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171.
Circular dichroism (CD) spectra in the region of 210-250 nm allow visualization of intrachain phase transition of pH- and thermosensitive polyelectrolytes. Indeed, in 0.001 M citrate and acetate buffers, at pH 4.0-5.5, aqueous solutions of a poly(N-isopropylacrylamide-co-N-methacryloyl-L-leucine) (NIPAAm-MALEU) copolymer containing 90.9 mol% of NIPAAm residues exhibit a well-defined sigmoidal increase in the CD signal at 220 nm with increasing temperature. This phenomenon is suggestive of a highly cooperative transition which occurs at lower temperatures compared to that observed by cloud point measurements. The change in the CD signal is less sharp at higher pH, indicating varying cooperativity with pH. For pH 6.0 and higher, no such phenomena are observed. 相似文献
172.
Ducharme Y Friesen RW Blouin M Côté B Dubé D Ethier D Frenette R Laliberté F Mancini JA Masson P Styhler A Young RN Girard Y 《Bioorganic & medicinal chemistry letters》2003,13(11):1923-1926
The synthesis and the phosphodiesterase-4 (PDE4) inhibitory activity of 2-pyridinemethanol derivatives is described. The evaluation of the structure-activity relationship (SAR) in this series of novel PDE4 inhibitors led to the identification of compound 9 which exhibits excellent in vitro activity, desirable pharmacokinetic parameters and good efficacy in animal models of bronchoconstriction. 相似文献
173.
174.
Lee JY Miraglia S Yan X Swartzman E Cornell-Kennon S Mellentin-Michelotti J Bruseo C France DS 《Journal of biomolecular screening》2003,8(1):81-88
High-throughput screening (HTS) for potential anticancer agents requires a broad portfolio of assay platforms that may include kinase enzyme assays, protein-protein binding assays, and functional cell-based apoptosis assays. The authors have explored the use of fluorometric microvolume assay technology (the FMAT 8100 HTS System) in three distinct homogeneous HTS assays: (1). a Src tyrosine kinase enzyme assay, (2). a Grb2-SH2 protein-peptide interaction assay, and (3). an annexin V binding apoptosis assay. Data obtained from all three assays suggest that the FMAT system should facilitate the implementation of homogeneous assays for a wide variety of molecular targeted and cell-based screens. 相似文献
175.
176.
Brenière SF Bosseno MF Noireau F Yacsik N Liegeard P Aznar C Hontebeyrie M 《Memórias do Instituto Oswaldo Cruz》2002,97(3):289-295
A cross section of a human population (501 individuals) selected at random, and living in a Bolivian community, highly endemic for Chagas disease, was investigated combining together clinical, parasitological and molecular approaches. Conventional serology and polymerase chain reaction (PCR) indicated an active transmission of the infection, a high seroprevalence (43.3%) ranging from around 12% in < 5 years to 94.7% in > 45 years, and a high sensitivity (83.8%) and specificity of PCR. Abnormal ECG tracing was predominant in chagasic patients and was already present among individuals younger than 13 years. SAPA (shed acute phase antigen) recombinant protein and the synthetic peptide R-13 were used as antigens in ELISA tests. The reactivity of SAPA was strongly associated to Trypanosoma cruzi infection and independent of the age of the patients but was not suitable neither for universal serodiagnosis nor for discrimination of specific phases of Chagas infection. Anti-R-13 response was observed in 27.5% only in chagasic patients. Moreover, anti-R13 reactivity was associated with early infection and not to cardiac pathology. This result questioned previous studies, which considered the anti-R-13 response as a marker of chronic Chagas heart disease. The major clonets 20 and 39 (belonging to Trypanosoma cruzi I and T. cruzi II respectively) which circulate in equal proportions in vectors of the studied area, were identified in patients' blood by PCR. Clonet 39 was selected over clonet 20 in the circulation whatever the age of the patient. The only factor related to strain detected in patients' blood, was the anti-R-13 reactivity: 37% of the patients infected by clonet 39 (94 cases) had anti-R13 antibodies contrasting with only 6% of the patients without clonet 39 (16 cases). 相似文献
177.
Bryn Duffy Chad Schwietert Alex France Niti Mann Krista Culbertson Benjamin Harmon John P. McCue 《Biological trace element research》1998,64(1-3):197-213
An alternative approach to the development of clinically useful protease inhibitors was investigated. The approach utilized
coordination chemistry of transition metal ions rather than substrate analogs to block active sites of these enzymes. In the
case of serine proteases it was found that aqueous Ti(IV) is a potent inhibitor of the trypsin subclass, but not the chymotrypsin
subclass. The direct binding of Ti(IV) to trypsin was made possible by the presence of a free carboxyl group at the bottom
of the substrate binding pocket of the enzyme, and the five-coordinate geometry of TiO(SO4)(H2O). Although initial binding of Ti(IV) was reversible, it was followed in time by irreversible inhibition. Direct binding
of octahedral or tetrahedral metal ion complexes was prevented by the inability of the enzyme active sites to promote formation
of a five-coordinate transition state of the metal ion required for reaction. These studies demonstrate the ability of direct
metal ion binding as a way to enhance blocking of enzyme active sites as compared with that of traditional organic inhibitors.
