GATA-binding protein 3 (GATA3) is a transcription factor that is crucial to mammary gland morphogenesis and differentiation of progenitor cells, and has been suggested to have a tumor suppressor ...function. The rs570613 single nucleotide polymorphism (SNP) in intron 4 of GATA3 was previously found to be associated with a reduction in breast cancer risk in the Cancer Genetic Markers of Susceptibility project and in pooled analysis of two case-control studies from Norway and Poland (P trend = 0.004), with some evidence for a stronger association with estrogen receptor (ER) negative tumours Garcia-Closas M et al. (2007) Cancer Epidemiol Biomarkers Prev 16:2269-2275. We genotyped GATA3 rs570613 in 6,388 cases and 4,995 controls from the Breast Cancer Association Consortium (BCAC) and 5,617 BRCA1 and BRCA2 carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). We found no association between this SNP and breast cancer risk in BCAC cases overall (ORper₋allele = 1.00, 95% CI 0.94-1.05), in ER negative BCAC cases (ORper₋allele = 1.02, 95% CI 0.91-1.13), in BRCA1 mutation carriers RRper₋allele = 0.99, 95% CI 0.90-1.09) or BRCA2 mutation carriers (RRper₋allele = 0.93, 95% CI 0.80-1.07). We conclude that there is no evidence that either GATA3 rs570613, or any variant in strong linkage disequilibrium with it, is associated with breast cancer risk in women.
Seventy-two patients with seborrheic dermatitis were treated once daily with 2% ketoconazole cream (n = 36) or 1% hydrocortisone cream (n = 36) on a double-blind basis for 4 weeks. For the global ...evaluation, no significant difference could be seen between the two groups. The clinical response was 80.5% in the ketoconazole group and 94.4% in the hydrocortisone group. For the different symptoms combined (scaling, redness, itching, and papules), no significant difference was seen between the two groups when the total scores at week 2 and at week 4 were compared with the initial scores. The incidence of side effects in both groups was comparably low.
Dynamic traffic assignment (DTA) systems integrate complex transportation demand and network supply simulation models to estimate current traffic conditions, predict future network performance and ...generate consistent, anticipatory route guidance. Before they are applied, DTA system parameters and inputs must be calibrated to accurately reflect travel behavior and traffic dynamics. This paper presents a systematic approach that unifies the off-line and on-line calibration of DTA systems through a common framework. Off-line calibration simultaneously estimates demand and supply model parameters. The on-line calibration jointly updates in real-time the demand and supply parameter values estimated during the off-line step to better reflect prevailing conditions. The methods are general and can utilize any available traffic surveillance information (including emerging data sources, such as Automated Vehicle Identification systems or probe vehicles). The two components complement each other so that the calibration of the DTA system parameters efficiently utilizes both historical as well as real-time information. The calibration approaches are demonstrated with DynaMIT (Dynamic network assignment for the Management of Information to Travelers), using time-varying count, speed and density data obtained from standard loop detectors.
Derivative spectrophotometric and high performance liquid chromatographic methods, for the determination of the centrally acting cough supressant clobutinol hydrochloride in syrups and drops have ...been developed. Spectrophotometrically clobutinol was determined by the measurement of its first (
1
D) and second (
2
D) derivative amplitudes at 277 and 275 nm. The aqueous acidic and alcoholic solutions obeyed Beer's law in the concentration range of 31.4-219.5 and 34.9-157.0 µg/ml measurements respectively. A liquid chromatographic assay has been also developed for the determination of clobutinol in the presence of other pharmaceutical compounds in the same pharmaceutical formulations. A reversed phase column Alltech (Lichrosorb 5 µm 250 × 4.6 mm id) was used with a mobile phase containing ammonium acetate buffer 0.05 M, methanol and CH
3
CN, 22:60:18 adjusted to pH 3.34 with acetic acid at a flow rate of 1 ml min
−1
. The retention behaviour of clobutinol as function of both pH and mobile phase composition was investigated. Quantitation was achieved with UV detection at 267 nm based on peak height. Beer's law was obeyed in a concentration range of 34.7-243.0 µg/ml. For the described methods the regression line equations were derived with a correlation coefficient better than 0.9973. The proposed procedures were successfully applied to the determination of clobutinol hydrochloride in commercial pharmaceutical formulations and in placebo syrup prepared in the laboratory with good accuracy and precision. No significant differences were found between the results obtained both by the HPLC and derivative procedures.
Surgical Diseases of Anus and Anal Canal Nicolaidis, C; Kalliterakis, E; Kralios, N ...
Proceedings of the Royal Society of Medicine,
03/1969, Letnik:
62, Številka:
3
Journal Article
Carcinoma of the Colon Nicolaidis, C; Kalliterakis, E; Antoniou, C ...
Proceedings of the Royal Society of Medicine,
03/1969, Letnik:
62, Številka:
3
Journal Article
TwoATM variants and breast cancer risk Thompson, Deborah; Antoniou, Antonis C.; Jenkins, Mark ...
Human mutation,
06/2005, Letnik:
25, Številka:
6
Journal Article
In computing the probability that a woman is a BRCA1 or BRCA2 carrier for genetic counselling purposes, it is important to allow for the fact that other breast cancer susceptibility genes may exist. ...We used data from both a population based series of breast cancer cases and high risk families in the UK, with information on BRCA1 and BRCA2 mutation status, to investigate the genetic models that can best explain familial breast cancer outside BRCA1 and BRCA2 families. We also evaluated the evidence for risk modifiers in BRCA1 and BRCA2 carriers. We estimated the simultaneous effects of BRCA1, BRCA2, a third hypothetical gene `BRCA3', and a polygenic effect using segregation analysis. The hypergeometric polygenic model was used to approximate polygenic inheritance and the effect of risk modifiers. BRCA1 and BRCA2 could not explain all the observed familial clustering. The best fitting model for the residual familial breast cancer was the polygenic, although a model with a single recessive allele produced a similar fit. There was also significant evidence for a modifying effect of other genes on the risks of breast cancer in BRCA1 and BRCA2 mutation carriers. Under this model, the frequency of BRCA1 was estimated to be 0.051% (95% CI: 0.021 - 0.125%) and of BRCA2 0.068% (95% CI: 0.033 - 0.141%). The breast cancer risk by age 70 years, based on the average incidence over all modifiers was estimated to be 35.3% for BRCA1 and 50.3% for BRCA2. The corresponding ovarian cancer risks were 25.9% for BRCA1 and 9.1% for BRCA2. The findings suggest that several common, low penetrance genes with multiplicative effects on risk may account for the residual non-BRCA1/2 familial aggregation of breast cancer. The modifying effect may explain the previously reported differences between population based estimates for BRCA1/2 penetrance and estimates based on high-risk families.
L-Phenylalanine is a promising agent for the treatment of vitiligo when taken orally and followed with ultraviolet light (UVA) irradiation. Of 13 children so treated, 3 experienced repigmentation of ...all vitiliginous areas, 6 showed 50% to 90% improvement, and 4 failed to respond. None of the children experienced side effects during the treatment.
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