Cyclosporin A (CsA) prevents the generation of mature thymic alpha/beta T cells but spares gamma/delta T lymphocytes.
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Animals↗
Biomedical subjects
H Wagner
Publications and source records attributed to H Wagner.
Analysis of primary T cell responses to intact and fractionated microbial pathogens.
Freshly isolated human T lymphocytes were tested for their response to mycobacteria, mycobacterial lysates, 2 dimensional (2D) PAGE separated mycobacterial lysates, leishmania and defined leishmanial antigen preparations. While gamma delta T cells proliferated vigorously in the presence of mycobacteria and mycobacteria derived lysates, a significant stimulation from 2 D gel separated lysates was not detected. In addition gamma delta T cells failed to respond towards leishmania or leishmanial components. In the alpha beta T cell compartment some donors, presumably according to their state of immunity against mycobacteria, responded to mycobacteria, mycobacterial lysates and 2 D gel separated mycobacterial lysates. Neither freshly isolated gamma delta T cells nor alpha beta T cells from naive donors did mount a significant immune response against leishmania.
Animals↗
A temporal window for lateralization of interaural time difference by barn owls.
Lateralization of interaural time difference by barn owls (Tyto alba) was studied in a dichotic masking experiment. Sound bursts consisted of two parts: binaurally time-shifted noise, termed the probe, was inserted between masking noise. The owls indicated that they detected and lateralized the time-shift in the probe by a head turn in the direction predicted from sign of the time-shift. The general characteristics of head turns in response to this stimulus was similar to the head turns elicited by free-field stimulation or to head turns in response to presentation of the probe alone. The owls could easily lateralize stimuli containing long probes. The number of correct turns decreased as probe duration decreased, demonstrating that the masking noise interfered with the owls' ability to lateralize the probe. The minimal probe duration that the animals could lateralize ("minimal duration") became shorter as burst duration decreased. Minimal duration ranged from 1 ms to 15 ms for the two subjects and burst durations from 10 to 100 ms. These findings suggested that owls possess a temporal window. A fitting procedure proposed by Moore et al. (1988) was used to determine the shape of the temporal window. The fitting procedure showed that the shape of the owls' binaural temporal window could be described by the same algorithms as the human monaural temporal window. Thus, the temporal window is composed of a short time constant that determines the central part of the window, and a longer time constant that determines the shape at the skirts of the window.
Acoustic Stimulation↗
Application of purified polysaccharides from cell cultures of the plant Echinacea purpurea to mice mediates protection against systemic infections with Listeria monocytogenes and Candida albicans.
Purified polysaccharides from cell cultures of the plant Echinacea purpurea were investigated for their ability to enhance phagocytes' activities regarding nonspecific immunity in vitro and in vivo. Macrophages (M phi) from different organ origin could be activated to produce IL-1, TNF alpha and IL-6, to produce elevated amounts of reactive oxygen intermediates and to inhibit growth of Candida albicans in vitro. Furthermore, in vivo the substances could induce increased proliferation of phagocytes in spleen and bone marrow and migration of granulocytes to the peripheral blood. These effects indeed resulted in excellent protection of mice against the consequences of lethal infections with one predominantly M phi dependent and one predominantly granulocyte dependent pathogen, Listeria monocytogenes and C. albicans, respectively. Specific immune responses to sheep red blood cells (antibody production) and to listeria (DTH) were not affected by the polysaccharides. The possibility of clinical use is discussed.
Animals↗
Application of purified polysaccharides from cell cultures of the plant Echinacea purpurea to test subjects mediates activation of the phagocyte system.
