bluuebunny/crossref_metadata_2025 huggingface dataset:
Handmade outer flushing channel for safe endoscopic submucosal dissection
Authors: Hirasawa Dai , Fujita Naotaka , Ishida Kazuhiko , Matsunaga Atsuo , Senoo Shigeharu , Yonechi Makoto , Suzuki Takashi , Sugawara Toshiki
Published: March 2005

Endoscopic submucosal dissection (ESD) is rapidly becoming widespread as an excellent method for the treatment of intramucosal tumors, especially the superficially spreading type, of the digestive tract. In contrast, of great concern are the complications that may arise when the procedure is prolonged due to such factors as bleeding during mucosal cutting and submucosal dissection. To realize safe performance of ESD, we have developed and have been using a handmade outer channel for flushing with excellent results. Mounting the outer channel for flushing provides an effective flushing function without costly investment and contributes to maintaining a clear endoscopic view during the procedure. This device enables some extended indications for endoscopic procedures, including hemostasis of hemorrhagic peptic ulcers and rupture of esophagogastric varices.
A case of CA19‐9‐producing adenocarcinoma of the remnant stomach resembling gastritis cystica polyposa
Authors: Tahara Hiroki , Hayashi Shigeyuki , Kusano Motoyasu , Kojima Masaru , Ohki Ichiro
Published: March 2005

Gastritis cystica polyposa (GCP) is a well‐known precancerous lesion of the remnant stomach. We report a case of carbohydrate antigen (CA) 19–9‐producing well‐differentiated adenocarcinoma of the remnant stomach that resembled GCP. The patient was a 66‐year‐old Japanese man who had undergone subtotal gastrectomy 20 years previously. The tumor developed in the remnant stomach at the anastomotic line. Histologically, the lesion completely encircled the gastroenterostomy stoma. There was florid growth of glands with cystic dilatation and minimal atypia extending through the thickened muscularis propria into the subserosa. Small foci of less well‐differentiated adenocarcinoma were also detected, including irregular glands or small clusters of mucus‐producing cells with moderate atypia. Immunostaining revealed that numerous tumor cells were positive for carcinoembryonic antigen and CA19‐9, whereas only a few cells were positive for p53. The macroscopic, histopathological and immunohistochemical findings indicated a diagnosis of CA19‐9‐producing well‐differentiated adenocarcinoma of the remnant stomach. To avoid underdiagnosis, careful attention should be paid to the above‐mentioned morphological features and immunohistochemical findings, in addition to the endoscopic findings.
Predictors of a response to cyclosporine or leukocyte removal therapy in patients with refractory ulcerative colitis
Authors: Ando Takafumi , Watanabe Osamu , Furuta Ryuichi , Maeda Osamu , Nishio Yuji , Nishiwaki Tsuyoshi , Ina Kenji , Kusugami Kazuo , Goto Hidemi
Published: March 2005

Introduction: Despite decades of clinical experience in optimizing the induction and maintenance of remission in patients with ulcerative colitis (UC), some patients remain refractory to conventional medical treatment while, in others, the effectiveness of drugs is limited by side‐effects. We investigated factors predictive of the efficacy of cyclosporine and leukocyte removal therapy in patients with intractable UC.

Methods: Forty‐five patients with moderate to severe UC who were refractory to corticosteroid therapy were enrolled. Twenty‐six patients were treated with cyclosporine and 19 by leukocyte removal therapy. Disease activity index (DAI) score assessment, and colonoscopic and histological examinations were done before and at 10, 20 and 40 days after the initiation of treatment. A clinical response to treatment was defined as a decrease in DAI score of 3 points or more at 40 days.

Results: Responder ratio did not significantly differ between the cyclosporine (65.6%) and leukocyte removal therapy (63.2%) groups. Factors predictive of a response to cyclosporine therapy were fever (≥ 38.0°C), anemia and large mucosal ulceration. In contrast, mucosal bleeding and poor extensibility of the intestinal lumen were predictive of a poor response to cyclosporine. No significant differences in any clinical or endoscopic parameter predictive of a response to leukocyte removal therapy were identified.

Conclusions: Intravenous cyclosporine may be effective in patients who have severe steroid‐refractory UC, and leukocyte removal therapy may be useful in patients with moderate active UC predicted to be refractive to cyclosporine.
Bi‐hemispheric contribution to functional motor recovery of the affected forelimb following focal ischemic brain injury in rats
Authors: Biernaskie Jeff , Szymanska Aleksandra , Windle Victoria , Corbett Dale
Published: March 2005

In many recovering hemiparetic stroke patients, movement of the affected limb elicits ipsilateral activation of sensorimotor areas within the undamaged hemisphere, which is not observed in control subjects. Following middle cerebral artery occlusion, rats received intensive enriched‐rehabilitation (ER) of the impaired forelimb for 4 weeks. Weekly assessments on a skilled reaching test demonstrated significant improvement in ischemic animals over 4 weeks of ER (P < 0.05). We hypothesized that if the undamaged forelimb motor cortex contributed to improved forelimb function, then inhibition of neural activity within this region should reinstate (at least some of) the initial motor impairment. After 3 and 4 weeks of ER, animals received a microinjection of lidocaine hydrochloride into the undamaged motor cortex and were re‐assessed on reaching ability. The behavioral effect of lidocaine challenge was dependent on the size of the infarct: animals with large infarcts were rendered unable to retrieve any food pellets and had great difficulty even contacting a pellet with the affected forepaw. Small‐infarct animals were only moderately affected (25% reduction in success) by lidocaine, an effect similar to that observed in control animals. Qualitative assessments of recovered reaching after 4 weeks of rehabilitation revealed that impairments in forelimb lift, advance and aim were exacerbated (P < 0.05) following lidocaine‐inactivation of the undamaged motor cortex of animals with large ischemic infarcts. In animals with small infarcts, lidocaine challenge only impaired limb advance. Thus, recruitment of the undamaged hemisphere may depend on the functional integrity of the remaining sensorimotor system. These data suggest that, in the rat, the undamaged (ipsilateral) motor system may contribute to compensatory recovery of the affected forelimb.
α‐Amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate receptor autoradiography in mouse brain after single and repeated withdrawal from diazepam
Authors: Allison C. , Pratt J. A. , Ripley T. L. , Stephens D. N.
Published: March 2005

