bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality of cancer care among foreign‐born and US‐born patients with lung or colorectal cancer
Authors: Nielsen Signe Smith , He Yulei , Ayanian John Z. , Gomez Scarlett Lin , Kahn Katherine L. , West Dee W. , Keating Nancy L.
Published: July 2010

BACKGROUND:

Disparities in care have been documented for foreign‐born cancer patients in the United States. However, few data are available regarding patients with lung and colorectal cancer. In the current study, the authors assessed whether patient‐reported quality and receipt of recommended care differed between US‐born and foreign‐born cancer patients.

METHODS:

The authors collected surveys and medical records for a population‐based cohort including white, Hispanic, and Asian adults (2205 US‐born and 890 foreign‐born individuals) with lung or colorectal cancer diagnosed in California from 2003 through 2005. Logistic regression was used to assess the association between nativity and patient‐reported quality of care and receipt of recommended treatments (adjuvant chemotherapy for stage III colon cancer, adjuvant chemotherapy and radiotherapy for stage II/III rectal cancer, and curative surgery for stage I/II nonsmall cell lung cancer). The authors also assessed whether language explained any differences in care by nativity.

RESULTS:

Overall, 46% of patients reported excellent care, but foreign‐born patients were less likely than US‐born patients to report excellent quality of care (adjusted odds ratio [AOR], 0.80; 95% confidence interval [95% CI], 0.65‐1.00), a difference partly explained by the language of the survey, an indicator of English proficiency. Rates of recommended therapies ranged from 64% to 85%; foreign‐born patients were less likely to receive chemotherapy and radiotherapy for stage II/III rectal cancer (AOR, 0.35; 95% CI, 0.12‐0.99). Rates of other treatments did not differ significantly by nativity.

CONCLUSIONS:

Foreign‐born cancer patients reported lower quality of care and were less likely to receive some cancer therapies than patients born in the Unites States. Better coordination of care and communication regarding cancer treatments and expanded use of interpreters may lessen these disparities. Cancer 2010. © 2010 American Cancer Society.
Steroid hormone regulation of the voltage‐gated, calcium‐activated potassium channel expression in developing muscular and neural systems
Authors: Garrison Sheldon L. , Witten Jane L.
Published: July 2010

A precise organization of gene expression is required for developing neural and muscular systems. Steroid hormones can control the expression of genes that are critical for development. In this study we test the hypothesis that the steroid hormone ecdysone regulates gene expression of the voltage‐gated calcium‐activated potassium ion channel, Slowpoke or KCNMA1. Late in adult development of the tobacco hawkmoth Manduca sexta, slowpoke
(msslo) levels increased contributing to the maturation of the dorsal longitudinal flight muscles (DLMs) and CNS. We show that critical components of ecdysteroid gene regulation were present during upreglation of msslo in late adult DLM and CNS development. Ecdysteroid receptor complex heterodimeric partner proteins, the ecdysteroid receptor (EcR) and ultraspiracle (USP), and the ecdysone‐induced early gene, msE75B, were expressed at key developmental time points, suggesting that ecdysteroids direct aspects of gene expression in the DLMs during these late developmental stages. We provide evidence that ecdysteroids suppress msslo transcription in the DLMs; when titers decline msslo transcript levels increase. These results are consistent with msslo being a downstream gene in an ecdysteroid‐mediated gene cascade during DLM development. We also show that the ecdysteroids regulate msslo transcript levels in the developing CNS. These results will contribute to our understanding of how the spatiotemporal regulation of slowpoke transcription contributes to tailoring cell excitability to the differing physiological and behavioral demands during development. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 70: 884–896, 2010
Synthesis and Electrochemistry of Cyclopentadienyl Ferratricarbollides Substituted by Me and Ph Groups on the Cage Carbon Atoms
Authors: Holub Josef , Bakardjiev Mario , Štíbr Bohumil , Štěpnička Petr , Císařová Ivana
Published: July 2010

Neutral tricarbollide tautomers of general formula 7‐tBuNH‐8,9‐R,R′‐nido‐7,8,9‐C3B8H9 (N1), where R,R′ = substituents on cage carbon atoms = H, Me, and Ph or their combinations, generated a series of very stable, twelve‐vertex ferratricarbollides of general structure [1‐Cp‐12‐tBuNH‐2,4‐R,R′‐closo‐1,2,4,12‐FeC3B8H8] (2, Cp = η5‐C5H5; yields 30–35 %) together with the isomeric complexes [1‐Cp‐10‐tBuNH‐2,4‐R,R′‐closo‐1,2,4,10‐FeC3B8H8] (3; yields 22–26 %) upon heating with [CpFe(CO)2]2 in mesitylene at reflux for 6 h. Individual compounds were isolated and purified by preparative TLC and characterized by conventional 11B and 1H NMR spectroscopy combined with two‐dimensional [11B‐11B]‐COSY and 1H‐{11B(selective)} NMR spectroscopic techniques). The structures of [1‐Cp‐12‐tBuNH‐2,4‐Me2‐1,2,4,12‐FeC3B8H8] (2c) and [1‐Cp‐12‐tBuNH‐2‐Ph‐1,2,4,12‐FeC3B8H9] (2d) were established by single‐crystal X‐ray diffraction analysis. Electrochemical studies revealed that the FeII/FeIII redox potentials are primarily affected by the type of the ferratricarbaborane cage and, to a lesser extent, by the Me and Ph substituents residing on the cage carbon atoms.
When history constrains identity: Expressing the self to others against the backdrop of a problematic past
Authors: Morton Thomas A. , Sonnenberg Stefanie J.
Published: July 2010

