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Biomedical subjects

K Pollow

Publications and source records attributed to K Pollow.

At least 37 records · Page 2Linked to original sources
PubMed1999

[Renal morphometric investigations in pre-eclampsia-like syndrome in a Wistar rat model].

OBJECTIVE: Etiology and pathogenesis of renal changes in pregnancy-induced hypertension (PIH) remain somewhat controversial. Reducing the uterine perfusion leads to the development of systemic hypertension in animal models. Aim of this study was to investigate the effect of systemic hypertension on the kidney during pregnancy. MATERIAL AND METHODS: A rat model was used and the degree of the renal changes was quantified by morphometry. Normotensive pregnant and virgin animals served as a control. RESULTS: Hypertensive animals showed a decrease of the intravascular space in comparison to the cellular component. This difference was significant not only in pregnant (p = 0.0026) but also in virgin (p = 0.001) animals. CONCLUSIONS: These findings indicate that renal changes are usually found in normotensive pregnancies, while PIH strongly aggravates these changes.

Animals↗
PubMed1999

[Value of p53, urokinase plasminogen activator, PAI-1 and Ki-67 in vulvar carcinoma].

OBJECTIVE: The present study was to measure new prognostic factors including the plasminogen activator urokinase and the plasminogen inhibitor PAI-1, as well as p53 and Ki-67, a marker of proliferation and to compare the clinical value of these in relation to the classic histopathological prognostic factors. MATERIAL AND METHODS: The patient collective included 45 patients with vulvar carcinoma, both primary tumors and recurrences. RESULTS: Highly significant correlations were found for tumor diameter and thickness. According to Kaplan-Meier estimations, the influence of thickness on the prognosis had a p-value of 0.048, while the influence of diameter had a p-value of 0.029. The variable grading was also significantly associated to the probability of survival (p = 0.01). There was no statistically significant correlation between p53 and the parameters grading, degree of keratinization and Ki-67 color index. The correlation between p53 and PAI-1 as well as between UPA and PAI-1 was highly significant. According to the Kaplan-Meier estimations, Ki-67, UPA and PAI-1 had no influence on survival in our group of patients. CONCLUSIONS: For p53, the median value could be used as a divider with the median survival of patients with a p53 below 122 pg/mg protein being 151 months and with a p53 above 122 pg/mg being only 61 months. The corresponding p-value was significant at 0.0201.

Adult↗
PubMed1998

[Gynecologic endocrinologic information sources in the internet].

Within the last months a great number of internet pages have become a highly interesting source of up-to-date information in gynecological endocrinology. Most of these World Wide Web-pages present actual scientific fields and abstracts with close relations to basic science, while clinical discussion groups are still rare. The potential of internet presentations will strongly influence communication in cases of gynecological endocrinology.

Computer Communication Networks↗
PubMed1996

[Circadian blood serotonin and melatonin level in anorexia nervosa patients in comparison with normally menstruating women].

Day and night rhythms of melatonin and serotonin were measured in four female anorexia nervosa patients and for comparison in a control group with normal 28-day menstrual cycle. In the anorexia nervosa group the levels of gonadotropins and sexual steroids were distinctly lowered. In the LHRH test the hormonal profile showed pubertal to prepubertal patterns of secretion with an only moderate increase of LH and distinct shifting of the LH/FSH ratio in direction of FSH. For both groups the 24-hour profiles of melatonin and serotonin showed a normal cycle, i.e. melatonin had its maximum by night, whereas serotonin in contrast displayed its highest values by day. However, in the group of patients with anorexia nervosa the maximum of melatonin was on the average 2.1 fold higher than that found in the control group, whereas that of serotonin was 1.4 fold higher. A close functional coherence between the neurotransmitters melatonin and serotonin and the hypothalamic secretion of LHRH is being discussed.

Adolescent↗
PubMed1996

Unruptured tubal pregnancy: local low-dose therapy with methotrexate under transvaginal ultrasonographic guidance.

