Relationship of XIST expression and responses of ovarian cancer to chemotherapy

Expression profiling to characterize cancer pharmacology has become a new approach to discover novel molecular targets for prognostic markers and cancer therapy. In a study to compare the global RNA expression profiles between primary and recurrent ovarian tumors from the same patient, we have identified XIST (inactive X chromosome-specific transcripts) as the most differentially expressed gene that was down-regulated in the recurrent tumor. XIST encodes a spliced noncoding polyadenylated transcript that is unique in being expressed exclusively from the inactive X chromosome and is involved in the X-inactivation process. Subsequent characterization of XIST expression in a panel of female cancer cell lines showed that the expression level of XIST correlates significantly with Taxol sensitivity. The clinical relevance of this observation is demonstrated by the strong association between XIST RNA levels and disease-free periods of ovarian cancer patients in a group of 21 ovarian cancer cases with Taxol in the therapeutic regiments. Cytogenetic studies on ovarian cancer cell lines indicated that loss of inactive X chromosome is one mechanism for the loss of XIST transcripts in the cell lines. Our data suggest that XIST expression may be a potential marker for chemotherapeutic responses in ovarian cancer.

Assessment of the ability to model proteins with leucine-rich repeats in light of the latest structural information

The three-dimensional structures of leucine-rich repeat (LRR) -containing proteins from five different families were previously predicted based on the crystal structure of the ribonuclease inhibitor. using an approach that combined homology-based modeling, structure-based sequence alignment of LRRs, and several rational assumptions. The structural models have been produced based on very limited sequence similarity, which, in general. cannot yield trustworthy predictions. Recently, the protein structures from three of these five families have been determined. In this report we estimate the quality of the modeling approach by comparing the models with the experimentally determined structures. The comparison suggests that the general architecture, curvature, interior/exterior orientations of side chains. and backbone conformation of the LRR structures can be predicted correctly. On the other hand. the analysis revealed that, in some cases. it is difficult to predict correctly the twist of the overall super-helical structure. Taking into consideration the conclusions from these comparisons, we identified a new family of bacterial LRR proteins and present its structural model. The reliability of the LRR protein modeling suggests that it would be informative to apply similar modeling approaches to other classes of solenoid proteins.

Expert review of an approach to functional capacity evaluation

Functional capacity evaluation (FCE) is a widely used tool in work rehabilitation, despite the limited examination of the soundness of its measurement properties. This paper outlines the development of a new approach to FCE, the GAPP FCE, and reports on the findings of an expert review of aspects of its content validity and technical adequacy and how it meets established test criteria. Five expert occupational therapists reviewed the materials of the GAPP FCE then completed a questionnaire related to the content validity, technical adequacy and safety, reliability, validity, practicality and utility of the GAPP FCE. The experts gave support to most aspects of these criteria. The main issue identified by the review was related to interpretation and extrapolation of the FCE results for return to work. This and other issues are discussed in relation to recent developments in FCE and plans for future development of the GAPP FCE.

Calorimetric demonstration of the potential of molecular crowding to emulate the effect of an allosteric activator on pyruvate kinase kinetics

A method based on isothermal calorimetry is described for the direct kinetic assay of pyruvate kinase. In agreement with earlier findings based on the standard coupled assay system for this enzyme in the presence of a fixed ADP concentration, the essentially rectangular hyperbolic dependence of initial velocity upon phosphoenolpyruvate concentration is rendered sigmoidal by the allosteric inhibitor phenylalanine. This effect of phenylalanine can be countered by including a high concentration of a space- filling osmolyte such as proline in the reaction mixtures. This investigation thus affords a dramatic example that illustrates the need to consider potential consequences of thermodynamic nonideality on the kinetics of enzyme reactions in crowded molecular environments such as the cell cytoplasm.

Who supports? The providers of social support to dual-parent families caring for young children

Previous research points to the importance of both kin and non-kin ties within social networks as sources of social support. This study examines the kin and non-kin providers of specific types of support to dual-parent low-income Australian families caring for young children. The study highlights the importance of family and friends as support providers. Study Participants tended to rely on family, including parents, siblings and other family members, and friends for emotional and information support. Parents also tended to provide material and practical support. While neighbors and community agencies offered some emotional and information support, overall, these sources were minimal. (C) 2002 Wiley Periodicals, Inc.

