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Biomedical subjects

K Dellagi

Publications and source records attributed to K Dellagi.

At least 55 records · Page 3Linked to original sources
PubMed1999

[Chronic septic granulomatous disease. 14 cases].

OBJECTIVES: Chronic granulomatous disease (CGD) is a rare inherited immunodeficiency. Affected children are mostly boys. The most common clinical features are recurrent bacterial and fungal infections starting at early childhood. We report 14 cases, including 5 girls, of CGD in Tunisian children. PATIENTS AND METHODS: This retrospective study concerned 14 clinical observations of CGD recorded between April 1988 and December 1998. The diagnosis was established upon determination of a defective respiratory burst in the patients' neutrophils at the tetrazolium nitroblue test (NBT). In 4 cases, the diagnosis was also confirmed by chemiluminescence assay. RESULTS: The patients (9 boys and 5 girls) belonged to 12 families, 75% of which were consanguineous. In 6 families, there had been several deaths in early childhood. The mean age at onset of clinical signs was 6.8 months (7 days to 24 months). Clinical signs included lung (10 cases), nodal (8 cases), skin (7 cases), and intestinal (7 cases) infections. Seven patients developed invasive pulmonary aspergillosis with parietal extension in 4 cases. Salmonella and Staphylococcus infections were rare in our series. Six children (42.8%) including 2 girls, died. Aspergillosis was fatal in 4 cases. CONCLUSION: Recurrent infections are the main clinical fetus of chronic granulomatous disease. Prognosis has been improved by the use of prophylactic antibiotics. Early diagnosis of the disease is crucial.

Aspergillosis↗
PubMed1999

A model to study the effects of a viral inactivator (beta-propiolactone) on DNA ligation and gene expression in E. coli and Cos cells.

An experimental model to study the effects of viral inactivators on the biological properties of DNA was developed. Beta-propiolactone (betaPL) was used in this model and its effects on ligation, transfer and gene expression of naked DNA were assessed. Evidence that betaPL impairs these two major DNA functions are presented. The amounts of betaPL that alter or abolish gene expression and prevent DNA cohesive ends ligation were determined. Based on these observations, it was concluded that this experimental approach could be used to study the effects on the biological properties of DNA of other inactivators used in vaccine preparations.

Animals↗
PubMed1999

Leishmanin skin test lymphoproliferative responses and cytokine production after symptomatic or asymptomatic Leishmania major infection in Tunisia.

Resistance to Leishmania parasite infection requires the development of a cellular immune response that activates macrophage leishmanicidal activity. In this study we have investigated the lymphoproliferative responses and in vitro cytokine production of peripheral blood mononuclear cells (PBMC) from individuals living in an endemic area for L. major infection in Tunisia. The results were compared with the DTH reaction of the leishmanin skin test (LST). Sixty-seven individuals were included in the study: 22 persons (age range 9-60 years) who developed, 2 years before the present study, a parasitologically confirmed localized cutaneous leishmaniasis (LCL) that healed spontaneously, and 45 individuals (age range 18-20 years) born and living in the same area, with no previous history of LCL. LST was positive (skin induration > or = 5 mm) in 20/22 cured cases of LCL and in 75% of healthy individuals without history of LCL. LST+ individuals expressed vigorous Leishmania-specific lymphoproliferative responses associated with in vitro production of interferon-gamma (IFN-gamma) but not IL-4. Interestingly, IL-10 was detected in parallel with the highest levels of IFN-gamma in PBMC supernatants from 3/20 cured LCL and 8/25 individuals without history of LCL. Our results showed a 98% concordance between the DTH reaction assessed by LST and the in vitro proliferative assay induced by soluble leishmanial antigens. Moreover, proliferative assays as well as cytokine analysis did not show any significant difference of the immune memory to parasite antigens developed by patients who had overt cutaneous leishmaniasis and those who had apparently asymptomatic infection.

Adolescent↗
PubMed1999

Depletion of peritoneal CD5+ B cells has no effect on the course of Leishmania major infection in susceptible and resistant mice.

