bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence for a Lactate Pool in the Rat Brain That is Not Used as an Energy Supply under Normoglycemic Conditions
Authors: Leegsma-Vogt Gea , Venema Kor , Korf Jakob
Published: November 2003

Lactate derived from glucose can serve as an energy source in the brain. However, it is not certain how much lactate, directly taken from the blood circulation, may replace glucose as an energy source. This study aimed to estimate the uptake, release, and utilization of lactate entering the brain from the blood circulation. The change in cerebral venous-arterial glucose and lactate differences after lactate infusions in the anesthetized rat were measured. Ultrafiltration probes were placed in the aorta and in the jugular vein, and connected to a flow injection analysis system with biosensors for glucose and lactate. Measurements were taken every minute. Lactate efflux was observed at baseline, whereas an influx of lactate was seen during lactate infusion. Immediately after the infusion there was a net efflux of lactate from the brain. The results suggest that the majority of lactate moving into the brain is not used as an energy substrate, and that lactate does not replace glucose as an energy source. Instead, the authors propose the concept of a lactate pool in the brain that can be filled and emptied in accordance with the blood lactate concentration, but which is not used as an energy supply for cerebral metabolism.
Interferon-Beta Prevents Cytokine-Induced Neutrophil Infiltration and Attenuates Blood–Brain Barrier Disruption
Authors: Veldhuis Wouter B. , Floris Sarah , van der Meide Peter H. , Vos Ine M. P. , de Vries Helga E. , Dijkstra Christien D. , Bär Peter R. , Nicolay Klaas
Published: November 2003

Inflammation can contribute to brain injury, such as that resulting from ischemia or trauma. The authors have previously shown that the cytokine interferon-beta (IFN-β) affords protection against ischemic brain injury, which was associated with a diminished infiltration of neutrophils and a reduction in blood–brain barrier (BBB) disruption. The goal of the current study was to directly assess the effects of IFN-β on neutrophil infiltration, with the use of an in vivo assay of neutrophil infiltration with relevance to ischemic brain injury. Intrastriatal injection of recombinant rat cytokine–induced neutrophil chemoattractant-1, a member of the interleukin-8 family (1 μg in 1 μL), triggered massive infiltration of neutrophils and extensive BBB disruption 6 hours later, as measured using immunofluorescence microscopy and magnetic resonance imaging in the rat, respectively. Depleting the animals of neutrophils before interleukin-8 injection prevented BBB disruption. Treatment with IFN-β (5 × 106 U/kg) almost completely prevented neutrophil infiltration and attenuated BBB damage. Gelatinase zymography showed matrix metalloproteinase-9 expression in the ipsilateral striatum after interleukin-8 injection. Both neutrophil depletion and IFN-β treatment downregulated matrix metalloproteinase-9. IFN-β has already been approved for human use as a treatment for the chronic inflammatory disorder multiple sclerosis. The potential value of IFN-β as a treatment that can attenuate acute brain inflammation is considered.
Interaction between XIAP and Smac/DIABLO in the Mouse Brain after Transient Focal Cerebral Ischemia
Authors: Saito Atsushi , Hayashi Takeshi , Okuno Shuzo , Ferrand-Drake Michel , Chan Pak H.
Published: November 2003

The X chromosome–linked inhibitor-of-apoptosis protein (XIAP) contributes to apoptosis regulation after a variety of cell death stimuli. XIAP inhibits the caspase reaction via binding to caspases, and is inhibited via binding to the second mitochondria-derived activator of caspase (Smac)/DIABLO to tightly control apoptotic cell death. However, the interaction among XIAP, Smac/DIABLO, and caspases after in vivo cerebral ischemia is not well known. To clarify this issue, the authors examined time-dependent expression and interaction among XIAP, Smac/DIABLO, and activated caspase-9 by immunohistochemistry, Western blot analysis, and immunoprecipitation using an in vivo transient focal cerebral ischemia model. To examine the relationship of the XIAP pathway to the caspase cascade, a pan-caspase inhibitor was administered. XIAP increased concurrently with the release of Smac/DIABLO and the appearance of activated caspase-9 during the early period after reperfusion injury. The bindings of XIAP to Smac/DIABLO and to caspase-9 and the binding of Smac/DIABLO to caspase-9 reached a peak simultaneously after transient focal cerebral ischemia. Neither XIAP nor Smac/DIABLO expression was affected by caspase inhibition. These results suggest that the XIAP pathway was activated upstream of the caspase cascade and that interaction among XIAP, Smac/DIABLO, and caspase-9 plays an important role in the regulation of apoptotic neuronal cell death after transient focal cerebral ischemia.
Energy Substrates for Neurons during Neural Activity: A Critical Review of the Astrocyte-Neuron Lactate Shuttle Hypothesis
Authors: Chih Ching-Ping , Roberts Eugene L
Published: November 2003

Glucose had long been thought to fuel oxidative metabolism in active neurons until the recently proposed astrocyte-neuron lactate shuttle hypothesis (ANLSH) challenged this view. According to the ANLSH, activity-induced uptake of glucose takes place predominantly in astrocytes, which metabolize glucose anaerobically. Lactate produced from anaerobic glycolysis in astrocytes is then released from astrocytes and provides the primary metabolic fuel for neurons. The conventional hypothesis asserts that glucose is the primary substrate for both neurons and astrocytes during neural activity and that lactate produced during activity is removed mainly after neural activity. The conventional hypothesis does not assign any particular fraction of glucose metabolism to the aerobic or anaerobic pathways. In this review, the authors discuss the theoretical background and critically review the experimental evidence regarding these two hypotheses. The authors conclude that the experimental evidence for the ANLSH is weak, and that existing evidence and theoretical considerations support the conventional hypothesis.
Absence of the Transcription Factor E2F1 Attenuates Brain Injury and Improves Behavior after Focal Ischemia in Mice
Authors: MacManus John P. , Jian Ming , Preston Edward , Rasquinha Ingrid , Webster Jackie , Zurakowski Bogdan
Published: November 2003

