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Biomedical subjects

A Georges

Publications and source records attributed to A Georges.

At least 19 recordsLinked to original sources
PubMed2001

Assessment of brain natriuretic peptide in patients with suspected heart failure: comparison with radionuclide ventriculography data.

BACKGROUND: The aim of the study was to prospectively evaluate patients with suspected or known heart disease using plasma brain natriuretic peptide (BNP) measurement and radionuclide ventriculography to examine whether left ventricular dysfunction is associated with an abnormal rise of BNP concentration. METHODS: Patients (n=153) and controls (n=14) underwent radionuclide ventriculography to determine Left ventricular Ejection Fraction (LVEF) and measurement of plasma BNP concentration using a commercial kit. RESULTS: Plasma BNP concentration in controls was significantly lower than that in patients whatever the stage of the disease, significantly lower than that of patients with normal LVEF (LVEF>55%); than that of patients with altered LVEF (LVEF< or =40%); and than that of patients with moderately reduced LVEF (40%<LVEF< or =5%). Comparisons between groups of patients showed that the more severe the disease, the higher the BNP level. From the ROC curve, a plasma BNP concentration of 52 pg/ml was attached to a 85% sensitivity and 82% specificity in identifying patients with LVEF< or =40%. CONCLUSIONS: Plasma BNP concentration provides a reliable and sensitive marker of LV systolic dysfunction evaluated by a nuclear medicine technique, and could be a potential screening test to identify patients for additional investigations.

Cardiac Output, Low↗
PubMed2000

Coherence scale of the kondo lattice

It is shown that the large- N approach yields two energy scales for the Kondo lattice model. The single-impurity Kondo temperature, T(K), signals the onset of local singlet formation, while Fermi-liquid coherence sets in only below a lower scale, T small star, filled. At low conduction electron density n(c) ("exhaustion" limit), the ratio T small star, filled/T(K) is much smaller than unity, and is shown to depend only on n(c) and not on the Kondo coupling. The physical meaning of these two scales is demonstrated by computing several quantities as a function of n(c) and temperature.

Journal Article↗
PubMed2000

Mean field theory of a quantum heisenberg spin glass

A full mean-field solution of a quantum Heisenberg spin-glass model is presented in a large- N limit. A spin-glass transition is found for all values of the spin S. The quantum critical regime associated with the quantum transition at S = 0 and the various regimes in the spin-glass phase at high spin are analyzed. The specific heat is shown to vanish linearly with temperature. In the spin-glass phase, intriguing connections between the equilibrium properties of the quantum problem and the out-of-equilibrium dynamics of classical models are pointed out.

Journal Article↗
PubMed2000

Protection of cynomolgus macaque against cervicovaginal transmission of SIVmac251 by the spermicide benzalkonium chloride.

We evaluated the potential effectiveness of a spermicide cationic surfactant, benzalkonium chloride (BZK), to prevent the transmission of simian immunodeficiency virus (SIV) after intravaginal inoculation in 12 cynomolgus macaques. The inoculation procedure involved deposition of 6.7 ivag-AID50 of cell-free SIVmac251 into the receiving vagina, four times over a 2-week period, at the end of the luteal phase of the menstrual cycle. Six randomly selected females received vaginally foam containing BZK (7.37%, wt/wt) before each inoculation (BZK group), whereas the remaining were not pretreated (control group). In controls, 5 animals presented persistent SIV infection and 1 had a transient viremia. The number of uninfected animals was higher in the BZK group (6 of 6) than in controls (0 of 6). These findings demonstrate that BZK placed in the vaginal receptacle prior to SIV inoculation provides a significant protection in vivo. The wide spectrum of antimicrobial activities of BZK (including HIV) in addition to its efficiency to block the transmucosal passage of SIV in the macaque model qualifies this drug as an attractive topical microbicide to prevent sexually transmitted infections in humans.

Animals↗
PubMed1998

The rate of mitochondrial 12S rRNA gene evolution is similar in freshwater turtles and marsupials.

