bluuebunny/crossref_metadata_2025 huggingface dataset:
Régis Debray and Mediation Studies, or How Does an Idea Become a Material Force?
Authors: Vandenberghe Frédéric
Published: April 2007

This article presents an outline of Régis Debray's mediology. Situated at the crossroads of philosophy, theology, anthropology, archaeology, history, sociology, political sciences, semiotics, media and cultural studies, mediology is a relatively autonomous discipline that analyses the totality of the processes of mediation that intervene between culture and agency, and transform ideas into a material force. Mediology or mediation studies broadens the notion of media so as to include all material and institutional vectors of communication and defines mediation as the totality of interactions between culture and technology that make the diffusion (through space) and the transmission (over time) of ideas possible.
Between Art and Gameness: Critical Theory and Computer Game Aesthetics
Authors: Kirkpatrick Graeme
Published: April 2007

This article argues that the computer game can be a locus of aesthetic form in contemporary culture. The context for understanding this claim is the decline of the artwork as bearer of form in the late 20th century, as this was understood by Adorno. Form is the enigmatic other of instrumental reason that emerges spontaneously in creative works and, in the modern era, is defined as that which makes them captivating and enigmatic yet resistant to analytic understanding. Clarification of the ways in which form is at work in game play is sought from aesthetic theory (Kant), ludology (or theory of games), and the idea of a neo-baroque entertainment culture (Ndalianis). Kant emphasized the role of play in the constitution of imaginary realms associated with aesthetic pleasure. Ludology takes play as an anthropological given differentiated historically by the development of game structures. Neo-baroque theory postulates a labyrinthine, complex and de-centred entertainment culture, largely shaped by computing as a cultural practice. The article synthesizes insights from these perspectives and, drawing on ideas from Adorno and Benjamin, argues that computer games can occupy an oppositional or critical role within contemporary aesthetics and culture. Reflection on the constitutive processes of computer game play discloses a new place for instrumental reason within aesthetic experience, as the dialectic of form and analysis migrates from traditional art materials to digital electronics.
Cutting the Trees of Knowledge: Social Software, Information Architecture and Their Epistemic Consequences
Authors: Schiltz Michael , Truyen Frederik , Coppens Hans
Published: April 2007

This article inquires whether and to which degree some fundamental traits of the World Wide Web may encourage us to revise traditional conceptions of what constitutes scientific information and knowledge. Turning to arguments for `open access' in scientific publishing and its derivatives (open content, open archives, etc.), contemporary tendencies in `social software' and knowledge sharing, the authors project a new look on knowledge, dissociated with linear notions of cumulation, progression, and hierarchy (e.g. of scientific argument), but related to circularity, heterarchy, and evolution. Arguing from a medium theoretical perspective, they illustrate their ideas with developments in library science, current debates in epistemology and theories about information architecture, with a particular focus on `unsystematic' folksonomies.
Seeking Authenticity: Women and Learning in the Catholic Worker Movement
Authors: Parrish Marilyn McKinley , Taylor Edward W.
Published: April 2007

Oral history interviews form the basis of an investigation into both the context and the everyday actions that contributed to the learning environment for women within the Catholic Worker Movement during the 1930s and 1940s. Findings reveal that narrators (a) were grounded in a variety of learning environments including family, Catholic Church, and school contexts; (b) sought adventure and authenticity as young adults; (c) practiced compassionate and critical-systemic faith within the Catholic Worker, which resulted in a new framework or way of seeing; (d) developed significant relationships that fostered learning in new ways; and (d) despite oppressive narrowing of opportunity for some because of their gender, learned to trust personal conscience as it guided them into positions of leadership that were unusual at the time within their local parishes. This study contributes to the expanding boundaries of the history of adult education by addressing issues of gender, spirituality, and learning in social movements.
Rhizoactivity: Toward a Postmodern Theory of Lifelong Learning
Authors: Dae Joong Kang
Published: April 2007

Although the loss of certainty in the age of postmodernism is questioning knowledge production in general, the emerging discourse of lifelong learning demands a different theory of adult learning in particular. This article aims to offer a conceptual tool for describing learning in adulthood in terms of postmodern and lifelong learning conditions. It approaches the problem from the images of learning and learner that adult education scholarship has produced and identifies that adult learning theory attempts to signify foundational certainty by using binary-trapped adjectives. The author argues that insofar as we continue with the adjective-plus-learning theory, we cannot escape binary thought. The author proposes a new concept, rhizoactivity, to navigate multiplicity of learning in a postmodern world. Anticipated benefits of employing rhizoactivity in understanding learning are discussed in terms of postmodern and lifelong learning conditions.
Histopathological effects of organometallic maneb on testis in rats: a light and electron microscopic study
Authors: Deveci Engin
Published: April 2007

