bluuebunny/crossref_metadata_2025 huggingface dataset:
Antiviral Effect of Orally Administered (−)-β-d-2-Aminopurine Dioxolane in Woodchucks with Chronic Woodchuck Hepatitis Virus Infection
Authors: Menne Stephan , Asif Ghazia , Narayanasamy Jannan , Butler Scott D. , George Andrea L. , Hurwitz Selwyn J. , Schinazi Raymond F. , Chu Chung K. , Cote Paul J. , Gerin John L. , Tennant Bud C.
Published: July 2007

(−)-β-d-2-Aminopurine dioxolane (APD) is a nucleoside prodrug that is efficiently converted to 9-(β-d-1,3-dioxolan-4-yl)guanine (DXG). DXG has antiviral activity in vitro against hepatitis B virus (HBV) but limited aqueous solubility, making it difficult to administer orally to HBV-infected individuals. APD is more water soluble than DXG and represents a promising prodrug for the delivery of DXG. A placebo-controlled, dose-ranging efficacy and pharmacokinetic study was conducted with woodchucks that were chronically infected with woodchuck hepatitis virus (WHV). APD was efficiently converted to DXG after oral and intravenous administrations of APD, with serum concentrations of DXG being higher following oral administration than following intravenous administration, suggestive of a considerable first-pass intestinal and/or hepatic metabolism. APD administered orally at 1, 3, 10, and 30 mg/kg of body weight per day for 4 weeks produced a dose-dependent antiviral response. Doses of 3 and 10 mg/kg/day reduced serum WHV viremia by 0.4 and 0.7 log10copies/ml, respectively. The 30-mg/kg/day dose resulted in a more pronounced, statistically significant decline in serum WHV viremia of 1.9 log10copies/ml and was associated with a 1.5-fold reduction in hepatic WHV DNA. Individual woodchucks within the highest APD dose group that had declines in serum WHV surface antigen levels, WHV viremia, and hepatic WHV DNA also had reductions in hepatic WHV RNA. There was a prompt recrudescence of WHV viremia following drug withdrawal. Therefore, oral administration of APD for 4 weeks was safe in the woodchuck model of chronic HBV infection, and the effect on serum WHV viremia was dose dependent.
Morphology, Molecular Codes, and Circuitry Produce the Three-Dimensional Complexity of the Cerebellum
Authors: Sillitoe Roy V. , Joyner Alexandra L.
Published: July 2007

The most noticeable morphological feature of the cerebellum is its folded appearance, whereby fissures separate its anterior-posterior extent into lobules. Each lobule is molecularly coded along the medial-lateral axis by parasagittal stripes of gene expression in one cell type, the Purkinje cells (PCs). Additionally, within each lobule distinct combinations of afferents terminate and supply the cerebellum with synchronized sensory and motor information. Strikingly, afferent terminal fields are organized into parasagittal domains, and this pattern bears a close relationship to PC molecular coding. Thus, cerebellum three-dimensional complexity obeys a basic coordinate system that can be broken down into morphology and molecular coding. In this review, we summarize the sequential stages of cerebellum development that produce its laminar structure, foliation, and molecular organization. We also introduce genes that regulate morphology and molecular coding, and discuss the establishment of topographical circuits within the context of the two coordinate systems. Finally, we discuss how abnormal cerebellar organization may result in neurological disorders like autism.
The Tangle of Nuclear Receptors that Controls Xenobiotic Metabolism and Transport: Crosstalk and Consequences
Authors: Pascussi Jean-Marc , Gerbal-Chaloin Sabine , Duret Cédric , Daujat-Chavanieu Martine , Vilarem Marie-José , Maurel Patrick
Published: July 2007

The expression of many genes involved in xenobiotic/drug metabolism and transport is regulated by at least three nuclear receptors or xenosensors: aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR), and pregnane X receptor (PXR). These receptors establish crosstalk with other nuclear receptors or transcription factors controlling signaling pathways that regulate the homeostasis of bile acids, lipids, glucose, inflammation, vitamins, hormones, and others. These crosstalks are expected to modify profoundly our vision of xenobiotic/drug disposition and toxicity. They provide molecular mechanisms to explain how physiopathological stimuli affect xenobiotic/drug disposition, and how xenobiotics/drugs may affect physiological functions and generate toxic responses. In addition, the possibility that xenosensors may control other signaling pathways opens the way to new pharmacological opportunities.
Phosphodiesterase Type 5 Is Highly Expressed in the Hypertrophied Human Right Ventricle, and Acute Inhibition of Phosphodiesterase Type 5 Improves Contractility
Authors: Nagendran Jayan , Archer Stephen L. , Soliman Daniel , Gurtu Vikram , Moudgil Rohit , Haromy Alois , St. Aubin Chantal , Webster Linda , Rebeyka Ivan M. , Ross David B. , Light Peter E. , Dyck Jason R.B. , Michelakis Evangelos D.
Published: July 2007

Background—

Sildenafil was recently approved for the treatment of pulmonary arterial hypertension. The beneficial effects of phosphodiesterase type 5 (PDE5) inhibitors in pulmonary arterial hypertension are thought to result from relatively selective vasodilatory and antiproliferative effects on the pulmonary vasculature and, on the basis of early data showing lack of significant PDE5 expression in the normal heart, are thought to spare the myocardium.

