bluuebunny/crossref_metadata_2025 huggingface dataset:
TGF‐β effects on airway smooth muscle cell proliferation, VEGF release and signal transduction pathways
Authors: SHIN Joo Hwa , SHIM Jae Won , KIM Deok Soo , SHIM Jung Yeon
Published: January 2009

Background and objective:  Airway smooth muscle (ASM) cell hyperplasia is a key feature of airway remodelling. Mitogen‐activated protein kinase (MAPK) and phosphoinositide 3‐kinase (PI3K) are key components in signal transduction associated with cell proliferation; MAPK consists of the extracellular signal‐regulated kinase (ERK), p38MAPK and c‐Jun NH2‐terminal kinase (JNK). The effect of transforming growth factor (TGF)‐β on the proliferation of ASM cells, the release of vascular endothelial growth factor (VEGF) by ASM cells and relevant signal transduction pathways were investigated.

Methods:  ASM cells were growth‐arrested for 48 h then stimulated with platelet‐derived growth factor (PDGF), TGF‐β and dexamethasone. ASM cells were also treated with specific inhibitors of MAPK (PD98059), PI3K (wortmannin) and JNK (SP600125). Cell proliferation and VEGF concentrations were measured.

Results:  TGF‐β neither augmented ASM cell proliferation nor showed a synergistic effect on PDGF‐mediated ASM cell proliferation. Dexamethasone did not suppress ASM cell proliferation. VEGF release was augmented by TGF‐β stimulation in a time‐dependent manner, and was further enhanced by co‐stimulation with PDGF and TGF‐β. Dexamethasone suppressed VEGF release significantly. TGF‐β enhanced PI3K phosphorylation, while PDGF augmented both ERK and PI3K phosphorylation. Wortmannin inhibited both TGF‐β‐ and PDGF‐stimulated VEGF release.

Conclusions:  TGF‐β may facilitate airway remodelling by promoting VEGF release through the PI3K pathway, rather than via ASM cell proliferation.
In vitro cytotoxicity of CD8+ T cells in multi‐drug‐resistant tuberculosis. A preliminary report
Authors: SADA‐OVALLE Isabel , TORRE‐BOUSCOULET Luis , VALDEZ‐VÁZQUEZ Rafael , LASCURAIN Ricardo
Published: January 2009

Background and objective:  Specific CD8+ T‐cell cytotoxicity has been recognized as being involved in the elimination of drug‐susceptible tuberculosis (DS‐TB). Given that there is currently no information on the cytotoxic effector functions of CD8+ T cells in multi‐drug‐resistant tuberculosis (MDR‐TB), our objective was to analyse the cytotoxic activity, both basal and stimulated, of CD8+ T cells from MDR‐TB patients and compare it with that of DS‐TB patients, as well as purified protein derivative (PPD)+ and PPD− subjects.

Methods:  Cytotoxic activity of CD8+ T cells from MDR‐TB patients, DS‐TB patients, PPD+ and PPD− subjects was measured by a colorimetric assay, using H37Rv culture filtrate protein as the antigenic stimulus.

Results:  Twenty‐eight subjects were studied (7 MDR‐TB patients, 7 DS‐TB patients, 7 PPD+ subjects and 7 PPD− subjects). In the presence of the antigenic stimulus, the cytotoxic activity of CD8+ T cells from MDR‐TB patients (% lysis) increased from 6.7% to 59.6% (P < 0.001). In DS‐TB patients lysis increased from 3.2% to 22.5% (P < 0.001), whereas in PPD+ subjects it increased from 2.7% to 12.0% (P < 0.001) and in PPD− subjects from 1.3% to 3.2% (P < 0.001). Basal cytotoxic activity was significantly higher for MDR‐TB patients than PPD+ and PPD− subjects (P = 0.003), but not compared with that for DS‐TB patients (P = 0.05). Stimulated cytotoxic activity was highest for MDR‐TB patients.

Conclusions:  CD8+ T cells from MDR‐TB patients showed an exaggerated cytotoxic activity after antigenic stimulation. Further studies are required to elucidate the role of this response in the immunopathogenesis of MDR‐TB.
En bloc paediatric kidney transplant: is this the best use of a scarce resource?
Authors: Lam Vincent W. T. , Laurence Jerome M. , Robertson Paul , Hawthorne Wayne , Ryan Brendan J. , Lau Howard M. H. , Allen Richard D. M. , Pleass Henry C. C.
Published: January 2009

Background:  Kidney transplants using organs from paediatric cadaver donors are uncommon and technically difficult. It has become accepted practice to transplant both kidneys en bloc from donors of 5 years into a single recipient. We aim to compare outcomes of en bloc kidney (EBK) transplants versus single kidney (SK) transplants from cadaver donors of age 5 years and lesser.

Methods:  Data reported to Australia and New Zealand Dialysis and Transplant Registry from 1989 to 2004 were analysed.

Results:  From donors 5 years of age and younger, there were 33 EBK and 38 SK transplants carried out. Overall graft survival rates at 1 and 5 years were 78 and 61%, respectively, in the EBK group and 63 and 55%, respectively, in the SK group (P = 0.94). Vascular thrombosis was the most common cause of early graft loss with an incidence of 11 and 18%, respectively, in the EBK and SK groups (P = 0.5).

