bluuebunny/crossref_metadata_2025 huggingface dataset:
Get your Act Together
Authors: Ferrara Federico , Weishaupt J. Timo
Published: September 2004

Research on elections to the European Parliament (EP) has consistently found that European elections are distinguished by a lack of European content. Such elections, in spite of the growing powers exercised by the EP, remain ‘second-order’. Clearly, however, EU-related issues have affected the performance of some political parties in EP elections, particularly in countries such as Sweden and Denmark. In our empirical analysis of the three most recent EP elections, we explain party choice as a function of both European and non-EU-related factors. Through the use of standard regression models, we find that the parties that have not ‘got their act together’ on European issues—whose internal fractionalization leads to ambiguities about their stance on EU integration—systematically perform worse. We also corroborate some of the implications of the ‘second-order’ model and resolve some empirical disputes.
Public Opinion and Enlargement
Authors: Jones Erik , van der Bijl Niels
Published: September 2004

This paper examines European Union (EU) member state attitudes toward enlargement. We use Eurobarometer data for aggregate national support from 1996 to 2002 for the accession of each of 13 candidate countries—the 10 that will join the EU in 2004 plus Bulgaria, Romania, and Turkey. Analyzing our cross-section time series, we find, first, that the level of support correlates positively with the share of the candidate country in the total exports of the member state and negatively with the distance between the capitals of the member state and the candidate country. This finding supports the hypothesis that common identity, or ‘we-feeling,’ grows with interaction (Deutsch et al., 1957). Second, support correlates negatively with the relative importance of agriculture in domestic employment. Since agriculture triggers EU financial flows, this finding supports the view that attitudes toward integration are policy related (Gabel, 1998b, 1998c). Third, support is lower when both the member state and the candidate country are predominantly Catholic. This suggests that, although Catholics may desire a deeper Europe (Nelsen et al., 2001), they oppose a wider Europe.
Race and Ethnicity or Racialized Ethnicities?
Authors: Grosfoguel Ramán
Published: September 2004

The traditional distinction between race and ethnicity is considered highly problematic. In the literature, ethnicity is frequently assumed to be the cultural identity of a group within a nation state while race is assumed to be the biological and/or cultural essentialization/naturalization of a group based on a hierarchy of superiority and inferiority related to the biological constitution of their bodies. It is posited that, depending on the context of power relations involved, there are ‘racialized ethnicities’ and/or ‘ethnicized races.’ The racialization of Puerto Rican identity in New York City is an example of the former and the use of racial categories such as ‘black’ as an ethnic identity is an example of the latter. By using the notion of coloniality of power, this article attempts to justify the use of the notion ‘racial/ethnic identity’ rather than using these concepts as separate or autonomous categories.
Unyielding Positions
Authors: Kim Claire Jean
Published: September 2004

What are the implications of the social constructionist insight about race for the political struggle against racism? This question has sparked a vigorous cross-disciplinary debate. At issue is whether the struggle to contain the damage done by racism is best served by rejecting the concept of race altogether, rehabilitating it, or partially dismantling it. I aim to accomplish three tasks here. The first is to provide a much-needed overview of this debate about race and essentialism. Second, I advance a critique of this debate, arguing that the main participants in this debate commit a shared error: they implicitly advance a binary white/non-white framework that falsely homogenizes the experiences of non-white groups and obscures the fact that differential racialization processes have generated a complex structure of multiple group positions in American society. Finally, I conclude by considering what strategies progressive scholars might employ in challenging the differential positioning of racialized groups.
Law and Politics in Post-Modern California
Authors: Johnson Kevin R.
Published: September 2004

This article considers the future of relations between African Americans, Asian Americans, and Latina/os in the political process in the United States and evaluates the prospects for social change. To do so, this article focuses on Los Angeles, California, which for a number of years has experienced the demographic change that is beginning to be replicated across the nation. Particular attention is paid to interethnic conflict and the need to redefine the conventional ‘civil rights’ discourse to reflect the changing socio-economic landscape of postmodern California.
Racial Formation, Environmental Racism, and the Emergence of Silicon Valley
Authors: Park Lisa Sun-Hee , Pellow David N.
Published: September 2004

The environmental justice literature is characterized by a strange fact: the vast majority of research on this topic is about racial inequality, yet there is almost no mention of social scientific theories of race and racism. It is as if statistical correlations alone are enough to prove or disprove the existence of racism. While there are exceptions to this rule, the overwhelming majority of environmental justice studies make no mention of well-established theoretical frameworks on racism from the social sciences. This article is an effort to place the problem of environmental racism/inequality in the broader context of sociological theories of racism. To that end we focus on the theory of racial formation – specifically the concept of racial projects – and extend this model to the question of environmental racism. By applying this theoretical framework to the case of immigrants and people of color in Silicon Valley, we argue that institutional racism – as is the case with environmental racism – is a complex set of practices supported by the linked exploitation of people and natural resources. We draw on both the discursive and material/structural practices of racial projects in Silicon Valley’s long history of environmental and social justice struggles to illustrate how environmental racism functions within a racial formation framework.
The Notion of Modernity in 19th-Century Spain
Authors: Sebastián Javier Fernández , De Miguel Gonzalo Capellán
Published: September 2004

