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R Smith

Publications and source records attributed to R Smith.

At least 37 records · Page 2Linked to original sources
PubMed2005

Inflammatory mediator release in normal bronchial smooth muscle cells is altered by pregnant maternal and fetal plasma independent of asthma.

Studies have shown that pregnancy can alter the pathophysiology of a pre-existing maternal disease such as asthma. However, the mechanisms that alter maternal asthma during pregnancy are presently unknown. Previous work has demonstrated that human bronchial smooth muscle (BSM) cells produce inflammatory factors in response to nonpregnant, atopic plasma. The aim of this study was to determine whether circulating pregnancy-derived factors in maternal and fetal plasma can stimulate inflammatory mediator release in BSM cells in the presence and absence of maternal asthma. Cultured human BSM cells were exposed to maternal and fetal plasma from normal pregnancies and pregnancies complicated by asthma. Inflammatory mediator release was determined by enzyme-linked immunosorbent assay (ELISA). Both maternal and fetal plasma from asthmatic and nonasthmatic individuals significantly increased production of interleukin (IL)-6 (ANOVA, P<0.001), regulated upon activation, normal T-cell expressed and secreted (RANTES) (ANOVA, P<0.01), and soluble intercellular cell-adhesion molecule-1 (sICAM-1) (ANOVA, P<0.01). There was no difference in inflammatory mediator release in response to asthma and nonasthmatic plasma. Eotaxin release was increased by pregnant asthmatic plasma (ANOVA, P<0.05). The results of this study suggest that circulating pregnancy-related factors can activate asthma-associated mediators in BSM cells. This change in BSM function may be one mechanism that contributes to increased asthma severity during pregnancy.

Asthma↗
PubMed2005

Synaptic dysfunction in Huntington's disease: a new perspective.

Huntington's disease (HD) is caused by a polyglutamine expansion in the protein huntingtin and is characterized by intraneuronal inclusions and widespread neuronal death at the late stage of the disease. In research, most of the emphasis has been on understanding the cell death and its mechanisms. Until recently, it was believed that the vast majority, if not all, of the symptoms in HD are a direct consequence of neurodegeneration. However, increasing evidence shows that subtle alterations in synaptic function could underlie the early symptoms. It is of particular interest to understand the nature of this neuronal dysfunction. Normal huntingtin interacts with various cytoskeletal and synaptic vesicle proteins that are essential for exocytosis and endocytosis. Altered interactions of mutant huntingtin with its associated partners could contribute to abnormal synaptic transmission in HD. This review describes recent advances in understanding synaptic dysfunction in HD.

Animals↗
PubMed2005

Case report: cystitis glandularis mimics bladder tumour: a case report and diagnostic characteristics.

We report a rare case of a 26-year-old patient presented with 3-week history of frank haematuria and suprapubic discomfort. Investigations revealed a tumour arising from the bladder wall and histology demonstrated cystitis glandularis. The literature review highlights the rarity of cystitis glandularis presented in such manner. Our radiographic and endoscopic images can also assist future diagnosis of the condition especially in patients in such age groups.

Adult↗
PubMed2005

Dietary n-3 polyunsaturated fatty acids suppress splenic CD4(+) T cell function in interleukin (IL)-10(-/-) mice.

Our laboratory has demonstrated that down-regulation of proliferation and cytokine synthesis by CD4(+) T cells in mice fed diets rich in n-3 polyunsaturated fatty acids (PUFA) is highly dependent on the involvement of the co-stimulatory molecule, CD28. It has been reported that the inhibitory cytokine interleukin (IL)-10 acts directly on T cells which up-regulate IL-10 receptor (IL-10R) expression following stimulation via CD28 by efficiently blocking proliferation and cytokine production. Thus, it was hypothesized that dietary n-3 PUFA would suppress T cell function through the effects of IL-10. The proliferation of purified splenic CD4(+) T cells activated in vitro with anti-CD3 and anti-CD28 (alphaCD3/CD28) from conventional mice (C57BL/6) fed either a control corn oil (CO)-enriched diet devoid of n-3 PUFA, docosahexaenoic acid (DHA; 22 : 6) or eicosapentaenoic acid (EPA; 20 : 5) for 14 days was suppressed by dietary DHA and EPA. Surprisingly, a similar trend was seen in IL-10 gene knock-out (IL-10(-/-)) mice fed dietary n-3 PUFA. IL-10R cell surface expression was also significantly down-regulated on CD4(+) T cells from both the C57BL/6 and IL-10(-/-) mice fed dietary n-3 PUFA after 72 h of in vitro stimulation with alphaCD3/CD28. Enzyme-linked immunosorbent assay (ELISA) measurements revealed that C57BL/6 mice fed DHA had significantly reduced interferon (IFN)-gamma and IL-10 levels 48 h post-activation. However, CD4(+) T cells from IL-10(-/-) mice fed dietary n-3 PUFA produced significantly greater levels of IFN-gamma than the CO-fed group. Our data suggest that in the absence of IL-10, CD4(+) T cells from n-3 PUFA-fed mice may up-regulate IFN-gamma. Suppressed CD4(+) T cells from n-3 PUFA-fed C57BL/6 mice may use mechanisms other than IL-10 to down-regulate T cell function.

