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Results for “Promoter dynamics”

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At least 937 records · Page 52Linked to original sources
PubMed2006

Single-cell analysis of glucocorticoid receptor action reveals that stochastic post-chromatin association mechanisms regulate ligand-specific transcription.

The glucocorticoid receptor (GR) dynamically interacts with response elements in the mouse mammary tumor virus (MMTV) promoter to regulate steroid-dependent transcription. In a clonal mammary carcinoma cell line containing a tandem array of MMTV promoter-reporter gene cassettes integrated at a single genomic locus, direct binding of a green fluorescent protein (GFP)-GR fusion protein to the MMTV regulatory elements can be observed in living cells. After ligand treatment, MMTV-dependent transcription in individual cells was detected by RNA fluorescence in situ hybridization (FISH). High-resolution fluorescence images were acquired from large numbers of randomly selected cells. Images were analyzed with a novel automated computer algorithm, measuring the RNA FISH signal and the relative GFP-GR fluorescence intensity at the MMTV array for each cell. Although dexamethasone increased the mean RNA FISH signal approximately 10-fold, RU486 produced only about a 2-fold induction, as expected for this mixed antagonist. For all treatment conditions, the relative GFP-GR fluorescence at the array for the averaged cells paralleled the RNA FISH measurements, suggesting that image analysis accurately detected an increase in steady-state GR association with the MMTV array that was responsible for the increase in transcriptional activity. The antagonist-dependent decreases in GR association with the MMTV promoter were confirmed by chromatin immunoprecipitation experiments, supporting the image analysis results. A pronounced cell-to-cell variability was observed in RNA FISH signal and GR-MMTV association within treatment groups. We observed a nonlinear relationship between GR-MMTV association and RNA FISH in individual cells, indicating that differences in GR-MMTV interaction account for some, but not all, of the transcriptional heterogeneity between individual cells. In selected cell subpopulations with equal levels of GR-MMTV association, there was a decrease in RNA FISH signal with RU486 treatment compared with dexamethasone treatment. These results indicate that stochastic events occurring after GR-promoter association, such as the actions of chromatin remodeling complexes or other cofactors, change in a ligand-dependent manner and regulate heterogeneous transcription in individual cells.

Animals↗
PubMed1990

Conformational study of the cembranoid sarcophytol A, a potent anti-tumor-promoter.

Conformational analysis of the marine cembranoid sarcophytol A (1a), a potent anti-tumor promoter, was carried out using a newly introduced molecular mechanic and molecular dynamic program Discover. Four minimum-energy conformations were derived, in accordance with a previous results of the epoxidation of 1a, which afforded 7R,8R/7S,8S- and 11R,12R/11S,12S-epoxide pairs. The most stable conformation was the one having C-19 and C-20 directed opposite to C-18, with respect to the average plane of the fourteen-membered ring. X-Ray crystallography of sarcophytol A alpha-methoxy-alpha-trifluoromethylphenylacetate (1c) was carried out simultaneously. This confirmed the 14S absolute configuration of 1a but the conformation of crystalline 1c did not correspond to any of the four minimum-energy conformers of 1a.

Crystallization↗
PubMed2002

The fault lines of academic medicine.

Unprecedented advances in biomedical research and the upheaval in health care economics have converged to cause seismic changes in the traditional organization of medical schools and academic health centers. This process is particularly evident in departments of internal medicine. The activities and functions of academic medicine are in the midst of separation and realignment along lines that do not honor historical departmental and divisional boundaries. The organization of a successful medical school or department must be dynamic, constantly serving its constituents to accommodate progress and change and to promote optimal structure for academic productivity.

Academic Medical Centers↗
PubMed2003

[Aging with dependence: family needs and responsibilities].

This article highlights the phenomenon of "aging with dependence" as a challenge to be dealt with by the field of collective health and discusses responsibilities for providing health care to this population contingent, comparing the necessary and existing conditions for families to assume responsibility for such care. The analysis is based on authors and theoretical references involving studies on aging, dependence, public policies, and available community resources for health care for the elderly. The following themes are emphasized: dependence and aging, the economic issue of dependence, family care, and family needs. The article concludes that since dependence is a dynamic process, it should be approached through programs that range from health promotion strategies to the establishment of support networks for long-term care in the community. These programs should be part of a public policy that involves all sectors of society and that can provide back-up for dependent seniors, with or without family support.

