bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of the sensitivities of distinct gastric cancer cells to parvovirus H‐1 induced cytotoxicity
Authors: RAN Zhi Hua , LIU Jiong , FENG Ying , ZOU Jian , XIAO Shu Dong
Published: July 2004

OBJECTIVE:  To investigate the sensitivities of distinct gastric cancer cells to parvovirus H‐1 induced cytotoxicity and the possible mechanism(s).

METHODS:  There were six distinct differentiated gastric cancer cell lines: HGC27 (undifferentiated), BGC823 (undifferentiated), MKN45 (poorly differentiated), AGS (poorly differentiated), SGC7901 (moderately differentiated) and MKN28 (well differentiated). The cell cycle distributions were measured by flow cytometry and the differential sensitivities of the six distinct gastric cancer cells after H‐1 virus infection were detected by MTT assay. RT‐PCR was used to detect viral NS1 gene expression in all six gastric cancer cell lines.

RESULTS:  The S phase ratios of HGC27, BGC823, MKN45, AGS, SGC7901 and MKN28 were 24.72%, 30.15%, 27.10%, 29.03%, 31.82% and 33.73%, respectively. HGC27 cells were sensitive to H‐1 virus induced cytotoxicity, followed by SGC7901 cells. MKN45 and AGS cells were moderately sensitive and MKN28 cells were insensitive. However, BGC823 cells were resistant to H‐1 virus induced cytotoxicity. The expressions of viral NS1 were higher in HGC27, BGC823, MKN45 and SGC7901 cells, and lower in AGS and MKN28 cells.

CONCLUSIONS:  The sensitivities of the distinct gastric cancer cells to H‐1 virus induced cytotoxicity were markedly different. In general, the poorly differentiated cells showed an enhanced sensitivity to H‐1 virus attack compared with well‐differentiated ones. The enhanced sensitivity of poorly versus well‐differentiated gastric cancer cells to H‐1 virus is related in part to the enhanced capacity of the former for NS1 protein production and accumulation. The undifferentiated BGC823 cells were resistant to H‐1 virus triggered cytotoxicity. It may further verify that not all tumor cells are sensitive to H‐1 virus lytic effects.
Effects and mechanism of the selective COX‐2 inhibitor, celecoxib, on rat colitis induced by trinitrobenzene sulfonic acid
Authors: ZHANG Ling , LU Yu Min , DONG Xiu Yun
Published: July 2004

OBJECTIVE:  To investigate the action of celecoxib (a selective COX‐2 inhibitor) in a rat model of colitis induced by trinitrobenzene sulfonic acid (TNBS).

METHODS:  Rats were randomized into four groups. Colitis was induced in groups 1 and 2 by intracolonic administration of TNBS (25 mg/mL) in 50% ethanol (0.25 mL). The rats in group 1 received oral celecoxib (1.25 mg/kg) and those in group 2 received distilled water (1 mL/0.3 kg), beginning 3 h before induction of colitis and continuing twice daily thereafter for up to 7 days. The rats in group 4 received oral celecoxib (1.25 mg/kg) twice daily for 7 days and those in group 3 were healthy controls. All rats that survived 7 days were killed and both the severity of colonic mucosal damage and the prostaglandin E2 (PGE2) concentrations of the colonic mucosa were assessed.

RESULTS:  The colonic mucosal damage scores for groups 1 and 2 were 11.15 ± 3.30 and 8.50 ± 2.82, respectively, both of which were significantly higher than the score for the healthy controls (0.62 ± 0.09; P < 0.01, P < 0.01). The score of group 1 was significantly higher than that of group 2 (P < 0.05). No difference was found between the scores of groups 3 and 4. The mucosal concentrations of PGE2 in groups 1 and 2 were 12.00 ± 4.33 pg/µg and 17.20 ± 9.62 pg/µg, respectively, both of which were significantly higher than the concentration in the healthy controls (6.02 ± 3.39 pg/µg; P < 0.05, both). The PGE2 concentration of group 1 was decreased significantly compared with that of group 2 (P < 0.05). No difference was found between groups 3 and 4.

CONCLUSION:  The results suggest that treatment with celecoxib exacerbates inflammation‐associated colonic injury in experimental colitis induced by TNBS. This preliminary study shows that the mechanism is related to suppression by the COX‐2 inhibitor of the PG derived from COX‐2, but further study is needed to identify if there are other related mechanisms.
Effect of short‐chain fatty acids on the proliferation and differentiation of the human colonic adenocarcinoma cell line Caco‐2
Authors: FU Hong , SHI Ying Qiang , MO Shan Jin
Published: July 2004

OBJECTIVE:  Short‐chain fatty acids (SCFA) in the colon may maintain colonocyte differentiation and oppose carcinogenesis. The purpose of this study was to investigate the effects of three SCFA, butyrate, propionate and acetate, on the differentiation, proliferation, and matrix interactions of the Caco‐2 human colonic adenocarcinoma cell line.

METHODS:  Differentiation was assessed by brush border enzyme expression and the doubling time (proliferation) was calculated directly from serial cell counts and by the logarithmic transformation method. Cell motility (migration) was quantitated by the expansion of a confluent Caco‐2 monolayer (after release from a constraining fence) across bacteriologic plastic dishes precoated with saturating concentrations of type I collagen. Results were expressed as mean ± SE and were analyzed by anova and Bonferroni's modified t‐test.

