Cytosolic and nuclear progesterone receptors in normal and luteal-phase-defect endometrial cells.

Endometrial biopsies were taken from 93 infertility patients registered in the Reproductive Endocrinology Clinic at the Medical College of Ohio. These endometrial specimens were assayed for nuclear and cytoplasmic progesterone receptors. Only the data from 53 normoprolactinemic euthyroid and nonhirsute patients were considered. Eighteen patients were found to have luteal phase defect by two consecutive out-of-phase biopsies. The remaining 35 patients had in-phase biopsies and were used as controls. Both groups were similar in age and clinical characteristics. Although we noted that the luteal-phase-defect group had fewer nuclear and cytoplasmic progesterone receptors than did the control group, the difference was not statistically significant.

Homologous membrane folate binding proteins in human placenta: cloning and sequence of a cDNA.

A preparation of folate binding protein purified from human placental membranes in the presence of a variety of protease inhibitors followed by deglycosylation with N-glycanase gave a sharp band at Mr approximately 28,000 following SDS-polyacrylamide gel electrophoresis. The deglycosylated protein bound [3H]folic acid as tightly as the native protein. Peptides obtained following digestion of the purified protein with staphylococcal V8 protease and HPLC purification were sequenced. Polyclonal antibodies against the protein preparation were affinity purified and used to screen a placental cDNA expression library. A full-length cDNA for a placental folate binding protein was thus obtained and the corresponding protein sequence deduced. This result, taken together with the peptide sequence data, indicates the expression of at least two homologous folate binding proteins in placenta, one of which appears to be identical with the folate binding protein from human milk and nasopharyngeal epidermoid carcinoma (KB) cells; the cDNA sequence obtained corresponds to the other protein. The deduced protein sequence is characterized by a putative 16-residue amino-terminal signal peptide that is cleaved, resulting in a 239-residue polypeptide. The mature protein exhibits two potential sites for N-linked glycosylation at Asn-99 and Asn-179, eight potential intramolecular disulfide bonds, and a stretch of hydrophobic residues at the carboxyl terminus that could form a transmembrane domain. The protein bears a 68% sequence homology with the KB cell folate binding protein and may represent a fetal folate transport protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Postpartum myocardial infarction in a patient receiving bromocriptine.

A case of a postpartum myocardial infarction in a 27-year-old black multiparous woman is presented. The patient had postpartum pregnancy-induced hypertension in a previous pregnancy. Her most recent pregnancy and immediate postpartum period had been uncomplicated, and she had been sent home with bromocriptine to suppress lactation. Ten days postpartum, she presented with severe hypertension followed by cardiac arrest. Subsequent coronary catheterization revealed no evidence of coronary atherosclerosis but showed a 60-70% stenotic plaque in the left anterior descending artery, possibly secondary to coronary artery spasm. A review of all previously reported cases of postpartum myocardial infarction is presented in an effort to identify the possible etiology of this event and to consider the role of bromocriptine. The most common associated finding in all cases was a history of pregnancy-induced hypertension, which may have been associated with a predisposition to coronary vasospasm. The compounding role of ergot derivatives on vasospasm is considered.

Evolving concepts in the mechanism of steroid action: current developments.

The mechanisms of steroid action remain a poorly understood enigma. Although much effort has focused on the steroid receptor as a mediator of the steroid's effect in the cell, we are only beginning to understand the structure of steroid receptors. Development of monoclonal antibodies directed against both the steroid-binding "receptors" and receptor-associated proteins has allowed novel approaches to the problem. They were important in determining the nucleotide sequences of several receptor genes and subsequently the amino acid sequence of three receptors. Surprisingly, receptors contain amino acid sequences common to v-erb-A, a potentiator of oncogenic transformation. Two receptor-associated proteins have been found and their relationship to the receptors suggests the possibility of additional functions of receptors in addition to binding deoxyribonucleic acid. Thus the role of the receptor in the mechanism of steroid action is evolving from the "two-step mechanism" to one that includes the recently discovered receptor-associated proteins.

A 59-kilodalton protein associated with progestin, estrogen, androgen, and glucocorticoid receptors.

