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PubMed1991

Activation of programmed cell death by recombinant human tumor necrosis factor plus topoisomerase II-targeted drugs in L929 tumor cells.

The mechanism of death induced by recombinant human tumor necrosis factor (rHuTNF) in L929 tumor cells of C3H mice was investigated. Treatment with rHuTNF led to fragmentation of DNA into nucleosomal oligomers and to induction of the expression of TRPM-2, a programmed cell death-associated gene. Both events preceded cell death by several hours. Treatment with DNA topoisomerase II inhibitors accelerated both the rHuTNF-mediated DNA fragmentation and the elevation in TRPM-2 messenger RNA levels. These results suggest that rHuTNF exerts its cytotoxicity on L929 cells by activating programmed cell death, leading to apoptosis, and that topoisomerase II inhibitors enhance rHuTNF-mediated cytotoxicity by accelerating this process.

Animals↗

PubMed1997

Programs and services to prevent pregnancy, childbearing, and poor birth outcomes among adolescents in rural areas of the southeastern United States.

PURPOSE: To illustrate how rural adolescents' needs for pregnancy prevention and improved birth outcomes are currently being addressed, and to suggest strategies for future programs. METHODS: Local and state-level informants knowledgeable about services to adolescents in the Southeastern United States were identified. Semistructured interviews were used to determine the program start date and time frame, funding sources, target population, participating counties, implementing agency or organization, specific program services, and status of program activities. These programs were categorized by the type of services offered and the population targeted. RESULTS: The most common adolescent services in the rural Southeast attempt either to improve life options of youth, reduce sexual activity, or provide prenatal and postnatal care. Unlike urban areas where there are a variety of family planning providers, in the rural Southeast, health departments are the primary source of family planning for adolescents. There are no abortion providers in most rural areas of the Southeast. The majority of rural programs that include adolescents among the population served are developed for all women rather than specifically for adolescents. Programs specific to rural adolescents are described. CONCLUSIONS: The majority of programs in the rural Southeast address only selected adolescent health issues. Successful interventions require locally supported, multipronged, intensive approaches with consistent messages targeted to high-risk populations. Evaluation tools are needed to determine the effectiveness of each component of prevention programs.

Adolescent↗

PubMed1995

FK506 augments activation-induced programmed cell death of T lymphocytes in vivo.

FK506 is an immunosuppressive drug that inhibits T cell receptor-mediated signal transduction. This drug can induce immunological tolerance in allograft recipients. In this study, we investigated the in vivo effects of FK506 on T cell receptor-mediated apoptosis induction. Injection of anti-CD3 antibody (Ab) in mice resulted in the elimination of CD4+ CD8+ thymocytes by DNA fragmentation. FK506 treatment significantly augmented thymic apoptosis induced by in vivo anti-CD3 Ab administration. Increased thymic apoptosis resulted in the disappearance of CD4+ CD8+ thymocytes after anti-CD3 Ab/FK506 treatment. DNA fragmentation triggered by FK506 was induced exclusively in antigen-stimulated T cells, since enhanced DNA fragmentation induced by in vivo staphylococcal enterotoxin B (SEB) injection was confirmed in SEB-reactive V beta 8+ thymocytes but not in SEB-nonreactive V beta 6+ thymocytes. In addition to thymocytes, mature peripheral T cells also die by activation-induced programmed cell death. A similar effect of FK506 on activation-induced programmed cell death was observed in SEB-activated peripheral spleen T cells. In contrast, cyclosporin A treatment did not enhance activation-induced programmed cell death of thymocytes and peripheral T cells. Apoptosis is required for the generation and maintenance of self-tolerance in the immune system. Our findings suggest that FK506-triggered apoptosis after elimination of antigen-activated T cells may represent a potential mechanism of the immunological tolerance achieved by FK506 treatment.

Animals↗

PubMed2002

Crk synergizes with epidermal growth factor for epithelial invasion and morphogenesis and is required for the met morphogenic program.

