bluuebunny/crossref_metadata_2025 huggingface dataset:
Caenorhabditis elegans MPP+ Model of Parkinson’s Disease for High-Throughput Drug Screenings
Authors: Braungart Evelyn , Gerlach Manfred , Riederer Peter , Baumeister Ralf , Hoener Marius C.
Published: November 2004

The neurotoxin MPTP and its active metabolite MPP+ cause Parkinson’s disease (PD)-like symptoms in vertebrates by selectively destroying dopaminergic neurons in the substantia nigra. MPTP/MPP+ models have been established in rodents to screen for pharmacologically active compounds. In addition to being costly and time consuming, these animal models are not suitable for large scale testings using compound libraries. We present a novel MPP+-based model for high-throughput screenings using the nematode Caenorhabditis elegans. Incubation of C. elegans with MPTP or its active metabolite MPP+ resulted in strong symptomatic defects including reduced mobility and increased lethality, and is correlated with a specific degeneration of the dopaminergic neurons. The phenotypic consequences of MPTP/MPP+ treatments were recorded using automated hardware and software for quantification. Incubation of C. elegans with a variety of pharmacologically active components used in PD treatment reduced the MPP+-induced defects. Our data suggest that the C. elegans MPTP/MPP+ model can be used for the quantitative evaluation of anti-PD drugs.
Increased expression of the Abcg2 transporter during erythroid maturation plays a role in decreasing cellular protoporphyrin IX levels
Authors: Zhou Sheng , Zong Yang , Ney Paul A. , Nair Geeta , Stewart Clinton F. , Sorrentino Brian P.
Published: November 2004

ABCG2/BCRP is a member of the adenosine triphosphate–binding cassette (ABC) transporter family and is expressed in intestine, kidney, and liver, where it modulates the absorption and excretion of xenobiotic compounds. ABCG2 is also expressed in hematopoietic stem cells and erythroid cells; however, little is known regarding its role in hematopoiesis. Abcg2 null mice have increased levels of protoporphyrin IX (PPIX) in erythroid cells, yet the mechanism for this remains uncertain. We have found that Abcg2 mRNA expression was up-regulated in differentiating erythroid cells, coinciding with increased expression of other erythroid-specific genes. This expression pattern was associated with significant amounts of ABCG2 protein on the membrane of mature peripheral blood erythrocytes. Erythroid cells engineered to express ABCG2 had significantly lower intracellular levels of PPIX, suggesting the modulation of PPIX level by ABCG2. This modulating activity was abrogated by treatment with a specific ABCG2 inhibitor, Ko143, implying that PPIX may be a direct substrate for the transporter. Taken together, our results demonstrate that ABCG2 plays a role in regulating PPIX levels during erythroid differentiation and suggest a potential role for ABCG2 as a genetic determinant in erythropoietic protoporphyria.
Aspergillus fumigatus suppresses the human cellular immune response via gliotoxin-mediated apoptosis of monocytes
Authors: Stanzani Marta , Orciuolo Enrico , Lewis Russell , Kontoyiannis Dimitrios P. , Martins Sergio L. R. , St. John Lisa S. , Komanduri Krishna V.
Published: November 2004

Aspergillus fumigatus (AF) is a ubiquitous mold and is the most common cause of invasive aspergillosis, an important source of morbidity and mortality in immunocompromised hosts. Using cytokine flow cytometry, we assessed the magnitude of functional CD4+ and CD8+ T-cell responses following stimulation with Aspergillus antigens. Relative to those seen with cytomegalovirus (CMV) or superantigen stimulation, responses to Aspergillus antigens were near background levels. Subsequently, we confirmed that gliotoxin, the most abundant mycotoxin produced by AF, was able to suppress functional T-cell responses following CMV or staphylococcal enterotoxin B (SEB) stimulation. Additional studies demonstrated that crude AF filtrates and purified gliotoxin inhibited antigen-presenting cell function and induced the preferential death of monocytes, leading to a marked decrease in the monocyte-lymphocyte ratio. Analysis of caspase-3 activation confirmed that gliotoxin preferentially induced apoptosis of monocytes; similar effects were observed in CD83+ monocyte-derived dendritic cells. Importantly, the physiologic effects of gliotoxin in vitro were observed below concentrations recently observed in the serum of patients with invasive aspergillosis. These studies suggest that the production of gliotoxin by AF may constitute an important immunoevasive mechanism that is mediated by direct effects on antigen-presenting cells and both direct and indirect effects on T cells.
The critical role of arginine residues in the binding of human monoclonal antibodies to cardiolipin
Authors: Giles Ian , Lambrianides Nancy , Latchman David , Chen Pojen , Chukwuocha Reginald , Isenberg David , Rahman Anisur
Published: November 2004

