bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of the composition of oral mucosal residual saliva with whole saliva
Authors: Lee J‐Y , Chung J‐W , Kim Y‐K , Chung S‐C , Kho H‐S 
Published: February 2007

Objective:  Compared with whole saliva, residual saliva comprising the oral mucosal film shows a high protein concentration. The purpose of this study was to compare the composition of residual saliva with unstimulated and stimulated whole saliva in normosalivators.Materials and methods:  The composition of oral mucosal residual saliva in 30 healthy individuals was investigated and compared with that of whole saliva. The concentrations of total protein, secretory immunoglobin A (sIgA), lactoferrin, total carbohydrate, and sialic acid were examined. The activities of peroxidase, lysozyme and α‐amylase were determined.Results:  Residual saliva had higher levels of total protein and carbohydrate than whole saliva, with a higher carbohydrate to protein ratio in the residual saliva suggesting that salivary glycoproteins are concentrated on the oral mucosal surface. sIgA, lactoferrin and sialic acid were present as highly concentrated forms in residual saliva. The enzymatic activity of peroxidase in residual saliva was higher than that of whole saliva.Conclusions:  These concentrated carbohydrate and antimicrobials on the oral mucosal surface work for mucosal defence and could be used for targeting sites for the delivery of therapeutic agents.
The Simultaneous Assessment of Constitutional, Behavioral, and Environmental Factors in the Development of Large Nevi
Authors: Cockburn Myles , Hamilton Ann , Mack Thomas 
Published: February 2007

Abstract
Background: The presence of large nevi (&gt;4 mm diameter) is the most important predictor of melanoma risk. We report on the simultaneous assessment of behavioral, constitutional, and environmental risk factors for the prevalence of large nevi in a population-based study of 33,305 individuals and compare those to risk factors for melanoma.
Methods: We used self-reported data from a population-based study of twins in California, assessing the prevalence of large nevi, lifetime usual sun exposure behavior and sunburn experience, skin type and color, and birthplace and recent domicile, for which we obtained estimates of potential sun exposure.
Results: Among constitutional variables, skin type (burn rather than tan) and having blond (but not red) hair color were associated with having more than three large nevi, as was Celtic ancestry. Spending more time in the sun in adulthood was inversely associated with number of large nevi, whereas spending time in the sun during weekends in childhood increased the risk of having large nevi. We observed no latitude gradient in nevi prevalence, except among those of Mediterranean ancestry (those in the South were more likely than those in the North to report large nevi).
Conclusion: The prevalence of large nevi was most readily explained by constitutional and then by behavioral variables in this study, rather than by independent variables describing an individual's opportunity for sun exposure. There seem to be independent relationships between nevi frequency and other melanoma risk factors, with the notable exceptions of skin color and red hair phenotype: implying that if these risk factors represent a genetic propensity to develop melanoma, that risk would seem to be unrelated to the development of nevi. (Cancer Epidemiol Biomarkers Prev 2007;16(2):200–07)
Evaluation of RNA Markers for Early Detection of Cervical Neoplasia in Exfoliated Cervical Cells
Authors: Steinau Martin , Rajeevan Mangalathu S. , Lee Daisy R. , Ruffin Mack T. , Horowitz Ira R. , Flowers Lisa C. , Tadros Talaat , Birdsong George , Husain Mujtaba , Kmak David C. , Longton Garry M. , Vernon Suzanne D. , Unger Elizabeth R. 
Published: February 2007

Abstract
Numerous molecular biomarkers have been suggested for early detection of cervical cancer, but their usefulness in routinely collected exfoliated cells remains uncertain. We used quantitative reverse transcription-PCR to evaluate expression of 40 candidate genes as markers for high-grade cervical intraepithelial neoplasia (CIN) in exfoliated cervical cells collected at the time of colposcopy. Samples from the 93 women with CIN3 or cancer were compared with those from 186 women without disease matched (1:2) for age, race, and high-risk human papillomavirus status. Normalized threshold cycles (Ct) for each gene were analyzed by receiver operating characteristics to determine their diagnostic performance in a split sample validation approach. Six markers were confirmed by an area under the curve &gt;0.6 in both sample sets: claudin 1 (0.75), minichromosome maintenance deficient 5 (0.71) and 7 (0.64), cell division cycle 6 homologue (0.71), antigen identified by monoclonal antibody Ki-67 (0.66), and SHC SH2-domain binding protein 1 (0.61). The sensitivity for individual markers was relatively low and a combination of five genes to a panel resulted in 60% sensitivity with 76% specificity, not positively increasing this performance. Although the results did not indicate superiority of RNA markers for cervical cancer screening, their performance in detecting disease in women referred for colposcopy suggests that the genes and pathways they highlight could be useful in alternative detection formats or in combination with other screening indicators. (Cancer Epidemiol Biomarkers Prev 2007;16(2):295–301)
The RAD51 135 G&gt;C Polymorphism Modifies Breast Cancer and Ovarian Cancer Risk in Polish BRCA1 Mutation Carriers
Authors: Jakubowska Anna , Gronwald Jacek , Menkiszak Janusz , Górski Bohdan , Huzarski Tomasz , Byrski Tomasz , Edler Lutz , Lubiñski Jan , Scott Rodney J. , Hamann Ute 
Published: February 2007

