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Biomedical subjects

P Colonna

Publications and source records attributed to P Colonna.

At least 91 records · Page 5Linked to original sources
PubMed1989

A study of membrane protein defects and alpha hemoglobin chains of red blood cells in human beta thalassemia.

The soluble pool of alpha hemoglobin chains present in blood or bone marrow cells was measured with a new affinity method using a specific probe, beta A hemoglobin chain labeled with [3H]N-ethylmaleimide. This pool of soluble alpha chains was 0.067 +/- 0.017% of hemoglobin in blood of normal adult, 0.11 +/- 0.03% in heterozygous beta thalassemia and ranged from 0.26 to 1.30% in homozygous beta thalassemia intermedia. This elevated pool of soluble alpha chains observed in human beta thalassemia intermedia decreased 33-fold from a value of 10% of total hemoglobin in bone marrow cells to 0.3% in the most dense red blood cells. The amount of insoluble alpha chains was measured by using the polyacrylamide gel electrophoresis in urea and Triton X-100. In beta thalassemia intermedia the amount of insoluble alpha chains was correlated with the decreased spectrin content of red cell membrane and was associated with a decrease in ankyrin and with other abnormalities of the electrophoretic pattern of membrane proteins. The loss and topology of the reactive thiol groups of membrane proteins was determined by using [3H]N-ethylmaleimide added to membrane ghosts prior to urea and Triton X-100 electrophoresis. Spectrin and ankyrin were the major proteins with the most important decrease of thiol groups.

Erythrocyte Membrane↗
PubMed1989

Advanced Hodgkin disease (clinical stages IIIB and IV): low relapse rate after brief chemotherapy followed by high-dose total lymphoid irradiation.

From January 1980 to September 1986, 50 patients with Hodgkin disease, clinical stages (CS) IIIB (26 cases) and IVB (24 cases) were treated by three cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy, followed by high-dose (40 Gy) (sub)total lymphoid irradiation, including the spleen. Ten patients (2 CS IIIB, 8 CS IVB) were in failure, and seven (4 CS IIIB, 3 CS IVB) died during their first complete remission (2 from treatment-related complications, 1 from unknown cause, 4 from insufficient supportive care and/or a shortage of health supplies); three patients (CS IIIB) relapsed (2 alive in second complete remission, 1 deceased). After 7 years, actuarial survival and relapse-free duration were, respectively, 64% for the 50 patients and 89% for the 40 patients in complete remission. Unfavourable outcome was observed in patients with pelvic nodal involvement. The low relapse rate (none in CS IVB) was the most striking result after brief chemotherapy followed by total lymphoid irradiation.

Adolescent↗
PubMed1989

Insulin and glycemic responses in healthy humans to native starches processed in different ways: correlation with in vitro alpha-amylase hydrolysis.

The aim of the study was to elucidate how extracted starches submitted to food processing (or not) can influence plasma insulin and glucose responses in healthy subjects. Native starches from wheat, manihot, smooth peas, or mung beans were tested either raw, as starch gels (boiled and cooled), or cooked and cooled after a preliminary industrial processing: extrusion cooking for wheat, tapioca for manihot, and noodles for mung beans. Eighteen healthy subjects randomly assigned received three different starches under one form of conditioning. All products were submitted to in vitro alpha-amylolysis. Raw manihot starch produced the lowest (p less than 0.05) metabolic responses. Cooking significantly (p less than 0.01) increased plasma responses. However, cooked mung bean noodles gave metabolic responses similar to those of raw products. Close correlations were found between percentages of in vitro starch hydrolysis at 30 min and mean areas under the glycemic curves and the insulinemic curves (r = 0.95, p less than 0.001).

Adult↗
PubMed1989

Molecular basis of Sp alpha I/65 hereditary elliptocytosis in North Africa: insertion of a TTG triplet between codons 147 and 149 in the alpha-spectrin gene from five unrelated families.

