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Weight loss after dieting with behavioral modification for obesity: the predicting efficiency of some psychometric data.

The aim of the study was to identify the predicting efficiency of some psychometric data on weight loss after behavior modification in moderately obese patients. A group of patients on a weight loss program with a moderately hypoenergetic diet plus behavior modification therapy for 24 weeks completed the Eating Inventory (EI), the Eating Disorder Inventory (EDI), the Body Shape Questionnaire (BSQ) and the Body Attitude Questionnaire (BAQ). Correlations between the pre-diet and post-treatment scores were evaluated by stepwise regression analysis. The weight loss percentage was positively correlated with the EDI Bulimia scale and the BAQ Feeling Fat, and negatively with the EDI Body Dissatisfaction and Interpersonal Distrust scores. These findings indicate the true effectiveness of the behavior modification technique employed to extinguish bulimic behaviors. Furthermore, it can be suggested that realistic attitudes towards own fatness with a strong motivation and a good relationship with the therapist guarantee a greater weight loss.

Adult↗

Adaptive modifications of human postsaccadic pursuit eye movements induced by a step-ramp-ramp paradigm.

The main purpose of the present study was to investigate adaptive properties in human smooth-pursuit eye movements generated by a peripheral moving target. In adaptation trials, a target appeared in the peripheral visual field and immediately moved away at a constant speed, and a subject made a saccade and postsaccadic pursuit responses to track it. The target speed was, however, changed to a higher or lower constant speed (step-ramp-ramp target motion) at the termination of the saccade. This adaptation paradigm induced adaptive modifications in postsaccadic pursuit responses and our results revealed the following properties of the pursuit adaptation system. TOPOGRAPHIC MODIFICATION: Modification of the initial pursuit velocity depends on the position of a moving target. PURSUIT GAIN CHANGE: Pursuit velocity is modified not by the addition of a constant bias to the pre-adaptation pursuit velocity, but by a change in the pursuit gain (pursuit velocity/target velocity). LACK OF INFLUENCE ON SACCADE PROPERTIES: Pursuit adaptation does not change the amplitude and latency of saccades either to a moving target or to a stationary target.

Adaptation, Physiological↗

Conotoxins and the posttranslational modification of secreted gene products.

The venoms of predatory cone snails (genus Conus) have yielded a complex library of about 50-100,000 bioactive peptides, each believed to have a specific physiological target (although peptides from different species may overlap in their target specificity). Conus has evolved the equivalent of a drug development strategy that combines the accelerated evolution of toxin sequences with an unprecedented degree of posttranslational modification. Some Conus venom peptide families are the most highly posttranslationally modified classes of gene products known. We review the variety and complexity of posttranslational modifications documented in Conus peptides so far, and explore the potential of Conus venom peptides as a model system for a more general understanding of which secreted gene products may have modified amino acids. Although the database of modified conotoxins is growing rapidly, there are far more questions raised than answers provided about possible mechanisms and functions of posttranslational modifications in Conus.

Amino Acid Sequence↗

[The isolated rabbit heart: comparison between five different modifications].

BACKGROUND: The isolated heart as an experimental model has been firmly established for more than 100 years. MATERIAL AND METHODS: In this study, five modifications are compared: 1. modified Langendorff apparatus (LA) with modified Krebs-Henseleit (KH) solution a) not containing bovine serum albumin (BSA; n = 13) and b) containing BSA (n = 16), 2. LA with KH solution containing BSH and bovine erythrocytes (n = 14), 3. LA with support rabbit (n = 6), and 4. "working heart" preparation with KH solution, BSA and bovine erythrocytes (n = 16). In the latter modification, no balloon was inserted into the left ventricular cavity, i. e., systemic and coronary circuits were not separated from each other. After completion of the preparation and 20-min stabilization, hemodynamic and metabolic data were assessed while the hearts were contracting in the ejecting mode. Thereafter, protocols for different studies were performed that are not presented here. However, the stability of the modifications within their individual protocols is reported. RESULTS: The results suggest that hearts perfused with KH solution are well suited for short protocols. In spite of the additional costs and time, blood perfusion is required for long-lasting protocols or if changes in coronary flow are to be investigated. CONCLUSIONS: The working heart exhibits both the best function and stability at a relatively low experimental expenditure. Yet, it is not suited for studies where perfusion pressure needs to be changed independent of arterial pressure.

