bluuebunny/crossref_metadata_2025 huggingface dataset:
Upregulation of soluble epoxide hydrolase in proximal tubular cells mediated proteinuria-induced renal damage
Authors: Wang Qian , Pang Wei , Cui Zhuan , Shi Junbao , Liu Yan , Liu Bo , Zhou Yunfeng , Guan Youfei , Hammock Bruce D. , Wang Yue , Zhu Yi
Published: November 2012

Epoxyeicosatrienoic acids, hydrolyzed by soluble epoxide hydrolase (sEH), have multiple biological functions, including the regulation of vascular tone, renal tubular transport, and being anti-inflammatory. Inhibitors of sEH have been demonstrated to be antihypertensive and renal protective. To elucidate the role of sEH in glomerulonephritis, we first determined the expression of sEH in human kidney by examining biopsies from 153 patients with a variety of glomerulonephritis, including minimal-change, membranous, and IgA nephropathy. Immunohistochemical staining of frozen kidney biopsy samples revealed sEH preferentially expressed in the renal proximal tubular cells, and its expression increased in all patients with glomerulonephritis. The level of sEH in the cortex was positively correlated with proteinuria and negatively with serum albumin level. To investigate the role of sEH in proteinuria-induced renal damage, we incubated purified urine protein from patients with rat renal proximal tubular epithelial cells in vitro. The level of sEH was elevated, as were monocyte chemoattractant protein 1 and the process of tubular epithelial-to-mesenchymal transition, characterized with increased α-smooth muscle actin (α-SMA) and decreased E-cadherin. These effects were attenuated by administration of a potent sEH inhibitor and mimicked with adenovirus-mediated sEH overexpression. In adriamycin-induced nephropathic mice, sEH inhibitor did not ameliorate proteinuria or level of serum albumin but reduced the long-term elevated serum creatinine level, interstitial inflammation, fibrosis, and α-SMA expression. Thus upregulation of sEH in proximal tubular cells in chronic proteinuric kidney diseases may mediate proteinuria-induced renal damage; sEH inhibition by increasing renal eicosanoid levels could prevent the progression of chronic proteinuric kidney diseases.
Effects of acute selective pudendal nerve electrical stimulation after simulated childbirth injury
Authors: Jiang Hai-Hong , Gill Bradley C. , Dissaranan Charuspong , Zutshi Massarat , Balog Brian M. , Lin Danli , Damaser Margot S.
Published: November 2012

During childbirth, a combinatorial injury occurs and can result in stress urinary incontinence (SUI). Simulated childbirth injury, consisting of vaginal distension (VD) and pudendal nerve crush (PNC), results in slowed recovery of continence, as well as decreased expression of brain-derived neurotrophic factor (BDNF), a regenerative cytokine. Electrical stimulation has been shown to upregulate BDNF in motor neurons and facilitate axon regrowth through the increase of βII-tubulin expression after injury. In this study, female rats underwent selective pudendal nerve motor branch (PNMB) stimulation after simulated childbirth injury or sham injury to determine whether such stimulation affects bladder and anal function after injury and whether the stimulation increases BDNF expression in Onuf's nucleus after injury. Rats received 4 h of VD followed by bilateral PNC and 1 h of subthreshold electrical stimulation of the left PNMB and sham stimulation of the right PNMB. Rats underwent filling cystometry and anal pressure recording before, during, and after the stimulation. Bladder and anal contractile function were partially disrupted after injury. PNMB stimulation temporarily inhibited bladder contraction after injury. Two days and 1 wk after injury, BDNF expression in Onuf's nucleus of the stimulated side was significantly increased compared with the sham-stimulated side, whereas βII-tubulin expression in Onuf's nucleus of the stimulated side was significantly increased only 1 wk after injury. Acute electrical stimulation of the pudendal nerve proximal to the crush site upregulates BDNF and βII-tubulin in Onuf's nucleus after simulated childbirth injury, which could be a potential preventive option for SUI after childbirth injury.
Calcium reabsorption in the distal tubule: regulation by sodium, pH, and flow
Authors: Bonny Olivier , Edwards Aurélie
Published: November 2012

We developed a mathematical model of Ca2+transport along the late distal convoluted tubule (DCT2) and the connecting tubule (CNT) to investigate the mechanisms that regulate Ca2+reabsorption in the DCT2-CNT. The model accounts for apical Ca2+influx across transient receptor potential vanilloid 5 (TRPV5) channels and basolateral Ca2+efflux via plasma membrane Ca2+-ATPase pumps and type 1 Na+/Ca2+exchangers (NCX1). Model simulations reproduce experimentally observed variations in Ca2+uptake as a function of extracellular pH, Na+, and Mg2+concentration. Our results indicate that amiloride enhances Ca2+reabsorption in the DCT2-CNT predominantly by increasing the driving force across NCX1, thereby stimulating Ca2+efflux. They also suggest that because aldosterone upregulates both apical and basolateral Na+transport pathways, it has a lesser impact on Ca2+reabsorption than amiloride. Conversely, the model predicts that full NCX1 inhibition and parathyroidectomy each augment the Ca2+load delivered to the collecting duct severalfold. In addition, our results suggest that regulation of TRPV5 activity by luminal pH has a small impact, per se, on transepithelial Ca2+fluxes; the reduction in Ca2+reabsorption induced by metabolic acidosis likely stems from decreases in TRPV5 expression. In contrast, elevations in luminal Ca2+are predicted to significantly decrease TRPV5 activity via the Ca2+-sensing receptor. Nevertheless, following the administration of furosemide, the calcium-sensing receptor-mediated increase in Ca2+reabsorption in the DCT2-CNT is calculated to be insufficient to prevent hypercalciuria. Altogether, our model predicts complex interactions between calcium and sodium reabsorption in the DCT2-CNT.
Local inhibition modulates learning-dependent song encoding in the songbird auditory cortex
Authors: Thompson Jason V. , Jeanne James M. , Gentner Timothy Q.
Published: November 2012

