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D Denis

Publications and source records attributed to D Denis.

At least 37 records · Page 2Linked to original sources
PubMed1999

Phosphodiesterase 4-dependent regulation of cyclic AMP levels and leukotriene B4 biosynthesis in human polymorphonuclear leukocytes.

Several selective phosphodiesterase 4 inhibitors were found to be potent inhibitors of the N-formyl-Met-Leu-Phe (fMLP)-induced leukotriene B4 biosynthesis by human polymorphonuclear leukocytes with IC50s in the nanomolar range (0.09-26 nM). The rank order of potency was 6-(4-pyridylmethyl)-8-(3-nitrophenyl)quinoline (RS-14203) > 3-benzyl-5-phenyl-3H-imidazo[4,5-c][1,8]naphthyridin-4(5H)-one (KF18280) > 8-aza-1-(3-nitrophenyl)-3-(4-pyridylmethyl)-2,4-quinazoline dione (RS-25344) > 3-cyclo-pentyloxy-N-[3,5-dichloro-4-pyridyl]-4-methoxybenzamide (RP-73401) > R-rolipram > R-4-[2-(3-cyclopentyloxy-4-methoxyphenyl)-2-phenylethyl] pyridine (CDP840)> S-rolipram. Isoproterenol (IC50 = 350 nM) and prostaglandin E2 (IC50 = 59 nM) also suppressed leukotriene B4 biosynthesis. Inhibitors of the phosphodiesterase 1 (8-methoxymethyl-1-methyl-3-(2-methylpropyl)xanthine (8-MeOMe-IBMX)), phosphodiesterase 2 (erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA)), phosphodiesterase 3 (quazinone and milrinone) and phosphodiesterase 5 (zaprinast and dipyridamole) had no inhibitory effects on the fMLP-induced leukotriene B4 biosynthesis (IC50s > 20 microM). All phosphodiesterase 4 inhibitors caused an accumulation of cellular cyclic AMP to 140-185% over the basal level of fMLP-treated control cells, comparable to that observed with high concentrations of isoproterenol and prostaglandin E2. In contrast, the complete inhibition of leukotriene B4 production by 5-lipoxygenase and 5-lipoxygenase-activating protein (FLAP) inhibitors had no effect on cyclic AMP levels. Phosphodiesterase 1, 2, 3 and 5 inhibitors had little effect on the level of cellular cyclic AMP (89-126% of the basal cyclic AMP level). Dose-dependencies for R-rolipram, RS-14203 and CDP840 indicated that the maximal accumulation of cyclic AMP occurred at concentrations of phosphodiesterase 4 inhibitors higher than those required for the inhibition of leukotriene B4 production. The presence of a mixture of 8-MeOMe-IBMX, EHNA, milrinone and zaprinast to inhibit phosphodiesterase 1, 2, 3 and 5 had little effect on the dose-dependence of R-rolipram for the inhibition of leukotriene B4 biosynthesis or cyclic AMP accumulation. These data demonstrate that selective phosphodiesterase 4 inhibitors can inhibit the fMLP-induced leukotriene B4 biosynthesis in human polymorphonuclear leukocytes with a potency similar or greater than that of potent 5-lipoxygenase or FLAP inhibitors. This inhibition is accompanied by small variations in the levels of cellular cyclic AMP and appears to proceed independently of the other phosphodiesterases.

Cyclic AMP↗
PubMed1999

Distribution and regulation of cyclooxygenase-2 in carrageenan-induced inflammation.

1 We characterized the regulation of cyclooxygenase-2 (COX-2) at the mRNA, protein and mediator level in two rat models of acute inflammation, carrageenan-induced paw oedema and mechanical hyperalgesia. 2 Carrageenan was injected in the hind paw of rat at low (paw oedema) and high doses (hyperalgesia). COX-2 and prostaglandin E2 (PGE2) levels were measured by RT-PCR and immunological assays. We also determined the distribution of COX-2 by immunohistochemistry. 3 The injection of carrageenan produced a significant and parallel induction of both COX-2 and PGE2. This induction was significantly higher in hyperalgesia than in paw oedema. This was probably due to the 9 fold higher concentration of carrageenan used to provoke hyperalgesia. 4 Immunohistochemical examination showed COX-2 immunoreactivity in the epidermis, skeletal muscle and inflammatory cells of rats experiencing hyperalgesia. In paw oedema however, only the epidermis showed positive COX-2 immunoreactivity. 5 Pretreatment with indomethacin completely abolished the induction of COX-2 in paw oedema but not in hyperalgesia. 6 These results suggest that multiple mechanisms regulate COX-2 induction especially in the more severe model. In carrageenan-induced paw oedema, prostanoid production have been linked through the expression of the COX-2 gene which suggest the presence of a positive feedback loop mechanism.

