Six monkeys of three different species (mangabey, macaque and baboon) were infected with human im... more Six monkeys of three different species (mangabey, macaque and baboon) were infected with human immunodeficiency type 2 (HIV-2) NIH-DZ using intraperitoneal or intravenous injections of cell-free HIV-2 or autologous HIV-2-infected cells with no prior immunostimulation. Viral expression was demonstrated by reverse transcriptase activity in cells after coculture with human peripheral blood lymphocytes or by electron microscopy. Serum was analyzed by western blot, enzyme-linked immunosorbent assay (detection of antigen and antibody), and neutralization assay carried out using immunofluorescence techniques. The 6 inoculated animals seroconverted during the 1st month after inoculation and remained persistently infected after 6-11 months. We also observed proviral DNA by genomic analysis in the six tested samples. No sign of immunodeficiency disease has been observed so far. The data suggest that HIV-2 infection of nonhuman primates provides an acceptable animal model to investigate vaccination or specific immunotherapeutic procedures.
Background The preservation of autonomy and the ability of elderly to carry out the basic activit... more Background The preservation of autonomy and the ability of elderly to carry out the basic activities of daily living, beyond the therapeutic care of any pathologies, appears as one of the main objectives of care during hospitalization. Objectives To identify early clinical markers associated with the loss of independence in elderly people in short stay hospitals. Methods Among the 1,306 subjects making up the prospective and multicenter SAFEs cohort study (Sujet Agé Fragile: Évolution et suivi—Frail elderly subjects, evaluation and follow-up), 619 medical inpatients, not disabled at baseline and hospitalized through an emergency department were considered. Data used in a multinomial logistic regression were obtained through a comprehensive geriatric assessment (CGA) conducted in the first week of hospitalization. Dependency levels were assessed at baseline, at inclusion and at 30 days using Katz’s ADL index. Baseline was defined as the dependence level before occurrence of the event motivating hospitalization. To limit the influence of rehabilitation on the level of dependence, only stays shorter than 30 days were considered. Results About 514 patients were eligible, 15 died and 90 were still hospitalized at end point (n = 619). Two-thirds of subjects were women, with a mean age of 83. At day 30 162 patients (31%) were not disabled; 61 (12%) were moderately disabled and 291 severely disabled (57%). No socio-demographic variables seemed to influence the day 30 dependence level. Lack of autonomy (odds ratio (OR) = 1.9, 95% confidence interval (CI) = 1.2–3.6), walking difficulties (OR = 2.7, 95% CI = 1.3–5.6), fall risk (OR = 2.1, 95% CI = 1.3–6.8) and malnutrition risk (OR = 2.2, 95% CI = 1.5–7.6) were found in multifactorial analysis to be clinical markers for loss of independence. Conclusions Beyond considerations on the designing of preventive policies targeting the populations at risk that have been identified here, the identification of functional factors (lack of autonomy, walking difficulties, risk of falling) suggests above all that consideration needs to be given to the organization per se of the French geriatric hospital care system, and in particular to the relevance of maintaining sector-type segregation between wards for care of acute care and those involved in rehabilitation
The nickel(II) complexes of N,N′-xylylenebis(tetraazamacrocycles) have been isolated. The descrip... more The nickel(II) complexes of N,N′-xylylenebis(tetraazamacrocycles) have been isolated. The description of these dinuclear bismacrocyclic complexes have been carried out by means of magnetic measurements and spectrophotometric experiments (UV–Vis). The metal environment and the ligand shape have been specified by XANES and EXAFS experiments, since attempts to obtain suitable crystals failed.
ESR spectra show the simultaneous presence of a planar trans and a nearly planar cis isomers in t... more ESR spectra show the simultaneous presence of a planar trans and a nearly planar cis isomers in the 1:2 ratio for all S,O compounds Cu (R1R2N-CS-N-COR) 2 whereas an only isomer is present with the analogous S,N compounds. A strong tetrahedral distortion is observed when a bulky substituent is present on the nitrogen donor atom.
Hemoglobinopathies are the most frequent genetic diseases in the world. Among them, the Hb S vari... more Hemoglobinopathies are the most frequent genetic diseases in the world. Among them, the Hb S variant [beta6(A3)Glu-->Val], which, in the homozygous state, produces a severe disease known as sickle cell anemia with polymerization of Hb S inside red blood cells under hypoxic conditions. Additional mutations, in cis or in trans of the beta(S)-globin chain, may inhibit or enhance the polymerization process. We describe here a new hemoglobin (Hb) variant (Hb S-Clichy) which carries the beta(S)-globin chain and an additional mutation beta8(A5)Lys-->Thr. The variant was detected by routine electrophoretic techniques and cation exchange liquid chromatography (CE-LC). Globin chain separation by reversed phase LC (RP-LC) showed normal and abnormal beta chains, confirming that the additional abnormality was located in cis to Hb S. Electrospray ionization mass spectrometry (ESI-MS) gave a 57 Da mass decrease for the abnormal globin chain. The abnormal chain was isolated and submitted to trypsin digestion. Normal peptides betaT-1 and betaT-2 were not observed on the matrix-assisted laser desorption-time of flight (MALDI-TOF) mass spectrum but a new peptide betaT-1,2 was detected. Nano LC-ESI-MS/MS of the new peptide showed that the glutamic acid at codon 6 was replaced by a valine residue, and the lysine at codon 8 was replaced by a threonine residue, as confirmed by DNA sequencing. This example demonstrates that in a population where Hb S is present, every unidentified Hb needs to be clearly characterized to prevent major sickle cell syndromes. In addition, the identification of these variants must be considered in newborn screening for sickle cell disease, using either classical biochemical methods or MS techniques.
