bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thaliporphine protects ischemic and ischemic‐reperfused rat hearts via an NO‐dependent mechanism
Authors: Hung Li‐Man , Lee Shoei‐Sheng , Chen Jan‐Kan , Huang Shiang‐Suo , Su Ming‐Jai 
Published: August 2002

AbstractIn ischemia or ischemia‐reperfusion (I/R), nitric oxide (NO) can potentially exert several beneficial effects. Thaliporphine, a natural alkaloid with Ca2+ channel‐activating and Na+/K+ channel‐blocking activities, increased NO levels and exerted cardioprotective action in ischemic or I/R rats. The role of NO in the cardioprotective actions of thaliporphine was assessed. The severity of rhythm disturbances and mortality in anesthetized rats with either coronary artery occlusion for 30 min, or 5 min followed by 30‐min reperfusion, were monitored and compared in thaliporphine‐ vs. placebo‐treated groups. Thaliporphine treatment significantly increased NO and decreased lactate dehydrogenase (LDH) levels in the blood during the end period of ischemia or I/R. These changes in NO and LDH levels by thaliporphine were associated with a reduction in the incidence and duration of ventricular tachycardia (VT) and ventricular fibrillation (VF) during ischemic or I/R period. The mortality of animals was also completely prevented by 1 × 10–8 moles/kg of thaliporphine. In animals subjected to 4 h of left coronary artery occlusion, 1 × 10–7 moles/kg of thaliporphine dramatic reduced cardiac infarct zone from 46 ± 6% to 7.1 ± 1.9%. Inhibition of NO synthesis with 3.7 × 10–6 moles/kg of Nω ‐nitro‐L‐arginine methyl ester (L‐NAME) abolished the beneficial effects of thaliporphine during 30 min or 4 h myocardial ischemia. However, the antiarrhythmic activity and mortality reduction efficacy of thaliporphine during reperfusion after 5 min of ischemia was only partially antagonized by L‐NAME. These results showed that thaliporphine efficiently exerted the cardioprotections either in acute or prolonged coronary artery occlusion or occlusion‐reperfusion situations. The fact that thaliporphine induced cardioprotective effects were abrogated by L‐NAME indicates that NO is an important mediator for the cardioprotective effects of thaliporphine in acute or prolonged ischemia, whereas antioxidant activities may contribute to the protection of I/R injury. Drug Dev. Res. 52:446–453, 2001. © 2001 Wiley‐Liss, Inc.
Lipophilic methotrexate conjugates with glucose‐lipoamino acid moieties: Synthesis and in vitro antitumor activity
Authors: Pignatello Rosario , Vicari Luisa , Sorrenti Valeria , Di Giacomo Claudia , Spampinato Giuseppina , Puglisi Giovanni , Toth Istvan 
Published: August 2002

AbstractTo obtain methotrexate (MTX) derivatives with a balanced hydrolipophilic character, we synthesized a series of conjugates in which the drug was linked to lipoamino acid (LAA)‐glucose residues (LAAG‐MTX). These conjugates displayed increased solubility in polar media compared with the corresponding LAA‐MTX conjugates previously described. In vitro biological testing of LAAG‐MTX indicated that the introduction of the sugar moiety decreased the biological activity of these MTX conjugates. The tetradecyl derivative 6b, however, was effective in inhibiting the dihydrofolate reductase activity in vitro and showed an inhibitory effect on human lymphoblastoid cell growth. Drug Dev. Res. 52:454–461, 2001. © 2001 Wiley‐Liss, Inc.
Cardiac effects of diinosine tetraphosphate, a putative dinucleotide receptor antagonist
Authors: Stavrou Brigitte M. , Abdel‐Rahman Saif‐El‐Dean Tawfik , Pintor Jesús , Gualix Javier , Miras‐Portugal M. Teresa , Sheridan Desmond J. , Flores Nicholas A. 
Published: August 2002

AbstractThe cardiac electrophysiological and vasomotor effects of diinosine tetraphosphate (Ip4I, 10 nM and 1 μM) were examined in guinea pig isolated hearts together with its ability to antagonize the effects of diadenosine tetraphosphate (Ap4A, 1 nM and 1 μM). Ip4I had no effects on action potential duration or refractory period and attenuated the electrophysiological effects of Ap4A at both concentrations. Although Ip4I increased coronary perfusion pressure, the vasomotor effects of Ap4A were resistant to antagonism by Ip4I. These observations support data from neural tissues and indicate that diinosine polyphosphates may antagonize cardiac electrophysiological effects of diadenosine polyphosphates. Drug Dev. Res. 52:500–503, 2001. © 2001 Wiley‐Liss, Inc.
Characterisation of the P2X7 receptor‐mediated signalling pathway associated with rapid killing of intracellular mycobacteria within human macrophages
Authors: Stober Carmel B. , Ben‐Smith Anne , Kumararatne Dinikantha , Lammas David A. 
Published: August 2002

