bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative analysis of the ability of leucocytes, endothelial cells and platelets to degrade the subendothelial basement membrane: Evidence for cytokine dependence and detection of a novel sulfatase
Authors: BARTLETT MARK R. , UNDERWOOD PATRICIA A. , PARISH CHRISTOPHER R. 
Published: July 2007

SummaryThe subendothelial basement membrane (BM) is regarded as an important barrier to the entry of leucocytes into inflammatory sites. This study compares the ability of leucocytes, platelets and endothelial cells (EC) to degrade a [35SO4]‐labelled subendothelial extracellular matrix (ECM) and assesses the effect of PMA and various pro‐inflammatory cytokines on this degradative activity. The different products of degradation, identified by fast protein liquid chromatography (FPLC) gel filtration chromatography, were indicative of protease, endoglycosidase (heparanase) and exoglycosidase and/or sulfatase activity. In terms of FCM degradation, EC and platelets were the most active, with PMA stimulation further enhancing the degradative activity of these two cell types. Platelets exhibited predominantly heparanase activity whereas the FC degradation products suggested a range of enzymic activities, namely proteases, heparanases and sulfatases. Interestingly, EC in suspension expressed these three enzymic activities whereas confluent EC monolayers only exhibited sulfatase activity, suggesting that the former situation might represent an angiogenic response. In the case of leucocytes, neutrophils and lymphocytes degraded the ECM to a much greater extent than monocytes. Each cell type also differed in the predominant enzymic activities it expressed, for example, heparanase activity by lymphocytes, protease activity by neutrophils and sulfatase activity by monocytes. Furthermore, PMA stimulation was shown to have differential effects on these enzymic activities.Some pro‐inflammatory cytokines were found to be cell‐type specific in their effects on ECM degradation. Thus, lL‐1 + TNF enhanced neutrophil and EC degradation of the ECM but inhibited lymphocyte ECM degradation. In contrast, the chemokine IL‐8 enhanced ECM degradation by neutrophils, lymphocytes and EC. Of particular interest was the unique sulfatase activity expressed by EC and monocytes which was induced in FC by TNF + IL‐1 and IL‐8, whereas in monocytes the sulfatase activity was exclusively induced by the chemokine monocyte chemotactic and activating factor (MCAF).Collectively, the results of this study show that leucocytes differ markedly in the enzymes they express to degrade the BM during extravasation and that PMA and cytokines are cell‐type specific in their induction of hydrolytic enzyme activity. These results also indicate that EC may play an important role, not only in the recruitment of leucocytes, but also via sulfatase activity in the preparation of vascular BM for leucocyte extra vasion.
Feedback suppression of B cell colony formation by supernatants of B colony cells: Role of immunoglobulin
Authors: FERNANDEZ L. A. , MACSWEEN J. M. , FALLOWS G. , ROBSON D. A. 
Published: July 2007

SummaryWe have reported previously that CD5+ B cells from mature B cell colonies provide a negative feedback signal to the growth of autologous B cell colonies. Now we have observed that supernatants from mature B cell colonies also provide a negative feedback signal to the growth of autologous B cell colonies. We investigated the mechanism of this effect by growing B cell colonies physically separated by a 0.45 μm filter from T cells in millicell‐CM chambers. Addition of colony supernatants to the T cell compartment reduced the number of B cell colonies by 28±6%. Colony numbers were reduced by 11±2 and 17±5% when the supernatants were added to the B cell or to both compartments, respectively. Pulsing T cells with the B cell colony supernatants before adding them to the colonies also decreased colony numbers by 33 ± 13%.The addition of exogenous Ig classes and IgG subclasses to B cells decreased B cell colony numbers, although the effect was variable. In the presence of T cells, IgG had the greatest suppressive activity and the subclass IgG4 was most suppressive. In the absence of T cells, high concentrations of IgG almost abolished B cell colony formation.We conclude that these supernatants provide a negative feedback signal either directly to B cells, or via T cells which may be mediated at least in part by Ig.
The trouble with transgenic mice
Authors: SINCLAIR NICHOLAS R. StC. 
Published: July 2007