Previously we reported that the variable heavy chain region (VH) of a human beta2 glycoprotein I-dependent monoclonal antiphospholipid antibody (IS4) was dominant in conferring the ability to bind cardiolipin (CL). In contrast, the identity of the paired variable light chain region (VL) determined the strength of CL binding. In the present study, we examine the importance of specific arginine residues in IS4VH and paired VL in CL binding. The distribution of arginine residues in complementarity determining regions (CDRs) of VH and VL sequences was altered by site-directed mutagenesis or by CDR exchange. Ten different 2a2 germline gene-derived VL sequences were expressed with IS4VH and the VH of an anti-dsDNA antibody, B3. Six variants of IS4VH, containing different patterns of arginine residues in CDR3, were paired with B3VL and IS4VL. The ability of the 32 expressed heavy chain/light chain combinations to bind CL was determined by ELISA. Of four arginine residues in IS4VH CDR3 substituted to serines, two residues at positions 100 and 100 g had a major influence on the strength of CL binding while the two residues at positions 96 and 97 had no effect. In CDR exchange studies, VL containing B3VL CDR1 were associated with elevated CL binding, which was reduced significantly by substitution of a CDR1 arginine residue at position 27a with serine. In contrast, arginine residues in VL CDR2 or VL CDR3 did not enhance CL binding, and in one case may have contributed to inhibition of this binding. Subsets of arginine residues at specific locations in the CDRs of heavy chains and light chains of pathogenic antiphospholipid antibodies are important in determining their ability to bind CL.
The impact of physical therapy on functional outcomes after stroke: what's the evidence?
Authors: Van Peppen R PS , Kwakkel G , Wood-Dauphinee S , Hendriks H JM , Van der Wees Ph J , Dekker J
Published: November 2004

Objective: To determine the evidence for physical therapy interventions aimed at improving functional outcome after stroke.

Methods: MEDLINE, CINAHL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, DARE, PEDro, EMBASE and DocOnline were searched for controlled studies. Physical therapy was divided into 10 intervention categories, which were analysed separately. If statistical pooling (weighted summary effect sizes) was not possible due to lack of comparability between interventions, patient characteristics and measures of outcome, a bestresearch synthesis was performed. This best-research synthesis was based on methodological quality (PEDro score).

Results: In total, 151 studies were included in this systematic review; 123 were randomized controlled trials (RCTs) and 28 controlled clinical trials (CCTs). Methodological quality of all RCTs had a median of 5 points on the 10-point PEDro scale (range 2–8 points). Based on high-quality RCTs strong evidence was found in favour of task-oriented exercise training to restore balance and gait, and for strengthening the lower paretic limb. Summary effect sizes (SES) for functional outcomes ranged from 0.13 (95% CI 0.03–0.23) for effects of high intensity of exercise training to 0.92 (95% CI 0.54–1.29) for improving symmetry when moving from sitting to standing. Strong evidence was also found for therapies that were focused on functional training of the upper limb such as constraint-induced movement therapy (SES 0.46; 95% CI 0.07–0.91), treadmill training with or without body weight support, respectively 0.70 (95% CI 0.29–1.10) and 1.09 (95% CI 0.56–1.61), aerobics (SES 0.39; 95% CI 0.05–0.74), external auditory rhythms during gait (SES 0.91; 95% CI 0.40–1.42) and neuromuscular stimulation for glenohumeral subluxation (SES 1.41; 95% CI 0.76–2.06). No or insufficient evidence in terms of functional outcome was found for: traditional neurological treatment approaches; exercises for the upper limb; biofeedback; functional and neuromuscular electrical stimulation aimed at improving dexterity or gait performance; orthotics and assistive devices; and physical therapy interventions for reducing hemiplegic shoulder pain and hand oedema.

Conclusions: This review showed small to large effect sizes for task-oriented exercise training, in particular when applied intensively and early after stroke onset. In almost all high-quality RCTs, effects were mainly restricted to tasks directly trained in the exercise programme.
ARAP3 is transiently tyrosine phosphorylated in cells attaching to fibronectin and inhibits cell spreading in a RhoGAP-dependent manner
Authors: Stacey T. T. I , Nie Zhongzhen , Stewart Ashley , Najdovska Meri , Hall Nathan E. , He Hong , Randazzo Paul A. , Lock Peter
Published: November 2004

ARAP3 is a GTPase activating protein (GAP) for Rho and Arf GTPases that is implicated in phosphoinositide 3-kinase (PI 3-kinase) signalling pathways controlling lamellipodia formation and actin stress fibre assembly. We have identified ARAP3 as a phosphorylated target of protein tyrosine kinases. In cells, ARAP3 was tyrosine phosphorylated when co-expressed with Src-family kinases (SFKs), upon stimulation with growth factors and during adhesion to the extracellular matrix (ECM) substrate fibronectin. Adhesion-induced phosphorylation of ARAP3 was suppressed by selective inhibitors of Src-family kinases and PI 3-kinase and by a Src dominant interfering mutant. Inducible expression of ARAP3 in HEK293 epithelial cells resulted in increased cell rounding, membrane process formation and cell clustering on ECM substrates. In contrast, ARAP3 dramatically slowed the kinetics of cell spreading on fibronectin but had no effect on cell adhesion. These effects of ARAP3 required a functional Rho GAP domain and were associated with reduced cellular levels of active RhoA and Rac1 but did not require the sterile alpha motif (SAM) or Arf GAP domains. Mutation of two phosphorylation sites, Y1399 and Y1404, enhanced some ARAP3 activities, suggesting that ARAP3 may be negatively regulated by phosphorylation on these tyrosine residues. These results implicate ARAP3 in integrin-mediated tyrosine kinase signalling pathways controlling Rho GTPases and cell spreading.
Intranuclear membrane structure formations by CaaX-containing nuclear proteins
Authors: Ralle Thorsten , Grund Christine , Franke Werner W. , Stick Reimer
Published: November 2004

