bluuebunny/crossref_metadata_2025_split huggingface dataset:
The synthesis and characterization of 2‐Trideuteriomethyl and 2,2‐Di(trideuteriomethyl) Aryl Ketones
Authors: Coumbarides Gregory S. , Eames Jason , Weerasooriya Neluka 
Published: October 2002

AbstractResults are reported on the synthesis and characterization of a variety of trideuteriomethyl aryl ketones. Copyright © 2002 John Wiley & Sons, Ltd.
Design and synthesis of fluorine‐18 labeled matrix metalloproteinase inhibitors for cancer imaging
Authors: Furumoto Shozo , Iwata Ren , Ido Tatsuo 
Published: October 2002

AbstractMatrix metalloproteinases (MMPs) are key enzymes involved in cancer invasion and metastasis. New 18F‐labeled MMP inhibitors (1a–c) has been designed and synthesized for cancer imaging by positron emmision tomography. The precursors were synthesized in four steps starting from D‐form of amino acids. Radiosynthesis of 1a–c were carried out by simple one‐pot synthesis. The resulting radiofluorinated MMP inhibitors were obtained in overall radiochemical yields of 13–43% (EOB, decay corrected) within 60–70 min (including final preparative HPLC separation). Copyright © 2002 John Wiley & Sons, Ltd.
tRNA discrimination by T. thermophilus phenylalanyl–tRNA synthetase at the binding step
Authors: Vasil'eva Inna A. , Ankilova Valentina N. , Lavrik Olga I. , Moor Nina A. 
Published: October 2002

AbstractThe extent of tRNA recognition at the level of binding by Thermus thermophilus phenylalanyl‐tRNA synthetase (PheRS), one of the most complex class II synthetases, has been studied by independent measurements of the enzyme association with wild‐type and mutant tRNAPhes as well as with non‐cognate tRNAs. The data obtained, combined with kinetic data on aminoacylation, clearly show that PheRS exhibits more tRNA selectivity at the level of binding than at the level of catalysis. The anticodon nucleotides involved in base‐specific interactions with the enzyme prevail both in the initial binding recognition and in favouring aminoacylation catalysis. Tertiary nucleotides of base pair G19‐C56 and base triple U45‐G10‐C25 contribute primarily to stabilization of the correctly folded tRNAPhe structure, which is important for binding. Other nucleotides of the central core (U20, U16 and of the A26‐G44 tertiary base pair) are involved in conformational adjustment of the tRNA upon its interaction with the enzyme. The specificity of nucleotide A73, mutation of which slightly reduces the catalytic rate of aminoacylation, is not displayed at the binding step. A few backbone‐mediated contacts of PheRS with the acceptor and anticodon stems revealed in the crystal structure do not contribute to tRNAPhe discrimination, their role being limited to stabilization of the complex. The highest affinity of T. thermophilus PheRS for cognate tRNA, observed for synthetase–tRNA complexes, results in 100–3000‐fold binding discrimination against non‐cognate tRNAs. Copyright © 2002 John Wiley & Sons, Ltd.
DAPI binding to the DNA minor groove: a continuum solvent analysis
Authors: De Castro L. F. Pineda , Zacharias M. 
Published: October 2002

AbstractA continuum solvent model based on the generalized Born (GB) or finite‐difference Poisson–Boltzmann (FDPB) approaches has been employed to compare the binding of 4′‐6‐diamidine‐2‐phenyl indole (DAPI) to the minor groove of various DNA sequences. Qualitative agreement between the results of GB and FDPB approaches as well as between calculated and experimentally observed trends regarding the sequence specificity of DAPI binding to B‐DNA was obtained. Calculated binding energies were decomposed into various contributions to solvation and DNA–ligand interaction. DNA conformational adaptation was found to make a favorable contribution to the calculated total interaction energy but did not change the DAPI binding affinity ranking of different DNA sequences. The calculations indicate that closed complex formation is mainly driven by nonpolar contributions and was found to be disfavored electrostatically due to a desolvation penalty that outbalances the attractive Coulomb interaction. The calculated penalty was larger for DAPI binding to GC‐rich sequences compared with AT‐rich target sequences and generally larger for the FDPB vs the GB continuum model. A radial interaction profile for DAPI at different distances from the DNA minor groove revealed an electrostatic energy minimum a few Angstroms farther away from the closed binding geometry. The calculated electrostatic interaction up to this distance is attractive and it may stabilize a nonspecific binding arrangement. Copyright © 2002 John Wiley & Sons, Ltd.
NG‐nitro‐L‐arginine methylester, a nitric oxide synthase inhibitor, diminishes apoptosis induced by ischemia‐reperfusion in the rat bladder
Authors: Saito Motoaki , Miyagawa Ikuo 
Published: October 2002

