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Biomedical subjects

A Cao

Publications and source records attributed to A Cao.

At least 289 records · Page 16Linked to original sources
PubMed1981

Genetic and molecular diversity in nondeletion Hb H disease.

Restriction endonuclease mapping of nondeletion alpha-thalassemia determinants from a variety of racial groups showed no detectable abnormalities within a 40-kilobase region of the zeta-alpha globin gene cluster. By using a zeta-specific probe, we defined three different types of interactions that give rise to Hb H disease, each involving a nondeletion alpha-thalassemia haplotype. mRNA analysis showed further diversity within these groups, indicating that there are at least three nondeletion determinations.

Chromosome Deletion↗
PubMed1981

Beta-Thalassaemia types in southern Sardinia.

In this study the prevalence of the different beta-thalassaemia types in southern Sardinia was investigated by cellulose acetate and agar gel electrophoresis or globin chain synthesis analysis on column chromatography or both in (1) all the patients (347) presenting with thalassaemia major or intermedia at our haematology service from 1976 to 1979, and (2) a group of 82 patients with transfusion-dependent thalassaemia major randomly chosen from 236 under our care. Apart from six subjects with delta(beta)0/beta+-thalassaemia genotype and eight with beta0/beta+ or less probably beta+/beta/-thalassaemia, all thalassaemia major and intermedia patients studied were beta0-thalassaemia homozygotes. Globin chain synthesis on peripheral blood cells from these patients, performed at different intervals from blood transfusion, showed no incorporation of radioactive leucine into beta-globin peak, the same as before the transfusion. No correlation between kappa/gamma ratios and clinical severity or hypersplenism was found. Globin chain synthesis analysis carried out at birth in three infants later found to have homozygous beta0-thalassaemia demonstrated imbalanced or borderline kappa/gamma ratios.

Blood Transfusion↗
PubMed1981

Prenatal diagnosis of thalassaemia major resulting from Lepore/ beta-thalassaemia genotype.

Antenatal diagnosis was carried out in a pregnancy at risk for beta-thalassaemia major/intermedia, resulting from the Lepore/ beta-thalassaemia genotype, by globin chain synthesis analysis on fetal blood obtained by placentocentesis at 19 weeks' gestation. As there was no radioactive incorporation in the beta-region, the fetus was considered to be a Lepore/ beta-thalassaemia genetic compound and aborted on parental request. After abortion, cord blood analysis confirmed the absence of beta-chain radioactivity.

Female↗
PubMed1981

Chronic liver disease in transfusion-dependent thalassemia: liver iron quantitation and distribution.

The quantitative and/or qualitative distribution of liver iron was assessed in 81 transfusion-dependent thalassemia major patients with chronic liver disease (36 with chronic active hepatitis, 23 with chronic persistent hepatitis, 22 with siderosis). Viral marker studies showed only 3 cases with both HBsAg and anti-HBc positivity in the serum, while the others had anti-HBc and anti-HBs or only anti-HBs or no B viral markers. A significantly higher iron overload was found in chronic hepatitis, particularly chronic active hepatitis, than in siderosis. The increased iron overload may be due to less intensive chelation treatment, higher intestinal absorption secondary to lower mean Hb levels, and/or to liver inflammation-dependent iron deposition. The liver iron overload in turn amy facilitate the development or persistence of chronic progressive liver disease.

Adolescent↗
PubMed1981

beta zero thalassemia in Sardinia is caused by a nonsense mutation.

We report the characterization of a molecular lesion of beta thalassemia in Sardinia. Beta thalassemia in this area is predominantly the beta zero type with low levels of beta-globin mRNA. Translation assay of this messenger RNA in a cell-free system showed beta-globin chain synthesis only with the addition of an amber (UAG) suppressor transfer RNA. Double-stranded complementary DNA prepared from reticulocyte mRNA from a Sardinian patient was cloned in a bacterial plasmid and a beta-globin complementary DNA containing clone was isolated and sequenced. At the position corresponding to amino acid number 39, a single nucleotide mutation converted a glutamine codon (CAG) to an amber termination codon (UAG). We previously reported an amber nonsense mutation at amino acid 17 as a cause of Chinese beta zero thalassemia. Thus, beta zero thalassemia in Sardinia represents the second example of a nonsense mutation, and we predict that other beta zero thalassemias with mutations at various points along the beta-globin chain will be found to form a discrete subgroup of beta zero thalassemia. These experiments further illustrate the heterogeneity of lesions that lead to defective globin chain synthesis in beta thalassemia.

