bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of high‐grade cervical dysplasia by the detection of p16INK4a in cell lysates obtained from cervical samples
Authors: Wentzensen Nicolas , Hampl Monika , Herkert Matthias , Reichert Anja , Trunk Marcus J. , Poremba Christopher , Ridder Ruediger , von Knebel Doeberitz Magnus
Published: October 2006

BACKGROUND.

Current cervical cancer screening approaches are based on cytology supplemented by human papillomavirus (HPV) testing in some settings. Whereas cytology is laborious and depends on the cytologists' experience, HPV testing has limited specificity when it is used to detect high‐grade lesions. A dichotomous test to identify high‐grade lesions with greater specificity may be a useful tool for cervical cancer screening. p16INK4a is a cell‐cycle regulator that has demonstrated strong overexpression in cervical precancer cells and cervical cancer induced by the deregulated expression of HPV oncogenes.

METHODS.

The authors used a sandwich enzyme‐linked immunosorbent assay (ELISA) to quantify the amount of solubilized p16INK4a protein in lysates that were prepared from cervical samples to detect high‐grade cervical lesions. In total, 187 specimens that were obtained after sampling for conventional cytology in women who attended a cervical colposcopy clinic were analyzed. Seventy‐six women underwent a biopsy, and 45 of those women showed histologically confirmed, high‐grade cervical intraepithelial neoplasia.

RESULTS.

For 76 women with biopsy‐proven diagnoses, receiver operating characteristic (ROC) analysis of different cutoff values showed an area under the ROC curve of 0.89 for the detection of high‐grade cervical dysplasia. At a cutoff value of 8 U/mL, the sensitivity of the p16INK4a ELISA for detecting high‐grade dysplastic cervical lesions was 96%.

CONCLUSIONS.

The data obtained in this study suggested that ELISA‐based quantification of solubilized p16INK4a protein may have high sensitivity for detecting cervical precancer. Further population‐based studies will be necessary to analyze the specificity and predictive values of p16INK4a protein quantification in cervical samples. Cancer 2006. © 2006 American Cancer Society.
Expression of protein kinase C‐substrate mRNAs in the basal ganglia of adult and infant macaque monkeys
Authors: Higo Noriyuki , Oishi Takao , Yamashita Akiko , Murata Yumi , Matsuda Keiji , Hayashi Motoharu
Published: October 2006

We performed in situ hybridization histochemistry on the monkey basal ganglia to investigate the mRNA localization of three protein kinase C substrates (GAP‐43, MARCKS, and neurogranin), of which expression plays a role in structural changes in neurites and synapses. Weak hybridization signals for GAP‐43 mRNA and intense signals for both MARCKS and neurogranin mRNAs were observed in the adult neostriatum. All three of the mRNAs were expressed in both substance P‐positive direct pathway neurons and enkephalin‐positive indirect pathway neurons. In the nucleus accumbens, the hybridization signals for the three mRNAs were weaker than those in the neostriatum. Double‐label in situ hybridization histochemistry in the neostriatum revealed that GAP‐43 and neurogranin mRNAs were expressed in a subset of MARCKS‐positive neurons. While intense hybridization signals for MARCKS mRNA were observed in all of the other basal ganglia regions such as the globus pallidus, substantia innominata, subthalamic nucleus, and substantia nigra, intense signals for GAP‐43 mRNA were restricted to the substantia innominata and substantia nigra pars compacta. No signal for neurogranin mRNA was observed in the basal ganglia regions outside the neostriatum and the nucleus accumbens. These results indicate that the protein kinase C substrates are abundant in some specific connections in cortico‐basal ganglia circuits. Developmental analysis showed that the expression level in the putamen and nucleus accumbens, but not in the caudate nucleus, was higher in the infant than in the adult, suggesting that synaptic maturation in the caudate nucleus occurs earlier than that in the putamen and nucleus accumbens. J. Comp. Neurol. 499:662–676, 2006. © 2006 Wiley‐Liss, Inc.
Estradiol‐induced modulation of estrogen receptor‐β and GABA within the adult neocortex: A potential transsynaptic mechanism for estrogen modulation of BDNF
Authors: Blurton‐Jones Mathew , Tuszynski Mark H.
Published: October 2006

Estrogen influences brain‐derived neurotrophic factor (BDNF) expression in the neocortex. However, BDNF‐producing cortical neurons do not express detectable levels of nuclear estrogen receptors; instead, the most abundant cortical nuclear estrogen receptor, ER‐β, is present in GABAergic neurons, prompting us to test the hypothesis that estrogen effects on BDNF are mediated via cortical inhibitory interneurons. Adult female ovariectomized rats were provided acute estrogen replacement and the number of cortical GABA, ER‐β, and ER‐β/GABA double‐labeled neurons was examined. Within 48 hours of injection of 17‐β‐estradiol, the number of perirhinal neurons double‐labeled for ER‐β/GABA was reduced by 28% (P < 0.01 compared to vehicle‐treated ovariectomized controls), and all cells expressing detectable levels of GABA were reduced by 19% (P < 0.01). To investigate potential relationships between estrogen receptors, GABAergic neurons, and BDNF‐expressing cells, brain sections were double‐ or triple‐labeled for ER‐β, GABAergic, and BDNF immunomarkers. The findings indicated that ER‐β‐bearing inhibitory neurons project onto other GABAergic neurons that lack nuclear estrogen receptors; these inhibitory neurons in turn innervate BDNF‐expressing excitatory cells. High estrogen states reduce cortical GABA levels, presumably releasing inhibition on BDNF‐expressing neurons. This identifies a putative two‐step transsynaptic mechanism whereby estrogen availability modulates expression of inhibitory transmitters, resulting in increased BDNF expression. J. Comp. Neurol. 499:603–612, 2006. © 2006 Wiley‐Liss, Inc.
Clinical psychology service provision and ethnic diversity within the UK: a review of the literature
Authors: Williams Patricia E. , Turpin Graham , Hardy Gillian
Published: October 2006

