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PubMedDate not supplied

[Modification to the erythrocyte membrane lipids in patients with cardiovascular pathology during balneotherapy].

Erythrocyte phospholipids (FL) composition and their elements polyunsaturated fatty acids of omega-6 and omega-3 type were studied in the course of combined balneotherapy of neurocirculatory dystonia and ischemic heart disease (IHD) patients. The balneological factors promoted FL concentration normalization under positive dynamics in clinical symptoms in 62% of patients with neurocirculatory dystonia. The modulating effect occurred in IHD only in those patients who, in addition to balneotherapy, took alimentary omega-3 fatty acids made of sea products as food additives. The intensity of the FL and fatty acid modification to the end of the treatment was related to the severity of the baseline metabolic abnormalities.

Adolescent↗
PubMed2002

Teaching public health related to the elderly.

It has become axiomatic that the world is aging, not just in the developed countries, but in the less developed regions as well. In 1992 the global elderly population (age 65+) was estimated to be almost 350,000,000 persons, or more than 6% of the world total. During that year the net balance of the world's elderly grew by more than 800,000 persons each month. Projections to the year 2010 indicate that the net monthly gain will rise to more than 1.1 million elderly people. In the early 1990s, 26 countries had more than 2,000,000 elderly persons. The projections suggest that this number could increase to more than 50 nations by the year 2025. And this increase in number of elderly leads to an absolute rise in problems of age-related diseases, such as Alzheimer's disease, cardiovascular disease, stroke, and osteoporosis (with related falls and fractures). At the same time, there is a school of thought that emphasizes the elderly are living longer and healthier lives through better awareness of healthy nutrition, exercise, and other lifestyle factors, as well as improving access to modern medical care that is itself more effective than in previous decades. While the public health practitioner will not be called upon to treat individuals with these pathologies, it is important to know something about them in order to understand their effect on health care systems and to help plan for preventive and health promotion programmes. The preparation of the public health person requires an understanding of these issues and thus some tools for program development for primary, secondary, and tertiary prevention for this high-risk group.

Aged↗
PubMed2003

Partnering with the 21st century workplace: leveraging workplace ecology.

The 'accessible' job market of the 1990's has given way to a challenging job market in a climate of economic uncertainty in the early Twenty-First Century. For vocational rehabilitation professionals this change requires the strategic use of workplace supports to increase the value and sustainability of work performed by people with disabilities in competitive jobs. An analytical framework for leveraging the natural supports of the workplace is provided by the workplace ecology as a bounded environment in which relationships between workers and supervisors promote learning and enhanced performance. The dynamics of the workplace ecology are explored with particular reference to workers with disabilities receiving supported employment services. Recommendations are made for leveraging the workplace ecology to the benefit of the supported worker. Implications for supported employment services in the new millennium are discussed.

Persons with Disabilities↗
PubMedDate not supplied

Relocation stress in adolescents: helping teenagers cope with a moving dilemma.

Relocation affects approximately 20% of the people in the United States. The review of literature indicates that adolescents, already in a vulnerable developmental stage, are particularly susceptible to many stressors related to relocation. These stressors impact on the adolescents' physical welfare, social/peer relationships, school performance, emotionality, and coping behaviors. School professionals can collaborate with psychiatric mental health nurse consultants to help facilitate the adolescents' positive coping with relocation. A health-promotion model to use when working with these adolescents is illustrated.

Adaptation, Psychological↗
PubMed1990

Actin architecture of cultured human thyroid cancer cells: predictor of differentiation?

