the geometric mean of the number of CFU/g tissue, was 5.4 X 10(4), 7.1 X 10(6) and 5.8 X 10(7) on days 1, 3 and 5 of infection respectively (p less than 0.001 compared to normal mice). The number of Candida albicans cultured from the liver and spleen was also significantly higher for irradiated animals than for normal mice (p less than 0.001). For cyclophosphamide-treated mice the number of organisms in the kidney (1.7 X 10(4) CFU/g on day 1, 1.9 X 10(6) on day 3 and 3.8 X 10(6) on day 5 of infection) and spleen was significantly higher (p at least less than 0.02) than for normal mice after injection of 1 X 10(3) Candida albicans. Monocytopenia induced by VP-16 did not result in an increase in the number of Candida albicans cultured from the kidney or spleen after infection. From these studies it is concluded that granulocytes and not monocytes or exudate macrophages play an important role in resistance against Candida albicans during the first five days of a systemic infection.

Animals↗
PubMed1988

Quantitative immunocytochemical characterization of four murine macrophage-like cell lines.

The aim of the present study was to obtain quantitative data on the expression of seven cell-surface antigens by the murine macrophage-like cell lines WEHI-3, P388-D1, J774.1, and PU5-1.8, and to compare these data with those obtained for various mononuclear phagocytes. Binding of monoclonal antibodies F4/80, M1/70, 2.4.G.2., 30.G.12, M3/38, M3/84, and 59AD2.2 to cells from these four cell lines was detected by the biotin-avidin immunoperoxidase staining method and quantified by cytophotometry. The results are expressed as the percentage cells expressing a given antigen and the mean specific integrated absorbance per 0.25 micron2 cell-surface area. The results revealed that the phenotypes of the four macrophage-like cell lines differ markedly. Expression of the cell antigens by the cells of the various cell lines did not follow a normal distribution. Although the cell lines divide continuously and have certain characteristics in common with mature mononuclear phagocytes, none of the macrophage-like cell lines accurately resembles any of the mononuclear phagocyte populations. The strongest correlations for membrane were found between on the one hand WEHI-3 and P388-D1 cells and monoblasts and promonocytes (P greater than 0.011) on the other. P388-D1, J774.1 and PU5-1.8 cells expressed four of the six antigens to the same extent as skin macrophages (P greater than 0.012). With respect to expression of antigens recognized by antibodies 2.4.G.2., 30.G.12, M3/38, and M3/84 PU5-1.8 cells resembled activated peritoneal macrophages (P greater than 0.031). It is concluded that WEHI-3 is the most immature cell line, followed by the P388-D1 cell line, while J774.1, and PU5-1.8 are the most mature cell lines.

Animals↗
PubMed1988

Phagocytosis by human macrophages is accompanied by changes in ionic channel currents.

The present study has shown that changes in ionic channel currents accompany the phagocytosis of particles by mononuclear phagocytes. The patch-clamp technique in the cell-attached configuration was applied to human monocyte-derived macrophages to measure the activity of single transmembrane ionic channels in intact cells. During such measurements, IgG-opsonized and non-opsonized latex particles were offered for phagocytosis under continuous video-microscopical observation. Single particles were presented to the phagocytes at a membrane location some distance from that of the patch electrode. After a lag period following particle attachment, enhanced inward and outward time-variant single channel currents coinciding with particle engulfment were observed. On the basis of current-voltage characteristics and membrane potential measurements, the outward-directed channels were identified as K+ channels. Phagocytosis was also accompanied by slow transient changes in background membrane currents, probably due to changes in the membrane potential of the phagocytosing cell. Phagocytosis of IgG-coated latex particles differed from phagocytosis of uncoated or albumin-coated particles by a shorter lag time between particle attachment and the onset of enhanced ionic channel activity.

Electric Conductivity↗
PubMed1988

Effects of tissue-type plasminogen activator (t-PA) on Streptococcus sanguis-infected endocardial vegetations in vitro.

The effects were studied of in-vitro exposure to tissue-type plasminogen activator (t-PA) on endocardial vegetations isolated from rabbits with Streptococcus sanguis endocarditis as well as on Str. sanguis-infected plasma clots. For both vegetations and clots t-PA induced lysis of the infected fibrin matrix, demonstrated by a release of streptococci into the incubation medium and by an increase in the concentration of fibrin degradation products. The clots decreased in weight, whereas only partial lysis of the vegetations was obtained. Addition of plasminogen to the incubation medium did not enhance the effect of t-PA on vegetations. Fibrinolysis by t-PA did not interfere with the antimicrobial action of benzylpenicillin on the bacteria in a fibrin matrix. It is concluded that t-PA can degrade the fibrin matrices of infected endocardial vegetations and plasma clots. Reduction of vegetation size by t-PA may prove to be useful in the treatment of bacterial endocarditis.

