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Biomedical subjects

Y Denizot

Publications and source records attributed to Y Denizot.

At least 109 records · Page 6Linked to original sources
PubMed1992

Raised concentrations of platelet activating factor in colonic mucosa of Crohn's disease patients.

Platelet activating factor (PAF-ACETHER or PAF) and precursors of platelet activating factor were investigated in 26 patients with acute Crohn's disease and in 10 healthy controls. Platelet activating factor, lyso platelet activating factor, and alkyl acyl glycerophosphocholine, were determined in colonic mucosal biopsies in patients with acute Crohn's disease, during prednisolone therapy, and in remission. Biopsy specimens were submitted to histopathology examination and to phospholipid extraction. Platelet activating factor, lyso platelet activating factor, and alkyl acyl glycerophosphocholine were found in patients with acute Crohn's disease and in remission as well as in controls. Whatever the site of the biopsy, the level of platelet activating factor in colonic mucosa was higher (p < 0.01) in Crohn's disease than in controls. There was no correlation between the level of colonic PAF-ACETHER and age, sex, Crohn's disease activity index, and biological parameters in sera. Although concentrations of colonic platelet activating factor content were higher (p < 0.01) when colonic mucosa displayed cell infiltration, they were neither related to the severity nor the type of inflammatory cells. Platelet activating factor decreases with prednisolone therapy and might return to normal concentrations in quiescent patients. Lyso platelet activating factor and alkyl acyl glycerophosphocholine were not significantly higher in Crohn's disease than in controls. These data suggest that platelet activating factor may be involved in the pathogenesis of Crohn's disease and that it could be used as a marker of the mucosal activity of the disease.

Adult↗
PubMed1991

Paf-acether in human skin.

Paf is a phospholipid mediator present in human skin which induces inflammatory events, such as neutrophil infiltration and increased vascular permeability. Recent data suggest that cutaneous cells, such as fibroblasts and keratinocytes, produce paf and that paf is released during allergic cutaneous reactions. It is tempting to speculate that paf may contribute to the development of various skin disorders with acute and chronic skin inflammation. Paf antagonists may help in bringing answers to this hypothesis and may offer new prospects for the treatment of cutaneous inflammatory diseases.

Humans↗
PubMed1991

Presence of PAF-acether in stool of patients with pouch ileoanal anastomosis and pouchitis.

Platelet-activating factor is an endogenous phospholipid produced by a wide variety of inflammatory cells. Platelet-activating factor induces severe pathological changes in various organs and, among numerous potent effects, causes bowel necrosis. Pouchitis is a poorly understood complication of ileoanal pouch anastomosis which occurs in patients who undergo surgery for ulcerative colitis. The aim of this study was to measure ileal or fecal platelet-activating factor and lyso platelet-activating factor contents in normal volunteers (n = 12), in patients with terminal ileostomy (n = 7), and in patients with ileoanal anastomosis (n = 15) (8 patients have pouchitis defined by the presence of ulcerations on the reservoir). Fecal samples were processed and assessed for platelet-activating factor by platelet aggregation assay. The aggregating material was further characterized as platelet-activating factor by the following: inhibition of the platelet aggregation it induced by specific platelet-activating factor receptor antagonist (BN 52021; IHB, Le Plessis Robinson, France); abolition of platelet aggregation after incubation with phospholipase A2 but not with lipase A1; and retention time on high-performance liquid chromatography. Stool platelet-activating factor content (in nanograms per gram of stool, mean +/- 1SD) was significantly increased in patients with pouchitis (22.2 +/- 16 ng/g) compared with patients with normal reservoir (1.59 +/- 0.63 ng/g, P less than 0.01), terminal ileostomy (0.59 +/- 0.43 ng/g, P less than 0.01), and healthy controls (0 +/- 0 ng/g of stool, P less than 0.001). Lyso platelet-activating factor (nanograms per gram of stool) was increased in patients with pouchitis (10,704 +/- 5499 ng/g) compared with patients with normal reservoir (4721 +/- 4549 ng/g of stool, P less than 0.05), terminal ileostomy (3042 +/- 4019 ng/g, P less than 0.02), and healthy volunteers (128 +/- 107 ng/g, P less than 0.001). In patients with ileoanal anastomosis and pouchitis, increased platelet-activating factor production could be implicated in the inflammation and ulcerations observed in the reservoir.