Activities of Daily Living↗
PubMed1991

AIDS in Thailand.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗
PubMed2000

How to set the ventilator in asthma.

All patients with bronchial asthma are at risk of developing severe episodes of airway narrowing that do not respond to the usual medical treatment, a life-threatening situation referred to as status asthmaticus. In some cases, ventilatory failure occurs, necessitating mechanical ventilation to support gas exchange and to unload the respiratory muscles, giving time for other therapeutic interventions to improve the functional status of the patient. Mechanical ventilatory support poses additional risks to the patients, due to interaction between the pathophysiology of the disease and the process of mechanical ventilation. Dynamic hyperinflation, a cardinal feature of the pathophysiology, may cause serious complications during mechanical ventilation. Setting the ventilator, such as to minimize the dynamic hyperinflation, is a key point in the management of mechanically ventilated patients with status asthmaticus. Strategies to reduce dynamic hyperinflation, such as hypoventilation (permissive hypercapnia), increase of expiratory time and promotion of patient-ventilator synchrony are mandatory and significantly decrease the morbidity and mortality of the disease. Continuous monitoring of the effectiveness of these strategies, as well as the functional status of the patient, is crucial in order to limit complications associated with mechanical ventilation and to identify the time that weaning can start.

Functional Residual Capacity↗
PubMed1999

[Health survey: a brief reflexion on individual and public health].

This article is a brief literature review that aims to stimulate reflections about individual and collective health concepts, especially approaching some authors which indicate to new health interventions nowadays. It features procedural and historical health aspects with the perspective of new orientations to follow its dynamism and complexity. It also refers to recommendations of international events to promote health in the 21st century.

Brazil↗
PubMed2000

Trimetazidine and the contractile response of dysfunctional myocardium in ischaemic cardiomyopathy.

BACKGROUND: The therapeutic effect of anti-ischemic compounds is related to their ability to improve the oxygen supply-demand balance of the ischemic myocardium by increasing myocardial blood flow (calcium-antagonists), by reducing regional myocardial oxygen consumption (verapamil, betablockers) and increasing peripheral pooling of blood (nitrates, nifedipine). All these actions are also accompanied by hemodynamic changes, as evidenced by a lower double product, reduced wall stress, lower pulmonary wedge pressure, and lower systemic arterial pressure. In general, it was found that the combination of a betablocker with nifedipine improved the antianginal effect by further reducing the number and duration of ischemic events. The combination of a nitrate with a beta-blocker is particularly useful because it reduces the risk of heart failure by lowering left ventricular end-diastolic pressure and volume and by attenuating the negative inotropic effect of the betablocker. Although a combination therapy demonstrated benefits in comparison with drug treatment alone, it is associated with a higher incidence of untoward events. Trimetazidine (2, 3, 4 trimethoxybenzyl-piperazine dihydrochloride) is a novel anti-ischemic compound with a peculiar mechanism of action. Its anti-ischemic properties are unrelated to changes in myocardial oxygen supply-to-demand ratio, as shown by no significant effects on heart rate, blood pressure or rate-pressure product both at rest and during dynamic exercise. There are several possible mechanisms of action by which trimetazidine promotes preservation of membrane structures and cellular function: limitation of intracellular acidosis, correction of disturbances of transmembrane ion exchange leading to calcium overload, prevention of an excessive production of free radicals, inhibition of the inflammatory reaction and an antiplatelet effect. These documented actions cooperate to increase the rate of resynthesis of high-energy phosphates within myocardial cells after episodes of ischemia. In several trials, trimetazidine has been tested as an antianginal agent, both as monotherapy and combined with "classical" anti-ischemic compounds. In comparison with nifedipine, trimetazidine had similar efficacy in reducing the number of weekly anginal attacks and in increasing the ischemic threshold in a group of 39 patients with stable angina. However, the incidence of side effects was significantly higher with nifedipine (5 vs 20), and affected 5 patients with trimetazidine and 13 patients with nifedipine (p = 0.03). In a relatively large European study involving 149 patients (Trimetazidine European Multicenter Study, TEMS), trimetazidine (20 mg t.i.d.) was compared with propranolol (40 mg t.i.d.) in patients with stable angina pectoris and documented significant coronary artery stenoses. The number of anginal attacks was reduced equally by both drugs and exercise duration was increased by both treatments. However, in contrast with propranolol trimetazidine did not alter the rate pressure product. In patients already treated with nifedipine or beta-blockers, the addition of trimetazidine (20 mg t.i.d.) was able to reduce the number and the duration of anginal attacks and improved also the exercise capacity. Trimetazidine is generally well tolerated and only minor side effects have been reported (drowsiness, sedation, diarrhea). The improvement in cardiac energy metabolism should theoretically translate into enhancement in mechanical efficiency. This hypothesis has been object of recent investigations in patients with ischemic heart disease with and without left ventricular dysfunction. Brottier, et al. demonstrated that patients with ischemic cardiomyopathy treated with trimetazidine had a higher ejection fraction (measured by radionuclide angiography) than control patients who received a placebo after 6 months of therapy (p < 0.018). The group of Chierchia demonstrated that trimetazidine improved ischemic regional myocardial dysfunction at rest and during stress-induced ischemia in 15 patients with chronic coronary artery disease without affecting the hemodynamic determinants of myocardial oxygen consumption. There is recent demonstration that trimetazidine improves the contractile response of left ventricular hibernating myocardium in patients with ischemic heart disease. Belardinelli et al. showed that trimetazidine improved the contractile response of dysfunctional myocardial to low-dose dobutamine in patients with ischemic heart disease and left ventricular function. Twenty-two patients with prior anterior myocardial infarction and injection fraction < 35% (33 +/- 7%) were randomized into 2 groups. A group (= 11) received trimetazidine (20 mg tid) for 2 months, while another group (= 11) received a placebo. The usual medications were not altered during the study. (ABSTRACT TRUNCATED)