Animals↗
PubMed1988

A prospective study of the efficacy of fluconazole (UK-49,858) against deep-seated fungal infections.

Fluconazole (UK-49,858) is a new bis-triazole antifungal drug that can be administered both orally and intravenously. We conducted an open clinical trial on the efficacy of fluconazole (50-100 mg) once daily in 20 non-neutropenic patients with deep-seated fungal infections. Seventeen patients (eight females, nine males, median age 56 years) could be evaluated clinically. All patients had an underlying disease, while eight also received immunosuppressive therapy. The median duration of treatment was 33 days (range 8-194 days). Clinical cure or improvement was achieved in 14 of 17 patients (82%). Nine patients were both clinically and microbiologically cured. Fluconazole was especially effective in patients with candidal infections. Two patients with cryptococcal meningitis were clinically cured; one of the two was also microbiologically cured. No serious side effects of fluconazole were encountered.

Adolescent↗
PubMed1988

Antibacterial effect of etoposide in vitro.

Etoposide, an antitumor drug, had an effect in vitro against all strains of gram-positive bacteria studied but not against three gram-negative bacteria. The MICs ranged between 6.2 and 50 micrograms/ml. In short-term-growth experiments, etoposide had a bactericidal efficacy that was 10 to 50 times lower than that of cloxacillin.

Etoposide↗
PubMed1988

Characteristics of anti-Legionella antibodies in patients infected with Legionella pneumophila serogroups 1, 6, and 10.

Nosocomial infections with Legionella pneumophila serogroups 1 and 10 in the Leiden University Hospital and infections with L. pneumophila serogroup 6 in neighboring hospitals gave us an opportunity to study the development of opsonizing antibodies against L. pneumophila serogroups 1, 6, and 10 in the serum of 13 patients. Seven of these patients were infected with L. pneumophila serogroup 1, two were infected with serogroup 6, and four were infected with serogroup 10. The opsonic cross-reactivity of antibodies against these serogroups of L. pneumophila and complement involvement in opsonization were also investigated. Convalescent-phase sera from patients infected with L. pneumophila serogroup 1 or 6 were able to promote ingestion of these serogroups by polymorphonuclear leukocytes, whereas ingestion of L. pneumophila serogroup 10 was enhanced only in the presence of convalescent-phase sera from patients infected with this serogroup. Opsonization of L. pneumophila serogroups 1, 6, and 10 was complement dependent.

Antibodies, Bacterial↗
PubMed1988

Treatment of two cases of cryptococcal meningitis with fluconazole.

Two patients with cryptococcal meningitis were treated with the investigational triazole drug fluconazole (UK-49,858). Cerebrospinal fluid (CSF) levels of fluconazole were between 3.0 and 5.4 mg/l 2 h after an oral dose of 50 mg daily in the first patient and between 7.9 and 9.0 mg/l after an oral dose of 100 mg daily in the second patient. These levels were in the same range as plasma levels. The first patient, a 46-year-old renal transplant patient, was both clinically and microbiologically cured after 28 weeks of therapy (follow-up 14 months). In the second patient, a 15-year-old girl with chronic mucocutaneous candidiasis, fluconazole led to clinical cure of the meningitis, but failed to eradicate cryptococci from the CSF. These cases illustrate that fluconazole is useful for the treatment of cryptococcal meningitis, especially when prolonged treatment is indicated as in patients with immunodeficiencies.

Adolescent↗
PubMed1988

Antibiotic prophylaxis in craniotomy: a prospective double-blind placebo-controlled study.

A prospective double-blind placebo-controlled study was performed to evaluate the efficacy of cloxacillin for the prevention of infections after craniotomy. 310 patients were admitted to the study. 39 died within 90 days after craniotomy without an infection, 20 and 19 of them belonging to the cloxacillin and placebo groups, respectively. In the cloxacillin group 6 neurosurgical infections occurred after 183 operations (3.3%) in 156 patients (3.9%), and in the placebo group 20 after 195 operations (10.3%) in 154 patients (13%). These differences between the 2 groups are statistically significant (p less than 0.01 and p less than 0.05 for patients and operations, respectively). For a craniotomy subgroup, there was no significant difference in infection rate between the cloxacillin and placebo groups. We conclude that cloxacillin significantly reduces the rate of infection after craniotomy, and recommend administration of this antibiotic for prophylaxis in patients undergoing this operation.

