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Biomedical subjects

P Millet

Publications and source records attributed to P Millet.

At least 73 records · Page 4Linked to original sources
PubMed1995

Quantification of benzodiazepine receptors in human brain using PET, [11C]flumazenil, and a single-experiment protocol.

A kinetic method using a multiinjection protocol, positron emission tomography (PET), and [11C]flumazenil as a specific ligand was used to study in vivo the flumazenil-benzodiazepine receptor interactions in the human brain. The model structure is composed of three compartments (plasma, free, and bound ligand) and five parameters (including the benzodiazepine receptor concentration). The arterial plasma concentration, after correction for metabolites, was used as the input function. The experimental protocol, which consisted of three injections of labeled and/or unlabeled ligand, allowed the evaluation of the five model parameters in various brain regions from a single experiment. In particular, the concentration of receptor sites available for binding (B'max) and the equilibrium dissociation constant (KDVR, VR being the volume of reaction) were estimated in five brain regions, including the pons, in which these parameters are identified for the first time (B'max = 4.7 +/- 1.7 pmol/ml and KDVR = 4.4 +/- 1.3 pmol/ml). Due to the large range of measured receptor concentrations, a linear correlation between B'max and KDVR was pointed out (r = 0.88, p < 0.0005) and was interpreted as a linear relationship between B'max and VR, the parameter KD being assumed constant. This result and its concordance with the published data are discussed. Simulation of the usual two-experiment Scatchard analysis, using the pons as a reference region, showed that the bias on the receptor concentration estimates introduced by this method is significant (from 20 to 40%) but can be corrected using an estimate of the receptor concentration in the pons. Furthermore, we propose a new experimental protocol, based on a Scatchard analysis of the PET data obtained with a partial-saturation experiment. This single-injection protocol is entirely noninvasive, and thus the estimation of the benzodiazepine receptor concentration and of the flumazenil affinity is now possible in human patients using a single 1-h experiment without blood sampling.

Adult↗
PubMed1995

Use of the rhesus monkey as an experimental model to test the degree of efficacy of an anti-sporozoite peptide malaria vaccine candidate combined with copolymer-based adjuvants.

Humoral response against sporozoites is not effective in protecting individuals from getting malaria. Reduction in the infectivity of sporozoites has not been quantified for most anti-sporozoite vaccines tested. Quantification requires animal models providing predictable prepatent periods, e.g., time elapsed between sporozoite inoculation and detection of parasitemia, to be used as an indicator of activity against sporozoites. A delay in prepatent period from vaccinated animals would therefore reflect a protective effect in reducing the number of parasites. We report the vaccination of rhesus monkeys with a synthetic peptide reproducing part of the repeated region of the circumsporozoite protein of Plasmodium cynomolgi. This peptide was conjugated to the carrier protein diphtheria toxoid and injected with four adjuvant formulations that differed only by the type of emulsion or immunomodulator. Because all five control animals had a synchronous prepatent period after challenge with live sporozoites, it was possible to quantify the protective efficacy for each vaccine formulation, even though all monkeys developed parasitemia. Sporozoite elimination correlated with the immunomodulator and the type of emulsion. Such elimination was related neither to antibody titer against the immunizing peptide or the whole sporozoite, nor to antibody isotype induced by the vaccine formulation.

Adjuvants, Immunologic↗
PubMed1995

Parameter and index images of benzodiazepine receptor concentration in the brain.

UNLABELLED: In vivo studies of ligand-receptor interactions with PET data are based on different approaches that provide either quantitative results (receptor density and affinity) or indices that are assumed to be correlated with the receptor concentration. The aims of this study are to obtain parametric images of benzodiazepine receptor concentration and of flumazenil affinity and to study the validity of two receptor concentration indexes. METHODS: A three-compartment ligand-receptor model, [11C]flumazenil, and experimental data obtained using a three-injection protocol in human volunteers were used to acquire parametric images. The delayed activity method and the apparent distribution volume (estimated using a two-compartment model) were also tested and their results compared with those of the multi-injection approach. RESULTS: Parametric images of receptor density, affinity and all kinetic parameters were obtained with acceptable variation coefficients. A correlation between receptor density and apparent affinity was found (r = 0.83; p < 0.0005). The correlation between receptor concentration and apparent distribution volume (estimated with three- and two-compartment models, respectively) was accessed using both a linear (the usual hypothesis) and a nonlinear correlation derived from the relationship between the receptor density and the affinity. CONCLUSION: In spite of the complexity of this protocol (three injections, a 2-hr experiment, blood sampling and a metabolite study), we showed that the multi-injection approach is suitable for parametric brain imaging. By using this approach as a reference, we deduced that the distribution volume and delayed activity images are valid methods in the usual range of the benzodiazepine receptor concentrations found in the human brain.

