Human papillomavirus types 52 and 58 are prevalent in cervical cancer from Chinese women.
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Carcinoma, Squamous Cell↗
Biomedical subjects
T Zhang
Publications and source records attributed to T Zhang.
Protection against invasive amebiasis by a single monoclonal antibody directed against a lipophosphoglycan antigen localized on the surface of Entamoeba histolytica.
A panel of monoclonal antibodies was raised from mice immunized with a membrane preparation from Entamoeba histolytica, the pathogenic species causing invasive amebiasis in humans. Antibody EH5 gave a polydisperse band in immunoblots from membrane preparations from different E. histolytica strains, and a much weaker signal from two strains of the nonpathogenic species Entamoeba dispar. Although the exact chemical structure of the EH5 antigen is not yet known, the ability of the antigen to be metabolically radiolabeled with [32P]phosphate or [3H]glucose, its sensitivity to digestion by mild acid and phosphatidylinositol-specific phospholipase C, and its specific extraction from E. histolytica trophozoites by a method used to prepare lipophosphoglycans from Leishmania showed that it could be classified as an amebal lipophosphoglycan. Confocal immunofluorescence and immunogold labeling of trophozoites localized the antigen on the outer face of the plasma membrane and on the inner face of internal vesicle membranes. Antibody EH5 strongly agglutinated amebas in a similar way to concanavalin A (Con A), and Con A bound to immunoaffinity-purified EH5 antigen. Therefore, surface lipophosphoglycans may play an important role in the preferential agglutination of pathogenic amebas by Con A. The protective ability of antibody EH5 was tested in a passive immunization experiment in a severe combined immunodeficient (SCID) mouse model. Intrahepatic challenge of animals after administration of an isotype-matched control antibody or without treatment led to the development of a liver abscess in all cases, whereas 11 out of 12 animals immunized with the EH5 antibody developed no liver abscess. Our results demonstrate the importance and, for the first time, the protective capacity of glycan antigens on the surface of the amebas.
Animals↗
Cryptococcus neoformans inhibits nitric oxide production by murine peritoneal macrophages stimulated with interferon-gamma and lipopolysaccharide.
We examined the effect of Cryptococcus neoformans on nitric oxide (NO) production by activated cultured macrophages. C. neoformans suppressed NO production by murine peritoneal macrophages stimulated with bacterial lipopolysaccharide (LPS) and interferon (IFN)-gamma, while it did not influence the production of IL-1 beta. This effect was observed when 1 x 10(6) or 10(7) of C. neoformans was added to macrophage cultures. A direct contact of C. neoformans with macrophages was essential for this inhibitory effect, since placement of a 0.45-micron-pore membrane between the organism and macrophages prevented such effect. In addition, C. neoformans killed by heat or paraformaldehyde did not show this inhibitory activity. Capsular polysaccharide did not mediate the inhibitory effect, since two nonencapsulated mutant strains of C. neoformans showed an inhibitory activity similar to that of encapsulated wild strains, and culture supernatants of C. neoformans, rich in polysaccharide antigens, did not inhibit macrophage NO production compared with control culture medium. The inhibitory effect was also not mediated by interleukin (IL)-10 and transforming growth factor (TGF)-beta since neutralizing specific antibodies to these cytokines did not influence C. neoformans-induced reductions in macrophage NO production. Our results suggest that C. neoformans may cause a direct suppression of NO-mediated fungicidal activity of macrophages, and the effect is independent of the capsular polysaccharide and production of IL-10 and TGF-beta.
Animals↗
GS15, a 15-kilodalton Golgi soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) homologous to rbet1.
Bet1p plays an essential role in vesicular transport from the endoplasmic reticulum (ER) to the Golgi in yeast, and it functions as a vesicle soluble N-ethylmaleimide-sensitive factor protein receptor (v-SNARE). A mammalian protein related to Bet1p has been reported previously and was referred to as rbet1. We have now identified a new mammalian protein that is homologous to rbet1 (28% amino acid identity). mRNA for this rbet1 homologue is widely expressed in rat tissues. Affinity-purified polyclonal antibodies raised against recombinant protein specifically recognized a 15-kilodalton integral membrane protein highly enriched in Golgi membranes. Indirect immunofluorescence microscopy revealed that this protein is specifically associated with the Golgi apparatus in diverse cell types. Biochemical characterization established that this protein behaves like a SNARE and was named GS15 (Golgi SNARE with a size of 15 kilodaltons). These properties raise the possibility that GS15 is a novel SNARE mediating a yet to be defined transport event associated with the Golgi apparatus.
