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Biomedical subjects

S Charache

Publications and source records attributed to S Charache.

At least 73 records · Page 4Linked to original sources
PubMed1985

Electronic blood cell counters. Faulty calibration due to type and amount of anticoagulant in collection tubes.

Electronic blood cell counters calibrated for mean corpuscular volume against normal venous blood collected in K3 EDTA (using a microhematocrit centrifuge) consistently yielded unacceptable data when used to assay commercial control materials. After recalibration using samples collected in Na2 EDTA acceptable results were obtained. Both types of sample tubes probably contained excess anticoagulant, and plasma was hypertonic in both. However, blood collected in Na2 EDTA had a lower pH, and the consequent swelling of RBCs due to a low pH compensated for osmotically induced shrinkage when microhematocrit values were measured.

Anticoagulants↗
PubMed1985

Pregnancy in carriers of high-affinity hemoglobins.

Pregnancy in female carriers of abnormal hemoglobins with great avidity for oxygen provides a unique opportunity to assess the importance of the usual difference in oxygen affinity between fetal and maternal blood. Outcome of pregnancy was recorded for carriers of hemoglobins Bethesda, Osler, and Yakima, whose p50s (9.5, 9.1, and 12 mm Hg at pH 7.4) were far lower than that of a normal fetus (23 mm Hg at pH 7.3). Neither spontaneous abortions nor intrauterine growth retardation could be attributed to the presence of high oxygen affinity in the mothers. In vitro simulations suggested that neither maternal or fetal polycythemia alone was sufficient to adjust for perturbation of the normal situation, and increased uterine and/or fetal blood flow probably provided additional compensation.

Adult↗
PubMed1985

Quantitative analysis of abnormal hemoglobins by agar gel electrophoresis.

Measurement of the proportion of abnormal hemoglobin in a hemolysate is essential for differentiation of simple and compound heterozygotes (e.g., sickle cell trait vs. sickle thalassemia), for differential of alpha- and beta-thalassemia in compound heterozygotes, and for differentiation of various types of beta-thalassemia in such persons. Utilization of such measurements is hampered by the imprecision and inconvenience of current methods. We have adapted a readily available agar electrophoresis method for this purpose, scanning unstained gels at 420 nm. The new method is particularly valuable for rapid estimation of percent of HbS after partial exchange transfusion in patients with sickle cell anemia. It cannot be used for quantitation of HbF or for quantitation of hemoglobins that comigrate with HbA; contrariwise, it can be used for hemoglobins that only separate from HbA on agar (e.g., HbBethesda).

Anemia, Sickle Cell↗
PubMed1984

beta-Thalassemia in American Blacks: novel mutations in the "TATA" box and an acceptor splice site.

beta-Thalassemia genes, although often mild in their effects, are common among American Blacks. We have begun a systematic molecular analysis of beta-thalassemia mutations in this group. DNA polymorphisms in the beta-globin gene cluster were examined among 22 beta-thalassemia chromosomes. Six different haplotypes were observed. beta-globin genes of two of these were cloned, and their phenotypes were examined both in heterologous cells upon transient expression and in vivo. The gene found in the most common haplotype (9 of 22 chromosomes) contained a single base substitution (A----G) at position -29 within the highly conserved proximal promoter element (the "TATA" box). This mutant gene directed beta-globin RNA at 25% of normal levels both in heterologous cells and in vivo. It was associated with a mild beta +-thalassemia phenotype. A different gene, isolated from an apparently rare haplotype (1 of 22 chromosomes), had a single base substitution (A----G) within the acceptor splice site of the second intervening sequence. This mutation abolished normal RNA splicing so that the only RNA made from the gene in vitro was an alternatively spliced RNA, which could not encode beta-globin. The mild deficit in beta-globin production attributable to the -29 A----G mutant allele most likely accounts for the frequently mild nature of beta-thalassemia among American Blacks.

Adolescent↗
PubMed1983

Treatment of acute sickle cell crises with a vasopressin analogue.

Eight patients with sickle cell anemia were treated for acute painful crises with DDAVP and intravenous fluids; five were treated with placebo and the same regimen of fluid administration. Although hyponatremia was produced in both treatment groups, duration of hospitalization did not differ between them, nor did it differ from concurrent hospitalization of other patients who received conventional treatment. Safe induction of hyponatremia required intensive laboratory surveillance, and serum sodium could be lowered without use of DDAVP. These data suggest that a controlled trial hyponatremia for acute sickle cell crises should not be performed.

