bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacists' perceptions of their practice: a comparison between Alberta and Northern Ireland
Authors: Al Hamarneh Yazid N , Rosenthal Meagen , McElnay James C , Tsuyuki Ross T 
Published: September 2011

Abstract

Objective
To explore how community pharmacists from Alberta, Canada, and Northern Ireland, UK, describe what a pharmacist does and to compare their responses.

Methods
Two hundred community pharmacists were interviewed using the telephone. The interviewer who introduced himself as a researcher asked two questions about the period over which the participants had been practising pharmacy and the way they describe what a pharmacist does. Responses were categorised into three categories: patient-centred, product-focused and ambiguous. Word-cloud analysis was used to assess the use of patient-care-related terms.

Key findings
Of the responses from community pharmacists in Alberta, 29% were categorised as patient-centred, 45% as product-focused and 26% as ambiguous. In Northern Ireland, 40% of the community pharmacists' responses were categorised as patient-centred, 39% as product-focused and 21% as ambiguous. Community pharmacists in Northern Ireland provided more patient-centred responses than community pharmacists in Alberta (P = 0.013). The word-cloud analysis showed that ‘medicine’ and ‘dispense’ were the most frequently reported terms. It also highlighted a relative lack of patient-care-related terms.

Conclusions
The findings of the present study are suggestive of some movement towards patient-centredness; however, product-focused practice still predominates within the pharmacy profession in Alberta and Northern Ireland. The relative lack of patient-care-related terms suggests that patient care is still not the first priority for pharmacists in both Alberta and Northern Ireland.
Surface-Affinity Profiling To Identify Host-Pathogen Interactions
Authors: Boleij Annemarie , Laarakkers Coby M. , Gloerich Jolein , Swinkels Dorine W. , Tjalsma Harold 
Published: September 2011

ABSTRACT

Proteolytic treatment of intact bacterial cells has proven to be a convenient approach for the identification of surface-exposed proteins. This class of proteins directly interacts with the outside world, for instance, during adherence to human epithelial cells. Here, we aimed to identify host receptor proteins by introducing a preincubation step in which bacterial cells were first allowed to capture human proteins from epithelial cell lysates. Using
Streptococcus gallolyticus
as a model bacterium, liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of proteolytically released peptides yielded the identification of a selective number of human epithelial proteins that were retained by the bacterial surface. Of these potential receptors for bacterial interference, (cyto)keratin-8 (CK8) was verified as the most significant hit, and its surface localization was investigated by subcellular fractionation and confocal microscopy. Interestingly, bacterial enolase could be assigned as an interaction partner of CK8 by MS/MS analysis of cross-linked protein complexes and complementary immunoblotting experiments. As surface-exposed enolase has a proposed role in epithelial adherence of several Gram-positive pathogens, its interaction with CK8 seems to point toward a more general virulence mechanism. In conclusion, our study shows that surface-affinity profiling is a valuable tool to identify novel adhesin-receptor pairs, which advocates its application in other hybrid biological systems.
Toll-Like Receptor 9 Modulates Macrophage Antifungal Effector Function during Innate Recognition of Candida albicans and Saccharomyces cerevisiae
Authors: Kasperkovitz Pia V. , Khan Nida S. , Tam Jenny M. , Mansour Michael K. , Davids Peter J. , Vyas Jatin M. 
Published: September 2011

ABSTRACT

Phagocytic responses are critical for effective host defense against opportunistic fungal pathogens. Macrophages sample the phagosomal content and orchestrate the innate immune response. Toll-like receptor 9 (TLR9) recognizes unmethylated CpG DNA and is activated by fungal DNA. Here we demonstrate that specific triggering of TLR9 recruitment to the macrophage phagosomal membrane is a conserved feature of fungi of distinct phylogenetic origins, including
Candida albicans
,
Saccharomyces cerevisiae
,
Malassezia furfur
, and
Cryptococcus neoformans
. The capacity to trigger phagosomal TLR9 recruitment was not affected by a loss of fungal viability or cell wall integrity. TLR9 deficiency has been linked to increased resistance to murine candidiasis and to restriction of fungal growth
in vivo
. Macrophages lacking TLR9 demonstrate a comparable capacity for phagocytosis and normal phagosomal maturation compared to wild-type macrophages. We now show that TLR9 deficiency increases macrophage tumor necrosis factor alpha (TNF-α) production in response to
C. albicans
and
S. cerevisiae
, independent of yeast viability. The increase in TNF-α production was reversible by functional complementation of the TLR9 gene, confirming that TLR9 was responsible for negative modulation of the cytokine response. Consistently, TLR9 deficiency enhanced the macrophage effector response by increasing macrophage nitric oxide production. Moreover, microbicidal activity against
C. albicans
and
S. cerevisiae
was more efficient in TLR9 knockout (TLR9KO) macrophages than in wild-type macrophages. In conclusion, our data demonstrate that TLR9 is compartmentalized selectively to fungal phagosomes and negatively modulates macrophage antifungal effector functions. Our data support a model in which orchestration of antifungal innate immunity involves a complex interplay of fungal ligand combinations, host cell machinery rearrangements, and TLR cooperation and antagonism.
Predictors of vibration perception threshold in type 2 diabetic patients with proliferative retinopathy
Authors: Magri Caroline Jane , Calleja Neville , Buhagiar Gerald , Fava Stephen , Vassallo Josanne 
Published: September 2011

