Candida albicans

Mycopathologia, 1988 Jul, 103(1), 29 - 33
Simple method for separating the chlamydoconidia of Candida albicans from its mycelium; Vidotto V et al.; Different physical and chemical methods were used to detach the chlamydoconidia of Candida albicans from its mycelium . The action of concentrated H2SO4 acid for a 4-min period on cultures lysed both the mycelium and the outer but not the inner wall layer of the chlamydoconidia . The sulfuric acid procedure is recommended as the best method to obtain mycelium free chlamydoconidia because of its simplicity, rapidity and low cost.

J Prosthet Dent, 1988 Jul, 60(1), 62 - 70
Model system for the in vitro testing of a synthetic histidine peptide against Candida species grown directly on the denture surface of patients with denture stomatitis; Santarpia RP 3rd et al.; The denture surface provides a nidus for the growth of microbial species that act to initiate, aggravate, and maintain clinical disease . The present investigation describes the development of a model system for the testing of the effectiveness of agents against these microbial species inhabiting the denture surface . It was observed through in vitro growth patterns that the model permitted the testing of representative samples of the microbial flora . Poly-L-histidine was observed to inhibit both Candida albicans and C . glabrata from growing from the denture surface into nutrient broth . Scanning electron microscopy of control and treated denture disks revealed that poly-L-histidine had either eliminated most microbial flora from the denture surface or had effected a noticeable distortion of those Candida blastospores still present on the surface . From microbiologic studies, it appeared that poly-L-histidine had inflicted direct but not lethal damage to the still-attached distorted blastospores because the latter were still able to promote growth in agent-free broth . The antifungal effects of poly-L-histidine were observed to be dependent on the concentration of the polypeptide . The data obtained were consistent for all of the patients regardless of their denture stomatitis classification.

Hautarzt, 1988 Jul, 39(7), 454 - 6
{Hailey-Hailey disease with dissemination and eczema herpeticatum in therapy with etretinate}; Stallmann D et al.; We report a 39-year-old patient with Hailey-Hailey disease localized mainly in the genito-femoral and scrotal areas . During hospital treatment the condition worsened due to superinfection with Candida albicans and gram-negative bacteria . Treatment with systemic steroids followed by aromatic retinoids was tried: eczema herpeticum developed in the affected areas, and dissemination of Hailey-Hailey disease ultimately occurred with papulo-vesicular and histologically characteristic lesions.

Rev Infect Dis, 1988 Jul-Aug, 10 Suppl 2, S419 - 22
Modulation of immune responses by surface polysaccharides of Candida albicans; Domer J et al.; Fungal polysaccharides, especially those from the cell wall of the nonpathogenic yeast Saccharomyces cerevisiae, have been investigated as modulators of immune function for many years . More recently, because surface-associated components are known to be elaborated and circulate during serious episodes of candidiasis, investigators have taken interest in the opportunistic fungus Candida albicans . This review emphasizes the immunomodulatory activities of mannan and cell wall-derived glycoproteins from C . albicans . Mannan extracted with hot citrate buffer has been shown in an antibody-forming cell assay to be a heterogeneous mixture with components capable of enhancing or suppressing antibody responses when administered to mice at or near the time of immunization with type III pneumococcal polysaccharide (SSS-III), a T helper cell-independent antigen, or with sheep erythrocytes (SRBC), a T helper cell-dependent antigen . The components responsible for these opposing effects have been separated on the basis of size or charge by column chromatography . Two similar cell wall glycoproteins, removed from isolated cell walls by different procedures, induced enhancement only of the immune response to SSS-III and SRBC . The mechanism(s) by which these polysaccharides effect modulatory activity has not been elucidated . The enhancing property does not appear related to a direct mitogenic effect on lymphocytes or to stimulation of the production of B cell growth factors or interleukin 2.

J Biol Chem, 1988 Jun 5, 263(16), 7472 - 7
Histatins, a novel family of histidine-rich proteins in human parotid secretion . Isolation, characterization, primary structure, and fungistatic effects on Candida albicans; Oppenheim FG et al.; Histatins 1, 3, and 5 from human parotid secretion were isolated by gel filtration on Bio-Gel P-2 and reverse phase high performance liquid chromatography . The complete amino acid sequences of histatins determined by automated Edman degradation of the proteins, Staphylococcus aureus V8 protease, and tryptic peptides, are as follows: (Sequence: see text) . Histatins 1, 3, and 5 contain 38, 32, and 24 amino acid residues, have molecular weights of 4929, 4063, and 3037, respectively, and contain 7 residues of histidine . Histatin 1 contains 1 mol of phosphate/mol of protein; histatins 3 and 5 lack phosphate . With the exception of Glu (residue 4) and Arg (residue 11) in histatin 1, the first 22 amino acid residues of all three histatins are identical, and the carboxyl-terminal 7 residues of histatins 1 and 3 are also identical . The sequence, -Glu-Phe-Pro-Phe-Tyr-Gly-Asp-Tyr-Gly- (residues 23-29), in histatin 1 is absent in histatin 3; and the sequence, -Gly-Tyr-Arg- (residues 23-25), in histatin 3 is absent in histatin 1 . The complete sequence of histatin 5 is contained within the amino terminal 24 residues of histatin 3 . The structural data suggest that histatins 1 and 3 are derived from different structural genes, whereas histatin 5 is a proteolytic product of histatin 3 . All three histatins exhibit the ability to kill the pathogenic yeast, Candida albicans.

Ann Rheum Dis, 1988 Jun, 47(6), 522 - 5
Intervertebral infection due to Candida albicans in an intravenous heroin abuser; Rowe IF et al.; A 25 year old woman who had received intravenous heroin over one year previously developed an intervertebral abscess due to infection with Candida albicans . Immunological investigation of this patient showed no evidence of a specific defect in the host response to candida.

J Clin Invest, 1988 Jun, 81(6), 1829 - 35
Modulation of the in vitro candidacidal activity of human neutrophil defensins by target cell metabolism and divalent cations; Lehrer RI et al.; We tested the in vitro susceptibility of Candida albicans to three defensins from human neutrophilic granulocytes (HNP-1, 2, and 3), a homologous defensin from rabbit leukocytes (NP-1), and four unrelated cationic peptides . Although the primary amino acid sequences of HNP-1, 2, and 3 are identical except for a single amino-terminal amino acid alteration, HNP-1 and HNP-2 killed C . albicans but HNP-3 did not . C . albicans blastoconidia were protected from HNP-1 when incubations were performed in the absence of oxygen or in the presence of inhibitors that blocked both of its mitochondrial respiratory pathways . Neither anaerobiosis nor mitochondrial inhibitors substantially protected C . albicans exposed to NP-1, poly-L-arginine, poly-L-lysine, or mellitin . Human neutrophilic granulocyte defensin-mediated candidacidal activity was inhibited by both Mg2+ and Ca2+, and was unaffected by Fe2+ . In contrast, Fe2+ inhibited the candidacidal activity of NP-1 and all of the model cationic peptides, whereas Mg2+ inhibited none of them . These data demonstrate that susceptibility of C . albicans to human defensins depends both on the ionic environment and on the metabolic state of the target cell . The latter finding suggests that leukocyte-mediated microbicidal mechanisms may manifest oxygen dependence for reasons unrelated to the production of reactive oxygen intermediates by the leukocyte.

Arthritis Rheum, 1988 Jun, 31(6), 793 - 7
Costochondral involvement in systemic candidiasis in heroin addicts: clinical, scintigraphic, and histologic features in 26 patients; Miro JM et al.; We studied the clinical, scintigraphic, and histopathologic characteristics of 26 intravenous drug abusers with costochondral involvement secondary to systemic infection with Candida albicans . The clinical findings were of a mass appearing in the anterior region of the thorax . In general, signs of inflammation were absent . Histopathologic study of this costochondral mass in 12 patients showed perichondritis in 100% and myositis in 87%, with secondary involvement of cartilage in 43% and of bone in 75% . Results of bone scintigrams using 99mTc-methylene diphosphonate were positive in only 7 of 15 patients (47%), with a correlation between positive uptake and osteitis . Gallium scintigraphy findings were positive in 9 of 10 patients (90%) . The greater sensitivity of 67Ga was probably because the invariably present pericartilaginous inflammatory mass was not always accompanied by secondary cartilage and bone involvement.

APMIS, 1988 Jun, 96(6), 565 - 7
Rapid diagnosis of Pneumocystis carinii using dark-field microscopy on bronchoalveolar lavage . Brief report; Olling S; 20 lavages from patients with pulmonary infiltrates were microscopically studied by a rapid dark field assay and after methenamine silver staining . In 8 samples typical Pneumocystis carinii cysts were identified in the methenamine silver-slides and in 7 of these clusters of round spawn-like particles were also seen in the dark field microscope . One test was "false negative" in the dark field assay due to presence of too few pneumocystes . Another test was "false positive" due to presence of candida albicans spores in the lavage . It is thus possible to give a Pneumocystis carinii diagnosis, with some reservation, within 15 minutes after obtaining the bronchoalveolar lavage.

Mycopathologia, 1988 Jun, 102(3), 157 - 63
Candidal vaginitis in hormone-treated mice: prevention by a chitin extract; Segal E et al.; In view of findings from previous studies that a chitin soluble extract (CSE) blocked adhesion of Candida albicans in vitro and in vivo and prevented thereby a short lived candidal infection in naive mice, we attempted in the present study to block by CSE the development of a persistent infection, induced in hormone-treated animals . Continuous oestrus phase was obtained in mice by repeated weekly subcutaneous injections with estradiol benzoate . Intravaginal inoculation of the hormone-treated mice with 10(7)-10(10) C . albicans cells induced a persistent candidal infection . Fifty three mice were pretreated intravaginally prior to inoculation of C . albicans with 2.5, 5.0 or 10 mg/mouse of a CSE cream and followed up for development of infection in comparison to 30 untreated animals . Twenty four hrs post fungus inoculation the infection rate among the CSE treated mice was 11-23% VS 84% among the controls; the rate increased a week later to 97% among the controls VS 41-50% among the CSE treated . Administering the CSE to the mice prior--and post-yeast inoculation (37 mice), led to increased efficacy of the treatment . The data, indicating that CSE is an effective measure for preventing persistent candidal vaginitis, may open the way to consider a similar approach for prophylaxis of vaginitis in human susceptible populations.

Am J Hosp Pharm, 1988 Jun, 45(6), 1311 - 21
Method for testing the sterility of total nutrient admixtures; Levchuk JW et al.; A test for determining the sterility of a total nutrient admixture (TNA) containing equal quantities of 10% fat emulsion (Liposyn II), 8.5% amino acids injection, and 50% dextrose injection using the USP membrane filtration procedure was developed and evaluated . Membrane filter selection was determined by analysis of flow rates, membrane fluid compatibility, bubble point stability, and rinse fluid requirements . Microbial challenges employing five organisms (Bacillus subtilis, Escherichia coli, Candida albicans, Staphylococcus aureus, and Pseudomonas aeruginosa) and both soybean casein digest and fluid thioglycollate media were used to confirm the ability of the test to detect low-level microbial contamination . A polyvinylidene fluoride membrane was determined to be the most appropriate of the membrane types studied because of its superior flow rate and membrane-fluid compatibility . Bubble point testing revealed no detrimental effects on the membrane . The potential problem of haziness caused by retention of the TNA by the membrane with subsequent release in the culture media (which could result in false-positive growth determinations) was diminished by using a sterile 0.1% peptone solution rinse and careful observation techniques . Performance of the sterility test by six hospital pharmacists required an average of 14.2 minutes . Sterility testing of alternate TNAs compounded with Intralipid and Nutralipid was not feasible because of prolonged filtration times . The basic USP membrane filtration procedure for large-volume injections can be used by hospital pharmacists for testing the sterility of TNAs . When fat emulsions are used in compounding, sterility-testing procedures specific to the emulsion product used should be developed and evaluated.

Eur J Clin Microbiol Infect Dis, 1988 Jun, 7(3), 413 - 4
Antagonism of the direct fungicidal action of miconazole by miconazole fungistasis; Beggs WH et al.; A weakly fungistatic concentration of miconazole in lag phase yeast cultures of Candida albicans antagonized development of phenotypic susceptibility to the direct fungicidal action of high-level (i.e . greater than 10(-5) M) miconazole . After development in the absence of drug, maintenance of susceptibility upon continued incubation was also antagonized by low levels of miconazole . This auto-antagonistic effect has important clinical implications.

J Gen Microbiol, 1988 Jun, 134 ( Pt 6), 1723 - 30
Evidence for a glycosidic linkage between chitin and glucan in the cell wall of Candida albicans; Surarit R et al.; The alkali-insoluble glucan was isolated from regenerating spheroplasts and intact cells of Candida albicans . Sequential enzymic hydrolysis of this fraction by Zymolyase 100T and purified chitinase and subsequent gel filtration produced a fraction which was enriched in glycosaminoglycans . This fraction was analysed by partial acid hydrolysis, TLC and GLC-MS . The GLC-MS peaks identified included 2,3,4,6-tetra-O-methylglucitol acetate and 2,3,4-tri-O-methylglucitol acetate of beta-1,6-glucan and the 3,6-di-O-methyl-2-N-methylglucosaminitol acetate of chitin . In addition, 3-O-methyl-2-N-methylglucosaminitol acetate was identified, which indicated a branch point in chitin . These data provide evidence for a covalent linkage between chitin and beta-(1,6)-glucan through a glycosidic linkage at position 6 of N-acetylglucosamine and position 1 of the glucose in the glucan.

J Gen Microbiol, 1988 Jun, 134 ( Pt 6), 1587 - 95
A complementation analysis by parasexual recombination of Candida albicans morphological mutants; Gil C et al.; Benomyl treatment (at 100 micrograms ml-1) of Candida albicans 1001, and other strains derived from it, determined the appearance of morphological mutants similar to those derived from UV irradiation treatment . A permanent alteration in the morphogenesis of these mutant strains determined their inability to grow by budding, to form oval yeast cells or blastospores (Y-phenotype) and their growth as long filamentous forms, mostly with the appearance of pseudomycelium, giving rise to rough colonies (R phenotype) . In order to carry out a genetic complementation analysis, we isolated morphological mutants that carried other genetic markers (nutritional, conditional lethal) adequate for crosses by means of protoplast fusion . Wild-type hybrids of regular mononuclear oval yeast cells and smooth colonies were obtained by crossing pairs of complementing mutants, whereas hybrids from crosses of non-complementing mutants still retained their morphological alterations . Our results define two complementation groups, which represent two genes relevant for dimorphism, whose alteration interferes with the correct transition from blastospores to mycelium.

Photodermatol, 1988 Jun, 5(3), 133 - 8
Phototoxic properties of quinine and quinidine: two quinoline methanol isomers; Ljunggren B et al.; Clinical photoreactions have been reported for quinine and quinidine after systemic and topical administration . We have investigated the phototoxic properties of these two quinoline methanol isomers in vitro using the Candida albicans inhibition test and photohemolysis, and in vivo with the mouse tail phototoxicity test . Both isomers were phototoxic in the hemolysis model, quinine being the more potent compound . In the Candida test only quinidine was phototoxically active . In the mouse tail model, measuring edema, the phototoxic activity of quinidine was comparatively low, causing a 7.3% wet weight increase of tail tissue at a dose of 150 mg/kg intraperitoneally of drug and 54 J/cm2 of UVA . In spite of its structural similarity to quinidine, quinine was not phototoxic in the mouse . These studies support the assumption, based on clinical data, that quinine photoreactions probably have a non-phototoxic mechanism . For quinidine, however, light-induced reactions based on phototoxicity can not be ruled out, since low-grade phototoxic properties were demonstrated in vivo.

Mycopathologia, 1988 Jun, 102(3), 149 - 56
Variation in adhesion and cell surface hydrophobicity in Candida albicans white and opaque phenotypes; Kennedy MJ et al.; A previous study had established that a select group of pathogenic isolates of Candida albicans was capable of switching heritably, reversibly and at a high frequency (10(-2) to 10(-3)) between two phenotypes ('white' or 'opaque') readily distinguishable by the size, shape, and color of colonies formed on agar at 25 degrees C . This paper describes experiments designed to determine the ability of these two phenotypes to attach to buccal epithelial cells (BECs) and plastic, and to compare the cell surface hydrophobicities of white and opaque phenotypes from three clinical isolates . 'White cells' were found to be significantly more adhesive to BECs, and a strong correlation was also found between phenotype adhesiveness and the percentage of BECs to which C . albicans had attached . The percentage of BECs with one or more attached C . albicans was approximately 90% for the white phenotype and approximately 50% for the opaque phenotype . 'Opaque cells', in contrast, were twice as hydrophobic as white cells, and the percentage of opaque cells bound to BECs by coadhesion was also double that of white cells . The differences in adhesion to plastic between the two phenotypes were not statistically significant and there was no distinct trend to suggest which phenotype might be more adhesive to plastic . These results indicate that several factors are involved in the adhesion of C . albicans to plastic, and confirm the hypothesis that cell surface hydrophobicity is of minor importance in direct adhesion to epithelial cells but that it may contribute to indirect attachment to epithelial cells by promoting yeast coadhesion.(ABSTRACT TRUNCATED AT 250 WORDS)

Lipids, 1988 Jun, 23(6), 534 - 8
Geraniol interferes with membrane functions in strains of Candida and Saccharomyces; Bard M et al.; Geraniol, an olefinic terpene, was found to inhibit growth of Candida albicans and Saccharomyces cerevisiae strains . Geraniol was shown to enhance the rate of potassium leakage out of whole cells and also was shown by fluorescence polarization to increase C . albicans membrane fluidity . Biophysical studies using differential scanning calorimetry, fluorescence polarization and osmotic swelling of phospholipid vesicles demonstrated that geraniol decreased the phase-transition temperature of dipalmitoylphosphatidylcholine vesicles, affected fluidity throughout the bilayer, particularly the central portion of the bilayers, and caused an increase in bilayer permeability to erythritol . Geraniol may have potential use as an antifungal agent.

J Med Vet Mycol, 1988 Jun, 26(3), 199 - 202
Epidemiology of an outbreak of Candida endophthalmitis in heroin addicts: identification of possible source of infection by biotyping; Shankland GS et al.; Biotyping was employed to investigate possible sources of Candida endophthalmitis in heroin addicts . Isolates of Candida albicans recovered from patients and from injection paraphernalia, including lemon juice diluent from lemon-shaped plastic containers, were biotyped . The predominant biotypes were 153, 15 3/7 . Similar biotypes were recovered from lemon, mouthwash, mouth swab and vitreous samples.

J Med Vet Mycol, 1988 Jun, 26(3), 173 - 85
Morphological aspects of gastrointestinal tract invasion by Candida albicans in the infant mouse; Cole GT et al.; The infant mouse has proved to be a useful model for examination of various aspects of gastrointestinal and systemic candidosis . Oral-intragastric inoculation of 5-6-day-old mice with yeast of a virulent strain of Candida albicans (CA30) resulted in systemic spread within 30 min after challenge . Histological examinations of the gastrointestinal (GI) tract have shown that the highest frequency of invasion of the mucosa by yeast cells occurred in the region of the jejunum 1-3 h after inoculation . Results of ultrastructural examinations of sites where the fungus invaded the bowel wall suggested that C . albicans yeast cells are capable of progressive extracellular digestion of the intestinal mucus barrier and microvillus layer, followed by intracellular invasion of columnar epithelial cells . Minimal disruption of cytoplasmic contents of the host epithelial cells appears to result from invasion and transmigration of the pathogen . The infant mouse model is suggested to be well suited for localization of extracellular products of C . albicans yeast in vivo which may play pivotal roles in the invasion of host tissue during GI candidosis.

J Antimicrob Chemother, 1988 Jun, 21(6), 755 - 63
Inhibition of adherence of Candida albicans by conventional and experimental antifungal drugs; Vuddhakul V et al.; We tested the effects of antifungal drugs on adherence of Candida albicans in vitro . Significant reduction of adherence occurred after 2 h incubation with amphotericin B, nystatin, miconazole, econazole, ketoconazole, chlorohexidine and ICI 195,739 . Significant inhibition of candida adherence by 5-fluorocytosine and amorolfin required 18 h incubation . Combinations of amphotericin B with 5-fluorocytosine, miconazole, ICI 195,739 and amorolfin resulted in synergistic inhibition of adherence . Adherence is an important pathogenic mechanism in candida infections and interference with this process may represent a major component of the mode of action of antifungal drugs.

J Immunol, 1988 Jun 1, 140(11), 3893 - 9
A novel natural inhibitor from Candida albicans hyphae causing dissociation of the neutrophil respiratory burst response to chemotactic peptides from other post-activation events; Smail EH et al.; Previous work established that Candida albicans hyphae release several inhibitors of human neutrophil function . We now report that the crude hyphal inhibitory product (CHIP) inhibits superoxide anion (O2-) production stimulated by FMLP in a dose-related manner with an EC50 of approximately 2 micrograms/ml . CHIP also inhibited O2- production stimulated by A23187 and by opsonized zymosan, although this effect could be overcome by increasing the concentration of agonist . No inhibition of the PMA-stimulated burst was seen at any concentration of PMA tested, indicating that CHIP neither affected polymorphonuclear neutrophil viability nor quenched superoxide anion detection . A saturating dose of inhibitor had no effect on chemotaxis stimulated either by 0.1 to 100 nM FMLP or by zymosan-activated serum . Peak inositol trisphosphate levels stimulated by FMLP were not inhibited by a dose of CHIP producing maximum inhibition of FMLP-induced superoxide production . Peak changes in cytosolic free calcium levels (as measured by indo-1 fluorescence) stimulated by 50 nM or greater FMLP were unaffected by CHIP, although for subsaturating doses of FMLP a more rapid decline from peak calcium levels was seen in CHIP-exposed cells . Taken together, these data suggest that the common fungal pathogen C . albicans releases a substance that selectively impairs the neutrophil respiratory burst . It appears to do so without inhibiting the fully assembled NADPH oxidase and with minimal or no effect on events tightly coupled to FMLP-R/G protein activation, suggesting that these events may be uncoupled from activation of the burst . In addition, the absence of effect of CHIP on chemotaxis despite profound inhibition of the respiratory burst suggests these neutrophil functions may be mediated by divergent transduction pathways.

Pediatrics, 1988 Jun, 81(6), 785 - 8
Bronchoalveolar lavage for diagnosis of pneumonia in the immunocompromised child; Frankel LR et al.; Seven children with immunocompromised states were referred to the pediatric bronchoscopy service for evaluation of pneumonia . Flexible fiberoptic bronchoscopy accompanied with bronchoalveolar lavage was performed in all seven of these children . A definitive diagnosis was made for six of these seven patients . The diagnosis included Pneumocystis carinii in three, Candida albicans in two, and cytomegalovirus in one . There were no complications associated with the procedure . Flexible fiberoptic bronchoscopy with bronchoalveolar lavage should be considered early in the evaluation of the immunocompromised child with pneumonia.

Arch Fr Pediatr, 1988 May, 45(5), 341 - 2
{Anuria in an infant caused by an intrapyelic mycelial bezoar in a solitary kidney}; Burguet A et al.; A 4 month-old premature infant having received prolonged intensive care for necrotizing enterocolitis and Pseudomonas infection, developed anuria with intrapyelic fungus ball developed in a congenital single kidney . Review of the literature found 19 similar cases and emphasized the difficulty of an early diagnosis and the usefulness of renal ultrasonography for its detection . Moreover the opportunity to treat premature neonates carrying candida albicans with IV amphotericin B and flucytosine before the occurrence of an uneasy treatable urological obstacle in discussed.

Am J Hosp Pharm, 1988 May, 45(5), 1089 - 91
Viability of microorganisms in fluorouracil and cisplatin small-volume injections; Holmes CJ et al.; The ability of various microorganisms to survive in cisplatin injection or fluorouracil injection in small-volume containers was assessed . Inoculum suspensions of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Pseudomonas cepacia, Candida albicans, or Aspergillus niger were injected into polyvinyl chloride minibags containing 20 mL of either fluorouracil injection 50 mg/mL or cisplatin injection 1 mg/mL in 0.9% sodium chloride injection . All minibags were stored at 25 degrees C for 28 days . Three minibags containing only the sodium chloride solution and 18 minibags containing the sodium chloride solution inoculated with microorganisms served as negative and positive controls, respectively . Samples (1 mL) were obtained within 30 minutes of inoculation and again on days 1, 2, 4, 7, 14, 21, and 28 . All microbial species lost viability in both the cisplatin and the fluorouracil admixtures over the study period . In most instances, this loss was more pronounced than that in the positive control solution . Whether the pH of the solutions contributed to this loss of viability was not determined . Under the conditions of this study, admixtures containing cisplatin and fluorouracil did not support rapid growth of microorganisms when stored at room temperature for up to 28 days.

J Antimicrob Chemother, 1988 May, 21(5), 633 - 5
Pharmacokinetic study of the interaction between rifampicin and ketoconazole; Doble N et al.; This study assessed the potential pharmacokinetic interaction between rifampicin and ketoconazole, two drugs used to treat the increasingly common combination of Mycobacterium tuberculosis and Candida albicans infection in AIDS patients . The peak plasma rifampicin concentrations in six healthy male subjects were not altered when taken in conjunction with ketoconazole . However, the peak plasma ketoconazole levels were significantly diminished when taken in conjunction with rifampicin, compared to when taken alone (P less than 0.015) . The mean area under the curve (AUC) for ketoconazole was significantly diminished when taken with oral or intravenous rifampicin (P less than 0.001).

Antimicrob Agents Chemother, 1988 May, 32(5), 702 - 5
Role of cell defense against oxidative damage in the resistance of Candida albicans to the killing effect of amphotericin B; Sokol-Anderson M et al.; A laboratory-derived mutant of Candida albicans B311 (L) and a clinical isolate (C) of C . albicans, both lacking membrane ergosterol, were less susceptible to amphotericin B (AmB)-induced cell membrane permeability to K+ and lethality than was the wild-type laboratory strain (B311) which contained ergosterol . The resistance of L and C to AmB-induced killing was much greater than the level of resistance to AmB-induced cell membrane permeability . L and C were also less susceptible to killing by H2O2 than was B311, and when treated with menadione, they each produced less H2O2 than did B311 . In addition, their levels of catalase activity were 3.8-fold (L) and 2-fold (C) higher than that of B311 . The ergosterol deficiency in L and C probably impaired AmB binding to the cells, thereby lowering AmB effectiveness as measured by both cell membrane permeability and killing . Resistance of strains L and C to oxidation-dependent damage likely contributed to a diminished response to AmB-induced lethality.

Ann Rheum Dis, 1988 May, 47(5), 359 - 63
Reduction of the surface charge of blood polymorphonuclear cells by rheumatoid sera and heat induced aggregated human IgG (HAGG); Brown KA et al.; Cell electrophoresis identifies two main subpopulations of blood polymorphonuclear cells (PMNs), which in terms of the speed of their anodic migration are referred to as the fast and slow population . When blood PMNs from normal healthy subjects were incubated in medium containing 20% RA serum there was a decrease in the percentage of fast cells with a corresponding increase in the slow population that was directly related to the levels of circulating immune complexes present in the sera . Similar results were obtained when using heat induced aggregated human IgG (HAGG) or Candida albicans instead of RA serum . The 'slowing' effect of HAGG, which was transient and time dependent, appeared to be due to its internalisation by the PMNs . These results suggest that in RA the large number of blood PMNs with a low surface charge (i.e., the slow population) may arise as a result of the constant interaction of these cells with circulating immune complexes.

J Reprod Med, 1988 May, 33(5), 421 - 2
Microwave sterilization of Candida on underwear fabric . A preliminary report; Friedrich EG Jr et al.; Candida-contaminated underwear might not be sterilized by ordinary laundering . The effectiveness of microwaving against Candida albicans on fabric was therefore determined . Swatches of Candida-impregnated cotton underpants fabric were subjected to domestic microwaving at the high setting for up to 30 minutes . If the fabric was microwaved dry, the Candida organisms survived . If the fabric was moistened, sterilization occurred within five minutes . Microwaving wet, freshly laundered cotton underpants should sterilize residual Candida and reduce the risk of reinfection.

J Clin Microbiol, 1988 May, 26(5), 842 - 5
Variation of electrophoretic karyotypes among clinical isolates of Candida albicans; Merz WG et al.; Orthogonal-field-alternation gel electrophoresis was used to compare clinical isolates of Candida albicans by resolving chromosome-sized DNA molecules into an electrophoretic karyotype . Seven to nine bands were observed among isolates recovered from 17 patients . In addition, 14 distinct electrophoretic patterns were noted among the isolates from these patients . In a given individual, isolates were likely to have identical electrophoretic patterns . Therefore, the electrophoretic karyotype patterns demonstrated by orthogonal-field-alternation gel electrophoresis can be used to designate a strain for epidemiologic studies.

