bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Follow-up Study of Physical Activity and Incidence of Colorectal Polyps in African-American Women
Authors: Rosenberg Lynn , Boggs Deborah , Wise Lauren A. , Palmer Julie R. , Roltsch Mark H. , Makambi Kepher H. , Adams-Campbell Lucile L. 
Published: August 2006

Abstract
Background: Physical activity is associated with a reduced risk of colon cancer, but the effect of activity on colorectal adenomas, which are precursors to colon cancer, is uncertain. The influence of physical activity on colorectal adenomas among African-American women is of particular interest because African-American women have an increased risk of colon cancer relative to other U.S. women.
Methods: We prospectively assessed the relation of physical activity to the incidence of colorectal polyps among African-American women. We followed 45,400 women in the Black Women's Health Study from 1997 to 2003. Data were obtained by biennial mailed questionnaires. During 287,029 person-years of follow-up, 1,390 women reported having been diagnosed with colorectal polyps. A review of medical records of 58 women who reported colorectal polyps indicated that 59% had adenomas and 41% had hyperplastic polyps. We converted hours per week of vigorous exercise and hours per week of walking to metabolic equivalent (MET)-hours. We estimated incidence rate ratios with Cox proportional hazard models, controlling for age, body mass index, smoking, family history of colorectal cancer, and education.
Results: For total MET-hours/wk spent in walking and vigorous exercise, the incidence rate ratio decreased from 0.94 for &lt;5 MET-hours/wk to 0.72 for ≥40 MET-hours/wk (Ptrend = 0.01). The inverse association was apparent among most subgroups examined, including women who may be at higher risk of colorectal adenomas because of being obese.
Conclusions: Increased physical activity is associated with a reduced incidence of colorectal polyps among African-American womend. (Cancer Epidemiol Biomarkers Prev 2006;15(8):1438–42)
A Phase I Study of myo-Inositol for Lung Cancer Chemoprevention
Authors: Lam Stephen , McWilliams Annette , leRiche Jean , MacAulay Calum , Wattenberg Lee , Szabo Eva 
Published: August 2006

Abstract
Introduction: A phase I, open-label, multiple dose, dose-escalation clinical study was conducted to assess the safety, tolerability, maximum tolerated dose, and potential chemopreventive effect of myo-inositol in smokers with bronchial dysplasia.
Materials and Methods: Smokers between 40 and 74 years of age with ≥ 30 pack-years of smoking history and one or more sites of bronchial dysplasia were enrolled. A dose escalation study ranging from 12 to 30 g/d of myo-inositol for a month was first conducted in 16 subjects to determine the maximum tolerated dose. Ten new subjects were then enrolled to take the maximum tolerated dose for 3 months. The potential chemopreventive effect of myo-inositol was estimated by repeat autofluorescence bronchoscopy and biopsy.
Results: The maximum tolerated dose was found to be 18 g/d. Side effects, when present, were mild and mainly gastrointestinal in nature. Using the regression rate of the placebo subjects from a recently completed clinical trial with the same inclusion/exclusion criteria as a comparison, a significant increase in the rate of regression of preexisting dysplastic lesions was observed (91% versus 48%; P = 0.014). A statistically significant reduction in the systolic and diastolic blood pressures by an average of 10 mm Hg was observed after taking 18 g/d of myo-inositol for a month or more.
Conclusion: myo-Inositol in a daily dose of 18 g p.o. for 3 months is safe and well tolerated. The potential chemopreventive effect as well as other health benefits such as reduction in blood pressure should be investigated further. (Cancer Epidemiol Biomarkers Prev 2006;15(8):1526–31)
Deletion Polymorphism of UDP-Glucuronosyltransferase 2B17 and Risk of Prostate Cancer in African American and Caucasian Men
Authors: Park Jong , Chen Lan , Ratnashinge Luke , Sellers Thomas A. , Tanner Jean-Paul , Lee Ji-Hyun , Dossett Nicole , Lang Nicholas , Kadlubar Fred F. , Ambrosone Christine B. , Zachariah Babu , Heysek Randy V. , Patterson Stephen , Pow-Sang Julio 
Published: August 2006

