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Biomedical subjects

G Tufveson

Publications and source records attributed to G Tufveson.

At least 55 records · Page 3Linked to original sources
PubMed1996

Anti-carbohydrate antibodies associated with hyperacute rejection in a vascularized mouse heart-to-rat xenotransplantation model.

Specificity of immune reactions has always been sought, because it facilitates intervention with unwanted mechanisms. Specific carbohydrate antigens have been proposed to be targets of antibodies in early immune responses in pig-to-man xenografts. This work was undertaken to determine carbohydrate structure for antibody response in the experimental xenograft model mouse-to-rat. Glycolipids were prepared from nine different mouse organs and separated for carbohydrate size on thin layer plates. Sera taken from normal untreated rats showed only weak or absent IgM antibody-binding to the separated mouse glycolipids. This is in accordance with the observation that mouse heart grafts are not hyperacutely rejected by the rat. However, sera taken from mouse heart xenografted rats show clear IgG and IgM antibody binding to neutral glycolipids migrating in the five-sugar region of the thin-layer plate. These rats have previously been reported to hyperacutely reject a second xenograft. Glycolipids with this particular mobility and immunostaining properties are the dominant ones in the mouse caval vein preparation, which probably represents a rather pure vascular structure. The target antigen structure was identified, by mass spectrometry and proton nuclear magnetic resonance spectroscopy, to be the Forssman pentaglycosylceramide. A commercial monoclonal antibody directed toward the Forssman antigen bound the same biochemical structure as the antibodies derived from the mouse heart-xenografted rats. Most of the IgM activity, but very little of the IgG activity was adsorbed using the Forssman terminal disaccharide solid phase.

Acute Disease↗
PubMed1996

Is kidney transplantation in sensitized recipients justified?

The objective of the study was to determine if it is justified to use the scarce resources of cadaveric kidneys on HLA-sensitized patients, by reviewing the initial and long-term outcome of cadaveric renal transplantation at Uppsala University Hospital, Sweden. Between January 1988 and December 1994, 402 renal transplantations were performed. The patients were divided into one group of sensitized recipients (peak panel antibody reactivity > or = 25%; n = 84) and a second of non-sensitized recipients (panel reactive antibodies < 25%; n = 318). The groups were comparable in terms of recipient and donor age, gender, HLA-A, -B and -DR mismatches and numbers of diabetics. None of the sensitized patients received a six-antigen-matched kidney. For the non-sensitized group, life table analysis showed a 1-year actuarial graft survival (GS) of 91.8% and a 4-year GS of 84.4%. The corresponding GSs for the sensitized group were 79.9% and 68.7%, respectively (P < 0.01). The statistical significance vanished if patients with primary non-function were excluded. When excluding donors above 55 years of age, kidneys with cold ischemia time above 20 h, and two-antigen (HLA-DR) mismatches, there was no detectable difference between the non-sensitized and sensitized groups at 1-year or 4-year GS. Although there is a statistical significance in GS between non-sensitized and sensitized recipients of a kidney transplant, this does not differ from other risk groups such as diabetics, rheumatoid disease sufferers or elderly recipients. We therefore conclude that the sensitized patient should be accepted on the waiting list for a kidney transplant and that it is worthwhile to do the utmost to transplant this category of patients. Our data indicate that kidney GS in sensitized recipients is more affected by negative risk factors such as older donors, long cold ischemia time and two-antigen HLA-DR mismatch, than the non-sensitized recipient. To improve the outcome, those negative factors should be avoided or reduced.

Adult↗
PubMed1996

Cytomegalovirus (CMV) DNA amplification from plasma compared with CMV pp65 antigen (ppUL83) detection in leukocytes for early diagnosis of symptomatic CMV infection in kidney transplant patients.

