Distinct expression of endothelin receptor subtypes A and B in luteinized human granulosa cells.

Endothelins (ET) are potent vasoconstrictive peptides originally isolated from vascular endothelial cells. Their biological effects are mediated through two different receptors, the endothelin-1 (ET-1)-selective endothelin receptor subtype ETA and the non-selective receptor subtype ETB. ET-1 protein has been found in human ovarian follicular fluid and ET-1 mRNA expression has been demonstrated in ovarian tissue. These findings indicate that the endothelin-system participates in the modulation of ovarian function, probably acting in an autocrine/paracrine manner. In the current study we used freshly aspirated, luteinized human granulosa cells (hGC) representing an in vitro model of the early corpus luteum. By means of RT-PCR and immunocytochemistry we investigated whether luteinized human granulosa cells express ETA and ETB receptors. Specific amplification products of ETA transcripts were detected in all samples investigated. In contrast, only after using a three-fold amount of ETB reverse transcripts we were able to demonstrate specific, but weak amplification products. In addition, immunocytochemical staining for ETA but not for ETB was found in granulosa cell preparations. The present study provides clear evidence that human granulosa cells predominantly express ETA receptor subtype mRNA and protein hinting to its possible role in follicle maturation and corpus luteum formation.

Ovarian carcinoma: increase in clinical validity by simultaneous determination of SRA and CA 125.

Ovarian carcinomas are distinguished by their polyclonality, i.e., heterogeneity and polymorphism of their tissue. There is no marker available complying with the clinical demands in the case of ovarian carcinoma regarding satisfactory sensitivity and specificity. Therefore, we have simultaneously determined two entirely distinct tumor markers, serum ribonuclease activity (SRA) and cancer antigen 125 (CA 125), recommended in the literature with respect to ovarian carcinoma. After evaluation by logistic regression analysis, we found a specificity of 93% together with a sensitivity of 97% for the simultaneous determination of SRA and CA 125 (37 ovarian carcinomas, 11 cases without pathological findings after treatment, 11 benign tumors of the ovary, 61 controls). The patients are not exposed to increased stress by this simultaneous determination method compared to the determination of a single marker. The increased clinical validity justifies the recommendation of routine simultaneous determinations of SRA and CA 125 for diagnosis and monitoring of patients with ovarian carcinoma.

Serum ribonuclease activity in patients with ovarian tumors.

The RNase activities have been assayed in 1678 serum samples from a total of 209 patients. 52 with histologically confirmed ovarian carcinoma, 13 with benign tumors of the ovary, and 144 patients without any clinically detectable malignancy. The serum RNase activity is unequivocally increased in the group with ovarian cancer (p less than 0.01). Considering the distribution of the RNase activities with a margin at 300 ngeqvs/ml serum we find 8.3% false negative and 4.9% false positive results. The serum RNase activity does not display any evident relationship with tumor spread, histology, clinical grading (TNM), nor metastasis at the time of the blood taking. It is concluded that the serum RNase activity is a meaningful criterion together with the careful clinical examination for the diagnosis and the surveillance of ovarian cancer.

Determination of ribonuclease activity in the serum of ovarian carcinoma patients.

Increased serum ribonuclease activity represents a phenomenon of ovarian carcinoma. We have developed a convenient sensitive and reproducible assay system to determine the ribonuclease activity in human serum. The influence of various factors and conditions like storage, pH, salt, heparin, and the accuracy of the determination of HSRA was investigated.

[Serum ribonuclease activity in gynecologic neoplasms. The behavior of serum ribonuclease in ovarian cancer under cytostatic therapy]. / Serumribonuklease-Aktivität als Parameter bei gynäkologischen Malignomen. Das Verhalten des Serumribonuklease-Spiegels bei Ovarialkarzinomen unter zytostatischer Therapie.

Ribonuclease activity in the serum of patients with histologically confirmed ovarian carcinoma is significantly higher than in serum of patients with benign tumors of the ovary and that of healthy controls. In 847 samples collected during a period of 20 months the course of the ribonuclease activity of 41 patients receiving cytostatic treatment was determined. The ovarian carcinoma of all 41 patients was histologically ascertained. Three typical examples are presented.

Increasing human serum ribonuclease activity is a concomitant phenomenon of ovarian carcinoma.

The levels of total human serum RNAase activity (HSRA) from 24 patients with ovarian cancer have been followed up for a period of over 5 months. The determinations of HSRA were carried out according to our assay system described earlier. Two representative patterns of the HSRA are presented, one from a patient with an ascertained remission of an ovarian carcinoma. Increasing HSRA values are concomitant with tumor progression while in remission the HSRA remains at normal rates. We have reported earlier that optimum HSRA depends on physiological concentrations of NaCl in the reaction mixture. However, NaCl can be replaced by KCl without a loss of activity. No correlation was detectable between increased HSRA and an excessive electrolyte content in serum. The mixtures of sera with various RNAase activities showed linear additivity. These findings suggest that an increased concentration of the RNAases normally present in human serum and/or additional RNAases are responsible for the increase of the HSRA.

[Serum ribonuclease activity in patients with gynaecologic malignomas (author's transl)]. / Ribonukleaseaktivität bei gynäkologischen Malignomen.

The aim of our work was to evaluate the diagnostic value of the determination of the ribonuclease activity in sera of patients with gynaecologic malignomas. We therefore developed an assay for ribonuclease activity. In the course of optimization of the assay conditions we investigated the applicability of 4 commercially available RNA-preparations as substrate and the dependency of the ribonuclease activity on salt-concentration. The ribonuclease activity of 42 representative female patients (12 controls, 11 with ovarian carcinoma, 10 with corpus carcinoma, 9 with collum carcinoma) is presented.

Replacement of wybutine by hydrazines and its effect on the active conformation of yeast tRNAPhe.

The highly modified base wybutine (YWye) next to the anticodon of yeast tRNAPhe has been replaced by different hydrazine derivatives. The effect of the replacement on the activity of the tRNA has been studied in the heterologous aminoacylation with synthetase from E. coli and in the poly(U) directed binding to ribosomes from both yeast and E. coli. It was found that starting from tRNA-PheYWye the activity increased with increasing size, aromaticity, and stacking tendency of the substituent replacing YWye. It is concluded that YWye by the size of its aromatic system and by its stacking properties is particularly well suited for stabilizing the native conformation of tRNAPhe.