Abstract
Purpose: UDP-glucuronosyltransferases (UGT) are a family of enzymes that glucuronidate many endogenous chemicals, including androgens. This makes them more hydrophilic, alters biological activity, and facilitates their excretion. A deletion polymorphism in the UGT2B17 gene was recently described that was associated with a reduced rate of glucuronidation in vivo. The purpose of this study was to determine if the deletion polymorphism is associated with susceptibility to prostate cancer.
Materials and Methods: UGT2B17 expression was determined by reverse transcription-PCR of pathologically normal prostate tissues (n = 5). In a case-control study with 420 patients with incident primary prostate cancer (127 African Americans and 293 Caucasians) and 487 controls (120 African Americans and 367 Caucasians), the frequency of UGT2B17 deletion polymorphism in genomic DNA was compared between cases and controls with PCR analysis.
Results: UGT2B17 mRNA was detected only in individuals with at least one UGT2B17 allele. The frequency of the null genotype was present in 0.11 and 0.12 of Caucasian and African American controls, respectively. When all subjects were considered, a significant association was found between the UGT2B17 deletion polymorphism and prostate cancer risk [odds ratio (OR), 1.7; 95% confidence interval (95% CI), 1.2-2.6]. There was an increase in prostate cancer risk among individuals with UGT2B17 deletion polymorphism in Caucasians (OR, 1.9; 95% CI, 1.2-3.0) but not in African Americans (OR, 1.3; 95% CI, 0.6-2.7).
Conclusions: These results suggest that the UGT2B17 enzyme may play a role in the metabolism of androgens in prostate tissue and that the UGT2B17 deletion polymorphism is associated with prostate cancer risk. (Cancer Epidemiol Biomarkers Prev 2006;15(8):1473–8)
The Cost of Prostate Cancer Chemoprevention: A Decision Analysis Model
Authors: Svatek Robert S. , Lee J. Jack , Roehrborn Claus G. , Lippman Scott M. , Lotan Yair 
Published: August 2006

AbstractBackground: The Prostate Cancer Prevention Trial found reduced prostate cancer prevalence for men treated with finasteride. The public health cost of wide-scale chemoprevention is unclear. We developed a model to help clarify the cost effectiveness of public use of prostate cancer–preventive agents.Methods: A Markov decision analysis model was designed to determine the lifetime prostate health-related costs, beginning at the age of 50 years, for men treated with finasteride compared with placebo. Model assumptions were based on data from the Prostate Cancer Prevention Trial, a literature review of survival and progression rates for patients treated with radical prostatectomy, and costs associated with prostate cancer disease states.Results: Chemoprevention with finasteride resulted in a gain of 13.7 life years per 1,000 men at a cost of $704,000 per life year saved (LYS). However, if finasteride is assumed to not increase the incidence of high-grade tumors, it renders a gain of 21.4 life years per 1,000 men at a cost of $434,000 per LYS; finasteride must cost $15 monthly to reach $100,000 per LYS. When applied to a population at higher risk (lifetime prevalence of ≥30%) for developing prostate cancer, the cost of finasteride must be reduced from its current cost ($62/mo) to &lt;$15 per month for the cost effectiveness to fall below $50,000 per LYS.Conclusions: Given the natural history of treated prostate cancer, implementation of chemoprevention would require an inexpensive medication with substantial cancer risk reduction to be cost effective. Targeting populations at higher risk for developing prostate cancer, however, allows for considerable flexibility in the medication cost to make prostate cancer chemoprevention a more attainable goal. (Cancer Epidemiol Biomarkers Prev 2006;15(8):1485–9)
Lung Cancer Chemoprevention: A Randomized, Double-Blind Trial in Linxian, China
Authors: Kamangar Farin , Qiao You-Lin , Yu Binbing , Sun Xiu-Di , Abnet Christian C. , Fan Jin-Hu , Mark Steven D. , Zhao Ping , Dawsey Sanford M. , Taylor Philip R. 
Published: August 2006