AbstractAims.To evaluated the effects of NG‐nitro‐L‐arginine methylester (L‐NAME), a nitric oxide synthase (NOS) inhibitor, on apoptosis induced by ischemia‐reperfusion injury in the rat through a muscle bath and TUNEL staining.Methods.The rat abdominal aorta was clamped to induce ischemia‐reperfusion (I‐R) injury in the rat bladder dome with or without L‐NAME (30 mg/kg, i.p. 30 minutes before the ischemia) according to our previous reports [Saito et al., 1998 Life Sci. 62:PL149–56; Saito and Miyagawa, 1999 J. Urol. 162:1490–5]. Some rats were exposed to 30 minutes of ischemia only, whereas others also received 30 minutes, 3 days, or 7 days of reperfusion after the ischemia. Muscle bath studies with carbachol and 100 mM KCl were performed to confirm the bladder function. TUNEL and hematoxylin and eosin staining were performed in the experimental rat bladders to detect apoptosis.Results.The contractile responses of the rat bladder dome after 30 minutes of ischemia differed slightly, not significantly, from those of controls. Reperfusion (30 minutes) produced significant reductions in the contractile responses to carbachol and KCl in the rat bladders. The treatment with L‐NAME significantly reduced the extent of reperfusion injury, as judged by pharmacologic experiments. At 3 and 7 days after the induction of ischemia‐reperfusion, the contractile responses were improved compared with the 30‐minute reperfusion group. For each duration group, treatment with L‐NAME significantly increased the contractile responses compared with the I‐R group without L‐NAME. Ischemia‐reperfusion induced apoptosis, and the peak in TUNEL‐positive cells was observed 3 days after the insult. Preteatment with L‐NAME reduced the induction of apoptosis.Conclusion.Our data indicated treatment with L‐NAME can reduce apoptosis induced by ischemia‐reperfusion in the bladder. Neurourol. Urodynam. 21:566–571, 2002. © 2002 Wiley‐Liss, Inc.
Urodynamic evaluation of the human bladder response tgo an increase in outlet resistance
Authors: Engel Jason D. , Jacobs Dan , Konsur Bogdan , Megaridis Constantine M. , Bushman Wade 
Published: October 2002

AbstractAim.We prospectively evaluated the response of the human bladder to a chronic increase in urethral resistance according to the indices of pressure, volume flow rate, total (external) bladder work, and maximum and average detrusor power.Methods.Six men with incontinence after radical prostatectomy were evaluated urodynamically before and 3–6 months after undergoing a bulbourethral sling procedure.Results.None of the men suffered from significant obstructive or irritative voiding symptoms preoperatively. Urodynamic evaluation showed postoperative increases in both average detrusor pressure and pressure at maximum flow, but there were no significant changes in voided volume, void time, or postvoid residual urine volume. Maximum detrusor power, average detrusor power, and total (external) bladder work were all significantly increased.Conclusion.These data confirm that the human bladder possesses a functional reserve, which is elicited by an increase in urethral resistance. Neurourol. Urodynam. 21:524–528, 2002. © 2002 Wiley‐Liss, Inc.
Zebrafish as a model for hearing and deafness
Authors: Whitfield Tanya T. 
Published: October 2002

AbstractThe zebrafish is an especially attractive model for the study of the development and function of the vertebrate inner ear. It combines rapid and accessible embryogenesis with a host of genetic and genomic tools for systematic gene discovery and analysis. A large collection of mutations affecting development and function of the ear and a related sensory system, the lateral line, have been isolated; several of these have now been cloned, and at least five provide models for human deafness disorders. Disruption of multiple genes, using both forward and reverse genetic approaches, has established key players—both signaling molecules and autonomous factors—responsible for induction and specification of the otic placode. Vestibular and auditory defects have been detected in adult animals, making the zebrafish a useful system in which to tackle the genetic causes of late onset deafness and vestibular disease. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 157–171, 2002
Development of the inner ear efferent system across vertebrate species
Authors: Simmons Dwayne D. 
Published: October 2002

