bluuebunny/crossref_metadata_2025_split huggingface dataset:
Magnetic resonance myocardial first‐pass perfusion imaging: Parameter optimization for signal response and cardiac coverage
Authors: Bertschinger Katharina M. , Nanz Daniel , Buechi Martin , Luescher Thomas F. , Marincek Borut , von Schulthess Gustav K. , Schwitter Juerg 
Published: August 2002

AbstractFast imaging techniques allow monitoring of contrast medium (CM) first‐pass kinetics in a multislice mode. Employing shorter recovery times improves cardiac coverage during first‐pass conditions, but potentially flattens signal response in the myocardium. The aim of this study was therefore to compare in patients with suspected coronary artery disease (CAD) two echo‐planar imaging strategies yielding either extended cardiac coverage or optimized myocardial signal response (protocol A/B, six/four slices; preparation pulse, 60°/90°; delay time, 10/120 msec; readout flip angle, 10°/50°; respectively). In phantoms and myocardium of normal volunteers (N= 10) the CM‐induced signal increase was 2.5–3 times higher with protocol B (P < 0.005) than with protocol A. For the detection of individually diseased coronary arteries (≥1 stenosis with ≥50% diameter reduction on quantitative coronary angiography (QCA)), receiver‐operator characteristics of protocol B (signal upslope in 32 sectors/heart) yielded a sensitivity/specificity of 82%/73%, which was superior to protocol A (P < 0.05, N= 14). For the overall detection of CAD, the sensitivity/specificity of protocol B was 85%/81%. An adequate signal response in the myocardium is crucial for a reliable detection of perfusion deficits during first‐pass conditions. The presented protocol B detects CAD with a sensitivity and specificity similar to scintigraphic techniques. J. Magn. Reson. Imaging 2001;14:556–562. © 2001 Wiley‐Liss, Inc.
Interfaces for coupled liquid‐phase separation/mass spectrometry techniques. An update on recent developments
Authors: Gelpí Emilio 
Published: August 2002

AbstractAn update is presented covering the latest developments in the interfacing of liquid‐phase separation systems and mass spectrometers. The interfacing devices presented are those developed for continuous‐flow matrix‐assisted laser desorption/ionization, micro‐ and nano‐liquid chromatography/masspectrometry (MS), capillary electrophoresis/MS and on‐chip separation technologies/MS. From the information that can be found in the most recent literature on the topic, it is evident that the trend towards the miniaturization of separation and interface devices is gaining ground. This can be rationalized by the substantial gains in sensitivity for the detection and study of extremely low levels of analytes and especially of high molecular mass biopolymers. Copyright © 2002 John Wiley & Sons, Ltd.
Prevalence and distribution of human herpesvirus 6 variants A and B in adult human brain
Authors: Chan Paul K.S. , Ng Ho‐Keung , Hui Mamie , Cheng Augustine F. 
Published: August 2002

AbstractThe presence of human herpesvirus 6 (HHV‐6) in brain tissues of 40 consecutive post‐mortem cases was examined. For each case, autopsy samples were collected from the cerebellum, frontal, temporal, parietal and occipital lobes of both sides of the brain. HHV‐6 DNA was detected by nested polymerase chain reaction and characterised into variants A and B. Overall, 97/400 (24.3%) samples were positive for HHV‐6 DNA with 16 being variant A and 81 being variant B, but none of the samples harboured both variants. When analysed by patient, 34/40 (85%) had HHV‐6 DNA detected in the brain. The viral DNA positivity did not show significant variation with gender and age. Four patients harboured variant A, 23 harboured variant B, and seven had both variants at different positions. The results indicate that both HHV‐6A and HHV‐6B are neurotropic and human brain may be another site for latency. HHV‐6B was detected in brain tissues of a majority (75%) of the studied population and with a widespread distribution within the brain. Although the observed prevalence of HHV‐6A in brain is lower (27.5%), in view of its lower seroprevalence, the neuroinvasive potential of variant A may be comparable to that of variant B. Although both variants are potential pathogens for the nervous system, the fact that they can exist, probably for most of the time, as commensals in human brain needs to be considered when interpreting their roles in neuropathology. J. Med. Virol. 64:42–46, 2001. © 2001 Wiley‐Liss, Inc.
CV genotype and “silent” HBV coinfection: Two main risk factors for a more severe liver disease
Authors: Sagnelli Evangelista , Coppola Nicola , Scolastico Carlo , Mogavero Anna Rita , Filippini Pietro , Piccinino Felice 
Published: August 2002

