bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract B68: Curcumin-induced expression of 15-hydroxyprostaglandin dehydrogenase in normal gastric mucosa RGM-1 cells: Possible involvement of AP-1
Authors: Lee Young Wook , Jang Ji-Hye , Park Jong-Min , Surh Young-Joon , Na Hye-Kyung
Published: June 2012

Overproduction of prostaglandin E2 (PGE2) has been reported to be implicated in carcinogenesis. The intracellular level of PGE2 is regulated not only by its biosynthesis, but also by the degradation process. 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is the key enzyme that catalyzes the first step in the inactivation of PGE2. In the present study, we have found that curcumin, a yellow colouring agent present in the rhizome of Curcuma longa Linn (Zingiberaceae), induced expression of 15-PGDH in normal rat gastric mucosa cells (RGM-1) in a concentration and time dependent manner. The mRNA level of 15-PGDH was also increased by curcumin treatment. By using deletion constructs of 15-PGDH promoter, we found that activator protein-1 (AP-1) is the most essential transcription factor responsible for curcumin-induced upregulation of 15-PGDH expression. Curcumin induced phosphorylation of ERK1/2 and JNK1/2, but did not affect activation of p38 MAP kinase. However, treatment with U0126 and SP600125, pharmacological inhibitors of ERK and JNK, respectively failed to suppress the induction of 15-PGDH expression in curcumin-treated RGM-1 cells. Curcumin enhanced the expression of c-Jun, c-fos and CREB in the nuclear fraction of RGM-1 cells. In contrast, tetrahydrocurcumin which lacks the α,β-unsaturated carbonyl group failed to induce expression 15-PGDH, suggesting that the electrophilic α,β-unsaturated carbonyl group of curcumin plays a critical role in its induction of 15-PGDH expression in RGM-1 cells. These results suggest that curcumin-induced expression of 15-PGDH may be mediated by activation of AP-1 transcription factor.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):B68.
Abstract B85: Role of the TASK2 in regulating breast cancer cell proliferation
Authors: Yin Tao , Shepherd Jonathan , Poage Graham , Yang Zhengduo , Chu Lili , Hartman Zachary , Shen Qiang
Published: June 2012

Selective estrogen receptor (ER) modulators (SERMs) such as tamoxifen and raloxifene, and aromatase inhibitors are able to partially reduce incidence in high-risk women to develop ER-positive breast cancer but not all ER-positive neither ER-negative breast cancers. Thus, effective targets and agents for the prevention of both ER-positive and ER-negative breast cancer are urgently needed. Potassium ion channels are essential in maintaining cellular homeostasis in terms of transmitting signal molecules, regulating cell volume and secreting ions and hormones. A family of potassium channels, TASKs, is differentially expressed in normal breast tissue and breast cancer tissues. In particular, TASK2 mRNA was found upregulated in human breast carcinoma but not in normal mammary gland tissue, and TASK2 is significantly up-regulated in ER-negative vs ER-positive breast cancers across multiple studies among the Oncomine databases. We hypothesized that TASK2 plays an important role in regulating growth of breast cancer cells. We then knocked down the TASK2 gene expression using siRNA in ER-positive and ER-negative breast cancer cells. Transient knockdown of TASK2 suppressed cell proliferation significantly in 7/8 ER-negative and moderately in 3/5 ER-positive breast cancer cell lines. However, proliferation of an immortal breast epithelial cell line, MCF-10A, was not affected. We are now investigating the phenotypic alterations in normal and malignant breast cells after overexpressing or knocking down the TASK2 gene. Current results suggest that TASK2 plays an important role in breast cell growth. Thus, TASK2 is a potential novel target for future breast cancer prevention and treatment.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):B85.
Abstract B91: Self-reported prior lung disease as risk factors for non-small cell lung cancer in Mexican Americans
Authors: McHugh Michelle K. , Schabath Matthew B. , Ho Chung-Han , Liu Mei , D'Amelio Anthony M. , Greisinger Anthony J. , Delclos George L. , Spitz Margaret R. , Etzel Carol J.
Published: June 2012

Background: Although cigarette smoking is the primary risk factor for lung cancer, other risk factors have been shown to be associated with lung cancer including prior history of respiratory diseases. The purpose of this analysis was to assess the association between prior history of respiratory disease (i.e., asthma, chronic obstructive pulmonary disease (COPD), hay fever, and pneumonia) and lung cancer among Mexican Americans using data from a multi-racial/ethnic lung cancer case-control study.

Methods: The data were collected between 1991 and 2010. Cases (n = 217) were patients who presented with newly diagnosed, histopathologically confirmed and previously untreated lung cancer. Healthy control participants (n = 339) were recruited from a large multispecialty physician group practice. Demographics, cigarette use, and history of respiratory disease were collected by personal interview using a validated questionnaire. Multivariable logistic regression models were used to estimate relative risk. All analyses were restricted to self-report Mexican Americans.