Animals↗
PubMed1998

Rhabdomyolysis in European viper bite.

The case of a child who presented with severe rhabdomyolysis associated with renal failure after a viper bite is reported. Rhabdomyolysis is a serious complication resulting from systemic envenomation and is uncommon after viper bites in Europe. It may be due to oedema, myotoxic agents and haemorrhagic factors and may be responsible for two types of potentially fatal complications, i.e. acute renal failure and hyperkalaemia. The present case highlights the need to investigate routinely for rhabdomyolysis after viper bites. Antivenom therapy is recommended as soon as signs of envenomation are present, without waiting for the onset of complications.

Animals↗
PubMed1998

Treatment of common ocular allergic disorders; a comparison of lodoxamide and NAAGA.

BACKGROUND/AIMS: Lodoxamide tromethamine and N-acetyl-aspartyl glutamic acid (NAAGA) are mast cell stabilisers, both of which have been shown to be effective in the treatment of allergic conjunctivitis. The aim of this study was to compare the two compounds in patients with common ocular allergic disorders. METHODS: 73 patients participated in a double masked, randomised multicentre study. Diagnoses were chronic allergic conjunctivitis, vernal conjunctivitis, seasonal and atopic conjunctivitis. 36 patients were treated with lodoxamide 0.1% and 37 with NAAGA 4.9%, the drops being instilled four times daily for up to 56 days. RESULTS: The overall opinion of the physicians and the patients was in favour of lodoxamide at day 10 of the study. At this time, 86% of lodoxamide treated and 49% of NAAGA treated patients considered they had improved. The patients' opinion favoured lodoxamide at day 28 and both physicians' and patients' evaluations were in favour of lodoxamide at day 42. Evaluation of signs and symptoms indicated superiority of lodoxamide at days 42 and 56. Both treatments were well tolerated. CONCLUSION: While both lodoxamide and NAAGA treatments are associated with clinical improvements in patients with allergic conjunctivitis, lodoxamide may have an earlier onset of action.

Adolescent↗
PubMed1998

[Brown syndrome: current status].

PURPOSE: Brown's syndrome is a form of anatomical strabismus, or retraction syndrome. It is defined by active and passive limitation of upward gaze in adduction in the field of action of the inferior oblique muscle. The etiology of Brown's syndrome remains unknown. The defect lies at the level of the superior oblique's tendonis trajectory via the trochlea. We studied the frequency of clinical signs and results after surgery in patients presenting congenital Brown's syndrome. PATIENTS AND METHODS: Our study involved 18 children. They all underwent complete ophthalmological examination with orthoptic testing, pre and postoperatively. RESULTS: Neither sidedness nor predominance of sex was noted. Compensatory head posture was noted in 7 of 18 cases. Limitation of upward gaze in adduction was a constant finding, with a positive duction test. Eleven cases underwent superior oblique recession. Results of surgery were satisfactory, with resolution of compensatory head posture in over 80% of cases. CONCLUSION: The etiology of congenital Brown's syndrome remains unknown. The different surgical techniques give inconstant results. Operative indication is decided only when in the presence of well defined clinical manifestations: CHP, deviation in primary position with alteration of binocular vision.

Child↗
PubMed1998

A biometric study of the eye, orbit, and face in 205 normal human fetuses.

PURPOSE: To develop models for assessing the differential growth of the fetal face along its horizontal and vertical axes, as well as of the orbit and the eye. METHODS: Normal human fetuses (n = 205), whose gestational ages ranged from 15.5 to 41 weeks of amenorrhea, were examined. Orbitofacial parameters were as follows: outer canthal distance, inner canthal distance, palpebral fissure length, and oropalpebral distance. Ocular parameters were corneal diameter and axial length. Correlations were tested among all parameters. Linear and polynomial regression analyses of gestational age and the orbitofacial and ocular parameters were used to develop models of growth. Differential patterns of growth in the face were investigated. RESULTS: The best correlation was found between palpebral fissure length and oropalpebral distance. The increase of each of the parameters studied could be accurately described by a linear model. Sex had no detectable effect on these parameters. Compared with the skull, the face had a more rapid growth along the vertical axis. The palpebral fissure developed more rapidly than the eye. CONCLUSIONS: The parameters that were studied in the fetal face, orbit, and eye follow a roughly linear growth curve.

