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Biomedical subjects

S H Russell

Publications and source records attributed to S H Russell.

At least 19 recordsLinked to original sources
PubMed2002

Chronic intraparaventricular nuclear administration of orexin A in male rats does not alter thyroid axis or uncoupling protein-1 in brown adipose tissue.

Orexin A, synthesised in the posterolateral hypothalamus, has widespread distribution including the paraventricular nucleus (PVN), which is rich in thyrotropin-releasing hormone (TRH) neurones. Nerve fibres in the PVN synapse on neurones that send polysynaptic projections to brown adipose tissue (BAT), which is important in thermogenesis. A number of observations suggests orexin A may be involved in regulation of metabolism and thermogenesis. We investigated the effect of orexin A injected intracerebroventricularly (ICV) on thyroid-stimulating hormone (TSH) and thyroid hormones in male rats. We then examined the effect of chronic iPVN injections of orexin A on plasma TSH and uncoupling protein-1 (UCP-1) protein in BAT. Orexin A (3 nmol) administered ICV significantly suppressed plasma TSH at 10 and 90 min. Orexin A (0.3 nmol) administered into the PVN twice daily for 3 days significantly increased day-time 2-h food intake, but did not significantly alter nocturnal food intake. Though chronic iPVN orexin A altered diurnal food intake, there was no effect on 24-h food intake or body weight. Furthermore, orexin A administered chronically into the PVN did not alter UCP-1 level in BAT, or plasma hormones relative to saline injected animals. Chronic iPVN orexin A does not appear to influence thermogenesis through activation of UCP-1 or the thyroid axis.

Adipose Tissue, Brown↗
PubMed2002

Effects of melanocortin receptor ligands on thyrotropin-releasing hormone release: evidence for the differential roles of melanocortin 3 and 4 receptors.

The hypothalamic melanocortin system is important in the central regulation of food intake and body weight. We have previously demonstrated that intracerebroventricular administration of alpha-melanocyte stimulating hormone (alpha-MSH), a nonselective MC3 and MC4 receptor agonist, stimulated plasma thyroid-stimulating hormone, and agouti-related protein (AgRP), an MC3 and MC4 receptor antagonist, suppressed it. In this study, we investigated the effects of MC3 and MC4 receptor (MC3-R and MC4-R) selective agonists and antagonists on the release of thyrotropin-releasing hormone (TRH) from hypothalamic explants in vitro. alpha-MSH stimulated TRH release from the rat hypothalamic explants (alpha-MSH 100 nm 230 +/- 22.9% basal, P < 0.005). In contrast, gamma 2-MSH, a selective MC3-R agonist, suppressed TRH release (gamma 2-MSH 10 microns 76.2 +/- 7.4% basal, P < 0.05). AgRP (83-132), a nonselective MC3/4-R antagonist, induced no change in TRH release whilst JKC-363 (cyclic [Mpr11, D-Nal14, Cys18, Asp22-NH2]-beta-MSH 11-22), a selective MC4-R antagonist, suppressed it (JKC-363 10 nm 57.2 +/- 11.5% basal, P < 0.05). Both AgRP (83-132) and JKC-363 blocked alpha-MSH stimulated TRH release but only AgRP (83-132) blocked the inhibitory effect of gamma 2-MSH on TRH release. These data suggest differential roles for the MC3 and MC4 receptors in TRH release; MC3-R agonism inhibiting and MC4-R agonism stimulating TRH release.

Agouti-Related Protein↗
PubMed2001

The in vitro role of tumour necrosis factor-alpha and interleukin-6 in the hypothalamic-pituitary gonadal axis.

The adipocyte derived hormone leptin has been implicated as an important nutritional signal to the reproductive system, but the role of other adipocyte related cytokines is not clear. Tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6 are present in adipose tissue and released into the circulation where plasma levels correlate positively with body mass index and body fat mass. These cytokines could play a role in signalling nutritional status to the hypothalamic-pituitary-gonadal axis. We investigated the effects of TNF-alpha and IL-6 on basal and luteinizing hormone releasing hormone (LHRH) stimulated luteineizing hormone (LH) release from cultured anterior pituitary cells, harvested from either proestrus female or male Wistar rats. We examined the effects of TNF-alpha and IL-6 on LHRH release from hypothalamic explants harvested from proestrus female and male rats in vitro. IL-6 significantly suppressed LHRH stimulated LH release from male dispersed pituitaries throughout the dose range, but did not influence basal LH release. IL-6 had no effect on basal or LHRH stimulated LH release in dispersed pituitaries from proestrus females. By contrast, TNF-alpha significantly suppressed LHRH stimulated LH release in dispersed pituitaries from proestrus female rats in a dose responsive manner, but did not influence basal LH release. TNF-alpha had no effect on basal or LHRH stimulated LH release in dispersed pituitaries from male rats. TNF-alpha and IL-6 had no effect on LHRH release from male hypothalamic explants in vitro. TNF-alpha and IL-6 had no effect on LHRH release from proestrus female hypothalamic explants in vitro. TNF-alpha and IL-6 have differential effects in dispersed pituitaries harvested from males and proestrus female rats. TNF-alpha and IL-6 may be important in mediating some of the nutritional effects on the reproductive axis by acting at the level of the anterior pituitary rather than the hypothalamus.