This article has two main aims. First, it provides a brief account of the terms modernidad (modernity) and modernismo (modernism) in the Spanish context from the end of the 18th century to the beginning of the 20th century. Second, it seeks to illustrate the way in which conceptual history is being approached in a Spanish context. It draws upon the collaborative efforts of a group of over 30 scholars who have sought to explore the political lexicon of 19th-century Spain. The article deploys the analytical categories and methodological tools associated with the followers of Begriffsgeschichte and of the Cambridge school. Our conclusion is that an examination of these two terms reveals that the emphasis upon Spanish singularity has been exaggerated and that, despite the historical backwardness of the country, Spain played an outstanding role in the creation of the language of modernity and postmodernity.
Foucault and Power Revisited
Authors: Widder Nathan
Published: September 2004

This article takes issue with interpretations of Foucault’s thought that understand power and resistance as forces working in opposition to one another to fix and dissolve or construct and deconstruct social identities. Starting from the theme of dispersion presented in The Archaeology of Knowledge, it maintains that, for Foucault, power works only in a dispersive manner and that identities are not so much substantialities produced by power as simulacra that appear on the surface of a very different dynamic. Resistance, in turn, is not a force opposed to power but rather a consequence of the disjunctive nature of power relations themselves. Using this reconceived dynamic of power and resistance, the article revisits Foucault’s understanding of disciplinary society and the micropolitics of the care of the self, and argues that, although Foucault has been deployed in political theory to show that identities are both necessary and problematic, his work in fact points to a politics and ethics that strives to dispense with this necessity altogether.
Communicative Power in Habermas’s Theory of Democracy
Authors: Flynn Jeffrey
Published: September 2004

This article critically examines Jürgen Habermas’s theory of democracy as developed in Between Facts and Norms. In particular, it focuses on the concept of communicative power and argues that there is a crucial ambiguity in Habermas’s use of this concept. Since communicative power is the key normative resource that is supposed to counter the norm-free steering media of money and administrative power, its role within the theory must be made clear. The article begins by explaining the normative and social-theoretic foundations of the theory. Then it highlights the normative importance of the public sphere in Habermas’s two-track model of deliberative politics, before turning to the problems with the concept of communicative power. Two alternative readings of its role are provided in order to demonstrate how it needs to be further clarified.
After chronic myelogenous leukemia: tyrosine kinase inhibitors in other hematologic malignancies
Authors: Wadleigh Martha , DeAngelo Daniel J. , Griffin James D. , Stone Richard M.
Published: September 2004

Tyrosine kinases phosphorylate proteins on tyrosine residues, producing a biologic signal that influences many aspects of cellular function including cell growth, proliferation, differentiation, and death. Constitutive or unregulated activity through mutation or overexpression of these enzymes is a common pathologic feature in many acute and chronic leukemias. Inhibition of tyrosine kinases represents a strategy to disrupt signaling pathways that promote neoplastic growth and survival in hematologic malignancies and likely in other neoplasias as well. This review focuses on tyrosine kinases that have been implicated in the pathogenesis of hematologic diseases other than chronic myelogenous leukemia and discusses the evidence for the use of small molecules to target these kinases.
Molecular analysis of a large cohort of patients with the hyper immunoglobulin M (IgM) syndrome
Authors: Lee Wen-I , Torgerson Troy R. , Schumacher Michael J. , Yel Leman , Zhu Qili , Ochs Hans D.
Published: September 2004

The hyper immunoglobulin M (IgM) syndrome (HIGM), characterized by recurrent infections, low serum IgG and IgA, normal or elevated IgM, and defective class switch recombination and somatic hypermutation, is a heterogenous disorder with at least 5 distinct molecular defects, including mutations of the genes coding for the CD40 ligand (CD40L) and IKK-gamma (NEMO) genes, both X-linked; and mutations of CD40, activation-induced cytidine deaminase (AICDA), and uracil-DNA glycosylase (UNG), associated with autosomal recessive HIGM syndromes. To investigate the molecular basis of HIGM, we determined the prevalence of mutations affecting these 5 genes in a cohort of 140 patients (130 males and 10 females). Those patients without a molecular diagnosis were subsequently evaluated for mutations of the following genes: inducible CO-stimulator molecule (ICOS), ICOS ligand (ICOSL), and if male, Bruton tyrosine kinase (Btk) and SLAM-associated protein (SAP/SH2D1A). We found mutations of CD40L in 98 males; AICDA in 4 patients (3 males, 1 female); UNG in one adult male; and Btk in 3 boys. Of the remaining 25 males, one infant with hypohidrotic ectodermal dysplasia had a mutation of NEMO. None of the remaining 33 patients (24 males/9 females) had mutations affecting CD40, ICOS, ICOSL, or SH2D1, and are best classified as common variable immune deficiency (CVID), although other genes, including some not yet identified, may be responsible.
Proinflammatory mediators elicit secretion of the intracellular B-lymphocyte stimulator pool (BLyS) that is stored in activated neutrophils: implications for inflammatory diseases
Authors: Scapini Patrizia , Carletto Antonio , Nardelli Bernardetta , Calzetti Federica , Roschke Viktor , Merigo Flavia , Tamassia Nicola , Pieropan Sara , Biasi Domenico , Sbarbati Andrea , Sozzani Silvano , Bambara Lisa , Cassatella Marco A.
Published: September 2004

