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G Tufveson

Publications and source records attributed to G Tufveson.

At least 73 records · Page 4Linked to original sources
PubMed1994

Role of antibody synthesis and complement activation in concordant xenograft retransplantation.

A mouse-to-rat heart retransplantation model was used to study the effects of complement depletion and antibody production with regard to graft survival and anti-donor antibody specificity. Retransplantation was performed 3 weeks after the first transplantation in the presence of absence of 15-deoxyspergualin (DSG) immunosuppression. Untreated animals rejected their first graft after 3 days and retransplantation resulted in a hyperacute rejection within 2 min. A low titer of preformed anti-mouse lymphocytotoxic antibodies of the IgM subclass was found in serum collected from the unoperated rat. The rejection gave rise to a synthesis of IgG antidonor antibodies reacting with both graft endothelium and sarcolemma. Immunofluorescent staining of the rejected first heart graft showed moderate IgM and IgG antibody deposits on the graft vascular endothelium, while only IgG was found in the second graft. There was no C3 deposition found in the first mouse graft, as was the case in the second mouse graft. Anti-mouse antibodies cross-reacted with hamster antigens and a hyperacute rejection of a hamster heart graft occurred in a mouse-sensitized rat. Immunofluorescent staining revealed that the antibodies did not bind to hamster heart endothelium, as was expected, but, instead, to graft sarcolemma. DSG treatment prolonged the survival of the first graft by a median of 8 days. Continuous treatment until retransplantation resulted in a prolongation to 30 (20-127) min of the survival of the second graft and no increase in antibody titers against mouse antigens was observed. However, immunofluorescent staining revealed a weak binding of anti-mouse antibodies of the IgM subclass in the rejected mouse heart graft. Additional complement depletion with cobra venom factor in DSG-treated animals resulted in a prolongation of the median graft survival to 48 hr (6-96). No sign or minimal signs of antibody deposition were found in these grafts, but histology revealed massive mononuclear infiltration. In conclusion, xenograft transplantation in a concordant situation results in a shift of antidonor antibody Ig synthesis from IgM to IgG. If daily DSG treatment is administered from the day of transplantation, this reduces the synthesis of antidonor antibodies, and if complement is also depleted, the survival of the second graft is prolonged. The significance of the mononuclear infiltration remains to be established.

Animals↗
PubMed1994

Partial inhibition of allograft arteriosclerosis (chronic rejection) by 15-deoxyspergualin.

15-deoxyspergualin (DSG) is an immunosuppressive drug that suppresses monocyte/macrophage function and/or T cell induction and early differentiation of B lymphocytes. It is as effective as cyclosporine in the prevention of acute rejection. We have investigated the effects of DSG on rat aortic allograft arteriosclerosis (chronic rejection). DSG was administered to the recipient rat at a dose of 0.3-10 mg/kg/day i.p. for 1-3 months, after which recipients were sacrificed. Histological changes were quantitated from paraffin sections. DSG is effective in chronic rejection in rat aortic allografts and reduces all three manifestations in the vascular wall--adventitial inflammation, media necrosis, and intimal thickening. At the dose of 1.0 mg/kg/day we demonstrated significant inhibition of adventitial inflammation from 10.6 point score units (psu) to 4.7 psu (P < 0.05), of media necrosis (P = 0.004) and of intimal thickening from 2.9 psu to 0.8 psu (P = 0.008). The therapeutic window was small in the long-term experiment. Doses of 3-10 mg/kg/day were toxic and 0.3 mg/kg/day was ineffective. In vitro smooth muscle cell proliferation was not inhibited by DSG and in the in vivo carotic denudation model DSG had no inhibitory effects either. These results suggest that DSG works via suppression of the immune/inflammatory response rather than via a direct antiproliferative effect on smooth muscle cells.

Animals↗
PubMed1994

A randomized multicenter trial of cyclosporin and prednisolone versus cyclosporin, azathioprine, and prednisolone following primary living donor renal transplantation.

