Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0267964 (PAA)
 2,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A hapten-specific unresponsive state was induced in vitro by the incubation of normal murine spleen cells with highly conjugated dinitrophenylated bovine gamma-globulin (DNP-BGG) or a dinitrophenylated copolymer of D-glutamic acid and D-lysine (DNP-D-GL) for 24 hr. After this incubation period spleen cells were washed and cultured for 4 days with the thymic-independent antigen dinitrophenylated polyacrylamide beads (DNP-PAA) or the thymic-dependent antigen trinitrophenylated burro the erythrocytes (TNP-BRBC). Preincubation with either DNP-BGG or DNP-D-GL led to a specific depression of the in vitro anti-hapten plaque-forming cell response. The degree of depression was dependent upon the concentration of the tolerogen and the duration of preincubation. The response to DNP-PAA or TNP-PAA beads was depressed to a greater degree than was the response to TNP-BRBC. The cellular basis of the immunologic unresponsiveness induced by DNP-BGG was attributable to an inhibition of B cell function whereas the unresponsive state induced with DNP-D-GL was due to both a specific inhibition of B cell function and the activation of antigen-specific suppressor T cells.
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PMID:Cellular basis for a hapten-specific state of tolerance induced in vitro. 8 Dec 28

The plasma amino acid response to single test meals was studied in preschool children, aged 9 months--5 years. The amount of protein given in each test meal was 1 g per kg body weight, which represented one-third of the daily intake of the children who were recovering from protein-energy malnutrition. The test meals given was gruels made from wheat mixed with a supplementary weaning food (Faffa or Superamin) or fish protein concentrate (FPC). The plasma amino acid responses were evaluated both as PAA ratios (a modification of the Longenecker and Hause method), and as deltaMR% (percentage change in the postprandial essential amino acid molar ratios according to Graham and Placko). Both evaluation models indicated that lysine, threonine and methionine were the limiting amino acids in the Faffa/wheat diet, and that lysine and threonine were limiting in the Superamin/wheat diet. All essential amino acids seemed to be supplied in adequate amounts in the FPC/wheat diet. These results were in close agreement with the amino acid score of the diets (based on chemical analysis).
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PMID:Plasma amino acid response to single test meals in humans. V. Ethiopian preschool children given lowcost protein supplements. 42 53

The plasma amino acid response to single test meals in young adults was used to determine the amount of physiologically available lysine in heat-treated milk samples. The plasma amino acid responses were evaluated as PAA ratios according to a modified calculation procedure based on the method proposed by Longenecker and Hause. The amount of available lysine was determined by two separate series of single-meal tests. In the first, a relationship was established between the plasma amino acid response (PAA ratio) and the dietary level of lysine (given as synthetic amino acid mixtures). This relationship could be described by linear regression (r = 0.90). This regression line was then used to quantitatively evaluate the lysine PAA ratios obtained from single test meals with heat-treated milk samples. The heat-treatment of the milk samples caused a marked reduction of the amount of physiologically available lysine. The quantitative estimates obtained by the present plasma amino acid technique were in good agreement with determinations of available lysine in the same milk samples based on rat bioassay and chemical analysis.
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PMID:Plasma amino acid response to single test meals in humans. VI. Determination of available lysine. 58 11

The postprandial plasma amino acid response to test meals containing different amino acid mixtures was analysed in six young adults. The amount of amino acids given in each test meal was equivalent with 3.5 g of nitrogen. Each test meal also contained a large amount of carbohydrate (mainly as wheat starch). Five different amino acid mixtures were used, and the effects on the plasma amino acid response of different dietary levels of lysine, isoleucine and methionine were studied in detail. The plasma amino acid responses were evaluated both by a modified Longenecker and Hause procedure (PAA ratios) and by the procedure proposed by Graham and Placko (percentage changes in the postprandial essential amino acid molar ratios). The plasma amino acid response of lysine was found to be less sensitive to reductions in the dietary supply than the isoleucine and methionine responses evaluated by these procedures. The influence of altered levels of dietary supply on the postprandial plasma concentrations of isoleucine and methionine seemed to be specifically great at the intake levels where these essential amino acids become limiting for protein utilization according to the amino acid score of the test mixtures. The nutritional significance of the postprandial pattern and level of essential amino acids is discussed on basis of the present results. Experimental conditions and evaluation models are examined with regard to the use of single-meal plasma amino acid responses to assess the protein quality of human diets.
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PMID:Plasma amino acid response to single test meals in humans. II. Healthy young adults given synthetic amino acid mixtures. 73 42

