Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aspergillus niger pectin lyases are encoded by a multigene family. The complete nucleotide sequence of the pectin lyase PLA-encoding gene pelA has been determined. Comparison of the deduced amino acid sequence with the deduced amino acid sequence of the other characterized pectin lyase, PLD, shows that the proteins share 69% amino acid identity. When grown on media with pectin as the sole carbon source, A. niger transformants containing multiple copies of the pelA gene show raised mRNA levels and overexpression of the gene product PLA compared with the wild-type strain. PLA was purified and characterized. In A. nidulans transformants PLA is also produced in medium containing a high concentration of glucose and no pectin.
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PMID:Structure of the Aspergillus niger pelA gene and its expression in Aspergillus niger and Aspergillus nidulans. 193 34

Biodegradable Poly(L-lactic acid) microspheres containing neutron-activable 165Ho were designed for internal radiation therapy of hepatic tumors. Spheres composed of Poly(L-lactic acid) (PLA) were prepared with excellent reproducibility containing up to 36% of a holmium complex. The prepared spheres were irradiated in a high neutron flux converting 165Ho to 166Ho (Emax = 1.84 MeV, half-life = 26.9 hr). Thus, these microspheres can be prepared under conditions that do not require the handling of a hazardous radionuclide, and then irradiated just prior to administration. In vitro studies in plasma (n = 6) revealed 97.3% (+/- 1.9) retention of 166Ho in the microspheres after 240 hr. PLA spheres administered via the portal vein in rabbits (n = 6) show 94.5% (+/- 3.4) retention of the original 166Ho activity in the liver after 6 days.
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PMID:Neutron-activated holmium-166-poly (L-lactic acid) microspheres: a potential agent for the internal radiation therapy of hepatic tumors. 194 Nov 51

In the critically ill, accurate measurements of left ventricular (LV) filling pressure using pulmonary artery occlusion pressure (Ppao) are important for diagnostic and therapeutic purposes. In patients receiving positive end-expiratory pressure (PEEP), Ppao may not reflect LV filling pressure because of elevated pericardial pressure (Ppc). It has been proposed that in humans, Ppc and right atrial pressure (PRA) are equal, so that referencing Ppao to PRA may improve the assessment of LV filling pressure when Ppc is elevated. Similarly, it has also been shown in the dog that nadir Ppao immediately after airway disconnection from PEEP (nadir Ppao), accurately reflects LV filling pressure when LV filling pressure is greater than or equal to 10 mm Hg. We examined methods of estimating LV filling pressure using Ppao measurements under conditions in which increases in Ppc were the primary determinants of differences in the two measurements. Using left atrial pressure (PLA) relative to Ppc, called transmural PLA (PLAtm), as LV filling pressure, we compared the accuracy of Ppao, nadir Ppao, and Ppao relative to PRA to reflect PLAtm in 15 postoperative cardiac surgery patients in whom an air-filled pericardial balloon catheter and a left atrial catheter were inserted during surgery. PEEP was sequentially increased from zero to 15 cm H2O. We found that PRA always exceeded Ppc (p less than 0.01) and increased less with PEEP than did Ppc (p less than 0.05). At less than or equal to 5 cm H2O PEEP, both Ppao and nadir Ppao were similar to each other and to PLAtm.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Estimating left ventricular filling pressure during positive end-expiratory pressure in humans. 192 77

Arachidonic acid increased the outputs of prostaglandin (PG) F-2 alpha, PGE-2 and 6-keto-PGF-1 alpha from the Day-7 and Day-15 guinea-pig uterus superfused in vitro. Similar increases in PG output were observed when the arachidonic acid treatment was repeated after an interval of 1, 3 or 5 h. Phospholipase (PL) A-2 increased the outputs of PGF-2 alpha, PGE-2 and 6-keto-PGF-1 alpha from the Day-7 guinea-pig uterus, but repeating the PLA-2 treatment 1 h later failed to stimulate PG output. The increase in outputs of PGF-2 alpha and PGE-2 caused by PLA-2 were partly restored after 3 h and were fully restored after 5 h, whereas the increase in 6-keto-PGF-1 alpha output produced by PLA-2 was only partly restored after 3 and 5 h. PLA-2 had little or no effect on PGF-2 alpha and PGE-2 outputs from the Day-15 guinea-pig uterus initially, and when repeated after 1, 3 and 5 h. This was probably due to the output of these two PGs, particularly of PGF-2 alpha, being stimulated in vivo before removal of the uterus. PLA-2 increased 6-keto-PGF-1 alpha output from the Day-15 uterus initially, but failed to cause a response when administered again 1 h later. After 3 and 5 h, the increase in 6-keto-PGF-1 alpha output from the Day-15 uterus caused by PLA-2 was partly restored. A23187 and PLC increased the outputs of PGF-2 alpha, PGE-2 and 6-keto-PGF-1 alpha from the Day-7 and Day-15 guinea-pig uterus. These responses to A23187 and PLC were reduced (but not abolished) when the two compounds were administered again 1 h later. After 3 and 5 h, the increases in output of PGF-2 alpha and PGE-2 produced by A23187 and PLC had returned to the initial values. The increases in output of 6-keto-PGF-1 alpha from the Day-7 and Day-15 guinea-pig uterus produced by A23187 and PLC were partly restored after 3 and 5 h, except for the response to PLC on Day 7 which was fully restored after 5 h. The results show that there is no failure with time in the mechanism which converts arachidonic acid into PGF-2 alpha in the guinea-pig uterus.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:A possible explanation for the refractoriness of uterine prostaglandin production. 199 60

