Biomedical subjects
Publications and source records attributed to J M Young.
As dental clinicians, common sense is still the best weapon for infection control--the use of antimicrobial cleaning products remains an integral component of any infection control procedure.
SK&F 96365 (1-[beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenylethyl]-1H-imi dazole hydrochloride) stimulated the accumulation of [3H]inositol monophosphates ([3H]IP1) in human U373 MG astrocytoma cells prelabelled with [3H]inositol (EC50 15 +/- 1 microM, Hill coefficient 3.8 +/- 0.4). SK&F 96365-induced accumulation of [3H]IP1 increased linearly with time, but there was no initial rapid formation of [3H]IP3. SK&F 96365 also stimulated [3H]IP1 accumulation in human HeLa cells, but only to a small extent in slices of rat cerebral cortex and guinea-pig cerebellum. SK&F 96365-induced accumulation of [3H]IP1 in U373 MG cells increased as extracellular Ca2+ was increased from nominally zero to 4 mM, but there was no evidence that SK&F 96365 induced any marked entry of Ca2+ into cells; only an inhibition of store-refilling-induced Ca2+ entry was apparent. Further, the response to SK&F 96365 was additive with that to the Ca2+ ionophore ionomycin. Depolarization of the cells with raised K+ produced only a small stimulation of phosphoinositide hydrolysis. SK&F 96365 caused the release of Ca2+ from intracellular stores in U373 MG cells (EC50 26 +/- 14 microM), but thapsigargin induced only a small accumulation of [3H]IP1. Miconazole, another N-substituted imidazole, also stimulated [3H]IP1 accumulation in U373 cells.
OBJECTIVE: To determine current beliefs and knowledge about, and use of, two screening tests for breast cancer (mammography and clinical breast examination [CBE]) among general practitioners (GPs). DESIGN, PARTICIPANTS AND SETTING: National postal survey of randomly selected GPs from throughout Australia in May 1996. MAIN OUTCOME MEASURES: Belief in the effectiveness of each screening test in reducing premature deaths from breast cancer; recommended age group and screening interval for each test; likelihood of including each opportunistically or in a health check-up. Predictors were determined by regression analyses. RESULTS: The response rate was 67% (855/1271). Significantly more respondents believed in the effectiveness of mammography than of CBE (92% v. 66%). About half identified women 50 years and over as the appropriate target group for mammography. Only 40% indicated they would be "highly likely" to discuss mammography opportunistically, although 82% would be "highly likely" to discuss it in a health check-up. After adjusting for confounders, female GPs were more likely to discuss mammographic screening and to advocate a biennial frequency. Older GPs and those from New South Wales were least likely to recommend mammography (consistent with the national policy). Significantly more respondents were "highly likely" to discuss CBE than mammography in a health check-up. CONCLUSIONS: GPs are convinced of the effectiveness of mammography, but as respondents were more likely to screen by CBE than to recommend mammography in a dedicated health check-up a consistent national policy about CBE would be highly desirable.
The immunoregulatory functions of IL-4 and IL-5 have identified these cytokines as primary targets for the resolution of airways inflammation and bronchial hyperreactivity in asthma. However, the individual contribution of each of these cytokines and of IL-5-regulated eosinophilia to the induction of airways hyperreactivity in mouse models of asthma remains highly controversial. In this investigation, we have used IL-4- and IL-5-deficient mice of the same genetic background in combination with inhibitory mAbs to these cytokines to identify unequivocally the contribution of these factors to the induction of airways hyperreactivity. Sensitization and aeroallergen challenge of wild-type mice with OVA induced pathological changes to the respiratory epithelium, airways eosinophilia, and hyperreactivity to beta-methacholine. Inhibition of the actions of IL-4 and/or IL-5 did not abolish airways hyperreactivity, and in the case of IL-4-deficient mice pretreated with anti-IL-5 mAb, airways hyperreactivity persisted in the absence of pronounced airways inflammation. Airways hyperreactivity was abolished only by anti-CD4+ mAb treatment. However, aeroallergen challenge of IL-5-/- mice showed that morphologic changes to the airways were critically linked to IL-5 and eosinophilia. This investigation demonstrates the existence in BALB/c mice of a novel CD4+ T cell pathway for modulating airways hyperreactivity. These findings may provide an explanation for the dissociation of airways eosinophilia from the development of airways hyperreactivity observed in some cases of asthma and in animal models of this disease.
