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Biomedical subjects

R B Barnes

Publications and source records attributed to R B Barnes.

12 recordsLinked to original sources
PubMed1992

Detection of functional ovarian hyperandrogenism in women with androgen excess.

BACKGROUND: Distinguishing between ovarian and adrenal causes of androgen excess may be difficult. We have found that women with the polycystic ovary syndrome have supranormal plasma 17-hydroxyprogesterone responses to the gonadotropin-releasing hormone agonist nafarelin. We determined the usefulness of testing with nafarelin to distinguish ovarian causes of hyperandrogenism in women. METHODS: We studied 40 consecutive women with hyperandrogenism who had oligomenorrhea, hirsutism, or acne. All 40 underwent testing with nafarelin, dexamethasone, and corticotropin with measurement of circulating concentrations of gonadotropins and steroid hormones, and 19 underwent ovarian ultrasonography. RESULTS: The plasma 17-hydroxyprogesterone response to nafarelin was supranormal in 23 of the 40 women (58 percent), and the plasma androgen response to corticotropin was elevated in 23; 13 women had both abnormalities. Only one woman had conclusive evidence of a steroidogenic block; she had nonclassic adrenal 21-hydroxylase deficiency. Of the 23 women with abnormal responses to nafarelin, only 11 (48 percent) had elevated base-line serum luteinizing hormone concentrations. Of the 13 women with abnormal responses to nafarelin who underwent ultrasonography, 7 (54 percent) had polycystic ovaries. Peak plasma 17-hydroxyprogesterone concentrations after nafarelin administration correlated closely with plasma free testosterone concentrations after dexamethasone administration (r = 0.75, P less than 0.001). CONCLUSIONS: Approximately half of women with oligomenorrhea, hirsutism, or acne have an abnormal response to the gonadotropin-releasing hormone agonist nafarelin, suggesting an ovarian cause of their androgen excess.

17-alpha-Hydroxyprogesterone↗
PubMed1990

Dysregulation of cytochrome P450c 17 alpha as the cause of polycystic ovarian syndrome.

Polycystic ovarian syndrome (PCOS) appears to be due to a previously unrecognized type of steroidogenic abnormality, one in which hyperandrogenism arises from a regulatory abnormality (dysregulation) rather than from enzyme deficiency. It appears that PCOS typically arises from masculinized regulation of the androgen-forming enzyme (cytochrome P450c17 alpha) within ovarian thecal cells. This may arise by either excessive stimulation by luteinizing hormone (LH) or by escape from desensitization to LH. We review evidence which is compatible with the concept that the latter situation may result from an intrinsic intraovarian flaw in the paracrine feedback mechanism by which thecal androgen biosynthesis is inhibited and that coexistent adrenal 17-ketosteroid hyper-responsiveness to corticotropin (ACTH) may be due to a similar type of dysregulation of adrenocortical P450c17 alpha.

Adrenal Cortex↗
PubMed1990

Quantitative and qualitative tests for urinary luteinizing hormone. Comparison in spontaneous and clomiphene-citrate-treated cycles.

A study was performed to evaluate conditions in which false-positive and -negative predictions of ovulation occur with qualitative urinary luteinizing hormone (LH) tests. Three urine specimens and a serum sample were collected daily for LH determination from five anovulatory women treated with clomiphene citrate and from six spontaneously cycling women. The urinary LH was determined with one quantitative and three qualitative tests, and the serum LH was determined with a quantitative assay. Ovulation was determined with transvaginal ultrasound and a serum progesterone level on day 22 of the menstrual cycle. There were six ovulatory and five anovulatory cycles. In those 11 cycles the qualitative urinary LH tests were falsely positive twice and falsely negative thrice. All the false-positive and -negative tests except for one occurred when the quantitative urinary LH was 24-28 mIU/mL. Two false-positive tests occurred one to two days after clomiphene administration. Two false-negative tests occurred in a cycle in which follicular development appeared suboptimal, and one occurred in a cycle with a brief urinary LH surge.