AbstractInner ear efferent neurons are part of a descending centrifugal pathway from the hindbrain known across vertebrates as the octavolateralis efferent system. This centrifugal pathway terminates on either sensory hair cells or eighth nerve ganglion cells. Most studies of efferent development have used either avian or mammalian models. Recent studies suggest that prevailing notions of the development of efferent innervation need to be revised. In birds, efferents reside in a single, diffuse nucleus, but segregate according to vestibular or cochlear projections. In mammals, the auditory and vestibular efferents are completely separate. Cochlear efferents can be divided into at least two distinct, descending medial and lateral pathways. During development, inner ear efferents appear to be a specific motor neuron phenotype, but unlike motor neurons have contralateral projections, innervate sensory targets, and, at least in mammals, also express noncholinergic neurotransmitters. Contrary to prevailing views, newer data suggest that medial efferent neurons mature early, are mostly, if not exclusively, cholinergic, and project transiently to the inner hair cell region of the cochlea before making final synapses on outer hair cells. On the other hand, lateral efferent neurons mature later, are neurochemically heterogeneous, and project mostly, but not exclusively to the inner hair cell region. The early efferent innervation to the ear may serve an important role in the maturation of afferent responses. This review summarizes recent data on the neurogenesis, pathfinding, target selection, innervation, and onset of neurotransmitter expression in cholinergic efferent neurons. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 228–250, 2002
Whole‐body nutrient composition of various ages of captive‐bred bearded dragons (Pogona vitteceps) and adult wild anoles (Anolis carolinensis)
Authors: Cosgrove Jennifer J. , Beermann Donald H. , House William A. , Toddes Barbara D. , Dierenfeld Ellen S. 
Published: October 2002

AbstractNeonates, 11‐day‐old, and 17‐day‐old captive‐bred bearded dragons (Pogona vitteceps) and wild‐caught adult anoles (Anolis carolinensis) were chemically analyzed to determine the whole‐body concentrations of vitamins E and A, crude protein, and minerals. Significant differences (P<0.05) were noted between neonates and older age groups of the bearded dragons for concentrations of all the minerals except calcium (Ca) and phosphorus (P). The neonatal animals generally exhibited lower concentrations of all minerals, except for magnesium (Mg) and iron (Fe), than did the older lizards. The concentration of vitamin E was higher, and that of vitamin A was lower in neonates than in older animals. The whole‐body concentrations of protein, vitamins A and E, Ca, P, potassium (K), sodium (Na), copper (Cu), and manganese (Mn) differed significantly between the bearded dragons and anoles. Zoo Biol 21:489–497, 2002. © 2002 Wiley‐Liss, Inc.
Epidemiological study of suicide in the Republic of Croatia – comparison of war and post-war periods and areas directly and indirectly affected by war
Authors: Grubišić-Ilić Mirjana , Kozarić-Kovačić Dragica , Grubišić Frane , Kovačić Zrnka 
Published: October 2002

SummaryWe examined the differences in the suicide characteristics between areas directly and indirectly affected by war activities and in war and post-war periods according to the following variables: suicide rate, sex, age and method of suicide. Analysis was done on 5349 suicides committed in the period 1993–1998 (war and post-war years). The suicide rates in the Republic of Croatia oscillated in the pre-war, war and post-war periods (1985–2000) but without significant differences. In the areas directly affected by war, the suicide rate was significantly lower than in other areas during the study period 1993–1998 (chi-square = 10.3245;P= 0.0017). The number of suicides in both sexes declined in the areas directly affected by war—more in men than in women; the difference between sexes was statistically significant (chi-square = 3.6697;P= 0.055). Middle- and old-aged people were the population with high suicide risk in both areas (t= 1.76;P= 0.078). There were significant differences in the methods of suicides between war and non-war areas (chi-square = 108.8473;P= 0.001). Firearms or explosive devices were the methods used more significantly for suicides in the areas directly affected by war than in other areas, whereas hanging was more frequently used in the areas indirectly affected by war.
Life events and changes in the course of depression in young adults
Authors: Friis Robert H. , Wittchen Hans-Ulrich , Pfister Hildegard , Lieb Roselind 
Published: October 2002

