Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P00790 (PGA)
 2,475 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Between April 1986 and July 1990 fractures of the olecranon in 41 adult patients were treated by fixation with absorbable rods (20 patients) and screws (21 patients) of self-reinforced polyglycolide (SR-PGA), 3.2 mm in diameter and 20-70 mm in length. Patients were followed up for a mean time of 2 years 7 months (range 1 year to 4 years 6 months). After reduction of the fracture, channels were drilled from the proximal fragment through the cortex of the distal fragment and the fractures were fixed with absorbable rods or screws. By one year from follow-up maintenance of an anatomical reduction of the fracture was seen in 34 patients. Failure of fixation requiring a second operation occurred in 2 cases. In all cases functional recovery was at least satisfactory. Sinus formation as a sign of transient tissue reaction was observed in 3 cases, but did not influence the healing of the fractures or the functional recovery. The results in patients treated with rods or screws was similar. Absorbable screws combined with small rods and absorbable sutures allow treatment of +ore severe fractures of the olecranon than do rods alone.
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PMID:[Absorbable rods and screws: a new method of fixation for fractures of the olecranon]. 142 37

The effect of reduced and oxidized folates on the development of methotrexate (MTX) resistance has been examined in human leukemia cell line K562 (K562/S). K562/S cells were made resistant to MTX by soft-agar cloning either in RPMI-1640 medium (K562/MTX-PGA) or in folic-acid-free RPMI-1640 medium containing 10 nM leucovorin (K562/MTX-LV). The optimal concentrations of leucovorin for the growth of K562/S, K562/MTX-PGA and K562/MTX-LV cells were 1 nM, 5 nM and 10 nM respectively. K562/MTX-PGA cells were 24-fold resistant to MTX as noted by impaired MTX transport. In contrast, K562/MTX-LV cells were 26-fold resistant to MTX as noted by gene amplification of dihydrofolate reductase. Furthermore cross-resistance to cytosine arabinoside was only demonstrated in K562/MTX-PGA, while the K562/MTX-LV cells showed no significant cross-resistance to cytosine arabinoside. These results suggest that the type and level of folates used during the development of MTX resistance may play a role in the mechanism for MTX resistance. Leukemia cells that are grown in leucovorin might serve as a model for acquired MTX resistance in vivo.
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PMID:The role of folates in the development of methotrexate resistance in human leukemia cell line K562. 142 25

71 patients with displaced ankle fracture were treated by using absorbable screws in the fixation of fractures. The follow-up time was 17 (13 to 33) months in average. The fixation devices were SR-PLLA (self-reinforced poly-L-lactide) and SR-PGA (self-reinforced polyglycolide) screws. 38 of the ankle fractures were immobilized with plaster cast and 33 ankle joints were mobilized immediately with a brace. An exact radiological result was achieved in 66 cases, insignificant displacement was observed in four cases and the result was poor in one patient. The result was classified as excellent in 62 patients, as good in eight patients and as poor in one patient. The patients treated postoperatively without plaster healed in a somewhat shorter time, but at one year check-up the differences in the clinical results were almost eliminated. Selected ankle fractures fixed with absorbable screws can be treated postoperatively with early mobilization without plaster.
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PMID:[Immobilization and early mobilization of malleolar fractures after osteosynthesis with resorbable bone screws]. 144 Oct 1

