Morphometric Processing of Sounding Profiles and Comparison with Visual Analysis

Morphometric analysis based on data processing of sounding profiles is presented in this study. The process involves segmentation of profiles so that units of equal length are dealt with, and calculation of the following characteristic parameters : maximum amplitude — relief — ruggedness of bottom features. The programme developed is applied in the study of 21 sounding profiles recorded between the shore and an offshore depth of 25 m, south of the Gironde estuary (S.W. France). The quantitative results are compared with visual analysis of the echograms. Comparison of the various charts obtained (figs. 1,9, 10 and 11) shows that the results are complementary. Visual analysis has a higher power of resolution and enables areas of strikingly contrasting morphology to be rapidly located. Quantitative analysis enables the undersea features to be strictly classified, even in complex areas where the eye cannot distinguish the many shades of difference. This process has been conceived to define the characteristics of the superficial physical structure of the sea floor, but use of a digital sounder seems necessary if the process is to be developed and its use to become accepted

Differential regulation of cell proliferation and protease secretion by epidermal growth factor and amphiregulin in tumoral versus normal breast epithelial cells

Amphiregulin (AR) is a heparin-binding epidermal growth factor (EGF)-related peptide that seems to play an important role in mammary epithelial cell growth regulation. We have investigated the regulation of AR-gene expression and -protein secretion by EGF in normal breast epithelial cells (HMECs), as well as in the tumoral breast epithelial cell lines MCF-7 and MDA-MB231. EGF induced a dose-dependent increase of AR mRNA level in both normal and tumoral cells. Thus, 10−8M EGF stimulated AR expression in HMECs to 140–300% of control. A similar EGF concentration increased AR mRNA level to 550% and 980% of control in MCF-7 and MDA-MB231 cells, respectively. This was accompanied by an accumulation of AR into conditioned culture media. However, HMECs secreted in response to EGF, 5–10 fold more AR than tumour cells. Furthermore, the potential participation of AR in the regulation of the plasminogen activator (PA)/plasmin system was investigated. Whereas HMEC-proliferation was stimulated by AR, the levels of secreted urokinase-type plasminogen activator (uPA) and type-1 plasminogen activator inhibitor (PAi-1) remained unaffected. Conversely, AR failed to regulate the proliferation of tumoral cell lines but induced an accumulation of uPA and PAi-1 into culture media. This was accompanied by an increase of the number of tumoral cells that invaded matrigel in vitro. Moreover, the presence of a neutralizing anti-uPA receptor antibody reversed the increased invasiveness of MDA-MB231 cells induced by AR. These data reveal differential behaviour of normal versus tumoral breast epithelial cells in regard to the action of AR and demonstrate that, in a number of cases, AR might play a significant role in tumour progression through the regulation of the PA/plasmin system. © 2001 Cancer Research Campaign http://www.bjcancer.co

Determination of TGFβ1 protein level in human primary breast cancers and its relationship with survival

Transforming growth factor-beta (TGFβ)1 is thought to be implicated in breast cancer progression. However, data about the influence of TGFβ1 on breast cancer development are conflicting. To clarify the clinical relevance of TGFβ1, TGFβ1 protein level has been measured by enzyme-immoassay in 193 breast tumour samples. We found that 94.3% of patients expressed TGFβ1 with a range of 0–684 pg mg−1 protein. In the overall population, an increase of tumoral TGFβ1 was observed in premenopausal patients when compared to postmenopausal subgroup (P=0.0006). When patients were subdivided according to nodal status, TGFβ1 was correlated to type-1 plasminogen activator inhibitor in the node-negative subgroup (P=0.040). Multivariate analysis revealed that, after lymph node status (P=0.0002) and urokinase-type plasminogen activator (P=0.004), TGFβ1 was an independent prognostic marker for DFS (P=0.005) in the overall population. In the node-negative population, TGFβ1 was the prominent prognostic factor (P=0.010). In the same population, Kaplan–Meier curves demonstrated that high TGFβ1 level was correlated with a shorter disease-free survival (P=0.020). These data suggest that the measurement of tumoral TGFβ1 protein level, especially for node-negative patients, might help to identify a high-risk population early in tumour progression

Avoiding false-positive signals with nuclease-vulnerable molecular beacons in single living cells