SummaryBackground.Few community-based studies have examined the impact of life events, life conditions and life changes on the course of depression. This paper examines associations of life events on depressive symptom onset, improvement, and stability.Methods.Direct interview data from the Early Developmental Stages of Psychopathology Study (EDSP), a 4–5 year prospective-longitudinal design based on a representative community sample of adolescents and young adults, aged 14–24 years at baseline, are used. Life events were measured using the Munich Event-Questionnaire (MEL) consisting of 83 explicit items from various social role areas and subscales for the assessment of life event clusters categorized according to dimensions such as positive and negative and controllable and uncontrollable. Depressive disorders were assessed with the DSM-IV version of the Munich Composite Diagnostic Interview (M-CIDI). Multiple logistic regression analyses examined the effects of 22 predictors on the course of depression (onset, improvement, stability).Results.Younger age, low social class, negative and stressful life events linked to the family were associated with increased risk of new onset of depression. Anxiety was a significant independent predictor of new onset of depression. Absence of stressful school and family events was related to improvement in depression. The weighted total number of life events predicted stable depression.Conclusions.The association between life events and the course of depression appears to vary according to the outcome being examined, with different clusters of life events differentially predicting onset, improvement, and stability.
Interaction of Avilamycin with Ribosomes and Resistance Caused by Mutations in 23S rRNA
Authors: Kofoed Christine B. , Vester Birte 
Published: October 2002

ABSTRACT

The antibiotic growth promoter avilamycin inhibits protein synthesis by binding to bacterial ribosomes. Here the binding site is further characterized on
Escherichia coli
ribosomes. The drug interacts with domain V of 23S rRNA, giving a chemical footprint at nucleotides A2482 and A2534. Selection of avilamycin-resistant
Halobacterium halobium
cells revealed mutations in helix 89 of 23S rRNA. Furthermore, mutations in helices 89 and 91, which have previously been shown to confer resistance to evernimicin, give cross-resistance to avilamycin. These data place the binding site of avilamycin on 23S rRNA close to the elbow of A-site tRNA. It is inferred that avilamycin interacts with the ribosomes at the ribosomal A-site interfering with initiation factor IF2 and tRNA binding in a manner similar to evernimicin.
gyrA
and
gyrB
Mutations Are Implicated in Cross-Resistance to Ciprofloxacin and Moxifloxacin in
Clostridium difficile
Authors: Dridi Larbi , Tankovic Jacques , Burghoffer Béatrice , Barbut Frédéric , Petit Jean-Claude 
Published: October 2002

ABSTRACT

A total of 198 nonrepetitive clinical strains of
Clostridium difficile
isolated from different French hospitals in 1991 (
n
= 100) and 1997 (
n
= 98) were screened for decreased susceptibility to fluoroquinolones by plating onto Wilkins-Chalgren agar containing 16 μg of ciprofloxacin per ml. The frequency of decreased susceptibility was 7% (14 of 198) and was identical for the years 1991 and 1997. Serogroups C, H, D, A9, and K accounted for five, four, two, one, and one of the resistant strains, respectively, one strain being nontypeable. Arbitrarily primed PCR typing showed that all resistant strains had unique patterns except two serotype C strains, which could not be clearly distinguished. All isolates with decreased susceptibility carried a mutation either in
gyrA
(eight mutations, amino acid changes Asp71→Val in one, Thr82→Ile in six, and Ala118→Thr in one) or in
gyrB
(six mutations, amino acid changes Asp426→Asn in five and Arg447→Leu in one). These changes are similar to those already described in other species except for Asp71→Val, which is novel, and Ala118→Thr, which is exceptional. Attempts to detect the topoisomerase IV
parC
gene by PCR amplification with universal
parC
primers or DNA-DNA hybridization under low-stringency conditions were unsuccessful. The susceptibilities of all resistant strains to ciprofloxacin and ethidium bromide were not affected by the addition of reserpine at 20 μg/ml. In conclusion, decreased susceptibility to fluoroquinolones in
C. difficile
is rare in France and is associated with the occurrence of a
gyrA
or
gyrB
mutation.
Dexamethasone, a Drug for Attenuation ofSchistosoma mansoniInfection Morbidity
Authors: Pyrrho Alexandre dos Santos , Ramos Juliene Antonio , Neto Roberto Moura , Silva Célia Santos da , Lenzi Henrique Leonel , Takiya Christina Maeda , Gattass Cerli Rocha 
Published: October 2002

