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PubMed1996

Challenging behaviour: the effectiveness of specialist support teams.

Two specialist community services for people with learning disabilities and challenging behaviour were evaluated over approximately 3 years. Intervention effectiveness was assessed with respect to changes in subjects' skills, challenging behaviours, mental health and quality of life, and to changes in staff morale. Subjects assessed as having challenging behaviour but not referred for specialist input were also studied. Comparison of changes in referred and non-referred samples over time showed minor differences only, indicating little intervention effect and demonstrating stability in the comparison sample. Analysis of the two services separately yielded different results. Positive client change was evident with respect to one service, whilst little change was noted with respect to the other. There was little evidence to suggest that either service had any effect on staff morale. Differences between the two services in terms of structure, staffing characteristics and operational policies are discussed as possible factors in the differential results obtained. A major issue raised by the study concerns the quality of settings from which the subjects were referred for specialist support. This is discussed as a factor which may limit the effectiveness of specialist input.

Adolescent↗
PubMed1997

Anterior instrumentation in the management of thoracolumbar burst fractures.

Anterior instrumentation in the treatment of thoracolumbar fractures has progressed significantly during the past 2 decades. These fixation systems have evolved to meet the anatomic, biomechanical, and imaging challenges associated with internal fixation of the thoracolumbar spine. The evolution of these devices will be reviewed, and from this, the indications and surgical techniques necessary for the safe and effective use of the device will be discussed. This study also reports the authors' initial clinical experience using the Z plate anterior thoracolumbar plating system in the treatment of thoracolumbar burst fractures. The study consists of 12 consecutive adult patients who underwent a 1-stage anterolateral decompressive and stabilization procedure for burst fractures from T9-L3. The indications for surgery included neurologic deficits, deformity, progressive kyphosis, and late pain. Ten of the 12 patients maintained their postoperative sagittal alignment or a significant portion of their kyphosis reduction. Two patients with severe kyphotic deformities greater than 50 degrees lost 10 degrees and 20 degrees of their reduction at last followup. All 3 patients with neurologic deficits recovered. There were no neurologic or perioperative complications. Eleven of the 12 patients obtained a good or excellent functional outcome. Anterior arthrodesis using instrumentation stabilization after a 1-stage anterolateral decompression and reduction procedure can yield successful clinical results in the treatment of thoracolumbar burst fractures.

Adolescent↗
PubMed1988

Marker chromosome stability associated with neoplastic transformation of human uroepithelial cells.

Chromosome studies were performed on three independently derived tumor cell lines established from carcinomas induced in nude mice after innoculation of SV40 immortalized human uroepithelial cells that had been treated with methylcholanthrene. Tumor 1 was an undifferentiated carcinoma, while tumors 7 and 9 were both squamous carcinomas. After six to eight passages in vitro the tumor cells were each reinoculated into other nude mice to yield secondary tumors (1.1 and 7.1). Chromosome studies on both primary and secondary tumors demonstrated the same distinctive chromosome markers. Tumors 1 and 1.1 shared the same histopathology in addition to the same modal chromosome number and identical chromosomal duplications and deficiencies; the same was true of tumors 7 and 7.1. Tumor 9, which did not yield a secondary tumor, nevertheless showed the same chromosome pattern in different passages. The stability of the characteristic marker chromosomes in the three tumor cell lines distinguishes these malignant lines from the nonmalignant SV40 transformed parent line from which the three tumors derived because the parent line was characterized by extreme marker instability. This suggests that the stable marker chromosomes that characterize the tumor cell lines may be critical for their tumorigenicity, and that evolution of an adaptive neoplastic genome may select for cytogenetic stability as long as there are no new selective pressures.

Animals↗
PubMed1992

Consistency and change in patterns of social drinking: a 6-year follow-up of the Finnish Twin Cohort.