Humans↗
PubMedDate not supplied

[Population aging and public health. The active aging concept].

Population aging has been recognized as one of the most important human achievement, being the result of improved living conditions and medical advances. According to UN Projections, in the year 2025 there will be living in the world 1.2 billion elderly people, and 71 % of them are likely to be in the developing countries. Between 1950 and 2025, the "Old" Old (those who are 80 years and above) will grow twice as fast as the 60-plus age group. In these conditions, we are confronted with two major issues: providing older people with opportunities for independence, health, productivity, and protection while at the same time maintaining economic prosperity in society. These two issues will require multiple economic, financial and social changes. The concept of quality of life is expressed in this large chapter about aging through active aging, which is depending on social and economic factors, personal and behavioural factors, health and social services, environment, gender and culture. The programmes for promoting active aging have to encourage healthy life styles, including healthy nutrition policies, active life and avoidance of chronic illnesses.

Aged↗
PubMed2006

Diabetes mellitus patients' family caregivers' subjective quality of life.

OBJECTIVES: To assess the subjective quality of life (QOL) of family caregivers of Sudanese type-1 and type-2 diabetic outpatients, using the WHO 26-item QOL instrument, compared with a general population sample; and to examine the factors associated with caregiver QOL. METHOD: Responses of caregivers of 105 outpatients with type-1 diabetes and 135 with type-2 diabetes were compared with 139 general population subjects. RESULTS: Caregivers were satisfied with the content of items related to general social supports. Type-1 caregivers had significantly lower QOL scores than type-2 caregivers and the general population. Parents and siblings had lowest scores compared with other family groups. Caregivers scored higher than patients. Patients' age and duration of illness, and caregivers' education, marital status and state of health were positively associated with caregiver QOL. Caregivers' QOL was predicted by their appraisal of patients' QOL. CONCLUSIONS: Caregivers who were sick, younger, single, less educated and caring for patients with more recent illness appeared relatively vulnerable. Clinicians should be interested in the dynamics of the family caregiving situation--as it impacts QOL--and in promoting caregiver awareness of diabetes in order to enhance the caregiving role, quality of care and QOL.

Adult↗
PubMed1996

The patients' library movement: an overview of early efforts in the United States to establish organized libraries for hospital patients.