Methods and Results—

We studied surgical specimens from 9 patients and show here for the first time that although PDE5 is not expressed in the myocardium of the normal human right ventricle (RV), mRNA and protein are markedly upregulated in hypertrophied RV (RVH) myocardium. PDE5 also is upregulated in rat RVH. PDE5 inhibition (with either MY-5445 or sildenafil) significantly increases contractility, measured in the perfused heart (modified Langendorff preparation) and isolated cardiomyocytes, in RVH but not normal RV. PDE5 inhibition leads to increases in both cGMP and cAMP in RVH but not normal RV. Protein kinase G activity is suppressed in RVH, explaining why the PDE5 inhibitor–induced increase in cGMP does not lead to inhibition of contractility. Rather, it leads to inhibition of the cGMP-sensitive PDE3, explaining the increase in cAMP and contractility. This is further supported by our findings that, in RVH protein kinase A, inhibition completely inhibits PDE5-induced inotropy, whereas protein kinase G inhibition does not.

Conclusions—

The ability of PDE5 inhibitors to increase RV inotropy and to decrease RV afterload without significantly affecting systemic hemodynamics makes them ideal for the treatment of diseases affecting the RV, including pulmonary arterial hypertension.
Aging Process on Spectrally Determined Spontaneous Baroreflex Sensitivity
Authors: Fauvel Jean-Pierre , Cerutti Catherine , Mpio Ignace , Ducher Michel
Published: July 2007

The interindividual age-related decrease in baroreflex sensitivity (BRS) was reported in many cross-sectional studies. However, the long-term intraindividual decrease in BRS has never been confirmed by longitudinal studies. Data obtained from a 5-year prospective study designed to assess the 5-year stress effects on blood pressure (BP) provided the opportunity to assess longitudinal aging process on spectrally determined BRS (S-BRS) using the cross spectral analysis. This analysis was carried out in 205 men aged between 18 and 50 years who had 2 valid beat to beat BP recordings (Finapress) at a mean 5-year interval. At inclusion and at end of follow-up, S-BRS was significantly correlated with age (
r
=−0.50,
P
<0.001,
r
=−0.33,
P
<0.001 respectively). Interestingly, the slopes and the intercepts were not significantly different at a 5-year interval. This result is in favor of the good reproducibility of S-BRS. The attenuation with age of S-BRS was calculated at 3.6% a year. This decrease was slightly higher than the one obtained with the baseline data (2.3% per year). This longitudinal study provided, for the first time, an estimate of the slope of the age-related physiological S-BRS decrease in a mid-aged healthy male population. Our findings reinforce the interest of evaluating spontaneous BRS reported to predict hypertension and cardiovascular events in various populations.
Residual Strength of Damaged Glass/Epoxy Tubular Structures
Authors: Tarfaoui M. , Gning P.B. , Collombet F.
Published: July 2007

This article presents results from static and dynamic tests on thick filament wound glass/epoxy tubes. The first part involves the identification of damage initiation and its development. Ultrasonic inspection was employed first to determine projected damage areas. A large number of samples were then sectioned and polished and the true damage area was revealed by a dye penetrant technique. This has made possible detailed descriptions of damage development. The true damage area is roughly 10 times the projected area. The second part of the article is concerned with the evaluation of the influence of this damage on residual strength under hydrostatic pressure loading. The improved understanding of these phenomena and the development of predictive tools is part of an ongoing effort to improve the long-term integrity of composite structures for underwater applications.
Determination of Calibration Factors of the Hole Drilling Method for Orthotropic Composites using an Exact Solution
Authors: Shokrieh Mahmood M. , Ghasemi K. Ahmad R.
Published: July 2007

The hole drilling method has been used for measurement of the residual stresses in various materials. The released strains measured by the hole drilling method are converted to residual stresses using calibration factors. There is a standard for the hole drilling method for isotropic materials. Also for orthotropic materials, there are various methods for converting the released strains to residual stresses. In these methods the numbers of calibration factors vary from two to nine (a three by three matrix). In this article, calibration factors of the orthotropic plates are determined based on an exact solution method. For this purpose, assuming a plane stress condition, stresses and strains around the area under a rosette strain gage mounted to an orthotropic plate are calculated. A hole in the center of the rosette strain gage changes the distribution of the stresses and strains. Using the closed form solution proposed in this research the released strains and the calibration factors are calculated, and the residual stresses are found. Also, calibration factors for any orthotropic material with any level of orthotropy are calculated. These factors are independent of the loading and depend on the material properties of orthotropic materials and the ratio of the rosette diameter to the hole diameter. The material properties and the ratio of the rosette diameter to the hole diameter are considered in the equations, therefore there is no need for presenting the results in tabular form or any interpolations. The results for an orthotropic unidirectional ply made of carbon/epoxy are presented. Also, the calibration factors for three different unidirectional composites are calculated. The results obtained from the proposed closed form solution are compared with the simulated hole drilling method. A good agreement between the results shows the reliability of the closed form solution presented in this study.
Prevalence of hyperprolactinaemia in a naturalistic cohort of schizophrenia and bipolar outpatients during treatment with typical and atypical antipsychotics
Authors: Bushe Chris , Shaw Michael
Published: July 2007