Abstract
Breast and ovarian cancer penetrance in BRCA1 mutation carriers is estimated to be between 15% and 80% by age 70 years. At present, it is not possible to predict with any certainty who is most likely to develop disease or which age it will develop. Previous studies have tried to correlate the sites of BRCA1 mutations with disease risk; however, the results have not yielded any definitive association. An alternative explanation that could account for differences in the penetrance of BRCA1 mutations is the action of modifier genes. In this study, we have investigated the role of the RAD51_135_G&gt;C polymorphism in breast and ovarian cancer case-control populations of Polish women who have been matched for BRCA1 mutation and year of birth. The results reveal that women who harbor the C allele have almost twice the reduction in breast and ovarian cancer risk compared with women who harbor only the G allele. These findings suggest that the effect of the RAD51 C allele is an important risk modifier for malignancies occurring on a background of BRCA1 mutations. In addition, we were able to show that the site of the BRCA1 mutation does not influence the effect of the RAD51 C allele, indicating that this polymorphism contributes to prevention of disease in BRCA1 carriers. In conclusion, the RAD51 C allele seems to protect against both breast and ovarian cancer in women harboring BRCA1 mutations. (Cancer Epidemiol Biomarkers Prev 2007;16(2):270–5)
A Prospective Study of Blood Selenium Levels and the Risk of Arsenic-Related Premalignant Skin Lesions
Authors: Chen Yu , Hall Marni , Graziano Joseph H. , Slavkovich Vesna , van Geen Alexander , Parvez Faruque , Ahsan Habibul 
Published: February 2007

Abstract
Arsenic exposure from drinking water is considered to be a risk factor for skin and internal cancers. Animal studies suggest a potential antagonism between arsenic and selenium in the body. We did a case-cohort analysis to prospectively evaluate the association between arsenic-related premalignant skin lesions and prediagnostic blood selenium levels in 303 cases of skin lesions newly diagnosed from November 2002 to April 2004 and 849 subcohort members randomly selected from the 8,092 participants in the Health Effects of Arsenic Longitudinal Study with available baseline blood and urine samples collected in 2000. Incidence rate ratios for skin lesions in increasing blood selenium quintiles were 1.00 (reference), 0.68 [95% confidence interval (95% CI), 0.39-1.18], 0.51 (95% CI, 0.29-0.87), 0.52 (95% CI, 0.30-0.91), and 0.53 (95% CI, 0.31-0.90). Effect estimates remained similar with adjustments for age, sex, body mass index, smoking status, excessive sunlight exposure (in men), well water arsenic concentration at baseline, and nutritional intakes of folate, iron, protein, vitamin E, and B vitamins. At any given arsenic exposure level, the risk of premalignant skin lesions was consistently greater among participants with blood selenium lower than the average level. The findings support the hypothesis that dietary selenium intake may reduce the incidence of arsenic-related premalignant skin lesions among populations exposed to arsenic exposure from drinking water. (Cancer Epidemiol Biomarkers Prev 2007;16(2):207–13)
Common Genetic Variation in TP53 Is Associated with Lung Cancer Risk and Prognosis in African Americans and Somatic Mutations in Lung Tumors
Authors: Mechanic Leah E. , Bowman Elise D. , Welsh Judith A. , Khan Mohammed A. , Hagiwara Nobutoshi , Enewold Lindsey , Shields Peter G. , Burdette Laurie , Chanock Stephen , Harris Curtis C. 
Published: February 2007