Withdrawal from chronic treatment with benzodiazepines is associated with increased neuronal excitability leading to anxiety, aversive effects and increased seizure sensitivity. After repeated withdrawal experiences, seizure sensitivity increases while withdrawal‐induced anxiety and aversion decrease. We used autoradiographical methods employing [3H]Ro48 8587, a selective ligand for glutamatergic α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate (AMPA) receptors, to study withdrawal‐induced changes in AMPA receptor binding in areas of the mouse brain postulated to be involved in these responses. Mice were given 21 days treatment with diazepam (15 mg/kg, s.c. in sesame oil) followed by withdrawal (single withdrawal) or three blocks of 7 days treatment interspersed with 3‐day periods to allow washout of drug (repeated withdrawal). In keeping with heightened excitability in withdrawal from chronic diazepam treatment, the single withdrawal group showed, 72 h after their final dose of diazepam, increased [3H]Ro48 8587 binding in several brain areas associated with emotional responses or seizure activity, including hippocampal subfields, amygdalar and thalamic nuclei and motor cortex. In contrast, the repeated withdrawal group showed no changes in [3H]Ro48 8587 binding in any brain area studied. These observations are consistent with up‐regulation of AMPA receptor‐mediated transmission being important in withdrawal‐induced anxiety and aversion but not in increased seizure sensitivity associated with repeated withdrawal. As changes in AMPA receptor subunit expression alter the functionality of the receptor, future studies will address this possibility.
SHORT COMMUNICATIONS: Semantic memory retrieval: cortical couplings in object recognition in the N400 window
Authors: Supp Gernot G. , Schlögl Alois , Fiebach Christian J. , Gunter Thomas C. , Vigliocco Gabriella , Pfurtscheller Gert , Petsche Hellmuth
Published: March 2005

To characterize the regional changes in neuronal couplings and information transfer related to semantic aspects of object recognition in humans we used partial‐directed EEG‐coherence analysis (PDC). We examined the differences of processing recognizable and unrecognizable pictures as reflected by changes in cortical networks within the time‐window of a determined event‐related potential (ERP) component, namely the N400. Fourteen participants performed an image recognition task, while sequentially confronted with pictures of recognizable and unrecognizable objects. The time‐window of N400 as indicative of object semantics was defined from the ERP. Differences of PDC in the beta‐band between these tasks were represented topographically as patterns of electrical couplings, possibly indicating changing degrees of functional cooperation between brain areas. Successful memory retrieval of picture meaning appears to be supported by networks comprising left temporal and parietal regions and bilateral frontal brain areas.
Differential effects of forskolin on tyrosine hydroxylase gene transcription in identified brainstem catecholaminergic neuronal subtypes in organotypic culture
Authors: Rusnak Milan , Gainer Harold
Published: March 2005

The regulation of gene expression of tyrosine hydroxylase (TH), the rate‐limiting enzyme in catecholamine synthesis, was studied in brainstem noradrenergic nuclei, locus coeruleus (LC), A2 and A1, in vitro. Several novel experimental approaches employed in this study included: (i) the development of a slice‐explant model in which these brainstem nuclei maintained a high survival of the noradrenergic neurons, an organotypic topology and the coexpression of two identifying markers in addition to TH, i.e. norepinephrine transporter (NET) and vesicular monoamine transporter 2 (VMAT2); (ii) quantitative analysis of TH transcription in these nuclei was made using a labelled intronic probe to measure TH heteronuclear RNA (hnRNA) and (iii) the use of tetrodotoxin in the media to eliminate spontaneous neural activity in these nuclei, thereby providing a basal state as the starting point for the study of TH transcription under various pharmacological perturbations. In the presence of TTX, the adenylcyclase stimulator, forskolin, produced a 155% increase in LC, a 130% increase in A1, and a 220% increase in A2 in TH hnRNA as compared to control nuclei. This effect of forskolin was abolished in the LC and A1 by the PKA inhibitor, H89 (5 µm), but not by the MAP kinase pathway (MEK) inhibitor, PD98059 (75 µm). In contrast, the robust increase in TH transcription produced by forskolin in A2 neurons, was completely inhibited by PD98059, and only partially inhibited by H89, showing that induced TH transcription is mediated by different kinase pathways in specific central noradrenergic neuronal subtypes.
Attending to visual or auditory motion affects perception within and across modalities: an event‐related potential study
Authors: Beer Anton L. , Röder Brigitte
Published: March 2005

