bluuebunny/crossref_metadata_2025 huggingface dataset:
Transient uterine myometrial contraction associated with moles
Authors: Hatakenaka Masamitsu , Yoshimitsu Kengo , Adachi Toshisada , Matsuda Takao , Wake Norio , Honda Hiroshi
Published: January 2004

Purpose

To examine the incidence of transient distortion of uterine central tissue and myometrial hypointense areas observed on MR images in women with clinically suspicious moles.

Materials and Methods

The study population consisted of six women aged 15–47 years with clinically suspicious moles (hydatidiform mole in four, invasive mole in one, and microscopic mole in one). The control study population was 105 reproductive‐age women (18–52 years) without uterine malignancy, gestational trophoblastic disease, or pregnancy. MR images were analyzed to check for discrepancies of the uterine central tissue configuration. If a discrepancy was observed, the myometrial hypointense area, its diameter, and changes in its shape and location were analyzed.

Results

Differences in uterine central tissue configuration and hypointense areas were observed in all six patients. In the control study, only seven cases showed uterine endometrial distortion, and five exhibited hypointense areas. These areas disappeared, changed in shape, or other hypointense areas appeared on subsequent MR images. Significant differences (P < 0.01) in the incidence of uterine central tissue distortion and hypointense areas, and in their maximum diameter between the study and the control groups were observed.

Conclusion

Uterine myometrial hypointense areas with central tissue distortion, most likely due to transient myometrial contraction, are frequently seen in women with clinically suspicious moles. J. Magn. Reson. Imaging 2004;19:182–187. © 2004 Wiley‐Liss, Inc.
The utility of MRCP in preoperative mapping of biliary anatomy in adult‐to‐adult living related liver transplant donors
Authors: Limanond Piyaporn , Raman Steven S. , Ghobrial R. Mark , Busuttil Ronald W. , Lu David S. K.
Published: January 2004

Purpose

To assess the utility of magnetic resonance cholangiopancreatography (MRCP) in preoperative mapping of biliary anatomy in adult‐to‐adult living related liver transplant (LRLT) donors.

Materials and Methods

From 57 potential donors with preoperative MRCP, 27 cases (16 men, 11 women, age range 22–51 years, mean 37.2 years) underwent right lobe resection and had intraoperative cholangiography (IOC) for comparison. The MRCP and IOC reports were retrospectively reviewed in all 27 cases. The MRCP was performed on 1.5 Tesla MR magnets using breath‐hold heavily T2‐weighted sequences in axial/coronal thin sections, and variable‐thickness rotating slabs. The accuracy of preoperative MRCP for biliary mapping in potential LRLT donors was analyzed compared to the IOC findings.

Results

Of 27 donors, 26 (96.3%) had MRCP which showed adequate information of central intrahepatic biliary anatomy. Of these, 19 had normal bifurcation confirmed by IOC, and single biliary anastomosis was created in the recipient at transplantation. MRCP correctly predicted 17 of 19 normal cases (sensitivity for normals: 89.5%). In seven donors with variant biliary anatomy, two separate biliary anastomoses were performed in the recipient. MRCP correctly predicted five of seven variants (sensitivity for variants: 71.4%). Overall, MRCP had an accuracy 84.6% (22/26).

Conclusions

MRCP has potential in the preoperative assessment of nondilated bile ducts in LRLT donors, however further improvements are desired to increase its quality and accuracy. J. Magn. Reson. Imaging 2004;19:209–215. © 2004 Wiley‐Liss, Inc.
Time‐resolved contrast‐enhanced three‐dimensional pulmonary MR‐angiography: 1.0 M gadobutrol vs. 0.5 M gadopentetate dimeglumine
Authors: Fink Christian , Bock Michael , Kiessling Fabian , Lichy Matthias Philipp , Krissak Radko , Zuna Ivan , Schmähl Astrid , Delorme Stefan , Kauczor Hans‐Ulrich
Published: January 2004

Purpose

To compare contrast characteristics and image quality of 1.0 M gadobutrol with 0.5 M Gd‐DTPA for time‐resolved three‐dimensional pulmonary magnetic resonance angiography (MRA).

Materials and Methods

Thirty‐one patients and five healthy volunteers were examined with a contrast‐enhanced time‐resolved pulmonary MRA protocol (fast low‐angle shot [FLASH] three‐dimensional, TR/TE = 2.2/1.0 msec, flip angle: 25°, scan time per three‐dimensional data set = 5.6 seconds). Patients were randomized to receive either 0.1 mmol/kg body weight (bw) or 0.2 mmol/kg bw gadobutrol, or 0.2 mmol/kg bw Gd‐DTPA. Volunteers were examined three times, twice with 0.2 mmol/kg bw gadobutrol using two different flip angles and once with 0.2 mmol/kg bw Gd‐DTPA. All contrast injections were performed at a rate of 5 mL/second. Image analysis included signal‐to‐noise ratio (SNR) and contrast‐to‐noise ratio (CNR) measurements in lung arteries and veins, as well as a subjective analysis of image quality.

Results

In patients, significantly higher SNR and CNR were observed with Gd‐DTPA compared to both doses of gadobutrol (SNR: 35–42 vs.17–25; CNR 33–39 vs. 16–23; P ≤ 0.05). No relevant differences were observed between 0.1 mmol/kg bw and 0.2 mmol/kg bw gadobutrol. In volunteers, gadobutrol and Gd‐DTPA achieved similar SNR and CNR. A significantly higher SNR and CNR was observed for gadobutrol‐enhanced MRA with an increased flip angle of 40°. Image quality was rated equal for both contrast agents.

