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Biomedical subjects

C Mak

Publications and source records attributed to C Mak.

14 recordsLinked to original sources
PubMed2000

Differential regulation of COX-2 transcription by Ras- and Rho-family of GTPases.

Cyclooxygenase-2 (Cox-2) gene expression which is rapidly induced by cytokines, growth factors and tumor promoters, is important for inflammation, angiogenesis, and is markedly enhanced in various cancer cells. Many of these factors initiate signaling through Ras- and Rho-family small GTPases. Here, we investigated the ability of Ras, Rac, Rho, and Cdc42Hs to differentially regulate transcription from the murine COX-2 promoter in NIH 3T3 cells. Over-expression of constitutively active mutants of Ras, Rac, Rho, but not Cdc42Hs induced transcription from the COX-2 promoter. Transactivation by Rac and Rho required cis-acting elements located between -80 and -40 of the COX-2 promoter whereas deletion of this region enhanced transactivation by Ras. A CRE/ATF element located at -56 was critical for Ras- and Rac-induced transactivation of the COX-2 promoter, but was not required for transactivation by Rho. This demonstrates Rho-dependent transactivation of the COX-2 promoter through novel trans-acting elements and suggests that, in NIH 3T3 cells, signaling by small GTPases that result in COX-2 expression is not through a sequential pathway from Cdc42 to Rac to Rho, but rather through independent, parallel signaling pathways.

3T3 Cells↗
PubMed1999

Interactions of the novel antipsychotic aripiprazole (OPC-14597) with dopamine and serotonin receptor subtypes.

OPC-14597 {aripiprazole; 7-(-4(4-(2,3-dichlorophenyl)-1-piperazinyl) butyloxy)-3,4-dihydro-2(1H)-quinolinone} is a novel candidate antipsychotic that has high affinity for striatal dopamine D2-like receptors, but causes few extrapyramidal effects. These studies characterized the molecular pharmacology of OPC-14597, DM-1451 (its major rodent metabolite), and the related quinolinone derivative OPC-4392 at each of the cloned dopamine receptors, and at serotonin 5HT6 and 5HT7 receptors. All three compounds exhibited highest affinity for D2L and D2S receptors relative to the other cloned receptors examined. Both OPC-4392 and OPC-14597 demonstrated dual agonist/antagonist actions at D2L receptors, although the metabolite DM-1451 behaved as a pure antagonist. These data suggest that clinical atypicality can occur with drugs that exhibit selectivity for D2L/D2S rather than D3 or D4 receptors, and raise the possibility that the unusual profile of OPC-14597 in vivo (presynaptic agonist and postsynaptic antagonist) may reflect different functional consequences of this compound interacting with a single dopamine receptor subtype (D2) in distinct cellular locales.

Animals↗
PubMed1999

Nursing as a career choice: perceptions of school students speaking Arabic, Serbo-Croatian, Spanish, Turkish or Vietnamese at home.

Australia is a multicultural society and nowhere is this more evident than in Sydney where 25% of the population speaks a language other than English. In one of the largest area health services in New South Wales, the five most frequently spoken languages at home are Arabic, Serbo-Croatian, Spanish, Turkish or Vietnamese, with these language groups comprising 12% of Sydney's population. Yet nurses speaking one of these five languages comprise less than 1% of the nursing workforce. A cost-effective method of addressing the shortage of nurses speaking languages other than English is to recruit students who already speak another language into the profession. This study examined high school students' perceptions of nursing in order to determine appropriate methods of recruiting students speaking one of these languages. Implications for the design of recruitment campaigns are also discussed.

Attitude to Health↗
PubMed1999

Tuning friction with noise and disorder.

We present numerical and experimental evidence which demonstrates that under certain conditions friction can be reduced by spatial disorder and/or thermal noise. We discuss possible mechanisms for this behavior.

Journal Article↗
PubMed1998

neu/erbB-2 amplification identifies a poor-prognosis group of women with node-negative breast cancer. Toronto Breast Cancer Study Group.