The actin cytoskeleton is important for cell structure and motility. A disordered actin architecture has been correlated with a high metastatic potential in melanoma, fibrosarcoma, and colon cancer models. Thyrotropin is known to induce growth and differentiation in cultured thyroid cells, whereas the carcinogenic phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) causes dedifferentiation and malignant transformation in many cell lines. We therefore assessed the effect of thyrotropin and TPA on the actin architecture of FTC-133 human follicular thyroid cancer cells in continuous culture. Staining of filamentous actin with rhodamine phalloidin showed that 1 mU/ml or 30 mU/ml thyrotropin-induced actin polymerization was detectable at 1 hour but more notable at 24 hours. Similarly TPA (0.008 to 10 mumol/L) caused rapid actin fiber disruption and redistribution to the cell periphery. Secondary antibody staining for alpha-actinin, a protein that binds and crosslinks actin, was more prominent after treatment with thyrotropin but decreased after TPA. These findings indicate that the actin cytoskeleton has a dynamic response to trophic factors. Thyrotropin promoted actin polymerization, but TPA caused depolymerization. These effects may correlate with cellular alpha-actinin levels. Actin architecture may therefore reflect the state of differentiation of thyroid tumor cells.

Actin Cytoskeleton↗
PubMed1983

The causes and costs of promotion trauma.

Minimizing the stress that nurses experience after a promotion requires an understanding of the dynamics of fledgling managers. Middle roles such as theirs are inherently difficult. We need to be aware of what can happen in moving up the ladder--factors such as loneliness, other unmet needs and unclear job descriptions evoke unique stresses. Knowing these factors, nursing administrators can plan their programs to better support their managers in transition.

Career Mobility↗
PubMed1995

[External fixation in fractures of the lower limb in children].

PURPOSE OF THE STUDY: The indications, morbidity and results of the use of external fixation for fractures of the lower limbs in children is presented. MATERIAL AND METHOD: We studied 72 fractures of the lower limbs (femur: 25; tibia: 47) in 63 children over a seventeen year period. Average age at fracture was 10 yrs 6 mos. (range 4 yrs 5 mos to 14 yrs 6 mos). Forty fractures were open fractures. The indication for external fixation was decided in three different situations: 39 isolated fractures, 11 patients with multiple fractures, and 13 polytraumatized patients. Three different devices were used: Illizarov: 4, Judet: 16, Orthofix: 52. The fixators were left in place until fracture union was demonstrable. RESULTS: Final results were classed into three groups: good, good following reoperation and sequelae. Comparison of the three different series was made using Student's T test. 9 axial deviations or malrotations occurred: 6 times correction was possible with the device in place. Three cases of osteomyelitis occurred at the fracture site. 23 pin tract infections occurred (23 per cent) 5 of which were persistent and 4 required reoperation. The average healing time was different in the three groups: 4.5 mos for isolated fractures: 8.1 mos for multiple fractures and 5.7 mos for polytraumatized patients. Reoperation was required for 4 patients: 2 bone grafts, 1 decortication, 1 bone transport. Ten refractures occurred following removal of the device, 8 times in patients presenting multiple injuries. In 46 patients with a follow-up greater than 18 months, 9 presented an overgrowth between 1 and 2 cm. Following an average follow-up of 2 years 4 months, 7 patients presented sequelae, 56 had good results, 18 following reoperation. DISCUSSION: The use of external fixation remains an irreplaceable method for osteosynthesis of open fractures with severe soft tissue injuries, multiple fractures or in the polytraumatized patient. Some disadvantages such as pin tract infections and refracture following device removal should be taken into consideration before using it for the treatment of simple, isolated closed fractures of the lower limbs in children. CONCLUSION: When external fixation is chosen for treating fractures, it is preferable to use a modular device which allows axial corrections. Local pin site care is essential to prevent early infection. Early weight bearing and dynamization as soon as possible will promote callus mineralization, removal of the device must be progressive and cast protection is recommended.

Adolescent↗
PubMedDate not supplied

[Dynamic electrocardiographic study of a group of urban bus drivers].

On the initiative of Preventive Medicine promoted by the Genoa Urban Transport Company, authors carried out an inquiry of dynamic electrocardiography by Holter during the normal working activity of a group of 95 drivers. It was observed mean value of heart rate of 86.23 +/- 10.08; moreover patients with more working seniority shown a lesser increase of the pulse rate with statistical difference as compared with other groups. In any case we don't observe any change of ventricular repolarization.

Adult↗
PubMed2002

Role of stathmin in the regulation of the mitotic spindle: potential applications in cancer therapy.

