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Biomedical subjects

R K Moore

Publications and source records attributed to R K Moore.

At least 19 recordsLinked to original sources
PubMed2005

Health related quality of life of patients with refractory angina before and one year after enrolment onto a refractory angina program.

OBJECTIVE: This study was designed to assess the impact of a refractory angina programme on the health related quality of life for patients with chronic refractory angina (CRA) one year following enrolment. DESIGN: A one year prospective audit. SETTING: Specialist refractory angina clinic at a tertiary cardiac referral centre. PATIENTS: 69 consecutive refractory angina patients referred to a regional refractory angina centre from 1/03/2001 to 1/09/2002. INTERVENTIONS: Pain treatment algorithm in accordance with the recommendations of the national refractory angina guideline committee. MAIN OUTCOME MEASURES: Improvements in quality of life indices were assessed using Seattle angina questionnaire (SAQ), and short form-12 (SF-12) with changes in mood determined using the hospital anxiety and depression (HAD) questionnaire. RESULTS: All dimensions of the SF-12 and SAQ were superior at one year with significant improvement seen with the mental component of SF-12 (p = 0.023), and four of the five SAQ domains, angina stability (p = 0.028), angina frequency (p=0.02), treatment satisfaction (p=0.001) and quality of life (p < 0.001). All the significant changes within the SAQ domains were large enough to be considered clinically relevant. At one year the anxiety and depression domains were significantly improved from baseline (p = 0.015, 0.018) with clinical anxiety levels falling significantly from 55% to 40%, a relative reduction of 28% (p = 0.008). CONCLUSIONS: Implementation of the national refractory angina guidelines in a prospective study of 69 consecutive CRA patients significantly improved health related quality of life status at one year.

Aged↗
PubMed2003

The role of bone morphogenetic proteins in ovarian function.

Bone morphogenetic proteins (BMPs) represent the largest subclass of growth factors in the transforming growth factor beta (TGF-beta) superfamily. BMPs have proven to be multifunctional regulators of a wide variety of biological processes in numerous types of cell and tissue. The role of inhibins, activins and TGF-betas (which also belong to the TGF-beta superfamily) in reproduction has been studied extensively over the last 15 years. However, there were no reports on the role of BMPs in the mammalian ovary until 1999 when we reported an intrinsic ovarian BMP system replete with BMP ligands, receptors and novel biological functions. Since this report it has become clear that the BMP system plays an important role in the regulation of ovarian function, evidenced by the ability of BMPs to control granulosa cell proliferation and cytodifferentiation, as well as oocyte development. The physiological relevance of the BMP system has recently been highlighted by the discovery that genetic mutations in the BMP-15 ligand or the BMP type IB receptor lead to critical aberrations in folliculogenesis and ovulation. This review provides a current overview of the rapidly emerging field of the BMP system in mammalian ovarian function.

Animals↗
PubMed2001

Follistatin inhibits the function of the oocyte-derived factor BMP-15.

Recent studies have highlighted the importance of a novel oocyte-derived growth factor, bone morphogenetic protein-15 (BMP-15) in the regulation of proliferation and differentiation of granulosa cells in the ovary. Namely, BMP-15 stimulates granulosa cell mitosis and inhibits follicle-stimulating hormone (FSH) receptor mRNA expression in granulosa cell, thereby playing a critical role in the elaborate mechanism controlling ovarian folliculogenesis. At present, however, nothing is known about molecules which may regulate the biological activity of BMP-15. Here we demonstrate evidence that follistatin can form an inactive complex with BMP-15, through which follistatin inhibits BMP-15 bioactivities. The binding of follistatin to BMP-15 was directly demonstrated by a surface plasmon resonance biosensor, and the ability of follistatin to inhibit BMP-15 functions was determined by established BMP-15 bioassays using primary rat granulosa cells. Specifically, follistatin attenuated BMP-15 stimulation of granulosa cell proliferation and reversed BMP-15 inhibition of FSH receptor mRNA expression leading to the suppression of FSH-induced progesterone synthesis. This is the first demonstration of the biochemical interaction and biological antagonism of follistatin and BMP-15, which may be involved in the complex yet well-controlled mechanism of the regulation of follicle growth and development.

