PubMed Health⌕ Search

Biomedical subjects

D Labie

Publications and source records attributed to D Labie.

At least 109 records · Page 6Linked to original sources
PubMed1983

Alpha-globin loci in homozygous beta-thalassemia intermedia.

Homozygous beta-thalassemia intermediate (TI) differs from thalassemia major (TM) in being less severe clinically. Associated alpha-thalassemia could account for the TI phenotype by reducing the alpha/non-alpha chain imbalance. We have analyzed the alpha loci of 9 TI and 11 TM patients by restriction endonuclease mapping. All the TM and 7 of the TI patients have the normal complement of four alpha-globin genes (alpha alpha/alpha alpha). One TI patient has three alpha-globin genes (alpha alpha/-alpha), and another TI patient has five alpha genes (alpha alpha/alpha alpha alpha).

Adolescent↗
PubMed1983

Four new haplotypes observed in Algerian beta-thalassemia patients.

beta-Thalassemia, a heterogeneous group of human anemias affecting the expression of beta-globin, is caused by a number of molecular defects. Restriction endonuclease mapping of ethnic populations has revealed many polymorphisms within and around the beta-like globin genes, combinations of which are assigned as haplotypes. Several haplotypes appear to be strongly linked with the molecular defects causing thalassemia in Greek and Italian patients (Orkin et al. 1982). We describe here haplotypes from 40 Algerian beta-thalassemic patients and eight normals determined by restriction endonuclease mapping at seven polymorphic sites. Four haplotypes previously unreported were observed in these thalassemic patients; this argues the existence in this population of undescribed beta-thalassemia alleles. The knowledge of the haplotypes in thalassemic families could be used for prenatal diagnosis of homozygote forms.

Algeria↗
PubMed1983

Influence of thyroid status on hemoglobin A2 expression.

We studied the electrophoretic pattern of hemoglobin (Hb) and red blood cell indices in 128 women divided into four groups: group I, 36 nonanemic hyperthyroid women, divided in two subgroups: 36 with untreated hyperthyroidism (subgroup IA) and 9 made euthyroid by antithyroid drug therapy (subgroup IB); group II, 12 nonanemic women with untreated hypothyroidism; group III, 30 women known to be heterozygous for beta-thalassemia; and group IV, 50 healthy women. The mean (+/- SEM) HbA2 level was higher (P less than 0.001) in subgroup IA (3.21 +/- 0.06%) than in subgroup IB (2.42 +/- 0.09%) and group IV (2.48 +/- 0.04%), but lower (P less than 0.001) than in group III (5.26 +/- 0.12%). The mean HbA2 level was lower (P less than 0.001) in group II (1.99 +/- 0.08%) than in group IV. Hb fetal was detectable in eight patients of subgroup IA and undetectable in subgroup IB and groups II and IV. The mean cellular volume was lower (P less than 0.001) in subgroup IA than in other nonanemic groups. The mean cellular volume was higher (P less than 0.001) in group II than in group IV. Follow-up of nine patients who became euthyroid with treatment showed the normalization of these erythrocyte parameters. These results suggest that thyroid hormones can modulate the synthesis of delta- and gamma-globin chains.

Adult↗
PubMed1983

Hemoglobin Maputo: a new beta-chain variant (alpha 2 beta 2 47 (CD6) Asp replaced by Tyr) in combination with hemoglobin S, identified by high performance liquid chromatography (HPLC).

During a routine hematological investigation, a slowly-moving hemoglobin variant was detected in a 2-year-old child from Maputo (Mozambique) in combination with hemoglobin S. Structural studies carried out by HPLC demonstrated a previously unreported amino acid substitution, beta 47 (CD6) Asp replaced by Tyr. The new hemoglobin variant has been named hemoglobin Maputo.

Amino Acid Sequence↗
PubMed1983

Alpha-thalassemia is related to prolonged survival in sickle cell anemia.