Conclusion

No relevant advantages of 1.0 M gadobutrol over 0.5 M Gd‐DTPA were observed for time‐resolved pulmonary MRA in this study. Potential explanations are T2/T2*‐effects caused by the high intravascular concentration when using high injection rates. J. Magn. Reson. Imaging 2004;19:202–208. © 2004 Wiley‐Liss, Inc.
Retinoic acid‐mediated induction of neurons and glial cells from human umbilical cord‐derived hematopoietic stem cells
Authors: Jang Y.K. , Park J.J. , Lee M.C. , Yoon B.H. , Yang Y.S. , Yang S.E. , Kim S.U.
Published: January 2004

Recent studies reporting trans‐differentiation of mononucleated cells derived from human umbilical cord blood into neuronal cells aroused interest among investigators for their clinical implication and significance in regenerative medicine. In the present study, purified populations of hematopoietic stem cells were isolated via magnetic bead sorting and fluorescence‐activated cell sorter (FACS) using a specific CD133 antibody, a cell type‐specific marker for hematopoietic stem cells, and grown in culture in the presence of retinoic acid (RA). CD133+ hematopoietic stem cells expressed neuronal and glial phenotypes after RA treatment. RT‐PCR analysis indicated that the RA treated CD133+ cells expressed mRNA transcripts for ATP‐binding cassettes transporter ABCG2 (a universal stem cell marker), nestin (a specific cell type marker for neural stem cells), Musashi1 (a specific marker for neural stem cells) and RA receptors (RAR) including RAR‐α, RAR‐β, and retinoid X receptor (RXR)‐γ. RA‐treated CD133+ cells expressed mRNA transcripts for neuron‐specific markers neurofilament proteins (NF‐L, ‐M, ‐H) and synaptophysin as determined by RT‐PCR, structural proteins characteristic of neurons including tubulin β III and neuron specific enolase (NSE) by Western blot, and neuron‐specific markers NeuN and microtubule‐associated protein‐2 (MAP2) by immunocytochemistry. RA‐treated CD133+ cells also expressed the astrocyte‐specific marker glial fibrillary acidic protein (GFAP), as demonstrated by RT‐PCR, Western blot, and immunocytochemistry. In addition, RA‐treated CD133+ cells expressed cell type‐specific markers for oligodendrocytes including myelin basic protein (MBP) as shown by RT‐PCR, proteolipid protein (PLP) by Western blot analysis, and cyclic nucleotide phosphodiesterase (CNPase) by immunostaining. Upregulated expression of several basic helix‐loop‐helix (bHLH) transcription factors important for early neurogenesis, including Otx2, Pax6, Wnt1, Olig2, Hash1 and NeuroD1, was also demonstrated in CD133+ cells after RA treatment. These results indicate that human cord blood‐derived CD133+ hematopoietic stem cells could trans‐differentiate into neural cell types of neuron‐like cells, astrocytes, and oligodendrocytes by RA treatment. © 2003 Wiley‐Liss, Inc.
Patterns of Jagged1, Jagged2, Delta‐like 1 and Delta‐like 3 expression during late embryonic and postnatal brain development suggest multiple functional roles in progenitors and differentiated cells
Authors: Irvin Dwain K. , Nakano Ichiro , Paucar Andreas , Kornblum Harley I.
Published: January 2004

The Notch‐DSL signaling system, consisting of multiple receptors and ligands, inhibits neurogenesis and promotes gliogenesis during embryonic development, but the specific function of the various ligands and receptors at later developmental stages are unknown. Here, we examined the expression pattern of four Delta, Serrate and Lag‐2 (DSL) ligands, Jagged1, Jagged2, Delta‐like1 (Dl1) and Delta‐like 3 (Dl3), in late embryonic and postnatal rat brain by in situ hybridization. In late embryos, Jagged1, Dl1 and Dl3 mRNAs were present in the periventricular germinal epithelia, but this expression diminished during postnatal ages. Jagged1 mRNA was also expressed in the inner aspect of the dentate gyrus at early postnatal times. Dl3 was detectable in the external granule cell layer (EGL) of the cerebellum, another site of postnatal neurogenesis. Jagged2 mRNA was expressed in virtually all postnatal neurons. Jagged1 mRNA was highly expressed in several brain nuclei during postnatal development, with lower levels of expression in other grey matter regions. In white matter, Dl1 and Dl3 mRNAs were expressed during the first week of postnatal development but only the expression of Dl1 mRNA persisted through the second week. Dl1 mRNA was present at lower levels throughout grey matter during the first few weeks of development. Jagged1 mRNA was expressed in blood vessels, choroid plexus, and menninges throughout development and in the adult. Jagged2 mRNA was transiently expressed in cerebral blood vessels and choroid plexus during the first postnatal week. Taken together, these results support multiple and differing roles for the various ligands during and after central nervous system (CNS) development. © 2004 Wiley‐Liss, Inc.
Divalent cations modulate the activity of metabotropic glutamate receptors
Authors: Francesconi Anna , Duvoisin Robert M.
Published: January 2004

Metabotropic glutamate receptors (mGluRs) and calcium receptors (CaR) are closely related G protein‐coupled receptors (GPCRs). The similar structural and functional properties of mGluRs and CaRs include conserved amino acid residues involved in glutamate binding in mGluRs and Ca2+ binding in the CaR. Furthermore, recent findings have demonstrated that mGluRs can respond to high extracellular Ca2+ (Ca) whereas CaR activity is potentiated by L‐amino acids. We show that both mGluR1 and mGluR2 are activated by Ca in the absence of glutamate in the extracellular media. This activation by Ca is antagonized by Mg. Unlike the CaR, in which the intracellular carboxyl tail has been reported to be involved in Ca‐dependent activity, the carboxyl tail of mGluRs does not seem to play a role in mediating Ca actions. On the other hand, we find that preservation of disulfide bonds in the N‐terminal extracellular domain of mGluRs is essential for stimulation by Ca as well as glutamate. Because the mGluR1 EC50 for Ca is within the physiologic range of Ca2+ in the synaptic cleft, mGluR function is likely regulated by changes in divalent cations caused by synaptic activity under normal or pathologic conditions. © 2003 Wiley‐Liss, Inc.
TIEG1 facilitates transforming growth factor‐β‐mediated apoptosis in the oligodendroglial cell line OLI‐neu
Authors: Bender Herdis , Wang Ziyuan , Schuster Norbert , Krieglstein Kerstin
Published: January 2004

