bluuebunny/crossref_metadata_2025 huggingface dataset:
Privatization and Strategic Monitoring with Gaussian Priors
Authors: Disney Richard , Ellis Christopher J. , Nomer Bulent
Published: May 2005

This article describes the sale and optimal regulation of a sequence of public utilities, where monitoring of regulatory compliance is costly. The government is concerned with the revenue raised by successive privatizations as well as the standard objective of efficiency in production. The costs of monitoring are private information to the government. At each stage in the sequence of privatizations, the public Bayes updates its distribution of posterior beliefs over the government’s regulatory enforcement strategy. The government knows that this “learning” is taking place and chooses the time path of monitoring levels accordingly.
Life-threatening nonspherocytic hemolytic anemia in a patient with a null mutation in the PKLR gene and no compensatory PKM gene expression
Authors: Diez Amalia , Gilsanz Florinda , Martinez Joaquin , Pérez-Benavente Susana , Meza Néstor W. , Bautista José M.
Published: May 2005

Human erythrocyte R-type pyruvate kinase (RPK) deficiency is an autosomal recessive disorder produced by mutations in the PKLR gene, causing chronic nonspherocytic hemolytic anemia. Survival of patients with severe RPK deficiency has been associated with compensatory expression in red blood cells (RBCs) of M2PK, an isoenzyme showing wide tissue distribution. We describe a novel homozygous null mutation of the PKLR gene found in a girl with a prenatal diagnosis of PK deficiency. The mutant PK gene revealed an 11-nucleotide (nt) duplication at exon 8, causing frameshift of the PKLR transcript, predicting a truncated protein inferred to have no catalytic activity. Western blot analysis and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) detected no M2PK expression in the peripheral blood red cell fraction. The expression of mutant RPK mRNA in the RBCs was almost 6 times higher than that detected in a control patient with hereditary spherocytosis. This molecular phenotypic analysis of the null mutation in the PKLR gene provides evidence for a lack of M2PK in the mature RBCs of this patient and suggests that normal red cell functions and survival are achieved through a population of young erythroid cells released into the circulation in response to anemia. (Blood. 2005;106:1851-1856)
Guanylic nucleotide starvation affects Saccharomyces cerevisiae mother-daughter separation and may be a signal for entry into quiescence
Authors: Sagot Isabelle , Schaeffer Jacques , Daignan-Fornier Bertrand
Published: May 2005

Background

Guanylic nucleotides are both macromolecules constituents and crucial regulators for a variety of cellular processes. Therefore, their intracellular concentration must be strictly controlled. Consistently both yeast and mammalian cells tightly correlate the transcription of genes encoding enzymes critical for guanylic nucleotides biosynthesis with the proliferation state of the cell population.

Results

To gain insight into the molecular relationships connecting intracellular guanylic nucleotide levels and cellular proliferation, we have studied the consequences of guanylic nucleotide limitation on Saccharomyces cerevisiae cell cycle progression. We first utilized mycophenolic acid, an immunosuppressive drug that specifically inhibits inosine monophosphate dehydrogenase, the enzyme catalyzing the first committed step in de novo GMP biosynthesis. To approach this system physiologically, we next developed yeast mutants for which the intracellular guanylic nucleotide pools can be modulated through changes of growth conditions. In both the pharmacological and genetic approaches, we found that guanylic nucleotide limitation generated a mother-daughter separation defect, characterized by cells with two unseparated daughters. We then showed that this separation defect resulted from cell wall perturbations but not from impaired cytokinesis. Importantly, cells with similar separation defects were found in a wild type untreated yeast population entering quiescence upon nutrient limitation.

Conclusion

Our results demonstrate that guanylic nucleotide limitation slows budding yeast cell cycle progression, with a severe pause in telophase. At the cellular level, guanylic nucleotide limitation causes the emergence of cells with two unseparated daughters. By fluorescence and electron microscopy, we demonstrate that this phenotype arises from defects in cell wall partition between mother and daughter cells. Because cells with two unseparated daughters are also observed in a wild type population entering quiescence, our results reinforce the hypothesis that guanylic nucleotide intracellular pools contribute to a signal regulating both cell proliferation and entry into quiescence.
PathwayVoyager: pathway mapping using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database
Authors: Altermann Eric , Klaenhammer Todd R
Published: May 2005

Background

Equally important and challenging as genome annotation, is the subsequent classification of predicted genes into their respective pathways. The Kyoto Encyclopedia of Genes and Genomes (KEGG) represents a database consisting of known genes and their respective biochemical functionalities. Although accessible online, analyses of multiple genes are time consuming and are not suitable for analyzing data sets that are proprietary.

Results

Presented here is a new software solution that utilizes the KEGG online database for pathway mapping of partial and whole prokaryotic genomes. PathwayVoyager retrieves user-defined subsets of the KEGG database and stores the data as local, blast-formatted databases. Previously selected datasets can be re-used, reducing run-time significantly. Whole or partial genomes can be automatically analyzed using NCBI's BlastP algorithm and ORFs with similarities below the user-defined threshold will be marked on pathway maps. Multiple gene hits are sorted by similarity. Since no sequence information is transmitted over the Internet, PathwayVoyager is an ideal solution for pathway mapping and reconstruction of confidential DNA sequence data.

