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Biomedical subjects

D L Russell

Publications and source records attributed to D L Russell.

At least 19 recordsLinked to original sources
PubMed2001

Relation of acanthosis nigricans to hyperinsulinemia and insulin sensitivity in overweight African American and white children.

OBJECTIVES: Acanthosis nigricans (AN) has been proposed as a reliable marker of hyperinsulinemia, but its utility for predicting hyperinsulinism has not been systematically evaluated in overweight children. We examined the relationship of AN to hyperinsulinemia and body adiposity. STUDY DESIGN: One hundred thirty-nine children underwent physical examination for AN, body composition studies, an oral glucose tolerance test, and a hyperglycemic clamp. RESULTS: Thirty-five children (25%) had AN. AN was more prevalent in African Americans (50.1%) than in white subjects (8.2%, P < .001). Independent of race, children with AN had greater body weight and body fat mass (P < .001); greater basal and glucose-stimulated insulin levels during oral glucose tolerance test (P < .001); greater first-phase, second-phase, and steady-state insulin levels (P < .001); and lower insulin sensitivity (P < .001) during the hyperglycemic clamp. After adjusting for body fat mass and age, none of these differences remained significant. When categorized by fasting insulin, 35% with fasting insulin levels > 20 microU/mL and 50% with fasting insulin levels > 15 microU/mL did not have AN. Eighty-eight percent of children with fasting insulin levels > or = 15 microU/mL had a body mass index SD score > or = 3.0. CONCLUSIONS: AN is not a reliable marker for hyperinsulinemia in overweight children. Children with a race-, sex-, and age-specific body mass index SD scores > or = 3.0 should be screened for hyperinsulinemia, whether or not they have AN.

Acanthosis Nigricans↗
PubMed2001

Estimation of body fatness by air displacement plethysmography in African American and white children.

The purpose of this study was to determine the ability of air displacement plethysmography (ADP) to estimate body fatness in prepubertal and early pubertal African American and white children. One hundred nineteen nonoverweight and overweight boys (N = 56) and girls (N = 63), age (mean +/- SD) 9.8 +/- 1.7 y, body mass index 25.9 +/- 7.6 kg/m2 (range, 14.2-47.0 kg/m2), and mean percent body fat (%BF) by dual-energy x-ray absorptiometry (DXA) 39.2 +/- 11.7% (range, 12.2-57.5%), were studied. %BF by ADP was compared with DXA %BF estimates and with body fat by several field methods: skinfold thicknesses using the Slaughter et al. equations (Hum Biol 60: 709-723, 1988), bioelectrical impedance analysis (BIA) using the Houtkooper et al. equation (J Appl Physiol 72: 366-373, 1992), and a predictive equation using skinfold thicknesses, BIA, and weight (Goran et al.: Am J Clin Nutr 63: 299-305, 1996). All methods used to estimate %BF were significantly correlated with DXA (all p < 0.0001), with r2 ranging from 0.85 (skinfold measurements) to 0.95 (ADP). ADP using the Siri equation underestimated %BF by -1.9% (p < 0.001); the Bland-Altman limits of agreement (defined as +/-2 SD) were +/-7.4%. %BF by ADP-Siri underestimated %BF by DXA by 3.0% for girls (p < 0.001) and by 0.6% for boys (NS). Agreement between body fat estimation by ADP and DXA did not vary with age, race, or pubertal stage. Application of the age-adjusted Lohman model to ADP significantly increased the magnitude of the underestimation to -6.9% (p < 0.0001). Prediction of %BF by the Slaughter skinfold thickness equation showed no significant mean bias for the overall data, but significantly underestimated %BF in girls (-3.7%) while overestimating %BF in boys (+2.4%) with wide limits of agreement (+/-17.7%, p < 0.01 versus ADP). %BF by the Houtkooper BIA equation or Goran model underestimated %BF to a significantly greater degree than ADP (Houtkooper, -8.1%; Goran, -10.1%; both p < 0.0001 versus DXA or ADP). Determination of %BF from ADP using the Siri model slightly underestimates %BF as determined by DXA in girls, but appears to be superior to existing field methods both in accuracy and limits of agreement. Because of the ease with which it can be performed, ADP may prove useful for investigations of adiposity in children.

