bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application of response surface methodology for optimization of ionic liquid-based dispersive liquid–liquid microextraction of cadmium from water samples
Authors: Rajabi M , Kamalabadi M , Jamali MR , Zolgharnein J , Asanjarani N 
Published: August 2012

A new, rapid, and simple method for the determination of cadmium in water samples was developed using ionic liquid-based dispersive liquid–liquid microextraction (IL-DLLME) coupled to flame atomic absorption spectrometry (FAAS). In the proposed approach, 2-(5-boromo-2-pyridylazo)-5-(diethyamino) phenol was used as a chelating agent and 1-hexyl-3-methylimidazolium bis(trifluoro methylsulfonyl)imide and acetone were selected as extraction and dispersive solvents, respectively. Sample pH, concentration of chelating agent, amount of ionic liquid (extraction solvent), disperser solvent volume, extraction time, salt effect, and centrifugation speed were selected as interested variables in IL-DLLME process. The significant variables affecting the extraction efficiency were determined using a Placket–Burman design. Thereafter, the significant variables were optimized using a Box–Behnken design and the quadratic model between the dependent and the independent variables was built. The optimum experimental conditions obtained from this statistical evaluation included: pH: 6.7; concentration of chelating agent: 1.1 × 10−3 mol L−1; and ionic liquid: 50.0 mg. Under the optimum conditions, the preconcentration factor obtained was 100. Calibration graph was linear in the range of 0.2–60 µg L−1 with correlation coefficient of 0.9992. The limit of detection was 0.06 µg L−1, which is lower than other reported approaches applied to the determination of cadmium using FAAS. The relative SD ( n = 8) was 2.4%. The proposed method was successfully applied to the determination of trace amounts of cadmium in the real water samples with satisfactory results.
Effects of plerixafor in combination with BCR-ABL kinase inhibition in a murine model of CML
Authors: Agarwal Anupriya , Fleischman Angela G. , Petersen Curtis L. , MacKenzie Ryan , Luty Samuel , Loriaux Marc , Druker Brian J. , Woltjer Randall L. , Deininger Michael W. 
Published: August 2012

Abstract
Sequestration in the bone marrow niche may allow leukemic stem cells to evade exposure to drugs. Because the CXCR4/SDF-1 axis is an important mechanism of leukemic stem cell interaction with marrow stroma, we tested whether plerixafor, an antagonist of CXCR4, may dislodge chronic myeloid leukemia (CML) cells from the niche, sensitizing them to tyrosine kinase inhibitors. We initially treated mice with retrovirally induced CML-like disease with imatinib plus plerixafor. Plerixafor mobilized CXCR4+ cells, but no difference was observed in leukemia burden, possibly reflecting insufficient disease control by imatinib. In a second series of experiments, we tested the combination of plerixafor with dasatinib in the same as well as an attenuated CML model. Despite much improved leukemia control, plerixafor failed to reduce leukemia burden over dasatinib alone. In addition, mice receiving plerixafor had an increased incidence of neurologic symptoms in association with CNS infiltration by BCR-ABL–expressing cells. We conclude that plerixafor is ineffective in reducing leukemia burden in this model but promotes CNS infiltration. Beneficial effects of combining tyrosine kinase inhibitors with plerixafor may be observed in a situation of minimal residual disease, but caution is warranted when disease control is incomplete.
Endogenous HLA class II epitopes that are immunogenic in vivo show distinct behavior toward HLA-DM and its natural inhibitor HLA-DO
Authors: Kremer Anita N. , van der Meijden Edith D. , Honders Maria W. , Goeman Jelle J. , Wiertz Emmanuel J. H. J. , Falkenburg J. H. Frederik , Griffioen Marieke 
Published: August 2012

