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Biomedical subjects

François Boué

Publications and source records attributed to François Boué.

10 recordsLinked to original sources

Charge stoichiometry inside polyelectrolyte-protein complexes: a direct SANS measurement for the PSSNa-lysozyme system.

We study by small angle neutron scattering and UV titration how the ratio of negative to positive charges, [-]/[+](intro), acts on the structure of complexes formed by short negatively charged polyelectrolyte chains (PSS) and globular positively charged proteins (lysozyme). The range of [-]/[+](intro) lies between 0.65 and 3.33. In all ratios, dense primary complexes are formed with radii around 10 nm. The species composition and the water content of the primary complexes are precisely obtained by the systematic use of the contrast matching of (deuterated) polymer or protein in SANS, yielding the compactness and the inner charge ratio [-]/[+](inner). The primary complexes have (i) an inner charge ratio [-]/[+](inner) close to 1 whatever [-]/[+](intro), (ii) a high total volume fraction (0.25-0.4), (iii) a constant radius (75 A) for [-]/[+](intro) 1, and (iv) a shell of PSS chains when [-]/[+](intro) > 1. Moreover, UV titration shows that there are free proteins if [-]/[+](introduced) < 1 and free PSS chains if [-]/[+](intro) is largely superior to 1. Hence, we observe that the primary complexes reach a finite size, controlled by electrostatic repulsion, and then aggregate at a higher scale with a fractal dimension of 2.1 characteristic of reaction-limited colloidal aggregation.

Electrolytes↗

Phase II trial of CHOP plus rituximab in patients with HIV-associated non-Hodgkin's lymphoma.

PURPOSE: To evaluate the safety and efficacy of rituximab adjunction to the cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen in patients with newly diagnosed AIDS-related non-Hodgkin's lymphoma. PATIENTS AND METHODS: HIV-seropositive patients with high-grade lymphoma of B-cell origin were eligible if they had no more than one of the following characteristics: CD4 cell count less than 100/microL, prior AIDS, or performance status less than 2. This multicenter phase II trial evaluated the response rate and disease-free survival after six courses of rituximab plus CHOP. Results Sixty-one patients were enrolled. All the patients were assessable for safety and 52 were assessable for the tumor response after treatment completion. Characteristics of patients were median age, 41 years; median CD4 cells, 172/microL; histology, diffuse large B-cell lymphoma (n = 42), immunoblastic (n = 2), Burkitt lymphoma (n = 16), and plasmablastic (n = 1); 42 patients with stage III to IV; International Prognostic Index 0 to 1 (n=31), and 2 to 3 (n = 27). Grade 3 or 4 toxicity consisted of febrile neutropenia in nine patients, anemia in 16 patients, and thrombocytopenia in five patients. Complete remission (CR) or unconfirmed CR was achieved in 40 of the 52 assessable patients, partial remission was achieved in five patients, and seven patients experienced progression. Forty-three patients were alive after a median follow-up of 33 months. The estimated 2-year overall survival rate was 75% (95% CI, 64% to 86%). Eighteen patients died: 16 as a result of lymphoma, one as a result of infection, and one as a result of encephalitis. CONCLUSION: Rituximab adjunction to CHOP produced a CR rate of 77% and a 2-year survival rate of 75% in patients with AIDS-related non-Hodgkin's lymphoma, without increasing the risk of life-threatening infections.

Adult↗

What tunes the structural anisotropy of magnetic fluids under a magnetic field?

In the present study, the structure of monophasic ionic magnetic fluids under a static magnetic field is explored. In these aqueous electrostatically stabilized ferrofluids, we vary both the isotropic interparticle interactions and the anisotropic dipolar magnetic interaction by tuning the ionic strength and the size of the nanoparticles. Small angle neutron scattering measurements carried out on nanoparticles dispersed in light water exhibit miscellaneous 2D nuclear patterns under a magnetic field with various q-dependent anisotropies. In this nondeuterated solvent where the magnetic scattering is negligible, this anisotropy originates from an anisotropy of the structure of the dispersions. Both the low q region and the peak of the structure factor can be anisotropic. On the scale of the interparticle distance, the structure is better defined in the direction perpendicular to the field. In the thermodynamic limit (q-->0), the model previously described in ref 10 matches the data without any fitting parameters: the interparticle interaction is more repulsive in the direction parallel to the magnetic field. At low q, the amplitude of the anisotropy of the pattern is governed by the ratio of two interaction parameters: the reduced parameter of the anisotropic magnetic dipolar interaction, gamma/Phi, over the isotropic interaction parameter, , in zero field, which is proportional to the second virial coefficient.

Journal Article↗

Polyelectrolyte-protein complexes: structure and conformation of each specie revealed by SANS.

We report here the structure of complexes made of proteins (lysozyme, positively charged) and polyelectrolytes (PSSNa, negatively charged). We stay in conditions where the volume fractions of the components are of the same order and where PSS concentrations correspond to a semidilute regime. The final complexes structure is determined by SANS. We obtain three main types of structures: (i) For a protein excess and for long polyelectrolyte chains, the network preformed by PSS chains still exists but chains are partially shrunk due to cross-linking by lysozyme. Macroscopically, samples are gelled. (ii) For a protein excess and for short polyelectrolyte chains, PSS chains are locally shrunk and do not form a network anymore. Lysozyme and PSS chains are embedded in dense 3-D aggregates that arrange in a fractal network at a larger scale. Macroscopically, samples are liquid. (iii) For a polyelectrolyte excess and whatever the chain length, the internal structure of the lysozyme changes. After an initial strong electrostatic binding, lysozyme is progressively unfolded thanks to a hydrophobic contact with PSS. The two chainlike objects are finally organized in a homogeneous costructure. Macroscopically, samples are liquids.