AbstractTo evaluate whether HCV genotype and a “silent” HBV infection may be related to a more severe clinical presentation of liver disease, 205 anti‐HCV/HCV‐RNA positive, HBsAg/anti‐HBs negative patients with chronic hepatitis (113 males and 92 females; median age 55 years, range 18–77), were studied on presentation at the Liver Unit from January 1993 to December 1997. Presence of serum anti‐HBc, in the absence of HBsAg and anti‐HBs, was considered a marker of “silent” HBV infection. Of the 205 patients, 134 had undergone percutaneous liver biopsy. Two main diagnosis groups were established: the mild liver disease group (76 patients), and the severe liver disease group (109 patients); 20 patients who had refused to undergo liver biopsy were not included in the clinical and virological evaluation because the diagnosis was uncertain. The prevalence of severe liver disease was similar in the genotype 1 and non‐1 groups (61.3% of 98 patients with genotype 1 and 52.9% of 70 patients with a non‐1 genotype). Instead, the 88 patients with “silent” HBV infection showed a higher percentage of severe liver disease than the 97 anti‐HBc negative patients (72.7% vs. 46.4%, respectively: P < 0.0005). Of the 88 anti‐HBc positive patients, the prevalence of those with severe liver disease was similar in the 32 cases with serum HBV‐DNA as detected by PCR and in the 56 HBV‐DNA negative (81.2% vs. 67.8%, P = 0.4). The relation between “silent” HBV infection and severe liver disease was observed both in genotype 1 and non‐1 infected patients. Nevertheless, the anti‐HBc negative patients infected by genotype 1 showed a severe liver disease more frequently than those infected by a non‐1 genotype, with a difference that is significant to the statistical analysis (P < 0.05). The findings suggest that “silent” HBV infection in anti‐HCV positive chronic hepatitis enhances the severity of the liver disease. Evidence was also found that in patients without “silent” HBV infection there is a correlation between the presence of HCV genotype 1 and the severity of liver disease. J. Med. Virol. 64:350–355, 2001. © 2001 Wiley‐Liss, Inc.
High prevalence of TT virus‐related DNA (90%) and diverse viral genotypes in norwegian blood donors
Authors: Huang Li‐Yue , Jonassen Tom Øystein , Hungnes Olav , Grinde Bjørn 
Published: August 2002

AbstractEarly estimates of the prevalence of TTV viremia in healthy adults of developed countries were in the order of 1–10 %, while similar estimates in Third World countries were considerably higher. Using three different PCRs, TTV‐related DNA was detected in serum from 180 out of the 201 Norwegian blood donors tested, indicating that these viruses are almost universally present in adults. Sequence analysis revealed heterogeneity similar to what is found world‐wide. The data suggest that the previous discrepancy in prevalences might be related to a lower serum concentration of virus in developed countries. The high prevalence adds evidence to the benign nature of the virus. J. Med. Virol. 64:381–386, 2001. © 2001 Wiley‐Liss, Inc.
Development and significance of resistance to protease inhibitors in HIV‐1‐infected adults under triple‐drug therapy in clinical practice
Authors: Romano Laura , Venturi Giulietta , Giomi Saverio , Pippi Luigi , Valensin Pier E. , Zazzi Maurizio 
Published: August 2002

AbstractDevelopment of drug resistance is considered a major cause for failure of antiretroviral therapy in human immunodeficiency virus type 1 (HIV‐1)‐infected patients adherent to treatment. However, the rate of emergence and the significance of HIV‐1 drug resistance in clinical practice have been not investigated thoroughly. Selection of HIV‐1 variants that are genotypically resistant to protease inhibitors was studied in all the patients (n = 169) who completed at least 18 months of treatment with a protease inhibitor plus two nucleoside reverse transcriptase inhibitors at two urban Italian hospitals. HIV‐1 carrying primary protease inhibitor resistance mutations was detected in 70 (41.4%) patients. The estimated proportion of patients developing genotypic resistance to protease inhibitors at 12 and 24 months was 18.3% (95% CI, 12.5–24.2%) and 33.9% (95% CI, 26.4–41.5%), respectively. Independent predictors of development of resistance to protease inhibitors were higher HIV‐1 RNA levels at the nadir (P < 0.0001) and inclusion of ritonavir or saquinavir versus indinavir in the starting regimen (P = 0.0313). Resistance to protease inhibitors was strongly associated with a lower response to treatment, as shown by HIV‐1 RNA load (P = 0.0001) and CD4 cell counts (P = 0.005). However, a linear increase in CD4 cell counts was maintained up to the end of follow‐up even in the protease inhibitor‐resistant population. Resistance to protease inhibitors develops in a relevant proportion of patients under long‐term triple‐drug therapy in clinical practice and is associated with virological treatment failure and limitation of CD4 cell increase. J. Med. Virol. 66:143–150, 2002. © 2002 Wiley‐Liss, Inc.
Hepatitis C virus NS4A and NS4B proteins suppress translation in vivo
Authors: Kato Jun , Kato Naoya , Yoshida Hideo , Ono‐Nita Suzane Kioko , Shiratori Yasushi , Omata Masao 
Published: August 2002

