bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bayesian Classification of Tumours by Using Gene Expression Data
Authors: Mallick Bani K. , Ghosh Debashis , Ghosh Malay 
Published: March 2005

SummaryPrecise 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.
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

AbstractStudies 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

AbstractWe 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

AbstractObstructive 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

Abstractβ‐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

AbstractThe 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

AbstractMacromolecules 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

AbstractNeurotrophins 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

AbstractThe 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

Summary 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.
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

AbstractAim:  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

AbstractBackground:  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

AbstractObjective:  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

AbstractMethotrexate 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

AbstractA 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.