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Biomedical subjects

S Bonnet

Publications and source records attributed to S Bonnet.

At least 19 recordsLinked to original sources

Level and dynamics of malaria transmission and morbidity in an equatorial area of South Cameroon.

We conducted parasitological and entomological malaria surveys among the population of Mengang district in southern Cameroon to analyse the relationship between malaria transmission intensity and malaria morbidity. We investigated two adjacent areas which differ 10-fold in transmission intensity [annual entomological inoculation rate (EIR) 17 vs. 170], but have very similar Plasmodium falciparum malariometric profiles with parasite prevalences of 58 vs. 64%, high parasitaemia prevalences (> 1000 parasites/microl) of 15 vs. 16% and the same morbidity of 0.17-0.5 attacks/person/year. Plasmodium malariae prevalence was 14 vs. 16%. One possible explanation is that the similarity of the duration of the short and high transmission seasons in both areas is equally, if not more, significant for parasitological and clinical profiles as the annual EIR. We discuss the relationships between variations in transmission levels, parasitaemia and clinical incidence, and draw parallels to similar situations elsewhere.

Adolescent↗

[Cause of unusual unilateral vitreous hemorrhage: neuroretinitis of Cat-Scratch disease. Presentation of a case].

A 49 years old woman presents an unilateral decrease of vision. An important vitreous hemorrhage obscures the fundus. After partial resorption a typical aspect of neuroretinitis is seen: macular and disc edema with macular star formation. Cat-Scratch disease is suspected after general examination of the patient. This diagnosis will be confirmed by the laboratory investigation. This disease is not so rare and represents one of the principal causes of neuroretinitis. The vitreous hemorrhage can be due to vascular insult by the bacterium responsible for Cat-Scratch disease which one has an important tropism for endothelial cells and can be responsible for vascular occlusive phenomena. Clinical signs, treatment and evolution of this disease are going to be discussed in this article.

Cat-Scratch Disease↗

[Macro-CK disclosing disseminated epidermoid carcinoma of the pyriform sinus in a patient with dermatomyositis].

INTRODUCTION: The association between dermatomyositis and cancer is clearly established, but its frequency remains difficult to define. EXEGESIS: We report the case of an association between a dermatomyositis and a cancer of the piriform antrum. Four months after surgical treatment and radiotherapy, the increased macro-CK level gave us reason to suspect a cancer relapse with pulmonary, hepatic, splenic and renal metastases without progressive clinical signs. CONCLUSION: Mitochondrial macro-CK detection must evoke the presence of neoplasia with or without metastasis, which would be a poor prognosis, as has been shown in our patient.

Carcinoma, Squamous Cell↗

Transcripts of the malaria vector Anopheles gambiae that are differentially regulated in the midgut upon exposure to invasive stages of Plasmodium falciparum.

Understanding the interactions between the most deadly malaria parasite, Plasmodium falciparum, and its main vector, Anopheles gambiae, would be of great help in developing new malaria control strategies. The malaria parasite undergoes several developmental transitions in the mosquito midgut and suffers population losses to which mosquito factors presumably contribute. To identify such factors, we analysed An. gambiae midgut transcripts whose expression is regulated upon ingestion of invasive or non-invasive forms of P. falciparum using a differential display approach. Sixteen cDNA were studied in detail; 12 represent novel genes of An. gambiae including a gene encoding profilin. Four transcripts were specifically regulated by P. falciparum gametocytes (invasive forms), whereas the others were regulated by either non-invasive or both non-invasive and invasive forms of the parasite. This differential regulation of some genes may reflect the adaptation of P. falciparum to its natural vector. These genes may be involved in the development of P. falciparum in An. gambiae or in the defence reaction of the mosquito midgut towards the parasite.

Animals↗

Chronic hypoxia-induced spontaneous and rhythmic contractions in the rat main pulmonary artery.

