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Biomedical subjects

A D Taylor

Publications and source records attributed to A D Taylor.

At least 37 records · Page 2Linked to original sources
PubMed1997

Electrophoretic separation of myosin heavy chain isoforms in the human m. vastus lateralis: references to reproducibility and relationships with force, electromechanical delay, fibre conduction velocity, endurance and electromyography.

The aim of this investigation was to determine the relationship between muscle performance and the myosin heavy chain (MHC) composition and the reliability of electrophoretically determined MHC compositions. A total of thirty-one male subjects participated in the experiments. Maximal voluntary isometric contractions (MVC) of the knee extensors were performed at an arbitrary knee angle of 90 degrees and the following variables were recorded: maximal isometric force, muscle fibre conduction velocity (MFCV), electromechanical delay (EMD), maximal rate of force development (MRFD), median frequency of EMG (MF) and iEMG. Static isometric contractions of the knee extensors were held at an angle of 90 degrees using contractile forces of 10%, 50% and 100% MVC, respectively. These tests were conducted on separate days. Muscle biopsy samples were obtained from the left m. vastus lateralis before MVC and static endurance tests. MHC protein isoform differences were determined through sodium dodecyl-polyacrylamide gel electrophoresis (SDS-PAGE) followed by densitometric analysis. Type I-MHC compositions of the m. vastus lateralis ranged from 20-68% with a mean of 49 +/- 18%, mean type IIa-MHC and type IIb-MHC percentages were 35 +/- 16% and 16 +/- 10%, respectively. MHC compositions of duplicate biopsy samples were not significantly different from that of original samples. The coefficients of variation calculated for duplicate biopsy samples suggested reasonable reproducibility for MHC isoform differentiation for type I-MHC and type-II MHC composition (CV = 12.6%). Differentiation between type IIa-MHC and type IIb-MHC was not always clear using the densitometric traces. Subjects with higher percentages of type II-MHC displayed significantly faster MFCV (r = 0.67, P < 0.1), isometric force development (r = 0.68, P < 0.1) and shorter periods of EMD (r = -0.72, P < 0.05). There was also a tendency toward faster MRFD in these subjects although results did not reach significance. Endurance times for isometric contractions held at 10%, 50% and 100% MVC to exhaustion were not correlated with MHC composition. No relationships between II-MHC composition and MF or iEMG were observed. It was suggested that surface electromyographic recordings obtained during isometric MVC did not reflect underlying differences in muscle fibre composition.

Adult↗
PubMed1997

Characterization and localization of lipocortin 1-binding sites on rat anterior pituitary cells by fluorescence-activated cell analysis/sorting and electron microscopy.

Lipocortin 1 (LC1) is an important mediator of glucocorticoid action in the anterior pituitary gland, where it appears to act via cell surface binding sites to suppress peptide release. We have exploited a combination of fluorescence-activated cell (FAC) analysis/sorting and electron microscopy to detect, characterize, and localize LC1-binding sites on the surface of dispersed rat anterior pituitary cells, using human recombinant LC1 (hu-r-LC1) as a probe. High affinity (Kd = 14 +/- 3 nM) hu-r-LC1-binding sites were detected on approximately 80% of anterior pituitary cells dispersed with collagenase. The binding characteristics of the ligand resembled those observed in leukocytes, in that it was saturable; concentration, Ca2+, and temperature dependent; and abolished by trypsin. Functional studies demonstrated an excellent correlation between the presence of the cell surface binding protein and the capacity of an anti-LC1 monoclonal antibody to abrogate the inhibitory actions of dexamethasone (10 nM) on the release of ACTH initiated in vitro by CRH-41 (1 nM). Morphological analysis of cells harvested by FAC sorting showed that 1) somatotrophs, corticotrophs, lactotrophs, thyrotrophs, and gonadotrophs were all included in the population expressing LC1 binding sites; and 2) the LC1-binding sites assume a punctate distribution across the cell surface. These data show that anterior pituitary cells express high affinity surface LC1-binding protein(s); they thus provide further evidence for a specific membrane mechanism of action of LC1 in regulating the endocrine function of the anterior pituitary.