We have recently shown that granulocyte–colony-stimulating factor (G-CSF)– and interferon-γ (IFN-γ)–activated human neutrophils accumulate and release remarkable amounts of soluble B-lymphocyte stimulator (BLyS) in vitro. In this study, we provide evidence that neutrophils migrating into skin window exudates (SWEs) developed in healthy volunteers and in patients with rheumatoid arthritis (RA), synthesized, and released BLyS in response to locally produced G-CSF. Accordingly, the concentrations of soluble BLyS in SWEs were significantly more elevated than in serum. Because the levels of SWE BLyS, but not SWE G-CSF, were higher in patients with RA than in healthy subjects, we examined the effect of CXCL8/IL-8, C5a, and other proinflammatory mediators that dramatically accumulate in RA SWEs and in inflamed synovial fluids. We show that CXCL1/GROα, CXCL8/IL-8, C5a, immune complexes, tumor necrosis factor-α (TNF-α), leukotriene B4, N-formyl-methionyl-leucyl-phenylalanine (fMLP), and lipopolysaccharide (LPS), which by themselves do not induce BLyS de novo synthesis, act as potent secretagogues for BLyS, which is mainly stored in Golgi-related compartments within G-CSF–treated neutrophils, as determined by immunogold electron microscopy. This action is pivotal in greatly amplifying neutrophil-dependent BLyS release in SWEs of patients with RA compared with healthy subjects. Collectively, our data uncover a novel mechanism that might dramatically exacerbate the release of BLyS by neutrophils during pathologic inflammatory responses.
Different steroids co-regulate long-term expansion versus terminal differentiation in primary human erythroid progenitors
Authors: Leberbauer Cornelia , Boulmé Florence , Unfried Gertrud , Huber Johannes , Beug Hartmut , Müllner Ernst W.
Published: September 2004

Outgrowth, long-term self-renewal, and terminal maturation of human erythroid progenitors derived from umbilical cord blood in serum-free medium can be modulated by steroid hormones. Homogeneous erythroid cultures, as characterized by flow cytometry and dependence on a specific mixture of physiologic proliferation factors, were obtained within 8 days from a starting population of mature and immature mononuclear cells. Due to previous results in mouse and chicken erythroblasts, the proliferation-promoting effect of glucocorticoids was not unexpected. Surprisingly, however, androgen had a positive effect on the sustained expansion of human female but not male erythroid progenitors. Under optimal conditions, sustained proliferation of erythroid progenitors resulted in a more than 109-fold expansion within 60 days. Terminal erythroid maturation was significantly improved by adding human serum and thyroid hormone (3,5,3′-triiodothyronine [T3]) to the differentiation medium. This resulted in highly synchronous differentiation of the cells toward enucleated erythrocytes within 6 days, accompanied by massive size decrease and hemoglobin accumulation to levels comparable to those in peripheral blood erythrocytes. Thus, obviously, different ligand-activated nuclear hormone receptors massively influence the decision between self-renewal and terminal maturation in the human erythroid compartment.
Prediction of T-cell reconstitution by assessment of T-cell receptor excision circle before allogeneic hematopoietic stem cell transplantation in pediatric patients
Authors: Chen Xiaohua , Barfield Raymond , Benaim Ely , Leung Wing , Knowles James , Lawrence Dawn , Otto Mario , Shurtleff Sheila A. , Neale Geoffrey A. M. , Behm Frederick G. , Turner Victoria , Handgretinger Rupert
Published: September 2004

The extent and rapidity with which T cells are regenerated from graft-derived precursor cells directly influences the incidence of infection and the T-cell–based graft-versus-tumor effect. Measurement of T-cell receptor excision circles (TRECs) in peripheral blood is a means of quantifying recent thymic T-cell production and has been used after transplantation in many studies to estimate thymus-dependent T-cell reconstitution. We hypothesized that the quality of thymic function before transplantation affects thymus-dependent T-cell reconstitution after transplantation. We used real-time polymerase chain reaction (PCR) to quantify signal-joint TRECs (sjTRECs) before and after transplantation. T-cell reconstitution was evaluated by T-cell receptor β (TCRβ) CDR3 size spectratyping. We tested 77 healthy sibling donors and 244 samples from 26 pediatric recipients of allogeneic hematopoietic stem cell transplantation (AHSCT). Blood from the healthy donors contained 1200 to 155 000 sjTREC copies/mL blood. Patients who had greater than 1200 copies/mL blood before transplantation showed early recovery of sjTREC numbers and TCRβ repertoire diversity. In contrast, patients who had fewer than 1200 copies/mL blood before transplantation demonstrated significantly slower restoration of thymus-dependent T cells. We conclude that the rate of reconstitution of thymus-dependent T cells is dependent on the competence of thymic function in the recipients before transplantation. Therefore, pretransplantation measurement of sjTREC may provide an important tool for predicting thymus-dependent T-cell reconstitution after transplantation.
High incidence of occult leptomeningeal disease detected by flow cytometry in newly diagnosed aggressive B-cell lymphomas at risk for central nervous system involvement: the role of flow cytometry versus cytology
Authors: Hegde Upendra , Filie Armando , Little Richard F. , Janik John E. , Grant Nicole , Steinberg Seth M. , Dunleavy Kieron , Jaffe Elaine S. , Abati Andrea , Stetler-Stevenson Maryalice , Wilson Wyndham H.
Published: September 2004