Because of observations that cultured neurons from mice deficient in the transcription factor E2F1 exhibit resistance after treatment with a wide variety of cell-death inducers, the authors investigated whether resistance extended to a cerebral ischemic insult. No differences in cerebral blood flow or physiologic parameters were observed in the mutant E2F1 littermates after the focal ligation. After 2 hours of left middle cerebral artery occlusion and 1 day of reperfusion, a 33% smaller infarct ( P < 0.05) was observed by 2,3,5-triphenyltetrazolium staining in the brains of E2F1-null mice compared with their E2F1+/+ and +/− littermates. A milder ischemic insult produced by 20 minutes of middle cerebral artery occlusion and 7 days of reperfusion produced a greater difference in the E2F1-null animals with a 71% smaller infarct ( P < 0.001) compared to littermate controls. A decrease in neuronal damage after mild ischemia in E2F1-null mice was observed by immunohistochemical monitoring of the loss in neuronal-specific microtubule-associated protein 2 cytoskeletal protein and the appearance of nuclear DNA fragmentation by terminal deoxynucleotidyl transferase-mediated 2′-deoxyuridine 5′-triphosphate-biotin nick end labeling. This decreased brain damage was evidenced by improved behavior in motor function of E2F1 −/− mice compared with their E2F1 +/+ littermates by 7 days of reperfusion. In an effort to address the underlying molecular mechanism of the resistance of E2F1-null mice, the expression of several downstream proapoptotic target genes ( p73, Apaf1, Arf) of the E2F1 transcription factor was measured by quantitative polymerase chain reaction. Although an attenuated increase in Hsp68 mRNA was found in E2F1 −/− mice, no changes in the proapoptotic transcripts were found after ischemia, and a mechanistic inference was not possible. The authors conclude that the transcription factor E2F1 does modulate neuronal viability in brain after cerebral ischemia and corroborates the findings with cultured neurons.
Monoubiquitination and Cellular Distribution of XIAP in Neurons after Traumatic Brain Injury
Authors: Lotocki George , Alonso Ofelia F , Frydel Beata , Dietrich W Dalton , Keane Robert W
Published: November 2003

XIAP is a member of the inhibitor of apoptosis (IAP) gene family that, in addition to suppressing cell death by inhibition and polyubiquitination of caspases, is involved in an increasing number of signaling cascades. Moreover, the function and regulation of XIAP in the central nervous system (CNS) is poorly understood. In this study, the authors investigated the cell-type expression, the subcellular distribution, ubiquitination of XIAP, and levels of Smac/DIABLO in the normal adult rat brain and in brains subjected to moderate traumatic brain injury (TBI). In the normal brain, XIAP was predominantly expressed in the perinuclear region of neurons. Traumatized brains showed dramatic alterations in cellular and regional expression of XIAP early after injury. Stereologic analyses of the number of XIAP-positive cells within the hippocampus of both hemispheres showed a biphasic response. Immunoprecipitation and immunoblots of extracts derived from different brain regions demonstrated that a single ubiquitin modifies XIAP. Normal cortex contained significantly higher levels of monoubiquitinated XIAP than hippocampus. TBI induced alterations in levels of monoubiquitinated XIAP that correlated with changes in XIAP distribution and immunoreactivity, suggesting that monoubiquitination of XIAP may be a regulator of XIAP location or activity. Similar levels of Smac/DIABLO were present in lysates of normal and traumatized brains. These data demonstrate for the first time a region-specific regulation of XIAP monoubiquitination in the normal adult rat brain, and after TBI, that may be a key event in the regulation of XIAP function contributing to the pathogenesis following injury.
Translocation of Apoptosis-Inducing Factor in Vulnerable Neurons after Transient Cerebral Ischemia and in Neuronal Cultures after Oxygen-Glucose Deprivation
Authors: Cao Guodong , Clark Robert S B , Pei Wei , Yin Wei , Zhang Feng , Sun Feng-Yan , Graham Steven H , Chen Jun
Published: November 2003

Loss of mitochondrial membrane integrity and the resulting release of apoptogenic factors may play a critical role in mediating hippocampal neurodegeneration after transient global ischemia. In the present study, the authors have cloned and characterized the rat cDNA encoding apoptosis-inducing factor (AIF), an intramitochondrial protein that promotes cell death in a caspase-independent manner upon release into nonmitochondrial compartments. In contrast to the expression patterns of a number of apoptosis-regulatory gene products during brain development, the expression of AIF protein increases gradually with brain maturation and peaks in adulthood. In a rat model of transient global ischemia, AIF was found to translocate from mitochondria to the nucleus in the hippocampal CA1 neurons after ischemia and to manifest a DNA-degrading activity that mimicked the purified AIF protein and was inhibitable by AIF immunodepletion. The temporal profile of AIF translocation after ischemia (24 to 72 hours) coincided with the induction of large-scale DNA fragmentation at the size of 50 kbp, a well-characterized hallmark of AIF-like activity but preceded the formation of internucleosomal DNA fragmentation (72 hours), a DNA degradation associated with the terminal stage of cell death. Further, the nuclear translocation of AIF after ischemia was not blocked by inhibiting caspase-3/-7 activities, but, as shown in neuronal cultures that were challenged with transient oxygen-glucose deprivation, it can be prevented by intracellular delivery of the mitochondria-associated antiapoptotic protein Bcl-xL. The results presented here strongly suggest that mitochondrial release of AIF may be an important factor, in addition to the previously reported cytochrome c and Smac, which could contribute to the selective vulnerability of CA1 neurons to transient global ischemic injury.
Differential Effects of Atrial Natriuretic Peptide on the Brain Water and Sodium after Experimental Cortical Contusion in the Rat
Authors: Fukui Shinji , Fazzina Giovanna , Amorini Angela M , Dunbar Jana G , Marmarou Anthony
Published: November 2003

