PubMed Health⌕ Search

Biomedical subjects

P Poubelle

Publications and source records attributed to P Poubelle.

At least 19 recordsLinked to original sources
PubMed1995

An interleukin 1 receptor antagonist blocks the IL-1-induced IL-6 paracrine production through a prostaglandin E2-related mechanism in multiple myeloma.

By analogy with the model of pristane-induced mouse plasmacytomas, we have wondered about the putative role of prostaglandin E2 (PGE2) in the human multiple myeloma (MM) cytokine network, involving interleukin 6 (IL-6) and interleukin 1 (IL-1) as essential myeloma cell growth factors and inducing cofactors respectively. We show that PGE2 is produced in short-term cultures of bone marrow cells of patients with MM, concomitantly with both IL-6 and IL-1. Indomethacin, a potent inhibitor of cyclo-oxygenase and of PGE2 synthesis, significantly inhibits IL-6 production (but not IL-1 production) by 35% to 90% depending on the different MM patients studied and concurrently to that of PGE2. Exogenous PGE2 reverses this inhibition or even stimulates IL-6 production. An IL-1 receptor antagonist (IL-1RA) also significantly inhibits PGE2, IL-6 production and myeloma cell growth. The inhibition of IL-6 production is reversed by adding exogenous PGE2. These results show that induction of IL-6 by IL-1 is related to PGE2 in the bone marrow of patients with MM. Inhibition of PGE2 synthesis (as obtained with indomethacin and the IL-1RA) might be helpful to inhibit myeloma cell proliferation by reducing IL-1-induced endogenous IL-6 production not only in vitro (as demonstrated here) but also in vivo.

Animals↗
PubMed1987

Carboxypeptidase N (kininase I) activity in blood and synovial fluid from patients with arthritis.

Carboxypeptidase N (CPN, kininase I) and kininase II (angiotensin converting enzyme) activities were measured simultaneously in blood plasma and synovial fluid in patients suffering from rheumatoid arthritis (RA), psoriatic arthritis (PA) and osteoarthritis (OA) and in the plasma of normal volunteers. CPN levels (defined as the rate of hydrolysis of furylacryloyl-Ala-Lys) in blood were modestly increased and correlated with erythrocyte sedimentation rate in RA and PA. Based on the hydrolysis of synthetic substrates, CPN activity was much higher than kininase II activity in synovial fluid (SF). SF kininase activities were always inferior to the blood levels in all patients and were correlated with the logarithm of SF leukocyte counts, an indicator of the intensity of inflammation. In addition, CPN and albumin levels in SF were highly correlated when expressed as a percent of the plasma concentrations. Biochemical properties of CPN in crude SF confirmed its similarity to blood CPN. Polymorphonuclear leukocytes derived from inflammatory SF did not release CPN. It is concluded that kininases diffuse from the blood into SF through increased vascular permeability and that CPN could be a major metabolic pathway for kinins in this form of exudate. CPN leads to the formation of des-Arg kinins, selective agonists of the B1 receptors for kinins.

Arthritis↗
PubMed1987

Fibronectin gene expression in polymorphonuclear leukocytes. Accumulation of mRNA in inflammatory cells.

Using a fibronectin cDNA probe, we have studied the accumulation of fibronectin mRNA in polymorphonuclear leukocytes (PMN) in response to inflammation. Nonactivated PMN from human peripheral blood were used as a source of noninflammatory cells and PMN from inflamed knee joints of patients with chronic inflammatory joint disorders (rheumatoid and psoriatic arthritis) were used as a source of inflammatory cells. By dot blot and Northern hybridization analysis, we have found the presence of fibronectin mRNA in these cells. Its size was estimated at approximately equal to 8.7-8.8 kilobases. When noninflammatory PMN were compared to inflammatory PMN in terms of fibronectin mRNA accumulation, a marked increase was found in inflammatory cells (2- to 12.7-fold stimulation). It was also observed that the increased mRNA levels in inflammatory PMN lead to increased synthesis of the protein. These findings establish that PMN are part of the fibronectin-producing cells and that the level of mRNA in these cells is influenced by the inflammatory process.

Arthritis↗
PubMed1987

Conversion of arachidonic acid into 12-oxo derivatives in human platelets. A pathway possibly involving the heme-catalysed transformation of 12-hydroperoxy-eicosatetraenoic acid.

