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C B Coulam

Publications and source records attributed to C B Coulam.

At least 145 records · Page 8Linked to original sources

Localization of a molecule immunochemically similar to eosinophil major basic protein in human placenta.

We have recently reported that human pregnancy is characterized by a 10- to 20-fold elevation of eosinophil major basic protein (MBP) immunoreactivity in maternal blood. Here we show, by immunofluorescence, that placental tissue specifically binds antibody to MBP in and around the placental X cells and placental-site giant cells and, using thin plastic sections, that placenta has no infiltrating eosinophils. The X cells line the inner aspects of placental septal cysts, and the cyst fluid, obtained by aspiration, contains immunoreactive MBP at concentrations of 100 micrograms/ml, a sixfold greater concentration than the highest levels measured in maternal blood. The soluble MBP immunoreactivities in placental homogenates and in maternal serum chromatograph identically on Sephadex G-50, and both these gestational MBP molecules migrate as though substantially larger than the MBP found in serum from patients with hypereosinophilic syndrome or purified from the eosinophil granule. Our inability to demonstrate eosinophils in maternal blood or placental tissue, coupled with the large quantities of immunoreactive MBP highly localized in placental cysts and the chromatographic behavior of this molecule, suggest that the MBP detected in human gestation is produced by placenta.

Animals↗

Freezing embryos.

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Beginning of Human Life↗

Incidence of ectopic pregnancy in Rochester, Minnesota, 1950-1981.

Trends in the occurrence of ectopic pregnancy from 1950 through 1981 were evaluated in the defined population of Rochester, Minnesota. The average ratio of ectopic pregnancies to live births was 1:171. The ratio declined from 1:141 to 1:217 from 1955-1959 to 1970-1974 and increased sharply to 1:122 by 1975-1980. Similarly, the average age-adjusted incidence rate of ectopic pregnancies per 100,000 women of childbearing age was 49 over the period studied. A peak rate of 79 per 100,000 was reached in 1955 to 1959, and a trough of 30 per 100,000 occurred in 1970 to 1974; this was followed by a sharp increase to 49 per 100,000 in 1975 to 1981. Methods of measuring ectopic pregnancy are contrasted, and possible risk factors are suggested.

Abortion, Induced↗

Androgen receptor in human foreskin. II. Characterization of the receptor from hypospadiac tissue.

Hypospadias represents a spectrum of disorders known as androgen insensitivity syndromes, which are characterized by a nonresponsiveness of an androgen target tissue to the steroid. The basic defect in this disorder is unknown. This article presents results of studies of the androgen receptor with use of human foreskin from normal neonates undergoing circumcision and from patients undergoing urethroplasty necessitated by hypospadias. It is speculated that a defect in receptor level or function might explain this disorder. The androgen receptors from both normal and hypospadiac tissue were stabilized with a buffer containing 50 mM Tris hydrochloride, 1 mM ethylenediaminetetraacetic acid, 12 mM monothioglycerol, 10% (v/v) glycerol, and 10 mM sodium molybdate plus 1 mM phenylmethylsulfonylfluoride (pH 7.5). The receptors were characterized by Scatchard analysis, competitive binding assays, sedimentation analysis, molecular sieve chromatography, and isoelectric focusing techniques. Specific R 1881 binding to soluble proteins from normal human foreskin was shown to be high affinity (dissociation constant = 0.5 nM), low capacity (6 fmol/mg of protein), and steroid specific. Sedimentation analysis by sucrose density gradients demonstrated the 8S-to-4S shift from low- to high-salt treatments. The receptor from the foreskins of hypospadiac patients also contained androgen receptor in a concentration similar to that in the foreskins of normal persons. The affinity for steroid binding and sedimentation profiles or sucrose gradients of the androgen receptor between normal persons and hypospadiac patients were also similar. However, the androgen receptor from hypospadiac patients displayed different patterns of molecular sieve chromatography from those displayed by the receptor of normal persons. The reason for this difference is not known but may reflect a defective receptor and explain the basic mechanism of this disorder.