Negative histories threaten collective identity. Much research has focussed on how group members strategically defend against such threats. However, within certain groups such defence is difficult—because the group's past actions were unambiguously negative and because these were public and continue to frame relations with outgroups. We explored the consequences of this form of identity constraint on the individual's experience of the self. Two studies varied the salience of the past as German participants expressed their national identity to either an ingroup (German) or outgroup (English) audience. In both studies expressing German identity to an outgroup audience when the past was salient resulted in a more fragmented sense of self and reduced self‐esteem. This effect was mediated through a perceived inability to enact the self. Results are discussed with respect to the power of context to constrain identity expression, and the consequences of this for the self. Copyright © 2010 John Wiley & Sons, Ltd.
Gully, channel and hillslope erosion – an assessment for a traditionally managed catchment
Authors: Hancock G R , Evans K G
Published: July 2010

Understanding landscape features such as gullying and soil erosion is an important issue in the long‐term dynamics and evolution of both natural, agricultural and rehabilitated (i.e. post‐mining) landscapes. Considerable research has been undertaken examining the initiation, movement and overall dynamics of such features. This study reports on a series of 34 gully heads and other erosion features, such as scour holes (five in total), located in channels in a catchment largely undisturbed by European activity in the Northern Territory, Australia over a 5 year period (2002–2007). During this period the erosion features were monitored for their headward advance/retreat, enlargement or in‐filling. The erosion features ranged in depth from 0.2 m to 1.5 m and widths of 0.3 m to 8 m. Hillslope erosion was also monitored using erosion pins. The catchment was subject to a range of rainfall regimes including extreme rainfall and a Category 5 cyclone and also was burnt every second year so that all grass cover was removed according to traditional management practice. The results of this monitoring show that the erosion features have changed little during this 5 year period. A remote sensing assessment found no relationship between erosion feature morphology and hillslope erosion. The monitored gullies heads and scour holes appear to be resilient landscape features, yet have a morphology that suggests they are ready for rapid headward movement and expansion, leading to a destabilisation of the catchment. Hillslope erosion was found to be related to wetness indices derived from a digital elevation model. Significant linkages were found between hillslope erosion and change in erosion feature depth, indicative of a strong hillslope–channel coupling. Copyright © 2010 Commonwealth of Australia
The cholinergic system in mild cognitive impairment and Alzheimer's disease: An in vivo MRI and DTI study
Authors: Teipel Stefan J. , Meindl Thomas , Grinberg Lea , Grothe Michel , Cantero Jose L. , Reiser Maximilian F. , Möller Hans‐Jürgen , Heinsen Helmut , Hampel Harald
Published: July 2010

Few studies have investigated in vivo changes of the cholinergic basal forebrain in Alzheimer's disease (AD) and amnestic mild cognitive impairment (MCI), an at risk stage of AD. Even less is known about alterations of cortical projecting fiber tracts associated with basal forebrain atrophy. In this study, we determined regional atrophy within the basal forebrain in 21 patients with AD and 16 subjects with MCI compared to 20 healthy elderly subjects using deformation‐based morphometry of MRI scans. We assessed effects of basal forebrain atrophy on fiber tracts derived from high‐resolution diffusion tensor imaging (DTI) using tract‐based spatial statistics. We localized significant effects relative to a map of cholinergic nuclei in MRI standard space as determined from a postmortem brain. Patients with AD and MCI subjects showed reduced volumes in basal forebrain areas corresponding to anterior medial and lateral, intermediate and posterior nuclei of the Nucleus basalis of Meynert (NbM) as well as in the diagonal band of Broca nuclei (P < 0.01). Effects in MCI subjects were spatially more restricted than in AD, but occurred at similar locations. The volume of the right antero‐lateral NbM nucleus was correlated with intracortical projecting fiber tract integrity such as the corpus callosum, cingulate, and the superior longitudinal, inferior longitudinal, inferior fronto‐occipital, and uncinate fasciculus (P < 0.05, corrected for multiple comparisons). Our findings suggest that a multimodal MRI‐DTI approach is supportive to determine atrophy of cholinergic nuclei and its effect on intracortical projecting fiber tracts in AD. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.
Overlapping High-Resolution Copy Number Alterations in Cancer Genomes Identified Putative Cancer Genes in Hepatocellular Carcinoma
Authors: Chen Chian-Feng , Hsu En-Chi , Lin Kuen-Tyng , Tu Pang-Hsien , Chang Hung-Wei , Lin Chin-Hui , Chen Yann-Jang , Gu De-Leung , Lin Chi-Hung , Wu Jer-Yuarn , Chen Yuan-Tsong , Hsu Ming-Ta , Jou Yuh-Shan
Published: July 2010

Recurrent cancer genome aberrations are indicators of residing crucial cancer genes. Although recent advances in genomic technologies have led to a global view of cancer genome aberrations, the identification of target genes and biomarkers from the aberrant loci remains difficult. To facilitate searches of cancer genes in human hepatocellular carcinoma (HCC), we established a comprehensive protocol to analyze copy number alterations (CNAs) in cancer genomes using high-density single nucleotide polymorphism arrays with unpaired reference genomes. We identified common HCC genes by overlapping the shared aberrant loci in multiple cell lines with functional validation and clinical implications. A total of 653 amplicons and 57 homozygous deletions (HDs) were revealed in 23 cell lines. To search for novel HCC genes, we overlapped aberrant loci to uncover 6 HDs and 126 amplicons shared by at least two cell lines. We selected two novel genes, fibronectin type III domain containing 3B (

FNDC3B

) at the 3q26.3 overlapped amplicon and solute carrier family 29 member 2 (

SLC29A2

) at the 11q13.2 overlapped amplicon, to investigate their aberrations in HCC tumorigenesis. Aberrant up-regulation of

FNDC3B

and

SLC29A2

occurred in multiple HCC data sets. Knockdown of these genes in amplified cells decreased cell proliferation, anchorage-independent growth, and tumor formation in xenograft models. Importantly, up-regulation of

SLC29A2

in HCC tissues was significantly associated with advanced stages (

P

= 0.0031), vascular invasion (

P

= 0.0353), and poor patient survival (

P

= 0.0325). Overexpression of

FNDC3B

or

SLC29A2

in unamplified HCC cells promoted cell proliferation through activation of the signal transducer and activator of transcription 3 signaling pathway.

