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PubMed1995

Induction of apoptosis in catecholaminergic PC12 cells by L-DOPA. Implications for the treatment of Parkinson's disease.

The hypothesis that L-DOPA therapy in Parkinson's disease may augment neuronal damage and thus accelerate the progression of the disease remains controversial. In this study, we demonstrate that L-DOPA induces death of catecholaminergic cells in vitro via an active program of apoptosis. Treatment of PC12 cells with clinically applicable concentrations of L-DOPA (25-100 microM) induced cell death via a mechanism which exhibited morphological and biochemical characteristics of apoptosis, including chromatin condensation, membrane blebbing, and internucleosomal DNA fragmentation. L-DOPA-induced apoptosis was cell and drug-type specific. Toxicity is an intrinsic property of the drug molecule since it was not suppressed by inhibiting conversion of L-DOPA to dopamine. However, L-DOPA toxicity was inhibited by antioxidants, suggesting that activation of apoptosis is mediated by oxygen radicals. Our finding that L-DOPA-induced cell death in vitro occurs via apoptosis explains the lack of evidence supporting its toxicity in vivo, since apoptotic neurons are rapidly phagocytosed in vivo without causing damage to surrounding tissue. Furthermore, since apoptosis is an active cellular program which can be modulated, we suggest clinical approaches for decreasing L-DOPA toxicity, thus preventing acceleration of neuronal damage in Parkinson's disease.

Animals↗
PubMed1985

Planning a statewide genetic screening program: defining program functions to achieve desired outcomes.

When responsibility for administering the Genetic Screening Program in Georgia was transferred from an academic institution to state authority in 1982, the need was identified to reassess program planning. Accordingly, a cooperative effort was initiated between the Director of the Genetic Screening Program and representatives of the Centers for Disease Control to define desired program outcomes and the functions that should be performed to achieve these outcomes. This cooperative effort resulted in the development of specific and measurable outcomes for Georgia's Genetic Screening Program. These desired outcomes indicate the degree of reduction in morbidity and mortality associated with genetic diseases the Program is expected to achieve within a specified period of time. The major actions that should be taken to achieve these outcomes were also identified and delineated in sequence using flowchart format. These explicit descriptions of desired program outcomes and the functions necessary to achieve these outcomes provide the Genetic Screening Program Director with a valuable resource to use in planning program activities and assessing the extent to which the Program is successful in achieving its overall goal of reducing morbidity and mortality associated with genetic diseases.

Anemia, Sickle Cell↗
PubMed1996

Immunopharmacology of rapamycin.

The potent immunosuppressive drugs FK506 and rapamycin interfere with signal transduction pathways required for T cell activation and growth. The distinct inhibitory effects of these drugs on the T cell activation program are mediated through the formation of pharmacologically active complexes with members of a family of intracellular receptors termed the FK506 binding proteins (FKBPs). The FKBP12.FK506 complex specifically binds to and inhibits calcineurin, a signaling protein required for transcriptional activation of the interleukin (IL)-2 gene in response to T cell antigen receptor engagement. The FKBP12. rapamycin complex interacts with a recently defined target protein termed the mammalian target of rapamycin (mTOR). Accumulating data suggest that mTOR functions in a previously unrecognized signal transduction pathway required for the progression of IL-2-stimulated T cells from G1 into the S phase of the cell cycle. Here we review the immunopharmacology of rapamycin, with particular emphasis on the characterization of mTOR.

Animals↗
PubMedDate not supplied

Effect of once-a-week training program on physical fitness and metabolic control in children with IDDM.

To examine whether a physical activity program could improve physical fitness and glycemic control, 32 children and adolescents with insulin-dependent diabetes mellitus (IDDM) were examined before the program and 3 mo later. Fifty percent of the subjects (n = 16) participated in the training for 1 h/wk (exercise group), whereas the remaining subjects were engaged in nonphysical activities for an equal amount of time (nonexercise group). Age of the subjects ranged from 8.2 to 16.9 yr, (mean 11.9 yr), with mean duration of diabetes 0.6-13.1 yr (5.2 yr). During the 3-mo program peak oxygen consumption (VO2) rose from 40.0 to 43.8 ml.min-1.m-2 (P less than .01) in the exercise group but only by 1.3 ml.min-1.m-2 in the nonexercise group (NS). Metabolic control did not improve in either group, with glycosylated hemoglobin level rising from 9.8 to 10.5% (P less than .01) in the exercise group and from 9.4 to 9.7% (NS) in the control group. When subjects were stratified according to their participation, metabolic control was significantly better among diabetic subjects participating frequently (greater than or equal to 11 of 13 sessions) than among those participating infrequently (less than 11 of 13 sessions), regardless of the type of activity. It was concluded that a training program of 1 h/wk for 3 mo does improve physical fitness but not the metabolic control of diabetes. On the other hand, glycemic control appears to be best among diabetic subjects who are motivated to participate in any kind of program related to the treatment of their disease.

