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Biomedical subjects

E Beutler

Publications and source records attributed to E Beutler.

At least 325 records · Page 18Linked to original sources
PubMed1982

alpha-Thalassemia: prevalence and hematologic findings in American Blacks.

alpha-Thalassemia is common in southeast Asia and the Mediterranean, where the predominant lesion seems to be a deletion of one or more of the four gene loci responsible for alpha-globin chain production. In the United States, the prevalence of alpha-thalassemia in blacks was once thought to be low, but more recent studies show that the prevalence of alpha-thalassemia is high. We measured the globin chain synthetic rations in 144 black Americans to determine the prevalence and hematologic manifestations of alpha-thalassemia in this population. There were 120 subjects with a mean synthetic ration of 0.986 +/- 0.04, with a range of 0.90 to 1.06; these were classified as normal. Five subjects were found to have beta-thalassemia; 19 subjects had mild alpha-thalassemia. The overall gene frequency for alpha-thalassemia was estimated to be 0.07 in this population. The hemoglobin values of subjects with mild alpha-thalassemia were not statistically significantly different from normal black or white control subjects of the same sex, but there was a significant decrease in the mean corpuscular volume and in the mean corpuscular hemoglobin value.

Adult↗
PubMed1982

G-6-PD Guadalajara. A new mutant associated with chronic nonspherocytic hemolytic anemia.

This paper describes a new G-6-PD variant designated Guadalajara, which was found in a Mexican boy suffering from chronic hemolytic anemia. The red cell enzyme activity of the subject is about 14%. The mutant enzyme showed rapid electrophoretic mobility, slightly increased affinity for glucose-6-phosphate, slightly decreased affinity for NADP+, moderately elevated utilization of substrate analogues, and normal heat stability, pH curve, and inhibition by NADPH. G-6-PD Guadalajara differs from all previously reported variants and is the first variant associated with chronic hemolysis found in Mexico.

Anemia, Hemolytic, Congenital↗
PubMed1982

Bone marrow transplantation in acute leukemia.

Bone marrow transplantation was initially introduced as a treatment modality for patients with acute leukemia who had failed all conventional treatment. When viewed within this context even the early results of bone marrow transplantation were encouraging. When transplantation was performed on patients with acute leukemia in first remission results clearly superior to the best currently obtainable with chemotherapy were documented. In this group of patients leukemic relapse is relatively unusual. Yet, some 40% of patients succumb, chiefly to graft-versus-host disease (GVHD). Current research efforts are aimed at blunting GVHD. They include the removal of T-lymphocytes from the transfused marrow by treatment with lectins and with antibodies. New immunosuppressive drugs may also prove helpful in improving the results obtained with bone marrow transplantation.

Acute Disease↗
PubMed1982

The osmotic fragility of erythrocytes after prolonged liquid storage and after reinfusion.

Although it is recognized that red cells lose membrane during storage, estimation of the osmotic fragility of erythrocytes has not previously proven to be a useful measurement of the storage lesion. Erythrocytes from blood stored in CPD-A2 were found to have a markedly increased osmotic fragility. A major portion of this increase was found to be due to accumulation of lactate, which is only slowly transported from within erythrocytes and which therefore exerts a strong osmotic effect in the usual osmotic fragility test. After an hour's incubation in a large volume of iso-osmotic buffer, the osmotic fragility curve of stored erythrocytes was much more nearly normal. Such cells were found to have a volume 5%--8% greater than that of normal cells, indicating that even after removal of lactate more osmotically active material was present in the stored erythrocytes than in fresh cells. Most of this differences can be accounted for by substitution of chloride ion for 2,3-DPG, since chloride exerts approximately 3.7 times the osmotic effect of 2,3-DPG per unit charge. In addition to the shift in osmotic fragility produced by the increased intracellular osmotically active material, a "fragile tail" of red cells was also present. Stored erythrocytes were labeled with 51Cr and reinfused into the volunteer donors. The osmotic fragility of the reinfused cells was estimated using a technique of sequential osmotic hemolysis that permitted accurate estimation of osmotic fragility of transfused cells using very small amounts of 51Cr. The osmotic fragility of the reinfused cells became less than those of fresh cells after 24 hr and was exactly the same as those of fresh cells after 4 days. The fragile tail disappeared at a rate that approximated the rate of loss of nonviable erythrocytes from the circulation as measured by 51Cr. These findings are consistent with the preferential destruction of a subpopulation of red cells with a diminished surface area.

Adenine↗
PubMed1982

Gaucher disease: a century of delineation and research. Enzyme replacement therapy: model and clinical studies.

