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 919 records · Page 51Linked to original sources
PubMed1985

Coronary heart disease and risk factor modification. Is there a threshold?

Modification of coronary heart disease risk factors may play an important role in the control and alteration of the atherosclerotic process. The amount of modification necessary to obtain beneficial results is a controversial issue. Review of epidemiologic studies and recent arteriographic investigations allows for the approach to the issue of threshold levels of modification that may be required prior to obtaining some benefit. Serum lipoproteins appear to play a central role in the atherosclerotic risk factor relationship. On the basis of current evidence, clinical aims are suggested for coronary heart disease risk factor modification in order to assist in obtaining optimal health goals.

Adult↗
PubMed1993

Susceptibility of small, dense, low-density lipoproteins to oxidative modification in subjects with the atherogenic lipoprotein phenotype, pattern B.

PURPOSE: To test whether low-density lipoprotein (LDL) from subjects with an atherogenic lipoprotein phenotype characterized by small, dense LDL (pattern B) demonstrates greater susceptibility to oxidative modification than LDL from subjects exhibiting primarily larger, more buoyant LDL particles (pattern A). PATIENTS AND METHODS: Measures of susceptibility to oxidative modification were compared in six density subfractions of LDL isolated from pattern A and pattern B subjects. Seven male and three female pattern A subjects and five male and two female pattern B subjects, classified on the basis of peak LDL particle size, were studied. Plasma lipid and lipoprotein levels, apolipoprotein B, mean LDL particle diameter, lag phase, and rate of oxidation after initiation of oxidation by copper sulfate were measured. RESULTS: The lag time, a measure of resistance to oxidative modification, was inversely related (p < 0.001) to LDL density in both groups of subjects, without an independent effect of phenotype. The fraction that had the major LDL peak had a shorter lag time (p < 0.05) in pattern B than in pattern A. Pattern B subjects also demonstrated an increased rate of oxidation (p < 0.005) in fraction 1, which includes remnants of triglyceride-rich lipoproteins. CONCLUSIONS: The increased atherogenic risk associated with the pattern B phenotype may result in part from increased concentrations of lipoprotein subpopulations that are relatively susceptible to oxidative modification.

Adult↗
PubMed1985

Chemical modification of S-adenosylhomocysteinase by a water-soluble carbodiimide.

S-Adenosylhomocysteinase (EC 3.3.1.1) from rat liver is inactivated by 1-cyclohexyl-3-(2-morpholinoethyl)carbodiimide metho-p-toluenesulfonate (CMC) in a pseudo-first-order fashion. The rate of inactivation is linearly related to the concentration of the reagent, and a second-order rate constant of 4.94 +/- 0.27 M-1 min-1 is obtained at pH 5.5 and 25 degrees C. The inactivation does not involve change in the quaternary structure of the enzyme nor modification or release of the enzyme-bound NAD. Lack of modification at tyrosine, serine, cysteine, histidine, and lysine residues and the fact that the inactivation is favored at low pH suggest that the inactivation is caused by the modification of a carboxyl group. Statistical analysis of the relationship between the residual enzyme activity and the extent of modification, and comparison of the number of residues modified in the presence and absence of the substrate adenosine show that, among four reactive residues per enzyme subunit, only one residue which reacts more rapidly with the reagent than the rest is critical for activity. The CMC-modified enzyme binds adenosine and S-adenosylhomocysteine and is able to oxidize the 3' hydroxyl of these substrates, but apparently fails to catalyze the abstraction of the 4' proton of adenosine.

Adenosylhomocysteinase↗
PubMed1988

Ethanol-induced modifications to membrane lipid structure: effect on phospholipase A2-membrane interactions.