In 1975 and again in 1981, all adult twins in the population-based Finnish Twin Cohort were administered postal questionnaires yielding data on self-reported frequency and quantity of alcohol use. The longitudinal results provide information on the age-to-age stability of social drinking patterns among 13,404 (twin) individuals aged 18 to 43 at baseline; model-fitting the cross-temporal consistency of the twins' reported alcohol use yields unique estimates of the contribution of genetic and environmental factors to their individual age-to-age stabilities. Mean consumption levels did not change between 1975 and 1981. Patterns of social drinking were more stable in older (aged 24-43 at baseline) than younger (aged 18-23 at baseline) adult twins, and were more stable among men than women. Heritabilities were significant at both baseline and follow-up for all three alcohol measures in both genders and both age groups, with a median magnitude of 0.48. Both longitudinal genetic and environmental covariances were significant, and both were generally higher among older pairs. Genetic covariances (median magnitude = 0.68) were significantly higher than environmental covariances (median = 0.36). Analyses of absolute changes in alcohol use revealed heritable influences on the disposition to change. We conclude that genes contribute to both consistency and change in patterns of alcohol use from early to midadulthood.

Adult↗
PubMed1988

Solubilization and purification of the lutropin (LH) receptor from porcine testes.

The LH receptor was solubilized from porcine testis homogenates by different detergents. Non-ionic detergents appeared to be the best ones regarding solubilization yield and recovery of active receptor after elution from hCG affinity gels. However, the final yield was not greater than 1-2% of the starting receptor activity. We also investigated the effect of added phospholipids (75% phosphatidylcholine + 25% phosphatidylethanolamine) on the yield of the overall purification process. It was shown that the best p value [i.e. the ratio of (detergent concentration - critical micellar concentration) to phospholipids] upon solubilization was congruent to 1.1 for a non-ionic detergent such as Nonidet P-40, while a higher p value was better upon elution. The stability of the solubilized receptor versus pH and SDS has been studied. The receptor exhibited two pKa's of denaturation congruent to 3.8 and 11.1, while the [125I]hCG-receptor complex dissociated with a pKa congruent to 3.8 and 10.3 SDS concentrations as low as 0.05% denatured rapidly and apparently, irreversibly, the solubilized LH receptor. The stability of different affinity gels was checked and it was found that the best yield for receptor elution (congruent to 10%) was obtained with an immunoaffinity anti-hCG support. The obtention of two monoclonal antibodies is mentioned, as well as their competition with the binding of [125I]pLH to testis homogenates.

Animals↗
PubMed2002

Rayleigh-Bénard convection with rotation at small Prandtl numbers.

We present experimental and theoretical results near the onset of the Rayleigh-Bénard convection with rotation about a vertical axis in a fluid with a Prandtl number sigma close to 0.18. In the experiment we used a H2-Xe gas mixture with a separation ratio Psi=0.22 and a Lewis number L=1.22 at various pressures and dimensionless rotation rates Omega up to 400. On the basis of a standard weakly nonlinear stability analysis, we found a supercritical, stationary bifurcation for Omega < than approximately 13, which became subcritical over the range 13 < than approximately Omega < or approximately 160. For Omega > than approximately 160 a supercritical Hopf bifurcation precedes the stationary instability of the uniform state. Following the unstable straight-roll fixed point in the subcritical regime by Galerkin methods we determined the location of the saddlenode and the stability of the nonlinear two-dimensional straight-roll state. The rolls were found to be unstable to three-dimensional Küppers-Lortz perturbations for 3.8 < than approximately Omega < than approximately 160. Theoretical results for a pure fluid with the same sigma were qualitatively similar. Measurements using shadowgraph flow visualization yielded a bifurcation line and an Omega range of subcriticality, which agreed with the stability analysis. In the subcritical range the experiment revealed a discontinuity of the pattern amplitude at onset, but was unable to find any hysteresis. Patterns at onset fluctuated irregularly between the ground state and the finite-amplitude state. In this parameter range the convection pattern further above onset was chaotically time dependent. Investigation of the Hopf bifurcation line was difficult because of a wall mode that, for large Omega, preceded the bulk instability. For Omega approximately equal to 400, patterns were found in the sample interior only when the expected Hopf bifurcation was exceeded by about 10%. This is consistent with the convective nature of the bifurcation. However, the observed structure, although time periodic, was spatially disordered and had a frequency that was considerably larger than the expected Hopf frequency. In a separate sample cell with a radial ramp in the spacing no structure was observed at all in the cell interior until the expected stationary instability was reached.

