Involvement of circulating CEA in liver metastases from colorectal cancers re-examined in a new experimental model.

Both experimental and clinical data show evidence of a correlation between elevated blood levels of carcinoembryonic antigen (CEA) and the development of liver metastases from colorectal carcinomas. However, a cause-effect relationship between these two observations has not been demonstrated. For this reason, we developed a new experimental model to evaluate the possible role of circulating CEA in the facilitation of liver metastases. A CEA-negative subclone from the human colon carcinoma cell line CO115 was transfected either with CEA-cDNA truncated at its 3' end by the deletion of 78 base pairs leading to the synthesis of a secreted form of CEA or with a full-length CEA-cDNA leading to the synthesis of the entire CEA molecule linked to the cell surface by a GPI anchor. Transfectants were selected either for their high CEA secretion (clone CO115-2C2 secreting up to 13 microg CEA per 10(6) cells within 72 h) or for their high CEA membrane expression (clone CO115-5F12 expressing up to 1 x 10(6) CEA molecules per cell). When grafted subcutaneously, CO115-2C2 cells gave rise to circulating CEA levels that were directly related to the tumour volume (from 100 to 1000 ng ml(-1) for tumours ranging from 100 to 1000 mm3), whereas no circulating CEA was detectable in CO115 and CO115-5F12 tumour-bearing mice. Three series of nude mice bearing a subcutaneous xenograft from either clone CO115-2C2 or the CO115-5F12 transfectant, or an untransfected CO115 xenograft, were further challenged for induction of experimental liver metastases by intrasplenic injection of three different CEA-expressing human colorectal carcinoma cell lines (LoVo, LS174T or CO112). The number and size of the liver metastases were shown to be independent of the circulating CEA levels induced by the subcutaneous CEA secreting clone (CO115-2C2), but they were directly related to the metastatic properties of the intrasplenically injected tumour cells.

Decision-theoretic analysis of forensic sampling criteria using Bayesian decision networks

Sampling issues represent a topic of ongoing interest to the forensic science community essentially because of their crucial role in laboratory planning and working protocols. For this purpose, forensic literature described thorough (Bayesian) probabilistic sampling approaches. These are now widely implemented in practice. They allow, for instance, to obtain probability statements that parameters of interest (e.g., the proportion of a seizure of items that present particular features, such as an illegal substance) satisfy particular criteria (e.g., a threshold or an otherwise limiting value). Currently, there are many approaches that allow one to derive probability statements relating to a population proportion, but questions on how a forensic decision maker - typically a client of a forensic examination or a scientist acting on behalf of a client - ought actually to decide about a proportion or a sample size, remained largely unexplored to date. The research presented here intends to address methodology from decision theory that may help to cope usefully with the wide range of sampling issues typically encountered in forensic science applications. The procedures explored in this paper enable scientists to address a variety of concepts such as the (net) value of sample information, the (expected) value of sample information or the (expected) decision loss. All of these aspects directly relate to questions that are regularly encountered in casework. Besides probability theory and Bayesian inference, the proposed approach requires some additional elements from decision theory that may increase the efforts needed for practical implementation. In view of this challenge, the present paper will emphasise the merits of graphical modelling concepts, such as decision trees and Bayesian decision networks. These can support forensic scientists in applying the methodology in practice. How this may be achieved is illustrated with several examples. The graphical devices invoked here also serve the purpose of supporting the discussion of the similarities, differences and complementary aspects of existing Bayesian probabilistic sampling criteria and the decision-theoretic approach proposed throughout this paper.

Die Arbeit: eine Re-Vision = Le travail: une re-vision

Was ist Arbeit? Ein notwendiges Übel, eine den Menschen erst zum Menschen machende Notwendigkeit, ein Mittel sich selbst zu verwirklichen, eine notwendige Struktur, die den Menschen gesund hält, ja sogar therapiert oder bloss eine unter vielen Möglichkeiten, mit dem Leben etwas anzufangen? Arbeit wurde schon immer mehrdeutig gefasst. Zwölf Autoren aus dem französischen und deutschen Kulturkreis diskutieren, was Arbeit ist und war. Die Beiträge aus Philosophie, Recht, Sozialwissenschaften, aber auch Kunstwissenschaften kreisen um vier wesentliche Spannungen des Begriffs Arbeit: die Arbeit der Frau, die Sichtbarkeit oder Sichtbarmachung der Arbeit, das Verhältnis von Arbeit zu anderen menschlichen Tätigkeiten, der Sinn und das Erleben der Arbeit mit dem allgegenwärtigen Stress, mit dem die heutige Arbeit verknüpft wird. Qu'est-ce que le travail? Un mal nécessaire, une nécessité pour faire des hommes des êtres humains, un moyen de se réaliser, une structure nécessaire qui maintient les êtres humains en santé, voire même les soigne, ou simplement une possibilité parmi d'autres de faire quelque chose de sa vie? Le terme de travail comprend un large éventail de significations. Douze auteurs de culture française et allemande discutent de ce qu'est le travail et de ce qu'il était. Les contributions issues de la philosophie, du droit, des sciences sociales, mais aussi des arts s'articulent autour de quatre dimensions essentielles du concept de travail: le travail des femmes, la visibilité ou la mise en évidence du travail, le lien entre le travail et les autres activités humaines, la recherche de sens et le vécu du travail avec le stress quotidien qui est aujourd'hui étroitement lié au travail.