Thirty patients with unruptured ectopic pregnancy (4-10 weeks' gestation) were treated locally with methotrexate (MTX) under sonographic guidance. The transvaginal puncture was performed under analgesic sedation using an automatic puncturing device. Local MTX therapy was successful in 25 patients (83.3%). Eighteen of these patients had received a single MTX instillation with a total dose of 10 mg, 7 patients had received a second instillation with 10 mg because of plateauing hCG levels after the first instillation. In 5 patients MTX therapy was unsuccessful. Surgical intervention was necessary within 4 h to 15 days after MTX treatment, due to severe tubal bleeding (n = 1) or the development of an increasing peritubal hematoma (n = 4). Patients with an outer trophoblast diameter < or = 1.5 cm could be treated successfully in all cases (25/25). In patients with hCG values > 5,000 mIU/ml the success rate was 70% (7/10) and in patients with demonstration of cardiac activity of the embryo 63% (5/8). The fluid aspirated from the ectopic cavity showed an average hCG concentration that was 53 times higher than in the serum. The decline in hCG to values below 10 mIU/ml ranged between 7 and 75 days (mean 28 days). The hysterosalpingography performed 4-6 months after MTX therapy showed tubal patency on both sides in 85.7% of the patients examined. In the meantime 4 of these patients gave birth to healthy children.

Adult↗
PubMed1995

[Synthesis and reactions of 2-methylene-canrenone].

Starting from the Mannich salt 1 of the aldosterone antagonist canrenone or from 2-methylene-canrenone (2) the A-ring annulated hetero- and carbocycles 5, 6, 8-13 were prepared. Receptor (estradiol, progesterone, androgen, gluco- and mineralocorticoid) binding studies and competition studies with the serum proteins SHBG and CBG were carried out using the compounds 2, 3, 4b, 5, 6b, 8 and 12. The relative binding affinities with CBG are below 1%, in all other cases lower than 0.01%.

Animals↗
PubMed1995

[Heterocyclic annulated steroids from 2-hydroxymethylene-canrenone].

A-ring annulated heterocycles, the isoxazole 6, the pyrazoles 8 and the pyrimidines 9 are prepared starting from 2-hydroxymethylene canrenone 1. Binding studies were carried out with the compounds 1 and 6-8 using estrogen, progesterone, androgen, gluco- and mineralocorticoid receptors as well as the serum proteins SHBG and CBG: the substances were inactive on the receptor level. 1, 7 and 8a show weak binding affinity to CBG.

Animals↗
PubMed1995

[Acetylation of spironolactone, canrenone and 2-methyl-canrenone].

Reaction of the title compounds with acetic anhydride and acetyl chloride yields the 3,5-dien-3-yl acetate 2, the isomeric 2,4,6- and 3,5,7-trien-3-yl acetates 3 and 4 as well as the 2,4,6,8(14)-tetraen-3-yl acetate 7. The 2 alpha-methyl-8,14-didehydro-canrenone (9) is obtained by hydrolysis of 7. Binding affinities of 7 and 9 to hormone receptors as well as serum proteins (SHBG, CBG) are investigated. The compounds are inactive.

Acetylation↗
PubMed1995

[Hormone receptor determination in breast carcinoma tissue. Comparison of recent immunohistologic techniques with biochemical receptor testing].

For evaluation of the hormone receptor status in breast cancer tissues two methods are mainly used: immunohistochemical detection by monoclonal antibodies on frozen sections (ER-ICA, PgR-ICA) and the biochemical radioligand-binding assay (DCC) of fresh tissue. Using new antibodies makes it possible to evaluate the estrogen and progesterone receptor status in formalin-fixed and paraffin-embedded tissue. In the present retrospective study, tissues from 223 primary breast carcinomas or breast carcinoma recurrences were re-evaluated with the three methods mentioned above and the results were compared. We used antibody 1D5.26 reacting with the estrogen receptor and mPR1 specific for the progesterone receptor in paraffin-embedded tissue. The agreement of positive and negative cases between these two immunohistochemical procedures was 97.8% for the estrogen receptor and 85.7% for the progesterone receptor. Comparison of immunohistochemistry on paraffin-embedded tissue and biochemical evaluation showed an agreement of 74.7% for the estrogen receptor and 68.7% for the progesterone receptor. These results are comparable to the correspondence between ER-ICA and PgR-ICA and the DCC method. This study proves that the prognostically and therapeutically important hormone receptors can be reliably determined in formalin-fixed and paraffin-embedded tissues. These results are not only important for the evaluation of hormone receptors of a small breast carcinoma that is not found in the frozen section, but for the considerable difference in costs among the different methods.