Bacteriophage lambda↗
PubMed1981

Glucose-6-phosphate dehydrogenase red blood cell phenotype in GdMediterranean heterozygous females and hemizygous males at birth.

The distribution of red blood cell G6PD phenotype was studied by means of the methemoglobin elution test in newborn (46) and adult (50) GdMediterranean heterozygous females and newborn (20) and adult (30) hemizygous males. Newborn heterozygotes had a statistically significant (P less than 0.0005) lower mean red blood cell G6PD enzymatic activity (3.23 +/- 1.04) than did normal newborns (8.78 +/- 1.91), whereas there was no significant difference (P greater than 0.30) from the mean of adult heterozygotes (2.93 +/- 0.86). Like adults, newborn heterozygous females showed: (1) a clear correlation (P less than 0.001) between the percentage of enzyme-deficient red blood cells and G6PD enzymatic activity; and (2) the expected two red blood cell population, i.e., one deficient and the other normal (mosaicism). However, in newborns, the distribution of the subjects according to G6PD-deficient red blood cell percentage (mean percent, 43.67) was significantly shifted (P less than 0.025) in favour of the normal phenotype, unlike adult heterozygotes, who showed a symmetrical distribution of G6PD positive and negative red blood cells (mean percent G6PD-deficient red blood cells, 53.27; P greater than 0.20). Newborn hemizygous males showed a consistent percentage (average, 8.28 +/- 2.2) of stained red blood cells due to the presence of young erythrocytes (pseudomosaicism) unlike the occasional stained cells (less than or equal to 5) seen in adults. The prevalence of hyperbilirubinemia in hemizygous males and heterozygous females was 10.22 and 2.2%, respectively, whereas in G6PD normal newborns it was 5.1%. The practical implication of this study is that the diagnosis at birth of the heterozygous state for G6PD deficiency of the Mediterranean type may be more difficult than in adults. Therefore, very sensitive methods, such as the methemoglobin elution test, should be carried out.

Erythrocytes↗
PubMed1981

Isoelectric focusing of globin chains for antenatal diagnosis of beta 0-thalassemia.

A recently developed isoelectric focusing technique for human globin chain separation has been applied to the antenatal diagnosis of beta 0-thalassemia in Sardinia. Results obtained with this method show a complete concordance with those obtained by the currently-in-use chromatographic separation of globin chains by carboxymethyl-cellulose. The ease with which several samples (up to 20) can be simultaneously processed and analyzed by a single operator and the very simple equipment required make this new method ideal for the antenatal diagnosis of beta 0-thalassemia and could encourage a more widespread use of prenatal diagnosis of thalassemias.

Anemia, Sickle Cell↗
PubMed1981

Diagnosis of the beta 0 thalassemia trait at birth.

This study shows the results of in vitro globin chain synthesis analysis in 33 infants who had been previously evaluated for the presence of thalassemia in the second trimester of gestation and were restudied after the stage of hematological maturity. Four children with alpha-thalassemia-1, identified in a newborn screening, were also included. Normals and beta-thalassemia heterozygotes could be distinguished in the neonatal period by beta/alpha or beta/gamma ratios. However, as a considerable overlap of alpha-thalassemia-1 with normals and alpha-thalassemia-2 with beta-thalassemia heterozygotes were found, biosynthetic studies at birth seem to be inappropriate to make reliable diagnosis of hemoglobin chain deficiencies. There were no differences between hematological indices of normal and heterozygous beta-thalassemia newborns, while alpha-thalassemia-1 carriers showed a statistically significant difference from normals in mean MCV and MCH.

Female↗
PubMed1981

Prevention of homozygous beta-thalassemia by carrier screening and prenatal diagnosis in Sardinia.

