bluuebunny/crossref_metadata_2025 huggingface dataset:
CD38 is required for priming by TNF-α: a mechanism for extracellular coordination of cell fate
Authors: Iqbal Jameel , Zaidi Mone
Published: December 2006

Cytokines are protein messengers that act to modulate the differentiation or activation of their target cells. Bone marrow macrophages can become activated tissue macrophages, dendritic cells, or osteoclasts depending on to which cytokines they are exposed. However, one cytokine can often induce divergent outcomes, suggesting that other signals are needed to establish the specificity of the result. We hypothesize that these signals may derive from the local environment and serve to prime cells to respond toward a specific outcome. Here, it is shown that the cytokine TNF-α is capable of affecting the fate of macrophages by upregulating the NADase CD38. CD38 upregulation primes macrophages, such that signals induced by inflammatory stimuli are augmented, while those leading to osteoclast formation are inhibited. We show that TNF-α-induced CD38 expression negatively affects the expression of osteoclast markers, while it enhances inflammatory gene expression by decreasing ERK1/2 phosphorylation and increasing NF-κB activation. Furthermore, it is shown that CD38 may reduce osteoclastogenesis and increase inflammatory gene induction by decreasing cellular histone deacetylase activity. These results provide a demonstration of how a cytokine can prime cells to differentiate toward a certain lineage or acquire enhanced activation characteristics. Since CD38 is an ectoenzyme, we suggest that the modulation of extracellular NAD+metabolism likely serves as a unique mechanism to coordinate the fate of cells within a local environment.
Responses of the human airway epithelium transcriptome to in vivo injury
Authors: Heguy Adriana , Harvey Ben-Gary , Leopold Philip L. , Dolgalev Igor , Raman Tina , Crystal Ronald G.
Published: December 2006

To identify genes participating in human airway epithelial repair, we used bronchoscopy and brushing to denude the airway epithelium of healthy individuals, sequentially sampled the same region 7 and 14 days later, and assessed gene expression by Affymetrix microarrays with TaqMan RT-PCR confirmation. Histologically, the injured area was completely covered by a partially redifferentiated epithelial layer after 7 days; by 14 days the airway epithelium was very similar to the uninjured state. At day 7 compared with resting epithelium, there were substantial differences in gene expression pattern, with a distinctive airway epithelial “repair transcriptome” of actively proliferating cells in the process of redifferentiation. The repair transcriptome at 7 days was dominated by cell cycle, signal transduction, metabolism and transport, and transcription genes. Interestingly, the majority of differentially expressed cell cycle genes belonged to the G2 and M phases, suggesting that the proliferating cells were relatively synchronized 1 wk following injury. At 14 days postinjury, the expression profile was similar to that of resting airway epithelium. These observations provide a baseline of the functional gene categories participating in the process of normal human airway epithelial repair that can be used in future studies of injury and repair in airway epithelial diseases.
Cardiac myocyte gene expression profiling during H2O2-induced apoptosis
Authors: Clerk Angela , Kemp Timothy J. , Zoumpoulidou Georgia , Sugden Peter H.
Published: December 2006

High levels of oxidative stress promote cardiac myocyte death, though lower levels are potentially cytoprotective/anabolic. We examined the changes in gene expression in rat neonatal cardiac myocytes exposed to apoptotic (0.2 mM) or nontoxic (0.04 mM) concentrations of H2O2(2, 4, or 24 h) using Affymetrix microarrays. Using U34B arrays, we identified a ubiquitously expressed, novel H2O2-responsive gene [putative peroxide-inducible transcript 1 (Perit1)], which generates two alternatively spliced transcripts. Using 230 2.0 arrays, H2O2(0.04 mM) promoted significant changes in expression of only 32 genes, all of which were seen with 0.2 mM H2O2. We failed to detect any increase in the rate of protein synthesis in cardiac myocytes exposed to <0.1 mM H2O2, further suggesting that global, low concentrations of H2O2are not anabolic in this system. H2O2(0.2 mM) promoted significant ( P < 0.05, >1.75-fold) changes in expression of 649 mRNAs and 187 RNAs corresponding to no established gene. Of the mRNAs, 114 encoded transcriptional regulators including Krüppel-like factors (Klfs). Quantitative PCR independently verified the changes in Klf expression. Thus, H2O2-induced cardiac myocyte apoptosis is associated with dynamic changes in gene expression. The expression of these genes and their protein products potentially influences the progression of the apoptotic response.
Body Mass Index, Abnormal Glucose Metabolism, and Mortality from Hematopoietic Cancer
Authors: Chiu Brian C-H. , Gapstur Susan M. , Greenland Philip , Wang Renwei , Dyer Alan
Published: December 2006

Background: High body mass index (BMI) and diabetes have been linked to risk of non-Hodgkin's lymphoma (NHL), but results are inconsistent and most studies use self-reported information. No study has evaluated the association of NHL with postload plasma glucose (PLG) levels, which are positively associated with BMI. We analyzed data from a cohort study to investigate associations of interviewer-measured BMI and PLG with risk of NHL mortality and to explore associations with leukemia and multiple myeloma.

Methods: Employees of 84 Chicago-area organizations, with an average age of 40 years at baseline, were screened from 1967 to 1973. Height and weight were measured by study nurses. A 50-g oral glucose load was administered to nondiabetic participants. Of the at-risk cohort of 35,420 men and women, 129 died of NHL, 151 died of leukemia, and 66 died of multiple myeloma during an average of 31 years of follow-up. Hazard Ratios (HR) and 95% confidence intervals (95% CI) were derived from Cox proportional hazards regression models.

