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PubMed1988

Activation of monocytes--more than one process. Differential effect of cytokines on monocytes.

Monocytes and macrophages respond to a number of exogenous agents by alterations in metabolism and gene expression in a process loosely called 'activation'. The question arises whether these alterations in cellular activity are the pleiotropic effects of one programmed activation process or result from separately programmed activation pathways. We report that certain cytokines (interleukin 1 (IL-1 alpha, IL-1 beta) and interleukin 2 (IL-2] which all activate monocytes, induce the synthesis of thromboplastin (TPL) and (IL-1 beta only) factor VII. Interferon-gamma (IFN-gamma) and tumour necrosis factor alpha (TNF alpha) do not induce monocyte procoagulant activity, although they both activate monocytes in several respects. Our data thus show that different states of activation are induced. Similar observations have been made by others using different systems.

Biological Products↗
PubMed1989

Growth factors and membrane depolarization activate distinct programs of early response gene expression: dissociation of fos and jun induction.

A set of early response genes has been identified whose transcription in fibroblasts is rapidly induced in response to growth factors. Prototype members of this group, c-fos and c-jun, encode products that form a heterodimer and have been implicated in the regulation of gene expression and cell growth. It is thought that other early response genes also encode critical mediators of the cell's response to external stimuli. We have used PC12 pheochromocytoma cells as a model system to test the hypothesis that different extracellular signals induce distinct patterns of expression of early response genes. Our results indicate that membrane depolarization, induced either by potassium chloride or by the neurotransmitter analog nicotine, activates a program of gene expression distinct from that activated by nerve growth factor or epidermal growth factor. Notably, c-fos and c-jun activation can be dissociated; whereas c-jun is coinduced with c-fos and jun-B after growth factor stimulation, membrane depolarization activates c-fos and jun-B without stimulating c-jun. Fos may therefore form transcription complexes with alternative cofactors under different stimulation conditions. nur/77 and zif/268, which encode putative transcription factors, also show markedly different responses to growth factors and depolarization. We conclude that multiple nonconvergent signal transduction pathways control early response gene expression. Our findings also indicate that the diversity and specificity of cellular response to environmental change can be accounted for by the differential combinatorial induction of a relatively small number of early response genes.

Animals↗
PubMed1986

The Veterans Administration Northwest Regional Health Services Research and Development Field Program: organization, activities, and early outcomes.

In 1982, the Veterans Administration established Health Services Research field programs in each of the six VA regions. Herein, we describe the historical origins, organization, responsibilities, activities, and early accomplishments of one of these programs--the Northwest Regional HSR&D field program. Special reference is made to this program's commitment to health services research relevant to geriatrics and gerontology, including the development of a system-wide agenda for research, information syntheses in geriatrics-relevant health services research topics, and the conduct of funded projects pertinent to care of the elderly. The importance of a medical center location for the field programs is discussed, and early indications of institutional impact are described.

Aged↗
PubMed1988

Activation of programmed cell death in the rat ventral prostate after castration.

The rapid involution of the rat ventral prostate after castration is an active process initiated by removal of the inhibitory effects of androgen on prostatic cell death. The present studies demonstrate that after castration-induced androgen deprivation a series of temporally discrete biochemical events are activated which result in the rapid programmed death of the subset of androgen-dependent cells within the rat ventral prostate. These biochemical steps involve 1) rapid loss of nuclear androgen receptor retention; by 12 h after castration, androgen receptors are no longer detectable in ventral prostatic nuclei; 2) an initial fragmentation of nuclear DNA into low mol wt (less than 1000 basepairs) nucleosomal oligomers which lack intranucleosomal break points; and 3) eventual complete digestion of these nucleosomal oligomers into component nucleotides. Additional studies demonstrate that activation of a Ca2+-Mg2+-dependent endonuclease is associated with this DNA fragmentation. By 4 days after castration, maximal DNA fragmentation is obtained, with 15% of the total nuclear DNA extractable as low mol wt fragments. Proteolytic enzymes are apparently not involved initially in this process, suggesting that DNA fragmentation is a discrete event in, rather than a result of, cell death. Flow cytometric analysis of nuclear DNA content demonstrated that each day after castration, a subpopulation of androgen-dependent cells in rat ventral prostate fragmented all of their genomic DNA, as opposed to the whole population of cells fragmenting an increasing portion of their DNA daily.