Adrenocorticotropic Hormone↗
PubMed1997

An antisense oligodeoxynucleotide to lipocortin 1 reverses the inhibitory actions of dexamethasone on the release of adrenocorticotropin from rat pituitary tissue in vitro.

Our previous studies have demonstrated that lipocortin 1 (LC1, also called annexin 1) is an important mediator of glucocorticoid action in the neuroendocrine system, particularly with regard to the powerful inhibitory actions of the steroids on the secretion of ACTH and its hypothalamic releasing hormones. In the present study, we have used an antisense oligodeoxynucleotide (ODN) unique to LC1 to investigate further the role of this protein in the regulatory effects of dexamethasone on ACTH release in vitro from rat anterior pituitary cells. Pituitary cells dispersed with collagenase retained their functional and morphological integrity in vitro and sequestered ODNs in a time-dependent manner from the incubation medium. LC1 was readily detected in the cells by Western blot analysis or by immunoprecipitation/autoradiography after preloading with 35S-methionine/cysteine; the bulk of the protein was contained within an intracellular pool but a small amount was attached to the outer cell surface (pericellular). Dexamethasone (100 nm, 2.5 h) initiated de novo synthesis of LC1; it also increased the amount of LC1 in the pericellular pool detected by either method and caused a concomitant decrease in intracellular LC1. The responses to the steroid were prevented by the inclusion in the medium of an LC1 antisense ODN (50 nM, 3.5 h) but the corresponding sense and scrambled ODN sequences were inert. None of the ODN sequences tested influence the expression of annexin 5 in the pituitary tissue. CRH-41 (100 pM-1 mM), forskolin (1 nM-1 mM) and an L-Ca2+-channel opener BAY K8644 (100 pM-1 microM) initiated concentration dependent increases in immunoreactive- (ir-) ACTH release from the pituitary cells that were reduced (P < 0.01) by preincubation with dexamethasone (100 nM, 2.5 h). The inhibitory effects of the steroid were reversed by the LC1 antisense ODN (50 nM, P < 0.01), whereas the LC1 sense and scrambled control sequences (50 nM) were both ineffective in this respect (P > 0.05). The results add further support to the view that the acute inhibitory effects of glucocorticoids on the secretion of ACTH by the pituitary gland are dependent on the generation of lipocortin 1.

Adrenocorticotropic Hormone↗
PubMed1997

The relationship between electromyography and work intensity revisited: a brief review with references to lacticacidosis and hyperammonia.

The aim of this investigation was to re-evaluate the relationship between electromyography and work intensity during incremental work in light of highly discrepant literature. Trained male subjects participated in the study (n = 14). Each subject completed a VO2max test on a cycle ergometer. Tests started at a power output of 60 Watts with a 30 Watt.4 min-1 work increment. Each test was terminated at exhaustion. Blood was collected at the end of each work intensity for lactate and ammonia analysis. EMG were recorded from the vastus lateralis, rectus femoris and vastus medialis using pre-amplified surface electrodes. EMG were collected at each intensity over a period of 60 cycle revolutions. EMG signals were analyzed using integration and EMG spectral analysis. Gas exchange variables were recorded on-line for each test (15 second interval). Ammonia and lactate threshold points were surpassed at the same absolute work intensity (200 Watts) which was equivalent to 64-69% VO2max. When a linear model was applied to the iEMG data, coefficients of determination achieved were greater than those obtained when an exponential model was used for the vastus lateralis and medialis. Gradients of regression lines fitted to iEMG data at pre- and post-lactate/ammonia threshold work intensities were not different. Alternatively, the iEMG-work intensity relationship for the rectus femoris muscle tended to be curvilinear. Significant increases in iEMG were observed at post-lactate/ammonia threshold work intensities for the rectus femoris reflecting increases in fatigue and type II motor unit recruitment at these intensities. In general, median frequency of the EMG power spectrum function were unchanged during incremental work, although highly individualistic results were observed between some subjects and muscles. Grouped median frequency values were insensitive to changes in recruitment, metabolite accumulation and fatigue associated with the increases in work intensity. Consequently, the usefulness of EMG spectral analysis during incremental work was questioned.