Use of stress echocardiography to predict mortality in patients with diabetes and known or suspected coronary artery disease

OBJECTIVE - This study sought to determine whether stress echocardiography using exercise (when feasible) or dobutamine echo could be used to predict mortality in patients with diabetes. RESEARCH DESIGN AND METHODS - Stress echo was performed in 937 patients with diabetes (aged 59 +/- 13 years, 529 men) for symptom evaluation (42%) and follow-up of known coronary artery disease (CAD) (58%). Stress echocardiography using exercise was performed in 333 patients able to exercise maximally, and dobutamine echo using a standard dobutamine stress was used in 604 patients. Patients were followed for less than or equal to9 years (mean 3.9 +/- 2.3) for all-cause mortality. RESULTS - Normal studies were obtained in 567 (60%) patients; 29% had resting left ventricular (LV) dysfunction, and 25% had ischemia. Abnormalities were confined to one territory in 183 (20%) patients and to multiple territories in 187 (20%) patients. Death (in 275 [29%] patients) was predicted by referral for pharmacologic stress (hazard ratio [HR] 3.94, P < 0.0001), ischemia (1.77, P <0.0001), age (1.02, P = 0.002), and heart failure (1.54, P = 0.01). The risk of death in patients With a normal scan was 4% per year, and this was associated with age and selection for pharmacologic stress testing. In stepwise models replicating the sequence of clinical evaluation, the predictive power of independent clinical predictors (age, selection for pharmacologic stress, previous infarction, and heart failure; model chi(2) = 104.8) was significantly enhanced by addition of stress echo data (model chi(2) = 122.9). CONCLUSIONS - The results of stress echo are independent predictors of death in diabetic patients with known or suspected CAD.. Ischemia adds risk that is incremental to clinical risks and LV dysfunction.

Use of cyclic variation of integrated backscatter to assess contractile reserve and myocardial viability in chronic ischemic left ventricular dysfunction

The detection of viable myocardium has important implications for management, but use of stress echocardiography to detect this is subjective and requires exposure to dobutamine. We investigated whether cyclic variation (CV) of integrated backscatter (IB) from the apical views could provide a resting study for detection of contractile reserve (CR) and prediction of myocardial viability in 27 patients with chronic ischemic left ventricular (LV) dysfunction. Repeat echocardiography was performed after 6.7 +/- 3.8 months of follow-up; 14 patients underwent revascularization and 13 were treated medically. Using a standardized dobutamine echocardiography (DbE) protocol, images from three apical views were acquired at 80-120 frames/sec at rest and during stress. CR was identified if improvement of wall motion was observed at low dose (5 or 10 mug/kg/min) DbE. Myocardial viability was characterized by improvement at follow-up echocardiography in patients with revascularization. CVIB at rest and low dose dobutamine were assessed in 194 segments with resting asynergy (severe hypokinesis or akinesis), of which 88 (45%) were in patients who underwent revascularization. Of these, CVIB could be measured in 190 (98%) segments at rest and 185 (95%) at low dose dobutamine. Sixty-two (33%) segments had CR during low dose DbE and 50 (57%) segments showed wall-motion recovery (myocardial viability) at follow-up echocardiography. Segments with CR had significantly higher CVIB at rest (P < 0.001) and low dose dobutamine (P = 0.005) than segments without CR. Using optimal thresholds of CVIB (> 8.2 dB) at rest, the accuracy of CVIB for detecting CR was 70%. Compared with nonviable segments, viable segments had significantly higher CVIB at rest (P < 0.001) and low dose dobutamine (P < 0.001). Using optimal thresholds of CVIB (> 5.3 dB) at rest, the accuracy of CVIB for detecting myocardial viability was 85%, which was higher than that in conventional DbE (62%, P < 0.01). Thus, assessment of CV.TB from the apical views is a feasible and accurate tool for detecting CR and predicting myocardial viability in chronic LV dysfunction.