Adipose Tissue↗
PubMed2000

Progesterone-regulated genes in the ovulation process: ADAMTS-1 and cathepsin L proteases.

Ovulation is a precisely timed process by which a mature oocyte is released from an ovarian follicle. This process is initiated by the pituitary surge of luteinizing hormone (LH), is temporally associated with transcriptional regulation of numerous genes, and is presumed to involve the synthesis and/or activation of specific proteases that degrade the follicle wall. The progesterone receptor (PR), a nuclear receptor transcription factor, is induced in granulosa cells of preovulatory follicles in response to the LH surge and has been shown to be essential for ovulation, because mice lacking PR fail to ovulate and are infertile. Using these mice as a model in which to elucidate PR-regulated genes in the ovulation process, we show that the matrix metalloproteinases MMP-2 and MMP-9 are not targets of PR during ovulation. In contrast, two other proteases, ADAMTS-1 (A disintegrin and metalloproteinase with thrombospondin-like motifs) and cathepsin L (a lysosomal cysteine protease), are transcriptional targets of PR action. ADAMTS-1 is induced after LH stimulation in granulosa cells of preovulatory follicles and depends on PR. Cathepsin L is induced in granulosa cells of growing follicles by follicle-stimulating hormone, but the highest levels of cathepsin L mRNA occur in preovulatory follicles in response to LH in a PR-dependent manner. The identification of two regulated proteases in the ovary, together with their abnormal expression in anovulatory PR knockout mice, suggests that each plays a critical role in follicular rupture and represents a major advance in our understanding of the proteolytic events that control ovulation.

ADAM Proteins↗
PubMed2000

Ovarian expression of a disintegrin and metalloproteinase with thrombospondin motifs during ovulation in the gonadotropin-primed immature rat.

Mammalian ovulation is a dynamic process that requires degradation of the collagenous connective tissue in the thecal layers of a mature follicle. In this reverse transcription-polymerase chain reaction differential display study, gonadotropin-primed immature rats were used to detect ovarian expression of a relatively new type of disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-1) that is known to cleave extracellular matrix in acutely inflamed tissues. Immature Wistar rats were primed with 10 IU eCG s. c., and the temporal pattern of expression of the ADAMTS-1 gene was delineated by extracting ovarian RNA at 0, 2, 4, 8, 12, and 24 h after induction of ovulation by injecting the primed animals with 10 IU hCG s.c. The differential display data, Northern analyses, and in situ hybridization micrographs all showed significant up-regulation of ADAMTS-1 gene expression by 8 h after hCG administration. The in situ data indicated that the ADAMTS-1 mRNA was in the granulosa layer of mature follicles. Expression reached a peak at 12 h and remained elevated at 24 h after hCG. ADAMTS-1 gene expression was impaired by the antiprogesterone agent epostane, but this inhibition could be overcome by exogenous progesterone. ADAMTS-1 expression was not affected when ovulation was blocked by treatment of the animals with the anti-eicosanoid agent indomethacin. In conclusion, the temporal pattern of expression of this gene, and its apparent regulation by progesterone, suggests that ADAMTS-1 has a significant role in the inflammatory events of the ovulatory process.

ADAM Proteins↗
PubMed2000

Expression of regulator of G-protein signaling protein-2 gene in the rat ovary at the time of ovulation.

The ovulatory process in mammals begins when an endogenous surge in LH circulates to the ovary and couples with receptors in the plasma membranes of granulosa cells in mature ovarian follicles. This study provides evidence that the ovulatory stimulus includes induction of the gene for regulator of G-protein signaling protein-2 (RGS2). Immature Wistar rats were primed with 10 IU eCG s.c., and 48 h later the 12-h ovulatory process was initiated by 10 IU hCG (a homolog of LH) s.c. Ovarian RNA was extracted at 0, 2, 4, 8, 12, and 24 h after injecting the animals with hCG. The RNA extracts were used for reverse transcription-polymerase chain reaction differential display to detect gene expression in the stimulated ovarian tissue. Two of the amplified cDNAs that were upregulated within 2 h after the ovaries had been stimulated by hCG were homologous to segments of the mouse gene for RGS2. In situ hybridization indicated that the RGS2 mRNA was expressed in the granulosa layer of mature follicles. In conclusion, the gene for RGS2, which is known to regulate membrane signaling pathways, is transcribed in ovarian follicles in response to an ovulatory dose of gonadotropin.

