Many organisms use multimodal maps to generate coherent neuronal representations that allow adequ... more Many organisms use multimodal maps to generate coherent neuronal representations that allow adequate responses to stimuli that excite several sensory modalities. During ontogeny of these maps, one modality typically acts as the dominant system the other modalities are aligned to. A well studied model for the alignment of sensory maps is the calibration of the auditory space map by the visual system in the optic tectum of the barn owl. However, a projection from the optic tectum to the site of plasticity in the auditory pathway that could deliver an instructive signal has not been found so far. We have analyzed the development of the connectivity between the bimodal (vi-sual and auditory) map of space in the barn owl's optic tectum and the auditory space map in the inferior colliculus with tracing methods and intracellular fills. Neurons in the tectal stratum griseum centrale were found to be suited to deliver an alignment signal from the visual midbrain to the auditory pathway. These neurons are presumably part of the efferent tectal projection pathway that mediates head saccades. The implications of a sensory alignment signal possibly being delivered by a (pre)motor command pathway are discussed.
A limiting-diluiion system was established to measure the frequency of alloreactive cytotoxic T-l... more A limiting-diluiion system was established to measure the frequency of alloreactive cytotoxic T-lymphocyte precursors(CTL-p) in human poripherii! bl<K>dTcells. Culture medium supplemenicd with recombinant interleukin-2 enabled elonal expansion of all CTL-p sumulatcd by aUogeneic peripheral blood or spleen cells. The range of CTL-p frequencies in fully HLAmismaieheci responiier-stimulatnr combinatiotis was 1;24() to 1:1230. Splil-well analysis of individual niicrowclls showed that the cytotoxic T-ccll clones generated under limiting-dilution conditions showed exquisite specificity for the stitnulating alloantigens. Alloreactive CTL-p were enriched in the <)KT4 T-cell subset. This limiting-dilution system was highly reproducible and cati thus be applied to investigate human eytoloxic T-eeM precursor frequencies in various tiiniailly relevant situations.
The influence of niridazole, an anti-helminthic drug, on cell-mediated immune responses was inves... more The influence of niridazole, an anti-helminthic drug, on cell-mediated immune responses was investigated. Allograft rejection in mice as well as the in vitro induction of cytotoxic T lymphocytes (CTL) against murine alloantigen were used as the test system. Repeated daily oral treatment of host mice with niridazole (100 mg/kg) prior to and during allotransplantation resulted in the postponement of graft rejection, inducing a transitory functional state of allograft tolerance. The time interval between the termination ofniridazole administration and onset ofgraft rejection was estimated to be 5-7 days.
In the model system used here, cross-linking of T-cell receptor structures (TCR) by antigenpresen... more In the model system used here, cross-linking of T-cell receptor structures (TCR) by antigenpresenting cells (APCs) is substituted by the use of anti-F23.1 anti-T-cell receptor monoclonal antibody immobilized on Sepharose beads. We show that CR cross-linking of resting murine CD8+ T cells seeded at low cell densities is insufficient to induce responsiveness to the growth-promoting effect of interleukin-2 (IL-2), i.e. fails to induce expression of functional IL-2 receptors. The macrophage cell-line product, IL-2 receptor-inducing factor (RIF), but not IL-1, IL-3, IL4 and interferongamma (IFN-y) functions efficiently as a co-stimulator. Once activated, growth of CD8+ T cells is driven entirely by IL-2. We conclude that two restriction points control the activation of resting CD8+ T cells. While cross-linking of TCR is essential as the first step, RIF is required as the competence factor to induce IL-2 responsiveness. We consider the possibility that the ability of APCs to produce RIF determines the immunogenicity of APCs towards antigen-reactive resting CD8+ T cells.