A number of investigators have attempted to treat Gaucher disease with exogenous glucocerebrosidase. Although at times encouraging biochemical changes and suggestive alterations in organomegaly have been reported, overall, the results of enzyme replacement therapy must be judged to be a failure. In order to understand this lack of success with a promising treatment modality, four aspects of enzyme replacement therapy require examination: 1. The purification of glucocerebrosidase to a form which can hydrolyze glucocerebroside under in vivo conditions; 2. The delivery of the enzyme to cells of the macrophage-monocyte system; 3. The intracellular fate of the administered enzyme; 4. The capacity of the enzyme to effectively contact intracellular glycolipid deposits. A model system for the study of the latter three of these aspects of enzyme replacement therapy has been developed. Monocytes from normal subjects and patients with Gaucher disease were maintained in tissue culture for several months using horse serum-containing culture media. When such cells were "fed" glucocerebrosidase, their enzyme deficiency was corrected for at least 72 hours. Cells from Gaucher disease patients do not spontaneously accumulate glucocerebroside in this system. When loaded with 14C-labeled glucocerebroside, they do not become Gaucher cells but rather manifest a remarkable capacity to catabolize glucocerebroside, so that the labeled fatty acid quickly appears in neutral fats and in phospholipids. Therefore, this model is not yet suitable for study of the effectiveness of enzyme therapy.

Cells, Cultured↗
PubMed1981

Studies on glutathione transport utilizing inside-out vesicles prepared from human erythrocytes.

Adenosine triphosphate-dependent glutathione transport was characterized using inside-out vesicles made from human erythrocytes. Kinetic analysis of the glutathione disulfide (GSSG) transport showed a biphasic Lineweaver-Burk plot as a function of GSSG concentration suggesting the operation of two different processes. One phase had a high affinity for GSSG and a low transport velocity. Most active at acidic pH and at 25 degrees C, this transport activity was easily lost during the storage of vesicles at 4 degrees C. The Km for Mg-ATP was 0.63 mM; guanosine triphosphate (GTP) substituted for ATP gave a 340% stimulation fo transport activity. Neither dithiothreitol nor thiol reagents affected this transport process. The other phase had a low affinity for GSSG and a high transport velocity. Most active at pH 7.2 and 37 degrees C, this transport activity was stable during storage of vesicles at 4 degrees C for several days. The Km for Mg-ATP was 1.25 mM; GTP substituted with no change in activity. Dithiothreitol increased the V but did not alter the Km, and thiol reagents inhibited the transport. These findings suggest that there are two independent transfer processes for GSSG in human erythrocytes.

Adenosine Triphosphatases↗
PubMed1981

A common mutant EcoRI restriction endonuclease site in the 5' flanking portion of the human alpha-globin gene.

A mutant EcoRI endonuclease restriction site has been identified in 3 of 37 Black subjects and in 2 sibs of one of these persons. This mutation was not encountered in 13 Whites. It is located approximately 6 kilobases "inside" the normal site in the 5' flanking sequence of the alpha-globin chain complex. The shortened alpha-globin gene-bearing segment produced in the EcoRI digest produces a restriction map similar to that observed for the common alpha-globin gene deletion observed in the Black population. However, the restriction map with BamHI is normal, confirming that all four alpha loci are present.

Base Sequence↗
PubMed1981

A simple and rapid method for determination of G gamma:A gamma globin chain synthetic ratio.

A simple and rapid method for the determination of the G gamma- to A gamma-globin chain relative synthetic ratios is described. This technic uses 35S-methionine as the labeled amino acid and introduces a simple procedure for Hb-F purification. The chain separation is based on slab gel isoelectric focusing, and the gel after visualization of protein bands without staining is cut and solubilized in periodic acid, and the radioactivity is counted. This method can be applied in blood samples with low Hb-F levels, and as many as 20 samples can be analyzed at one time. The method was found to yield the expected synthetic ratio, and its reproducibility and repeatability were found to be high.

Fetal Blood↗
PubMed1981

Falsely normal value in fluorometric transferase screening of galactosemic blood. A cautionary note.

A blood sample from a galactosemic infant gave a normal result with the fluorescent screening test for galactose-1-phosphate uridyl transferase. The generation of fluorescence from this sample was found to be property of the plasma; the erythrocytes manifested no galactose-1-phosphate uridyl transferase activity. The plasma was found to contain a high level of isocitrate dehydrogenase, presumably a result of the infant's liver disease, and of isocitrate, presumably derived from citrate in the anticoagulant solution by action of aconitase derived from leukocytes which lysed during shipment. The oxidation of the isocitrate by the dehydrogenase apparently resulted in reduction of NADP to NADPH. False negative results have not been reported previously using the fluorescent transferase assay. They can be avoided in the future by using EDTA rather than citrate as an anticoagulant, particularly if blood samples are to be shipped at ambient temperature.

False Negative Reactions↗