Clomiphene↗
PubMed1989

Pituitary-ovarian responses to nafarelin testing in the polycystic ovary syndrome.

To investigate the basis of polycystic ovary syndrome, we examined the responses of patients to nafarelin, a specific gonadotropin-releasing-hormone agonist, given to stimulate pituitary and gonadal secretion. We compared 16 normal women in the follicular phase, 5 normal men, 8 women with polycystic ovary syndrome, and 1 woman with polycystic ovary syndrome caused by a 3 beta-hydroxysteroid dehydrogenase deficiency. After 100 micrograms of nafarelin was given subcutaneously, serum follicle-stimulating hormone and luteinizing hormone increased rapidly to peak levels within four hours. The women with polycystic ovary syndrome had a pattern similar to that of the men, with greater early luteinizing-hormone responses (30 minutes to 1 hour) and lower peak follicle-stimulating-hormone responses than normal women (P less than 0.05). Patients with polycystic ovary syndrome responded to gonadotropin stimulation with normal to increased production of plasma estrogens and increased levels of androstenedione at 16 to 24 hours (P less than 0.05). Elevated production of 17 alpha-hydroxyprogesterone was found in all the women with polycystic ovary syndrome and in the men. These abnormal responses were unchanged by pretreatment with dexamethasone to suppress adrenal function. In the patient with the 3 beta-hydroxysteroid dehydrogenase deficiency, both basal and stimulated plasma levels of delta 5-3 beta-hydroxysteroids before the enzymatic block were elevated, whereas plasma levels of 17 alpha-hydroxyprogesterone and androstenedione--the steroids immediately beyond the block--were low. We conclude that women with polycystic ovary syndrome have masculinized pituitary and ovarian responses to stimulation by nafarelin. Our findings suggest that the regulation of the ovarian 17-hydroxylase and C-17,20-lyase activities is abnormal in such women.

3-Hydroxysteroid Dehydrogenases↗
PubMed1989

Early differentiation of retinal ganglion cells: an axonal protein expressed by premigratory and migrating retinal ganglion cells.

A monoclonal antibody, RA4, was developed that recognizes retinal ganglion cell axons in the mature retina. Between embryonic days 3 and 9, the RA4 antigen was associated with cell bodies in certain regions of the retina in addition to the ganglion cell axons. The RA4-positive cells were of 3 types: an apolar cell adjacent to the ventricular surface, a bipolar cell that spanned the thickness of the retina, and a monopolar cell in the ganglion cell layer. Evidence suggests that these cells are premigratory and migrating retinal ganglion cells. The expression of the RA4 antigen is the earliest indicator of ganglion cell differentiation yet reported. The existence of RA4-positive apolar cells along the outer surface of the retina suggests that the ganglion cell phenotype is expressed as soon as the cell becomes postmitotic. Approximately 20% of the migrating ganglion cells were in pairs. The paired cells most likely arose from the terminal division of a germinal cell. One possibility suggested by these data is that a ganglion cell-specific germinal cell arises from a pluripotent germinal cell. Immunoblots and other analyses revealed the RA4 antigen to be a 140 kDa cytoplasmic protein in the retina. RA4 also recognized many long tract axons in the brain. In the brain, the RA4 epitope was observed on proteins with at least 7 different molecular weights. Evidence suggests that different cell types may express the RA4 antigen with slightly different molecular weights.

Animals↗
PubMed1987

Correlation of transabdominal and transvaginal ultrasound measurements of follicle size and number with laparoscopic findings for in vitro fertilization.

This paper compared the use of a transvaginal scanning approach with the conventional transabdominal scanning method. In study I, 15 patients with previous suboptimal abdominal ultrasounds were evaluated in subsequent cycles with both the transabdominal and the transvaginal techniques. With the transvaginal method, improvement was observed in 13 patients (87%). Study II compared both the transabdominal and transvaginal ultrasound measurements of follicle number and size with surgical findings. A high correlation (r = 0.914, P less than 0.001) was demonstrated between the number of follicles visualized by transvaginal sonogram and the number of follicles aspirated. A significant correlation (r = 0.639, P less than 0.001) was also observed between follicular fluid volume and the mean ultrasound follicle diameter determined transvaginally.

