Molecular arrangement between multivalent glycocluster and Pseudomonas aeruginosa LecA (PA-IL) by atomic force microscopy: influence of the glycocluster concentration.

New therapeutics strategy against cystic fibrosis seeks to prevent the adhesion of the bacterium Pseudomonas aeruginosa (PA) on the epithelial cells in the lungs. One of the factors that induces the adhesion is the interaction between natural glycocluster present on the cells and lectins such as the PA lectin LecA (PA-IL) present on the bacterium. By introducing synthetic glycoclusters with a great affinity with the lectin PA-IL, the adhesion can be prevented. In this study, we characterized, by atomic force microscopy, the interaction between a tetra-galactosylated glycocluster and the PA-IL lectin for high concentration of lectins (2.5 µM).We showed that the strong lectin/lectin interaction is reduced even for low concentration of glycoclusters (1 for 20 000 lectins). We assumed that it is due to the tensioactive behavior of the glycoclusters. It was shown that the arrangement of the created complexes induced different structures evolving from one-dimensional elongated aggregates to two-dimensional compact islands when increasing the glycocluster concentration. This evolution can be interpreted as the predominance of the glycocluster/lectin interaction.

Energy dissipation effects on imaging of soft materials by dynamic atomic force microscopy: a DNA-chip study.

Using amplitude-mode AFM (AM-AFM), we have obtained valuable information during these recent years through the study of amplitude and phase shift dependence on tip-sample separation, leading to a comprehensive understanding of the interaction processes. Two imaging regimes, attractive and repulsive, have been identified and a relationship between phase and dissipative energy was established, providing information on observed material properties. Most of the previous studies have concerned model systems: either hard or soft materials. In this paper, we present the analysis of a mixed system of soft structures on a hard substrate. This is a DNA chip for biological applications consisting of oligonucleotides covalently linked by a layer of silane to a silicon substrate. A detailed study of amplitude-phase curves as a function of the tip-sample separation allowed us to define the best experimental conditions to obtain specific information: we got reliable conditions to minimize noise during topographic imaging and an understanding of the processes of energy dissipation involved in the DNA breaking for DNA arrays. By calculating the energy dissipated as a function of the amplitude of oscillation, we have demonstrated a transition from an energy dissipation process governed by localized viscoelastic interactions (due to the soft layer) to a process governed by extended irreversible deformations (due to the hard substrate).

[Ethical contradictions in lung transplantation]. / Contradictions éthiques en transplantation pulmonaire.

Medical and scientific rationality often overlooked the importance of the symbolic dimension of personal and collective relationship to our body which organ transplantation cannot ignore. Hence the difficulty of the campaigns, with a widening gulf between resuscitation maneuvers intended for the sole organ perfusion during the sampling in patients with heart stopped and fostering an attitude of a friendly support person. A well-doing medical discourse for the recipient cannot ignore a dialogue on the meaning of a "donation" of which counter-donation carries the same symbolic values.

Evidence for autotetraploidy associated with reproductive isolation in Saccharomyces cerevisiae: towards a new domesticated species.

Partial or whole-genome duplications have played a major role in the evolution of new species. We have investigated the variation of ploidy level in a panel of domesticated strains of Saccharomyces cerevisiae coming from different geographical origins. Segregation studies and crosses with tester strains of different ploidy levels showed that part of the strains were well-balanced autotetraploids displaying tetrasomic inheritance. The presence of up to four different alleles for various loci is consistent with a polyploidization mechanism relying on the fusion of two nonreduced meiospores coming from two S. cerevisiae strains. Autotetraploidy was also in accordance with karyotype and flow cytometry analyses. Interestingly, most bakery strains were tetraploids, suggesting a link between ploidy level and human use. The null or drastically reduced fertility of the hybrids between tetraploid and diploid strains indicated that domesticated S. cerevisiae strains are composed of two groups isolated by post-zygotic reproductive barriers.

[End of the word and relegation of bodies in medicine: university formation of physicians]. / La fin de la parole et la relégation du corps en médecine: ses conséquences sur la formation Universitaire des Médecins.

Medicine is based on a growing demand for science. Yet, the patient's speech is ill adapted to the current desire of rationality. Inaccuracy and errancy have become the features of clinical examination. Self censorship of the speech gradually appears. Presenting the body becomes useless, if not suspicious. Medical technology replaces perceived subjectivity. What medicine says prevails over what the body knows. In a strange paradox, the "echo" precedes the speech. The risk of having an autistic medicine is looming. University teaching must be aware of this. The obvious gap between the speech and the body not only evades the ethical issue but also paradoxically deprives the medicine from its scientific acumen.