Conclusion

PathwayVoyager represents an alternative approach to many already existing, more complex pathway reconstructions software solutions. This software does not require any dedicated hardware or software and is flexible and straightforward to use. It is ideally suited for environments where analyses on variable datasets are desired.
Regulation of skeletal muscle fiber type and slow myosin heavy chain 2 gene expression by inositol trisphosphate receptor 1
Authors: Jordan Theresa , Jiang Hongbin , Li Hui , DiMario Joseph X.
Published: May 2005

Innervation-dependent signaling cascades that control activation of downstream transcription factors regulate expression of skeletal muscle fiber type-specific genes. Many of the innervation-regulated signaling cascades in skeletal muscle are dependent on intracellular calcium and the mechanisms by which calcium is released from the sarcoplasmic reticulum (SR). We report that the inositol trisphosphate receptor 1 (IP3R1), responsible for calcium release from the SR as a slow wave, was more abundant in fast contracting compared to slow contracting avian muscle fibers. Furthermore, inhibition of IP3R1 activity by 2-aminoethoxydiphenylborate (2-APB) and xestospongin D induced a fiber type transition and expression of the slow myosin heavy chain 2 (slow MyHC2) gene in innervated fast muscle fibers. Activation of the slow MyHC2 promoter by IP3R1 inhibition was accompanied by a reduction in protein kinase C activity. In addition, inhibition of IP3R1 activity resulted in a reduction of nuclear factor of activated T cells (NFAT)-dependent transcription and nuclear localization, indicating that IP3R1 activity regulated NFAT transcription factor activity in skeletal muscle fibers. Myocyte enhancer factor 2 (MEF2)-dependent transcriptional activity was increased by innervation, but unaffected by IP3R1 activity. The results indicate that IP3R1 activity regulates muscle fiber type-specific gene expression in innervated muscle fibers.
Expression of truncated latent TGF-β-binding protein modulates TGF-β signaling
Authors: Mazzieri Roberta , Jurukovski Vladimir , Obata Hiroto , Sung Joanne , Platt Alec , Annes Eric , Karaman-Jurukovska Nevena , Gleizes Pierre-Emmanuel , Rifkin Daniel B.
Published: May 2005

Transforming growth factor-β is released from most cells as an inactive complex consisting of transforming growth factor-β, the transforming growth factor-β propeptide and the latent transforming growth factor-β-binding protein. We studied the role of latent transforming growth factor-β-binding protein in modulating transforming growth factor-β availability by generating transgenic mice that express a truncated form of latent transforming growth factor-β-binding protein-1 that binds to transforming growth factor-β but is missing the known N- and C-terminal matrix-binding sequences. As transforming growth factor-β is an inhibitor of keratinocyte proliferation and is involved in the control of hair cycling, we over-expressed the mutated form of latent transforming growth factor-β-binding protein under the control of the keratin 14-promoter. Transgenic animals displayed a hair phenotype due to a reduction in keratinocyte proliferation, an abbreviated growth phase and an early initiation of the involution (catagen) phase of the hair cycle. This phenotype appears to result from excess active transforming growth factor-β, as enhanced numbers of pSmad2/3-positive nuclei are observed in transgenic animal skin. These data suggest that the truncated form of latent transforming growth factor-β-binding protein-1 competes with wild-type latent transforming growth factor-β-binding protein for binding to latent transforming growth factor-β, resulting in latent transforming growth factor-β complexes that fail to be targeted correctly in the extracellular matrix. The mis-localization of the transforming growth factor-β results in inappropriate activation and premature initiation of catagen, thereby illustrating the significance of latent transforming growth factor-β-binding protein interaction with transforming growth factor-β in the targeting and activation of latent transforming growth factor-β in addition to previously reported effects on small latent complex secretion.
Nelarabine: A Nucleoside Analog with Efficacy in T-Cell and other Leukemias
Authors: Kisor David F
Published: May 2005

OBJECTIVE:

To present the pharmacology and pharmacokinetics of nelarabine, 9-β-D-arabinofuranosylguanine (ara-G) and intraleukemic cellular pharmacokinetics of 9-β-D-arabinofuranosylguanine triphosphate (ara-GTP) generated from the administration of nelarabine, and clinical and safety information relative to nelarabine use in the treatment of hematologic malignancies.

DATA SOURCES:

MEDLINE (1966—December 2004) was searched using the English-language key terms 2-amino-6-methoxypurine arabinoside, 506U78, and nelarabine. Data were also obtained from published abstracts.

STUDY SELECTION AND DATA EXTRACTION:

Clinical studies evaluating the pharmacokinetics of nelarabine, ara-G, and cellular ara-GTP and use of nelarabine, alone or in combination with other agents for the treatment of hematologic malignancies, were included in this review.

DATA SYNTHESIS:

Nelarabine is the water-soluble, 6-methoxy analog of 9-β-D-ara-G. Nelarabine is readily converted to ara-G by endogenous adenosine deaminase. The half-life of nelarabine is approximately 15 minutes compared with 2–4 hours for ara-G. The clearance of ara-G is higher in children than in adults (0.312 vs 0.213 L × h−1 × kg−1). Intracellular ara-GTP elimination is slow relative to nelarabine and ara-G. In pediatric and adult patients, neurologic toxicity is dose limiting. Severe myelosuppression was not consistently observed. Major responses were seen in patients with T-cell malignancies. Patients who responded had significantly higher intracellular ara-GTP concentrations compared with those who did not respond.

