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Biomedical subjects

L A Adams

Publications and source records attributed to L A Adams.

14 recordsLinked to original sources
PubMed1991

Testosterone regulates pro-opiomelanocortin gene expression in the primate brain.

Endogenous opioid peptides such as beta-endorphin, derived from proopiomelanocortin (POMC), have been widely implicated as serving an important role in the neuroendocrine regulation of the primate reproductive axis. In both human and nonhuman primates, POMC neurons are thought to mediate, at least in part, the negative feedback action of sex steroids on GnRH. Sex steroids, such as testosterone, are thought to inhibit GnRH secretion by enhancing the inhibitory activity of beta-endorphin; however, the cellular mechanisms by which steroid hormones regulate the activity of POMC neurons in the primate brain are unknown. In this study, we tested the hypothesis that testosterone stimulates POMC gene expression within the primate brain and that this regulation occurs within a specific subset of POMC neurons residing in the arcuate nucleus of the hypothalamus. We used in situ hybridization to compare cellular levels of POMC messenger RNA in intact (n = 4), castrated (n = 4), and castrated/testosterone-treated (n = 4) monkeys. We report that after castration of the male macaque (Macaca fascicularis), cellular POMC messenger RNA levels decline significantly (P less than 0.05) in neurons within the arcuate nucleus and that this decline is prevented by replacement with physiological doses of testosterone. Moreover, we found that this testosterone-dependent modulation of POMC gene expression is restricted to a small fraction of the numerous POMC neurons located within the most anterior region of the arcuate nucleus in the brain of this primate species. These observations provide evidence that sex steroids regulate expression of the POMC gene in the primate brain.

Animals↗
PubMed1991

Nonsurgical repair of perinasal skin defects.

Immediate reconstruction of full-thickness skin defects after cancer surgery is a commonly accepted surgical principle used to preserve function and minimize cosmetic deformity. Healing by secondary intention, however, offers the advantages of optimal cancer surveillance, simplified wound management, and avoidance of reconstructive procedures with their associated costs and potential complications. Accurate prediction of the course of wound healing, and thereby the final functional and cosmetic result, would allow a rational approach to selection of patients for surgical or nonsurgical repair. We observed 282 patients with full-thickness perinasal (glabella, medial canthus, dorsum, sidewall, tip, ala, philtrum, alar base, and nasolabial fold) skin defects after Mohs' surgery and documented a variety of parameters affecting wound healing, including location, depth, and size of the wound. Patients were examined at intervals, and a final determination regarding cosmesis and function was made at 6 months or later. We conclude that the most important considerations in predicting the final functional and cosmetic result include location by subunit, followed by size and depth of the wound.

Adult↗
PubMed1990

Human pituitary corticotroph adenomas in vitro: morphologic and functional responses to corticotropin-releasing hormone and cortisol.

We examined the direct effects of corticotropin-releasing hormone (CRH) and cortisol on the morphology of cells from 6 functioning human pituitary corticotroph adenomas in culture using both light and electron microscopic morphometry and correlated the structural changes with alterations in adrenocorticotropin (ACTH) release in each case. During incubations lasting 2 or 24 h, ACTH release was increased by CRH and reduced by cortisol. After incubations lasting from 2 to 72 h, light microscopic morphometric analysis showed no significant differences in cell size, nuclear area, cytoplasmic area or nuclear/cytoplasmic ratio between treated and control adenoma cells. Ultrastructural morphometry documented increased cytoplasmic volume density (CVD) of rough endoplasmic reticulum and/or Golgi apparatus and reduced CVD of secretory granules in cells incubated with CRH. There was no consistent change in CVD of endoplasmic reticulum, Golgi apparatus or secretory granules in adenoma cells incubated with cortisol, but in all tumors there were marked filament accumulations indicating a direct effect of cortisol on adenomatous corticotrophs. The changes were similar after 2- and 72-hour exposures. These results indicate that (1) some adenomatous corticotrophs can respond to CRH and cortisol; (2) the morphologic changes observed in cells treated with CRH correlate with increased ACTH release, and (3) accumulation of filaments is the direct effect of cortisol and is associated with reduced ACTH release.

Adenoma↗
PubMed1989

Reducing bedtime tantrums: comparison between positive routines and graduated extinction.

A total of 36 toddlers and preschool children exhibiting bedtime tantrum activity were randomly assigned to one of three groups: positive routines, graduated extinction, or control. Positive routines involved changing the child's bedtime to coincide with when he naturally fell asleep, as well as parent and child engaging in a series of four to seven enjoyable activities before the child being placed in bed. During the treatment period, bedtimes were systematically scheduled earlier such that the child went to bed at the time parents had originally used. Graduated extinction consisted of the parent putting the child to bed and ignoring the tantrum activity for increasingly longer amounts of time throughout the treatment. Children in these two treatment groups had tantrums less frequently and for shorter periods than control subjects during 6 weeks of treatment and during two follow-up observations 3 and 6 weeks after treatment. Although both treatments were more effective than waiting for the child to outgrow this problem, parents of the positive routine group reported significantly improved marital satisfaction, suggesting additional benefits of this treatment strategy.

