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G Tufveson

Publications and source records attributed to G Tufveson.

At least 145 records · Page 8Linked to original sources
PubMed1990

The localization of hyaluronan in normal and rejected human kidneys.

Hyaluronan (HYA) is a large glycosaminoglycan with a high capacity to immobilize water. Increased levels of HYA have previously been observed in plasma as well as in affected tissues in various inflammatory conditions. The morphological localization of HYA has, however, not been described in normal or rejected human kidneys. Using a recently developed method for localization of HYA in tissue sections by means of a biotin-labeled hyaluronan binding protein used as a probe, we have now investigated the distribution of HYA in normal and irreversibly rejected human kidneys. In the normal kidney HYA was essentially confined to the medulla. In the rejected kidneys increased amounts of HYA were observed primarily in the cortex and in sclerotic vessels. Incubating tissue sections with hyaluronidase abolished the staining for HYA, showing the specificity of the staining procedure. The increased amounts of HYA of the rejected kidney may play a role in local edema formation, and thereby alter graft function.

Connective Tissue↗
PubMed1990

Rapidly proliferative arteriopathy in cyclosporin-induced permanently surviving rat cardiac allografts simulating chronic vascular rejection.

In an attempt to create a model of chronic rejection in rat, cardiac allograft transplantation was performed of hearts from PVG rats to DA rats treated with cyclosporin, 20 mg/kg body weight per day for 14 days and thereafter no immunosuppressive therapy. Experiments were made in 83 rats fed on a normal diet and in 24 rats fed on a diet containing an additional 0.5% cholesterol. Rats on the normal diet showed moderate signs of acute rejection during the first 20-40 days and grafts were lost in acute rejection during this period of time. However, after 2-3 months no signs of acute rejection were present. On the contrary, excessive proliferative changes of the vascular intima and endocardium along with fibrosis and fibrin deposition appeared and was progressive until 6 months post-transplantation. These morphological changes are similar to those found in chronically rejected organs like heart and kidney. In rats fed on a cholesterol diet after cessation of cyclosporin, development of the vascular and endocardial proliferative changes appeared three to four times as fast and were on average fully developed within 4-6 weeks post cessation of cyclosporin treatment. The recipients' own hearts showed no signs of vascular or endocardial damage. It is thus concluded that two models of vascular and endocardial proliferative changes in cardiac allografts have been developed showing distinct similarities to chronic vascular rejections seen in the clinical transplantation and with apparent similarities to severe arteriosclerosis. The models could be useful in the investigation of pathogenesis and therapeutical means for preventing chronic vascular damage in transplanted organs and arteriosclerosis.

Animals↗
PubMed1990

Immunomorphology of graft-versus-host disease after small bowel transplantation in the rat.

The process of graft-versus-host disease (GVHD) elicited by small bowel semi-syngeneic grafts in Lewis rats was studied by an immunohistochemical staining technique for analysis of MHC (major histocompatibility complex) class II antigen expression and of T-cell subpopulations in different organs. Specimens from the graft, native bowel, brain, testis, liver, kidney, and skin were taken on days 5, 10, and 15. All the investigated organs displayed strong class II antigen induction during the course of GVHD. In the native bowel of semi-syngeneically transplanted animals, only discrete morphological changes were noted, whereas the graft displayed a generalized serosal reaction with large infiltrates of rounded and polygonal cells expressing class II antigens. This was not observed in the graft of syngeneically transplanted animals. In the lamina propria of the semisyngeneic graft, 'free' lymphocyte-like cells were depleted and, at the same time, localized aggregates of these cells were observed. Crypt cell class II expression in the native bowel, and to some extent in the graft, was increased during GVHD. However, pronounced intraindividual variations in MHC class II antigen expression were noted, and class II expression was therefore not considered to be a good marker for GVHD.

Animals↗
PubMed1990

Characteristics of mouse to rat xenograft heart transplantation.

A simple technique for grafting a mouse heart heterotopically to rat neck vessels in experimental xenotransplantation is described. In this series, graft survival was tested with the following modes of immunomodulation: ciclosporin (Cy), athymic and nude rats, splenectomy, total lymphoid irradiation (TLI), 15-deoxyspergualin in two different doses and various combinations of these. The mean graft survival time, with Cy or athymic and nude rats as recipients, was 3 days as also seen in animals without treatment. With either irradiation, splenectomy or 15-deoxyspergualin, 10 mg/kg daily, the graft survival time was prolonged to 7.8, 4.7 and 6.8 days, respectively. In combination, TLI + splenectomy gave a graft survival of 9.7 days and Cy + splenectomy 7.2 days. With 15-deoxyspergualin at 10 mg/kg/day plus splenectomy, done 1 week prior to transplantation, graft survival was extended to 17.8 days.