Animals↗
PubMed1985

Gerontic occupational therapy--psychological and social predictors of participation and therapeutic benefits.

The purpose of this study was to assess what role psychological and social factors play in predicting the participation of elderly people in a social activation program. Furthermore, the study evaluated the importance of such factors in improving subjects' moods and decreasing feelings of loneliness. Over a six-month period, a social activation program was conducted in a senior citizen apartment building in Stockholm, Sweden. A group of 30 residents from one floor of the building, the experimental group, received the program while a control group of 30 residents from another floor did not. Medical, social, psychological, and behavioral assessments were made immediately before, three months after, and six months after the beginning of the program. Results were that the activity level had increased threefold in the experimental group. Experimental group subjects who initially had a low social activity level and higher scores on the internal-locus-of-control scale had the highest rate of increase in their social activity level. Subjects in the experimental group who initially had a low social activity level, were single or bereaved, scored low on the neuroticism scale, or desired a low level of internal control showed the greatest improvement in mood. Feelings of loneliness decreased the most among those in the experimental group who had a stronger internal locus of control and scored high on pessimistic feelings. Because the program benefited those subjects who initially were the most passive and isolated, it is concluded that gerontic occupational therapy plays an important role in preventing unnecessary social isolation in institutional living.

Aged↗
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↗
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↗
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↗
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↗
PubMedDate not supplied

Use of process evaluation to guide health education in Forsyth County's project to prevent cervical cancer.

The Forsyth County, NC, Cervical Cancer Prevention Project is a 5-year public health education program designed to increase the proportion of black women in the county who are appropriately screened for cervical cancer. In this paper, the authors report on process evaluation--the procedures used to monitor the intervention and to insure that the target population was reached with a high quality, community-based health education program. A system that encompasses documentation of program activities, interviews with women in waiting rooms of primary care providers, semiannual interviews with a panel of approximately 100 women from the target population, and telephone followup with participants in direct education workshops was designed and implemented. Through October 1990, more than 2,100 interviews had been conducted. Data from these activities have facilitated continued development and refinement of educational materials, provided guidance for developing new strategies for reaching the target population, and provided continuous feedback to program managers to allow monitoring the impact of all program activities.

Black or African American↗
PubMedDate not supplied

Activation of programmed cell death by anticancer agents: cisplatin as a model system.

The anticancer drug cisplatin exerts its action as a consequence of interaction with DNA. Cell cycle progression facilitates sensitivity to the drug, but inhibition of DNA synthesis is not necessarily the critical step. Lethally damaged cells can progress to and arrest for several days in the G2 phase of the cell cycle before dying. Certain features of cisplatin-induced cell death, such as chromatin condensation and the activation of a DNA endonuclease, are reminiscent of apoptosis, or programmed cell death. Many other anticancer drugs produce the same phenotypic effects, suggesting that these agents may all interact with the same signal transduction pathway leading to cell death.

Cell Cycle↗
PubMed2025

Boolean matrix logic programming for active learning of gene functions in genome-scale metabolic network models.

Reasoning about hypotheses and updating knowledge through empirical observations are central to scientific discovery. In this work, we applied logic-based machine learning methods to drive biological discovery by guiding experimentation. Genome-scale metabolic network models (GEMs) - comprehensive representations of metabolic genes and reactions - are widely used to evaluate genetic engineering of biological systems. However, GEMs often fail to accurately predict the behaviour of genetically engineered cells, primarily due to incomplete annotations of gene interactions. The task of learning the intricate genetic interactions within GEMs presents computational and empirical challenges. To efficiently predict using GEM, we describe a novel approach called Boolean Matrix Logic Programming (BMLP) by leveraging Boolean matrices to evaluate large logic programs. We developed a new system, [Formula: see text], which guides cost-effective experimentation and uses interpretable logic programs to encode a state-of-the-art GEM of a model bacterial organism. Notably, [Formula: see text] successfully learned the interaction between a gene pair with fewer training examples than random experimentation, overcoming the increase in experimental design space. [Formula: see text] enables rapid optimisation of metabolic models to reliably engineer biological systems for producing useful compounds. It offers a realistic approach to creating a self-driving lab for biological discovery, which would then facilitate microbial engineering for practical applications.

