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Biomedical subjects

J Rosa

Publications and source records attributed to J Rosa.

At least 127 records · Page 7Linked to original sources
PubMed1982

Structural study of hemoglobin Knossos, beta 27 (B9) Ala leads to Ser. A new abnormal hemoglobin present as a silent beta-thalassemia.

A new electrophoretically silent hemoglobin variant is described that produces the classical phenotype of beta thalassemic intermedia in association with beta thalassemia trait. This variant has the expression of a silent beta thalassemia trait. The abnormal hemoglobin was detected by acid-urea-Triton-acrylamide electrophoresis and further demonstrated by isoelectric focusing. The amount of the variant in carrier is approximately 30% of the total hemoglobin. No instability was found. Absence of hemoglobin A in the propositus blood facilitated structural studies. Peptides maps were normal but analysis of individual peptide spots showed an Ala leads to Ser substitution in the beta T3. This variant has been previously called Hb Knossos (beta 27 (B9) Ala leads to Ser).

Amino Acids↗
PubMed1982

A new silent hemoglobin variant in a black family from French West Indies, hemoglobin Le Lamentin alpha 20 His replaced by Gln.

A new abnormal hemoglobin Hb Le Lamentin alpha 20 (B1) His replaced by Gln was discovered during a survey of cord blood from the French West Indies (Martinique). This variant displays an electrophoretic pattern similar to that of Hb A but can be isolated by isoelectric focusing (IEF) and Biorex 70 chromatography. Family studies showed the presence of this hemoglobin variant in the father and in two of his three children. Hematological data from the carriers were normal.

Adult↗
PubMed1982

An update on electrophoretic and chromatographic methods in the diagnosis of hemoglobinopathies.

This review primarily deals with methods for separations of hemoglobins. An introduction considers electrophoretic methods as well as those involving isoelectric focusing and chromatography. The main advantages or disadvantages of each procedure are discussed after each technical description. The chromatographic methods are mainly limited to those used in clinical biochemistry. The second section treats the main diagnostic problems typically met with in the field of the hemoglobinopathies and deals successively with the diagnosis of hemoglobinopathies in the adult and the newborn. Numerous variants have been described in the adult, and among them Hb-S and Hb-C variants are the most frequent. Unstable or high oxygen affinity variants of hemoglobin are also considered. Finally, a new strategy for diagnosis is proposed. A special section is devoted to the diagnosis of thalassemia syndromes. The prenatal diagnosis of hemoglobinopathies is also discussed in some detail with a view to preventing the birth of homozygous children. This update ends with a chapter on the interest of the assay of hemoglobins A1c in the pathology of diabetes mellitus.

Adult↗
PubMed1982

Hb switching in neonatal cultures. Increase of Hb A synthesis in presence of an erythroid potentiating activity (EPA).

The role of EPA (erythroid potentiating activity) on the growth and on the pattern of hemoglobin synthesis in erythroid colonies from human neonates was investigated. Conditioned medium from the Mo cell line was used as a source of EPA. The results have shown that the addition of Mo medium to cultures determined a significant enhancement of the number and size of BFU-E and an increase of beta chain synthesis. The acceleration of hemoglobin switching is not related to an amelioration of the maturation of the erythroid colonies when grown in the presence of Mo medium. The enhancement of Hb A synthesis induced by Mo medium can directly be related to its EPA, which may operate by two different mechanisms: (1) the recruitment of early erythroid progenitors already preprogrammed to synthesize prevalently beta chains, or (2) the modulation of beta and gamma gene activity in cord blood BFU-E. Some evidence suggests that the first mechanism does operate.

Cell Differentiation↗
PubMed1982

Effect of thyroid hormones on the switch from larval to adult hemoglobin synthesis in the salamander Pleurodeles waltlii.