Activins↗
PubMed2001

Role of ERK1/2 in the differential synthesis of progesterone and estradiol by granulosa cells.

A major concept in mammalian ovarian physiology is that follicle-stimulating hormone (FSH) activates the granulosa cells (GCs) in the Graafian follicle to selectively produce estradiol, but not progesterone, during the follicular phase of the menstrual or estrous cycle. However, given the fact that FSH can induce production of both estradiol and progesterone by GCs cultured in vitro, it has been postulated for a long time that there is a factor present in the ovary that selectively prevents FSH-induced progesterone production. Here, we provide evidence that two members of the mitogen-activated protein kinase family, extracellular signal-regulated kinase-1 and -2 (ERK1/2) can differentially regulate FSH-stimulated estradiol and progesterone production. Using primary rat GCs from early antral follicles cultured in serum-free medium for 48 h, we found that the addition of a specific inhibitor of ERK1/2 activation, U0126, caused the attenuation or enhancement of FSH-induced progesterone or estradiol production, respectively, in a dose-dependent manner. Throughout the 48-h culture period in this culture system ERK1/2 molecules in their activated state (phospho-ERK1/2) were clearly detectable in GCs exposed to FSH. The addition of U0126 caused a decrease in the levels of phosphorylated but not unphosphorylated ERK1/2 which was maintained throughout the 48-h culture, suggesting that U0126 was continuously active to inhibit the phosphorylation of ERK1/2. The divergent regulation of FSH-induced progesterone and estradiol synthesis by U0126 was further supported by demonstrating that U0126 inhibits and stimulates FSH-induced mRNA levels of steroidogenic acute regulatory protein and P450 aromatase, respectively. Collectively, this study clearly identified ERK1/2 as the first intracellular signaling molecules that differentially regulate FSH-induced progesterone and estradiol synthesis in GCs.

Animals↗
PubMed2001

Biological function and cellular mechanism of bone morphogenetic protein-6 in the ovary.

The process of ovarian folliculogenesis is composed of proliferation and differentiation of the constitutive cells in developing follicles. Growth factors emitted by oocytes integrate and promote this process. Growth differentiation factor-9 (GDF-9), bone morphogenetic protein (BMP)-15, and BMP-6 are oocyte-derived members of the transforming growth factor-beta superfamily. In contrast to the recent studies on GDF-9 and BMP-15, nothing is known about the biological function of BMP-6 in the ovary. Here we show that, unlike BMP-15 and GDF-9, BMP-6 lacks mitogenic activity on rat granulosa cells (GCs) and produces a marked decrease in follicle-stimulating hormone (FSH)-induced progesterone (P(4)) but not estradiol (E(2)) production, demonstrating not only the first identification of GCs as BMP-6 targets in the ovary but also its selective modulation of FSH action in steroidogenesis. This BMP-6 activity resembles BMP-15 but differs from GDF-9 activities. BMP-6 also exhibited similar action to BMP-15 by attenuating the steady state mRNA levels of FSH-induced steroidogenic acute regulatory protein (StAR) and P450 side-chain cleavage enzyme (P450scc), without affecting P450 aromatase mRNA level, supporting its differential function on FSH-regulated P(4) and E(2) production. However, unlike BMP-15, BMP-6 inhibited forskolin- but not 8-bromo-cAMP-induced P(4) production and StAR and P450scc mRNA expression. BMP-6 also decreased FSH- and forskolin-stimulated cAMP production, suggesting that the underlying mechanism by which BMP-6 inhibits FSH action most likely involves the down-regulation of adenylate cyclase activity. This is clearly distinct from the mechanism of BMP-15 action, which causes the suppression of basal FSH receptor (FSH-R) expression, without affecting adenylate cyclase activity. As assumed, BMP-6 did not alter basal FSH-R mRNA levels, whereas it inhibited FSH- and forskolin- but not 8-bromo-cAMP-induced FSH-R mRNA accumulation. These studies provide the first insight into the biological function of BMP-6 in the ovary and demonstrate its unique mechanism of regulating FSH action.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2001

Gonadotropin-releasing hormone content in the brain and pituitary of male and female grass rockfish (Sebastes rastrelliger) in relation to seasonal changes in reproductive status.

