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C Camaschella

Publications and source records attributed to C Camaschella.

At least 109 records · Page 6Linked to original sources
PubMed1987

Sardinian delta beta zero-thalassemia: a further example of a C to T substitution at position -196 of the A gamma globin gene promoter.

Selective overexpression (50- to 100-fold) in adult erythroid cells of either G gamma or A gamma fetal globin gene is observed in hereditary conditions known as delta beta zero-thalassemia and hereditary persistence of fetal hemoglobin (HPFH). Recently, a C----T change at position -196 of an overexpressed A gamma globin gene from an Italian HPFH was hypothesized, on the basis of indirect evidence, to represent the cause of the functional defect. We now show that the same mutation is present in a different overexpressed A gamma-globin gene from a Sardinian patient with a different syndrome (delta beta zero-thalassemia). The Sardinian A gamma globin gene differs from both the HPFH and the normal A gamma globin gene at nucleotide 1,560 in the noncoding portion of the third exon, where an A is deleted. In addition, the mutant -196 A gamma-globin gene is linked to a normal beta globin gene in HPFH, and to a beta-thalassemic gene (beta 39CAG----TAG) in delta beta zero-thalassemia. These data strengthen the suggestion that -196 mutation is causally linked to the abnormal phenotype and raise the question of whether the same or multiple mutational events are responsible for the appearance of the -196 mutation in different syndromes.

Base Sequence↗
PubMed1986

Italian type of deletional hereditary persistence of fetal hemoglobin.

We report a new type of deletion of the beta globin gene cluster in the Italian population that confers a phenotype of hereditary persistence of fetal hemoglobin (HPFH) to the carriers. This deletion begins approximately 5 kilobases (kb) 5' to the delta globin gene and ends approximately 30 kb 3' to the beta globin gene, in close proximity to the 3' end of an Indian HPFH. In all four previously described HPFH, a repetitive Alu I region 5' to the delta globin gene is largely or completely deleted; the 5' end of the new HPFH is consistent with this common feature. In addition, the finding that Italian and Indian HPFHs, as reported for other groups of deletions, have very close 3' ends, strengthens the idea that common mechanisms may operate in generating these deletions. Finally, we show that, in spite of similar 5' breakpoints, the deletion of Spanish delta beta(0)-thalassemia is at least 8 kb longer than that of Negro HPFH type I, thus ruling out the hypothesis that the overall extent of the deletion might influence the level of gamma globin chain synthesis.

Chromosome Deletion↗
PubMed1984

The beta-globin gene in Sardinian delta beta 0-thalassemia carries a C----T nonsense mutation at codon 39.

Sardinian delta beta 0-thalassemia is an inherited syndrome characterized by the inactivity of the beta-globin gene and the persistent activity of the fetal gamma-globin genes, particularly the A gamma-globin gene. Previous mapping studies with restriction enzymes failed to show any abnormality in the non-alpha globin gene cluster. We have now examined the possibility that this syndrome might result from a single rather than two different defects. Restriction enzyme polymorphisms linked to the delta beta 0-thalassemic non-alpha globin fragments were defined providing the basis for cloning the delta beta 0-thalassemic beta-globin gene from the DNA of a heterozygous patient. This gene appears to carry a C----T single mutation causing the appearance of a stop codon at amino acid position 39 of the beta-globin gene. This mutation was previously reported in beta 0-thalassemic patients, in linkage with different haplotypes. We conclude that Sardinian delta beta 0-thalassemia is the result of two separate mutations, the former one (unknown) responsible for persistent expression of gamma-globin genes, the latter for beta 0-thalassemia.

Base Sequence↗
PubMed1984

A molecular study of a family with Greek hereditary persistence of fetal hemoglobin and beta-thalassemia.