Animals↗
PubMed2000

Expression of tumor necrosis factor-stimulated gene-6 in the rat ovary in response to an ovulatory dose of gonadotropin.

Current evidence supports the hypothesis that the biochemical events of mammalian ovulation are analogous to an acute inflammatory reaction. This study reveals that tumor necrosis factor-stimulated gene-6 (TSG-6), which encodes a member of the superfamily of hyaluronan-binding proteins that is specifically translated in inflammatory reactions, is expressed in ovarian follicles that have been induced to ovulate. Immature Wistar rats were primed with 10 IU equine CG s.c.; and 48 h later, the 12-h ovulatory process was initiated by 10 IU human CG (hCG), s.c.. Ovarian RNA was extracted at 0, 2, 4, 8, 12, and 24 h after the primed animals were injected with hCG. The RNA extracts were used for RT-PCR differential display of amplified complementary DNAs (cDNAs) that represented gene expression in the stimulated ovarian tissue. Northern analysis of one of the differentially amplified cDNAs confirmed that it was part of a gene that was substantially up-regulated at 4-8 h after the ovaries had been stimulated by hCG. Subcloning and sequence analysis revealed that the cDNA matched the gene for TSG-6. In situ hybridization indicated that the TSG-6 messenger RNA was primarily located in the cumulus mass and the antral granulosa cells of large ovarian follicles. In conclusion, the data show that expression of TSG-6 is an integral part of the cascade of inflammatory-like changes that occur in an ovulatory follicle in response to a trophic hormone that couples with luteinizing hormone/hCG receptors.

Androstenols↗
PubMed2000

Induction of early growth response protein-1 gene expression in the rat ovary in response to an ovulatory dose of human chorionic gonadotropin.

Granulosa cells in a mature ovarian follicle have an abundance of LH/hCG receptors that respond rapidly to an ovulatory surge in gonadotropins. Within minutes, membrane signal transduction sets in motion metabolic changes that lead to follicular rupture. This study provides evidence that the initial ovarian response to such an ovulatory stimulus includes induction of the immediate-early transcription factor gene for early growth response protein-1 (Egr-1). Immature Wistar rats were primed with 10 IU equine CG (eCG), sc, and 48 h later the 12-h ovulatory process was initiated by 10 IU hCG, sc. Ovarian RNA was extracted at 0, 0.5, 1, 2, 4, 8, 12, and 24 h after the primed animals were injected with hCG. The RNA extracts were used for RT-PCR differential display for random detection of gene expression in the stimulated ovarian tissue. Northern analysis of one of the differentially amplified complementary DNAs confirmed that it was part of a gene that was significantly up-regulated within 1 h after the ovaries had been stimulated by hCG. Maximum transcription was at 4 h after hCG, and expression declined to 0 h control levels by 24 h after hCG. Subcloning and sequence analysis revealed that the complementary DNA matched the gene for Egr-1. In situ hybridization indicated that the Egr-1 messenger RNA was in the granulosa layer of mature follicles. Western blotting confirmed the temporal pattern of Egr-1 expression detected by differential display, Northern analysis and in situ hybridization. The Egr-1 protein is approximately 84 kDa. In conclusion, the data show that expression of the zinc finger transcription factor Egr-1 is an early event in the cascade of inflammatory-like changes that occur in an ovulatory follicle in response to a trophic hormone.

Androstenols↗
PubMed1999

Differentiation-dependent prolactin responsiveness and stat (signal transducers and activators of transcription) signaling in rat ovarian cells.

