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 613 records · Page 34Linked to original sources
PubMed2003

Induced genomic instability in irradiated germ cells and in the offspring; reconciling discrepancies among the human and animal studies.

Many studies confirmed that radiation induces genomic instability in whole-body systems. However, the results of the studies are not always consistent with each other. Attempts are made in the present review to resolve the discrepancies. Many of the studies in human and experimental animals utilize the length change mutation of minisatellite sequences as a marker of genomic instability. Minisatellite sequences frequently change their length, and the data obtained by conventional Southern blotting give rather qualitative information, which is sometimes difficult to scrutinize quantitatively. This is the problem inevitably associated with the study of minisatellite mutations and the source of some conflicts among studies in humans and mice. Radiation induction of genomic instability has also been assessed in whole-body experimental systems, using other markers such as the mouse pink-eyed unstable allele and the specific pigmentation loci of medaka fish (Oryzias latipes). Even though there are some contradictions, all these studies have demonstrated that genomic instability is induced in the germ cells of irradiated parents, especially of males, and in offspring born to them. Among these, transmission of genomic instability to the second generation of irradiated parents is limited to the mouse minisatellite system, and awaits further clarification in other experimental systems.

Animals↗
PubMed2006

Effects of hTERT on metal ion-induced genomic instability.

There is currently a great interest in delayed chromosomal and other damaging effects of low-dose exposure to a variety of pollutants which appear collectively to act through induction of stress-response pathways related to oxidative stress and ageing. These have been studied mostly in the radiation field but evidence is accumulating that the mechanisms can also be triggered by chemicals, especially heavy metals. Humans are exposed to metals, including chromium (Cr) (VI) and vanadium (V) (V), from the environment, industry and surgical implants. Thus, the impact of low-dose stress responses may be larger than expected from individual toxicity projections. In this study, a short (24 h) exposure of human fibroblasts to low doses of Cr (VI) and V (V) caused both acute chromosome damage and genomic instability in the progeny of exposed cells for at least 30 days after exposure. Acutely, Cr (VI) caused chromatid breaks without aneuploidy while V (V) caused aneuploidy without chromatid breaks. The longer-term genomic instability was similar but depended on hTERT positivity. In telomerase-negative hTERT- cells, Cr (VI) and V (V) caused a long lasting and transmissible induction of dicentric chromosomes, nucleoplasmic bridges, micronuclei and aneuploidy. There was also a long term and transmissible reduction of clonogenic survival, with an increased beta-galactosidase staining and apoptosis. This instability was not present in telomerase-positive hTERT+ cells. In contrast, in hTERT+ cells the metals caused a persistent induction of tetraploidy, which was not noted in hTERT- cells. The growth and survival of both metal-exposed hTERT+ and hTERT- cells differed if they were cultured at subconfluent levels or plated out as colonies. Genomic instability is considered to be a driving force towards cancer. This study suggests that the type of genomic instability in human cells may depend critically on whether they are telomerase-positive or -negative and that their sensitivities to metals could depend on whether they are clustered or diffuse.

Apoptosis↗
PubMed2003

End-to-end fusion of linear deleted chromosomes initiates a cycle of genome instability in Streptomyces ambofaciens.

Two mutant strains harbouring a linear chromosome whose size reached 13 Mb (versus approximately 8 Mb for the wild type) were characterized. This chromosomal structure resulted from the fusion in inverted orientation of two chromosomes partially deleted on the same arm. The fusion occurred by illegitimate recombination between 6 bp repeats. This chromosomal structure was inherited in strict association with a high level of genetic instability (30% of mutants in a single progeny, phenomenon also called hypervariability) and chromosomal instability. In contrast, derivatives, which did not retain the chromosome fusion, showed a wild-type-like instability frequency (c. 1%). Stabilization of the chromosomal structure occurred by chromosome arm replacement or circularization. A high variability of the terminal inverted repeat (TIR) length in the rescued chromosomes (from 5 kb to approximately 1.4 Mb for linear derivatives) was observed. Mutant lineages harbouring the chromosomal fusion are characterized by a highly heterogeneous distribution of DNA in the spores, by the presence of spores without DNA as well as aberrant sporulation figures, and by the production of spores with a low germination rate. The wild-type characteristics were restored in the descendants, which lost the chromosomal fusion. Thus, the fusion of deleted chromosomes initiates a cycle of chromosome instability sharing several levels of analogy with the behaviour of dicentric chromosomes in eukaryotes. We propose that the high instability of the fused chromosomes results from the duplication of a region involved in partitioning of the chromosomes (parAB-oriC ).

