Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “modification”

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 1,297 records · Page 72Linked to original sources
PubMed1995

Self-initiated modification of hypertension treatment in response to perceived problems.

OBJECTIVE: To assess the prevalence of patient-initiated modification of drug instructions and the association between different classes of problems and the modification of hypertension therapy. DESIGN AND METHODS: In this cross-sectional study, all patients (n = 1215) who had been examined at a hypertension clinic during a 1-year period were surveyed. The response rate to the questionnaire was 85%. Of the 1035 respondents, 623 currently taking antihypertensive medication (self-report) were included in the study. RESULTS: Of the patients taking antihypertensive drugs, 36% admitted that they had tried to manage their condition with a lower dosage and/or fewer drugs than prescribed. The percentage of patients who modified their drug regimen decreased with increasing age. One or more problems with the treatment of hypertension were reported by 79% of the respondents. The odds ratio (95% confidence interval) for modification among patients who reported 1 or more problems compared with those not reporting any problem was 3.5 (2.12 to 5.67). The prevalence of modification increased with the number of problems; this was seen in all age groups and among men and women. CONCLUSIONS: Perceived problems in drug taking in the treatment of hypertension have an important impact on the prevalence of modifying drug instructions.

Adult↗
PubMed2001

The fission yeast COP9/signalosome is involved in cullin modification by ubiquitin-related Ned8p.

BACKGROUND: The function of the fission yeast cullins Pcu1p and Pcu4p requires modification by the ubiquitin-related peptide Ned8p. A recent report by Lyapina et al. shows that the COP9/signalosome (CSN), a multifunctional eight subunit complex, regulates Ned8p modification of Pcu1p. Disruption of caa1/csn1, which encodes subunit 1 of the putative S. pombe CSN, results in accumulation of Pcu1p exclusively in the modified form. However, it remained unclear whether this reflects global control of all cullins by the entire CSN complex. RESULTS: We demonstrate that multiple CSN subunits control Ned8p modification of Pcu3p, another fission yeast cullin, which, in complex with the RING domain protein Pip1p, forms a ubiquitin ligase that functions in cellular stress response. Pcu3p is modified by Ned8p on Lys 729 and accumulates exclusively in the neddylated form in cells lacking the CSN subunits 1, 3, 4, and 5. These CSN subunits co-elute with Pcu3p in gel filtration fractions corresponding to approximately 550 kDa and specifically bind both native and Ned8p-modified Pcu3p in vivo. While CSN does not influence the subcellular localization of Pcu3p, Pcu3p-associated in vitro ubiquitin ligase activity is stimulated in the absence of CSN. CONCLUSIONS: Taken together, our data suggest that CSN is a global regulator of Ned8p modification of multiple cullins and potentially other proteins involved in cellular regulation.

COP9 Signalosome Complex↗
PubMed2005

Targeted genome modification via triple helix formation.

Triplex-forming oligonucleotides (TFOs) that can bind to duplex DNA in a sequence-specific manner are potential tools to achieve targeted gene modification. Initial studies demonstrated the ability of TFOs to deliver mutagenic agents in a DNA site-specific manner. It has also been found that TFOs can induce gene modification in chromosomal DNA via the effect of the triple helix itself. Gene modification with TFOs includes induced recombination between a DNA target and a donor DNA molecule, a process that allows a TFO to exert an effect at a distance from the third-strand binding site. Ongoing efforts to develop chemical modifications on the third strand have increased the number of target sites possible for gene correction and new techniques for TFO delivery are beginning to enhance the biologic effectiveness of these reagents.

Animals↗
PubMed2003

Effect of surface modification on hydration kinetics of carbamazepine anhydrate using isothermal microcalorimetry.