Analysis of arachidonic acid metabolites in human platelets by reverse-phase HPLC with radioactivity and UV detection revealed, besides Thromboxane B2 (TXB2), 12-hydroxy-heptadecatrienoic acid (HHT) and 12-hydroxy-eicosatetraenoic acid (12-HETE) previously described, two peaks of unidentified material absorbing at 280 nm. This material was purified by straight-phase HPLC and characterized by UV spectroscopy and gas chromatography-mass spectrometry. Three carbonyl compounds were identified: 12-keto-5,8,10,14-eicosatetraenoic acid and two geometric isomers of 12-oxo-5,8,10-dodecatrienoic acid. In a 5 min incubation at 37 degrees C in the presence of 9 microM arachidonic acid, the yield was of 0.5 to 1% of added arachidonic acid for the ketonic compound and of 4 to 7% for the sum of the two isomeric fatty acid aldehydes in comparison to 10 to 13% and 25 to 28% for TXB2 and 12-HETE, respectively. Because the three compounds carry a carbonyl group at position 12, their relationship with the 12-lipoxygenase pathway was investigated. It was found that the three compounds were formed when 12-hydroperoxy-eicosatetraenoic acid (12-HPETE) was incubated with intact or heat denaturated platelets or hemoproteins, strongly suggesting that these carbonyl compounds are products of a heme-catalysed transformation of 12-HPETE.

Arachidonic Acid↗
PubMed1987

[Effect of SIN-1 on the synthesis of leukotrienes in human polymorphonuclear cells].

Leukotriene (LT) synthesis triggered with ionophore A23187 or inflammatory stimuli (PAF, fMLP) in human polymorphonuclear leukocytes (PMNL) was markedly decreased by SIN-1, an active metabolite of molsidomine. This inhibition occurred in the absence or in the presence of exogenous arachidonic acid (AA). These results suggest that SIN-1 inhibited both the release of AA from membrane phospholipids and the 5-lipoxygenase activity in human PMNL. Molsidomine was without any effect on LT formation.

Arachidonic Acids↗
PubMed1987

Protein biosynthetic activity of polymorphonuclear leukocytes in inflammatory arthropathies. Increased synthesis and release of fibronectin.

We have investigated protein synthesis and release by polymorphonuclear leukocytes (PMN) to compare the protein biosynthetic activity of peripheral blood PMN and inflammatory synovial fluid (SF) PMN from patients with inflammatory arthropathies. We analyzed and compared the protein profiles produced by these cells, using patient matched peripheral blood and SF PMN as well as peripheral blood PMN from normals. Twenty-five patients with either rheumatoid arthritis, psoriatic arthritis or gout were studied. Fluorographs of SDS-polyacrylamide slab gels, performed using cell supernatants from metabolically labelled cells, revealed an increased release of de novo synthesized proteins by inflammatory SF PMN compared to peripheral blood PMN. Under reducing conditions, 4 clearly distinguishable high molecular mass products were observed (Mr 230,000, 185,000, 170,000 and 95,000). Two of the protein bands were found to be gelatin binding (Mr 230,000 and Mr 95,000). By Western blot, the Mr 230,000 protein was found to be fibronectin and the Mr 95,000 protein was shown to be identical to a recently described gelatinase. Thus, the activation of PMN in inflammation is accompanied by an increased release of a number of de novo synthesized proteins, including fibronectin. Our studies directly pertain to the in vivo inflammatory process since the PMN were not activated artificially in vitro.

Arthritis↗
PubMed1985

Intraperitoneal injection of zymosan in mice induces pain, inflammation and the synthesis of peptidoleukotrienes and prostaglandin E2.

Intraperitoneal injection of zymosan in mice induced rapid extravasation and accumulation of plasma protein in the peritoneal cavity. Neutrophils began to appear in the peritoneal cavity after a lag period of approximately 3 hours. The injected mice exhibited a pain response (writhing) during the first 30 minutes after injection, but writhing ceased before protein or cell accumulation had reached maximum levels. The injection of zymosan induced synthesis of PGE2 (measured by RIA) which reached maximum levels at 30 minutes, then declined slowly. Peptido-leukotriene levels (detected by bioassay, RIA and HPLC) increased rapidly after injection, reached a peak within an hour of injection and declined to undetectable levels within 4 hours. The early peptido-LT was predominantly LTC4, while later, LTE4 was the major component. LTD4 levels remained low throughout and no LTB4 was detected at any time. Indomethacin treatment elevated levels of peptido-LTs, reduced PGE2 levels and inhibited writhing. Phenidone reduced peptido-LT levels. In vitro studies demonstrated that zymosan stimulates LTC4 synthesis by peritoneal cells whereas LTE4, LTD4, LTB4 or monoHETES were not detectable (using HPLC methods). The source of enzymes responsible for the in vivo metabolism of LTC4 to LTD4 and LTE4 could not be identified.