Maneb is a dithiocarbamate fungicide that contains manganese. Dithiocarbamates are considered to be chemicals of low toxicity. An experimental group (n=10) received maneb (obtained from Hoecht-Shering) at a concentration of 250 ppm in distilled water five days a week (treatment time is three weeks). It was orally administered by an orogastric tube. Acute oral LD 50 for male rats has been found to be 6750 mg/kg. The control group (n=10) received distilled water. The whole body and testis weights of male rats were taken, and significant differences in body weight appeared between the control and treated groups (P<0.01). No statistical difference was found in the testis weights between the control and treated groups (P<0.05). Degeneration in spermatic cells can be seen in a few seminiferous tubules and vascularization. Transmission electron microscopy, interstitial cell and blood vessels of maneb-treated rat testis did not show any changes. Leydig cells with their large, excentric nuclei, cytoplasm with granular endoplasmic reticulum and other cell organelles appeared to be normal. Sertoli cells appeared unusually as a well developed rough endoplasmic reticulum and Golgi complexes had irregular compacted chromatin. Changes in Sertoli cell mitochondria included swelling and loss of cristae. Toxicology and Industrial Health 2006; 22: 395-398.
Liver nuclear and microsomal CYP2E1-mediated metabolism of xenobiotics in rats chronically drinking an alcohol-containing liquid diet
Authors: Díaz Gómez María I. , Fanelli Silvia L. , Delgado de Layño Aurora M.A. , Castro José A. , Castro Gerardo D.
Published: April 2007

In previous studies from our laboratory, the presence in highly purified liver nuclei of metabolic pathways for processing ethanol (EtOH), N-nitrosodimethylamine (NDMA), carbon tetrachloride and chloroform was reported. All these chemicals are known to be metabolized in liver microsomes, via cytochrome P450 2E1 (CYP2E1)-mediated processes. In the present work we checked whether rat liver nuclei from rats chronically drinking an alcohol-containing liquid diet exhibited an enhanced ability to metabolize chemicals known to require CYP2E1 participation for given metabolic transformations. The nicotinamide adenosine dinucleotide phosphate (NADPH)-requiring metabolism of p-nitrophenol to p-nitrocathecol; the activation of carbon tetrachloride to trichloromethyl radicals, covalently binding to proteins; and the ring hydroxylation of aniline and o-toluidine were studied. Comparison of the obtained nuclear activities against the one present in the microsomal counterpart, and their respective response to the EtOH inductive effect after repetitive exposure to it, was studied. The obtained results showed that rat liver nuclei exhibited less pnitrophenol hydroxylase activity than microsomes, but it was inducible by repetitive alcohol drinking to equivalent levels of those of microsomes from control animals. Nuclei exhibited the ability to activate CCl4, which was significantly enhanced by alcohol drinking. Aniline was ring hydroxylated in liver microsomes but not in nuclei from either control or EtOH-treated animals. In contrast, nuclei and microsomes metabolized o-toluidine to ring hydroxylated products. They are considered less toxic in nature but other authors reported a genotoxic effect for one of them. The production of the ring hydroxylated metabolites was enhanced by repetitive EtOH drinking. Results suggest that nuclear metabolism of xenobiotics might be relevant for either activations or detoxications mediated by CYP2E1 and that repetitive exposure to EtOH might significantly modulate those processes. Toxicology and Industrial Health 2006; 22: 367-374.
Effect of chronic fluorosis on lipid peroxidation and histology of lung tissues in first and second generation rats
Authors: Oncu Meral , Gulle Kanat , Karaoz Erdal , Gultekin Fatih , Karaoz Sureyya , Karakoyun Inanc , Mumcu Ethem
Published: April 2007

This experiment was designed to investigate the lipid peroxidation and histological effects of chronic fluorosis on first and second generation rat lung tissues.

Sixteen, virgin, female Wistar rats were mated with eight males (2:1) for approximately 12 h to obtain first-generation rats. Pregnant rats were divided into two experimental groups (control and fluoride supplemented). The pregnant rats in the fluoride-supplemented group were exposed to 30 mg/L sodium fluoride (NaF) in commercial drinking water containing 0.07 mg/L NaF throughout the gestation and lactation periods. After the lactation period, young animals (first generation; F1) were exposed to the same amount of NaF in drinking water for four months. At the end of the four-month experimental period, nine randomly-chosen male rats (F1) were sacrificed and lung tissues were removed for histopathological and enzymatic lipid peroxidation examination. The second generation rats were obtained from the remaining rats by the same method. They were also treated similarly. At the end of the four-month experimental period, nine randomly-chosen male rats (F2) were sacrificed, and the lungs were removed for histological and lipid peroxidation examination. The rats in the control groups underwent the same procedure without NaF supplementation.

It was found that the plasma fluoride and the lung TBARS levels of fluoride supplemented F1 and F2 rats were higher than controls. There were marked histological changes in the lung tissues of fluoride supplemented F1 and F2 rats, as follows: in F1 rats; loss of alveolar architecture, emphysematous areas, descuamation of alveolar epithelium and alveolar congestion were observed. There were thickened interalveolar septae and congestion of alveolar septal vessels. Intraparenchymal thick-walled vessels were also observed. There were markedly perivascular and intraparenchymal focal mononuclear cell infiltrations. In F2 rats, in addition to these changes, there were lipid cell hyperplasia and increased connective tissue mass in the parenchymal areas.

