Search PubMed⌕ Search

Biomedical subjects

G R Merriam

Publications and source records attributed to G R Merriam.

At least 127 records · Page 7Linked to original sources
PubMed1980

Endotoxin-induced uveitis in the rat.

Experimental studies of ocular inflammation induced by endotoxin have been performed almost exclusively in rabbits. Although the rat has been considered refractory to both the systemic and local effects of endotoxin, the present study has shown that intravitreal injection of endotoxin evoked a characteristic acute inflammatory response which was reproducible and dose-dependent. In addition, a consensual ocular response in the control eye occurred which was less severe but also dose-dependent. Preliminary investigations support the view that consensual responses of this nature may be mediated by a nervous reflex are mechanism. Sequential histological analysis revealed a marked polymorphonuclear cell infiltration of most ocular tissues in the early stages, while mononuclear cells predominated after 3 days. Widespread intravascular microthrombi were also observed, particularly in the ciliary vessels. Recovery, however, was usually complete by 7 days.

Animals↗
PubMed1980

Low plasma levels of 2-hydroxyestrone are consistent with its rapid metabolic clearance.

Published plasma levels of the catechol estrogen 2-hydroxyestrone (2-OHE1) are comparable to those of estrone and estradiol. In light of the very high (40,000 L/d) metabolic clearance rate of 2-OHE1, these concentrations imply unreasonable production rates. We therefore re-examined plasma 2-OHE1 levels using a modified radioimmunoassay procedure. Plasma samples are extracted with ethyl acetate and passed over a short column of LH-20 Sephadex before equilibration with an antiserum directed against a 2-hydroxyestrone-17-(O-carboxymethyl)oxime-bovine serum albumin conjugate. Plasma 2-OHE1 concentrations are indistinguishable from blank (< 15 pg/ml) in men and non-pregnant women, but rise to approximately 200 pg/ml during pregnancy. These values for 2-OHE1 levels are consistent with the rapid metabolic clearance of this catechol estrogen.

Adolescent↗
PubMed1980

Comparative properties of the catechol estrogens, I: methylation by catechol-O-methyltransferase and binding to cytosol estrogen receptors.

Five catechol estrogens and two 2-methoxyestrogens were compared for their relative affinity of binding to hypothalamic, pituitary, and uterine cytosol estrogen receptors; and for the kinetics of the catechols' methylation by hepatic catechol-0-methyltransferase. All of the catechol estrogens tested have similar Km's for 0-methylation (9-14 muM). Estrogen receptor affinities, however, differ widely. In hypothalamus, for example, where estradiol-17 beta has a Kd of 0.039 +/- 0.008 nanomolar, 4-hydroxyestradiol also binds tightly (0.12 +/- 0.02 nM), 2-hydroxyestradiol and 4-hydroxyestrone with intermediate affinity (0.26 +/- 0.06 and 0.28 +/- 0.07 nM, respectively), and 2-hydroxyestrone and 2-hydroxyestriol much less well (1.68 +/- 0.79 and 1.27 +/- 0.26 nM, respectively). The binding of the 2-methoxyestrogens is extremely weak. These receptor affinities roughly parallel the potencies of these compounds in altering gonadotropin secretion.

2-Methoxyestradiol↗
PubMed1980

2-hydroxyestradiol-17 alpha and 4-hydroxyestradiol-17 alpha, catechol estrogen analogs with reduced estrogen receptor affinity.

2-Hydroxyest radiol-17 alpha and 4-hydroxyestradiol-17 alpha, the catechol derivatives of estradiol-17 alpha, have reduced affinity for hypothalamic, pituitary, and uterine estrogen receptors, but retain a potency for interaction with catechol-0-methyltransferase equal to that of the natural, 17 beta-hydroxy catechols. This dissociation of receptor binding and catecholamine interactions may allow the use of the 17 alpha catechols as a probe for the mechanism of action of the catechol estrogens.

Amygdala↗
PubMed1980

Adrenocorticotropin deficiency: correction of hyponatremia and hypoaldosteronism with chronic glucocorticoid therapy.

A 36-yr-old woman with a chronic wasting illness associated with hyponatremia and hypotension proved to have secondary adrenal insufficiency and low levels of GH and PRL. TSH, LH, and FSH responses remained normal. Aldosterone excretion was markedly reduced (0.74 microgram/day) before replacement therapy was started, but normal renin and aldosterone responses to sodium restriction were observed after 6 months of corticosteroid treatment. These responses were maintained after acute steroid withdrawal despite the continued absence of ACTH. Chronically adequate glucocorticoid levels were necessary to maintain a normal aldosterone response in this patient. If there is also a pituitary factor required for this response, it does not appear to be ACTH.

Adrenocorticotropic Hormone↗
PubMed1980

Testosterone-estradiol binding globulin binds to 2-methoxyestradiol with greater affinity than to testosterone.

This report describes the unexpected observation that testosterone-estradiol binding globulin (TeBG) binds 2-methoxyestradiol better than it binds either testosterone or 17 beta-estradiol. As determined by competitive displacement of 3H-testosterone from TeBG adsorbed onto a solid phase matrix of Con A-Sepharose, the relative binding activities of 2-methoxyestradiol, testosterone and 17 beta-estradiol for TeBG were 2.0, 1.0 and 0.32, respectively. In contrast, 2-methoxyestradiol, which is known to bind with low affinity to estrogen receptors, had only low affinity binding to the androgen receptor, as determined by competitive displacement of 3H-dihydrotestosterone using 64-24 rat mammary tumor cells. 2-Methoxyestradiol is the first example of a naturally occurring steroid which binds with high affinity to TeBG but with low affinity to both androgen and estrogen receptors.

