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PubMed2003

Region of caspase-3 activation and programmed cell death in the early development of the mouse forebrain.

Caspase-3-deficient 129/Sv mice show hyperplasia of the brain at embryonic (E) day 10.5-12.5, but caspase-3-deficient C57L/B6 mice do not. We examined the relationship between activation of caspase-3 and programmed cell death (PCD) during forebrain development of various mouse strains (129/Sv, ICR, C57L/B6, and CBA) using terminal deoxytransferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) and immunostaining with antiserum against the caspase-3 (anti-m3D175) cleavage site. A number of anti-m3D175 positive cells and TUNEL positive cells were detected in the ventral side of the forebrain of 129/Sv and ICR mice at E8.5-9 but not in C57L/B6 and CBA mice. Ac-DEVD-MCA cleavage activity, a caspase-3-like activity, also suggests the preferential activation of caspase-3 in the ventral forebrain of ICR mice but not in C57L/B6 mice. Developmental changes of TUNEL and anti-m3D175 reactivities were essentially similar during brain morphogenesis of ICR and 129/Sv mice. The number of TUNEL/anti-m3D175 positive cells decreased in the neuroepithelium of the ventral forebrain at E9.5 before generation of the medial ganglionic eminence (MGE). TUNEL and/or anti-m3D175 reactivity was slightly detectable in the MGE at E10.5, from which neuroprogenitor cells follow a tangential migratory route to the cortex. Activation of caspase-9 was also immunohistochemically detected in the ventral forebrain at E8.5-9, suggesting that activation of caspase-3 and caspase-9 occurs in the PCD of this region. Thus, it is likely that decreased cell death in the ventral forebrain of caspase-3- and caspase-9-deficient 129/Sv mice increases the number of neuroprogenitor cells in the MGE, leading to hyperplasia of the forebrain.

Animals↗
PubMed2001

Effectiveness of family care intervention program on activity of daily living among disabled patients.

The objective of this prospective study was to compare the improvement of activity of daily living (ADL) scores between two groups of disabled patients who participated in a family care intervention program. 137 patients were selected from health stations and Activity of Daily Living (ADL) scores were assessed eight times over a period of 22 weeks. Family caregivers were trained to provide home nursing care for the disabled. The patients were divided into two groups: early-stage (intervention started less than 6 months from diagnosis) and late-stage (intervention started 7-24 months from diagnosis). Over the duration of the intervention program, the results, using ANCOVA test, showed that the ADL score of the early-stage had group increased by 12.9, compared to the later-stage group, which increased by 3.0 (p < .000). At one-year follow-up, the ADL score of the early-stage group increased by a greater extent (6.2) than the later-stage group (1.3). The factors that affected ADL scores of the survivals were as follows: age, baseline ADL score and duration of disability. The authors conclude that the intervention program was most effective in improving ADL score when intervention was implemented early.

Activities of Daily Living↗
PubMed1997

The effectiveness of an early active intervention program for workers with soft-tissue injuries. The Early Claimant Cohort Study.

STUDY DESIGN: A prospective cohort of approximately 1600 injured workers off work because of soft-tissue musculoskeletal problems was followed for 1 year through a series of structured telephone interviews. OBJECTIVE: To determine the effectiveness of a Workers' Compensation Board-sponsored early, active, exercise and education program based in the community in comparison to "usual" care. SUMMARY OF BACKGROUND DATA: The program established in 1990 was available in more than 100 clinics. Results from an earlier pilot study indicated lower overall claims costs for workers attending the program compared with non-attenders. METHODS: Subjects were recruited at the time of Workers' Compensation Board claim registration. Routinely collected data and self-reported responses to demographic, quality-of-life, functional status, pain, recovery expectations, and workplace response to injury questions were used to determine selection factors for community clinic attendance. Economic and non-economic outcomes were compared for clinic attenders and non-attenders. RESULTS: For the 885 male and female new back problem cases in the study, overall clinic attenders were not systematically different from non-attenders at baseline. Analysis of duration of benefits showed no significant difference between attenders and non-attenders, although health care costs for clinic attenders were significantly higher. Functional status, health-related quality-of-life, and pain measures all improved significantly throughout time for both groups, bit there were no statistically significant differences in rate of improvement. CONCLUSION: There was no advantage from the program compared with usual care on the outcomes measured-a finding consistent with recent studies that examined the longer-term effectiveness of other interventions in the first few weeks of back pain symptoms.

