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Biomedical subjects

A Bonnin

Publications and source records attributed to A Bonnin.

At least 19 recordsLinked to original sources

Reduced fungal contamination of the indoor environment with the Plasmair system (Airinspace).

Aspergillus spp. and other moulds cause life-threatening opportunistic infections in immunocompromised patients. Indoor contamination and construction work that liberate fungal spores are a major source of nosocomial aspergillosis. Dijon hospital is a tertiary care institution in northeast France undergoing construction work beside high-risk clinical units. To determine the impact of this activity, a surveillance programme was implemented one year before building work began in order to establish baseline levels of contamination. Air and surface fungal contamination in adult and paediatric haematology units were prospectively examined following use, or not, of a new air-treatment system with mobile Plasmair units (Airinspace). There were significant reductions in overall fungal contamination for the Plasmair treated rooms for air and surface samples in both clinical units. Plasmair treatment also significantly reduced A. fumigatus in the air. These data suggest that Plasmair units may provide an efficient method of reducing indoor fungal contamination in hospitals.

Air Microbiology↗

Expression mapping of 5-HT1 serotonin receptor subtypes during fetal and early postnatal mouse forebrain development.

Serotonin (5-HT) is implicated in several aspects of brain development, yet the ontogenetic expression patterns of 5-HT receptors responsible for transducing specific effects have largely not been characterized. Fifteen different 5-HT receptor genes have been cloned; therefore any spatial and/or temporal combination of their developmental expression could mediate a wide array of 5-HT effects. We undertook a detailed analysis of expression mapping of the Gi/o-coupled 5-HT1 (5-HT1A, 1B, 1D and 1F) receptor subtypes in the fetal and early postnatal mouse forebrain. Using receptor subtype-specific riboprobes and in situ hybridization, we observed that all 5-HT1 receptor subtypes are expressed as early as embryonic day (E) 14.5 in the forebrain, typically in gradients within specific structures. Among 5-HT1 receptors, the 5-HT1A receptor transcript is expressed densely in E14.5-16.5 thalamus, in hippocampus, and in a medial to lateral gradient in cortex, whereas the 5-HT1B receptor mRNA is expressed in more lateral parts of the dorsal thalamus and in the striatum at these ages. The 5-HT1D receptor transcript, which also is expressed heavily in E14.5-E16.5 thalamus, appears to be down-regulated at birth. The 5-HT1F receptor transcript is present in proliferative regions such as the cortical ventricular zone, ganglionic eminences, and medial aspects of the thalamus at E14.5-16.5, and otherwise presents similarities to the expression patterns of 5-HT1B and 1D receptor transcripts. Overall, the 5-HT1 subfamily of Gi/o-coupled 5-HT receptors displays specific and dynamic expression patterns during embryonic forebrain development. Moreover, all members of the 5-HT1 receptor class are strongly and transiently expressed in the embryonic dorsal thalamus, which suggests a potential role for serotonin in early thalamic development.

Age Factors↗

In vitro susceptibility testing of Candida and Aspergillus spp. to voriconazole and other antifungal agents using Etest: results of a French multicentre study.

Minimum inhibitory concentrations (MICs) of the antifungal agent voriconazole were determined using the Etest and compared with those of amphotericin B, itraconazole and fluconazole using 1986 clinical isolates of Candida spp. Voriconazole MICs were also compared with those of amphotericin B and itraconazole using 391 clinical isolates of Aspergillus spp. Voriconazole was found to have more potent activity and lower MIC values than amphotericin B, itraconazole and fluconazole against C. albicans, C. tropicalis, C. parapsilosis and C. kefyr. Against C. glabrata and C. krusei, voriconazole was more active than either of the other two azole antifungals but had similar activity to amphotericin B. For species of Aspergillus, MIC values of voriconazole were lower than those of amphotericin B and itraconazole against A. fumigatus and A. flavus, and were similar to those of amphotericin B against A. niger. Against A. terreus, MIC values for voriconazole and itraconazole were similar. A. terreus is known to be resistant to amphotericin B, and this was reflected in higher MIC values compared with those of voriconazole and itraconazole. Voriconazole therefore compares very favourably with other antifungal agents against a large number of clinical isolates of Candida and Aspergillus spp.