CONCLUSIONS:

Nelarabine is an effective ara-G prodrug. Nelarabine has significant activity against malignant T-cells and appears to be an important addition to treatments of various leukemias.
Impact of Nonsteroidal Antiinflammatory Drugs on the Cardioprotective Effects of Aspirin
Authors: Corman Shelby L , Fedutes Bethany A , Ansani Nicole T
Published: May 2005

OBJECTIVE:

To examine the evidence of a pharmacodynamic interaction between aspirin and nonsteroidal antiinflammatory drugs (NSAIDs); specifically, to determine whether a deleterious relationship exists with respect to the cardioprotective effects of aspirin.

DATA SOURCES:

Primary articles were identified by a MEDLINE search (1966—May 2004). Search terms included aspirin, nonsteroidal antiinflammatory drug, drug interaction, mortality, myocardial infarction, and stroke.

STUDY SELECTION AND DATA EXTRACTION:

All prospective and retrospective studies conducted in human subjects and investigating the potential interaction between aspirin and NSAIDs were included.

DATA SYNTHESIS:

Several controlled pharmacodynamic studies indicate that the sustained inhibition of cyclooxygenase activity by aspirin is blunted in the presence of some NSAIDs. While these data are fairly consistent, they are limited in that they rely on surrogate markers and not clinical outcomes. Observational studies have shown conflicting results regarding the effect of combination NSAID and aspirin therapy on mortality risk and incidence of myocardial infarction.

CONCLUSIONS:

Pharmacodynamic data indicating an interaction between aspirin and NSAIDs have not translated to a consistent clinical effect in observational studies. In the absence of a randomized, controlled, clinical outcomes study, there is insufficient evidence to dictate a change in therapy.
Atomoxetine Ingestions in Children: A Report from Poison Centers
Authors: Spiller Henry A , Lintner Chris P , Winter Mark L
Published: May 2005

BACKGROUND:

Atomoxetine uses a novel nonstimulant approach to the treatment of attention deficit hyperactivity disorder. There is limited information on overdose of atomoxetine in children or adults.

OBJECTIVE:

To provide information on atomoxetine in overdose.

METHODS:

Case series were conducted at 3 regional poison centers for atomoxetine ingestion in children (age ⩽17 y). Exclusion criteria were polypharmacy or lack of follow-up.

RESULTS:

Forty patients were included (25 boys; 63%) in the study. The mean ± SD age was 6.1 ± 4.9 years (range 9 mo–17 y). Twenty-five patients were managed at home, 14 in hospital emergency departments (3 children were admitted), and 1 patient was managed in a physician's office. Symptoms reported were tachycardia, drowsiness, nausea, hypertension, and vomiting. A seizure was reported in one child who had recently started atomoxetine therapy. No arrhythmias beyond sinus tachycardia were reported. Mean maximum heart rate in patients with tachycardia was 131 ± 14 beats/min. The mean dose ingested, categorized by medical outcome, was: no effect (n = 22), 40 ± 32 mg; minor effect (n = 14), 167 ± 221 mg; and moderate effect (n = 4), 249 ± 326 mg. There were no major outcomes or fatalities. The lowest dose ingested that resulted in hypertension was 480 mg, in a 14-year-old girl (BP 136/95 mm Hg).

CONCLUSIONS:

In this case series, clinically significant cardiovascular effects requiring direct intervention did not occur. Activated charcoal and/or observation appear to be sufficient for accidental ingestion. Further investigation may be needed to indicate whether seizures occur from atomoxetine ingestion.
Functional Dissociation of the Basolateral Transcytotic Compartment from the Apical Phago-lysosomal Compartment in Human Osteoclasts
Authors: Meagher James , Zellweger René , Filgueira Luis
Published: May 2005

Tartrate-resistant acid phosphatase (TRAP) is essential for elimination of Staphylococcus aureus, the main infectious agent responsible for osteomyelitis. This in vitro study investigated uptake and processing of fluorescence-labeled S. aureus by human osteoclasts and dendritic cells. The cells were stained for TRAP and the acidic compartment using a fluorescence-based protocol. In dendritic cells, TRAP and bacteria were colocalized. In osteoclasts, there was no colocalization of bacteria, TRAP, or the acidic compartment, indicating that there are three distinct vesicular compartments: the apical phago-lysosomal compartment, the basal secretory compartment, and the basolateral transcytotic compartment. Dissociation of the TRAP-containing transcytotic vesicles from the apical phago-lysosomal compartment may restrain osteoclasts from eliminating S. aureus.
5-Hydroxytryptamine (5HT) Receptors in the Heart Valves of Cynomolgus Monkeys and Sprague-Dawley Rats
Authors: Elangbam Chandikumar S. , Lightfoot Ruth M. , Yoon Lawrence W. , Creech Donald R. , Geske Robert S. , Crumbley Christopher W. , Gates Lisa D. , Wall Henry G.
Published: May 2005