The purpose of this research was to improve the stability of carbamazepine (CBZ) bulk powder under high humidity by surface modification. The surface-modified anhydrates of CBZ were obtained in a specially designed surface modification apparatus at 60 degrees C via the adsorption of n-butanol, and powder x-ray diffraction, Fourier-Transformed Infrared spectra, and differential scanning calorimetry were used to determine the crystalline characteristics of the samples. The hydration process of intact and surface-modified CBZ anhydrate at 97% relative humidity (RH) and 40 +/-C 1 degrees C was automatically monitored by using isothermal microcalorimetry (IMC). The dissolution test for surface-modified samples (20 mg) was performed in 900 mL of distilled water at 37 +/-C 0.5 degrees C with stirring by a paddle at 100 rpm as in the Japanese Pharmacopoeia XIII. The heat flow profiles of hydration of intact and surface-modified CBZ anhydrates at 97% RH by using IMC profiles showed a maximum peak at around 10 hours and 45 hours after 0 and 10 hours of induction, respectively. The result indicated that hydration of CBZ anhydrate was completely inhibited at the initial stage by surface modification of n-butanol and thereafter transformed into dihydrate. The hydration of surface-modified samples followed a 2-dimensional phase boundary process with an induction period (IP). The IP of intact and surface-modified samples decreased with increase of the reaction temperature, and the hydration rate constant (k) increased with increase of the temperature. The crystal growth rate constants of nuclei of the intact sample were significantly larger than the surface-modified sample's at each temperature. The activation energy (E) of nuclei formation and crystal growth process for hydration of surface-modified CBZ anhydrate were evaluated to be 20.1 and 32.5 kJ/mol, respectively, from Arrhenius plots, but the Es of intact anhydrate were 56.3 and 26.8 kJ/mol, respectively. The dissolution profiles showed that the surface-modified sample dissolved faster than the intact sample at the initial stage. The dissolution kinetics were analyzed based on the Hixon-Crowell equation, and the dissolution rate constants for intact and surface-modified anhydrates were found to be 0.0102 +/-C 0.008 mg(1/3) x min(-1) and 0.1442 +/-C 0.0482 mg(1/3) x min(-1). The surface-modified anhydrate powders were more stable than the nonmodified samples under high humidity and showed resistance against moisture. However, surface modification induced rapid dissolution in water compared to the control.

1-Butanol↗
PubMed2000

Post-translational modification of alphaB-crystallin of normal human lens.

The current study reports several post-translational modifications of alphaB-crystallin in normal human lenses. The isoforms of post-translational modified alphaB-crystallin were isolated from the normal human lenses of >70-age group by ion exchange chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The isoform modifications were determined in detail by fast atom bombardment mass spectroscopy and amino acid sequence analysis. As the criterion of non-modified alphaB-crystallin, alphaB-crystallin from 1-d-old infant lenses were used. The modifications found in this study involve oxidation of the N-terminal methionine-1 residue, phosphorylation of the serine-59 residue, and truncation of four amino acids from the C-terminal position of the crystallin. The oxidation of methionine-1 was found in the early stage of human life in 1-d-old lens, although other modification of alphaB-crystallin were usually only found in old lenses (>70-age group).

Amino Acid Sequence↗
PubMed2001

Does post-translational modification influence chaperone-like activity of alpha-crystallin? I. Study on phosphorylation.

It is difficult to isolate derivatives of alpha-crystallin with only one type of post-translational modification, because this protein is subjected to several different types of modification. In the present study using bovine lens proteins, we isolated mono-phosphorylated alphaB-crystallin with no other post-translational modifications. Using this material, we demonstrated that mono-phosphorylation reduced the activity of alphaB-crystallin by approximately 30%. Our results confirmed that investigation of the correlation between chaperone-like activities of alpha-crystallin and post-translational modification is important to understand the mechanism of cataract formation.

Animals↗
PubMed1995

Modification tolerability of soybean proglycinin.

Proglycinins containing multiple modifications, that is, with two kinds of single modifications, designed previously to improve food functions, were assessed for ability to form proper conformations. This was done to discover the modification tolerability of proglycinin. Based on our results, three new criteria are proposed for judging formation of proper conformations. Our results suggest that proglycinin molecules tolerate different combinations of single modifications without misfolding.

Amino Acid Sequence↗
PubMed1998

Chemical modification of the hemolytic lectin CEL-III by succinic anhydride: involvement of amino groups in the oligomerization process.