J Surg Res, 1988 May, 44(5), 479 - 92
Candida albicans translocation across the gut mucosa following burn injury; Inoue S et al.; Normal guinea pigs were challenged intragastrically with Candida albicans 1 hr prior to a 30 or 50% flame burn to determine if burn injury increased translocation of the yeasts across gut mucosa . Tissues were harvested between 3 and 24 hr postburn and cultured on Sabouraud dextrose agar . Control animals (no yeast challenge) showed no yeast in intestinal homogenates or in the mesenteric lymph nodes (MLN) . At a dose of 1 X 10(9) yeasts, they did not escape from the gut lumen, with either a 30 or 50% burn . At a dose of 2 to 4 X 10(10) organisms, they translocated to the MLN in 92% of the 50%-burned animals (P less than 0.001), 75% of the 30%-burned animals (P less than 0.05), and 12.5% of unburned animals . The ileal mucosa appeared to be the most susceptible site for yeast invasion . To observe the penetration through the gut mucosa and/or translocation to other tissues, yeasts were labeled with biotin before administration, and tissues were stained with avidin-peroxidase diaminobenzidine sequence . With biotinylated yeasts, phagocytized organisms were observed in large numbers in the lamina propria and mesenteric lymph nodes but they were not viable upon culture . Toluidine blue staining of semithin sections revealed that translocated yeasts were located selectively in the lymphoid follicles of the MLN, entrapped by macrophages.

J Infect Dis, 1988 May, 157(5), 950 - 8
Intragastric colonization of infant mice with Candida albicans induces systemic immunity demonstrable upon challenge as adults; Domer JE; A murine model of long-term colonization with Candida albicans, established by intubating infant CBA/J mice, was used to study the effects of colonization on the development of Candida-specific immune responses in mature animals . Two striking consequences were stimulation of protective immune responses, as evidenced by increased survival and decreased numbers of colony-forming units in mice challenged intravenously (iv), and priming of the T cell component responsible for delayed hypersensitivity (DH) . Colonized mice, tested as adults by using a cell wall-derived antigen, had little or no demonstrable DH . If inoculated once cutaneously with viable Candida, however, they responded with significantly enhanced DH reactions that could not be correlated with the cutaneous inoculation . Inoculation of the same number of dead organisms into infant mice neither primed animals for enhanced DH nor stimulated protective immunity . Antibody to cytoplasmic antigens of Candida was demonstrable in colonized animals, and its production was increased significantly in animals challenged iv with the highest dose of blastoconidia.

Infect Immun, 1988 May, 56(5), 1388 - 90
Comparison of the extracellular proteinase activity produced by a low-virulence mutant of Candida albicans and its wild-type parent; Edison AM et al.; The production of extracellular proteinase by MY1049, a low-virulence mutant of Candida albicans, was compared with that of its wild-type parent, MY1044 . Both strains were grown in a medium containing bovine serum albumin as a nitrogen source to induce proteinase production . Under these conditions, the proteinase activity per cell in the MY1049 cultures was the same as or higher than that of MY1044 cultures . However, MY1049 grew much more slowly than MY1044, and the total proteinase activity of the MY1049 culture remained well below that of the MY1044 culture . In a minimal medium with ammonium sulfate as the nitrogen source, MY1049 grew as rapidly as did MY1044 . No significant differences were observed in the effects of inhibitors produced by MY1049 and MY1044 . Our previous work indicated that MY1049 was able to grow and produce abundant mycelium in the renal calices of infected mice but that the strain was unable to invasively colonize the renal tissue . The decreased ability of MY1049 to grow in a protein-rich environment, despite its ability to produce extracellular proteinase, may enable the host to contain the mutant strain before the fungal cells invade the tissue.

Am J Reprod Immunol Microbiol, 1988 May, 17(1), 14 - 7
Bacteriology of the cervix in cases of infertility: effect on human and animal spermatozoa and role of elastase; Kaur M et al.; Microorganisms such as Bacillus subtilis, Pseudomonas aeruginosa, Escherichia coli, and Candida albicans isolated from cervices of infertile human females inhibited motility and agglutinated human, cow bull, buffalo bull, and rat spermatozoa in vitro . Fifty percent of the infertile females studied carried elastase-positive microorganisms . Cell-free culture supernatants of 72-hr-old elastase-positive cultures were spermicidal within 60 min of contact with sperm, while elastase-negative cultures were spermicidal in 4-6 hr . Cultures of all the cervical isolates were spermicidal and agglutinated human, cow bull, buffalo bull, and rat spermatozoa, and these activities increased with age of the culture . Human sperm showed only tail-to-tail agglutination, while cow bull, buffalo bull, and rat spermatozoa showed mainly head-to-head agglutination . Spermicidal activity was also attributable to elastase, which was present more in 72-hr-old cultures than in 24-hr-old cultures.

J Clin Microbiol, 1988 May, 26(5), 890 - 2
Reaction of Bacillus subtilis products with amebocyte lysates of the Japanese horseshoe crab, Tachypleus tridentatus; Hodes DS et al.; Autoclaved aqueous extracts of Candida albicans cells (and the glucans isolated from them) give a positive reaction with a chromogenic substrate combined with amebocyte lysates of the Japanese horseshoe crab, Tachypleus tridentatus (CS-TAL) . The extracts and glucans activate the lysate enzyme compound G, which in turn activates clotting enzyme . Activated clotting enzyme causes a positive CS-TAL reaction . C . albicans extracts and glucans react positively with a commercially available, unaltered CS-TAL preparation (Toxicolor), but they give a negative reaction with a CS-TAL from which compound G has been excluded (Endospecy) . An autoclaved, sterile preparation of Sabouraud glucose broth used as a control in one experiment gave (like Candida extracts) a positive reaction with Toxicolor and a negative reaction with Endospecy . We found that the peptone powder used to make the Sabouraud glucose broth was contaminated with a strain of Bacillus subtilis . Autoclaved aqueous extracts of culture-grown B . subtilis cells were positive with Toxicolor and negative with Endospecy . This was also the case with two other strains of B . subtilis . Polysaccharides obtained from these extracts gave the same result . Endotoxin activates clotting enzyme through activation of the lysate enzyme compound C, which is present in both Toxicolor and Endospecy . Endotoxin, therefore, reacts with both CS-TAL preparations . Simultaneous assay with Toxicolor and Endospecy distinguishes endotoxin from fungal products, but since products of fungi and B . subtilis both give a positive Toxicolor and a negative Endospecy test, a simultaneous assay cannot differentiate them . However, this does not decrease the clinical value of the simultaneous Toxicolor-Endospecy assay for distinguishing fungal infection from endotoxemia because B . subtilis so rarely causes disease that it can be excluded from clinical consideration.

J Cell Biol, 1988 May, 106(5), 1765 - 72
Antibodies to the conserved cytoplasmic domain of the integrin beta 1 subunit react with proteins in vertebrates, invertebrates, and fungi; Marcantonio EE et al.; The integrin family of cell surface receptors can be divided into three groups on the basis of their homologous beta subunits: beta 1, beta 2, and beta 3 . We have raised an antibody against a synthetic peptide corresponding to the COOH-terminal domain of the chicken integrin beta 1 subunit that reacts with beta subunits from a variety of vertebrates, invertebrates, and fungi, demonstrating strong evolutionary conservation of sequences in this domain . In Drosophila cells, the antibody recognizes integrin alpha beta complexes that appear to be identical with position-specific antigens . Cross-reactive proteins are also detected in Caenorhabditis elegans and Candida albicans . The antiserum is specific for beta 1 subunits and does not recognize other integrin beta subunits in humans . In immunofluorescence analyses of cultured cells, the antibody reacts only with permeabilized cells confirming that this highly conserved COOH-terminal segment is a cytoplasmic domain.

J Gen Microbiol, 1988 May, 134 ( Pt 5), 1375 - 84
Ethanol tolerance and the induction of stress proteins by ethanol in Candida albicans; Zeuthen ML et al.; Ethanol is one of the products of the metabolism of glucose by Candida albicans . The amount produced is directly related to the concentration of glucose in the medium . The fungus utilizes ethanol as a sole source of carbon but is relatively intolerant of ethanol in its environment . Ethanol induces germ tube formation by blastoconidia of C . albicans . Germination was not seen under fermentation conditions even though the amount of ethanol produced was in the range form stress proteins that are similar to heat shock proteins . The possibility that stress proteins may regulate germ tube formation by C . albicans is discussed.

J Gen Microbiol, 1988 May, 134 ( Pt 5), 1265 - 74
Cell wall components of Candida albicans as immunomodulators: induction of natural killer and macrophage-mediated peritoneal cell cytotoxicity in mice by mannoprotein and glucan fractions; Scaringi L et al.; Cell wall components from Candida albicans were compared to intact cells for their ability to induce natural cytotoxic immunoeffectors in the peritoneal cavity of mice . A soluble mannoprotein extract (MP) and an insoluble glucan fraction (GG) strongly stimulated the generation of peritoneal effectors capable of lysing YAC-1 and P-815 tumour cell lines in vitro . The anti-YAC-1 effectors were characterized as natural killer (NK) lymphocytes while the anti-P-815 effectors appeared to be activated macrophages . The activity of each fraction was typically dose-dependent and both fractions differed from whole cells in the kinetics of induction of cytotoxicity . However, the NK and macrophage effectors generated by these materials had similar functional and phenotypic properties, irrespective of the material used as inducer . No mannoprotein was detected in the insoluble glucan fraction GG . Hence, the immunoenhancing activity of GG could not be attributed to the presence of some MP or MP-like component . Mannan-rich fractions with low (less than 3%) protein content (M) or extracted by hot alkaline reagent (M-alk) were inactive as NK and macrophage inducers . Thus, the cell wall of C . albicans contains at least two distinct macromolecular complexes which mediate the induction in murine peritoneal exudates of cytotoxic effectors active against tumour cell lines.

J Gen Microbiol, 1988 May, 134 ( Pt 5), 1079 - 87
Cytoplasmic alkalinization during germ tube formation in Candida albicans; Stewart E et al.; Weak acids were used to measure the internal pH of yeast cells of Candida albicans that had been induced to form buds or germ tubes . Under conditions that supported germ tube formation the internal pH rose from around 6.8 to over 8.0 after 30 min in two different induction media . Internal pH measured by 31P NMR confirmed this pattern and also showed that the internal pH fell to around 7.0 prior to the outgrowth of germ tubes . Conditions which led to budding induced less cytoplasmic alkalinization . This alkalinization was brought about when cells were inoculated into media of neutral pH and at an increased temperature . Increasing the temperature of the medium augmented the alkalinization of the cytoplasm induced by raising the external pH . Strains of C . albicans defective in the ability to produce germ tubes did not show this dramatic cytoplasmic alkalinization under conditions which normally supported filamentous growth . The raising of internal pH may be due to the activation of the plasma membrane proton-pumping ATPase since diethylstilboestrol inhibited the cytoplasmic alkalinization and germ tube formation without causing irreversible loss of cell viability . The results show that the induction of the dimorphic transition in this organism is accompanied by a steep rise in internal pH . It is not known whether these changes are the cause or consequence of morphogenesis.

Pediatr Dermatol, 1988 May, 5(2), 83 - 7
Effects of diaper types on diaper dermatitis associated with diarrhea and antibiotic use in children in day-care centers; Campbell RL et al.; Infants and toddlers in day-care centers have a relatively high frequency of diarrhea and/or oral antibiotic use, and may be at increased risk of developing diaper dermatitis when diapered . A six-month, prospective, double-blind study was conducted in day-care centers in Houston, Texas, to determine the frequency of diarrhea, antibiotic use, and diaper dermatitis in infants and toddlers wearing conventional (cellulose-only core) disposable diapers or disposable diapers with a core of absorbent gelling material (AGM) and cellulose . A questionnaire was administered weekly to the day-care staff to gather health information, and weekly visual examinations were made of children for diaper dermatitis . The frequency of diarrhea was 1.9 episodes per child-year and that of antibiotic use was 3.3 courses per child-year . Infants diapered in disposable diapers with AGM had a significantly (P 0.032) lower mean grade of diaper dermatitis during diarrhea episodes and a lower (P 0.054) mean grade during antibiotic use, compared to those diapered in conventional disposable diapers . There was no significant difference between groups with regard to isolation of Staphylococcus aureus or Candida albicans from superficial skin cultures of the diapered area . The results indicate that diarrhea and antibiotic use occur frequently in children in day-care centers, and that the severity of diaper dermatitis is less in children wearing AGM disposable diapers than those wearing conventional disposable diapers in that setting.

Zentralbl Bakteriol Mikrobiol Hyg {A}, 1988 May, 268(3), 405 - 15
Renal pathology and spleen cell chemiluminescence of mice infected with a wild-type and a low-virulence mutant of Candida albicans; Fromtling RA et al.; Pathogenicity and virulence factors were studied for a wild-type strain of Candida albicans (MY 1044) and an auxotrophic, temperature-sensitive mutant strain (MY 1049) that was derived by ultraviolet irradiation . The mutant was a temperature-sensitive, serine auxotroph . Renal pathology and chemiluminescence of spleen cells from infected mice were assessed in an attempt to identify virulence factors . Renal damage was evident following intravenous infection with either strain, although the mutant appeared to be less invasive; MY 1044 produced characteristic miliary, subcapsular lesions, while the mutant (MY 1049) produced large granulomas . Spleen cells from each infected group were stimulated in vitro with either phytohemagglutinin, concanavalin A or opsonized yeast cells to measure the respiratory burst using a luminol-dependent chemiluminescence assay . The highest chemiluminescence responses correlated with severe renal damage (uremia) and not with yeast virulence . No differences in chemiluminescence were observed among spleen cells from mice infected with either strain when renal pathology was minimal.

Pathol Biol (Paris), 1988 May, 36(5), 575 - 80
{Comparative action of 8 azole derivatives against Candida albicans: fungistatic action and cytologic study by scanning electron microscopy}; Mallie M et al.; The authors compared the in vitro antifungal activity of eight imidazole derivatives (clotrimazole, econazole, isoconazole, ketoconazole, miconazole, oxiconazole, terconazole, tioconazole) against 42 strains of Candida albicans by the agar dilution method using casitone medium . The geometric (G) mean MIC values, the MIC 90 and the MIC 50 values and the corresponding standard deviations of each antifungal agent were determined . The G-MIC values were found to be in the range of 0.008-0.390 micrograms ml-1 . The effects of these eight antifungal agents on the ultrastructure of C . albicans yeast cells and spheroplasts were studied by scanning electron microscopy (SEM) . The results showed a good correlation between the lesions observed and the structure of the imidazole derivatives tested . On the basis of the SEM results, the compounds could be divided into three groups: (1) ketoconazole and terconazole; (2) econazole, isoconazole, miconazole, oxiconazole and tioconazole; (3) clotrimazole.

Mycopathologia, 1988 May, 102(2), 115 - 21
Effect of Candida albicans cell wall components on the adhesion of the fungus to human and murine vaginal mucosa; Lehrer N et al.; In this study, cell walls from Candida albicans were separated and chitin was isolated from these cell walls . A chitin soluble extract (CSE) prepared from the chitin inhibited in vitro adhesion of C . albicans to human epithelial vaginal cells (VEC), and blocked in vivo attachment to murine vaginal mucosa, thereby preventing candidal infection in these animals . These findings suggest that the CSE acts as an adhesin-like substance . Fractionation of CSE yielded two fractions: FI and FII, of which only FI exhibited inhibitory activity . Chemical analysis of CSE and its two fractions revealed that CSE contains over 70% of proteins, most of which were found in the non-active fraction . In addition, 3% of amino-sugars were found in the FI active fraction . Lipids were also detected in the unfractionated CSE and in both fractions . Experiments to further characterize the component(s) in the CSE inhibiting the attachment of C . albicans are in progress in our laboratory.

Eur J Immunol, 1988 May, 18(5), 697 - 703
Liver-associated macrophage precursor cells proliferate under impairment of regular hemopoiesis; Decker T et al.; We reported previously that immature macrophage precursor cells can be isolated from spleen and liver of cyclophosphamide or pyran copolymer-pretreated mice . We now extended our investigations to livers of normal, untreated specific pathogen-free mice . Using the response to the macrophage growth factor colony-stimulating factor-1 (CSF-1) and the presence of the mouse macrophage-specific F4/80 antigen as criteria of definition, in the liver of normal mice we could demonstrate macrophage precursor (M phi P) cells by means of proliferation assays and flow cytometric analysis . The amount of M phi P present in the normal liver was significantly increased after administration of pyran copolymer . Also an enhanced proliferative response to CSF-1 as well as augmented natural killer activity and cytostasis of Candida albicans was noted in liver nonparenychymal cells (LNPC) after treatment of bone marrow (BM)-irradiated, splenectomized mice with pyran copolymer . Since the irradiated BM was actually proven to be silent by assessment of BM number and proliferative capacity and by scoring white blood cells, our findings suggest a response of endogenous liver M phi P under the applied conditions . Further evidence for the presence of endogenous liver hemopoietic cells was obtained from transplantation experiments in which LNPC brought about the survival of lethally irradiated mice . The data point towards a significance of the liver in disposing hemopoietic cells to the organism under impairment of regular hemopoiesis.

Klin Monatsbl Augenheilkd, 1988 Apr, 192(4), 348 - 53
{The so-called "ocular histoplasmosis syndrome"}; Behrens-Baumann W et al.; The authors describe seven patients presenting with ophthalmoscopic findings typical of "presumed ocular histoplasmosis syndrome." However, no humoral antibodies could be demonstrated . Moreover, the results of skin tests were all negative even after "boostering." Hence, the diagnosis of ocular histoplasmosis had to be ruled out . Tests for listeriosis, lues, leptospirosis, ornithosis, Toxocara canis, toxoplasmosis, Larva migrans, and Candida albicans were also negative . There are evidently other, so far unknown, agents which lead to an ophthalmoscopic picture that mimics ocular histoplasmosis with its typical "punched-out lesions" and central hemorrhagic chorioretinopathy . One of these agents may be Epstein-Barr virus, because two of six patients had increased antibody levels of Epstein-Barr nuclear antigen and early antigen, indicating an active or persistent state of viral infection.

Br J Obstet Gynaecol, 1988 Apr, 95(4), 408 - 10
Candidiasis in women fitted with an intrauterine contraceptive device; Parewijck W et al.; Vaginal colonization by Candida spp . was compared in 117 women fitted with an intrauterine contraceptive device (IUCD users) and in 100 women not wearing an IUCD (control group) . None of the subjects had factors currently assumed to predispose to yeast colonization or infection . Yeasts were present significantly more often in the IUCD users (20%) than in the control group (6%) . In two of the 21 women with positive cultures the tail of the IUCD yielded substantially more colonies than the vaginal specimen and in seven, only the tail culture was positive . These findings strongly suggest that the IUCD is a predisposing factor in vaginal colonization by Candida strains . In half the women the presence of yeasts in the vagina was not associated with signs and symptoms of clinical infection . Of the 29 yeast strains isolated 17 were C . albicans, there was no difference in the prevalence of C . albicans between IUCD users and non-users or between symptomatic and asymptomatic womenPIP: 217 women were investigated for the presence of genital candidiasis . 117 women had an IUD; the other 100 women did not . 23 IUD wearers and 6 of the non-wearers were found to harbor Candida in the vagina . 50% of the IUD wearers and 66% of the yeast-positive controls were asymptomatic . Pieces of IUD tails were snipped and cultured from 21 of the IUD wearers, and in 7 of them only the IUD tails yielded cultures . 59% of the yeasts were identified as Candida albicans and the rest as other strains of Candida . This study confirms the hypothesis that IUD use predisposes to colonization and infection by Candida albicans and other strains . The fact that the yeast organisms were more prevalent on the IUD tails than in the vaginal mucosa indicates that the IUD tail acts as a reservoir of infection .

J Ethnopharmacol, 1988 Apr, 22(3), 307 - 13
Anticandidal activity of plants used for the treatment of vaginitis in Guatemala and clinical trial of a Solanum nigrescens preparation; Giron LM et al.; An ethnobotanical survey detected 71 plants used for the treatment of vaginitis by traditional healers, health promoters and midwives . Extracts prepared by maceration of plants in 50% methanol were impregnated on absorbent paper disks and placed over plates with Candida albicans . Eight (11.3%) of these plants showed some degree of inhibition . Solanum nigrescens was chosen for further studies . A cream containing a 50% ethanolic maceration was applied daily to the vagina of female guinea pigs for 15 days and observed for another 15 days . Since no inflammatory changes were observed, this preparation was used for clinical trials . Two groups of 50 non-pregnant women with confirmed C . albicans vaginitis were treated for 15 days, one group with intra-vaginal suppositories containing S . nigrescens maceration and the other with nystatin suppositories . By statistical analysis it was demonstrated that both groups behaved in a similar beneficial way suggesting that this plant may be effective for the treatment of candidal vaginitis.

Allergy, 1988 Apr, 43(3), 201 - 5
Relationship of immediate and delayed hypersensitivity to nasopharyngeal and intestinal growth of Candida albicans in allergic subjects; Koivikko A et al.; The growth of C . albicans yeast in the nasopharynx and in the anus as well as allergy symptoms were followed up for 8 months in 67 patients with bronchial asthma, allergic rhinitis and/or atopic eczema . 38 of the patients were skin prick test positive and 29 negative to C . albicans allergen extract . 32 of the patients had positive and 19 negative delayed skin reactions . The nasal, bronchial and skin symptoms of the yeast-sensitive allergic patients were not associated with the nasopharyngeal nor anal occurrence of C . albicans or other yeasts . The use of nasal or inhaled steroids had no effect on the occurrence of Candida in the nasopharynx . It was observed that immediate skin sensitivity had a positive correlation and the delayed sensitivity a negative correlation with the occurrence of C . albicans growth in nasopharynx and anus . These findings are in agreement with the concept that impaired cell-mediated immunity to C . albicans may lead to increased IgE response . This may explain the increased liability towards C . albicans nasopharyngeal and gastrointestinal "saprophytic" growth.

Am J Obstet Gynecol, 1988 Apr, 158(4), 997 - 1001
High-frequency switching in Candida albicans and its relations to vaginal candidiasis; Soll DR; Candida albicans possesses the ability to switch reversibly and at high frequency between a number of heritable phenotypes distinguishable by colony morphology and in some cases cellular phenotype . In the original switching system identified in C . albicans, it was demonstrated that cells could switch at frequencies as high as 10(-2) among seven distinct colony phenotypes including smooth, star, ring, stipple, irregular wrinkle, hat, and fuzzy . In a second switching system first discovered in a systemic infection, cells switched at high frequency between a white and an opaque colony former . Recently, switching was discovered in isolates from patients with vaginal candidiasis and multiple switch phenotypes were cloned from an individual vagina . Switching may contribute to the pathogenesis of C . albicans by providing it with the capacity to invade diverse sites in the body, to change resistance to antifungal agents, or to change antigenicity . The molecular basis of switching is probably due to the reversible transposition or rearrangement of genomic elements, although a direct correlation between recently identified genomic rearrangements and phenotypic switching has not been made.

Am J Obstet Gynecol, 1988 Apr, 158(4), 986 - 8
Establishing a correct diagnosis of vulvovaginal infection; Kaufman RH; Vulvovaginitis is a common problem and a prime reason for physician consultation . The organism most frequently responsible for vulvovaginal infection is Candida albicans, and in a large majority of cases identification of the causative organism and diagnosis are easy to establish . Recurrent or persistent infection, however, presents a perplexing diagnostic problem that usually can be solved with the use of appropriate supportive laboratory tests and awareness of the distinguishing features of the possible etiologic agents . Problems in diagnosis or complications in treatment are usually due to concurrent infection by two or more organisms or to treatment without proper identification of the infectious agents.

Oral Surg Oral Med Oral Pathol, 1988 Apr, 65(4), 421 - 6
Oral hairy leukoplakia among HIV-positive intravenous drug abusers: a clinicopathologic and ultrastructural study; Ficarra G et al.; During a prospective investigation of oral lesions of 120 consecutive patients positive for human immunodeficiency virus, belonging to the intravenous drug abuser risk group and other risk categories, we observed hairy leukoplakia (HL) in 23 cases (19%) . The median age of the patients was 27 years (range, 20 to 50 years) . Twenty patients were men and three were women . All but two of the twenty three patients used intravenous drugs for a median period of 6 years (range, 5 to 18 years) and were involved in several episodes of needle sharing . Eight men were also bisexual, one man was homosexual, and one man was hemophiliac and bisexual . Eleven patients had asymptomatic infection, five had lymphadenopathy syndrome, six had AIDS-related complex, and one had acquired immunodeficiency syndrome . In all patients, HL lesions were localized on the lateral borders of the tongue . In twelve patients, the lesion was unilateral, and in eleven patients, it was bilateral . Microscopically, hyperparakeratosis and the presence of koilocytes were observed in all cases . Surface candidiasis could be detected with staining with periodic acid-Schiff in two thirds of the cases . In four cases, electron microscopy showed the presence of intracellular and extracellular hyphae of Candida albicans in the parakeratin layer associated with coccobacilli in the spaces between surface epithelial cells . The spinous layer included koilocytes, which had a clear cytoplasmic matrix, sparse organelles and tonofilaments, and dispersed chromatin . These cells were found to be infected by a herpes-type virus in all cases examined . There was no ultrastructural evidence of human papillomavirus in the nuclei of the epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Infect Immun, 1988 Apr, 56(4), 792 - 801
Factors influencing the interaction of Candida albicans with fibroblast cell cultures; Merkel GJ et al.; The interaction of Candida albicans clinical isolates with primary and established fibroblast cultures was studied . The intent was to determine whether yeast adherence and invasion of nonendothelial cell monolayer cultures could be quantitated reproducibly and whether this system could be used for future studies on yeast pathogenesis . Our results demonstrated that specific interactions between the yeast cells and fibroblasts only occurred at 37 degrees C and correlated with the germination process . Fluorescent-antibody staining indicated that invasion or tight associations between the germinating yeast cells and mammalian cells occurred after less than 3 h of incubation . Yeast adherence was estimated radiometrically and trypsin-resistant interaction with individual mammalian cells (infection) was measured microscopically after inoculated monolayer cells were detached with trypsin . We demonstrated that both types of association were time dependent at 37 degrees C; neither was affected by the concentration of glucose used to grow the yeast cells . Primary and established fibroblast cell lines were equally susceptible to infection, but primary cells appeared to have more yeast-binding sites . Fibroblasts maintained in confluent culture for an extended period of time also appeared to have more binding sites, and while not quantitatively more susceptible to infection, the older cells were more susceptible to infection-related cell death . An established kidney epithelial cell line (MDCK) was not susceptible to either type of yeast interaction, indicating that the yeast-fibroblast associations were specific.

J Oral Pathol, 1988 Apr, 17(4), 158 - 63
Resolution of candidal lesions of the dorsal rat tongue by ketoconazole; Allen CM et al.; The purpose of this study was to determine whether the mucosal alterations of the dorsal rat tongue produced by Candida albicans infection were reversible upon treatment with the antifungal drug ketoconazole . Following experimentally-produced infection, 17 rats showed clinical evidence of persistent lesions over a period of 20 weeks . Eight of these animals were then treated with ketoconazole daily for 2 weeks (20 mg/kg/day) . Appropriate non-infected controls and ketoconazole-only controls were also maintained . Five weeks after the ketoconazole treatment, all animals were killed and the dorsal tongues evaluated clinically and histologically . Control groups showed no abnormalities . Of the 8 animals in the treated-lesion group, all showed lesional resolution, while only 2 of the 9 animals in the untreated-lesion group showed resolution of their lesions (p = 0.002) . These findings indicate that the epithelial changes produced by this candidal isolate for this period of time are reversible.

J Clin Pharm Ther, 1988 Apr, 13(2), 151 - 7
Microbial contamination and growth in total parenteral nutrition solutions; Lawrence J et al.; TPN bags (196) and giving sets were subjected to microbiological examination following administration within a busy nutrition ward . Of these, five (2.6%) were found to be contaminated with coagulase-negative Gram-positive cocci . In all but one instance the contamination was restricted to the terminal ends of the giving sets rather than to the nutrition bag itself . Isolation of micro-organisms from the ward environment suggested that the contamination had arisen extrinsically during the setting up of the infusions . Isolates from the contaminated products, together with type species of Escherichia coli and Candida albicans, were examined with respect to their growth requirements and used to challenge four TPN formulations . Growth and survival of the organisms was monitored for up to 21 days . In all instances significant numbers of organisms were recovered after 72 h . Significant growth of the Staphylococcal isolate and C . albicans occurred over the initial 48-72 h incubation, this appeared to be greater in extent for the lipid-containing formulations . The temperature of storage of the formulation was the major determining factor for microbial growth and survival . No survivors were recovered, however, from any formulation after 21 days.