A total of 195 consecutive recipients of primary living donor renal transplants were randomized to receive either cyclosporin (CyA) and prednisolone (double therapy) or CyA, prednisolone, and azathioprine (triple therapy). There was no significant difference in patient or graft survival, incidence of acute rejection episodes, or major complications between the groups. The graft survival at 5 years was 71.5% in patients receiving double therapy and 71.6% in patients receiving triple therapy. In a Cox regression analysis, recipient age and occurrence of acute rejection were the only independently significant variables affecting graft survival, whereas treatment schedule did not. Renal function was stable throughout the observation period and did not differ between the double and triple therapy groups. A linear regression analysis showed that recipient age, donor age, gender, and occurrence of acute rejection significantly influenced the serum creatinine level. This and previous similar prospective studies in cadaveric renal transplantation indicate that there is no advantage of routinely adding azathioprine to a double drug regimen.

Adult↗
PubMed1994

Quantitative measurements of collateral arterial blood flow in nonarterialized rat liver grafts.

The early development of arterial blood flow in the grafted liver after orthotopic liver transplantation in the rat without reconstruction of the hepatic artery was studied. Arterial liver blood flow was measured on day 21 after transplantation with NEN-TRAC microspheres (size 15.5 +/- 0.1 microns) and labelled with 103Ru. The arterial liver blood flow in the grafted liver was 0.778 +/- 0.247 ml/min per gram for transplanted rats after 21 days. One day after transplantation, the blood flow was only 0.006 +/- 0.002 ml/min per gram. The results of this study demonstrate that there was no arterial blood flow on day 1 after transplantation, as expected, but that there was a high arterial blood flow in the transplanted liver by day 21. This was also supported by the angiographic findings. The early development of arterial blood flow via collaterals may account for the excellent results that we and others have attained in orthotopic liver transplantation without rearterialization in the rat.

Animals↗
PubMed1994

MC 1288--a vitamin D analogue with immunosuppressive effects on heart and small bowel grafts.

The vitamin D analogue MC 1288 (20-epi-1 alpha,25-dihydroxycholecalciferol) was tested here for its possible immunosuppressive properties in vivo using different rat transplantation models. MC 1288, in a dose of 0.1 microgram/kg daily, administered intraperitoneally for 10 days, was found to be effective in prolonging cardiac allograft survival. Untreated recipients rejected their grafts around day 8 while MC 1288 treatment delayed rejection until day 22 (P < 0.001). Addition of the immunostimulatory drug LS-2616 (Linomide) reduced the immunosuppressive effect of MC 1288 and rejection occurred around day 11. The immunosuppressive effect of MC 1288 on rejection following small bowel transplantation was determined by measuring the amounts of hyaluronan (HA) secreted into the intestinal lumen. On day 6 post-transplantation the amounts of intraluminal HA in untreated animals was 29.2 +/- 5.3 ng/min and cm, while in MC 1288-treated animals it was just 5.0 +/- 1.6 ng/min and cm (P < 0.01). We conclude that MC 1288 has immunosuppressive effects that may make it suitable for the prevention of graft rejection.

Adjuvants, Immunologic↗
PubMed1994

The immunomodulator LS-2616 (linomide) more effectively than sensitization of the donor enhances graft-versus-host reaction after small bowel transplantation.

The effects of the immunomodulating substance LS-2616 (linomide) on graft-versus-host reaction (GVHR) were investigated in a semi-syngeneic small bowel transplantation model. The entire bowel of Lewis donors were transplanted heterotopically into (Lewis x BN) F1 hybrids. Both untreated animals and animals treated with LS-2616, in a daily dose of 160 mg/kg, developed a lethal GVHR. The median survival time in untreated animals was 14.5 days while in LS-2616 treated animals it was just eight days (p < 0.01). LS-2616 in combination with cyclosporin A (CyA), 15 mg/kg given orally on days 0-20, did not seem to alter the survival times compared with CyA treatment alone; 56% of the animals treated with CyA survived for more than 100 days and after combined treatment with CyA/LS-2616 there were 50% permanent survivors. Also the effect of earlier sensitization of the donor on the course of GVHR was investigated. Hearts from BN rats were transplanted heterotopically to the neck vessels of Lewis rats. The hearts were rejected on about day six; five days later the bowels were harvested and transplanted into (Lewis x BN) F1 hybrids. The median survival time in this group was 12.5 days. Taken together our results, in combination with earlier findings, suggest that, at the level of effector mechanisms, GVHR is not an exact mirror image of rejection. Also, LS-2616 appears to be a useful tool for further studies of the mechanisms of action of GVHR.

