Pancreatic transplantation in patients with type-I diabetes: the experience in Maastricht with a new model.

A successful pancreatic transplant together with a kidney graft makes type-I diabetic patients with end-stage diabetic nephropathy independent from insulin and dialysis. Several surgical techniques for the pancreatic graft are employed. Major problems are thrombosis of the graft and the handling of the exocrine secretion of the pancreas.

A new variant for whole pancreas grafting.

A new variant for whole pancreas grafting is described in which a segment of the duodenum and the spleen is included in the graft. The graft is placed extraperitoneally as in kidney transplantation. The exocrine drainage is with side-to-side anastomosis between duodenum and bladder.

In vivo dynamic 99mTc-HIDA scintigraphy after hepatocyte transplantation: a new method for the monitoring of graft function.

In vivo dynamic 99mTc-HIDA scintigraphy was tested as a method for graft function monitoring after hepatocyte transplantation (HTX). Bilirubin uridyldiphosphate glucuronyl transferase-deficient rats received 10(7) viable isolated hepatocytes from congenic nondeficient donors by intrasplenic injection. The transplanted rats were divided into 2 groups.

2'Deoxycoformycin and deoxyadenosine affect IL 2 production and IL 2 receptor expression of human T cells.

Congenital deficiency of the enzyme adenosine deaminase (ADA) leads to severe combined immunodeficiency. 2'Deoxycoformycin (dCF), a tightly binding inhibitor of ADA, can induce the metabolic state of ADA deficiency. In vivo, the drug causes specific impairment of lymphocyte function and shows strong immunosuppressive properties.

T-cell-independent macrophage activation in mice induced with rRNA from Listeria monocytogenes and dimethyldioctadecylammonium bromide.

Purified rRNA from Listeria monocytogenes or Pseudomonas aeruginosa injected in combination with dimethyldioctadecylammonium bromide (DDA), protects mice nonspecifically against a lethal challenge of various extra- and intracellular bacteria. In the present study vaccination of BALB/c as well as C57BL/Ka mice with listerial RNA-DDA resulted in activation of fixed-tissue macrophages, as measured by an enhanced in vivo L. monocytogenes killing in spleen and liver.

Hepatocyte transplantation for enzyme deficiency disease in congenic rats.

Long-term effects of hepatocyte transplantation (HTX) in the treatment of enzyme deficiency disease were studied. Congenic enzyme-deficient (R/APfd-j/j) and non-enzyme-deficient (R/APfd) rats were used as recipients and donors, respectively. The R/APfd-j/j rat strain is congenitally deficient of bilirubin uridyldiphosphate (UDP)-glucuronyl transferase.

Fibronectin levels in stressed and septic patients fed with total parenteral nutrition.

Plasma fibronectin concentrations were measured in healthy persons as well as in septic and stressed patients. A decrease in plasma fibronectin concentration was shown in volunteers receiving a low energy (600 kcal), amino acids- and lipid-deficient diet. Increased fibronectin levels were measured in stressed and septic patients, not receiving enteral nutrition, after adequate total parenteral nutrition (TPN during 1 week).

Supernatants of human leukocytes contain mediator, different from interferon gamma, which induces expression of MHC class II antigens.

In this report, data are presented on the regulation of MHC class II antigen expression by a mediator present in supernatants of human mixed leukocyte cultures (MLC-SN), and which is different from IFN-gamma. The capacity of supernatants to induce antigen expression did not correspond to titers of IFN-gamma. Removal of IFN-gamma using either dialysis against pH 2 or neutralizing mAb against human IFN-gamma did not abrogate the MHC class II antigen expression-inducing capacity of MLC-SN when tested on adenocarcinoma cell lines, kidney epithelial cells, and fibroblasts in vitro in an indirect immunofluorescence assay.

Alloantigen presentation by canine endothelial cells. Presentation of autologous alloantigens in vitro.

Presentation of autologous alloantigen by certain cells in an allograft can result in allograft rejection. The precise type of cell in a graft responsible for this aspect of allograft rejection remains to be established. Here we report the capacity of canine venous endothelial cells to activate, in vitro, allogeneic lymphocytes for proliferation and differentiation by presentation of alloantigen.

Cyclosporin A inhibits IL 2-driven proliferation of human alloactivated T cells.

The influence of cyclosporin A (CsA) on the interleukin 2 (IL 2)-driven proliferation of allo-activated human T lymphocytes has been studied. CsA (50, 100, and 250 ng/ml) appeared to affect the IL 2-driven proliferation. The impaired proliferation could not be reversed with exogenous interferon-gamma.

Canine MHC-class II antigens on B and T lymphocytes.

MHC-class II antigens on canine lymphoid cells were detected with monoclonal antibodies (Mabs). On the basis of reactivity with resting or activated T lymphocytes two groups of Mabs were reported earlier. Non-activated T lymphocytes expressed MHC-class II antigens recognized by the first group whereas the second group recognized only MHC-class II antigens on activated T lymphocytes.

