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Biomedical subjects

H Wagner

Publications and source records attributed to H Wagner.

At least 433 records · Page 24Linked to original sources
PubMed1989

[Frequency of colonization and pneumonia and development of resistance in long-term ventilated intensive-care patients subjected to selective decontamination of the digestive tract].

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)

Adolescent↗
PubMed1989

[Structure function relations of immunologically relevant molecules: impact of gene technology].

To date progress in our understanding of cell-mediated immune responses appears breath-taking. This is, at least in part, due to the fact that immunological problems become increasingly analysed by methods provided by modern molecular biology. This fruitful interconnection led to an understanding of the mechanisms governing antigen recognition by T cells, the lymphokine mediated control of immune responses and successful attempts to utilize this knowledge in therapeutic protocols.

Adjuvants, Immunologic↗
PubMed1989

[A revision prosthesis for the hip joint].

Following loosening of total hip prostheses increasing bone resorption occurs around the prosthesis, which can lead to extensive bony defects. In this paper a revision prosthesis for the femur is presented, which is fixed in the distal marrow cavity without cement, bridging the damaged prosthesis bed and stabilizing the femur. Vigorous bony regeneration begins in the resorption defects, which makes good the loss of bone substance. The revision prosthesis described for the cup is also implanted without cement. It allows additional fixation with screws and also onlay grafting, so that even when the acetabulum is badly damaged it is possible to change the prosthesis to obtain a good functional result and also allow recovery of the bone.

Acetabulum↗
PubMed1988

Anti-asthmatic effects of onions. Alk(en)ylsulfinothioic acid alk(en)yl-esters inhibit histamine release, leukotriene and thromboxane biosynthesis in vitro and counteract PAF and allergen-induced bronchial obstruction in vivo.

Five alk(en)ylsulfinothioic acid alk(en)yl-esters isolated from onions and four synthetic thiosulfinates inhibited 5-lipoxygenase of porcine leucocytes, histamine release and leukotriene B4 and C4 biosynthesis of human polymorphonuclear leucocytes, thromboxane B2 biosynthesis by human platelets and allergen- and PAF-induced bronchial obstruction of guinea-pigs. The anti-asthmatic and anti-inflammatory effects of onions depend in part on the thiosulfinate moiety: (Formula: see text).

Allergens↗
PubMed1988

IL-4 bypasses the immune suppressive effect of cyclosporin A during the in vitro induction of murine cytotoxic T lymphocytes.

We have analyzed at the clonal level the effect of IL-4 on the immune suppressive action of cyclosporin A (CsA) during the in vitro primary activation of anti-MHC alloantigen-reactive murine CD8+ CTL. Although neither IL-4 nor IL-2 alone were able to overcome the CsA-mediated suppression, the addition of IL-4 in the presence of IL-2 restored in a dose-dependent manner the induction of cytolytic activity. On the other hand, CsA greatly impaired proliferative responses of alloantigen-reactive CD8 T cells, thereby operationally dissecting proliferative responsiveness from acquisition of cytolytic activity during primary activation of alloantigen-reactive CD8+ T cells. The existence of a CsA-resistant induction pathway for Ag-specific CD8+ T cell-mediated cytolytic activity may be of relevance for experimental and clinical organ transplantation.

Animals↗
PubMed1988

Quantitative assessment of interleukin-2-producing alloreactive human T cells by limiting dilution analysis.

A limiting dilution (LD) culture system was developed to estimate the frequency of IL-2 producing alloantigen-reactive human helper T lymphocytes (HTL). E rosette-purified T cells or cell sorter-separated CD4+ and CD8+ subsets were co-cultured under LD conditions with irradiated allogeneic Epstein-Barr virus-transformed lymphoblastoid cell lines (LCL) in the absence of additional growth factors. IL-2 in microculture supernatants was detected in a bioassay combined with rapid colorimetric visualization (cleavage of MTT). Under these conditions, one out of 250-800 E+, 180-280 CD4+, and 440-1000 CD8+ T cells produced IL-2 after a culture period of 3 days. This quantitative analysis of alloantigen-specific human HTL is complete within 4 days and thus provides a rapid method with potential applications in various clinical situations, e.g., transplantation medicine.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1988

High-dose irradiated splenic stimulator cells show no endogenous interleukin-2 production but stimulate clonally developing helper T cells to produce interleukin-2.

The effect of various physical or chemical treatments of splenic stimulator cells on their endogenous, mitogen-inducible IL-2 production and on their ability to induce IL-2 production in clonally developing helper T lymphocytes was investigated. While most methods (T cell depletion by monoclonal antibodies plus complement, glutaraldehyde fixation, heat inactivation and high-dose irradiation) effectively suppressed the endogenous IL-2 production of splenic stimulator cells, only T cell depletion and high-dose (6000-10,000 R) irradiation sustained their stimulatory capacity. High-dose irradiated stimulator cells induced high numbers of clonally developing helper T lymphocytes to secrete IL-2. Moreover, this induction was found to be antigen-specific. Hence, high-dose irradiation is a simple, rapid and reliable method for the treatment of stimulator cells, especially when large numbers of cultures are to be screened.