RESULTS:  All three SCFA studied altered the Caco‐2 phenotype. Treatment with 10 mmol SCFA significantly prolonged the cell doubling time, promoted brush border enzyme expression (cathepsin C), and inhibited the motility of the Caco‐2 cells.

CONCLUSIONS:  Butyrate, propionate and acetate inhibited the proliferation and motility of a well‐differentiated human colonic cancer cell line while promoting the expression of the differentiation marker, cathepsin C. Thus the SCFA produced by bacterial fermentation of dietary fiber may exert a protective effect against the development of colon cancer.
Assessing heterogeneity in meta‐analyses of Helicobacter pylori infection‐related clinical studies: a critical appraisal
Authors: HUANG Jia Qing , ZHENG Ge Fan , IRVINE E Jan , KARLBERG Johan
Published: July 2004

OBJECTIVE:  To critically assess the meta‐analyses of Helicobacter pylori infection‐related clinical studies, particularly the handling of between‐study heterogeneity.

METHODS:  A qualitative, all‐language, systematic literature search was performed in Medline, PubMed, BioMed Central and Embase up to February 2003, supplemented by a manual search of major relevant journals. Assessment was according to modified criteria for literature searching, eligibility criteria, validity assessment, data extraction and presentation. Five parameters were used to assess the quality of the meta‐analyses in handling between‐study heterogeneity.

RESULTS:  Of 84 potentially relevant citations, 47 were systematic reviews and of them 38 were meta‐analyses. Of these 38 studies, 15 (39.5%) had conducted a literature search of multiple databases and 34 (89.5%) had conducted a supplementary manual search. The eligibility criteria were clearly presented in 81.6% of studies, but the quality of the primary studies was assessed in only 26.3%. The process and strategy for data extraction was reported in 57.9% of all studies; 19 (50%) studies planned statistical tests of between‐study homogeneity and the results were reported in 18, but the level of statistical significance was reported in only 11 (57.9%). The selection of and justification for a statistical model was presented in 39.5% and 26.3% of studies, respectively. Among the 11 meta‐analyses in which statistical between‐study heterogeneity was reported, 54.5% ignored the statistical findings and proceeded to pool the study results. The implications of between‐study heterogeneity were discussed in only 8 studies.

CONCLUSIONS:  Many methodological flaws were identified in the meta‐analyses of H. pylori‐related clinical studies, particularly for assessing, reporting and interpreting between‐study heterogeneity. This warrants consistent and urgent adherence by reviewers and journal editors to the methodological guidelines for meta‐analyses.
Decrease of Hsp25 protein expression precedes degeneration of motoneurons in ALS‐SOD1 mice
Authors: Maatkamp Arjen , Vlug Angela , Haasdijk Elize , Troost Dirk , French Pim J. , Jaarsma Dick
Published: July 2004

We have investigated the expression of Hsp25, a heat shock protein constitutively expressed in motoneurons, in amyotrophic lateral sclerosis (ALS) mice that express G93A mutant SOD1 (G93A mice). Immunocytochemistry and Western blotting showed that a decrease of Hsp25 protein expression occurred in motoneurons of G93A mice prior to the onset of motoneuron death and muscle weakness. This decrease in Hsp25 expression also preceded the appearance of SOD1 aggregates as identified by cellulose acetate filtration and Western blot analysis. In contrast to Hsp25 protein levels, Hsp25 mRNA as determined by in situ hybridization and RT‐PCR, remained unchanged. This suggests that the decrease in Hsp25 protein levels occurs post‐transcriptionally. In view of the cytoprotective properties of Hsp25 and the temporal relationship between decreased Hsp25 expression and the onset of motoneuron death, it is feasible that reduced Hsp25 concentration contributes to the degeneration of motoneurons in G93A mice. These data are consistent with the idea that mutant SOD1 may reduce the availability of the protein quality control machinery in motoneurons.
Auxiliary subunit regulation of high‐voltage activated calcium channels expressed in mammalian cells
Authors: Yasuda Takahiro , Chen Lina , Barr Wendy , McRory John E. , Lewis Richard J. , Adams David J. , Zamponi Gerald W.
Published: July 2004

The effects of auxiliary calcium channel subunits on the expression and functional properties of high‐voltage activated (HVA) calcium channels have been studied extensively in the Xenopus oocyte expression system, but are less completely characterized in a mammalian cellular environment. Here, we provide the first systematic analysis of the effects of calcium channel β and α2–δ subunits on expression levels and biophysical properties of three different types (Cav1.2, Cav2.1 and Cav2.3) of HVA calcium channels expressed in tsA‐201 cells. Our data show that Cav1.2 and Cav2.3 channels yield significant barium current in the absence of any auxiliary subunits. Although calcium channel β subunits were in principle capable of increasing whole cell conductance, this effect was dependent on the type of calcium channel α1 subunit, and β3 subunits altogether failed to enhance current amplitude irrespective of channel subtype. Moreover, the α2–δ subunit alone is capable of increasing current amplitude of each channel type examined, and at least for members of the Cav2 channel family, appears to act synergistically with β subunits. In general agreement with previous studies, channel activation and inactivation gating was regulated both by β and by α2–δ subunits. However, whereas pronounced regulation of inactivation characteristics was seen with the majority of the auxiliary subunits, effects on voltage dependence of activation were only small (< 5 mV). Overall, through a systematic approach, we have elucidated a previously underestimated role of the α2–δ1 subunit with regard to current enhancement and kinetics. Moreover, the effects of each auxiliary subunit on whole cell conductance and channel gating appear to be specifically tailored to subsets of calcium channel subtypes.
Oestrogen‐deficient female aromatase knockout (ArKO) mice exhibit ‘depressive‐like’ symptomatology
Authors: Dalla C. , Antoniou K. , Papadopoulou‐Daifoti Z. , Balthazart J. , Bakker J.
Published: July 2004

