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G. We (g + we)

Distribution by Scientific Domains

Medical Sciences	50%

Selected Abstracts

The ,670A > G polymorphism in the promoter region of the FAS gene is associated with necrosis in periportal areas in patients with chronic hepatitis C

JOURNAL OF VIRAL HEPATITIS, Issue 6 2005
J. Aguilar-Reina
Summary., Evidence suggests that apoptosis of liver cells may play a significant role in the pathogenesis of hepatitis C virus (HCV) infection. One of the best characterized apoptotic pathway is that mediated by the death receptor Fas. Fas expression has been found to be up-regulated on hepatocytes in chronic HCV infection, particularly in periportal areas. Recently, two polymorphisms have been identified in the promotor region of the FAS gene, ,1377G > A and ,670A > G. We have evaluated the involvement of these variants in the susceptibility to HCV infection, the severity of liver damage and progression of fibrosis in chronic hepatitis C. A cohort of 197 patients with chronic hepatitis C and 100 controls were analysed for both polymorphisms by Fluorescence Resonance Energy Transfer using specific probes and the LightcyclerTM system. In addition, liver biopsies were taken in 167 patients and scored using the Knodell classification system. We have found that the allele frequencies and the distribution of both polymorphisms do not differ significantly in the HCV cohort and in the control population. Thus, none of the polymorphisms seems to be related with susceptibility to HCV infection. However, we have examined the possible association between the two variants and the grade of necroinflammatory activity and the stage of fibrosis and we have detected an under-representation of the ,670A > G variant among those patients with higher Knodell's scores (P = 0.049) and necroinflammatory activity (P = 0.036). The ,670A allele was associated with higher levels of periportal necrosis (P = 0.012). In conclusion, our findings suggest an association between the ,670A > G polymorphism and the grade of necrosis in periportal areas in patients with chronic hepatitis C. [source]

Protease inhibitors derived from elafin and SLPI and engineered to have enhanced specificity towards neutrophil serine proteases

PROTEIN SCIENCE, Issue 3 2009
Marie-Louise Zani
Abstract The secretory leukocyte protease inhibitor (SLPI), elafin, and its biologically active precursor trappin-2 are endogeneous low-molecular weight inhibitors of the chelonianin family that control the enzymatic activity of neutrophil serine proteases (NSPs) like elastase, proteinase 3, and cathepsin G. These inhibitors may be of therapeutic value, since unregulated NSP activities are linked to inflammatory lung diseases. However SLPI inhibits elastase and cathepsin G but not proteinase 3, while elafin targets elastase and proteinase 3 but not cathepsin G. We have used two strategies to design polyvalent inhibitors of NSPs that target all three NSPs and may be used in the aerosol-based treatment of inflammatory lung diseases. First, we fused the elafin domain with the second inhibitory domain of SLPI to produce recombinant chimeras that had the inhibitory properties of both parent molecules. Second, we generated the trappin-2 variant, trappin-2 A62L, in which the P1 residue Ala is replaced by Leu, as in the corresponding position in SLPI domain 2. The chimera inhibitors and trappin-2 A62L are tight-binding inhibitors of all three NSPs with subnanomolar Kis, similar to those of the parent molecules for their respective target proteases. We have also shown that these molecules inhibit the neutrophil membrane-bound forms of all three NSPs. The trappin-2 A62L and elafin-SLPI chimeras, like wild-type elafin and trappin-2, can be covalently cross-linked to fibronectin or elastin by a tissue transglutaminase, while retaining their polypotent inhibition of NSPs. Therefore, the inhibitors described herein have the appropriate properties to be further evaluated as therapeutic anti-inflammatory agents. [source]

Properly colored subgraphs and rainbow subgraphs in edge-colorings with local constraints

RANDOM STRUCTURES AND ALGORITHMS, Issue 4 2003
Noga Alon
We consider a canonical Ramsey type problem. An edge-coloring of a graph is called m-good if each color appears at most m times at each vertex. Fixing a graph G and a positive integer m, let f(m, G) denote the smallest n such that every m -good edge-coloring of Kn yields a properly edge-colored copy of G, and let g(m, G) denote the smallest n such that every m -good edge-coloring of Kn yields a rainbow copy of G. We give bounds on f(m, G) and g(m, G). For complete graphs G = Kt, we have c1mt2/ln t , f(m, Kt) , c2mt2, and cmt3/ln t , g(m, Kt) , cmt3/ln t, where c1, c2, c, c are absolute constants. We also give bounds on f(m, G) and g(m, G) for general graphs G in terms of degrees in G. In particular, we show that for fixed m and d, and all sufficiently large n compared to m and d, f(m, G) = n for all graphs G with n vertices and maximum degree at most d. © 2003 Wiley Periodicals, Inc. Random Struct. Alg., 2003 [source]

Breastfeeding duration and exclusivity associated with infants' health and growth: data from a prospective cohort study in Bavaria, Germany

ACTA PAEDIATRICA, Issue 6 2009
Barbara Rebhan
Abstract Aim: To investigate the relationship between breastfeeding and infant health and to describe growth in the first 9 months. Methods: Mothers delivering a baby in April 2005 were recruited throughout Bavaria, Germany, for a prospective birth cohort study. These mothers reported breastfeeding data, health and growth data of 1901 infants assessed by a physician in questionnaires on day 2,6, and in months 2, 4, 6 and 9. Subjects were healthy term infants with a birth weight ,2500 g. We compared 475 infants breastfed exclusively for ,6 months (group A), 870 infants breastfed fully/exclusively ,4 months, but not exclusively ,6 months (group B) and 619 infants not breastfed/breastfed <4 months (group C). Results: In multivariate analysis ,6 months of exclusive breastfeeding reduced significantly the risk for ,1 episode of gastrointestinal infection(s) during months 1,9 compared to no/<4 months breastfeeding (adjusted odds ratio [OR]: 0.60; 95% confidence interval [CI]: 0.44,0.82). The application of the World Health Organization (WHO) , child growth standards showed lower weight-for-length z-scores in first days of life in group C versus groups A and B, whereas in months 6/7 group C showed the highest scores. Conclusion: Differences in child growth depending on breastfeeding duration should be investigated further. Concerning health outcomes our findings support the recommendation for ,6 months of exclusive breastfeeding. [source]