SummaryObservations on many antigen‐receptor transgenic models with anti‐self specificities have been interpreted as proof for clonal deletion or for mechanisms involved in clonal deletion. At the same time, there is increasing evidence that many lymphocytes that recognize self exist, are activated and produce end products, even in individuals without clinical autoimmunity. Except perhaps for the amount of anti‐self activity, there is little agreement on what distinguishes immune products normally recognizing self from those associated with clinical autoimmunity. To resolve this paradox, the tendency in immunology is to accept conclusions from transgenic models as normal, while judging those from the unmanipulated state as suspect. However, transgenics have a major weakness. Transgenes encoding antigen‐receptors are derived from highly selected mature lymphocytes and are expressed in developing lymphocytes that normally do not display the antigen‐receptors of mature lymphocytes. Such precocious expression of antigen‐receptors could have profound abnormal effects on lymphocyte development. Other transgenic models suggest that processes in lymphocyte differentiation not involving antigen‐receptor binding specificity exert powerful influences on lymphocyte development; therefore, mechanisms other than classical positive and negative selection are important.
Tissue expression, structure and function of the murine Ly‐6 family of molecules
Authors: GUMLEY THOMAS P , MCKENZIE IAN FC , SANDRIN MAURO S 
Published: July 2007

SummaryMurine Ly‐6 molecules are a family of cell surface glycoproteins which have interesting patterns of tissue expression during haematopoiesis from multipotential stem cells to lineage committed precursor cells, and on specific leucocyte subpopulations in the peripheral lymphoid tissues. These interesting patterns of tissue expression suggest an intimate association between the regulation of Ly‐6 expression and the development and homeostasis of the immune system. Ly‐6 molecules are low molecular weight phosphatidyl inositol anchored glycoproteins with remarkable amino acid homology throughout a distinctive cysteine rich protein domain that is associated predominantly with O‐linked carbohydrate. These molecules are encoded by multiple tightly linked genes located on Chr. 15 which have conserved geneomic organization. The in vivo functions of Ly‐6 molecules are not known although in vitro studies suggest a role in cellular activation. This review will summarize our understanding of Ly‐6 with regard to tissue expression, molecular structure, gene organization and function.
Cytokine mediated effects in mucosal immunity
Authors: KRAMER DAVID R , SUTHERLAND ROBYN M , BAO SHISAN , HUSBAND ALAN J 
Published: July 2007

SummaryThe predominance of IgA antibodies in mucosal sites reflects a combination of high rate IgA isotype switching among precursor cells in induction sites, their selective localization in mucosal effector tissues and vigorous proliferation of these cells after extravasation. Each of these steps leading to IgA expression at the mucosa is under cytokine control. This paper will address the role of cytokines in induction and expression of IgA responses and strategies for manipulating cytokine expression. Therapeutic interventions based on this information may not only lead to improved vaccination responses and correction of immunodeficiencies but also, by invoking the phenomenon of oral tolerance, may assist in the management of autoimmune, allergic and alloreactive disease.
Histopathology of the lung following intratracheal challenge with live Pseudomonas aeruginosa in intestinally immunized rats
Authors: WILSON NR , DUNKLEY ML , BURET A , YOUNG B , CRIPPS AW 
Published: July 2007

SummaryThis paper examines the histology of rat lungs following intestinal immunization with killed mucoid Pseudomonas aerugtnosa and subsequent pulmonary challenge with live P. aeruginosa. The lungs of non‐immune challenged rats developed a confluent haemorrhagic pneumonitis with degeneration and sloughing of the mucosa of the airways; perivascular infiltration with mononuclear cells was apparent 1–2 h post‐challenge; some neutrophils were present by 2 h post‐challenge; by 12h post‐challenge oedema and intra‐alveolar haemorrhage were prominent and Gram‐negative organisms were seen in large quantities. In contrast, immunized challenged animals showed a pronounced neutrophilic response 1–2 h post‐challenge; by 12 h post‐challenge patchy abscesses were apparent with resolving inflammation and no organisms visible. The findings suggest that intestinal immunization prevents the development of fatal P. aeruginosa infections in the lung by accelerating the recruitment of polymorphonuclear neutrophils
cDNA cloning of porcine granulocyte‐macrophage colony‐stimulating factor
Authors: INUMARU S , TAKAMATSU H 
Published: July 2007

