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Biomedical subjects

R Engemann

Publications and source records attributed to R Engemann.

At least 37 records · Page 2Linked to original sources

Rejection prophylaxis with interleukin-2 receptor antibody BT 563: mechanisms of action on human cells.

We investigated the in vitro immunosuppressive effect of BT 563, a monoclonal antibody, against the alpha-chain of the human interleukin-2 (IL-2) receptor (p 55), which has been used to prevent transplant rejection in several clinical trials. We also measured the proliferative T cell alloresponse and pCTL frequencies of BT563-treated kidney transplant patients. In mixed lymphocyte cultures BT 563 caused a reduction of T cell proliferation to about 50%. This could not be reversed by the addition of exogenous IL-2. A more effective reduction (80%) was seen in the generation of cytotoxic T cells from CML cultures and at the clonal level. The specific T cell response after preincubation with antigen and BT 563 was not reduced so that BT 563 did not induce tolerance. The in vitro findings indicated that BT 563 had a significant but incomplete immunosuppressive effect. This correlated with the clinical course and ex vivo analysis of PBL from BT 563-treated patients after kidney transplantation.

Antibodies, Monoclonal↗

Temporal patterns of immunoblot-reactive antibodies to cytomegalovirus in transplant recipients.

A total of 234 sera from 44 allograft recipients were compared with 12 sera from 9 immunocompetent patients with symptomatic cytomegalovirus (CMV) infection and with 20 sera of 20 healthy individuals with latent CMV infection. The presence of immunoreactive proteins was not associated with a specific transplant group or with different immunosuppressive regimens but rather with the kinetics of the immune response. Acute phase sera demonstrated early antibodies to proteins p38 and p48, followed by high or still rising antibodies to high molecular weight proteins, particularly p150, and their later decline to persistent lower levels. Convalescent phase sera were identified serologically by the transient appearance of IgG antibodies directed to 22-26 kDa polypeptides. Immunoreactive p44 was present in 85% of all patients with mild disease and in 40% of all patients with severe CMV disease. When tested in parallel, the immunoblot analysis was shown to be a more sensitive indicator of early CMV antibodies in allograft recipients than the ELISA technique.

Antibodies, Viral↗

The role of T suppressor cells in the maintenance of spontaneously accepted orthotopic rat liver allografts.

Orthotopic liver allografts from BN donors to LEW recipients are spontaneously accepted, and the recipients develop donor-specific immunological unresponsiveness. This unresponsiveness may be mediated by suppressor T cells. Immunomagnetically purified splenic T cells from LEW rats bearing BN liver grafts were shown to adoptively transfer suppression of skin, heart, and kidney graft rejection in a donor-specific manner, prolonging the survival of BN but not third-party DA grafts. However, the suppressor T cells were sessile, being resident in the spleen but not present in thoracic duct lymph. The presence of a nonrecirculating suppressor T cell in rats spontaneously accepting liver transplants is strongly suggestive of an important function in the maintenance of donor-specific unresponsiveness, although the contribution of other possible mechanisms of unresponsiveness has not been investigated.

Animals↗

Influences of Ginkgo biloba on cyclosporin A induced lipid peroxidation in human liver microsomes in comparison to vitamin E, glutathione and N-acetylcysteine.

The in vitro effect of cyclosporin A (CsA) on lipid peroxidation in human liver microsomes was investigated, and efforts were made to prevent the resulting toxic effect of CsA. Microsomes were prepared from human liver resection material and incubated with CsA (0, 10, 30, 100, 300, 1000 micrograms/mL) for one hour (pH 7.4, 37 degrees, 95% O2, 5% CO2). Subsequently the resulting concentrations of malondialdehyde equivalents (MDA) were determined, a breakdown product of lipid peroxidation. Furthermore the duration of incubation was varied (0, 15, 30, 60, 90 min) using a CsA concentration of 300 micrograms/mL. CsA was shown to stimulate MDA-formation to up to 10-fold of the control value in both a time and concentration dependent manner. The dosage dependent experiment stated above was repeated, adding alpha-tocopherol (vitamin E, 1 mM), reduced glutathione (GSH, 1 mM), N-acetylcysteine (0.1, 0.3, 1, 3 mM), and Ginkgo biloba extract (Gbe, 15, 50, 150 micrograms/mL), respectively, to the medium of incubation. Vitamin E, a potent radical scavenger, proved to inhibit lipid peroxidation almost totally. Both GSH and N-acetylcysteine were also able to prevent lipid peroxidation, suggesting that the antioxidant effect of GSH might be caused by its thiol group and does not depend on the integrity of the whole molecule. Gbe inhibited CsA induced lipid peroxidation in a concentration dependent manner. This effect of Gbe was diminished yet not totally abolished when FeCl3 was added to the medium of incubation, whereas N-acetylcysteine even slightly enhanced CsA stimulated lipid peroxidation in the presence of iron. These results suggest that Gbe might be able to prevent radical mediated damage to human membranes caused by CsA.