Chronic ethanol intoxication leads to the development of a resistance to lipid disordering by ethanol, a phenomenon known as "membrane tolerance". In the absence of the added ethanol, the lipid order, as measured by ESR and fluorescence techniques, does not necessarily change as a result of chronic ethanol ingestion (as in liver microsomes, for example). This suggests that the spectroscopic techniques detect tolerance somewhat indirectly, in that the modification responsible may reside in a region distinct from that being probed and also raises the question of whether membrane tolerance is necessarily associated with an alteration in the membrane lipid structure. Here we show that liver microsomes from rats treated chronically with ethanol are rendered relatively resistant to the hydrolytic action of exogenous phospholipase A2, compared to preparations from control animals. This resistance persists in reconstituted lipid vesicles prepared from extracted phospholipids. Since the same substrate (1-palmitoyl-2-N-(4-nitrobenzo-2-oxa-1,3-diazole)amino caproylphosphatidylcholine) was used in both membranes from ethanol-treated animals and controls, the modification appears to reside in the structure and/or organization of the membrane. Further evidence that the lipid structure is modified by chronic ethanol treatment is provided by the observation that perturbance of the membrane structural integrity by increasing levels of oleic acid led to a progressive loss of the ethanol-induced relative resistance to hydrolysis by phospholipase A2. The results of this study support the idea that membrane tolerance involves a modification to lipid structure probably at the bilayer surface. The use of exogenous phospholipase A2 provides a new method for probing the structural modifications induced by chronic ethanol ingestion.

Animals↗
PubMed1989

Stopped-flow chemical modification with N-bromosuccinimide: a good probe for changes in the microenvironment of the Trp 62 residue of chicken egg white lysozyme.

The stopped-flow chemical modification with N-bromosuccinimide (NBS) of Trp 62 of hen (chicken) egg white lysozyme (EC 3.2.1.17) was found to depend greatly on pH: it was not observed at pH's above 7, but it was observed at pH's lower than 6. In addition, at pH's between 6 and 7 the NBS modification showed a delta epsilon pH profile similar to a "titration curve," giving a pK (congruent to 6.5) nearly equal to the pK (congruent to 6.2) of a catalytic residue, Glu 35. The stopped-flow chemical (NBS) modification of N-acetyl-L-tryptophan ethyl ester, a model compound of Trp 62, does not depend on pH at the pH's examined, approximately 3.5-8.5. These experimental results suggest that a change in the state of Trp 62 at Subsite C is induced by protonation-deprotonation of an ionizable residue, which could be Glu 35 (catalytic site), indicating that stopped-flow NBS modification is a good probe for detection of changes in the micorenvironment around the tryptophan residue(s) of enzymes.

Binding Sites↗
PubMed1990

Chemical modification of chalcone isomerase by diethyl pyrocarbonate: histidine residues are not essential for catalysis.

Chalcone isomerase form soybean is inactivated by treatment with diethyl pyrocarbonate (DEP). The competitive inhibitor 4',4-dihydroxychalcone provides kinetic protection against inactivation by DEP with a binding constant at the site of protection in agreement with its binding constant at the active site. Very high concentrations of the competitive inhibitors 4',4-dihydroxychalcone or morin hydrate offer a 10- to 40-fold maximal protection, suggesting a second slower mechanism for inactivation which cannot be prevented by blockage of the active site. Blockage of the only cysteine residue in chalcone isomerase with p-mercuribenzoate does not affect the rate constant for DEP-dependent inactivation and indicates that the modification of the cysteine residue is not responsible for the activity loss observed in the presence of DEP. Treatment of inactivated enzyme with hydroxylamine does not restore catalytic activity, indicating that the modification of histidine or tyrosine residues is not responsible for the activity loss. All five histidines of chalcone isomerase are modified by DEP at pH 5.7 and ionic strength 1.0 M. The rate constant for the modification of the histidine residues of chalcone isomerase is close to that for the reaction of N-acetyl histidine with DEP, indicating that the histidine residues are quite accessible to the modifying reagent. The rate of histidine modification is the same in native enzyme, in urea-denatured enzyme, and in the presence of a competitive inhibitor. In the presence of the competitive inhibitor morin hydrate, all of the histidine residues of chalcone isomerase can be modified without significant loss in catalytic activity. These results demonstrate that the histidine residues of chalcone isomerase are not essential for catalysis and therefore cannot function as nucleophilic catalysts as previously proposed.

Binding Sites↗
PubMed1981

Covalent modification of chloroplast photosystem II polypeptides by p-nitrothiophenol.