By means of radioligand analysis, murine peritoneal macrophages were shown to express several hundreds cell surface high-affinity GMDP-binding sites with a binding constant 350 pM. Photoaffinity labeling followed by SDS-PAGE enabled us to identify inside these cells 32-34 and 38 kDa proteins, specifically binding GMDP. Proteins 32-34 kDa were also detected by Western blotting analysis using biotinylated conjugate of polyacrylamide with immobilized GMDP-Lys [(GMDP-Lys)-PAA-(Bi)] in cell lysate of murine peritoneal macrophages.
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PMID:[Polypeptides from murine peritoneal macrophages recognizing glycosaminylmuramoyl dipeptide]. 778 17

Gene transfer vectors formed between the cationic polyamino acid, poly-(L)-omithine (PLO) and plasmid DNA (pDNA) have demonstrated superior transfection efficiency (up to x 10-fold) compared to equivalent polylysine-based systems in-vitro. The mechanism(s) underlying this observation remains to be elucidated. We previously reported no significant difference in colloidal particle size or zeta potential of polycation/pDNA complexes formed with poly-(L)-lysine (PLL), poly-(D)-lysine (PDL) or PLO. Here we report spectrofluorometric analysis indicating that PLO condenses pDNA at lower charge (+/-) ratios than PLL or PDL (cf. 0.8:1, 1.2:1 and 1.5:1). Moreover, PLO/pDNA complexes proved more stable to disruption by the polyanions, poly-(L)-aspartic acid (PAA) and heparin. There were no qualitative differences in the ability of the polycations to protect complexed pDNA from enzymatic degradation both in the presence and in the absence of polyanions. The superior transfection efficiency of PLO/pDNA complexes did not appear to be mediated by an increased cellular delivery of pDNA. The data suggests a greater affinity of PLO for pDNA as an important parameter for the observed superior in-vitro transfection efficiency.
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PMID:Polylysine and polyornithine gene transfer complexes: a study of complex stability and cellular uptake as a basis for their differential in-vitro transfection efficiency. 1199 81

The blocking potency of P- and L-selectin was studied for certain small molecule mannosides and their polyacrylamide (PAA, 30 kDa) conjugates in comparison to SiaLe(x) and fucoidan. Two experimental systems were used: (1) solid phase static assay based on recombinant selectins, and (2) P-selectin dependent rat peritoneal inflammation. betaMan-SC6H4NO2- p was four times more potent P-selectin inhibitor as compared to SiaLe(x). Docking of this molecule onto the P-selectin carbohydrate-binding site demonstrated that a nitro group enabled an electrostatic interaction with residue Lys 84, while the phenyl ring and the CH2 at C-6 contacted the CH2 groups of the same Lys residue. In vivo, betaMan-SC6H4NO2- p blocked experimental inflammation better than SiaLe(x), but significantly lower than fucoidan. In vitro Man-polyacrylic acid conjugates appeared to be very potent inhibitors comparable to fucoidan, uncharged Man-PAA proved rather active, comparable to SiaLe(x)-PAA both in vitro, and in vivo, whereas mannan did not display any P-selectin blocking effect.
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PMID:Uncharged P-selectin blockers. 1500 41

