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K Burkhardt

Publications and source records attributed to K Burkhardt.

At least 37 records · Page 2Linked to original sources
PubMed1994

Production of proinflammatory cytokines and adhesion molecules in ex-vivo xenogeneic kidney perfusion.

Xenogeneic transplantation of solid organs is limited due to hyperacute rejection. In concordant systems, the mechanisms of rejection can be studied due to cross-reactivity of mediators with anti-human monoclonal antibodies. The aim of this study was to obtain information about the kinetics of proinflammatory cytokines and production of soluble adhesion molecules in the acute phase of reperfusion, eight kidneys from rhesus monkeys were perfused ex-vivo with human blood (group B/0) for 1 hour in a closed system. Blood levels of IL-1b, IL-6, TNFalpha, soluble ICAM, and E-selectin were measured using an ELISA technique under steady-state conditions. Cytokine levels rose significantly within the 60-min interval (IL-1b, 6.1 +/- 2.6-161.1 +/- 98.5 pg/ml; IL-6, 30.2 +/- 7.7-274.2 +/- 75.8 pg/ml; TNFalpha, 544.2 +/- 363.6-1651.0 +/- 25.7 pg/ml; P < 0.05). Immediately after the beginning of reperfusion, soluble ICAM-1 and selectin levels were abnormally high and rose constantly throughout the observation period, reaching significance at 60 min. High levels of proinflammatory cytokines may lead to an induction of adhesion molecules, thus, upregulating the leukocyte-endothelial interaction in a complement-independent mechanism. Specific pretreatment with monoclonal antibodies against ICAM-1, LFA-1, or other soluble mediators may be useful in down-regulating hyperacute rejection in trans-species transplantation.

Animals↗
PubMed1993

Capillary deposition of C4d complement fragment and early renal graft loss.

Clinical outcome of kidney grafts that are affected by the complex syndrome of 'early graft dysfunction' is uncertain and rather unpredictable. In this study, an individual prognosis for dysfunctioning allografts (N = 93) is attempted by the immunohistological assessment of vascular classical complement activation in graft biopsies. Thus, capillary deposition of complement fragment C4d was observed in the majority (N = 51) of early dysfunctioning grafts. In 43 biopsies, abundant deposition of fragment C4d was present in all capillaries, whereas in eight specimens a segmental distribution of capillary C4d was observed. In 42 grafts with early dysfunction no capillary C4d was detectable. Eighteen subsequent graft losses within one year (16 early losses) were recorded in the subgroup with C4d in all capillaries, and three early losses in the group with segmentally distributed C4d. Only four graft losses (3 early losses) were recorded in the C4d-negative group (P = 0.0027; Pearson's chi square test). The resulting one-year graft survival rates (72% for the study group) differed markedly between the subgroups. Grafts with generalized or segmental capillary deposition of C4d had 57% and 63% survival, respectively, contrasted by 90% survival in the C4d-negative group. It is of note, however, that also three of the four grafts that were finally lost within the C4d-negative group, showed distinct capillary deposition of C4d in second biopsies. Vascular deposition of complement fragment C4d therefore represents a clinically relevant factor that contributes to early graft dysfunction. Its assessment is helpful for an individual graft prognosis.

Animals↗
PubMed1993

Distribution of cell adhesion molecules (ICAM-1, VCAM-1, ELAM-1) in renal tissue during allograft rejection.