1. In human U373 MG astrocytoma cells agonist-induced increases in intracellular Ca2+ ([Ca2+]i) are rapidly returned towards prestimulated levels. Examination of the effect of histamine and substance P on [Ca2+]i in thapsigargin-treated cells has allowed a mechanism contributing to this effect to be characterized. 2. Histamine and substance P stimulated [3H]-inositol monophosphate ([3H]-IP1) accumulation in U373 MG cells. Concentration-response curves of [3H]-IP1 accumulation in suspensions of U373 MG cells in HEPES buffer containing 30 mM Li+ yielded best-fit EC50 values of 19.1+/-1.5 microM for histamine and 5.7+/-1.3 nM for substance P. 3. In confluent monolayers of fura-2 loaded U373 MG cells perfusion with 100 microM histamine resulted in a transient 597+/-50 nM increase in [Ca2+]i. The best-fit EC50 for histamine was 4.6+/-2.2 microM. The initial, transient, histamine response was often followed by further small transient increases in [Ca2+]i. 4. Treatment of U373 MG cells with 5 microM thapsigargin, followed by the readdition of 1.8 mM Ca2+ to the perfusion buffer, resulted in a steady-state level of [Ca2+]i 97+/-5 nM above pretreated levels (measured 400 s after readdition of Ca2+). Perfusion of histamine (100 microM, 100 s) caused a rapid decline in the thapsigargin-induced steady state level of [Ca2+]i. This effect of histamine was normally reversible upon washout. The best-fit EC50, for the histamine response was 0.8+/-0.2 microM. Substance P (10 nM, 100s) also caused a reduction in thapsigargin-induced steady-state levels of [Ca2+]i. 5. Neither 100 microM histamine nor 10 nM substance P inhibited the rate of quench of fura-2 fluorescence by Mn2+ in U373 MG cells pretreated with 5 microM thapsigargin, indicating that the depressant effect on steady-state raised [Ca2+]i was probably not due to a block of Ca2+ entry. 6. The depressant effect of histamine on [Ca2+]i was blocked by 1 microM mepyramine, and was partially reduced by pre-incubation with 1 microM staurosporine (61+/-7% reduction) and with Ro 31-8220 (24+/-10% and 50+/-6% reduction by 1 and 10 microM Ro 31-8220, respectively). Pre-incubation with H-89 did not alter the depressant effect of histamine. 7. Neither 1 microM staurosporine nor 10 microM KN-62 inhibited the binding of [3H]-mepyramine to guinea-pig cerebellar membranes, whereas it was reduced by 17+/-1% and 55+/-2% by 1 and 10 microM Ro 31-8220, respectively. However, [3H]-IP1 accumulation stimulated by histamine in U373 MG cells was not inhibited by 1 or 10 microM Ro 31-8220 and in 2 out of 3 experiments there was a significant potentiation of the response to histamine with both concentrations of Ro 31-8220. Staurosporine, 1 microM, similarly potentiated the response to 100 microM histamine in 3 out of 4 experiments. KN-62 (10 microM) did not stimulate histamine-induced [3H]-IP1 accumulation. 8. In HEPES buffer to which no Ca2+ had been added, histamine stimulated a transient 451+/-107 nM increase in [Ca2+]i. Pretreatment with 1 microM and 10 microM Ro 31-8220 did not significantly alter the initial peak response to histamine, but slowed the rate at which histamine-induced increases in [Ca2+]i were returned to prestimulated levels. Pretreatment with KN-62 had no significant effect on the response to histamine, but consistently inhibited the secondary slower phase of the decline in [Ca2+]i. H-89 did not alter the histamine response. 9. The effect of histamine in stimulating Ca2+ extrusion was not confined to U373 MG cells, since 100 microM histamine also caused a rapid decrease in steady-state levels of [Ca2+]i in thapsigargin-treated human HeLa cells. 10. The results indicate that agonists which increase [Ca2+]i via activation of phosphoinositide metabolism can also stimulate a homeostatic mechanism which acts to reduce [Ca2+]i. The balance of the evidence indicates that in U373 MG cells the latter effect most likely involves a PKC-mediated stimulation of a Ca2+-extrusion pump.
Antibacterial and antifungal activity was investigated for strains of Acidovorax spp., Burkholderia spp., Herbaspirillum rubrisubalbicans and Ralstonia solanacearum; strains representing 118 species and pathovars of Xanthomonas were also tested for phytotoxic capacity. Antibacterial activity was present in all Burkholderia spp. except B. andropogonis, in biovars II and III of R. solanacearum but not in biovars I and IV, and in two strains of Xanthomonas. Little antibacterial activity was recorded for Acidovorax spp. Antifungal activity was expressed by most strains of A. avenae ssp. avenae and A. avenae ssp. cattleyae. Weak or variable antifungal reactions were given by strains of A. avenae ssp. citrulli and no activity was expressed by A. konjaci. Most strains of B. caryophylli, B. cepacia, B. gladioli pv. agaricicola, B. gladioli pv. alliicola, B. gladioli pv. gladioli, B. glumae and B. plantari produced extensive inhibition zones against Rhodotorula mucilaginosa. Strains of H. rubrisubalbicans and R. solanacearum gave negative, weak or variable reactions. Strains of Xanthomonas spp. exhibited no antifungal activity. In all cases antifungal activity was caused by a low molecular weight toxin. Three Xanthomonas strains exhibited phytotoxic activity. The ecological implications of these data are discussed.
