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Biomedical subjects

S T Saad

Publications and source records attributed to S T Saad.

At least 73 records · Page 4Linked to original sources
PubMed1995

Molecular identification of hereditary persistence of fetal hemoglobin type 2 (HPFH type 2) in patients from Brazil.

The HPFH deletion type 2 was first described in a patient from Ghana and is characterized by a large deletion of approximately 105 kb extension. We report here the results obtained in studying a black Brazilian patient who presented an association of beta-thalassemia and HPFH type 2, using a PCR strategy for detection of the breakpoint region. This procedure allows a rapid molecular identification of this condition and is a reliable procedure for screening patients with a hematological picture of HPFH deletion types.

Adult↗
PubMed1995

Enalapril reduces the albuminuria of patients with sickle cell disease.

PURPOSE: To evaluate the effects of enalapril, an angiotensin-converting enzyme inhibitor, on albuminuria associated with sickle cell anemia. PATIENTS AND METHODS: Two males and 6 females, mean age 22.8 +/- 5.5 years, with sickle cell anemia and albuminuria, received enalapril for 6 months. Before entry into the study, all had a urinary albumin concentration above 30 mg/L as determined by radioimmunoassay documented on three separate occasions at intervals of 15 to 30 days. Samples were collected before 10 AM after an oral water load of 10 mL/kg. RESULTS: Enalapril reduced 6 patients' pretreatment hyperalbuminuria to normal. One patient whose levels did not reach normal values experienced a reduction of 70%. Fractional excretion of sodium, potassium, and lithium did not change during the treatment. Mean arterial pressure decreased by 8.6 +/- 0.42 mm Hg. Two years after enalapril was discontinued, there were no changes in sodium, potassium, or creatinine levels of 7 patients who had received enalapril or in their mean arterial pressures. Urinary albumin concentration increased relative to pretreatment levels in 2 individuals, returned to pretreatment levels in 2, and remained below 30 mg/L in 2. CONCLUSION: Our results demonstrate that enalapril reduces albuminuria in patients with sickle cell anemia. After discontinuation of the drug, however, the albuminuria may increase to pretreatment levels or higher. Whether the reduction in urinary albumin concentration by angiotensin-converting enzyme inhibitors can delay the development of progressive renal failure in sickle cell anemia patients remains to be established.

Adolescent↗
PubMed1994

Red cell membrane protein abnormalities in hereditary spherocytosis in Brazil.

We studied 14 kindred and nine unrelated patients from southeastern Brazil with the typical form of hereditary spherocytosis. Diagnosis was made on the basis of clinical features, presence of spherocytes on the peripheral blood smears and an abnormal osmotic fragility test. By densitometric tracing of SDS-PAGE stained by Coomassie blue, we detected isolated deficiency of spectrin in 39% of our patients, combined spectrin and ankyrin deficiency in 13%, and deficiency of band 3 in 13%. One of our patients presented ankyrin deficiency without spectrin reduction. Our data suggest that, despite ethnic differences among the Brazilian and European or North-American populations, these biochemical abnormalities in HS patients may be similar.

Anion Exchange Protein 1, Erythrocyte↗
PubMed1994

Hb Lepore Baltimore (delta 50Ser beta 86Ala) identified by DNA analysis in a Brazilian family.

Genomic DNA from two Brazilian hemoglobin (Hb) Lepore heterozygotes of Italian ancestry have been studied in order to identify the Hb Lepore type and to sequence the breakpoint region. The two genes were sequenced after PCR amplification and had the delta globin sequence up to exon 2 codon 68 while the first specific base for the beta globin gene was at codon 86 of the second exon; between the two ends, they had 51 base pairs in common with the delta and beta globin genes. These data indicate that the mutation was of the Hb Lepore Baltimore type. The Lepore chromosome haplotype was different from that previously described in members of a Spanish family with Hb Lepore Baltimore. These data suggest that independent mutations have given rise to Hb Lepore Baltimore in different regions of the world.

Anemia↗
PubMed1994

Duplication of 10 nucleotides in the erythroid band 3 (AE1) gene in a kindred with hereditary spherocytosis and band 3 protein deficiency (band 3PRAGUE).