Anthropometry↗
PubMed1997

Characterization of autocrine inducible prostaglandin H synthase-2 (PGHS-2) in human osteosarcoma cells.

The human osteosarcoma 143.98.2 cell line was found to express high levels of prostaglandin synthase-2 (PGHS-2) without detectable levels of prostaglandin synthase-1 (PGHS-1) as measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunoblot analysis. Maximal levels of PGHS-2 induction were attained when the cells were grown beyond confluence. The osteosarcoma cells also secrete IL-1 alpha, IL-1 beta and TNF alpha in the culture medium. PGHS-2 expression was inducible by the exogenous addition of these cytokines as well as conditioned media from auto-induced cultures and inhibitable by treatment with dexamethasone. In contrast, undifferentiated U937 cells selectively express PGHS-1 as analyzed by RT-PCR and Western blotting. The effects of non-steroidal anti-inflammatory drugs (NSAIDs) on the cellular PGE2 production mediated by each isoform of human PGHS were determined using osteosarcoma and undifferentiated U937 cells. When cells were preincubated with inhibitors to allow time-dependent inhibition prior to arachidonic acid stimulation, NS-398, CGP 28238, L-745,337, SC-58125 all behaved as potent (IC50 = 1-30 nM) and selective inhibitors of PGHS-2, in contrast to indomethacin, flurbiprofen or diclofenac which are potent inhibitors of enzymes. DuP-697 and sulindac sulfide were also potent inhibitors of PGHS-2 but both compounds inhibited cellular PGHS-1 activity at higher doses (IC50 = 0.2-0.4 microM). Time-dependent inhibition of PGE2 production in osteosarcoma cells was observed for indomethacin, diclofenac and etodolac. The synthesis of PGE2 by U937 cells was strongly dependent on exogenous arachidonic acid (100-fold stimulation) whereas confluent osteosarcoma cells also produced PGE2 without exogenous stimulus (7-fold stimulation by arachidonic acid). Osteosarcoma cells grown beyond confluence released more PGE2 from endogenous substrate than arachidonic acid stimulated undifferentiated U937 cells. These results indicate that osteosarcoma cells selectively express PGHS-2 with an autocrine regulation and effective utilization of endogenous arachidonic acid for PGE2 synthesis.

Arachidonic Acid↗
PubMed1997

[Psychiatric disorders after political imprisonment in the Soviet occupation zone and in the GDR from 1945-1972].

In an exploratory study, 54 persons, were examined who were imprisoned--for at least six months--for political reasons first in the Soviet Occupation Zone and/or later in the German Democratic Republic (East Germany) between 1945 and 1972. Conditions of imprisonment included means that may be classified as psychological torture. Biographical data, experiences of imprisonment, factors helpful for coping, and influence of imprisonment on the persons' life were investigated in a semistructured interview. Symptoms were self-rated on a combined form of the von Zerssen Complaints List, psychiatric disorders were assessed in the computerised WHO composite International Diagnostic Interview. In 29 persons no psychiatric disorder was diagnosed. In 25 persons mostly anxiety disorders and depressive disorders were found. 21 of the latter reported that the onset of symptoms was during imprisonment or within a one-year period following it. Many persons had some symptoms of post traumatic stress disorder while only one fulfilled all criteria for diagnosing it. Only a few variables were significantly correlated with the severity of self-rated symptoms or with the existence of a psychiatric disorder. The shared variance was limited. Former prisoners with a better vocational integration had less often a psychiatric disorder and fewer symptoms. When interviewes stated some positive implications of imprisonment for their life thereafter and when they had more social contacts, this was also associated with a lower severity of self-rated symptoms.

Aged↗
PubMed1997

The DnaJ domain of polyomavirus large T antigen is required to regulate Rb family tumor suppressor function.

Tumor suppressors of the retinoblastoma susceptibility gene family regulate cell growth and differentiation. Polyomavirus large T antigens (large T) bind Rb family members and block their function. Mutations of large T sequences conserved with the DnaJ family affect large T binding to a cellular DnaK, heat shock protein 70. The same mutations abolish large T activation of E2F-containing promoters and Rb binding-dependent large T activation of cell cycle progression. Cotransfection of a cellular DnaJ domain blocks wild-type large T action, showing that the connection between the chaperone system and tumor suppressors is direct. Although they are inactive in assays dependent on Rb family binding, mutants in the J region retain the ability to associate with pRb, p107, and p130. This suggests that binding of Rb family members by large T is not sufficient for their inactivation and that a functional J domain is required as well. This work connects the DnaJ and DnaK molecular chaperones to regulation of tumor suppressors by polyomavirus large T.