Results: Among men, there were positive dose-response relations of BMI with mortality from NHL (HR, 2.57; 95% CI, 1.24-5.34 for the highest versus lowest quartile; Ptrend = 0.01) and leukemia (HR, 1.98; 1.07-3.69; Ptrend = 0.02). PLG also was positively related to NHL mortality (HR, 2.86; 95% CI, 1.35-6.06 for the highest versus lowest category; Ptrend = 0.004). For women, a higher BMI was positively associated with leukemia mortality (HR, 2.47; 95% CI, 0.96-6.36; Ptrend = 0.02) and the highest level of PLG was associated with risk of mortality from multiple myeloma (HR, 3.06; 95% CI, 1.05-8.93). The risk estimates for BMI and PLG remained unchanged after adjustment for each factor.

Conclusions: High BMI and/or abnormal PLG is associated with higher risk of mortality from NHL and possibly leukemia and from myeloma in women. These findings might have public health significance because BMI and glucose levels are amenable to modification. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2348–54)
Infant Acute Leukemia and Maternal Exposures during Pregnancy
Authors: Pombo-de-Oliveira Maria S. , Koifman Sergio ,   Brazilian Collaborative Study Group of Infant Acute Leukemia
Published: December 2006

Infant acute leukemia (IAL) has a unique profile characterized by the high incidence of translocations involving the MLL gene located at the 11q23 region. To test the potential role of intrauterine and perinatal factors linked to the risk of IAL development, a hospital-based case-control study was conducted in different cities of Brazil. A total of 202 children (ages 0-21 months) with newly diagnosed IAL was enrolled (1999-2005), and 440 age-matched controls were selected from the same hospitals wherein IAL cases were treated. A statistically significant association between maternal use of hormones during pregnancy and IAL was observed [odds ratio (OR), 8.76; 95% confidence interval (95% CI), 2.85-26.93] in a multivariable analysis. The association of certain exposures during pregnancy (hormones, dipyrone, metronidazole, and misoprostol) and MLL gene rearrangements was tested using a case-case approach. Despite the lack of statistical significance, the magnitude of the OR for maternal exposure to dipyrone (OR, 1.45; 95% CI, 0.75-2.86), metronidazole (OR, 1.72; 95% CI, 0.64-4.58), quinolones (OR, 2.25; 95% CI, 0.70-25.70), and hormones (OR, 1.88; 95% CI, 0.50-7.01) may suggest the occurrence of interactions between such maternal exposures during pregnancy and MLL rearrangements, yielding into IAL development. The strong and statistically significant association between IAL and estrogen exposure during pregnancy observed in this study deserves further investigation to investigate its role in intrauterine leukemogenesis. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2336–41)
Polymorphisms in Metabolic Genes Related to Tobacco Smoke and the Risk of Gastric Cancer in the European Prospective Investigation into Cancer and Nutrition
Authors: Agudo Antonio , Sala Núria , Pera Guillem , Capellá Gabriel , Berenguer Antonio , García Nadia , Palli Domenico , Boeing Heiner , Del Giudice Giuseppe , Saieva Calogero , Carneiro Fatima , Berrino Franco , Sacerdote Carlotta , Tumino Rosario , Panico Salvatore , Berglund Göran , Simán Henrik , Stenling Roger , Hallmans Göran , Martínez Carmen , Bilbao Roberto , Barricarte Aurelio , Navarro Carmen , Quirós José R. , Allen Naomi , Key Tim , Bingham Sheila , Khaw Kay-Tee , Linseisen Jakob , Nagel Gabriele , Overvad Kim , Tjonneland Anne , Olsen Anja , Bueno-de-Mesquita H. Bas , Boshuizen Hendriek C. , Peeters Petra H. , Numans Mattijs E. , Clavel-Chapelon Françoise , Boutron-Ruault Marie-Christine , Trichopoulou Antonia , Lund Eiliv , Offerhaus Johan , Jenab Mazda , Ferrari Pietro , Norat Teresa , Riboli Elio , González Carlos A.
Published: December 2006

Metabolizing enzymes, which often display genetic polymorphisms, are involved in the activation of compounds present in tobacco smoke that may be relevant to gastric carcinogenesis. We report the results of a study looking at the association between risk of gastric adenocarcinoma and polymorphisms in genes CYP1A1, CYP1A2, EPHX1, and GSTT1. A nested case-control study was carried out within the European Prospective Investigation into Cancer and Nutrition, developed in 10 European countries. The study includes 243 newly diagnosed cases of histologically confirmed gastric adenocarcinoma and 946 controls matched by center, age, sex, and date of blood collection. Genotypes were determined in nuclear DNA from WBCs. We found an increased risk of gastric cancer for homozygotes for C (histidine) variant in Y113H of EPHX1 (odds ratio, 1.91; 95% confidence interval, 1.19-3.07) compared with subjects with TC/TT. There was also a significant increased risk for smokers carrying at least one variant allele A in Ex7+129C>A (m4) of CYP1A1 and never smokers with null GSTT1 and allele A in the locus −3859G>A of CYP1A2. Most of these genes are involved in the activation and detoxification of polycyclic aromatic hydrocarbons, suggesting a potential role of these compounds in gastric carcinogenesis. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2427–34)
Risk of Multiple Myeloma following Medication Use and Medical Conditions: A Case-Control Study in Connecticut Women
Authors: Landgren Ola , Zhang Yawei , Zahm Sheila Hoar , Inskip Peter , Zheng Tongzhang , Baris Dalsu
Published: December 2006

Background: Certain commonly used drugs and medical conditions characterized by chronic immune dysfunction and/or antigen stimulation have been suggested to affect important pathways in multiple myeloma tumor cell growth and survival. We conducted a population-based case-control study to investigate the role of medical history in the etiology of multiple myeloma among Connecticut women.