Active learning↗
PubMed1992

Correlation of calcineurin phosphatase activity and programmed cell death in murine T cell hybridomas.

Ligation of T cell receptor/CD3 complexes induces programmed cell death, or apoptosis, in immature thymocytes and many T cell hybridomas. While it has been demonstrated that T cell receptor-mediated apoptosis requires an increase in intracellular calcium concentration, the specific calcium-dependent signalling events leading to cell death are poorly defined. We have previously shown that T cell receptor/CD3-mediated induction of apoptosis in a murine T cell hybridoma is inhibited by the immunosuppressive drugs cyclosporin A (CsA) and FK506. Recently, it has been determined that these agents inhibit the activity of calcineurin, a calcium- and calmodulin-dependent serine/threonine phosphatase. Using an assay which measures calcineurin activity in cell lysates, we find that calcineurin-dependent dephosphorylation of a phosphopeptide substrate is potently inhibited in hybridomas treated with CsA or FK506. Drug dose-response analyses indicate that the level of cellular calcineurin activity correlates closely with the ability of these cells to undergo apoptosis. Thus, calcineurin appears to be a critical mediator of T cell receptor/CD3 signalling leading to programmed cell death in T cell hybridomas.

Amino Acid Sequence↗
PubMed1992

The effect of graded activity on patients with subacute low back pain: a randomized prospective clinical study with an operant-conditioning behavioral approach.

The aim of this study was to determine whether graded activity restored occupational function in industrial blue-collar workers who were sick-listed for 8 weeks because of subacute, nonspecific, mechanical low back pain (LBP). Patients with LBP, who had been examined by an orthopedic surgeon and a social worker, were randomly assigned to either an activity group (n = 51) or a control group (n = 52). Patients with defined orthopedic, medical, or psychiatric diagnoses were excluded before randomization. The graded activity program consisted of four parts: (1) measurements of functional capacity; (2) a work-place visit; (3) back school education; and (4) an individual, submaximal, gradually increased exercise program, with an operant-conditioning behavioral approach, based on the results of the tests and the demands of the patient's work. Records of the amount of sick leave taken over a 3-year period (ie, the 1-year periods before, during, and after intervention) were obtained from each patient's Social Insurance Office. The patients in the activity group returned to work significantly earlier than did the patients in the control group. The median number of physical therapist appointments before return to work was 5, and the average number of appointments was 10.7 (SD = 12.3). The average duration of sick leave attributable to LBP during the second follow-up year was 12.1 weeks (SD = 18.4) in the activity group and 19.6 weeks (SD = 20.7) in the control group. Four patients in the control group and 1 patient in the activity group received permanent disability pensions. The graded activity program made the patients occupationally functional again, as measured by return to work and significantly reduced long-term sick leave.

Absenteeism↗
PubMed1975

Evaluation by objectives: A systematic approach to the evaluation of educational programs and activities in dental education.

In response to the need for more effective utilization of resources, many institutions of higher learning are beginning to use corporate management methods. These methods, MBO being the most familiar example, center on the common comprehension at all levels of the goals of the corporation. However, institutions of higher learning uniformly lack a cohesiveness of purpose that extends from the level of president to that of teaching faculty. It is a mistake to assume that institutional educational goals are understood and supported by appropriate educational objectives at the department and program level. The evaluation-by-objective format is a concise graphical way to identify areas of support and confusion. It can be applied at each level of the institution and transmitted upward so that personnel at each administrative level can see the way in which its goals and objectives are perceived at lower levels. The proposed format facilitates grouping of educational objectives into programs, providing a framework for the estimation of effort and of needed resources. Since perceptions of effort and required resources will differ depending upon perspective, important issues will be identified, a most significant benefit of the system. The format leads to the formulation of an action plan, which should be reviewed periodically. The first step toward scientific management in institutions of higher learning must be a clear understanding of institutional and subunit goals, along with a set of education objectives that will accomplish these goals. The evaluation-by-objective format directs itself to exactly that concern.

Education, Dental↗