Results: Prior history of COPD (OR = 2.33; 95% CI = 1.14–4.79) and pneumonia (OR = 2.88; 95% CI = 1.47–5.63) were associated with a statistically significant increased risk of lung cancer. Conversely, self-reported history of asthma (OR = 0.71, 95% CI = 0.20–2.45) or hay fever (OR = 0.59, 95% CI = 0.29–1.21) were inversely associated with lung cancer risk but the odds ratios were not statistically significant.

Conclusions: These findings illustrate that COPD and pneumonia are associated with an increased for lung cancer among Mexican Americans. Identifying risk factors such as C. pneumonia infections and COPD may induce targeted treatments to help attenuate progression to lung cancer. At present this study is one of largest case-control analyses assessing respiratory disease and lung cancer risk among Mexican-Americans.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):B91.
Abstract B97: Soy and green tea intake protect against cervical cancer among Singapore Chinese
Authors: Butler Lesley M. , Wu Anna H. , Montague Julia A. , Koh Woon-Puay , Wang Renwei , Yuan Jian-Min , Yu Mimi C.
Published: June 2012

Background: Cervical cancer incidence is highest in developing countries in Asia and South America and is associated with relatively poor survival in these high-risk populations. Diet may influence susceptibility to and/or persistence of human papillomavirus infection, a necessary cause of cervical cancer. Soy isoflavones and green tea catechins have immunomodulating properties that may protect against cervical cancer.

Methods: We investigated the relationship between soy, green tea and black tea intake and risk of cervical cancer in the well-established prospective population-based Singapore Chinese Health Study. Soy and tea consumption data were collected at baseline using a validated food frequency questionnaire. Cervical cancer cases (n=257) were identified from 34,028 women followed for an average of 11.7 years. Proportional hazards regression methods were used to assess the associations between soy and tea intake and cervical cancer risk. Hazard ratios (HRs) and 95% confidence intervals (CIs) were adjusted for Papanicolaou (Pap) test history, education level, parity, use of oral contraceptives, and other potential confounders.

Results: A statistically significant inverse association was observed for highest versus lowest soy intake and cervical cancer risk (HR=0.71; 95% CI:0.53, 0.96; p for trend=0.03). Consumption of green tea on a weekly or more frequent basis, compared to no tea intake was inversely associated with cervical cancer risk (HR=0.80; 95% CI:0.56, 1.14; p for trend=0.2). There was no association with black tea. We observed interacting effects for soy and green tea intake on risk of cervical cancer. The inverse association with soy intake was stronger among women who drank green tea (HR=0.42; 95% CI:0.25, 0.69; p for trend=0.001). No association was observed for soy intake among non-tea drinkers (p for interaction=0.01).

Conclusions: We provide the first human evidence for individual, as well as synergistic protective effects of soy and green tea intake on risk of cervical cancer. These findings were independent of self-reported frequency of Pap testing and education level. Our findings support experimental evidence for immunomodulating effects of green tea catechins and soy isoflavones as a possible mechanism underlying the protective effect of these dietary factors on cervical cancer risk.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):B97.
Abstract CN01-02: Glycoproteomic discovery of liver cancer biomarkers: Be careful how you use it!
Authors: Block Timothy M.
Published: June 2012

This presentation will describe the discovery and use of the new serum biomarkers of HCC, called GP73 and its fucosylated glycoforms, identified, in part, by comparative glycoproteomics. We will also provide an explanation as to why fucosylated glycoforms are elevated in people with HCC. There are now more than 25 publications reporting that these markers are elevated in the serum of people with HCC, but there are also several papers suggesting they are no better in distinguishing between people with HCC and liver cirrhosis than are other markers such as AFP. We will also provide a theory, supported with data, as to why these differences in observations have occurred. Briefly, the etiology of the HCC, the specific linkage of the glycoform on the putative cancer biomarker as well as the ability of the cancer cells to re-fucosylate the circulating biomarkers, all play roles in how the markers are sorted and the extent to which they can be used as risk and diagnostic markers of cancer. Failure to take these variables into consideration can result in their underperformance as biomarkers of disease.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):CN01-02.
Abstract CN06-03: Randomized double-blinded phase II trial of esomeprazole versus esomeprazole + two doses of aspirin in Barrett's esophagus patients
Authors: Falk Gary W. , Sontag Steven , Cruz-Correa Marica , Weinberg David , Chak Amitabh , Hur Chin , Fleischer David , Smyrk Thomas , Butar Navtej , Foster Nathan , Romero Yvonne , Corley Douglas , DeVault Kenneth , Marcon Norman , Schnell Thomas
Published: June 2012

Background and Aims: In patients with Barrett's esophagus (BE), reflux-induced injury promotes esophageal adenocarcinoma, presumably through cyclooxygenase 2 (COX-2) related pathways. Proton pump inhibitors (PPIs) and nonsteroidal anti-inflammatory drugs (NSAIDs) may interrupt reflux-associated carcinogenesis by reducing acid exposure and subsequent inflammation. However, clinical trial data regarding the chemopreventive efficacy of a PPI + NSAID combination are limited. The aim of this multi-center, randomized, phase II trial was to assess the effects of a 28-day intervention with esomeprazole 40 mg bid and aspirin 81 mg qd, 325 mg qd, or placebo qd on tissue prostaglandin E2 (PGE2) concentrations in BE patients.