Amino Acid Sequence↗
The mouse Fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation.
Mutations at the mouse Fused locus have pleiotropic developmental effects, including the formation of axial duplications in homozygous embryos. The product of the Fused locus, Axin, displays similarities to RGS (Regulators of G-Protein Signaling) and Dishevelled proteins. Mutant Fused alleles that cause axial duplications disrupt the major mRNA, suggesting that Axin negatively regulates the response to an axis-inducing signal. Injection of Axin mRNA into Xenopus embryos inhibits dorsal axis formation by interfering with signaling through the Wnt pathway. Furthermore, ventral injection of an Axin mRNA lacking the RGS domain induces an ectopic axis, apparently through a dominant-negative mechanism. Thus, Axin is a novel inhibitor of Wnt signaling and regulates an early step in embryonic axis formation in mammals and amphibians.
Amino Acid Sequence↗
Evolution of HIV-1 coreceptor usage through interactions with distinct CCR5 and CXCR4 domains.
The chemokine receptor CXCR4 functions as a fusion coreceptor for T cell tropic and dual-tropic HIV-1 strains. To identify regions of CXCR4 that are important for coreceptor function, CXCR4-CXCR2 receptor chimeras were tested for the ability to support HIV-1 envelope (env) protein-mediated membrane fusion. Receptor chimeras containing the first and second extracellular loops of CXCR4 supported fusion by T tropic and dual-tropic HIV-1 and HIV-2 strains and binding of a monoclonal antibody to CXCR4, 12G5, that blocks CXCR4-dependent infection by some virus strains. The second extracellular loop of CXCR4 was sufficient to confer coreceptor function to CXCR2 for most virus strains tested but did not support binding of 12G5. Truncation of the CXCR4 cytoplasmic tail or mutation of a conserved DRY motif in the second intracellular loop did not affect coreceptor function, indicating that phosphorylation of the cytoplasmic tail and the DRY motif are not required for coreceptor function. The results implicate the involvement of multiple CXCR4 domains in HIV-1 coreceptor function, especially the second extracellular loop, though the structural requirements for coreceptor function were somewhat variable for different env proteins. Finally, a hybrid receptor in which the amino terminus of CXCR4 was replaced by that of CCR5 was active as a coreceptor for M tropic, T tropic, and dual-tropic env proteins. We propose that dual tropism may evolve in CCR5-restricted HIV-1 strains through acquisition of the ability to utilize the first and second extracellular loops of CXCR4 while retaining the ability to interact with the CCR5 amino-terminal domain.
Cell Fusion↗
Surface Activity of ABA-Type Nonionic Oligosaccharide Surfactants
We report on the surface activity of two novel ABA-type nonionic oligosaccharide surfactants: N,N '-dodecamethylene-bismaltonamide and N,N '-dodecamethylene-bis(dextran aldonamide) (DEX-C12-DEX). Surface active properties, determined from surface tension measurements, were compared with results for AB-type counterparts containing the same hydrophobic segment, N -dodecylmaltonamide and N -dodecyl dextran aldonamide (DEX-C12). Surface tension measurements, including analysis of binary surfactant mixtures of DEX-C12 and DEX-C12-DEX show that the DEX-C12-DEX does not form micelles, but induces micelle formation of DEX-C12 at a critical total surfactant concentration and diblock mole fraction. We show the effects of oligosaccharide chain length and molecular geometry on surface activity and packing density and, with the aid of molecular models, discuss our results from the viewpoint of surfactant conformation.
Journal Article↗
Identification of an epitope on the Entamoeba histolytica 170-kD lectin conferring antibody-mediated protection against invasive amebiasis.