Changes in inhibition during development are well documented, but the role of inhibition in adult learning-related plasticity is not understood. In songbirds, vocal recognition learning alters the neural representation of songs across the auditory forebrain, including the caudomedial nidopallium (NCM), a region analogous to mammalian secondary auditory cortices. Here, we block local inhibition with the iontophoretic application of gabazine, while simultaneously measuring song-evoked spiking activity in NCM of European starlings trained to recognize sets of conspecific songs. We find that local inhibition differentially suppresses the responses to learned and unfamiliar songs and enhances spike-rate differences between learned categories of songs. These learning-dependent response patterns emerge, in part, through inhibitory modulation of selectivity for song components and the masking of responses to specific acoustic features without altering spectrotemporal tuning. The results describe a novel form of inhibitory modulation of the encoding of learned categories and demonstrate that inhibition plays a central role in shaping the responses of neurons to learned, natural signals.
De Novo Design of a Tumor-Penetrating Peptide
Authors: Alberici Luca , Roth Lise , Sugahara Kazuki N. , Agemy Lilach , Kotamraju Venkata R. , Teesalu Tambet , Bordignon Claudio , Traversari Catia , Rizzardi Gian-Paolo , Ruoslahti Erkki
Published: November 2012

Poor penetration of antitumor drugs into the extravascular tumor tissue is often a major factor limiting the efficacy of cancer treatments. Our group has recently described a strategy to enhance tumor penetration of chemotherapeutic drugs through use of iRGD peptide (CRGDK/RGPDC). This peptide comprises two sequence motifs: RGD, which binds to αvβ3/5 integrins on tumor endothelia and tumor cells, and a cryptic CendR motif (R/KXXR/K-OH). Once integrin binding has brought iRGD to the tumor, the peptide is proteolytically cleaved to expose the cryptic CendR motif. The truncated peptide loses affinity for its primary receptor and binds to neuropilin-1, activating a tissue penetration pathway that delivers the peptide along with attached or co-administered payload into the tumor mass. Here, we describe the design of a new tumor-penetrating peptide based on the current knowledge of homing sequences and internalizing receptors. The tumor-homing motif in the new peptide is the NGR sequence, which binds to endothelial CD13. The NGR sequence was placed in the context of a CendR motif (RNGR), and this sequence was embedded in the iRGD framework. The resulting peptide (CRNGRGPDC, iNGR) homed to tumor vessels and penetrated into tumor tissue more effectively than the standard NGR peptide. iNGR induced greater tumor penetration of coupled nanoparticles and co-administered compounds than NGR. Doxorubicin given together with iNGR was significantly more efficacious than the drug alone. These results show that a tumor-specific, tissue-penetrating peptide can be constructed from known sequence elements. This principle may be useful in designing tissue-penetrating peptides for other diseases. Cancer Res; 73(2); 804–12. ©2012 AACR.
A Candidate Molecular Biomarker Panel for the Detection of Bladder Cancer
Authors: Urquidi Virginia , Goodison Steve , Cai Yunpeng , Sun Yijun , Rosser Charles J.
Published: November 2012

Background: Bladder cancer is among the five most common malignancies worldwide, and due to high rates of recurrence, one of the most prevalent. Improvements in noninvasive urine-based assays to detect bladder cancer would benefit both patients and health care systems. In this study, the goal was to identify urothelial cell transcriptomic signatures associated with bladder cancer.

Methods: Gene expression profiling (Affymetrix U133 Plus 2.0 arrays) was applied to exfoliated urothelia obtained from a cohort of 92 subjects with known bladder disease status. Computational analyses identified candidate biomarkers of bladder cancer and an optimal predictive model was derived. Selected targets from the profiling analyses were monitored in an independent cohort of 81 subjects using quantitative real-time PCR (RT-PCR).

Results: Transcriptome profiling data analysis identified 52 genes associated with bladder cancer (P ≤ 0.001) and gene models that optimally predicted class label were derived. RT-PCR analysis of 48 selected targets in an independent cohort identified a 14-gene diagnostic signature that predicted the presence of bladder cancer with high accuracy.

Conclusions: Exfoliated urothelia sampling provides a robust analyte for the evaluation of patients with suspected bladder cancer. The refinement and validation of the multigene urothelial cell signatures identified in this preliminary study may lead to accurate, noninvasive assays for the detection of bladder cancer.

Impact: The development of an accurate, noninvasive bladder cancer detection assay would benefit both the patient and health care systems through better detection, monitoring, and control of disease. Cancer Epidemiol Biomarkers Prev; 21(12); 2149–58. ©2012 AACR.
A Randomized Controlled Trial of a Tailored Navigation and a Standard Intervention in Colorectal Cancer Screening
Authors: Myers Ronald E. , Bittner-Fagan Heather , Daskalakis Constantine , Sifri Randa , Vernon Sally W. , Cocroft James , DiCarlo Melissa , Katurakes Nora , Andrel Jocelyn
Published: November 2012

Background: This randomized, controlled trial assessed the impact of a tailored navigation intervention versus a standard mailed intervention on colorectal cancer screening adherence and screening decision stage (SDS).

