[Fluspirilene--safe weekly tranquilizer?].
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Adult↗
Biomedical subjects
M Wöhrle
Publications and source records attributed to M Wöhrle.
Comparison of the survival of fresh or cultured pancreatic islets, pseudoislets and single cells following allotransplantation beneath the kidney capsule in non-immunosuppressed diabetic rats.
The purpose of the present study was to examine the effect of culture pretreatment and islet structure on transplantation survival time. Donors for islet isolation were highly inbred male Lewis rats (RT 1(1)). Production of single cells was performed by using EDTA and Trypsin. Pseudo-islets were produced by culturing single cell suspensions at 37 degrees C for 12-14 days. Recipients were BDE rats (RT 1u), made diabetic by streptozotocin injection. 1000-1200 islets (or corresponding amount of single cells or pseudoislets) were transplanted to the subcapsular renal space. Five groups were transplanted. Group 1 (n = 5) received freshly isolated islets of Langerhans. Group 2 (n = 7) received single cells, produced from freshly isolated islets. In group III (n = 7) pseudoislets were transplanted. The animals of group IV received 37 degrees C cultured islets (12-14 days), while group V received single cells consisting of 12-14 day cultured islets at 37 degrees C. The median survival times were: gr. I 7 d.; gr. II 5 d.; gr. III 120 d.; gr. IV 11 d.; gr. V 9 d.. Group III showed a prolongation of allograft survival that was statistically significant compared to all other groups. 4 from 7 animals showed a long-term acceptance. It can be concluded that neither culturing islets at 37 degrees C nor producing single cells achieves long-term acceptance. Transplanting pseudoislets resulted in a long-term acceptance of allograft, without immunosuppression of the host. Three factors may be responsible for this success: Firstly, a reduced number of class-II-antigen positive cells, secondly, metabolic state of rest, and thirdly, the transplantation site.
Animals↗
Pancreatic islet xenografts at two different transplantation sites (renal subcapsular versus intraportal): comparison of graft survival and morphology.
Our primary objective in this study was to determine the effect of two different transplantation sites (renal capsule vs. portal vein) on islet xenograft survival and graft morphology. 59 chemically induced diabetic C57BL/6J mice were transplanted either intraportally (n = 30) or under the left renal capsule (n = 29) receiving 300-350 either freshly isolated or culture pretreated (37 degrees C or 22 degrees C) Lewis rat islets without any immunosuppressive therapy. Histology was performed by immunohistochemical staining to examine the morphologic pattern after rejection or after post-transplant normoglycemia for more than 120 days. Life table analysis revealed a significant (p < 0.001) prolongation of xenograft survival using the renal capsule as transplantation site. 75% graft rejection occurred 56 days after transplantation when the renal capsule was used, compared to 19.5 days intraportal. The intriguing finding was that graft morphology was different depending on the transplantation site. After transplantation under the renal capsule we observed predominantly a more periinsular infiltration with focal aggregates of mononuclear cells at the periphery of the graft. This pattern was more consistent with a non-destructive type of insulitis. In contrast, we found direct infiltration of the transplanted islets following intraportal transplantation reflecting a more destructive type of insulitis. In summary, we could demonstrate a significant prolongation of islet xenograft survival by using the renal capsule as transplantation site in contrast to intraportal transplantation. The morphological pattern possibly indicates two different mechanisms of rejection depending on the transplantation site.
Animals↗
Production of purified alginates suitable for use in immunoisolated transplantation.
Alginate is used as a matrix for immunoisolation of cells and tissues in vivo. We have demonstrated previously that commercial alginates contain various fractions of mitogenic impurities and that they can be removed by free flow electrophoresis. The use of purified material is a necessity in order to reveal the parameters that control biocompatibility of the implanted material (such as stability, size, surface charge and curvature, etc.). In this study, we present a protocol for the chemical purification of alginates on a large-scale. Beads made from alginates purified by this multi-step chemical extraction procedure did not induce a significant foreign body reaction when implanted for 3 weeks either intraperitoneally or beneath the kidney capsule of Lewis or non-diabetic BB/Gi rats.
Alginates↗
Effect of transplantation site and culture pretreatment on islet xenograft survival (rat to mouse) in experimental diabetes without immunosuppression of the host.
Recently, we reported on indefinite islet graft survival in allotransplantation (rat to rat). This was achievable without the use of any immunosuppression by performing transplantation of culture-pretreated (22 degrees C) islets of Langerhans under the renal capsule (r.c.) of chemically induced diabetic recipients. The aim of this study was to test this successful islet modulation technique in a xenogeneic animal model. Six groups of chemically induced diabetic, inbred, C57BL/6J mice received by transplantation either into the liver via the portal vein (i.po.) or under the renal capsule (r.c.) 300-350 either freshly or culture-pretreated (37 degrees C and 22 degrees C) Lewis rat islets without any immunosuppressive therapy. Histology was performed after rejection or post-transplant normoglycaemia (> 120 days) for evaluation of the graft. Transplantation of freshly isolated islets resulted in 75% graft rejection 17 days after transplantation. Using culture pretreatment at 37 degrees C, we noted 75% graft rejection 31 days after transplantation. In contrast, culture pretreatment at 22 degrees C resulted in a marked prolongation of xenograft survival, 75% graft rejection occurring 58 days after transplantation, and in two cases there was indefinite graft survival (> 120 days). Statistical analysis showed a significant prolongation of xenograft survival after culture pretreatment, with the most beneficial effect appearing after low-temperature culture at 22 degrees C (P < 0.05). Interestingly, xenograft survival was markedly prolonged only using the r.c. approach. Statistical comparison revealed a highly significant prolongation using the r.c. as transplantation site compared with i.po. (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Lymphoid activation by different crude alginates and the effect of purification.
