bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dietary intake in the Personalized Medicine Research Project: a resource for studies of gene-diet interaction
Authors: Strobush Lacie , Berg Richard , Cross Deanna , Foth Wendy , Kitchner Terrie , Coleman Laura , McCarty Catherine A 
Published: February 2011

Abstract

Background
To describe the dietary intake of participants in the Personalized Medicine Research Project (PMRP), and to quantify differences in nutrient intake by smoking status and APOE4-a genetic marker that has been shown to modify the association between risk factors and outcomes.

Methods
The PMRP is a population-based DNA, plasma and serum biobank of more than 20,000 adults aged 18 years and older in central Wisconsin. A questionnaire at enrollment captures demographic information as well as self-reported smoking and alcohol intake. The protocol was amended to include the collection of dietary intake and physical activity via self-reported questionnaires: the National Cancer Institute 124-item Diet History Questionnaire and the Baecke Physical Activity Questionnaire. These questionnaires were mailed out to previously enrolled participants. APOE was genotyped in all subjects.

Results
The response rate to the mailed questionnaires was 68.2% for subjects who could still be contacted (alive with known address). Participants ranged in age from 18 to 98 years (mean 54.7) and 61% were female. Dietary intake is variable when comparing gender, age, smoking, and APOE4. Over 50% of females are dietary supplement users; females have higher supplement intake than males, but both have increasing supplement use as age increases. Food energy, total fat, cholesterol, protein, and alcohol intake decreases as both males and females age. Female smokers had higher macronutrient intake, whereas male nonsmokers had higher macronutrient intake. Nonsmokers in both genders use more supplements. In females, nonsmokers and smokers with APOE4 had higher supplement use. In males, nonsmokers with APOE4 had higher supplement use between ages 18-39 only, and lower supplement use at ages above 39. Male smokers with APOE4 had lower supplement use.

Conclusion
Dietary intake in PMRP subjects is relatively consistent with data from the National Health and Nutrition Examination Survey (NHANES). Findings suggest a possible correlation between the use of supplements and APOE4. The PMRP dietary data can benefit studies of gene-environment interactions and the development of common diseases.
Effect of nitrogen-rich cell culture surfaces on type X collagen expression by bovine growth plate chondrocytes
Authors: Petit Alain , Demers Caroline N , Girard-Lauriault Pierre-Luc , Stachura Dorothy , Wertheimer Michael R , Antoniou John , Mwale Fackson 
Published: February 2011

Abstract

Background
Recent evidence indicates that osteoarthritis (OA) may be a systemic disease since mesenchymal stem cells (MSCs) from OA patients express type X collagen, a marker of late stage chondrocyte hypertrophy (associated with endochondral ossification). We recently showed that the expression of type X collagen was suppressed when MSCs from OA patients were cultured on nitrogen (N)-rich plasma polymer layers, which we call "PPE:N" (N-doped plasma-polymerized ethylene, containing up to 36 atomic percentage (at.% ) of N.

Methods
In the present study, we examined the expression of type X collagen in fetal bovine growth plate chondrocytes (containing hypertrophic chondrocytes) cultured on PPE:N. We also studied the effect of PPE:N on the expression of matrix molecules such as type II collagen and aggrecan, as well as on proteases (matrix metalloproteinase-13 (MMP-13) and molecules implicated in cell division (cyclin B2). Two other culture surfaces, "hydrophilic" polystyrene (PS, regular culture dishes) and nitrogen-containing cation polystyrene (Primaria®), were also investigated for comparison.

Results
Results showed that type X collagen mRNA levels were suppressed when cultured for 4 days on PPE:N, suggesting that type X collagen is regulated similarly in hypertrophic chondrocytes and in human MSCs from OA patients. However, the levels of type X collagen mRNA almost returned to control value after 20 days in culture on these surfaces. Culture on the various surfaces had no significant effects on type II collagen, aggrecan, MMP-13, and cyclin B2 mRNA levels.