We recently found that female aromatase knockout (ArKO) mice that are deficient in oestradiol due to a targeted mutation in the aromatase gene show deficits in sexual behaviour that cannot be corrected by adult treatment with oestrogens. We determined here whether these impairments are associated with changes in general levels of activity, anxiety or ‘depressive‐like’ symptomatology due to chronic oestrogen deficiency. We also compared the neurochemical profile of ArKO and wild‐type (WT) females, as oestrogens have been shown to modulate dopaminergic, serotonergic and noradrenergic brain activities. ArKO females did not differ from WT in spontaneous motor activity, exploration or anxiety. These findings are in line with the absence of major neurochemical alterations in hypothalamus, prefrontal cortex or striatum, which are involved in the expression of these behaviours. By contrast, ArKO females displayed decreased active behaviours, such as struggling and swimming, and increased passive behaviours, such as floating, in repeated sessions of the forced swim test, indicating that these females exhibit ‘depressive‐like’ symptoms. Adult treatment with oestradiol did not reverse the behavioural deficits observed in the forced swim test, suggesting that they may be due to the absence of oestradiol during development. Accordingly, an increased serotonergic activity was observed in the hippocampus of ArKO females compared with WT, which was also not reversed by adult oestradiol treatment. The possible organizational role of oestradiol on the hippocampal serotonergic system and the ‘depressive‐like’ profile of ArKO females provide new insights into the pathophysiology of depression and the increased vulnerability of women to depression.
Sympathetic activation triggers endogenous opioid release and analgesia within peripheral inflamed tissue
Authors: Binder Waltraud , Mousa Shaaban A. , Sitte Nicolle , Kaiser Myriam , Stein Christoph , Schäfer Michael
Published: July 2004

Stress induces analgesia by mechanisms within and outside the brain. Here we show that the sympathetic nervous system is an essential trigger of intrinsic opioid analgesia within peripheral injured tissue. Noradrenaline, injected directly into inflamed hind paws of male Wistar rats, produced dose‐dependent antinociception, reversible by α1‐, α2‐ and β2‐antagonists. α1‐, α2‐ and β2‐adrenergic receptors were demonstrated on β‐endorphin‐containing immune cells and noradrenaline induced adrenergic receptor‐specific release of β‐endorphin from immune cell suspensions. This antinociceptive effect of noradrenaline was reversed by µ‐ and δ‐opioid antagonists as well as by anti‐β‐endorphin. Stress‐induced peripheral analgesia was abolished by chemical sympathectomy and by adrenergic antagonists. These findings indicate that sympathetic neuron‐derived noradrenaline stimulates adrenergic receptors on inflammatory cells to release β‐endorphin, which induces analgesia via activation of peripheral opioid receptors.
Experimental evidence and modeling studies support a synchronizing role for electrical coupling in the cat thalamic reticular neurons in vivo
Authors: Fuentealba Pablo , Crochet Sylvain , Timofeev Igor , Bazhenov Maxim , Sejnowski Terrence J. , Steriade Mircea
Published: July 2004

Thalamic reticular (RE) neurons are crucially implicated in brain rhythms. Here, we report that RE neurons of adult cats, recorded and stained intracellularly in vivo, displayed spontaneously occurring spikelets, which are characteristic of central neurons that are coupled electrotonically via gap junctions. Spikelets occurred spontaneously during spindles, an oscillation in which RE neurons play a leading role, as well as during interspindle lulls. They were significantly different from excitatory postsynaptic potentials and also distinct from fast prepotentials that are presumably dendritic spikes generated synaptically. Spikelets were strongly reduced by halothane, a blocker of gap junctions. Multi‐site extracellular recordings performed before, during and after administration of halothane demonstrated a role for electrical coupling in the synchronization of spindling activity within the RE nucleus. Finally, computational models of RE neurons predicted that gap junctions between these neurons could mediate the spread of low‐frequency activity at great distances. These experimental and modeling data suggest that electrotonic coupling within the RE nucleus plays an important role in the generation and synchronization of low‐frequency (spindling) activities in the thalamus.
The basolateral complex of the amygdala mediates the modulation of intracranial self‐stimulation threshold by drug‐associated cues
Authors: Hayes Robert J. , Gardner Eliot L.
Published: July 2004

Learning and memory appear to be critical aspects of drug abuse; presumably playing an especially important role in craving and relapse. Thus, understanding the interaction of learning‐ and memory‐related brain areas with the classical reward circuitry is of importance. Toward this goal, the effect of drug‐associated contextual cues on intracranial self‐stimulation (ICSS) behaviour was assessed in rats. We used a method that allows the establishment of baseline behaviour, the pairing of drug exposure with unique cues, and testing the effect of cue exposure within the same apparatus. ICSS thresholds were decreased by morphine (5 mg/kg, i.p.) or cocaine (10 mg/kg, i.p.) during five days of paired drug‐cue training sessions. Subsequent presentation of the drug‐associated cues decreased thresholds in the absence of drug. Cues associated with saline had no effect. These results suggest a Pavlovian conditioning phenomenon in which the functioning of brain reward circuitry is modulated by drug‐associated cues. In a second experiment, we tested the hypothesis that the mechanism by which conditioning affects ICSS thresholds may include the basolateral complex of the amygdala (BLC) due to its known role in conditioning and anatomical linkage with classical reward circuitry. Lesions of the BLC abolished the ability of cocaine‐associated cues to lower ICSS threshold. Lesions did not alter response capability or the unconditioned effect of cocaine. We conclude that the BLC is necessary for cues associated with previous drug exposure to modulate activity within or downstream from the classical reward circuitry of the medial forebrain bundle.
Context‐independent directional cue learning by hippocampal place cells
Authors: Chakraborty Subhojit , Anderson Michael I. , Chaudhry Amir M. , Mumford Julie C. , Jeffery Kathryn J.
Published: July 2004