Stathmin is a member of a novel class of microtubule-destabilizing proteins that regulate the dynamics of microtubule polymerization and depolymerization. Stathmin promotes microtubule depolymerization during interphase and late mitosis. This microtubule depolymerizing activity of stathmin is regulated by changes in its level of phosphorylation that occur during cell cycle progression. These modifications allow it to play a critical role in the regulation of the dynamic equilibrium of microtubules during different phases of the cell cycle. Stathmin is expressed at high levels in a wide variety of human cancers. Inhibition of stathmin expression in malignant cells interferes with their orderly progression through the cell cycle and abrogates their transformed phenotype. Thus, stathmin provides an attractive molecular target for disrupting the mitotic apparatus and arresting the growth of malignant cells. In this review, we describe the current understanding of the role of stathmin in the regulation of the mitotic spindle and discuss its potential as a therapeutic target of cancer therapy.

Cell Cycle↗
PubMed2005

PI(4,5)P2-dependent microdomain assemblies capture microtubules to promote and control leading edge motility.

The lipid second messenger PI(4,5)P(2) modulates actin dynamics, and its local accumulation at plasmalemmal microdomains (rafts) might mediate regulation of protrusive motility. However, how PI(4,5)P(2)-rich rafts regulate surface motility is not well understood. Here, we show that upon signals promoting cell surface motility, PI(4,5)P(2) directs the assembly of dynamic raft-rich plasmalemmal patches, which promote and sustain protrusive motility. The accumulation of PI(4,5)P(2) at rafts, together with Cdc42, promotes patch assembly through N-WASP. The patches exhibit locally regulated PI(4,5)P(2) turnover and reduced diffusion-mediated exchange with their environment. Patches capture microtubules (MTs) through patch IQGAP1, to stabilize MTs at the leading edge. Captured MTs in turn deliver PKA to patches to promote patch clustering through further PI(4,5)P(2) accumulation in response to cAMP. Patch clustering restricts, spatially confines, and polarizes protrusive motility. Thus, PI(4,5)P(2)-dependent raft-rich patches enhance local signaling for motility, and their assembly into clusters is regulated through captured MTs and PKA, coupling local regulation of motility to cell polarity, and organization.

Animals↗
PubMed2001

Dynamics of Fos-Jun-NFAT1 complexes.

Transcription initiation in eukaryotes is controlled by nucleoprotein complexes formed through cooperative interactions among multiple transcription regulatory proteins. These complexes may be assembled via stochastic collisions or defined pathways. We investigated the dynamics of Fos-Jun-NFAT1 complexes by using a multicolor fluorescence resonance energy transfer assay. Fos-Jun heterodimers can bind to AP-1 sites in two opposite orientations, only one of which is populated in mature Fos-Jun-NFAT1 complexes. We studied the reversal of Fos-Jun binding orientation in response to NFAT1 by measuring the efficiencies of energy transfer from donor fluorophores linked to opposite ends of an oligonucleotide to an acceptor fluorophore linked to one subunit of the heterodimer. The reorientation of Fos-Jun by NFAT1 was not inhibited by competitor oligonucleotides or heterodimers. The rate of Fos-Jun reorientation was faster than the rate of heterodimer dissociation at some binding sites. The facilitated reorientation of Fos-Jun heterodimers therefore can enhance the efficiency of Fos-Jun-NFAT1 complex formation. We also examined the influence of the preferred orientation of Fos-Jun binding on the stability and transcriptional activity of Fos-Jun-NFAT1 complexes. Complexes formed at sites where Fos-Jun favored the same binding orientation in the presence and absence of NFAT1 exhibited an 8-fold slower dissociation rate than complexes formed at sites where Fos-Jun favored the opposite binding orientation. Fos-Jun-NFAT1 complexes also exhibited greater transcription activation at promoter elements that favored the same orientation of Fos-Jun binding in the presence and absence of NFAT1. Thus, the orientation of heterodimer binding can influence both the dynamics and promoter selectivity of multiprotein transcription regulatory complexes.