Exchange-inert beta, gamma-bidentate Cr(H2O)x(NH3)y ATP complexes inactivate yeast phosphoglycerate kinase (PGK) by forming a coordination complex at the enzyme active site. The observed inactivation rates ranged from 0.019 min-1 to 0.118 min-1 for Cr(NH3)4ATP and Cr(H2O)4ATP, respectively. Incorporation of one mol of Cr-ATP to the enzyme was sufficient for complete inactivation of the enzyme. The presence of Mg-ATP protected the enzyme against inactivation by Cr-ATP. The other substrate 3-phosphoglycerate (3-PGA), when present, reduced the observed inactivation rates. The reduction of the k(obs) by 3-PGA was proportional to the number of NH3 ligands present in the coordination sphere of Cr3+ in the Cr-ATP complex, suggesting that in the ternary enzyme-Cr-ATP-3-PGA complex 3-PGA may be coordinated to the metal ion. When the effector sulfate ion was present, the presence of 3-PGA did not cause any further effects on the observed inactivation rates. This suggests that bound substrates are in a different arrangement at the active site when sulfate is present and therefore 3-PGA may not need to displace a ligand from Cr3+. Additionally, PGK exhibited a stereoselectivity for the binding of Cr(H2O)4ATP. delta diastereomer of Cr(H2O)4ATP yielded an order of magnitude smaller Ki value compared to the value observed with the lambda isomer. The recovery of enzyme activity was observed over a period of a few hours upon removal of excess Cr-ATP. The presence of substrates and/or effector ion sulfate did not alter the observed reactivation rate. There was no difference in the reactivation rates of the enzyme which was inactivated with Cr(H2O)4ATP or Cr(NH3)4ATP with and without 3-PGA. Increasing the ligand exchange rates of Cr3+ of Cr-ATP by increasing the pH value of the recovery medium from 5.9 to 6.8 increased the rate of recovery by a factor of 8. The pH dependence of the reactivation indicated that one hydroxyl group is involved in the recovery of the enzyme activity in enzyme CrATP and enzyme.CrATP.3-PGA complexes.
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PMID:Inactivation of yeast phosphoglycerate kinase by Cr-ATP complexes and its implications on the conformation of the enzyme active site. 144 68

Three lipophilic amide derivatives of phthaloyl-GABA (P-GABA), namely gamma-phthalimido N-amyl butyramide (PGA), gamma-phthalimido-N-hexylbutyramide (PGH) and gamma-phthalimido N-phenylbutyramide (PGP), were synthesized and evaluated for their hypnotic and anticonvulsant activities in mice. Both PGA and PGH showed moderate hypnotic activity but PGP had no such action. Picrotoxin (0.08 mg/kg) a non-specific GABA antagonist completely abolished the hypnotic action of PGA in subconvulsive doses. Bicuculline (0.04 mg/kg) a GABAA antagonist, 3-mercaptopropionic acid (6 mg/kg) a GAD inhibitor at subconvulsive doses failed to neutralise the hypnotic action of PGA. On the other hand, PGA showed significant protection only against picrotoxin-induced convulsions, but was inactive against other convulsants tested. PGP which has no hypnotic activity, and has a mild anticonvulsant action in all the models except picrotoxin. A definite correlation was observed between the brain GABA and the hypnotic activity of PGA. However the present data indicate that the hypnotic and anticonvulsant activities are mediated probably through different brain GABA-ergic mechanisms.
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PMID:Neuropharmacology of amide derivatives of P-GABA. 145 30

The effect of nitrite ingestion on the intestinal deconjugation and absorption of folic acid (PGA) and brewers yeast folate was investigated using a rat bioassay and liver folate uptake as the response parameter. Male weanling Sprague Dawley rats were depleted on a low folate AIN-76A formulated basal diet for 21 days. During a 14 day repletion period, folic acid (PGA) and brewers yeast were added to provide 0.25, 0.5 and 1.0 mg of folate per kg of diet. Potassium nitrite was administered as part of the diet at 0.5%. All diets were made isonitrogenous and isocaloric. Based on a parallel line assay, the relative bioavailability of folate in the brewers yeast diet (109) was significantly higher than in the standard diet (PGA = 100). When combined with nitrite, the relative bioavailability of the PGA diet was not significantly different (101), while that of the brewers yeast diet was significantly lower than the standard diet. Concomitant ingestion of nitrite significantly reduced the bioavailability of brewers yeast folate but not that of PGA in rats. This appeared to be a direct effect of oxidation by nitrite on the more susceptible substituted folates in brewers yeast.
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PMID:Effect of nitrite ingestion on the bioavailability of folate in the rat. 147 6

According to the comparison of amino acid sequence between PGA (Penicillin G Acylase) and PBPs (Penicillin Binding Protein), We suggest that No. 565-595 peptide fragment in beta-subunit of PGA may be a substrate-binding site of enzyme. Plasmid pTZGA was constructed by cloning the 2.6 kb PGA gene of pWGA into phagemid pTZ18U The technique of site-specific mutagenesis was used to study the role of residue No. 579 (Ser) and No. 580 (Arg) of PGA. Four kinds of mutants were obtained (Ser579-->Gly579, Arg580-->Gly580, Arg580-->Glu580, Arg580-->Lys580), both Glu580 and Gly580 mutants showed no activity of enzyme and Lys580 mutant remained 30% and Gly579 mutant kept 70% activity of wilde type. The same protein expression of four mutants according to the results of ELISA indicate that mutation does not affect the expression of PGA, but Arg580 residue may be essential for substrate-binding or catalysis of PGA.
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PMID:[Studies on the function of Ser579 and Arg580 in beta-subunit of penicillin G acylase with the method of site-specific mutagenesis]. 147 18