Phospholipases A2 (PLA-2) are conserved enzymes that can vary widely in their activity toward certain biological targets. Activity of PLA-2 toward Escherichia coli treated with the bactericidal/permeability-increasing protein (BPI) of granulocytes has been detected only in "Group II" PLA-2 (lacking Cys11-Cys77) and correlates with overall basicity and the presence of a cluster of basic amino acids within a variable surface region near the NH2 terminus (including residues 6, 7, 10, 11, and 15). We now show that of five pancreatic PLA-2 ("Group I" enzymes) tested from different species of mammals, the human enzyme that is most basic both globally (pI 8.7) and locally (Arg-6, Lys-7, and Lys-10) is active toward BPI-treated E. coli (approximately 1-2% activity of the most active Group II PLA-2) whereas the other four PLA-2 are essentially inactive (less than 0.1%). The cDNA of the pig pancreatic PLA-2 (pI 6.4; Arg-6, Ser-7, Lys-10) has been modified by site-specific mutagenesis and the wild-type and mutant PLA-2 have been expressed in and purified from either E. coli or Saccharomyces cerevisiae to determine more precisely the structural determinants of PLA-2 activity toward BPI-treated E. coli. The single substitution of lysine (or arginine) for Ser-7 transformed the pig pancreatic PLA-2 into an active enzyme toward BPI-treated E. coli possessing 25-50% the activity of the human PLA-2. Additional modifications to increase global basicity (increase in net charge up to +4) caused a further (up to 2-fold) increase in activity. All mutant PLA-2 still containing Ser-7 possessed little or no activity toward BPI-treated E. coli. Changes in activity toward BPI-treated E. coli were accompanied by parallel changes in enzyme binding to this target. In contrast, substitution of lysine (or arginine) for Ser-7 caused little or no alteration of enzyme activity toward either autoclaved E. coli or egg yolk lipoproteins indicating no major effects on the catalytic properties of the PLA-2. This study demonstrates directly the role of NH2-terminal basic residues in the action of PLA-2 on BPI-treated E. coli and suggests that these properties mainly facilitate PLA-2 binding to this biological target.
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PMID:Conversion of pig pancreas phospholipase A2 by protein engineering into enzyme active against Escherichia coli treated with the bactericidal/permeability-increasing protein. 199 11

The solution structure of porcine pancreatic phospholipase A2 (124 residues, 14 kDa) has been studied by two-dimensional homonuclear 1H and two- and three-dimensional heteronuclear 15N-1H nuclear magnetic resonance spectroscopy. Backbone assignments were made for 117 of the 124 amino acids. Short-range nuclear Overhauser effect (NOE) data show three alpha-helices from residues 1-13, 40-58, and 90-109, an antiparallel beta-sheet for residues 74-85, and a small antiparallel beta-sheet between residues 25-26 and 115-116. A 15N-1H heteronuclear multiple-quantum correlation experiment was used to monitor amide proton exchange over a period of 22 h. In total, 61 amide protons showed slow or intermediate exchange, 46 of which are located in the three large helices. Helix 90-109 was found to be considerably more stable than the other helices. For the beta-sheets, four hydrogen bonds could be identified. The secondary structure of porcine PLA in solution, as deduced from NMR, is basically the same as the structure of porcine PLA in the crystalline state. Differences were found in the following regions, however. Residues 1-6 in the first alpha-helix are less structured in solution than in the crystal structure. Whereas in the crystal structure residues 24-29 are involved both in a beta-sheet with residues 115-117 and in a hairpin turn, the expected hydrogen bonds between residues 24-117 and 25-29 do not show slow exchange behavior. This and the absence of several expected NOEs imply that this region has a less well defined structure in solution. Finally, the hydrogen bond between residues 78-81, which is part of a beta-sheet, does not show slow exchange behavior.
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PMID:Porcine pancreatic phospholipase A2: sequence-specific 1H and 15N NMR assignments and secondary structure. 200 45

