Glucocorticoid and cyclic adenosine 3'5'-monophosphate-mediated induction of cholesterol side-chain cleavage cytochrome P450 (P450scc) in MA-10 tumor Leydig cells. Increases in mRNA are cycloheximide sensitive

The regulation of cholesterol side-chain cleavage enzyme (P450scc) was investigated in MA-10 tumor Leydig cells. We recently demonstrated that the constitutive and cAMP-stimulated expression of P450scc in normal mouse Leydig cells is negatively regulated by glucocorticoids. We now report that glucocorticoids have the opposite effect in MA-10 cells causing a 1.7-fold increase in the rate of P450scc synthesis and a 2.1-fold increase in the amount of P450scc mRNA. Treatment of MA-10 cells with 10 microM 8-bromo-cAMP (8-Br-cAMP) (cAMP) resulted in a 1.7-fold increase in P450scc synthesis and a 3-fold increase in P450scc mRNA. Combined treatment with dexamethasone and cAMP resulted in additive increases in synthesis (2.8-fold) and mRNA (5.3-fold). Increases in de novo synthesis and mRNA levels were reflected by modest increases in the amount of immunoreactive P450scc enzyme protein. Dexamethasone-mediated stimulation in synthesis and accumulation of P450scc mRNA were blocked by the antiglucocorticoid RU-486. Cycloheximide blocked both cAMP- and dexamethasone-induced increases but had no effect on constitutive levels of P450scc mRNA. Treatment of MA-10 cells with 10 microM 8-Br-cAMP had no effect on cell morphology and stimulated progesterone accumulation to a minor degree. Treatment of MA-10 cells with 1 mM 8-Br-cAMP resulted in cell rounding and loss of cells from culture dishes. The results of this study demonstrate that: 1) dexamethasone increases P450scc de novo synthesis and mRNA levels in MA-10 tumor Leydig cells, opposite to the effect in normal Leydig cells; 2) dexamethasone- and cAMP-stimulated increases occur via distinct mechanisms; 3) and synthesis of protein factor(s) is required to mediate the action of both dexamethasone and cAMP.     

Parental resilience: A neglected construct in resilience research

The substantial focus of resilience research on childhood well‐being has resulted in limited knowledge regarding other aspects of resilience in families, such as that of parents. Informed by literature in childhood and family resilience, in this review, we progress conceptual understanding by focusing on parental resilience. The definition of parental resilience, as the capacity of parents to deliver a competent and quality level of parenting to children despite the presence of risk factors, is offered here as a worthwhile framework through which to explore variables thought to contribute to resilience among parents. A conceptual model is proposed whereby parental psychological well‐being and self‐efficacy, family functioning, and social connectedness are specifically addressed, with each posited as playing an important role in parents’ ability to deliver high‐quality parenting. In addition to these factors, how parents accommodate adversity and find meaning in their everyday lives within their families is hypothesised to be an important process in understanding parental resilience.     

Theileria parva piroplasmosis in mice, and its attempted transmission with Rhipicephalus appendiculatus ticks.

Theileria parva piroplasm infection of mouse erythrocytes was detected, following intraperitoneal inoculation of mice with irradiated cultures of T. parva-infected bovine lymphoid cells. Infection could not be transmitted to cattle using Rhipicephalus appendiculatus ticks.     

Subclinical right ventricular dysfunction in cystic fibrosis. A study using tissue Doppler echocardiography

Patients with severe cystic fibrosis can develop cor pulmonale, but little is known about the function of the right ventricle (RV) early in the disease. We hypothesized that such patients might have subclinical RV dysfunction, detectable by tissue Doppler echocardiography, and related to the severity of lung disease. We studied 21 clinically stable patients (Group 1), five patients with severe lung disease (Group 2), and 23 age-matched healthy subjects. Patients had impaired RV systolic function. The mean (SD) systolic velocities of the RV free wall were 8.9 (1.7) cm/s in Group 1, 7.7 (1.0) in Group 2, and 10.8 (1.9) in healthy subjects (p < 0.001). The velocities of the tricuspid annulus were less in patients (p < 0.0001). Patients had a greater isovolumic relaxation time (p < 0.001), indicating RV diastolic dysfunction. RV wall thickness was greater in patients (0.4 [0.1] versus 0.3 [0.1] cm/m(2), p < 0.01). RV systolic function was related to C-reactive protein (r = - 0.66, p < 0.001) and FEV(1) (r = 0.62, p = 0.003) and diastolic function to interleukin-6 (r = 0.64, p < 0.005). Patients with cystic fibrosis have subclinical RV dysfunction, which correlates with the severity of lung disease. Tissue Doppler echocardiography provides a quantifiable indicator useful for detection and monitoring of disease progression.     

Is intimal hyperplasia a marker of neuro-ophthalmic complications of giant cell arteritis?

Objective. The ischaemic complications of giant cell arteritis(GCA) such as blindness and stroke may result from luminal narrowingof the affected arteries. This study focuses on the associationbetween the severity of intimal proliferation on temporal arterybiopsy (TAB) histology and neuro-ophthalmic complications (NOCs)of GCA. Method. We identified 30 cases of biopsy-proven temporal arteritis.One histopathologist (blinded to the clinical details) evaluatedthe TAB specimens and categorized the degree of maximum stenosisdue to intimal hyperplasia into four grades: grade 1 is <50%luminal occlusion due to intimal hyperplasia, grade 2 is 50–75%,grade 3 is >75% and grade 4 is complete luminal occlusion.A second histopathologist (also blinded to the clinical details)independently evaluated the TAB specimens using the same gradingsystem. The NOCs in these patients were noted after a case recordreview. Results. Of the 30 patients, 12 had NOC-10 with eye complications(complete visual loss, anterior ischaemic neuropathy, visualfield defects), one patient had cerebral infarcts and one hadboth cerebral infarcts and vision loss. There was evidence fora statistically significant trend of NOC associated with higherintimal hyperplasia scores (P = 0.001). The scores of the histopathologistsagreed for 23 (77%) patients and differed by 1 category forthe remaining 7 (-statistic 0.88). Conclusions. Our study suggests that the degree of intimal hyperplasiaon TAB histology (routinely available to all hospital units)seems to be closely associated with NOCs of GCA. The study highlightsthe possible prognostic as well as diagnostic role of the biopsy.We feel that intimal hyperplasia noted in biopsy specimens mayhelp us in the risk stratification of GCA patients and targetingof appropriate and novel therapies. KEY WORDS: Intimal hyperplasia, Giant cell arteritis, Neuro-ophthalmic complications Submitted 1 June 2007; revised version accepted 7 January 2008.     

Clustering Individuals as a Way of Dealing with Multiple Predictors in Occupational Stress Research

Abstract

As the number and type of variables thought to affect the amount of stress experienced by an individual in the workplace increase, and as these effects are often found to be nonlinear and to interact with each other, the forms of statistical analyses employed present different costs and benefits. The use of cluster analysis as a preliminary means of categorizing individuals is described as the least artificial and empirically most accurate means of deriving groups that can lead to hypotheses and hypothesis testing using the more conventional means of analysis of variance. Such a methodology is described as it was applied to an investigation of the effects of demands, attitudes to demands, supports-constraints, and trait neuroticism upon job satisfaction and scores on the General Health Questionnaire for a sample of psychiatric nurses.