Transforming growth factor‐β (TGF‐β) plays an important role during the period of developmental cell death in the nervous system. Using the oligodendroglial precursor cell line OLI‐neu, we have previously established an in vitro system to analyze TGF‐β‐mediated cell death on the molecular level. We could show that the Krüppel‐like Zn‐finger transcription factor TIEG1 was up‐regulated after TGF‐β stimulation of OLI‐neu cells and mimicked TGF‐β effects in these cells; i.e., overexpression of TIEG1 in OLI‐neu cells induced apoptosis as shown by apoptosis ELISA, DNA fragmentation, and caspases‐3 activation. The apoptotic pathway seemed to be initiated by repressing the expression of the antiapoptotic protein Bcl‐XL. In contrast, the reporter activity of a SMAD consensus promoter was induced, whereas the promoter activity of the inhibitory SMAD7 was reduced, suggesting that SMAD‐dependent TGF‐β responses, such as TGF‐β‐induced apoptosis, are enhanced in the presence of TIEG1. © 2003 Wiley‐Liss, Inc.
ADAM (a disintegrin and metalloprotease) 12 is expressed in rat and human brain and localized to oligodendrocytes
Authors: Bernstein Hans‐Gert , Keilhoff Gerburg , Bukowska Alicja , Ziegeler Anke , Funke Sieglinde , Dobrowolny Henrik , Kanakis Dimitrios , Bogerts Bernhard , Lendeckel Uwe
Published: January 2004

ADAM12 is a member of the large family of multidomain metalloprotease‐disintegrins which possess cell‐binding and metalloprotease properties. Typically, ADAM12 is expressed in mesenchymal cells, developing and regenerating heart and skeletal muscle, bone as well as in certain tumours. This report shows by means of reverse transcriptase‐polymerase chain reaction (RT‐PCR) and immunohistochemistry that the protease ADAM12 is detectable in human and rat brain tissue as well as in cultured cells derived from rat brain. With the exception of a very few immunopositive pyramidal neurons in the developing rat brain, the cellular localization of ADAM12 was exclusively confined to oligodendroglial cells. Thus, ADAM12 may be regarded a new suitable marker for this cell type. © 2003 Wiley‐Liss, Inc.
Amino‐ and carboxyl‐terminal mutants of presenilin 1 cause neuronal cell death through distinct toxic mechanisms: Study of 27 different presenilin 1 mutants
Authors: Hashimoto Yuichi , Tsukamoto Emi , Niikura Takako , Yamagishi Yohichi , Ishizaka Miho , Aiso Sadakazu , Takashima Akihiko , Nishimoto Ikuo
Published: January 2004

Presenilin (PS)1 and its mutants, which consist of the N‐terminal and C‐terminal fragments, cause certain familial forms of Alzheimer's disease (FAD). Our earlier studies found that FAD‐linked M146L‐PS1 causes neuronal cell death through nitrogen oxide synthase (NOS) and that FAD‐linked N141I‐PS2, another member of the PS family, causes neuronal cell death through NADPH oxidase. In this study, we examined 27 different FAD‐linked mutants of PS1, and found that PS1 mutants with mutations in the N‐terminal fragment caused NOS inhibitor (NOSI)‐sensitive neuronal cell death; in contrast, the PS1 mutants with mutations in the C‐terminal fragment caused NOSI‐resistant neuronal cell death. The former toxicity was resistant to the specific NADPH oxidase inhibitor apocynin and was inhibited by Humanin (HN), a newly identified neuroprotective factor against Alzheimer's disease (AD)‐relevant insults, but not by insulin‐like growth factor‐I (IGF‐I). In contrast, the latter toxicity was sensitive to apocynin and inhibited by both IGF‐I and HN. This study indicates for the first time that N‐ and C‐terminal fragment PS1 mutants can generate distinct neurotoxic signals, which will provide an important clue to the understanding of the entire array of neurotoxic signals generated by FAD‐causative mutations of PS1. © 2003 Wiley‐Liss, Inc.
Altered localization of Cav1.2 (L‐type) calcium channels in nerve fibers, Schwann cells, odontoblasts, and fibroblasts of tooth pulp after tooth injury
Authors: Westenbroek R.E. , Anderson N.L. , Byers M.R.
Published: January 2004

We have determined the localization of Cav1.2 (L‐Type) Ca2+ channels in the cells and nerve fibers in molars of normal or injured rats. We observed high levels of immunostaining of L‐type Ca2+ channels in odontoblast cell bodies and their processes, in fibroblast cell bodies and in Schwann cells. Many Cav1.2‐containing unmyelinated and myelinated axons were also present in root nerves and proximal branches in coronal pulp, but were usually missing from nerve fibers in dentin. Labeling in the larger fibers was present along the axonal membrane, localized in axonal vesicles, and in nodal regions. After focal tooth injury, there is a marked loss of Cav1.2 channels in injured teeth. Immunostaining of Cav1.2 channels was lost selectively in nerve fibers and local cells of the tooth pulp within 10 min of the lesion, without loss of other Cav channel or pulpal labels. By 60 min, Cav1.2 channels in odontoblasts were detected again but at levels below controls, whereas fibroblasts were labeled well above control levels, similar to upregulation of Cav1.2 channels in astrocytes after injury. By 3 days after the injury, Cav1.2 channels were again detected in nerve fibers and immunostaining of fibroblasts and odontoblasts had returned to control levels. These findings provide new insight into the localization of Cav1.2 channels in dental pulp and sensory fibers, and demonstrate unexpected plasticity of channel distribution in response to nerve injury. © 2003 Wiley‐Liss, Inc.
Neuritogenesis induced by vasoactive intestinal peptide, pituitary adenylate cyclase‐activating polypeptide, and peptide histidine methionine in SH‐SY5y cells is associated with regulated expression of cytoskeleton mRNAs and proteins
Authors: Héraud Céline , Hilairet Sandrine , Muller Jean‐Marc , Leterrier Jean‐François , Chadéneau Corinne
Published: January 2004