The mouse peritoneal cavity contains a unique self-renewing population of B cells (B-1) derived from fetal liver precursors and mainly producing polyreactive antibodies. Since B-1 cells are a potential source of IL-10, it has been suggested that these cells may contribute to the susceptibility of BALB/c mice to Leishmania major infection by skewing the T helper cell network towards a Th2 phenotype. Accordingly, L. major infection of B cell-defective BALB/c Xid mice (lacking B-1 cells) induces less severe disease compared with controls. However, in addition to the lack of B-1 cells, the Xid immune deficiency is characterized by high endogenous interferon-gamma (IFN-gamma) production. In the present study, the role of B-1 cells during L. major infection was investigated in mice experimentally depleted of peritoneal B-1 cells. Six weeks old C57Bl/6 and BALB/c mice were lethally irradiated and reconstituted with autologous bone marrow which allows systemic depletion of B-1 cells. Untreated BALB/c, C57Bl/6 as well as BALB/c Xid mice were used as controls. After reconstitution, mice were injected with L. major amastigotes and progression was followed using clinical, parasitological and immunological criteria. As previously reported, BALB/c Xid mice showed a significant reduction in disease progression. In contrast, despite the dramatic reduction of B-1 cells, B-1-depleted BALB/c mice showed similar or even worse disease progression compared with control BALB/c mice. No differences were found between B-1-depleted or control C57Bl/6 mice. Our data suggest that the B-1 cells do not contribute to the susceptibility of BALB/c mice to L. major infection.

Actins↗
PubMed1999

Molecular epidemiology of poliovirus infection in Tunisia.

This report is an overview of poliomyelitis surveillance in Tunisia from 1991 to 1996. In all, 2088 stool specimens, collected from 152 acute flaccid paralysis (AFP) cases and from 1747 of their healthy contacts were investigated. Virus isolation was done systematically in RD and HEp-2C cell lines and isolated viruses were typed by sero-neutralisation as polioviruses or non-polio enteroviruses. Poliovirus isolates were analysed systematically for their wild or vaccine-related origin by two methods--one based on antigenic differences and one on genetic differences between strains. All type 2 polioviruses were vaccine-related and most wild viruses belonged to polio serotype 3. Wild polio type 3 viruses were detected in 1991 and 1992 in six cases of paralytic polio. A silent circulation of wild polio 1 and wild polio 3 was detected in 1994. No wild virus was detected in Tunisia from 1995 onwards. Wild polioviruses were sequenced and compared with Tunisian wild strains isolated during the 1980s, as well as other genotypes from the international database. These investigations revealed a single Tunisian polio 3 genotype that has been circulating from 1985 to 1994 and two different polio 1 genotypes. These results reflect effective control strategies within the country and contribute to the improvement of the polio eradication programme effectiveness at national and global levels.

Adolescent↗
PubMed1998

Antibodies to human myelin proteins and gangliosides in patients with acute neuroparalytic accidents induced by brain-derived rabies vaccine.

Antibody responses to myelin antigens were analysed in 15 patients who developed acute neuroparalytic accidents (ANPA) during post-exposure rabies vaccination using a rabies vaccine prepared on brain tissues and in 30 individuals who were uneventfully vaccinated. High titers (> or = 100) of IgG and IgM antibodies to GM1 or GD1a gangliosides were detected by enzyme linked immunosorbent-assay (ELISA) in plasmas from ANPA patients but not in controls. These data suggest that antibodies to GM1 and GD1a gangliosides may play a pathogenic role in the demyelinating and/or inflammatory processes characteristic of rabies vaccine-induced acute neurologic complications.

Adult↗
PubMed1998

[Agammaglobulinemia with the absence of circulating B-lymphocytes. 9 cases].