Illumination of the chlorophyll a/b light-harvesting complex in the presence of p-nitrothio[14C]phenol caused quenching of fluorescence emission at 685 nm (77 K) relative to 695 nm and covalent modification of light-harvesting complex polypeptides. Fluorescence quenching saturated with one p-nitrothiophenol bound per light-harvesting complex polypeptide (10-13 chlorophylls); 1/2 maximal quenching occurred with one p-nitrothiophenol bound per light-harvesting complex polypeptides (190-247 chlorophylls). This result provides direct evidence for excitation energy transfer between light-harvesting complex subunits which contain 4-6 polypeptides plus 40-78 chlorophylls per complex. Illumination of chloroplasts or Photosystem II (PS II) particles in the presence of p-nitrothio[14C]phenol caused inhibition of PS II activity and labeling of several polypeptides including those of 42-48 kilodaltons previously identified as PS II reaction center polypeptides. In chloroplasts, inhibition of oxygen evolution accelerated p-nitrothiophenol modification reactions; DCMU or donors to PS II decreased p-nitrothiophenol modification. These results are consistent with the hypothesis that accumulation of oxidizing equivalents on the donor side of PS II creates a 'reactive state' in which polypeptides of PS II are susceptible to p-nitrothiophenol modification.

Chlorophyll↗
PubMed1982

Modification of bovine heart mitochondrial transhydrogenase with tetranitromethane.

Modification of pyridine dinucleotide transhydrogenase with tetranitromethane resulted in inhibition of its activity. Development of a membrane potential in submitochondrial particles during the reduction of 3-acetylpyridine adenine dinucleotide (AcPyAD+) by NADPH decreased to nearly the same extent as the transhydrogenase rate on tetranitromethane treatment of the membrane. Kinetics of the inactivation of homogeneous transhydrogenase and the enzyme reconstituted into phosphatidylcholine liposomes indicate that a single essential residue was modified per active monomer. NADP+, NADPH and NADH gave substantial protection against tetranitromethane inactivation of both the nonenergy-linked and energy-linked transhydrogenase reactions of submitochondrial particles and the NADPH leads to AcPyAD+ reaction of reconstituted enzyme. NAD+ had no effect on inactivation. Tetranitromethane modification of reconstituted transhydrogenase resulted in a decrease in the rate of coupled H+ translocation that was comparable to the decrease in the rate of NADPH leads to AcPyAD+ transhydrogenation. It is concluded that tetranitromethane modification controls the H+ translocation process solely through its effect on catalytic activity, rather than through alteration of a separate H+-binding domain. Nitrotyrosine was not found in tetranitromethane-treated transhydrogenase. Both 5,5'-dithiobis(2-nitrobenzoate)-accessible and buried sulfhydryl groups were modified with tetranitromethane. NADH and NADPH prevented sulfhydryl reactivity toward tetranitromethane. These data indicate that the inhibition seen with tetranitromethane results from the modification of a cysteine residue.

Animals↗
PubMed1987

Inactivation of the mitochondrial ATPase inhibitor protein by chemical modification with diethylpyrocarbonate.

Modification of histidine residue(s) by diethylpyrocarbonate treatment of submitochondrial particles obtained by sonication results in inhibition of ATPase activity and stimulation of oligomycin-sensitive H+ conduction. The inhibition of the ATPase (EC 3.6.1.3) activity persisted in F1 isolated from diethylpyrocarbonate-treated submitochondrial particles, which exhibited the absorbance spectrum of modified histidine. Thus the inhibition of the ATPase activity results from histidine modification in F1 subunits. Removal of the natural inhibitor protein from submitochondrial particles resulted in stimulation of proton conduction. After removal of F1 inhibitor protein from the particles the stimulatory effect exerted by diethylpyrocarbonate treatment on proton conduction was lost. Reconstitution experiments showed that purified F1 inhibitor protein lost, after histidine modification, its capacity to inhibit the ATPase activity and proton conduction. These observations show that the stimulation of proton conduction by the ATPase complex effected by diethylpyrocarbonate treatment results from histidine modification in F1 inhibitor protein.

Animals↗
PubMed1979

Chemical modification of the epsilon-amino groups of lysine residues in horseradish peroxidase and its effect on the catalytic properties and thermostability of the enzyme.

