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Biomedical subjects

M Marinucci

Publications and source records attributed to M Marinucci.

At least 37 records · Page 2Linked to original sources
PubMed1983

Molecular mechanisms of human hemoglobin switching: selective undermethylation and expression of globin genes in embryonic, fetal, and adult erythroblasts.

The globin chain synthetic pattern and the extent of DNA methylation within embryonic, fetal, and adult beta-like globin gene domains were evaluated in greater than or equal to 90% purified human erythroblasts from yolk sacs and fetal livers in the 6- to 12-wk gestational period as well as from adult marrows. The 6-wk erythroblasts produce essentially embryonic epsilon chains, whereas the 12-wk erythroblasts synthesize largely fetal gamma globin and the adult marrow erythroblasts synthesize almost exclusively adult beta chains. In all phases of ontogenic development, a strong correlation exists between DNA hypomethylation in the close flanking sequences of globin genes and their expression. These results suggest that modulation of the methylation pattern may represent a key mechanism for regulating expression of human globin genes during embryonic leads to fetal and fetal leads to adult Hb switches in humans. In ontogenic development this mechanism might in turn correlate with a gradual modification of chromatin structure in the non-alpha gene cluster, thus leading to a 5' leads to 3' activation of globin genes in a balanced fashion.

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

The delta beta crossover region in Lepore boston hemoglobinopathy is restricted to a 59 base pairs region around the 5' splice junction of the large globin gene intervening sequence.

Genomic DNA from a hemoglobin (Hb) Lepore Boston (delta 87 Gln beta 116 His) homozygote of Southern Italian origin has been studied in order to map the fusion point between the delta and beta genes. An Ava II restriction endonuclease recognition sequence, located 12 base pairs (bp) downstream from the 5' end of the beta gene large intervening sequence, has been taken as marker of the beta-like portion of the fusion gene. This site was present even in the delta beta gene, allowing the localization of the crossover area to a 59-bp region extending from the first nucleotide of the Leu codon in position 88 to the 11th nucleotide of the large intervening sequence. The analysis of the DNA restriction polymorphisms in the gamma delta beta globin gene region provides evidence that a single mutational event originated the Lepore delta beta genes, at least in the Italian population.

Base Sequence↗
PubMed1981

Hemoglobin bologna (alpha 2 beta 2 61 (E5) lys replaced by met). An abnormal human hemoglobin with low oxygen affinity.

An abnormal human hemoglobin was found in association with beta-thalassemia in a hemolysate from an 11-year-old healthy child living in Bologna (northern Italy). Structural studies demonstrated a previously unreported amino acid substitution, beta 61 (E5) Lys replaced by Met (this is an external residue). The new variant has been named Hb Bologna, and is characterized by a reduced oxygen affinity. Family studies indicated that the variant had been inherited from the father, a 41-year-old male of Southern Italian origin. Also, a brother of the propositus was found to be an abnormal Hb carrier.

Adult↗
PubMed1981

The biosynthesis of hemoglobin G San Josè (beta 7(A4) Glu replaced by Gly).

This report is concerned with the evaluation of hematological parameters and the percentage level of the abnormal hemoglobin (Hb) G San Josè as found in 4 heterozygous carriers from a family of Sicilian origin. Biosynthetic studies and in vitro recombination experiments strongly indicate that abnormal beta chains are synthesized at lower rate than beta A chains and exhibit a minor affinity (relative to beta A chains) for complementary chains in a condition of relative aA chain deficiency. The possibility that the low affinity of beta G chains for a chains may play a decisive role in controlling the level of the abnormal Hb in the peripheral blood of the present non-a-thalassemic abnormal Hb carriers is therefore discussed.

Adult↗
PubMed1981

beta Thalassemia associated with increased HB F production. Evidence for the existence of a heterocellular hereditary persistence of fetal hemoglobin (HPFH) determinant linked to beta thalassemia in a southern Italian population.

