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R J ten Berge

Publications and source records attributed to R J ten Berge.

At least 19 recordsLinked to original sources
PubMed2000

[Immunology in medical practice. XXX. Organ transplantation: indications and results].

During the past 30 years, solid organ transplantation has developed into a routine medical procedure. Currently, one-year transplant survival rates for kidney, heart, liver and pancreas are between 80 and 90%; for most organs, the long-term results are fair with 5-year survival rates of 60%. Inclusion criteria for potential recipients have become less stringent. These days, potential recipients are rarely excluded on the basis of their calendar age alone. The development of more and stronger immunosuppressive drugs has facilitated transplantation across wider immunological differences between donor and recipient with good results. While the number of patients on the waiting lists for organ transplantation increased, the number of organs offered for donation decreased. This has resulted in waiting times of several years for most organ transplantations. While the short-term outcome has improved significantly over the past decades, the long-term outcome has not. Most renal transplants, for example, are lost due to chronic rejection. The challenge for the future will be to improve the long-term outcome of organ transplantation and to decrease the morbidity associated with chronic immunosuppressive therapy.

Age Factors↗
PubMed1997

[Immunology in clinical practice. VI. Current immunosuppressive drugs].

Immunosuppressive drugs are agents capable of modulating at least one type of immune response in vivo at doses with tolerable side-effects. Classical immunosuppressive drugs include corticosteroids, azathioprine, cyclophosphamide, methotrexate and cyclosporine. In the past two years tacrolimus and mycophenolate mofetil were registered as immunosuppressive drugs. Tacrolimus interferes with the calcium-dependent signal transduction of T-lymphocytes. Mycophenolate mofetil is an inhibitor of purine synthesis by inhibition of the enzyme inosine monophosphate dehydrogenase. Both tacrolimus and mycophenolate mofetil have proven efficacy in both prevention and treatment of acute allograft rejection. The new drugs are stronger than the classical ones but do not cause more adverse reactions. The value in clinical medicine of some new, promising immunosuppressive drugs, i.e. sirolimus (rapamycin), mizoribine, brequinar and leflunomide remains to be proven.

Graft Rejection↗
PubMed1997

[Immunology in medical practice. I. Introduction].

Fundamental immunology has seen a tremendous development in the past decades. This has resulted in a large body of knowledge, part of which has led to applications in laboratory diagnosis, but of which little has made its way to the clinic in terms of new therapies. The progress in understanding pathogenesis of diseases is also slow. This journal is planning a series of articles that highlight the recent achievements of immunology and their consequences for understanding and treating disease.

Allergy and Immunology↗
PubMed1996

Comparison of T cell responses in patients with a long-term surviving renal allograft versus a long-term surviving liver allograft. It's a different world.

The aim of the present study was to analyze whether acquired transplantation tolerance had developed in patients with a long-term surviving renal or liver allograft. Analysis of antidonor cytotoxic T cell precursor frequencies was performed in 31 renal allograft recipients and 9 liver allograft recipients with good graft function 2 years after transplantation. The results demonstrated that, before transplantation, normal antidonor T cell responses were generated in both groups of patients. Two years after transplantation, donor-specific CTL nonresponsiveness had developed in a minority of the renal transplant recipients. In contrast, 8 out of 9 liver transplant recipients showed donor-specific mixed lymphocyte culture and CTL nonresponsiveness. These findings indicate that development of donor-specific T cell nonresponsiveness is not a common event after kidney transplantation, whereas liver transplantation seems to induce, at least in vitro, a state of donor-specific T cell nonresponsiveness.

Cytotoxicity, Immunologic↗
PubMed1996

Increased dermal expression of ICAM-1 and VCAM-1 after administration of OKT3 in man.

OKT3 induces a systemic release of cytokines and a profound peripheral lymphocytopenia. In vitro, tumor necrosis factor-alpha, interleukin-1, and interferon-gamma increase adhesion molecule expression on vascular endothelium. To investigate the effects of OKT3 induced cytokine release on endothelial- and lymphocyte adhesion molecule expression in vivo, we studied sequential skin biopsies of six renal allograft recipients treated for acute rejection with 5 mg OKT3. An additional group of six patients treated for acute rejection with 50 mg methylprednisolone served as a control group. Compared to pre-treatment biopsies, biopsies taken 4.5- and 24 hours after the first OKT3 dose showed a maximal increase in VCAM-1 and ICAM-1 expression, respectively. In parallel, an increased number of CD2+, CD11a+, and CD49d+ mononuclear cells in the skin was observed in all OKT3 treated patients. No changes were observed after methylprednisolone treatment. We conclude that the OKT3 induced cytokine release induces increased ICAM-1- and VCAM-1 expression on vascular endothelium, leading to increased influx of CD2+ lymphocytes which may contribute to the peripheral lymphocytopenia after OKT3.