Acidosis, Lactic↗
PubMed1996

Effect of acute normobaric hypoxia on quadriceps integrated electromyogram and blood metabolites during incremental exercise to exhaustion.

This investigation analysed the effects of environmental hypoxia (EU) on changes in quadriceps integrated electromyogram (iEMG) and metabolite accumulation during incremental cycle ergometry. Trained male subjects (n = 14) were required to complete two maximal oxygen uptake (VO(2max)) tests, one test during EH (F(1)0(2) = 0.135), the other during normoxia (F(1)0(2) = 0.2093). The EMG were recorded at each exercise intensity from the vastus lateralis, rectus femoris and vastus medialis muscles over 60 cycle revolutions. Mean integral values were then calculated. Blood was collected from the radial vein of consenting subjects (n = 8) at the end of each exercise intensity. Oxygen saturation of arterial blood (S(a)O(2)) was estimated using pulse oximetry. Gas exchange variables were collected on-line every 15 s. The results indicated that, without exception, EH significantly reduced total exercise time. Mean time to exhaustion in EH was 26.34 (SD 2.58) min compared with 35.25 (SD 4.21) min during N. The S(a)O(2) values indicated that severe arterial desaturation had been achieved by EH. Mean values for VO(2max) obtained in EH were 49 ml*kg* min(-1), compared with 59 ml*kg*min(-1) attained in N. Plasma lactate and ammonia concentrations were both significantly higher in EH. Increases in lactate and ammonia concentration were highly correlated in both N and EH. The onset of plasma lactate and ammonia accumulation occurred at the same exercise intensity in N. The iEMG responses of all three quadriceps muscles tended to be greater in the EH trials, although this difference was not significant. The basis for iEMG nonsignificance may have been related to large within sample variation in iEMG, sample size and the severity of the hypoxia induced.

Adult↗
PubMed1996

Molecular dynamics of the transition from L-selectin- to beta 2-integrin-dependent neutrophil adhesion under defined hydrodynamic shear.

Homotypic adhesion o2 neutrophils stimulated with chemoattractant is analogous to capture on vascular endothelium in that both processes depend on L-selectin and beta 2-integrin adhesion receptors. Under hydrodynamic shear, cell adhesion requires that receptors bind sufficient ligand over the duration of intercellular contact to withstand hydrodynamic stresses. Using cone-plate viscometry to apply a uniform linear shear field to suspensions of neutrophils, we conducted a detailed examination of the effect of shear rate and shear stress on the kinetics of cell aggregation. A collisional analysis based on Smoluchowski's flocculation theory was employed to fit the kinetics of aggregation with an adhesion efficiency. Adhesion efficiency increased with shear rate from approximately 20% at 100 s-1 to approximately 80% at 400 s-1. The increase in adhesion efficiency. Adhesion efficiency increased with shear rate from approximately 20% at 100 s-1 to approximately 80% at 400 s-1. The increase in adhesion efficiency with shear was dependent on L-selectin, and peak efficiency was maintained over a relatively narrow range of shear rates (400-800 s-1) and shear stresses (4-7 dyn/cm2). When L-selectin was blocked with antibody, beta 2-integrin (CD11a, b) supported adhesion at low shear rates (< 400 s-1). The binding kinetics of selectin and integrin appear to be optimized to function within discrete ranges of shear rate and stress, providing an intrinsic mechanism for the transition from neutrophil tethering to stable adhesion.