The nuclear lamina is a protein meshwork lining the nucleoplasmic face of the nuclear envelope. Association of lamins with the inner nuclear membrane is mediated by specific modifications in the CaaX motif at their C-termini. B-type lamins are permanently isoprenylated whereas lamin A loses its modification by a lamin A-specific processing step after incorporation into the lamina. Lamins are differentially expressed during development and tissue differentiation. Here we show that an increased synthesis of lamins B1 and B2 in amphibian oocytes induces the formation of intranuclear membrane structures that form extensive arrays of stacked cisternae. These `lamin membrane arrays' are attached to the inner nuclear membrane but are not continuous with it. Induction of this membrane proliferation depends on CaaX-specific posttranslational modification. Moreover, in transfected HeLa cells, chimeric GFP containing a nuclear localization signal and a C-terminal CaaX motif of N-Ras induces intranuclear membrane stacks that resemble those induced by lamins and ER-like cisternae that are induced in the cytoplasm upon increased synthesis of integral ER membrane proteins. Implications for the synthesis of CaaX-containing proteins are discussed and the difference from intranuclear fibrous lamina annulate lamellae formations is emphasized.
The lamin CxxM motif promotes nuclear membrane growth
Authors: Prüfert Kristina , Vogel Annette , Krohne Georg
Published: November 2004

We analyzed the influence of lamins on nuclear envelope growth in cultured Xenopus A6 cells by the overexpression of human lamin A, Xenopus and zebrafish lamins B2 and Drosophila lamins Dm0 and C as GFP fusion proteins. Lamins containing a CxxM motif in their primary sequence (lamins A, B2, Dm0) induced the formation of lobulated nuclei with multi-membrane-layered, highly folded nuclear membranes and intranuclear membrane assemblies, as observed by electron microscopy. Such morphological alterations were not observed with Drosophila lamin C, a lamin without this motif or with a lamin B2 mutant (B2-SxxM) where the cysteine of the CxxM motif is replaced by a serine. Drosophila lamin C mutants containing a CxxM motif behaved like B-type lamins thus confirming that this tetrapeptide is directly involved in the morphological changes we observed. Nuclear membrane proliferation could also be induced by lamin B2 in COS-7 cells and in zebrafish embryos but not by human lamin A in COS-7 cells. We speculate that the human lamin A is incompletely processed in Xenopus A6 cells and therefore behaves in this cell line like a B-type lamin. Our results indicate that the CxxM motif of B-type lamins has a dual function: it mediates lamin targeting to the inner nuclear membrane thereby promoting nuclear membrane growth.
Coadministration of Gatifloxacin and Multivitamin Preparation Containing Minerals: Potential Treatment Failure in an Elderly Patient
Authors: Mallet Louise , Huang Allen
Published: November 2004

OBJECTIVE:

To report a case of probable treatment failure in a patient receiving gatifloxacin and a multivitamin preparation containing minerals.

CASE SUMMARY:

A 77-year-old white woman was prescribed gatifloxacin for hospital-acquired bacterial pneumonia. She was also receiving calcium carbonate 500 mg twice daily and a multivitamin preparation containing minerals once a day. Three days after gatifloxacin was started, the patient was still febrile, coughing, and not responding clinically. It was noted that nurses were administering the gatifloxacin tablet at the same time as the multivitamin tablet. The time of administration for gatifloxacin was changed to 6 hours after the patient received her multivitamin preparation. Two days later, she clinically improved.

DISCUSSION:

Studies have shown that the bioavailability of gatifloxacin is decreased with concurrent administration of antacids containing aluminum or magnesium; dietary supplements containing zinc, magnesium, and iron; multivitamin preparations containing minerals; and sucralfate. An objective causality assessment revealed that the adverse drug effect was probable.

CONCLUSIONS:

This case illustrates the need to recognize this potential interaction and to know how to avoid possible treatment failure.
Neurotrophin Signaling through the p75 Receptor Is Deficient intraf6-/- Mice
Authors: Yeiser E. Carden , Rutkoski Nancy J. , Naito Asuka , Inoue Jun-ichiro , Carter Bruce D.
Published: November 2004

Activation of the neurotrophin receptor p75 has been shown to elicit opposing cellular signals. Depending on the context of the cell, p75 will either promote survival or induce apoptosis after neurotrophin stimulation. p75-induced apoptosis occurs through activation of c-Jun N-terminal kinase (JNK), whereas the survival signal is mediated by nuclear factor κB (NFκB). The receptor proximal signals that produce these responses are unknown, although several molecules have been identified that associate with the intracellular domain of p75. One such interactor, TRAF6, a member of the tumor necrosis factor receptor-associated factor family, has been implicated in p75 signaling. To assess the role of TRAF6 in p75 signaling, we analyzed mice with this gene deleted. In Schwann cells isolated fromtraf6+/+ animals, NGF elicited an 80% increase in transcription of an NFκB reporter; however, intraf6-/- cells, the NGF response was abrogated. Similarly, NGF activation of JNK was not apparent in Schwann cells from mice lackingtraf6. Deficiencies in p75 signaling intraf6-/- animals resulted in a loss of p75-mediated apoptosis. In sympathetic neurons cultured fromtraf6+/+ superior cervical ganglia (SCGs), there was an increase in JNK activation and apoptosis after BDNF binding to p75; however,traf6-/- neurons did not respond.In vivoduring naturally occurring cell death, there was a 55.6% reduction in TUNEL (terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling)-positive cells in the SCG of postnatal day 4traf6-/- animals relative totraf6+/+ littermates. These results indicate that TRAF6 plays an essential role in mediating p75 signal transduction and induction of apoptosis.
D2Dopamine Receptor-Mediated Modulation of Voltage-Dependent Na+Channels Reduces Autonomous Activity in Striatal Cholinergic Interneurons
Authors: Maurice Nicolas , Mercer Jeff , Chan C. Savio , Hernandez-Lopez Salvador , Held Joshua , Tkatch Tatiana , Surmeier D. James
Published: November 2004

