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Biomedical subjects

C Goujon

Publications and source records attributed to C Goujon.

At least 19 recordsLinked to original sources

The skin allergenic properties of chemicals may depend on contaminants--evidence from studies on coumarin.

BACKGROUND/AIMS: Positive patch tests are considered representative of a contact allergy to the tested chemical. However, contaminants and derivatives rather than the suspected chemical itself could be responsible for the allergic skin reactions. Here, we tested the importance of contaminants in the sensitizing and allergenic properties of coumarin in mice and humans. Coumarin, an ingredient in cosmetics and fragrances, was chosen as the reference chemical since conflicting results have been obtained regarding its ability to induce contact allergy. In some chemical preparations, this could be explained by the presence of coumarin derivatives endowed with allergenic properties. METHODS: In mice, three different coumarin preparations were tested in the local lymph node assay. In humans, we assessed the irritant and allergenic properties of highly pure coumarin in nonallergic and fragrance-allergic patients. RESULTS: Pure coumarin did not exhibit irritant or sensitizing properties in the local lymph node assay. In contrast, two other commercially available coumarins and three contaminants that were detected in these coumarin preparations were identified as weak and moderate sensitizers, respectively. In humans, pure coumarin was extremely well tolerated since only 1 out of 512 patients exhibited a positive patch test to the chemical. CONCLUSIONS: These results indicate that coumarin cannot be considered as a common contact allergen and further emphasize that purity of chemicals is mandatory for the assessment of their allergenicity.

Adult↗

With a little help from a friend: increasing HIV transduction of monocyte-derived dendritic cells with virion-like particles of SIV(MAC).

Modification of dendritic cells (DCs) is a promising avenue for gene therapy purposes, given the versatility and the multiplicity of functions of these cells. In this study, we show that preincubation of monocyte-derived DCs with low amounts of non-infectious virion-like particles derived from the simian immunodeficiency virus (SIV(MAC) VLPs) increases up to 10-fold the efficiency of transduction by HIV-1 lentiviral vectors at low multiplicity of infections yielding up to 90% of transduced cells, in the absence of alterations of DCs behavior. This effect is restricted to DCs and specified by the viral accessory protein Vpx. Thus, preincubation with empty VLPs of SIV(MAC) can be used in transduction protocols to increase the efficacy of HIV-1-mediated modification of DCs.

Cell Line↗

Monodisperse dry granular flows on inclined planes: role of roughness.

Recent studies have pointed out the importance of the basal friction on the dynamics of granular flows. We present experimental results on the influence of the roughness of the inclined plane on the dynamics of a monodisperse dry granular flow. We found experimentally that there exists a maximum of the friction for a given relative roughness. This maximum is shown to be independent of the slope angle. This behavior is observed for four planes with different bump sizes (given by the size of the beads glued on the plane) from 200 microm to 2 mm. The relative roughness corresponding to the maximum of the friction can be predicted with a geometrical model of stability of one single bead on the plane. The main parameters are the size of the bumps and the size of the flowing beads. In order to obtain a higher precision, the model also takes into account the spacing between the bumps of the rough plane. Experimental results and model are in good agreement for all the planes we studied. Other parameters, like the sphericity of the beads, or irregularities in the thickness of the layer of glued particles, are shown to be of influence on the friction.

Journal Article↗

A human immunodeficiency virus Env inducible transcription system to examine consequences of gp120 expression.

According to several studies, the HIV-1 envelope gp120 protein and the co-receptor CXCR4 play an essential role in HIV-1 induced cell toxicity. Characterisation of the CD4-independent m7NDK isolate provided the opportunity of studying the effects of direct interactions between m7NDK gp120 and CXCR4. Therefore, an inducible expression system was designed enabling synthesis of HIV-1 Env proteins upon doxycycline induction. Analysis of the expression of the env gene of the m7NDK HIV-1 isolate revealed, unexpectedly, that even long-term expression of m7NDK gp120 did not result in cytotoxycity in CXCR4-positive or -negative cell lines. This is the first report of a CD4-independent HIV-1-protein inducible expression regulated through the Tet-On system and by an alternative splicing. Env inducible expression cell lines could constitute a useful cellular tool to undertake analysis of HIV Env protein expression.

Astrocytes↗

Quantification of human immunodeficiency virus type 1 proviral load by a TaqMan real-time PCR assay.

