Search PubMed⌕ Search

Biomedical subjects

R Wyss

Publications and source records attributed to R Wyss.

At least 91 records · Page 5Linked to original sources

Altered protein kinase C in a mast cell variant defective in exocytosis.

The murine mast cell line PB-3c is dependent on interleukin 3 (IL-3) with respect to survival and proliferation. These cells also require IL-3 to display antigen-mediated serotonin release, which is coupled to a transient increase of cytosolic free calcium ([Ca2+]i). The antigen-mediated exocytosis is inhibited by phorbol 12-tetradecanoate 13-acetate (PTA), an activator of phospholipid/Ca2+-sensitive protein kinase. In contrast, the malignant mast cell variant PB-1 is IL-3 independent with respect to proliferation but is unable to undergo antigen-mediated exocytosis. Yet this cell line exhibits basal levels of [Ca2+]i, serotonin content, and numbers of IgE receptors comparable to those of PB-3c cells. Subcellular distribution studies revealed that the specific activity of cytosolic protein kinase C of PB-1 cells was only 40% of that found in PB-3c cells. Furthermore, the PB-1 cells showed a significantly higher specific activity of membrane-bound protein kinase C than PB-3c cells. Scatchard plot analysis of [3H]-phorbol 12,13-dibutyrate binding to intact PB-1 cells demonstrated the presence of 20% high-affinity (Kd = 6 nM) and 80% low-affinity (Kd = 60 nM) phorbol ester receptors, whereas PB-3c cells displayed only the low-affinity phorbol ester binding. Immunological characterization of protein kinase C from both cell lines revealed the presence of a normal 77-kDa protein kinase C holoenzyme in both cell lines. In addition, a 72-kDa protein kinase C-related protein band was found mainly in the membrane fraction of the PB-1 variant. It is suggested that this altered and membrane-bound form of protein kinase C may be involved in the blockage of the antigen-mediated exocytosis of PB-1 cells.

Animals↗

Progesterone dependence and extratrophoblastic origin of pregnancy-associated plasma protein-A (PAPP-A) in early pregnancy.

Pregnancy-associated plasma protein-A (PAPP-A) is a macromolecular glycoprotein produced in increasing concentration as pregnancy advances. PAPP-A is not specific to pregnancy since measurable levels have been found in non-pregnant females and in males. In non-pregnant females, PAPP-A is probably produced by the endometrium. The origin of PAPP-A in pregnant women is still controversial. In-vitro trophoblast and decidual explants both produce PAPP-A. So far, it is not known if the same applies to the in-vivo situation and to what extent these two tissues contribute to the circulating levels of PAPP-A. This study compares the circulating concentrations of PAPP-A and beta-hCG and progesterone in different pathological situations. In hydatidiform moles, beta-hCG levels are very high demonstrating an intense trophoblastic activity, whereas PAPP-A levels remain in the normal range. With spontaneous abortions, beta-hCG levels decline to very low values whereas PAPP-A continues to increase. These observations furnish indirect evidence for a major contribution to circulating PAPP-A levels by extratrophoblastic sites. Furthermore, PAPP-A levels decrease after administration of an anti-progesterone (RU486) either in-vivo or in-vitro. This is considered as a proof that PAPP-A levels in early pregnancy are progesterone dependent.

Abortifacient Agents, Steroidal↗

[Prevalence of 7 microorganisms in abnormal vaginal secretions (vaginitis)].

Seven microorganisms (N. gonorrhoeae, C. albicans, T. vaginalis, G. vaginalis, M. hominis, U. urealyticum and Streptococcus of group B) have been assayed in genital samplings of 164 asymptomatic women (control group) and of 374 women suffering from abnormal vaginal secretions (vaginitis group). All these bacteria except group B Streptococci were isolated in the vaginitis group more frequently than in the control group (p less than 0.01). The proportion of negative cultures for all tested bacteria was 39% in the control group and 6.4% in the vaginitis group (p less than 0.01). This shows an association of these bacteria with 70% of the patients of the vaginitis group and with only 26% of the women of the control group (p less than 0.01). It is to be noted that the pH values are higher in the group of women with vaginitis than in the control group (p less than 0.01). Comparison of the microbial flora during "specific" an "non-specific" vaginitis indicates that G. vaginalis is isolated more frequently in patients with non-specific vaginitis than among those with specific vaginitis (p less than 0.01). Likewise, M. hominis is isolated more frequently in groups of women with either non-specific vaginitis or T. vaginalis vaginitis, than in groups of patients with a C. albicans vaginitis (p less than 0,01). The results of this study indicate that there is a causal relationship between vaginitis and the presence of T. vaginalis. C. albicans, G. vaginalis, M. hominis or N. gonorrhoeae, either as a single or a mixed infection, and that there is a relationship between increased pH values and abnormal vaginal secretions.

Adult↗

Early ultrastructural changes in RU-486-exposed decidua.

An antiprogesterone (RU-486) was administered to women undergoing voluntary interruption of pregnancy. Five patients received 100 mg 12 h before surgical interruption, 5 others received 100 mg twice, 24 and 12 h before interruption, respectively, and another 5 received no drug at all and served as controls. Placentas and deciduae were examined morphologically with the light microscope and by electron microscopy. No specific lesions were detected in placental tissue. With conventional histology, the deciduae showed various degrees of interstitial edema and necrosis, changes which did not enable a distinction between treated cases and controls, although stromal disintegration tended to be more marked in RU-486-treated patients. At the ultrastructural level, the endothelium of decidual capillaries showed striking hyperplasia of the endoplasmic reticulum. Morphometric evaluation showed a statistically significant difference between RU-486-treated patients (2 X 100 mg) and controls. A possible link between these morphological changes and the induction of prostaglandin synthesis by the antiprogesterone is suggested. However, the full significance of the observed lesions remains uncertain and does not allow definite conclusions concerning the abortifacient effect of RU-486.

Capillaries↗

[The effects of an antiprogesterone steroid in women: interruption of the menstrual cycle and of early pregnancy].

RU-486 is a steroid which possesses a great affinity for the progesterone receptor, does not have a progesterone activity, but is indeed a strong antagonist of progesterone effects in animals. Oral administration induces the interruption of the luteal phase of the menstrual cycle and that of early pregnancy in women. Its mode of administration and its properties enable us to envisage a new methodology for menstrual cycle regulation and human birth control.

Abortifacient Agents↗

[Maturation of the cervix by prostaglandins before inducing termination of pregnancy, in the first trimester (author's transl)].

A new technique for instilling the gel of PGF2 alpha into the endocervix is presented. The study is concerned with 100 therapeutic terminations of pregnancy by dilatation and suction carried out in the first trimester of pregnancy. The efficacy of PGF2 alpha gel is compared with that for tablets of PGE2 and a placebo group. Softening of the cervix was evaluated using a tocodynamometer. PFG2 alpha gel often gives remarkable results, but the response to treatment is unpredictable. Secondary effects, and in particular digestive effects, occur frequently but are always easily controlled.

Abortion, Induced↗