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Biomedical subjects

G T Ross

Publications and source records attributed to G T Ross.

At least 19 recordsLinked to original sources
PubMed1991

Synthesis of redox derivatives of lysine and related peptides containing phenothiazine or tris(2,2'-bipyridine)ruthenium(II).

Boc-L-Lysine derivatives and lysine-containing peptides bearing the electron donor 10H-phenothiazine (PTZ) or the redox chromophore tris(2,2'-bipyridine)ruthenium(II) dication ([Rub3]2+, where b is 2,2'-bipyridine) have been synthesized and characterized. SeO2 oxidation (53% yield) of 4,4'-dimethyl-2,2'-bipyridine, Ag2O oxidation (85% yield) of the monoaldehyde, complexation (96% yield) of 4'-methyl-2,2'-bipyridine-4-carboxylic acid (m-OH) with Rub2Cl2, activation (81% yield) of the acid [Rub2m-OH]2+ (PF6-)2, and condensation (83% yield) of the succinimido ester [Rub2m-OSu]2+ (PF6-)2 with Boc-Lys furnished the protected redox-chromophore module [Boc-Lys(Rub2m)-OH]2+ (PF6-)2 in 29% overall yield over five steps. The first two steps constitute the first practical synthesis of the monocarboxylic acid m-OH (45% overall yield). Also prepared were m-OSu, Boc-Lys(m)-OH, Boc-Lys(m)-OCH3, and [Rub2m-NHCH3]2+ (PF6-)2. Activation (91% yield) of 3-(10H-phenothiazine-10)propanoic acid (PTZpn-OH) and condensation (92% yield) of the succinimido ester PTZpn-OSu with Boc-Lys furnished the protected electron-donor module Boc-Lys(PTZpn)-OH (84% overall yield). The latter was used in solid-phase syntheses of two redox tripeptides, CH3CO-Ala-Lys(PTZpn)-Ala-OH and [Rub2m-Ala-Lys(PTZpn)-Ala-OH]2+ (PF6-)2. The electrochemical properties of these redox amino acids and peptides were similar to those of PTZpn-OH, [Rub2m-OH]2+ (PF6-)2, or [Rub2m-NHCH3]2+ (PF6-)2. Lys(PTZpn), [Lys(Rub2m)]2+ (PF6-)2, and other redox modules may be useful for engineering light-harvesting proteins, photovoltaic cells, and other molecular electronic devices.

2,2'-Dipyridyl↗
PubMed1982

In vitro conditions affecting the synthesis of sulfated proteoglycans by normal and rheumatoid synovial cells in culture.

In vitro conditions affecting synthesis of sulfated proteoglycans by cell suspensions derived from monolayer cell cultures of normal and rheumatoid synovial tissue were examined. The capacity of cells to synthesize proteoglycans was estimated by the incorporation of 35S--sulfate into cetylpyridinium chloride--precipitable material. Synthesis of sulfated proteoglycans was maximal during log phase, and after 2--3 hours of recovery from disaggregation. Normal synovial cells appeared to be more sensitive to changes in serum concentration than were rheumatoid synovial cells, but rheumatoid synovial cells were more sensitive to changes in cell density. The proportion of newly synthesized extracellular proteoglycans increased with the duration of incubation in 35S--sulfate.

Adolescent↗
PubMed1980

Hormonal regulation of preovulatory follicle maturation in the rat.