AbstractCD4+ T cells play a central role in adaptive immunity. The acknowledgment of their cytolytic effector function and the finding that endogenous antigens can enter the HLA class II processing pathway make CD4+ T cells promising tools for immunotherapy. Expression of HLA class II and endogenous antigen, however, does not always correlate with T-cell recognition. We therefore investigated processing and presentation of endogenous HLA class II epitopes that induced CD4+ T cells during in vivo immune responses. We demonstrate that the peptide editor HLA-DM allowed antigen presentation of some (DM-resistant antigens) but abolished surface expression of other natural HLA class II epitopes (DM-sensitive antigens). DM sensitivity was shown to be epitope specific, mediated via interaction between HLA-DM and the HLA-DR restriction molecule, and reversible by HLA-DO. Because of the restricted expression of HLA-DO, presentation of DM-sensitive antigens was limited to professional antigen-presenting cells, whereas DM-resistant epitopes were expressed on all HLA class II–expressing cells. In conclusion, our data provide novel insights into the presentation of endogenous HLA class II epitopes and identify intracellular antigen processing and presentation as a critical factor for CD4+ T-cell recognition. This opens perspectives to exploit selective processing capacities as a new approach for targeted immunotherapy.
ROCK suppression promotes differentiation and expansion of endothelial cells from embryonic stem cell–derived Flk1+ mesodermal precursor cells
Authors: Joo Hyung Joon , Choi Dong-Kyu , Lim Joon Seo , Park Jin-Sung , Lee Seung-Hun , Song Sukhyun , Shin Jennifer H. , Lim Do-Sun , Kim Injune , Hwang Ki-Chul , Koh Gou Young 
Published: August 2012

AbstractSuccessful differentiation and expansion of endothelial cells (ECs) from embryonic stem cell (ESC)–derived Flk1+ mesodermal precursor cells (MPCs) requires supplementation of vascular endothelial growth factor-A (VEGF-A). While analyzing VEGF-A/VEGFR2 downstream signaling pathway that underlies the VEGF-A-induced differentiation and expansion of ECs, we fortuitously found that Rho-associated protein kinase (ROCK) inhibitor Y27632 profoundly promoted the differentiation and expansion of ECs from Flk1+ MPCs while reducing the differentiation and expansion of mural cells. The ROCK suppression-induced expansion of ECs appears to have resulted from promotion of proliferation of ECs via activation of PI3-kinase-Akt signaling. The ECs obtained by the combination of ROCK suppression and VEGF-A supplementation faithfully expressed most pan-EC surface makers, and phenotypic analyses revealed that they were differentiated toward arterial EC. Further incubation of the ICAM2+ ECs with Y27632 and VEGF-A for 2 days promoted expansion of ECs by 6.5-fold compared with those incubated with only VEGF-A. Importantly, the ROCK suppression-induced ECs displayed neovasculogenic abilities in vitro and in vivo. Thus, supplementation of ROCK inhibitor Y27632 along with VEGF-A in 2D Matrigel culture system provides a simple, efficient, and versatile method for obtaining ample amount of ESC-derived ECs at high purity suitable for use in therapeutic neovascularization.
Maintenance therapy with bortezomib plus thalidomide or bortezomib plus prednisone in elderly multiple myeloma patients included in the GEM2005MAS65 trial
Authors: Mateos María-Victoria , Oriol Albert , Martínez-López Joaquín , Gutiérrez Norma , Teruel Ana-Isabel , López de la Guía Ana , López Javier , Bengoechea Enrique , Pérez Montserrat , Polo Marta , Palomera Luis , de Arriba Felipe , González Yolanda , Hernández Jose-Mariano , Granell Miquel , Bello José-Luis , Bargay Joan , Peñalver Francisco-Javier , Ribera José-María , Martín-Mateos María-Luisa , García-Sanz Ramón , Lahuerta Juan-José , Bladé Joan , San-Miguel Jesús F. 
Published: August 2012

Abstract
Maintenance therapy has become a hot field in myeloma, and it may be particularly relevant in elderly patients because the major benefit results from the initial therapy. We report the results of a randomized comparison of maintenance with bortezomib plus thalidomide (VT) or prednisone (VP) in 178 elderly untreated myeloma patients who had received 6 induction cycles with bortezomib plus either melphalan and prednisone or thalidomide and prednisone. The complete response (CR) rate increased from 24% after induction up to 42%, higher for VT versus VP (46% vs 39%). Median progression-free survival (PFS) was superior for VT (39 months) compared with VP (32 months) and overall survival (OS) was also longer in VT patients compared with VP (5-year OS of 69% and 50%, respectively) but the differences did not reach statistical significance. CR achievement was associated with a significantly longer PFS (P < .001) and 5-year OS (P < .001). The incidence of G3-4 peripheral neuropathy was 9% for VT and 3% for VP. Unfortunately, this approach was not able to overcome the adverse prognosis of cytogenetic abnormalities. In summary, these maintenance regimens result in a significant increase in CR rate, remarkably long PFS, and acceptable toxicity profile. The trial is registered at www.clinicaltrials.gov as NCT00443235.
B cells from patients with chronic GVHD are activated and primed for survival via BAFF-mediated pathways
Authors: Allen Jessica L. , Fore Matthew S. , Wooten Jenna , Roehrs Philip A. , Bhuiya Nazmim S. , Hoffert Todd , Sharf Andrew , Deal Allison M. , Armistead Paul , Coghill James , Gabriel Don A. , Irons Robert , Essenmacher Amber , Shea Thomas C. , Richards Kristy , Cutler Corey , Ritz Jerome , Serody Jonathan , Baldwin Albert S. , Sarantopoulos Stefanie 
Published: August 2012