The present event‐related potential (ERP) study examined the role of dynamic features in multisensory binding. It was tested whether endogenous attention to the direction of motion affects processing of visual and auditory stimuli within and across modalities. Human participants perceived horizontally moving dot patterns and sounds that were presented either continuously (standards) or briefly interrupted (infrequent deviants). Their task was to detect deviants moving in a particular direction within a primary modality, but to detect all deviants irrespective of their motion direction within the secondary modality. Attending to the direction of visual motion resulted in a broad selection negativity (SN) starting at about 200 ms post‐stimulus onset, and attending to the direction of auditory motion resulted in a positive difference wave at 150 ms that was followed by a broad negativity starting at about 200 ms (unimodal effects). Moreover, dot patterns moving in a direction that was attended within audition were detected faster and more accurately than oppositely moving stimuli and elicited a cross‐modal SN wave. Corresponding cross‐modal behavioural and ERP results were obtained for sounds moving in a direction that was attended within vision. Unimodal and cross‐modal ERP attention effects partially differed in their scalp topography. The present study shows that dynamic features (direction of motion) may be used to link input across modalities and demonstrates for the first time that these multisensory interactions take place as early as about 200 ms after stimulus onset.
Exposure to pulse‐modulated radio frequency electromagnetic fields affects regional cerebral blood flow
Authors: Huber R. , Treyer V. , Schuderer J. , Berthold T. , Buck A. , Kuster N. , Landolt H. P. , Achermann P.
Published: March 2005

We investigated the effects of radio frequency electromagnetic fields (RF EMF) similar to those emitted by mobile phones on waking regional cerebral blood flow (rCBF) in 12 healthy young men. Two types of RF EMF exposure were applied: a ‘base‐station‐like’ and a ‘handset‐like’ signal. Positron emission tomography scans were taken after 30 min unilateral head exposure to pulse‐modulated 900 MHz RF EMF (10 g tissue‐averaged spatial peak‐specific absorption rate of 1 W/kg for both conditions) and sham control. We observed an increase in relative rCBF in the dorsolateral prefrontal cortex on the side of exposure. The effect depended on the spectral power in the amplitude modulation of the RF carrier such that only ‘handset‐like’ RF EMF exposure with its stronger low‐frequency components but not the ‘base‐station‐like’ RF EMF exposure affected rCBF. This finding supports our previous observation that pulse modulation of RF EMF is necessary to induce changes in the waking and sleep EEG, and substantiates the notion that pulse modulation is crucial for RF EMF‐induced alterations in brain physiology.
Somatodendritic autoreceptor regulation of serotonergic neurons: dependence on l‐tryptophan and tryptophan hydroxylase‐activating kinases
Authors: Liu Rong‐Jian , Lambe Evelyn K. , Aghajanian George K.
Published: March 2005

The somatodendritic 5‐HT1A autoreceptor has been considered a major determinant of the output of the serotonin (5‐HT) neuronal system. However, recent studies in brain slices from the dorsal raphe nucleus have questioned the relevance of 5‐HT autoinhibition under physiological conditions. In the present study, we found that the difficulty in demonstrating 5‐HT tonic autoinhibition in slice results from in vitro conditions that are unfavorable for sustaining 5‐HT synthesis. Robust, tonic 5‐HT1A autoinhibition can be restored by reinstating in vivo 5‐HT synthesizing conditions with the initial 5‐HT precursor l‐tryptophan and the tryptophan hydroxylase co‐factor tetrahydrobiopterin (BH4). The presence of tonic autoinhibition under these conditions was revealed by the disinhibitory effect of a low concentration of the 5‐HT1A antagonist WAY 100635. Neurons showing an autoinhibitory response to l‐tryptophan were confirmed immunohistochemically to be serotonergic. Once conditions for tonic autoinhibition had been established in raphe slice, we were able to show that 5‐HT autoinhibition is critically regulated by the tryptophan hydroxylase‐activating kinases calcium/calmodulin protein kinase II (CaMKII) and protein kinase A (PKA). In addition, at physiological concentrations of l‐tryptophan, there was an augmentation of 5‐HT1A receptor‐mediated autoinhibition when the firing of 5‐HT cells activated with increasing concentrations of the α1 adrenoceptor agonist phenylephrine. Increased calcium influx at higher firing rates, by activating tryptophan hydroxylase via CaMKII and PKA, can work together with tryptophan to enhance negative feedback control of the output of the serotonergic system.
Anterior perirhinal cortex kindling produces long‐lasting effects on anxiety and object recognition memory
Authors: Hannesson D. K. , Howland J. G. , Pollock M. , Mohapel P. , Wallace A. E. , Corcoran M. E.
Published: March 2005

Temporal lobe epilepsy (TLE) is frequently accompanied by memory impairments and, although their bases are unknown, most research has focused on the hippocampus. The present study investigated the importance of another medial temporal lobe structure, the perirhinal cortex (Prh), in changes in memory in TLE using kindling as a model. Rats were kindled twice daily with anterior Prh stimulation until three fully generalized seizures were evoked. Beginning 7 days later and on successive days, rats were tested in an elevated plus maze, a large circular open field, an open field object exploration task and a delayed‐match‐to‐place task in a water maze in order to assess anxiety‐related and exploratory behaviour, object recognition memory and spatial cognition. Kindling increased anxiety‐related behaviour in both the elevated plus and open field mazes and disrupted spontaneous object recognition but spared all other behaviours tested. These results are consistent with other findings indicating a greater role for the Prh in object memory and emotional behaviour than in spatial memory and contrast with the selective disruption of spatial memory produced by dorsal hippocampal kindling. The site‐selectivity of the behavioural disruptions produced by kindling indicates that such effects are probably mediated by changes particular to the site of seizure initiation rather than to changes in the characteristic circuitry activated by limbic seizure generalization. Further investigation of the behavioural effects of Prh kindling may be useful for studying the mechanisms of mnemonic and affective dysfunction associated with TLE and offer insights into bases for variability in such dysfunction across patients.
19‐Nortestosterone influences neural stem cell proliferation and neurogenesis in the rat brain
Authors: Brännvall Karin , Bogdanovic Nenad , Korhonen Laura , Lindholm Dan
Published: March 2005