Journal Article↗
PubMed1998

Effect of replacing a conserved proline residue on the function and stability of bovine adrenodoxin.

A proline residue in the C-terminal part of the polypeptide chain is highly conserved among many [2Fe-2S] ferredoxins. To investigate the requirement for proline at this position, we constructed steric (4-108W), charged (4-108K), polar (4-108S) and non-polar (4-108A) truncated mutants of adrenodoxin and studied them for biological function and stability. Although the variants were expressed in Escherichia coli with a significantly lower yield compared with wild-type adrenodoxin, successful incorporation of the iron-sulfur cluster suggested their proper folding. Similar absorption, CD and EPR spectra indicated that the cluster environment was not affected by the mutations. No evidence for an essential role of Pro108 in determining the redox potential of adrenodoxin or its interactions with the redox partners was found. However, replacement of this residue results in a dramatic decrease in the overall protein stability. The differences in the Gibbs energy of unfolding at 37 degrees C, delta[delta(d)G(37 degrees C)], are -5.0, -7.8, -10.1 and -10.7 kJ/mol for 4-108A, 4-108S, 4-108W and 4-108K mutants, respectively, compared with 4-108P as a control. We conclude that the principle function of Pro108 is to stabilize adrenodoxin threefold: (i) through limitation of the conformation of the polypeptide chain in this region, (ii) through a hydrogen bond to Arg14 and (iii) favorable hydrophobic contacts.

Adrenodoxin↗
PubMed1979

Purification of mammalian tumor (L1210) thymidylate synthetase by affinity chromatography on stable biospecific adsorbent. Stabilization of the enzyme with neutral detergents.

Thymidylate synthetase from mouse leukemic L1210 cells was purified to electrophoretic homogeneity with 70% yield as a result of an affinity chromatography procedure based on reversible deoxyuridylate-dependent binding of the enzyme to a stable biospecific adsorbent, 10-formyl-5,8-dideazafolate, immobilized on aminoethyl-Sepharose. The presence of neutral detergents, Triton X-100, or Nonidet P40 stabilized thymidylate synthetase during purification. Analytical electrophoresis of the enzyme treated with an excess of 5-fluorodeoxyuridylate and 5,10-methylenetetrahydrofolate showed the presence of two forms of thymidylate synthetase--5-fluorodeoxyuridylate.5,10-methylenetetrahydrofolate complex, indicating that there are two binding sites for 5-fluorodeoxyuridylate present on the enzyme molecule. Molecular weight of native thymidylate synthetase was found to be 75,000, whereas that for the monomer was 38,500.

Animals↗
PubMedDate not supplied

[Oxidative stress and antioxidant cell protection systems in the microaerophilic bacterium Spirillum winogradskii].

The influence of oxygen availability during cultivation on the biosynthetic processes and enzymatic activities in the microaerophilic bacterium Spirillum winogradskii D-427 was studied, and the roles played by different systems of the defense against oxidation stress were determined. The metabolic adjustments caused by transition from microaerobic (2% O2) aerobic conditions (21% O2 of the gas phase) were found to slow down constructive metabolism and increase synthesis of exopolysaccharides as a means of external protection of cells from excess oxygen. This resulted in a twofold decline of the growth yield coefficient. Even though the low activity of catalase is compensated for by a multifold increase in the activities of other cytoplasmic enzymes protecting from toxic forms of O2--peroxidase and enzymes of the redox system of glutathione (glutathione peroxidase and glutathione reductase)--massive lysis of cells starts in the mid-exponential phase and leads to culture death in the stationary phase because of H2O2 accumulation in the periplasm (up to 10 micrograms/mg protein). The absence in cells of cytochrome-c-peroxidase, a periplasmic enzyme eliminating H2O2, was shown. It follows that the major cause of oxidative stress in cells is that active antioxidant defenses are located in the cytoplasm, whereas H2O2 accumulates in the periplasm due to the lack of cytochrome-c-peroxidase. The addition to the medium of thiosulfate promotes elimination of H2O2, stops cell lysis under aerobic conditions, lends stability to cultures, and results in a threefold increase in the growth yield.