Hyperprolactinaemia is a common finding in patients treated with antipsychotics. A complete cohort of 194 schizophrenia and bipolar disorder patients receiving antipsychotics in a single community mental health trust in Halifax UK underwent routine prolactin screening in the absence of any reLevant symptomatoLogy. Values above the upper limit of normal were measured in 38% of the cohort and were more common in females (52%) than males (26%). Significantly elevated levels (>1000 mIU/l) were measured in 21% of the cohort. Risperidone monotherapy treatment was associated with hyperprolactinaemia in 69% of patients ( n = 35) and in 100% of female patients ( n = 16) and amisulpride monotherapy in 100% ( n = 7). Prolactin screening is not currently undertaken routinely in the UK. These data give some indication of prevalence of varying degrees of hyperproLactinaemia that might be found when screening an asymptomatic cohort of schizophrenia and bipolar outpatients. Clinicians may be helped by the reporting of such categorical data from clinical trials in addition to mean cohort values of prolactin. Long-term hyperprolactinaemia may be associated with clinical sequeLae in some patients.
Synthesis of Polyimides from 3,3'-dihydroxybenzidine and Conversion to Polybenzoxazoles
Authors: Okabe Takahiro , Morikawa Atsushi
Published: July 2007

The polyimides containing the hydroxy group were synthesized from 3,3 '-dihydroxybenzidine (I) and previously prepared tetracarboxylic dianhydrides, 3,3''',4,4'''- p-quaterphenyltetracarboxylic dianhydride (IId), 3,3'''',4,4''''- p-quinquephenyltetracarboxylic dianhydride (IIe) and 3,3''''',4,4'''''- p-sexiphenyltetracarboxylic dianhydride (IIf), and the properties were compared with those of corresponding polyimides from commercially available dianhydrides. The polyimides were synthesized by the conventional two-step procedure of ring-opening polyaddition in N-methyl-2-pyrrolidinone (NMP) and subsequent thermal cyclic dehydration. All the polyimides were soluble in NMP on heating. The glass transition temperature ( Tg) of the polyimides ranged from 336—360°C, and were not dependent on the structure of tetracarboxylic dianhydride. The storage modulus of some polyimides did not decrease at high temperature. All the polyimides underwent thermal conversion to polybenzoxazoles upon heating to 500°C for 1 h under vacuum. The thermal conversion of the polyimides to polybenzoxazoles was confirmed by Fourier transform infrared spectrometry. The 10% weight loss temperature ( T10) of the polybenzoxazoles was 530—700°C in nitrogen, and the polybenzoxazoles were thermally stable. In particular, the T10 values of the polybenzoxazoles from IId, IIe, and IIf were above 630°C.
Men's Talk
Authors: Clayton Ben , Humberstone Barbara
Published: July 2007

Building on previous discourse analytic studies in the context of male athletic cultures and subcultures, this article uses pro-feminist perspectives to analyse the talk of male university football (soccer) players in the UK. The (re)production of hegemonic masculinity in men's football has largely been taken for granted in sociology of sport, with very little literature producing actual empirical research to support the claim. The study presents extracts of players' conversations from the changing room and student bar, and examines the ways in which the men negotiate masculine positional identity and (re)affirm separation from the `other', such as women and gay men. The three most predominant topics of conversation (excluding omnipresent talk about football itself) were identified as academic studies, alcohol consumption, and women. Each extract of the men's talk was subjected to critical discourse analysis and is discussed in this article in relation to (pro)feminist debates about hegemony and constructions of masculine self.
Sport and Belonging
Authors: Walseth Kristin
Published: July 2007

Even though it is a common understanding among policymakers that playing sport creates feelings of belonging to a community, there is little research that confirms this assumption. The present article focuses on the relationship between sport and belonging. The study is based on life history interviews with 21 young Norwegian Muslim women with immigrant backgrounds, aged between 16 and 25 years. The article suggests that there are different forms of belonging produced through sport. The analysis separates between traditional sport communities that produce social support and more expressivity based sport communities that contribute to identity confirmation and self-image building. Moreover, the article points to the finding that young Muslim women experience a sense of belonging within sports because playing sports is sometimes perceived as a `place of refuge'.
Diversity and the NCLEX-RN: A Double-Loop Approach
Authors: Sitzman Kathleen L.
Published: July 2007

The United States is increasingly ethnically diverse. To provide culturally congruent care to this changing population, nursing programs must attract and support ethnically diverse students through to successful completion of the National Council Licensure Examination for Registered Nurses. Critically examining the literature on this topic revealed three themes: need for a diverse nursing workforce, lack of formal evidence, and narratives of concern. A double-loop theoretical approach that encompasses interventions in elementary and secondary schools, traditional student support services, faculty development initiatives focused on cultural competence, formative and summative evaluations, quantitative and qualitative research, and evidence-based interventions is proposed to address this multifaceted concern.
Faces/Off: Challenges to Postcolonial Theory Along the Hong Kong-Hollywood Axis
Authors: Kohn Nathaniel , Lee Y.S.
Published: July 2007