We report here results of a 3-year pilot voluntary screening program coupled with prenatal diagnosis directed to the prospective prevention of homozygous beta-thalassemia (beta-thal) in Sardinia. The screening program took two approaches: outreach community testing and hospital testing on request after a period of sensibilization. The outreach testing was very effective as, taking into account the already known number of couples at risk with an affected proband (20), 74% of the couple at risk expected (61) on the basis of the carrier rate were identified. Less effective was the hospital testing in which half of the couples at risk expected were detected (502 with the 199 without an affected proband). After nondirective genetic counseling, approximately 85% of the couples at risk, which had a pregnancy, with no statistically significant difference between those with and those without a proband, requested prenatal testing. This figure showed a steadily increase from the beginning in 1977 to 1980. All the pregnancies (42), but two carrying homozygous fetuses, were terminated on parental request. A continuous hospital survey of thal-major admissions in the different hospitals of the counties showed a steady decline in the incidence figure at birth from 1976 (1:213) to 1978 (1:290). These results showed that even in a medium-developed, rural, Catholic population screening coupled with prenatal diagnosis can be successful in the control of a fatal, recessively inherited disorder.

Adult↗
PubMed1981

Clinical presentation of thalassemia major due to homozygous beta (0)-thalassemia.

This study concerns the clinical presentation of all thalassemia major or intermedia in children admitted to out genetics department from January 1978 to December 1979. At electrophoresis and/or globin chain synthesis analysis on column chromatography. All these patients were shown to have homozygous beta(0)-thalassemia. The clinical severity was highly variable, dependent on age at presentation and when the patient first became dependent on transfusions. On the main reasons for this variability may be associated with thalassemia 1 or alpha-thalassemia 2 which have an incidence figure of 13 % in our population and hence also in these patients. Remarkable findings of the clinical and hematological picture were: (a) early spleen enlargement and growth deficiency; (b) MCV and MCH values intermediate between normals and beta-thalassemia heterozygotes; (c) normal mean hemoglobin A2 percentage and corpuscular concentration; (d) frequently increased transferrin saturation and ferritin levels; (e) presentation at age greater than 2 with hemoglobin levels about 9 g/dl usually associated with a milder course.

Adolescent↗
PubMed1981

Globin chain synthesis analysis in obligate beta 0-thalassemia heterozygotes with isolated increase of hemoglobin A2 levels.

Globin chain synthesis analysis was carried out in 14 obligate beta 0-thalassemia heterozygotes, i.e., parents of children with thalassemia major or intermedia due to homozygous beta 0-thalassemia, with almost normal red blood cell indices and isolated increase of Hb A2 levels. alpha/beta globin chain synthesis ratios were almost balanced or slightly reduced (0.62-1.30). This finding suggests that these heterozygotes carry both alpha- and beta-thalassemia genes. However, alpha-globin structural gene mapping by restriction enzyme analysis must be carried out to confirm this explanation.

Female↗
PubMed1980

Polymorphism of DNA sequence in the beta-globin gene region. Application to prenatal diagnosis of beta 0 thalassemia in Sardinia.

We used a restriction endonuclease to analyze the beta-thalassemia gene in Sardinia. When we digested human DNA with the restriction enzyme Bam HI, the beta-globin gene split into a 5' portion contained in a fragment of DNA 1.8 kb in length and a 3' portion in a fragment 9.3 kb in length. In some subjects, a variation in the nucleotide sequence affecting the site recognized by this enzyme on the 3' side of the beta-globin gene resulted in a different fragment, 22 kb in length, which contained the 3' portion of the beta-globin gene. In Sardinians without beta-thalassemia, the frequency of the 9.3-kb fragment was 0.67, and that of the 22-kb fragment was 0.33. In contrast, all the beta 0-thalassemia genes were associated exclusively with the 9.3-kb fragment. Thus, the beta 0-thalassemia lesion in Sardinians apparently arose on a chromosome that had the 9.3-kb Bam HI fragment. This observation can be used in prenatal diagnosis of beta 0-thalassemia in Sardina, since demonstration of the 22.0-kb fragment would indicate the normal beta-globin genotype and exclude the beta 0-thalassemia lesion on that chromosome. (N Engl J Med 302:185-188, 1980).

Base Sequence↗
PubMed1980

Prenatal diagnosis of beta thalassaemia by fetal red cell enrichment with NH4-Cl-NH4HCO3 differential lysis of maternal cells.