Proviral human immunodeficiency virus type 1 (HIV-1) DNA could be a useful marker for exploring viral reservoirs and monitoring antiretroviral treatment, particularly when HIV-1 RNA is undetectable in plasma. A new technique was developed to quantify proviral HIV-1 using a TaqMan real-time PCR assay. One copy of proviral HIV-1 DNA could be detected with 100% sensitivity for five copies and the assay had a range of 6 log(10). Reproducibility was evaluated in intra- and interassays using independent extractions of the 8E5 cell line harboring the HIV-1 proviral genome (coefficients of variation [CV], 13 and 27%, respectively) and peripheral blood mononuclear cells (PBMC) from a patient with a mean proviral load of 26 copies per 10(6) PBMC (CV, 46 and 56%, respectively). The median PBMC proviral load of 21 patients, measured in a cross-sectional study, was determined to be 215 copies per 10(6) PBMC (range, <10 to 8,381). In a longitudinal study, the proviral load of 15 out of 16 patients with primary infection fell significantly during 1 year of antiretroviral therapy (P = 0.004). In the remaining patient, proviral HIV-1 DNA was detectable but not quantifiable due to a point mutation at the 5' end of the TaqMan probe. No correlation was observed between proviral load and levels of CD4(+) cells or HIV-1 RNA in plasma. TaqMan PCR is sensitive and adaptable to a large series of samples. The full interest of monitoring proviral HIV-1 DNA can now be ascertained by its application to the routine monitoring of patients.

Anti-HIV Agents↗

Determination of essential amino acids involved in the CD4-independent tropism of the X4 human immunodeficiency virus type 1 m7NDK isolate: role of potential N glycosylations in the C2 and V3 regions of gp120.

Seven mutations in the C2, V3, and C3 regions of gp120 are implicated in the tropism of the first CD4-independent human immunodeficiency virus type 1 isolate, m7NDK. Site-directed mutagenesis revealed that three amino acids are essential to maintain this tropism, one in the C2 region and two in the V3 loop. Two mutations implied N glycosylation modifications.

Amino Acid Sequence↗

Selection of drug-resistant variants in the female genital tract of human immunodeficiency virus type 1-infected women receiving antiretroviral therapy.

We investigated human immunodeficiency virus (HIV) type 1 RNA, proviral DNA, and antiretroviral drug-resistant variants in cervicovaginal secretions of HIV-1-infected women receiving antiretroviral therapy. The prevalence of detectable HIV-1 RNA in genital secretions was inversely related to the number of antiretroviral drugs taken by the patients. Proviral DNA was detected in approximately half of all samples of cervicovaginal secretions from HIV-1-infected women, regardless of the presence or absence of HIV-1 RNA in cervicovaginal secretions and of the antiretroviral regimen. In cervicovaginal secretions of most women with persisting genital viral replication, HIV variants exhibiting mutations associated with drug resistance against protease and reverse-transcriptase pol genes were found. Our observations indicate that antiretroviral therapy is not effective in purging the female genital tract of cell-associated provirus and that antiretroviral drugs that penetrate the female genital tract at suboptimal concentrations exert a potent selective pressure on genital HIV variants when local replication of free HIV-1 RNA persists.

Adult↗

High levels of drug-resistant human immunodeficiency virus variants in patients exhibiting increasing CD4+ T cell counts despite virologic failure of protease inhibitor-containing antiretroviral combination therapy.

The genotypic mutations associated with indinavir resistance were analyzed in 27 patients who exhibited sustained CD4+ T cell responses to highly active antiretroviral therapy (HAART), despite virologic failure of treatment. After 12 months of HAART, 1 or 2 primary resistance mutations had occurred in 18 (66%) of the patients, and secondary mutations had accumulated in 22 (88%) of the patients. The number and patterns of mutations in the patients who exhibited discrepant responses to HAART did not differ from those observed in patients who exhibited immunologic and virologic failure to therapy. Results indicate that many patients have prolonged immunologic benefits, despite the development of virologic failure and protease inhibitor mutations. The clinical course of this group of patients calls into question the relevance of genotypic resistance and plasma human immunodeficiency virus RNA level as surrogate markers in patients receiving HAART.

Amino Acid Sequence↗

Differences in sexual risk behaviour between young men and women travelling abroad from the UK.

