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  • 2000-2004  (6)
  • 1995-1999  (3)
  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Clinical & experimental allergy 32 (2002), S. 0 
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Previously, an association has been reported between an increased risk of asthma and a polymorphism in the Clara cell secretory protein (CC16) gene [namely, an adenine to guanine substitution in the CC16 gene at position 38 (A38G) downstream from the transcription initiation site within the noncoding region of exon 1]. Homozygous individuals for the polymorphic sequence (AA genotype) were reported to have a significant (6.9 fold) increased risk of developing asthma. This finding has not been confirmed independently.Objective To validate the association of CC16 A38G polymorphism to asthma in a separate well-characterized population through a case–control study.Methods We conducted an association study using a sample of 217 unrelated Northern European Caucasians. Individuals were clinically characterized by a validated respiratory questionnaire, spirometry and bronchial reactivity measurement, and genotyped for the A38G polymorphism using PCR and restriction digestion. Association analysis was performed using the nonparametric Chi-squared tests.Results In the unselected population, 43.3% participants were homozygous for the CC16*G allele and 45.4% were heterozygous (AG). We observed no significant difference in the distribution of positive bronchial reactivity to methacholine (at FEV1 PC20 of ≤ 8 mg/mL) across the three genotypes. Homozygous individuals for the CC16*A allele did not demonstrate an increased risk of asthma when compared to heterozygous or GG homozygotes. In addition, no significant difference was observed in the distribution of the CC16*A or *G alleles in the asthmatics vs. non-asthmatics.Conclusion CC16 polymorphism A38G does not influence the predisposition to asthma in this sample.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford BSL : Blackwell Science Ltd
    Clinical & experimental allergy 29 (1999), S. 0 
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Both in humans and in experimental animals, much of the airway hyperresponsiveness that accompanies viral infections is the result of increased reflex bronchoconstriction. The M3 muscarinic receptors on the airway smooth muscle function normally during viral infections so that the direct effects of acetylcholine on the smooth muscle are not altered. In contrast, the M2 muscarinic receptors on the vagal nerve endings, which normally inhibit acetycholine release, are markedly dysfunctional during viral infections. This leads to substantial increases in acetylcholine release and potentiated reflex bronchoconstriction. Multiple mechanisms account for virus-induced M2 receptor dysfunction. Viral neuraminidase may deglycosylate the M2 receptor, decreasing acetylcholine affinity. Furthermore, both viruses and interferon-γ decrease M2 receptor gene expression. Finally, in atopic hosts, viral infection causes M2 receptor dysfunction by activating eosinophils, causing them to release major basic protein which binds to the M2 receptor, functioning as an endogenous antagonist.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 143 (2000), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: A patient with both neurofibromatosis type 1 (NF-1) and McCune–Albright syndrome is described. NF-1 and McCune–Albright are separate entities and this is the first report of a patient with clear evidence of both conditions.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Clinical and experimental dermatology 25 (2000), S. 0 
    ISSN: 1365-2230
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We present the case of a 53-year-old Caucasian woman with seven basal cell carcinomas and one malignant melanoma in situ along her back overlying her spine, which was irradiated in 1968 for ankylosing spondylitis. These lesions developed between 1997 and 1999. She has no other known risk factors for cutaneous malignancy, in particular no history of excessive sun exposure. She has skin type 2. Molecular studies of glutathione S-transferase and cytochrome P450 status showed her genotype not to constitute an overall increased inherited susceptibility. We therefore postulate that all her skin cancers have arisen as a consequence of her radiotherapy. To our knowledge this is the first case of multiple basal cell carcinoma in addition to a malignant melanoma following radiotherapy for benign disease.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Susceptibility and outcome in complex disorders such as asthma and cancer appear to be determined, at least in part, by genetic polymorphism. However, while our ability to identify new allelic variants and study them in case and control populations has greatly improved, considerable difficulties remain in elucidating how many genes determine particular clinical phenotypes. This is because most studies have concentrated on study of single genes in relatively small study groups. The important issues of gene–gene interactions (epistasis) and high-risk subgroups have not yet been adequately addressed. We now describe a general approach, using patients with head and neck cancers as an example. Our purpose is to demonstrate candidate gene selection, statistical approaches, and identification of patient subgroups.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: A common feature of environmental irritants is their ability to cause local inflammation which could alter airway function. The principal targets of such injury are the epithelial cells lining the airway passages and the lower respiratory gas-exchange areas. While host atopy is a recognized risk factor for airway inflammation, atopy alone cannot cause asthma. We hypothesize that susceptibility to persistent airway inflammation in atopic individuals is characterized by an inherited deficiency in the effectiveness of detoxification of inhaled irritants and products of oxidative stress such as reactive oxygen species (ROS). Our case-control studies show that polymorphisms at the glutathione S-transferase, GSTP1, locus on chromosome 11q13 may account for variation in host response to oxidative stress, a key component of airway inflammation. Frequency of the GSTP1 Val/Val genotype is reduced in atopic subjects compared with nonatopic subjects. Trend analysis also shows a significant decrease of GSTP1 Val/Val (with parallel increase of GSTP1 Ile/Ile) genotype frequency with increasing severity of airflow obstruction/bronchial hyperresponsiveness. The implication of specific polymorphisms at the GSTP1 locus in airway inflammation is entirely novel: however, GST are recognized as a supergene family of enzymes critical in 1) cell protection from the toxic products of ROS-mediated reactions, 2) modulation of eicosanoid synthesis.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-1459
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Pediatric radiology 26 (1996), S. 678-679 
    ISSN: 1432-1998
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The case of a 20-week fetus is reported with almost completely deficient ossification of the vertebral bodies and absent ossification of several long bones. This could be a unique skeletal dysplasia or the most severe end of the atelosteogenesis spectrum.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    European archives of oto-rhino-laryngology and head & neck 254 (1997), S. S147 
    ISSN: 1434-4726
    Keywords: Squamous cell carcinoma ; Larynx ; Genetic predisposition ; Glutathione S-transferase ; GSTM1, GSTM3 and GSTT1 genotypes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract While cigarette smoking and alcohol consumption have been linked to laryngeal squamous cell carcinoma (SCC), the role of genetic factors in determining individual susceptibility is unknown. We describe the role of allelism at the glutathione S-transferase GSTM1, GSTM3, GSTT1 and cytochrome P450 CYPIA1, CYP2E1, CYP2D6 loci in determining individual susceptibility to laryngeal SCC. Enzyme genotypes were determined using polymerase chain reaction and restriction enzyme digestion of leukocyte DNA collected from 269 patients with T1–T4 laryngeal carcinomas and 216 controls. While the frequencies of the heterozygote GSTM1 A/B genotype and the homozygote GSTM3 B/B genotype were statistically significantly lower in the patients with tumors than in controls, the frequency of the GSTT1 null genotype was higher in the patients than in controls. The data suggest that allelism at GST loci mediates susceptibility to SCC of the larynx. GSTM1 A/B and GSTM3 B/B appear to be associated with reduced risk, while GSTT1 null may confer increased risk. These findings are compatible with the view that genetic predisposition is important in determining risk for this cancer.
    Type of Medium: Electronic Resource
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