ADAMTS-4 activity on a proteoglycan vs. a polypeptide is controlled by the ancillary domains

Introduction In combination with the catalytic domain, the ancillary domains of the ADAMTS' are proposed to regulate activity via interactions with sulfated GAGs, the extracellular matrix (ECM) and cell surface. Interactions with both GAGs and the ECM have been attributed to the thrombospondin (TSP) type 1 motifs and spacer region ( Kuno and Matsushima 1998 ; Flannery et al. 2002 ). ADAMTS‐1, ‐4 and ‐5, all undergo cleavage within their respective spacer regions ( Flannery et al. 2002 ; Rodriguez‐Manzaneque et al. 2000 ; Georgiadis et al. 2002 ), an event which has been reported to increase activity towards the interglobular domain of aggrecan and decrease the heparin affinity of ADAMTS‐4 ( Flannery et al. 2002 ; Gao et al. 2002 ). Materials and methods V5‐ and His‐tagged recombinant human ADAMTS‐4 constructs terminating after the catalytic (?DTS), disintegrin‐like (?TS), TSP (?S) or spacer region (Full) were expressed in High‐Five cells. Proteoglycanase activities of the resultant proteins were assayed with solution digests of aggrecan and a polyacrylamide‐entrapped aggrecan particle assay. Proteolytic activity was measured using a novel, nonglycosylated, reporter substrate assay. Results All forms of ADAMTS‐4 were active to varying degrees in the reporter substrate assay. Digestion of aggrecan in solution digests was apparent in all proteins with the exception of the catalytic domain in isolation (?DTS). Activity towards aggrecan decreased with increasing truncation of the protein. Discussion Removal of the cysteine‐rich‐spacer domain and further C‐terminal truncations decrease the activity of ADAMTS‐4 towards aggrecan, whilst the proteolytic activity remains intact. Cleavages releasing the ancillary domains of ADAMTS' may therefore alter the catalytic activity of these enzymes against proteoglycans and also nonglycosylated polypeptides. More information is required about potential substrates for the processed forms of ADAMTS‐4.     

Cardiac rehabilitation for women: one size does not fit all.

AIM: To investigate women's perceptions of the contribution of cardiac rehabilitation to their recovery from a myocardial infarction. BACKGROUND AND PURPOSE: Cardiac rehabilitation programs have been based on research with almost exclusively male participants. It was unclear if cardiac rehabilitation programs meet the needs of women. METHOD: Ten women who had experienced one or more myocardial infarctions were interviewed. Data from these interviews were analysed using Glaserian grounded theory. FINDINGS: The core category that emerged from the data was 'regaining everydayness'. Participants worked to regain their 'everydayness' through a basic social process of 'reframing'. Reframing involved coming to terms with what they had experienced and fitting it into their lives. Other categories related to symptom recognition and recovery. CONCLUSION: Cardiac rehabilitation programs contributed to overall recovery from a myocardial infarction in different ways for each participant. Although programs provided information for participants, they failed to provide the type of support needed to effectively aid reframing and recovery. Programs did not meet the needs of all participants and it was apparent that one size does not fit all.     

Exercise and older adults

The benefits of regular physical activity in older persons are numerous and well established. Regular physical activity in older adults is associated with an overall improvement in health, functional capacity, quality of life, and independence. Many questions arise for healthcare providers regarding an older person’s ability and motivation to be physically active. The healthcare provider has a unique opportunity to assess the older client’s incentives, preferences, and abilities for physical activities, as well as to prescribe a safe, appropriate, and enjoyable exercise plan. The exercise precription can be simple yet thorough enough to ensure benefits in an older person’s health and functional capacity.     

Characteristics of apathy in Parkinson's disease.

The objective of this study was to use the Lille Apathy Rating Scale to assess apathy in a large population of Parkinson's disease (PD) patients and identify several different apathy profiles. One hundred fifty-nine patients with probable PD and 58 healthy controls participated in the study. Apathy was assessed using the Lille Apathy Rating Scale. Motor, cognitive, and depressive symptoms were rated on standardized scales. Data were analyzed using linear regression and multivariate analyses of variance. Thirty-two percent of the PD patients were classified as apathetic. Apathy was more frequent in patients with dementia. The four apathy dimensions contributed differently to the overall severity of the apathetic condition. Action initiation and intellectual curiosity had a marked influence. Linear regression analysis revealed that the apathy level was mainly determined by cognitive impairment, not associated with the severity of motor symptoms, and only associated with the apathy subcomponent of the Montgomery and Asberg Depression Rating Scale. Apathy is highly prevalent in PD patients. Apathy profiles vary according to the clinical presentation of PD. The high prevalence of apathy in PD suggests the involvement of frontal-subcortical circuits. Although the neurochemical substrate of apathy remains poorly characterized, the strong link between apathy and cognitive impairment observed in several studies suggests the participation of nondopaminergic circuits.     