SummaryPorcine granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) cDNA was cloned by using polymerase chain reaction (PCR) and sequenced. A coding sequence of the porcine GM‐CSF precursor protein, including the signal peptide sequence and stop codon, is 435 bp in length. The identities of the porcine GM‐CSF coding sequence when compared to ovine, bovine, human and murine sequences were 89, 86, 83 and 70% at the nucleotide level, and 80, 74, 73 and 56% at the amino acid level. The hydrophobicity profiles, putative glycosylation sites and positions of cysteine residues were highly conserved in porcine, ovine, bovine and human GM‐CSF but not murine. This is the first report of the porcine GM‐CSF cDNA cloning and sequence.
The ecology and pathology of Epstein‐Barr virus
Authors: SCHMIDT CHRISTOPHER W , MISKO IHOR S 
Published: July 2007

SummaryEpstein‐Barr virus achieves its ubiquitous and uniform epidemiological distribution by a dual strategy of latency to guarantee lifelong persistence and intermittent replication to guarantee transmission. These two functions appear to dictate residence in different cell types: latency in B lymphocytes and replication in epithelial cells. Both of these cell compartments are potential sites for FBV‐associated malignancies.
Receptors for fibroblast growth factors
Authors: COUTTS JACQUELINE C , GALLAGHER JOHN T 
Published: July 2007

SummaryThe recent discovery of the involvement of heparan sulfate proteoglycans (HSPG) in the activation of fibroblast growth factor receptors (FGFR) has led to an intensification of study of this field. It appears that the HSPG act as low affinity receptors to which the fibroblast growth factors (FGF) must bind in order to successfully activate the high affinity FGFR. Heparan sulfate chains consisting of alternately arranged N‐acetylated or N‐sulfated glucosamine and uronic acid disaccharide regions, covalently attached to a core protein are found in two major families of cell surface HSPG, the syndecans and glypicans. A high affinity bFGF binding region has been isolated from fibroblast HS. There are four basic members of the FGFR family (FGFR 1–4), as well as a wealth of splice variants. The alternative forms of the basic receptors can have altered ligand binding or signalling qualities, depending on the region of the gene which is spliced. Investigations with null FGFR, incapable of signalling, have demonstrated the requirement for FGF in the organization of mammalian tissues and in embryonic patterning. Mutation of the FGFR genes has been recognized recently in human craniosynostoses where a single base pair mutation in the FGFR gene results in skeletal malformations specific to each syndrome. One suggestion is that the interaction of the mutant FGFR with the HSPG/FGF complex somehow contributes to the disease phenotype.
THE DISTRIBUTION AND RETURN OF SOCIAL CAPITAL: EVIDENCE FROM SWEDEN
Authors: Behtoui Alireza 
Published: July 2007

ABSTRACT
This paper studies the role of social capital in the status attainment process and examines the link between the hiring process and the potential pool of social capital embedded in a person's network. The analysis is based on a sample of people newly employed by the municipal services in Malmö, the third largest city in Sweden. Jobs in this sector of labour market are mainly low-paid, and are dominated by women and immigrants. The position generator method is used to measure social capital, understood as assets captured by individuals in social networks. The findings demonstrate that access to social capital is positively related to work experience, a higher educational level, having a partner, and active membership of voluntary associations. It is also apparent that being an immigrant is associated with a substantial social capital deficit. Regarding the return on capital, the results show that both human capital and social capital were rewarded with higher wages and more adequate jobs. Furthermore, we found that social capital is associated with better labour market outcomes, whether or not respondents reported that they obtained their current jobs using informal job-search methods. Results also show similar returns on access to social capital for natives and immigrants.
LEARNING FROM OTHERS AND RECEIVING SUPPORT: THE IMPACT OF PERSONAL NETWORKS ON FERTILITY INTENTIONS IN POLAND
Authors: Bühler Christoph , Fratczak Ewa 
Published: July 2007

ABSTRACT
Research about fertility has focused in the main on studying separately the influence of communication networks and social capital on reproductive behavior, but it has rarely tried to integrate both network properties theoretically or analytically. We therefore discuss a general model of purposeful behavior that perceives individuals’ subjective perceptions of the utilities of different courses of action to be affected by structures of interpersonal influence. Resources needed to realize desired goals are furthermore shaped by exchange relationships that build social capital. These considerations are empirically applied to explanations of the intentions of 758 Polish men and women ever to have a first, second, or third child. Personal networks are especially relevant for the considerations to have a first or second child. The intentions of childless respondents are positively influenced by network partners who are at a similar stage of their reproductive biographies or who have already taken the step of having a first child. However, respondents with one child have a higher probability of intending to have a second child the more they have access to fertility-related social capital.
SPEEDING UP OR HOLDING BACK?: INSTITUTIONAL FACTORS IN THE DEVELOPMENT OF CHILDCARE PROVISION IN SPAIN
Authors: León Margarita 
Published: July 2007

