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PubMed2004

Association of pontine small infarction (lacuna) with disturbance of postural stability.

Neuronal degeneration within the brainstem has been reported in patients with impaired postural stability. However, the functional significance of these abnormalities is unknown at present. In the present study, we evaluated the relationship between the presence of pontine lacunae and postural stability measured by stabilometry. A total of 209 consecutive patients without neurological signs were divided into three groups according to the territory of lacunae on magnetic resonance imaging: (1) non-lacunar group, (2) pontine lacunar group, and (3) non-pontine lacunar group. Stabilometry was performed and statokinesigram measures including each Romberg quotient were compared among the three groups. Using multivariate analysis, postural stability was found to be disturbed in the pontine lacunar group compared with the other groups. The data of stabilometry in this group were compatible with disturbance of the central controlling system for keeping postural stability. Pontine lacuna is associated with patients with postural instability. This result may be related to the deterioration of the central coordination system for posture and locomotion.

Adult↗

PubMed1994

Do salt bridges stabilize proteins? A continuum electrostatic analysis.

The electrostatic contribution to the free energy of folding was calculated for 21 salt bridges in 9 protein X-ray crystal structures using a continuum electrostatic approach with the DELPHI computer-program package. The majority (17) were found to be electrostatically destabilizing; the average free energy change, which is analogous to mutation of salt bridging side chains to hydrophobic isosteres, was calculated to be 3.5 kcal/mol. This is fundamentally different from stability measurements using pKa shifts, which effectively measure the strength of a salt bridge relative to 1 or more charged hydrogen bonds. The calculated effect was due to a large, unfavorable desolvation contribution that was not fully compensated by favorable interactions within the salt bridge and between salt-bridge partners and other polar and charged groups in the folded protein. Some of the salt bridges were studied in further detail to determine the effect of the choice of values for atomic radii, internal protein dielectric constant, and ionic strength used in the calculations. Increased ionic strength resulted in little or no change in calculated stability for 3 of 4 salt bridges over a range of 0.1-0.9 M. The results suggest that mutation of salt bridges, particularly those that are buried, to "hydrophobic bridges" (that pack at least as well as wild type) can result in proteins with increased stability. Due to the large penalty for burying uncompensated ionizable groups, salt bridges could help to limit the number of low free energy conformations of a molecule or complex and thus play a role in determining specificity (i.e., the uniqueness of a protein fold or protein-ligand binding geometry).

Crystallography, X-Ray↗

PubMedDate not supplied

[Significance of sagittal stability in knee prosthesis implantation--an analysis of 76 cases with unconstrained joint surface replacement].

ISSUE: How does the sagittal stability influence the outcome in unconstrained knee arthroplasty? METHOD: In order to clarify this aspect, 76 arthroplasties (10 male, 66 female, 39x gonarthrosis, 37x rheumatoid arthritis) in 61 patients with unconstrained primary knee arthroplasty were examined with a mean follow-up of 4 years. The determined values were the HSS-Score, the Knee-Society-Score, the range of motion, the flexion contracture as well as the posterior and anterior drawer with the KT 1000. The laxity was defined as the sum of the anterior and posterior drawer. RESULTS: The mean values measured were 2.9 mm for the anterior drawer, 1.9 mm for the posterior drawer and 4.8 mm for the laxity. The total patient population reached 81.3 points in the Knee Score, 70.9 points in the Function-Score and 80.7 points in the HSS-Score. The medium range of motion was determined as 103.5 degrees, the medium flexion contracture as 3.5 degrees. For an anterior drawer of > 6 mm and a posterior drawer of < 1 mm the results deteriorated significantly. A laxity of 8-11 mm gave the best score results. CONCLUSION: An anterior drawer of < 6 mm, a posterior drawer of 2-5 mm and a laxity of 8-11 mm seem to be recommendable for unconstrained knee arthroplasty.

Aged↗

PubMed2005

[Gait and stability disorders of the elderly. Clinical analysis of a series of 259 patients older than 70 years].