Conclusion:

A standardized genome-wide CNA analysis protocol using data from user-generated or public domains normalized with unpaired reference genomes has been established to facilitate high-throughput detection of cancer genes as significant target genes and biomarkers for cancer diagnosis and therapy. (Hepatology 2010)
Raised Hepatic Bile Acid Concentrations During Pregnancy in Mice Are Associated with Reduced Farnesoid X Receptor Function
Authors: Milona Alexandra , Owen Bryn M. , Cobbold Jeremy F. L. , Willemsen Ellen C. L. , Cox Isobel J. , Boudjelal Mohamed , Cairns William , Schoonjans Kristina , Taylor-Robinson Simon D. , Klomp Leo W. J. , Parker Malcolm G. , White Roger , van Mil Saskia W. C. , Williamson Catherine
Published: July 2010

Pregnancy alters bile acid homeostasis and can unmask cholestatic disease in genetically predisposed but otherwise asymptomatic individuals. In this report, we show that normal pregnant mice have raised hepatic bile acid levels in the presence of procholestatic gene expression. The nuclear receptor farnesoid X receptor (FXR) regulates the transcription of the majority of these genes, and we show that both ablation and activation of Fxr prevent the accumulation of hepatic bile acids during pregnancy. These observations suggest that the function of Fxr may be perturbed during gestation. In subsequent

in vitro

experiments, serum from pregnant mice and humans was found to repress expression of the Fxr target gene, small heterodimer partner (

Shp

), in liver-derived Fao cells. Estradiol or estradiol metabolites may contribute to this effect because coincubation with the estrogen receptor (ER) antagonist fulvestrant (ICI 182780) abolished the repressive effects on

Shp

expression. Finally, we report that ERα interacts with FXR in an estradiol-dependent manner and represses its function

in vitro.

Conclusion:

Ligand-activated ERα may inhibit FXR function during pregnancy and result in procholestatic gene expression and raised hepatic bile acid levels. We propose that this could cause intrahepatic cholestasis of pregnancy in genetically predisposed individuals. Hepatology 2010
Visceral Adiposity Index Is Associated with Histological Findings and High Viral Load in Patients with Chronic Hepatitis C Due to Genotype 1
Authors: Petta Salvatore , Amato Marco , Cabibi Daniela , Cammà Calogero , Di Marco Vito , Giordano Carla , Galluzzo Aldo , Craxì Antonio
Published: July 2010

Metabolic factors have been associated with liver damage in patients with genotype 1 chronic hepatitis C (G1 CHC). We tested visceral adiposity index (VAI), a new marker of adipose dysfunction in G1 CHC, patients to assess its association with host and viral factors and its link to both histological findings and sustained virological response (SVR). Two hundred thirty-six consecutive G1 CHC patients were evaluated by way of liver biopsy and anthropometric and metabolic measurements, including insulin resistance (IR), homeostasis model assessment (HOMA), and VAI using waist circumference, body mass index, triglycerides, and high-density lipoprotein cholesterol. All biopsies were scored by one pathologist for staging and grading and graded for steatosis, which was considered moderate to severe if ≥30%. Multiple linear regression analysis revealed that VAI score was independently associated with higher HOMA score (

P

= 0.009), log10 hepatitis C virus RNA levels (

P

= 0.01), necroinflammatory activity (

P

= 0.04), and steatosis (

P

= 0.04). Multiple logistic regression analysis revealed that IR (OR 3.879, 95% CI 1.727-8.713,

P

= 0.001), higher VAI score (OR 1.472, 95% CI 1.051-2.062,

P

= 0.02), and fibrosis (OR 2.255, 95% CI 1.349-3.768,

P

= 0.002) were linked to steatosis ≥30%. Logistic regression analysis revealed that older age (OR 1.030, 95% CI 1.002-1.059,

P

= 0.03), higher VAI score (OR 1.618, 95% CI 1.001-2.617,

P

= 0.04), and fibrosis (OR 2.608, 95% CI 1.565-4.345,

P

< 0.001) were independently associated with moderate to severe necroinflammatory activity. No independent associations were found between VAI score and both fibrosis and SVR.

Conclusion:

In G1 CHC patients, higher VAI score is independently associated with both steatosis and necroinflammatory activity and has a direct correlation with viral load. (Hepatology 2010.)
Activation of LKB1-Akt Pathway Independent of Phosphoinositide 3-Kinase Plays a Critical Role in the Proliferation of Hepatocellular Carcinoma From Nonalcoholic Steatohepatitis
Authors: Martínez-López Nuria , Varela-Rey Marta , Fernández-Ramos David , Woodhoo Ashwin , Vázquez-Chantada Mercedes , Embade Nieves , Espinosa-Hevia Luis , Bustamante Francisco Javier , Parada Luis A. , Rodriguez Manuel S. , Lu Shelly C. , Mato José M. , Martínez-Chantar Maria L.
Published: July 2010

LKB1, originally considered a tumor suppressor, plays an important role in hepatocyte proliferation and liver regeneration. Mice lacking the methionine adenosyltransferase (MAT) gene

MAT1A

exhibit a chronic reduction in hepatic

S

-adenosylmethionine (SAMe) levels, basal activation of LKB1, and spontaneous development of nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). These results are relevant for human health because patients with liver cirrhosis, who are at risk to develop HCC, have a marked reduction in hepatic