Previous studies of the anti 8.5S progestin receptor monoclonal antibody KN 382/EC1 showed that it was specific for nontransformed progestin receptors. However, with different methods of tissue disruption and the use of protease inhibitors, we found that other nontransformed steroid receptors formed immune complexes with KN 382/EC1. Binding of the antibody to rabbit uterine estrogen, progestin, and androgen and liver glucocorticoid receptor systems was characterized by sucrose density gradient centrifugation, high-pressure liquid chromatography (HPLC), immunoadsorption, and immunoblotting. Immobilized KN 382/EC1 adsorbed both Mr 59,000 and Mr 92,000 proteins. The Mr 92,000 protein appeared to be bound to the antigenic Mr 59,000 protein, and the two proteins were present in apparently the same stoichiometric relationship in several tissues. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of immunoadsorbed material revealed appreciable amounts of both proteins in testis, stomach, lung, liver, uterus, and kidney. Only trace amounts were found in skeletal or heart muscle, and none was found in blood serum. Cleveland digestion of isolated Mr 59,000 and 92,000 proteins revealed dissimilar peptide constituents. Immunoblots of material from uterus and liver resulted in staining of the Mr 59,000 protein but not the Mr 92,000 protein. We conclude that similar antigenic determinants reside in components of several nontransformed steroid receptors and they reside on an Mr 59,000 protein. It is likely, therefore, that there are common components present in nontransformed steroid receptors.

Effects of carbon dioxide and pH on adhesion of Candida albicans to vaginal epithelial cells.

A controlled-environment membrane model for use in vitro was developed and employed in an attempt to mimic the environment of the vagina in order to study yeast-vaginal cell adhesion. Adhesion in vitro of four strains of Candida albicans (NIH 3181A, NIH 526B, ATCC 18804, and MCO 2400) to vaginal epithelial cells (VEC) appeared to be affected by the pH and the level of carbon dioxide that have been found to be present in the vagina in vivo. Strain 3181A had a greater adhesion ability than 526B when the concentration of yeast cells was increased and when the yeast cells were incubated with VEC at pH 5 in sodium phosphate buffer in ambient air supplemented with 10% CO2. Of the four strains of C. albicans used, 3181A had the greatest adhesion ability, with strains 2400, 18804, and 526B ranked in order of decreasing adhesion ability. Also, an enhanced, electron-dense, matted outer region of the cell walls of the yeasts was observed frequently when they were incubated in ambient air supplemented with 10% CO2. In addition, of the vaginal cells that had yeast cells attached to them, an average of 94.4% of the total yeast cells were attached to the microridge side of the VEC, whereas an average of only 5.6% of the total were found on the nonmicroridge side of the VEC. The results from this study indicate that adhesion of C. albicans to the VEC surface was affected by the strain of yeast used, by the side of the vaginal cell exposed, and by the pH and CO2 levels present in the adhesion assay.

A study of fetal acceleration tests.

The fetal acceleration test (FAT) is a means of assessing uteroplacental integrity by observing fetal heart patterns while being stressed by fetal movement. Of 584 tests performed on high-risk obstetric patients, 176 were done within 1 week prior to delivery. Favorable antepartum FAT results correlated with unremarkable initial intrapartum fetal monitor tracings in 128 (97.7 per cent) of 131 cases and also favorable 5 minute Apgar scores (7 to 10) in 128 (97.7 per cent) of 131 cases. An inconclusive FAT correlated with an abnormal OCT or intrapartum monitor tracing in nine of 10 tracings. Two infants with previously abnormal or suspicious FAT, OCT, and intrapartum fetal heart tracings were stillborn. The FAT was also less time-consuming and had fewer complications. These results show the FAT to be an effective clinical test for managing high-risk pregnancies with possible placental insufficiency.

Amniotic fluid analysis in Rh-sensitized pregnancies.

This paper delineates the results of analysis of 234 Rh-sensitized pregnancies. It is now possible to predict the outcome in an Rh-isoimmunized pregnancy based only on the mean amniotic fluid, delta 450. This is an improvement over past methods since it does not depend upon calculation of weeks of pregnancy.

Perinatal infection and vaginal flora.

Vaginal cultures were obtained from 1, 083 mothers on admission to the labor floor. The additional bacteriologic information gained from this survey was not sufficient to warrant continued use of the admission vaginal culture as a screening procedure.

Amniotic fluid phospholipid analysis in normal and complicated pregnancies.

Amniotic fluid lecithin/sphingomyelin (L/S) ratios were determined at least once in 190 pregnancies. In 127 pregnancies an amniotic fluid specimen was obtained within 72 hours of delivery. This constitutes the corrected group. Respiratory distress was encountered 21 times with 13 of these being clinical hyaline membrane disease (CHMD). The remaining cases were either transient respiratory distress or felt to be aspiration pneumonia. When the L/S ratio was positive and the infant delivered vaginally, there was only one case of CHMD. However, when the patients had grave enough disease to warrant cesarean section, CHMD was encountered in seven cases out of 68 cesarean sections. Of the eight cases of CHMD, five were in mothers whose pregnancy was complicated by diabetes mellitus.