bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decreased haloperidol‐induced potentiation of zif268 mRNA expression in the nucleus accumbens shell and the dorsal lateral striatum of rats lacking cholecystokinin‐A receptors
Authors: Shilling P.D. , Feifel D. 
Published: August 2002

AbstractEvidence suggests that endogenous cholecystokinin (CCK), a neuropeptide that modulates brain dopamine function, may contribute to the therapeutic and motor effects of antipsychotic drugs via activation of CCK‐A receptors in the mesolimbic and nigrostriatal pathways, respectively. To determine if CCK modulates the effects of antipsychotic drugs through CCK‐A receptors, we measured the haloperidol‐induced zif268 mRNA response in the nucleus accumbens (NA) shell, NA core, and dorsal lateral striatum (DLS) in Otsuka Long Evans Tokushima Fatty (OLETF) rats that lack CCK‐A receptors due to a spontaneous mutation. OLETF rats and normal Long Evans rats were treated with subcutaneous (s.c.) injections of saline or haloperidol (2 mg/kg). In situ hybridization was performed and zif268 mRNA expression was quantified. The haloperidol‐induced expression of zif268 mRNA was significantly decreased in the DLS (P < 0.01) and the NA shell (P < 0.05), but not in the NA core, in OLETF rats compared to LETO rats. These data suggest that CCK‐A receptor mechanisms may contribute to the therapeutic and the extrapyramidal motor effects associated with antipsychotic drug treatment. Synapse 43:134–138, 2002. © 2001 Wiley‐Liss, Inc.
Time window of autoreceptor‐mediated inhibition of limbic and striatal dopamine release
Authors: Phillips Paul E.M. , Hancock Pamela J. , Stamford Jonathan A. 
Published: August 2002

AbstractForebrain dopamine release is under the local control of D2 family (D2 and D3) autoreceptors. In this study, autoreceptor‐mediated modulation of forebrain dopamine release was investigated using amperometry in brain slices following local electrical stimulation. 350 μm‐thick slices of nucleus accumbens or dorsolateral neostriatum were prepared from male Wistar rats (150–200 g) and superfused with artificial cerebrospinal fluid at 32°C. Dopamine release was evoked by electrical pulses (0.1 ms, 10 mA) across bipolar tungsten stimulating electrodes and measured at carbon fibre microelectrodes using fixed potential amperometry (+300 mV vs. Ag/AgCl). Peak dopamine release on stimulation (single pulse) was 0.75 μM (neostriatum) and 1.37 μM (nucleus accumbens). Metoclopramide (1 μM) had no significant effect on DA efflux from a single pulse in either region. Using paired pulse stimuli, dopamine release on the second pulse varied according to the interval between the two pulses. At very long intervals (>20 sec), dopamine release was similar to that for the first pulse. At shorter intervals, dopamine efflux was attenuated. Metoclopramide had no effect on second pulse dopamine release when the pulse was applied at short (<0.1 sec) or long (>5.0 sec) intervals after the first. At intermediate intervals, metoclopramide significantly increased second pulse dopamine release. The peak dopamine autoreceptor effect occurred at ∼550 ms in neostriatum and ∼700 ms in nucleus accumbens. The onset time is due both to diffusion of dopamine from the release sites to the autoreceptors and receptor‐effector mechanisms. These findings may have implications for the local control of forebrain dopamine function in physiological and pathological states. Synapse 44:15–22, 2002. © 2002 Wiley‐Liss, Inc.
Measurement of dopamine transporter occupancy for multiple injections of cocaine using a single injection of [F‐18]FECNT
Authors: Votaw John R. , Howell Leonard L. , Martarello Laurent , Hoffman John M. , Kilts Clinton D. , Lindsey Kimberly P. , Goodman Mark M. 
Published: August 2002