MAT1A

expression and SAMe synthesis. In this study, we isolated a cell line (SAMe-deficient [SAMe-D]) from

MAT1A

knockout (MAT1A-KO) mouse HCC to examine the role of LKB1 in the development of liver tumors derived from metabolic disorders. We found that LKB1 is required for cell survival in SAMe-D cells. LKB1 regulates Akt-mediated survival independent of phosphoinositide 3-kinase, adenosine monophosphate protein–activated kinase (AMPK), and mammalian target of rapamycin complex (mTORC2). In addition, LKB1 controls the apoptotic response through phosphorylation and retention of p53 in the cytoplasm and the regulation of herpesvirus-associated ubiquitin-specific protease (HAUSP) and Hu antigen R (HuR) nucleocytoplasmic shuttling. We identified HAUSP as a target of HuR. Finally, we observed cytoplasmic staining of p53 and p-LKB1(Ser428) in a NASH-HCC animal model (from MAT1A-KO mice) and in liver biopsies obtained from human HCC derived from both alcoholic steatohepatitis and NASH.

Conclusion:

The SAMe-D cell line is a relevant model of HCC derived from NASH disease in which LKB1 is the principal conductor of a new regulatory mechanism and could be a practical tool for uncovering new therapeutic strategies. (Hepatology 2010)
Association of Anti-E1E2 Antibodies with Spontaneous Recovery or Sustained Viral Response to Therapy in Patients Infected with Hepatitis C Virus
Authors: Ndongo Ndiémé , Berthillon Pascale , Pradat Pierre , Vieux Claude , Bordes Isabelle , Berby Françoise , Maynard Marianne , Zoulim Fabien , Trépo Christian , Petit Marie-Anne
Published: July 2010

The monoclonal antibody (mAb) D32.10 recognizes a discontinuous epitope encompassing three regions E1 (amino acids 297-306), E2A (amino acids 480-494), and E2B (amino acids 613-621) juxtaposed on the surface of serum-derived hepatitis C virus (HCV) particles (HCVsp). The mAb D32.10 inhibits efficiently and specifically the binding of HCVsp to human hepatocytes. Therefore, we investigated the clinical relevance of anti-E1E2A,B response in the serum of patients infected with HCV. To this end, an enzyme-linked immunosorbent assay (ELISA) using synthetic E1-, E2A-, and E2B-derived peptides was used. The ELISA was validated in terms of sensitivity, specificity, and test efficiency. The detection of the anti-E1E2 D32.10 epitope-binding antibodies during natural HCV infection in more than 300 HCV-positive sera demonstrated significantly (

P

< 0.001) higher prevalence of these antibodies: (1) in patients who spontaneously cured HCV infection (46 of 52, 88.5%) showing high titers (70% ≥ 1/1000) compared to never-treated patients with chronic hepatitis C (7 of 50, 14%) who actively replicated the virus, and (2) in complete responders (20 of 52, 38.5%) who cleared virus following treatment and achieved a sustained viral response compared to nonresponders (4 of 40, 10%). Serum anti-E1E2 antibodies were monitored before, during, and after the current standard-of-care therapy (pegylated interferon plus ribavirin) in responder and nonresponder patients. Optimal cutoff values were assessed by receiver operating characteristic curve analysis. One month prior to therapy initiation, the threshold of 1131 (optical density × 1000) gave 100% and 86% positive and negative predictive values, respectively, for achieving or not achieving a sustained viral response.

Conclusion:

The anti-E1E2 D32.10 epitope-binding antibodies are associated with control of HCV infection and may represent a new relevant prognostic marker in serum. This unique D32.10 mAb may also have immunotherapeutic potential. (Hepatology 2010)
Anti–Tumor Necrosis Factor α Treatment Promotes Apoptosis and Prevents Liver Regeneration in a Transgenic Mouse Model of Chronic Hepatitis C
Authors: Brenndörfer Erwin Daniel , Weiland Malin , Frelin Lars , Derk Emma , Ahlén Gustaf , Jiao Jian , Bode Johannes Georg , Sällberg Matti
Published: July 2010

Tumor necrosis factor α (TNFα) has been implicated in a variety of inflammatory diseases, and anti-TNFα has been shown to improve therapy when added to standard of care in chronic hepatitis C virus (HCV) infection. In addition, patients with chronic HCV have increased serum levels of TNFα and the macrophage-attracting chemokine (C-C motif) ligand 2 (CCL2). A mouse model of chronic HCV with hepatic nonstructural (NS) 3/4A protein expression mimics the human infection through a reduced response to double-stranded RNA and cleavage of the T cell protein tyrosine phosphatase. The mice also display a resistance to TNFα

in vivo.

We therefore analyzed the relationship between NS3/4A and TNFα. Wild-type and NS3/4A-transgenic (Tg) mice were treated with TNFα/D-galactosamine (D-galN), acting through the TNF receptor 1 on hepatocytes and macrophages, or lipopolysaccharide (LPS)/D-galN, acting through Toll-like receptor 4 on sinusoidal endothelial cells, macrophages, and dendritic cells. Mice were analyzed for hepatic signaling, liver damage, TNFα, and CCL2. Similar to HCV-infected humans, NS3/4A-Tg mice displayed elevated basal levels of TNFα and CCL2. Treatment of NS3/4A-Tg mice with TNFα/D-galN or LPS/D-galN led to increased hepatic nuclear factor kappa B (NFκB) activation, increased TNFα and CCL2 levels, decreased apoptosis, and increased hepatocyte regeneration. Importantly, blocking NFκB activation (bortezomib) or administering anti-TNFα (infliximab) 4 hours after LPS/D-galN injection reversed the resistance of NS3/4A-Tg mice to TNFα-induced liver injury.