3T3 Cells↗
PubMed1997

Purification of the simian virus 40 (SV40) T antigen DNA-binding domain and characterization of its interactions with the SV40 origin.

To better define protein-DNA interactions at a eukaryotic origin, the domain of simian virus 40 (SV40) large T antigen that specifically interacts with the SV40 origin has been purified and its binding to DNA has been characterized. Evidence is presented that the affinity of the purified T antigen DNA-binding domain for the SV40 origin is comparable to that of the full-length T antigen. Furthermore, stable binding of the T antigen DNA-binding domain to the SV40 origin requires pairs of pentanucleotide recognition sites separated by approximately one turn of a DNA double helix and positioned in a head-to-head orientation. Although two pairs of pentanucleotides are present in the SV40 origin, footprinting and band shift experiments indicate that binding is limited to dimer formation on a single pair of pentanucleotides. Finally, it is demonstrated that the T antigen DNA-binding domain interacts poorly with single-stranded DNA.

Antigens, Polyomavirus Transforming↗
PubMed1997

[Ophthalmologic signs in children with autism].

PURPOSE: Autism is a clinical entity defined by characteristic association of a lack of social interactions and communications, beginning before three years of age. The purpose of this study was to screen ophthalmologic findings in autistic children. MATERIALS AND METHODS: Ten autistic children, 6 girls and 4 boys, underwent a complete ophthalmologic examination in the Department of Pediatric Ophthalmology at the Hospital La Timone, Marseilles, France. Their age ranged from 1 to 14 years (mean = 8.5 +/- 3.8). RESULTS: Refraction showed hypermetropia in 7 cases (70%), astigmatism more than 1 diopter in 6 cases (60%), bilateral astigmatism in 4 cases (40%) and unilateral astigmatism in 2 cases (20%). Astigmatism axis was oblique for 8 eyes, with the rule for 6 eyes and against the rule for 2 eyes. Strabismus was present in 6 cases (60%) including 4 cases of exotropia. Fundus examination found pallor of the optic disc in 4 cases. CONCLUSION: Ophthalmologic findings in autistic children appear to be mainly unilateral or bilateral astigmatism and binocular vision troubles. They can lead to amblyopia with the risk of functional loss of vision. Early diagnosis of visual problems in autistic children is also essential in order to be able to propose adequate psychological and educational cares for the children and their family.

Adolescent↗
PubMed1996

Oxidative inactivation of human 5-lipoxygenase in phosphatidylcholine vesicles.

Human 5-lipoxygenase is a non-heme iron protein which possesses 5-oxygenase, leukotriene A4 synthase and pseudoperoxidase activities and which undergoes a rapid irreversible inactivation during these reactions. The inactivation of the enzyme was dependent on the structural characteristics of the substrate for the reaction, on O2 concentration and on exposure to phospholipids and calcium. The apparent first-order rate constant for enzyme inactivation (k(in)) was 0.6 min(-1) during the oxygenation of arachidonic acid in air-saturated buffer containing phosphatidylcholine vesicles and Ca2+. The rate of enzyme inactivation was dependent on the substrate for the reaction and was about threefold slower during the oxygenation of 5,8-icosadienoic acid and 12(S)-hydroxyicosatetraenoic acid compared with arachidonic acid. Lowering the 02 concentration to 60 microM during the oxygenation of arachidonic acid also caused a 2.5-fold decrease in k(in) without affecting the initial rate of the reaction resulting in an increase in both 5-hydroperoxyicosatetraenoic acid (5-HPETE) and leukotriene A4 accumulation. The concentration of 02 for half-maximal activity (initial rate and product accumulation) was approximately 10 microM. In contrast, the activity and the rate of inactivation during the leukotriene A4 synthase reaction with exogenous 5-HPETE (k(in)=2.0 min(-1) were independent of 02 concentration. A rapid inactivation of the enzyme was also observed during aerobic incubation with phosphatidylcholine vesicles and Ca2+ in the absence of substrate, with a sequential loss of the oxygenase (t1/2 = 0.5 min) and pseudoperoxidase (t1/2 = 7 min) activities. Protection against this turnover-independent inactivation was observed in the presence of the selective reversible 5-lipoxygenase inhibitor L-739,010 ([1S, 5R] 3-cyano-1-(3-furyl)-6-(6-[3-(3 alpha-hydroxy-6,8-dioxyabicyclo [3.2.11 octanyl)] pyridin-2-ylmethoxy) naphthalene) and by prior treatment of vesicles with sodium borohydride and, to a lesser extent, by glutathione peroxidase. The results show that the inactivation of 5-lipoxygenase in phospholipid vesicles is dependent on the structure of the unsaturated fatty acid substrate for the reaction, on the concentration of oxygen and on a turnover-independent oxidation at the active-site leading to the sequential loss of the oxygenase and pseudoperoxidase activities of the enzyme.

