bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis of 18F labelled FK960, a candidate anti‐dementia drug, and PET studies in conscious monkeys
Authors: Murakami Yoshihiro , Nishimura Shintaro , Noda Akihiro , Harada Norihiro , Tsukada Hideo 
Published: December 2002

AbstractThe present study demonstrated the synthesis and in vivo study of 18F‐labeled N‐(4‐acetyl‐1‐piperazinyl)‐p‐fluorobenzamide (FK960) which is a novel anti‐dementia drug candidate. [18F]FK960 was prepared by a one‐pot, three reaction sequence, using nucleophilic fluorination, with an automated synthetic apparatus using either ethyl‐4‐trimethylammonium triflate (1a) or ethyl‐4‐nitrobenzoate (1b) as the precursor for labeling. Though 1a gave a higher yield, the specific activity was 50–100 fold higher with 1b. The radiochemical yield of [18F]FK960 was 7–15% (EOB) and the specific activity ranged from 2.0–60.2 GBq/μmol depending on the amount of F‐18 used. The synthesis time was 2.2–2.9 h. The obtained [18F]FK960 was injected into 3 conscious monkeys (100–120 MBq/kg body weight), and distribution images and pharmacokinetic data for [18F]FK960 showed similar uptake in different brain regions and 3‐fold higher levels of [18F]FK960 in blood relative to brain. Copyright © 2002 John Wiley & Sons, Ltd.
Reaction of [18F]4‐fluorobenzenediazonium cations with cysteine or the cysteinyl group: preparation of 18F‐labeled S‐aryl‐cysteine and a radiolabeled peptide
Authors: Patt J. T. , Patt M. 
Published: December 2002

AbstractA reaction route for the preparation of no‐carrier‐added (n.c.a.) [18F]S‐4‐fluorophenylcysteine 7 via the [18F]‐4‐fluorobenzenediazonium ion 4 is described. The key step in this radiosynthesis is the reaction of 4 with cysteine forming [18F]4‐fluorophenyldiazocysteine 6, which is subsequently converted into 7 by irradiation with 366 nm light. 4 was synthesized by reacting 1,4‐dinitrobenzene 1 with [18F]‐fluoride in acetonitrile in a PEEK‐capillary in a microwave oven. After dilution of the reaction mixture with methanol, the resulting [18F]4‐fluoro‐1‐nitrobenzene 2 was submitted to reduction by means of H2 with Pd on C catalyst. The resulting [18F]4‐fluoroaniline 3 was purified by HPLC and diazotized to 4. The preparation of 4 was optimized with regard to yield and purity. The radiochemical yield of 6 was >90% (based on 3) while after UV irradiation and HPLC purification 45% of 7 (based on 3) was obtained (yields corrected for decay). The suitability of this method for labeling peptides with fluorine‐18 was demonstrated by application to the tripeptide, glutathione (GSH; γ‐L‐glutamyl‐L‐cysteinyglycine) 8. Copyright © 2002 John Wiley & Sons, Ltd.
Synthesis of radiolabeled O6‐benzylguanine derivatives as new potential PET tumor imaging agents for the DNA repair protein O6‐alkylguanine‐DNA alkyltransferase
Authors: Zheng Qi‐Huang , Liu Xuan , Fei Xiangshu , Wang Ji‐Quan , Ohannesian David W. , Erickson Leonard C. , Stone K. Lee , Martinez Tanya D. , Miller Kathy D. , Hutchins Gary D. 
Published: December 2002

