Applicability of Macroscopic Wear and Friction Laws on the Atomic Length Scale.

Using molecular dynamics, we simulate the abrasion process of an atomically rough Fe surface with multiple hard abrasive particles. By quantifying the nanoscopic wear depth in a time-resolved fashion, we show that Barwell's macroscopic wear law can be applied at the atomic scale. We find that in this multiasperity contact system, the Bowden-Tabor term, which describes the friction force as a function of the real nanoscopic contact area, can predict the kinetic friction even when wear is involved. From this the Derjaguin-Amontons-Coulomb friction law can be recovered, since we observe a linear dependence of the contact area on the applied load in accordance with Greenwood-Williamson contact mechanics.

Molecular dynamics simulations of mixed lubrication with smooth particle post-processing.

A post-processing method for molecular dynamics (MD) simulations of friction based on the smooth particle approach is proposed, allowing--among other features--the introduction and evaluation of a solid-solid contact area arising due to direct asperity interaction. In order to illustrate the feasibility of this scheme, a large number of MD calculations of lubricated nanotribological systems with various asperity geometries and carefully selected numbers of lubricant molecules were carried out and analysed. In this manner, it is shown that the friction force as a function of load agrees very well with a three-parameter friction law which, in addition to the adhesion- and the load-controlled terms, contains a load-independent offset.

Antigenic diversity amongst ten geographic isolates of Plasmodium falciparum defined by merozoite invasion inhibition assay.

The extent to which human antibodies involved in functional immunity react with antigenic determinants varying between different isolates or strains of human malaria parasite Plasmodium falciparum will influence the design of vaccine against malaria. In this study, in vitro inhibition of merozoite invasion in erythrocytes by an immune human serum was used to define the antigenic differences in 10 isolates of P. falciparum from three endemic areas, i.e. Africa, South America and Southeast Asia. The serum inhibited the invasion of merozoites of all the strains but the extent of inhibition varied from low to moderate to high degree indicating antigenic differences amongst isolates of P. falciparum. The antigenic differences could not be correlated to the geographic origin of the parasite isolate.

Kinetic study of antifungal activity of amphotericin B, 5-fluorocytosine and ketoconazole against clinical yeast isolates using liquid-phase turbidimetry.

The fungal growth of clinical yeast isolates and of VW32 clone of Candida albicans were measured in vitro using a liquid-phase turbidimetric system (Bioscreen from Labsystems, France) in defined conditions. Cultures were performed in Shadomy's liquid medium and the fungal growth automatically evaluated every 10 minutes for 24 hours using various concentrations of drugs. The system made it possible to test 200 culture samples in one experiment. Yeast sensitivity to drugs was also measured by using our routine semi-automatic turbidimetric system. We observed that kinetic patterns of activity of each antifungal agent were typical. The in vitro tests showed that of 927 clinical yeast isolates 99.2% were sensitive to amphotericin B, 94.4% to 5-fluorocytosine and 69.7% to ketoconazole.

Detection of specific antibodies to Toxoplasma gondii by a competitive enzyme immunoassay using a monoclonal antibody against the P30 antigen.

An inhibition EIA using a monoclonal antibody against the major P30 Toxoplasma gondii surface protein was designed for detection of specific antibodies in human sera. The assay was based on the inhibition of binding of peroxidase labelled monoclonal antibody to Toxoplasma gondii crude antigen coated plates by the corresponding antibodies present in human sera. This rapid and simple assay was compared to indirect immunofluorescence, direct agglutination and an immunosorbent agglutination assay using 435 human sera. The specificity and sensitivity were 100% and 97% respectively. This test was found to be as sensitive as the dye test.

Characterization of a 225 kilodalton rhoptry protein of Plasmodium falciparum.

A monoclonal antibody (24C6 4F12) raised against Plasmodium falciparum culture supernatant antigens gave a multiple dot picture on schizonts when assayed by immunofluorescence on P. falciparum erythrocytic stages. The corresponding antigen was localized in the peduncle of rhoptries by immunoelectronmicroscopy. On Western blots of P. falciparum schizonts, a major antigen of 225 kDa and a minor one of 240 kDa were recognized by this McAb. Pulse chase analysis of [35S]methionine biosynthetic labeling of P. falciparum culture demonstrated that the 240 kDa molecule was the precursor of the 225 kDa and that its processing occurred between 0 and 4 h after synthesis. Biosynthesis of the 240-225 kDa antigen occurred only during schizogony.

[Identification in Plasmodium falciparum of a protein specifically binding human fibronectins]. / Identification chez Plasmodium falciparum d'une protéine se liant spécifiquement à la fibronectine humaine.