Conclusion
Hypertrophy is diminished by culturing growth plate chondrocytes on nitrogen-rich surfaces, a mechanism that is beneficial for MSC chondrogenesis. Furthermore, one major advantage of such "intelligent surfaces" over recombinant growth factors for tissue engineering and cartilage repair is potentially large cost-saving.
Area-aggregated assessments of perceived environmental attributes may overcome single-source bias in studies of green environments and health: results from a cross-sectional survey in southern Sweden
Authors: de Jong Kim , Albin Maria , Skärbäck Erik , Grahn Patrik , Wadbro John , Merlo Juan , Björk Jonas 
Published: February 2011

Abstract

Background
Most studies assessing health effects of neighborhood characteristics either use self-reports or objective assessments of the environment, the latter often based on Geographical Information Systems (GIS). While objective measures require detailed landscape data, self-assessments may yield confounded results. In this study we demonstrate how self-assessments of green neighborhood environments aggregated to narrow area units may serve as an appealing compromise between objective measures and individual self-assessments.

Methods
The study uses cross-sectional data (N = 24,847) from a public health survey conducted in the county of Scania, southern Sweden, in 2008 and validates the Scania Green Score (SGS), a new index comprising five self-reported green neighborhood qualities (Culture, Lush, Serene, Spacious and Wild). The same qualities were also assessed objectively using landscape data and GIS. A multilevel (ecometric) model was used to aggregate individual self-reports to assessments of perceived green environmental attributes for areas of 1,000 square meters. We assessed convergent and concurrent validity for self-assessments of the five items separately and for the sum score, individually and area-aggregated.

Results
Correlations between the index scores based on self-assessments and the corresponding objective assessments were clearly present, indicating convergent validity, but the agreement was low. The correlation was even more evident for the area-aggregated SGS. All three scores (individual SGS, area-aggregated SGS and GIS index score) were associated with neighborhood satisfaction, indicating concurrent validity. However, while individual SGS was associated with vitality, this association was not present for aggregated SGS and the GIS-index score, suggesting confounding (single-source bias) when individual SGS was used.

Conclusions
Perceived and objectively assessed qualities of the green neighborhood environment correlate but do not agree. An index score based on self-reports but aggregated to narrow area units can be a valid approach to assess perceived green neighborhood qualities in settings where objective assessments are not possible or feasible.
Lymphocyte deficiency limits Epstein-Barr virus latent membrane protein 1 induced chronic inflammation and carcinogenic pathology in vivo
Authors: Hannigan Adele , Qureshi Asif M , Nixon Colin , Tsimbouri Penelope M , Jones Sarah , Philbey Adrian W , Wilson Joanna B 
Published: February 2011

AbstractBackgroundThe importance of the malignant cell environment to its growth and survival is becoming increasingly apparent, with dynamic cross talk between the neoplastic cell, the leukocyte infiltrate and the stroma. Most cancers are accompanied by leukocyte infiltration which, contrary to an anticipated immuno-protective role, could be contributing to tumour development and cancer progression. Epstein-Barr virus (EBV) associated cancers, including nasopharyngeal carcinoma and Hodgkin's Disease, show a considerable leukocyte infiltration which surrounds the neoplastic cells, raising the questions as to what role these cells play in either restricting or supporting the tumour and what draws the cells into the tumour. In order to begin to address this we have studied a transgenic model of multistage carcinogenesis with epithelial expression of the EBV primary oncoprotein, latent membrane protein 1 (LMP1). LMP1 is expressed particularly in the skin, which develops a hyperplastic pathology soon after birth.ResultsThe pathology advances with time leading to erosive dermatitis which is inflamed with a mixed infiltrate involving activated CD8+ T-cells, CD4+ T-cells including CD4+/CD25+/FoxP3+ Treg cells, mast cells and neutrophils. Also significant dermal deposition of immunoglobulin-G (IgG) is observed as the pathology advances. Along with NF-kappaB activation, STAT3, a central factor in inflammation regulation, is activated in the transgenic tissue. Several inflammatory factors are subsequently upregulated, notably CD30 and its ligand CD153, also leukocyte trafficking factors including CXCL10, CXCL13, L-selectin and TGFβ1, and inflammatory cytokines including IL-1β, IL-3 and the murine IL-8 analogues CXCL1, CXCL2 and CXCL5-6, amongst others. The crucial role of mature T- and/or B-lymphocytes in the advancing pathology is demonstrated by their elimination, which precludes mast cell infiltration and limits the pathology to an early, benign stage.ConclusionsLMP1 can lead to the activation of several key factors mediating proliferation, angiogenesis and inflammationin vivo. With the initiation of an inflammatory programme, leukocyte recruitment follows which then itself contributes to the progressing pathology in these transgenic mice, with a pivotal role for B-and/or T-cells in the process. The model suggests a basis for the leukocyte infiltrate observed in EBV-associated cancer and its supporting role, as well as potential points for therapeutic intervention.
Cyr61/CCN1 signaling is critical for epithelial-mesenchymal transition and stemness and promotes pancreatic carcinogenesis
Authors: Haque Inamul , Mehta Smita , Majumder Monami , Dhar Kakali , De Archana , McGregor Douglas , Van Veldhuizen Peter J , Banerjee Sushanta K , Banerjee Snigdha 
Published: February 2011

Abstract

Background
Despite recent advances in outlining the mechanisms involved in pancreatic carcinogenesis, precise molecular pathways and cellular lineage specification remains incompletely understood.