Polysaccharides purified from large-scale cell cultures of the plant Echinacea purpurea were tested for their ability to activate human phagocytes in vitro and in vivo. These substances enhanced the spontaneous motility of PMN under soft agar and increased the ability of these cells to kill staphylococci. Monocytes were activated to secrete TNF-alpha, IL-6 and IL-1 whereas class II expression was unaffected. Intravenous application of the polysaccharides to test subjects immediately induced a fall in the number of PMN in the peripheral blood, indicating activation of adherence to endothelial cells. This fall was followed by a leukocytosis due to an increase in the number of PMN and a lesser increase of monocytes. The appearance of stab cells and some juvenile forms and even myelocytes indicated the migration of cells from the bone marrow into the peripheral blood. The acute phase C-reactive protein (CRP) was induced, probably due to activation of monocytes and macrophages to produce IL-6. In addition a moderate acceleration of the erythrocyte sedimentation rate was observed. Altogether, as in mice, the polysaccharides could induce acute phase reactions and activation of phagocytes in humans. The possibility of clinical use is discussed.
Adjuvants, Immunologic↗
Steroid profiles of brown adipose tissue.
In brown adipose tissue of alp-marmot (Marmota marmota), badger (Meles meles) and Wistar rats steroids of C21- and C19-type are identified and quantified. The detection of 3 alpha-hydroxy-5 alpha-pregnan-20-one, 3 alpha-hydroxy-5 beta-pregnan-20-one, 3 alpha,21-dihydroxy-5 alpha-pregnan-20-one, 3 alpha,21-dihydroxy-5 beta-pregnan-20-one and 3 beta,21-dihydroxy-5 alpha-pregnan-20-one is of special interest since sleep-inducing properties have been described with these steroids.
Adipose Tissue, Brown↗
Immunologically active polysaccharides of Arnica montana cell cultures.
From the nutrition medium of Arnica montana cell cultures two homogeneous polysaccharides, an acidic arabino-3,6-galactan-protein with mean Mr of 100,000 and a neutral fucogalactoxyloglucan with mean Mr of 22,500 have been isolated by DEAE-Sepharose CL-6B and Sephacryl S-400 column chromatography. Their structures were elucidated mainly by methylation analysis, partial acidic and enzymatic hydrolysis and 13C NMR spectroscopy. The fucogalactoxyloglucan shows a pronounced enhancement of phagocytosis in vivo. The arabino-3,6-galactan-protein displays a strong anticomplementary effect and stimulates macrophages to excrete the tumour necrosis factor (TNF alpha).
Carbohydrate Sequence↗
Crosslinked staphylococcal enterotoxin B stimulates CD8+ T cells only in the presence of unlinked costimulator signals.
The superantigen staphylococcal enterotoxin B (SEB) binds to class II MHC expressing cells and subsequently causes selective activation of T cells carrying appropriate T cell receptor (TCR) V beta chains. Apparently SEB acts as a bifunctional molecule by bridging class II MHC structures with the appropriate TCR-V beta chains. This assumption predicts that immobilized SEB ought to stimulate purified, class II MHC negative murine T cells. We show here that immobilized SEB lacks the ability to trigger murine CD8 T cells. Responsiveness obtained at a high T cell concentration is due to contaminating class II MHC-positive lymphocytes. Complementation of the culture system with syngeneic irradiated B cells blasts effectively restores responsiveness. The proliferating cells exhibit SEB specific cytotoxicity and a bias for V beta 8 expression. Since no evidence for leakiness of SEB covalently bound to sephadex beads was obtained, the data imply that immobilized SEB in fact binds to the TCR of T cells expressing the appropriate V beta chains. However, for primary activation additional costimulatory signals are required which can be provided in an unlinked fashion by activated B cells. Resting B cells are activated by immobilized SEB to cells expressing high costimulator activity. As such, the data point out a third function of SEB.
Animals↗
Murine CD4+ and CD8+ T cells are activated by the superantigen (SA) staphylococcal enterotoxin B (SEB) and exhibit MHC-unrestricted cytotoxicity.