Striatal cholinergic interneurons are critical elements of the striatal circuitry controlling motor planning, movement, and associative learning. Intrastriatal release of dopamine and inhibition of interneuron activity is thought to be a critical link between behaviorally relevant events, such as reward, and alterations in striatal function. However, the mechanisms mediating this modulation are unclear. Using a combination of electrophysiological, molecular, and computational approaches, the studies reported here show that D2dopamine receptor modulation of Na+currents underlying autonomous spiking contributes to a slowing of discharge rate, such as that seenin vivo. Four lines of evidence support this conclusion. First, D2receptor stimulation in tissue slices reduced the autonomous spiking in the presence of synaptic blockers. Second, in acutely isolated neurons, D2receptor activation led to a reduction in Na+currents underlying pacemaking. The modulation was mediated by a protein kinase C-dependent enhancement of channel entry into a slow-inactivated state at depolarized potentials. Third, the sodium channel blocker TTX mimicked the effects of D2receptor agonists on pacemaking. Fourth, simulation of cholinergic interneuron pacemaking revealed that a modest increase in the entry of Na+channels into the slow-inactivated state was sufficient to account for the slowing of pacemaker discharge. These studies establish a cellular mechanism linking dopamine and the reduction in striatal cholinergic interneuron activity seen in the initial stages of associative learning.
Memory-Like Alterations inAplysiaAxons after Nerve Injury or Localized Depolarization
Authors: Weragoda Ramal M. S. , Ferrer Elisa , Walters Edgar T.
Published: November 2004

Adaptive, long-term alterations of excitability have been reported in dendrites and presynaptic terminals but not along axons. Persistent enhancement of axonal excitability has been described in proximal nerve stumps at sites of nerve section in mammals, but this hyperexcitability is considered a pathological derangement important only as a cause of neuropathic pain. Identified neurons inAplysiawere used to test the hypothesis that either axonal injury or the focal depolarization that accompanies axonal injury can trigger a local decrease in action potential threshold [long-term hyperexcitability (LTH)] having memory-like properties. Nociceptive tail sensory neurons and a giant secretomotor neuron, R2, exhibited localized axonal LTH lasting 24 hr after a crush of the nerve or connective that severed the tested axons. Axons of tail sensory neurons and tail motor neurons, but not R2, displayed similar localized LTH after peripheral depolarization produced by 2 min exposure to elevated extracellular [K+]. Neither the induction nor expression of either form of LTH was blocked by saline containing 1% normal [Ca2+] during treatment or testing. However, both were prevented by local application of the protein synthesis inhibitors anisomycin or rapamycin. The features of (1) long-lasting alteration by localized depolarization, (2) restriction of alterations to intensely depolarized regions, and (3) dependence of the alterations on local, rapamycin-sensitive protein synthesis are shared with synaptic mechanisms considered important for memory formation. This commonality suggests that relatively simple, accessible axons may offer an opportunity to define fundamental plasticity mechanisms that were important in the evolution of memory.
The Role of Palmitoylation in Functional Expression of Nicotinic α7 Receptors
Authors: Drisdel Renaldo C. , Manzana Ehrine , Green William N.
Published: November 2004

Neuronal α-bungarotoxin receptors (BgtRs) are nicotinic receptors that require as yet unidentified post-translational modifications to achieve functional expression. In this study, we examined the role of protein palmitoylation in BgtR expression. BgtR α7 subunits are highly palmitoylated in neurons from brain and other cells capable of BgtR expression, such as pheochromocytoma 12 (PC12) cells. In PC12 cells, α7 subunits are palmitoylated with a stoichiometry of approximately one palmitate per subunit, and inhibition of palmitoylation blocks BgtR expression. In cells incapable of BgtR expression, such as human embryonic kidney cells, α7 subunits are not significantly palmitoylated. However, in these same cells, chimeric subunits with the N-terminal half of α7 fused to the C-terminal half of serotonin-3A receptor (α7/5-HT3A) subunits form functional BgtRs that are palmitoylated to an extent similar to that of BgtRα7 subunits in PC12 cells. Palmitoylation of PC12 and α7/5-HT3ABgtRs occurred during assembly in the endoplasmic reticulum (ER). In conclusion, our data indicate a function for protein palmitoylation in which palmitoylation of assembling α7 subunits in the ER has a role in the formation of functional BgtRs.
Postnatal Neurogenesis and Gliogenesis in the Olfactory Bulb from NG2-Expressing Progenitors of the Subventricular Zone
Authors: Aguirre Adan , Gallo Vittorio
Published: November 2004