Methods: A total of 179 incident multiple myeloma cases (21-84 years, diagnosed 1996-2002) and 691 population-based controls was included in this study. Information on medical conditions, medications, and medical radiation was obtained by in-person interviews. We calculated odds ratios (OR) as measures of relative risks using logistic regression models.

Results: A reduced multiple myeloma risk was found among women who had used antilipid statin therapy [OR, 0.4; 95% confidence interval (95% CI), 0.2-0.8] or estrogen replacement therapy (OR, 0.6; 95% CI, 0.4-0.99) or who had a medical history of allergy (OR, 0.4; 95% CI, 0.3-0.7), scarlet fever (OR, 0.5; 95% CI, 0.2-0.9), or bursitis (OR, 0.4; 95% CI, 0.2-0.7). An increased risk of multiple myeloma was found among women who used prednisone (OR, 5.1; 95% CI, 1.8-14.4), insulin (OR, 3.1; 95% CI, 1.1-9.0), or gout medication (OR, 6.7; 95% CI, 1.2-38.0).

Conclusions: If our results are confirmed, mechanistic studies examining how prior use of insulin, prednisone, and, perhaps, gout medication might promote increased occurrence of multiple myeloma and how antilipid statins, estrogen replacement therapy, and certain medical conditions might protect against multiple myeloma may provide insights to the as yet unknown etiology of multiple myeloma. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2342–7)
Accuracy of Multiplexed Illumina Platform-Based Single-Nucleotide Polymorphism Genotyping Compared between Genomic and Whole Genome Amplified DNA Collected from Multiple Sources
Authors: Paynter Randi A. , Skibola Danica R. , Skibola Christine F. , Buffler Patricia A. , Wiemels Joseph L. , Smith Martyn T.
Published: December 2006

Association studies designed to identify the genetic determinants underlying complex disease increasingly require sustainable high-quality DNA resources for large-scale single-nucleotide polymorphism (SNP) genotyping. Recent studies have shown that genomic DNA (gDNA) suitable for SNP genotyping can be obtained from buccal cells and from dried blood spots on Guthrie cards. Further, successful SNP genotyping has been done using the reaction product of multiple displacement amplification of gDNA. We evaluated genotype consistency on the Illumina genotyping platform for 717 to 1,744 SNP loci between replicate samples of gDNA and whole genome amplified DNA (wgaDNA) from a variety of sources. Nine healthy adults provided peripheral blood via venipuncture and buccal cells by mouth rinse. DNA was also obtained from urothelial cells in urine samples from five of the nine subjects. gDNA was extracted from all samples, wgaDNA was generated from each gDNA, and all samples were genotyped. To assess SNP genotyping accuracy of DNA obtained from dried blood spots, gDNA was extracted, amplified, and genotyped from peripheral blood samples and paired Guthrie card samples were obtained from eight childhood leukemia patients. Call rates and replicate concordances for all sample types, regardless of amplification, were >97%, with most sample types having call rates and replicate concordances >99%. Using the gDNA from blood samples as the reference for concordances calculated for all other sample types, we observed concordances >98% regardless of sample type or amplification. We conclude that highly multiplexed Illumina genotyping may be done on gDNA and wgaDNA obtained from whole blood, buccal samples, dried blood spots on Guthrie cards, and possibly even urine samples, with minimal misclassification. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2533–6)
Comprehensive Analysis of 22XPCPolymorphisms and Bladder Cancer Risk
Authors: Sak Sei Chung , Barrett Jennifer H. , Paul Alan B. , Bishop D. Timothy , Kiltie Anne E.
Published: December 2006

Two major risk factors for bladder cancer are smoking and occupational exposure to chemicals. The XPC protein is crucial in the recognition and initiation of the nucleotide excision repair pathway which repairs the DNA adducts formed by carcinogens found in cigarette smoke and chemicals. Polymorphisms in the XPC gene have been shown to influence an individual's DNA repair capacity, and hence, increase that individual's susceptibility to cancer. We undertook a case-control study of 547 bladder cancer cases and 579 cancer-free controls to investigate the association between 22 XPC polymorphisms and bladder cancer susceptibility, and investigated gene-environment interactions. We showed that the nonsynonymous polymorphism Ala499Val was in strong linkage disequilibrium with two polymorphisms in the 3′-untranslated region (Ex15-184 and Ex15-177) with Lewontin's D′ ≥ 0.99 and r2 ≥ 0.82. Individuals homozygous for the minor allele of Ala499Val, Ex15-184, or Ex15-177 had an increased risk of bladder cancer compared with those homozygous for the common allele [adjusted odds ratio (95% confidence interval), 1.65 (1.05-2.59), 1.82 (1.12-2.97), and 1.82 (1.12-2.96), respectively]. The associations were somewhat stronger for smokers and those occupationally exposed to chemicals, although tests for gene-environment interactions were not significant. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2537–41)
Hypoxia-Inducible Factor 1 as a Possible Target for Cancer Chemoprevention
Authors: López-Lázaro Miguel
Published: December 2006