Antibodies, Monoclonal↗
PubMed1996

An on-demand system of delivering pre-mixed inspiratory gas for use during physical activity.

This study analysed the effectiveness of an on-demand system of supplying pre-mixed inspiratory gases to subjects under working conditions. A supply of pre-mixed inspiratory gas is often required in order to study the effects of acute hypoxia/hyperoxia on numerous physiological variables whilst normobaric pressure is maintained. The principle aim of this investigation was to determine if the introduction of the on-demand system resulted in any changes in minute ventilation (VE), oxygen consumption (VO2), respiratory rate (RR), tidal volume (VT) or endurance performance during incremental cycle ergometry to exhaustion. Trained male subjects participated in the study (n = 9). The subjects completed two incremental trials on a Monark cycle ergometer. The trials commenced at a power output of 60W implementing a 30 W.4 min-1 work increment. In one trial the subjects inspired ambient room air as per normal VO2max testing, whilst in the other trial the subjects inspired compressed air supplied from high pressure cylinders using a demand valve. Trial order was randomised. Raw data (time, heart rate, VI[ATPS], respiratory rate, tidal volume, FEO2 and FECO2) were recorded on line every 15 seconds. No differences in gas exchange variables were apparent at rest (VO2 VE RR, VT) nor during submaximal work between normal and on-demand trials. VO2max, VEmax and physical performance were also not significantly different between trials. On the basis of these findings, it was suggested that the on-demand system of supplying inspiratory gas resulted in minimal changes in gas exchange variables and performance during incremental work. Using this system of gas supply researchers can effectively supply subjects with premixed gas for little financial expense.

Adult↗
PubMed1995

L-selectin (CD62L) cross-linking signals neutrophil adhesive functions via the Mac-1 (CD11b/CD18) beta 2-integrin.

Emigration of leukocytes at sites of inflammation is initiated by the selectin family of carbohydrate-binding adhesion molecules. Molecular crossbridges initiate rolling of cells along the vascular endothelium where chemokines such as IL-8 and platelet activating factor (PAF) may be presented to their receptors on the leukocyte surface resulting in cell stimulation. Integrin activation appears to be a requirement for subsequent cell localization and diapedesis into the tissue. Several recent reports have demonstrated that ligation and cross-linking of neutrophil L-selectin results in neutrophil activation, including intracellular calcium release, superoxide production, and induction of mRNA for production of IL-8 and TNF-alpha. The purpose of this study was to examine whether ligation and cross-linking of L-selectin would specifically result in activation of beta 2-integrin-dependent adhesion. A fluorescence flow cytometric assay was developed that directly measures Mac-1-dependent cell adhesion. Fluorescent latex beads (2-microns diameter) were adsorbed with albumin or fibrinogen and added in excess to human neutrophils in a shear-stirred suspension. Following stimulation the kinetics of bead capture by neutrophils was continuously measured in real time on the flow cytometer. The onset of bead binding was detected in the presence of extremely low concentrations of PAF (10 pM) or formyl peptide (0.2 nM) stimulation. Ligation of L-selectin with whole IgG DREG200 or DREG56 Ab, but not controls (anti-CD44, -CD45, -CD11a), resulted in a significant potentiation of bead binding. Cross-linking F(ab')2 fragments of DREG200 with a goat anti-mouse F(ab')2 secondary Ab also stimulated beta 2-integrin-dependent adhesion in a dose-dependent fashion. A chimeric form of DREG200 expressing gamma 4 or gamma 1 isotypes of human Fc domain also stimulated cell adhesion when cross-linked. Surface expression of CD18 and an activation-dependent epitope, as detected with mAb24, also increased in response to L-selectin cross-linking. Cross-linking L-selectin induced significant adhesion and transmigration of neutrophils across human umbilical vein endothelial cells. We propose that cross-linking of L-selectin results in a cell signal that directly stimulates beta 2-integrin adhesive responses.

