PubMed · 10635817
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T Hamamoto. 1999. [Candida].. https://pubmed.ncbi.nlm.nih.gov/10635817/
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The Ura2 multidomain protein catalyses the first two steps of pyrimidines biosynthesis in Saccharomyces cerevisiae. It consists of a 240 kDa polypeptide which contains carbamyl phosphate synthetase and aspartate transcarbamylase domains. The Ura2 protein was believed to be nucleoplasmic, since one of the aspartate transcarbamylase reaction products, monophosphate, was reported to be precipitated by lead ions inside nuclei. However, this ultracytochemical approach was recently shown to give artifactual lead polyphosphate precipitates, and the use of cerium instead of lead failed to reveal this nucleoplasmic localization. Ura2 localization has therefore been undertaken by means of three alternative approaches based on the detection of the protein itself: (a) indirect immunofluorescence of yeast protoplasts; (b) immunogold labelling of ultrathin sections of embedded yeast cells (both approaches using affinity purified primary antibodies directed against the 240 kDa Ura2 polypeptide chain, or against a 22 residue peptide specific of the carbamyl phosphate synthetase domain); and (c) direct fluorescence of cells expressing an Ura2-green fluorescent protein hybrid. All three approaches localize the bulk of Ura2 to the cytoplasm, whereas the signals associated with the nucleus, mitochondria or vacuoles are close to or at the background level.
Fungal infections continue to cause major complications in cancer patients. With the increasing use of aggressive chemotherapy and stem cell transplantation causing profound, prolonged depressed immunity, the risk of invasive mycoses has increased. The prognosis of these infections is poor unless they are diagnosed and treated promptly. The management of opportunistic fungal infections is characterized by a series of unresolved problems, including initial difficulties in obtaining an early diagnosis. Clinical signs indicating a definite diagnosis of fungal infection is frequently absent in cancer patients. There are no distinctive symptoms and fever is the most common and, frequently, the only sign. In only a minority of cases, and usually after recovery from neutropenia, can some clinical features, such as pulmonary pseudomycetoma and hepatosplenic lesions, be suggestive of an invasive mycosis. Thus, laboratory procedures are necessary to reveal or confirm the diagnosis of invasive mycosis and establish disease etiology. Cultures are often negative and positive results need a careful evaluation to determine clinical importance. The significance of fungi isolated from mucosal surfaces and from the respiratory tract in diagnosing invasive mycoses is controversial. The problem in interpreting these microbiological data is the differentiation between fungal infection and colonization. Detection of fungal antigens by molecular methods appears to be promising, but the significance in various clinical settings is still under evaluation. In most cases, the diagnosis depends on a combination of clinical, microbiological, histological and serological results.
We have previously demonstrated that exogenous Nef protein induced activation of normal human T cells up-regulating IL-15 production by monocytes. Since HIV-1 infection results in the early impairment of immune functions we decided to evaluate if Nef is able to modulate the induction of a specific antibody response. Human peripheral blood mononuclear cells from healthy donors were induced in vitro to mount a specific antibody response to the Candida albicans antigen. We show that Nef inhibited, in a dose-dependent manner, the induction of the anti-C. albicans antibody response. The ability of an anti-Nef antibody to prevent such inhibition indicates that the effect was indeed Nef-specific. In the Nef-treated cultures an early increase of IL-15 production was observed and the addition of anti-IL-15 antibody abrogated the Nef-induced inhibitory effect. Moreover the addition of IL-15 to the cultures inhibited, as well as Nef, the induction of the specific antibody response. Thus, our results suggest that Nef may inhibit the induction of a specific antibody response by an early up-regulation of IL-15 production. A better comprehension of this phenomenon may be important for unravelling some aspects of the B cell defects in HIV infection.