bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reactivity of peptidyl‐tyrosine to hydroxylation and cross‐linking
Authors: Burzio Luis A. , Waite J. Herbert 
Published: July 2002

AbstractTyrosine residues of neuroendocrine peptides are frequently the targets of oxidation reactions, one of which involves hydroxylation to peptidyl‐3, 4‐dihydroxy‐phenyl‐L‐alanine (DOPA). The reactivity in vitro of peptidyl‐DOPA in two neuroendocrine peptides, a neurotensin fragment (pELYENK) and proctolin (RYLPT), was investigated using ultraviolet‐visible scanning spectrophotometry and matrix‐assisted laser desorption ionization mass spectrometry following oxidation by tyrosinase and periodate. The peptides form covalently coupled dimers and trimers, and their masses are consistent with the presence of diDOPA cross‐links. Lysine does not appear to participate in multimer formation because it is efficiently recovered in fragmentation ladders using subtilisin. While multimer formation in the neurotensin‐derived peptide can be blocked effectively by adding N‐acetyl‐DOPA‐ethylester to the reaction medium, the DOPA ethylester couples itself four to five times to each peptide.
X‐ray structure of a novel matrix metalloproteinase inhibitor complexed to stromelysin
Authors: Dunten Pete , Kammlott Ursula , Crowther Robert , Levin Wayne , Foley Louise H. , Wang Ping , Palermo Robert 
Published: July 2002

AbstractA new class of matrix metalloproteinase (MMP) inhibitors has been identified by screening a collection of compounds against stromelysin. The inhibitors, 2,4,6‐pyrimidine triones, have proven to be potent inhibitors of gelatinases A and B. An X‐ray crystal structure of one representative compound bound to the catalytic domain of stromelysin shows that the compounds bind at the active site and ligand the active‐site zinc. The pyrimidine triones mimic substrates in forming hydrogen bonds to key residues in the active site, and provide opportunities for placing appropriately chosen groups into the S1′ specificity pocket of MMPs. A number of compounds have been synthesized and assayed against stromelysin, and the variations in potency are explained in terms of the binding mode revealed in the X‐ray crystal structure.
Thermodynamic analysis of the binding of component enzymes in the assembly of the pyruvate dehydrogenase multienzyme complex of Bacillus stearothermophilus
Authors: Jung Hyo‐Il , Bowden Simon J. , Cooper Alan , Perham Richard N. 
Published: July 2002

AbstractThe peripheral subunit‐binding domain (PSBD) of the dihydrolipoyl acetyltransferase (E2, EC 2.3.1.12) binds tightly but mutually exclusively to dihydrolipoyl dehydrogenase (E3, EC 1.8.1.4) and pyruvate decarboxylase (E1, EC 1.2.4.1) in the pyruvate dehydrogenase multienzyme complex of Bacillus stearothermophilus. Isothermal titration calorimetry (ITC) experiments demonstrated that the enthalpies of binding (ΔH°) of both E3 and E1 with the PSBD varied with salt concentration, temperature, pH, and buffer composition. There is little significant difference in the free energies of binding (ΔG° = −12.6 kcal/mol for E3 and = −12.9 kcal/mol for E1 at pH 7.4 and 25°C). However, the association with E3 was characterized by a small, unfavorable enthalpy change (ΔH° = +2.2 kcal/mol) and a large, positive entropy change (TΔS° = +14.8 kcal/mol), whereas that with E1 was accompanied by a favorable enthalpy change (ΔH° = −8.4 kcal/mol) and a less positive entropy change (TΔS° = +4.5 kcal/mol). Values of ΔCp of −316 cal/molK and −470 cal/molK were obtained for the binding of E3 and E1, respectively. The value for E3 was not compatible with the ΔCp calculated from the nonpolar surface area buried in the crystal structure of the E3‐PSBD complex. In this instance, a large negative ΔCp is not indicative of a classical hydrophobic interaction. In differential scanning calorimetry experiments, the midpoint melting temperature (Tm) of E3 increased from 91°C to 97.1°C when it was bound to PSBD, and that of E1 increased from 65.2°C to 70.0°C. These high Tm values eliminate unfolding as a major source of the anomalous ΔCp effects at the temperatures (10–37°C) used for the ITC experiments.
Effects of Shot-Peening on Fretting-Fatigue Behavior of Ti-6Al-4V
Authors: Namjoshi S. A. , Jain V. K. , Mall S. 
Published: July 2002

