bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human heme oxygenase: Cell cycle‐dependent expression and DNA microarray identification of multiple gene responses after transduction of endothelial cells
Authors: Abraham N.G. , Scapagnini G. , Kappas A. 
Published: November 2003

AbstractThe purpose of the present study was to examine the role of human heme oxygenase (human HO‐1) in cell cycle progression following exposure to heme or human HO‐1 gene transfer and to identify target genes associated with human HO‐1‐meditated increases in cell cycle progression using cDNA microarray technology. Heme‐induced robust human HO‐1 expression in quiescent human microvessel endothelial cells cultured in 1% FBS and the levels of human HO‐1 expression progressively declined without a change in the cell cyclin. To identify genes regulated by human HO‐1 in the cell cycle, human endothelial cells were transduced with a retroviral vector encoded with human HO‐1 gene or an empty vector. Transgene expression and functionality of the recombinant protein were assessed by Western blotting, enzyme activity, carbon monoxide, cGMP production, and cell cycle analysis. Human cDNA gene array and quantitative real‐time RT‐PCR were used to identify both known and novel differentially expressed genes in cells overexpressing human HO‐1. Major findings were upregulation of several genes associated with cell cycle progression, including cyclin E and D; downregulation of cyclin‐dependent kinase inhibitors p21 and p27, cyclin‐dependent kinases 2, 5, and 6, and monocyte chemoattractant protein‐1; and upregulation of growth factors, including vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor I (VEGFRI), endothelial growth factor (EGF) and hepatic‐derived growth factor (HDGF). These findings identify an array of gene responses to overexpression of human HO‐1 and elucidate new aspects of human HO‐1 signaling involved in cell growth. © 2003 Wiley‐Liss, Inc.
Onset and duration of cytomegalovirus immediate early 1 mRNA expression in the blood of renal transplant recipients
Authors: Goossens Valère J. , Christiaans Maarten H.L. , Blok Marinus J. , Terporten Peter H.W. , Sillekens Peter , Lukacsi Angela , Van Hooff Johannes P. , Bruggeman Cathrien A. 
Published: November 2003

AbstractHuman cytomegalovirus (CMV) messenger (m) RNA expression in circulating leukocytes reflects directly viral activity in the human host. In this study, sixty‐nine patients were monitored prospectively for CMV infection and mRNA expression during the first year after renal transplantation. Of the 69 recipients, 58 (84%) recipients were positive for CMV immediate early 1 (IE1) mRNA as detected by nucleic acid sequence‐based amplification. The median onset of IE1 expression started at day 22 after transplantation and continued for a median duration of 82 days. IE1 mRNA expression started significantly earlier in recipients who developed an active CMV infection (P = 0.001) and in mycophenolate mofetil (MMF) treated recipients (P = 0.002). The duration of IE1 mRNA expression was significantly longer in recipients that had previously an early onset of IE1 mRNA expression (P = 0.001) and in recipients with active CMV infection (P = 0.007). Remarkably, longer prednisolone intake was correlated with a significantly (P = 0.02) shorter duration of IE1 expression compared to a longer duration of IE1 expression in recipients with only a short prednisolone intake. In recipients infected with glycoprotein B (gB) type 1 CMV strains, the duration of IE1 expression was significantly (P = 0.04) shorter compared to recipients infected with non‐gB type 1 CMV strains (64 days vs. 150 days). The study indicates that multiple factors play a role in the onset and/or duration of CMV IE1 mRNA expression, for example, MMF treatment, prednisolone intake, and gB type of the specific CMV strain. The clinical significance of these correlations remains to be studied in more detail. J. Med. Virol. 72:94–101, 2004. © 2004 Wiley‐Liss, Inc.
Changing seroepidemiology of hepatitis B, C, and D virus infections in high‐risk populations
Authors: Huo Teh‐Ia , Wu Jaw‐Ching , Wu Shiow‐Ing , Chang An‐Lung , Lin Shih‐Ku , Pan Chun‐Hung , Huang Yi‐Hsiang , Chang Full‐Young , Lee Shou‐Dong 
Published: November 2003