Animals↗
PubMed1988

Acute and long-term effects of low-density lipoprotein apheresis on the serum concentrations of vitamins E and A.

Serum alpha-tocopherol and retinol concentrations were followed in four heterozygous adults and one homozygous child with familial hypercholesterolemia being treated by regular low-density lipoprotein (LDL) apheresis. Approximately 50% of plasma alpha-tocopherol was eliminated during a single apheresis procedure in the heterozygous adults, while a complete elimination of this vitamin along with LDLs was observed in the homozygous child. Absolute losses of alpha-tocopherol amounted to 13.4-22.5 mg/apheresis and are equivalent to the recommended dietary intake for 1.5 to 2 days. Despite these losses, no changes were observed either in serum alpha-tocopherol levels or in the ratio of alpha-tocopherol/total serum lipids after 12 months regular apheresis treatment. Serum retinol concentrations only showed a small decrease on apheresis, there being apparently no specific elimination of this vitamin. The absolute losses ranged from 42-422 micrograms/apheresis and were, therefore, much lower than the recommended dietary intake of the equivalent of 1500 micrograms retinol/day. It is concluded that no extra supplementation of these vitamins is required during LDL-apheresis therapy, although it may be advisable to monitor vitamin E status in patients on long-term, intensive therapy.

Adult↗
PubMed1988

Primary activation of murine CD8 T cells via cross-linking of T3 cell surface structures: two signals regulate induction of interleukin 2 responsiveness.

In the model system used here to study the minimal signal requirements for the activation of murine resting CD8 T cells, cross-linking of T cell receptor structures by antigen-presenting cells is substituted for by the use of anti-CD3 monoclonal antibodies immobilized in Sepharose beads. We show that cross-linking of CD3 structures, even in combination with CD8 structures, is necessary but insufficient to induce responsiveness to the growth-promoting effect of interleukin 2 (IL2), i.e. fails to induce expression of functional IL2 receptors. A macrophage cell line product termed IL2 receptor-inducing factor (RIF), but not IL1, IL3, IL4 or tumor necrosis factor, efficiently functions as costimulator. Once activated, growth of CD8 T cells is entirely driven by IL2. We conclude that two restriction points control the activation of resting CD8 T cells. While cross-linking of CD3 structures is essential as a first step, RIF is required as competence factor to induce IL2 responsiveness. We consider the possibility that the ability of antigen-presenting cells to produce RIF determines the immunogenicity of presented antigen towards antigen-reactive resting CD8 T cells.

Animals↗
PubMed1988

Reactivity of Ly-2+ T cells against 2,4,6-trinitrophenyl (TNP)-modified syngeneic stimulator cells: specificity, frequency of interleukin 2-producing Ly-2+ helper T cells and clonal segregation from Ly-2+ cytotoxic T lymphocytes.

The in vitro reactivity of purified murine Ly-2+ and L3T4+ T cells towards 2,4,6-trinitrophenyl (TNP)-modified syngeneic stimulator cells was analyzed. Both T cell subpopulations autonomously proliferated and produced interleukin 2. In either the Ly-2+ or L3T4+ T cell subset the frequencies of TNP-specific interleukin 2 (IL 2)-producing T lymphocyte precursors (IL 2 TL-p) were equally high (f = 1/400-1/1000). Clonally developing IL 2 TL of either T cell subset showed an exquisite antigen (TNP) specificity as shown by the split culture approach. TNP-specific Ly-2+ IL-2 TL used class I MHC (H-2Kk) gene products as major histocompatibility complex (MHC) restriction elements, while L3T4+ IL 2 TL proved to be class II MHC (H-2I-AkI-Ek) restricted. Clonal segregation analyses revealed that the majority of clonally developing TNP-reactive Ly-2+ TL segregated into either IL 2 TL-p or cytotoxic T lymphocyte presursors, i.e. both functions appear to be mutually exclusive. Less than 10% of the responding Ly-2+ T cells seemed to be bifunctional. These findings provide compelling evidence for the L3T4+ T cell-independent, autonomous reactivity of Ly-2+ T cells in MHC-restricted antigen-specific responses and suggest T-T cell interactions within the functional heterogenous Ly-2+ T cell population.

Animals↗
PubMed1988

Interleukin 4 (BSF-1) induces growth in resting murine CD8 T cells triggered via cross-linking of T3 cell surface structures.

To analyze the role of interleukin 4 (IL4, BSF-1) during primary activation of resting (high-density) murine CD8 T cells, a model system was used which bypasses antigen-presenting cells by the use of anti-T3 monoclonal antibodies immobilized on Sepharose beads. In high, but not in low cell density cultures, IL4 alone induced cell growth. In low cell density cultures, further to T3 cross-linking a soluble macrophage product was required as co-stimulator to induce sensitivity to IL4. This co-stimulator activity was unrelated to recombinant (r)IL1, rIL6 and rTNF-alpha (tumor necrosis factor alpha). In primary CD8 T cell responses rIL4-driven growth was about half of that induced by rIL2, and not inhibitable by anti-IL2 receptor antibodies. Higher concentrations of IL4 down-regulated cell proliferation. In the course of IL4-driven growth, the proliferating cells acquired sensitivity to the growth-promoting effect of IL2. Activated CD4 or CD8 T cells were found to be equally sensitive to the IL4 and IL2-driven growth pathway. Taken together, these results define a physiologic role of IL4 as growth factor during primary activation of resting CD8 T cells and thus extend the spectrum of target cells for IL4.