Colonization of the oropharynx with potentially pathogenic microorganisms (PPM) is a highly signi... more Colonization of the oropharynx with potentially pathogenic microorganisms (PPM) is a highly significant factor in the pathogenesis of bacterial pneumonia in intensive care patients. Via colonization of the oropharynx, bacteria pass into the tracheobronchial tree, where they can give rise to pneumonia after overcoming pulmonary resistance mechanisms. By a new, prophylactic antibiotic treatment schedule consisting in selective decontamination of the digestive tract (SDD) with locally applied nonabsorbable antibiotics, Stoutenbeek achieved drastic lowering of the colonization and infection rate in trauma patients. In the present study, we wanted to check whether this new prophylactic antibiotic schedule can be applied on a surgical intensive care ward in all patients with long-term ventilation, irrespective of the diagnosis, and whether it affords advantages over a conventional antibiotic schedule. MATERIALS AND METHODS. All patients on a surgical intensive care ward in whom it was expected that mechanical ventilation would be necessary for more than 4 days were included in the study. During the first 6 months 83 patients were investigated, in whom antibiotics were only administered when the presence of infection had been confirmed, in accordance with generally accepted guidelines (control group). In the second 6-month period, 82 patients were selectively decontaminated with 4 x 100 mg polymyxin E, 4 x 80 mg tobramycin and 4 x 500 mg amphotericin B, administered through the gastric tube and in an antimicrobial paste in the oropharynx (SDD group). The SDD schedule entailed systemic administration of cefotaxime in the first 3-4 days. RESULTS. In the control group, enterobacteria/Pseudomonas spp. were isolated significantly more frequently than in the SDD group (P less than 0.001): in the pharyngeal smear in up to 53%, in the tracheal secretion up to 36%, and in the rectal smear in up to 93% of the patients In the SDD group in the 1 week the frequency of gram-negative aerobic bacteria in the pharynx decreased from 33% to 5%, in the tracheal secretion from 23% to 14% and in the rectum from 86% to 52% (24% in the second week). However, the decrease in gram-negative microorganisms was accompanied by significant increase in the frequency of Staphylococcus epidermidis and enterococci. The SDD schedule proved to be effective with regard to the rate of infection. In the control group, 35 patients developed pneumonia (42%) as against 5 patients receiving SDD prophylaxis (6%). The duration of mechanical ventilation in the patients with pneumonia was 5 days longer than in patients without pneumonia.(ABSTRACT TRUNCATED AT 400 WORDS)
In this work we study the role of subsets of human T cells, detectable by the OKT series of monoc... more In this work we study the role of subsets of human T cells, detectable by the OKT series of monoclonal antibodies, in the production of and the response to the lymphokine interleukin-2 (11-2) during the course of an allogeneic cytotoxic T lymphocyte response in vitro. The results obtained establish that the 11-2 producer cells reside within the OKT4 positive T cell subset. Once produced, I1-2 mediates the clonal expansion of alloantigenactivated cytotoxic T killer cells which reside in the OKT8 positive T cell subset. 11-2 appears to have no mitogenic activity on the activated OKT4 positive T cells which produce the lymphokine. In order to release I1-2, the OKT4 positive T cell requires a stimulus, such as allogeneic cells or the lectin phytohaemagglutinin A (PHA). Macrophages are also required for I1-2 production, but the macrophage requirement can be bypassed by a soluble macrophage product as found in supernatants of lymphocyte cultures stimulated with lipopolysaccharide (LPS), the biological activity presumably representing Interleukin-1 (Il--).
Many organisms use multimodal maps to generate coherent neuronal representations that allow adequ... more Many organisms use multimodal maps to generate coherent neuronal representations that allow adequate responses to stimuli that excite several sensory modalities. During ontogeny of these maps, one modality typically acts as the dominant system the other modalities are aligned to. A well studied model for the alignment of sensory maps is the calibration of the auditory space map by the visual system in the optic tectum of the barn owl. However, a projection from the optic tectum to the site of plasticity in the auditory pathway that could deliver an instructive signal has not been found so far. We have analyzed the development of the connectivity between the bimodal (vi-sual and auditory) map of space in the barn owl's optic tectum and the auditory space map in the inferior colliculus with tracing methods and intracellular fills. Neurons in the tectal stratum griseum centrale were found to be suited to deliver an alignment signal from the visual midbrain to the auditory pathway. These neurons are presumably part of the efferent tectal projection pathway that mediates head saccades. The implications of a sensory alignment signal possibly being delivered by a (pre)motor command pathway are discussed.
A limiting-diluiion system was established to measure the frequency of alloreactive cytotoxic T-l... more A limiting-diluiion system was established to measure the frequency of alloreactive cytotoxic T-lymphocyte precursors(CTL-p) in human poripherii! bl<K>dTcells. Culture medium supplemenicd with recombinant interleukin-2 enabled elonal expansion of all CTL-p sumulatcd by aUogeneic peripheral blood or spleen cells. The range of CTL-p frequencies in fully HLAmismaieheci responiier-stimulatnr combinatiotis was 1;24() to 1:1230. Splil-well analysis of individual niicrowclls showed that the cytotoxic T-ccll clones generated under limiting-dilution conditions showed exquisite specificity for the stitnulating alloantigens. Alloreactive CTL-p were enriched in the <)KT4 T-cell subset. This limiting-dilution system was highly reproducible and cati thus be applied to investigate human eytoloxic T-eeM precursor frequencies in various tiiniailly relevant situations.
The influence of niridazole, an anti-helminthic drug, on cell-mediated immune responses was inves... more The influence of niridazole, an anti-helminthic drug, on cell-mediated immune responses was investigated. Allograft rejection in mice as well as the in vitro induction of cytotoxic T lymphocytes (CTL) against murine alloantigen were used as the test system. Repeated daily oral treatment of host mice with niridazole (100 mg/kg) prior to and during allotransplantation resulted in the postponement of graft rejection, inducing a transitory functional state of allograft tolerance. The time interval between the termination ofniridazole administration and onset ofgraft rejection was estimated to be 5-7 days.