The effect of chronic hypoxia (CH; 1-4 wk) on the electromechanical properties of the rat main pulmonary artery (MPA) was investigated. MPA rings obtained from rats exposed for 14 days to hypobaric (50.5 kPa) CH exhibited spontaneous and rhythmic contractions (SRCs) that were never observed in control (normoxic) rats. SRCs were unaffected by tetrodotoxin, phentolamine, BQ-123 and BQ-788, N-nitro-L-arginine methyl ester, or endothelium removal. CH depolarized smooth muscle cells from -58.8 +/- 9 to -38.6 +/- 5.4 mV and increased the resting cytosolic Ca2+ concentration from 67.3 +/- 11.9 to 112.5 +/- 16.4 nM. CH also induced spontaneous spikelike depolarizations. All of these effects were inhibited by external Ca2+ removal or nifedipine (1 microM). Moreover, depletion of intracellular Ca2+ stores with ryanodine (1-5 microM) or cyclopiazonic acid (3 microM) progressively attenuated SRCs. This study demonstrates that CH switches the MPA from a quiescent to a spontaneously active mechanical state. Finally, the fact that SRCs precede the development of right ventricle hypertrophy and disappear when this hypertrophy reaches a maximal value (after 3-4 wk of CH) suggests that SRCs may play a role in the adaptive process of the pulmonary circulation to CH.

Animals↗

Effect of chronic hypoxia on agonist-induced tone and calcium signaling in rat pulmonary artery.

The effect of chronic hypoxia (CH) for 14 days on Ca2+ signaling and contraction induced by agonists in the rat main pulmonary artery (MPA) was investigated. In MPA myocytes obtained from control (normoxic) rats, endothelin (ET)-1, angiotensin II (ANG II), and ATP induced oscillations in intracellular Ca2+ concentration ([Ca2+]i) in 85-90% of cells, whereas they disappeared in myocytes from chronically hypoxic rats together with a decrease in the percentage of responding cells. However, both the amount of mobilized Ca2+ and the sources of Ca2+ implicated in the agonist-induced response were not changed. Analysis of the transient caffeine-induced [Ca2+]i response revealed that recovery of the resting [Ca2+]i value was delayed in myocytes from chronically hypoxic rats. The maximal contraction induced by ET-1 or ANG II in MPA rings from chronically hypoxic rats was decreased by 30% compared with control values. Moreover, the D-600- and thapsigargin-resistant component of contraction was decreased by 40% in chronically hypoxic rats. These data indicate that CH alters pulmonary arterial reactivity as a consequence of an effect on both Ca2+ signaling and Ca2+ sensitivity of the contractile apparatus. A Ca2+ reuptake mechanism appears as a CH-sensitive phenomenon that may account for the main effect of CH on Ca2+ signaling.

Adenosine Triphosphate↗

[Grave complications of local anesthesia for cataract extraction: reports of 8 cases].

Cataract extraction performed under local anesthesia is not so safe. During a 2 years period, 8 patients have presented a complication: 3 patients are presented with diplopia, 4 patients are presented with eyeball perforation and 1 patient developed a central complication. All those complications are caused by the superior peribulbar injections of anesthetics. A survey of the different etiologies of the superior rectus muscle blow and of eyeball perforation is given.

Adult↗

[Molecular genetics of pigmentary retinopathies: identification of mutations in CHM, RDS, RHO, RPE65, USH2A and XLRS1 genes].

PURPOSE: To evaluate the occurrence and inheritance of various types of pigmentary retinopathy in patients followed at the outpatient clinic in the university hospital, Montpellier, France. To characterize genes and mutations causing these conditions. METHODS: Ophthalmic examination and various visual tests were performed. Mutations were sought from genomic DNA by PCR amplification of exons associated with single-strand conformation analysis and/or direct sequencing. RESULTS: Among 315 patients over an 8-year period, cases of retinitis pigmentosa (63.2%), Usher's syndrome (10.2%), Stargardt's disease (5.4%), choroideremia (3.2%), Leber's congenital amaurosis (3.2%), congenital stationary night blindness (2.9%), cone dystrophy (2.5%), dominant optic atrophy (1.9%), X-linked juvenile retinoschisis (1.6%), Best's disease (1.6%), and others (4.3%) were diagnosed. In retinitis pigmentosa, inheritance could be determined in 54.2% of the cases including dominant autosomic (26.6%), recessive autosomic (22.6%), and X-linked cases (5%) while it could not be confirmed in 45.7% of the cases (simplex cases in the majority). For the 6 examined genes, mutations were found in 22 out of 182 propositus (12.1%). Analysis of phenotype-genotype correlations indicates that in retinitis pigmentosa, RDS is more frequently associated with macular involvement and retinal flecks, RHO with regional disease, and RPE65 with the great severity of the disease with some cases of Leber's congenital amaurosis. CONCLUSIONS: Identification of genes may help in diagnosis and in genetic counseling, especially in simplex cases with retinitis pigmentosa. In this latter condition, molecular diagnosis will be necessary to rationalize future treatments.