Resting CD8+ and CD4+ murine T cells become efficiently activated by the superantigen (SA) staphylococcal enterotoxin B (SEB). Limiting dilution experiments reveal that roughly every third CD8+ or CD4+ T cell could be induced to proliferate. Surprisingly, besides CD8+ T cells, also CD4+ cells acquire a high cytolytic activity upon activation with SEB. Both subpopulations only lyse MHC class II positive target cells in the presence of SEB. However the recognition of SEB by CTL is independent of the haplotype of the MHC, i.e. is MHC-unrestricted. In addition the recognition of SEB is independent of the coreceptor molecules CD4 and CD8, respectively.
Animals↗
Flavonoids from the Aboveground Parts of Ruscus aculeatus.
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Journal Article↗
A new method for the in vitro screening of inhibitors of angiotensin-converting enzyme (ACE), using the chromophore- and fluorophore-labelled substrate, dansyltriglycine.
In our search for antihypertensive plant constituents, we developed a new in vitro assay for the detection of angiotensin-converting enzyme inhibitors in plant extracts. The chromophore- and fluorophore-labelled tripeptide dansyltriglycine is used as substrate, which is cleaved by the enzyme into dansylglycine and diglycine. The product dansylglycine and unreacted substrate are separated and quantified by reversed phase high performance liquid chromatography with UV detection. This target-directed enzyme assay is very specific, highly sensitive and reproducible, and lends itself very easily to automation.
Amino Acid Sequence↗
Isolation and Identification of Homologues of Ajoene and Alliin from Bulb-Extracts of Allium ursinum.
From the chloroform extract of ALLIUM URSINUM L. (Liliaceae) bulbs, in addition to other sulfur-containing constituents ( E/Z)-4,5,9-trithiadeca-1,6,11-dien-9-oxide [= methylajoene) and ( E/Z)-4,5,9-trithiaocta-1,6-dien-9-oxide (= dimethylajoene) were isolated and identified by NMR and mass spectroscopy. These two compounds were also found in A. SATIVUM but in lower amounts. The higher contents of the corresponding precursors (+)- S-methyl- L-cysteine sulfoxide (MCSO) and methylallyl/allylmethy] thiosulfmate in A. URSINUM water/methanol extracts correspond with the higher amounts of ajoene homologues.
Journal Article↗
Transcortical aphasia. Importance of the nonspeech dominant hemisphere in language repetition.
While a relative preservation of repetition in acute transcortical aphasia (TA) has usually been associated with the functional integrity of the speech dominant (left) perisylvian area, recent amytal data (Bando et al., 1986) have suggested a fundamental role of the nondominant (right) hemisphere in language repetition. The neuroradiological correlates of repetition were studied in a consecutive series of 21 patients with acute TA. A similar frequency of either perisylvian or extraperisylvian pathology was found. In 2 patients with perisylvian pathology, the injection of amytal in the hemisphere contralateral to the lesion abolished repetition. Positron emission tomography (PET) in another patient revealed marked hypometabolism over the entire left cortical mantle ipsilateral to a basal ganglia lesion, suggesting that preserved repetition was carried out by right hemisphere structures. This was confirmed in a second patient with left extraperisylvian pathology, in whom a second lesion in the right hemisphere resulted in impaired repetition. These findings suggest that the spared contralateral hemisphere may subserve residual repetition in some transcortical aphasic patients with a lesion within or outside the speech-dominant perisylvian area.
Aged↗
A novel form of CD4 (L3T4) mRNA in the murine fetal liver results in cell-surface expression of the L3T4 antigen.
The expression of the L3T4 antigen during ontogeny in the murine fetal liver has been investigated in parallel by northern blot analysis and cytofluorometry. The L3T4 gene is transcribed in the murine fetal liver in two polyadenylated mRNA species with the size of 3.5 kb and 3.7 kb. Whereas the 3.5-kb mRNA is expressed from days 13 to 18 of gestation, expression of the 3.7-kb mRNA is found only from days 16 to 18 of gestation and thus appears to be developmentally regulated. Immunofluorescent staining of fractionated fetal liver cells from days 12 to 18 of gestation with the anti-L3T4 antibody (GK1.5) provides evidence that cell-surface expression of the L3T4 antigen on a subset of lympho-haematopoietic cells in the murine fetal liver is the product of a novel form of L3T4 mRNA with the size of 3.5 kb.