Conclusion:  There is a trend towards a lower vascular thrombosis rate and a better long‐term graft survival in EBK transplants. These transplants will remain a technical challenge for the surgeon and EBK transplants should remain the technique of choice for donors of 5 years and lesser.
Aortic fat pad and atrial fibrillation: cardiac lymphatics revisited
Authors: Lupinski Ryszard W.
Published: January 2009

The lymphatics of the heart have not generated any broad or sustained interest among clinicians. Few publications on cardiac lymphatics are available, the anatomy is not routinely known and the true role of cardiac lymphatics remains doubtful. One important anatomical concept needing clarification is that of the lymphatic drainage of conduction tissue. The sinoatrial node lymphatic collector and right principal lymphatic trunk are both incorporated into the aortic fat pad of the ascending aorta and are the most frequently damaged lymphatic vessels during cardiac surgery. Thus, preservation of the aortic fat pad and its lymphatic collectors should reduce the incidence of new atrial fibrillation observed in patients after cardiac surgery. This review assesses current knowledge of cardiac lymphatics and shows their possible role in triggering arrhythmias in the postoperative period.
Regional cortical blood flow changes following sodium lactate infusion in Alzheimer's disease
Authors: Kálmán János , Palotás András , Kis Gabriella , Boda Krisztina , Túri Piroska , Bari Ferenc , Domoki Ferenc , Dóda Ildikó , Árgyelán Miklós , Vincze Gábor , Séra Teréz , Csernay László , Janka Zoltán , Pávics László
Published: January 2009

Bilateral temporoparietal hypoperfusion is a characteristic single photon emission computed tomography (SPECT) finding in Alzheimer's disease (AD). Lactate is a metabolic vasodilator and is known to provoke increased cerebral blood flow (CBF) in healthy adults. This work investigated whether lactate, which is present in high concentrations in AD cerebrospinal fluid, affects AD‐specific perfusion abnormalities. Twenty mild‐to‐moderately demented AD probands participated in the self‐controlled study. The regional CBF was examined utilizing 99mTc‐HMPAO SPECT after sodium lactate infusion (0.5 m, 5 mL/kg body weight) and 0.9% NaCl infusion, one on each of two separate days. Despite the vasodilatator effects of sodium lactate, AD rCBF patterns did not show increase in temporo‐parietal regions after its infusion. AD‐specific bi‐temporo‐parietal reduction in CBF was accompanied by further hypoperfusion in the parieto‐occipital areas after the sodium lactate infusion in seven patients, while no CBF changes were observed in the case of the remaining 13 probands. The pattern of the CBF abnormalities was not correlated with the apolipoprotein E genotype. The decreased vascular responsiveness to sodium lactate reflects disturbed vasoregulatory processes in AD and it is unlikely that lactate would have any relevance in the treatment of AD‐related cerebral hypoperfusion, but could be used to improve the value of perfusion SPECT in the diagnosis of AD.
Retinoic acid synthesis by a population of NG2‐positive cells in the injured spinal cord
Authors: Mey Jörg , J. Morassutti Dante , Brook Gary , Liu Rong‐Huan , Zhang Yi‐Ping , Koopmans Guido , McCaffery Peter
Published: January 2009

Retinoic acid (RA) promotes growth and differentiation in many developing tissues but less is known about its influence on CNS regeneration. We investigated the possible involvement of RA in rat spinal cord injury (SCI) using the New York University (NYU) impactor to induce mild or moderate spinal cord contusion injury. Changes in RA at the lesion site were determined by measuring the activity of the enzymes for its synthesis, the retinaldehyde dehydrogenases (RALDHs). A marked increase in enzyme activity occurred by day 4 and peaked at days 8–14 following the injuries. RALDH2 was the only detectable RALDH present in the control or injured spinal cord. The cellular localization of RALDH2 was identified by immunostaining. In the noninjured spinal cord, RALDH2 was detected in oligodendroglia positive for the markers RIP and CNPase. Expression was also intense in the arachnoid membrane surrounding the spinal cord. After SCI the increase in RALDH2 was independent of the RIP‐ and CNPase‐positive cells, which were severely depleted. Instead, RALDH2 was present in a cell type not previously identified as capable of synthesizing RA, that expressed NG2 and that was negative for markers of astrocytes, oligodendroglia, microglia, neurons, Schwann cells and immature lymphocytes. We postulate that the RALDH2‐ and NG2‐positive cells migrate into the injured sites from the adjacent arachnoid membrane, where the RALDH2‐positive cells proliferate substantially following SCI. These findings indicate that close correlations exist between RA synthesis and SCI and that RA may play a role in the secondary events that follow acute SCI.
Estrogen enhances light‐induced activation of dorsal raphe serotonergic neurons
Authors: Abizaid Alfonso , Mezei Gabor , Thanarajasingam Gita , Horvath Tamas L.
Published: January 2009

The serotonergic system has been implicated in the modulation of physiological processes including circadian rhythms, learning, memory, mood and food intake. In females, cessation of ovarian function produces deleterious changes in all of these processes and estrogen treatment often ameliorates these conditions. Estrogen may produce these effects by acting on the midbrain raphe, an estrogen‐sensitive region that receives direct projections from sensory systems. Here we examined the ability of estradiol to modulate neuronal responses of neurons within raphe nuclei to photic stimulation. Ovariectomized rats treated with estradiol or cholesterol were killed 1 h after the normal onset of light (Zeitgeber time 0) or after a 2‐h phase advance (Zeitgeber time 22). In a second study, estradiol‐treated ovariectomized rats under constant dark conditions were exposed to light 2 h before the subjective onset of circadian time [(CT)22] and killed 1 h later (CT23). The brains from all animals were processed for Fos and/or serotonin (5‐HT) immunocytochemistry. Comparisons showed that the phase shift increased Fos immunoreactivity in all dorsal raphe nucleus (DRN) regions. Although estradiol did not alter the overall number of Fos‐positive nuclei, it significantly increased the number of Fos/5‐HT double‐labelled cells in the medial and lateral DRN. In contrast, neither a phase shift nor estradiol altered the number of Fos‐immunoreactive cells or the proportion of Fos‐positive 5‐HT cells in the median raphe nucleus. Results reveal that the DRN 5‐HT system responds to changes in the light : dark cycle and that these responses are modulated by estrogen.
Ratio and time requirements on operant schedules: effort‐related effects of nucleus accumbens dopamine depletions
Authors: Mingote Susana , Weber Suzanne M. , Ishiwari Keita , Correa Mercè , Salamone John D.
Published: January 2009