Adaptor Proteins, Signal Transducing↗

Estrogen receptor cofactors expression in breast and endometrial human cancer cells.

In order to approach the molecular basis of the tissue-specific agonistic activity of antioestrogens, we have compared, at the mRNA level, the expression of various transcriptional cofactors (activators or repressors) of estrogen receptors in different breast (MCF7, ZR75-1, T47D, MDA-MB231) and endometrial (Ishikawa, RL-95-2 and HEC1A) human cancer cell lines. We showed that for SRC-1, CBP, TIF1alpha, RIP140, N-CoR, and SMRT, no significant differences in the expression levels were observed between breast and endometrial cells. For TIF1alpha mRNA, both isoforms were also detected at similar levels in all the cells tested. By contrast, over-expression of AIB1 mRNA was observed in MCF7 cells, but not in other breast or endometrial cells, irrespective of their ER-status. We then used protein-protein interaction assay (far-Western blot) to confirm the increased expression of at least one of the p160 proteins in MCF7 cells. Finally, we demonstrated that RIP140 mRNA is directly induced by estrogens in ER-positive MCF7 breast cancer cell lines but not in Ishikawa endometrial cells. Together these results indicate that some differences exist between breast and endometrial cancer cell lines at the level of estrogen receptor transcription cofactor expression.

Adaptor Proteins, Signal Transducing↗

The use of anti-Pfs 25 monoclonal antibody for early determination of Plasmodium falciparum oocyst infections in Anopheles gambiae: comparison with the current technique of direct microscopic diagnosis.

Experimental infections of laboratory-reared anopheline mosquitoes were carried out with 57 Plasmodium falciparum gametocyte carriers from Cameroon. Prevalence of infected mosquitoes and oocyst intensity were determined by two independent methods. Young P. falciparum oocysts were detected on day 2 after feeding using an immunofluorescent assay, and the results were compared with direct microscopic examination of midgut oocysts on day 7 postinfection. The immunofluorescent assay was based on a FITC-labeled anti-25-kDa monoclonal antibody, while the direct microscopy was performed on midguts stained with 2% mercurochrome. Young oocysts were easily detected by their typical and bright green-fluorescing Pfs25 positive coat and their characteristic pattern of pigment granules under transmitted white light examination. The agreement between the results of the two methods was assessed using the Kappa coefficient on prevalences of positive infections and the interclass correlation coefficient on arithmetic mean oocyst load per infected midgut. The results indicated a low agreement between the two methods for the comparison of prevalences of infected mosquitoes. However, this agreement was near perfect for the comparison of mean oocyst intensities. Prevalences of positive infections and the overall number of parasites per positive gut were significantly correlated for both methods. Thus, the immunofluorescent test could be an appropriate tool for early determination of malaria infection in mosquitoes, particularly under laboratory conditions. The possible applications of this immuno-fluorescent technique are discussed.

Animals↗

Radiation-induced changes in nucleotide metabolism of two colon cancer cell lines with different radiosensitivities.

PURPOSE: To investigate changes in nucleotide metabolism after irradiation. MATERIALS AND METHODS: HT29 and SW48 human colon carcinoma cells were exposed to 60Co gamma-rays at doses ranging from 0 to 7.5 Gy. At different times after irradiation, the activities of nine enzymes involved in nucleotide metabolism were measured, the levels of thymidine kinase and deoxycytidine kinase proteins were evaluated by Western blot, and cell-cycle kinetics were analysed by flow cytometry. RESULTS: Changes in enzyme activities concerned not purine but pyrimidine metabolism and essentially the salvage pathway for deoxyribonucleotide synthesis. They were greater in the less radiosensitive HT29 cells. The levels of thymidine kinase and deoxycytidine kinase proteins changed in parallel with their activities. The metabolic changes in irradiated cells did not seem to be due to S-phase transition and the pattern of enzyme activity changes was different from that observed in proliferative cells. CONCLUSIONS: Radiation-induced changes in the salvage pathway for pyrimidine deoxyribonucleotide synthesis were observed. These findings could be exploited in cancer therapy because higher enzyme activities after irradiation suggest that radiation exposure may render cells more sensitive to the drugs activated by these enzymes.