Chemical modification of horseradish peroxidase (donor:hydrogen-peroxide oxidoreductase, EC 1.11.1.7) (isoenzyme C) by anhydrides of mono- and dicarboxylic acids and picryl sulfonic acid has been performed. The effect of the modification on the catalytic activity, absorption and circular dichroism spectra of peroxidase has been studied. Rate constants of irreversible thermoinactivation (kin) for the native and modified peroxidase at 56--80 degrees C have been measured. The effective values of the thermodynamic activation parameters of thermoinactivation, delta H not equal to and delta S not equal to, have been also determined. A relationship between the number of modified epsilon-amino groups of lysine residues and the nature of the modifier on the one hand, and the conformation and thermostability of the enzyme on the other, is discussed. It has been shown that it is the degree of modification, rather than the nature of the modifier, that produces the major effect on the macromolecular conformation and the thermostability of the enzyme after modification. The conclusion is drawn that the thermostability of the modified enzyme increases due to the decrease of the conformational mobility in the protein moiety around the heme.

Chemical Phenomena↗
PubMed1981

Inactivation of crystalline tobacco ribulosebisphosphate carboxylase by modification of arginine residues with 2,3-butanedione and phenylglyoxal.

Crystalline tobacco ribulosebisphosphate carboxylase (3-phospho-D-glycerate carboxylase (dimerizing), EC 4.1.1.39) is rapidly and completely inactivated by 2,3-butanedione in borate buffer or phenylglyoxal, reagents which are highly specific for the modification of arginine residues. Inactivation by phenylglyoxal is enhanced in Bicine buffer and partially reversible, whereas inactivation by butanedione is markedly enhanced in borate buffer, irreversible in the presence of borate and partially reversed upon complete removal of borate and excess reagent. When the modification reaction is performed in the presence of various ligands, only the substrate ribulosebisphosphate and the diphosphorylated competitive inhibitor sedoheptulosebisphosphate protect against inactivation. Loss of carboxylase activity is directly proportional to incorporation of [14C]phenylglyoxal until about 15% of the initial activity remains. Extrapolation to zero activity suggests that inactivation by [14C]phenylglyoxal correlates with the modification of three arginine residues per 69 000 dalton protomer. Complete protection by ribulosebisphosphate or sedoheptulosebisphosphate correlates with the shielding of 1-2 (1.27 +/- 0.25) essential arginyl groups per protomer, which are located within the 55 000 dalton catalytic subunits of the protein. Similarly, amino acid analyses of acid hydrolysates of the butanedione- or phenyl-glyoxal-inactivated and substrate-protected enzymes suggest that complete protection by ribulosebisphosphate correlated with the shielding of 1.9-2.4 arginine residues per protomer. However, modification of the control and substrate-protected enzymes are these arginine-selective alpha-dicarbonyls does not alter modulation by anionic effectors.

Aldehydes↗
PubMed1988

Role of superoxide in endothelial-cell modification of low-density lipoproteins.

Cultured endothelial cells and arterial smooth muscle cells have been shown to modify LDL in a way that leads to rapid uptake by macrophages. Previous studies have demonstrated that this modification involves free radical peroxidation of LDL, and that the role of the cells was to accelerate oxidation under conditions where it otherwise would occur slowly. The objective of the present study was to determine whether the modification was mediated by oxygen-derived free radicals, and whether the ability of a given cell type of line to modify LDL was related to its secretion rate of O2- or H2O2. The results showed that modification required the presence of oxygen, and could be specifically inhibited by superoxide dismutase but not by catalase or by mannitol, a hydroxyl radical scavenger. Rabbit aortic endothelial cells, rabbit arterial smooth muscle cells, monkey arterial smooth muscle cells and human skin fibroblasts were all found to modify LDL, and all of these cell types generated more O2- (superoxide dismutase-inhibitable cytochrome c reduction) than a line of bovine aortic endothelial cells that did not modify LDL. The content of superoxide dismutase and catalase was higher in bovine aortic endothelial cells than in the cell lines that modified LDL, but glutathione peroxidase levels were not different. It was concluded that cells that were capable of modifying LDL produced superoxide or a substance that could be converted to superoxide in the medium, and that superoxide was an important, though possibly indirect, mediator of the modification of LDL by cells.