The involvement of individual molecular forms of GnRH in the regulation of reproductive cyclicity in a viviparous marine teleost, the grass rockfish (Sebastes rastrelliger), was evaluated by relating the brain and pituitary content of the neuropeptide to reproductive status. The presence of sea bream (sb) GnRH, chicken GnRH-II, and salmon GnRH in the brain was confirmed by their elution pattern on HPLC and RIA. In addition, HPLC elution profiles suggest that there may be a fourth form of GnRH. All forms of GnRH were found in male and female brains in all reproductive conditions. However, only sbGnRH could be detected in appreciable amounts in the pituitary. Of the four forms of GnRH found in the rockfish, only sbGnRH fluctuated during the reproductive cycle and large accumulations were detected in the brains and pituitaries of postspawn females and regressed males. The accumulation of sbGnRH at the end of the reproductive cycle is suggested to reflect a decline in GnRH secretion relative to synthesis. The dominance of sbGnRH in the pituitary and its individual fluctuation in relation to seasonal changes in reproductive status suggests that sbGnRH is an important regulator of gonadotropin-mediated reproductive activity in rockfish.

Animals↗
PubMed2001

Effect of bone morphogenetic protein-7 on folliculogenesis and ovulation in the rat.

We have previously established the presence of a functional bone morphogenetic protein (BMP) system in the ovary by demonstrating the expression of BMP ligands and receptors as well as novel cellular functions. Specifically, BMP-4 and BMP-7 are expressed in theca cells, and their receptors by granulosa cells. These BMPs enhanced and attenuated the stimulatory action of FSH on estradiol and progesterone production, respectively. To investigate the underlying mechanism of the differential regulation, we analyzed mRNA levels for key regulators in the steroid biosynthetic pathways by RNase protection assay. BMP-7 enhanced P450 aromatase (P450(arom)) but suppressed steroidogenic acute regulatory protein (StAR) mRNAs induced by FSH, whereas mRNAs encoding further-downstream steroidogenic enzymes, including P450 side-chain cleavage enzyme and 3beta-hydroxysteroid dehydrogenase, were not significantly altered. These findings suggest that BMP-7 stimulation and inhibition of P450(arom) and StAR mRNA expression, respectively, may play a role in the mechanisms underlying the differential regulation of estradiol and progesterone production. To establish the physiological relevance of BMP functions, we investigated the in vivo effects of injections of recombinant BMP-7 into the ovarian bursa of rats. Ovaries treated with BMP-7 had decreased numbers of primordial follicles, yet had increased numbers of primary, preantral, and antral follicles, suggesting that BMP-7 may act to facilitate the transition of follicles from the primordial stage to the pool of primary, preantral, and antral follicles. In this regard, we have also found that BMP-7 caused an increase in DNA synthesis and proliferation of granulosa cells from small antral follicles in vitro. In contrast to the stimulatory activity, BMP-7 exhibited pronounced inhibitory effects on ovulation rate and serum progesterone levels. These findings establish important new biological activities of BMP-7 in the context of ovarian physiology, including folliculogenesis and ovulation.

Animals↗
PubMed2000

Circulating C-21 steroids in relation to reproductive condition of a viviparous marine teleost, Sebastes rastrelliger (grass rockfish).