Activation of the Met receptor tyrosine kinase through its ligand, hepatocyte growth factor, stimulates cell spreading, cell dispersal, and the inherent morphogenic program of various epithelial cell lines. Although both hepatocyte growth factor and epidermal growth factor (EGF) can activate downstream signaling pathways in Madin-Darby canine kidney epithelial cells, EGF fails to promote the breakdown of cell-cell junctional complexes and initiate an invasive morphogenic program. We have undertaken a strategy to identify signals that synergize with EGF in this process. We provide evidence that the overexpression of the CrkII adapter protein complements EGF-stimulated pathways to induce cell dispersal in two-dimensional cultures and cell invasion and branching morphogenesis in three-dimensional collagen gels. This finding correlates with the ability of CrkII to promote the breakdown of adherens junctions in stable cell lines and the ability of EGF to stimulate enhanced Rac activity in cells overexpressing CrkII. We have previously shown that the Gab1-docking protein is required for branching morphogenesis downstream of the Met receptor. Consistent with a role for CrkII in promoting EGF-dependent branching morphogenesis, the binding of Gab1 to CrkII is required for the branching morphogenic program downstream of Met. Together, our data support a role for the CrkII adapter protein in epithelial invasion and morphogenesis and underscores the importance of considering the synergistic actions of signaling pathways in cancer progression.

Animals↗

PubMed2000

Signaling pathways engaged by NK cell receptors: double concerto for activating receptors, inhibitory receptors and NK cells.

Despite the absence of antigen-specific receptors at their surface, NK cells can selectively eliminate virus-infected cells, tumor cells and allogenic cells. A dynamic and precisely coordinated balance between activating and inhibitory receptors governs NK cell activation programs. Multiple activating and inhibitory NK cell surface molecules have been described, a group of them acting as receptors for MHC class I molecules. In spite of their heterogeneity, activating NK cell receptors present remarkable structural and functional homologies with T cell- and B cell-antigen receptors. Inhibitory NK cell receptors operate at early stages of activating cascades by recruiting protein tyrosine phosphatases via intra- cytoplasmic motifs (ITIM), a strategy which is widely conserved in hematopoietic and non-hematopoietic cells.

Cytotoxicity, Immunologic↗

PubMed1975

Challenging residents to assume maximal responsibilities in homes for the aged.

A program for activating residents of homes for the aged to assume maximal responsibilities is described. Promoting maximal physical and mental health through various modalities including activity programs, appropriate exercise and participation in democratic self-government mechanisms, will result in a happier, healthier population of residents in institutions for the aged. The increased demands on staff time and patience will be compensated for by relief of the too-frequent feelings of hopelessness and boredom endemic among the staff of long-term care facilities. Such programs demand constant effort by all staff members, patients, volunteers and relatives because if they succumb to the usual human dislike of persistency, short-term gains can easily be lost.

Aged↗

PubMed1986

Outcome for court-referred drug-abusing male adolescents of an alternative activity treatment program in a vocational high school setting.

This is a report of outcome of an alternative activity treatment program, consisting of off-campus supportive life skill activities, in a private vocational high school for court-adjudicated delinquent boys. A total of 130 adolescent male drug abusing student-clients were evaluated at follow-up, 22 months after admission to the day school treatment program. The determination of graduation vs. dropping out was made 3 years after admission to the study. The sample was 75% white, 21% black, and 4% Hispanic. Eighty-two percent were from 16 to 18 years of age, but only 24% had completed the 10th grade. The mean number of different types of drugs "ever used" was 5.87, and the mean number of drug sale offenses was 4.4. Sixty-one percent had been incarcerated (overnight or longer). A comprehensive assessment was administered at admission and at follow-up. The findings developed by paired t-test, comparing the student-clients' self-reports at follow-up evaluation with their self-reports at pretreatment, indicated significant improvement in numerous problem areas of behavior, adjustment, and attitude measured, except that no significant reduction in illicit drug use occurred. The improvement, however, was more related to the vocational training and job placement program and the general milieu of the school than to the off-campus supportive life skills program. The latter was shown to have a highly significant positive association with outcome as measured by success in graduating from high school and a significant positive association to improvement in "personal adjustment" (reduction in personal problems and increase in interpersonal maturity).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1995

Active treatment programs for patients with chronic low back pain: a prospective, randomized, observer-blinded study.