OBJECTIVES: Agammaglobulinemia with absence of circulating B lymphocytes is a rare genetically transmitted immunodeficiency that appears in early childhood and affect mainly boys. The clinical manifestations of the disease are rather heterogeneous. PATIENTS AND METHODS: Nine patients (7 boys and 2 girls) were diagnosed as suffering from agammaglobulinemia with absence of circulating B lymphocytes, over a period of 6 years. Quantitation of immunoglobulins and search for circulating B lymphocytes were respectively performed by the Mancini method and immunofluorescence using T specific (anti-CD3, anti-CD4 and anti-CD8) and B (anti-CD19) monoclonal antibody. RESULTS: The disease started to manifest clinically at the mean age of 8.7 months (4-16 months). The mean age at diagnosis is 4 years (1-11 years). The clinical manifestations were essentially recurrent infections of the lung and the gastrointestinal tract. However, bacterial meningitidis was observed in 3 patients. Severe complications such as an echovirus 27 meningoencephalitis and a chronic active hepatitis (1 patient) and a pericarditis (1 patient) were observed. All of our patients lacked circulating B lymphocytes and had low or null immunoglobulin levels. Five patients were treated by intravenous immunoglobulin (Ig) and 3 were treated by intramuscular immunoglobulin with a residual IgG level respectively of 5.5 g/l and 3.3 g/l. CONCLUSION: Recurrent infections are the principal manifestation of the agammaglobulinemia, early Ig treatment is the only therapy allowing improved.

Adolescent↗
PubMed1998

Effect of some variables on the in vivo determination of scorpion and viper venom toxicities.

An adequate assessment of scorpion and snake venom LD50 is an important step for accurate evaluation of antivenom sera potencies and the optimization of serotherapy. The LD50 variation of Tunisian scorpion (Androctonus australis garzonii: Aag and Buthus occitanus tunetanus: Bot) venoms with body weight, sex and strain (Swiss or C57BI/6) of mice used, the route of venom injection, the venom-milking procedures (manually or electrically) and the venom batches have been studied over a 7-year period (1990-1996). Aag venom is 3-4 times more toxic than Bot venom. However for both venoms, the LD50 determined in C57BI/6 mice, in small body weight animal or by intraperitoneal route were respectively significantly lower than those determined in Swiss mice, in high body weight or by subcutaneous route. Significant LD50 variations (25-50%) were also seen from one electrically prepared batch to another. A good correlation (r = 0.982) was observed between the concentrations of the crude venom toxic fraction determined by ELISA and LD50 values when assessed in vivo. The LD50 variation of Tunisian viper (Cerastes cerastes: Cc and Vipera lebetina: VI) venoms with the strain (Swiss or BALB/c), sex and body weight of mice used, the season and the year of venom milking were also investigated over a 3-year period (1990-1992). No significant LD50 variations were observed with the mouse strain, the sex or the season of venom milking. However, LD50 varies significantly with the year of the venom collection and the body weight of mice used. Furthermore, SDS-PAGE analysis shows annual variation for VI venom composition where no such variations were observed for Cc venom. These results stress the need either for the standardization of the venom LD50 evaluation or of the venom quality used for the development of an efficient antivenom.

Animals↗
PubMed1998

Development of an ELISA for the detection of scorpion venoms in sera of humans envenomed by Androctonus australis garzonii (Aag) and Buthus occitanus tunetanus (Bot): correlation with clinical severity of envenoming in Tunisia.

A sandwich ELISA was set up for measuring scorpion venom levels in sera of accidentally envenomed humans with the aim to establish a quantitative relationship between these levels, envenoming severity and clinical symptoms. This assay used equine polyclonal F(ab')2, specific to two North African scorpion (Androctonus australis garzonii: Aag and Buthus occitanus tunetanus: Bot) venoms. The test proved to be simple, reproducible, very sensitive (detection limit = 0.9 ng/ml) and linear between 0.5 and 15 ng/ml of venom concentrations. A large survey on scorpion sting envenomings was conducted from 1993 to 1996 in Tunisia to gather accurate epidemiological, clinical and biological data from victims as well as informations on the treatment that they had received. Victims were classified into three grades (GI, GII and GIII) of increasing severity according to clinical signs of envenoming. Blood samples were collected from victims and tested by ELISA for their content of Aag and Bot venoms. A strong correlation was found between clinical symptoms of envenoming and the level of scorpion venom antigens in serum (r = 0.980). Mean serum venom concentrations were: 2.65 +/- 0.81 ng/ml in GI envenoming, 9.79 +/- 4.08 ng/ml in GII and 21.7 +/- 6.51 ng/ml in GIII. The difference between each group was statistically significant (p < 0.01). This ELISA may prove to be helpful to establish a rationale approach of specific antivenom therapy.