Plasma concentrations of free, glucuronidated, and sulfated steroids were measured in grass rockfish (Sebastes rastrelliger) at identified stages of ovarian development and pregnancy using radioimmunoassays validated for the detection of individual steroids or compounds with a particular configuration. Changes in reproductive status were most clearly reflected in concentrations of free C-21 steroids. Previtellogenic, vitellogenic, and postspawn fish exhibited uniformly low concentrations of circulating C-21 steroids while pregnant fish showed a pronounced and significant increase in a series of free 17,20beta-dihydroxylated steroids together with 17,20alpha-P. Among individual steroids, the compound exhibiting the greatest fluctuation in relation to reproductive condition was 17,20beta-P-5beta, which during pregnancy showed a 22-fold increase from basal concentrations. Smaller relative increases in association with pregnancy were also seen in 17, 20beta-P, 17,20beta,21-P, and 17,20alpha-P (3.5-, 3.5-, and 5.5-fold increases, respectively). Fish in the final stages of pregnancy or which had recently spawned exhibited uniformly low concentrations of the C-21 steroids, indicating a drop in circulating amounts of these compounds around the time of parturition. The hormone profiles established during the annual reproductive cycle of the grass rockfish suggest that C-21 steroids may contribute to the endocrine mechanisms which regulate viviparity in this highly fecund marine teleost. The C-21 steroids characterized in this study may provide appropriate reference compounds in the future evaluation of this concept.

Aging↗
PubMed1990

Relationships between reproduction traits, age and body weight at calving, and days dry in first lactation Ayrshires and Holsteins.

Individual cow test day records collected between December 1979 and June 1986 were used to calculate measures of reproductive performance, age and weight at calving, and days dry for 7824 Ayrshire and 79,755 Holstein cows in first lactation. Separate analyses by breed were carried out according to a multiple-trait mixed model. Sixty-two Ayrshire and 369 Holstein sires were treated as random in the analyses. Ayrshires were, on average, older and lighter at calving than Holsteins, but the breeds differed little in reproduction measures and days dry. Heritabilities of fertility traits, days to first breeding, days open, and services per conception were all less than .015 in the multi-trait analyses. With the exception of body weight, heritability estimates for the other traits were less than .05. Phenotypic correlations between traits were almost identical for the two breeds, and genetic correlations tended to be similar. Exceptions involved the trait days to first breeding and services per conception, but heritabilities of these traits were close to zero (p less than .008) in Ayrshires. Fertility traits were positively correlated genetically. Genetic correlations between days open and both age and body weight at calving were small. The genetic correlation between age and weight at calving was -.90 and -.68 in Ayrshires and Holsteins, respectively. Genetic correlations between days dry and all traits except body weight were moderate and positive.

Aging↗
PubMed1987

A retinal smear technique for varying grating contrast.

We present here a technique for modulating contrast in gratings seen in Maxwellian-view or on a projection screen. The method can be used with achromatic or chromatic grating stimuli. It is based on a high frequency oscillatory displacement of the grating image, which in turn produces a smearing of the image on the observer's retina. The waveform of the displacement and its amplitude determine the appearance and contrast of the image produced on the retina.

Form Perception↗
PubMed1987

Blink-related eye movements.

Eye movements that accompany a blink have been measured in human subjects by the use of a visual-persistence method. With straight-ahead binocular viewing, each eye typically rotates nasalward and downward 1-2 deg during the closing phase of a blink. These eye movements are more rapid than the lid movements as recorded by high-speed photography. In fact, the eyes have already completed their initial rotation and started back again before the lids are fully closed. With off-center viewing, a blink causes each eye to rotate toward its primary position of regard. Indeed, if the eye is already in that position when the blink starts, the eye moves very little. With eyelids taped open, an eye tracker can be used, and records confirming the visual persistence tracings are obtained. Sequential photography of the cornea in profile reveals that the eye moves inward and back out again during a blink. The amplitude of this retraction is typically less than 1 mm; and its time course, slower than that of the rotational eye movements, parallels the closure and opening of the lids. In normal conditions of viewing there is no evidence of conjugate saccades, or of any large, upward rotation of the eyes (Bell's phenomenon) that was once believed to take place during a blink.

Blinking↗
PubMed1985

A method for determining threshold from single-unit neural activity.