PURPOSE: It remains a challenge to predict which women with axillary node-negative (ANN) breast cancer at greatest risk of relapse may benefit most from adjuvant therapy. Increases in neu/erbB-2 have been implicated in breast cancer prognosis. Although overexpression has been investigated extensively, this study represents the first prospective assessment of the prognostic value of neu/erbB-2 DNA amplification in a cohort of women with newly diagnosed ANN. METHODS: A consecutive series of women was monitored for recurrence (median follow-up duration, 36 months) and tumors from 580 individuals were analyzed for amplification. The association of amplification with risk of recurrence was examined in survival analyses with traditional and histologic markers as prognostic factors. RESULTS: Neu/erbB-2 was amplified in 20% of cases. We found an increased risk of disease recurrence when neu/erbB-2 was amplified > or = twofold that persisted with adjustment for other prognostic factors (relative risk, 2.36; P = .002). We found some evidence that amplification was more important in patients who received chemotherapy compared with untreated patients. CONCLUSION: neu/erbB-2 amplification is an independent prognostic factor for risk of recurrence in ANN breast cancer. Women with tumors without neu/erbB-2 amplification have a good prognosis; aggressive therapy in this group is therefore difficult to justify. On the other hand, even with adjuvant chemotherapeutic treatment, women whose tumors exhibit neu/erbB-2 amplification have an increased risk of recurrence. We encourage a randomized trial to compare more aggressive adjuvant chemotherapy versus standard chemotherapy for ANN women whose tumors exhibit neu/erbB-2 amplification.

Axilla↗
PubMed1996

Getting the most from outsourcing.

Outsourcing is common in the business world for its cost saving benefits. This article examines outsourcing as it is used in the Hong Kong healthcare setting for security services and assesses its outcomes in terms of cost, quality, performance, and control. The author reports on several management problems, and makes suggestions for effective outsourcing practices. Hospitals are advised to prepare and manage their contracts as if they were run in-house. Administrators who manage hospitals must examine their operations and try to add value to services where applicable, including outsourced services.

Competitive Bidding↗
PubMed1995

Successful people selection in action.

As a people-intensive industry, the health care service should invest both time and resource in attracting, selecting and retaining its staff. Highlights the fact that the traditional interview is a poor selection tool. Outlines a systematic approach to hiring people and describes the structured behaviour interview tool. Explains the tool using a recent recruitment exercise in the health-care setting. Concludes that line management should play an active role in staff selection and organizations should look for better approach and tools to improve their hiring effectiveness.

Hong Kong↗
PubMed1989

Comparative in vitro myocardial inotropic effects and in vivo hemodynamic effects of forskolin and isoproterenol in young lambs.

Previous studies have shown a decreased responsiveness of young lambs to isoproterenol, a beta-adrenergic agonist, when compared to older lambs. To see if this decreased responsiveness of immature lambs is secondary to an abnormality of the beta-adrenergic receptor/adenylate cyclase complex, we compared the effects of isoproterenol to forskolin, a direct activator of the catalytic subunit of adenylate cyclase. In isometrically contracting right ventricular trabeculae from five lambs (5-13 d old), the maximal developed tension with isoproterenol (875 +/- 84 mg, mean +/- SD) and forskolin (704 +/- 189 mg) was similar. However, the median effective dose for isoproterenol (5.3 +/- 3.4 X 10(-7) M) was significantly less than the minimal median effective dose for forskolin (2.5 +/- 1.3 X 10(-6) M) indicating a lesser sensitivity to forskolin. In eight conscious resting lambs (4-13 d old) we measured the hemodynamic response to graded infusions of isoproterenol and forskolin. At maximal dosage, the increase in cardiac output was significantly greater with isoproterenol (+130%) than forskolin (+55%). Heart rate also increased more with isoproterenol than forskolin. These data show that direct stimulation of adenylate cyclase in young lambs does not provide better inotropic or chronotropic responses than beta-adrenergic stimulation with isoproterenol. This suggests that the decreased beta-adrenergic responsiveness in newborn lambs is secondary to abnormalities that exist beyond the level of the beta-adrenergic receptor/adenylate cyclase complex.

Animals↗
PubMedDate not supplied

Nonlinear analysis of partial dopamine agonist effects on cAMP in C6 glioma cells.