Amphotericin B↗

The French language virtual medical university.

The work program of the French Language Virtual Medical University started about 2 years ago, and entered into a real active phase of development and implementation in 2002. Various national programs and organizational initiatives should accelerate and facilitate further appropriation of modem pedagogical approaches by knowledge providers and all users of the FSVMU, so as to advance on the way of virtual education. The French Language Virtual Medical University under the auspices of both the National Conference of Deans of Medical Schools and the International Conference of Deans of French-Speaking Medical Schools has been developed to create a major Internet portal for French-speaking distance medical learning and teaching. This construct should be representative of all medical schools in France and French-speaking countries. Contents will also be translated into English, Spanish and Arabic. All medical disciplines with their various levels of teaching are to be included. Cross-related fields are also going to be present in order to offer full range programs. The latter are intended to provide both initial and continuing education for medical students as well as all other categories of health professionals and medical and scientific research workers. To develop the appropriate technology and make such a portal, on one hand correspond to the specific educational requirements and proper training for health professionals, and on the other hand provide a general access to e-learning in all schools of medicine; in keeping with such goals, the following approaches should be stressed upon. To build a virtual space where individual patients, their families, patient associations as well as the general public, can obtain medical information of good quality for the purposes of both education and prevention. Providing such categories with reliable and validated sources of information, and offering an ethical basis for the increasing practice of e-medicine, represent in today's and tomorrow's world one of the great modern challenges for the medical community. Beyond the sole medical domain, the model offered by the FSVMU should be useful for the French-speaking Universities in all the fields of knowledge and training which are candidate to benefit from new educational means and methods.

Computer Simulation↗

False-positive results caused by cotton swabs in commercial Aspergillus antigen latex agglutination test.

While testing for Aspergillus spp. using a commercially available latex agglutination test on a brain biopsy wrapped in a cotton swab, false-positive results were obtained. Subsequent application of the test on lavage samples obtained using cotton and synthetic swabs resulted positive with the cotton swabs only. This suggests that epitopes cross-reactive with Aspergillus galactomannan may be present in cotton.

Antigens, Fungal↗

Design, characterization and preclinical efficacy of a cationic lipid adjuvant for influenza split vaccine.

We prepared a series of cationic lipid vesicles comprising a cationic cholesterol derivative, DC-Chol with or without a neutral phospholipid, DOPC or DOPE. The vesicles were tested for their ability to bind and adjuvant split inactivated influenza vaccines. We found that DC-Chol-containing liposomes are capable to strongly bind influenza vaccine antigens upon simple mixing with the vaccine. The resulting formulations induced robust anti-influenza immune responses both after s.c. and i.n. administration in BALB/c mice while neutral Cholesterol/DOPC liposomes displayed virtually no stable antigen binding and no adjuvant effect. The parenteral adjuvant effect of DC-Chol on trivalent split influenza vaccines was then confirmed in outbred mice and monkeys. Among the most potent formulations tested, a simple mixture of the vaccine with a microfluidized dispersion of DC-Chol in an aqueous buffer is being considered for further development to produce an improved influenza vaccine.

Adjuvants, Immunologic↗

Characterization of a monoclonal antibody reacting with antigen-4 domain of gp900 in Cryptosporidium parvum invasive stages.