Abstract
We examined the effect of supplementation with four different combinations of vitamins and minerals in the prevention of lung cancer mortality among 29,584 healthy adults from Linxian, China. In accord with a partial factorial design, the participants were randomly assigned to take either a vitamin/mineral combination or a placebo for 5.25 years. The combinations tested in this trial were as follows: factor A, retinol and zinc; factor B, riboflavin and niacin; factor C, ascorbic acid and molybdenum; factor D, β-carotene, α-tocopherol, and selenium. Lung cancer deaths (n = 147) identified during the trial period (1986-1991) and 10 years after the trial ended (1991-2001) were the study outcome. No significant differences in lung cancer death rates were found for any of the four combinations of supplements tested in this study, using log-rank tests (all P values are &gt;0.20) or Cox proportional hazards models adjusted for age, sex, commune, and other treatments. No significant interactions were seen for age, sex, or smoking status. Supplementation with combinations of vitamins and minerals at nutrient-repletion levels for 5.25 years did not reduce lung cancer mortality in this nutrient-inadequate population in Linxian, China. (Cancer Epidemiol Biomarkers Prev 2006;15(8):1562–4)
Exposure of neonates to Respiratory Syncytial Virus is critical in determining subsequent airway response in adults
Authors: You Dahui , Becnel David , Wang Kai , Ripple Michael , Daly Melissa , Cormier Stephania A 
Published: August 2006

AbstractBackgroundRespiratory syncytial virus (RSV) is the most common cause of acute bronchiolitis in infants and the elderly. Furthermore, epidemiological data suggest that RSV infection during infancy is a potent trigger of subsequent wheeze and asthma development. However, the mechanism by which RSV contributes to asthma is complex and remains largely unknown. A recent study indicates that the age of initial RSV infection is a key factor in determining airway response to RSV rechallenge. We hypothesized that severe RSV infection during neonatal development significantly alters lung structure and the pulmonary immune micro-environment; and thus, neonatal RSV infection is crucial in the development of or predisposition to allergic inflammatory diseases such as asthma.MethodsTo investigate this hypothesis the present study was conducted in a neonatal mouse model of RSV-induced pulmonary inflammation and airway dysfunction. Seven-day-old mice were infected with RSV (2 × 105TCID50/g body weight) and allowed to mature to adulthood. To determine if neonatal RSV infection predisposed adult animals to enhanced pathophysiological responses to allergens, these mice were then sensitized and challenged with ovalbumin. Various endpoints including lung function, histopathology, cytokine production, and cellularity in bronchoalveolar lavage were examined.ResultsRSV infection in neonates alone led to inflammatory airway disease characterized by airway hyperreactivity, peribronchial and perivascular inflammation, and subepithelial fibrosis in adults. If early RSV infection was followed by allergen exposure, this pulmonary phenotype was exacerbated. The initial response to neonatal RSV infection resulted in increased TNF-α levels in bronchoalveolar lavage. Interestingly, increased levels of IL-13 and mucus hyperproduction were observed almost three months after the initial infection with RSV.ConclusionNeonatal RSV exposure results in long term pulmonary inflammation and exacerbates allergic airways disease. The early increase in TNF-α in the bronchoalveolar lavage implicates this inflammatory cytokine in orchestrating these events. Finally, the data presented emphasize IL-13 and TNF-α as potential therapeutic targets for treating RSV induced-asthma.
UniFrac – An online tool for comparing microbial community diversity in a phylogenetic context
Authors: Lozupone Catherine , Hamady Micah , Knight Rob 
Published: August 2006

AbstractBackgroundMoving beyond pairwise significance tests to compare many microbial communities simultaneously is critical for understanding large-scale trends in microbial ecology and community assembly. Techniques that allow microbial communities to be compared in a phylogenetic context are rapidly gaining acceptance, but the widespread application of these techniques has been hindered by the difficulty of performing the analyses.ResultsWe introduce UniFrac, a web application available athttp://bmf.colorado.edu/unifrac, that allows several phylogenetic tests for differences among communities to be easily applied and interpreted. We demonstrate the use of UniFrac to cluster multiple environments, and to test which environments are significantly different. We show that analysis of previously published sequences from the Columbia river, its estuary, and the adjacent coastal ocean using the UniFrac interface provided insights that were not apparent from the initial data analysis, which used other commonly employed techniques to compare the communities.ConclusionUniFrac provides easy access to powerful multivariate techniques for comparing microbial communities in a phylogenetic context. We thus expect that it will provide a completely new picture of many microbial interactions and processes in both environmental and medical contexts.
Distinct differentiation characteristics of individual human embryonic stem cell lines
Authors: Mikkola Milla , Olsson Cia , Palgi Jaan , Ustinov Jarkko , Palomaki Tiina , Horelli-Kuitunen Nina , Knuutila Sakari , Lundin Karolina , Otonkoski Timo , Tuuri Timo 
Published: August 2006

Abstract
Background
Individual differences between human embryonic stem cell (hESC) lines are poorly understood. Here, we describe the derivation of five hESC lines (called FES 21, 22, 29, 30 and 61) from frozen-thawed human embryos and compare their individual differentiation characteristic.