Cell Cycle↗

Effect of ligand and DNA binding on the interaction between human transcription intermediary factor 1alpha and estrogen receptors.

Hormonal regulation of gene activity is mediated by nuclear receptors acting as ligand-activated transcription factors. To achieve efficient regulation of gene expression, these receptors must interact with different type of molecules: 1) the steroid hormone, 2) the DNA response element, and 3) various proteins acting as transcriptional cofactors. In the present study, we have investigated how ligand and DNA binding influence the in vitro interaction between estrogen receptors (ERs) and the transcription intermediary factor hTIF1alpha (human transcriptional intermediary factor 1alpha). We first optimized conditions for the coactivator-dependent receptor ligand assay to lower ED50, and we then analyzed the ability of various natural and synthetic estrogens to allow the binding of the two types of proteins. Results were compared with the respective affinities of these ligands for the receptor. We then developed a protein-protein-DNA assay allowing the quantification of cofactor-ER-estrogen response element (ERE) complex formation in the presence of ligand and used measurements of fluorescence anisotropy to define the equilibrium binding parameters of the interaction. We demonstrated that the leucine-charged domain of hTIF1alpha is sufficient to interact with ERE-bound ERalpha in a ligand-dependent manner and showed that binding of ERalpha onto DNA does not significantly affect its hormone-dependent association with TIF1alpha. Finally, we show that, mainly in the absence of hormone, hTIF1alpha interacts better with ERbeta than with ERalpha independently of the presence of ERE.

Binding Sites↗

[Preservation of the native aortic valve in the treatment of aortic aneurysmal dilatation].

Mechanical valve conduit replacement of the aortic root is a durable and appropriate procedure for aortic root dilatation with or without aortic aortic insufficiency. But this procedure may sacrifice an anatomically salvageable aortic valve and requires a life-long anticoagulation with its attendant thromboembolic versus haemorrhagic risks, which is not ideal for young active patients. Recently, two techniques of aortic root replacement with aortic valve sparing have been described, based on experimental data. The first one is Yacoub's procedure (1983), where the correction of the aortic root is performed by correcting the sinotubular junction and replacement of the aortic sinuses with an appropriately tailored Dacron graft (remodelling). The second technique was described by David (1992). In this one, the aortic root reconstruction is performed by reimplanting the aortic valve in a tubular Dacron graft (reimplantation). Since 1993, we have been interested in these procedures and the aim of this study was to examine the perioperative and intermediate term results of these techniques. From 1993 to 1998, 14 patients had either reimplantation of the aortic valve (3 patients) or remodelling of the aortic root (11 patients). Patients' ages ranged from 17 to 57 years (40.2 +/- 7.9 years). Four patients had Marfan's syndrome (29%). There were 11 cases of aortic insufficiency, three 1+ (21.4%), 3+ (21.4%), seven 2+ (50%) and one 3+ (7.2%). All the patients had morphologically normal aortic leaflets. The mean diameter of the sinuses was 57 +/- 4 mm. There was no acute or chronic dissection. The left ventricular function was measured as the percentage of the fractional shortening of the left ventricular diameter. The mean of the fractional shortening was 38.3 +/- 4%. There was no mortality and all patients underwent early and late follow-up echocardiography. The 14 patients have only mild or no insufficiency, which has not progressed in any patient. No other valve-related complication has occurred. Aortic valve-sparing replacement of the aortic root is an excellent procedure for patients with aortic root dilatation and anatomically salvageable valves. The long-term results are still unknown but it seems an attractive alternative to composite replacement of the aortic valve and descending aorta. Morbidity and mortality rates are very low, even lower than a Bentall procedure, while the savings in cost and human lives due to the absence of a mechanical valve prosthesis are significant.

Adolescent↗

Efficient reamplification of differential display products by transient ligation and thermal asymmetric PCR.

A new method for specific reamplification of DDRT-PCR products is presented. After transient ligation of the primary DDRT-PCR fragments into a T-vector, the cDNAs of interest were reamplified by hemi-nested PCR and thermally asymmetric cycles. In contrast to the originally described protocol, this method of reamplification is specific, sensitive, reproducibly gives a high yield of DNA and allows direct sequencing of the reamplified product without purification or cloning.

Animals↗

[Levels of malaria transmission: methods and parameters].