Acute Disease↗
PubMed1983

Effects of blood transfusion on exercise capacity in patients with sickle-cell anemia.

Although sickle cells have increased intracellular viscosity, the viscosity of patient's blood is usually not increased, because of the low hematocrit typically found in such patients. When patients receive transfusions, their exercise capacity increases, but it is unclear whether the change is due primarily to increased hemoglobin concentration, or also reflects improved flow properties of the blood due to dilution of sickle cells with normal erythrocytes. To evaluate the relative importance of these two factors, submaximal exercise studies were performed before and after a series of transfusions. Exercise capacity improved and the patients were able to perform increased amounts of work at lower heart rates. Regression analyses indicated that the percent of sickle cells in patient's blood did not have a significant effect on exercise capacity after the transfusion-induced increase in hemoglobin concentration was taken into account. At the hematocrits typically found in patients, altered viscosity of blood due to the presence of sickle cells is much less important than hemoglobin concentration as a determinant of exercise capacity.

Adolescent↗
PubMed1983

Treatment of sickle cell anemia with 5-azacytidine results in increased fetal hemoglobin production and is associated with nonrandom hypomethylation of DNA around the gamma-delta-beta-globin gene complex.

Increased production of fetal hemoglobin (HbF) was observed in a patient with sickle cell anemia treated with 5-azacytidine. Each of four courses of therapy resulted in a rapid and prolonged increase in the percentage of HbF containing reticulocytes (F reticulocytes) and HbF containing erythrocytes (F cells). The percentage of HbF in peripheral blood rose from 1.8 to 8.9%. The rise in HbF production was accompanied by an increase in peripheral blood hemoglobin concentration from 8 to 12 g/dl and an increase in mean erythrocyte volume. Treatment with 5-azacytidine resulted in hypomethylation of total genomic and a Y-chromosome-specific DNA fragment isolated from both peripheral blood and bone marrow. Of 15 restriction enzyme sites around the gamma-delta-beta-globin gene complex, only 2 became hypomethylated: one 107 bases 5' to the gamma G and the other 107 bases 5' to the gamma A globin genes.

Adult↗
PubMed1983

Differences in the reaction sequences associated with drug-induced oxidation of hemoglobins E, S, A, and F.

Comparisons were made of drug-induced oxidation of purified hemoglobins A, S, E, and F. Repetitive spectral scans of reaction mixtures containing menadione showed that Hb E was the most reactive and Hb F was the least reactive of the hemoglobins studied. Hb E oxidation was only slightly faster than normal, but it produced much larger relative quantities of low-spin ferric hemoglobin (hemichromes). Hb F oxidation was considerably slower than normal but produced normal amounts of hemichromes relative to methemoglobin. Precipitation occurred in the order E greater than S greater than A greater than F. The abnormally slow rate of Hb F oxidation was even more striking when the oxidant was acetylphenylhydrazine (APH), and the sensitivity of the reaction to catalase was severely diminished. These hemoglobins thus exhibit entirely different reaction profiles during drug-induced oxidation. The amino acid substitution in Hb E alters the globin tertiary structure, so that hemichromes can more readily form, whereas the decreased susceptibility to oxidative denaturation of Hb F appears related to the absence of a site that normally reacts with hydrogen peroxide to increase oxidation rate. Such Hb F stability is consistent with the mild phenotypic expression of doubly heterozygous beta-thalassemia/HPFH and Hb S/HPFH. The role of Hb E instability in altered red cell morphology relative to the thalassemia-like deficit of beta globin mRNA has not been entirely resolved. Nevertheless, the clinical repercussions of the abnormal properties of Hb E are mild, and they may be involved with the prevalence of this hemoglobin in Southeast Asia as a balanced polymorphism in which the advantage to heterozygotes is, as yet, unclear.

Adult↗
PubMed1982

Comparison of the effects of lower monohydric alcohols and inositol hexaphosphate on the oxidation of hemoglobin by menadione.