In a symmetrical environment possessing no other polarizing visual cues, the spatially localized firing of hippocampal place cells can be primarily orientated by a reliable distal visual stimulus, such as a white cue card. However, if such a directional cue is made unreliable by being frequently moved in full view of the rat, the rat's internal sense of direction comes, over the course of a few days, to control the orientation of place fields instead. We investigated whether this simple form of ‘cue‐instability’ learning would transfer to a new context, in which the firing patterns of the place cells become reorganized and in which a new spatial representation is thus active. We found that after cue‐instability learning, the ‘remapped’ place field representation in the new environment was also orientated by the internal sense of direction of the rat rather than by the cue card, showing that the cue learning generalized from one context (and hence spatial representation) to another. This contrasts with another kind of place cell learning, in which the cells can acquire the ability to discriminate two spatial locations in one context but do not transfer this discrimination to a new context. We discuss the different effects of context changes on learned place cell activity in terms of the possible architecture of the inputs to place cells.
Phenotypic expression of the targeted null‐mutation in the dopamine transporter gene varies as a function of the genetic background
Authors: Morice Elise , Denis Cécile , Giros Bruno , Nosten‐Bertrand Marika
Published: July 2004

The dopamine transporter (DAT) plays a critical role in calibrating the duration and intensity of dopamine (DA) neurotransmission. Mice in which the DAT gene has been genetically deleted exhibit constitutively high levels of extrasynaptic DA and spontaneous hyperactivity. Numerous studies have characterized the adaptive molecular, physiological, and behavioural consequences of abnormal DA neurotransmission in these mice. In order to determine the genetic background contribution to these phenotypes, the DAT mutation was transferred on C57BL/6JOrl (B6) or DBA/2JOrl (D2) inbred backgrounds for more than ten generations of back‐crossing to derive three B6‐, D2‐, and B6xD2(F1)‐DAT strains. We observed that the genetic background dramatically affects phenotypes previously reported on DAT knockout (KO) mice. Depending on the genetic background, it was possible to restore survival, growth rate and ability to lactate. Interactions with the genetic background were found to modulate both quantitative and qualitative patterns of novelty‐driven spontaneous hyperactivity. The paradoxical calming effect of cocaine was observed for all DAT‐KO mice. However, the genetic background influenced individual threshold responses to both locomotor and rewarding effects of cocaine. These findings reveal the extent of phenotypic variation associated with the DAT mutation. They also provide concrete arguments against the assumption that the normal function of a gene can be inferred directly from its mutant phenotype.
Induction of pseudo‐periodic oscillation in voltage‐gated sodium channel properties is dependent on the duration of prolonged depolarization
Authors: Majumdar Sriparna , Foster Grant , Sikdar Sujit K.
Published: July 2004

The neuronal voltage‐gated sodium channels play a vital role in the action potential waveform shaping and propagation. Here, we report the effects of prolonged depolarization (1–160 s) on the detailed kinetics of activation, fast inactivation and recovery from slow inactivation in the rNav1.2a voltage‐gated sodium channel α‐subunit expressed in Chinese hamster ovary (CHO) cells. Wavelet analysis revealed that the duration and amplitude of a prolonged sustained depolarization altered all the steady state and kinetic parameters of the channel in a pseudo‐oscillatory fashion with time‐variable period and amplitude, often superimposed on a linear trend. The half steady state activation potential showed a reversible depolarizing shift of 5–10 mV with duration of prolonged depolarization, while half steady state inactivation potential showed a hyperpolarizing shift of 43–55 mV. The time periods for most of the parameters relating to activation and fast and slow inactivation, lie close to 28–30 s, suggesting coupling of these kinetic processes through an oscillatory mechanism. Co‐expression of the β1‐subunit affected the time periods of oscillation (close to 22 s for α + β1) in steady state activation parameters. Application of a pulse protocol that mimicked paroxysmal depolarizing shift (PDS), a kind of depolarization seen in epileptic discharges, instead of a sustained depolarization, also caused oscillatory behaviour in the rNav1.2a α‐subunit. This inherent pseudo‐oscillatory mechanism may regulate excitability of the neurons, account for the epileptic discharges and subthreshold membrane potential oscillation and offer a molecular memory mechanism intrinsic to the neurons, independent of synaptic plasticity.
Does amygdaloid corticotropin‐releasing hormone (CRH) mediate anxiety‐like behaviors? Dissociation of anxiogenic effects and CRH release
Authors: Merali Z. , Khan S. , Michaud D. S. , Shippy S. A. , Anisman H.
Published: July 2004