Adipose Tissue↗
PubMed2001

The central effects of orexin-A in the hypothalamic-pituitary-adrenal axis in vivo and in vitro in male rats.

Orexin-A is synthesized in the posterolateral hypothalamus and immunoreactive fibres project to many central nervous system structures, including the paraventricular nucleus, which is rich in corticotropin releasing factor (CRF) neurones and neuropeptide Y (NPY) innervation. We investigated the central effects of orexin-A on the hypothalamic-pituitary-adrenal (HPA) axis by measuring plasma concentrations of corticosterone and adrenocorticotropic hormone (ACTH) in vivo. We explored the potential neuropeptide pathways involved by investigating the effects of orexin-A on CRF, NPY, arginine vasopressin (AVP) and noradrenaline release from hypothalamic explants in vitro. Intracerebroventricular (i.c.v.) injection of orexin-A (3 nmol) in male rats stimulated increases in plasma concentrations of corticosterone between 10 and 40 min after injection, and of plasma ACTH at 20 and 90 min after injection. Orexin-A significantly stimulated CRF and NPY release from hypothalamic explants in vitro. Orexin-A did not stimulate CRF release in the presence of the selective NPY Y1 receptor antagonist, BIBP3226. BIBP3226 alone did not alter CRF release from hypothalamic explants. Orexin-A had no effect in vitro on the release of other neuropeptides, AVP and noradrenaline, involved in the central regulation of the HPA axis. These results suggest that orexin-A is involved in activation of the HPA axis, and that these effects could be mediated via the release of NPY.

Adrenal Glands↗
PubMed2001

Orexin A interactions in the hypothalamo-pituitary gonadal axis.

The distribution of orexin A-immunoreactive neurons and orexin type I receptors in the CNS suggests important roles in regulating the hypothalamo-pituitary gonadal (HPG) axis and sexual behaviors. We examined orexin A interactions in the HPG axis in vivo and in vitro. Orexin A stimulated LH-releasing hormone (LHRH) release in hypothalamic explants harvested from male rats (+133%) and from females at proestrus (+233%), with no effect at estrus or metestrus. Orexin A dose dependently inhibited LHRH-stimulated LH release in dispersed pituitaries from proestrous females only. A selective NPY1-receptor antagonist abolished in vitro release of LHRH by orexin A. Hyperestrogenization in female rats reduced orexin A content in hypothalamus (-28%), midbrain (-26%), medulla (-40%), thalamus (-36%), olfactory tubercles (-25%), and cortex (-35%), brain regions that are important in HPG control and sex-cycle specific behaviors. Orexin A content was lower in hypothalamus (-20%) and higher in midbrain (+40%), medulla (+31%), and thalamus (+33%) at late proestrus vs. other cycle stages. Orexin A release after administration of 56 mM KCl was significantly greater in hypothalamic explants harvested on the morning of proestrus than at estrus or metestrus, and orexin A release was stimulated by estradiol (E2) in explants from males. These results reveal important interactions for orexin A in the HPG axis.

Animals↗
PubMed2000

Central administration of orexin A suppresses basal and domperidone stimulated plasma prolactin.

Orexin immunoreactive fibres are abundant in the hypothalamus suggesting a neuroendocrine regulatory role. Intracerebroventricular (ICV) administration of orexin A suppressed plasma prolactin in male rats by 71% at 20 min post-injection and 83% at 90 min post-injection (P < 0.005 vs saline at both time points). To investigate whether this effect was through the tuberoinfundibular dopaminergic (TIDA) system, a supra-maximal dose of domperidone, a dopamine receptor antagonist, was injected intraperitoneally (i.p.) prior to ICV injection of orexin A. ICV orexin A significantly suppressed domperidone (9 mg/kg)-stimulated plasma prolactin levels, by up to 40% (i.p. domperidone + ICV orexin A 3 nmol 34.5 +/- 7.4 ng/ml and i.p. domperidone + ICV orexin A 20 nmol 43.5 +/- 4.3 ng/ml, both P < 0.005 vs i.p. domperidone + ICV saline 57.9 +/- 2.7 ng/ml). Orexin A, 100 nM, significantly stimulated release of neurotensin, vasoactive intestinal polypeptide, somatostatin, corticotropin releasing factor and luteinizing hormone releasing hormone, but had no effect on release of dopamine, thyrotropin releasing hormone (TRH), vasopressin or melanin-concentrating hormone from hypothalamic explants in vitro. Orexin A did not alter basal or TRH stimulated prolactin release in dispersed pituitary cells harvested from male rats. The data suggest that ICV administration of orexin A suppresses plasma prolactin in part through a pathway independent of the dopaminergic system.