Analyses of optical absorption spectra show that the lower monohydric alcohols (methanol, ethanol, 1- and 2-propanol and 1-butanol) exert two distinct effects upon the oxidation of oxyhemoglobin by menadione. As chain length increases from one to three carbons, the rate of oxidation decreases. In contrast, as chain length increases, hemichrome production is enhanced along with the tendency for the oxidized hemoglobin to precipitate. Inositol hexaphosphate, which shifts the hemoglobin-oxygen dissociation curve far to the right, also increases the rate of oxidation. However, the ability of methanol and ethanol to alter oxidation rates is greater than that of IHP, and does nor correlate with their effect on oxygen affinity. The effect of these alcohols on rate of oxidation appears related primarily to their capacity for direct binding to the ferric iron-heme complex as it forms. Increased hemichrome formation, in higher alcohols, and subsequent precipitation, is primarily a solvent effect associated with increasing hydrophobicity. Menadione-induced oxidation may require deoxyhemoglobin in the presence of a small amount of oxygen in order to proceed.

Alcohols↗
PubMed1982

Drug-induced oxidation and precipitation of hemoglobins A, S and C.

Analysis of optical absorption spectra of drug-hemoglobin reaction mixtures show that oxidation of oxyhemoglobins A, S and C by menadione and acetylphenylhydrazine and the consequent formation of methemoglobin, hemichromes and 'choleglobin' proceed at identical rates for all three hemoglobins. Nevertheless, precipitate formation, which is linked to hemichrome production, occurs in a definite order: S greater than C greater than A. Differences in precipitability among these three hemoglobins are linked to an as yet unidentified property of the aggregate hemichromes, which is not directly related to the rate of total hemichrome production.

Chemical Precipitation↗
PubMed1982

Hemoglobin H disease and multiple congenital anomalies in a child of northern European origin.

Hemoglobin H (HbH) disease was recently described in three unrelated northern European boys with mental retardation. We have studied a somewhat similar patient, in whom HbH disease was associated with multiple congenital anomalies. Restriction endonuclease analysis of DNA from this proband yielded a pattern consistent with the alpha-/-- genotype commonly associated with the HbH phenotype in Asians. His parents both carry alpha thalassemia, in contrast to the previously described families in which only one of the two parents was a carrier.

Abnormalities, Multiple↗
PubMed1982

Homozygous alpha thalassemia/Hb G Philadelphia.

Microcytic red cells from a 70 year old Negro man with mild anemia contained only hemoglobin G-Philadelphia. Red cells from all of his children had low-normal MCV's, and contained 32-34 percent of the abnormal hemoglobin. Oxygen affinity of his blood and stability of his hemolysate were normal, suggesting that his mild anemia was not caused by the the abnormal hemoglobin. Restriction endonuclease analyses of DNA from the proband and his offspring showed that the alpha G-Philadelphia globin gene exists in only one copy per chromosome. The new gene was probably created by an unequal cross-over which deleted an alpha globin coding sequence (derived from one or both alpha globin genes), as well as some or all of the DNA sequence between those genes.

Aged↗
PubMed1982

Increased blood viscosity in a patient with sickle cell anemia.

Although intracellular viscosity is greatly increased in deoxygenated sickle cells, the viscosity of blood is not, because patients' packed cell volumes (PCV) are usually extremely low (15-25%). A young women with sickle cell anemia was admitted with a typical painful crisis, and was found to have a PCV of 39% with a reticulocyte count of 3.6%. During a hospitalization of 48 h, the PCV rose to 46%; her pain subsided but her behavior became bizarre, cardiopulmonary arrest occurred, and she could not be resuscitated. At autopsy, no abnormalities were found except for congested blood vessels containing sickle cells. It was subsequently discovered that she and her family had been exposed to carbon monoxide for a week prior to admission. Blood samples from another patient studied with a PCV of 40% showed progressively decreased viscosity if they contained 13-20% carboxyhemoglobin. It is suggested that preexisting accelerated erythropoesis was further stimulated by CO, and caused "compensatory polycythemia", but that the CO prevented most of the newly formed cells from sickling and being destroyed. Admission to hospital caused a gradual disappearance of CO but the patient's PXV continued to rise. Her death may have been due to a rare form of hyperviscosity syndrome, when the level of carboxyhemoglobin in her blood fell to more normal levels and her cells regained the ability to sickle. Treatment of sickle cell anemia with an effective non-covalently bound agent could have a similar effect, if the agent were withdrawn abruptly.

Acute Disease↗