INTRODUCTION: Gait and stability disorders of the elderly are frequent and a cause of disability, but studies on their clinical features and etiology are scarce, including the relationship between both disorders. OBJECTIVES: To evaluate an extensive series of patients with gait and stability disorders, its clinical variants and posible pathogenic significance. PATIENTS AND METHODS: 259 patients older than 70 years consulting for chronic gait and stability symptoms in an outpatients neurologic clinic were retrospectively reviewed. Several clinical and evolution data are analyzed. RESULTS: Mean age was 78.8 years and 61.8% were women. 52 % were hypertensive. 161 cases had disequilibrium, 91 a cautious gait and seven other types of gait abnormality. 11 % had associated dementia. 27 % showed subcortical white matter abnormalities on computed tomography scan. In 28 cases a specific cause could be established. In follow-up 33.5 % worsened. Significant differences between cases of disequilibrium and cautious gait were increased age, functional disability and turn abnormality in the latter. CONCLUSIONS: Disequilibrium and cautious gait of the elderly share some clinical features, have few specific causes and vary from mild cases to a disabling < >.

Accidental Falls↗

PubMed1993

Analysis of a genetic mutation in an electrophoretic variant of the human lactate dehydrogenase-B(H) subunit.

An electrophoretic variant of the lactate dehydrogenase (LDH)-B(H) subunit was discovered in a patient with diabetes mellitus. His LDH activity in serum was slightly lower than normal and the LDH isozyme pattern showed an abnormal migration indicating an LDH-B subunit variant of the fast type. The LDH containing the variant subunit revealed a decreased heat stability. DNA analysis of the variant allele detected a base substitution, an A to G transition, at codon 6 (AAA-->GAA). The mutation resulted in the replacement of a lysine by a glutamic acid (K6E). The change may cause the heat instability and affect the net charge of the variant subunit, resulting in an electrophoretic LDH-B subunit variant of the fast type.

Aged↗

PubMed2005

Jahn-Teller stabilization of a "polar" metal oxide surface: Fe3O4(001).

Using ab initio thermodynamics we compile a phase diagram for the surface of Fe3O4(001) as a function of temperature and oxygen pressures. A hitherto ignored polar termination with octahedral iron and oxygen forming a wavelike structure along the [110] direction is identified as the lowest energy configuration over a broad range of oxygen gas-phase conditions. This novel geometry is confirmed via x-ray diffraction analysis. The stabilization of the Fe3O4(001) surface goes together with dramatic changes in the electronic and magnetic properties, e.g., a half metal to metal transition.

Journal Article↗

PubMed1997

Glucocorticoids increase fatty-acid synthase mRNA stability in fetal rat lung.

Fatty-acid synthase (FAS) is a critical enzyme in surfactant biosynthesis. In fetal lung, glucocorticoids increase synthesis of phosphatidylcholine, the principal lipid component of surfactant, and there is evidence that this effect is mediated by increased expression of the FAS gene. Dexamethasone increases FAS activity, mass, mRNA content, and rate of transcription in cultured explants of fetal rat lung. As previous experiments with actinomycin D suggested that dexamethasone may also increase FAS mRNA content by a posttranscriptional mechanism, we examined the effect of the hormone on FAS mRNA stability. Explants of 19-day fetal rat lungs were cultured for 44 h with and without 100 nM dexamethasone. Some explants were harvested at that point, and others were cultured further with 60 microM 5,6-dichlororibofuranosylbenzimidazole (DRB), an inhibitor of transcription. RNA was then extracted, and FAS mRNA levels were measured by Northern analysis, mRNA stability was assessed by comparing the amount remaining after culture with DRB with the initial level before addition of the inhibitor. The apparent half-life of FAS mRNA was 4 h in control explants cultured without hormone. FAS mRNA stability was increased 84% in the explants cultured with dexamethasone for 44 h and by 40% in those cultured with the hormone for 5 h. We conclude that glucocorticoids enhance expression of the FAS gene in fetal lung by increasing mRNA stability in addition to stimulating transcription.

Actins↗

PubMed2005

Evaluation of the stability of chlortetracycline in granular premixes by monitoring its conversion into degradation products.

A methodology for the evaluation of the stability of chlortetracycline (CTC) in granular premixes is described. This methodology is based on the monitoring of the conversion of CTC into its degradation products by an improved gradient liquid chromatography (LC) method, based on one previously described by our laboratory. Sample preparation involves the extraction of CTC and its degradation products prior to LC analysis, using acidified methanol as extraction solvent. The gradient elution LC method proved to be very sensitive, especially towards the late eluting anhydro derivatives. The use of a Hypersil C8 BDS, 5 microm, 250 mm x 4.6 mm i.d. column is recommended since this column allowed a complete separation of the different impurities from each other and from the main component CTC. The applicability of this approach was demonstrated by the analysis of stability samples.

