[Hemoglobinopathies in Nefza: a model of health intervention].
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Adolescent↗
Biomedical subjects
R Kastally
Publications and source records attributed to R Kastally.
Etiology of acute sporadic hepatitis in adults in Senegal and Tunisia.
Markers for acute hepatitis A, B, C and E virus infections were examined in the sera of 72 patients suffering from acute hepatitis in Senegal and Tunisia. Hepatitis B was responsible for 36% and hepatitis C for 21% of the cases. Acute hepatitis A was not diagnosed. HEV infection was not observed in Senegal and represents only 4% of the acute hepatitis cases in Tunisia.
Acute Disease↗
[Association of heterozygote drepanocytosis and G6PD deficiency: apropos of a case].
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Child↗
Familial clustering of hepatitis B virus infections and prevention of perinatal transmission by immunization with a reduced number of doses in an area of intermediate endemicity (Tunisia).
Hepatitis B surface antigen (HBsAg) was detected in 3.3% of 7162 pregnant Tunisian women tested and HBeAg in 9.6% of the HBsAg-positive mothers. Family members of 46 of these HBsAg-positive mothers (33 husbands and 61 children aged 1-6 years) were investigated for the presence of HBV markers. HBsAg was detected in 21% of the children and 18% of the husbands. Fifty children born to HBsAg-positive mothers received hepatitis B vaccine at birth, at the age of 2-3 months and at the age of 9 months. After immunization, anti-HBs were detected in 92% of them with an anti-HBs geometric mean titre of 415 mIU ml-1. Compared with the HBsAg carrier state in older siblings, the protective efficacy was estimated to be 60%. It was 100% for infants born to HBeAg-negative mothers, but only 31% for those born to HBeAg-positive mothers. For a better efficacy, the schedule of the EPI needs to be modified to include an immunization session at 1 month of age.
Adult↗
High risk genotypes for celiac disease.
It is known that celiac disease is strongly associated with an HLA class II component and that most patients carry the dimer DQA1*0501, DQB1*0201. We show in this study that the risk for a carrier of this heterodimer is independent from the number of possible heterodimers, from whether DQA1*0501 and DQB1*0201 are in cis or trans position and from the number of DQA1*0501 (one or two) but strongly depends on the number of DQB1*0201. In the Tunisian population we studied, the risk of developing celiac disease is estimated to be 6.8 times greater for those having a double dose of DQB1*0201 than for other dimer carriers. We replicated this result in published data of four other populations (Italy, Czekoslovakia, United Kingdom, Norway).
Adolescent↗
Low expression allele alpha LELY of red cell spectrin is associated with mutations in exon 40 (alpha V/41 polymorphism) and intron 45 and with partial skipping of exon 46.
The alpha V/41 polymorphism of erythroid alpha-spectrin has been characterized initially by an increased susceptibility to proteolysis of the alpha IV-alpha V domain junction (Alloisio N., L. Morlé, J. Maréchal, A.-F. Roux, M.-T. Ducluzeau, D. Guetarni, B. Pothier, F. Baklouti, A. Ghanem, R. Kastally, et al. 1991. J. Clin. Invest. 87:2169-2177). Until now, it has been found associated invariably with a low expression level of the corresponding alpha chain. Among 61 chromosomes investigated in French and North African individuals or kindreds, we observed 19 chromosomes with the alpha V/41 polymorphism. With no single exception, the latter displayed a point mutation in exon 40 (Leu-->Val; CTA-->GTA) at position alpha 1857. According to the triple helical model of spectrin structure, this change accounts for the peptide maps' abnormalities. Sequencing the entire alpha V domain cDNA disclosed, in addition, a partial skipping of exon 46. At the gene level, a substitution (C-->T) was evidenced at nucleotide -12 of intron 45. This mutation appeared linked to the exon 40 mutation in 17 chromosomes, again with no single exception, among 53 examined chromosomes. We hypothesized that the lack of exon 46 would hamper the nucleation process and eventually account for the low expression feature. The present doubly mutated allele was renamed allele alpha LELY (low expression, Lyon).