Adjuvants, Immunologic↗
PubMed1994

HLA-A incompatibility associated with enhanced long-term renal graft survival in HLA-B, DR mismatched transplants.

The effect of HLA-A matching on long-term cadaver kidney graft survival was analysed, on average, 6 years after transplantation in a total of 1085 cyclosporine (CyA)-treated patients. A beneficial effect of HLA-A mismatching on graft survival was found by univariate and multivariate analyses (P < 0.05). Enhanced graft survival was associated with HLA-A mismatching in transplants mismatched for HLA-B,DR (P = 0.03), but not in HLA-B,DR compatible transplants. High 6 year graft survival rates, 78% and 66%, were found in transplants mismatched for two or one HLA-A antigens, respectively, among patients without any acute rejection episode. This was significantly higher than the survival rate of 55% found in HLA-A compatible transplants (P = 0.001). In patients who had suffered from acute rejection episodes, a prolonged graft survival was also associated with HLA-A mismatching in HLA-B,DR mismatched transplants (P = 0.04). The beneficial effect on graft survival of HLA-A mismatching was most pronounced in patients treated with high/medium dose CyA and prednisolone (P = 0.004 overall and P = 0.0007 for HLA-B,DR mismatched transplants). In conclusion, HLA-A mismatching was associated with enhanced long-term renal graft survival in CyA-treated recipients of HLA-B,DR mismatched transplants. In clinical situations, the present results might, if confirmed, contribute to the prolongation of long-term graft survival. The results might indicate the existence of tolerance promoting allogeneic markers within the HLA-A class I region.

Diabetes Mellitus↗
PubMed1994

Characterization of the anti-A antibody binding in an ABO-incompatible living donor renal transplantation.

A 57-year-old female, blood group B, with polycystic kidney disease, received an ABO-identical, HLA-A,B,DR 5-mismatched renal allograft in 1986. Due to graft artery thrombosis and vascular rejection, she lost the kidney 6 months after transplantation and developed HLA antibodies with a panel reactivity of 99%. Despite 5 years on a European waiting list for highly immunized patients, she was not offered a second kidney. An attempt to remove her HLA antibodies by plasmapheresis combined with cyclophosphamide therapy did not succeed. Her 53-year-old HLA-identical, but ABO-incompatible sister (blood group A1), was then accepted as a donor. After immunoadsorption on Biosynsorb-A columns, transplantation was performed. The post-transplant course was uneventful without any signs of rejection. Studies on the anti-A antibody binding characteristics before and after immunoadsorption and after transplantation, showed that IgM and IgG antibodies recognizing the A trisaccharide epitope based on the type 1, 2, and 4 core saccharide chains, were effectively removed by Biosynsorb-A adsorption, but the column failed to remove anti-A antibodies recognizing the A type 3 antigen. These antibodies probably requires part of the core saccharide chain for binding. The presence of these antibodies did not seem to influence the outcome of the ABO-incompatible transplantation.

ABO Blood-Group System↗
PubMed1994

Effect of 15-deoxyspergualin on allograft arterio-sclerosis and growth factor synthesis in the rat.

Chronic rejection is a major cause for late graft loss. Typical vascular changes in the grafts are adventitial inflammation, disappearance of myocytes in the media and thickening of the intimal layer. We investigated the effect of a new immunosuppressive drug, 15-deoxyspergualin (DSG), on chronic rejection using our rat aortic allograft model. At the dose of 1.0 mg/kg per day, DSG significantly reduced all histopathological parameters of chronic rejection, thus, inhibiting the generation of allograft arteriosclerosis. Growth factor synthesis in the grafts was determined by reverse transcription reaction with oligo dT primers and semiquantitated by polymerase chain reaction. The expression of several growth factors, PDGF-BB, IGF-1, EGF an TGF-beta, was suppressed to 16-60% of the non-treated allograft level. This indicated that DSG may work via suppression of growth factor synthesis and, thus, inhibits the generation of chronic rejection.

Animals↗