There is substantial evidence to suggest that clinical psychology services are failing to meet the psychological and clinical needs of people from minority ethnic groups. This paper reviews current knowledge and understanding of factors that may be contributing to this, by examining the diversity of clinical psychology service provisions for minority ethnic groups in the United Kingdom (UK). Research that focuses on the poor utilization of clinical psychology services by minority ethnic groups is identified, and this is related to the limitations offered by mainstream psychological services. References to developments from abroad are also included where they enhance understanding of the current situation affecting minority ethnic groups in the UK. The findings show that minority ethnic groups are generally marginalized and excluded from mainstream clinical psychology services on a number of different levels. These are often influenced by referral conventions, professional misunderstandings of psychological distress and an over‐reliance on ethnocentric and eurocentric conceptual frameworks. Cultural factors are also implicated. This review illustrates that the profession needs to be more considerate in its provision of services for minority ethnic users and indelible steps taken to increase the accessibility and credibility of clinical psychology services to Black and other minority ethnic groups. Copyright © 2006 John Wiley & Sons, Ltd.
Two‐dimensional morphogen gradient in Xenopus: Boundary formation and real‐time transduction response
Authors: Kinoshita T. , Jullien J. , Gurdon J.B.
Published: October 2006

Morphogen gradients play an important role in pattern formation in embryo. However, the interpretation of position in a morphogen gradient is not well understood. Because it is hard to analyze morphogen gradients especially in opaque embryos such as those of Xenopus, it is necessary to fix and section the embryo, thereby eliminating the possibility of real‐time observation, and making more difficult the interpretation of events that take place in three dimensions. We describe here a two‐dimensional preparation of cells from a Xenopus blastula animal cap, in which an activin concentration gradient appears to be formed and interpreted at the same rate and in the same way as in normal embryos. We use two‐dimensional preparations of this kind to contribute the following new information about gradient formation and interpretation in embryo. We determine the dynamics of formation of an activin activity gradient in real time. We demonstrate that this gradient is established by diffusion of activin through intercellular space and does not require internalization of receptor or ligand. We also show that the generation of a boundary of gene expression depends on the interpretation, rather than a change of composition, of the concentration gradient. Developmental Dynamics 235:3189–3198, 2006. © 2006 Wiley‐Liss, Inc.
Open‐tubular capillary columns with a porous layer of monolithic polymer for highly efficient and fast separations in electrochromatography
Authors: Eeltink Sebastiaan , Svec Frantisek , Fréchet Jean M. J.
Published: October 2006

Open‐tubular columns for CEC separations having inner‐wall coated with a thin layer of porous monolithic polymer have been studied. A two‐step process including (i) UV‐initiated polymerization leading to a layer of porous poly(butyl methacrylate‐co‐ethylene dimethacrylate), and (ii) UV‐initiated grafting of ionizable monomers appear to be well suited for the preparation of these columns. The thickness of the porous polymer layer is controlled by the percentage of monomers in the polymerization mixture and/or length of the irradiation time. The layer thickness significantly affects retention, efficiency, and resolution in open‐tubular CEC. Under optimized conditions, column efficiencies up to 400 000 plates/m can be achieved. Use of higher temperature and application of pressure enables a significant acceleration of the open‐tubular CEC separations.
Dynamic unfolding of a regulatory subunit of cAMP‐dependent protein kinase by capillary electrophoresis: Impact of cAMP dissociation on protein stability
Authors: Gavina Jennilee M. A. , Das Rahul , Britz‐McKibbin Philip
Published: October 2006

Characterization of the unfolding dynamics of a recombinant type IA regulatory subunit (RIα) of cyclic adenosine monophosphate (cAMP)‐dependent protein kinase (cAPK) was examined by CE with UV detection. Electrophoretic separation of RIα by CE in a buffer devoid of cAMP resulted in rapid dissociation of the complex from the original sample due to the high negative mobility of the ligand relative to receptor. This process enabled in‐capillary generation of cAMP‐stripped RIα, which was used to estimate the apparent dissociation constant (Kd) of 0.6 ± 0.2 μM. A comparison of RIα dynamic unfolding processes with urea denaturation was performed by CE with (i.e., RIα–cAMP) and without (i.e., cAMP‐stripped RIα) excess cAMP in the buffer during electromigration. The presence of cAMP in the buffer confirmed greater stabilization of the protein, as reflected by a higher standard free energy change (ΔGU°) of 10.1 ± 0.5 kcal·mol+1 and greater cooperativity in unfolding (m) of −2.30 ± 0.11 kcal·mol−1M−1. CE offers a rapid, yet versatile platform for probing the thermodynamics of cAPK and other types of receptor–ligand complexes in free solution.
Modulation of connexin expression and gap junction communication in astrocytes by the gram‐positive bacterium S. aureus
Authors: Esen Nilufer , Shuffield Debbie , SYED Mohsin MD. , Kielian Tammy
Published: October 2006

