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T H Duong

Publications and source records attributed to T H Duong.

At least 19 recordsLinked to original sources

The role of DNA-protein salt bridges in molecular recognition: a model study.

A theoretical study is presented of the influence of salt bridges between cationic side chains and DNA phosphates on DNA conformation and flexibility. The DNA sequence studied is that of the catabolite activator protein binding oligomer from the crystallized complex. The effect of salt bridges is modeled by neutralization of net phosphate charges for the groups involved in such interactions in the crystallized complex. Energy-optimized conformations are obtained by molecular mechanics using the JUMNA program. Base sequence dependence is studied by moving the phosphate neutralization pattern along the sequence and also by point mutations. Normal mode analysis is used to evaluate DNA flexibility. The results obtained show that the free oligomer is already precurved in the direction favored by the protein, and the effect of phosphate neutralization is principally to increase this curvature. This effect is, however, strongly sequence dependent. In addition, it is shown that oligomer flexibility cannot be explained by a simple superposition of the properties of successive dinucleotide steps, strong long-range coupling effects are observed. In all the cases examined, phosphate neutralization, however, leads to a reduction in oligomer flexibility.

Base Sequence↗

Sequence specificity of bacteriophage 434 repressor-operator complexation.

The binding affinity of the bacteriophage 434 repressor for its DNA operator depends strongly on the nature of two central base-pairs that are not in contact with the dimeric protein. In order to investigate the origin of this sequence specificity, we carried out molecular modelling of five model operators with central TA, AT, CG, GC and IC sequences. The five oligomers were studied both before and after complexation with the N-terminal binding domain of the 434 repressor. The relative importance of nucleic acid flexibility on operator-repressor binding was studied via a low frequency normal mode analysis using an internal coordinate method that we developed recently. The results suggest a higher twisting flexibility for TA and AT central steps than for CG, GC or IC steps, but the differences appear to be too small to account for the strength of repressor binding. An energetic analysis of the model operator-repressor complexes reveals rather that the preference for A.T and T.A base-pairs is electrostatic in origin and is linked to the presence of cationic Arg43 side-chains of repressor. This conclusion is supported by comparison with an R43A mutant and correlates with the sequence dependence of the electrostatic potential in the central minor groove of the operators.

Coliphages↗

Short- and long-term action of multiple doses of ivermectin on loiasis microfilaremia.

One hundred nine Gabonese patients infected with Loa loa microfilariae were treated with ivermectin (200 microg/kg of body weight) at the Parasitology, Mycology and Tropical Medicine Department (Faculte de Medecine et des Sciences de la Sante, Libreville, Gabon). Each was given one dose per month for six consecutive months. The peripheral blood microfilaria (mf) count before and after each dose showed an average decrease in the microfilaremia of 87.3% (short-term-single dose). An annual single-dose mass treatment with 200 microg/kg of ivermectin was sufficient to control the parasite in populations with low (< 400/ml) L. loa mf counts. One month after the sixth dose (short-term-multiple doses), the average microfilaremia rate had decreased by 99.2% compared with the initial infection (35 patients). Samples were taken from 28 patients one month after the first dose and one month after the sixth dose. The average mf count decreased by 96.4% after the first dose and by 99.6% after the sixth dose (average residual mf counts = 13.7 and 1.5 mf/ml, respectively). The mf count after the sixth dose was only 11.2% of the count after the first dose. The low mf count persisted for more than six months after the sixth treatment (long-term-multiple doses). Thus, mass treatment with multiple doses is more appropriate for areas where the blood mf count is very high. These results show that the number of the annual treatments used in mass chemotherapy with ivermectin can be adapted to each population to provide efficient protection.

Adolescent↗

Light microscopic changes in Plasmodium falciparum from Gabonese children treated with artemether.

The changes in Plasmodium falciparum in four Gabonese children suffering from severe malaria and treated with pure artemether were observed in thin blood smears fixed and stained with Giemsa and examined by light microscopy. Peripheral blood samples were taken every 8 hr up to 72 hr from three children and every 3 hr up to 9 hr from the other child. The morphologic changes involved all development stages (trophozoites, schizonts, and gametocytes); they were first seen 3 hr after the start of treatment and all parasites were abnormal after 24 hr. After two days of treatment, all infected erythrocytes disappeared except for a few with necrotic trophozoites. The morphologic changes were similar to the ultrastructural changes previously described in vivo and in vitro in experimental models. They confirm the rapid effect of artemisinin derivatives on parasite clearance and clinical recovery, particularly in cases of cerebral malaria.

Animals↗

[Aspects of malaria in the hospitalized child in Gabon].