Animals↗
PubMed1990

Accumulation of hyaluronan (hyaluronic acid) in myocardial interstitial tissue parallels development of transplantation edema in heart allografts in rats.

By using biotin-labeled proteoglycan core protein, hyaluronan (hyaluronic acid; HA) was visualized in rat heart grafts at different times (2, 4, and 6 d) after transplantation. In normal, nontransplanted hearts HA was present in the adventitia of arteries and veins and in the myocardial interstitial tissue. An increased accumulation of HA was evident in the edematous interstitial tissue, infiltrated with lymphocytes, on day 4 after allogeneic transplantation, and was even more pronounced by day 6. No apparent increase in HA was seen in syngeneic grafts. Biochemical assay of HA in heart tissue demonstrated that the myocardial content of HA had increased 60% by day 2 after transplantation in allogeneic as well as syngeneic grafts, indicating that surgical trauma may induce some HA accumulation in heart grafts. The extractable amount of HA declined during the following days in the syngeneic grafts, but increased progressively during the development of rejection in the allogeneic grafts, and increased on average three times by day 6. The relative water content also increased progressively during rejection of allogeneic grafts and correlated with the HA accumulation. The interstitial accumulation of HA, a glycosaminoglycan with unique water-binding qualities, is presumably implicated in the development of interstitial edema during rejection of heart grafts.

Animals↗
PubMed1990

Influence of the age of cadaveric kidney donors on transplantation outcome and rate of surgical complications.

Cadaveric kidney graft recipients, treated according to a strict, high dose CyA protocol, were followed prospectively for one year. The aim was to study the impact of donor age on transplantation outcome in a homogenously immunosuppressed patient material. The patients were divided into 2 groups; G1: donor age less than or equal to 50 years (mean 34.5 y; range 10-50; n = 49) and G2; donor age greater than 50 years (mean 58.1 y; range 51-68; n = 37). The groups were comparable in terms of recipient age, warm and cold ischemia time, number of HLA A, B, DR mismatches and number of rejection episodes. The result showed no difference in mortality between the 2 groups (12% vs. 13%). One year graft survival was 70% vs. 51% (NS), immediate onset of function was 76% vs. 46% (p less than 0.01), creatinine concentration at one year was 146 +/- 39 vs. 206 +/- 73 mumol/l (p less than 0.05) for G1 and G2, respectively. The most striking finding was a highly significant difference in the rate of graft-related surgical complications, 12% vs. 35% (p less than 0.01) for G1 and G2, respectively. We conclude, that a patient receiving a graft from an elderly donor, runs a higher risk of graft-related complications and that long term graft survival and function also might be influenced by the age of the donor. A possible reason for the inferior results in group 2 might be an increased sensitivity for the toxic effects of CyA of aging kidneys.

Adult↗
PubMed1989

Influence of different preservation solutions and intentional hemodilution of recipient on viability of preserved and transplanted rat kidneys.

A total of 81 rat kidney grafts, flushed out and cold stored in either Sacks' or University of Wisconsin (UW) solution, were transplanted into hemodiluted (Hct = 30% +/- 4%) or untreated (Hct = 43% +/- 3%) recipients. The cold ischemia times (CIT) used were 24 and 36 h. One week after transplantation, the surviving recipients (n = 67) were contralaterally nephrectomized. The experiment was terminated after a total period of 4 weeks, and the percentage of surviving animals was determined for each treatment. Data was pooled and the results show that grafts cold stored in UW solution were viable to a significantly greater extent and after longer CIT than grafts cold stored in Sacks' solution (47% vs 23%; P less than 0.05). Recipient hemodilution did not improve graft viability (39% vs 32%; NS). Kidneys cold stored for 24 h were viable to a greater extent than kidneys with a CIT of 36 h (50% vs 15%; P less than 0.01).

Animals↗
PubMed1989

Contribution of toxic nephropathies to end-stage renal failure in Europe: a report from the EDTA-ERA registry.