Chromosomes, Bacterial↗
PubMed2002

Arthroscopic stabilization of anterior shoulder instability: a review of the literature.

The treatment of anterior glenohumeral instability has been a topic of debate in the recent literature. Current surgical management of shoulder instability has included a variety of open and arthroscopic procedures. Open techniques for anterior reconstruction have been quite successful in preventing recurrent dislocations and continue to be the gold standard of care. In an attempt to address some of the disadvantages associated with open procedures, arthroscopic stabilization procedures have been developed. Arthroscopic capsuloligamentous repair presumably has clear advantages including better cosmesis, decreased perioperative morbidity, and a possible decrease in the loss of external rotation. Advances in arthroscopic instrumentation and improved arthroscopic techniques have increased the popularity of arthroscopic stabilization. The art of diagnosing the anatomic pathology associated with instability and proper patient selection continues to evolve. Most previous reports of arthroscopic stabilization have included small numbers of patients, variable patient pathology, and a variety of surgical techniques, making comparisons between stabilization procedures difficult. Arthroscopy can be valuable in both the confirmation of the degree and severity of the instability and to correct the pathoanatomy responsible for the instability.

Adult↗
PubMedDate not supplied

[Postoperatively recurring instability of the shoulder--a fault analysis in 46 cases].

AIM: The successful operative stabilization of the shoulder joint is a demanding surgical procedure. The causality of shoulder instability is complex with in some cases multiple lesions in different anatomical structures. The surgeon has to understand the complexity of factors causing instability in order to be therapeutically successful. The aim of the study was to document the intraoperative pathology in revision instability surgery. METHOD: 46 patients with recurrent postoperative instability were included (8 female, 38 male, follow-up > 12 months). After diagnostic arthroscopy an open revision surgery was performed in all cases. RESULTS: In 19 cases (40%) an insufficient surgical procedure was performed (inadequate capsular shift with worn out labral tissue). Selection of an incorrect surgical technique was the reason for revision in 12 patients (25%). Anamnestically 5 patients reported a re-injury, whereas objectively only one patient described an adequate trauma. The most frequent finding was an open rotator interval (persisting Foramen Weitbrecht), which was seen in 22 cases (46%). CONCLUSION: A stable range of motion of the shoulder is achieved by a variety of different factors, which leads in most instances to a combination of pathological changes in case of a dislocated shoulder. To understand the contributing factors of an instable shoulder joint is a necessity to carry out a successful surgical procedure.

Adult↗
PubMed2005

Imaging of spine instability.

Spine instability is an important cause of back pain and disability. The most common causes of clinical instability are spinal trauma, congenital anomalies, inflammatory disorders, degenerative disease, and prior surgery. Imaging of spine instability relies on both static anatomic imaging and functional assessment of spine motion. This chapter reviews the complexity of defining instability and reviews the common antecedents of spine instability and their imaging features.

Humans↗
PubMed2005

Elbow instability: the orthopedic approach.

In recent years significant progress has been made in the diagnosis and treatment of elbow instability. Elbow instability represents a spectrum from the acute traumatic dislocation to chronic laxity resulting in transient joint subluxation. In general, acute elbow dislocations represent the second most common joint dislocation in the adult population and the most common joint dislocation in the pediatric age group. This manuscript reviews the anatomy of the elbow joint as it relates to elbow instability. It then discusses the mechanism and classification of elbow instability and outlines treatment options available for acute and chronic elbow instability.

Elbow Joint↗
PubMed2006

[Magnetic resonance imaging of glenohumeral instability].

Conventional MR imaging and MR arthrography are established diagnostic imaging modalities for investigating shoulder instability. Since there are currently various surgical shoulder stabilization methods as well as conservative treatment strategies, the role of imaging is to provide diagnostic information to help determine the therapeutic approach. Whereas conventional MR imaging is usually sufficient for the evaluation of acute shoulder injuries due to the presence of a posttraumatic joint effusion, MR arthrography is the imaging modality of choice for chronic shoulder instability. Atraumatic and microtraumatic instability of the shoulder must be distinguished from traumatic instability since clinical findings and secondary or associated injuries differ from those of traumatic instability. Injuries of the IGHL-complex can be reliably diagnosed with MR arthrography. Traumatic anteroinferior luxation causes labroligamentous injuries at the glenoid insertion (Bankart-, Perthes-, ALPSA-, and non-classifiable chronic lesions) and injuries of the IGHL and its humeral insertion (HAGL-, BHAGL-, and floating AIGL-lesions). The type of injury and extent of degenerative changes or scarring that can be assessed with MR arthrography influence the therapeutic approach and in particular the decision between arthroscopic and open surgical methods of stabilization.