This article confronts key postcolonial theoretical concepts through an examination of critical incongruities in and between Hollywood and Hong Kong filmic discourses. By challenging certain assumptions of postcoloniality (hybridity, bricolage, the subaltern, etc.), the authors expose inconsistencies in industrial, academic, and literary practices- ambiguities lurking between discursive patterns of Eastern and Western film production, consumption, and criticism—and show how such postcolonial constructs are found wanting when it comes to representing the flux and mangle found in Hollywood/Hong Kong interaction.
Four Stories
Authors: Stone Dan N.
Published: July 2007

Two of these stories explore contemporary work ("The Meeting" and "The Transformation"); two explore contemporary media. The introductions include the author's perceptions of their meaning.
Pierre Bourdieu, Religion, and Cultural Production
Authors: Dillon Michele
Published: July 2007

Recent years have seen increased emphasis on the autonomy of human agency in creating meaning in everyday life. The institutional bias in sociology, however, and its concomitant emphasis on social reproduction rather than change favors hierarchical approaches to cultural production. This is apparent in the theorizing even of sociologists such as Pierre Bourdieu who emphasize the cultural dynamism of religion and other meaning systems. This article critiques the mechanistic underpinnings of Bourdieu’s perspective on religious production and his categorical differentiation between religious producers and consumers. Using data gathered from American Catholics, the author shows that interpretive autonomy allows them to recast the official discourse of the church hierarchy in ways that advance alternative interpretations. Interpretive autonomy is grounded in the Catholic tradition or habitus and is reflexively used by Catholics both to maintain the vibrancy of the church and expand the possibilities for institutional change.
Fragments of Death: Configurations of My Mother
Authors: Rodriguez Dalia
Published: July 2007

This article is a story about the author’s experiences dealing with her mother who had manic depression for a large part of her life. In the story, the author attempts to have the reader understand the difficulties of dealing with a mentally ill parent; the feelings of guilt, frustration, and fear; as well as the deep sense of loss after her death.
Building the Clinton Legacy Through Frame Alignment
Authors: Coles Roberta L.
Published: July 2007

This article examines Clinton’s rhetorical strategy for creating a legacy in light of the imminent end of his second and final term as president. By examining Clinton’s public discourse from 1997 to 1999, with special attention to the period from September 1998 to June 1999, this article argues that Clinton used the frame of his race initiative to centripetally incorporate varied events and policies to redefine and bolster his legacy in the aftermath of scandal and political polarity. Specifically, President Clinton, with an eye on the legacy of the president and the identity of the Democratic Party, gathered the war in Kosovo and the shootings in Littleton, Colorado, along with their attendant disparate policies into one rhetorical frame, thereby supplying a conception of what Clinton’s 6 years as president had been about, a vision and mission for America, and an identity for the Democratic party distinct from the Republicans.
Apprehending Criminals: Genre and Interpretation in Seven
Authors: Gill Pat
Published: July 2007

The film Seven self-consciously explores two methods of discovering and analyzing clues and evidence. These methods work within the film to set up opposing worldviews and work outside the narrative to implicate viewers in the film's interpretive strategies. Seven relies on viewers to situate it in a generic category and plays with its generic status in ways that expand on and undercut viewer expectations. The play with interpretation touches on issues of moral apprehension, personal conviction, and social responsibility. This article examines the anguished pairing of these warring perspectives on a world defined by crime, self-interest, and moral indifference. Seven evinces a longing for a perhaps mythical past in which deep knowledge and thorough analysis of events were privileged over the pragmatic moral shorthand of contemporary modern culture. As it investigates the principal traits of the three protagonists—the spirited convictions of David Mills, the comprehensive despair of William Somerset, and the moral compunction of John Doe—Seven exposes their frightening kinship, demonstrating moral indignation to be a personal obligation and a psychological liability while playing out the ominous pun on criminal apprehension.
"I Am a Man": The Queer Politics of Race
Authors: Pinar William F.
Published: July 2007

In this study of the gender of racial politics and violence in the United States, the author identifies a mangled and repressed homoeroticism lacing White men's hatred of Blacks. He has chosen lynching and prison rape to make explicit the homoeroticism that laces race relations and structures to the gender of racial politics and violence in this country. Despite the radical discontinuities between various historical periods from the antebellum and post-Reconstruction South to post-1960s urban prisons, there are certain nightmarish continuities or historical "throughlines" in American racial politics and violence, throughlines that express the historical and structural crisis of masculinity in the United States.
American Revolution: From the Electoral Gap to the Banana Republic
Authors: Magubane Zine , Ignacio Emily Noelle
Published: July 2007

Through an analysis of the rhetorical strategies used by mainstream U.S. media between November 8, 2000, and March 3, 2001, the authors show how the U.S. mainstream media helped to restabilize the United States as the pillar of democracy and how an analysis of media accounts can expose the "changing nature of the order of things." The authors demonstrate how the image of the United States as the pillar of democracy was protected through an analysis of (a) images of the Third World that provided a vocabulary for describing America's domestic crisis, (b) media descriptions of our own political foibles and descriptions of similar happenings in other countries, and (c) the downplaying of other countries' media accounts of the U.S. 2000 election crisis.
On the Failure of Habermas's Hermeneutic Objectivism
Authors: Kim Kyung-Man
Published: July 2007

