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Biomedical subjects

A Martel

Publications and source records attributed to A Martel.

At least 37 records · Page 2Linked to original sources
PubMed2000

Contrast-reduced imaging of tissue concentration and arterial level (CRITICAL) for assessment of cerebral hemodynamics in acute stroke by magnetic resonance.

RATIONALE AND OBJECTIVES: To compare cerebral perfusion data obtained by using a low-dose, T1-weighted MRI technique with radionuclide (single positron emission computed tomography [SPECT]) brain imaging and to assess the reproducibility of parametric MRI data (cerebral blood flow [CBF], cerebral blood volume [CBV], and time to peak [TTP]) by applying a previously described nuclear medicine technique to derive quantitative perfusion data. METHODS: Single-slice brain and neck images were rapidly acquired during the passage of a small (1/10th of normal dose) bolus of contrast. Parametric images were constructed from the MR data by extracting the bolus transit curve for the brain and the peak arterial input curve from the carotid vessels in the neck. These were compared with SPECT perfusion imaging. Twenty-four patients with acute stroke were studied with both techniques; 13 underwent repeated scanning to assess data reproducibility. RESULTS: Relative CBF data were comparable to SPECT data (r = 0.584, P = 0.01). Results were reproducible for relative CBF, CBV, and TTP. The arterial input function was significantly different on the second injection with an average difference of 73.5, suggesting that the signal-concentration relationship had lost linearity with increased contrast load. Absolute quantitative MRI data produced values in the expected range (CBF = 42.6 mL x 100 g(-1) x min(-1)). CONCLUSIONS: This technique allows estimation of CBF in the setting of acute stroke with quantitative values in the expected range. Repeated measurements in the same patients showed that this technique provides a reproducible measure of relative CBF, CBV, and TTP.

Brain↗
PubMed1999

Novel quinolizidine salicylamide influenza fusion inhibitors.

A novel series of quinolizidine salicylamides was synthesized as specific inhibitors of the H1 subtype of influenza A viruses. These inhibitors inhibit the pH-induced fusion process, thereby blocking viral entry into host cells. Compound 16 was the most active inhibitor in this series with an EC50 of 0.25 microg/mL in plaque reduction assay. The synthesis and the SAR of these compounds are discussed.

Animals↗
PubMed1998

Purification and characterization of the main pepsinogen from the shark, Centroscymnus coelolepis.

The main pepsinogen from the mucosa of the shark, Centroscymnus coelolepis, has been purified and characterized. This zymogen, the most abundant protein in terms of quantity and activity (yield 72%), is a homogeneous monomer of molecular weight 42+/-0.7 kDa, as determined by electrophoresis. The aspartyl proteinase nature of this enzyme was confirmed by the considerable inhibition by pepstatin. Its specificity as to the oxidized B-chain of bovine insulin was determined using electrospray ionization mass spectrometry (ESI-MS) coupled with reversed phase high pressure liquid chromatography (RP-HPLC). The 15-16 Leu-Tyr bond was rapidly cleaved in this substrate, followed by the 24-25 Phe-Phe, 25-26 Phe-Tyr, and 11-12 Leu-Val bonds.

Amino Acid Sequence↗
PubMed1998

Direct sulfhydrylation for methionine biosynthesis in Leptospira meyeri.

A gene library of the Leptospira meyeri serovar semaranga strain Veldrat S.173 DNA has been constructed in a mobilizable cosmid with inserts of up to 40 kb. It was demonstrated that a Leptospira DNA fragment carrying metY complemented Escherichia coli strains carrying mutations in metB. The latter gene encodes cystathionine gamma-synthase, an enzyme which catalyzes the second step of the methionine biosynthetic pathway. The metY gene is 1,304 bp long and encodes a 443-amino-acid protein with a molecular mass of 45 kDa as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The deduced amino acid sequence of the Leptospira metY product has a high degree of similarity to those of O-acetylhomoserine sulfhydrylases from Aspergillus nidulans and Saccharomyces cerevisiae. A lower degree of sequence similarity was also found with bacterial cystathionine gamma-synthase. The L. meyeri metY gene was overexpressed under the control of the T7 promoter. MetY exhibits an O-acetylhomoserine sulfhydrylase activity. Genetic, enzymatic, and physiological studies reveal that the transsulfuration pathway via cystathionine does not exist in L. meyeri, in contrast to the situation found for fungi and some bacteria. Our results indicate, therefore, that the L. meyeri MetY enzyme is able to perform direct sulfhydrylation for methionine biosynthesis by using O-acetylhomoserine as a substrate.