In countries which reported to the registry of the European Dialysis and Transplant Association (EDTA)-European Renal Association, 2.4% of 147 092 treated patients were recognized as having analgesic nephropathy (AN) as the cause of end-stage renal failure (ESRF) on 31 December 1986. A small number of patients had other specific drug nephropathies, but these do not yet make an important contribution to ESRF treatment programmes. It is possible that more patients have ESRF due to AN, and evidence from studies of age distribution, the demography of urothelial malignancies, a special study of diagnostic criteria, data on sales of analgesics, and a study of regional areas of high incidence lend some support to that view. Changes in prescription and self-medication practices over the last 20 years have almost eradicated analgesic nephropathy from the U.K. and Sweden, two countries in which there was previously a high frequency of ESRF due to AN. In other countries where action has been taken more recently, cases are still reported fairly frequently, and this seems likely to continue for several years to come.

Adolescent↗
PubMed1989

Platelet-derived growth factor receptors in the kidney--upregulated expression in inflammation.

Major features of a long-standing inflammation in the kidney are vascular proliferation, glomerulosclerosis, interstitial fibrosis and tubular atrophy, leading to a gradual deterioration of the renal function. In this study we have investigated the expression of B-type receptors for platelet-derived growth factor (PDGF) in frozen sections from normal and inflamed kidneys. Immunohistochemical techniques, employing two monoclonal antibodies specific for PDGF B-type receptors, were used. The specimens investigated were 15 kidneys removed by transplantectomy because of chronic rejection, 20 cases of glomerulonephritis with crescent formation, mesangial proliferation or non-proliferative glomerulonephritis, and six normal kidneys. In parallel we characterized cellular infiltrates and class II transplantation antigen expression in the inflamed kidneys. An enhanced PDGF receptor expression was found on intimal cells and on smooth muscle cells of the proliferating vessels, on glomerular cells in glomeruli with mesangial proliferation, and on fibroblast-like cells in the proximity of clusters of infiltrating macrophages and T-lymphocytes of the interstitial tissue. Induction of PDGF receptor expression may render cells responsive to stimulation by PDGF, released from PDGF-producing cells, such as activated macrophages and from platelets. Our data suggest that PDGF is involved in the proliferation of mesenchymal cells that is seen in rejected kidney transplants and glomerulonephritis.

Antibodies, Monoclonal↗
PubMed1989

Circulating T-lymphocyte sub-subsets and NK-like cells in renal transplant patients: patterns associated with rejection.

The patterns of circulating T sub-subset and NK-like cells were monitored in 87 renal transplant patients on a total of 122 occasions. Combinations of monoclonal antibodies were used in two-colour flow cytometric (FACS) analysis to define the major T helper/inducer and T suppressor/cytotoxic subsets and their activated counterparts, the T suppressor inducer and T suppressor effector sub-subsets, NK-like cells and their activated counterparts. In patients with rejection, the proportions of T suppressor inducer and T suppressor effector cells were less and the proportion of activated NK-like cells greater compared with cases exhibiting stable graft function, and these group differences were highly significant. Analysis with stepwise multivariate logistic regression showed that combinations of several functional/activated lymphocyte subsets allow a predictive diagnostic power which is superior to the use of single variables.

Antibodies, Monoclonal↗
PubMed1989

EDTA Registry centre survey, 1986. Report from the European Dialysis and Transplant Association Registry.

This paper summarises the information given on the 1986 EDTA Registry centre questionnaire which was returned by 82% of the 2,065 known dialysis and transplant centres in 33 European countries. Information is given on the number of patients alive on haemodialysis according to the type of dialysis facilities available where the patient was receiving dialysis and the number of patients receiving special types of dialysis. The centre questionnaire also included questions on testing for HIV infection, serological evidence or symptoms of AIDS and the diagnosis of hepatitis B in patients and staff. The data given in response to these questions are presented together with data on the involvement of dietitians and social workers in the treatment of patients with end stage renal failure. Finally, information on transplant activity in Europe and the treatment policies of transplanting centres is provided.

AIDS Serodiagnosis↗
PubMed1989

Abolition of the effect of cyclosporine on rat cardiac allograft rejection by the new immunomodulator LS-2616 (Linomide).

