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A Cassone

Publications and source records attributed to A Cassone.

At least 127 records · Page 7Linked to original sources
PubMed1990

Evidence for a role for secreted aspartate proteinase of Candida albicans in vulvovaginal candidiasis.

The presence of the secretory aspartate (acid) proteinase in the vaginal fluid of candidal vaginitis patients and controls was studied by ELISA and immunoblot (Western blot). In addition, a proteinase-deficient mutant strain of Candida albicans (IR24) was compared with the wild-type parent strain (10261) for ability to infect the vagina of pseudoestrus rats under estradiol treatment. Among the 67 women examined, proteinase was detected only in 22 harboring C. albicans (range, 42-233 ng/ml of vaginal fluid), at concentrations significantly higher in the 14 vaginitis patients than in the 8 asymptomatic fungal carriers. Western blots confirmed the presence of only one protein band of approximately 43 kDa, corresponding to that of the purified proteinase, in the ELISA-positive vaginal fluids. Experimental vaginal infection was significantly more extensive and persistent in rats infected with the proteinase-producer strain than in those challenged with the proteinase-deficient mutant, and the enzyme was detected in the vaginas of the former but not of the latter animals. Both strains 10261 and IR24 developed hyphal forms to a roughly similar extent during infection, and both showed a comparable adherence in vitro to vaginal and buccal epithelial cells. The clinical and experimental evidence support a role for secretory proteinase as a virulence factor in the pathogenesis of candidal vaginitis.

Adult↗
PubMed1990

Lymphoproliferative and cytotoxic responses of human peripheral blood mononuclear cells to mannoprotein constituents of Candida albicans.

Two major proteoglycan constituents (designated F1 and F2) of the cell wall of Candida albicans were separated by ion-exchange chromatography from a crude carbohydrate-rich extract (GMP), and investigated for their chemical and molecular composition, antigenicity and immunomodulatory properties in cultures of human peripheral blood mononuclear cells (PBMC). Both fractions consisted predominantly of Periodic acid-Schiff (PAS) and concanavalin A (Con A)-reactive material consisting of greater than 90% mannose, 3-5% protein and small amounts of phosphorus; each was recognized by an anti-Candida rabbit serum as well as by a monoclonal antibody (mAb AF1) directed against an oligosaccharide epitope present on the fungal cell surface. When F1 and F2 were subjected to SDS-PAGE, transblotted and stained with enzyme-conjugated mAb AF1 or Con A, most of the antibody or lectin bound to high molecular mass (greater than 200 kDa) polydisperse material, some of which was present in F2 (as in the starting GMP extract) but absent in F1. This difference was also observed in PAS-stained gels of the two fractions. The F2, but not the F1, constituent was as active as the unfractionated GMP extract in inducing lymphoproliferation, production of the cytokines interleukin-2 and interferon-gamma, and generation of cytotoxicity against a natural-killer-sensitive target cell line (K562). These immunomodulatory properties were, like those possessed by GMP, protease-sensitive and heat-stable. Treatment of PMBC cultures with a modulatory anti-T-cell receptor antibody abolished the lymphoproliferation induced by GMP and F2 but not that induced by phytohaemagglutinin, showing that the mannoprotein materials of C. albicans acted through interaction with the antigen receptor complex.

Antibodies, Monoclonal↗
PubMed1990

The secreted aspartate proteinase of Candida albicans: physiology of secretion and virulence of a proteinase-deficient mutant.

It was established that Candida albicans grew rapidly in a simple medium containing yeast extract (0.2%, w/v) plus glucose (2%, w/v). These cultures were in or near to a state of nitrogen limitation and the concentration of secreted aspartate proteinase increased rapidly (within 3-4 h) on addition of BSA. Synthesis and secretion were apparently controlled both positively (induction by albumin or, more probably, the peptides produced from it) and negatively (repression by NH4Cl). A small intracellular pool of the enzyme was detected during production of the enzyme and this pool decreased with the cessation of synthesis and secretion. A stable mutant, IR24, was isolated which secreted less than 0.3% of the amount of the proteinase exported by the parent strain ATCC 10261. The LD50 values for mutant IR24 and the parent strain administered intravenously to mice were greater than 1.0 x 10(9) and 1.6 x 10(6) c.f.u. kg-1 respectively.

Animals↗
PubMed1990

Differences in the antigenic expression of immunomodulatory mannoprotein constituents on yeast and mycelial forms of Candida albicans.

