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K Dellagi

Publications and source records attributed to K Dellagi.

At least 19 recordsLinked to original sources
PubMed2006

[Prevalence of Pneumocystis jiroveci pneumonia in Tunisian primary immunodeficient patients].

UNLABELLED: Pneumocystis Jiroveci pneumonia (PJP) is a rare opportunistic infection in immunodeficient patients in Tunisia, as well as in other Africain countries including those with a high prevalence of AIDS. In the literature, PJP has been reported in primary immunodeficiency diseases (PID) namely SCID T-B- or T-B+ or X-linked hyper-IgM syndrome. OBJECTIVE: To evaluate the prevalence of PJP in the different PID observed in Tunisia. PATIENTS AND METHODS: This retrospective study concerned 290 cases of PID confirmed by immunological investigation including the study of specific and/or non-pecific humoral and cellular immunity. The identification of P. Jiroveci in patients suspected of pneumocystosis was achieved by parasitological investigation in bronchoalveolar lavages. RESULTS: A PID associated to a parasitologically confirmed pneumocystic infection was found in 9 out of 290 patients (3%) among whom the majority (7 patients) had an HLA class II combined immunodeficiency. The latter is an autosomic recessive disease which has been reported mainly in North African families. Indeed, this population is characterized by a high rate of consanguinity. Interestingly, no PJP has been observed neither in SCID T-B- or T-B+ nor in X-linked hyper-IgM syndrome. DISCUSSION AND CONCLUSION: PJP seems to be particularly frequent in HLA class II deficiency patients, since 7 out of 22 patients with this deficiency had a PJP (31%). Due to this defect, antigen presenting cells are unable to present the antigen to T lymphocytes demonstrating the critical role of CD4+ T lymphocytes responses in the immune response to this pathogen.

Female↗
PubMed2006

FIP1L1-PDGFRA positive chronic eosinophilic leukemia in Tunisian patients.

Hypereosinophilic syndromes (HES) are a heterogenous group of rare disorders characterized by sustained and otherwise unexplained overproduction of eosinophils with organ involvement and consecutive dysfunction. Detection of the FIP1L1-PDGFRA fusion gene or the corresponding cryptic 4q12 deletion in HES supports the diagnosis of chronic eosinophilic leukemia (CEL) and provides a molecular explanation for the pathogenesis of this disorder. We screened seven Tunisian patients fulfilling the WHO criteria of HES for the presence of the FIP1L1-PDGFRA fusion gene using nested reverse transcription polymerase chain reaction on peripheral blood samples. Four of the seven patients were positive for this fusion gene. Sequence analysis revealed a substantial heterogeneity of the fusion transcripts due to the involvement of several FIP1L1 exons. All patients were male. The median age at diagnosis was 24 years (range, 18-50); one patient had a history of hypereosinophilia of more than 10 years. Two patients had clinically important and symptomatic eosinophilic endomyocardial disease with thrombotic events. Splenomegaly was constant in FIP1L1-PDGFRA positive CEL but not in the other HES patients (only 1/3).

Adolescent↗
PubMed2006

[Homozygous antithrombin type HBS deficiency; a family study].

Congenital antithrombin (AT) deficiency is the most thrombotic genetic abnormality of haemostasis. Total quantitative deficits are lethal as early as life intra-uterine. Only homozygous mutations concerning the heparin-binding site are compatible with life. We report here the case of an 18 years old patient with recurrent deep venous thrombosis of the inferior members. Haemostasis exploration shows a decreased AT activity (11%) in the presence of heparin while AT progressive activity and AT antigen are normal. Two other homozygous sisters are identified in this family study. Molecular study of AT gene show Arg47-Cys substitution, already reported in the literature with patients of different geographic origins. Treatment of patients with homozygous AT type HBS deficiency is similar that for patients with heterozygous AT deficiency; a continuous prophylactic anticoagulant treatment is always necessary and AT concentrates infusions are required in all situations needing curative heparin treatment.

Adolescent↗
PubMed2006

Approaches for the identification of potential excreted/secreted proteins of Leishmania major parasites.

