bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preoperative serum inhibin levels in patients with ovarian tumors
Authors: El‐Shalakany Amr , Abou‐Talib Yasser , Shalaby Hatem Saad , Sallam Maha 
Published: March 2004

AbstractAim:  To assess the value of preoperative determination of serum inhibin levels in the prediction of malignancy in women with ovarian tumors. The prediction of malignancy not only helps patient counseling regarding prognosis and extent of surgery but also allows for proper specialist referral.Methods:  Fifty women with clinically diagnosed ovarian tumors before surgery (patients group) and 32 healthy non‐pregnant women in the early follicular phase of their cycle (controls) were studied. Serum inhibin (total) levels and CA125 were determined using immunoenzymometric assay and enzyme immunoassay, respectively.Results:  In the patients group, 31 women had malignant ovarian tumors and 19 had benign tumors. Mean (SEM) serum inhibin levels were 0.94 (0.13) U/mL in the control group, 0.91 (0.7) U/mL in women with benign tumors and 1.9 (0.12) U/mL in women with malignant tumors; the differences are statistically significant (P < 0.01). Inhibin levels were significantly higher in women with late‐stage malignant ovarian tumors (III and IV) than in early stages (I and II) and showed no significant difference in relation to menopausal status or the presence of ascites. Taking the 95th centile inhibin level in the control group (1.155 U/mL) as a discriminator level, all women with benign tumors were negative while 67.7% of women with malignant tumors were positive. The inhibin level testing predicted malignancy with a sensitivity of 67.7%, 100% specificity, 100% positive predictive value and 65.52% negative predictive value. Combining CA125 levels (>35 U/mL) with serum inhibin levels (> 1.155 U/mL) improves sensitivity of predicting malignancy to 83.87% and negative predictive value to 75% while maintaining a specificity of 100% and a positive predictive value of 100%. Combining serum inhibin with sonography achieves 96.77% sensitivity and 73.68% specificity for detecting malignancy.Conclusion:  Preoperative serum inhibin levels in women with ovarian tumors are useful in the prediction of malignancy especially when combined with sonography.
Finite element analysis of notched bar skeletal point stresses and dimension changes due to creep
Authors: WEBSTER G. A. , NIKBIN K. M. , BIGLARI F. 
Published: March 2004

ABSTRACTIn this investigation, finite element calculations have been performed to obtain the creep stress distributions generated in circumferentially notched bar test‐pieces. They have also been made to determine the relation between axial extension and notch throat diameter changes. It has been found that an approximate skeletal point can be identified where the stress state is insensitive to the power law stress dependence of creep. Consistent trends in skeletal point stress ratios to those given in an existing Code of Practice for notch bar creep testing have been obtained. Nevertheless updated values, particularly for sharp notches, are proposed and these have now been inserted into a new version of the Code of Practice. In contrast, the link between extension and notch throat diameter changes has been found to depend on the creep stress index as well as the notch geometry. It is anticipated that the analysis can be used to establish the multi‐axial creep stress deformation and rupture behaviour of materials.
The multiaxial creep ductility of austenitic stainless steels
Authors: SPINDLER M. W. 
Published: March 2004

ABSTRACTCalculations of creep damage under conditions of strain control are often carried out using either a time fraction approach or a ductility exhaustion approach. In practice, calculations of creep damage are further complicated by the presence of multiaxial states of stress. In the case of the time fraction approach, there are a number of models that can be used to predict the effect of state of stress on creep rupture strength. In particular, Huddleston developed a model from data on stainless steels. The R5 procedure uses a ductility exhaustion approach to calculate creep damage and includes a model for use under triaxial states of stress. The aim of this paper is to describe the development of this model, which is based on considerations of cavity nucleation and growth and was developed from multiaxial creep data on Type 304 and 316 steels.
Fatigue‐creep and plastic collapse of notched bars
Authors: PONTER A. R. S. , CHEN H. , WILLIS M. R. , EVANS W. J. 
Published: March 2004

ABSTRACTThe paper describes a study of the application of a new assessment method, based on the linear matching method (LMM), to the creep fatigue of notched bars of Udimet 720Li at 650 °C. This high strength nickel based alloy is taken as typical of alloys used in high temperature gas turbine applications. The primary purpose of the study is to see whether it is possible to predict the failure modes for such alloys in terms of standard materials data by the evaluation of a sequence of simplified calculations corresponding to the steady state cyclic stress history. These calculations involve the evaluation of limit load, shakedown limit and ratchet limit for perfect plasticity, rapid cycle creep solutions and the evaluation of an elastic follow‐up factor. Within the limitations of the tests, the correlation between predicted failure mode and observed mode is very good and the calculations clearly show up the differences between the two types of notched bars discussed. This implies that LM methods are well suited to the evaluation of failure modes in materials of this type.
Modelling of damage development and failure in notched‐bar multiaxial creep tests
Authors: YATOMI M. , BETTINSON A. D. , O'DOWD N. P. , NIKBIN K. M. 
Published: March 2004

