MRP8/14-positive macrophages as early acute cellular rejection markers, and soluble MRP8/14 and increased expression of adhesion molecules following renal transplantation.
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Biomedical subjects
Publications and source records attributed to K Burkhardt.
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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.
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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.
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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.
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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.
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.
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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.
The concentrations of active agent were determined in the bile and serum after oral administration of ampicillin and pivampicillin to 12 patients 7-9 days after surgical revision of the common bile duct. Orally, pivampicillin is more rapidly absorbed, maxima of active agent and the mean serum concentrations are higher compared with ampicillin. The rate of absorption and serum concentrations after giving ampicillin and pivampicillin depend on the type of diet. Pivampicillin produces higher concentrations of active agent in the bile of the common bile duct more rapidly than ampicillin. The mean concentration of active substance in the bile is distinctly above the serum concentrations.
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Among a total of 82 children treated conservatively and surgically for hiatal hernia and gastro-esophageal malposition (Lortat-Jacob) 14 cases (17%) of peptic stenosis of the esophagus was observed. In an evaluation of the etiology of peptic esophageal stenosis the importance of anatomical growth and morphological changes of the cardia during infancy is stressed. Analysis of patient data revealed an unusually short period of stenotic manifestation after the first symptoms of reflux had been noted. Fundoplication with or without bouginage on an endless string seems to constitute the most beneficial form of therapy.
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