Aged↗
PubMed2003

A radiation protection program prospectus based on the collection of 10 years of key performance indicator data.

In 1992, the University of Texas Health Science Center at Houston Radiation Safety Program began assembling data on a monthly basis that described various program activities. At the end of calendar year 2002, a decade of data had been collected, so the information was summarized into a novel program prospectus, displaying various indicator parameters in a format similar to that used in a commercial enterprise prospectus provided to potential investors. The consistent formatting of the data afforded a succinct and easily digestible snapshot of program activities and trends. Feedback from various program stakeholders, even those unschooled in radiation safety matters, was overwhelmingly positive. The prospectus aided in communicating the scope of work undertaken by the program, and has helped maintain program support, even in challenging economic times. The data summary is also proving to be useful in making future projections regarding program needs.

Academic Medical Centers↗
PubMed2000

Prevention validation and accounting platform: a framework for establishing accountability and performance measures of substance abuse prevention programs.

The field of substance abuse prevention has neither an overarching conceptual framework nor a set of shared terminologies for establishing the accountability and performance outcome measures of substance abuse prevention services rendered. Hence, there is a wide gap between what we currently have as data on one hand and information that are required to meet the performance goals and accountability measures set by the Government Performance and Results Act of 1993 on the other. The task before us is: How can we establish the accountability and performance measures of substance abuse prevention programs and transform the field of prevention into prevention science? The intent of this volume is to serve that purpose and accelerate the processes of this transformation by identifying the requisite components of the transformation (i.e., theory, methodology, convention on terms, and data) and by introducing an open forum called, Prevention Validation and Accounting (PREVA) Platform. The entire PREVA Platform (for short, the Platform) is designed as an analytic framework, which is formulated by a collectivity of common concepts, terminologies, accounting units, protocols for counting the units, data elements, and operationalizations of various constructs, and other summary measures intended to bring about an efficient and effective measurement of process input, program capacity, process output, performance outcome, and societal impact of substance abuse prevention programs. The measurement units and summary data elements are designed to be measured across time and across jurisdictions, i.e., from local to regional to state to national levels. In the Platform, the process input is captured by two dimensions of time and capital. Time is conceptualized in terms of service delivery time and time spent for research and development. Capital is measured by the monies expended for the delivery of program activities during a fiscal or reporting period. Program capacity is captured by fourteen measurement units, tapping into the dimensions of staff resources and community assets. Staff resources are, in turn, operationalized in terms of staff size, staff certification status, staff turnover rate, and the accreditation status of a provider agency. Community assets are operationalized by the number of community centers accessible to the funded agency, number of formalized teams or antidrug coalitions active in the catchment area, and other social/human services providers with whom the prevention agency has formalized networks. The totality of process output from all sources of program activities is reduced to eighteen classes of measures. These are operationalized by thirty-three summary measures. Some of these include: total count of events facilitated; total number of clients served; average number of clients served per event; clients served by single and multiple program sessions; classification of target population in terms of the severity of risk as defined by the Institute of Medicine; age groups and race/ethnicity of clients served; number of program participants retained by recurring programs; number of clients who have completed the program; penetration rates to the target population; client attrition rates; average referral rates per provider per time interval; referral success rates; and so on. All process output measures specified in the Platform are derived from two broad classes of events classified as either products or services. The collectivity of these measures is expected to present a cost-effective, parsimonious, yet comprehensive picture of the entire spectrum of the process output, i.e., "what came out of the program as program activities". For the measurement of performance outcomes, two types of data are incorporated into the Platform: outcome data from individuals and the behavior (or performance) of social indicators from aggregated data bases. Individual data are used to evaluate the outcome of substance abuse programs

Accounting↗
PubMed1992

Matching services to needs. Vocational services for substance abusers.

Problems with employment are common among individuals with substance use disorders, yet comprehensive vocational services are not generally available to them, and vocational interventions are often not matched to their specific needs. This article describes the wide range of vocational problems found among individuals with substance use disorders and the elements of a recently funded vocational program for patients in outpatient and residential drug and alcohol treatment programs. Data are presented describing program activity and documenting program effectiveness for the first 2 years of operation of the program. Three case histories are presented to illustrate the types of services delivered and the matching of services delivered to specific, identified client needs (see Case Histories).