Behavior Therapy↗
PubMed1988

Testosterone modulates the differential release of luteinizing hormone and follicle-stimulating hormone that occurs in response to changing gonadotropin-releasing hormone pulse frequency in the male monkey, Macaca fascicularis.

Selective elevations of plasma follicle-stimulating hormone (FSH) levels are characteristic of some physiological conditions, such as the early stages of human puberty, and in some disorders of testicular function, such as idiopathic oligospermia. We tested the hypotheses that a slow gonadotropin-releasing hormone (GnRH) pulse frequency favors a selective elevation of plasma FSH and that this is influenced by the circulating steroidal milieu. We administered exogenous GnRH at frequencies of once every 90 min (q 90 min) and once every 240 min (q 240 min) to castrated prepubertal male monkeys who had received either empty (sham) or testosterone (T)-filled Silastic capsules at the time of castration. At the end of each experimental frequency period, mean plasma levels of luteinizing hormone (LH) and FSH were measured. Plasma T levels were also measured. Animals with T implants had plasma levels of this hormone that were in the adult range (approximately equal to 8 ng/ml), whereas those with sham implants had plasma T levels in the prepubertal range (less than or equal to 4 ng/ml). In animals with sham implants, mean plasma FSH levels were markedly elevated at the slower GnRH pulse frequency (39.5 +/- 3.6 ng/ml following GnRH q 240 min compared with 23.7 +/- 2.8 ng/ml following GnRH q 90 min). This selective FSH elevation was not apparent in animals with T implants. Mean plasma LH levels were similar (approximately equal to 8 micrograms/ml) at the two GnRH pulse frequencies, in both T-treated and sham-implanted animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Puberty.

Explore the source record for details and available documents.

Animal Nutritional Physiological Phenomena↗
PubMed1987

Neuroanatomical localization of cells containing gonadotropin-releasing hormone messenger ribonucleic acid in the primate brain by in situ hybridization histochemistry.

Using in situ hybridization histochemistry, we have mapped the anatomic localization of perikarya containing mRNA that codes for GnRH and GnRH-associated protein (GAP) in the forebrain of four male macaques, Macaca fascicularis. DNA oligomers, with sequences complementary to either the GnRH or the GAP portion of the mRNA sequence, were synthesized and hybridized to paraformaldehyde fixed, coronal sections of the basal forebrain and hypothalamus. GnRH mRNA was found in the same population of cells as those containing GAP mRNA. GnRH/GAP mRNA-containing cell bodies were observed consistently in the medial septal nucleus, the diagonal band of Broca, the medial preoptic area, supraoptic nucleus, and ventromedial-infundibular region. We detected the presence of GnRH mRNA and GAP mRNA within the same neuroanatomic regions previously shown to include perikarya containing immunoreactive GnRH. The ventromedial-infundibular region and the medial preoptic region contained the greatest number of GnRH/GAP mRNA-containing perikarya (37.0% and 22.5%, respectively). The diagonal band contained 21.0% and the supraoptic nucleus 13.0% of the cells, while the medial septum contained the fewest number (6.7%). This study demonstrates the feasibility of using in situ hybridization as a strategy to study the developmental and steroidal regulation of GnRH gene expression in the nonhuman primate.

Animals↗
PubMed1986

Suppression of plasma gonadotropins and testosterone in adult male monkeys (Macaca fascicularis) by a potent inhibitory analog of gonadotropin-releasing hormone.

The reduction of circulating levels of gonadotropins and testosterone is of value for the treatment of steroid-dependent neoplasms and the control of fertility. We tested the ability of single and multiple doses of the GnRH antagonist [N-Ac-D-Nal(2)1, D-pCl-Phe2, D-Trp3, D-hArg(Et2)6, D-Ala10]GnRH (GnRH-Ant) to suppress levels of these hormones in intact and castrate adult male cynomolgus monkeys. In Exp I, single injections of the antagonist at doses of 0 (vehicle), 5, 50, 250, and 500 micrograms/kg BW were given to castrate and intact animals. In Exp II, daily injections of antagonist at doses of 0, 50, 100, or 250 micrograms/kg BW were given to intact animals for 21 days. Plasma levels of testosterone, FSH, and LH were determined by RIA, and in intact animals, LH levels were measured by bioassay. In Exp 1, a single injection of 5 micrograms/kg BW or more of GnRH-Ant to castrate animals significantly reduced plasma LH and FSH by 4 h after injection (P less than or equal to 0.01). Nadir levels (40% of preinjection control values) of LH and FSH were reached 8 and 24 h, respectively, after administration of 250 or 500 micrograms/kg BW, and these hormones remained significantly lower than preinjection values over at least 48 h (P less than or equal to 0.05). A single injection of 50 micrograms/kg BW or more of antagonist to intact animals markedly reduced plasma LH and testosterone by 6 h after administration (P less than or equal to 0.05), while 250 or 500 micrograms/kg BW antagonist maintained LH and testosterone levels below 30% (P less than or equal to 0.05) of preinjection values for 24 h. In Exp II, daily injections of 250 micrograms/kg BW antagonist to intact animals resulted in near-castrate levels of plasma testosterone which were achieved by 24 h after the first injection of antagonist and persisted for the ensuing 20 days. Daily injections of 100 micrograms/kg BW or less of antagonist were ineffective in suppressing testosterone. Thus, this potent GnRH antagonist acutely and chronically lowers gonadotropin and testosterone levels in adult male cynomolgus monkeys. By virtue of its inhibitory effect, this antagonist is potentially useful as a therapeutic agent in clinical situations requiring long term suppression of testicular function, such as fertility control, the treatment of steroid-dependent neoplasms, and precocious puberty.