Abuse of androgenic anabolic steroids can affect brain function leading to behavioural changes. In this study, the effects of the testosterone analogue, 19‐nortestosterone, on rat neural stem cells was examined. The androgen receptor is expressed by cultured embryonic and adult neural stem cells, and is also present in the ventricular epithelium during development and in the adult brain in, among others, dentate gyrus. In neural stem cells stimulated with epidermal growth factor, nandrolone reduced cell proliferation, especially in adult ones. The decrease was abolished by flutamide, a receptor antagonist. Nandrolone also decreased the BrdU labelling of neural stem cells in the dentate gyrus, demonstrating an effect of the hormone on cell proliferation in vivo. The effect of nandrolone was observed with both female and male rats but it was more pronounced in pregnant rats, indicating an involvement of oestrogen in nandrolone action. Nandrolone also decreased the number of newly born neuronal cells in the dentate gyrus of male rats. The results show that nandrolone has important effects on the proliferation and differentiation of neural stem cells expressing the cognate androgen receptor. The data show that the use of nandrolone may severely affect the formation of neural stem cells and could therefore have long‐term negative consequences in the brain.
Flight into Security: A New Approach and Measure of the Authoritarian Personality
Authors: Oesterreich Detlef
Published: March 2005

A basic pattern of human response to stressful and uncertain situations which provoke anxiety and insecurity is to seek security and shelter. Those who provide support become by a process of psychological attribution authorities. Therefore the mechanism of seeking support and shelter under strained conditions might be called an “authoritarian reaction.” Socialization involves a negotiation with this basic reaction of flight in situations of uncertainty. As individuals develop, they learn to overcome the authoritarian reaction by formulating their own strategies to cope with reality. The authoritarian personality emerges out of an inability to generate such individual coping strategies. Authoritarian personalities defer to the dictates and control of others who offer them the certainty and comfort they cannot provide for themselves. Extensions of this basic authoritarian response are the rejection of the new and the unfamiliar, rigid adherence to norms and value systems, an anxious and inflexible response to new situations, suppressed hostility, and passive aggression. A new measure based on items on one's own behavior, feelings, motivation, and the individual's concept of the self was developed and tested in several empirical studies. It obtained a good reliability and proved to be valid by correlating to measures of right‐wing extremism, negative attitudes toward immigrants and women.
Bayesian Classification of Tumours by Using Gene Expression Data
Authors: Mallick Bani K. , Ghosh Debashis , Ghosh Malay
Published: March 2005

Precise classification of tumours is critical for the diagnosis and treatment of cancer. Diagnostic pathology has traditionally relied on macroscopic and microscopic histology and tumour morphology as the basis for the classification of tumours. Current classification frameworks, however, cannot discriminate between tumours with similar histopathologic features, which vary in clinical course and in response to treatment. In recent years, there has been a move towards the use of complementary deoxyribonucleic acid microarrays for the classi-fication of tumours. These high throughput assays provide relative messenger ribonucleic acid expression measurements simultaneously for thousands of genes. A key statistical task is to perform classification via different expression patterns. Gene expression profiles may offer more information than classical morphology and may provide an alternative to classical tumour diagnosis schemes. The paper considers several Bayesian classification methods based on reproducing kernel Hilbert spaces for the analysis of microarray data. We consider the logistic likelihood as well as likelihoods related to support vector machine models. It is shown through simulation and examples that support vector machine models with multiple shrinkage parameters produce fewer misclassification errors than several existing classical methods as well as Bayesian methods based on the logistic likelihood or those involving only one shrinkage parameter.
PAYING FOR CROSSRAIL : THE BUSINESS CASE
Authors: Schabas Michael
Published: March 2005

A new railway is being planned across London. Incremental fares revenue will only pay about a quarter of the £10 billion1 expected cost, so the Greater London Assembly (GLA) is considering ‘alternative funding mechanisms’. These include new taxes on businesses that are presumed to benefit from the scheme. Taxes would deter the very investment Crossrail is supposed to support. The GLA would do better to change the scheme to reduce the need for subsidy and strengthen the business case.
EQUAL TREATMENT DIRECTIVE MISUNDERSTANDS RISK AND THREATENS INSURANCE MARKETS
Authors: MacDonnell Paul
Published: March 2005

The Equal Treatment Directive, which will come into force on 21 December 2007, aims to outlaw‘discrimination’ between men and women in the calculation of insurance premiums, is founded upon a fallacious understanding of the nature of actuarial calculations and the morality of‘discriminatory’ calculations where state provision of insurance has traditionally been ‘non‐discriminatory’. The Equal Treatment Directive will have perverse consequences contrary to the aims of its creators ‐ benefiting the better‐off at the expense of the poor and, in some circumstances, men at the expense of women ‐ and will also threaten the private provision of pensions and healthcare essential to solving the looming pensions and healthcare funding crisis among EU member states.
Activation of Akt/PKB, increased phosphorylation of Akt substrates and loss and altered distribution of Akt and PTEN are features of Alzheimer's disease pathology
Authors: Griffin Rebecca J. , Moloney Aileen , Kelliher Mary , Johnston Janet A , Ravid Rivka , Dockery Peter , O'Connor Rosemary , O'Neill Cora
Published: March 2005