Antibodies, Monoclonal↗
PubMed1994

Immunohistochemical detection of hormone receptors in breast carcinomas (ER-ICA, PgR-ICA): prognostic usefulness and comparison with the biochemical radioactive-ligand-binding assay (DCC).

In a prospective study conducted since 1983, the hormone-receptor status of primary breast carcinomas was investigated using immunohistochemical (ER-ICA, PgR-ICA) and biochemical (DCC) methods. The degree of immunohistochemical staining was evaluated according to the immunoreactive score (IRS) devised by Remmele and Stegner [Frauenarzt 28, 41-43 (1987)]. The findings obtained using the biochemical radioactive-ligand-binding assay (cutoff level, 20 fmol/mg) and those obtained using qualitative immunohistochemical methods were in agreement in 72.5% (ER-ICA) and 72.2% (PgR-ICA) of cases. For the 789 cases of primary breast carcinoma examined, postoperative data were available for a mean follow-up period of 48 months. Using the statistical procedure of Kaplan-Meyer to analyze the probability of disease-free and overall survival, it emerged that ER-ICA- and PgR-ICA-positive breast carcinomas exhibited the most favorable course of disease. Breast carcinomas with negative immunohistochemical findings for both types of receptor were found to have a significantly less favorable disease course. Semiquantitative evaluations of the staining results using the IRS failed to yield significant differences among the 12 IRS groups. Neither the percentage of positive tumor cells nor the immunohistochemical staining intensity proved to be prognostically useful parameters for predicting the course of disease. In comparison to the established biochemical method for the demonstration of hormone receptors, however, the immunohistochemical procedure was found to be superior with respect to prognostic meaningfulness, particularly in the group with conflicting biochemical and immunohistochemical findings with respect to hormone-receptor status. Using Cox analysis, the prognostic usefulness of the immunohistochemical test was compared with that of certain established prognosis parameters (pT, pN, grading, Ki-67), from which it became apparent that PgR-ICA has the greatest prognostic value, with the most lasting influence on the course of disease. The results of the present study demonstrate that, with respect to the prognostic value of its findings, the immunohistochemical test for hormone receptors is superior to the biochemical procedure.

Breast Neoplasms↗
PubMed1993

Establishment and characterization of six new human endometrial adenocarcinoma cell lines.

The endometrial carcinoma cell lines EC-MZ-1, 2, 3, 5, 9, and 11 were established between 1986 and 1990. Four cell cultures were started from endometrial tissue, one from ascites, and one from a lymph node metastasis. Lines have to date been subcultured up to 180 times and the doubling time varies between 26 hr and 3 weeks. Immunocytochemically the coexpression of cytokeratin (predominantly simple-epithelial cytokeratin polypeptides) and vimentin intermediate filaments was detectable in all cell lines, but three lines (EC-MZ-5, 9, 11) expressed vimentin only at low level. By transmission electron microscopy the tumor cells exhibited features of epithelial differentiation. After subcutaneous transplantation into nude mice three lines (EC-MZ-1, 2, 5) produced slow-growing tumors. The histological classification of these tumors ranged from moderately differentiated adenocarcinoma to undifferentiated carcinoma and closely corresponded to the original tumor. Even after long-term in vitro culture, without any addition of estrogens to the culture medium, the moderately differentiated receptor-positive cell line (EC-MZ-2) retained its morphological differentiation. The cells were propagated without estrogens in the culture medium. The estrogen and progesterone receptor levels of cultured cells were determined. Three lines (EC-MZ-1, 2, 3) were positive for the progesterone receptor in low passage number only, the other cell lines were negative for both receptors. The transplantable lines were investigated for hormonal receptor expression in ovariectomized nude mice. In the moderately differentiated cell line (EC-MZ-2) we observed an enhanced expression of the estrogen receptor under optimal stimulation of the nude mouse with estradiol benzoate. There was no effect on the expression of the progesterone receptor.

