bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic bronchitis and urban air pollution in an international study
Authors: Sunyer J , Jarvis D , Gotschi T , Garcia-Esteban R , Jacquemin B , Aguilera I , Ackerman U , de Marco R , Forsberg B , Gislason T , Heinrich J , Norbäck D , Villani S , Künzli N 
Published: July 2006

Objectives:The chronic effects of urban air pollution are not well known. The authors’ aim was to investigate the association between the prevalence and new onset of chronic bronchitis and urban air pollution.Methods:Subjects from the general population randomly selected for the European Community Respiratory Health Survey (ECRHS I) during 1991–93 in 21 centres in 10 countries were followed up from the years 2000 to 2002 (n = 3232 males and 3592 females; average response rate = 65.3%). PM2.5and elements, with the same equipment at centre level, and home outdoor NO2in 1634 individuals were measured. Hierarchical models were used.Results:The prevalence and new onset of chronic phlegm during follow up were 6.9% and 4.5%, respectively, 5.3% in males and 3.5% in females. Smoking, rhinitis, poor education, and low social class were associated with (prevalence and new onset of) chronic phlegm in both genders, and occupational exposures in males and traffic intensity (adjusted odds ratio for constant traffic, OR = 1.86; 95% CI 1.24 to 2.77) as well as home outdoor NO2(OR > 50 μg/m3v< 20μg3 =  2.71; 95% CI 1.03 to 7.16) among females. PM2.5and S content at centre level did not show any association with prevalence or new onset of chronic phlegm. Similar results were obtained with chronic productive cough.Conclusion:Individual markers of traffic at household level such as reported intensity and outdoor NO2were risk factors for chronic bronchitis among females.
Inhibitors in mild/moderate haemophilia A: An update
Authors: Salvagno Gian , Lippi Giuseppe , Franchini Massimo 
Published: July 2006

SummaryThe development of inhibitors in patients with mild/moderate hemophilia A is an increasingly recognized occurrence and is manifested by the patients’ bleeding pattern becoming more severe. Inherited (hemophilia genetic mutations) and acquired (type and delivery of factor VIII replacement therapy) factors have been associated with an increased likelihood of developing factor VIII inhibitors. Although the use of bypassing agents (i.e. activated prothrombin complex concentrates and recombinant factor VII activated) has been demonstrated to be effective in controlling bleeding episodes in patients who develop factor VIII inhibitors, the limited data available in the literature are insufficient to determine the optimal approach to the eradication of inhibitors (i.e. immune tolerance induction, immunosuppression or both) for this group. Particular attention should be directed to the prevention of this complication in those patients with mild/moderate hemophilia recognized to be at increased risk of developing a factor VIII inhibitor. In conclusion, large prospective trials are warranted in order to elucidate the many still unclear pathogenic and therapeutic aspects of the development of inhibitors in patients with mild/moderate hemophilia A.
Association of homocysteine (but not of MTHFR 677 C>T, MTR 2756 A>G, MTRR 66 A>G and TCN2 776 C>G) with ischaemic cerebrovascular disease in Sicily
Authors: Guéant-Rodriguez Rosa-Maria , Anello Guido , Spada Rosario , Romano Antonino , Fajardo Adrian , Caraci Filippo , Ferri Raffaele , Guéant Jean-Louis , Bosco Paolo 
Published: July 2006

SummaryAssociation between methylenetetrahydrofolate reductase polymorphism (MTHFR 677 C>T), a determinant of homocysteine plasma level (t-Hcys), with ischaemc cerebrovascular disease (iCVD) seems to be neutral in North Europe and North America. The association of 2756 A>G of methionine synthase (MTR), 66 A>G of methionine synthase reductase (MTRR) and 776 C>G of transcobalamin (TCN2) needs to be evaluated further. It was the objective of this study to evaluate the association of these polymorphisms, t-Hcys, vitamin B12 and folate levels with iCVD, in an Italian population from Sicily. We investigated the association of these polymorphisms, t-Hcys, vitamin B12 and folate with iCVD in 252 subjects, including 131 cases and 121 sexand agematched healthy controls. t-Hcys was higher in the iCVD group than in controls [15.3 (11.5–17.9) vs. 11.6 (9.4–14.5) µM; P=0. 0007] and also in subjects withTCN2 776CG genotype, compared to homozygous genotypes [13.5 (9.9± 16.9) vs. 11.7 (9.6 ± 14.4) µM; P=0. 0327]. The folate level in cases and controls was consistent with an adequate dietary intake [12.7 (9.0–15.3) vs. 12.5 (9.6–16.9) nM; P=0. 7203]. In multivariate analysis, t-Hcys was a significant independent predictor of iCVD with an odds ratio of 1.14 (95% C.I. : 1.06–1.24; P=0. 0006). No association was found between MTHFR, MTR, MTRR and TCN2 polymorphisms and iCVD risk. We have found an influence of t-Hcys and a neutral effect of MTHFR, MTR, MTRR and TCN2 on iCVD risk in Sicily. The neutral influence of these polymorphisms may be explained by adequate status in folate and vitamin B12. Other factors underlying the increased t-Hcys need further investigations.
Long-term stability of relationships between reference materials for thromboplastins
Authors: van den Besselaar Anton M. H. P. , Tripodi Armando , Linsinger Thomas P. J. 
Published: July 2006

