Search PubMed⌕ Search

Biomedical subjects

B R Carr

Publications and source records attributed to B R Carr.

At least 91 records · Page 5Linked to original sources
PubMed1988

Starting the new patient on oral contraceptives.

There are many considerations prior to starting a patient on oral contraceptives (OCs). A careful history and physical examination should be obtained, as should laboratory studies where indicated. In addition to the absolute and relative contraindications to OCs, the benefits should be reviewed with the patient. During therapy, the patient should be advised regarding potential minor side effects as well as serious signs and symptoms. There appears to be little difference in efficacy or side effects of monophasic vs. multiphasic contraceptives. It is recommended that a pill containing the lowest hormonal content, and thus with the least potential for side effects (ie, 35 micrograms of ethinyl estradiol), be utilized.

Adolescent↗
PubMed1988

Peripheral relaxin levels during pregnancy in a woman with homozygous familial hypobetalipoproteinemia.

A case of a normal pregnancy conceived spontaneously in a 22-year-old woman with hypobetalipoproteinemia evidenced peripheral levels of relaxin in the range of uncomplicated singleton pregnancies in conjunction with low peripheral levels of progesterone. The establishment and maintenance of uterine quiescence in this hypoprogestational pregnancy may be attributable to these "normal" relaxin concentrations or to local uterine factors, including decidual relaxin production, which would not be reflected in circulating relaxin levels.

Adult↗
PubMed1987

Ontogeny of adrenal steroid hydroxylases: evidence for cAMP-independent gene expression.

Total RNA from normal and anencephalic human fetal adrenals was examined by blot analysis for transcripts encoding P-450scc, P-450(11) beta, P-450(17) alpha, P-450C21 and adrenodoxin using bovine cDNA clones specific for these different enzymes. The specific contents of RNA encoding these components of the adrenocortical steroidogenic pathway were found to be similar in both types of adrenal tissue. Likewise, immunoblot analysis showed comparable concentrations of P-450scc, P450(17) alpha and adrenodoxin protein to be present in adrenal tissues from normal and anencephalic human fetuses. Immunoblot analysis of homogenates of fetal sheep adrenals of increasing gestational age (85-145 days) showed constant levels of P-450scc and P-450(11) beta, but increasing P-450(17) alpha content, especially near term. Both sheep fetuses prior to 136 days gestational age and human anencephalic fetuses are known to have extremely low circulating levels of immunoreactive ACTH as well as very low adrenal adenylate cyclase activity. Thus, it is concluded that factors other than pituitary ACTH which operate independent of adenylate cyclase activation are required for the initial expression (imprinting) of steroid hydroxylase genes.

Adenylyl Cyclases↗
PubMed1987

Metabolism of lipoproteins by human fetal hepatocytes.

The rate of clearance of lipoproteins from plasma appears to play a role in the development of atherogenesis. The liver may account for as much as two thirds of the removal of low-density lipoprotein and one third of the clearance of high-density lipoprotein in certain animal species and humans, mainly by receptor-mediated pathways. The purpose of the present investigation was to determine if human fetal hepatocytes maintained in vitro take up and degrade lipoproteins. We first determined that the maximal binding capacity of iodine 125-iodo-LDL was approximately 300 ng of low-density lipoprotein protein/mg of membrane protein and an apparent dissociation constant of approximately 60 micrograms low-density lipoprotein protein/ml in membranes prepared from human fetal liver. We found that the maximal uptake of [125I]iodo-LDL and [125I]iodo-HDL by fetal hepatocytes occurred after 12 hours of incubation. Low-density lipoprotein uptake preceded the appearance of degradation products by 4 hours, and thereafter the degradation of low-density lipoprotein increased linearly for at least 24 hours. In contrast, high-density lipoprotein was not degraded to any extent by fetal hepatocytes. [125I]Iodo-LDL uptake and degradation were inhibited more than 75% by preincubation with low-density lipoprotein but not significantly by high-density lipoprotein, whereas [125I]iodo-HDL uptake was inhibited 70% by preincubation with high-density lipoprotein but not by low-density lipoprotein. In summary, human fetal hepatocytes take up and degrade low-density lipoprotein by a receptor-mediated process similar to that described for human extrahepatic tissues.

Binding Sites↗
PubMed1987

The binding and metabolism of low-density lipoprotein by skin fibroblasts of fetuses and newborns with anencephaly.