We used a 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNP)-enhanced green fluorescent protein (EGFP) transgenic mouse to study postnatal subventricular zone (SVZ) progenitor fate, with a focus on the olfactory bulb (OB). The postnatal OB of the CNP-EGFP mouse contained EGFP+interneurons and oligodendrocytes. In the anterior SVZ, the majority of EGFP+progenitors were NG2+. These NG2+/EGFP+progenitors expressed the OB interneuron marker Er81, the neuroblast markers doublecortin (DC) and Distalless-related homeobox (DLX), or the oligodendrocyte progenitor marker Nkx2.2. In the rostral migratory stream (RMS), EGFP+cells displayed a migrating phenotype. A fraction of these cells were either NG2-/Er81+/DC+/DLX+or NG2+/Nkx2.2+. DiI (1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate) injection into the lateral ventricle (LV) of early postnatal mice demonstrated that NG2+/EGFP+progenitors migrate from the SVZ through the RMS into the OB. Moreover, fluorescence-activated cell-sorting-purified NG2+/CNP-EGFP+or NG2+/β-actin-enhanced yellow fluorescent protein-positive (EYFP+) progenitors transplanted into the early postnatal LV displayed extensive rostral and caudal migration. EYFP+or EGFP+graft-derived cells within the RMS were DLX+/Er81+or Nkx2.2+, migrated to the OB, and differentiated to interneurons and oligodendrocytes. In the subcortical white matter (SCWM), grafted cells differentiated to either oligodendrocytes or astrocytes. Transplantation of NG2+/EYFP+progenitors selectively purified from the SVZ showed that these cells were migratory and generated glia and neurons in the OB, hippocampus, and striatum. In contrast, cortical, OB, or cerebellar NG2+cells had a very limited migratory potential and gave rise to glia in the SCWM and striatum. Our findings indicate region-specific differences between NG2+progenitor cells and show that NG2+cells can migrate throughout the RMS and contribute to both gliogenesis and neurogenesis in the postnatal OB.
Evolutionary Perspectives on Emotion: Making Sense of What We Feel
Authors: Greenberg Leslie S.
Published: November 2004

Cognitive therapy typically has focused on cognitive regulators of affects, such as expectations, attributions, beliefs, and schemas (Beck, Rush, Shaw, & Emery, 1979). There has been far less focus on the role of affects in the process of the creation of meaning itself. However, the last ten years have witnessed an explosion of research on emotions, including their neuroarchitecture, their physiological regulators, their evolved functions, and the various unconscious algorithms that elicit them (Panksepp, 1998). There is increasing evidence, from different fields of research, for multiple and complex domains of cognition-emotion interaction, both slow and conscious, and fast and unconscious. This article explores some of these themes and indicates why an evolution-based approach to emotions, in hand with an understanding of developmental processes, can enrich our therapies and point to new ways of working directly with emotions.
Who Becomes a Depressive Ruminator? Developmental Antecedents of Ruminative Response Style
Authors: Spasojević Jelena , Alloy Lauren B.
Published: November 2004

Developmental antecedents of ruminative response style were examined in 137 college freshmen, who were followed prospectively for 2.5 years. Reports of mothers’ and fathers’ psychologically overcontrolling parenting as well as a history of childhood sexual (for women only) and emotional maltreatment were all related to ruminative response style. In addition, ruminative response style mediated the relationships between these developmental factors and the number of major depressive episodes experienced by participants during the follow-up period. Potential explanations and important implications of these findings are discussed.
Self-Directed Thought and Response to Treatment for Depression: A Preliminary Investigation
Authors: Ciesla Jeffrey A. , Roberts John E.
Published: November 2004

The study this article is based on investigated the role of self-directed attention in the maintenance of depressive episodes. Measures of rumination and self-consciousness were used to predict response to treatment for depression. Further, the study investigated the potential interplay between self-directed attention and negative cognition. Thirty-two participants completed measures of rumination, private self-consciousness, and negative cognition prior to receiving group psychoeducational treatment for depression. Analyses revealed that although the main effects of measures of self-directed attention and negative cognition were not statistically significant, the interaction between self-directed thought (particularly rumination) and negative cognitive style predicted change in severity of depressive symptoms over the course of the treatment program. These findings suggest that the degree to which heightened self-directed attention contributes to poor treatment outcome for depression varies as a function of cognitive style.
Delusions: A Cognitive Perspective
Authors: Beck Aaron T. , Rector Neil A.
Published: November 2004

The understanding of delusions, while historically focused on neuropsychological deficits, can be approached from the same cognitive perspective as that applied to other forms of psychopathology. The cross-sectional analysis of delusional thinking shows several cognitive characteristics: egocentric bias (irrelevant events are construed as self-relevant); externalizing bias (strong internal sensations or symptoms are attributed to external agents); and intentionalizing bias (other people’s behaviors are believed to be based on intentions—usually malevolent—towards the patient). In addition, defective reality testing precludes reevaluation and rejection of erroneous conclusions. Consequently, cognitive distortions such as selective abstraction, overgeneralization, and arbitrary inferences are prevalent. From a developmental perspective, grandiose delusions appear to arise from earlier daydreams of glory, serving as a compensation for feelings of loneliness, inadequacy, and inferiority. The daydreams become increasingly real to the patient until they become overt delusions. Persecutory delusions typically begin as a fear of retaliation or discrimination. Because of attentional bias, these fears receive pseudoconfirmation until they become fully formed beliefs that preempt normal information processing and displace more realistic beliefs.
A Cognitive Therapy Approach for Adult Attention Deficit/Hyperactivity Disorder
Authors: Ramsay Russell J. , Rostain Anthony L.
Published: November 2004