Adjustment of homeless adolescents to a crisis shelter: Application of a stress and coping model

The present study examined the utility of a stress and coping model of adaptation to a homeless shelter among homeless adolescents. Seventy-eight homeless adolescents were interviewed and completed self-administered scales at Time 1 (day of shelter entry) and Time 2 (day of discharge). The mean duration of stay at the shelter was 7.23 days (SD = 7.01). Predictors included appraisal (threat and self-efficacy), coping resources, and coping strategies (productive, nonproductive, and reference to others coping). Adjustment outcomes were Time I measures of global distress, physical health, clinician-and youthworker- rated social adjustment, and externalizing behavior and Time 2 youthworker-rated social adjustment and goal achievement. Results of hierarchical regression analyses indicated that after controlling for the effects of relevant background variables (number of other shelters visited, sexual, emotional, and physical abuse), measures of coping resources, appraisal, and coping strategies evidenced distinct relations with measures of adjustment in ways consistent with the model's predictions with few exceptions. In cross-sectional analyses better Time I adjustment was related to reports of higher levels of coping resources, self-efficacy beliefs, and productive coping strategies, and reports of lower levels of threat appraisal and nonproductive coping strategies. Prospective analyses showed a link between reports of higher levels of reference to others coping strategies and greater goal achievement and, unexpectedly, an association between lower self-efficacy beliefs and better Time 2 youthworker-rated social adjustment. Hence, whereas prospective analyses provide only limited support for the use of a stress and coping model in explaining the adjustment of homeless adolescents to a crisis shelter, cross-sectional findings provide stronger support.

Commonwealth of Australia: July to December 2001

The six-month period from July to December 2001 was an extraordinary phase in Australia’s political history. Until 26 August, when 460 asylum seekers were rescued from their sinking vessel off the Western Australian coast, there was nothing to suggest that politics in Australia would be any different from the usual round of policy pronouncements, routine attacks by the opposition, and the occasional headlinegrabbing scandal. It seemed, as the Australian’s international editor Paul Kelly wrote, that tax would dominate the 2001 federal election campaign (21-22 July 2001). Once the asylum seekers had been rescued by the Norwegian freighter Tampa and refused entry to Australia, however, tax declined in significance. The ramifications of the Tampa incident and its aftermath were still engaging the Australian polity when, on 11 September, terrorists hijacked four passenger jets in the United States and flew two of them into the World Trade Centre in New York, one into the Pentagon, and crashed another in Pennsylvania, killing, it was estimated, more than 6000 people. Both incidents changed Australian politics. The extent and significance of the changes remain to be fully seen, but one short-term effect was to boost significantly the government’s chances of re-election.

Remitting behaviour of Nepalese rural-to-urban migrants: Implications for theory and policy

This article uses data for Nepal to test contemporary hypotheses about the remitting behaviour and associated motives of rural-to-urban migrants and to consider the likely impact of such remittances on rural development. Possibilities for inheritance, degree of family attachment, likelihood of eventual return to place of origin and family investment in the education of the migrants are found to be significant influences on levels of remittances by Nepalese migrants. However, in Nepal, remittances do not seem to result in long-term capital investment in rural areas and so may not promote long-term development of these areas.

Contribution of cholinergic systems to state-dependent modulation of respiratory control

Respiration is altered during different stages of the sleep-wake cycle. We review the contribution of cholinergic systems to this alteration, with particular reference to the role of muscarinic acetylcholine receptors (MAchRs) during rapid eye movement (REM) sleep. Available evidence demonstrates that MAchRs have potent excitatory effects on medullary respiratory neurones and respiratory motoneurones, and are likely to contribute to changes in central chemosensitive drive to the respiratory control system. These effects are likely to be most prominent during REM sleep, when cholinergic brainstem neurones show peak activity levels. It is possible that MAchR dysfunction is involved in sleep-disordered breathing, Such as obstructive sleep apnea. (C) 2002 Elsevier Science B.V. All rights reserved.

Pulse-exposure effects of selected insecticides to juvenile Australian crimson-spotted rainbowfish (Melanotaenia duboulayi)

Laboratory toxicity studies were conducted in southeastern Queensland, Australia, to determine the acute lethal effects of a 1-h pulse exposure of selected insecticides to adult and juvenile (