Adult↗
PubMed1991

[Presence paf-acether mediator of inflammation in stools of patients with inflammatory enterocolitis].

Paf-acether (platelet-activating factor, paf) is one of the most potent inflammatory mediators synthesised by and acting on most inflammatory cells. Paf causes gastric ulcerations and ischemic bowel necrosis. Recently, we described the presence of paf in stools of patients bearing ileal pouch-anal anastomosis with pouchitis. These findings prompted us to search for the presence of paf in stools of patients suffering from inflammatory bowel diseases: Crohn's disease and ulcerative colitis. The fraction corresponding to paf isolated from stools exhibited the same physicochemical and biological characteristics as synthetic paf. Reverse-phase high performance liquid chromatography revealed 80% of C16 and 20% of C18 paf. The presence of a biologically active phospholipid in human stools may bring new perspectives with respect to the study of gastrointestinal diseases as well as the use of paf antagonists in the treatment of inflammatory bowel diseases.

Chromatography, High Pressure Liquid↗
PubMed1991

["Pouchitis" after ileo-anal anastomosis with reservoir].

Pouchitis is the most poorly understood complication of ileoanal anastomosis. The incidence reported in the literature ranges from 7 to 42% as there are no diagnostic criteria. The various clinical symptoms and endoscopic findings raise the possibility that pouchitis is a heterogenous disease, in which the role of bacterial overgrowth and recurrence of inflammatory bowel disease must be clarified.

Acute Disease↗
PubMed1990

Immunoregulatory functions of paf-acether. IV. Enhancement of IL-1 production by muramyl dipeptide-stimulated monocytes.

paf-Acether (paf) is a phospholipid mediator of inflammation released from monocytes along with IL-1. In this study, we have examined the role of paf on IL-1 production by human monocytes. When paf from 1 nM to 5 microM, but not its precursor lyso paf, was added to monocytes in the presence of muramyl dipeptide (MDP) or LPS, a marked increase in IL-1 activity over the value with MDP alone was observed. In contrast, paf alone had minimal activity over the same dose range. Antibodies against rHu IL-1 alpha and rHu IL-1 beta neutralized the increased IL-1 activity. Interestingly, MDP that prompts monocytes to synthesize IL-1, induced the synthesis of paf, as well. Most of the paf produced remained cell-associated and always preceded IL-1 synthesis. When the paf receptor antagonist, L-652,731 was added to monocytes, it prevented the enhancement of IL-1 activity induced by exogenous paf. In contrast, L-652,731 had little effect on MDP-induced IL-1 synthesis in the absence of exogenous paf. This may indicate that there are alternative mechanisms involved in the sequences of events leading to IL-1 production. It is also conceivable that the paf receptor antagonist is not able to compete or inhibit endogenous paf as well as it does for exogenous paf. Nevertheless, exogenous paf in association with a second signal, modulates IL-1 production from human monocytes in a positive manner. This may constitute another means through which paf can modulate inflammatory and immune reactions.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1990

Cooperation between platelets and neutrophils for paf-acether (platelet-activating factor) formation.