Adolescent↗
PubMed1982

Social activation of the elderly. A social experiment.

Social isolation and understimulation are considered to be major problems among institutionalized aged. This article describes an 'activation' program for elderly people living in a senior citizen apartment building. The intention of the research team was to devise a program together with the elderly and the staff, the goals being to increase social activation and self-dependence among the elderly. The program devised was implemented within the apartment's existing financial framework, involving no additional costs, overtime work or external resources. The program was designed in such a way as to allow for measurement of social activation in both the experimental and control groups. This report focuses primarily on the problems which arose in the personnel group in conjunction with the program. Evaluation of these problems was carried out by means of tape-recorded personnel meetings. This paper presents the analysis of these recordings. It was of major importance to the program that any organizational changes be enacted only on the initiative of the elderly and the staff themselves. The results show that it is possible, with relatively simple and inexpensive methods, to stimulate the elderly's interests and counteract social isolation and understimulation.

Aged↗
PubMed1979

Cost containment education efforts in United States medical schools.

Noting the increasing nationwide concern with factors relating to rising health care costs, the Association of American Medical Colleges surveyed 119 U.S. medical schools in the summer of 1978 to ascertain the degree of program activity in the area of cost containment education. A 100 percent response was achieved. An analysis of this data indicates that considerable activity is underway. Forty-one institutions (34 percent) have programs underway or planned specifically to teach health care cost containment to undergraduate medical students or residents or both. The majority of such programs were introduced during the past two years. The costs of such programs are fairly modest, averaging $22,680 per year. Respondents indicated that further activities might be enhanced by development of a primer for faculty and students on elements of cost containment education and the organization of a series of regional workshops related to this subject.

Cost Control↗
PubMed1995

Issues in estimating the cost of innovative mental health programs.

This paper reviews problems encountered in estimating the unit cost of services provided by innovative mental health programs and illustrates methods for addressing these problems. Generally, the cost of a health care service is determined by identifying all resources used in its production and the cost of those resources. These costs are divided by appropriate workload measures to determine the cost per unit of service or per client. Issues that must be addressed include: 1) direct program costs; 2) indirect costs (including administration and capital costs); 3) program resources used to support research and other non-program activities; and 4) identification of "typical" workloads as the program is implemented. Application of these methods is illustrated with data from a multi-site study of intensive psychiatric community care conducted at nine Department of Veterans Affairs Medical Centers in the Northeast. A sensitivity analysis revealed that estimates of program costs vary by 59% over the entire program, and from 17%-168% at individual sites, depending on which cost estimation methods were included. The average cost of case management in this program varied considerably across sites, primarily reflecting differences in caseload size and staffing levels. Adjusting for inflation, the cost of this program falls below the cost of other published intensive community programs.

Community Mental Health Services↗
PubMed1975

Evaluating family planning program effectiveness and efficiency.

This article proposes an integrated in-house evaluation model for family planning programs. The model is designed to meet the need of program management for an operational and internal evaluation system suited to the ongoing character of program activities and focused on the feedback of information for program planning. The ideas presented are applied to the context of the Albany County Family Planning Service, Inc., Wyoming.

Adolescent↗
PubMed1993

Bone marrow transplantation at the University of Nebraska Medical Center.

The bone marrow transplant program at UNMC is currently one of the most active programs in the country. The benefits to patients who are cured of disease by transplantation cannot be measured. The large volume of clinical and basic science research related to transplantation has enhanced the academic stature of UNMC. The combination of patient care, education, clinical research, and basic science research provides an excellent model for the operation of an academic medical institution.

Adult↗
PubMed1996

Oligonucleotides induce apoptosis restricted to the t(14;18) DHL-4 cell line.