BACKGROUND: Identification of people who most frequently engage in sexual risk behaviour while travelling abroad would be useful for the design and targeting of health education and promotion campaigns. METHODS: Eligible participants were people living in the UK aged 18-34 years who had travelled abroad without a partner in the previous 2 years. Respondents were first screened for eligibility as part of representative face-to-face and telephone surveys by a market research company. Eligible individuals who agreed to take part then underwent a computer-assisted telephone interview. Reinterviewing continued until 400 eligible people had been contacted. We also interviewed a control group of 568 young people who had travelled abroad without a partner in the previous 2 years but who did not report a new sexual relationship during their travels. FINDINGS: One in ten of the eligible participants reported sexual intercourse with a new partner. Travellers who reported a new sexual relationship abroad were also likely to report large numbers of sexual partners at home. Of the 400 people who had a new sexual partner abroad, 300 (75%) used condoms on all occasions with the new partner. Logistic regression modelling showed differences between men and women in those factors linked to the practice of unsafe or safer sex while travelling. For men, patterns of condom use abroad with casual partners (p<.0001) reflected patterns of use at home (p<0.001), whereas for women, patterns of condom use varied according to their partners' backgrounds (p<.0001). INTERPRETATION: Condoms are widely used among young travellers, but patterns of use vary by sex. Campaigns about sexual health targeted at international travellers should continue, not least because young people who meet new sexual partners abroad may be a convenient proxy group for that minority of the population who report most sexual partners at home. Such campaigns should be designed differently for men and women.

Adolescent↗

Effect of UVB 311 nm irradiation on normal human skin.

Ultraviolet radiation B (UVB) on the skin induces erythema, inflammation and modifications of the immune system. These changes have been reported after excessive short-term or long-term exposure to broad spectrum UVB. In this study, we examined the effects of local repetitive UVB irradiation of 311 nm wavelength on the skin of seven young volunteers. Skin biopsies were taken before and after UVB irradiation, and we immunohistochemically analyzed the expression of CD1a and HLA-DR antigens of Langerhans cells (LC), the possible infiltration of dermis/epidermis by CD11b macrophages, the modifications or the induction of intercellular adhesion molecule-1 (ICAM-1), E-selectin and vascular cell adhesion molecule-1 (VCAM-1) involved in the binding of leukocytes to the endothelial surface and the development of perivascular infiltrates of LFA-1+ mononuclear cells. We also determined the expression of substance P receptors (SPR) using biotinylated substance P (SPB). Exposure of UVB 311 nm induced a drastic reduction of CD1a+ cells and a moderate increase of HLA-DR+ dendritic cells in the epidermis without infiltration by CD11b macrophages. An increase of the binding of SPB to upper layer epidermal cells was noted in five of seven biopsies. In the dermis, vessel-associated ICAM-1 expression increased and an induction of E-selectin occurred on nearly 20 to 40% of endothelial cells, but VCAM-1 expression remained undetectable. The percentage of LFA-1+ cells did not change significantly after irradiation. These observations may be compatible with a selective role of UVB 311 nm on the skin immune response.

Adult↗

[Which vaccination schedule, which vaccines? The constraints of time and age].

Several factors must be taken into account in planning vaccination schedules for overseas travelers. The first factor is to determine requirements mandated by applicable laws in the destination country and in France governing professional travel such as by military personnel. The other factors involve risk assessment including local health and epidemiological conditions, living conditions during the stay, and personal profile of the traveler (e.g. age and previous vaccination). Tropical areas are not the only destinations where infectious risks requiring vaccinations are found. Vaccination against diseases such as diphtheria and tick-borne encephalitis is necessary for several countries in Europe. Pre-travel planning provides a timely opportunity for updating basic vaccination requirements (e.g. tetanus and polio). For the growing number of elderly travelers, accurate evaluation of immune status may be difficult either because these subjects may never been vaccinated but only exposed to the wild germ during childhood or because their vaccinations may have been performed long ago. In both cases one cannot be sure of the quality of the anamnestic response to booster injections. A frequent limitation on vaccination planning for travelers is time available before departure.

Age Factors↗

[Real information needs of the traveller before his departure. Results of a survey by questionnaire].

This study is based upon 727 questionnaires completed by French travellers 10 days after intercontinental travel. The response rate was 40%. Two out of 5 travellers had generally mild health problems: fever (12%), diarrhoea (36%). Forty-six of them took drugs, which they had brought with them during their travel. Ten per cent had a satisfactory visit to a local physician. Medical informations given before departure appears to be sufficient, useful and relevant in more than 90% of cases. The traveller would like to receive them from his own physician or from vaccination centers. Other informations as insurance, assistance, administration, finances, appeared to have been incorrectly perceived by 20% of the travellers. The travel agent is the one who should provide adequate information. The traveller, in general, plans to do more travelling for his own well being if not for his work. Would not the bigger risk for him be "not to travel at all".

Adult↗

Infarction in the anterior rostral cerebellum (the territory of the lateral branch of the superior cerebellar artery).