Histochem J, 1988 Apr, 20(4), 215 - 21
A comparison of the highly selective fluorescence staining of fungi in tissue sections with Uvitex 2B and Calcofluor White M2R; Wachsmuth ED; The selective fluorescence staining of two fungi, Candida albicans and Blastomyces dermatitides, with Uvitex 2B and Calcofluor White M2R was studied in deparaffinized and frozen sections of mouse kidney and lung . Both fluorochromes emitted maximally at about 430 nm, independent of the mounting media (Kaiser's gelatin or Entellan) . In addition to fungi, both fluorochromes also stained elastic fibres . The fluorescence intensity remained unchanged after storage of sections for more than 6 months in conventional slide boxes . The two fluorochromes showed the following differences: Calcofluor faded 1.25 times faster than Uvitex when illuminated with ultraviolet light . Calcofluor showed a greater affinity for tissues in general, and red cells and renal tubular casts in particular . Counterstaining of deparaffinized sections with Hemalum and Eosin reduced the fungi fluorescence and suppressed the general background fluorescence . However, it led to an intensification of Eosin staining and the fluorescence of red cells in Calcofluor-stained sections but not in Uvitex-stained ones . Similarly, the background fluorescence in frozen sections was reduced by Evans Blue, although elastic fibres still fluoresced after staining with Calcofluor . The degree of staining selectivity, and thus the contrast produced within a histological specimen, was greater with Uvitex 2B than with Calcofluor White M2R.

J Med Vet Mycol, 1988 Apr, 26(2), 79 - 92
Influence of growth conditions on Candida albicans adhesion, hydrophobicity and cell wall ultrastructure; Kennedy MJ et al.; The effect of cultivation in 13 media (10 complex, and three synthetic), as well as altering growth conditions, on Candida albicans adhesion, cell surface hydrophobicity and cell wall ultrastructure was studied . Adhesion of C . albicans to buccal epithelial cells (BECs) was significantly modified by all of the factors tested, particularly growth medium . In general, optimal adhesive activity for C . albicans was observed when the cells were grown in defined media (depending on the carbohydrate used) and/or at 25 degrees C . Moreover, significant differences in adhesion to BECs were noted when C . albicans was grown in the same complex medium from different manufacturers and in different batches of medium from the same manufacturer . Electron microscopy revealed significant differences in surface topography and cell wall ultrastructure of C . albicans grown in different media but none of these differences, including presence or absence of an outer floccular layer, appeared to correlate with the adhesive changes noted, which raises questions regarding the location and nature of the Candida adhesin(s) . Likewise, cell surface hydrophobicity could not be correlated with adhesion to BECs but may have influenced yeast coadhesion . The results indicate that Candida adhesion is highly dependent upon the cultivation conditions of the yeast cells tested, and may explain discrepancies in the literature regarding the biochemical nature of the surface component(s) responsible for C . albicans adhesion.

J Med Vet Mycol, 1988 Apr, 26(2), 127 - 31
Nutritional factors determine germ tube formation in Candida albicans; Holmes AR et al.; Following a short (3 h) period of carbon starvation, exponential phase yeast cells of Candida albicans rapidly (T50 45 min) formed germ tubes in a glucose/ammonium ion solution . The presence of both a sugar (glucose, sucrose or galactose) and a nitrogen source (ammonium ion or an amino acid metabolized via glutamate) was critical for morphogenesis.

J Periodontol, 1988 Apr, 59(4), 249 - 53
Nonspecific and specific immune responses in a child with Down's syndrome and her sibling . A case report; Reuland-Bosma W et al.; In a child with Down's syndrome (DS) and her sibling, host immune responses were evaluated under experimental gingivitis conditions . The children live in the same environment under identical conditions . In the DS child an earlier and more extensive gingival inflammation than in her sibling had been observed . Investigation of nonspecific host defense mechanisms revealed identical results in both children for the phagocytosis and intracellular killing of Candida albicans by polymorphonuclear leukocytes in crevicular washings (CR-PMNs), in blood (PB-PMNs) and blood monocytes . Furthermore, CR- and PB-PMNs were able to secrete identical amounts of hydrogen peroxide upon stimulation . The chemotactic response of PB-PMNs in the DS child was impaired, however . The results of the studies performed on parameters of specific host defense mechanisms showed low blastogenic responses to phytohemagglutinin (PHA) and pokeweed (PWM) by lymphocytes of the DS child as compared with her sibling . Also a lack of immune regulation leading to prolonged helper/inducer cell activation on a local (gingival) and circulation level and a less pronounced T-cell depression in PB were shown . Together, these differences observed in specific and nonspecific host response mechanisms may be responsible for the earlier and more extensive gingival inflammation found in the DS child.

J Hosp Infect, 1988 Apr, 11(3), 278 - 85
Evaluation of three disinfectants after in-use stress; Isenberg HD et al.; Solutions of 2.0% and 3.4% glutaraldehyde, and of 0.5% phenate with 0.18% glutaraldehyde were stressed with a microbial and organic soil load for the periods advocated by the respective manufacturers . The disinfecting efficacy of the stressed solutions was challenged with Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus subtilis, Mycobacterium bovis (BCG), a water Mycobacterium sp . and Candida albicans . The three disinfectants were active against the fast-growing bacteria in appropriate dilutions; lesser dilutions of the glutaraldehyde solutions killed the mycobacteria and the yeast, while stressed phenate with glutaraldehyde did not . One hour exposure of the stressed disinfectants failed to kill the spore preparations while reducing the number of survivors.

Pediatr Res, 1988 Mar, 23(3), 293 - 7
The ontogeny of pulmonary defenses: alveolar macrophage function in neonatal and juvenile rhesus monkeys; Kurland G et al.; Using the technique of bronchoalveolar lavage, we isolated alveolar macrophages (AM) from the lower respiratory tract of newborn (1-4 days of age), infant (6-10 days of age), juvenile (3-6 months of age), and adult rhesus monkeys . The AM thus obtained were assayed in vitro to determine their chemotactic, phagocytic, and candidicidal capabilities . The predominant (greater than or equal to 89%) cell type in bronchoalveolar lavage effluent in all ages was the AM . Chemotaxis, phagocytosis, and killing of Candida albicans were markedly impaired in neonatal AM as compared with those from infants, juveniles, and adults . AM chemotactic activity achieved normal adult values by 6 days of age . Phagocytosis, and to a lesser extent candidicidal activity, were significantly improved in 6-day-old animals, but adult levels were still not achieved even by 6 months of age.

J Med Microbiol, 1988 Mar, 25(3), 213 - 20
The inhibitory effect of serum on the growth of Torulopsis glabrata; Petrou MA et al.; Normal human plasma and serum were found to inhibit the growth of Torulopsis glabrata and, to a lesser extent, other yeasts . The factor responsible for the inhibition of T . glabrata was not dialysable, was heat stable at 56 degrees C for up to 4 h and could be partly removed by absorption with viable T . glabrata but not Candida albicans . It was fungistatic at low concentrations and fungicidal at high concentrations, stable up to 4 years between -20 degrees C and -70 degrees C, but for only a few weeks at 4 degrees C . Studies with Cohn fractions of serum showed that the inhibitory components were in either the alpha or beta globulin fraction or both . The combined effects of transferrin and IgM accounted for about 70% of the total inhibition observed . We were unable to identify the component responsible for the residual inhibition of growth . The inhibitory effect was totally neutralised by tetracyclines, quinolones, sulphamethoxazole and by very low concentrations of polyenes, imidazoles and 5-fluorocytosine.

Am J Surg, 1988 Mar, 155(3), 498 - 502
Colonic interposition for benign esophageal disease . Long-term clinical and endoscopic results; Isolauri J; Replacement of the esophagus for benign disease requires familiarity with the long-term results of various esophageal substitutes . In the present study, 60 esophageal reconstructions for benign disease using colonic interposition have been presented . The operations were performed mainly without thoracotomy, using both antiperistaltic and isoperistaltic colonic segments . There were no differences in swallowing ability between patients with antiperistaltic and patients with isoperistaltic interpositions . Regurgitation symptoms, however, seemed to be somewhat more common and more difficult in patients with antiperistaltic colonic transpositions . Endoscopic signs of colitis were common, but they did not correlate with regurgitation symptoms . Bacterial cultures from the transplanted colon mainly revealed the usual mouth organisms . Candida albicans was frequently found in the fungal samples . There were no differences in the results between patients with follow-up periods of more and less than 2 years . The clinical results were good or fair in a great majority of the patients.

Zentralbl Bakteriol Mikrobiol Hyg {A}, 1988 Mar, 268(1), 62 - 73
Production and characterization of monoclonal antibodies against secretory proteinase of Candida albicans CBS 2730; Borg M et al.; We describe the production and characterization of three murine monoclonal antibodies (M1-M3) which are directed against different epitopes of the secretory aspartic proteinase of Candida albicans CBS 2730 . All antibodies belonged to the IgM class, and they recognized denatured enzyme . Only antibody M1 was capable to react with the active proteinase . Differential reactivity was also observed with a large fragment of the proteinase of C . albicans . All antibodies recognized the corresponding proteinase of C . tropicalis 293 both in the active, and in the denatured state . Denatured porcine pepsin was also recognized by all three antibodies . However, active pepsin was recognized only by antibodies M1 and M2 . The antibodies did not inhibit enzymatic activity, and they were not suited for immunofluorescence detection of proteinase on fungal cells . However, employing Western blot analysis, proteinase antigen was detected by antibody M 1 in the serum of a patient suffering from candidal pneumonia . The circulating proteinase antigen was found to be bound to patient's IgM . Implications for the use of monoclonal antibodies in the serodiagnosis of candidosis, and first experiences with other monoclonal anti-proteinase antibodies are discussed.

J Inorg Biochem, 1988 Mar, 32(3), 163 - 9
Synthesis and microbicidal activity of N-(2-substituted) phenyl ureas and their metal complexes; Sharma RC et al.; N-2-carboxyphenyl urea (CPU), N-2-hydroxyphenyl urea (HPU), and N-2-mercaptophenyl urea (MPU) and their Cu(II), Ni(II), Zn(II), Co(II), and Mn(II) complexes were synthesized and characterized by elemental analysis, molecular weight determination, molar conductance, IR and electronic spectral data, and magnetic measurements . Antibacterial activity of these ligands and their metal complexes was determined on gram positive (Staphylococcus aureus) and gram negative (Escherichia coli) bacteria at 35 degrees C . Antifungal activity was determined on common fungi viz . Aspergillus niger, A . nidulense, and Candida albicans by the serial dilution method at 28 degrees C . A considerable increase in the biocidal activity of these ligands on being coordinated with the metal ions was reported in terms of their minimum inhibitory concentration (MIC) values.

Antimicrob Agents Chemother, 1988 Mar, 32(3), 327 - 30
Interference with effects of amphotericin B on Candida albicans cells by 2-chloroethyl-1-nitrosoureas; Brajtburg J et al.; Two nitrosoureas, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) and 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU), with strong carbamoylating and weak alkylating activities, interfered with the induction of potassium leakage and lethal action of amphotericin B (AmB) on Candida albicans . 2-Cyclohexyl isocyanate, the product of decomposition of CCNU, and 2-chloroethyl isocyanate, the product of decomposition of BCNU, also interfered with the anticandidal actions of AmB . In contrast, two nitrosoureas with weak carbamoylating and strong alkylating activities, 1-(2-chloroethyl)-3-(2,6-dioxo-3-piperydyl)-1-nitrosourea and 2-{3-(2-chloroethyl)-3-nitrosoureido}-D-glucopyranose, did not affect AmB action against C . albicans . These results indicate that the inhibitory action of CCNU and BCNU on the anticandidal effects of AmB is associated with the carbamoylating activity of these nitrosoureas.

J Clin Microbiol, 1988 Mar, 26(3), 459 - 63
Diagnosis of systemic candidiasis by an enzyme-linked dot immunobinding assay for a circulating immunodominant 47-kilodalton antigen; Matthews R et al.; A dot immunobinding assay based on the detection of the immunodominant 47-kilodalton (kDa) antigen of Candida albicans is described for the serological diagnosis of systemic candidiasis . It was compared with a reverse passive latex agglutination test and a dot immunobinding assay with total unfractionated hyperimmune serum to C . albicans . Use of the 47-kDa antigen-specific probe increased both the sensitivity and specificity of the assay system . Patients with systemic candidiasis were detected earlier in the course of the infection . The rate of detection of systemic C . albicans infections in neutropenic patients was 77% compared with 55% with total antibody in the dot immunobinding assay and 29% with the latex test . All three assay systems were positive in over 73% of infected patients who were not neutropenic . The 47-kDa antigen-specific probe was relatively specific to C . albicans . Antibody probes to the immunodominant antigens of other yeasts might be incorporated in the same dot immunobinding assay to detect systemic candidiasis caused by other species of yeasts.

Clin Chem, 1988 Mar, 34(3), 539 - 43
Preparation of monoclonal antibodies reactive with beta-1,2-linked oligomannosyl residues in the phosphomannan-protein complex of Candida albicans NIH B-792 strain; Tojo M et al.; Hybridomas obtained by fusing the spleen cells of BALB/c female mice hyperimmunized with heat-killed yeast-form cells of Candida albicans NIH B-792 strain and a mouse myeloma cell line, P3X63Ag8.653, produced antibodies to beta-1,2-linked oligomannosyl residues in the phosphomannan-protein complex of the parent cells . Most of these monoclonal antibodies were IgM, but about 10% of the hybridomas produced IgG1 immunoglobulins . Ascites fluid from BALB/c mice inoculated with an IgG1-producing hybridoma showed different precipitability with the phosphomannan-protein complexes of three representative C . albicans strains, with NIH B-792 (serotype B) greater than NIH A-207 (serotype A) greater than J-1012 (serotype A, formerly serotype C) . In contrast, a rabbit polyclonal antiserum to C . albicans NIH B-792 cells was unable to distinguish these same complexes . This ascites fluid agglutinated the heat-killed cells of three Candida strains, but not those of three others or of Torulopsis glabrata IFO 0622 . The other ascites fluids, containing antibodies of the IgM class, agglutinated cells from three C . albicans strains and also C . tropicalis IFO 0587 cells.

J Med Chem, 1988 Mar, 31(3), 650 - 6
Synthesis and anticandidal properties of polyoxin L analogues containing alpha-amino fatty acids; Khare RK et al.; Analogues of polyoxin L containing amino acids with saturated fatty acid like side chains were synthesized from the benzyloxycarbonyl-protected alpha-amino fatty acid p-nitrophenyl ester and uracil polyoxin C . Transfer hydrogenolysis using palladium black and formic acid gave diastereomeric, dipeptidyl polyoxin L analogues containing alpha-aminooctanoic acid (3), alpha-aminododecanoic acid (4), or alpha-aminohexadecanoic acid (5) as the amine terminal residue in 40-60% yield . Diastereomers of 3 and 5 were resolved by using high-performance liquid chromatography on a reversed-phase column and designated as 3a, 3b and 5a, 5b . Analogues 3-5 were excellent inhibitors of chitin synthetase from Candida albicans; 4, the best inhibitor, had an ID50 of 0.5 microM . The L,L diastereomers of 3 and 5 were 1-2 orders of magnitude more potent chitin synthetase inhibitors than their D,L homologues . None of the synthetic polyoxin L analogues inhibited transport of trimethionine, but 3a, 4, and 5b caused decreases of 71%, 87%, and 83%, respectively, in the initial rate of uptake of dileucine . Compounds 3-5 were significantly more stable to peptidase degradation than polyoxin L analogues containing naturally occurring alpha-amino acids . Compound 4 inhibited growth of C . albicans in culture at 40-80 micrograms/mL . All other analogues were less potent antifungals . The results suggest that synthetic polyoxins can be designed to have increased affinity for a peptide transport system and to have increased stability against intracellular degradation in C . albicans.

Proc Natl Acad Sci U S A, 1988 Mar, 85(5), 1452 - 6
A Candida albicans dispersed, repeated gene family and its epidemiologic applications; Scherer S et al.; Candida albicans causes a wide variety of infections but can readily be isolated from the skin and mucosa of healthy individuals . To enable high-resolution epidemiologic studies on this common pathogen, a species-specific DNA probe has been isolated from its genome . There are approximately equal to 10 copies of the sequence dispersed among the chromosome-sized DNA molecules resolved by pulsed-field electrophoresis . New DNA polymorphisms in this gene family arise at high rates . As a consequence, this probe will readily distinguish strains from different patients in the same hospital and from various sites in individual patients . The DNA polymorphisms detected by using this probe are largely due to internal changes in members of the family rather than movement to new genomic locations . This suggests recombination or gene conversion rather than transposition as the mechanism producing the observed variation.

J Appl Bacteriol, 1988 Mar, 64(3), 265 - 72
The influence of pyrithione on the growth of micro-organisms; Khattar MM et al.; Pyrithione was active against a range of micro-organisms, the most resistant being Gram-negative bacteria . The growth curves for Klebsiella pneumoniae and Bacillus licheniformis showed a drug-dependent lag phase . Candida albicans grew with a drug-dependent growth rate . EDTA antagonized the effects of pyrithione.

Clin Exp Immunol, 1988 Mar, 71(3), 377 - 82
Cell-mediated immune responses to Plasmodium falciparum antigens in adult Gambians; Riley EM et al.; Peripheral blood mononuclear cells from clinically immune Gambian adults were assayed for in vitro proliferation in response to crude and partially purified Plasmodium falciparum antigens . Lymphoproliferative responses to malaria antigens, lectin mitogens and Candida albicans were compared with those of control donors with no previous exposure to malaria . Cells of malaria-immune individuals were significantly more responsive to conconavalin A, and less responsive to phytohaemagglutinin, than cells from the control donors in both non-immune human serum and autologous serum . Cells from a proportion of immune donors proliferated in response to soluble malaria antigens but a substantial minority did not . Young adults and women were over-represented in the non-responding population . Responses to soluble malaria antigens were depressed in autologous serum compared with normal human serum . Both immune and control cells produced low levels of gamma-IFN when stimulated with crude P . falciparum schizont antigens . Approximately half the immune donors, and none of the controls, produced significant levels of gamma-IFN in response to purified soluble malaria antigen or malaria parasite culture supernatant . There was no direct correlation between lymphoproliferation and gamma-IFN production.

J Antimicrob Chemother, 1988 Mar, 21(3), 333 - 43
Selective inhibition of 14 alpha-desmethyl sterol synthesis in Candida albicans by terconazole, a new triazole antimycotic; Isaacson DM et al.; Terconazole, a new broad spectrum antimycotic triazole derivative, has been shown to have potent activity against Candida albicans in vitro and to be effective in animal models of yeast infections . The present study explored a possible mechanism of anticandidal activity of terconazole . The compound inhibited production of 14 alpha-desmethyl sterols (e.g . ergosterol) in C . albicans at concentrations (IC50 = 3-6 x 10(-9) M) lower than those inhibiting the in-vitro growth of the yeast . There was concomitant accumulation of methylated sterols, (e.g . lanosterol), which are considered detrimental to normal yeast cell membrane function . Terconazole stimulated incorporation of 14C-acetate into triglycerides, but had no other effect on C . albicans lipid metabolism . At concentrations greater than or equal to 10(-6)M terconazole inhibited the oxidation of 14C-acetate into 14CO2 in C . albicans although the mechanism for this effect remains unclear . These data indicate that terconazole is a specific inhibitor of yeast C-14 desmethyl sterol production in C . albicans . Furthermore, terconazole reduced cytochrome P-450 levels in yeast microsomes at concentrations 10,000-fold below those at which it showed effects on rabbit liver microsomes . These data indicate a species specificity for the biochemical actions of terconazole . The C-14 alpha-desmethylase system in yeast cell membranes is cytochrome P-450 associated . Thus, terconazole, was a potent inhibitor of C-14 desmethyl sterol synthesis . This effect could contribute to the anticandidal activity of the drug.

Can J Microbiol, 1988 Mar, 34(3), 224 - 8
Interaction of Candida albicans with genital mucosa: effect of sex hormones on adherence of yeasts in vitro; Kalo A et al.; Findings from our previous studies revealed a correlation between the level of adherence in vitro of Candida albicans to human exfoliated vaginal epithelial cells (VEC) and the hormonal status of the cell donors . In the present study we investigated the effect of the sex hormones estradiol, estriol, progesterone, and testosterone on the binding of the yeasts to HeLa cell lines and VEC in vitro . Monolayers of HeLa cells were exposed to the hormones and yeasts under controlled conditions . The number of adherent yeasts per square millimetre of HeLa cell monolayers and the percentage of VEC with adherent yeasts was estimated by microscopic counts . The results showed that the tested sex hormones affected at various degrees the adhesion of yeasts to HeLa cells or VEC . Progesterone had the most marked effect, leading to a significant increase in the number of adherent yeasts to HeLa cells or in the percentage of adhesion of VEC . In addition, VEC were separated on Percoll gradients into the two cell types: superficial (S) and intermediate (I), cell types which appear physiologically under increased serum levels of estradiol or progesterone, respectively . Adhesion assays with the separated cell populations revealed an increased binding capacity of the I cells . The finding that progesterone increased the adherence of yeasts to genital mucosa and that VEC of the I type have a higher capacity to adhere the yeasts is compatible with our previous observation that increased numbers of I cells, appearing under high level of progesterone, are found in situations known to have predisposition to vaginal candidiasis.(ABSTRACT TRUNCATED AT 250 WORDS)

Ann Inst Pasteur Microbiol, 1988 Mar-Apr, 139(2), 171 - 88
{Cytologic analysis of the expression of an epitope carried by glycoproteins excreted by Candida albicans}; Cailliez JC et al.; The present study concerns an epitope identified by a monoclonal IgM, named 5B2, generated against the parasitic phase of Candida albicans . The epitope was previously shown to be carried by excreted C . albicans glycoproteins and to be present in the sera of patients suffering from systemic candidiasis . The cytological analysis of the epitope expression was investigated in 3 different yeast strains: the C . albicans strain from which 5B2 was generated (VW.32); a C . albicans mutant, deficient in cell wall mannans (KD.102); and a Saccharomyces cerevisiae strain . Immunofluorescence assays using IgM-5B2 showed discontinuous labelling with the VW.32 strain and no labelling with the 2 other yeast strains; however, the superficial structures of the 3 strains reacted homogeneously with ConA . Ultrastructural immunodetection experiments performed with the VW.32 cells, using gold-conjugated monoclonal antibody, revealed the presence of the epitope in the vacuolo-vesicular system, the periphery of the cytoplasm, the periplasmic space and the cell wall . Under the same conditions, cells from the KD.102 strain only exhibited weak cytoplasmic labelling whereas the presence of the epitope in S . cerevisiae blastoconidia was restricted to the vesicles . Competition and double labelling experiments with IgM and ConA showed that the epitope, distributed on the great majority of VW.32 glycoproteins, is shared by a lesser proportion of the KD.102 glycoproteins and only by some vesicular glycoproteins of S . cerevisiae . Inhibition of the N-glycosylation process of the VW.32 strain by tunicamycin resulted in the absence of cytokinesis and germ tube formation . In such cells, epitope 5B2 was no longer expressed on the bud surface . These cytological results concerning the C . albicans epitope are discussed in relation to recent, more general biochemical data on the yeast glycosylation process.

J Am Dent Assoc, 1988 Feb, 116(2), 187 - 92
Juvenile juxtavermilion candidiasis: yet another form of an old disease?
Bouquot JE, Fenton SJ.
Five cases of a chronic, self-limiting Candida albicans infection of the lip vermilion and juxtavermilion skin in young persons are presented . These infections typically appeared as erythematous, pruritic, yellow crusting plaques of the juxtavermilion skin, with or without desquamation of vermilion surfaces . Evidence of intraoral candidiasis, especially loss of filiform lingual papillae, was present in several cases . The disorder mimics the early stage of chronic mucocutaneous candidiasis but remains within a few millimeters of the mucocutaneous junction and affected individuals appear (with a possible exception) to be immune competent . Mild trauma apparently triggers the infection . The authors emphasize that a scientifically sound cause-and-effect relationship between this new disease and Candida albicans is not herein established and present these cases in the hope that others will thereby be identified and a firmer causal relationship be established.

Z Kardiol, 1988 Feb, 77(2), 130 - 1
{Pneumopyopericardium--a rare complication following surgical correction of an "upside-down stomach"}; Peters W et al.; The follow-up period after surgery of an upside-down stomach in a 53-year-old patient was complicated by a pneumopyopericardium due to Candida albicans and Enterococcus . Therapy was performed by pericardial drainage . Local instillations of Mezlocillin (100 mg/l) and Amphotericin B (1 mg/l, Candida-MIC = 0.1 mg/l), over a period of 10 days and followed by a systemic antimycosis with 5-Flucytosin (0.14 g/d/kg over 5 days) and Amphotericin B (0.3 mg/d/kg over 11 days) led to recovery . Six months after discharge from the hospital, echocardiography revealed only a thickened pericardium without hemodynamic disorders.

J Med Vet Mycol, 1988 Feb, 26(1), 57 - 65
Correlation between the sterol composition of membranes and morphology in Candida albicans; Cannon RD et al.; The opportunistic pathogenic fungus Candida albicans was examined in three distinct morphological forms: yeast, mycelia, and stunted mycelia obtained by growing cells under mycelial-inducing conditions in the presence of ketoconazole at concentrations below the MIC . Comparison of the sterols of the parental strain with those from a mutant unable to produce mycelia, by TLC and GLC, showed no significant differences in sterol composition between the yeast and mycelial morphological forms . However, ketoconazole-treated cells possessed a lower ergosterol content and an increased amount of 14-methylated sterol precursors . The effect of ketoconazole on mycelial cells was quantitatively different from the effect on yeast cells in that the ratio of 4, 14-dimethylsterols to 4-methylsterols was significantly lower in the stunted mycelial morphological forms . A comparison of the effect of terbinafine on sterol biosynthesis and morphology suggests that the effect on ergosterol content is of greater importance than the increase in sterol precursors in determining cell shape.

J Med Vet Mycol, 1988 Feb, 26(1), 49 - 56
Oral carriage of Candida albicans, ABO blood group and secretor status in healthy subjects; Burford-Mason AP et al.; ABO blood group and secretor status were determined in healthy subjects in relation to oral carriage of Candida albicans, using a mouthwash technique to identify carriers and non-carriers . Of 100 subjects studied, 32% carried Candida, the main species isolated being C . albicans (94% isolates) . Carriage of C . albicans was significantly associated with blood group O (p less than 0.001) and independently, with non-secretion of blood group antigens (p less than 0.001), with the trend towards carriage being greatest in group O non-secretors . This suggests that in healthy subjects, blood group O and non-secretion of blood group antigens are separate and cumulative risk factors for oral carriage of C . albicans.

Chemioterapia, 1988 Feb, 7(1), 33 - 7
A study of the antifungal activity of LY121019, a new echinocandin derivative; Strippoli V et al.; LY121019 is a cyclic peptide antibiotic of the echinocandin group, which is characterized by strong anti-Candida activity (in particular against Candida albicans) as well as by low experimental toxicity . Its anti-Candida activity is thought to be due to an inhibition of the synthesis of beta-glucan, an essential cell wall polysaccharide . The different composition of culture media or the presence of animal serum did not show adverse effects on LY121019's anti-Candida activity and the addition of reducing compounds such as cysteine and hydroquinone did not manifest a negative influence . Analogously the anti-Candida activity was not influenced when C . albicans was grown under aeration . The activity of LY121019 was very high against the mycelial form of C . albicans even when this form was developed in the presence of animal serum.

Carbohydr Res, 1988 Feb 1, 172(2), 243 - 53
Structural studies of mannans from the cell walls of the pathogenic yeasts Candida albicans serotypes A and B and Candida parapsilosis; Kogan G et al.; A comparative study of three cell-wall mannans, of Candida albicans serotypes A and B and Candida parapsilosis, by means of methylation analysis supports a model of yeast mannans as having an alpha-(1----6)-linked backbone with some units (depending on the origin of the mannan) being substituted at O-2 with oligosaccharides joined by alpha-(1---2) and, to a lesser extent, by alpha-(1----3) glycosidic bonds . Branching points in the side chains of Candida albicans mannans were found in substantial proportions for the first time, and the corresponding branched hexasaccharides were isolated by means of acetolysis and subsequent gel filtration . 13C-N.m.r . spectroscopy of the mannans, as well as a 1H-n.m.r . spectroscopic study of the oligosaccharides obtained on acetolysis of the mannans, led to results that agreed with those of methylation analysis.