Assertions that the "conventional" rate of mitochondrial DNA (mtDNA) evolution is reduced in poikilotherms in general and turtles in particular were tested for side-necked turtles (Pleurodira: Chelidae). Homologous data sets of mitochondrial 12S rRNA gene sequences were used to compare the average divergence between the Australian and South American species for two Gondwanan groups: the chelid turtles and the marsupials. The mean nucleotide divergences between continental groups for both the turtles and the marsupials are remarkably similar. These data suggest that the rate of evolution of mitochondrial 12S rRNA gene is not substantially slower in turtles than in the homeothermic marsupials.

Animals↗
PubMed1998

Natural infection of a household pet red-capped mangabey (Cercocebus torquatus torquatus) with a new simian immunodeficiency virus.

A seroprevalence survey was conducted for simian immunodeficiency virus (SIV) antibody in household pet monkeys in Gabon. Twenty-nine monkeys representing seven species were analyzed. By using human immunodeficiency virus type 2 (HIV-2)/SIVsm, SIVmnd, and SIVagm antigens, one red-capped mangabey (RCM) (Cercocebus torquatus torquatus) was identified as harboring SIV-cross-reactive antibodies. A virus isolate, termed SIVrcm, was subsequently established from this seropositive RCM by cocultivation of its peripheral blood mononuclear cells (PBMC) with PBMC from seronegative humans or RCMs. SIVrcm was also isolated by cocultivation of CD8-depleted RCM PBMC with Molt 4 clone 8 cells but not with CEMx174 cells. The lack of growth in CEMx174 cells distinguished this new SIV from all previously reported sooty mangabey-derived viruses (SIVsm), which grow well in this cell line. SIVrcm was also successfully transmitted (cell free) to human and rhesus PBMC as well as to Molt 4 clone 8 cells. To determine the evolutionary origins of this newly identified virus, subgenomic pol (475 bp) and gag (954 bp) gene fragments were amplified from infected cell culture DNA and sequenced. The position of SIVrcm relative to those of members of the other primate lentivirus lineages was then examined in evolutionary trees constructed from deduced protein sequences. This analysis revealed significantly discordant phylogenetic positions of SIVrcm in the two genomic regions. In trees derived from partial gag sequences, SIVrcm clustered independently from all other HIV and SIV strains, consistent with a new primate lentivirus lineage. However, in trees derived from pol sequences, SIVrcm grouped with the HIV-1/SIVcpz lineage. These findings suggest that the SIVrcm genome is mosaic and possibly is the result of a recombination event involving divergent lentiviruses in the distant past. Further analysis of this and other SIVrcm isolates may shed new light on the origin of HIV-1.

Adaptation, Physiological↗
PubMed1998

Simian T-cell lymphotropic virus type 1 from Mandrillus sphinx as a simian counterpart of human T-cell lymphotropic virus type 1 subtype D.

A recent serological and molecular survey of a semifree-ranging colony of mandrills (Mandrillus sphinx) living in Gabon, central Africa, indicated that 6 of 102 animals, all males, were infected with simian T-cell lymphotropic virus type 1 (STLV-1). These animals naturally live in the same forest area as do human inhabitants (mostly Pygmies) who are infected by the recently described human T-cell lymphotropic virus type 1 (HTLV-1) subtype D. We therefore investigated whether these mandrills were infected with an STLV-1 related to HTLV-1 subtype D. Nucleotide and/or amino acid sequence analyses of complete or partial long terminal repeat (LTR), env, and rex regions showed that HTLV-1 subtype D-specific mutations were found in three of four STLV-1-infected mandrills, while the remaining monkey was infected by a different STLV-1 subtype. Phylogenetic studies conducted on the LTR as well as on the env gp21 region showed that these three new STLV-1 strains from mandrills fall in the same monophyletic clade, supported by high bootstrap values, as do the sequences of HTLV-1 subtype D. These data show, for the first time, the presence of the same subtype of primate T-cell lymphotropic virus type 1 in humans and wild-caught monkeys originating from the same geographical area. This strongly supports the hypothesis that mandrills are the natural reservoir of HTLV-1 subtype D, although the possibility that another monkey species living in the same area could be the original reservoir of both human and mandrill viruses cannot be excluded. Due to the quasi-identity of both human and monkey viruses, interspecies transmission episodes leading to such a clade may have occurred recently.