ABSTRACT

Purpose of the study
Distal peripheral neuropathy (DPN) is a troublesome complication of diabetes mellitus (DM). The factors associated with the disease are still incompletely understood. The purpose of this study was to investigate factors associated with vibration perception threshold (VPT) as a marker of DPN in a type 2 diabetic population with advanced microvascular disease.

Methods
The study included 203 diabetic patients (117 male, 86 female) with proliferative diabetic retinopathy. Subjects were investigated by questionnaires, clinical examinations, blood and urine sampling, and review of medical records in the period from November 2008 through April 2009. Presence of DPN was defined as VPT ≥25 V.

Results
The mean (±SD) age was 65.2 (±9.9) years and median (IQR) diabetes duration was 18 (10–25) years. Forty-six per cent of subjects were found to have DPN, defined as a VPT ≥25 V by neurothesiometer testing. Prevalence of DPN was found to be associated with age (p=0.038), male gender (p=0.046), low haemoglobin (p&lt;0.001), high erythrocyte sedimentation rate (p=0.03), uric acid values (p=0.034), and peripheral vascular disease (PVD) (p=0.003) in univariate analysis. Multivariate logistic regression analysis revealed male gender (OR 5.52; p&lt;0.001) and low haemoglobin values (B=−0.58; p&lt;0.001) to be independent predictors of VPT ≥25 V in subjects with proliferative retinopathy, while linear regression analysis revealed male gender (p&lt;0.001), haemoglobin (p=0.001), age (p=0.04), and PVD (p=0.001) to be significant predictors of VPT.

Conclusions
This study reports a novel independent association of DPN with low haemoglobin values. In the study population with type 2 DM and proliferative retinopathy, DPN was also independently associated with male gender, age, and PVD. Further studies are needed to confirm the association with low haemoglobin and identify the underlying mechanism.
Neutrophil Degranulation and Immunosuppression in Patients with GBM: Restoration of Cellular Immune Function by Targeting Arginase I
Authors: Sippel Trisha R. , White Jason , Nag Kamalika , Tsvankin Vadim , Klaassen Marci , Kleinschmidt-DeMasters B.K. , Waziri Allen 
Published: September 2011

Abstract
Purpose: The source of glioblastoma (GBM)-associated immunosuppression remains multifactorial. We sought to clarify and therapeutically target myeloid cell–derived peripheral immunosuppression in patients with GBM.
Experimental Design: Direct ex vivo T-cell function, serum Arginase I (ArgI) levels, and circulating myeloid lineage populations were compared between patients with GBM and normal donors or patients with other intracranial tumors. Immunofunctional assays were conducted using bulk and sorted cell populations to explore the potential transfer of myeloid cell–mediated immunosuppression and to identify a potential mechanism for these effects. ArgI-mediated immunosuppression was therapeutically targeted in vitro through pharmacologic inhibition or arginine supplementation.
Results: We identified a significantly expanded population of circulating, degranulated neutrophils associated with elevated levels of serum ArgI and decreased T-cell CD3ζ expression within peripheral blood from patients with GBM. Sorted CD11b+ cells from patients with GBM were found to markedly suppress normal donor T-cell function in coculture, and media harvested from mitogen-stimulated GBM peripheral blood mononuclear cell (PBMC) or GBM-associated mixed lymphoid reactions showed ArgI levels that were significantly higher than controls. Critically, T-cell suppression in both settings could be completely reversed through pharmacologic ArgI inhibition or with arginine supplementation.
Conclusions: These data indicate that peripheral cellular immunosuppression in patients with GBM is associated with neutrophil degranulation and elevated levels of circulating ArgI, and that T-cell function can be restored in these individuals by targeting ArgI. These data identify a novel pathway of GBM-mediated suppression of cellular immunity and offer a potential therapeutic window for improving antitumor immunity in affected patients. Clin Cancer Res; 17(22); 6992–7002. ©2011 AACR.
Phase I Trial of Adoptive Cell Transfer with Mixed-Profile Type-I/Type-II Allogeneic T Cells for Metastatic Breast Cancer
Authors: Hardy Nancy M. , Mossoba Miriam E. , Steinberg Seth M. , Fellowes Vicki , Yan Xiao-Yi , Hakim Frances T. , Babb Rebecca R. , Avila Daniele , Gea-Banacloche Juan , Sportès Claude , Levine Bruce L. , June Carl H. , Khuu Hahn M. , Carpenter Ashley E. , Krumlauf Michael C. , Dwyer Andrew J. , Gress Ronald E. , Fowler Daniel H. , Bishop Michael R. 
Published: September 2011