Aerobiosis↗
PubMed1977

Effect of non-histone proteins on thermal transition of chromatin and of DNA.

The effect of chromatin non-histone protein on DNA and chromatin stability is investigated by differential thermal denaturation method. 1) Chromatin (rat liver) yields a multiphasic melting profile. The major part of the melting curve of this chromatin is situated at temperatures higher than pure DNA, with a distinct contribution due to nucleosomes melting. A minor part melts at temperatures lower than DNA which may be assigned to chromatin non-histone protein-DNA complex which destabilized DNA structure. 2) Heparin which extracts histones lowers the melting profile of chromatin and one observes also a contribution with a Tm lower that of pure DNA. In contrast, extraction on non-histone proteins by urea supresses the low Tm peak. 3) Reconstitution of chromatin non-histone protein-DNA complexes confirms the existence of a fraction of chromatin non-histone protein which lowers the melting temperature when compared to pure DNA. It is concluded that chromatin non-histone proteins contain different fractions of proteins which are causing stabilizing and destabilizing effect on DNA structure.

Animals↗
PubMed2003

Immobilization of thermolysin to polyamide nonwoven materials.

In the last few years, an increasing number of biotechnological techniques have been applied to the restoration and conservation of works of art, paintings, old maps, and papers or books. Enzymes can solve problems that give restorers difficulties, although for many applications it is not possible to use soluble enzymes; therefore, it is necessary to look for suitable carriers for immobilization. Different methods for covalent immobilization of enzymes to polyamide nonwovens were tested, using thermolysin as an example. Two distinct strategies were pursued: (1). controlled, partial hydrolysis of the polymer and subsequent binding of the enzyme to the released amino and carboxy groups; and (2). attachment of reactive groups directly to the polyamide without disintegrating the polymeric structure (O-alkylation). Different spacers were used for covalent fixation of the enzyme in both cases. The enzyme was fixed to the released amino groups by glutaraldehyde, either with or without a spacer. Either way, active enzyme could be immobilized to the matrix. However, intense treatment caused severe damage to the stability of the nonwoven fabric, and reduced the mechanical strength. Conditions were investigated to conserve the nonwoven fabric structure while obtaining near-maximum immobilized enzyme activity. Immobilization of the enzyme to the released carboxy group after acid hydrolysis was performed using dicyclohexylcarbodiimide. In comparison to the enzyme bound via the amino group, the yield of immobilized enzyme activity was slightly lower when benzidine was taken as spacer and still lower with a 1,6-hexanediamine spacer. O-alkylation performed with dimethylsulfate caused severe damage to the nonwoven fabric structure. Considerably better results were obtained with triethyloxonium tetrafluoroborate. As the spacers 1,6-hexanediamine and adipic acid dihydrazide were used, activation for immobilizing thermolysin was performed with glutaraldehyde, adipimidate, and azide. With the exception of azide, all combinations of spacers and activation reagents gave high yields of immobilized enzyme activity. Thermolysin immobilized by this technique showed a remarkably improved stability with respect to elevated temperature, extreme pH values, and reduced polarity. The nonwoven fabric can be stored for weeks without loss of enzyme activity by washing with distilled water and drying.

Drug Storage↗
PubMed1989

Stability of mandibular lengthening using bicortical screw fixation.

The mandibular lengthening procedure performed with the use of rigid internal fixation yields more stable results than previously demonstrated when nonrigid fixation is used. Twenty patients with Class II malocclusion who had undergone this procedure were examined retrospectively to assess postoperative skeletal change. The mean postoperative interval was 15.7 months. Although there was individual variability, no significant mean postoperative horizontal change was found, which indicated excellent stability.