Studies suggest that activation of phosphoinositide 3‐kinase‐Akt may protect against neuronal cell death in Alzheimer's disease (AD). Here, however, we provide evidence of increased Akt activation, and hyperphosphorylation of critical Akt substrates in AD brain, which link to AD pathogenesis, suggesting that treatments aiming to activate the pathway in AD need to be considered carefully. A different distribution of Akt and phospho‐Akt was detected in AD temporal cortex neurons compared with control neurons, with increased levels of active phosphorylated‐Akt in particulate fractions, and significant decreases in Akt levels in AD cytosolic fractions, causing increased activation of Akt (phosphorylated‐Akt/total Akt ratio) in AD. In concordance, significant increases in the levels of phosphorylation of total Akt substrates, including: GSK3βSer9, tauSer214, mTORSer2448, and decreased levels of the Akt target, p27kip1, were found in AD temporal cortex compared with controls. A significant loss and altered distribution of the major negative regulator of Akt, PTEN (phosphatase and tensin homologue deleted on chromosome 10), was also detected in AD neurons. Loss of phosphorylated‐Akt and PTEN‐containing neurons were found in hippocampal CA1 at end stages of AD. Taken together, these results support a potential role for aberrant control of Akt and PTEN signalling in AD.
TheCaenorhabditis elegans lev‐8gene encodes a novel type of nicotinic acetylcholine receptor α subunit
Authors: Towers Paula R. , Edwards Ben , Richmond Janet E. , Sattelle David B.
Published: March 2005

We have clonedCaenorhabditis elegans lev‐8and demonstrated that it encodes a novel nicotinic acetylcholine receptor (nAChR) subunit (previously designated ACR‐13), which has functional roles in body wall and uterine muscles as part of a levamisole‐sensitive receptor. LEV‐8 is an α subunit and is the first to be described from the ACR‐8‐like group, a new class of nAChR with atypical acetylcholine‐binding site (loop C) and channel‐lining motifs. A single base pair change in the first intron oflev‐8inlev‐8(x15)mutants leads to alternative splicing and the introduction of a premature stop codon.lev‐8(x15)worms are partially resistant to levamisole‐induced egg laying and paralysis, phenotypes rescued by expression of the wild‐type gene.lev‐8(x15)worms also show reduced rates of pharyngeal pumping. Electrophysiological recordings from body wall muscle show that currents recorded in response to levamisole have reduced amplitude inlev‐8(x15)compared with wild‐type animals. Consistent with these phenotypic observations, green fluorescent protein fused to LEV‐8 is expressed in body wall and uterine muscle, motor neurons and epithelial‐derived socket cells. Thus, LEV‐8 is a levamisole receptor subunit and exhibits the most diverse expression pattern of any invertebrate nAChR subunit studied to date.
Antioxidant responses to chronic hypoxia in the rat cerebellum and pons
Authors: Ramanathan Lalini , Gozal David , Siegel Jerome M.
Published: March 2005

Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia (CIH) and sleep fragmentation and deprivation. Exposure to CIH results in oxidative stress in the cortex, hippocampus and basal forebrain of rats and mice. We show that sustained and intermittent hypoxia induces antioxidant responses, an indicator of oxidative stress, in the rat cerebellum and pons. Increased glutathione reductase (GR) activity and thiobarbituric acid reactive substance (TBARS) levels were observed in the pons and cerebellum of rats exposed to CIH or chronic sustained hypoxia (CSH) compared with room air (RA) controls. Exposure to CIH or CSH increased GR activity in the pons, while exposure to CSH increased the level of TBARS in the cerebellum. The level of TBARS was increased to a greater extent after exposure to CSH than to CIH in the cerebellum and pons. Increased superoxide dismutase activity (SOD) and decreased total glutathione (GSHt) levels were observed after exposure to CIH compared with CSH only in the pons. We have previously shown that prolonged sleep deprivation decreased SOD activity in the rat hippocampus and brainstem, without affecting the cerebellum, cortex or hypothalamus. We therefore conclude that sleep deprivation and hypoxia differentially affect antioxidant responses in different brain regions.
Specific interaction of VEGF165 with β‐amyloid, and its protective effect on β‐amyloid‐induced neurotoxicity
Authors: Yang Seung‐Pil , Kwon Byoung‐Oh , Gho Yong Song , Chae Chi‐Bom
Published: March 2005

β‐amyloid (Aβ) is a major component of senile plaques that is commonly found in the brain of Alzheimer's disease (AD) patient. In the previous report, we showed that an important angiogenic factor, vascular endothelial growth factor (VEGF) interacts with Aβ and is accumulated in the senile plaques of AD patients' brains. Here we show that Aβ interacts with VEGF165 isoform, but not with VEGF121. Aβ binds to the heparin‐binding domain (HBD) of VEGF165 with similar affinity as that of intact VEGF165. Aβ binds mostly to the C‐terminal subdomain of HBD, but with greatly reduced affinity than HBD. Therefore, the full length of HBD appears to be required for maximal binding of Aβ. Although Aβ binds to heparin‐binding sequence of VEGF, it does not bind to other heparin‐binding growth factors except midkine. Thus it seems that Aβ recognizes unique structural features of VEGF HBD. VEGF165 prevents aggregation of Aβ through its HBD. We localized the core VEGF binding site of Aβ at around 26–35 region of the peptide. VEGF165 and HBD protect PC12 cells from the Aβ‐induced cytotoxicity. The mechanism of protection appears to be inhibition of both Aβ‐induced formation of reactive oxygen species and Aβ aggregation.
Selective gene silencing of rat ATP‐binding cassette G2 transporter in an in vitro blood–brain barrier model by short interfering RNA
Authors: Hori Satoko , Ohtsuki Sumio , Ichinowatari Masashi , Yokota Takanori , Kanda Takashi , Terasaki Tetsuya
Published: March 2005