Arthrography↗
PubMedDate not supplied

[The value of ultrasound in evaluating instabilities of the glenohumeral joint].

In a prospective study we evaluated diagnostic ultrasound investigation for shoulder instabilities. We measured the passive aptranslation In 150 healthy persons in relation to the dorsal glenoid as well as the inferior subluxation in relation to the acromion. After establishing normative datas we measured 23 patient with unidirectional instabilities and 34 with multidirectional instabilities. The humeral head position of a normal joint is 8 to 10 mm dorsally to the glenoid. In the control group the anterior translation of the dominant shoulder is significantly higher as in the nondominant shoulder (student-t-test; p less than 0.0045). Patients with anterior instabilities showed a significant increase of anterior translation in the injured shoulder (student-t-test; p less than 0.0001). In comparison with the control group there is a significant increase of downward subluxation in patients with multidirectional instabilities (chi 2 alpha less than 0.05). In habitual or voluntary dislocations the relation of the humeral head to the glenoid can be judged statically and dynamically. Secondary signs of dislocation (Hill-Sachs lesions, joint effusion) are evident.

Adolescent↗
PubMed1998

MR abnormalities of the intervertebral disks and adjacent bone marrow as predictors of segmental instability of the lumbar spine.

PURPOSE: To assess whether MR abnormalities of the intervertebral disks and adjacent bone marrow can predict segmental instability of the lumbar spine as diagnosed on functional radiographs. MATERIAL AND METHODS: A consecutive review was made of 60 patients examined with MR imaging and with lateral flexion and extension views of the lumbar spine. Sagittal T1- and T2-weighted images were evaluated blindly with regard to abnormalities of the intervertebral disk and the adjacent bone marrow. Segmental instability was diagnosed when a.p. translation of 3 mm or more was present on the functional radiographs. Moreover, the presence of osteophytes was evaluated on lateral standard radiographs. RESULTS: Of a total of 300 segments, 32 (10.7%) were unstable. Anular tears were the most relevant MR finding. Their sensitivity, specificity, and positive and negative predictive values for segmental instability were 18.8%, 97.0%, 42.9% and 90.9%. The corresponding values for traction osteophytes were 12.5%, 98.1%, 44.4% and 90.4%. Abnormalities of bone marrow were not significantly related to segmental instability (p=0.35). CONCLUSION: Functional radiographs should be considered in patients with anular tears or traction osteophytes. No correlation was found between segmental instability and abnormalities of bone marrow adjacent to the endplates.

Adult↗
PubMed2006

Amount of ulnar resection is a predictive factor for ulnar instability problems after the Sauvé-Kapandji procedure: a retrospective study of 44 patients followed for 1-13 years.

BACKGROUND: The Sauvé-Kapandji procedure can result in instability of the proximal ulnar stump. PATIENTS AND METHODS: We reviewed 44 patients (mean follow-up time 6 (0.6-13) years) to investigate predictive factors for ulnar instability after Sauvé-Kapandji operation. We used several scores including an instability score specifically designed for this study. RESULTS: Patients with a longer proximal ulnar stump had significantly lower instability scores, significantly better Mayo Modified wrist scores and DASH scores, and also less pain than those with shorter proximal ulna. INTERPRETATION: If the shortening of the proximal stump is less than 35 mm, a reliable improvement in motion and a high patient satisfaction can be expected. The risk of a painful ulnar instability is related to the amount of resection, and can be reduced by creating a long upper ulnar stump.

Adolescent↗
PubMed2004

Chromosomal instability at common fragile sites in Seckel syndrome.

