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H Bitter-Suermann

Publications and source records attributed to H Bitter-Suermann.

At least 55 records · Page 3Linked to original sources

Induction of transplantation tolerance in rats by spleen allografts. I. Evidence that rats tolerant of spleen allografts contain two phenotypically distinct T suppressor cells.

We have examined suppressor cell activity in transplantation tolerant (TT) rats bearing vascularized spleen allografts in several different donor-recipient combinations. More than 60% of WAG (RT-1u) and 65% of AGUS (RT-1l) spleen allografts were permanently accepted when transplanted to AGUS and PVG (RT-1c) rats, respectively. All (WAG X AGUS)F1 to AGUS and (AGUS X PVG)F1 to PVG spleen allografts survived indefinitely. Unseparated LNC, TDL, and whole T cell or W3/25+, OX8- T cell populations obtained from AGUS rats bearing (WAG X AGUS)F1 spleens exhibited reduced mixed lymphocyte reaction (MLR) responses to the spleen donor, and to some extent to BN(RT1n) third-party stimulators, but responded normally to PVG.A(RT1a) stimulators. Coculture experiments demonstrated that lymph node cells (LNC) and thoracic duct lymphocytes (TDL) of TT rats contain RT1 specific suppressor cells. Furthermore, T cells isolated from all donor-recipient combinations contained two phenotypically distinct suppressor cell populations: a radiosensitive W3/25+, OX8- (Th/i) and a relatively radioresistant W3/25-, OX8+ (Ts/c). These Ts may be responsible for the maintenance of TT.

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Streptozotocin diabetes in juvenile pigs. Evaluation of an experimental model.

Spontaneous diabetes in the domestic pig, an animal suitable for metabolic and endocrine studies and for experimental surgery, is extremely rare. In this study we have compared the diabetogenic response of various doses of streptozotocin in comparison to surgically induced diabetes. Streptozotocin in a low dose, 35 mg/kg body weight did not influence glucose metabolism while an intermediate dose, 85 mg/kg, resulted in a transient diabetic reaction. Streptozotocin, 100-150 mg/kg body weight, caused a complete and permanent diabetes. Animals made diabetic by means of pancreatectomy did not survive more than 10 days due to their poor general condition and diabetes. Streptozotocin induced diabetic animals survived with insulin treatment up to seven months. The results show that juvenile pigs made diabetic with 100-150 mg/kg body weight of streptozotocin may be useful in experimental work on glucose-, insulin- and C-peptide-metabolism in a large animal. Therefore it is potentially useful in pancreatic transplantation research.

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Conversion from cyclosporine to azathioprine in renal graft recipients.

Only one of six patients in whom a clinical diagnosis of rejection was confirmed by both biopsy and FNA benefited from a switch from cyclosporine to azathioprine. Nine patients, in whom nephrotoxicity and rejection could not be separated and in whom the biopsy was positive but the FNA negative, improved when converted to cyclosporine. This improvement was, however, followed by subsequent rejection episodes in four of these patients. This study suggests caution in changing from CsA therapy in patients with unstable function.

Azathioprine↗

Suppressor cells in the thoracic duct lymph of tolerant, spleen-grafted rats.

Vascularized spleen allografts between two different inbred rat strains induce specific transplantation tolerance in vivo. Thoracic duct lymphocytes isolated from tolerant rats exhibited notable nonresponsiveness to donor stimulator cells in the mixed lymphocyte reaction. In-vitro co-culture experiments indicate that this nonresponsiveness reflects the activity of both specific and nonspecific suppressor cells. Since suppressor cells are present in tolerant animals, it is possible that the suppressor cells play an important role in maintaining spleen-induced transplantation tolerance.

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Induction of transplantation tolerance in guinea pigs by spleen allografts. III. Transfer of tolerance to normal hosts.

Spleen allografts from (2 X 13)F1 donors survive indefinitely in immunologically intact strain 2 recipients. Such strain 2 hosts with long-term surviving F1 grafts had markedly suppressed anti-13 MLR responses and cells capable of suppressing the response of normal strain 2 cells to strain 13 stimulators were present in some long-term surviving animals. In order to further analyze the cellular basis for this tolerant state, we transferred cells from tolerant donors to normal syngeneic strain 2 hosts. We showed that such suppressor cells transfer MLR unresponsiveness to primary or secondary hosts, but that the period of MLR suppression is rather short-lived. Strain 13 cardiac allografts survived indefinitely in cell-transferred primary or secondary hosts and further enhanced MLR suppression, whereas most cardiac allografted controls had vigorous MLR responses for strain 13 stimulator cells after rejection of their transplants. Attempts to abrogate established tolerance in transferred hosts, either by donor antigen or by host cytolytic T cells were unsuccessful.