Conclusion:

Resistance to TNFα seen in NS3/4A-Tg mice is explained by a hepatoprotective effect of NFκB and TNFα. Hence, anti-TNFα agents block these effects and are antiviral by promoting hepatocyte apoptosis and preventing hepatocyte regeneration. (Hepatology 2010;.)
Liver X Receptor α and Farnesoid X Receptor Are Major Transcriptional Regulators of OATP1B1
Authors: Meyer zu Schwabedissen Henriette E. , Böttcher Kerstin , Chaudhry Amarjit , Kroemer Heyo K. , Schuetz Erin G. , Kim Richard B.
Published: July 2010

Organic anion transporting polypeptide 1B1 (OATP1B1) is a liver-enriched transporter involved in the hepatocellular uptake of many endogenous molecules and several structurally divergent drugs in clinical use. Although OATP1B1 coding region polymorphisms are known to make an impact on substrate drug disposition in humans, little is known regarding the mechanisms underlying the transcriptional regulation of this transporter. In this study, we note that messenger RNA (mRNA) expression of OATP1B1 in a large human liver bank exhibited marked interindividual variability that was not associated with coding region polymorphisms. Accordingly, we hypothesized that such variability in expression is reflective of nuclear receptor-mediated transcriptional regulation of this transporter. We tested prototypical ligands for the nuclear receptors pregnane X receptor (PXR), constitutive androstane receptor (CAR), liver X receptor (LXR) α, and farnesoid X receptor (FXR) in a human hepatoma-derived cell line and noted induction of OATP1B1 mRNA when the cells were treated with LXRα or FXR ligands. To confirm a direct role for LXRα and FXR to OATP1B1 expression, we performed detailed promoter analysis and cell-based reporter gene assays resulting in the identification of two functional FXR response elements and one LXRα response element. The direct interaction between nuclear receptors with the identified response elements was assessed using chromatin immunoprecipitation assays. Using isolated primary human hepatocytes, we show that LXRα or FXR agonists, but not PXR or CAR agonists, are capable of OATP1B1 induction.

Conclusion:

We note that OATP1B1 transcriptional regulation is under dual nuclear receptor control through the oxysterol sensing LXRα and the bile acid sensor FXR. Accordingly, the interplay between OATP1B1 and nuclear receptors may play an important and heretofore unrecognized role during cholestasis, drug-induced liver injury, and OATP1B1 induction–related drug interactions. (Hepatology 2010)
Using spatial accessibility to identify polyclinic service gaps and volume of under‐served population in Singapore using Geographic Information System
Authors: Wong Lai Yin , Heng Bee Hoon , Cheah Jason Tiang Seng , Tan Chee Beng
Published: July 2010

Primary care services in Singapore are provided by 18 Government‐funded polyclinics and about 1200 private General Practitioners (GPs). This study aims to examine the spatial accessibility to polyclinics and identify service gaps, and suggest optimal sites using Geographic Information System (GIS) to aid in future planning. A national database containing 3.6 million polyclinic visits in 2006 were geo‐analysed using ArcView GIS. Patients' travel impedance to the nearest polyclinic was computed using DriveTime to identify areas with the lowest spatial accessibility and highest volume of under‐served population. Jurong West and Sembawang were ranked as top areas with poor spatial accessibility to polyclinic services. ArcGIS was used to identify optimal sites with the minimum accumulated distance impedance to this under‐served population. If new facilities were set up at these identified sites, volume of visits by Jurong West and Sembawang patients who could access the nearest polyclinics within 4 km Euclidean distance from their residence would total at 123 000 and 93 000, respectively. Future efforts in polyclinic planning should take this into consideration to maximize patients' benefits and minimize patients' travelling costs in order to achieve social equity on healthcare access. Copyright © 2010 John Wiley & Sons, Ltd.
Bis‐Aniline‐Crosslinked Enzyme–Metal Nanoparticle Composites on Electrodes for Bioelectronic Applications
Authors: Tel‐Vered Ran , Willner Itamar
Published: July 2010

The electrical contacting of redox enzymes with electrodes is the most fundamental requirement for the development of amperometric biosensors and biofuel cell elements. We describe a novel method to prepare electrically contacted metallic nanoparticles (NPs) or carbon nanotubes (CNTs)/enzyme hybrid composites on electrodes that act as amperometric biosensors or as the constituents of biofuel cells.

Au NPs or Pt NPs were modified with thioaniline electropolymerizable groups, and so were the enzymes glucose oxidase (GOx) or bilirubin oxidase (BOD). Electrochemical polymerization of the thioaniline‐functionalized Pt NPs and GOx on a thioaniline monolayer‐modified Au surface led to the formation of a bis‐aniline‐bridged Pt NPs/GOx composite electrode that enabled the analysis of glucose through the electrocatalyzed reduction of H2O2. Similarly, a Pt NPs/BOD composite‐functionalized electrode showed electrocatalytic activity toward the reduction of O2 to H2O. Also, a Au NPs/GOx composite‐functionalized electrode revealed direct electrical contacting between the enzyme and the electrode through the electrocatalytic reduction of the bis‐aniline bridges, and this enabled the bioelectrocatalytic oxidation and the amperometric sensing of glucose. Finally, a biofuel cell consisting of an anode modified with Nile blue/NAD+/alcohol dehydrogenase on carbon nanotubes, and a cathode composed of the bis‐aniline‐crosslinked Pt NPs/BOD composite was constructed. The biofuel cell operates with a power output corresponding to 200 μW cm‐2.
Expression, localization, and regulation of the neuregulin receptor ErbB3 in mouse heart
Authors: Campreciós Genís , Lorita Jordi , Pardina Eva , Peinado‐Onsurbe Julia , Soley Maria , Ramírez Ignasi
Published: July 2010