Adult↗
PubMed2003

Caspase-like activity in programmed nuclear death during conjugation of Tetrahymena thermophila.

Apoptosis, or programmed cell death, is common in a variety of eucaryotes, from unicellular protozoa to vertebrates. The ciliated protozoan Tetrahymena thermophila has a unique apoptosis-like nuclear death during conjugation, called programmed nuclear death. This death program involves nuclear condensation (pyknosis) and oligonucleosomal DNA fragmentation in the parental macronucleus. Subsequently, the condensed nucleus is entirely resorbed in the autophagosome. Here we demonstrate that caspase-8- and -9-like activity was detected, but no caspase-3-like activity, by in vitro assay during the nuclear resorption process, suggesting that caspase-like activity is associated with both programmed cell death and apoptosis-like nuclear death in Tetrahymena. The use of indicator dye to detect the loss of mitochondrial membrane potential suggested the uptake of mitochondria and the degenerating macronucleus by the autophagosome. An involvement of mitochondria in the programmed nuclear death is discussed.

Animals↗
PubMed1995

Tyrosine phosphorylation participates in peripheral T-cell activation and programmed cell death in vivo.

T-cell antigen receptor (TCR), which is not itself a protein tyrosine kinase (PTK), is thought to be associated with at least two SRC-like PTKs, P59fyn and ZAP-70. Activation of these PTKs is required for T-cell signal transduction. The aim of the present study was to determine the roles of PTKs in peripheral T-cell activation, induced by in vivo bacterial superantigen administration. We demonstrated that in vivo staphylococcal enterotoxin B (SEB) administration induced an enhanced tyrosine phosphorylation in peripheral spleen T cells undergoing a programmed cell death. In vitro immunecomplex kinase assay using antibody against P59fyn showed increased fyn kinase activity in SEB-stimulated spleen T cells. We examined the effect of PTK-specific inhibitors on DNA fragmentation and programmed cell death of V beta 8 positive T cells following in vitro culture of SEB-primed spleen T cells. Our results indicated that pretreatment of SEB-activated T cells with PTK inhibitors reduced DNA fragmentation and programmed cell death of V beta 8 positive T cells. These findings suggest that PTK plays an important role in activation and apoptosis of peripheral T cells induced by in vivo SEB administration.

Animals↗
PubMed1992

Influence of lidocaine on human muscle sympathetic nerve activity during programmed electrical stimulation and ventricular tachycardia.

Lidocaine directly affects conduction and refractoriness of ventricular myocardium, and may also indirectly affect these electrophysiologic properties by inhibition of cardiac sympathetic nerve traffic. Both effects may play important roles in preventing ventricular arrhythmias in humans. To determine if lidocaine has a direct effect on sympathetic nerve activity, the effects of a 100 mg lidocaine bolus followed by a 2 mg/min infusion of lidocaine on muscle sympathetic nerve activity was assessed in seven patients during programmed ventricular stimulation with single extrastimuli (premature ventricular contractions [PVCs]) in sinus rhythm, and in seven patients during induced hemodynamically stable monomorphic ventricular tachycardia. During single extrastimuli, the mean (+/- SEM) area of PVC-associated bursts of sympathetic nerve activity was unaffected by lidocaine (1101 +/- 16 units pre-lidocaine versus 1075 +/- 19 units following lidocaine; p = 0.30). Likewise, the transient decrease in blood pressure with induced PVCs was similar before and after lidocaine infusion (p = 0.46). In seven patients with induced monomorphic ventricular tachycardia, tachycardia cycle length did not change after the lidocaine bolus (393 +/- 18 versus 399 +/- 17 msec; p = 0.34) but increased during lidocaine maintenance infusion (428 +/- 17 msec; p = 0.01). After induction of ventricular tachycardia, systolic pressure decreased from 150 +/- 6 to 117 +/- 9 mm Hg at 1 minute of tachycardia, to 109 +/- 6 mm Hg during the lidocaine bolus, and rebounded to 126 +/- 8 mm Hg during the lidocaine maintenance infusion (p = 0.04, bolus versus infusion).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1983

An experimental study of social isolation of elderly people: psychoendocrine and metabolic effects.