Allosteric Regulation↗
PubMed2003

Distinct promoter regions regulate spatial and temporal expression of the Drosophila caspase dronc.

DRONC is an apical Drosophila caspase essential for programmed cell death during fly development. During metamorphosis, dronc gene expression is regulated by the steroid hormone ecdysone, which also regulates the levels of a number of other critical cell death proteins. As DRONC protein levels are important in determining caspase activation and initiation of cell death, we have analyzed the regulation of the dronc promoter using transgenic flies expressing a LacZ reporter gene under the control of the dronc promoter. Our results indicate that dronc expression is highly dynamic during Drosophila development, and is controlled both spatially and temporally. We demonstrate that while a 2.3 kb dronc promoter region contains most of the information required for correct gene expression, a 1.1 kb promoter region is expressed in some tissues and not others. We further demonstrate that during larval-pupal metamorphosis, two ecdysone-induced transcription factors, Broad-Complex and E93, are required for correct dronc expression. Our data suggest that the dronc promoter is regulated in a highly complex manner, and provides an ideal system to explore the temporal and spatial regulation of gene expression driven by nuclear hormone receptors.

Animals↗
PubMed2002

Mutagenesis of prochlorothrix plastocyanin reveals additional features in photosystem I interactions.

Three surface residues of plastocyanin from Prochlorothrix hollandica have been modified by site-directed mutagenesis. Changes have been made in methionine 33, located in the hydrophobic patch of the copper protein, and in arginine 86 and proline 53, both located in the eastern hydrophilic area. The reactivity toward photosystem I of single mutants M33N, P53A, P53E, R86Q, R86E, and the double mutant M33N/P14L has been studied by laser flash absorption spectroscopy. All the mutations yield increased reactivity of plastocyanin toward photosystem I as compared with wild type plastocyanin, thus indicating that in Prochlorothrix electron donation to photosystem I is not optimized. The most drastic increases in the intracomplex electron transfer rate are obtained with mutants in methionine 33, whereas replacing arginine 86 only modestly affects the plastocyanin-photosystem I equilibrium constant for complex formation. Mutations at position 53 also promote major changes in the association of plastocyanin with photosystem I, yielding a change from a mechanism involving complex formation to a simpler collisional interaction. Molecular dynamics calculations indicate that mutations at position 33 promote changes in the H-bond network around the copper center. The comparative kinetic analysis of the reactivity of Prochlorothrix plastocyanin mutants toward photosystem I from other cyanobacteria reveals that mutations M33N, P53A, and P53E result in enhanced general reactivity.

Base Sequence↗
PubMed2003

Membrane dynamics, cholesterol homeostasis, and Alzheimer's disease.

Alzheimer's disease (AD) is characterized by the deposition of beta-amyloid (A beta) plaques derived from the amyloidogenic processing; of a transmembrane protein called beta-amyloid precursor protein (APP). In addition to the known genetic/sporadic factors that promote the formation of A beta, the composition and structural dynamics of the membrane are also thought to play a significant role in the amyloidogenic processing of APP that promotes seeding of A beta. This minireview reinforces the roles played by membrane dynamics, membrane microdomains, and cholesterol homeostasis in relation to amyloidogenesis, and reviews current strategies of lowering cholesterol in treating AD.

Alzheimer Disease↗
PubMed2026

Epigenetic Repression of TP53 Transcription Underlies Cancer Cell Persistence for Carboplatin Resistance in Non-Small Cell Lung Cancer.