AbstractNovel radiolabeled O6‐benzylguanine derivatives, 2‐amino‐6‐O‐[11C]‐[(methoxymethyl)benzyloxy]‐9‐benzyl purines ([11C]p‐O6‐AMBP, 1a; [11C]m‐O6‐AMBP, 1b; [11C]o‐O6‐AMBP, 1c), have been synthesized for evaluation as new potential positron emission tomography (PET) tumor imaging agents for the DNA repair protein, O6‐alkylguanine‐DNA alkyltransferase (AGT). The appropriate precursors for radiolabeling were obtained in three steps from starting material 2‐amino‐6‐chloropurine with moderate to excellent chemical yields. Tracers were prepared by O‐[11C]methylation of hydroxymethyl precursors using [11C]methyl triflate. Pure target compounds were isolated by solid‐phase extraction (SPE) purification procedure in 45–60% radiochemical yields (decay corrected to the end of bombardment), and a synthesis time of 20–25min. Copyright © 2002 John Wiley & Sons, Ltd.
Synthesis of tertiary 14C‐labelled nonylphenol isomers
Authors: Vinken Ralph , Schmidt Burkhard , Schäffer Andreas 
Published: December 2002

AbstractThe ring‐14C‐labelled p‐nonylphenol (NP) isomers 4(3′,5′‐dimethyl‐3′‐heptyl)‐phenol (p353NP), 4(3′,6′‐dimethyl‐3′‐heptyl)‐phenol (p363NP) and 4(2′,6′‐dimethyl‐2′‐heptyl)‐phenol (p262NP) were synthesized for application in metabolism and sorption studies. Friedel–Crafts alkylation of 14C‐labelled phenol and the corresponding tertiary nonylalcohol with BF3 as catalyst was used. After clean‐up of p262NP and p363NP by preparative thin‐layer chromatography radiochemical yields amounted to 62.8 and 64.6%, specific radioactivities were 332 and 88.2 MBq/mmol, and radiochemical purities 97.6 and 99.0%. For both isomers, a large‐scale synthesis with non‐labelled phenol was additionally developed, which led to pure products (96 and 99%, respectively) without further purification steps. In the case of p353NP, which was formed as a diastereomeric mixture, the crude synthetic product had a radiochemical purity of 96.9% (radiochemical yield: 76.0%; specific activity: 298 MBq/mmol); thus, purification was not necessary. All products were characterized by means of gas chromatography‐mass spectroscopy, 1H‐ and 13C‐NMR, as well as IR. Copyright © 2002 John Wiley & Sons, Ltd.
Neural cell adhesion molecule‐mediated neurite outgrowth is repressed by overexpression of HES‐1
Authors: Jessen Ulla , Novitskaya Vera , Walmod Peter S. , Berezin Vladimir , Bock Elisabeth 
Published: December 2002

AbstractThe neural cell adhesion molecule (NCAM) stimulates neurite outgrowth by activating intracellular signaling cascades. We investigated the role of the transcriptional repressor HES‐1 in NCAM‐dependent neurite outgrowth by estimating neurite extension from PC12‐E2 cells grown in coculture with NCAM‐negative or NCAM‐positive fibroblasts. PC12‐E2 cells were transiently transfected with an expression plasmid encoding HES‐1. We found that expression of HES‐1 inhibited NCAM‐dependent neurite outgrowth. Treatment with arachidonic acid (an important messenger in NCAM‐dependent signaling) restored NCAM‐induced neurite outgrowth inhibited by HES‐1. These results suggest that HES‐1 is a regulator of intracellular signal transduction stimulated by cell adhesion molecules involved in neurite outgrowth. © 2002 Wiley‐Liss, Inc.
Expression of brain‐derived neurotrophic factor mRNA in rat hippocampus after treatment with antipsychotic drugs
Authors: Bai Ou , Chlan‐Fourney Jennifer , Bowen Rudy , Keegan David , Li Xin‐Min 
Published: December 2002

