bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pathophysiology of Stroke in Sickle Cell Disease
Authors: HILLERY CHERYL A. , PANEPINTO JULIE A. 
Published: October 2004

ABSTRACTStroke affects both motor and cognitive function in patients with sickle cell disease (SCD). Symptomatic stroke is associated with intimal disease of the large cerebral arteries. Silent stroke, defined as cerebral infarction in the absence of overt clinical neurologic symptoms, is often due to microinfarcts suggestive of microvascular disease. While the natural history of stroke in SCD is well described, the pathophysiology remains poorly understood and probably varies with the site of vascular injury. Increased red cell adhesion, oxidative injury of the vessel wall, inflammation, abnormal vasomotor tone regulation, and increased activity of the coagulation system all may contribute to cerebral vasopathology in SCD.
Sickle Red Cell Microrheology and Sickle Blood Rheology
Authors: BALLAS SAMIR K. , MOHANDAS NARLA 
Published: October 2004

ABSTRACTThe hallmark of the phenotypic expression of sickle cell disease is the remarkable degree of heterogeneity in the clinical manifestations. They vary latitudinally among patients and longitudinally in the same patient. The pathogenesis of sickle cell anemia centers on the sequence of events that occur between polymerization of deoxy hemoglobin S and increased red cell destruction, vasoocclusion, and end organ damage. Cellular dehydration, changes in sickle red blood cell rheology, adhesion of sickle red cells to vascular endothelium, inflammatory response, and tissue injury are some of the factors that contribute to hemolytic anemia, vasoocclusion, and eventual multiorgan damage. The focus of this review is on the rheology of sickle blood and microrheology of sickle RBC. Determinants of sickle RBC rheology and the factors that modulate its severity are discussed.
Reconstructing biological networks using conditional correlation analysis
Authors: Rice John Jeremy , Tu Yuhai , Stolovitzky Gustavo 
Published: October 2004

AbstractMotivation: One of the present challenges in biological research is the organization of the data originating from high-throughput technologies. One way in which this information can be organized is in the form of networks of influences, physical or statistical, between cellular components. We propose an experimental method for probing biological networks, analyzing the resulting data and reconstructing the network architecture.Methods: We use networks of known topology consisting of nodes (genes), directed edges (gene–gene interactions) and a dynamics for the genes' mRNA concentrations in terms of the gene–gene interactions. We proposed a network reconstruction algorithm based on the conditional correlation of the mRNA equilibrium concentration between two genes given that one of them was knocked down. Using simulated gene expression data on networks of known connectivity, we investigated how the reconstruction error is affected by noise, network topology, size, sparseness and dynamic parameters.Results: Errors arise from correlation between nodes connected through intermediate nodes (false positives) and when the correlation between two directly connected nodes is obscured by noise, non-linearity or multiple inputs to the target node (false negatives). Two critical components of the method are as follows: (1) the choice of an optimal correlation threshold for predicting connections and (2) the reduction of errors arising from indirect connections (for which a novel algorithm is proposed). With these improvements, we can reconstruct networks with the topology of the transcriptional regulatory network in Escherichia coli with a reasonably low error rate.Contact: gustavo@us.ibm.comSupplementary information: Available from our website: www.research.ibm.com/FunGen
Respiratory and cardiovascular function at rest and during exercise testing in a
healthy working population: effects of outdoor traffic air pollution
Authors: Volpino P. , Tomei F. , La Valle C. , Tomao E. , Rosati M. V. , Ciarrocca M. , De Sio S. , Cangemi B. , Vigliarolo R. , Fedele F. 
Published: October 2004

Abstract
Background
There is controversy regarding long-term adverse effects of urban pollutants in urban workers.
Aim
The aim of this study was to evaluate the effects of urban pollutants on respiratory and cardiovascular function in exposed traffic policemen compared to a control group.
Methods
Sixty-eight traffic policemen and 62 controls (all male) were investigated at rest and during symptom-limited incremental exercise test (performed with a cycle ergometer). The data were statistically evaluated.
Results
There were no significant differences in the mean values of resting ventilatory capacity, the forced spirometric test, or in blood gas parameters between the groups. The traffic exposed group demonstrated a number of significant changes in cardiorespiratory measures on exercise testing. Twenty-six traffic policemen and none of the controls experienced exercise-induced ECG abnormalities, hypertension or oxyhaemoglobin desaturation; 80% of the 26 had resting PaO2 values <80 mmHg.
Conclusion
The findings suggest that chronic occupational exposure to urban pollutants reduces resistance to physical effort and increases the risk of cardiovascular and respiratory changes including slight hypoxemia.
The Search for Genes Contributing to the Low Level of Response to Alcohol: Patterns of Findings Across Studies
Authors: Schuckit Marc A. , Smith Tom L. , Kalmijn Jelger 
Published: October 2004