We assessed the cerebrospinal fluid (CSF) by flow cytometry and cytology in 51 newly diagnosed and 9 treated aggressive B-cell lymphomas at risk for central nervous system (CNS) involvement to examine the utility of flow cytometry, incidence of CSF disease, and clinical surrogates of CNS spread. Multicolor flow cytometry using multiple antibody panels for light chains and B- and T-cell antigens identified neoplastic clones that constituted as little as 0.2% of total CSF lymphocytes. Among 51 newly diagnosed patients, 11 (22%) had occult CSF involvement. All 11 were detected by flow cytometry but only 1 by cytology (P = .002). Among 9 treated patients, CSF involvement was detected by flow cytometry alone in 2 and also by cytology in 1 case. CSF chemistry and cell counts were similar in patients with and without CSF lymphoma. Only the number of extranodal sites was associated with occult CSF lymphoma in newly diagnosed patients by univariate (P = .006) or logistic regression analysis (P = .012). We hypothesize that the biologic phenotype associated with colonization of extranodal sites leads to CNS spread, possibly related to the microenvironment. Patients at risk for CNS spread should undergo staging CSF evaluation by flow cytometry.
A polymorphism in the VKORC1 gene is associated with an interindividual variability in the dose-anticoagulant effect of warfarin
Authors: D'Andrea Giovanna , D'Ambrosio Rosa Lucia , Di Perna Pasquale , Chetta Massimiliano , Santacroce Rosa , Brancaccio Vincenzo , Grandone Elvira , Margaglione Maurizio
Published: September 2004

Patients require different warfarin dosages to achieve the target therapeutic anticoagulation. The variability is largely genetically determined, and it can be only partly explained by genetic variability in the cytochrome CYP2C9 locus. In 147 patients followed from the start of anticoagulation with warfarin, we have investigated whether VKORC1 gene mutations have affected doses of drug prescribed to acquire the target anticoagulation intensity. Two synonymous mutations, 129C>T at Cys43 and 3462C>T at Leu120, and 2 missense mutations, Asp38Tyr and Arg151Gln, were identified. None of these mutations was found to affect the interindividual variability of warfarin prescribed. Finally, 2 common polymorphisms were found, 1173C>T in the intron 1 and 3730G>A transition in the 3′ untranslated region (UTR). Regardless of the presence of confounding variables, the mean adjusted dose required of warfarin was higher (6.2 mg) among patients with the VKORC1 1173CC genotype than those of patients carrying the CT (4.8 mg; P = .002) or the TT genotype (3.5 mg; P < .001). In the present setting, VKORC1 and CYP2C9 genetic variants investigated accounted for about a third (r2, 0.353) of the interindividual variability. Genetic variants of the VKORC1 gene locus modulate the mean daily dose of drug prescribed to acquire the target anticoagulation intensity.
Combination immunotherapy with a CpG oligonucleotide (1018 ISS) and rituximab in patients with non-Hodgkin lymphoma: increased interferon-α/β–inducible gene expression, without significant toxicity
Authors: Friedberg Jonathan W. , Kim Helen , McCauley Mary , Hessel Edith M. , Sims Paul , Fisher David C. , Nadler Lee M. , Coffman Robert L. , Freedman Arnold S.
Published: September 2004

CpG oligodeoxynucleotides (CpG-ODNs) affect innate and adaptive immune responses, including antigen presentation, costimulatory molecule expression, dendritic cell maturation, and induction of cytokines enhancing antibody-dependent cell-mediated cytotoxicity (ADCC). We conducted a phase 1 study evaluating 4 dose levels of a CpG-ODN (1018 ISS) with rituximab in 20 patients with relapsed non-Hodgkin lymphoma (NHL). Patients received CpG once a week for 4 weeks beginning after the second of 4 rituximab infusions. Adverse events were minimal. Quantitative polymerase chain reaction (PCR) measurements of a panel of genes inducible by CpG-ODN and interferons were performed on blood samples collected before and 24 hours after CpG. A dose-related increase was measured in the expression of several interferon–inducible genes after CpG and correlated with serum levels of 2′-5′ oligoadenylate synthetase (OAS), a validated interferon response marker. Genes induced selectively by interferon-γ (IFN-γ) were not significantly induced by CpG. In conclusion, we have defined a set of gene expression markers that provide a sensitive measure of biologic responses of patients to CpG therapy in a dose-related manner. Moreover, all the genes significantly induced by this CpG are regulated by type 1 interferons, providing insight into the dominant immune mechanisms in humans. CpG treatment resulted in no significant toxicity, providing rationale for further testing of this exciting combination immunotherapy approach to NHL.
Murine embryonic stem cell differentiation is promoted by SOCS-3 and inhibited by the zinc finger transcription factor Klf4
Authors: Li Yanjun , McClintick Jeanette , Zhong Li , Edenberg Howard J. , Yoder Mervin C. , Chan Rebecca J.
Published: September 2004