Zh Mikrobiol Epidemiol Immunobiol, 1988 Feb, (2), 87 - 91
{Interaction of Candida albicans with macrophages}; Karaev ZO et al.; Study of the in vitro interaction of mouse peritoneal macrophages with C . albicans has revealed that these macrophages, though easily phagocytizing C . albicans blastospores, are incapable of destroying the fungus . The phagocytic, but not candidostatic, activity of these macrophages has been found to depend on the conditions on their cultivation, as well as on the age and viability of fungal cells . The representatives of 7 C . albicans strains, obtained from various sources and stored at the museum for different spans of time, have shown practically no difference in the character of their interaction with mouse peritoneal macrophages.

J Rheumatol, 1988 Feb, 15(2), 362 - 5
Candida albicans infection of a prosthetic knee replacement: a report and review of the literature; Koch AE; A woman with rheumatoid arthritis who underwent total knee arthroplasty is described . The implant became infected with Staphylococcus epidermidis and she received a prolonged course of postoperative antistaphylococcal antibiotics . Four months postoperatively she developed a calf ulcer that grew Pseudomonas aeruginosa and required further antibiotic therapy . One year later she presented with a painful, swollen knee with radiographic findings suggesting loosening of the prosthetic knee implant . Arthrocentesis cultures grew Candida albicans . She was treated with arthrodesis, amphotericin B, 5-fluorocytosine, and ketoconazole and remains free of infection 21 months after removal of the prosthesis . The clinical course of 6 other cases of Candida prosthetic joint infections is reviewed.

Mycopathologia, 1988 Feb, 101(2), 77 - 83
Induction of germ-tube formation by Candida albicans in amino acid liquid synthetic medium at 25 degrees C; Sabie F et al.; Candida albicans (3153A) was found to exhibit extensive germ-tube and mycelial development at 25 degrees C when transferred from amino acid synthetic medium at pH 6 to medium of pH 7 . Significant germ-tube formation was detectable after approximately 8 h and in all experimental treatments, the peaks of maximal germination occurred at approximately 40-44 h . Such a transition was not only dependent on the initial pH of the medium but also on the glucose concentration and inoculum size . The optimum initial glucose concentration and inoculum size for maximal germ-tube development was 1.25% and 2 X 10(6) cells ml-1 respectively and above or below these values the extent of germ-tube formation was greatly reduced.

Mycopathologia, 1988 Feb, 101(2), 105 - 11
Disseminated cutaneous and peritoneal hyalohyphomycosis caused by Fusarium species: three cases and review of the literature; Rippon JW et al.; Three recent cases of hyalohyphomycosis caused by Fusarium sp . illustrate differing aspects of infections produced by these organisms . One patient was undergoing continuous ambulatory peritoneal dialysis when peritonitis developed caused by Fusarium moniliforme . Removal of the catheter and amphotericin B were used in successful management . In a neutropenic patient on therapy for leukemia, multiple persistent infections occurred including JK diptheroids, and Candida albicans sepsis . Finally, numerous florid skin lesions caused by Fusarium oxysporum developed even while the patient was receiving amphotericin B and he died . In a second neutropenic patient on treatment for leukemia, sinus and cutaneous lesions developed due to Fusarium . These resolved on amphotericin B therapy following the return of circulating neutrophils . The literature on Fusarium infections and aspects of the biology of the organism are reviewed.

Infect Immun, 1988 Feb, 56(2), 302 - 9
Variable expression of a surface determinant during proliferation of Candida albicans; Chaffin WL et al.; The surface expression of an antigenic determinant that is present in the cell wall of Candida albicans was investigated with monoclonal antibody 24 (MAb24), an immunoglobulin M MAb . The proportion of the cell population that expressed the epitope under different growing conditions was determined by indirect immunofluorescence microscopy . More than 90% of stationary-phase yeast cells of strain B311 grown at 28 degrees C expressed the antigen . Less than 50% of yeast cells grown exponentially at 28 degrees C or either growing or stationary-phase yeast cells cultivated at 37 degrees C expressed the epitope . Germ tubes, which were induced at 37 degrees C from stationary-phase yeast cells grown at 28 degrees C, expressed the determinant on the parent yeast but not the hyphal portion of the germ tube . The change in antigen expression by stationary-phase cells grown at 28 degrees C, when they resumed growth by bud formation, suggested that antigen expression was lost by cells in the inoculum prior to the first cell division . By using the same assay, strong positive reactions were observed in stationary-phase cultures of other isolates of C . albicans, C . guilliermondii, C . stellatoidea, and C . tropicalis, but not with isolates of C . krusei, C . parapsilosis, or Torulopsis glabrata . The identification of the antigenic determinant as a carbohydrate was based on three observations: (i) interaction with a mannan preparation from the same organism, (ii) sensitivity of the antigen to periodate but not proteases, and (iii) coincidence of the migration of antigen during electrophoresis with material which stained intensely with carbohydrate but not with protein reagents . These observations suggest that the expression of the antigenic determinant of MAb24 is dependent on the growth conditions, growth state, and morphology of the cell and that the topography of the cell surface is dynamic.

Microbiol Sci, 1988 Feb, 5(2), 58 - 63
The molecular genetics of Candida albicans; Kurtz MB et al.; Candida albicans, the major fungal pathogen of humans, is a diploid with no known sexual cycle . Recent genetic studies in C . albicans include the physical characterization of the genome, the development of systems for parasexual genetics, the cloning of Candida genes, and the development of methods for integrative and ARS-mediated transformation as well as gene disruption.

Antimicrob Agents Chemother, 1988 Feb, 32(2), 209 - 12
Activities of fluconazole (UK 49,858) and ketoconazole against ketoconazole-susceptible and -resistant Candida albicans; Hughes CE et al.; We have compared the activities of fluconazole and ketoconazole against ketoconazole-susceptible and -resistant strains of Candida albicans in a neutropenic-site rabbit model . Oral treatment with fluconazole resulted in much higher serum and extravascular concentrations of this antifungal agent than did comparable doses of ketoconazole . Fluconazole had no additional in vivo activity against the ketoconazole-susceptible strains; no fungicidal activity was observed with peak drug levels as high as approximately 75 micrograms/ml in the infection sites . Significant fungistatic activity against the ketoconazole-resistant strains was observed with fluconazole treatment (80 mg/kg), but not with less fluconazole (20 mg/kg) or with ketoconazole (approximately 67 mg/kg) . In vitro susceptibility tests separated the ketoconazole-susceptible strains from the ketoconazole-resistant strains, but the results were variable when the resistant strains were tested with fluconazole.

J Bacteriol, 1988 Feb, 170(2), 895 - 9
Opaque-white phenotype transition: a programmed morphological transition in Candida albicans; Rikkerink EH et al.; This paper reports that the opaque and white phenotypes of Candida albicans constitute a true high-frequency reversible transition system . The rDNA restriction fragment and orthogonal field alternating gel electrophoresis profiles of opaque and white phenotypes are indistinguishable, and a genetic marker introduced into a white strain is present in all opaque derivatives of this strain . Opaque and white derivatives appear markedly different on a bismuth indicator medium and differ in a number of other respects . We have used bismuth medium to examine the spontaneous and temperature-induced frequencies of transition from opaque to white . The temperature-induced transition from opaque to white does not occur when opaque cells are held in water.

Clin Immunol Immunopathol, 1988 Feb, 46(2), 284 - 93
Neutrophil accumulation and cutaneous responses in experimental cutaneous candidiasis of genetically complement-deficient mice; Wilson BD et al.; Mice deficient in the fifth component of complement were studied for their ability to respond to and clear experimental cutaneous Candida albicans infections . The complement-deficient animals took longer to clear the infections and developed a significantly greater delayed hypersensitivity response to Candida than did normal animals . However, although the serum of the complement-deficient animals was incapable of generating in vitro chemotactic activity for neutrophils after appropriate stimulation, the epidermal neutrophilic infiltrate in the Candida-infected skin of these animals was equivalent to that in the normal animals . The progression of the infection, including the early relocation of the invading Candida pseudohyphae to a more superficial site in the stratum corneum and the thickening of the epidermis itself, was also similar in the complement-deficient and normal animals . Therefore, although mice lacking the fifth complement component cannot generate complement-derived serum chemotactic factors and are somewhat less efficient in clearing experimental cutaneous candidiasis, the accumulation of neutrophils in the Candida-infected skin of these animals and their initial cutaneous responses to the infections are normal.

Biochem Biophys Res Commun, 1988 Jan 29, 150(2), 532 - 9
Temporal association of calcium mobilization, inositol trisphosphate generation, and superoxide anion release by human neutrophils activated by serum opsonized and nonopsonized particulate stimuli; Meshulam T et al.; We have investigated the involvement of phospholipase C mediated polyphosphoinositide turnover in activation of polymorphonuclear leukocytes by particulate stimuli . Results showed that stimulation of leukocytes with serum opsonized zymosan (ingestible particle), serum opsonized Candida albicans hyphae (noningestible particle), or nonopsonized hyphae was followed by a transient rise in cellular inositol phosphates as has been described for neutrophil activation via the formyl peptide receptor . The kinetics of inositol trisphosphate generation paralleled both the time course of changes in cytosolic calcium concentration and the onset of superoxide anion generation, suggesting that these may be related events.

Z Hautkr, 1988 Jan 18, 63(1), 57 - 9
{Granulocyte function in the aged}; Djawari D; 22 patients (10 female, 12 male) aged between 60 and 76 were tested in vitro with regard to granulocyte function (i.e., leucotaxis, chemotaxis, capability of phagocytosis, intracellular killing of bacteria, and oxidase reaction) . Most of the patients showed reduced chemotactic activity of the granulocytes, although the motility of these cells was normal . With regular phagocytosis of candida albicans cells--either active or heat-inactivated the intracellular killing rate of bacteria was clearly decreased in all cases . The intracellular oxidase activity of granulocytes always showed normal function.

Scand J Thorac Cardiovasc Surg, 1988, 22(2), 143 - 4
Acute atrophic glossitis after open-heart surgery; Bengtsson L et al.; The problem of Candida infections has become important in connection with transplant surgery and immunosuppression . To clarify the source of the postoperative acute atrophic glossitis (AAG) commonly seen in our department of cardiac surgery, 33 patients admitted for coronary artery bypass or valve replacement underwent clinical and microbiologic investigation before and after operation . None showed signs of AAG preoperatively, but 12 had cultures positive for Candida albicans, and in all 12 AAG appeared postoperatively . Six of the 21 patients with preoperatively negative cultures likewise had postoperative AAG . All 18 affected patients responded well to local nystatin treatment . No patient had disseminated candidiasis.

J Ethnopharmacol, 1988 Jan, 22(1), 25 - 31
Anti-infectious phytotherapies of the tree-savannah of Senegal (West-Africa) II . Antimicrobial activity of 33 species; le Grand A et al.; The screening of the antimicrobial activity of 33 medicinal plants from Senegal is reported . None of these plants showed activity against the gram-negative test bacteria and against Candida albicans . Extracts of Cnestis ferruginea and Voacanga africana showed strong activity against Aspergillus niger . The former plant was also active against dermatophytes . Twenty-five of the plants tested showed activity against gram-positive bacteria.

Early Hum Dev, 1988 Jan, 16(1), 27 - 33
Does gastric acid protect the preterm infant from bacteria in unheated human milk?
Usowicz AG, Dab SB, Emery JR, McCann EM, Brady JP.
Although preterm mother's milk has greater nutritional and anti-infective properties than donor milk, it may be highly contaminated with bacteria . We therefore asked three questions: what is the fate of these bacteria in the preterm infant's stomach, is gastric pH important, and what factors affect gastric pH? pH, colony count and bacterial identification were performed on the milk and on serial gastric aspirates in 20 preterm infants on 25 occasions . Seventeen milk samples grew bacteria, five potentially pathogenic and 12 non-pathogenic . Twelve of 25 prefeeding gastric samples were sterile, but following the feeding all the samples grew non-pathogenic bacteria and 70% grew potential pathogens . With time pH decreased and by 2-h samples with pH less than 3.5 had no bacterial growth; Candida albicans still flourished in a low pH (mean 2.8) . We concluded that a low gastric pH may be more important than the bacterial count of the milk . In a second study, 91 serial gastric pH measurements were made on 12 preterm infants . pH tended to decrease with increasing age and was significantly lower in infants fed exclusively human milk (2.7 vs . 3.6; human milk versus formula P less than 0.02) We speculate that human milk may influence gastric acid production and thus protect the preterm infant from bacteria in the milk.

Int Arch Allergy Appl Immunol, 1988, 86(2), 201 - 8
Inhalant allergies to fungi: reactions to bakers' yeast (Saccharomyces cerevisiae) and identification of bakers' yeast enolase as an important allergen; Baldo BA et al.; Forty-seven subjects diagnosed as having inhalant allergies to fungi were tested for allergic sensitivity to bakers' yeast . Skin prick tests with yeast extract showed that 35 subjects responded with wheal reactions that were at least 3 mm while 32 subjects were regarded as clearly RAST-positive to bakers' yeast antigens . Skin and RAST testing with purified enolase from bakers' yeast and comparisons with the whole yeast extract showed that the enzyme is a major allergenic component of the extract . This conclusion was supported by results of electroblotting studies . RAST inhibition experiments demonstrated allergenic cross-reactivity between bakers' yeast, bakers' yeast enolase and Candida albicans.

Gene, 1988, 63(1), 53 - 63
Isolation and characterization of a beta-tubulin gene from Candida albicans; Smith HA et al.; We report the isolation and nucleotide sequence determination of a beta-tubulin gene (TUB2) from the pathogenic dimorphic fungus Candida albicans . Nucleotide sequence analysis revealed that TUB2 encodes a protein of 449 amino acids (aa) with considerable sequence homology to beta-tubulins isolated from other fungal species . The nucleotide sequence of the C . albicans gene is 70% homologous to that of the Saccharomyces cerevisiae gene . The coding region for the C . albicans beta-tubulin gene is interrupted by two introns . The first intron occurs after the 4th aa and the second intron occurs after the 13th aa . A comparison with other fungal beta-tubulin genes indicates that the intron locations are highly conserved . Codon usage in the C . albicans TUB2 gene is nonrandom, as has been observed for other fungal beta-tubulin genes . The C . albicans TUB2 gene is transcribed to yield a 1.8-kb mRNA species . On the basis of genomic Southern-blot analysis, we conclude that C . albicans most likely possesses a single beta-tubulin gene.

Arch Dermatol Res, 1988, 280(3), 168 - 70
Phototoxicity of skin microorganisms tested with a new model; Faergemann J et al.; A new standardized method for testing phototoxicity of chemicals against microorganisms is described . The inoculum size of the microorganism, application of test chemicals, prediffusion time, incubation time and incubation period are defined . Staphylococcus aureus, S . epidermidis, Candida albicans, and Pityrosporum orbiculare were studied . Both 8-methoxypsoralen and trimethylpsoralen were phototoxic against all microorganisms tested, while tetracycline and doxycycline were not phototoxic . C . albicans may be chosen for phototoxicity testing because it has been used earlier, it is easy to maintain in culture, it grows easily when tested, and its pathogenicity is low . The phototoxicity of S . aureus, S . epidermidis, Pseudomonas aeruginosa, Propionibacterium acnes, C . albicans, and P . orbiculare against each other were also investigated . Only P . orbiculare was inhibitory . It inhibited the growth of S . aureus, S . epidermidis, and Ps . aeruginosa - both in the dark and after irradiation . The growth inhibition was markedly enhanced after UVA irradiation, indicating phototoxicity . The phototoxic effect of P . orbiculare may play a role in the ecology of the human skin flora.

Cytobios, 1988, 53(212), 7 - 17
Intracytoplasmic membrane configurations, vesicles and vesicular inclusions in Candida albicans; Rajasingham KC et al.; Ultrastructural studies of Candida albicans in its invasive form obtained from oral lesions of patients with acute chronic candidosis, candidal infection on chorio-allantoic membrane of chick embryo, and of organisms grown artificially, have demonstrated the presence of an intracytoplasmic membrane system, vesicles and vesicular inclusions, in varying degrees . These variations appear to be attributed to the environment, cultural conditions and the age of the organism . Their origin, structure and distribution are described.

Arch Microbiol, 1988, 149(4), 286 - 90
Regeneration of the cell wall in protoplasts of Candida albicans . A cytochemical study using wheat germ agglutinin and concanavalin A; Miragall F et al.; To assess the dynamics of synthesis of the wall by regenerating Candida albicans protoplasts deposition of chitin and mannoproteins were investigated ultrastructurally using wheat germ agglutinin conjugated with either horseradish peroxidase or colloidal gold, and Concanavalin A coupled to ferritin respectively . Freshly prepared protoplasts lacked wheat germ agglutinin receptor sites but after 1-2 h of regeneration, they were detected . After 4-5 h of regeneration, the cell wall showed a discrete structure which was only labelled with wheat germ agglutinin in thin sections . At this stage of regeneration the outermost layer of the wall was labelled with clusters of Concanavalin A-ferritin particles . After 8 h regeneration, the cell wall appeared compact, and homogenously marked with wheat germ agglutinin whereas only the surface layers appeared consistently labelled with Concanavalin A-ferritin . From these observations we conclude that C . albicans protoplasts are able to regenerate in liquid medium a cell wall consisting of a network of chitin fibrils and mannoproteins at least (glucan polymers were not determined in the present cytological study) . The former are the fundamental component of the inner layers at early stages of regeneration, whereas the latter molecules are predominant in the outer layers of the wall.

Mycopathologia, 1988 Jan, 101(1), 37 - 45
Development of amphotericin B liposomes bearing antibody specific to Candida albicans; Hospenthal DR et al.; Liposomes expressing external antibody specific for Candida albicans and encapsulating amphotericin B were developed and characterized in this study . Antibody was first modified by the covalent attachment of palmitic acid residues . Liposomes were produced by reverse-phase evaporation and modified antibody was incorporated into these liposomes via the hydrophobic interaction between the palmitic acid and the phospholipids composing the liposomes . The liposomes were characterized as to the amount of amphotericin B by spectroscopy and for the presence of antibody by protein analysis and secondary immunolabeling by fluorescent and electron microscopic methods . Immunogold labeling showed that the antibody was being expressed externally on the liposomes in the electron microscopic studies and the specificity of these liposomes for C . albicans was observed by secondary immunofluorescence.

J Biol Stand, 1988 Jan, 16(1), 33 - 43
A novel Candida albicans skin test antigen: efficacy and safety in man; Esch RE et al.; Yeast phase Candida albicans (ATCC No . 10231) was grown in a nonantigenic medium, harvested and lyophilized . Ammonium sulfate fractions of an aqueous extract of the lyophilized cells were evaluated and the fraction yielding the highest specific delayed cutaneous reactivity in sensitized guinea-pigs was used to prepare a C . albicans skin test antigen (CASTA) . The safety of the antigen was evaluated by measuring immediate and delayed (0.25, 6, 24, 48 and 72 h) cutaneous reactions in atopic and nonatopic human subjects . The outcome of three repetitive monthly Mantoux skin tests with 0.01-1 microgram antigen doses was used to test for booster effects in 14 subjects and to estimate a safe initial test antigen dose . The utility of a single skin test as a measure of cell-mediated immunity was evaluated in 40 healthy subjects . Reactor rates (greater than or equal to 2 mm, 48 h) of 40% and 85% were detected, respectively, with doses of 0.0316 and 1 microgram . Using a skin test reaction diameter greater than or equal to 5 mm at 48 h, the reactor rate was 50% for the 1-microgram dose . The only adverse reaction (45 mm, 0.25 h) was detected with the 1-microgram dose in an atopic subject who also exhibited exquisite scratch test reaginic hypersensitivity to C . albicans allergen . The prevalence of other adverse reactions to this antigen compared favorably with that to other antigens used for recall antigen testing . These studies suggest the 1-microgram CASTA dose can be used for effective, safe recall antigen skin tests.

Arch Dis Child, 1988 Jan, 63(1), 53 - 7
Infective endocarditis in neonates; O'Callaghan C et al.; Five patients with neonatal infective endocarditis were reviewed, two of whom survived . Infection was caused by Staphylococcus aureus in four and by Candida albicans in one . All cases of bacterial endocarditis had clinical signs of septicaemia, positive blood cultures, thrombocytopenia, microscopic haematuria, and heart murmurs . Three developed skin abscesses early in their illnesses . Three patients had two dimensional echocardiographic studies that showed bacterial vegetations . One of these studies was done before the heart murmur could be heard . We suggest that echocardiography in conjunction with the clinical picture described may help in making an early diagnosis of endocarditis in neonates.

JPEN J Parenter Enteral Nutr, 1988 Jan-Feb, 12(1), 49 - 52
Effect of nucleotide restriction and supplementation on resistance to experimental murine candidiasis; Fanslow WC et al.; The influence of dietary nucleotides on susceptibility to candidiasis in mice was studied using two criteria: animal survival and recovery of viable Candida albicans organisms from the kidney and spleen . One-month-old mice were placed on one of five diets with varying nucleotide content . The results show that mice maintained on a nucleotide-free diet (NF) exhibit a significantly decreased mean survival time and a significantly increased viable organism recovery in the spleen following intravenous injection of graded inocula of C . albicans compared to mice fed diets containing RNA or uracil as a nucleotide source.

J Allergy Clin Immunol, 1988 Jan, 81(1), 6 - 16
An open study of auranofin in the treatment of steroid-dependent asthma; Bernstein DI et al.; To determine the efficacy of oral gold in asthma, 20 patients with steroid-dependent asthma received auranofin at a dose of 3 mg by mouth, twice daily, in a 24-week open clinical trial . Prospective evaluation of bronchial responsiveness to methacholine was determined before and 8 and 16 weeks after initiation of auranofin therapy . Serial spirometry (FEV1 and FVC), lung volumes, and diffusing capacities (single breath carbon monoxide diffusing capacity of the lungs) were measured before and at 10 and 20 weeks after treatment . All subjects were required to record concomitant medications, symptom scores, and morning and evening peak expiratory flow rates . In vitro immunologic studies performed before and after 8 and 20 weeks of auranofin therapy included leukocyte histamine release in response to antihuman IgE, lymphocyte blast transformation in response to concanavalin A and phytohemagglutinin, and leukocyte inhibitory factor activity in response to Candida albicans and tetanus toxoid antigens . In 18 patients evaluated, there were no significant differences between baseline and posttreatment spirometry, single breath carbon monoxide diffusing capacity of the lungs, and lung volumes . At week 16 of treatment, the steroid cumulative dose or the total prednisone dose administered from 7 days before through 10 days after each methacholine test day decreased from a mean of 293 +/- 125 mg at baseline to 192 +/- 115 mg . At week 16, nine of 18 patients (50%) exhibited decreased methacholine responsiveness as defined by a more than one-half log10 increase in the concentration of methacholine causing a 20% decrease in FEV1 . A significant correlation (r = 0.60) was observed between the increase in the concentration of methacholine causing a 20% decrease in FEV1 and the decrease in steroid cumulative dose after 16 weeks of treatment . Leukocyte histamine release to anti-IgE exhibited significant reductions from baseline at week 20 to 10(-2) (p less than 0.002) and at 10(-3) (p less than 0.005) dilutions . At week 20, leukocyte inhibitory factor activity in response to Candida increased from baseline at the 0.1 mg per well (p = 0.025) and 1 mg per well (p = 0.05) concentrations; similarly, the responses to tetanus toxoid increased at the 1 mg per well (p less than 0.05) and 0.1 mg per well (p less than 0.01) concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)

Clin Orthop, 1988 Jan, (226), 235 - 9
Infection with Candida albicans of a total knee arthroplasty . Case report and review of the literature; Levine M et al.; Infection with Candida albicans of a total knee arthroplasty developed in an immunosuppressed 52-year-old woman with rheumatoid arthritis who initially presented with clear drainage from the incision, which cultured negative initially . Successful treatment consisted initially of debridement and a course of intravenous antibiotics, followed by staged arthrodesis with an intramedullary rod.

Spec Care Dentist, 1988 Jan-Feb, 8(1), 13 - 5
Oral complications in a patient with acute lymphocytic leukemia: a report of case; Beiraghi S et al.; Herpes viruses and Candida albicans are among the most common opportunistic pathogens infecting patients with neoplastic disease, especially those patients receiving cancer chemotherapy . Herpes virus infections have increased as treatment of oncological disease has become more aggressive and immunosuppression disorders have become more prevalent . Herpes simplex virus on the lips and mouth of a patient receiving chemotherapy can progress to multiple lesions in the mouth, larynx, and in rare instances can lead to pneumonitis and widely disseminated infection . The management and dental findings of a 13-year-old patient with acute lymphocytic leukemia are described.

Int J Immunopharmacol, 1988, 10(7), 851 - 4
The effect of RU 41740 on the in vitro maturation of human B-cells; Durandy A et al.; We have tested the effect of a Klebsiella pneumoniae extract, RU 41740, and its lipopolysaccharidic fraction (LPS-LAP) on the in vitro activation of human B-cells . Two models have been used: the polyclonal activation induced by pokeweed mitogen and the specific antibody production to mannan, a polysaccharide extracted from the cell wall of Candida albicans . We have shown that RU 41740, and especially its lipopolysaccharidic fraction, significantly increases the production of immunoglobulins and specific antibodies . This effect is mediated by T-lymphocytes, since preincubation of isolated T-cells, but not of non-T-cells, resulted in the same effect . Together with the known enhancing effect of LPS-LAP on T-cell proliferation, these data strongly suggest that LPS-LAP increases the production of B-cell-activating lymphokines by T-cells.

Cytobios, 1988, 56(226-227), 157 - 62
Paper chromatographic characterization of an extracellular biologically active compound from Coelastrum sphaericum var . dilatatum; Accorinti J et al.; A non-cytotoxic, wide antiviral spectra compound was isolated from the lyophilized media of axenic cultures of the green alga Coelastrum sphaericum var . dilatatum . After acid hydrolysis, polyenic-like fractions were liberated from the same compound with inhibitory effect against Candida albicans . Biochromatographic and spectrophotometric results demonstrated that the product included a glycosidic fraction associated with a nucleotidic component.

J Med Vet Mycol, 1988, 26(5), 277 - 83
Candida concentrations in the vagina and their association with signs and symptoms of vaginal candidosis; Odds FC et al.; Among 106 women harbouring yeasts in the vagina and with other causes of genital pathology excluded, there was a statistically significant association between numbers of yeasts recovered semi-quantitatively from vaginal swabs and symptoms of pruritus and signs of abnormal vaginal discharge but no association between yeast numbers and other individual symptoms or signs of vaginal candidosis, including patients' own subjective assessment of abnormal vaginal discharge . The presence of yeasts detectable by direct microscopic examination was statistically associated with pruritus, discharge and vaginitis . There was no relationship between numbers of vaginal yeasts and histories of antibiotic or oral contraceptive usage or the stage of the menstrual cycle . Distributions of Candida species and Candida albicans biotypes were not statistically related to any symptoms, signs or other factors . The results of this study suggest that vaginal pathology caused by Candida species may be related to the quantity of the fungus in the vagina and that only pruritus and objectively assessed vaginal discharge are firm clinical indicators of Candida infection.

Eur J Gynaecol Oncol, 1988, 9(6), 502 - 14
Immunological changes in human breast cancer; Contreras Ortiz O et al.; In 38 breast cancer patients were examined the following immune system parameters: total and active T lymphocytes; killer cells; bastogenic response to Phytohaemaglutinin; leucocyte migration inhibition test with autologous tumor extract; serum immunoglobulins and phagocytosis and intracellular killing of Candida albicans . The immunological evaluations were made in pre-surgery and after each 3 months, during 18 months . In stage I practically there was no difference with controls . The active T lymphocytes were significant decreased until 15 months post surgery in stage II and in all samples stages III and IV . The response to Phytohaemaglutinin was diminished in all samples of stages II, III and IV . A recognition and sensitiveness to tumoral antigen were observed until 6 months post surgery in stage I and during checking time in the others stages . Respect to the phagocytic function only the intracellular killing mechanism failed at 3 months post surgery.

Pediatrie, 1988, 43(3), 209 - 12
{Multifocal Candida albicans osteoarthritis in an infant}; Lamireau T et al.; The authors report a case of candidal arthritis and osteomyelitis in a five-month-old child . Parenteral nutrition with central catheter, broad-spectrum antibiotherapy, repeated gastrointestinal surgery are the main risk factors . The prognosis for this bone and joint infection is favourable . Using 5-fluorocytosine alone is not recommended because of rapid gain of resistant various pathogenic fungi and the risk of therapeutic failure.