Background: Alcoholism is a complex genetically influenced disorder in which multiple phenotypes [e.g., disinhibition, alcohol‐metabolizing patterns, and the low level of response (LR) to alcohol] contribute to the risk. A low LR to alcohol is one of the more thoroughly studied risk phenotypes; data indicate that LR relates to the risk status, predicts future alcoholism, and has a heritability as high as 60%. This article reviews data from animal and human studies regarding the LR to alcohol, searching for a convergence of results that might lead to the identification of relevant genes.Methods: A literature search was performed regarding animal and human genetic studies focusing on genes that might affect the LR to alcohol as a risk factor for alcoholism. The goal was to synthesize these results and highlight potential patterns.Results: Focusing on both genetic linkage and association studies, a number of chromosomal regions and genes potentially relevant to findings across two or more sources were identified. The genes of potential interest fell into several categories, including second‐messenger systems (e.g., G proteins, adenylyl cyclase, and protein kinases); neurotransmitters or drug‐related receptors (e.g., γ‐aminobutyric acid‐A, glutamate, serotonin, and cannabinoid and opioid receptors); genes that affect alcohol metabolism; and genes that might relate to an overlap in the risk for alcoholism and some psychiatric conditions (e.g., catechol‐O‐methyltransferase regarding schizophrenia and bipolar disorder).Conclusions: The review identifies several genes that may contribute to a low LR to alcohol and, thus, to an increased risk for alcohol use disorders. The chromosomal regions and genes highlighted here may form the basis for more focused genetic studies of alcohol use disorders, with the goals of developing more specific and effective prevention and treatment approaches.
National and State Estimates of the Mean Ethanol Content of Beer Sold in the US and Their Impact on Per Capita Consumption Estimates: 1988 to 2001
Authors: Kerr William C. , Brown Stephan , Greenfield Thomas K. 
Published: October 2004

Background: The average ethanol content of the beer sold in the US is a key factor in determining the per capita consumption of ethanol, the standard measure of alcohol use in aggregate‐level research. To address the lack of empirically based estimates of beer ethanol content, we have calculated national estimates for the years 1988 to 2001 and state‐specific estimates for 1993 to 2001.Methods: These estimates are based on the ethanol content by volume of leading brands in each year, the national market share of each leading brand by type, and state‐specific market shares of each beer type.Results: The national mean ethanol content of beer was higher than the 4.5% figure typically used, ranging from 4.58% in 1993 to 4.75% in 1996. State‐specific mean ethanol content estimates were also found to vary by state and over time. Application of mean ethanol content estimates to the per capita consumption of beer led to higher consumption estimates than those with the 4.5% conversion. For example, in 2000, the national estimate indicates that nearly 10 more drinks (containing 0.6 oz of ethanol) were consumed per person aged 14 years and older during that year.Conclusions: This may indicate that a larger than previously estimated share of the alcohol consumed in the US is in the form of beer. However, the results also indicate that empirically based estimates of wine and spirits mean that ethanol content may modify their consumption estimates as well.
Inward Rectifier Potassium Channels in the Basilar Artery During Chronic Alcohol Consumption
Authors: Sun Hong , Fang Qin , Mayhan William G. 
Published: October 2004