SummaryReference materials for thromboplastins are available from the World Health Organization (WHO) and the European Commission (EC). The long-term stability of the reference materials is an essential requirement and must be monitored. The relationship between two reference materials for rabbit thromboplastin, i. e. ERM-AD149 (EC) and RBT/90 (WHO), has been monitored in the period 1996–2002. No significant trend with time was detected. In addition,the relationship between ERM-AD149 and the reference material for bovine thromboplastin (i. e. OBT/79) has been determined in 1994 and in 2005 in multicentre studies (n = 11 and n = 9, respectively). No significant changes were observed in the relationships between these reference materials when all results were included (5% significance level).
Antiadhesive effect of fibrinogen: a safeguard for thrombus stability
Authors: Lishko Valeryi K. , Burke Timothy , Ugarova Tatiana 
Published: July 2006

AbstractThe recruitment of phagocytic leukocytes to sites of vessel wall injury plays an important role in thrombus dissolution by proteases elaborated on their adhesion. However, leukocyte adhesion to the fibrin clot can be detrimental at the early stages of wound healing when hemostatic plug integrity is critical for preventing blood loss. Adhesion of circulating leukocytes to the insoluble fibrin(ogen) matrix is mediated by integrins and occurs in the presence of a high concentration of plasma fibrinogen. In this study, the possibility that soluble fibrinogen could protect fibrin from excessive adhesion of leukocytes was examined. Fibrinogen was a potent inhibitor of adhesion of U937 monocytoid cells and neutrophils to fibrin gel and immobilized fibrin(ogen). An investigation of the mechanism by which soluble fibrinogen exerts its influence on leukocyte adhesion indicated that it did not block integrins but rather associated with the fibrin(ogen) substrate. Consequently, leukocytes that engage fibrinogen molecules loosely bound to the surface of fibrin(ogen) matrix are not able to consolidate their grip on the substrate; subsequently, cells detach. This conclusion is based on the evidence obtained in adhesion studies using various cells and performed under static and flow conditions. These findings reveal a new role of fibrinogen in integrin-mediated leukocyte adhesion and suggest that this mechanism may protect the thrombus from premature dissolution.
The Hlx homeobox transcription factor is required early in enteric nervous system development
Authors: Bates Michael D , Dunagan Dana T , Welch Lynn C , Kaul Ajay , Harvey Richard P 
Published: July 2006

Abstract
Background
Development of the enteric nervous system (ENS) requires interactions between migrating neural crest cells and the nascent gastrointestinal tract that are dependent upon genes expressed by both cell compartments. Hlx, a homeobox transcription factor gene that is expressed in mouse intestinal and hepatic mesenchyme, is required for normal embryonic growth of intestine and liver, and the Hlx-/- genotype is embryonic lethal. We hypothesized that Hlx is required for ENS development.

Results
Enteric neurons were identified in Hlx+/+ and Hlx-/- mouse embryos by immunostaining of embryo sections for the neural markers PGP9.5 and Phox2b, or by staining for β-galactosidase in whole-mount embryos containing the dopamine β-hydroxylase-nLacZ transgene. In Hlx+/+ embryos, neural crest cells/enteric neurons have moved from the stomach into the intestine by E10.5. By contrast, neural crest cells/enteric neurons remain largely restricted to the lateral stomach mesenchyme of Hlx-/- embryos, with only a few scattered neural crest cells/enteric neurons in the intestine between E10.5–16.5.