Dermatologica, 1988, 177(2), 115 - 9
A case of Candida albicans skin abscess associated with intravenous catheterization; Mochizuki T et al.; We report a case of Candida albicans skin abscess, which developed on the left knee of a 59-year-old male, who had been bedridden for the past 2 months because of subarachnoid haemorrhage . The route of the infection was considered to be an intravenous catheter that had been inserted into the left great saphenous vein at the medial malleolus . The prolonged systemic administration of antibiotics and corticosteroids, as well as prostration, were suspected to be the factors that led to the infection . The patient was successfully treated with intravenous miconazole and subsequent high-dose oral amphotericin B therapy.

Acta Derm Venereol Suppl (Stockh), 1988, 136, 1 - 45
Studies on leg and foot ulcers; Hansson C; The medical records of patients with leg and foot ulcers caused by vascular disorders were investigated in Goteborg in 1980 . The prevalence was estimated to be about 0.3% . The median age of all patients was 73 years . Sixty per cent of the patients were women . There were small differences in the number of leg and foot ulcers cases in each age-group per 1000 inhabitants between men and women . The prevalence of ulcers increased rapidly with age, especially after the age of 70 . Seventeen per cent of the patients had ulcers on the medial side of the leg around the ankle only and about 30% on the feet only . Leg and foot ulcer patients were treated by several different specialties and mostly (76%) as outpatients only . From the total of 1377 ulcer patients, 350 patients, who had consulted the Department of Dermatology in 1980 were asked to come for an interview in 1984 . Ulcers had been present at some time in each of the years 1981, 1982 and 1983 in 44% of the interviewed patients . During 1980, 24% of the ulcers healed and did not recur before the end of the study . During the follow-up period (3.5 years) 27% of the patients had died . The mortality rate for the leg and foot ulcer patients during the follow-up period was twice as high for both men and women as for the same age groups in the population of Goteborg, during the same years . The risk of dying from ischaemic heart disease was also approximately doubled, but the risk of dying from malignancies was the same . Compression bandages are the most important in the treatment of venous leg ulcers . The pressure under a bandage is proportional to the number of bandage layers with constant stretch . A simple method of regulating the highest comfortable sub-bandage pressure was developed . The number of bandage layers was increased gradually with the same stretch in 30 patients . The reproducibility of the method was tested for different nurses . Compression bandages are often applied for long-term treatment as double bandages . Six women treated for long periods with double bandages for venous leg ulcers developed painful, bright red, glistening skin lesions with pustules, denuded skin and scales as in intertriginous candidiasis . Cultures showed growth of Candida albicans and antimycotic treatment resulted in relief of pain and healing of skin lesions.(ABSTRACT TRUNCATED AT 400 WORDS)

Immunol Cell Biol, 1988 Jan, 66 ( Pt 3), 231 - 7
Murine candidiasis: strain dependence of host responses after immunization; Ashman RB et al.; After recovery from acute infection with live Candida albicans, both CBA/H and BALB/c mice show increased resistance to colonization by the organism . However, the 'susceptible' CBA/H mice develop much stronger protective responses than do 'resistant' BALB/c mice . This is manifested particularly as a substantial amelioration of the severity of the lesions in the brain, and a very marked reduction in the number of fungal units therein . Analysis of granulocyte function in normal and immune mice of the two strains tended to exclude this as a basis for the different patterns of susceptibility and resistance.

Folia Biol (Praha), 1988, 34(5), 316 - 29
Induction and regulation of cytotoxic T cells by microbial antigens and recombinant interleukin 2; Piccolella E et al.; The proliferation and development of cytotoxic T cells was investigated in human peripheral blood mononuclear cell (PBMC) cultures stimulated with an antigenic extract from Candida albicans (MPPS), or with the purified protein derivative from Mycobacterium tuberculosis (PPD), or with human recombinant interleukin 2 (rIL-2) . Microbial antigen- and rIL-2-induced cytotoxic T cells were able to lyse both natural killer (NK) sensitive and resistant targets . No correlation was observed between the development of T cell cytotoxicity and interferon (IFN) production in vitro . The addition of anti-class II monoclonal antibodies at the beginning of MPPS/PPD-stimulated cultures inhibited the cell proliferation, IFN production and T cell cytotoxicity, while all these cellular activities were not inhibited by anti-class II antibodies in rIL-2-stimulated cultures . Finally, antibodies to class I determinants inhibit T cell cytotoxicity, suggesting a role of such determinants in the development of the non-adaptive immunity to microbial infections.

Acta Neurochir Suppl (Wien), 1988, 43, 130 - 4
The response of peripheral blood mononuclear cells of glioma-bearing patients to stimulation with microbial antigen and IL-2: proliferation and IFN-gamma production; Maleci A et al.; 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.

Nephrol Dial Transplant, 1988, 3(1), 84 - 6
Systemic and disseminated candidiasis complicating acute renal failure; Stevens PE et al.; One case of disseminated Candida albicans infection and two cases of systemic C . albicans infection in patients with acute renal failure are described . The predisposing factors and management implications are discussed and therapeutic recommendations made.

Acta Stomatol Croat, 1988, 22(4), 311 - 7
{Candida albicans in leukokeratotic lesions of oral mucosa}; Vidas I et al.; The potential presence of Candida albicans in oral leukokeratotic lesions, also entailing the need of additional antimiotic therapy, has been quite extensively discussed in literature . Therefore, the aim of this study was to assess the prevalence of Candida albicans isolates in subjects with oral leukoplakia as well as of candidal leukoplakia according to oral mucosa regions . The study included 60 subjects, mean age 46 years . A study group had 28 subjects with oral leukoplakia, whereas a control group comprised subjects free of any pathological alterations of oral mucosa . In all subjects, a clinical oral examination was performed and material for microbiological analysis taken . Following cultivation and incubation, tests of identification and microbiological analysis were carried out on the material thus grown . Results of the study revealed that Candida albicans was present in 67.9% of subjects with oral leukoplakia, which is the highest percentage reported on so far, and in 28.1% of subjects without any pathologic alterations of oral mucosa . The prevalence of candidal leukoplakia was found to be highest in oral mucosa, followed by lips, tongue and sublingual mucosa . Thus, these findings appear to clearly confirm the need of additional use of antimicotics, along with antikeratotic therapy of leukoplakia.

Arch Oral Biol, 1988, 33(8), 617 - 9
Degradation of human dentine collagen by an enzyme produced by the yeast Candida albicans; Hagihara Y et al.; An extracellular collagenolytic enzyme separated from a culture medium of this pathogenic yeast was found to attack undenatured predentine collagen as seen in scanning electron micrographs . After treatment with the enzyme at pH 4.0, but not by that acidity alone, dentine tubules were less easily distinguished and the collagen fibres were less well-organized.

Arch Oral Biol, 1988, 33(8), 567 - 73
A comparison of the inhibition of blastospore viability and germ-tube development in Candida albicans by histidine peptides and ketoconazole; Santarpia RP 3rd et al.; Synthetic homologous peptides of L-histidine, ranging in length from 3 to 64 amino-acid residues, suppressed blastospore viability . Killing activity was dependent upon the peptide molecular size and concentration, and the time of cell exposure to the agent, but was independent of cell concentration in the range 10(5)-10(7) colony-forming units (c.f.u.) per ml . A 25 amino-acid residue polypeptide, similar to the human parotid salivary histidine-rich peptide (HRP-5), also affected yeast viability . Its killing effect was dependent upon the number of c.f.u . in the assay, as well as contact time with the blastospores and the final peptide concentration . HRP-5 inhibition increased with rising pH in the range 5-7.4, in contrast to poly-L-histidine and ketoconazole, which had optimal candidacidal activity at about pH 6 . Poly-L-histidine, HRP-5, and ketoconazole each prevented conversion of blastospores to germ tubes, but their rank order of effectiveness varied with the assay selected . In N-acetylglucosamine-supplemented fetal calf serum, poly-L-histidine and HRP-5 were more effective inhibitors than ketoconazole, but the reverse was true in amino-acid-supplemented glucose beef-extract medium . Reduction of both germ-tube numbers and germ-tube size by HRP-5 was concentration-dependent.

Cytobios, 1988, 55(222-223), 171 - 84
Variations for susceptibilities to ultraviolet induced cellular inactivation and gene segregation among protoplast fusion hybrids of Candida albicans; Sarachek A et al.; Hybrids of the naturally diploid, asexual and opportunistically pathogenic yeast, Candida albicans, can be obtained artificially by protoplast fusion . Evidence is presented that gene conversion and reciprocal recombination contribute to ultraviolet (UV)-induced segregations of heterozygous markers from both diploid and hybrid strains, and that hybrids also segregate through induced chromosome loss . Heterozygous diploid strains independently derived from the same wild-type diploid stock were alike in post-UV survival and segregational responses, and the organization of a four gene linkage group identified in diploids from the segregant products of reciprocal recombinations was transmitted intact to all hybrids from fusions between diploids of isogenic or nonisogenic backgrounds . However, hybrids arising independently from a given fusion cross differed significantly from each other in post-UV survival, absolute ability to segregate some parental markers, frequency of gene segregation, and proclivities for each of the three mechanisms of gene segregation . The bearings of the genetic backgrounds of parental strains and of growth temperatures during hybrid formation on each of these variables are described . The findings emphasize that awareness of the intrinsic heterogeneities of fusion hybrids is essential for reliable application of the protoplast fusion procedure to genetic analysis of C . albicans.

Dev Genet, 1988, 9(4-5), 615 - 28
A comparison of high frequency switching in the yeast Candida albicans and the slime mold Dictyostelium discoideum; Soll DR et al.; Recently, high frequency switching systems have been identified in the infectious yeast Candida albicans and the cellular slime mold Dictyostelium discoideum . In C . albicans, cells can switch at spontaneous frequencies as high as 10(-2) between seven general colony morphologies in the case of strain 3153A or between two major phenotypes in the white-opaque transition in strain WO-1 . In the latter system, dramatic changes occur in cellular phenotype as well . In D . discoideum, cells can switch at spontaneous frequencies of roughly 10(-2) between a number of colony phenotypes which include alterations in developmental timing, blocks at particular morphogenetic stages, morphological aberrations, and aggregation-minus . In the C . albicans and D . discoideum switching systems, the following characteristics are shared: 1) a limited number of switch phenotypes; 2) heritability; 3) high frequency reversibility; 4) low and high frequency modes of switching; and 5) ultraviolet (UV) stimulation of switching of cells in a low frequency mode of switching.

J Med Vet Mycol, 1988, 26(5), 315 - 8
Degradation of bovine achilles tendon collagen by Candida albicans proteinase; Kaminishi H et al.; Candida albicans, when cultivated in a medium containing insoluble bovine achilles tendon as a nitrogen source, was able to produce a collagen degrading proteinase . The degradation of achilles tendon collagen by the proteinase was verified by morphological change and the release of hydroxyproline . The proteinase activity was inhibited by pepstatin.

Med Cutan Ibero Lat Am, 1988, 16(4), 285 - 90
{Mycotic and bacterial flora in patients with nail disorders}; Arreaza F et al.; 249 patients with a possible diagnosis of onychomycosis were studied . The majority of patients with diagnosis of mycosis had a different cause In our study only 96 cases (38.5%) had proved mycotic infection, 4 (1.6%) had a bacterial infection and the rest had different causes of lesion such as trauma, contact dermatitis, psoriasis, etc . The mycotic lesions were usually caused by dermatophytes: Trichophyton rubrum, T . mentagrophytes and T . tonsurans . The 2nd most frequent agents were years most of them Candida albicans . The 3rd group was formed by opportunist fungi . Most of the isolated bacterial were of cutaneous saprophytic flora, and in only 4 cases Pseudomonas aeruginosa was found.

Crit Rev Biotechnol, 1988, 8(2), 121 - 9
Candida proteinases and candidosis; Douglas LJ; Infections caused by the opportunistic yeast pathogen, Candida albicans, are becoming increasingly important . Superficial Candida infections, particularly those of the mouth and vagina, are very common; for example, candidal vaginitis plaques millions of women worldwide, often proving refractory to treatment . Systemic candidosis is much rarer, but it is an important hazard of modern medical procedures such as transplant surgery, i.v . hyperalimentation, and immunosuppressive therapy . One significant virulence factor of C . albicans is its ability to secrete extracellular acid proteinase . This attribute is shared by C . tropicalis and C . parapsilosis, but not by other less pathogenic Candida species . The enzymes produced by these yeasts are all carboxyl proteinases capable of degrading secretory IgA, the major immunoglobulin of mucous membranes . Some have keratino- or collagenolytic activity . Two secretory proteinases of C . albicans have been purified and characterized; their properties are reviewed . Possible applications of this work to the treatment and diagnosis of candidosis are discussed.

J Med Vet Mycol, 1988, 26(4), 207 - 17
Fluorescence microscopic studies on mitochondria and mitochondrial nucleoids in a wild-type strain and respiratory mutants of Candida albicans; Ito-Kuwa S et al.; A wild-type strain and two respiratory mutants of Candida albicans were examined for mitochondria and mitochondrial nucleoids (mt-nucleoids) using the fluorescent dyes, 2-(4-dimethylaminostyryl)-1-methylpyridinium iodide (DASPMI) and 4', 6-diamidino-2-phenylindole (DAPI) . Rapidly growing cells of the wild type possessed one or a few giant branched mitochondria that were intensely stained with DASPMI . When a bud emerged, an end of the giant mitochondrion extended into the bud and the mitochondrion was divided and partitioned into mother and daughter cells by cytokinesis . Cell cycle-associated fragmentation or fusion of mitochondria were not demonstrated . The mutant KRD-8, that possesses cristate mitochondria but respires at a lower level, was shown to contain one or a few, less stainable giant mitochondria per cell . DASPMI failed to stain cells of the mutant KRD-19 which lacks cytochrome aa3 and cristate mitochondria . About eight and 10 mt-nucleoids were detected as discrete fluorescent spots in DAPI-stained cells of the wild type and KRD-8, respectively . KRD-19 cells also possessed mt-nucleoids, although the number of mt-nucleoids per cell seemed to be smaller than that of the wild type . In all the strains, mt-nucleoids existed discretely throughout the budding cycle, and the increase of their number per cell appeared to correlate with the cellular volume but not with nuclear division.

J Basic Microbiol, 1988, 28(3), 185 - 96
Development of genetic maps of non-conventional yeasts; Ogrydziak DM; Numerous methods based on classical genetics have been developed for the genetic mapping of yeasts . Recombinant DNA technology and technology for electrophoretic separation of chromosomes make new approaches possible . The state-of-the-art in genetic mapping of Saccharomyces cerevisiae will be briefly reviewed . Then the availability and application of genetic mapping methods to non-conventional yeasts will be surveyed . Development of the genetic maps of the asexual diploid Candida albicans and of the heterothallic yeast Yarrowia lipolytica will be discussed in more detail.

J Gen Microbiol, 1988 Jan, 134 ( Pt 1), 241 - 6
Carrot phytoalexin alters the membrane permeability of Candida albicans and multilamellar liposomes; Amin M et al.; The biochemical basis for the antimicrobial effect of the carrot phytoalexin 6-methoxymellein (6-MM) was examined . At fungistatic concentrations 6-MM retarded the ability of Candida albicans to incorporate radioactive thymidine, uridine and leucine into biopolymers . When C . albicans was incubated with 6-MM, 260-nm-absorbing materials and 3H-labelled compounds leaked from the cells . The inhibitory effects of 6-MM on cell growth and membrane functions were, however, reduced as the concentration of divalent metal cations added to the medium was increased . 6-MM interacted with multilamellar liposomes constituted from phosphatidylcholine, cholesterol and dicetyl phosphate, or from phosphatidylcholine only, resulting in the release of glucose trapped in these liposomes . These results suggest that 6-MM exerts its toxic effects on susceptible cells as a result of its interaction with their membranes and disturbance of membrane-associated functions.

Chemotherapy, 1988, 34(5), 430 - 6
In vitro and ex vivo enhancement of nonspecific phagocytosis by cefodizime; Fietta A et al.; The in vitro and ex vivo effects of cefodizime on some functional activities of both human neutrophils and monocytes were studied . In vitro experiments were performed with antibiotic concentrations ranging from 1 to 200 micrograms/ml . For the ex vivo study, 7 adult healthy controls were treated intravenously with 4 g/day of cefodizime for 6 days . We found that the drug modulated phagocytosis frequency and index when nonopsonized zymosan and heat-killed Candida albicans were used as phagocytic challenge both in vitro (from 25 micrograms/ml) and ex vivo 12 h after the last administration of cefodizime . No effect on the other phagocyte functional parameters was shown . The in vitro enhancement of nonspecific phagocytosis was demonstrated both in the presence of cefodizime and when phagocytes and particles were separately incubated with the drug.

Chemotherapy, 1988, 34(5), 411 - 4
Studies on antifungal agents . 17 . Effects of the C-5-substitution on the in vitro activity of novel 3,5-substituted isoxazolidines; Dormer PA et al.; A number of novel 5-(substituted thiomethyl)-3-phenyl-3-(1H-imidazol-1-ylmethyl)-2- methylisoxazolidine derivatives were prepared and evaluated in vitro for antifungal activity in solid agar cultures against Trichophyton rubrum, Aspergillus fumigatus and Candida albicans . The effect of the 5-(substituted thiomethyl) group on the degree and scope of activity was studied and compared to that of the corresponding 5-phenoxymethyl and 5-{(substituted phenyl)thio(or amino)methyl} derivatives.

Leuk Res, 1988, 12(7), 545 - 50
The effect of 13-cis retinoic acid on hematopoiesis in human long-term bone marrow culture; Bleiberg I et al.; The modulatory effect of 13-cis retinoic acid (RA) on the growth, differentiation and function of hematopoietic cells in human long-term cultures was studied . RA (5 X 10(-8) M) induced enhancement of myeloid progenitor cell growth in the non-adherent layer throughout 6 weeks of incubation while it did not affect the number of myeloid progenitors in the adherent layer . The vitamin did not alter the differentiation pattern of colony forming unit-culture (CFU-C) . The addition of RA to cultures for 5 weeks did not alter the cellular composition of the adherent layer . Prolonged exposure of hematopoietic cells to RA did not affect the functional activity of neutrophils and macrophages, i.e . the cells were active in phagocytosing Candida albicans (CA).

Int Arch Allergy Appl Immunol, 1988, 86(4), 400 - 6
Production and characterization of a murine monoclonal antibody to Aspergillus fumigatus antigen having IgG- and IgE-binding activity; Kurup VP; By employing hybridoma technology, a monoclonal antibody against Aspergillus fumigatus was produced . This antibody, isotyped as IgM k, reacted with 12 of 16 antigens extracted from 9 different A . fumigatus strains . This antibody also reacted with all 3 Aspergillus flavus antigens studied, but not with Aspergillus niger, Aspergillus terreus, Penicillium notatum or Candida albicans antigens . Western blot analysis indicated that this antibody reacted with two concanavalin A (Con-A) binding bands of the A . fumigatus antigen extract . The specific binding antigens were isolated using monoclonal antibody affinity chromatography . When used in immunoassay this fraction demonstrated strong IgG and IgE antibody-binding activities against patient sera . The antibody levels against the purified fraction were significantly higher in patients' sera than in normal controls . The purified fraction demonstrated comparable reactivity with the crude A . fumigatus extract against patient sera, but the former has the added advantage of being pure and standardizable for dependable and reproducible results.

Int Arch Allergy Appl Immunol, 1988, 85(1), 130 - 2
Lack of induction of IgE and IgG antibodies to yeast in humans immunized with recombinant hepatitis B vaccines; Wiedermann G et al.; Yeast-derived hepatitis B vaccines (partially purified or highly purified) at different dosages and a plasma-derived hepatitis B vaccine (control) were injected into 50 young volunteers 3 times at monthly intervals . Before and 4 weeks after this series of immunizations, blood samples were drawn and tested for presence of IgE and IgG antibodies against yeast antigens . No rise in IgE antibodies against Saccharomyces cerevisiae antigens nor in IgG antibodies against Candida albicans antigens was found . Together with former clinical results this underlines the experience that type I and type III reactions against putative yeast contaminants apparently play no major role after immunization with recombinant hepatitis B vaccines.

J Infect Dis, 1988 Jan, 157(1), 38 - 46
An iC3b receptor on Candida albicans: structure, function, and correlates for pathogenicity; Gilmore BJ et al.; Heretofore, the existence of membrane receptors for biologically active fragments of mammalian complement proteins has been confined to mammalian cells, where these receptors serve to protect the host by triggering multiple aspects of the phagocytic response to microbial invasion . In this study, we show that surface receptors for the C3 fragment iC3b are present on the yeast Candida albicans, where they promote the pathogenicity of this organism by inhibiting phagocytosis . These receptors share homology with the alpha-chain, but not with the beta-chain, of neutrophil receptors for iC3b, as determined by the binding of monoclonal antibodies, and are induced by mycelial transformation of the yeast and by high concentrations of glucose . Blockade of these receptors by monoclonal antibodies significantly augments phagocytosis for those strains studied . By binding iC3b noncovalently, these receptors impair phagocytic uptake of C . albicans by human polymorphonuclear leukocytes.

Infect Immun, 1988 Jan, 56(1), 252 - 8
Identification of C3d receptors on Candida albicans; Calderone RA et al.; Pseudohyphal but not yeast forms of Candida albicans possess both iC3b and C3d receptors, as determined by rosetting with erythrocytes carrying iC3b (EAC3bi) or C3d (EAC3d) . Rosetting with EAC3d was markedly reduced when pseudohyphae were heat killed or treated with trypsin or pronase but was not inhibited by several saccharides or aminosaccharides, including alpha-methyl-D-mannoside, or by pretreatment of pseudohyphae with concanavalin A . However, mannoproteins obtained by concanavalin A affinity chromatography of whole pseudohyphal extracts inhibited the attachment of EAC3d to C . albicans, whereas soluble (nonmannosylated) proteins were less active . Thus, although the C3d receptors appeared to be glycosylated, the oligosaccharide component of the receptor was apparently not involved in the recognition of C3d . To isolate these receptors, whole-cell extracts were separated by DEAE-Trisacryl chromatography . Fractions that inhibited rosetting were pooled and affinity purified by C3d-Thiol-Sepharose chromatography . The eluate from this affinity column inhibited attachment of C . albicans to EAC3d . Monoclonal antibodies to C . albicans were prepared, and three of these antibodies blocked rosetting . Western blotting (immunoblotting) with these antibodies indicated the presence of 62- and 70-kilodalton receptors for C3d in the extracts purified by C3d affinity chromatography and separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

Chemotherapy, 1988, 34(6), 444 - 7
Studies on antifungal agents . 18 . In vitro activity of 5,5-disubstituted-3-phenyl-3-(1H-imidazol-1-ylmethyl)-2-methy lisoxazol idines and related compounds; Mullen GB et al.; The in vitro antifungal activity of a series of novel 5,5-disubstituted-3-phenyl-3-(1H-imidazol-1-ylmethyl)-2-methyli soxazolidines and related compounds against Trichophyton rubrum, Aspergillus fumigatus and Candida albicans was studied . The screening was performed in solid agar cultures and some structure-activity relationships involving the C-5-substitution pattern are discussed.

J Med Vet Mycol, 1988, 26(5), 285 - 99
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; Bistoni F et al.; 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.

Drugs Exp Clin Res, 1988, 14(5), 341 - 5
Itraconazole activity against fungal germination; Strippoli V et al.; Itraconazole was found to be superior to ketoconazole in its antifungal activity in vitro against Hyphomycetes and Candida . In particular, complete inhibition of germination of Candida albicans and Aspergillus spp . by a lower dose of itraconazole can explain the better activity in vivo of this drug.

Pediatr Pulmonol, 1988, 5(1), 1 - 5
Use of bronchoalveolar lavage in immunocompromised children with pneumonia; Pattishall EN et al.; Because pneumonia in the immunocompromised host presents a diagnostic dilemma to the pediatrician, we prospectively studied the use of bronchoalveolar lavage (BAL) with flexible fiberoptic bronchoscopy in 14 immunocompromised children with pneumonia over a 5-month period . The children received immunosuppressive agents because of organ transplants, cancer, or systemic lupus erythematosus . A diagnosis was made by BAL in 10 (71%) of the 14 children . Pathogenic organisms included Pneumocystis carinii in six, cytomegalovirus (CMV) in two, Aspergillus fumigatus in one, and a mixed infection of Candida albicans and CMV in one . There were no complications . Because BAL by flexible fiber-optic bronchoscopy is a rapid and safe procedure and a diagnosis can be made in a majority of cases, we recommend its use in immunocompromised children with pneumonia before resorting to lung biopsy.

Int J Immunopharmacol, 1988, 10(2), 169 - 73
In vitro effects of fluconazole (UK-49,858) and ketoconazole on mouse lymphocyte proliferation and on Candida blastospore destruction by human polymorphonuclear leukocytes; Senior DS et al.; The effects of fluconazole, a novel antifungal compound with a bis-triazole structure, were compared with those of ketoconazole on mitogen-induced DNA synthesis by cultured mouse lymphocytes, and on the destruction of fungal (Candida albicans) blastospores by human polymorphonuclear leukocytes . Fluconazole had little or no effect on concanavalin A- or lipopolysaccharide-induced lymphocyte proliferation at concentrations at which ketoconazole caused marked inhibition of the response to both these mitogens . Similarly, fungal cell killing by polymorphonuclear leukocytes was substantially depressed by ketoconazole but was unaffected by fluconazole . In addition, therefore, to having excellent in vivo antifungal activity, fluconazole, unlike ketoconazole, has been shown to have no inhibitory effect in two in vitro assays of immune function.

Virchows Arch A Pathol Anat Histopathol, 1988, 412(6), 533 - 42
Ultrastructural and immunohistochemical findings in oral hairy leukoplakia; Zhang XL et al.; Three cases of HL from the lateral border of the tongue of male homosexual AIDS patients were investigated by thin section electron microscopy . Keratinocytes contained condensed chromatin in their pyknotic nuclei and a few organelles in the oedematous cytoplasm . Chromatin was in close association to the nuclear membrane and showed a punched-out appearance . Particles typical of the herpes virus group were abundant in the upper two thirds of the epithelium in all three cases . Virus particles were seen frequently in the nuclei of the ballooned keratinocytes, but rarely in cells containing Candida albicans . Viral nucleocapsids were observed budding at the inner nuclear membrane, thereby acquiring the prospective viral envelope . Complete, enveloped virions were found in the endoplasmic reticulum and in the extracellular space . These virions were identified immunohistochemically as Epstein-Barr virus (EBV) using two monoclonal antibodies directed against EBV capsid and membrane antigen, respectively . Candida albicans was observed in the stratum corneum and in the upper layer of the stratum spinosum . Special cytoplasmic tubular structures arranged in parallel bundles were found in koilocytotic cells in addition to characteristic membrane structures composed of undulating convoluted membranes . Epithelial basement membranes were always intact.

Virchows Arch B Cell Pathol Incl Mol Pathol, 1988, 56(1), 1 - 4
Visualization of fungi in histological sections; Wachsmuth ED; Deparaffinized kidney sections from mice infected with Candida albicans and lung sections from mice infected with Blastomyces dermatitides were stained with the stilbene derivative, Uvitex 2B (1%), and counterstained with haemalum and eosin . Fungi selectively stained with Uvitex 2B are visualized by blue fluorescence under incident illumination with ultraviolet light . Simultaneous or consecutive illumination with transmitted light permits the assignment of fluorescent fungi to haemalum-eosin-stained structures in the section . The most practical means of achieving a high optical contrast with Uvitex 2B in sections and good haemalum-eosin staining is to use the established haemalum-eosin technique, but with a solution containing both 1% eosin and 1% Uvitex 2B in place of eosin alone . Since Uvitex 2B stains all fungi investigated so far, it affords a simple, sensitive and inexpensive method of selectively detecting opportunistic fungal infections in conventional histopathology.

Cell Biol Int Rep, 1988 Jan, 12(1), 35 - 40
5-Azacytidine accelerates yeast-mycelium conversion in Candida albicans; Pancaldi S et al.; The effect of the DNA demethylating agent 5-azacytidine (5-azaC) on the morphological development of Candida albicans blastospores has been investigated by microscopic observations . It was found that this compound does not produce any morphogenetic effect when the cells are not induced to mycelial form . By contrast, on the induced cells, 5-azaC markedly accelerates the process of germ tube formation . In addition in the treated cells, yeast-mycelium conversion develops synchronously, whereas it is asynchronous and slow in the normal cells . These data indicate that, together with phenotypic modifications, modulation of gene activity by DNA demethylation occurs in Candida albicans during morphogenetic changes.

