| 1. |
- Wanders, A., et al.
(author)
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Effect of LS-2616 on the graft protection achieved by cyclosporin A, prednisolone, and 15-deoxyspergualin in heart-transplanted rats
- 1992
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In: Transpl Int. ; 5 Suppl 1, s. S462-3
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Journal article (peer-reviewed)abstract
- The immunostimulator LS-2616 abolishes the effect of cyclosporin A in a rat cardiac transplantation model. The present paper compares the characteristics of rejection obtained under different immunosuppressive regimens with and without additional LS-2616 application in the same model. Cyclosporin A (CyA, 10 mg/kg daily), prednisolone (15 mg/kg daily), or 15-deoxyspergualin (2, 5, or 10 mg/kg daily), all given from the day of transplantation until day 9, protected the grafts during the treatment period. The addition of LS-2616 (160 mg/kg, day -1 until stop) resulted in a total abrogation of the immunosuppressive effect of CyA and prednisolone. However, LS-2616 could only partially or not at all reverse the effect of 15-deoxyspergualine. These results show a certain drug selectivity of LS-2616 in promoting rejection of immunosuppressed allografts. Further studies with LS-2616 may be of benefit in evaluating the mode of action of different immunosuppressive compounds and, thus, contribute to finding more effective antirejection therapies.
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| 2. |
- Wanders, A., et al.
(author)
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Effects of prostaglandin E2 (PGE2) and drugs affecting PGE2 degradation on acute rejection of rat cardiac allografts
- 1992
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In: Scand J Thorac Cardiovasc Surg. ; 26:1, s. 33-7
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Journal article (peer-reviewed)abstract
- Systemic administration of prostaglandin E2 (PgE2) has been reported to prolong graft survival of heart transplants. We investigated the influence of systemic injection of two compounds which inhibit the endogenous degradation of PgE2 (CL42A and CL68A) and of local infusion of PgE2 into the transplant on the survival time of rat cardiac allografts. Both CL42A and CL68A gave increased graft survival time in two rat strain combinations, though this was not predictable in individual rats. Locally infused PgE2 gave slight, but not significant prolongation of graft survival in some recipients. Combined PgE2 and cyclosporin A, however, gave significant prolongation of graft survival time compared with cyclosporin A treatment alone. When local PgE2 treatment was begun 5 days after transplantation, graft survival time was prolonged in almost all the rats. Manipulation of the local PgE2 concentration thus seemed to have a positive effect on graft survival, possibly due to down-regulation of certain cells of the immune system by PgE2.
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| 3. |
- Wanders, A., et al.
(author)
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Evidence that LS-2616 (linomide) causes acute rejection of rat allografts protected by cyclosporine but not of long-term surviving allografts
- 1991
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In: Transplantation. - 0041-1337 .- 1534-6080. ; 52:2, s. 234-8
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Journal article (peer-reviewed)abstract
- The immunomodulator LS-2616 (Linomide) induces rejection of cyclosporine-protected rat cardiac allografts. The aim of this study was to characterize this rejection in the presence of CsA and to test LS-2616 in other models of permanent graft acceptance in the rat. PVG rat hearts were transplanted heterotopically to Wistar/Kyoto (Wi/Ky) rat recipients on day 0. The recipients were treated orally on days 0-9 with CsA (10-40 mg/kg) and/or with LS-2616 (2.5-160 mg/kg) starting at different times (day -7 -+5) until the day of complete rejection. The addition of LS-2616 (day -1--stop) to CsA (10 mg/kg) resulted in a dose-dependent antagonism of the immunosuppressive effect of CsA with daily doses of 2.5-160 mg/kg. Furthermore, the results were similar, irrespective of whether LS-2616 treatment (160 mg/kg) was started on day -7, -1, +1, +3, or +5. LS-2616 (160 mg/kg) pretreatment of the recipient for 7 days before transplantation was considerably less effective. CsA (20 mg/kg) for 14 days after a PVG to DA transplantation resulted in permanent graft survival. This was not abrogated by LS-2616. Neither was rejection induced in long-term surviving grafts of RT1.C incompatible Lewis recipients. Our data suggest that LS-2616 activates already stimulated and sensitized T cells that are otherwise controlled by CsA.
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| 4. |
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| 5. |
- Ahrenstedt, O, et al.
(author)
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Increased luminal release of hyaluronan in uninvolved jejunum in active Crohn's disease but not in inactive disease or in relatives.
- 1992
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In: Digestion. - 0012-2823 .- 1421-9867. ; 52:1, s. 6-12
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Journal article (peer-reviewed)abstract
- Recently obtained data suggest that there is a subclinic inflammatory activity in the apparently uninvolved intestinal mucosa in Crohn's disease (CD). As CD is characterized by an activation of connective tissue and fibrosis, we investigated the extent to which hyaluronan (HA), an essential component of the connective tissue, was released into the lumen of an isolated jejunal segment in CD patients and in relatives. Patients with active CD of the terminal ileum (CD activity index, CDAI, > 150; n = 14), patients with CD in remission (CDAI < 150 n = 10), first-degree relatives of the CD patients (n = 21) and healthy controls (n = 43) were orally intubated with a catheter allowing occlusion and perfusion of a segment of the proximal jejunum. The jejunal fluid concentration of HA was 65 +/- 45 micrograms/l in patients with active CD in the terminal ileum, significantly higher than the value for 43 healthy controls (42 +/- 23 micrograms/l; p < 0.05), and the corresponding values for patients in remission (42 +/- 23 micrograms/l) and for first-degree relatives of the CD patients (53 +/- 52 micrograms/l), were not increased compared to the control group. To localize HA in the tissue, small bowel biopsies were taken during surgery from patients with CD and from controls and affinity stained for HA. There was an intense staining for HA in the lamina propria of the villi, both in biopsies from patients with CD and from controls, but no staining in the epithelium.(ABSTRACT TRUNCATED AT 250 WORDS)
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| 6. |
- Farzad, A, et al.