The emergence of multidrug-resistant organisms and the failure to eradicate infection by a number of important pathogens has led to increased efforts to develop vaccines to prevent infectious diseases. However, the nature of the immune response to vaccination with a given antigen can be complex and unpredictable. An example is the galactose- and N-acetylgalactosamine-inhibitable lectin, a surface antigen of Entamoeba histolytica that has been identified as a major candidate in a vaccine to prevent amebiasis. Vaccination with the lectin can induce protective immunity to amebic liver abscess in some animals, but others of the same species exhibit exacerbations of disease after vaccination. To better understand this phenomenon, we used recombinant proteins corresponding to four distinct domains of the molecule, and synthetic peptides to localize both protective and exacerbative epitopes of the heavy chain subunit of the lectin. We show that protective immunity after vaccination can be correlated with the development of an antibody response to a region of 25 amino acid residues of the lectin, and have confirmed the importance of the antibody response to this region by passive immunization studies. In addition, we show that exacerbation of disease can be linked to the development of antibodies that bind to an NH2-terminal domain of the lectin. These findings are clinically relevant, as individuals who are colonized with E. histolytica but are resistant to invasive disease have a high prevalence of antibodies to the protective epitope(s), compared to individuals with a history of invasive amebiasis. These studies should enable us to develop an improved vaccine for amebiasis, and provide a model for the identification of protective and exacerbative epitopes of complex antigens.
Amino Acid Sequence↗
Decreased transforming growth factor beta type II receptor expression in intestinal adenomas from Min/+ mice is associated with increased cyclin D1 and cyclin-dependent kinase 4 expression.
Tumor cells often become resistant to the growth-inhibitory effects of transforming growth factor beta (TGF-beta). Recent studies have identified TGF-beta type II receptor (RII) mutations in a subset of cancers, including colon cancer. To evaluate the expression of TGF-beta RII in premalignant intestinal adenomas and the relationship with cell cycle regulation, we investigated the expression of TGF-beta RII, cyclin D1, and cyclin-dependent kinase 4 (Cdk4) in Min/+ mouse intestinal adenomas. Immunohistochemistry indicated that TGF-beta RII cytoplasmic immunoreactivity was undetectable in the proliferative crypt zones of the normal small intestinal and normal colonic epithelium but was abundant toward the villus tips of the normal small intestine and the lumenal third of the colonic glands. As was observed in the proliferating crypt zones, TGF-beta RII immunoreactivity was dramatically decreased or undetectable in all adenomas examined in comparison to the abundant levels in adjacent normal differentiated intestinal epithelium. TGF-beta RII mRNA was also reduced in the adenomas in comparison to normal mucosa as determined by reverse transcription-PCR. In an inverse distribution to TGF-beta RII, Cdk4 nuclear immunoreactivity was restricted to the crypt regions of the small and large intestine, whereas cyclin D1 immunoreactivity was uniformly absent in normal intestinal epithelium. For both cyclin D1 and Cdk4, protein and mRNA levels were increased in intestinal adenomas but not in normal intestinal epithelium as determined by immunohistochemistry, in situ hybridization, and reverse transcription-PCR. In summary, the lack of TGF-beta RII expression was associated with increased cyclin D1 and Cdk4 expression in Min/+ mouse intestinal adenomas. We hypothesize that the former may enable tumor cells to escape from the normal growth-constraining influence of TGF-beta, whereas the latter promotes inappropriate cell proliferation and adenoma progression.
Adenoma↗
Concurrent overexpression of cyclin D1 and cyclin-dependent kinase 4 (Cdk4) in intestinal adenomas from multiple intestinal neoplasia (Min) mice and human familial adenomatous polyposis patients.
We postulated that increased expression of the cell cycle regulators cyclin D1 and cyclin-dependent kinase (Cdk) 4 may be involved in the development of intestinal adenomas associated with familial adenomatous polyposis (FAP). In the present study of multiple intestinal neoplasia (Min) mice and human FAP patients, the expression and distribution of cyclin D1, Cdk4, and cell proliferative activity (5-bromo-2'-deoxyuridine incorporation) in normal and adenomatous intestinal epithelium were investigated. Immunohistochemical analysis of Min mouse intestine revealed that cyclin D1 immunoreactivity in the intestinal epithelium was restricted to the adenomatous areas, with a significantly higher percentage of positively staining nuclei in high-grade dysplasia versus low-grade dysplasia (54.8 +/- 18.4% versus 34.6 +/- 16.9%, P = 0.016). Morphologically normal areas of intestinal epithelia were uniformly negative for cyclin D1 immunoreactivity. Cdk4 nuclear immunoreactivity was restricted to the crypt areas in morphologically normal small intestine and colon. Conversely, Cdk4 immunoreactivity was uniformly abundant in adenomatous areas regardless of the degree of dysplasia. Increased expression of cyclin D1 and Cdk4 in adenomas was accompanied by a significantly increased 5-bromo-2'-deoxyuridine incorporation rate in the same areas. Immunoblot analysis of lysates from surgical specimens revealed increased levels of cyclin D1 and Cdk4 in the majority of intestinal adenomas from human FAP patients in comparison to the adjacent grossly normal colonic mucosa. Our results indicate that overexpression of cyclin D1 and Cdk4 occurs in intestinal adenomas and is associated with increased cell proliferative activity in premalignant neoplastic cells. Increased cyclin D1 immunoreactivity is associated with more severe dysplasia. These data suggest that abnormal up-regulation of these important G1 cell cycle proteins is a relatively early event in intestinal carcinogenesis and that these changes may contribute to malignant progression within those lesions.