Amino Acid Sequence↗
PubMed1998

Efficacy and safety of oral levofloxacin compared with clarithromycin in the treatment of acute sinusitis in adults: a multicentre, double-blind, randomized study. The Canadian Sinusitis Study Group.

Adult patients with acute sinusitis (n = 236) were randomized in a double-blind study to levofloxacin 500 mg orally once daily (n = 119) or clarithromycin 500 mg orally twice daily (n = 117) for 10-14 days. Between 2 and 5 days after therapy participants were evaluated as cured (no symptoms), improved (symptoms improved, no further therapy required), or failed (further therapy required). Clinical response rates (cured plus improved) for clinically evaluable patients were 93.9% for levofloxacin (n = 98) and 93.5% for clarithromycin (n = 93). The proportion of patients evaluated as cured was higher in the levofloxacin (40.8%) than in the clarithromycin arm (29.0%) and individual symptoms showed higher rates of resolution. Of patients receiving levofloxacin and clarithromycin, 22.5% and 39.3%, respectively, experienced adverse events related or possibly related to the study therapy. This study showed that, in the treatment of acute sinusitis, daily levofloxacin therapy is as effective as twice-daily clarithromycin therapy with more complete clearing of symptoms and a more tolerable side-effect profile.

Acute Disease↗
PubMed1997

Mass spectrometric determination of the cleavage sites in Escherichia coli dihydroorotase induced by a cysteine-specific reagent.

Escherichia coli dihydroorotase contains six cysteines/subunit, which are potential ligands of structural and catalytic zinc metals at protein sites of the enzyme. Specific thiol reagents modify, in nondenaturing conditions only, two of these cysteines; these two residues are thought to be ligands of structural zinc. We report here on the localization of these two cysteines on the polypeptide chain through their cyanylation by 2-nitro-5-thiocyanobenzoic acid (NTCB) and the analysis by mass spectrometry of the protein adducts. This is the first study of E. coli dihydroorotase by mass spectrometry, allowing the accurate determination of the subunit molecular weight (38,695). Treatment of dihydroorotase by NTCB induced a cleavage N-terminal to the cyanylated cysteines. The resulting fragments visualized on electrophoresis gel have been N-terminal sequenced, and their masses were determined by electrospray-ionizing mass spectrometry. This allowed the identification of cysteines 221 and 265 as the two residues cyanylated by the reagent NTCB. Results from gel filtration of dihydroorotase cyanylated on the two cysteines indicate that these residues are involved in subunit interactions leading to the active dimer. Consistent with literature data, we assume that cysteine 221 and cysteine 265, along with the neighboring cysteines 263 and 268 arranged in cluster, are potential ligands of structural zinc of E. coli dihydroorotase.

Binding Sites↗
PubMed1997

Sulfated galactocerebrosides as potential antiinflammatory agents.

Native sulfatides, as well as many sulfated glycolipids, have been shown to avidly bind to the selectin receptors. In vivo, native sulfatides significantly block activity in selectin-dependent inflammatory responses. The fact that nonsulfated galactocerebrosides did not inhibit selectin-mediated adhesion identified a critical role for the anionic sulfate residue. We therefore initiated a program to evaluate the activity of position isomers. This study showed a binding selectivity for the positions 2 and 3 of the sulfate group on the carbohydrate ring as well as enhanced activity for the disulfated analogs. Furthermore, it was discovered that the attachment of lipophilic substituents on the carbohydrate ring was tolerated, consistent with the presence of a lipophilic pocket in the binding activity. This resulted in compounds with a 6-fold increased potency.

Animals↗
PubMed1997

Homoserine O-acetyltransferase, involved in the Leptospira meyeri methionine biosynthetic pathway, is not feedback inhibited.

The Leptospira meyeri serovar semaranga metX gene was identified by complementation of an Escherichia coli metA mutant, i.e., devoid of homoserine O-succinyltransferase. However, the MetX protein exhibited a homoserine O-acetyltransferase activity in agreement with its similarity to homoserine O-acetyltransferases. Reverse transcription-PCR analysis demonstrated that metX is the second gene of an operon.

Acetyltransferases↗
PubMed1997

BMS-190394, a selectin inhibitor, prevents rat cutaneous inflammatory reactions.