Electrolytes↗

In situ investigations on organic foam films using neutron and synchrotron radiation.

We report on small-angle neutron scattering (SANS) and X-ray scattering (SAXS) investigations of foam films stabilized by sodium dodecyl sulfate. Previous measurements on dry foams (Axelos, M. A. V.; Boue, B. Langmuir 2003, 19, 6598) have shown the presence of spikes in the two-dimensional scattering data which suggest that the incident beam is reflected on some film surfaces. The latter interpretation is confirmed by new neutron studies performed on ordered ("bamboo") foams which allow selection of single films. In the first case, we show that the spikes of the scattered intensity can be obtained by reflection on two parts of the foam, namely, the films and the Plateau borders. With synchrotron radiation, first observations of distinct interference fringes have allowed an accurate determination of the film thickness. A comparison with X-ray and neutron data is made, opening a general discussion about the capabilities of small-angle scattering techniques for studying the microscopic properties of foam films.

Journal Article↗

HIV+ MALT lymphoma remission induced by highly active antiretroviral therapy alone.

MALT lymphoma is usually described in association with Helicobacter pylori, HCV, HHV8, Campylobacter jejuni or in a setting of overreactive immunity. In HIV(+) patients, MALT lymphoma is most commonly described in children. We describe here an original case of HIV(+) MALT lymphoma with bronchial, conjuctival and laryngeal involvement for which a clinical and histopathological remission has been obtained with HAART alone. We conclude that HIV, as well as H. pylori, C. jejuni and HCV can target lymphogenesis in MALT lymphoma.

Antiretroviral Therapy, Highly Active↗

Structural and rheological properties of hydrophobically modified polysaccharide associative networks.

The phase behavior of hydrophobically modified chitosans (HMCs) in aqueous solution has been investigated using scattering and rheology experiments. We observed four regions on the phase diagram of the associative polymer: (i) a supernatant phase (unimers phase) at low polymer concentration; (ii) a dilute solution of intermolecularly bridged flowerlike micelles at intermediate concentration; (iii) an associative gel phase at high polymer content; and (iv) a phase separation. In the present paper, we discuss the structural and dynamical properties of the HMC associative networks (c > c*) at a fixed hydrophobic degree of substitution of 2% and fixed alkyl side chains (stickers) length C8 (domains iii and iv of the phase diagram). As the polymer concentration is increasing, a connecting network is formed from the percolation of bridges between micellar aggregates. In this regime, small-angle neutron scattering and light scattering measurements show that -50-nm flower aggregates are acting like junction points in the network. The effect of the concentration, the stress, and the shear on the structure of the network is discussed. In particular, we observe bridge-to-loop transitions and then the formation of microgels or a low-connected network under shear. Therefore, our results are compared to recent theoretical models and to the results reported for telechelic systems.

Hydrophobic and Hydrophilic Interactions↗

Triple nucleoside combination zidovudine/lamivudine/abacavir versus zidovudine/lamivudine/nelfinavir as first-line therapy in HIV-1-infected adults: a randomized trial.

OBJECTIVE: To compare the efficacy and safety of a triple nucleoside combination to a protease inhibitor-containing triple regimen as first-line antiretroviral therapy (ART) in HIV-1-infected patients. DESIGN: Open-label study in HIV-1-infected ART-naive adults, randomized to receive either Combivir (lamivudine 150 mg/zidovudine 300 mg twice daily) + abacavir (300 mg twice daily), or Combivir + nelfinavir (750 mg every 8 h) for 48 weeks. Plasma HIV-1 RNA, CD4 cell count and adverse events were assessed at baseline and weeks 4, 8, 16, 24, 32, 40 and 48. RESULTS: 195 subjects (131 men, 64 women), median age 34 years, were randomized: 98 received combivir/abacavir and 97 combivir/nelfinavir. Baseline median plasma HIV-1 RNA was 4.2 log10 copies/ml [Interquartile range (IQR): 3.7-4.5.2] and 4.1 log10 copies/ml (IQR: 3.8-4.6), respectively. Baseline median CD4 cell count was 387 cells/mm3 (IQR: 194-501) and 449 cells/mm3 (IQR: 334-605), respectively. Nine patients (3 vs 6, respectively) did not start treatment or did not have any available efficacy data. At week 48, using the intent to treat analysis (switch/missing equals failure), plasma HIV-1 RNA was <50 copies/ml in 54/95 (57%) and 53/91 (58%) of subjects, respectively. Median CD4 increase was +110 and +120 cells/mm3, respectively. Possible hypersensitivity reactions to abacavir were reported in four subjects (4%). CONCLUSION: The triple nucleoside combination combivir/abacavir is well tolerated as a first-line ART regimen in HIV-1-infected adults, with comparable antiviral activity to a nelfinavir-containing regimen at week 48.

Adolescent↗

[Kaposi's sarcoma].

Kaposi's sarcoma (SK) is a cutaneous disease mostly affecting elderly men of Mediterranean ancestry, people from sud-Saharan Africa and HIV infected patients. It is a proliferation of spindle cells. It's neoplastic origin remains controversial. Infection with a gamma herpes virus HHV8 is necessary for the development of KS. In organ recipient patients KS is observed and seems to be related to immune deficiency. In HIV infected patients an effect of HIV as a promoter on KS is added to immune deficiency. Half of HIV-HHV8 co-infected patients may develop KS. Therapeutic management of HIV infected KS patients is primarily to treat HIV infection. This treatment contributed to a dramatic decrease of KS incidence in developed countries. When antiretroviral treatment failed, conventional chemotherapy can be used. New therapies taking in count the complex mechanisms of the KS genesis are under evaluation.

Antineoplastic Combined Chemotherapy Protocols↗