Androgen-Binding Protein↗

Elevated serum levels in human pregnancy of a molecule immunochemically similar to eosinophil granule major basic protein.

We have shown that serum levels of a molecule immunochemically similar to eosinophil granule major basic protein (MBP) are elevated in pregnant women throughout gestation. MBP levels increase during gestation and plateau at approximately 7,500 ng/ml by the 20th wk (greater than 10-fold above normal). Levels return to normal after delivery, with a T1/2 of 13.7 d. The MBP in pregnancy serum is remarkably similar to the eosinophil granule MBP in that: (a) pregnancy MBP fully inhibits the binding of radiolabeled MBP standard in a double antibody radioimmunoassay; (b) this inhibition reaction is specific for human MBP because pregnancy serum produces no inhibition of the binding of radiolabeled guinea pig MBP in the guinea pig MBP radioimmunoassay; (c) in a two-site immunoradiometric assay for MBP, slopes of dose-response curves for pregnancy serum, purified MBP, and serum from a patient with hypereosinophilic syndrome are identical, and maximal binding is comparable; (d) reduction and alkylation of pregnancy sera increases measured MBP 100-fold, as previously shown for eosinophil granule MBP in serum; and (e) the MBP in pregnancy serum demonstrates the same pattern of heat lability as has been previously reported for MBP. Four observations have raised the possibility that the eosinophil is not the source of the MBP in pregnancy serum: (a) no correlation between serum MBP level and peripheral blood eosinophil count exists in pregnant women, in contrast to previous studies of patients with eosinophilia; (b) levels of three other eosinophil-associated proteins are normal or low in pregnancy sera, whereas the serum levels of these proteins are elevated in patients with eosinophilia; (c) the slopes of dose-response curves for pregnancy sera and MBP standards differ in the double antibody radioimmunoassay; and (d) the molecule in pregnancy serum elutes from Sephadex G-50 columns at the void volume, while eosinophil granule MBP and the MBP in serum of patients with eosinophilia elute at a volume consistent with the previously established molecular weight of 9,300. These findings suggest that the MBP in pregnancy serum is derived from a source other than the eosinophil.

Animals↗

Ultrasonic assessment of subsequent unexplained infertility after ovulation induction.

The development of ovarian follicles was studied ultrasonographically in 21 cycles in eight infertile patients with the diagnosis of ovulatory dysfunction in whom conception did not occur after the defect had apparently been corrected. Pelvic ultrasound demonstrated three patterns in 20 of the 21 cycles studied: ovarian hyperstimulation in seven cycles; follicular atresia before ovulation in three cycles; persistent unruptured follicular cysts in 10 cycles. Recognition of these patterns has been helpful in modifying therapy in infertile patients.

Chorionic Gonadotropin↗

The prevalence of autoimmune disorders among patients with primary ovarian failure.

Eighty-one patients who had a diagnosis of primary ovarian failure were studied to determine its possible association with autoimmune disorders. All 81 patients displayed 46,XX chromosome complements. On ovarian biopsy, either few or no follicles were demonstrated in 79 patients, and, in two patients, primordial follicles were more abundant. The two patients with a large number of primordial follicles had normal function of other endocrine organs; however, 15 of the 79 patients demonstrating few or no ovarian follicles had associated failure of other endocrine glands, and one patient had myasthenia gravis. Thirteen of these 15 patients sought treatment because of secondary amenorrhea, the age at onset ranging from 11 to 34 years. Of the 81 patients, 11 had primary amenorrhea and 70 had secondary amenorrhea. Among the 79 patients with few or no ovarian follicles, endocrine glandular failure, in addition to ovarian failure, was found in two patients with primary amenorrhea and in 13 patients with secondary amenorrhea. The association of polyglandular failure syndrome and primary ovarian failure, along with demonstration of a lymphocytic infiltrate in ovaries and circulating antibodies in sera of women with premature ovarian failure, suggests that an autoimmune mechanism may be a cause of primary ovarian failure in some cases.

Adult↗

T-lymphocyte subsets during pregnancy and the menstrual cycle.