ABSTRACT
This paper looks at childcare provision in Spain from the perspective of policies for the reconciliation of work and family life. The goal is to understand how social care – and childcare in particular – has been placed within the different policy domains of the welfare state, and how this condition affects its opportunities for policy development and innovation. As a point of reference, the study takes into consideration the recent EU benchmark regarding childcare provision in the context of the European Employment Strategy. The investigation looks at the impact of the institutional configuration of the welfare system and the labour market on the development of childcare provision and policies for the reconciliation of work and family. The paper suggests that, given a strong policy legacy in family policy and social services, childcare provision is expanding under the decentralized education system although it has not been articulated in terms of policies for the reconciliation of work and family life, which impacts on female employment. Legislative changes improving the conditions of female employees who give birth have recently been introduced in labour law, although the structure of the labour market and practices in employment relations pose obstacles to their effective implementation.
THE EUROPEAN SOCIO-ECONOMIC CLASSIFICATION: A NEW SOCIAL CLASS SCHEMA FOR COMPARATIVE EUROPEAN RESEARCH
Authors: Rose David , Harrison Eric 
Published: July 2007

ABSTRACT
As a result of an initiative by the European Statistical Office as part of its Statistical Harmonisation Programme, a prototype of a common European Socio-economic Classification (ESeC) has been created. ESeC is a categorical social class schema based on the concept of employment relations. The paper explains the conceptual basis of ESeC, describes the categories of the classification and how they may be collapsed for analytic purposes, as well as indicating how it is operationalised. The operational variants of ESeC, depending on the data available for its construction, are also discussed. In the second part of the paper some key findings of comparative analyses which use ESeC to examine issues relating to unemployment, education, poverty, deprivation and health across the EU are summarised. These analyses demonstrate the potential of ESeC as a major advance for an improved understanding of the patterns of European social inequalities. As such, this new classification should be of vital importance to both academic and policy researchers.
Molecular cloning of Brassica rapa nitrilases and their expression during clubroot development
Authors: ISHIKAWA TOSHIKI , OKAZAKI KEIICHI , KURODA HARUKA , ITOH KIMIKO , MITSUI TOSHIAKI , HORI HIDETAKA 
Published: July 2007

SUMMARYThree isoforms of nitrilase were cloned from turnip, Brassica rapa L., and their expression during clubroot development caused by Plasmodiophora brassicae was investigated. The isoforms were designated BrNIT‐T1, BrNIT‐T2 and BrNIT‐T4 based on homology to known nitrilases. BrNIT‐T1 and BrNIT‐T2 have 80% homology to three nitrilases from Arabidopsis thaliana (AtNIT1, AtNIT2 and AtNIT3). BrNIT‐T4 showed 90% homology to AtNIT4. To confirm their enzyme activity, the recombinant proteins were expressed in Escherichia coli. The recombinant BrNIT‐T1 and BrNIT‐T2 but not BrNIT‐T4 converted indole‐3‐acetonitrile to indole‐3‐acetic acid, an endogenous plant auxin, although kinetic analysis showed that indole‐3‐acetonitrile is a poor substrate compared with various aliphatic and aromatic nitriles. By contrast, the recombinant BrNIT‐T4 specifically converted β‐cyano‐l‐alanine to aspartic acid and asparagine and these findings agree with the idea that it is involved in the cyanide detoxification pathway. Real‐time PCR analysis clearly showed that these isoforms were differentially expressed during clubroot development. BrNIT‐T1 transcripts were very low in non‐infected roots but were enhanced up to 100‐fold in infected roots exhibiting club growth. By contrast, BrNIT‐T2 transcripts remained at a very low level during clubroot formation. All these results clearly indicate the specific involvement of BrNIT‐T1 in clubroot formation. The BrNIT‐T4 transcripts were substantially reduced in the clubroot‐growing phase, but thereafter they increased rapidly to a level found in non‐infected roots as the clubroot growth reached a plateau. These findings suggest the specific involvement of BrNIT‐T4 in clubroot maturation. In fully developed clubs, the BrNIT‐T1 and BrNIT‐T2 transcripts also increased. Free indole‐3‐acetic acid (IAA) content increased in the early and the latest phase of infected roots compared with non‐infected roots, but decreased substantially at the middle phase. Thus, free IAA may play a role in the initiation and maturation of clubroot. Total IAA content was significantly higher in infected roots than in non‐infected roots throughout clubroot development and IAA conjugation/conjugate hydrolysis system as well as BrNIT‐Ts appear to be involved in clubroot development.
Bortezomib in combination with intermediate‐dose dexamethasone and continuous low‐dose oral cyclophosphamide for relapsed multiple myeloma
Authors: Kropff Martin , Bisping Guido , Schuck Elke , Liebisch Peter , Lang Nicola , Hentrich Markus , Dechow Tobias , Kröger Nicolaus , Salwender Hans , Metzner Bernd , Sezer Orhan , Engelhardt Monika , Wolf Hans‐Heinrich , Einsele Hermann , Volpert Sarah , Heinecke Achim , Berdel Wolfgang E. , Kienast Joachim ,   on behalf of the Deutsche Studiengruppe Multiples Myelom, DSMM
Published: July 2007

