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Biomedical subjects

K Wonigeit

Publications and source records attributed to K Wonigeit.

At least 181 records · Page 10Linked to original sources

Exogenous IL2 partially reverts CML non-reactivity acquired during prophylactic immunosuppression with cyclosporin A of human allograft recipients.

Proliferative and cytolytic lymphocyte responses and the influence of exogenous interleukin 2 (IL2) on cell-mediated lympholysis (CML) reactivity were evaluated in 12 allograft recipients. Responses were induced by mitogenic lectins or by donor and third-party cells. Patients were tested immediately before transplantation (Tx) and one and three months after grafting. Prophylactic immunosuppression consisted of Cyclosporin A (CyA) and low-dose prednisone (P). Analysis of post transplant cells revealed a reduced overall proliferative T cell responsiveness induced by both alloantigens and mitogenic lectins. No evidence for donor-specific reduction of MLC responses was seen. Overall CML reactivity of post-Tx lymphocytes was also impaired. This was accompanied by donor-specific CML non-reactivity in six of seven patients with quiescent grafts. In these patients, the cytolytic potential against donor cells could be restored when maximal T cell help via exogenous IL2 was provided.

Adult↗

Cyclosporin A in pediatric kidney transplantation and its effect on posttransplantation growth.

Results of cyclosporin A (CyA) treatment following kidney transplantation in 28 children were compared with those of conventional immunosuppression with azathioprine (Aza) in 34 children. CyA was given in combination with low-dose prednisolone. Under CyA the 2-year survival rate of patients and grafts was 96%, under Aza the 2-year survival rate of patients was 94% and of grafts 68% (p less than 0.01). Graft function was slightly lower in the CyA than in the Aza group. Growth after kidney transplantation was evaluated in those patients with a first graft and a function of longer than 1 year. Annual growth velocity for bone age was normal or even accelerated in all children treated with CyA and significantly better than in the children treated with Aza. It is concluded that CyA treatment combined with low-dose prednisolone yields excellent results and allows normal growth rates after kidney transplantation.

Adolescent↗

Detection of polymorphic rat MHC antigen determinants in cryostat sections. A method for selecting monoclonal alloantibodies.

An immunohistological method for detection of rat MHC antigens by unconjugated primary alloantibodies is described. The procedure is based on secondary reagents specific for an allotypic marker of rat kappa light chains and makes possible differentiation between specifically bound alloantibody and the ubiquitously distributed interstitial immunoglobulin in the section. This technique can be used to pre-select monoclonal antibodies to be coupled to biotin or enzymes for histological application.

Animals↗

Influence of cyclosporine A on adaptive hypertrophy after unilateral nephrectomy in the rat.

The functional challenge to a transplanted kidney is comparable to that of a single kidney after unilateral nephrectomy. The single kidney model was used in rats to study the influence of the immunosuppressant CyA. Using this model interference with immunological or preservation/transplantation problems can be excluded. Two month old rats were studied 4 weeks after unilateral nephrectomy. After unilateral nephrectomy the juvenile rats had been fed for 28 days with 10 or 15 mg/kg BW CyA daily. These rats were compared to intact control rats and to age-matched uni-nephrectomized rats. Single kidney weight was measured in one group. Single kidney function was measured in a second group, first in the metabolic cage and then in experiments with isolated kidneys perfused under standard conditions. The glomerular filtration coefficient Kf was measured by micropuncture techniques. Glomerular capillary surface area was estimated after perfusion fixation in order to calculate the effective hydraulic permeability k of the glomerular capillary wall (k = Kf/S). Standard allogeneic skin transplantation across the MHC barrier was used to establish that the CyA dosage used was immunosuppressive. The results showed that the single kidney mass (as a measure of tubular hypertrophy) and GFR were suppressed under the influence of CyA compared to controls. Analysis of glomerular filtration parameters in the isolated perfused kidneys on the single nephron level had the following results: a small increase of the glomerular capillary surface (morphometry) was suppressed under CyA, whereas the effective hydraulic permeability (k) increased by almost 40% whether CyA was given or not.

Adaptation, Physiological↗

Developments in liver transplantation.

Liver transplantation has gained increasing interest. While liver grafting for tumor is successful over prolonged periods only in its early course, liver grafting for end-stage cirrhosis may lead to a long survival. Liver grafting in children is the most successful indication; in adults the results depend largely on timing and indication. Actual developments are mainly seen in the following points: a. Improvement in immunosuppression by use of Cyclosporin A. The resorption and metabolism of the drug, in relation to liver function, have to be carefully observed. b. The tendency to perform liver grafting electively instead of in emergency. c. Improvement in operative management, particularly the use of veno-venous bypass. d. The best possible anaesthesiological and intensive care management for the patients. It can be expected, that these developments will enable continuous improvement of results, particularly in an elective situation. One hundred and forty liver grafts have been done in our institution and the results are discussed herein. Progress in liver transplantation is marked by steadily growing numbers of liver grafts performed, and of centers performing grafts, as well as by improved success rates and the recommendation of the U.S. National Institutes of Health, based on discussions at a liver transplantation consent meeting, held in June 1983. This interest is also reflected in discussions among the medical and non-medical community. The first section of this paper will deal with the present state and results of liver grafting particularly, at our own institution and some actual developments in this field will be discussed.