Adolescent↗
PubMed1991

Relative activities and stabilities of mutant Escherichia coli tryptophan synthase alpha subunits.

In vitro mutagenesis of the Escherichia coli trpA gene has yielded 66 mutant tryptophan synthase alpha subunits containing single amino acid substitutions at 49 different residue sites and 29 double and triple amino acid substitutions at 16 additional sites, all within the first 121 residues of the protein. The 66 singly altered mutant alpha subunits encoded from overexpression vectors have been examined for their ability to support growth in trpA mutant host strains and for their enzymatic and stability properties in crude extracts. With the exception of mutant alpha subunits altered at catalytic residue sites Glu-49 and Asp-60, all support growth; this includes those (48 of 66) that have no enzymatic defects and those (18 of 66) that do. The majority of the enzymatically defective mutant alpha subunits have decreased capacities for substrate (indole-3-glycerol phosphate) utilization, typical of the early trpA missense mutants isolated by in vivo selection methods. These defects vary in severity from complete loss of activity for mutant alpha subunits altered at residue positions 49 and 60 to those, altered elsewhere, that are partially (up to 40 to 50%) defective. The complete inactivation of the proteins altered at the two catalytic residue sites suggest that, as found via in vitro site-specific mutagenesis of the Salmonella typhimurium tryptophan synthetase alpha subunit, both residues probably also participate in a push-pull general acid-base catalysis of indole-3-glycerol phosphate breakdown for the E. coli enzyme as well. Other classes of mutant alpha subunits include some novel types that are defective in their functional interaction with the other tryptophan synthetase component, the beta 2 subunit. Also among the mutant alpha subunits, 19 were found altered at one or another of the 34 conserved residue sites in this portion of the alpha polypeptide sequence; surprisingly, 10 of these have wild-type enzymatic activity, and 16 of these can satisfy growth requirements of a trpA mutant host. Heat stability and potential folding-rate alterations are found in both enzymatically active and defective mutant alpha subunits. Tyr-4. Pro-28, Ser-33, Gly-44, Asp-46, Arg-89, Pro-96, and Cys-118 may be important for these properties, especially for folding. Two regions, one near Thr-24 and another near Met-101, have been also tentatively identified as important for increasing stability.

Amino Acid Sequence↗
PubMed2005

Oxidation of methane over palladium catalysts: effect of the support.

This work is focused on the deep catalytic oxidation of methane over supported palladium catalysts. The influences of the metal loading, oxidation state of palladium, nature of supports, presence of promoters in the supports (for zirconia-based supports), and thermal stability have been studied experimentally. Catalysts were prepared by incipient wetness of commercially available supports with aqueous solutions of palladium nitrate. For gamma-alumina support, it was observed that the optimal amount of palladium is between 0.5% and 2%, with higher amounts leading to a loss in specific activity. Concerning the oxidation state of the catalyst, it is concluded that for all the supports tested in the present work, a reduction of the catalyst is not needed, yielding the same conversion at steady state catalysts reduced and oxidised. The thermal stability of various supported catalysts were also studied, zirconia supports being the most active. These supports, specially Y-modified zirconia support, do not suffer appreciable deactivation below 500 degrees C.

Air Pollution↗
PubMed2004

High stability of nuclear microsatellite loci during the early stages of somatic embryogenesis in Norway spruce.

Somatic embryos of Norway spruce (Picea abies (L.) Karst.) differentiate from proembryogenic masses (PEMs), which are subject to autodestruction through programmed cell death. In PEMs, somatic embryo formation and activation of programmed cell death are interrelated processes. We sought to determine if activation of programmed cell death in PEMs is caused by genetic aberrations during somatic embryogenesis. Based on the finding that withdrawal of auxin and cytokinin induces programmed cell death in PEMs, 1-week-old cell suspensions were cultured in medium either with or without auxin and cytokinin and then transferred to maturation medium containing abscisic acid. We analyzed the stability of three nuclear simple sequence repeat (SSR) microsatellite markers at successive stages of somatic embryogenesis in two cell lines. There were no mutations at the SSR loci at any of the successive developmental stages from PEMs to cotyledonary embryos, irrespective of whether or not the proliferation medium in which cell suspensions had been cultured contained auxin or cytokinin. The morphologies of plants regenerated from the cultures were similar, although withdrawal of auxin and cytokinin significantly stimulated the yield of both embryos and plants. We conclude, therefore, that the high genetic stability of somatic embryos in Norway spruce is unaffected by the induction of programmed cell death caused by withdrawal of auxin and cytokinin.