Methods: Primary care patients (n = 945) were surveyed and randomized to a Tailored Navigation Intervention (TNI) Group (n = 312), Standard Intervention (SI) Group (n = 316), or usual care Control Group (n = 317). TNI Group participants were sent colonoscopy instructions and/or stool blood tests according to reported test preference, and received a navigation call. The SI Group was sent both colonoscopy instructions and stool blood tests. Multivariable analyses assessed intervention impact on adherence and change in SDS at 6 months.

Results: The primary outcome, screening adherence (TNI Group: 38%, SI Group: 33%, Control Group: 12%), was higher for intervention recipients than controls (P = 0.001 and P = 0.001, respectively), but the two intervention groups did not differ significantly (P = 0.201). Positive SDS change (TNI Group: +45%, SI Group: +37%, and Control Group: +23%) was significantly greater among intervention recipients than controls (P = 0.001 and P = 0.001, respectively), and the intervention group difference approached significance (P = 0.053). Secondary analyses indicate that tailored navigation boosted preferred test use, and suggest that intervention impact on adherence and SDS was attenuated by limited access to screening options.

Conclusions: Both interventions had significant, positive effects on outcomes compared with usual care. TNI versus SI impact had a modest positive impact on adherence and a pronounced effect on SDS.

Impact: Mailed screening tests can boost adherence. Research is needed to determine how preference, access, and navigation affect screening outcomes. Cancer Epidemiol Biomarkers Prev; 22(1); 109–17. ©2012 AACR.
A Variable Age of Onset Segregation Model for Linkage Analysis, with Correction for Ascertainment, Applied to Glioma
Authors: Sun Xiangqing , Vengoechea Jaime , Elston Robert , Chen Yanwen , Amos Christopher I. , Armstrong Georgina , Bernstein Jonine L. , Claus Elizabeth , Davis Faith , Houlston Richard S. , Il'yasova Dora , Jenkins Robert B. , Johansen Christoffer , Lai Rose , Lau Ching C. , Liu Yanhong , McCarthy Bridget J. , Olson Sara H. , Sadetzki Siegal , Schildkraut Joellen , Shete Sanjay , Yu Robert , Vick Nicholas A. , Merrell Ryan , Wrensch Margaret , Yang Ping , Melin Beatrice , Bondy Melissa L. , Barnholtz-Sloan Jill S. ,   on behalf of the Gliogene Consortium
Published: November 2012

Background: We propose a 2-step model-based approach, with correction for ascertainment, to linkage analysis of a binary trait with variable age of onset and apply it to a set of multiplex pedigrees segregating for adult glioma.

Methods: First, we fit segregation models by formulating the likelihood for a person to have a bivariate phenotype, affection status and age of onset, along with other covariates, and from these we estimate population trait allele frequencies and penetrance parameters as a function of age (N = 281 multiplex glioma pedigrees). Second, the best fitting models are used as trait models in multipoint linkage analysis (N = 74 informative multiplex glioma pedigrees). To correct for ascertainment, a prevalence constraint is used in the likelihood of the segregation models for all 281 pedigrees. Then the trait allele frequencies are reestimated for the pedigree founders of the subset of 74 pedigrees chosen for linkage analysis.

Results: Using the best-fitting segregation models in model-based multipoint linkage analysis, we identified 2 separate peaks on chromosome 17; the first agreed with a region identified by Shete and colleagues who used model-free affected-only linkage analysis, but with a narrowed peak: and the second agreed with a second region they found but had a larger maximum log of the odds (LOD).

Conclusions: Our approach was able to narrow the linkage peak previously published for glioma.

Impact: We provide a practical solution to model-based linkage analysis for disease affection status with variable age of onset for the kinds of pedigree data often collected for linkage analysis. Cancer Epidemiol Biomarkers Prev; 21(12); 2242–51. ©2012 AACR.
Exposure to Heavy Metals and Polycyclic Aromatic Hydrocarbons and DNA Damage in Taiwanese Traffic Conductors
Authors: Huang Han-Bin , Chen Guan-Wen , Wang Chien-Jen , Lin Yong-Yang , Liou Saou-Hsing , Lai Ching-Huang , Wang Shu-Li
Published: November 2012

Background: Exposure to traffic-related air pollutants, including polycyclic aromatic hydrocarbons (PAH) and heavy metals, has been associated with the etiology and prognosis of many illnesses. However, the specific causal agents and underlying mechanisms for different health outcomes remain unclear. The aims of this study were to assess the relations between urinary biomarkers of exposure to PAHs (1-hydroxypyrene-glucuronide, 1-OHPG) and heavy metals (cadmium, Cd; nickel, Ni; arsenic, As; lead, Pb; and copper, Cu) and the effect of their interaction on DNA damage (8-oxo-7,8-dihydro-guanine, 8-oxodG).

Methods: We recruited 91 traffic conductors and 53 indoor office workers between May 2009 and June 2011 in Taipei, Taiwan. Postshift urine samples from 2 consecutive days were analyzed for 1-OHPG, Cd, Ni, As, Pb, Cu, and 8-oxodG. To estimate the effects from PAHs and metals on DNA damage, we constructed a linear mixed model adjusted for confounding variables.

Results: We found that urinary 1-OHPG and Cd levels were independent predictors of urinary 8-oxodG levels (β = 0.112; P = 0.015 for 1-OHPG; β = 0.138; P = 0.031 for urinary Cd). The joint effect of urinary 1-OHPG and Cd levels was associated with urinary 8-oxodG levels (P = 0.001).

