Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

PAF-acether (PAF) is a phospholipid mediator with potent biological effects on the digestive tract. We report the presence of PAF in stool of patients with active Crohn's disease (39.1 +/- 13.5 ng/g of stool, mean +/- SEM, N = 19) and its absence in patients with irritable bowel syndrome with diarrhea and diarrhea with malabsorption. Fecal PAF acetylhydrolase activity was higher (P less than 0.04) in patients with Crohn's disease as compared to patients with irritable bowel syndrome with diarrhea and diarrhea with malabsorption. We also report a solid-phase extraction of fecal PAF using silica minicolumns, which yielded results highly correlated with those obtained with a high-performance liquid chromatography method (r = 0.86, P less than 0.001, N = 16). These findings may allow us to implicate PAF in the onset and perpetuation of digestive tract inflammatory symptoms observed during Crohn's disease. They would warrant to investigate the influence of various therapeutic agents, including PAF antagonists, on fecal PAF levels during inflammatory digestive ailments.
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PMID:PAF-acether and acetylhydrolase in stool of patients with Crohn's disease. 173 66

The inactivation of the biologically active ether-containing glycerophospholipid platelet-activating factor (PAF) is catalyzed by the enzyme PAF acetylhydrolase (1-alkyl-2-acetyl-sn-glycero-3-phosphocholine acetylhydrolase, EC 3.1.1.48). The specific activity of acetylhydrolase has been assayed in maternal rabbit plasma prior to and throughout pregnancy and after parturition. The specific activity of acetylhydrolase was 131 +/- 8 nmol.min-1.ml-1 of plasma (mean +/- SEM) in the nonpregnant rabbit. Similar specific activities were found throughout the first half of pregnancy; however, on day 15 the acetylhydrolase activity began to decrease and reached a minimum around day 27. Within 24-48 hr following delivery, the specific activity of the enzyme increased to the levels found in the nonpregnant animals. The specific activity of acetylhydrolase in fetuses (gestational ages of 21-30 days) and neonates increased from 22 nmol.min-1.ml-1 of plasma (21-day-old) to 328 nmol.min-1.ml-1 of plasma (35-day-old rabbits). The decrease in enzymatic activity of the pregnant rabbit plasma cannot be accounted for by the presence of an inhibitor as determined by plasma-mixing experiments with nonpregnant and pregnant (27-day) plasma. The properties of this enzyme in the rabbit were consistent with those reported by others, i.e., substrate specificity, inactivation by heat and various inhibitors, and Ca2+ independency. The activity of PAF acetylhydrolase was associated primarily with the high density lipoprotein fraction in rabbit plasma. The decrease of this enzymatic activity during pregnancy may serve to remove the protective effect on myometrium to allow an increased amount of PAF to come in contact with this tissue.
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PMID:Platelet-activating factor acetylhydrolase activity in maternal, fetal, and newborn rabbit plasma during pregnancy and lactation. 342 55

Platelet-activating factor (PAF), as well as PAF acetylhydrolase (PAF-AH) activity in the peripheral blood plasma of patients with psoriasis and palmoplantar pustolosis, was measured with a radioimmunoassay technique, and compared with leukotriene (LT) B4, LTC4, LTD4 and E4 (LTD4/E4), thromboxane (TX) B2 and prostaglandin (PG) E2 levels. In a normal healthy group (n = 12) PAF level was 25.9 +/- 6.5 pg/0.1 ml plasma (mean +/- standard error of the mean: SEM), and this was elevated in patients with psoriasis (68.1 +/- 11.8, n = 25, P < 0.01), without a change in the PAF-AH level. LTB4 showed a similar increase (115.0 +/- 21.6 pg/ml vs. 68.2 +/- 11.8 pg/ml, P < 0.05), while TXB2 and PGE2 showed insignificant (P > 0.05) changes. LTC4 and LTD4/E4 were around the level of the limit of detection. Patients with palmoplantar pustulosis (n = 33) demonstrated similar, but milder and statistically insignificant, increases in PAF, LTB4, TXB2 and PGE2 levels. Modulation of the mediator levels before and after treatment was compared in 16 patients with psoriasis and 11 with palmoplantar pustulosis. PAF in psoriasis significantly decreased after treatment (70.9 +/- 17.1 to 25.1 +/- 5.5, P < 0.05) and this was moderately correlated (r = 0.298) with clinical improvement as indicated by the psoriasis area and severity index (38.5 +/- 7.5 to 10.9 +/- 4.2, P < 0.01). TXB2 (180.2 +/- 100.4 to 34.1 +/- 13.5), PGE2 (3.7 +/- 0.7 to 2.9 +/- 0.5) and LTB4 (120.1 +/- 31.1 to 84.2 +/- 8.2), in psoriasis, mildly decreased without statistical significance. Patients with palmoplantar pustulosis demonstrated a similar decrease in all mediators without statistical significance. The results obtained suggest a role of PAF in psoriasis. As the priming effects of PAF have been shown, for leucocytes and endothelial cells, to enhance their inflammatory response, we assume that PAF has roles in the acute phase of psoriatic and leucotactic inflammation.
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PMID:Platelet-activating factor and arachidonic acid metabolites in psoriatic inflammation. 911 38