Eighteen patients with acute pancreatitis(AP) were studied prospectively with a clinical analysis of 34 patients with ARDS caused by AHP. Ten of the 18 AP patients had lung damage demonstrated by PaO2 and P (A-a) O2, in which the elevation of the blood and alveolar levels of FFA and PLA also contributed to the pathogenesis of lung damage and ARDS. The 34 ARDS patients could be divided into 3 groups according to the speed with which ARDS developed, i.e. rapid, postoperatively rapid, and delayed occurring. It was also found that the mortality rate of ARDS was closely related to the number of organs involved in AHP. We suggested 8 risk factors of ARDS in AHP cases and discussed the etiology of ARDS, its early diagnosis, prophylaxis, and management.
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PMID:[Adult respiratory distress syndrome as a complication of acute hemorrhagic pancreatitis]. 203 7

The Escherichia coli outer-membrane phospholipase A (OM PLA) is a membrane-bound acyl hydrolase with a broad substrate specificity. In order to obtain more insight into the mechanism of action of this enzyme, we designed an active-site-directed inhibitor for OM PLA on the basis of the known substrate specificity as a first step in the elucidation of the catalytic mechanism of this enzyme. The inhibitor, hexadecanesulfonyl fluoride, consists of a long hydrocarbon chain for high-affinity binding by the enzyme and a sulfonyl fluoride moiety as a reactive group. The kinetics of the inactivation of OM PLA by hexadecanesulfonyl fluoride were studied in Triton X-100 micelles. Inactivation is very fast, specific and shows the same characteristics with respect to acyl specificity, pH profile and metal ion requirement as the activity of OM PLA on substrates. Incubation of OM PLA with a stoichiometric amount of hexadecanesulfonyl fluoride leads to a total and irreversible loss of enzyme activity, resulting from the sulfonylation of Ser144. This Ser144, which we suggest to be the active-site serine of OM PLA, is part of the sequence HDSNG, whereas in the water-soluble serine proteases and lipases the structural motif GXSXG is normally encountered. On the basis of the kinetics of inactivation of OM PLA by hexadecanesulfonyl fluoride, we discuss a possible catalytic mechanism of the enzyme.
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PMID:Inactivation of Escherichia coli outer-membrane phospholipase A by the affinity label hexadecanesulfonyl fluoride. Evidence for an active-site serine. 204 Feb 86

The activity of the Escherichia coli outer-membrane phospholipase (OM PLA) is strictly regulated in its natural habitat, the E. coli outer membrane. OM PLA can be reconstituted in phospholipid bilayers, resulting in low specific activity of the enzyme compared to its activity on mixed lipid/detergent micelles. The enzyme can be activated by the addition to these vesicles of the membrane-perturbing peptides polymyxin B, melittin or cardiotoxin resulting in hydrolysis of mainly the sn-1 ester bond of the phospholipids as is also observed in vivo. We used the affinity label hexadecanesulfonyl fluoride to probe the influence of lipid environment on the activity of OM PLA. In detergent and substrate micelles, the rate constant for the sulfonylation of the active-center serine of the purified OM PLA by the affinity label hexadecanesulfonyl fluoride depends on amphiphile concentration. We have reported a similar influence of amphiphile concentration on the activity of the enzyme [Horrevoets, A. J. G. et al. (1989) Biochemistry 28, 1139-1147]. Analysis of the rates of inactivation of OM PLA by hexadecanesulfonyl fluoride in vesicles composed of various phospholipids indicated that activation of the enzyme by membrane-perturbing peptides can be accurately quantified with this affinity label. Our results show that the affinity label hexadecanesulfonyl fluoride can be used to monitor the state of activation of OM PLA in different lipid environments, including non-hydrolyzable substrate analogues. Implications for the in vivo situation are discussed.
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PMID:Activation of reconstituted Escherichia coli outer-membrane phospholipase A by membrane-perturbing peptides results in an increased reactivity towards the affinity label hexadecanesulfonyl fluoride. 204 Feb 88

Allo-immune neonatal thrombopenia is to platelets what rhesus hemolytic disease is to red blood cells. There is a risk of haemorrhage when fetal platelets decreases below 50,000 per mm3. Such haemorrhage may occur at any time during the thrombopenia period. However they are mostly due to obstetrical traumatisms during delivery. Lethal complications and severe neurologic sequellae is estimated to affect about 30% of newborns: 1/3 these complications occur in utero and 2/3 during delivery. The authors have studied 3 familial cases of foeto-maternal allo-immunisation occurring with the PLA 1 system. They have made a briefing of the physiological, the pathological and the epidemiological aspects of such immunisation before insisting upon case findings of such affected fetus. A capillary blood sample taken from the scalp of the fetus at the beginning of labour allows a safe natural delivery if fetal blood count shows more than 50,000 platelets per mm3. A fetal blood sampling under ultrasonographic guidance will bring about to an early diagnosis and prognosis, this allowing an adequate treatment for fetus with a high risk of thrombopenia.
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PMID:[Neonatal alloimmune thrombocytopenia following immunization against the platelet antigen ZWA (PLA/1). 3 case reports in the same family and analysis of the literature]. 208 61


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