Abstract
Lung cancer is primarily caused by tobacco smoking, but susceptibility is likely modified by common genetic variation. In response to many forms of cellular stress, including DNA damage, the p53 protein functions to induce cell cycle arrest, DNA repair, senescence, or apoptosis. We hypothesized that common TP53 haplotypes modulate pathways of lung carcinogenesis and lung cancer susceptibility or prognosis. To investigate our hypothesis, 14 polymorphisms in TP53, including haplotype tagging and coding single nucleotide polymorphisms, were genotyped in two studies from the greater Baltimore, Maryland area. One study is a case-control study and the second is a case-only study for which TP53 mutational spectra data are available. African Americans with Pro-T-A-G-G haplotypes of the combined TP53 polymorphisms TP53_01 (rs1042522), TP53_65 (rs9895829), TP53_66 (rs2909430), TP53_16 (rs1625895), and TP53_11 (rs12951053) had both an increased risk for lung cancer (odds ratio, 2.32; 95% confidence interval, 1.18-4.57) and a worsened lung cancer prognosis (hazards ratio, 2.38; 95% confidence interval, 1.38-4.10) compared with those with Arg-T-A-G-T haplotypes. No associations of TP53 polymorphisms with lung cancer were observed in Caucasians. In the case-only study, several polymorphisms in TP53 and TP53 haplotypes, overlapping regions of TP53 associated with risk and prognosis in African Americans, were associated with increased odds of somatic TP53 mutation in lung tumors in Caucasians. In conclusion, common genetic variation in TP53 could modulate lung cancer pathways, as suggested by the association with lung cancer in African Americans and somatic TP53 mutation frequency in lung tumors. (Cancer Epidemiol Biomarkers Prev 2007;16(2):214–22)
Lack of endothelial cell survivin causes embryonic defects in angiogenesis, cardiogenesis, and neural tube closure
Authors: Zwerts Femke , Lupu Florea , De Vriese Astrid , Pollefeyt Saskia , Moons Lieve , Altura Rachel A. , Jiang Yuying , Maxwell Patrick H. , Hill Peter , Oh Hideyasu , Rieker Claus , Collen Désiré , Conway Simon J. , Conway Edward M. 
Published: February 2007

AbstractWe explored the physiologic role of endothelial cell apoptosis during development by generating mouse embryos lacking the inhibitor of apoptosis protein (IAP) survivin in endothelium. This was accomplished by intercrossing survivinlox/lox mice with mice expressing cre recombinase under the control of the endothelial cell specific tie1 promoter (tie1-cre mice). Lack of endothelial cell survivin resulted in embryonic lethality. Mutant embryos had prominent and diffuse hemorrhages from embryonic day 9.5 (E9.5) and died before E13.5. Heart development was strikingly abnormal. Survivin-null endocardial lineage cells could not support normal epithelial-mesenchymal transformation (EMT), resulting in hypoplastic endocardial cushions and in utero heart failure. In addition, 30% of mutant embryos had neural tube closure defects (NTDs) that were not caused by bleeding or growth retardation, but were likely due to alterations in the release of soluble factors from endothelial cells that otherwise support neural stem cell proliferation and neurulation. Thus, regulation of endothelial cell survival, and maintenance of vascular integrity by survivin are crucial for normal embryonic angiogenesis, cardiogenesis, and neurogenesis.
Inclusion of the glucocorticoid receptor in a hypothalamic pituitary adrenal axis model reveals bistability
Authors: Gupta Shakti , Aslakson Eric , Gurbaxani Brian M , Vernon Suzanne D 
Published: February 2007

Abstract

Background
The body's primary stress management system is the hypothalamic pituitary adrenal (HPA) axis. The HPA axis responds to physical and mental challenge to maintain homeostasis in part by controlling the body's cortisol level. Dysregulation of the HPA axis is implicated in numerous stress-related diseases.

Results
We developed a structured model of the HPA axis that includes the glucocorticoid receptor (GR). This model incorporates nonlinear kinetics of pituitary GR synthesis. The nonlinear effect arises from the fact that GR homodimerizes after cortisol activation and induces its own synthesis in the pituitary. This homodimerization makes possible two stable steady states (low and high) and one unstable state of cortisol production resulting in bistability of the HPA axis. In this model, low GR concentration represents the normal steady state, and high GR concentration represents a dysregulated steady state. A short stress in the normal steady state produces a small perturbation in the GR concentration that quickly returns to normal levels. Long, repeated stress produces persistent and high GR concentration that does not return to baseline forcing the HPA axis to an alternate steady state. One consequence of increased steady state GR is reduced steady state cortisol, which has been observed in some stress related disorders such as Chronic Fatigue Syndrome (CFS).

