Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “instability”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,261 records · Page 70Linked to original sources

Dynamic axial carpal instability: a case report.

The concept of distal carpal row dissociation is not new. It has occurred secondary to high-energy crush or blast injuries, with resultant axial dislocations of both carpal rows and metacarpals. Axial carpal sprains without disruption or dynamic axial carpal instability have not been previously described. The evaluation of this new type of carpal instability with radiographs, tomography, arthrography, and magnetic resonance imaging failed to demonstrate its etiology. Arthroscopic evaluation of the midcarpal and radiocarpal joints demonstrated a dynamic axial carpal instability with incompetence of the capitohamate and scapholunate ligaments. Stabilization of the axial instability by capitohamate arthrodesis relieved the chronic wrist pain.

Adult↗

A role for chromosomal instability in the development of and selection for radioresistant cell variants.

Chromosome instability is a common occurrence in tumour cells. We examined the hypothesis that the elevated rate of mutation formation in unstable cells can lead to the development of clones of cells that are resistant to the cancer therapy. To test this hypothesis, we compared chromosome instability to radiation sensitivity in 30 independently isolated clones of GM10115 human-hamster hybrid cells. There was a broader distribution of radiosensitivity and a higher mean SF(2)in chromosomally unstable clones. Cytogenetic and DNA double-strand break rejoining assays suggest that sensitivity was a function of DNA repair efficiency. In the unstable population, the more radioresistant clones also had significantly lower plating efficiencies. These observations suggest that chromosome instability in GM10115 cells can lead to the development of cell variants that are more resistant to radiation. In addition, these results suggest that the process of chromosome breakage and recombination that accompanies chromosome instability might provide some selective pressure for more radioresistant variants.

Animals↗

Pathogenesis of upper cervical instability.

SUMMARY. The purpose of this article is to review the pathogenesis of upper cervical instability. Instability can arise from inflammatory, congenital and traumatic causes. The commonest causes of atlanto-axial dislocation are rheumatoid arthritis and Down's syndrome. The review revealed much less information about the relatively minor instabilities that are probably responsible for a number of chronic complaints of the type seen by manual therapists. The potential involvement of passive (ligamentous), active (musculotendinous) and neural control subsystems in maintaining the stability of the spine may go some way to explaining the spectrum of conditions included under the term clinical instability. Copyright 1996 Harcourt Publishers Ltd.

Journal Article↗

Induced genome instability as a potential screening test for cancer susceptibility?

The variety of mutations associated with carcinogenesis, along with variations in penetrance and environmental factors, complicate the genetic screening for cancer predisposition. It is proposed here that the detection of inherent genome instability as determined by increased mutagen susceptibility may enhance the identification of populations at risk for cancer. In support for this hypothesis, our analysis reveals a strong association between mutagen-induced chromosomal instability in peripheral blood lymphocytes and the propensity for cancers of oral cavity, pharynx, larynx, and lung. DNA instability in response to a variety of mutagens identifies patients with gastrointestinal, brain, endocrine, breast, skin, and hematologic tumors as well as individuals with cancer family syndromes. Induced genome instability therefore appears to be strongly linked to cancer predisposition, and prospective studies may yield a screening test utilizing a panel of mutagens to better identify populations at risk.

Chromosomes, Human↗

Instability and falling in elderly patients.

Falls and instability in elderly patients may result from a single disease process or from the accumulated effect of multiple diseases and impairments. Therefore the first step in evaluating an elderly patient with a history of falling or instability is to identify single, potentially treatable diseases, such as normal pressure hydrocephalus, cervical spondylosis, or lumbar stenosis. The next step, regardless of whether or not a single disease process is identified, is to determine all factors possibly contributing to instability. This step involves a careful history and examination using the checklist approach already described. Careful recreation of the fall situation including location, activity engaged in, how the patient was feeling, and any environmental hazards present is an important part of the fall history. Re-creating the fall situation may provide important clues toward etiology as well as prevention. Interventions aimed at ameliorating identified impairments should be considered. Obviously, interventions need to be considered within the context of overall patient health and well-being rather than merely fall prevention. Fall preventive interventions may be medical, surgical, rehabilitative, or educational, or may involve environmental manipulations. Examples include surgery and good lighting for subjects with cataracts, adaptive footwear or surgery for patients with severe foot deformities, or physical therapy, appropriate walking aids, and raised seats for subjects with difficulty or unsteadiness in getting up. Instability and falling are not inevitable accompaniments of aging, but are problems that result from identifiable disabilities and impairments.(ABSTRACT TRUNCATED AT 250 WORDS)

Accidental Falls↗

The sharkskin instability of polymer melt flows.