Hereditary elliptocytosis in North Africa is frequently associated with the alpha I/65 spectrin variant, characterized by an abnormal alpha I 65-kD instead of the normal alpha I 80-kD peptide following limited trypsin digestion of whole spectrin. A similar variant (although it yielded a 68-kD fragment) has been shown recently, in two black patients, to result from the insertion of a leucyl residue at position 148 (Marchesi et al: J Clin Invest 80:191, 1987). In order to determine if the underlying molecular defect was the same in North Africans and blacks (who originate from both sides of the Sahara Desert), we performed analysis directly at the DNA level. Starting from the DNA of an Algerian alpha I/65 heterozygote in whom the mutation was associated with identifiable RFLPs, we cloned and sequenced the alpha-spectrin gene region, which includes the mutation. We thus identified an extra leucine codon (TTG) between codons 147 and 149, the coding sequence becoming CAG TTG TTG CTG instead of CAG TTG CTG. We then used the polymerase chain reaction (PCR) method and dot-blot hybridization of the amplified DNA with mutant and normal allele-specific oligonucleotides to screen the DNA from four other unrelated North African subjects with Sp alpha I/65 hereditary elliptocytosis. In all families we studied, these subjects were heterozygous for the TTG insertion. These results demonstrate that Sp alpha I/65 hereditary elliptocytosis has the same molecular basis in North Africans and blacks.

Africa, Northern↗
PubMed1987

Alpha-thalassemia haplotypes in the Algerian population.

DNA mapping was performed in seven unrelated Hb H patients and nine carriers for alpha-thalassemia trait originating from Algeria. This study has allowed us to identify four alpha-thalassemia haplotypes: the (-alpha 3.7) haplotype, which is the most frequent (18 of 23 alpha-thalassemic chromosomes), the (-(alpha)20.5) haplotype, a (--) haplotype, and an (alpha alpha)T haplotype. Our results also show that the (-alpha 3.7) haplotypes encountered in the Algerian population are heterogeneous and differ by the site of the unequal crossover responsible for the 3.7-kb deletion and the size of the interzeta fragment. In addition, during this survey we observed that normal chromosomes bearing a polymorphic BglII site are associated with different interzeta fragments.

Algeria↗
PubMed1987

Gerbich reactivity in 4.1 (-) hereditary elliptocytosis and protein 4.1 level in blood group Gerbich deficiency.

The membrane polypeptide composition and the blood group Gerbich phenotype of red cells from 4.1 (-) hereditary elliptocytic patients and from Gerbich-negative donors, who display two unrelated genetic abnormalities, were compared. In homozygous 4.1 (-) hereditary elliptocytosis where the primary defect was presumably the absence of the membrane skeletal protein 4.1, there was approximatively a 70% reduction in the minor sialoglycoproteins beta and gamma. This was associated with a severe reduction of blood group Gerbich reactivity as determined with both murine monoclonal and human anti-Gerbich antibodies. In the heterozygous state in the presence of one haploid set of protein 4.1 gene there was only a modest decrease in glycoproteins beta and gamma and the Gerbich serological reactivity was within normal limits. In homozygous Gerbich-negative red cells which lack glycoproteins beta and gamma but do not display elliptocytic red cells, the levels of protein 4.1 was repeatedly found within or just below the lowest values of normal controls. In the heterozygous Gerbich-negative conditions, glycoproteins beta and gamma were present in reduced amounts but the blood group Gerbich reactivity fell within normal limits since the anti-Gerbich reagents used were unable to detect a dosage effect. The amount of protein 4.1 was normal. These results add further support to the view that protein 4.1 and the sialoglycoproteins beta and gamma are physically linked in vivo which in some way serve to maintain red cell shape and integrity. Of interest was the finding that absence of protein 4.1 had a greater influence on the level of membrane glycoproteins beta and gamma than did the absence of beta and gamma glycoproteins on band 4.1.