Vasoactive intestinal peptide (VIP) and the related peptides pituitary adenylate cyclase‐activating polypeptide (PACAP) and peptide histidine methionine (PHM) are known to regulate proliferation and/or differentiation in normal and tumoral cells. In this study, neuritogenesis in human neuroblastoma SH‐SY5Y cells cultured in serum‐free medium was induced by VIP, PACAP, and PHM. The establishment of this process was followed by the quantification of neurite length and branching and the expression of neurofilament mRNAs, neurofilament proteins, and other cytoskeletal protein markers of neuronal differentiation: neuron‐specific MAPs and β‐tubulin III. Neurite length and branching and the expression of most markers tested were increased by VIP and PACAP in a similar, although slightly different, fashion. In contrast, neuritic elongation induced by PHM was correlated with neither an increase in branching or neurofilament mRNAs nor a clear change in the expression of cytoskeleton proteins, with the exception of the stimulation by PHM of doublecortin, a microtubule‐associated marker of migrating neuroblasts. These findings are the first evidence from a human neuron‐like cell line for 1) a direct regulation of the metabolism of neurofilaments by VIP and PACAP and 2) the induction by PHM of neuritic processes of an apparent immature character. © 2003 Wiley‐Liss, Inc.
Proteomic analysis of protein changes developing in rat hippocampus after chronic antidepressant treatment: Implications for depressive disorders and future therapies
Authors: Khawaja Xavier , Xu Jun , Liang Jin‐Jun , Barrett James E.
Published: January 2004

It is recognized that monoamine reuptake inhibitors (MARIs) exert beneficial effects in the treatment of major depression and general anxiety disorder. The aim of this study was to identify proteins regulated by this class of antidepressant using a proteome differential profiling approach. Either venlafaxine or fluoxetine was administered systemically to adult rats for 2 weeks, and protein patterns from rat hippocampal cytosolic extracts were compared by two‐dimensional gel electrophoresis. Silver‐stained protein spots displaying differential expression were identified by mass spectrometry. Thirty‐three protein spots were modulated by both drug treatments compared to controls. The classification of several proteins that were sorted by function suggested convergent pathway activities for both MARIs at the post‐receptor level. These included proteins associated with neurogenesis (insulin like growth factor 1 (IGF‐1), glia maturation factor [GMF]‐β), outgrowth/maintenance of neuronal processes (hippocampal cholinergic neurostimulating peptide [HCNP], PCTAIRE‐3), and with neural regeneration/axonal guidance collapsin response mediator protein (CRMP‐2) systems. Other modulated proteins indicated an increase in neuronal vesicular cell trafficking and synaptic plasticity (Ras‐related protein 4a (Rab4a), Ras‐related protein 1b (Rab1b), heat shock protein 10 [HSP10]), as well as neurosteroidogenic (hydroxysteroid sulfotransferase A) and possible anti‐apoptotic (dimethylargininase‐1 L‐N,N‐dimethylarginine dimethylaminohydrolase‐1 [DDAH‐1], pyruvate dehydrogenase‐E1 [PDH‐E1], antioxidant protein‐2 [AOP‐2]) pathway‐mediated regulatory events. Parallel studies to investigate further the effects of venlafaxine and fluoxetine on adult hippocampal neurogenesis in vivo by quantitative bromodeoxyuridine immunolabeling revealed a significant drug‐induced increase in the proliferation rate and long‐term survivability of progenitor stem cells located in the subgranular zone. These data suggest that MARIs share wide‐ranging proteome changes within the hippocampal formation, beyond 5‐HT/NE neurotransmission. This may reflect long‐term functional adaptations required for antidepressant activity. © 2004 Wiley‐Liss, Inc.
Suppression of proliferation and neurite extension of human neuroblastoma SH‐SY5Y cells on immobilized Psathyrella velutina lectin
Authors: Kitamura Noriaki , Ikekita Masahiko , Hayakawa Satoru , Funahashi Hisayuki , Furukawa Kiyoshi
Published: January 2004

Glycoproteins from mammalian brain tissues contain unique N‐linked oligosaccharides terminating with β‐N‐acetylglucosamine residues. Lectin blot analysis of membrane glycoprotein samples from human neuroblastoma SH‐SY5Y cells showed that several protein bands bind to Psathylera velutina lectin (PVL), which interacts with β‐N‐acetylglucosamine‐terminating oligosaccharides. No lectin positive bands were detected by digestion with jack bean β‐N‐acetyl‐hexosaminidase or N‐glycanase before incubation with the lectin, indicating that the cells contain β‐N‐acetylglucosamine‐terminating N‐linked oligosaccharides. When cells were cultured in dishes with different concentrations of PVL, the cell proliferation was inhibited in a dose‐dependent manner. Similarly, the neurite extension, which was stimulated with nerve growth factor, was also inhibited in a manner dependent on the lectin dose. Cell proliferation and neurite extension were recovered by the addition of 10 mM N‐acetylglucosamine into the medium. Immunoblot analysis of the activation of mitogen‐activated protein (MAP) kinases and protein kinase C revealed that phosphorylation of 42‐kDa and 44‐kDa MAP kinases and 80‐kDa protein kinase C are inhibited when SH‐SY5Y cells are cultured in PVL‐coated dishes, but are restored by the addition of the haptenic sugar into the medium, indicating that MAP kinase and protein kinase C pathways are inhibited by interaction with immobilized PVL. These results indicate that β‐N‐acetylglucosamine‐terminating N‐linked oligosaccharides expressed on neural cells can induce intracellular signals upon binding to extracellular receptors, and are important for growth regulation of neural cells. © 2003 Wiley‐Liss, Inc.
Sulfate‐ and size‐dependent polysaccharide modulation of AMPA receptor properties
Authors: Chicoine Linda M. , Suppiramaniam Vishnu , Vaithianathan Thirumalini , Gianutsos Gerald , Bahr Ben A.
Published: January 2004