AbstractTypical and atypical antipsychotic drugs, though both effective, act on different neurotransmitter receptors and are dissimilar in some clinical effects and side effects. The typical antipsychotic drug haloperidol has been shown to cause a decrease in the expression of brain‐derived neurotrophic factor (BDNF), which plays an important role in neuronal cell survival, differentiation, and neuronal connectivity. However, it is still unknown whether atypical antipsychotic drugs similarly regulate BDNF expression. We examined the effects of chronic (28 days) administration of typical and atypical antipsychotic drugs on BDNF mRNA expression in the rat hippocampus using in situ hybridization. Quantitative analysis revealed that the typical antipsychotic drug haloperidol (1 mg/kg) down‐regulated BDNF mRNA expression in both CA1 (P < 0.05) and dentate gyrus (P < 0.01) regions compared with vehicle control. In contrast, the atypical antipsychotic agents clozapine (10 mg/kg) and olanzapine (2.7 mg/kg) up‐regulated BDNF mRNA expression in CA1, CA3, and dentate gyrus regions of the rat hippocampus compared with their respective controls (P < 0.01). These findings demonstrate that the typical and atypical antipsychotic drugs differentially regulate BDNF mRNA expression in rat hippocampus. © 2002 Wiley‐Liss, Inc.
Dysmyelination induced in vitro by IgM antisulfatide and antigalactocerebroside monoclonal antibodies
Authors: Rosenbluth Jack , Moon David 
Published: December 2002

AbstractAntiglycolipid antibodies cause a distinctive form of dysmyelination in vivo characterized by marked widening of the myelin period. Such “expanded” or “wide‐spaced” myelin occurs in peripheral nerves in certain paraproteinemias and in the CNS in multiple sclerosis. We have used an in vitro system to reproduce this pathology under controlled conditions to assess the role of antibody specificity and class and the need for cofactors in generating this kind of lesion in peripheral myelin. Schwann cell myelin formed in vitro around dorsal root ganglion cell axons was exposed for 3–14 days to hybridoma cells that produce specific monoclonal antibodies. Typical wide‐spaced myelin developed after exposure to either O4, which produces an IgM antisulfatide antibody, or O1, which produces an IgM antigalactocerebroside antibody. In both cases, the effect was apparent by three days in paranodal as well as internodal myelin, especially in the outer lamellae. This change did not depend on the presence of complement or macrophages in the cultures. Exposure to anti‐GalC hybridoma cells, which produce an IgG3 antiglycolipid antibody, did not produce wide‐spaced myelin, nor did exposure to hybridoma cells that secrete IgM antibodies directed against a non‐myelin antigen. The location and rapidity of the pathologic changes seen after O4 or O1 are consistent with penetration of the antibodies through the external mesaxon of already formed myelin and then between compact lamellae, progressively spreading them apart in the centripetal direction. This in vitro model shows that either of two specific monoclonal IgM antiglycolipid antibodies can alone reproduce a well known form of myelin pathology under defined conditions. © 2002 Wiley‐Liss, Inc.
Limited growth of severed CNS axons after treatment of adult rat brain with hyaluronidase
Authors: Moon Lawrence D. F. , Asher Richard A. , Fawcett James W. 
Published: December 2002

AbstractMany chondroitin sulfate proteoglycans (CSPGs) have been shown to influence CNS axon growth in vitro and in vivo. These interactions can be mediated through the core protein or through the chondroitin sulfate (CS) glycosaminoglycan (GAG) side chains. We have shown previously that degrading CS GAG side chains using chondroitinase ABC enhances dopaminergic nigrostriatal axon regeneration in vivo. We test the hypothesis that interfering with complete CSPGs also limit axon growth in vivo. Neurocan, versican, aggrecan, and brevican CSPGs may be anchored within extracellular matrix through binding to hyaluronan glycosaminoglycan. We examine whether degradation of hyaluronan using hyaluronidase might release these inhibitory CSPGs from the extracellular matrix and thereby enhance regeneration of cut nigrostriatal axons. Anesthetized adult rats were given knife cut lesions of the right hemisphere nigrostriatal tract and cannulae were secured transcranially thereby allowing repeated perilesional infusion of saline or saline containing hyaluronidase once daily for 10 days post‐axotomy. Eleven days post‐transection brains from animals under terminal anesthesia were recovered for histological evaluation. Effective delivery of substance was inferred from the observed reduction in perilesional immunoreactivity for neurocan and versican after treatment with hyaluronidase (relative to saline). Immunolabeling using antibodies against tyrosine hydroxylase was used to examine the response of cut dopaminergic nigral neurons. After transection and treatment with saline, dopaminergic nigral neurons sprouted in a region lacking astrocytes, neurocan and versican. Axons did not regenerate into the lesion surround that contained astrocytes and abundant neurocan and versican. After transection and treatment with hyaluronidase, there was a significant increase in the number of cut dopaminergic nigral axons growing up to 800 μm anterior to the site of transection. However, cut dopaminergic nigral axons still did not regenerate into the lesion surround that contained reduced (albeit residual) neurocan and versican immunoreactivity. Thus, partial degradation of hyaluronan and chondroitin sulfate and depletion of hyaluronan‐binding CSPGs enhances local sprouting of cut CNS axons, but long‐distance regeneration fails in regions containing residual hyaluronan‐binding CSPGs. Hyaluronan, chondroitin sulfate and hyaluronan‐binding CSPGs therefore likely contribute toward the failure of spontaneous axon regeneration in the injured adult mammalian brain and spinal cord. © 2002 Wiley‐Liss, Inc.
mRNA expression of ephrins and Eph receptor tyrosine kinases in the neonatal and adult mouse central nervous system
Authors: Liebl Daniel J. , Morris Carol J. , Henkemeyer Mark , Parada Luis F. 
Published: December 2002