[Blood transfusion and ethics: new questions]. / Ethique et transfusion: reposer les questions.

Chairman to the French Institutional Review Board, Professor Didier Sicard raises blood donation issues from an ethical standpoint. The contaminated blood scandal focused on the necessity of reducing transfusion risks and regarded blood safety as an ethical mandatory requirement, a debatable subject to deal with. The author proposes to reconsider the nature of unpaid blood donations while advising not to scorn the remunerated gift when such is the case. As for the use of blood, he questions the solutions based on a zero risk perspective, in particular an excessive auto-transfusional practice or a restrictive use of blood, lately regarded as essential. Starting from the blood donation concern this article leads us to think over both our society's fears and the precautionary principle abuses.

[Whipple disease, initially diagnosed as sarcoidosis]. / Maladie de Whipple diagnostiquée primitivement sarcoïdose.

INTRODUCTION: Whipple disease is a multisystem infectious disease caused by Tropheryma whipplei. We report a case in which an initial diagnosis of sarcoidosis was changed to Whipple disease endocarditis. CASE: Based on clinical, radiographic, endoscopic and histologic findings, this 61-year-old man was diagnosed with sarcoidosis. Initial response to corticotherapy was good, but the patient required 35 mg of prednisone daily. The subsequent onset of clinical and laboratory signs of inflammation cast doubt on the diagnosis. After cardiac ultrasound revealed a mass 1 cm in diameter on the mitral valve, apparently vegetation, we diagnosed culture-negative infective endocarditis and ruled out most possible causes. PCR of a duodenal biopsy sample showed Tropheryma whipplei, thus confirming the diagnosis of Whipple disease, despite normal histological findings. After 3 weeks of intravenous gentamicin and amoxicillin treatment, oral cotrimoxazole was substituted. Follow-up transesophageal ultrasound showed no mitral vegetation. The patient, still under cotrimoxazole, has been off prednisone for 13 months and is completely asymptomatic. CONCLUSION: This case is an illustration of the difficulty in distinguishing Whipple disease from sarcoidosis in practice and of the importance of that distinction.

[Prevalence and risk factors of hepatitis A infection in an HIV-infected French population]. / Prévalence et facteurs de risque de l'hépatite A au sein d'une population de patients infectés par le virus de l'immunodéficience humaine.

BACKGROUND: There are common risk factors between hepatitis A virus (HAV) and human immuno deficiency virus (HIV) infections. OBJECTIVES: We tried to evaluate if HIV-infected patients could be at risk for HAV. More over, HAV could worsen prognosis of HIV infection and HAV vaccination was then to be considered. Thus we assessed the prevalence and risk factors of HAV infection in an HIV-infected population. PATIENTS AND METHODS: Seroprevalence and risk factors for HAV were studied among 154 HIV-positive patients followed in a Parisian hospital (mean age: 42 years, male patients: 70.8%, female patients: 29.2%). They were screened for HAV antibodies and answered a questionnaire on risk factors for HAV and means of HIV contamination. RESULTS: The global prevalence was 72.7% [IC95%: 65.7-79.7]. We excluded patients who were born in highly endemic areas where seroprevalence reached 60% [IC95%: 51.2-70]. The HAV seroprevalence was almost 100% in migrants from highly endemic countries and for those born before 1946. The multivariate analysis showed that risk factors were the geographic origin [OR=20.88; IC95%: 2.40-181], age [OR = 2.33; IC95%: 1.24-4.39], and hemophilia [OR = 13.78; IC95%: 1.34-141]. CONCLUSION: Our results suggest that a screening test for HAV antibodies should be performed before vaccination, especially in HIV-infected patients born after 1946 or in non-endemic countries.

Association of peripheral multifocal choroiditis with sarcoidosis: a study of thirty-seven patients.