Strains representing the fluorescent plant pathogenic Pseudomonas spp., Ps. agarici, Ps. asplenii, Ps. avellanae, Ps. beteli, Ps. caricapapayae, Ps. cichorii, Ps. corrugata, Ps. ficuserectae, Ps. flectens, Ps. fuscovaginae, Ps. marginalis, Ps. meliae, Ps. savastanoi, Ps. syringae, Ps. tolaasii and Ps. viridiflava were tested for biocidal activity using Aspergillus niger as assay organism. Inhibitory behaviour was found in strains of Ps. asplenii, Ps. blatchfordae, Ps. cichorii, Ps. corrugata, Ps. fuscovaginae, Ps. marginalis, Ps. marginalis pv. pastinacea, Ps. syringae pv. syringae, Ps. syringae pv. aptata, Ps. syringae pv. atrofaciens, Ps. syringae pv. lapsa, Ps. tolaasii, and strains of a Pseudomonas sp. pathogenic to Actinidia, in the Ps. savastanoi genomic sp. Antifungal activity could be identified with the production of members of the syringomycin family of toxins by strains in Ps. syringae, Ps. asplenii and Ps. fuscovaginae. These toxin reactions support suggestions made elsewhere of the synonym of the latter two species. In a preliminary characterization using tests for stability to heat, protease, acid and alkaline treatments, unknown toxins consistent with syringomycin-like toxins the strains from Actinidia species. The toxins from Ps. cichorii and from Ps. corrugata differed in their reactions from all other agents. Pseudomonas tolaasii produces the antifungal compound tolaasin. The white line reaction with Ps. reactions, a test for tolaasin production by strains of Ps. tolaasii, was confirmed as specific for this compound. Some of these low molecular weight toxins may be produced by some of these plant pathogenic strains.
Airway inflammation is central to the pathogenesis of allergic asthma, and molecules that mediate this process obviously represent targets for therapy. In the present article, we discuss our experiments, which point to CD4+ T cells and IL-5-driven eosinophilia as potential targets for the relief of bronchial hyperreactivity in late-phase asthma.
The entire coding region of the TSC1 gene has been screened for mutations in 79 unrelated patients with tuberous sclerosis. Causative mutations have been found in 27 of these patients and five other variations in the gene have been identified. 26 of the mutations are predicted to cause premature truncation of the protein product of the gene and one mutation is in a splice site. The mutation screen has revealed that TSC1 mutations are rarer in sporadic tuberous sclerosis patients than in familial cases. We have also found that the only previously described case of non-penetrance can no longer be described as such, and that a single ungual fibroma is not necessarily diagnostic of tuberous sclerosis, important findings for the genetic counselling of tuberous sclerosis patients.
We investigated the regulation by intracellular Ca2+ of agonist-induced sequestration of Gq protein-coupled histamine H1 receptors in human U373 MG astrocytoma cells. Histamine-induced sequestration of H1 receptors from the cell surface membrane was detected as the loss of [3H]mepyramine binding sites on intact cells accessible to the hydrophilic H1-receptor antagonist pirdonium. The changes in the pirdonium-sensitive binding of [3H]mepyramine were mirrored by changes in the subcellular distribution of H1 receptors detected by sucrose density gradient centrifugation. The histamine-induced sequestration of H1 receptors did not occur in hypertonic medium, in which clathrin-mediated endocytosis is known to be inhibited, but was significantly accelerated in the absence of extracellular Ca2+ or in the presence of the calmodulin antagonists W-7 and calmidazolium. Inhibitors of protein kinase C (H-7 and GF109203X), Ca2+/calmodulin-dependent protein kinase II (KN-62), or protein phosphatase 2B (FK506) did not alter the time course of H1-receptor sequestration. These results provide the first evidence that agonist-induced, clathrin-mediated sequestration of Gq protein-coupled receptors is transiently inhibited by Ca2+/calmodulin, with the result that receptors remain on the cell surface membrane during the early stage of agonist stimulation.
