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Biomedical subjects

S Charache

Publications and source records attributed to S Charache.

At least 91 records · Page 5Linked to original sources
PubMed1982

Treatment of patients with sickle cell anemia--another view.

Sickle cell anemia is a bad disease, and it occurs in black patients who still face obstacles that whites don't appreciate. Even if a new cure burst forth, it would not be available to many patients, and others would be afraid of it. It probably would not be as safe or effective as chloroquine for malaria or penicillin for pneumonia--and as a result, we should try to improve our present means for delivering care. Treatable complications must be recognized, and painful episodes must be managed with knowledge that no type of pain is exclusively physical or mental. If patients are to function in society, they must have marketable skills--and the current educational system in the United States is not prepared to provide such skills to such difficult students. Finally, there will be some lost souls, hopeless patients who live a shadowy life from which rescue seems nearly impossible. They need specialized care which is not currently available. Such care in special protected environments could be cost-effective, but would require such prolonged enthusiasm and commitment that it may be impossible to achieve.

Anemia, Sickle Cell↗
PubMed1981

Variability of oxygen affinity of blood: human subjects native to high altitude.

Whole blood O2 equilibrium curves (OEC) were measured in 46 Peruvians native to high altitude (4,540 m) and in 25 sea-level controls. A method was employed that records the entire OEC from 0 to 150 Torr with constant pH and PCO2. The data were analyzed by fitting the Adair equation describing the successive oxygenation of hemoglobin. At pH 7.4 the PO2 at which hemoglobin is half-saturated with O2 (P50) was significantly higher in the high-altitude population (31.2 +/- 1.9 Torr) than in controls (29.2 +/- 1.8 Torr, P less than 0.001). The acid-base status of the high-altitude subjects, however, was that of compensated respiratory alkalosis (plasma pH 7.439 +/- 0.065), and when the P50's were corrected to the subjects' plasma pH the values (30.1 +/- 2.2 Torr) could no longer be distinguished from the controls. We conclude that, on the average, increased P50 resulting from increased red cell 2,3-diphosphyoglycerate concentration at high altitude is offset by compensated respiratory alkalosis with the net result that the position of the OEC more closely approaches that of sea-level humans than has hitherto been thought. Considerable variation exists in P50, both at sea level and high altitude. This variation might have important consequences for acclimatization and survival under adverse environmental conditions.

2,3-Diphosphoglycerate↗
PubMed1981

The molecular basis of hemoglobin Grady.

DNA from individuals heterozygous for the extended alpha-chain variant Hb Grady were studied by gene counting and restriction enzyme analysis. Neither method indicated the presence of an extra (fifth) alpha gene, which argues that if this variant arose by unequal crossing over, the event most likely involved mispairing between alleles rather than between the separate alpha 1 and alpha 2 loci.

Chromosome Mapping↗
PubMed1981

Failure of desmopressin to lower serum sodium or prevent crisis in patients with sickle cell anemia.

An analogue of arginine vasopressin (desmopressin, DDAVP) was evaluated for production chronic hyponatremia and prevention of sickle cell crisis. With sodium restriction (100 meq Na + / day) and water loading ( greater than 3 liters/day), persistent hyponatremia could not be achieved, nor could crises be prevented or aborted. Patients would not comply with a regimen of lower salt and higher fluid intake. More rigorous treatment might be practical during acute sickle cell crises, and a regimen similar to that used here might be more effective in children, whose renal concentrating mechanisms are still intact.

Adult↗
PubMed1980

Oxygen affinity and stability of hemoglobin Dunn alpha 6(A4)Asp replaced by Asn): use of isoelectric focusing in recognition of a new abnormal hemoglobin.

A new slow-moving hemoglobin was found in low proportion in an asymptomatic black woman. Isoelectric focusing helped to distinguish it from other hemoglobins with similar electrophoretic mobility, and amino acid analysis showed that aspartic acid alpha 6 (A4) had been replaced by asparagine. Oxygen affinity was increased, but the Bohr and DPG effects were normal. Stability of the purified hemoglobin was decreased, but that of hemolysates was normal. Abnormal oxygen affinity of this variant, and that of hemoglobin Sawara (alpha 6(A4)Asp replaced by Ala), may reflect loss of a salt bridge between Asp alpha 6 and Lys-alpha 127(H10) which would tend to favor the high-affinity R conformation of the molecule.