Adenomatous Polyposis Coli↗
Comparison of inactivation and conformational changes of aminoacylase during denaturation in lithium dodecylsulphate solutions.
The denaturation of aminoacylase in LDS solutions of different concentrations has been studied by following the changes in the ultraviolet absorbance, circular dichroism and intrinsic fluorescence. The results obtained show that the denaturation of the enzyme results in negative peaks at 287 and 295 nm in the denatured minus native enzyme difference spectrum. The fluorescence emission intensify of the enzyme decreases with no red shift of emission maximum in LDS solutions of increasing concentrations. In the LDS concentration regions employed in present study, no marked changes of secondary structure of the enzyme have been observed by following the changes in far ultraviolet CD spectra. The inactivation of this enzyme has been followed and compared with the unfolding observed during denaturation in LDS solutions. A marked inactivation is already evident at low LDS concentrations before signification conformational changes can be detected by ultraviolet absorbance and fluorescence changes. The inactivation rate constants of free enzyme and substrate-enzyme complex were determined by the kinetics method of the substrate reaction in the presence of inactivator previously described by Tsou. At the same LDS concentrations, the inactivation rate constants of the enzyme are a order of magnitude faster than the rate constants of conformational changes at least. The above results show that the active sites of metal enzyme containing Zn2+ are also situated in a limited and flexible region of the enzyme molecule that is more fragile to denaturants than the protein as a whole.
Amidohydrolases↗
Prevalence of spontaneous otoacoustic emissions in adults revisited.
The potential influence of spectral analysis factors on estimates of the prevalence of spontaneous otoacoustic emissions (SOAE) was explored. The detection of a SOAE was influenced by two spectral factors: (1) the frequency resolution of the spectrum, and (2) the number of spectral averages. For 15 different combinations of these two factors, the estimate of the prevalence of SOAEs for females ranged from 64 to 81% and, for males, from 39 to 55%. Combining across all 15 combinations, 83% of the females and 62% of the males were judged to have SOAEs. These results provide a context for understanding the inconsistencies in previous estimates of the prevalence of SOAEs and underscore the need to employ many different spectral analyses because some SOAEs are only detected when the spectral analyses are suitably tailored.
Adult↗
The incorporation of dietary n-3 polyunsaturated fatty acids into porcine platelet phospholipids and their effects on platelet thromboxane A2 release.
We investigated the dynamic changes in fatty acid (FA) composition in platelet phospholipid (PL) and in the release of thromboxane from stimulated platelets in pigs prefed a diet enriched with polyunsaturated fatty acids (PUFA) of the n-3 and n-6 families of FAs. For 20 days, we fed pigs diets supplemented with either corn oil, fish oil, or fish and borage oil. Platelets were separated from blood drawn at baseline and then on day 4, 8, 12, 16 and 20 of the dietary regimen. Analysis of the FA contained in platelet PL demonstrated that significant changes in PUFA composition occurred during dietary supplementation with fish oil and fish and borage oil. Eicosapentaenoic acid (EPA) from fish oil was rapidly incorporated into PL of platelets and reached a steady-state plateau by day 12. An increase in the content of docosahexaenoic acid (DHA) in the platelets' PL was observed in both groups receiving fish oil. This increase in n-3 PUFA in platelet PL occurred with a concomitant decrease in the content of n-6 FA, primarily of arachidonic acid (AA) in the PL of platelets in both fish oil groups. Dietary supplementation with borage oil, which contains gammalinolenic acid (GLA), increased dihomogammalinolenic acid (DGLA) content in platelet PL. Following A23187 stimulation of platelets, levels of thromboxane B2 (TxB2), the stable metabolite of thromboxane A2 (TxA2), were significantly suppressed in both fish oil groups compared to the corn oil-supplemented group. Dietary supplementation of EPA and EPA plus GLA increased platelet PL content of EPA, and EPA and DGLA, respectively. Following platelet stimulation, TxA2 production was significantly increased, an increase that was attenuated in the platelets from pigs prefed fish oil, and even more so in the fish and borage-oil-prefed pigs.