While chemoresistance in non-small cell lung cancer (NSCLC) cells has historically been attributed to permanent genetic mutations, emerging evidence highlights the role of nongenetic transcriptional plasticity and 'drug-tolerant persister' cells. To systematically map these epigenetic vulnerabilities, we utilized a genome-wide CRISPR interference library to screen wild-type TP53 NSCLC (A549) cells under carboplatin selection. Using the DrugZ algorithm and subsequent pathway enrichment analyses, this screen revealed that transcriptional suppression of interstrand crosslink DNA repair networks, including the Fanconi anemia pathway, markedly sensitized cells to carboplatin. Unexpectedly, transcriptional silencing of TP53 and its downstream target CDKN1A emerged as the strongest drivers of resistance, enabling cells to bypass therapy-induced senescence and maintain their proliferative potential later. To validate these findings in a clinically relevant context, we established a chronic carboplatin-resistant cell model (A549CarboR cells). A549CarboR exhibited a reduction in TP53 transcripts, along with decreased H3K27 acetylation and increased DNA hypermethylation on its promoter. Epigenetic remodeling using the DNA methyltransferase inhibitor (DNMTi) was associated with unblocking TP53 transcription, restored p53 signaling, and resensitization of resistant cells to carboplatin. Conversely, histone deacetylase inhibitors induced CDKN1A transcription to bypass TP53, indicating distinct epigenetic circuits. Collectively, the results demonstrate for the first time that TP53 expression is dynamically regulated at the transcriptional level through promoter methylation related to the drug tolerance. These insights emphasize that epigenetic silencing, rather than exclusive genetic loss-of-function, contribute to platinum resistance and underscore the therapeutic potential of pairing platinum regimens with DNMTi to target the transcriptomic plasticity of persistent cancer cell populations.

CRISPR interference screening↗
PubMed2005

Computational simulation of axial dynamization on long bone fractures.

BACKGROUND: Axial dynamization has been shown in previous studies to promote callus formation, improve bone healing at fracture sites, and enhance bone remodeling. However, the possibility of non-axial movements or uniform fracture site compression during dynamization, and the appropriate relaxation of fixator joints to achieve such function, have not been investigated. METHODS: This study used previously developed computational models based on two commercially available unilateral external fixators (Dynafix and Orthofix) to analyze the fixator joint adjustments used and the fracture site movements generated during dynamization. FINDINGS: When none of the fixator's sliding joints were parallel to the long bone axis, significant non-axial movements occurred during dynamization. The dual sliding joint design of the Dynafix fixator was beneficial in reducing these non-axial movements. When all of the fixator joints were allowed to adjust simultaneously during dynamization, exact axial movement or uniform compression at a complicated fracture site was achievable. INTERPRETATION: This study revealed that significant non-axial movements may occur during dynamization, and that such a deficiency can be corrected by relaxing certain fixator joints in addition to the sliding mechanism. The same modeling technique can also be applied in bone lengthening application to assure desirable limb alignment during the distraction process. These analysis results can aid the performance assessment of an external fixator and facilitate appropriate application of such a device to achieve either active or controlled axial movement.

Computer Simulation↗
PubMed2000

Intermediate state during the crystal transition in aspartame, studied with thermal analysis, solid-state NMR, and molecular dynamics simulation.

Aspartame (L-alpha-aspartyl-L-phenylalanine methyl ester) is a dipeptide sweetener about 200 times as sweet as sugar. It exists in crystal forms such as IA, IB, IIA, and IIB, which differ in crystal structure and in the degree of hydration. Among these, IIA is the most stable crystal form, and its crystal structure has been well determined (Hatada et al., J. Am. Chem. Soc., 107, 4279-4282 (1985)). To elucidate the structural factors of thermal stability in the IIA form of aspartame and to examine the physical process in the crystal transformation between the IIA and IIB forms, we performed a thermal analysis and solid-state NMR measurements. We found that a quasi-stable intermediate state exists in the transformation, and it has the same crystal lattice as the usual IIA form, despite the dehydration from 1/2 mol to 1/3 mol per 1 mol of aspartame. The results of the energy component analysis and the molecular dynamics simulation suggest that the entropic effect promotes the generation of the intermediate state, which is presumably caused by the evaporation of the water of crystallization and the increase of molecular motion in aspartame. Thus, the thermal stability of the IIA form is attributable to a structural property, i.e., the crystal lattice itself is retained during the above dehydration. Moreover, the molecular dynamics simulations suggest that the aspartame molecules have two kinds of conformational flexibility in the intermediate state.

Aspartame↗