Selectin binding is the first step in extravasation of leukocytes through the endothelium. Infiltration of leukocytes is a hallmark of an inflammatory response. Blockade of selectin-dependent adhesion, therefore, represents a specific mechanism-based anti-inflammatory strategy. We have used the natural product sulfatide, one of the selectin ligands, as a template to design a novel selectin antagonist. BMS-190394, a structural analog of sulfatide, is an inhibitor of cell binding to P-, E- and L-selectin-Ig fusion proteins. BMS-190394 also inhibits binding mediated by native P-selectin expressed on the surface of activated platelets. Pharmacokinetic analysis of BMS-190394 showed that the compound remained in circulation with a T1/2 of 7 hr, long enough to inhibit the development of an acute inflammatory response. The in vitro activity and pharmacokinetic profile of this selectin-blocking compound led to the determination of its in vivo anti-inflammatory activity. BMS-190394 was a potent inhibitor of the dermal immune complex-induced reverse passive Arthus reaction in rats when delivered by the i.v. or i.p. route. The ED50 of the compound in the reverse passive Arthus reaction compares favorably to that for dexamethasone. BMS-190394 was also an effective inhibitor of the delayed-type hypersensitivity reaction in the rat. Compared with previous reports of the use of antibodies and complex oligosaccharides to inhibit the activity of the selectins, this low-molecular-weight inhibitor of the selectins presents a novel class of anti-inflammatory agents.

Animals↗
PubMed1996

Assay of Escherichia coli dihydroorotase with enantiomeric substrate: practical preparation of carbamyl L-aspartate and high-performance liquid chromatography analysis of catalysis product.

A reasonably facile and effective procedure is described for preparing the optically active substrate of dihydroorotase (EC 3.5.2.3), N-carbamyl-L-aspartate (L-CA), which is not commercially available. Compared to the previously described methods, this procedure is not plagued by side reactions, and the L-CA is obtained in a solid form as the Mg2+/K+ mixed salt. In that salt form, the L-CA can be prepared in large quantity, and it is easier to handle and stable upon storage. L-CA can be separated from aspartate and its cyclic derivatives, dihydroorotate and hydantoin, by HPLC using a strong anion-exchange column. This HPLC method, which is used to check the purity of the synthesized carbamyl aspartate, is also effective for monitoring the enzymatic reaction.

Aspartic Acid↗
PubMed1994

Treatment of complicated urinary tract infections with lomefloxacin compared with that with trimethoprim-sulfamethoxazole.

The efficacy of lomefloxacin given at 400 mg once daily for 14 days compared with that of trimethoprim-sulfamethoxazole at 160 and 800 mg, respectively, given twice daily for 14 days in the treatment of symptomatic complicated urinary tract infections was studied in a prospective, randomized, single-blind multicenter study. A total of 133 subjects presenting with signs and symptoms of urinary tract infection and an underlying abnormality consistent with complicated urinary tract infection were enrolled in the study. Bacteriologic cure was significantly better in 68 subjects randomized to lomefloxacin than in 65 subjects randomized to trimethoprim-sulfamethoxazole at short-term follow-up (88 versus 52%; 95% confidence intervals [CIs] 77 and 94% and 39 and 65%, respectively) this difference was no longer significant at long-term follow-up (64 versus 47%; CIs, 52 and 75% and 32 and 57%, respectively). Clinical outcomes were similar for both therapeutic regimens at short- and long-term follow-ups. The organisms that infected the subjects pretherapy were more frequently resistant to trimethoprim-sulfamethoxazole, and drug therapy was discontinued more frequently in subjects treated with trimethoprim-sulfamethoxazole because of adverse antimicrobial effects. In secondary analyses, outcomes did not differ with age or underlying genitourinary abnormality.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Pyridoxal 5'phosphate binding site of Escherichia coli beta cystathionase and cystathionine gamma synthase comparison of their sequences.

The phosphopyridoxyl peptides of beta cystathionase and cystathionine gamma synthase of Escherichia Coli were identified after reduction, carboxymethylation and proteolysis of the holoenzymes. Their comparison with those obtained from rat liver gamma cystathionase (Fearon, C.W., Rodkey, J.A. and Abeles R.H. 1982. Biochemistry 21 3790-3794.) showed a high degree of homology between the three PLP binding sites with the presence of the tripeptide sequence: Thr-Lys(Pxy)-Tyr in their structure. This homology suggests that these enzymes of methionine metabolism have probably the same origin.

Amino Acid Sequence↗
PubMed1986

Evolution in biosynthetic pathways: two enzymes catalyzing consecutive steps in methionine biosynthesis originate from a common ancestor and possess a similar regulatory region.

The metC gene of Escherichia coli K-12 was cloned and the nucleotide sequence of the metC gene and its flanking regions was determined. The translation initiation codon was identified by sequencing the NH2-terminal part of beta-cystathionase, the MetC gene product. The metC gene (1185 nucleotides) encodes a protein having 395 amino acid residues. The 5' noncoding region was found to contain a "Met box" homologous to sequences suggestive of operator structures upstream from other methionine genes that are controlled by the product of the pleiotropic regulatory metJ gene. The deduced amino acid sequence of beta-cystathionase showed extensive homology with that of the MetB protein (cystathionine gamma-synthase) that catalyzes the preceding step in methionine biosynthesis. The homology strongly suggests that the structural genes for the MetB and MetC proteins evolved from a common ancestral gene.