Previous work found evidence that α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA)‐type glutamate receptors interact with and are functionally regulated by the glycosaminoglycan heparin. The present study tested whether dextran species affect ligand binding, channel kinetics, and calcium permeability of AMPA receptors. Dextran sulfate of 500 kDa markedly reduced high affinity [3H]AMPA binding in solubilized hippocampal membranes. In isolated receptors reconstituted in a lipid bilayer, the same dextran sulfate prolonged the lifetime of open states exhibited by AMPA‐induced channel fluctuations. The large polysaccharide further changed the single channel kinetics by increasing the open channel probability five‐ to sixfold. Such modulation of channel activity corresponded with enhanced levels of calcium influx as shown in hippocampal neurons loaded with Fluo3AM dye. With an exposure time of <1 min, AMPA produced a dose‐dependent increase in intracellular calcium that was blocked by 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione disodium (CNQX). Dextran sulfate, at the same concentration range that modified ligand binding (EC50 of 5–10 nM), enhanced the AMPA‐induced calcium influx by as much as 60%. The enhanced influx was blocked by CNQX, although unchanged by the N‐methyl‐D‐aspartate (NMDA) receptor antagonist AP5. Confocal microscopy showed that the increase in calcium occurred in neuronal cell bodies and their processes. Interestingly, smaller 5–8‐kDa dextran sulfate and a non‐sulfated dextran of 500 kDa had little or no effect on the binding, channel, and calcium permeability properties. Together, these findings suggest that synaptic polysaccharide species modulate hippocampal AMPA receptors in a sulfate‐ and size‐dependent manner. © 2003 Wiley‐Liss, Inc.
A non‐peptide substance P antagonist (CP‐96,345) inhibits morphine‐induced NF‐κB promoter activation in human NT2‐N neurons
Authors: Wang Xu , Douglas Steven D. , Commons Kathryn G. , Pleasure David E. , Lai Jianping , Ho Chun , Bannerman Peter , Williams Marge , Ho Wenzhe
Published: January 2004

Opioids and the neuropeptide substance P (SP) modulate the expression of inflammatory cytokines and chemokines, which are under the control of nuclear factor κB (NF‐κB). We investigated whether the neurokinin‐1 receptor (SP receptor) pathway is biologically involved in morphine‐mediated modulation of NF‐κB promoter activation in a human neuronal cell line (NT2‐N) that expresses both the mu‐opioid receptor (MOR) and the SP receptor. Morphine significantly enhanced NF‐κB promoter‐directed luciferase activity in NT2‐N neurons. DAMGO, a selective mu‐opioid receptor agonist, also induced NF‐κB promoter activation. The induced activation of NF‐κB promoter by morphine or DAMGO was abolished not only by naltrexone (a opioid receptor antagonist) and CTAP (a selective, competitive mu‐opioid receptor antagonist), but also by CP‐96,345, a non‐peptide SP receptor antagonist. Investigation of the mechanism responsible for morphine‐induced activation of NF‐κB promoter in NT2‐N neurons demonstrated that morphine activates the SP promoter and induces SP expression in these cells. We also observed that SP activated NF‐κB promoter and that CP‐96,345 downregulated the expression of endogenous SP. Furthermore, dual immunofluorescent labeling revealed that there is co‐expression of NK‐1R and MOR in the processes of NT‐2N neurons. These results suggest that morphine, by activating MOR, engages a positive feedback loop between NK‐1R and SP. Activation of NK‐1R could then impact NF‐κB expression and therefore may be an important participant in the effect of morphine on immune responses in the central nervous system. © 2003 Wiley‐Liss, Inc.
Regulation of a Ca2+‐activated K+ channel by calcium‐sensing receptor involves p38 MAP kinase
Authors: Ye Chian Ping , Yano Shozo , Tfelt‐Hansen Jacob , MacLeod R. John , Ren Xianghui , Terwilliger Ernest , Brown Edward M. , Chattopadhyay Naibedya
Published: January 2004

By using pharmacological and molecular approaches, we previously showed that the G‐protein‐coupled, extracellular calcium (Ca)‐sensing receptor (CaR) regulates a large‐conductance (∼140 pS), Ca2+‐activated K+ channel [IK(Ca); CAKC] in U87 astrocytoma cells. Here we show that elevated Ca stimulates extracellular‐signal‐regulated kinase (ERK1/2) and p38 MAP kinase (MAPK). The effect of high Ca on p38 MAPK but not ERK1/2 is CaR mediated, insofar as transduction with a dominant‐negative CaR (R185Q) using recombinant adeno‐associated virus (rAAV) attenuated the activation of p38 MAPK but not of ERK1/2. p38 MAPK activation by the CaR is likely to be protein kinase C (PKC) independent, in that the pan‐PKC inhibitor GF109203X failed to abolish the high‐Ca‐induced phosphorylation of p38 MAPK. Consistently with our data on the activation of this kinase, we observed that inhibiting p38 MAPK blocked the activation of the CAKC induced by the specific pharmacological CaR activator NPS R‐467. In contrast, inhibiting MEK1 only transiently inhibited the activation of this K+ channel by NPS R‐467, despite the continued presence of the antagonist. Similarly to the lack of any effect of the PKC inhibitor on the activation of ERK1/2 and p38 MAPK, inhibiting PKC had no effect on NPS R‐467‐induced activation of this channel. Therefore, our data show that the CaR, acting via p38 MAPK, regulates a large‐conductance CAKC in U87 cells, a process that is PKC independent. Large‐conductance CAKCs play an important role in the regulation of cellular volume, so our results have important implications for glioma cell volume regulation. © 2004 Wiley‐Liss, Inc.
Anti‐Aβ: The good, the bad, and the unforeseen
Authors: Broytman Oleg , Malter James S.
Published: January 2004