Background: The goals of this study were to determine whether chronic alcohol consumption alters potassium channel–mediated reactivity in the basilar artery and to determine a potential mechanism that might account for the effects of alcohol on the basilar artery.Methods: Sprague‐Dawley rats were fed liquid diets with or without alcohol for 2 to 3 months. We measured diameter of the basilar artery in response to potassium channel inhibitors and activators. Protein level of inward rectifier potassium channel subunit Kir2.1 in the basilar artery was determined by Western blot.Results: Topical application of glibenclamide (1 and 10 μM) significantly constricted the basilar artery at high dose; iberiotoxin (10 and 100 nM), 4‐AP (0.1 and 1 mM), and BaCl2 (1 and 10 μM) produced dose‐related constriction in both non–alcohol‐fed and alcohol‐fed rats. However, the magnitude of constriction in response to BaCl2 was significantly less in alcohol‐fed rats compared with non–alcohol‐fed rats. Topical application of KCl (1 and 3 mM), cromakalim (0.1 and 0.3 μM), and NS1619 (10 and 30 μM) induced dose‐related dilation in non–alcohol‐fed and alcohol‐fed rats. However, the magnitude of vasodilation in response to KCl was significantly less in alcohol‐fed rats compared with non–alcohol‐fed rats. In addition, Kir2.1 protein level in the basilar artery was significantly reduced in alcohol‐fed compared with non–alcohol‐fed rats.Conclusions: These findings suggest that chronic alcohol consumption reduces expression of inward rectifier potassium channels and inhibits KIR channel–mediated dilation in the basilar artery.
Predictors of High Ethanol Consumption in RIIβ Knock‐Out Mice: Assessment of Anxiety and Ethanol‐Induced Sedation
Authors: Fee Jon R. , Sparta Dennis R. , Knapp Darin J. , Breese George R. , Picker Mitchell J. , Thiele Todd E. 
Published: October 2004

Background: Genetic and pharmacological evidence suggests that the cyclic adenosine monophosphate–dependent protein kinase A pathway modulates neurobiological responses to ethanol. Mutant mice lacking the RIIβ subunit of protein kinase A (RIIβ−/−) are resistant to ethanol‐induced sedation and drink significantly more ethanol than littermate wild‐type mice (RIIβ+/+). We determined whether high ethanol intake by the RIIβ−/− mice on alternate genetic backgrounds is reliably predicted by high basal levels of anxiety or resistance to the sedative effects of ethanol.Methods: Two‐bottle choice procedures and a battery of behavioral tests (elevated plus maze, open‐field activity, and zero maze) were used to assess voluntary ethanol consumption and basal levels of anxiety in RIIβ−/− and RIIβ+/+ mice on either a C57BL/6J or a 129/SvEv × C57BL/6J genetic background. Additionally, ethanol‐induced sedation and blood ethanol levels were determined in RIIβ−/− and RIIβ+/+ mice after intraperitoneal injection of ethanol (3.8 g/kg).Results: RIIβ−/− mice on both genetic backgrounds consumed more ethanol and had a greater preference for ethanol relative to RIIβ+/+ mice. However, RIIβ−/− mice showed reduced basal levels of anxiety when maintained on the C57BL/6J background but showed increased anxiety when maintained on the 129/SvEv × C57BL/6J background. Consistent with prior research, RIIβ−/− mice were resistant to the sedative effects of ethanol, regardless of the genetic background. Finally, RIIβ−/− and RIIβ+/+ mice showed similar blood ethanol levels.Conclusions: These results indicate that high ethanol consumption is associated with resistance to the sedative effects of ethanol but that basal levels of anxiety, as well as ethanol metabolism, do not reliably predict high ethanol drinking by RIIβ−/− mice.
Blood Oxygen Level Dependent Response and Spatial Working Memory in Adolescents With Alcohol Use Disorders
Authors: Tapert Susan F. , Schweinsburg Alecia D. , Barlett Valerie C. , Brown Sandra A. , Frank Lawrence R. , Brown Gregory G. , Meloy M J. 
Published: October 2004

Background: Previous studies have suggested neural disruption and reorganization in young and older adults with alcohol use disorders (AUD). However, it remains unclear at what age and when in the progression of AUD changes in brain functioning might occur.Methods: Alcohol use disordered (n= 15) and nonabusing (n= 19) boys and girls aged 15 to 17 were recruited from local high schools. Functional magnetic resonance imaging data were collected after a minimum of 5 days’ abstinence as participants performed spatial working memory and simple motor tasks.Results: Adolescents with AUD showed greater brain response to the spatial working memory task in bilateral parietal cortices and diminished response in other regions, including the left precentral gyrus and bilateral cerebellar areas (clusters ≥943 μl; p < 0.05), although groups did not differ on behavioral measures of task performance. No brain response differences were observed during a simple finger‐tapping task. The degree of abnormality was greater for teens who reported experiencing more withdrawal or hangover symptoms and who consumed more alcohol.Conclusions: Adolescents with AUD show abnormalities in brain response to a spatial working memory task, despite adequate performance, suggesting that subtle neuronal reorganization may occur early in the course of AUD.
Rapid and Chronic: Two Distinct Forms of Ethanol Tolerance in Drosophila
Authors: Berger Karen H. , Heberlein Ulrike , Moore Monica S. 
Published: October 2004