Neuregulins (NRG) belong to the EGF family of growth factors, which are ligands of the ErbB receptors. Their expression in the adult heart is essential, especially when the heart is submitted to cardiotoxic stress such as that produced by anthracyclines. It is considered that ErbB4 is the only NRG receptor expressed by the adult heart. Upon binding, ErbB4 may dimerize with ErbB2 to generate signals inside cells. However, here we show the presence of ErbB3 in the mouse heart from birth to adulthood by Western blotting and real‐time RT‐PCR. The expression level of ErbB3 mRNA was lower than that of ErbB2 or ErbB4, but was more stable throughout postnatal development. In isolated heart myocytes, ErbB3 localized to the Z‐lines similarly to ErbB1. Perfusion of isolated hearts with NRG‐1β induced phosphorylation of ErbB3, as well as ErbB2 and ErbB4. In adult mice, both ErbB2 and ErbB3, but not ErbB1 or ErbB4, were rapidly down‐regulated upon the induction of heart hypertrophy. In conclusion, our results demonstrate that ErbB3, in addition to ErbB4, is a receptor for neuregulin‐1β in the adult mouse heart. J. Cell. Physiol. 226: 450–455, 2011. © 2010 Wiley‐Liss, Inc.
αVβ3 integrin regulates macrophage inflammatory responses via PI3 kinase/Akt‐dependent NF‐κB activation
Authors: Antonov Alexander S. , Antonova Galina N. , Munn David H. , Mivechi Nahid , Lucas Rudolf , Catravas John D. , Verin Alexander D.
Published: July 2010

Controlling macrophage responses to pathogenic stimuli is critical for prevention of and recovery from the inflammatory state associated with the pathogenesis of many diseases. The adhesion receptor αVβ3 integrin is thought to be an important receptor that regulates macrophage differentiation and macrophage responses to external signaling, but it has not been previously identified as a contributor to macrophage‐related inflammation. Using an in vitro model of human blood monocytes (Mo) and monocyte‐derived macrophages (MDMs) we demonstrate that αVβ3 ligation results in sustained increases of the transcription factor NF‐κB DNA‐binding activity, as compared with control isotype‐matched IgG1. Activation of NF‐κB parallels the increase of NF‐κB‐dependent pro‐inflammatory cytokine mRNA expression in MDMs isolated from individual donors, for example, TNF‐α (8‐ to 28‐fold), IL‐1β (15‐ to 30‐fold), IL‐6 (2‐ to 4‐fold), and IL‐8 (5‐ to 15‐fold) whereas there is more than a 10‐fold decrease in IL‐10 mRNA level occurs. Upon ligation of the αVβ3 receptor, treatment with TNF‐α (10 ng/ml) or LPS (200 ng/ml, 1,000 EU) results in the enhanced and synergistic activation of NF‐κB and LPS‐induced TNF‐α secretion. As additional controls, an inhibitor of αVβ3 integrin, cyclic RGD (10 µg/ml; IC50 = 7.6 µM), attenuates the effects of αVβ3 ligation, and the natural ligand of αVβ3 integrin, vitronectin, reproduces the effects of αVβ3 activation by an immobilizing anti‐αVβ3 integrin mAb. We hypothesize that αVβ3 activation can maintain chronic inflammatory processes in pathological conditions and that the loss of αVβ3 ligation will allow macrophages to escape from the inflammatory state. J. Cell. Physiol. 226: 469–476, 2011. © 2010 Wiley‐Liss, Inc.
Influence of pH on recombinant human growth hormone production by Pichia pastoris
Authors: Çalık Pınar , Bayraktar Eda , İnankur Bahar , Soyaslan Elif Ş. , Şahin Merve , Taşpınar Hatice , Açık Eda , Yılmaz Remziye , Özdamar Tunçer H.
Published: July 2010

BACKGROUND: Effect of pH on recombinant human growth hormone (rhGH) production by Pichia pastoris hGH‐Mut+ was investigated at pH = 4.2, 5.0, 5.5, and 6.0.

RESULTS: The highest cell concentration was obtained at pH = 6.0 with 53 g L−1, while the highest rhGH concentration was attained at pH = 5.0 as 0.27 g L−1. Total protease secretion increased with increase in pH and with the cultivation time. Oxygen uptake rate increased with increasing pH up to pH = 6.0, having the maximum value, 37 mmol m−3 s−1, at pH = 5.5. KLa values were similar at all the conditions, having a maximum value of 0.14 s−1 at pH = 5.0. Taking the final rhGH concentration into account, the most favourable pH was 5.0; where AOX1 expression level showed a similar trend to AOX activity profiles, having the highest value of 9.4 × 1010 copy mg−1 CDW at t = 15 h; in parallel to AOX1 expression profile, hGH expression level increased until t = 15 h, with the highest value of 4.0 × 1010 copy mg−1 CDW, where a sharp increase in rhGH concentration was obtained. The expression levels of pep4, prb1 and prc1 genes, responsible from the production of proteinase A, proteinase B and, carboxypeptidase Y, were parallel to each other.