A family was studied in which two inherited defects of the non-alpha-globin cluster segregate: Greek hereditary persistence of fetal hemoglobin (HPFH) and beta-thalassemia. Fragments of the non-alpha-globin cluster from two patients were cloned in cosmid and phage lambda vectors, and assigned to either the HPFH or beta-thalassemic chromosome on the basis of the demonstration of a polymorphic BglII site in the HPFH gamma-globin cluster. The thalassemic beta-globin gene carries a mutation at nucleotide 1 of the intervening sequence I, known to cause beta zero-thalassemia; the beta-globin gene from the HPFH chromosome is entirely normal, both in the intron-exon sequence and in 5' flanking regions required for transcription. As the compound HPFH/beta-thalassemia heterozygote synthesizes HbA, these data prove that the HPFH beta-globin gene is functional, although at a decreased rate; its lower activity is likely to be due to a distant mutation. The HPFH A gamma-globin gene shows only two mutations: a T----C substitution in the large intervening sequence (responsible for the BglII polymorphic site) and a C----T substitution 196 nucleotides 5' to the cap site; the 5' flanking sequence is normal up to -1350 nucleotides upstream from the gene. Circumstantial evidence suggests that the mutation at -196 may be responsible for the abnormally high expression of the A gamma-globin gene.

Base Sequence↗
PubMed1983

Increased proportion of suppressor/cytotoxic (OKT8+) cells in patients with Hodgkin's disease in long-lasting remission.

The distribution of T-lymphocyte subsets in patients with Hodgkin's disease (HD) at diagnosis and in those disease-free off-therapy for over 5 years, was assessed with OKT monoclonal antibodies. In patients at diagnosis, T-cell subsets appeared substantially balanced with only a moderate reduction in the proportion and absolute number of OKT4 (helper/inducer) positive cells, suggesting that the lymphopenia, constantly associated with HD at diagnosis, is mainly due to a reduction in the helper/inducer T-cell subpopulation. In patients off-therapy, a reduced proportion, but normal absolute number, of OKT4+ cells was constantly accompanied by a significant increase in the proportion and absolute number of OKT8+ cells, compared with patients at diagnosis and normal controls (40% +/- 11 versus 24% +/- 7 and versus 23 +/- 6, respectively). Consequently the OKT4/OKT8 ratio, normal or near normal in patients at diagnosis (1.70 versus 2.00), was significantly reduced in patients off-therapy (0.78 versus 2.00, P less than 0.001). These data suggest that in patients with HD at diagnosis, T-cell subpopulations are substantially normal, while a significant abnormality was observed in patients with HD off-therapy and potentially "cured." Further investigations will better elucidate these findings probably related to the cytotoxic radiotherapy and chemotherapy.

Adolescent↗
PubMed1982

Molecular comparison of delta beta-thalassemia and hereditary persistence of fetal hemoglobin DNAs: evidence of a regulatory area?

The hematological phenotypes of several Mediterranean patients with delta beta-thalassemia and hereditary persistence of fetal hemoglobin have been characterized. Although clinical and hematological characteristics are essentially superimposable in all heterozygous delta beta-thalassemics, these patients show typical G gamma/A gamma ratios in their Hb F, ranging from approximately 0.07 in Sardinian to approximately 0.15 in Sicilian and approximately 0.35 in Spanish patients. A gamma Sardinian-(isoleucine-75 leads to threonine) is found in Spanish patients and accounts for all of the A gamma production in heterozygotes, indicating that persistent production of gamma chains occurs cis to the delta beta-thalassemia gene. The molecular heterogeneity of these conditions is demonstrated by restriction enzyme mapping of DNA; Sicilian and Calabrian patients show a deletion starting from the delta-globin intron and extending several kilobases 3' to the beta-globin gene; in Spanish patients the deletion starts approximately 2-3 kilobases 5' to the delta-globin gene and extends well beyond the beta-globin gene. Comparison of these deletions with previously described ones in Negro and in a new Southern Italian case of hereditary persistence of fetal hemoglobin suggests that the deletion of a region centered at a cluster of repetitive sequences approximately 3.5 kilobases 5' to the delta-globin gene may be critical for the persistent expression of high levels of gamma-globin in hereditary persistence of fetal hemoglobin compared to delta beta-thalassemia. The concept that the deletion or mutation of specific areas (rather than nonspecific changes brought about by large deletions in the globin cluster) is important in determining the persistent expression of gamma-globin genes is supported by the finding of a nondeletion type of delta beta-thalassemia in Sardinians.

