Our recent study determined a difference between preeclamptic and non-preeclamptic patients in platelet potentiation by thrombopoietin (TPO) of reactivity to collagen. The main conclusion was that non-preeclamptic, but not preeclamptic, pregnancy patients' platelets showed significant TPO potentiation at first and third trimesters. Since TPO or B2 Bradykinin platelet receptor levels might influence TPO potentiation, we obtained platelet samples from 187 first trimester pregnant patients prospectively followed through pregnancy. Patients were additionally sampled at third trimester, delivery, and 4 to 6 weeks postpartum. A total of 43 patients, including 11 diagnosed as preeclamptic at third trimester, were sampled at least three different times. We used Western blotting normalized with glyceraldehyde 3 phosphate dehydrogenase as a loading and staining control. There were no significant differences in relative receptor levels between groups or sampling times using repeated measures ANOVA with the mixed model allowing for missing samples. While the mechanism for differences in thrombopoietin potentiation of platelet activation by collagen remains unknown, it may be a first trimester indicator of developing preeclampsia.

To determine whether a difference exists in platelet reactivity to collagen and potentiation by thrombopoietin (TPO) between preeclamptic and non-preeclamptic patients, 187 first trimester pregnant patients were prospectively followed through pregnancy. Citrated blood, drawn at first (<14 weeks estimated gestational age) and third trimesters (>28 weeks), when patients were admitted for delivery, and 4-6 weeks postpartum, was assayed by a Whole Blood Impedance Aggregometer measuring platelet activation by 0.4 mug/ml collagen, +/-10 ng/ml TPO. There was no significant difference in 1st trimester platelet collagen activation by unpaired t-test between groups. Significant TPO potentiation of collagen activation (P<0.05, paired t-test) was observed in non-preeclamptic patients at the first and third trimesters. In contrast, preeclamptic patients' platelets show no significant (P>0.8, paired t-test) TPO potentiation at any time. While the mechanism for this difference in thrombopoietin potentiation of platelet activation by collagen as early as the first trimester is unknown, it may be one of the initiating events in this syndrome.

In the present paper, we report that injection of testosterone propionate (500 microg) during the critical window of rat development (postnatal day 5) induces temporary appearance of aged interstitial cells in developing ovaries (days 7 and 10). Aged interstitial cells showed large size (> or = 12 microm), enhanced androgen receptor (AR) and low estrogen (ER) and luteinizing hormone receptor (LHR) expression. Although normal mature interstitial cells (large size and strong ER and LHR expression) appeared later (day 14), and ovaries of androgenized rats were similar to normal ovaries between days 14 and 35, ovaries of adult androgenized females showed only aged and no mature interstitial cells. Androgenization on day 10 caused the development of aged interstitial cells on day 14, but adult ovaries were normal. Long lasting postnatal estrogenization (estradiol dipropionate for four postnatal weeks) caused in developing and adult ovaries a lack of interstitial cell development beyond the immature state. Immature interstitial cells were characterized by a small size (< or = 7 microm) and a lack of AR, ER and LHR expression. Because the critical window for steroid-induced sterility coincides with the termination of immune adaptation, we also investigated distribution of mesenchymal cells (Thy-1 mast cells and pericytes, ED1 monocyte-derived cells, CD8 T cells, and cells expressing OX-62 of dendritic cells) in developing and adult ovaries. Developing ovaries of normal, androgenized and estrogenized females were populated by similar mesenchymal cells, regardless of differences in the state of differentiation of interstitial cells. However, mesenchymal cells in adult ovaries showed distinct behavior. In normal adult ovaries, differentiation of mature interstitial cells was accompanied by differentiation of mesenchymal cells. Aged interstitial cells in ovaries of androgenized rats showed precipitous degeneration of resident mesenchymal cells. Immature interstitial cells in ovaries of estrogenized rats showed a lack of differentiation of resident mesenchymal cells. These observations indicate that an alteration of interstitial cell differentiation during immune adaptation toward the aged phenotype results in precipitous degeneration of resident mesenchymal cells and premature aging of ovaries in adult rats, and alteration toward immature phenotype results in a lack of differentiation of mesenchymal cells and permanent immaturity of ovaries in adult females.