AbstractEphrins and Eph receptors are a family of molecules that have been implicated in axonal pathfinding. A unique feature of B‐class ephrins and Eph receptors is their ability to transmit bidirectional signals in both ephrin‐ and Eph receptor‐expressing cells upon cell–cell contact. These signals can lead to cytoskeletal alterations that have been attributed to regulating neuronal growth responses. Examination of gene‐target knockout mice has supported this hypothesis, revealing numerous developmental defects in the nervous systems of mice mutant for both B‐class ephrins and Eph receptors. To examine the potential scope of action for these genes in the nervous system, we have used in situ hybridization to study the mRNA expression of ephrins (B1, B2, and B3) and Eph receptors (B1, B2, B3, A4) in neonatal and adult mice. We found ephrins and Eph receptors to be expressed throughout the CNS. Expression was observed in the epithelium and migratory regions of the neonate and adult tissues as well as in discrete regions of high plasticity, including the adult olfactory bulb, hippocampus, and cerebellum. These studies suggest additional potential roles for these molecules in the postnatal and adult CNS and will serve as a guide in the detailed evaluation of mutant mice. © 2002 Wiley‐Liss, Inc.
Early programmed cell death in human NT2 cell cultures during differentiation induced by all‐trans‐retinoic acid
Authors: Guillemain I. , Fontès G. , Privat A. , Chaudieu I. 
Published: December 2002

AbstractPrevious studies have demonstrated that programmed cell death takes place at different stages during the development of the CNS in vivo. Our purpose in this study was to detect early programmed cell death associated with the induction of differentiation by retinoic acid (RA) in the NT2 cell line. By using the annexin V labeling as a marker of apoptosis, a significant apoptotic cell death was quantified during the third and the fourth days of the RA treatment. Double‐labeling studies using the staining of the genomic DNA strand breaks with the terminal deoxyribosyl‐transferase‐mediated dUTP nick end‐labeling (TUNEL) assay and either nestin or microtubule‐associated protein 2 (MAP2) showed that 1) the early apoptotic cell death affected mostly nestin‐positive cells and 2) after 8 days of differentiation, although cells with neuronal phenotypes are present, no colabeled TUNEL/MAP2 cells were detected. With regard to the neuronal protein MAP2, we observed discrete immunolabeling of a few NT2 cells as early as day 3 of the differentiation and a significant emergence of MAP2‐immunopositive cells at days 6–8. Thus, our results show that, when as a whole the differentiating NT2 cell population is considered, 1) the apoptotic cell death observed during the third day of differentiation occurs mostly in undifferentiated cells, 2) this process coincides with the first detection of the neuronal phenotype in NT2 cell cultures, and 3) the end of the cell death period in NT2 cell cultures is marked by both the accumulation of MAP2‐positive cells and the beginning of expression of the Bcl‐2 protein in the cultures. © 2002 Wiley‐Liss, Inc.
Molecular identity, synaptic localization, and physiology of calcium channels in retinal bipolar cells
Authors: Berntson Amy , Taylor W. Rowland , Morgans Catherine W. 
Published: December 2002