8,11,14-Eicosatrienoic Acid↗
Effects of the incubation of long-chain polyunsaturated fatty acids on platelet lipids and thromboxane release.
Alterations of dietary lipids have been advocated to manipulate platelet release of thromboxane A2. We studied the effects of incubating platelets with several different polyunsaturated fatty acids on platelet-lipid profile and release of thromboxane A2 in response to platelet stimulation. Porcine platelets were isolated by centrifugation, washed three times in Tyrode's solution, and incubated with fatty acids (500 microM) in Tyrode's solution with albumin. Seven polyunsaturated fatty acids of varying lengths (18-, 20-, and 22-carbon chain) of the omega3 and omega6 families were incubated for 60 min at concentrations of 0, 10, 30, and 100 microM with saturated fatty acids comprising the remainder of the 500 microM fatty acids. The platelets were then stimulated for 5 min with A23187 (30 microM). Indomethacin was added, and the platelets were pelleted. Platelet lipids were extracted in hexane, transesterified and quantified by gas chromatography. Using radioimmunoassay, we measured thromboxane B2, the stable metabolite of thromboxane A2, in the platelets' supernatant. A 1-h incubation in each of the seven polyunsaturated fatty acids had no significant effect on platelet-lipid composition. We found a significant increase in thromboxane B2 production in arachidonic acid (100 microM) incubated platelets (324.0 +/- 63.8% of baseline) that was inhibited by eicosapentaenoic acid (81.0 +/- 26.8%, P < 0.01) and to a lesser extent by dihomogammalinolenic acid (189.8 +/- 28.3%, P < 0.03). We conclude that in altering diets to affect platelet release of thromboxane, the two fatty acids of interest are the 20-carbon chain fatty acids, dihomogammalinolenic acid and eicosapentaenoic acid. The ideal amount of each of these fatty acids to be incorporated entails supraphysiologic but pharmacologically achievable levels of fatty acids in plasma.
Animals↗
Two dominant mutations in the mouse fused gene are the result of transposon insertions.
The mouse Fused locus encodes a protein that has been implicated in the regulation of embryonic axis formation. The protein, which has been named Axin to distinguish it from the product of the unrelated Drosophila melanogaster gene fused, contains regions of similarity to the RGS (regulators of G-protein signaling) family of proteins as well as to dishevelled, a protein that acts downstream of Wingless in D. melanogaster. Loss-of-function mutations at Fused lead to lethality between days 8 and 10 of gestation. Three dominant mutations result in a kinked tail in heterozygotes. Two of the dominant mutations, Fused and Knobbly, result from insertion of intracisternal A particle retrotransposons into the gene. The insertion in Fused, within the sixth intron, creates a gene that produces wild-type transcripts as well as mutant transcripts that initiate at both the authentic promoter and the 3'-most long terminal repeat of the insertion. Knobbly, an insertion of the retrotransposon into exon 7, precludes the production of wild-type protein. Thus the Fused homozygote is viable whereas Knobbly is a recessive embryonic lethal. In both mutants the dominant kink-tailed phenotype is likely to result from the synthesis of similar amino-terminal fragments of Axin protein that would contain the RGS domain, but lack the dishevelled domain.
Animals↗
Localization of plasminogen activator and inhibitor, LH and androgen receptors and inhibin subunits in monkey epididymis.
Epididymis is a site of sperm maturation and storage. Limited and directed-proteolysis regulated by plasminogen activator (PA), plasminogen activator inhibitor type-1 (PAI-1) and other related factors may play an essential role in these processes. Our previous studies have demonstrated that rat epididymis expressed luteinizing hormone receptor (LHR), tissue type (t) and urokinase type (u)PA, mRNAs, and tPA activity was stimulated in vitro by human chorionic gonoadotrophin (HCG). In the present study we further examined localization of mRNAs for tPA, uPA, LHR, androgen receptor (AR), as well as inhibin subunits alpha, betaA and betaB in rhesus monkey epididymis. Using in-situ hybridization with digoxygenin-labelled cRNA probes, we have demonstrated that tPA and PAI-1 mRNAs were localized in epithelial cells of adult monkey epididymis. uPA mRNA was localized in the same areas, but to a much smaller extent. tPA, uPA and PAI-1 mRNAs were greatly expressed in the caput and corpus of adult epididymis than in other regions. In-vitro experiments showed that both tPA and uPA activities in epididymal cells were dramatically stimulated by HCG, but not by follicle stimulating hormone (FSH). LHR (but not FSH receptor) and AR mRNAs were localized in the epithelial cells of the epididymis. However, LHR mRNA was detected in both adult and immature infant monkeys, whereas AR was found only in the adult. Inhibin alpha, betaA and betaB mRNAs were also detected in this organ, betaA mRNA being more strongly expressed in the caput than in other regions of the epididymis. We suggest that LH and androgen may be the key hormones in coordination with the PA-PAI-1 system in regulating epididymal differentiation and sperm maturation.
