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M Kazanji

Publications and source records attributed to M Kazanji.

30 records · Page 2Linked to original sources

Antinuclear autoantibodies in human T-cell leukemia/lymphoma virus type I carriers in French Guiana.

To compare the rate of antinuclear antibodies (ANA) in HTLV-I carriers and negative individuals in French Guiana, 350 sera (175 HTLV-I carriers, either symptomatic or not, and 175 controls) were screened for ANA, using an immunofluorescence assay. All positive sera were tested for autoantibodies against extractable nuclear antigens, histones and double stranded DNA. ANA were detected in 9.71% of the HTLV-I carriers and 3.43% of the control group (p < 0.05). There was no difference in ANA distribution by age, sex, or ethnic group. Neither was there any difference between asymptomatic and symptomatic HTLV-I individuals. However, ANA of medical interest were significantly higher (p < 0.04) in HTLV-I seropositive Creoles than in seropositive Noir-Marrons.

Antibodies, Antinuclear↗

Evidence in Gabon for an intrafamilial clustering with mother-to-child and sexual transmission of a new molecular variant of human T-lymphotropic virus type-II subtype B.

Following the observation of an HTLV-II seropositive 60-year-old woman living in Gabon (Central Africa), a serologic and molecular study of her family members was conducted in an attempt to determine the duration of the HTLV-II infection and the modes of transmission of the virus. Among 41 family members, five were HTLV-I seropositive and 7 exhibited specific HTLV-II antibodies in their sera as demonstrated by high immunofluorescence titers on C19 cells and/or specific Western-blot pattern. The second husband of the index case and two of his sisters were infected by the virus, suggesting the presence of HTLV-II in this family over two generations. Sequence analysis of an amplified fragment of 172 nucleotides within the gp21 of the env region (6469-6640) of four HTLV-II infected individuals revealed a new HTLV-II molecular variant of the subtype b diverging from the prototypes NRA and G12 by seven (4.1%) and five (2.9%) bases substitutions, respectively. Molecular analysis of the total env gene (1462 bp) and fragments of the pol and pX regions confirmed that this new African variant was the most divergent HTLV-II subtype b yet described, exhibiting 2.3% of nucleotide substitutions in the env gene (33 bases) as compared to the two HTLV-II b prototypes. These data demonstrate, for the first time in Africa, intrafamilial both mother-to-child transmission and sexual transmission between spouses of an HTLV-II b molecular variant, and also suggest that this virus has been present in Gabon for a long period of time.

Adult↗

An HTLV-I/II vaccine: from animal models to clinical trials?

A human T-lymphotropic virus type I/II (HTLV-I/II) vaccine is necessary in view of two etiologically related, life-threatening diseases, namely, adult T-cell leukemia/lymphoma and tropical spastic paraparesis/HTLV-I-associated myelopathy. When the risk of developing autoimmune diseases such as uveitis, polymyositis, and arthritis is included, one can estimate the life-long risk of infected individuals to develop an HTLV associated pathology as approximately 10%. The populations at risk are, in a large majority, from developing countries but the epidemic of HTLV-II infection in intravenous drug users (IVDU) represents a possible reservoir for dissemination in the general population. The number of HTLV-I-infected individuals (15 to 25 million), together with the severity of associated disease, justifies the development of a vaccine. Different vaccine preparations have been developed, using mostly recombinant pox and adenoviruses, but DNA plasmid technology will soon become a feasible approach. Various animal models exist for experimental viral infections, involving rats, rabbits, or monkeys, but up to now, neither hematological nor neurological disorders have been induced by HTLV infection in such animal models. For long-term protection from HTLV-I-associated diseases, vaccination should induce both neutralizing antibodies and specific cell-mediated immunity. This will require the incorporation of both env and gag coding sequences in the vaccine preparations. Preventive clinical trials may involve different cohorts of seronegative young girls from endemic areas prior to sexual activity and IVDU in the industrialized world. In parallel, one should consider therapeutic vaccine trials in HTLV-I-positive mothers and IVDU to protect them against disease development. The observed rate of seroconversion in these different cohorts makes such trials feasible.

