The interplay of autophagy and ß-Catenin signaling regulates differentiation in acute myeloid leukemia.

The major feature of leukemic cells is an arrest of differentiation accompanied by highly active proliferation. In many subtypes of acute myeloid leukemia, these features are mediated by the aberrant Wnt/ß-Catenin pathway. In our study, we established the lectin LecB as inducer of the differentiation of the acute myeloid leukemia cell line THP-1 and used it for the investigation of the involved processes. During differentiation, functional autophagy and low ß-Catenin levels were essential. Corresponding to this, a high ß-Catenin level stabilized proliferation and inhibited autophagy, resulting in low differentiation ability. Initiated by LecB, ß-Catenin was degraded, autophagy became active and differentiation took place within hours. Remarkably, the reduction of ß-Catenin sensitized THP-1 cells to the autophagy-stimulating mTOR inhibitors. As downmodulation of E-Cadherin was sufficient to significantly reduce LecB-mediated differentiation, we propose E-Cadherin as a crucial interaction partner in this signaling pathway. Upon LecB treatment, E-Cadherin colocalized with ß-Catenin and thereby prevented the induction of ß-Catenin target protein expression and proliferation. That way, our study provides for the first time a link between E-Cadherin, the aberrant Wnt/ß-Catenin signaling, autophagy and differentiation in acute myeloid leukemia. Importantly, LecB was a valuable tool to elucidate the underlying molecular mechanisms of acute myeloid leukemia pathogenesis and may help to identify novel therapy approaches.

The meaning of mobility for residents and staff in long-term care facilities.

BACKGROUND: Although the physical and psychological effects of decreased mobility have been documented, little is known about what it means to be mobile from the institutionalized elders' perspective. Even less is known about nurses' perceptions regarding institutionalized elders' mobility and about mobility enhancing strategies. AIM: The purpose of this study was to generate knowledge about the phenomenon of mobility from both the nurses' and institutionalized elders' perspective. DESIGN: An exploratory qualitative design was used. Focus groups with residents and nursing staff were conducted in three long-term care facilities in a large metropolitan city in 1998. Ethical approval was received from the ethics committees in all three facilities prior to study implementation. Twenty long-term care facility residents and 15 nursing staff participated in the study. METHODS: A trained facilitator used an interview guide to moderate discussions in which residents' and nurses' opinions and feelings about mobility were solicited. The group responses were tape recorded, transcribed and coded. The codes reflected major concepts or abstractions of the data and emerged from the participants' verbal responses to the research questions. FINDINGS: Both groups identified mobility as being pivotal to the residents' quality of life and well-being. The residents viewed mobility as a means of freedom, choice and independence, and they made great efforts to maintain their mobility. The nurses also valued the importance of mobility and assisted the residents through preparatory care, environmental modifications and encouragement. Factors that related to the residents' willingness to be mobile, environmental barriers and the impact of waiting were compared between the two groups. CONCLUSION: Mobility involves more than the movement from one point to another. The nature of the assistive nurse-client relationship and the resident's subjective perspective must become central to understanding the meaning of mobility for residents in a long-term care facility.

Modulation of growth factor binding properties of alpha2-macroglobulin by enzyme therapy.

PURPOSE: To investigate the binding of transforming growth factor-beta (TGF-beta) to human alpha2-macroglobulin upon oral treatment of patients with proteases. METHODS: Volunteers were given a cocktail of active proteinases (Phlogenzym) composed of trypsin, bromelain and the additive rutoside orally over a period of 7 days at low dose followed by a bolus application. Before and after medication plasma was immediately withdrawn and binding of 125I-TGF-beta to the proteinase inhibitor alpha2-macroglobulin was determined by electrophoresis and gamma-counting. Cell culture experiments were performed to study the effect of transformed alpha2-macroglobulin on TGF-beta-stimulated proliferation of skin fibroblasts. RESULTS: Ingestion of proteinases was found to trigger the formation of intermediate forms of alpha2-macroglobulin displaying high affinity to TGF-beta. Maximum binding of TGF-beta was observed 1-2 h after bolus ingestion, and steadily levelled off with time. In vitro experiments demonstrated that complex formation of diverse proteinases (trypsin, alpha-chymotrypsin, bromelain and plasmin) with alpha2-macroglobulin conferred binding of 125I-TGF-beta, alpha2-Macroglobulin transformed by methylamine or proteinases was found to abolish the TGF-beta effect on fibroblasts in cell culture. CONCLUSIONS: Intestinal absorption of proteinases triggers the formation of TGF-beta binding species of alpha2-macroglobulin in blood. Mediated by this process high concentrations of TGF-beta might be reduced via enhanced clearance of alpha2-macroglobulin-TGF-beta complexes. Thus, proteinase therapy may have beneficial effects in treatment of fibrosis and certain cancers accompanied by excessively high TGF-beta concentrations.