There have been a growing number of studies where molecular beacons (MBs) are used to image RNA expression in living cells; however, the ability to make accurate measurements can be hampered by the generation of false-positive signals resulting from non-specific interactions and/or nuclease degradation. In the present study, we found that such non-specific signals only arise in the nucleus of living cells. When MBs are retained in the cytoplasmic compartment, by linking them to quantum dots (QDs), false-positive signals are reduced to marginal levels. Consequently, MB–QD conjugates were used to measure the expression of the endogenous proto-oncogene c-myc in MCF-7 breast cancer cells by quantifying the total fluorescent signal emanating from individual cells. Upon the addition of tamoxifen, measurements of MB fluorescence indicated a 71% reduction in c-myc expression, which correlated well with RT-PCR measurements. Variations in MB fluorescence resulting from instrumental fluctuations were accounted for by imaging fluorescent calibration standards on a daily basis. Further, it was established that measurements of the total fluorescent signal were not sensitive to the focal plane. Overall, these results provide evidence that accurate measurements of RNA levels can be made when MBs are retained in the cytoplasm

Differential regulation of specific genes in MCF-7 and the ICI 182780-resistant cell line MCF-7/182R-6

To elucidate the mechanisms involved in anti-oestrogen resistance, two human breast cancer cell lines MCF-7 and the ICI 182780-resistant cell line, MCF-7/182R-6, have been compared with regard to oestrogen receptor (ER) expression, ER function, ER regulation, growth requirements and differentially expressed gene products. MCF-7/182R-6 cells express a reduced level of ER protein. The ER protein is functional with respect to binding of oestradiol and the anti-oestrogens tamoxifen, 4-hydroxy-tamoxifen and ICI 182780, whereas expression and oestrogen induction of the progesterone receptor is lost in MCF-7/182R-6 cells. The ER protein and the ER mRNA are regulated similarly in the two cell lines when subjected to treatment with oestradiol or ICI 182780. Oestradiol down-regulates ER mRNA and ER protein expression. ICI 182780 has no initial effect on ER mRNA expression whereas the ER protein level decreases rapidly in cells treated with ICI 182780, indicating a severely decreased stability of the ER protein when bound to ICI 182780. In vitro growth experiments revealed that the ICI 182780-resistant cell line had evolved to an oestradiol-independent phenotype, able to grow with close to maximal growth rate both in the absence of oestradiol and in the presence of ICI 182780. Comparison of gene expression between the two cell lines revealed relatively few differences, indicating that a limited number of changes is involved in the development of anti-oestrogen resistance. Identification of the differentially expressed gene products are currently in progress. © 1999 Cancer Research Campaig

Characterization and dating of coastal deposits of NW Portugal (Minho - Neiva area): a record of climate, eustasy and crustal uplift during the Quaternary

This study presents the characterization and numerical dating of Quaternary coastal deposits of NW Portugal, located between the mouths of the Minho and Neiva rivers. They record continental (small alluvial fans and streams) and transitional (aeolian dunes, interdune ponds, estuary, sandy and gravelly beaches) paleoenvironments. Quartz and K-feldspar optically stimulated luminescence (OSL) dating is employed as well as AMS C-14 dating. A staircase of coastal terraces (abrasion shore platforms) was identified (altimetry, a.s.l.) and ascribed to the following probable Marine Isotope Stages (MIS): T1 - 20-18 m (MIS11); T2 - ca. 13 m (MIS9); T3 - 9.3-7.3 m (MIS7); T4 - 5.5-4.5 m (MIS5); T5 - 3.5-2.0 m (MIS5). The terraces have some preserved sedimentary facies that includes coeval beach sediments on the lowest four. A late Pleistocene to Holocene sedimentary cover comprises four sub-units: a) the lower sub-unit, corresponding to ferruginous stream deposits and aeolian dunes dated ca. 67-61 ka (MIS4), probably related with sub-humid to arid mid-cold conditions; b) on the slopes, the lower sub-unit is overlapped by sandy-silty colluvium and sandy alluvial deposits dated ca. 56-28 ka (MIS3) and probably reflecting cold/mid-cold and wet/dry climate conditions; c) this sub-unit is topped by soliflucted lobes and sandy-silty/silty deposits recording cold and dry climate dated 20-13 ka (MIS2), and d) a top subunit dated to 16-18th century, recording Little Ice Age events, consisting of fluvial sediments coeval with temperate climate evolving to aeolian dunes from the Maunder Minimum (cold windy dry conditions).Portuguese Foundation for Science and Technology (FCT) - grant SFRH/BD/16438/2004 - project PTDC/GEO-GEO/2860/2012 - Sabbatical Leave Grant ref. SFRH/BSAB/1289/2012 - Research also has been supported by both Aarhus University and Risø DTU (Denmark