Adult↗
PubMed1995

Reproducibility and validity of the quadriceps muscle integrated electromyogram threshold during incremental cycle ergometry.

The principle aims of this research were, firstly, to determine if the relationship between integrated electromyography (iEMG) and exercise intensity was linear or threshold-like, and secondly, to determine if the relationship between iEMG and exercise intensity was repeatable on different test occasions. A group of 20 trained male subjects participated in the study. Each subject completed two incremental exercise tests on a Monark cycle ergometer. The tests were identical and separated from each other by a mean period of 42 (SD 12) h. The EMG signals were recorded from the vastus lateralis, rectus femoris and vastus medialis muscles at each intensity using surface electrodes. The relationship between iEMG and intensity was shown to be linear (r = 0.95 to r = 0.98) with no obvious iEMG thresholds present. The gradients of simple regression lines fitted to the iEMG compared to intensity were not significantly different on the retest occasion (CV 9%-12%). In summary, the findings of this study indicated that, during incremental exercise, the relationship between iEMG of the quadriceps musculature and exercise intensity was linear and not threshold-like. Furthermore, the linear relationship between iEMG and workload was repeatable on different test occasions.

Animals↗
PubMed1995

Palliation of malignant oesophageal perforation and proximal oesophageal malignant dysphagia with covered metal stents.

Twelve patients underwent placement of nine polyethylene-covered self-expanding metal stents (Cook), and three polyurethane-covered Wallstents (Schneider). All obstructing lesions were crossed fluoroscopically and stents placed under fluoroscopic control. Eleven of the 12 patients had recently undergone failed endoscopic stent insertion, which had resulted in oesophageal perforation. Technical success was achieved in 100% of patients, with no immediate complications. The stents were well tolerated and allowed the patients to eat within 12 h of their insertion. Covered stents are technically safe to insert, are best inserted fluoroscopically, and are particularly cost-effective in proximal oesophageal lesions and perforations, where Atkinson tubes are often not tolerated.

Adult↗
PubMed1995

Immunoneutralization of lipocortin 1 reverses the acute inhibitory effects of dexamethasone on the hypothalamo-pituitary-adrenocortical responses to cytokines in the rat in vitro and in vivo.

Our recent studies suggest that lipocortin 1 (LC1), a potential mediator of the anti-inflammatory, antiproliferative and anti-fever actions of glucocorticoids in peripheral tissues, may also contribute to the powerful negative feedback actions of the steroids on the hypothalamo-pituitary-adrenal (HPA) axis. In the present study we have used (1) an in vitro model to examine the influence of a specific neutralizing monoclonal anti-LC1 antibody (anti-LC1 mAb) on the capacity of dexamethasone to suppress the cytokine-induced release of the 41-amino acid corticotropin-releasing factor (CRF-41) and arginine vasopressin (AVP) from the rat hypothalamus and (2) a passive immunization protocol to assess the contribution of LC1 to the inhibitory actions of dexamethasone on the HPA responses to immunological (i.p. injection of interleukin 1 beta, IL-1 beta) and surgical (laparotomy under ether anaesthesia) stress. In vitro, Il-1 alpha (0.2 ng/ml), IL-1 beta (0.5 ng/ml), IL-6 (10 ng/ml) and IL-8 (1 ng/ml) each caused significant increases in the release of immunoreactive (ir)-CRF-41 and ir-AVP from hypothalami removed from rats adrenalectomized 10-12 days before autopsy; these responses were readily inhibited by preincubation of the tissue with dexamethasone (10(-7) M). The inhibitory actions of the steroid were attenuated and, in many instances, abolished by inclusion in the medium of a monoclonal anti-LC1 antibody (LC1 mAb, diluted 1:15,000); an isotype-matched control antibody (antispectrin alpha+beta, diluted 1:15,000) was ineffective in this regard. IL-1 alpha (0.2 ng/ml), IL-1 beta (0.5 ng/ml) and IL-6 (10 ng/ml) also initiated similar increases in the release of CRF-41 and AVP from hypothalami from intact rats which were effectively blocked by dexamethasone (10(-7) M). However, although the inhibitory actions of the steroid on the pharmacologically evoked release of CRF-41 were specifically overcome by anti-LC1 mAb (diluted 1:15,000), the steroid blockade of AVP release was not. In vivo, rats pretreated with either a polyclonal anti-LC1 antibody (anti-LC1 pAb, 1 ml/day s.c. for 2 days) or a corresponding volume of a nonimmune sheep serum (NSS) responded to immunological (IL-1 beta, 3 micrograms/kg i.p.) or surgical (laparotomy under ether anaesthesia) trauma with significant increases in the serum ACTH and corticosterone concentrations. In the NSS-treated groups, dexamethasone (100 micrograms/kg), which had no effect on the prestress concentrations of ACTH and corticosterone in the blood, completely prevented the HPA responses to both IL-1 beta and laparotomy.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenalectomy↗
PubMed1995