Seckel syndrome (SCKL) is a rare, genetically heterogeneous disorder, with dysmorphic facial appearance, growth retardation, microcephaly, mental retardation, variable chromosomal instability, and hematological disorders. To date, three loci have been linked to this syndrome, and recently, the gene encoding ataxia-telangiectasia and Rad3-related protein (ATR) was identified as the gene mutated at the SCKL1 locus. The ATR mutation affects splicing efficiency, resulting in low levels of ATR in affected individuals. Elsewhere, we reported increased instability at common chromosomal fragile sites in cells lacking the replication checkpoint gene ATR. Here, we tested whether cells from patients carrying the SCKL1 mutation would show increased chromosome breakage following replication stress. We found that, compared with controls, there is greater chromosomal instability, particularly at fragile sites, in SCKL1-affected patient cells after treatment with aphidicolin, an inhibitor of DNA polymerase alpha and other polymerases. The difference in chromosomal instability between control and patient cells increases at higher levels of aphidicolin treatment, suggesting that the low level of ATR present in these patients is not sufficient to respond appropriately to replication stress. This is the first human genetic syndrome associated with increased chromosome instability at fragile sites following replication stress, and these findings may be related to the phenotypic findings in patients with SCKL1.

Abnormalities, Multiple↗
PubMed2004

Destructive cycles: the role of genomic instability and adaptation in carcinogenesis.

Classical theories of carcinogenesis postulate that the accumulation of several somatic mutations is responsible for oncogenesis. However, these models do not explain how non-mutagenic carcinogens cause cancer. In addition, known mutation rates appear to be insufficient to account for observed cancer rates. Moreover, the current theory doesn't easily account for the long latencies observed in human cancers. Proponents of an aneuploidy-driven theory of carcinogenesis suggest that genomic instability has a causative role in carcinogenesis. In support of this theory, pre-neoplastic cells frequently display genomic instability while normal cells do not. Data obtained from a variety of model organisms have revealed that disruption of the cell cycle controls required for homeostasis results in the acquisition of genomic instability. Subsequently, this genomic instability becomes self-propagating via 'destructive cycles' and provides a medium for cellular selection and adaptation. Genomic instability allows numerous genetic and epigenetic alterations to accumulate during carcinogenesis without markedly changing phenotype until they are qualitatively or quantitatively sufficient to be selectively advantageous in the tumor microenvironment. Observations of adaptation in tumor cell populations and application of chaos theory may help elucidate the mechanism that drives the enormous genetic heterogeneity observed in tumors and provide insights into the development of new therapeutic cancer interventions and treatments.

Animals↗
PubMed2004

Baseline levels of chromosome instability in the human lymphoblastoid cell TK6.

Induced genomic instability in the human B lymphoblastoid cell line TK6 manifests itself as increases in end-to-end chromosome fusions and non-reciprocal chromosome translocations. It is not associated with elevated frequencies of specific locus mutations or other cytogenetic alterations. Previous studies on a limited number of cells and end-points suggested that induced instability in TK6 mirrors spontaneous instability in terms of the types of alterations observed. In the present study we expanded on our previous analysis to include more cells and more end-points in order to derive a more precise measure of spontaneous instability in TK6 cells. The frequency of normal growth rate thymidine kinase mutants (TK(-/-)), measured in 44 independently isolated clones, was 2.73 +/- 0.78 x 10(-6)/cell, while that for slow growth mutants was 2.39 +/- 0.52 x 10(-6)/cell. These are similar to the frequencies observed for HPRT mutants in primary human cells. There was wide variation in chromatid break frequencies, but the average break frequency, at 0.04+/-0.01 breaks/cell, was only slightly higher than that reported for primary human cells. In contrast, the dicentric frequency of 0.006/cell was more than 10-fold higher for TK6 cells than that reported for normal primary human cells. Furthermore, the dicentrics in TK6 cells are unusual in that they are the result of end-to-end chromosome fusions. TK6 cells also show much higher levels of non-reciprocal chromosome translocations than are usually observed in primary human cells. The results suggest an inherent instability in TK6 cells that differs from what is observed in primary cells in that it affects the frequency of end-to-end chromosome fusions and non-reciprocal chromosome translocations, but not TK gene mutations or other cytogenetic alterations.

B-Lymphocytes↗
PubMed2006

Replication in mammalian cells recapitulates the locus-specific differences in somatic instability of genomic GAA triplet-repeats.