Leishmania parasites are able to survive in host macrophages despite the harsh phagolysosomal vacuoles conditions. This could reflect, in part, their capacity to secrete proteins that may play an essential role in the establishment of infection and serve as targets for cellular immune responses. To characterize Leishmania major proteins excreted/secreted early after promastigote entry into the host macrophage, we have generated antibodies against culture supernatants of stationary-phase promastigotes collected 6 h after incubation in conditions that partially reproduce those prevailing in the parasitophorous vacuole. The screening of an L. major cDNA library with these antibodies led us to isolate 33 different cDNA clones that we report here. Sequence analysis revealed that the corresponding proteins could be classified in 3 groups: 9 proteins have been previously described as excreted/secreted in Leishmania and/or other species; 11 correspond to known proteins already characterized in Leishmania and/or other species although it is unknown whether they are excreted/secreted and 13 code for unknown proteins. Interestingly, the latter are transcribed as shown by RT-PCR and some of them are stage regulated. The L. major excreted/secreted proteins may constitute putative virulence factors, vaccine candidates and/or new drug targets.

Animals↗
PubMed2005

Vaccination with the divergent portion of the protein histone H2B of Leishmania protects susceptible BALB/c mice against a virulent challenge with Leishmania major.

To identify approaches for vaccination against leishmaniasis, we analyzed the protective effect of different constructions using recombinant peptides from the protein Leishmania (L.) major histone H2B. H2B sequence displays two distinct regions: an amino-terminal region divergent from mammalian H2B (27% identity) and a carboxy-terminal region highly conserved with mammalian H2B (55% identity). We tested the ability of the entire H2B protein, its divergent or conserved regions to provide protection against virulent L. major challenge. While the recombinant H2B protein adjuved with CpG induces potent cellular and antibody responses when injected to BALB/c mice, only the divergent amino-terminal region of H2B is able to confer potent protection against a virulent challenge. These findings indicate that different portions of the same parasite protein may express contrasting protective effects likely through the induction of different effector mechanisms. Due to its potent protective properties in the BALB/c mouse model, the amino-terminal region of Leishmania H2B could constitute a good vaccine candidate.

Animals↗
PubMed2005

[Type 2B and pseudo type 2B Von Willebrand disease; a report of three cases].

Increased affinity of Von Willebrand factor (VWF) for its platelet receptor GPIb-GPIX complex is responsible of an hemorrhagic disease, which is the Von Willebrand disease (VWD) type 2B when the molecular abnormality is located on the VWF, and the platelet-type 2B VWD when the mutation concern the platelet receptor. Haemostatic abnormalities in these bleeding disorders are similar; prolonged bleeding time, fluctuating thrombocytopenia, decreased factor VIII-VWF complex, and an increased response to low dose of ristocetin in platelets rich plasma. High molecular weight VWF multimers are decreased. We report here 2 cases of type 2B VWD and 1 case of platelet type 2B VWD. The distinction between these 2 diseases was established by studying platelet aggregation with weak doses of ristocetin in mixtures of washed platelets (of normal control or patient)+poor platelets plasma (normal or patient). In one case, VWD 2B was discovered late in a 49 years old man, and the factor VIIIC-VWF complex was not diminished. The distinction between these two congenital diseases is important for the treatment of bleeding manifestations which need VWF concentrates infusions in type 2B VWD and administration of platelets concentrates in pseudo type 2B VWD.

Adult↗
PubMed2005

Contrasting patterns of hepatitis C virus infection in two regions from Tunisia.

This report is a population-based study describing the pattern of hepatitis C virus (HCV) infection in two distinct regions in Tunisia. The study included a total of 11,507 individuals sampled in 1996 from both genders, all age groups, urban and rural settings belonging to 2,973 families. HCV infection was assessed by commercial enzyme immunoassay (EIA) and immunoblot assays and detection of HCV RNA by PCR. HCV genotypes and subtypes were determined by sequencing in the 5'-untranslated region (UTR) viral genomic region and the INNO-LiPA HCVII genotyping kit. Genetic relatedness between HCV strains was assessed by sequencing of a portion of the NS5B region. HCV prevalence was significantly higher in the North-Western region than in the Southern one: 1.7% versus 0.2% (P < 10(-3), chi(2) = 8,506). There was no difference in positivity according to gender or living in rural or urban settings; the only significant risk factor was advanced age. HCV prevalence among household contacts of HCV positives was not significantly higher than the prevalence in the whole study population. These results indicate a heterogeneity in the geographical distribution of HCV in Tunisia. An increased HCV transmission occurs in the North-Western region with large predominance of genotype 1b (88%) and low contribution of intrafamilial transmission.

5' Untranslated Regions↗
PubMed2005

[Association study between diabetic retinopathy and aldose reductase gene polymorphism in Tunisians].

