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Biomedical subjects

H Wagner

Publications and source records attributed to H Wagner.

At least 451 records · Page 25Linked to original sources
PubMed1988

Wedelolactone and coumestan derivatives as new antihepatotoxic and antiphlogistic principles.

For the study of structure-activity relationships, the antihepatotoxic wedelolactone (7-methoxy-5,11,12-trihydroxy-coumestan) and 6 coumestan derivatives were synthesized by the application of a modified method of Wanzlich. An evaluation of the biological characteristics of the synthetic compounds and acuminatin from Musa acuminata showed that most of the wedelolactone derivatives significantly protected primary cultured liver cells from the toxicity of CCl4, galactosamine (Galc), and phalloidin, and strongly inhibited the activity of 5-lipoxygenase in porcine leukocytes. The hepatocyte protective activity was dependent on the C-7 substitution with pharmacological efficacy decreasing in the following order: EtO greater than MeO greater than OH greater than CH3(CH2)9. In addition, a free OH at C-5 of the wedelolactone molecule was shown to be important in protecting hepatocytes from CCl4 and Galc damage. Similar observation regarding the effect of C-7 substitution in wedelolactone was obtained in the 5-lipoxygenase test. In general, an increase in the lipophilicity in ring A increased the inhibition of 5-lipoxygenase activity. The synthetic wedelolactone was also found to have stimulatory effect on the RNA synthesis in isolated nuclei from hepatocytes.

Alanine Transaminase↗
PubMed1988

Two distinct signals regulate induction of IL-2 responsiveness in CD8+ murine T cells.

In the model system used here, cross-linking of T-cell receptor structures (TCR) by antigen-presenting 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, IL-4 and interferon-gamma (IFN-gamma) 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.

Animals↗
PubMed1988

In vitro stimulation of human granulocytes and lymphocytes by pico- and femtogram quantities of cytostatic agents.

The influence of a broad concentration range of naturally occurring naphthoquinones and other cytotoxic or cytostatic agents (azathioprine, colchicine, cyclophosphamide, fluorouracil, methotrexate and vincristine) on human granulocytes and lymphocytes was investigated in a systematic in vitro study. At high concentrations (100 micrograms-10 ng/ml) nearly all substances showed the known cytotoxic or immunosuppressive effects, whereas most of the same compounds displayed immunostimulating activities at very low concentrations (10 ng-10 fg/ml). After a cold shock or heat treatment lymphocytes became more sensitive against these compounds in the active concentration range than untreated cells. These results possibly give an explanation for the antitumour activity of some plant extracts, for which a direct cytotoxicity due to the applied low dose can be excluded.

Antineoplastic Agents↗
PubMed1988

[Immunologic in vivo and in vitro studies on Echinacea extracts].

Ethanolic extracts of Echinacea purpurea, E. pallida and E. angustifolia roots were examined for immunological activity in the carbon clearance test with mice and in the granulocyte test. In the in vivo experiment all extracts, administered orally, were found to enhance phagocytosis significantly. These results correlate with the stimulation of phagocytosis in the in vitro granulocyte test. The lipophilic fractions of the extracts appeared to be more active than the polar fractions. All extracts were analyzed by HPLC in order to correlate the chemical constituents with the immunological activities.

Animals↗
PubMed1988

A method for the biocybernetic physiological investigation of postural motor control and its disorders in children.

On a biocybernetic basis, a method for the investigation of human postural motor control with optimal multifrequent binary test-signals is described. The examinations presented demonstrate that a comprehensive and quantitative characterization of normal postural motor control and its disorders is possible by means of this method in children. The examination time is short, the motor task used is simple, and the load is physiologically adequate and standardized.

Child↗
PubMed1987

Frequency of herpes simplex virus-specific murine cytotoxic T lymphocyte precursors in mitogen- and antigen-driven primary in vitro T cell responses.

The aim of this study was to assess and to compare the frequencies and specificities of herpes simplex virus (HSV)-specific cytotoxic T lymphocyte precursors (CTL-p) in mitogen (concanavalin A)-activated splenic T cells, as well as in antigen-activated splenic T cells of normal nonimmunized mice. In the mitogen-driven system one of 130 T cell blasts developed clonal progenies able to lyse specifically HSV-infected syngeneic targets. In the antigen-driven system HSV-specific CTL-p could be detected in normal lymphocytes provided the stimulator cells used were enriched for dendritic cells and pulsed with high concentrations of heat-inactivated HSV. Depending on the mouse strain used, the frequencies of HSV-specific CTL-p ranged from 1/500 to 1/10,000 in normal mice. Upon antigen priming within local lymph node cells, an increase of frequencies from 1/500 to 1/170 was observed in CBA/Ca mice.

Animals↗
PubMed1987

Methylation of the enhancer region of avian sarcoma virus long terminal repeat suppresses transcription.

The effect of methylation of an enhancer on transcription was studied. A 245 bp enhancer-containing a fragment of the LTR of the avian sarcoma virus was methylated in vitro and ligated back into a vector which lacked the upstream enhancer sequence. The transient expression in QT6 cells indicated that methylation of the enhancer-containing sequence severely reduced the extent of transcription.