Acute Disease↗
PubMed1995

Biphasic granulocytopenia after administration of the first dose of OKT3.

The effects of the administration of OKT3, a second immunoglobulin G2a (IgG2a) anti-CD3 monoclonal antibody (mAb), and its isotype switch variant IgA on granulocyte kinetics were compared for 5 hours after the first administration of the mAb. In addition, in vivo and in vitro studies were performed on alterations in expression of CD11b and CD62L induced by these mAbs. Within 15 minutes after administration OKT3 and IgG2a anti-CD3 mAbs induced a significant decrease in circulating granulocytes, whereas IgA anti-CD3 mAb did not. Apparently the initial decrease in circulating granulocytes depends on the heavy chain of the administered anti-CD3 mAb, resulting in immunocytoadherence and sequestration in the lungs. Increased adherence to pulmonary endothelium by altered expression of CD11b and CD62L plays a minor role in this first granulocytopenia, because each mAb exerted the same effects on these adhesion molecules in vitro. The second decrease in granulocyte counts occurred 60 minutes after administration of each mAb and correlated with a significant increase in expression of CD11b and CD62L in vivo and with upregulation of CD11b and down-regulation of CD62L in vitro. These alterations could be related to the presence of tumor necrosis factor-alpha both in vivo and in vitro. Thus granulocyte kinetics from 30 minutes after administration of each anti-CD3 mAb resemble neutrophil kinetics induced by TNF-alpha.

Adult↗
PubMed1994

Sequestration of labelled granulocytes in the lungs following administration of OKT3 is dose-dependent.

In the present study the consequences of administration of low-dose (0.5 mg) OKT3 for respiratory side-effects and pulmonary sequestration of labelled granulocytes are compared with the known effects of 5 mg OKT3. Ten renal transplant patients were studied, of whom five were treated with 0.5 mg OKT3 and five with 5 mg OKT3. None of the patients in the 0.5 mg group and two of the patients in the 5 mg group experienced dyspnoea. Sequestration of labelled granulocytes in the lungs was significantly lower in the patients receiving 0.5 mg OKT3 compared with the patients receiving 5 mg OKT3. The simultaneously occurring peripheral blood granulocytopenia was significantly more severe in the 5 mg group than in the 0.5 mg group. We suppose that this sequestration of circulating granulocytes in the lungs is at least partly mediated by complement activation products. In vitro it is demonstrated that fixation of complement activation products on peripheral blood lymphocytes depends on the concentration of OKT3 present in the culture medium. We conclude that respiratory side-effects shortly following infusion of OKT3 are related to complement-induced pulmonary leucostasis, the degree of which is dependent on the administered dose of OKT3.

Acute Disease↗
PubMed1994

Low-dose OKT3 induction therapy following renal transplantation: a controlled study.

In a prospective clinical study we tested the immunosuppressive properties and toxicity of low-dose OKT3 induction therapy in renal transplant recipients. 50 consecutive renal transplant recipients were alternatingly assigned to low-dose OKT3 induction or prednisolone/cyclosporin. Low-dose OKT3 induction treatment consisted of 0.5 mg OKT3 twice daily for 10 days, initially combined with azathioprine and prednisolone maintenance immunosuppression that was converted to prednisolone/cyclosporin at the end of the course. During a 15-29-month follow-up period, low-dose OKT3 induction therapy was found to reduce significantly the incidence of acute rejections, as compared to the usual prednisolone/cyclosporin maintenance immunosuppression (21 versus 52%, P = 0.02). There also was a tendency towards an improved graft function after low-dose OKT3, although no significance was reached. Furthermore, compared to a historical control group of renal transplant patients in whom acute rejection was treated with 5 mg OKT3 daily, low-dose OKT3 appeared to cause fewer side-effects. We conclude that low-dose OKT3 induction therapy is superior to prednisolone/cyclosporin in preventing acute rejection after renal transplantation and that it is better tolerated than conventional OKT3 treatment.

Adult↗
PubMed1994

Increase of sTNF receptor levels in acute renal allograft rejection after treatment with OKT3.