Amino Acid Sequence↗
PubMed1998

The environmental contaminant DDE fails to influence the outcome of sexual differentiation in the marine turtle Chelonia mydas.

In many turtles, the temperature experienced during the middle of egg incubation determines the sex of the offspring. The implication of steroid sex hormones as the proximate trigger for sex determination opens the possibility that endocrine-disrupting contaminants may also influence the outcome of sexual differentiation. In this study we investigate the potential effects of DDE (a common DDT metabolite) on sexual differentiation of Chelonia mydas (green sea turtle). Four clutches of eggs collected from Heron Island, Queensland, Australia, were treated with DDE at the beginning of the thermosensitive period for sexual determination. An incubation temperature of 28 degrees C or less produces male hatchlings in this species, whereas 30 degrees C or more produces female hatchlings. Dosed eggs were consequently incubated at two temperatures (27.6 degrees C and 30.4 degrees C) on the upper and lower boundaries of the sex determination threshold for this species. DDE, ranging from 3.3 to 66.5 microg, was dissolved in 5, 10, and 25 microl ethanol and applied to eggshells above the embryo. Less than 2.5 ng/g DDE was present in eggs prior to dosing. Approximately 34% of the applied DDE was absorbed in the eggs, but only approximately 8% of applied DDE was found in embryos. Thus, treated eggs, corrected for background DDE, had up to 543 ng/g DDE. The sex ratio at these doses did not differ from what would be expected on consideration of temperature alone. Incubation time, hatching success, incidence of body deformities, hatching size, and weight were also within the limits of healthy developed hatchlings. This indicates that the eggs of C. mydas in the wild with concentrations of DDE less than 543 ng/g should produce hatchlings with relatively high hatching success, survival rate, and normally differentiated gonads.

Animals↗
PubMed1998

[Human African trypanosomiasis, contributions of experimental models].

Melarsoprol has remained the chosen drug for the late-stage treatment of human African trypanosomiasis (HAT) due both to Trypanosoma brucei (T.b.) gambiense and T.b. rhodesiense; however, arsenical encephalopathies, which are often fatal, occur in 5-10% of the treated cases. To date, two major problems have not been solved. The first one is the precise diagnosis of early involvement of the central nervous system (CNS) which determines the therapeutics to be administered. The second one is linked to the lack of data on in vivo efficacy of products which are effective in vitro against trypanosomes. Answers have to be provided by experimental animal models of HAT. Such models would allow for better studies of the pathology and pathogenesis of the disease, as well as therapeutic trials of potentially effective new drugs or combinations. We have developed acute and chronic murine and sheep experimental animal models of HAT infected by T. b. brucei. Meningoencephalitis and neurological signs are relatively difficult to obtain in murine models and require artificial means, such as suramin treatment on day 21 after-infection. The chronic murine model has demonstrated CNS involvement with meningitis, followed by meningoencephalitis with progressive astrocytosis. The sheep model develops a disease with CNS complications and cerebrospinal fluid can be collected. In the sheep model, we have described anti-galactocerebrosides antibodies, which represent major components of myelin, which may indicate an autoimmune process in the CNS. We then described these antibodies in the cerebrospinal fluids and sera from patients at a late-stage of the disease. From a therapeutic point of view, we have cured mice or sheep with low doses of melarsoprol, or with the nitroimidazole derivatives Ro 15-0216 and megazol, alone or combined with suramin. Further studies of these nitroimidazole compounds, which could be proposed for human use, have to be carried out on a-primate model infected by T.b. gambiense. To our knowledge, this primate model is not available. This is why we have recently developed a T. b. gambiense primate model of HAT on Cercopithecus aethiops.

Animals↗
PubMed1997

Characterization and titration of an HIV type 1 subtype E chimpanzee challenge stock.