Adult↗
PubMed1980

Management of sickle cell disease in pregnant patients.

Data from a total of 74 pregnancies in 42 patients with sickling disorders seen at Johns Hopkins Hospital are compared with similar data from other centers. Although risks are still higher than those for women without sickle cell disease, they have diminished significantly from those reported earlier. Prophylactic transfusion therapy may decrease these risks further, but benefits of transfusion are unproved at present. Patients with sickling disorders should receive meticulous individualized treatment until further data are made available.

Anemia, Sickle Cell↗
PubMed1979

Conformation in solution of hemoglobin Osler (alpha 2 A beta 2 145 Tyr replaced by Asp).

Computer simulations of Gelin and Karplus ((1977) Proc. Natl. Acad. Sci. U.S.A. 74, 801-805) suggest that in hemoglobin upon ligation the penultimate tyrosyl residues of the subunits are not expelled from the hydrophobic pockets described in the crystals between the helices E and F (Perutz, M.F. (1970) Nature 228, 726-737). This implies that both the liganded and unliganded conformations of hemoglobin may be affected by mutations involving such residues. Investigation of the conformational behavior of liganded and unliganded hemoglobin Osler was conducted measuring the functional properties, the subunits dissociation, the CD and electronic spectra, the protons absorption upon interaction with polyanions, and the reactivity of the -SH groups of the protein. The results suggest that both the liganded and unliganded conformations of the system are affected by the mutation, confirming the anticipations of Gelin and Karplus on the relevance of tyrosine at beta 145 for both allosteric states of hemoglobin.

Alkylation↗
PubMed1979

Comparison of microchromatography and electrophoresis with elution for hemoglobin A2 (Hb A2) quantitation.

Microcolumns prepared in the authors' laboratory, two commercial microchromatography kits, and electrophoresis with elution were compared for Hb A2 quantitation. Day-to-day imprecision of microchromatographic methods was similar (CV 4.7--6.6%) and somewhat less than electrophoresis with elution (CV 8.0--9.1%). Both commercial kits showed variable imprecision in different lots; one lot of Kit B gave erratic results due to resin leakage. From 49 patient specimens, Kit A microcolumns and those of the authors identified the same 14 patients with an elevated percentage of Hb A2 and showed good correlation (P = 0.90), although Kit A showed constant bias toward higher values. Electrophoresis with elution resulted in a false-positive and a false-negative value, did not correlate well with microcolumns (P = 0.78 and 0.76), and showed proportional bias toward lower values for an elevated percentage of Hb A2. Commercial kits were convenient, relatively quick, and cost-effective. Frozen, stabilized hemolysates performed well for quality control.

Blood Protein Electrophoresis↗
PubMed1979

The effect of hemoglobin F-Chesapeake (alpha 2 92 Arg. leads to Leu gamma 2) on fetal oxygen affinity and erythropoiesis.

A carrier of hemoglobin Chesapeake, born of a normal mother, had a cord-blood hematocrit of 60%. The oxygen affinity of his blood was increased. Hemoglobin F-Chesapeake (alpha 2 Ches gamma 2), partially purified from the infant's blood, had oxygen affinity greater than that of hemoglobin A, but less than that of the adult form of the abnormal hemoglobin (alpha 2 Ches beta 2). These findings suggest that the conformation of that part of the gamma chain which contacts the site of amino acid substitution in Hb F-Chesapeake is similar to the analogous region of hemoglobin F. They also support the hypothesis that regulation of erythropoiesis in late fetal life is similar to that of the adult, and is under fetal control.

Erythropoiesis↗
PubMed1979

"Acute chest syndrome" in adults with sickle cell anemia. Microbiology, treatment, and prevention.

Fifty-two episodes of fever, chest pain, increased leukocytosis, and pulmonary infiltrate ("acute chest syndrome") were studied in 28 adults with sickle cell anemia. Possible bacterial pathogens were identified in sputum cultures from less than half of the episodes; no pneumococci were found, and Staphylocococcus aureus was the only bacterium associated with a longer illness than that seen when only normal flora were recovered. Much disease diagnosed as "pneumonia" in adults with sickle cell anemia is probably pulmonary infarction. Many of these patients will recover with no more than modest supportive care; if antibiotics are used they should be directed against S aureus (and possibly Hemophilus species). Pneumococcal polysaccharide vaccine has great potential for preventing life-threatening infection in children with sickle cell anemia, but may not change the incidence or severity of the acute chest syndrome in adults.