AbstractPurpose: Metastatic breast cancer (MBC) response to allogeneic lymphocytes requires donor T-cell engraftment and is limited by graft-versus-host disease (GVHD). In mice, type-II–polarized T cells promote engraftment and modulate GVHD, whereas type-I–polarized T cells mediate more potent graft-versus-tumor (GVT) effects. This phase I translational study evaluated adoptive transfer of ex vivo costimulated type-I/type-II (T1/T2) donor T cells with T-cell–depleted (TCD) allogeneic stem cell transplantation (AlloSCT) for MBC.Experimental Design: Patients had received anthracycline, taxane, and antibody therapies, and been treated for metastatic disease and a human leukocyte antigen (HLA)-identical–sibling donor. Donor lymphocytes were costimulated ex vivo with anti-CD3/anti-CD28 antibody–coated magnetic beads in interleukin (IL)-2/IL-4–supplemented media. Patients received reduced intensity conditioning, donor stem cells and T1/T2 cells, and monitoring for toxicity, engraftment, GVHD, and tumor response; results were compared with historical controls, identically treated except for T1/T2 product infusions.Results: Mixed type-I/type-II CD4+ T cells predominated in T1/T2 products. Nine patients received T1/T2 cells at dose level 1 (5 × 106 cells/kg). T-cell donor chimerism reached 100% by a median of 28 days. Seven (78%) developed acute GVHD. At day +28, five patients had partial responses (56%) and none had MBC progression; thereafter, two patients had continued responses. Donor T-cell engraftment and tumor responses appeared faster than in historical controls, but GVHD rates were similar and responders progressed early, often following treatment of acute GVHD.Conclusion: Allogeneic T1/T2 cells were safely infused with TCD-AlloSCT, appeared to promote donor engraftment, and may have contributed to transient early tumor responses. Clin Cancer Res; 17(21); 6878–87. ©2011 AACR.
Profibrotic potential of Prominin-1+epithelial progenitor cells in pulmonary fibrosis
Authors: Blyszczuk Przemyslaw , Germano Davide , Stein Sokrates , Moch Holger , Matter Christian M , Beck-Schimmer Beatrice , Lüscher Thomas F , Eriksson Urs , Kania Gabriela 
Published: September 2011

Abstract

Background
In idiopathic pulmonary fibrosis loss of alveolar epithelium induces inflammation of the pulmonary tissue followed by accumulation of pathogenic myofibroblasts leading eventually to respiratory failures. In animal models inflammatory and resident cells have been demonstrated to contribute to pulmonary fibrosis. Regenerative potential of pulmonary and extra-pulmonary stem and progenitor cells raised the hope for successful treatment option against pulmonary fibrosis. Herein, we addressed the contribution of lung microenvironment and prominin-1+ bone marrow-derived epithelial progenitor cells in the mouse model of bleomycin-induced experimental pulmonary fibrosis.

Methods
Prominin-1+ bone marrow-derived epithelial progenitors were expanded from adult mouse lungs and differentiated in vitro by cytokines and growth factors. Pulmonary fibrosis was induced in C57Bl/6 mice by intratracheal instillation of bleomycin. Prominin-1+ progenitors were administered intratracheally at different time points after bleomycin challenge. Green fluorescence protein-expressing cells were used for cell tracking. Cell phenotypes were characterized by immunohistochemistry, flow cytometry and quantitative reverse transcription-polymerase chain reaction.