A subtype E human immunodeficiency virus type 1 (HIV-1) isolate from the Central African Republic (E/90CR402) was adapted to growth on chimpanzee peripheral blood mononuclear cells (PBMCs) by cocultivation of irradiated, infected human PBMCs with chimpanzee PBMCs. The resulting virus was passaged in chimpanzee PBMCs to generate a stock of chimpanzee-adapted virus. Although its V3 region sequence was identical to that of the parental isolate, the chimpanzee-adapted virus had a syncytium-inducing phenotype as opposed to the non-syncytium-inducing phenotype of the parental virus. After demonstrating in one animal each that the passaged virus could infect chimpanzees following intravenous (i.v.) or cervical inoculation, the i.v. infectious titer of the stock was determined. Exposure of three chimpanzees to different doses of the virus indicated that the titer was between 2 and 5 TCID50. Thus, the HIV-1 E/90CR402 chimpanzee challenge stock established persistent infections in chimpanzees by both the i.v. and genital routes and should be valuable for future HIV-1 vaccine studies to evaluate cross-protection between HIV-1 subtypes.

Animals↗
PubMed1997

Plasmodium falciparum: sickle-cell trait is associated with higher prevalence of multiple infections in Gabonese children with asymptomatic infections.

Through PCR amplifications of the gene encoding the merozoite surface antigen 2, utilizing allele-specific 3D7 and FC27 probes, we have examined the prevalence of Plasmodium falciparum in children aged from 7 to 14 years living in a village located in the equatorial forest region of Central Africa (Gabon). Using this technique, 61% (100/163) of the blood samples were shown to be infected with P. falciparum with 24 alleles distinguished by size polymorphism and sequence type. The two main families (3D7 and FC27) and hybrid alleles were detected regardless of sex and hemoglobin phenotype. No age-related changes in prevalence of P. falciparum strains were observed; however, the prevalence of infection (42%) was significantly lower in individuals with the sickle-cell trait compared with their normal-hemoglobin counterparts (68%). Mixtures of genetically distinct parasite clones were present in 82% of children carrying the sickle-cell trait but in only 58% of normal-hemoglobin carriers. The significance of these observations regarding the design and interpretation of epidemiological investigations is discussed in the context of malaria transmission in the region studied.

Adolescent↗
PubMed1997

Phylogenetic relationships of chelid turtles (Pleurodira: Chelidae) based on mitochondrial 12S rRNA gene sequence variation.

Conflicting phylogenies have been proposed for the Chelidae (Testudines: Pleurodira), a family of side-necked turtles found only in Australasia and South America. Sequence data from the mitochondrial 12S rRNA gene were used to test these phylogenies. In total, 411 nucleotides were sequenced for each of 16 chelid species, including all 11 recognized chelid genera and, as outgroups, 5 genera of Pelomedusidae (Testudines: Pleurodira). Analyses using parsimony and neighbor joining algorithms strongly support the division of Australian Chelidae into the three monophyletic groups initially suggested by Burbidge et al. (1974; Copeia 2: 392-409): Chelodina (bootstrap value 99%), the Emydura group (87%), and Pseudemydura. The analyses suggest that the Australian chelids are a monophyletic lineage (64%), with the Australian long-necked turtles, Chelodina, more closely related to the Australian short-necked chelids than to the long-necked South American species. These relationships are in contrast to those of Gaffney (1977; Am. Mus. Novitates 2620: 1-28). The species of Australian long-necked chelids consistently form a monophyletic clade, with Chelodina longicollis and Chelodina oblonga as sister taxa. The data failed to resolve relationships among the Australian short-necked taxa: Emydura, the Elseya latisternum group, the Elseya dentata group, Rheodytes, and Elusor. Unlike Gaffney (1977), we find some weak support (58%) for Pseudemydura as the closest relative of the other Australian short-necked taxa. With the exception of Hydromedusa, the South American taxa are monophyletic and the subgenera of Phrynops are paraphyletic.