Animals↗
PubMed1979

Cell sorter analysis of carcinogen metabolites in human tissues.

A fluorescence -activated cell sorter (FACS-II) was used to examine biochemical parameters in a heterogeneous population of cultured human lymphocytes. Incubation of cells in the presence of benz(a)anthracene (BA) during culture was employed to induce the enzyme system which metabolizes carcinogens. Carcinogen metabolism was assayed directly by measuring the phenolic metabolites of cells exposed to benzo(a)pyrene (BP). Metabolism of benzo(a)pyrene was measured in single cells and was determined to be greater in the larger cells than in the smaller cells of the cultures. For a given size of cells, the enzyme activity was greater in those exposed to benz(a)anthracene during culture. In some studies, viable cells were first sorted by size and subpopulations assayed for the o-deethylation of the compound, ethoxyresorufin, which measures more specifically the activity of cytochrome P-448. Larger cells had higher levels of enzyme activity than smaller cells in agreement with the direct determinations above. It is possible to measure carcinogen metabolism in other tissues by using the techniques described here.

Aryl Hydrocarbon Hydroxylases↗
PubMed1979

Automatic cell identification and enrichment in lung cancer. II. Acridine orange for cell sorting of sputum.

Fluorescence spectra were obtained from cells from sputum and pleural effusions stained with different fluorescent dyes and fixed by alternate methods. The spectra were referenced to a standard allowing for fluorescence comparisons of unstained and stained cells under various conditions. The metachromasia of acridine orange-stained cells offers nuclear/cytoplasmic differentiation in a single stain; mithramycin and propidium iodide do not. Unstained cells have an appreciable amount of green (546 nm) fluorescence, as does Carbowax in Saccomanno's preservative. Cytoplasm stained with acidine orange also has appreciable green fluorescence. Consequently, cells with much cytoplasm have high total fluorescence. Cytoplasmic fluorescence is negligible with mithramycin or propidium iodide. The metachromasia of acridine orange-stained cells is altered by alcohol and Carbowax levels in fixatives, keeping other factors constant.

Acridine Orange↗
PubMed1979

Automatic cell identification and enrichment in lung cancer. III. Light scatter and two fluorescence parameters.

Two fluorescence parameters and size are used in a flow through system to enrich sputum specimens for cancer cells. Human cells in sputum which are stained with acridine orange show a characteristic distribution of red and green fluorescence from which cancer cells can be localized. The peak enrichment is obtained by selectively sorting cells with the largest values of red and green fluorescence. Cancer cells located in other distribution regions having smaller fluorescence intensities show progressively diminished nuclear and cytoplasmic tinctorial features by Papanicolaou stain, consistent with the decreased intensity of red and green fluorescence.

Carcinoma, Squamous Cell↗
PubMedDate not supplied

Microfluorometric quantitation of size, deoxyribonucleic acid and viral antigenic determinants in cells productively infected with HSV-2.

The interaction of herpes simplex virus type 2 (HSV-2) with the eukaryotic human cell line (HEp-2) was investigated by flow microfluorometric analysis. The three parameters that were quantitated include cell size, deoxyribonucleic acid content and the expression of virus-specific antigens. Productively infected cells are always smaller than uninfected ones, and they resolve into two populations with respect to viral antigenic content. Consistent with viral replication, one of these two populations, displaying a higher viral antigenic content, shows morphologic features characteristic of cell degeneration. On the other hand, the second population, with a relatively lower content of viral antigens, displays morphologic features consistent with increased cell growth. Indeed, microfluorometric measurements of the HSV-2-infected cells with respect to DNA content and expression of viral antigenic determinants resolves four cell populations. Of them, one displays the lowest level of viral antigens with the highest (equivalent to 8N) DNA content, features consistent with transformation. The results demonstrate the great potential of this technique for the detection, separation and quantitation of statistically significant cell populations not otherwise identified and for the analysis of virus-host cell interactions resulting in different pathologic outcomes.

Antigens, Viral↗