We describe a duplication of 10 nucleotides (2,455-2,464) in the band 3 gene in a kindred with autosomal dominant hereditary spherocytosis and a partial deficiency of the band 3 protein that is reflected by decreased rate of transmembrane sulfate flux and decreased density of intramembrane particles. The mutant allele potentially encodes an abnormal band 3 protein with a 3.5-kD COOH-terminal truncation; however, we did not detect the mutant protein in the membrane of mature red blood cells. Since the mRNA levels for the mutant and normal alleles are similar and since the band 3 content is the same in the light and dense red cell fractions, we conclude that the mutant band 3 is either not inserted into the plasma membrane or lost from the membrane prior to the release of red blood cells into circulation. We further show that the decrease in band 3 content principally involves the dimeric laterally and rotationally mobile fraction of the band 3 protein, while the laterally immobile and rotationally restricted band 3 fraction is left essentially intact. We propose that the decreased density of intramembrane particles decreases the stability of the membrane lipid bilayer and causes release of lipid microvesicles that leads to surface area deficiency and spherocytosis.

Anion Exchange Protein 1, Erythrocyte↗
PubMed1994

A novel mobile element inserted in the alpha spectrin gene: spectrin dayton. A truncated alpha spectrin associated with hereditary elliptocytosis.

Nonviral retrotransposons, retropseudogenes, and short interspersed nuclear elements (SINEs) are mobile DNA segments capable of transposition to new genomic locations, where they may alter gene expression. De novo integration into specific genes has been described in both germ and somatic cells. We report a family with hereditary elliptocytosis and pyropoikilocytosis associated with a truncated alpha-spectrin protein. We present the biochemical characteristics of this abnormal protein and show that the alpha-spectrin gene is disrupted by a mobile element resulting in exon skipping. This element causes duplication of the insertion site and is terminated by a long poly-A tail downstream of multiple consensus polyadenylation signals. Southern blot analysis of human genomic DNA, using this element as probe, reveals one to three copies per individual. This element has no homology to any previously reported sequence and therefore appears to be a member of a novel family of mobile elements.

Base Sequence↗
PubMed1994

The role of bone marrow study in diagnosis and prognosis of myelodysplastic syndrome.

In this study, cases of myelodysplasia diagnosed in a brazilian population are reported. Some differences such as a higher number of cases of hypocellular bone marrow (45.6%) were observed. There was no significant difference between patients that developed acute leukemia or not, when some bone marrow parameters such as cellularity, abnormality in reticulin fibers presence of atypically located immature precursors (ALIP), quantitative and qualitative changes of erythroblastic, granulocytic and megakaryocitic series were compared. There was no correlation either between ALIP and excess of blasts in cytology, or between FAB classification and bone marrow histology. Patients with hypocellular marrow presented lower frequency of atypic megakaryocitc than patients with normo or hypercellular bone marrow and a shorter, although not statistically significant survival. The survival of patients with ALIP was significantly lower than of those without ALIP. Cases of RAEB had a worse prognosis when compared to RA. Bone marrow histology had an important role in the differential diagnosis between MDS with hypoplastic marrow and aplastic anemia.

Adult↗
PubMed1993

Rapid identification of beta-globin structural mutations by sequencing the mRNA from peripheral blood reticulocytes.

A simple and rapid method for the molecular detection of beta-globin structural mutations is described using a reverse transcription-polymerase chain reaction of reticulocyte mRNA and direct sequencing of the product. The amplified segment (employing a sense primer 5'-ATTTGCTTCTGACACAACTGT-3', located at position + 1 with respect to the Cap site and an antisense primer 5'-TCCAGATGCTCAAGGCCCTTC-3', located at position + 1772 with respect to the Cap site) encompasses the cDNA sequence including the three globin exons. Employing this method we were able to characterize two hemoglobin structural variants: Hb S (beta 6 (A3) Glu-Val: GAG-GTG) and Hb Porto Alegre (beta 9 (A6) Ser-Cys: TCT-TGT). The approach described in this paper should be very useful to detect hemoglobin structural variants because the RNA extraction is simple, rapid and does not require cesium chloride, guanidinium and proteinase K. In addition, the direct sequencing of the RT-PCR product permits the screening of the entire globin genes with only two reactions.

Base Sequence↗
PubMed1992

Glucose-6-phosphate dehydrogenase deficiency and sickle cell disease in Brazil.