Brain↗
PubMed1995

[Conjugal mycosis fungoides].

INTRODUCTION: The pathophysiology of mycosis fungoides remains uncertain but HTLV I or a similar virus could be involved. We observed a couple who developed mycosis fungoides suggesting the infectious hypothesis might indeed be valid. CASE REPORT: A 70-year-old man who had often travelled in foreign countries developed parapsoriasis en plaques, lymphomatoid papulosis and mycosis fungoides successively over a thirty year period. Several years after the first manifestation of mycosis fungoides, his wife also developed a single plaque of mycosis fungoides. The diagnosis was confirmed on pathology slides and immunohistochemistry tests as well as on the basis of T-receptor gene rearrangement in both patients. Search for HTLV I was negative using serology tests and PCR on circulating lymphocytes. COMMENTS: The epidemiological situation in our observation (several trips in foreign countries and the delayed development of mycosis fungoides in the wife) favours the hypothesis of an infectious mechanism. Search for HTLV I was unsuccessful with classical virology methods. Certain recent work suggests a virus similar but different from the HTLV I virus could be involved in the pathogenesis of mycosis fungoides.

Aged↗
PubMed1994

A nonhuman primate model for human cerebral malaria: rhesus monkeys experimentally infected with Plasmodium fragile.

We studied the brains of rhesus monkeys infected with the primate malaria parasite Plasmodium fragile. Electron microscopy showed that, in these animals, erythrocytes infected with P. fragile undergo sequestration and that parasitized red blood cells adhere to endothelial cells in the cerebral microvessels by means of knobs. Cerebral microvessels with sequestered parasitized red blood cells were shown by immunohistochemical analysis to possess the platelet glycoprotein CD36, thrombospondin, and intracellular adhesion molecule-1. The formation of rosettes also was observed in the cerebral microvessels. In a fashion similar to human cerebral malaria, P. fragile produced neurological symptoms in the animals. Thus, rhesus monkeys infected with P. fragile, like those monkeys infected with Plasmodium coatneyi, can be used as a primate model to study human cerebral malaria.

Animals↗
PubMed1994

Plasmodium ovale: observations on the parasite development in Saimiri monkey hepatocytes in vivo and in vitro in contrast with its inability to induce parasitemia.

Exoerythrocytic stage parasites of the human malaria parasite Plasmodium ovale were cultured in vitro by inoculating primary cultures of hepatocytes from Saimiri sciureus boliviensis monkeys with sporozoites. Morphology and size of the liver stages were similar to previous in vivo descriptions in humans and chimpanzees. Saimiri monkeys did not develop parasitemia after repeated inoculations with P. ovale sporozoites. However, liver-stage parasites were observed in liver biopsies performed 7 days after sporozoite inoculation. Together with observations on other parasite development, these results demonstrate that host specificity for many malaria parasites occurs at the blood-stage level. Lack of host specificity of primary malaria parasite species for the liver forms the basis for the close relationship existing between human and nonhuman primate malaria species.

Animals↗
PubMed1994

Antibodies to ring-infected erythrocyte surface antigen (Pf155/RESA) protect against P. falciparum parasitemia in highly exposed multigravidas women in Malawi.

To determine whether antibodies to defined B-cell epitopes of Plasmodium falciparum antigens were related to protection against parasitemic attacks in highly exposed pregnant women, two samples of 235 with no initial P. falciparum parasitemia (NP) and 89 multigravidas who presented initial P. falciparum parasitemia (IP) were enrolled in an antimalarial prophylaxis trial in the Mangochi District in Malawi. Sera were collected under effective prophylaxis and tested for antibody measurement using FAST-ELISA. Mean antibody titers to synthetic peptides reproducing the 3 major B-cell epitopes of the ring-infected erythrocyte surface antigen (Pf155/RESA), as (EENV)4, (EENVEHDA)4 and (DDEHVEEPTVA)3, were higher in the NP than in the IP multigravidas, and this remained consistent within the season of malaria transmission (all p < 0.05). All antibodies to Pf155/RESA were positively intercorrelated within each group. Mean antibody titers to peptide (PNAN)5 reproducing the major B-cell epitope of the circumsporozoite protein (CS protein) were similar between NP and IP multigravidas in both dry and rainy season. Antibodies to Pf155/RESA epitopes may contribute to immune protection against blood-stage parasite multiplication in these highly malaria-exposed pregnant women.

Adult↗
PubMed1994

Effects of GABAA receptors activation on brain glucose metabolism in normal subjects and temporal lobe epilepsy (TLE) patients. A positron emission tomography (PET) study. Part I: Brain glucose metabolism is increased after GABAA receptors activation.