AbstractThe fraction of transporters occupied following injection of specific inhibitors is an important parameter for defining and comparing the molecular mechanisms of different drugs. This work generalizes the reference tissue method to estimate dopamine transporter occupancy for two levels of cocaine administration using only a single injection of [18F]FECNT. The results are validated by comparison with literature values. Five rhesus monkeys were studied. On each animal, a baseline scan was collected following [18F]FECNT injection (phase a). At 120 min postinjection, 0.1 mg/kg cocaine was injected and the animal was scanned for 50 additional min (phase b). Then 1.0 mg/kg cocaine was injected and another 50‐min scan sequence was collected (phase c). Time–activity curves (encompassing all three phases) were generated for each animal from regions drawn over the putamen and cerebellum. The putamen curve was modeled using the cerebellum as the input function. Percent DAT occupancy following the cocaine injections was determined by comparing k3/k4 = Bmax/kD for the three phases. The 0.1 and 1.0 mg/kg cocaine doses occupied 53% ± 5% and 87% ± 5% of the transporters, respectively. The measured occupancies are consistent with literature values that maintain self‐administration in animals and produce a “high” in human subjects. This work demonstrates that a single injection of [18F]FECNT can be used to measure the effects of multiple cocaine challenges. Two advantages of this technique are: reduced variability in dose–response curves because the subject is his/her own control, and the 18F label allows evaluation of longer‐acting drugs. Synapse 44:203–210, 2002. © 2002 Wiley‐Liss, Inc.
Distribution of members of the PSD‐95 family of MAGUK proteins at the synaptic region of inner and outer hair cells of the guinea pig cochlea
Authors: Davies Caroline , Tingley Debora , Kachar Bechara , Wenthold Robert J. , Petralia Ronald S. 
Published: August 2002

AbstractPDZ‐domain containing proteins of the MAGUK (membrane‐associated guanylate kinase) family target, anchor, and cluster receptors and channels to subcellular sites. Among the MAGUK proteins, the members of the PSD‐95 family (MAGUKs: PSD‐95, PSD‐93, SAP‐97, and SAP‐102) target and anchor glutamate receptors to the synaptic terminals. Associations of glutamate receptors with MAGUKs have been described in the brain but not in the cochlea. In this study, RT‐PCR, immunofluorescence microscopy, and immunoelectron microscopy were used to investigate the presence and distribution of MAGUK proteins in the organ of Corti. The presence of the mRNA for PSD‐95, PSD‐93, SAP‐97, and SAP‐102 in the organ of Corti was confirmed by RT‐PCR. Immunocytochemistry using a “pan‐MAGUK” antibody, which recognizes all four MAGUK proteins, and selective antibodies against these proteins revealed that all four MAGUKs are present within the base of inner hair cells while all except SAP‐97 are found within the base of the outer hair cells. In addition, PSD‐93 and PSD‐95 are found in postsynaptic afferent terminals on inner hair cells, while postsynaptic afferent terminals on outer hair cells have PSD‐93. Synapse 40:258–268, 2001. © 2001 Wiley‐Liss, Inc.
Changes in hippocampal adenosine efflux, ATP levels, and synaptic transmission induced by increased temperature
Authors: Masino Susan A. , Latini Serena , Bordoni Francesca , Pedata Felicita , Dunwiddie Thomas V. 
Published: August 2002

AbstractPrevious studies have demonstrated that when the temperature of hippocampal brain slices is increased, there is a corresponding depression of synaptic potentials mediated by an increased activation of presynaptic adenosine A1 receptors. The present experiments demonstrate that when the temperature of hippocampal slices is raised from 32.5°C to either 38.5°C or 40.0°C there is a marked, temperature‐dependent increase in the efflux of endogenous adenosine and a corresponding decrease in excitatory synaptic responses. The increase in efflux is rapidly reversible on lowering the slice temperature and the temperature‐induced efflux is repeatable. Control experiments suggest that this increased efflux of adenosine is not the result of hypoxia or ischemia secondary to a temperature‐induced increase in the metabolic rate of the slice. The increase in adenosine efflux was not accompanied by any significant change in the ATP levels in the brain slice, whereas a hypoxic stimulus sufficient to produce a comparable depression of excitatory transmission produced an ∼75% decrease in ATP levels. These experiments indicate that changes in brain slice temperature can alter purine metabolism in such a way as to increase the adenosine concentration in the extracellular space, as well as adenosine efflux from hippocampal slices, in the absence of significant changes in ATP levels. Synapse 41:58–64, 2001. © 2001 Wiley‐Liss, Inc.
Effects of bilateral olfactory bulbectomy on N‐methyl‐D‐aspartate receptor function: Autoradiographic and behavioral studies in the rat
Authors: Robichaud Malika , Beauchemin Valérie , Lavoie Normand , Dennis Trevor , Debonnel Guy 
Published: August 2002