Female↗
PubMed1985

Dose-related changes in LH bioactivity with intranasal GnRH agonist administration.

In order to evaluate changes in bioactive (bio) and immunoreactive (i) LH and in FSH after intranasal administration of a GnRH agonist, two doses (125 micrograms and 250 micrograms) of nafarelin acetate were administered for 14 weeks to 7 normal women. Maximum changes in gonadotropins were observed 2-4 hours after both the first and last doses. However, the maximum acute responses of iLH, bioLH and FSH were significantly reduced after 14 weeks of treatment while no changes occurred in the bio: iLH ratio. The decrease in these acute responses were not dose-related. Serum iLH and FSH levels obtained prior to each dose (baseline) were not significantly altered by 14 weeks with either dose. However, baseline serum bioLH was significantly reduced compared to pretreatment by 14 weeks but only with the 250 micrograms dose (p less than 0.05). This level was also significantly different from the level of bioLH achieved with 125 micrograms (p less than 0.05). The bio: iLH ratio was also significantly decreased with the 250 micrograms dose. Although serum estradiol and progesterone levels suggested ovarian follicular activity and luteinization with the 125 micrograms dose, this did not occur with 250 micrograms of intranasal nafarelin. These data support a dose response effect of intranasal agonist treatment on the bioactivity of LH and also suggest the relevance of measurements of bioLH in assessing the effectiveness of agonist therapy.

Administration, Intranasal↗
PubMed1985

Comparison of lipid and androgen levels after conjugated estrogen or depo-medroxyprogesterone acetate treatment in postmenopausal women.

Thirty-five women who had undergone a natural or surgical menopause were randomized to receive either 0.625 mg of conjugated estrogen to be ingested for 25 days each month or 150 mg of depo-medroxyprogesterone acetate intramuscularly every three months. Plasma lipids were determined before and after one year of therapy. Serum androgens were measured before and after six months of therapy. Conjugated estrogens and depo-medroxyprogesterone acetate had similar effects on plasma lipids. Cholesterol was decreased (P less than .02 for conjugated estrogen therapy and P less than .01 for depo-medroxyprogesterone acetate therapy), as was low-density lipoprotein cholesterol (P less than .02 for conjugated estrogen and P less than .05 for depo-medroxyprogesterone acetate). Conjugated estrogens also significantly increased high-density lipoprotein cholesterol (P less than .02). High-density lipoprotein cholesterol levels were unchanged after depo-medroxyprogesterone acetate therapy. Serum androgens were generally unchanged after depo-medroxyprogesterone acetate or conjugated estrogen therapy. The data from this study suggest that long-term conjugated estrogen and depo-medroxyprogesterone acetate treatment have similar effects on lipid and androgen levels except that high-density lipoprotein cholesterol was not significantly increased by depo-medroxyprogesterone acetate.

Adult↗
PubMed1978

Quantum yield and image contrast of bacteriochlorophyll monolayers in photoelectron microscopy.

The photoelectron quantum yield spectrum of bacteriochlorophyll aGg (Bchl a ) from Rhodospirillum rubrum was determined in order to evaluate the possibility of mapping photoreceptor distribution and organization in bacterial chromatophores. The quantum yield is on the order of 1 X 10(-3) electrons/incident photon at 180 nm and decreases to 2.5 X 10(-5) electrons/incident photon at 230 nm. Photoelectron micrographs confirm the high contrast predicted between monolayers of Bchl a against a lipid background (calcium arachidate). A significant contrast difference is found between the two monolayer orientations, demonstrating that photoelectron microscopy is a sensitive detector of asymmetry in Bch1 a monolayers.

Bacteriochlorophylls↗