AbstractNeedle‐sharing and sexual contact are important transmission routes of hepatitis B, C, and D virus (HBV, HCV, HDV) infection. This study aimed to investigate the current status of these viral infections among high‐risk populations including prostitutes and intravenous (i.v.) drug users, compared with the prevalence rate reported previously to examine the changing seroepidemiology. Of the 916 female prostitutes, 79 (9%) were positive for antibody to HCV (anti‐HCV), 111 (12%) were positive for HBV surface antigen (HBsAg), and 5 (5%) had antibody to HDV (anti‐HDV). The prevalence rate was significantly lower compared to that in 1989–1991 (12%, P = 0.037) for HCV infection, and to that in 1988 (59%) and 1996 (40%) (P < 0.0001) for HDV infection. Of the 494 i.v. drug users, 87 (18%) patients were HBsAg carriers and 12 (14%) were anti‐HDV‐positive. The prevalence rate of HDV infection was significantly lower than that reported in 1985 (79%, P < 0.0001). Among the 443 tested i.v. drug users, 182 (41%) were anti‐HCV‐positive, significantly lower than that in 1985 (53%, P = 0.026). Of the 263 male prostitutes, 11 (4%) were anti‐HCV‐positive, 45 (17%) were HBsAg‐positive, and 7 (16%) were anti‐HDV‐positive. Of the 129 illegal immigrant prostitutes, 7 (5%) were anti‐HCV‐positive, 15 (12%) were HBsAg‐positive and none were positive for anti‐HDV. In conclusion, the findings indicate a declining prevalence of HCV and HDV infections among drug users and prostitutes over the past 16 years. Male prostitutes and immigrant prostitutes are new “high‐risk” populations and may become a reservoir for disease transmission. J. Med. Virol. 72:41–45, 2004. © 2004 Wiley‐Liss, Inc.
Genetic heterogeneity of the precore and the core promoter region of genotype C hepatitis B virus during lamivudine therapy
Authors: Kuwahara Reiichiro , Kumashiro Ryukichi , Murashima Shiro , Ogata Kei , Tanaka Kazuo , Hisamochi Akiko , Hino Teruko , Ide Tatsuya , Tanaka Eisuke , Koga Yuriko , Sata Michio 
Published: November 2003

AbstractIt has been reported that spontaneous or interferon (IFN)‐induced hepatitis B e (HBe) seroconversion has usually been associated with the development of a stop codon in the precore region. However, the difference between lamivudine‐induced seroconversion and spontaneous or IFN‐induced seroconversion is not known. The aim of this study was to investigate the correlation between the evolution of the precore and core promoter mutations and lamivudine‐induced seroconversion. Forty‐five patients with chronic hepatitis B virus (HBV) infection who were treated with lamivudine for more than 1 year were enrolled. The nucleotide sequence of the precore and core promoter region was determined before and after treatment with lamivudine for 1 year. Among 29 patients who were hepatitis B e antigen (HBeAg)‐positive before treatment, 12 (41.3%) lost HBeAg during the course of treatment for 1 year. Of these, eight patients (66.7%) still had precore wild type HBV after 1 year. After 1 year, reversion to precore wild type HBV was detected in 11 (64.7%) of 17 patients who had precore mutant HBV before treatment. Twelve (70.6%) of 17 patients who were persistently HBeAg‐positive had precore wild type HBV before and after treatment for 1 year. Despite the loss of HBeAg, two thirds of the patients still had precore wild type HBV after the 1‐year treatment. It is suggested that lamivudine‐induced seroconversion differs from spontaneous or IFN‐induced seroconversion in the change of nucleotides in the precore region. The reversion in the precore region may be caused by the difference of drug‐susceptibility to lamivudine. The antiviral effect of lamivudine may be more effective in the precore mutant HBV than in the precore wild type HBV. J. Med. Virol. 72:26–34, 2004. © 2004 Wiley‐Liss, Inc.
Distribution of TT virus genomic groups 1–5 in Brazilian blood donors, HBV carriers, and HIV‐1‐infected patients
Authors: Devalle Sylvie , Niel Christian 
Published: November 2003

AbstractHuman isolates of the highly prevalent TT virus (TTV) have been classified into five major genomic groups (1–5). The geographical distribution of the groups throughout the world is not well known. Five different PCR assays were developed in an attempt to amplify specifically TTV DNAs of each genomic group. Serum samples collected from 72 Brazilian adults (24 voluntary blood donors, 24 hepatitis B virus (HBV) carriers, and 24 human immunodeficiency virus type 1 (HIV‐1)‐infected patients) were tested. TTV DNA from at least one genomic group was detected in 11 (46%) blood donors, 13 (54%) HBV carriers, and 24 (100%) HIV‐1 patients. All five genomic groups were detected in the three populations, with the exception of group 2 in blood donors. Some samples, negative with all five specific assays, were positive with the commonly used untranslated region (UTR) PCR system. On the other hand, TTV DNA was detected in some samples by using specific assays but not with the UTR PCR. Mixed infections with 2–5 TTV isolates from different groups were detected in 21% blood donors, 29% HBV carriers, and 71% HIV‐1 patients. Fifteen PCR products (three obtained with each assay) were sequenced. Most sequences showed high (>86%) homology with those of TTV isolates belonging to their presumed groups. However, three sequences had low homology with all TTV sequences available from the DNA databanks. In conclusion, TTV isolates belonging to all five known genomic groups circulate in Brazil, and the results suggest the existence of new and as yet uncharacterised major genomic groups. J. Med. Virol. 72:166–173, 2004. © 2004 Wiley‐Liss, Inc.
Neuroprotective effect of adenine on purkinje cell survival in rat cerebellar primary cultures
Authors: Watanabe Shun , Yoshimi Yoji , Ikekita Masahiko 
Published: November 2003