Flows of polymeric liquids undergo instabilities whose origins are quite different from those of Newtonian flows, due to their elastic character and the complexity of the fluid/solid boundary condition. This article reviews recent studies of one such instability, the sharkskin phenomenon observed during extrusion of many linear polymers. Key experimental observations are summarized; one important fact that has become clear is the importance of the interaction between the molten polymer and the solid walls of the flow channel, especially near the contact line at the exit of the channel. Recent developments in understanding the relationship between wall slip and disentanglement of wall-adsorbed polymers from the bulk flow are briefly described, and putative heuristic mechanisms relating the instability to slip and contact line motion are presented. Finally, we review mathematical analyses of the stability of viscoelastic shear flows with slip boundary conditions. Some recent analyses yield instability predictions that are consistent with experiments, but further work is required to discriminate between the various mechanisms that have been proposed. (c) 1999 American Institute of Physics.

Journal Article↗

Nonlinear instability of elementary stratified flows at large Richardson number.

Elementary stably stratified flows with linear instability at all large Richardson numbers have been introduced recently by the authors [J. Fluid Mech. 376, 319-350 (1998)]. These elementary stratified flows have spatially constant but time varying gradients for velocity and density. Here the nonlinear stability of such flows in two space dimensions is studied through a combination of numerical simulations and theory. The elementary flows that are linearly unstable at large Richardson numbers are purely vortical flows; here it is established that from random initial data, linearized instability spontaneously generates local shears on buoyancy time scales near a specific angle of inclination that nonlinearly saturates into localized regions of strong mixing with density overturning resembling Kelvin-Helmholtz instability. It is also established here that the phase of these unstable waves does not satisfy the dispersion relation of linear gravity waves. The vortical flows are one family of stably stratified flows with uniform shear layers at the other extreme and elementary stably stratified flows with a mixture of vorticity and strain exhibiting behavior between these two extremes. The concept of effective shear is introduced for these general elementary flows; for each large Richardson number there is a critical effective shear with strong nonlinear instability, density overturning, and mixing for elementary flows with effective shear below this critical value. The analysis is facilitated by rewriting the equations for nonlinear perturbations in vorticity-stream form in a mean Lagrangian reference frame. (c) 2000 American Institute of Physics.

Journal Article↗

Oscillatory wetting instability induced by liquid-liquid decomposition in a Ga--Pb alloy.

We present the first experimental investigation and pertinent theoretical modeling of an interfacial oscillatory instability in a binary fluid alloy, the Ga-Pb system. It is characterized by spinodal decomposition at elevated temperatures and by a complete wetting transition at liquid-liquid coexistence. For the alloy Ga(0.95)Pb(0.05) the fluid interface has been probed by second harmonic generation (SHG) under UHV conditions at temperatures between 740 and 550 K. At conditions inside the miscibility gap clear oscillations of the SHG-intensity with a period of approximately 30 min are found for different cooling cycles and also at constant temperatures. These interfacial oscillatory instabilities simultaneously induce temperature oscillations in the bulk fluid with the same period. This phenomenon can be explained by a periodic variation of the fluid interfacial emissivity. A model has been developed which describes the wetting-dewetting dynamics by hydrodynamic equations within the Reynolds approximation. It is found that the interfacial oscillatory instability is determined by capillary-gravitation instability. The model quantitatively describes the time evolution of the interfacial and temperature oscillations and gives the correct value of the oscillation period. A detailed comparison of the experimental and model results is given.

Journal Article↗

Solvent-driven dewetting and rim instability.