Background: Ethanol tolerance, defined as a reduction in the intensity of the effects of ethanol upon continuous or repeated exposure, is a hallmark of alcoholism. Tolerance may develop at the cellular or neural systems levels. The molecular changes underlying ethanol tolerance are not well understood. We therefore explored the utility of Drosophila, with its accessibility to genetic, molecular, and behavioral analyses, as a model organism to study tolerance development in response to different ethanol‐exposure regimens.Methods: We describe a new assay that quantifies recovery from ethanol intoxication in Drosophila. Using this recovery assay, we define ethanol pre‐exposure paradigms that lead to the development of tolerance. We also use the inebriometer, an assay that measures the onset of intoxication, to study the effects of pharmacological and genetic manipulations on tolerance development.Results: We show that flies develop different forms of ethanol tolerance: rapid tolerance, induced by a single short exposure to a high concentration of ethanol, and chronic tolerance, elicited by prolonged exposure to a low concentration of the drug. Neither rapid nor chronic tolerance involves changes in ethanol pharmacokinetics, implying that they represent functional rather than dispositional tolerance. Chronic and rapid tolerance can be distinguished mechanistically: chronic tolerance is disrupted by treatment with the protein synthesis inhibitor cycloheximide, whereas rapid tolerance is resistant to this treatment. Furthermore, rapid and chronic tolerance rely on distinct genetic pathways: a mutant defective for octopamine biosynthesis shows reduced rapid tolerance but normal chronic tolerance.Conclusions: Flies, like mammals, develop tolerance in response to different ethanol‐exposure regimens, and this tolerance affects both the onset of and the recovery from acute intoxication. Two forms of tolerance, rapid and chronic, are mechanistically distinct, because they can be dissociated genetically and pharmacologically.
Genetic and Environmental Effects on Conduct Disorder and Alcohol Dependence Symptoms and Their Covariation at Age 14
Authors: Rose Richard J. , Dick Danielle M. , Viken Richard J. , Pulkkinen Lea , Kaprio Jaakko 
Published: October 2004

Background: Alcohol misuse and conduct disorder (CD) are strongly associated in adolescents. Is their association due to shared genetic and environmental liabilities? We addressed that question with data obtained from structured interviews of 14‐year‐old Finnish twins.Methods: A total of 1854 twins completed face‐to‐face interviews. Univariate models, allowing for sex limitation, were fit to symptom counts for Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised diagnoses of CD and alcoholism to examine their genetic and environmental influences. Then, bivariate models evaluated the extent to which genetic and environmental influences contributed to the covariation between symptom counts for the two disorders.Results: A total of 822 twins (44% of the sample) reported one or more symptoms of CD; alcohol dependence symptoms were much less common, reported by only 12%. The correlation between the two symptom counts was 0.50. Models fit to the twin data demonstrated that CD symptoms were under significant genetic influence in both boys and girls, although those influences were predominantly sex specific. In contrast, alcohol dependence symptoms were, at this age, under sex‐specific effects of common environments, with no evidence of genetic influences. Accordingly, the substantial covariation between alcohol dependence symptoms and those of CD was attributed entirely to shared environmental effects.Conclusions: At age 14, genetic influences on alcohol dependence symptoms are negligible, and the correlated liabilities between these symptoms and those of CD are to be found in environmental factors that are common to both.
The University of California, San Francisco Family Alcoholism Study. I. Design, Methods, and Demographics
Authors: Vieten Cassandra , Seaton Kimberly L. , Feiler Heidid S. , Wilhelmsen Kirk C. 
Published: October 2004