Animals↗

Human T cell lymphotropic virus: necessity for and feasibility of a vaccine.

Human T cell lymphotropic virus types I and II (HTLV-I/II) are endemic in certain areas of the world. They cause two life-threatening diseases, adult T cell leukaemia/lymphoma and tropical spastic paraparesis. A vaccine is needed because in developing countries there are no other feasible preventive interventions against these diseases and in Western countries intravenous drug users at high risk for HTLV-I and HTLV-II infections and the health workers in contact with such populations must be protected. We have developed a rat model in which we observed variations of susceptibility to viral infection between inbred strains, the most susceptible being the Fischer F344, and the possibility of viral latency in the nervous system. We have prepared a recombinant adenovirus vector that expresses the HTLV-I envelope glycoprotein env in HeLa cells. A target human population in French Guyana, in which the prevalence rate reaches 5.6% in one ethnic group (Bonis), has been identified for possible intervention.

Disease Models, Animal↗

Production and characterization of monoclonal antibodies directed against Eimeria falciformis and cross-reactive with sporozoites from two species of avian coccidia.

Monoclonal antibodies (mAbs) were obtained against the surface antigens of the Eimeria falciformis sporozoite by immunizing mice with whole homogenized sporozoite. The hybridomas were selected by their reactivities against oocyst extracts, then against glutaraldehyde-treated sporozoites. Three mAbs recognized both the surface of E. falciformis, E. tenella, and E. acervulina and their refractile bodies, whereas a fourth mAb recognized only one epitope on the refractile bodies. All mAbs bound to the same immunoaffinity-purified antigens in Western-blot analysis (P27 for E. falciformis and P25 for E. tenella and E. acervulina). Thus, the mAbs define at least two shared epitopes between sporozoite antigens from different eimerian species. Two of these mAbs are involved in the in vitro phagocytosis of E. falciformis sporozoites by macrophages and also in their lysis by neutrophils. Altogether, these properties showed that the four mAbs came from different activated B-cells. The P27 antigen recognized by our mAbs represents a major target of the in vitro destructive immune response.

Animals↗

The immunodominant Eimeria acervulina sporozoite antigen previously described as p160/p240 is a 19-kilodalton antigen present in several Eimeria species.

A lambda Zap II cDNA expression library, constructed from Eimeria acervulina (PAPa46 strain) sporulated oocyst stage, was screened with sera raised to E. acervulina or Eimeria tenella oocysts in order to isolate clones coding for antigens common to the two species. Most of the clones isolated were derived from the same gene. Antisera raised to a recombinant glutathione-S-transferase fusion protein 1P reacted with an antigen of 19 kDa in immunoblot of E. acervulina sporulated and unsporulated oocysts. Immunofluorescence of E. acervulina sporozoites indicated that the antigen is located in the cytoplasm. The anti-1P antisera reacted on immunoblots of E. tenella with a 19-kDa antigen and by immunofluorescence on E. tenella, Eimeria maxima and Eimeria falciformis sporozoites, indicating that the antigen is conserved in Eimeria species. DNA sequencing indicated that the sequence was almost identical to that of clone cSZ1 previously described by Jenkins et al. using E. acervulina strain #12. The 1P insert hybridized to a 1150-nt mRNA from E. acervulina PAPa46 strain and strain #12, a size consistent with the observed molecular weight of the protein.

Amino Acid Sequence↗

Immune responses and protective effect in mice vaccinated orally with surface sporozoite protein of Eimeria falciformis in ISCOMs.