Alleles↗
Spectrin Jendouba: an alpha II/31 spectrin variant that is associated with elliptocytosis and carries a mutation distant from the dimer self-association site.
Spectrin Jendouba (alpha II/31) was found in a Tunisian family. In the heterozygous state, it is associated with asymptomatic elliptocytosis and a minimal defect in spectrin dimer self-association. On partial digestion of spectrin with trypsin, an abnormal cleavage appeared following Lys 788. Peptide and DNA sequencing indicated that the responsible mutation is alpha 791 Asp----Glu (GAC----GAA). As in most alpha-spectrin variants associated with elliptocytosis, the change alters helix 3 of the proposed triple helical model of spectrin structure. Modified helix 3 in repeat alpha 8 is the most distant from the N-terminus of alpha-spectrin in known variants associated with elliptocytosis.
Alleles↗
Elliptocytogenic alpha I/36 spectrin Sfax lacks nine amino acids in helix 3 of repeat 4. Evidence for the activation of a cryptic 5'-splice site in exon 8 of spectrin alpha-gene.
Elliptocytogenic alpha I/36 spectrin Sfax is a new variant found in a Tunisian family. The alpha I/36 allele yielded a clinically manifest picture only when occurring in trans to a recently identified, low expression level polymorphism referred to as the alpha V/41 allele. Spectrin dimers were slightly increased in 4 degrees C extracts. On peptide maps, the alpha I domain split into two abnormal fragments of 36 and 33 Kd. The mutated alpha-chain represented 20% and 44% of total alpha-chain in alpha/alpha I/36 and alpha V/41/alpha I/36 heterozygotes, respectively. Peptide sequencing showed that the 36-Kd fragment started at Ala 357 and displayed a deletion extending from amino acids 363 to 371. The corresponding 27-nucleotide deletion was found in alpha-spectrin mRNA. However, exon 8 of spectrin alpha-gene failed to disclose this deletion. Instead, an A to G substitution appeared in position 3 of codon 362, leading to the occurrence of the critical GU dinucleotide within a cryptic 5'-splice site surrounding codon 362. This event would account for the splicing out of codons 363 to 371. The reading frame was preserved and even amino acid 362 (AGG, Arg) remained unaltered. As in most spectrin alpha-chain elliptocytogenic variants, the change involved a helix 3. This is the first elliptocytogenic mutation recorded in repeat alpha 4.
Adult↗
Hepatitis C core antibody detection in acute hepatitis and cirrhosis patients from Tunisia.
The detection of anti-Hepatitis C virus (HCV) Core antibodies is an important addition to HCV antibody testing. In this study it appears to be more specific than the first generation HCV tests and in combination with the detection of anti-C33c antibodies, it is possibly more sensitive. In Tunisia hepatitis C virus is implicated by the presence of anti-Core antibodies in only 8% of the adult cases of acute hepatitis as opposed to 60% for Hepatitis B virus (HBV) and 4% for Hepatitis A virus (HAV). In contrast to the low prevalence of HCV infection among acute hepatitis cases, HCV infection is implicated in 35% of the cirrhosis cases. These results stress the potential importance of HCV infection in the development of cirrhosis which is a relatively common disease in North Africa.
Enzyme-Linked Immunosorbent Assay↗
Occurrence of the alpha I 22 Arg----His (CGT----CAT) spectrin mutation in Tunisia: potential association with severe elliptopoikilocytosis.