Most human follicular B-cell lymphomas are associated with t(14;18) chromosome translocation that joins the bcl-2 gene with the IgH locus. This hybrid gene causes upregulation of BCL-2 protein expression, endowing cells with survival advantage. Although early BCL-2 overexpression is definitely responsible for immortalization/transformation, its exact role in the overt transformation as well as in the maintenance of the tumor phenotype is not known. The capacity of oligodeoxynucleotides (ODN) to modulate gene expression specifically has been exploited to downregulate the overexpression of BCL-2 protein in the SU-DHL-4 human follicular B-cell lymphoma line by the use of sense ODN or antisense ODN or antisense ODN designed to encompass the unique nucleotide sequence in the fusion region of the hybrid transcript. The specific downregulation of the bcl-2 transcript and of the relevant BCL-2 protein in the treated cells activated programed cell death and inhibited growing cells. The antitumor activity was restricted to the DHL-4 cell line carrying the specific nucleotide sequence at the bcl-2/IgH joining region. Thus, DHL-4 lymphoma cells derived from the acute phase of human follicular B-cell lymphoma, although endowed with additional activated oncogenes, were growth inhibited by bcl-2 downregulation with additional activated oncogenes, were growth inhibited by bcl-2 downregulation in a genetically restricted fashion. The biological activity was exerted exclusively by ODNs synthesized in the sense orientation. The sense ODNs have been proposed to anneal the hybrid bcl-2/IgH antisense RNA as identified in this study.

Amino Acid Sequence↗
PubMed1996

Gender differences in physical activity and determinants of physical activity in rural fifth grade children.

This study determined if gender differences in physical activity could be accounted for by differences in selected social-cognitive determinants of activity behavior. Some 334 fifth grade, predominantly African-American students provided information regarding after-school physical activity and the hypothesized determinants of activity behavior. Boys reported significantly greater participation in vigorous ( > or = 6 METs) and in moderate to vigorous ( > or = 4 METs). Relative to girls, boys demonstrated higher levels of physical fitness, greater self-efficacy in overcoming barriers to physical activity, greater amounts of television watching, and higher levels of participation in community sports and physical activity organizations. When mean physical activity scores for girls and boys were adjusted for the effects of these determinant variables, the significant gender difference in physical activity remained. However, adjustment for self-efficacy in overcoming barriers and community sports reduced the gender gap by 5% and 7%, respectively. In contrast, adjustment for television watching increased the gender gap by about 8%. Results indicated perceived confidence in overcoming barriers to physical activity and participation in community physical activity programs are factors related to the gender difference in physical activity.

Child↗
PubMed1978

Identification of the structural gene for the hook subunit protein of Escherichia coli flagella.

Previous studies showed that the structural gene for the flagellar hook subunit protein (molecular weight 42,000) was one of a group of flagellar genes located on the Escherichia coli genome near pyrC. Several lines of evidence indicate that the flaK gene is the structural gene for the hook subunit protein. Fla+ strains that were insensitive to chi infection could be isolated as revertants of an FlaK- amber mutant strain but from no other Fla- strain. The hook subunit proteins isolated from such chi-sensitive revertants of the FlaK- strain were shown to be antigenically and electrophoretically different from the hook protein isolated from the wild-type strain. Thus, reversion of a mutation in the flaK gene resulted in alteration of the structure of the hook protein. Furthermore, in programming experiments with hybrid lambda containing flagellar genes, lambdafla with flaK genetic activity programmed the synthesis of a 42,000-molecular weight protein, whereas lambdafla without flaK genetic activity did not.

Bacterial Proteins↗
PubMed1991

Randomized 4-week exercise program in patients with impaired left ventricular function.

BACKGROUND: This study was designed to determine the controlled effects of a short-term exercise rehabilitation program on patients with moderate-to-severe left ventricular dysfunction after a recent myocardial infarction. METHODS AND RESULTS: Thirty-nine male patients 51 +/- 8 years old with a large anterior myocardial infarction less than 10 weeks old were recruited for the study. The patients were randomly assigned to either one of two training or control groups on the basis of their resting ejection fraction: training, less than 30%; control, less than 30%; training, 31-50%; or control, 31-50%. Patients were evaluated for filling pressures, radionuclide ventriculography, heart volume, echocardiography, and work capacity. Patients who underwent training participated in an intensive 4-week in-hospital exercise program, whereas the control patients were restricted to a minimal activity program. Results indicated that there were no significant improvements in resting, submaximal, and maximal hemodynamic measurements as a result of the program. Mean work capacity and peak oxygen consumption improved significantly in the less-than-30% training group but was accompanied by a significant increase in mean pulmonary wedge pressure. Resting ejection fraction improved markedly in both less-than-30% training and control patients, but ejection fraction measures were not associated with work capacity. Training did not cause further deterioration in ventricular function. CONCLUSIONS: It was concluded that in the present study, exercise training had little or no effect on hemodynamic measurements and that the training effects achieved in patients with left ventricular dysfunction are most likely due to corrected impaired vasodilation, not necessarily to cardiac function. The importance of using a control group in this type of study and the wide interindividual variations in training responses are emphasized.

