bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adenovirus Type 5 Early Region 1B 156R Protein Promotes Cell Transformation Independently of Repression of p53-Stimulated Transcription
Authors: Sieber Timo , Dobner Thomas 
Published: December 2006

ABSTRACT
Early region 1B (E1B) of adenovirus type 5 (Ad5) encodes at least five different polypeptides generated by alternative splicing of a common mRNA precursor. Two of these gene products, E1B-19K and E1B-55K, are individually capable of cooperating with the Ad5 E1A proteins to completely transform rodent cells in culture. Substantial evidence suggests that these two E1B proteins contribute to cell transformation by antagonizing growth arrest and apoptosis. Here, we performed genetic and biochemical analyses to assess the attributes of the remaining E1B proteins (E1B-156R, E1B-93R, and E1B-84R). Our results show that E1B-156R, which comprises the 79 amino-terminal and 77 carboxy-terminal amino acids of E1B-55K, also enhances focal transformation of primary rat cells in cooperation with E1A. Since E1B-156R seemed unable to relocalize p53 and inhibit its transactivating function, it must be assumed that it contributes to transformation independently of repression of p53-stimulated transcription. Furthermore, we discovered that E1B-156R contains a functional transcriptional repression domain and binds Ad5 E4orf6 and the cellular apoptosis regulator Daxx. While the ability to bind E4orf6 could indicate further biological functions of E1B-156R in viral infection, the interaction with Daxx might also be linked to its transforming potential. Taken together, these analyses introduce E1B-156R as a novel transformation-promoting E1B protein that acts without repressing p53 transactivation. Moreover, identification of the interaction partners E4orf6 and Daxx provides a first glance of E1B-156R's potential functions.
Glycoprotein L Disruption Reveals Two Functional Forms of the Murine Gammaherpesvirus 68 Glycoprotein H
Authors: Gillet Laurent , May Janet S. , Colaco Susanna , Stevenson Philip G. 
Published: December 2006

ABSTRACT
The herpesvirus glycoprotein H (gH) and gL associate to form a heterodimer that plays a central role in virus-driven membrane fusion. When archetypal alpha- or betaherpesviruses lack gL, gH misfolds and progeny virions are noninfectious. In order to define the role that gL plays in gamma-2 herpesvirus infections, we disrupted its coding sequence in murine gammaherpesvirus-68 (MHV-68). MHV-68 lacking gL folded gH into a conformation antigenically distinct from the form that normally predominates on infected cells. gL-deficient virions bound less well than the wild type to epithelial cells and fibroblasts. However, they still incorporated gH and remained infectious. The cell-to-cell spread of gL-deficient viruses was remarkably normal, as was infection, dissemination, and latency establishment in vivo. Viral membrane fusion was therefore gL independent. The major function of gL appeared to be allowing gH to participate in cell binding prior to membrane fusion. This function was most important for the entry of MHV-68 virions into fibroblasts and epithelial cells.
M135R Is a Novel Cell Surface Virulence Factor of Myxoma Virus
Authors: Barrett John W. , Sypula Joanna , Wang Fuan , Alston Lindsay R. , Shao Zhuhong , Gao Xiujuan , Irvine Timothy S. , McFadden Grant 
Published: December 2006

ABSTRACT
Myxoma virus (MV) encodes a cell surface protein (M135R) that is predicted to mimic the host alpha/beta interferon receptor (IFN-α/β-R) and thus prevent IFN-α/β from triggering a host antiviral response. This prediction is based on sequence similarity to B18R, the viral IFN-α/β-R from vaccinia virus (VV), which has been demonstrated to bind and inhibit type I interferons. However, M135R is only half the size of VV B18R. All other poxvirus-encoded IFN-α/β-R homologs align only to the amino-terminal half of M135R. Peptide antibodies raised against M135R were used for immunoblotting and immunofluorescence and indicate that M135R is expressed as an early gene and that the product is a cell surface N-linked glycoprotein that is not secreted. In contrast to the predicted properties of M135R as an inhibitor of type I interferon, all binding and inhibition assays designed to demonstrate whether M135R can interact with IFN-α/β have been negative. However, pathogenesis studies with a targeted M135-knockout MV construct (vMyx135KO) indicate that the deletion of M135R severely attenuates MV pathogenesis in the European rabbit. We propose that M135R is an important immunomodulatory virulence factor for myxomatosis but that the target immune ligand is not from the predicted type I interferon family and remains to be identified.
Control of Simian Immunodeficiency Virus SIVmac239 Is Not Predicted by Inheritance of
Mamu-B
*
17
-Containing Haplotypes
Authors: Wojcechowskyj Jason A. , Yant Levi J. , Wiseman Roger W. , O'Connor Shelby L. , O'Connor David H. 
Published: December 2006