Dexamethasone suppresses the release of prolactin from the rat anterior pituitary gland by lipocortin 1 dependent and independent mechanisms.

Glucocorticoids have been shown repeatedly to inhibit the release of prolactin (PRL) in the rat but their site and mode of action is unknown. In the present study, we used an in vitro model to examine the requirement for protein synthesis for dexamethasone to suppress the release of immunoreactive (ir)-PRL release from the rat pituitary gland. In addition we have performed a series of in vitro and in vivo experiments to investigate the potential role in this regard of lipocortin 1 (LC1), a protein shown previously not only to mediate aspects of the anti-inflammatory and anti-proliferative actions of the glucocorticoids but also to contribute to the regulatory actions of the steroids in the brain-neuroendocrine system. In vitro, the release of ir-PRL from rat anterior pituitary tissue initiated by submaximal concentrations of VIP (10 nM). TRH (10 nM) or the adenyl cyclase activator forskolin (100 microM) was reduced significantly (p < 0.01) by preincubation (2 h) of the tissue with dexamethasone (0.1 microM). By contrast, ir-PRL release evoked by a submaximal concentration of the L-Ca2+ channel opener BAY K8644 (10 microM) was unaffected by the steroid although readily antagonised (p < 0.01) by nifedipine (1-100 microM). Exposure of the pituitary tissue to dexamethasone (0.1 microM) also caused a pronounced and highly significant increase in de novo protein synthesis, as assessed by the incorporation of 14C-lysine into the tissue (p < 0.001). This response was reduced markedly by the inclusion of the RNA and protein synthesis inhibitors, actinomycin-D (0.5 micrograms/ml) or cycloheximide (1.0 micrograms/ml), in the incubation medium (p < 0.001), both of which also effectively abrogated (p < 0.01) the dexamethasone-induced inhibition of the release of ir-PRL evoked by TRH. VIP and forskolin. Lipocortin I was readily detectable by Western blotting in protein extracts of freshly excised anterior pituitary tissue: a small proportion of the protein was found to be attached to the outer surface of the cells where it was retained by a Ca(2+)-dependent mechanism. Exposure of the tissue in vitro to dexamethasone (0.1 microM) or corticosterone (0.1 microM) but not 17 beta-oestradiol (0.1 microM) caused a pronounced increase in the amount of LC1 attached to the outer surface of the cells and concomitant decrease in the LC1 content of the intracellular LC1 pool. Addition of an N-terminal LC1 fragment. LC11-188 (10 pg-10 ng/ml), to the incubation medium reduced significantly (p < 0.01) the increases in ir-PRL release induced in vitro by VIP (10 nM) and forskolin (100 microM). By contrast, at all concentrations tested. LC11-188 (10 pg-10 ng/ml) failed to influence (p < 0.05) the highly significant (p < 0.01) ir-PRL response to TRH (10 nM). Similarly, the inhibitory actions of dexamethasone (0.1 microM) on the release of ir-PRL induced by VIP (10 nM) or forskolin (100 microM) but not by TRH (10 nM) were substantially reversed (p < 0.01) by a specific monoclonal anti-LC1 antibody while an isotype-matched control antibody was without effect. In vivo, rats pretreated with either a polyclonal anti LC1 antiserum (anti-LC1 pAb, 1 ml/day s.c. for 2 days) or a corresponding volume of non-immune sheep serum (NSS) responded to stress (laparotomy under ether anaesthesia) with significant (p < 0.05) increases in the serum ir-PRL concentration. In the NSS-treated group, the ir-PRL response to stress was effectively inhibited by dexamethasone (100 micrograms/kg i.p.) which had no effect on the pre-stress serum ir-PRL concentration. By contrast, in rats pretreated with anti-LC1 pAb dexamethasone failed to block the stress-induced release of ir-PRL. The results show clearly that the inhibitory actions of dexamethasone on PRL release are dependent on de novo protein synthesis and provide novel evidence for the involvement of both LC1-dependent and LC1-independent mechanisms.