The use of OKT3 is associated with severe clinical side-effects. Adverse reactions are partly attributed to release of tumour necrosis factor (TNF). TNF binds to two receptors on the outer membranes of most human cell lines. Shedding of these proteins (sTNFR-p55 and sTNFR-p75) may block biological effects of TNF. Here we show a fair correlation between serum levels of sTNFRs and renal function as measured by glomerular filtration rate (GFR). In addition we assessed levels of sTNFR-p55 and sTNFR-p75, corrected for reduced renal clearance, in renal allograft rejection and following treatment with OKT3. Corrected serum levels (CSL) of sTNFR-p55 and sTNFR-p75 were determined in 12 renal allograft patients treated for an acute rejection episode with either OKT3 or methylprednisolone (MPNS). Serum levels of CSLsTNFR-p55 and CSLsTNFR-p75 in both groups prior to anti-rejection treatment were not elevated. CSLsTNFRs peaked at 1 h after the administration of OKT3, whereas in the MPNS group CSLsTNFRs remained unchanged. We conclude that in acute renal transplant rejection CSLsTNFRs increase after treatment with OKT3. In spite of high circulating sTNFRs levels all OKT3-treated patients suffered from clinical side-effects.

Adult↗
PubMed1994

Immunosuppressive drugs in clinical medicine.

Immunosuppressive drugs are agents capable of suppressing the development of at least one type of immune response in vivo at doses with minimal side-effects. Some characteristics regarding the mechanism of action of corticosteroids, azathioprine, cyclophosphamide, cyclosporine and monoclonal antibodies anti-CD3 are reviewed. Corticosteroids induce a redistribution of lymphocytes and display an anti-inflammatory effect; the immunosuppressive effect of azathioprine seems to consist mainly of its suppression of the inflammatory response; cyclophosphamide and cyclosporine influence the immune system itself and anti-CD3 monoclonal antibodies suppress cellular immunity fairly specifically. Finally, a brief summary of their use in renal disease, systemic vasculitis and connective tissue diseases is given.

Clinical Medicine↗
PubMed1994

Interleukin-8 during peritonitis in patients treated with CAPD; an in-vivo model of acute inflammation.

CAPD-related peritonitis was used as an in-vivo model to study Il-8 during peritoneal inflammation. Eleven episodes were studied in nine patients, who were followed on 8 consecutive days from the start of peritonitis and once after recovery (control). Il-8 was measured in dialysate (night dwells) and serum. The Il-8 time course was compared to Il-6 and TNF alpha. In addition, an in-vivo relationship between dialysate Il-8 and intraperitoneal accumulation of neutrophils was studied. A highly increased peritoneal appearance rate of Il-8 was found in the acute phase that decreased to control values during recovery. A remarkable parallelism was observed for dialysate Il-8 and Il-6 with respect to the time course and the peritoneal appearance rate. In contrast, the appearance rate of TNF alpha was much less and had a different time course. In three of four cases where the dialysate Il-8 peak occurred on day 2, the dialysate Il-6 peak still coincided with Il-8, in contrast to TNF alpha (always day 1). Dialysate Il-8 generally exceeded serum concentrations during the entire follow-up, indicating intraperitoneal Il-8 synthesis. A positive correlation was present between the dialysate Il-8 peak and the maximal number of neutrophils in dialysate. This relationship was absent for Il-6 and TNF alpha. In five of six episodes where neutrophils were quantified on both day 1 and 2, the Il-8 peak occurred simultaneously with the neutrophil peak. These findings suggest that Il-8 is involved in the recruitment of neutrophils towards the dialysate during peritonitis.

Acute Disease↗
PubMed1993

Application of a monoclonal antibody against a neoepitope on activated C4 in an ELISA for the quantification of complement activation via the classical pathway.

In order to study the activation of the complement system via the classical pathway we have attempted to raise antibodies specific for C4 activation products. Of 20 mouse monoclonal antibodies (mAbs) obtained, one appeared to react with an activation dependent epitope exposed on the activation products C4b, C4bi, C4c (C4b/c) as well as on iC4, but not on native C4. Using this antibody as a capture antibody and polyclonal biotinylated antibodies against C4 as detecting antibodies we developed an ELISA for the quantification of C4b/c in biological fluids. The lower limit of detection was approximately 0.025 nmol C4b/c per litre. Mean C4b/c levels in plasma samples collected from healthy volunteers in tubes containing 10 mM EDTA and 0.05% (w/v) polybrene, final concentrations, appeared to be 30 nmol/l. The potential of the ELISA procedure for evaluating complement activation in clinical samples was demonstrated.

Animals↗