Animals↗
PubMed1998

A C-terminal fragment of Agouti-related protein increases feeding and antagonizes the effect of alpha-melanocyte stimulating hormone in vivo.

Agouti-related protein (Agrp) is present in rat and human hypothalamus and is structurally related to agouti protein. Overexpression of either of these proteins results in obesity. However the effect of exogenous Agrp and its in vivo interaction with alpha-melanocyte stimulating hormone (alphaMSH), the likely endogenous melanocortin 3 and 4 receptor (MC3-R and MC4-R) agonist, have not been demonstrated. We report that 1 nmol of Agrp(83-132), a C-terminal fragment of Agrp, when administered intracerebroventricularly (ICV) into rats, increased food intake over a 24-h period (23.0+/-1.4 g saline vs 32.9+/-2.3 g Agrp, p<0.05). The hyperphagia was similar to that seen when 1 nmol of the synthetic MC3-R and MC4-R antagonist SHU9119 was given i.c.v. (19.6+/-1.8 g saline vs 32.5+/-1.7 g SHU9119, p<0.001). Both Agrp(83-132) and SHU9119 blocked the reduction in 1-h food intake of i.c.v. alphaMSH at the beginning of the dark phase. This effect occurred independently of whether the antagonists were administered simultaneously, or nine hours prior, to the alphaMSH. We have also shown Agrp(83-132) is an antagonist at the MC3-R and MC4-R, with similar inhibition of cAMP activation to that previously reported for the full length peptide. In conclusion, Agrp(83-132) administered i.c.v. increases feeding with long lasting effects and is able to inhibit the action of alphaMSH. This interaction may be mediated by the MC3-R and/or MC4-R.

Agouti Signaling Protein↗
PubMed1996

Comparison of bladder, oesophageal and pulmonary artery temperatures in major abdominal surgery.

In this study we compared urinary bladder and oesophageal temperatures with the core temperature obtained from a pulmonary artery catheter in patients undergoing orthotopic liver transplantation. The bladder temperature was a closer approximation to pulmonary artery temperature in this group of patients than the oesophageal temperature and has much to recommend it in terms of convenience, safety and postoperative patient comfort.

Anesthesia, General↗
PubMed1995

Prevention of hypothermia during orthotopic liver transplantation: comparison of three different intraoperative warming methods.

Hypothermia is a frequent and sometimes clinically important problem during orthotopic liver transplantation. Numerous methods have been suggested to reduce intraoperative heat loss and promote active warming. In this study we compared an electric under mattress, a warm air under mattress and a forced warm air convective heating blanket. The forced air convective warming system was shown to produce significantly higher patient temperatures than the two other systems.

Adolescent↗
PubMed1994

Mivacurium in the myasthenic patient.

We have used mivacurium in four myasthenic patients presenting for thymectomy. Supramaximal single twitch stimulation was applied to the ulnar nerve at the wrist and the force of contraction of the adductor pollicis was measured. After an initial bolus dose of 30 micrograms kg-1 (approximately one-fifth of the normal intubating dose), we observed a mean 37.5 (SEM 5.6)% reduction in evoked twitch tension. Neuromuscular block was increased with incremental doses and maintained with repeat bolus doses of 15 micrograms kg-1 at 25% recovery. The interval between maintenance bolus doses remained constant (mean 5.9 (0.7) min). Spontaneous offset was rapid with a mean recovery index (T25-T75) of 11.9 (2.1) min. Provided anticholinesterase therapy is withheld in the immediate preoperative period, mivacurium would appear to be a safe and appropriate neuromuscular blocker in this variably sensitive group of patients. The cumulative dose required to establish full neuromuscular block varied between 60 and 90 micrograms kg-1. A maintenance infusion, commencing at 3 micrograms kg-1 min-1, is recommended, guided by neuromuscular monitoring.

Adult↗
PubMed1992

Directed excision of a transgene from the plant genome.