We have determined the frequency of deletional alpha-thalassemia in black populations in the USA and Africa that harbor sickle cell anemia. In normals, the frequency of the chromosome bearing a deletion of one of the two normal alpha gene loci, designated (-alpha), ranged from 0.12 to 0.16, and in sickle trait subjects, the frequency ranged from 0.18 to 0.20. By contrast, in sickle cell anemia subjects, the frequency was significantly greater and ranged from 0.22 to 0.33. Analysis demonstrated that the greater frequency in the last group was primarily a result of an increased number of subjects with alpha-thalassemia trait (also called homozygous alpha-thalassemia-2). In addition, the frequency of the (-alpha) chromosome was found to increase progressively with age, supporting the hypothesis that alpha-thalassemia is favorable to the survival of subjects with sickle cell anemia. Thus, individuals who inherit alpha-thalassemia and sickle cell anemia may represent a subgroup of patients with a longer life expectancy.

Africa, Western↗
PubMed1983

New antisickling agents.

Sickle cell anemia has variable clinical expression, ranging from benign cases to very severe ones. This situation suggest that, unless a perfect drug is identified, the therapeutic approaches may also vary. Great progress has been made in this last decade in the understanding of the Hb S polymer structure, the kinetics of polymerization and some of the cellular contributions to the disease. This progress has suggested that we could alter the course of the disease by impairing the polymerization of Hb S through three mechanisms: a) interfering in the areas of contacts involved in polymer formation by covalent and non-covalent agents, b) changing the oxygen affinity of Hb S to decrease the changes induced by deoxygenation, c) diluting the Hb S by increasing the MCV of the cells and consequently decreasing its MCHC. This last result is achieved by a modification of the permeability of the red cell membrane.

Anemia, Sickle Cell↗
PubMed1982

Homozygous deletional alpha + thalassaemia associated with unequal expression of the two remaining alpha 1 genes (alpha 1A and alpha 1Q).

A Cambodian family presenting several haemoglobinopathies, Hb E, Hb Q and alpha + thalassaemia, has been investigated. DNA analysis showed that the thalassaemia syndrome corresponds to a leftward type (4.2 kb) deletional form of alpha + thalassaemia. Genotypes found in the family are: propositus -alpha A/-alpha Q, beta A/beta E., mother and older sister alpha A alpha A/-alpha Q, beta A/beta E., father alpha A alpha A/-alpha A, beta A/beta A. The propositus consistently presents an alpha Q/alpha A chain ratio of 60/40 although both chains are products of alpha 1 loci. The relatively higher expression of the alpha Q chain is not observed in the mother and therefore makes it unlikely to reflect anything other than differential expression of the maternal -alpha Q/ and paternal -alpha A/ haplotypes. This observation raises the possibility that both haplotypes are not strictly identical and that the region of the cross-over event is important for alpha gene expression.

Chromosome Deletion↗
PubMed1982

Glucose-6-phosphate dehydrogenase and hemoglobin variants in Kel Kummer Tuareg and related groups. Indirect evidence for alpha-thalassemia trait.

A field study of glucose-6-phosphate dehydrogenase (G6PD) and hemoglobin polymorphisms was performed in 327 subjects belonging to the Kel Kummer, a highly inbred Tuareg tribe of North-East Mali, and to the contact populations. In the Kel Kummer group 11% of the investigated subjects carried the nondeficient G6PD A+ variant. No other G6PD variant was found. Hemoglobin D Ouled-Rabah was found in 21% of the subjects of this group. The presence of an alpha-thalassemic trait was also inferred from indirect evidence. The contact groups (Inedän, Iklan, Kel es Suq and Dausahaq) exhibited different polymorphisms at the G6PD and globin loci, substantiating their belonging to different ethnic stock.

Black People↗
PubMed1981

Minor hemoglobin components in diabetic and uremic patients.

