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Query: UMLS:C0002895 (sickle cell disease)
 11,747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report the clinical, hematological, and molecular findings observed in 32 Sicilian patients with sickle cell disease. None of our patients received regular blood transfusions and careful infectious disease prophylaxis was carried out for all. Haplotyping of beta S chromosomes was performed in all patients; all were homozygous for haplotype #19 (Benin). Gene mapping excluded the presence of an alpha-thalassemia in 13 of our patients; none of the relatives showed any evidence of the presence of alpha-thalassemia. Hb F levels were 11.8 +/- 5.9% with G gamma representing 39.6 +/- 3.6% of total gamma chain. Hb F levels were higher in females than in males (12.5 +/- 5.9% versus 9.7 +/- 6.5%) but the difference was not statistically significant. All patients, regardless of age and sex, were anemic with normal mean corpuscular hemoglobin concentration, high mean corpuscular volume and mean corpuscular hemoglobin, and mild reticulocytosis. Analysis of clinical manifestations suggests that our patients have a disease of moderate severity.
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PMID:Clinical, hematological, and molecular features in Sicilians with sickle cell disease. 148 18

Hb Mizuho, an unstable beta chain variant with a Leu----Pro substitution at position beta 68, was observed in a young Caucasian boy from Kentucky. Identification was made by sequence analyses of amplified DNA and by hybridization of amplified DNA with specific probes. The patient had high Hb F levels up to the present age of nearly 5 years; this high Hb F might in part be responsible for his condition which was considerably milder than that seen in the two patients described in earlier reports. The increased gamma chain synthesis may be due to special characteristics of the beta-globin gene cistron which are comparable to those observed in sickle cell anemia patients with a relatively mild disease.
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PMID:Hb Mizuho or alpha 2 beta (2)68(E12)Leu----Pro in a Caucasian boy with high levels of Hb F; identification by sequencing of amplified DNA. 172 94

Hematological and hemoglobin composition data are presented for seven Arabian SS patients with mild disease and with high Hb F levels varying between 21 and 34%. Four patients were homozygous for a beta S chromosome with a specific haplotype (#31). The data for these four patients were similar to those for three other SS patients (and for five patients reported earlier, Ref. 2) who were heterozygous for the same beta S chromosome (#31) and for a beta S chromosome with another haplotype (mainly #19). These data offer additional evidence indicating that the increased gamma chain production is specific for the beta S chromosome with haplotype #31. The similarities in hematological data and Hb F levels between these two groups of SS patients and the normal Hb F value in Hb S heterozygotes with beta S chromosome (#31) support the suggestion that the increased Hb F production mainly occurs in response to the anemia of the sickle cell disease.
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PMID:Hematological observations on Arabian SS patients with a homozygosity or heterozygosity for a beta S chromosome with haplotype #31. 241 79

High-performance liquid chromatographic procedures have been used in the detection and identification of a new gamma chain of human fetal hemoglobin (Hb). This M gamma chain is characterized by a Leu----Met replacement at position gamma 141; no other structural variations have been observed. The M gamma chain has been detected in red cell lysates of subjects with a heterozygosity for one of many types of so-called hereditary persistence of fetal hemoglobin conditions, which are characterized by an increased level of Hb F in adult life, in sickle cell anemia, and in a few cord blood samples. At present it is not possible to definitely identify the genetic cause of this newly discovered heterogeneity; an infidelity in translation or the existence of an unrecognized gamma globin gene should be considered.
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PMID:The M gamma chain of human fetal hemoglobin; its identification and occurrence. 243 48

An increased synthesis of fetal hemoglobin in adult life is a common feature of the genetically determined severe disorders like beta thalassemia and sickle cell anemia. A continued synthesis of fetal hemoglobin in adults is also characteristic of clinical or subclinical syndromes like respectively delta beta thalassemia or hereditary persistence of fetal hemoglobin (HPFH). These disorders are highly heterogeneous with respect to their molecular defects as well as to the composition of Hb F. We report here a novel case of hereditary persistence of fetal hemoglobin in heterozygous state discovered by chance, in a young perfectly healthy french man. The gamma chain of his fetal hemoglobin was almost entirely composed of G gamma chains. Molecular analysis of the DNA revealed the existence of triplicated gamma genes on one chromosome with the genotype arrangement of G gamma-G gamma-A gamma. A polymorphic Xmn I restriction site (at position -158 5' to the cap site) was present in 5' of both of these G gamma genes. The presence of this site in front of G gamma gene had previously been shown to be associated both with high G gamma phenotype constitutively and also with high fetal hemoglobin level only in case of anemic stress. In the absence of any anemic stress in this individual, the constitutive increase of both fetal hemoglobin and G gamma chains could be due to the presence of a chromosome with triplicated arrangement of gamma genes. The classical triplication (G gamma-A gamma-G gamma-A gamma) does not result in HPFH phenotype.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Analysis of the recombination zone in hereditary persistence of fetal hemoglobin with fetal gene rearrangement of the G gamma-G gamma-A gamma type]. 244 55