The frequency of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency was determined in 54 male patients with sickle cell diseases: 31 sickle cell anemia (SS), 14 sickle cell hemoglobinopathy (SC) and 9 HbS/beta-thalassemia (S/B-thal) by a combination of quantitative assay, fluorescent spot test and electrophoresis. Of the 54 patients tested, 7 were found to be G-6-PD deficient (G-6-PD-) (3 SS, 3 SC and 1 S/B-thal) and 47 G-6-PD normal (G-6-PD+) (6 G-6-PD A and 41 G-6-PD B). All the deficient patients were G-6-PD A-. The frequency of G-6-PD deficiency did not differ significantly from that observed in the general population. Compared to patients who were not G-6-PD-, there were no significant differences in the hemoglobin concentration and reticulocyte count in patients with sickle cell diseases who were G-6-PD-.

Adolescent↗
PubMed1992

Normal cortisol secretion in sickle cell anemia.

In the present work, 14 sickle cell anemia patients and 16 normal controls were submitted to rapid ACTH stimulation test for basal cortisol determination. No significant differences were observed between the two groups for the basal and stimulated cortisol levels or for the increment at 30, 50 and 120 min. after infusion. The results obtained for the basal cortisol were in disaccordance with a previous report; however, we used a sensitive test to detect precocious involvement of the adrenal glands. This suggests that in sickle cell anemia there is not hypocortisolism. The adrenal gland is vascularized by several arteries and so the sickling phenomenon may be unusual in the adrenal cortex.

Adolescent↗
PubMed1991

Insulin secretion in patients deficient in glucose-6-phosphate dehydrogenase.

Intravenous (IVGTT) and oral glucose tolerance tests (OGTT) were carried out in 12 men with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and in 11 normal men. The race, the mean age and body mass index were similar in the G-6-PD deficient and in the normal men. No significant differences were demonstrated between mean plasma glucose levels in the G-6-PD deficient subjects and those in the normal men during IVGTT and OGTT. In contrast the insulin levels were significantly lower for the G-6-PD deficient subjects as compared to the controls at 30 minutes (P less than 0.04) in the OGTT and at 1 min (P less than 0.001), 3 min (P less than 0.001), 5 min (P less than 0.001) and 10 minutes (P less than 0.002) in the IVGTT. All indexes of first phase insulin release were also significantly (P less than 0.001) lower in G-6-PD deficient men. These results emphasize the metabolic importance of G-6-PD in the process of glucose induced insulin release.

Adult↗
PubMed1991

Reduced cortisol secretion in patients with iron deficiency.

The iron-containing protein cytochrome P-450 is present in high concentration in the adrenal cortex and is involved in the synthesis of corticosterone. This study was designed to determine the cortisol response to adrenocorticotropin (ACTH) in patients with severe iron deficiency. Eleven patients with iron deficiency and 15 normal controls were studied. Fasting blood samples were taken from all the subjects before and 30, 60 and 120 min after infusion of 25 units of ACTH for plasma cortisol determination. Six patients had blood samples collected at night, too. The same test was performed in 6 patients with iron deficiency, 7 days after therapy with 800 mg of ferrous sulfate. No significant differences were observed between patients and controls for the baseline cortisol values. The cortisol secretion and the increment at 30, 60 and 120 min after ACTH infusion were significantly lower in patients than in controls, either before or after ferrous sulfate therapy. There were no significant differences between baseline and stimulated cortisol values in patients before and after 7 days of ferrous sulfate therapy. There was no change in cortisol secretion rhythm in patients with iron deficiency (cortisol level at night = 5.1 +/- 4.3 micrograms/dl). In conclusion, the results of the present study showed that, in patients with severe iron deficiency, the cortisol secretion after ACTH stimulation was decreased.

Adrenocorticotropic Hormone↗
PubMed1991

Cortisol levels in glucose-6-phosphate dehydrogenase deficiency.

The aim of the present study was to investigate cortisol levels under basal conditions and in response to ACTH stimulation in male patients with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. The study included 14 male controls and 12 patients with G-6-PD deficiency matched for age and race. Fasting blood samples were taken from all the subjects at rest, and 30, 60 and 120 min after the infusion of 0.25 mg of corticotropin for cortisol determination. The mean cortisol levels observed in the first hour after ACTH stimulation in the G-6-PD-deficient patients were significantly (p = 0.03) lower than in the control group. No significant differences were observed between patients and controls at rest, and in the second hour after stimulation. These data suggest that, in the adrenals, G-6-PD plays a role in the initial phase of cortisol production. However, 1 h after ACTH stimulation, G-6-PD probably is no longer rate limiting in the production of cortisol.

Adrenocorticotropic Hormone↗