[Variations of time perspective by social deprivation, what are the effects on smoking cessation?]. / Modification de la perspective temporelle par la précarité: quels effets sur le sevrage tabagique?

Smoking represents a major public health problem because of its high morbidity and mortality rates. Nearly half of the deaths in the lower class are caused by smoking. The socially deprived are physically and psychologically vulnerable. The instability of their situation increases the difficulty to invest in smoking cessation and certain time orientations linked to this social deprivation represent negative factors in the prognosis. Socially deprived populations do not understand the consequences of smoking unless they are in denial of the risks. The motivation to stop is essentially financial. The perception of smoking cessation is taken as a deprivation of pleasure. Independently of the social deprivation factors, taking into account the time perspective conveys necessary information of appropriate care.

Evidence for CTL-mediated selection of Tat and Rev mutants after the onset of the asymptomatic period during HIV type 1 infection.

The evolution of HIV-1 sequences over time is the result of the selection of mutant variants that have escaped from host immune responses or the outgrowth of mutants with increased viral replication, or both. We investigated the contribution of both selection processes to the overall evolution of the Tat and Rev regulatory gene sequences from four individuals, ranging in time from just prior to seroconversion to stable asymptomatic infection. After sequencing at least 15 clones per sample per gene, we analyzed the sequence evolution of the MHC-I motifs that were predicted from the MHC-I haplotypes of these patients. For each identified Tat sequence, we tested the activity of the corresponding encoded protein in a transactivation assay in vitro. Our results suggest that the evolution of the Tat and Rev sequences from these individuals can be explained by mutational escape of the MHC-I epitopes and that no mutations that replaced the original sequences in the viral population are associated with either an increase or decrease in Tat activity. CTL-mediated selection appears to be an important determinant of HIV-1 regulatory gene sequence evolution during the early stages of infection.

Blood monocytes infected in vivo by HIV-1 variants with a syncytium-inducing phenotype.

Extensive data have been obtained on sequence changes in the V3 region of the HIV-1 envelope protein that are associated with in vitro biological properties such as cell tropism and syncytium-inducing capacity. However, so far this concerned viruses isolated from peripheral blood mononuclear cells and thus did not discriminate between variants present in T lymphocytes or in monocytes. In this study, we analyzed viral sequences derived separately from uncultured T lymphocytes, blood monocytes, and plasma of an HIV-1-infected patient showing a neurological evolution of the disease. Sequences related to the V3 region and 18 amino acids downstream were obtained from 48 clones after PCR amplification. One predominant viral sequence close to the monocytotropic/non-syncytium-inducing (NSI) consensus sequence was observed in the three blood sources. Two viral species were specifically identified in monocytes (43% of the clones), showing clear differences from the consensus sequence and exhibiting the genetic determinants associated with the SI phenotype. Plasma-derived viruses with a similar V3 loop were obtained on in vitro isolation. Analysis of the biological properties of these selected viruses confirmed their monocytotropism and the syncytium-inducing phenotype as expected by the cell type in which the sequences were observed and the charge of the V3 loop. Structural analysis of these variants suggested an intermediate structure between NSI/monocytotropic and SI/lymphotropic V3 loops. Thus, in vivo circulating monocytes could be a reservoir for distinct HIV-1 variants with potential SI characteristics, at least in later stages of infection. Studying such variants over the course of the infection may shed light on their involvement in disease manifestations.

Molecular characterization of HIV viruses generated after in vivo ligation.

During the course of infection, human immunodeficiency virus type 1 (HIV-1) displays wide genotypic and phenotypic differences. Construction of chimeric viruses is useful to determine the genotypic basis that underlies phenotypic variations, but the procedure is time-consuming. Previously, it has been shown that co-transfection of truncated hemi-genomic HIV-1 proviral DNA can lead to generation of full-length infectious virus. In the study of HIV phenotypes, using this technique, it is important to determine whether recombination between the two hemigenomes occurs without mutations. After co-transfection, progeny recombinant viruses replicated at the same rate as the control. We purified progeny viruses from culture supernatants and determined mutations at the recombination site. It appeared that correct in vivo ligation depended on the purity of DNA and the restriction site used. It also appeared that some of the mutations observed affect replication, as progeny viruses bearing one of these mutations disappeared during in vitro cultures, whereas other mutants did not. Although this technique is widely applied to generate chimeric viruses, the results should be evaluated with care, since mutations influencing the phenotype of the progeny viruses may have been introduced.

Long-lasting rat growth enhancement by an immunoregulating synthetic peptide.