Conclusion
The Hlx homeobox transcription factor is required for early aspects of ENS development.
Extra-osseous osteochondroma-like soft tissue mass of the patello-femoral space
Authors: Oliva Francesco , Marconi Alessandro , Fratoni Stefano , Maffulli Nicola 
Published: July 2006

AbstractBackgroundExtraskeletal cartilaginous tumors are uncommon. Osteochondromas usually arise from the metaphyseal region of the growing skeleton.Case presentationA 53 year old man presented with a three years history of anterior knee pain and inability to flex his knee more than 90°. Clinical examination and imaging studies revealed a nodular calcific mass in the anterior portion of the knee, displacing the medial portion of the patellar tendon. Following excision, histopathology confirmed the diagnosis of extra-osseous osteochondroma-like soft tissue mass, with no recurrence 24 months after surgery.ConclusionAn integrated clinical-pathologic diagnosis helps to clarify the nature of extraskeletal cartilaginous tumors that can arise at unusual anatomic site. Complete local surgical excision is the management of choice.
The contribution of qualitative research in designing a complex intervention for secondary prevention of coronary heart disease in two different healthcare systems
Authors: Corrrigan Mairead , Cupples Margaret E , Smith Susan M , Byrne Molly , Leathem Claire S , Clerkin Pauline , Murphy Andrew W 
Published: July 2006

Abstract
Background
Developing complex interventions for testing in randomised controlled trials is of increasing importance in healthcare planning. There is a need for careful design of interventions for secondary prevention of coronary heart disease (CHD). It has been suggested that integrating qualitative research in the development of a complex intervention may contribute to optimising its design but there is limited evidence of this in practice. This study aims to examine the contribution of qualitative research in developing a complex intervention to improve the provision and uptake of secondary prevention of CHD within primary care in two different healthcare systems.

Methods
In four general practices, one rural and one urban, in Northern Ireland and the Republic of Ireland, patients with CHD were purposively selected. Four focus groups with patients (N = 23) and four with staff (N = 29) informed the development of the intervention by exploring how it could be tailored and integrated with current secondary prevention activities for CHD in the two healthcare settings. Following an exploratory trial the acceptability and feasibility of the intervention were discussed in four focus groups (17 patients) and 10 interviews (staff). The data were analysed using thematic analysis.

Results
Integrating qualitative research into the development of the intervention provided depth of information about the varying impact, between the two healthcare systems, of different funding and administrative arrangements, on their provision of secondary prevention and identified similar barriers of time constraints, training needs and poor patient motivation. The findings also highlighted the importance to patients of stress management, the need for which had been underestimated by the researchers. The qualitative evaluation provided depth of detail not found in evaluation questionnaires. It highlighted how the intervention needed to be more practical by minimising administration, integrating role plays into behaviour change training, providing more practical information about stress management and removing self-monitoring of lifestyle change.

Conclusion
Qualitative research is integral to developing the design detail of a complex intervention and tailoring its components to address individuals' needs in different healthcare systems. The findings highlight how qualitative research may be a valuable component of the preparation for complex interventions and their evaluation.
Inhibition of HIV-1 replication by RNA interference of p53 expression
Authors: Pauls Eduardo , Senserrich Jordi , Clotet Bonaventura , Esté Jose A 
Published: July 2006

Abstract
p53 expression and activation have been associated to faster human immunodeficiency virus (HIV) disease progression, most probably by inducing CD4+ T cell death but also through its cooperative effect in the control of viral gene transcription by viral regulatory proteins. Here, we show that RNA interference of p53 in HIV-1 reporter (HeLa P4-R5 MAGI) and lymphoid (SupT1) cell lines blocked HIV-1 and Tat-induced transcription from the HIV-1 promoter and HIV-1 replication in acutely infected cells, suggesting a cooperative role of p53 in HIV-1 transcription. Contrary to SupT1 cells, which encoe several mutations on the p53 DNA binding domain, death of HIV-1-induced syncytia was reduced in cocultures of HeLa P4-R5 MAGI with persistently infected HIV-1 cells. To our knowledge, this is the first demonstration of the effect of the loss of function of p53 in HIV-1 replication, which is independent on its classical DNA binding activity. Our results suggest two independent roles for p53 in HIV-1 infection: cooperation in HIV long-terminal repeat transcription and virus-induced cell death.
The dermal microenvironment induces the expression of the alternative activation marker CD301/mMGL in mononuclear phagocytes, independent of IL-4/IL-13 signaling
Authors: Dupasquier Marcel , Stoitzner Patrizia , Wan Hui , Cerqueira Denise , Van Oudenaren Adri , Voerman Jane S A , Denda-Nagai Kaori , Irimura Tatsuro , Raes Geert , Romani Nikolaus , Leenen Pieter J M 
Published: July 2006