Animals↗

Methanethiosulfonate-modification alters local anesthetic block in rNav1.4 cysteine-substituted mutants S1276C and L1280C.

We previously showed that lysine substitutions at two residues in segment 6 of domain 3 in voltage-gated Na(+) channel rNav1.4 (S1276K, L1280K) reduced steady-state inactivated local anesthetic block. Here we studied cysteine substitutions at the same residues (S1276C, L1280C). We used whole-cell recordings to determine local anesthetic block (100 microM bupivacaine) before and after cysteine modification with 1.5 mM 2-aminoethyl methanethiosulfonate (MTSEA). Compared with rNav1.4, steady-state resting bupivacaine block at -180 mV was increased in S1276C, while inactivated block at -50 mV was not different in the mutants. After application of MTSEA at -160 mV, rNav1.4 showed enhanced bupivacaine block and a negative shift in V(1/2) of the bupivacaine affinity curve, while L1280C and S1276C showed a decrease in inactivated bupivacaine block after MTSEA. Application of MTSEA at 0 mV produced similar results in rNav1.4 and L1280C, but an opposite effect in S1276C, i.e., enhancement of bupivacaine block, with a large negative shift in V(1/2) of the bupivacaine affinity curve similar to that found in rNav1.4. We conclude that 1) MTSEA modification of 1276C or 1280C decreases inactivated bupivacaine block similar to that found in L1280K and S1276K, 2) residue 1276C is only accessible to MTS-modification in the resting state, and 3) MTSEA may modify a native cysteine in rNav1.4 that produces an allosteric, indirect effect on bupivacaine affinity.

Anesthetics, Local↗

Chemical and photochemical modification of colicin E1 and gramicidin A in bilayer lipid membranes.

Chemical modification and photodynamic treatment of the colicin E1 channel-forming domain (P178) in vesicular and planar bilayer lipid membranes (BLMs) was used to elucidate the role of tryptophan residues in colicin E1 channel activity. Modification of colicin tryptophan residues by N-bromosuccinimide (NBS), as judged by the loss of tryptophan fluorescence, resulted in complete suppression of wild-type P178 channel activity in BLMs formed from fully saturated (diphytanoyl) phospholipids, both at the macroscopic-current and single-channel levels. The similar effect on both the tryptophan fluorescence and the electric current across BLM was observed also after NBS treatment of gramicidin channels. Of the single-tryptophan P178 mutants studied, W460 showed the highest sensitivity to NBS treatment, pointing to the importance of the water-exposed Trp460 in colicin channel activity. In line with previous work, the photodynamic treatment (illumination with visible light in the presence of a photosensitizer) led to suppression of P178 channel activity in diphytanoyl-phospholipid membranes concomitant with the damage to tryptophan residues detected here by a decrease in tryptophan fluorescence. The present work revealed novel effects: activation of P178 channels as a result of both NBS and photodynamic treatments was observed with BLMs formed from unsaturated (dioleoyl) phospholipids. These phenomena are ascribed to the effect of oxidative modification of double-bond-containing lipids on P178 channel formation. The pronounced stimulation of the colicin-mediated ionic current observed after both pretreatment with NBS and sensitized photomodification of the BLMs support the idea that distortion of membrane structure can facilitate channel formation.

Bromosuccinimide↗

Poly(ethylene glycol) modification of beta-glucuronidase-antibody conjugates for solid-tumor therapy by targeted activation of glucuronide prodrugs.