Cell Line↗
PubMed1998

DNA structure and fluctuations sensed from a 1.1ns molecular dynamics trajectory of a fully charged Zif268-DNA complex in water.

Molecular dynamics simulations of the zinc finger domain of protein Zif268, in a complex with a high affinity DNA sequence, yields a globally stable system with small yet significant readjustments with persistence time of the order of 1.1ns. The results confirm the quality of the standard GROMOS87 force field with a corrected solvent-to-solute interaction that does not affect the water-water SPC interactions nor the intra-molecular cohesive forces. Specificity determinants are discussed. The simulations of DNA alone, with the same force field, showed the important role played by the solvent and the symmetry of the counterion distribution. (Tapia & Velázquez, J. Am. Chem. Soc., 119, 5934, 1997) In the present work, this feature was retained when appropriate. The results for root mean square deviations and temperature B-factors illustrate the reliability of this approach. The structure of DNA is held by its interactions with the zinc finger protein. This behavior is not much affected by the slow whithering away of finger-1 from DNA. The factors contributing to the molecular stability found in GROMOS' potential energy function appear to be sufficient to yield stable fluctuation patterns when surrounding medium effects are properly included.

Computer Simulation↗
PubMed2006

Activation mapping as a percentage of local excitation: fMRI stability within scans, between scans and across field strengths.

Functional magnetic resonance imaging (fMRI) does not typically yield highly reproducible maps of brain activation. Maps can vary significantly even with constant scanning parameters and consistent task performance conditions (Liu et al., Magn. Reson. Med., 2004, 52:751-760). Reproducibility is even more of a problem when comparing fMRI signal magnitude and spatial extent of activation across scans involving different task performance levels, scan durations, pulse sequences or magnetic field strengths. In this report, the consistency of fMRI was reexamined by considering the relative spatial and temporal distribution of fMRI blood oxygen level dependent (BOLD) activation signals separately from the absolute magnitude of the activation signal in each brain area. Subjects repeatedly performed the same simple motor task but under a variety of imaging conditions, using both spiral and standard echo-planar pulse sequences and at 1.5- and 4.0-T magnetic field strengths. The results demonstrate that the absolute amplitude of BOLD statistical activation signals varied significantly across time and scanning conditions, but the relative spatial pattern of BOLD activation was highly reproducible across all conditions. Analysis of realistic simulated fMRI data sets indicates that stability of relative activation patterns could provide a useful tool for assessing the accuracy of fMRI maps.

Adult↗
PubMed1976

In vitro stabilization of a low-tin bone-imaging agent (99mTc-Sn-HEDP) by ascorbic acid.

The presence of oxidants in the 99mTc-pertechnetate and of oxygen in diagnostic kits containing low concentrations of Sn(II) has a detrimental effect upon in vitro and in vivo stability. Maintaining a nitrogen atmosphere or increasing the Sn(II) concentration inhibits the formation of 99mTcO4-. However, the latter remedy is likely to cause uptake in the reticuloendothelial system and has been associated with false positive or negative brain scans. We used ascorbic acid (an antioxidant) to ensure the in vitro stability with the low-Sn(II) bone agent disodium etidronate. In vitro stability studies by instant thin-layer chromatography, using high-acitivity generators and "instant pertechnetate," yielded less than 2% free pertechnetate at 24 hr after preparation. Distribution studies in guinea pigs show neither altered distribution of the bone agent nor abnormal distribution of ascorbic acid, suggesting its sole function as a noncomplexing stabilizer.

Animals↗