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Biomedical subjects

S Bonnet

Publications and source records attributed to S Bonnet.

At least 19 recordsLinked to original sources

Transstadial and transovarial persistence of Babesia divergens DNA in Ixodes ricinus ticks fed on infected blood in a new skin-feeding technique.

Although Babesia divergens is the the principal confirmed zoonotic Babesia sp. in Europe, there are gaps in our knowledge of its biology and transmission by the tick Ixodes ricinus. In order to reproduce the part of the parasite cycle that occurs in the vector, an in vitro animal skin feeding technique on blood containing in vitro cultivated B. divergens was developed. Parasite DNA was detected in all samples of salivary glands of nymphs and adults that had fed on parasitized blood as larvae and nymphs, respectively, indicating acquisition as well as a transtadial persistence of B. divergens. PCR performed on eggs and larvae produced by females that had fed on parasitized blood demonstrated the existence of a transovarial transmission of the parasite. Gorging B. divergens infected larvae on non-infected gerbils showed persistance of the parasite over moulting into the resulting nymphs. These results indicate that the parasitic stages infective for the vector (i.e. the sexual stages) can be produced in vitro. To our knowledge, this is the first report of artificial feeding of I. ricinus via membrane as well as in vitro transmission of B. divergens to its vector. The opportunities offered by the use of such a transmission model of a pathogen by I. ricinus are discussed.

Animals↗

[Malignant hereditary paraganglioma: problems raised by non-functional forms management].

Non-functional paraganglioma have not clinical or biological characteristics, so that the diagnostic is most of the time delayed and made on the occasion of advanced abdominal tumor or symptomatic metastasis management. Hereditary forms, notably those with SDHB mutation, seem to have a poor prognosis. On the other hand, and on the oposite to sporadic forms, they are the only ones to benefit from genetic testing which make possible, if positive, an earlier diagnostic, before apparition of symptoms, recurrence or metastasis. We report a case of non-functional malignant hereditary paraganglioma diagnosed belatedly and we will consider management problems raised by non-functional forms.

Abdominal Neoplasms↗

[Leiomyosarcoma of the middle segment of the inferior vena cava: tactical problems raised by renal and caval revascularisation].

INTRODUCTION: Leiomyosarcoma of the inferior vena cava is mesenchymal tumor accounting for 95% of primary tumors of the vena cava. Characteristic features include late invasion of adjacent structures and metastases, and delayed diagnosis. OBSERVATION: We report a case of inferior vena cava (IVC) leiomyosarcoma (LMS) found in a 53 year-old man who complained of abdominal pain. Morphologic exams found a very large polycyclic mass in the inferior vena cava involving the middle segment of the vena cava extending from the renal veins to the hepatic veins. An "en bloc" resection of the tumor was achieved. Caval outflow was restored using a ring-reinforced PTFE tube graft, the left renal vein was ligated and not re-implanted, the right renal vein was implanted in a lumbar sub-renal vein using a short prosthesis. Pathological examination documented a grade II leiomyosarcoma of the inferior vena cava and the patient was given adjuvant chemotherapy (anthracycline). One year later, there was no local or regional relapse. COMMENT: We emphasize the importance of restoring caval outflow which provides effective results when used with a ring-reinforced polytetrafluoroethylene (PTFE) prosthesis. Furthermore, the importance of restoring right renal outflow is highlighted because ligature of the renal vein can lead to renal ischemia and nephrectomy which should only be performed in specific cases. The tactical problems of renal and caval revascularisation, including the place of prosthetic replacement, are discussed.

Blood Vessel Prosthesis↗

cpbAg1 encodes an active carboxypeptidase B expressed in the midgut of Anopheles gambiae.

We previously used differential display to identify several Anopheles gambiae genes, whose expression in the mosquito midgut was regulated upon ingestion of Plasmodium falciparum. Here, we report the characterization of one of these genes, cpbAg1, which codes for the first zinc-carboxypeptidase B identified in An. gambiae and in any insect. Expression of cpbAg1 in baculovirus gave rise to an active enzyme, and determination of the N-terminal amino acids confirmed that CPBAg1 contains a signal peptide and a pro-peptide, typical features of digestive zinc carboxypeptidases. cpbAg1 mRNA was mainly produced in the mosquito midgut, where it accumulated in unfed females and was rapidly down-regulated upon blood feeding. Annotation of the An. gambiae genome predicts twenty-three sequences coding for zinc-carboxypeptidases of which only two (cpbAg1 and cpbAg2) are expressed at a significant level in the mosquito midgut.

Amino Acid Sequence↗

Plasmodium falciparum transmission blocking immunity under conditions of low and high endemicity in Cameroon.