Embryonic stem (ES) cells homozygous for a Shp-2 mutation (Shp-2Δ46-110) demonstrate leukemia inhibitory factor (LIF) hypersensitivity and increased LIF-stimulated phosphorylation of signal transducer and activator of transcription (STAT3). We hypothesized that LIF-responsive genes in Shp-2Δ46-110 cells would represent potential candidates for molecules vital for ES cell self-renewal. Using microarray analysis, we detected 41 genes whose expression was modified by LIF in Shp-2Δ46-110 ES cells. Induction of 2 significantly up-regulated genes, suppressor of cytokine signaling–3 (SOCS-3) and Krüppel-like factor 4 (Klf4), was verified using Northern blotting. ES cells overexpressing SOCS-3 had an increased capacity to differentiate to hematopoietic progenitors, rather than to self-renew. In contrast, ES cells overexpressing Klf4 had a greater capacity to self-renew based on secondary embryoid body (EB) formation. Klf4-transduced d6 EBs expressed higher levels of Oct-4, consistent with the notion that Klf4 promotes ES cell self-renewal. These findings verify the negative role of SOCS-3 on LIF signaling and provide a novel role for Klf4 in ES cell function.
Acquired α-thalassemia in association with myelodysplastic syndrome and other hematologic malignancies
Authors: Steensma David P. , Gibbons Richard J. , Higgs Douglas R.
Published: September 2004

Abnormalities of hemoglobin synthesis are usually inherited but may also arise as a secondary manifestation of another disease, most commonly hematologic neoplasia. Acquired hemoglobin disorders can be seen in any population and are not restricted to areas of the world with high incidences of inherited hemoglobinopathies. In fact, the acquired hemoglobinopathies may be more readily recognized where inherited hemoglobin abnormalities are rare and less likely to cause diagnostic confusion. Acquired α-thalassemia is the best characterized of the acquired red blood cell disorders in patients with hematologic malignancy, and it is almost always associated with a myelodysplastic syndrome (MDS). At least 2 molecular mechanisms for acquired α-thalassemia are now recognized: acquired deletion of the α-globin gene cluster limited to the neoplastic clone and, more commonly, inactivating somatic mutations of the trans-acting chromatin-associated factor ATRX, which cause dramatic down-regulation of α-globin gene expression. Here we review the clinical, hematologic, and molecular genetic features of α-thalassemia arising in a clonal myeloid disorder, and we discuss howATRX might affect gene expression in normal and abnormal hematopoiesis through epigenetic mechanisms.
Antroduodenal motility in neurologically handicapped children with feeding intolerance
Authors: Werlin Steven L
Published: September 2004

Background

Dysphagia and feeding intolerance are common in neurologically handicapped children. The aim is to determine the etiologies of feeding intolerance in neurologically handicapped children who are intolerant of tube feedings.

Methods

Eighteen neurologically handicapped children, followed in the Tube Feeding Clinic at the Children's Hospital of Wisconsin who were intolerant of gastrostomy feedings. The charts of these 18 patients were reviewed. Past medical history, diagnoses, history of fundoplication and results of various tests of gastrointestinal function including barium contrast radiography, endoscopy and antroduodenal manometry were documented.

Results

Five of 11 children had abnormal barium upper gastrointestinal series. Seven of 14 had abnormal liquid phase gastric emptying tests. Two of 16 had esophagitis on endoscopy. All 18 children had abnormal antroduodenal motility.

Conclusions

In neurologically handicapped children foregut dysmotility may be more common than is generally recognized and can explain many of the upper gastrointestinal symptoms in neurologically handicapped children.
Glutamine-enriched enteral nutrition in very low birth weight infants. Design of a double-blind randomised controlled trial [ISRCTN73254583]
Authors: van den Berg Anemone , van Elburg Ruurd M , Twisk Jos WR , Fetter Willem PF
Published: September 2004

Background

Enteral feeding of very low birth weight (VLBW) infants is a challenge, since metabolic demands are high and administration of enteral nutrition is limited by immaturity of the gastrointestinal tract. The amino acid glutamine plays an important role in maintaining functional integrity of the gut. In addition, glutamine is utilised at a high rate by cells of the immune system. In critically ill patients, glutamine is considered a conditionally essential amino acid. VLBW infants may be especially susceptible to glutamine depletion as nutritional supply of glutamine is limited in the first weeks after birth. Glutamine depletion has negative effects on functional integrity of the gut and leads to immunosuppression. This double-blind randomised controlled trial is designed to investigate the effect of glutamine-enriched enteral nutrition on feeding tolerance, infectious morbidity and short-term outcome in VLBW infants. Furthermore, an attempt is made to elucidate the role of glutamine in postnatal adaptation of the gut and modulation of the immune response.

Methods

VLBW infants (gestational age <32 weeks and/or birth weight <1500 g) are randomly allocated to receive enteral glutamine supplementation (0.3 g/kg/day) or isonitrogenous placebo supplementation between day 3 and 30 of life. Primary outcome is time to full enteral feeding (defined as a feeding volume ≥ 120 mL/kg/day). Furthermore, incidence of serious infections and short-term outcome are evaluated. The effect of glutamine on postnatal adaptation of the gut is investigated by measuring intestinal permeability and determining faecal microflora. The role of glutamine in modulation of the immune response is investigated by determining plasma Th1/Th2 cytokine concentrations following in vitro whole blood stimulation.
The Internet and HIV study: design and methods
Authors: Elford Jonathan , Bolding Graham , Davis Mark , Sherr Lorraine , Hart Graham
Published: September 2004

Background

The Internet provides a new meeting ground, especially for gay men, that did not exist in the early 1990s. Several studies have found increased levels of high risk sexual behaviour and sexually transmissible infections (STI) among gay men who seek sex on the Internet, although the underlying processes are not fully understood. Research funded by the UK Medical Research Council (2002–2004) provided the opportunity to consider whether the Internet represents a new sexual risk environment for gay and bisexual men living in London.