Conclusions: Co-exposure to environmental PAHs and Cd could cause oxidative DNA damage.

Impact: These findings suggest that the additive interaction between exposure to environmental PAHs and Cd could enhance the burden of oxidative stress. Cancer Epidemiol Biomarkers Prev; 22(1); 102–8. ©2012 AACR.
An Analysis of the Association Between Cancer-Related Information Seeking and Adherence to Breast Cancer Surveillance Procedures
Authors: Tan Andy S.L. , Moldovan-Johnson Mihaela , Gray Stacy W. , Hornik Robert C. , Armstrong Katrina
Published: November 2012

Background: Breast cancer surveillance is important for women with a known history of breast cancer. However, relatively little is known about the prevalence and determinants of adherence to surveillance procedures, including associations with seeking of cancer-related information from medical and nonmedical sources.

Methods: We conducted a longitudinal cohort study of breast cancer patients diagnosed in Pennsylvania in 2005. Our main analyses included 352 women who were eligible for surveillance and participated in both baseline (∼1 year after cancer diagnosis) and follow-up surveys. Outcomes were self-reported doctor visits and physical examination, mammography, and breast self-examination (BSE) at 1-year follow-up.

Results: Most women underwent two or more physical examinations according to recommended guidelines (85%). For mammography, 56% of women were adherent (one mammogram in a year) while 39% reported possible overuse (two or more mammograms). Approximately 60% of respondents reported regular BSE (≥5 times in a year). Controlling for potential confounders, higher levels of cancer-related information seeking from nonmedical sources at baseline was associated with regular BSE (OR, 1.52; 95% CI, 1.01–2.29; P, 0.046). There was no significant association between information-seeking behaviors from medical or nonmedical sources and surveillance with physical examination or mammography.

Conclusions: Seeking cancer-related information from nonmedical sources is associated with regular BSE, a surveillance behavior that is not consistently recommended by professional organizations.

Impact: Findings from this study will inform clinicians on the contribution of active information seeking toward breast cancer survivors' adherence to different surveillance behaviors. Cancer Epidemiol Biomarkers Prev; 22(1); 167–74. ©2012 AACR.
The Epidemiology of Herpes Zoster in Patients with Newly Diagnosed Cancer
Authors: Habel Laurel A. , Ray Gary Thomas , Silverberg Michael J. , Horberg Michael A. , Yawn Barbara P. , Castillo Adrienne L. , Quesenberry Charles P. , Li Yan , Sadier Patricia , Tran Trung N.
Published: November 2012

Background: Given the limited literature, we conducted a study to examine the epidemiology of herpes zoster (HZ) among newly diagnosed cancer patients.

Methods: We identified adult health plan members of Kaiser Permanente Northern California diagnosed with invasive cancer from 2001 to 2005. Electronic health records with inpatient and outpatient diagnoses, laboratory tests, and antiviral medications were used to identify HZ diagnoses from 2001 to 2006. HZ diagnoses and associated complications were confirmed by medical chart review. Treatment with chemotherapy and corticosteroids was used to classify patients by immunosuppression level.

Results: Among 14,670 cancer patients, 424 were diagnosed with HZ during follow-up (median 22 months). The incidence of HZ was 31/1,000 person-year (PY) in patients with hematologic malignancies and 12/1,000 PY in patients with solid tumors. The corresponding 2-year cumulative incidence of HZ was approximately 6% and 2%, respectively. Compared with incidence rates of HZ reported in a general US population, the age- and sex-standardized rates of HZ were 4.8 times higher [95% confidence interval (CI), 4.0–5.6] in patients with hematologic malignancies and 1.9 times higher (95% CI, 1.7–2.1) in those with solid tumors. HZ risk increased with increasing level of immunosuppression. Among HZ cases, 19% with hematologic malignancies and 14% with solid tumors had HZ-associated pain for at least 30 days. The corresponding numbers for nonpain-related complications were 30% and 18%, respectively.

Conclusions: Cancer patients are at substantially increased risk of HZ and among those with HZ, complications are relatively common.

Impact: Better HZ prevention and treatment options for cancer patients are needed. Cancer Epidemiol Biomarkers Prev; 22(1); 82–90. ©2012 AACR.
Meat and Heme Iron Intake and Risk of Squamous Cell Carcinoma of the Upper Aero-Digestive Tract in the European Prospective Investigation into Cancer and Nutrition (EPIC)
Authors: Steffen Annika , Bergmann Manuela M. , Sánchez María-José , Chirlaque Maria-Dolores , Jakszyn Paula , Amiano Pilar , Quirós J. Ramón , Barricarte Gurrea Aurelio , Ferrari Pietro , Romieu Isabelle , Fedirko Veronika , Bueno-de-Mesquita H. B(as). , Siersema Peter D. , Peeters Petra H.M. , Khaw Kay-Tee , Wareham Nick , Allen Naomi E. , Crowe Francesca L. , Skeie Guri , Hallmanns Göran , Johansson Ingegerd , Borgquist Signe , Ericson Ulrika , Egeberg Rikke , Tjønneland Anne , Overvad Kim , Grote Verena , Li Kuanrong , Trichopoulou Antonia , Oikonomidou Despoina , Pantzalis Menelaos , Tumino Rosario , Panico Salvatore , Palli Domenico , Krogh Vittorio , Naccarati Alessio , Mouw Traci , Vergnaud Anne-Claire , Norat Teresa , Boeing Heiner
Published: November 2012

Background: Evidence from prospective studies on intake of meat and fish and risk of squamous cell carcinoma (SCC) of the upper aero-digestive tract (UADT) is scarce. We prospectively investigated the association of meat and fish intake with risk of SCC of the UADT and the possible mechanism via heme iron in the large multicenter European Prospective Investigation into Cancer and Nutrition (EPIC) study.