A fibronectin binding protein (FnBp) was identified in 3H isoleucine labeled P. falciparum schizonts using affinity chromatography on human fibronectin (Fn) coupled to Sepharose 4B. After incubation of Nonidet-P 40 parasite lysate with Fn-Sepharose, elution was performed with SDS-PAGE buffer. Analysis of FnBp by SDS-PAGE demonstrated a major band which migrated with an apparent Mr of 70,000 under reducing conditions. This band was not found when human or rabbit IgG coupled Sepharose 4B were used instead of Fn as control.

[Histopathology of the liver and kidney during malaria: relation to malaria-induced dyslipoproteinemia]. / Histopathologie du foie et du rein au cours du paludisme: rapports avec la dyslipoprotéinémie palustre.

A kinetic study concerning histologic and cytologic alterations during Plasmodium chabaudi infection of Swiss mice has been carried out. In liver, a reversible focal and non ischemic necrosis and a vascular congestion were observed together with an accumulation of malarial pigment. The endoplasmic reticulum cisternae and Golgi saccules of hepatocytes were highly distended. Hepatocyte microvilli in biliary canaliculi and in Disse' spaces were markedly less developed and less numerous than in normal liver. Intracytoplasmic lipid globules were found in large amount in hepatocytes before the peak of parasitaemia. Their number and size gradually diminished thereafter. Hepatocytic mitochondria showed important unspecific modifications probably in relation, at last partly, to the tissue anoxia. Some hepatocytic changes (intracytoplasmic lipid globules, enlargement of endoplasmic reticulum cisternae and Golgi saccules) were consistent with an increased synthesis of lipoproteins (VLDL). The kidney showed only minor histological and ultrastructural changes. However haemosiderin was observed in proximal tubules and in their bordering cells. The deposit of immune complex reported previously do not appear associated with tissular or cellular important alterations.

Enzyme immunoassay for detection of antigen in acute Plasmodium falciparum malaria.

A monoclonal antibody specific for an epitope of a 50 kDa Plasmodium falciparum antigen was used in an enzyme immunoassay for detection of the corresponding exo-antigen in culture supernatant and in the sera of 31 patients suffering from acute malaria. The assay was specific for Plasmodium falciparum and did not appear to be strain restricted. A parasitaemia level below 0.001% could be detected.

Localization, biosynthesis, processing and isolation of a major 126 kDa antigen of the parasitophorous vacuole of Plasmodium falciparum.

Monoclonal antibodies prepared against a 50 kDa antigen found in Plasmodium falciparum culture supernatants identify a 126 kDa polypeptide which can be localized by immunofluorescence and immunoelectronmicroscopy at the periphery of the schizonts. This polypeptide is released from the infected erythrocytes by mild saponin lysis and is probably a component of the parasitophorous vacuole. Pulse chase kinetic analysis demonstrated its disappearance from the parasitized red blood cell from 6 to 10 h after being synthesized and the concomitant appearance of the 50 kDa molecule in the culture supernatant. Purification of metabolically labeled, schizont infected cells demonstrated that spontaneous release of merozoites is needed for the processing of the 126 to the 50 kDa whereas reinvasion is not. Polyclonal antibodies were raised in rabbit against affinity purified 126 kDa protein. These antibodies, together with another 126 kDa specific monoclonal antibody have enabled us to characterize two other cleavage products of the 126 kDa antigen in culture supernatants, namely 47 and 18 kDa polypeptides. We believe that the processing of the 126 kDa protein into low molecular weight fragments reflects a proteolytic event which may participate in merozoite release.

Serotypic antigens of Plasmodium falciparum recognized by serotype-restricted inhibitory human sera.

Immune sera from some Cambodian refugees contain functional serotypic antibodies that inhibit invasion of erythrocytes by the Camp strain but not by the FCR-3 strain of Plasmodium falciparum. Using a new assay, the "competitive heterologous antigen assay" (CHAA), the serotypic antibodies in a pool of three inhibitory sera were characterized by the antigens they precipitated. In the CHAA, immunoprecipitation of antigens by antibodies to common or cross-reacting antigenic determinants was blocked with excess heterologous unlabeled FCR-3 antigens before 3H-labeled Camp schizont and merozoite antigens were immunoprecipitated. The predominant Camp strain serotypic antigens revealed after electrophoresis and autoradiography were the major 195 Kd glycoprotein surface antigen (gp195) and its processed products at 150, 83, 73, and possibly 45 Kd. Additional serotypic antigens were identified at 180, 130, 65, 50, and 32 Kd. It is likely that one or more of these serotypic antigens is a target for the serotypic antibodies that inhibit invasion.

Immunochemical analysis of a major antigen of Plasmodium falciparum (P126) among ten geographic isolates.