2-Methoxyestradiol↗
PubMed1980

Rapid metabolic clearance of the catechol estrogen 2-hydroxyestrone.

The plasma metabolic clearance rate (MCRp) of 2-hydroxyestrone was measured in normal young adults by two methods: infusion of unlabeled 2-OHE1 to equilibrium with radioimmunoassay of plasma 2-OHE1 levels, and infusion of [3H]2-OHE1 to equilibrium with measurement of chromatographically purified plasma [3H]2-OHE1. MCR's were 40--70,000 L/day and 15--50,000 L/day, respectively. This is the highest known MCR for a naturally occurring steroid. The only measurable plasma metabolite of [3H]2-OHE1 co-migrated with 2-methoxyestrone. When [3H]2-OHE1 was incubated with blood samples in vitro, [3H] xi-methoxyestrone was rapidly formed. Since this MCR is higher than cardiac output, clearance must occur primarily in the blood compartment, probably largely by the action of erythrocyte catechol-0-methyltransferase.

Adult↗
PubMed1979

Sex-related and cyclic variation of trace elements in rat hypothalamus and pituitary.

The concentrations of 7 trace elements--iron, copper, zinc, arsenic, selenium, bromine, and rubidium--in rat hypothalami and anterior pituitaries were measured by X-ray fluorescence spectrometry. Male, cycling female, and oophorectomized animals were studied under different conditions of reproductive function. Hypothalamic zinc and copper concentrations both rose between proestrus and estrus days and fell again at diestrus. After castration, concentrations of iron, copper, and arsenic were decreased in both pituitary and hypothalamus, while zinc concentrations rose. Male rats had lower pituitary concentrations of iron, copper, zinc, arsenic, and rubidium than cycling females. Under these hormonal manipulations, hypothalamus zinc concentration and gonadotropin secretion appear to be correlated. While injections of copper salts into the hypothalamus can also stimulate gonadotropin release, we did not observe any consistent relation between endogenous hypothalamic copper concentrations and gonadotropins.

Animals↗
PubMed1979

The effect of endotoxin-induced intraocular inflammation on the rat lens epithelium.

Intraocular inflammation induced by an intravitreal injection of Shigella endotoxin into the rat eye produces early changes in the number of dividing cells of the lens epithelium and affects the organization of the meridional rows. A depression in mitotic activity in the germinative zone is observed during the first 24 hr after injection. At 48 hr, despite the continued mitotic inhibition in the germinative zone, an increase in cell division occurs in the central zone. By 72 hr, the germinative zone mitosis reappears and exceeds control values, whereas the central zone mitotic activity returns to normal. At that time mitotic figures are found in the transitional zone. Disorganization of the meridional rows is seen as early as 12 hr after injection (the first time period observed) and reaches a peak by 48 hr. During the next 5 days, however, the severity of the disorganization diminishes. By the seventh day the rows appear, for the most part, fully recovered, and the mitotic activity reaches normal or near-normal levels in all regions. The details of these observations and their possible relationship to inflammatory cataracta complicata are discussed.

Animals↗
PubMed1977

Father-to-son transmission of hypogonadism with anosmia: Kallmann's syndrome.

Gonadal and olfactory features of Kallmann's syndrome, usually considered to be inherited as an X-linked recessive trait, were found in a father and son who both had cryptorchidism, hypogonadism, and hyposmia. The father's fertility had been induced with chorionic gonadotropin, leading to the birth of three children. Olfactory and gonadal functions were normal in the mother and two siblings. The father had low basal plasma testosterone and subnormal follicle stimulating hormone (FSH) response to luteinizing hormone-releasing hormone (LH-RH). The affected son and his healthy brother were prepubertal. Their basal plasma total and free testosterone, serum FSH and luteinizing hormone (LH), and response to LH-RH were similar. The clinical presentation and formal olfactory function studies were considered most helpful for the suggestive diagnosis of Kallmann's syndrome in children. The occurrence of this syndrome in this family is consistent with autosomal dominant inheritance.

Child↗
PubMed1976

Lens epithelium and radiation cataract. I. Preliminary studies.

The migration of epithelial cells during fibergenesis in the lenses of young rats was determined by tritiated thymidine autoradiography. Cells initially labeled in the germinative zone appeared in the lens bow within seven days. Irradiation with either 600 or 2,400 rads of x-rays did not greatly alter the migration rate, but it did interfere with normal differentiation and proper fiber deposition, as manifested by a displacement posteriorly of the lens bow nuclei and an accumulation of abnormal nucleated fibers in the posterior part of the cortex. The presence of labeled cells in those regions prior to the onset of opacification is consistent with the possibility of direct epithelial cell involvement in radiation cataractogenesis.

Animals↗
PubMed1976

Metabolism of diethylstilbestrol by rat liver: a preliminary report.

Aerobic incubation of a misture of E[1,1,1-D3]-3,4;bis(p-hydroxyphenyl)-hex-3-ene admixed with an approximately equimolar amount of unlabeled diethylstilbestrol and [ 2-(14)C ] diethylstilbestrol with rat liver homogenates in the presence of NADPH yielded water-soluble metabolites as well as products more and less polar than the starting material. Addition of 5-adenosyl-L-methionine increased the quantity of nonpolar metabolites. Incubation with rat liver microsomes yielded similar results. When polar metabolites from incubation with rat liver microsomes were incubated with catechol O-methyltransferase and S-adenosyl[methyl-3 H]-L-methionine there was conversion to 3H-labeled nonpolar products. Examination of reaction products by means of gas chronatography-mass spectrometry gave evidence for the formation of a dihydroxydiethylstilbestrol, a dihydroxydienestrol, and a monomethoxydiethylstilbestrol.

Animals↗