INTRODUCTION: Aldose reductase (ALR2), the enzyme of the polyol pathway, may play an important role in the pathogenesis of diabetic microvascular complications, namely diabetic retinopathy. The study aimed to determine whether the aldose reductase gene is involved in diabetic retinopathy in the Tunisian population. MATERIAL: and methods: A case-control study was conducted in 47 type 2 diabetic patients who have diabetic retinopathy and 28 diabetic patients without diabetic retinopathy in spite of diabetes lasting for more than 5 years and over 10 years in 13 cases. We investigated the association between the (CA)n polymorphism located at 2.1 kb upstream of the transcription start site of ALR2 and diabetic retinopathy. The distribution of genotypes and alleles was compared between cases and controls by chi2 test using Epi info software. RESULTS: Genotyping of the two groups did not demonstrate any association between the alleles of this marker and diabetic retinopathy in the Tunisian population studied. DISCUSSION: An association between one of the alleles (Z - 2) of this microsatellite and diabetic retinopathy was identified in Chinese and Japanese patients with type 2 diabetes. Discordant results were obtained for the different populations studied. The lack of an association between diabetic retinopathy and ALR2 alleles indicates that the ALR2 gene is not a genetic marker of predisposition to diabetic retinopathy for type 2 diabetic patients in the Tunisian population studied.

Aldehyde Reductase↗
PubMed2005

Comparative evaluation of specific ELISA and RFFIT antibody assays in the assessment of dog immunity against rabies.

Two techniques are currently used to evaluate the humoral immune responses to rabies vaccination: ELISA, which detects binding antibodies to viral antigens and the WHO reference rapid fluorescent focus inhibition test (RFFIT), which assays in vitro virus-neutralizing antibodies. In this study, we have comparatively evaluated antibody responses of dogs reared either in an experimental kennel or living in field conditions after vaccination with a cell culture-derived rabies vaccine. In experimental conditions, both ELISA and RFFIT techniques were well correlated. However, in field conditions, they yielded discrepant results particularly in evaluating the residual rabies immunity before vaccine administration and in identifying seroconverted dogs. After rabies vaccination in field conditions, while similar antibody titres and seroconversion rates were obtained using either technique, the discrimination of a given dog according to the seroconversion threshold depended on the assay. We concluded, that whereas in experimental conditions, ELISA and RFFIT were well correlated, in field conditions ELISA yielded upper estimates. Consequently, RFFIT, although a cumbersome test, should continue to be considered as the reference rabies antibody assay technique. A seroconversion threshold of 0.5 IU/ml should be cautiously considered and a higher threshold (1 IU/ml) could be more appropriate in the evaluation of rabies immunity in the field in order to marginalize the interfering factors.

Animals↗
PubMed2005

First-line thalidomide-dexamethasone therapy in preparation for autologous stem cell transplantation in young patients (<61 years) with symptomatic multiple myeloma.

Thalidomide-dexamethasone therapy was given in patients (<61 years) with previously untreated symptomatic multiple myeloma. The aim of this study was to assess the efficacy and toxicity of this combination as first-line therapy, and to determine its effect on stem cell collection and engraftment. During first-line therapy, thalidomide and dexamethasone were administered for 75 days (200 mg/day) and 3 months, respectively. The monthly dose of dexamethasone was 20 mg/m2/day for 4 days, with cycles repeated on days 9 to 12 and 17 to 20 on the first and the third month of therapy. After first-line therapy, a collection of peripheral blood stem cells (PBSC) was performed. Between May 2003 and September 2004, 60 patients were included. On an intent-to-treat basis, the overall response (> or =partial response) rate was 74%, including 24% of patients who obtained a complete remission. Grade 3-4 toxicities consisted of infections (12%), deep-vein thrombosis (3%), constipation (5%), and neuropathy (5%). A total of 58 patients (96%) proceeded to PBSC mobilisation and yielded a median number of 8 x 10(6) CD34+ cells/kg. First-line thalidomide-dexamethasone therapy is effective and relatively well tolerated in young patients with symptomatic multiple myeloma. This combination does not affect PBSC mobilisation.

Adult↗
PubMed2005

Gamma interferon is dispensable for neopterin production in vivo.

Previous studies have indicated that neopterin is synthesized in vitro by human monocyte-derived macrophages and dendritic cells upon stimulation with gamma interferon (IFN-gamma). Neopterin production under specific conditions in vitro has also been obtained upon stimulation with IFN-alpha and/or IFN-beta. However, it is unknown if any IFN-gamma-independent neopterin synthesis is possible in vivo. In the present study we investigated the serum neopterin concentrations in patients affected by the syndrome of Mendelian susceptibility to mycobacterial disease (MSMD). Indeed, this syndrome is characterized by deeply impaired or absent IFN-gamma production or function due to severe mutations in molecules involved in IFN-gamma/interleukin-12 (IL-12)/IL-23-dependent pathway. Serum neopterin levels were measured by an enzyme-linked immunosorbent assay in 27 patients with MSMD. We found that serum neopterin levels are elevated in the complete absence of IFN-gamma activity due either to a complete deficiency of its receptor or to deleterious mutations of IL-12 or its receptor. These data clearly indicate that, as reported from in vitro studies, other stimuli are able to induce neopterin synthesis in vivo. Consequently, neopterin cannot be used as means of diagnosis of MSMD due to IFN-gamma-, IL-12-, and IL-23-dependent pathway defects.