To gain insight into the impact of malaria on children in terms of frequency and severity, a study was carried out in a department of the Owendo Children's Hospital in Libreville, Gabon, a fully endemic area. Diagnosis of Plasmodium falciparum malaria was confirmed by blood smears in 295 of the 1592 children admitted in 1992, i.e. 18.5% of admissions. Malaria was therefore the primary cause of hospitalization. Of 122 deaths observed during the study period 9 were due to malaria-associated complications for an overall mortality rate of 7.4% and malaria-related mortality rate of 3.1%. These rates are low in comparison with those reported by other departments in Central Africa. Convulsions were observed in 30.5% of children in the department and malaria was the underlying cause of convulsions in 62.9% of these cases. Severe anemia (< 5 g/dl) was noted in 23.7% of children overall and was associated with malaria in 54.7%. Severe malaria as defined by the criteria of the World Health Organization was observed in 33.2% of children. These findings illustrate the extent of the impact of endemic malaria on children in Gabon and emphasize the need to promote malaria control programs and improve treatment.

Age Distribution↗

[Cryopreservation of isolates of Toxoplasma gondii in cell culture].

For a better preservation and identification of Toxoplasma gondii isolates, we propose a new method of freezing of toxoplasma growth in THP-1 cell culture. A cystogenic strain isolated from foetal blood has been grown in these cells and frozen in liquid nitrogen. After thawing, toxoplasma recover the same growth rate and morphology in vitro and the same capacity to form brain cysts into mice compared to the initial strains. The freezing of the cell suspension provides a simple and appropriate method for preservation of Toxoplasma gondii within "bank" isolates.

Animals↗

[Variation of cholostase enzymes (5'-nucleotidase and alkaline phosphatase) during a specific treatment for malaria in the Gabonese child].

Biological variations of 5'nucleotidase (5'NU) and alkaline phosphatase (AP) in 102 Gabonese children with malaria features (MF) and malaria infection (MI) receiving treatment are reported. [formula: see text] During the therapeutic assay, 5'NU rate decreases faster than AP'S; Fourteen days after the beginning of treatment, difference between AP MF and AP M1 is still significant. Enzymes decrease is an indication of the malaria drugs tolerance (MSP (*)).

5'-Nucleotidase↗

Evaluation of Onchocerca volvulus-specific IgG4 subclass serology as an index of onchocerciasis transmission potential of three Gabonese villages.

The major objective of this study was to evaluate the usefulness of IgG4 ELISA and Western blot analysis, using a crude extract of Onchocerca volvulus adult worms as antigens, for diagnosing onchocerciasis in a Gabonese paediatric population with mixed filarial infections. The subjects had loaisis, streptocercosis or mansonellosis in addition to onchocerciasis. Control sera from loaisis or mansonellosis subjects residing outside the endemic zone were used to provide the cut-off point for positive results. The IgG4 ELISA had a specificity of 96% but a lower sensitivity of 78.7%. It detected 25 onchocerciasis cases out of 65 individuals who were negative on parasitological examination. Furthermore, the ELISA provided a more accurate picture of onchocerciasis transmission in a village with very low skin microfilarial load. A 27.5-kD antigen was identified on Western blots as a marker of onchocerciasis. The paediatric population provided a reliable window for assessing the parasitologic and serologic parameters in the three villages with disparate levels of onchocerciasis transmission.

Adolescent↗

[Bilharziasis caused by Schistosoma intercalatum, a recent and forgotten form of schistosomiasis].

Schistosoma intercalatum schistosomiasis is confined to the western regions of equatorial Africa. It is often asymptomatic but it produces microscopic lesions in the intestine (mainly the rectum), the liver and the genital organs of both men and women, the latter lesions being more insidious and insufficiently explored. Its treatment, like that of other schistosomiases, consists of one course of praziquantel. Naturally, S. intercalatum may be hybridized with S. haematobium in Gabon and Cameroun which are the two countries where the two parasites coexist.

Animals↗

Elevated antifilarial IgG4 antibody levels in microfilaremic and microfilaridermic Gabonese adults and children.

Immunologic analyses of sera from 47 selected individuals living in a mixed filariasis transmission zone in Gabon were carried out. Onchocerca volvulus, Loa loa, Mansonella streptocerca, and M. perstans are transmitted in this region. Based on parasitologic findings and age, the 47 individuals were stratified into four groups: microfilaria negative (Mf-) children (3-15 years old), Mf- adults (> 15 years old), microfilaria positive (Mf+) children and Mf+ adults. For descriptive purposes, the term microfilaria positive refers to individuals with skin and blood microfilariae. Antifilarial antibody titers were determined using an enzyme-linked immunosorbent assay with Dipetalonema viteae antigens. In general, children had higher titers of IgG antibodies than adults. For the IgG1, IgG2, and IgG3 subclass responses, both age and microfilarial status appeared to be important variables since Mf- children consistently had the highest titers whereas Mf- adults had the lowest titers. For the IgG4 antifilarial response, only the microfilarial status was an important variable. All Mf+ individuals had significantly higher levels of IgG4 antibody than Mf- individuals. Pooled sera of Mf- and Mf+ individuals reacted with similar O. volvulus antigens on Western blots. Control sera of individuals who did not reside in the study area, but who had single infections with L. loa or M. perstans, did not react with any O. volvulus antigens.