On exposure to an acidic pH, linear poly(amidoamine)s (PAAs) cause membrane perturbation and consequently have potential as endosomolytic polymers for the intracellular delivery of genes and toxins. Previous studies used PAAs in the hydrochloride form only. The aim of this study was to investigate systematically the effect of the PAA counterion on pH-dependent membrane activity, general cytotoxicity, and PAA solution properties to help guide optimization of PAA structure for further development of PAA-protein conjugates. PAAs (ISA 1, 4, 22, and 23; M(w) 10000-50000 g/mol) were synthesized to provide a library of PAAs having different counterions including the acetate, citrate, hydrochloride, lactate, phosphate, and sulfate salts. pH-Dependent membrane activity was assessed using a rat red blood cell haemolysis assay (conducted at a starting pH of 7.4, 6.5, or 5.5; 1 mg/mL; 1 h), and general cytotoxicity was investigated using a murine melanoma cell line (B16F10) and a human bladder endothelial-like cell line (ECV-304). Whereas poly(ethyleneimine) was haemolytic at the starting pH of 7.4 at 1 h [ approximately 50% haemoglobin (Hb) release], none of the PAA salts were haemolytic at a starting pH of 7.4 or 6.5. Although PAA acetate, citrate, and lactate were also non-haemolytic at the starting pH of 5.5, the sulfate and hydrochloride forms caused significant haemolysis (up to 80% Hb release) and ISA 22 and 23 phosphate were also markedly haemolytic ( approximately 70% Hb release). These counterion-specific differences were also clearly visible using scanning electron microscopy, which was used to visualize the red blood cell morphology. All PAAs were relatively nontoxic (IC(50) >or= 300-5000 microg/mL) compared to poly-l-lysine (IC(50) = 2-10 microg/mL), the PAA hydrochloride salts produced the greatest cytotoxicity, and the B16F10 cells were more sensitive than the ECV-304 cells. Small-angle neutron scattering suggested that ISA 23 hydrochloride had a larger hydrodynamic radius (5.1 +/- 0.2 nm) than the citrate salt (3.1 +/- 0.2 nm). These results provide indirect evidence for the salt- and pH-dependent changes in the conformation of the polymer coil. This study clearly demonstrates the importance of optimization of the counterion form when developing endosomolytic polymers designed to mediate pH-dependent membrane permeabilization.
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PMID:Poly(amidoamine) salt form: effect on pH-dependent membrane activity and polymer conformation in solution. 1513 5

The amidase activity of bovine pancreas trypsin in water-soluble complexes with poly(ethylene glycol)-block-poly(alpha,beta-aspartic acid) (PEG-PAA) was evaluated by a colorimetric assay using L-lysine p-nitroanilide as a substrate. The enzymatic reaction of trypsin was accelerated through the complexation with PEG-PAA. By determining the kinetic parameters of the enzymatic reaction of trypsin, it was confirmed that the catalytic rate constant of the complexed trypsin was 15 times higher than that of the native trypsin. From the evaluation of pH dependence of initial reaction rate, it was indicated that this acceleration was induced by a stabilization of the imidazolium ion of the His residue in the catalytic site, the Asp-His-Ser triad, of trypsin due to the Asp units of PEG-PAA. The hydrogen bonded Asp-His pairs are critical constituents in several key enzymatic reactions including serine protease and apurinic endonucleases, and it was expected that the acceleration of the catalytic reaction might occur for other enzymes by the formation of water-soluble complexes with PEG-PAA.
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PMID:Acceleration of enzymatic reaction of trypsin through the formation of water-soluble complexes with poly(ethylene glycol)-block-poly(alpha,beta-aspartic acid). 1576 22

Controlled drug delivery and gene transfection involve contact of artificial polyelectrolytic systems that can interact dramatically with biopolymers and cells when they are introduced in blood. Given the complexity of body aqueous media in terms of physical chemistry, a model approach was selected in attempt to understand the behavior of artificial polyelectrolytes introduced in body fluids. Selection in terms of molecular weight was highlighted in a previous paper. In the present study the formation and the stability of fractions obtained when a polycation is added to a polyanion according to a titrating process mimicking injection into blood was considered for different polycation/polyanion couples. Poly(amino serinate) and poly(L-lysine) were used as polybases, and poly(acrylic acid), poly(L-lysine citramide) and poly(L-lysine citramide imide) as polyacids. Four fractions corresponding to different positive/negative charge ratios were formed for each couple. At low polyion concentration (13 mg/L) and given salt concentration, the stability of the complex fractions depended on molecular weight and charge density of the polyions. The NaCl concentration required to destabilize the different interpolyelectrolyte complexes was found to decrease from the first fraction to the fourth one. Upon decreasing the salt concentration, macroscopic flocculation occurred in the case of PLL/PAA complex fractions only. For the other couples, dynamic light scattering showed that several hundreds nanometer sized particles were formed that were stable in a broad range of NaCl concentration, including the physiological 0.15 ionic strength. At higher polyion concentrations, stable solid precipitate was formed regardless of the system. The absence of flocculation in the case of highly diluted poly(L-lysine citramide) and poly(L-lysine citramide imide) polyanions in salted media is assigned to the presence of non-ionic hydroxyl and amide polar groups along the complexed chains. Data show that introducing non-ionic functions along the polyelectrolyte chains is a good means to keep interpolyelectrolyte complexes dispersed in salted media, a conclusion of interest in the field of condensation of genes by polycations.
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PMID:Polyelectrolyte complex formation and stability when mixing polyanions and polycations in salted media: a model study related to the case of body fluids. 1591 Dec 24


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