Friedreich ataxia is caused by an expanded (GAA.TTC)n sequence in intron 1 of the FXN gene. Small pool PCR analysis showed that pure (GAA.TTC)44+ sequences at the FXN locus are unstable in somatic cells in vivo, displaying both expansions and contractions. On searching the entire human and mouse genomes we identified three other genomic loci with pure (GAA.TTC)44+ sequences. Alleles at these loci showed mutation loads of <1% compared with 6.3-30% for FXN alleles of similar length, indicating that somatic instability in vivo is regulated by locus-specific factors. Since distance between the origin of replication and the (CTG.CAG)n sequence modulates repeat instability in mammalian cells, we tested if this could also recapitulate the locus-specific differences for genomic (GAA.TTC)n sequences. Repeat instability was evaluated following replication of a (GAA.TTC)115 sequence in transfected COS1 cells under the control of the SV40 origin of replication located at one of five different distances from the repeat. Indeed, depending on the location of the SV40 origin relative to the (GAA.TTC)n sequence, we noted either no instability, predominant expansion or both expansion and contraction. These data suggest that mammalian DNA replication is a possible mechanism underlying locus-specific differences in instability of GAA triplet-repeat sequences.

Adult↗
PubMedDate not supplied

Subacute instability of the cervical spine.

The purpose of this article is to describe a new entity, subacute instability of the cervical spine. It is defined as the development of radiographic evidence of cervical instability within 3 weeks of a cervical spine injury when initial adequate roentgenograms show no bony or soft tissue abnormality. Six patients who conform to this definition are reported. Each was found to have developed neurologic deficit and radiographic evidence of instability of the cervical spine on repeat examination when none was present initially. There were four unilateral facet dislocations (two C5-C6, one C6-C7, one C4-C5), one perched facet (C5-C6), and one extension subluxation (C4-C5). The mechanism of subacute instability is thought to be due to the elastic and plastic deformation of the ligamentous structures and discs of the cervical spine. An algorithm has been developed and is described for evaluation of patients with cervical trauma and initial normal radiographs. By alerting physicians to the entity of subacute instability of the cervical spine, it is hoped that injuries of this nature will be discovered so that appropriate treatment can be rendered before a fixed deformity develops.

Adult↗
PubMed1996

Factors related to the severity of myelopathy in atlantoaxial instability.

STUDY DESIGN: This study retrospectively reviewed the factors seemingly associated with neurologic symptoms in 46 patients with atlantoaxial instability. OBJECTIVES: This study revealed the most significant factors related to the severity of myelopathy and surgical prognosis of atlantoaxial instability. SUMMARY OF BACKGROUND DATA: Spinal morphometry has been reported to provide a useful means of predicting the prognosis of cervical spondylotic myelopathy after surgery. However, no quantitative and statistical evaluation of this method has been reported in atlantoaxial instability. Furthermore, there is a poor correlation between neurologic deficit and plain radiographic findings of atlantoaxial instability. METHODS: Four times of clinical information were investigated, six parameters were measured on radiographs, and two morphometric parameters of the spinal cord were measured. These parameters were used as predictor variables. Three multiple regression analyses were carried out, using pre- and post-treatment Japanese Orthopaedic Association scores as criteria variables. RESULTS: Pretreatment Japanese Orthopaedic Association scores were found to correlate with the spinal compression ratio, history of trauma, and the C1-C2 ratio. Postoperative Japanese Orthopaedic Association scores correlated with preoperative Japanese Orthopaedic Association scores, the C1-C2 ratio, and the compression ratio. The multiple coefficient of determination was 93.2%. The recovery rate correlated with the C1-C2 ratio and age. CONCLUSIONS: Neurologic symptoms were found to be closely related to the morphology of the spinal cord. Compression ratio and the C1-C2 ratio were found to be useful in understanding neurologic symptoms. The C1-C2 ratio seems to serve as an important predictor of the prognosis of atlantoaxial instability.

Adolescent↗
PubMed1998

Disc degeneration and cervical instability. Correlation of magnetic resonance imaging with radiography.

STUDY DESIGN: An imaging study was designed to evaluate disc degeneration and segmental instability in the cervical spine. OBJECTIVES: To compare the magnetic resonance imaging assessment of disc degeneration with the conventional plain radiographic evaluation of cervical segmental instability. SUMMARY OF BACKGROUND DATA: No studies have been conducted to investigate the association of disc degeneration with cervical instability. METHODS: Two hundred sixty consecutive patients with suspected cervical spine disorders were analyzed for horizontal and angular displacements on lateral flexion and extension radiographs and disc degeneration on T2-weighted magnetic resonance images of the cervical vertebrae. RESULTS: In all intervertebral levels, the grade of disc degeneration increased significantly (P < 0.01) with age. Cervical instability was identified in 151 segments (14.5%) and correlated with Grade 1 and Grade 2 degeneration in the intervertebral discs (P < 0.01). CONCLUSIONS: Cervical segmental instability may indicate early degeneration of intervertebral disc in the cervical vertebrae.

Adult↗