Results
The cell lines were cultured either on human or mouse feeder cells. The cells grew significantly faster and could be passaged enzymatically only on mouse feeders. However, this was found to lead to chromosomal instability after prolonged culture. All hESC lines expressed the established markers of pluripotent cells as well as several primordial germ cell (PGC) marker genes in a uniform manner. However, the cell lines showed distinct features in their spontaneous differentiation patterns. The embryoid body (EB) formation frequency of FES 30 cell line was significantly lower than that of other lines and cells within the EBs differentiated less readily. Likewise, teratomas derived from FES 30 cells were constantly cystic and showed only minor solid tissue formation with a monotonous differentiation pattern as compared with the other lines.

Conclusion
hESC lines may differ substantially in their differentiation properties although they appear similar in the undifferentiated state.
Differences in the evolutionary history of disease genes affected by dominant or recessive mutations
Authors: Furney Simon J , Albà M Mar , López-Bigas Núria 
Published: August 2006

Abstract

Background
Global analyses of human disease genes by computational methods have yielded important advances in the understanding of human diseases. Generally these studies have treated the group of disease genes uniformly, thus ignoring the type of disease-causing mutations (dominant or recessive). In this report we present a comprehensive study of the evolutionary history of autosomal disease genes separated by mode of inheritance.

Results
We examine differences in protein and coding sequence conservation between dominant and recessive human disease genes. Our analysis shows that disease genes affected by dominant mutations are more conserved than those affected by recessive mutations. This could be a consequence of the fact that recessive mutations remain hidden from selection while heterozygous. Furthermore, we employ functional annotation analysis and investigations into disease severity to support this hypothesis.

Conclusion
This study elucidates important differences between dominantly- and recessively-acting disease genes in terms of protein and DNA sequence conservation, paralogy and essentiality. We propose that the division of disease genes by mode of inheritance will enhance both understanding of the disease process and prediction of candidate disease genes in the future.
Regulatory role of pro-Th1 and pro-Th2 cytokines in modulating the activity of Th1 and Th2 cells when B cell and macrophages are used as antigen presenting cells
Authors: Singh Vinod , Agrewala Javed N 
Published: August 2006

AbstractBackgroundPresence of antigen presenting cells, expression of costimulatory molecules, the strength of first signal and cytokine milieu are quite important in influencing the reactivation of differentiated Th1 and Th2 cells.ResultsIn the present study, we have analyzed the concerted action of pro-Th1 and pro-Th2 cytokines in the presence of B cells, peritoneal and splenic macrophages as antigen presenting cells and varied concentration of first (anti-CD3 Ab) and second (B7-1 transfectant) signals on the proliferation and cytokine secretion by Th1 and Th2 cells. Interesting observations were made that IFN-γ significantly augmented the secretion of IL-4 by Th2 cells when either B cells or splenic or peritoneal macrophages were used as APC. Further, IFN-γ significantly inhibited the proliferation of Th1 cells only in the presence of peritoneal macrophages. We have also observed that B cells could significantly respond to cytokines to further enhance the proliferation and cytokine release by Th1 and Th2 cells. But not much effect on addition of exogenous cytokines IL-1, IL-4, IL-5, IL-12 was observed on the proliferation of Th1 and Th2 cells in the presence of macrophages. In contrast, both IFN-γ and IL-2 significantly enhanced the production of IL-4 and IL-5 respectively, by Th2 cells in presence of B cells, splenic and peritoneal macrophages. Another important observation was that the addition of B7-1 transfectants in the cultures, which were stimulated with low dose of anti-CD3 Ab significantly, enhanced the proliferation and cytokine secretion.ConclusionThis study indicates involvement of different type of APCs, cytokine milieu, dose of first and second signals in a concerted manner in the outcome of the immune response. The significance of this study is that the immunization with antigen along with costimulatory molecules may significantly reduce the dose of antigen and can generate better immune response than antigen alone.
Characterization of the mrgRS locus of the opportunistic pathogen Burkholderia pseudomallei: temperature regulates the expression of a two-component signal transduction system
Authors: Mahfouz Magdy E , Grayson T Hilton , Dance David AB , Gilpin Martyn L 
Published: August 2006