Cryptosporidium parvum (Protozoa, Apicomplexa) infects the apical surface of intestinal epithelial cells, where it grows and divides within a membrane-bound parasitophorous vacuole. gp900, an abundant glycoprotein of C. parvum merozoites and sporozoites, is localized in micronemes and at the surface of invasive stages and participates in the invasion process. Here, we describe a new monoclonal antibody (mAb) against gp900. As shown by immunofluorescence of excysted parasites and immunoelectron microscopy of infected tissues, the mAb reacted with micronemes present in the apical pole of invasive stages. In immunoprecipitation experiments, the mAb was shown to react with a high molecular weight antigen co-migrating with gp900. Finally, three reactive clones were selected upon screening of a C. parvum genomic expression library with the mAb; and sequencing of the insert from one of them showed a 596 bp sequence identical to the DNA region encoding a domain of gp900 identified as antigen 4.

Animals↗

Decrease in Candida albicans strains with reduced susceptibility to fluconazole following changes in prescribing policies.

This study was undertaken to identify prescribing policies likely to favour or limit fluconazole resistance within a clinical department. Fluconazole exposure within the infectious diseases and clinical haematology units was investigated, and data were compared with in vitro susceptibility of Candida albicans isolates obtained in these units. Fluconazole utilization was determined by the number of fluconazole treatment-days per 100 hospitalization days (penetration index). In the infectious diseases unit, separate evaluations for low-dose fluconazole (50 mg) prescribed as intermittent or prolonged treatment, and for higher-dosing schedules (fluconazole 200 mg) were made. Susceptibility of C. albicans isolates was surveyed in a broth microdilution assay by measuring the inhibitory concentration 50% (IC50). The penetration index (PI) for fluconazole 50mg declined from 1992 to 1977 in infectious diseases (P= 0.0048). In the meantime, total usage of fluconazole increased, due to increased prescribing of fluconazole 200 mg (P = 0.0724). The IC50 of C. albicans isolates tested in infectious diseases decreased between 1994 and 1996 from 7.33 mg/ml to 1.64 mg/ml (P = 0.0075). In clinical haematology, declines in C. albicans IC50 and fluconazole PI were not significant (P = 0.35 and P = 0.07, respectively). These data suggest that prolonged or repeated exposure to low-dose fluconazole, rather than total cumulative use, was associated with fluconazole resistance in the infectious diseases unit. Moreover, restoration of a normal ecology was observed when low-dose prolonged or intermittent prescriptions were reduced.

Analysis of Variance↗

[Value of high frequency (20mhZ) and doppler ultrasound in the diagnosis of pigmented cutaneous tumors].

PURPOSE: Diagnosis of pigmented skin tumors is often difficult. The aim of the present study is to evaluate high frequency ultrasound and Doppler ultrasound in the localization and the characterization of these tumors. MATERIAL AND METHODS: One hundred and seventy six pigmented skin tumors including melanocytic and non melanocytic, benign and malignant lesions have been examined before resection using high frequency ultrasound (20MHz probe) and Doppler ultrasound (13MHz probe-Doppler frequency: 7MHz). Imaging data have been correlated with histological data, available in all cases. RESULTS: Tumors seen at ultrasound were hypoechoic lesions, some of which, particularly malignant melanocytic tumors were vascularized. Precise ultrasonographic location of the tumor was correlated to its histological location: epidermis for purely epidermal proliferations (seborrheic keratoses), superficial dermis for dermal proliferations originating from epidermis (benign dermal nevi, melanomas during vertical growth phase, basal cell carcinomas), middle and deep dermis for dermal proliferations originating from dermis (fibrous histiocytomas, angiomas). CONCLUSION: Ultrasound may help in assessing positive and differential diagnosis of pigmented skin tumors as it precises, before histological examination, the exact location of the lesion within the different skin layers and its origin. As far as malignant melanocytic tumors are concerned, high frequency ultrasound and Doppler ultrasound appear promising in diagnosis algorithm and pronosic of these lesions.

Adolescent↗

Effects of physical training on functional activity of 5-HT1B receptors in rat central nervous system: role of 5-HT-moduline.