Local treatment of renal allografts, a promising way to reduce the dosage of immunosuppressive drugs. Comparison of various ways of administering prednisolone.

A method is described for continuous administration of immunosuppressive drugs directly into rat renal allografts. The drug is given via a catheter, introduced into the suprarenal or testicular artery of the transplanted kidney. The cannula is connected to an implantable osmotic minipump that delivers an immunosuppressive drug with continuous flow for 13 days.

Analysis of cytotoxic T lymphocyte response in rejecting allografted canine kidneys.

The involvement of cytotoxic T lymphocytes (CTL) in the rejection process of allografted canine kidneys was studied. The frequency of donor-specific (precursor) CTL was determined with a sensitive limiting dilution assay. Longitudinal sampling of peripheral blood and kidney aspiration biopsies were used to obtain information on the CTL response toward the graft.

Joint report of the Third International Workshop on Canine Immunogenetics. I. Analysis of homozygous typing cells.

The Third International Workshop on Canine Immunogenetics involved 80 potentially DLA-D homozygous typing cells obtained from dogs of various breeds and submitted from five laboratories in Europe and the United States. Mutual reactivity of all cells was studied in mixed leukocyte cultures, and stabilized relative responses were used for analysis. Intralaboratory and interlaboratory comparisons of results suggest that a stabilized relative response of 30% represents an acceptable parameter for "typing responses" indicating phenotypic DLA-D identity of stimulator and responder cells.

Activation through CD3 molecule leads to clonal expansion of all human peripheral blood T lymphocytes: functional analysis of clonally expanded cells.

Monoclonal antibodies directed against CD3, a T cell-specific surface molecule essentially required for activation of these cells, are highly mitogenic for resting human peripheral blood T lymphocytes. A predetermined optimal concentration of anti-CD3 monoclonal antibody WT32 was employed to activate T cells cultured in limiting-dilution microcultures containing irradiated feeder cells and exogeneous interleukin 2. Frequencies of cells triggered into clonal expansion by WT32 under these culture conditions were 0.

Lymphokines induce changes in morphology and enhance motility of endothelial cells.

The influence of lymphokines, the soluble mediators produced by lymphocytes, on the morphology and the motility of endothelial cells in vitro is described. Lymphokines induced an altered morphology and an increased motility of canine and human venous endothelial cells. The action of the lymphokines was species specific.

Treatment of enzyme deficiency by hepatocyte transplantation in rats.

The inbred, homozygous Gunn rat exhibits unconjugated hyperbilirubinemia due to a hereditary absolute deficiency of bilirubin UDP-glucuronyltransferase activity. The mechanism of action of hepatocyte transplantation (HTX) in the treatment of enzyme deficiency has been investigated in this study. Gunn rats underwent HTX by the injection of isolated hepatocytes from a nondeficient donor rat (Wistar) into the spleen.

Complete suppression of skin allograft rejection in rats treated with continuous infusion of 2'deoxycoformycin.

Congenital deficiency of the enzyme adenosine deaminase (ADA) results in severe combined immunodeficiency. 2'deoxycoformycin (2'dcf) is a tightly binding inhibitor of ADA, and the drug makes it possible to mimic a state of ADA deficiency. In this study we tested the immunosuppressive effect of 2'dcf in a rat skin transplantation model.

Lymphokine dependence of in vivo expression of MHC class II antigens by endothelium.

Changes in the expression of class II antigens of the major histocompatibility complex (MHC) have an integral role in the regulation of immune responses, and are brought about in vitro by soluble mediators. However, the mechanism that underlies in vivo expression of MHC class II antigens in, for example, endothelial cells in the absence of immunological stimulation has not been studied. We demonstrate here that expression of MHC class II antigens is not a constitutive property of endothelial cells, for MHC class II antigen-positive endothelial cells do not express these antigens during treatment with the immunosuppressive agent cyclosporin A.

Effect of cyclosporine on MHC class II antigen expression on arterial and venous endothelium in vitro.

MHC class II antigens play a crucial role in immunological responses. The expression of MHC class II antigens on monocytes and endothelial cells is reported to be variable and able to be induced by gamma-interferon. In this study we report on MHC class II antigen expression in vitro by arterial and venous canine endothelial cells, as detected with FACS analysis and indirect immunofluorescence with a monoclonal antibody against canine MHC class II antigens.

Cell-mediated cytotoxicity patterns of cloned cytotoxic T lymphocytes. Cytotoxicity directed against canine lymphoblasts, monocytes, and endothelial cells.

Knowledge of the antigens recognized during allograft rejection is still incomplete. Cloned cytotoxic T lymphocytes were used to study the distribution of target determinants in the dog. CTL clones were obtained with a limiting dilution technique from effector cells generated in mixed lymphocyte culture.