Abstract
Recent data reveal an important role for B cells in the pathogenesis of chronic GVHD (cGVHD). Patients with cGVHD have delayed B-cell reconstitution and elevated BAFF to B-cell ratios compared to patients without cGVHD. The mechanisms promoting and sustaining B-cell activation in this disease, however, remain unknown. As BAFF increases murine B-cell metabolism and survival and maintains autoreactive B-cell clones, we performed ex vivo analyses of peripheral B cells from 51 patients who either had or did not have active cGVHD and were greater than 1 year from the time of allogeneic hematopoietic stem cell transplantation. We found that B cells from patients with active cGVHD were in a heightened metabolic state and were resistant to apoptosis. Exogenous BAFF treatment amplified cell size and survival in B cells from these patients. We found significantly increased signaling through ERK and AKT that associated with decreased levels of proapoptotic Bim, suggesting a mechanistic link between elevated BAFF levels and aberrant B-cell survival. Thus, we identify a role for BAFF in the pathogenesis of cGVHD and define B-cell activation and survival pathways suitable for novel therapeutic development in cGVHD.
Inhibitory effects of 405 nm irradiation on Chlamydia trachomatis growth and characterization of the ensuing inflammatory response in HeLa cells
Authors: Wasson Cassandra J , Zourelias Jessica L , Aardsma Nathan A , Eells Janis T , Ganger Mike T , Schober Justine M , Skwor Troy A 
Published: August 2012

Abstract

Background

Chlamydia trachomatis is an intracellular bacterium that resides in the conjunctival and reproductive tract mucosae and is responsible for an array of acute and chronic diseases. A percentage of these infections persist even after use of antibiotics, suggesting the need for alternative treatments. Previous studies have demonstrated anti-bacterial effects using different wavelengths of visible light at varying energy densities, though only against extracellular bacteria. We investigated the effects of visible light (405 and 670 nm) irradiation via light emitting diode (LEDs) on chlamydial growth in endocervical epithelial cells, HeLa, during active and penicillin-induced persistent infections. Furthermore, we analyzed the effect of this photo treatment on the ensuing secretion of IL-6 and CCL2, two pro-inflammatory cytokines that have previously been identified as immunopathologic components associated with trichiasis in vivo.

Results

C. trachomatis-infected HeLa cells were treated with 405 or 670 nm irradiation at varying energy densities (0 – 20 J/cm2). Bacterial growth was assessed by quantitative real-time PCR analyzing the 16S: GAPDH ratio, while cell-free supernatants were examined for IL-6 and monocyte chemoattractant protein-1 (CCL2) production. Our results demonstrated a significant dose-dependent inhibitory effect on chlamydial growth during both active and persistent infections following 405 nm irradiation. Diminished bacterial load corresponded to lower IL-6 concentrations, but was not related to CCL2 levels. In vitro modeling of a persistent C. trachomatis infection induced by penicillin demonstrated significantly elevated IL-6 levels compared to C. trachomatis infection alone, though 405 nm irradiation had a minimal effect on this production.

Conclusion
Together these results identify novel inhibitory effects of 405 nm violet light on the bacterial growth of intracellular bacterium C. trachomatis in vitro, which also coincides with diminished levels of the pro-inflammatory cytokine IL-6.
Dairy calcium intake and lifestyle risk factors for bone loss in hiv-infected and uninfected mediterranean subjects
Authors: Vecchi Valentina Li , Soresi Maurizio , Giannitrapani Lydia , Mazzola Giovanni , La Sala Sara , Tramuto Fabio , Caruso Giuseppe , Colomba Claudia , Mansueto Pasquale , Madonia Simona , Montalto Giuseppe , Di Carlo Paola 
Published: August 2012

Abstract

Background
Despite the reported high prevalence of osteoporosis in the human immunodeficiency virus (HIV)-population, there have been no previous studies examining dairy calcium intake and bone mineral density (BMD) in HIV-subjects.
We assessed the prevalence of low BMD in HIV-infected and uninfected subjects and analyzed the effects of calcium intake, lifestyle and HIV-related risk factors on BMD.

