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Biomedical subjects

K J Ryan

Publications and source records attributed to K J Ryan.

At least 127 records · Page 7Linked to original sources

Counterimmunoelectrophoresis employing coccidioidin in serologic testing for coccidioidomycosis.

Counterimmunoelectrophoresis, was performed for serologic testing for coccidioidomycosis, employing coccidioidin and spherulin as antigens. Results obtained by counterimmunoelectrophoresis were compared with results obtained by complement-fixation and radial immunodiffusion. Of the 37 sera positive by complement-fixation, 28 were positive by counter-immunoelectrophoresis utilizing coccidioidin, whereas only 11 were positive by counterimmunoelectrophoresis utilizing spherulin (although an additional 14 were positive with counterimmunoelectrophoresis employing spherulin when the quantity of spherulin was increased by 50 to 100%). Thirty-three of these complement-fixation-positive sera were positive by immunodiffusion. Counterimmunoelectrophoresis performed with coccidioidin detected antibodies to C. immitis in all patients who had complement-fixation titers greater than 1:4. When combined with latex agglutination, counterimmunoelectrophoresis utilizing coccidiodin had an 86% correlation with complement-fixation for the detection of positive sera.

Antigens, Fungal↗

Recurrent group C streptococcal tonsillitis in an adolescent male requiring tonsillectomy.

A 15-year-old boy had reported episodes of tonsillitis with group C streptococci over a four-month period. The tonsillitis cleared with antibiotic therapy but was followed by a recurrence within a few days. Tonsillectomy resulted in a permanent cure and group C streptococcus was found in the tonsils. A literature search has failed to reveal similar cases and a brief review of the existing literature is given.

Adolescent↗

The intraovarian sites of androgen and estrogen formation in women with normal and hyperandrogenic ovaries as judged by in vitro experiments.

The status of oocytes, the follicular fluid concentrations of steroids, and the in vitro steroidogenic capacities of stromal tissue, thecal tissue, and granulosa cells from a 15-yr-old girl with primary amenorrhea, ovarian hyperandrogenism, insulin-resistant diabetes mellitus, and acanthosis nigricans were compared to those from normal adult human ovaries. Most oocytes (95%) in the antral follicles recovered from the hyperandrogenic ovaries were degenerative, and the antral fluid levels of testosterone were 30- to 200-fold higher than those in normal ovaries. Granulosa cells from the hyperandrogenic ovaries produced mainly estradiol as did those from normal healthy follicles. The thecal tissues produced 2- to 6-fold more androgen than similar tissues from normal ovaries. However, the stroma from the hyperandrogenic ovaries produced 49- to 250-fold more testosterone than that generated by normal tissues. These data suggest that the removal of stromal tissue as well as follicular tissue from patients with certain types of hyperandrogenism may sometimes contribute to a reduction in androgen secretion.

Adolescent↗

Direct effects of medroxyprogesterone acetate (MPA) and megestrol acetate (MGA) on rat testicular steroidogenesis.

The effects of MPA and MGA on rat testicular steroidogenesis were examined by studying: 1) serum testosterone in hCG primed animals treated with MPA or MGA, 2) testosterone synthesis in rat Leydig cells cultured with MPA or MGA, 3) MPA and MGA binding to rat testis microsomal cytochrome P-450 and 4) MPA and MGA inhibition of enzymes of rat testicular steroidogenesis. In immature rats receiving 1.0 IU of hCG per day 20 mg/kg of MPA or MGA reduced serum testosterone by 57 and 56%, respectively. In mature male rats receiving 50.0 IU of hCG per day 20 mg/kg of MPA or MGA reduced serum testosterone by 40 and 29%, respectively. In rat interstitial cells cultured with 10 ng of rat LH, 1 microM MPA or MGA inhibited testosterone production by 32 and 23%, respectively. Addition of MPA or MGA to microsomal preparations resulted in a type I cytochrome P-450 difference spectrum. MPA and MGA inhibited rat testicular 17 alpha-hydroxylase, 17,20-lyase, and the 3 beta- and 17 beta-hydroxysteroid dehydrogenases. These findings suggest that MPA and MGA inhibit rat testicular steroidogenesis in vivo and in vitro.

Age Factors↗

Response of serum prolactin to catechol estrogen in the immature rat.