The effect of physical exercise was examined on the sensitivity of 5-HT1B receptors and on 5-HT-moduline tissue concentration in the central nervous system of rats. Rats were trained for 7 consecutive weeks to run on a treadmill. Three groups of animals were selected: group 1, sedentary rats (controls); group 2, animals running for 1 h at 18 m/min for 5 days per week (moderate training) and group 3, animals running for 2 h, at 30 m/min on a 7% grade for 5 days per week (intensive training). The animals were sacrificed 24 h after the last running. Rat brains were dissected out to obtain hippocampus and substantia nigra and kept at -80 degrees C until use. 5-HT1B receptor activity was determined by studying [35S]GTPgammaS binding in a substantia nigra membrane preparation from individual animals, after stimulation by a selective 5-HT1B receptor agonist (CP 93,129). 5-HT-moduline tissue content in hippocampus from individual animals was determined by ELISA using a polyclonal anti-5-HT-moduline antibody. In moderately trained animals (n=5), the CP 93,129-stimulated [35S]GTPgammaS binding curve was shifted to the right compared with controls (n=6), whereas the binding was totally suppressed in intensely trained animals (n=5). In parallel, 5-HT-moduline tissue concentration in the hippocampus was slightly increased in moderately trained animals (117.3 +/- 8.9%) (n=5), whereas it was significantly increased in intensely trained animals (182.6 +/- 29.5%) (n=5) compared to controls (100 +/- 6.11%) (n=6). These results show that 5-HT1B receptors are slightly desensitized in moderately trained animals and totally desensitized in intensely trained animals; moreover, they suggest that the observed desensitization is related to an increase of 5-HT-moduline tissue content; this mechanism may play a role in various pathophysiological conditions.

Animals↗

Ultrasonic waves propagation in absorbing thin plates application to paper characterization.

Guided wave theory is applied to a thin orthotropic and absorbing plate for low frequency propagation of ultrasonic waves. The aim of this paper is to give some physical interpretations of the non-destructive characterization of paper materials, which are cellulosic fibrous networks. It is shown that the propagation problem reduces to two normal modes of propagation in the plane of the plate. Each of them depends on four complex and independent stiffnesses that are combinations of elementary complex stiffnesses of the media. The imaginary part of these stiffnesses corresponds to a possible mechanism of energy dissipation during the wave propagation for this kind of material. The reverse problem, which gives four complex values, is then numerically solved using a small attenuation assumption. The specially designed experimental set-up has led to the first measurements of tracing paper damping factors. The phase velocity measurements of the plate waves agree with the results already found by several paper researchers. As a particular and new result, the shear wave velocities are found to present a quasi-isotropic repartition in the plane of the paper sheet. It was found that the absorbing phenomenon can occur for each propagation mode in such a material. The attenuation values are small, except for one of them that corresponds to a coupling term in the propagation model. The anisotropy of their repartition is also shown in the case of quasi-longitudinal waves.

Cellulose↗

Comparative genotyping of Candida albicans bloodstream and nonbloodstream isolates at a polymorphic microsatellite locus.

Molecular typing studies have shown that the predominant form of reproduction of Candida albicans is clonal and that, in a majority of situations, persistent or recurrent infections are due to a unique strain. Characterization of distinct subpopulations and correlation with clinical features may thus be important to understanding the pathogenesis of candidiasis. In a clonal model, a unique polymorphic marker may identify populations with different biological properties. We therefore compared 48 bloodstream isolates and 48 nonbloodstream matched strains of C. albicans at the elongation factor 3-encoding gene (CEF3) polymorphic microsatellite locus of C. albicans. Sizing of the alleles was performed by automated capillary electrophoresis. A new, 137-bp allele was characterized, and seven nondescribed combinations were observed, resulting in 15 and 11 distinct CEF3 profiles in bloodstream and control strains, respectively. Genotypes 126-135, 130-136, and 131-131 accounted for 60.4% of both bloodstream and control strains. Four bloodstream isolates but no control strains displayed the 135-135 combination. None of the other genotypes was present at an increased frequency in bloodstream isolates. Bloodstream and nonbloodstream strains of C. albicans thus have a heterogeneous structure at the CEF3 locus, with three major and multiple minor allelic combinations.