PRL activates an important cytokine signaling cascade that is obligatory for maintaining luteal cell function in the rat ovary. To determine when specific components of this cascade are expressed and can be activated by PRL, we analyzed the expression of receptor subtypes (short, PRL-R(s), and long, PRL-R(L)), the presence and kinetics of Stat (signal transducer and activator of transcription) activation using the PRL-response element (PRL-RE) of the alpha2M (alpha2-macroglobulin) gene, and the content and hormonal regulation of three specific modulators of cytokine signaling; the tyrosine phosphatases (SHP-1 and SHP-2), and the protein inhibitor of activated Stat3 (PIAS-3). These components were analyzed in differentiating granulosa/ luteal cells of hypophysectomized (H) rats and in corpora lutea of pregnant rats. Levels of PRL-R mRNAs increased as granulosa cells differentiated and reached maximal levels in luteal cells of pregnant rats where levels of PRL-R(s) approached those of PRL-R(L). The relative concentrations shifted from a 27-fold excess of PRL-R(L) in preovulatory granulosa cells to a 3.7-fold difference in luteal cells during midgestation. Despite the increased PRL-R(L) expression in differentiated granulosa cells, PRL did not stimulate detectable activation of Stats. Rather PRL activation of Stat5, principally Stat5b, occurred in association with luteinization. In contrast, granulosa cells of untreated immature and H rats contained a high level of DNA binding activity, which was shown to be comprised entirely of activated, phosphorylated Stat3. Treatment with estrogen and FSH reduced the amount of phosphorylated Stat3 and abolished its ability to bind DNA, an effect temporally related to increased PIAS-3. Expression of SHP-1 (but not SHP-2) was also hormonally regulated; SHP-1 mRNA and protein were high in granulosa cells of H rats, decreased by estrogen and FSH, and subsequently increased dramatically with luteinization. Of particular note, SHP-1 was localized in cytoplasm of granulosa cells in atretic follicles but was distinctly nuclear in luteal cells, indicative of different functional roles. Collectively, these results indicate that Stat3 and Stat5 are activated by distinct cytokine-signaling pathways modulated through differentiation-dependent transcriptional regulation of signaling pathway components and mediate distinct functional processes in the rat ovary: early follicle growth and atresia vs. luteinization.

Animals↗
PubMed1998

Molecular mechanisms of ovulation and luteinization.

Ovulation is a complex process initiated by the mid-cycle surge of luteinizing hormone (LH). Once initiated, a cascade of events occurs that culminates in the release of a fertilizable oocyte. The complex series of events involves specific ovarian cell types, diverse signaling pathways and temporally controlled expression of specific genes. This review will focus on several genes shown to control the ovulation process.

Animals↗
PubMed1996

Expression of triosephosphate isomerase transcripts in rat testis: evidence for retinol regulation and a novel germ cell transcript.

Vitamin A is essential for mammalian spermatogenesis. To isolate retinol-induced cDNAs from rat testis, vitamin A-deficient (VAD) rats were treated with retinol for 4 h and mRNA isolated from their testes was used to construct a subtractive cDNA library. One cDNA isolated from this library contained a sequence for triosephosphate isomerase (TPI). Northern blot analysis showed that the TPI cDNA hybridized with two transcripts in testis. A 1.4-kb transcript, which is the sole transcript found in most tissues, was expressed in the somatic cells of testis, whereas a novel 1.5-kb transcript was detected only in haploid spermatids. However, only the level of the shorter transcript increased with retinol treatment of the testis or of cultured Sertoli cells. Furthermore, screening of an adult rat testis cDNA library with the TPI cDNA yielded a cDNA putatively corresponding to the 1.5-kb transcript. Sequence analyses of the two TPI cDNAs revealed a 100-bp deletion in one cDNA that may be due to use of an alternative polyadenylation signal. These results suggest independent processing mechanisms for TPI expression in the somatic cells and the haploid germ cells of testis.

Aging↗
PubMed1996

Prolactin-induced activation and binding of stat proteins to the IL-6RE of the alpha 2-macroglobulin (alpha 2M) promoter: relation to the expression of alpha 2M in the rat ovary.