Animals↗
PubMed1992

Direct modification of low density lipoprotein by the spin trap 3,5-dibromo-4-nitrosobenzenesulfonic acid.

We have previously reported that the spin trap alpha-phenyl-tert-butyl nitrone (PBN) inhibited the oxidative modification of low density lipoprotein (LDL) (Kalyanaraman, B., Antholine, W.E. and Parthasarathy, S. (1990) Biochim. Biophys. Acta 1035, 286-292). In the present study, we report that 3,5-dibromo-4-nitrosobenzenesulfonic acid (DBNBS), a water-soluble spin trap, also inhibited the oxidation of LDL as measured by the formation of thiobarbituric acid reactive substances (TBARS). However, when compared with LDL incubated without DBNBS, the DBNBS-incubated LDL showed increased negative charge on agarose gel electrophoresis and was avidly degraded by mouse peritoneal macrophages. Despite the suggestion of biological modification, there was no decrease in lysine-amino groups in DBNBS-incubated LDL. Furthermore, reductively methylated LDL in which more than 85% of the amino group of lysines was blocked, was also modified by DBNBS. A sulfonic acid analog of PBN failed to modify LDL in a similar manner, suggesting that the presence of sulfonic acid alone does not ensure modification. When LDL was incubated with DBNBS, radical adducts associated with both lipid and protein were detected by electron paramagnetic resonance (EPR) technique. It is suggested that DBNBS may bind to the apoprotein B100 and lipids of LDL by a lysine-independent mechanism resulting in increased recognition and degradation by macrophages. The present work offers a novel approach for rapid modification of LDL.

Benzenesulfonates↗
PubMed1976

Steroid-protein interactions. XXXIV. Chemical modification of alpha1-acid glycoprotein for characterization of the progesterone binding site.

The nature of the steroid binding site in alpha1-acid glycoprotein (orosomucoid) was investigated by chemical modification of individual amino acids and subsequent examination of the binding affinity for progesterone. Equilibrium dialyses were performed under conditions that excluded contact with human skin. Reaction of the lysyl residues with trinitrobenzenesulfonic acid or arylisocyanates resulted in a reduction of active sites. In an alternate approach, one lysyl residue of alpha1-acid glycoprotein was protected from modification by trinitrobenzenesulfonic acid when progesterone was present to form the complex with alpha1-acid glycoprotein. We conclude that a lysyl residue is located in the binding site. Reaction of tetranitromethane with the tyrosine groups in alpha1-acid glycoprotein also reduced the number of active binding sites for progesterone. Again, a partial protection of this modification was seen in the presence of progesterone and other delta4-3-ketosteroids. The progesterone binding activity observed in the tyrosine-modified alpha1-acid glycoprotein by equilibrium dialysis and by fluorescence quenching titration can be interpreted best by the presence of one tyrosyl residue in the binding site, and involvement of a second tyrosine nearby. Modification of tryptophan in alpha1-acid glycoprotein by mild acid hydrolysis, N-bromosuccinimide, hydroxynitrobenzylbromide, and formic acid resulted in a decreased steroid binding; the formylation reaction was fully reversible. The approximate distance between progesterone and the tryptophan involved in the binding was calculated to be between 9.1 A and 14.1 A. When alpah1-acid glycoprotein was cleaved by the cyanogen bromide procedure according to Ikenaka et al. (1972, Biochemistry 11, 3817-3829), both the amino and the carboxyl fragment had a weak progesterone binding affinity which could be measured in 4 M NaCl. This result thus failed to specify the location of the steroid binding site in alpha1-acid glycoprotein. However, the closeness of tryptophan, lysine and tyrosine in the primary and presumably the tertiary structure of alpha1-acid glycoprotein is in agreement with the properties of the binding site suggested by our studies.

Benzenesulfonates↗
PubMed1978

Functional consequences of tryptophan modification in human fibrinogen.