Methods: Using the infrastructure of the Cancer Prevention Network, participants (> 18 years) with histologically confirmed non dysplastic BE were randomly assigned to receive one of three interventions for 28 days: (arm A) esomeprazole 40 mg bid+ aspirin 81 mg placebo qd + aspirin 325 mg placebo qd (n=42); (arm B) esomeprazole 40 mg bid+ aspirin 81 mg qd + aspirin placebo 325 qd (n=63); (arm C) esomeprazole 40 mg bid + aspirin 81 mg qd placebo + aspirin 325 mg qd (n=63). Esophageal biopsies were obtained pre- and post-intervention to assess change in PGE2 concentration as the primary endpoint.

Results: In total, 122 participants were randomized, 121 (99%) completed the trial per protocol, and 115 (94%) were evaluated for the primary endpoint. Baseline characteristics were similar across intervention arms. The absolute change (mean + SD) in tissue PGE2 concentration was −67.6 (229.68) in Arm A, −120.9 (281.28) in Arm B (p = 0.10 vs Arm A) and −174.9 (263.62) in Arm C (p = 0.02 vs Arm A).

Conclusions: In combination with esomeprazole 40 mg twice per day, aspirin 325 mg per day significantly reduced tissue PGE2 concentration in BE patients after a 28-day intervention, as compared to aspirin placebo. Given the relevance of PGE2 pathways in BE-associated carcinogenesis, further evaluation of this chemoprevention strategy in larger, more definitive phase III trials is warranted.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):CN06-03.
Abstract ED02-03: Role of diet, energy balance, nutrition, and the risk for recurrence
Authors: Pierce John P.
Published: June 2012

As the risk for recurrence following breast cancer remains elevated for the majority of women for at least 15–20 years, there is considerable interest in whether the way someone lives their life can improve prognosis. There are now numerous cohort studies that have post diagnoses measures of dietary and physical activity patterns as well as body weight and have reported on associations with recurrence. Two large randomized dietary trials have also reported both primary and secondary analyses. However, there is a degree of inconsistency in the published findings.

This presentation will discuss the evidence for a role of dietary patterns, physical activity and body weight in recurrence. Dietary patterns will include those that are plant based and those with a high animal fat intake, as well as considering the impact of nutritional supplements. It will compare physical activity patterns that include half or multiple times the recommended daily pattern. With respect to obesity, the question is whether the overweight are at increased risk as well as those who are obese, and whether there are any obese women who are not at increased risk. Finally, the presentation will consider whether the real issue is not a particular lifestyle pattern but a cluster of behavioral patterns that are linked to increased risk of recurrence.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):ED02-03.
Abstract ED03-03: Analysis of DNA methylation arrays in population studies: Issues and opportunities
Authors: Houseman E. Andres , Accomando William P. , Kelsey Karl T. , Wiencke John K.
Published: June 2012

Epigenetics is the study of heritable changes in gene function unexplained by changes in DNA sequence, and is one of the modes by which environment is thought to interact with genetics. As such, epigenetic alterations constitute an important type of genome-scale variable mediating between environment and disease, and present unique opportunities for conducting epidemiological research. The most commonly studied type of epigenetic alteration in population studies is cytosine methylation, which is a well recognized mechanism of gene silencing that often becomes dysregulated in cancer, and is also thought to be implicated in other diseases. Arrays are now being used to study DNA methylation at a large number of loci; for example, the older Illumina Infinium platform assesses DNA methylation at 27,000 loci, while the newer Infinium array measures DNA methylation at over 470,000 sites. In this talk, we introduce the biology of DNA methylation and survey recent methods for statistical analysis of DNA methylation array data. Finally, we introduce a novel use of DNA methylation arrays to interrogate the distribution of white blood cells, an advancement in the use of DNA methylation to study immunological response as a function of disease status.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):ED03-03.
Abstract ED05-04: Harnessing the power of social media in cancer control communication
Authors: Chou Wen-Ying Sylvia
Published: June 2012

The presentation will review current social media-based health communication programs applied in a variety of health areas, including cancer addition, obesity and sexual health. Beginning with a broad description of the public's health-related social media use, I will summarize types of interventions and illustrate them with specific exemplary projects. Special attention will be given to issues of measurement and evaluation; in particular I will discuss how social media utilization, reach, and impact are measured with respect to health-related attitudes and behaviors.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):ED05-04.
Abstract PL01-01: Advances in functional cancer genomics
Authors: Hahn William C.
Published: June 2012