The response of serum prolactin to the catechol estrogens, 2-hydroxyestrone (2-OH E1) and 2-hydroxyestradiol (2-OH E2) and their primary estrogens, estrone (E1) and estradiol (E2), was studied in 35-day-old male rats. The subcutaneous administration of 50 microgram of 2-OH E1 or 2-OH E2 significantly suppressed serum prolactin concentrations, but they were not significantly altered by the administration of 50 microgram of E1 or E2.

Animals↗

Induction of labor with anencephalic fetus.

Elective induction of labor, followed by vaginal delivery, was carried out at 25 to 39 weeks' gestation in 14 consecutive patients (15 pregnancies) with an anencephalic fetus. Laminaria tents and prostaglandin drugs were used. The procedures produced no serious untoward effects and required only 3 hospital days.

Abortion, Induced↗

Effects of estrogens on sleep and psychological state of hypogonadal women.

A double-lind crossover study involving 16 hypogonadal women compared the effects of placebo and conjugated estrogens, 0.625 mg daily, on gonadotropin levels, symptoms, sleep patterns, and psychological state. After one month, serum concentrations of follicle-stimulating hormone fell 31%, and levels of luteinizing hormone, 19%; the number of vasomotor flushes also decreased. The administration of estrogens was also associated with a shorter mean sleep latency, a longer period of rapid eye movement sleep, and a positive correlation between psychological intactness (as clinically ranked) and latency to sleep onset. Psychological testing, including the Clyde Mood Scale, and the Gottschalk-Gleser Test indicated that estrogens caused this group to be less outwardly aggressive but more inwardly hostile.

Adult↗

Endocrine studies of normal and polycystic ovarian tissues in vitro.

The purpose of this study was to compare the steroidogenic potential of the granulosa, theca, and medullary tissues from polycystic and normal ovaries. These ovarian endocrine compartments were isolated from appropriate ovaries and were cultured in vitro for three days in the absence (control) and presence of follicle-stimulating hormone (FSH)/luteinizing hormone (LH) (1 lU/ml), N6,O2-dibutyryladenosine-3':5''-cyclic monophosphoric acid (Bu2cAMP) (10(-2)M), and adrenocorticotropic hormone (ACTH) (1.3 U/ml). After the incubation, steroids in the media were measured by radioimmunoassay. Granulosa cells (10(5) cells per dish) from 4 to 7 mm follicles of normal and polycystic ovaries secreted progesterone spontaneously during the culture period and the production of progesterone was markedly stimulated (between tenfold and thirtyfold) by gonadotropins and Bu2cAMP but not by ACTH. Little, if any, androgen (androstenedione, dehydroepiandrosterone, and testosterone) or estrogen (estrone and estradiol) accumulated in the media of any granulosa cell culture. The control cultures of theca tissue from normal and polycystic ovaries secreted large amounts of androstenedione and progesterone and the production of these steroids by normal and polycystic ovary theca was stimulated in most cases by LH/FSH and Bu2cAMP but not by ACTH. Both normal and polycystic ovary theca secreted some testosterone and dehydroepiandrosterone but little, if any, estrone or estradiol accumulated in any theca culture. The medullary tissue of normal and polycystic ovaries produced only trace amounts of steroids in vitro except for the results from one polycystic ovary with hyperthecosis in which case significant quantities of C19 and C18 steroids were secreted. These experiments have demonstrated that isolated granulosa and theca cells from midantral follicles of normal and polycystic ovaries have a similar capacity to secrete C21 and C19 steroids in the absence and presence of trophic agents. Therefore, it seems probable that chronic anovulation in patients with polycystic ovaries is not caused by an obvious deficiency in the de novo steroidogenic potential of the multiple midantral follicles of the polycystic ovaries or by the absence of gonadotropin receptors on the polycystic ovary follicular cells.

Adrenocorticotropic Hormone↗

Clinical applications in the area of contraceptive development.

The ovary is not necessarily a prime locus for regulating reproductive function but in the process of understanding various aspects of ovarian function, opportunities have arisen to test both the role of specific functions in the reproductive process and the possible use of a given function as a site for contraceptive regulation. Better understanding of corpus luteum physiology from receptor site-gonadotropin interaction to natural luteolytic processes still hold promise for contraceptive development.