We have previously demonstrated that the fetus with anencephaly is hypercholesterolemic. The plasma levels of total cholesterol and low-density lipoprotein cholesterol are threefold greater than those of normal fetuses. We have provided evidence that elevated low-density lipoprotein cholesterol levels were caused by reduced uptake and metabolism of low-density lipoprotein by atrophic adrenal glands deficient in low-density lipoprotein receptors. The purpose of the present investigation was to determine if other tissues, namely, skin fibroblasts, of the fetus with anencephaly were also deficient in low-density lipoprotein receptors. We compared the binding and metabolism of low-density lipoprotein by skin fibroblasts of fetuses with anencephaly and normal subjects. Cultures of skin fibroblasts were grown to confluency. Thereafter, the medium was changed to lipoprotein-deficient serum for 24 hours. The rate of uptake and degradation of iodine 125-iodo-LDL was determined as a function of time and concentration of low-density lipoprotein. The maximal specific binding of low-density lipoprotein was also determined. The rate of uptake, degradation, and the maximal binding of low-density lipoprotein was similar in skin fibroblasts of infants with anencephaly and normal subjects. We conclude that the elevated level of low-density lipoprotein cholesterol in cord blood of fetuses with anencephaly is not caused by deficiency of low-density lipoprotein receptors and metabolism in skin fibroblasts but instead by deficiency of low-density lipoprotein receptors and metabolism by atrophic adrenal glands.

Adrenal Glands↗
PubMed1987

Are we exploiting the infertile couple?

We hope that this article brings into focus some problems that merit consideration and debate. These thoughts come from a group of individuals who are actively engaged in reproductive endocrine/infertility practices with special interests ranging from ovulation induction to IVF to laser surgery. As a group, we practice in all parts of the country, and the problems mentioned are not restricted to any individual or region. We urge that all of us be candid with ourselves and our colleagues about what we can and cannot do for the infertile couple. We suggest that gynecologists ask themselves this question and proceed when the answer is affirmative: "Is this procedure really in the patient's best interest?"

Advertising↗
PubMed1987

Treatment of refractory infertility by transcervical intrauterine insemination of washed spermatozoa.

One hundred thirteen couples with either male factor, cervical factor, endometriosis, or idiopathic infertility of at least 3 years' duration were treated by intrauterine insemination (IUI) of washed motile sperm. Of the 68 women who became pregnant or completed at least three cycles of insemination, the overall pregnancy rate was 38.2%, with a mean of 1.7 treatment cycles per pregnancy. The average pregnancy rate per treatment cycle was 11.4%. Women who did not become pregnant underwent an average of 4.7 treatment cycles. Importantly, only two pregnancies occurred independent of treatment in 113 couples. In the male factor group, the pregnancy rate was 42.9% (n = 21). In women with a cervical factor, 34.5% became pregnant (n = 29); in idiopathic infertile couples or women suffering from endometriosis, there was a pregnancy rate of 38.9% (n = 18). The presence of sperm antibodies in either the male or female partner significantly lowered the pregnancy rate (6.7%) when compared with couples without sperm antibodies (50.0%). The authors conclude from these observations that IUI with washed sperm is a successful mode of therapy, especially in the case of males with asthenozoospermia.

Female↗
PubMed1987

The role of calmodulin antagonists on steroidogenesis by fetal zone cells of the human fetal adrenal gland.

The adrenal gland of the human fetus (HFA) is relatively large compared to that of the adult and exhibits an extremely high rate of steroidogenesis both in vivo and in vitro. The fetal zone cells make up 80-85% of the volume of the HFA and are the major site of steroid production during fetal development. We have recently demonstrated that calcium is involved in the regulation of steroidogenesis in fetal zone cells of the HFA. There is considerable evidence that many actions of calcium within cells are mediated by the calcium-binding protein calmodulin. The purpose of the present investigation was to determine if calmodulin also plays a role in HFA steroidogenesis. To investigate this possibility, the fetal zone was dissected from fetal adrenals of first and second trimester human abortuses. After collagenase digestion of the tissue, dispersed fetal zone cells were maintained in a Krebs-Ringers medium at 37 C for a 3-h incubation. Cells were incubated with and without ACTH (10(-8) M) in the presence of the calmodulin inhibitors trifluoperazine (TFP), chlorpromazine (CPZ), and calmidazolium (CAL) at concentrations of 5-100 microM. The media were assayed for contents of dehydroepiandrosterone sulfate (DS), cortisol (F), pregnenolone, and cAMP by RIA. The addition of ACTH stimulated F secretion 5- to 10-fold compared to that in control fetal zone cells. DS secretion increased up to 5-fold and pregnenolone about 2-fold in the presence of ACTH compared to values in control cells. ACTH also stimulated cAMP secretion by 10-fold compared to that in control cells. The addition of TFP, CPZ, and CAL significantly inhibited ACTH-stimulated DS, F, and pregnenolone secretion in a dose-related fashion to near-control levels. We observed that TFP, CPZ, and CAL inhibited cAMP accumulation as well as Bu2cAMP-stimulated steroid secretion. The metabolism of 22R-hydroxycholesterol to pregnenolone was inhibited by TFP and CPZ, but not by CAL. These studies suggest that calmodulin plays a role in regulating steroidogenesis in fetal zone cells of the HFA.