AbstractRat bilateral olfactory bulbectomy (OBX) serves as a useful model in the study of depression and the mechanisms of action of antidepressant treatments. Considering the evidence of NMDA receptors involvement in depression, the present study was undertaken in order to investigate the time‐course effects of OBX on the NMDA receptor function. Following bilateral olfactory bulbectomy, rats display an increase in locomotor activity and changes in other types of behavior in a novel environment. Autoradiographic experiments using the noncompetitive NMDA antagonist [125I]‐iodo‐MK‐801 as the labeling agent showed that this increase in behavioral activities corresponds to a decrease in [125I]‐iodo‐MK‐801 binding in a number of brain regions. In most regions, this reduction reached significance by the third week following OBX. However, in some cortical areas—a nucleus of the thalamus (AV) and one of the amygdala (LA)—this reduction was already significant in the first or second week following OBX and lasted throughout the 4 weeks of the study. We also compared the behavioral modifications induced by a challenge injection of MK‐801 (0.2 mg/kg i.p.) in OBX and sham‐operated rats. This challenge is known to induce hyperlocomotion and a number of stereotypies in naive rats. These effects were drastically reduced in OBX as compared to sham‐operated rats. These data are consistent with the above‐mentioned decrease in cerebral binding of MK‐801 to NMDA receptors. Synapse 42:95–103, 2001. © 2001 Wiley‐Liss, Inc.
Evaluation of [4‐O‐methyl‐11C]KW‐6002 as a potential PET ligand for mapping central adenosine A2A receptors in rats
Authors: Hirani E. , Gillies J. , Karasawa A. , Shimada J. , Kase H. , Opacka‐Juffry J. , Osman S. , Luthra S.K. , Hume S.P. , Brooks D.J. 
Published: August 2002

AbstractKW‐6002, a xanthine‐based adenosine A2A antagonist, was labelled with the positron emitter carbon‐11 by O‐methylation of its precursor, KF23325, using [11C]iodomethane and was evaluated in rats as a putative in vivo radioligand for positron emission tomography (PET). Following intravenous injection of [11C]KW‐6002, radioactivity was measured in blood, plasma, peripheral tissues, and in discrete brain tissues over a 2‐h time period commensurate with PET scanning. In brain, [11C]KW‐6002 showed highest retention in striata, with evidence of saturable binding, and lowest retention in frontal cortex (a tissue low in adenosine A2A receptors). PET scanning with [11C]KW‐6002 demonstrated a specific signal in the striata which could be described using compartmental modelling. Specific binding was, however, also detected in extrastriatal regions, including brain areas reported to have low adenosine A2A receptor density. Blocking studies with the A1 selective antagonist KF15372 and the non xanthine‐type A2A antagonist ZM 241385 failed to elucidate the nature of this binding. Thus, although [11C]KW‐6002 shows some potential for development as a PET ligand for quantifying striatal adenosine A2A receptor function, its in vivo selectivity requires further investigation. Synapse 42:164–176, 2001. © 2001 Wiley‐Liss, Inc.
Changes in neuronal activation with increasing attention demand in healthy volunteers: An fMRI study
Authors: Adler Caleb M. , Sax Kenji W. , Holland Scott K. , Schmithorst Vince , Rosenberg Lee , Strakowski Stephen M. 
Published: August 2002

AbstractSeveral lines of evidence suggest that structures involved in mediating attention differentially respond to increasing processing demand. Investigation of differences in neuronal activation, however, has been complicated by methodological inconsistencies and concomitant discrepancies in degree of difficulty and subject effort between disparate tasks. In this study, we utilized fMRI to compare neural activation patterns associated with two related attention tasks associated with different degrees of processing load while controlling for degree of performance difficulty. Healthy volunteers performed two continuous performance tasks, utilizing an identical pairs paradigm (CPT‐IP) and a matched simple number recognition paradigm with degraded stimuli (CPT‐DS) during a single fMRI scan. Degree of stimulus resolution degradation in the latter CPT was designed to equalize degree of performance difficulty between the two tasks. CPT‐IP and CPT‐DS were both associated with activation of frontal, limbic, subcortical, and sensory integratory structures. CPT‐IP administration was associated with significantly greater activation of left dorsolateral prefrontal cortex, bilateral posterior temporal cortex, bilateral putamen, and thalamus. This study demonstrates both that differing attention tasks are associated with a high degree of functional overlap and that increasing processing demand is associated with increased activation of specific portions of attentional networks. Synapse 42:266–272, 2001. © 2001 Wiley‐Liss, Inc.
Realizing the benefits of the CMMISM with the CeBASE method
Authors: Boehm Barry , Port Daniel , Basili Victor 
Published: August 2002