Recent advances in genomics now make it possible to consider enumerating all of the genetic lesions in specific cancers. While these approaches will yield critical information regarding the identify, number, and types of alterations found in human tumors, a complementary approach to decipher the molecular basis of malignant transformation depends upon the application of genome scale tools to annotate the function of genes involved in cancer initiation and progression. Over the past several years, we have developed genome scale RNAi libraries and open reading frame expression libraries that permit a systematic evaluation of genes involved in cancer initiation and maintenance. Using these libraries, we have now performed screens in a panel of human cancer cell lines to systematically identify cancer vulnerabilities. By combining these functional approaches with information derived from mapping the structural abnormalities present in cancer genomes, we have identified several new oncogenes that contribute to cancer development. The ability to systematically manipulate gene expression at genome scale now provides opportunities to investigate the function of genes involved in cancer initiation and maintenance, which will provide a framework for therapeutic and prevention strategies.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):PL01-01.
Abstract PL01-03: Quantitative biology and biomarker discovery without immunoassays
Authors: Carr Steven A.
Published: June 2012

Lack of antibody reagents and robust quantitative methods with sufficient sensitivity, specificity, reproducibility and throughput has significantly hampered our ability to understand dynamic, protein-based biological processes. My laboratory is addressing this serious barrier by developing targeted mass spectrometry-based technologies to screen and quantify low abundance proteins in a variety of biological contexts including human tissue and plasma. These assays are highly multiplexed, sensitive and specific and do not suffer from interferences that plague immunoassays. Targeted MS-based approaches are helping to usher in a new era of quantitative biology where proteins of interest and their modifications can be robustly measured in any biological context. We are applying these quantitative approaches in the context of a generalizable proteomics-based discovery-through-verification pipeline to identify early biomarkers of cardiovascular injury, breast cancer and infectious disease. These studies are beginning to demonstrate that modern proteomic technologies when coherently integrated can yield novel, credentialed protein biomarker candidates of sufficient merit to warrant real clinical evaluation.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):PL01-03.
Abstract SS01-01: Using genomic technologies to improve cancer risk assessment
Authors: Offit Kenneth
Published: June 2012

The heritable fraction of human cancers, estimated from genetic and epidemiologic approaches, is 21–42%. Heritable cancers include common adult onset malignancies (e.g. prostate, colon, breast cancers) as well as rarer cancers. During past decades, genetic approaches (e.g. linkage analysis and positional cloning) identified rare genetic mutations associated with markedly elevated cancer risk, with subsequent translation of these findings into effective preventive interventions. Recently genomic approaches (e.g. genome wide association studies [GWAS] exploiting linkage disequilibrium between single nucleotide polymorphisms in the human genome) have identified common variants of lower disease risk, as well as common variants which modify the risk of high-penetrance rare alleles. Ongoing studies are utilizing next-generation massively parallel sequencing (NGS) of whole exomes and genomes to identify the “missing heritability” of human cancer. The status GWAS and NGS approaches to cancer risk assessment will be reviewed. The large sample sizes required for GWAS will be emphasized; a case example of our recent consortium effort to identify genomic modifiers of BRCA2 penetrance will be cited. While the methods of identification of genomic variants are distinct, the principles of biomarker identification and clinical translation to preventive oncology are shared. These similarities include: the use of clinically validated variants that may not be functionally characterized; the segregation of these variants in non-Mendelian as well as Mendelian patterns; the role of gene–environment interactions; the dependence on evidence for clinical utility; the critical translational role of behavioral science; and common ethical considerations. It will be emphasized that during the current period of transition from investigation to practice, consumers must also be protected from harms of premature translation of research findings, while encouraging the innovative and cost-effective application of genomic discoveries that improve personalized oncologic care.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):SS01-01.
An Antagonist for CCR4 Alleviates Murine Allergic Rhinitis by Intranasal Administration
Authors: Qi Hui , Zheng Yi , Xu Enquan , Guo Changyuan , Zhang Yan , Sun Qianying , Xiao Junhai , Ma Dalong , Wang Ying
Published: June 2012

Background: CCR4 is highly expressed on Th2 cells. These cells play an important role in acute inflammatory responses, including those involved in allergic rhinitis. We determined whether disrupting the CCR4 ligand interaction with CCR4 antagonist could alleviate allergic rhinitis in a mouse model. Methods: BALB/c mice were sensitized with ovalbumin and alum by intraperitoneal injection and challenged with intranasally administered ovalbumin. Compound 22, which has been reported as a novel small-molecule antagonist of CCR4, was also administered intranasally. In addition, budesonide, an efficient glucocorticoid, was used as a positive control. The effects of compound 22 were quantified by multiple parameters of allergic responses in both nasal and pulmonary tissues. Results: Compound 22 significantly improved symptoms of allergic rhinitis and suppressed levels of total IgE of serum. It dramatically reduced the levels of IL-4 in bronchoalveolar lavage fluid and also decreased the number of inflammatory cells in the fluid. The infiltration of inflammatory cells, especially eosinophils, was markedly reduced in the nasal and pulmonary tissues. The number of IL-4+ cells was also significantly reduced in these tissues. Moreover, the numbers of Foxp3+ cells and IL-17+ cells were reduced, though not to a statistically significant degree. Conclusions: In our research, CCR4 antagonists such as compound 22 were proven for the first time to alleviate murine allergic rhinitis when administered nasally. CCR4 antagonists may have therapeutic potential for the treatment of allergic rhinitis.
How Can We Better Classify NSAID Hypersensitivity Reactions? – Validation from a Large Database
Authors: Caimmi Silvia , Caimmi Davide , Bousquet Philippe-Jean , Demoly Pascal
Published: June 2012