It is concluded that chronic fluorosis causes a marked destruction in lung tissues of F1 and F2 rats by causing lipid peroxidation. Toxicology and Industrial Health 2006; 22: 375-380.
ATSDR evaluation of the health effects of zinc and relevance to public health
Authors: Roney Nickolette , Osier Mark , Paikoff Sari J. , Smith Cassandra V. , Williams Malcolm , De Rosa Christopher T.
Published: April 2007

As part of its mandate, the Agency for Toxic Substances and Disease Registry (ATSDR) prepares toxicological profiles on hazardous chemicals found at Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) National Priorities List (NPL) sites, which have the greatest public health impact. These profiles comprehensively summarise toxicological and environmental information. This article constitutes the release of portions of the Toxicological Profile for Zinc. The primary purpose of this article is to provide public health officials, physicians, toxicologists, and other interested individuals and groups with an overall perspective on the toxicology of zinc. It contains descriptions and evaluations of toxicological studies and epidemiological investigations, and provides conclusions, where possible, on the relevance of toxicity and toxicokinetic data to public health. Toxicology and Industrial Health 2006; 22: 423-493.
Clinical manifestations of lead workers of Mangalore, India
Authors: Kuruvilla Ajee , Pillay V.V. , Adhikari Prabha , Venkatesh T. , Chakrapani M. , Jayaprakash Rao H.T. , Bastia Binaya K. , Rajeev A. , Saralaya K.M. , Rai Maneesh
Published: April 2007

Objective: To correlate blood lead levels and clinical manifestations. Participants: Battery workers and painters (occupationally exposed to lead in and around Mangalore, India) and occupationally unexposed controls. Main outcome measures: We measured the blood lead levels by anodic stripping voltammetry, and a clinical examination was carried out on all participants. Results: There was a statistically significant difference between the lead-exposed group and controls with respect to clinical manifestations. The prominent findings among the lead-exposed group were fatigue, abdominal colic, abdominal discomfort, backache, muscular exhaustability, myalgia and paresthesia, at a blood lead level ranging from 0.4 to 116.6 μg/dL. Conclusions: Such a study on battery workers and painters has not been reported in India. Several attempts have been made over the years to relate blood lead levels to adverse health effects. It was not possible to determine a precise blood lead level below which symptoms never occur or a blood lead level at which symptoms are always reported. Toxicology and Industrial Health 2006; 22: 405-413.
Mean changes versus dichotomous definitions of improvement
Authors: Anderson Jennifer J
Published: April 2007

In recent years, when reporting the results of clinical trials for chronic disease, including rheumatologic conditions, use has been made of dichotomous definitions of improvement, but it is to be expected that continuous definitions would offer improved discrimination between treatment groups. Nevertheless, a well-constructed dichotomous outcome (usually a composite) has advantages of clinical sense and specificity and may, under a variety of realistic conditions, have power that closely approximates that of standard continuous outcome measures. This has been seen for established dichotomous outcome definitions for two rheumatologic conditions, rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Simulation studies performed using multivariate normal generated data that approximates actual trial data for each of RA and AS patients demonstrate the relative power of several dichotomous and continuous outcomes in realistic situations for each of RA and AS. Although the continuous outcomes are typically more powerful than the dichotomous ones, there are some situations in which the power of a well-defined dichotomous outcome approaches or even exceeds that of a continuous outcome based on mean change.
Developing international consensus on measures of improvement for patients with myositis
Authors: Lachenbruch Peter A. , Miller Frederick W. , Rider Lisa G.
Published: April 2007

We discuss methods of developing consensus in measuring improvement in myositis. We consider selecting candidate variables, reliability and validity, percentage improvement /worsening rules, rules based on CART and logistic regression. We discuss criteria for determining an acceptable rule that include both numerical measures and physician acceptance.
Assessing disease progression using a composite endpoint
Authors: Weng Kee Wong  , Furst Daniel E. , Clements Philip J. , Streisand Jim B.
Published: April 2007

Scleroderma patients usually have serious medical events in several organ systems and it is desirable to have a composite index that accounts for disease activity in these organ systems. We show how one may use a composite `time to event' analysis for evaluating such patients and more generally for patients suffering from a chronic disease. The composite `time to event' analysis requires a composite endpoint with a Kaplan—Meier type analysis. As an illustration, we use data from a clinical trial for scleroderma patients and present sensitivity analysis where one or more of the organ involvement definition criteria are modified.

In addition, we propose desirability functions to monitor patients' disease improvement when the outcomes are all continuous. This method offers several possible advantages over existing methods for measuring patients' improvement.
The Relationship Between the Social Environment Within Religious Organizations and Intake of Fat Versus Fruits and Vegetables
Authors: Hart Alton , Bowen Deborah J. , Kuniyuki Alan , Hannon Peggy , Campbell Marci K.
Published: April 2007