ABSTRACTFinite‐element predictions of creep rupture in notched specimens are presented in this work. A damage model linked to the creep strain rate and stress triaxiality has been used to predict creep life under multiaxial stress conditions and the predictions have been compared with experimental data for a C–Mn steel. Finite‐element analyses have been conducted using primary–secondary (PS) and primary–secondary–tertiary (PST) creep laws. As expected a PST analysis gives a shorter predicted rupture life than a PS analysis. An additional term was included in the model to allow for an increase in hydrostatic strain due to creep damage. The incorporation of this term improved the agreement between the experimental data and the finite‐element predictions. A further enhancement to the model was to model the initiation and growth of a sharp crack in the vicinity of the notch, through the use of a nodal release technique linked to the damage evolution. It was found that the predictions obtained using the nodal release technique were very similar to those from the PST creep model incorporating the hydrostatic damage term. The effect of mesh size has also been examined and the finite‐element predictions were seen to be quite mesh sensitive with a finer mesh generally giving a shorter predicted life.
Functional and morphological alterations in compound transgenic mice overexpreszing Cu/Zn superoxide dismutaze and amyloid precursor protein
Authors: Harris‐Cerruti Catherine , Kamsler Ariel , Kaplan Batia , Lamb Bruce , Segal Menahem , Groner Yoram 
Published: March 2004

AbstractDown's syndrome (DS), the phenotypic manifestation of trisomy 21, involves overexpression of chromosome 21‐encoded genes. The gene for amyloid precursor protein (APP), known to be involved in AD pathology, resides on chromosome 21 along with the gene for Cu/Zn superoxide dismutase (SOD1), a key enzyme in the metabolism of oxygen free radicals. We investigated the consequences of a combined increase in APP and SOD1, in a double‐transgenic (tg)‐APP–SOD1 mouse. These mice expressed severe impairment in learning, working and long‐term memory. Expression of long‐term potentiation in hippocampal slices was impaired in both tg‐SOD and tg‐APP–SOD mice, but not in tg‐APP mice, indicating that increased APP by itself did not affect in vitro synaptic plasticity. In tg‐APP–SOD mice, membrane‐bound high molecular weight APP species accumulated while APP cleavage products did not increase and levels of secreted APP were unchanged. Severe morphological damage, including lipofuscin accumulation and mitochondria abnormalities, were found in aged tg‐APP–SOD but not in the other mice. Thus, a combined elevation of the two chromosome 21 genes in tg‐APP–SOD mice induced age‐dependent alterations in morphological and behavioural functions.
Temporally induced Nurr1 can induce a non‐neuronal dopaminergic cell type in embryonic stem cell differentiation
Authors: Sonntag Kai‐Christian , Simantov Rabi , Kim Kwang‐Soo , Isacson Ole 
Published: March 2004

AbstractThe nuclear transcription factor Nurr1 is involved in the development and maintenance of the midbrain dopaminergic (DA) neuronal phenotype. We analysed the cellular and biological effects of Nurr1 during embryonic stem (ES) cell differentiation using the ROSA26‐engineered Tet‐inducible ES cell line J1‐rtTA that does not express transgenes in mature neurons. Induction of Nurr1 at nestin‐positive precursor and later stages of ES cell differentiation produced a non‐neuronal DA cell type including functional DA transporters. In these cells, we found a clear correlation between Nurr1 and TH gene expression and specific midbrain DA cellular markers such as AADC, AHD2 and calbindin. Nurr1 did not alter gene expression of non‐DA neuronal phenotypes and did not influence other midbrain developmental transcription factors, such as Otx1, Otx2, En‐1, GBX2, Pitx3 and lmx1b. In addition, Nurr1 expression was required for maintenance of the DA phenotype and mediated up‐regulation of the tyrosine kinase Ret and associated trophic factor GDNF‐family receptors α 1, 2, and 4. This demonstrates that Nurr1 is sufficient to induce and maintain a midbrain‐like DA biochemical and functional cellular phenotype independent of neurogenesis.
Low‐dose γ‐irradiation promotes survival of injured neurons in the central nervous system via homeostasis‐driven proliferation of T cells
Authors: Kipnis Jonathan , Avidan Hila , Markovich Yifat , Mizrahi Tal , Hauben Ehud , Prigozhina Tatyana B. , Slavin Shimon ,   Michal Schwartz
Published: March 2004