Adolescent↗
PubMed2004

Involvement of chemokines and Th1 cytokines in the pathogenesis of mucocutaneous lesions of Behçet's disease.

OBJECTIVE: To investigate a possible pathogenic role of cytokines in Behçet's disease (BD) by focusing on the analysis of cytokine gene expression within mucocutaneous BD lesions. METHODS: The study group comprised 20 patients with active BD. In this group, a set of chemokines as well as Th1 and Th2 cytokines in biopsy specimens obtained from oral and genital ulcers, pseudofolliculitis lesions, and lesions at the site of pathergy testing were studied using real-time quantitative reverse transcriptase-polymerase chain reaction. RESULTS: We observed important increases in the expression of interleukin-8 (IL-8) ( approximately 700-fold), monocyte chemoattractant protein 1 ( approximately 65-fold), interferon-gamma ( approximately 71-fold), and IL-12 ( approximately 69-fold) messenger RNA in BD lesions compared with normal skin. Except for IL-10 ( approximately 75-fold increase), Th2 cytokines (i.e., IL-4 and IL-13) were absent. CONCLUSION: Our data suggest a direct role of Th1 lymphocytes in the pathogenesis of mucocutaneous BD lesions.

Adult↗
PubMed2003

Genotypes of hepatitis C virus circulating in Tunisia.

Hepatitis C virus (HCV) isolates from 93 patients living in Tunisia, including 16 haemophiliacs, were genotyped by INNO LiPA and partial sequencing of the 5' untranslated region of the viral genome. In non-haemophiliacs, subtype 1b was largely predominant (79%), types 1a, 2a, 2b, 3a and 4a occurred much less frequently at 5, 7, 3, 3 and 1% of cases, respectively. In the group of haemophiliacs, a co-dominance between subtypes 1a and 1b was noticed (38%). Type distribution of HCV in Tunisia differs from that reported in other countries of the Mediterranean and Middle East regions. Genotyping results in respect of clinical status, age, and genotyping methods, are discussed.

Adolescent↗
PubMed2003

A novel missense mutation in the gene encoding SLURP-1 in patients with Mal de Meleda from northern Tunisia.

BACKGROUND: Mal de Meleda (MDM) is a rare autosomal recessive skin disorder which belongs to the clinically and genetically heterogeneous group of palmoplantar keratodermas (PPK). Clinically, MDM is characterized by erythema and hyperkeratosis of the palms and soles with sharp demarcation that appears soon after birth and progressively extends to the dorsal surface of the hands and feet. OBJECTIVES: Except for the molecular study reported in Algerian families, MDM has not yet been investigated in the Maghrebian population, characterized by its heterogeneous ethnic background and a high rate of consanguinity. In this study we report genetic and molecular investigations of eight unrelated consanguineous Tunisian families including 17 affected individuals. METHODS: Eight large consanguineous MDM families who originated from cities of northern Tunisia, with a total of 17 patients and 22 unaffected family members were investigated. Families were genotyped with the following microsatellite markers: CNG003, D8S1751 and D8S1836. Mutation analyses were performed in affected patients, in both parents and in unaffected individuals. Linkage analysis was also performed. RESULTS: All the clinical features of MDM were constantly present. Nevertheless variable severity was noted among patients. Histological details were recorded. The haplotype analysis of markers CNG003, D8S1751 and D8S1836 revealed that all affected offspring were homozygous by descent for the three polymorphic markers. The maximum lod score value, 3.22, confirmed the evidence for linkage to the ARS gene. Three haplotypes were observed, and the findings suggest that at least three different mutations within the ARS gene segregate with these haplotypes. Three different mutations were identified, the 82delT mutation previously described and two novel missense mutations. CONCLUSIONS: The results suggest that the ARS gene is likely to be responsible for MDM in the eight Tunisian families. The clinical variability in the expression of PPK in MDM Tunisian patients might be accounted for by the intervention of modifier genes influencing the MDM phenotype.

Antigens, Ly↗