Search PubMed⌕ Search

Biomedical subjects

M Pascal

Publications and source records attributed to M Pascal.

14 recordsLinked to original sources
PubMed1992

O-acylated heparin derivatives with low anticoagulant activity decrease proliferation and increase alpha-smooth muscle actin expression in cultured arterial smooth muscle cells.

Selectively O-acylated derivatives of various glycosaminoglycans were prepared and tested in vitro for their anticoagulant activity and their antiproliferative effect on rat and rabbit smooth muscle cells. When O-acylation (butyrylation or hexanoylation) had been performed on periodate-depolymerized heparin fragments having very low anticoagulant activity, the antiproliferative potency was markedly increased (IC50 = 2 and 1 micrograms/ml respectively, versus 31 micrograms/ml for starting compound) without an increase in anticoagulant activity. The antiproliferative activity was related to the degree of acylation. The O-acylated derivatives of heparin fragments were also very active in reversing the de-differentiation of smooth muscle cell in culture, as estimated by the increase in the expression of alpha-smooth muscle actin and alpha-smooth muscle actin mRNA.

Actins↗
PubMed1991

Thymectomy at weaning. An accelerated aging model for the mouse immune system.

Mouse thymectomy at weaning induces a long lasting immunodepression which can be measured by in vivo and in vitro experiments. Lymphocyte proliferation and IL2 production in response to a T cell mitogen are greatly diminished during the whole life of the animals, on the contrary B cell proliferation in the presence of lipopolysaccharide is not modified. The lack of effect of surgery on the in vitro T cytotoxic activity compared to the total abolition of in vivo graft versus host reaction shows that these two phenomena are under the control of different immunocompetent cell subsets. Thymectomy induces a stabilization of natural killer cell activity, while during normal aging, this parameter decreases regularly. Surprisingly, the thy 1+ cell level is normal 8-10 months after thymectomy compared to sham operated animals showing that phenotypically normal cells can be dysfunctional. Macrophage activity is not modified either by aging or by thymectomy. So, thymectomized mice can be used after less than 1 year to study immunopharmacology of aging.

Aging↗
PubMed1991

Implications of prostaglandin E2 synthesis and phospholipase C activation in potentiation of T-cell proliferation by LF 1695.

Murine spleen cells, T-enriched by nylon wool filtration, proliferate in the presence of a protein kinase C stimulator and a calcium ionophore. Using this cell proliferation system, we show that LF 1695 can potentiate phorbol myristate acetate (PMA) action in the presence of A 23187. This potentiation can be due to PGE2 inhibition since it is found that lipopolysaccharide (LPS) or A 23187 induced PGE2 release from spleen cells is inhibited by LF 1695. Indomethacin and LF 1695 gave similar stimulation of spleen cell proliferation, and exogeneously added PGE2 inhibits this phenomenon. Considering two of the main early components of intracellular signal transduction, LF 1695 induces IP3 release and calcium mobilization. However, the compound is not mitogenic per se. These results show that LF 1695 behaves only as a costimulant for T-cell proliferation.

Animals↗
PubMed1991

A new immunomodulator, LF 1695--II. Effects on allogenic and antigenic responses.

LF 1695, a chemically defined immunomodulator has been shown to induce in vitro T-cell differentiation and to potentiate mitogenic proliferation. The effects of LF 1695 on antigenic and allogenic responses were studied in vitro and lymphocyte proliferation was estimated by 3H-thymidine uptake for 5 and 6 days, respectively. Human peripheral blood lymphocytes (PBL) from tuberculin sensitive donors were significantly stimulated by purified protein derivative (PPD) in the presence of LF 1695. Optimal lymphocyte proliferation with PPD was obtained at 0.5 micrograms/ml LF 1695. The ability of LF 1695 to enhance proliferation of PBL in an allogenic reaction was also examined. LF 1695 (0.2 micrograms/ml) enhanced the proliferation of PBL from two individuals with different HLA DR loci in the bilateral mixed lymphocyte reaction (MLR). Moreover, LF 1695 was tested in vivo in the experimental graft vs host reaction (GvHR) in mice. CBA, H2k mice receiving a lethal dose of irradiation were injected with spleen cells from LF 1695-treated or untreated C57 Bl/6, H2b mice via different routes. CBA mice were found to have a spleen weight x 1000/body ratio up to 1.5 when injected with cells from untreated C57 Bl/6 mice. Mice treated intraperitoneally with LF 1695 at 2.5 or 5 mg/kg/day showed an increase of GvHR intensity with splenic index of 1.71 and 1.80, respectively. When the animals were treated continuously through drinking water containing LF 1695 (4 mg/kg, 10 mg/kg or 100 mg/kg), these ratios were: 1.82, 1.10 and 1.37, respectively. Finally, LF 1695 enhanced GvHR significantly when used at low doses, while high doses induced a decrease of GvHR intensity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

(Benzoylphenyl)piperidines: a new class of immunomodulators.

A series of (benzoylphenyl)piperidines has been synthesized and evaluated for activity as immunomodulators. Several of these compounds show good activity in primary screening on the basis of the lymphocytes mitogenic response to Con A, PHA, and PWM. A chloro group in position 4 of the benzoyl moiety as well as an amino group (or a carbamate derivative) para to the piperidine nucleus seems to be essential for activity. The depicted compounds may be considered as the first examples of a new series of immunomodulators.

Adjuvants, Immunologic↗
PubMed1991

Discontinuation of lithium treatment in remitted bipolar patients: relationship between clinical outcome and changes in sleep-wake cycles.