The patients' library movement in the United States, a dynamic, cohesive drive begun and sustained by librarians and physicians, strove to promote placement of organized libraries for patients in hospitals. It took shape in the early years of this century, evolving from its proponents' deeply held conviction that books and reading foster the rehabilitation of sick people. The American Library Association's World War I service to hospitalized military personnel dramatically reinforced the conviction; the post-World War I institution of public library extension services to general hospitals explicitly reflected it. Enormous energy was infused into the patients' library movement. Throughout the first half of this century, there were sustained efforts not only to establish organized libraries for hospitalized people but also to expand and systematically study bibliotherapy and to shape patients' librarianship as a professional specialty. The movement's achievements include the establishment of patients' library committees within national and international associations; impetus for development of academic programs to train patients' librarians; and publication, from 1944 through 1970, of successive sets of standards for hospital patients' libraries. The first of these remain the first standards written and issued by a professional library association for a hospital library.

History, 20th Century↗
PubMed2006

Nutrient modulation of intestinal gas dynamics in healthy humans: dependence on caloric content and meal consistency.

The actions of nutrients on gut transit of liquids and solids have been extensively studied, but the effects of meal ingestion on intestinal gas flow are unexplored. We hypothesized that meals of varying caloric content and consistency modulate gas transit to different degrees. Nine healthy volunteers underwent jejunal perfusion of physiological gas mixtures at 12 ml.min(-1).3 h, with ingestion of nothing (control), water (240 ml), 240-kcal liquid meals, and 240-kcal solid meals at the end of the second hour in separate studies. Gas was quantified from an intrarectal catheter. After an initial lag phase, gas evacuation approached steady state by the end of the fasting period. Solid and liquid caloric meals increased total gas volumes evacuated from 5-40 min after ingestion vs. control studies (P < 0.05). These increases resulted from increased numbers of bolus gas evacuations (P < 0.05), whereas bolus volumes, pressures, and flow rates were similar for all test conditions. Solid and liquid caloric meals elicited similar effects on bolus gas dynamic parameters, whereas water did not affect these measures vs. control (NS, not significant). Both caloric meals and the noncaloric liquid meal increased continuous gas flow, which represented <2% of total gas expulsion. In conclusion, caloric meals promote bolus gas transit in healthy humans, whereas noncaloric liquids have no effect. Solids stimulate early postprandial gas dynamics to the same extent as liquid meals of similar caloric content. Thus modulatory effects of meals on intestinal gas transit depend on their caloric content but not their consistency.

Adaptation, Physiological↗
PubMed2001

Cortactin promotes and stabilizes Arp2/3-induced actin filament network formation.

Cortactin is a c-src substrate associated with sites of dynamic actin assembly at the leading edge of migrating cells. We previously showed that cortactin binds to Arp2/3 complex, the essential molecular machine for nucleating actin filament assembly. In this study, we demonstrate that cortactin activates Arp2/3 complex based on direct visualization of filament networks and pyrene actin assays. Strikingly, cortactin potently inhibited the debranching of filament networks. When cortactin was added in combination with the active VCA fragment of N-WASp, they synergistically enhanced Arp2/3-induced actin filament branching. The N-terminal acidic and F-actin binding domains of cortactin were both necessary to activate Arp2/3 complex. These results support a model in which cortactin modulates actin filament dendritic nucleation by two mechanisms, (1) direct activation of Arp2/3 complex and (2) stabilization of newly generated filament branch points. By these mechanisms, cortactin may promote the formation and stabilization of the actin network that drives protrusion at the leading edge of migrating cells.

Actin Cytoskeleton↗
PubMed2005

Short-term effects of repetitive arm work and dynamic exercise on glucose metabolism and insulin sensitivity.