Methoxypoly(ethylene glycol) (PEG) modification of Escherichia coli beta-glucuronidase (betaG) was examined as a method to improve the stability and pharmacokinetics of antibody-betaG conjugates for the targeted activation of glucuronide prodrugs at tumor cells. Introduction of 3 PEG molecules did not affect betaG activity whereas higher degrees of PEG modification produced progressively greater loss of enzymatic activity. The enzyme was found to be stable in serum regardless of PEG modification. PEG-modified betaG was coupled via a thioether bond to mAb RH1, an IgG2a antibody that binds to the surface of AS-30D hepatoma cells, to produce conjugates with 3 (RH1-betaG-3PEG), 5.2 (RH1-betaG-5PEG) or 9.8 (RH1-betaG-10PEG) PEG molecules per betaG with retention of 75%, 45% and 40% of the combined antigen-binding and enzymatic activity of the unmodified conjugate RH1-betaG. In contrast to the rapid serum clearance of RH1-betaG observed in mice, the PEG-modified conjugates displayed extended serum half-lives. RH1-betaG-3PEG and RH1-betaG-5PEG also exhibited reduced spleen uptake and greater tumor accumulation than RH1-betaG. BHAMG, the glucuronide prodrug of p-hydroxyaniline mustard (pHAM), was relatively nontoxic in vivo. Injection of 6 mg/kg or 12 mg/kg pHAM i.v. depressed white blood cell numbers by 46% and 71% whereas 80 mg/kg BHAMG reduced these levels by 22%. Although the tumor/blood ratio of RH1-betaG-5PEG was adversely affected by slow clearance from serum, combined therapy of small solid hepatoma tumors with this conjugate, followed 4 and 5 days later with i.v. injections of BHAMG, cured all of seven mice with severe combined immunodeficiency. Combined treatment with a control antibody-betaG conjugate and BHAMG delayed tumor growth and cured two of six mice while treatment with pHAM or BHAMG alone was ineffective.

Aniline Mustard↗

Evaluation of intrahepatic perfusion on fusion imaging using a combined CT/SPECT system: influence of anatomic variations on hemodynamic modification before installation of implantable port systems for hepatic arterial infusion chemotherapy.

BACKGROUND: In some patients with hepatic tumors, anatomic variations in the hepatic arteries may require hemodynamic modification to render effective hepatic arterial infusion chemotherapy delivered via implantable port systems. We used a combined CT/SPECT system to obtain fused images of the intrahepatic perfusion patterns in patients with such anatomic variations and assessed their effects on the treatment response of hepatic tumors. METHODS: Using a combined SPECT/CT system, we obtained fused images in 110 patients with malignant liver tumors (n = 75) or liver metastasis from unresectable pancreatic cancer (n = 35). Patients with anatomic hepatic arteries variations underwent hemodynamic modification before the placement of implantable port systems for hepatic arterial infusion chemotherapy. We evaluated their intrahepatic perfusion patterns and the initial treatment response of their liver tumors. The perfusion patterns on the fused images were classified as homogeneous, local hypoperfusion, and/or perfusion defect. Using the WHO criteria of complete response (CR), partial response (PR), no change (NC), and progressive disease (PD), we evaluated the patients' tumor responses after 3 months on multislice helical CT scans. The treatment was regarded as effective in patients who achieved a complete response or partial response. RESULTS: Anatomic hepatic artery variations were present in 15 of the 110 patients (13.6%); 5 manifested replacement of the left hepatic artery (LHA), 8 of the right hepatic artery (RHA), and 1 each had replacement of the RHA and LHA, and replacement of the LHA plus an accessory RHA. In 13 of these 15 patients (87%), occlusion with metallic coils was successful. On fusion imaging, the perfusion patterns were recorded as homogeneous in 6 patients (43%), as hypoperfusion in 7 (50%), and 1 patient had a perfusion defect (7.1%) in the embolized arterial region. Of the 8 patients with RHA replacement, 4 manifested a homogeneous distribution and 3 hypoperfusion. In 2 of 5 patients with LHA replacement, the distribution was homogeneous. In 1 patient with RHA and LHA replacement, and in 1 patient with LHA replacement and an accessory RHA, we noted hypoperfusion in the RHA territory. All 6 patients with homogeneous distribution were classified as PR or NC on follow-up multidetector CT. Of the 7 patients manifesting hypoperfusion, 3 were classified as PD (43%), 3 as NC (43%), and 1 as PR (14%) on follow-up CT. CONCLUSION: Hemodynamic modification of anatomic hepatic artery variations resulted in hypoperfusion on fusion images. Differences in the intrahepatic perfusion patterns may affect the response to hepatic arterial infusion chemotherapy.

