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  • 1
    Keywords: UNITED-STATES ; BEHAVIOR ; SMOKERS ; CLUSTER ; GENOME-WIDE ASSOCIATION ; GENETIC-VARIATION ; NICOTINE DEPENDENCE ; INTERPLAY ; CHRNA5-CHRNA3-CHRNB4 ; QUANTITY
    Abstract: Background: Recent meta-analyses show strong evidence of associations among genetic variants in CHRNA5 on chromosome 15q25, smoking quantity, and lung cancer. This meta-analysis tests whether the CHRNA5 variant rs16969968 predicts age of smoking cessation and age of lung cancer diagnosis. Methods: Meta-analyses examined associations between rs16969968, age of quitting smoking, and age of lung cancer diagnosis in 24 studies of European ancestry (n = 29 072). In each dataset, we used Cox regression models to evaluate the association between rs16969968 and the two primary phenotypes (age of smoking cessation among ever smokers and age of lung cancer diagnosis among lung cancer case patients) and the secondary phenotype of smoking duration. Heterogeneity across studies was assessed with the Cochran Q test. All statistical tests were two-sided. Results: The rs16969968 allele (A) was associated with a lower likelihood of smoking cessation (hazard ratio [HR] = 0.95, 95% confidence interval [CI] = 0.91 to 0.98, P =.0042), and the AA genotype was associated with a four-year delay in median age of quitting compared with the GG genotype. Among smokers with lung cancer diagnoses, the rs16969968 genotype (AA) was associated with a four-year earlier median age of diagnosis compared with the low-risk genotype (GG) (HR = 1.08, 95% CI = 1.04 to 1.12, P = 1.1*10(-5)). Conclusion: These data support the clinical significance of the CHRNA5 variant rs16969968. It predicts delayed smoking cessation and an earlier age of lung cancer diagnosis in this meta-analysis. Given the existing evidence that this CHRNA5 variant predicts favorable response to cessation pharmacotherapy, these findings underscore the potential clinical and public health importance of rs16969968 in CHRNA5 in relation to smoking cessation success and lung cancer risk.d: Recent meta-analyses show strong evidence of associations among genetic variants in CHRNA5 on chromosome 15q25, smoking quantity, and lung cancer. This meta-analysis tests whether the CHRNA5 variant rs16969968 predicts age of smoking cessation and age of lung cancer diagnosis.
    Type of Publication: Journal article published
    PubMed ID: 25873736
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  • 2
    Abstract: BACKGROUND: Recent meta-analyses show that individuals with high risk variants in CHRNA5 on chromosome 15q25 are likely to develop lung cancer earlier than those with low-risk genotypes. The same high-risk genetic variants also predict nicotine dependence and delayed smoking cessation. It is unclear whether smoking cessation confers the same benefits in terms of lung cancer risk reduction for those who possess CHRNA5 risk variants versus those who do not. METHODS: Meta-analyses examined the association between smoking cessation and lung cancer risk in 15 studies of individuals with European ancestry who possessed varying rs16969968 genotypes (N=12,690 ever smokers, including 6988 cases of lung cancer and 5702 controls) in the International Lung Cancer Consortium. RESULTS: Smoking cessation (former vs. current smokers) was associated with a lower likelihood of lung cancer (OR=0.48, 95%CI=0.30-0.75, p=0.0015). Among lung cancer patients, smoking cessation was associated with a 7-year delay in median age of lung cancer diagnosis (HR=0.68, 95%CI=0.61-0.77, p=4.9 *10-10). The CHRNA5 rs16969968 risk genotype (AA) was associated with increased risk and earlier diagnosis for lung cancer, but the beneficial effects of smoking cessation were very similar in those with and without the risk genotype. CONCLUSION: We demonstrate that quitting smoking is highly beneficial in reducing lung cancer risks for smokers regardless of their CHRNA5 rs16969968 genetic risk status. Smokers with high-risk CHRNA5 genotypes, on average, can largely eliminate their elevated genetic risk for lung cancer by quitting smoking- cutting their risk of lung cancer in half and delaying its onset by 7years for those who develop it. These results: 1) underscore the potential value of smoking cessation for all smokers, 2) suggest that CHRNA5 rs16969968 genotype affects lung cancer diagnosis through its effects on smoking, and 3) have potential value for framing preventive interventions for those who smoke.