Protein P126, a parasitophorous vacuole major antigen of Plasmodium falciparum and precursor of 3 major exoantigens (50, 47, and 18 Kd in strain FCR-3) has been studied in 10 culture-adapted isolates originating from various endemic areas. Two monoclonal antibodies (specific for 50 and 47 Kd exoantigens, respectively) were used to immunoprecipitate culture supernatants and parasitized erythrocytes in each case. It was observed that all the parasite isolates reacted with both monoclonal antibodies, indicating the ubiquity of the epitopes analyzed. Further, two of the exoantigens (the 50 and 18 Kd of FCR-3) were found to have a stable molecular mass in all the isolates tested, whereas, the other one (47 Kd in FCR-3) was found to have a variable molecular mass, from 47 to 50 Kd. The molecular mass of the precursor varied from 126 Kd to 128 Kd. No correlation was found between geographic origin and antigenic size.

[Current role of amphotericin B in the treatment of deep mycoses]. / Place actuelle de l'amphotéricine B dans le traitement des mycoses profondes.

Amphotericin B (Am. B), a polyene heptaene, is an antifungal antibiotic substance produced by Streptomyces nodosus, a telluric actinomycetal from Venezuela. Although it is a very toxic substance and its pharmacokinetic is not completely known, Am. B is yet the former antifungal substance utilised against number of pathogenic agents of systemic mycoses. Am. B binds irreversibly to sterols of fungal cytoplasmic membranes causing a leak of potassium and other impairments leading the fungal cell to death. Further, Am. B might to induce an enhancement of humoral and cellular immunity. After intravenous perfusion, 95 per cent of Am. B binds to plasma lipoproteins. Only a low proportion of the Am. B serum level is detected in the CSF. Distribution of Am. B to extravascular inflammatory fluids and secretions might be letter. Am. B might be eliminated essentially by biliary way. Am. B toxic effects are very frequent. Generalized reactions are observed to the earlier doses. Toxic visceral, above all, nephrotoxic manifestations, appearing later. Recent results, from experimental and human infections suggest that Am. B encapsulated in liposomal vesicles is more active, less toxic and more easily administered.

In vitro growth and chloroquine sensitivity of Plasmodium falciparum (FCR-3 strain) in red blood cells containing HbC.

Freshly drawn AA and CC red cells were more suitable for in vitro development of Plasmodium falciparum than red blood cells (RBC) stored for 13 days before use. Growth rate inhibition in CC red cell cultures reached 31% in freshly drawn red cells and 57% in aged red cells of the same donor. Ultrastructural studies of CC cells revealed very important irregular cavities sometimes occupied by a granular content. Parasites in CC cells were generally normal but occasionally showed signs of functional impairment. P. falciparum growing in CC red cells was less sensitive in vitro to chloroquine than in AA red cells. This phenomenon may be explained either by the type of the hemoglobin of the host cell or to abnormal haematological parameters of the HbC homozygote donor, particularly the high proportion of neocytes. As metabolism of reduced glutathione is higher in young RBC and as chloroquine lyses parasitized RBC by reducing the regeneration capacities of this compound, the increased rate of young RBC in the CC red cell population was probably related to the decreased chloroquine sensitivity of P. falciparum growing in these cells.

A monoclonal antibody to a cell wall component of Candida albicans.

A heterologous fusion between mouse myeloma cells and rat lymphocytes resulted in the isolation of a rat immunoglobulin M monoclonal antibody with both agglutinating and precipitating activity. Indirect immunofluorescence and direct agglutination tests showed that the corresponding antigen was present in the cell wall of the three Candida species considered to be the most pathogenic, C. albicans, C. tropicalis, and C. glabrata, and also in the cell wall of C. guilliermondii. The antigen appeared to be predominantly polysaccharide in nature. Precipitation by counterimmunoelectrophoresis suggested that the epitope is shared by at least two separate molecules with different electrophoretic mobilities. Presence of this epitope varied from strain to strain within a given species and may be related to the morphological stage in the cell cycle. Antigen was shown to be present in the cytoplasm, in the periplasmic space, and at the cell surface of C. albicans. Indirect immunofluorescence also suggested that antigen is excreted from the cell.

Diagnosis of systemic candidiasis: application of co-counterimmunoelectrophoresis.

The accuracy of co-counterimmunoelectrophoresis was compared with mycological and clinical data for different groups of inpatients. The specificity and sensitivity of this method ranged from 100 to 69%. The co-specific precipitin line was observed during systemic infections caused by most opportunistic Candida species. The variations in the line in successive serum samples provided a simple means of serological surveillance. The test also detected seroconversion. The gradual disappearance of the line reflected a favourable prognosis, whereas its abrupt disappearance indicated unfavourable prognosis and correlated with the appearance of detectable circulating antigens.