AbstractBipolar cells convey information through the retina via graded changes in their membrane potential and modulate transmitter release through the influx of calcium via L‐type calcium channels. However, the molecular identity of the α1 subunit has not been confirmed. We report the presence of the newly cloned α1F subunit in mouse bipolar cell synaptic terminals. The α1F subunits are localized to hot spots, possibly corresponding to active zones. We also report the physiological properties of two calcium currents present in mouse bipolar cells, a low‐voltage‐activated L‐type current and a low‐voltage‐activated T‐type calcium current. The physiological properties of the T‐type current suggest that it is completely inactivated under physiological conditions. The L‐type current may be mediated by the α1F subunit, and influx of calcium through the α1F channel may control neurotransmitter release from the bipolar cell terminal. © 2002 Wiley‐Liss, Inc.
Mouse brains deficient in H‐ferritin have normal iron concentration but a protein profile of iron deficiency and increased evidence of oxidative stress
Authors: Thompson Khristy , Menzies Sharon , Muckenthaler Martina , Torti Frank M. , Wood Teresa , Torti Suzy V. , Hentze Matthias W. , Beard John , Connor James 
Published: December 2002

AbstractSeveral neurodegenerative disorders such as Parkinson's Disease (PD) and Alzheimer's Disease (AD) are associated with elevated brain iron accumulation relative to the amount of ferritin, the intracellular iron storage protein. The accumulation of more iron than can be adequately stored in ferritin creates an environment of oxidative stress. We developed a heavy chain (H) ferritin null mutant in an attempt to mimic the iron milieu of the brain in AD and PD. Animals homozygous for the mutation die in utero but the heterozygotes (+/−) are viable. We examined heterozygous and wild‐type (wt) mice between 6 and 8 months of age. Macroscopically, the brains of +/− mice were well formed and did not differ from control brains. There was no evidence of histopathology in the brains of the heterozygous mice. Iron levels in the brain of the +/− and wild‐type (+/+) mice were similar, but +/− mice had less than half the levels of H‐ferritin. The other iron management proteins transferrin, transferrin receptor, light chain ferritin, Divalent Metal Transporter 1, ceruloplasmin, were increased in the +/− mice compared to +/+ mice. The relative amounts of these proteins in relation to the iron concentration are similar to that found in AD and PD. Thus, we hypothesized that the brains of the heterozygote mice should have an increase in indices of oxidative stress. In support of this hypothesis, there was a decrease in total superoxide dismutase (SOD) activity in the heterozygotes coupled with an increase in oxidatively modified proteins. In addition, apoptotic markers Bax and caspase‐3 were detected in neurons of the +/− mice but not in the wt. Thus, we have developed a mouse model that mimics the protein profile for iron management seen in AD and PD that also shows evidence of oxidative stress. These results suggest that this mouse may be a model to determine the role of iron mismanagement in neurodegenerative disorders and for testing antioxidant therapeutic strategies. © 2002 Wiley‐Liss, Inc.
Cells exposed to a huntingtin fragment containing an expanded polyglutamine tract show no sign of ion channel formation: Results arguing against the ion channel hypothesis
Authors: Nørremølle Anne , Grunnet Morten , Hasholt Lis , Sørensen Sven Asger 
Published: December 2002