Abstract

Background

Burkholderia pseudomallei is a saprophyte in tropical environments and an opportunistic human pathogen. This versatility requires a sensing mechanism that allows the bacterium to respond rapidly to altered environmental conditions. We characterized a two-component signal transduction locus from B. pseudomallei 204, mrgR and mrgS, encoding products with extensive homology with response regulators and histidine protein kinases of Escherichia coli, Bordetella pertussis, and Vibrio cholerae.

Results
The locus was present and expressed in a variety of B. pseudomallei human and environmental isolates but was absent from other Burkholderia species, B. cepacia, B. cocovenenans, B. plantarii, B. thailandensis, B. vandii, and B. vietnamiensis. A 2128 bp sequence, including the full response regulator mrgR, but not the sensor kinase mrgS, was present in the B. mallei genome. Restriction fragment length polymorphism downstream from mrgRS showed two distinct groups were present among B. pseudomallei isolates. Our analysis of the open reading frames in this region of the genome revealed that transposase and bacteriophage activity may help explain this variation. MrgR and MrgS proteins were expressed in B. pseudomallei 204 cultured at different pH, salinity and temperatures and the expression was substantially reduced at 25°C compared with 37°C or 42°C but was mostly unaffected by pH or salinity, although at 25°C and 0.15% NaCl a small increase in MrgR expression was observed at pH 5. MrgR was recognized by antibodies in convalescent sera pooled from melioidosis patients.

Conclusion
The results suggest that mrgRS regulates an adaptive response to temperature that may be essential for pathogenesis, particularly during the initial phases of infection. B. pseudomallei and B. mallei are very closely related species that differ in their capacity to adapt to changing environmental conditions. Modifications in this region of the genome may assist our understanding of the reasons for this difference.
Anticancer drug clustering in lung cancer based on gene expression profiles and sensitivity database
Authors: Gemma Akihiko , Li Cai , Sugiyama Yuka , Matsuda Kuniko , Seike Yoko , Kosaihira Seiji , Minegishi Yuji , Noro Rintaro , Nara Michiya , Seike Masahiro , Yoshimura Akinobu , Shionoya Aki , Kawakami Akiko , Ogawa Naoki , Uesaka Haruka , Kudoh Shoji 
Published: August 2006

Abstract

background
The effect of current therapies in improving the survival of lung cancer patients remains far from satisfactory. It is consequently desirable to find more appropriate therapeutic opportunities based on informed insights. A molecular pharmacological analysis was undertaken to design an improved chemotherapeutic strategy for advanced lung cancer.

Methods
We related the cytotoxic activity of each of commonly used anti-cancer agents (docetaxel, paclitaxel, gemcitabine, vinorelbine, 5-FU, SN38, cisplatin (CDDP), and carboplatin (CBDCA)) to corresponding expression pattern in each of the cell lines using a modified NCI program.

Results
We performed gene expression analysis in lung cancer cell lines using cDNA filter and high-density oligonucleotide arrays. We also examined the sensitivity of these cell lines to these drugs via MTT assay. To obtain our reproducible gene-drug sensitivity correlation data, we separately analyzed two sets of lung cancer cell lines, namely 10 and 19. In our gene-drug correlation analyses, gemcitabine consistently belonged to an isolated cluster in a reproducible fashion. On the other hand, docetaxel, paclitaxel, 5-FU, SN-38, CBDCA and CDDP were gathered together into one large cluster.

Conclusion
These results suggest that chemotherapy regimens including gemcitabine should be evaluated in second-line chemotherapy in cases where the first-line chemotherapy did not include this drug. Gene expression-drug sensitivity correlations, as provided by the NCI program, may yield improved therapeutic options for treatment of specific tumor types.