In this article, the author first argues that Habermas's distinction between the two modes of language use that, he alleges, are central to the two starkly different modes of human cognitive activities, that is, analytical-empirical sciences and hermeneutics, is untenable and should be eventually abandoned. For, contrary to Habermas's argument, the analytical-empirical sciences, if they are to be properly understood, must also be conceptualized as involving the performative mode of language use that Habermas thinks is characteristic of hermeneutics only. Second, by using historical examples, the author proceeds to demonstrate why Habermas's hermeneutic objectivism that is based on the methodology of rational reconstruction is doomed to remain wedded to the epistemological foundationalism that he wants to displace by introducing his methodology of rational reconstruction.
Reflexive/Diffractive Ethnography
Authors: Schneider Joseph
Published: July 2007

This article calls attention to the productive intersection of various postcriticisms of knowledge production and the critique of ethnography as a writing technology for producing scientific knowledge about others. In particular, poststructural and deconstructive criticism, cultural studies, feminist science studies, postcolonial theory, and queer theory are seen to have focused disruptive and useful attention on the ethnographic I/eye, both inside and outside the professional academic texts of human science. A radical or full reflexivity is seen to be particularly useful in this attention to the one who sees, knows, and writes, but this reflexivity has been criticized by feminist technoscience critic Donna Haraway for being in fact too timid. A consideration of Haraway's preferred strategy based on the metaphor of diffraction, which seeks to effect difference patterns in the local worlds where ethnography is done, closes the article.
Meditations on Manufactured Consent and Historical Agency
Authors: Bradley Richard
Published: July 2007

The article is a study of historical agency and the issues surrounding the Downing Street memo. It compares the understanding of historical agency held by Bush administration officials with the concept as understood by professional historians. It also discusses historical parallels between the Iraq War and the Vietnam War.
Lying in Politics
Authors: Kellner Douglas
Published: July 2007

In this article, the author places the Downing Street Memo in the context of the Bush administration propensity for pursuing a politics of lying. In the past, conservatives traditionally defended values of truth and integrity while attacking dishonesty and lying. During the Clinton administration, conservative defenders of the value of truth like William Bennett constantly attacked Bill Clinton for lying and dishonesty. Yet few, if any, conservatives have spoken up to criticize the Bush administration for its systematic policy of deception and lying. Interrogating the politics of lying, the author analyzes "Bushspeak" in terms of Big, Bold, and Brazen Lies-concepts illustrated with Bush administration discourse on Iraq.
Genetic diversity among major endemic strains of Leptospira interrogans in China
Authors: He Ping , Sheng Yue-Ying , Shi Yao-Zhou , Jiang Xiu-Gao , Qin Jin-Hong , Zhang Zhi-Ming , Zhao Guo-Ping , Guo Xiao-Kui
Published: July 2007

Background

Leptospirosis is a world-widely distributed zoonosis. Humans become infected via exposure to pathogenic Leptospira spp. from contaminated water or soil. The availability of genomic sequences of Leptospira interrogans serovar Lai and serovar Copenhageni opened up opportunities to identify genetic diversity among different pathogenic strains of L. interrogans representing various kinds of serotypes (serogroups and serovars).

Results

Comparative genomic hybridization (CGH) analysis was used to compare the gene content of L. interrogans serovar Lai strain Lai with that of other 10 L. interrogans strains prevailed in China and one identified from Brazil using a microarray spotted with 3,528 protein coding sequences (CDSs) of strain Lai. The cutoff ratio of sample/reference (S/R) hybridization for detecting the absence of genes from one tested strain was set by comparing the ratio of S/R hybridization and the in silico sequence similarities of strain Lai and serovar Copenhageni strain Fiocruz L1-130. Among the 11 strains tested, 275 CDSs were found absent from at least one strain. The common backbone of the L. interrogans genome was estimated to contain about 2,917 CDSs. The genes encoding fundamental cellular functions such as translation, energy production and conversion were conserved. While strain-specific genes include those that encode proteins related to either cell surface structures or carbohydrate transport and metabolism. We also found two genomic islands (GIs) in strain Lai containing genes divergently absent in other strains. Because genes encoding proteins with potential pathogenic functions are located within GIs, these elements might contribute to the variations in disease manifestation. Differences in genes involved in O-antigen biosynthesis were also identified for strains belonging to different serogroups, which offers an opportunity for future development of genomic typing tools for serological classification.

Conclusion

CGH analyses for pathogenic leptospiral strains prevailed in China against the L. interrogans serovar Lai strain Lai CDS-spotted microarrays revealed 2,917 common backbone CDSs and strain specific genes encoding proteins mainly related to cell surface structures and carbohydrated transport/metabolism. Of the 275 CDSs considered absent from at least one of the L. interrogans strains tested, most of them were clustered in the rfb gene cluster and two putative genomic islands (GI A and B) in strain Lai. The strain-specific genes detected via this work will provide a knowledge base for further investigating the pathogenesis of L interrogans and/or for the development of effective vaccines and/or diagnostic tools.
A novel technique for measuring variations in DNA copy-number: competitive genomic polymerase chain reaction
Authors: Iwao-Koizumi Kyoko , Maekawa Kazunori , Nakamura Yohko , Saito Sakae , Kawamoto Shoko , Nakagawara Akira , Kato Kikuya
Published: July 2007

Background

Changes in genomic copy number occur in many human diseases including cancer. Characterization of these changes is important for both basic understanding and diagnosis of these diseases. Microarrays have recently become the standard technique and are commercially available. However, it is useful to have an affordable technique to complement them.