Background: Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) is one of the most common drug hypersensitivities. Several clinical subtypes have been distinguished depending on symptomatology (respiratory, cutaneous, anaphylaxis), timing (immediate, delayed), underlying chronic disease (asthma, chronic urticaria) or putative mechanism of the reaction (allergic, nonallergic mediated). The aim of the present study was to better classify the many hypersensitivity reactions to NSAIDs. Methods: In the present retrospective study, during an 11-year study period, we collected data from all patients with a proven NSAID hypersensitivity. Reactions were classified according to clinical patterns, chronology, underlying diseases and the results of oral provocation tests into 5 and 7 groups in line with two published classifications, respectively. Results: Forty-nine and 88 out of 307 reactions (in 122 patients) could not be classified on the basis of the two previously published classifications. We created a new classification which could include all patient reactions. Conclusions: Our new classification is more suitable for clinical expression of NSAID hypersensitivity. It allows clinicians to identify patients at a high risk, based on the clinical history and clinical manifestations. Moreover, it is helpful for a better understanding and teaching of these reactions.
Hepatic Extramedullary Hematopoiesis and Macrophages in the Adult Mouse: Histometrical and Immunohistochemical Studies
Authors: Sonoda Yuji , Sasaki Kazunobu
Published: June 2012

Fetal liver hematopoiesis in mice disappears approximately 2 weeks after birth; however, under experimental acute anemia extramedullary hematopoiesis occurs in the livers of adult mice. The hematopoietic foci in the liver during extramedullary hematopoiesis contain erythroblasts and macrophages. In this study, the extent of involvement of macrophages in the development and involutional process of the hematopoietic foci in adult mice livers was clarified by experimentally inducing extramedullary hematopoiesis. Hematopoietic cells appeared in the livers 2 days after phenylhydrazine (PHZ) injections. The number and area of the foci increased rapidly, reaching peak values on the sixth day. F4/80-positive macrophages were observed in the sinusoids as well as the hematopoietic foci, and were tightly surrounded by erythroblasts. Sinusoidal macrophages in normal adult livers were positive for F4/80 but negative for ER-HR3. However, in extramedullary hematopoiesis-induced livers, sinusoidal macrophages became positive for ER-HR3 antibodies. The number of ER-HR3-positive macrophages was 9.2 ± 2.9/mm2 on the second day after PHZ was administered, and increased to 200.3 ± 4.2/mm2 on the sixth day. On the seventh day after the PHZ injections, the number decreased and they were no longer detected at 30 days after PHZ was injected. The present study revealed that erythroblasts accumulate around sinusoidal macrophages to form an erythroblastic island with a central macrophage similar to erythropoiesis in the fetal liver. Furthermore, in line with development and regression of extramedullary hematopoiesis, macrophages express ER-HR3, a hematopoiesis related antigen.
Idiopathic Polyhydramnios and Postnatal Abnormalities
Authors: Abele Harald , Starz Sandra , Hoopmann Markus , Yazdi Britta , Rall Katharina , Kagan Karl Oliver
Published: June 2012

Objective: To investigate the proportion and type of fetal anomalies that are associated with polyhydramnios and to examine whether in cases with idiopathic polyhydramnios during the course of pregnancy and fetal anomalies only diagnosed after birth, antenatal characteristics differ. Methods: This was a retrospective study involving all pregnancies with polyhydramnios defined by a deepest pool of amniotic fluid ≥8 cm and a detailed ultrasound examination, a 75 g glucose tolerance test and a TORCH serology. Results: Between 2004 and 2010, 272 pregnancies fulfilled the inclusion criteria. In 89 (32.7%) and 65 (23.9%) cases, there was a fetal anomaly or diabetes. In 118 (43.4%) pregnancies, polyhydramnios was classified as idiopathic. In 11 (9.3%) of the 118 fetuses, an anomaly was found after birth, mainly gastrointestinal atresia. In these cases, median deepest pool of amniotic fluid was 9.6 cm, and median estimated fetal weight was at the 69th centile, whereas in cases without anomalies diagnosed after birth, median deepest pool was 9.0 cm and median estimated fetal weight at the 90th centile (Mann-Whitney U test: deepest pool p = 0.116, and estimated fetal weight centile p = 0.377). There was also no difference in the maternal and gestational age distribution of these cases (Mann-Whitney U test: maternal age p = 0.293, and gestational age p = 0.499). Conclusion: In about 40% of pregnancies, polyhydramnios remains unexplained during the course of pregnancy. In 10% of these cases, an anomaly will only be found after birth. In this group, antenatal characteristics such as amniotic fluid volume, estimated fetal weight or gestational and maternal age at the time of diagnosis do not help to detect these anomalies before birth.
Brugada Syndrome Masked by Ibutilide Treatment in a Patient with Atrial Flutter
Authors: Pagourelias Efstathios D. , Fragakis Nikolaos , Koskinas Konstantinos C. , Geleris Paraschos
Published: June 2012