Androgens↗
Expression of plasminogen activator and inhibitor, urokinase receptor and inhibin subunits in rhesus monkey testes.
The expression and localization of mRNA's for tissue plasminogen activator (tPA), urokinase PA (uPA), uPA receptor (uPAR) and inhibin subunits, alpha, beta A and beta B in monkey testes was investigated. Using in-situ hybridization with digoxigenin-labelled cRNA probes (dig-cRNA), we demonstrated that tPA and plasminogen activator inhibitor type 1 (PAI-1) were expressed in testes of both immature and mature rhesus monkeys. tPA mRNA was localized predominantly in Sertoli cells. Expression level was low in immature testis, increased dramatically in the adult and varied with seminiferous cycle. PAI-1 mRNA was localized mainly in germ cells except late spermatids. uPA mRNA was expressed stage-specifically in Sertoli cells of adult testis. uPA receptor mRNA was localized in germ cells of mature testis but not in spermatogonia or late spermatids. Assayed by fibrin overlay technique, PA activity in conditioned media of purified Sertoli cells (Sc) was negligible, PA activity in media obtained from co-cultured Sertoli and Leydig cells (LS), however, was significantly increased, although Leydig cells alone were not capable of producing any PA activity. Addition of follicle stimulating hormone (FSH) to the incubation medium remarkably increased PA secretion in both Sc and LS cultures. Human chronic gonadotrophin (HCG) had no significant effect on PA activity in the Sc culture but dramatically stimulated PA activity in the co-culture system. Dihydrotestosterone (DHT) did not mimic the effect of HCG. PAI-1 activity was secreted mainly by germ cells and did not differ between the two culture systems. FSH and forskolin inhibited PAI-1 secretion. Inhibin alpha, beta A and beta B subunit mRNAs were localized in Sertoli cells of adult monkey testes, with no obvious difference in the expression levels. These data suggest that PA/PAI-1 and other related factors are expressed in rhesus monkey testis under the control of various hormones, seminiferous cycle and cell-cell interactions through paracrine or autocrine regulation. Locally generated fibrinolysis may play an important role in the process of spermatogenesis.
Animals↗
Different susceptibility of three clinically isolated strains of Cryptococcus neoformans to the fungicidal effects of reactive nitrogen and oxygen intermediates: possible relationships with virulence.
We investigated the susceptibility of three clinically isolated strains of Cryptococcus neoformans with different virulences to reactive nitrogen and oxygen intermediates (RNI and ROI, respectively), representing two important mediators of macrophage microbicidal activity. All mice infected with the highly virulent strain of C. neoformans, YC-11, died within 3 to 6 weeks because of rapid multiplication of the organism in the lungs and dissemination to the brain. In contrast, a weakly virulent strain, YC-13, was almost completely eradicated from the lungs and did not disseminate to the brain, leading to survival of all infected animals during the period of observation (15 weeks). The virulence of the third strain, YC-5, was intermediate between the other two strains. To examine the susceptibility of C. neoformans to the fungicidal effect of nitric oxide (NO) and superoxide anions (O2-), the organisms were exposed to these oxidants, which were chemically generated in a cell-free system. Interestingly, the number of live YC-13 yeast cells was markedly reduced after exposure to NO and O2-. In contrast, YC-11 was almost completely resistant to the killing effect of these oxidants. YC-5 showed an intermediate susceptibility. Our results demonstrate that the resistance of C. neoformans to the fungicidal effects of RNI and ROI is related to virulence, and suggest that the resistance to nitrogen- and oxygen-derived oxidants may be one of the factors to determine the outcome of infection with C. neoformans.
Animals↗