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G Boffa

Publications and source records attributed to G Boffa.

6 recordsLinked to original sources
PubMed1991

Cloning of the gene encoding the human erythropoietin receptor.

The genomic and complementary DNAs of the human erythropoietin receptor (hEpo-R) have been isolated and characterized from a genomic placental library and from two cDNA libraries prepared from bone marrow and fetal liver. The five different partial cDNAs isolated were aberrant in the predicted reading frames as compared with the Epo-R protein sequence, because all retained insert sequences that may represent splicing intermediates (three clones), cloning artifact (one clone), or a new sequence at a splice junction (one clone) of the gene. The cDNAs were used to isolate several genomic clones encompassing the complete hEpo-R gene. This gene, which encodes a 508-amino acid polypeptide chain of predicted M(r) 55,000, is organized into eight exons spread over 6 kb of DNA and exhibited a high degree of sequence homology (81.6% in the coding region) and structural organization with its murine counterpart. Primer extension analysis indicated that the transcription initiation site is located 141 bp upstream of the initiation codon. Sequence homology 320 bp upstream of the cap site was significantly lower (60%) and diverged completely further upstream as compared with the murine gene. Similarly, the human and murine sequences were largely divergent downstream of the stop codon, indicating that a strong conservation during evolution was restricted to the coding sequence of the Epo-R protein. The 320-bp region upstream of the cap site does not contain the typical TATA or CAAT boxes present in many tissue-specific genes, but does include potential binding sites for the ubiquitous Sp1 and the erythroid-specific GATA-1 trans-activating factors. These boxes are well conserved in sequence and position relative to the cap site within the promoter region of the human and murine genes, but the CACCC boxes present in the murine gene are absent in the human gene.

Animals↗
PubMed1988

[A clinical case].

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Angina Pectoris↗
PubMed1987

Polycythemia in chronic obstructive pulmonary disease. A study of serum and urine erythropoietin and medullary erythroid progenitors.

In order to investigate the mechanism of polycythemia in chronic obstructive pulmonary disease (COPD), serum and urinary levels of erythropoietin and medullary erythroid progenitors were studied in 21 patients; nine were nonpolycythemic (hematocrit, 39 +/- 4 percent; red blood cell [RBC] mass, 28 +/- 5 ml/kg; forced expiratory volume in one second [FEV1], 0.6 +/- 0.1 L), and 12 patients were polycythemic (hematocrit, 52 +/- 7 percent; RBC mass, 46 +/- 7 ml/kg; FEV1, 0.9 +/- 0.3 L). Hypoxia was severe in both groups, with mean arterial oxygen pressure of 47 mm Hg. The following parameters of tissue oxygenation were not significantly different between the two groups: arterial and mixed-venous oxygen saturations; cardiac output; oxygen utilization coefficient; 2, 3-diphosphoglycerate, and carboxyhemoglobin level. The level of erythropoietin was measured by bioassay in vitro. The level was increased in the serum of 85 percent (18) and in the urine of 38 percent (8) of the patients. There was no significant difference between the nonpolycythemic and polycythemic groups. Without exogenous erythropoietin, none of the subjects showed spontaneous colonies of erythroid progenitors. The addition of one unit of erythropoietin induced a similar normal proliferation of erythroid progenitors in both groups. The absence of adaptative polycythemia in the nonpolycythemic group with severe hypoxia was seemingly related neither to a quantitative deficit of erythropoietin nor to a lack of sensitivity of erythroid progenitors to its action.

Aged↗
PubMed1986

A prospective study of the value of bone marrow erythroid progenitor cultures in polycythemia.

The diagnostic value in polycythemia of the presence of endogenous erythroid colonies derived from bone marrow cells (EECs) was assessed in a prospective study on 108 patients referred for polycythemia (Hb greater than g/dL in men, greater than 16 g/dL in women) with normal plasma volume by comparison with the standard criteria, the bone marrow grade, and the serum erythropoietin (Epo) level. Total red cell volume (TRCV) was high (greater than 36 mL/kg in men, 32 mL/kg in women) in 87 cases (group A) and slightly increased in 21 cases (group B). Standard criteria were applicable in 63 of 108 cases (57%); 46 were PV and 17 were secondary polycythemia (SP). Standard criteria were nonapplicable in 45 cases. EECs were present in 65 cases (60%) with a ratio of EEC/Epo-stimulated colonies of 39.5% +/- 18% (extremes 10% to 80%). EECs were noted in 43 of 46 polycythemia vera (PV) and 0 of 17 SP. Among the 45 unclassified cases, EECs were noted in 22: 18 of 29 cases from group A (10 with 2 major and 1 minor criteria; 8 with 2 major criteria) and 4 of 16 cases from group B (with variable standard criteria, 2 belonging to a PV family). In group A, there was a positive significant correlation between EECs and the presence of two major and 1 minor criteria (P less than .0001). In group B, there was a positive significant correlation between EECs and the presence of at least 1 major criterion and 2 minor criteria or a family background (P less than .0001). The unclassified polycythemias with EECs in the bone marrow are characterized by a bone marrow grade and a mean serum Epo level not different from that of patients with PV and an active course of the disease. The unclassified polycythemias without EECs in the bone marrow are a heterogeneous group corresponding in some cases to SPs of unknown origin (slightly increased bone marrow grade and/or high serum Epo level), and in others cases to spurious polycythemias (normal bone marrow grade and/or normal Epo level). In conclusion, EECs were of great value in differentiating PV from SP (P less than .001), and in allowing the diagnosis of PV in the absence of all the standard criteria even when TRCV was slightly increased. In our study, EEC improved the classification of polycythemia by 22%. The recommended diagnostic steps for the evaluation of polycythemia must be reconsidered.

Adult↗