We have studied the long-lasting effects on rat weight gain of an active immunization with a peptide construction consisting of the covalent linkage of the 104-113 GH sequence to the 323-339 sequence of ovalbumin and to adjuvant muramyl dipeptide (MDP). The 104-113 GH sequence has already been identified as a potential epitope capable of enhancing growth hormome (GH) activity when complexed with the specific antibodies. Our results show that: a) 104-113 peptide antibodies after reacting with the endogenous GH produced a weight gain up to 7% higher than that observed in unimmunized rats; and b) the position of the adjuvant sequence in the molecule was critical for the immune response. Antibodies elicited in hypophysectomised rats had no effect on weight gain, thus confirming that the increase in hormonal activity is actually linked to the binding of specific peptide antibodies to endogenous GH.

Simulating lipophilicity of organic molecules with a back-propagation neural network.

From a training set of 7200 chemicals, a back-propagation neural network (BNN) model was developed for calculating the 1-octanol/water partition coefficient (log P) of molecules containing nitrogen, oxygen, halogen, phosphorus, and/or sulfur atoms. Chemicals were described by means of autocorrelation vectors encoding hydrophobicity, molar refractivity, H-bonding acceptor ability, and H-bonding donor ability. A 35/32/1 composite network composed of four configurations was selected as the final model (root-mean-square error (RMS) = 0.37, r = 0.97) because it provided the best simulation results (RMS = 0.39, r = 0.98) on an external testing set of 519 molecules. This final model compared favorably with a recently published BNN model using variables (atoms and bonds) derived from connection matrices.

Laser Doppler flowmetry: muscular microcirculation in anaesthetized horses.

Muscular microcirculation was studied in seven halothane anaesthetised horses in lateral recumbency using a laser Doppler flowmeter. A significant difference between the dependent and the uppermost triceps brachii was recorded. In the dependent muscles, microflow at first decreased and then increased up to the starting value. In the uppermost muscles, a significant rise of the microflow was measured.

Nonlinear neural mapping analysis of the adverse effects of drugs.

Numerous drugs have been identified as presenting adverse effects towards the driving of vehicles. A large set of these drugs was compiled and classified into ten categories. Nonlinear neural mapping (N2M) was used to derive a typology of these molecules and also to link their adverse effects to therapeutic categories and structural information.

[Depression in smoking pregnant women: impact on motivation to quit smoking]. / Dépression chez la femme enceinte fumeuse : impact sur la motivation à l'arrêt du tabac.

UNLABELLED: Despite the organization of smoking cessation program, the percentage of pregnant smokers remains too high in France. The knowledge of the factors limiting success of the attempt can help the smoking cessation. AIM: To evaluate the prevalence of depressive disorders in pregnant smokers compared to nonsmokers; assess their impact on motivation stopping smoking; verify their identification can be performed by midwives. MATERIALS AND METHODS: Prospective multicenter survey on 792 women (435 smokers and 357 non-smokers), the assessment of the current depression is made by the Hospital Anxiety Depression scale, and motivation to quit smoking by the Richmond test. RESULTS: Pregnant smokers compared to non-smokers, have more frequent depressive disorders (current: OR=2.4; history: OR=2). These problems do not decrease the motivation to quit, they are associated with a high nicotine dependence and low socioeconomic levels. Their testing can be done by midwives. CONCLUSION: Systematic screening for depression in pregnant women smoking could facilitate smoking cessation.

Optical properties and relaxation processes at femtosecond scale of bimetallic clusters.

The optical properties of Au-Ag and Ni-Ag clusters are measured by linear optical absorption spectroscopy and the time-resolved pump-probe femtosecond technique allowing a study of the influence of alloy or core-shell structure.

Coherent acoustic vibration of metal nanoshells.

Using time-resolved pump-probe spectroscopy, we have performed the first investigation of the vibrational modes of gold nanoshells. The fundamental isotropic mode launched by a femtosecond pump pulse manifests itself in a pronounced time-domain modulation of the differential transmission probed at the frequency of nanoshell surface plasmon resonance. The modulation amplitude is significantly stronger, and the period is longer than that in a gold nanoparticle of the same overall size, in agreement with theoretical calculations. This distinct acoustical signature of nanoshells provides a new and efficient method for identifying these versatile nanostructures and for studying their mechanical and structural properties.

Coreceptor usage of human immunodeficiency virus type 2 primary isolates and biological clones is broad and does not correlate with their syncytium-inducing capacities.