AbstractProtective autoimmunity was only recently recognized as a mechanism for attenuating the progression of neurodegeneration. Using a rat model of optic nerve crush or contusive spinal cord injury, and a mouse model of neurodegenerative conditions caused by injection of a toxic dose of intraocular glutamate, we show that a single low dose of whole‐body or lymphoid‐organ γ‐irradiation significantly improved the spontaneous recovery. Animals with severe immune deficiency or deprived of mature T cells were unable to benefit from this treatment, suggesting that the irradiation‐induced neuroprotection is immune mediated. This suggestion received further support from the findings that irradiation was accompanied by an increased incidence of activated T cells in the lymphoid organs and peripheral blood and an increase in mRNA encoding for the pro‐inflammatory cytokines interleukin‐12 and interferon‐γ, and that after irradiation, passive transfer of a subpopulation of suppressive T cells (naturally occurring regulatory CD4+CD25+ T cells) wiped out the irradiation‐induced protection. These results suggest that homeostasis‐driven proliferation of T cells, induced by a single low‐dose irradiation, leads to boosting of T cell‐mediated neuroprotection and can be utilized clinically to fight off neurodegeneration and the threat of other diseases in which defense against toxic self‐compounds is needed.
Neuromodulation of the locomotor network by dopamine in the isolated spinal cord of newborn rat
Authors: Barrière Grégory , Mellen Nicholas , Cazalets Jean‐René 
Published: March 2004

AbstractWe have analysed the action of the neuromodulatory catecholamine, dopamine (DA), on the lumbar locomotor network using an isolated in vitro newborn rat spinal cord preparation. We have also attempted to determine the respective contribution of the D1‐ and D2‐like receptors on the dopamine‐mediated effects. Bath application of DA‐induced slow locomotor‐like rhythmic activity (cycle‐period 20–30 s) in ventral motor roots. Bursts were alternating between segmental right and left side and between ipsilateral flexor and extensor units. This rhythm was blocked by D1 (SCH‐23390) and D2 (raclopride, sulpiride) receptor antagonists, but was unaffected by the dopamine‐β‐hydroxylase blocker, fusaric acid, thereby ruling out indirect noradrenaline‐mediated effects. The D1 agonist, SKF‐81297 induced prolonged slow rhythmic bursting, while the selective D2 agonists, quinpirole and quinelorane, had no effect. DA and the D1 agonist, SKF‐81297 also increased the period and burst amplitude of N‐methyl‐d‐l‐aspartate‐induced locomotor activity. The effects of dopamine and SKF‐81297 on the N‐methyl‐d‐l‐aspartate‐induced rhythm were long‐lasting; persisting for 1 hour after washout. The DA action was blocked by MDL‐12 330 A, an inhibitor of adenylate cyclase, suggesting the involvement of cAMP. Together these results indicate that dopamine can exert neuromodulatory actions on mammalian motor networks via short‐lasting permissive influences and a newly reported, long‐lasting modulation of motor network activity.
Learning and memory performance in mice lacking the GAL‐R1 subtype of galanin receptor
Authors: Wrenn Craige C. , Kinney Jefferson W. , Marriott Lisa K. , Holmes Andrew , Harris Ashley P. , Saavedra Maria C. , Starosta Grzegorz , Innerfield Caitlin E. , Jacoby Arie S. , Shine John , Iismaa Tiina P. , Wenk Gary L. , Crawley Jacqueline N. 
Published: March 2004

AbstractThe neuropeptide galanin induces performance deficits in a wide range of cognitive tasks in rodents. Three G‐protein‐coupled galanin receptor subtypes, designated GAL‐R1, GAL‐R2 and GAL‐R3, have been cloned. The present study examined the role of GAL‐R1 in cognition by testing mice with a null mutation in Galr1 on several different types of learning and memory tasks. Assessments of general health, neurological reflexes, sensory abilities and motor functions were conducted as control measures. Mutant mice were unimpaired in social transmission of food preference and the Morris water maze. In tests of fear conditioning, mutant mice were unimpaired in a delay version of cued fear conditioning. However, mice homozygous for the null mutation were impaired in a trace version of cued fear conditioning. Mutant mice were unimpaired in contextual fear conditioning, whether training was by the delay or trace protocol. General health, neurological reflexes, sensory abilities and motor functions did not differ across genotypes, indicating that the trace fear conditioning deficit was not an artifact of procedural disabilities. The findings of normal performance on several cognitive tasks and a selective deficit in trace cued fear conditioning in homozygous GAL‐R1 mutant mice are discussed in terms of hypothesized roles of the GAL‐R1 subtype. The generally normal phenotype of GAL‐R1 null mutants supports the use of this line for identification of the receptor subtypes that mediate the cognitive deficits produced by exogenous galanin.
Hippocampal neurons in organotypic slice culture are highly resistant to damage by endogenous and exogenous nitric oxide
Authors: Keynes Robert G. , Duport Sophie , Garthwaite John 
Published: March 2004