Adrenal Glands↗
PubMed1987

5 alpha-reduced androgens in the human fetal testis.

The androgen content was measured in testes from 34 male and in ovaries from 30 female embryos that varied in age from less than 12 to approximately 20 weeks. The 5 alpha-reduced androgens dihydrotestosterone and 3 alpha-androstanediol were found in testes at a level of about a 30th of that of testosterone at all ages examined, whereas very little or no testosterone, androstenedione, or either of the 5 alpha-reduced androgens were detected in the ovaries. Whether dihydrotestosterone plays a role in the development of the testes is unknown.

Androstane-3,17-diol↗
PubMed1987

The effects of dexamethasone and anencephaly on newborn serum levels of apolipoprotein A-1.

Since the control of production and clearance of plasma lipoproteins in utero is largely unknown, we sought to evaluate the effects of glucocorticosteroid (dexamethasone) treatment of developing fetuses and of chronic intrauterine hypercholesterolemia, due to fetal anencephaly, on newborn serum levels of apolipoprotein A-1 (Apo A-1), the major apoprotein of high density lipoproteins (HDL). Among preterm newborn infants (26-32 weeks gestation), the total, HDL, and low density lipoprotein cholesterol levels in umbilical cord serum of 11 newborns exposed to 4 doses of dexamethasone (5 mg each) within 1 week of delivery [mean, 3.05 +/- 1.01 (+/- SD), 0.83 +/- 0.18, and 1.84 +/- 0.69 mmol/L, respectively] and of 3 anencephalic newborns (2.84 +/- 0.57, 0.83 +/- 0.36, and 1.89 +/- 0.54 mmol/L) were increased to a similar extent over those in 17 normal newborns (1.76 +/- 0.16, 0.62 +/- 0.16, and 1.14 +/- 0.13 mmol/L). On the other hand, umbilical cord serum Apo A-1 levels were markedly increased only in the dexamethasone-treated preterm newborns (1.35 +/- 0.55 g/L; anencephalic, 0.78 +/- 0.15 g/L; normal, 0.68 +/- 0.06 g/L). Also, whereas serum total, HDL, and low density lipoprotein cholesterol levels in 5 term anencephalic newborns (3.85 +/- 1.37, 1.06 +/- 0.08, and 2.64 +/- 0.91 mmol/L) were substantially higher than those in 41 normal term newborns (1.42 +/- 0.28, 0.57 +/- 0.12, and 0.74 +/- 0.05 mmol/L), serum Apo A-1 levels were similar at term in anencephalic (1.01 +/- 0.30 g/L) and normal newborns (0.99 +/- 0.08 g/L). Normal Apo A-1 and lipoprotein cholesterol levels were found in an additional newborn who was delivered 30 days after exposure to dexamethasone. We conclude that intrauterine glucocorticosteroid treatment leads to transiently increased serum Apo A-1 levels in the newborn. This increase, however, is not likely to be secondary consequence of the hypercholesterolemia that also occurs in such newborns, since hypercholesterolemia of a similar extent in anencephalic newborns, who have atrophic adrenals, was not associated with marked changes in serum Apo A-1 levels.

Anencephaly↗
PubMed1986

Prostaglandin secretion by adrenal tissue of human anencephalic fetuses.