Alzheimer's disease (AD) is characterized in part by the deposition of amyloid β protein (Aβ) in compact fibrillar plaques. These structures can induce an innate immune response in the brain, which triggers progressive inflammation, neuronal loss, and further acceleration of Aβ plaque formation. Compared with the case in normal individuals, the T and B lymphocytes in AD patients and murine models are hyporesponsive to Aβ. However, depending on the route of delivery, tolerance can be overcome by vaccination, with the induction of an anti‐Aβ‐mediated immune response. Through mechanisms that are incompletely understood, immunized APP transgenic animals show markedly reduced Aβ deposition, preservation of normal neuronal architecture, and improved performance in memory and spatial learning tasks. In human trials, Aβ vaccination stabilized cognition and slowed the progression of dementia. Neuropathologic examination of a vaccinated subject showed reduced cortical Aβ without changes in other AD‐associated pathology. However, in some patients, vaccination induced severe meningoencephalitis, causing the trial to be terminated. Thus, vaccination appears to activate both beneficial and deleterious anti‐Aβ immunity, suggesting that the vaccine can have potent clinical utility if an appropriate immunologic response can be generated. © 2003 Wiley‐Liss, Inc.
TNFα increases activity of γ‐glutamyl transpeptidase in cultured rat astroglial cells
Authors: Ruedig Cornelia , Dringen Ralf
Published: January 2004

To investigate the presence of γ‐glutamyl transpeptidase (γGT) in brain cells, cultures enriched for astroglial cells, neurons, oligodendroglial cells, and microglial cells were studied. Astroglial cultures contained a specific γGT activity of 2.3 ± 0.9 nmol/min/mg protein. A similar specific γGT activity was measured for oligodendroglial cultures, whereas microglial cells and neurons contained less than 30% of the specific γGT activity of astroglial cultures. The activity of γGT in astroglial cultures was elevated strongly by the presence of tumor necrosis factor‐α (TNFα) in a time‐ and concentration‐dependent manner. Maximal activity of γGT was observed after incubation of astroglial cultures for 3 days with 30 ng/mL TNFα. Under these conditions the specific γGT activity was increased by threefold compared to controls. Presence of the γGT‐inhibitor acivicin completely inhibited γGT activity both in TNFα‐treated and in control cells. In addition, the increase in astroglial γGT activity after application of TNFα was prevented completely by the presence of the protein synthesis inhibitor cycloheximide. γGT is involved in extracellular processing of glutathione (GSH) that is exported by astroglial cells. After TNFα‐treatment the concentration of GSH in the medium of astroglial cells was reduced significantly compared to control cells. In conclusion, the data presented demonstrate that TNFα stimulates γGT synthesis in astroglial cells and thereby improves the capacity to process GSH exported by these cells. © 2003 Wiley‐Liss, Inc.
Identification of a protein that interacts with the golli‐myelin basic protein and with nuclear LIM interactor in the nervous system
Authors: Fernandes Augustine O. , Campagnoni Celia W. , Kampf Kathy , Feng Ji‐Ming , Handley Vance W. , Schonmann Vilma , Bongarzone Ernesto R. , Reyes Sam , Campagnoni Anthony T.
Published: January 2004

The myelin basic protein (MBP) gene encodes the classic MBPs and the golli proteins, which are related structurally to the MBPs but are not components of the myelin sheath. A yeast two‐hybrid approach was used to identify molecular partners that interact with the golli proteins. A mouse cDNA was cloned that encoded a protein of 261 amino acids and called golli‐interacting protein (GIP). Database analysis revealed that GIP was the murine homolog of human nuclear LIM interactor‐interacting factor (NLI‐IF), a nuclear protein whose function is just beginning to be understood. It is a member of a broad family of molecules, found in species ranging from yeast to human, that contain a common domain of ∼100 amino acids. Immunocytochemical and Northern blot analyses showed co‐expression of GIP and golli in several neural cell lines. GIP and golli also showed a similar developmental pattern of mRNA expression in brain, and immunohistochemical staining of GIP and golli showed co‐expression in several neuronal populations and in oligodendrocytes in the mouse brain. GIP was localized predominantly in nuclei. GIP co‐immunoprecipitated with golli in several in vitro assays as well as from PC12 cells under physiologic conditions. GIP was the first member of this family shown to interact with nuclear LIM interactor (NLI). NLI co‐immunoprecipitated with GIP and golli from lysates of N19 cells transfected with NLI, further confirming an interaction between golli, GIP, and NLI. The ability of GIP to interact with both golli and NLI, and the nuclear co‐localization of GIP and golli in many cells, indicates a role for the golli products of the MBP gene in NLI‐ associated regulation of gene expression. © 2003 Wiley‐Liss, Inc.
CD4 T‐cell epitopes of human α B‐crystallin
Authors: Chou Yuan K. , Burrows Gregory G. , LaTocha Dorian , Wang Chunhe , Subramanian Sandhya , Bourdette Dennis N. , Vandenbark Arthur A.
Published: January 2004