Methods

The objectives of the Internet and HIV study are to: (i) measure the extent to which gay men living in London seek sexual partners on the Internet; (ii) compare the characteristics of London gay men who do and do not seek sex on the Internet; (iii) examine whether sex with Internet-partners is less safe than with other sexual partners; (iv) compare use of the Internet with other venues where men meet sexual partners; (v) establish whether gay men use the Internet to actively seek partners for unprotected anal intercourse; (vi) determine the potential for using the Internet for HIV prevention. These objectives have been explored using quantitative and qualitative research methods in four samples of London gay men recruited and interviewed both online and offline. The four samples were: (i) gay men recruited through Internet chat rooms and profiles; (ii) HIV positive gay men attending an NHS hospital outpatients clinic; (iii) gay men seeking an HIV test in an NHS HIV testing or sexual health clinic; (iv) gay men recruited in the community.

Results

Quantitative data were collected by means of confidential, anonymous self-administered questionnaires (n>4000) completed on-line by the Internet sample. Qualitative data were collected by means of one-to-one interviews (n = 128) conducted either face-to-face or on-line.

Conclusion

The strength of the Internet and HIV study is its methodological plurality, drawing on both qualitative and quantitative research among online and offline samples, as well as taking advantage of recent advances in web survey design. The study's findings will help us better understand the role of the Internet in relation to gay men's sexual practice
Multi-line split DNA synthesis: a novel combinatorial method to make high quality peptide libraries
Authors: Tabuchi Ichiro , Soramoto Sayaka , Ueno Shingo , Husimi Yuzuru
Published: September 2004

Background

We developed a method to make a various high quality random peptide libraries for evolutionary protein engineering based on a combinatorial DNA synthesis.

Results

A split synthesis in codon units was performed with mixtures of bases optimally designed by using a Genetic Algorithm program. It required only standard DNA synthetic reagents and standard DNA synthesizers in three lines. This multi-line split DNA synthesis (MLSDS) is simply realized by adding a mix-and-split process to normal DNA synthesis protocol. Superiority of MLSDS method over other methods was shown. We demonstrated the synthesis of oligonucleotide libraries with 1016 diversity, and the construction of a library with random sequence coding 120 amino acids containing few stop codons.

Conclusions

Owing to the flexibility of the MLSDS method, it will be able to design various "rational" libraries by using bioinformatics databases.
Rapid and reliable extraction of genomic DNA from various wild-type and transgenic plants
Authors: Kang Tae-Jin , Yang Moon-Sik
Published: September 2004

Background

DNA extraction methods for PCR-quality DNA from calluses and plants are not time efficient, since they require that the tissues be ground in liquid nitrogen, followed by precipitation of the DNA pellet in ethanol, washing and drying the pellet, etc. The need for a rapid and simple procedure is urgent, especially when hundreds of samples need to be analyzed. Here, we describe a simple and efficient method of isolating high-quality genomic DNA for PCR amplification and enzyme digestion from calluses, various wild-type and transgenic plants.

Results

We developed new rapid and reliable genomic DNA extraction method. With our developed method, plant genomic DNA extraction could be performed within 30 min. The method was as follows. Plant tissue was homogenized with salt DNA extraction buffer using hand-operated homogenizer and extracted by phenol:chloroform:isoamyl alcohol (25:24:1). After centrifugation, the supernatant was directly used for DNA template for PCR, resulting in successful amplification for RAPD from various sources of plants and specific foreign genes from transgenic plants. After precipitating the supernatant, the DNA was completely digested by restriction enzymes.

Conclusion

This DNA extraction procedure promises simplicity, speed, and efficiency, both in terms of time and the amount of plant sample required. In addition, this method does not require expensive facilities for plant genomic DNA extraction.
Comparison of the NEI-VFQ and OSDI questionnaires in patients with Sjögren's syndrome-related dry eye
Authors: Vitale Susan , Goodman Linda A , Reed George F , Smith Janine A
Published: September 2004

Background

To examine the associations between vision-targeted health-related quality of life (VT-HRQ) and ocular surface parameters in patients with Sjögren's syndrome, a systemic autoimmune disease characterized by dry eye and dry mouth.

Methods

Forty-two patients fulfilling European / American diagnostic criteria for Sjögren's syndrome underwent Schirmer testing without anesthesia, ocular surface vital dye staining; and measurement of tear film breakup time (TBUT). Subjects were administered the Ocular Surface Disease Index (OSDI) and the 25-item National Eye Institute Vision Functioning Questionnaire (NEI-VFQ). Main outcome measures included ocular surface parameters, OSDI subscales describing ocular discomfort (OSDI-symptoms), vision-related function (OSDI-function), and environmental triggers, and NEI-VFQ subscales.

