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Biomedical subjects

N Nassar

Publications and source records attributed to N Nassar.

28 records · Page 2Linked to original sources
PubMed1996

Ras/Rap effector specificity determined by charge reversal.

Members of the Ras subfamily of small GTP-binding proteins have been shown to be promiscuous towards a variety of putative effector molecules such as the protein kinase c-Raf and the Ral-specific guanine nucleotide exchange factor (Ral-GEF). To address the question of specificity of interactions we have introduced the mutations E30D and K31E into Rap and show biochemically, by X-ray structure analysis and by transfection in vivo that the identical core effector region of Ras and Rap (residues 32-40) is responsible for molecular recognition, but that residues outside this region are responsible for the specificity of the interaction. The major determinant for the switch in specificity is the opposite charge of residue 31--Lys in Rap, Glu in Ras--which creates a favourable complementary interface for the Ras-Raf interaction.

Amino Acid Sequence↗
PubMed1996

Therapeutic effect of reference antileishmanial agents in murine visceral leishmaniasis due to Leishmania infantum.

A sensitive, culture-based, microtitration technique has recently been developed for determining parasite burdens in organs recovered from Balb/c mice infected with Leishmania infantum. In the present study, this technique was used to examine the efficacy of three, first-line, antileishmanial agents in reducing parasite burdens and eradicating parasites from target organs in mice. Treatment with meglumine antimoniate (50 mg SbV/kg.day) significantly reduced the parasite burdens in the livers and lungs (by about 10-fold and > 100-fold, respectively) but not those in the spleens. Although use of a higher dose of meglumine antimoniate (200 mg SbV/kg.day) resulted in an even more dramatic reduction in the parasite burdens in the livers, it had no significant effect on the burdens in the spleens. Treatment with amphotericin B (0.8 mg/kg every other day) resulted in significant reductions in the parasite burdens in the livers, spleens and lungs of infected mice. Although low doses of aminosidine (20 mg/kg.day) had no effect, high doses (200 mg/kg.day) resulted in undetectable parasite burdens in the livers, for at least 100 days post-treatment, and marked reductions in burdens in the spleens. These results are consistent with previous data from studies using animal models of visceral leishmaniasis. Thanks to the sensitivity of the technique, culture microtitration revealed that none of the drug schedules achieved the elimination of all parasites in all target organs. The murine model used mimics some important features of HIV/Leishmania infantum co-infections in humans.

Amphotericin B↗
PubMed1995

The 2.2 A crystal structure of the Ras-binding domain of the serine/threonine kinase c-Raf1 in complex with Rap1A and a GTP analogue.

The X-ray crystal structure of the complex between the Ras-related protein Rap1A in the GTP-analogue (GppNHp) form and the Ras-binding domain (RBD) of the Ras effector molecule c-Raf1, a Ser/Thr-specific protein kinase, has been solved to a resolution of 2.2 A. It shows that RBD has the ubiquitin superfold and that the structure of Rap1A is very similar to that of Ras. The interaction between the two proteins is mediated by an apparent central antiparallel beta-sheet formed by strands B1-B2 from RBD and strands beta 2-beta 3 from Rap1A. Complex formation is mediated by main-chain and side-chain interactions of the so-called effector residues in the switch I region of Rap1A.

Amino Acid Sequence↗
PubMed1995

Unexpected structural requirements for GTPase activity of the interferon-induced MxA protein.

MxA is an interferon-induced 76-kDa GTPase that inhibits the multiplication of several RNA viruses. Deleting seven amino acids from the COOH terminus reduced the GTPase activity of purified MxA to 1.4%. MxA mutants with COOH-terminal deletions of 63 or more amino acids lost all ability to hydrolyze GTP and failed to bind guanine nucleotides. By contrast, an MxA deletion mutant consisting of 301 amino acids from the NH2 terminus and 87 amino acids from the COOH terminus retained about 9% of wild-type GTPase activity, underscoring the pivotal role of COOH-terminal sequences. Limited proteolysis of wild-type MxA with proteinase K resulted in two resistant polypeptides of 60 and 10 kDa, respectively, which copurified as a stable complex. The p60-p10 complex exhibited high GTPase activity, suggesting that it included all MxA domains required for this biochemical activity. Sequencing revealed that the NH2 terminus of the 60-kDa polypeptide mapped to leucine 41 and the NH2 terminus of the 10-kDa polypeptide to glutamine 564 of the MxA sequence. Based on these results we propose a model that suggests that the GTP-binding consensus element located in the NH2-terminal half of MxA is held in an active conformation by strong physical interactions with amino acids from the COOH-terminal region.

Amino Acid Sequence↗
PubMed1994

In vitro activity of readily available household materials against HIV-1: is bleach enough?