Methods: Multivariable proportional hazards models were used to estimate relative risks (RR) of SCC of the UADT in relation to intake of total meat, as well as subtypes of meat, fish, and heme iron among 348,738 individuals from 7 European countries.

Results: During an average follow-up of 11.8 years, a total of 682 incident cases of UADT SCC were accrued. Intake of processed meat was positively associated with risk of SCC of the UADT in the total cohort [highest vs. lowest quintile: RR = 1.41; 95% confidence interval (CI) = 1.03–1.94], however, in stratified analyses, this association was confined to the group of current smokers (highest vs. lowest quintile: RR = 1.89; 95% CI = 1.22–2.93). Red meat, poultry, fish, and heme iron were not consistently related to UADT SCC.

Conclusion: Higher intake of processed meat was positively associated with SCC of the UADT among smokers. Although this finding was stable in various sensitivity analyses, we cannot rule out residual confounding by smoking. Confirmation in future studies and identification of biologic mechanisms is warranted.

Impact: Smokers may further increase their risk for SCC of the UADT if they additionally consume large amounts of processed meat. Cancer Epidemiol Biomarkers Prev; 21(12); 2138–48. ©2012 AACR.
Application of the Rosner-Colditz Risk Prediction Model to Estimate Sexual Orientation Group Disparities in Breast Cancer Risk in a U.S. Cohort of Premenopausal Women
Authors: Austin S. Bryn , Pazaris Mathew J. , Rosner Bernard , Bowen Deborah , Rich-Edwards Janet , Spiegelman Donna
Published: November 2012

Background: Lesbian and bisexual women may be at greater risk of breast cancer than heterosexual women during the premenopausal period due to disparities in risk factors.

Methods: With 16 years of prospective data from a large cohort of U.S. women ages 25–58 years, we conducted a breast cancer risk assessment for 87,392 premenopausal women by applying the Rosner–Colditz biomathematical risk prediction model to estimate breast cancer risk based on known risk factors. On the basis of each woman's comprehensive risk factor profile, we calculated the predicted 1-year incidence rate (IR) per 100,000 person-years and estimated incidence rate ratios (IRR) and 95% confidence intervals (CI) for lesbian and bisexual women compared with heterosexual women.

Results: A total of 87,392 premenopausal women provided 1,091,871 person-years of data included in analyses. Mean predicted 1-year breast cancer IRs per 100,000 person-years for each sexual orientation group were heterosexual, 122.55; lesbian, 131.61; and bisexual, 131.72. IRs were significantly elevated in both lesbian (IRR, 1.06; 95% CI, 1.06–1.06) and bisexual (IRR, 1.10; 95% CI, 1.10–1.10) women compared with heterosexual women.

Conclusions: Our findings suggest that both lesbian and bisexual women have slightly elevated predicted breast cancer incidence compared with heterosexual women throughout the premenopausal period.

Impact: Health professionals must ensure that breast cancer prevention efforts are reaching these women. As more health systems around the country collect data on patient sexual orientation, the National Cancer Institute's SEER cancer registry should add this information to its data system to monitor progress in reducing sexual orientation–related disparities in cancer incidence and mortality. Cancer Epidemiol Biomarkers Prev; 21(12); 2201–8. ©2012 AACR.
Human Papillomavirus DNA Methylation as a Potential Biomarker for Cervical Cancer
Authors: Clarke Megan A. , Wentzensen Nicolas , Mirabello Lisa , Ghosh Arpita , Wacholder Sholom , Harari Ariana , Lorincz Attila , Schiffman Mark , Burk Robert D.
Published: November 2012

Sexually transmitted carcinogenic human papillomavirus (HPV) infections are extraordinarily prevalent worldwide. However, most incident HPV infections clear within a few years, whereas a small minority persists to invasive cancer. Recent studies indicate that detection of methylated viral DNA may distinguish women with cervical intraepithelial neoplasia grade 2+ (CIN2+) from those with a carcinogenic HPV-type infection that shows no evidence of CIN2+. Several studies have reported a positive association between methylation of CpG sites in the L1 gene and CIN2+, although there are inconclusive results about methylation of CpG sites in the upstream regulatory region (URR). In this review, we summarize the current state of knowledge on HPV DNA methylation in cervical carcinogenesis, and discuss the merits of different methods used to measure HPV DNA methylation. To follow the promising leads, we suggest future studies to validate the use of methylated carcinogenic HPV DNA as a predictive and/or diagnostic biomarker for risk of cervical cancer among HPV-positive women. Cancer Epidemiol Biomarkers Prev; 21(12); 2125–37. ©2012 AACR.
Are Incidence Rates of Adult Leukemia in the United States Significantly Associated with Birth Cohort?
Authors: Rosenberg Philip S. , Wilson Katherine L. , Anderson William F.
Published: November 2012

Background: Leukemia is a common cancer among U.S. adults but there are few established risk factors. If leukemia risks are substantially influenced by exposures that vary in prevalence across generations, then population incidence rates should vary significantly by birth cohort. However, prior studies have not examined leukemia birth cohort effects using contemporary data and methods.

Methods: We used incidence data from the National Cancer Institute's Surveillance, Epidemiology and End Results Program from 1992 through 2009 for adults 25–84 years old and age period cohort models to estimate incidence rate ratios according to birth cohort for acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), chronic myeloid leukemia (CML), and chronic lymphoid leukemia (CLL).