Chromosome Deletion↗
PubMed1982

G gamma and a gamma globin chain synthesis in bone marrow and peripheral blood of beta-thalassaemia homozygotes.

G gamma, A gamma and beta globin chain synthesis has been investigated in the peripheral blood and bone marrow from eight beta-thalassaemia homozygotes. In five out of eight cases total gamma chain synthesis was higher in the peripheral blood than in the bone marrow; in seven out of eight cases A gamma chain synthesis was markedly higher in the marrow than in the peripheral blood. These data suggest that ineffective erythropoiesis selects F-cells synthesizing the largest amounts of G gamma chains, while A gamma producing cells are preferentially destroyed in the marrow.

Adolescent↗
PubMed1982

Chemotherapy of advanced non-Hodgkin lymphomas: a report of 35 cases.

Thirty-five patients with stage III and IV non-Hodgkin lymphomas, classified according to Lennert have been treated by combination chemotherapy (CVP). Total remission (complete plus partial) was obtained in 68.5% of the cases and complete remission in 28.5%; 73% of the favorable types and 55% of the unfavorable histologic types achieved tumor response: the difference was not statistically significant, perhaps because of the limited number of cases. Median survival was 14 months for the unfavorable histologic types and 28 months for the favorable types; longer survivals were obtained in patients who achieved complete remission. CHOP regimen after CVP in patients refractory to this type of treatment was not satisfactory in our patients.

Antineoplastic Agents↗
PubMed1980

gamma chain composition in five Italian newborns heterozygous for Hb F Malta G gamma-117 His leads to Arg.

The percentage of Hb F Malta G gamma-177 His replaced by Arg and the gamma chain composition have been evaluated at birth and at different times after birth in five Italian newborns heterozygous for this variant. The percentage of Hb F Malta ranged at birth from 24% to 31% of the total Hb F, while the average G gamma/A gamma chain ratio was about 7/3, overlapping the values observed in normal newborns. T gamma chains were detected in three out of five newborns, with a percentage of about 10% of the total Hb F. After birth the Hb F Malta declined faster than the total Hb F; thus, the Hb F decrease during the first 45 d of life is mainly due to the switch-off of the G gamma locus containing the Hb F Malta gene.

Aging↗
PubMed1980

Analysis of the gamma chains in a homozygote for HPFH Negro type and in three related heterozygotes.

The gamma-chain structure of a homozygote for HPFH Negro type, previously described by Acquaye and co-workers, and of 3 heterozygotes of the same family has been evaluated. G gamma and A gamma chains were present in a ratio of fetal type (7/3) in the homozygote and in ratios of 2/3 and 1/1 in the heterozygotes, in agreement with data of the literature. T gamma chains were absent in all the cases. Our results, compared with those previously reported for Negro and Greek HPFH, suggest that the T gamma gene is never linked with the HPFH determinant.

Amino Acids↗
PubMed1979

Electrophoretic separation of A gamma and G gamma human globin chains in Nonidet P-40.

Electrophoresis in cellulose acetate in the presence of 3% Nonidet P-40 can resolve two neutral genetic variants, A gamma and G gamma human fetal globin chains. The ratio of these two chains, determined by densitometry of the electrophoretic strips, is in excellent agreement with the Gly-Ala ratio obtained by chemical analysis of the cyanogen bromide fragment gamma CB3. It is suggested that the detergent binds preferentially to the hydrophobic amino acid segment 133-141 in the A gamma chain, thus masking either a Lys or an Arg residue at the two extremes.

Electrophoresis, Cellulose Acetate↗
PubMed1979

[Biochemical and clinical studies of 2 new Italian cases of Hb G-Ferrara heterozygosis].

The Authors report the data concerning a family coming from Ficarolo (Rovigo). The father and one son were found hematologically healthy, but resulted carriers of Hb G-Ferrara. This is an unstable rare pigment with a replacement in the beta 57 (E-1) helicoidal position. The type and site of the mutation explain the "in vitro" molecular instability; on the other hand, this latter doesn't seem to cause any hematological disorder, even if an increased met-Hb production was found when affected blood was incubated at 37 degrees C for two hours in sterile conditions.

Adult↗