Gap junctions establish direct intercellular conduits between adjacent cells and are formed by the hexameric organization of protein subunits called connexins (Cx). It is unknown whether the proinflammatory milieu that ensues during CNS infection with S. aureus, one of the main etiologic agents of brain abscess in humans, is capable of eliciting regional changes in astrocyte homocellular gap junction communication (GJC) and, by extension, influencing neuron homeostasis at sites distant from the primary focus of infection. Here we investigated the effects of S. aureus and its cell wall product peptidoglycan (PGN) on Cx43, Cx30, and Cx26 expression, the main Cx isoforms found in astrocytes. Both bacterial stimuli led to a time‐dependent decrease in Cx43 and Cx30 expression; however, Cx26 levels were elevated following bacterial exposure. Functional examination of dye coupling, as revealed by single‐cell microinjections of Lucifer yellow, demonstrated that both S. aureus and PGN inhibited astrocyte GJC. Inhibition of protein synthesis with cyclohexamide (CHX) revealed that S. aureus directly modulates, in part, Cx43 and Cx30 expression, whereas Cx26 levels appear to be regulated by a factor(s) that requires de novo protein production; however, CHX did not alter the inhibitory effects of S. aureus on astrocyte GJC. The p38 MAPK inhibitor SB202190 was capable of partially restoring the S. aureus‐mediated decrease in astrocyte GJC to that of unstimulated cells, suggesting the involvement of p38 MAPK‐dependent pathway(s). These findings could have important implications for limiting the long‐term detrimental effects of abscess formation in the brain which may include seizures and cognitive deficits. © 2006 Wiley‐Liss, Inc.
The case against JIVE
Authors: Davidson Russell , MacKinnon James G.
Published: October 2006

We perform an extensive series of Monte Carlo experiments to compare the performance of two variants of the ‘jackknife instrumental variables estimator’, or JIVE, with that of the more familiar 2SLS and LIML estimators. We find no evidence to suggest that JIVE should ever be used. It is always more dispersed than 2SLS, often very much so, and it is almost always inferior to LIML in all respects. Interestingly, JIVE seems to perform particularly badly when the instruments are weak. Copyright © 2006 John Wiley & Sons, Ltd.
Estimation and comparison of treasury auction formats when bidders are asymmetric
Authors: Armantier Olivier , SbaÏ Erwann
Published: October 2006

The structural parameters of a share‐auction model accounting for asymmetries across bidders, as well as supply uncertainty, are estimated with a sample of French Treasury auctions. We find evidence of both informational and risk aversion asymmetries across bidders. A counter‐factual analysis also suggests that, in the context of the French Treasury auctions, a shift from the discriminatory to the uniform‐price format would simultaneously benefit the French Treasury and the auctions' participants. Copyright © 2006 John Wiley & Sons, Ltd.
Wealth dynamics: reducing noise in panel data
Authors: Hill Daniel H.
Published: October 2006

Although the asset data from the Health and Retirement Study (HRS) is of very high quality, there is sufficient noise to frustrate attempts to study saving behaviour by examining wave‐to‐wave change in wealth. In this research, we attempt to reduce noise by means of reactive‐dependent interviewing in which respondents with large inexplicable changes in assets between 1998 and 2000 are called back by HRS interviewers, presented with their prior reports and asked to reconcile the data. We achieved reconciliation for 1255 households (2479 net‐worth components) and, as a result, the variance in measured change for the entire sample of 11,583 households with the same financial respondents in both waves was cut in half. The empirical validity of the data also appears to have been improved. The correlation of gross change in net worth and income, for instance, increased from an insignificant negative to a highly significant positive value. Although reconciliation of large asset changes marginally improves the goodness of fit of multivariate models, there remains sufficient noise in the asset‐change data to require analysts to employ additional methods to reduce the influence of outliers. Copyright © 2006 John Wiley & Sons, Ltd.
Assessing the effects of measurement errors on the estimation of production functions
Authors: Ornaghi Carmine
Published: October 2006

This article explores to what extent the poor results that are often found when estimating parameters of production functions can be attributed to measurement errors, due to the use of common price deflators across firms. Because of the lack of detailed micro‐economic data, econometricians have to rely on industry‐wide deflators when computing outputs and intermediate inputs. A unique feature of the longitudinal data used in this paper is that it reports firm‐level prices. This allows for a comparative assessment of production function parameters where the outputs and intermediate inputs are computed using both firm‐specific prices and industry‐wide deflators. The empirical results presented in this paper show that the use of common deflators across firms leads to lower scale estimates, mainly because of a large downward bias in the estimated coefficients for labour. Copyright © 2006 John Wiley & Sons, Ltd.
Introduction to the special issue: Youth mentoring: Bridging science with practice
Authors: DuBois David L. , Rhodes Jean E.
Published: October 2006