Atrial natriuretic peptide (ANP) plays an important role in the regulation of water and sodium in the body via cyclic GMP (cGMP) pathway. Although ANP has been shown to be protective in cerebral ischemia or intracerebral hemorrhage, its role in traumatic brain injury (TBI) has yet to be elucidated. We herein assessed ANP effects on brain water and sodium in TBI. Controlled cortical impact (3 mm depth, 6 m/sec) was used to induce an experimental cortical contusion in rats. Continuous administration of ANP 0.2 (n = 6) or 0.7 μg/kg/24 h (n = 6), cGMP analogue (8-Bromo-cGMP) 0.1 (n = 5) or 0.3 mg/kg/24 h (n = 5), or vehicle (n = 6) was begun 15 minutes after injury, using a mini-osmotic pump implanted into the peritoneal cavity. At 24 hours after injury, ANP significantly exacerbated brain edema in the injured hemisphere in a dose-dependent manner while it reduced brain sodium concentrations in both hemispheres. These ANP effects could be mimicked by a cGMP analogue. In the second series (n = 20), BBB integrity was assessed by evaluating the extravasation of Evans blue dye. ANP or cGMP analogue significantly worsened BBB disruption in the injured hemisphere at 24 hours after injury. These findings suggest that ANP administration exacerbates brain edema after the experimental cortical contusion in rats, possibly because of an increase in the BBB permeability via cGMP pathway, whereas it reduces brain sodium levels.
DNA Microarray Analysis of Hippocampal Gene Expression Measured Twelve Hours after Hypoxia-Ischemia in the Mouse
Authors: Gilbert Robert W , Costain Willard J , Blanchard Marie-Eve , Mullen Kerry L , Currie R William , Robertson Harold A
Published: November 2003

Cell death from cerebral ischemia is a dynamic process. In the minutes to days after an ischemic insult, progressive changes in cellular morphology occur. Associated with these events is the regulation of competing programs of gene expression; some are protective against ischemic insult, and others contribute to delayed cell death. Many genes involved in these processes have been identified, but individually, these findings have provided only limited insight into the systems biology of cerebral ischemia. Attempts to characterize the coordinated expression of large numbers of genes in cerebral ischemia has only recently become possible. Today, DNA microarray technology provides a powerful tool for investigating parallel expression changes for thousands of genes at one time. In this study, adult mice were subjected to 30 minutes of hypoxia-ischemia (HI), and the hippocampus was examined 12 hours later for differential gene expression using a 15K high-density mouse EST array. The genomic response to HI is complex, affecting approximately 7% of the total number of ESTs examined. Assigning differentially expressed ESTs to molecular functional groups revealed that HI affects many pathways including the molecular chaperones, transcription factors, kinases, and calcium ion binding genes. A comprehensive list of regulated genes should prove valuable in advancing our understanding of the pathogenesis of cerebral ischemia.
Contributions of Endothelial and Neuronal Nitric Oxide Synthases to Cerebrovascular Responses to Hyperoxia
Authors: Atochin D N , Demchenko I T , Astern J , Boso A E , Piantadosi C A , Huang P L
Published: November 2003

Hyperoxia causes a transient decrease in CBF, followed by a later rise. The mediators of these effects are not known. We used mice lacking endothelial or neuronal nitric oxide synthase (NOS) isoforms (eNOS−/− and nNOS−/− mice) to study the roles of the NOS isoforms in mediating changes in cerebral vascular tone in response to hyperoxia. Resting regional cerebral blood flow (rCBF) did not differ between wild type (WT), eNOS−/− mice, and nNOS−/− mice. eNOS−/− mice showed decreased cerebrovascular reactivities to NG-nitro-L-arginine methyl ester (L-NAME), PAPA NONOate, acetylcholine (Ach), and SOD1. In response to hyperbaric oxygen (HBO2) at 5 ATA, WT and nNOS−/− mice showed decreases in rCBF over 30 minutes, but eNOS−/− mice did not. After 60 minutes HBO2, rCBF increased more in WT mice than in eNOS−/− or nNOS−/− mice. Brain NO-metabolites (NOx) decreased in WT and eNOS−/− mice within 30 minutes of HBO2, but after 45 minutes, NOx rose above control levels, whereas they did not change in nNOS−/− mice. Brain 3NT increased during HBO2 in WT and eNOS−/− but did not change in nNOS−/− mice. These results suggest that modulation of eNOS-derived NO by HBO2 is responsible for the early vasoconstriction responses, whereas late HBO2-induced vasodilation depends upon both eNOS and nNOS.
in Vivo Monitoring of Macrophage Infiltration in Experimental Ischemic Brain Lesions by Magnetic Resonance Imaging
Authors: Kleinschnitz Christoph , Bendszus Martin , Frank Marco , Solymosi Laszlo , Toyka Klaus V , Stoll Guido
Published: November 2003