The effect of the quinoline-3-carboxamide LS-2616 (Linomide), given alone or together with cyclosporine, was studied in the first set cardiac allograft transplantation model in the rat. PVG rat hearts were transplanted heterotopically to Wistar/Kyoto rat recipients on day 0. The recipients were given LS-2616 orally on day -1 to rejection and/or CsA orally on days 0-9. In untreated animals rejection occurred on days 8-9, as judged by the absence of palpable pulsations. Treatment with CsA (5 or 10 mg/kg) resulted in prolongation of graft survival to days 17-21, i.e., the rejection occurred 8-10 days after cessation of treatment. LS-2616 in a dose of 160 mg/kg did not in itself have any impact on graft survival, but when given in doses of 40 or 160 mg/kg simultaneously with CsA (10 mg/kg), the effect of CsA was totally abolished. Animals treated with LS-2616 together with CsA had slightly lower trough blood levels than those treated with CsA alone. This interaction with CsA pharmacokinetics does not explain the results, as doubling of the CsA dose to 20 mg/kg, which well compensated for the difference in blood levels, was not sufficient to reverse the effect of LS-2616. To our knowledge this is the first compound known to abolish the effect of CsA. The mechanism is unknown, but is is possible that studies on the interaction between these two drugs will shed further light on the molecular basis of their modes of action.

Adjuvants, Immunologic↗
PubMed1989

Immunologic diagnosis of kidney rejection using FACS analysis of graft-infiltrating functional and activated T and NK cell subsets.

In human organ transplantation, the correct diagnosis of rejection may be difficult using clinical and/or histopathologic criteria, and immunologic assays should therefore be considered. We have applied monoclonal antibodies in 2-color flow cytometric (FACS) analysis to study phenotypic patterns of kidney-infiltrating activated and functional T and NK cell subsets in 132 posttransplantation biopsies. Viable intragraft lymphocytes and kidney tubular cells were obtained by the use of medium-sized ultra-sound guided needle biopsy. In univariate analyses, highly significant differences were observed between rejecting and stable grafts. During rejection, the proportions of HLA-DR+ kidney tubular cells, total lymphocytes, T suppressor/cytotoxic cells, and natural killer (NK)-like cells increased; the fractions of phenotypically activated, HLA-DR+ cells within the latter 2 cell populations were elevated. Further, during rejection phenotypic T suppressor inducer and T suppressor effector cells were virtually absent in kidney tissue but reappeared rapidly upon successful antirejection therapy. Multivariate analyses revealed that combinations of antibodies in FACS analysis defining functional and activated subsubsets of T and NK cells allow a precise and rapid immunologic diagnosis of kidney rejection.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

The effect of type of preservation solution and hemodilution of the recipient on postischemic erythrocyte trapping in kidney grafts. An experimental study in the rat.

The role of recipient hemodilution for postischemic renal medullary red cell trapping was investigated after different periods of cold storage in a conventional cold storage solution (Sacks'). At all cold storage times investigated (4, 12, 24, and 48 hr) medullary red cell trapping was reduced by isovolemic hemodilution, with about 50% reduction of recipient hematocrit. Trapping was also reduced when a modification of a new preservation solution (University of Wisconsin solution [UW]) was used and compared with flush-out and storage in a standard preservation solution (Sacks'). The combination of hemodilution and preservation in modified UW solution had additional capacity to reduce medullary red cell trapping. Thus, even after 48 hr of cold storage, only a moderate trapping was observed. The results also indicate that measurements of medullary red cell trapping offers an accurate method of grading postischemic renal damage.

Adenosine↗
PubMed1989

Relevance of additive components of University of Wisconsin cold-storage solution. An experimental study in the rat.

The purpose of this study was to evaluate the value of additive components and colloid included in the University of Wisconsin (UW) solution. Therefore, this solution was compared with a solution consisting of the basic components of the UW solution (potassium lactobionate, raffinose, phosphate buffer and MgSO4). We employed a method of measuring the amount of chromium-51-labeled erythrocyte trapped in the medullary vasculature 20 min after reperfusion of kidney grafts cold-stored for 24-48 h in either the basic UW (bUW) or the original UW (oUW) solution. The amount of trapping has been shown to correlate well with the degree of cold ischemic injury. Both hemodiluted (hct 20-27%) and normal (hct 41-45%) recipients were used. Long-term viability of grafts stored in either bUW or oUW was investigated in survival experiments and the flow rates during in situ flush-out were also measured, as well as weight changes during the storage period. The results showed no significant difference between the two solutions, regardless of ischemia time or whether hemodiluted or normal recipients were used. However, the flow rate and weight measurements showed that flushing was more rapid and kidney swelling less pronounced using oUW. Survival rates in long-term transplantation experiments were similar. It was concluded that the inclusion of a colloid improves the rheological properties of the UW solution and that the additives besides the basic components did not offer any advantage.

Animals↗