The evolution of globin chain synthesis was studied in larvae treated either with thyroxine or with an anti-thyroid substance. Thyroxine treatment accelerated the rate of Hb switching; it induced a preferential synthesis of adult globins while the synthesis of larval globins decreased rapidly. Treatment with thiourea did not prevent the Hb transition, which occurred even at concentrations of thyroid hormones that did not permit induction of anatomical metamorphosis.

Animals↗
PubMed1982

Hemoglobin expression in clones of K562 cell line.

The K562 cell line was cloned by dilution and the pattern of hemoglobin (Hb) production was analyzed in the clones thus obtained. The pattern of hemoglobin synthesis was different from one clone to another. According to the Hb phenotype the clones were classified in three main groups; group I no detectable Hb; group II Hb Portland; group III Hb Portland + Hb Gower I. The addition of hemin induced a better hemoglobinization and a shift in the pattern of Hb production: clones of group I were induced to produce Hb Portland and clones of group II to synthesize Hb Gower I. A constant order in the sequential expression of the different hemoglobins was observed: no Hb leads to Hb Portland + Hb Gower I. The proportion of the different globin chains varied from one clone to another, but an inverse correlation between the synthesis of G gamma and epsilon chains was observed. The alpha/non-alpha chain ratio was unbalanced in all the clones and the addition of hemin induced only a moderate increase of the synthesis of alpha chains. Recloning of three primary clones increased the homogeneity of the hemoglobin pattern, in particular after hemin induction.

Clone Cells↗
PubMed1982

Binding of 21 thiol reagents to human hemoglobin in solution and in intact cells.

The reactivity of the cysteine-beta 93 residue of human hemoglobin was investigated in order to define the optimal structure of potential antisickling agents. The properties of 21 thiol reagents were compared with regard to (a) their binding rate to hemoglobin in solution and within intact cells; (b) the modification of the oxygen dissociation curve of intact cells and (c) the effect on methemoglobin formation in solution or within intact cells. The results show the very different behaviors of these reagents.

Adult↗
PubMed1982

Lasting Hb F reactivation and Hb A2 reduction induced by the treatment of Hodgkin's disease in a woman heterozygous for beta-thalassemia and the Swiss type of the heterocellular hereditary persistence of Hb F.

A remarkable augmentation of Hb F and a reduction of Hb A2 were observed in a Sicilian woman during and after a course of treatment for Hodgkin's disease. An inverse correlation between the proportion of Hb F and Hb A2 was found over an 8-year period, as well as in populations of red blood cells fractionated by density gradient. She exhibited two genetic defects, the Swiss type of heterocellular hereditary persistence of fetal hemoglobin and a beta-thalassemia trait, which were confirmed by the study of the hemoglobin synthesis and by a family study. The lasting reactivation of Hb F synthesis is attributable to the interaction of several acquired and inherited factors.

Adult↗
PubMed1982

A new case of phosphoglycerate kinase deficiency: PGK Creteil associated with rhabdomyolysis and lacking hemolytic anemia.

A new case of phosphoglycerate kinase (PGK) deficiency is described. The propositus displayed episodes of rhabdomyolysis crises and acute renal failure but did not exhibit any sign of hemolysis. A severe deficiency in phosphoglycerate kinase was revealed in muscle and was also found in erythrocytes, white cells and platelets. A partial defect in the same enzyme was present in the mother's and the two daughters' erythrocytes, indicating a X-linked recessive genetic transmission of the enzyme defect. In the propositus, erythrocyte ATP concentration was normal, although 2,3-diphosphoglycerate and triose phosphate levels were moderately increased. Lactate production from glucose, in vitro, was close to normal in intact red cells. The partial PGK was characterized by an increased Km for ADP and more especially for ATP, reduced thermostability, and diminished electrophoretic mobility. Lack of this enzyme, which is a key step in the glycolytic process (generation of one molecule of ATP), is thought to be responsible for rhabdomyolysis, a fact that has not been reported previously.

Acute Kidney Injury↗
PubMed1981

[Detection of haemoglobinopathies at birth, using isoelectric focalization (author's transl)].