Initiatives to promote mentoring relationships in the lives of young people have become immensely popular in recent years. Programs with this aim now number well into the thousands and benefit from significant levels of governmental, corporate, and philanthropic support. The research base that is necessary to inform the practice of mentoring, by comparison, has lagged behind. To address the field's need for a stronger scientific foundation, MENTOR/National Mentoring Partnership convened the National Research Summit on Mentoring in 2003. A policy brief that resulted from the summit identified several priority areas for future research on youth mentoring, as well as strategic mechanisms to support this work. This special issue features reports from working groups at the summit that were organized around the following themes: evaluation and research methodology, relationships, programs, contexts, special populations, developmental and cultural perspectives, and community organizing and advocacy. Collectively, the reports highlight the need for research to clarify a wide range of important theoretical and pragmatic issues in efforts to promote effective mentoring of youth. © 2006 Wiley Periodicals, Inc.
Research methodology and youth mentoring
Authors: DuBois David L. , Doolittle Fred , Yates Brian T. , Silverthorn Naida , Tebes Jacob Kraemer
Published: October 2006

Mentoring programs for youth have grown tremendously in popularity in recent years and in many important respects reflect core principles of community psychology. Mentoring of youth is a complex phenomenon, however, with a range of significant processes occurring at the levels of individual youth and their mentors, youth–mentor relationships and other interpersonal systems, programs, and the larger policy context. The research methods used to study youth mentoring need to be well suited to capturing this complexity. In this article, we argue, furthermore, that investigations of youth mentoring relationships and programs should be tailored to address concerns associated with each major phase of the intervention research cycle (i.e., preintervention, intervention, and preventive service systems research). Existing research pertinent to these differing phases frequently has not employed state‐of‐the‐art methodology in the areas of sampling, design, assessment, and analysis. We also find that there are important gaps in the types of research conducted, and that in many instances, needed linkages across phases of the research cycle are lacking. Recommendations for strengthening future research on youth mentoring are discussed. © 2006 Wiley Periodicals, Inc.
Positive youth development, willful adolescents, and mentoring
Authors: Larson Reed
Published: October 2006

This article describes positive youth development as a process in which young people's capacity for being motivated by challenge energizes their active engagement in development. The first part of the article discusses the conditions under which this motivation is activated and considers obstacles to its activation in daily life. The second part discusses ways in which caring adults, including mentors, can support this process of positive development. Several frameworks that provide models of how adults can provide needed structure and guidance while supporting youth's development as agents of their own growth are discussed. © 2006 Wiley Periodicals, Inc.
A model for the influence of mentoring relationships on youth development
Authors: Rhodes Jean E. , Spencer Renée , Keller Thomas E. , Liang Belle , Noam Gil
Published: October 2006

Anecdotal reports of the protective qualities of mentoring relationships for youth are corroborated by a growing body of research. What is missing, however, is research on the processes by which mentors influence developmental outcomes. In this article, we present a conceptual model of the mentoring process along with a delineation of some of the current research on what makes for more effective mentoring relationships. A set of recommendations for future research is offered. © 2006 Wiley Periodicals, Inc.
Mentoring programs: A framework to inform program development, research, and evaluation
Authors: Karcher Michael J. , Kuperminc Gabriel P. , Portwood Sharon G. , Sipe Cynthia L. , Taylor Andrea S.
Published: October 2006

As mentoring programs have proliferated, considerable variation in approaches to programmatic mentoring has emerged. Concomitant confusion exists about the context, structure, and goals that constitute mentoring as a distinct intervention. This article presents a brief summary of what is currently known about different approaches to mentoring and proposes a framework that identifies both the common and the specific elements among different youth mentoring approaches. Rather than focusing solely on the participants and contexts of mentoring programs, such as peer‐ or school‐based mentoring, as the key elements that differentiate programs, the authors suggest that more fruitful program development and research will result from a closer examination of the context, structure, and goals of programs, as well as of three critical program elements: content, infrastructure, and dosage. To understand better how and under what conditions mentoring works, program developers and researchers should test hypotheses regarding the influences of these program elements based on theory‐driven expectations about the interrelationships among proximal, enabling, and distal outcomes of mentoring programs. © 2006 Wiley Periodicals, Inc.
Community contexts for mentoring
Authors: Hamilton Stephen F. , Agnes Hamilton Mary , Hirsch Barton J. , Hughes Jan , King Jacqueline , Maton Kenneth
Published: October 2006

Mentoring programs attempt to foster a relationship that is too often missing from the lives of disadvantaged children and youth. However, in view of both the power and the limitations of mentoring programs, it is important to understand how mentoring occurs naturally. Assuming an ecological perspective, we examine mentoring in four contexts: classrooms, youth development organizations, work and service‐learning, and faith‐ based organizations. Although none has been studied in sufficient depth, and no research has been found on natural mentoring in faith‐based organizations, available evidence indicates that such mentoring adds to young people's intellectual, psychological and emotional, social, and, to a lesser extent, physical assets. This review poses many questions for future research, including fundamental ones about the prevalence of mentoring in these contexts, the circumstances in which it arises, and its risks and benefits. Nonetheless, the evidence is sufficient to encourage practitioners to promote mentoring relationships of youth and adults in all of these contexts. © 2006 Wiley Periodicals, Inc.
Anatomy of the frontal gland and ultramorphology of the frontal tube in the soldier caste of species of Nasutitermitinae (Isoptera, Termitidae)
Authors: A. Santos Conceicao , M. Costa‐Leonardo Ana
Published: October 2006