In the model system used here, cross-linking of T-cell receptor structures (TCR) by antigenpresen... more In the model system used here, cross-linking of T-cell receptor structures (TCR) by antigenpresenting cells (APCs) is substituted by the use of anti-F23.1 anti-T-cell receptor monoclonal antibody immobilized on Sepharose beads. We show that CR cross-linking of resting murine CD8+ T cells seeded at low cell densities is insufficient to induce responsiveness to the growth-promoting effect of interleukin-2 (IL-2), i.e. fails to induce expression of functional IL-2 receptors. The macrophage cell-line product, IL-2 receptor-inducing factor (RIF), but not IL-1, IL-3, IL4 and interferongamma (IFN-y) functions efficiently as a co-stimulator. Once activated, growth of CD8+ T cells is driven entirely by IL-2. We conclude that two restriction points control the activation of resting CD8+ T cells. While cross-linking of TCR is essential as the first step, RIF is required as the competence factor to induce IL-2 responsiveness. We consider the possibility that the ability of APCs to produce RIF determines the immunogenicity of APCs towards antigen-reactive resting CD8+ T cells.
Colonization of the oropharynx with potentially pathogenic microorganisms (PPM) is a highly signi... more Colonization of the oropharynx with potentially pathogenic microorganisms (PPM) is a highly significant factor in the pathogenesis of bacterial pneumonia in intensive care patients. Via colonization of the oropharynx, bacteria pass into the tracheobronchial tree, where they can give rise to pneumonia after overcoming pulmonary resistance mechanisms. By a new, prophylactic antibiotic treatment schedule consisting in selective decontamination of the digestive tract (SDD) with locally applied nonabsorbable antibiotics, Stoutenbeek achieved drastic lowering of the colonization and infection rate in trauma patients. In the present study, we wanted to check whether this new prophylactic antibiotic schedule can be applied on a surgical intensive care ward in all patients with long-term ventilation, irrespective of the diagnosis, and whether it affords advantages over a conventional antibiotic schedule. MATERIALS AND METHODS. All patients on a surgical intensive care ward in whom it was expected that mechanical ventilation would be necessary for more than 4 days were included in the study. During the first 6 months 83 patients were investigated, in whom antibiotics were only administered when the presence of infection had been confirmed, in accordance with generally accepted guidelines (control group). In the second 6-month period, 82 patients were selectively decontaminated with 4 x 100 mg polymyxin E, 4 x 80 mg tobramycin and 4 x 500 mg amphotericin B, administered through the gastric tube and in an antimicrobial paste in the oropharynx (SDD group). The SDD schedule entailed systemic administration of cefotaxime in the first 3-4 days. RESULTS. In the control group, enterobacteria/Pseudomonas spp. were isolated significantly more frequently than in the SDD group (P less than 0.001): in the pharyngeal smear in up to 53%, in the tracheal secretion up to 36%, and in the rectal smear in up to 93% of the patients In the SDD group in the 1 week the frequency of gram-negative aerobic bacteria in the pharynx decreased from 33% to 5%, in the tracheal secretion from 23% to 14% and in the rectum from 86% to 52% (24% in the second week). However, the decrease in gram-negative microorganisms was accompanied by significant increase in the frequency of Staphylococcus epidermidis and enterococci. The SDD schedule proved to be effective with regard to the rate of infection. In the control group, 35 patients developed pneumonia (42%) as against 5 patients receiving SDD prophylaxis (6%). The duration of mechanical ventilation in the patients with pneumonia was 5 days longer than in patients without pneumonia.(ABSTRACT TRUNCATED AT 400 WORDS)
In this work we study the role of subsets of human T cells, detectable by the OKT series of monoc... more In this work we study the role of subsets of human T cells, detectable by the OKT series of monoclonal antibodies, in the production of and the response to the lymphokine interleukin-2 (11-2) during the course of an allogeneic cytotoxic T lymphocyte response in vitro. The results obtained establish that the 11-2 producer cells reside within the OKT4 positive T cell subset. Once produced, I1-2 mediates the clonal expansion of alloantigenactivated cytotoxic T killer cells which reside in the OKT8 positive T cell subset. 11-2 appears to have no mitogenic activity on the activated OKT4 positive T cells which produce the lymphokine. In order to release I1-2, the OKT4 positive T cell requires a stimulus, such as allogeneic cells or the lectin phytohaemagglutinin A (PHA). Macrophages are also required for I1-2 production, but the macrophage requirement can be bypassed by a soluble macrophage product as found in supernatants of lymphocyte cultures stimulated with lipopolysaccharide (LPS), the biological activity presumably representing Interleukin-1 (Il--).
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Papers by Hermann Wagner