The authors explored associations of social environment with dietary behavior among participants in the Eating for a Healthy Life study, a randomized, low-fat, high-fruit-and-vegetable dietary intervention trial in religious organizations. Data in this report are from baseline telephone surveys of 1,520 persons that assessed dietary behaviors (Fat- and Fiber-Related Diet Behavior Questionnaire) and social environment (Moos Group Environment Scale). After adjusting for demographic characteristics, higher scores on the Cohesion and Order/Organization subscales were associated with higher fruit/vegetable scores (indicating higher fruit and vegetable consumption). Higher scores on the Cohesion, Leader Support, and Order/Organization subscales were also associated with lower fat scores (indicating lower fat intake). Dietary behaviors within religious organizations may be related to positive perceptions of the social environment. These results support further exploration of the potential influence of religious organizations' social environment on health behaviors and its applicability to dietary change interventions.
Spousal Support and Food-Related Behavior Change in Middle-Aged and Older Adults Living With Type 2 Diabetes
Authors: Beverly Elizabeth A. , Miller Carla K. , Wray Linda A.
Published: April 2007

One of the most challenging diabetes-related behavior changes is adhering to a healthful diet. Drawing on the social cognitive theory and social support literature, this qualitative study explores how spousal support influences dietary changes following a diagnosis of type 2 diabetes in middle-aged and older adults. The purpose of this study was to determine how aspects of the spousal relationship translate into behavior changes, specifically adherence to a healthful diet. Analyses revealed five core themes related to dietary adherence: control over food, dietary competence, commitment to support, spousal communication, and coping with diabetes. The themes can be categorized within two key social cognitive theory constructs: reinforcement and self-efficacy. Implications from the focus group data can inform the development of more effective, targeted nutrition messages and programs to provide specific knowledge and skills.
The Collective Repression of `Pathos' in Organization Studies
Authors: Gagliardi Pasquale
Published: April 2007

This paper analyses, from the perspective of the sociology of knowledge, the specific way in which rationalist utilitarianism has influenced both organizational practices and the experts' way of thinking about organizations from the birth of the discipline until the rise of organizational symbolism in the 1970s. The hegemony of the rationalist paradigm—it is argued—led the scientific community to a sort of collective repression of the expressive dimensions of organizational life. The forms of this repression and the expedients adopted to reduce the cognitive dissonance created by this kind of blindness are explored.
Passion, Knowledge and Motivation: Ontologies of Desire
Authors: Linstead Stephen , Brewis Joanna
Published: April 2007

In this paper we address some neglected ontological issues regarding the ideas of passion and knowledge in the contemporary Western context. We argue that passion as a concept can be understood in two main ways. The prevalent interpretation in organization studies is teleological, that of a powerful, purposive motivation to achieve an end result. The second is an ontological understanding of the nature of desire, which in itself is double-sided. Using the ideas of Foucault and Bataille, we suggest desire can be read as lack but also/alternatively as a free-flowing creative force operating behind the quest for knowledge. Through the power effects of discourses like knowledge management and motivation theory, this flow of desire is curtailed in its ability to make meaning through nonknowledge as well as knowledge. This entails that formless, unpredictable desire is discursively condensed into functional motivation, whilst at the same time the protean, curious urge to connect to the externality of the world becomes structured into the instrumental, conservative management of knowledge. We reflect here on both of these discursive trajectories, as well as on some of their implications.
Senses of Seascapes: Aesthetics and the Passion for Knowledge
Authors: Mack Kathy S.
Published: April 2007

This paper seeks to aesthetically explore the relationship between passion and knowledge. Some of the challenges associated with aesthetic readings surround the location, evocation and representation of multi-sensory experiences and aesthetic expressions. Place-based research indicates that places are important for both aesthetics and meaning. This symbiotic connection between aesthetics and `senses of place' opens an important gangway through which to embark on a journey to locate, evoke and represent the `aesthetic dimension' of seascapes and shipboard life. Conversations with 34 Norwegian seafarers support the relationship between passion and knowledge anchored in seascapes; provide the researcher with a familiar harbour for an impassioned aesthetic reading. Reflections along the voyage consider the importance of an `integrated aesthetic approach' (Brady, 2003) which includes a double focus: on both the aesthetic experiences of organizational members and on the places wherein these experiences are aroused. This aesthetic reading also attends to the `aesthetics' of aesthetic research.
DVDs
Authors: Dean Peter
Published: April 2007

This debate article explores some of the possibilities for the future of the DVD form as a distribution medium for mainstream movies within a UK/USA context. Whilst analogies are being made between the VHS/Betamax format war of the 1980s and the emergence of two rival next-generation DVD formats (Blu-ray and HD-DVD), it is clear that the future of the DVD is now much more complex than the identification of a dominant new and higher-capacity format. The emergence of domestic broadband and authorized movie downloading may challenge the role of the DVD as a distribution medium. At the same time, unauthorized downloading, Web 2.0 and renewed debates around intellectual property rights and legislative jurisdiction are challenging the foundations of film making and distribution. These trends in DVD and online movie consumption suggest, in particular, that DVD add-ons may be a short-lived transitory phenomenon rather than a continuing and integral part of movie consumption in the home.
A DVD Dilemma
Authors: Huang Edgar
Published: April 2007

The Digital Millennium Copyright Act (DMCA) has made ripping Macrovision- or CSSprotected DVDs illegal, but university instructors and students need accessible videos in a digital format for pedagogical purposes. This legal analysis has compared the DMCA with the TEACH Act and the fair use doctrine in the Copyright Act in an attempt to find a viable solution to this dilemma. The study has provided alternative and creative approaches to DVD ripping while finding it necessary to pursue a legal amendment to the DMCA.
Impact of DVD on Translation
Authors: O'Hagan Minako
Published: April 2007

