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Biomedical subjects

G L Floersheim

Publications and source records attributed to G L Floersheim.

At least 55 records · Page 3Linked to original sources

[Recipient conditioning with beagle plasma and beagle liver: prolongation of kidney-graft function without preoperative lymphocytotoxic antibody formation].

Donorspecific recipient conditioning in the non-related beagle produces prolonged kidney-graft survival without any postoperative immunosuppression. Besides 2 donor blood injections on days--18 and--11 followed by a 6-day preoperative immunosuppressive pulse (Procarbazine, ATS) donor plasma and a donor liver preparation are equally active. Additional long-term low dose preoperative immunosuppression with azathioprine tends to strengthen the effect. Lymphocytotoxic antibody formation is avoided in the recipient where no whole blood is used.

Animals↗

[Immunosuppression as a concomitant effect].

1. It is becoming increasingly clear that besides traditional immunosuppressive agents, an array of miscellaneous influences and conditions, as well as drugs used for other purposes, can affect the immune system. The potential pathogenetic role of immunity in an ever growing number of diseases, including infections, cancer, and autoimmune processes, confers on the concept of concomitant immunosuppression or immunotoxicology its due place in the discipline of immunopharmacology. 2. Microorganisms such as viruses, bacteria, and protozoa (and their products), as well as parasites, may depress immune reactivity. The mechanism of action, dose-response dependency, effect of timing, and relation to bacterial adjuvanticity need more thorough exploration. 3. The efficacy of immunosuppressive drug protocols can be improved by combining immunosuppressants without bone marrow toxicity, such as niridazole or free fatty acids, with the standard antiproliferative immunosuppressive agents. 4. Prostaglandin is a likely candidate for an essential role as an immunosuppressive effector. Its release from T-suppressor cells is triggered for example by microorganisms. Moreover, dietetic and metabolic factors, such as free fatty acids, and nervous impulses affect prostaglandin formation. If thus constitutes a link between the nervous system and, on the other hand, immunity and possibly cancer.

Adjuvants, Immunologic↗

[Preoperative immunosuppression in the kidney-transplanted dog in connection with specific antigenic pre-treatment].

Postoperative, nonspecific routine immunosuppressive therapy fails in up to 50% in human cadaver renal transplantation. Donorspecific preoperative immunological conditioning of the host is harder to induce in dogs than in some rodents. In a pilot study 2 i.v. donorblood injections on days -18 and -11 followed by a 6-day preoperative pulse without any postoperative therapy induce a significant albeit limited prolongation of graft function.

Animals↗

[Blood transfusion and kidney transplantation].

The non-transfusion policy for potential recipients of kidney allografts that has been followed in recent years has not proven successful. There is now ample clinical evidence of improved transplant function in the transfused recipients category. This has also been confirmed in recipients of a first cadaver kidney in Basel and Geneva. If the conditions valid for human kidney transplantation are matched as closely as possible in animal experiments, prolongation of graft function rather than accelerated rejection is usually observed after blood transfusions. Potential kidney graft recipients should be more liberally transfused and experimental evidence ought to be accumulated in order to establish a rationale for optimal host conditioning, while avoiding the hazards of blood transfusions to the greatest extent possible.

Animals↗

Ethanol and tolerated doses of Amanita phalloides protect against lethal doses of the mushroom.

Single tolerated doses of a lyophilizate from Amanita phalloides (ADL) failed to increase the survival rate of mice after the LD90 of the mushroom. Also, pretreatment with large doses of ethanol did not protect against lethal doses of APL. However, with combined administration of single tolerated doses of APL and of ethanol, the survival rate of mice after a lethal challenge with APL was increased from 13% to up to 100%. Both ethanol and APL potentiated the effect of barbiturate narcosis, but the combined pretreatment was not more effective. The protection against APL afforded by the combined regimen may be due to inhibition of activating hepatic microsomal enzymes, but biochemical studies are needed to support this hypothesis.

Amanita↗

Bone marrow transplantation after lethal chemotherapy in "nude" mice.