Results
Prominin-1+ cells expanded from healthy lung represent common progenitors of alveolar type II epithelial cells, myofibroblasts, and macrophages. Administration of prominin-1+ cells 2 hours after bleomycin instillation protects from pulmonary fibrosis, and some of progenitors differentiate into alveolar type II epithelial cells. In contrast, prominin-1+ cells administered at day 7 or 14 lose their protective effects and differentiate into myofibroblasts and macrophages. Bleomycin challenge enhances accumulation of bone marrow-derived prominin-1+ cells within inflamed lung. In contrast to prominin-1+ cells from healthy lung, prominin-1+ precursors isolated from inflamed organ lack regenerative properties but acquire myofibroblast and macrophage phenotypes.

Conclusion
The microenvironment of inflamed lung impairs the regenerative capacity of bone marrow-derived prominin-1+ progenitors and promotes their differentiation into pathogenic phenotypes.
Three-dimensional reconstructions of intrahepatic bile duct tubulogenesis in human liver
Authors: Vestentoft Peter S , Jelnes Peter , Hopkinson Branden M , Vainer Ben , Møllgård Kjeld , Quistorff Bjørn , Bisgaard Hanne C 
Published: September 2011

Abstract

Background
During liver development, intrahepatic bile ducts are thought to arise by a unique asymmetric mode of cholangiocyte tubulogenesis characterized by a series of remodeling stages. Moreover, in liver diseases, cells lining the Canals of Hering can proliferate and generate new hepatic tissue. The aim of this study was to develop protocols for three-dimensional visualization of protein expression, hepatic portal structures and human hepatic cholangiocyte tubulogenesis.

Results
Protocols were developed to digitally visualize portal vessel branching and protein expression of hepatic cell lineage and extracellular matrix deposition markers in three dimensions. Samples from human prenatal livers ranging from 7 weeks + 2 days to 15½ weeks post conception as well as adult normal and acetaminophen intoxicated liver were used. The markers included cytokeratins (CK) 7 and 19, the epithelial cell adhesion molecule (EpCAM), hepatocyte paraffin 1 (HepPar1), sex determining region Y (SRY)-box 9 (SOX9), laminin, nestin, and aquaporin 1 (AQP1).
Digital three-dimensional reconstructions using CK19 as a single marker protein disclosed a fine network of CK19 positive cells in the biliary tree in normal liver and in the extensive ductular reactions originating from intrahepatic bile ducts and branching into the parenchyma of the acetaminophen intoxicated liver. In the developing human liver, three-dimensional reconstructions using multiple marker proteins confirmed that the human intrahepatic biliary tree forms through several developmental stages involving an initial transition of primitive hepatocytes into cholangiocytes shaping the ductal plate followed by a process of maturation and remodeling where the intrahepatic biliary tree develops through an asymmetrical form of cholangiocyte tubulogenesis.

Conclusions
The developed protocols provide a novel and sophisticated three-dimensional visualization of vessels and protein expression in human liver during development and disease.
Whole-exome sequencing of DNA from peripheral blood mononuclear cells (PBMC) and EBV-transformed lymphocytes from the same donor
Authors: Londin Eric R , Keller Margaret A , D'Andrea Michael R , Delgrosso Kathleen , Ertel Adam , Surrey Saul , Fortina Paolo 
Published: September 2011

Abstract

Background
The creation of lymphoblastoid cell lines (LCLs) through Epstein-Barr virus (EBV) transformation of B-lymphocytes can result in a valuable biomaterial for cell biology research and a renewable source of DNA. While LCLs have been used extensively in cellular and genetic studies, the process of cell transformation and expansion during culturing may introduce genomic changes that may impact their use and the interpretation of subsequent genetic findings.

Results
We performed whole exome sequencing on a tetrad family using DNA derived from peripheral blood mononuclear cells (PBMCs) and LCLs from each individual. We generated over 4.7 GB of mappable sequence to a 125X read coverage per sample. An average of 19,354 genetic variants were identified. Comparison of the two DNA sources from each individual showed an average concordance rate of 95.69%. By lowering the variant calling parameters, the concordance rate between the paired samples increased to 99.82%. Sanger sequencing of a subset of the remaining discordant variants did confirm the presence of de novo mutations arising in LCLs.