The immunogenic potential of tetanus toxoid (TT) was compared when either adsorbed to aluminium hydroxide (TT-alum) or entrapped in microparticles consisting of poly(D,L-lactic-co-glycolic acid) (PLA:PGA, 55:45) derived polymers. Furthermore, the effect of administering the microparticles in an aqueous buffer or water-in-oil emulsion on the TT immunogenicity was also investigated. When mice were immunized with the different formulations, similar levels of anti-TT antibodies were observed during the primary IgG response. The choice of the carrier seemed to play an important role for both the level and maintenance of the secondary IgG response, attained as a consequence of a booster immunization with TT-alum. The strongest secondary antibody response was obtained by priming with TT-containing microparticles, resuspended in water-in-oil emulsions. As expected, incomplete Freund's adjuvant (IFA) proved to be a more potent adjuvant than peanut oil, whereas resuspension of the microparticles in aqueous solution induced a relatively less efficient antibody response. Overall, microencapsulated TT primed the mice more effectively, since the secondary antibody response was higher and persisted longer compared with TT-alum priming. These results indicate that in addition to TT maintaining its antigenicity after microencapsulation, the microparticles also potentiate its immunogenic properties. This approach should prove very useful for designing more effective vaccines.
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PMID:Parameters affecting the immunogenicity of microencapsulated tetanus toxoid. 152 81

The Pond-Nuki dog model of osteoarthritis has characteristics which seem to mimic the human disease in early stages, particularly with respect to progressive changes in the cartilage matrix. Aggregating proteoglycans were studied using novel extraction and ultracentrifugation methods designed to separate very large macromolecules. With these methods two large peaks of proteoglycan (PG) aggregates (PGA-1 and PGA-2) were separated in preparative amounts and were shown to have unequivocal differences in composition in many respects. The profiles of these peaks have been studied as a function of joint location, topographic site, cartilage layer, presence of cartilage atrophy versus osteoarthritis, as well as treatment of the animals with various agents. Both link protein (essential for forming link-protein stabilized aggregates) and hyaluronate are required to regenerate normal aggregate profiles from the deficient aggregate fractions obtained from osteoarthritic cartilage. Canine proteoglycan link-stabilized aggregates (PGA-2) are confined to the middle and deep zone of cartilage. We believe that their reduction or elimination in the Pond-Nuki model results from a disturbance or loss of functional link protein (and hyaluronate), thereby weakening the middle and deep cartilage layers.
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PMID:A mini review: proteoglycan aggregate profiles in the Pond-Nuki dog model of osteoarthritis and in canine disuse atrophy. 155 51

The effects of prostaglandins (PGs) A and J, which are anti-tumor eicosanoids, on the proliferation of cultured vascular smooth muscle cells were investigated. Serum-stimulated DNA synthesis was potently inhibited by PGA1, PGA2, PGJ2, and delta 12-PGJ2 in similar dose-dependent fashions. The effects of PGA1 and PGA2 were reversible when they were removed from the culture media, whereas recoveries were only partial in the cells treated with PGJ2 and delta 12-PGJ2. PGs were effective even if they were added immediately before entry into S phase. Inhibition of DNA synthesis was sustained when hydroxyurea, which blocks cell cycle at the G1/S border, was added after the removal of PGA2, and vice versa; PGs blocked DNA synthesis when they were added after the removal of hydroxyurea. Levels of c-myc mRNA formed two peaks during the G1 phase, at 1-2 h and at 8-12 h. The PGs did not affect the first elevation, but enhanced the second and sustained it up to 18-24 h, whereas in controls, c-myc mRNA decreased quickly after entry into S phase. The rate of degradation of c-myc mRNA was much smaller in PG-treated cells than in nontreated cells. We conclude, therefore, that PGA and PGJ inhibit a crucial event(s) in the cell cycle occurring at the G1/S border, but that this inhibition is not accompanied by the reduction in c-myc gene expression in contrast with some types of tumor cells treated with PGs.
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PMID:Prostaglandins A and J arrest the cell cycle of cultured vascular smooth muscle cells without suppression of c-myc expression. 157 2


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