With the goal of identifying genes that have an expression pattern that can facilitate the diagnosis of primary breast cancers (BCs) as well as the discovery of novel drug leads for BC treatment, we ...used cDNA hybridization arrays to analyze the gene expression profiles (GEPs) of nine weakly invasive and four highly invasive BC cell lines. Differences in gene expression between weakly and highly invasive BC cells were identified that enabled the definition of consensus GEPs for each invasive phenotype. To determine whether the consensus GEPs, comprising 24 genes, could be used to predict the aggressiveness of previously uncharacterized cells, gene expression levels and comparative invasive and migratory characteristics of nine additional human mammary epithelial cell strains/lines were determined. The results demonstrated that the GEP of a cell line is predictive of its invasive and migratory behavior, as manifest by the morphology of its colonies when cultured on a matrix of basement membrane constituents (i.e., Matrigel). We found that the expression of keratin 19 was consistently elevated in the less aggressive BC cell lines and that vimentin and fos-related antigen-1 (FRA-1) were consistently overexpressed in the more highly aggressive BC cells. Moreover, even without these three genes, the GEP of a cell line still accurately predicted the aggressiveness of the BC cell, indicating that the expression pattern of multiple genes may be used as BC prognosticators because single markers often fail to be predictive in clinical specimens.
As part of the MILAGRO field campaign, the DOE G-1 aircraft was used to make measurements over and downwind of Mexico City with the objective of determining growth characteristics of aerosols from a ...megacity urban source. This study focuses on number concentration and size distributions. It is found that a 5-fold increase in aerosol volume is accompanied by about a 5-fold increase in accumulation mode number concentration. There is growth in aerosol volume because there are more accumulation mode particles, not because of an increase in the average size of accumulation particles. Condensation and volume growth laws were examined to see whether either is consistent with observations. Condensation calculations show that the growth of Aitken mode particles into the accumulation mode size range gives the required increase in number concentration. There are minimal changes in the accumulation mode size distribution with age, consistent with observations. Volume-growth in contrast yields a population of large particles, distinctly different from what is observed. Detailed model calculations are required to translate our observations into specific information on the volatility and properties of secondary organic aerosol.
Purpose
: Between June 1988 and June 1994, 38 hemangioblastomas were treated with stereotactic radiosurgery (SR) at three SR centers to evaluate the efficacy and potential toxicity of this ...therapeutic modality as an adjuvant or alternative treatment to surgical resection.
Methods and Materials
: SR was performed using either a 201-cobalt source unit or a dedicated SR linear accelerator. Of the 18 primary tumors treated, 16 had no prior history of surgical resection and were treated definitively with SR and two primary lesions were subtotally resected and subsequently treated with SR. Twenty lesions were treated with SR after prior surgical failure (17 tumors) or failure after prior surgery and conventional radiotherapy (three tumors). Eight patients were treated with SR for multifocal disease (total, 24 known tumors). SR tumor volumes measured 0.05 to 12 cc (median: 0.97 cc). Minimum tumor doses ranged from 12 to 20 Gy (median: 15.5 Gy).
Results
: Median follow-up from the time of SR was 24.5 months (range: 6–77 months). The 2-year actuarial overall survival was 88 ± 15% (95% confidence interval). Two-year actuarial freedom from progression was 86 ± 12% (95% confidence interval). The median tumor volume of the lesions that failed to be controlled by SR was 7.85 cc (range: 3.20–10.53 cc) compared to 0.67 cc (range: 0.05–12 cc) for controlled lesions (
p = 0.0023). The lesions that failed to be controlled by SR received a median minimum tumor dose of 14 Gy (range: 13–17 Gy) compared to 16 Gy (range: 12–20 Gy) for controlled lesions (
p = 0.0239). Seventy-eight percent of the surviving patients remained neurologically stable or clinically improved. There were no significant permanent complications directly attributable to SR.
Conclusions
: This report documents the largest experience in the literature of the use of SR in the treatment of hemangioblastoma. We conclude that SR: (a) controls the majority of primary and recurrent hemangioblastomas; (b) offers the ability to treat multiple lesions in a single treatment session, which is particularly important for patients with Von Hippel-Lindau Syndrome; and that (c) better control rates are associated with higher doses and smaller tumor volumes.
The plant-pathogenic fungus Mycosphaerella graminicola (asexual stage: Septoria tritici) causes septoria tritici blotch, a disease that greatly reduces the yield and quality of wheat. This disease is ...economically important in most wheat-growing areas worldwide and threatens global food production. Control of the disease has been hampered by a limited understanding of the genetic and biochemical bases of pathogenicity, including mechanisms of infection and of resistance in the host. Unlike most other plant pathogens, M. graminicola has a long latent period during which it evades host defenses. Although this type of stealth pathogenicity occurs commonly in Mycosphaerella and other Dothideomycetes, the largest class of plant-pathogenic fungi, its genetic basis is not known. To address this problem, the genome of M. graminicola was sequenced completely. The finished genome contains 21 chromosomes, eight of which could be lost with no visible effect on the fungus and thus are dispensable. This eight-chromosome dispensome is dynamic in field and progeny isolates, is different from the core genome in gene and repeat content, and appears to have originated by ancient horizontal transfer from an unknown donor. Synteny plots of the M. graminicola chromosomes versus those of the only other sequenced Dothideomycete, Stagonospora nodorum, revealed conservation of gene content but not order or orientation, suggesting a high rate of intra-chromosomal rearrangement in one or both species. This observed "mesosynteny" is very different from synteny seen between other organisms. A surprising feature of the M. graminicola genome compared to other sequenced plant pathogens was that it contained very few genes for enzymes that break down plant cell walls, which was more similar to endophytes than to pathogens. The stealth pathogenesis of M. graminicola probably involves degradation of proteins rather than carbohydrates to evade host defenses during the biotrophic stage of infection and may have evolved from endophytic ancestors.