Results: Leukemia incidence varied significantly between birth cohorts for each major leukemia type in men and women except female AMLs; changes on the order of 1% per birth year or 20% per generation were observed. The most significant birth cohort signatures were observed for CLLs and AMLs in men, which were decreasing and increasing, respectively, in cohorts born since 1946.

Conclusions: Our results support the hypothesis that adult leukemia risks are significantly modulated by environmental and lifestyle exposures.

Impact: A number of well-established (smoking, certain chemicals, radiation) and newly recognized (obesity) leukemia risk factors are modifiable; ultimately, efforts to promote healthy lifestyles might also help reduce incidence rates of adult leukemia. Cancer Epidemiol Biomarkers Prev; 21(12); 2159–66. ©2012 AACR.
Calcium Intake and Lung Cancer Risk Among Female Nonsmokers: A Report from the Shanghai Women's Health Study
Authors: Takata Yumie , Shu Xiao-Ou , Yang Gong , Li Honglan , Dai Qi , Gao Jing , Cai Qiuyin , Gao Yu-Tang , Zheng Wei
Published: November 2012

Background: Calcium has been implicated in carcinogenesis and linked to the risk of several cancers in epidemiologic studies; however, few studies have investigated the association of calcium intake with lung cancer risk, particularly among nonsmokers.

Methods: We evaluated the association of intakes of calcium and related minerals, assessed through a food frequency questionnaire, with lung cancer risk among 71,267 female nonsmokers who were cancer free at baseline in the Shanghai Women's Health Study, a population-based, prospective cohort study. Multivariate Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI).

Results: During follow-up through December 2009 (median follow-up time: 11.2 years), 428 incident lung cancer cases accrued. The median intakes of dietary calcium, magnesium, and phosphorus were 441, 266, and 935 mg/d, respectively. Intakes of calcium, phosphorus, and the calcium-to-magnesium (Ca:Mg) ratio were inversely associated with lung cancer risk. The corresponding HRs (95% CIs) for the highest compared with the lowest quartile were 0.66 (0.48, 0.91) for calcium, 0.55 (0.36, 0.85) for phosphorus, and 0.62 (0.47, 0.82) for the Ca:Mg ratio. No association was observed for dietary magnesium intake or the use of calcium- or vitamin D-containing supplements.

Conclusions and Impact: Our study provides some of the first evidence suggesting a possible role for increasing dietary calcium intake in lung cancer prevention among female nonsmokers, especially in populations with relatively low calcium intake. Cancer Epidemiol Biomarkers Prev; 22(1); 50–7. ©2012 AACR.
Catenin Family Genes Are Not Commonly Mutated in Hereditary Diffuse Gastric Cancer
Authors: Schuetz Johanna M. , Leach Stephen , Kaurah Pardeep , Jeyes Jennifer , Butterfield Yaron , Huntsman David , Brooks-Wilson Angela R.
Published: November 2012

Background: Approximately one third of the hereditary diffuse gastric cancer (HDGC) families carry germline mutations in the E-cadherin gene (CDH1). Risk prediction in members of families with this rare but deadly cancer could be improved by the identification of additional HDGC genes in non-CDH1 families.

Methods: Affected individuals from 22 CDH1 mutation-negative families were screened for germline mutations in four catenin genes: CTNNA1, CTNNB1, JUP, and CTNND1. Catenins interact closely with E-cadherin molecules in cells, and are therefore logical candidate genes for mutation screening in HDGC families.

Results: No nonsynonymous variants were seen in CTNNA1, CTNNB1, or CTNND1; only JUP contained nonsynonymous variants, of which only two rare variants were predicted to be deleterious.

Conclusion: Catenin genes are not commonly mutated in non-CDH1 HDGC families.

Impact: Germline mutations in CTNNA1, CTNNB1, JUP, or CTNND1 are unlikely to play a major role in HDGC. Cancer Epidemiol Biomarkers Prev; 21(12); 2272–4. ©2012 AACR.
Mapping of Three Genetic Determinants of Susceptibility to Estrogen-Induced Mammary Cancer within the Emca8 Locus on Rat Chromosome 5
Authors: Schaffer Beverly S. , Leland-Wavrin Kristin M. , Kurz Scott G. , Colletti John A. , Seiler Nicole L. , Warren Christopher L. , Shull James D.
Published: November 2012

The ACI rat model of 17β-estradiol (E2)-induced mammary cancer has gained wide use in the study of breast cancer etiology, prevention, and genetics. Emca8, a QTL that determines susceptibility to E2-induced mammary cancer, was previously mapped to rat chromosome 5 (RNO5) in an intercross between resistant Brown Norway (BN) and susceptible ACI rats. In this study, a panel of congenic rat strains, each of which carries BN alleles across a defined segment of RNO5 on the ACI genetic background, was generated and used to map more precisely the Emca8 determinants of mammary cancer susceptibility. Three distinct genetic determinants were localized within Emca8, and two of these were mapped to intervals of less than 15 megabases. Emca8.1 harbors Cdkn2a, Cdkn2b, and other genes and is orthologous to the 9p21 breast cancer locus identified in genome-wide and candidate gene association studies. Emca8.2 harbors Cdkn2c and other genes and is orthologous to the 1p32 locus in humans that is frequently deleted in breast cancers. Both Emca8.1 and Emca8.2 harbor copy number variants that are orthologous to copy number variant regions in humans. Gene expression profiles were defined for mammary tissues from E2-treated ACI and ACI.BN-Emca8 rats to define the impact of Emca8 on gene expression and identify differentially expressed genes residing within Emca8.1 and Emca8.2. This study further illustrates the relevance of the ACI rat model of E2-induced mammary cancer for identifying novel genetic determinants of breast cancer susceptibility and defining the mechanisms through which estrogens contribute to breast cancer development. Cancer Prev Res; 6(1); 59–69. ©2012 AACR.
Enhanced binding of tissue factor-microparticles to collagen-IV and fibronectin leads to increased tissue factor activity in vitro
Authors: Mei Mah Pui , Xiao Yu Pei , Maraveyas Anthony , Ettelaie Camille , Collier Mary E. W.
Published: November 2012