Despite the intense cancer research carried out in the last 30 years, cancer therapy has not managed to decrease cancer mortality. We need new strategies to control a disease that kills over six million people worldwide every year. It is accepted that cancer chemoprevention (the use of chemicals to prevent, stop, or reverse the process of carcinogenesis) is an essential approach to controlling cancer; yet, the clinical usefulness of this strategy is very limited. Successful implementation of cancer chemoprevention depends on a mechanistic understanding of the carcinogenesis process. Our knowledge about this process is still limited and may therefore be preventing cancer chemoprevention from becoming a widely used anticancer tool. This report discusses recent evidence that suggests that the activation of the hypoxia-inducible factor 1 (HIF-1) is a key event in carcinogenesis and may therefore represent a key target for cancer chemoprevention. Based on an understanding of the mechanisms responsible for HIF-1 activation, possible general strategies for targeting HIF-1 are proposed. Successful implementation of these strategies might turn the great promise of cancer chemoprevention into a fundamental tool for reducing the burden of this disease. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2332–5)
Vitamin D Receptor Genotypes/Haplotypes and Prostate Cancer Risk
Authors: Cicek Mine S. , Liu Xin , Schumacher Fredrick R. , Casey Graham , Witte John S.
Published: December 2006

The vitamin D receptor (VDR) gene has been associated with prostate cancer, although previous results are somewhat equivocal. To further study this, we did a family-based case-control study (N = 918) of the association between prostate cancer and six common VDR variants: Cdx2, FokI, BsmI, ApaI, TaqI, and the poly-A microsatellite. Looking at each variant alone, only FokI and ApaI were associated with disease. The FokI FF genotype was inversely associated with prostate cancer among men with less advanced disease (i.e., Gleason score <7 and tumor stage <T2c), where the odds ratio OR was 0.56 [95% confidence interval (95% CI), 0.31-1.01; P = 0.05]. ApaI, carrying one or two copies of the A allele, exhibited a weak inverse association with disease (OR, 0.64; 95% CI, 0.39-1.03; P = 0.06); this association was strengthened in Caucasian men with more advanced disease (OR, 0.44; 95% CI, 0.21-0.93; P = 0.03). We observed inverse associations between disease and the four-locus FBAt haplotype (OR, 0.48; 95% CI, 0.30-0.76; P = 0.002) and the fbaT haplotype (OR, 0.60; 95% CI, 0.38-0.95; P = 0.03; i.e., in comparison with the FbaT haplotype). These were stronger among men with more advanced disease: for FBAt, the OR was 0.31 (95% CI, 0.16-0.61; P = 0.0008); for fbaT, the OR was 0.32 (95% CI, 0.16-0.64; P = 0.001). These observations support a role for VDR variants in prostate cancer risk but suggest that any potential causal variant(s) may reside on the haplotypes reported here. This would help explain the somewhat equivocal results for VDR genotype-level associations with prostate cancer. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2549–52)
Association of Genetic Variants of O6-Methylguanine-DNA Methyltransferase with Risk of Lung Cancer in Non-Hispanic Whites
Authors: Wang Luo , Liu Hongji , Zhang Zhengdong , Spitz Margaret R. , Wei Qingyi
Published: December 2006

O 6-methylguanine, a methylated damage lesion in DNA, correlates with spontaneous G:C → A:T transition mutations and leads to activation of oncogene K-ras or dysfunction of the tumor suppressor gene p53. O6-methylguanine-DNA methyltransferase (MGMT) is critical for repairing damage to the O6-position of guanine. Therefore, we tested our hypothesis that genetic variants of MGMT are associated with increased lung cancer risk in a Caucasian population of 1,121 lung cancer patients and 1,163 matched cancer-free controls. We genotyped four potentially functional single nucleotide polymorphisms (SNPs) of MGMT: exon 3 codon 84C → T (L84F), exon 5 codon 143A → G (I143V), and two promoter SNPs 135G → T and 485C → A. The allele frequency distributions of the SNPs of codon 84C → T and the promoter 135G → T in the cases were borderline different from that in the controls. After defining the minor allele (T for codon 84C → T and G for codon 143A → G) as the variant allele, we categorized the MGMT genotypes as either 0 variants (84CC-143AA) or 1-4 variants. Compared with 0 variants, those with 1-4 variants showed a statistically significantly increased risk of lung cancer (P = 0.040). Further stratification analysis showed that this increased risk was more pronounced in women, current smokers, and non–small cell lung cancer. We did not find any association between the MGMT promoter SNPs and lung cancer risk. Our findings suggest that non-synonymous SNPs in MGMT are associated with modestly increased risk of lung cancer in Caucasians and need to be further investigated. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2364–9)
Lead, Genetic Susceptibility, and Risk of Adult Brain Tumors
Authors: Rajaraman Preetha , Stewart Patricia A. , Samet Jonathan M. , Schwartz Brian S. , Linet Martha S. , Zahm Shelia Hoar , Rothman Nathaniel , Yeager Meredith , Fine Howard A. , Black Peter M. , Loeffler Jay , Shapiro William R. , Selker Robert G. , Inskip Peter D.
Published: December 2006

Background: Although few etiologic factors for brain tumors have been identified, limited data suggest that lead may increase the risk of brain tumors, particularly meningioma. The ALAD G177C polymorphism affects the toxicokinetics of lead and may confer genetic susceptibility to adverse effects of lead exposure.