Of potential importance to multiple sclerosis (MS), oligodendroglial α B‐crystallin is expressed and associated with the myelin sheath at the earliest stage of MS lesion development. We selected T‐cell lines specific for human α B‐crystallin from peripheral blood mononuclear cells (PBMC) of HLA‐DR2 homozygous MS patients and found that the α B‐crystallin‐specific T‐cells were CD4+ and restricted by DRB1*1501, and expressed Th1 cytokines. The CD4 T‐cell epitopes of human α B‐crystallin were determined by proliferation of α B‐crystallin‐specific T‐cell lines to 17 20‐mer synthetic overlapping peptides spanning the entire molecule of human α B‐crystallin. It was found that the HLA‐DR2 donor‐derived α B‐crystallin‐specific T‐cell lines proliferated to α B‐crystallin peptides 21–40, 41–60, and to a lesser extent, 131–150. These T‐cell proliferation responses were associated with intracellular expression of interleukin‐2 (IL‐2) and secretion of interferon‐γ (IFN‐γ), and tumor necrosis factor‐α (TNF‐α). The amino acid sequences of these peptides were compatible with predicted HLA‐DR2‐restricted binding motifs. PBMC of an early active MS patient proliferated to the epitope‐containing peptides significantly better than did those of later stage MS patients or healthy controls. Taken together, these findings suggest that autoreactive α B‐crystallin‐specific Th1 cells may have the potential to contribute to MS pathogenesis. © 2004 Wiley‐Liss, Inc.
Enhanced inflammatory response in neural tubes of embryos derived from diabetic mice exposed to a teratogen
Authors: Lian Qizhou , Dheen S. Thameem , Liao Dongmei , Tay Samuel Sam Wah
Published: January 2004

Exposure of embryos to the teratogen cyclophosphamide (CP) and maternal diabetes is linked to pathogenesis of neural tube defects during development. Maternal diabetes aggravates the teratogen‐induced inflammatory reaction leading to increased risk of neural tube defects in mouse embryos. The inflammatory reaction in the developing neural tube has been characterized by the presence of activated amoeboid microglia/brain macrophages and altered expression levels of cytokines. Although there were no obvious anomalies observed in the neural tubes of embryos from CP‐treated non‐diabetic mice, the frequency of neural tube defects was increased significantly in embryos of CP‐treated diabetic mice. Moreover, there were more activated amoeboid microglia in the forebrain of CP‐treated diabetic embryos compared to that in CP‐treated non‐diabetic mice. The expression of cytokines such as tumor necrosis factor‐α (TNF‐α) and transforming growth factor‐β1 (TGF‐β1) in the fetal brain of normal and diabetic embryos was induced in the neural tubes after CP treatment. Furthermore, the mRNA expression levels of both genes were increased markedly in the neural tube of CP‐treated diabetic embryos compared to that of CP‐treated non‐diabetic embryos as measured by quantitative real‐time PCR. Immunohistochemically, more TNF‐α‐ and TGF‐β1‐positive cells, which included neurons and amoeboid microglia, were detected in CP‐treated diabetic embryos than in CP‐treated normal embryos. Maternal diabetes aggravates teratogen‐induced inflammation, which is characterized in the developing neural tube by increased amoeboid microglia and enhanced expression of inflammatory cytokines. Although a definite link has yet to be elucidated, it is suggested that the increased rate of neural tube defects observed in CP‐treated diabetic embryos may be due to upregulation of proinflammatory cytokines caused by maternal diabetes. © 2004 Wiley‐Liss, Inc.
Differential subcellular distribution of Ca2+/calmodulin‐dependent protein kinase II isoforms in the striatum and NG108‐15 cells
Authors: Takeuchi Yusuke , Nomura Kazumi , Fukunaga Kohji
Published: January 2004

Four subunits of Ca2+/calmodulin‐dependent protein kinase II (CaM KII) have several isoforms, which differ in the variable domain. We previously reported that all subunits were highly expressed in rat striatal neurons. To examine intracellular distributions of CaM KII subunits in the rat striatal neurons, we performed immunoblot analysis with antibodies specific to each subunit in cell extracts from the rat striatum after continuous sucrose density gradient fractionation. The α subunit, but not the β, γ, or δ subunits, was colocalized with synapsin I, and each subunit showed a distinct distribution pattern in the fractions. To examine further the intracellular distributions of CaM KII isoforms in the same subunit, we established NG108‐15 cells stably expressing δ1, δ3, and δ4 isoforms and examined distributions of the δ and γ isoforms in these cell lines after fractionation. Each of the overexpressed exogenous δ isoforms showed a distinct distribution pattern. The endogenous δ2 was colocalized with the overexpressed δ1, δ3, and δ4 isoforms. However, the endogenous γB/γC isoforms were not colocalized with the overexpressed δ isoforms. Furthermore, the endogenous δ1 was concentrated in the microsomal fraction from the rat striatum. With the results taken together, it is suggested that CaM KII forms oligomers between isoforms in the same subunit but not in different subunits. The variable domain of CaM KII isoforms might possibly be responsible for targeting to certain intracellular compartments. © 2004 Wiley‐Liss, Inc.
Noise trauma alters D‐[3H]aspartate release and AMPA binding in chinchilla cochlear nucleus
Authors: Muly S.M. , Gross J.S. , Potashner S.J.
Published: January 2004