Accumbens dopamine (DA) depletions produce deficits that are related to the ratio requirement of the operant schedule; however, it is also possible that time without reinforcement is a factor. The present study examined the effects of accumbens DA depletions in rats using variable interval (VI) schedules with additional fixed ratio (FR) requirements. Four VI schedules were used (VI 60/FR 1, VI 120/FR 1, VI 60/FR 10, VI 120/FR 10). Attachment of the additional work requirement increased response rates under control conditions. After surgery, there was no interaction between interval level (i.e. 60 vs. 120 s) and DA depletion, but there was a significant interaction between ratio requirement (i.e. 1 vs. 10) and DA depletion within the first week after surgery. DA depletions substantially impaired performance on the schedules with added FR 10 requirements, an effect that was largely dependent upon a reduction in fast responses (i.e. interresponse times less than 1.0 s). There was little effect of DA depletion on overall responding on VI 60/FR 1 and VI 120/FR 1 schedules. DA depletions also increased the tendency to take long pauses in responding (i.e. > 20.0 s), and this effect was evident across all schedules tested. Thus, accumbens DA depletions interact with work requirements and blunt the rate‐enhancing effects of moderate size ratios, and also enhance the tendency to pause. Attachment of ratio requirements to interval schedules is a work‐related response cost that provides a challenge to the organism, and DA in nucleus accumbens appears to be necessary for adapting to this challenge.
IGF‐I neuroprotection in the immature brain after hypoxia‐ischemia, involvement of Akt and GSK3β?
Authors: Brywe Katarina G. , Mallard Carina , Gustavsson Malin , Hedtjärn Maj , Leverin Anna‐Lena , Wang Xiaoyang , Blomgren Klas , Isgaard Jörgen , Hagberg Henrik
Published: January 2009

Insulin‐like growth factor I (IGF‐I) is a neurotrophic factor that promotes neuronal growth, differentiation and survival. Neuroprotective effects of IGF‐I have previously been shown in adult and juvenile rat models of brain injury. We wanted to investigate the neuroprotective effect of IGF‐I after hypoxia‐ischemia (HI) in 7‐day‐old neonatal rats and the mechanisms of IGF‐I actions in vivo. We also wanted to study effects of HI and/or IGF‐I on the serine/threonine kinases Akt and glycogen synthase kinase 3β (GSK3β) in the phophatidylinositol‐3 kinase (PI3K) pathway. Immediately after HI, phosphorylated Akt (pAkt) and phosphorylated GSK3β (pGSK3β) immunoreactivity was lost in the ipsilateral and reduced in the contralateral hemisphere. After 45 min, pAkt levels were restored to control values, whereas pGSK3β remained low 4 h after HI. Administration of IGF‐I (50 µg i.c.v.) after HI resulted in a 40% reduction in brain damage (loss of microtubule‐associated protein) compared with vehicle‐treated animals. IGF‐I treatment without HI was shown to increase pAkt whereas pGSK3β decreased in the cytosol, but increased in the nuclear fraction. IGF‐I treatment after HI increased pAkt in the cytosol and pGSK3β in both the cytosol and the nuclear fraction in the ipsilateral hemisphere compared with vehicle‐treated rats, concomitant with a reduced caspase‐3‐ and caspase‐9‐like activity. In conclusion, IGF‐I induces activation of Akt during recovery after HI which, in combination with inactivation of GSK3β, may explain the attenuated activation of caspases and reduction of injury in the immature brain.
Presynaptic ‘Cav2.3‐containing’ E‐type Ca2+ channels share dual roles during neurotransmitter release
Authors: Kamp M. A. , Krieger A. , Henry M. , Hescheler J. , Weiergräber M. , Schneider T.
Published: January 2009

Ca2+ influx into excitable cells is a prerequisite for neurotransmitter release and regulated exocytosis. Within the group of ten cloned voltage‐gated Ca2+ channels, the Cav2.3‐containing E‐type Ca2+ channels are involved in various physiological processes, such as neurotransmitter release and exocytosis together with other voltage‐gated Ca2+ channels of the Cav1, Cav2 and Cav3 subfamily. However, E‐type Ca2+ channels also exhibit several subunit‐specific features, most of which still remain poorly understood. Cav2.3‐containing R‐type channels (here called ‘E‐type channels’) are also located in presynaptic terminals and interact with some synaptic vesicle proteins, the so‐called SNARE proteins, although lacking the classical synprint interaction site. E‐type channels trigger exocytosis and are also involved in long‐term potentiation. Recently, it was shown that the interaction of Cav2.3 with the EF‐hand motif containing protein EFHC1 is involved in the aetiology and pathogenesis of juvenile myoclonic epilepsy.
Akt is altered in an animal model of Huntington's disease and in patients
Authors: Colin Emilie , Régulier Etienne , Perrin Valérie , Dürr Alexandra , Brice Alexis , Aebischer Patrick , Déglon Nicole , Humbert Sandrine , Saudou Frédéric
Published: January 2009