Several new studies have indicated that an active approach to patients with chronic disabling low back pain (LBP) seems effective. Some of these studies emphasize the importance of dealing with the patient's total situation in comprehensive multidisciplinary programs--the bio-psycho-social model. However, these programs are expensive. The aim of this study was to evaluate the rehabilitation outcome from three different active programs in terms of: (1) return-to-work rate, (2) days of sick leave, (3) health-care contacts, (4) pain and disability scores, and (5) staying physically active. The subjects included 132 patients randomized to the study, of whom 123 started one of the treatment programs. They had all had at least 6 months of chronic LBP. The patients were randomized into one of three programs: group 1--a full-time, intensive 3-week multidisciplinary program, including active physical and ergonomic training and psychological pain management, followed by 1 day weekly for the subsequent 3 weeks; group 2--active physical training, twice a week for 6 weeks, for a total of 24h; group 3--psychological pain management combined with active physical training, twice a week for 6 weeks, also for a total of 24h. The results presented here are based on data collected 4 months following treatment, which shows an 86% response rate. The initial examination and the follow-up evaluation were performed by a blinded observer. The results show that 4 months after treatment, the intensive multidisciplinary program is superior to the less intensive programs in terms of return-to-work rate, health-care contacts, pain and disability scores, and staying physically active.(ABSTRACT TRUNCATED AT 250 WORDS)

Absenteeism↗

PubMed1981

The GENE-TOX program: genetic activity evaluation.

The GENE-TOX program, a two-phase evaluation from the existing literature of selected bioassays for detecting mutagenicity and presumptive carcinogenicity, is described. Sponsored and directed by the Office of Testing and Evaluation within the U.S. Environmental Protection Agency's (EPA) Office of Pesticides and Toxic Substances, this program will aid EPA in establishing standard genetic testing and evaluation procedures for the regulation of toxic substances and determining the direction of research and development in the area of genetic toxicology.

Animals↗

PubMed1999

Association of obesity with physical activity, television programs and other forms of video viewing among children in Mexico city.

OBJECTIVE: To assess the association of physical activity, television program viewing and other forms of video viewing with the prevalence of obesity among school children. DESIGN: Cross-sectional study. SUBJECTS: 712 children, 9-16 y old, from a low- and a middle-income town in the Mexico City area. MEASUREMENTS: Children completed a self administered questionnaire to assess time spent in physical activity and television viewing, and diet. Height weight and triceps skinfolds were measured. The outcome variable was obesity, and the covariates were hours of television programs and other video viewing, physical activity, energy intake, percentage of energy from fat, town of location of school, age, gender and perception of mother's weight status. RESULTS: Among 461 children with complete information, 24% were classified as obese. Children reported an average of 4.1 +/- 2.2 h/d watching television (2.4 +/- 1.5 h/d for TV programs and 1.7 +/- 1.5 h/d for video cassette recorder (VCR) or videogames), and 1.8 +/- 1.3 h/d in moderate and vigorous physical activities. Odds ratios (OR) of obesity were 12% higher for each hour of television program viewing per day (OR = 1.12, 95% confidence interval (CI) 1.02,-1.22), and 10% lower for each hour of moderate/vigorous physical activity per day (OR = 0.90, 95% CI 0.83-0.98), controlling for age, gender, town and perception of mother's weight status. Children in the middle-income town had higher adjusted odds of obesity (OR = 2.58, 95% CI 1.47-4.54). CONCLUSION: Physical activity and television viewing, but not VCR/videogames use, were related to obesity prevalence in Mexican children 9-16 y old.

Adolescent↗

PubMed1995

Does physical activity improve sleep in impaired nursing home residents?

OBJECTIVES: To determine if two physical activity programs of varying intensity would result in improved sleep among incontinent and physically restrained nursing home residents. DESIGN: Controlled trials of two physical activity programs. SETTING: Seven community nursing homes in the Los Angeles area. PARTICIPANTS: Residents were included if they had urinary incontinence or were physically restrained. Sixty-five subjects were studied. Mean age was 84.8 years, 85% were female, mean length of residency in the nursing home was 19.9 months, and mean Mean Mini-Mental State Exam score was 13.1. INTERVENTION: The first physical activity program involved sit-to-stand repetitions and/or transferring and walking or wheelchair propulsion. These activities were performed every 2 hours during the daytime, 5 days per week for 9 weeks. The second, less frequent physical activity program involved rowing in a wheelchair-accessible rowing machine plus walking or wheelchair propulsion once per day three times per week for 9 weeks. MEASUREMENTS: The physical function measures reported here include mobility endurance (maximum time walking or wheeling) and physical activity as measured by motion sensors (Caltrac). Nighttime sleep was estimated by wrist activity monitors. Nighttime sleep measures included total time asleep, percent sleep, average duration of sleep, and peak duration of sleep. Daytime sleep was measured by timed behavioral observations of sleep versus wakefulness performed every 15 minutes during the day. RESULTS: Nighttime sleep was markedly disrupted in both groups at baseline. Across all subjects at baseline, the average total sleep time was 6.2 hours and the percent sleep was 72.0%, but the average duration of sleep episodes was only 21.2 minutes and the peak duration of sleep episode averaged only 83.8 minutes. During the daytime, subjects were observed asleep during 14.5% of observations. Although there was improvement in mobility endurance in the intervention subjects compared with controls (MANOVA F = 4.36, P = .042), there were no differences in the night and day sleep measures at follow-up testing. Even among a subgroup of intervention subjects who showed a 30% or greater improvement in mobility endurance, sleep did not improve at follow-up compared with baseline. CONCLUSION: This study supports our previous findings of marked sleep disruption in impaired nursing home residents. In addition, despite documented improvements in physical function with activity, we did not find improvements in sleep in the intervention versus control groups. These results suggest that increasing daytime physical activity alone is not adequate to improve sleep in impaired NH residents. Future efforts to improve sleep in this population should take into account the multifactorial nature of sleep disruption, including individual health problems that effect sleep and the disruptive nature of the nighttime NH environment.