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Alginates↗
Diabetes mellitus-associated decrease in nerve growth factor levels is reversed by allogeneic pancreatic islet transplantation.
After an untreated 5-month duration of streptozotocin (STZ)-induced diabetes mellitus (DM), nerve growth factor (NGF) levels in BDE rats were decreased to 45-65% of control in the sympathetically innervated target organs iris and submandibular gland, in the superior cervical ganglion (containing NGF-dependent sympathetic perikarya projecting to the cranial targets), and in the NGF-transporting sciatic nerve. Successful allogeneic pancreatic islet transplantation (providing a physiological glucose homeostasis without immunosuppression) after 3-4 weeks of DM reversed the DM-related decrease in NGF levels 4 months after transplantation as compared with untreated diabetic rats. By contrast, NGF levels in the treated vas deferens (innervated by short postganglionic sympathetic neurons) remained increased as in the untreated diabetic rats (175% of control). Thus, DM-associated changes in endogenous NGF levels seem to be reversible by institution of metabolic control, at least at an early stage of DM when NGF-responsive neurons have not been deprived of NGF for a long time.
Animals↗
[Islet transplantation in the treatment of diabetes mellitus: the challenges to the transplant of rejection and recurrent autoimmunity].
The success of islet transplantation for therapy of spontaneous diabetes mellitus depends on two immune responses of the recipient. The rejection of foreign tissue plays a major role in islet transplantation and can successfully be prevented by different immunomodulation in animals. In spontaneous diabetes the islet transplant can also be destroyed by the recurrent autoimmune insulitis. We describe, in which experiments recurrence occurred. We also demonstrate the influence of the donor-host combination on the immune attack and the possibilities to prevent the destruction of transplanted islets in animals. An outlook on the clinical situation is given.
Autoimmunity↗
Islet transplantation in experimental diabetes of the rat. XII. Effect on diabetic retinopathy. Morphological findings and morphometrical evaluation.
Digest-preparations of rat retinal vasculature were examined with respect to single capillary alterations and diffuse changes in cellular composition. Retinas of streptozotocin-diabetic rats revealed single micro-aneurysms, degenerated capillaries, strand formation, microthromboses and further lesions, occurring sooner than previously described. A severe loss of pericytes and a slight increase in endothelial cell number resulting in an increase in E/P-ratio were observed, all effects becoming more pronounced with longer duration of diabetes. Syngeneic islet transplantation could prevent all of the described alterations if carried out soon after diabetes induction. If performed six months later it was able to almost restore the normal cellular composition while pathomorphological lesions could be arrested or reversed only partially.
Animals↗
[Effect of autoimmune destruction and rejection on the function of transplanted islands of Langerhans in spontaneous diabetes in the BB rat].
In animals and human identical twin transplants the autoimmunity of naturally occurring diabetes may destroy transplanted islets, even if rejection is avoided. We studied the influence of transplant site (liver vs. kidney capsule) and pretransplant treatment (culture) on autoimmune damage and rejection of transplanted islets of Langerhans in BB-rats which spontaneously developed diabetes. Freshly isolated and in the liver transplanted islets were destroyed rapidly (on the base of autoimmune destruction, rejection or both). In contrary, the renal subcapsule shows to be immunologically privileged with long survival of transplants. Culture pretreatment of MHC-incompatible Lewis islets resulted in long survival of transplants, which was not true in case of MHC-compatible WF islets: immunological disparity of donor and recipient tissue might be most successful in preventing autoimmune damage and rejection.
Animals↗
Quantitative assessment of GABA-uptake sites in the neural lobe by electron-microscopic autoradiography.
Distribution of (3H)GABA in the rat neural lobe was investigated 5 min after intracarotid administration using quantitative electron-microscopic autoradiography. Specificity of (3H)GABA-uptake was tested by pretreatment of control animals with nipecotic acid. It was concluded that, apart from a small fraction in the perivascular spaces, radioactivity was present exclusively in pituicytes. The results confirm and quantify earlier in-vitro observations; they are compared with recent immunocytochemical findings that reveal the presence of glutamate-decarboxylase-containing axons in the neural lobe. It is concluded that there may be GABAergic terminals that lack an uptake mechanism for exogenous transmitter. Nevertheless, (3H)GABA autoradiography is useful in demonstrating other functional components of GABAergic systems, i.e., glial cells.
Animals↗
[The value of CT in the diagnosis of tumours of the cerebello-pontine angle. Comparison of various radiological, clinical and otological examination].
An attempt has been made to define the role of CT in the diagnosis of cerebello-pontine angle tumours; 190 patients with this suspected diagnosis were examined by CT (including intravenous contrast enhancement and CT air cisternography) as well as other radiological, otological, neurological and audiometric investigations. Amongst these methods, CT is of most value. A knowledge of the variations of the internal auditory meatus and measurements of the porus acousticus are essential for evaluating the computer tomographic appearances.
Adolescent↗