The role of tissue factor (TF)-containing microparticles in clot propagation has been established, but the ability of circulating microparticles to initiate coagulation has been disputed. However, TF-bearing microparticles, particularly endothelial-microparticles generated during disease, may interact with extracellular matrices which in turn can localise circulating TF to sites of injury. In order to examine this hypothesis in vitro, microparticles were isolated from human coronary artery endothelial cells transfected to overexpress TF, tumour-necrosis factor (TNF)α-treated cells or non-transfected cells lacking TF. The ability of microparticles to bind collagen-IV, fibronectin and fibrin was examined under static conditions and arterial shear rates (650 s-1), and also in the presence of inhibitory antibodies against β1-, β3-, α3-and αv-integrins or an anti-TF antibody. TF-microparticles showed increases of up to 43% and 24% in adherence to collagen-IV and fibronectin, respectively, compared to control microparticles under shear flow. Furthermore, TF-containing microparticles, but not the transfected parent cells had increased levels of β1-integrin compared to TF-deficient microparticles. Pre-incubation of microparticles with a β1-integrin-blocking antibody counteracted the additional adhesion of TFmicroparticles compared to control microparticles. Finally, adherence of TF microparticles to collagen-IV or fibronectin resulted in increased TF activity by concentrating TF onto the surface. In conclusion, the presence of TF within microparticles enhances the interactions of endothelial cell-derived microparticles with extracellular matrices in an integrin-dependent manner. Accumulation and localisation of these microparticles in turn results in the enhancement of TF activity. This may be an innate mechanism by which TF-bearing microparticles induce coagulation upon vascular injury.
Endothelial microparticle release is stimulated in vitro by purified IgG from patients with the antiphospholipid syndrome
Authors: Clarke Lindsey A. , Brogan Paul A. , Latchman David S. , Isenberg David A. , Ioannou Yiannis , Giles Ian P. , Rahman Anisur , Pericleous Charis
Published: November 2012

IgG antiphospholipid antibodies (aPL) exert direct effects on various cell types, contributing to the pathogenesis of thrombosis and pregnancy morbidity in patients with the antiphospholipid syndrome (APS). Some IgG samples from these patients activate endothelial cells (EC) in vitro as judged by surface expression of adhesion molecules such as E-selectin, which can promote thrombosis. Endothelial micro-particles (EMP), which themselves are potentially prothrombotic, are released by activated EC. Though elevated circulating EMP levels have been reported in patients with APS, it is not known whether these EMP are released due to a direct effect of aPL on the cells. We tested the effect of purified polyclonal IgG from patients with APS (APS-IgG) and healthy controls (HC-IgG) upon cultured human umbilical vein EC (HUVEC). HUVEC exposed to APS-IgG produced significantly more EMP than those exposed to HC-IgG (p=0.0036) and a greater proportion of these EMP carried surface E-selectin (6.2% ± 4.0 for APS-IgG vs. 3.4% ± 2.0 for HC IgG, p=0.0172). This study therefore demonstrates that purified polyclonal APS-IgG can drive EMP release. We propose that EMP generation may be a useful measure of aPL-mediated pathogenic effects upon EC.
Temporality and Emergences in Education
Authors: Go Nicolas
Published: November 2012

Abstract

It is striking to note to what extent the time issue in education is commonly understood in terms of chronology. It is an institutional and linear time that is divided and then fitted back together like a Russian doll in an analytical approach. The conception of time is reversible and possesses the same characteristics as space.

It is a paradox that this institutional rationalization of time by reversible chronological divisions barely conceals the whole concrete and living reality of human time, which is a continuous process of change that philosophers generally call duration. On the contrary, far from the above reduction, its specificity lies in its irreversibility.

This article intends to present both the results of empirical research on cooperative pedagogy and its current theorization. The emergence of complexity in time is visible in the primacy given to processes in the educational relationship. The way the multiple scales of complexity are superposed is reflected in the cooperative organization of work, for a new educational temporality which results in an increase in joyful emergences.
Apollo, Helios, and the Solstices in the Athenian, Delphian, and Delian Calendars
Authors: Bilić Tomislav
Published: November 2012

Abstract

The mythical narrative of Apollo’s northern voyage and the place of his festivals in several Greek calendars, reflected also in local ritual practice, seems to reflect certain elements in his nature best explained through his association with the sun, more precisely, the annual solar movement. The association was noted long ago, but a selective analysis will show that both the narrative and the ritual reflect the model of annual solar motion expressed in terms of a suspended reference, a mythical metaphor, a linear narrative defined both by the very nature of language and the celestial phenomenon it is describing. The analysis of various Greek calendars supports the notion of the solstices as the most important defining moments in the annual solar motion, and their connection with Apollo reflects precisely this fact.
From Harrods to Africa: The Travels of a Lion Called Christian
Authors: Nyman Jopi
Published: November 2012