AbstractThe effects of shot-peening on the fretting fatigue behavior of titanium alloy, Ti-6Al-4V were investigated. Specimens were shot-peened as per AMS 2432 standard. X-ray diffraction analysis measured a maximum compressive stress of 800 MPa at the specimen surface, which reduced to zero at a depth of 188 μm. The compensatory residual tensile stress in the specimen was estimated using a curve fitting technique, the maximum value of which was found to be 260 MPa at a depth of 255 μm. Fretting fatigue tests were conducted at room temperature at a cyclic frequency of 200 Hz. Scanning electron microscopy of the shot-peened fretting fatigue specimens showed that the crack initiated at a point below the contact surface, the depth of which was in the range of 200–300 μm. Finite element analysis of the fretting fatigue specimens was also conducted. Fatigue life diagrams were established for the fretting fatigue specimens with and without shot-peening, and were compared to those under the plain fatigue condition, i.e. without fretting. Shot-peening improved the fretting fatigue life of Ti-6Al-4V; furthermore, it moved the crack initiation site from the fretting contact region to a region inside the specimen. Moreover, stress analysis showed that the fatigue failure of shot-peened specimens was caused by the compensatory tensile residual stress.
Effect of Annular Incision Type on the Change in Biomechanical Properties in a Herniated Lumbar Intervertebral Disc
Authors: Natarajan R. N. , Andersson G. B. J. , Patwardhan A. G. , Verma S. 
Published: July 2002

AbstractThe technique used to incise the disc during discectomy may play a role in the subsequent healing and change in biomechanical stiffness of the disc. Several techniques of lumbar disc annulotomy have been described in clinical reports. The purpose of this paper was to study the influence of annulotomy technique on motion segment stiffness using a finite element model. Four incision methods (square, circular, cross, and slit) were compared. The analyses showed that each of the annular incisions produced increase in motions under axial moment loadings with circular incision producing the largest change in the corresponding rotational motion. Under shear loading mode, cross and slit-type annular incisions produced slightly larger changes in the principal motions of the disc than square and circular incisions. All other incision types considered in the current study produced negligibly small increase in motion under rest of the loading conditions. In addition to annulotomy, when nucleotomy was also included in the analyses, once again cross and slit incisions produced larger change in motion under shear loading mode as compared to the other two incision types. A comparison between the four types of annular incisions showed that cross incision produced an increase in motion larger than those produced by the other three incisions under flexion/extension and lateral moment loading and both shear force loadings. Circular incision produced the largest increase in motion under axial moment load in comparison to those produced by square, cross, and slit incisions. Sagittal plane symmetry was influenced by the incision injury to the motion segment leading to coupled motions as well as increased facet loads. From the study it can be concluded that the increase in flexibility of the disc due to annulotomy depends on the type of annulotomy, and the annulotomy also produce asymmetrical deformations leading to increased facet loading.
Turbine Engine Performance Improvements—A Proactive Approach
Authors: Gastineau Zane D. 
Published: July 2002

Abstract
Turbine engine concepts for the future are placing ever increasing demands on the design engineer. These future systems are seeking to increase performance while at the same time reduce costs. However, traditional engine design methods use large margins in the design process of a specific component in order to guarantee proper operation throughout the flight envelope over the life of the engine. These margins in fact reduce engine performance and increase the costs. In this paper, active control will be presented as one potential means of achieving the requirements for future turbine engines. In addition, specific active control applications will be discussed.
Characterization of Passage-Selected Vancomycin-Resistant
Staphylococcus aureus
Strains of Diverse Parental Backgrounds
Authors: Pfeltz Richard F. , Singh Vineet K. , Schmidt Jennifer L. , Batten Michael A. , Baranyk Christopher S. , Nadakavukaren Matthew J. , Jayaswal Radheshyam K. , Wilkinson Brian J. 
Published: July 2002