Anti-Bacterial Agents↗

PubMed2003

High-temporal-resolution analysis demonstrates that ICAM-1 stabilizes WEHI 274.1 monocytic cell rolling on endothelium.

Leukocyte rolling, adhesion, and migration on vascular endothelium involve several sets of adhesion molecules that interact simultaneously. Each of these receptor-ligand pairs may play multiple roles. We examined the role of ICAM-1 in adhesive interactions with mouse aortic endothelial cells (MAECs) in an in vitro flow system. Average rolling velocity of the monocytic cell line WEHI 274.1 was increased on ICAM-1-deficient MAECs compared with wild-type MAECs, both with and without TNF-alpha stimulation. High-temporal-resolution analysis provided insights into the underlying basis for these differences. Without TNF-alpha stimulation, average rolling velocity was slower on wild-type than on ICAM-1-deficient endothelium because of brief (<1 s) pauses. On TNF-alpha-stimulated ICAM-1-deficient endothelium, cells rolled faster because of transient accelerations, producing "jerky" rolling. Firm adhesion to ICAM-1-deficient MAECs was significantly reduced compared with wild-type MAECs, although the number of rolling cells was similar. These results demonstrate directly that ICAM-1 affects rolling velocity by stabilizing leukocyte rolling.

Animals↗

PubMed2003

Modeling the human lumbar spine for assessing spinal loads, stability, and risk of injury.

This article provides a critical review of biomechanical modeling approaches used to estimate spinal loads, stability, and risk of injury. The complete biomechanical analysis of the spine requires a two-stage approach: (1) equilibrium analysis for estimating tissue loads, and (2) stability analysis for estimating structural tolerance of the spine. For each level of analysis, basic principles are reviewed and relevant published models and studies are referenced. Throughout the article, implications for lumbar function and dysfunction derived from the various modeling methods are presented, and their applications are discussed. At the end, future directions for research are identified. Detailed descriptions of selected modeling approaches are provided in the appendices.

Compressive Strength↗

PubMed2005

A model of dynamic sacro-iliac joint instability from malrecruitment of gluteus maximus and biceps femoris muscles resulting in low back pain.

The objective of this work is to propose a biomechanical model of sacro-iliac joint dysfunction as a cause of low back pain. Sacro-iliac joint is known to be a source of low back pain. We also know that it is a very stable joint with little mobility. Surrounding lower limb and back muscles contribute a major part of this stability. Gait analysis studies have revealed an orderly sequence of muscle activation when we walk - that contributes to efficient stabilisation of the joint and effective weight transfer to the lower limb. Gluteus maximus fibres-lying almost perpendicular to the joint surfaces are ideally oriented for this purpose. Biceps femoris is another important muscle that can also influence joint stability by its proximal attachment to sacrotuberous ligament. Altered pattern of muscle recruitment has been observed in patients with low back pain. But we do not know the exact cause-effect relationship. Because of its position as a key linkage in transmission of weight from the upper limbs to the lower, poor joint stability could have major consequences on weight bearing. It is proposed that sacro-iliac joint dysfunction can result from malrecruitment of gluteus maximus motor units during weight bearing. This results in compensatory biceps over activation. The resulting soft tissue strain and joint instability may manifest itself in low back pain. If our hypothesis holds true, it may have positive implications for patients with sacro-iliac joint dysfunction - who could be offered a definite diagnosis and targeted physiotherapy. It may be possible to identify patients early in a primary care setting and offer direct physio referral. They could benefit from exercises to improve strengthening and recruitment of the affected muscles.

Buttocks↗

PubMed2026

Genomic characterization and therapeutic potential of five broad-spectrum lytic bacteriophages against multidrug-resistant avian pathogenic Escherichia coli (APEC).