Results
We show here that Cyr61/CCN1 play a critical role in pancreatic carcinogenesis through the induction of EMT and stemness. Cyr61 mRNA and protein were detected in the early precursor lesions and their expression intensified with disease progression. Cyr61/CCN1 expression was also detected in different pancreatic cancer cell lines. The aggressive cell lines, in which the expressions of mesenchymal/stem cell molecular markers are predominant; exhibit more Cyr61/CCN1 expression. Cyr61 expression is exorbitantly higher in cancer stem/tumor initiating Panc-1-side-population (SP) cells. Upon Cyr61/CCN1 silencing, the aggressive behaviors are reduced by obliterating interlinking pathobiological events such as reversing the EMT, blocking the expression of stem-cell-like traits and inhibiting migration. In contrast, addition of Cyr61 protein in culture medium augments EMT and stemness features in relatively less aggressive BxPC3 pancreatic cancer cells. Using a xenograft model we demonstrated that cyr61/CCN1 silencing in Panc-1-SP cells reverses the stemness features and tumor initiating potency of these cells. Moreover, our results imply a miRNA-based mechanism for the regulation of aggressive behaviors of pancreatic cancer cells by Cyr61/CCN1.

Conclusions
In conclusion, the discovery of the involvement of Cyr61/CCN1 in pancreatic carcinogenesis may represent an important marker for PDAC and suggests Cyr61/CCN1 can be a potential cancer therapeutic target.
High-fat diet and glucocorticoid treatment cause hyperglycemia associated with adiponectin receptor alterations
Authors: de Oliveira Cristiane , de Mattos Ana BM , Biz Carolina , Oyama Lila M , Ribeiro Eliane B , Oller do Nascimento Cláudia Maria 
Published: February 2011

Abstract

Background
Adiponectin is the most abundant plasma protein synthesized for the most part in adipose tissue, and it is an insulin-sensitive hormone, playing a central role in glucose and lipid metabolism. In addition, it increases fatty acid oxidation in the muscle and potentiates insulin inhibition of hepatic gluconeogenesis. Two adiponectin receptors have been identified: AdipoR1 is the major receptor expressed in skeletal muscle, whereas AdipoR2 is mainly expressed in liver. Consumption of high levels of dietary fat is thought to be a major factor in the promotion of obesity and insulin resistance. Excessive levels of cortisol are characterized by the symptoms of abdominal obesity, hypertension, glucose intolerance or diabetes and dyslipidemia; of note, all of these features are shared by the condition of insulin resistance. Although it has been shown that glucocorticoids inhibit adiponectin expression in vitro and in vivo, little is known about the regulation of adiponectin receptors. The link between glucocorticoids and insulin resistance may involve the adiponectin receptors and adrenalectomy might play a role not only in regulate expression and secretion of adiponectin, as well regulate the respective receptors in several tissues.

Results
Feeding of a high-fat diet increased serum glucose levels and decreased adiponectin and adipoR2 mRNA expression in subcutaneous and retroperitoneal adipose tissues, respectively. Moreover, it increased both adipoR1 and adipoR2 mRNA levels in muscle and adipoR2 protein levels in liver. Adrenalectomy combined with the synthetic glucocorticoid dexamethasone treatment resulted in increased glucose and insulin levels, decreased serum adiponectin levels, reduced adiponectin mRNA in epididymal adipose tissue, reduction of adipoR2 mRNA by 7-fold in muscle and reduced adipoR1 and adipoR2 protein levels in muscle. Adrenalectomy alone increased adiponectin mRNA expression 3-fold in subcutaneous adipose tissue and reduced adipoR2 mRNA expression 2-fold in liver.