    Type of Publication: Journal article published
    PubMed ID: 27543155
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  • 3
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Children and Youth Services Review 4 (1982), S. 325-350 
    ISSN: 0190-7409
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine , Education , Psychology
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 0304-4165
    Keywords: Asialoglycoprotein receptor ; Drug targeting ; Lipid vesicle ; Liver disease ; Pharmacokinetics
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Medicine , Physics
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0983
    Keywords: DNA damage ; Protein induction ; Neurospora
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Two-dimensional polyacrylamide gel electrophoresis has been used to analyze proteins from wild type and mutagen sensitive mutants of Neurospora crassa under constitutive conditions and after treatment with mutagens and other stress inducing agents. Several proteins have been detected that are either induced or show changes in electrophoretic mobility in response to UV irradiation, 4-NQO, X-ray, paraquat and heat shock. Ten proteins were found to respond to more than one of the stress inducing agents, demonstrating a complex pattern of polypeptide inductions. The significance of these findings and the possible effects of some of these proteins on the DNA repair process and stress management are discussed.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Aesthetic plastic surgery 11 (1987), S. 199-201 
    ISSN: 1432-5241
    Keywords: Facial mimics ; Rhytidectomy ; Coronal browlift
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The classic rhytidectomy leaves the upper third of the face without improvement. Yet the eye-eyebrow region is the most influential in determining facial expressions. There is only a narrow range of positions of the eyebrows in which they are perceived as attractive. The influence of the coronal browlift on facial mimics is discussed as it seems to be a way to predictably reposition the eyebrows and improve crow's feet and forehead, and glabellar wrinkles at the same time. The results of 56 patients surveyed 1–3 years postoperatively are presented.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Annals of combinatorics 3 (1999), S. 159-170 
    ISSN: 0219-3094
    Keywords: 33C80 ; Jack polynomials ; symmetric functions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Abstract We show how a number of fundamental properties of the symmetric and anti-symmetric Jack polynomials can be derived from knowledge of the corresponding properties of the nonsymmetric Jack polynomials. These properties include orthogonality relations, normalization formulas, a specialization formula and the evaluation of a proportionality constant relating the anti-symmetric Jack polynomials to a product of differences multiplied by the symmetric Jack polynomials with a shifted parameter.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Chromosoma 22 (1967), S. 358-377 
    ISSN: 1432-0886
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Primordial oocytes (oocytes in primordial follicles) from human ovaries aged 51/2 months post conception to 11 3/4 years post partum were examined in: (a) squash preparations of fresh and fixed tissue; (b) histological preparations; and (c) thin sections by electron microscopy, in order to study the structure of the chromosomes. — The light microscope shows that the chromosome consists of a thread bearing numerous fine lateral appendages. Cytochemical tests indicate that the thread contains DNA, and is surrounded by material containing RNA and protein. — The electron microscope shows that there are three main structural components in the chromosome: (i) an axis or “core” containing at least two longitudinal strands about 200 Å thick; (ii) a surrounding sheath composed of coiled fibrils which form symmetrically arranged columns and loops, and (iii) clusters of large granules which are associated with the outer parts of the sheath. Small nucleoli and other granular bodies are also present. — These observations indicate the presence of lampbrush chromosomes in the human oocyte. The significance of this type of chromosome in mammals is discussed in relation to the differential radiosensitivity of the oocytes, and to the form of chromosomes at the dictyate stage in rodents.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0983
    Keywords: Histidine sensitivity ; DNA damage ; Protein induction ; Neurospora
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Previous work in other laboratories has shown that several mutagen sensitive mutants of Neurospora crassa are extremely sensitive to low levels of histidine in the culture medium. We have shown that wild type Neurospora accumulates nicks or breaks in the DNA in the presence of histidine. The number of nicks accumulating in histidine sensitive mutants is found to increase in relation to their sensitivity to histidine. Although these nicks can be repaired by both wild type and histidine sensitive mutants when histidine is removed from the medium, a steady state number of nicks exists as long as histidine is present. We suggest that the presence of these nicks or breaks induces an increase in recombination in these possibly recombination defective mutants and that this is the source of the high level of histidine sensitivity. We speculate on the mechanisms by which histidine induces this DNA damage. This report also shows that several polypeptides are induced by the wild type organism in the presence of histidine. Some of these polypeptides are also induced during other stress situations, such as heat shock and DNA damage due to ultraviolet irradiation. Two of the histidine induced proteins cannot be induced by any of the histidine sensitive mutants.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0983
    Keywords: DNA repair ; Pyrimidine dimers ; Epistasis groups ; Neurospora crassa
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary DNA repair mutants in eucaryotes are normally assigned to three epistasis groups. Each epistasis group represents a “pathway” for DNA repair. The pathways are commonly designated (1) nucleotide excision repair, (2) recombination repair and (3) mutagenic repair. An excision repair epistasis group has been established in Neurospora and the mutants assigned to this group should be limited in their ability to excise pyrimidine dimers and other bulky lesions from DNA. Using a pyrimidine dimer-specific assay, we have found that all Neurospora crassa mutants assigned to the excision repair epistasis group are capable of removing pyrimidine dimers from the DNA at a rate similar to the wild-type organism.
    Type of Medium: Electronic Resource
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