The aim of the present study was to specifically silence the rat ATP‐binding cassette transporter G2 (rABCG2) gene in brain capillary endothelial cells by transfection of short interfering RNA (siRNA). Four different siRNAs designed to target rABCG2 were each transfected into HEK293 cells with myc‐tagged rABCG2 cDNA. Quantitative real‐time PCR and western blot analyses revealed that three of the siRNAs were able to reduce exogenous rABCG2 mRNA and protein levels in HEK293 cells. Moreover, rABCG2‐mediated mitoxantrone efflux transport was suppressed by the introduction of these three siRNAs into HEK293 cells. In contrast, the other siRNA and non‐specific control siRNA did not significantly affect the mRNA expression, the protein level or the transport activity. Endogenous rABCG2 mRNA and protein expression in a conditionally immortalized rat brain capillary endothelial cell line (TR‐BBB13) was suppressed by the most potent siRNA among the four siRNAs tested. Furthermore, this siRNA did not affect the mRNA levels of other ABC transporters, such as ABCB1, ABCC1 and ABCG1, and the protein level of ABCB1 in TR‐BBB13 cells, suggesting that it can selectively silence rABCG2 at the blood–brain barrier. This should be a useful and novel strategy for clarifying the contribution of rABCG2 to brain‐to‐blood transport of substrate drugs and endogenous compounds across the blood–brain barrier.
A chemically modified preparation of α2‐macroglobulin binds β‐amyloid peptide with increased affinity and inhibits Aβ cytotoxicity
Authors: Mettenburg Joseph M. , Arandjelovic Sanja , Gonias Steven L.
Published: March 2005

Macromolecules that bind β‐amyloid peptide (Aβ) and neutralize Aβ cytotoxicity offer a promising new approach for treating Alzheimer's disease. When the plasma protein, α2‐macroglobulin (α2M), is treated with methylamine (α2M‐MA), it undergoes conformational change and acquires Aβ‐binding activity. In this study, we demonstrate that a chemically stabilized preparation of human α2M conformational intermediates (α2M‐cis‐Pt/MA) binds Aβ with greatly increased affinity, compared with α2M‐MA. α2M‐cis‐Pt/MA was generated by reacting α2M with the protein cross‐linking reagent, cis‐Pt, followed by methylamine. Increased Aβ‐binding to α2M‐cis‐Pt/MA was demonstrated by co‐migration of radio‐iodinated proteins in non‐denaturing PAGE, chemical cross‐linking, and co‐immunoprecipitation. The apparent KD for Aβ‐binding to α2M‐cis‐Pt/MA was decreased 10‐fold, compared with α2M‐MA, to 29 nm. Native α2M demonstrated negligible Aβ‐binding, as anticipated. α2M‐cis‐Pt/MA markedly counteracted Aβ‐induced C6 cell apoptosis. Essentially complete inhibition of apoptosis was observed even when the Aβ was present at fourfold molar excess to α2M‐cis‐Pt/MA. Under equivalent conditions, α2M‐MA inhibited apoptosis by 25 ± 6%. When Aβ and α2M‐cis‐Pt/MA were added to human plasma in vitro, significant binding was detected. No binding was observed when an equivalent concentration of native α2M or α2M‐MA was added to plasma. We propose that α2M‐cis‐Pt/MA is a novel alternative to Aβ‐specific antibodies, for studying the efficacy of Aβ‐binding agents in vitro and in vivo.
Extracellular signal‐regulated kinase 1/2 mediates survival, but not axon regeneration, of adult injured central nervous system neurons in vivo
Authors: Pernet Vincent , Hauswirth William W. , Di Polo Adriana
Published: March 2005

Neurotrophins play important roles in the response of adult neurons to injury. The intracellular signaling mechanisms used by neurotrophins to regulate survival and axon growth in the mature CNS in vivo are not well understood. The goal of this study was to define the role of the extracellular signal‐regulated kinases 1/2 (Erk1/2) pathway in the survival and axon regeneration of adult rat retinal ganglion cells (RGCs), a prototypical central neuron population. We used recombinant adeno‐associated virus (AAV) to selectively transduce RGCs with genes encoding constitutively active or wild‐type mitogen‐activated protein kinase kinase 1 (MEK1), the upstream activator of Erk1/2. In combination with anterograde and retrograde tracing techniques, we monitored neuronal survival and axon regeneration in vivo. MEK1 gene delivery led to robust and selective transgene expression in multiple RGC compartments including cell bodies, dendrites, axons and targets in the brain. Furthermore, MEK1 activation induced in vivo phosphorylation of Erk1/2 in RGC bodies and axons. Quantitative analysis of cell survival demonstrated that Erk1/2 activation promoted robust RGC neuroprotection after optic nerve injury. In contrast, stimulation of the Erk1/2 pathway was not sufficient to induce RGC axon growth beyond the lesion site. We conclude that the Erk1/2 pathway plays a key role in the survival of axotomized mammalian RGCs in vivo, and that activation of other signaling components is required for axon regeneration in the growth inhibitory CNS environment.
Striatal glutamate release evoked in vivo by NMDA is dependent upon ongoing neuronal activity in the substantia nigra, endogenous striatal substance P and dopamine
Authors: Marti Matteo , Manzalini Massimiliano , Fantin Martina , Bianchi Clementina , Della Corte Laura , Morari Michele
Published: March 2005