Most drugs have some efficacy so that improved methods to determine the relative intrinsic efficacy of partial agonists should be of benefit to preclinical and clinical investigators. We examined the effects of partial D(1) or partial D(2) dopamine agonists using a partial agonist interaction model. The dependent variable was the modulation of the dopamine-receptor-mediated cAMP response in C6 glioma cells selectively and stably expressing either D(1) or D(2) recombinant dopamine receptors. The dissociation constant (K(B)) and relative intrinsic efficacy (E(r)) for each partial agonist were calculated using a partial agonist interaction null model in which the effects of fixed concentrations of each partial agonist on the dopamine dose-response curve were evaluated. This model is an extension of the competitive antagonist null model to drugs with efficacy and assumes only that the log-dose--response curve is monotonic. Generally, the partial agonist interaction model fit the data, as well as fits of the independent logistic curves. Furthermore, the partial agonist K(B) values could be shared across partial agonist concentrations without worsening the model fit (by increasing the residual variance). K(B) values were also similar to drug affinities reported in the literature. The model was validated in three ways. First, we assumed a common tissue stimulus parameter (beta) and calculated the E(r) values. This provided a qualitative check on the interaction model results. Second, we calculated new relative efficacy values, E(r)(beta), using the beta estimate. Third, we calculated relative efficacy using relative maxima times midpoint shift ratios (J. Theor. Biol. 198 (1999) 347.). All three methods indicated that the present model yielded reasonable estimates of affinity and relative efficacy for the set of compounds studied. Our results provide a quick and convenient method of quantification of partial agonist efficacy. Special applications and limitations of the model are discussed. In addition, the present results are the first report of the relative intrinsic efficacy values for this set of D(2) ligands.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMedDate not supplied

Human sperm movement assessed with the Hamilton-Thorn motility analyzer and in vitro fertilization.

UNLABELLED: The relationship between sperm movement characteristics obtained by computerized analysis and the in vitro fertilization rates of human oocytes was studied. In 144 consecutive in vitro fertilization treatments a sample of prepared semen was analysed by a Hamilton-Thorn Motility Analyzer. In addition a visual estimation of sperm count and motility was made. Significant correlations with the fertilization rate were found for all visual parameters. Of the computerized measurements, the mean velocities of motile spermatozoa and the concentration of motile cells were significantly correlated. The average path velocity correlated best (r = 0.42, P < 0.001). There was no relationship between the percentage of motile sperm showing hyperactivated movement and the fertilization rate. A forward stepwise logistic regression analysis selected the following variables of predictive value for fertilization: average path velocity, male factor infertility as indication for in vitro fertilization, motility and concentration, as measured by the Hamilton-Thorn analyzer. A logistic regression model to predict the cases with low (< 0.2) or high fertilization rates, included the average path velocity as a significant variable and classified the samples with 90% overall accuracy. IN CONCLUSION: movement characteristics of spermatozoa in culture medium, especially the average path velocity are of prognostic value in prediction of human oocyte fertilization rates.

Computers↗
PubMedDate not supplied

Predictors of intention to study nursing among school students speaking a language other than English at home.

There is currently a shortage of bilingual nurses in New South Wales. It is important to include bilingual nurses in the workforce to meet not only the cultural and social needs of people speaking a language other than English at home, but also to facilitate the achievement of appropriate health outcomes for a multicultural population. The purpose of this study was to identify demographic and social factors which explain students' intention to study nursing. Respondents were 789 year 11 or 12 students speaking Arabic, Serbo-Croatian, Spanish, Turkish or Vietnamese from twenty-five schools in South Eastern, South Western and Western Sydney. Data were collected through a self-completed questionnaire. Chi square, t-test and logistic regression analysis were used for data analysis. Logistic regression analysis concluded that perceived parental income, years of settlement in Australia and father's occupation were significant factors. Bivariate analysis also revealed that significant differences were found in the intention to study nursing between male and female students and between students with a higher and lower Tertiary Entrance Rank (TER). Parental influence also affects students' intention. However, gender and TER were found to be insignificant after adjustment for other variables in the logistic regression model.

Adolescent↗