An experimental method suitable for reproducible results has been used to investigate dewetting behavior of thin films of solvent-laden polymer. This solvent-driven dewetting enables one to change spreading coefficient by an order of magnitude that is not readily realizable in thermal dewetting and to study polar interactions that have not been fully exploited experimentally. While the film instability is similar to that found in thermal dewetting, the rim instability is quite different. Two different types of the rim instability have been found. With a polar solvent, the rim instability changes from one type to another with increasing film thickness whereas the unstable rim becomes stable for an apolar solvent.

Journal Article↗

Turing instability mediated by voltage and calcium diffusion in paced cardiac cells.

In cardiac cells, the coupling between the voltage across the cell membrane (V(m)) and the release of calcium (Ca) from intracellular stores is a crucial ingredient of heart function. Under abnormal conditions and/or rapid pacing, both the action potential duration and the peak Ca concentration in the cell can exhibit well known period-doubling oscillations referred to as "alternans," which have been linked to sudden cardiac death. Fast diffusion of V(m) keeps action potential duration alternans spatially synchronized over the approximately 150-mum-length scale of a cell, but slow diffusion of Ca ions allows Ca alternans within a cell to become spatially asynchronous, as observed in some experiments. This finding raises the question: When are Ca alternans spatially in-phase or out-of-phase on subcellular length scales? This question is investigated by using a spatially distributed model of Ca cycling coupled to V(m). Our main finding is the existence of a Turing-type symmetry breaking instability mediated by V(m) and Ca diffusion that causes Ca alternans to become spontaneously out-of-phase at opposite ends of a cardiac cell. Pattern formation is governed by the interplay of short-range activation of Ca alternans, because of a dynamical instability of Ca cycling, and long-range inhibition of Ca alternans by V(m) alternans through Ca-sensitive membrane ionic currents. These results provide a striking example of a Turing instability in a biological context where the morphogens can be clearly identified, as well as a potential link between dynamical instability on subcellular scales and life-threatening cardiac disorders.

Action Potentials↗

Suppression of genome instability by redundant S-phase checkpoint pathways in Saccharomyces cerevisiae.

Cancer cells show increased genome rearrangements, although it is unclear what defects cause these rearrangements. Previous studies have implicated the Saccharomyces cerevisiae replication checkpoint in the suppression of spontaneous genome rearrangements. In the present study, low doses of methyl methane sulfonate that activate the intra-S checkpoint but not the G1 or G2 DNA damage checkpoints were found to cause increased accumulation of genome rearrangements in both wild-type strains and to an even greater extent in strains containing mutations causing defects in the intra-S checkpoint. The rearrangements were primarily translocations or events resulting in deletion of a portion of a chromosome arm along with the addition of a new telomere. Combinations of mutations causing individual defects in the RAD24 or SGS1 branches of the intra-S checkpoint or the replication checkpoint showed synergistic interactions with regard to the spontaneous genome instability rate. PDS1 and the RAD50-MRE11-XRS2 complex were found to be important members of all the S-phase checkpoints in suppressing genome instability, whereas RAD53 only seemed to play a role in the intra-S checkpoints. Combinations of mutations that seem to result in inactivation of the S-phase checkpoints and critical effectors resulted in as much as 12,000-14,000-fold increases in the genome instability rate. These data support the view that spontaneous genome rearrangements result from DNA replication errors and indicate that there is a high degree of redundancy among the checkpoints that act in S phase to suppress such genome instability.

DNA-Binding Proteins↗

Carcinogen-specific induction of genetic instability.

It has been proposed recently that the type of genetic instability in cancer cells reflects the selection pressures exerted by specific carcinogens. We have tested this hypothesis by treating immortal, genetically stable human cells with representative carcinogens. We found that cells resistant to the bulky-adduct-forming agent 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) exhibited a chromosomal instability (CIN), whereas cells resistant to the methylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) exhibited a microsatellite instability (MIN) associated with mismatch repair defects. Conversely, we found that cells purposely made into CIN cells are resistant to PhIP, whereas MIN cells are resistant to MNNG. These data demonstrate that exposure to specific carcinogens can indeed select for tumor cells with distinct forms of genetic instability and vice versa.

Blotting, Western↗

Induction of microsatellite instability by oxidative DNA damage.