The expression of a strongly immunomodulatory mannoprotein complex (GMP) in the different forms of growth of the human commensal and opportunistic pathogen Candida albicans was studied using a monoclonal antibody (mAb AF1) directed against an oligosaccharide epitope of GMP. Immunofluorescence revealed that the surface of the yeast cells was highly reactive with mAb AF1, but that the reactivity was greatly reduced or disappeared during mycelial conversion. This modulation was shared by a number of strains of C. albicans, and was not solely a temperature- or nutrition-dependent phenomenon. Hypha-deficient strains (A12 and CA2) did not show variations of surface fluorescence under environmental conditions which were permissive for hyphal conversion (incubation in N-acetylglucosamine or Lee's medium, at 37 degrees C). GMP extracts from yeast and mycelial forms of the fungus were separated into three chromatographically distinct, high molecular mass mannoprotein fractions (F1, F2 and F3), which were tested individually by indirect ELISA for mAb AF1 recognition. All yeast-derived constituents and two (F2 and F3) of the hyphal mannoproteins were recognized by the mAb. The low or absent reactivity of the F1 constituent from hyphal cells was confirmed by immunoblots. Irrespective of their source (yeast or mycelial), all fractions reacted to a similar extent with a polyclonal anti-Candida serum. Overall, the data suggest changes in epitope specificity and/or confinement of reactive constituents in the inner wall layers as possible mechanisms of modulated expression of mAb AF1-reactive epitope during mycelial conversion.

Agglutination Tests↗
PubMed1989

Prevalence of non-specific vaginitis and correlation with isolation of Gardnerella vaginalis in Italian outpatients.

Among all subjects attending a Center for prevention of female genital tract cancer Gardnerella vaginalis was isolated from 57 out of 171 women affected by non-specific vaginitis (NSV), from 15 of 703 non-NSV vaginitis patients and from 10 of 338 healthy adults. Postmenopausal women showed an increased rate of asymptomatic carriage of G. vaginalis. The data suggest a relatively weak association between clinical diagnosis of NSV and isolation of G. vaginalis.

Adolescent↗
PubMed1989

Cytotoxic effectors in human peripheral blood mononuclear cells induced by a mannoprotein complex of Candida albicans: a comparison with interleukin 2-activated killer cells.

In this study, the major histocompatibility complex-unrestricted cytotoxic effectors elicited in human peripheral blood mononuclear cells (PBMC) by a mannoprotein (MP) component from the cell wall of the human indigenous microorganism Candida albicans have been compared with those obtained by stimulation with interleukin 2. (Interleukin 2-activated killer cells: LAK). It has been found that MP-induced lytic effectors were substantially similar to LAK in potency, target specificity, and type of precursor/effector cells. In both cases, natural killer (NK)-susceptible and NK-resistant targets as well as fresh tumor (glioma) cells were efficiently killed by a population of effectors showing a predominant CD3-, CD16+ phenotype. However, the precursors of MP-induced killers were highly sensitive to the lysosomotropic toxic drug L-leucine methyl ester (Leu-OME) whereas the generation of LAK cells was unaffected by this drug. The Leu-OME sensitivity of MP-induced cytotoxicity generation was not due to a nonspecific effect on antigen-presenting cells or inhibition of cell proliferation. In addition, the generation of MP-induced killer cells was totally abrogated by treatment with CD16 antibodies and complement, whereas a minor but significant fraction of LAK precursors was not susceptible to the above treatment. These results indicate that a defined component(s) of the cell wall of C. albicans has some properties of biological response modifiers in cultures of human PBMC in vitro.

Antigens, Surface↗
PubMed1989

Protective immunity induced by low-virulence Candida albicans: cytokine production in the development of the anti-infectious state.

A low-virulence, agerminative strain of Candida albicans (PCA-2) is able to confer a high degree of nonspecific protection against subsequent challenge with highly virulent microorganisms in mice. In an attempt to better define the effect of PCA-2 vaccination on the immune system and the nature of the mechanisms involved in this protective state, we evaluated the pattern and kinetics of production of selected cytokines in PCA-2-treated mice. Thus, granulocyte/monocyte colony-stimulating factor (GM-CSF), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and interleukin 1 (IL-1) were measured in the sera and spleen cell supernatants of vaccinated mice. In both cases, high levels of CSF, TNF, IL-1, and IFN were found 6 hr after PCA-2 infection and persisted for many days. There was always a correlation between the ability of PCA-2 to induce antimicrobial protection in vivo and its ability to cause cytokine production in vitro. Supernatants of splenocyte cultures from PCA-2-infected animals possessed macrophage-activating activity, as measured in microbiological assays. These data suggest an important involvement of cytokines in the nonspecific anti-infectious immunity induced by PCA-2, and also suggest a crucial role for IL-1 as an endogenous adjuvant in the initiation of the immune response to PCA-2.

Amphotericin B↗
PubMed1989

Experimental rat vaginal infection with Candida parapsilosis.

The experimental vaginopathic potential of Candida parapsilosis was determined in ovariectomized rats maintained under pseudoestrus by estrogen administrations. Of the 3 strains of C. parapsilosis tested, that isolated from the vagina of a woman affected by vulvovaginal candidosis gave a prolonged and sustained experimental vaginitis, not different in extent and duration from that caused by a vaginal isolate of C. albicans from a vaginitis patient. The other two isolates of C. parapsilosis (one from the vagina of an asymptomatic subject and another from soil) were unable to infect rat vagina. Microscopic observations of PAS-stained vaginal smears from rats infected with the vaginopathic isolate of C. parapsilosis showed pronounced adherence of yeasts to exfoliated cells. In addition, this isolate of C. parapsilosis produced an elevated quantity of acid proteinase in vitro.