Exercise Therapy↗
PubMed1994

An examination of demographic, socio-cultural, and health differences between congregate and home diners in a senior nutrition program.

Building upon prior research, this study investigates characteristics of participants in a senior nutrition program in Hillsborough County, Florida. The Senior Citizens Nutrition and Activities Program serves approximately 2,600 meals per day to county residents 60 years of age and over. In this study, a sample of 1,071 participants are surveyed for background characteristics, interpersonal relationships and emotional closeness, health and economic condition, emotional condition, and participation in the program. Crosstabular analyses are performed on the collected data with age, sex, and race controlled. The results indicate that the program is reaching its goals of promoting good health among the older population of Hillsborough County by providing nutritious meals and reducing social isolation, which often accompanies aging.

Aged↗
PubMed1981

Alcoholism treatment in Canada: a review of current programs and policy issues.

An overview of the specialized alcoholism treatment field in Canada is presented based on a 1976 national survey of 338 programs. Descriptive information on these programs is presented to provide an understanding of the state of current treatment efforts and to identify emersent policy issues in this field. Programs activities are described under six headings: (1) the pattern of program development, (2) types of treatment agencies, (3) treatment capacity and utilization, (4) the characteristics of persons using treatment services, (5) approaches employed in treatment, and (6) program costs and financing of alcoholism treatment. Findings from the national study are related to three policy issues: access, quality, and cost. The need for future research aimed at these issues is discussed.

Alcoholism↗
PubMedDate not supplied

The medical and surgical determinants of heart transplantation outcomes: the results of a consensus survey in the United States.

Heart transplantation may well be the most successful transplantation procedure performed today. One-year patient survival rates now exceed 80%. Many factors are thought to account for differences in outcomes among transplantation centers. No attempt has been made to assess consensus among transplantation program directors regarding the major determinants of patient outcome. In the National Cooperative Transplantation Study we evaluated consensus through a detailed survey of all heart transplantation programs active in the United States in 1988. Of the eligible programs, 104 (91%) returned completed surveys. Data on the medical and surgical determinants of outcomes have been analyzed descriptively. Considerable consensus occurred among program directors about the importance of several factors. For example, over 90% of the respondents felt that heart biopsy should be used as the standard rejection monitoring technique and that left and right heart catheterization should be performed annually with coronary arteriography. Over 60% believed that the availability of a left ventricular assist device for temporary use would also enhance patient outcome. Several approaches were considered to have little beneficial effect on outcome. These included cytoimmunologic monitoring and electrocardiography as standard rejection monitoring techniques. Nearly one half of the respondents opposed steroid discontinuation after transplantation. On several other approaches there was a lack of consensus including the use of heterotopic heart transplantation and conversion from cyclosporine because of renal dysfunction. Consensus conferences are now regarded as a means by which technologic innovations can be evaluated and medical practice guidelines can be set. This analysis suggests that consensus is a useful approach toward assessing medical and surgical practices in heart transplantation.

Data Collection↗
PubMed1994

Physical activity patterns in American high school students. Results from the 1990 Youth Risk Behavior Survey.

OBJECTIVE: To assess by self-reported participation in vigorous physical activity, the quantity and quality of school physical education, team sports, and television watching among 11,631 American high school students. RESULTS: Of all students in grades 9 through 12, 37% reported engaging in 20 minutes of vigorous physical activity three or more times per week. Participation in vigorous physical activity was higher among boys than girls (P < .01) and higher among white students than among those of other races and ethnic groups (P < .01). Overall, 43.7% of boys and 52% of girls reported that they were not enrolled in physical education classes. Of the students who reported attending physical education class during the past 2 weeks, 33.2% reported exercising 20 minutes or more in physical education class three to five times per week. In contrast, rates of participation in varsity and junior varsity sports remained constant across grade levels, but participation in recreational physical activity programs showed a lesser magnitude and also decreased with advancing grade. More than 70% of students reported spending at least 1 hour watching television each school day, and more than 35% reported watching television 3 hours or more each school day. CONCLUSIONS: Participation in vigorous physical activity and physical education class time devoted to physical activity are substantially below the goals set in Healthy People 2000. As students move toward graduation, we observed disturbing declines in participation in community recreation programs and overall vigorous activity. Students appear to spend considerably more time watching television than participating in physical activity. Public health efforts should focus on increasing the physical activity levels of our youth to enhance their current well-being and to reduce the risks of future chronic disease.

Adolescent↗