Abstract
Recently, we have shown that mononuclear phagocytes comprise the majority of interstitial cells in the mouse dermis, as indicated by their phenotypic and functional characteristics. In particular, these cells express the mouse macrophage galactose-/N-acetylgalactosamine-specificlectin (mMGL)/CD301, identified by the monoclonal antibody ER-MP23, as well as other macrophage markers. As expression of mMGL is induced by IL-4 or IL-13 and is therefore a marker of alternatively activated macrophages, we asked whether dermal mononuclear phagocytes are genuinely alternatively activated. We observed that these cells expressed, next to mMGL, two other alternative activation markers, namely, the mannose receptor/CD206 and Dectin-1. Yet, as this expression profile was similar in IL-4 receptor α knockout mice, neither IL-4 nor IL-13 signaling appeared to be required for this phenotype. We also found that Langerhans cells (LC), which showed only a low level of mMGL in the epidermis, up-regulated mMGL expression upon migration through the dermis, allowing these cells to internalize limited amounts of mMGL ligands. LC isolated from epidermal preparations did not show this up-regulation when cultured in standard medium, but whole skin-conditioned medium did stimulate mMGL expression by LC. The vast majority of mMGL molecules was present in the cytoplasm, however. LC, which arrived in skin-draining lymph nodes, quickly down-regulated mMGL expression, and dermally derived cells retained significant mMGL levels. Taken together, these data suggest that the dermal microenvironment induces mononuclear phagocyte subpopulations to express mMGL and possibly other markers of alternatively activated macrophages, independent of IL-4/IL-13 signaling.
The C-terminal flavin domain of gp91phox bound to plasma membranes of granulocyte-like X-CGD PLB-985 cells is sufficient to anchor cytosolic oxidase components and support NADPH oxidase-associated diaphorase activity independent of cytosolic phospholipase A2 regulation
Authors: Pessach Itai , Shmelzer Zeev , Leto Thomas L , Dinauer Mary C , Levy Rachel 
Published: July 2006

Abstract
We have previously established a model of cytosolic phospholipase A2 (cPLA2)-deficient PLB-985 cells and demonstrated that cPLA2-generated arachidonic acid (AA) is essential for reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation and NADPH-dependent diaphorase activity. The present study focuses on the C-terminal cytoplasmic domain of gp91phox (residues 283–570), which contains the NADPH binding and flavin adenine dinucleotide-reducing center, to determine if this portion is regulated by AA. The gp91phox C-terminal reductase domain was expressed in X-CGD PLB-985 cells lacking normal gp91phox (X-CGD PLB 91CT cells) and was detected in the plasma membrane. It appears to be bound electrostatically to the plasma membrane, as it is eluted by high salt. Permeabilized, granulocyte-like X-CGD PLB 91CT cells lacking cPLA2 protein and activity, as well as AA release after stimulation, supported NADPH-dependent diaphorase activity after stimulation, similar to granulocyte-like X-CGD PLB 91CT cells. Normal translocation of p47phox and p67phox to the membrane fractions of both stimulated cell types indicated that the gp91phox C-terminal region is sufficient to anchor the cytosolic oxidase components to the membranes. cPLA2 translocated to membranes and bound the assembled oxidase in granulocyte-like X-CGD PLB 91CT cells after stimulation. Therefore, the assembled membrane-bound oxidase complex encompassing the flavin domain of gp91phox provides a docking site for cPLA2 but is not the site of AA-based regulation of oxidase activity.
IP3Rs are sufficient for dendritic cell Ca2+ signaling in the absence of RyR1
Authors: Stolk Meaghan , Leon-Ponte Matilde , Merrill Mia , Ahern Gerard P , O’Connell Peta J 
Published: July 2006

Abstract
Calcium (Ca2+) signaling plays a pivotal role in the function of dendritic cells (DC). The Type 1 ryanodine receptor (RyR), a major intracellular Ca2+ channel, is highly expressed in immature DC. We therefore investigated whether RyR1 plays a role in DC development and function by studying properties of DC derived from wild-type (WT) and RyR1 null [knockout (KO)] mice. Fetal liver cells from WT and RyR1 KO mice retained full hematopoietic competence. Adoptive transfer of these cells into congenic hosts resulted in the generation of functionally equivalent DC populations. WT and RyR1 KO DC exhibited a similar capacity to mature in response to inflammatory and/or activation stimuli, to endocytose antigen, and to stimulate T cell proliferation. Moreover, the absence of RyR1 did not lead to de novo expression of RyR2 or RyR3. WT and RyR KO DC express all three isoforms of inositol 1,4,5-trisphosphate receptor (IP3R), although Type 3 IP3R gene transcripts are predominant. Further, IP3-mediated Ca2+ transients proceed normally after inhibition of RyRs with dantrolene. Signaling via IP3R may therefore be sufficient to drive essential DC Ca2+ signaling processes in the absence of RyR expression or function.
Terminal B cell differentiation is skewed by deregulated interleukin-6 secretion in β2 integrin-deficient mice
Authors: Peters Thorsten , Bloch Wilhelm , Wickenhauser Claudia , Tawadros Samir , Oreshkova Tsvetelina , Kess Daniel , Krieg Thomas , Müller Werner , Scharffetter-Kochanek Karin 
Published: July 2006