Conclusion
Hyperglycemia as a result of a high-fat diet is associated with an increase in the expression of the adiponectin receptors in muscle. An excess of glucocorticoids, rather than their absence, increase glucose and insulin and decrease adiponectin levels.
Differential patterns of histone acetylation in inflammatory bowel diseases
Authors: Tsaprouni Loukia G , Ito Kazuhiro , Powell Jonathan J , Adcock Ian M , Punchard Neville 
Published: February 2011

Abstract
Post-translational modifications of histones, particularly acetylation, are associated with the regulation of inflammatory gene expression. We used two animal models of inflammation of the bowel and biopsy samples from patients with Crohn's disease (CD) to study the expression of acetylated histones (H) 3 and 4 in inflamed mucosa. Acetylation of histone H4 was significantly elevated in the inflamed mucosa in the trinitrobenzene sulfonic acid model of colitis particularly on lysine residues (K) 8 and 12 in contrast to non-inflamed tissue. In addition, acetylated H4 was localised to inflamed tissue and to Peyer's patches (PP) in dextran sulfate sodium (DSS)-treated rat models. Within the PP, H3 acetylation was detected in the mantle zone whereas H4 acetylation was seen in both the periphery and the germinal centre. Finally, acetylation of H4 was significantly upregulated in inflamed biopsies and PP from patients with CD. Enhanced acetylation of H4K5 and K16 was seen in the PP. These results demonstrate that histone acetylation is associated with inflammation and may provide a novel therapeutic target for mucosal inflammation.
A nanocomplex that is both tumor cell-selective and cancer gene-specific for anaplastic large cell lymphoma
Authors: Zhao Nianxi , Bagaria Hitesh G , Wong Michael S , Zu Youli 
Published: February 2011

AbstractBackgroundManyin vitrostudies have demonstrated that silencing of cancerous genes by siRNAs is a potential therapeutic approach for blocking tumor growth. However, siRNAs are not cell type-selective, cannot specifically target tumor cells, and therefore have limitedin vivoapplication for siRNA-mediated gene therapy.ResultsIn this study, we tested a functional RNA nanocomplex which exclusively targets and affects human anaplastic large cell lymphoma (ALCL) by taking advantage of the abnormal expression of CD30, a unique surface biomarker, and the anaplastic lymphoma kinase (ALK) gene in lymphoma cells. The nanocomplexes were formulated by incorporating both ALK siRNA and a RNA-based CD30 aptamer probe onto nano-sized polyethyleneimine-citrate carriers. To minimize potential cytotoxicity, the individual components of the nanocomplexes were used at sub-cytotoxic concentrations. Dynamic light scattering showed that formed nanocomplexes were ~140 nm in diameter and remained stable for more than 24 hours in culture medium. Cell binding assays revealed that CD30 aptamer probes selectively targeted nanocomplexes to ALCL cells, and confocal fluorescence microscopy confirmed intracellular delivery of the nanocomplex. Cell transfection analysis showed that nanocomplexes silenced genes in an ALCL cell type-selective fashion. Moreover, exposure of ALCL cells to nanocomplexes carrying both ALK siRNAs and CD30 RNA aptamers specifically silenced ALK gene expression, leading to growth arrest and apoptosis.ConclusionsTaken together, our findings indicate that this functional RNA nanocomplex is both tumor cell type-selective and cancer gene-specific for ALCL cells.
Down-regulation of phosphoglucomutase 3 mediates sulforaphane-induced cell death in LNCaP prostate cancer cells
Authors: Lee Chan-Hee , Jeong Soo-Jin , Yun Sun-Mi , Kim Ji-Hyun , Lee Hyo-Jung , Ahn Kwang Seok , Won Suk-Hyun , Kim Hyun Seok , Lee Hyo-Jeong , Ahn Kyoo-Seok , Zhu Shudong , Chen Chang-Yan , Kim Sung-Hoon 
Published: February 2011

Abstract

Background
Sulforaphane (SFN) is an isothiocyanate found in cruciferous vegetables that exerts anti-oxidant, anti-inflammatory, anti-cancer and radio-sensitizing activities. Nonetheless, the mechanism responsible for SFN-induced cell death is not fully understood. In the present study, anti-cancer mechanism of SFN was elucidated in LNCaP prostate cancer cells.