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Induction of transplantation tolerance in guinea pigs by spleen allografts. I. Operative techniques and clinical results.

Four hundred and ten heterotopic spleen transplants were performed in inbred guinea pigs of strains 2 and 13 whose major histocompatibility complex differs only in the I region and which rapidly reject reciprocal skin allografts. Spleen allografts from strain 13 to strain 2 survived throughout the lifetime of the hosts, whereas spleen allografts from strain 2 to strain 13 were rejected within 3 weeks. Animals not rejecting their spleen transplants were specifically tolerant of donor strain skin allografts. Strain 2 recipients of strain 13 spleen grafts had a surprising high mortality from graft-versus-host disease which peaked at 6 weeks after transplantation.

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Induction of transplantation tolerance in guinea pigs by spleen allografts. II. Responses in the mixed leukocyte reaction correlate with the tolerant state.

We have developed a model for the induction of transplantation tolerance in the guinea pig by vascularized spleen allografts. Spleen allografts from strain 13 to strain 2 hosts frequently survived in healthy recipients without clinical GVHD or induced clinical GVHD. (2 x 13)F1 to strain 2 spleen allografts survived indefinitely without inducing GVHD. In contrast, strain 2 spleen allografts were rejected by strain 13 hosts. An excellent correlation was observed between the clinical course and the degree of reactivity to donor strain stimulator cells in the MLR. Animals that had rejected their grafts had normal or enhanced proliferative responses in the MLR. Strain 2 hosts with long-term surviving strain 13 or (2 x 13)F1 grafts had markedly suppressed anti-13 responses. Animals with GVHD had a suppressed MLR toward donor strain stimulator cells with simultaneous reactivity to host strain stimulator cells. Cells capable of suppressing the response of normal host strain cells to donor strain stimulators were present in some long-term surviving animals and may be responsible in part for the maintenance of the tolerant state.

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Morphological findings in duct-ligated pancreas grafts in the rat. An analysis of isografts, allografts, and long-standing allografts in hosts conditioned by previous spleen allograft.

The morphological findings of duct-ligated pancreas grafts in streptozotocin-induced diabetic hosts were studied using inbred AGUS and WAG rats with a major histocompatibility complex differences. AGUS to AGUS pancreas isografts survived indefinitely. Morphologically, islet tissue was partly dispersed and showed about 75% granulated beta cells. Fibrosis was minimal and inflammatory cells generally absent. WAG to AGUS allografts were quickly rejected and showed severe pancreatitis with a polymorphonuclear and mononuclear infiltrate. Islet destruction lagged behind that of exocrine tissue and vascular thrombosis was a late event. In the last group, AGUS recipients first received WAG spleen allografts which survived spontaneously. There to 5 months later they were removed and WAG pancreas allografts inserted. Sixty-eight percent of these pancreas allografts survived. Four to 10 months later they were characterized by severe dense fibrosis surrounding islet tissue. Capillaries were always present between islet cells, about 75% of which showed beta granules. A mild to moderate mononuclear cell infiltrate and vascular intimal proliferation were also part of the picture. We conclude that pancreatitis after duct-ligated pancreas allografts is not a sequel of duct ligation but results from rejection and can be prevented with adequate immunosuppression. Fibrosis does not have a detrimental effect on islet cell function as a result of the feasibility of insulin secretion by beta cells into adjacent capillaries and thence to larger vessels traversing through the dense fibrosis.

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The course of pancreas allografts in rats conditioned by spleen allografts.

A new technique for transplanting duct-ligated rat pancreas grafts, rather similar to the technique for spleen grafting in rats, is presented. Inbred AGUS and WAG rats with a strong Ag-B incompatibility were used. Duct-ligated pancreas AGUS to AGUS isografts survived indefinitely in streptozotocin-induced diabetic hosts while WAG to AGUS allografts were quickly rejected. However, when WAG spleen and pancreas were transplanted en bloc to AGUS rats, endocrine pancreas graft function persisted for up to 6 weeks. This finding of a transient protection of pancreas allografts by donor-strain spleen allografts led to further experiments. AGUS recipients first received WAG spleen allografts which then were removed after 3 to 5 months, at which time WAG pancreas allografts were inserted. Sixty-eight per cent of these grafts survived and cured their hosts of streptozotocin-induced diabetes.

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Surgical aspects of spleen grafting in rats.

Grafting of the spleen as an organ of full immunological competence in inbred rats was found to be a useful tool for studies of immunological parameters, which would be difficult to evaluate in outbred and larger animals. Early results indicate that the spleen is under certain circumstances less susceptible to rejection than other organs in the rat and knowledge about principles, underlying this phenomenon, might have application for grafting of organs in other species. Experimences gained in grafting more than 400 rat spleens heterotopically were described together with the technique employed.

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