AIM: To determine whether repetitive arm work, with a large component of static muscle contraction alters glucose metabolism and insulin sensitivity. METHOD: Euglycemic clamps (2 h) were started in ten healthy individuals 15 min after 37 min periods of: (1) repetitive arm work in a simulated occupational setting; (2) dynamic concentric exercise on a cycle ergometer at 60% of VO(2max) and (3) a resting regime as a control. During the experimental periods, blood samples were collected, blood pressure was measured repeatedly and electrocardiogram (ECG) was recorded continuously. During the clamps, euglycemia was maintained at 5 mmol l(-1) and insulin was infused at 56 mU m(-2) min(-1) for 120 min. RESULTS: The insulin-mediated glucose disposal rate (M-value) for the steady-state period (60-120 min) of the clamp, tended to be lower following arm work than for both cycling and resting regimes. When dividing the steady-state period into 20-min intervals, the insulin sensitivity index (ISI) was significantly lower for arm work compared with the resting control situation between 60-80 min (P = 0.04) and 80-100 min (P = 0.01), respectively. Catecholamines increased significantly for arm work and cycling compared with resting regime. Data from heart rate variability (HRV) measurements indicated significant sympathetic activation during repetitive arm work. CONCLUSION: The results indicate that repetitive arm work might acutely promote insulin resistance, whereas no such effect on insulin resistance was produced by dynamic concentric exercise.

Adult↗
PubMed2004

Mechanisms of coexistence in competitive metacommunities.

Although there is a large body of theory on spatial competitive coexistence, very little of it involves comparative analyses of alternative mechanisms. We thus have limited knowledge of the conditions under which multiple spatial mechanisms can operate or of emergent properties arising from interactions between mechanisms. Here we present a mathematical framework that allows for comparative analysis of spatial coexistence mechanisms. The basis for comparison is mechanisms operating in spatially homogeneous competitive environments (e.g., life-history trade-offs) versus mechanisms operating in spatially heterogeneous competitive environments (e.g., source-sink dynamics). Our comparative approach leads to several new insights about spatial coexistence. First, we show that spatial variation in the expression of a life-history trade-off leads to a unique regional pattern that cannot be predicted by considering trade-offs or source-sink dynamics alone. This result represents an instance where spatial heterogeneity constrains rather than promotes coexistence, and it illustrates the kind of counterintuitive emergent properties that arise due to interactions between different classes of mechanisms. Second, we clarify the role of dispersal mortality in spatial coexistence. Previous studies have shown that coexistence can be constrained or facilitated by dispersal mortality. Our broader analysis distinguishes situations where dispersal mortality is not necessary for coexistence from those where such mortality is essential for coexistence because it preserves spatial variation in the strength of competition. These results form the basis for two important future directions: evolution of life-history traits in spatially heterogeneous environments and elucidation of the cause and effect relationship(s) between biodiversity and ecosystem functioning.

Animals↗
PubMed2004

Structural basis for phosphatidylinositol phosphate kinase type Igamma binding to talin at focal adhesions.

The cytoskeletal protein talin binds to a short C-terminal sequence in phosphatidylinositol phosphate kinase type Igamma (PIPKIgamma), activating the enzyme and promoting the local production of phosphatidylinositol 4,5 bisphosphate, which regulates focal adhesion dynamics as well as clathrin-mediated endocytosis in neuronal cells. Here we show by crystallographic, NMR, and calorimetric analysis that the phosphotyrosine binding (PTB)-like domain of talin engages the PIPKIgamma C terminus in a mode very similar to that of integrin binding. However, PIPKIgamma binds in the canonical PTB-peptide mode with an SPLH motif replacing the classic NPXY motif. The tighter packing of the SPLH motif against the hydrophobic core of talin may explain the stronger binding of PIPKIgamma. Two tyrosine residues flanking the SPLH motif (Tyr-644 and Tyr-649) have been implicated in the regulation of talin binding. We show that phosphorylation at Tyr-644, a Src phosphorylation site in vivo, has little effect on the binding mode or strength, which is consistent with modeling studies in which the phosphotyrosine makes surface-exposed salt bridges, and we suggest that its strong activating effect arises from the release of autoinhibitory restraints in the full-length PIPKIgamma. Modeling studies suggest that phosphorylation of Tyr-649 will likewise have little effect on talin binding, whereas phosphorylation of the SPLH serine is predicted to be strongly disruptive. Our data are consistent with the proposal that Src activity promotes a switch from integrin binding to PIPKIgamma binding that regulates focal adhesion turnover.

Amino Acid Motifs↗