AbstractInvestigation of the P2X7 receptor‐associated signalling events following ATP stimulation of Mycobacterium bovis BCG‐infected human macrophages revealed that ATP‐mediated cell death and associated mycobacterial killing could be functionally uncoupled. Inhibitors of phospholipase D (PLD) (wortmannin and butan‐1‐ol), phospholipase A2 (PLA2) (GW 624A and GW 625A) and the mitogen‐activated protein kinase (MAPK) pathway (SB203580 and PD98059) all antagonised the ATP‐mediated killing of intracellular mycobacteria, but had no effect on ATP‐induced macrophage death. Inhibitors of protein kinase C (PKC), protein tyrosine kinases (PTKs), and protein serine/threonine phosphatases (PSTPs) were ineffective against either ATP‐stimulated cell death or bacterial killing. The mycobactericidal effects of ATP were not associated with the induction of apoptosis per se as the broad spectrum caspase inhibitor, ZVAD‐fmk, failed to block killing of mycobacteria within human macrophages. Inhibitors of protein synthesis (cycloheximide) and transcription (actinomycin D) were also ineffective against the cytotoxic and bactericidal responses of ATP, suggesting that the terminal effector mediator(s) involved is preformed and does not require de novo synthesis. Immunoelectron microscopy studies using intracellular probes to identify lysosomes revealed that ATP treatment of BCG‐infected macrophages induced the progressive colocalisation of mycobacteria‐containing phagosomes with lysosomes. The data suggests that ATP‐induced killing of intracellular mycobacteria involves the cellular activation of PLD, PLA2, and MAP kinase, and these signalling events lead to the maturation of the BCG‐containing phagosome culminating in the demise of the invading mycobacteria. Drug Dev. Res. 53:105–116, 2001. © 2001 Wiley‐Liss, Inc.
P2 nucleotide receptors in osteoclasts
Authors: Naemsch Lin N. , Du Xiaobing , Sims Stephen M. , Dixon S. Jeffrey 
Published: August 2002

AbstractOsteoclasts are large, multinucleated cells responsible for the resorption of bone and other mineralized tissues. Whereas low concentrations of extracellular ATP stimulate osteoclast formation and resorptive activity, high concentrations inhibit osteoclast formation. Cell surface receptors for nucleotides are classified into two families—P2X (ligand‐gated channels nonselective for cations) and P2Y (G‐protein‐coupled receptors linked, in most cases, to release of Ca2+ from intracellular stores). Several subtypes of P2 receptors are expressed by mammalian osteoclasts. The P2X4 receptor has been identified at both protein and messenger RNA levels and ATP activates a nonselective cation current with properties similar to that mediated by the cloned P2X4 channel. The P2X2 receptor is also expressed; however, currents with properties of P2X2 have yet to be identified. Functional and expression studies also support the existence of the P2X7 receptor, which is activated by high concentrations of ATP. Application of nucleotides to osteoclasts elicits transient elevation of cytosolic free Ca2+ concentration and activation of Ca2+‐dependent K+ channels. Both these responses are mediated, at least in part, by release of Ca2+ from intracellular stores, consistent with the presence of functional P2Y receptors. Expression of P2Y1 and P2Y2 receptors has been demonstrated in mammalian osteoclasts. The presence of multiple subtypes of P2 receptors may account for the biphasic effects of extracellular nucleotides on osteoclast function. These receptors represent potential targets for the development of novel therapeutics to inhibit bone resorption in diseases such as rheumatoid arthritis, osteoporosis, tumor‐induced osteolysis, and periodontitis. Drug Dev. Res. 53:130–139, 2001. © 2001 Wiley‐Liss, Inc.
Independent signaling pathways in ATP‐evoked secretion of plasminogen and cytokines from microglia
Authors: Inoue Kazuhide 
Published: August 2002