OBJECTIVE: To assess the clinical spectrum of peripheral multifocal choroiditis (PMC) and its association with sarcoidosis. METHODS: Thirty-seven patients examined between November 1997 and November 2001 who met all diagnostic criteria for PMC were included in this retrospective study. Patients were assessed for the following signs of sarcoidosis: typical changes on chest radiography or computed tomography; predominantly CD4 lymphocytosis in bronchoalveolar lavage fluid; elevated serum angiotensin-converting enzyme levels; elevated gallium uptake; and noncaseating granuloma on biopsy. RESULTS: Most of the patients were female (30 of 37; 81%) and white (30 of 37; 81%). Mean +/- SD age at onset was 57.5 +/- 18.7 years. Seven (19%) of the 37 patients had biopsy-proven sarcoidosis and 18 patients (49%) with presumed sarcoidosis met at least 2 of the above-mentioned criteria for sarcoidosis but had normal biopsy results. Twelve patients (32%) had an indeterminate diagnosis. Patients with presumed sarcoidosis did not differ from those with proven sarcoidosis as regards the above-mentioned criteria, except for noncaseating granuloma, implying that more than two-thirds of patients (predominantly whites) had underlying sarcoidosis. Most patients with positive gallium scintigraphy had increased mediastinal uptake, as described in sarcoidosis. Patients with underlying sarcoidosis had more severe visual impairment due to cystoid macular edema (CME). Weekly methotrexate (0.3 mg/kg) seemed to control CME. CONCLUSION: White patients with PMC should be considered to have sarcoidosis. The identification of sarcoidosis in patients with severe ocular disease can help with therapeutic choices.

Tuberculosis due to Mycobacterium bovis after alemtuzumab administration.

We describe a patient with relapsing B chronic lymphocytic leukemia who developed systemic bacille Calmette-Guérin infection (BCGitis) after administration of alemtuzumab (Campath-1H).

Semen alterations in HIV-1 infected men.

BACKGROUND: Couples in whom the man is infected by human immunodeficiency virus (HIV) increasingly request assisted reproductive technology (ART) to allow safe procreation. Semen quality is critical in such situations. METHODS: Semen characteristics were evaluated in 189 HIV-infected men requesting ART. At the time of semen analysis all men were healthy and 177 were receiving anti-retroviral therapy. Comparisons were made with HIV-seronegative men, partners of women requiring IVF because of tubal infertility, after matching for age and sexual abstinence delay. RESULTS: The most significant semen alterations found in the HIV-infected men were reduced percentages of rapidly progressive sperm [median (range), 10% (0-30%) compared with 15% (5-30%) in the controls, P < 0.001], and increased concentrations of non-spermatic cells [3 x 10(6)/ml (0.2-16 x 10(6)/ml) compared with 1.1 x 10(6)/ml (0.1-14 x 10(6)/ml) in the controls, P < 0.001]. HIV-infected men also showed lower ejaculate volumes [2.8 ml (0.6-9.3 ml) compared with 3.6 ml (1.1-11 ml), P < 0.05] and total sperm counts [262.5 x 10(6) (0-1003 x 10(6)) compared with 310.5 x 10(6) (48.3-1679 x 10(6)), P < 0.05]. CONCLUSIONS: Semen evaluation in a large population of HIV-infected men requesting ART evidenced several alterations. Some of these anomalies might be related to anti-retroviral treatments.

HIV type 1-specific IgG2 antibodies: markers of helper T cell type 1 response and prognostic marker of long-term nonprogression.

The helper T type 1 (Th1) function of CD4(+) T lymphocytes is presumed to be of key importance in host defense against HIV-1. As the production of different antibody isotypes is dependent on this helper T function, we investigated whether HIV-1-specific responses of a particular IgG isotype could be a reliable marker of long-term HIV-1 control. Assessment of the IgG subclass distribution in the plasma of HIV-1-infected patients enrolled in the French prospective Asymptomatic Long-Term (ALT) cohort showed that IgG2 directed against HIV-1 Env gp41 and Gag proteins was associated with low viral load, high CD4(+) lymphocyte count, and weak neutralizing activity. By contrast, levels of anti-Env and anti-Pol IgG1 as well as the magnitude of neutralizing activity were correlated with the viral load and thus merely reflect the level of HIV replication. Furthermore, IgG2 directed against Gag proteins was significantly associated with HIV-1 p24-specific Th1 cell production of interferon gamma and interleukin 2. In multivariate analysis, only two variables, anti-gp41 IgG2 and plasma HIV-1 RNA, were found to be independent prognostic factors of remaining long-term nonprogressive over time. By providing new insight into the nature of an HIV-specific antibody response associated with the control of virus replication, these findings have implications for the design of HIV vaccines.