CONCLUSION: Since it was shown that pH is a crucial operating parameter in fermentation processes using P. pastoris, keeping pH constant at its determined optimum value, pH = 5.0, during the bioprocess is vital in terms of recombinant protein production. Copyright © 2010 Society of Chemical Industry
LOCALISING THE GLOBAL, GLOBALISING THE LOCAL: THE ROLE OF THE INTERNET IN SHAPING GLOBALISATION DISCOURSE IN INDONESIAN NGOs
Authors: Nugroho Yanuar
Published: July 2010

Globalisation arguably brings about socio‐economic development but the distribution of these benefits is unequal. Non‐governmental organisations (NGOs), whose growth has often been closely linked with globalisation, have been outspoken regarding this inequality. Despite clear linkages between NGOs and globalisation, there has been little research aiming at understanding how NGOs engage with the issue of globalisation itself. Using the case of Indonesia, this study aims to uncover how NGOs utilise the Internet to respond to globalisation‐related issues. NGOs should understand global issues in their local contexts and rearticulate more saliently for their beneficiaries. Technology can serve this purpose when used strategically. Copyright © 2010 John Wiley & Sons, Ltd.
‘Diffuse skin browning’ in 1‐MCP‐treated apples: etiology and systems of control
Authors: Larrigaudière Christian , Vilaplana Rosa , Recasens Inmaculada , Soria Yolanda , Dupille Eve
Published: July 2010

BACKGROUND: ‘Diffuse skin browning’ (DSB) is a physiological disorder that affects Golden Delicious apples treated with 1‐methylcyclopropene (1‐MCP). Although a very high incidence is found, very little is known about the etiology of this disorder. This study aims to provide an understanding of the causes of this disorder and prevent it.

RESULTS: A very high incidence of DSB was found in 1‐MCP‐treated apples independent of the location of the orchard. Similar to superficial scald, harvest maturity determines the DSB incidence, with the more mature fruit being less sensitive. The 1‐MCP dose (156 nL L−1 or 625 nL L−1) and the temperature at which the 1‐MCP treatment was applied (0.5 or 20 °C) did not affect the incidence of DSB. Diphenylamine (DPA) treatment did not prevent DSB, contrary to superficial scald. Additionally, controlled atmosphere storage only partially reduced the incidence of DSB, whereas progressive cooling strategies completely inhibited DSB occurrence. A direct correlation was found between the sensitivity of the Golden Delicious clone to russeting and its sensitivity to develop DSB during storage.

CONCLUSION: Our results indicated that DSB and superficial scald are two different disorders involving different oxidative processes. DSB can be prevented by progressive cooling and selection of russeting‐resistant clones. Copyright © 2010 Society of Chemical Industry
Variation in saponin content during the growing season of spotted medic [Medicago arabica (L.) Huds.]
Authors: Pecetti Luciano , Biazzi Elisa , Tava Aldo
Published: July 2010

BACKGROUND: Spotted medic [Medicago arabica (L.) Huds.] is a minor forage species containing saponins which are reported to be biologically active. This study assessed the concentration and composition pattern of spotted medic saponins during the growing season and at senescence. The pattern of saponins was based on identification and quantification of their constituent sapogenins. At senescence, individual saponin concentrations of aerial and subterranean plant organs were also determined.

RESULTS: Leaf total saponin content did not vary during the growing season and decreased remarkably at senescence. Seven sapogenins were identified and quantified during the season, bayogenin and hederagenin being the most abundant ones throughout. Total saponin content varied among plant organs at senescence, with the highest concentration in roots. A variable number of saponins from one (in seeds) to 19 (in leaves) were quantified. A clear relationship between leaf concentrations of sapogenins and those of their derivative saponins was revealed by correlation analysis.

CONCLUSION: The species displayed a sapogenins/saponins pattern markedly different from those of other perennial or annual Medicago species. Saponins of queretaroic acid and 2β‐hydroxy queretaroic acid had no precedent in the Leguminosae. The high concentration of biologically active hederagenin suggested further assessment of possible effects on feeding animals. Copyright © 2010 Society of Chemical Industry
Albedo hydrolysis modelling and digestion with reused effluents in the enzymatic peeling process of grapefruits
Authors: Pagán Axel , Conde Josep , Ibarz Albert , Pagán Jordi
Published: July 2010

BACKGROUND: Until now, the optimisation of enzymatic peeling of grapefruit in the reactor has been obtained as the result of the semi‐qualitative effects of enzyme activity. This work is an attempt to obtain quantified data. The reuse of enzymes to reduce costs in this process is unprecedented in the literature and is the aim of the present work.

RESULTS: The optimal conditions determined for the maximum albedo degradation were a temperature of 40.6 °C and a time of 13.1 min in an enzymatic concentration of 0.067 mL enzymatic preparation per gram of peel in each litre of citrate buffer solution. The decrease in relative enzymatic activities in reused effluents was determined, as was the increase in activity when the enzymes were purified. These increases were 15.5% for polygalacturonase and 15.4% for cellulase activity.

CONCLUSION: Optimal temperature, time and the ratio between peel mass and the enzymatic preparation volume were the best conditions for obtaining good peeling efficiency. The effluents from the enzymatic peeling process of the grapefruit still contain appreciable enzymatic activity after the digestion process. Thus, reusing these effluents while maintaining peeling efficacy and a subsequent recovery of the active enzymes by ultra‐filtration of the effluents is the way to improve the efficiency of the process. Copyright © 2010 Society of Chemical Industry
Biochemical characterization of a bacteriocin‐like inhibitory substance produced by Enterococcus faecium MXVK29, isolated from Mexican traditional sausage
Authors: Alvarez‐Cisneros Yenizey M , Fernández Francisco J , Wacher‐Rodarte Carmen , Aguilar Manuel B , Sáinz Espuñes Teresita del Rosario , Ponce‐Alquicira Edith
Published: July 2010

BACKGROUND: Enterococci are lactic acid bacteria that can produce bacteriocins, which may offer an additional hurdle to control the growth of food‐borne pathogens; moreover, these bacteriocins may have great potential as natural biopreservatives. The aim of this work was to characterize a bacteriocin‐like inhibitory substance (BLIS) with antilisterial activity produced by an enterococcal strain.