AbstractWe investigated the action of ATP on the secretion of plasminogen, TNF‐α, and IL‐6 from microglia. ATP (10–100 μM) stimulated the release of plasminogen from rat cultured microglia in a concentration‐dependent manner with a peak response at 5–10 min after the stimulation. The release was dependent on extracellular Ca2+ and was blocked by pretreatment with oxidized ATP, a blocker of P2X7. UTP, an agonist of P2Y2, also stimulated the release of plasminogen from a subpopulation (about 20% of total cells) of cultured microglia. The release was also dependent on extracellular Ca2+, suggesting a role of stocker‐operated calcium entry (SOC). ATP potently stimulated TNF‐α release from 2 h after the stimulation with TNF‐α mRNA expression in primary cultures of rat brain microglia. The TNF‐α release was maximally elicited by 1 mM ATP and 2′‐ and 3′‐O‐(4‐benzoylbenzoyl)‐adenosine 5′‐triphosphate (BzATP), a P2X7 selective agonist, suggesting the involvement of P2X7. This TNF‐α release was correlated with a sustained Ca2+ influx. The release was inhibited by PD98059, an inhibitor of MEK1 which activates extracellular signal‐regulated protein kinase (ERK), and SB203580, an inhibitor of p38 MAP kinase. However, both ERK and p38 were rapidly activated by ATP even in the absence of extracellular Ca2+. These results indicate that extracellular ATP triggers TNF‐α release in rat microglia via P2X7 in a manner dependent on the sustained Ca2+ influx and via the ERK/p38 cascade independently of Ca2+ influx. ATP caused the mRNA expression and release of IL‐6 in a concentration‐dependent manner in MG‐5. The physiological meaning of these independent release mechanisms is also discussed. Drug Dev. Res. 53:166–171, 2001. © 2001 Wiley‐Liss, Inc.
Antinociceptive profile of the natural cholinesterase inhibitor huperzine A
Authors: Galeotti Nicoletta , Ghelardini Carla , Di Cesare Mannelli Lorenzo , Bartolini Alessandro 
Published: August 2002

AbstractThe antinociceptive effect of huperzine A, a novel cholinesterase inhibitor, was investigated in the mouse hot‐plate and abdominal constriction tests. Huperzine A induced a dose‐dependent antinociception (70–110 μg kg–1 i.p.) which was prevented by scopolamine (0.1 mg kg–1 i.p.) and S‐(–)‐ET 126 (0.01 μg per mouse i.c.v.), but not by naloxone (1 mg kg–1 i.p.), mecamylamine (2 mg kg–1 i.p.), α‐methyl‐p‐tyrosine (100 mg kg–1 i.p.), or CGP 35348 (100 mg kg–1 i.p.). A dose‐dependent inhibition of the antinociception induced by huperzine A (110 μg kg–1 i.p.) was observed after inactivation of the M1 gene by an antisense oligodeoxyribonucleotide (aODN). This effect was detected 24 h after the last intracerebroventricular injection of aODN. Time‐course experiments revealed that, after the end of the aODN treatment, sensitivity to analgesic drugs progressively appeared, reaching the normal range at 96 h. Huperzine A, at the maximal effective doses, did not produce any alteration of mice motor coordination, as revealed by rota‐rod experiments. These results indicate that huperzine A is endowed by muscarinic antinociceptive properties mediated by the activation of central M1 muscarinic receptor subtype. Drug Dev. Res. 54:19–26, 2001. © 2001 Wiley‐Liss, Inc.
Clinical application of NKT cell assays to the prediction of type 1 diabetes
Authors: Poulton Lynn D. , Baxter Alan G. 
Published: August 2002

AbstractType 1 diabetes is a disease characterised by disturbed glucose homeostasis, which results from autoimmune destruction of the insulin‐producing beta cells in the pancreas. The autoimmune attack, while not yet fully characterised, exhibits components of both mis‐targeting and failed tolerance induction. The involvement of non‐classical lymphocytes in the induction and maintenance of peripheral tolerance has recently been recognised and natural killer T (NKT) cells appear to play such a role. NKT cells are a subset of T cells that are distinct in being able to produce cytokines such as IL‐4 and IFN‐γ extremely rapidly following activation. These lymphocytes also express some surface receptors, and the lytic activity, characteristic of NK cells. Deficiencies in NKT cells have been identified in animal models of type 1 diabetes, and a causal association has been demonstrated by adoptive transfer experiments in diabetes‐prone NOD mice. Preliminary work suggests that a similar relationship may exist between deficiencies in NKT cells and type 1 diabetes in humans, although the techniques reported to date would be difficult to translate to clinical use. Here, we describe methods appropriate to the clinical assessment of NKT cells and discuss the steps required in the assessment and validation of NKT cell assays as a predictor of type 1 diabetes. Copyright © 2001 John Wiley & Sons, Ltd.
Docking protein SNT1 is a critical mediator of fibroblast growth factor signaling during Xenopus embryonic development
Authors: Akagi Keiko , Kyun Park Eui , Mood Kathleen , Daar Ira O. 
Published: August 2002