Though gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the human central nervous system, the metabolic response to GABA system activation remains imperfectly known. We studied in vivo with positron emission tomography (PET) the variations of glucose metabolism in the human brain after stimulation of the GABAA receptors by systemic administration of the specific GABAA agonist, 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP). These investigations were performed in three normal volunteers and as part of presurgical evaluation for temporal lobe epilepsy in six patients. While clinical and electroencephalographic (EEG) monitoring showed a sedative effect and sleepiness after THIP administration, glucose metabolism was paradoxically increased in grey matter structures, which are known to have a high density of GABAA receptors. These findings suggest that the pharmacological activation of GABA pathways, although inhibitory and producing a decrease of vigilance, increases the energetic demand at least during a phase of GABA agonist action, probably at the synaptic or at the glial cell level.

Adult↗
PubMed1994

Effects of GABAA receptors activation on brain glucose metabolism in normal subjects and temporal lobe epilepsy (TLE) patients. A positron emission tomography (PET) study. Part II: The focal hypometabolism is reactive to GABAA agonist administration in TLE.

Positron emission tomography (PET) using [18F]fluorodeoxyglucose (FDG) was used to study the metabolic response of focal hypometabolism to the administration of a specific GABAA agonist (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol), THIP, in six temporal lobe epilepsy (TLE) patients. After THIP injection, the increase of glucose metabolism in the hypometabolic focus was larger than the mean increase reported in the whole brain (Part I; Epilepsy Res., 19 (1994) 45-54). Within the hypometabolic focus, this increase was significantly higher in regions with the lowest basal metabolic level. This metabolic response in the hypometabolic focus, observed in the absence of any epileptic discharge during FDG accumulation and PET data acquisition, suggests that GABAA receptors are up-regulated or, at least, preserved in TLE.

Adult↗
PubMed1994

Immunologic characterization of Plasmodium vivax antigens using Plasmodium cynomolgi liver stage-primed immune sera.

We have shown in a previous study that immunization of a rhesus monkey (Macaca mulatta) with inactivated liver stages of the simian malaria parasite Plasmodium cynomolgi (B strain) produced high antibody titers against sporozoites, liver stages, and blood stages of P. cynomolgi. In the present study, we demonstrate that these anti-P. cynomolgi immune sera recognized P. vivax (Salvador I) antigens. In an indirect immunofluorescence assay, both postimmunization and postchallenge sera reacted with antigens of sporozoite, liver-, and blood-stage parasites. In Western blot analysis, postimmunization sera recognized four bands of 97, 93, 70, and 65 kD in sporozoite antigens; postchallenge sera further recognized three doublet (set of two) bands of 86-90, 73-78, and 44-52 kD. When blood-stage extracts were used as antigens, five bands of 118, 105, 76, 68, and 47 kD reacted with postimmunization sera; two doublet bands of 81-87 and 49-52 kD further reacted with postchallenge sera. None of these sera reacted with asexual blood-stage extracts of P. falciparum and P. malariae, or with a recombinant circumsporozoite protein of P. vivax.

Animals↗
PubMed1994

[Dermatological aspects of AIDS in western Africa. Apropos of 140 cases].

This clinical survey, carried out during a 3 years period in the Dermatological Department of Bouake Hospital (Ivory Coast) analyses the skin and mucous membranes troubles caused by AIDS among adults. It is the first of that kind in Western Africa. 140 patients were concerned, showing carious dermatological troubles, 25 of them were counted. Few tropical skin diseases have their clinical picture altered by immunodeficiency. However, the Buruli ulcer may be described, which has in this condition a particularly development. We have underlined the particularities of some ubiquitous diseases, either because they appear on black skin (seborrheic dermatitis, Kaposi's sarcoma, prurigo, woolly hair syndrome, ichtyosis) or because they were neglected, or because they take an extensive form (chronic herpes, profuse condyloma). At the end of the survey, we are proposing a classification of the dermatological troubles, according to their features which might suggest AIDS. On this account, erythroderma, scattered forms of Mycobacterium ulcerans infection, and noma, find a place among the troubles suggesting adult AIDS in sub-saharian Africa.

Acquired Immunodeficiency Syndrome↗
PubMed1994

[Imaging of parathyroid glands].

Ultrasonography (US) has become the gold standard of the preoperative detection of parathyroid masses. Provided that it is performed by sonographists aware of the normal and pathological anatomy of the neck, US can detect more than 80 per cent of the parathyroid masses. Ectopic masses, especially when they are intramediastinal, are rare but their diagnoses rely on more sophisticated procedures such as TI-Tc scintigraphy, CT, arteriography, MR, superselective venoius sampling. The specialized surgeons emphasize the lack of reliability of parathyroid US because of its operator-dependance. However, the accuracy of the technique enables some new treatments, percutaneous alcoolization and focal surgery under local anesthesia. One can regret that US is too often used as a diagnostic criterion of hyperparathyroidism, but this trend is explainable because of the difficulty to interpret monosymptomatic hypercalcaemia, especially in the elderly. The contribution of diagnostic imaging is undoubtfully worthwhile in persisting or recurrent hyperparathyroidisms, which are more often related with intracervical masses than with intramediastinal ones.