Animals↗
PubMed1985

Production of mononuclear cell factor by mononuclear phagocytes from rheumatoid synovial fluid.

Collagenase-and PGE1-stimulating activities (mononuclear cell factor or MCF) have been found in culture supernatants from synovial fluid macrophages (SF-M phi) of patients wih rheumatoid arthritis. The apparent molecular weight of the MCF activity present in SF-M phi supernatants was between 15-20,000 daltons, which is similar to interleukin I. All the SF-M phi supernatants from patients tested showed the MCF activity. Our study presents evidence for MCF production by monocyte-macrophages at the local site of the lesion.

Adult↗
PubMed1984

Arachidonic acid metabolism among human mononuclear leukocytes. Lipoxygenase-related pathways.

Human peripheral blood mononuclear cells were isolated and assessed for the presence of contaminating polymorphonuclear leukocytes and platelets. Incubations of these cell isolates were performed in the presence or absence of the calcium ionophore A23187 and/or 1-14C-labeled or unlabeled arachidonic acid. Using reverse phase high pressure liquid chromatography with simultaneous monitoring of ultraviolet light absorption at 229 and 280 nm and, where appropriate, of radioactivity, our studies reveal that human peripheral blood mononuclear cells generate leukotrienes C4 and B4 (LTC4 and LTB4) and 5-hydroxyeicosatetraenoic acid (5-HETE) following stimulation with A23187. The ratio of LTC4 to LTB4 was approximately 10-fold greater among the mononuclear cells than among similar incubations of polymorphonuclear leukocytes. Furthermore, the mononuclear cells failed to metabolize LTB4 into the omega-hydroxy or omega-carboxy derivatives that were always present in, and very characteristic of incubations of polymorphonuclear leukocytes. Depletion of monocytes from the mononuclear cells by double adherence resulted in virtual loss of the generation of 5-lipoxygenase-derived products by the remaining nonadherent cells, supporting the conclusion that the monocytes and not the lymphocytes were the source of LTC4, LTB4, and 5-HETE. The presence of both 12-HETE and the cyclooxygenase-derived 12-hydroxyheptadecatrienoic acid correlated with the degree of platelet contamination, suggesting that the platelets account for the presence of these compounds.

Arachidonic Acids↗
PubMed1983

Ultrastructural and crystallographic study of calcifications from a patient with CREST syndrome.

An ultrastructural and crystallographic study was done on calcium deposits obtained from a patient with the CREST syndrome. Optical microscopy showed that large calcific cutaneous deposits seemed to have developed in a dense connective tissue without any inflammatory reaction. The oldest lesions contained heterotopic bone. Electron microscopy showed that calcium deposit, in the slightly mineralized fibers, was located at the center of the elastic fibers. The calcifications were surgically removed and studies were performed on the rough products and, after heating, using x-ray crystallography, differential thermal analysis and quantitative chemical analysis. Our results showed that this cutaneous calcification is a B type carbonated apatite.

Aged↗
PubMed1982

Mononuclear phagocytes, prostanoids and rheumatoid arthritis.

We describe a new, simple procedure for obtaining and studying mononuclear phagocytes from inflammatory synovial fluid. The viability and functional characteristics of these macrophages have been carefully checked. This technique has been used to evaluate the macrophagic synthesis of prostaglandins in 16 patients with evolutive rheumatoid arthritis. Significant amounts of prostaglandins, mainly PGE2 and TxB2, are released and increased after zymosan administration. The three tested prostaglandins (PGE2, PGF2 alpha and TxB2) responded in a similar manner. The in vitro PG biosynthesis and the number of harvested adherent cells are negatively correlated with the synovial fluid volume but positively correlated with the disease activity. In fact, we found an heterogeneity among the analyzed macrophages; these can be divided into two populations with marked differences in their PG biosynthesis. The one with the highest synthesis corresponded to the more severe disease.

Arthritis, Rheumatoid↗
PubMed1982

[Mononucleated phagocytes from rheumatoid synovial fluid. Synthesis of prostanoids and first pharmacological applications].