CEL-III is a Ca(2+)-dependent lectin from a marine invertebrate, Cucumaria echinata, which shows strong hemolytic activity toward human and rabbit erythrocytes. After binding to carbohydrate receptors, CEL-III oligomerizes in the erythrocyte membrane to form ion-permeable pores, leading to the colloid osmotic rupture of the cells. Since hemolysis was greatly increased in the alkaline pH, especially above pH 9, involvement of amino groups of CEL-III in its hemolytic activity was evaluated using chemical modification by succinic anhydride. After modification of 7 amino groups per protein molecule, the hemolytic activity of CEL-III was reduced to 23% of the native protein, but hemagglutinating and carbohydrate-binding activities were only slightly affected even after modification of 14 amino groups. A circular dichroism spectrum of modified CEL-III showed almost no change in the secondary structure from that of the native protein, indicating that the decrease of hemolytic activity was not caused by partial unfolding of the protein. Immunoblotting analysis of the erythrocyte membrane treated with modified CEL-III showed a decrease in the formation of CEL-III oligomer in the membrane in parallel with the decrease in hemolytic activity. These results suggest that amino groups of CEL-III are involved in its oligomerization in the cell membrane, and their modification leads to inactivation of the protein without much influence on the carbohydrate-binding activity.

Amino Acids↗
PubMed2006

[Research advances on the relationship of PI3-kinase/Akt/mTOR pathway and epigenetic modification].

The mammalian target of rapamycin (mTOR) has been shown to link growth factor signaling and posttranscriptional control of protein translation through activation of the PI3K/Akt pathway, which is frequently involved in cell cycle progression. The inhibition of mTOR has promising potential in anticancer and immunosuppressive therapies, and additional phase II clinical trials are ongoing. Epigenetic modification, which involves DNA methylation, histone modification and chromatin remodeling, as well as the recently described RNAi mechanism, can initiate the formation of silenced chromatin. Persistent activation or inhibition of the mTOR pathway may affect epigenetic modification. In this paper, we reviewed the research advances in the relationship between PI3K/Akt/mTOR and epigenetic modification.

Animals↗
PubMed1994

Robust, noniterative, and computationally efficient modification of van Cittert deconvolution optical figuring.

A modification of van Cittert deconvolution (VCD) is introduced and shown to yield a robust, noniterative (or closed-form), and numerically efficient method of deconvolution. This modification removes the restrictions limiting the applicability of conventional VCD only to shapes and relative positions of the convolved functions for which it converges, while also avoiding the ill effects of zeros in these functions. The resulting method is computationally efficient because it is noniterative and uses the fast Fourier transform. In contrast to the convergences obtained with VCD, those obtained with this modified method are ensured by their expansion in terms of an introduced auxiliary function rather than the convolved functions. This permits both the general removal of the above limitations and arbitrarily accurate deconvolution of infinitely sampled input data even in the presence of input data noise. For discretely sampled input data the accuracy of this modification is shown to be limited only by the implicit bandwidth of the input data density. To exemplify its numerical and analytical advantages, I apply the method to computer control of optical surface figuring. I also demonstrate an intrinsic means of optimal frequency filtering of raw input data made available by this modification. The advantages of this procedure are also applicable to image restoration.

Computer Simulation↗
PubMed2006

Analyzing histone modification using crosslinked chromatin treated with micrococcal nuclease.

Epigenetic processes involve alterations in the covalent modification of histones, which are driven by sequence-specific transcription factors recruiting the enzymatic machinery performing these reactions. Such histone modifications alter the charge or biochemical surface of the chromatin fiber and also serve as "docking" sites for transcription factor and chromatin remodelling complexes. Examining histone modification patterns is vital if we want to understand how transcription complexes establish patterns of gene expression. Histone modification can be quite localized and sometimes only involves a few nucleosomes. We therefore established a chromatin immunoprecipitation procedure that uses crosslinked chromatin allowing the isolation of small chromatin fragments while simultaneously minimizing histone movement during chromatin preparation.

Animals↗
PubMed2006

Activity-dependent bidirectional modification of inhibitory synaptic transmission in rat subthalamic neurons.