A new gamma chain of human fetal hemoglobin, the M gamma chain, has been detected by high performance liquid chromatography (HPLC). It is characterized by a Leu----Met replacement at position gamma 141; no other structural variations have been found. The M gamma chain has been observed in red cell lysates of subjects with a heterozygosity for one of many types of hereditary persistence of fetal hemoglobin (HPFH), in sickle cell anemia, and in a few cord blood samples. At present, the genetic cause of this newly discovered heterogeneity is not known; an infidelity in translation or the existence of an unrecognized gamma globin gene should be considered.
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PMID:The M gamma chain of human fetal hemoglobin. 244 16

High-performance liquid chromatography (HPLC) has been successfully used in the quantitation of the relatively minute amounts of hemoglobin types recovered from in vitro cultures of hemoglobin-synthesizing erythroid progenitor (BFU-E) cells. This reversed-phase HPLC method uses the Vydac C4 column and water-acetonitrile-trifluoroacetic acid as mobile phases; it has been applied to the study of fetal hemoglobin synthesis patterns in ten homozygous sickle cell anemia patients and a similar number of their heterozygous relatives along with a few normal control subjects. A significant increase in the total gamma chain level was observed in the BFU-E lysate samples corresponding to the whole blood lysates of all the patients and their heterozygous relatives, except in one patient with the beta S haplotype Mor. On the other hand, the relative level of the G gamma chains appeared to be decreased in the BFU-E lysate samples of all except the individuals carrying the Mor haplotype, where it is reversed. The method has considerable advantages over other chromatographic and electrophoretic procedures; it is extremely sensitive and allows quantitation of all different globin chains in one single chromatogram.
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PMID:Application of high-performance liquid chromatographic methodology to the analysis of hemoglobins synthesized in erythroid progenitor cells. 248 Mar 57

A newly developed HPLC procedure (1) was used to study the percentages of G gamma and A gamma chains in the Hb F from newborn and patients with sickle cell anemia. The method gives data comparable to those obtained with a more laborious chemical procedure. However, the presence of the A gamma T chain, i.e., the A gamma chain with an Ile replaced by Thr substitution at position 75, interferes with the determination of the G gamma to A gamma ratio because the A gamma T and G gamma chains have the same chromatographic mobility.
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PMID:The determination of the percentages of G gamma and A gamma chains in human fetal hemoglobin by HPLC. 615 3

Fetal haemoglobin (Hb F) synthesis has been studied in 22 cases of sickle cell anemia (SS) from Saudi Arabia and compared with an equal number of cases of African origin. Among the Saudi Arabs gamma chain synthesis ranged from 4.0% to 19.9% of the total non-alpha chain synthesis (mean 8.1%) while the corresponding range for the Negro cases was < 0.3% to 4.6% (mean 1.7%). In both groups the peripheral blood Hb F level was on average 3--4 times higher than the proportion synthesized, indicating that the selective survival of Hb F containing cells (F cells) was an important factor in determining the final Hb F levels. Among the Saudi Arab cases there was a significant negative correlation between the degree of F cell enrichment and either the Hb F level of the percentage gamma chain synthesis. No such correlation was observed among the Negro cases. A high proportion of the cases in both groups were carriers of alpha thalassaemia in addition to SS, but no effect of alpha thalassaemia on Hb F production was observed.
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PMID:Hb F synthesis in sickle cell anaemia: a comparison of Saudi Arab cases with those of African origin. 615 84

A modification of a high pressure liquid chromatographic (HPLC) procedure is described that enables the complete separation and quantitation of the A gamma T, A gamma I, and G gamma chains in human fetal hemoglobin. The method, which is fast and accurate, requires 5 to 2000 micrograms Hb F. The purity of the Hb F is not essential and admixture of up to 70% adult Hb does not interfere with the determination. The method has been applied to the Hb F of 64 Black SS patients and 7 persons with the Hb S-HPFH (G gamma A gamma type) conditions. (A) Both "adult" G gamma to A gamma (2:3) and "newborn" G gamma to A gamma (3:2) ratios were observed in adult SS patients, 8 yr and older. Only 12% of the SS patients had the "newborn" ratio. This high G gamma to A gamma ratio may be due to a modification of the genetic switch mechanism that regulates the change of this ratio after birth. (B) Intermediate G gamma to A gamma ratios were only found in young SS patients, 5 yr of age or less. The results suggest a delayed switch of the newborn leads to adult ratio in sickle cell anemia. (C) The A gamma T chain was present in only 6% of all SS patients. One patient is homozygous for this variant chain. (D) Three of the 7 subjects with Hb S-HPFH were positive for the A gamma T chain. Its percentage was low, which suggests that the A gamma T chain gene is in trans of the HPFH determinant. (E) Quantitation of the three gamma chain types is also possible in the Hb F from Hb S heterozygotes with (nearly) normal Hb F levels. Such an analysis is useful for an evaluation of genetic conditions involving variations in the production of (different types of) Hb F.
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PMID:Quantitation of three types of gamma chain of HbF by high pressure liquid chromatography; application of this method to the HbF of patients with sickle cell anemia or the S-HPFH condition. 616 Aug 89


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