Abstract

This essay is a postcolonial reading of the recently republished auto/biographyA Lion Called Christian(2009; originally published in 1971), written by two Australians, Anthony Bourke and John Rendall. The book narrates the unlikely story of raising a lion in Chelsea and discusses his eventual repatriation and new life in East Africa. The essay argues that the representation of the animal in the metropolitan and African spaces as portrayed in the book can be read critically in the context of the cultural legacy of British colonialism and the role of exotic animals in particular. The essay shows that the function of the animal in the book is to problematize the naturalized division of space into human and animal spaces. As a result, the book deconstructs colonialist and anthropocentric hierarchies in modern society by revealing moments of hybridity when the values of colonial discourse are open to disruption and critique.
Attitudes on Animal Research Predict Acceptance of Genetic Modification Technologies by University Undergraduates
Authors: Gabriel Kara I. , Rutledge Brook H. , Barkley Cynthia L.
Published: November 2012

Abstract

Public acceptance of genetic modification (GM) technologies may be essential to their continued development, yet few studies have investigated the manner in which demographic and educational factors predict support for GM research. The current study examined attitudes toward animal research and GM in ~400 university undergraduates enrolled in introductory or upper-level psychology courses with material on animal experimentation. Results revealed that men were more accepting of animal and GM research than were women. Enrollment in upper-level psychology classes that addressed specific topics in animal research did not directly predict support for GM research, but such enrollment was associated with increased endorsement of the validity of animal research, which then contributed to acceptance of GM scenarios. The current findings highlight the impact of educational variables on support for animal research, which may then influence attitudes toward GM research.
Residents’ and Tourists’ Knowledge of Sea Lions in the Galápagos
Authors: Lorden Rosanne , Sambrook Richard , Mitchell Robert W.
Published: November 2012

Abstract

This study examined knowledge of sea lions (Zalophus wollebaeki) for both residents and tourists on San Cristóbal Island in the Galápagos, a famous nature tourism destination. Participants (N = 281) obtained through convenience and snowball sampling answered questionnaires about their knowledge of sea lions. Participants with higher education received higher overall scores, but participants’ education and age influenced answers on only a few questions. Residents and tourists obtained comparable overall scores, exhibiting extensive knowledge of sea lion behavior and life history. Whether participants were residents or tourists influenced answers to several questions, but when only participants with 13 years of education or more were examined, few differences in answers remained between residents or tourists. Participants’ broad knowledge of sea lions may be attributed to the items of knowledge tested, participants’ motivations for travel to the Galápagos, and the fact that sea lions are an engaging and ubiquitous animal.
Over-burdened Society, Over-politicised State: Understanding Pakistan’s Struggles with Governance
Authors: Murtaza Niaz
Published: November 2012

Abstract

Beset by serious governance problems, Pakistan is often called a failed state. Using the concepts of state-in-society, burdened societies and over-politicised states, this article argues that the nature of a society’s social and political structures, such as social inequality and ethnic divisions, determines the quality of governance institutions that can emerge within it at any given time. These structures emerge from the country’s pre-independence socio-political inheritances and then evolve under the influence of subsequent external and internal factors. In order to analyse a country’s future governance prospects and socio-economic trajectory, one must study the trajectory of these societal structures. Using this framework, the article concludes that while doomsday predictions about Pakistan’s collapse or take-over by religious extremists are inaccurate, it suffers from serious socio-economic problems, which will only resolve gradually if its societal structures evolve over the years in a positive direction.
Introduction Migrant Workers Between States: In Search of Exit and Integration Strategies in South East Asia
Authors: Kneebone Susan
Published: November 2012

Abstract

This Introduction analyses the rights of migrant workers in Southeast Asia according to the obligations of sending and receiving states as provided in the 2007 ASEAN Declaration on the Protection and the Promotion of Rights of Migrant Workers. The implementation of such rights is discussed at three levels of policy: the national, bilateral and multilateral. Gaps in strategies relating to exit and integration of migrant workers are identified. It is argued that migrant workers are situated between the sending and receiving states, but that it is unclear to which they can turn for protection.
International Labour Migration and Migration Policies in Southeast Asia
Authors: Hugo Graeme
Published: November 2012

Abstract

Labour migration is the dominant form of international migration in the Southeast Asian region. It involves movement both within and outside the region with Southeast Asia having some of the world’s major origin and destination countries for labour migrants. There is a bifurcation in policies toward labour migrants between high-skilled and low-skilled workers. While there is a manifest demand for both groups, the former are welcomed and enjoy an array of freedom and rights, while the latter are reluctantly accepted under tight restrictive conditions. The failure to recognise that labour migration is a continuing structural feature of Southeast Asian economies has been a significant barrier to migration being able to deliver the maximum potential positive outcomes, not only to the migrants, but also to the economies of origin and destination countries. There is a pressing need for a more evidence-driven, rights-based approach to all labour migration and a shift from the dominance of a policing model to a management model of governance. There are a number of promising developments in the region with respect to labour migration policy but it still suffers from a lack of management capacity, poor governance, ‘rent taking’, corruption and mismanagement. There is a pressing need for the development and adoption of best practice models, especially in relation to low-skilled migration.
The “Bitter Waters” of Numbers 5:11-31
Authors: Feinstein Eve Levavi
Published: November 2012

Abstract

The phrase מי המרים in Num 5:18, 19, 23, and 24 has been interpreted variously. This article contends that the common translation “bitter waters” is preferable to proposed alternatives.