A computationally straightforward method is described for determining the latency, duration and magnitude of stimulus-evoked single-unit neural activity. A unique feature of the method is its ability to define the neural response without reference to stimulus parameters. First, the temporal component of the spike train that represents the response is located and then that component is analyzed to determine the magnitude of the response. Intensity-response functions can then be constructed, using the number of extra spikes above baseline activity as a measure of response magnitude. Threshold can be defined as any point on the intensity-response function.

Action Potentials↗
PubMed1982

Changes in the human visually evoked cortical potential in response to chromatic modulation of a sinusoidal grating.

Human visually evoked cortical potentials (VECPs) were recorded from 4 subjects in response to the counterphase alternation of an equal brightness chromatic grating pattern. The pattern was constructed from 2 monochromatic sinusoidal gratings registered 180 deg out of phase. Eleven wavelengths from 450 to 650 nm (at 20 nm intervals) were used. Each wavelength was paired in the grating stimulus with every other to produce a total of 55 different chromatic gratings. The chromatic modulation depth (contrast) of each grating was varied and resulting VECPs were recorded. VECP amplitude was found to vary linearly with log chromatic modulation depth. VECP threshold values were inferred by extrapolation of linear regression lines to zero VECP amplitude. Chromatic modulation sensitivity functions were derived and a multidimensional scaling analysis of the data for each subject was performed. The data were adequately described by a two-dimensional geometric configuration of the 11 wavelengths used. The configurations were similar in shape to those obtained psychophysically by Butler and Riggs (1978) Vision Res. 18, 1407-1416, who used a similar stimulus pattern. Their shapes are consistent with an opponent-color model of color vision.

Adult↗
PubMed1982

Measurements of visual suppression during opening, closing and blinking of the eyes.

We have previously shown that the sensitivity of human vision, as measured with a stimulus that bypasses the eyelids, is briefly impaired at the time of an eyeblink. We now find that the visual loss is almost equally extensive during eye closure if the eyes then remained closed. But little impairment occurs during eye opening when the eyes then remain open. We have previously concluded that, in blinking, visual suppression is associated with an inhibitory signal sent out by the brain. We now conclude that this signal arises primarily as a corollary to the efferent discharge that closes the eyelids.

Adult↗
PubMed1982

Perception of suprathreshold stimuli during saccadic eye movements.

We have investigated the extent to which a graded series of suprathreshold stimuli are perceptually weakened by saccadic suppression. Stimuli were brief decrements of variable amplitude in the illumination of a Ganzfeld. For each of several decrements presented during fixation, we determined a matching amplitude of decrement presented during saccades. The measure of saccadic suppression was the ratio of these two amplitudes. The matches made by three observers exhibit ratios as high as 6:1 (0.8 log unit of suppression) near the threshold. Suppression decreases systematically as the strength of the stimulus increases, reaching 0.1 log unit or less for stimuli 2 log units above threshold.

Eye Movements↗
PubMed1982

Rapid ventilatory responses to changes in insufflated CO2 in awake roosters.

The ventilatory responses to pulses or steps in the fraction of CO2 in the insufflated gas stream (FICO2) in awake, unidirectionally ventilated White Leghorn roosters (Gallus domesticus) were studied. Within 0.2-0.5 s of the change in FICO2 at the syrinx, a change in inspiratory or expiratory flow occurred. Increases in FICO2 increased flow and tidal volume (VT), whereas decreases in FICO2 decreased flow and VT. Expiratory duration (TE) was markedly prolonged by decreases in FICO2 and shortened by increases. Inspiratory duration was affected little by FICO2 changes. The TE response to pulses of FICO2 (0.2-0.4 s duration) revealed a time dependency such that a maximum effect occurred when the pulses arrived at the syrinx at approximately midexpiration. The magnitudes of the responses were approximately proportional to the amplitude and duration of the FICO2 changes, but decreases in FICO2 had greater effects than increases. A likely receptor site for these responses is the intrapulmonary chemoreceptors, which appear to function in a reflex controlling airflow and timing of the ongoing breath.

Animals↗