Animals↗
PubMed1995

Dexamethasone inhibits the release of TSH from the rat anterior pituitary gland in vitro by mechanisms dependent on de novo protein synthesis and lipocortin 1.

Glucocorticoids have been shown repeatedly to inhibit the secretion of TSH in experimental animals and in man but their site and mode of action are unknown. In the present study, we have used an in vitro model to examine the effects of dexamethasone on the resting and pharmacologically evoked secretion of TSH by the rat anterior pituitary gland, and to show how they are influenced by inhibitors of RNA/protein synthesis. In addition, we have investigated the potential role of lipocortin 1 (LC1), a protein shown previously to contribute to glucocorticoid action in several systems, as a mediator of the glucocorticoid-induced suppression of TSH release in our in vitro preparation. The significant (P < 0.01) increases in the release of immunoreactive (ir)TSH from rat anterior pituitary tissue initiated by submaximal concentrations of TRH (10 nmol/l), vasoactive intestinal polypeptide (VIP, 10 nmol/l) or the adenyl cyclase activator, forskolin (100 mumol/l) were reduced significantly (P < 0.05) by preincubation of the tissue with dexamethasone (0.1 mumol/l). In contrast, irTSH secretion evoked by a submaximal concentration of the L-Ca2+ channel opener BAY K8644 (10 mumol/l) was unaffected by the steroid, although readily antagonised (P < 0.01) by nifedipine (1-100 mumol/l). Inclusion of actinomycin D (1.78 mumol/l) or cycloheximide (0.8 mumol/l), inhibitors of RNA and protein synthesis respectively, in the medium effectively abrogated the inhibitory effects of dexamethasone (0.1 mumol/l) on the secretory responses to TRH (10 nmol/l), VIP (10 nmol/l) and forskolin (100 mumol/l). LC1 was readily detectable by Western blotting in protein extracts of freshly excised anterior pituitary tissue. A small proportion of the protein was found to be attached to the outer surface of the cells where it was retained by a Ca(2+)-dependent mechanism. Exposure of the tissue to dexamethasone (0.1 mumol/l) caused a pronounced increase in the amount of cellular LC1 attached to the outer surface of the cells and a concomitant decrease in the intracellular LC1 pool. Progesterone (0.1 mumol/l) and aldosterone (0.1 mumol/l) were also weakly active in this regard, but thyroxine and tri-iodothyronine (0.1 mumol/l) were not. Addition of an N-terminal LC1 fragment, LC1(1-188) (0.05-0.53 pmol/l) to the incubation medium reduced significantly (P < 0.01) the increases in irTSH release induced by TRH (10 nmol/l), VIP (10 nmol/l) and forskolin (100 mumol/l), but failed to influence (P < 0.05) those initiated by BAY K8644 (10 mumol/l). Furthermore, the inhibitory actions of dexamethasone (0.1 mumol/l) on the release of irTSH provoked by TRH (10 nmol/l), VIP (10 nmol/l) and forskolin (100 mumol/l) were substantially reversed (P < 0.01) by a specific monoclonal anti-LC1 antibody, while an isotype-matched control antibody was without effect. The results show clearly that dexamethasone, a semi-synthetic glucocorticoid, acts at the pituitary level to inhibit the neurochemically evoked release of irTSH. They also provide novel evidence that the inhibitory actions of the steroid are dependent upon de novo RNA/protein synthesis and that they involve an LC1 dependent mechanism.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1995