The aim of this study was to link the responses at different levels of biological organisation of... more The aim of this study was to link the responses at different levels of biological organisation of the endobenthic bivalve Scrobicularia plana differentially exposed to anthropogenic pressure. Clams were collected in April 2008 from three estuaries along a pollution gradient (Goyen<Loire<Seine). Biomarkers of defence (metallothionein concentration and glutathione-S-transferase activity) were activated in the Loire and the Seine. Biomarkers of damage revealed neurotoxicity (decreased AChE activity) and impairment of digestive enzyme activities (cellulase or amylase) in these estuaries. The highest lactate dehydrogenase activity was registered in the Loire estuary, in parallel with enhanced levels of vanadium (a metal present in petroleum), likely as a consequence of a small oil spill that occurred one month before the sampling collection. Physiological biomarkers (energy reserves as glycogen, lipids and proteins, condition and gonado-somatic indices) showed a few intersite differences. However, the median size was significantly lower in clams exposed to direct (chemicals) or indirect (available food) effects in the most contaminated site. Burrowing behaviour was disturbed in clams from both of the Loire and Seine estuaries, a response probably due to physiological impairment rather than to avoidance of contaminated sediment. The activation of defence mechanisms towards metals (metallothionein) and other classes of contaminants (the biotransformation enzyme glutathione-S-transferase) do not ensure a total protection since a number of impairments were observed at the infra-organismal (AChE and digestive enzyme activities) and individual (burrowing behaviour) levels in relation to the degree of anthropogenic pressure. However, even in the most contaminated estuary (Seine), historical records do not show a consistent decrease of S. plana populations.
Six monkeys of three different species (mangabey, macaque and baboon) were infected with human im... more Six monkeys of three different species (mangabey, macaque and baboon) were infected with human immunodeficiency type 2 (HIV-2) NIH-DZ using intraperitoneal or intravenous injections of cell-free HIV-2 or autologous HIV-2-infected cells with no prior immunostimulation. Viral expression was demonstrated by reverse transcriptase activity in cells after coculture with human peripheral blood lymphocytes or by electron microscopy. Serum was analyzed by western blot, enzyme-linked immunosorbent assay (detection of antigen and antibody), and neutralization assay carried out using immunofluorescence techniques. The 6 inoculated animals seroconverted during the 1st month after inoculation and remained persistently infected after 6-11 months. We also observed proviral DNA by genomic analysis in the six tested samples. No sign of immunodeficiency disease has been observed so far. The data suggest that HIV-2 infection of nonhuman primates provides an acceptable animal model to investigate vaccination or specific immunotherapeutic procedures.
Background The preservation of autonomy and the ability of elderly to carry out the basic activit... more Background The preservation of autonomy and the ability of elderly to carry out the basic activities of daily living, beyond the therapeutic care of any pathologies, appears as one of the main objectives of care during hospitalization. Objectives To identify early clinical markers associated with the loss of independence in elderly people in short stay hospitals. Methods Among the 1,306 subjects making up the prospective and multicenter SAFEs cohort study (Sujet Agé Fragile: Évolution et suivi—Frail elderly subjects, evaluation and follow-up), 619 medical inpatients, not disabled at baseline and hospitalized through an emergency department were considered. Data used in a multinomial logistic regression were obtained through a comprehensive geriatric assessment (CGA) conducted in the first week of hospitalization. Dependency levels were assessed at baseline, at inclusion and at 30 days using Katz’s ADL index. Baseline was defined as the dependence level before occurrence of the event motivating hospitalization. To limit the influence of rehabilitation on the level of dependence, only stays shorter than 30 days were considered. Results About 514 patients were eligible, 15 died and 90 were still hospitalized at end point (n = 619). Two-thirds of subjects were women, with a mean age of 83. At day 30 162 patients (31%) were not disabled; 61 (12%) were moderately disabled and 291 severely disabled (57%). No socio-demographic variables seemed to influence the day 30 dependence level. Lack of autonomy (odds ratio (OR) = 1.9, 95% confidence interval (CI) = 1.2–3.6), walking difficulties (OR = 2.7, 95% CI = 1.3–5.6), fall risk (OR = 2.1, 95% CI = 1.3–6.8) and malnutrition risk (OR = 2.2, 95% CI = 1.5–7.6) were found in multifactorial analysis to be clinical markers for loss of independence. Conclusions Beyond considerations on the designing of preventive policies targeting the populations at risk that have been identified here, the identification of functional factors (lack of autonomy, walking difficulties, risk of falling) suggests above all that consideration needs to be given to the organization per se of the French geriatric hospital care system, and in particular to the relevance of maintaining sector-type segregation between wards for care of acute care and those involved in rehabilitation
The nickel(II) complexes of N,N′-xylylenebis(tetraazamacrocycles) have been isolated. The descrip... more The nickel(II) complexes of N,N′-xylylenebis(tetraazamacrocycles) have been isolated. The description of these dinuclear bismacrocyclic complexes have been carried out by means of magnetic measurements and spectrophotometric experiments (UV–Vis). The metal environment and the ligand shape have been specified by XANES and EXAFS experiments, since attempts to obtain suitable crystals failed.