The brain corticotropin‐releasing hormone (CRH) circuits are activated by stressful stimuli, contributing to behavioral and emotional responses. The present study assessed anxiety‐like responses and in vivo neurochemical alterations at the central nucleus of the amygdala (CeA) evoked by exposure to an unfamiliar (anxiogenic) environment. Also, the impact of anxiolytic treatments and those that affect CRH were assessed in this paradigm. Novel environment (new cage) markedly suppressed ingestion of a palatable snack. This effect was dose‐dependently antagonized by diazepam and was utilized as an index of anxiety in the rodent. Although exposure to a novel environment also stimulated the in vivo release of CRH and glutamate at the CeA, various CRH antagonists (e.g. αh‐CRH, Cα‐MeCRH, CP‐154,526, antisauvagine‐30, preproTRH178‐199) did not attenuate the stressor‐elicited behavioral suppression, although Cα‐MeCRH was found to attenuate the freezing response elicited by contextual stimuli that were associated with previously administered footshock. Moreover, central infusion of CRH failed to suppress snack consumption in the home cage. Although diazepam had potent anxiolytic effects in this paradigm, this treatment did not prevent the stressor‐associated release of CRH and glutamate at the CeA. Thus, while neural circuits involving CRH and/or glutamatergic receptors at the CeA may be activated by an unfamiliar environment, the data challenge the view that activation of these receptors is necessary for the expression of anxiety‐like behavioral responses. Rather than provoking anxiety, these systems might serve to draw attention to events or cues of biological significance, including those posing a threat to survival.
Interleukin‐1β modulates state‐dependent discharge activity of preoptic area and basal forebrain neurons: role in sleep regulation
Authors: Alam Md. Noor , McGinty Dennis , Bashir Tariq , Kumar Sunil , Imeri Luca , Opp Mark R. , Szymusiak Ronald
Published: July 2004

Interleukin‐1β (IL‐1) is a pro‐inflammatory cytokine that has been implicated in the regulation of nonrapid eye movement (nonREM) sleep. IL‐1, IL‐1 receptors and the IL‐1 receptor antagonist (ra) are present normally in discrete brain regions, including the preoptic area (POA) of the hypothalamus and the adjoining magnocellular basal forebrain (BF). The POA/BF have been implicated in the regulation of sleep–wakefulness. We hypothesized that IL‐1 promotes nonREM sleep, in part by altering the state‐dependent discharge activity of POA/BF neurons. We recorded the sleep–wake discharge profiles of 83 neurons in the lateral POA/BF and assessed the effects of IL‐1, IL‐1ra, and IL‐ra + IL‐1 delivered through a microdialysis probe on state‐dependent neuronal discharge activity. IL‐1 decreased the discharge rate of POA/BF neurons as a group (n = 55) but wake‐related and sleep‐related neurons responded differently. IL‐1 significantly decreased the discharge rate of wake‐related neurons. Of 24 wake‐related neurons studied, 19 (79%) neurons exhibited a greater than 20% change in their discharge in the presence of IL‐1 during waking. IL‐1 suppressed the discharge activity of 18 of 19 responsive neurons. Of 13 sleep‐related neurons studied, IL‐1 increased the discharge activity of five and suppressed the discharge activity of four neurons. IL‐1ra increased the discharge activity of four of nine neurons and significantly attenuated IL‐1‐induced effects on neuronal activity of POA/BF neurons (n = 19). These results suggest that the sleep‐promoting effects of IL‐1 may be mediated, in part, via the suppression of wake‐related neurons and the activation of a subpopulation of sleep‐related neurons in the POA/BF.
Increased expression of Nogo‐A in hippocampal neurons of patients with temporal lobe epilepsy
Authors: Bandtlow Christine E. , Dlaska Margit , Pirker Susanne , Czech Thomas , Baumgartner Christoph , Sperk Günther
Published: July 2004

Mesial temporal lobe epilepsy (TLE) is associated with pronounced anatomical and biochemical changes in the hippocampal formation including extensive neurodegeneration, reorganization of mossy fibres and sprouting of interneurons. Although the anatomical features and some of the physiological consequences of hippocampal remodeling have been well documented, the molecular mechanisms underlying the profound and orientated outgrowth of hippocampal neurons in TLE are not yet understood. The reticulon protein Nogo‐A has been associated with an inhibitory action on axon growth and plasticity. Using immunohistochemistry and in situ hybridization, we investigated the expression of Nogo‐A in specimens obtained at surgery from patients with TLE compared with those obtained from autopsy controls. In control specimens, Nogo‐A immunoreactivity and mRNA were mainly confined to oligodendrocytes. Only ≈ 40% of the specimens revealed low expression of Nogo‐A mRNA in neurons. In contrast, in TLE patients with and without Ammon's horn sclerosis, Nogo‐A mRNA and immunoreactivity were markedly up‐regulated in most neurons (3.6‐ and 4.4‐fold increases in Nogo‐A mRNA in granule cells of sclerotic and nonsclerotic specimens) and their processes throughout the hippocampal formation. Similar elevations in Nogo‐A mRNA and protein levels were determined by quantitative RT‐PCR and Western blotting. Since Nogo‐A expression was also up‐regulated in specimens without hippocampal sclerosis, it may be induced by seizures prior to progressing neurodegeneration.
Contrasting effects of dopamine and glutamate receptor antagonist injection in the nucleus accumbens suggest a neural mechanism underlying cue‐evoked goal‐directed behavior
Authors: Yun Irene A. , Nicola Saleem M. , Fields Howard L.
Published: July 2004