5-Hydroxytryptamine-2B receptor (5HT2BR) stimulation is known to cause fibroblast mitogenesis, and the mitogenic effect has been proposed to trigger valvular heart disease in humans. In this study, we used real-time polymerase chain reaction (TaqMan) to quantify transcript levels of 5HT2B, 5HT2C, and 5HT1B receptors and immunohistochemistry (IHC) to detect the tissue localization of these receptors in the normal heart valves of cynomolgus (CM) monkeys and Sprague-Dawley (S-D) rats. In both species, positive immunostaining was noted for 5HT1B and 5HT2B receptors in mitral, tricuspid, aortic, and pulmonary valves, and the cell types showing positive staining were interstitial cells and endothelial cells lining the valve leaflet. In CM monkeys, 5HT2CR was expressed only in the endothelial cells lining the leaflet, whereas S-D valves were negative for this receptor. IHC results were correlated with 5HT2B and 5HT1B receptor transcripts for all four valves. However, 5HT2C receptor transcripts were lower than 5HT2B or 5HT1B in all CM monkey valves, whereas 5HT2C transcripts were below the level of detection in any of the S-D rat valves. Our data showed the expression of 5HT2B, 5HT1B, and 5HT2C receptors in the normal heart valves of CM monkeys and S-D rats, and IHC and TaqMan techniques may be used to study the potential mechanism of compounds with 5HT2BR agonist activity.
Tissue-specific Tropomyosin Isoform Composition
Authors: Schevzov Galina , Vrhovski Bernadette , Bryce Nicole S. , Elmir Sarah , Qiu Min Ru , O'Neill Geraldine M. , Yang Nan , Verrills Nicole M. , Kavallaris Maria , Gunning Peter W.
Published: May 2005

Four distinct genes encode tropomyosin (Tm) proteins, integral components of the actin microfilament system. In non-muscle cells, over 40 Tm isoforms are derived using alternative splicing. Distinct populations of actin filaments characterized by the composition of these Tm isoforms are found differentially sorted within cells ( Gunning et al. 1998b ). We hypothesized that these distinct intracellular compartments defined by the association of Tm isoforms may allow for independent regulation of microfilament function. Consequently, to understand the molecular mechanisms that give rise to these different microfilaments and their regulation, a cohort of fully characterized isoform-specific Tm antibodies was required. The characterization protocol initially involved testing the specificity of the antibodies on bacterially produced Tm proteins. We then confirmed that these Tm antibodies can be used to probe the expression and subcellular localization of different Tm isoforms by Western blot analysis, immunofluorescence staining of cells in culture, and immunohistochemistry of paraffin wax-embedded mouse tissues. These Tm antibodies, therefore, have the capacity to monitor specific actin filament populations in a range of experimental systems.
Chondrogenic Potential of Mouse Calvarial Mesenchyme
Authors: Åberg Thomas , Rice Ritva , Rice David , Thesleff Irma , Waltimo-Sirén Janna
Published: May 2005

Facial and calvarial bones form intramembranously without a cartilagenous model; however, cultured chick calvarial mesenchyme cells may differentiate into both osteoblasts and chondroblasts and, in rodents, small cartilages occasionally form at the sutures in vivo. Therefore, we wanted to investigate what factors regulate normal differentiation of calvarial mesenchymal cells directly into osteoblasts. In embryonic mouse heads and in cultured tissue explants, we analyzed the expression of selected transcription factors and extracellular matrix molecules associated with bone and cartilage development. Cartilage markers Sox9 and type II collagen were expressed in all craniofacial cartilages. In addition, Msx2 and type I collagen were expressed in sense capsule cartilages. We also observed that the undifferentiated calvarial mesenchyme and the osteogenic fronts in the jaw expressed Co∗∗∗l2A1. Moreover, we found that cultured mouse calvarial mesenchyme could develop into cartilage. Of the 49 explants that contained mesenchyme, intramembranous ossification occurred in 35%. Only cartilage formed in 4%, and both cartilage and bone formed in 4%. Our study confirms that calvarial mesenchyme, which normally gives rise to intramembranous bone, also has chondrogenic potential.
Ex Vivo Modeling of Oral HIV Transmission in Human Palatine Tonsil
Authors: Maher Diane M. , Zhang Zhi-Qiang , Schacker Timothy W. , Southern Peter J.
Published: May 2005

The majority of newly acquired HIV infections are believed to occur following transmission of virus infectivity across mucosal surfaces, although many mechanistic details still remain unresolved. We have used human ex vivo organ cultures and primary cell populations to analyze the cellular and molecular basis for mucosal HIV transmission. By using human palatine tonsil from routine tonsillectomies and semen from HIV-positive donors, we have created an experimental equivalent to oral HIV transmission. HIV infection was readily transferred into tonsillar lymphocytes, but this transmission into lymphocytes was dramatically reduced when the exposed lymphocyte populations were protected by intact mucosal surfaces. In this study, we consider the impact that leukocyte activation and morphological aberrations in surface structure may have on susceptibility to primary HIV infection and introduce novel time-lapse confocal microscopy procedures that begin to reveal the dynamic complexity associated with cell-mediated HIV transmission. This manuscript contains online supplemental material at http://www.jhc.org . Please visit this article online to view these materials.
Attenuation of Accumulation of Neointimal Lipid by Pioglitazone in Mice Genetically Deficient in Insulin Receptor Substrate-2 and Apolipoprotein E
Authors: Clough Maria H. , Schneider David J. , Sobel Burton E. , White Morris F. , Wadsworth Marilyn P. , Taatjes Douglas J.
Published: May 2005