Methods: We examined occupational exposure to lead and risk of brain tumors in a multisite, hospital-based, case-control study of 489 patients with glioma, 197 with meningioma, and 799 non-cancer controls frequency matched on hospital, age, sex, race/ethnicity, and residential proximity to hospital. ALAD genotype was assessed by a Taqman assay for 355 glioma patients, 151 meningioma patients, and 505 controls. Exposure to lead was estimated using a rigorous questionnaire-based exposure assessment strategy incorporating lead measurement and other occupational data abstracted from published articles and reports.

Results: Increased risk of meningioma with occupational lead exposure (estimated by odds ratios and 95% confidence intervals) was most apparent in individuals with the ALAD2 variant allele, for whom risk increased from 1.1 (0.3-4.5) to 5.6 (0.7-45.5) and 12.8 (1.4-120.8) for estimated cumulative lead exposures of 1 to 49 μg/m3-y, 50 to 99 μg/m3-y, and ≥100 μg/m3-y, respectively, compared with unexposed individuals (two-sided P trend = 0.06). This relationship became stronger after excluding occupational lead exposures characterized by a low confidence level or occurring in the 10 years before meningioma diagnosis. Occupational lead exposure was not associated with glioma risk.

Conclusions: Although our results indicate that lead may be implicated in meningioma risk in genetically susceptible individuals, these results need to be interpreted with caution given the small numbers of exposed cases with a variant genotype. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2514–20)
Risk Factors for Hormone Receptor-Defined Breast Cancer in Postmenopausal Women
Authors: Rosenberg Lena U. , Einarsdóttir Kristjana , Friman Erika Isaksson , Wedrén Sara , Dickman Paul W. , Hall Per , Magnusson Cecilia
Published: December 2006

The effect of classic breast cancer risk factors on hormone receptor-defined breast cancer is not fully clarified. We explored these associations in a Swedish population-based study. Postmenopausal women ages 50 to 74 years, diagnosed with invasive breast cancer during 1993 to 1995, were compared with 3,065 age frequency-matched controls. We identified 332 estrogen receptor (ER−) and progesterone receptor (PR−) negative, 286 ER+PR−, 71 ER−PR+, 1,165 ER+PR+, and 789 tumors with unknown receptor status. Unconditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (95% CI). Women ages ≥30 years, compared with those ages 20 to 24 years at first birth, were at an increased risk of ER+PR+ tumors (OR, 1.5; 95% CI, 1.2-1.8) but not ER−PR− tumors (OR, 1.1; 95% CI, 0.8-1.6). Women who gained ≥30 kg in weight during adulthood had an ∼3-fold increased relative risk of ER+PR+ tumors (OR, 2.7; 95% CI, 1.9-3.8), but no risk increase of ER−PR− tumors (OR, 1.0; 95% CI, 0.5-2.1), compared with women who gained <10 kg. Compared with never users, women who used menopausal estrogen-progestin therapy for at least 5 years were at increased risk of ER+PR+ tumors (OR, 3.0; 95% CI, 2.1-4.1) but not ER−PR− tumors (OR, 1.3; 95% CI, 0.7-2.5). In conclusion, other risk factors were similarly related to breast cancer regardless of receptor status, but high age at first birth, substantial weight gain in adult age, and use of menopausal estrogen-progestin therapy were more strongly related to receptor-positive breast cancer than receptor-negative breast cancer. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2482–8)
Nonsynonymous Polymorphisms in Genes in the One-Carbon Metabolism Pathway and Associations with Colorectal Cancer
Authors: Koushik Anita , Kraft Peter , Fuchs Charles S. , Hankinson Susan E. , Willett Walter C. , Giovannucci Edward L. , Hunter David J.
Published: December 2006

The Ala222Val single nucleotide polymorphism (SNP) in the gene for 5,10-methylenetetrahydrofolate reductase (MTHFR), a critical enzyme in one-carbon metabolism, has been associated with colorectal cancer risk. Many enzymes are involved in one-carbon metabolism, and SNPs in the corresponding genes may play a role in colorectal carcinogenesis. We examined 24 nonsynonymous SNPs in 13 genes involved in the one-carbon metabolism pathway in relation to the risk of colorectal cancer in a case-control study nested in the Nurses' Health Study and the Health Professionals Follow-up Study cohorts. Among 376 men and women with colorectal cancer and 849 controls, a reduced risk of colorectal cancer was observed for Val/Val versus Ala carriers of MTHFR Ala222Val [odds ratio (OR), 0.66; 95% confidence interval (CI), 0.43-1.00]. An increased risk was suggested for the variant carrier genotypes versus homozygous wild-type for betaine hydroxymethyltransferase Arg239Gln (OR, 1.40; 95% CI, 1.07-1.83) and two linked SNPs in methionine synthase reductase, Ser284Thr (OR, 1.85; 95% CI, 1.05-3.27) and Arg415Cys (OR, 2.03; 95% CI, 1.15-3.56). The other SNPs were not associated with colorectal cancer risk. Also, none of the SNPs were associated with risk in subgroups of dietary methyl status or were jointly associated with colorectal cancer risk in combination with another SNP, except possibly SNPs in methionine synthase and transcobalamin II. However, these analyses of gene-diet interactions were limited in statistical power. Our results corroborate previous findings for MTHFR Ala222Val and suggest that other genes involved in one-carbon metabolism, particularly those that affect DNA methylation, may be associated with colorectal cancer risk. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2408–17)
Ectopic Granule Cells of the Rat Dentate Gyrus
Authors: Scharfman Helen , Goodman Jeffrey , McCloskey Daniel
Published: December 2006