AbstractThe docking protein SNT1/FRS2 (fibroblast growth factor receptor substrate 2) is implicated in the transmission of extracellular signals from several growth factor receptors to the mitogen‐activated protein (MAP) kinase signaling cascade, but its biological function during development is not well characterized. Here, we show that the Xenopus homolog of mammalian SNT1/FRS‐2 (XSNT1) plays a critical role in the appropriate formation of mesoderm‐derived tissue during embryogenesis. XSNT1 has an expression pattern that is quite similar to the fibroblast growth factor receptor‐1 (FGFR1) during Xenopus development. Ectopic expression of XSNT1 markedly enhanced the embryonic defects induced by an activated FGF receptor, and increased the MAP kinase activity as well as the expression of a mesodermal marker in response to FGF receptor signaling. A loss‐of‐function study using antisense XSNT1 morpholino oligonucleotides (XSNT‐AS) shows severe malformation of trunk and posterior structures. Moreover, XSNT‐AS disrupts muscle and notochord formation, and inhibits FGFR‐induced MAP kinase activation. In ectodermal explants, XSNT‐AS blocks FGFR‐mediated induction of mesoderm and the accompanying elongation movements. Our results indicate that XSNT1 is a critical mediator of FGF signaling and is required for early Xenopus development. © 2002 Wiley‐Liss, Inc.
Induction of chondrogenesis in neural crest cells by mutant fibroblast growth factor receptors
Authors: Petiot Anita , Ferretti Patrizia , Copp Andrew J. , Chan Chi‐Tsung Joseph 
Published: August 2002

AbstractActivating mutations in human fibroblast growth factor receptors (FGFR) result in a range of skeletal disorders, including craniosynostosis. Because the cranial bones are largely neural crest derived, the possibility arises that increased FGF signalling may predispose to premature/excessive skeletogenic differentiation in neural crest cells. To test this hypothesis, we expressed wild‐type and mutant FGFRs in quail embryonic neural crest cells. Chondrogenesis was consistently induced when mutant FGFR1‐K656E or FGFR2‐C278F were electroporated in ovo into stage 8 quail premigratory neural crest, followed by in vitro culture without FGF2. Neural crest cells electroporated with wild‐type FGFR1 or FGFR2 cDNAs exhibited no chondrogenic differentiation in culture. Cartilage differentiation was accompanied by expression of Sox9, Col2a1, and osteopontin. This closely resembled the response of nonelectroporated neural crest cells to FGF2 in vitro: 10 ng/ml induces chondrogenesis, Sox9, Col2a1, and osteopontin expression, whereas 1 ng/ml FGF2 enhances cell survival and Sox9 and Col2a1 expression, but never induces chondrogenesis or osteopontin expression. Transfection of neural crest cells with mutant FGFRs in vitro, after their emergence from the neural tube, in contrast, produced chondrogenesis at a very low frequency. Hence, mutant FGFRs can induce cartilage differentiation when electroporated into premigratory neural crest cells but this effect is drastically reduced if transfection is carried out after the onset of neural crest migration. © 2002 Wiley‐Liss, Inc.
Perturbation of extracellular matrix prevents association of the otic primordium with the posterior rhombencephalon and inhibits subsequent invagination
Authors: Visconti Richard P. , Hilfer S. Robert 
Published: August 2002

AbstractIn the avian embryo, the otic primordia become visible by Hamburger and Hamilton stage 10 as a pair of thickened regions of head ectoderm. In contrast to other epithelial primordia, invagination occurs by means of formation of a series of folds in distinct areas of the primordium, giving the otic vesicle a box‐like appearance. Because previous work has shown that otic invagination is ATP and calcium independent, it is unlikely that cytoskeletal changes are the primary mechanism responsible for invagination as in other epithelial primordia. Interaction of the primordium with surrounding tissues may provide the force for otic invagination. These extracellular forces may be transduced through extracellular matrix macromolecules and their cell surface receptors. This investigation tests the hypothesis that fusion of the otic and hindbrain basal laminae between stages 11 and 13 is necessary for normal invagination. Perturbation of binding of the otic primordium to the neural tube was accomplished by means of microinjection of antibodies to various extracellular matrix components and integrin subunits into the head mesenchyme in the otic region at stage 10. Only antibodies to laminin and integrins caused detachment of the otic primordium from the hindbrain. These experiments suggest that fusion of the otic and hindbrain basal laminae is required for subsequent invagination and, furthermore, that this event is mediated by components of the extracellular matrix. © 2001 Wiley‐Liss, Inc.
Cross‐linguistic transfer of phonological skills: a Malaysian perspective
Authors: Gomez Caroline , Reason Rea 
Published: August 2002