UNLABELLED: Colibacillosis, caused by avian pathogenic Escherichia coli (APEC), results in substantial economic losses in global poultry production. The emergence of multidrug-resistant (MDR) APEC poses zoonotic risks through horizontal transfer of antimicrobial resistance (AMR) genes. Bacteriophage therapy emerges as a safe alternative to antibiotherapy; however, comprehensive characterization of phages targeting MDR-APEC from diverse geographical regions remains limited. We isolated five lytic bacteriophages from poultry fecal samples collected from five Indian states and characterized them through morphological analysis, physiological stability testing, whole-genome sequencing, and in vivo efficacy assessment. Host range was determined against APEC isolates, and therapeutic potential was validated in the Galleria mellonella infection model. All phages showed Myovirus-like morphology and stability across physiologically relevant temperatures (up to 55°C-70°C) and pH conditions (3-11). Phages were classified as Escherichia phage vB_EcoM_fRPOT1, vB_EcoM_fDMYT1, vB_EcoM_fBSZT1, vB_EcoM_fUAMT1, and vB_EcoM_fPKPT2. Their genome size ranges from 170 to 356 kb, belonging to three distinct genera: Dhakavirus, Gaprivervirus, and Asteriusvirus. Genomic analysis confirmed the absence of antimicrobial resistance, virulence, toxin, or lysogeny genes. Fifty-one APEC strains were isolated, of which 23 (45.1%) were MDR. Individual phages lysed 37%-51% of tested APEC and 17%-39% of MDR strains. Three phages (fBSZT1, fUAMT1, and fPKPT2) significantly improved larval survival to 60%-80% at an MOI of 10 in G. mellonella infection models compared to the untreated control. This study establishes a well-characterized phage bank targeting MDR-APEC strains, providing a foundation for developing phage-based interventions to reduce antibiotic dependency and mitigate AMR transmission risks under the One Health framework. IMPORTANCE: The overuse of antibiotics in poultry farming has created a crisis. The multidrug-resistant (MDR) bacteria threaten both animal health and human safety through the food chain. When antibiotics fail, farmers face devastating losses, and resistant bacteria can transfer to humans through consumption or environmental contamination. Bacteriophages offer a practical solution as they kill target bacteria without harming beneficial microbes or leaving chemical residues. Our comprehensive characterization confirms that these five phages are safe and effective as they lack any resistance or toxin genes and rescue 60%-80% of infected larvae. This represents a characterized phage bank targeting the specific resistant strains in Indian poultry. By providing a validated alternative to antibiotics, this work supports sustainable food production while reducing the spread of antimicrobial resistance from farms to humans.

Animals↗

PubMed2002

Cefotaxime, des-Cefotaxime and Ceftazidime: in vitro activity and stability to hydrolysis from TEM-derived extended spectrum beta-lactamases.

Beta-lactams represent one of the most important class of antibiotics for the treatment of infectious diseases due to pathogenic bacteria. The selective pressure exerted from the wide spread use of third generation cephalosporins generated mutant beta-lactamases belonging mainly to the TEM or SHV family that are able to extend the activity spectrum of hydrolysis. Moreover, extended spectrum cephalosporins are often a good choice in clinical practice towards Enterobacteriaceae. Here we report a comparative analysis of stability between cefotaxime, desacetyl-cefotaxime and ceftazidime with some common TEM-derivatives extended spectrum beta-lactamases.

Cefotaxime↗

PubMedDate not supplied

[Amperometric biosensor for lactate analysis in wines and grape must during fermentation].

The amperometric biosensor based on lactate oxidase for determination of lactate has been developed, and two methods of immobilization of lactate oxidase on the surface of industrial screen-printed platinum electrodes SensLab were compared. A sensor with immobilized in the Resydrol polymer lactate oxidase by the method of physical adsorption is characterized of narrow dynamic range and greater response value in comparison with a biosensor based on immobilised in poly(3,4-ethylenedioxythiophene) lactate oxidase by the method of electrochemical polymerization. Operational stability of the biosensor developed was studied and it was shown, that the immobilization method does not influence their stability. The analysis of the lactate in wine and during wine fermentation has been conducted. High correlation of the data obtained by means of amperometric lactate biosensor and a standard method of an ionic chromatography has been shown. The developed biosensor could be applied in the food industry for the control and optimization of the wine fermentation process, and quality control of wine.

Biosensing Techniques↗

PubMed2006

High-resolution structure of the p53 core domain: implications for binding small-molecule stabilizing compounds.