Large multi-gene phylogenetic trees of the grasses (Poaceae): progress towards complete tribal and generic level sampling.

In this paper we included a very broad representation of grass family diversity (84% of tribes and 42% of genera). Phylogenetic inference was based on three plastid DNA regions rbcL, matK and trnL-F, using maximum parsimony and Bayesian methods. Our results resolved most of the subfamily relationships within the major clades (BEP and PACCMAD), which had previously been unclear, such as, among others the: (i) BEP and PACCMAD sister relationship, (ii) composition of clades and the sister-relationship of Ehrhartoideae and Bambusoideae + Pooideae, (iii) paraphyly of tribe Bambuseae, (iv) position of Gynerium as sister to Panicoideae, (v) phylogenetic position of Micrairoideae. With the presence of a relatively large amount of missing data, we were able to increase taxon sampling substantially in our analyses from 107 to 295 taxa. However, bootstrap support and to a lesser extent Bayesian inference posterior probabilities were generally lower in analyses involving missing data than those not including them. We produced a fully resolved phylogenetic summary tree for the grass family at subfamily level and indicated the most likely relationships of all included tribes in our analysis.

Abrupt decrease in serum testosterone levels after an oral glucose load in men: implications for screening for hypogonadism.

OBJECTIVE: This study examines the physiological impact of a glucose load on serum testosterone (T) levels in men with varying glucose tolerance (GT). DESIGN: Cross-sectional study. PATIENTS AND METHODS: 74 men (19-74 years, mean 51·4 ± 1·4 years) underwent a standard 75-g oral glucose tolerance test with blood sampling at 0, 30, 60, 90 and 120 min. Fasting serum glucose, insulin, total T (and calculated free T), LH, SHBG, leptin and cortisol were measured. RESULTS: 57% of the men had normal GT, 30% had impaired GT and 13% had newly diagnosed type 2 diabetes. Glucose ingestion was associated with a 25% decrease in mean T levels (delta = -4·2 ± 0·3 nm, P < 0·0001). T levels remained suppressed at 120 min compared with baseline (13·7 ± 0·6 vs 16·5 ± 0·7 nm, P < 0·0001) and did not differ across GT or BMI. Of the 66 men with normal T levels at baseline, 10 (15%) had levels that decreased to the hypogonadal range (<9·7 nm) at one or more time points. SHBG, LH and cortisol levels were unchanged. Leptin levels decreased from baseline at all time points (P < 0·0001). CONCLUSIONS: Glucose ingestion induces a significant reduction in total and free T levels in men, which is similar across the spectrum of glucose tolerance. This decrease in T appears to be because of a direct testicular defect, but the absence of compensatory changes in LH suggests an additional central component. Men found to have low nonfasting T levels should be re-evaluated in the fasting state.

An infrared reflection-absorption spectroscopic (IRRAS) study of the interaction of lipid A and lipopolysaccharide Re with endotoxin-binding proteins.

Lipopolysaccharides (LPS, endotoxins) are main constituents of the outer membranes of Gram-negative bacteria, with the 'endotoxic principle' lipid A anchoring LPS into the membrane. When LPS is removed from the bacteria by the action of the immune system or simply by cell dividing, it may interact strongly with immunocompetent cells such as mononuclear cells. This interaction may lead, depending on the LPS concentration, to beneficial (at low) or pathophysiological (at high concentrations) reactions, the latter frequently causing the septic shock syndrome. There is a variety of endogenous LPS-binding proteins. To this class belong lactoferrin (LF) and hemoglobin (Hb), which have been shown to suppress and enhance the LPS-induced cytokine secretion in mononuclear cells, respectively. To elucidate the interaction mechanisms of endotoxins with these proteins, we have investigated in an infrared reflection-absorption spectroscopy (IRRAS) study the interaction of LPS or lipid A monolayers at the air/water interface with LF and Hb proteins, injected into the aqueous subphase. The data are clearly indicative of completely different interaction mechanisms of the endotoxins with the proteins, with the LF acting only at the LPS backbone, whereas Hb incorporates into the lipid monolayer. These data allow an understanding of the different reactivities in the biomedicinal systems.

Spin-labeling coronary MR angiography with steady-state free precession and radial k-space sampling: initial results in healthy volunteers.

The purpose of this study was to prospectively compare free-breathing navigator-gated cardiac-triggered three-dimensional steady-state free precession (SSFP) spin-labeling coronary magnetic resonance (MR) angiography performed by using Cartesian k-space sampling with that performed by using radial k-space sampling. A new dedicated placement of the two-dimensional selective labeling pulse and an individually adjusted labeling delay time approved by the institutional review board were used. In 14 volunteers (eight men, six women; mean age, 28.8 years) who gave informed consent, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), vessel sharpness, vessel length, and subjective image quality were investigated. Differences between groups were analyzed with nonparametric tests (Wilcoxon, Pearson chi2). Radial imaging, as compared with Cartesian imaging, resulted in a significant reduction in the severity of motion artifacts, as well as an increase in SNR (26.9 vs 12.0, P < .05) in the coronary arteries and CNR (23.1 vs 8.8, P < .05) between the coronary arteries and the myocardium. A tendency toward improved vessel sharpness and vessel length was also found with radial imaging. Radial SSFP imaging is a promising technique for spin-labeling coronary MR angiography.