Association of platelets and neutrophils is frequently observed within thrombi or inflammatory sites. Interactions between these two cell populations have been reported for the production of several mediators of inflammation such as hydrogen peroxides or leukotrienes. Another potential mediator of thrombosis and inflammation is paf-acether, which is synthesized by activated platelets and neutrophils. Since platelets form and release large amounts of the paf-acether precursor lyso paf-acether, platelet and neutrophil cooperation for paf-acether biosynthesis was investigated. Purified human neutrophils (4 x 10(6)/ml) stimulated by opsonized zymosan (ZC, 1 mg/ml) formed 4.5 +/- 2.5 ng/ml paf-acether. Human washed platelets (3 x 10(8)/ml) stimulated with thrombin (1 IU/ml) formed 0.60 +/- 0.43 ng/ml paf-acether. Platelets and neutrophils, incubated together and both stimulated by their specific agonist, formed more than twice as much paf-acether as did platelets and neutrophils separately (10.90 +/- 4.25 ng/ml, n = 6, P less than .001). The formation of lyso paf-acether and the release of lysozyme and LDH were unchanged under the cooperation conditions. The formation of paf-acether almost doubled (10.24 +/- 3.81 ng/ml paf-acether vs. 5.30 +/- 2.23, P less than .05, n = 4) when ZC-stimulated neutrophils were incubated with supernatants from thrombin-stimulated platelets as well as with synthetic lyso paf-acether. Extracted and purified lyso paf-acether from thrombin-stimulated platelets led to an increase of biosynthesis of paf-acether by neutrophils (13.86 +/- 2.26 ng/ml paf-acether vs. 5.76 +/- 0.38, P less than .05, n = 3). These results indicate that a cooperation between platelets and neutrophils exists for paf-acether formation. The phenomenon depends on a platelet-derived soluble factor, possibly lyso paf-acether. This cell-to-cell interaction is of interest since paf-acether is formed by and acting on platelets and neutrophils and represents a molecular basis for potent amplification of inflammatory reactions.

Animals↗
PubMed1990

Monoclonal IgE-mediated cardiac hypersensitivity reactions in the guinea-pig.

Isolated heart preparations were prepared from guinea-pigs passively sensitized with mouse anti-DNP monoclonal IgE to study hemodynamic parameters and histamine release upon antigen challenge (DNP-BSA). In the best experimental conditions a triphasic response (increase, decrease, increase) in heart rate and in coronary flow occurred during 10 minutes after challenge. Coronary flow dramatically decreased (50%) at 2.5 min flanked by two periods of increase in flow and tachycardia (+ 55% of the basal heart rate). Contractile force decreased and remained at 80% of its initial value. Histamine is released within 2 minutes after antigen injection. After this period, the observed hemodynamic modifications seem to be due to other anaphylactic mediators such as prostaglandins, leukotrienes and most probably paf-acether.

Animals↗
PubMed1990

Production of paf-acether by human epidermal cells.

The production of the inflammatory mediator paf-acether (paf) from human epidermal cells was investigated in vitro. Human epidermal cells, freshly isolated from normal skin or in culture, were incubated in Tyrode's buffer containing 0.25% lipid-free bovine serum albumin in the presence of 2 microM calcium ionophore A23187, at 37 degrees C, for 1 to 60 min. Paf production slightly began at the first min of stimulation, was significant after 10 min, reached a maximum at 20 min (251 +/- 25 pg/l X 10(6) cells, mean +/- 1 SD), and decreased thereafter. About 50% of the paf amount produced by epidermal cells was recovered in supernatants. Addition of the non-acetylated paf precursor 1-O-octadecyl-sn-glycero-3-phosphocholine, i.e., lyso-paf, at 0.1 microM to epidermal cells during A23187-stimulation did not alter this production. In contrast, addition of acetyl-coenzyme A at 0.1 mM enhanced paf production by 5 times. The material produced by epidermal cells was identical to synthetic paf because: 1) the aggregation of aspirin-treated and ADP-insensitive washed rabbit platelets it induced was inhibited by BN 52021, an antagonist of the paf putative receptor; 2) the factor was inactivated by phospholipase A2 but was insensitive to lipase from Rhizopus arrhizus; 3) it exhibited the same retention time as synthetic paf during standard and reverse-phase (RP) high-pressure liquid chromatography (HPLC) elution. The paf precursors, i.e., lyso-paf and 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine, were also detected in epidermal cells, stimulated with A23187 or not. As determined by RP-HPLC analysis and confirmed by gas chromatography analysis, these precursors and the paf produced by epidermal cells exhibited more than 90% of a hexadecyl chain at the sn-1 position of the molecule. The present results demonstrate the synthesis and release of paf by normal human epidermal cells. Paf production within the epidermis might account for the development of cutaneous inflammation and the pathogenesis of many skin disorders.