This report describes experiments assessing the effectiveness against HIV of potential disinfecting agents that are commonly available to IDU when they are sharing syringes. We exposed cell-free HIV, HIV-infected cells, and HIV-infected blood containing known quantities of HIV to household cleaning agents, alcohols, peroxide, and highly acidic materials for 1 min, in order to examine the effects of these materials on the infectivity of the HIV. Undiluted liquid laundry bleach and dilute liquid dish detergent reduced the number of culturable HIV to an undetectable level under the experimental conditions used. Diluted bleach was not completely effective. Other potential disinfecting agents, including ethanol, isopropyl alcohol, and hydrogen peroxide, were unable to disinfect high numbers of HIV-infected cells or infected blood. Liquid dish detergent warrants further study as a possible acceptable alternative to bleach. Our data provide support for recommendations to IDU that they disinfect shared syringes every time between users with full-strength liquid laundry bleach to reduce their risk of acquiring or transmitting HIV. When bleach is not available, liquid dish detergent or other available disinfecting agents such as rubbing alcohol, hydrogen peroxide, or high alcohol content beverages are more effective than water at disinfecting HIV, recognizing that these materials are less effective than bleach. Although these materials are effective, they should not be viewed as a substitute for decreased sharing of injection equipment by IDU, or increased availability of sterile needles and syringes.

1-Propanol↗
PubMed1993

Cardiac function and responsiveness to beta-adrenoceptor agonists in rats with obstructive jaundice.

The function and role of the heart and the contribution of cardiac beta-adrenoceptors in the pathogenesis of circulatory failure in obstructive jaundice were studied in the 3-day bile duct-ligated (BDL) rat using three different techniques to measure cardiac function and beta-adrenoceptor activity, number, and affinity. The techniques were the pithed rat preparation, the isolated working heart preparation, and a competitive radioligand binding assay for beta-adrenoceptors. The results of these experiments were compared with those obtained in 3-day bile duct-manipulated (sham operated; SO) rats. Impaired indexes of basal cardiac contractility were observed in the BDL pithed rats and isolated working hearts. In these two preparations, responsiveness to norepinephrine and the beta-adrenoceptor agonists, isoproterenol and dobutamine, was unaffected by bile duct ligation. The affinity and number of cardiac beta-adrenoceptors in membranes from the hearts of SO and BDL rats were not significantly different from each other. These experiments have established for the first time that the 3-day BDL rat has a cardiac myopathy associated with intact responsiveness to beta-adrenoceptor agonists, a normal unchanged affinity and number of cardiac beta-adrenoceptors.

Adrenergic beta-Agonists↗
PubMed1990

A second class of synthetase structure revealed by X-ray analysis of Escherichia coli seryl-tRNA synthetase at 2.5 A.

The three-dimensional crystal structure of seryl-transfer RNA synthetase from Escherichia coli, refined at 2.5 A resolution, is described. It has an N-terminal domain that forms an antiparallel alpha helical coiled-coil, stretching 60 A out into the solvent and stabilized by interhelical hydrophobic interactions and an active-site alpha-beta domain based around a seven-stranded antiparallel beta sheet. Unlike the three other known synthetase structures, the enzyme contains no classical nucleotide-binding fold, and is the first representative of a second class of aminoacyl-tRNA synthetase structures.

Amino Acid Sequence↗
PubMed1986

[A new cause of acute transitory auriculoventricular block: Lyme disease].

A young man developed syncopal complete paroxysmal atrioventricular block (AVB) over a 36 hour period, on a background of 1st degree AVB which persisted for 6 weeks. During the 3rd week, electrophysiological studies showed an isolated prolonged AH interval. This episode followed skin and articular manifestations occurring one month after being bitten by a tick in Corsica. The clinical picture suggested Lyme's disease which was confirmed serologically. This condition transmitted bu Ixodes ricinus, a tick present in country districts, is due to spirochetal infection. It is characterized by a chronic migrating erythema, and may sometimes be complicated by severe AV conduction defects which are always regressive, as in our case.

Adult↗
PubMedDate not supplied

Ano-rectal lymphogranuloma venereum: 22 cases reported in a sexually transmited infections center in Paris.

In January 2004 the European Surveillance of Sexually Transmitted Infections Network (ESSTI) issued an international alert regarding an outbreak of Lymphogranuloma venereum (LGV) in Rotterdam in a sexual network of men who have sex with men (MSM). Further to this alert, a retrospective survey was set up by the Institut de Veille Sanitaire and the reference laboratories for N.gonorrhoeae and Chlamydia in France. Our STI clinic in Paris carried out a clinico-biological retrospective study involving 154 MSM screened for anorectal sexually transmitted infections (STIs) between January 2002 and May 2004 and a prospective study between May 2004 and August 2004. Out of 216 swabs of rectal discharge from homosexual or bisexual males, a total of 32 were positive for C. trachomatis (14.8%) (3 patients in 2002, 11 in 2003 and 18 in 2004). C. trachomatis-positive rectal strains were genotyped to detect the specific C. trachomatis serovars and revealed serovars L(2) for 22 patients (respectively 1 in 2002, 9 in 2003 and 12 in 2004). Serum antibody titers for Chlamydia trachomatis were determined among 14 subjects and revealed strongly positive in 13 cases (1/512 to 1/16384) titers of IgG. These 22 patients with clinico-biologically confirmed anorectal lymphogranuloma venereum (ARLGV) were all homosexual men. They ranged from 28 to 52 years (mean age 39.2 years). 12 of 21 (57.1%) subjects with an ARLGV diagnosis were seropositive for human immunodeficiency virus (HIV) (one not done). Although rare, anorectal lymphogranuloma venereum (ARLGV) still exists in France and should not be forgotten in the differential diagnosis of rectal problems in male homosexuals.

Adult↗