Bile Ducts↗

Altered distribution of class I and class II MHC antigens during acute pancreas allograft rejection in the rat.

The expression of MHC class I and class II antigens was investigated in a model of acute pancreas allograft rejection in the rat. Pancreaticoduodenal and duct-ligated DA(RT1a)-to-LEW(RT1(1] and LEW(RT1(1]-to-LEW.1U(RT1u) pancreas grafts were compared with normal organs and with LEW(RT1(1] isografts at daily intervals from day 1 to day 10 after transplantation. The results show profound changes of MHC antigen distribution in allografts during the process of rejection. Exocrine acinar cells, being class-I-antigen-negative in the normal pancreas, strongly express these antigens during rejection. Class II antigens, normally not found in pancreatic endothelia or parenchymal cells, appear in duct epithelia, acinar cells, and endothelia of big vessels. Endocrine islet cells and smooth muscle cells stay Ia-negative throughout the rejection process. Focal class I reactivity is also observed in acinar cells of pancreaticoduodenal isografts; but class II antigens are neither seen in parenchymal cells nor in endothelia of any isograft. Thus, in the rat pancreas allograft model, the induction of class II antigens is an early phenomenon characteristic of an ongoing immune response, and it provides a valuable new diagnostic criterion. Antibodies reactive exclusively with donor-haplotype antigens demonstrate an increase in donor-derived class I and class II antigen-positive interstitial cells in addition to parenchymal antigenic changes. A possible effect of the antigenic alteration described on the course of the rejection process is discussed.

Animals↗

Effect of Borna disease virus infection on athymic rats.

Homozygous athymic nude rats (rnu/rnu) infected intracerebrally with Borna disease virus produced relatively high titres of infectious virus in the central nervous system. However, no clinical signs of disease or pathological alterations could be found during a 100 day observation period. In contrast, heterozygous euthymic albino littermates (rnu/+), which were used as controls, reacted in a similar manner to immunocompetent Lewis rats. They developed behavioural alterations which coincided with encephalitis and retinitis. The results obtained confirm our previous concept that the genesis of Borna disease, at least in rats, is attributed to a cellular immune response.

Animals↗

Analysis of the rat major histocompatibility system by Southern blot hybridization.

The organization of the rat major histocompatibility complex, RT1, was studied at the DNA level by Southern blot hybridization. Genomic DNA from eight different RT1 congenic rat strains was digested by various restriction enzymes and was hybridized under stringent conditions with probes of mouse class I and class II H-2 genes. Few cross-hybridizing DNA fragments, showing no polymorphism, were seen with class II A alpha and A beta probes. The class I probes allowed for the distinction of about 8 to 19 cross-hybridizing bands, which exhibited extensive polymorphism. With the use of five RT1 recombinants, about 20% of the DNA fragments could be mapped to the RT1.A region, which codes for the ubiquitously expressed class I antigens, and about 80% to the RT1.C region-determining class I-like antigens, which are different from RT1.A antigens with respect to tissue distribution, restriction function in immune responses, and allograft rejection. The number of class I genes present in the rat genome and the possible relationship of RT1.C to H-2Qa, Tla of the mouse are discussed.

Animals↗

[Heart transplantation in cardiomyopathy].

Within the spectrum of presently accepted candidates for heart transplantation, end-stage heart failure in dilated cardiomyopathy has become the principle indication. Although several indicators of poor prognosis have been specified, the decision for heart transplantation is primarily made on clinical grounds. Expected long-term survival after transplantation is 60 to 80% at one year and more than 50% at five years. Since July, 1983, 50 patients underwent orthotopic heart transplantation, 38 of whom had been suffering from dilated cardiomyopathy. Ages ranged from nine to 54 years with a mean of 40 years. At present, 38 patients are alive, 34 are discharged from hospital, 14 have returned to work or school. Physical capacity and cardiac function are normal. There was no difference between the cardiomyopathy patients and the coronary artery disease patients with respect to rate and severity of rejection episodes, infection and long-term findings. Heart transplantation is considered a promising routine treatment for end-stage heart failure in particular in younger patients with dilated cardiomyopathy.

Adolescent↗