Acta Derm Venereol, 1988, 68(2), 98 - 101
In vitro adherence of Candida albicans to human corneocytes . Inhibition by chitin-soluble extract; Kahana M et al.; In vitro adherence of Candida albicans to human corneocytes and the effect of a chitin-soluble extract (CSE) on the adherence reaction were studied . Adherence of the yeasts to cells obtained from different individuals was variable . However, repeated adherence tests with pooled corneocytes of 2 individuals from this group showed that the adherence parameters did not differ greatly throughout these tests . CSE at the concentration of 50 mg/ml had a significant inhibitory effect on the attachment of C . albicans to the corneocytes, most probably by blocking their receptors of attachment . The data indicate that the preparation may be useful in the prophylactive management of recurrent cutaneous candidiasis in susceptible individuals.

Acta Derm Venereol, 1988, 68(2), 165 - 8
Racial differences in experimental skin infection with Candida albicans; Rebora A et al.; The forearm skin of 10 Caucasians and 10 American Negroes was inoculated with Candida albicans and the severity of the ensuing dermatitis as well as the population of Candida and other aerobes in the inoculum site have been assessed . Negroid skin proved to be less susceptible to irritation, even though it harboured a higher population of yeasts and aerobes other than Candida.

Klin Wochenschr, 1987 Dec 15, 65(24), 1169 - 72
Renal infarction with fatal bleeding--an unusual complication of Candida albicans endocarditis; Mugge A et al.; A patient with mitral valve endocarditis due to Candida albicans infection is presented . Because of persistent fever and one episode of transient right-sided hemiparesis, the patient underwent mitral valve replacement . Two weeks after successful valve replacement, the patient suddenly developed acute abdominal pain and died before a surgical intervention could be initiated . Autopsy examination revealed a renal infarction in the lower part of the right kidney with a large rupture of the capsule and retroperitoneal bleeding . A myocotic aneurysm could not be detected . The clinical significance of renal infarction in infective endocarditis is discussed.

J Immunol Methods, 1987 Dec 4, 105(1), 127 - 31
Measurement of antibodies to Candida albicans as a screening test for humoral immunodeficiency; Phillips DI et al.; In screening for defects in humoral immunity, as well as measuring serum immunoglobulins it is advisable to have some measure of antibody production, e.g., immunising with a test antigen and measuring the antibody response some days later . However, this delay may be inconvenient and requires a second blood sample . An alternative is to test for antibody to a widespread commensal organism to which the patient must have been repeatedly exposed . The measurement of antibody to E . coli by haemagglutination has been previously used for this purpose . We report here that an equally good and simpler alternative is to measure antibodies to the commensal Candida albicans by immunofluorescence . Using a polyvalent conjugate, all 114 blood donors tested had antibody titres greater than 8 to C . albicans; similar responses were noted in 20 children (aged 6 months-16 years) without recurrent infections . In contrast, anti-candida responses were low or absent as expected in patients with hypogammaglobulinaemia but also in some patients with other immunodeficiency diseases . Overall candida immunofluorescence closely paralleled E . coli haemagglutination.

J Allergy Clin Immunol, 1987 Dec, 80(6), 816 - 20
Allergic bronchopulmonary candidiasis: case report and suggested diagnostic criteria; Lee TM et al.; A patient with an illness consistent with allergic bronchopulmonary candidiasis is described . The patient had asthma, atelectatic pulmonary infiltrates on three occasions, immediate cutaneous reactivity as low as 10(-7) (wt/vol) to Candida albicans extract, and precipitating antibody to this organism . C . albicans was the only organism cultured from two bronchial lavage specimens . Total serum IgE was elevated to 5745 ng/ml and decreased rapidly with corticosteroid therapy . Serologic studies were not consistent with allergic bronchopulmonary aspergillosis . Serum IgE to C . albicans, measured by ELISA after adsorption of IgG from the serum samples by incubation with staphylococcal protein A, was found to be 575% to 650% above control values . The serum IgE antibody activity against Candida decreased with clinical improvement after corticosteroid therapy.

Infect Immun, 1987 Dec, 55(12), 3207 - 8
Ploidy and DNA content of Candida stellatoidea cells; Kwon-Chung KJ et al.; Three isolates of Candida stellatoidea contained approximately the same amount of DNA per blastospore (38.3 to 41.9 fg) as did a known diploid isolate of Candida albicans and about twice as much as did a haploid isolate of Saccharomyces cerevisiae . The diploidy of C . stellatoidea was supported by demonstration of mitotic segregation of an ade marker.

J Immunogenet, 1987 Dec, 14(6), 317 - 21
Murine candidiasis . III . Host inflammatory responses are regulated in part by class I MHC genes; Ashman RB; Host responses to experimental Candida albicans infection in mice have been shown previously to be regulated by genes in the major histocompatibility complex (MHC) . Results reported here show that at least part of this control can be mapped to class I MHC genes.

Pharm Res, 1987 Dec, 4(6), 495 - 8
In vivo efficacy of antifungal oxoaporphine alkaloids in experimental disseminated candidiasis; Clark AM et al.; The efficacy of three antifungal oxoaporphine alkaloids, liriodenine, liriodenine methiodide, and oxoglaucine methiodide, was determined in a mouse model of disseminated candidiasis . Mice infected with a lethal dose of Candida albicans NIH B311 were administered varying doses of each drug intraperitoneally or intravenously 7 hr postinfection . Reductions in the number of colony-forming units (CFU) recovered per milligram of kidney tissue were observed in drug-treated animals compared to vehicle-treated control mice . Significance was determined by the Wilcoxon nonparametric rank sum test . Intravenous administration of both liriodenine and liriodenine methiodide resulted in a significant reduction in the number of recovered CFU, while there was no significant response to treatment with oxoglaucine methiodide.

Eur J Clin Microbiol, 1987 Dec, 6(6), 657 - 8
Candida albicans endocarditis possibly related to systemic candidiasis in a heroin addict; Bisbe J et al.; A case of Candida albicans endocarditis is described which developed in a heroin addict with aortic valvulopathy after an episode of cutaneous and chondrocostal candidiasis related to the use of "brown" heroin . To our knowledge this is the first case reported in the English literature . This complication should be suspected in all heroin addicts with this new syndrome, especially if valvulopathy is present.

Antimicrob Agents Chemother, 1987 Dec, 31(12), 1901 - 3
Toxicity and therapeutic effects in mice of liposome-encapsulated nystatin for systemic fungal infections; Mehta RT et al.; The therapeutic activity of nystatin (NYS) incorporated in multilamellar liposomes (L-NYS) was studied in vivo . Hale-Stoner mice injected intravenously with various doses of L-NYS and free NYS showed a significant reduction in toxicity of NYS after the NYS was incorporated into liposomes (maximal tolerated doses, 16 and 4 mg/kg of body weight, respectively) . The maximal tolerated dose of free NYS had no effect in the treatment of mice infected with Candida albicans, whereas L-NYS at an equivalent dose improved the survival of mice . A marked increase in survival was observed when L-NYS was administered in higher and multiple doses (total doses up to 80 mg/kg) . Liposome encapsulation thus provided a means for intravenous administration of NYS, reducing its toxicity and making it an active systemic antifungal agent.

Antimicrob Agents Chemother, 1987 Dec, 31(12), 1897 - 900
Formulation, toxicity, and antifungal activity in vitro of liposome-encapsulated nystatin as therapeutic agent for systemic candidiasis; Mehta RT et al.; Multilamellar vesicles containing nystatin (NYS) were compared with vesicles containing the free drug for toxicity to erythrocytes and for antifungal activity in vitro . Liposomal nystatin was as active as free NYS was against a wide variety of yeasts and fungi . The antifungal activity against Candida albicans was maintained with different liposome compositions and without sterols . Liposome encapsulation also protected the erythrocytes from the toxicity of free NYS.

Acta Ophthalmol (Copenh), 1987 Dec, 65(6), 741 - 4
Endogenous candida endophthalmitis . Report of two cases; Haskjold E et al.; Two cases of endogenous endophthalmitis as a complication to spontaneous abortion, truly caused by candida albicans are presented . One patient received no antimycotic treatment . Endophthalmitis resulted in amaurosis in the affected eye, which had to be enucleated . The second patient was treated with intravenously administered amphotericin B and flucytocine, and was cured . The importance of early diagnosis and treatment is stressed.

Photodermatol, 1987 Dec, 4(6), 312 - 6
An adaptation of the Candida albicans phototoxicity test to demonstrate photosensitizer action spectra; Gibbs NK; The Candida albicans assay is widely used for the testing of potential photosensitizers, especially furocoumarins . A novel adaptation of this assay is described which provides a rapid, inexpensive and easy-to-perform method of producing action spectra . The use of filter paper rectangles with central apertures instead of the usual discs, and monochromatic irradiation with a liquid light guide reduces some of the problems associated with the standard assay . Action spectra for 8-methoxypsoralen and a new pyrrolocoumarin derivative are presented as illustrative examples.

Acta Pathol Microbiol Immunol Scand {C}, 1987 Dec, 95(6), 265 - 74
Degradation of IgA1, IgA2, and S-IgA by Candida and Torulopsis species; Reinholdt J et al.; Nine strains, isolated from leukoplakias or normal mucosa of the oral cavity, and representing the species Candida albicans, C.tropicalis, and Torulopsis glabrata were tested for the capacity to degrade IgA1, IgA2, and S-IgA in liquid cultures . IgA fragments were characterized by SDS-PAGE of culture supernatants in combination with immunoblotting analysis using antibodies specific for heavy chain and light chain determinants . Strains of C.albicans and C.tropicalis were found to express stronger proteolytic activity than a strain of T.glabrata . The three types of IgA were all degraded, alpha-chains being the primary targets . Immunoblotting analysis indicated that divalent fragments corresponding to the deletion of one or both of the Fc alpha constant domains (F(abc)2 alpha or F(ab)2 alpha) were produced . Monovalent half-molecules corresponding to these fragments could also be detected, suggesting that the yeast strains were capable of cleaving inter-alpha-chain disulphide bridges . The possible consequences of yeast-induced degradation for the function of IgA antibodies are discussed.

J Med Vet Mycol, 1987 Dec, 25(6), 355 - 63
Induction of protection against candidiasis in tumor-bearing mice by vaccination with Candida albicans ribosomes; Segal E et al.; The aim of this study was to determine whether vaccination of tumor-bearing mice with ribosomes of Candida albicans would result in the induction of protective immunity . Therefore, (BB)F1 mice were inoculated intraperitoneally with the thymoma, EL-4, then immunized with ribosomes purified from C . albicans, and challenged intravenously with C . albicans to assess the protective response . Unimmunized mice, both normal and tumor-bearing, treated in the same manner served as controls . Both normal and tumor-bearing mice developed protective immunity in response to immunization with ribosomes . The protected mice had fewer colony-forming units in their kidneys 3 days after intravenous challenge than the unimmunized control animals, regardless of tumor status . Moreover, all unimmunized mice, tumor-bearing and normal, developed delayed hypersensitivity to the ribosomes, as well as ribosome-specific antibody, both of which were of the same order of magnitude . Therefore, the EL-4 thymoma does not suppress the immune system of mice, and they are capable of responding immunologically in a normal manner to C . albicans.

J Clin Microbiol, 1987 Dec, 25(12), 2424 - 5
Umbelliferyl-labeled galactosaminide as an aid in identification of Candida albicans; Perry JL et al.; The initial evaluation of a fluorescence, nonmicroscopic method of rapid identification of Candida albicans is described . A total of 524 yeast isolates were evaluated in parallel by the umbelliferyl-conjugated N-acetyl-beta-D-galactosaminide (UAG) test and the germ tube (GT) test in comparison with the API 20C Yeast Identification System . The UAG test correctly identified 333 of the 334 isolates of C . albicans (99.7%), and the GT test identified 328 (98%) . There were three false-positive GT reactions and five false-positive UAG reactions with 69 isolates of C . tropicalis . The sensitivity and specificity were 99 and 97%, respectively, for the UAG test and were both 98% for the GT test . The UAG test requires less than 2 h for test completion compared with 2 to 4 h for the GT test, is similar in cost, has a nonmicroscopic visual endpoint, and eliminates the health hazards of handling pooled human sera.

Oral Surg Oral Med Oral Pathol, 1987 Dec, 64(6), 698 - 701
Influence of radiation therapy on oral Candida albicans colonization: a quantitative assessment; Rossie KM et al.; An increase in quantity of oral Candida albicans was documented in patients receiving head and neck radiation therapy during and after therapy, as assessed by an oral-rinse culturing technique . The amount of the increase was greater in denture wearers and directly related to increasing radiation dose and increasing volume of parotid gland included in the radiation portal . A significant number of patients who did not carry C . albicans prior to radiation therapy developed positive cultures by 1 month after radiation therapy . The percentage of patients receiving head and neck radiation therapy who carried C . albicans prior to radiation therapy did not differ significantly from matched dental patient controls.

J Med Microbiol, 1987 Dec, 24(4), 333 - 41
Mechanisms of association of Candida albicans with intestinal mucosa; Kennedy MJ et al.; The association of Candida albicans with gastrointestinal (GI) mucosal surfaces was studied in vitro and in vivo . The caecal mucosal surfaces from antibiotic-treated and untreated control mice challenged orally with C . albicans revealed that large numbers of C . albicans were associated with the intestinal epithelium of antibiotic-treated mice but not with that of the control mice that possessed an indigenous wall-associated bacterial flora . Moreover, Candida cells only penetrated deep into the mucosa of animals in which the ecology of the intestinal microflora had been disrupted . In mice given antibiotics, C . albicans was associated with the mucosa of all areas of the GI tract; the caecal mucosa had the most associated Candida, whereas the stomach and small intestine had very few associated yeasts . Further examination of caecal mucosa from antibiotic-treated mice showed that C . albicans associated with the mucosa by at least five distinct mechanisms . These included: adhesion to epithelium, adhesion to mucus, co-adhesion to adherent fungi, co-adhesion to adherent bacteria, and entrapment in the mucous gel overlying the epithelium . The cell-surface hydrophobicity of C . albicans also was examined and found not to play a role in Candida adhesion to intestinal mucosa . The predominant association mechanisms appeared to be entrapment in the mucous gel, and adhesion to mucus and the epithelium . The ecological and pathological significance of co-adhesion by C . albicans to attached organisms is unclear but it may be important in the initiation of mucosal lesions.

Dis Mon, 1987 Dec, 33(12), 681 - 780
Neutrophil function disorders; Boxer LA et al.; The polymorphonuclear leukocyte (neutrophil) is the most important phagocytic cell that defends the host against acute bacterial infection . Disorders of neutrophil function are suggested by recurrent cutaneous, periodontal, respiratory, or soft tissue infections . Staphylococcus aureus, gram-negative bacilli, and less commonly, Candida albicans, are the causative organisms . Treatment is supportive involving surgical drainage and antibiotics . Bone marrow transplantation offers hope to some patients . The biochemical and molecular defects have been identified for some of these disorders . Identification of these defects and their physiologic consequences have improved our understanding of how the activated neutrophil is attracted and adheres to inflammatory sites, and produces toxic products that destroy bacteria . However, the activated neutrophil may also damage normal tissue and participate in diseases such as rheumatoid arthritis and the adult respiratory distress syndrome (ARDS).

J Bacteriol, 1987 Dec, 169(12), 5579 - 88
Unique phenotype of opaque cells in the white-opaque transition of Candida albicans; Anderson JM et al.; Select strains of Candida albicans switch reversibly and at extremely high frequency between a white and an opaque colony-forming phenotype, which has been referred to as the white-opaque transition . Cells in the white phase exhibit a cellular phenotype indistinguishable from that of most standard strains of C . albicans, but cells in the opaque phase exhibit an unusually large, elongate cellular shape . In comparing the white and opaque cellular phenotypes, the following findings are demonstrated . (i) The surface of the cell wall of maturing opaque cells when viewed by scanning electron microscopy exhibits a unique pimpled, or punctate, pattern not observed in white cells or standard strains of C . albicans . (ii) The dynamics of actin localization which accompanies opaque-cell growth first follows the pattern of budding cells during early opaque-bud growth and then the pattern of hypha-forming cells during late opaque-bud growth . (iii) A hypha-specific cell surface antigen is also expressed on the surface of opaque budding cells . (iv) An opaque-specific surface antigen is distributed in a punctate pattern.

Clin Exp Immunol, 1987 Dec, 70(3), 520 - 8
Activation of pulmonary macrophages for fungicidal activity by gamma-interferon or lymphokines; Brummer E et al.; The ability of murine recombinant gamma interferon (IFN) or lymphokines to enhance the fungicidal activity of murine pulmonary macrophages (PuM) was studied in in vitro . PuM monolayers were incubated overnight with IFN, lymph node cells (LNC) plus concanavalin A, supernatants from Con A stimulated LNC or spleen cell cultures (Con A Sup), or tissue culture medium (TCM) +/- Con A (5 micrograms/ml) or +/- lipopolysaccharide (LPS, 10 ng to 10 micrograms/ml) . After treatment, culture fluids were removed and PuM were challenged for 4 h with the yeast-form Blastomyces dermatitidis or 2 h with Candida albicans . Inoculum colony forming units (CFU) of B . dermatitidis were significantly reduced by PuM treated with 1000 U/ml of IFN (25 +/- 3%), Con A Sup (25 +/- 3%) or LNC plus Con A (37-44%), but not by TCM, ConA or LPS . Candida albicans was killed by PuM treated with Con A Sup (33 +/- 8%) or LNC plus Con A (30-43%), but not by TCM, Con A, or LPS, and the activity of Con A Sup was neutralized by anti-IFN antibody . Candida albicans was not significantly killed by PuM treated with IFN doses ranging from 1 to 10(5) U/ml; nor did addition of LPS to IFN, or prolonged (3 day) treatment with IFN, result in significant killing of C . albicans by PuM . However, IFN (100 U/ml) could activate resident peritoneal macrophages for significant candidacidal activity (63%) . These data indicate that PuM can be activated for fungicidal activity, and that PuM differ from resident peritoneal macrophages with regard to induction of candidacidal activity by recombinant gamma-IFN.

J Med Vet Mycol, 1987 Dec, 25(6), 403 - 13
The effects of azole and polyene antifungals on the plasma membrane enzymes of Candida albicans; Surarit R et al.; The two clinically important classes of antimycotic drugs, the polyenes and azoles, act on the plasma membrane of the cell . The primary modes of action are believed to be through interaction with sterols (polyenes) and alteration in sterol composition of the membrane (azoles) . In this report we show that, at growth inhibitory concentrations, the polyenes (nystatin and amphotericin) and azoles (miconazole and ketoconazole) also inhibit plasma membrane enzymes . There was extensive (greater than 75%) inhibition of the Candida albicans plasma membrane enzymes ATPase, glucan synthase, adenyl cyclase and 5'-nucleotidase, when assayed in situ . The antifungals papulacandin and echinocandin, which inhibit glucan synthesis, also inhibited plasma membrane enzymes in situ; glucan synthase (greater than 90%), 5'-nucleotidase (greater than 80%) and ATPase (70-80%) . Purified plasma membrane was prepared from yeast cells of C . albicans by two different techniques: concanavalin A stabilization and coating of spheroplasts with silica microbeads . In the purified plasma membrane vesicles prepared from concanavalin A the adenyl cyclase and phosphodiesterase were extensively (greater than 90%) inhibited by the three different classes of antifungal drugs; variable inhibition was observed with ATPase (70-100%) . The 3',5'-cyclic phosphodiesterase of the plasma membrane purified by the microbeads method was almost completely inhibited by all of the antifungals tested and there was partial inhibition of ATPase (20-85%) and adenyl cyclase (30-90%).

Pediatrics, 1987 Dec, 80(6), 876 - 9
Myeloperoxidase deficiency with extensive candidal osteomyelitis of the base of the skull; Weber ML et al.; A 6-year-old girl had a 7-month history of headaches and painful torticollis . A CT scan of the mastoids showed extensive bone destruction of the base of the skull and C-1 . Biopsies of the retropharyngeal area and of the anterior aspect of C-1 were performed: histopathologic findings were suggestive of mycotic infection and cultures were positive for Candida albicans . The child was treated successfully with amphotericin B . The immunologic evaluation demonstrated the absence of myeloperoxidase in the neutrophils.

Ann Intern Med, 1987 Nov, 107(5), 675 - 7
Antigen-specific T-cell anergy in progressive Mycobacterium marinum infection in humans; Dattwyler RJ et al.; The cellular immune responses of 12 patients with culture-proved Mycobacterium marinum infection involving deep tissues were studied . Of the 12 patients, 11 failed to respond to M . marinum antigens . All of the patients had, however, normal blastogenic responses to concanavalin A, phytohemagglutinin, pokeweed mitogen, and the antigens tetanus toxoid and Candida albicans . In contrast, 9 of 14 healthy fishermen responded to the M . marinum antigens with significant in-vitro blastogenesis . Infection of deep tissues with M . marinum is associated with antigen-specific T-cell anergy to M . marinum antigens.

Infection, 1987 Nov-Dec, 15(6), 417 - 21
Serial study of C-reactive protein during fungal esophagitis and enterocolitis; Kostiala I et al.; C-reactive protein (CRP) responses were followed in weekly serum samples in the course of eight episodes of esophagitis (37 sera) and ten episodes of enterocolitis (45 sera) caused by Candida albicans in an equal number of patients with hematologic malignancies under antibacterial medication . During fungal esophagitis CRP was elevated, with peak values ranging from 73 to 380 mg/l (mean +/- SD: 170 +/- 104 mg/l) . The same was true for fungal enterocolitis, with the peak values ranging from 54 to 225 mg/l (mean +/- SD: 146 +/- 56 mg/l) . In both these conditions, antimycotic treatment was followed by clinical improvement, reduced or eliminated fungal growth and falling levels of CRP, occasionally down to the normal value (less than 6 mg/l) . Thus, follow-up of CRP level is useful as an aid in the diagnosis of gastrointestinal candidosis and in evaluating its treatment.

Am J Vet Res, 1987 Nov, 48(11), 1658 - 61
Photosensitization of cattle in southeast Texas: identification of phototoxic activity associated with Cooperia pedunculata; Rowe LD et al.; A microbiological assay (Candida albicans) was used to screen plants in southeast Texas where bovine photosensitization (PS) of unknown cause was a recurring problem . Phototoxic activity was identified associated with dead leaf tips of Cooperia pedunculata, a native, perennial forb of the Amaryllis family (Amaryllidaceae) from central, southeast, and south Texas and parts of Mexico . A syndrome compatible with naturally occurring PS in cattle was induced in laboratory mice after oral administration of dead leaf material from C pedunculata . Availability and phototoxic activity of dead leaf material of C pedunculata corresponded with occurrence of PS in cattle . Seemingly, C pedunculata was involved in recurring PS.

J Gen Microbiol, 1987 Nov, 133 ( Pt 11), 3219 - 28
Proline-induced germ-tube formation in Candida albicans: role of proline uptake and nitrogen metabolism; Holmes AR et al.; Proline-induced germ-tube formation and cell-cell aggregation in four strains of Candida albicans were completely inhibited when the pH of the medium was 5.0 or lower, whereas morphogenesis induced by N-acetylglucosamine (GlcNAc) was unaffected even at pH 4.5 . The pH sensitivity of proline-induced germ-tube formation was not caused by a modulation of proline uptake, which was unchanged over the pH range 4.5-6.5 . The proline uptake system was specific, constitutive and subject to ammonium repression, and only one permease was detected, with a Km of 179 microM . Cultures deprived of nitrogen in the presence of glucose were derepressed for proline uptake but the yeast-mycelial transition could not be mediated by either proline or GlcNAc . The inhibition of morphogenesis was reversed when the nitrogen starvation was relieved by the addition of ammonium ions, proline, or certain amino acids . These results indicate that the nitrogen status of the cells is critical for the morphogenesis of C . albicans.

Antimicrob Agents Chemother, 1987 Nov, 31(11), 1756 - 60
Comparative in vitro and in vivo evaluation of N-D-ornithyl amphotericin B methyl ester, amphotericin B methyl ester, and amphotericin B; Parmegiani RM et al.; N-D-Ornithyl amphotericin B methyl ester (O-AME), a semisynthetic derivative of amphotericin B methyl ester (AME), was compared with amphotericin B (AMB) and AME . In vitro, O-AME was more active than the other two against Candida spp . and other fungi and was only slightly affected by inoculum size, addition of serum, or changes in pH . In vivo, the dose of O-AME required to produce a 10,000-fold reduction of Candida albicans in a mouse kidney infection was similar to that of AMB and 1/10 that of AME . After intravenous treatment of infected mice and rats and subcutaneous treatment of mice, average 50% protective doses for O-AME and AMB were similar . Acute intravenous 50% lethal doses in mice indicated that O-AME was one-ninth as toxic as AMB but twice as toxic as AME . Acute renal function tests in rats indicated that Sch 28191 was less than 1/10 as toxic as AMB and slightly more toxic than AME . On this basis, the calculated advantage relative to AMB (with AMB equal to 1) was 8 for O-AME and 1.5 for AME.

Zh Mikrobiol Epidemiol Immunobiol, 1987 Nov, (11), 63 - 8
{Immune system function in candidiasis patients}; Karaev ZO et al.; To compare the clinical picture and the immunological characteristics, 58 candidiasis patients differing by the severity and dissemination of the disease were examined . Chronic candidiasis of the skin and mucous membranes, the most severe and disseminated form of the disease, is associated with a decrease in the number of T-lymphocytes and changes in their subpopulations, as well as high titers of Candida albicans antigen and antibodies to it in blood sera . The immune system of patients with visceral candidiasis and chronic vulvovaginal candidiasis was similar to that of healthy persons in the characteristics under study . Immediate and mixed hypersensitivity occurred in candidiasis patients more frequently than in healthy persons . In extremely severe forms of Candida infection immediate hypersensitivity prevailed.

Clin Exp Immunol, 1987 Nov, 70(2), 316 - 21
Immunoglobulin A1 and A2 subclass of salivary antibodies to Candida albicans in patients with oral candidosis; Jeganathan S et al.; Immunoglobulin A antibody titres to a cytoplasmic protein extract of Candida albicans were determined by ELISA in saliva from 20 patients with oral candidosis and 21 controls . Patients had significantly increased levels of salivary IgA anti-Candida antibodies when compared with controls (P less than 0.001) . Antibody levels were associated with IgA1 subclass in 90% of the patients; in contrast, IgA2 subclass was predominant in 67% of the controls . Antifungal therapy resulted in significantly decreased IgA1 titres (P less than 0.05) whilst the mean IgA2 antibody titre remained unchanged . The results indicate that Candida infection may change the subclass pattern of salivary IgA antibodies.

Infect Immun, 1987 Nov, 55(11), 2783 - 8
Cytosolic calcium changes in individual neutrophils stimulated by opsonized and unopsonized Candida albicans hyphae; Levitz SM et al.; Previous experiments suggest the critical central role of the neutrophil (PMN) respiratory burst in the prevention and containment of disseminated candidiasis . A rise in cytosolic free calcium concentrations ({Ca2+}i) has been documented as an early event after PMN stimulation which is involved in the subsequent genesis of microbicidal and inflammatory respiratory burst products . {Ca2+}i were therefore determined in individual PMN, loaded with the fluorescent calcium probe fura-2 as they attached to and spread over serum-opsonized or unopsonized Candida albicans hyphae, particles that are too big to be completely ingested . After contact between hyphae and PMN, the PMN rapidly spread over hyphal surfaces . Although both opsonized and unopsonized hyphae stimulated similar magnitudes of peak median increases in PMN {Ca2+}i, the kinetics of responses differed; median {Ca2+}i peaked within 1 min after contact with opsonized hyphae versus 4 min after contact with unopsonized hyphae . Moreover, a detectable calcium transient did not invariably follow contact and spreading of each individual PMN over a hyphal surface . In contrast to patterns seen after stimulation of PMN with opsonized zymosan, in which {Ca2+}i is greatest in the periphagosomal region, there was a more uniform distribution throughout the cytoplasm in PMN stimulated with the noningestable hyphae . These alterations in the early patterns and timing of PMN stimulation may reflect analogous differences in subsequent events which control the efficiency and specificity of microbicidal responses to uningestible hyphae and which also determine whether host tissues are damaged by the generation of toxic PMN activation products.