The role of platelet-activating factor (PAF) in the pathogenesis of microvascular vaso-occlusion in sickle cell disease (SCD) is not known. In order to assess a role for PAF in vaso-occlusion in patients with SCD in steady state conditions, we measured plasma PAF level and plasma PAF acetylhydrolase activity as indices of PAF metabolism in vivo. We also studied PAF synthesis, from (3H)-acetate, by purified platelets stimulated with A23187. PAF was extracted from plasma of ten patients with SCD in steady state and from age-matched controls. PAF, purified by thin-layer chromatography, was quantitated by radioimmunoassay. PAF level (mean +/- SEM, pg/ml) in plasma of controls was 393 +/- 65, which was significantly lower than the 797 +/- 62 measured in plasma of patients with SCD. There was no difference in acetylhydrolase activity between the two groups. PAF synthesis (mean +/- SEM, nmol/10(6) cells) by platelets of controls without exogenous lyso-PAF was 1.69 +/- 0.24, higher than the 0.59 +/- 0.038 synthesized by platelets of patients with SCD. Incubation of platelets with 1.0 micromol/L lyso-PAF increased PAF synthesis by controls to 8.93 +/- 1.76, still higher than the 4.59 +/- 0.98 synthesized by platelets of patients with SCD. Our data show that patients with SCD are susceptible to a higher circulating levels of PAF in vivo during steady-state conditions. We speculate that higher levels of PAF may be a contributing factor to the persistent stress and inflammatory state of the microcirculation of patients with SCD.
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PMID:Platelet-activating factor in plasma of patients with sickle cell disease in steady state. 928 Jan 46

We recently showed that platelet activating factor (PAF) is an important modulator of pulmonary vasomotor tone in the fetus, with a significant decrease in circulating PAF levels in the immediate newborn period. In this study, we have determined PAF catabolism by PAF acetylhydrolase (PAF-Ah) in lungs of near-term fetal and newborn 2- to 16-h (<1 day) and 6- to 12-day-old lambs. The rate of PAF catabolism by lung homogenate protein from the three groups of lamb lungs was studied at 37 degrees C in 30 mM Tris buffer, pH 7.5, containing 0.01% BSA. Each lung homogenate protein was incubated for 10 min with 50 microM [(3)H]acetyl-PAF at pO(2) <50 Torr (hypoxia) and approximately 100 Torr (normoxia). PAF-Ah activity was quantified as amount of lyso-PAF produced. PAF-Ah activity (means +/- SEM, nmol lyso-PAF/min/mg protein) in fetal lung homogenate was 1.19 +/- 0.14 and 2.46 +/- 0.05 during hypoxia and normoxia, respectively. The corresponding values for the newborns were newborn <1 day, 1.65 +/- 0.26 and 2.95 +/- 0.07 and newborn 6-12 days, 1.25 +/- 0.10 and 2.84 +/- 0.05. In all groups, PAF-Ah activity was higher in normoxia than in hypoxia. During normoxia, PAF-Ah activity in newborn <1 day was significantly higher than the activity in fetus, but similar to the activity in newborn 6- to 12-day-old lamb lungs. These data show a significant up-regulation of PAF-Ah activity in lungs in the immediate newborn period. PAF-Ah gene expression measured by RT-PCR showed a significant up-regulation of the PAF-Ah gene in lungs of lambs <1 day old, suggesting a transcriptional regulation of the PAF-Ah gene in the immediate newborn period. These results suggest that up-regulation of PAF-Ah activity after birth with oxygenation will result in a decrease in circulating PAF levels, thereby facilitating the fall in pulmonary vascular resistance in the immediate newborn period.
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PMID:Platelet activating factor acetylhydrolase activity in lamb lungs is up-regulated in the immediate newborn period. 1065 57

We recently reported that PAF acetylhydrolase (PAF-Ah) mRNA level and PAF-Ah activity in lamb lungs are up-regulated in the immediate newborn period, thereby facilitating the fall in postnatal PAF levels as well as a fall in pulmonary vascular resistance (B. O. Ibe, F. C. Sardar, and J. U. Raj, Mol Genet Metab 69:46-55, 2000). We have studied hypoxia effects on PAF synthesis and PAF-Ah activity in fetal lamb pulmonary arterial smooth muscle cells (FPASMC) and endothelial cells (FPAEC). We also studied PAF synthesis by platelets, and PAF-Ah activity in plasma of perinatal lambs at different ages. PAF synthesis (means +/- SEM, pmol/10(6) cells) by SMC in baseline was 168 +/- 27 and increased 3-fold on stimulation with A23187. Hypoxia augmented A23187-stimulated PAF synthesis by 30%. In FPAEC, baseline synthesis was 0.54 +/- 0.062 and increased 3-fold to 1.72 +/-.34. Hypoxia had no effect on PAF synthesis by EC. FPASMC produced over 300-fold more PAF than FPAEC. PAF synthesis by platelets was 47.02 +/- 7.1, 63.4 +/- 6.6, 71.5 +/- 9.9, and 62.2 +/- 5.2 for fetal, and newborn lambs <2 h, <1 day, and 6-12 days, old, respectively. PAF synthesis by platelets of <1 day-old lambs was different from that of fetal lambs. PAF-Ah activity (nmol lyso-PAF/min/mg protein) by FPASMC in normoxia was 3.41 +/- 0.38 which was 50% higher than the rate in hypoxia. Activity in FPAEC was 1.75 +/- 0.37 which was not different from hypoxia. PAF-Ah activity in fetal lamb plasma was 47.83 +/- 6.87 which was different from 155.32 +/- 12.10, the activity in plasma of newborn <1 day old. Activity in the other perinatal lambs did not differ from fetal or newborn <1 d. Our data suggest that lower pulmonary vascular PAF synthesis in normoxia together with higher PAF-Ah activity during immediate postnatal period is necessary to ensure rapid catabolism of PAF in vivo so as to facilitate postnatal adaptation of the pulmonary and systemic circulations.
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PMID:Maturational changes in ovine pulmonary metabolism of platelet-activating factor: implications for postnatal adaptation. 1170 70