Psychoendocrine and metabolic effects of social isolation and understimulation in real life were examined in a controlled study of 60 elderly people representative of their age group. Together with the staff and the elderly, a social activation program was formed at a senior citizen apartment building. Half of the elderly were part of this activation program (experimental group). The other half constituted the control group. Blood sampling and psychosocial testing were performed immediately before and after 3 and 6 months of social activation. Social activation increased threefold in the experimental group. Height decreased in the control group compared to the experimental subjects. Plasma levels of testosterone, dehydroepiandrosterone, and estradiol increased significantly in the experimental group over the 6-month period compared to the control group. The most pronounced increase took place during the initial 3 months. Hemoglobin A1c decreased significantly in the experimental group over the 6-month period compared to the control group. In this preliminary study it is concluded that social isolation and understimulation may be associated with a wide range of psychophysiologic effects in elderly people.

Aged↗
PubMed1978

Tuftsin (an Ig-associated tetrapeptide) triggers the immunogenic function of macrophages: implications for activation of programmed cells.

The immunoglobulin heavy-chain-associated tetrapeptide, tuftsin (Thr-Lys-Pro-Arg), known for its phagocytosis-stimulating activity, was found to augment the antigen-specific, macrophage-dependent education of T lymphocytes. The investigation of stereospecific characteristics of the tetrapeptide, by use of structural analogs with different modifications, revealed strict structural requirements for eliciting the immunogenic activity of macrophages. It was found that the most important moiety for its activity is the dipeptide Pro-Arg. This finding is of interest in view of the appearance of this particular dipeptide in other bioregulatory peptides, including many of the peptide hormones. The significance of the appearance of a common structure in such molecules, which may act through specific receptors on different target cells, is discussed.

Amino Acid Sequence↗
PubMed1988

A community outreach training program for pediatric residents and medical students.

In 1982 the Division of Community Pediatrics of the University of North Carolina at Chapel Hill began a new training program for all first-year pediatrics residents and fourth-year medical students taking an ambulatory pediatrics elective. The program was designed to introduce the trainees to community resources for children and increase their knowledge of the factors affecting children's development. During their regular hospital clinic rotations, the trainees spend approximately one-third of their time in program activities that involve 25 community agencies. Educational packets (consisting of books, journal articles, films, slides, videotapes, self-instruction materials, manuals for developmental tests, and/or agency materials) are provided for each program component. At the end of each one-month rotation of program activities, the trainees meet individually with the program director and coordinator to discuss the trainee's experiences and reactions and to identify strengths and weaknesses of the program components.

Child↗
PubMed1994

Development and impact of the Gene-Tox-Program, genetic activity profiles, and their computerized data bases.

This invited historical review traces the development and impact of two major data bases in the field of genetic toxicology. Discussed from a personal perspective are the Environmental Protection Agency (EPA) Gene-Tox Program and the EPA/International Agency for Research on Cancer Genetic Activity Profiles (GAPs) and their respective data bases. Whereas Gene-Tox was focused on the assessment of short-term tests and their role in predicting carcinogens and mutagens, GAPs and the GAP data base were designed specifically to aid in the evaluation of individual chemicals. Both data bases have been computerized. Gene-Tox is available on TOXNET and GAP is available in a personal computer format from the author. The Gene-Tox and GAP data bases appear to have had substantial impact, particularly on hazard identification activities in cancer risk assessment.

Carcinogenicity Tests↗
PubMed1991

[Lateral instability of the ankle joint (2). Active training programs can prevent surgery].

One hundred consecutive patients with chronic lateral functional instability of the ankle were treated non-operatively with physiotherapy (active range-of-motion training, strengthening exercises and co-ordination training with a tilt-board). All patients were evaluated functionally with a special rating scale, and radiologically with standardised stress radiographs measuring anterior talar translation (ATT) and talar tilt (TT). Excellent or good functional results were obtained in 49 of the patients, fair or poor in the remainder. The outcome was better in those with painful functional instability or mild mechanical instability, while those with more pronounced mechanical instability required further treatment (i e, reconstructive surgery). Of 10 patients with generalised joint laxity, only fair or poor results were obtained in seven, all of whom had mechanical instability.