Adolescent↗
PubMed1998

[Primary immunologic deficiency by deficiency of HLA class II antigens: nine new Tunisian cases].

BACKGROUND: Bare lymphocyte syndrome is a rare inherited primary immunodeficiency. The majority of the patients reported to date are from North Africa. We report nine new Tunisian cases. POPULATION AND METHODS: Over a period of 5 years, we have established the diagnosis of bare lymphocyte syndrome in nine patients who belong to seven different families. Class II HLA antigen expression was studied on resting peripheral mononuclear cells and PHA blasts. RESULTS: The clinical symptoms started at the mean age of 4.5 months (2-10 months) with chronic diarrhea. The evolution was characterized by appearance of other recurrent infections: pneumopathies (seven cases), thrush (seven cases), otitis (five cases) and septicemia (four cases). Allergic manifestations were observed in four cases. Six patients died at the mean age of 30 months from severe denutrition. Class II HLA antigens were not expressed on resting and activated lymphocytes. The absolute count of TCD4+ lymphocytes was decreased in seven patients. Lymphoproliferative response to specific antigens was absent. Four patients had panhypogammaglobulinemia. CONCLUSION: This study confirms the frequency of this disease among the North African population. The severity of the recurrent infection suggests the diagnosis of bare lymphocyte syndrome. This disease is fatal in the absence of bone marrow transplantation.

Child, Preschool↗
PubMed1998

Immunologic determinants of disease evolution in localized cutaneous leishmaniasis due to Leishmania major.

Localized cutaneous leishmaniasis caused by Leishmania major is polymorphic in its clinical presentation and evolution. Clinical and parasitologic features and disease evolution of 112 Tunisian patients was evaluated. The expression of interleukin (IL)-4, IL-6, IL-10, IL-12 (p40), interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha mRNA was analyzed by reverse transcription-polymerase chain reaction in 73 biopsies. Cytokine mRNA expression varied individually over a wide range; TNF-alpha, IL-6, and IFN-gamma were detectable in >90% of lesions, IL-12 and IL-10 in 40% and 70%, respectively, and IL-4 in only 9%. Statistical analysis demonstrated positive association between the level of IL-12 and IFN-gamma and the presence of parasites in the lesions. Unfavorable evolution of the lesions was positively associated with high IL-10, IL-12, and IFN-gamma mRNA expression. These results indicate that an unfavorable clinical outcome was not related to an inadequate Th1 cell response and suggest that the macrophage-activating effect of IFN-gamma may be inhibited by the concomitant expression of IL-10.

Animals↗
PubMed1998

[Activated protein C resistance in Behçet disease].

Behçet's disease is a systemic condition of unknown cause characterized in 20 to 40% of cases by venous and/or arterial thrombosis that is not fully explained by the hemostasis disorders reported in the literature. The present study investigated resistance to activated protein C in 65 Behçet's disease patients, 75 normal subjects, and 70 patients with a history of isolated thrombosis. The test used involved predilution in factor V-deficient plasma. Activated protein C resistance was found in six Behçet's disease patients (9.2%), eight normal subjects (10.6%), and 21 patients with isolated thrombosis (30%). Of the 26 Behçet's disease patients (40%) with a history of thrombosis, only one had activated protein C resistance. Activated protein C resistance does not explain the increased risk of thrombosis in Behçet's disease patients.

Activated Protein C Resistance↗
PubMed1997

Protein S deficiency and antibodies to protein S in patients with Behçet's disease.

Thrombosis occurs in 20 to 30% of patients with Behçet's disease (BD). Most of the reported hemostatic abnormalities are related to the inflammatory syndrome. We have assessed the activity of antithrombin III, protein C and protein S (PS), in 30 patients with BD and in 30 healthy controls. Thrombosis antecedents were found in 16 patients. Antithrombin III and protein C were within the normal range, however free PS and PSactivity were significantly decreased in patients as compared to control group. PS deficiency detected in eight patients, was associated to thrombosis in 6 of them. No correlation was found between free PS/total PS ratio and C4bBP levels. Antibodies to PS were screened by ELISA and were present in 6 patients, associated to PS deficiency in 4, and to thrombosis antecedents in 5 cases. PS deficiency was transient in two patients, associated to a persistent antiPS in one of them. These findings suggest that auto-immune acquired PS deficiency may be involved in the pathogenesis of thrombotic events in BD.