AbstractThis study examined the phonological and reading performance in English of Malaysian children whose home language was Bahasa Malaysia (BM). A sample of 69 Malaysian Standard Two pupils (aged 7–8 years) was selected for the study. Since commencing school at the age of 6 years, the children had been learning to read in BM and had subsequently also been learning to read in English for some 12 months. The study was part of a larger scale research programme that fully recognized the limitations of tests that had not been developed and standardized in Malaysia. Nevertheless, as a first step to developing such tests, a comparison with existing norms for the Phonological Assessment Battery (PhAB) and the Wechsler Objective Reading Dimension (WORD) was undertaken in relation to information about the children's L1 and L2 language competencies. Results showed that the children's performance on PhAB was at least comparable to the UK norms while, not surprisingly, they fared less well on WORD. The results are discussed in terms of L1 and L2 transfer, whereby the transparency of written BM and the structured way in which reading is taught in BM facilitates performance on phonological tasks in English. This has implications for identifying children with phonologically based reading difficulties. Copyright © 2002 John Wiley & Sons, Ltd.
Alcohol abuse and dysfunctional eating in adolescent girls: The influence of individual differences in sensitivity to reward and punishment
Authors: Loxton Natalie J. , Dawe Sharon 
Published: August 2002

AbstractObjectiveAn unusually high comorbidity of eating disorders and alcohol abuse has been found in clinical and community samples of young women. This paper proposes that individual differences in sensitivity to reward and punishment may influence the propensity of young women to engage in dysfunctional eating and drinking behaviour.MethodThe Drive for Thinness scale, the Alcohol Use Disorders Identification Test and the BIS/BAS scales were administered to 232 high school girls.ResultsHeightened sensitivity to reward was the better predictor of alcohol misuse while heightened sensitivity to both reward and punishment was predictive of dysfunctional eating. When categorised by group, alcohol abusing, dysfunctional eating, and comorbid girls reported greater sensitivity to reward than non‐disordered girls. Girls with dysfunctional eating with and without comorbid alcohol abuse reported greater sensitivity to punishment than alcohol abusing only girls.DiscussionThese findings suggest that girls who abuse alcohol and have dysfunctional eating may share a vulnerability to heightened sensitivity to reward, yet be differentiated by sensitivity to punishment. © 2001 by John Wiley & Sons, Inc. Int J Eat Disord 29: 455–462, 2001.
Core beliefs and bulimic symptomatology in non‐eating‐disordered women: The mediating role of borderline characteristics
Authors: Meyer Caroline , Leung Newman , Feary Rachel , Mann Baljit 
Published: August 2002

AbstractObjectiveTo establish whether borderline personality disorder symptoms play a mediating role in the relationship between early maladaptive schemata and bulimic symptomatology, using a nonclinical sample.MethodSixty‐one female undergraduate students completed the Bulimic Investigatory Test, Edinburgh (BITE), the Borderline Syndrome Index (BSI), and the short form of the Young Schema Questionnaire (YSQ).ResultsBorderline symptoms were found to be a perfect mediator in the relationship between defectiveness/shame beliefs and bulimic symptomatology.ConclusionsA model is proposed suggesting that the functional utility of bulimic behaviors might be in counteracting the negative emotions associated with borderline symptoms. © 2001 by John Wiley & Sons, Inc. Int J Eat Disord 30: 434–440, 2001.
Self‐healing in networks with multiple reliability classes
Authors: Kitami Tokuhiro , Takasawa Jun 
Published: August 2002

AbstractSelf‐healing has been investigated as a technique for efficient path failure restoration in VP‐based networks. This paper discusses self‐healing in networks with multiple reliability classes, and evaluates restoration performance of different failure recovery procedures that introduce priority orders in the failure recovery process based on the reliability class for each failed path. The authors present a composite‐type restoration procedure in which preplanned‐type and flooding‐type procedures are combined. This paper also presents a bumping added‐type restoration procedure. The authors evaluated the performance of the above proposed techniques assuming various failure modes. The simulation results revealed that the proposed methods show improved performance. In addition, we propose an enhanced technique that introduces a subsidiary priority criterion in the paths belonging to the same reliability class, in order to increase the number of paths to be recovered. © 2001 Scripta Technica, Electron Comm Jpn Pt 1, 84(7): 1–17, 2001