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Biomedical subjects

H F Bunn

Publications and source records attributed to H F Bunn.

At least 109 records · Page 6Linked to original sources
PubMed1981

Clinical consequences of acquired transfusional iron overload in adults.

We assessed the clinical sequelae of transfusional iron overload in 15 nonthalassemic adults (40 to 71 years of age) with anemias requiring transfusions. Iron loading had been present for less than four years in 14 patients. The number of units of blood transfused ranged from 60 to 210 (mean, 120). Liver-biopsy specimens in 10 patients contained seven to 26 times the normal amount of iron and typically showed focal portal fibrosis. Left ventricular cardiac function was impaired in only the most heavily transfused patients or in those with coexisting coronary-artery disease, All patients had glucose intolerance associated with significantly reduced insulin output, compared with controls (P < 0.01). Pituitary reserve of ACTH was limited in 10 of 12 patients, and that of gonadotropin in five of 13. We conclude that widespread subclinical organ dysfunction can result from transfusional iron overload developing in adulthood. The pattern of organ involvement resembles that encountered in idiopathic hemochromatosis.

Adult↗
PubMed1981

The effect of erythrocyte membrane preparations on the polymerization of sickle hemoglobin.

We have investigated the effect of erythrocyte membrane preparations on the rate of polymerization and the solubility of deoxyhemoglobin S. The kinetics of polymerization was monitored by measuring changes in turbidity of hemoglobin S solutions as a function of time in a temperature-controlled cuvette. The solubility of deoxyhemoglobin S, an equilibrium measurement, was determined by measuring the hemoglobin concentration of the supernatant following centrifugation of the polymerized hemoglobin S solution. The solubility of deoxyhemoglobin S was unaffected by the presence of red cell membrane ghosts, inside-out red cell vesicles, or inside-out vesicles enriched in erythrocyte spectrin and actin (Bands 1, 2, and 5) in the hemoglobin solution. Furthermore, inside-out vesicles had no significant effect on kinetics of polymerization. The addition of erythrocyte membrane ghosts to the hemoglobin solution, in ratios approximating that of the intact red cell, increased the rate of polymerization up to 8-fold. However, when corrections were made for the excluded volume contributed by the membrane ghosts, the enhancement of the rate of polymerization was reduced to less than 3-fold. These results fail to show significant facilitation of intracellular sickling by nucleation sites on the red cell membrane.

Erythrocyte Membrane↗
PubMed1981

Anemic inpatients. Correlates of house officer performance.

To determine the correlates of the adequacy of the diagnostic evaluation of anemia, we conducted a prospective study on the medical services of a university-affiliated hospital. With the use of explicit criteria mapping techniques, the conditions of 204 (79%) anemic inpatients were adequately evaluated. By multiple regression analysis, the adequacy of evaluation showed significant correlations with the identity of the responsible house officer, the severity of the anemia, the patient's sex, and the service in which the patient received care. The performances of individual house officers were not significantly correlated with their subjective rankings by either their supervising residents or their attending faculty; however, a composite subjective ranking derived from the average of these two subjective rankings did correlate with objective performance in the anemia audit. We conclude that both patient and physician characteristics influence the adequacy of anemia evaluations and that objective audits may be a useful adjunct to the usual subjective methods for evaluating house officers' performances.

Anemia↗
PubMed1981

Nonenzymatic glycosylation of protein: relevance to diabetes.

Glucose can react nonenzymatically with proteins to form stable covalent linkages. The most abundant minor hemoglobin component in human red cells is hemoglobin AIc: glucose is attached to the N-terminal amino group of the beta chain by a ketoamine linkage. Hemoglobin AIc is increased two to three-fold in the red cells of diabetic patients. It is formed slowly and continuously throughout the 120-day lifespan of the red cell. Measurement of hemoglobin AIc provides an index of average blood glucose levels over the preceding two or three months. Thus, hemoglobin AIc has proved to be useful in assessing diabetic control and, perhaps, in screening people for diabetes. Many other proteins, such as lens crystallins, collagen and proteins in serum and in red cell membrane, are modified by nonenzymatic glycosylation. This structural alteration may lead to impaired protein function and, perhaps, contribute to the long-term complications of diabetes.

Blood Glucose↗
PubMed1981

Evolution of mammalian hemoglobin function.

Throughout their evolution, mammalian hemoglobins have acquired a broad repertoire of functional properties well suited to the internal milieu of the red cell. Mammals display a wide range in whole blood oxygen affinity dependent on three major factors: the intrinsic oxygen affinity of the hemoglobin, the level of red cell 2,3-DPG, and the response of the hemoglobin to 2,3-DPG. The concentration of 2,3-DPG varies among groups of mammals. Those animals (cats and ruminants) that have very low levels of this intracellular mediator have hemoglobins of intrinsically low oxygen affinity that fail to respond to the addition of 2,3-DPG. Mammals that have adapted to various types of hypoxia tend to have increased oxygen affinity, primarily mediated through reduced levels of red cell 2,3-DPG. In contrast, mammals who are experimentally subjected to low oxygen tensions develop decreased oxygen affinity owing to increased red cell 2,3-DPG. Mammals employ one of three different mechanisms for the maintenance of higher oxygen affinity of fetal red cells, compared to maternal red cells. Many of these phenomena can be satisfactorily explained at the molecular level but their adaptational significance is less clear.