Infect Immun, 1987 Nov, 55(11), 2619 - 24
Enhancement of non-Candida antibody responses by Candida albicans cell wall glycoprotein; Domer JE et al.; Two cell wall glycoprotein extracts from Candida albicans (glycoprotein {GP} and peptidoglucomannan {PGM}) were tested for their influence on antibody responses to type III pneumococcal polysaccharide and sheep erythrocytes . GP was isolated from lipid-extracted cell walls with ethylenediamine, whereas PGM was extracted with dilute sodium hydroxide . Both glycoproteins increased the number of antibody-producing plaque-forming cells in the spleens of mice immunized with type III polysaccharide or sheep erythrocytes, although PGM appeared to be about 10 times more effective . PGM could be administered up to 3 days prior to immunization with sheep erythrocytes to elicit enhancement; it did not have to be administered by the same route as the immunogen to cause significant enhancement . Enhancement did not appear to be the result of a direct mitogenic effect of GP and PGM on lymphocytes, nor did these glycoproteins appear to stimulate the production of B-cell growth factors or interleukin 2.

J Infect Dis, 1987 Nov, 156(5), 777 - 83
Evidence for a correlation between proteinase secretion and vulvovaginal candidosis; Cassone A et al.; Candida albicans isolates from nondiabetic, nonpregnant outpatients with vaginitis were compared for in vitro proteinase secretion with isolates from women without specific candidal vaginitis symptomatology (carriers) . Proteinase production was assayed in medium containing bovine hemoglobin (BH-P; 39 isolates in 69 independent determinations) or bovine serum albumin (BSA-P; 39 isolates in a single determination each) . All isolates had measurable, consistent BH-P secretion, and most also showed detectable BSA-P activity . However, isolates from patients were more proteolytic than those from carriers, with the difference being statistically highly significant . When the patients with vaginitis were categorized according to signs and symptoms, the highest BH-P values were recorded for those with full symptomatology, whereas the only BSA-P-negative isolates were from the group without vaginitis . Isolates from the patient and carrier groups did not differ as a whole in their growth potential in vitro, and all were germ tube responders in serum, independent of their source.

Cell Immunol, 1987 Nov, 110(1), 176 - 82
Effect of a local immune reaction on peripheral blood polymorphonuclear neutrophil microbicidal function: studies with fungal targets; Morrison CJ et al.; Peripheral blood polymorphonuclear neutrophils (PMN) from mice immunized with Blastomyces dermatitidis and then stimulated locally (intraperitoneally, ip) with B . dermatitidis antigen had enhanced killing of B . dermatitidis in vitro (54.4 +/- 19.49 of inoculum) compared to nonimmune mice (32.7 +/- 8.7%; P less than 0.02), nonimmune mice given antigen ip (30.6 +/- 14.0%; P less than 0.05), or immune mice not given antigen ip (15.4 +/- 9.9%; P less than 0.01) . Peripheral blood PMN from all four groups had marked killing ability against Candida albicans (91.8-99.3% of inoculum) . That the killing of B . dermatitidis was due to PMNs was demonstrated by lack of killing by isolated peripheral blood mononuclear cells from all four groups . A local immune reaction can result in enhancement of PMN fungicidal activity, and this is reflected even in peripheral blood PMN . We hypothesize this is an important component of normal host defenses against fungal infection, and likely other microbial infections . Enhancement of PMN microbicidal function by the soluble mediators presumed to be responsible for the effects observed may be an approach to immunomodulating therapy or prophylaxis of infection.

J Infect Dis, 1987 Nov, 156(5), 770 - 6
Unopsonized Candida albicans hyphae stimulate a neutrophil respiratory burst and a cytosolic calcium flux without membrane depolarization; Lyman CA et al.; We have defined major differences between events elicited during activation of human neutrophils by opsonized Candida hyphae (noningestible) or zymosan (ingestible) and by unopsonized Candida hyphae (also noningestible) . In response to opsonized particles, a transient increase in cytosolic free calcium was initially observed, followed by depolarization in the transmembrane potential and a respiratory burst . Without opsonins, zymosan did not elicit a response from neutrophils . In contrast, unopsonized Candida hyphae elicited a transient increase in cytosolic calcium, as well as triggered a respiratory burst; they did not, however, elicit a depolarization of the neutrophil membrane . Furthermore, the rate of superoxide generation decreased after a prolonged lag period . The calcium flux was also delayed and coincided with the onset of superoxide generation . Thus, our data demonstrate that Candida albicans hyphae activate neutrophils in the absence of added serum components and initiate a neutrophil respiratory burst without an antecedent membrane depolarization.

J Immunol, 1987 Oct 15, 139(8), 2761 - 7
Regulation of human polymorphonuclear neutrophil (PMN) activity against Candida albicans by large granular lymphocytes via release of a PMN-activating factor; Djeu JY et al.; Using a 24-hr radiolabel microassay developed in our laboratory that measures {3H}glucose uptake in residual Candida, we have identified the effector cells responsible for in vitro inhibition of Candida albicans growth as mainly polymorphonuclear neutrophils (PMN) and monocytes within the human peripheral blood cells . Highly purified T cells and large granular lymphocytes (LGL) that mediate natural killer activity which were obtained by Percoll density gradient centrifugation were found to have no innate activity against C . albicans . The LGL could not be activated by interferon-alpha, interferon-gamma or interleukin 2 to inhibit Candida growth although their K562 tumor cytotoxic activity was readily enhanced by these cytokines . Stimulation with heat-killed C . albicans also did not activate fungal growth inhibitory function in LGL and the supernatant of these activated LGL had no direct fungicidal activity . However, the activated LGL supernatant had the capability to enhance PMN function against C . albicans growth . Addition of recombinant human tumor necrosis factor, affinity-purified interferon-alpha, or interferon-gamma to PMN caused increased antifungal activity in PMN . However, antibodies to these cytokines had only a partial adverse effect on the ability of the activated LGL supernatant to stimulate PMN anti-Candida function . Therefore, the activated LGL supernatant appeared to contain a potent stimulator of PMN function which is as yet unidentified . These data indicate that LGL did not directly mediate anti-Candida activity but could indirectly influence C . albicans growth by activating PMN against the fungi through the release of a specific PMN-activating factor . Our findings therefore add another role to LGL which is the regulation of PMN function, the consequence of which is regulation of fungal immunity.

Antimicrob Agents Chemother, 1987 Oct, 31(10), 1558 - 61
Activity of terbinafine in experimental fungal infections of laboratory animals; Petranyi G et al.; The allylamine derivative terbinafine is the first antifungal agent with primary fungicidal properties against dermatophytes which acts systemically after oral application as well as locally after topical application . Comparative oral studies carried out with griseofulvin and ketoconazole in model infections such as guinea pig trichophytosis and microsporosis revealed terbinafine to be superior to the reference compounds both clinically and mycologically . An excellent antimycotic activity of terbinafine was also demonstrable after topical treatment of guinea pig dermatophytoses caused by Trichophyton mentagrophytes or Microsporum canis . Results of comparative chemotherapeutic studies carried out with econazole and tolnaftate demonstrated superior efficacy of terbinafine in the treatment of both trichophytosis and microsporosis . Skin infections of guinea pigs caused by Candida albicans and vaginal candidiasis in rats proved to be responsive to a topical application of terbinafine also . However, the reference compounds, clotrimazole and miconazole, exhibited activity superior to that of terbinafine in both models.

J Gen Microbiol, 1987 Oct, 133 ( Pt 10), 2817 - 24
Segregation of proteinase-negative mutants from heterozygous Candida albicans; Crandall M et al.; The extracellular acidic proteinase (EC 3.4.23.6) produced by Candida albicans has been reported to be a virulence factor . In studying the role of this proteinase in human disease, we determined the optimum conditions for stimulating proteinase production in order to isolate proteinase-negative (Prt-) mutants . We found that in liquid medium containing bovine serum albumin (BSA) as the sole nitrogen source, at pH 4 and 27 degrees C, the sensitivity of proteinase detection was considerably greater than when assayed on BSA agar at 37 degrees C . This observation is due, in part, to temperature sensitivity of proteinase induction . Nitrogen starvation did not induce proteinase . Proteinase production on agar was increased by adding 0.01% yeast extract (YE) to BSA medium . Using BSA + YE agar to isolate mutants, it was discovered that C . albicans ATCC 28366 was heterozygous for a Prt- mutation . Spontaneous Prt- mutants occurred at a frequency of 2 x 10(-3) . Ultraviolet light increased the mitotic segregation of Prt- cells to a frequency of 1 x 10(-2) . The Prt- phenotype showed a large inoculum effect, Prt- segregants reverted with a high frequency, and the revertants were unstable.

Zentralbl Bakteriol Mikrobiol Hyg {A}, 1987 Oct, 266(3-4), 491 - 6
Hydrophobicity of Candida albicans related to their adherence to mucosal epithelial cells; Macura AB; A total of 150 Candida albicans strains were examined, using a salt aggregation test (SAT) and an improved salt aggregation test (ISAT) . The fungal strains were isolated from patients or taken from a collection . Out of 150 strains, 20.7% were autoaggregating in the ISAT . In the SAT, 12% of the strains were autoaggregating in saline and 14% in phosphate buffer . The remaining strains did not clump . Pretreatment of the autoaggregating strains with detergents (Tween 80 and ethylene glycol) prevented aggregation in some of them . The adherence capacity to buccal epithelial cells of the fungal strains autoaggregating in the SAT and ISAT, was compared to that of the nonaggregating ones . The autoaggregating strains revealed significantly higher adherence values (p less than 0.002) . The adherence ability to buccal epithelial cells of the autoaggregating strains before and after their pretreatment with detergents was compared . The adherence values after pretreatment were significantly lower (p less than 0.001).

J Med Vet Mycol, 1987 Oct, 25(5), 335 - 8
Adhesion of Candida albicans to buccal epithelial cells exposed to chlorhexidine gluconate; Tobgi RS et al.; The adhesion of Candida albicans to buccal epithelial cells (BEC) exposed to chlorhexidine gluconate either in vivo or in vitro, was studied using BEC obtained from an adult and two children . There was a significant reduction in the adherence of yeasts to BEC collected immediately after an oral rinse of chlorhexidine . Also a significant positive correlation was noted (r = 0.99) between the time which elapsed after a chlorhexidine rinse and yeast adhesion to BEC . In-vitro exposure of BEC from both children and the adult to 0.2%, 0.02%, and 0.002% chlorhexidine, also reduced candidal adhesion to BEC.

J Med Vet Mycol, 1987 Oct, 25(5), 329 - 33
Inhibition of 14 alpha-sterol demethylase activity in Candida albicans Darlington does not correlate with resistance to azole; Hitchcock CA et al.; The 14 alpha-sterol demethylase in the azole-resistant Candida albicans, strain Darlington, is less sensitive to the triazole ICI 153066 than are two azole-sensitive strains, A and B . However, there is no direct correlation between the IC50 values for triazole inhibition of the demethylase and IC50 values for growth . It appears that the basis of azole resistance in strain Darlington may not be explained solely on the basis of a lack of sensitivity of its 14 alpha-sterol demethylase enzyme, but that other target sites for azole may be altered or absent.

J Med Vet Mycol, 1987 Oct, 25(5), 307 - 18
Aspects of the effect of bile salts on Candida albicans; Marshall SE et al.; Cholic acid, chenodeoxycholic acid, deoxycholic acid, glycocholic acid, glycodeoxycholic acid, hyodeoxycholic acid and lithocholic acid as their sodium salts, were fungistatic to the growth of Candida albicans . Of the compounds tested, cholic acid, deoxycholic acid and chenodeoxycholic acid were the most active . In combination with other antifungal agents only cholic acid exhibited synergism with amphotericin B, whilst the imidazole antifungal agents inhibited the action of the bile salts . The bile salt minimal inhibitory concentrations were close to the critical micelle concentrations . Even though the compounds are surface active they did not cause loss of intracellular K+ and were without effect on oxygen consumption . The bile salts, particularly cholic acid, produced morphological changes that gave rise to swollen cells.

Mycopathologia, 1987 Oct, 100(1), 7 - 15
Growth of Candida albicans in a minimal synthetic medium without biotin; Vidotto V et al.; Growth of Candida albicans strain B 311-10 was observed in a minimal synthetic biotin-free medium, using different glucose concentrations, during the first 30 hours of its development at 28 degrees C . The yeast's growth was observed spectrophotometrically at 675 nm reading its optical density every hour . The minimal medium of Shepherd et al., with glucose (15 g/L) and biotin was modified: this vitamin was eliminated and the concentration of glucose was gradually lowered to 0.5 g/L . At 5 g/L of glucose and without biotin very good growth was obtained . Based on our results during the first 30 hours of growth, biotin has no influence on the yeast's growth . This medium would be useful for the study of the physiology of C . albicans during the first period of its development.

Mycopathologia, 1987 Oct, 100(1), 27 - 35
Action of chlorhexidine on budding Candida albicans: scanning and transmission electron microscopic study; Bobichon H et al.; Chlorhexidine is widely used as a bacterial drug whose method of action has been well described in bacteria . Its fungicidal properties have been proved . We show here the effects of a sublethal dose of a preparation of digluconate of chlorhexidine on budding Candida albicans . A fungistatic action is revealed by a decrease in the percentage of budding cells, and two main types of alterations can be observed with transmission electron microscopy (T.E.M.): a loss of cytoplasmic components and a coagulation of nucleoproteins . With scanning electron microscopy (S.E.M.), the cell walls show morphological modifications.

J Clin Pathol, 1987 Oct, 40(10), 1159 - 61
Use of modified resistogram to type Candida albicans isolated from cases of vaginitis and from faeces in the same geographical area; Hunter PR et al.; Ninety strains of Candida albicans were isolated from vaginal swabs taken by general practitioners from cases of vaginal candidosis . One hundred and nine strains were also isolated from 300 specimens of faeces received from outpatients living in the same geographical area . These strains were typed using a modification of the resistotyping method . We were unable to find any significant differences between the two populations of strains . This suggests that no particular resistotype has an increased ability to cause vaginitis.

J Antimicrob Chemother, 1987 Oct, 20(4), 529 - 35
Effect of beta-lactams and aminoglycosides on human polymorphonuclear leucocytes; Burgaleta C et al.; The effects of four beta-lactams (cefotaxime, cefoxitin, ceftazidime and latamoxef) and three aminoglycosides (amikacin, sisomicin and tobramycin) on human polymorphonuclear (PMN) leucocytes were examined . Chemotaxis was studied by agarose migration and in a Boyden chamber . Agarose migration of PMN leucocytes was not affected significantly by ceftazidime and latamoxef (25-200 mg/l) . However cefoxitin (50-200 mg/l) decreased agarose migration to 52-65% of the control values, and cefotaxime (25-200 mg/l) reduced migration to 29-67% of control values . The Boyden chamber method showed no significant inhibition of chemotaxis by any of the antibiotics tested . None of these antibiotics affected phagocytosis or killing of Candida albicans by human PMNs.

Epidemiol Infect, 1987 Oct, 99(2), 421 - 8
Strain differentiation of Candida albicans by morphotyping; Phongpaichit S et al.; Strains of Candida albicans can be differentiated by the morphological features of streak colonies developed on malt agar . A morphotyping system is proposed, where numerical codes are assigned primarily on the basis of the nature and extent of marginal fringing and the surface topography of the streak colony . The system allows ready differentiation to be made of morphotypes, requires no specialized equipment or expertise and provides a simple and reproducible means for epidemiological studies of candida and candidosis.

Clin Chem, 1987 Oct, 33(10), 1925 - 8
Participation of peptide moieties in adhesive behavior of antigenic mannans of Candida albicans to the plastic microtiter plate in enzyme-linked immunosorbent assay; Tojo M et al.; We report our studies of the mechanism of the adhesion of mannans of Candida albicans NIH A-207 and C . albicans NIH B-792 strains to the surface of a polystyrene microtiter plate being utilized for enzyme-linked immunosorbent assay (EIA) of antigens of this pathogenic yeast species . This binding was manifested predominantly by the peptide moieties of the mannans forming hydrophobic bonds with the plastic molecule . Eliminating the peptide of each mannan by treating it with a hot aqueous alkaline solution of NaBH4 also eliminated color development in the EIA.

J Med Chem, 1987 Oct, 30(10), 1715 - 9
Synthesis and biological properties of N3-(4-methoxyfumaroyl)-L-2,3-diaminopropanoic acid dipeptides, a novel group of antimicrobial agents; Andruszkiewicz R et al.; A series of dipeptides with N3-(4-methoxyfumaroyl)-L-2,3-diaminopropanoic acid (FMDP), the irreversible inhibitor of glucosamine-6-phosphate synthetase from bacteria and fungi, have been synthesized and their antibacterial and antifungal properties in vitro evaluated . The results demonstrate that these peptides inhibit the growth of a number of the tested microorganisms, especially pathogenic fungus Candida albicans . The results of competitive antagonism studies indicate specific peptide transport of the peptides via peptide permeases as drug delivery system and gives evidence for the high selectivity of the action upon the cells, as a result of the inhibition of generation of glucosamine.

J Infect Dis, 1987 Oct, 156(4), 561 - 6
An enzyme-linked immunosorbent assay for quantifying adherence of Candida to human vascular endothelium; Filler SG et al.; Success in elucidating the pathogenesis of certain bacterial infections through studies of bacterial adherence to host cells has stimulated interest in parallel investigations of fungal adherence . Fungal adherence differs from bacterial adherence, especially when fungal coadherence (adherence of fungal cells to each other) is a factor . Using human umbilical vein endothelial cells cultured in a living monolayer in microtiter plates, we developed an ELISA to study adherence of Candida albicans to endothelial cells in the absence of yeast coadherence . A rabbit antibody to Candida detected the adherent Candida, and an alkaline phosphatase-conjugated antibody to rabbit IgG was the developing antibody . A linear relationship between the log of the optical density and the log of the number of adherent organisms was seen for wells containing 3 X 10(4)-1 X 10(6) organisms (r = .923- .965) . In addition to measuring adherence of living Candida to living target cells and avoiding Candida coadherence, this assay makes it possible to investigate adherence limited to lumenal surfaces, conserves reagents, and facilitates the testing of large numbers of potential adherence modifiers.

Mycopathologia, 1987 Oct, 100(1), 43 - 8
The effect of the supernatants obtained from Sporothrix schenkii and Candida albicans culture on the generation of reactive oxygen species by polymorphonuclear leukocytes; Yoshioka A et al.; The effect of the supernatants obtained from the liquid culture medium of Sporothrix schenkii and Candida albicans on the generation of superoxide anion (O2- and hydroxyl radicals OH., the elements of reactive oxygen species (ROS), and chemoluminescence (CL), a measure of several ROS, by polymorphonuclear leukocytes (PMNs) was examined . In our study, it was shown that the supernatant of S . schenkii increased all types of ROS generation examined and CL, while that of C . albicans increased OH . generation and CL . The effect of the supernatants of S . schenkii on OH . generation and CL and that of C . albicans on CL were most remarkable when the supernatant obtained 8 weeks after the inoculation was used . The supernatant of S . schenkii was shown to be a much more potent stimulant than the supernatant of C . albicans . This ROS-stimulating effect of the supernatant of S . schenkii was heat stable but not dialyzable . These findings suggest the possible role of ROS produced by infiltrated PMNs in the inflammatory skin lesions induced by S . schenkii.

J Med Vet Mycol, 1987 Oct, 25(5), 283 - 90
Candidacidal activity of macrophages from three mouse strains as demonstrated by a new method: neutral red staining; Kolotila MP et al.; A new method for assessing the candidacidal activity of macrophages utilizing neutral red stain gave results comparable to well established vital staining methods, methylene blue and acridine orange, and to the absence of germ tube formation of Candida albicans . Dead yeast cells are uniformly stained red while viable yeast cells are unstained except for a red stained vacuole . This assay was used to demonstrate the difference in candidacidal activity between resident and in vivo stimulated peritoneal macrophages of CBA/J, BALB/c and CFW mice . Stimulation of peritoneal macrophages with Concanavalin A in vivo resulted in a significant increase in candidacidal activity in the macrophages from male and female mice . In addition, Concanavalin A-elicited macrophages from female BALB/c and CFW mice exhibited greater candidacidal activity than macrophages from male BALB/c and CFW mice whereas Concanavalin A-elicited macrophages from CBA/J male and female mice exhibited a similar candidacidal ability . Resident peritoneal macrophages from male mice were significantly less candidacidal than were macrophages from female mice with the exception of the macrophages from male CBA/J mice which were as active as the macrophages from female mice.

JAMA, 1987 Sep 18, 258(11), 1505 - 8
In vivo diagnostic testing and immunotherapy for allergy . Report I, Part II, of the Allergy Panel . Council on Scientific Affairs; Characterization of a cytochrome P450 deficient mutant of Candida albicans; A previously described Candida albicans nystatin resistant mutant blocked in 14 alpha-demethylation of lanosterol was shown to also lack all traces of cytochrome P450 as determined by carbon monoxide difference spectra . This strain does not require ergosterol for growth and reverted to an ergosterol producing, cytochrome P450 containing strain indicating no other lesions . Cytochrome P450 mutants described in Saccharomyces cerevisiae are auxotrophic for ergosterol or contain a second mutation in 5,6 desaturation of the sterol B ring . These results suggest that a cytochrome P450 lesion in these yeasts have different phenotypes and may reflect different sterol requirements for the two organisms.

Jpn J Antibiot, 1987 Sep, 40(9), 1644 - 50
{Evaluation of oral amphotericin B with serial measurement of the serum concentration in patients with leukemia and related disorders}; Okuda T et al.; A total of 10 episodes in 7 patients with leukemia or related disorders was treated with oral amphotericin B (AMPH) . In 8 episodes AMPH were used prophylactically for severe neutropenia, and in the remaining 2 it was given when the patients were feverish . A daily dose of 2,400 mg of AMPH was given orally once a day and serum concentrations of AMPH were determined serially with bioassay . Two hours after administration, the mean serum concentration of AMPH rose to 0.15 microgram/ml, and reached 0.27 microgram/ml after 24 hours . The concentration was maintained between 0.23 microgram/ml and 0.39 microgram/ml through the following 7 days . These concentrations exceed the minimal inhibitory concentrations of most strains of Candida albicans . In 8 occasions of prophylactic use, no fungal infection was encountered . In a patient with pneumonia, chest X-ray and physical findings improved with administration of oral AMPH . Side effect of AMPH was seen in 1 patient, which was mild proteinuria and was eased rapidly after the withdrawal of AMPH . Clinical laboratory tests showed 1 case of proteinuria and disorder of kidney but did not clear under influence of AMPH . These results suggest that oral administration of AMPH is clinically and therapeutically effective and relatively safe for the prophylaxis or the treatment of fungal infection in patients with leukemia or related disorders.

Klin Monatsbl Augenheilkd, 1987 Sep, 191(3), 222 - 5
{Effect of corticosteroids in antimycotic therapy of Candida keratitis}; Behrens-Baumann W et al.; The effect of corticosteroid treatment in addition to antimycotic therapy was studied on the basis of a newly developed keratomycosis model . Forty-eight hours after intracorneal injection of a defined strain of Candida albicans, Amphotericin B drops were administered at one-hour intervals ten times a day . To improve penetration of the drops abrasion of the corneal epithelium was performed every three days . In addition, 4 mg of dexamethasone phosphate was injected subconjunctivally into one eye every two days . The results showed that in this low dosage dexamethasone did not worsen the course of the infection in a single case . On the contrary, there was significantly less neovascularization (p less than 0.05) than in the group not treated with dexamethasone . It therefore appears that combination thereby is the best form of treatment for keratomycosis; this is also supported by clinical observations.

Antimicrob Agents Chemother, 1987 Sep, 31(9), 1365 - 8
Antifungal activity of the allylamine derivative terbinafine in vitro; Petranyi G et al.; Terbinafine, an allylamine derivative, represents the most effective of this new chemical class of antimycotic compounds . Under in vitro conditions, terbinafine proved to be highly active against dermatophytes (MIC range, 0.001 to 0.01 microgram/ml), aspergilli (MIC range, 0.05 to 1.56 micrograms/ml), and Sporothrix schenckii (MIC range, 0.1 to 0.4 microgram/ml) and also exerted good activity against yeasts (MIC range, 0.1 to greater than 100 micrograms/ml) . The growth of Malassezia furfur was inhibited also (MIC range, 0.2 to 0.8 microgram/ml) . Terbinafine displays a primary fungicidal action against dermatophytes, other filamentous fungi, and S . schenckii . The type of action against yeasts is species dependent and can be primarily fungicidal (Candida parapsilosis) or fungistatic (Candida albicans) . The in vitro activity of terbinafine is pH dependent and rises with increasing pH value.

Br Heart J, 1987 Sep, 58(3), 287 - 90
Infection of modified Blalock shunts; Carvalho JS et al.; A left-sided interposition graft (modified Blalock-Taussig anastomosis) was constructed with polytetrafluoroethylene in a three month old child with tetralogy of Fallot . This shunt thrombosed and a replacement shunt became the site of chronic Pseudomonas infection . The second anastomosis was excised and a third interposition graft was inserted on the right side because the anatomy was unsuitable for a classical Blalock-Taussig shunt . The patient died when he was 12 months old, after signs of infection and shunt occlusion had developed . At necropsy the acutely thrombosed right sided shunt was found to be the site of Candida albicans infection . Gallium and labelled white cell scans, computed tomography, and ultrasound scans had all failed to identify the sites of infection, which were only confirmed at operation or necropsy.

Medicine (Baltimore), 1987 Sep, 66(5), 341 - 8
Fatal infections in systemic lupus erythematosus: the role of opportunistic organisms; Hellmann DB et al.; The causes of death were examined in patients with systemic lupus erythematosus (SLE) who were cared for at the University of California, San Francisco and who died after 1969 . Of the 44 deaths analyzed, 33 patients had autopsies . Infections were common and often determined to be the cause of death . Overall, infections were present in 55 percent (22/44), and judged to be a cause of death in 30 percent (13/44) of all deaths . The infections could be divided into 2 groups: those due to common bacterial organisms and those due to opportunistic infections . These two types of infections occurred with similar frequency . When compared to common bacterial infections, however, the opportunistic infections were more likely to be first diagnosed at autopsy (p = .001) . In only 3 of the 15 patients with an opportunistic infection was the diagnosis made antemortem . Failure to diagnose an opportunistic infection early occurred when the infection simulated active SLE, and when the possibility of an opportunistic infection was not aggressively investigated . The most common opportunistic infections were Candida albicans and Pneumocystis carinii . The most common site of opportunistic infection was the lung . Seventeen patients had 27 common bacterial infections, chiefly sepsis from Staphylococcus aureus and aerobic gram-negative organisms . Eight patients had both a common bacterial and an opportunistic infection . Stepwise linear regression analysis showed that death from infection correlated most strongly with prednisone and cytotoxic drug use in the 3 months before final admission . No measure of lupus activity was found to correlate with death from infection, except that hypocomplementemia correlated with death from bacterial infections.(ABSTRACT TRUNCATED AT 250 WORDS)

J Clin Oncol, 1987 Sep, 5(9), 1461 - 8
Microbiology of acute periodontal infection in myelosuppressed cancer patients; Peterson DE et al.; This study characterized the subgingival microbial flora associated with 27 acute exacerbations of preexistent periodontal disease in 24 patients with chemotherapy-induced myelosuppression . All but two acute periodontal infections developed at low granulocyte levels (less than 1,000/microL) . Suspected pathogens were detected in high concentrations in subgingival plaque specimens in 17 episodes of acute periodontal infection; a single pathogen was recovered in ten acute infections, and more than one pathogen was recovered in seven acute infections . Staphylococcus epidermidis, Candida albicans, S aureus, and Pseudomonas aeruginosa predominated, with combinations of these detected in some patients . Concomitant bacteremias developed in two of these patients . The subgingival microflora associated with ten acute periodontal infections was characterized by predominantly indigenous microorganisms, which in nine episodes were in abnormal proportions compared with microbial profiles in noncancer patients with similar degrees of periodontal disease . These data demonstrate that pathogens normally associated with infections in myelosuppressed cancer patients, as well as indigenous oral flora, are associated with acute periodontal infections during granulocytopenia . This finding is important, since this body site has not commonly been recognized as a source for acute infection in these patients.

Brain Behav Immun, 1987 Sep, 1(3), 267 - 75
Effect of differential housing and time on immune reactivity to sheep erythrocytes and Candida; Rabin BS et al.; Male C3H/HeJ mice were housed 5 or 1 per cage for varying periods of time . Approximately 10-14 days after the animals were placed under the differential housing conditions, the reactivity of lymphocytes to concanavalin A and to intraperitoneal injection of sheep erythrocytes became greater in animals housed 1 per cage in comparison with those housed five per cage . By 3 weeks the immune reactivity was similar regardless of the number of animals housed per cage . Similarly, resistance to infection with Candida albicans was greater in animals housed one per cage at approximately 10-14 days after the animals had been isolated . By 3 weeks a difference in resistance to C . albicans was not apparent between animals housed 5 or 1 per cage . Thus, housing conditions can transiently alter immunologic reactivity, including susceptibility to an infectious agent in male C3H/HeJ mice . However, female C3H/HeJ mice and male C57BL/6J mice did not show an effect of housing conditions on immune reactions.

