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S Robinson

Publications and source records attributed to S Robinson.

At least 145 records · Page 8Linked to original sources
PubMed1998

The chemokine growth-regulated oncogene-alpha promotes spinal cord oligodendrocyte precursor proliferation.

Chemokines, (chemotactic cytokines) are a family of regulatory molecules involved in modulating inflammatory responses. Here we demonstrate that the chemokine growth-regulated oncogene-alpha (GRO-alpha) is a potent promoter of oligodendrocyte precursor proliferation. The proliferative response of immature spinal cord oligodendrocyte precursors to their major mitogen, platelet derived growth factor (PDGF), is dramatically enhanced by GRO-alpha present in spinal cord conditioned medium. One source of GRO-alpha is a subset of spinal cord astrocytes. Cultures of astrocytes contain GRO-alpha mRNA and protein and secrete biologically active concentrations of GRO-alpha. In postnatal spinal cord white matter the location of GRO-alpha-immunoreactive cells is developmentally regulated: GRO-alpha+ cells first appear in ventral and later in dorsal spinal cord white matter. These results suggest that localized proliferation of oligodendrocytes is mediated by synergy between PDGF and GRO-alpha.

Animals↗
PubMed1998

Hormone-dependent regulation of GABAA receptor gamma subunit mRNAs in sexually dimorphic regions of the rat brain.

Transmission mediated by gamma-aminobutyric acid type A (GABAA) receptors expressed within the medial preoptic area (mPOA) and the ventromedial nucleus (VMN) of the hypothalamus is known to play critical, but contrasting, roles in regulating steroid-dependent sexual behaviours in rats. Previous studies have demonstrated a striking dichotomy in receptor composition between the two regions with regard to gamma, but not alpha or beta, subunit expression. To test if gonadal steroids regulate the expression of the gamma subunit genes within the mPOA and the VMN, in situ hybridization analysis for messenger RNAs encoding the gamma 1, gamma 2Short (gamma 2S) and gamma 2Long (gamma 2L) subunits was done in gonadectomized male and female rats and in gonadally intact females over the oestrous cycle. No significant differences in the expression of the gamma subunit mRNAs were observed in gonadectomized male versus female rats. Significant effects of gonadal state in female rats were observed for gamma 1 mRNA levels in the mPOA and gamma 2L levels in the VMN. These data demonstrate that gonadal hormones exert activational control of expression of GABAA receptor gamma subunit mRNAs and suggest that differences in receptor structure may contribute to the functional modulation of female sexual behaviours mediated by GABAergic transmission in these regions.

Animals↗
PubMed1998

Naamidine A is an antagonist of the epidermal growth factor receptor and an in vivo active antitumor agent.

The known 2-aminoimidazole alkaloid naamidine A (1) was isolated from a Fijian Leucetta sp. sponge as an inhibitor of the epidermal growth factor (EGF) receptor. The compound exhibited potent ability to inhibit the EGF signaling pathway and is more specific for the EGF-mediated mitogenic response than for the insulin-mediated mitogenic response. Evaluation in an A431 xenograft tumor model in athymic mice indicated that naamidine A exhibited at least 85% growth inhibition at the maximal tolerated dose of 25 mg/kg. Preliminary mechanism of action studies indicate that the alkaloid fails to inhibit the binding of EGF to the receptor and has no effect on the catalytic activity of purified c-src tyrosine kinase.

3T3 Cells↗
PubMed1998

Granulocyte colony-stimulating factor enhances bone marrow stem cell damage caused by repeated administration of cytotoxic agents.

Despite the increasing use of cytokines to circumvent the acute dose-limiting myelotoxicity of cancer treatment, little is known about the combined effects of cytotoxic agents and cytokines on the primitive stem cells responsible for long-term hematopoiesis. In an experimental model, we administered cytotoxic agents that have variable effects on primitive stem cells in C57BL/6 (B6)-mice. Mice received six every-other-week doses of cyclophosphamide (CY, 84 mg/kg), VP-16 (24 mg/kg) + cisplatinum (2.4 mg/kg), carboplatinum (50 mg/kg), chlorambucil (12 mg/kg), BCNU (13.2 mg/kg), or TBI (80 cGy). Granulocyte colony-stimulating factor (G-CSF; 250 microg/kg/day) was administered subcutaneously twice daily on days 3 to 6 after each dose of the cytotoxic agent. Comparison with animals receiving the cytotoxic agent alone was made to investigate the effects of G-CSF on long-term hematopoiesis. Hematopoiesis was measured 20 weeks after the last dose of the cytotoxic agent by assessment of peripheral blood counts, marrow cellularity, progenitor cell content (colony-forming units-spleen; CFU-S), and primitive stem cell number (long-term repopulating ability and day 28 and day 35 cobblestone area-forming cell [CAFC] frequencies). Exposure to cytotoxic agents alone resulted in a significant decrease in primitive stem cells (as measured by repopulating units [RU] and day 28 and day 35 CAFC content) in animals given carboplatinum, chlorambucil, BCNU, and TBI, but not in animals treated with cyclophosphamide or VP-16 and cisplatinum. The addition of G-CSF resulted in a significant decrease in stem cell content when compared with no G-CSF administration in animals treated with chlorambucil, BCNU, or TBI. Thus, G-CSF administered after repeated exposure to cytotoxic agents, appeared to damage the primitive stem cell compartment when used in combination with agents known to damage primitive stem cells. These results, although obtained in an experimental model, should raise concerns for the indiscriminate use of G-CSF in the clinic.