Methods
One hundred and twelve HIV-infected subjects were consecutively enrolled. Seventy- six HIV-uninfected subjects matched for age and sex were enrolled as the control group. The HIV-subjects were interviewed about lifestyle habits and completed a weekly food-frequency questionnaire to estimate calcium intake. HIV-RNA, CD4+ T-cell count and data on antiretroviral therapy were also recorded. Both biochemical bone turnover markers and BMD, assessed by dual-energy radiographic absorptiometry (DXA) were recorded in the HIV-cases and controls. We also calculated the 10-year fracture risks using the WHO FRAX equation.

Results
Osteoporosis prevalence was significantly higher in the HIV-cases than controls (p < 0.05). BMI values were positively correlated with BMD (p < 0.05). Vitamin D levels were lower in the HIV-subjects (p < 0.02). No correlation was found with daily calcium intake.
BMI values were significantly correlated with dairy intake quartiles (p < 0.003). In HIV-subjects, the mean of FRAX score was 1.2 % for hip and 4.7 % for major osteoporotic fractures. On multivariate analysis of the lumbar spine DXA T-score, age (p < 0.005) and HIV/hepatitis C virus co-infection (p < 0.0001) were negatively correlated with BMD, while yogurt intake was a protective predictor of BMD (p < 0.05). In the femur DXA T-score, age (p < 0.01), nadir CD4 + T-cell count < 200 cells/μL (p < 0.05) and drug addiction ( p < 0.0001) were negatively correlated with BMD.

Conclusions
Among the foods rich in calcium, yogurt was a protective predictor of BMD in HIV-subjects. HIV/HCV co-infection, nadir CD4 + T-cell count < 200 cells/μL and drug addiction were independent predictors of severe BMD. Promoting behavioral changes in food intake and lifestyle, aimed at the primary prevention of bone disease in the chronically-infected subjects seems to be essential for implementing medical intervention in these cases.
BAC CGH-array identified specific small-scale genomic imbalances in diploid DMBA-induced rat mammary tumors
Authors: Samuelson Emma , Karlsson Sara , Partheen Karolina , Nilsson Staffan , Szpirer Claude , Behboudi Afrouz 
Published: August 2012

Abstract

Background
Development of breast cancer is a multistage process influenced by hormonal and environmental factors as well as by genetic background. The search for genes underlying this malignancy has recently been highly productive, but the etiology behind this complex disease is still not understood. In studies using animal cancer models, heterogeneity of the genetic background and environmental factors is reduced and thus analysis and identification of genetic aberrations in tumors may become easier. To identify chromosomal regions potentially involved in the initiation and progression of mammary cancer, in the present work we subjected a subset of experimental mammary tumors to cytogenetic and molecular genetic analysis.

Methods
Mammary tumors were induced with DMBA (7,12-dimethylbenz[a]anthrazene) in female rats from the susceptible SPRD-Cu3 strain and from crosses and backcrosses between this strain and the resistant WKY strain. We first produced a general overview of chromosomal aberrations in the tumors using conventional kartyotyping (G-banding) and Comparative Genome Hybridization (CGH) analyses. Particular chromosomal changes were then analyzed in more details using an in-house developed BAC (bacterial artificial chromosome) CGH-array platform.

Results
Tumors appeared to be diploid by conventional karyotyping, however several sub-microscopic chromosome gains or losses in the tumor material were identified by BAC CGH-array analysis. An oncogenetic tree analysis based on the BAC CGH-array data suggested gain of rat chromosome (RNO) band 12q11, loss of RNO5q32 or RNO6q21 as the earliest events in the development of these mammary tumors.

Conclusions
Some of the identified changes appear to be more specific for DMBA-induced mammary tumors and some are similar to those previously reported in ACI rat model for estradiol-induced mammary tumors. The later group of changes is more interesting, since they may represent anomalies that involve genes with a critical role in mammary tumor development. Genetic changes identified in this work are at very small scales and thus may provide a more feasible basis for the identification of the target gene(s). Identification of the genes underlying these chromosome changes can provide new insights to the mechanisms of mammary carcinogenesis.
Hepatitis B virus X protein suppresses caveolin-1 expression in hepatocellular carcinoma by regulating DNA methylation
Authors: Yan Jun , Lu Qian , Dong Jiahong , Li Xiaowu , Ma Kuansheng , Cai Lei 
Published: August 2012

Abstract

Background
To understand the molecular mechanisms of caveolin-1 downregulation by hepatitis B virus X protein (HBx).