Granule cells of the mammalian dentate gyrus normally form a discrete layer, and virtually all granule cells migrate to this location. Exceptional granule cells that are positioned incorrectly, in ‘ectopic’ locations, are rare. Although the characteristics of such ectopic granule cells appear similar in many respects to granule cells located in the granule cell layer, their rare occurrence has limited a full evaluation of their structure and function. More information about ectopic granule cells has been obtained by studying those that develop after experimental manipulations that increase their number. For example, after severe seizures, the number of ectopic granule cells located in the hilus increases dramatically. These experimentally-induced ectopic granule cells may not be equivalent to normal ectopic granule cells necessarily, but the vastly increased numbers have allowed much more information to be obtained. Remarkably, the granule cells that are positioned ectopically develop intrinsic properties and an axonal projection that are similar to granule cells that are located normally, i.e., in the granule cell layer. However, dendritic structure and synaptic structure/function appear to differ. These studies have provided new insight into a rare type of granule cell in the dentate gyrus, and the plastic characteristics of dentate granule cells that appear to depend on the location of the cell body.
Bisphosphonate-Associated Osteonecrosis of the Jaw in Patients with Multiple Myeloma and Breast Cancer
Authors: Nastro E. , Musolino C. , Allegra A. , Oteri G. , Cicciù M. , Alonci A. , Quartarone E. , Alati C. , De Ponte F.S.
Published: December 2006

Osteonecrosis of the jaw is an unremitting adverse outcome associated with bisphosphonate therapy in patients with multiple myeloma or bone metastases from solid tumors. Twelve patients who presented with exposed bone associated with bisphosphonates were reviewed to determine the type, dosage and duration of their bisphosphonate therapy, presenting findings, comorbidities and the event that incited the bone exposure. The discontinuation of bisphosphonate therapy has not helped reverse the presence of osteonecrosis, and the surgical manipulation of the involved site appears to worsen the underlying bone pathology. Hyperbaric oxygen, which has proven efficacious in other forms of osteonecrosis by establishing an oxygen gradient, is of no definitive benefit to patients with bisphosphonate-induced exposed bone. Antibiotic therapy is useful in controlling pain and swelling but ineffective in preventing the progression of the exposed bone. To date, prevention is the only currently possible therapeutic approach to the management of this complication.
The Spark of Life: The Role of Electric Fields in Regulating Cell Behaviour Using the Eye as a Model System
Authors: Forrester John V. , Lois Noemi , Zhao Min , McCaig Colin
Published: December 2006

Endogenous electric fields (EF) have long been known to influence cell behaviour during development, neural cell tropism, wound healing and cell behaviour generally. The effect is based on short circuiting of electrical potential differences across cell and tissue boundaries generated by ionic segregation. Recent in vitro and in vivo studies have shown that EF regulate not only cell movement but orientation of cells during mitosis, an effect which may underlie shaping of tissues and organs. The molecular basis of this effect is founded on receptor-mediated cell signalling events and alterations in cytoskeletal function as revealed in studies of gene deficient cells. Remarkably, not all cells respond directionally to EF in the same way and this has consequences, for instance, for lens development and vascular remodelling. The physical basis of EF effect may be related to changes induced in ‘bound water’ at the cell surface, whose organisation in association with trans-membrane proteins (e.g. receptors) is disrupted when EF are generated.
Preoperative Bowel Preparation: Surgical Standard or Past?
Authors: Müller-Stich Beat P. , Choudhry Arash , Vetter Gregor , Antolovic Dalibor , Mehrabi Arianeb , Köninger Jörg , Weitz Jürgen , Büchler Markus W. , Gutt Carsten N.
Published: December 2006

Background: Preoperative bowel preparation is still routinely used prior to colorectal surgery. This concept is based on traditional and personal empiricism and usually not evidence based. The objective of the present review was to reassess this dogma against the background of the highest level of evidence published thus far. Methods: The Medline database was searched using the search terms ‘preoperative’, ‘bowel’ and ‘preparation’ limited to ‘randomized controlled trials’ and ‘meta-analyses’. Ten randomised controlled trials and seven meta-analyses comparing orthograde bowel cleansing to no preoperative bowel preparation were considered for rates of anastomotic leakages, surgical infections and other types of complications, reoperations and mortality. Results: All the most recent meta-analyses showed a significant increase of anastomotic dehiscences in patients with preoperative orthograde bowel cleansing. Additionally, a trend towards higher rates of surgical infectious complications and re-operations was revealed. Mortality remained unchanged by preoperative orthograde bowel cleansing. Conclusion: Routine preoperative orthograde bowel cleansing is no longer justified prior to colorectal surgery in general due to increased risk of anastomotic leakages. Further investigations should focus on different types of bowel preparation in situations where preoperative bowel preparation still may have a role such as total mesorectal resection with low anastomosis and protective ileostomy.
Institutional Design for EMS-Based Government Procurement Policies
Authors: Potoski Matthew , Prakash Aseem
Published: December 2006