The effectiveness of loxP-Cre directed excision of a transgene was examined using phenotypic and molecular analyses. Two methods of combining the elements of this system, re-transformation and cross pollination, were found to produce different degrees of excision in the resulting plants. Two linked traits, beta-glucuronidase (GUS) and a gene encoding sulfonylurea-resistant acetolactate synthase (ALSr), were integrated into the genome of tobacco and Arabidopsis. The ALSr gene, bounded by loxP sites, was used as the selectable marker for transformation. The directed loss of the ALSr gene through Cre-mediated excision was demonstrated by the loss of resistance to sulfonylurea herbicides and by Southern blot analysis. The beta-glucuronidase gene remained active. The excision efficiency varied in F1 progeny of different lox and Cre parents and was correlated with the Cre parent. Many of the lox x Cre F1 progeny were chimeric and some F2 progeny retained resistance to sulfonylureas. Re-transformation of lox/ALS/lox/GUS tobacco plants with cre led to much higher efficiency of excision. Lines of tobacco transformants carrying the GUS gene but producing only sulfonylurea-sensitive progeny were obtained using both approaches for introducing cre. Similarly, Arabidopsis lines with GUS activity but no sulfonylurea resistance were generated using cross pollinations.

Acetolactate Synthase↗
PubMed1990

Contrasting patterns of neoplastic cell behaviour in long-term culture of bone marrow from patients with acute leukaemia and myelodysplastic disorders. A survey of responses in 31 cases with cytogenetic determination of neoplastic status of cultured cells in 17 studies.

Alterations in neoplastic cell behaviour responsible for increased production of terminally-differentiated granulocytes during long-term culture of bone marrow in different categories of acute leukaemia and myelodysplasia have been investigated. An increase in neutrophils associated with transition to a morphological picture identical to normal control cultures occurred in 15 of 25 studies on acute leukaemia in contrast to one of six studies on myelodysplastic disorders. An abnormal neoplastic karyotype was employed as a marker for monitoring the course of the neoplastic cell population in 11 studies in which there was progression towards a normal pattern of differentiation. An increase in differentiation was shown by this means to represent increased maturation of cells of the neoplastic process in one study on a myelodysplastic disorder, demonstrating domination of proliferative activity in culture by all of the myelodysplastic disorders examined. Transition towards normal differentiation in nine studies on acute leukaemia, however, correlated with partial or complete replacement of the acute leukaemic cells by normal haemopoietic series in de novo acute leukaemia, and by Ph positive cells in blast crisis of CML. Conversion to morphologically and cytogenetically normal cell populations in five studies on de novo acute leukaemia occurred in four cases which failed to respond to remission-induction therapy, suggesting the selective toxic effect capable of purging acute leukaemic cells from bone marrow operated by a mechanism which lacked cross-resistance to currently-employed cytotoxic agents.

Adult↗
PubMed1989

Abscisic acid-responsive sequences from the em gene of wheat.

We demonstrate that a chimeric gene containing the beta-glucuronidase (GUS) reporter gene linked to a 646-base pair 5' fragment (-554 to +92) from the abscisic acid (ABA)-regulated Em gene from wheat is correctly expressed in transgenic tobacco. We observe high activity only in embryos of mature seeds, and immature seeds cultured on ABA show enhanced expression. Using a rice transient assay, we identify a 260-base pair fragment (-168 to +92) that accounts for the ABA-specific 15-fold to 20-fold increase in GUS expression. A 50-base pair sequence (-152 to -103) fused 5' in either orientation to a truncated cauliflower mosaic virus promoter (35S) increases GUS activity threefold in the presence of ABA. Insertion of the Em 5'-untranslated region (+6 to +86) between the 35S promoter and the ATG of GUS results in a 10-fold increase in GUS activity in the absence of ABA. These results suggest the following two functional fragments of the Em 5' region: an ABA response element from -152 to -103 and an element between +6 and +86 that quantitatively increases the ABA response.

Abscisic Acid↗
PubMed1984

Determination of immunoglobulin class by pattern of absorption to protein A-sepharose coupled with immunoglobulin class specific antibodies.

The pattern of absorption of the different major immunoglobulin classes by protein A and protein A coupled with antibody to human IgA or IgM has been evaluated as a simple means of identifying the class of a particular immunoglobulin in small volumes of human serum. Rabbit anti-IgA or anti-IgM coupled with protein A-Sepharose gel effectively removed IgA or IgM respectively from human serum in addition to the subclasses of IgG removed by protein A alone. The manner in which an immunoglobulin-related property is removed from human serum by protein A and its conjugates with specific antibodies can thus serve as an index of the class of that particular immunoglobulin.

Absorption↗