BACKGROUND: Rapid laboratory methods for the early detection of cytomegalovirus (CMV) are needed for the prevention of CMV disease in transplant recipients. These methods should not only be able to detect the virus but also be highly predictive for CMV disease. OBJECTIVE: The clinical value of a simple and rapid nested plasma polymerase chain reaction (PCR) was evaluated by comparing the results with CMV pp65 antigen detection in leukocytes (CMV antigenemia assay), virus isolation from leukocytes, CMV IgG and IgM antibody response and clinical data. STUDY DESIGN: A total of 471 EDTA blood samples were collected from 85 kidney transplant patients during a 3-4 month period after transplantation. CMV DNA was amplified directly from 10 microliters of plasma while 150000 separated leukocytes were stained for CMV pp65 antigen by each of two monoclonal antibodies. A total of one million leukocytes were used for virus isolation. The PCR protocol used in the present study involves a simple alkaline lysis technique for isolating DNA directly from plasma which is easy and rapid to perform. RESULTS: Twenty-eight patients developed symptomatic CMV infection while asymptomatic infection occurred in 29 patients. CMV pp65 antigen detection had a 75% sensitivity and a 57% positive predictive value for CMV disease development, compared with 64% and 79% sensitivity and 49% and 46% positive predictive value for CMV DNA and viremia, respectively. The median time until detection of CMV in patients with symptomatic CMV infection was 26 days after transplantation, compared with 49 days in asymptomatic patients by any of the methods used. Early appearance (within 8 weeks) of CMV pp65 antigen and CMV DNA had high predictive values for symptomatic infection; repeated detection of pp65 antigen and CMV DNA were more common in symptomatic patients. CONCLUSIONS: CMV antigenemia assay and plasma PCR can be used for pre-symptomatic diagnosis of CMV infection. Virus isolation and CMV serology in most cases provide a post-symptomatic diagnosis. The best marker for monitoring kidney transplant patients might be the quantitative CMV antigenemia assay.

Adolescent↗
PubMed1996

Moderate additive immunosuppressive effect of thalidomide combined with cyclosporin A in rat cardiac transplantation.

Thalidomide is an immunomodulating agent shown to prolong graft survival in experimental skin, renal, cardiac and bone marrow transplantation. The main purpose of the present study was to investigate the possible additive effect of combining thalidomide with cyclosporin A (CyA). Members of our group have previously created a basis for such studies by demonstrating the ability of Linomide to abolish the effect of CyA. The additional effect of combined treatment with a second drug is thereby more readily evaluated, compared with using subtherapeutic dose levels to induce early rejection. Cardiac grafting was performed in three rat strain combinations (BN to WF, DA to Lew, and BN to Lew). Rats were given no treatment, or thalidomide, CyA and/or Linomide in single, double or triple drug therapy. Except for a consistent beneficial effect of CyA as single drug treatment, graft survival varied depending on the rat strain combination used. In the DA to Lew combination, the expected effects of Linomide were seen, and thalidomide was shown to prolong graft survival significantly (P = 0.004) when added to CyA and Linomide. However, there was no effect of thalidomide when given alone. In WF recipients of BN hearts, thalidomide tended to prolong graft survival (P = 0.07), and surprisingly Linomide manifested a marked immunosuppressive effect (P = 0.0002) and did not counteract the effect of CyA. When transplanting BN grafts to Lew recipients, Linomide reduced significantly but did not abolish completely the effect of CyA. Neither Linomide nor thalidomide had any beneficial impact on graft survival on their own. To sum up, thalidomide was shown to have a minimal or moderate immunosuppressive effect additive to that of CyA. The effects of the two immunomodulating drugs, thalidomide and Linomide, varied depending on the rat strain combination used, and were similar with respect to prolongation of graft survival when used as single drug treatment in BN to WF grafting, a fact which may indicate them to have a similar mechanism of action, both having been shown to exert similar effects on levels of tumour necrosis factor alpha.

Adjuvants, Immunologic↗
PubMed1996

Experimentally-induced warm renal ischemia induces cortical accumulation of hyaluronan in the kidney.

An accumulation of the connective tissue component, hyaluronan (HA), is known to occur in both syngeneic and allogeneic kidney grafts during the early postoperative period. The presence of HA in the interstitial tissue of the grafts is paralleled by an increased water content, suggesting a role for HA in the development of the transplantation edema. In the present work, the kidney content and distribution of HA was studied in a model of warm renal ischemia in the rat to investigate whether renal ischemia is associated with HA accumulation. Seventy-two hours after a period of warm renal ischemia (30 or 60 min) significantly higher amounts of HA were observed in the left kidney that had been exposed to ischemia, than in the right, healthy kidney. The most pronounced increase was found to occur in the cortex (20 to 40 times), a structure where there normally is almost no presence of HA. In addition, there was a correlation between the relative water content of the kidney and the amount of HA possible to extract from the tissue. The renal accumulation of HA and water was prevented by daily intravenous administration of hyaluronidase. We conclude that renal ischemia induces an accumulation of HA that may increase the risk for the development of interstitial edema, a situation that may be circumvented by hyaluronidase treatment.

Animals↗
PubMed1996

A prospective study of rapid methods of detecting cytomegalovirus in the blood of renal transplant recipients in relation to patient and graft survival.