In recent years scholars have highlighted the public policy potential of using voluntary programs based on environmental management systems (EMS) to improve firms' environmental and regulatory performance. While firms receive some benefits for joining EMS-based voluntary programs, these incentives could be strengthened if governments mandated joining such programs as a precondition for participating in government procurement. While we support Arnold and Whitford's proposal to use public procurement eligibility criteria to induce firms to take environmentally progressive action, we have concerns about using any EMS or EMS-based voluntary program for these purposes. EMS-based programs must impose real requirements on firms and must have in place monitoring systems to ensure that such requirements are met. Only then will EMSprograms likely be effective as well as credible with stakeholders.
Inquisitorial Ideology at Work in an Auto De Fe, 1680: Religion in the Context of Proto-Racism
Authors: Graizbord David
Published: December 2006

The article explores inquisitorial ideology as functionaries of the Spanish Inquisition represented and understood it in the late seventeenth century. My analysis focuses on the official account of and sermon delivered at a monumental auto de fe celebrated in Madrid in 1680. I contend that in the process of demonizing Jews and Judaism, the auto articulated a religious worldview with deep roots in a society not yet "disenchanted" by modernity. My attempt, here, however, is also to anchor an interpretation of the auto in its unique historical context—a context of anti-Portuguese persecution in late seventeenth-century Spain—and thus to historicize more sweeping, anthropological readings of auto ceremonies as forms of religious representation (for instance, in recent work by Maureen Flynn), while deepening interpretations of inquisitorial Judeophobia (such as that of Marvin Lunenfeld) that emphasize the socio-political dynamics of "scapegoating" rather than anti-Judaism's preponderant religious dimension.
Proportionality in Sweden: The Influence of European Law
Authors: Groussot Xavier
Published: December 2006

The principle of proportionality constitutes a complex principle that could be seen as the keystone of the general principles of Community law and ECHR. The aim of this article is to demonstrate the influence of European Community (EC) law and the European Convention of Human Rights (ECHR) on the definition and application of the principle of proportionality in Swedish public law from 1996 to 2006. The Supreme Administrative Court has given some indications as to the application of the principle of proportionality, notably as to the importance of the balancing of interests. Interestingly, this Court has also been proactive as to the application of the principle of proportionality in internal law, e.g. concerning environmental law, tax law, administrative licenses. Moreover, the principle has influenced national legislation in many fields. It is argued, finally, that these jurisprudential and legislative developments increase the judicial protection of the individual and also modifies the structure of traditional judicial review by attributing a new role to Swedish national courts.
Creating Pseudo–Forecast Ensembles Statistically Using a Characterization of Displacements: A Pilot Study
Authors: Nehrkorn Thomas , Hoffman Ross N.
Published: December 2006

A feature-based statistical method is investigated as a method of generating pseudoensembles of numerical weather prediction forecasts. The goal is to enhance or dress a single dynamical forecast or an ensemble of dynamical forecasts with many realistic perturbations so as to represent better the forecast uncertainty. The feature calibration and alignment method (FCA) is used to characterize forecast differences and to generate the additional ensemble members. FCA is unique in decomposing forecast errors or differences into phase, bias, and residual error or difference components. In a pilot study using 500-hPa geopotential height data, pseudoensembles of weather forecasts are generated from one deterministic forecast and perturbations obtained by randomly sampling FCA displacements based on a priori statistics and applying these displacements to the original deterministic forecast. Comparison with actual dynamical ensembles of 500-hPa geopotential height generated by ECMWF show that important features of the dynamical ensemble, such as the spatial patterns of the ensemble mean and variance, can be approximated by the FCA pseudoensemble. Ensemble verification statistics are presented for the dynamic and FCA ensemble and compared with those of simpler statistically based pseudoensembles. Some limitations of the FCA ensembles are noted, and mitigation approaches are discussed, with a view toward applying the method to mesoscale forecasts for dispersion modeling.
The Temporal Variability of Soil Moisture and Surface Hydrological Quantities in a Climate Model
Authors: Arora Vivek K. , Boer George J.
Published: December 2006

The variance budget of land surface hydrological quantities is analyzed in the second Atmospheric Model Intercomparison Project (AMIP2) simulation made with the Canadian Centre for Climate Modelling and Analysis (CCCma) third-generation general circulation model (AGCM3). The land surface parameterization in this model is the comparatively sophisticated Canadian Land Surface Scheme (CLASS). Second-order statistics, namely variances and covariances, are evaluated, and simulated variances are compared with observationally based estimates. The soil moisture variance is related to second-order statistics of surface hydrological quantities. The persistence time scale of soil moisture anomalies is also evaluated.

Model values of precipitation and evapotranspiration variability compare reasonably well with observationally based and reanalysis estimates. Soil moisture variability is compared with that simulated by the Variable Infiltration Capacity-2 Layer (VIC-2L) hydrological model driven with observed meteorological data. An equation is developed linking the variances and covariances of precipitation, evapotranspiration, and runoff to soil moisture variance via a transfer function. The transfer function is connected to soil moisture persistence in terms of lagged autocorrelation. Soil moisture persistence time scales are shorter in the Tropics and longer at high latitudes as is consistent with the relationship between soil moisture persistence and the latitudinal structure of potential evaporation found in earlier studies. In the Tropics, although the persistence of soil moisture anomalies is short and values of the transfer function small, high values of soil moisture variance are obtained because of high precipitation variability. At high latitudes, by contrast, high soil moisture variability is obtained despite modest precipitation variability since the persistence time scale of soil moisture anomalies is long. Model evapotranspiration estimates show little variability and soil moisture variability is dominated by precipitation and runoff, which account for about 90% of the soil moisture variance over land surface areas.
Studies of El Niño and Interdecadal Variability in Tropical Sea Surface Temperatures Using a Nonnormal Filter
Authors: Penland Cécile , Matrosova Ludmila
Published: December 2006

A dynamically based filter is used to separate tropical sea surface temperatures (SSTs) into three components: the evolving El Niño signal, the global tropical trend, and the background. The components thus isolated are not independent. On the contrary, this procedure allows us to see the importance of the interdecadal signal to the predictability of El Niño.