AbstractNitric oxide (NO) has been proposed to mediate neurodegeneration arising from NMDA receptor activity, but the issue remains controversial. The hypothesis was re‐examined using organotypic slice cultures of rat hippocampus, with steps being taken to avoid known artefacts. The NO‐cGMP signalling pathway was well preserved in such cultures. Brief exposure to NMDA resulted in a concentration‐dependent delayed neuronal death that could be nullified by administration of the NMDA antagonist MK801 (10 µm) given postexposure. Two inhibitors of NO synthesis failed to protect the slices, despite fully blocking NMDA‐induced cGMP accumulation. By comparing NMDA‐induced cGMP accumulation with that produced by an NO donor, toxic NMDA concentrations were estimated to produce only physiological NO concentrations (2 nm). In studies of the vulnerability of the slices to exogenous NO, it was found that continuous exposure to up to 4.5 µm NO failed to affect ATP levels (measured after 6 h) or cause damage during 24 h, whereas treatment with the respiratory inhibitors myxothiazol or cyanide caused ATP depletion and complete cell death within 24 h. An NO concentration of 10 µm was required for ATP depletion and cell death, presumably through respiratory inhibition. It is concluded that sustained activity of neuronal NO synthase in intact hippocampal tissue can generate only low nanomolar NO concentrations, which are unlikely to be toxic. At the same time, the tissue is remarkably resistant to exogenous NO at up to 1000‐fold higher concentrations. Together, the results seriously question the proposed role of NO in NMDA receptor‐mediated excitotoxicity.
Asymmetric activation to the context‐dependent right in the right inferior frontal region
Authors: Misaki Masaya , Matsumoto Eriko , Miyauchi Satoru 
Published: March 2004

AbstractIn human spatial recognition, right and left are not recognized symmetrically. Although there have been many studies on the hemispheric asymmetry of the human brain, asymmetries in high‐level recognition (such as independence from input or output hemisphere) have not been studied extensively. We found that the human brain recognizes right and left asymmetrically in high‐level recognition. Experiments were performed in which participants crossed their hands and were required to judge the side of a tactile stimulus on the index finger in two different contexts: ‘which hand was touched’ or ‘on which side of the space the touched hand was located’. The right inferior frontal region was significantly more activated by the ‘contextually defined right’ stimulus (right‐hand stimulation in the ‘which hand’ context and right‐space stimulation in the ‘which space’ context) than by the ‘contextually defined left’ stimulus. However, no activation that was more activated by the ‘contextually defined left’ than by the ‘contextually defined right’ was found. This asymmetric activation suggests that ‘right’ is the more outstanding side for human spatial recognition.
Pharmacological profile of nociceptin/orphanin FQ receptors regulating 5‐hydroxytryptamine release in the mouse neocortex
Authors: Mela Flora , Marti Matteo , Ulazzi Linda , Vaccari Elvis , Zucchini Silvia , Trapella Claudio , Salvadori Severo , Beani Lorenzo , Bianchi Clementina , Morari Michele 
Published: March 2004