AbstractAlthough adenosine or ATP is known to control various physiological functions in the brain, including synaptic transmission, neuronal cell death, and neurite outgrowth via P1 or P2 purinergic receptors in the nervous system, little is known about the functions of many other purine derivatives. We examined the effects of various purines on survival in the cerebellar cortex of Purkinje cells with large cell bodies and highly branched dendrites, and it was found that some purine and pyrimidine derivatives influence Purkinje cell survival. Treatment with adenine, guanine, guanosine, guanine nucleotides, and uracil nucleotides protected Purkinje cells from cell death in the cerebellar primary cultures. Among the effective compounds, adenine had the most potent survival activities on Purkinje cells. Other adenine‐based purines such as adenosine, AMP, ADP, and ATP did not promote Purkinje cell survival. Furthermore, metabolic inhibitors of adenine had no effect on the protective ability of adenine for Purkinje cells, suggesting that adenine itself, not adenine metabolites, maintains Purkinje cell survival. These results suggest that adenine is involved in the control of Purkinje cell survival in cerebellar primary cultures via a novel adenine‐dependent mechanism. © 2003 Wiley‐Liss, Inc.
Effect of excess extracellular glutamate on dendrite growth from cerebral cortical neurons at 3 days in vitro: Involvement of NMDA receptors
Authors: Monnerie Hubert , Shashidhara Shalini , Le Roux Peter D. 
Published: November 2003

AbstractGlutamate is an important regulator of dendrite development; however, during cerebral ischemia, massive glutamate release can lead to neurodegeneration and death. An early consequence of glutamate excitotoxicity is dendrite injury, which often precedes cell death. We examined the effect of glutamate on dendrite growth from embryonic day 18 (E18) mouse cortical neurons grown for 3 days in vitro (DIV) and immunolabeled with anti‐microtubule‐associated protein (MAP)2 and anti‐neurofilament (NF)‐H, to identify dendrites and axons, respectively. Cortical neurons exposed to excess extracellular glutamate (100 μM) displayed reduced dendrite growth, which occurred in the absence of cell death. This effect was mimicked by the ionotropic glutamate receptor agonist N‐methyl‐D‐aspartate (NMDA) and blocked by the ionotropic glutamate receptor antagonist kynurenic acid and the NMDA receptor‐specific antagonist MK‐801. The non‐NMDA receptor agonist AMPA, however, did not affect process growth. Neither NMDA nor AMPA influenced neuron survival. Immunolabeling and Western blot analysis of NMDA receptors using antibodies against the NR1 subunit, demonstrated that immature cortical neurons used in this study, express NMDA receptors. These results suggest that excess glutamate decreases dendrite growth through a mechanism resulting from NMDA receptor subclass activation. Furthermore, these data support the possibility that excess glutamate activation of NMDA receptors mediate both cell death in mature neurons and the inhibitory effect of excess glutamate on dendrite growth in immature neurons or in the absence of cell death. © 2003 Wiley‐Liss, Inc.
GeneChip analysis of hippocampal gene expression profiles of short‐ and long‐attack‐latency mice: Technical and biological implications
Authors: Feldker Dorine E.M. , Datson Nicole A. , Veenema Alexa H. , Proutski Vitali , Lathouwers Desiree , de Kloet E. Ron , Vreugdenhil Erno 
Published: November 2003

