Bernard-Soulier syndrome is a constitutional thrombopathy with an impaired platelet adhesion to the vessel wall. Since the first description in 1948 many works had been reported, and recently a molecular abnormality of the platelet membrane was shown. Interactions between specific membrane sites and platelet functions are now proposed.
In vitro granulocyte colony formation has been studied using the methylcellulose system in 22 children with neuroblastoma, 13 of them having bone marrow invasion. Only one third exhibited normal results. There were various disturbances of granulopoiesis in vitro: colony forming cells were decreased or increased and in the amplification compartment either an ineffective leucopoiesis or an increase in the number of mitosis was present. The abnormalities are not correlated to bone marrow invasion.
The hypothesis is proposed that regulation of hemopoiesis is largely accomplished by expansion or contraction of the committed stem cell compartments and that pluripotential stem cells are normally not involved or in cycle. The thesis appears supported by the fact that erythropoietin affects the committed red cell precursors, that 98% of marrow mitoses have been shown to occur in cells clearly recognizable as red or white cell precursors (while the pluripotential stem cells by definition are not so recognizable), and that it has been shown (by the spleen nodule assay) that the pluripotential stem cell compartment in the marrow cannot be readily expanded. The major objection to the proposed hypothesis are tritiated thymidine suicide data, which suggest that up to 20% of pluripotential stem cells may be constantly in cycle in some stains of mice. Preliminary experimental evidence supporting the hypothesis has been obtained: normal pluripotential stem cells which transfused into normal isologous mice are not lost as has been assumed but proliferate after irradiation, suggesting that it takes a special stimulus to "turn-on" the normally quiescent pluripotential stem cells.
The structural and functional abnormalities of erythrocyte membrane proteins in hereditary hemolytic anemias are reviewed. The authors stress the problems of protein solubilization and the artefacts of the sodium dodecylsulphate polyacrylamide gel electrophoresis; protein abnormalities observed with that method are inconstant and non-specific. Abnormal "spectrin" has been reported in hereditary spherocytosis: however analysis of purified spectrin peptides by isoelectric focusing in 8M urea did not reveal any difference between normal and hereditary spherocytosis spectrin. Deficient autophosphorylation of erythrocyte membrane proteins by endogenous membrane protein-kinases 3'5-cyclic-AMP dependent and independent was pointed out in hereditary spherocytosis and stomatocytosis: the authors' experience was contrary to such results: quantitatively and qualitatively normal activity of membrane protein-kinase was found in five cases of hereditary spherocytosis. The authenticity, frequency and specificity of the various membrane protein abnormalities reported so far, are not firmly established. Many insufficiently verified results published prematurely have been later denied. To date no membrane protein anomaly may be considered as a biochemical cause of any type of hereditary hemolytic anemia.
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