Rebound burst activity can be generated in neurons in the subthalamic nucleus (STN) by strong GABAergic inhibitory inputs from the globus pallidus externa (GPe) that is reciprocally connected with the STN. It has been proposed that the rebound burst activity in STN neurons is a key event for generating synchronized rhythmic burst activity in the GPe-STN loop, which may be relevant to the resting tremor in Parkinson's disease. Here we report that rebound burst firing of STN neurons induces long-lasting bidirectional modifications of GABAergic synaptic transmission in STN neurons themselves. Using the gramicidin perforated-patch clamp technique in the brain slice preparation, we recorded IPSPs from STN neurons during electrical stimulation of the internal capsule. Rebound spikes triggered by hyperpolarizing current pulses were used to induce modification of inhibitory synaptic transmission. We found that long-lasting potentiation of IPSPs could be induced in the neurons exhibiting three or more rebound spikes that had interspike intervals shorter than half of those during base spontaneous activity, whereas long-lasting depression or no change of IPSP amplitude was likely to be observed in neurons that had no rebound burst or two rebound spikes within a burst. The potentiation or depression of IPSPs was associated with a negative or positive shift of reversal potential of IPSPs (E(IPSP)). The modifications of IPSPs were dependent on activation of postsynaptic voltage-gated calcium channels. This study is the first demonstration that activity-dependent bidirectional modifications of inhibitory synaptic transmission are attributable to bidirectional shifts of E(IPSP).

Action Potentials↗
PubMed2006

Structural stabilization and functional improvement of horseradish peroxidase upon modification of accessible lysines: experiments and simulation.

Horseradish peroxidase (HRP) is an important heme enzyme with enormous medical diagnostic, biosensing, and biotechnological applications. Thus, any improvement in the applicability and stability of the enzyme is potentially interesting. We previously reported that covalent attachment of an electron relay (anthraquinone 2-carboxylic acid) to the surface-exposed Lys residues successfully improves electron transfer properties of HRP. Here we investigated structural and functional consequences of this modification, which alters three accessible charged lysines (Lys-174, Lys-232, and Lys-241) to the hydrophobic anthraquinolysine residues. Thermal denaturation and thermoinactivation studies demonstrated that this kind of modification enhances the conformational and operational stability of HRP. The melting temperature increased 3 degrees C and the catalytic efficiency enhanced by 80%. Fluorescence and circular dichroism investigations suggest that the modified HRP benefits from enhanced aromatic packing and more buried hydrophobic patches as compared to the native one. Molecular dynamics simulations showed that modification improves the accessibility of His-42 and the heme prosthetic group to the peroxide and aromatic substrates, respectively. Additionally, the hydrophobic patch, which functions as a binding site or trap for reducing aromatic substrates, is more extended in the modified enzyme. In summary, this modification produces a new derivative of HRP with enhanced electron transfer properties, catalytic efficiency, and stability for biotechnological applications.

Binding Sites↗
PubMed2001

A simple modification of the Baermann method for diagnosis of strongyloidiasis.

The diagnosis of Strongyloides stercoralis infections is routinely made by microscopic observation of larvae in stool samples, a low sensitivity method, or by other, most effective methods, such as the Baermann or agar culture plate methods. We propose in this paper a practical modification of Baermann method. One hundred and six stool samples from alcoholic patients were analyzed using the direct smear test, agar culture plate method, the standard Baermann method, and its proposed modification. For this modification the funnel used in the original version of the method is substituted by a test tube with a rubber stopper, perforated to allow insertion of a pipette tip. The tube with a fecal suspension is inverted over another tube containing 6 ml of saline solution and incubated at 37 degrees C for at least 2 h. The saline solution from the second tube is centrifuged and the pellet is observed microscopically. Larva of S. stercoralis were detected in six samples (5.7%) by the two versions of the Baermann method. Five samples were positive using the agar culture plate method, and only in two samples the larva were observed using direct microscopic observation of fecal smears. Cysts of Endolimax nana and Entamoeba histolytica/dyspar were also detected in the modification of Baermann method. Data obtained by the modified Baermann method suggest that this methodology may helps concentrate larvae of S. stercoralis as efficiently as the original method.

Agar↗
PubMed2005

Increased parathyroid hormone gene expression in secondary hyperparathyroidism of experimental uremia is reversed by calcimimetics: correlation with posttranslational modification of the trans acting factor AUF1.