Adolescent↗
PubMed1988

The efficacy of rifampicin against Staphylococcus aureus in vitro and in an experimental infection in normal and granulocytopenic mice.

The effect of rifampicin on Staphylococcus aureus in vitro was assessed as the difference between the logarithms of the numbers of colony forming units (CFU) with and without 3 h of exposure to the drug. The efficacy was expressed as the EC50, i.e. the concentration at which 50% of the maximal effect was obtained, calculated according to the Hill equation. The value found for the EC50 was 3.8 micrograms/l and the mean maximal effect was a log ratio of 5.03 (SEM 0.33). In vivo experiments were performed in normal mice and in mice made granulocytopenic by irradiation. The effect of rifampicin was assessed as the CFU count 5 h after the injection of a suspension of bacteria into the thigh muscle and 4 h after the administration of rifampicin. The efficacy was expressed as the ED50, i.e. the dose at which 50% of the maximal effect is obtained. This value was 0.18 mg/kg for the normal mice and 0.15 mg/kg for the granulocytopenic mice. The corresponding mean plasma concentrations of non-protein-bound drug were 28 and 24 mg/l, respectively. Thus, the EC50 was found to be much higher in vivo than that in vitro. This difference should be taken into account when parameters of in-vitro efficacy are applied to establish dosage schedules.

Agranulocytosis↗
PubMed1988

In vitro synthesis of immunoglobulins in cutaneous leishmaniasis.

In an in vitro study, IgG was synthesized in large amounts by tissue from cutaneous leishmaniasis lesions. IgA and IgM were produced in the minority of the cultures in distinct and small amounts, respectively. Synthesis of complement (C3 and C4) could not be detected, but lysozyme was produced sporadically. The significance of these findings is discussed.

Animals↗
PubMed1988

In vitro synthesis of antimycobacterial antibodies with different specificities in various tissues of leprosy patients.

For the detection of the synthesis in vitro of anti-Mycobacterium leprae antibodies in various tissues of leprosy patients, biopsy specimens of skin lesions, nasal mucosa, larynx, lymph nodes, and bone marrow were cultured in a medium containing 14C-labeled lysine and isoleucine. The culture fluids were analyzed by crossed immunoelectrophoresis with intermediate gel and autoradiography. The results show that synthesis of anti-M. leprae antibodies occurs at the investigated sites of leprosy patients and that the specificities of the synthesized antibodies differ between sites in individual patients. It is conceivable that these antibodies play a role in the local defense against M. leprae.

Antibodies, Bacterial↗
PubMed1988

Effect of lung surfactant on the release of factor increasing monocytopoiesis by macrophages.

Upon ingestion of particulate and soluble material, at the site of an inflammation macrophages release the factor increasing monocytopoiesis (FIM), which accelerates the rate of division of the monoblasts and promonocytes in the bone marrow. It is not known, however, whether FIM is released by macrophages present at noninflamed sites. Since FIM is secreted only during phagocytosis and alveolar macrophages ingest surfactant in vivo, the present study was performed to find out whether surfactant induces the release of FIM by alveolar macrophages. Resident alveolar macrophages were found to contain FIM and secrete this factor in vitro in the absence of an introduced phagocytable particle. Resident peritoneal macrophages also contained FIM and released this factor after exposure to surfactant. These findings suggest that in the absence of an inflammatory stimulus in vivo, alveolar macrophages that have ingested surfactant release FIM to maintain the normal production of monocytes in the bone marrow.

Animals↗
PubMed1987

Macrophages as origin of factor increasing monocytopoiesis.

Earlier investigations had indicated that the factor increasing monocytopoiesis (FIM), present in the serum of mice and rabbits during the onset of an inflammatory response, is released by cells of the inflammatory exudate. The present study was performed to determine which cells produce and secrete this factor and to establish the kinetics of its production and secretion. FIM was assayed in vivo by intravenous injection of samples into untreated mice and monitoring the course of the number of blood monocytes in the recipients. FIM was assayed in vitro by adding samples to cultures of the macrophage cell line PU5 and determining the rate of proliferation of the cells. The results show that only macrophages contain and synthesize FIM. This factor is secreted upon exposure to a phagocytic stimulus, and after the release of preformed FIM, macrophages secrete newly synthesized FIM. Granulocytes and lymphocytes neither contain nor secrete FIM. The characteristics of FIM derived from macrophages are in all aspects similar to those of FIM in serum. Macrophage-derived FIM is a protein with a molecular weight between 10 and 25 X 10(3), its activity is cell-lineage specific and dose dependent, and it stimulates monocyte production in the bone marrow. Macrophage-derived FIM is not identical to either CSF-1 or IL-1, and has no chemotactic activity. Taken together, the present results show that FIM occurring in serum during an inflammatory response originates from macrophages at the site of the inflammation. In this way the macrophages themselves regulate the supply of circulating blood monocytes that can migrate to the site of injury when needed.