Amino Acid Sequence↗
PubMed1984

Renaturation of the allosteric phosphofructokinase from Escherichia coli.

The allosteric phosphofructokinase from Escherichia coli has been renatured after complete unfolding in concentrated guanidine hydrochloride. The enzyme regains both its catalytic and regulatory abilities quantitatively. The kinetics of reactivation are biphasic and are consistent with a two-step mechanism in which a monomolecular reaction precedes a bimolecular one. The presence of ATP during reactivation increases the rate at which phosphofructokinase is renatured; the second order rate constant of the bimolecular step increases from about 10(4) M-1 S-1 in the absence of ATP to about 2 X 10(5) M-1 S-1 in the presence of 1 mM ATP. The other ligands of the enzyme have no effect on reactivation. It is tentatively proposed that a folded monomer is the intermediate species which already possesses a functional ATP-binding site and that the rate-limiting association step is the formation of dimeric species. This interpretation is compatible with the known three-dimensional structure of another bacterial phosphofructokinase, that from Bacillus stearothermophilus.

Adenosine Triphosphate↗
PubMed1984

Role of subunit interactions in the self-assembly of oligomeric proteins.

In oligomeric proteins, the native conformation and its functional properties depend on the interactions which exist between the different chains. The role of these subunit interactions can be studied using either the unfolded state or the native state as a starting point. During the folding process, the properties which appear following a bimolecular reaction are related to the formation of an association area. Similarly, the properties which are lost upon partial dissociation of the native state are related to the association area which is disrupted. Four examples are presented in this article: phosphofructokinase and aspartokinase-homoserine dehydrogenase from E. coli are studied through their folding process, and fatty acid synthetase from B. ammoniagenes and reptilian ovomacroglobulin are studied through their dissociated forms. In all cases, the function of the protein is a sensitive index of the formation of the subunit interactions, and can be more conveniently measured than other size/shape parameters. The extrapolation from the folding of small proteins to the assembly of large and complex structures can be reasonably achieved by admitting that subunit interactions are coupled to the subtle adjustments required by the protein to exert its biological function.

Animals↗
PubMed1983

Kinetic studies of aminoglycoside acetyltransferase and phosphotransferase from Staphylococcus aureus RPAL. Relationship between the two activities.

In the Staphylococcus aureus strain harbouring the plasmid RPAL, the resistance to aminoglycoside antibiotics results from two inactivating reactions catalyzed by a 6'-N-aminoglycoside acetyltransferase and a 2"-O-amino-glycoside phosphotransferase. These enzymes are copurified with a constant ratio between the two activities, the purification process consisting in affinity chromatography, native electrophoresis and gel exclusion chromatography. The kinetic mechanisms of each activity have been determined from studies of initial velocities, as well as product and dead-end inhibitions. Both activities follow a random rapid equilibrium mechanism. The substrates and cofactors of one reaction have been tested as effectors of the other reaction. No interaction between the two activities has been observed. However, the GTP cofactor of phosphotransferase protects, at weak concentrations, the acetyltransferase against thermal inactivation, which suggests that the two activities may be associated.

Acetyltransferases↗
PubMed1982

[Urological problems related to aorto-bifemoral surgery (author's transl)].

The authors reviewed, from a urological standpoint, the records of 400 patients undergoing aorto-bifemoral bypass between 1967 and 1980. Stenosing or aneurysmal lesions of the renal arteries were present in 106 patients, i.e. 26.5% of cases. 7% of the patients had previous pathology (2 lithiasis, 4 hydronephrosis and one non-functioning kidney). All the operations consisted of a bypass inserted posterior to the peritoneum and ureters. 39 patients (9.7%) underwent simultaneous surgery on the renal artery or vein, or the kidney, Amongst a total of 12% deaths, 1.5% were of renal causes. The postoperative urological morbidity was 24.9% being dominated by infectious lesions (16%) and ureteric lesions (5%). The majority of ureteric lesions took the form of progressive distension of the excretory apparatus. The presence of an indwelling urethral catheter was considered to be the most important factor in infection. The authors feel that it is essential to visualise the urinary tract at the time of angiographic investigation of aortoiliac disease. Amongst 18 cases of progressive dilatation of the upper urinary tract after such vascular surgery, only 3 underwent operation. Nevertheless, intravenous urography is an essential part of postoperative surveillance after surgery of this sort. Only 15% of their patients had undergone IVU and amongst them 18 were found to have a hydronephrosis.

Adult↗