A category of spectrin alpha I domain variants are manifested by the increase of the alpha I 74 kDa fragment at the expense of the parent 80 kDa fragment following partial tryptic digestion. We describe a particular case of alpha I/74 abnormality in a Tunisian family. The propositus was severely ill and had an elliptopoikilocytosis. To the contrary, his father, who carried the same alpha I/74 variant, displayed no clinical signs and a few elliptocytes. The increase of the alpha I 74 kDa fragment was more pronounced in the propositus than in his father. Unexpectedly, the spectrin content was reduced to similar (and limited) extents in both of them, and the father displayed nearly as pronounced an increase of the spectrin dimer percentage as the propositus following low ionic strength extraction. In vitro spectrin dimer reconstitution experiments indicated that the primary mutation was located in the alpha-chain itself (not in the beta-chain as is the case in some alpha I/74 mutants). Following polymerase chain reaction (PCR) amplification, cloning and sequencing of exon 2 of spectrin alpha-gene in the father, we found the G----A substitution at position 2 of codon 22 (CGT----CAT; Arg----His). This mutation has been recently discovered in a family of French descent. Dot blot hybridization confirmed that the substitution was transmitted with the alpha I/74 abnormality. As previously shown, the enhancement of its expression level in the propositus, with respect to the father, was accounted for by the presence of a factor carried by the alpha-spectrin allele in trans and transmitted by the mother.
Adult↗
Sp alpha V/41: a common spectrin polymorphism at the alpha IV-alpha V domain junction. Relevance to the expression level of hereditary elliptocytosis due to alpha-spectrin variants located in trans.
Spectrin alpha-chain mutants associated with hereditary elliptocytosis are highly variable in their level of expression. It has been assumed that the degree of elliptocytosis can be increased when the spectrin alpha chain, encoded by the alpha gene in trans to the variant, is expressed at a low level. We now provide strong evidence for the existence of low-level expression of spectrin alpha chains. This condition is referred to as the alpha V/41 polymorphism. It has been observed in 15 different families or individuals of French, North African, and African ancestry in which seven distinct elliptocytogenic alpha-spectrin variants were co-inherited. Whenever the alpha V/41 polymorphism was present, the severity of the biochemical, morphological, and, sometimes, the clinical phenotype of elliptocytosis was increased. The alpha V/41 polymorphism was also frequently encountered among 36 unrelated control subjects in the heterozygous or homozygous states, and was entirely asymptomatic in both cases. The main biochemical feature was an increased susceptibility to proteolysis of the alpha IV-alpha V domain junction. Alteration of the facing beta IV domain of spectrin was demonstrated by in vitro spectrin dimer reconstitution experiments. It appears that the alpha V/41 polymorphism is often required for alpha-spectrin elliptocytogenic variants to become manifest in the heterozygous state. Thus, alpha-spectrin-related elliptocytosis may be viewed as a bifactorial condition.
Electrophoresis, Gel, Two-Dimensional↗
Spectrin Tunis (Sp alpha I/78), an elliptocytogenic variant, is due to the CGG----TGG codon change (Arg----Trp) at position 35 of the alpha I domain.
Spectrin Tunis (Sp alpha I/78) is an alpha l domain variant that causes asymptomatic elliptocytosis in the heterozygote state. It is manifested by a reduction of spectrin dimer self-association and by the development of a major 78-Kd fragment at the expense of the alpha l 80-Kd fragment upon spectrin-limited digestion. Amino acid sequence analysis, following peptide transfer onto Immobilon membranes, showed that the 78-Kd fragment results from a sensitized cleavage after lysyl residue 10. Using a 13.5-kb genomic alpha-spectrin probe and the Xbal, Pvull, and Mspl polymorphic sites detected with this probe, we concluded that spectrin Tunis is associated with the + - + haplotype (in the above order). Twenty mer oligonucleotides, complementary to genomic segments from introns 2 and 3, respectively, were synthesized. We then performed DNA amplification and sequencing. In the two investigated carriers of spectrin Tunis, we found the C----T base substitution of the codon corresponding to position 35 of the alpha l domain (CGG----TGG; Arg----Trp). The mutation lies in the last part of an alpha helix that extends from residues 9 to 44 of partial repeat alpha 1' and is comparable with helix 3 of full repeats 1 to 5. The modified proteolytic site, located 25 amino acid residues upstream, occurs at the beginning of the helix.
Amino Acid Sequence↗
High interferon titer and defective NK-cell activity in the circulation of nasopharyngeal carcinoma patients.