Discriminative stimuli (DSs) inform animals that reward can be obtained contingent on the performance of a specific behavior. Such stimuli reinstate drug‐seeking behavior, evoke dopamine release in the nucleus accumbens (NAc) and excite and inhibit specific subpopulations of NAc neurons. Here we show in rats that DSs can reinstate food‐seeking behavior. In addition, we compare the effects of injecting dopamine receptor antagonists into the NAc with those of general NAc inactivation on the performance of a DS task. Selective antagonism of D1 receptors reduced responding to the DS and increased the latency to respond, whereas general inactivation of NAc neuronal activity increased the latency to respond to the DS and increased behaviors extraneous to the task, such as responding in the absence of cues and responding on the inactive lever. Based on these results and our previous findings that NAc neuronal responses to DSs are dependent on the ventral tegmental area, we propose a model for the functional role of NAc neurons in controlling behavioral responses to reward‐predictive stimuli.
Amygdala amino acid and monoamine levels in genetically Fast and Slow kindling rat strains during massed amygdala kindling: a microdialysis study
Authors: Shin Rick S. , Anisman Hymie , Merali Zul , McIntyre Dan C.
Published: July 2004

We investigated the neurochemistry of epileptic seizures in rats selectively bred to be seizure‐prone (Fast) vs. seizure‐resistant (Slow) to amygdala kindling. Microdialysis was used to measure levels of amino acids [glutamate, aspartate and gamma‐aminobutyric acid (GABA)] and monoamines (noradrenaline, dopamine and serotonin) during ‘massed’ stimulation (MS) (every 6 min) of the ipsilateral amygdala for a total of 40 stimulation trials. Behavioral seizure profiles together with their afterdischarge thresholds (ADTs) and associated durations were assessed during the procedure, and subsequently were redetermined 1, 7 and 14 days later. Then normal ‘daily’ kindling commenced and continued until the animal reached the fully kindled state. During MS, several generalized seizures were triggered in Fast rats that were associated with long afterdischarge (AD) durations and intermittent periods of elevated thresholds, but in Slow rats, most stimulations were associated with stable ADTs and short ADs. Progressively increasing extracellular glutamate and decreasing GABA was observed in Fast rats during the MS, whereas Slow rats showed levels similar to baseline values. Levels of noradrenaline and dopamine, but not of serotonin, were also increased in both strains throughout the MS treatment. In Fast rats, a dramatic lengthening of AD durations occurred 7 and 14 days following MS, as well as subsequent strong positive transfer to daily kindling, all of which were not seen in Slow rats. Together, these results show that repeated, closely spaced stimulations of the amygdala can differentially alter excitatory and/or inhibitory transmitter levels in a seizure network, and that sensitivity to this manipulation is genetically determined.
Distinct cellular expressions of creatine synthetic enzyme GAMT and creatine kinases uCK‐Mi and CK‐B suggest a novel neuron–glial relationship for brain energy homeostasis
Authors: Tachikawa Masanori , Fukaya Masahiro , Terasaki Tetsuya , Ohtsuki Sumio , Watanabe Masahiko
Published: July 2004

The creatine/phosphocreatine shuttle system, as catalysed reversibly by creatine kinases, is thought to be essential for the storing and buffering of high phosphate‐bound energy in tissues with high energy demand. In the present study, we aimed to clarify the cellular system of creatine biosynthesis and its energy metabolism in the mouse brain by immunohistochemistry for creatine biosynthetic enzyme S‐adenosylmethionine:guanidinoacetate N‐methyltransferase (GAMT), ubiquitous mitochondrial creatine kinase (uCK‐Mi) and brain‐type cytoplasmic creatine kinase (CK‐B). GAMT was expressed highly in oligodendrocytes and olfactory ensheathing glia and moderately in astrocytes, whereas GAMT was very low in neurons and microglia. By contrast, uCK‐Mi was expressed selectively in neurons and localized in their mitochondria in dendrites, cell bodies, axons and terminals. The distinct and almost complementary distribution of GAMT and uCK‐Mi suggests that the creatine in neuronal mitochondria is derived not only from the circulation, but also from local glial cells associated with these neuronal elements. By contrast, CK‐B was selective to astrocytes among glial populations, and was exclusive to inhibitory neurons among neuronal populations. Interestingly, these cells with high CK‐B immunoreactivity are known to be highly resistant to acute energy loss, such as hypoxia and hypoglycemia. Considering that phosphocreatine generates ATP much faster than the processes of glycolysis and oxidative phosphorylation, the highly regulated cellular expressions of creatine biosynthetic and metabolic enzymes suggest that the creatine/phosphocreatine shuttle system plays a role in brain energy homeostasis through a novel neuron–glial relationship.
Regulation of photoreceptor Per1 and Per2 by light, dopamine and a circadian clock
Authors: Besharse Joseph C. , Zhuang Minhong , Freeman Katie , Fogerty Joseph
Published: July 2004