ABSTRACT

It is well established that host genetics, especially major histocompatibility complex (MHC) genes, are important determinants of human immunodeficiency virus disease progression. Studies with simian immunodeficiency virus (SIV)-infected Indian rhesus macaques have associated
Mamu-B
*
17
with control of virus replication. Using microsatellite haplotyping of the 5-Mb MHC region, we compared disease progression among SIVmac239-infected Indian rhesus macaques that possess
Mamu-B
*
17
-containing MHC haplotypes that are identical by descent. We discovered that SIV-infected animals possessing identical
Mamu-B
*
17
-containing haplotypes had widely divergent disease courses. Our results demonstrate that the inheritance of a particular
Mamu-B
*
17
-containing haplotype is not sufficient to predict SIV disease outcome.
Simian Immunodeficiency Virus SIVmac239 Infection of Major Histocompatibility Complex-Identical Cynomolgus Macaques from Mauritius
Authors: Wiseman Roger W. , Wojcechowskyj Jason A. , Greene Justin M. , Blasky Alex J. , Gopon Tobias , Soma Taeko , Friedrich Thomas C. , O'Connor Shelby L. , O'Connor David H. 
Published: December 2006

ABSTRACTNonhuman primates are widely used to study correlates of protective immunity in AIDS research. Successful cellular immune responses have been difficult to identify because heterogeneity within macaque major histocompatibility complex (MHC) genes results in quantitative and qualitative differences in immune responses. Here we use microsatellite analysis to show that simian immunodeficiency virus (SIV)-susceptible cynomolgus macaques (Macaca fascicularis) from the Indian Ocean island of Mauritius have extremely simple MHC genetics, with six common haplotypes accounting for two-thirds of the MHC haplotypes in feral animals. Remarkably, 39% of Mauritian cynomolgus macaques carry at least one complete copy of the most frequent MHC haplotype, and 8% of these animals are homozygous. In stark contrast, entire MHC haplotypes are rarely conserved in unrelated Indian rhesus macaques. After intrarectal infection with highly pathogenic SIVmac239 virus, a pair of MHC-identical Mauritian cynomolgus macaques mounted concordant cellular immune responses comparable to those previously reported for a pair of monozygotic twins infected with the same strain of human immunodeficiency virus. Our identification of relatively abundant SIV-susceptible, MHC-identical macaques will facilitate research into protective cellular immunity.
Role for Nonstructural Protein 1 of Severe Acute Respiratory Syndrome Coronavirus in Chemokine Dysregulation
Authors: Law Anna H. Y. , Lee Davy C. W. , Cheung Benny K. W. , Yim Howard C. H. , Lau Allan S. Y. 
Published: December 2006

ABSTRACT
Severe acute respiratory syndrome (SARS) is an emerging infectious disease caused by a novel coronavirus. Since its associated morbidity and mortality have been postulated to be due to immune dysregulation, we investigated which of the viral proteins is responsible for chemokine overexpression. To delineate the viral and cellular factor interactions, the role of four SARS coronavirus proteins, including nonstructural protein 1 (nsp-1), nsp-5, envelope, and membrane, were examined in terms of cytokine induction. Our results showed that the SARS coronavirus nsp-1 plays an important role in CCL5, CXCL10, and CCL3 expression in human lung epithelial cells via the activation of NF-κB.
Toxicant Exposure in Cigarette Reducers versus Light Smokers
Authors: Hatsukami Dorothy K. , Le Chap T. , Zhang Ying , Joseph Anne M. , Mooney Marc E. , Carmella Steven G. , Hecht Stephen S. 
Published: December 2006

Abstract
Background: The extent of exposure to tobacco toxicants in smokers who have reduced their cigarette intake compared with smokers who are light smokers is relatively unknown. The goal of this study is to investigate the occurrence of compensatory smoking in reducers compared with light smokers by measuring toxicant exposure.
Methods: Participants in two smoking reduction intervention studies (N = 64) were selected for comparison with a group of light smokers (N = 62) who smoked the same number of cigarettes as the reducers. A compensatory smoking score was defined (biomarker level for reducer/biomarker level for light smoker) and calculated for urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronides (total NNAL), metabolites of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-I-(3-pyridyl)-1-butanone, to measure the degree of smoking compensation in reducers when compared with the light smokers.
Results: The mean level of creatinine-adjusted total NNAL for reducers was over twice that of light smokers even when they smoked about the same number of cigarettes per day. The difference of the mean total NNAL concentrations between light smokers and reducers was highly significant (P &lt; 0.0001). Wide variability in total NNAL concentrations was also observed in reducers, with the extent of this variability between light smokers and reducers being significantly different (P = 0.0005). The level of individual reduction was shown to be a consistent predictor of compensatory smoking (r = 0.50; adjusted Ps = 0.002), with greater cigarette reduction associated with more compensation.
Conclusions: Compensatory smoking limits the harm reduction value of decreased smoking of cigarettes. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2355–8)
Mass Spectrometric Quantitation of Nicotine, Cotinine, and 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanol in Human Toenails
Authors: Stepanov Irina , Feuer Rachel , Jensen Joni , Hatsukami Dorothy , Hecht Stephen S. 
Published: December 2006