While attention deficit/hyperactivity disorder (ADHD) is the most prevalent behavioral disorder of childhood, the past decade has seen a rise in the number of adults presenting for treatment with difficulties related to ADHD. Few treatments (particularly psychosocial treatments) offered to adult patients with ADHD, however, have been empirically tested, much less been grounded in an overarching treatment model that captures the complexity of the various neurobiological, developmental, and psychological issues germane to this clinical population. The purpose of this article is to introduce a cognitive therapy approach for treating adults with ADHD. To do so we will describe the nature of ADHD, discuss some of the clinical issues unique to this diagnosis, and outline a cognitive therapy approach for conceptualizing and treating adult ADHD, integrating a number of case examples.
A Theoretical Approach to Measuring Quality of Life
Authors: Sousa Karen H. , Chen Fang Fang
Published: November 2004

The purpose of this article is to discuss conceptual issues surrounding health-related quality of life (HRQOL) and to provide an example of how structural equation modeling can address some of these conceptual issues. This article reports the development of the measurement model for overall quality of life, a dimension of HRQOL as conceptualized by Wilson and Cleary (1995). The sample (N = 1410) is from the AIDS Time-Oriented Health Outcome Study (ATHOS) databank, a longitudinal observational database of persons with HIV-associated illness. The hypothesized second-order factor model consists of 5 latent variables and 17 measured items. The fit indicators (RMSEA = .0717; SRMR = .0450; CFI = .951) suggest that the model provides an adequate description of the pattern of relationships in the data. A theoretical approach to HRQOL will expand its clinical use as an outcome measure and increase its relevance.
Instrument Translation and Evaluation of Equivalence and Psychometric Properties: The Chinese Sense of Coherence Scale
Authors: Tang Siew Tzuh , Dixon Jane
Published: November 2004

Translating well-established English instruments into target languages other than English and testing cross-cultural validity to prove that the same attributes are being measured in each cultural group or country are required before a multicultural or international study can be conducted and cross-cultural comparisons of study results can be applied. However, rigorous and systematic cross-cultural efforts to test the effectiveness of specific translation methods are rare. This article presents a model of translation processes and empirical validation of the translated instrument through description of the translation of a selected instrument—the Sense of Coherence (SOC) Scale—from English into Chinese. A cyclic process of forward translations, back translations, and expert evaluation of equivalence by bilingual and English speaking experts was conducted to achieve conceptual equivalence between the original and translated instruments. Empirical validation of the Chinese SOC scale data from a group of bilingual Chinese people demonstrated non-identical, but comparable, item and scale means and variances, internal consistency, and relationships to an external criterion. Advantages and difficulties of using multi-rounds, multi-experts, and multi-methods to establish translation equivalence and to validate the translated Chinese SOC scale are discussed.
Development of a Self-Efficacy Instrument for Coronary Artery Bypass Graft Patients
Authors: Barnason Susan , Zimmerman Lani , Atwood Jan , Nieveen Janet , Schmaderer Myra
Published: November 2004

Research related to self-efficacy has demonstrated that measures of this concept need to be specific to the behavior of interest. Self-efficacy is the degree of confidence one has to perform an activity. This article describes the development and testing of the Barnason Efficacy Expectation Scale (BEES). The instrument is a 15-item tool that uses a Likert scale to determine the coronary-artery-bypass-graft (CABG) patient’s self-efficacy related to the risk-reduction-related aspects of recovery and lifestyle adjustment following CABG surgery (physical functioning, psychosocial functioning, coronary artery disease risk factor modification and self-care management). Internal consistency reliability of the instrument was 0.93, and principal components analysis revealed a single factor (Eigenvalue = 10.59, percent variance = 70.61%). Three phases of tool development are described in the article that document satisfactory reliability and validity (face, content, criterion, and construct).
The Friedrich-Lively Instrument to Assess the Impact of Schizophrenia on Siblings (FLIISS)©: Part II—Reliability and Validity Assessment
Authors: Rubenstein Linda , Friedrich Rose Marie , Lively Sonja , Buckwalter Kathleen
Published: November 2004

Siblings of persons with schizophrenia who provide primary or secondary care for their sibling and support to parents may experience stress, decreased quality of life, grief, chronic illness, depression, and anxiety. The effects on siblings have not been widely studied and there have not been appropriate instruments to measure the types and degree of stress and associated mental, emotional, and physical distress. The Friedrich-Lively Instrument to Assess the Impact of Schizophrenia on Siblings (FLIISS) is a comprehensive instrument based on extensive research and work with siblings of persons with schizophrenia. Construction of the FLIISS and its relationship to a conceptual model of stress is presented in an article (Part I) elsewhere in this issue. In this article (Part II), reliability results and construct validity are reported for the FLIISS. The FLIISS demonstrates appropriate usefulness and content, acceptable internal consistency, and strong construct validity. Health professionals can use the instrument for collecting information that will increase their ability to identify sources of stress faced by siblings of persons with schizophrenia and develop interventions to help these siblings.
Multivariate relationships between groundwater chemistry and toxicity in an urban aquifer
Authors: Dewhurst Rachel E. , Wells N. Claire , Crane Mark , Callaghan Amanda , Connon Richard , Mather John D.
Published: November 2004