Animals↗
PubMed1998

Chemiluminescence determination of hydroperoxides following radiolysis and photolysis of free amino acids.

Hydroperoxides were determined in selected amino acids using three free radical generating systems by a sensitive (50 pmol limit of detection) and specific high performance liquid chromatography (HPLC)/chemiluminescence method. UVB and gamma radiation produced significant hydroperoxide formation, particularly in the aromatic amino acids tyrosine and tryptophan. Hydroperoxide yield was found to be dependent on both amino acid and irradiation source. Generation of hydrogen peroxide as a by-product of irradiation caused interference with chemiluminescence detection demonstrating the need for catalase addition. Hydroperoxides were not detectable following metal-catalysed H2O2 breakdown. We suggest that metal ions could interfere with the detection of hydroperoxides by causing preferential decomposition.

Amino Acids↗
PubMed1998

Inhibition of estrogen-induced sexual receptivity by androgens: role of the androgen receptor.

Both naturally occurring and synthetic androgens have been shown to inhibit estrogen-induced sexual receptivity when administered to ovariectomized (OVX) rats. The mechanisms by which androgens exert these effects, however, remain unclear. Experiments were conducted to determine the role of the androgen receptor in the inhibition of estrogen-induced sexual receptivity in OVX rats by using flutamide, an androgen receptor antagonist. In each experiment, OVX Long-Evans rats received 6 consecutive days of estradiol benzoate (EB; 2.0 microg/day) followed by 15 days of EB concurrent with flutamide (10. 0 mg/kg; twice daily) or the vehicle and one of the following androgens or the vehicle: dihydrotestosterone propionate (7.5 mg/kg), 3alpha-androstanediol (3.75 mg/kg), 17alpha-methyltestosterone (7.5 mg/kg), stanozolol (7.5 mg/kg), or nandrolone decanoate (7.5 mg/kg). On Day 15, all female rats received progesterone (P; 1.0 mg/rat) 4 h before testing. Tests for sexual receptivity were conducted on Days 3, 6, 14, and 15 of androgen/flutamide treatment. Each androgen inhibited sexual receptivity as expected, and concurrent treatment with flutamide reversed the inhibitory effects of all androgens on sexual receptivity on all test days. High levels of sexual receptivity were displayed in response to P on Day 15, regardless of experimental treatment. These results suggest that naturally occurring and synthetic androgens act at the androgen receptor to inhibit estrogen-induced sexual receptivity in OVX rats.

Androgen Antagonists↗
PubMed1998

Resource Intensity Weights and Canadian hospital costs: some preliminary data.

Different types of inpatients "consume" differing amounts of hospital resources, and it is important to be able to measure these differences in resource consumption. An equitable methodology for funding hospitals must take into account differences in case mix between facilities. An ability to examine these differences in case mix and resource utilization allows hospitals to focus efforts to improve efficiency. A standardized methodology for measuring resource consumption is critical to funding and resource allocation both at a global and organizational level. This study was undertaken to determine whether or not the Canadian system for measuring resource consumption, Canadian Institute for Health Information (CIHI) RIWs, was reflective of the relative cost differences between inpatient cases at the Greater Victoria Hospital Society (GVHS) and to identify RIWs with a significant difference in comparison to GVHS cost weights. A regression analysis was performed on the more than 30,000 inpatient cost profile records from the GVHS 1995-96 cost and patient activity data. The scope of the analysis was restricted to the 424 Case Mix Groups (CMGs) that had a minimum composition of five patient profiles. Comparisons of GVHS cost weights to CIHI RIWs yielded mostly positive results. With the noted exception of about 20 CMGs, there was a high correlation between the CIHI RIW and the GVHS actual cost weights. Hence, the GVHS cost weights can be viewed with confidence as representative of the relative cost differences between typical RIW value CMGs and actual costs.

British Columbia↗
PubMed1998

How much, and by what mechanisms, does growth hormone replacement improve the quality of life in GH-deficient adults?