All termite species (Isoptera) are eusocial. These insects live in societies where the division of labor is a predominant characteristic, conditioned by the presence of castes with different morphology, ontogeny, and development. The soldier caste is unique among social insects and it is responsible for colony defense. Soldiers belonging to the Nasutitermitinae subfamily are very peculiar, since they may be polymorphic and present a nasus in addition to either developed or vestigial mandibles. The defensive secretions of soldiers of the neotropical Nasutitermitinae have been the aim of several chemical studies, but few data exist concerning the anatomy and histology of the exocrine glands. This article presents a comparative study on the anatomy of the frontal gland of soldiers of several Nasutitermitinae species:Syntermes dirus(Burmeister),Syntermes nanus(Constantino),Constrictotermes cyphergaster(Silvestri),Nasutitermes corniger(Motschulsky) andVelocitermes heteropterus(Silvestri), with emphasis on the ultramorphology and ultrastructure of the frontal tube. Microsc. Res. Tech., 2006. © 2006 Wiley‐Liss, Inc.
The tri‐segmented limbs of therian mammals: kinematics, dynamics, and self‐stabilization—a review
Authors: Fischer Martin S. , Blickhan Reinhard
Published: October 2006

The evolution of therian mammals is to a large degree marked by changes in their motion systems. One of the decisive transitions has been from the sprawled, bi‐segmented to the parasagittal, tri‐segmented limb. Here, we review aspects of the tri‐segmented limb in locomotion which have been elucidated in our research groups in the last 10 years. First, we report the kinematics of the tri‐segmented therian limb from mouse to elephant in order to explore general principles of the therian limb configuration and locomotion. Torques will be reported from a previous paper (Witte et al., 2002. J Exp Biol 205:1339–1353) for a better understanding of the anti‐gravity work of all limb joints. The stability of a limb in z‐configuration will be explained and its advantage with respect to other potential solutions from modeling will be discussed. Finally, we describe how the emerging concept of self‐stability can be explained for a tri‐segmented leg template and how it affects the design of the musculoskeletal system and the operation of legs during locomotion. While locomotion has been considered as mainly a control problem in various disciplines, we stress the necessity to reduce control as much as possible. Central control can be cheap if the limbs are “intelligent” by means of their design. Gravity‐induced movements and self‐stability seem to be energy‐saving mechanisms. J. Exp. Zool. 305A, 2006. © 2006 Wiley‐Liss, Inc.
Analysis of strategies to improve cost effectiveness of blood cultures
Authors: Zwang Oren , Albert Richard K.
Published: October 2006

BACKGROUND

Approximately 90% of all blood cultures grow no organisms (ie, are true negatives), and 5% are thought to represent contaminants (ie, are false positives). The cost effectiveness of blood cultures could therefore be improved by developing rules that safely decreased the number of cultures drawn from patients with a low likelihood of having bacteremia and/or by improving the process of obtaining cultures, thereby decreasing the number of contaminants. We analyzed the potential effects of these two approaches.

METHODS

We annualized the hospital costs and lengths of stay for patients with true‐negative and false‐positive blood cultures from a retrospective analysis of 939 sets of cultures drawn in January 2002.

RESULTS

Of the 939 blood culture sets, 816 (87%) were true negatives and generated annualized costs of approximately $750,000. Although only 56 (6%) of the blood culture sets were false positives, they resulted in annualized costs of $1.4‐$1.8 million and added an estimated 1450‐2200 extra hospital days/year.

CONCLUSIONS

Despite there being nearly 15 times as many true‐negative blood cultures as false positive ones, far greater improvements in resource utilization would result from reducing the number of contaminated blood cultures than by reducing the number of true negatives. The potential savings from this approach are of sufficient magnitude to justify investing considerable resources to attaining this goal. Journal of Hospital Medicine 2006;1:272–276. © 2006 Society of Hospital Medicine.
Magnetic resonance angiography reveals therapeutic enlargement of collateral vessels induced by VEGF in a murine model of peripheral arterial disease
Authors: Greve Joan M. , Chico Timothy J. , Goldman Hope , Bunting Stuart , Peale Franklin V. , Daugherty Ann , van Bruggen Nicholas , Williams Simon P.
Published: October 2006

Purpose

To quantify spontaneous and therapeutic arteriogenesis in vivo in a murine model of peripheral arterial disease using magnetic resonance angiography.

Materials and Methods

Male, 8–12‐week‐old, C57/BL6 mice underwent femoral artery ligation; 21 days later, 2 mg/kg recombinant murine VEGF165, formulated for slow release, was injected into the ipsilateral gastrocnemius. The spontaneous (following ligation) and therapeutic (following vascular endothelial growth factor (VEGF)) formation of collateral vessels was quantified using 3D magnetic resonance angiography on a small‐bore 4.7T system. Therapeutically induced angiogenesis and blood flow were quantified using an in situ anti‐platelet endothelial cell adhesion molecule (PECAM) 1 radioimmunoassay and radiolabeled microsphere deposition, respectively.