ESR spectra show the simultaneous presence of a planar trans and a nearly planar cis isomers in t... more ESR spectra show the simultaneous presence of a planar trans and a nearly planar cis isomers in the 1:2 ratio for all S,O compounds Cu (R1R2N-CS-N-COR) 2 whereas an only isomer is present with the analogous S,N compounds. A strong tetrahedral distortion is observed when a bulky substituent is present on the nitrogen donor atom.
Hemoglobinopathies are the most frequent genetic diseases in the world. Among them, the Hb S vari... more Hemoglobinopathies are the most frequent genetic diseases in the world. Among them, the Hb S variant [beta6(A3)Glu--&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;Val], which, in the homozygous state, produces a severe disease known as sickle cell anemia with polymerization of Hb S inside red blood cells under hypoxic conditions. Additional mutations, in cis or in trans of the beta(S)-globin chain, may inhibit or enhance the polymerization process. We describe here a new hemoglobin (Hb) variant (Hb S-Clichy) which carries the beta(S)-globin chain and an additional mutation beta8(A5)Lys--&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;Thr. The variant was detected by routine electrophoretic techniques and cation exchange liquid chromatography (CE-LC). Globin chain separation by reversed phase LC (RP-LC) showed normal and abnormal beta chains, confirming that the additional abnormality was located in cis to Hb S. Electrospray ionization mass spectrometry (ESI-MS) gave a 57 Da mass decrease for the abnormal globin chain. The abnormal chain was isolated and submitted to trypsin digestion. Normal peptides betaT-1 and betaT-2 were not observed on the matrix-assisted laser desorption-time of flight (MALDI-TOF) mass spectrum but a new peptide betaT-1,2 was detected. Nano LC-ESI-MS/MS of the new peptide showed that the glutamic acid at codon 6 was replaced by a valine residue, and the lysine at codon 8 was replaced by a threonine residue, as confirmed by DNA sequencing. This example demonstrates that in a population where Hb S is present, every unidentified Hb needs to be clearly characterized to prevent major sickle cell syndromes. In addition, the identification of these variants must be considered in newborn screening for sickle cell disease, using either classical biochemical methods or MS techniques.
The aim of this study was to link the responses at different levels of biological organisation of... more The aim of this study was to link the responses at different levels of biological organisation of the endobenthic bivalve Scrobicularia plana differentially exposed to anthropogenic pressure. Clams were collected in April 2008 from three estuaries along a pollution gradient (Goyen<Loire<Seine). Biomarkers of defence (metallothionein concentration and glutathione-S-transferase activity) were activated in the Loire and the Seine. Biomarkers of damage revealed neurotoxicity (decreased AChE activity) and impairment of digestive enzyme activities (cellulase or amylase) in these estuaries. The highest lactate dehydrogenase activity was registered in the Loire estuary, in parallel with enhanced levels of vanadium (a metal present in petroleum), likely as a consequence of a small oil spill that occurred one month before the sampling collection. Physiological biomarkers (energy reserves as glycogen, lipids and proteins, condition and gonado-somatic indices) showed a few intersite differences. However, the median size was significantly lower in clams exposed to direct (chemicals) or indirect (available food) effects in the most contaminated site. Burrowing behaviour was disturbed in clams from both of the Loire and Seine estuaries, a response probably due to physiological impairment rather than to avoidance of contaminated sediment. The activation of defence mechanisms towards metals (metallothionein) and other classes of contaminants (the biotransformation enzyme glutathione-S-transferase) do not ensure a total protection since a number of impairments were observed at the infra-organismal (AChE and digestive enzyme activities) and individual (burrowing behaviour) levels in relation to the degree of anthropogenic pressure. However, even in the most contaminated estuary (Seine), historical records do not show a consistent decrease of S. plana populations.
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Papers by Isabel Reims