Transmission blocking immunity (TBI) was studied in relation to age, gametocyte density and transmission intensity. subjects with high gametocytaemias were selected in a hypo-endemic urban district and a hyper-endemic rural area in South Cameroon. TBI was determined in blood from gametocyte carriers in a bioassay (Direct Membrane Feeding Assay), with either autologous plasma (OWN) or control serum (AB). Mosquito infection rates (IR) were compared. infection rates correlated positively with gametocyte and oocyst densities. Three TBI indicators were analysed: the proportion of transmission reducers (IRAB > IROWN, P < 0.01), the mean intensity of TBI (IRAB - IROWN), and the contribution of TBI to total inhibition [(IRAB-IROWN)/(100-IROWN)]. we could not discriminate between areas with regard to either the proportion of transmission reducers (urban 15% and rural 29%) or the mean levels of TBI (urban 10% and rural 9%), or contribution of TBI to total inhibition (urban 10% and rural 13%). there was no relationship between TBI indicators and age, but a trend of increasing values was observed with rising gametocytaemia, which was considered as a confusing factor. a multivariable analysis showed that the probability of being a reducer was 4.6 fold higher in the rural area than in the urban district.

Adolescent↗

Stage-specific effects of host plasma factors on the early sporogony of autologous Plasmodium falciparum isolates within Anopheles gambiae.

Summary Quantitatively assessing the impact of naturally occurring transmission-blocking (TB) immunity on malaria parasite sporogonic development may provide a useful interpretation of the underlying mechanisms. Here, we compare the effects of plasma derived from 23 naturally infected gametocyte carriers (OWN) with plasma from donors without previous malaria exposure (AB) on the early sporogonic development of Plasmodium falciparum in Anopheles gambiae. Reduced parasite development efficiency was associated with mosquitoes taking a blood meal mixed with the gametocyte carriers' own plasma, whereas replacing autologous plasma with non-immune resulted in the highest level of parasite survival. Seven days after an infective blood meal, 39.1% of the gametocyte carriers' plasma tested showed TB activity as only a few macrogametocytes ingested along with immune plasma ended up as ookinetes but subsequent development was blocked in the presence of immune plasma. In other experiments (60.9%), the effective number of parasites declined dramatically from one developmental stage to the next, and resulted in an infection rate that was two-fold lower in OWN than in AB infection group. These findings are in agreement with those in other reports and go further by quantitatively examining at which transition stages TB immunity exerts its action. The transitions from macrogametocytes to gamete/zygote and from gamete/zygote to ookinete were identified as main targets. However, the net contribution of host plasma factors to these interstage parasite reductions was low (5-20%), suggesting that irrespective of the host plasma factors, mosquito factors might also lower the survival level of parasites during the early sporogonic development.

Animals↗

Histone deacetylase inhibition and estrogen receptor alpha levels modulate the transcriptional activity of partial antiestrogens.

In this study, we have analysed the effects of histone deacetylase (HDAC) inhibition on estrogen receptor (ER) expression and on its transcriptional activity in response to antiestrogens. In several breast cancer cell lines, trichostatin A (TSA), a potent HDAC inhibitor, strongly decreases ERalpha expression in a dose-dependent manner. This repression is observed independently of the presence of ligand and also occurs in ovarian and endometrial cell lines. In addition, we show that in MCF7 cells bearing a stably transfected reporter plasmid (MELN cells), partial antiestrogens such as 4-OH-tamoxifen (OHTam), raloxifen or LY117018, switch to an agonist activity upon HDAC inhibition. This effect is blocked by the pure antiestrogen ICI182780 and exhibits a half-maximal concentration of OHTam equivalent to its affinity for ERalpha. The TSA-dependent decrease of ERalpha expression is required to induce the agonist switch of OHTam properties as it is lost in cells constitutively expressing exogenous receptors (MELN-ERalpha or ERbeta). By contrast, the transrepression activity of OHTam is abolished by TSA independently of the decrease of ERalpha expression. Interestingly, in MELN-ERalpha, ICI182780 remains inhibitory suggesting the involvement of HDAC-independent mechanisms. Finally, in the absence of TSA, transcriptional activity in response to OHTam is significantly raised in MELN cells expressing low levels of ERalpha after transfection of antisense oligonucleotides. In conclusion, inhibition of HDAC enzymatic activity and modulation of ERalpha levels tightly control the relative agonist activity of partial antiestrogens on a stably integrated reporter transgene.

Breast Neoplasms↗

Body motion capture for activity monitoring.

CEA-LETI has developed a 3D orientation tracker based on accelerometers and magnetometers. Owing to an efficient data fusion algorithm, the tracker provides accurate 3D orientation angles. The tracker is small enough to be used as a wearable device and therefore is an interesting tool for body motion capture. Investigations are being performed to analyse how activity of a person can be monitored from body motion measured with the tracker. In the domain of healthcare monitoring, many applications are envisaged such as rehabilitation with 3D body motion capture, elderly dependency evaluation, context acquisition for physiological monitoring.

Activities of Daily Living↗

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↗