Animals↗
PubMed2005

Hypermobility and sports injuries in junior netball players.

OBJECTIVE: To evaluate the incidence of hypermobility in young female netball players and to determine the relation between hypermobility, previous injuries sustained in netball or other sports, and the use of protective equipment. METHODS: Under 16 year old female netball players from a local suburban netball association were assessed for joint hypermobility using the validated Beighton score (0-9, with higher scores indicating increasing hypermobility). Player profiles and details of sporting injuries, both netball and non-netball, and the use of protective equipment were gathered by means of a self completed questionnaire. Parental and child consent was obtained. RESULTS: Two hundred netball players were recruited for the study. Twenty one percent of the subjects with a Beighton hypermobility score of 0-2 had sustained previous netball injuries compared with 37% with Beighton scores of 3-4, and 43% with scores of 5-9. These differences were significant (p<0.025). Injuries were most common in the ankle (42%), knee (27%), and fingers (15%). Thirty nine players (19%) wore protective equipment, and within this group 30 (77%) had sustained previous injuries. No association was detected between hypermobile joints and non-netball sporting injuries. CONCLUSIONS: In this study hypermobility was significantly associated with an increased prevalence of injuries in junior netball players. A targeted interventional approach may help to reduce injuries in this susceptible group.

Adolescent↗
PubMed2005

An audit of clinical practice in the management of head injured patients following the introduction of the Scottish Intercollegiate Guidelines Network (SIGN) recommendations.

A prospective study was conducted by the Scottish Trauma Audit Group (STAG) in A&E of Edinburgh Royal Infirmary to examine clinical practices in the management of head injured patients pre- and post-inception of the SIGN guidelines published in August 2000.1607 patients attended the department in two separate one month periods at equal intervals pre- and post-guidelines publication. The majority of patients with a SIGN indication for admission were admitted (93% pre- and 92% post-guidelines). For skull x ray (SXR) requests, in the pre-guidelines group, 92% of admitted patients with a SIGN indication for x ray had a SXR: this figure dropped to 79% post-guidelines. 36% of patients with a SIGN indication for CT actually had a scan pre-guidelines: this figure increased to 64% post-guidelines.57% of patients pre-guidelines and 44% of patients post-guidelines were discharged from A&E in accordance with the SIGN recommendations. Of patients admitted for neurological observations, this increased from 50% pre- to 88% post-guidelines. Of patients who were discharged "inappropriately", only one re-presented and was subsequently admitted but required no neurosurgical intervention. Despite publication of the SIGN guidelines and positive reinforcement in A&E and at ward level, practice has not changed significantly. Where our practice did not adhere to SIGN recommendations, there was no untoward sequelae. For published national guidelines to be effective, a formal audit structure with regular feedback is necessary to ensure a continued change in clinical practices.

Craniocerebral Trauma↗
PubMed2005

Asthma during pregnancy: mechanisms and treatment implications.

Asthma is becoming increasingly prevalent worldwide. Numerous historical and prospective cohort studies have investigated the effects of maternal asthma on pregnancy outcome; however, the data has been conflicting and many studies have not used standard classifications for asthma severity. Overall, the literature suggests that asthmatic females are more at risk of low birth weight neonates, pre-term delivery and complications such as pre-eclampsia, especially in the absence of actively managed asthma treated with inhaled corticosteroids. Pregnancy with a female foetus may particularly increase the risk of these outcomes. In addition, pregnancy has an effect on the course of asthma. The risk of an exacerbation requiring medical intervention may be as high as 50% in females with severe asthma and this may further increase the risk of poor outcomes, particularly low birth weight and pre-term delivery. The mechanisms responsible for changes in asthma with pregnancy, or alterations in pregnancy outcomes due to asthma have not been thoroughly explored. Maternal inflammatory pathways may contribute to reduced foetal growth through alterations in placental function. Asthma treatment, by reducing maternal inflammation and preventing exacerbations, is safe for use in pregnant females and contributes to improved outcomes for both mother and foetus.