In the Xenopus laevis retina, a principal model for retinal circadian organization, photoreceptors have all the properties of circadian oscillators. However, rhythmic oscillations of Per1 gene expression in the inner retina (but not photoreceptors) have been reported in mice with the suggestion that mice and frogs have a different retinal circadian organization. Although it is known that two period genes (xPer1 and xPer2) exhibit different temporal patterns of expression in the Xenopus retina, and that one (xPer2) is directly responsive to light and dopamine, it is not known whether this reflects the properties of period genes within photoreceptor oscillators or among distinct retinal cell populations. We addressed this by determining the cellular site of light and dopamine regulated xPer2 expression, and the diurnal expression of both xPer1 and xPer2 using in situ hybridization. Our data show that both xPer1 and xPer2 are expressed in most cell types in the retina, including inner nuclear neurons and ganglion cells. However, light and quinpirole, a dopamine agonist, increase xPer2 levels specifically in photoreceptors, and the effect of quinpirole, but not light, is blocked by pCPT‐cAMP. Furthermore, antiphasic diurnal expression of xPer1 and xPer2 also occurs in photoreceptors. Our analysis does not provide insight into the near constitutive expression of period genes in the inner retina, but supports a model in which light‐ and dopamine regulated‐xPer2 and rhythmic xPer1 play critical roles in entrainment and circadian oscillations within photoreceptors.
TRPV1 and CB1 receptor‐mediated effects of the endovanilloid/endocannabinoid N‐arachidonoyl‐dopamine on primary afferent fibre and spinal cord neuronal responses in the rat
Authors: Sagar Devi R. , Smith Paul A. , Millns Paul J. , Smart Darren , Kendall David A. , Chapman Victoria
Published: July 2004

N‐arachidonoyl‐dopamine (NADA) is an endogenous ligand at TRPV1 and CB1 receptors, which are expressed on primary afferent nociceptors. The aim of this study was to determine contributions of proposed pronociceptive TRPV1 and antinociceptive CB1 receptors to effects of peripheral NADA on primary afferent fibre function. Effects of NADA on primary afferent nociceptor function, determined by whole cell patch clamp and calcium imaging studies of adult dorsal root ganglion (DRG) neurons, were determined. Application of NADA (1 µm) to DRG neurons depolarized the resting membrane potential (Vm) from −58 ± 1 to −44 ± 3 mV (P < 0.00001) and evoked a significant increase (P < 0.0001) in intracellular calcium (74 ± 11% of response to 60 mm KCl), compared to basal. The TRPV1 receptor antagonist capsazepine abolished NADA‐evoked depolarization of Vm (P < 0.0001) and NADA‐evoked calcium responses (P < 0.001), which were also blocked by the CB1 receptor antagonist SR141716A (P < 0.001). Effects of NADA (1.5 µg and 5 µg/50 µL) on mechanically evoked responses of dorsal horn neurons in anaesthetized Sprague–Dawley rats were studied. Intraplantar injection of the higher dose of NADA (5 µg/50 µL) studied significantly inhibited innocuous (8, 10 g) mechanically evoked responses of dorsal horn neurons compared to vehicle, effects blocked by intraplantar injection of SR141716A. Higher weight (26–100 g) noxious‐evoked responses of dorsal horn neurons were also significantly inhibited by NADA (5 µg/50 µL), effects blocked by intraplantar injection of the TRPV1 antagonist, iodo‐resiniferatoxin. NADA has a complex pattern of effects on DRG neurons and primary afferent fibres, which is likely to reflect its dual site of action at TRPV1 and CB1 receptors and the differential expression of these receptors by primary afferent fibres.
Molecular detection and isolation of facultatively methylotrophic bacteria, including Methylobacterium podarium sp. nov., from the human foot microflora
Authors: Anesti Vasiliki , Vohra Jyotsna , Goonetilleka Shalini , McDonald Ian R. , Sträubler Bettina , Stackebrandt Erko , Kelly Donovan P. , Wood Ann P.
Published: July 2004

This is the first study to demonstrate that diverse methylotrophic bacteria occur in the human foot microflora. Polymerase chain reaction (PCR) amplification of DNA from the soles and toe clefts of feet of five subjects indicated Methylobacterium strains to be present in all cases. Polymerase chain reaction amplification also showed the gene for the α‐subunit of methanol dehydrogenase (mxaF) to be present in all samples. Two types of mxaF were recovered, one closest to that of Methylobacterium extorquens and the other most similar to that of Hyphomicrobium methylovorum. Numerous methylotrophic strains able to grow on methylamine were isolated with ease from the feet of nine volunteers. These were found by 16S rRNA analysis to be most closely related to Methylobacterium species, Brevibacterium casei, Pseudomonas strain NZ099 and P. migulae. Three strains from two subjects were of a novel species, Methylobacterium podarium sp. nov. This facultatively methylotrophic, obligately aerobic, pink‐pigmented, non‐motile rod grew with a wide range of multicarbon and one‐carbon compounds including citrate, xylose, mono‐, di‐, and trimethylamine, dimethylsulphide, methanethiol, dimethylsulphoxide, dimethylsulphone and methanol.
Promiscuity in the practice of family therapy
Authors: McNamee Sheila
Published: July 2004

Family therapy has continually confronted choices between polarized positions, each one taken up with zeal because it solved an old dilemma but eventually encountering its own limitations. In this article I suggest that we have evolved to a point where, instead of deciding which is better, we can focus on how to use theories, models and techniques as fluid and flexible resources for action in the therapeutic conversation. Doing so focuses our attention on how we can move in and out of various positions, including those that simplify issues and those that embrace complexity. In addition, our attention is drawn to the ways in which we can make choices between following a model as opposed to engaging in spontaneous dialogue. This promiscuous stance can help trainers and therapists answer questions concerning how we make decisions in therapy. Such promiscuity also positions us to confront our images and expectations of what it means to be a professional.
All aboard in the NHS: collaborating with colleagues who use different approaches
Authors: Speed Bebe
Published: July 2004