Abstract
Absence of the common β chain (CD18) of β2 integrins leads to leukocyte-adhesion deficiency type-1 (LAD1) in humans. Mice with a CD18 null mutation suffer from recurrent bacterial infections, impaired wound healing, and skin ulcers, closely resembling human LAD1. Previous findings in CD18−/− mice demonstrated a skewed terminal B cell differentiation with plasmacytosis and elevated serum immunoglobulin G (IgG). As interleukin-6 (IL-6) is a potent enhancer of plasma cell formation and Ig secretion, we assessed IL-6 serum levels of CD18−/− and wild-type (WT) mice kept under a conventional or barrier facility or specific pathogen-free (SPF) conditions. We detected an up to 20-fold increase in IL-6 in serum of CD18−/− mice compared with WT controls when kept under conventional or barrier facility conditions, respectively. Under SPF conditions, no significant differences in terms of IL-6 serum levels were found between CD18−/− and WT mice. However, histological alterations of secondary lymphoid tissues, plasmacytosis, abnormal plasmacytoid cells (Mott cells), and hypergammaglobulinemia persisted. To further analyze the role of IL-6 in these pathological alterations, we established a CD18−/− IL-6−/− double-deficient mouse mutant. In these mice, serum IgG levels were normal, and the altered plasma cell phenotype, including Mott cells, was no longer detectable. The CD18−/− IL-6−/− double-deficient mouse model thus demonstrated that IL-6 is responsible for parts of the phenotype seen in the CD18−/− mouse mutants. It may be of interest to examine human leukocyte-adhesion deficiency type-1 patients closer and search for pathological changes possibly induced via overproduction of IL-6.
An Orally Administered Multitarget Tyrosine Kinase Inhibitor, SU11248, Is a Novel Potent Inhibitor of Thyroid Oncogenic RET/Papillary Thyroid Cancer Kinases
Authors: Kim Dong Wook , Jo Young Suk , Jung Hye Sook , Chung Hyo Kyun , Song Jung Hun , Park Ki Cheol , Park Su Hyeon , Hwang Jung Hwan , Rha So Young , Kweon Gi Ryang , Lee Su-Jae , Jo Ki-Won , Shong Minho 
Published: July 2006

Abstract
Context: The oncogenic RET/PTC tyrosine kinase causes papillary thyroid cancer (PTC). The use of inhibitors specific for RET/PTC may be useful for targeted therapy of PTC.
Objective: The objective of the study was to evaluate the efficacies of the recently developed kinase inhibitors SU11248, SU5416, and SU6668 in inhibition of RET/PTC.
Design: SU11248, SU5416, and SU6668 were synthesized, and their inhibitory potencies were evaluated using an in vitro RET/PTC kinase assay. The inhibitory effects of the compounds on RET/PTC were evaluated by quantifying the autophosphorylation of RET/PTC, signal transducer and activator of transcription (STAT)-3 activation, and the morphological reversal of RET/PTC-transformed cells.
Results: An in vitro kinase assay revealed that SU5416, SU6668, and SU11248 inhibited phosphorylation of the synthetic tyrosine kinase substrate peptide E4Y by RET/PTC3 in a dose-dependent manner with IC50 of approximately 944 nm for SU5416, 562 nm for SU6668, and 224 nm for SU11248. Thus, SU11248 effectively inhibits the kinase activity of RET/PTC3. RET/PTC-mediated Y705 phosphorylation of STAT3 was inhibited by addition of SU11248, and the inhibitory effects of SU11248 on the tyrosine phosphorylation and transcriptional activation of STAT3 were very closely correlated with decreased autophosphorylation of RET/PTC. SU11248 caused a complete morphological reversion of transformed NIH-RET/PTC3 cells and inhibited the growth of TPC-1 cells that have an endogenous RET/PTC1.
Conclusion: SU11248 is a highly effective tyrosine kinase inhibitor of the RET/PTC oncogenic kinase.