Many observations suggest that cellular immunity is depressed during gestation. To define alterations in subsets of circulating lymphocytes during pregnancy, we compared the percentages of total T cells, T helper cells, and T suppressor cells in the peripheral blood of 31 pregnant women at various stages of gestation with those in that of nonpregnant controls. Control studies consisted of five women ingesting oral contraceptives and five women menstruating spontaneously. Isolated peripheral blood mononuclear cells were reacted with fluoresceinated monoclonal antibodies that were specific for Leu-2 cells, Leu-3 cells, and Leu-4 cells and that were subsequently analyzed on a fluorescence-activated cell sorter. No variation in the percentage of Leu-2, Leu-3, or Leu-4 cells was observed during the menstrual cycle or oral contraceptive cycle. No differences were seen when T-cell subsets at various stages of gestation were compared with the corresponding T-cell subset in nonpregnant controls. The data suggest that pregnancy does not alter the percentage of T-cell subsets in the peripheral blood.

Adolescent↗

Pregnancy following transsphenoidal resection of prolactin-secreting pituitary tumors.

This report describes 200 women in the childbearing age group with prolactin-secreting pituitary adenomas treated by transsphenoidal microsurgery. There were 136 patients with microadenomas (10 mm or less in diameter), 30 with macroadenomas, 11 with invasive adenomas, and one with hyperplasia. The overall rate for postoperative normalization of serum prolactin was 57%, and it was 72% for those patients with microadenomas. Pregnancy was desired by 90 women, and 78 (84%) became pregnant, although 10 required postoperative bromocriptine to do so. Serious postoperative complications were rare, and produced no major morbidity. The results of surgery were most favorable in women with microadenomas and preoperative serum prolactin levels of 100 ng/ml or less.

Adenoma↗

Acanthosis nigricans in a patient with streak gonads.

Acanthosis nigricans (ACN) is associated with ovarian disorders or abnormalities of carbohydrate metabolism. We saw a 21-year-old woman who had primary amenorrhea and ACN. Results of endocrine studies showed anovulation and low serum estradiol levels with increased gonadotropin concentrations. Laparoscopic examination disclosed bilateral streak gonads; the ovaries were completely replaced by fibrous tissue. Cultures of peripheral lymphocytes, skin fibroblasts, and the right and left ovaries demonstrated normal female karyotype 46XX in all mitoses studied. An autoimmune disorder was excluded by the absence of antithyroid and antiadrenal antibodies. Specific antibodies against ovarian proteins were also absent. A glucose tolerance test demonstrated fasting hyperinsulinemia and exaggerated serum insulin response to the glucose load. The observations in this patient exclude a primary pathogenic role for the ovary in the production of ACN; they also lend further support to a connection between the cutaneous disorder and insulin resistance.

Acanthosis Nigricans↗

Chronic anovulation syndrome and associated neoplasia.

Ovarian hormones have been implicated in a number of neoplastic conditions. Chronic anovulation syndrome, a spontaneous biologic experiment of unopposed secretion of estrogen by the ovaries, was identified in a cohort of 1270 patients, and the risk of these patients having neoplasia was studied. Of the 1270 patients studied, 30 had a subsequent malignancy develop; the expected number was 29.8. When the individual types of subsequent malignancy were analyzed, the endometrium was the only site at increased risk. The relative risk of developing carcinoma of the endometrium after the diagnosis of chronic anovulation syndrome is 3.1 (95% confidence interval 1.1 to 7.3). The long-term risk of developing adenocarcinoma of the endometrium might be considered when treating patients who have this syndrome.

Anovulation↗

Comparison of estrogen receptors in human premenopausal and postmenopausal uteri using isoelectric focusing.