Adult↗
PubMed1996

HLA class II signaling mediates cellular activation and programmed cell death.

The class II human leucocyte antigens (HLA class II) are principally peptide presentation molecules. Signal transduction by these molecules has also been shown to transmit activation signals in both B and T lymphocytes by a pathway including protein tyrosine kinase activation, an intracellular calcium flux, and both the activation and transcriptional regulation of protein kinase C (PKC) isoforms. Apoptosis can also result from human leukocyte antigen class II stimulation. Inhibitors of gene transcription were used to inhibit activation and, therefore, to distinguish the signal transduction pathways important for apoptosis. This approach provided evidence that cellular activation and apoptosis undertook separate signaling pathways, and that PKC and intracellular calcium were shared between the two pathways, while tyrosine kinase activity was essential for cell activation. Further studies using cord blood B cells showed that these cells were incapable of generating a calcium flux after HLA class II ligation and were not subject to cell death. The importance of sustained levels of calcium for programmed cell death (PCD) was underlined since the restoration of a calcium flux enabled PCD of cord blood B cells via HLA class II. These results demonstrate that HLA class II stimulation initiates two distinct signal transduction pathways.

Adult↗
PubMed1995

Integrated control of seed maturation and germination programs by activator and repressor functions of Viviparous-1 of maize.

The Viviparous-1 (VP1) transcriptional activator of maize is required for abscisic acid induction of maturation-specific genes late in seed development leading to acquisition of desiccation tolerance and arrest in embryo growth. Here, we show that VP1 also inhibits induction of the germination-specific alpha-amylase genes in aleurone cells of the developing seed and thereby appears to be involved in preventing precocious hydrolyzation of storage compounds accumulating in the endosperm. In developing seeds of the somatically instable vp1-m2 mutant, hydrolase activity was derepressed specifically in endosperm sectors underlying vp1 mutant aleurone. A barley alpha-amylase promoter-GUS reporter construct (Amy-GUS) was induced in developing vp1 mutant aleurone cells but not in wild-type aleurone cells. Moreover, transient expression of recombinant VP1 and vp1 mutant aleurone cells strongly inhibited expression of Amy-GUS and thus effectively complemented this aspect of the mutant phenotype. VP1 specifically repressed induction of Amy-GUS by the hormone gibberellic acid in aleurone of germinating barley seeds. Deletion of the acidic transcriptional activation domain of VP1 did not affect the inhibitory activity, indicating that VP1 has a discrete repressor function. Hence, physically combining activator and repressor functions in one protein may provide a mechanism to integrate the control of two normally consecutive developmental programs, seed maturation and seed germination.

DNA-Binding Proteins↗
PubMed1998

Effects of a three-month active rehabilitation program on psychomotor performance of lower limbs in subjects with low back pain: a controlled study with a nine-month follow-up.

Proper psychomotor performance is needed in work and in activities of daily living, but among subjects with low back pain this area has been studied little. The present purpose was to evaluate the effect and permanence of a 3-mo. physical exercise program on the psychomotor performance of lower limbs in subjects with low back pain. The associations between psychomotor performance and intensity of low back pain and subjective disability were also evaluated. 90 subjects with nonspecific, subacute low back pain were assigned to one of the three groups: one given three months intensive training, one home exercise, or the control group. Four measurement sessions were made during the 1-yr. study. Psychomotor speed of lower limbs was analyzed with Choice Reaction Time, Movement Time, and Total Response Time. Flight Time of a vertical static jump was also measured. Muscle strength was assessed with conventional methods from trunk, lower limbs, and hand. Intensity of Current Back Pain was analyzed with the Borg scale. Subjective disability was evaluated with the Oswestry Index. Analysis showed that muscle strength and back pain intensity had associations with psychomotor performance but subjective disability or physical activity did not affect it noticeably. There were no changes in Choice Reaction Time, but Total Response Time and Movement Time decreased and Flight Time increased for all subjects. In the first postintervention measurement the home exercise group had significantly lower Movement Time than the intensively trained group. Back Pain Intensity decreased in both exercise groups for those subjects whose psychomotor performance values were below the mean value for the sample.

Adult↗