AbstractFuture systems will be increasingly software‐intensive, but the type of software development they will need is not well covered by current development and maturity models such as the waterfall model and Software Capability Maturity Model® (CMM®). Future development of software‐intensive systems will need situation‐specific balancing of discipline and flexibility to address such issues as COTS, open source, distribution, mobility rapid change, agents, collaboration support, and simultaneous achievement of rapid development and high dependability. This article shows how the CMMISM's integration of modern systems engineering, software engineering, and integrated process and product development concepts provides a framework for redressing the shortfalls of the Software CMM®, and for enabling projects and organizations to achieve the right balance of discipline and flexibility for their particular situations. But the CMMISM has shortfalls of its own. It provides little guidance on how to define and execute specific processes for a specific project or organization. The article summarizes various process model generators for software intensive systems such as the spiral, the Rational Unified Process (RUP), MBASE, and the CeBASE Method. It concludes that the CeBASE Method best covers the full range of concerns in the CMMISM, resolves its practice‐focus shortfalls, and covers additional best practices not in the CMMISM, such as business case analysis, requirements prioritization, and evolution requirements. © 2002 John Wiley & Sons, Inc. Syst Eng 5: 73–88, 2002; DOI 10.1002/sys.10016
Reproductive toxicology: The science today
Authors: Neubert Diether 
Published: August 2002

AbstractReproductive toxicology is concerned with chemical or physical agents interfering with fertility in both gender. Adverse effects may be induced directly, especially in adult males by damaging the semen producing epithelium (e.g., DBCP), or indirectly, predominantly by interfering with sex hormonal homeostasis. Many critical events must occur during well‐defined periods of prenatal and early postnatal development of the reproductive system. Most of such differentiation processes, several of which in the male critically depend on inducing influences of androgens, cannot take place at later stages, and lack of “imprinting” will result in irreversible defects or dysfunctions. These processes might be disturbed by interfering agents (e.g., by anti‐androgens: feminization), provided that the exposure is high enough. Several of the processes known to be essential for male development can also be altered in females by exposure to a large excess of androgens (masculinization). Essential processes required for normal male development include: 1) androgen‐dependent differentiation of the male phenotype during late embryonic development, 2) differentiation of the male secondary sex organs during the fetal period, 3) formation of a fixed number of Sertoli cells during the perinatal period, 4) imprinting of male sexual behavior in defined brain areas during the perinatal period, 5) imprinting of the pulsatile GnRH regulation of hypophysial hormone formation in both gender via the hypothalamico‐hypophysial axis, and 6) differentiation of the male organism during puberty. Many effects on fertility can be induced on the adult organism. Besides a direct action on the receptors, inhibition of the feed back mechanism that guarantees sex hormonal homeostasis is another mode of action. Many synthetic steroid compounds exhibit effects on more than one receptor, thus causing a complex situation. This must also be taken into account when analyzing possible effects of “ecohormones.” Adverse hormonal actions are well established from experience in clinical and experimental medicine, using either natural or synthetic sex hormones, or enzyme inhibitors. Possible effects of “environmental” agents either mimicking or inhibiting sex hormonal actions are less well studied in clinical trials. Because of considerable species differences in hormonal effects, especially in pharmacokinetics, data of animal studies are of limited predictive value for extrapolations in preventive hazard minimization (but may be useful for revealing possible mechanisms of action). Data of in‐vitro studies are even less suitable for extrapolations. It may be doubted that exposure of the general population to “ecohormones” or “xenohormones” is sufficient to induce clear‐cut clinical effects. Adverse effects induced by, e.g., greatly unbalanced diets or after accidental overdoses cannot be excluded. Teratogenesis Carcinog. Mutagen. 22:159–174, 2002. © 2002 Wiley‐Liss, Inc.
Mutation analysis of left‐right axis determining genes in NOD and ICR, strains susceptible to maternal diabetes
Authors: Maeyama Katsuhiro , Kosaki Rika , Yoshihashi Hiroshi , Casey Brett , Kosaki Kenjiro 
Published: August 2002