This article discusses the significant influence DVD is having on translation from the perspective of translation studies. Focusing on the language support functionality afforded by this new medium, the author outlines the type of language options commonly provided on DVD film titles of fictional genres and examines the changes introduced by DVDs in relation to translation requirements and new possibilities opening up for translation research. Despite the scant attention paid by media and film studies, the author maintains that the language support functionality afforded by DVD is significant and argues that the approach treating language options as an essential add-on feature of DVD offers a productive research direction in the light of continuing globalization of audiovisual content.
'The DVD of Attractions'?
Authors: Brown Tom
Published: April 2007

/ This essay considers the DVD in relation to Tom Gunning's concept of `the cinema of attractions' (1990 and 2004), identifying parallels in terms of exhibitionism, technological display and the prevalence of direct address. It also stresses textual analysis of DVD menus (something largely neglected in contemporary scholarship) as an important tool for understanding the DVD as a novel `intra-text' (as referred to by Brookey and Westerfelhaus in a 2002 essay). The article focuses on the DVD of The Lion King (dir. Allers and Minkoff, USA, 1994), emphasizing the relationship of the disc and its management of a series of attractions to the Disney theme park. This analysis reveals that, in following a path through The Lion King 's two discs, audiences do not simply view a series of activities and materials `extra' to the film, they circulate and participate in an `enclosed environmental artwork' akin to the Disney theme park.
'The Adventure Continues on DVD'
Authors: Skopal Pavel
Published: April 2007

Research into practices applied by the Hollywood studios on the DVD market requires analysis of the economic logic of the market and the rhetoric of various paratexts accompanying the movies on DVDs, as well as consideration of practices of the television industry. At stake are not only the principles of economy of scope and the strategy of repurposing content that DVD accomplishes, but also the way the studios use DVD like the TV industry uses the internet for an old media's `augmentation', to use John Caldwell's term. Additionally, the extras on DVDs create a frame of reception through their exploitation of institutional practices which are familiar to the viewer from television and home video. The movies on DVD are marketed by the Hollywood cinema in a double mode: the DVD offers theatrical spectacularity as well as the intimacy and `imperfection' of television and home video. DVDs with their high-budgeted franchises provide the best opportunity for combining spectacle, narrative openness and complexity with a sense of intimacy and authenticity.
The Format Wars
Authors: Brookey Robert Alan
Published: April 2007

Soon the DVD format will celebrate its tenth anniversary in the consumer electronics market. In those 10 years, the format has brought about some significant changes in the film industry and the home video market. Given that new DVD formats are entering the market, it might be an opportune moment to reflect on the impact of the DVD and consider its future. This article examines why the DVD format has been successful and the changes it has brought. It then discusses the two formats that may set the standard for the next generation of DVDs, and the challenges this next generation may face in light of new developments in the media market.
Lentiviral vectors containing an enhancer-less ubiquitously acting chromatin opening element (UCOE) provide highly reproducible and stable transgene expression in hematopoietic cells
Authors: Zhang Fang , Thornhill Susannah I. , Howe Steven J. , Ulaganathan Meera , Schambach Axel , Sinclair Joanna , Kinnon Christine , Gaspar H. Bobby , Antoniou Michael , Thrasher Adrian J.
Published: April 2007

Ubiquitously acting chromatin opening elements (UCOEs) consist of methylation-free CpG islands encompassing dual divergently transcribed promoters of housekeeping genes that have been shown to confer resistance to transcriptional silencing and to produce consistent and stable transgene expression in tissue culture systems. To develop improved strategies for hematopoietic cell gene therapy, we have assessed the potential of the novel human HNRPA2B1-CBX3 UCOE (A2UCOE) within the context of a self-inactivating (SIN) lentiviral vector. Unlike viral promoters, the enhancer-less A2UCOE gave rise to populations of cells that expressed a reporter transgene at a highly reproducible level. The efficiency of expression per vector genome was also markedly increased in vivo compared with vectors incorporating either spleen focus-forming virus (SFFV) or cytomegalovirus (CMV) promoters, suggesting a relative resistance to silencing. Furthermore, an A2UCOE-IL2RG vector fully restored the IL-2 signaling pathway within IL2RG-deficient human cells in vitro and successfully rescued the X-linked severe combined immunodeficiency (SCID-X1) phenotype in a mouse model of this disease. These data indicate that the A2UCOE displays highly reliable transcriptional activity within a lentiviral vector, largely overcoming insertion-site position effects and giving rise to therapeutically relevant levels of gene expression. These properties are achieved in the absence of classic enhancer activity and therefore may confer a high safety profile.
Multiple prethymic defects underlie age-related loss of T progenitor competence
Authors: Zediak Valerie P. , Maillard Ivan , Bhandoola Avinash
Published: April 2007