Drawing on the author's Mental Health Trust experience, this paper explores and celebrates the diversity of multi‐disciplinary, multi‐model approaches within a National Health Service context and the challenges systemic practitioners encounter in fitting what they have to offer into these complex professional systems. It suggests that we can best meet these challenges both by looking for underlying similarities between approaches and finding ways to accommodate and celebrate the differences.
Psychiatric medication induced obesity: an aetiologic review
Authors: Virk S. , Schwartz T. L. , Jindal S. , Nihalani N. , Jones N.
Published: July 2004

A majority of psychiatric medications are known to generate weight gain and ultimately obesity in some patients. There is much speculation about the prevalence of weight gain and the degree of weight gain during acute and longitudinal treatment, but consensus shows that weight gain is prominent. The present review looked at the aetiology and cause of weight gain associated with psychotropic use and presents hypotheses as to why patients gain weight on antipsychotics, mood stabilizers and antidepressants. It is found that most psychotropic medications induce some weight gain, and clinicians are encouraged to utilize active interventions to alleviate the weight gain in order to prevent more serious obesity related comorbidities.
Childhood sexual abuse and obesity
Authors: Gustafson T. B. , Sarwer D. B.
Published: July 2004

The causes of the current obesity epidemic are multifactorial and include genetic, environmental, and individual factors. One potential risk factor may be the experience of childhood sexual abuse. Childhood sexual abuse is remarkably common and is thought to affect up to one‐third of women and one‐eighth of men. A history of childhood sexual abuse is associated with numerous psychological sequelae including depression, anxiety, substance abuse, somatization, and eating disorders. Relatively few studies have examined the relationship between childhood sexual abuse and adult obesity. These studies suggest at least a modest relationship between the two. Potential explanations for the relationship have focused on the role of disordered eating, particularly binge eating, as well as the possible ‘adaptive function’ of obesity in childhood sexual abuse survivors. Nevertheless, additional research on the relationship between childhood sexual abuse and obesity is clearly needed, not only to address the outstanding empirical issues but also to guide clinical care.
Prevalence of obesity in Spain
Authors: Martínez J. A. , Moreno B. , Martínez‐González M. A.
Published: July 2004

Obesity is a health problem affecting an important proportion of the Spanish population. Overweight is more common among men than women whereas, obesity is more prevalent among women. The most recent data (2001) from self‐reported weight and height measurements of a Spanish representative sample (21120 subjects) revealed that the overall obesity prevalence in Spain was about 13%, while direct anthropometric data obtained from pooled surveys concerning eight Spanish regions (9885 subjects), which were carried out between 1990–2000 the obesity prevalence averaged 14.5%.
Effects of obesity on women's reproduction and complications during pregnancy
Authors: Linné Y.
Published: July 2004

Obesity is increasing rapidly among women all over the world, and more women in fertile ages become overweight and obese. Among all other problems, women who are obese have higher rates of amenorrhoea and infertility. Obese women have a higher risk of complications during pregnancy such as hypertensive diagnoses and gestational diabetes, and delivery complications such as higher rates of caesarean sections and prolonged time of delivery. The aim of this article is to review the consequences of being obese during the reproductive life of a woman.
‘The double identity’ of Taiwanese Chinese: A dilemma of politics and culture rooted in history
Authors: Huang Li‐Li , Liu James H. , Chang Maanling
Published: July 2004

The ‘double identity’ of Taiwanese as both Chinese and Taiwanese identity was measured among both general and student samples using categorical and continuous measures. As predicted, Mingnan (native province) Taiwanese were higher in Taiwanese identity whereas outside‐province Taiwanese were higher in Chinese identity. Both groups shared similar representations of the history of Taiwan, but evaluations of leaders followed patterns of in‐group favoritism. These representations of history were used to predict and find zero correlations between Chinese and Taiwanese identity. Taiwanese and Chinese identities were mutually compatible in cultural domains, and mediated the effect of demographic group. However, in issues concerning politicized allocation decisions (and language), Taiwanese and Chinese identity worked in opposite directions, and demographic group (and a critical evaluation of an historical leader) were significant even after controlling for identity. Implications for social identity theory, realistic group conflict theory, and the cross‐straits relationship are discussed.
Human resilience in a degrading environment: A case study in China
Authors: Van Haaften E. Heleen , Zhenrong Yu , Van de Vijver Fons J. R.
Published: July 2004

Psychological aspects of environmental degradation were studied among 753 Chinese farmers. A good fit was found for a structural equation model postulating a relationship between various input variables (i.e. environmental degradation, socio‐economic status, education, coping, and locus of control), a latent variable (called resilience), and three output variables (i.e. stress, marginalization, and depression). Higher scores on internal locus of control, problem solving, socioeconomic status, and modernity and lower scores on environmental degradation, avoidance, and support seeking were associated with more resilience.
Self‐construal as a predictor of communal and exchange orientation in Taiwan and the USA
Authors: Bresnahan Mary Jiang , Chiu Hiu Chih , Levine Timothy R.
Published: July 2004

Based on a three‐dimensional model of self‐construal (independent, collective interdependent, and relational interdependent self‐construal), the present study investigated whether self‐construal systematically related to exchange and communal orientation with data (357 participants) collected in Taiwan (N = 178) and the USA (N = 179). United States participants scored significantly higher on all scales except for relational interdependent self‐construal. Females exhibited significantly higher scores for relational interdependent self‐construal and communal orientation. As predicted, independent self‐construal was related to exchange orientation and relational interdependent self‐construal was related to communal orientation. However, in contrast to what was expected, collective interdependent self‐construal was only marginally related to communal orientation. The findings for scales revised for validity were compared with scales including all items. This comparison disclosed differences for exchange orientation.