Entry of human immunodeficiency virus type 1 (HIV-1) into target cells is mediated by binding of the surface envelope glycoprotein to the CD4 molecule. Interaction of the resulting CD4-glycoprotein complex with alpha- or beta-chemokine receptors, depending on the biological phenotype of the virus, then initiates the fusion process. Here, we show that primary HIV-2 isolates and biological clones, in contrast to those of HIV-1, may use a broad range of coreceptors, including CCR-1, CCR-3, CCR-5, and CXCR-4. The syncytium-inducing capacity of these viruses did not correlate with the ability to infect via CXCR-4 or any other coreceptor. One cell-free passage of the intermediate isolates in mitogen-stimulated, CD8+ cell-depleted peripheral blood mononuclear cells resulted in the outgrowth of variants with CCR-5 only, whereas the coreceptor usage of late and early isolates did not change. Since HIV-2 is less pathogenic in vivo than HIV-1, these data suggest that HIV pathogenicity in vivo is not directly related to the spectrum of coreceptors used in in vitro systems.

Broadening of coreceptor usage by human immunodeficiency virus type 2 does not correlate with increased pathogenicity in an in vivo model.

The pathogenic properties of four primary human immunodeficiency virus type 2 (HIV-2) isolates and two primary HIV-2 biological clones were studied in an in vivo human-to-mouse chimeric model. The cell-associated viral load and the ability to reduce the severity of the induced graft-versus-host disease symptoms, the CD4/CD8 ratio and the level of repopulation of the mouse tissues by the graft, were determined. All HIV-2 strains, irrespective of their in vitro biological phenotype, replicated to high titres and significantly reduced graft-versus-host disease symptoms as well as the CD4/CD8 ratios. Reduction of graft repopulation caused by infection with the respective HIV-2 strains showed that the in vitro replication rate, syncytium-inducing capacity and ability to infect human macrophages did influence the in vivo pathogenic potential whereas broadening of coreceptor usage did not.

Antiviral resistance of biologic HIV-2 clones obtained from individuals on nucleoside reverse transcriptase inhibitor therapy.

OBJECTIVE: To study phenotypic and genotypic resistance of HIV-2 against nucleoside reverse transcriptase inhibitors (NRTI). METHODS: Biologic HIV-2 clones were generated from 3 patients before and after initiation of antiretroviral therapy with zidovudine (AZT) in patient RH2-7, AZT and didanosine (ddI) in patient PH2-1, and after addition of lamivudine (3TC) to AZT monotherapy in patient RH2-5. The sensitivity to NRTI of the virus clones, as defined by the 50% inhibitory concentration (IC(50)), was determined in vitro. The predicted amino acid sequences of the reverse transcriptase proteins from these clones were determined. RESULTS: Comparing the sensitivity of the biologic HIV-2 clones obtained after start of therapy with those from antiviral naive patients, resistance had developed to AZT (patients RH2-7 and RH2-5) and 3TC (patient PH2-1 and RH2-5). No resistance to AZT was observed in the biologic clone from PH2-1 obtained after start of therapy. The resistant clones from RH2-5 and PH2-1, but not RH2-7, contained amino acid mutations at positions where HIV-1 has been shown to mutate after AZT and 3TC treatment. CONCLUSIONS: Phenotypic resistance of HIV-2 to nucleoside analogues, which developed in HIV-2-infected patients treated with NRTIs, was associated with genotypic changes. Some of the mutations at amino acid positions in the HIV-2 reverse transcriptase gene corresponded with those involved in HIV-1 resistance, although no conventional mutations associated with resistance to AZT were observed.

Macrophage tropism of human immunodeficiency virus type 1 facilitates in vivo escape from cytotoxic T-lymphocyte pressure.

Early after seroconversion, macrophage-tropic human immunodeficiency virus type 1 (HIV-1) variants are predominantly found, even when a mixture of macrophage-tropic and non-macrophage-tropic variants was transmitted. For virus contracted by sexual transmission, this is presently explained by selection at the port of entry, where macrophages are infected and T cells are relatively rare. Here we explore an additional mechanism to explain the selection of macrophage-tropic variants in cases where the mucosa is bypassed during transmission, such as blood transfusion, needle-stick accidents, or intravenous drug abuse. With molecularly cloned primary isolates of HIV-1 in irradiated mice that had been reconstituted with a high dose of human peripheral blood mononuclear cells, we found that a macrophage-tropic HIV-1 clone escaped more efficiently from specific cytotoxic T-lymphocyte (CTL) pressure than its non-macrophage-tropic counterpart. We propose that CTLs favor the selective outgrowth of macrophage-tropic HIV-1 variants because infected macrophages are less susceptible to CTL activity than infected T cells.