MYH9 spectrum of autosomal-dominant giant platelet syndromes: unexpected association with fibulin-1 variant-D inactivation.

The autosomal-dominant giant platelet syndromes (Fechtner, Epstein, and Sebastian platelet syndromes and May-Hegglin anomaly) represent a group of disorders characterized by variable degrees of macrothrombocytopenia with further combinations of neutrophil inclusion bodies and Alport-like syndrome manifestations, namely, deafness, renal disease, and eye abnormalities. The disease-causing gene of these giant platelet syndromes was previously mapped by us to chromosome 22. Following their successful mapping, these syndromes were shown to represent a broad phenotypic spectrum of disorders caused by different mutations in the nonmuscle myosin heavy chain 9 gene (MYH9).

MAP kinase activation by mu opioid receptor in cord blood CD34(+)CD38(-) cells.

Objective: Opioid receptor expression and function traditionally have been studied in neuronal cells and recently in mature lymphoid cells; however, little is known about their possible functions in hematopoietic stem cells (CD34(+) cells). We studied the expression of the mu receptor on CD34(+) cells and assessed the signal transduction cascade it induces.

Materials And Methods: Mu-receptor expression on cord blood (CB) and peripheral blood (PB) CD34(+) cells was studied by microarrays, immunostaining, and fluorescence-activated cell sorting analysis.

Activated macrophages for treating skin ulceration: gene expression in human monocytes after hypo-osmotic shock.

Macrophages play a major role in almost all stages of the complex process of wound healing. It has been previously shown that the incorporation of a hypo-osmotic shock step, in the process of monocyte-concentrate preparation from a blood unit, induces monocyte/macrophage activation. As the macrophages are produced using a unique, closed and sterile system, they are suitable for local application on ulcers in elderly and paraplegic patients.

A positive feedback mechanism in the transcriptional activation of Apaf-1 by p53 and the coactivator Zac-1.

p53 exerts its tumor suppressor effects by activating genes involved in cell growth arrest and programmed cell death. The p53 target genes inducing growth arrest are well defined whereas those inducing apoptosis are not fully characterized. Proapoptotic activity of p53 was shown to involve several genes like Bax, Noxa and Puma, which may function in the release of cytochrome c from the mitochondria.

Nonmuscle myosin heavy chain IIA mutations define a spectrum of autosomal dominant macrothrombocytopenias: May-Hegglin anomaly and Fechtner, Sebastian, Epstein, and Alport-like syndromes.

May-Hegglin anomaly (MHA) and Fechtner (FTNS) and Sebastian (SBS) syndromes are autosomal dominant platelet disorders that share macrothrombocytopenia and characteristic leukocyte inclusions. FTNS has the additional clinical features of nephritis, deafness, and cataracts. Previously, mutations in the nonmuscle myosin heavy chain 9 gene (MYH9), which encodes nonmuscle myosin heavy chain IIA (MYHIIA), were identified in all three disorders.