Acetylcysteine↗

Cyclosporin-A-induced lipid peroxidation in human liver microsomes and its influence on cytochrome P-450.

The present in vitro study using human liver tissue was performed to investigate the effect of cyclosporin A on lipid peroxidation and cytochrome P-450 concentration in isolated liver microsomes. Incubations were either carried out with cyclosporin A concentrations of 10, 30, 100 and 300 micrograms ml-1 for 1 h or for different time periods (15, 30, 60 and 90 min) with cyclosporin A 300 micrograms ml-1. Lipid peroxidation was monitored measuring the amount of malondialdehyde. In additional experiments the effect of reduced and oxidized glutathione (1 mM) on cyclosporin-A-induced lipid peroxidation in human liver microsomes was studied. Cyclosporin A caused a significant dose and time-dependent increase of the lipid peroxidation product malondialdehyde. At the highest cyclosporin A concentration (300 micrograms ml-1) malondialdehyde production increased 5-fold in comparison to corresponding control values. Incubations for different time periods resulted in a 5-fold net increase of malondialdehyde formation after 90 min. In the presence of reduced glutathione, cyclosporin-A-induced lipid peroxidation was significantly inhibited. Furthermore, cyclosporin-A-induced microsomal lipid peroxidation was accompanied by a significant dose-dependent decline of the microsomal cytochrome P-450 content. At a cyclosporin A concentration of 300 micrograms ml-1, cytochrome P-450 content was decreased to 49% in comparison to control values. In the presence of reduced glutathione, cyclosporin A decreased the cytochrome P-450 concentration only to 79% (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclosporine↗

[Diagnostic imaging and treatment of an invasive thymoma together with myasthenia gravis].

A 40-year old woman with an invasive thymoma and myasthenia gravis is described in this article. Chest-x-ray, CT and MRI of the mediastinum could not offer definite results on tumour malignancy. Radical surgical removal was the consequence. This revealed a tumour infiltration of the pleura and pericardium; hence an adjuvant irradiation must have been performed. Mestinon--treatment was afterwards gradually reduced.

Adult↗

[In vivo 31-phosphorus magnetic resonance spectroscopy of liver diseases].

31P-MR spectroscopy was performed in 12 patients with focal and diffuse liver disease and in ten normal controls, using surface coils. Results so far show a significantly increased concentration of PME/beta-ATP and of PDE/beta-ATP in patients with liver metastases and in one patient with hepatic involvement by malignant lymphoma. The spectra of liver cirrhosis and fatty livers showed no characteristic changes.

Adult↗

Monitoring of renal allografts by duplex ultrasound.

Deterioration of renal transplant function due to rejection is accompanied by changes in renal blood flow that can be measured by duplex ultrasound (DU). In the present study, 60 transplanted patients were followed up. A total of 233 duplex examinations, 68 percutaneous biopsies, 44 renal scintigraphies, and 6 transplant nephrectomies were performed on these patients. Diagnoses were made on the basis of clinical and histological data. Renal perfusion was calculated by means of DU. In addition, the arterial Doppler signals were quantified using a pulsatility index (PI). Mean perfusion of normal renal allografts was 0.47 l/min. A decrease in blood flow could be found in acute vascular and chronic rejection but not in acute cellular rejection. A lack of renal perfusion due to acute vascular rejection was observed in four patients. Mean PI, used as a parameter of DU, rose significantly in all forms of rejection, which could be diagnosed with a sensitivity of 93% and a specificity of 86%. Cyclosporin overdosage did not alter the Doppler flow shape.

Cyclosporins↗

[First successful clinical small intestine transplantation. Tactics and surgical technic].

A case of successful clinical small bowel transplantation is demonstrated. A segment of 60 cm of jejunum and ileum has been harvested from the sister of the recipient and has been brought in heterotopic position in the first operative step. It was anastomosed to the recipient's GI-tract 6 weeks later. This procedure has the advantage that the graft can recover from ischemic damage in heterotopic position and that an immunological steady state can be achieved. This case of successful clinical small bowel transplantation offers a new causal therapy for patients with short gut syndrome.

Adult↗