Aging in mice and humans is characterized by declining T-lymphocyte production in the thymus, yet it is unclear whether aging impacts the T-lineage potential of hematopoietic progenitors. Although alterations in the lymphoid progenitor content of aged mouse bone marrow (BM) have been described, irradiation-reconstitution experiments have failed to reveal defects in T-lineage potential of BM hematopoietic progenitors or purified hematopoietic stem cells (HSCs) from aged mice. Here, we assessed T-progenitor potential in unmanipulated recipient mice without conditioning irradiation. T-progenitor potential was reduced in aged BM compared with young BM, and this reduction was apparent at the earliest stages of intrathymic differentiation. Further, enriched populations of aged HSCs or multipotent progenitors (MPPs) gave rise to fewer T-lineage cells than their young counterparts. Whereas the T-precursor frequency within the MPP pool was unchanged, there was a 4-fold decline in T-precursor frequency within the HSC pool. In addition, among the T-competent HSC clones, there were fewer highly proliferative clones in the aged HSC pool than in the young HSC pool. These results identify T-compromised aged HSCs and define the nature and cellular sites of prethymic, age-related defects in T-lineage differentiation potential.
Heterogeneous prognostic impact of derivative chromosome 9 deletions in chronic myelogenous leukemia
Authors: Kreil Sebastian , Pfirrmann Markus , Haferlach Claudia , Waghorn Katherine , Chase Andrew , Hehlmann Rüdiger , Reiter Andreas , Hochhaus Andreas , Cross Nicholas C. P.
Published: April 2007

Derivative chromosome 9 deletions are seen in 10% to 15% of patients with chronic myelogenous leukemia and have been associated with a poor prognosis; however, no studies have been performed in the context of a randomized clinical trial. We developed a DNA-based deletion screen and investigated 339 chronic phase patients treated with interferon-α as first-line therapy in 3 controlled German studies with a median observation time of 7 years. Deletions were detected in pretreatment DNA of 59 of 339 (17%) patients. Of these, 21 spanned the ABL/BCR junction and 38 were centromeric (n = 20) or telomeric (n = 18) of the breakpoint. There was no significant difference in overall survival between deleted and nondeleted patients. Patients with breakpoint-spanning deletions had poorer survival compared with patients without deletions (4.7 versus 7.8 years; P = .003), but this was not significant when censored at allogeneic stem cell transplantation (n = 129) or imatinib (n = 62) treatment in the first chronic phase (P = .078). Unexpectedly, deletions that did not span the breakpoint were associated with improved survival compared with cases without deletions (P = .001). Multiple Cox regression analysis indicated that deletion status (P = .007), age (P = .018), and spleen enlargement (P < .001) were significant independent indicators of survival and confirmed that only deletions spanning the ABL/BCR breakpoint were associated with an adverse prognosis (P = .039).
Physiology of Upward Transport in the Human Female Genital Tract
Authors: ZERVOMANOLAKIS I. , OTT H.W. , HADZIOMEROVIC D. , MATTLE V. , SEEBER B. E. , VIRGOLINI I. , HEUTE D. , KISSLER S. , LEYENDECKER G. , WILDT L.
Published: April 2007

Abstract:  The uterus and fallopian tubes represent a functionally united peristaltic pump under the endocrine control of ipsilateral ovary. We have examined this function by using hysterosalpingoscintigraphy (HSS), recording of intrauterine pressure, electrohysterography, and Doppler sonography of the fallopian tubes. An uptake of labeled particles into the uterus was observed during the follicular and luteal phases of the cycle after application into the vagina. Transport into the oviducts, however, could only be demonstrated during the follicular phase. Furthermore, the predominant transport was into the tube ipsilateral to the ovary containing the dominant follicle. The pregnancy rate following spontaneous intercourse or insemination was higher in those women in whom ipsilateral transport could be demonstrated. The amount of material transported to the ipsilateral tube was increased after oxytocin administration, as demonstrated by radionuclide imaging and by Doppler sonography following instillation of ultrasound contrast medium. An increase in the basal tone and amplitude of contractions was observed after oxytocin administration. These results support the idea that the uterus and fallopian tubes act as a peristaltic pump, which increases transport of sperm into the oviduct ipsilateral to the ovary bearing the dominant follicle. Oxytocin appears to play a critical role in this peristaltic pump. A failure of the peristaltic mechanism is possibly responsible for infertility. We propose the term tubal transport disorder (TTD) as a nosological entity. Results from HSS could be a useful adjunct for choosing treatment modalities in patients with patent fallopian tubes suffering from infertility. These patients may be better served with in vitro fertilization (IVF).
Modalities of Gene Action Predicted by the Classical Evolutionary Biological Theory of Aging
Authors: MARTIN GEORGE M.
Published: April 2007

Abstract:  What might now be referred to as the “classical” evolutionary biological theory of why we age has had a number of serious challenges in recent years. While the theory might therefore have to be modified under certain circumstances, in the author's opinion, it still provides the soundest theoretical basis for thinking about how we age. Nine modalities of gene action that have the potential to modulate processes of aging are reviewed, including the two most widely reviewed and accepted concepts (“antagonistic pleiotropy” and “mutation accumulation”). While several of these nine mechanisms can be regarded as derivatives of the antagonistic pleiotropic concept, they frame more specific questions for future research. Such research should pursue what appears to be the dominant factor in the determination of intraspecific variations in longevity—stochastic mechanisms, most likely based upon epigenetics. This contrasts with the dominant factor in the determination of interspecific variations in longevity—the constitutional genome, most likely based upon variations in regulatory loci.
Molecular Chaperones and the Epigenetics of Longevity and Cancer Resistance
Authors: KRØLL JENS
Published: April 2007