Results

Spontaneous arteriogenesis was visible in all animals five days after ligation. VEGF treatment doubled the arteriogenic response five days after treatment compared to vehicle (cross‐sectional area of vessels: 0.96 vs. 0.46 mm2,P< 0.01). VEGF also induced angiogenesis (PECAM1 levels 191% of vehicle,P< 0.05) and increased blood flow specific to the injection site (57 vs. 7 mL/minute/100 g,P< 0.05).

Conclusion

The presented methodology allowed in vivo quantification of spontaneous arteriogenesis in a murine model of peripheral arterial disease and demonstrated that therapeutic enlargement of collateral vessels is possible with VEGF. J. Magn. Reson. Imaging 2006. © 2006 Wiley‐Liss, Inc.
Asymptotic domination of operators on Köthe function spaces and convergence of sequences
Authors: Sánchez Pérez E. A.
Published: October 2006

We study the asymptotic behavior of Maurey–Rosenthal type dominations for operators on Köthe function spaces which satisfy norm inequalities that define weak q ‐concavity properties. In particular, we define and study two new classes of operators that we call α ‐almost q ‐concave and qα ‐concave operators (1 ≤ q < ∞, 0 ≤ α < 1). We also provide a factorization theorem through real interpolation spaces for qα ‐concave operators. We also discuss some direct consequences of these results regarding the strong convergence of sequences on Köthe function spaces. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Longitudinal study of the motor response to levodopa in Parkinson's disease
Authors: Clissold Benjamin G. , McColl Craig D. , Reardon Katrina R. , Shiff Mark , Kempster Peter A.
Published: October 2006

In this prospective study of 34 patients with Parkinson's disease, measurements of the short duration levodopa motor response have been performed in defined off states at 3 yearly intervals over a mean period of 11.4 years from the point of commencement of levodopa treatment. Twenty‐two patients were still available for study; 10 had died and 2 were lost to follow‐up. The levodopa motor response amplitude increases over the first 5 years of treatment, and thereafter, on and off scores worsen in parallel with conservation of the response. Patients who developed motor fluctuations within the first 5 years of treatment had, on average, a stronger response to levodopa with significantly better on phase motor function (P = 0.003). Although the proportion of “midline” motor disability (affecting gait, balance, and cranial motor function) increases with time, these deficits do not actually become unresponsive to levodopa. Patients who developed dementia had a significantly more rapid decline in motor function. The latest graph of serial scores for the whole cohort shows an upward curving or exponential increase in motor disability after the first decade of treatment. Applying a notional untreated disability line to this graph—an estimate of the disability that would have accrued if drugs had never been given—we suggest that the long‐duration response to levodopa eventually runs down with disease progression. © 2006 Movement Disorder Society
Associations between family history of Parkinson's disease and dementia and risk of dementia in Parkinson's disease: A community‐based, longitudinal study
Authors: Kurz Martin Wilhelm , Larsen Jan Petter , Kvaloy Jan Terje , Aarsland Dag
Published: October 2006

Dementia is common in patients with Parkinson's disease (PDD). The etiology of PDD is still unclear, but exciting advances have been made in discovering pathogenetic components in Parkinson's disease (PD), implicating the role of genetic factors. It is, however, still controversial whether genetic factors also contribute to the development of dementia in PD. Thus, we investigated the association between development of dementia and a positive family history of PD or dementia in a community‐based study of PD in Rogaland County, Norway (n = 219). The patients were followed prospectively with neurological and neuropsychological assessments. Dementia was more common in patients with a strong family association of PD (first‐degree relatives > second‐degree relatives > no family history; P < 0.05). However, time to dementia did not differ between the two groups. No associations between dementia in PD and familial occurrence of dementia could be shown. Further studies with larger samples are needed to explore a possible relationship between a family history of PD and development of dementia in PD and its potential pathogenetic mechanisms. © 2006 Movement Disorder Society
Chemodosimetry of in vivo tumor liposomal drug concentration using MRI
Authors: Viglianti Benjamin L. , Ponce Ana M. , Michelich Charles R. , Yu Daohai , Abraham Sheela A. , Sanders Linda , Yarmolenko Pavel S. , Schroeder Thies , MacFall James R. , Barboriak Daniel P. , Colvin O. Michael , Bally Marcel B. , Dewhirst Mark W.
Published: October 2006

Effective cancer chemotherapy depends on the delivery of therapeutic drugs to cancer cells at cytotoxic concentrations. However, physiologic barriers, such as variable vessel permeability, high interstitial fluid pressure, and heterogeneous perfusion, make it difficult to achieve that goal. Efforts to improve drug delivery have been limited by the lack of noninvasive tools to evaluate intratumoral drug concentration and distribution. Here we demonstrate that tumor drug concentration can be measured in vivo using T1‐weighted MRI, following systemic administration of liposomes containing both drug (doxorubicin (DOX)) and contrast agent (manganese (Mn)). Mn and DOX concentrations were calculated using T1 relaxation times and Mn:DOX loading ratios, as previously described. Two independent validations by high‐performance liquid chromatography (HPLC) and histologic fluorescence in a rat fibrosarcoma (FSA) model indicate a concordant linear relationship between DOX concentrations determined using T1 and those measured invasively. This method of imaging exhibits potential for real‐time evaluation of chemotherapeutic protocols and prediction of tumor response on an individual patient basis. Magn Reson Med, 2006. © 2006 Wiley‐Liss, Inc.
Microvessel density estimation in the human brain by means of dynamic contrast‐enhanced echo‐planar imaging
Authors: Jensen Jens H. , Lu Hanzhang , Inglese Matilde
Published: October 2006