Evaluation of malaria transmission levels is necessary to compare ecologically diverse areas and to assess the effectiveness of efforts to control the disease. The purpose of this report is to describe useful techniques for descriptive epidemiology and potentially pertinent indicators regarding the three links in the epidemiological chain: transmission from mosquito to man, transmission from man to mosquito, and sporogonic cycle. Standards for evaluation of transmission from mosquito to man are now well established. Techniques and resulting data, mostly entomological, have been validated in numerous multicenter and multidiscipline studies before and after implementation of control measurements. Evaluation of transmission from man to mosquito has not yet been extensively studied. Gametocyte index does not appear to be a good indicator of infectivity in mosquitoes. Two other parameters that have been proposed in the literature are rate of human infectivity to mosquitoes and probability that a bloodmeal will be infectious. However these evaluation techniques have been neither subjected to comparative study nor validated in epidemiological surveys. The third factor for evaluation of malaria transmission levels involves sexual development of the gametocytes (sporogonic cycle) in the vector. Two indicators that might be useful in this regard are quantification of early-stage parasites in the stomach of the mosquito and study of blood factors in subjects in whom inhibition transmission has been documented. Since these methods have been used only sporadically, further study will be needed to validate this approach to evaluate transmission level.

Animals↗

Coloboma, mental retardation, hypogonadism, and obesity: critical review of the so-called Biemond syndrome type 2, updated nosology, and delineation of three "new" syndromes.

Biemond syndrome type 2 (BS2) is classically regarded as a recessively inherited condition (MIM 210350) comprising mental retardation, coloboma, obesity, polydactyly, hypogonadism, hydrocephalus, and facial dysostosis. Clinically, the disorder is closely related to Bardet-Biedl syndrome. Few cases have been reported, most of them before 1970. We present clinical data on three mentally retarded sporadic cases with coloboma, obesity, and hypogenitalism (in two of them), fitting as first glance a diagnosis of BS2. A review documents striking clinical variability among the patients said to have BS2. We propose a new nosology of those cases and delineate several new clinical forms. Purported BS2 cases may be divided into: (1) Bardet-Biedl syndrome with fortuitous coloboma or aniridia, (2) BS2 sensu stricto, a recessively inherited syndrome of sexual infantilism, short stature, coloboma, and preaxial polydactyly without obesity, only known from the original report, (3) a "new" dominantly inherited form of colobomatous microphthalmia occasionally associated with obesity, hypogonadism, and mental retardation, to which our observations belong. (4) cytogenetically proven Rubinstein-Taybi syndrome (one case), (5) an unclassifiable, early lethal familial syndrome resembling Buntinx-Majewski syndrome, and (6) a "new" coloboma-zygodactyly-clefting syndrome. The latter two syndromes may result from chromosomal anomaly.

Abnormalities, Multiple↗

Both estradiol and tamoxifen decrease proliferation and invasiveness of cancer cells transfected with a mutated estrogen receptor.

Previous studies have shown that, after wild-type estrogen receptor (ER) transfection in ER-negative breast cancer cells, estradiol but not tamoxifen prevents growth, invasiveness and metastasis of these cells in mice. Because an ER mutation at position 400 converts the triphenylethylene antiestrogen, OH-tamoxifen into a full estrogen agonist, we transfected this mutated form of human ER in an ER-negative rat cancer cell line. This was aimed at inducing an inhibitory, estrogen-like response of tamoxifen in these cells. In two stable ER-positive transfectants, OH-tamoxifen inhibited cell growth and invasiveness in vitro as efficiently as estradiol. The pure antiestrogen, ICI 164,384, was not agonistic alone and antagonized estrogen action. In contrast, the three compounds were ineffective in control mock-transfected cells. When injected into ovariectomized nude mice, ER-negative mock-transfected cells formed tumours which were significantly stimulated by estradiol and inhibited by tamoxifen treatment. This indicates that estradiol and tamoxifen altered the growth of ER-negative tumours via a general effect on the host response. Surprisingly, the hormone responsiveness of ER-positive tumours developed from ER-transfected cells did not significantly differ from that of ER-negative (mock-transfected) tumours. We conclude that transfection of a mutated human estrogen receptor inhibited, through an estrogenic activity of tamoxifen, the growth and invasiveness of these cancer cells in vitro. However, the low expression of ER did not allowed us to obtain the same effect of tamoxifen in vivo.

Animals↗