Aged↗

PubMed2000

Differences in psychosocial determinants of physical activity in older adults participating in organised versus non-organised activities.

BACKGROUND: With the introduction of the new consensus on 30 minutes of moderate physical activity preferably on all days of the week, exercise implemented into daily activities is promoted whereas structured activity programs lose importance. Activity levels of most older people don't come up with current recommendations. Therefore strategies to enhance attendance of older adults in physical activities should be developed. Group programs may be more effective in changing exercise behaviour of older adults than non-supervised physical activity. The purpose of this study was to investigate the differences in level of activity and psychosocial determinants of physical activity between seniors involved in an exercise class and seniors not engaged in any organised physical activity. METHODS: Seventy-five elderly who were currently involved in structured exercise classes and 75 elderly who did not participate in any organised physical activity during the previous year were recruited in senior citizens' centres and were asked to fill out a questionnaire. RESULTS: Subjects involved in an exercise program had higher levels of activity and reported more social influences and higher self-efficacy compared to the respondents practising on an individual basis. No differences were found in perceived barriers or benefits. CONCLUSIONS: Exercising in a group program gives the opportunity to accumulate some extra physical activity and positively affects the level of activity outside the program. Stimulating older adults to join a structured activity program in the company of family or friends in order to enhance supporting social influences and perceived competence could be an important intervention strategy.

Aged↗

PubMed1976

Physical activities: teaming up patients and programs.

Physical activities programs are suggested for the average deconditioned individual over 35 years of age. They involve noncontact, noncompetitive aerobic activities which require minimal expense. Their purpose is to delay to some degree the progression of the degenerative diseases associated with aging and inactivity. The best activities are walking, running, bicycling, or other exercise in which a sustained cardiac rate of 70% of the individual's work capacity is achieved.

Adult↗

PubMed1997

Bcl-x(L) can inhibit apoptosis in cells that have undergone Fas-induced protease activation.

Programmed cell death or apoptosis provides an irreversible mechanism for the elimination of excess or damaged cells. Several recent studies have implicated the activation of the interleukin 1beta-converting enzyme/Ced-3 (ICE/Ced-3) family of proteases as the "point of no return" in apoptotic cell death, while others have suggested that loss of mitochondrial membrane potential (delta psi(m)) is the ultimate determinant of cell death. The temporal relationship of these two events during apoptosis and the role of Bcl-2 proteins in inhibiting these steps has not been defined. To examine these issues, control and Bcl-x(L)-transfected Jurkat T cells were treated with Fas antibodies in the presence and absence of the ICE protease inhibitor zVAD-FMK. ICE/Ced-3 protease activity was monitored by following the cleavage of poly(ADP-ribose) polymerase (PARP) and delta psi(m) was followed by rhodamine 123 fluorescence. Although Bcl-x(L) expression did not block Fas-induced protease activation, it substantially inhibited the subsequent loss of delta psi(m) and cell death in Fas-treated cells. In contrast, zVAD-FMK blocked PARP cleavage as well as loss of delta psi(m) and cell death. Together these data demonstrate that Bcl-x(L) can maintain cell viability by preventing the loss of mitochondrial membrane potential that occurs as a consequence of ICE/Ced-3 protease activation.

Apoptosis↗

PubMed1999

A framework for the evaluation of activities and programs with harm-reduction objectives.

This paper presents a framework for the evaluation of activities and programs with harm-reduction objectives that draws attention to the logic, implementation, outcomes, costs, and cost-effectiveness of these initiatives and encompasses stakeholder concerns and theoretical models. Evaluations of harm-reduction initiatives are essential if their proponents wish to establish them as viable alternatives to abstinence-oriented approaches. [Translations are provided in the International Abstracts Section of this issue.]