Alleles↗

A single tyrosine prevents insertion of ribonucleotides in the eukaryotic-type phi29 DNA polymerase.

Three conserved motifs (named A, B and C) have been proposed to form the polymerization active site in all classes of DNA-dependent polymerases. In eukaryotic-type (alpha-like) DNA polymerases, motif A is characterized by the consensus "Dx2SLYP". Mutants in phi29 DNA polymerase residue Tyr254 of this conserved motif had been previously shown to be affected in dNTP binding. Here, we show that a single substitution of Tyr254 into a valine residue enables the enzyme to incorporate ribonucleotide substrates, without affecting its wild-type affinity for dNTPs. Whereas the wild-type enzyme preferred dNTPs more than two million-fold over rNTPs, the mutation of Tyr254 into valine reduced the discrimination for rNTPs up to 1000-fold. In addition to this discrimination mechanism, based on sugar selection, phi29 DNA polymerase is very inefficient when extending an RNA primer terminus, allowing its exonucleolytic degradation. These results indicate that the Tyr254 of phi29 DNA polymerase is responsible for the discrimination against the 2'-OH group of an incoming ribonucleotide. This is the first time that the invariant tyrosine residue of motif A is involved in ribo- versus deoxyribonucleotide discrimination in an eukaryotic-type DNA polymerase.

Bacteriophages↗

Acute stress induces a differential increase of 5-HT-moduline (LSAL) tissue content in various rat brain areas.

5-HT-moduline is an endogenous cerebral tetrapeptide (LSAL) which specifically interacts as an allosteric modulator with 5-HT1B receptors controlling serotonergic activity [O. Massot, J.C. Rousselle, M.P. Fillion, B. Grimaldi, I. Cloez-Tayarani, A. Fugelli, N. Prudhomme, L. Seguin, B. Rousseau, M. Plantefol, R. Hen, G. Fillion, 5-Hydroxytryptamine-moduline, a new endogenous cerebral peptide, controls the serotonergic activity via its specific interaction with 5-hydroxytryptamine1B/1D receptors, Mol. Pharmacol. 50 (1996) 752-762; J.C. Rousselle, O. Massot, M. Delepierre, E. Zifa, G. Fillion, Isolation and characterization of an endogenous peptide from rat brain interacting specifically with the serotonergic1B receptor subtypes, J. Biol. Chem. 271 (1996) 726-735; J.C. Rousselle, M. Plantefol, M.P. Fillion, O. Massot, P.J. Pauwels, G. Fillion, Specific interaction of 5-HT-moduline with human 5-HT1b as well as 5-HT1d receptors expressed in transfected cultured cells, Naunyn-Schmiedeberg's Arch. Pharmacol. 358 (1998) 279-286]. Cerebral tissue contents of 5-HT-moduline were determined in various rat brain areas after an acute restraint stress, and after repetition of this stress, to examine whether or not mechanisms involving this peptide could be affected by stress situations. The measurement of the peptide was carried out using specific polyclonal antibodies [B. Grimaldi, M.P. Fillion, A. Bonnin, J.C. Rousselle, O. Massot, G. Fillion, Immunocytochemical localization of neurons expressing 5-HT-moduline in the mouse brain, Neuropharmacology 36 (1997) 1079-1087] in a dot-ELISA (enzyme-linked-immunosorbent assay) assay in cortex, hippocampus, hypothalamus, substantia nigra, striatum and in adrenal glands. Tissue contents of 5-HT-moduline progressively and transiently increased in most studied brain regions and reached a maximal value 20 min after the beginning of the restraint stress. The increase in 5-HT-moduline tissue contents represented 323% of the value observed in unstressed control animals in the cortex, 207% in the hippocampus, 149% in the hypothalamus and 156% in the substantia nigra. Thereafter, the peptide content of the latter tissues diminished during the last 20 min of restraint and returned to control values within 1 h after the end of the stress period. The striatum did not show any significant variation of 5-HT-moduline content during restraint stress. In adrenal glands, the 5-HT-moduline content rapidly decreased (60% of controls) after the beginning of the restraint stress, the effect of this stress being progressively less pronounced, still representing 80% of controls after 40 min. Repetition of the restraint stress daily for 3 weeks totally abolished the effect of the stress on variations of 5-HT-moduline tissue content in all the studied brain regions. These results show that an acute restraint stress induces a rapid and significant increase in the amount of 5-HT-moduline contained in various brain areas. This phenomenon is likely to be related to the stress-induced 5-HT1B receptor desensitization which was previously demonstrated.