Background: The University of California, San Francisco (UCSF) Family Alcoholism Study is a project designed to identify genetic loci that influence susceptibility to alcohol dependence and related phenotypes. Evidence supports a substantial genetic contribution to alcoholism susceptibility. However, the genetic epidemiology of alcoholism is complex, and its clinical manifestation is heterogeneous, making phenotype definition and demonstration of linkage difficult. Despite these challenges, some progress has been made toward identifying genes.Methods: The UCSF Family Alcoholism Study used a small family design, focusing primarily on sibling pairs and parent‐child trios for linkage and association studies. Alcoholism‐related phenotypes were assessed through interview and self‐report questionnaires, with a focus on unidimensional and subphenotypical traits. Data‐driven approaches to determining the most promising phenotypes for genetic analysis are being used. Both genome‐wide scan and candidate gene approaches were used.Results: The study enrolled 2154 individuals from 970 families from December 1995 through January 2003. Test‐retest and interrater reliability for clinical data are very good, and power estimates suggest that this study will have adequate power by linkage analysis to detect loci with moderate effects. Design, methods, and sample demographics of the UCSF Family Study are presented, along with intrafamilial correlations for primary diagnostic phenotypes.Conclusions: Plans for genetic analysis, novel approaches to phenotype refinement, and the implications of ascertainment bias for heritability estimates are discussed.
Intermittent Ethanol Exposure in Adolescent Rats: Dose‐Dependent Impairments in Trace Conditioning
Authors: Yttri Eric A. , Burk Joshua A. , Hunt Pamela S. 
Published: October 2004

Background: Recent studies have revealed that the adolescent brain may be especially vulnerable to ethanol‐induced toxicity. Corticolimbic regions are more severely damaged following ethanol exposure during adolescence than during adulthood. The consequences of adolescent ethanol exposure on cognition however, have only recently begun to be explored.Methods: Male and female rats were administered 0, 1.5, 2.5 or 4.5 g/kg ethanol (20% v/v) by acute intragastric gavage during adolescence (postnatal days [PD] 28, 30, 32 and 34). On PD 40, half of the subjects in each dose group were given 5 pairings of a 10‐sec flashing light (CS; conditioned stimulus) immediately followed by mild footshock (US; unconditioned stimulus), a procedure known as delay conditioning. The other half were also given 5 CS‐US pairings, but the US was presented 10 sec after CS offset, a procedure known as trace conditioning. All subjects were tested for CS‐elicited freezing 24 h later.Results: There was no effect of adolescent ethanol exposure on delay conditioned responding, with all subjects demonstrating comparable levels of CS‐elicited freezing. In contrast, the amount of freezing in the trace conditioned subjects was negatively correlated with prior ethanol dose. Specifically, exposure to 2.5 or 4.5 g/kg during adolescence resulted in a deficit in trace conditioned responding.Conclusions: These data indicate that intermittent exposure to ethanol during adolescence results in impairment in hippocampal‐dependent trace conditioning that persists beyond the period of ethanol exposure. Delay conditioning was unaffected by prior ethanol treatment, indicating that there was no difficulty in detecting the CS or US, or in the ability to engage in freezing behavior. These results suggest that the adolescent brain may be particularly vulnerable to the effects of repeated exposure to ethanol that can have consequences for nonspatial, hippocampal‐dependent cognitive abilities.
Use of Phenylboronic Acids to Investigate Boron Function in Plants. Possible Role of Boron in Transvacuolar Cytoplasmic Strands and Cell-to-Wall Adhesion
Authors: Bassil Elias , Hu Hening , Brown Patrick H. 
Published: October 2004

Abstract
The only defined physiological role of boron in plants is as a cross-linking molecule involving reversible covalent bonds with cis-diols on either side of borate. Boronic acids, which form the same reversible bonds with cis-diols but cannot cross-link two molecules, were used to selectively disrupt boron function in plants. In cultured tobacco (Nicotiana tabacum cv BY-2) cells, addition of boronic acids caused the disruption of cytoplasmic strands and cell-to-cell wall detachment. The effect of the boronic acids could be relieved by the addition of boron-complexing sugars and was proportional to the boronic acid-binding strength of the sugar. Experiments with germinating petunia (Petunia hybrida) pollen and boronate-affinity chromatography showed that boronic acids and boron compete for the same binding sites. The boronic acids appear to specifically disrupt or prevent borate-dependent cross-links important for the structural integrity of the cell, including the organization of transvacuolar cytoplasmic strands. Boron likely plays a structural role in the plant cytoskeleton. We conclude that boronic acids can be used to rapidly and reversibly induce boron deficiency-like responses and therefore are useful tools for investigating boron function in plants.