Calcium↗
PubMed1996

Ocular findings in children operated on for plagiocephaly and trigonocephaly.

Clinical examination of patients affected by plagiocephaly or trigonocephaly reveals evident malformation of the orbits, and the ocular repercussions are pronounced when children are operated on at an advanced age. Since it is generally accepted that binocular vision is fully developed by approximately 6 months of age, a late correction of plagiocephalic or trigonocephalic skull deformities may be an obstacle to the development of normal visual function. For the present report we investigated astigmatism and strabismus in 53 children, 39 of whom were operated on for plagiocephaly and 14 for trigonocephaly. Traction on the ocular globe induced by the bony deformation caused by the craniosynostosis may explain astigmatism and strabismus.

Astigmatism↗
PubMed1995

Characterization of the arachidonate and ATP binding sites of human 5-lipoxygenase using photoaffinity labeling and enzyme immobilization.

The arachidonic acid and the ATP binding sites of human 5-lipoxygenase were characterized using photoaffinity labeling and immobilization of the enzyme on ATP-agarose. Photoaffinity labeling of the active site of 5-lipoxygenase was achieved with a novel thiopyranoindole inhibitor containing a 4-azido-3-iodobenzenesulfonyl moiety (L-708,714). This probe was found to inhibit the activity of 5-lipoxygenase (IC50 = 0.3 microM) and to covalently label the enzyme after UV light irradiation. The labeling was inhibited by arachidonic acid, N-hydroxyurea, and dihydrobenzofuranol inhibitors which have been shown to reduce the non-heme iron center of 5-lipoxygenase. Photoaffinity labeling of 5-lipoxygenase by L-708,714 was dependent on the presence of both Ca2+ ions and phospholipids and was independent of ATP. It occurred at similar levels using native (Fe2+), oxidized (Fe3+), or H2O2-inactivated enzyme, but was abolished by heat inactivation of the enzyme. Competition of the labeling by various thiopyranoindoles and other inhibitors such as L-697,198,ZD-2138, and zileuton was found to be related to their inhibitory potency. Immobilized 5-lipoxygenase on ATP-agarose was found to be selectively eluted by adenine nucleotides (ATP > ADP > AMP) but not by solutions containing high salt concentrations, mild detergents, arachidonic acid, or inhibitors. 5-Lipoxygenase inhibitors were selectively retained on the immobilized enzyme and eluted by buffer containing arachidonic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗
PubMed1995

Measurement of facial growth in the human fetus.

BACKGROUND: The fetal face is clearly seen by ultrasonography: we considered measurement of certain orbitofacial parameters of interest in the human fetus in order to establish norms for facial development. METHODS: We included 108 "normal" fetuses ranging in age from 16.5 to 41 weeks of amenorrhea. The orbitofacial parameters studied were outer canthal distance, inner canthal distance, oropalpebral distance right side and left side, and palpebral fissure length side and left side. The ocular parameters studied were corneal horizontal diameter and axial length. The traditional anthropometric parameters of the fetus were determined by pathological examination: age, weight head circumference and height. A statistical study analyzed the different correlations and established linear regression equations for orbitofacial parameters as a function of age. Polynomial regression models were tested to the third degree as a function of age and the head circumference/II ratio. RESULTS: Results are given in six different age groups. We find excellent correlation between the different parameters. Statistically valid linear regression equations were established for orbitofacial parameters. Polynomial regression equations were compared to linear equations their correlation coefficient and standard error, but showed no greater validity. Skull growth is more rapid than facial growth, which itself is more rapid vertically than horizontally. CONCLUSION: This study establishes norms for the different orbitofacial parameters, in particular the oropalpebral distance, for which we found no bibliographic references. The general interest of these measures lies in the description of malformation syndromes.

Anthropometry↗