The insulin‐like growth factor I (IGF‐1)/Akt pathway plays a crucial role in Huntington's disease by phosphorylating the causative protein, polyQ‐huntingtin, and abolishing its toxic properties [Humbert et al. (2002)Dev. Cell, 2, 831–837; Rangone et al. (2004)Eur. J. Neurosci., 19, 273–279]. Therefore, dysregulation of this pathway may be essential for disease progression. In the present report, we thus aimed to analyse the status of Akt in brain or in peripheral tissues in Huntington's disease. Using a genetic model of Huntington's disease in rat that reproduces neuronal dysfunction and death, we show a progressive alteration of Akt during neuronal dysfunction and prior neurodegeneration. By analysing a limited number of lymphoblasts and lymphocytes, we detected modifications of Akt in Huntington's disease patients confirming a dysregulation of Akt in the disease process. Finally, we demonstrate that during late stages of the disease, Akt is cleaved into an inactive form by caspase‐3. These observations demonstrate a progressive but marked alteration of this pro‐survival pathway in Huntington's disease, and further implicate it as a key transduction pathway regulating the toxicity of huntingtin.
Zebrafish embryos are susceptible to the dopaminergic neurotoxin MPTP
Authors: Lam Chen Sok , Korzh Vladimir , Strahle Uwe
Published: January 2009

The neurotoxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) induces selective loss of dopaminergic neurons in the mammalian midbrain, eliciting symptoms characteristic of Parkinson's disease. By exploiting the advantages of zebrafish embryos, we report here that dopaminergic neurons in this species are specifically perturbed when exposed to MPTP. In contrast to mammals, the zebrafish does not possess a midbrain dopaminergic system. Instead, the main population of neurons expressing the dopamine transporter is located in the posterior tuberculum of the diencephalon. Exposure of embryos to MPTP led to a pronounced reduction in the number of dopaminergic cells in the diencephalon. This effect can be reversed by deprenyl, a specific inhibitor of monoamine oxidase B that catalyses the conversion of MPTP to its active metabolite, MPP+. Similarly, direct treatment of embryos with MPP+ abolished the diencephalic dopaminergic neurons. These larvae also demonstrated behavioural defects in swimming responses. Thus, dopaminergic neurons in the posterior tuberculum of the zebrafish may be homologous to the midbrain dopaminergic system of mammals. In addition, the mechanism behind the loss of dopaminergic neurons following pharmacological perturbation may be conserved among vertebrates and suggest that the zebrafish can be used as a convenient and economical system to study the pathogenesis of Parkinson's disease and for testing potential therapeutic strategies.
Antagonist‐induced supersensitivity of mGlu1 receptor signalling in cerebellar granule cells
Authors: Lavreysen Hilde , Willemoens Tineke , Leysen Joseé E. , Lesage Anne S. J.
Published: January 2009

We investigated the effect of 24 h sustained treatment with the mGlu1 receptor antagonist CPCCOEt on mGlu1 receptor signalling in primary cultures of rat cerebellar granule cells. In the absence of ionotropic glutamate (iGlu) blockers, the maximal inositol phosphate (IP) response (Emax) but not the potency of glutamate was significantly increased when cells were pre‐exposed for 24 h with CPCCOEt. When the contribution of iGlu receptors to the glutamate‐induced IP response was eliminated with the use of DNQX, the Emaxwas again increased but also the concentration eliciting 50% of the maximal glutamate stimulus was significantly decreased. In the absence of iGlu receptor inhibitors, the Emaxof quisqualate, which likely mediates IP accumulation only via the mGlu1 receptor, was significantly increased in CPCCOEt‐pretreated cells. Also, less quisqualate was needed to reach the same IP effect. The potency of R193845, a selective mGlu1 receptor antagonist, was significantly decreased in antagonist‐pretreated cells. These findings demonstrate that 24 h sustained antagonist treatment can render mGlu1 receptors in neurons supersensitive to agonists, with a concomitant decrease in the effectiveness of antagonists.
Postnatal ontogeny of hippocampal expression of the mineralocorticoid and glucocorticoid receptors in the common marmoset monkey
Authors: Pryce Christopher R. , Feldon Joram , Fuchs Eberhard , Knuesel Irene , Oertle Thomas , Sengstag Christian , Spengler Marianne , Weber Elizabeth , Weston Anna , Jongen‐Rélo Ana
Published: January 2009

The mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) are nuclear transcription factors that mediate many of the basal and stress functions and effects of the corticosteroid hormones, including those related to brain development. Despite this, relatively little is known about the postnatal ontogeny of MR and GR gene and protein expression in the central nervous system, and this is particularly true of the primates, including humans. Here we describe the postnatal ontogeny of central MR and GR gene and protein expression in the common marmoset monkey. By developing marmoset‐specific riboprobes and usingin situhybridization, it was demonstrated that MR mRNA expression in the dentate gyrus and Ammon's horn was significantly greater in marmoset infants (aged 4–6 weeks) than in neonates (1–2 days), juveniles (4–5 months) and adults (3–6 years), with expression in the latter three ontogenetic stages being broadly similar. In the same subjects and ontogenetic stages, GR mRNA expression was developmentally consistent in the marmoset dentate gyrus and Ammon's horn, as well as in the paraventricular nucleus of the hypothalamus. Qualitative immunohistochemical comparison of infants and adults demonstrated that MR protein expression in the hippocampus was, as for mRNA, also greater in infants than adults, and that hippocampal GR protein was, as for mRNA, also similar in infants and adults. The increase in MR mRNA expression between the stages of neonate and infant co‐occurred with a reduction in basal plasma ACTH and cortisol titres. The ontogenetic profiles of MR and GR gene expression in the marmoset monkey are therefore fundamentally different from those described for the rat and the mouse. This evidence for the postnatal ontogeny of central corticosteroid nuclear receptor expression in a primate is important for understanding both the developmental stage‐specific significance of stress exposure and its potential long‐term effects on health and disease.
Voluntary exercise rescues deficits in spatial memory and long‐term potentiation in prenatal ethanol‐exposed male rats
Authors: Christie Brian R. , Swann Sarah E. , Fox Christopher J. , Froc David , Lieblich Stephanie E. , Redila Van , Webber Alina
Published: January 2009

Prenatal ethanol exposure can lead to long‐lasting impairments in the ability to process spatial information in rats, as well as produce long‐lasting deficits in the ability of animals to exhibit long‐term potentiation, a biological model of learning and memory processing. Conversely, we have recently shown that both spatial memory and long‐term potentiation can be enhanced in animals that are given access to a running wheel in their home cage. In the present study, Sprague–Dawley rat dams were given one of three diets throughout gestation: (i) a liquid diet containing ethanol (35.5% ethanol‐derived calories); (ii) a liquid diet, isocaloric to the ethanol diet, but with maltose‐dextrin substituting for the ethanol derived calories and (iii) an ad libitum diet of standard rat chow. At weaning (28 days) animals were housed individually in either a standard rat cage, or a cage that contained a running wheel. Adult offspring were tested on a two trial version of the Morris water maze beginning at postnatal day 60, for five consecutive days. Following this, the capacity of the perforant path to dentate gyrus pathway to sustain long‐term potentiation was examined in these animals using theta‐patterned conditioning stimuli. Our results demonstrate that prenatal ethanol exposure can produce pronounced deficits in both spatial memory and long‐term potentiation, but that allowing animal's access to voluntary exercise can attenuate these deficits to the point that those exposed to ethanol prenatally can no longer be differentiated from control animals. These findings indicate that voluntary exercise may have therapeutic benefits for individuals that have undergone prenatal ethanol exposure.
Increased osteopontin expression following intranigral lipopolysaccharide injection in the rat
Authors: Iczkiewicz Joanna , Rose Sarah , Jenner Peter
Published: January 2009

Nigral cell death in Parkinson's disease is characterized by glial cell activation leading to inflammatory changes. Osteopontin (OPN) is a glycosylated phosphoprotein that is induced by inflammatory mediators and which we have previously shown to be present in the substantia nigra. However, the role of OPN in the nigral inflammation is not known. We now report on the effects of lipopolysaccharide (LPS)‐induced glial cell activation in the substantia nigra of rats on OPN expression. LPS administration induced dopaminergic cell death as shown by reduced nigral tyrosine hydroxylase immunoreactivity. There was a corresponding time‐dependent increase in both OPN mRNA, which was maximal at 48 h, and protein levels, which peaked at 72 h before returning to control levels by 120 h. This increase was accompanied by marked reactive gliosis as shown by increased OX‐42, glial fibrillary acidic protein (GFAP) and ED1 immunoreactivity. OX‐42‐positive cells increased in a time‐dependent manner, peaking at 72 h before returning to control levels at 120 h. Similarly, ED1‐positive cells were present in their greatest numbers at 24 h but then gradually declined. These changes mirrored the alterations occurring in OPN protein and OPN mRNA, respectively. In contrast, GFAP‐positive cells only started to increase in number at 120 h. Colocalization studies showed that OPN was present in both ED1‐ and OX‐42‐positive cells but not in GFAP‐positive cells. These data confirm that intranigral injection of LPS induces a rapid and marked gliosis that accompanies the loss of tyrosine hydroxylase‐positive neurones and suggest that, after glial cell activation, enhanced expression of OPN occurs linked to increased numbers of microglia and/or macrophages. This suggests that OPN may be functionally important in the control of inflammatory changes.
Selective effects of partial striatal 6‐OHDA lesions on information processing in the rat
Authors: Courtière Alain , Hardouin Jeannine , Locatelli Virginie , Turle‐Lorenzo Nathalie , Amalric Marianne , Vidal Franck , Hasbroucq Thierry
Published: January 2009

The present study was aimed at characterizing the cognitive deficits caused by the degeneration of nigrostriatal dopamine (DA) pathways by using the additive factor logic [Sternberg, S. (1969) Acta Psychol., 30, 276–315], a powerful reaction time (RT) method developed in humans and recently introduced in the rat [Courtière, A., Hardouin, J., Hasbroucq, T., Possamaï, C.‐A. & Vidal, F. (2000) Behav. Process., 50, 113–121]. Long‐Evans rats were trained to respond to left or right (lateral) visual cues in a choice RT task. Two task factors, signal intensity and force requirement, were manipulated. Partial bilateral 6‐OHDA lesions of DA nerve terminals in the striatum were then performed and their effects tested for up to 7 weeks following surgery. Reaction time was lengthened from the 2nd to the 4th week postlesion. This alteration was independent of force requirement, thereby suggesting that the related motor processes were not influenced by the DA depletion. During the 2nd week postlesion, the RT increase was accompanied by a disappearance of the effect of signal intensity, showing that the lesion altered stimulus‐related processes. From the 3rd week the signal intensity effect was re‐established although RT was still increased, indicating that the stimulus‐related processes had recovered while other central processes were still impaired. From the 5th week after surgery, the lesioned animals had completely recovered from the RT deficits induced by the lesion. These results point at the involvement of striatal DA in sensory and central information processes.
Development of pontine noradrenergic A5 neurons requires brain‐derived neurotrophic factor
Authors: Guo Hong , Hellard David T. , Huang Lennox , Katz David M.
Published: January 2009