Animals↗
PubMed1981

Modification of hemoglobin and other proteins by nonenzymatic glycosylation.

The most abundant minor hemoglobin component in human red cells is Hb AIc which is formed by the non-enzymatic condensation of glucose with the N-terminus of the beta-chain to form a stable ketoamine linkage. This adduct is increased in patients with diabetes mellitus and provides a useful index of diabetic control. In addition, glucose forms covalent attachments with lysine residues on both the alpha and beta chain, although these adducts are not readily separable by ordinary electrophoretic and chromatographic techniques. Additional minor hemoglobin components are formed by adducts with sugar phosphates. Nonenzymatic glycosylation also occurs on other proteins, particularly those with long turnover times and exposure to high concentrations of glucose. Examples include the proteins of the red cell membrane, albumin and lens crystallins. This phenomenon may be important in the pathogenesis of the long term control of diabetes.

Blood Glucose↗
PubMed1981

Subunit assembly of hemoglobins A and S.

It has been demonstrated that a difference in affinities of beta A and beta S chains for alpha chains exists. Furthermore, differential rates of dissociation of beta A and beta S chain tetramers have also been measured. It appears that the overall assembly of Hb A and Hb S, in vitro, can be governed by either the dissociation or combination reactions of its non-alpha-subunit.

Hemoglobin A↗
PubMed1980

A study of induced hyponatremia in the prevention and treatment of sickle-cell crisis.

Because the formation of sickle cells is dependent on the intracellular concentration of deoxyhemoglobin S, we investigated the possibility of altering or preventing sickle-cell crises by reducing serum sodium so as to cause red cells to swell. In three patients with sickle-cell anemia who had been disabled by recurrent painful crises, sustained dilutional hyponatremia was induced by 1-desamino-8-D-arginine vasopressin (DDAVP) in combination with a high fluid intake. Mean corpuscular hemoglobin concentration fell, and the degree of sickling at low partial oxygen pressure was reduced, as determined by morphologic criteria and by increased oxygen affinity of blood. Chronic hyponatremia (serum sodium, 120 to 125 mmol per liter) reduced the frequency of painful crises, whereas acutely induced hyponatremia abbreviated the duration of crises. These results, although preliminary, are encouraging enough to warrant further study of the safety and effectiveness of induced hyponatremia in the prevention and treatment of sickle-cell crises.

Adult↗
PubMed1980

Structural analysis of the minor human hemoglobin components: Hb AIa1, Hb AIa2 and Hb AIb.

Human hemolysate contains several minor hemoglobin components, including Hb AIa1, Hb AIa2, Hb AIb and Hb AIc which are post-translational modifications of the major component, Hb A0. Hb AIc is known to contain glucose attached to the N terminus of the beta chains by a ketoamine linkage. We separated the alpha and beta globin chains from purified Hb AIa1, Hb AIa2 and Hb AIb by ion-exchange chromatography. The beta chains were reducible by sodium borohydride and gave a positive thiobarbituric acid test. These results indicated that they are modified by ketoamine-linked carbohydrate. In addition, phosphate analysis revealed 1.5 phosphate residue associated with each beta AIa1 chain and 1 phosphate residue with each beta AIa2 chain. Hb AIa1, Hb AIa2 and Hb AIb were all found to be contaminated by non-globin proteins. Protein-sequencing approaches demonstrated that the N termini of beta AIa1, beta AIa2 and beta AIb were blocked. In support of this conclusion, analysis of tryptic digests of beta AIa2 and B AIb revealed modified N-terminal peptides. We conclude that, like Hb AIc, components Hb AIa1, Hb AIa2 and Hb AIb also contain a sugar moiety linked to the N terminus of the beta chain.

Amino Acid Sequence↗
PubMed1980

Nonenzymatic glycosylation of erythrocyte membrane proteins. Relevance to diabetes.

Nonenzymatic glycosylation of proteins of the erythrocyte membrane was determined by incubating erythrocyte ghosts with [3H]borohydride. The incorporation of tritium into protein provides a reliable assay of ketoamine linkages. The membrane proteins from 18 patients with diabetes incorporated twice as much radioactivity as membrane proteins from normal erythrocytes. After acid hydrolysis, amino acid analysis showed that the majority of radioactivity was localized to glucosyllysine. Autoradiograms showed that all of the major proteins of the erythrocyte membrane, separated by electrophoresis on sodium dodecyl sulfate gels, contained ketoamine linkages. No protein bands in either normal or diabetic erythrocytes showed significant preferential labeling. Erythrocyte membranes from three patients with hemolytic anemia showed reduced incorporation of tritium from [3H]-borohydride, indicating decreased nonenzymatic glycosylation. Two patients with diabetes and hemolytic anemia had incorporation of radioactivity similar to that of normal individuals. In these groups of patients the incorporation of tritium into erythrocyte membrane proteins correlated with levels of hemoglobin AIc. Thus the modification of membrane proteins like that of hemoglobin depends on blood glucose levels as well as erythrocyte age. These studies show that the enhanced nonenzymatic glycosylation of proteins in diabetics extends beyond hemoglobin to the proteins of the erythrocyte membrane and probably affects other proteins that have slow turnover and are exposed to high concentrations of glucose.

Anemia, Hemolytic↗