Results

We describe a novel polymerase chain reaction (PCR)-based technique, termed competitive genomic PCR (CGP). The main characteristic of CGP is that different adaptors are added to the sample and control genomic DNAs after appropriate restriction enzyme digestion. These adaptor-supplemented DNAs are subjected to competitive PCR using an adaptor-primer and a locus-specific primer. The amplified products are then separated according to size differences between the adaptors. CGP eliminates the tedious steps inherent in quantitative PCR and achieves moderate throughput. Assays with different X chromosome numbers showed that it can provide accurate quantification. High-resolution analysis of neuroblastoma cell lines around the MYCN locus revealed novel junctions for amplification, which were not detected by a commercial array.

Conclusion

CGP is a moderate throughput technique for analyzing changes in genomic copy numbers. Because CGP can measure any genomic locus using PCR primers, it is especially useful for detailed analysis of a genomic region of interest.
Discovering multiple transcripts of human hepatocytes using massively parallel signature sequencing (MPSS)
Authors: Huang Jian , Hao Pei , Zhang Yun-Li , Deng Fu-Xing , Deng Qing , Hong Yi , Wang Xiao-Wo , Wang Yun , Li Ting-Ting , Zhang Xue-Gong , Li Yi-Xue , Yang Peng-Yuan , Wang Hong-Yang , Han Ze-Guang
Published: July 2007

Background

The liver is the largest human internal organ – it is composed of multiple cell types and plays a vital role in fulfilling the body's metabolic needs and maintaining homeostasis. Of these cell types the hepatocytes, which account for three-quarters of the liver's volume, perform its main functions. To discover the molecular basis of hepatocyte function, we employed Massively Parallel Signature Sequencing (MPSS) to determine the transcriptomic profile of adult human hepatocytes obtained by laser capture microdissection (LCM).

Results

10,279 UniGene clusters, representing 7,475 known genes, were detected in human hepatocytes. In addition, 1,819 unique MPSS signatures matching the antisense strand of 1,605 non-redundant UniGene clusters (such as APOC1, APOC2, APOB and APOH) were highly expressed in hepatocytes.

Conclusion

Apart from a large number of protein-coding genes, some of the antisense transcripts expressed in hepatocytes could play important roles in transcriptional interference via a cis-/trans-regulation mechanism. Our result provided a comprehensively transcriptomic atlas of human hepatocytes using MPSS technique, which could be served as an available resource for an in-depth understanding of human liver biology and diseases.
Dominant inhibition of Fas ligand-mediated apoptosis due to a heterozygous mutation associated with autoimmune lymphoproliferative syndrome (ALPS) Type Ib
Authors: Bi Lilia L , Pan George , Atkinson T Prescott , Zheng Lixin , Dale Janet K , Makris Christopher , Reddy Vishnu , McDonald Jay M , Siegel Richard M , Puck Jennifer M , Lenardo Michael J , Straus Stephen E
Published: July 2007

Background:

Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of lymphocyte homeostasis and immunological tolerance due primarily to genetic defects in Fas (CD95/APO-1;TNFRSF6), a cell surface receptor that regulates apoptosis and its signaling apparatus.

Methods:

Fas ligand gene mutations from ALPS patients were identified through cDNA and genomic DNA sequencing. Molecular and biochemical assessment of these mutant Fas ligand proteins were carried out by expressing the mutant FasL cDNA in mammalian cells and analysis its effects on Fas-mediated programmed cell death.

Results:

We found an ALPS patient that harbored a heterozygous A530G mutation in the FasL gene that replaced Arg with Gly at position 156 in the protein's extracellular Fas-binding region. This produced a dominant-interfering FasL protein that bound to the wild-type FasL protein and prevented it from effectively inducing apoptosis.

Conclusion:

Our data explain how a naturally occurring heterozygous human FasL mutation can dominantly interfere with normal FasL apoptotic function and lead to an ALPS phenotype, designated Type Ib.
Genetic variability in CYP3A4 and CYP3A5in primary liver, gastric and colorectal cancer patients
Authors: Gervasini Guillermo , García-Martín Elena , Ladero José M , Pizarro Rosa , Sastre Javier , Martínez Carmen , García Monserrat , Diaz-Rubio Manuel , Agúndez José AG
Published: July 2007

Background

Drug-metabolizing enzymes play a role in chemical carcinogenesis through enzymatic activation of procarcinogens to biologically reactive metabolites. The role of gene polymorphisms of several cytochrome P450 enzymes in digestive cancer risk has been extensively investigated. However, the drug-metabolizing enzymes with the broader substrate specificity, CYP3A4 and CYP3A5, have not been analyzed so far. This study aims to examine associations between common CYP3A4 and CYP3A5 polymorphisms and digestive cancer risk.

Methods

CYP3A4 and CYP3A5 genotypes were determined in 574 individuals including 178 patients with primary liver cancer, 82 patients with gastric cancer, 151 patients with colorectal cancer, and 163 healthy individuals.

