Stuve-Wiedemann Syndrome (SWS) (OMIM #601559) is an autosomal recessive disorder characterized by skeletal changes, bowing of the lower limb, severe osteoporosis and joint contractures, episodic hyperthermia, frequent respiratory infections, feeding problems and high mortality in early life. It is caused by mutation in the leukemia inhibitory factor receptor gene (LIFR; 151443) on chromosome 5p13. We provide the clinical follow-up and molecular aspects of six new patients who carried the same novel mutation in the LIFR gene (p.Arg692X) and three patients carried a common haplotype at the LIFR locus supporting a founder effect in the Turkish population. The probable pathogenesis of the features is also discussed. Osseous findings in the presence of other above-mentioned morbid conditions should raise the suspicion of SWS in neonates especially in Arabic and Eastern Mediterranean countries with high rate of consanguineous marriages like in Turkey. Severe osteoporosis, bone deformities, milias, leukocoria, inflammatory lesions on distal extremities, tongue biting behavior and oral ulcers could be more prominent features of the survivors beyond the neonatal period while respiratory and feeding problems are remitting. It is of crucial importance to diagnose such babies earlier in order to prevent extensive laboratory workup and to provide proper genetic counseling.

Lipopolysaccharide (LPS), a major component of the outer membrane of Gram-negative bacteria, activates a broad spectrum of signaling pathways in immune cells. In this article, RAW264.7 cells have been stimulated for 4 h with 1 microg/mL of LPS in the presence or not of specific inhibitors of the NF-kappaB pathway (BAY 11-7082) and the PI3K pathway (LY294002). Gene expression profiles were characterized using the DNA microarray "Dual Chip Mouse Inflammation." This array monitors the expression of 233 genes encoding proteins playing a role in inflammation. Both signaling pathways exert an important role in the response to LPS, but they are not completely overlapping. For example, genes encoding the PAF receptor, PAI-1, PlA2 (group V), IL-13 receptor (alpha2), and GTP cyclohydrolase 1, were upregulated after LPS treatment, but this upregulation was counteracted by LY294002. The same was observed for BAY 11-7082: genes encoding the kit ligand, TLR2, or TNFRSF5 were mainly under the control of NF-kappaB. NF-kappaB plays an important role in the macrophage response to LPS, but we have also shown that the PI3K pathway partially contributes to it. Further experiments with the specific inhibitor of mTOR (rapamycin) will provide more information on the specific contribution of the PI3K/mTOR pathway in the inflammatory response in LPS-stimulated macrophages.

Homocysteine, derived from the metabolism of methionine, is claimed as a proatherogenic factor that leads to vascular dysfunction. To gain better insight into the molecular mechanisms involved, homocysteine was tested on a model of murine endothelial cells cultured in vitro, using a prototype DNA chip. The DNA chip was designed to follow the expression at the mRNA level of some major proinflammatory genes; TNF-alpha was used as a positive control.

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