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Biomedical subjects

H Tolou

Publications and source records attributed to H Tolou.

13 recordsLinked to original sources

Characterisation of the binding sites of monoclonal antibodies reacting with the Plasmodium falciparum rhoptry protein RhopH3.

Twenty one mouse monoclonal antibodies reacting or cross-reacting with the Plasmodium falciparum RhopH3 protein reacted with Ag44, a recombinant antigen expressing the 134 C-terminal RhopH3 residues. Using overlapping peptides scanning this region, two major binding sites were identified. The first one, recognised by eight anti-RhopH3 and seven cross-reacting mAbs, was mapped to the sequence Thr Asp Asn Thr Tyr or Thr Asp Asn Thr Tyr Lys (aa 823-828), depending on the support used for synthesis. Binding specificity and affinity were investigated for a subset of four mAbs reacting with this epitope, including one growth inhibitory mAb. Systematic replacements showed that the various mAbs had similar requirements. The inhibitory mAb presented a higher affinity for this sequence and bound to the adjacent sequence, Tyr Lys Glu Met Glu Leu (aa 827-832). A 2nd binding site, located around residue 850, was recognised by two anti-RhopH3 mAbs, which reacted exclusively with the 110 kDa RhopH3 polypeptide, unlike the other mAbs, which reacted with the 110 and 105 kDa RhopH3 antigens. This suggested that the 105 kDa RhopH3 polypeptide derives from the 110 kDa by C-terminal processing. Experimental evidence substantiating this conclusion was provided by the observation that antisera raised to peptides located upstream of the putative cleavage site reacted with both the 110 kDa and 105 kDa polypeptides, whereas antisera raised to the 45 C-terminal amino acids of RhopH3 reacted exclusively with the larger, 110 kDa product. The biological significance of this processing is discussed.

Amino Acid Sequence

Homogeneity of yellow fever virus strains isolated during an epidemic and a post-epidemic period in West Africa.

Three strains of yellow fever virus (YFV) were isolated in 1982 in The Ivory Coast, one from a human case and two from Aedes luteocephalus, during and subsequent to an epidemic. The complete genomic sequence of the human strain was determined and compared to that of the 1927 Asibi strain of YFV. The divergence observed was on average of 8.3%, ranging from 5.5 to 11.7% in the coding region. The transitions to transversions ratio was 5.9. Most mutations (84.3%) occurred on the third position of the codons, with synonymous mutations representing 92.5%. However, when partial sequences representing 60% of each genome were compared, homology between the three Ivory Coast strains was greater than 99%. These results demonstrate the homogeneity of the virus strains circulating in different hosts and vectors in a limited geographical region and validate the concept of topotype in viral quasi-species.

Aedes

[Current status of dengue virus infections. Epidemiologic and pathogenetic aspects].

The epidemiology of dengue fever is changing dramatically. The worldwide incidence is rising and clinical symptoms are worsening. Reports describing forms associated with hemorrhage or shock syndrome involving both children and adults are increasingly frequent in regions beyond Southeast Asia where the first cases were observed. Many mechanisms could be implicated in these changes including modifications of the virus, host, vector, or socioeconomic factors. Since no current model allows laboratory analysis of these mechanisms, observation of epidemics is still a major source of data. The findings of well conducted epidemiological studies allow not only assessment of morbidity and mortality in endemic areas and early detection of epidemic outbreaks but also evaluation of socioeconomic impact and effectiveness of control measures. Surveillance techniques must be chosen in function of prevailing local conditions. To ensure reliable results studies should be carried out in collaboration with an international network and a simple and accurate method of disease identification should be used.

Adult

[Current status of dengue].

Dengue has become a major public health problem in intertropical areas where an estimated 60 million new cases and 30,000 deaths occur annually. The causative agent is transmitted by the bite of Aedes mosquitoes which are the main and perhaps only reservoir of the disease. In addition to increasing incidence clinical manifestations of dengue have changed over the last 40 years. An increasing number of reported cases involve hemorrhage, shock, and other severe complications especially in Southeast Asia, northern regions of South America, and the Caribbean. Some of the same factors responsible for these changes are probably implicated in the development of other emerging viral diseases.

Aedes

Partial inhibition of yellow fever virus replication in vitro with different phosphorothioate oligodeoxyribonucleotides.

Phosphorothioate oligodeoxyribonucleotides targeted to different regions of the viral genome were synthesized and used in two kinds of experiments testing their activity against yellow fever virus (YFV) replication in cultured cells. We found that oligonucleotides complementary to the 3'-end or to the coding region of the viral RNA were regularly active in plaque reduction assay, although with inconstant efficiency. Oligonucleotides targeted to the 5'-end or to the initiation codon region exhibited lesser activity. Homologous oligonucleotides targeted to dengue virus RNA had no detectable inhibitory activity against dengue virus replication. However, in YFV production reduction assay, a non-specific inhibitory activity of a random oligonucleotide was observed. Taken as a whole, our results indicate that flaviviruses present detectable but heterogeneous sensitivity to phosphorothioate inhibition. Possible explanations are discussed.

Animals

Partial genomic sequence determination of yellow fever virus strain associated with a recent epidemic in Gabon.

A limited epidemic, with important mortality among the initial human cases, occured in a forest region in the north of Gabon by the end of 1994. It was identified as yellow fever according to first serological and reverse transcription/polymerase chain reaction (RT-PCR) results, but no virus was isolated. We received 37 sera from people who lived in the same region and presented symptoms of the disease during the period of concern. In ten of them, we were able to detect and identify yellow fever virus (YFV) RNA by RT-PCR and endonuclease digestion of the RT-PCR products. Nucleotide (nt) sequence of two regions (242 and 161 nt long) of YFV RNA was determined for three sera. As it differed from that of the Asibi strain of YFV, the presence of a new topotype (strain) of YFV is presumed.

Base Sequence

Serum iron, glutamic oxalacetic transaminase and creatine phosphokinase in acute myocardial infarction. A comparative study.

The serum iron was subnormal on the first three days, following acute myocardial infarction in thirty patients. This is significantly less than the incidence of abnormalities demonstrated by assays of creatine phosphokinase (CPK) and glutamic oxalacetic transaminase (SGOT) in serum. Occasional patients had abnormal serum iron concentrations in association with normal CPK activities. For this reason serum iron determination may usefully supplement CPK activity measurements and possibly those of SGOT activity as an aid to the detection of acute myocardial infarction.

Adult