Rupture of vulnerable atherosclerotic plaques that are characterized by extensive neointimal accumulation of lipid is a cause of acute coronary syndromes. To identify whether insulin resistance alters atherogenesis, we characterized the composition of atherosclerotic lesions in the proximal aortas in mice deficient in apolipoprotein E (ApoE−/-) and in ApoE−/- mice in which insulin resistance was intensified by a concomitant heterozygous deficiency in insulin receptor substrate type 2 (IRS2+/- ApoE−/- mice). In addition, we characterized the effect of an insulin sensitizer, pioglitazone, on the atherogenesis in IRS2+/- ApoE−/- mice. The extent of the aortic intima occupied by lesion was increased in the IRS2+/- ApoE−/- compared with ApoE−/- mice (79 ± 3% compared with 68 ± 8%, p<0.05). Treatment with pioglitazone decreased the neointimal content of lipid in 20-week-old mice from 50 ± 6% to 30 ± 7%, p=0.005 and decreased the cellularity reflected by the multisection cross-sectional areas of lesions comprising cells in atheroma from 24 ± 1% to 19 ± 3%, p=0.018. Accordingly, genetically induced intensification of insulin resistance increases atheroma formation. Furthermore, attenuation of insulin resistance by treatment with pioglitazone decreases accumulation of lipid in the neointima.
Multisensory Space Representations in the Macaque Ventral Intraparietal Area
Authors: Schlack Anja , Sterbing-D'Angelo Susanne J. , Hartung Klaus , Hoffmann Klaus-Peter , Bremmer Frank
Published: May 2005

Animals can use different sensory signals to localize objects in the environment. Depending on the situation, the brain either integrates information from multiple sensory sources or it chooses the modality conveying the most reliable information to direct behavior. This suggests that somehow, the brain has access to a modality-invariant representation of external space. Accordingly, neural structures encoding signals from more than one sensory modality are best suited for spatial information processing. In primates, the posterior parietal cortex (PPC) is a key structure for spatial representations. One substructure within human and macaque PPC is the ventral intraparietal area (VIP), known to represent visual, vestibular, and tactile signals. In the present study, we show for the first time that macaque area VIP neurons also respond to auditory stimulation. Interestingly, the strength of the responses to the acoustic stimuli greatly depended on the spatial location of the stimuli [i.e., most of the auditory responsive neurons had surprisingly small spatially restricted auditory receptive fields (RFs)].

Given this finding, we compared the auditory RF locations with the respective visual RF locations of individual area VIP neurons. In the vast majority of neurons, the auditory and visual RFs largely overlapped. Additionally, neurons with well aligned visual and auditory receptive fields tended to encode multisensory space in a common reference frame. This suggests that area VIP constitutes a part of a neuronal circuit involved in the computation of a modality-invariant representation of external space.
Cocaine-Induced Reinstatement Requires Endogenous Stimulation of μ-Opioid Receptors in the Ventral Pallidum
Authors: Tang Xing-Chun , McFarland Krista , Cagle Stephanie , Kalivas Peter W.
Published: May 2005

The projection from the nucleus accumbens to the ventral pallidum regulates the reinstatement of cocaine seeking in rats extinguished from cocaine self-administration. This projection coexpresses GABA and enkephalin, posing a role for μ-opioid receptors in the ventral pallidum in mediating the reinstatement of cocaine seeking. Rats were extinguished from cocaine self-administration, and the reinstatement of active lever pressing by cocaine was blocked by intra-ventral pallidum administration of the μ receptor antagonist Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2(CTAP) (0.03-3.0 μg). Conversely, stimulating μ receptors with morphine (1-30 μg) in the ventral pallidum reinstated cocaine seeking. The ability of intra-ventral pallidum morphine to reinstate lever pressing was blocked by co-microinjection of the μ antagonist CTAP and was augmented by systemic cocaine administration. The reinstatement of cocaine seeking was associated with reduced extracellular GABA in the ventral pallidum, and the reduction in GABA was also prevented by blocking μ receptors with CTAP (10 μm). Although immunoblotting revealed that neither the total tissue concentration nor the membrane insertion of μ receptors in the ventral pallidum was altered by withdrawal from cocaine, the capacity of morphine (0.01-10 μm) to reduce ventral pallidum levels of extracellular GABA was augmented in rats extinguished from cocaine self-administration. These data are consistent with the reinstatement of cocaine seeking being modulated in part by coreleased enkephalin and GABA from the accumbens-ventral pallidal projection, a modulation that may involve the inhibition of GABA release by presynaptic μ receptors.
The Anti-Apoptotic, Glucocorticoid Receptor Cochaperone Protein BAG-1 Is a Long-Term Target for the Actions of Mood Stabilizers
Authors: Zhou Rulun , Gray Neil A. , Yuan Peixiong , Li Xiaoxia , Chen Jingshan , Chen Guang , Damschroder-Williams Patricia , Du Jing , Zhang Lei , Manji Husseini K.
Published: May 2005