Abstract
Numerous studies have quantified total cotinine (the sum of cotinine and cotinine-N-glucuronide) and total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol [NNAL; the sum of NNAL and its O- and N-glucuronides (NNAL-Glucs)] in the urine and blood of smokers, smokeless tobacco users, and nonsmokers exposed to environmental tobacco smoke. Analysis of hair and nails has several advantages over blood and urine testing, such as accumulation of xenobiotics during long-term exposure, ease of collection, and indefinite stability of samples. We developed sensitive methods for quantitation of nicotine, cotinine, and NNAL in human toenails. Nicotine and cotinine were analyzed by gas chromatography-mass spectrometry-selected ion monitoring. NNAL was assayed using liquid chromatography-electrospray ionization-tandem mass spectrometry-selected reaction monitoring. The detection limits of the methods were 0.01 ng/mg toenail for nicotine, 0.012 ng/mg toenail for cotinine, and 0.02 pg/mg toenail for NNAL. In 35 smokers, the mean nicotine level was 5.9 ± 5.6 ng/mg toenail, mean cotinine was 1.6 ± 1.3 ng/mg toenail, and mean NNAL was 0.41 ± 0.67 pg/mg toenail. Samples collected from six nonsmokers were negative for NNAL. In smokers, NNAL correlated with cotinine (r = 0.77; P &lt; 0.0001). The results of this study for the first time show the presence of cotinine and NNAL in human toenails. These sensitive and quantitative methods should be useful in epidemiologic studies of the role of chronic tobacco smoke exposure, including environmental tobacco smoke exposure, in human cancer. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2378–83)
Cancer Incidence and Mortality and Vitamin D in Black and White Male Health Professionals
Authors: Giovannucci Edward , Liu Yan , Willett Walter C. 
Published: December 2006

Abstract
Blacks have been documented to have low vitamin D levels. We thus examined whether total cancer incidence and mortality rates differ between Blacks and Whites in a population of male health professionals, and particularly for digestive system cancers (oral, esophagus, stomach, pancreas, and colorectum), which have been most consistently linked to poor vitamin D status. Second, we examined whether Blacks might be more susceptible to these cancers if they concurrently had other risk factors for hypovitaminosis D. In the Health Professionals Follow-up Study, from 1986 to 2002, 99 of 481 Black men and 7,019 of 43,468 White men were diagnosed with cancer. Adjusting for multiple dietary, lifestyle, and medical risk factors, using Cox modeling, Black men were at higher risk of total cancer incidence [relative risk (RR), 1.32; 95% confidence interval (95% CI), 1.08-1.61; P = 0.007] and total cancer mortality (RR, 1.89; 95% CI, 1.40-2.56; P &lt; 0.0001) and especially digestive system cancer mortality (RR, 2.24; 95% CI, 1.35-3.70). Compared with Whites with relatively few risk factors for hypovitaminosis D, Blacks also with few risk factors for hypovitaminosis D were not at appreciably higher risk of total cancer incidence (RR, 0.95; 95% CI, 0.60-1.51) or mortality (RR, 1.55; 95% CI, 0.91-2.62), but Black men with additional risk factors for poorer vitamin D status had a much higher cancer incidence (RR, 1.57; 95% CI, 1.16-2.11) and mortality risk (RR, 2.27; 95% CI, 1.57-3.28). This pattern was even more pronounced for digestive system cancer. Our results suggest that the high frequency of hypovitaminosis D in Blacks may be an important, and easily modifiable, contributor to their higher risk of cancer incidence and mortality. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2467–72)
Usefulness of Body Mass Index as a Sufficient Adiposity Measurement for Sex Hormone Concentration Associations in Postmenopausal Women
Authors: Mahabir Somdat , Baer David J. , Johnson Laura L. , Hartman Terry J. , Dorgan Joanne F. , Campbell William S. , Clevidence Beverly A. , Taylor Philip R. 
Published: December 2006