Animals↗
PubMed1989

Isolation, acid proteinase secretion, and experimental pathogenicity of Candida parapsilosis from outpatients with vaginitis.

Candida parapsilosis was isolated from the vaginas of several nonpregnant, nondiabetic, mostly premenopausal outpatients who presented the characteristic signs and symptoms of a frank vulvovaginal candidiasis (heavy discharge with cottage cheese appearance and intense itching, with or without vulvar erythema and dyspareunia). All isolates conformed morphologically, biochemically, and serologically to the standard description of the species. They showed high acid proteinase-secretory activity in vitro and were appreciably pathogenic for cyclophosphamide-immunodepressed mice. Some isolates were also tested for their vaginopathic potential in ovariectomized rats under estradiol administration. In all cases, the rat vagina was colonized by C. parapsilosis to an extent and duration not different from those caused by a vaginopathic isolate of Candida albicans. Periodic acid-Schiff-stained vaginal smears taken at intervals during rat experimental infection showed C. parapsilosis yeasts adhering to exfoliated epithelial cells of rat vagina. Overall, these results emphasize the proteolytic and pathogenic potential of C. parapsilosis and suggest that this fungus may be an agent of clinical vaginitis.

Animals↗
PubMed1989

[Gardnerella vaginalis: role of a microorganism emerging as a vaginopathic agent and its placement in the vaginal microbial ecosystem].

In this review the role of an emergent pathogen, Gardnerella vaginalis (G. vaginalis), as aetiologic agent of the so called "non specific vaginitis" is systematically evaluated. The microorganism is described in its morphological, biochemical and virulence aspects in the framework of the complex vaginal ecosystem. The diagnostic criteria of the disease as well as a possible association of G. vaginalis with other vaginal bacteria, especially anaerobes, in the aetiology of the disease, are discussed. Literature data on prevalence and incidence of G. vaginalis in different population groups are integrated by more recent investigations of the Authors on prevalence and carriage of microorganism in a group of outpatients in Italy.

Adolescent↗
PubMed1988

The response of peripheral blood mononuclear cells of glioma-bearing patients to stimulation with microbial antigen and IL-2: proliferation and IFN-gamma production.

Peripheral blood mononuclear cells (PBMC) of malignant glioma-bearing patients were stimulated in vitro with a glucomannan-protein antigen of Candida albicans (GMP) or Interleukin-2 (IL-2), then assayed for proliferation and production of Interferon gamma. PBMC of healthy, age and sex matched subjects were the controls. PBMC from glioma-bearing patients did not differ, as a whole, from PBMC of healthy donors in IL-2 or GMP-induced proliferation. However, they showed a definitely lesser ability to produce IFN. The results are discussed in the framework of the impairment of immune responses known to affect glioma-bearing patients.

Antigens, Fungal↗
PubMed1988

Cell-mediated cytotoxicity in glioma-bearing patients: differential responses of peripheral blood mononuclear cells to stimulation with interleukin-2 and microbial antigen.

Peripheral blood mononuclear cells (PBMC) of malignant glioma-bearing patients were stimulated in vitro with Interleukin-2 (IL-2) or a glucomannan-protein antigen of Candida albicans (GMP) then assayed for proliferation, production of IFN-gamma, and generation of cytotoxic effectors against either K562 tumor cell line or freshly-cultured allogenic glioma cells. PBMC of healthy, age and sex-matched subjects were the controls. PBMC of glioma-bearing patients did not differ, as a whole, from PBMC of healthy donors in IL-2 or GMP-induced proliferation. However, they showed a lesser ability to produce IFN as well as a substantial inability to generate cytotoxic effectors following GMP stimulation. PBMC of glioma patients were fully responsive to IL-2 in cytotoxicity generation, as were the PBMC from normal subjects. The results suggest that glioma patients may have a defective antigen-mediated activation of natural cytotoxic effectors. This hyporesponsiveness is not accompanied by depressed lymphoproliferation and does not apparently involve a reduced response to IL-2.

Adult↗
PubMed1988

Immunomodulation by a low-virulence, agerminative variant of Candida albicans. Further evidence for macrophage activation as one of the effector mechanisms of nonspecific anti-infectious protection.

Systemic infection of mice with a Candida albicans strain (PCA-2) incapable of yeast-mycelial conversion is known to activate host macrophages and confer protection against subsequent challenge with highly pathogenic cells of the same species or by other micro-organisms. In an attempt to define the relative contributions of different immune components to the protection mediated by PCA-2, we evaluated the effect of manipulations known to selectively deplete immune functions. By means of cytostatic drug or silica induced toxicity, it was possible to demonstrate that no crucial role in protection is played by cytotoxic T lymphocytes or B cells, nor by PCA-2 induced granulocytosis alone. The cells responsible for this effect were dacarbazine-resistant silica-sensitive macrophages whose activity in vivo paralleled the in vitro expression of splenic candidacidal activity. Macrophage activation by PCA-2 and increased anti-Candida resistance did not result from an immunological response mediated by T-dependent effectors, as these effects could be reproduced in athymic mice.

Adjuvants, Immunologic↗