Conclusion
Inclusion of pituitary GR expression resulted in a biologically plausible model of HPA axis bistability and hypocortisolism. High GR concentration enhanced cortisol negative feedback on the hypothalamus and forced the HPA axis into an alternative, low cortisol state. This model can be used to explore mechanisms underlying disorders of the HPA axis.
Common genetic variation in IGF1, IGFBP-1, and IGFBP-3 in relation to mammographic density: a cross-sectional study
Authors: Tamimi Rulla M , Cox David G , Kraft Peter , Pollak Michael N , Haiman Christopher A , Cheng Iona , Freedman Matthew L , Hankinson Susan E , Hunter David J , Colditz Graham A 
Published: February 2007

Abstract
Introduction
Mammographic density is one of the strongest risk factors for breast cancer and is believed to represent epithelial and stromal proliferation. Because of the high heritability of breast density, and the role of the insulin-like growth factor (IGF) pathway in cellular proliferation and breast development, we examined the association between common genetic variation in this pathway and mammographic density.

Methods
We conducted a cross-sectional analysis among controls (n = 1,121) who were between the ages of 42 and 78 years at mammography, from a breast cancer case-control study nested within the Nurses' Health Study cohort. At the time of mammography, 204 women were premenopausal and 917 were postmenopausal. We genotyped 29 haplotype-tagging SNPs demonstrated to capture common genetic variation in IGF1, IGF binding protein (IGFBP)-1, and IGFBP-3.

Results
Common haplotype patterns in three of the four haplotype blocks spanning the gene encoding IGF1 were associated with mammographic density. Haplotype patterns in block 1 (p = 0.03), block 3 (p = 0.009), and block 4 (p = 0.007) were associated with mammographic density, whereas those in block 2 were not. None of the common haplotypes in the three haplotype blocks spanning the genes encoding IGFBP-1/IGFBP-3 were significantly associated with mammographic density. Two haplotype-tagging SNPs in IGF1, rs1520220 and rs2946834, showed a strong association with mammographic density. Those with the homozygous variant genotype for rs1520220 had a mean percentage mammographic density of 19.6% compared with those with the homozygous wild-type genotype, who had a mean percentage mammographic density of 27.9% (p for trend < 0.0001). Those that were homozygous variant for rs2946834 had a mean percentage mammographic density of 23.2% compared with those who were homozygous wild-type with a mean percentage mammographic density of 28.2% (p for trend = 0.0004). Permutation testing demonstrated that results as strong as these are unlikely to occur by chance (p = 0.0005).

Conclusion
Common genetic variation in IGF1 is strongly associated with percentage mammographic density.
A Disruptive Mutation in Exon 3 of the GNAS Gene with Albright Hereditary Osteodystrophy, Normocalcemic Pseudohypoparathyroidism, and Selective Long Transcript Variant Gsα-L Deficiency
Authors: Thiele Susanne , Werner Ralf , Ahrens Wiebke , Hoppe Ute , Marschke Christine , Staedt Pia , Hiort Olaf 
Published: February 2007

AbstractObjective: The GNAS gene encodes the α-subunit of stimulatory G proteins, which play a crucial role in intracellular signal transduction of peptide and neurotransmitter receptors. In addition to transcript variants that differ in their first exon due to different promoters, there are two long (Gsα-L) and two short (Gsα-S) splice variants, created by alternative splicing. Heterozygous inactivating maternally inherited mutations of GNAS lead to a phenotype in which Albright hereditary osteodystrophy is associated with pseudohypoparathyroidism type Ia.Methods and Results: The GNAS gene of a 10-yr-old girl with brachymetacarpia, mental retardation, normocalcemic pseudohypoparathyroidism, and hypothyroidism was investigated. We found a heterozygous insertion of an adenosine in exon 3 altering codon 85 and leading to a frame shift inducing a stop codon in exon 4. Molecular studies of cDNA from blood RNA demonstrated normal, biallelic expression of Gsα-S transcripts, whereas expression of Gsα-L transcripts from the maternal allele was reduced. Immunoblot analysis revealed a reduced Gsα-L protein level to about 50%, whereas the protein level of Gsα-S was unaltered. Furthermore, the Gsα protein activity in erythrocyte membranes was diminished to about 75% of normal. Both the reduced activity and the mutation were also found in the mother and the affected younger brother.Conclusion: This report demonstrates the first evidence for a pathogenic mutation in exon 3 of the GNAS gene. The mutation is associated with a phenotype of Albright hereditary osteodystrophy and pseudohypoparathyroidism type Ia due to selective deficiency of Gsα-L and a partial reduction of Gsα activity.
Use of Hematopoietic Growth Factors as Adjuvant Therapy for Anemia and Neutropenia in the Treatment of Hepatitis C
Authors: Santos Anne E Dar , Partovi Nilufar , Ford Jo-Ann E , Yoshida Eric M 
Published: February 2007