Adenocarcinoma↗
PubMed1993

Receptor binding of norgestimate--a new orally active synthetic progestational compound.

Binding of the new progestagen, norgestimate (D-(-)-13 beta-ethyl-17 beta-acetoxy-17-ethinyl-4-gonen-3-one-oxime), and its metabolites (levonorgestrel-3-oxime, levonorgestrel-17-acetate and levonorgestrel) to the progesterone receptor was investigated by competition experiments using cytosol from human myometrial tissue. Compared to R5020, a highly potent synthetic ligand for progesterone receptor analysis, the L-isomer of norgestimate shows only a weak specific behaviour with regard to binding to the progesterone receptor from uterine cytosol with an RBA value of 0.8%, whereas the D-isomer of this compound is characterized by a lack of binding activity to the progesterone receptor. Levonorgestrel-3-oxime, one of the possible metabolites of norgestimate, binds to the progesterone receptor with an RBA value of 8%, whereas levonorgestrel-17-acetate, the other possible metabolite of norgestimate, binds with a binding affinity of 110% which is in the same order of magnitude as levonorgestrel itself. The competition experiments suggest that norgestimate is a prodrug and that the metabolites, levonorgestrel and levonorgestrel-17-acetate, which actively bind to the progesterone receptor, must first be formed from the parent drug via metabolic processes in vivo. These are the actual biologically active compounds which are responsible for the gestagenic potency.

Animals↗
PubMed1992

Morphological, immunohistochemical and biochemical characterization of 6 newly established human ovarian carcinoma cell lines.

Six permanent human tumor cell lines (OV-MZ-1 to 6) were established from 6 patients with serous adenocarcinomas of the ovary. These cell lines were derived from both solid tumors and ascites, from pre-treated and untreated patients, and are available over a range of in vitro passage numbers. The tumor cells grow as monolayers and develop foci of "piled-up' cells in confluent cultures. Flow cytophotometry showed that all the lines exhibited DNA hyperdiploidy with DNA tetraploidy in one cell line and DNA aneuploidy in the other cell lines. The mean population doubling time ranged from 24 to 52 hr. Transmission electron microscopy demonstrated that the tumor cells of all cell lines exhibited features of epithelial differentiation such as desmosomes and intracellular gland-like lumina. Immunocytochemical analysis showed that the co-expression of cytokeratins and vimentin, which is a feature of ovarian serous cystadenocarcinomas in situ, was fully preserved in the majority of cell lines. The main cytokeratin polypeptides expressed were numbers 7, 8, 17, 18 and 19. The tumor-associated antigen CA-125, but not CEA, was shed in the culture supernatant. This was in accordance with FACScan analysis of the cell lines and the level of CA-125 and CEA in the patients' serum. The estrogen and progesterone receptors were negative both in the cell lines and in the original tumors. These new ovarian carcinoma cell lines will be valuable models for further investigations into a variety of biological properties.

Adult↗
PubMed1992

The tumour-inhibiting potential of the progesterone antagonist Onapristone in the human mammary carcinoma T61 in nude mice.