Animals↗
PubMed1988

L3T4+ T-cell-independent reactivity of Lyt2+ T cells in vivo.

The aim of this study was to analyze in vivo the L3T4+ T-cell-subset-independent reactivity of Lyt2+ T cells toward transplantation alloantigens. To this end, we depleted normal mice of L3T4+ T cells by injection of monoclonal antibodies to the L3T4 antigen. This procedure not only led phenotypically to a disappearance of L3T4+ T cells, but also effectively abolished reactivity toward class II MHC antigens in vitro and in vivo. However, L3T4+ T-cell-depleted mice still reacted to class I MHC alloantigens in vivo: after immunization with class I MHC alloantigens Il-2 receptor-bearing T cells appeared in the draining lymph nodes, and developed antigen-specific cytolytic activity. Moreover, upon in vivo priming the frequencies of class I MHC-specific precursors of Il-2-producing and cytolytic Lyt2+ T lymphocytes increased up to 20-fold. L3T4+ T-cell-depleted mice rejected class I MHC-bearing skin grafts promptly. We conclude that not only in vitro but also in vivo Lyt2+ T cells remain reactive toward class I MHC antigens in the absence of L3T4+ T helper cells.

Animals↗
PubMed1988

Concentration and purification of plant pathogenic viruses by field step electrophoresis.

Concentration and purification of plant pathogenic viruses by field step electrophoresis comprises a new and rapid preparative method with high throughput and short separation time. With this technique and combinations of field step and zone electrophoresis it is possible to purify plant pathogenic viruses from several contaminants in one separation step. Another application of field step electrophoresis allows the separation of viruses from each other.

Electrophoresis↗
PubMed1988

Cross-linking of T-cell receptors is insufficient to induce IL-2 responsiveness (activation) in resting Lyt-2+ T cells. IL-4 or RIF are essential as second signal.

High-density (resting) murine Lyt-2+ T cells exposed in vitro to the ligand concanavalin A (Con A), or immobilized F23.1 monoclonal antibody (mAb) recognizing an allotypic determinant on the T-cell receptor (TCR), or high-density (resting) allogeneic B stimulator cells remain IL-2-unresponsive; such cells do not express functional IL-2 receptors unless reconstituted with accessory cells. We conclude that cross-linking of TCR is insufficient as signal to induce IL-2 responsiveness, that is, activation. Both the macrophage product RIF and the T-cell product interleukin-4 efficiently induce the IL-2 responsiveness in resting Lyt-2+ T cells exposed in vitro either to the ligand Con A, or to immobilized F23 mAb, or to nonimmunogenic allogeneic stimulator cells. We conclude that two restricting points control the induction of IL-2 responsiveness (activation) in antigen-driven Lyt-2+ T-cell responses, that is, cross-linking of TCR by way of presented antigen and "costimulator" activity expressed by accessory cells. Both RIF and IL-4 express costimulator activity, therefore replacing the requirement for accessory cells.

Animals↗
PubMed1988

[IgG subclass deficiency in childhood. Changes in the antigen specific immune response and significance of low IgG4 level].

The definition of IgG subclass deficiency and the correlations between low IgG subclass serum concentrations and high incidence of infections in certain patients are still obscure. Therefore 260 children from 6 months to 18 years with severe recurrent infections or a known immunodeficiency were screened for IgG subclass deficiency. Nine patients with severe IgG2 deficiency (Ig2 less than 0.3 g/l) and 35 patients with non-detectable IgG4 in immunoprecipitation were detected. One of these patients had a concomitant IgA deficiency, eight revealed an additional IgA and IgG2 deficiency, two an IgA, IgG2, and IgG3 deficiency, eighteen an IgG2 deficiency and one patient an IgG2 and IgG3 deficiency. The proportion of patients with non-detectable IgG4 in immunoprecipitation was 13.5% and thus in the same order of magnitude as described in the literature for healthy people. Our data show that there is no relation between low IgG4 serum levels and the increased occurrence of severe infections. In all patients investigated with non-detectable IgG4 in immunoprecipitation the gene for the heavy chain gene constant domain C gamma 4 could be detected by Southern blotting. Using a sensitive ELISA method IgG4 could be directly demonstrated in all patients at a serum level of 0.5-29 micrograms/ml. Specific IgG4 antibodies against protein antigens could not be detected in IgG4-deficient patients. Nevertheless total IgG antibodies against diphtheria and tetanus toxoid reached protecting titers. Patients with IgG2 deficiency showed an impaired immune response against polysaccharides from pneumococci and haemophilus influenzae type b.

Adolescent↗