Avian Sarcoma Viruses↗
PubMed1987

Frequency analysis of class I MHC-reactive Lyt-2+ and class II MHC-reactive L3T4+ IL 2-secreting T lymphocytes.

The reactivity of Lyt-2+ or L3T4+ T cells stimulated with either mutant class I or class II MHC alloantigens was studied. Whereas stimulation with class I MHC antigens induced only Lyt-2+ T cells to proliferate and to secrete IL 2, stimulation with class II MHC alloantigens induced L3T4+ but not Lyt-2+ T cells. When the frequencies of precursors of IL 2-secreting T lymphocytes (IL 2TL-p) were determined by limiting dilution analyses, class I MHC-reactive Lyt-2+ T cells displayed frequencies (f = 1/200) as high in magnitude as those within class II MHC-reactive L3T4+ (f = 1/100). Clonally developing IL 2TL of either T cell subset were antigen-specific, as shown in split-culture experiments. Whereas L3T4+ helper TL could be induced to specific IL 2 secretion over a long time period (days 3 to 9), Lyt-2+ TL showed a marked time optimal on day 4; thereafter, the number of TL colonies inducible to secrete IL 2 decreased steadily. IL 2 production and IL 2TL-p frequencies of unseparated T responder cells were not the numerical superposition of the two individual T cell subsets (Lyt-2+ + L3T4+); the latter finding is likely to reflect regulatory influences of Lyt-2+ T cells on IL 2-secreting L3T4+ T cells.

Animals↗
PubMed1987

Functional and biochemical characteristics of a murine interleukin 2 receptor-inducing factor.

High density (resting) murine Lyt-2+ T cells exposed in vitro to the ligand concanavalin A (Con A) remain interleukin 2 (IL 2) unresponsive, i.e. do not express functional IL 2 receptors, unless reconstituted with accessory cells. This finding provides a bio-assay to define functional and biochemical characteristics of an IL 2 receptor-inducing factor (RIF). RIF bioactivity as secreted from the macrophage cell line P388-D1 is associated with a trypsin-sensitive protein of 44 kDa which does not need to be glycosylated and which binds to and can be eluted from hydroxylapatite and phenyl-Sepharose. While both RIF and IL 1 are produced by accessory cells the lymphokines separate from each other according to functional and biochemical criteria. Either accessory cells, RIF or the protein kinase C activator phorbol myristate acetate can substitute for each other and are equally active for the induction of IL 2 responsiveness in high-density Lyt-2+ T cells exposed to Con A. To explain these results we conclude that in the mitogen system used, induction of IL 2 responsiveness (activation) represents a two-step event in which first cross-linking of cell surface structures by the ligand Con A excites the responder T cells, which subsequently respond to the accessory cell product RIF.

Animals↗
PubMed1987

Identification of interleukin 2-producing T helper cells within murine Lyt-2+ T lymphocytes: frequency, specificity and clonal segregation from Lyt-2+ precursors of cytotoxic T lymphocytes.

The prime aim of this study was to assess whether the autonomous primary mixed lymphocyte culture response of Lyt-2+ T cells towards class I major histocompatibility complex (MHC) antigens reflects in terms of interleukin 2 (IL2) production and cytotoxicity the activation of multifunctional Lyt-2+ T cells, or the activation of functionally distinct T cell subsets. The results demonstrate that highly purified Lyt-2+ T cells proliferate in response to class I MHC antigens, as opposed to L3T4+ T cells which react towards class II MHC antigens. In both responder cell types proliferative responses are associated with IL2 secretion, while only Lyt-2+ T cells develop measurable cytotoxic effector cells. The precursor frequency of IL2-producing helper cells in MHC class I-reactive Lyt-2+ T cells equals that in MHC class II-reactive L3T4+ T cells (f = 1/500-1/1000). In clonal segregation analysis greater than 90% of Lyt-2+ colonies secreting IL2 do not develop cytotoxic activity, while greater than 90% of Lyt-2+ cytotoxic T cells fail to produce detectable IL2. A minority of less than 10% of Lyt-2+ T cells appears to be bifunctional. As such the results point out the existence of functionally committed T cells within class I MHC-reactive Lyt-2+ T cells able to produce either IL2 or to develop into cytotoxic effector cells.

Animals↗
PubMed1987

Clonal activation of cytotoxic lymphocyte precursors by monoclonal anti-CD3 antibody: analysis of feeder cell requirements.

Activation of cytotoxic lymphocyte precursors (CLP) by the mitogenic monoclonal anti-CD3 antibody OKT3 was studied under limiting dilution (LD) culture conditions. One out of 2-6 E-rosette-purified T cells gave rise to a cytotoxic T cell (CTL) clone when cultured in the presence of OKT3 (0.2-2 ng/ml), recombinant IL-2 (100 U/ml), and irradiated feeder cells. Clonal CLP activation was optimally supported by a combination of E-rosette-depleted non-T feeder cells with small numbers of T cells added back. Among the cell lines tested, Fc-receptor-bearing monocytic cell lines U937 and HL-60 were efficient feeder cells whereas T cell lines (Jurkat, Molt-4, Ke37) did not support clonal CLP activation. These data indicate that clonal activation of CLP and differentiation into cytotoxic effector cells under LD culture conditions are critically influenced by the type and number of feeder cells used.

Antibodies, Monoclonal↗