ABSTRACT

A series of 12
Staphylococcus aureus
strains of various genetic backgrounds, methicillin resistance levels, and autolytic activities were subjected to selection for the glycopeptide-intermediate
S. aureus
(GISA) susceptibility phenotype on increasing concentrations of vancomycin. Six strains acquired the phenotype rapidly, two did so slowly, and four failed to do so. The vancomycin MICs for the GISA strains ranged from 4 to 16 μg/ml, were stable to 20 nonselective passages, and expressed resistance homogeneously. Neither ease of acquisition of the GISA phenotype nor the MIC attained correlated with methicillin resistance hetero- versus homogeneity or autolytic deficiency or sufficiency. Oxacillin MICs were generally unchanged between parent and GISA strains, although the
mec
members of both isogenic methicillin-susceptible and methicillin-resistant pairs acquired the GISA phenotype more rapidly and to higher MICs than did their susceptible counterparts. Transmission electron microscopy revealed that the GISA strains appeared normal in the absence of vancomycin but had thickened and diffuse cell walls when grown with vancomycin at one-half the MIC. Common features among GISAs were reduced doubling times, decreased lysostaphin susceptibilities, and reduced whole-cell and zymographic autolytic activities in the absence of vancomycin. This, with surface hydrophobicity differences, indicated that even in the absence of vancomycin the GISA cell walls differed from those of the parents. Autolytic activities were further reduced by the inclusion of vancomycin in whole-cell and zymographic studies. The six least vancomycin-susceptible GISA strains exhibited an increased capacity to remove vancomycin from the medium versus their parent lines. This study suggests that while some elements of the GISA phenotype are strain specific, many are common to the phenotype although their expression is influenced by genetic background. GISA strains with similar glycopeptide MICs may express individual components of the phenotype to different extents.
Resistance to Mercury and Antimicrobial Agents in
Streptococcus mutans
Isolates from Human Subjects in Relation to Exposure to Dental Amalgam Fillings
Authors: Leistevuo Jorma , Järvinen Helinä , Österblad Monica , Leistevuo Tiina , Huovinen Pentti , Tenovuo Jorma 
Published: July 2002

ABSTRACT

Resistance to cefuroxime, penicillin, tetracycline, and mercury is reported for 839
Streptococcus mutans
isolates from 209 human study subjects. The MICs of these drugs did not differ for isolates from one dental amalgam group and two nonamalgam subsets: a group with no known exposure to amalgam and a group whose members had their amalgam fillings removed.
Pharmacokinetics of SCH 56592, a New Azole Broad-Spectrum Antifungal Agent, in Mice, Rats, Rabbits, Dogs, and Cynomolgus Monkeys
Authors: Nomeir Amin A. , Kumari Pramila , Hilbert Mary Jane , Gupta Samir , Loebenberg David , Cacciapuoti Anthony , Hare Roberta , Miller George H. , Lin Chin-Chung , Cayen Mitchell N. 
Published: July 2002

ABSTRACT
SCH 56592 is a new broad-spectrum azole antifungal agent that is in phase 3 clinical trials for the treatment of serious systemic fungal infections. The pharmacokinetics of this drug candidate were evaluated following its intravenous (i.v.) or oral (p.o.) administration as a solution in hydroxypropyl-β-cyclodextrin (HPβCD) or oral administration as a suspension in 0.4% methylcellulose (MC) in studies involving mice, rats, rabbits, dogs, and cynomolgus monkeys. SCH 56592 was orally bioavailable in all species. The oral bioavailability was higher with the HPβCD solution (range, 52 to ∼100%) than from the MC suspension (range, 14 to 48%) and was higher in mice (∼100% [HPβCD] and 47% [MC]), rats (∼66% [HPβCD] and 48% [MC]), and dogs (72% [HPβCD] and 37% [MC]) than in monkeys (52% [HPβCD] and 14% [MC]). In rabbits, high concentrations in serum suggested good oral bioavailability with the MC suspension. The i.v. terminal-phase half-lives were 7 h in mice and rats, 15 h in dogs, and 23 h in monkeys. In rabbits, the oral half-life was 9 h. In species given increasing oral doses (mice, rats, and dogs), serum drug concentrations were dose related. Food produced a fourfold increase in serum drug concentrations in dogs. Multiple daily doses of 40 mg of SCH 56592/kg of body weight for eight consecutive days to fed dogs resulted in higher concentrations in serum, indicating accumulation upon multiple dosing, with an accumulation index of approximately 2.6. Concentrations above the MICs and minimum fungicidal concentrations for most organisms were observed at 24 h following a single oral dose in MC suspension in all five species studied (20 mg/kg for mice, rats, and rabbits and 10 mg/kg for dogs and monkeys), suggesting that once-daily administration of SCH 56592 in human subjects would be a therapeutically effective dosage regimen.
Pefloxacin-Induced Achilles Tendon Toxicity in Rodents: Biochemical Changes in Proteoglycan Synthesis and Oxidative Damage to Collagen
Authors: Simonin Marie-Agnes , Gegout-Pottie Pascale , Minn Alain , Gillet Pierre , Netter Patrick , Terlain Bernard 
Published: July 2002