Pontine noradrenergic A5 neurons play a pivotal role in maturation and regulation of the brainstem respiratory rhythm‐generating network. Analysis of newborn brain‐derived neurotrophic factor (BDNF)‐null mice revealed a marked loss of tyrosine hydroxylase‐positive A5 neurons compared to wildtype controls that was rescued by null mutation of the proapoptotic gene Bax. In cultures of the A5 region from E12.5 rat embryos, BDNF significantly increased the number and branching of tyrosine hydroxylase‐positive neurons. Immunoneutralization of endogenous glial cell line‐derived neurotrophic factor partially inhibited the BDNF‐dependent increase in the number of tyrosine hydroxylase‐positive cells without affecting neurite number. The A5 nucleus is the first brainstem cell group identified at which BDNF is required in vivo for development of neurons critical for cardiorespiratory control.
Multiple defects in the formation of rat cortical axonal pathways following prenatal X‐ray irradiation
Authors: Li Hong‐Peng , Honma Shizuka , Miki Takanori , Takeuchi Yoshiki , Takeuchi Kosei , Kawano Hitoshi
Published: January 2009

Prenatal X‐ray irradiation is known to result in severe defects of neuronal migration and laminar formation in the cerebral cortex. We examined the formation of cortical afferent and efferent pathways in rats that had been exposed to X‐ray irradiation (1.0 Gy) at embryonic day 14 (E14), by birthdating with bromodeoxyuridine (BrdU) and axonal labeling with 1‐1′‐dioctodecyl‐3,3,3′,3′‐ tetramethyl‐indocarbocyanine perchlorate (DiI), in addition to immunohistochemical staining for various axonal markers including neurofilament, and cell adhesion molecules L1 and TAG‐1. The results obtained were as follows. (i) The neuroepithelium formed germinal rosettes and concavities in the cortical anlage from 2 days after irradiation. Neurons generated in the neuroepithelium accumulated to form subcortical heterotopia and obstructed pathway formation in the intermediate zone, resulting in an aberrant trajectory of TAG‐1‐immunoreactive cortical efferent axons. (ii) In rats exposed to X‐ray irradiation at E14, cystic cavities were formed in the cortex–striatum boundary region between E15 and E17, probably because of delayed cell death of neurons generated at E14. These cavities transiently interrupted both cortical afferent (L1‐positive) and efferent (TAG‐1‐positive) axons. (iii) X‐ray irradiation at E14 partially destroyed subplate neurons (transient targets of thalamic afferent axons) and disturbed the arrangement of the subplate layer. This resulted in a misrouting of neurofilament‐ and L1‐immunoreactive thalamocortical axons that obliquely traversed the cortical plate to run up to the superficial layer. The present study demonstrates for the first time that X‐ray irradiation during initial cortical development causes multiple defects in the formation of cortical afferent and efferent pathways.
Right‐hemisphere motor facilitation by self‐descriptive personality‐trait words
Authors: Molnar‐Szakacs Istvan , Uddin Lucina Q. , Iacoboni Marco
Published: January 2009

The emergent picture from the literature on the processing of self‐related information suggests that in addition to the neural mechanisms involved in recognizing one's own face, there may also be neural representations of the self that are modality independent and favour the right hemisphere. We used focal, single‐pulse transcranial magnetic stimulation in human subjects to assess cortical excitability during covert reading of self‐descriptive personality‐trait words. We hypothesized that the right hemisphere would show a greater overall facilitation to personality‐trait words than the left hemisphere. Overall, personality‐trait words led to significantly greater motor facilitation in the right hemisphere than in the left hemisphere. In addition, words rated as ‘never’ self‐characteristic yielded significant right hemisphere facilitation, and words rated as ‘always’ self‐characteristic showed a similar trend. The results are discussed in terms of the notion that the right hemisphere plays a dominant role in both self‐relevant processing and the processing of affective stimuli.
A pentylenetetrazole‐induced generalized seizure in early life enhances the efficacy of muscarinic receptor coupling to G‐protein in hippocampus and neocortex of adult rat
Authors: Potier Soizic , Sénécal Jacques , Chabot Jean‐Guy , Psarropoulou Caterina , Descarries Laurent
Published: January 2009