Animals↗
Oral administration of idarubicin as first line cytostatic therapy in patients with metastasized breast cancer and favourable prognosis. A trial of the phase II study group of the Association for Medical Oncology of the German Cancer Society.
Idarubicin is a new anthracycline derivative with therapeutic efficacy in metastatic breast cancer. In a phase II trial we treated 23 patients with advanced breast carcinoma and favourable prognostic factors. Oral dose of idarubicin was 15 mg/m2 day 1-3 repeated every 3 weeks. All patients were pretreated with hormones. Idarubicin was administered as first line chemotherapy. 20 patients were evaluable for response: 3 patients achieved partial remission, 12 patients stable disease; tumour progression occurred in 5 patients. 3 patients were not evaluable for response because only 1 treatment cycle was administered. Main toxicites were leukopenia (median WHO-grade: 2,r:0-4), nausea and vomiting (median: 1,r:0-4) and alopezia (median: 1,r:0-3). 1 patient died in septic shock: Immediately after the administration of one idarubicine cycle, she was extensively irradiated because of bone metastasis. The fatal course of the disease in this patient does not depend only on the idarubicin therapy, but also on the extensive bone infiltration and on intensive radiation therapy. Idarubicin proved to be an effective drug in metastatic breast cancer with low systemic toxicity and the advantage of oral administration. The drug is an enrichment of therapeutic armament, especially in patients with soft tissue and bone metastasis.
Administration, Oral↗
New antiasthmatic drugs from traditional medicine?
Several plants are used in traditional medicine for the treatment of bronchial asthma. We are trying to identify the active compound(s) and their mode of action. For the isolation and identification of the active principles, different chromatographic methods, HPLC, MPLC, elementary analysis, UV, mass, 1H- and 13C-NMR spectroscopy are used. Whole plant extracts, fractionated extracts and pure compounds are tested in the following pharmacological systems: cyclooxygenase and lipoxygenase pathway of arachidonic acid metabolism, bronchial obstruction of guinea pigs after inhalation of allergens, platelet-activating factor (PAF), histamine or acetylcholine, PAF-induced bronchial hyperreactivity of guinea pigs, histamine release, chemoluminescence and chemotaxis of human polymorphonuclear leukocytes as well as thromboxane biosynthesis of human platelets. As active compounds in onion extracts, thiosulfinates and cepaenes could be identified. They exert a wide spectrum of pharmacologic activities, both in vitro and in vivo. Tetragalloyl quinic acid from Galphimia glauca, suppressed allergen- and PAF-induced bronchial obstruction, PAF-induced bronchial hyperreactivity (5 mg/kg orally) in vivo and thromboxane biosynthesis in vitro. Hitherto unknown alkaloids from Adhatoda vasica showed pronounced protection against allergen-induced bronchial obstruction in guinea pigs (10 mg/ml aerosol). Androsin from Picrorhiza kurroa prevented allergen- and PAF-induced bronchial obstruction (10 mg/kg orally; 0.5 mg inhalative). Histamine release in vitro was inhibited by other compounds of the plant extract yet to be identified. Pharmacological effects of plant extracts and pure compounds in man are under investigation.
Allium↗
Antiasthmatic effects of Picrorhiza kurroa: androsin prevents allergen- and PAF-induced bronchial obstruction in guinea pigs.
In the Ayurvedic medicine, Picrorhiza kurroa Royle ex Benth. is used for the treatment of liver and lung diseases. Using different chemical and pharmacological methods, we could identify the phenol glycoside androsin as active compound preventing allergen and platelet-activating factor induced bronchial obstruction in guinea pigs in vivo (10 mg/kg p.o.; 1 h prior to the inhalation challenge). Histamine release from human polymorphonuclear leukocytes in vitro was inhibited by other compounds yet to be identified.
Acetates↗