Objective: To review the hematologic adverse effects of hepatitis C virus (HCV) therapy and adjuvant treatment with epoetin alfa and granulocyte colony-stimulating factor (ie, filgrastim). Data Sources: Medical literature indexed in MEDLINE (1966–January 2007) and EMBASE (1980–January 2007) was searched, and published conference abstracts were reviewed. Study Selection and Data Extraction: Peer-reviewed articles and relevant conference abstracts regarding the use of epoetin alfa and granulocyte colony-stimulating factor were reviewed. Data Synthesis: Ribavirin induces a dose-dependent hemolytic anemia. Studies using epoetin alfa 40 000 units subcutaneously once weekly have demonstrated efficacy in maintaining hemoglobin, ribavirin dose, and quality of life scores, but clear benefit shown with sustained virologic response (SVR) is lacking. The hemoglobin threshold for initiation of epoetin alfa used in studies may not adequately reflect values used in clinical practice. Treatment-related neutropenia is caused primarily by interferon or peg interferon. Few studies have investigated the impact of granulocyte or granulocyte-macrophage colony-stimulating factor derivatives on neutropenia. Results of dose maintenance evaluation vary, and studies reporting data on SVR showed no effect from growth factor therapy. The frequency of bacterial infections was not reported. Conclusions: The role and benefit of hematopoietic growth factors in HCV therapy have not been conclusively determined to date. However, the possibility of a benefit to individual patients seen on an outpatient basis remains, and an individualized treatment approach is recommended.
Opioid Conversions in Acute Care
Authors: Patanwala Asad E , Duby Jeremiah , Waters Dustin , Erstad Brian L 
Published: February 2007

Objective: To discuss the historical basis and limitations of opioid conversion tables, review the relevant literature, and establish an evidence-based equianalgesic dose ratio (EDR) table for performing conversions in the acute care setting. Data Sources: Articles were identified through searches of MEDLINE (1966–January 2007) using the key words opioid, tolerance, conversion, dose, equianalgesic, equipotent, acute care, morphine, hydromorphone, fentanyl, methadone, and oxycodone. Additional references were located through a review of the bibliographies of articles cited and references cited in conversion tables. Study Selection and Data Extraction: All data sources identified were evaluated, and all information deemed relevant was included, with the exception of case series and case reports when higher level evidence was available. Data Synthesis: Opioid conversion tables are published in major textbooks, medical references, national guidelines, and review articles. Some conversion tables do not accurately reflect the dose ratios for which evidence is available. There is marginal evidence-based clinical data to support the dose ratios cited in these tables, particularly in the acute care setting where the clinical status of patients often changes rapidly. The barriers when performing route and opioid-to-opioid conversions in the acute care setting are formidable, but EDRs are provided, based on the best available evidence. Conclusions: In the acute care setting, calculation of dose ratios for opioids, based solely on opioid conversion tables, is an oversimplification of pain management, with a potential for adverse consequences. The calculation of EDRs is one step in an interdisciplinary process that must take into account patient- and institution-specific factors.
The impact of mood induction on the accessibility of positive and negative future events in a group of dysphoric adolescent in‐patients
Authors: de Jong‐Meyer Renate , Kuczmera Arkadius , Tripp Jürgen 
Published: February 2007

Objective. This study aimed at experimentally affecting the fluency with which positive and negative future events are generated by depressive adolescents.Method. Adolescent in‐patients with elevated depression were randomized into a positive or negative mood induction condition (N=24 in each group) and then presented with the Future Thinking Task asking participants to generate as many future events of a specified valence as possible.Results. The inductions resulted in significant mood differences between groups. The assumed interaction between mood condition and reported positive and negative future events was confirmed. Particularly, the generation of negative future event representations differed between the mood induction groups.Conclusions. Dysphoric adolescents given a negative mood induction differ from those given a positive mood induction in their ability to think of future positive and negative events that they might experience.