The aim of the present microdialysis study was to investigate whether the increase in striatal glutamate levels induced by intrastriatal perfusion with NMDA was dependent on the activation of extrastriatal loops and/or endogenous striatal substance P and dopamine. The NMDA‐evoked striatal glutamate release was mediated by selective activation of the NMDA receptor‐channel complex and action potential propagation, as it was prevented by local perfusion with dizocilpine and tetrodotoxin, respectively. Tetrodotoxin and bicuculline, perfused distally in the substantia nigra reticulata, prevented the NMDA‐evoked striatal glutamate release, suggesting its dependence on ongoing neuronal activity and GABAA receptor activation, respectively, in the substantia nigra. The NMDA‐evoked glutamate release was also dependent on striatal substance P and dopamine, as it was antagonized by intrastriatal perfusion with selective NK1 (SR140333), D1‐like (SCH23390) and D2‐like (raclopride) receptor antagonists, as well as by striatal dopamine depletion. Furthermore, impairment of dopaminergic transmission unmasked a glutamatergic stimulation by submicromolar NMDA concentrations. We conclude that in vivo the NMDA‐evoked striatal glutamate release is mediated by activation of striatofugal GABAergic neurons and requires activation of striatal NK1 and dopamine receptors. Endogenous striatal dopamine inhibits or potentiates the NMDA action depending on the strength of the excitatory stimulus (i.e. the NMDA concentration).
Peptide YY administration into the posterior hypothalamic nucleus of the rat evokes cardiovascular changes by non‐adrenergic, non‐cholinergic mechanisms
Authors: Martin J. R.
Published: March 2005

1 Microinjection of peptide YY (PYY) (0.23–2.3 nmol) into the posterior hypothalamic nucleus (PHN) of conscious rats evokes a dose‐dependent pressor response and a bradycardia.

2 The increase in mean arterial pressure evoked by 2.3 nmol of PYY was not blocked by intravenous pretreatment with: (i) the nicotinic ganglionic receptor antagonist pentolinium (PENT, 10 mg kg−1) alone, or in combination with the muscarinic receptor antagonist methylatropine (MeATR, 1 mg kg−1); (ii) the α1‐adrenoceptor antagonist prazosin (PRAZ, 0.2 mg kg−1); (iii) the V1‐vasopressin receptor antagonist [d(CH2)5Tyr(Me)]AVP (AVPX, 20 μg kg−1); (iv) the combination of AVPX, PENT and MeATR; (v) the combination of PRAZ, AVPX, PENT, MeATR, and the α2‐adrenoceptor antagonist yohimbine (0.3 mg kg−1); or (vi) the angiotensin II type 1 receptor antagonist ZD 7155 (1 mg kg−1).

3 Adrenal demedullation inhibited the PYY‐evoked responses of drug‐naïve rats, and rats pretreated with the combination of PENT, MeATR and AVPX.

4 Transection of the splanchnic nerve innervating the adrenal medullae attenuated the bradycardia, as did ZD 7155, but not the PYY‐evoked pressor response.

5 Systemic pretreatment of rats with the neuropeptide Y1 receptor antagonist BIBP 3226 (1 mg kg−1) blocked the PYY‐evoked cardiovascular changes, but not those evoked by microinjection of carbachol (5.5 nmol) into the PHN.

6 These results suggest that the cardiovascular changes evoked from the PHN by PYY requires the presence of the adrenal medullae, which are stimulated by: (i) a hormone to release an NPY‐like substance that evokes the pressor response, and (ii) the splanchnic nerve to evoke the release of a substance that results in the bradycardia.
HOUSEWORK VS. MARKETWORK: SOME EVIDENCE HOW THE DECISION IS MADE
Authors: Ferber Marianne A. , Greene Carole A.
Published: March 2005

Empirical research using the opportunity cost approach to estimating the value of non‐market work of women tends to focus on the value of actual or potential output produced at home and expected or actual earnings, and assume that a rational decision involves choosing the higher one. Evidence derived from data on young married women suggests that full‐time homemakers frequently are unable to provide estimates either of their potential earnings or of the lowest wage they would accept to enter the labor market, and that such estimates as they do provide are not soundly based. We also found that using wages of women in the labor market to estimate the value of the home time of full‐time homemakers involves upward bias. We conclude that there are good reasons for caution in using the opportunity cost approach.
Impact of an early pregnancy problem service on patient care and Emergency Department presentations
Authors: BROWNLEA Sandra , HOLDGATE Anna , THOU Stephen T. P. , DAVIS Gregory K.
Published: March 2005

Aim:  To examine the impact of a ‘next day’ outpatient clinic, the Early Pregnancy Problem Service, on patients presenting to the Emergency Department with pain or bleeding in the first trimester of pregnancy. This clinic was established in June 1996.

Methods:  This was a retrospective study involving patients presenting to the Emergency Department with pain or bleeding in early pregnancy. Data was collected from the Emergency Department Information System and the medical records and then compared over the same 2‐month periods in different years. These were in, 1996 (preclinic), 1997, 2000 and 2003. The primary outcome was length of stay in the Emergency Department for women with first trimester pain or bleeding that did not require hospital admission. Secondary outcomes were the proportion of such patients presenting and re‐presenting to the Emergency Department.

Results:  Following establishment of the clinic there was a significant reduction in the median length of stay in the Emergency Department for patients who were discharged (136 mins in 1996 vs 107 mins in 2003; P < 0.001). There were non‐significant reductions in the proportion of patients presenting to the Emergency Department (1.5% in 1996 vs 1.1% in 2003; P = 0.09) and the number re‐presenting (16% in 1996 vs 7% in 2003; P = 0.15).