Hemoglobins A1c and A1a+b were measured by an automated chromatographic method in 11 control subjects, 100 diabetics and 30 subjects with renal failure not induced by diabetes. Hb A1c was higher in diabetics than in controls (8.26 +/- 0.31 versus 5.24 +/- 0.28, p less than 0.01) and strongly correlated with blood glucose values for the preceding 4 months. In poorly controlled diabetics, submitted to an intensive therapeutic program, Hb A1c decreased rapidly. Hb A1c was slightly but significantly elevated in the uremic, non-diabetic patients who were not submitted to periodic hemodialysis: 6.42 +/- 0.32, p less than 0.05. It returned, in hemodialyzed patients, to a level not significantly different from the control value. Hb A1a+b was elevated in diabetic subjects (2.43 +/- 0.04 vs. 1.55 +/- 0.01 in controls, p less than 0.001). It was also higher in the uremic patients (2.71 +/- 0.14, p less than 0.001). No decrease occurred in the hemodialyzed patients (3.27 +/- 0.31). Glycosylated hemoglobin values, as routinely estimated and expressed under the name of "Hb A1", should be interpreted with caution in patients with renal failure. Methods discriminating Hb A1a+b have to be used.

Diabetes Mellitus↗
PubMed1981

Impairment of the growth of Plasmodium falciparum in HbEE erythrocytes.

HbE is a beta-chain mutant frequently found among inhabitants of Southeast Asia and surrounding territories. We find that Plasmodium falciparum multiplies more slowly in erythrocytes from individuals homozygous for HbE than in cells from HbA individuals. In contrast, this parasite grows normally in erythrocytes heterozygous for HbE. This is the first direct evidence that suggests what has been suspected on the basis of circumstantial data, that HbE-containing erythrocytes might be advantageous to the carrier in regions with endemic malaria.

Erythrocytes↗
PubMed1981

Sickle gene. Its origin and diffusion from West Africa.

Linked DNA polymorphisms can be used to study the evolution of structural gene mutations. Both the beta S-(beta 6Glu leads to Val) and beta C-(beta 6Glu leads to Lys) genes are common in West Africa. We have analyzed their linkage to a polymorphic Hpa 1 site appearing 3' to the beta-globin gene locus in selected populations from Wes Africa. A large reservoir of beta A-genes linked to 13-kilobase Hpa 1 fragments with a frequency of 17-18% has been identified. In addition, the beta S- and beta C-genes in Togo are found to be tightly linked to the 13-kilobase Hpa 1 fragment, whereas 72% of the beta S-genes in the Ivory Coast reside on the 7.6-kilobase Hpa 1 fragment. These studies are consistent with the selection and expansion of two different chromosomes bearing beta S-genes in at least two physically close, but ethnically separate regions of West Africa, with subsequent diffusion to North, Equatorial, and East Africa.

Africa↗
PubMed1981

[Recent data in the biology of sickle cell disease (author's transl)].

A great deal of work has been in the recent years concerning sickle cell anemia, both its theoretical aspects and its medico-social consequences being involved. From the pathophysiological point of view, investigations have resulted in a better knowledge of the mechanism of the hemoglobin S polymerization. Other factors such as the role of the membrane, the ionic environment, the rheologic conditions have also been emphasized. These known disorders may explain the high clinical polymorphism of the disease. They are also the basis of a research for a potential specific treatment. Two factors have been specially investigated as potentially responsible for a benign course of the disease, namely fetal hemoglobin and an associated alpha-thalassemia. As a new field of investigation, a DNA polymorphism close to the beta-gene and linked to the mutation itself has been demonstrated. It proves the pluricentric origin of this mutation. It is also a tool for antenatal diagnosis of the homozygous forms of the disease using amniotic fluid cells. Finally the possible direct culture of P. falciparum as allowed a better understanding of the equilibrium between malaria and sickle cell anemia.

Anemia, Sickle Cell↗