Cellular signaling events by which prolactin (PRL) might regulate gene expression were analyzed in rat ovarian tissues. Whole cell extracts (WCE) were prepared from ovaries of pregnant rats (Days 4, 7, 9-11, 15, 17, and 21) and of hormonally primed (estradiol and FSH) hypophysectomized (H) immature rats before, or 15 min to 24 h after, acute administration of PRL (10 micrograms, i.v.). The DNA binding activity in the WCE was analyzed by electrophoretic mobility shift assays using the alpha 2-macroglobulin (alpha 2M) promoter interleukin (IL)-6 response element (IL-6RE) known to confer PRL and IL-6 inducibility to transgenes in target cells, including cultures of luteinized granulosa cells. Injections of PRL stimulated the appearance of a specific binding activity in ovarian extracts of H rats and in corpora lutea and interstitial extracts of pregnant rats from Days 4-9 of pregnancy. The presence of this protein/DNA complex was transient. The greater amount of binding was observed in luteinized tissue and interstitial tissue compared to follicles; and the binding activity contained specific tyrosine phosphorylated Stat (signal transduction and activators of transcription) factors identified by specific antibodies as acute phase response factor (APRF or Stat 3) and mammary gland factor (MGF, or Stat 5 [a and b]). In contrast to the transient activation and appearance of these factors in response to acute PRL treatment as administered to H rats or to pulsatile PRL release as occurs in early pregnancy, elevated levels of the same activated Stat factors were observed in WCE of CL and interstitial tissue prepared at mid-gestation (Days 10-17) when endogenous release of rat placental lactogen (rPL) is chronically elevated in serum. During this period, administration of additional exogenous PRL did not stimulate further activation (binding) of the Stat factors. During luteal regression (Day 21 of gestation) no binding was observed in the absence of PRL, and the response to PRL was markedly diminished despite the constitutive presence of Stat proteins and the Janus kinase that phosphorylates and activates these factors. Elevated binding of these factors to the IL-6RE of the alpha 2M promoter was associated with the expression of alpha 2M mRNA in luteinized granulosa cells and corpora lutea, indicating that activation of Stat factors is one mechanism by which PRL/rPL transactivates the alpha 2M gene in the tissue.

Animals↗
PubMed1995

Immunization against the N-terminal peptide of the inhibin alpha 43-subunit (alpha N) disrupts tissue remodeling and the increase in matrix metalloproteinase-2 during ovulation.

Immunization of ewes against the N-terminal peptide of inhibin alpha 43 (alpha N) reduces fertility; this is thought to be due to impaired oocyte release at ovulation. This study further investigates the effect of alpha N immunoneutralization on the ovulatory process. Light microscopy was used to examine the effects of alpha N immunization of the tissue-remodeling process during ovulation and formation of the corpus luteum (CL) structure. Changes in follicular levels of matrix metalloproteinase-2 (MMP-2) with approaching ovulation were also investigated in normal and alpha N-immunized ewes. Differences in structure of 2-day-old CL were observed between control and alpha N-immunized ewes. Control CL had confluent luteal tissue throughout the internal structure and invaginations of theca and vasculature were common and penetrated deep into the luteal tissue. Immunized ewe CL had large fluid-filled antra, giving them a cystic appearance; luteal tissue remained a thin 10- to 15-cell layer lining the wall surrounding the antrum. Infolding of the surrounding tissue was incomplete, and thecal/vascular invaginations were rare and failed to penetrate into the luteal tissue. Morphologically normal rupture stigma were seen at the apex of both control and alpha N-immunized CL. Gelatin-digesting activity in follicular fluid collected 0, 12, and 24 h after hCG administration in control ewes increased significantly as the time of ovulation approached (827 +/- 182, 842 +/- 159, and 1230 +/- 89 mU/ml, respectively, in Exp 1; 743 +/- 32, 1182 +/- 98, and 1306 +/- 91 mU/ml at the same times in Exp 2). alpha N immunization reduced follicular gelatinase activity at each time in Exp 1 (533 +/- 132, 740 +/- 67, and 809 +/- 147 mU/ml) and Exp 2 (587 +/- 21, 768 +/- 27, and 891 +/- 53 mU/ml); the reduction was significant at 24 h in Exp 1 and at all times in Exp 2. Gelatin zymography of follicular fluid revealed bands of gelatinase of 72/67 kilodaltons, consistent with latent and active MMP-2. The area digested by both latent and active MMP-2 increased with approaching time of ovulation and was reduced by alpha N immunization. These data suggest that MMP-2 has a role in the tissue-remodeling processes of ovulation and CL formation in the ewe and that immunization against alpha N, which impairs fertility, effects the preovulatory cascade of intrafollicular proteolytic activity, reducing MMP-2 levels and disrupting normal CL formation.