Increasing data suggest that impairments of cellular plasticity/resilience underlie the pathophysiology of bipolar disorder. A series of microarray studies with validating criteria have recently revealed a common, novel target for the long-term actions of the structurally highly dissimilar mood stabilizers lithium and valproate: BAG-1 [BCL-2 (B-cell CLL/lymphoma 2)-associated athanogene]. Because BAG-1 attenuates glucocorticoid receptor (GR) nuclear translocation, activates ERK (extracellular signal-regulated kinase) MAP (mitogen-activated protein) kinases, and potentiates anti-apoptotic functions of BCL-2, extensive additional studies were undertaken. Chronic administration of both agents at therapeutic doses increased the expression of BAG-1 in rat hippocampus. Furthermore, these findings were validated at the protein level, and the effects were seen in a time frame consistent with therapeutic effects and were specific for mood stabilizers. Functional studies showed that either lithium or valproate, at therapeutically relevant levels, inhibited dexamethasone-induced GR nuclear translocation and inhibited GR transcriptional activity. Furthermore, small interfering RNA studies showed that these inhibitory effects on GR activity were mediated, at least in part, through BAG-1. The observation that BAG-1 inhibits glucocorticoid activation suggests that mood stabilizers may counteract the deleterious effects of hypercortisolemia seen in bipolar disorder by upregulating BAG-1. Additionally, these studies suggest that regulation of GR-mediated plasticity may play a role in the treatment of bipolar disorder and raise the possibility that agents affecting BAG-1 more directly may represent novel therapies for this devastating illness.
Locus Ceruleus Control of Slow-Wave Homeostasis
Authors: Cirelli Chiara , Huber Reto , Gopalakrishnan Anupama , Southard Teresa L. , Tononi Giulio
Published: May 2005

Sleep intensity is regulated by the duration of previous wakefulness, suggesting that waking results in the progressive accumulation of sleep need (Borbély and Achermann, 2000). In mammals, sleep intensity is reflected by slow-wave activity (SWA) in the nonrapid eye movement (NREM) sleep electroencephalogram, which increases in proportion to the time spent awake. However, the mechanisms responsible for the increase of NREM SWA after wakefulness remain unclear. According to a recent hypothesis (Tononi and Cirelli, 2003), the increase in SWA occurs because during wakefulness, many cortical circuits undergo synaptic potentiation, as evidenced by the widespread induction of long-term potentiation (LTP)-related genes in the brain of awake animals. A direct prediction of this hypothesis is that manipulations interfering with the induction of LTP-related genes should result in a blunted SWA response.

Here, we examined SWA response in rats in which cortical norepinephrine (NA) was depleted, a manipulation that greatly reduces the induction of LTP-related genes during wakefulness (Cirelli and Tononi, 2004). We found that the homeostatic response of the lower-range SWA was markedly and specifically reduced after NA depletion. These data suggest that the wake-dependent accumulation of sleep need is causally related to cellular changes dependent on NA release, such as the induction of LTP-related genes, and support the hypothesis that sleep SWA homeostasis may be related to synaptic potentiation during wakefulness.
A Cognitive-Relational Approach to Emotions—The Appraisal and Coping Components of Sadness, Shame, Guilt, Jealousy, and Disgust
Authors: Mikulincer Mario , Florian Victor
Published: May 2005

This study employs a cognitive-relational framework to examine the appraisal and coping components of five major negative emotions. Three hundred and fifty undergraduate students were asked to recall a personal experience involving one of five negative emotions (shame, guilt, sadness, jealousy, disgust) and to complete scales tapping the ways they appraise the emotion-arousing situations, the ways they describe their emotional inner state, and the ways they cope with this state. Results indicate that the five assessed emotions were clearly differentiated on the basis of cognitions about the external situation and the individual's inner state as well as on the basis of the reported coping strategies. The pattern of appraisal and coping of each emotion seems to support some of Lazarus' theoretical hypotheses.
Incorporating Learning Research into Instructional Program Design
Authors: Yordy Laura
Published: May 2005

An interactive videodisc program on primates was developed to help upper elementary school students learn problem-solving skills as well as information about primates. The program is student-driven, encouraging the student to think like a scientist as he/she carries out a set of “missions” to study primates: making hypotheses, collecting observations, drawing conclusions, and solving problems. Each aspect of the program is based upon recent research in cognitive strategies and learning theory, as well as standard instructional design principles. Research indicates the advantages of presenting a theme and background information, structuring the material according to that schema, providing help when requested, and making feedback constructive. Teaching problem solving is, essentially, teaching students to think for themselves. This requires allowing students to work in teams to analyze the problem, conduct their own inquiry, and experience the satisfaction of a solution. Interactive videodisc offers several advantages for this type of project.
Dreams of the Dying Patient: An Exploration of Content
Authors: Prince Pamela N. , Hoffmann Robert F.
Published: May 2005

This study examined the dreams of eight individuals admitted to the Palliative Care Unit of the Elisabeth Bruyere Health Centre, Ottawa, Canada. Content analysis of the dream reports in this sample supports the hypothesis that a continuity exists between dreaming and waking experience [1]. Results do not indicate that themes of death and aggression, negative emotion, or infant and child characters are more prevalent among the dying. Discrepancies between the findings of this and previous studies are reinterpreted with regard to individual difference variables, such as phase of illness, age, premorbid interests, and medication. It is suggested that these variables, among others, comprise essential components of waking reality and should be considered in explorations of the dream content of dying individuals.
Redesigning Public Education via Technology
Authors: Robinson Isaiah E.
Published: May 2005