AbstractTo gain insight into the molecular mechanisms underlying the behavioral differences between two mouse lines genetically selected for long and short attack latency (LAL and SAL mice, respectively), we have recently applied the large‐scale gene expression profiling method known as serial analysis of gene expression (SAGE) to generate hippocampal gene expression profiles of these mice. The aim of the present study is to extend and validate the SAGE expression profile of hippocampi of LAL and SAL mice using GeneChips (Affymetrix, Santa Clara, CA; one array per mouse, n = 5 per mouse line). As was the case with SAGE, GeneChips detect only medium‐ to high‐abundance genes in the hippocampus. Extensive analysis of GeneChip data using very stringent parameters shows differential expression of 122 genes, all except one of which were expressed at higher levels in LAL mice (P < 0.01). As predicted by SAGE, our data indicate higher expression of several cytoskeleton genes in LAL mice, suggesting longer axonal and dendritic projections in the hippocampus of these mice. This is consistent with our tentative model, in which the behavioral differences between LAL and SAL mice may be related to structural differences in the hippocampus. In addition, a group of 76 genes with diverse biological function and 46 expressed sequence tags (ESTs) were all expressed at higher levels in LAL mice. A novel finding in this study was the significantly lower expression of only a single gene, growth arrest‐specific gene (gas5), in LAL mice. As gas5 does not encode a protein but several small nuclear RNAs, our data suggest that small RNAs may contribute to the molecular mechanisms underlying the extreme behavioral differences between LAL and SAL mice. © 2003 Wiley‐Liss, Inc.
Adenoviral‐mediated expression of functional na+ channel β1 subunits tagged with a yellow fluorescent protein
Authors: Fry Mark , Porter Donna M. , Maue Robert A. 
Published: November 2003

AbstractVoltage‐gated sodium (Na+) channels typically contain a pore‐forming α subunit and one or two auxiliary β subunits. Although initial characterization of known α and β subunits has been facilitated by expression in heterologous cells, to understand fully the differences between individual subunits and the functional consequences of selective subunit expression, there is a need to acutely manipulate expression in cells that endogenously express Na+ channels. To this end, we have constructed a recombinant adenovirus containing a cDNA for a mouse Na+ channel β1 subunit with a yellow fluorescent protein fused to its C‐terminus (Ad‐β1‐EYFP), and with fluorescence microscopy detected β1‐EYFP expression in primary cerebellar neurons and Chinese hamster ovary (CHO) cells upon transduction with this adenovirus, including expression in the plasma membrane. Consistent with this, patch clamp recordings confirmed that Na+ currents in CHO cells expressing mouse Nav1.4 α subunits were appropriately modified by the viral‐mediated expression of β1‐EYFP subunits. The results demonstrate that adenoviral‐mediated gene delivery can be used effectively to express epitope‐tagged Na+ channel subunits with properties similar to wild‐type subunits, and suggest that Ad‐β1‐EYFP will be a useful reagent for investigating Na+ channels in a variety of excitable cell types, including neurons. © 2003 Wiley‐Liss, Inc.
Loss of pro‐apoptotic BH3‐only Bcl‐2 family member bim does not protect mutant Lurcher mice from neurodegeneration
Authors: Bouillet Philippe , Robati Mikara , Adams Jerry M. , Strasser Andreas 
Published: November 2003

AbstractLurcher (lc) mice have a semi‐dominant mutation in the gene encoding the δ2 glutamate receptor (GRID2). The resulting constitutive activity of this receptor in heterozygous +/lc (grid+/lc) and homozygous (gridlc/lc) mice leads to the death of all cerebellar Purkinje cells and most afferent granule neurons. Some studies have indicated that the death of Purkinje cells occurs by apoptosis, and the secondary loss of granule neurons has been shown to require the pro‐apoptotic Bcl‐2 family member Bax. The BH3‐only protein Bim has been shown to contribute to cytokine withdrawal‐induced apoptosis of sympathetic neurons and to be responsible for the kidney degeneration in mice lacking the pro‐survival protein Bcl‐2. Because Bim is expressed strongly in cerebellar Purkinje cells, we have examined whether it has a role in their death in mutant Lurcher mice. Our studies show that Bim deficiency does not modify the Lurcher phenotype, ruling out an indispensable role for Bim in this neurodegenerative disease. © 2003 Wiley‐Liss, Inc.
Transcriptional regulation through glutamate receptors: Involvement of tyrosine kinases
Authors: López‐Bayghen Esther , Aguirre Adán , Ortega Arturo 
Published: November 2003