The interferon (IFN) activity of sera from 19 patients with nasopharyngeal carcinoma (NPC) was determined by the plaque-reduction assay with vesicular stomatitis virus (VSV) in HeLa cells and compared to that of sera from matched healthy controls. High titers of interferon were detected in the sera of the NPC patients with a geometric mean titer (GMT) of 43 +/- 25 U/ml. The interferon activity of the patients' sera was acid- and heat-labile (pH = 2 and 56 degrees C for 1 hr) and could be neutralized by a goat antiserum to human IFN-gamma. Interferon titers of the patients, in contrast, to normal controls, were not correlated with natural killer (NK) activity which was abnormally low in the NPC patients. On the other hand, a high percentage of circulating cells co-expressing the LGL marker (HNK-I) and the OKT8 antigen was detected in parallel with high IFN levels in NPC patients.
Aged↗
Hemoglobin Athens-Georgia [alpha 2 beta 2 40(C6)Arg----Lys] in association with beta 0-thalassemia in Tunisia.
We describe an Hb Athens-Georgia (Hb A-Ga)/beta 0-thalassemia compound heterozygosity, found in a Tunisian patient. Oxygen binding studies of red cell suspensions of this patient, containing approximately 95% Hb A-Ga, revealed an almost normal oxygen affinity. Nevertheless, dilute solutions of Hb A-Ga showed an increased overall oxygen affinity and decreased heme-heme interaction. This could be explained by a tetrameric hemoglobin with normal oxygen binding properties but with increased dissociation into monomers or dimers, as a consequence of a structural abnormality within the alpha 1 beta 2 interface. Such an interpretation would explain the increased oxygen affinity reported in previous studies performed on heterozygous Hb A/Hb A-Ga patients.
Hemoglobins, Abnormal↗
Incidence of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Tunisian populations.
Screening for glucose-6-phosphate dehydrogenase (G6PD) deficiency was performed on male students originating from several towns in Tunisia. Three hundred and twenty-five assays were made, allowing calculation of the mean value and standard deviation of G6PD (6.32 +/- 0.72 U/g Hb), the incidence of the deficiency (1.84%) and its geographic distribution in Tunisia. G6PD electrophoresis in 54 subjects showed marked predominance of the B+ type (96.2%) compared with the A+ type (1.96%). Three deficient subjects displayed an electrophotetic mobility identical to that of the A+ type of G6PD.
Adult↗
Hb Tunis [alpha 2 beta 2 124 (H2)Pro----Ser], a new beta chain variant identified by HPLC.
During a routine hematological investigation of a child from Tunis, a silent hemoglobin variant was discovered by isoelectric-focusing. This variant was not detectable by conventional electrophoretic methods, had normal stability, expression, and oxygen affinity, and did not produce any clinical symptoms. This new variant beta 124(H2)Pro----Ser was named Hb Tunis.
Amino Acids↗
First observation of Hb Montgomery [alpha 48(CD6)Leu----Arg] in Tunisia.
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Adult↗
Spectrin Tunis (alpha I/78): a new alpha I variant that causes asymptomatic hereditary elliptocytosis in the heterozygous state.
Spectrin Tunis (alpha 1/78) was found in the heterozygous state in a young white North-African man and his mother. Both of them presented with mild elliptocytosis. Using one-dimensional electrophoresis, a sharp 78 kd fragment was present with a reciprocal decrease of the alpha I 80 kd domain. Kinetic analysis unambiguously confirmed that the 78 kd fragment developed at the expense of the alpha I 80 domain. The alpha I 74 kd peptide was not flanked with a peptide lacking a 2 kd fragment. From this fact, it could be inferred that the site for additional proteolysis is located upstream from arginyl residue 39 and, more precisely, should lie 10 to 20 amino-acid residues (-2 kd) from the alpha-chain N-terminus. The percentage of spectrin dimers in 4 degrees C extracts was high (over 40%), contrasting with the absence of clinical symptoms related to elliptocytosis. This is the first mutation responsible for elliptocytosis found in Tunisia.
Adult↗