SummaryA phase 2 trial was performed to study the combination of bortezomib (VELCADE®) with intermediate‐dose dexamethasone (DEX), and continuous low‐dose oral cyclophosphamide (CY) in patients with relapsed multiple myeloma (MM). Fifty‐four patients with advanced MM were enroled to receive eight 3‐week treatment cycles with bortezomib 1·3 mg/m2 on days 1, 4, 8, and 11, followed by three 5‐week cycles with bortezomib 1·3 mg/m2 on days 1, 8, 15, and 22. Within all cycles, DEX 20 mg/d was given orally on the day of bortezomib injection and the day thereafter. In addition, patients received CY continuous oral treatment at a dose of 50 mg/d p.o. once daily. Fifty patients completing at least one treatment cycle were evaluable for response. Complete, partial, and minor responses occurred in 16%, 66% and 8% of patients, respectively; overall response rate 90% (efficacy analysis). Median event‐free survival was 12 months, with a median overall survival of 22 months. Adverse events (AE) of grades 3 or 4 occurring in at least 10% of patients comprised leucopenia, infection, herpes zoster, thrombocytopenia, neuropathy and fatigue. Bortezomib combined with DEX and CY is a highly effective treatment for relapsed MM at an acceptable rate of grade 3/4 AE. Antiviral prophylaxis appears to be mandatory.
Activation of Wnt/β‐catenin pathway mediates growth and survival in B‐cell progenitor acute lymphoblastic leukaemia
Authors: Khan Naveed I. , Bradstock Kenneth F. , Bendall Linda J. 
Published: July 2007

SummaryThis study investigated the response of acute lymphoblastic leukaemia (ALL) cells to Wnt proteins. Accumulation of β‐catenin was measured by Western blotting and immunofluorescence microscopy. Reverse transcription polymerase chain reaction (RT‐PCR) analysis of B‐cell progenitor acute lymphoblastic leukaemia (ALL) cells revealed expression of Wnt genes, including WNT2B in 33%, WNT5A in 42%, WNT10B in 58% and WNT16B in 25% of cases. The Wnt receptors, (Frizzled) FZD7 and FZD8 were also expressed in most cases while FZD3, FZD4 and FZD9 were occasionally detected. Stimulation of ALL cells with Wnt‐3a activated canonical Wnt signalling with increased expression and nuclear translocation of β‐catenin. This resulted in a 1·7‐ to 5·3‐fold increase in cell proliferation, which was associated with enhanced cell cycle entry. A significant increase in the survival of ALL cells under conditions of serum deprivation was also observed. Microarray analysis and quantitative RT‐PCR revealed that activation of the Wnt/β‐catenin pathway led to altered expression of genes involved in cell cycle regulation and apoptosis in normal and leukaemic B‐cell progenitors. Our results demonstrate that Wnt‐3a provides proliferative and survival cues in ALL cells. This data suggests that targeting the Wnt signalling pathway may be a useful therapeutic strategy in ALL.