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Biomedical subjects

K Wonigeit

Publications and source records attributed to K Wonigeit.

At least 127 records · Page 7Linked to original sources
PubMed1990

Single dose pharmacokinetics of ciclosporin and its main metabolites after oral ciclosporin as oily solution or capsule.

The commercially available oily solution of ciclosporin which has to be suspended before intake is disliked by some patients for bad taste and has a variable bioavailability. In this investigation the oral pharmacokinetics of ciclosporin and its main metabolites 1 and 17 of the oily solution (Sandimmun) and a soft gelatine capsule preparation of ciclosporin were compared in a crossover fashion in 10 kidney allograft recipients. The results demonstrate a bioequivalence of both formulations. In either case metabolite 17 had a significantly longer half-life than either ciclosporin or metabolite 1. At earlier time-points the concentration of ciclosporin could be best correlated with metabolite 1 and at later time-points with metabolite 17. Both metabolites were less correlated with each other in the late absorption phase of ciclosporin.

Adult↗
PubMed1989

T cell activation by monoclonal antibodies directed to different epitopes on the human T cell receptor/CD3 complex: evidence for two different modes of activation.

The mouse monoclonal antibody (mAb) BMA031 (IgG2b) has recently been described to be directed against a monomorphic part of the human T cell receptor (TcR) alpha/beta. In vitro analysis of its stimulatory potential for mononuclear cells revealed two patterns of responsiveness. Out of 35 tested individuals only 2 generated a proliferative response to low antibody concentrations (15 ng/ml; "high responders"), the others ("low responders") responded only to high antibody concentrations (1.5 micrograms/ml); the anti-CD3 mAb UCHT1 (IgG2b) stimulated only the two high responders. This response pattern to BMA031 was determined by the accessory cell compartment in the culture. Stimulation by BMA031 in low responders demonstrated some unusual features: (a) high antibody concentrations were required, (b) addition of autologous serum had no inhibitory effect and (c) vigorous depletion of macrophages reduced but did not abolish the proliferative response. These characteristics were shared by two other mAb, BMA032 and BW239/347, presumably directed against the TcR alpha/beta but not by several other antibodies to the TcR/CD3 complex. Thus, the results demonstrate unusual stimulatory properties of three anti-TcR alpha/beta mAb, inducing a proliferative response without antibody cross-linking. This suggests that the stimulatory effect of anti-TcR/CD3 complex mAb is not only determined by their isotype, but also strongly depends on their epitope specificity.

Antibodies, Monoclonal↗
PubMed1989

T cell differentiation in athymic nude rats (rnu/rnu): demonstration of a distorted T cell subset structure by flow cytometry analysis.

The expression of T cell-associated antigens was analyzed on extrathymically differentiated T cells from athymic nude (rnu/rnu) rats. Two-color flow cytometry and monoclonal antibodies were used to compare the subset structure of the rnu/rnu T cell population with that of normal T cells. In adult nude rats CD4+ and CD8+ cells were found which co-expressed the OX19 antigen (CD5) clearly defining them as T cells. Double-positive (CD4+CD8+) cells were not detected in nylon wool-enriched rnu/rnu T cells. The ratio of CD4+ to CD8+ cells in nude rat lymph node cells did not significantly differ from normal T cells. However, the composition of the nude rat CD4+ and CD8+ subsets [as identified by the subset-dividing monoclonal antibodies OX22 and P4/16 (anti-RT6)] differed from that found in control rats. The most striking observation among the rnu/rnu CD4+ subset was an inversion in the ratio of OX22+ to OX22- cells (0.5) compared to normal rats (2.3). Only 61% of the nude rat CD4+ cells were found to be RT6+ compared to 85% of rnu/+ CD4+ cells. In the rnu/rnu CD8 subset the proportion of RT6 co-expressing cells was also markedly reduced (38% vs. 77% of the CD8+ subset). Furthermore, the nude rat CD8+ subset contained a substantial number of OX22- cells which were nearly absent in normal rats. The demonstration of cells bearing T cell markers in adult athymic rats further confirms the existence of an extrathymic pathway of T cell differentiation. The unusual T cell subset composition found in athymic rats, however, indicates that T cell subset generation and/or maintenance along this pathway differs from normal T cell development.

Animals↗
PubMed1989

Cholera toxin modulates the T cell antigen receptor/CD3 complex but not the CD2 molecule and inhibits signaling via both receptor structures in the human T cell lymphoma Jurkat.