When human fibrinogen was modified with H2O2, inter- and intra-molecular cross-links of fibrinogen were formed, accompanied with oxidation of tryptophan, methionine and tyrosine residues. These cross-links may be closely associated with oxidation of tryptophan residues. The polymerization activity of fibrinogen with thrombin was decreased markedly by this modification. Modification of tryptophan residues in fibrinogen was also performed with 2-hydroxy-5-nitrobenzyl bromide. Modification of two out of a total 78 tryptophan residues in the molecule with the reagent led to the intensification (1.7 times) of the polymerization activity with thrombin and further modification of the next two residues led to complete loss of the polymerization activity. The first two tryptophan residues to be modified are in Fragment D, and the next two occur in Fragment E.

2-Hydroxy-5-nitrobenzyl Bromide↗
PubMed1981

Effects of chemical modification on the conformation and biological activity of peanut agglutinin.

The effect of chemical modifications on the biological properties of peanut agglutinin was investigated. The free amino groups were modified with succinic anhydride and 1-isothiocyanato-4-benzenesulfonic acid. Though the extent of modification was 95 and 85%, respectively, these derivatives did not lose their sugar binding capacity. The agglutinating activity with neuraminidase-treated human erythrocytes and various tumor cells was reduced. The mitogenic activity tested with neuraminidase-treated human lymphocytes was also diminished The tyrosine residues were modified with tetranitromethane and further with 4-aminophenyl-alpha-D-glucopyranoside and the negatively charged 2-(4-amino-benzyl)-alpha-D-neuraminic acid. The extent of modification was 30, 28 and 6%, respectively. The agglutinating and mitogenic activities were in this case not severely changed. The influence of all these modifications on the conformation was investigated by means of CD studies in the far and near ultraviolet regions.

Agglutination↗
PubMed1981

Stability of lactate dehydrogenases. I. Chemical modification of lysines.

The lysine residues of lactate dehydrogenase (L-lactate: NAD+ oxidoreductase, EC 1.1.1.27) can be amidinated by methyl-4-hydroxy-3-nitrobenzimidate to introduce nitrophenolate anions. This modification results in lowered thermal stability, as does acetylation. The conversion of these groups into uncharged aminophenol groups without further modification of the enzyme itself stabilizes the enzymes from pig heart and muscle and from chicken muscle, as does acetamidination, but the unusually stable enzyme from chicken heart reverts only to the stability of the native form. The results allow for the following conclusions. Destabilization is brought about at many points at the surface of lactate dehydrogenases by neutralization of positive charges. Stabilization, in contrast, is concluded to be due to modification of one lysine at position 241 of the sequence. This lysine must have been changed to arginine during the evolution of heart-type lactate dehydrogenases in going from lower to higher reptiles. This exchange has been conserved in the enzymes from the hearts of birds and therefore the enzyme from chicken heart is very stable and cannot further be stabilized by modification of lysines. From X-ray structure analysis, the stabilization by exchange of Arg for Lys at position 241 or by amidination is explained by the formation of additional ion pairs with aspartic acid57 of the Q-related subunits.

Animals↗
PubMed1996

Biblical behavior modification.

Although we may have formalized and systematized the field of behavior modification in the last few decades, people around the world have been using behavioral change strategies throughout history. Premack's (1965) theory of reinforcement is often called "Grandma's rule" because grandmothers have long been using it (e.g. You must finish your vegetables before you may go out and play). Franks (1969, p. 4), in one of the first behavioral texts, gave historical examples from China, Turkey, France, and Italy. Knapp and Shodahl (1974) showed how Benjamin Franklin used behavior modification. And de Silva (1984, 1985) gave examples of behavior modification by the Buddha and other early Buddhists. Conspicuously absent from our literature are examples from the Judeo-Christian tradition. In this paper, we provide a number of behavior modification examples from the Bible (New International Version). Footnotes provide references for many more examples. In the discussion, we explore implications for education and therapy. Examples are grouped by the following categories: operant conditioning, respondent conditioning, modeling, and cognitive interventions. However, the Biblical examples, like contemporary case studies, do not always fall neatly into discrete categories. They often are a combination, particularly operant and respondent conditioning interweaving.

Behavior Therapy↗