Abstract:  The inherent immortality of embryonic stem cells demonstrates that replicative senescence as possibly the aging of species are epigenetic phenomena. The cellular level of expression of the housekeeping molecular chaperones correlates with longevity and cancer resistance of species. The chaperones are cancer antagonists by acting as genetic buffers, stabilizing the normal phenotype. Probably the progressive age‐related silencing of the housekeeping genes contributes to the phenotype of aging, with the associated increase in cancer incidence. The present review concerns epigenetic chemical, immunological, and hormonal mechanisms, activating chaperone‐ and immune‐response genes, which have proved effective in increasing longevity and cancer resistance. The relation of steroid hormone levels to species longevity, the anticarcinogenic activity of pregnancy hormones, and the influence of hormones on the longevity of social insects, illustrates the importance of hormonal mechanisms for the activation of longevity genes.
Zinc and Inflammatory/Immune Response in Aging
Authors: VASTO SONYA , MOCCHEGIANI EUGENIO , MALAVOLTA MARCO , CUPPARI IRENE , LISTÌ FLORINDA , NUZZO DOMENICO , DITTA VITO , CANDORE GIUSEPPINA , CARUSO CALOGERO
Published: April 2007

Abstract:  Life‐long antigenic burden determines a condition of chronic inflammation, with increased lymphocyte activation and proinflammatory cytokine production. A large number of studies have documented changes in zinc metabolism in experimental animal models of acute and chronic inflammation and in human chronic inflammatory conditions. In particular, modification of zinc plasma concentration, as well as intracellular disturbance of antioxidant intracellular pathways, has been found in aging and in some age‐related diseases. Zinc deficiency is diffused in aged individuals in order to avoid meat and other high zinc content foods due to fear of cholesterol. Rather, they increase the consumption of refined wheat products that lack zinc and other critical nutrients as a consequence of the refining process. On the other hand, plasma zinc concentration is influenced by proinflammatory cytokines (IL‐6 and TNF‐α) and by metallothioneins (MT) homeostasis, which is in turn affected by proinflammatory cytokines. MT increase in aging and chronic inflammation allowing a continuous sequestration of intracellular zinc with subsequent low zinc ion availability against stressor agents and inflammation. This phenomenon leads to an impaired inflammatory/immune response in the elderly. A major target of zinc is NF‐κB, a transcription factor critical for the expression of proinflammatory cytokines whose production is regulated by extra‐ and intracellular activating and inhibiting factors interacting with the regulatory elements on cytokine genes. Effects of zinc on translocation of NF‐κB have been attributed to the suppression of phosphorylation and degradation of the inhibitory proteins (A20) that normally sequester it in the cytoplasm. Moreover, this factor and A20 are regulated by specific genes involved in inflammation and by intracellular zinc ion availability. So, it is not so surprising that zinc deficiency is constantly observed in chronic inflammation, such as in old individuals. On the other hand, cytokine genes are highly polymorphic and some of these polymorphisms are associated with atherosclerosis and diabetes type 2. Therefore, zinc turnover, via MT homeostasis, in individuals genetically predisposed to a dysregulation of the inflammatory/immune response may play a crucial role in causing possible adverse events with the appearance of age‐related diseases.
PECAM‐1/CD31 in Infarction and Longevity
Authors: LISTÌ FLORINDA , CARUSO CALOGERO , BALISTRERI CARMELA RITA , GRIMALDI MARIA PAOLA , CARUSO MARCO , CAIMI GREGORIO , HOFFMANN ENRICO , LIO DOMENICO , CANDORE GIUSEPPINA
Published: April 2007

Abstract:  Inflammation has recently proven to be associated with the pathogenesis of atherosclerosis and inflammatory genes are good candidates for the risk of developing atherosclerosis. The early phase of atherosclerosis involves the recruitment of inflammatory cells from the circulation and their transendothelial migration. This process is mainly mediated by cellular adhesion molecules, which are expressed by the vascular endothelium and by circulating leukocytes in response to several inflammatory stimuli. Adhesion of circulating cells to the arterial surface is among the first detectable events in atherogenesis. Cellular adhesion molecules, expressed by the vascular endothelium and by circulating leukocytes, mediate cell recruitment and their transendothelial migration. Platelet endothelial cellular adhesion molecule‐1 (PECAM‐1/CD31), involved in this migration, has been associated with the developmental course of atherosclerosis. Studies have investigated an association between coronary heart disease (CHD) and single nucleotide polymorphisms (SNP) located in functionally important domains of the PECAM‐1/CD31 gene, with contrasting results. In particular, we previously analyzed for the following PECAM‐1/CD31 SNP: Val125Leu, Asn563Ser, and Gly670Arg. The frequency of the Gly670Arg polymorphism was significantly higher in patients with myocardial infarction (MI), whereas the frequencies of the other two SNP (Leu125Val and Ser563Asn) were not significantly different between patients and controls. To check the validity of our results, we have analyzed the distribution of these SNP in centenarian men (age >99) from our homogeneous Sicilian population, since our previous studies have demonstrated that alleles associated with MI susceptibility are not included in the genetic background favoring longevity. We showed, as regard to polymorphisms of PECAM‐1/CD31, that there were no significant differences between male patients affected by MI, male controls, and male centenarians. According to our hypothesis present results seemingly do not support a role for these SNP in conferring the susceptibility to MI at least in this Italian population.
Plasma Levels of Apolipoprotein E and Risk of Stroke in Old Age
Authors: VAN VLIET PETER , MOOIJAART SIMON P. , DE CRAEN ANTON J. M. , RENSEN PATRICK C. N. , VAN HEEMST DIANA , WESTENDORP RUDI G. J.
Published: April 2007