Instability of repetitive sequences, both in intronic sequences and within coding regions, has been demonstrated to be a hallmark of genomic instability in human cancer. Understanding how these mutational events arise may provide an opportunity for prevention or early intervention in cancer development. To study the source of this instability, we have identified a region of the beta-lactamase gene that is tolerant to the insertion of fragments of exogenous DNA as large as 1,614 bp with minimal loss of enzyme activity, as determined by antibiotic resistance. Fragments inserted out-of-frame render Escherichia coli sensitive to antibiotic, and compensatory frameshift mutations that restore the reading frame of beta-lactamase can be selected on the basis of antibiotic resistance. We have utilized this site to insert a synthetic microsatellite sequence within the beta-lactamase gene and selected for mutations yielding frameshifts. This assay provides for detection of one frameshift mutation in a background of 10(6) wild-type sequences. Mismatch repair deficiency increased the observed frameshift frequency approximately 300-fold. Exposure of plasmid containing microsatellite sequences to hydrogen peroxide resulted in frameshift mutations that were localized exclusively to the microsatellite sequences, whereas DNA damage by UV or N-methyl-N'-nitro-N-nitrosoguanidine did not result in enhanced mutagenesis. We postulate that in tumor cells, endogenous production of oxygen free radicals may be a major factor in promoting instability of microsatellite sequences. This beta-lactamase assay may provide a sensitive methodology for the detection and quantitation of mutations associated with the development of cancer.

Base Sequence↗

Chromosome instability contributes to loss of heterozygosity in mice lacking p53.

The p53 tumor suppressor protein participates in multiple cellular processes including cell cycle checkpoints and programmed cell death. In cell lines, loss of p53 function is associated with increased genetic instability including aneuploidy, gene amplification, and point mutation. Although similar genetic instability often accompanies the progression of malignancy in tumors, its role in tumor initiation in normal cells is not clear. To study whether or not loss of p53 leads to genetic instability in normal cells in vivo, we have examined mechanisms of loss of heterozygosity (LOH) at the Aprt (adenine phosphoribsyltransferase) and flanking loci in normal fibroblasts and T lymphocytes of p53-deficient mice. Somatic cell variants that arose in vivo as a consequence of genetic or epigenetic alterations abolishing Aprt function were selected and expanded in vitro by virtue of their resistance to 2,6-diaminopurine (DAP). We observed that p53 null mice produced about three times as many DAP-resistant fibroblast colonies than wild-type mice, but the frequency of DAP-resistant T lymphocyte colonies was not significantly changed. Mitotic recombination, but not point mutation, partly accounted for the increase in the frequency of DAP-resistant fibroblasts. Most significantly, chromosome loss/duplication and interstitial deletion, which were extremely rare events in the wild-type mice, represented a significant proportion of LOH events in both fibroblasts and T lymphocytes of p53 null mice. Also, increased interstitial deletion was observed in fibroblasts of p53 heterozygous mice. These data suggest that increased genetic variation, including chromosome instability, starts at the initiation stage of tumorigenesis when functional p53 is absent or reduced.

Aneuploidy↗

Involvement of the nucleotide excision repair protein UvrA in instability of CAG*CTG repeat sequences in Escherichia coli.

Several human genetic diseases have been associated with the genetic instability, specifically expansion, of trinucleotide repeat sequences such as (CTG)(n).(CAG)(n). Molecular models of repeat instability imply replication slippage and the formation of loops and imperfect hairpins in single strands. Subsequently, these loops or hairpins may be recognized and processed by DNA repair systems. To evaluate the potential role of nucleotide excision repair in repeat instability, we measured the rates of repeat deletion in wild type and excision repair-deficient Escherichia coli strains (using a genetic assay for deletions). The rate of triplet repeat deletion decreased in an E. coli strain deficient in the damage recognition protein UvrA. Moreover, loops containing 23 CTG repeats were less efficiently excised from heteroduplex plasmids after their transformation into the uvrA(-) strain. As a result, an increased proportion of plasmids containing the full-length repeat were recovered after the replication of heteroduplex plasmids containing unrepaired loops. In biochemical experiments, UvrA bound to heteroduplex substrates containing repeat loops of 1, 2, or 17 CAG repeats with a K(d) of about 10-20 nm, which is an affinity about 2 orders of magnitude higher than that of UvrA bound to the control substrates containing (CTG)(n).(CAG)(n) in the linear form. These results suggest that UvrA is involved in triplet repeat instability in cells. Specifically, UvrA may bind to loops formed during replication slippage or in slipped strand DNA and initiate DNA repair events that result in repeat deletion. These results imply a more comprehensive role for UvrA, in addition to the recognition of DNA damage, in maintaining the integrity of the genome.