Results

The variant allele frequencies for patients with liver cancer, gastric cancer, colorectal cancer and healthy controls, respectively, were: CYP3A4*1B, 4.8 % (95% C.I. 2.6–7.0), 3.7 % (0.8–6.6) 4.3% (2.0–6.6) and 4.3% (2.1–6.5); CYP3A5*3, 91.8 % (93.0–97.4), 95.7% (92.6–98.8), 91.7% (88.6–94.8) and 90.8% (87.7–93.9). The association between CYP3A4*1B and CYP3A5*3 variant alleles did not significantly differ among patients and controls. No differences in genotypes, allele frequencies, or association between variant alleles were observed with regard to gender, age at diagnosis, tumour site or stage.

Conclusion

Common polymorphisms on CYP3A4 and CYP3A5 genes do not modify the risk of developing digestive cancers in Western Europe.
Relationship of literacy and heart failure in adults with diabetes
Authors: Laramee Ann S , Morris Nancy , Littenberg Benjamin
Published: July 2007

Background

Although reading ability may impact educational strategies and management of heart failure (HF), the prevalence of limited literacy in patients with HF is unknown.

Methods

Subjects were drawn from the Vermont Diabetes Information System Field Survey, a cross-sectional study of adults with diabetes in primary care. Participants' self-reported characteristics were subjected to logistic regression to estimate the association of heart failure and literacy while controlling for social and economic factors. The Short Test of Functional Health Literacy was used to measure literacy.

Results

Of 172 subjects with HF and diabetes, 27% had limited literacy compared to 15% of 826 subjects without HF (OR 2.05; 95% CI 1.39, 3.02; P < 0.001). Adjusting for age, sex, race, income, marital status and health insurance, HF continued to be significantly associated with limited literacy (OR 1.55, 95% CI 1.00, 2.41, P = .05).

After adjusting for education, however, HF was no longer independently associated with literacy (OR 1.31; 95% CI 0.82 – 2.08; P = 0.26).

Conclusion

Over one quarter of diabetic adults with HF have limited literacy. Although this association is no longer statistically significant when adjusted for education, clinicians should be aware that many of their patients have important limitations in dealing with written materials.
Nevoid melanoma of the vagina: report of one case diagnosed on thin layer cytological preparations
Authors: Fulciniti Franco , Ascierto Paolo Antonio , Simeone Ester , Bove Patrizia , Losito Simona , Russo Serena , Gallo Maria Stella , Greggi Stefano
Published: July 2007

Background

Primary melanoma of the vagina is an extremely rare neoplasm with approximately 250 reported cases in the world literature [1–4]. In its amelanotic variant this lesion may raise several differential diagnostic problems in cytological specimens [5]. In this setting, the usage of thin layer cytopathological techniques (Liquid Based Preparations = LBP) may enhance the diagnostic sensitivity by permitting immunocytochemical study without having to repeat the sampling procedure.

The aim of this paper is to describe the cytomorphological presentation of primary vaginal melanoma on LBP since it has not previously been reported up to now, to our knowledge.

Case presentation

a 79-y-o female complaining of vulvar itching and yellowish vaginal discharge underwent a complete gynaecological evaluation during which a LBP cytological sample was taken from a suspicious whitish mass protruding into the vaginal lumen. A cytopathological diagnosis of amelanotic melanoma was rendered. The mass was radically excised and the patient was treated with α-Interferon.

Conclusion

amelanotic melanoma may be successfully diagnosed on LBP cytological preparations. Thin layer preparations may enhance the diagnostic cytomorphological clues to its diagnosis and may permit an adequate immunocytochemical characterization of the neoplasm.
Information transfer: what do decision makers want and need from researchers?
Authors: Dobbins Maureen , Rosenbaum Peter , Plews Nancy , Law Mary , Fysh Adam
Published: July 2007

Purpose

The purpose of this study was to undertake a systematic assessment of the need for research-based information by decision-makers working in community-based organizations. It is part of a more comprehensive knowledge transfer and exchange strategy that seeks to understand both the content required and the format/methods by which such information should be presented.

Methods

This was a cross-sectional telephone survey. Questions covered current practices, research use, and demographic information, as well as preferences for receiving research information. Three types of organizations participated: Children's Treatment Centres of Ontario (CTCs); Ontario Community Care Access Centres (CCACs); and District Health Councils (DHCs). The analysis used descriptive statistics and analyses of variance (ANOVA) to describe and explore variations across organizations.

Results

The participation rate was 70%. The highest perception of barriers to the use of research information was reported by the CCAC respondents, followed by CTCs and DHCs. The CTCs and DHCs reported greater use of research evidence in planning decisions as compared to the CCACs. Four sources of information transfer were consistently identified. These were websites, health-related research journals, electronic mail, and conferences and workshops. Preferred formats for receiving information were executive summaries, abstracts, and original articles.

Conclusion

There were a number of similarities across organization type with respect to perceived barriers to research transfer, as well as the types of activities the organizations engaged in to promote research use in decision-making. These findings support the importance of developing interactive, collaborative knowledge transfer strategies, as well as the need to foster relationships with health care decision-makers, practitioners and policymakers.
Lateral motor column axons execute a ternary trajectory choice between limb and body tissues
Authors: Luria Victor , Laufer Ed
Published: July 2007

Background

Neuronal topographic map formation requires appropriate selection of axonal trajectories at intermediate choice points prior to target innervation. Axons of neurons in the spinal cord lateral motor column (LMC), as defined by a transcription factor code, are thought to innervate limb target tissues exclusively. Axons of the medial and lateral LMC divisions appear to execute a binary decision at the base of the limb as they choose between ventral and dorsal limb trajectories. The cellular logic that guides motor axon trajectory choices into non-limb tissues such as the ventral flank remains unclear.

