There is growing evidence that common variants of the transforming growth factor-beta (TGF-beta) signaling pathway may modify breast cancer risk. In vitro studies have shown that some variants increase TGF-beta signaling, whereas others have an opposite effect. We tested the hypothesis that a combined genetic assessment of two well-characterized variants may predict breast cancer risk. Consecutive patients (n = 660) with breast cancer from the Memorial Sloan-Kettering Cancer Center (New York, NY) and healthy females (n = 880) from New York City were genotyped for the hypomorphic TGFBR1*6A allele and for the TGFB1 T29C variant that results in increased TGF-beta circulating levels. Cases and controls were of similar ethnicity and geographic location. Thirty percent of cases were identified as high or low TGF-beta signalers based on TGFB1 and TGFBR1 genotypes. There was a significantly higher proportion of high signalers (TGFBR1/TGFBR1 and TGFB1*CC) among controls (21.6%) than cases (15.7%; P = 0.003). The odds ratio [OR; 95% confidence interval (95% CI)] for individuals with the lowest expected TGF-beta signaling level (TGFB1*TT or TGFB1*TC and TGFBR1*6A) was 1.69 (1.08-2.66) when compared with individuals with the highest expected TGF-signaling levels. Breast cancer risk incurred by low signalers was most pronounced among women after age 50 years (OR, 2.05; 95% CI, 1.01-4.16). TGFBR1*6A was associated with a significantly increased risk for breast cancer (OR, 1.46; 95% CI, 1.04-2.06), but the TGFB1*CC genotype was not associated with any appreciable risk (OR, 0.89; 95% CI, 0.63-1.21). TGFBR1*6A effect was most pronounced among women diagnosed after age 50 years (OR, 2.20; 95% CI, 1.25-3.87). This is the first study assessing the TGF-beta signaling pathway through two common and functionally relevant TGFBR1 and TGFB1 variants. This approach may predict breast cancer risk in a large subset of the population.

Using the filter paper disk diffusion assay technique as a tool in our antibiotic screening program, occasional samples have been encountered that were without inhibitory activity but induced a marked stimulation of the test organism, Bacillus subtilis, ATCC 6633. This effect was manifested as a zone of heavy growth in the region of the plate surrounding the disk saturated with the sample under test and was sharply demarcated from a less dense background. Low power microscopic examination of the area revealed larger surface colonies in the stimulated area. Within this stimulated zone, occasional subsurface colonies could be seen that were comparable in size with the smaller colonies in the area outside the stimulated zone, suggesting that stimulation of growth occurred only under conditions of strict aerobiosis. When an extract of Streptomyces sp mycelium became available that consistently produced the effect, an attempt was made to isolate the stimulatory factor. It was found that an acid extract of the ash of the sample contained the active principle. Tests with various inorganic ions revealed that manganese salts SUMMARY Manganese has been shown to stimulate sporulation of several species of the genus Bacillus. Sporulation is specifically dependent upon the presence of manganese at a concentration greater than that required for full vegetative growth of BaciUus subtilis, ATCC 6633, which was studied further as a representative of the genus.

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CEUS increases the conspicuity and provides better characterization of hypervascular HCC that are either not seen or poorly seen on B-mode US, and CEUS provides real-time guidance of RFA with good short-term treatment responses.