Adenosine Triphosphatases↗

Microsatellite instability in primary brain tumors.

Microsatellite instability has been reported in hereditary colorectal cancer syndrome and in various kinds of human sporadic tumors. It has also been shown in brain tumors, although with conflicting results. In the present study, DNA samples obtained from 20 primary brain tumors (10 glioblastomas, three astrocytomas, five meningiomas, one ependymoma, one hemangiopericytoma) were analyzed to detect microsatellite instability. Nine microsatellites, mono, di-, tri- and tetranucleotide repeat markers, located on nine different chromosomes, were used. Four of the 20 neoplasias (20%) showed microsatellite alterations in tumor DNA with respect to normal DNA. Two glioblastomas and one atypical meningioma (15%) showed additional bands or bands with shift of electrophoretic mobility, whereas allelic loss was observed in two glioblastomas (10%). In one glioblastoma, one allelic loss and one extra allele were observed at two different loci. These data indicate that in primary brain tumors there is not a high genetic instability. Although we used markers with inherently high levels of instability, only sporadic microsatellite alterations were found. Consequently, alterations in the mechanisms of DNA mismatch-repair, the most important cause of replication errors in hereditary and sporadic colorectal cancers, do not seem to play a major role in the oncogenesis of primary brain tumors.

Adult↗

Screening for job loss: development of a work instability scale for traumatic brain injury.

OBJECTIVE: The objective of this study was to explore the concept of work instability (a mis-match between an individual's functional and cognitive abilities and the demands of their job) following traumatic brain injury (TBI) and develop a work instability scale specific to this population. METHOD: Work instability (WI) following TBI was explored through qualitative interviews which were then used to generate items for a work instability scale (WIS). Rasch analysis was used to examine the scaling properties of the TBI-WIS which was then validated against a gold standard of expert vocational assessment by occupational psychologists. RESULTS AND CONCLUSION: The resulting measure is a 36 item, self-administered scale which can be scored in three bands indicating low, medium and high risk of job retention problems. The scale meets modern psychometric requirements for measurement and presents an opportunity in routine clinical practice to take positive action to prevent job loss.

Adolescent↗

Chromosomal instability induced by heavy ion irradiation.

PURPOSE: To establish the dose-response relationship for the induction of chromosomal instability in GM10115 cells exposed to high-energy iron ions (1 GeV/nucleon, mean LET 146 keV/microm) and gold ions (11 GeV/nucleon, mean LET 1450 keV/microm). Past work has established that sparsely ionizing X-rays can induce a long-lived destabilization of chromosomes in a dose-dependent manner at an incidence of approximately 3% per gray. The present investigation assesses the capacity of High-Z and High-energy (HZE) particles to elicit this same endpoint. MATERIALS AND METHODS: Clonal populations derived from single progenitor cells surviving heavy-ion irradiation were analyzed cytogenetically to identify those clones showing a persistent destablization of chromosomes. RESULTS: Dose-response data, with a particular emphasis at low dose (< 1.0 Gy), indicate a frequency of approximately 4% per gray for the induction of chromosomal instability in clones derived from single progenitor cells surviving exposure to iron ions. The induction of chromosomal instability by gold ions was, however, less responsive to applied dose, as the observed incidence of this phenotype varied from 0 to 10% over 1-8 Gy. Both iron and gold ions gave dose-dependent increases in the yield of chromosomal aberrations (both chromosome- and chromatid-type) measured at the first mitosis following irradiation, as well as shoulderless survival curves having D0=0.87 and 1.1 Gy respectively. CONCLUSIONS: Based on the present dose-response data, the relative biological effectiveness of iron ions is 1.3 for the induction of chromosomal instability, and this indicates that heavy ions are only slightly more efficient than X-rays at eliciting this delayed phenotype.

Animals↗