Previously we reported that the human fetal adrenal gland secreted various prostaglandins and that prostaglandin secretion was inhibited by endogenously synthesized glucocorticoids. Furthermore, we reported that the neocortex secreted larger quantities of prostaglandins than did fetal zone tissue and that the pattern of secretion of prostaglandins of the two zones differed. In the present investigation the rate and pattern of prostaglandin secretion by adrenal tissue of anencephalic fetuses were assessed and compared to either whole or separated zones of human fetal adrenal tissue. The rate of prostaglandin secretion into the culture medium was determined by measuring prostaglandin E2 or prostaglandin F2 alpha with use of specific radioimmunoassays in media collected at 24-hour intervals. The rate of prostaglandin E2 secretion by adrenal glands obtained from two anencephalic fetuses declined rapidly from 1.71 +/- 0.65 ng/mg-1 of protein per 24 hours and 0.82 +/- 0.46 ng/mg-1 of protein per 24 hours on day 1, respectively, to 0.36 +/- 0.03 and 0.12 +/- 0.04 ng/mg-1 of protein per 24 hours by the fifth day in culture. The rate and pattern of prostaglandin F2 alpha secretion by anencephalic tissue was similar to that of prostaglandin E2. The pattern of prostaglandin secretion by anencephalic adrenal tissue was similar to that observed in neocortex tissue, but the rate of prostaglandin secretion was less. When the rates of prostaglandin secretion by anencephalic and neocortex adrenal tissue were compared to the rates of secretion of cortisol, an inverse relationship was observed. Finally, when whole human fetal adrenal glands or anencephalic tissues were incubated in the presence of adrenocorticotropic hormone, dexamethasone, metyrapone, or SU 10603, the data obtained seemed to suggest that the rate of prostaglandin secretion was regulated in both tissues by endogenously synthesized glucocorticosteroids. In summary, the pattern of secretion of prostaglandins by the anencephalic adrenal gland was similar to that of neocortex tissue, and the rate of secretion of prostaglandins was inhibited by endogenously synthesized cortisol.

Adrenal Cortex↗
PubMed1986

The effect of spironolactone on aromatase activity.

Spironolactone, an aldosterone antagonist, causes decreased plasma testosterone (T) levels and gynecomastia in men and is clinically useful in the treatment of hirsutism in women. Many mechanisms of action for spironolactone have been proposed. It has been suggested that one cause for low plasma T levels may result from an increased metabolic clearance rate of T due to increased extraglandular aromatization to 17 beta-estradiol. The purpose of this investigation was to determine the effect of spironolactone on the rate of activity of aromatase in human fetal liver (hFL) cells. The activity of aromatase was assayed by determining the rate of incorporation of [1-3H]androstenedione into [3H]water in hFL cells exposed to spironolactone (10(-10) to 10(-4) M) for 24 or 72 hours. The aromatase activity in control hFL cells remained constant during the study. Dibutyryl cyclic adenosine monophosphate significantly stimulated aromatase activity from 63 to 257 pmol X mg-1 protein X 2 hours-1 after 24 hours and 72 hours exposure, respectively. In contrast, when hFL cells were exposed to spironolactone (10(-10) to 10(-5) M) for up to 72 hours, the activity of aromatase did not differ significantly from that in control hFL cells. It is concluded that spironolactone in therapeutic concentrations does not stimulate aromatase activity in hFL cells maintained in vitro.

Aromatase↗
PubMed1986

Prolactin levels in umbilical cord serum and its relation to fetal adrenal activity in newborns of women with pregnancy-induced hypertension.

The effect of hypertension in pregnant women on fetal maturation is an issue of considerable importance. Because of a possible role of prolactin in fetal adrenal steroidogenesis and in fetal lung maturation, we have investigated the relationship between hypertension in pregnant women and levels of prolactin and dehydroepiandrosterone sulfate in serum of newborn infants. It was found that with the mild-to-moderate form of pregnancy-induced hypertension (PIH), there was little effect on prolactin levels in newborn serum. In newborns of women with severe PIH, however, serum prolactin levels were significantly greater (p less than 0.01) than those in newborns of women with uncomplicated pregnancies. Conversely, umbilical serum concentrations of dehydroepiandrosterone sulfate in newborns of women with severe PIH were significantly less (p less than 0.05) than those in newborns of women with uncomplicated pregnancies. These findings are supportive of the view that pituitary function and adrenocortical function of fetuses of women with PIH are different from those of fetuses of normotensive women. These findings are suggestive that PIH alters the function of the fetal pituitary and adrenal cortex.

Adrenal Glands↗
PubMed1986

Human fetal liver estrogen 16 alpha-hydroxylase: precursor specificity, kinetic parameters, and in vitro regulation.