(author)
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Luminal release of hyaluronan (hyaluronic acid) in intestinal ischemia in the rat.
- 1993
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In: Digestion. - 0012-2823 .- 1421-9867. ; 54:3, s. 168-72
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Journal article (peer-reviewed)abstract
- Hyaluronan (HA) is a glycosaminoglycan, the water-binding properties of which are suggested to be pivotal for an optimal hydration of tissues. The lamina propria of the intestinal villi is characterized by a high concentration of HA. Increased amounts of HA are observed in the intestinal lumen in patients with Crohn's disease. We have evaluated whether epithelial denudation as such is sufficient to increase the concentration of HA in the lumen of the small intestine. Epithelial damage was accomplished by reversible ischemia-reperfusion injury to the rat ileum and the concentration of HA was determined in luminal perfusate. The perfusate concentration of HA was increased from 26 +/- 8 micrograms/l before ischemia, to 68 +/- 13 and 41 +/- 12 micrograms/l 0-30 and 30-60 min after a 60-min period of subtotal ischemia without venous stasis (p < 0.05). In sham-operated animals, in contrast, the perfusate concentration of HA was virtually unchanged (31 +/- 18, 13 +/- 3 and 10 +/- 1 microgram/l, respectively). Specific staining for HA on sections revealed loss of HA from the villus tips after ischemia. The results show that epithelial denudation results in loss of HA from the villus interstitium to the intestinal lumen.
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| 7. |
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| 8. |
- Gerdin, Bengt, 1947-, et al.
(author)
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Localisation of hyaluronan in the human intestinal wall.
- 1991
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In: Gut. - 0017-5749 .- 1468-3288. ; 32:7, s. 760-2
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Journal article (peer-reviewed)abstract
- By using biotin labelled proteoglycan core protein and an avidin enzyme system, hyaluronan (hyaluronic acid) was visualised in specimens of human jejunum. Intense staining for hyaluronan was seen in the loose connective tissue of the villi and of lamina propria while the epithelial layer was unstained. The muscularis mucosae showed only faint staining. The accumulation of hyaluronan in the subepithelial layer of the jejunal mucosa indicates that the previously reported high jejunal secretion of hyaluronan is due to passive diffusion from the subepithelial interstitium. The physicochemical characteristics conferred by hyaluronan may be important for the villi function.
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| 9. |
- Gerdin, E, et al.
(author)
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Immunohistochemical identification of receptors for epidermal growth factor in tumor endothelium may be affected by cross-reactivity to blood group A antigen.
- 1993
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In: American Journal of Clinical Pathology. - 0002-9173 .- 1943-7722. ; 99:1, s. 28-31
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Journal article (peer-reviewed)abstract
- It has been reported that endothelium in malignant glioma stains with a commercial antibody raised against the receptor for epidermal growth factor (EGFr) on A431 cells (clone 29.1). In this report, this antibody was used to study the immunohistochemical expression of EGFr in benign and malignant ovarian, mid-gut carcinoid, and thyroid neoplasms using the avidin-biotin-peroxidase complex technique. Eighteen of the 37 ovarian neoplasms, 4 of the 10 thyroid neoplasms, and 14 of 28 mid-gut carcinoid tumors expressed strong and distinct endothelial staining, whereas staining results of the remaining tumors were negative. The endothelial nature of the staining was verified by staining serial sections with Ulex europaeus agglutinin-I. The staining was independent of that obtained with an antibody raised against a synthetic peptide consisting of residues 985 to 996 from the cytoplasmic domain of EGFr (clone F4). All positive staining occurred in patients determined to be of blood groups A or AB, whereas samples from patients with blood groups B or O were negative. Immunoabsorption of the antibody with centrifuged erythrocytes from a blood group A donor, but not from a blood group B donor, abolished the positive staining. The data indicate that positive staining of tumor endothelium with this antibody is due to cross-reactivity with blood group A antigen. The results obtained challenge the validity of previously performed immunohistochemical studies in which monoclonal antibodies raised against the EGFr of A431 cells have been used, and in which the epitope for the monoclonal antibody has not been determined.
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| 10. |
- Graf, W, et al.
(author)
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Delorme's operation for rectal prolapse in elderly or unfit patients.
- 1992
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In: European Journal of Surgery. - 1102-4151 .- 1741-9271. ; 158:10, s. 555-7
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To evaluate the results after Delorme's operation for rectal prolapse in elderly and unfit patients.DESIGN: Retrospective analysis and telephone interview.SETTING: Akademiska sjukhuset, Uppsala, Sweden.SUBJECTS: A consecutive series of 14 women (median age 82, range 32-92) operated on for rectal prolapse 1987-1992 and followed up after a median of 18 months.RESULTS: There were no serious postoperative complications. Continence was improved in 6/11 incontinent patients. The recurrence rate was 3/14 (21%).CONCLUSION: Delorme's operation is an attractive alternative in elderly or unfit patients, but is not recommended for younger and low risk patients because of the recurrence rate.
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