Results

We determined the spinal cord motor column origin of motor nerves that innervate ventral flank tissues at hindlimb level. We found unexpectedly that a subset of medial LMC axons innervates ventral non-limb mesenchyme at hindlimb level, rather than entering ventral limb mesenchyme. We also found that in a conditional BmprIa mutant where all ventral hindlimb mesenchyme is converted to a dorsal identity, all medial LMC axons are redirected into the ventral flank, while lateral LMC axons innervate the bidorsal limb.

Conclusion

We have found that medial LMC neurons innervate both ventral flank and limb targets. While normally only a subset of medial LMC axons innervate the flank, all are capable of doing so. Furthermore, LMC axons execute a ternary, rather than binary, choice at the base of the limb between ventral flank, ventral limb and dorsal limb trajectories. When making this choice, medial and lateral LMC axons exhibit different and asymmetric relative preferences for these three trajectories. These data redefine the LMC as a motor column that innervates both limb and body tissues.
Femoral vein thrombophlebitis and septic pulmonary embolism due to a mixed anaerobic infection including Solobacterium moorei: a case report
Authors: Martin Claire A , Wijesurendra Rohan S , Borland Colin DR , Karas Johannis A
Published: July 2007

Background

Primary foci of necrobacillosis infection outside the head and neck are uncommon but have been reported in the urogenital or gastrointestinal tracts. Reports of infection with Solobacterium moorei are rare.

Case presentation

A 37-year-old male intravenous drug user was admitted with pain in his right groin, fever, rigors and vomiting following a recent injection into the right femoral vein. Admission blood cultures grew Fusobacterium nucleatum, Solobacterium moorei and Bacteroides ureolyticus. The patient was successfully treated with intravenous penicillin and metronidazole.

Conclusion

This case report describes an unusual case of femoral thrombophlebitis with septic pulmonary embolism associated with anaerobic organisms in a groin abscess. Solobacterium moorei, though rarely described, may also have clinically significant pathogenic potential.
Expert agreement confirms that negative changes in hand and foot radiographs are a surrogate for repair in patients with rheumatoid arthritis
Authors: van der Heijde Désirée , Landewé Robert , Boonen Annelies , Einstein Steve , Herborn Gertraud , Rau Rolf , Wassenberg Siegfried , Weissman Barbara N , Winalski Carl S , Sharp John T
Published: July 2007

The objective of the present study was to test the hypothesis that experts recognize repair of erosions and, if so, to determine which, if any, morphologic features permitted them to recognize the repair. We also tested whether scoring by a standard method detected repair. Seven experienced readers of radiographs in rheumatoid arthritis were presented with 64 sets of single joints-of-interest at two time points, randomized and blinded for the correct sequence. The readers assessed which joint was better, and recorded whether any of six specific features were seen. Two independent readers, experienced in scoring by the van der Heijde-modified Sharp method who were not on the expert panel, then scored the complete films that included the joint-of-interest. The panel agreed very well on which of two joints was better, and, even though they did not know the true sequence, the panel accurately assigned a sequence slightly better than chance alone (58%) but worse than their agreement on which image was 'better or worse' (78%). The readers therefore indirectly assigned repair by choosing the second film as the best. Putative repair features were seen in cases of both repair and progression, and were not discriminatory. Similar results were obtained when the experts were presented with the entire hand or foot containing the joint-of-interest. In the third repair exercise, two independent readers who scored whole hands and feet using a standard method found a mean negative score in 22/60 joints-of-interest. All 22 joints were also scored as repair by the panel. Repair was detected reliably by a majority of the panel on viewing paired images based on a better/worse decision and assigning sequence in a set of images that were blinded for sequence by an independent project manager. In this test set of images, repair was manifested by a reduction in the size of erosion in many cases. Size was one feature that aided the experts to detect repair but cannot be the only one; the experts had to find other features to determine whether a smaller erosion was the first in a sequence of radiographs in a patient with progressive damage or was the second film in a patient exhibiting repair. The change in size of erosion was also picked up by independent readers applying the van der Heijde-modified Sharp scoring method and was reflected in their scores.
A 30 ton biaxial tensile testing machine
Authors: Fessler H , Musson J K
Published: July 2007

The machine is intended for a flat-plate testpiece, one face of which has to be unobstucted throughout the test. Plates up to 36 in long, 27 in wide, and 3/4 in thick can be accommodated.

Hydraulic rams actuated by air-hydraulic pumps exert completely independent tensions on cruciform test pieces through spherical bushes.

Satisfactory direct-load readings were obtained form pressure gauges.
Finite-element stress analysis of a multi-piece piston
Authors: White D J , Enderby L R
Published: July 2007

The paper deals with calculations of temperatures and stresses in a three-piece piston made with the help of finite-element computer programmes and describes the special problems encountered in the stress analysis of multi-piece components. The piston was treated as an axi-symmetric body for both temperature and stress analysis.