No abstract

Both stem cells and mast cells express c-kit and proliferate after exposure to c-kit ligand. Mutations in c-kit may enhance or interfere with the ability of c-kit receptor to initiate the intracellular pathways resulting in cell proliferation. These observations suggested to us that mastocytosis might in some patients result from mutations in c-kit. cDNA synthesized from peripheral blood mononuclear cells of patients with indolent mastocytosis, mastocytosis with an associated hematologic disorder, aggressive mastocytosis, solitary mastocytoma, and chronic myelomonocytic leukemia unassociated with mastocytosis was thus screened for a mutation of c-kit. This analysis revealed that four of four mastocytosis patients with an associated hematologic disorder with predominantly myelodysplastic features had an A-->T substitution at nt 2468 of c-kit mRNA that causes an Asp-816-->Val substitution. One of one patient examined who had mastocytosis with an associated hematologic disorder had the corresponding mutation in genomic DNA. Identical or similar amino acid substitutions in mast cell lines result in ligand-independent autophosphorylation of the c-kit receptor. This mutation was not identified in the patients within the other disease categories or in 67 of 67 controls. The identification of the point mutation Asp816Val in c-kit in patients with mastocytosis with an associated hematologic disorder provides insight not only into the pathogenesis of this form of mastocytosis but also into how hematopoiesis may become dysregulated and may serve to provide a means of confirming the diagnosis, assessing prognosis, and developing intervention strategies.

No abstract

Total and visceral adipose-tissue (AT) volumes were determined by computed tomography (CT) by a multiscan technique in 17 men and 10 women with a wide range of body weights. In these primary materials, weight, height, and various diameters, circumferences, and subcutaneous AT thicknesses of the trunk were examined for their relationships to CT-determined total and visceral AT volumes. Predictive AT equations from the primary materials were then tested on two cross-validation groups consisting of another 7 men and 9 women. For the prediction of the total AT volume, weight/height was the superior single predictor, with errors less than 11% in primary and cross-validation materials. For the prediction of visceral AT volume, simple equations based entirely on the sagittal diameter of the trunk at the L3-L5 level resulted in errors less than 21% in both sexes.