Blood Group Antigens↗
PubMed1987

Hodgkin's disease, clinical stages IA to IIIB: combined modality therapy (3 MOPP followed by curative and prophylactic radiotherapy including the spleen). Six-year results.

From January 1980 to September 1985, 82 patients with IA to IIIB clinical stage (CS) Hodgkin's disease were treated by three MOPP chemotherapy (CT) cycles followed by extended field radiotherapy (RT) including the spleen (30-40 Gy). 2 patients died during the treatment (medullary aplasia, pulmonary edema). 6 were in failure after three MOPP cycles; they received other CT; 3 died and 3 are alive in remission (survival: 2.5 to 3.5 yr). 74 were in complete remission (CR) after completion of treatment. 4 patients relapsed (all alive after re-treatment) and 4 died in first CR (tuberculosis, hepatitis, myeloma, unknown cause). At 6 yr, actuarial survival and relapse-free survival are respectively 89.8% for the 82 patients and 93% for those in CR. These good results are due to: the administration of CT before RT, limited to three cycles; identification of failures after CT; inclusion of the spleen in RT ports in all cases; and a short lumbo-aortic port in CS I and II.

Combined Modality Therapy↗
PubMed1986

[Treatment of Hodgkin's disease by chemotherapy with MOPP alone. Long-term results].

Between 1967 and 1978, 152 Algerian patients (31 children and 121 adults) with Hodgkin's disease were treated with the mechlorethamine, vincristine, procarbazine, prednisone combination (MOPP) alone and without radiotherapy. They were separated without lymphography into limited stage (n = 37) and extensive (n = 115) stage. The high initial failure rate (54%) was principally due to inadequate symptomatic treatment and to the patients' low socio-economic status. The complete remission rate was 45% (54% for limited stages; 42% for extensive stages) and significantly higher in women (58%) than in men (37%). In 20/23 cases relapses occurred during the first 4 years of complete remission; however, the final relapse was observed during the 12th year of complete remission. The actuarial relapse rate at 15 years was 48%. The long-term (10-15 years) life expectancy was 31% overall and 70% in cases with complete remission. Prognosis was significantly better in patients with limited forms and/or without systemic symptoms.

Adolescent↗
PubMed1986

Sp alpha I/65 hereditary elliptocytosis in North Africa.

The Sp alpha I/65 variant of the spectrin has been recently described in black people with hereditary elliptocytosis (HE). The present study reports on a similar Sp alpha I/65 variant in nine North African persons belonging to four unrelated families. The abnormality was associated with a variable degree of elliptocytosis. In one case, red cell morphology was normal. In the nine carriers of the biochemical abnormality, the spectrin dimer self-association was defective. The association constant was reduced: 0.65 to 1.7 X 10(5) M-1 (controls: 4.6 +/- 0.5 X 10(5) mM-1 (n = 21)); in six cases, there was a higher level of spectrin dimer in the low ionic strength extract at 4 degrees C: 13.0 to 19.7% (controls: 6.4 +/- 2.1% (n = 7)). Limited tryptic digests of spectrin from the nine persons revealed a decrease of the 80,000-dalton alpha-1 domain, and the concomitant appearance of a peptide with a molecular weight of 65,000 daltons and an isoelectric point ranging from 5.0 to 5.1. There was a correlation between the proportion of the 65,000-dalton fragments, the defect of spectrin self-association, and the extent of morphological alteration. This is the first large series concerning a spectrin abnormality in non-black persons. In North Africa, cases of HE that are not due to a protein 4.1 defect have turned out so far to be associated with the Sp alpha I/65 variant.

Algeria↗
PubMed1985

Red cell membrane sialoglycoprotein beta in homozygous and heterozygous 4.1(-) hereditary elliptocytosis.