A family has been observed in which a beta thalassemia determinant is inherited over three generations together with high Hb F level (8-12%) and increased number of fetal-hemoglobin-containing-cells (F-cells). The values of red cell indices and globin chain synthesis ratios, yet typical of beta thalassemia, were significantly shifted to the normal values when compared with those of typical beta thalassemia heterozygotes belonging to the same family group. The occurrence in these individuals of a heterocellular hereditary persistence of fetal hemoglobin (HPFH) determinant and its linkage relationship with the beta thalassemia is discussed. In the third generation two adult individuals were beta thalassemia homozygotes having inherited a beta thalassemia determinant from one parent and a beta thalassemia together with the HPFH determinant from the other. They showed an extremely mild clinical condition, and 11-12 g/dl of mainly Hb F without having ever required blood transfusions. Virtually all the red cells were F-cells in both subjects. The importance of the coexistence of HPFH determinants capable of increasing the size of the F-cell population in patients affected by homozygous thalassemia is discussed, considering the sensible benefit which derives from enhanced Hb F production in this syndrome.

Adolescent↗
PubMed1980

Post-translational control of human hemoglobin synthesis: the role of the differential affinity between globin chains in the control of mutated globin gene expression.

The interactions between beta-thalassemia and the human hemoglobin (Hb) alpha-chain variants, Hb Hasharon, Hb O Idonesia and Hb J Paris, and between alpha-thalassemia and the beta-chain variants, Hb S, Hb C and Hb G San José, which are characterized by preferential decrease of the abnormal Hb level in peripheral bloods, have been studied. Both biosynthesis studies in reticulocytes and determination of the relative affinity of abnormal chains for normal complementary chains by in vivo recombination experiments, involving globin chains previously isolated in their native form, have been carried out in order to provide insights on the molecular events following the synthesis of the mutant chains under conditions of complementary chain deficiency. Furthermore, we have measured the relative affinity for complementary chain of beta D Los Angeles- and alpha J Rovigo-chains, the level of which does not decay in thalassemic carriers, and of alpha Legnano- and beta Osu Christiansborg-chains, which have not yet been observed in association with thalassemias. Our experiments indicated that the differential affinity for beta-chains is not always the major post-translational control mechanism which regulates the level of certain alpha-chain variants in beta-thalassemic heterozygotes, and that preferential removal of abnormal chains by proteolytic enzymes is likely to play an important role in most cases. On the other hand, the low affinity of certain variant beta-chains for alpha-chains may offer an explanation for the low level of certain beta-chain variants in peripheral blood of non-thalassemic carriers, as well as to their decrease under conditions of relative alpha-chain deficiency (alpha-thalassemias).

Globins↗
PubMed1980

Possible duplication of the hemoglobin alpha chain locus in sheep.

Only one type of alpha chain has been described so far in the hemoglobins of adult domestic sheep. A variant (Hb D) of the alpha chain, characterized by a substitution glycine leads to aspartic acid at position 15, has been described in Yugoslavian sheep. In this paper we report the identification of a second alpha chain (alpha 2), observed in several sheep when the globin was analyzed by CM-cellulose chromatography or the total hemolysate submitted to isoelectric focusing. The ratio of this chain to the usual one (alpha 1) in the globin of different animals is equal to either 1 : 2 or 1 : 4. The structural difference between alpha 1 and alpha 2 chains consists in the replacement of a leucine residue by an histidine in the position 113 or 114 of the polypeptide chain. Preliminary data on the frequency of the alpha 2 chain in eight domestic breeds indicate that this chain is fairly common, being present in 15 out of 40 animals examined. The results of breeding experiments between sheep of an appropriate alpha chain phenotype suggest the possibility of a duplication of the hemoglobin alpha locus in the Ovinae.

Amino Acid Sequence↗
PubMed1980

A new human hemoglobin variant: Hb BARI (alpha 2 45 (CD3) His leads to Gln beta 2).

An alpha-chain variant hemoglobin was found in the hemolysate of a 21-year-old healthy male living in Bari (Puglia, Italy). Structural studies demonstrated a previously unreported amino acid substitution, alpha 2 45 (CD3) His leads to Gln beta 2, involving a distal heme contact. The new variant has been named Hb Bari. Its electrophoretic behavior was the same as for Hb A; it was stable to both isopropanol and heat denaturation and exhibited normal functional properties, with respect to whole blood and stripped hemolysate studies. The level of Hb Bari was about 20% in the observed carrier. No relative was available for further investigations.

1-Propanol↗