Angiography↗
PubMed1994

In vitro cultivation of exoerythrocytic stages of the simian malaria parasites Plasmodium fieldi and Plasmodium simiovale in rhesus monkey hepatocytes.

Exoerythrocytic stage parasites of Plasmodium fieldi and Plasmodium simiovale, 2 simian malaria parasites related to the human malaria parasite Plasmodium ovale, were cultured in vitro by inoculating primary cultures of hepatocytes from rhesus monkeys (Macaca mulatta) with sporozoites. Less than 1% of sporozoites developed into schizonts for either species. Structure and size of the liver stages in both species were similar to previous in vivo descriptions, and the time required for in vitro maturation correlated well with the prepatent periods described for each species. Such monkey models could be very useful in conducting scientific investigations on the pre-erythrocytic stages of P. ovale-like malaria parasites.

Animals↗
PubMed1993

An experimental vaccine cocktail for Plasmodium falciparum malaria.

Surface proteins from several different life-cycle stages of the malaria parasite Plasmodium falciparum were expressed at high levels in the yeast Saccharomyces cerevisiae. Purified proteins, both individually and in cocktails, were used to immunize mice and goats in conjunction with either Freund's adjuvant or a muramyl tripeptide-based adjuvant. Immune responses were measured by enzyme-linked immunosorbent assays and by the ability of antisera to inhibit (1) the invasion of hepatocytes by live sporozoites, (2) in vitro invasion of human erythrocytes by live merozoites, and (3) the development of oocytes in the mosquito vector. These results suggest that cocktails of different stage-specific antigens can provide the components necessary to block the development of the malaria parasite at multiple stages of its life cycle.

Animals↗
PubMed1993

Cytoadherence of Plasmodium falciparum-infected erythrocytes to microvascular endothelium is regulatable by cytokines and phorbol ester.

Cytoadherence to HB3 and FC27 strains of Plasmodium falciparum-parasitized red blood cells (PRBC) was studied under shear conditions to elucidate the pathways of adherence to microvascular endothelial cells (MEC). HB3 PRBC bound exclusively to MEC CD36 and intercellular adhesion molecule-1 (ICAM-1) receptors. FC27 PRBC bound to CD36 and another unidentified pathway but not to ICAM-1. Down-regulation of CD36 and ICAM-1 expression by phorbol 12,13-dibutyrate abolished HB3 PRBC adherence. Selective up-regulation of CD36 with interferon-gamma (IFN-gamma) increased PRBC adherence. Conversely, selective up-regulation of ICAM-1 with tumor necrosis factor did not elevate cytoadherence. These data have defined the relative contributions of both CD36 and ICAM-1 to PRBC binding to MEC and have provided evidence for the presence of a novel adhesion mechanism. Furthermore, in addition to antibody blocking of cell adhesion molecules, anti-IFN-gamma antibody therapy or pharmacologic manipulation of endothelial cell receptor expression may reduce PRBC sequestration and ameliorate the events associated with human cerebral malaria.

Antigens, CD↗
PubMed1993

Immunogenicity of the Plasmodium falciparum asexual blood-stage synthetic peptide vaccine SPf66.

The immunogenicity of the cocktail vaccine SPf66 against Plasmodium falciparum was investigated in rabbits, monkeys, and human volunteers. This polymerized peptide vaccine incorporates a portion of each of the 35-kD, 55-kD, and 83-kD blood-stage proteins, linked by an amino acid sequence reproducing one repeat from the circumsporozoite protein of P. falciparum. Results from this study show that vaccination with this vaccine molecule elicited high titers of antibodies to SPf66 and its constituents, but these antibodies did not correlate with regular or sensitive indirect fluorescent antibody (IFA) titers to blood-stage malaria parasites. However, rabbits injected with individual peptides produced antibodies with low affinity to indefinite parasite structures by immunoelectron microscopy, and rabbits injected with SPf66 had high antibody titers against the peptide (NANP)40. Consequently, these anti-SPf66 serum samples recognized P. falciparum sporozoites in the IFA. Such reactivity was not observed in monkeys or human volunteers vaccinated with SPf66. In addition, SPf66 components were recognized by antibodies induced by natural infection in humans and by laboratory-monitored infections in Aotus monkeys. These results suggest that this vaccine candidate merits further developmental work to better define immune response elicited by the copolymer to the parasite.

Adolescent↗