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J Glass

Publications and source records attributed to J Glass.

142 records · Page 8Linked to original sources
PubMed1976

Erythroid cell differentiation.

We have reviewed erythroid cell differentiation from two points of view: 1) differences between fetal and adult human red cells with particular reference to alterations which can occur in the normal pattern of erythroid cell development during the course of leukemia; 2) beochemical events which occur during erythroid cell maturation, as a model system for the study of the control of gene expression. During the course of many leukemias there is the synthesis of red cells containing fetal hemoglobin. In most cases this phenomenon is limited to a small population or clone of red cells and probably represents a nonspecific response of the bone marrow to a hematologic stress. However, in juvenile chronic myeloid leukemia and, in rare cases of erythroleukemia, there is a major reversion to fetal erythropoiesis, with progressive increase in fetal hemoglobin levels and synthesis of red cells which contain not only fetal hemoglobin but have a true fetal pattern of protein synthesis affecting proteins other than Hb F, namely Hb A2, carbonic anhydrase and the membrane antigens i and I. In this case, the fetal erythropoiesis may be a more specific manifestation of the leukemic process and may be related to the phenomenon of fetal protein synthesis (alpha-fetoprotein of carcinoembryonic antigen) observed in other types of neoplasia. Further information on the etiology and pathogenesis of abnormal cell proliferation and differentiation in the leukemias can be obtained by the study of experimental systems permitting the investigation of the regulation of gene expression in differentiating mammalian cells. Maturing erythroid cells provide a promising system for such investigations for many reasons: differentiating erythroid cells can be obtained relatively free of other cell types; a large amount of a well characterized product, hemoglobin, is synthesized; techniques are now available that permit isolation of erythroid precursors at different stages of differentiation (5-8); and finally, highly sensitive methods of measuring globin mRNA levels by DNA-RNA hybridization are currently available (13, 26, 27). We have used such techniques to measure levels of globin mRNA in separated populations of murine erythroid cells at different stages of maturation. These studies demonstrated a correlation between globin mRNA content and degree of morphological maturation. In the least well differentiated cells, however, there appeared to be a disproportionate amount of mRNA for the level of hemoglobin synthesis in these cells. These results suggest the presence of some translational control of globin mRNA in the early stages of erythroid development, although the major control of globin gene expression in this system seems to be at the transcriptional level...

Anemia, Hemolytic↗
PubMed1975

Pharmacokinetic studies of tolmetin in man.

The pharmacokinetics of the new anti-inflammatory agent tolmetin have been studied after its oral administration to normal subjects and to patients with rheumatoid arthritis. Plasma concentration-time data were fitted to a one-compartment open model. Following single oral doses, no basic differences in rates of drug absorption and elimination were found between normal subjects and arthritic patients. For the 12 subjects studied, the overall mean elimination rate constant was 0.839 hr-1, corresponding to a plasma half-life of 0.83 hr. The drug was rapidly absorbed and had a mean apparent volume of distribution of 0.098 l/kg. Plasma levels and pharmacokinetic parameters of tolmetin in arthritic patients after multiple dosing were smaller to those after a single dose.

Adult↗
PubMed1975

Studies of murine erythroid cell development. Synthesis of heme and hemoglobin.

Techniques of cell separation were used to isolate murine erythroid precursors at different states of maturation. Cells were studied before and after short-term incubation in the presence or absence of erythropoietin. Complementary results were obtained by direct examination of the cell fractions and by the short-term culture experiments. Indices of heme synthesis, including incorporation of 59Fe or [2-14C]glycine into heme and activity of delta-aminolevulinic acid synthetase, were already well developed in the least mature cells, chiefly pronormoblasts. Activity then rose moderately in the cell fractions consisting primarily of basophilic and polychromatophilic normoblasts, and fell off with further increases in cell maturity. On short-term culture in the presence of erythropoietin, activity declined with increasing cell maturation except in the least mature fraction where the original level of activity was maintained. By contrast, synthesis of labeled hemoglobin ([3H]leucine) was very low in the least mature cell fractions and rose progressively with increasing cell maturity. The rate of hemoglobin synthesis increase in cells at all stages of maturation when cultured in the presence of erythropoietin. Despite the different patterns observed for heme synthesis and hemoglobin synthesis, both synthetic activities were consistently higher in cells cultured with erythropoietin as compared to controls. These findings suggest that erythropoietin stimulates biochemical differentiation of erythroid precursors at various stages of maturation. They also demonstrate an asynchronism between heme synthesis and hemoglobin syhthesis; heme synthesis is already well developed in the least mature erythroid cells and begins to diminish as the capacity for hemoglobin synthesis continues to rise.

5-Aminolevulinate Synthetase↗
PubMed1975

Use of cell separation and short-term culture techniques to study erythroid cell development.

Cell populations highly enriched for the different stages of erythroid cell maturation were obtained by three sequential operations: harvesting of erythroid cells after induction of erythroid hyperplasia in the spleens of mice, elimination of the more mature erythrocytes by immunologic techniques, and separation of the residual nucleated erythroid cells as a function of size by the velocity sedimentation technique. The resulting cell fractions were studied both directly and after overnight incubation in the presence or absence of erythropoietin. In short-term culture, erythropoietin stimulated proliferation of pronormoblasts and basophilic normoblasts but probably not cells at later stages of differentiation. Erythropoietin also appeared to recruit increased numbers of pronormoblasts. In this experimental system, erythroid cell differentiation was able to proceed in the absence of erythropoietin, but without proliferation of these early erythroid cells. These techniques have provided a model system for the study of erythroid cells at different stages of maturation isolated from a uniform source at one point in time. The morphologic observations indicated that erythropoietin stimulates erythroid cell proliferation at several early stages of the maturation pathway.

Anemia, Hemolytic↗
PubMedDate not supplied

Case report: Thymectomy-induced remission of acquired autoimmune hemolytic anemia in an adult with myasthenia gravis.

A 57-year-old woman with diabetes mellitus, hypothyroidism, idiopathic thrombocytopenic purpura, myasthenia gravis, systemic lupus erythematosus, atopy, and basal cell cancer of the skin developed a severe Coombs'-positive autoimmune hemolytic anemia which was resistant to treatment with large doses of azathioprine, cytoxan, and prednisone. One year after transcervical thymectomy the hemolytic anemia disappeared and the patient has maintained a normal hemoglobin and negative Coombs' test without immunosuppressants even since. We believe this case report to be the first recorded instance of thymectomy-induced remission of autoimmune hemolytic anemia in an adult.

Anemia, Hemolytic, Autoimmune↗