AbstractIon channels formed by expanded polyglutamine tracts have been proposed to play an important role in the pathological processes leading to neurodegeneration in Huntington's disease and other CAG repeat diseases. We tested the capacity of a huntingtin fragment containing an expanded polyglutamine tract to form ion channels in two cell types. Whole cell current from Xenopus oocytes was recorded using two‐electrode voltage‐clamp technique, and whole cell current from CHO‐K1 cells was recorded by patch‐clamp technique. The fragment with an expanded polyglutamine sequence induced no change in the currents recorded in any of the two expression systems, indicating no changes in ion channel activity. The results therefore argue against the proposed hypothesis of expanded polyglutamines forming ion channels. © 2002 Wiley‐Liss, Inc.
Effects of tumor necrosis factor‐alpha central administration on hippocampal damage in rat induced by amyloid beta‐peptide (25–35)
Authors: Stepanichev Mikhail Yu. , Zdobnova Irina M. , Yakovlev Alexander A. , Onufriev Mikhail V. , Lazareva Natalia A. , Zarubenko Irina I. , Gulyaeva Natalia V. 
Published: December 2002

AbstractMale Wistar rats received unilateral intrahippocampal injections of 3 nmol (3.18 μg) aggregated Aβ(25–35), intracerebroventricular bilateral injections of 0.5 μg human recombinant TNFα or both (Aβ(25–35) + TNFα‐treated animals). Seven days after the surgery brain sections were stained with cresyl violet (Nissl), for fragmented DNA (TUNEL), glial fibrillar acidic protein (GFAP) and isolectin B4‐reactive microglia. In addition, caspase‐3 activity in brain regions was measured fluorometrically. The morphology of the hippocampus after the injection of Aβ(25–35) or both Aβ(25–35) and TNFα (but not TNFα alone) showed cell loss in the CA1 pyramidal cell layer. The extension of neuronal degeneration measured in the CA1 field was significantly larger in Aβ(25–35)‐treated groups compared to the contralateral hemisphere of both vehicle‐treated controls and animals injected with TNFα alone. TNFα augmented the Aβ(25–35)‐induced damage, significantly increasing the extension of degenerating area. Administration of Aβ(25–35) caused reactive gliosis in the ipsilateral hemisphere as demonstrated by upregulation of GFAP expression and the presence of hypertrophic astrocytes in the hippocampus. This effect was much more prominent in the hippocampi of rats treated with Aβ(25–35) + TNFα but absent after administration of TNFα alone. In both Aβ(25–35)‐treated groups, the damaged area of the hippocampal CA1 field and lateral band of dentate gyrus displayed many darkly stained round isolectin B4‐positive phagocyte‐like microglial cells. Sparse TUNEL‐positive nuclei were found in the hippocampi of rats treated with Aβ(25–35) alone or together with TNFα, but not in the control brain sections or in brain sections of TNFα‐injected animals. The activity of caspase‐3 increased significantly in the ipsilateral hippocampus after the injection of Aβ(25–35). Surprisingly, administration of TNFα into the cerebral ventricles prevented this Aβ(25–35)‐induced increase in hippocampal caspase‐3 activity. The results are discussed from the perspective of dual (neuroprotective and neurodestructive) roles of TNF in the brain. © 2002 Wiley‐Liss, Inc.
Effect of thoughtful preparation on the catheterization of children undergoing investigative studies
Authors: Gladh Gunilla 
Published: December 2002

AbstractAims:To evaluate an anesthetic sedation free method of transurethral catheterization in children.Methods:The child and his or her parents are thoroughly prepared for the procedure by means of written and oral child‐adapted information and practical instructions. To evaluate this routine, a simple questionnaire was given to 115 consecutive children undergoing transurethral catheterization.Results:The questionnaire was returned by 99 children (86%). Most children and parents (95) found the preparation“good”or“very good”and tolerated the catheterization procedure well. Only six children reported the catheterization to be“very painful”(without requiring that the procedure was terminated). Complications, such as urgency, smarting pain during voidings, or both, after withdrawal of the catheter, occurred in 12 children and urinary tract infections in 3. Unexpectedly, girls were affected more often than boys.Conclusions:Careful preparation of children and their parents allows the great majority of diagnostic studies that require urethral catheterization to be accomplished without anesthesia. Neurourol. Urodynam. 22:58–61, 2003. © 2003 Wiley‐Liss, Inc.