ABSTRACTTo investigate the possible use of immunomodulators as coadjuvants in the treatment of chronic schistosomiasis, the study described in the present report evaluated the effects of dexamethasone on several parameters which reflect disease severity and morbidity. Parasitological, immunological, and histological parameters were analyzed in animals treated from the first day of infection or after 35 days of infection. In both situations, dexamethasone had no effect on the parasite burden but altered the egg distribution in tissue, indicating that under the schedule used it did not interfere with the development of adult worms or oviposition. Treated mice showed a decrease in the number of eggs in hepatic tissue, reduced granuloma sizes, reduced levels of granuloma maturation, and reduced collagen contents. Dexamethasone-treated mice also had decreased gamma interferon, interleukin-12 (IL-12), and IL-4 levels in serum and increased IL-10 levels in serum. Taken together, these data suggested a decrease in the severity of murine schistosomiasis and point to dexamethasone as a convenient and promising coadjuvant agent in the therapy of this infection.
Low-Virulence
Citrobacter
Species Encode Resistance to Multiple Antimicrobials
Authors: Pepperell C. , Kus J. V. , Gardam M. A. , Humar A. , Burrows L. L. 
Published: October 2002

ABSTRACT

Citrobacter
spp. are gram-negative commensal bacteria that infrequently cause serious nosocomial infections in compromised hosts. They are often resistant to cephalosporins due to overexpression of their chromosomal β-lactamase. During a recent study of multidrug-resistant
Enterobacteriaceae
(MDRE) in solid-organ transplant patients, we found that almost half of patients colonized with MDRE carried one or more cefpodoxime-resistant
Citrobacter freundii
,
Citrobacter braakii
, or
Citrobacter amalonaticus
strains. Pulsed-field gel electrophoresis showed that 36 unique strains of
Citrobacter
were present among 32 patients. Genetic and phenotypic analysis of the resistance mechanisms of these bacteria showed that the extended-spectrum β-lactamase (ESBL) SHV-5 or SHV-12 was encoded by 8 strains (26%) and expressed by 7 strains (19%). A number of strains were resistant to other drug classes, including aminoglycosides (28%), trimethoprim-sulfamethoxazole (31%), and fluoroquinolones (8%). PCR and DNA analysis of these multiresistant strains revealed the presence of class I integrons, including the first integrons reported for
C. braakii
and
C. amalonaticus
. The integrons encoded aminoglycoside resistance, trimethoprim resistance, or both. Despite the prevalence of MDR
Citrobacter
spp. in our solid-organ transplant patients, only a single infection with a colonizing strain was recorded over 18 months. Low-virulence
Citrobacter
spp., which can persist in the host for long periods, could influence pathogen evolution by accumulation of genes encoding resistance to multiple antimicrobial classes.
Stampidine Is a Potent Inhibitor of Zidovudine- and Nucleoside Analog Reverse Transcriptase Inhibitor-Resistant Primary Clinical Human Immunodeficiency Virus Type 1 Isolates with Thymidine Analog Mutations
Authors: Uckun Fatih M. , Pendergrass Sharon , Venkatachalam T. K. , Qazi Sanjive , Richman Douglas 
Published: October 2002

ABSTRACT

We report the antiretroviral activity of stavudine-5′-(
p
-bromophenyl methoxyalaninyl phosphate) (stampidine [STAMP]), a novel aryl phosphate derivative of stavudine, against primary clinical human immunodeficiency virus type 1 (HIV-1) isolates. STAMP inhibited each one of nine clinical HIV-1 isolates of non-B envelope subtype and 20 genotypically and phenotypically nucleoside analog reverse transcriptase inhibitor-resistant HIV-1 isolates at subnanomolar to low-nanomolar concentrations.