Adult↗

Principal modifications of the Duhamel procedure in the treatment of Hirschsprung's disease. Analysis based on results of an international retrospective study of 2,430 patients.

In the literature, many articles refer to the DUHAMEL technique or some of its modifications in the treatment of Hirschsprung's disease, however, no complete review of all of them has been published to date. The authors present an analysis of the principal modifications of this technique based on the results of an international retrospective survey that evaluated a series of 2,430 patients as well as data from the literature. The important role of the internal anal sphincter in the physiology of continence is emphasized; understanding its function is an imperative prerequisite for a successful Duhamel procedure. The original technique, which used two crushing Kocher clamps as proposed by Duhamel in 1956, as well as a majority of the modifications with various spur-crushing instruments are no longer in use. At present, surgeons generally use staplers for the colorectal anastomosis.

Anastomosis, Surgical↗

Alpha-synuclein structure, posttranslational modification and alternative splicing as aggregation enhancers.

Alpha-synuclein aggregation is thought to be a key event in the pathogenesis of synucleinopathies. Although different alpha-synuclein alterations and modifications have been proposed to be responsible for early aggregation steps, the mechanisms underlying these events remain unclarified. Alpha-synuclein is a small protein localized to synaptic terminals and its intrinsic structure has been claimed to be an important factor for self-oligomerization and self-aggregation. Alpha-synuclein expression studies in cell cultures have demonstrated that posttranslational modifications, such as phosphorylation, oxidation, and sumoylation, are primarily involved in alpha-synuclein aggregation. Furthermore, in the last few years accumulating evidence has pointed to alternative splicing as a crucial mechanism in the development of neurodegenerative disorders. At least three different alpha-synuclein isoforms have been described as products of alternative splicing. Two of these isoforms (alpha-synuclein 112 and alpha-synuclein 126) are shorter proteins with probably altered functions and aggregation propensity. The present review attempts to summarize the data so far available on alpha-synuclein structure, posttranslational modifications, and alternative splicing as possible enhancers of aggregation.

Alternative Splicing↗

Local modification of benthic flow environments by suspension-feeding stream insects.

Larval black flies often exhibit spatially aggregated distributions, and individuals within patches can potentially reduce the supply of suspended food particles to downstream neighbors by modifying local flow characteristics. We used hot-film anemometry to quantify the magnitude and spatial extent of flow modifications downstream from feeding Simulium vittatum larvae in a laboratory flume, and to determine whether temporal patterns of flow variation are related to movements of the larval feeding appendages. Mean velocity 1 mm downstream from feeding larvae was reduced by 75%, and the percent reduction in velocity diminished asymptotically with downstream distance. Reduced velocities were evident as much as 60 mm downstream from, and 3 mm to either side of, larvae. Turbulence intensity (i.e., the SD of the velocity time series) was generally higher in this region relative to control flow conditions. Three results demonstrate the major contribution of the larval feeding appendages (i.e., labral fans) to such flow modification. First, there was a minimal reduction in mean velocity 5 mm downstream from non-feeding larvae (i.e., with closed labral fans), whereas mean velocity at the same location was reduced markedly when larvae were feeding. Second, the power spectrum of the velocity time series exhibited greatest power at frequencies that corresponded to the frequency of labral fan motions. Third, fan flick times accounted for most of the variance in the velocity power spectrum. The large local flow modifications that we documented have potentially important consequences for the feeding performance and growth of individuals located within larval aggregations, and are likely to influence behavioral interactions and spacing patterns.

Animals↗

Cytochrome b561 is not fatty acylated but acetylated at amino terminus in chromaffin vesicle membranes: an approach for the identification of posttranslational modification of transmembrane proteins.