Cutting edge technology to enhance nursing classroom instruction at Coppin State University.

Educational technologies have changed the paradigm of the teacher-student relationship in nursing education. Nursing students expect to use and to learn from cutting edge technology during their academic careers. Varied technology, from specified software programs (Tegrity and Blackboard) to the use of the Internet as a research medium, can enhance student learning. The authors provide an overview of current cutting edge technologies in nursing classroom instruction and its impact on future nursing practice.     

Laparoscopic cholecystectomy in a patient with a biventricular cardiac assist device.

Evaluation and management of abdominal pathology in patients with ventricular assist devices is likely to become increasingly important as the utilization of these devices expands. Ventricular assist devices represent a class of intracorporeal or paracorporeal mechanical devices that augment cardiac output in patients with congestive heart failure. Patients with ventricular assist devices supporting both right and left ventricles (biventricular assist devices) are uniquely challenging to the general surgeon because these devices restrict direct access to the abdominal cavity and because of the perioperative implications of biventricular heart failure. We describe herein the first reported successful laparoscopic cholecystectomy in a patient with a paracorporeal biventricular assist device. Cholecystectomy was performed in this patient for acute cholecystitis that occurred while the patient was awaiting heart transplantation. Our results add weight to the small body of evidence that laparoscopy is well tolerated in ventricular assist devices patients. The unique aspects of the biventricular assist device patient make laparoscopic abdominal intervention particularly suitable in this patient population.     

Principle-based ethics and nurses' attitudes towards artificial feeding

Nurses often institute artificial feeding for patients who would otherwise starve Recently, the courts in the United States have favoured withholding or withdrawing feedings from patients who currently refuse or previously gave some indication they would refuse artificial nutrition and hydration This paper investigates under what circumstances nurses feel justified in withholding artificial nutrition and hydration Structured interviews were conducted with 40 cancer care nurses from two sites, and 40 dementia care nurses from two sites The interviews were based on two vignettes, one involving an alert patient with terminal cancer, the other a patient suffering end-stage Alzheimer's dementia, and were analysed for themes coinciding with principles of deontological ethics Investigators found that autonomy, beneficence and non-maleficence most often guided nurses' decisions to withhold or implement artificial feeding     

A survey of household food purchases and dietary habits in relation to affluence among Singapore Chinese

A survey of 40 Singapore Chinese households was performed, obtaining information on major perishable foods purchased for home consumption in the previous week, extent of home consumption (eating in), household dietary habits and housing type, the last as a measure of affluence. Eating out was very common: nine (23 per cent) households ate less than 50 per cent of meals at home. Excluding these nine households, consumption and habits were compared between more affluent and less affluent households. The more affluent households purchased more red meat/offal (P = 0.001), poultry (P = 0.002), vegetables other than green leafy (P = 0.04), fruit (P = 0.007) and eggs (P = 0.04); they also differed significantly in various dietary habits. Significant differences were also observed between English-speaking and Chinese-speaking households. The results suggest that increasing affluence may have brought about substantial dietary change in Singapore, thus meriting further study of the role of diet in changing disease patterns in Singapore.     

Cocaine-induced Increase in Cortical Acetylcholine Release: Interaction with the Hypothalamo—Pituitary—Adrenal Axis

An influence on drug-taking behaviours of the stress-related hypothalamo-pituitary-adrenal (HPA) axis and its final hormonal mediator, corticosterone, has previously been demonstrated. A role for cortically projecting cholinergic neurons in these behaviours can also be proposed. The experiments presented here examine the effect of the drug of abuse cocaine (15 mg/kg) on the release of acetylcholine (ACh) in the cortex of freely moving rats, using the technique of in vivo microdialysis. To assess a possible modulatory influence of the HPA axis via its final hormonal mediator corticosterone, the cocaine-induced effect on cortical ACh release in intact rats was compared to that in adrenalectomized (ADX) rats, which thus lacked their endogenous source of corticosterone, and in ADX rats in which the cocaine-induced corticosterone peak and/or the basal circadian concentrations of serum corticosterone were simulated by replacement treatments. The results reported here demonstrate that cortical ACh release is greatly increased by cocaine in intact rats; ADX prolongs the return to basal levels of cortical ACh, and the chronic replacement of circadian levels of corticosterone normalizes this effect. In contrast, during the plateau period of cocaine-induced increased cortical ACh release, where no effect of ADX is evident, rats with chronic replacement of corticosterone show an attenuated cocaine-induced cortical ACh release, and the acute replacement of the cocaine-induced corticosterone secretion further attenuates this response. These results demonstrate that cocaine stimulates cortically projecting cholinergic neurons, and that the HPA hormone corticosterone modulates this interaction in a complex manner which merits further investigation.