Animal studies have shown that in vivo estimates of microvessel density in the brain may be obtained from an MRI‐measurable index (Q) provided that a sufficiently high dose of an intravascular paramagnetic contrast agent is employed. Q is determined from the shifts in the transverse relaxation rates induced by the contrast agent, and a high dose is required for the validity of analytic expressions relating Q to the microvessel density. However, the steady‐state imaging techniques used in these prior investigations are not appropriate for humans, as the required contrast agent dose is too large. Here results of a pilot study with three subjects are reported. The results suggest that reliable Q measurements can be performed in the human brain at 1.5 T by using an interleaved spin‐echo (SE)/gradient‐echo (GE) echo‐planar imaging (EPI) sequence and a bolus injection of a triple dose of Gd‐DTPA. Lower‐ and upper‐bound estimates for the microvessel density were derived from the Q‐values, and were found to be in reasonable accord with previously cited values determined by histology. Magn Reson Med, 2006. © 2006 Wiley‐Liss, Inc.
T2 measurement and quantification of glutamate in human brain in vivo
Authors: Choi Changho , Coupland Nicholas J. , Bhardwaj Paramjit P. , Kalra Sanjay , Casault Colin A. , Reid Kim , Allen Peter S.
Published: October 2006

The proton NMR transverse relaxation time T2 of glutamate (Glu) in human brain was measured by means of spectrally selective refocusing at 3.0 T in vivo. An 81.4‐ms‐long dual‐band Gaussian 180° RF pulse, designed for refocusing at 2.35 and 3.03 ppm, was employed within point‐resolved spectroscopy (PRESS) to generate the Glu C4‐proton target multiplet and the total creatine (tCr) singlet. Six optimal echo times (TEs) between 128 and 380 ms were selected from numerical analysis of the filtering performance for effective detection of the Glu signal with minimal contamination from glutamine (Gln), N‐acetylaspartate (NAA), and glutathione (GSH). The magnetization of Glu and tCr was extracted from spectral fitting of experimental and calculated spectra. Apparent T2 values of Glu and tCr were estimated as 201 ± 18 and 164 ± 12 ms for the medial prefrontal (PF) cortex, and 198 ± 22 and 169 ± 15 ms (mean ± SD, N = 5) for the left frontal (LF) cortex, respectively. With water segmentation data, the magnetization values of Glu and tCr of the two adjacent voxels, calculated from the T2 values and spectra following the thermal equilibrium magnetization, were combined to give the Glu and tCr concentrations as 10.37 ± 1.06 and 8.87 ± 0.56 mM for gray matter (GM), and 5.06 ± 0.57 and 5.16 ± 0.45 mM (mean ± SD, N = 5) for white matter (WM), respectively. Magn Reson Med, 2006. © 2006 Wiley‐Liss, Inc.
Three‐dimensional prepolarized magnetic resonance imaging using rapid acquisition with relaxation enhancement
Authors: Matter Nathaniel I. , Scott Greig C. , Venook Ross D. , Ungersma Sharon E. , Grafendorfer Thomas , Macovski Albert , Conolly Steven M.
Published: October 2006

Prepolarized MRI (PMRI) with pulsed electromagnets has the potential to produce diagnostic quality 0.5‐ to 1.0‐T images with significantly reduced cost, susceptibility artifacts, specific absorption rate, and gradient noise. In PMRI, the main magnetic field cycles between a high field (Bp) to polarize the sample and a homogeneous, low field (B0) for data acquisition. This architecture combines the higher SNR of the polarizing field with the imaging benefits of the lower field. However, PMRI can only achieve high SNR efficiency for volumetric imaging with 3D rapid imaging techniques, such as rapid acquisition with relaxation enhancement (RARE) (FSE, TSE), because slice‐interleaved acquisition and longitudinal magnetization storage are both inefficient in PMRI. This paper demonstrates the use of three techniques necessary to achieve efficient, artifact‐free RARE in PMRI: quadratic nulling of concomitant gradient fields, electromotive force cancelation during field ramping, and phase compensation of CPMG echo trains. This paper also demonstrates the use of 3D RARE in PMRI to achieve standard T1 and fat‐suppressed T2 contrast in phantoms and in vivo wrists. These images show strong potential for future clinical application of PMRI to extremity musculoskeletal imaging and peripheral angiography. Magn Reason Med, 2006. © 2006 Wiley‐Liss.Inc.
Risk factors for extraocular relapse following enucleation after failure of chemoreduction in retinoblastoma
Authors: Chantada Guillermo L. , Dunkel Ira J. , Antoneli Celia B.G. , de Dávila María T.G. , Arias Victor , Beaverson Katherine , Fandiño Adriana C. , Chojniak Martha , Abramson David H.
Published: October 2006

Objective

To assess the outcome and determine risk factors for extraocular relapse in patients with retinoblastoma who had been enucleated after failure of chemoreduction.

