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P Yeni

Publications and source records attributed to P Yeni.

At least 73 records · Page 4Linked to original sources

Incorporation of amphotericin B (AMB) into liposomes alters AMB-induced acute nephrotoxicity in rabbits.

To investigate the protective effect of liposomes on acute amphotericin B (AMB) renal toxicity, we compared in rabbits the acute toxicity of 4 mg/kg of free-AMB and 4 or 10 mg/kg of liposomal AMB (L-AMB) during 90 min after antibiotic infusion. Free-AMB exhibited immediate nephrotoxicity with a 44% decrease of the glomerular filtration rate and alteration of tubular cell membrane permeability expressed as increases in urinary pH (6.5 vs. 4.7), potassium fractional excretion (95% vs. 30%) and sodium fractional excretion (26% vs. 4%). Urinary excretion of the lysosomal enzyme N-acetylglucosaminidase was unchanged by free-AMB. Incorporation of AMB into liposomes prevented the toxic effects of free-AMB on glomerular filtration and tubular cells membrane, but significantly increased N-acetylglucosaminidase urinary excretion (380 and 180% in animals receiving 4 and 10 mg/kg of L-AMB, respectively). Absolute AMB urinary excretion during the experiment was unchanged by liposomes and was always less than 1% of the total dose administered. Liposomes alone exhibited no toxicity. These results suggest that liposomes could increase the interaction between AMB and lysosomes leading to an additional mechanism of cellular injury. They admonish close monitoring of renal function and enzymuria in clinical situations in which L-AMB is being used.

Amphotericin B↗

Genetic control of the humoral response to cryptococcal capsular polysaccharide in mice.

Cryptococcus neoformans is responsible for opportunistic infections in patients with cellular immune defects. However, C. neoformans-specific capsular polysaccharide antibodies have been shown to participate in host defenses during cryptococcosis. We investigated the humoral response after primary immunization in various inbred strains of mice and the genetic control. Our data strengthen the arguments for the T-independent type-2 nature of cryptococcal antigen, since CBA/N mice were unable to produce specific antibodies. They show that the influence of the genetic background is predominant for the good response with at least four independent autosomal genes governing this response, including an Igh control as reported for other polysaccharides. Immunization of intra-H-2 recombinant mice on a B10 background allowed us to identify a major histocompatibility complex control located in the subregion E alpha. The genetic control of antibody production following immunization with cryptococcal polysaccharide might explain the high variability of humoral responses during cryptococcosis.

Animals↗

Cryptococcus neoformans antibody levels in patients with AIDS.

Anti-Cryptococcus neoformans capsular polysaccharide (CPS) antibodies were measured by ELISA in patients with AIDS related complex or AIDS without a known history of cryptococcosis and in heterosexual healthy controls. Total and IgG anti-CPS antibody activity was rarely detected in patients, with mean levels lower than in controls, whereas IgM antibody activity was similar in the 3 groups. Since both humoral and cellular immunity appear to be of great importance during cryptococcosis, the inability of AIDS patients to synthetize specific IgG antibodies could impair an alternative host defence mechanism to cellular immunity.

AIDS-Related Complex↗

Lymphadenopathy-associated virus type 2 in AIDS and AIDS-related complex. Clinical and virological features in four patients.

Lymphadenopathy-associated virus type 2 (HIV 2) was isolated from 3 patients with AIDS and 1 with AIDS-related complex. Clinical features were similar to those in patients infected with HIV 1. Viral isolates were characterised by hybridisation with HIV 1 and HIV 2 DNA probes. HIV 1 and HIV 2 serological studies were performed by enzyme-linked immunosorbent assay (ELISA), western blot, and radioimmunoprecipitation assay. HIV 2 IgG antibodies were detected in all sera. The molecular weights of the most representative HIV 2 proteins were determined by immunoblot. Cross-reactivity was restricted to HIV 1 and HIV 2 core proteins. In all 4 patients the neurotropism of HIV 2 was demonstrated by virus isolation from the cerebrospinal fluid and/or by evidence of intrathecal HIV 2 IgG synthesis. All sera were antibody negative by HIV 1 ELISA. An assay specific for HIV 2 is needed for screening of blood donations and for diagnosis and seroepidemiological study of HIV 2 infection.

