Search PubMed⌕ Search

Biomedical subjects

K Wonigeit

Publications and source records attributed to K Wonigeit.

At least 109 records · Page 6Linked to original sources
PubMed1990

Genetically determined lack of CD45R- T cells in healthy individuals. Evidence for a regulatory polymorphism of CD45R antigen expression.

A genetic polymorphism of CD45R expression was identified resulting in a lack of CD45R- lymphocytes in approximately 8% of healthy individuals. Family studies revealed an autosomal dominant mode of inheritance of the variant CD45R expression pattern. PBMC from donors possessing the variant type did not lose the CD45R antigen after in vitro activation, whereas a decrease of CD45R molecules was readily detected in individuals with the normal pattern. The expression of CD45RO antigens, as well as memory cell function, did not differ between both groups. These data show that activation and in vivo priming of T cells is not necessarily associated with a loss of CD45R antigen expression.

Antibodies, Monoclonal↗
PubMed1990

The course of untreated acute rejection and effect of repeated anti-CD3 monoclonal antibody treatment in rhesus monkey liver transplantation.

The effect of single and repeated treatment of liver allograft rejection using an anti-CD3 monoclonal antibody (FN18) was studied in a rhesus monkey model. Eight RhLA-mismatched monkeys received initial postoperative immunosuppression with CsA/prednisolone for 28 days. After cessation, acute rejection occurred in all animals (days 28-50). Control animals (n = 3) receiving no rejection treatment developed a chronic progressive rejection and died at days 112-160. In the animals treated with FN18 (n = 5), the first acute rejection was successfully reversed. T lymphocytes were cleared from the peripheral blood and the graft. Increased class I and class II MHC-antigens on hepatocytes were reduced to normal levels within 5 days of treatment. The second rejection treatment remained ineffective in two animals with antiidiotypic antibodies to FN18 but was successful in two animals with a low antimouse response. These four animals survived 160-509 days. The results have a number of implications regarding the course of untreated rejection in human liver transplant recipients and repetitive rejection treatment with monoclonal antibodies.

Animals↗
PubMed1990

Different activation states of human lymphocytes after antibody-mediated stimulation via CD3 and the alpha/beta T-cell receptor.

BMA031 is an IgG2b antibody directed towards the human alpha/beta T-cell receptor that is able to induce proliferation of peripheral blood mononuclear cells independent of antibody crosslinking. The proliferative response to BMA031 during the first 3 days of culture is usually of similar magnitude to that induced by the IgG2a CD3 antibody OKT3 but decreases quickly afterwards. Stimulation by BMA031 induces no measurable IL-2 release, very low expression of the IL-2 receptor, and does not trigger cytotoxic effector function. However, cross-linking of the antibody or addition of IL-2 leads to enhanced and prolonged proliferation, strong IL-2 receptor expression, and cytotoxic activity, features that are usually found after stimulation by the IgG2a CD3 antibody OKT3 in soluble form. The stimulatory effect of BMA031 cannot be diminished by IL-2 receptor blocking, whereas stimulation by OKT3 is strongly reduced. Moreover, proliferation induced by BMA031 has lower sensitivity to inhibition by ciclosporin than OKT3. From these results two major conclusions can be drawn: (1) an IL-2-independent way of activation may be important for the short-term proliferation of the T cells stimulated by BMA031 and (2) after stimulation by BMA031, cells reach a state of activation that is different from that induced by OKT3. These differences are most likely related to the different specificities of the antibodies, alpha/beta TcR versus CD3, suggesting that different activation signals are triggered via CD3 and via the alpha/beta TcR.

Antibodies, Monoclonal↗
PubMed1990

Strain differences in sensitivity of rats to Mycoplasma arthritidis ISR 1 infection are under multiple gene control.