Conclusion:  Following the introduction of the Early Pregnancy Problem Service, women presenting with first trimester pain or bleeding who did not require emergency hospital admission spent significantly less time in the Emergency Department.
A randomised trial of surgical, medical and expectant management of first trimester spontaneous miscarriage
Authors: SHELLEY Julia M. , HEALY David , GROVER Sonia
Published: March 2005

Background:  Medical management and expectant care have been considered possible alternatives to surgical evacuation of the uterus for first trimester spontaneous miscarriage in recent years.

Aim:  To compare the effectiveness and safety of medical and expectant management with surgical management for first trimester incomplete or inevitable miscarriage.

Methods:  Forty women were recruited following diagnosis of incomplete or inevitable miscarriage, and randomised to surgical, medical or expectant care via an off‐site, computerised enrolment system. The primary outcome was the effectiveness of medical (vaginal misoprostol) and expectant management relative to surgical evacuation, assessed at 10–14 days and 8 weeks post‐recruitment. Infection, pain, bleeding, anxiety, depression, physical and emotional recovery were assessed also. Analysis was by intention‐to‐treat.

Results:  Effectiveness at 8 weeks was lower for medical (80.0%) and expectant (78.6%) than for surgical management (100.0%). Two women in the medical group had confirmed infections. Bleeding lasted longer in the expectant group than in the surgical group. There were no significant differences in pain, physical recovery, anxiety or depression between the groups. 54.6%, 42.9% and 57.1% of the surgical, medical and expectant groups respectively would opt for the same treatment again.

Conclusion:  Expectant care appears to be sufficiently safe and effective to be offered as an option for women. Medical management might carry a higher risk of infection than surgical or expectant care.
Efficacy of hyoscine‐N‐butyl bromide (Buscopan) suppositories as a cervical spasmolytic agent in labour
Authors: SIROHIWAL Daya , DAHIYA Krishna , DE Mandira
Published: March 2005

Objective:  To evaluate the efficacy and safety of hyoscine‐N‐butyl bromide (Buscopan) suppositories in the active phase of labour, i.e. once the labour is established.

Methods:  A non‐randomised controlled prospective study was carried out on 200 women in labour. In the active phase of labour, at 3 cm or more cervical dilatation, 100 women were administered Buscopan via suppository and 100 women (control) were not given any drug.

Results:  The duration of first stage of labour was 123.86 ± 68.89 (mean+‐standard deviation) minutes in the study group and 368.05 ± 133.0 min in the control group. These differences were statistically significant. There were no differences in the duration of the second and third stages of labour. There was no increased incidence of operative deliveries in the study group. No adverse effects were noted on the mother or fetus.

Conclusion:  Hyoscine‐N‐butyl bromide (HBB, Buscopan) suppositories were highly effective in shortening the duration of the first stage of labour.
Comparison of pulse methotrexate and pulse dactinomycin in the treatment of low‐risk gestational trophoblastic neoplasia
Authors: GILANI Mitra Modares , YARANDI Fariba , EFTEKHAR Zahra , HANJANI Parviz
Published: March 2005

Methotrexate and dactinomycin are efficient drugs in the treatment of patients with low‐risk gestational trophoblastic neoplasia (LRGTN). To compare the effectiveness of these two drugs in LRGTN, 46 patients were randomised to receive weekly intramuscular methotrexate at 30 mg/m2 (n = 28) or intravenous dactinomycin at 1.25 mg/m2 every 2 weeks (n = 18). Fourteen patients (50%) in the methotrexate group and 16 patients (89%) in the dactinomycin group achieved complete response. Greater patient convenience and a lower number of required visits make dactinomycin superior to other alternatives.
Demographic characteristics and clinical course in infants with moderate or severe neonatal encephalopathy
Authors: WEST Claire R. , HARDING Jane E. , KNIGHT David B. , BATTIN Malcolm R.
Published: March 2005

A chart review of 64 infants with moderate or severe neonatal encephalopathy showed that resuscitation was required for 61 (95%), respiratory support for 53 (83%) and anticonvulsants for 58 (91%). Death occurred in 2 (4%) infants with moderate encephalopathy and 12 (86%) with severe encephalopathy. In addition, subsequent neurodevelopment was abnormal in approximately a quarter of infants who survived after a moderate to severe encephalopathy.
Postoperative analgesic requirements – total laparoscopic hysterectomy versus vaginal hysterectomy
Authors: NASCIMENTO Marcelo Carraro , KELLEY Andrea , MARTITSCH Caroline , WEIDNER Ines , OBERMAIR Andreas
Published: March 2005

Background:  There is limited information available on the requirement for postoperative analgesic drugs in patients submitted to total laparoscopic hysterectomy (TLH) compared with patients undergoing vaginal hysterectomy (VH).

Aim:  To compare the postoperative analgesic requirements in patients who underwent a TLH with patients who had a VH.

Methods:  Chart review of 53 patients who had TLH and 47 who had VH and were seen postoperatively by an acute pain management service in order to assess postoperative analgesic requirements. Patient controlled analgesia (PCA) was part of the standard protocol for postoperative pain management. Analgesic requirement was recorded as the mean doses of morphine and number of days that patients used non‐steroidal anti‐inflammatory drugs (NSAIDs), oxycodone and tramadol.

Results:  The requirement for total morphine was approximately half the dose in patients who had a TLH (10.8 ± 12.6 mg) compared with patients who had a VH (19.4 ± 21.9 mg) (P 0.017). The length of use of NSAIDs was significantly reduced in patients who had undergone a TLH (2.0 ± 0.95 days) as compared with patients who had a VH (2.85 ± 1.1 days) (P < 0.0001).

Conclusions:  Patients submitted to TLH require less postoperative analgesic drugs when compared with patients who had VH. Prospective randomised trials are warranted to compare analgesic requirements between patients submitted to TLH and VH.