The tissue distribution of cellular adhesion molecules (CAMs) was studied in specimens from 10 normal human kidneys and in 52 biopsies from kidney allografts with cell-mediated rejection. In addition to the vascular presence of ICAM-1, a common finding in normal kidneys, expression of ICAM-1 on tubular cells was observed in 22 graft biopsies. Compared with normal kidneys, where VCAM-1 was present on Bowman's capsules and few proximal tubular cells, a markedly enhanced expression of VCAM-1 in numerous tubuli (including distal tubular segments) was observed in 51 graft biopsies. In 41 graft specimens VCAM-1 appeared also in variable numbers of peritubular capillaries. Infiltrating leukocytes carrying VCAM-1 were observed in 7 grafts. ELAM-1 could not be found in normal kidneys but was restricted to some peritubular capillaries in 29 grafts. Comparable results were obtained with cultured renal tubular cells when stimulated by TNF-alpha. That the induced appearance of adhesion molecules was in fact related to actual cellular synthesis was demonstrated by Northern blot analysis. Thus, little ICAM-1 specific mRNA of 3.4-kb length could be detected in unstimulated cultured renal tubular cells, but hybridization was markedly increased after stimulation with TNF-alpha. A substantial amount of VCAM-1 specific mRNA of 3.2-kb length was present already in unstimulated renal tubular cells. Likewise, synthesis of VCAM-1 mRNA was enhanced by stimulation with TNF-alpha. TNF-stimulated endothelial cells also showed weak synthesis of VCAM-1 mRNA. The results provide further evidence that constitutive and inducible expression of cell adhesion molecules contributes to the process of allograft rejection.

Antibodies, Monoclonal↗
PubMed1989

An increase in the survival of murine H-2-mismatched cultured fetal pancreas allografts using depleting or nondepleting anti-CD4 monoclonal antibodies, and a further increase with the addition of cyclosporine.

Depletion of CD4+ T lymphocytes with monoclonal antibodies (mAbs) has been shown to prolong allograft survival in mice. In this study, two rat anti-CD4 mAbs, H129.19 and GK1.5, were administered either alone or in combination with cyclosporine (CsA) to recipients of MHC-mismatched (H-2k to H-2d) cultured fetal pancreas allografts to determine their effect on graft survival. When compared with control mice, splenic CD4+ cells of GK1.5-treated mice were depleted by greater than 95%, but in H129.19-treated mice no depletion of CD4+ cells occurred. Instead, rat Ig was present on the surface of CD4+ cells in H129.19-treated mice. Anti-CD4 therapy with either H129.19 or GK1.5 prolonged fetal pancreas allograft survival to a similar extent, but did not lead to indefinite survival. Blockade of the CD4 antigen by the mAb H129.19 was as effective as the depletion of CD4+ cells by GK1.5 in prolonging allograft survival. Rejection of grafts by day 28 posttransplantation occurred in the absence of CD4+ cells, as determined by both flow cytometric examination of spleen cells and immunoperoxidase staining of the graft site. CsA alone did not prolong graft survival, but its addition to either H129.19 or GK1.5 mAb treatment significantly increased the survival rate of grafts at 28 days compared with mAb treatment alone. These results suggest that CD4+ cell depletion is not essential for effective anti-CD4 mAb therapy--and, further, that CsA may have a direct inhibitory effect on CD8+ cells during allograft rejection.

Animals↗
PubMed1989

Anti-IL-2 receptor monoclonal antibody AMT-13 increases soluble IL-2 receptor levels in vivo.

A rat anti-interleukin-2 receptor (IL-2R) monoclonal antibody (mAb), AMT-13, has been shown to prolong cardiac allograft survival in mice. However, neither the mechanism of its immunosuppressive action, nor its other in vivo effects, have been studied extensively. We investigated the effect of AMT-13 on serum-soluble IL-2R levels by a quantitative ELISA technique. Following administration of multiple doses of AMT-13, sufficient to delay fetal pancreatic graft rejection, a rapid and lasting increase in soluble(s) IL-2R levels of up to 20-fold was observed. Levels returned to normal by Day 9 despite continued AMT-13 administration. A similar though less marked increase was observed following a single injection of AMT-13. Irradiation with 350 rads decreased sIL-2R levels, whilst rat Ig-treated control mice had sIL-2R levels within the normal range. In vivo administration of recombinant IL-2 also increased sIL-2R levels, but the effect was transient and slight. No effect on either the release of sIL-2R or expression of cell surface-associated IL-2 receptors was noted when splenocytes were cultured in the presence of AMT-13. We speculate that the increased concentration of sIL-2R in the serum of AMT-13-treated mice may play a role in the immunosuppressive action of this mAb.