AbstractA synaptosomal preparation was employed to pharmacologically characterize the role of presynaptic nociceptin/orphanin FQ (N/OFQ) receptors (NOP receptors) in the regulation of 5‐hydroxytryptamine release in the Swiss mouse neocortex. In the present study, the NOP receptor ligands N/OFQ, Ac‐RYYRWK‐NH2 and [Phe1ψ(CH2‐NH)Gly2]N/OFQ(1–13)‐NH2 inhibited the K+‐induced [3H]‐5‐HT overflow with similar maximal effects (≈−35%) but different potencies (pEC50 of 8.56, 8.35 and 7.23, respectively). The novel agonist [Arg14,Lys15]N/OFQ also inhibited [3H]‐5‐HT overflow, but the concentration–response curve was biphasic and the efficacy higher (≈−45%). Receptor selectivity of NOP receptor agonists was demonstrated by showing that synaptosomes from NOP receptor knockout mice were unresponsive to N/OFQ, [Arg14,Lys15]N/OFQ and [Phe1ψ(CH2‐NH)Gly2]N/OFQ(1–13)‐NH2 but maintained full responsiveness to endomorphin‐1. Moreover, the inhibitory effect of N/OFQ was prevented by peptide ([Nphe1]N/OFQ(1–13)‐NH2 and UFP‐101) and nonpeptide (J‐113397 and JTC‐801) NOP receptor selective antagonists. Desensitization occurred under perfusion with high (3 and 10 µm) N/OFQ concentrations. This phenomenon was prevented by the protein kinase C inhibitor, bisindolylmaleimide. Moreover, N/OFQ‐induced desensitization did not affect mu opioid receptor responsiveness. Finally, it was observed in a similar preparation of rat cerebrocortical synaptosomes, although it was induced by higher N/OFQ concentrations than that used in the mouse. Together, these findings indicate that presynaptic NOP receptors inhibit 5‐hydroxytryptamine release in the mouse neocortex. Based on present and previous studies, we conclude that NOP receptors in the mouse are subtly different from the homologous receptor population in the rat, strengthening the view that there exist species differences in the pharmacology of central NOP receptors.
Daily body temperature rhythm and heat tolerance in TRPV1 knockout and capsaicin pretreated mice
Authors: Szelényi Z. , Hummel Z. , Szolcsányi J. , Davis J. B. 
Published: March 2004

AbstractDaily body temperature (DBT) rhythm of mice lacking one of the transient receptor potential (TRP) family of proteins, the capsaicin receptor or TRPV1, was recorded by biotelemetry and found to have significantly higher amplitude than that of wild‐type mice. Capsaicin‐desensitized wild‐mice exhibited an even higher DBT amplitude than did TRPV1 deficient mice. A standard heat load (radiant temperature of 36–37 °C) resulted in similar rises in body core temperature in wild‐type mice and in TRPV1 deficient mice, while capsaicin‐desensitized wild‐type mice exhibited a robust heat‐intolerance. The lack of TRPV1 slightly modifies amplitude of daily body temperature rhythm but does not seem to influence physiological heat defence in mice. In vivo evidence for a TRP protein functioning in the physiological heat‐defence range is still lacking.
Regulation of MAPK/ERK phosphorylation via ionotropic glutamate receptors in cultured rat striatal neurons
Authors: Mao Limin , Tang Qingsong , Samdani Shazia , Liu Zhenguo , Wang John Q. 
Published: March 2004

AbstractExtracellular signals may regulate mitogen‐activated protein kinase (MAPK) cascades through a receptor‐mediated mechanism. As a signaling superhighway to the nucleus, active Ras‐MAPK cascades phosphorylate transcription factors and facilitate gene expression. In cultured rat striatal neurons, the present work systemically examined the linkage between glutamate receptors and the extracellular signal‐regulated kinase 1/2 (ERK1/2) subclass of MAPK. We found that glutamate induced a rapid and transient phosphorylation of ERK1/2. Similar responses of ERK1/2 phosphorylation were also induced by the ligands selective for each of three subtypes of ionotropic receptors (NMDA, AMPA and kainate), although not by the subgroup‐selective agonists for three subgroups of metabotropic glutamate receptors after 8–9 days in culture. The ERK1/2 phosphorylation induced by all ionotropic receptor agents was dose‐, time‐ and Ca2+ influx‐dependent and occurred in neurons, but not glia. The NMDA‐, AMPA‐ and kainate‐induced ERK1/2 phosphorylation was blocked only by the antagonists selective for respective subtypes. The ERK1/2 phosphorylation induced by these agents was also sensitive to the MAPK kinase 1 (MEK1) inhibitor PD98059 and the MEK1/2 inhibitor U0126. In a further attempt to evaluate the role of active ERK1/2 in activating a downstream transcription factor cAMP response element‐binding protein (CREB), NMDA, AMPA, and kainate were found to increase CREB phosphorylation. The NMDA‐ and AMPA/kainate‐induced CREB phosphorylation was completely and partially blocked by U0126, respectively. These results revealed a positive linkage between ionotropic glutamate receptors and MEK‐sensitive ERK1/2 phosphorylation in striatal neurons. The active ERK1/2 cascade activates the downstream transcription factor CREB to participate in the regulation of gene expression.