AbstractMany viruses can inhibit protein synthesis in their host cells by targeting translation (“translational shutoff”). There are few reports on the effects of hepatitis C virus (HCV) infection on protein synthesis, because of the lack of a reproducible tissue culture system for HCV. In this study, the influence of seven HCV proteins (core, NS2, NS3, NS4A, NS4B, NS5A, NS5B) on protein synthesis was examined using a reporter assay. In addition, it was determined whether the HCV proteins inhibit protein synthesis via transcription or translation using an RNase protection assay and the effect of HCV proteins on translation from the HCV internal ribosome entry site (IRES) was also examined using a bicistronic reporter. Of the seven HCV proteins, NS4A and NS4B proteins inhibited cellular protein synthesis by targeting the process of translation. They also inhibited translation from the HCV IRES. Moreover, NS4A protein, induced under the control of doxycycline, inhibited the proliferation of HeLa cells. In conclusion, HCV NS4A and NS4B proteins have an effect of translational inhibition. This novel function may be involved in HCV infection and help its survival in host cells. J. Med. Virol. 66:187–199, 2002. © 2002 Wiley‐Liss, Inc.
Effect of ethanol on the metabolism of primary astrocytes studied by 13C‐ and 31P‐NMR spectroscopy
Authors: Fonseca Luís L. , Alves Paula M. , Carrondo Manuel J.T. , Santos Helena 
Published: August 2002

AbstractNuclear magnetic resonance was used as the primary technique to investigate the effect of ethanol (40, 80, and 160 mM) on the levels of high‐energy phosphates, glycolytic flux, anaplerotic and oxidative fluxes to the tricarboxylic acid (TCA) cycle, the contribution of the pentose phosphate pathway (PPP), and the uptake and release of amino acids on primary cultures of rat astrocytes. On line 31P‐NMR spectroscopy showed that long‐term exposure to ethanol caused a drop in the levels of ATP and phosphocreatine. The ratio between the fluxes through the pyruvate dehydrogenase and pyruvate carboxylase reactions also decreased, whereas the glycolytic flux and the ratio between formation of lactate and glucose consumption increased when cells were exposed to acute doses of ethanol. Flux through the pentose phosphate pathway was not affected. The uptake of cysteine and the release of glutamine were stimulated by ethanol, whereas the release of methionine was inhibited. Moreover, the fractional enrichment in serine was enhanced. The changes in the amino acid metabolism are interpreted as a response to oxidative stress induced by ethanol. © 2001 Wiley‐Liss, Inc.
Retinoic acid increases proliferation rate of GL‐15 glioma cells, involving activation of STAT‐3 transcription factor
Authors: Paillaud E. , Costa S. , Fages C. , Plassat J.L. , Rochette‐Egly C. , Monville C. , Tardy M. 
Published: August 2002