Previous studies have suggested that the estrogen receptor in the postmenopausal uterus, although capable of binding estrogen, may be inactive, that is, incapable of translocating and binding to nuclear acceptor sites. The present study uses isoelectric focusing to characterize differences in the estrogen receptor between premenopausal and postmenopausal uterine tissue. Human myometrium (15 premenopausal and ten postmenopausal samples) was examined by isoelectric focusing in the presence and absence of diisopropylfluorophosphate (DFP) and molybdate, which inhibit proteolysis and stabilize the receptor. As demonstrated previously, receptor forms could be identified in two regions of the pH gradient, one in the pH 4 to 5 region and another at pH 6 to 7. When prepared without DFP and molybdate, the percentage of receptors focusing in the pH 4 to 5 range was significantly greater for premenopausal than postmenopausal tissue (P less than .01). The addition of DFP and molybdate significantly altered the focusing pattern of postmenopausal tissue (P less than .01), increasing the percentage of binding in the pH 4 to 5 range. In the presence of DFP and molybdate, the focusing patterns of receptor from premenopausal and postmenopausal tissue were not significantly different. These data suggest that endogenous proteases are more prevalent in postmenopausal tissue and can degrade the receptor to forms that focus at a higher pH. With the inhibition of these proteases, the focusing patterns of receptors in premenopausal and postmenopausal tissue become very similar, representing the undegraded and perhaps native form of the receptor.

Adult↗

The association between pituitary adenomas and chronic anovulation syndrome.

A cohort of 487 patients with chronic anovulation syndrome diagnosed between January 1, 1970, and January 1, 1980, were followed up to determine the frequency of pituitary adenomas among them. Of the 487 patients, four (0.8%) had pituitary adenoma. This compares with an expected number of 0.42, yielding a relative risk of 9.5 (95% confidence interval, 2.6 to 24.3). Within this cohort, the prevalence rate was 2.7% for galactorrhea and 3.3% for hyperprolactinemia. The prevalence rate of abnormal radiologic findings was 6.4% for roentgenography of the sella, 25.4% for sellar tomography, and 14.7% for computed tomography. In addition, 15 patients with pituitary adenomas and 60 control subjects were compared for prior anovulation syndrome. The relative risk of pituitary adenomas for patients with chronic anovulation syndrome in this case-control study was 24.3 (95% confidence interval, 4.9 to 120.6).

Adenoma↗

Comparison of estrogen receptors in human premenopausal and postmenopausal uteri: indication of biologically inactive receptor in postmenopausal uteri.

Analysis of the estrogen receptor (ER) from uteri of premenopausal and postmenopausal patients has largely been limited to quantitation. The present study examined the biologic activity of the receptors with regard to their nuclear binding capacities. A Scatchard analysis of myometrial cytosol indicated high-affinity and low-capacity estradiol binding (Kd = 10(-10 M). A 35% ammonium sulfate fraction of cytosol was characterized for steroid specificity, receptor concentration, isoelectric focusing patterns, and capacity of the ER to bind to nuclear acceptor sites in a cell-free assay. The ER from premenopausal uteri displayed an extensive but saturable binding to the nuclear acceptor sites. In contrast, the postmenopausal ER displayed minimal binding. These cell-free binding differences were supported by tissue culture studies. This difference may be accentuated by the fact that much of the receptor is bound by endogenous estrogen in the premenopausal uterine preparation, which would decrease the subsequent binding of the [3H]ER to nuclear sites. This receptor in the postmenopausal uterus is largely unbound and thus would not compete for nuclear sites. These studies suggest that a significant fraction of the ER in postmenopausal uteri is biologically inactive; for example, it cannot translocate and bind to nuclear acceptor sites. This loss in nuclear binding may represent a change in the ER occurring at menopause as a result of changing endocrine states.

Adult↗

Ultrasonic evidence for luteinization of unruptured preovulatory follicles.

Luteinization of an unruptured ovarian follicle has been reported as a cause of infertility and has heretofore been diagnosed only by direct visualization of the ovarian surface. Four patients who demonstrated defects in ovulation requiring therapy to induce ovulation and who were not achieving desired conception despite apparently adequate treatment were studied with serial pelvic ultrasonic examinations for 17 cycles. Luteinization, characterized by the loss of a clear demarcation of the follicular cyst wall and the presence of intrafollicular echoes, was suspected in each of these cycles by the absence of ultrasonic signs of ovulation--that is, a rapid decrease in follicular size and the appearance of free fluid in the cul-de-sac. Histologic confirmation of a persistent luteinized cyst is presented.

Chorionic Gonadotropin↗