Although macrophages represent the major inflammatory cells in cerebral ischemia, the kinetics of macrophage infiltration are largely unknown. To address this issue, we injected superparamagnetic iron oxide (SPIO) particles into the circulation of rats at different time points after focal photothrombotic cerebral infarction and performed magnetic resonance imaging (MRI) 24 hours later. Infarcts appeared as hyperintense lesions on T2-w and CISS MR images during all stages. At days 5.5 and 6, an additional rim of signal loss indicative of local accumulation of SPIO particles appeared at the outer margin of the hyperintense ischemic lesions, which was not present at days 1 to 5. Areas of signal loss corresponded to local accumulation of iron-loaded macrophages in histologic sections. At day 8, signal loss became restricted to the inner core of the lesions and ceased thereafter. Macrophages, however, were still present in late ischemic brain lesions, but they were iron-negative. Thus SPIO-induced signal loss indicates active macrophage transmigration into ischemic infarcts but not their mere presence. SPIO-induced signal loss was independent from the disturbance of the blood-brain barrier. In conclusion, we have shown by in vivo monitoring that macrophages enter photothrombotic infarcts at late stages of infarct development, suggesting a role in tissue remodeling rather than neuronal injury.
Putative Cyclooxygenase-3 Expression in Rat Brain Cells
Authors: Kis Bela , Snipes James A , Isse Toyohi , Nagy Krisztina , Busija David W
Published: November 2003

Cyclooxygenase-3 (COX-3), a new acetaminophen-sensitive isoform of the COX family, has recently been cloned from canine tissues. Canine COX-3 apparently is identical to the full-length form of COX-1, with the exception that the COX-3 mRNA retains intron 1. Additionally, COX-3 mRNA expression is high in the brain. We investigated the expression of the putative rat COX-3 mRNA in primary cultures of neurons, astrocytes, endothelial cells, pericytes, and choroidal epithelial cells from the rat brain. Specific RT-PCR primers were designed to detect putative rat COX-3 mRNA, and the RT-PCR products were sequenced and compared to the known sequence of the rat COX-1 gene. Our results demonstrate that the mRNA of the putative COX-3 is expressed in all of the cell types except neurons. Cerebral endothelial cells showed the highest COX-3 expression. Whereas COX-2 expression increased several-fold after lipopolysaccharide (LPS) challenge, COX-1 and COX-3 expression did not change significantly, suggesting that cells constitutively express COX-3. In summary, we report, for the first time to our knowledge, that the putative COX-3 mRNA is detectable in rats and is differentially expressed in various cell types from rat brain, as well as that its expression is not stimulated by LPS.
Microvascular Basal Lamina Damage after Embolic Stroke in the Rat: Relationship to Cerebral Blood Flow
Authors: Hamann Gerhard F , Schröck Helmut , Burggraf Dorothe , Wunderlich Nathalie , Liebetrau Martin , Kuschinsky Wolfgang
Published: November 2003

Microvascular basal lamina damage has been demonstrated after balloon occlusion of the middle cerebral artery in the nonhuman primate and after intravascular filament occlusion in the rat. The aim of the present study was to investigate in the rat whether microvascular damage can be found in the stroke model of intracarotid clot injection as early as 3 hours after clot injection and whether microvascular damage relates to the level of regional cerebral blood flow (rCBF). Microvascular densities and total stained microvascular areas were determined by immunohistochemistry of collagen type IV in cortex and basal ganglia and automatic video-imaging analysis. rCBF was measured by autoradiography in the same brain areas. Compared with the corresponding areas in the nonischemic hemisphere, a significant loss of microvascular density (−16%) and total stained microvascular areas (−10%) was observed in these areas. The reduction of microvascular basal lamina staining was comparable in all animals and was not related to the value of rCBF when measured 3 hours after onset of embolic stroke. In conclusion, microvascular damage occurs as soon as 3 hours after intracarotid clot injection, even in brain areas in which rCBF has returned to normal values.
Translational Paradigms in Cerebrovascular Gene Transfer
Authors: Khurana Vini G , Meyer Fredric B
Published: November 2003

Gene transfer involves the use of an engineered biologic vehicle known as a vector to introduce a gene encoding a protein of interest into a particular tissue. In diseases with known defects at a genetic level, gene transfer offers a potential means of restoring a normal molecular environment via vector-mediated entry (transduction) and expression of genes encoding potentially therapeutic proteins selectively in diseased tissues. The technology of gene transfer therefore underlies the concept of gene therapy and falls under the umbrella of the current genomics revolution. Particularly since 1995, numerous attempts have been made to introduce genes into intracranial blood vessels to demonstrate and characterize viable transduction. More recently, in attempting to translate cerebrovascular gene transfer technology closer to the clinical arena, successful transductions of normal human cerebral arteries ex vivo and diseased animal cerebral arteries in vivo have been reported using vasomodulatory vectors. Considering the emerging importance of gene-based strategies for the treatment of the spectrum of human disease, the goals of the present report are to overview the fundamentals of gene transfer and review experimental studies germane to the clinical translation of a technology that can facilitate genetic modification of cerebral blood vessels.
Comparison of structures between platinum and palladium complexes of a tetrasilyldisilene
Authors: Hashimoto Hisako , Sekiguchi Yumiko , Sekiguchi Yohei , Iwamoto Takeaki , Kabuto Chizuko , Kira Mistuo
Published: November 2003

The first η2-disilenepalladium complexes were synthesized using two different reactions; the reactions of bis(phosphine)dichloropalladiums with a 1,2-dilithiotetrakis(trialkylsilyl)disilane, which was prepared by the reaction of a stable tetrakis(trialkylsilyl)disilene with lithium (Method A) and the direct reactions of the bis(phosphine)dichloropalladiums with the stable disilene (Method B). Comparison of X-ray structural parameters of the disilenepalladium complexes with those of the corresponding platinum complex has indicated that the palladium complex is a metallacycle but its π-complex character is stronger than that of the platinum complex.Key words: disilene complex, palladium, platinum, X-ray structure, metallacycle, π-complex.
Structural elucidations of T8 and Q8 silsesquioxane cages containing two types of pendant group using 29Si NMR spectroscopy
Authors: Bassindale Alan Richard , Parker David John , Taylor Peter Geoffrey , Watt Alison Claire
Published: November 2003