We present a case of Brugada syndrome in a young patient whose typical ECG pattern was ‘masked’ after ibutilide was administered for atrial flutter cardioversion. Ibutilide, a class III antiarrhythmic agent used for the treatment of atrial fibrillation and flutter, prolongs the action potential duration plateau phase by augmenting the slow component of the inward Na+ current and by blocking the rapid component of the delayed rectifier potassium current. Insights into the pathophysiology of Brugada syndrome and this first-reported action of ibutilide are supplied, providing a plausible scientific basis for the masking effect of ibutilide. Furthermore, issues concerning the safety of ibutilide administration in patients with Brugada syndrome along with the importance of programmed ventricular stimulation and especially short-long-short sequence protocol in inducing ventricular fibrillation in these patients are also discussed.
Whole-Lung Lavage: A Successful Treatment for Restoring Acinar Ventilation Distribution in Primary Acquired Pulmonary Alveolar Proteinosis
Authors: Vanderhelst E. , Hanon S. , Verbanck S. , Schuermans D. , Wissing K. , Bonella F. , Vincken W.
Published: June 2012

A 51-year-old active smoker with primary acquired pulmonary alveolar proteinosis (PAP) diagnosed by biopsy and anti-GM-CSF antibodies was treated safely with whole-lung lavage (WLL). This resulted in a rapid improvement of symptoms and arterial blood oxygenation, but not of standard lung function parameters. However, we also performed the multiple-breath nitrogen washout (MBW) test to determine the lung clearance index (LCI) as well as indices of acinar ventilation heterogeneity (Sacin) and conductive ventilation heterogeneity (Scond). At baseline, a distinct abnormality was seen for Sacin and LCI, while Scond was at the upper limit of normal for this subject. Sacin, in particular, was in excess of the Sacin abnormality corresponding to a 20-pack-year smoking history. Immediately after WLL, Sacin and Scond both fell to within a normal range while LCI also decreased but remained abnormal. The Sacin decrease was much greater than the Scond decrease, which was to be expected after 1 week of smoking cessation at the hospital (smoking was resumed after release from hospital). A follow-up visit 7 weeks after WLL revealed a spectacular improvement on CT scan and improvements in standard lung function. Another follow-up visit 14 weeks after WLL showed further improvements in standard lung function, and both Sacin and Scond remained well within the normal range, and LCI was above the upper limit of normal. We conclude that in this patient, removal of excess surfactant by WLL resulted in a restored ventilation distribution in most of the distal air spaces.
On- versus Off-Pump Coronary Artery Bypass Grafting: No Difference in Early Postoperative Kidney Function Based on TNF-α or C-Reactive Protein
Authors: Nezami Nariman , Djavadzadegan Hassan , Tabatabaie-Adl Haleh , Hamdi Amir , Ghobadi Kazem , Ghorashi Sona , Hajhosseini Babak
Published: June 2012

Background/Aims: There are controversial data about renal function following off-pump coronary artery bypass grafting (CABG). The present study aimed to evaluate renal function changes 24 h after on- and off-pump CABG, as well as renal function correlated with high-sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor-α (TNF-α). Methods: Ninety patients with coronary artery disease referred to our center for CABG from July 2006 to November 2007 were enrolled in the study. Patients were equally and randomly divided in two groups, on- and off-pump. Serum levels of creatinine (Cr), blood urea nitrogen, creatinine clearance (CrCl), hs-CRP, and TNF-α were determined immediately before and 24 h after surgery. Results: Cr and CrCl changes after surgery were not significantly different between the two groups; however, blood urea nitrogen levels after surgery were significantly higher in the on-pump group (p = 0.035). No statistically significant difference was noted between the two groups in terms of changes in levels of hs-CRP and TNF-α (p = 0.350 and 0.805, respectively). The changes in CrCl levels had no significant correlation with hs-CRP and TNF-α. Conclusions: The early Cr and CrCl levels after surgery are not significantly different in on- and off-pump groups. The early renal function after on- or off-pump CABG is not correlated with the levels of inflammatory markers including hs-CRP and TNF-α.
Assessment of a Direct Acoustic Cochlear Stimulator
Authors: Chatzimichalis Michail , Sim Jae Hoon , Huber Alexander M.
Published: June 2012