The progesterone antagonist Onapristone proved to possess strong tumour-inhibiting activity in a panel of experimental mammary carcinomas. Its underlying mechanism of action is due to a progesterone-receptor-mediated induction of terminal differentiation and a specific blockade of the cell cycle and is also present in the absence of progesterone as was shown in the MXT mammary tumour. To prove this further, the tumour-inhibiting activity of Onapristone was investigated in the human postmenopausal T61 mammary tumour implanted in castrated male nude mice. Whereas Onapristone given alone had no effect on growth of established tumours, after stimulation of the relatively low progesterone receptor content of this tumour line with an oestrogen, Onapristone significantly inhibited tumour growth. Thus, we suggest that Onapristone exerts its antitumour action via progesterone receptors. As there is no endogenous progesterone in these mice, the tumour-inhibiting activity of Onapristone is not primarily due to a classical antihormonal effect.

Animals↗
PubMed1992

Dihydrospirorenone (ZK30595): a novel synthetic progestagen--characterization of binding to different receptor proteins.

Dihydrospirorenone (6 beta, 7 beta, 15 beta, 16 beta-dimethylen-3-oxo-17a-pregn-4-en-21, 17-carbolacton) is a new type of progestin with no other agonistic activities, in particular no estrogenic, androgenic or glucocorticoid activity. Dihydrospirorenone is a potent aldosterone antagonist 8 times as potent as spironolactone and antiandrogenic (0.3 times cyproterone acetate). The aim of the present study is to make a broad characterization of dihydrospirorenone at the receptor level and to discuss the results in comparison to those of established progestins. Kinetic studies of 3H-dihydrospirorenone uptake show a rapid increase in the amount of specific binding during the first three hours. The dissociation of 3H-dihydrospirorenone from the cytoplasmic human uterine progesterone receptor, measured by displacement of labeled steroid with dextran-coated charcoal treatment at 4 degrees C at various times, showed a monophasic or one-component, first order dissociation curve like progesterone. Sucrose density gradient centrifugation of the 3H-dihydrospirorenone-labeled myometrial cytosol showed that the dihydrospirorenone binding components sedimented in the 4S and 8S region which is typical for the progesterone receptor under low salt conditions. The high binding affinity of dihydrospirorenone to the binding sites of the mineralocorticoid receptor of rat kidney with an RBA value of 230% compared to aldosterone is remarkable. This reflects the strong antimineralocorticoid activity of this compound which was evaluated in adrenalectomized rats. Furthermore, competitive studies indicated that dihydrospirorenone also displays high affinity for the androgen and some affinity for the glucocorticoid receptors but no measurable affinity for the estrogen receptor.

Androstenes↗
PubMed1991

Pharmacokinetics of droloxifene and its metabolites in breast cancer patients.

Pharmacokinetics and metabolism of droloxifene, a new antiestrogenic drug, have been investigated by single- and multiple-dose studies in postmenopausal patients with advanced breast cancer. Short terminal elimination half-life, low accumulation, and improved drug tolerability are the most striking features of this safe and effective new antiestrogen. Bioequivalence of film-coated tablet, tablet, and standard solution of droloxifene has been shown. The concentrations of droloxifene and its metabolites have been determined by a highly selective HPLC method.

Administration, Oral↗
PubMed1991

[Plasma lipoprotein fractions in high-dose medroxyprogesterone acetate therapy in metastatic breast cancer].

Metabolic disorders induced by synthetic gestagens have been discussed under the aspect of single endocrine parameters or the carbohydrate or lipid metabolism. In order to obtain more complex information a prospective study of 26 patients was performed, who were treated with 1,000 mg medroxyprogesterone acetate (MPA) per day over a period of 5 weeks as a second-line therapy of breast cancer. Before treatment and afterwards once a week the serum concentrations of MPA, androstenedione, DHEA-S, cortisol, prolactin, insulin, c-peptide, glucose, cholesterol, triglycerides, phospholipids and the lipoprotein fractions (VLDL, IDL, LDL, HDL) were analyzed. Besides the reduction of the androgens and changes in the glucose regulation significant effects on the lipoprotein metabolism were observed, leading to the conclusion that under high-dose gestagen therapy very complex interactions of the endocrine and metabolic system occur.

Antineoplastic Agents↗