We examined the nature of the posttranslational modification of bovine cytochrome b(561), a membrane-spanning protein and an essential component of neuroendocrine secretory vesicles. Matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOF-MS) showed two populations in the partially digested fragments of cytochrome b(561), which were obtained by controlled treatment of cytochrome b(561)-proteoliposomes with trypsin. One population, containing the posttranslationally modified amino-terminal region, showed molecular masses which were by about 40 Da larger than the theoretical molecular masses. The other population, without the modified amino-terminal region, showed a reasonable matching with the theoretical masses. This result suggested that the posttranslational modification occurred only in the amino-terminal region. The amino-terminal peptide was isolated by tryptic peptide mapping followed by treatment with acylamino-acid-releasing enzyme. Amino acid sequence and MALDI-TOF-MS analyses of the amino-terminal peptide showed that the initial Met residue was acetylated. There was no other posttranslational modification in the amino-terminal region, such as covalent fatty acylation through an ester linkage to Ser or Thr residues.

Acylation↗

Automatic measurement of polyethylene modification in metal-backed artificial hip joints using three-dimensional CT.

A new method has been developed for automatic measurement of polyethylene linear modification using three-dimensional CT in total hip arthroplasty (THA) and bipolar hemiarthroplasty (BHP). We obtained a three-dimensional digital image of the metal components by widening the maximum window width, adjusting the proper cutoff threshold level, and removing the metal artifact. The centric coordinates of both the metal-backed cup and the femoral head were calculated from this image. Modification was defined as a change in distance between those two points from their original interval. Phantom studies of the accuracy and reproducibility of the method indicated that the average error ranged from 0.02 to 0.12 mm and the standard deviation ranged from 0.01 to 0.05 mm. Clinical in vivo measurement was performed without error of computer software on 19 hips in which modification of highly cross-linked polyethylene components was significantly large.

Artifacts↗

Clinical implementation of the IHE presentation of grouped procedures integration profile in a multivendor environment--workflow modification and barriers to implementation.

The implementation of presentation of grouped procedures (PGP) integration profile, as described in the Integrating the Healthcare Enterprise (IHE) Technical Framework, on computed tomography (CT) and magnetic resonance (MR) scanners as well as the picture archiving communication system (PACS) addresses the problem faced by many institutions in which there are multiple-requested procedures performed in one acquisition. It is a solution that, just like the initial implementation of PACS, requires substantial modification to workflow. Implementation of PGP not only speeds access to relevant images for the requested procedure, it reduces network traffic and is less demanding on workstation hardware because of the smaller data sets transmitted. These workflow issues show that PGP implementation is not complete when the vendors install the necessary hardware and software modifications. This report discusses the workflow modifications and the barriers to implementing the PGP solution.

Data Display↗

The telomere-binding protein Taz1p as a target for modification by a SUMO-1 homologue in fission yeast.

In fission yeast (Schizosaccharomyces pombe) the homologue of the mammalian SUMO-1 ubiquitin-like modifier is encoded by the pmt3 gene. A two-hybrid screen using the telomere-binding protein Taz1p as bait identified Pmt3p as an interacting factor. In vitro experiments using purified components of the fission yeast Pmt3p modification system demonstrated that Taz1p could be modified directly by Pmt3p. The amino acid sequence of Taz1p contains a close match to the consensus modification site for SUMO-1, and a PEST sequence similar to those found in established SUMO-1 targets. Although previous experiments have identified an increase in telomere length as one consequence of the pmt3--genotype, we could not detect Pmt3p modification of Taz1p in protein extracts made from exponentially growing haploid cells or any effect of Pmt3p on the localization of GFP-Taz1p at discrete foci in the haploid cell nucleus.

Repressor Proteins↗

Histone modification and the control of heterochromatic gene silencing in Drosophila.