Animals↗
PubMed1994

Effect of active immunization against the amino-terminal peptide (alpha N) of the alpha 43 kDa subunit of inhibin (alpha 43) on fertility of ewes.

Immunization against the amino-terminal peptide (alpha N) of the alpha 43 subunit of inhibin was shown previously to reduce fertility in ewes. The aim of this study was to examine the effects of active immunization of ewes against alpha N on egg recovery and fertilization rates. Ewes were immunized against alpha N immunogen, and were given 800 I.U. of pregnant mare's serum gonadotrophin at the end of treatment with intravaginal progesterone to synchronize the oestrous cycles. Control ewes received adjuvant only. The ewes were run with fertile rams, and 4 days after withdrawal of the progesterone device the oviducts were flushed to recover eggs and luteal structures on the ovaries were recorded. Eggs were recovered from 17/19 (90%) control ewes compared with 4/16 treated ewes (25%) (P < 0.01), and the egg recovery rates were 76% (45/59) and 17% (7/42) respectively (P < 0.001). The mean number of corpora lutea (CL) per ewe were similar (3.1 +/- 1.4 v. 2.6 +/- 1.0) but several CL in the treated ewes did not appear to have ruptured, and 2 treated ewes had cystic follicles and no CL. There were no apparent differences in either the fertilization rates or the stages of development of fertilized eggs between treated and control ewes. Antibody binding levels in follicular fluid were approximately half those found in peripheral plasma. It is concluded that immunization of ewes against alpha N leads to lowered fertility by suppressing ovulation, implicating alpha N in the normal ovulatory process.

Animals↗
PubMed1994

Pituitary and ovarian function in ewes immunized against the amino-terminal peptide (alpha N) of the inhibin alpha 43-subunit.

Immunization of ewes against the amino-terminal peptide (alpha N) of the pro-alpha-subunit of inhibin has been shown to reduce fertility, thought to be due to disruption of ovulation. The aims of this study were to examine the effects of active immunization of ewes against alpha N on circulating concentrations of FSH, LH and on ovarian inhibin and progesterone, and to relate these observations to number of corpora lutea and oocyte recovery rates. Ewes were immunized against one or both of two recombinant full length bovine-alpha N immunogens (FP1 and FP2). Three experiments were performed in which jugular venous plasma was sampled from control and immunized ewes: (1) hourly across the oestrous surge of gonadotrophins (Expt 1); (2) daily for one entire oestrous cycle, and in the subsequent cycle, oviducts were flushed to recover ovulated eggs (Expt 2); and (3) samples were taken at 10 min intervals during the follicular and luteal phases (Expt 3). Binding of 125I-labelled alpha N1-26 to serum was greater (P < 0.05) in immunized groups than in controls for all experiments. The number of eggs per corpus luteum recovered from the oviducts was lower (P < 0.05) in the alpha N-immunized groups (39%) than in controls (88%). There were more (P < 0.05) corpora lutea per ewe in FP2 immunized groups 4 (1.8 +/- 0.45) and 5 (1.75 +/- 0.5) than in the control group (1.13 +/- 0.13), but no increase in group 3 (FP1; 1.4 +/- 0.24).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Binding sites for interferons on ovine and human endometrial membranes.

