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Biomedical subjects

R E Cleary

Publications and source records attributed to R E Cleary.

18 recordsLinked to original sources

The effect of copper in vivo on specific progesterone binding by human endometrial cytosol.

Copper has been shown to interfere with specific progesterone binding by human endometrial and myometrial cytosol in vitro. These results suggested that one possible mode of action of the copper-bearing intrauterine devices (IUDs) is through interference with the action of progesterone at its target sites. A prospective study was carried out to determine whether the proposed mode of action of copper-bearing IUDs could be demonstrated in vivo. The results of this study revealed a significant difference in specific progesterone-binding capacity between proliferative and secretory endometria (P less than 0.001). However, when secretory endometria of the controlled subjects were compared with those of the copper-bearing IUD wearers, no significant difference was observed in the specific progesterone-binding capacity (P greater than 0.2). These data suggested that copper released from copper-bearing IUDs in vivo may not interfere with the binding of progesterone to its receptors in vitro. It is doubtful that the contraceptive effectiveness of copper-bearing IUDs could be due to the ability of copper to prevent progesterone from exerting its full effects on the endometrium.

Adolescent

The Sertoli cell in mixed gonadal dysgenesis.

Since 1937, over 100 cases of mixed gonadal dysgenesis have been described. Thus far, no correlation has been made between the light and electron microscopic morphology of the gonad and the appearance of the ipsilateral internal genitalia. In the case presented in this paper the presence or absence of the Sertoli cell in the ipsilateral gonad correlates with the morphology of the internal genitalia on that side.

Female

Preoperative localization of virilizing tumors by selective venous sampling.

Two postmenopausal patients with virilization had preoperative localization of ovarian tumors by selective blood sampling from both ovarian and adrenal veins and assay of hormone levels. In the first patient, the peripheral concentrations of testosterone (T), androstenedione, and estrone were 936, 1,508 and 73 pg. per milliliter, respectively, levels which are above the ranges found in normal postmenopausal women. The catheterization study showed an increase in the left ovarian vein of all hormones except cortisol. It was predicted that a tumor was present in the left ovary. At operation a 7 by 4 mm. lipid cell tumour was found. In the peripheral blood of the second patient, the T level (4,518 pg. per milliliter) was markedly elevated and the estradiol concentration (73 pg. per milliliter) was increased. At retrograde catheterization the concentration of T in the right ovarian vein was markedly elevated at 120,400 pg. per milliliter. At operation a hilus cell tumor of the right ovary was found. These two cases represent the third and fourth consecutive androgen-secreting tumors from this institution that have been localized by selective ovarian and adrenal vein catheterization and sampling.

Adrenal Glands

Androgen, estrogen, and progesterone by a lipid cell tumor of theovary.

In a 64-year-old woman with a virilizing lipid-cell tumor of the left ovary, serum progesterons, androgens, estrogens, and cortisol levels in the peripheral and ovarian veins were measured. Although virilization was the only symptom of hormone production by the tumor in this patient, endocrine studies showed that several steroids were secreted by this neoplasm. Of the steroids measured, androstenedione was the principal secretory product. Pregnenolone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, dehydroepiandrosterone, and testosterone were also secreted, but in quantities which were one third to one sixth the amount of androstenedione. The tumor's pattern of hormone secretion was similar to patterns of steroid production by ovarian stromal cells found in previously reported in vitro studies. This case and a review of the literature demonstrate that androstenedione appears to be the predominant secretory product of lipid cell tumors, whereas testosterone is the predominant secretory product of hilus cell tumors.

17-alpha-Hydroxypregnenolone

Effect of metal ions on the binding of 17beta-estradiol to human endometrial cytosol.

The influence of zinc and other metal ions on the binding of 3H-17beta-estradiol to human endometrial cytosol was studied. Zn2+ began to interfere with estrogen binding when its concentration in the cytosol exceeded 50 micronM. At a concentration of 5 mM, all of the specific binding of 17beta-estradiol, including more than 50% of the nonspecific binding of the hormone, was destroyed. Analysis of the binding data revealed that one possible site of action of the cations on the binding protein might be the sulfhydryl group(s) of the 17beta-estradiol binding site. The inhibition of 17beta-estradiol binding brought about by Zn2+ was partially abolished by dithiothreitol. Among the metal ions tested, Cu2+ was found to be the most potent inhibitor, followed by Cd2+, Zn2+, and Pb2+. At 1 mM, Mn2+, Ba2+, Ca2+, and Mg2+ had little effect, but at 5 mM, their inhibitory action became more appreciable. K+ and Na+ had no effect on 17beta-estradiol binding. The stimulatory effect of 5 mM Zn2+, Ca2+, Mg2+, and K+ on the binding of 3H-17beta-estradiol to a macromolecular fraction from bovine endometrium was not observed in human endometrial cytosol.