The products from the reaction of octahydrosilsesquioxane (T8-H) with different molar ratios of phenol and undec-1-ene or methyl 3,3-dimethylpent-4-enoate (MDP) in the presence of chloroplatinic acid have been analysed by 29Si NMR spectroscopy. The distribution of the two different pendant groups leads to tetrad patterns where the relative chemical peak intensities reflect the selectivity for particular patterns of substitution. As well as analysing the cause of these tetrad patterns we also discuss how the regioselectivity of hydrosilylation can be determined.Key words: T8, Q8, silsesquioxane, 29Si NMR, hydrosilylation, tetrad pattern, regioselectivity, statistical modelling.
The activity of Pt/SiO2 catalysts obtained by the sol-gel method in the hydrosilylation of 1-alkynes
Authors: Jiménez Rafael , Martínez-Rosales J Merced , Cervantes Jorge
Published: November 2003

Heterogeneous platinum catalysts (Pt/SiO2) obtained by the sol-gel process at pH 3 and 9 have been used in the hydrosilylation reaction of 1-alkynes using various silanes. Once the catalysts were activated they were used in the hydrosilylation of 1-alkynes after a short induction period. The product distribution was quite similar in either case but important differences in catalytic activity and turnover reactions were observed. The catalyst obtained in the basic medium after each reaction lost its catalytic activity, so further activation was needed. To understand this behavior, the catalysts were characterized by 29Si CPMAS NMR, FT IR, and BET surface area measurements. The 29Si CPMAS NMR studies showed the presence of terminal and bridged hydroxyl groups in the Pt/SiO2 catalyst at pH = 9. Similar results were observed by FT IR analysis because of the catalysts' synthetic conditions.Key words: hydrosilylation, sol-gel, Pt/SiO2, supported-metal catalysts, phenylacetylene, diphenylacetylene, 29Si NMR CP-MAS.
Preparation and electronic properties of rhenium(V) complexes with bis(diphenyl phosphino)ethane
Authors: Baril-Robert François , Beauchamp André L
Published: November 2003

Complexes of bis(diphenylphosphino)ethane (dppe) of the types ReOX3(dppe) and ReO(OR)X2(dppe) (with X= Cl or Br, and R = Me, Et, Pr, Ph, cyclohexyl (Cy), or -CH2CH2OH) were prepared to evaluate the influence of ligand changes on the low-energy dd transitions in these Re(V) low-spin d2 systems. Arylimido compounds Re(NR)Cl3(dppe) (with R = Ph and p-ClC6H4) were also obtained. X-ray diffraction studies on ReO(OPr)Cl2(dppe), ReO(OPh)Br2(dppe), and ReO(OCy)Cl2(dppe) confirmed the presence of the trans O=Re-OR unit and showed that the structural characteristics of the Re-O-R segment are not affected by the presence of a bulky cyclohexyl substituent or an aromatic phenyl group. The structure of the arylimido complex Re(p-ClC6H4N)Cl3(dppe) was also determined. The electronic absorption spectra of the ReOX3(dppe) compounds include two low-energy components at ~11 500 and ~16 000 cm1, assigned to the two spin-allowed dd transitions expected for these low-symmetry systems. Substitution of the oxo ligand by an arylimido group has little effect on the lower-energy component, but moves the two components closer together. Replacing the halogen trans to the Re=O bond by an alkoxo group shifts the whole system to higher energies. These variations were found to correlate well with the energies of the frontier orbitals determined from DFT calculations. While attempting to prepare ReOCl3(dppe) from ReOCl3(PPh3)2, the Re(III) compound fac-ReCl3(PPh3){Ph2PC2H4PPh2(O)} was obtained, in which one end of dppe had become a phosphine oxide. Upon standing in DMSO, this compound gave the octahedral compound ReCl4{Ph2PC2H4PPh2(O)}, in which the formation of a chelate ring involving a phosphine and a phosphine oxide was ascertained by X-ray diffraction.Key words: rhenium, crystal structure, DFT calculations, dd electron transitions.
Synthesis, first structures, and catalytic activity of the monomeric rhodium(I)-siloxide phosphine complexes
Authors: Marciniec Bogdan , Błażejewska-Chadyniak Paulina , Kubicki Maciej
Published: November 2003

Four new square-plane rhodium siloxide complexes of the general formula [Rh(cod)(PR3′)(OSiR3)] (where R = Me, i-Pr, O-t-Bu, R′ = Cy, Ph) were synthesized and the structures of three of them were resolved by the X-ray method. [Rh(cod)(PCy3)(OSiMe3)] (1) appeared to be a very efficient catalyst for hydrosilylation of allyl glycidyl ether to yield, selectively, 3-glycidoxypropyltriethoxysilane, a commercially important silane coupling agent. Catalytic measurements and stoichiometric experiments of 1 with triethoxysilane suggest a mechanism where an unsaturated Rh-H species is responsible for the catalysis.Key words: rhodium (phosphine) siloxides, hydrosilylation, catalysis.
Overexpression of Decorin by Rat Arterial Smooth Muscle Cells Enhances Contraction of Type I Collagen In Vitro
Authors: Järveläinen Hannu , Vernon Robert B. , Gooden Michel D. , Francki Aleksandar , Lara Stephanie , Johnson Pamela Y. , Kinsella Michael G. , Sage E. Helene , Wight Thomas N.
Published: November 2003

Objective—

Overexpression of decorin reduces neointimal thickening in balloon-injured carotid arteries of rats by decreasing the volume of neointimal extracellular matrix (ECM). We examined the hypothesis that decorin regulates ECM volume by stimulating cell-mediated contraction of collagen-rich ECMs.