Adult↗
PubMed1997

Further characterization and thrombolytic activity in a rat model of a fibrinogenase from Vipera lebetina venom.

Vipera lebetina fibrinogenase (VlF) was shown to render fibrinogen incoagulable and to solubilize fibrin. The fibrinogenolytic activity of this enzyme was found to be 33 mg fibrinogen/min/mg protein. The study of the specificity of this enzyme revealed that it has no effect on purified factor X, prothrombin and protein C and on the specific chromogenic substrates of their active form. Plasminogen was not activated by VlF but slightly degraded. We have also compared the effect of VlF and plasmin on fibrinogen and shown that these two enzymes have a different sites of cleavage. This enzyme inhibited human platelet aggregation on PRP initiated by ADP and collagen but was without effect on the aggregation of washed rabbit platelets using thrombin as agonist. Administration of VlF in rat did not show any necrosis or hemorrhage in treated rats organ's. We therefore, examined the thrombolytic activity of VlF in a rat model of venous thrombosis. Thrombus was produced in the posterior vena cava by injection of human fibrinogen and thrombin. Injection of 5 mg/Kg body weight showed an evident flow restoration after one hour and measurement of the fibrinogen level a decrease of about 30% after 3 hrs. VlF's action is not dependent on plasminogen activators and may act synergistically with them, thereby providing an intriguing potential clinical application for dissolution of blood clots.

Animals↗
PubMed1997

Carbonic anhydrase II (CA II) deficiency in Maghrebian patients: evidence for founder effect and genomic recombination at the CA II locus.

A splice junction mutation at the exon 2-intron 2 boundary of the carbonic anhydrase II (CA II) gene was previously shown to be the unique mutation underlying the CA II deficiency syndrome in patients of Arab descent. Fourteen Tunisian (Maghrebian) families with a history of osteopetrosis, renal tubular acidosis, mental retardation, and CA II deficiency were studied to test the hypothesis that the mutation, found in all 24 patients, derived from a common ancestor originating in the Arabic Peninsula. A filiation study permitted us to trace these families back to a common Arabic tribe that settled in the Maghreb in the tenth century, indicating a common ethnic origin for these families. Segregation of the mutation with a TaqI biallelic restriction site polymorphism upstream of the CA II gene was studied by sequence-tagged site analysis in all the family members. These studies showed cosegregation of the Taq (-) allele with the mutation in 12 families out of 14. This observation supports a founder effect to explain the common CA II deficiency allele in this population. In the remaining two families, a genomic recombination or gene conversion occurred between the TaqI restriction marker and the mutation causing the disease. The relatively high recombination frequency suggests the presence of a hot spot for recombination or gene conversion at the CA II locus.

Acidosis, Renal Tubular↗
PubMed1997

Influence of host related factors on the antibody response to trivalent oral polio vaccine in Tunisian infants.

The low efficiency of trivalent oral polio vaccine (TOPV) in inducing protective antibody titres to polio3 is a problem of great importance in many regions of the world. A prospective study was conducted in 121 Tunisian infants aged 3 months during routine immunization with TOPV under carefully controlled conditions. Seroconversion rates to polio1, polio2 and polio3, one month after the third dose, were 94.7, 100 and 89.5%, respectively. The kinetics of the antibody response showed delayed and more difficult responses to polio3 compared to polio2 and polio1. The following host related factors, previously suggested to interfere with the immune response, were assessed: maternal antibodies; breast-feeding; concurrent enteric infections; and other illnesses. The main factor associated with the lack of seroconversion was concurrent infection with non-polio enteroviruses (NPE) which was found in 50% of non-responders to polio1 and/or to polio3 during the vaccination protocol whereas no NPE was isolated in vaccine responders. The other studied factors seemed not to interfere in the infants according to the locally adopted vaccination schedule and to the specific socio-economic conditions.

Antibodies, Viral↗