Animals↗
PubMed1987

Divergent changes in antimicrobial activity after immunologic activation of mouse peritoneal macrophages.

To find out whether activated macrophages display a nonspecific enhancement of antibacterial activity, we determined the intracellular killing of bacteria by peritoneal macrophages from CBA and C57BL/10 mice infected with BCG and challenged with mycobacterial antigens (purified protein derivative (PPD]. After in vivo phagocytosis, the rate of in vitro intracellular killing of Listeria monocytogenes by bacillus Calmette-Guérin (BCG)-PPD-activated macrophages from CBA mice increased by a factor of 1.7 and that of those from C57BL/10 mice by a factor of 2.0, relative to the rate in normal resident macrophages. The increased listericidal activity of BCG-PPD-activated macrophages could not have been due to an increased number of peroxidase-positive macrophages because exudate macrophages obtained after i.p. injection of proteose peptone into BCG-infected mice or PPD into control mice, killed ingested Listeria about as efficiently as normal resident macrophages did. In contrast, BCG-PPD-activated macrophages from both mouse strains killed Salmonella somewhat less efficiently and Escherichia coli and Staphylococcus aureus with the same efficiency as normal resident macrophages did. These cells, however, inhibited the intracellular replication of Toxoplasma gondii. Activated peritoneal macrophages from listeria-infected mice showed a similar increase of the rate of intracellular killing of Listeria and absence of change in rate of intracellular killing of Salmonella. Consistent with the in vitro findings, the number of viable L. monocytogenes in the spleen and liver of BCG-infected CBA and C57BL/10 mice decreased during the first 2 days after i.v. injection, whereas Salmonella typhimurium proliferated in these organs of both mouse strains. Checking the state of activation of BCG-PPD-activated macrophages showed that these cells displayed enhanced O2-consumption and H2O2 release after stimulation with phorbol myristate acetate compared with resident macrophages. The present findings show that the antimicrobial activity of immunologically activated macrophages is not uniformly increased: for certain microorganisms (L. monocytogenes, T. gondii), this effector function is enhanced, whereas for others (S. typhimurium, S. aureus, E. coli), it is not.

Animals↗
PubMed1987

Inability of recombinant interferon-gamma to activate the antibacterial activity of mouse peritoneal macrophages against Listeria monocytogenes and Salmonella typhimurium.

The effect of recombinant murine interferon-gamma (rIFN-gamma) as single stimulus for the activation of antibacterial activity of macrophages was investigated on the basis of the rate of intracellular killing of Listeria monocytogenes and Salmonella typhimurium by normal and rIFN gamma-activated peritoneal macrophages of CBA and C57BL/10 mice, which differ in natural resistance to infection by these bacteria. Eighteen hours after i.p. injection of 10 to 1 X 10(4) U rIFN-gamma, resident and exudate peritoneal macrophages which had phagocytosed L. monocytogenes or S. typhimurium in vivo, killed both species in vitro just as efficiently as did resident macrophages of normal mice. Similar results were obtained after 18 hr of in vitro incubation of resident or exudate peritoneal macrophages with 0.1 to 1 X 10(4) U/ml rIFN-gamma. Consistent with the in vitro findings, two i.v. injections of 5 X 10(4) U rIFN-gamma did not affect the rate of in vivo proliferation of L. monocytogenes or S. typhimurium in the spleens of mice during the first 2 days after i.v. injection of the bacteria. Compared with the effect on the controls, two i.p. injections of 5 X 10(2) to 5 X 10(4) U rIFN-gamma did not decrease the numbers of viable S. typhimurium in either the peritoneal cell suspension or the spleen 24 hr after i.p. injection of the bacteria. Checking the state of activation of rIFN-gamma-activated macrophages on the basis of two commonly used criteria for macrophage activation showed that rIFN-gamma-activated macrophages inhibited the intracellular replication of Toxoplasma gondii and displayed enhanced O2 consumption and H2O2 release after stimulation with phorbol myristate acetate compared with macrophages from normal CBA and C57BL/10 mice. The present findings show that as single activating stimulus, rIFN-gamma is not capable of activating the antibacterial effector functions of peritoneal macrophages against facultative intracellular pathogens such as L. monocytogenes and S. typhimurium.

Animals↗