Eighty-five renal transplant recipients were prospectively monitored for CMV infection up to 4 months post-transplantation by virus isolation from leukocytes, CMV antigen detection (pp65) in peripheral blood leukocytes (PBL), polymerase chain reaction (PCR) of alkaline treated plasma (P-PCR), PCR of extracted DNA from PBL (L-PCR) and serology. Additionally univariate and multivariate analyses of risk factors for patient and graft survival up to 4 yr post-transplantation were performed. The incidence of CMV infection was 78% and of CMV disease 33%. Antigen detection in PBL was positive before or at onset of symptoms in 23/24 (96%) evaluable patients with CMV disease. The corresponding figures for virus isolation were 22/24 (92%), P-PCR 21/24 (88%) and for L-PCR 18/24 (75%). The percentage of negative samples in patients without CMV disease was 89% for the antigen test, 92% for L-PCR and 83% for virus isolation and P-PCR. One rapid test (antigen test, P-PCR or L-PCR) was positive at a median of 16 d before the onset of symptoms. The antigen test was generally the first rapid test to become positive. CMV disease did not affect graft survival in the multivariate analysis but was associated with decreased patient survival.

Adolescent↗
PubMed1995

Ischemic heart disease--major cause of death and graft loss after renal transplantation in Scandinavia.

Causes of graft loss and death were studied in 1347 recipients of primary renal transplants followed for 5 years after transplantation irrespective of graft function. Immunosuppression consisted of high or medium dose CsA and prednisolone or low dose CsA and prednisolone and azathioprine. In recipients of cadaver grafts, death with a functioning transplant was more common than graft rejection after the first posttransplant year, accounting for 49% and 41% of the graft losses, respectively. Of deaths with a functioning graft, 53% were due to ischemic heart disease (IHD) and 10% were due to other vascular disease. In the 55- to 64-year-old age group, the risk of death from IHD was 6.4 times higher in the transplanted nondiabetic patients, 8.6 times higher in the dialysis patients (European Dialysis and Transplant Association figures), and 20.8 times higher in the transplanted diabetic patients than in the general population (national figures). A multivariate Cox regression analysis showed that old age, diabetes mellitus, occurrence of acute rejection, pretransplant transfusions, delayed onset of graft function, and male gender were significant for death in IHD. We conclude that, in comparison to reports from other regions, Scandinavian renal transplant recipients are at high risk of dying of IHD. Future advances in long-term renal graft survival will depend largely on the success of preventing myocardial infarction and death in this patient population.

Adult↗
PubMed1995

Simultaneous occurrence of rejection and graft-versus-host reaction after allogeneic small bowel transplantation.

Small bowel transplantation may be complicated not only by rejection but also by graft-versus-host reaction (GVHR). So far, little is known about the association between these two immunological reactions, partly because of the lack of standardized, reproducible experimental models for such studies. In this work, a rat model in which GVHR and rejection occur simultaneously was established. When transplanting small bowel grafts from BN donors to Lewis recipients and thereafter treating the grafts locally with the immunomodulating substance LS-2616, a clinically visible GVHR occurred on day 6, at the same time the first signs of rejection became visible. The GVHR was confirmed by immunohistochemical staining for MHC class II-positive cells in liver and ear skin biopsy specimens. An obvious quantitative difference in the number of positive cells in both organs was observed when local treatment was compared with oral LS-2616 treatment or with findings in organs from untreated animals. We conclude that GVHR and rejection are not mutually exclusive and thus may occur simultaneously, and that this pharmacological model might facilitate further studies of the impact of GVHR on graft rejection and recipient survival.

Adjuvants, Immunologic↗
PubMed1995

Enhancement of the immunosuppressive effect of cyclosporin A by ciprofloxacin in a rat cardiac allograft transplantation model.

Ciprofloxacin hyperinduces interleukin-2 production in stimulated human and mouse lymphocytes. In this study, an enhanced and prolonged interleukin-2 response was also detected in polyclonally stimulated rat splenocytes in the presence of ciprofloxacin (5-80 micrograms/ml) compared to control cells without any antibiotic. Ciprofloxacin was able to counteract the immunosuppressive effect of 10 ng/ml cyclosporin A (CyA) but did not interfere with higher CyA concentrations. In parallel, ciprofloxacin did not influence thymidine uptake in mixed lymphocyte reactions in the presence of CyA. To obtain an in vivo application of these findings, graft survival was studied by performing rat cardiac allograft transplantations in the presence or absence of CyA. Brown Norway rats served as donors and Wistar Furth rats as recipients. Ciprofloxacin was injected intraperitoneally either at a high-dose regimen (240 mg/kg per 24 h) into rats every 8th h starting 1 day before transplantation until day 21 or graft loss, or it was injected at a low and clinically relevant dose regimen (45 mg/kg per 24 h) until day 9. CyA was administered orally (10 mg/kg per 24 h) from day 1 through day 9. Ciprofloxacin given alone at a high-dose regimen resulted in a median graft survival of 14.8 days, which was significantly longer than graft survival in rats without treatment (median 8.0 days). A low-dose regimen of ciprofloxacin alone did not affect graft survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