Asthma↗
PubMed2005

Autologous peripheral blood stem cell transplantation with in vivo T-cell depletion for life threatening refractory systemic lupus erythematosus.

We report the first Australian application of autologous haemopoietic stem cell transplantation in a 39-year old woman with severe systemic lupus erythematosus (SLE) and multiple life threatening complications, refractory to conventional therapy including intravenous cyclophosphamide. Our transplant technique, although not unique, differs from most published reports, in which an unmanipulated peripheral stem cell graft was used with in vivo lymphocyte depletion using rabbit antithymocyte globulin (ATG). Successful stem cell mobilization was achieved using granulocytecolony stimulating factor mobilization with methylprednisolone cover, after an initial attempt at mobilization was curtailed by respiratory arrest from upper airway obstruction due to cricoarytenoiditis, requiring tracheostomy. Conditioning regimen for the transplantation was cyclophosphamide 50 mg/kg on days -5 to -2 and rabbit ATG 2.2 mg/kg on days -3 and -2. An unmanipulated autograft was infused, with in vivo T-cell depletion achieved through a further dose of ATG given on day +2 postinfusion. The autologous transplant was well tolerated without fever or other serious complication. At 12 months follow-up post-transplantation, there is an objective evidence of near-complete response with SLE disease activity index scores falling from 40 pretransplant to 2. We conclude that HSCT with unmanipulated peripheral stem cell graft and in vivo lymphocyte depletion with ATG is safe and effective therapy for cyclophosphamide refractory SLE.

Adult↗
PubMed2005

Role of estrogen receptor (ER) alpha in insulin-like growth factor (IGF)-I-induced responses in MCF-7 breast cancer cells.

Insulin-like growth factor-I (IGF-I) is a mitogenic polypeptide that induces proliferation of MCF-7 breast cancer cells, and cotreatment with the phosphoinositide 3-kinase (PI3-K) inhibitor LY294002 and the antiestrogen ICI 182780 inhibits IGF-I-induced growth. The role of estrogen receptor alpha (ERalpha) in mediating responses induced by IGF-I was investigated in cells transfected with small inhibitory RNA for ERalpha (iERalpha). The results showed that IGF-I-dependent phosphorylation of Akt and mitogen-activated protein kinase, induction of G(1)-S-phase progression and enhanced expression of cyclin D1 and cyclin E were dependent on ERalpha. Moreover, these same IGF-I-induced responses were also inhibited by the antiestrogen ICI 182780 and this was in contrast to a previous report suggesting that ICI 182780 did not affect IGF-I-dependent activation of PI3-K or induction of cyclin D1 expression. ICI 182780 exhibits antimitogenic activity and iERalpha inhibits G(1)-S-phase progression and proliferation of MCF-7 cells treated with IGF-I, suggesting that the effects of the antiestrogen are primarily related to downregulation of ERalpha.

Base Sequence↗
PubMed2005

Microvascular effects of corticotropin-releasing hormone in human skin vary in relation to estrogen concentration during the menstrual cycle.

Females have a significantly greater life expectancy than males, which in part may be due to the cardio-protective effects of the female sex hormone, estrogen, on vascular function. However, the sex-specific mechanisms contributing to these differences are complex and not fully understood. Previously we have reported that corticotropin-releasing hormone (CRH) has potent dilator effects in the female skin circulation via mast cell degranulation. Furthermore the dilator response to CRH was more enhanced in females than in age-matched males, suggesting that estrogens may be involved. In this study we examined whether CRH-induced dilation and endothelial cell-dependent dilation in the skin circulation of pre-menopausal females were associated with changes in estrogen during the menstrual cycle. CRH-induced dilation (1 nM) was enhanced in the presence of high circulating concentrations of estrogen and a positive correlation was identified between CRH-induced dilation and plasma estrogen concentrations. Endothelial cell-dependent dilation was examined using acetylcholine. Acetylcholine-induced dilation (1 nM) was not correlated with circulating concentrations of estrogen. These data suggest the variation in CRH-induced dilation in the skin microvasculature during the menstrual cycle may be due to estrogenic effects on mast cell function and not due to direct changes in endothelial cell function.

Acetylcholine↗