Acetyl Coenzyme A↗
PubMed1990

Paf-acether synthesis by Helicobacter pylori.

Clinical studies suggest that Helicobacter pylori may play a role in the pathogenesis of gastroduodenal ulcers in man but direct evidence of mucosal injury by this microorganism is still lacking. Paf-acether (paf) causes a number of disorders including ischaemic bowel necrosis and gastroduodenal ulceration. Since paf is produced by Escherichia coli, we investigated whether it could be synthesised by H pylori. Five H pylori isolates were collected from antral biopsy specimens from patients with gastritis and duodenal ulcer and cultured with selective antibiotics. Colonies obtained from both blood agar and brucella broth medium were used. Paf was determined by platelet aggregation assay after ethanolic extraction and subsequent purification by high performance liquid chromatography. Paf was detected in H pylori in blood agar plates (680 (390) pg paf/1 x 10(6) organisms) but not in bacteria cultured on brucella broth medium. Supplementation of the latter medium with lyso paf and acetyl-CoA, two paf precursors present in high amounts in the mammalian intestine, induced paf production in three of five isolates. The platelet aggregating material extracted from H pylori exhibited biological and physiochemical characteristics identical to those of paf released from eukaryotic cells. These findings suggest that H pylori may add to the local production of paf in inflamed gastric mucosa.

Bacteriological Techniques↗
PubMed1989

Presence of paf-acether in human thymus.

Paf-acether (paf) is a phospholipid mediator of inflammation endowed with major immunoregulatory properties. The present study demonstrates that human thymus contains large amounts of paf, as well as paf precursors. In addition, isolated thymic cells produced paf under ionophore stimulation. Paf from thymus exhibited the same biological and physiochemical properties as synthetic paf. The purity and molecular structure of paf from thymus were further characterized by reverse-phase HPLC and gas chromatography with electron-capture detection. These findings may have important implications since thymus microenvironment is essential in the proper development of bone marrow progenitors committed to the T cell lineage into thymocytes capable of emigrating to the periphery as functional T lymphocytes.

Animals↗
PubMed1989

Paf-acether production by Escherichia coli.

Paf is a potent mediator of inflammatory diseases and septic shock. In previous studies we showed that paf can be released by prokaryotic cells such as E. coli. In this report we define the production and release of paf by E. coli cultured under different experimental conditions. When cultures were supplemented with lyso paf, a dramatic increase in paf production was observed. Most of the paf synthesized by bacteria was released in the supernatant. Of interest C16 lyso paf was 4-fold more efficient than its C18 counterpart. Using normal and reverse phase HPLC bacterial paf exhibited physico-chemical characteristics identical to those of synthetic paf. These results may indicate that the putative E. coli acetyltransferase recognizes differently C16 and C18 lyso paf. They also could be of importance considering the pathogenetic role of enterobacteria.

Chromatography, High Pressure Liquid↗
PubMed1989

Synthesis of paf-acether from exogenous precursors by the prokaryote Escherichia coli.

Paf-acether (paf) is a potent mediator of inflammatory diseases and septic shock. Using normal-phase HPLC, a paf-like activity was found in culture supernatants from E. coli. Prokaryotic paf exhibited the same biological and physico-chemical properties as eukaryotic cells and synthetic paf. Further, reverse-phase HPLC indicates that paf generated by bacteria is predominantly of the hexadecyl and octadecyl species. When cultures were supplemented with lyso-paf, a dramatic increase in paf production was observed. The purity and molecular structure of bacterial paf were further characterized by mass spectral analysis. These results could be of importance considering the pathogenetic role of enterobacteria. Further, it appears that the competence to form and release paf is an early phylogenetic development.

Animals↗