Methods
The DNA methylation status of the caveolin-1 promoter was examined by nested methylation-specific PCR of 33 hepatitis B virus (HBV)-infected hepatocellular carcinoma (HCC) samples. The SMMC-7721 hepatoma cell line was transfected with a recombinant HBx adenoviral vector, and the effects of HBx protein on caveolin-1 expression and promoter methylation were examined and confirmed by sequencing. A reporter gene containing the caveolin-1 promoter region was constructed, and the effects of HBx on the transcriptional activity of the promoter were also studied.

Results
Methylation of the caveolin-1 promoter was detected in 84.8% (28/33) of HBV-infected HCC samples. Expression of caveolin-1 was significantly downregulated (P = 0.022), and multiple CpG sites in the promoter region of caveolin-1 were methylated in SMMC-7721 cells after HBx transfection. Transfected HBx significantly suppressed caveolin-1 promoter activity (P = 0.001).

Conclusions
HBx protein induces methylation of the caveolin-1 promoter region and suppresses its expression.
Solar ultraviolet-B radiation and vitamin D: a cross-sectional population-based study using data from the 2007 to 2009 Canadian Health Measures Survey
Authors: Greenfield Jamie A , Park Philip S , Farahani Ellie , Malik Suneil , Vieth Reinhold , McFarlane Norman A , Shepherd Theodore G , Knight Julia A 
Published: August 2012

Abstract

Background
Exposure to solar ultraviolet-B (UV-B) radiation is a major source of vitamin D3. Chemistry climate models project decreases in ground-level solar erythemal UV over the current century. It is unclear what impact this will have on vitamin D status at the population level. The purpose of this study was to measure the association between ground-level solar UV-B and serum concentrations of 25-hydroxyvitamin D (25(OH)D) using a secondary analysis of the 2007 to 2009 Canadian Health Measures Survey (CHMS).

Methods
Blood samples collected from individuals aged 12 to 79 years sampled across Canada were analyzed for 25(OH)D (n = 4,398). Solar UV-B irradiance was calculated for the 15 CHMS collection sites using the Tropospheric Ultraviolet and Visible Radiation Model. Multivariable linear regression was used to evaluate the association between 25(OH)D and solar UV-B adjusted for other predictors and to explore effect modification.

Results
Cumulative solar UV-B irradiance averaged over 91 days (91-day UV-B) prior to blood draw correlated significantly with 25(OH)D. Independent of other predictors, a 1 kJ/m2 increase in 91-day UV-B was associated with a significant 0.5 nmol/L (95% CI 0.3-0.8) increase in mean 25(OH)D (P = 0.0001). The relationship was stronger among younger individuals and those spending more time outdoors. Based on current projections of decreases in ground-level solar UV-B, we predict less than a 1 nmol/L decrease in mean 25(OH)D for the population.

Conclusions
In Canada, cumulative exposure to ambient solar UV-B has a small but significant association with 25(OH)D concentrations. Public health messages to improve vitamin D status should target safe sun exposure with sunscreen use, and also enhanced dietary and supplemental intake and maintenance of a healthy body weight.
Changes of gluteus medius muscle in the adult patients with unilateral developmental dysplasia of the hip
Authors: Liu RuiYu , Wen XiaoDong , Tong ZhiQin , Wang KunZheng , Wang ChunSheng 
Published: August 2012

AbstractBackgroundThe gluteus medius muscle is essential for gait and hip stability. Changes that occur in the gluteus medius muscles in patients with developmental dysplasia of the hip (DDH) are not well understood. A better understanding of DDH related changes will have positive repercussions toward hip soft tissue reconstruction.Methods19 adult patients with unilateral DDH scheduled for total hip arthroplasty were assessed for: cross-sectional area (CSA), radiological density (RD) and the length of gluteus medius using computed tomograhpy(CT) (scanned before THA). Hip abductor moment arm and gluteus medius activation angle were also measuredviahip anteroposterior radiographs.ResultsBoth CSA and RD of gluteus medius muscle were significantly reduced (p < 0.05) in the affected hip compared to the control. In the affected hip, the length of the gluteus medius muscle was reduced by 8-11 % (p < 0.05) while the gluteus medius activation angle was significantly increased (p < 0.05) and the hip abductor moment arm was decreased (p < 0.05).ConclusionsThe gluteus medius showed substantial loss of CSA, RD as well as decreased length in patients with DDH in the affected hip. These changes should be considered in both hip reconstruction and postoperative rehabilitation training in patients with DDH.