The study discussed in this article describes the nature of positive life experiences of 13 people coping exceptionally well while living with advanced amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease, and the resulting significant physical disability. The most powerful themes to emerge were the use of cognitive reappraisal, reframing, and intellectual stimulation as coping mechanisms; the development of wisdom; and the vital importance of interpersonal relationships. On the basis of our findings, we make suggestions for ways professionals can assist people with ALS and their significant others.
Smoking cessation advice from a general practitioner (GP) significantly increases quit rates among patients who smoke. However, smoking is not discussed during most routine consultations with smokers. This study describes GPs' own views about strategies to support their cessation advice. In 1997, a random sample of 311 GPs in NSW (73% response rate) completed a self-administered questionnaire about smoking cessation. Most respondents were 'very confident' about discussing the health effects of smoking (81.7%). Fewer were as confident about negotiating a quit date (21.5%) or using evidence-based smoking cessation techniques (19.3%). The top three preferred strategies to support smoking cessation advice were all resources for patients: subsidised nicotine replacement therapy (rated as 'quite useful' by 60.5%), pamphlets (55.0%) and free access to smoking cessation clinics (50.8%). Skills training (39.7%) was the preferred resource to improve practitioner effectiveness. Interventions combining skills training with patient resources are likely to be well received by GPs.
OBJECTIVE: To examine the association between physician and patient gender and physicians' self-reported likelihood of providing smoking cessation advice to smokers using hypothetical case scenarios in primary care. DESIGN: Cross-sectional analysis of a self-administered questionnaire. SUBJECTS: National random sample of Australian general practitioners (GPs). MAIN OUTCOME MEASURES: Self-reported likelihood of advising hypothetical male and female smokers to stop smoking during a consultation for ear-syringing ("opportunistic" approach) or a dedicated preventive health "check up". RESULTS: 855 GPs returned questionnaires (67% response rate). Significantly more respondents indicated they would be "highly likely" to initiate an opportunistic discussion about smoking with a male smoker (47.8% (95% confidence intervals (CI) = 44.5 to 51.2)) than a female smoker (36.3% (95% CI = 33.1 to 39.5]). Older, male GPs were less likely to adopt an opportunistic approach to smoking cessation for patients of either sex. Respondents were more likely to recommend that a male patient return for a specific preventive health check up. Furthermore, in the context of a health check up, a greater proportion in total of respondents indicated they would be "highly likely" to discuss smoking with a man (86.9%, 95% CI = 84.5 to 89.0) than a female smoker (82.5%, 95% CI = 79.8 to 84.9). CONCLUSIONS: As measured by physician self-report, the likelihood of advising smokers to quit during primary care consultations in Australia appears to be influenced by gender bias. Gender-sensitive strategies to support cessation activities are recommended.
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The release of [3H]GABA from slices of rat substantia nigra pars reticulata induced by increasing extracellular K+ from 6 to 15 mM in the presence of 10 microM sulpiride was inhibited by 73 +/- 3% by 1 microM SCH 23390, consistent with a large component of release dependent upon D1 receptor activation. The histamine H3 receptor-selective agonist immepip (1 microM) and the non-selective agonist histamine (100 microM) inhibited [3H]GABA release by 78 +/- 2 and 80 +/- 2%, respectively. The inhibition by both agonists was reversed by the H3 receptor antagonist thioperamide (1 microM). However, in the presence of 1 microM SCH 23390 depolarization-induced release of [3H]GABA was not significantly decreased by 1 microM immepip. In rats depleted of dopamine by pretreatment with reserpine, immepip no longer inhibited control release of [3H]GABA, but in the presence of 1 microM SKF 38393, which produced a 7 +/- 1-fold stimulation of release, immepip reduced the release to a level not statistically different from that in the presence of immepip alone. Immepip (1 microM) also inhibited the depolarization-induced release of [3H]dopamine from substantia nigra pars reticulata slices, by 38 +/- 3%. The evidence is consistent with the proposition that activation of histamine H3 receptors leads to the selective inhibition of the component of depolarization-induced [3H]GABA release in substantia nigra pars reticulata slices which is dependent upon D1 receptor activation. This appears to be largely an action at the terminals of the striatonigral GABA projection neurons, which may be enhanced by a partial inhibition of dendritic [3H]dopamine release.
In restructuring from a departmental to a program management model, BC Rehab successfully developed the role of professional practice leader to address clinical standards of practice and other concerns related to individual disciplines. A review of the role of professional practice leader is presented. Practice leaders are in a unique position to promote interdisciplinary, client-focused service. Because practice leaders' mandates cross program boundaries, they are able to keep the broad scope and goals of rehabilitation in the forefront, offering a balance to the program-specific perspective. It is imperative for practice leaders to maintain connections to operational and clinical issues to avoid isolation.
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