The incidence and nature of haemoglobinopathies were investigated at birth in Martinique, where 4635 samples of umbilical cord blood were examined. Conventional blood values were determined, and a new, extremely simple and highly selective test was performed: isoelectric focalization. Abnormalities were found in 14.3% of blood samples, viz: A/S 7.25%, A/C 3.17%, S/S 0.17%, S/C 0.24%, C/C 0.04%, other mutations 0.63% alpha-thalassaemia minor (alpha 1-thal) 1.72% and isolated microcytosis 1.01%. Unusual abnormalities included 7 different mutations of the 4a-chain, 3 of the beta-chain and 3 of the gamma-chain. The clinical and epidemiological importance of such investigations is emphasized.

Fetal Blood↗
PubMed1981

Functional studies of two new abnormal hemoglobins with their mutation located at intersubunit contacts: Hb Hotel Dieu beta99 (G1) Asp replaced by Gly and Hb Pitie Salpetriere beta34 (B16) Val replaced by Phe.

The functional properties of two new abnormal hemoglobins with high oxygen affinity were studied. Hb Hôtel Dieu beta99 (G1) Asp replaced by Gly is situated in the alpha1beta2 contact. Hb Pitié Salpétrière beta34 (B16) Val replaced by Phe is situated in the alpha1beta1 contact. Both hemoglobins exhibited similar functional properties with a 10-fold increased oxygen affinity, a decreased cooperativity, a decreased Bohr effect and a normal or slightly decreased 2,3-diphosphoglycerate effect. The structure-function relationship is discussed in the light of these results.

2,3-Diphosphoglycerate↗
PubMed1981

The structure of hemoglobin Creteil (beta 89 Ser replaced by Asn) is similar to that of abnormal human hemoglobins having sequence changes at Tyr 145 beta.

In normal deoxyhemoglobin A, the beta chain COOH-terminal peptide adopts a well ordered structure which is needed for the full expression of allosteric action. Our crystallographic studies of deoxyhemoglobin Creteil (beta 89 Ser replaced by Asn), a variant hemoglobin characterized by high oxygen affinity and a very low level of allosteric function, show that replacement of Ser 89 beta by asparagine causes severe disordering of the beta chain COOH-terminal tetrapeptide. This results, as shown by our spectroscopic studies, in the destabilization of the quaternary structure of deoxyhemoglobin Creteil. We find, furthermore, that the changes in tertiary structure observed in deoxyhemoglobin Creteil are common to other variant hemoglobins having similar functional abnormalities but very different changes in primary structure. In particular, direct comparison of the difference electron density map of deoxyhemoglobin Creteil with that of deoxyhemoglobin Nancy (beta 145 Tyr replaced by Asp) suggests that these two abnormal hemoglobins may have the same mechanism of dysfunction despite the very different nature of their respective sequence changes.

Amino Acid Sequence↗
PubMed1981

[Antenatal diagnosis of sickle-cell anaemia by DNA analysis of amniotic fluid cells. A preliminary study in the French West-Indies (author's transl)].

The genetic polymorphism previously reported to be associated with the sickle-cell (beta S) gene in black U.S.A. citizens was studied in the population of two French West-Indies islands in order to evaluate its potential application to the antenatal diagnosis of sickle-cell anaemia. The polymorphism consists of a change in the DNA sequences located near the 3' end of the beta globin gene. The change can be detected by means of the restriction endonuclease Hpa I. When cellular DNA is digested with this enzyme, the beta globin gene is contained in a DNA fragment measuring either 7.6 or 13.0 kilobases (kb). In 70% of SS homozygous subjects in Martinique and 57% in Guadeloupe the beta S gene was carried by a 13.0 kb DNA fragment, whereas the normal beta A gene was carried by a 7.6 kb DNA fragment. This polymorphism would make it possible to detect the foetal beta S gene in the DNA of amniotic fluid cells by linkage analysis.

Amniotic Fluid↗