Acute Disease↗

Intradermal DNA immunization by using jet-injectors in mice and monkeys.

We have used spring powered jet injectors to deliver a solution of a naked DNA vaccine encoding the influenza hemagglutinin HA into the skin of mice and monkeys. We compared the immune responses induced by this needleless injection technique into the skin to the responses induced by a classical i.m. immunization. Both routes of immunization induced significant ELISA antibody titers and hemagglutination inhibition (HI) titers that were above the usual threshold values predictive of protection against influenza in mice and monkeys. In mice, both ways of immunization were equally efficient in inducing HA-specific CTL responses. Regarding antibody isotypes, the IgG1/IgG2a ratio was in favour of the IgG2a isotype for i.m. immunization and more balanced for i.d. immunization. The ability of the two injection techniques to induce immunity in mice did not correlate with transgene expression in the site of administration. In fact, local gene expression was 10-100 fold more important in the injected muscle as compared to the jet-injected skin when assessed by using the luciferase reporter system.

Animals↗

Hemorrhagic necrosis due to peliosis hepatis: imaging findings and pathological correlation.

Peliosis hepatis is an uncommon liver condition characterized by blood-filled cavities. We report the CT, angiographic and MR features of a case of peliosis hepatis with no obvious etiology and spontaneously regressing hemorrhagic necrosis. Helical CT showed multiple peripheral low-density regions with foci of spontaneous high density suggesting the presence of blood component. On MR imaging, the multiple peripheral lesions were hypointense on T1-weighted and hyperdense on T2-weighted images, with bright foci on all sequences suggesting subacute blood. Angiography showed no evidence of tumor or vascular malformation; multiple nodular vascular lesions filling in the parenchymal phase and persisting in the venous phase suggested blood-filled cavities. Pathological examination showed blood-filled spaces with no endothelial lining, characteristic of the parenchymal type of peliosis. Knowledge of the imaging features of hemorrhagic necrosis due to peliosis hepatis is important since it can be responsive to antibiotic therapy. Furthermore, differentiating hemorrhagic necrosis from hepatic abscess avoids dangerous and sometimes fatal percutaneous drainage.

Adult↗

Speculation on whether a vaccine against cryptosporidiosis is a reality or fantasy.

In this paper the authors question whether the development of a vaccine against cryptosporidiosis could be taken into consideration. The necessity and feasibility of such a vaccine for human and veterinary application is discussed. Developmental stages within the life cycle of the parasite that might act as possible targets for vaccine development are summarised, as well as the target antigens offered by molecular biology and immunology studies. Vaccination trials against cryptosporidiosis carried out so far, including the active and passive immunisation approach, are also overviewed. It seems that with respect to a Cryptosporidium vaccine two target groups can be considered: children of the developing world and neonatal ruminants. Antigens representing possible candidates for a subunit vaccine were identified based on their function, location and/or the immune response they evoke. While the active vaccination of newborn calves, lambs and goat kids has to face a number of important limitations, the passive immunisation approach, where dams were immunised to protect their progeny by colostral transfer, was proven to be a valuable alternative. Finally, a number of points of action for the near future are put forward.

Animals↗