Results

Participants (aged 31–81 y; 95% female) all had moderate to severe dry eye. Associations of OSDI subscales with the ocular parameters were modest (Spearman r (ρ) < 0.22) and not statistically significant. Associations of NEI-VFQ subscales with the ocular parameters reached borderline significance for the near vision subscale with TBUT (ρ = 0.32, p = .05) and for the distance vision subscale with van Bijsterveld score (ρ = 0.33, p = .04). The strongest associations of the two questionnaires were for: ocular pain and mental function with OSDI-symptoms (ρ = 0.60 and 0.45, respectively); and general vision, ocular pain, mental function, role function, and driving with OSDI-function (ρ = 0.60, 0.50, 0.61, 0.64, 0.57, and 0.67, respectively).

Conclusions

Associations between conventional objective measures of dry eye and VT-HRQ were modest. The generic NEI-VFQ was similar to the disease-specific OSDI in its ability to measure the impact of Sjögren's syndrome-related dry eye on VT-HRQ.
Predictors of vigorous exercise adoption and maintenance over four years in a community sample
Authors: Boutelle Kerri N , Jeffery Robert W , French Simone A
Published: September 2004

Background

Very little is known about the correlates of adoption and maintenance of vigorous exercise. The purpose of this study was to understand the sociodemographic correlates of exercise adoption and maintenance in a community sample.

Methods

917 women and 229 men completed annual surveys as part of a community-based weight gain prevention trial over four years. Multivariate regressions evaluated predictive factors for maintenance of vigorous exercise over time in regular exercisers, and predictors of adoption of exercise in adults who were sedentary at baseline.

Results

Exercise maintenance at Years 2 and 3 was associated with ethnicity and exercise level at baseline, while exercise maintenance at Year 4 was associated with television watching, BMI and exercise at baseline. Exercise level at baseline was associated with exercise initiation at Year 2 and Year 3. Income level, marital status, and smoking status predicted exercise initiation at Year 4.

Conclusions

Predictors of vigorous exercise maintenance were more consistent than predictors of vigorous exercise initiation. Results suggest that those who adopt vigorous exercise are a heterogeneous group and intervention messages could be more broadly focused. These data also suggest that exercise maintenance interventions should continue to target low-income populations with messages regarding smoking, weight and television. Clearly further research is needed to understand the factors that contribute to exercise initiation and maintenance, and to develop effective interventions to improve levels of physical activity levels.
Coexpression of Corticotropin-Releasing Hormone and Urotensin I Precursor Genes in the Caudal Neurosecretory System of the Euryhaline Flounder (Platichthys flesus): A Possible Shared Role in Peripheral Regulation
Authors: Lu Weiqun , Dow Louise , Gumusgoz Sarah , Brierley Matthew J. , Warne Justin M. , McCrohan Catherine R. , Balment Richard J. , Riccardi Daniela
Published: September 2004

CRH and urotensin I (UI) are neuroendocrine peptides that belong to the superfamily of corticotropin-releasing factors. In mammals, these peptides regulate the stress response and other central nervous system functions, whereas in fish an involvement for UI in osmoregulation has also been suggested. We have identified, characterized, and localized the genes encoding these peptides in a unique fish neuroendocrine organ, the caudal neurosecretory system (CNSS). The CRH and UI precursors, isolated from a European flounder CNSS library, consist of 168 and 147 amino acid residues, respectively, with an overall homology of approximately 50%. Both precursors contain a signal peptide, a divergent cryptic region and a 41-amino acid mature peptide with cleavage and amidation sites. Genomic organization showed that whole CRH and UI coding sequences are contained in a single exon. Northern blot analysis and quantitative PCR of a range of tissues confirmed the CNSS as a major site of expression of both CRH and UI and thus serves as a likely source of circulating peptides. In situ hybridization demonstrated that CRH and UI colocalize to the same cells of the CNSS. Our findings suggest that, in euryhaline fish, the CNSS is a major site of production of CRH and probably contributes to the high circulating levels observed in response to specific environmental challenges. Furthermore, the localization of CRH and UI within the same cell population suggests an early, possibly shared role for these peptides in controlling stress-mediated adaptive plasticity.
Differential Signal Transduction of Progesterone and Medroxyprogesterone Acetate in Human Endothelial Cells
Authors: Simoncini Tommaso , Mannella Paolo , Fornari Letizia , Caruso Antonella , Willis Monica Y. , Garibaldi Silvia , Baldacci Chiara , Genazzani Andrea R.
Published: September 2004

The conjugated equine estrogens-only arm of the Women’s Health Initiative trial, showing a trend toward protection from heart disease as opposed to women receiving also medroxyprogesterone acetate (MPA), strengthens the debate on the cardiovascular effects of progestins. We compared the effects of progesterone (P) or MPA on the synthesis of nitric oxide and on the expression of leukocyte adhesion molecules, characterizing the signaling events recruited by these compounds. Although P significantly increases nitric oxide synthesis via transcriptional and nontranscriptional mechanisms, MPA is devoid of such effects. Moreover, when used together with physiological estradiol (E2) concentrations, P potentiates E2 effects, whereas MPA impairs E2 signaling. These findings are observed both in isolated human endothelial cells as well as in vivo, in ovariectomized rat aortas. A marked difference in the recruitment of MAPK and phosphatidylinositol-3 kinase explains the divergent effects of the two gestagens. In addition, both P and MPA decrease the adhesiveness of endothelial cells for leukocytes when given alone or with estrogen. MPA is more potent than P in inhibiting the expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1. However, when administered together with physiological amounts of glucocorticoids, MPA (which also binds glucocorticoid receptor) markedly interferes with the hydrocortisone-dependent stabilization of the transcription factor nuclear factor κB and with the expression of adhesion molecules, acting as a partial glucocorticoid receptor antagonist. Our findings show significant differences in the signal transduction pathways recruited by P and MPA in endothelial cells, which may have relevant clinical implications.
Activation of the Glucocorticoid Receptor or Liver X Receptors Interferes with Growth Hormone-Induced akr1b7 Gene Expression in Rat Hepatocytes
Authors: Kotokorpi Pia , Gardmo Cissi , Nyström C. Staffan , Mode Agneta
Published: September 2004