Contraceptive Agents↗

Metabolism of androstenedione by human ovarian tissues in vitro with particular reference to reductase and aromatase activity.

The ability of granulosa and theca cells of the human ovarian follicle at different stages of development, as well as stromal and luteal tissues from human ovaries to metabolize androstenedione (delta 4) to testosterone (T), dihydrotestosterone (DHT), estrone (E1) and estradiol (E2) with or without exposure to additional amounts of folicle-stimulating hormone was investigated by in vitro experiments. The results show that all the aforementioned ovarian tissues metabolized delta 4 to DHT. Indeed, with the exception of estrogen-secreting granulosa cells from large antral follicle (greater than 10 mm diameter) and possibly also luteal tissue from mid-luteal phase ovaries, the various ovarian tissues preferentially metabolized delta 4 to DHT instead of E (E1 + E2). Although thecal tissue is a major source of delta 4 in human ovaries it is concluded that the granulosa cells do not interact with the theca for the synthesis of E as the follicle enlarges from 1 to 10 mm in diameter. Indeed, excessive thecal delta 4 during this growth phase probably inhibits normal follicular development. However, as the follicle enlarges beyond 10 mm in diameter, and as the granulosa cells begin to preferentially metabolize delta 4 to E, the two cell-types of the follicle may increasingly interact to enhance the follicular output of E.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Danazol binding to rat androgen, glucocorticoid, progesterone, and estrogen receptors: correlation with biologic activity.

Danazol was found to possess androgenic and glucocorticoid activity in rat bioassays. In contrast, danazol displayed no significant estrogenic activity. In support of these findings, danazol bound to the 8 S androgen receptor of rat prostate cytosol and to the glucocorticoid receptor of rat liver cytosol, but danazol did not bind well to the estrogen receptor of the rat uterus. Finally, danazol bound to the progesterone receptor of the rat uterus, but controversy continues as the whether danazol possesses progestational, antiprogestational, or no progestational effects.

Animals↗

Improved antitumor effects in 3'-branched homologues of 2'-deoxythioguanosine. Synthesis and evaluation of thioguanine nucleosides of 2,3-dideoxy-3-(hydroxymethyl)-D-erythro-pentofuranose.

The 3-(hydroxymethyl) branched homologue of 2-deoxyribofuranose was synthesized from the corresponding branched ribofuranose 2-O-(S-methyl dithiocarbonate) with tributyltin hydride in the first direct, one-step deoxygenation at C-2 of a ribofuranose. Nucleoside coupling afforded the corresponding 3'-branched 2'-deoxyribonucleosides of thioguanine. The alpha- and beta-nucleosides were equally inhibitory to growth of WI-L2 human lymphoblastoid cells, were phosphorylated and incorporated into the DNA of Mecca lymphosarcoma in mice to the same degree, and were more effective in these tests than the parent analogue alpha-2'-deoxythioguanosine. These results indicate that the hydroxy functions at the 3' and 5' positions of 2'-deoxynucleosides are interchangeable and that acceptance by the that the furanose ring oxygen and 2'-methylene are corresponding interchangeable, and that acceptance by the enzymes is improved if primary hydroxyls are provided at both the 3' and 5' positions.

Animals↗

Testicular aromatization in immature rats: localization and stimulation after gonadotropin administration in vivo.

Aromatization was measured in testicular microsomal preparations obtained from rats treated 3--4 days with FSH, hCG, or vehicle, hCG, but not FSH, was found consistently to stimulate testicular aromatase activity at least 10-fold. As a marker for FSH action, epididymal androgen-binding protein was assayed and found to be 3 times higher in FSH-treated rats than in either hCG or control rats. hCG, but not FSH or vehicle, stimulated serum testosterone levels more than 100-fold. In all groups, aromatase activity in the microsomal fraction was at least 6 times higher than that found in the mitochondrial fraction. In experiments in which testicular compartments were separated, microsomal preparations from interstitial tissue of hCG-treated rats had 5--7 times more aromatase activity than microsomes from seminiferous tubules and 2--3 times more activity than microsomes from whole testes. It is concluded the hCG administered in vivo can stimulate testicular aromatase activity in immature rats, and the increase in activity is localized in the interstitial tissue.

Animals↗