Oestrogen-priming of the hypophysectomized immature female rat promotes preantral follicle development in the absence of endogenous gonadotrophins and such as animal is useful for study of the intraovarian glycoprotein-steroidal hormone interactions which underlie morphological and functional development of the ovarian follicle. The present report identifies in vitro the functional characteristics (gonadotrophin binding and steroidogenesis) of granulosa cells harvested at different stages of follicular maturity following treatment with exogenous hormones in vivo. Preovulatory follicle maturation, induced by FSH, has been studied up until antrum formation and the acquisition by granulosa cells of the ability to respond directly to LH or hCG. Before the increases in available granulosa cell membrane LH/hCG receptors associated with the formation of follicular antra, effects of hCG or other hormones with interstitial cell stimulating activity are mediated via interactions with cells outside the lamina basalis. In-vivo studies with oestrogen-primed hypophysectomized immature rats indicate that androgens secreted by LH/hCG-stimulated thecal and/or interstitial cells may act directly on the preantral follicle to promote atresia. However, in-vitro studies have shown a stimulatory effect of androgen on FSH-responsive progesterone secretion by granulosa cells isolated from preantral follicles. These effects, if shown to operate within the ovary during the normal cycle, need not be mutually exclusive because FSH stimulation of granulosa cells in vivo may be a major determinant of follicular responses to androgen. The increase in follicle size and antrum formation accompanying FSH treatment in vivo are associated with (i) increases in the steroidogenic potential of isolated granulosa cells; (ii) the induction of granulosa cell LH/hCG receptors and of steroidogenic responsitivy to hCG; and (iii) stimulation of granulosa cell aromatase activity. These observations highlight the critical role of FSH in the organization of preovulatory follicular morphology and function.

Animals↗
PubMed1980

Clinical relevance of fetal gonadal structure and function.

The foregoing discussion is consistent with the following conclusions: First structural differentiation of the gonads, consonant with chromosomal sex of human fetuses, requires complex interactions of primordial germ cells with coelomic and mesonephric epithelial cells and mesenchymal cells in the genital ridge. The mediators of these interactions remain to be defined. Second, the male fetal gonads secrete substances that direct differentiation of gonaducts and external genitalia along lines consonant with the sex chromosomal constitution. Third, when fetal gonads fail to secrete these substances or target tissues fail to respond, gonaducts or genitalia or both are either phenotypically female or ambiguous, regardless of fetal sex chromosomal constitution. Fourth, although the role of pituitary hormones in gonadal differentiation remains uncertain, the fetal pituitary appears to be required for maintenance of structural and functional integrity of differentiated fetal gonads.

Animals↗
PubMed1979

Production of long term steroid-producing granulosa cell cultures by cell hybridization.

Primary cultures of rat ovarian granulosa cells have been used extensively to study hormonal regulation of cellular function. To date, no long term cultures of ovarian cells which retain their differentiated functions have been developed. Hypoxanthine guanine phosphoribosyl transferase-deficient simian virus 40-transformed rat ovarian granulosa cells were fused with freshly prepared rat granulosa cells using inactivated Sendai virus. Putative hybrid cell strains obtained after selection in medium containing hypoxanthine, aminopterin, and thymidine were analyzed for progesterone synthesis. Neither the original simian virus 40-transformed granulosa cell nor its hypoxanthine guanine phosphoribosyl transferase-deficient derivative produced progesterone, but three of the hybrid strains produced progesterone at basal levels and in response to dibutyryl cAMP. One of these strains produced progesterone in a dose-responsive fashion when exposed to prostaglandin E2, cholera toxin, dibutyryl cAMP, and 2-chloroadenosine. Cell strains obtained by hybridization were remarkably similar to primary cultures of granulosa cells with respect to both the magnitude and temporal aspects of progesterone production in response to dibutyryl cAMP.

Animals↗
PubMed1978

Human chorionic gonadotropin and maternal recognition of pregnancy.

The corpus luteum of the ovulatory cycle is essential for establishing and maintaining the first seven weeks of human pregnancy. Progesterone, given parenterally, appears to be a satisfactory substitute for the corpus luteum, known to be the source of this steroid hormone during this period. Moreover, hCG appears to be essential for sustained secretion of progesterone by the corpus luteum, particularly during the first three weeks after fertilization. In primates at least, neutralization of the biological effects of CG during this critical period results in a reduction of blood progesterone levels and the interruption of pregnancy. Although alternative sources of hCG exist, and the physiological relevance of these sources requires further study, hCG appears to be essential component in the maternal recognition of pregnancy.

Chorionic Gonadotropin↗
PubMed1978

Hormonal correlates of normal and abnormal follicle growth after puberty in humans and other primates.