The properties of human fetal liver (HFL) estrogen 16 alpha-hydroxylase (16 alpha-OHase) were studied in microsomal preparations and hepatocytes maintained in culture. A specific assay was developed for the determination of estrogen 16 alpha-OHase activity based on the enzymatic release of tritium from the C-16 alpha position of stereospecifically labeled 16 alpha-3H-labeled C18-steroids, viz. 17 beta-[16 alpha-3H]estradiol, 17 beta-[16 alpha-3H]estradiol 3-sulfate, [16 alpha-3H]estrone, and [16 alpha-3H]estrone sulfate. The percentage of tritium at the C-16 alpha position of 17 beta-[16 alpha-3H]estradiol was 92.5%. There was no kinetic isotope effect in the 16 alpha-hydroxylation of 17 beta-[16 alpha-3H]estradiol. HFL hepatocyte and microsomal 16 alpha-OHase activity was linear with incubation time for at least 2 h, with a hepatocyte number up to 6.7 X 10(6) cells/ml and a microsomal protein concentration up to 1 mg/ml. The apparent Km of 16 alpha-OHase for estrone sulfate (E1S) was greater than that for either 17 beta-estradiol (E2) or estrone (E1; 2.9-6.4 microM vs. 0.70-0.84 microM). The maximum velocity of HFL 16 alpha-OHase also was greater with E1S or 17 beta-estradiol 3-sulfate than with either E1 or E2, and E1S was the most efficient substrate. The apparent temperature optimum for the microsomal enzyme was 37 C, and the apparent pH optimum was 7.0. 16 alpha-Hydroxylation of E1S by HFL microsomes was inhibited noncompetitively by E1. The biosynthesis of estriol from E2 by fetal liver microsomes does not require an intermediate oxidation step of E2 to E1 as appears to be the case in vivo in the human adult; this was demonstrated by the formation of [17 alpha-3H]estriol from [17 alpha-3H] E2 in incubations with HFL microsomes. A number of growth factors, hormones, and xenobiotics were preincubated with hepatocytes for 24 or 72 h to test for stimulation/inhibition of 16 alpha-OHase activity. 16 alpha-OHase activity was stimulated by dexamethasone, forskolin, (Bu)2cAMP, cholera toxin, 1,2-benzanthracene, and phenobarbital. Diethylstilbestrol, E2, and progesterone did not alter hepatocyte 16 alpha-OHase activity, except when very high concentrations of E2 and progesterone were used, when they became inhibitory; other hormones and growth factors did not alter the basal levels of the enzyme.

Anencephaly↗
PubMed1986

Adenylate cyclase activity in membrane fractions of adrenal tissue of human anencephalic fetuses.

There is greater basal and ACTH-stimulated adenylate cyclase activity in membrane fractions prepared from the neocortex of human fetal adrenal (HFA) tissue than in similar preparations from the fetal zone. In this study, the specific activity of adenylate cyclase was determined in membrane preparations of adrenal tissue obtained from anencephalic fetuses (n = 5) varying in gestational age from 17-43 weeks. The basal adenylate cyclase activity in membrane fractions of adrenals of anencephalics was 2.9 +/- 2.1 (mean +/- SEM) pmol mg protein-1 min-1, 3-5% of the average specific activity in membrane preparations of fetal zone or neocortex of normal fetuses. ACTH (10(-10)-10(-4) M) in the incubation mixture stimulated adenylate cyclase activity 2- to 5-fold in whole HFA membrane fractions. In contrast, ACTH, when added to adrenal membrane preparations of the anencephalics, did not stimulate adenylate cyclase activity. Furthermore, sodium fluoride or forskolin stimulated adenylate cyclase activity markedly in HFA membrane preparations of normal fetuses, but did not affect enzyme activity in adrenal membrane preparations of the anencephalics. In conclusion, the basal activity of adenylate cyclase in adrenal membrane preparations of anencephalics was low and unresponsive to brief exposure to ACTH, sodium fluoride, or forskolin. These findings as well as those of our previous investigations suggest that the expression of HFA adenylate cyclase may be regulated in part by ACTH.

Adenylyl Cyclases↗
PubMed1986

Estrogen 16 alpha-hydroxylase activity in human fetal tissues.

Estrogen 16 alpha-hydroxylase activity was measured in microsomes prepared from fetal tissues of first and second trimester human abortuses using [16 alpha-3H]estrone sulfate as substrate and NADPH as cofactor. Estrogen 16 alpha-hydroxylase activity was demonstrable in 13 of 14 fetal tissues examined in this study, viz. liver, adrenal fetal zone, adrenal neocortex, lung, kidney, intestine, heart, brain, skin, testis, spleen, pancreas, and stomach, and was either negligible or absent in placental tissue. The highest specific activity of the microsomal enzyme [pico-moles of product(s) formed per mg protein/h] was found in liver (mean +/- SEM, 338 +/- 62), and the next highest was found in the fetal zone of the adrenal cortex (70 +/- 20). The specific activities of estrogen 16 alpha-hydroxylase in adrenal neocortex, brain, skin, and testis were similar (25-53 pmol/mg protein X h) as were those in lung, kidney, intestine, heart, spleen and stomach (23-36 pmol/mg protein X h). The specific activity of the enzyme in the pancreas was 12 pmol/mg protein X h; the lowest specific activity, however, was in placental microsomes (0.2 +/- 0.1 pmol/mg protein X h).

Adrenal Glands↗