Abstract
Background: Both obesity and sex hormones are known risk factors for postmenopausal breast cancer. Although adiposity and sex hormones have been studied in the past, previous reports in postmenopausal women have not been conducted under carefully controlled dietary conditions. In this study, we investigated the usefulness of body mass index (BMI) as a sufficient adiposity measurement to assess associations with sex hormone levels.
Methods: This study was conducted as a cross-sectional analysis within the control segment (0 g alcohol group) of a randomized, crossover design, in which 51 postmenopausal women consumed 0 (control), 15 (one drink), and 30 (two drinks) g alcohol (ethanol)/d for 8 weeks each as part of a controlled diet. Dual-energy X-ray absorptiometry scans were administered to the women during the control (0 g alcohol) segment, and a blood sample was drawn at the end of that diet period for hormone analysis.
Results: In multivariate analysis (adjusted for age, race, family history of breast cancer, parity, and menarche &lt;12 years), women who were overweight or obese had significantly higher serum concentrations of estradiol, bioavailable estradiol, estrone, and estrone sulfate and lower sex hormone-binding globulin than normal weight women (all P &lt; 0.05). In models adjusted for BMI and the covariates above, none of the dual-energy X-ray absorptiometry adiposity measures added further information (all P &gt; 0.10) for these five analytes beyond that of BMI alone.
Conclusions: In this population of postmenopausal women, under carefully controlled dietary conditions, we confirmed previous findings that higher levels of adiposity were associated with higher concentrations of estrogens and lower sex hormone-binding globulin, and we found that the use of the epidemiology-friendly BMI seems sufficient to assess associations with these hormone levels. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2502–7)
Prostate Cancer Risk in Relation to Selected Genetic Polymorphisms in Insulin-like Growth Factor-I, Insulin-like Growth Factor Binding Protein-3, and Insulin-like Growth Factor-I Receptor
Authors: Chen Chu , Freeman Robert , Voigt Lynda F. , Fitzpatrick Annette , Plymate Stephen R. , Weiss Noel S. 
Published: December 2006

AbstractWe conducted a nested case-control study within a cohort of elderly Americans to examine the role of the insulin-like growth factor (IGF) signaling pathway in prostate cancer etiology. The distribution of genotypes of IGF-I (CA)n, IGF binding protein-3 (IGFBP-3) A-202C, and of the 2-bp deletion and (AGG)n polymorphisms in IGF-I receptor (IGF-IR) was compared between men with prostate cancer (n = 213) and equal number of controls matched on year of blood draw, survival until the date of diagnosis, race, and age. Among controls, the number of CA repeats in IGF-I was not correlated to any appreciable degree with plasma IGF-I concentration, whereas the IGFBP-3 CC genotype was associated with a relatively low level of plasma IGFBP-3. There was no association between prostate cancer risk and the number of CA repeats in IGF-I, IGFBP-3 genotype, or the presence of the 2-bp deletion in IGF-IR. There was a small increased risk among men who did not carry two copies of the (AGG)7 allele of IGF-IR. These results add to the evidence that the number of IGF-I CA repeats is not associated with prostate cancer risk. Our observation that men who do not carry two copies of the IGF-IR (AGG)7 allele are at increased risk of prostate cancer merits further investigation. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2461–6)
Obesity, High Energy Intake, Lack of Physical Activity, and the Risk of Kidney Cancer
Authors: Pan Sai Yi , DesMeules Marie , Morrison Howard , Wen Shi Wu ,   The Canadian Cancer Registries Epidemiology Research Group
Published: December 2006

Abstract
The authors conducted a population-based case-control study of 810 cases with histologically confirmed incident kidney cancer and 3,106 controls to assess the effect of obesity, energy intake, and recreational physical activity on renal cell and non–renal cell cancer risk in Canada from 1994 to 1997. Compared with normal body mass index (BMI; 18.5 to &lt;25.0 kg/m2), obesity (BMI, ≥30.0 kg/m2) was associated with multivariable-adjusted odds ratios (OR) and 95% confidence intervals (95% CI) of 2.57 (2.02-3.28) for renal cell cancer and 2.79 (1.70-4.60) for non–renal cell cancer. The OR (95% CI) associated with the highest quartiles of calorie intake was 1.30 (1.02-1.66) for renal cell cancer and 1.53 (0.92-2.53) for non–renal cell cancer. Compared with the lowest quartile of total recreational physical activity, the highest quartile of total activity was associated with an OR (95% CI) of 1.00 (0.78-1.28) and 0.79 (0.46-1.36) for the two subtypes. There were no apparent differences between men and women about these associations. The influence of obesity and physical activity on the risk of renal cell and non–renal cell cancer did not change by age, whereas the effect of excess energy intake was stronger among older people. No significant effect modifications of physical activity on BMI among both genders and of energy intake on BMI among men were observed, with a synergic effect of obesity and high energy intake on renal cell cancer risk found among women. This study suggests that obesity and excess energy intake are important etiologic risk factors for renal cell and non–renal cell cancer. The role of physical activity needs further investigation. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2453–60)
A NAD(P)H:Quinone Oxidoreductase 1 Polymorphism Is a Risk Factor for Human Colon Cancer
Authors: Begleiter Asher , Hewitt Donna , Maksymiuk Andrew W. , Ross David A. , Bird Ranjana P. 
Published: December 2006