AbstractThe molecular mechanisms underlying the heterogeneous effects of retinoic acid (RA) treatment on malignant glioma cells remain poorly understood. In this study, we present the first evidence of a functional role of the signal transduction factors (STATs) in RA‐induced proliferation, in a human glioblastoma GL‐15 cell line. We first observed that STAT‐3 was constitutively activated and present in the GL‐15 cell nuclei. We then showed that at low doses (0.01–1 μM) RA increased both the proliferation rate of GL‐15 cells and the phosphotyrosine (PY) activation of STAT‐3. This RA effect involved transcriptional processes and the transactivation of RA target genes, including RA receptors isoforms RARα2, ‐β2, and ‐γ2. At higher concentrations, however, RA (5–10 μM) inhibits GL‐15 proliferation, induces apoptosis, and fails to activate STAT‐3. An inhibitory effect on GL‐15 proliferation was also observed with the synthetic retinoids CD‐437 and CD‐2325, two structurally related RARγ agonists, which also fail to activate STAT‐3. In addition, the phorbol ester PMA, an inducer of GL‐15 differentiation, and staurosporine, a broad inhibitor of protein kinases, abrogate the stimulatory effects of RA at low concentrations. Together these observations suggest that, in GL‐15 cells, activation of STAT‐3 and cell proliferation share common mechanisms and that STAT transcription factors may be involved in a switch between proliferation, differentiation, and apoptosis. The proliferating effect observed at low doses of RA may be related to the failures in RA efficiency observed in clinical assays in relapsing malignant gliomas. Combining specific inhibitors of tyrosine kinases with RA might optimize the clinical outcome. © 2002 Wiley‐Liss, Inc.
Secreted phospholipase A2 potentiates glutamate‐induced calcium increase and cell death in primary neuronal cultures
Authors: DeCoster Mark A. , Lambeau Gerard , Lazdunski Michel , Bazan Nicolas G. 
Published: August 2002

AbstractSecreted phospholipases A2 (sPLA2s) modulate neuronal survival and neurotransmitter release. Here we show that sPLA2 (group III) synergistically increases glutamate‐induced cell death and intracellular calcium ([Ca2+]i) in cultured primary cortical and hippocampal neurons. Whereas 1 μM glutamate elicited transient [Ca2+]i increases in all neurons that recovered 66% to baseline, 25 ng/ml sPLA2 pretreatment resulted in sustained [Ca2+]i increases, with only 5% recovery. At 250 nM glutamate, 25% of neurons failed to respond, and the average recovery time was 101 ± 12 sec; sPLA2 increased recovery time to 158 ± 6 sec, and only 2% of cells failed to respond. Both the noncompetitive N‐methyl‐D‐aspartate (NMDA) receptor antagonist MK‐801 and the calcium‐channel blocker cobalt inhibited this effect. Experiments with the glutamate uptake inhibitor L‐trans‐pyrollidine‐2,4‐dicarboxylic acid (2.5 μM) indicated that glutamate uptake sites are not a likely modulation point by sPLA2, whereas arachidonic acid (AA) potentiated calcium responses to glutamate. Thus the enhancement of glutamate‐induced [Ca2+]i increases by sPLA2 may be due to modulation at NMDA receptors and/or calcium channels by AA. These results indicate that sPLA2 affects neuronal responses to both nontoxic (0.1–10 μM) and toxic (=25 μM) concentrations of glutamate, implicating this enzyme in neuronal functions in pathology. © 2002 Wiley‐Liss, Inc.
Nogos and the Nogo‐66 receptor: Factors inhibiting CNS neuron regeneration
Authors: Ng Cherry Ee Lin , Tang Bor Luen 
Published: August 2002

AbstractThe recently cloned gene Nogo, whose alternative splice products correspond to the antigenic target of the central nervous system (CNS) regeneration enhancing monoclonal antibody IN‐1, codes for membrane proteins enriched in brain, particularly in oligodendrocytes. The 66‐amino acid extracellular domain of Nogo (Nogo‐66) interacts with a high‐affinity receptor (NgR), a glycosylphosphatidylinositol (GPI)‐linked protein with multiple leucine‐rich repeats. The amino terminal cytoplasmic domain of Nogo appears to have a general cellular growth inhibitory effect. Nogo‐66, on the other hand, specifically retards neurite outgrowth and induces growth cone collapse, possibly through its interaction with NgR and as yet unidentified transmembrane coreceptors. Recent results also suggest that Nogo expression may induce apoptosis in tumor cells. Together, these proteins provide new molecular handles for the design of therapeutic interventions for CNS injuries and neurodegenerative diseases, as well as possible leads to anticancer strategies. © 2002 Wiley‐Liss, Inc.
Visual responses of neurons in the nucleus of the basal optic root to stationary stimuli in pigeons
Authors: Gu Yong , Wang Yuan , Wang Shu‐Rong 
Published: August 2002