Methods and Results—

Rat arterial smooth muscle cells (ASMCs) transduced with bovine decorin cDNA by retroviral transfection (LDSN) exhibited enhanced contraction of collagen gels in vitro when compared with vector-only transduced (LXSN) cells. Addition of recombinant decorin to LXSN or LDSN cells did not stimulate contraction of collagen gels. Enhanced contraction of collagen by LDSN cells was unaffected by the metalloproteinase inhibitor GM6001. LDSN cells exhibited increased expression of type I collagen mRNA when compared with that of LXSN cells. Correspondingly, collagen gel contraction by LDSN cells was reduced by inhibition of collagen synthesis by 3,4-
l
-dehydroproline (L-DHP). Antibodies to α1β1-integrin, but not to α2β1-integrin, blocked collagen contraction by both LXSN and LDSN cells. However, LXSN and LDSN cells expressed similar levels of α1- and β1-integrin mRNAs.

Conclusions—

Decorin synthesized de novo by ASMCs increases type I collagen synthesis and enhances contraction of collagen gels. Regulated synthesis of decorin may be a useful therapeutic approach to reduce ECM volume in vascular disease.
Effects on Lipoprotein Subclasses of Combined Expression of Human Hepatic Lipase and Human apoB in Transgenic Rabbits
Authors: Rizzo Manfredi , Taylor John M. , Barbagallo Carlo M. , Berneis Kaspar , Blanche Patricia J. , Krauss Ronald M.
Published: November 2003

Objective—

The effects of combined expression of human hepatic lipase (HL) and human apolipoprotein B (apoB) on low-density lipoprotein (LDL) subclasses were examined in rabbits, a species naturally deficient in HL activity.

Methods and Results—

In apoB-transgenic rabbit plasma, >80% of the protein was found in the 1.006- to 1.050-g/mL fraction. Gradient gel electrophoresis (GGE) of this fraction revealed two distinct species, designated large and small LDL. A denser fraction (d=1.050 to 1.063 g/mL) contained small LDL as well as another discrete LDL subspecies, designated very small LDL. Expression of HL resulted in reductions in protein concentrations in the 1.006- to 1.050-g/mL density-gradient subfractions containing large (6.5±4.1 versus 32.6±12.0 mg/dL,
P
<0.005) and small LDL (59.6±17.4 versus 204.3±50.3 mg/dL,
P
<0.002). A concomitant small but not significant increase in protein concentration in the denser LDL fraction (48.0±28.2 versus 44.6±18.2 mg/dL) was due primarily to an increase in very small LDL (25.9±3.1 versus 9.6±5.4% of total LDL GGE densitometric area,
P
<0.002).

Conclusion—

These findings support a direct role for HL in regulating total plasma LDL concentrations as well as in the production of smaller, denser LDL from larger, more buoyant precursors.
Inflammation as a Risk Factor for Atrial Fibrillation
Authors: Aviles Ronnier J. , Martin David O. , Apperson-Hansen Carolyn , Houghtaling Penny L. , Rautaharju Pentti , Kronmal Richard A. , Tracy Russell P. , Van Wagoner David R. , Psaty Bruce M. , Lauer Michael S. , Chung Mina K.
Published: November 2003

Background—

The presence of systemic inflammation determined by elevations in C-reactive protein (CRP) has been associated with persistence of atrial fibrillation (AF). The relationship between CRP and prediction of AF has not been studied in a large population-based cohort.

Methods and Results—

CRP measurement and cardiovascular assessment were performed at baseline in 5806 subjects enrolled in the Cardiovascular Health Study. Patients were followed up for a mean of 6.9±1.6 (median 7.8) years. AF was identified by self-reported history and ECGs at baseline and by ECGs and hospital discharge diagnoses at follow-up. Univariate and multivariate analyses were used to assess CRP as a predictor of baseline and future development of AF. At baseline, 315 subjects (5%) had AF. Compared with subjects in the first CRP quartile (<0.97 mg/L), subjects in the fourth quartile (>3.41 mg/L) had more AF (7.4% versus 3.7%, adjusted OR 1.8, 95% CI 1.2 to 2.5;
P
=0.002). Of 5491 subjects without AF at baseline, 897 (16%) developed AF during follow-up. Baseline CRP predicted higher risk for developing future AF (fourth versus first quartile adjusted hazard ratio 1.31, 95% CI 1.08 to 1.58;
P
=0.005). When treated as a continuous variable, elevated CRP predicted increased risk for developing future AF (adjusted hazard ratio for 1-SD increase, 1.24; 95% CI 1.11 to 1.40;
P
<0.001).

Conclusions—

CRP is not only associated with the presence of AF but may also predict patients at increased risk for future development of AF.
Inhibition of Cyclic Strain-Induced Endothelin-1 Gene Expression by Resveratrol
Authors: Liu Ju-Chi , Chen Jin-Jer , Chan Paul , Cheng Ching-Feng , Cheng Tzu-Hurng
Published: November 2003