AIDS-Related Complex↗

Production, characterization, and antibody specificity of a mouse monoclonal antibody reactive with Cryptococcus neoformans capsular polysaccharide.

Two monoclonal immunoglobulin G1 antibodies reacting with Cryptococcus neoformans capsular polysaccharide (CNPS) were produced in mice by using a carefully defined procedure for immunization with unmodified CNPS purified from C. neoformans serotype A. Since the antibodies were found to have the same pattern of specificity, only one of them (E1) is described. This anti-CNPS monoclonal antibody reacted with the glucuronoxylomannan component of CNPS but not with the constituent monosaccharides or with the mannose alpha(1----3)-linked oligosaccharide structures present on CNPS. E1 appeared to be specific for C. neoformans serotype A by agglutination of whole cells; it was specific for soluble CNPS A by gel immunoprecipitation. However, indirect immunofluorescence and competitive-binding enzyme-linked immunosorbent assay experiments showed low levels of cross-reactivity with serotypes B and D but not with serotype C. Concentrations 10,000 times higher for serotypes B and D cells than for serotype A cells were required for a 50% inhibition of E1 anti-CNPS A activity as measured by enzyme-linked immunosorbent assay. Among the other yeasts tested, a cross-reaction was only detected with Trichosporon beigelii. The four serotypes of C. neoformans could be distinguished based on intensities and patterns of fluorescence in an indirect immunofluorescence assay using the monoclonal anti-CNPS A antibody. Monoclonal anti-CNPS A antibodies could be useful for fundamental studies on the glucuronoxylomannan structure, as well as for clinical applications such as serotyping and possibly the serological diagnosis of cryptococcosis.

Animals↗

Protection of mice against experimental cryptococcosis by anti-Cryptococcus neoformans monoclonal antibody.

Humoral immunity does not play a prominent role during experimental cryptococcosis. However, previous studies have shown that immunoglobulin G (IgG) anti-Cryptococcus neoformans antibodies can mediate cell-dependent yeast killing in vitro. Therefore, the protective effect of a previously described monoclonal IgG1 anti-C. neoformans antibody (E1) administered intraperitoneally 24 h before intravenous infection with a C. neoformans serotype A strain was evaluated in mice. Heavily infected (3 X 10(6) cells) untreated mice died in 2.9 +/- 0.5 (standard deviation) days. Survival time was 17.9 +/- 1.6 days for mice treated with 100 micrograms of E1 and 3.0 +/- 0.7 days for mice treated with 100 micrograms of a monoclonal IgG1 anti-thyroglobulin antibody used as a control. Protection was dose dependent and required at least 10 micrograms of E1 (mean antibody concentration in serum +/- standard deviation, 6.6 +/- 2.3 micrograms/ml). Insufficient concentrations of IgG anti-C. neoformans antibody could explain previous negative results obtained with polyclonal immune serum. After infection with a smaller inoculum (5 X 10(3) to 5 X 10(4)), the protective effect of E1 was confirmed by the presence of fewer CFUs in the spleens and brains of treated mice than in those of controls. CFU were still detected in the brains of protected mice 5 days after infection, although soluble antigen was negative in sera. These results suggest that passive serotherapy with monoclonal IgG antibodies could participate in the prevention or treatment of experimental cryptococcosis.

Animals↗

[Minimal etiological evaluation of Raynaud's phenomenon. 102 cases].