AbstractBackgroundGenetic background of the fetus contributes to the pathogenesis of congenital malformation after teratogen exposure. Such contribution is illustrated in left‐right axis malformations observed in the F1 offspring of nonobese diabetic (NOD) mouse dams and sires from different strains. When sires of the NOD, ICR, or C57BL/6J were mated with NOD dams, incidence varied depending on the fetal genotype, with 65% in NOD × NOD, 24% in NOD × ICR, and 7% in NOD × C57BL/6J.MethodsAs a first step in elucidating the molecular basis of the interstrain differences in susceptibility to situs defects, we compared genomic sequences of six genes HNF3beta, Acvr2b, Nodal, ZIC3, Lefty1, and Smad2, which are involved in the normal development of left‐right axis among NOD, ICR, and C57BL/6J strains.ResultsThe outbred strain ICR had 1) a 0.2‐kb insertion in the putative promoter region of the isoform E of HNF3beta together with a G to A change that could create a potential splice acceptor in the exon 3 of HNF3beta (gene frequency P = 0.36), 2) five single base substitutions within the 5′ controlling element and a proline to serine substitution (P2S) of Lefty1 (P = 0.77), and 3) a tyrosine to histidine substitution within the prodomain of Nodal (P = 0.48). The inbred strain NOD had the same G to A change as ICR and a three‐base deletion in the putative promoter of isoform E of HNF3β.ConclusionsWe suggest that sequence variations in HNF3β, Lefty1, and Nodal might account, in part, for the interstrain differences in susceptibility to situs abnormalities among the offspring of diabetic dams. Teratology 63:119–126, 2001. © 2001 Wiley‐Liss, Inc.
Morocco
Authors: Gray Kenneth R. , Amine Lyn S. 
Published: August 2002

AbstractIn 1999 a new king came to the throne in Morocco, Mohamed VI. This event is proving to be a watershed in the
economic and political history of Morocco as new policies, initiatives, and goals are being developed and
implemented. This article provides background information on the business environment of Morocco regarding
history, politics, culture, the economy, regulations and laws, human resource management, and marketing
practices. Detailed insights are presented to enable foreign investors and business people to understand
inportant aspects of doing business in Morocco. Finally we present our expectatons for the future of Morocco and
its trading partners. © 2002 Wiley Periodicals, Inc.
Research Note: Strategic Combinations and Their Evolution in the Global Marketplace
Authors: Powers Thomas L. , Jones Rachel Collins 
Published: August 2002

AbstractThe global marketplace of the twenty‐first century will contain many new competitors formed from the
mergers and alliances that are currently taking place. This article demonstrates how the globalization process
is in reality an extension of a pattern that has existed since the Industrial Revolution, that today continues
to create competitive advantage. Significant managerial implications are given based on this discussion. ©
2001 John Wiley & Sons, Inc.
Apoptotic effect of cyanobacterial extract on rat hepatocytes and human lymphocytes
Authors: Mankiewicz Joanna , Tarczynska Malgorzata , Fladmark Kari Espolin , Doskeland Stein Ove , Walter Zofia , Zalewski Maciej 
Published: August 2002

AbstractToxic cyanobacterial blooms are an increasing problem in Poland. The production of cyanobacterial toxins and their presence in drinking and recreational waters represent a growing danger to human and animal health. This is connected with the increase of cyanobacterial biomass caused by excessive eutrophication of the water ecosystem. There is evidence that cyanobacterial hepatotoxins can act as a potent promoter of primary liver cancer. The apoptotic effect of microcystins in Polish cyanobacterial bloom samples on rat hepatocytes and human lymphocytes was observed using light and fluorescence microscopy, flow cytometry, and electrophoretic analysis. The incubation time needed to observe the first morphological apoptotic changes in hepatocytes was approximately 30 min; however, the characteristic biochemical changes in DNA were not observed even after 120 min. In lymphocyte cultures the morphological changes characteristic for apoptosis were observed after 24 h of incubation and a 48‐h incubation was found to be optimal for analysis of internucleosomal DNA fragmentation, which is one of the main biochemical hallmarks of programmed cell death. These cells are an easily isolated and inexpensive material for medical diagnostics. Therefore the apoptotic changes, together with the clastogenic effect seen in lymphocyte cultures, are proposed as a future analytical method for these toxins. © 2001 John Wiley & Sons, Inc. Environ Toxicol 16: 225–233, 2001