This study aimed to assess the functional results of a new, active, acoustic-mechanical hearing implant, the Direct Acoustic Cochlear Stimulation Partial Implant (DACS PI), in a preclinical study. The DACS PI is an electromagnetic device fixed to the mastoid by screws and coupled to a standard stapes prosthesis by an artificial incus (AI). The function of the DACS PI-aided reconstruction was assessed by determining: (1) the maximum equivalent sound pressure level (SPL) of the implant, which was obtained from measurements of the volume displacement at the round window in normal and implanted ears, and (2) the quality at the coupling interface between the AI of the DACS and the stapes prosthesis, which was quantified from measurements of relative motions between the AI and the prosthesis. Both measurements were performed with fresh temporal bones using a scanning laser Doppler interferometry system. The expected maximum equivalent SPL with a typical driving voltage of 0.3 V was about 115–125 dB SPL up to 1.5 kHz in reconstruction with the DACS PI, and decreased with a roll-off slope of about 65 dB/decade, reaching 90 dB SPL at 8 kHz. The large roll-off relative to a normal ear was presumed to be a relatively high inductive impedance of the coil of the DACS PI actuator at higher frequencies. Good coupling quality between the AI and the prosthesis was achieved below the resonance (∼1.5 kHz) of the DACS PI for all tested stapes prostheses. Above the resonance, the SMart Piston, which is composed of a shape-memory alloy, had the best coupling quality.
Computed Tomography Osteoabsorptiometry Is Reliable for the Determination of the Subchondral Bone Mineralization Distribution in the Rabbit Knee
Authors: Anetzberger H. , Mayer A. , Schulz C.U. , Müller-Gerbl M.
Published: June 2012

Rabbits are among the most frequently used animals in osteoarthritis research. It is meanwhile accepted that the subchondral bone plate (SBP) plays a key role in the development of osteoarthritis. The most suitable technique for analyzing subchondral bone mineralization is computed tomography osteoabsorptiometry (CT-OAM). Because CT-OAM has not yet been applied to smaller animals, the purpose of this study is to test the reliability of CT-OAM in the rabbit knee. Another important task in animal experiments is the intra- and interindividual difference of the measurement parameters. Our hypothesis is that there is no difference regarding both the position of the density maxima and the bone mineral density (BMD) of the SBP comparing right and left tibial plateaus of rabbits. For evaluating the reliability, a rabbit knee was examined by computed tomography 6 times at weekly intervals. The subchondral mineralization distribution was measured by means of CT-OAM. Positions of the density maxima and BMD of the SBP were determined in a standardized procedure. Furthermore, both parameters were evaluated in 6 female White New Zealand rabbits. Positions of density maxima and BMD in the SBP in left tibial plateaus were compared with right tibial plateaus. The relative coefficient of variation as a parameter for reproducibility was 1.6% for determining the position of the density maxima and 1.2% for measuring the BMD. The positions of density maxima and relative BMD between right and left tibial plateaus varied only about 2% intraindividually, whereas interindividual variance was about 10%. In conclusion, determination of the position of density maxima as well as BMD of the SBP by means of CT-OAM is reliable and reproducible in the rabbit knee. We recommend using the contralateral limb as control, because intraindividual accordance of the mineralization patterns and of the BMD of the SBP was higher than interindividual accordance.
A Model for the Analysis of Caries Occurrence in Primary Molar Tooth Surfaces
Authors: Stephenson J.
Published: June 2012

Recently methods of caries quantification in the primary dentition have moved away from summary ‘whole mouth’ measures at the individual level to methods based on generalised linear modelling (GLM) approaches or survival analysis approaches. However, GLM approaches based on logistic transformation fail to take into account the time-dependent process of tooth/surface survival to caries. There may also be practical difficulties associated with casting parametric survival-based approaches in a complex multilevel hierarchy and the selection of an optimal survival distribution, while non-parametric survival methods are not generally suitable for the assessment of supplementary information recorded on study participants. In the current investigation, a hybrid semi-parametric approach comprising elements of survival-based and GLM methodologies suitable for modelling of caries occurrence within fixed time periods is assessed, using an illustrative multilevel data set of caries occurrence in primary molars from a cohort study, with clustering of data assumed to occur at surface and tooth levels. Inferences of parameter significance were found to be consistent with previous parametric survival-based analyses of the same data set, with gender, socio-economic status, fluoridation status, tooth location, surface type and fluoridation status-surface type interaction significantly associated with caries occurrence. The appropriateness of the hierarchical structure facilitated by the hybrid approach was also confirmed. Hence the hybrid approach is proposed as a more appropriate alternative to primary caries modelling than non-parametric survival methods or other GLM-based models, and as a practical alternative to more rigorous survival-based methods unlikely to be fully accessible to most researchers.
HIV-1 Gag-Virus-Like Particles Inhibit HIV-1 Replication in Dendritic Cells and T Cells through IFN-α-Dependent Upregulation of APOBEC3G and 3F
Authors: Chang Myint Oo , Suzuki Tomoyuki , Yamamoto Norio , Watanabe Megumi , Takaku Hiroshi
Published: June 2012