Canada↗

PubMed2002

A brief intervention for hazardous drinkers in a needle exchange program.

Active injection drug users (IDUs) who are also hazardous alcohol users are at particularly high risk for HIV transmission due to sharing of injection equipment. We recruited AUDIT-positive injectors from the Providence, RI needle exchange program for a randomized clinical trial testing the effect of a brief motivational intervention (MI) on frequency of injection-related HIV risk behavior (IRRB). HIV drug risk behavior was measured as the number of days on which subjects reported sharing works using the 30-day Timeline Followback Method. Overall, 109 subjects reported a mean reduction of IRRB days of 9.1 days from baseline to 6-month follow-up (p <.001). When compared to controls, there was a trend in reduction of IRRB days to zero at follow-up for MI subject (OR = 2.1; 95% CI = 0.9-4.5), and strongly significant reductions in IRRB days across a range of alternative improvement thresholds. Results from this study demonstrate that MI reduces drug-related HIV risk behaviors among active IDUs. As a brief intervention, MI may be a useful adjunct to existing services intended to reduce harm.

Adult↗

PubMed2001

Physicians Taking Action Against Smoking: an intervention program to optimize smoking cessation counselling by Montreal general practitioners.

In 1997 the Direction de la santé publique de Montréal-Centre initiated "Physicians Taking Action Against Smoking," a 5-year intervention program to improve the smoking cessation counselling practices of general practitioners (GPs) in Montreal. Program development was guided by the precede-proceed model. This model advocates identifying factors influencing the outcome, in this case counselling practices. These factors are then used to determine the program objectives, to develop and tailor program activities and to design the evaluation. Program activities during the first 3 years included cessation counselling workshops and conferences for GPs, publication of articles in professional interest journals, publication of clinical guidelines for smoking cessation counselling and dissemination of educational material for both GPs and smokers. The program also supported activities encouraging smokers to ask their GPs to help them stop smoking. Results from 2 cross-sectional surveys, conducted in 1998 and 2000, of random samples of approximately 300 GPs suggest some improvements over time in several counselling practices, including offering counselling to more patients and discussing setting a quit date. More improvements were observed among female than male GPs in both psychosocial factors related to counselling and specific counselling practices. For example, improvements were noted among female GPs in self-perceived ability to provide effective counselling and in the belief that it is important to schedule specific appointments to help patients quit; in addition, the perceived importance of several barriers to counselling decreased among female GPs. A greater proportion of the female respondents to the 2000 survey offered written educational material than was the case in 1998, and a greater proportion of the male GPs devoted more time to counselling in 2000 than in 1998; however, among male GPs the proportion who discussed the pros and cons of smoking with patients in the pre-contemplation stage declined between 1998 and 2000, as did the proportion who referred patients in the preparation stage to community resources. Our experience suggests that an integrated, theory-based program to improve physicians' counselling practices could be a key component of a comprehensive strategy to reduce tobacco use.

Counseling↗

PubMed1999

Longitudinal study of calcium intake, physical activity, and bone mineral content in infants 6-18 months of age.

Although increased physical activity early in life is recommended for optimizing bone health, no controlled trials on the effect of activity on bone mass accretion during periods of rapid growth have been reported. The purpose of this study was to determine whether infants randomized to a 1 year gross motor activity program had a greater bone mass accretion than infants randomized to a fine motor activity program. The gross motor program included activities that focused on loading the skeleton and were performed for 15-20 minutes/day, 5 days/week by study personnel. Infants (n = 72) were enrolled at 6 months of age, and total body bone mineral content (BMC), 3-day diet records, and activity levels were obtained at 6, 9, 12, 15, and 18 months. BMC was associated with weight, length, and bone area at all ages and correlated with earlier calcium intakes. Calcium intake appeared to modify the effect of gross motor activity on bone mass accretion; infants in both groups had similar bone accretion at moderately high calcium intakes, but at low calcium intakes infants in the gross motor program had less bone accretion than infants in the fine motor program. Compliant infants in the gross motor group had lower BMC at 18 months compared with noncompliant infants. These results indicate that BMC in infants is related to calcium intake, and we speculate that participation in a gross motor program during rapid bone growth may lead to reduced bone accretion in the presence of a moderate to moderately low calcium intake.

Bone Density↗