Resveratrol is a phytoestrogen naturally found in grapes and is among the major constituents of wine thought to have a cardioprotective effect. Endothelin-1 (ET-1) is a potent vasopressor synthesized by endothelial cells both in culture and in vivo. The aims of this study were to test the hypothesis that resveratrol may alter strain-induced ET-1 gene expression and to identify the putative underlying signaling pathways in endothelial cells. We show that resveratrol indeed potently inhibits strain-induced ET-1 secretion, ET-1 mRNA level, and ET-1 promoter activity. Resveratrol also inhibits strain-increased NADPH oxidase activity, reactive oxygen species formation, and extracellular signal–regulated kinases1/2 (ERK1/2) phosphorylation. Furthermore, pretreating cells with resveratrol or antioxidant
N
-acetyl-cysteine decreases strain-increased or hydrogen peroxide–increased ET-1 secretion, ET-1 promoter activity, and ET-1 mRNA and ERK1/2 phosphorylation. Using both the electrophoretic mobility shift assay and a reporter gene assay, resveratrol and
N
-acetyl-cysteine also attenuated the strain-stimulated activator protein-1 binding activity and activator protein-1 reporter activity. In summary, we demonstrate for the first time that resveratrol inhibits strain-induced ET-1 gene expression, partially by interfering with the ERK1/2 pathway through attenuation of reactive oxygen species formation. Thus, this study provides important new insights in the molecular pathways that may contribute to the proposed beneficial effects of resveratrol in the cardiovascular system.
Smoking and Risk of Hemorrhagic Stroke in Women
Authors: Kurth Tobias , Kase Carlos S. , Berger Klaus , Gaziano J. Michael , Cook Nancy R. , Buring Julie E.
Published: November 2003

Background and Purpose—

Several studies established smoking as a risk factor for ischemic stroke and subarachnoid hemorrhage (SAH) in men and women. A recent study added smoking as a risk factor for intracerebral hemorrhage (ICH) in men. In contrast, the impact of smoking on ICH in women is less clear.

Methods—

Prospective cohort study among 39 783 US women participating in the Women’s Health Study. Smoking habits and stroke occurrence were self-reported. Stroke cases were confirmed by medical record review. We used Cox proportional hazards model to evaluate the association of smoking with risk of total hemorrhagic stroke, ICH, and SAH. We categorized smoking into never, past, and current smokers of <15 and ≥15 cigarettes per day.

Results—

During 9 years of follow up, a total of 70 hemorrhagic strokes occurred, of which 40 were ICH and 29 were SAH. Never smokers and past smokers had equal rates of ICH and SAH. Current smokers of <15 cigarettes per day had a multivariable-adjusted relative risk (RR) of 1.93 (95% CI, 0.75 to 5.02) for total hemorrhagic stroke, 2.15 (95% CI, 0.62 to 7.43) for ICH, and 1.70 (95% CI, 0.38 to 7.60) for SAH. Women who smoked ≥15 cigarettes per day had RR of 3.29 (95% CI, 1.72 to 6.29) for total hemorrhagic stroke, 2.67 (95% CI, 1.04 to 6.90) for ICH, and 4.02 (95% CI, 1.63 to 9.89) for SAH compared with never smokers.

Conclusions—

This prospective study indicates an increased risk of total hemorrhagic stroke, ICH, and SAH in women who are current cigarette smokers. The risk increases with the amount of cigarettes smoked.
Predictors of Death Among Long-Term Stroke Survivors
Authors: Engstad Torgeir , Viitanen Matti , Arnesen Egil
Published: November 2003

Background and Purpose—

We evaluated the risk factors for death among long-term stroke survivors compared with stroke-free subjects.

Methods—

In 1997 we investigated 221 stroke survivors (mean, 9.4 years after index stroke) and 243 stroke-free subjects; both groups were recruited from a population-based health study. During the subsequent 5 years, all deaths (51 and 21 in the stroke and stroke-free groups, respectively) were registered.

Results—

The age- and sex-adjusted total mortality rate for the 5-year follow-up was 21.0% in the stroke group and 7.9% in the stroke-free group (
P
<0.0001), depending on different rates of cardiovascular deaths (
P
<0.0001). Better physical and social functioning (
P
<0.0001) and moderate use of alcohol (
P
≤0.004), the latter compared with no use, decreased risk of death, irrespective of stroke status. A myocardial infarction risk score had no impact on death in the stroke group, in contrast to the increased risk seen among the stroke-free group (
P
=0.0001).

Conclusions—

The long-term stroke survivors had significant excess risk of death compared with stroke-free subjects. Better physical and social functioning and moderate use of alcohol were associated with decreased risk, whereas a myocardial infarction risk score increased risk for death only in the stroke-free group.
Telemedicine in Emergency Evaluation of Acute Stroke
Authors: Handschu René , Littmann Rebekka , Reulbach Udo , Gaul Charly , Heckmann Josef G. , Neundörfer Bernhard , Scibor Mateusz
Published: November 2003

Background and Purpose—

In acute stroke care, rapid but careful evaluation of patients is mandatory but requires an experienced stroke neurologist. Telemedicine offers the possibility of bringing such expertise quickly to more patients. This study tested for the first time whether remote video examination is feasible and reliable when applied in emergency stroke care using the National Institutes of Health Stroke Scale (NIHSS).

Methods—

We used a novel multimedia telesupport system for transfer of real-time video sequences and audio data. The remote examiner could direct the set-top camera and zoom from distant overviews to close-ups from the personal computer in his office. Acute stroke patients admitted to our stroke unit were examined on admission in the emergency room. Standardized examination was performed by use of the NIHSS (German version) via telemedicine and compared with bedside application.

Results—

In this pilot study, 41 patients were examined. Total examination time was 11.4 minutes on average (range, 8 to 18 minutes). None of the examinations had to be stopped or interrupted for technical reasons, although minor problems (brightness, audio quality) with influence on the examination process occurred in 2 sessions. Unweighted κ coefficients ranged from 0.44 to 0.89; weighted κ coefficients, from 0.85 to 0.99.