Prenatal diagnosis with globin chain synthesis analysis on fetal red blood cells concentrated by NH4Cl-NH4HCO3 differential lysis of maternal cells (Orskov lysis) was carried out in 27 pregnancies at risk for beta thalassaemia and one at risk for sickle cell beta0 thalassaemia. The beta/gamma globin chain synthesis ratio was also determined after anti-i-differential agglutination (12 cases), in almost pure fetal samples (sic cases) and by extrapolation (one case). Differential lysis permitted the study of samples drawn by placental aspiration containing as little as 3.2% fetal red blood cells. There was no consistent difference between the beta/gamma ratios observed after differentail lysis and those determined after the use of the other approaches. A presumptive diagnosis of homozygous beta thalassaemia was made in nine cases. All but one of these pregnancies was terminated. The absence of beta chain synthesis was confirmed by the study of fetal blood after abortion in four cases with suitable samples. Of the remaining pregnancies, six proceeded to term and non-homozygous infants were delivered. The others are still in progress. No fetal loss occurred. Orskov lysis seems to be a very reliable method for prenatal diagnosis of beta chain abnormalities. Moreover it can minimize the number and duration of placental aspirations required and thus the risk to the fetus.

Erythrocyte Count↗
PubMed1980

Interaction between the glucose-6-phosphate dehydrogenase deficiency and thalassaemia genes at phenotype level.

No significant differences were observed in the mean values of Hb A2 levels and red cell indices between G6PD- and G6PD+ beta thalassaemia carriers apart from the MCV, which was significantly higher in beta thalassaemia G6PD- subjects, but still in the thalassaemia carrier range. No difference was seen between G6PD+ and G6PD- alpha thalassaemia carriers. G6PD+ beta thalassaemia carriers show a significant increase in G6PD levels expressed as activity per g of Hb and to lesser extent as activity per number of red cells x 10(9); in G6PD+ alpha thalassaemia carriers this increase is statistically significant only when the enzyme levels are expressed as activity per g of Hb. G6PD- beta thalassaemia carriers had enzyme levels higher than non-thalassaemic G6PD- subjects only when the activity is expressed per g of Hb. G6PD activity was found to be increased in G6PD+ and G6PD- Hb H disease patients.

Erythrocyte Count↗
PubMed1980

Prenatal diagnosis of beta thalassemia: experience with 133 cases and the effect of fetal blood sampling on child development.

Prenatal diagnosis was attempted in 133 pregnancies at risk for beta thalassemia (132 cases) or sickle-cell beta 0 thalassemia (1 case). Of these, 76 couples requested diagnosis because they already had children affected with homozygote beta thalassemia (72 cases) or beta+ thalassemia (4 cases). The others were probably at risk for beta 0 thalassemia since this is by far the predominant thalassemia type in Sardinia. Sufficient fetal blood for analysis was obtained by placental aspiration at 18--24 weeks gestation in 130 cases. Ten fetal losses occurred. The pregnancies were followed and no relevant complications were seen. Of the newborns delivered, 45 were followed from birth with particular attention to congenital malformation, neurological, growth, and maturity assessement. No major adverse effect of placentocentesis on child growth and development was observed. Placental samples were analyzed by globin chain synthesis analysis on carboxylmethylcellulose columns. When the placental samples contained more than 20% maternal red cells, fetal red cell enrichment was carried out by anti-i (53 cases) or anti-AB (2 cases) differential agglutination or NH4Cl-NH4HCO3 differential lysis of maternal cells (17 cases). Of the 130 cases, 32 fetuses had no beta-chain radioactivity and one had a beta/gamma ratio of 0.005. These were presumed to be homozygous and all but one were electively aborted. Absence of beta-chain radioactivity was confirmed in 10 abortuses with suitable cord blood samples. A total of 91 infants have been born and are nonhomozygous. Genotype assessment at 6 months after birth in 33 infants showed that there was only a slight overlap between the ranges of normal (0.095 +/- 0.016) and heterozygous (0.05 +/- 0.01) fetal beta/gamma globin chain synthesis ratios.

Blood Specimen Collection↗