Barium

Dysfunctional uterine bleeding.

Most dysfunctional uterine bleeding is caused by anovulatory cycles. The first step in management is exclusion of local pathology of the reproductive tract, complications of pregnancy or systemic disorders. In the postmenarchal age group, dysfunction of the cyclic center in the hypothalamus is usually present. In the perimenopausal age group, progressive loss of ovarian function leads to anovulation. The age of the patient and the amount of bleeding must be considered when selecting the mode of therapy.

Adolescent

Progesterone binding in human endometrial carcinomas.

By means of dextran-coated charcoal assay, the capacity of various endometrial cytosol preparations for specific binding of 3H-rone was determined. With the use of an arbitrary value of 50 femtomoles of bound 3H-progesterone per milligram of cytosol protein as the breaking point between high and low binding capacities, 19 out of 20 normal endometria had high progesterone-binding capacities. Two out of 11 Grade I, 3 out of 8 Grade II, and 2 out or 4 Grade III endometrial carcinomas showed low binding capacities. All 4 endometrial polyps, 7 out of 9 hyperplastic endometria, and 0 out of 7 nonendometrial gynecologic tumors had high binding capacities. These data suggest a progressive loss of specific progesterone-binding activity from normal endometria to hyperplastic endometria, and from the well-differentiated to the anaplastic forms of endometrial adenocarcinoma. There seemed to be an inverse relationship betweeen age and concentration of progesterone receptors in endometrial adenocarcinomas. All irradiated tumors studied had low progesterone-binding capacity.

Adenocarcinoma

Ureteral obstruction owing to endometriosis: reversal with synthetic progestin.

A case of unilateral ureteral obstruction owing to extensive pelvic endometriosis is presented. There was complete resolution of ureteral obstruction following treatment with synthetic progestin. Sequential assessment of renal function was provided by renal imaging and renograms. It would appear that selected patients with obstructive uropathy may respond favorably to medical management, which would allow for preservation of reproductive capabilities and restoration of renal excretory function.

Adult

Adequacy of vitamin B6 supplementation during pregnancy: a prospective study.

This prospective study assesses the effect of 2.5, 4, and 10 mg of pyridoxine supplementation during pregnancy on maternal and fetal plasma levels of pyridoxal 5'-phosphate (PLP) and on the degree of coenzyme saturation (activation factor) of aspartate aminotransferase and alanine aminotransferase (alphaEGOT and alphaEGPT) in maternal erythrocytes. More than 4 mg of pyridoxine supplementation daily was required for most pregnancies to maintain maternal plasma PLP levels within the range observed during the first trimester and in the nonpregnant state. The plasma PLP concentrations in maternal and cord blood were highly correlated and indicated a dependence of fetal vitamin B6 nutrition on maternal circulating PLP. Measurements of alphaEGOT and alphaEGPT were not as reproducible as plasma PLP assays and were less sensitive and quantitative indicators. In the majority of subjects, the changes in alphaEGOT and alphaEGPT with time correlated poorly with the changes in plasma PLP. However, when the data were analyzed without regard for their dependence on time, they demonstrated a negative, linear correlation between alphaEGOT and log plasma PLP and between alphaEGPT and log plasma PLP for the group on 2.5 mg of pyridoxine and for all the subjects combined. Finally, the dietary records showed that most of the subjects consumed less than 2 mg of vitamin B6 daily from their food. The results indicate that the current Recommended Dietary Allowance for vitamin B6 during pregnancy (2.5 mg) is too low and that supplementation of this vitamin in an amount more than 4 mg daily is recommended.

Alanine Transaminase

Sequential changes in the renin--angiotensin--aldosterone systems and plasma progesterone concentration in normal and abnormal human pregnancy.