Immunostimulating complexes (ISCOMs) were built after treatment of a purified surface protein from Eimeria falciformis sporozoites with a palmitic acid derivation, leading to a high ratio (33-64%) of P27 incorporation in these cage-like structures. P27 kept its antigenicity after incorporation in ISCOMs, which induced, after iterative intubations by the oral route to groups of mice, a systemic IgG response, a local IgA response, and a local enhanced cellular response as demonstrated by lymphoproliferation of mesenteric lymph node cells upon in vitro stimulation with antigen. This immunization (120 micrograms in six oral doses at 2-day intervals) afforded mice a partial protection (60%) against a subsequent 400 oocyst challenge. The reduction in daily oocyst excretion was corroborated by significantly different weight losses between immunized and control mice on days 9 and 10 postinfection and the subsequent death of these control mice. These observations provide the first application of ISCOMs to parasitic intestinal diseases.

Administration, Oral↗

Protective oral immunization of chickens against Eimeria tenella with sporozoite surface antigens.

Antigens were extracted from the surface of Eimeria tenella sporozoites with a solution containing Triton X 100 (1%), sodium dodecyl sulphate (0.5%) Na deoxycholate (1%) and EDTA (1 mM). After removal of the detergents, these surface antigen preparations conferred an immunity that protected chickens against a subsequent infection (10(4) sporulated oocysts). The best results were obtained after two 250 micrograms injections of Al(OH)3 adsorbed antigens (oocyst output per g caecal material on Day 7 post infection: 2.39 x 10(7) +/- 0.32 x 10(7) oocysts for controls and 7.37 +/- 10(6) +/- 3.19 x 10(6) oocysts for vaccinated birds) and after four gastric intubations of liposome entrapped antigens (oocysts output on Day 7 postinfection: 2.75 x 10(6) +/- 2.02 x 10(6) g-1 caecal material). These results represented respectively 70 and 88% protection indexes. Studies on the systemic and local antibody response after one or several infections of chickens with the parasite indicated at least 20 different molecules in the detergent antigens which are classified after immunoblotting according to their properties.

Administration, Oral↗

[Eimeria tenella and Eimeria acervulina: an antigenic stimulation in vitro of cells from immune chickens induced by adoptive transfer of protection against avian coccidiosis].

The transfer of 5 x 10(7) or 10(8) spleen cells from E tenella-infected chickens to virgin animals after 12-20-h in vitro stimulation with whole sporozoite homogenates confers significant protection to recipients. The oocyst contents of ceca on d 7 post-infection with 20,000 E tenella oocysts were (1.33 +/- 1.10) x 10(6) in chickens which received 5 x 10(7) immune cells after 20-h in vitro stimulation and (4.64 +/- 2.85) x 10(6) in chickens receiving 5 x 10(7) stimulated cells from normal chickens (85% protection). Adoptive transfer by spleen cells revealed an asymmetric cross-protection between E tenella and E acervulina. Spleen cells from E tenella immune chickens protected only against a subsequent infection with the same parasite, while spleen cells from E acervulina immune chickens protected against infection with E acervulina (78%) but also against infection with E tenella (68% protection). The common antigen permits better stimulation, but common surface sporozoite antigens purified from E tenella sporozoites via anti-E acervulina biliary antibodies are capable of stimulating both types of cells without, however, changing their properties.

Animals↗

In vitro interactions between murine neutrophils and Eimeria falciformis sporozoites.

The in vitro interactions between elicited mouse peritoneal neutrophils, antibodies and newly excysted sporozoites of Eimeria falciformis resulted in lysis of the parasite. This lysis required the presence of a heat-labile component of normal mouse serum, and was antibody- and cell-concentration-dependent. Under optimal conditions (serum dilution = 1/192, effector cell/sporozoite = 10/1) this lysis, which began after incubation at 37 degrees C for 4 h, was nearly complete after 18 h. It began by opsonization of the sporozoites by antibodies and complement. Inhibition studies performed with inhibitors of neutrophil function did not enable us to determine the mechanism of this extracellular lysis (oxidative respiratory burst or enzyme release), since only metal chelators, lysosomotropic reagents and compounds known to interfere with adenylate cyclase activity were truly inhibitory.

Aminophylline↗