ABSTRACT

Despite a relatively low incidence of serious side effects, fluoroquinolones and the fluoroquinolone pefloxacin have been reported to occasionally promote tendinopathy that might result in the complication of spontaneous rupture of tendons. In the present study, we investigated in rodents the intrinsic deleterious effect of pefloxacin (400 mg/kg of body weight) on Achilles tendon proteoglycans and collagen. Proteoglycan synthesis was determined by measurement of in vivo and ex vivo radiosulfate incorporation in mice. Collagen oxidative modifications were measured by carbonyl derivative detection by Western blotting. An experimental model of tendinous ischemia (2 h) and reperfusion (3 days) was achieved in rats. Biphasic changes in proteoglycan synthesis were observed after a single administration of pefloxacin, consisting of an early inhibition followed by a repair-like phase. The depletion phase was accompanied by a marked decrease in the endogenous serum sulfate level and a concomitant increase in the level of sulfate excretion in urine. Studies of ex vivo proteoglycan synthesis confirmed the in vivo results that were obtained. The decrease in proteoglycan anabolism seemed to be a direct effect of pefloxacin on tissue metabolism rather than a consequence of the low concentration of sulfate. Pefloxacin treatment for several days induced oxidative damage of type I collagen, with the alterations being identical to those observed in the experimental tendinous ischemia and reperfusion model. Oxidative damage was prevented by coadministration of
N
-acetylcysteine (150 mg/kg) to the mice. These results provide the first experimental evidence of a pefloxacin-induced oxidative stress in the Achilles tendon that altered proteoglycan anabolism and oxidized collagen.
Antimalarial Bioavailability and Disposition of Artesunate in Acute Falciparum Malaria
Authors: Newton Paul , Suputtamongkol Yupin , Teja-Isavadharm Paktiya , Pukrittayakamee Sasithon , Navaratnam V , Bates Imelda , White Nicholas 
Published: July 2002

ABSTRACT

The pharmacokinetic properties of oral and intravenous artesunate (2 mg/kg of body weight) were studied in 19 adult patients with acute uncomplicated
Plasmodium falciparum
malaria by using a randomized crossover design. A sensitive bioassay was used to measure the antimalarial activity in plasma which results from artesunate and its principal metabolite, dihydroartemisinin. The oral study was repeated with 15 patients during convalescence. The mean absolute oral bioavailability of the antimalarial agent in patients with acute malaria was 61% (95% confidence interval [CI], 52 to 70%). The absorption and elimination of oral artesunate were rapid, with a mean elimination half-life of antimalarial activity of 43 min (95% CI, 33 to 53 min). Following oral administration to patients with acute falciparum malaria, peak antimalarial activity in plasma and the area under the plasma concentration-time curve were approximately double those during convalescence and the apparent volume of distribution and clearance were approximately half those during convalescence (
P
≤ 0.005). Acute malaria is associated with a significant reduction in the clearance of artesunate-associated antimalarial activity.
Evernimicin Binds Exclusively to the 50S Ribosomal Subunit and Inhibits Translation in Cell-Free Systems Derived from both Gram-Positive and Gram-Negative Bacteria
Authors: McNicholas Paul M. , Najarian David J. , Mann Paul A. , Hesk David , Hare Roberta S. , Shaw Karen J. , Black Todd A. 
Published: July 2002

ABSTRACT

Evernimicin (SCH 27899) is a new antibiotic with activity against a wide spectrum of gram-positive bacteria and activity against some gram-negative bacteria. Previous metabolic labeling studies indicated that evernimicin specifically inhibited protein synthesis in
Staphylococcus aureus
. Using a susceptible
Escherichia coli
strain, we demonstrated that evernimicin also inhibited protein synthesis in
E. coli
. In cell-free translation assays with extracts from either
E. coli
or
S. aureus
, evernimicin had a 50% inhibitory concentration of approximately 125 nM. In contrast, cell-free systems derived from wheat germ and rabbit reticulocytes were inhibited only by very high levels of evernimicin. Evernimicin did not promote transcript misreading. [
14
C]evernimicin specifically bound to the 50S subunit from
E. coli
. Nonlinear regression analysis of binding data generated with 70S ribosomes from
E. coli
and
S. aureus
and 50S subunits from
E. coli
returned dissociation constants of 84, 86, and 160 nM, respectively. In binding experiments, performed in the presence of excess quantities of a selection of antibiotics known to bind to the 50S subunit, only the structurally similar drug avilamycin blocked binding of [
14
C]evernimicin to ribosomes.
Geographic Distribution of a Large Mobile Element That Transfers Ampicillin and Vancomycin Resistance between
Enterococcus faecium
Strains
Authors: Hanrahan Jennifer , Hoyen Claudia , Rice Louis B. 
Published: July 2002