Adaptation to chronic illness and disability and its relationship to perceptions of independence and dependence.

This study extends research on living with chronic physical illness and disability by examining how adaptation processes are associated with different activity domains and how the combination of adaptations and activity domains relate to older adults' perceptions of their independence and dependence, helplessness, emotional reactivity, and coping efficacy. The study investigated the behavioral efforts that 286 older adults with osteoarthritis and/or osteoporosis used to adapt to disability arising from their condition. The findings revealed that adults used a wide range of adaptations, including compensations for loss, optimizing performance, limiting or restricting activities, and gaining help from others. The relative use of each of these adaptations varied across 5 domains of activity: personal care, in-home mobility, community mobility, household activities, and valued activities. Moreover, older adults' perceptions of their independence, dependence, helplessness, emotional reactivity, and coping efficacy varied depending on the domain of activity examined and the type of adaptation used.

Determinants of self rated health for Canadians with chronic disease and disability.

OBJECTIVE: To identify the factors associated with self rated health of people with and without chronic health conditions or long term disability. SETTING: Canadian household population. DESIGN: Analysis of 1994/95 National Population Health Survey interview data with 13,995 respondents aged 20 years and older. Determinants of poor and good compared with excellent health were examined using multivariate nominal logistic regression. Factors included in the analyses were illness related (chronic disease, long and short-term disability, and pain) demographic, lifestyle (smoking, physical activity, drinking), and social psychological resources (mastery, chronic stress, distress, self esteem, and social support). RESULTS: Illness related variables were associated with poor health, with smaller but significant contributions from demographic and lifestyle factors. Psychological resources, especially high mastery and self esteem, are associated with better health in those with chronic conditions or disability. CONCLUSION: The determinants of self rated health for people with chronic illness and disability make the greatest contribution to the findings for the overall population.

A conceptual model of independence and dependence for adults with chronic physical illness and disability.

This paper presents a conceptual model of physical independence and dependence as it relates to adult onset, chronic physical illness and disability. Physical independence and dependence are presented as two separate, continuous, and multiply determined constructs, and illustrations are provided of situations where people can be independent, dependent, not independent, or experience imposed dependence. The paper also discusses potential determinants of physical independence and dependence, including different domains of disability, the role of subjective perceptions, demographics, the physical and social/political environments, personal resources, attitudes and coping resources, illness and efficacy appraisals, and the nature of the assistive relationship. The paper extends work on physical independence and dependence by synthesizing the findings from previous studies and incorporating the findings from other relevant areas of research into the area. It also expands on the concepts of physical independence and dependence, as well as their determinants, and relates independence and dependence to other outcomes of interest such as service delivery.

"We decide, you carry it out": a social network analysis of multidisciplinary long-term care teams.

The purpose of this study was to describe the structure of multidisciplinary long-term care teams by identifying the pattern of relationships that develop amongst staff as they go about their work. Using a social network analysis approach, team members were classified as occupying the same structural position based on their patterns of relationships with other team members. The analysis was based on the results of a self-administered survey of 93 health care workers on three teams in the same multilevel geriatric care facility in Metropolitan Toronto. A common structure of the teams was identified consisting of two sub-teams: a multiprofessional sub-team and a nursing sub-team, each of which has a different structure indicating differential involvement in different types of teamwork. The multiprofessional sub-team has an "organic" structure and is mainly involved in teamwork that involves decision-making and problem-solving, whereas the nursing sub-team has a "mechanistic" structure and is mainly involved in task oriented work. The findings of this analysis indicate that while teamwork may be increasing the participation in decision-making by health professionals other than medicine, rather than flattening the hierarchical structure throughout the health care division of labour, its effects are limited to a group of higher status professionals. The clearly defined hierarchy remains for the lower status subdisciplines, and "I decide, you carry it out" has simply become "We decide, you carry it out".

New radio service targets EMS communications.

The EMS community should commend the FCC for attempting to help relieve some of the frequency-congestion problems by adopting the EMRS. EMS users, however, should continue to advocate cost-effective solutions to EMS frequency-congestion problems.

Goal-setting in physical therapy practice.

Goal-setting is traditionally used by physical therapists; however, factors identified in the literature as increasing goal achievement are often not considered. The purpose of this paper is to describe the potential use of goal-setting in improving and measuring effectiveness in physical therapy practice. Factors identified in the literature for effective goal-setting include setting specific and measurable goals, degree of goal difficulty, goal acceptance, and feedback. Active participation by the client in the goal-setting process is of primary importance. In order to maximize the use of goal-setting in physical therapy practice, reliable, valid, and sensitive clinical measures need to be identified and developed. There appears to be a potential for further use of goal-setting in physical therapy practice both as a means of improving treatment effectiveness and as a method for measuring effectiveness of treatment programs.