The majority of studies (but not all) have demonstrated that adults with hypopituitarism of both childhood and adult onset have a diminished quality of life (QOL) in comparison with the normal population. Reductions in physical and mental energy, dissatisfaction with body image and poor memory have been reported most consistently. A specific role for growth hormone (GH) deficiency, as opposed to multiple pituitary hormone deficiency, has been observed for the memory deficit, which extends to both short- and long-term memory. Comparisons with normal siblings have confirmed the reduced QOL, although differences have been small. There is less consensus for a reduction in QOL when hypopituitary subjects are compared with patients with other chronic diseases, with studies supporting (in comparison with diabetics) and refuting (in comparison with patients following mastoid surgery) the reduction in QOL. GH replacement in adults has improved QOL, particularly in the domains of energy level and self-esteem, and memory has improved. The social impact of these changes may be considerable, with patients requiring fewer days' sick leave. A major placebo effect is present, however, and neutral results as well as positive have been reported in placebo-controlled trials. Where a positive effect has been observed, it has been more likely to occur in patients with a low QOL at the outset. It is otherwise impossible to predict at the outset those who will benefit from GH replacement. GH treatment has effects on body composition, exercise capacity, muscle strength, total body water and intermediary metabolism which would be expected to improve QOL. Replacement therapy also has side-effects, and it is the variable balance of the positive and negative effects, coupled with the difficulties of measuring QOL, which have led to the disparate results in the literature. There is probably also a true inter-individual variation, although the mechanisms of this are currently unknown.

Adult↗
PubMed1998

The health promoting nurse.

This paper suggests that (i) the dominance of an individualistic philosophy of nursing, (ii) nurses' own perceptions of their role and (iii) the hospital:community divide are all obstacles to health promotion being well integrated into nursing practice. It explores how these obstacles need to be overcome in order for the new health promoting nurse to emerge in practice. This is an attempt to clearly demonstrate 'who' the health promoting nurse is, 'what' she/he does, 'how' she/he works and 'where' she/he works.

Attitude of Health Personnel↗
PubMed1998

Getting started: choice and constraint in obtaining a post after qualifying as a registered mental nurse.

AIMS: To explore the extent to which obtaining a post after qualifying as a registered mental nurse (RMN) is a matter of exercising choice or experiencing constraints. BACKGROUND: The paper is drawn from the first phase of a longitudinal study of the careers of RMNs, commissioned in response to concerns about attrition from the mental health nursing workforce. METHODS: Questionnaires were sent to all RMNs (n = 550) qualifying from 3-year and post-registration courses in four regional health authorities; 80% (447) responded. FINDINGS: Some 73% had obtained a National Health Service (NHS) psychiatric nursing post shortly after qualifying; 95% had hoped to do so. Of those with a post, 71% had obtained their first choice of client group. A wide range of professional and personal constraints emerged as affecting job choice; lack of NHS posts in preferred location and/or speciality was cited most often. CONCLUSIONS: Support and guidance may be helpful for nurses experiencing delays in obtaining a post, or who are starting careers in a post which is not their first choice.

Attitude of Health Personnel↗
PubMed1998

Developing a career in the mental health services: guidance for student nurses.

Current concern about a shortage of nurses has led to attention focusing on the provision of career guidance as a strategy to facilitate retention in the workforce. This paper presents findings on career guidance provided for psychiatric nursing students, and thus adds to the very small volume of research that exists on guidance in nursing generally. Questionnaires were sent to 556 Registered Mental Nurses shortly after qualification; 80% responded. This represented the first phase of a longitudinal study of these nurses' careers. Participants were asked whether they had received information about career pathways that might be pursued, educational opportunities available and work experience outside the NHS. If not they were asked whether they had wanted such information. They were also asked whether they had been given advice about planning their own career. Only a minority of respondents had received information or advice, but the majority would have liked to have done so. The findings are discussed in the context of whether there is a need for career guidance and, if so, by whom it should be provided.

Adult↗
PubMed1998

The determinants of iron status in early pregnancy.

In pregnancy, the additional demands for Fe are thought to be met principally through increased maternal dietary Fe absorption and by mobilization of maternal Fe stores. In a general population sample of 576 women we examined the maternal and dietary characteristics which influenced Fe stores (assessed by serum ferritin concentration) in early pregnancy. The effects of these characteristics on two measures of functional Fe status (mean cell volume and haemoglobin concentration) were also considered. Serum ferritin concentrations were lower in multiparous women (P < 0.0001) and in those with a lower BMI (P = 0.01), and rose with increasing alcohol intake (P < 0.0001). Ferritin concentrations fell with increasing Ca intake (P < 0.0001); the proportion of women with serum ferritin values < or = 12 micrograms/l rose from 14% of the women in the lowest quarter of Ca intake to 29% of the women in the highest quarter. Mean cell volume and haemoglobin concentration were not related to Ca intake in early pregnancy. Although Ca added to test-meals reduces Fe absorption, long-term Ca supplementation has not been shown to lower plasma ferritin concentration, suggesting that high habitual Ca intakes would be unlikely to influence Fe status in non-pregnant individuals. Our findings show that in early pregnancy there is an association between high dietary Ca intake and lower Fe stores. This effect of Ca on one aspect of Fe status may result from its influence on Fe bioavailability.