In the ewe, the major product of the preimplantation blastocyst is ovine trophoblast protein-1 (oTP-1), which is now classified as an omega-interferon (IFN). Receptors for IFN are present on sheep endometrium and vary cyclically, presumably modified by the actions of ovarian steroids. This study examined whether or not IFN receptors were present on human endometrium at any stage during the menstrual cycle. In addition, the steroid dependence of ovine endometrial IFN receptors was determined. Specific binding of 125I-labelled IFN (125I-IFN) to ovine endometrial membranes was substantially higher than binding to membranes derived from bovine spleen, human placenta or pooled human endometrium (relative specific binding 100:33:36:20). Human endometrial membrane preparations from proliferative-phase tissue showed very little specific binding (mean 0.8 +/- 0.3%, n = 4) in contrast to luteal-phase endometrium (2.1 +/- 0.3%, n = 8). Treatment of ovariectomized ewes with oestradiol-17 beta (E) resulted in significantly increased binding (117 +/- 7%) of 125I-IFN to endometrial tissues compared with tissue from ovariectomized (OvX, 75 +/- 7%), progesterone (P)-treated (69 +/- 7%), or (E + P)-treated (81 +/- 8%) groups (P < 0.05); all were compared with binding to pooled ovine luteal-phase tissue, 100%. There were no differences between the other three groups. Scatchard analysis showed binding affinity of the same order for the sheep and human receptors (Kd = 10(-10) mol L-1) but binding capacity was considerably lower for human (6.0 fmol mg-1) than for sheep (47-123 fmol mg-1) endometrium.(ABSTRACT TRUNCATED AT 250 WORDS)

Amnion↗
PubMed1991

Peripheral concentrations of immunoreactive inhibin during pregnancy and parturition in the ewe.

The aim of this study was to measure the peripheral concentrations of immunoreactive inhibin (ir-inhibin) and progesterone (P) during pregnancy and parturition in the ewe and to relate the concentrations of ir-inhibin to P and to the number and sex of the fetuses. P increased across pregnancy with higher levels in ewes with 2 fetuses (n = 5) than in those with 1 fetus (n = 6), and concentrations falling before birth. ir-Inhibin concentrations were relatively stable during the first 40 days of pregnancy for example (Day 20, 34.7 +/- 2.9 pmol L-1; mean +/- s.e.m., n = 11). After Day 40, inhibin fell in all ewes to reach less than or equal to 2.5 pmol L-1 after Day 80 (mean on Day 103, 6.3 +/- 1.2 pmol L-1), and remained low until 2 days before parturition when concentrations rose sharply, peaking at or around the day of birth in all ewes (21.5 +/- 2.1 pmol L-1). Thereafter, ir-inhibin fell and remained low or undetectable for up to 10 days in the six ewes still being sampled. ir-Inhibin concentrations in ewes carrying one (n = 6), two (n = 5) or three fetuses (n = 1) did not differ at any stage of pregnancy examined. The sex of the fetus did not appear to influence the peripheral concentrations of ir-inhibin in the ewe.

Analysis of Variance↗
PubMed1989

Sindbis virus mutations which coordinately affect glycoprotein processing, penetration, and virulence in mice.

Rapid penetration of baby hamster kidney cells was used as a selective pressure for the isolation of pathogenesis mutants of the S.A.AR86 strain of Sindbis virus. Unlike most Sindbis virus strains, S.A.AR86 is virulent in adult as well as neonatal mice. Two classes of mutants were defined. One class was attenuated in adult mice inoculated intracerebrally as well as in neonatal mice inoculated either intracerebrally or subcutaneously. Sequence analysis of the glycoprotein genes of the parent virus and three such mutant strains revealed a single point mutation which resulted in an amino acid change at position 1 in the E2 glycoprotein. The change from a serine in S.A.AR86 to an asparagine in the mutants created a new site for N-linked glycosylation which appeared to be utilized. This mutation did not retard release of infectious particles; however, mutant virions contained the E2 precursor protein (PE2) rather than the E2 glycoprotein itself. The mutants also lost the ability to bind two E2-specific monoclonal antibodies, R6 and R13. A second class of mutants was attenuated in neonatal mice upon subcutaneous inoculation but remained virulent in adults and in neonates when inoculated intracerebrally. Sequence analysis of three such strains revealed the substitution of an arginine residue for a serine at position 114 in the E2 glycoprotein. Reactivity with monoclonal antibodies R6 and R13 was reduced, yet members of this mutant class were more susceptible than S.A.AR86 to neutralization by these antibodies.

Amino Acid Sequence↗