At least 5 female rats from each of 24 inbred (ACI, AS, BDIX, BH, BN, BS, BUF, DA, LE, LEW, MWF, OM, SPRD-Cu3, W-Krypt, and WKY), RT1 congenic [BH.1L(LEW), LEW.1A(AVN), LEW.1C(WIST), LEW.1LV3(BH), LEW.1K(SHR), and LEW.1N(BN)], and F1 hybrid [(LEW x BN)F1, (LEW.1W x LEW.1A)F1, and (LEW x LEW.1W)F1] strains, representing eight independent major histocompatibility complex (MHC) haplotypes (a, b, c, dv1, k, l, n, and u) and five related RT1 haplotypes (av1, lv1, lv3, uv2, and uv3), were inoculated intravenously with Mycoplasma arthritidis, and the severity of the polyarthritis that developed was determined by estimating arthritis scores and weight reductions. The 24 inbred, congenic, and F1 hybrid rat strains differed considerably in their sensitivity to infection with M. arthritidis and in the severity of the polyarthritis that they developed. Statistical evaluation showed that in the acute phase (days 1 to 42 after infection) as well as in the chronic phase (days 39 to 121 after infection) of the disease, the means of the arthritis scores for the strains form a continuous variation without significant interruptions, with the very sensitive LEW rats, the RT1 congenic rats on LEW background, the F1 hybrids with LEW, and the MWF, BS, BH, and DA rats on one end and the resistant WKY, BUF, W-Krypt, LE, and OM rats on the other end. A continuous variation was also observed for the means of the growth rates. There were, however, no significant differences between the sensitive and the resistant rat strains in the antibody titers determined by complement fixation test and enzyme immunoassay. Heritabilities of arthritis scores were calculated for all strains (h2 = 0.39 to 0.62), for the RT1 congenic strains (h2 = 0.04 to 0.14), and for several strains with identical MHC genes (h2 = 0.61 to 0.93). The results show that non-MHC genes are probably responsible for the sensitivity of rats to infection with M. arthritidis.

Acute Disease↗
PubMed1990

Influence of ciclosporin on epidermal proliferation after mechanical skin irritation.

In mice (NMRI and hr/hr), ciclosporin, subcutaneously administered once daily over 7-10 days, influenced epidermal hyperproliferation induced by abrasion of superficial epidermal layers. While in vehicle-treated control animals the mechanical irritation of skin caused an increase in 3H-thymidine triphosphate incorporation rate into DNA and also in epidermal thickness of tail and flank skin, the hyperproliferative response was diminished in ciclosporin-treated animals. Thus, only a slight increase of the 3H-thymidine triphosphate incorporation rate and of epidermal thickness was measured after pretreatment with ciclosporin, the effect being dose-dependent. The strongest inhibitory activity was found after application of 30 mg/kg BW. These findings indicate that the immunosuppressive peptide ciclosporin inhibits the epidermal proliferation in vivo.

Animals↗
PubMed1990

Cyclosporine monitoring in liver allograft recipients: two distinct patterns of blood level derangement associated with nephrotoxicity.

The parallel measurement of specific and nonspecific CyA levels by second generation radioimmunoassays based on monoclonal antibodies proved to be an effective procedure to monitor both parent CyA levels and the capacity to eliminate its metabolite. Using this monitoring procedure it could be shown that CyA-associated nephrotoxicity in the early course after liver transplantation is associated with two distinct patterns of blood level derangement. One pattern is characterized by increased parent drug levels, the other by an increased metabolite concentration resulting from severely disturbed CyA metabolite excretion. This raises the possibility that not only the parent drug but also some of its metabolites may exert nephrotoxic effects when present in excessively high concentrations. This finding provided the rationale for a therapeutic CyA-monitoring regimen taking into account both specific and nonspecific measurements. In liver transplant patients monitored according to this regimen and treated with quadruple immunosuppression the incidence and severity of CyA-associated nephrotoxicity was markedly reduced. The metabolite-associated type of nephrotoxicity was only found in patients with severely disturbed liver function.

Creatinine↗