Renal artery stenosis managed by Palmaz stent insertion: technical and clinical outcome.

OBJECTIVE: To assess the technical and clinical outcome of Palmaz renal artery stent insertion in patients with renal artery stenosis. DESIGN: Twenty-nine patients with radiological evidence of renal artery stenosis and hypertension (16 patients, mean +/- SD diastolic blood pressure 100.5 +/- 8.16 mmHg) and/or renal impairment (17 patients, mean +/- SD serum creatinine 376 +/- 169 mu mol/l) were referred for radiological intervention. Of these, 22 had ostial atheromatous lesions, six had atheromatous non-ostial lesions and one patient had fibromuscular dysplasia. Palmaz stent insertion was performed where either previous or concomitant percutaneous transluminal renal angioplasty (PTRA) had been unsuccessful. Technical success was defined primarily as <30% residual stenosis. A prospective radiological and clinical follow-up was performed and the results compared with the outcome following PTRA alone in a similar group of patients from our centre. RESULTS: Immediate technical success was achieved in all 29 patients. Follow-up angiography in 24 patients after a mean of 7 months showed restenosis in four patients. The hypertension was not 'cured' in any patient; a blood pressure fall was observed in seven patients (44%) and no change in the remaining nine subjects (56%). Renal function improved in four patients (24%), two of whom had angiotensin converting enzyme inhibitor-exacerbated renal impairment. This compares with an immediate technical success of 81% for PTRA alone, with cure in 50% and improvement in 32% of patients with hypertension and improvement in renal function in 64.7% of patients with renal impairment. CONCLUSIONS: Palmaz renal artery stent insertion has a higher technical success rate than PTRA, but the clinical improvement is disappointing in our patient population.

Adult↗
PubMed1994

Electromyographic correlates of the transition from aerobic to anaerobic metabolism in treadmill running.

This study analysed the changes in electromyographic (EMG) activity of the vastus lateralis, biceps femoris and gastrocnemius muscles during incremental treadmill running. The changes in EMG were related to the lactate and ventilatory thresholds. Ten trained subjects participated in the study. Minute ventilation, oxygen consumption, carbon dioxide expired and the fraction of oxygen in the expired gas were recorded continuously. Venous blood samples were collected at each exercise intensity and analysed for lactate concentration. The EMG were recorded at the end of each exercise intensity using surface electrodes. The EMG were quantified through integration (iEMG) and by calculating the mean power frequency (MPF). The iEMG measurements were characterized by a breakpoint in the vastus lateralis and/or gastrocnemius muscles in eight of the subjects tested. However, the results indicated that blood lactate concentrations had already begun to increase in a nonlinear fashion before the iEMG breakpoint had been surpassed. Consequently, the occurence of the lactate threshold cannot be attributed solely to the change in motor unit recruitment or rate coding patterns demonstrated by the iEMG breakpoint. The ventilatory threshold was shown to be a far more reliable and convenient noninvasive predictor of the lactate threshold in comparison with EMG techniques. In conclusion, the EMG measurements used in this study (i.e. iEMG and MPF) were not considered to be viable noninvasive determinants of the aerobic-anaerobic transition phase in treadmill running.

Adult↗