Covalent modifications of histones index structurally and functionally distinct chromatin domains in eukaryotic nuclei. Drosophila with its polytene chromosomes and developed genetics allows detailed cytological as well as functional analysis of epigenetic histone modifications involved in the control of gene expression pattern during development. All H3K9 mono- and dimethylation together with all H3K27 methylation states and H4K20 trimethylation are predominant marks of pericentric heterochromatin. In euchromatin, bands and interbands are differentially indexed. H3K4 and H3K36 methylation together with H3S10 phosphorylation are predominant marks of interband regions whereas in bands different H3K27 and H4K20 methylation states are combined with acetylation of H3K9 and H3K14. Genetic dissection of heterochromatic gene silencing in position-effect variegation (PEV) by Su(var) and E(var) mutations allowed identification and functional analysis of key factors controlling the formation of heterochromatin. SU(VAR)3-9 association with heterochromatic sequences followed by H3K9 methylation initiates the establishment of repressive SU(VAR)3-9/HP1/SU(VAR)3-7 protein complexes. Differential enzymatic activities of novel point mutants demonstrate that the silencing potential of SU(VAR)3-9 is mainly determined by the kinetic properties of the HMTase reaction. In Su(var)3-9ptn a significantly enhanced enzymatic activity results in H3K9 hypermethylation, enhanced gene silencing and extensive chromatin compaction. Mutations in factors controlling active histone modification marks revealed the dynamic balance between euchromatin and heterochromatin. Further analysis and definition of Su(var) and E(var) genes in Drosophila will increase our understanding of the molecular hierarchy of processes controlling higher-order structures in chromatin.

Amino Acid Sequence↗

A modification of the kinetic equations used for describing the thermoluminescence phenomenon.

In the present work we discussed the validity of the traditional first-, second- and general-order kinetic equations used to describe the thermoluminescence (TL) phenomenon. These equations were written in their present forms to explain the TL glow peaks at constant value of the heating rate. However, a widespread mistake was found when one uses these equations to explain the TL at different heating rates. This mistake is a result of unreal definition of the rate of change of trapped carriers as a function of temperature. A modification of the above-mentioned equations has been considered during this work to define correctly the TL phenomenon. As a result of this modification some characteristics of the TL glow peaks, namely, the TL intensity and the total integral will be changed. Following to the present work, an emendation of Chen-Winer method used to determine the activation energy of TL glow peak was considered during this work. Also, a modification of the equation used to determine the relative value of initial concentration of the trapped carriers was considered during this work.

Journal Article↗

[Effect of chemical modification of lipase on the regulation of its lipolytic activity in reversed micelles].

Hydrophilized and hydrophobized forms of the lipase from Mucor miehei were obtained by its chemical modification with cellobiose and N-hydroxysuccinimidyl palmitate with a modification degree of 4 in both cases. A comparative analysis of the regulation of the catalytic activities of the native and modified lipases was carried out in the system of reversed micelles of OT aerosol (AOT) in isooctane. The level of catalytic activity of all the lipase preparations in the micellar medium was found to be higher than that in aqueous solution. The chemical modification of lipase did not result in a change in the regulation of the oligomeric composition of the enzyme controlled by the degree of micelle hydration omega0 (micelle size). The kcat dependences on omega0 for each lipase preparation exhibit two maxima, corresponding to the functioning of lipase monomers and tetramers. The changes in the hydrophilic-lipophilic balance of the lipase surface significantly affect the character of the regulation of enzyme activity due to changes in the surfactant concentration (the number of micelles). The lipase hydrophobization results in a decrease in the enzyme activation effect with an increase in the AOT concentration in comparison with the native lipase. The lipase hydrophilization dramatically decreases the activity of lipase tetramer when the AOT concentration is increased. The catalytic activity of the monomer of hydrophilized lipase is practically independent of the AOT concentration. Kinetic data indicate a mixed type of activation of both oligomeric forms of the native and the hydrophobized lipase by AOT molecules and the noncompetitive type of the activation and AOT inhibition of the monomer and the tetramer of the hydrophilized lipase, respectively. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2005, vol. 31, no. 6; see also http://www.maik.ru.

Catalysis↗