AbstractGlutamate receptors play a key role in neuronal plasticity, learning and memory, and in several neuropathologies. Short‐term and long‐term changes in synaptic efficacy are triggered by glutamate. Although an enhanced glutamate‐dependent tyrosine phosphorylation has been described in several systems, its role in membrane‐to‐nuclei signaling is unclear. Taking advantage of the fact that the gene encoding the chick kainate‐binding protein undergoes a glutamate‐dependent transcriptional regulation via an activator protein‐1 (AP‐1) site, we evaluated the involvement of tyrosine kinases in this process. We describe here the participation of receptor and non‐receptor tyrosine kinases in the signaling cascade triggered by glutamate. Our results suggest that in Bergmann glia cells, glutamate receptors transactivate receptor tyrosine kinases, favoring the idea of a complex network of signals activated by this excitatory neurotransmitter that results in regulation of gene expression. © 2003 Wiley‐Liss, Inc.
Mild carbon monoxide exposure and auditory function in the developing rat
Authors: Stockard‐Sullivan Janet E. , Korsak Rose A. , Webber Douglas S. , Edmond John 
Published: November 2003

AbstractWe have examined the influence of chronic mild exposure to carbon monoxide (CO) on cognitive (learning) and auditory function in the developing rat. We have demonstrated that the auditory pathway is compromised at exposures less than 50 ppm, whereas learning was not influenced at 100 ppm. Artificially reared rat pups were exposed to CO during the brain growth spurt and onset of myelination. Spatial learning was assessed using the Morris Water Maze and three tests of auditory function: (1) auditory brainstem conduction times; (2) the amplitude of the eighth nerve's action potential; and (3) otoacoustic emissions carried out on rat pups (age 22– 24 days). The pups were gastrostomy‐reared on a rat milk substitute and chronically exposed to CO at discrete concentrations in the range of 12–100 ppm from 6 days of age to post‐weaning at 21–23 days of age. We found no difference in auditory brainstem conduction times at all CO concentrations in comparison to non‐exposed controls. There was a difference in otoacoustic emissions for test and controls at CO concentrations of 50 ppm but not at lower concentrations. There was a consistent attenuation of the amplitude of the eighth nerve's action potential, even at the lowest CO exposure examined. The attenuation of the amplitude of the action potential of the eighth nerve at 50 ppm carbon monoxide exposure did not completely recover by 73 days of age. We conclude that prolonged mild exposure to carbon monoxide during development causes measurable functional changes at the level of the eighth cranial nerve. © 2003 Wiley‐Liss, Inc.
Estrogen and cognition: Applying preclinical findings to clinical perspectives
Authors: Gibbs Robert B. , Gabor Rachel 
Published: November 2003

AbstractThe effects of hormone replacement therapy on brain aging and cognition are an important public health issue, which, despite much research and debate, has not yet been resolved. In this Mini‐Review, we describe how much of the clinical literature takes on new meaning when interpreted in light of recent preclinical data. We predict, based on these data, that hormone replacement therapy will in fact provide substantial benefit with respect to age‐related cognitive decline, provided that therapy is administered in an appropriate regimen and is initiated within a window of time following the loss of ovarian function. The application of these data to recent clinical findings is discussed. © 2003 Wiley‐Liss, Inc.
Mild carbon monoxide exposure diminishes selectively the integrity of the cochlea of the developing rat
Authors: Lopez Ivan , Acuna Dora , Webber Douglas S. , Korsak Rose A. , Edmond John 
Published: November 2003

AbstractRat pups were chronically exposed to carbon monoxide (CO) concentrations (12 or 25 ppm) in air starting at day 8, through 22 days of age, to examine the changes in the peripheral auditory system. Gastrostomy‐reared rat pups, with or without CO exposure, were used and compared with mother‐reared pups. The organ of Corti and the neurons of the spiral ganglion were analyzed for their morphology by using immunochemical and histological techniques. The inner and outer hair cells in the organ of Corti of animals exposed to 12 and 25 ppm CO were not different from the controls. However, at 25 ppm CO exposure, the nerve terminals innervating the inner hair cells were swollen. The somata of neurons in the spiral ganglion showed mild changes in the cytoplasm, and signs of mild vacuolization were observed in myelin covering their central processes. Synaptophysin, a marker for synaptic vesicles, and choline acetyltransferase, a marker for cholinergic terminals, showed no difference in immunoreactivity in CO exposed animals at 12 and at 25 ppm when compared with their age‐matched controls. Also, Na+K+ ATPase immunoreactivity patterns were normal compared with controls. Three enzymes were significantly reduced at the 25 ppm CO exposure: Cytochrome oxidase, NADH‐TR, and calcium ATPase were decreased in both the organ of Corti and the neurons of the spiral ganglion, and decreased immunostaining for the neurofilament and myelin basic proteins was found. We conclude that components of the cochlea are selectively affected by mild chronic CO exposure during development. © 2003 Wiley‐Liss, Inc.