Results
SFN exerted cytotoxicity and increased TUNEL positive cells in a concentration-dependent manner in LNCaP cells. Proteomics study revealed that levels of nine proteins including tubulin β-2, phosphoglucomutase-3 (PGM3), melanoma-derived leucine zipper containing extra-nuclear factor, activin A type I receptor precursor, smoothelin-A, KIA0073, hypothetical protein LOC57691 and two unnamed proteins were changed over 8 folds in SFN treated LNCaP cells compared to untreated control. We have further confirmed that SFN reduced PGM3 expression with western blotting and showed that PGM3 siRNA enhanced cytotoxicity demonstrated by cell morphology and TUNEL assays in LNCaP cells.

Conclusion
Taken together, these findings suggest that PGM3 plays a role in mediating SFN-induced cell death in LNCaP cells, and is a potential molecular therapeutic target for prostate cancer.
Gastrointestinal stromal tumors: correlation between symptoms at presentation, tumor location and prognostic factors in 47 consecutive patients
Authors: Caterino Salvatore , Lorenzon Laura , Petrucciani Niccolò , Iannicelli Elsa , Pilozzi Emanuela , Romiti Adriana , Cavallini Marco , Ziparo Vincenzo 
Published: February 2011

Abstract

Background
Gastrointestinal stromal tumors (GIST) are mesenchymal tumors of the gastrointestinal tract, usually kit-positive, that are believed to originate from interstitial cell of Cajal, or their related stem cells. The most common clinical presentation of these tumors is gastrointestinal bleeding, otherwise they may cause intestinal obstruction, abdominal pain, a palpable mass, or can be incidentally detected during surgery or endoscopic/radiological procedures. Prognosis is related to the size of the tumor and to the mitotic rate; other prognostic factors are tumor location, tumor resection margins, tumor rupture, and c-kit mutation that may interfere with molecular target therapy efficacy.

Aim
Primary aim of this study was to report our experience regarding GIST patients, correlating symptoms at presentation with tumor localization and risk factors.

Patients and methods
47 consecutive patients undergone to surgical resection for GISTs were enrolled in a prospective study from December 1999 to March 2009. Patient's clinical and pathological features were collected and analysed.

Results
The most common symptom was abdominal pain. Bleeding in the digestive tract and abdominal pain were more frequent in gastric GISTs (58% and 61%); acute abdominal symptoms were more frequent in jejunal and ileal GISTs (40% and 60%), p < 0.05. We reported a mild correlation between the mitotic rate index and symptoms at presentation (p 0.074): this correlation was stronger if GISTs causing "acute abdominal symptoms" were compared with GISTs causing "abdominal pain" as main symptom (p 0.039) and with "incidental" GISTs (p 0.022).
We observed an higher prevalence of symptomatic patients in the "high risk/malignant group" of both the Fletcher's and Miettines's classification (p < 0.05).

Conclusion
According with our findings symptoms correlate to tumor location, to class risk criteria as mitotic index and risk classifications, however we cannot conclude that symptoms are per se predictive of survival or patient's outcome.
Impaired desensitization of a human polymorphic α2B-adrenergic receptor variant enhances its sympatho-inhibitory activity in chromaffin cells
Authors: Nguyen Kristy , Kassimatis Theodoros , Lymperopoulos Anastasios 
Published: February 2011

Abstract

Background
α2-adrenergic receptors (ARs) mediate many cellular actions of epinephrine and norepinephrine and inhibit their secretion from adrenal chromaffin cells. Like many other G-protein coupled receptors (GPCRs), they undergo agonist-dependent phopshorylation and desensitization by GPCR Kinases (GRKs), a phenomenon recently shown to play a major role in the sympathetic overdrive that accompanies and aggravates chronic heart failure. A deletion polymorphism in the human α2B-AR gene (Glu301-303) causes impaired agonist-promoted receptor phosphorylation and desensitization in heterologous cell lines. Given the importance of α2-ARs in regulation of catecholamine secretion from chromaffin cells, we sought to investigate, in the present study, the desensitization properties and the sympatho-inhibitory activity of this variant in a chromaffin cell line. For this purpose, we expressed this variant and its wild type counterpart in the well-established chromaffin cell line PC12, and performed receptor phosphorylation and desensitization studies, as well as in vitro catecholamine secretion assays.

Results
Both the agonist-induced phosphorylation and agonist-dependent desensitization of the human Glu301-303 deletion polymorphic α2B-AR are significantly impaired in PC12 cells, resulting in enhanced signaling to inhibition of cholinergic-induced catecholamine secretion in vitro.

Conclusion
This α2B-AR gene polymorphism (Glu301-303 deletion) might confer better protection against conditions characterized and aggravated by sympathetic/catecholaminergic overstimulation in vivo.