In this preliminary report, we describe four patients in whom long-term lithium therapy was discontinued, combined with actigraphic monitoring to assess changes in motor activity and the sleep-wake cycle. Two patients experienced rapid relapse of manic symptomatology, while two remained stable throughout a 1-year follow-up. Actigraphic monitoring revealed disintegration of the sleep-wake cycle and increased motor activity in the relapsed patients only. It is suggested that actigraphic recordings can be used to monitor lithium discontinuation.

Ambulatory Care↗
PubMed1989

Stimulation of 12-HETE production in human platelets by an immunomodulator, LF 1695. Evidence for activation of arachidonate liberation coupled to cyclo-oxygenase inhibition.

Upon incubation with human platelets previously labelled with [14C]arachidonic acid, a new immunomodulator, LF 1695, induced the accumulation of [14C]-12-(S)-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE). Although the time course of [14C]HETE accumulation was identical with 60 microM LF 1695 and calcium ionophore A23187, the latter compound also promoted the formation of 14C-labelled thromboxane B2 and 12-(S)-hydroxy-5,8,10-heptadecatrienoic acid (HHT), whereas 12-HETE was the only arachidonic acid metabolite generated under the action of LF 1695, suggesting that the drug inhibited cyclo-oxygenase. This was further confirmed by the fact that LF 1695 inhibited the second wave of platelet aggregation induced by ADP as well as arachidonic acid effects. Cell lipid analysis revealed that arachidonic acid was liberated from both triacylglycerol and phosphatidylcholine. The effect was observed in the concentration range 15-90 microM, with a half-maximal effect at 30 microM for HETE production, 15 microM for triacylglycerol hydrolysis and 45 microM for phosphatidylcholine deacylation. Incubation of platelets with [14C]arachidonic acid in the presence of 60 microM LF 1695 resulted in a strong inhibition of arachidonic acid incorporation into the various cell lipids, indicating that arachidonic acid mobilization might be due to inhibition of reacylation processes. It is concluded that LF 1695 displays an original and complex effect on platelet lipid metabolism, resulting in the specific generation of lipoxygenase metabolites.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1979

DNA polymerase-alpha from regenerating rat liver. Catalytic properties of the highly purified enzyme.

DNA polymerase-alpha from the cytosol of regenerating rat liver has been highly purified by a procedure which includes affinity chromatography. The purified enzyme sediments at 7.4 S in high ionic strength and at 9--10 S in low ionic strength, i.e. under in vitro polymerization conditions. This enzyme has all the properties of the other mammalian DNA polymerases-alpha: sensitivity to sulfhydryl-blocking agents, to heparin, and to the level of salt in the assay, neutral pH optimum, use of ribonucleotide-initiated DNA templates, and inability to copy the ribostrand of hybrids. After chromatography on denatured DNA-cellulose, the alpha-polymerase is completely devoid of exo- and endonuclease activities. Template competition experiments indicate that the binding of the enzyme to the template can be distinguished from the polymerization itself and that the in vitro synthesis catalyzed by this alpha-polymerase is not distributive in a classical sense. These facts are discussed.

Animals↗
PubMed1978

Calf-spleen nicotinamide-adenine dinucleotide glycohydrolase. Properties of the active site.

The interaction between the nicotinamide adenine dinucleotide binding domain of calf spleen NAD glycohydrolase and its ligands has been studied. The use of competitive inhibitors, structurally related to different portions of the NAD molecule (i.e. adenosine and nicotinamide moieties), revealed the considerable importance of the binding between the pyrophosphate linkage and probably an arginyl residue of the active site. This interaction allows the positioning of the substrate in a conformation which permits catalysis to occur. The binding between the 2'-hydroxyl of the adenosine moiety and a residue of the active site, which exists in NAD-linked dehydrogenases, is probably missing in the calf spleen NAD glycohydrolase, based on the inhibition by salicylates, 2'-deoxyadenosine 5'-monophosphate and the hydrolysis of the 2'-deoxyadenosine analogue of NAD. The NAD glycohydrolase could be completely inactivated by 2,3-butanedione, an arginyl-modifying reagent. The reaction followed pseudo-first-order kinetics and the modification was found to be reversible. Woodward's reagent K, a reagent for carboxyl residues, partially inactivated the enzyme, which resulted in a change of the NAD glycohydrolase kinetic parameters Km and V. The inactivation rate was complicated by a parallel decomposition of the reagent.

Adenine Nucleotides↗
PubMed1977

[Comparative study of the formation of glycogen and trehalose during starvation in the Lepidoptera Bombyx mori L].

Glycogen reserves are entirely consumed during total starvation of Bombyx mori L. larvae. While the storage of glycogen is lowering and the dietary supply of carbohydrates stopped, the amount of trehalose also decreases but less rapidly than this of glycogen. Relative homeostasis is maintained but only for the ten first hours of inanition. Quantitative evaluation of blood trehalose, which is preformed more rapidly than glycogen analysis, might be used as an efficient test to characterized some physiopathological states.

Animals↗
PubMedDate not supplied

[Complementary procedures to the Sjoqvist operation in cancerous cervico-facial pain].

The trigeminal spinal tractotomy of Sjoqvist can be enlarged and give a very good result on cancer pain of face and throat. When pain is also cervical, it is usefull to associate with the Sjoqvist operation two important procedures: 1 degree--Instead of a simple posterior cervical radicotomy it seems best to practise a selective posterior radicellotomy. This technic has the advantage to preserve the sensory proprioceptive capacity of the superior limb, while being perform even until C6 and C7 roots. Also in case of recurrence of cervico brachial pain, it remains easy to apply a posterior spinal stimulation. 2--The spinal nerve has not only a motor function but also a sensory one. The sensory fibers travelling through small anastomosis between "LARUELLE Ganglion" and cervical roots must be separated to obtain a more complete analgesia.

Facial Neuralgia↗