In recognition of the changing needs of students today and the ever increasing costs of education today, there is a need for an innovative plan which not only changes our educational structure but makes maximum use of computerized and automated education in striving toward new goals.
Corticosteroid Abuse Revisited
Authors: Goldberg Richard L. , Wise Thomas N.
Published: May 2005

Corticosteroids are potent but hazardous medications which can be abused. This article reviews existing literature on corticosteroid abuse and provides three new case reports. A profile of the corticosteroid patient is described and some treatment guidelines are offered. Hopefully, this article will sensitize physicians to the abuse potential of this class of drugs.
Reactions to Death in Residential Homes for the Aged
Authors: Matse Jan
Published: May 2005

Results are reported of a preliminary research among non-nursing staff, working in residential homes for the aged in the Netherlands, concerning the reactions of residents and of staff towards death. Feelings about the death of an individual resident, and about the continuous confrontation with death, and the ways these feelings become expressed in behaviour are discussed. The results suggest that the feelings are related to interaction patterns, and that the attitude of the staff develops over time.
Attitudes and Practice of Kuwaiti Women toward Breastfeeding
Authors: Al-Bustan Mahmoud H. Baqi
Published: May 2005

A survey was conducted to assess the attitudes towards breastfeeding, its prevalence and duration among Kuwaiti married women. Five hundred eighty-five women from different regions of the country with at least one child of their own, willing to furnish data were included in the survey. The results of this study show that 71 percent of newborns are breastfed at birth. The percentage of breast-fed infants declines to 50 percent by the time they are one month old, and to 10 percent among five-month-old infants. The expected duration of breastfeeding is about two months. This study also reveals a wide gap existing between the attitudes, knowledge and practice of breastfeeding among Kuwaiti women. Their attitude towards breastfeeding is largely positive. This study emphasizes that with appropriate health education and supportive measures sensitive to the needs of this community, breastfeeding can retain its integral part in the process of human reproduction and child development.
Distance Education: Applications in a Masters and Doctoral Program
Authors: Hesser Lois Ann , Kontos George
Published: May 2005

This article examines two graduate programs, one masters and one doctoral, that rely heavily on technological delivery systems. These systems include the use of audiobridge, videotapes, electronic mail, and compressed video. In addition, the programs utilize electronic library access, bulletin boards, and a special tool that was developed in-house, the Electronic Classroom. Included is a survey of “National Cluster” students in the doctoral program. The survey was used to assess the influence that technology, especially telecommunications, has had on the students' ability to complete their course of study, their career, and/or work status, and their personal interaction with friends and colleagues. Preliminary analysis of the survey data indicate that the instruction that these students received enabled them to perform in a positive way throughout their study. Student skill levels were increased, and the carryover to their work place was evident.
Profile of an Effective Hospice Team Member
Authors: Basile Joseph L. , Stone Donald B.
Published: May 2005

This study was designed to determine the competencies that hospice practitioners and experts in the field would agree upon as necessary attributes to being an effective hospice team member. The Delphi method was employed to solicit the desired competencies. Subsequently, after further data analysis, the final version of the questionnaire was reduced to twenty-nine items. The results indicated strong positive agreement between the rankings of the practitioners, emotional and interpersonal characteristics needed by hospice personnel to effectively function with the dying and their families in a hospital environment.
Anatomy of a Style Analyzer
Authors: Stratton Charles R.
Published: May 2005

Computer programs for analyzing writing style have grown in number and sophistication over the past decade, and the coming decade will see more and more of them. In order to know the capabilities and limitations of such programs and to decide if any of them are right for you, it is important to understand how they work. In this article, the author draws on his background in computational linguistics to explain how computerized style analyzers accomplish the things that they do.
Family Planning Decision-Making in a Polygynous Nepalese Family
Authors: Miller Robert A. , Fisher Andrew A.
Published: May 2005

This chronological study describes decision making about contraceptive usage by a polygynous family in Nepal. Open-ended interviews with the husband, separate structured interviews with each of three wives, discussions with officials at a laparoscopic sterilization camp, reports from family planning fieldworkers, the author's field notes, and a follow-up report a year later are the basis of the case description. The social reasons for polygyny, the role of the husband and wives in decision making, and the value of children are discussed in terms of the national family planning programs.
Imagery and Fantasy in Vietnam Veteran Psychiatric Inpatients
Authors: Starker Steven , Jolin Annette
Published: May 2005

Aspects of volitional and spontaneous imagery/fantasy are examined in hospitalized psychiatric patients with and without combat experience in Vietnam. The ability to create deliberate auditory imagery was unaffected by the combat experience; spontaneous imagery/fantasy in waking and sleeping were profoundly affected. Combat veterans were characterized by greater visual imagery and guilt in their daydreams, greater impairment in attention/concentration, and greater sleep disturbance than noncombat veterans. Results support the clinical conceptualization of post-traumatic stress syndrome as well as the notion of individual fantasy styles.
An Educational Intervention Using the Agency for Health Care Policy and Research Depression Guidelines among Internal Medicine Residents
Authors: Kick Steven D.
Published: May 2005

Objective:

To determine if a brief educational intervention utilizing the Agency for Health Care Policy and Research (AHCPR) Depression Guidelines would effect improved recognition of depressed patients, as well as improved attitudes and knowledge, among Internal Medicine housestaff.