An original and easily reproducible technique for isolating and culturating mononucleated phagocytes from rheumatoid synovial fluid was used by the authors to study the synthesis of PGE2, PGF alpha 2 and TxB2 by macrophages taken from 16 patients with rheumatoid arthritis. The functional importance of these macrophages was evaluated by comparing their ratios of prostaglandin synthesis. PGE2 and TxB2 are released in large quantities and are increased after stimulation with zymosan. Two distinct cell populations having different biochemical characteristics were identified from these macrophages based on their capacity to synthesize prostaglandins. Prostaglandin synthesis was correlated with the clinical progression of rheumatoid arthritic disease as evaluated by Lee's index and the time required to loosen up morning joint stiffness in these patients. No correlation was found between prostaglandin synthesis and the quantity of synovial fluid in the affected joint. The first results of a pharmacological study evaluating the activity of non steroid anti-inflammatory drugs using this experimental model are presented here. The addition of indomethacin to culture medium produces dose-dependent inhibition of prostaglandin synthesis.

Adult↗
PubMed1982

Plasma lipoperoxides and aging. Critical assessment of the thiobarbituric acid method for the measurement of lipoperoxides and malondialdehyde.

Thiobarbituric acid reactive products were measured in plasma of 66 normal subjects ranging from 19 to 92 years of age. A significant correlation (r = 0.54, p less than 10(-6) was formed between the level of these metabolites and the age of the subjects. As a matter of fact this method analyzes two kinds of substances from two different origins, free malondialdehyde or lipid peroxides. These two fractions were identified by extracting lipids using Folch's method and leaving all free malondialdehyde in the plasma (95.6 +/- 11.8% recovery for a known amount added to the plasma). Plasma analysis prior to and after extraction showed that thiobarbituric acid reactive products were lipid peroxides for 74.8 +/- 4.3%, the remainder being free malondialdehyde. The origin of these two fractions is discussed.

Adult↗
PubMed1980

[Technic for isolation and culture of macrophages from human synovial fluid].

Macrophages from synovial fluid were obtained by joint puncture of patients with rheumatoid arthritis or non-rheumatoid exudative arthropathies. This fluid was subsequently centrifuged and the resulting cell pellet was recovered and distributed for in vitro culture (Falcon Petri dishes: 60 x 15 or 35 x 10). Cells were washed after 4 hours in culture to eliminate non-macrophagic cells. A second cell wash was effected 24 hours later to eliminate non-adherent cells. The culture medium employed was fetal calf serum MMP 119 (Gibco). The macrophagic nature of the cultured cells was ascertained by non specific esterase determinations (Burstone method) and estimation of the phagocytic index (using zymosan). This technique permits the conservation of viable monocytes in culture thus facilitating investigation of their metabolic activity (for example: prostaglandins, prostanoids or fatty acids) and the effects of anti-inflammatory agents.

Arthritis, Rheumatoid↗
PubMed1980

PGE2, PGF2 alpha, and TXB2 biosynthesis by human rheumatoid synovia.

Prostaglandins (PG) are currently suspected to be involved in human rheumatoid arthritis (RA). We have studied the PG [PGE2, PGF2 alpha, and Thromboxane B2 (TXB2)] biosynthesis capacity of normal (from amputations) and pathologic (osteoarthritis (OA) and RA) synovia. The measurement is done on the whole homogenate and microsomal fraction after 40 min incubation, without exogenous arachidonic acid (AA) or with a saturating concentration (25 micrograms/ml) of this compound, using a radioimmunoassay method. There is a considerable increase in PGE2 and PGF2 alpha production by the rheumatoid synovia and more PGE2 and PGF2 alpha are formed. This production is more marked for homogenates than microsomal fraction. The OA group is not homogeneous and does not differ significantly either from normals or from RA. The addition of AA considerably increases the biosynthesis of PG in both normal and pathologic tissue. For TXB2, the first results (four synovia) show no or a small biosynthesis in RA as well as in normals. Nevertheless, the levels before incubation seem higher in RA than in normal tissue.

Arachidonic Acids↗
PubMed1979

[Prostatic osteosis. Retrospective study of 110 cases treated with high-dose estrogens].

On the basis of 110 prostatic osteoses that were histologically proven, constantly painful and demonstrated by X-ray, treated by early estrogenotherapy using very high doses, backed up by a high-dose maintenance estrogenotherapy, the authors study the clinical, radiological, histological and biological profile of this metastatic cancer, as well as the response to treatment. The median actuarial survival time of the patients studied is 18.5 months. No statistically significant prognostic correlation was found. Only patients who are clinically estrogen-sensitive, are suffering from bone metastases without a combined visceral conditions, and have a normal initial rate of alcaline phosphates, tend to have a better prognosis (median actuarial survival 31 months versus 18.5 months for the overall population).

Adult↗