Cyclin E, a G(1) cyclin serving to activate cyclin-dependent kinase 2, is the only cyclin gene for which alternative splicing leading to structurally different proteins has been described. Different cyclin E proteins are present in tumor tissues but absent from normal (steady) tissues. Cyclin E contributes to the regulation of cell proliferation and ongoing differentiation and aging. Because trophoblast has invasive properties and differentiates into syncytium and placental aging may develop at term, we examined cyclin E protein variants in human placenta. Placental samples were collected from 27 deliveries between 33 and 41 wk and were compared with ovarian cancer (positive control). Both placental and tumor tissues showed seven cyclin E low molecular weight (LMW) bands migrating between 50 and 36 kDa. Placental expression of cyclin E showed certain variability among cases. Lowest cyclin E expression was detected in normal placentas (strong expression of Thy-1 differentiation protein in villous core and low dilatation of villous blood sinusoids). Abnormal placentas (significant depletion of Thy-1 and more or less pronounced dilatation of sinusoids) showed significant increase either of all (early stages of placental aging) or only certain cyclin E proteins (advanced aging). Our studies indicate that a similar spectrum of cyclin E protein variants is expressed in the placental and tumor tissues. Low cyclin E expression in normal placentas suggests a steady state. Overexpression of all cyclin E proteins may indicate an activation of cellular proliferation and differentiation to compensate for developing placental insufficiency. However, an enhanced expression of some cyclin E LMW proteins only might reflect an association of cyclin E isoforms with placental aging or an inefficient placental adaptation.

Previous studies have reported controversial data on estrogen receptor (ER) expression in levator ani muscle. We investigated ER expression in levator ani muscle and fascia and compared it with the expression of progesterone receptor (PR) and androgen receptor (AR). The study included 55 women undergoing surgery for gynecological (asymptomatic, n = 10) or urogynecological conditions (symptomatic, n = 45). The asymptomatic and 21 of the symptomatic women received no hormone replacement therapy (HRT). The remaining 24 symptomatic women received some form of HRT. Biopsies were taken from the levator ani muscle and the overlying fascia, and quantitative measurements of immunohistochemical staining by image analysis were made. None of the levator ani muscle samples showed any evidence of nuclear ER expression in striated muscle fibers, but some cells in the muscular stroma did express ER. However, PR and AR expression was found in both muscle and stromal cells. Levator ani fascia showed nuclear ER, PR, and AR expression to varying degrees. There was a significant increase (p < 0.03) in ER expression in levator ani fascia of symptomatic patients without HRT when compared with asymptomatic age-matched women. The ER expression was significantly lower (p < 0.001) in postmenopausal symptomatic women receiving long-term estrogen replacement compared with age-matched women without HRT. Our data indicate that ER expression is significantly higher in symptomatic women compared with age-matched asymptomatic females. However, long-term estrogenization causes significant decrease of ER expression.

Available data indicate that growth of invasive tumors is enhanced by homeostatic mechanisms of the host involved in normal tissue regeneration and repair. To achieve this, malignant cells may (i) induce degeneration of normal cells at the host-tumor interface, (ii) hybridize in situ with activated host stem cells, required for replacement of lost mature tissue cells, (iii) the resulting malignant/normal cell hybrids may exhibit an antigenic similarity to normal cells, (iv) thereby preventing recognition by the immune system, (v) and exploiting normal mechanisms of tissue regeneration by the host. In addition, primary cancers with allotypic determinants may utilize other homeostatic mechanisms evolved in mammals to promote fetal allograft survival. They may have a potential to grow in another (secondary) host. Novel approaches to cancer prevention and control may depend on a better understanding of the mechanisms by which normal cellular growth are controlled, and hybridization prevented.

The presence of pelvic adhesions is implicated as a significant cause of pelvic pain, bowel obstruction and infertility in women. Laparoscopy has become an invaluable method for the evaluation and treatment of such adhesions. A prospective study was designed to correlate specific findings in the preoperative history and physical examination with the presence of adhesions seen at laparoscopy. Two hundred seventy-three consecutive patients undergoing laparoscopy were analyzed; pelvic adhesions were found in 99 (36.3%). At the time of laparoscopy the only historical predictor found to be associated with adhesive disease was previous pelvic surgery. Physical examination predictors associated with the presence of adhesions were uterine immobility, a right adnexal mass and right adnexal tenderness.