ABSTRACT

In several clonally unrelated VanB-type vancomycin-resistant
Enterococcus faecium
strains, we demonstrated a common physical relationship between
pbp5
and Tn
5382
as well as common mutations within
pbp5
. The majority of these strains transferred vancomycin and ampicillin resistance to
E. faecium
in vitro, suggesting the dissemination of similar transferable
pbp5-vanB
-containing mobile elements throughout the United States.
Pharmacokinetics and Tolerability of Gemifloxacin (SB-265805) after Administration of Single Oral Doses to Healthy Volunteers
Authors: Allen Ann , Bygate Elizabeth , Oliver Stuart , Johnson Martin , Ward Christopher , Cheon Ae-Jin , Choo Youn Sung , Kim In-Chull 
Published: July 2002

ABSTRACT

Gemifloxacin (known as SB-265805 or LB-20304) is a potent, novel fluoroquinolone compound with a broad spectrum of antibacterial activity. The pharmacokinetics and tolerability of oral gemifloxacin were characterized in healthy male volunteers after a single dose of 20, 40, 80, 160, 320, 600, or 800 mg. Multiple serum and urine samples were collected and analyzed for gemifloxacin using high-performance liquid chromatography with fluorescence detection. Safety assessments included vital signs, 12-lead electrocardiogram readings, hematology, clinical chemistry, urinalysis, and adverse-experience monitoring. Gemifloxacin was rapidly absorbed after all doses. Maximum concentrations of gemifloxacin in serum (
C
max
) were achieved approximately 1 h after dosing, after which concentrations in serum declined in a biexponential manner. Values of
C
max
and the area under the concentration-time curve in serum from 0 h to infinity (serum AUC
0–∞
) increased linearly with dose. Serum AUC
0–∞
values (mean ± standard deviation) were 0.65 ± 0.01, 1.28 ± 0.22, 2.54 ± 0.31, 5.48 ± 1.24, 9.82 ± 2.70, 24.4 ± 7.1, and 31.4 ± 7.6 μg · h/ml following 20-, 40-, 80-, 160-, 320-, 600-, and 800-mg doses, respectively. The terminal phase elimination half-life was independent of dose, with an overall mean of 7.4 ± 2.0 h. The profiles indicated that the pharmacokinetic profile is suitable for a once-daily dosing regimen. Approximately 25 to 40% of the administered dose was excreted unchanged in the urine, and renal clearance (ca. 150 ml/min) was independent of dose. There were no significant changes in clinical chemistry, hematology, or urinalysis parameters, vital signs, or 12-lead electrocardiogram readings in subjects, irrespective of dose. The results of these studies support the further investigation of once-daily administration of gemifloxacin.
Characterization of a Variant of
vga
(A) Conferring Resistance to Streptogramin A and Related Compounds
Authors: Haroche Julien , Allignet Jeanine , Buchrieser Carmen , El Solh Névine 
Published: July 2002

ABSTRACT

A variant of the
vga
(A) gene (1,575 bp), encoding an ATP-binding cassette protein conferring resistance to streptogramin A and related antibiotics, was cloned from the chromosome of a
Staphylococcus aureus
clinical isolate and sequenced. The sequence of the variant was similar to that of the
vga
(A) gene (83.2% identity). However, the G+C content of the variant (35.6%) was higher than that of
vga
(A) (29%) and there was no cross hybridization between
vga
(A) and the variant at high stringency (≥60°C), the highest temperature at which a signal was detected being 55°C. Unlike previous reports for
vga
(A) and
vga
(B), the variant of
vga
(A) may be present in multiple copies in the genome. These copies are chromosomal in some isolates and both chromosomal and plasmid-borne in others. Nucleotide sequences hybridizing at 65°C with the
vga
(A) variant were found in all the staphylococcal strains harboring plasmids carrying both
vga
(B) and
vat
(B), which also encode resistance to streptogramin A.
Drug Interaction Studies of a Glucan Synthase Inhibitor (LY 303366) and a Chitin Synthase Inhibitor (Nikkomycin Z) for Inhibition and Killing of Fungal Pathogens
Authors: Stevens David A. 
Published: July 2002

ABSTRACT

The interaction between inhibitors of components of the fungal cell wall, glucan and chitin, was studied in vitro with the respective synthase enzyme inhibitors LY 303366 and nikkomycin Z. With
Aspergillus fumigatus
synergy was noted for inhibition and killing, and synergistic activity was also noted for some isolates of other species presently regarded as difficult to treat.