Methods

Retrospective study (1995–2002) at three institutions. Pathological risk factors (PRF) were defined as invasion of the anterior segment, choroid, post‐laminar optic nerve, subarachnoid space, or sclera according to the local pathology report. Extraocular relapse was defined as an event.

Results

One hundred twenty‐two patients were included (17 had bilateral enucleation). Chemoreduction included vincristine, carboplatin, and etoposide (n = 80, 65.6%), vincristine, and carboplatin (n = 17, 13.9%), or carboplatin (n = 25, 20.5%). Thirty‐five also received external beam radiotherapy (28.7%). PRF included: 39 with choroidal involvement, 9 with anterior segment, 9 with scleral, and 2 with post‐laminar optic nerve with subarachnoid invasion. Adjuvant chemotherapy was given to eight patients (6.5%) because of scleral invasion. Four patients had an extraocular relapse after enucleation, two of whom survive after intensive treatment including stem cell rescue. Five‐year probability of event‐free survival is 0.96. Only scleral invasion and bilateral enucleation were significantly associated with extraocular relapse.

Conclusions

The risk of extraocular relapse is low after enucleation following failure of chemoreduction. Patients who underwent bilateral enucleation and those with scleral invasion are at higher risk of extraocular relapse. Pediatr Blood Cancer 2007;49:256–260. © 2006 Wiley‐Liss, Inc.
De‐investment in work and non‐normative personality trait change in young adulthood
Authors: Roberts Brent W. , Walton Kate , Bogg Tim , Caspi Avshalom
Published: October 2006

The present study investigated the relationship between experiences of de‐investment in work and change in personality traits in an 8‐year longitudinal study of young adults (N = 907). De‐investment was defined as participating in activities that run counter to age‐graded norms for acceptable behaviour. De‐investment in work was operationalised with a measure of counterproductive work behaviours (CWBs), which included actions such as stealing from the work place, malingering and fighting with co‐workers. CWBs were used to predict changes in personality traits from age 18 to age 26. Consistent with hypotheses, greater amounts of CWB was associated with changes in the broad trait domains of negative emotionality and constraint. Copyright © 2006 John Wiley & Sons, Ltd.
Paranormal beliefs: their dimensionality and correlates
Authors: Lindeman Marjaana , Aarnio Kia
Published: October 2006

Lack of conceptual clarity and multivariate empirical studies has troubled research on superstitious, magical and paranormal beliefs. We defined paranormal beliefs as beliefs in physical, biological or psychological phenomena that feature core ontological properties of another ontological category. The aim was to bring together a range of beliefs and their potential correlates, to analyse whether the beliefs form independent subsets, and to test a structural model of the beliefs and their potential correlates. The results (N = 3261) showed that the beliefs could be best described by one higher‐order factor. There were also four lower‐order factors of paranormal beliefs but their explanatory power was low. Magico‐religious beliefs were best explained by high intuitive thinking, a humanistic world view and low analytical thinking. Copyright © 2006 John Wiley & Sons, Ltd.
Lifespan development of personality and developmental outcome domains
Authors: van Lieshout Cornelis F. M.
Published: October 2006

Commenting on the papers of this special issue, an evolutionary and lifespan perspective was taken. A model was proposed of parallels in the trajectories of the development of personality and developmental outcome domains across the life course. Despite findings of mean‐level change in personality development, the hypothesis was propagated of absence of normative change in personality development and developmental outcome domains across the life course, combined with the preservation of stable individual differences for the majority of people and unstable individual differences for minorities. The role of the role of personality in psychological processes involved in problem solving on developmental outcome domains needs further systematic study. Copyright © 2006 John Wiley & Sons, Ltd.
Novel approach for α‐helical topology prediction in globular proteins: Generation of interhelical restraints
Authors: McAllister S. R. , Mickus B. E. , Klepeis J. L. , Floudas C. A.
Published: October 2006

The protein folding problem represents one of the most challenging problems in computational biology. Distance constraints and topology predictions can be highly useful for the folding problem in reducing the conformational space that must be searched by deterministic algorithms to find a protein structure of minimum conformational energy. We present a novel optimization framework for predicting topological contacts and generating interhelical distance restraints between hydrophobic residues in α‐helical globular proteins. It should be emphasized that since the model does not make assumptions about the form of the helices, it is applicable to all α‐helical proteins, including helices with kinks and irregular helices. This model aims at enhancing the ASTRO‐FOLD protein folding approach of Klepeis and Floudas (Journal of Computational Chemistry 2003;24:191–208), which finds the structure of global minimum conformational energy via a constrained nonlinear optimization problem. The proposed topology prediction model was evaluated on 26 α‐helical proteins ranging from 2 to 8 helices and 35 to 159 residues, and the best identified average interhelical distances corresponding to the predicted contacts fell below 11 Å in all 26 of these systems. Given the positive results of applying the model to several protein systems, the importance of interhelical hydrophobic‐to‐hydrophobic contacts in determining the folding of α‐helical globular proteins is highlighted. Proteins 2006. © 2006 Wiley‐Liss, Inc.