Multivariate statistical methods were used to investigate the causes of toxicity and controls on groundwater chemistry from 274 boreholes in an urban area (London) of the United Kingdom. The groundwater was alkaline to neutral, and chemistry was dominated by calcium, sodium, and sulfate. Contaminants included fuels, solvents, and organic compounds derived from landfill material. The presence of organic material in the aquifer caused decreases in dissolved oxygen, sulfate and nitrate concentrations, and increases in ferrous iron and ammoniacal nitrogen concentrations. Pearson correlations between toxicity results and the concentration of individual analytes indicated that concentrations of ammoniacal nitrogen, dissolved oxygen, ferrous iron, and hydrocarbons were important where present. However, principal component and regression analysis suggested no significant correlation between toxicity and chemistry over the whole area. Multidimensional scaling was used to investigate differences in sites caused by historical use, landfill gas status, or position within the sample area. Significant differences were observed between sites with different historical land use and those with different gas status. Examination of the principal component matrix revealed that these differences are related to changes in the importance of reduced chemical species.
Effects of nonylphenol on zooplankton in aquatic microcosms
Authors: Severin Gabriele F. , Welzl Gerhard , Jüttner Ingrid , Pfister Gerd , Schramm Karl-Werner
Published: November 2004

We investigated the effects of the endocrine disruptor nonylphenol (NP) on the zooplankton assemblages of 230 L aquatic microcosms during a four-week preapplication period, a six-week NP treatment via controlled release, and a six-week postapplication period. Zooplankton assemblage change, investigated by ordination principal response curves (PRC), was due to lower abundances of copepoda, rotifera, and cladocera. The most sensitive groups/taxa were copepoda larvae, followed by the rotifers Synchaeta spp., Polyarthra spp., and the cladocerans Daphnia longispina and Chydorus sphaericus. The mean no-observedeffect concentrations for the community (NOECCommunity) was 30 μg/L. Cladocera densities recovered during the postapplication period at all but the highest NP concentrations (maximum 120 μg/L); copepod densities did not recover at the three highest concentrations (maximum 96-120 μg/L).
Quantitative evaluation of hepatic cytochrome P4501A transcript, protein, and catalytic activity in the striped sea bream (Lithognathus mormyrus)
Authors: Tom Moshe , Shmul Merav , Shefer Edna , Chen Nir , Slor Hanoch , Rinkevich Baruch , Herut Barak
Published: November 2004

Hepatic cytochrome P4501A (CYP1A) expression was partially characterized in the striped sea bream (Lithognathus mormyrus) from the Mediterranean coast of Israel as part of the process of establishing the CYP1A gene as an environmental biomarker. Reverse transcription-competitive polymerase chain reaction, competitive enzyme-linked immunosorbent assay, and ethoxyresorufin O-deethylase (EROD) assay were used for evaluating transcript, protein, and catalytic activity levels, respectively, in absolute units. Highest elucidated transcript, protein, and catalytic activity levels were 0.264 ± SD 0.084 fmol/μg total RNA, 0.88 ± 0.52 pmol/μg total protein, and 1.11 ± 0.52 pmol resorufin/min/μg total protein, respectively, and the lower levels were 0.009 ± 0.007 fmol/μg total RNA, 0.17 ± 0.08 pmol/μg total protein, and 0.11 ± 0.06 pmol resorufin/min/μg total protein, respectively, demonstrating substantial induction potential. All alternate pairs of seven examined field samples, revealing a transcript-level ratio higher than 1.7, also demonstrated a significant difference between their transcript levels, indicating a potential to detect relatively small biomarker changes (1.7-fold) caused by environmental effects. Simultaneous triple measurements of transcript, protein, and catalytic activity were carried out in individuals from two field samples and during a 318-d decay experiment. Fish from the field samples revealed significant alternate bivariate correlation between transcript, protein, and enzymatic activity. Conflicting results were found when analyzing the decay experiment, in which both protein and catalytic activity levels decreased significantly to basal levels, in contrast to no significant change in transcript levels throughout the experiment. No significant difference was observed between males and females regarding the levels of CYP1A transcript, protein, and EROD.
Bioavailability of the organophosphorous insecticide chlorpyrifos to the suspension-feeding bivalve, Mercenaria mercenaria, following exposure to dissolved and particulate matter
Authors: Bejarano Adriana C. , Widenfalk Anneli , Decho Alan W. , Chandler G. Thomas
Published: November 2004

Under estuarine conditions, hydrophobic, hydrophobic pesticides physical/chemical partitioning into dissolved and particulate fractions of sediments. Our experimental study using 14C-chlorpyrifos (14C-CHPY) showed that sorptive associations of this common insecticide with particulate (>0.2 μm) and dissolved fractions (<0.2 μm) of sediments strongly influenced uptake, tissue absorption, and elimination in the estuarine bivalve Mercenaria mercenaria. Bivalves were fed algae mixed with particulate and dissolved fractions of 14C-CHPY-contaminated estuarine sediment particles, components of estuarine sediments (silica, humic acids), and a naturally occurring food source (phytoplankton) to quantify relative uptake, tissue absorption efficiencies, and elimination of 14C-CHPY. Measurements of 14C-CHPY tissue absorption efficiencies (AE%) indicated that particle source qualities influenced much of the insecticide bioavailability. Mean tissue AE% of 14C-CHPY associated with different particulate fractions ranged from 23 to 31%, while uptake from the dissolved/colloidal forms resulted in low (7-17%) AE%. Our data indicated that 14C-CHPY is more likely to bioaccumulate through ingestion of contaminated particulate material than through filtration/ingestion of dissolved/colloidal material. The high selectivity and digestibility of algae particles by M. mercenaria, a potentially ingested food source, may play an important role in the bioavailability of chlorpyrifos in this animal.
The use of toxicity bioassays to monitor the recovery of oiled wetland sediments
Authors: Mueller Danica C. , Bonner James S. , McDonald Susanne J. , Autenrieth Robin L. , Donnelly Kirby C. , Lee Kenneth , Doe Kenneth , Anderson Jack
Published: November 2004