We report 9 patients with an isolated infarct of the anterior part of the rostral cerebellum, ie, the territory of the lateral branch of the superior cerebellar artery. Clinicoanatomic correlations are based on CT, MRI, or both in 8 patients and on pathologic data in the ninth. The main clinical features were ipsilateral dysmetria and axial lateropulsion, dysarthria, and unsteadiness. In 1 patient, the clinical presentation mimicked a lacunar stroke (dysarthria and clumsy hand syndrome). There were no edematous cerebellar infarcts with signs of brainstem compression, and all patients spontaneously improved without significant sequellae. Angiography in 2 patients and pathologic examination of arteries in 1 patient disclosed no occlusion in the vertebrobasilar system. Six patients had a cardiac source of emboli. In conclusion, infarcts of the anterior part of the rostral cerebellum can be regarded as a benign condition in which there is, frequently, a cardiac source of emboli.

Adult↗

[Optimal length of antibiotic therapy in aspirated cerebral abscess].

Between 1983 and 1988, 22 patients with brain abscess were admitted to our neurosurgery department; 2 patients deeply comatose on admission and who died on the first day were excluded from this study. Treatment consisted of needle aspiration of the abscess and antibacterial therapy initially using a broad-spectrum antibiotic later replaced, in all cases, by an antibiotic found to be active in vitro against the organism(s) isolated. The portal of entry was eradicated as early as possible. The duration of antibiotic therapy was determined according to the changes observed on computerized tomography images classified as cavitary, nodular, hypodense or normal. Nodular images were taken as reflecting an inflammatory state in the healing process, and hypodense images as sequelae, so that antibiotics were withdrawn in patients with such images. Altogether, 62 per cent of the patients received antibiotics for 60 days and 95 per cent for 90 days. There was no recurrence. In some patients with deep or, chiefly, multiple abscesses, treatment was pursued. In any case, antibiotics should not be given for more than 90 days if the initial treatment has proved effective, since cure is achieved in 45 to 60 days on average.

Anti-Bacterial Agents↗

Prognosis of ruptured intracranial mycotic aneurysms: a review of 12 cases.

Intracranial mycotic aneurysms (IMA) occur in 1-3% of all infective endocarditis. Although spontaneous resolution was evidenced on serial angiograms in many asymptomatic cases, the prognosis, if they rupture, is reported to be worse and partly contingent on the therapeutic approach. Among 12 patients (six acute and six subacute endocarditis) with ruptured IMA, six were treated surgically and four were treated medically. Two patients died during rupture before any treatment could be started. Six patients had a sudden rupture manifested by coma, less clear consciousness seizures, hemiparesis unilateral mydriasis. CT-Scan showed intracerebral, intraventricular and subarachnoid haemorrhage. Ten angiograms showed 11 IMA. For patients with ruptured IMA, the decision for surgical treatment was made in the presence of deepening coma and extensive mass-lesion on CT-scan (one of six died in the postoperative period). Others received medical treatment (four cases: all survived) and were followed-up with serial angiographies. Of the nine patients who survived, five remained free of any disability 1-4 years later. We suggest that the prognosis of ruptured IMA (25% mortality rate) is not as bad as previously reported if surgery following angiography is performed early in the presence of deepening coma and extensive lesion.

Adolescent↗

[The role of surgery and low molecular weight heparin in the treatment of cerebral venous thrombosis. Apropos of 2 cases].

For one case of thrombosis of sinus sagittalis superior joint haemorrhagic cerebral softening necessitates surgical draining of haemorrhagic focus grown to a true intracranial haematoma; for the another case direct low molecular weight heparin treatment obtained a mere evolution. Authors are of the opinion that early low molecular weight heparin treatment is able to avoid massive haemorrhage.

Adult↗

Magnetic resonance imaging in the exploration of dissection of the internal carotid artery.

Five patients with recent spontaneous or post-traumatic dissection of the internal carotid artery (ICA) were explored by magnetic resonance imaging (MRI), using T1-weighted axial sections in all cases. In four patients examined during the subacute phase (after 7 days) the diagnosis of ICA dissection was strongly suspected on the association of a very high intensity signal produced by the parietal haematoma with a contiguous signal void area corresponding to the lumen of the ICA. A control MRI examination performed in two patients 2 months after the onset of dissection showed that it had regressed and that the carotid arteries were patent, which was confirmed by angiography. In the fifth patient MRI provided evidence for the evolution of a post-traumatic dissection towards thrombosis. The MRI image of carotid dissection at the subacute phase seems to be characteristic. MRI is also useful to follow up dissections under treatment and to postpone angiography. The latter, however, remains necessary to investigate for associated arterial dysplasia and to evaluate the sequelae of dissection.

Adult↗