Abstract
Colon cancer is one of the most common cancers in North America and generally develops from colonic epithelial cells following initiation by carcinogens. We have shown that the phase II detoxifying enzyme, NAD(P)H:quinone oxidoreductase 1 (NQO1) contributes to the inhibition of carcinogen-induced colon cancer in rats at both the initiation and postinitiation stages. An inactivating polymorphism at base 609 of the NQO1 gene, 609C (NQO1 *1) → 609T (NQO1 *2), occurs at high frequency in the human population. Thus, we carried out a case-control study to determine if this polymorphism is associated with an increased risk of developing colon cancer. A total of 298 patients with colon cancer and 349 healthy controls matched for age, gender, and ethnic origin were enrolled in the study. There was an increased incidence of the NQO1 *2/*2 genotype in patients with colon cancer, with a gender and age-adjusted odds ratio of 2.68 (95% confidence intervals, 1.14-6.28). However, the incidence of the NQO1 *1/*2 genotype was not increased in patients with colon cancer compared with controls. When the patient and control groups were stratified by tobacco and alcohol use, the incidences of the NQO1 *2/*2 genotype were increased in patients with colon cancer for tobacco and alcohol users and nonusers, suggesting that there is no interaction between the NQO1 base 609 polymorphism and tobacco or alcohol use. These results strongly suggest that NQO1 plays a significant role in preventing the development of colon cancer, and individuals with an NQO1 *2/*2 genotype are at an increased risk of developing this disease. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2422–6)
Polymorphisms in the DNA Repair GenesXPC, XPD, andXPGand Risk of Cutaneous Melanoma: a Case-Control Analysis
Authors: Li Chunying , Hu Zhibin , Liu Zhensheng , Wang Li-E , Strom Sara S. , Gershenwald Jeffrey E. , Lee Jeffrey E. , Ross Merrick I. , Mansfield Paul F. , Cormier Janice N. , Prieto Victor G. , Duvic Madeleine , Grimm Elizabeth A. , Wei Qingyi 
Published: December 2006

AbstractSunlight causes DNA damage, including bulky lesions that are removed effectively by the nucleotide-excision repair (NER) pathway. There are at least eight core NER proteins participating in the pathway, and genetic variations in their genes may alter NER functions. We hypothesized that some NER variants are associated with risk of cutaneous melanoma. In a hospital-based case-control study of 602 non-Hispanic White patients with cutaneous melanoma and 603 age- and sex-matched cancer-free controls, we genotyped five common non-synonymous single-nucleotide polymorphisms identified to date and assessed their associations with risk of cutaneous melanoma. We found that a significantly increased risk of cutaneous melanoma was associated with XPD 751Lys/Gln [adjusted odds ratio (OR), 1.55 and 95% confidence interval (95% CI), 1.12-2.16] and XPD 751Gln/Gln (OR, 1.66; 95% CI, 1.03-2.68) genotypes compared with the XPD 751Lys/Lys genotype as well as XPD312Asp/Asn (OR, 1.54; 95% CI, 1.11-2.12) and XPD312Asn/Asn (OR, 1.75; 95% CI, 1.05-2.90) genotypes compared with the XPD 312Asp/Asp genotype. This increased risk was not observed in the other three XPC and XPG single-nucleotide polymorphisms. Moreover, the number of the observed XPD at-risk genotypes (i.e., 312Asn/Asn+Asn/Asp and 751Gln/Gln+Lys/Gln) was associated with cutaneous melanoma risk in a dose-response manner (OR, 1.47; 95% CI, 0.97-2.23 for one at-risk genotype; OR, 1.83; 95% CI, 1.29-2.61 for two at-risk genotypes; Ptrend &lt; 0.001). However, we found no evidence of any interaction between XPD genotypes with XPC and XPG genotypes or the known risk factors. We concluded that genetic variants of the XPD gene might serve as biomarkers for susceptibility to cutaneous melanoma. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2526–32)