The human T cell lymphoma Jurkat can be activated by stimuli directed either against the T cell antigen receptor-CD3 antigen complex (TcR/CD3) or the CD2 molecule. Stimulation of cells via the TcR/CD3-complex or via the CD2 molecule increases inositol phosphates and cytoplasmic free calcium. Pretreatment of Jurkat cells with cholera toxin leads to a decrease of TcR/CD3 expression on the surface of the cells, while the expression of CD2 is unaffected. In contrast to this distinct effect on the receptor expression, signaling via both pathways is inhibited by cholera toxin. The most convincing explanation for the cholera toxin-mediated inhibition of signaling is that cholera toxin interrupts the signaling pathways at a point where both, stimulation via TcR/CD3 and via CD2, use the same route. The earliest common point of the two signaling pathways, at least in the Jurkat cell line, seems to be the CD3 complex because after its down-regulation (and functional inactivation) both pathways of activation are interrupted.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

A mutant rat major histocompatibility haplotype showing a large deletion of class I sequences.

The LEW. 1LM1 inbred rat strain, which has been derived from a (LEW x LEW.1W) F2 hybrid, carries a major histocompatibility (RT1) haplotype which is distinct from that of the LEW strain (RT1(1)) in that certain RT1.C region-determined class I antigens are not expressed. Here we show that this phenotypic defect is due to genomic deletion of about 100 kb of the RT1.C region. Certain deleted DNA fragments have been cloned from the wild-type DNA into the EMBL4 vector. Five clones have been characterized and are shown to possess different restriction maps and to each carry a single stretch of class I cross-hybridizing sequences. Probes derived from the non-class I coding part of two clones detect fragments which are present in the wild-type but absent from the lm1 mutant. The type of deletion described here in the rat is discussed in the context of H-2D/Q deletions in the mouse.

Animals↗
PubMed1989

[Detection of cyclosporin A in breast milk--is breast feeding contraindicated?].

Cyclosporin A (CyA) was measured simultaneous in breast milk and maternal and fetal blood with a new monoclonal specific radioimmunoassay in a patient who was treated with Cyclosporin A during pregnancy because of kidney transplantation. CyA-levels in breast milk were 15 to 90% higher than in maternal blood. In case of breast feeding a child would take up less than 5 percent of an immunosuppressive dose. However, we would recommend ablactation because of the toxicity and the unknown side effects of CyA for the child's immunologic system.

Adult↗
PubMed1989

Cellular mechanisms of rejection and regeneration in peripheral nerve allografts.

A model of rejection and regeneration of peripheral nerve allografts in rats is presented. A 2.5-cm segment of 28 right sciatic nerves was transplanted orthotopically from LEW.1W to DA and from DA to LEW.1W. With a microsurgical technique, proximal and distal coaptations were performed. In an autologous control group the same surgical procedure was applied. Evaluation included clinical estimation of motor recovery and macroscopic appearance of the graft, electrophysiological examination, conventional histology, and immunohistology. The latter concentrated on demonstration of monomorphic and polymorphic determinants of MHC class I and II antigens and of macrophages. By functional, electrophysiological, and histological parameters it was demonstrated that after rejection a certain degree of regeneration took place in the allografts. Both rejection and subsequent regeneration were studied in detail by immunohistology. During the course of Wallerian degeneration MHC class I expression on myelin sheaths could be demonstrated. When the rejection response occurred, additional MHC class II expression on myelin sheaths and on vascular endothelial was observed. Recipient specific class I-positive macrophages were infiltrating the graft from the epineurium and the coaptation sites, and were later present at the sites of myelin degradation. At 6 weeks postoperatively donor-specific MHC products were no longer detectable, but recipient-specific Schwann cells were present in the allograft tissue. We conclude that a rejection response renders a peripheral nerve allograft acellular but does not destroy the nerve architecture, still enabling it to function as an axon conduit. The regeneration in the rejected allograft however lacks the positive neurotropic and -trophic influence physiologically provided by viable Schwann cells.

Animals↗
PubMed1989

Urinary excretion of ciclosporin and 17 of its metabolites in renal allograft recipients.

Renal elimination of the immunosuppressant ciclosporin is virtually unknown. Therefore, in 17 renal allograft recipients under steady-state conditions we studied the urinary excretion of ciclosporin and 17 of its metabolites in blood and 24-hour urine. Patients with liver dysfunction or treated with drugs potentially influencing the metabolism and elimination of ciclosporin were excluded from the study. Ciclosporin and its metabolites were measured by HPLC. Metabolite but not ciclosporin excretion was strongly correlated with creatinine clearance. Metabolites 18 and 26 (beta, epsilon-cyclic metabolite) were rarely found in blood but were excreted in considerable amounts in urine. Approximately 3% of the administered dose of ciclosporin per day undergoes renal elimination in unchanged form or as metabolites investigated. The data suggest glomerular filtration of ciclosporin metabolites, a difference in the rate of elimination between ciclosporin and the metabolites and some kind of metabolism or active transport mechanism for metabolites in the kidney.

Adolescent↗