AbstractThe nucleus of the basal optic root of the accessory optic system in pigeons is involved in generating optokinetic nystagmus, which stabilizes object images on the retina by compensatory eye movements. Previous studies have indicated that basal optic neurons are selective for the direction and velocity of motion. The present study shows that these optokinetic cells also respond to stationary stimuli and thereby could be categorized into three groups. The first group of cells (69.1%) responds to stationary gratings orthogonal to the preferred direction but not to gratings parallel to the preferred direction. They do not respond to stationary random‐dot patterns without any orientational cues. The second group of cells (7.4%) almost equally discharges a series of bursts in response to stationary gratings with any orientations and to random‐dot patterns as well. The third group of cells (23.5%) is responsive to motion but not to stationary gratings and random‐dot patterns. The receptive field of basal optic cells is composed of an excitatory field and an inhibitory field, both of which overlap or occupy different regions in the visual field. The aforementioned properties may be attributed to the excitatory receptive field, whereas the inhibitory receptive field is functional when visual stimuli are moving in the direction opposite to the preferred direction of basal optic cells. The functional significance of visual responses of optokinetic neurons to stationary patterns is discussed. © 2002 Wiley‐Liss, Inc.
High‐density microarray analysis of hippocampal gene expression following experimental brain injury
Authors: Matzilevich David A. , Rall Jason M. , Moore Anthony N. , Grill Raymond J. , Dash Pramod K. 
Published: August 2002

AbstractBehavioral, biophysical, and pharmacological studies have implicated the hippocampus in the formation and storage of spatial memory. Traumatic brain injury (TBI) often causes spatial memory deficits, which are thought to arise from the death as well as the dysfunction of hippocampal neurons. Cell death and dysfunction are commonly associated with and often caused by altered expression of specific genes. The identification of the genes involved in these processes, as well as those participating in postinjury cellular repair and plasticity, is important for the development of mechanism‐based therapies. To monitor the expression levels of a large number of genes and to identify genes not previously implicated in TBI pathophysiology, a high‐density oligonucleotide array containing 8,800 genes was interrogated. RNA samples were prepared from ipsilateral hippocampi 3 hr and 24 hr following lateral cortical impact injury and compared to samples from sham‐operated controls. Cluster analysis was employed using statistical algorithms to arrange the genes according to similarity in patterns of expression. The study indicates that the genomic response to TBI is complex, affecting approximately 6% (at the time points examined) of the total number of genes examined. The identity of the genes revealed that TBI affects many aspects of cell physiology, including oxidative stress, metabolism, inflammation, structural changes, and cellular signaling. The analysis revealed genes whose expression levels have been reported to be altered in response to injury as well as several genes not previously implicated in TBI pathophysiology. © 2002 Wiley‐Liss, Inc.
Insulin‐like growth factor binding proteins‐1 and ‐2 differentially inhibit rat oligodendrocyte precursor cell survival and differentiation in vitro
Authors: Kühl Nicole M. , De Keyser Jacques , De Vries Hans , Hoekstra Dick 
Published: August 2002

AbstractInsulin‐like growth factor‐1 (IGF‐1) is a growth and survival factor for oligodendrocyte lineage cells and induces myelination. Its actions are modulated by IGF binding proteins (IGFBPs) that are present in the extracellular fluids or on the cell surface. Additionally, IGFBPs are also known to exert actions that are independent of IGF‐1. We studied whether IGF‐binding proteins (IGFBPs)‐1 and ‐2 modulate rat oligodendrocyte precursor (O2A) cell survival and differentiation in vitro both in the absence and presence of exogenously added IGF‐1. The data reveal that IGFBP‐1 and ‐2 reduced O2A cell survival in the absence and presence of exogenously added IGF‐1. The effects of IGFBP‐1 on cell survival in the presence of exogenously added IGF‐1 were IGF‐1‐dependent, whereas IGFBP‐2 displayed both IGF‐1‐dependent and IGF‐1‐independent effects. Furthermore, IGFBP‐1 and ‐2 inhibited O2A cell differentiation in the presence of IGF‐1 as reflected by decreased expression levels of two myelin proteins, CNPase (2′,3′‐cyclic nucleotide 3′‐phosphohydrolase) and MAG (myelin associated glycoprotein). Analysis of medium samples revealed that O2A cells do not secrete proteases that degrade these IGFBPs. Taken together the data show that IGFBP‐1 and ‐2 are negative effectors of oligodendrocyte survival and differentiation. Accordingly, the role of IGFBPs should be explicitly taken into account when investigating IGF‐1 effects on oligodendrocytes, especially in the context of therapeutic purposes. © 2002 Wiley‐Liss, Inc.