Application of these findings was investigated by measuring the affect Ti(IV) had on growth ofEscherichia coli, Salmonella typhimurium, andPseudotnonas aeruginosa. Five-coordinate titanyl sulfate completely inhibited the growth of these organisms. This suggests that five-coordinate titanyl
sulfate, which is easier and less expensive to manufacture than conventional antibiotics, may be useful in controlling endemic
infections ofE. coli andS. typhimurium. 相似文献
178.
Harry R. Davis Deborra E. Mullins Jesse M. Pines Lizbeth M. Hoos Constance F. France Douglas S. Compton Michael P. Graziano Edmund J. Sybertz Catherine D. Strader Margaret Van Heek 《Obesity (Silver Spring, Md.)》1998,6(2):147-156
Glucagon-like peptide (7–36) amide (GLP-1) acutely inhibits food and water consumption in rats after intrace-rebroventricular (icv) administration. To assess the potential for desensitization of these effects, we investigated the effects of chronic icv administration of GLP-1 on food consumption and body weight in Sprague-Dawley (SD) rats and Zucker (fa/fa) obese rats. In vitro functional densensitization of the GLP-1 receptor was not observed after overnight exposure of Rin m5F insulinoma cells to GLP-1 at concentrations up to 10 nM. Administration of GLP-1 to SD rats (30 ug icv twice a day for 6 days) resulted in significant reductions in 24-hour food consumption each day (25 ±1%). Continuous icv infusion of GLP-1 for 7 and 14 days significantly inhibited cumulative food consumption and reduced body weight in SD rats. In the genetically obese Zucker rat, chronic dosing with GLP-1 (30 ug icv) once a day for 6 days caused significant reductions in food consumption each day and a reduction in body weight. These results indicate that the GLP-1 pathways in the central nervous system controlling food consumption do not desensitize after chronic exposure to GLP-1 and suggest that agonists of the central GLP-1 receptor may be effective agents for the treatment of obesity. 相似文献
179.
Champagne Claude P. Gardner Nancy Dugal France 《Journal of industrial microbiology & biotechnology》1994,13(6):367-371
Summary Immobilized cell technology was used to prepare concentrated cultures ofLactococcus lactis that lost only 22% of viability over a 30-day storage period at 4°C. Concentrated cultures ofL lactis CRA-1 were immobilized in calcium alginate beads and added to glycerol, NaCl or sucrose-NaCl solutions in order to obtain aw readings ranging from 0.91 to 0.97. The suspensions were subsequently placed at 4°C and viability (CFU g–1 of bead) was followed during storage. Viability losses were high at aw readings of 0.95 and 0.97 and pH dropped significantly (up to one unit) in the unbuffered solutions. Addition of 1% soytone or glycerophosphate helphed stabilize pH, and a beneficial effect on viability during storage was observed in the glycerol-soytone mix when the beads were added to the conservation solutions immediately following immobilization. When beads were added to the conservation solution immediately following immobilization, a 70% drop in cell counts occurred during the first 5 days of incubation. Dipping theL lactis-carrying beads in milk for 2h before mixing with the glycerolsoytone 0.93 aw solution reduced this initial 5-day viability loss. Cultures grown in the alginate beads also had good stability in the 0.93 aw glycerol-soytone solution, where 78% of the population was viable after 30 days at 4°C. The process could be used to store immobilized cells at a processing plant, or by suppliers of lactic starters who wish to ship cultures without freezing or drying. 相似文献
180.
France Demaugre Claude Cepanec Jean-Paul Leroux 《Biochemical and biophysical research communications》1978,85(3):1180-1185
In isolated hepatocytes, dichloroacetate decreased glucose synthesis from lactate, pyruvate and alanine, but not from substrates which bypass pyruvate carboxylase (propionate, glycerol). It was also found to inhibit pyruvate carboxylation in isolated mitochondria, but only after a preincubation period, and had no effect on partially purified pyruvate carboxylase. Hepatocytes and liver mitochondria metabolized [14C] dichloroacetate to oxalate which inhibits pyruvate carboxylase and mimics, without preincubation, the effects of dichloroacetate in mitochondrial pyruvate carboxylation. Thus, oxalate appears to be responsible for the inhibition of gluconeogenesis by dichloroacetate at the level of pyruvate carboxylation. 相似文献