Exposure of adults to loud noise can overstimulate the auditory system, damage the cochlea, and destroy cochlear nerve axons and their synaptic endings in the brain. Cochlear nerve loss probably results from the death of cochlear inner hair cells (IHC). Additional degeneration in the cochlear nucleus (CN) is hypothesized to stem from overstimulation of the system, which may produce excitotoxicity. This study tested these predictions by exposing one ear of anesthetized adult chinchillas to a loud noise, which damaged the ipsilateral cochlea and induced degeneration in the glutamatergic cochlear nerve. During the first postexposure week, before cochlear nerve axons degenerated, glutamatergic synaptic release in the ipsilateral CN was elevated and uptake was depressed, consistent with hyperactivity of glutamatergic transmission and perhaps with the operation of an excitotoxic mechanism. By 14 days, when cochlear nerve fibers degenerated, glutamatergic synaptic release and uptake in the CN became deficient. By 90 days, a resurgence of transmitter release and an elevation of AMPA receptor binding suggested transmission upregulation through plasticity that resembled changes after mechanical cochlear damage. These changes may contribute to tinnitus and other pathologic symptoms that precede and accompany hearing loss. In contrast, the other ear, protected with a silicone plug during the noise exposure, exhibited virtually no damage in the cochlea or the cochlear nerve. Altered glutamatergic release and AMPA receptor binding activity in the CN suggested upregulatory plasticity driven by signals emanating from the CN on the noise‐exposed side. © 2004 Wiley‐Liss, Inc.
Circulation weather types and cloud‐to‐ground flash density over the Iberian Peninsula
Authors: Tomás Clemente , de Pablo Fernando , Rivas Soriano Luis
Published: January 2004

Based on the use of an objective classification method for the general atmospheric circulation observed over the Iberian Peninsula for the 1990–98 period, we have characterized the daily circulation by means of a set of indices associated with the direction and vorticity of the geostrophic flow.

We analyse the synoptic characteristics of the types of circulation obtained, gaining statistical information about the most frequent basic situations for the annual and seasonal periods. We show how the anticyclone situation (A) predominates in winter, spring and autumn, whereas in summer the most frequent weather corresponds to pure easterly weather (E) followed by cyclonic weather (C).

We report the findings of a comparative study between the frequencies of the daily values of the dominant types of circulation and the corresponding daily values of the number of cloud‐to‐ground flashes over the Iberian Peninsula between 1992 and 1994. Each synoptic situation is described by a set of characteristics that explains the development of the convective processes. A high degree of correspondence was obtained, especially for the months between May and October, in which major storm activity occurs (Pearson correlation coefficient: 0.76). All the results show that convective processes, which generate storm activity, can be appropriately explained in terms of the variability of a small number of general synoptic situations. Copyright © 2004 Royal Meteorological Society
The surface wind field during winter smog nights in Christchurch and coastal Canterbury, New Zealand
Authors: Kossmann Meinolf , Sturman Andrew
Published: January 2004

In Christchurch and other Canterbury towns on the east coast of New Zealand's South Island, poor dispersion conditions and high emissions of particulate matter and carbon monoxide regularly lead to the build‐up of smog during anticyclonic weather conditions in wintertime. This study analyses surface wind fields during smog nights using data collected during the Christchurch Air Pollution Study 2000 (CAPS2000). Westerly land breezes and drainage winds from the foothills of the Southern Alps and the Canterbury Plains are evident in all coastal Canterbury towns, but local terrain features often complicate the wind fields. This holds particularly for Christchurch, where Banks Peninsula causes flow splitting of both the drainage winds on the Canterbury Plains and any superimposed larger scale winds. Furthermore, stagnation of airflow over Christchurch is often caused by the convergence of localized southeasterly drainage winds down the western part of the Banks Peninsula (Port Hills) with the regional‐scale northwesterly drainage winds from the Canterbury Plains. Results illustrate the interaction of cold air drainage over Christchurch, although the unusually high frequency of synoptic‐scale easterly winds during the study period appeared to reduce the effects of both these sources of cold air drainage on air pollution concentrations. The effects of topographically induced flow splitting and non‐stationary drainage wind convergence on urban air pollution dispersion identified here have not previously been studied in detail internationally and should receive greater attention in the future. Copyright © 2004 Royal Meteorological Society
Over one century of rainfall and temperature observations in Addis Ababa, Ethiopia
Authors: Conway Declan , Mould Colin , Bewket Woldeamlak
Published: January 2004

A detailed historical reconstruction and analysis is presented of the longest record of climate observations for Ethiopia, from 1898 to 2002 in Addis Ababa. Prior to 1951 the record comprises rainfall and minimum and maximum temperatures recorded in different locations by different observers. The rainfall series is complete except for 1899 and 1900, but the temperature series are very incomplete. Using documentary evidence, we attempt as far as is possible to establish the origins of all the pre‐1951 observations. Rainfall observations originate from at least six different sites. After establishment of an Ethiopian meteorological department in 1951 the records are complete and, to our understanding, originate from the same location, the Addis Ababa Observatory (AAO). A revised rainfall series for 1898–1950 is derived using observations from sites with the longest records.

The minimum and maximum temperature records show evidence of statistically significant inhomogeneities. Homogeneity tests on the full rainfall record (the revised series plus AAO) show it is reliable, with evidence of minor but not statistically significant breaks in the record before establishment of the AAO. Some, but not all, breaks can be accounted for using the historical information. Analysis of the records shows increasing trends in annual minimum and maximum temperatures from 1951 to 2002 (0.4 °C/decade and 0.2 °C/decade, respectively). There is little trend in rainfall from 1901–50, 1951–2002 and 1901–2002, dry years do not correspond with known drought years elsewhere in Ethiopia, and interannual variability is poorly correlated with another long rainfall series in Ethiopia (Gore), Blue Nile river flows and the southern oscillation index. This suggests strongly that the record for Addis Ababa should not be used as a proxy for conditions in Ethiopia, particularly the more drought‐prone areas to the north and east. We conclude that the temperature series are suspect but that the full rainfall record is useful for analysis of long‐term rainfall conditions in Addis Ababa. Copyright © 2004 Royal Meteorological Society