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Biomedical subjects

K Buhler

Publications and source records attributed to K Buhler.

5 recordsLinked to original sources

[In Process Citation]

GnRH agonist (GnRHa) administered for 6 months leads to an effective desensitisation of the pituitary and hypoestrogenism without exerting a particular effect on the whole metabolism. At the end of the first month's a suppression of the serum estradiol levels are achieved, the level of LH and FSH decline in the hypogonadotropic range. No negative influence on the lipid metabolism after administration of GnRH agonist has been observed. The balance of HDL/LDL does not change during the treatment. There were neither any negative changes in the liver metabolism, kidney function nor in the electrolyte values. In anaemic premenopausal women, for example due to serious menstrual problems, a normalisation of the haemoglobin concentration is obtainable already after a 12-week treatment. With regard to the hemostatis system a significant reduction of the procoagulant activity, fibrin turnover rate and a significant improvement of fibrinolytic activity can be observed under a GnRHa therapy. Although the use of GnRHa leads without doubt to a drastic reduction in the uterus blood flow there are no signs that this also leads to a change in the cerebral arteries blood flow. Menstrual bleeding occurs on average 3 months after the last injection of an GnRHa depot injection; with daily injection or nasal spray 3 to 4 weeks earlier. Theoretical considerations as well as the world-wide use as part of the infertility treatment--in some countries more than 90% of all IVF-cycles are performed using GnRH--,contradict the fact that GnRHa cause a teratogenic effect. Domineering undesirable side-effects during a treatment with GnRH can be traced back almost exclusively to the effective hormonal deprivation. In this context it is remarkable which percentage patients complain about trouble of this spectrum before GnRHa treatment is initiated. The chronicle reduction of the sexual hormone level leads without a doubt to a reduction of bone mineral density. The clinical relevance is furthermore a matter of controversial discussion. Prevention measures can be undertaken through an add-back therapy. This can also be of help in the case of vegetative side-effects caused by a decrease in sexual hormones. The question arises to what extent effective non hormonal add-back therapies are at disposal in the treatment of sexual hormone related malignant tumours. Also men with testosterone deprivation can suffer from distinctive hot flushes, sleeping disturbances and depression which requires some kind of relief in order to maintain an acceptable quality of life.

Journal Article↗

Immunosuppression of T lymphocyte function by fractionated serum from tumor-bearing mice.

Sera from mice with transplanted 3-methylcholantrene-induced tumors have been shown previously to inhibit the function of normal lymphoid cells. When chromatographed on Sephadex G-150, the fraction eluting with immunoglobulin has been shown to inhibit the proliferative response of normal spleen cells to concanavalin A and to inhibit the in vitro antibody response to a T-dependent antigen, but has a lesser effect on the antibody response to a T-independent antigen. This paper deals with studies on the mode of action of the serum factor. The immunoglobulin containing fraction of serum from tumor-bearing mice inhibited the in vitro generation of both allogeneic and syngeneic cytotoxic lymphocytes. Time course studies demonstrate that the serum fraction inhibits the generation of antibody-producing and cytotoxic lymphocytes if added during the first 2 days of a 5-day culture. Serum fractions added after day 2 had no effect on the in vitro response. The serum factor appears to inhibit the generation of specific T cell function during the proliferative stage of development but has no effect on the differentiation stage which leads to either antibody-producing cells or cytotoxic lymphocytes.

Animals↗

Immunosuppression of T lymphocyte function by fractionated serum from tumor-bearing mice.

Sera from mice with transplanted 3-methylcholantrene-induced tumors have been shown previously to inhibit the function of normal lymphoid cells. When chromatographed on Sephadex G-150, the fraction eluting with immunoglobulin has been shown to inhibit the proliferative response of normal spleen cells to concanavalin A and to inhibit the in vitro antibody response to a T-dependent antigen, but has a lesser effect on the antibody response to a T-independent antigen. This paper deals with studies on the mode of action of the serum factor. The immunoglobulin containing fraction of serum from tumor-bearing mice inhibited the in vitro generation of both allogeneic and syngeneic cytotoxic lymphocytes. Time course studies demonstrate that the serum fraction inhibits the generation of antibody-producing and cytotoxic lymphocytes if added during the first 2 days of a 5-day culture. Serum fractions added after day 2 had no effect on the in vitro response. The serum factor appears to inhibit the generation of specific T cell function during the proliferative stage of development but has no effect on the differentiation stage which leads to either antibody-producing cells or cytotoxic lymphocytes.

Chemical Precipitation↗

Microvascular endothelium of human tumor xenografts expresses mouse (= host) CD31.

BACKGROUND: Human malignant tumors grown as xenografts in immunocompromised animals have been used extensively to study tumor growth and tumor response to therapy. The endothelium functions as an effective barrier between the intravascular space and the tumor cells. In a previous study we used species-specific monoclonal antibodies against endothelial cell adhesion molecules to demonstrate the host origin of the endothelium in xenotransplanted pancreatic islet grafts [Am J Pathol 1995;146:1397-1405]. We now investigated in this study whether the vascular endothelium of different xenografted human malignant tumors expresses mouse (= host)- or human (= graft)-specific CD31 (platelet endothelial cell adhesion molecule, PECAM-1) adhesion molecules. METHODS AND RESULTS: Cultured human prostate, kidney, and colon cancer cells (passages 15-17) were transplanted subcutaneously into 8-week-old athymic nude mice and removed after another 8 weeks. The avidin biotin peroxidase method was utilized on frozen sections to demonstrate that the endothelium of the vasculature of all three human xenografts expressed mouse (= host)-specific CD31, but not human (= graft)-specific CD31. CONCLUSION: The presence between the intravascular space and the human tumor cells of a mouse-derived endothelium, expressing mouse-specific antigens, needs to be taken into careful consideration when evaluating results of antitumor therapies in these animal models. This caveat pertains particularly to the study of novel cell- or tissue-specific treatment modalities, such as antibody-targeted drugs, toxins or radionuclides, 'immuno'-liposomes, or tumor vaccines.

Animals↗