To investigate the role of components of the renin-angiotensin-aldosterone system and plasma progesterone concentrations in the pathophysiology of hypertension in pregnancy, sequential measurements were made throughout pregnancy in 45 normotensive subjects, 41 other pregnant patients in whom hypertension became manifest only during pregnancy and 26 patients with chronic hypertension antedating pregnancy. Among the normotensive subjects plasma renin activity and substrate, plasma aldosterone and progesterone concentrations were elevated as early as the sixth week of gestation. While consistent, progressive, further increases were noted in renin substrate, aldosterone and pregesterone concentrations during pregnancy, plasma renin activity did not continue to rise. In both hypertensive groups, plasma renin activity and aldosterone concentration were significantly suppressed during the last trimester despite levels of renin substrate and progesterone that were not significantly different than those observed in normotensive pregnancy. These observations confirm earlier studies reporting suppression near term of plasma renin activity in toxemia and indicate from these prospective observations that they are secondary effects. These studies, in addition, demonstrate parallel suppression of plasma aldosterone concentration in toxemia. The current report also indicates that this suppression is not due to a decrease in renin substrate concentration and that a hypothesized deficiency of plasma progesterone, which was not observed in the hypertensive subjects, does not play a permissive role in the development of hypertension.

Aldosterone

A simplified surgical approach to the incomplete form of testicular feminization.

A simplified surgical approach to the intersex child with the incomplete form of testicular feminization is presented. The procedure is particularly useful in patients where the gonadal tissue is located in the scrotolabial folds and eliminates the necessity for exploratory laparotomy. Representative drawings of the procedure are shown.

Androgen-Insensitivity Syndrome

Ultrastructure of an ovotestis in a case of true hermaphroditism.

A case of true hermaphroditism with bilateral ovotestes is reported. The karyotype was 46, XX. At laparotomy done at the age of 21 months a uterus, bilateral fallopian tubes, and bilateral gonads were observed. On frozen section examination, each gonad was shown to be an ovotestis. By light and electron microscopy, the only cellular abnormality observed in the ovotestes was the absence of primitive germ cells in the seminiferous tubules. The ovarian portion showed primordial follicles and normal follicular development.

Disorders of Sex Development

Maternal and fetal plasma levels of pyridoxal phosphate at term: adequacy of vitamin B6 supplementation during pregnancy.

The effect of different amounts of vitamin B6 supplementation during pregnancy on maternal and fetal plasma levels of pyridoxal phosphate (PLP) at term has been studied. Ten of 13 subjects given 2 to 2.5 mg. of vitamin B6 daily exhibited plasma PLP levels lower than 4.7 ng. per milliliter (the lower limit of normal for nonpregnant subjects). In contrast, only 4 of 11 subjects given a supplement of 10 mg. of vitamin B6 daily had plasma PLP less than this value. The mean plasma PLP level (64.4 ng. per milliliter) of 10 cord blood samples from newborn infants whose mothers exhibited plasma PLP levels greater than 4.7 ng. per milliliter was significantly higher (P less than or equal 0.005) than that (34.2 ng. per milliliter) from 14 newborn infants whose mothers had abnormally lowered plasma PLP concentrations. In cord plasma, an average venous-arterial gradient of 10.6 ng. per milliliter was observed, indicating that the fetus retains and/or degrades PLP. These results suggest that more than 2 to 2.5 mg. of vitamin B6 supplement daily is required for most pregnancies to restore normal vitamin B6 nutrition in the mother and, perhaps, also in the fetus.

Adult

Prenatal sex detection with endocervical smears: successful results utilizing Y-bodyfluoroscence.

Highly equivocal results, regarding procedures for the prenatal detection of fetal sexls found in the endocervix, are reported in the literature dating from 1971. The far-reaching genetic and obstetric implications of such procedures led us to investigate endocervical smears from 36 patients (taken during all three trimesters) and study the validity and practicality of this test. Fetal sex was correctly predicted in 31 of 36cases and all 18 male predictions delivered males. In addition, many previously reported and newly found sources of error were encountered and evaluated. It is concludedthat there are indeed cells of fetal origin being shed into the endocervix and they canbe used as a reliable indicator of fetal sex in all three trimesters.

Cervix Uteri

The effect of lergotrile on galactorrhea and gonadotropin secretion.

Lergotrile (Compound 83636), a specific inhibitor of prolactin release, was administered to 5 women with galactorrhea. Only 1 of the 5 had an elevated serum prolactin (hPRL) value, but Compound 83636 induced a decrease in serum hPRL in all cases. All patients had cessation of breast secretion within 72 days after initiation of lergotrile. LRH administration (100 pg) evoked a variable gonadotropin response before and during treatment with the ergot alkaloid. By contrast, serum prolactin values remained essentially unaltered after injection of LRH under the same conditions.

Acetonitriles