The effects of combined treatment with the novel vitamin D analogue MC 1288 and cyclosporine A on cardiac allograft survival.

The efficacy of combined treatment with the novel vitamin D analogue MC 1288 (20-epi-1 alpha,25-dihydroxycholecalciferol) and cyclosporine A (CyA) in preventing rejection following organ transplantation was evaluated in the heterotopic cardiac allograft model. Wistar/Kyoto rats received hearts from PVG donors and were subsequently treated with MC 1288 and CyA in various dose combinations. Administration of MC 1288 0.1 microgram/kg together with CyA 5 mg/kg produced significantly prolonged graft survival times as compared with single therapy with MC 1288 0.1 microgram/kg (p < 0.01) or CyA 5 mg/kg (p < 0.001). MC 1288 and CyA were tested also in combination with the immunomodulating drug LS-2616, which, in several laboratories, is used as a model for the evaluation of new combinations of immunosuppressive drugs. LS-2616 abolishes the immunosuppressive effect of CyA and the transplanted hearts are thus rejected at the same time as grafts of untreated recipients, i.e. on day 8. The immunosuppressive effect of MC 1288 is also counteracted by LS-2616, but the effect is not absolute and the median graft survival time is 11.0 days. Combined treatment with MC 1288 and CyA in the presence of LS-2616 resulted in a median graft survival time of 14.0 days. The results obtained in our experiments indicate at least an additive effect of MC 1288 and CyA thus suggesting that in the future MC 1288, or other vitamin D analogues, might be used to control rejection, either alone, in combination with CyA or in combination with other immunosuppressive drugs with other mechanisms of action.

Adjuvants, Immunologic↗
PubMed1995

Alterations of the post transplant blood lymphocyte phenotype subsets as a marker of rejection in renal allograft recipients.

The postoperative alterations of absolute levels of lymphocyte phenotype subsets in peripheral blood were studied in recipients of living donor renal allografts and in kidney donors. The results were expressed as per cent changes of the preoperative values. The lymphocyte subsets, CD3, CD4 and CD8 cells, decreased to approximately 50% following the surgical trauma, with rapid recovery to preoperative levels within 1 week in kidney donors and in recipients without rejection episodes. In contrast, the T-cell levels in recipients with rejection episodes remained low after 1 week, before clinical signs of rejection, and was predictive for the later occurrence of acute rejection episodes. The T-cell levels in the recipients with rejection episodes remained low during the first 6 weeks, maybe due to the rejection treatments given during this period. The B-lymphocytes were not affected in any of the recipient groups. The alterations observed were not explained by CMV infections, which occurred mainly after the observation period of 6 weeks. In conclusion, the operation per se induced alterations in circulating T-lymphocyte subsets and low T-cell levels after 1 week were predictive of rejection episodes.

Adult↗
PubMed1995

Evaluation of an organ-donor-card campaign in Sweden.

One of the aims of this study was to evaluate an information campaign carried out in three geographical areas of Sweden in the winter of 1992-93. The campaign was intended to increase public awareness of organ donation and to increase the signing of donor cards. Another objective was to test the effects of different kinds of information. These were: A) an extensive "package" of information including training of key groups, lecturing at meetings and exhibitions, and advertisements of donor cards: B) a brochure to households including two donor cards; and C) a combination of A and B. Yet another aim was to reassess public opinion on transplantation issues, which had been surveyed before in 1987, 1988, and 1990. Random samples of the population in three campaign areas and a control sample were surveyed before and after the campaign, altogether 5600 persons. The average response rate was 69% (1992) and 68% (1993). In the two areas where the brochure had been distributed to the households, the rate of donor card holders had more than doubled (from 3% and 5% to 13% and 12%). In the two areas where the brochure had not been distributed, the rate was unchanged (5%). In the "brochure areas" also a somewhat larger number of people had informed their relatives about their decisions, compared with people in the other areas. In all campaign areas considerably more people were aware of the cards than in the control area. No attitude changes could be shown in any area.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