Abstract:  Recently, high plasma apoE levels have been shown to be related to increased cardiovascular mortality, independent of APOE genotype. Here we studied the association of plasma apoE levels with risk of stroke. Within the Leiden 85‐plus Study, a prospective population‐based study of 561 subjects aged 85 years, we measured plasma apoE level and determined APOE genotype at base line. The presence of stroke in the medical history and the incidence of stroke during a 5‐year follow‐up period were assessed by interviewing treating physicians. At base line, an increase of one standard deviation (SD) of plasma apoE level associated with a 1.47‐fold higher risk of a history of stroke (P= 0.025). During follow‐up, an increase of one SD of plasma apoE level associated with an increased risk of stroke (risk of stroke: 1.58, P= 0.010). This association was also observed in ɛ3ɛ3‐ (1.95, P= 0.002) and ɛ3ɛ4 carriers (3.01, P= 0.008), but not in ɛ2ɛ3 carriers (0.62, P= 0.440). In conclusion, in old age, except for ɛ2‐allele carriers, high plasma apoE levels are associated with a higher risk of stroke, independent of APOE genotype, plasma levels of lipids, and other cardiovascular risk factors.
Plasma Levels of Apolipoprotein E and Cognitive Function in Old Age
Authors: MOOIJAART SIMON P. , VAN VLIET PETER , VAN HEEMST DIANA , RENSEN PATRICK C. N. , BERBÉE JIMMY F. P. , JOLLES JELLE , DE CRAEN ANTON J. M. , WESTENDORP RUDI G. J.
Published: April 2007

Abstract:  The relationship between structural variants of the apolipoprotein E gene, APOEɛ2/ɛ3/ɛ4, and dementia is well established, whereas the relationship of plasma apoE levels with dementia is less clear. Plasma apoE levels are under tight genetic control but vary widely within the various genotypes indicating that the APOEɛ2/ɛ3/ɛ4 locus explains only a small fraction of this variation. Here we studied the association of plasma apolipoprotein E (apoE) levels with cognitive function in the elderly population at large. Within the Leiden 85‐plus Study, a prospective population‐based study of subjects aged 85 years, we measured plasma apoE level and genotype at base line. During a 5‐year follow‐up period, cognitive function was annually assessed using the Mini Mental State Examination (MMSE) and a standardized neuropsychological test battery. Among ɛ3ɛ3 carriers (n= 324), high plasma apoE levels associated with impaired global cognitive function (–1.10 points change in MMSE score per one standard deviation increase of plasma apoE level, P= 0.001), as well as lower attention (P= 0.064), speed and memory function (all P < 0.05). Adjustment for cardiovascular risk factors and exclusion of all subjects who suffered a stroke did not materially change the associations. Similar estimates were obtained in ɛ3ɛ4 carriers (n= 100), but not in ɛ2ɛ3 carriers (n= 90). We conclude that in old age, in non‐ɛ2‐allele carriers, high plasma apoE levels are associated with cognitive impairments, independent of genotype, cardiovascular risk factors, and stroke.
CCR5 Receptor
Authors: BALISTRERI CARMELA RITA , CARUSO CALOGERO , GRIMALDI MARIA PAOLA , LISTÌ FLORINDA , VASTO SONYA , ORLANDO VALENTINA , CAMPAGNA ANNA MARIA , LIO DOMENICO , CANDORE GIUSEPPINA
Published: April 2007

Abstract:  The CC chemokine receptor 5 (CCR5) is a member of CC‐chemokine receptor family. CCR5 has the characteristic structure of a seven transmembrane G protein–coupled receptor (GPCR), which regulates trafficking and effector functions of memory/effector Th1 cells, macrophages, NK cells, and immature dendritic cells. CCR5 and its ligands are important molecules in viral pathogenesis. CCR5 represents the co‐receptor for macrophage (M) and dual (T cell and M)‐tropic immunodeficiency viruses. Recent evidence has also demonstrated the role of CCR5 in a variety of human diseases, ranging from infectious and inflammatory diseases to cancer. In this article, we describe the involvement of CCR5 in two age‐related diseases, atherosclerosis and Alzheimer's disease, suggesting a possible role of chemokine system on these diseases' pathophysiology. Finally, we review the data on the probable association between CCR5Δ32 deletion and cardiovascular diseases and Alzheimer's disease.