Sialoglycoprotein beta, a minor sialoglycoprotein of the red cell membrane, was studied in homozygous and heterozygous 4.1(-) hereditary elliptocytosis, a variety of hereditary elliptocytosis characterized by total or partial absence of protein 4.1. Erythrocytes were treated with the periodic acid-NaB3H4 procedure. Following polyacrylamide gel electrophoresis in the presence of SDS, labelled sialoglycoproteins were revealed by fluorography. (i) In the ghosts from the 4.1(-) homozygote, sialoglycoprotein beta was sharply decreased. It is not sure whether the residual material is sialoglycoprotein beta itself, or a distinct sialoglycoprotein migrating in the same place. In long exposure fluorograms, sialoglycoprotein gamma (a sialoglycoprotein related to sialoglycoprotein beta) also turned out to be reduced. In the homozygote's Triton-shells, sialoglycoprotein beta and gamma appeared completely absent. (ii) In the 4.1(-) heterozygote, sialoglycoprotein beta appeared slightly reduced, whereas sialoglycoprotein gamma appeared normal. Both of these proteins were extracted in seemingly normal amounts in the Triton-shells. These observations bring further support to the view that there is an interaction between skeletal membrane protein 4.1 and sialoglycoprotein beta, that is additional to other interactions between the former protein and the lipid bilayer and/or other transmembrane proteins.

Adolescent↗
PubMed1985

Alpha globin gene triplication in severe heterozygous beta thalassemia.

In an Algerian family, three sibs with an unusually severe heterozygous beta-thalassemia and two sibs with a typical heterozygous beta-thalassemia were found. Both conditions were transmitted vertically. Globin chain synthesis and DNA restriction enzyme analysis showed that the unusual severity of heterozygous beta-thalassemia observed in this family is related to an overproduction of alpha-globin chains originating from an alpha-globin gene triplication.

Adolescent↗
PubMed1985

The heterozygous form of 4.1(-) hereditary elliptocytosis [the 4.1(-) trait].

Using clinical, morphological, genetic, and biochemical criteria, we studied ten white and North African families with hereditary elliptocytosis (HE). In four families, elliptocytic individuals displayed a highly significant reduction of band 4.1, which was recorded using two electrophoretic procedures. The 4.1a/4.1b ratio was also significantly reduced, as is usually observed in suspensions enriched in young red cells. This form of HE was invariably associated with the following characteristics: absence of clinical signs; numerous, smooth and well-elongated elliptocytes; dominant transmission; and, when investigated, normal osmotic fragility. Its frequency, among all forms of HE, is about one third as a first estimate, at least in whites and North Africans. In the other six families studied, elliptocytic subjects presented normal 4.1 bands. Again, the 4.1a/4.1b ratio was decreased, reflecting the red cell age-dependent changes in these two components. In three of these families, elliptocytosis was accompanied by clinical signs of variable intensity, and the mode of inheritance could not be unequivocally determined. Therefore, HE with a partially reduced band 4.1 defines a homogeneous variety of HE that can be isolated from other forms of HE. We suggest that it be termed the 4.1 (-) trait, so as to correspond with a previously proposed terminology.

Adolescent↗
PubMed1984

Sickle cell beta-thalassaemia compared with sickle cell anaemia in Algeria.

Clinical, haematological and biochemical features in 42 subjects with S-beta thalassaemia (31 subjects with S-beta thalassaemia and 11 subjects with S-beta+ thalassaemia); and in 42 with homozygous sickle cell disease were compared. Persistent splenomegaly was more common and painful crises less common in the S-beta thalassaemia group. Total Hb was higher and reticulocyte count lower in S-beta+ thalassaemia than in S-beta thalassaemia or SS disease. Microcytosis was marked in the S-beta thalassaemia group while the MCV was normal in sickle cell anaemia. Hb F was significantly higher in the S-beta thalassaemia group, without any influence on the severity of the disease. Many features suggest that sickle cell thalassaemia is more severe in Algeria than in Negro subjects and similar to the disease in Italian patients.

Adolescent↗