The efficacy of a minimal aetiological investigation program was tested in a population with Raynaud's phenomenon. The program had been devised to fulfill the following criteria: non invasive, simple and relatively cheap methods capable of detecting systemic scleroderma at an early stage. These methods turned out to be physical examination, screening for antinuclear antibodies, capillaroscopy and radiography of the hands and chest. After investigations which, in addition to the minimal program, included exploration of the digestive and respiratory tracts, heart, kidneys, articulations and eyes, 102 consecutive cases of Raynaud's phenomenon were studied and divided into 3 groups: idiopathic (n = 15); secondary (n = 50, including 36 cases of collagen disease, 29 of which were systemic scleroderma), and suspected idiopathic or pre-collagen disease (37 cases of undetermined origin but not considered idiopathic in view of clinical and/or paraclinical abnormalities). In non idiopathic Raynaud's phenomenon, physical examination, capillaroscopy and screening for antinuclear antibodies gave abnormal results in 96.5% of the cases. This figure was raised to 98.8% when radiography of the hands and chest was added to these 3 examinations, but the difference was not significant. Since 96.5% of non idiopathic Raynaud's phenomena could be diagnosed by physical examination, capillaroscopy and screening for antinuclear antibodies, it is suggested that all patients presenting with the phenomenon should be subjected to these three simple examinations; negative results then dispense from supplementary investigations.

Adolescent↗

Direct sensitive immunocharacterization of gangliosides on plastic thin-layer plates using peroxidase staining.

A technique for the immunocharacterization of gangliosides on thin-layer plates using a peroxidase-labelled anti-Ig antibody is described. The technique uses plastic plates and does not necessitate any transfer of the antigen onto nitrocellulose for immunodetection. Being extremely sensitive, it permits the characterization of gangliosides which cannot be detected by classical densitometric techniques and allows the detection of gangliosides even in trace amounts in ganglioside mixtures. It appears to be useful for the screening of monoclonal antibodies because of its rapidity. Its specificity was found to be analogous to other immunological techniques such as complement fixation and agglutination.

Antibody Specificity↗

Cryoprecipitation of an anti-Pr2 monoclonal IgM cold agglutinin in the presence of GM3 ganglioside.

The mechanism of cryoprecipitation of a monoclonal IgM kappa cryoglobulin (Mou) with a cold agglutinin activity of Pr2 specificity has been studied. By immunodiffusion this cryoglobulin reacted (by its Fab' fragment) with micellar GM3, a ganglioside bearing the Pr2 antigenic determinant. In contrast to previous reports that indicated a possible temperature dependent self-association of IgM molecules via an immunological interaction leading to cold precipitation, we could not detect any affinity of this cryoglobulin for IgM when we used passive hemagglutination or an indirect enzyme-linked immunosorbent assay (ELISA). However, a GM3-like ganglioside could be extracted, by drastic methods, from the cryoglobulin studied at 22 degrees C, whereas no GM3 was extracted from two control cryoglobulins. Some minor gangliosides (representing less than 25% of total amount of bound gangliosides) were also extracted from Mou cryoglobulin and these gangliosides were shown to crossreact with GM3, as they specifically bind to Mou cryoglobulin by ELISA. After cryoprecipitation the serum still contained a monoclonal anti-Pr2 IgM kappa. A GM3-like ganglioside could be extracted from this purified IgM, and cryoprecipitability could be induced by the addition of a minute amount of micellar GM3. These results suggest that Mou cryoglobulin circulates as an immune complex and that cryoprecipitation may depend on unique IgM-GM3 (or IgM-GM3 cross-reacting gangliosides) complexes.

Agglutinins↗

[Theoretical objective evaluation of the value of a diagnostic criterion. Application to antinuclear antibodies for the diagnosis of systemic lupus erythematosus].