Adolescent↗

[Evaluation of 3 tests applied in the immunological diagnosis of hepatic amebiasis in Gabon].

The diagnosis of hepatic amoebiasis is not always easy. In case of suspicion of hepatic amoebiasis in an endemic area, the patient is immediately treated with a 5-nitroimidazole. Immunological diagnosis is indispensable. After a comparative study of BLA, IHA and IFA reactions, the BLA test has shown to be well adapted to the context of a country with insufficient sanitary infrastructure. The BLA test is easily performed and enables rapid detection of antibodies. The result obtained in about 5 minutes allows to adjust the therapeutic conduct.

Adolescent↗

[Seroepidemiological study of toxoplasmosis in Libreville, Gabon].

A sero-epidemiological survey of toxoplasmosis has been carried out in 1178 subjects residing in urban and suburban areas of Libreville, Gabon. Two techniques were used: Pastorex toxo of the Institut Pasteur and ISAGA of bioMérieux. The acquisition of antibodies occurs at an early age, from the age of six months on. After the age of 15 years, the age of procreation, the prevalence is 68%. Between the ages of 15 and 19 years, 19% have IgM. The risk for toxoplasmosis acquired during pregnancy is not to be neglected. It decreases between the ages of 20 and 30 years. The most probable source of contamination is the reservoir from the soil. No difference between the sexes was observed.

Adult↗

[Toxoplasmosis in Gabon. Results of a seroepidemiological investigation].

A toxoplasmosis sero-epidemiological inquiry was effected with 2,324 sera collected from Libreville, Lébamba, Makokou, Lastourville and Woleu-Ntem. All the sera were first screened through Pastorex toxo (Diagnostics Pasteur). Those with more 8 IU/ml and 267 sera with less 8 IU/ml were then assayed by ISAGA (bioMerieux) for IgM. The results of ISAGA must be interpreted with carefulness for natural agglutinins are frequent in this population. The acquisition of immunity is precoce and more of 60% have a serology positive from ten years old. There was no difference between sex.

Adolescent↗

[Results of a systematic search for Plasmodium in internal medicine in Gabon].

Among 158 adults hospitalized at the University Hospital of Libreville who did not receive any treatment against malaria before blood screening, 20 were carriers of malaria parasites. Plasmodium falciparum was seen in 19 cases with a parasitic density lower than 1,000 trophozoits/mm3 of blood in 18 cases. The most important prevalence was observed into the group of older people. In most cases symptoms related to malaria did not occur during the hospitalization. We conclude that, in such patients, a parasitic density lower than 1,000 trophozoits/mm3 is not sufficient to assess the diagnosis of malaria and does not deserve systematic treatment.

Adolescent↗

[Role of cryptosporidiosis in infants in Gabon. Results of two prospective studies].

Two epidemiological surveys of cryptosporidiosis in urban and suburban areas of Libreville, Gabon, Equatorial Africa, were conducted in children. On 450 fecal samples on the first study, Cryptosporidium sp. has been seen about 3.11%. For the second survey, on 296 children, aged between 0 and 2 years, with acute diarrhoea, the rate of infestation was 24%. The maxima was observed for infants aged between 6-18 months, in case of malnutrition and during wet seasons.

Acute Disease↗

Successful treatment of acute fascioliasis with bithionol.

Fascioliasis is the parasitic infestation of the liver and biliary tract related to Fasciola hepatica. Bithionol is proposed as the treatment of choice for human fascioliasis without major side effects. However, the efficacy of bithionol has been evaluated in chronic but not in acute fascioliasis. In this study we report on the success of treatment with bithionol in 10 patients with fascioliasis, 8 having acute fascioliasis. The criteria for the diagnosis of fascioliasis were hypereosinophilia, positive immunoelectrophoresis and indirect hemagglutination. Bithionol was given orally to hospitalized patients at the daily dose of 25 mg/kg body wt for 10 days. Three patients with acute fascioliasis received a second course of bithionol 2 or 3 mo after the first because of the recurrence of diarrhea and fatigue in one patient and persistent hypereosinophilia in two patients. All patients were cured. The follow-up period after the first course of treatment was between 16 and 47 mo. No major side effects were observed. We conclude that bithionol is the drug of choice for both acute and chronic fascioliasis. Moreover, its oral administration may allow treatment of fascioliasis in outpatients who do not have serious symptoms.

Acute Disease↗