Adult↗
PubMed1998

The role of selective cyclooxygenase isoforms in human intestinal smooth muscle cell stimulated prostanoid formation and proliferation.

Intestinal smooth muscle plays a major role in the repair of injured intestine and contributes to the prostanoid pool during intestinal inflammatory states. Cyclooxygenase (COX), which catalyzes the conversion of arachidonic acid to prostanoids exists in two isoforms, COX-1 and COX-2. The purpose of this study was to determine the relative contributions of COX-1 and COX-2 in the production of prostanoids by human intestinal smooth muscle (HISM) cells when stimulated by interleukin-1beta (IL-1beta) and lipopolysaccharide (LPS). Furthermore the effects of specific COX-1 and COX-2 inhibitors on the proliferation of smooth muscle cells was also evaluated. Confluent monolayer cultures of HISM cells were incubated with IL-1beta or LPS for 0-24h while control cells received medium alone. PGE2 and PGI2 as 6-keto-PGF1alpha and LTB4 were measured by a specific radioimmunoassay. COX enzymes were evaluated by Western immunoblotting. Unstimulated and stimulated cells were exposed to the specific COX-1 inhibitor valerylsalicylic acid (VSA) and the COX-2 inhibitors NS-398 and SC-58125. The effects of serum on proliferation were then evaluated in the presence of each of the specific COX inhibitors by incorporation of 3H-thymidine into DNA. IL-1beta and LPS increased both PGE2 and 6-keto-PGF1alpha in a dose dependent fashion with enhanced production detected two hours following exposure. Neither stimulus stimulated LTB4 release. Immunoblot analysis using isoform-specific antibodies showed that both COX-1 and COX-2 were present constitutively. Furthermore, COX-1 was upregulated by each inflammatory stimulus. In a separate set of experiments cells were pretreated with either the selective COX-1 inhibitor VSA or the selective COX-2 inhibitors NS-398 or SC-58125 prior to treatment with IL-1beta or LPS. The COX-1 and COX-2 inhibitors decreased both basal and IL-1beta and LPS stimulated prostanoid release. Spontaneous DNA synthesis was present and serum consistently increased proliferation. 3H-thymidine incorporation, stimulated by serum, was inhibited by both COX-1 and COX-2 inhibitors. This study suggests that the prostanoid response stimulated by proinflammatory agents of gut-derived smooth muscle cells appears to be mediated by both COX-1 and COX-2 enzymes. Proliferation of smooth muscles cells also appears to be influenced by both COX-1 and COX-2.

Blotting, Western↗
PubMed1998

Interaction between iron metabolism and 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice with variants of the Ahr gene: a hepatic oxidative mechanism.

The binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) with the aryl hydrocarbon (AH) receptor and subsequent changes in gene expression have been studied intensively, but the mechanisms by which these lead to toxicity are unclear. We investigated the influence of iron, previously implicated in TCDD-induced hepatic porphyria, in mice with alleles of Ahr that encode receptors with varied affinity for TCDD. The administration of iron to Ahrb-1 C57BL/6J (AH-responsive) mice before a single dose of TCDD (75 micrograms/kg) markedly potentiated not only the hepatic porphyria but also general hepatocellular damage and elevation of plasma hepatic enzymes. The formation of hydroxylated and peroxylated derivatives of uroporphyrins formed from uroporphyrinogen and the induction of a mu-glutathione transferase (GST) were consistent with the operation of an oxidative mechanism. In a comparison of C57BL/6J mice with Ahrb-2 BALB/c (AH-responsive) and Ahrd SWR and DBA/2 (AH-nonresponsive) mice, iron overcame the weak hepatic porphyria and toxicity responses in BALB/c and SWR strains but not in DBA/2. CYP1A isoforms are strongly implicated in the mechanism of porphyria, but activities were lowered by 20-30% with iron treatment, and a comparison of levels between strains did not fully account for the resistance of DBA/2 mice. Studies with the use of gel shift assays and cytosolic aconitase of the capacity of the iron regulatory protein controlling the translation of some iron metabolism proteins showed a significant difference between C57BL/6J and DBA/2 mice after the administration of TCDD. We conclude that iron potentiates both the hepatic porphyria and toxicity of TCDD in susceptible mice in an oxidative process with disturbance of iron regulatory protein capacity. Iron even overcomes the AH-nonresponsive Ahrd allele in the SWR strain but not in DBA/2 mice, which remain resistant.

Alleles↗