The data filtered in this way reveal El Niño signals in the equatorial Indian Ocean and in the north tropical Atlantic Ocean that are remarkably similar. A signature of El Niño in the south tropical Atlantic leads Niño-3.4 SST anomalies by about 9 months. The time series of a global tropical trend is found to have a very smooth parabolic structure. In unfiltered data, this trend conspires with El Niño to obscure a meridional tropical Atlantic dipole, which is significant in the filtered background SST data.
The Link Between the Fiber Contact Zone and the Physical Properties of Paper: A Way to Control Paper Properties
Authors: Torgnysdotter Annsofie , Kulachenko Artem , Gradin Per , Wågberg Lars
Published: December 2006

Paper is a composite of fibers, air and additives where the fiber/fiber joints keep the network structure together. A study was undertaken to establish the link between the properties of the contact zone between fibers and paper performance under mechanical loading. The contact zone between fibers was investigated using light microscopy. A staining technique was developed for evaluating the influence of surface charge on fiber/fiber joint strength. The joint strength was linearly correlated with paper tensile strength and with the average amplitude of the acoustic events measured by acoustic emission testing. The fiber surface conformability was improved by changing the surface charge. This resulted in increased fiber/fiber joint strength as the relative contact area became larger. Increasing the molecular adhesion in the contact zone with the aid of strength additives also improved the fiber/fiber joint strength.
Sustainable Community for Sustainable Development
Authors: Schmidt Ella
Published: December 2006

This article analyzes the role that communal values and structures play in facilitating women's ability to cope with the economic uncertainties brought about by the large-scale emigration of men from their communities. By focusing on a women's producer cooperative among the indigenous Hñähñu people in the state of Hidalgo, Mexico, the article reveals how the members of this cooperative have responded to global forces in local ways that allow them to preserve their communal ties and even strengthen their position in their indigenous community, while at the same time selectively appropriating ‘modern’ elements of technology, international marketing, and banking.
Theoretical and Conceptual Notes Concerning Transference and Countertransference Processes in Groups and by Groups, and the Social Unconscious: Part I
Authors: Hopper Earl
Published: December 2006

In this article I will outline the main theories and conceptualisations of transference and countertransference in groups and by groups, and the social unconscious. I am increasingly convinced that working in and with transference and countertransference processes is vital to the clinical project, and that taking a ‘relational’ perspective is essential to this. Based on a monograph that I am writing about transference and countertransference processes, these notes are not new, but I hope that they will be useful, especially to students and younger colleagues. In Part I, I will consider transference and countertransference processes by individual persons in groups, and in Part II, to be published in March 2007, transference processes by groups of persons. In Part III, to be published in June 2007, I will summarise a few points about the theory and concept of the social unconscious, focusing on the effects of the social unconscious on transference and countertransference processes.
The Only One
Authors: MacDonald Pat
Published: December 2006

In this article, I set down some of my experiences as the only white member in a group which was set up to discuss and to work on racial differences. I experienced a frightening sense of exclusion and working through difficult feelings in the group led me to an understanding of the discrimination black people encounter in their everyday lives. Many of my emotions and reactions I found echoed in those of the black African writer Frantz Fanon.
Extreme Right Movements
Authors: Orfali Birgitta
Published: December 2006

In order to understand how and why extreme right parties and movements are more often put forward in the political sphere and taken up by the media, I address a social psychological perspective and consider the many processes at work in these phenomena. Starting with the explanation of the success of the extreme right in terms of the theory of innovation, I analyse its acceptance through the theory of social representations. A dynamic social psychology has to focus on social change and conflict, especially in political topics and communication.
Introduction: Reclaiming theSocialin Social Psychology
Authors: Stam Henderikus J.
Published: December 2006

The articles in this special issue cover a range of critical issues and approaches in social psychology. Two of their common features are: (a) their restatement—in various forms—of the unresolved epistemological problems that continue to inform critical discussions of social psychology; and (b) the rarely debated question of just what makes social psychology social. These two questions are interlocking: the undecided nature of the latter eventually creates an impassable barrier to resolving the former. Focusing on a cross-section of issues derived from the social psychology literature presented in this issue, I introduce the problematic and contested nature of the domain of social psychology.
The As If in Cognitive Science, Neuroscience and Anthropology
Authors: Adenzato Mauro , Garbarini Francesca
Published: December 2006

In recent years, neurophysiological and psychological research has highlighted a pragmatic version of the theory of knowledge, a version in which the concept of simulation has been found to play a crucial role. In fact, research on canonical and mirror neurons has shown that an as if simulative schema is required to perceive, categorize and understand the meaning of the external world. The present study compares the cognitive paradigm of embodied cognition with Pierre Bourdieu’s practice theory. Specifically, cognitive processes and cultural mechanisms are described as phenomena that emerge from the dynamic interaction that exists between people’s practical abilities and the structure of the local environment in which they act and live. A pragmatic conception of knowledge has also emerged in the field of ethnological investigation. Indeed, the concepts of resonance and empathy have proven to be essential instruments for ethnological knowledge.