The p53 transcriptional regulator is the most frequently mutated protein in human cancers and the majority of tumor-derived p53 mutations map to the central DNA-binding core domain, with a subset of these mutations resulting in reduced p53 stability. Here, the 1.55 A crystal structure of the mouse p53 core domain with a molecule of tris(hydroxymethyl)aminomethane (Tris) bound through multiple hydrogen bonds to a region of p53 shown to be important for repair of a subset of tumor-derived p53-stability mutations is reported. Consistent with the hypothesis that Tris binding stabilizes the p53 core domain, equilibrium denaturation experiments are presented that demonstrate that Tris binding increases the thermodynamic stability of the mouse p53 core domain by 3.1 kJ mol(-1) and molecular-dynamic simulations are presented revealing an overall reduction in root-mean-square deviations of the core domain of 0.7 A when Tris is bound. It is also shown that these crystals of the p53 core domain are suitable for the multiple-solvent crystal structure approach to identify other potential binding sites for possible core-domain stabilization compounds. Analysis of the residue-specific temperature factors of the high-resolution core-domain structure, coupled with a comparison with other core-domain structures, also reveals that the L1, H1-S5 and S7-S8 core-domain loops, also shown to mediate various p53 activities, harbor inherent flexibility, suggesting that these regions might be targets for other p53-stabilizing compounds. Together, these studies provide a molecular scaffold for the structure-based design of p53-stabilization compounds for development as possible therapeutic agents.

2-Propanol↗

PubMed1995

The effect of passenger load on unstable vehicles in fatal, untripped rollover crashes.

Consumers may be unaware of the risk of rollover crashes posed by passenger loads in vehicles with poor roll stability. This analysis demonstrates that certain sports utility vehicles and small pickup trucks have designs that are so unstable that the weight of the passengers in the vehicle affects its propensity to roll over. This effect occurs even though the weight of the loaded vehicle is less than the manufacturer's gross vehicle weight rating. The risk of a fatal, "untripped" rollover crash in vehicles with low roll stability is increased as each passenger is added to the vehicle load.

Accidents, Traffic↗

PubMed2000

Amino- and carboxy-terminal PEST domains mediate gastrin stabilization of rat L-histidine decarboxylase isoforms.

Control of enzymatic function by peptide hormones can occur at a number of different levels and can involve diverse pathways that regulate cleavage, intracellular trafficking, and protein degradation. Gastrin is a peptide hormone that binds to the cholecystokinin B-gastrin receptor and regulates the activity of L-histidine decarboxylase (HDC), the enzyme that produces histamine. Here we show that gastrin can increase the steady-state levels of at least six HDC isoforms without affecting HDC mRNA levels. Pulse-chase experiments indicated that HDC isoforms are rapidly degraded and that gastrin-dependent increases are due to enhanced isoform stability. Deletion analysis identified two PEST domains (PEST1 and PEST2) and an intracellular targeting domain (ER2) which regulate HDC protein expression levels. Experiments with PEST domain fusion proteins demonstrated that PEST1 and PEST2 are strong and portable degradation-promoting elements which are positively regulated by both gastrin stimulation and proteasome inhibition. A chimeric protein containing the PEST domain of ornithine decarboxylase was similarly affected, indicating that gastrin can regulate the stability of other PEST domain-containing proteins and does so independently of antizyme/antizyme inhibitor regulation. At the same time, endoplasmic reticulum localization of a fluorescent chimera containing the ER2 domain of HDC was unaltered by gastrin stimulation. We conclude that gastrin stabilization of HDC isoforms is dependent upon two transferable and sequentially unrelated PEST domains that regulate degradation. These experiments revealed a novel regulatory mechanism by which a peptide hormone such as gastrin can disrupt the degradation function of multiple PEST-domain-containing proteins.

5' Untranslated Regions↗

PubMed2003

Analysis of altered G-protein subunit accumulation in Cryphonectria parasitica reveals a third Galpha homologue.

Heterotrimeric G-proteins mediate many responses of eukaryotic cells to external stimuli and have been shown to be important for fungal pathogenicity. In this study, we explored the accumulation of G-protein subunits of the chestnut blight fungus, Cryphonectria parasitica, in mutant strains deleted for one or more putative partner subunits. Using a series of extraction buffers and immunoblot end-point dilution analysis, we established a convenient method to assess the relative abundance of these membrane-associated proteins. Disruption of either cpg-1, which encodes the Galpha subunit CPG-1, or cpgb-1, the Gbeta subunit CPGB-1, consistently reduced the level of its presumptive partner protein. This was not observed in the case of a second Galpha subunit, CPG-2, suggesting that CPG-1 and CPGB-1 regulate each other's stability. Further, analysis of transcript levels indicated that the Galpha and Gbeta protein turnover rates were increased in the mutant strains. Additionally, a previously unidentified protein that was cross-reactive with anti-CPG-1 antiserum was found to be enhanced in liquid culture. We describe the sequence of a new Galpha subunit, CPG-3, that is most similar to three other filamentous fungal Galpha proteins that form a phylogenetically distinct grouping.

Amino Acid Sequence↗