Method:

This was a randomized trial of an educational intervention for Internal Medicine residents. All patients attending the resident clinics were screened using the Center for Epidemiologic Studies Depression Scale. Persons scoring greater than 16 constituted the prospective cohort. Three hundred eighty-four patients were screened for entry into the study. Of 160 persons meeting the entry criteria, follow up was available on seventy-two (60%). Residents were randomly assigned to receive the educational intervention which consisted of three sessions where the residents received copies and instructions about the AHCPR depression guidelines and the use of a case-finding instrument for depression.

Results:

Non-recognized patients had milder symptoms of depression than did recognized patients. The presence of depressive symptoms was strongly related to measures of health status. Only seven of the seventy-two patients were identified as depressed and this was distributed equally between the two groups of residents. Intervention residents showed sustained improvement regarding depression criteria and the use of screening instruments at six months.

Conclusions:

A brief educational intervention effected changes in resident attitudes and knowledge regarding the care of depressed patients. Residents recognized patients with greater depressive symptoms than those with milder symptoms.
Aspects of Fear of Personal Death, Levels of Awareness, and Professional Affiliation among Dialysis Unit Staff Members
Authors: Ungar Lea , Florian Victor , Zernitsky-Shurka Esther
Published: May 2005

The purpose of the present study was to examine the expressions of fear of personal death among physicians, nurses, and social workers working in dialysis units at several general hospitals. Seventy-one dialysis unit staff members and sixty-eight staff members of optomology and oto-rhino laryngology wards, who served as a control group, responded on an individual basis to: 1) Fear of Personal Death Scale [1]; 2) Four TAT cards. Results indicated no differences in fear of personal death between the two main research groups both on the conscious and on below the conscious level. When compared to social workers, physicians received lower scores of fear of personal death on both levels, and nurses scores fell between the two professions. Clear gender differences were revealed. These results and their practical implications are discussed.
The Design of a Keyboarding Drill and Practice Program
Authors: Leigh William , Laycock Perry
Published: May 2005

Keyboarding skills are a necessary subject of instruction at all educational levels. This article describes a computer program which administers keyboarding practice lessons and speed drills. Also, the program provides facilities to support teacher-personalized lessons.
Mania in AIDS: Clinical Significance and Theoretical Considerations
Authors: El-Mallakh Rif S.
Published: May 2005

Cases of mania associated with acquired immune deficiency syndrome (AIDS) are reviewed in an attempt to elucidate patterns that may be helpful in guiding treatment, determining prognosis, and understanding pathophysiology. Fourteen well-described cases in the English language literature were critically reviewed. Data was collected regarding chronological appearance of signs and symptoms, specific psychiatric symptoms, associated neurologic and cognitive function, objective testing of brain structure and function, and outcome. When mania or hypomania occur in the setting of a human immunodeficiency virus (HIV) infection, it frequently occurs once and does not recur. AIDS-associated manic states are adequately responsive to available anti-manic agents, however, AIDS patients may be more prone to deleterious side effects. Although mania or hypomania may be the presenting complaints that lead to the discovery of human immunodeficiency virus (HIV) seropositive status, mania tends to occur in people exhibiting signs of immunodeficiency as is exemplified, in the sample, by death occurring within six months of the psychiatric presentation in nearly a quarter of the patients. It is hypothesized that AIDS-related mania and agitated psychosis may be related to increased intracellular free calcium.
Think Now—Write Later: The Triumphs and Traumas of a New Teacher of Technical Writing
Authors: Walter Marie-Louise
Published: May 2005

Teachers are recruited from the technical professions and from advanced composition courses to instruct the new discipline: technical writing. Students in a single class major and work in diverse fields. As a common denominator, organization, research, and writing a major paper are emphasized. Classroom discussion, specialized workshops, and individual conferences are utilized. Quality is the key.
Older Adults' Attitudes Toward Death: Links to Perceptions of Health and Concerns about End-of-Life Issues
Authors: Lockhart Lisa Klepac , Bookwala Jamila , Fagerlin Angela , Coppola Kristen M. , Ditto Peter H. , Danks Joseph H. , Smucker William D.
Published: May 2005

The current study had two primary goals, to determine whether: 1) self-rated mental and physical health, pain, and experience with health problems were predictors of elderly adults' attitudes toward death; and 2) death attitudes predict end-of-life medical treatment concerns. Participants were 109 adults, 65 years of age and older ( M=78.74 years), recruited from the local community. Regression analyses indicated that poorer perceived physical health predicted a greater likelihood of viewing death as an escape, and poorer perceived mental health predicted a greater fear of death. Viewing death as an escape and fearing death predicted end-of-life medical treatment concerns; a greater endorsement of either attitude predicted more concern. Possible explanations for the links between perceived health, attitudes toward death, and concern about end-of-life issues are suggested.