The value of various types of anti-nuclear antibodies (ANA) for the diagnosis of systemic lupus erythematosus (SLE) was calculated in a population of adult patients with chronic polyarthritis. The aim of this study was to demonstrate the value of calculating the predictive value of a test applied to a particular clinical situation. It was conducted on the basis of epidemiological and laboratory data from the literature. The calculations show that the presence of ANA in immunofluorescence only slightly increases the probability of the diagnosis of SLE (7%). On the other hand, these antibodies are an example of a very sensitive test which, when it is negative allows the diagnosis to be almost totally excluded, while anti-Sm antibodies are very specific and their presence allows the diagnosis to be confirmed. Anti-nDNA antibodies have intermediate features, but their diagnostic performance increases with the level of radioactive n-DNA binding chosen as the level of positivity; in this example, for a level of binding of more than 50%, the predictive value of anti-nDNA antibodies is equivalent to that of anti-Sm antibodies.

Adult↗

[Study of thyroid autoimmunity in man. Contribution of cell cultures to the study of antibodies stimulating the thyroid gland in Basedow's disease].

The value of thyroid cell cultures in vitro has been demonstrated in auto-immune thyroiditis in animals. We have used the same method in man to investigate for serum thyroid-stimulating antibodies (TSAb) by measuring cyclic AMP production in thyroid cell cultures incubated with immunoglobulins from patients with Graves' disease. The specificity of the reaction is strictly directed either against TSH or against immunoglobulins from patients with Graves' disease; 92% of the sera of our untreated Graves' disease patients were positive. The value of this technique compared to the other methods used for detecting TSAb is discussed.

Adolescent↗

[Late recurrence of Horton's disease with sicca syndrome].

The authors report the case of an eighty-three-year-old woman with giant-cell arteritis who experienced recurrence five years after the withdrawal of corticosteroids which had been given for four consecutive years. This recurrence, demonstrated by arterial biopsy, was accompanied with Sjögren disease proven upon histological examination. With reference to this case-report, the various possible courses of protracted giant-cell arteritis are discussed; relapses occurring more than one year after therapy is discontinued are exceptional.

Aged↗

Characterization by human autoantibody of a nuclear antigen related to the cell cycle.

Using a serum from a patient with an autoimmune disease, we have recently described a novel 55 000-dalton antigen (p55) in the nucleus of several animal cells including human ones. This antigen, designated PSL, was not related to the previously defined antigens recognized by sera from patients with systemic rheumatic diseases (Sm, n-RNP, SS-B, Scl-70). We have now found that p55 is associated with chromatin structures as it is released from the nucleus of mink cell fibroblasts by saline + DNase treatments. Analysis by sucrose gradient centrifugation of the nuclear material released in these conditions indicated that p55 co-migrated with core histones. Meanwhile, p55 was absent from the residual nuclear matrices (achromatinic nuclei). Localization of p55 in synchronized cells was performed by indirect immunofluorescence and immunoprecipitation. P55 appeared to accumulate in the nucleus during the S phase. Finally, it was not recognized by an anti-SV40 tumor serum that specifically precipitated the protein p53, which has been recently related to cell proliferation. Thus, PSL an p53, although apparently not antigenically related, appear to be implicated in the same step of the cell cycle.

Animals↗

Serum levels of antibody to toxoid during tetanus and after specific immunization of patients with tetanus.

Levels of serum antibody to toxoid in patients with tetanus who were immunized with toxoid differed from those in immunized healthy persons in two respects. (1) Base-line levels preceding immunization were higher among patients with tetanus than among young or elderly healthy person, even though the patients with tetanus were evaluated before specific serotherapy. This observation suggests the occurrence of immunostimulation, whether specific or not, by disease during the incubation period. (2) No significant increase in levels of antibody to toxoid was detected among patients with tetanus from the first to the last evaluable serum sample, whereas a significant increase was observed among healthy persons. Specific immunosuppression induced by tetanus toxoid or serotherapy could account for this ineffectiveness of immunization among patients with tetanus, although nonspecific immunosuppression induced by prolonged and severe illness cannot be excluded. Among healthy persons, active immunization is less effective in elderly persons than in young persons [2]. However, age cannot, by itself, account for the type of antibody production observed in patients with tetanus.

Adult↗