Animals↗
PubMed1988

Immunosuppressive effect of the anti-IL-2-receptor monoclonal antibody, AMT-13, on organ-cultured fetal pancreas allograft survival.

Recently, prolongation of cardiac allograft survival in mice was reported using a rat anti-IL-2R mAb (AMT-13). However, its immunosuppressive action in vivo, alone and in combination with other immunosuppressants, and its effect on other organ transplants has not been extensively studied. We grafted cultured fetal pancreas from CBA (H-2k) donors to Balb/c (H-2d) mice. Recipients were treated with 10 consecutive daily injections each of 20 micrograms AMT-13 only, or with an additional mild immunosuppression of 350 rads irradiation. Control groups received rat immunoglobulin or 350 rads irradiation. Graft survival and the phenotype of infiltrating cells were assessed histologically and immunocytochemically on days 12, 17, and 21, and soluble IL-2R levels were measured in the serum with a quantitative ELISA in all recipients. Two of five grafts in the AMT-13-treated group had islets on day 12 posttransplantation despite lymphocytic infiltration in all grafts, while at this time all grafts of rat Ig treated control mice were completely rejected with only scar tissue and a few lymphocytes remaining. Additional immunosuppression with 350 rads irradiation had a marked additive effect with AMT-13. Soluble IL-2R levels in the serum of untreated recipients were not elevated compared with normal serum levels, but recipients injected with AMT-13 had multifold increased soluble IL-2R levels. The percentage of IL-2R+ cells in the grafts of AMT-13-treated animals was either normal (less than 5%) or increased (20%) in the additionally irradiated mice, providing strong evidence that the immunosuppressive effect of AMT-13 is not due to a depletion of activated IL-2R+ lymphocytes.

Animals↗
PubMed1977

[Treatment of postoperative gastrointestinal fistulas by long-term parenteral feeding].

Twenty-nine anastomotic leakages of the gastrointestinal tract were treated by long-term parenteral nutrition; 20 closed spontaneously, the lethality was 18.3%. Especially, well-drained fistulas of the distal small bowel and the colon show a tendency to closure and should be treated by long-term parenteral hyperalimentation (2500-4000 KCal/24 h), if no signs of ileus or diffuse peritonitis are apparent. The technique and chance for success of hyperalimentation are discussed.

Gastric Fistula↗
PubMed1976

[Pathogenesis and clinics of gastric stump carcinoma (author's transl)].

Statistics of postmortem examinations and retrospective long-term observations indicate a disposition of the resected stomach for the development of a primary carcinoma. The risk to develop a carcinoma after resection for peptic ulcer shows a two- to three-fold increase compared to gastric cancer mortality of the normal population. Because of the lack of typical symptoms for gastric stump cancer surgical treatment will occur late and the 5-years survival rate is only 1.38%. The cause of the increased cancer risk after gastric resection seems to be the atrophic gastritis in the gastric remnant which is found after a few years.

Amputation Stumps↗
PubMed1976

[Therapy and prognosis of cardia carcinoma. Study on 225 cases].

From 1955 to 1974, 225 patients with cardia carcinoma were treated at the Department of Surgery in the University of Göttingen. The resection rate was 46,6%. Only 35 of our 105 patients who underwent resection, were operated on radically; in all other patients a palliative resection was done. In 59% of the resection cases a abdominothoracic approach was performed, whereas in 21% an abdominal, and in 20% a thoracic approach was preferred. The abdominal approach seems to be less effective, since a radical operation in most cases was not guaranteed. In 62% of the resected cases, postoperative complications occurred, mainly of pulmonal origin. The postoperative lethality was 18.1%. The prognosis depends on the degree of tumor metastases. The mean survival rate of the radically operated patients was 36.2 months, compared to 9.7 months of the palliatively resected cases. The 5-year survival rate of the resected patients was 12.2%. An improvement of the results can only be achieved by increasing the resection rate and earlier detection of the tumors.

Adult↗