After the menarche, changing levels of gonadotrophins, prolactin and sex steroid hormones in peripheral blood are accompanied by ovulation and corpus luteum formation in one follicle, and atresia in the remaining follicles maturing during each menstrual cycle. Available evidence suggests that blood levels of steroid hormones reflect in large part the secretory activity of the ovary containing a pre-ovulatory follicle and most probably of that follicle itself (see Chapter 6). These steroid secretions and those of the corpus luteum coordinate hypothalamic-pituitary-ovarian function. Within the ovary, sex steroid hormones mediate effects of gonadotrophins and prolactin on follicle maturation and participate in determining the fate of individual follicles.

Animals↗
PubMed1978

Independence of steroidogenic capacity and luteinizing hormone receptor induction in developing granulosa cells.

The relationship between FSH-induced acquisition of LH/hCG receptors and the steroidogenic capacity of granulosa cells from estrogen-primed hypophysectomized rat ovaries has been examined. Granulosa cells harvested from the immature preantral follicles of animals not treated with FSH (controls) displayed negligible specific human [125I]iodo-hCG binding and produced only minimal amounts of progesterone during 48 h of culture in vitro. Addition of highly purified hFSH or prostaglandin-E2 (PGE2) to the culture medium elicited substantial increases in progesterone production which were not accompanied by measurable increases in [125I]iodo-hCG binding. Treatment with oFSH in vivo for 24 h led to the initiation of antrum formation in many follicles and was accompanied by an 8-10-fold increase in hCG binding by freshly isolated granulosa cells. Basal, hFSH-, and PGE2-stimulated progesterone production during culture was also greater than controls. In contrast, cells from animals receiving oFSH in vivo for only 12 h showed no increase in hCG binding either before or after culture, yet basal and stimulated progesterone production in vitro was significantly greater than controls, indicating that the initiation of steroidogenesis was antecedent to LH/hCG receptor induction. Only those cells obtained after the 24-h in vivo treatment with oFSH produced elevated amounts of progesterone when incubated in the presence of hCG, thereby showing that the observed increases in [125I]iodo-hCG binding reflected the induction of functionally active LH/hCG receptors. Pharmacological stimulation of steroidogenesis by cell suspensions with N,O'-dibutyryl cAMP resulted in consistently high levels of progesterone production irrespective of previous treatment with FSH in vivo. This uniform expression of in vitro steroidogenic capacity occurred in the complete absence of measurable increases in LH/hCG receptors, suggesting that these two fundamental developmental processes are independent phenomena which may be under separate regulation in vivo.

Adenylyl Cyclases↗
PubMed1978

Highly sensitive radioimmunoassay for chorionic gonadotropin in human urine.

The value of RIAs that measure hCG levels in human urine has been limited principally because of cross-reactivity with human LH. Recently, antisera generated to antigenic determinants on the intact hCG beta subunit and its carboxyl-terminal peptide have been shown to exhibit substantially reduced human LH cross-reactivity. To take maximal advantage of these antisera and to minimize interference by nonspecific substances in urine, a procedure for extracting and concentrating hCG from 24-h urine samples was developed. The procedure involves preparation of a standard kaolin-acetone urine concentrate and adsorption of the hCG in the concentrate to Concanavalin A covalently linked to agarose for purification and subsequent RIA. In urine samples obtained from patients with gestational trophoblastic disease, there was a direct correlation between hCG levels measured by RIA and those estimated by mouse uterine weight bioassay. In individual subjects, hCG levels were determined in serum and urine obtained the same day. When hCG was clearly detectable in the serum at levels greater than 1 ng/ml, the quantity of hCG measured in the urine concentrate exceeded 500 ng/24 h. The concentrates prepared from the urine of normal persons contained an hCG-like glycoprotein substance with antigenic determinants similar to those of the carboxyl-terminal peptide of hCG beta. As the range of hCG immunoreactivity measured in the urine concentrates of normal subjects was 6-52 ng/24 h, specific and sensitive detection of urinary hCG could be accomplished in patients whose sera contained hCG undetectable by conventional RIA. Partial purification and concentration of urinary hCG by this procedure with subsequent RIA provides a sensitive and reliable method for detecting hCG in urine.

Antibody Specificity↗