Most patients with chronic kidney disease develop secondary hyperparathyroidism with disabling systemic complications. Calcimimetic agents are effective tools in the management of secondary hyperparathyroidism, acting through allosteric modification of the calcium-sensing receptor (CaR) on the parathyroid gland (PT) to decrease parathyroid hormone (PTH) secretion and PT cell proliferation. This study showed that rats that were fed an adenine high-phosphorus diet had increased serum PTH and PTH mRNA levels at 7 and 21 d. For studying the effect of activation of the CaR by the calcimimetics R-568 on PTH gene expression, R-568 was given by gavage to uremic rats for the last 4 d of a 7-d adenine high-phosphorus diet. R-568 decreased both PTH mRNA and serum PTH levels. The effect of the calcimimetic on PTH gene expression was posttranscriptional and correlated with differences in protein-RNA binding and posttranslational modifications of the trans acting factor AUF1 in the PT. The AUF1 modifications as a result of uremia were reversed by treatment with R-568 to those of normal rats. Therefore, uremia and activation of the CaR mediated by calcimimetics modify AUF1 posttranslationally. These modifications in AUF1 correlate with changes in protein-PTH mRNA binding and PTH mRNA levels.

Aniline Compounds↗
PubMed1972

Teaching behavior modification to nonprofessionals.

Two instructional methods (role playing and lecture) were compared in evaluating the effectiveness of teaching behavior modification to institutional attendants. Pre- and post-test measures were obtained for two major outcome variables: (1) knowledge of behavior modification principles and (2) ratings of ability to apply behavior modification techniques. Results indicated that role playing was more effective in teaching behavior modification skills while the lectures were more effective in teaching principles of behavior modificaiton.

Journal Article↗
PubMed1982

Training teachers in generalized writing of behavior modification programs for multihandicapped deaf children.

In contrast to previous studies where teachers were instructed how to implement behavior modification programs designed by an experimenter, teachers in the present experiment were taught how to write as well as implement behavior modification programs. The generalized effects of two training conditions on teacher and pupil behaviors were assessed by a multiple baseline design where, following baseline, two teachers of multi-handicapped deaf children were taught to set objectives and measure pupil performance (measurement training), Later, through a training manual, they learned a general problem-solving approach to writing behavior modification programs (programming training). After both training conditions, experimenter feedback was given for teachers' application of training to a target behavior for one pupil and generalization was measured across target behaviors for the same pupil and across pupils. It was found that measurement training had little general effect on either teacher behavior or pupil behavior. However, after programming training, teachers increased their program writing and correct use of behavior modification procedures and generalized this training across pupils and target behaviors. Along with these effects, there was improvement in pupil behaviors. Possible explanation for generalized effects of teacher training were considered.

Adult↗
PubMed2004

Color-pattern modifications and speciation in butterflies of the genus Vanessa and its related genera Cynthia and Bassaris.

We have previously shown that the systemic injection of sodium tungstate, a protein-tyrosine phosphatase (PTPase) inhibitor, to pupae immediately after pupation efficiently produces characteristic color-pattern modifications on the wings of many species of butterflies including Vanessa indica and Cynthia cardui. In these species, the black spots reduced in size in response to the treatment. Similar modifications are occasionally seen in the field-caught aberrant individuals. Exceptionally, however, a C. cardui individual with enlarged black spots ("reversed" modification pattern) has been reported. Here we show that these modified patterns of V. indica and C. cardui are quite similar to the normal color-patterns of other Vanessa species. V. indica with tungstate-induced modifications resembled V. tameamea, V. samani, and Bassaris itea, whereas V. dilecta, V. atalanta, and V. dejeanii are similar to the "reversed" individual. Most features seen in the experimentally-modified V. indica were observed throughout the fore- and hindwings of V. samani. In contrast, the experimentally-induced color-patterns of C. cardui did not parallel variation of Cynthia butterflies. Since it has been proposed that a hypothetical transduction pathway with a PTPase for the scale-cell differentiation globally coordinates the wing-wide color-patterns, our findings suggest that spontaneous mutations in genes in this hypothetical pathway might have played a major role in creating new color-patterns and species in the Vanessa genus but not in the Cynthia genus. This evolutionary mechanism may probably be shared more widely in Lepidoptera, although this would not be a sole determinant for the color-pattern development and evolution.

Animals↗