Six toxicity assays were compared to determine their efficacy in assessing toxicity dynamics during a wetland bioremediation study. The toxicity bioassays used were the Microtox® 100% elutriate test, Microtox Solid Phase Test (SPT), amphipod assay, P450 reporter gene system, Toxi-ChromoPad™ test and a Salmonella/microsome assay. Oiled sediments were analyzed for toxicity in the petroleum biostimulation experiment conducted along the San Jacinto River, near Houston (TX, USA). The bioassays were evaluated for their ability to measure acute toxicity, chronic toxicity, and the mutagenic potential of amended oiled plots as compared to oiled and unoiled control plots. Amendments were diammonium phosphate alone or in combination with potassium nitrate, which served as an alternate electron acceptor. With exception of the Toxi-ChromoPad and Salmonella tests, the bioassays exhibited a significant increase in toxicity after oil application. Microtox bioassays detected significant sediment toxicity up to 29 d after oil and amendment application. The Microtox solid phase test results correlated strongly with gas chromatographymass spectrometry analyses of total target saturate and aromatic hydrocarbons. The amphipod assay detected initial toxicity with a decline to day 70, followed by a significant increase in toxicity on day 140 in plots receiving nutrient amendments, which may be in response to excessive nutrient application. Low levels of enzyme induction were observed with the P450 reporter gene system assay in all oiled sediments throughout the study, suggesting low but persistent levels of polycyclic aromatic hydrocarbons. Of the six tests, the two Microtox tests and the amphipod test showed the most potential in evaluating petroleum toxicity in wetland sediments.
Lead and stable lead isotope ratios in soil, earthworms, and bones of American woodcock (Scolopax minor) from eastern Canada
Authors: Scheuhammer Anton M. , Bond Della E. , Burgess Neil M. , Rodrigue Jean
Published: November 2004

A study to discriminate among different possible sources of elevated Pb exposure for American woodcock (Scolopax minor) in eastern Canada is described. Undamaged wing bones excised from young-of-the-year woodcock collected from several locations in southern Ontario, southern Quebec, New Brunswick, and Nova Scotia, Canada, along with soil and earthworm (Aporrectodea tuberculata and Lumbricus rubellus) samples from the same sites, were analyzed for total Pb, and stable Pb isotopes. Ignoring six soil samples with high (>60 μg/g) Pb concentration from the vicinity of Montreal (QC, Canada), the mean soil-Pb concentration for all sites combined was 19 μg/g (dry wt; n = 64), with a mean 206Pb:207Pb ratio of 1.19, values typical for uncontaminated rural soils in eastern North America. In earthworms, Pb concentrations ranged from 2.4 to 865 (μg/g [dry wt], mean = 24 μg/g). Concentrations of Pb in worms and soils were positively correlated (r = 0.71; p < 0.01), and 206Pb:207Pb ratios for worms and soils were also positively correlated (r = 0.54; p < 0.05). However, most young-of-the-year woodcock with high bone-Pb accumulation (>20 μg/g) had 206Pb:207Pb ratios substantially different from worms and soils sampled from the same areas, even though woodcock feed extensively on soil invertebrates, especially earthworms. The range of 206Pb:207Pb ratios in wing bones of woodcock with elevated Pb exposure was not consistent with exposure to environmental Pb from past gasoline combustion nor Precambrian mining wastes but was consistent with ingestion of spent Pb shotgun pellets.
Response of the zooplankton community and environmental fate of perfluorooctane sulfonic acid in aquatic microcosms
Authors: Boudreau Timothy M. , Wilson Christian J. , Cheong Woo Jay , Sibley Paul K. , Mabury Scott A. , Muir Derek C. G. , Solomon Keith R.
Published: November 2004

Little is known regarding perfluorooctane sulfonic acid (PFOS) toxicity to freshwater organisms. This field evaluation aims to assess the toxicological risk associated with exposure to PFOS across levels of biological organization. The analysis of variance study was conducted in replicate (n = 3) 12,000 L outdoor microcosms. Multivariate techniques were used to assess the response of zooplankton community structure and dynamics, as well as a floating macrophyte, Lemna gibba. The zooplankton community was significantly affected (p < 0.05) by the treatment regime given by the Monte Carlo permutations for all sampling times. A community-level no-observable-effect concentration ([NOEC]community) of 3.0 mg/L was determined for the 35-day study, however, longer term studies are recommended. The most sensitive taxonomic groups, Cladocera and Copepoda, were virtually eliminated in 30 mg/L treatments after 7 d. The 42-d 50% inhibition concentration (IC50) for L. gibba frond number was 19.1 mg/L and the NOEC was 0.2 mg/L. Furthermore, we investigated the persistence of PFOS over 285 d in microcosms under natural conditions. Perfluorooctane sulfonic acid concentration showed no drastic reduction in any treatment microcosm over the entire study period, confirming that this compound undergoes little degradation in aquatic systems. Presently, there appears to be little hazard to these freshwater organisms at reported environmental concentrations.