RESULTS: The bacteriogenic strain was isolated from Mexican fermented sausages and identified as Enterococcus faecium with 99% sequence similarity. Maximal activity was detected at 16 h, where bacterial growth was in middle of the stationary phase. The producer strain was not inhibited by its own antimicrobial peptide. BLIS showed a strong anti‐Listeria activity and was inactivated by proteinase K. Heating (121 °C for 15 min) induced some inactivation, but thermotolerance was higher at acid pH values. The yield obtained with a pH‐mediated purification process was 32.7%, showing a band with an estimated molecular weight of 3.5 kDa. Automated N‐terminal Edman degradation showed the following sequence: YYGNGVTCGSHHCSVD.

CONCLUSION: Biochemical characteristics of BLIS produced by E. faecium MXVK29 suggested that it belongs to Class IIa of the Klaenhammer classification and could be considered as a natural food preservative, although further studies need to be performed. Copyright © 2010 Society of Chemical Industry
Influence of glutathione‐S‐transferase theta (GSTT1) and mu (GSTM1) gene polymorphisms on the susceptibility of hepatocellular carcinoma in Taiwan
Authors: Kao Chia‐Chun , Chen Mu‐Kuan , Kuo Wu‐Hsien , Chen Tzy‐Yen , Su Shih‐Chi , Hsieh Yi‐Hsien , Liu Chuen‐Lan , Chou Ming‐Chih , Tsai Hsiu‐Ting , Yang Shun‐Fa
Published: July 2010

Background and Objectives

Hepatocellular carcinoma (HCC) is one of the most frequent malignant neoplasms worldwide and is the second leading cause of cancer death in Taiwan. Genetic polymorphism has been reported as a factor for increased susceptibility of HCC. Glutathione‐S‐transferases theta (GSTT1) and mu (GSTM1) play essential roles in detoxification of ingested xenobiotics and modulation of the susceptibility of gene‐related cancer. The aim of this study was to estimate the relationships between these two gene polymorphisms and HCC risk and clinicopathological status in Taiwanese.

Methods

Polymerase chain reaction (PCR) was used to determine gene polymorphisms of 102 patients with HCC and 386 healthy controls.

Results

Both gene polymorphisms were not associated with the clinical pathological status of HCC and serum levels of liver‐related clinical pathological markers. While no relationship between GSTM1 gene polymorphism and HCC susceptibility was found, individuals of age <56 years old with GSTT1 present genotype have a risk of 2.77‐fold (95% CI: 1.09–7.09) for HCC compared to that with null variant, after adjustment for other confounders.

Conclusions

GSTT1 and GSTM1 null genotypes do not associate with increased risk of HCC. J. Surg. Oncol. 2010;102:301–307. © 2010 Wiley‐Liss, Inc.
Preoperative dietary restriction reduces hepatic tumor load by reduced E‐selectin‐mediated adhesion in mice
Authors: van Ginhoven Tessa M. , van den Berg Jan Willem , Dik Willem A. , IJzermans Jan N.M. , de Bruin Ron W.F.
Published: July 2010

Background

Inflammatory responses facilitate metastasis by increasing expression of adhesion molecules. Dietary restriction (30% reduction in daily calorie intake) reduces the expression of adhesion molecules and protects against surgically induced inflammation. DR might therefore beneficially interfere with surgery‐induced inflammation and subsequent adhesion of circulating tumor cells.

Methods

BALB/c mice were subjected to 2 weeks dietary restriction prior to inoculation with tumor cells. Intra‐splenic injection of 5.0 × 104 C26‐colon carcinoma cells was followed by splenectomy. Hepatic tumor load was scored after 10 days as a percentage (tumor surface/total liver surface) on H&E stained sections. Liver mRNA expression of adhesion molecules was determined and the effect of serum from dietary restriction mice on in vitro tumor growth and adhesion capacity was assessed.

Results

Preoperative dietary restriction significantly reduced mRNA expression levels of E‐selectin (P = 0.0087) and hepatic tumor load (P = 0.036). Dietary restriction serum did not affect in vitro cell growth but reduced in vitro adhesion of C26 cells to endothelial cells (P = 0.0043).

Conclusions

Preoperative dietary restriction reduces hepatic tumor load after injection with tumor cells. Reduced adhesion to endothelial cells and reduced mRNA expression of E‐selectin suggest that dietary restriction reduces tumor load by lowering the adhesion of circulating tumor cells to hepatic vascular endothelium. J. Surg. Oncol. 2010;102:348–353. © 2010 Wiley‐Liss, Inc.
LRRK2 variation and Parkinson's disease in African Americans
Authors: Ross Owen A. , Wilhoite Greggory J. , Bacon Justin A. , Soto‐Ortolaza Alexandra , Kachergus Jennifer , Cobb Stephanie A. , Puschmann Andreas , Vilariño‐Güell Carles , Farrer Matthew J. , Graff‐Radford Neill , Meschia James F. , Wszolek Zbigniew K.
Published: July 2010

The global impact of LRRK2 mutations is yet to be realized with a lack of studies in specific ethnic groups, including those of Asian and African descent. Herein, we investigated the frequency of common LRRK2 variants by complete exon sequencing in a series of publicly available African American Parkinson's disease patients. Our study identified three novel synonymous exonic variants and 13 known coding variations; however, there did not appear to be any frequent (>5%) pathogenic mutations. Given the ethnic‐specific LRRK2 variation previously identified in PD further studies in under‐represented populations are warranted. © 2010 Movement Disorder Society.
Thomas de Quincey and his restless legs symptoms as depicted in “Confessions of an English Opium‐Eater”
Authors: Miranda Marcelo , Williams Anne‐Marie , Garcia‐Borreguero Diego
Published: July 2010

Thomas de Quincey, a British writer of 19th century, suffered insomnia from the age of 17 years. In his famous “Confessions of an English‐Opium Eater” (1822), he described a symptomatology that could concord with restless legs syndrome long before he became addicted to opium. In this report, we analyze his clinical description and the circumstances leading to his opium addiction. © 2010 Movement Disorder Society