Animals↗
PubMed1996

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↗
PubMed1996

Cervicovaginal synthesis of IgG antibodies to the immunodominant 175-199 domain of the surface glycoprotein gp46 of human T-cell leukemia virus type I.

Paired sera, saliva and cervicovaginal secretions from 17 HTLV-I-infected women (19-75 yr) were tested for total IgA and IgG, for IgA and IgG to the immunodominant region gp46/175-Pro-199, for serum IgG to the neutralizing domains gp46/ 190-Pro-199 and gp46/190-Ser-199, or for tax-rex proviral HTLV-DNA. Serum antibodies to gp46/ 175-Pro-199 were detected more frequently in the IgG (13/17) than in the IgA (5/17) isotypes. The majority (8/12) of anti-gp46/175-Pro-199-positive sera reacted also to gp46/190-Pro-199 or to gp46/ 190-Ser-199, demonstrating their neutralizing properties. In saliva, antibodies to gp46/175-Pro-199 were not generally detected. In cervicovaginal secretions, IgG to gp46/175-Pro-199, but not IgA, were detected in 6/15 (40%) patients. The mean specific activity of IgG to gp46/175-Pro-199 showed a trend to be higher in cervicovaginal secretions (218 +/- 109) than in sera (14 +/- 4). Furthermore, in all patients with cervicovaginal IgG to gp46/175-Pro-199, the cervicogaginal/serum ratio (19 +/- 6) of anti-gp46 IgG specific activities were markedly above 1. HTLV-DNA was detected in 4/17 salivas, and in 3/15 cervicovaginal secretions, all from patients demonstrating cervicovaginal synthesis of IgG to gp46/175-Pro-199. In conclusion, IgG to gp46/175-Pro-199 in cervicovaginal secretions, when present, appear to be produced primarily locally because of local HTLV-I excretion. Since anti-gp46/175-Pro-199 antibodies usually support reactivities to neutralizing domains, their presence could be relevant for limiting HTLV-I transmission via cervicovaginal secretions.

Adult↗
PubMed1996

Epidemiological and molecular characteristics of HIV infection in Gabon, 1986-1994.

OBJECTIVE: To describe trends in the prevalence of HIV-1 infection in different populations in Gabon, and the molecular characteristics of circulating HIV strains. METHODS: Data were collected on HIV prevalence through sentinel surveillance surveys in different populations in Libreville (the capital) and in Franceville. In Libreville, a total of 7082 individuals (hospitalized patients, tuberculosis patients, pregnant women, asymptomatic adults, prisoners) were recruited between 1986 and 1994. In Franceville, we tested 771 pregnant women and 886 healthy asymptomatic adults (1986-1988). Sera were screened for HIV antibodies by enzyme-linked immunosorbent assay (ELISA) and confirmed by Western blot or line immunoassay (LIA). Reactive samples in ELISA were tested for the presence of antibodies to HIV-1 group O viruses by ELISA using V3 peptides from HIV-1 ANT-70 and HIV-1 MVP-5180 followed by confirmation by LIA and a specific Western blot. Seventeen HIV-1 strains were isolated (1988-1993) and a 900 base-pair fragment encoding the env region containing V3, V4, V5 and beginning of gp41 was sequenced and a phylogenetic tree was constructed. RESULTS: HIV prevalence was relatively low and remained stable (0.7-1.6% in pregnant women, 2.1-2.2% in the general population). The prevalence was also stable among prisoners (2.1-2.6%). Among hospitalized and tuberculosis patients prevalence was higher and increased (1.8-12.7% and 1.5-16.2%, respectively). Only three sera had antibodies to HIV-1 group O. The 17 HIV-1 strains represent six different genetic subtypes including type O. CONCLUSION: Our data from 1986 to 1994 show a stable and low HIV prevalence in Gabon, and a high genetic diversity of HIV-1 strains. This, also observed in Cameroon, is in contrast to that found elsewhere in Africa. Differences in rate of spread of HIV infection are probably explained by interplay between numerous factors. The role of different HIV subtypes in the dynamics of the HIV epidemic should be examined further.

Adult↗