We have previously shown that exposure to the anti‐cholinesterase eserine provokes interictal‐like discharges in the CA3 area of hippocampal slices from adult rats in which a generalized seizure has been induced by pentylenetetrazole (PTZ) when immature (at 20 days). Such increased responsiveness to acetylcholine (ACh) was not associated with any change in hippocampal acetylcholine or γ‐aminobutyric acid (GABA) content, GABAergic inhibition or density of ACh innervation, but was blocked by the muscarinic receptor antagonist atropine. We therefore turned to quantitative radioligand binding autoradiography,in situhybridization and the [35S]GTPγS method to assess the properties of hippocampal and neocortical muscarinic receptors in adult rats having experienced a PTZ seizure at P20. The densities of M1 and M2 receptor binding sites, respectively labeled with [3H]pirenzepine and [3H]AFDX‐384, as well as the amount of m1, m2 and m3 receptor mRNAs, did not differ from control in the hippocampus and neocortex of these rats. In contrast, in PTZ rats, both brain regions displayed a marked increase in [35S]GTPγS incorporation stimulated by ACh, bethanechol and particularly oxotremorine. This finding indicates that a generalized seizure in immature rat can entail a long‐term and presumably permanent increase in the efficacy of G‐protein coupling to muscarinic receptors in the hippocampus and neocortex of the adult. By analogy, such a mechanism could account for the susceptibility to epilepsy of human adults having suffered from prolonged convulsions in early life.
Target‐controlled inhalation induction with sevoflurane in children: a prospective pilot study
Authors: FRITSCH NICOLAS , NOUETTE‐GAULAIN KARINE , BORDES MARYLINE , SEMJEN FRANCOIS , MEYMAT YVES , CROS ANNE‐MARIE
Published: January 2009

Background:  Target‐controlled inhalation induction (TCII) with sevoflurane is becoming possible with new anesthesia platforms. Although TCII has already been performed in adults, it remains to be evaluated in children.

Methods:  In a prospective study, we compared TCII using the Felix AInOC™ anesthetic station (Taema, Anthony, France) to our standard protocol inhalation induction in children scheduled for elective surgery under general anesthesia. After preoxygenation, sevoflurane induction was performed in both groups without priming of the circuit. Sufentanil was administered after venous line placement.

Results:  In the TCII group, no overdosage or underdosage was observed except in two children where TCII failed owing to high agitation, and the number of adjustments was lower compared with our standard protocol inhalation induction (1(1–2.5[0–5]) vs 6(5–6[4–10]) respectively). Moreover, the delay to obtain target end‐tidal sevoflurane concentration was shorter in the TCII group (2(1.6–2.7[1.3–4]) min vs 3.4(2.5–3.8[2.3–6.5]) min respectively). No significant difference in the delay of loss of consciousness or in the conditions for intubation or laryngeal mask placement was observed between the groups.

Conclusion:  The Felix AInOC™ allows TCII to be performed satisfactorily in children. Manual inhalation induction induced a higher number of adjustments and overdosages.
Noncolonic cancer stem cells in bone marrow of colorectal cancer patients
Authors: Altomare D. F. , Guanti G. , Hoch J. , Vician M. , Krivokapic Z. , Bergamaschi R. ,   for the Colorectal Micrometastases Study Group (see )
Published: January 2009

Objective  To investigate whether preoperative noncolonic cancer stem cells in bone marrow (BM) of R0 colorectal cancer (CRC) patients are cancer cells and impact on liver metastases (LM) rates.

Method  Prospective data on continuous CRC patients were collected from five centres. Bone marrow aspirates, taken at laparotomy, were sent to a single lab. Noncolonic cancer stem cells were defined according to UICC. A quantity of 3 × 106 BM cells per patient was processed with monoclonal antibodies against cytokeratin 20. APC or p53 gene mutation and microsatellite instability (MSI) were assessed in primary tumours (PT) by single‐strand conformation polymorphism. Noncolonic cancer stem cells in BM of PT mutation or MSI‐positive patients were isolated with immunobeads coated with magnetically labelled anti‐human epithelial antigen antibody and DNA‐screened for mutations.

Results  Although 199 patients were enrolled, 162 patients were available for analysis. No patients were lost to follow‐up. Twenty‐five (2–170) noncolonic cancer stem cells were found in BM of 40 patients. Twenty‐two patients developed LM at 36‐month follow‐up. Adenomatous polyposis coli (APC) or p53 gene mutation or MSI were identified in the PT of 78 patients. The same gene mutations or MSI were not found in noncolonic cancer stem cells of the BM of these patients. After adjustment, there was no significant effect of confounding factors. Noncolonic cancer stem cells in BM had no impact on LM rates, cancer‐specific death rates, or all death rates.

Conclusions  Preoperative noncolonic cancer stem cells in BM of R0 CRC patients were not cancer cells and had no impact on LM rates.
Colonic diverticulitis: a prospective analysis of diagnostic accuracy and clinical decision‐making
Authors: Toorenvliet B. R. , Bakker R. F. R. , Breslau P. J. , Merkus J. W. S. , Hamming J. F.
Published: January 2009

Objective  To evaluate the diagnostic accuracy of clinical evaluation and cross‐sectional imaging modalities such as ultrasound and computed tomography for patients with suspected colonic diverticulitis and to determine the value of these examinations in clinical decision‐making.

Method  A prospective analysis was conducted of 802 consecutive patients that presented with abdominal pain at the emergency department. Initial clinical diagnoses and management proposals were compared to the final diagnoses and therapeutic strategies for all patients.

Results  Fifty‐seven patients were identified with colonic diverticulitis as the final diagnosis. The positive and negative predictive values for the clinical diagnosis of colonic diverticulitis were 0.65 and 0.98 respectively. Additional cross‐sectional imaging had a positive and negative predictive value of respectively 0.95 and 0.99 or higher. These additional examinations led to a correct change of the initial clinical diagnosis in 37% of the patients, and a change in management in only 7%.

