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C Wilder

Publications and source records attributed to C Wilder.

8 recordsLinked to original sources
PubMed2001

Platelet-activating factor acetylhydrolases: broad substrate specificity and lipoprotein binding does not modulate the catalytic properties of the plasma enzyme.

Platelet-activating factor acetylhydrolases (PAF-AHs) are a group of enzymes that hydrolyze the sn-2 acetyl ester of PAF (phospholipase A(2) activity) but not phospholipids with two long fatty acyl groups. Our previous studies showed that membrane-bound human plasma PAF-AH (pPAF-AH) accesses its substrate only from the aqueous phase, which raises the possibility that this enzyme can hydrolyze a variety of lipid esters that are partially soluble in the aqueous phase. Here we show that pPAF-AH has broad substrate specificity in that it hydrolyzes short-chain diacylglycerols, triacylglycerols, and acetylated alkanols, and displays phospholipase A(1) activity. On the basis of all of the substrate specificity results, it appears that the minimal structural requirement for a good pPAF-AH substrate is the portion of a glyceride derivative that includes an sn-2 ester and a reasonably hydrophobic chain in the position occupied by the sn-1 chain. In vivo, pPAF-AH is bound to high and low density lipoproteins, and we show that the apparent maximal velocity for this enzyme is not influenced by lipoprotein binding and that the enzyme hydrolyzes tributyroylglycerol as well as the recombinant pPAF-AH does. Broad substrate specificity is also observed for the structurally homologous PAF-AH which occurs intracellularly [PAF-AH(II)] as well as for the PAF-AH from the lower eukaryote Physarum polycephalum although pPAF-AH and PAF-AH(II) tolerate the removal of the sn-3 headgroup better than the PAF-AH from P. polycephalum does. In contrast, the intracellular PAF-AH found in mammalian brain [PAF-AH(Ib) alpha 1/alpha 1 and alpha 2/alpha 2 homodimers] is more selectively operative on compounds with a short acetyl chain although this enzyme also displays significant phospholipase A(1) activity.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2000

Agreement among three quality of life measures in patients with ALS.

AIM: To determine the concurrent validity of three self-administered health-related quality of life (HRQOL) questionnaires when administered to patients with amyotrophic lateral sclerosis (ALS). BACKGROUND: ALS is the most common motor neuron disease among adults. As a rapidly progressive and fatal disease, ALS has devastating effects on the patient's relationships, functional capacity and mental health. HRQOL measures include information about patients' physical impairments, functional level, and psychosocial status. This study compares a tool designed for the ALS population, the Sickness Impact Profile ALS-19 (SIP/ALS19), and two tools designed to be used in any population, the Quality of Well-being Scale SA (QWB SA), and the SF-36 Health Survey (SF-36). Correlation of the scores would suggest that each tool is valid as a stand-alone measurement of quality of life for this patient population. METHODS: The SIP/ALS-19, the SF-36, and the QWB SA were self-administered to 19 subjects diagnosed with ALS. The scores for each test were ranked and analyzed for agreement using the Spearman rank correlation coefficient. RESULTS: The SIP/ALS-19 demonstrated moderate to good correlation with the QWB SA and fair correlation with the SF-36. The SF-36 had little to no correlation with the QWB SA. CONCLUSIONS: The study did not demonstrate significant correlation among the three quality of life measures. The SIP/ALS-19, SF-36, and QWB SA each have a different focus in measuring HRQOL. The healthcare practitioner should consider the patient's stage of disease, treatment goals, and type of interventions planned when selecting a HRQOL tool for the ALS patient.

Adult↗
PubMed1999

Membrane-bound plasma platelet activating factor acetylhydrolase acts on substrate in the aqueous phase.

Human plasma platelet activating factor acetylhydrolase (pPAF-AH) is a phospholipase A(2) that specifically hydrolyzes the sn-2 ester of platelet activating factor (PAF) and of phospholipids with oxidatively truncated sn-2 fatty acyl chains. pPAF-AH is bound to lipoproteins in vivo, and it binds essentially irreversibly to anionic and zwitterionic phospholipid vesicles in vitro and hydrolyzes PAF and PAF analogues. Substrate hydrolysis also occurs in the absence of vesicles, with a maximum rate reached at the critical micelle concentration. A novel pre-steady-state kinetic analysis with enzyme tightly bound to vesicles and with a substrate that undergoes slow intervesicle exchange establishes that pPAF-AH accesses its substrate from the aqueous phase and thus is not an interfacial enzyme. Such a mechanism readily explains why this enzyme displays dramatic specificity for phospholipids with short sn-2 chains or with medium-length, oxidatively truncated sn-2 chains since a common feature of these lipids is their relatively high water solubility. It also explains why the enzymatic rate drops as the length of the sn-1 chain is increased. pPAF-AH shows broad specificity toward phospholipids with different polar headgroups. Additional results are that PAF undergoes intervesicle exchange on the subminute time scale and it does not undergo transbilayer movement over tens of minutes.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1995

Anti-inflammatory properties of a platelet-activating factor acetylhydrolase.

Platelet-activating factor (PAF) is a potent pro-inflammatory phospholipid that activates cells involved in inflammation. The biological activity of PAF depends on its structural features, namely an ether linkage at the sn-1 position and an acetate group at the sn-2 position. The actions of PAF are abolished by hydrolysis of the acetyl residue, a reaction catalysed by PAF acetylhydrolase. There are at least two forms of this enzyme--one intracellular and another that circulates in plasma and is likely to regulate inflammation. Here we report the molecular cloning and characterization of the human plasma PAF acetylhydrolase. The unique sequence contains a Gly-Xaa-Ser-Xaa-Gly motif commonly found in lipases. Recombinant PAF acetylhydrolase has the substrate specificity and lipoprotein association of the native enzyme, and blocks inflammation in vivo: it markedly decreases vascular leakage in pleurisy and paw oedema, suggesting that PAF acetylhydrolase might be a useful therapy for severe acute inflammation.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