Isogenic bone marrow transplantation was performed in "nude" and normal C3H mice after lethal doses of dimethylmyleran (DMM), meso-DMM, and (+/-) DMM were given. Nude mice were not more sensitive to DMM or its isomers than normal mice. With adequate cell doses in the range of 3 X 10(6) to 30 X 10(6) bone marrow cells or 10 X 10(6) to 30 X 10(6) spleen cels, the survival rate after lethal chemotherapy was not significantly different between nude mice reconstituted with a graft from nude donors and normal mice reconstituted with a graft from normal donors. Only with suboptimal cell dose (1 X 10(6) bone marrow cells) was survival superior in normal mice. Thinsic factor. Nude mice accepted also bone marrow grafts from allogeneic nude donors.

Animals↗

Cytochrome C as antidote in mice poisoned with the mushroom toxin alpha-amanitin.

The curative potencies of cytochrome c applied 8 hours after lethal doses of alpha-amanitin in mice are confirmed. In a comprehensive series of experiments, various dosage schedules were explored. Optimal effects with cure rates approaching 100% were obtained either with repeated doses of cytochrome c or by combining it with penicillin. Male mice are more sensitive to alpha-amanitin than female mice but it was established that the antidote is effective in both sexes. Substantial cure rates are seen even when the treatment after supralethal doses of alpha-amanitin is withheld for 12 hours after the poisoning.

Amanita↗

[Human non-epithelial tumors in "nude" mice: morphology and growth characteristics].

Morphology and growth characteristics of an osteosarcoma and a glioblastoma are described after direct transplantation in nude (thymusless) mice. In osteosarcoma neither characteristic had changed after 14 months' observation. In contrast, some of the glioblastoma transplants (22 months' observation) showed dedifferentiation of morphology and grew faster than others derived from the same biopsy. The possible reasons for the different growth pattern of the two tumors are discussed.

Animals↗

Antagonistic effects against single lethal doses of Amanita phalloides.

Agents with antagonistic effects against phalloidin or alpha-amanitin were tested in mice against lethal doses of an extract from the whole mushroom Amanita phalloides. The following categories of agents reduced lethality after the extract. First, agents protecting only against phalloidin such as rifampicin, phenylbutazone and antamanide. Second, silymarin and prednisolone which display both antiamatoxic and marked (silymarin) or moderate (prednisolone) anti-phallotoxic acitivty. Thioctic acid displayed some activity when tested against mid-lethal doses of the extract. Cytochrome c, a chemical with curative potencies against alpha-amanitin did not reduce the lethality of the exact. All of the effective agents acted only when applied prior to the poisoning. The pattern or protective activity would indicate that in mice death after single doses of Amanita phalloides may follow a qualitatively particular couse which is difficult to ascribe to phallo- or amatoxic effects alone.

Agaricales↗

Reconstitution capacity of bone marrow cells from nude mice in radiation chimeras.

Lethally irradiated mice were reconstituted with bone marrow cells from 'nude' or normal mice. It was found that the radioprotective capacity of bone marrow cells from normal and thymusless 'nude' mice is similar and that the immune responses to sheep red cells in radiation chimeras reconstituted with normal and nude bone marrow cells are also similar. Bone marrow cells from nude mice, in spite of the lack of the thymus, develop into hematopoietic cells and contain also T-precursor cells.

Animals↗

[Viewpoints on the pharmacological suppression of immunologic reactivity].

The pharmacological alteration of immunological reactivity is considered. The immunosuppressive drugs may be classified according to their chemical class and their antigen- or cycle-dependency. A relative specificity towards the lymphoid system is cyclophosphamide. New vistas are opened by the modulation of immunological reactivity by cyclic nucleotides. The possibilities afforded by the combined use of immunosuppressive drugs have not been fully exploited. A short therapeutic program including donor antigen, procarbazine and antilymphocyte serum induces immunological tolerance to allogeneic skin grafts in mice and bone marrow allografts in dogs. Immunosuppressive properties of microorganisms are exemplified.

Adjuvants, Immunologic↗