Conclusions—

Remote examination of acute stroke patients with a computer-based telesupport system is feasible and reliable when applied in the emergency room; interrater agreement was good to excellent in all items. For more widespread use, some problems that emerge from details like brightness, optimal camera position, and audio quality should be solved.
Iron and Iron-Handling Proteins in the Brain After Intracerebral Hemorrhage
Authors: Wu Jimin , Hua Ya , Keep Richard F. , Nakamura Takehiro , Hoff Julian T. , Xi Guohua
Published: November 2003

Background and Purpose—

Evidence indicates that brain injury after intracerebral hemorrhage (ICH) is due in part to the release of iron from hemoglobin. Therefore, we examined whether such iron is cleared from the brain and the effects of ICH on proteins that may alter iron release or handling: brain heme oxygenase-1, transferrin, transferrin receptor, and ferritin.

Methods—

Male Sprague-Dawley rats received an infusion of 100 μL autologous whole blood into the right basal ganglia and were killed 1, 3, 7, 14, or 28 days later. Enhanced Perl’s reaction was used for iron staining, and brain nonheme iron content was determined. Brain heme oxygenase-1, transferrin, transferrin receptor, and ferritin were examined by Western blot analysis and immunohistochemistry. Immunofluorescent double labeling was performed to identify which cell types express ferritin.

Results—

ICH upregulated heme oxygenase-1 levels and resulted in iron overload in the brain. A marked increase in brain nonheme iron was not cleared within 4 weeks. Brain transferrin and transferrin receptor levels were also increased. In addition, an upregulation of ICH on ferritin was of very long duration.

Conclusions—

The iron overload and upregulation of iron-handling proteins, including transferrin, transferrin receptor, and ferritin, in the brain after ICH suggest that iron could be a target for ICH therapy.
IL-7–dependent human leukemia T-cell line as a valuable tool for drug discovery in T-ALL
Authors: Barata Joao T. , Boussiotis Vassiliki A. , Yunes Jose A. , Ferrando Adolfo A. , Moreau Lisa A. , Veiga J. Pedro , Sallan Stephen E. , Look A. Thomas , Nadler Lee M. , Cardoso Angelo A.
Published: November 2003

The specific targeting of critical signaling molecules may provide efficient therapies for T-cell acute lymphoblastic leukemia (T-ALL). However, target identification and drug development are limited by insufficient numbers of primary T-ALL cells and by their high rate of spontaneous apoptosis. We established a human interleukin-7 (IL-7)–dependent T-ALL cell line, TAIL7, that maintains several biologic and signaling properties of its parental leukemia cells. TAIL7 cells are pre–T-ALL cells that proliferate in response to IL-7 and IL-4. IL-7 stimulation of TAIL7 cells prevents spontaneous in vitro apoptosis and induces cell activation and cell cycle progression. The signaling events triggered by IL-7 include down-regulation of p27kip1 and hyperphosphorylation of retinoblastoma protein (Rb). Stimulation of TAIL7 cells by IL-7 leads to phosphorylation of Janus kinase 3 (JAK3), signal transducer and activator of transcription 5 (STAT5), Akt/PKB (protein kinase B), and extracellular-regulated kinase 1 and 2 (Erk1/2). Importantly, specific blockade of JAK3 by its inhibitor WHI-P131 abrogates the IL-7–mediated proliferation and survival of TAIL7 cells, suggesting that activation of JAK3 is critical for IL-7 responsiveness by these cells. Because TAIL7 cells seem to be a biologic surrogate for primary leukemia T cells, this cell line constitutes a valuable tool for the study of the signaling pathways implicated in T-ALL. Exploitation of this cell line should allow the identification of molecular targets and promote the rational design and validation of antileukemia signaling inhibitors.
Relationship between REL amplification, REL function, and clinical and biologic features in diffuse large B-cell lymphomas
Authors: Houldsworth Jane , Olshen Adam B. , Cattoretti Giorgio , Donnelly Gerard B. , Teruya-Feldstein Julie , Qin Jing , Palanisamy Nallasivam , Shen Yingjing , Dyomina Katerina , Petlakh Marina , Pan Qiulu , Zelenetz Andrew D. , Dalla-Favera Riccardo , Chaganti R. S. K.
Published: November 2003

Although it has been suggested that REL is the critical target gene of 2p12-16 amplification in diffuse large B-cell lymphoma (DLBCL), little experimental evidence supports this notion. In the present study, we sought to evaluate the relationship between REL amplification and REL function in a panel of 46 newly diagnosed DLBCLs and to correlate with DLBCL subgroups as identified by gene expression profiles and clinical features. The results indicate that amplification of the REL locus is not associated with accumulation of the active form of REL, as evaluated by immunofluorescence analysis. Upon subgrouping of the DLBCL cases based on gene expression signatures, REL amplification was detected in all subgroups, while high levels of nuclear-located REL were more frequently detected in activated B-cell–like DLBCL. Correlative analyses of REL copy number and REL nuclear accumulation with clinical parameters did not reveal any significant associations. Together these results indicate that 2p12-16 amplification does not lead to abnormal REL activation, suggesting that REL may not be the functional target of the amplification event. Nonetheless, these data indicate that DLBCLs are heterogeneous with respect to REL and thus nuclear factor–κB (NF-κB) activity.
Microglia, macrophages, perivascular macrophages, and pericytes: a review of function and identification
Authors: Guillemin Gilles J , Brew Bruce J
Published: November 2003

The phenotypic differentiation of systemic macrophages that have infiltrated the central nervous system, pericytes, perivascular macrophages, and the “real” resident microglial cells is a major immunocytochemical and immunohistochemical concern for all users of cultures of brain cells and brain sections. It is not only important in assessing the purity of cell cultures; it is also of fundamental importance in the assessment of the pathogenetic significance of perivascular inflammatory phenomena within the brain. The lack of a single membranous and/or biochemical marker allowing conclusive identification of these cells is still a major problem in neurobiology. This review briefly discusses the functions of these cells and catalogs a large number of membranous and biochemical markers, which can assist in the identification of these cells.