Conclusion  The accuracy of the clinical diagnosis for colonic diverticulitis is low. Ultrasound and computed tomography have superior diagnostic accuracy but these examinations rarely change the initial management proposal.
A study of the functional aberration of the pouch in anorectal malformation associated with congenital pouch colon
Authors: Gangopadhyay A. N. , Pandey A. , Rastogi N. , Mandal M. B. , Gopal S. C. , Gupta D. K. , Srivastava A.
Published: January 2009

Objective There are noin vitrostudies of congenital pouch colon (CPC) associated with anorectal malformation (ARM) to understand its mechanism of contractility. There is no consensus regarding the utilization of the CPC in repair of anorectal malformation. In view of the above, it was decided to carry out detailedin vitrophysiological study of the excised CPC.

Method The excised specimens of CPC were taken and 15‐ to 20‐mm long both longitudinal and transverse strips of muscle were obtained both from the proximal and distal part. Contraction was recorded using softwarechart‐5for windows. Drugs used were acetylcholine, histamine, adrenaline, atropine and pheniramine maleate. The amplitude of contractions was converted to tension gram and then the tension so developed was expressed as tension per unit mass (per gram of wet tissue).

Results There were total of 21 specimens of high ARM with CPC. Five specimens were of the complete pouch, which did not show a response to any drug and the remaining 16 had an incomplete pouch. The mean longitudinal and circular muscle contractions of these 16 samples were statistically higher for the proximal segment than the distal segment both for acetylcholine and histamine. The effect of atropine was not significant but that of adrenaline and pheniramine maleate were significant on the distal segment muscle.

Conclusion Congenital pouch colon being deficient or having poorly developed receptors in their wall can not function properly as a reservoir for faeces and, hence, it should be excised to allow adequate function.
Enhanced recovery programmes and colorectal surgery: does the laparoscope confer additional advantages?
Authors: Khan S. , Gatt M. , MacFie J.
Published: January 2009

Background  Enhanced recovery after surgery (ERAS) protocols aim to reduce postoperative lengths of stay (LOS). Laparoscopic surgery shares the same objective. Whether or not laparoscopic surgery conveys additional benefits over and above those achievable with ERAS alone is unclear.

Method  A review of the literature from January 1966 to June 2008 was performed. Randomized trial and case series investigating the role of laparoscopic surgery within ERAS protocols were included. These were assessed for LOS, readmissions, return of gut function, quality of life and cost of treatment.

Results  Four publications from three randomized trials and another seven case series were identified. Two randomized trials revealed no difference in the LOS and readmission rates between ERAS when used alone and ERAS with the inclusion of laparoscopic surgery. However, a third trial revealed a significantly shorter LOS and a lower readmission rate in the ERAS and laparoscopic group.

Conclusion  The limited evidence presently available suggests that no further benefit is obtained by the inclusion of laparoscopic surgery in ERAS protocols. Further research is needed to derive more definitive conclusions.
A Picture of the Floating World: Grounding the Secessionary Affluence of the Residential Cruise Liner
Authors: Atkinson Rowland , Blandy Sarah
Published: January 2009

Abstract:  A quarter century of financial deregulation, robber‐baron corporatism and growing income polarisation has enabled the spatial partitioning of urban space into new and complex arrangements of micro‐neighbourhood governance and privatism. These archipelagos of fortress homes and neighbourhoods increasingly lie outside the spaces of conventional state and city government. Yet while residential spaces of urban affluence have been unable to fully remove contact with the social diversity of the public realm, nomadic forms of super‐affluence, flowing around a global–national urban system, have generated a form of networked extra‐territoriality—a social space decoupled from the perceived risks and general dowdiness of the social world beneath it. This paper examines this space via the curious case of The World, a large residential cruise ship which, as its name suggests, roams the oceans and ports of the globe. Our title is taken from the name given to Japanese paintings of the new affluence and fantasy of life lived by the affluent and artists in late nineteenth century Japanese cities (O Ukiyo E, or pictures of the floating world). We suggest that The World forms a similarly disconnected realm, not only literally afloat, also detached from the reality of a world that has been strategically left behind.
On the verge of something extraordinary
Authors: Prahalad C.K. , Dearlove Des
Published: January 2009

According to the global guru ranking, the Thinkers 50, published by The Times, C.K. Prahalad is “the most influential living business thinker in the world”. Prahalad believes that business leaders need to start thinking about their marketplace as all six billion people on the planet. Des Dearlove talked to him about his latest thinking and how it was influenced by his early years in India.
Mapping multinational operations
Authors: Birnik Andreas , Moat Richard
Published: January 2009

Andreas Birnik and Richard Moat assert that multinational firms need to develop an operating model at the activity level. By doing so, managers can identify inconsistencies and develop coherent operations across local subsidiaries, the corporate centre and outsourcing partners.
Diagnosis at a distance: the invisible work of patients and healthcare professionals in cardiac telemonitoring technology
Authors: Oudshoorn Nelly
Published: January 2009

Although patients are often absent in discourses on telemedicine, many telemonitoring applications constitute a new medical practice in which patients are expected to play an active role. The paper is based on a study of the use of one specific telemonitoring device, an ambulatory ECG recorder introduced to diagnose infrequent irregularities of the heart rhythm. It seeks to examine all the invisible work it takes to produce patients who are active and responsible as participants in the diagnosis of their heart problem. In particular, I address the question of how we can understand that individuals who are anxious about their heart function manage to adopt the role of ‘diagnostic agent’. This research shows that, although many patients managed to become competent users of the new technology, there are important patterns of selective use patients invented to integrate the technology in their daily life. In conclusion, the paper suggests that most patients were able to adopt the role of diagnostic agent not only because of their individual motivation but because of their location in the socio‐technical network of this technology, in which the invisible work of home‐care nurses and physicians at the telemedical centre made all the difference.