The akr1b7 gene encodes an aldo-keto reductase involved in detoxification of isocaproaldehyde, the product from side chain cleavage of cholesterol, and of 4-hydroxynonenal (4-HNE) formed by lipid peroxidation and cleavage. Here we show that the expression of akr1b7 mRNA in rat liver is sexually differentiated, expressed in females but not in males, and regulated by the sexually dimorphic secretion pattern of GH. A GH dose-dependent induction of akr1b7 was demonstrated in cultured primary rat hepatocytes, which was sensitive to cycloheximide. Activation of the glucocorticoid receptor (GR) or liver X receptors (LXR) by dexamethasone (Dex) and T1317, respectively, attenuated the GH-induced expression of akr1b7 and CYP2C12, the prototypical rat hepatic gene dependent on the female-characteristic secretion pattern of GH. In contrast, neither Dex nor T1317 had any repressive effect on the GH induction of IGF-I mRNA. A common mechanism for LXR- and GR-mediated repressive actions on gene transcription is inhibition of nuclear factor (NF)-κB; however, EMSAs and pharmacological interference with NF-κB signaling provided no evidence for the involvement of NF-κB in the repressive action of Dex and T1317 on GH-induced akr1b7 expression.
Regulation of 5α-Reductase Isoforms by Oxytocin in the Rat Ventral Prostate
Authors: Assinder S. J. , Johnson C. , King K. , Nicholson H. D.
Published: September 2004

Oxytocin (OT) is present in the male reproductive tract, where it is known to modulate contractility, cell growth, and steroidogenesis. Little is known about how OT regulates these processes. This study describes the localization of OT receptor in the rat ventral prostate and investigates if OT regulates gene expression and/or activity of 5α-reductase isoforms I and II. The ventral prostates of adult male Wistar rats were collected following daily sc administration of saline (control), OT, a specific OT antagonist or both OT plus antagonist for 3 d. Expression of the OT receptor was identified in the ventral prostate by RT-PCR and Western blot, and confirmed to be a single active binding site by radioreceptor assay. Immunohistochemistry localized the receptor to the epithelium of prostatic acini and to the stromal tissue. Real-time RT-PCR determined that OT treatment significantly reduced expression of 5α-reductase I but significantly increased 5α-reductase II expression in the ventral prostate. Activity of both isoforms of 5α-reductase was significantly increased by OT, resulting in increased concentration of prostatic dihydrotestosterone. In conclusion, OT is involved in regulating conversion of testosterone to the biologically active dihydrotestosterone in the rat ventral prostate. It does so by differential regulation of 5α-reductase isoforms I and II.
Gene Expression Profiling Identifies a Unique Androgen-Mediated Inflammatory/Immune Signature and a PTEN (Phosphatase and Tensin Homolog Deleted on Chromosome 10)-Mediated Apoptotic Response Specific to the Rat Ventral Prostate
Authors: Desai Kartiki V. , Michalowska Aleksandra M. , Kondaiah Paturu , Ward Jerrold M. , Shih Joanna H. , Green Jeffrey E.
Published: September 2004

Understanding androgen regulation of gene expression is critical for deciphering mechanisms responsible for the transition from androgen-responsive (AR) to androgen-independent (AI) prostate cancer (PCa). To identify genes differentially regulated by androgens in each prostate lobe, the rat castration model was used. Microarray analysis was performed to compare dorsolateral (DLP) and ventral prostate (VP) samples from sham-castrated, castrated, and testosterone-replenished castrated rats. Our data demonstrate that, after castration, the VP and the DLP differed in the number of genes with altered expression (1496 in VP vs. 256 in DLP) and the nature of pathways modulated. Gene signatures related to apoptosis and immune response specific to the ventral prostate were identified. Microarray and RT-PCR analyses demonstrated the androgen repression of IGF binding protein-3 and -5, CCAAT-enhancer binding protein-δ, and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) genes, previously implicated in apoptosis. We show that PTEN protein was increased only in the luminal epithelial cells of the VP, suggesting that it may be a key mediator of VP apoptosis in the absence of androgens. The castration-induced immune/inflammatory gene cluster observed specifically in the VP included IL-15 and IL-18. Immunostaining of the VP, but not the DLP, showed an influx of T cells, macrophages, and mast cells, suggesting that these cells may be the source of the immune signature genes. Interestingly, IL-18 was localized mainly to the basal epithelial cells and the infiltrating macrophages in the regressing VP, whereas IL-15 was induced in the luminal epithelium. The VP castration model exhibits immune cell infiltration and loss of PTEN that is often observed in progressive PCa, thereby making this model useful for further delineation of androgen-regulated gene expression with relevance to PCa.