Conclusions
By varying software stringency parameters, we identified 99% concordance between DNA sequences derived from the two different sources from the same donors. These results suggest that LCLs are an appropriate representation of the genetic material of the donor and suggest that EBV transformation can result in low-level generation of de novo mutations. Therefore, use of PBMC or early passage EBV-transformed cells is recommended. These findings have broad-reaching implications, as there are thousands of LCLs in public biorepositories and individual laboratories.
Semiallogenic fusions of MSI+tumor cells and activated B cells induce MSI-specific T cell responses
Authors: Garbe Yvette , Klier Ulrike , Linnebacher Michael 
Published: September 2011

Abstract

Background
Various strategies have been developed to transfer tumor-specific antigens into antigen presenting cells in order to induce cytotoxic T cell responses against tumor cells. One approach uses cellular vaccines based on fusions of autologous antigen presenting cells and allogeneic tumor cells. The fusion cells combine antigenicity of the tumor cell with optimal immunostimulatory capacity of the antigen presenting cells.
Microsatellite instability caused by mutational inactivation of DNA mismatch repair genes results in translational frameshifts when affecting coding regions. It has been shown by us and others that these mutant proteins lead to the presentation of immunogenic frameshift peptides that are - in principle - recognized by a multiplicity of effector T cells.

Methods
We chose microsatellite instability-induced frameshift antigens as ideal to test for induction of tumor specific T cell responses by semiallogenic fusions of microsatellite instable carcinoma cells with CD40-activated B cells. Two fusion clones of HCT116 with activated B cells were selected for stimulation of T cells autologous to the B cell fusion partner. Outgrowing T cells were phenotyped and tested in functional assays.

Results
The fusion clones expressed frameshift antigens as well as high amounts of MHC and costimulatory molecules. Autologous T cells stimulated with these fusions were predominantly CD4+, activated, and reacted specifically against the fusion clones and also against the tumor cell fusion partner. Interestingly, a response toward 6 frameshift-derived peptides (of 14 tested) could be observed.

Conclusion
Cellular fusions of MSI+ carcinoma cells and activated B cells combine the antigen-presenting capacity of the B cell with the antigenic repertoire of the carcinoma cell. They present frameshift-derived peptides and can induce specific and fully functional T cells recognizing not only fusion cells but also the carcinoma cells. These hybrid cells may have great potential for cellular immunotherapy and this approach should be further analyzed in preclinical as well as clinical trials. Moreover, this is the first report on the induction of frameshift-specific T cell responses without the use of synthetic peptides.
Use of silver nanoparticles increased inhibition of cell-associated HIV-1 infection by neutralizing antibodies developed against HIV-1 envelope proteins
Authors: Lara Humberto H , Ixtepan-Turrent Liliana , Garza Treviño Elsa N , Singh Dinesh K 
Published: September 2011

Abstract

Background
HIV/AIDS pandemic is a worldwide public health issue. There is a need for new approaches to develop new antiviral compounds or other therapeutic strategies to limit viral transmission. The envelope glycoproteins gp120 and gp41 of HIV are the main targets for both silver nanoparticles (AgNPs) and neutralizing antibodies. There is an urgency to optimize the efficiency of the neutralizing antibodies (NABs). In this study, we demonstrated that there is an additive effect between the four NABs and AgNPs when combined against cell-associated HIV-1 infection in vitro

Results
Four NABs (Monoclonal antibody to HIV-1 gp41 126-7, HIV-1 gp120 Antiserum PB1 Sub 2, HIV-1 gp120 Antiserum PB1, HIV-1 gp120 Monoclonal Antibody F425 B4e8) with or without AgNPs of 30-50 nm in size were tested against cell free and cell-associated HIVIIIB virus. All NABs inhibited HIV-1 cell free infection at a dose response manner, but with AgNPs an antiviral additive effect was not achieved Although there was no inhibition of infection with cell-associated virus by the NABs itself, AgNPs alone were able to inhibit cell associated virus infection and more importantly, when mixed together with NABs they inhibited the HIV-1 cell associated infection in an additive manner.

Discussion
The most attractive strategies to deal with the HIV problem are the development of a prophylactic vaccine and the development of effective topical vaginal microbicide. For two decades a potent vaccine that inhibits transmission of infection of HIV has been searched. There are vaccines that elicit NABs but none of them has the efficacy to stop transmission of HIV-1 infection. We propose that with the addition of AgNPs, NABs will have an additive effect and become more potent to inhibit cell-associated HIV-1 transmission/infection.

Conclusions
The addition of AgNPs to NABs has significantly increased the neutralizing potency of NABs in prevention of cell-associated HIV-1 transmission/infection. Further exploration is required to standardize potentiation of NABs by AgNPs. It is also required to evaluate in vivo toxicity of AgNPs before AgNPs could be incorporated in any antiviral vaginal creams.