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The activity of fusion genes containing fragments of the COL1A1 promoter was measured in tissues from 6- to 8-day-old transgenic mice. ColCAT3.6 contains approximately 3.6 kb (-3521 to 115 bp) of the ...rat COL1A1 gene, the chloramphenicol acetyltransferase (CAT) reporter gene, and the SV40 splice and polyadenylation sequences. ColCAT2.3 and ColCAT1.7 are deletion constructs that contain 2296 and 1667 bp of COL1A1 upstream from the RNA start site, respectively. For each transgene, up to six lines of mice were characterized. Both ColCAT3.6 and ColCAT2.3 had similar activity in bone and tooth; ColCAT1.7 was inactive. In transgenic calvariae, levels of transgene mRNA paralleled levels of CAT activity. In tendon, the activity of ColCAT2.3 was 3- to 4-fold lower than that of ColCAT3.6, and the activity ColCAT1.7 was 16-fold lower than that of ColCAT2.3. There was little activity of the ColCAT constructs in liver and brain. These data show that DNA sequences between -2.3 and -1.7 kb are required for COL1A1 promoter expression in bone and tooth; sequences that control expression in tendon are distributed between -3.5 and -1.7 kb of the promoter, with sequences downstream of -1.7 kb still capable of directing expression to this tissue. The cis elements that govern basal expression of COL1A1 in transgenic calvariae appear to be different from those required for optimal expression of the COL1A1 promoter in stably transfected osteoblastic cells.
To evaluate stable rough mutants derived from Brucella melitensis 16M and B suis 2579 (biovar 4) as vaccines against homologous and heterologous Brucella spp in the BALB/c mouse model. DESIGN, ...ANIMALS, AND PROCEDURE: Rough mutants VTRM1 and VTRS1 were obtained from B melitensis 16M and B suis 2579, respectively, by allelic exchange of rfbU gene encoding mannosyltransferase with a Tn5-disrupted rfbU gene. Mice were vaccinated with VTRM1 or VTRS1 and challenge exposed 8 weeks later.
VTRM1 and VTRS1 replicated extensively in the spleen during the first 3 weeks of infection, then decreased rapidly. Antibodies specific for the O polysaccharide were not detected in sera of mice inoculated with either rough strain. Vaccination with VTRM1 or VTRS1 induced protection against virulent strains of B abortus (2308), B melitensis (16M), B suis biovar 1 (750), and B suis biovar 4 (2579). VTRM1 also protected against B ovis (PA) and against 4 field isolates of B abortus from bison or elk. VTRS1 conferred protection against 4 field isolates of B suis biovar 4 from reindeer. Vaccines prepared from live VTRM1 or VTRS1 provided significantly greater protection than that afforded by vaccines of killed cells in QS-21 adjuvant. Vaccination with VTRM1 containing VTRS1 gave minimal protection against the antigenically unrelated Listeria monocytogenes, thus demonstrating the immunologic specificity of protection against Brucella spp.
Results encourage evaluation, in primary host species, of VTRM1 and VTRS1, along with RB51, as alternative vaccines to strain 19, Rev 1, or other smooth phase vaccines.
Interleukin‐1 (IL‐1) inhibits collagen synthesis in osteoblastic cell lines and primary osteoblast‐like cells. However, promoter elements regulating type I collagen A1 (COLIA1) expression in vivo and ...in organ culture may differ from those regulating expression in cell culture. We have examined the effects of IL‐1 on reporter gene activity in neonatal transgenic mouse calvariae bearing COLIA1 promoter‐chloramphenicol acetyltransferase (ColCAT) fusion genes. The parent construct, ColCAT 3.6, contains 3.5 kb of 5′ flanking sequence and 115 bp of 5′ untranslated region fused to the CAT reporter. In 48‐h calvarial organ cultures, IL‐1 repressed ColCAT 3.6 promoter activity and collagen synthesis in a dose‐related manner, with a maximal inhibition of 40–65%. This repression was retained in 5′ deletion constructs truncated to −1719 bp. The inhibition of transgene mRNA was blocked by cycloheximide, indicating a requirement for new protein synthesis. Pretreatment with indomethacin diminished the inhibitory effect of IL‐1 on CAT activity and collagen synthesis, suggesting partial mediation by prostaglandins. Local in vivo injection of IL‐1 (500 ng) decreased calvarial transgene mRNA after 8 h, an effect that was partially blocked by indomethacin. ColCAT transgenic mice represent a useful model for in vitro and in vivo assessment of COLIA1 promoter regulation by cytokines and other factors.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
A search for the narrow structure, X(5568), reported by the D0 Collaboration in the decay sequence $X → B_s^0 π^±, B_s^0 → J/ψϕ$, is presented. The analysis is based on a data sample recorded with ...the ATLAS detector at the LHC corresponding to 4.9 fb$^{-1}$ of pp collisions at 7 TeV and 19.5 fb$^{-1}$ at 8 TeV. No significant signal was found. Upper limits on the number of signal events, with properties corresponding to those reported by D0, and on the X production rate relative to $B_s^0$ mesons, $ρ_X$, were determined at 95% confidence level. The results are $N(X) < $ 382 and $ρ_X
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