Human immunodeficiency virus-1 (HIV-1) infection and the acquired immune deficiency syndrome (AIDS) pandemic remain global threats in the absence of a protective or a therapeutic vaccine. HIV-1 replication is reportedly inhibited by some cellular factors, including APOBEC3G (A3G) and APOBEC3F (A3F), which are well known inhibitors of HIV-1. Recently, HIV-1 Gag-virus-like particles (Gag-VLPs) have been shown to be safe and potent HIV-1 vaccine candidates that can elicit strong cellular and humoral immunity without need of any adjuvant. In this report, we stimulated human monocyte-derived dendritic cells (DCs) with Gag-VLPs and we demonstrated that Gag-VLP-treated DCs (VLP-DCs) produced interferon alpha (IFN-α), along with an increase in mRNA and protein expression of A3G and A3F. Gag-VLPs inhibited HIV-1 replication not only in DCs themselves, but also in cocultured T cells in an IFN-α-dependent manner. In addition, A3G/3F content in HIV virions released from VLP-DCs increased. Both the increase in A3G/3F expression and the inhibition of HIV-1 replication were reversed by anti-IFN-α or anti-IFNAR antibodies. Our findings in this study provide insight into the mechanism of Gag-VLP-induced inhibition of HIV-1 replication in DCs and T cells.
Pathogenesis of Small Airways in Asthma
Authors: Hamid Qutayba
Published: June 2012

Asthma is a lung disease characterized by inflammation and remodeling of the airways. It is now widely accepted that airway inflammation and remodeling occur not only in the central airways but also in the small airways and even in the lung parenchyma. Inflammation of the distal lung can be observed even in mild asthmatics with normal or noncompromised lung function. Moreover, the small airways and the lung parenchyma can produce many Th2 cytokines and chemokines involved in initiation and perpetuation of the inflammatory process. In addition, the distal parts of the bronchial tree have been recognized as a predominant site of airflow obstruction in many asthmatics. In fact, the inflammation at this distal site has been described as more severe when compared to the large airway inflammation, and evidence of remodeling in the lung periphery is emerging. Recognition of asthma as a disease of the entire respiratory tract has an important clinical significance, highlighting the need to also consider the distal lung as a target in any therapeutic strategy for effective treatment of this disease.
Porphyromonas gingivalis Accelerates Neointimal Formation after Arterial Injury
Authors: Kobayashi Naho , Suzuki Jun-ichi , Ogawa Masahito , Aoyama Norio , Hanatani Tomoya , Hirata Yasunobu , Nagai Ryozo , Izumi Yuichi , Isobe Mitsuaki
Published: June 2012

Background: Inflammation plays a key role in neointimal hyperplasia after an arterial injury. Chronic infectious disorders, such as periodontitis, are associated with an increased risk of cardiovascular diseases. However, the effects of a periodontal infection on vascular remodeling have not been examined. We assess the hypothesis that periodontal infection could promote neointimal formation after an arterial injury. Methods: Mice were implanted with subcutaneous chambers (n = 41). Two weeks after implantation, the femoral arteries were injured, and Porphyromonas gingivalis (n = 21) or phosphate-buffered saline (n = 20) was injected into the chamber. The murine femoral arteries were obtained for the histopathological analysis. The expression level of mRNA in the femoral arteries was analyzed using quantitative reverse transcriptase polymerase chain reaction (n = 19–20). Results: The intima/media thickness ratio in the P. gingivalis infected group was found to be significantly increased in comparison to the non-infected group. The expression of matrix metalloproteinase-2 mRNA was significantly increased in the P. gingivalis infected group compared to the non-infected group. Conclusion: These findings demonstrate that P. gingivalis injection can promote neointimal formation after an arterial injury. Periodontitis may be a critical factor in the development of restenosis after arterial intervention.
Multiple Authorship and Article Type in Journals of Urology across the Atlantic: Trends over the Past Six Decades
Authors: Hammad Fayez T. , Shaban Sami , Abu-Zidan Fikri
Published: June 2012

Objective: The aim of this research was to study the trends in authorship and type of article in European and North American journals of urology over the past 6 decades. Materials and Methods: Using a self-developed Visual Basic program, the number of authors per article and the type of article in four European journals (BJU International, Current Opinion in Urology, European Urology and Urologia Internationalis) and four North American journals (Journal of Urology, Urologic Clinics of North America, Urology and World Journal of Urology) were extracted from the PubMed website from January 1946 to October 2010, and the number of authors per article in each year was calculated in all the journals. Results: The average number of authors per article has increased and the percentage of single-author articles has decreased in both European and American journals. An increase in the number of authors per article was observed mainly in original articles and case reports. Since the early 1980s, there has also been a decreasing percentage of published case reports and a general increase in the percentage of letters to the editor and editorials. Conclusions: The multiple-authorship trends observed in both European and North American urology journals were similar and appeared to be mainly due to changes in original articles and case reports.
Parenting Practices as Mediators of Child Physical Activity and Weight Status
Authors: Loprinzi Paul D. , Cardinal Bradley J. , Loprinzi Kristina L. , Lee Hyo
Published: June 2012

Understanding the environmental factors that influence children’s physical activity is an important prerequisite before effective physical activity interventions can be developed and implemented. Parenting is one environmental factor that has been empirically shown to positively influence children’s physical activity. However, in order to promote physical activity in children, a better understanding of how parents influence children’s physical activity behavior is required. Previously, Birch and Davison developed a model depicting parental factors hypothesized to influence child dietary behaviors. We extended this model by identifying parental factors hypothesized to promote physical activity in children. This review focuses on the mediational role that parenting practices and behaviors play in influencing child mediators of physical activity behavior, and, ultimately, weight status. Priorities for future research are discussed.