Acute Disease↗
PubMed1979

Oxygen transport in a woman with hemoglobin Hope/beta+ thalassemia.

Because their blood may "unload" oxygen more readily than normal, people with hemoglobin of low oxygen affinity might be expected to be anemic. We have studied a woman with hemoglobin Hope/beta+ thalassemia, whose hemoglobin level was 10.4 to 12.3 gm/dl (normal 14 +/- 2) despite a P50 of 41 mm Hg (normal 26). Her cardiac index was normal, yielding a calculated mixed venous PO2 of 51 mm Hg (normal 34 to 49). Oxygen transport in patients with low oxygen affinity can be maintained by a variety of homeostatic responses, only one of which is altered erythropoiesis.

Adult↗
PubMed1978

Individual variation in the production and survival of F cells in sickle-cell disease.

The protective role and underlying sources of the elevated levels of fetal hemoglobin associated with sickle-cell anemia were reassessed by microscopical immunodiffusion assays. Three variables that contribute to levels of fetal hemoglobin were examined: the percentage of fetal-hemoglobin-containing reticulocytes produced; the quantity of fetal hemoglobin synthesized within such cells; and the extent to which the fraction of fetal-hemoglobin-bearing erythrocytes is enriched beyond the level produced. Four general findings emerged from analysis of 29 patients: each variable is separately regulated; the expression of each is often distinctly different between individual patients; contrary to prior speculation, production of fetal hemoglobin may be as great in the absence of heterocellular hereditary persistence of the hemoglobin as in its presence; and fetal hemoglobin does not, as often supposed, guarantee preferential cell survival. We conclude that the differences encountered among patients must reflect heterogeneity among factors that modify production and survival of cells bearing fetal hemoglobin.

Adult↗
PubMed1978

The structure of hemoglobin Hopkins-2.

Hemoglobin Hopkins-2 was originally reported to contain two abnormal alpha chains. Both had aspartic acid instead of the normal histidine at position alpha 112; the second alpha chain also contained two additional amino acid substitutions. In subsequent reports of the structure of this hemoglobin, only the His replaced by Asp substitution was found. To determine whether the second abnormal alpha chain was limited to the original kindred, the structure of their hemoglobin was redetermined. Only the His replaced by Asp substitution was present.

Aspartic Acid↗
PubMed1978

Sickle cell anemia.

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Anemia, Sickle Cell↗
PubMed1978

Hb Potomac (101 Glu replaced by Asp): speculations on placental oxygen transport in carriers of high-affinity hemoglobins.

Blood from a woman with unexplained erythrocytosis had increased oxygen affinity, but no abnormality could be detected by electrophoresis or chromatography of her hemolysate. Separation of the tryptic peptides of her beta chains disclosed two half-sized peaks in the regions of beta T-11. The faster of these was abnormal, with the structure beta 101 Glu replaced by Asp. The new hemoglobin was called "Potomac." Three of the proband's four surviving siblings and both of her children were carriers. Differences in the ratio of carrier: normal children born to male of female carriers of 23 other high-affinity hemoglobins were not significant. The high proportion of carriers in this kindred was probably due to chance alone, and not because high maternal oxygen affinity interfered with oxygen transport to fetuses with normal hemoglobin.

Adult↗
PubMed1978

Variability of the homeostatic response to altered p50.

Blood from carriers of hemoglobin Osler (Hb Osler) had almost the same oxygen affinity as that of carriers of Hb McKees Rocks (Hb MR) (P50 10-11 mm Hg), but Hb concentrations were higher in male carriers of the former (21.6 versus 17.2 g/dl). Two carriers of each Hb were studied to compare their adaptations to altered oxygen affinity and their responses to phlebotomy. All four were healthy, and all excreted normal amounts of erythropoietin. Carriers of Hb MR had somewhat lower mixed venous pO2 than carriers of Hb Osler. There was no suggestion that phlebotomy impaired ability to exercise in either group of patients.

Adolescent↗