Proc Soc Exp Biol Med, 1987 Sep, 185(4), 434 - 40
The effect of 1,25-dihydroxyvitamin D3 on hematopoiesis in long-term human bone marrow cultures; Fabian I et al.; The modulatory effect of 1,25-dihydroxyvitamin D3 (vit D) on the growth of myeloid progenitors and on the composition of the stromal layer in human bone marrow long-term cultures was studied . Vit D (2 X 10(-8) M) caused an enhancement in myeloid progenitor cell (CFU-C) growth in the nonadherent and adherent layers during the entire 5-week incubation period . The vitamin did not alter the differentiation pattern of CFU-C (monocyte-macrophage progenitors CFU-M, granulocytic progenitors CFU-G, or monocyte-granulocyte progenitors CFU-GM) . Vit D caused a marked increase in the percentage of lipid-containing cells in the adherent layer and an increase in the number of cells that specifically bound My4 monoclonal antibody (McAb), that reacted positively to fluoride-sensitive alpha-naphthyl acetate esterase, and that phagocytosed Candida albicans (CA) . Concentrated supernatants harvested from control cultures showed significant levels of myeloid colony stimulating factor (CSF) activity . The addition of vit D to cultures for 5 weeks did not alter CSF levels . These results suggest that vit D may play a role in hematopoiesis by acting directly on the progenitor cells or via the stromal cell production of stimulatory factor(s).

J Med Microbiol, 1987 Sep, 24(2), 151 - 5
Variations in affinity to Candida albicans in vitro among human buccal epithelial cells; Sandin RL et al.; Using an in-vitro adherence assay it was observed that the number of Candida albicans cells that attached to individual buccal mucosal cells varied greatly . Three mucosal-cell characteristics--state of aggregation, size and viability--that might influence yeast adhesion in vitro were studied . The number of attached yeast cells per mucosal cell varied from 0 to 32 . The majority of buccal cells (88%) had none or very few yeasts attached, whereas a minority of cells (12%) bound more than one half of all the attached yeasts . In donors whose buccal cells had large numbers of attached yeasts this percentage increased and the number of cells with no attached yeast cells fell . Cells of an intermediate size (36-70 micron) had a greater affinity for yeasts than did cells of other sizes . Buccal cell viability appeared not to be necessary for adhesion of yeasts . No significant differences were observed in the number of yeast cells attached to single buccal cells compared with attachment to buccal cells within sheets . It would appear, therefore, that there are distinct subpopulations of epithelial cells with high and low affinity for attachment by C . albicans in vitro . Mucosal cell size or viability might influence this affinity.

J Med Microbiol, 1987 Sep, 24(2), 145 - 50
Studies on cell adhesion and concanavalin A-induced agglutination of Candida albicans after mannan extraction; Sandin RL; Candida albicans cells were treated with alkali and acid to extract preferentially the cell wall alpha-mannan . Cells were recovered at three stages, as extraction proceeded from mild to more extensive: Alk-1, Alk-2 and Alk + Acid . Yeast adhesion to human epithelial cells was then examined with an in-vitro adherence assay . Yeasts from all three stages of extraction adhered in significantly lower numbers to buccal mucosal cells than did unextracted yeasts . Adhesion was as low for Alk-1 cells as for those submitted to more complete mannan extraction . When yeast cells from all three stages were treated with Concanavalin A (Con A), a lectin probe with strong affinity for yeast alpha-mannans, and then subjected to the adherence assay, there was no significant change in adhesion . When yeast agglutinability by Con A was examined in tests with treated and untreated yeast cells, abundant agglutination occurred only with the untreated cells . However, Alk-1 cells, though lacking in adhesive capacity towards mucosal cells, showed significant agglutination . The results suggest that candidal adhesion is mediated by an alkali-soluble, mannan-containing moiety(ies) which appears to be lost early in the extraction process . Blockage of this moiety by Con A inhibits the adhesion of unextracted cells . Extracted cells lack this moiety but still possess enough structural mannan for Con A recognition and agglutination.

J Bacteriol, 1987 Sep, 169(9), 4393 - 5
Different levels of DNA methylation in yeast and mycelial forms of Candida albicans; Russell PJ et al.; Isotope dilution gas chromatography-mass spectrometry analysis of genomic DNAs isolated from three Candida albicans isolates showed significant differences in the amounts of 5-methyldeoxycytidine (m5Cyt) in DNA from yeast-form and from mycelial-form cells; the moles percent m5Cyt were 0.11, 0.11, and 0.097 for yeast-form DNA and 0.045, 0.053, and 0.047 for mycelial-form DNA for the three isolates Sh8, 9938, and B311, respectively . The lower m5Cyt values for mycelial-form cells suggest that those cells may exhibit significantly greater gene activity than yeast-form cells.

Infect Immun, 1987 Sep, 55(9), 2324 - 6
Purification of actin from Candida albicans and comparison with the Candida 48,000-Mr protein; Fiss E et al.; Actin was purified from Candida albicans cells by affinity chromatography by DNase-Sepharose and was recognized by immunoblotting with monoclonal antibody directed against chick muscle actin . The C . albicans 48-kilodalton protein recognized by sera from patients with invasive candidiasis was shown by DEAE chromatography and immunoblotting not to be identical with the purified C . albicans actin.

J Clin Immunol, 1987 Sep, 7(5), 400 - 9
Mannan-specific and mannan-induced T-cell suppressive activity in patients with chronic mucocutaneous candidiasis; Durandy A et al.; We have studied T- and B-cell responses to antigens of Candida albicans in 18 patients suffering from chronic mucocutaneous candidiasis . We have shown that in vitro production of antibody to one of these antigens, mannan, was absent during the active phase of the disease and that this absence was consequent to the activation of specific CD8(+) and CD8(-) suppressor T lymphocytes . Such activation was also observed when control T lymphocytes were incubated in the presence of monocytes and a high concentration of mannan . This suppressive effect was specific to antigens of Candida albicans, was radiosensitive, and was not consequent to the secretion of prostaglandin E2 . It appeared as well that the induction of these suppressor T cells was HLA-DQ restricted . The suppressor T-cell activity induced by antigens of Candida albicans in vitro is thus comparable to the suppressor T-cell activity observed in vivo in patients affected with chronic mucocutaneous candidiasis . Defective handling of mannan by monocytes could result in the accumulation of mannan, resulting in the activation of specific T suppressor cells and in the consequent cellular immunodeficiency specific to Candida albicans . Successful treatment of the candidiasis resulted in complete correction of the immune abnormalities.

J Clin Microbiol, 1987 Sep, 25(9), 1611 - 22
High-frequency switching in Candida strains isolated from vaginitis patients; Soll DR et al.; High-frequency switching and strain variability at the site of infection was assessed in 11 patients with acute Candida albicans vaginitis . By cloning cells directly from the site of infection, it was demonstrated that 4 of the 11 isolates contained multiple-switch phenotypes at the site of infection and that 9 of the 11 isolates were in a high-frequency mode of switching (10(-2) to 10(-3)) . Isolates could be separated into four general categories of switching repertoires . To demonstrate that multiple phenotypes at the site of a single infection represented the same strain, EcoRI digests of total cell DNA were separated on agarose gels, and Southern hybridization patterns with two cloned midrepeat sequences were compared.

Am J Surg Pathol, 1987 Sep, 11(9), 726 - 31
Demonstration of Epstein-Barr virus in immunoblastic sarcoma of B-cells arising in a child with primary immunodeficiency disease; Gartner JG et al.; The subject of this investigation was an 11-month-old infant girl who presented with a pathological fracture of the right femur due to a metastasis from an abdominal immunoblastic sarcoma . Her past history included recurrent, intractable bacterial and fungal infections . Investigations of her immune status revealed low numbers of T-lymphocytes, a reversed T-helper (TH)/T-suppressor (TS) cell ratio, no response of her peripheral blood lymphocytes to pokeweed mitogen, phytohemagglutinin, concanavalin A, and Candida albicans, and an inability of her cells to react in a mixed lymphocyte culture . Serum levels of IgG, IgM, and IgA were all below normal . No thymic shadow was visible on the chest radiograph . There was no evidence of adenosine deaminase or nucleoside phosphorylase deficiencies . The tumor cells exhibited both surface IgM and IgG, and many of the cells contained large amounts of cytoplasmic IgM . Light chain specificity was restricted to lambda chain for both surface and cytoplasmic immunoglobulin . Ultrastructural study of the tumor cells revealed the presence of both intranuclear and cytoplasmic virions in roughly 1% of the tumor cells . These viral particles strongly resembled herpes viruses . DNA-hybridization studies on the neoplasm revealed the presence of 7-10 genome equivalents of Epstein-Barr virus-DNA per tumor cell.

Am J Reprod Immunol Microbiol, 1987 Sep, 15(1), 34 - 7
Immunology of recurrent vaginitis; Witkin SS; Recent evidence suggests that recurrent vaginitis can arise as a consequence of a transient and localized inhibition of cell-mediated immunity . Lymphocytes from many women with this disorder manifest a reduced in vitro proliferative response to Candida albicans . The inhibition appears to be due to increased production by the patients' macrophages of prostaglandin E2, which inhibits interleukin-2 production and thereby blocks lymphocyte proliferation . When lymphocyte responses are impaired, C . albicans can readily proliferate and initiate a clinical infection . Prostaglandin E2 production can arise as a consequence of a vaginal allergic response . IgE antibodies to C . albicans, ryegrass, contraceptive spermicides, and seminal plasma have been detected in vaginal fluids from recurrent vaginitis patients . The role of male factors in inducing immune alterations and vaginitis in the female partner has been underestimated . Medications or chemicals ingested by the male and present in his semen may be transmitted to sensitized females by coitus . In addition, male-specific allergic responses may be induced in females through the seminal transfer of specific IgE antibodies . Future efforts both to eliminate clinical vaginal infections and to reduce susceptibility of the host to vaginal immunosuppression should improve the efficacy of treatment for this disorder.

J Ethnopharmacol, 1987 Aug, 20(3), 223 - 37
Screening of antimicrobial activity of plants popularly used in Guatemala for the treatment of dermatomucosal diseases; Caceres A et al.; Ethnobotanical surveys were conducted among traditional healers and local market vendors; about 200 plants used in Guatemala for the treatment of dermatomucosal diseases were detected . By literature review and according to local availability, 89 plants were selected for in vitro screening for antimicrobial activity against the microorganisms usually causing skin and mucosal infections . Ethanolic macerations were prepared and impregnated in absorbent paper; once dried, these were applied over standardized inocula of Candida albicans, Escherichia, coli, Pseudomonas aeruginosa and Staphylococcus aureus . After incubation, inhibition zones were measured, demonstrating that 28 of the plants exhibited some in vitro inhibition of the tested microorganisms.

J Antibiot (Tokyo), 1987 Aug, 40(8), 1146 - 64
Papulacandins--synthesis and biological activity of papulacandin B derivatives; Traxler P et al.; A series of papulacandin B derivatives was synthesized and their in vitro and in vivo activity against Candida albicans and other fungi was established . The biological data have shown that some 10-alkyl ether and 11-acylamino derivatives exhibit an improved in vivo activity compared to papulacandin B whereas derivatization in other positions of the molecule led to less potent compounds.

Klin Monatsbl Augenheilkd, 1987 Aug, 191(2), 125 - 8
{Experimental studies of local therapy of Candida keratomycosis with amphotericin B}; Behrens-Baumann W et al.; The efficiency of Amphotericin B drops was studied using a newly developed keratomycosis model (defined strain Candida albicans DSM 70010, which leads reproducibly to a corneal infection with descemetocele without prior local or systemic immunosuppression in the rabbit) . Penetration of the drug (administered ten times a day) into the cornea and aqueous humor was only demonstrated after abrasion of the corneal epithelium . Three groups were studied: (I) therapy with abrasion, (II) therapy without abrasion, and (III) a control group . Both clinically (descemetocele or perforation, hypopyon) and with regard to microbiology (reculture of Candida) the results obtained in Group I were significantly better than those obtained in Group II (p less than 0.001) . Repeated corneal abrasion is therefore recommended for treatment of Candida keratitis with Amphotericin B.

Chemioterapia, 1987 Aug, 6(4), 272 - 6
New benzofuran-imidazoles as antimycotic agents . II . In vitro studies; Riviera L et al.; Ten new imidazole derivatives, benzofuran-imidazoles, were studied in vitro to establish their antimycotic activity against 70 fungal strains, in comparison with three known imidazoles and, for the dermatophytes only, griseofulvin . A very high inhibitory activity against dermatophytes was shown by five of the new substances . The other filamentous fungi and yeasts showed a more marked variation in their susceptibility . However a good sensitivity of some isolates of Candida albicans and other yeasts was seen.

Epidemiol Infect, 1987 Aug, 99(1), 213 - 9
An epidemiologic study of the fungal skin flora among the elderly in Alexandria; Gad ZM et al.; The fungal skin flora of a sample of 205 elderly persons in Alexandria, drawn by cluster sampling probability technique, was investigated . Pathogenic yeasts were isolated from 18.6% and 10.3% of skin and nails respectively . Candida albicans (16.1% and 7.3%) was prominent . A low prevalence of dermatophytes grown on agar (2.4% from skin and 2.9% from nails) was observed . In contrast, saprophytic filamentous fungi comprised 45.4 and 50.7% of skin and nails samples respectively . This study showed no statistically significant effect of sociodemographic variables (sex, marital status, crowding index, and income per capita) on the skin flora . There was no statistical significant difference between elderly diabetics and non-diabetics as regards fungal skin flora.

Epidemiol Infect, 1987 Aug, 99(1), 201 - 11
Four outbreaks of nosocomial systemic candidiasis; Burnie JP et al.; Candida albicans has recently been described as a cause of nosocomial infection . This paper reports four further outbreaks occurring over a 12-month period in England . There were 13 systemic cases and 6 deaths . The outbreaks were defined by morphotyping and the new technique of immunoblot fingerprinting . Control of the outbreaks was produced by the implementation of strict cross-infection control policies without recourse to systemic chemoprophylaxis.

Am J Gastroenterol, 1987 Aug, 82(8), 766 - 8
Esophageal ulcers caused by Torulopsis glabrata in a patient with acquired immune deficiency syndrome; Tom W et al.; Esophagitis due to an opportunistic infection in an immunocompromised host is not unusual . This is frequently attributed to Candida albicans . Torulopsis glabrata is similar however taxonomically distinct from C . albicans . Although found to be pathogenic in various organs, to date there have been only four reported cases of T . glabrata esophagitis . None of these was associated with acquired immune deficiency syndrome . The present paper discusses a patient with acquired immune deficiency syndrome found to have T . glabrata esophagitis with ulcerations.

J Lab Clin Med, 1987 Aug, 110(2), 237 - 44
Effect of 1,25-dihydroxyvitamin D3 and 13-cis-retinoic acid on in vitro hematopoiesis in the myelodysplastic syndromes; Nagler A et al.; The effect of 2 X 10(-10) to 2 X 10(-7) mol/L 1,25-dihydroxyvitamin D3 (1,25{OH}2D3) and 10(-9) to 10(-6) mol/L 13-cis-retinoic acid on in vitro differentiation and proliferation of marrow cells from patients with myelodysplastic syndrome (MDS) was assessed . Cells from 17 patients were studied by the semisolid technique, and cells from seven patients by both liquid and semisolid cultures . After incubation in liquid culture with 1,25(OH)2D3, in six of seven patients evaluated an increasing number of myeloid cells (185% to 470%) acquired the morphologic appearance of mature monocyte-macrophages, and a decrease in the number of immature myeloid cells (26% to 75%) was observed . Phagocytosis and killing of Candida albicans by monocyte-macrophages incubated with 1,25(OH)2D3 were normal and similar to those processes in untreated cells . 1,25(OH)2D3 increased the percentage of monocytes that phagocytosed C . albicans in three patients . Thirteen of 17 patients showed reduced myeloid cloning, and eight showed increased cluster formation . Cloning efficiency was significantly lower in patients with refractory anemia with excess of blasts and chronic myelomonocytic leukemia . Concentrations of 2 X 10(-9) to 2 X 10(-8) mol/L 1,25(OH)2D3 and 10(-8) to 10(-7) mol/L retinoic acid had a stimulatory effect on myeloid colony growth in five of the six patients with sideroblastic and refractory anemia, but in only two of the 11 patients with refractory anemia with excess of blasts and chronic myelomonocytic leukemia . The results indicate that the differentiation pattern of myeloid precursor cells from a subset of patients with MDS was altered by exposure to 1,25(OH)2D3.

Postgrad Med J, 1987 Aug, 63(742), 695 - 8
Candida albicans vertebral osteomyelitis in chronic renal failure; Neale TJ et al.; Invasive candidal infections are encountered with increasing frequency in compromised hosts but bone infection is uncommon . A woman with systemic lupus erythematosus and end-stage renal failure managed by continuous ambulatory peritoneal dialysis developed a painful thoracic kyphosis and a lytic lesion in the vertebral bodies of T10 and T11 . Blood cultures were sterile but bone biopsy material contained Candida albicans which also grew on culture . Circulating immune complexes were measured in high levels and contained candida antigens and specific anti-candida antibody as determined by isoelectric focusing, immunoblotting and immunoprinting techniques . Pain persisted after anti-fungal therapy had sterilized the lesion necessitating surgical excision of affected vertebrae, kyphosis correction and iliac crest bone grafting . The titres of circulating immune complexes and anti-candidal precipitins closely paralleled the clinical course.

J Gen Microbiol, 1987 Aug, 133 ( Pt 8), 2315 - 25
Formation of a new cell wall by protoplasts of Candida albicans: effect of papulacandin B, tunicamycin and Nikkomycin; Elorza MV et al.; Incorporation of polysaccharides into the walls of regenerating protoplasts of Candida albicans was followed in the presence of papulacandin B, tunicamycin and nikkomycin . With the first drug, chitin was incorporated normally whereas incorporation of glucans and mannoproteins was significantly decreased . Tunicamycin decreased incorporation of all wall polymers when added at the beginning of the regeneration process but blocked only mannan and alkali-insoluble glucan incorporation when added after 5 h . Nikkomycin inhibited chitin synthesis, and the walls formed by the protoplasts were enriched in alkali-soluble glucan . Pulse-chase experiments suggested that a precursor-product relationship between the alkali-soluble and alkali-insoluble glucans existed in the wall . The results obtained with the antibiotics were confirmed and extended by cytological studies using wheat-germ agglutinin labelled with colloidal gold and concanavalin A-ferritin as specific markers of chitin and mannoproteins respectively . The results support the idea that regeneration of walls by protoplasts occurs in two steps: firstly, a chitin microfibrillar skeleton is formed, and in a later step glucan-mannoprotein complexes are added to the growing structure . The chitin skeleton probably allows the orderly spatial arrangement of the other polymers giving rise to the regenerated cell wall.

J Gen Microbiol, 1987 Aug, 133 ( Pt 8), 2181 - 90
Production of long-chain alcohols by yeasts; White MJ et al.; Fourteen yeast strains from six genera were analysed for the presence of long-chain alcohols . Six strains from three genera contained long-chain alcohols, highest levels being found in Candida albicans . The alcohols were identified and determined by TLC, GLC and GLC-MS . The major long-chain alcohols synthesized by these organisms were saturated, primary alcohols with C14, C16 or C18 chain length . Unsaturated long-chain alcohols were not detected . In all strains that produced long-chain alcohols, the relative proportions were C16 greater than C18 greater than C14 . Long-chain alcohol contents were higher in organisms from anaerobically, as compared with aerobically, grown cultures reaching about 650 micrograms (g dry wt organisms)-1 in stationary-phase cultures of C . albicans . In cultures of C . albicans, synthesis of long-chain alcohols occurred only after the end of exponential growth . The alcohols were predominantly present as free alcohols . The fatty-acyl chain-length profile of the triacylglycerol and to a lesser extent the sterol/wax ester fractions from C . albicans reflected that of the long-chain alcohols produced by this yeast.

J Gen Microbiol, 1987 Aug, 133 ( Pt 8), 2097 - 106
A mutant of Candida albicans deficient in beta-N-acetylglucosaminidase (chitobiase); Jenkinson HF et al.; A mutant of Candida albicans ATCC 10261 was isolated that was defective in the production of beta-N-acetylglucosaminidase (chitobiase) . The mutant grew normally in minimal medium supplemented with either glucose or N-acetyl-D-glucosamine (GlcNAc) as carbon and energy source, and the cells formed germ-tubes at 37 degrees C when induced to do so with GlcNAc . However, unlike the wild-type parent strain, the mutant strain did not utilize N,N'-diacetylchitobiose for growth . The mutant and parent strains had similar growth rates on glucose or GlcNAc, similar rates of uptake of these sugars and similar rates of 14C-labelled amino acid incorporation . The chitobiase mutant did, however, contain 53-85% more chitin than the wild-type strain . No reversion of the mutant phenotype was observed following induction of mitotic recombination with UV light, suggesting that the mutant allele (chi) was carried homozygously in the chitobiase-deficient mutant . Although the chitobiase-deficient mutant was pathogenic, it was not as virulent as the wild-type strain.

Mol Gen Genet, 1987 Aug, 209(1), 170 - 4
An electrophoretic karyotype for Candida albicans reveals large chromosomes in multiples; Lott TJ et al.; Using field-inversion gel electrophoresis we defined an electrophoretic karyotype for the yeast, Candida albicans . The karyotype is distinct from other species of Candida and is species specific . A total of five distinct chromosomal mobility groups were observed, at least four of which are composed of a minimum of two fragments each . From the apparent sizes of these fragments relative to the large chromosomes of the morphologically related yeast Saccharomyces cerevisiae, together with the known genome size of this organism, we conclude that the karyotype is the result of the migration of intact chromosomes.

J Clin Lab Immunol, 1987 Aug, 23(4), 203 - 8
Enhancement of host defence by Y-19995 (2,4'-bis(1-methyl-2-dimethyl-aminoethoxyl)-3-benzoylpyridine dimaleate), a novel synthetic compound . I . Accelerated restoration from the leukocytopenia and augmented protection against microbial infections in immunocompromised mice; Fujisawa H et al.; Effects of a novel synthetic compound, Y-19995, on the host defence in immunocompromised mice were investigated in terms of the restoration of leukocytopenia and the protection against several microbial infections . Oral or intravenous administration of Y-19995 into mice after X-irradiation, treatment with cyclophosphamide or mitomycin C prevented the leukocytopenia to some extent and promoted the restoration in cell numbers of both the peripheral blood leukocytes and bone marrow . Intravenous administration of Y-19995 increased significantly the survival rates of X-ray irradiated mice against acute systemic infections with Escherichia coli, Pseudomonas aeruginosa and Candida albicans, and intramuscular infection with Escherichia coli . The clearance of Escherichia coli from the blood of X-ray irradiated mice was also promoted by the treatment with Y-19995 . The augmented protection against microbial infections in immunocompromised hosts by Y-19995 may be attributed mainly to the prevention of leukocytopenia or the enhanced restoration from leukocytopenia.

J Med Vet Mycol, 1987 Aug, 25(4), 269 - 77
Induction of petite mutation with acriflavine and elevated temperature in Candida albicans; Aoki S et al.; A method of inducing respiratory deficient (petite) mutation in Candida albicans (which has been previously classed as a petite-negative yeast) and characteristics of some isolated mutants are reported . When grown at 42 degrees C in the presence of a cytoplasmic mutagen (acriflavine), C . albicans exhibited diauxie-like biphasic growth . Mutants which were unable to grow on a non-fermentable substrate, glycerol, were isolated from the above culture at a frequency of less than 1% . The simultaneous action of both acriflavine and a supraoptimal temperature of 42 degrees C was required to induce respiratory mutation . The respiratory mutants were separated into two groups: i . mutants exhibiting a complete cytochrome spectrum but with low respiratory activity and ii . those deficient in cytochrome aa3 . Further characterization of their respiratory activity, colony morphology, mitochondrial morphology and growth manner supported the evidence that members of the latter group can be regarded as petite mutants.

J Parasitol, 1987 Aug, 73(4), 769 - 73
Macrophage function in patients with American cutaneous leishmaniasis: in vitro cytotoxicity and interleukin-1 production; Ridel PR et al.; Monocyte-derived blood macrophages of untreated patients with Leishmania braziliensis or Leishmania mexicana amazonensis infections show anomalies in their nonspecific immune functions . Their ability to kill HeLa cells or to produce interleukin-1 in vitro in response to lipopolysaccharide plus Candida albicans is lower than controls indicating that acquired or innate macrophage deficiencies may be involved in the course of the disease.

Am Rev Respir Dis, 1987 Aug, 136(2), 266 - 70
Comparative oxidative microbicidal activity of human blood monocytes and alveolar macrophages and activation by recombinant gamma interferon; Kemmerich B et al.; The relative oxidative and microbicidal activities of human blood monocytes compared with those of alveolar macrophages (AM) are poorly defined . Furthermore, the comparative efficiency of recombinant gamma interferon (rIFN gamma) to enhance microbicidal function of these 2 cell populations is uncertain . In this study, blood monocytes and AM were obtained concomitantly from 10 healthy, nonsmoking human subjects . Cells were adjusted to equivalent cell concentrations and assayed for respiratory burst activity (superoxide anion production) during soluble (Concanavalin A) or particulate (bacteria) stimulation . Microbicidal activity against Pseudomonas aeruginosa, Listeria monocytogenes, and Candida albicans was also determined for each cell type . Finally, the capacity of rIFN gamma treatment (200 U/ml for 24 h) to enhance these cellular activities was determined . Oxidative activity of AM was greater than that of blood monocytes (p less than 0.01, bacteria; p less than 0.02, Con A) . Likewise, AM exhibited greater killing of P . aeruginosa (p less than 0.01) and L . monocytogenes (p less than 0.01) than did monocytes . Neither cell killed C . albicans . Treatment with rIFN gamma greatly enhanced both respiratory burst and microbicidal activity of blood monocytes, but had no effect on AM respiratory burst . Despite this, rIFN gamma-treated AM did exhibit some enhanced killing of L . monocytogenes (p less than 0.05) . We conclude that oxidative microbicidal activity of resident AM greatly exceeds that of blood monocytes, but that blood monocytes are relatively more susceptible to activation by rIFN gamma.

J Med Chem, 1987 Aug, 30(8), 1463 - 9
Methotrexate analogues . 30 . Dihydrofolate reductase inhibition and in vitro tumor cell growth inhibition by N epsilon-(haloacetyl)-L-lysine and N delta-(haloacetyl)-L-ornithine analogues and an acivicin analogue of methotrexate; Rosowsky A et al.; Analogues of methotrexate (MTX) with strong alkylating activity were prepared by replacing the L-glutamate side chain with N omega-haloacetyl derivatives of L-lysine and L-ornithine . Haloacetylation was accomplished in 30-40% yield by reaction of the preformed L-lysine and L-ornithine analogues of MTX with p-nitrophenyl bromoacetate or chloroacetate in aqueous sodium bicarbonate at room temperature . All four haloacetamides were potent inhibitors in spectrophotometric assays measuring noncovalent binding to purified dihydrofolate reductase (DHFR) from L1210 cells . In experiments designed to measure time-dependent inactivation of DHFR from L1210 cells and Candida albicans, the N epsilon-(bromoacetyl)-L-lysine and N delta-(bromoacetyl)-L-ornithine analogues gave results consistent with covalent binding, whereas N epsilon- and N delta-chloroacetyl analogues did not . The N delta-(bromoacetyl)-L-ornithine analogue appeared to be the more reactive one toward both enzymes . Amino acid analysis of acid hydrolysates of the L1210 enzyme following incubation with the bromoacetamides failed to demonstrate the presence of a carboxymethylated residue, suggesting that alkylation had perhaps formed an acid-labile bond . In growth inhibition assays with L1210 cultured murine leukemia cells, the four haloacetamides were all more potent than their nonacylated precursors but less potent than MTX . The greater than 40,000-fold MTX-resistant mutant cell line L1210/R81 was only partly cross-resistant to the haloacetamides . An analogue of MTX with acivicin replacing glutamate was a potent inhibitor of DHFR from chicken liver and L1210 cells but was 200 times less potent than MTX against L1210 cells in culture.

Chest, 1987 Aug, 92(2), 237 - 40
Significance of the tuberculin test in the elderly; Dorken E et al.; Nine hundred thirty-three persons over 65 years of age, residing in long-term or extended-care facilities in Vancouver, Canada, had tuberculin tests . In addition to PPD-tuberculin, 5 TU and 250 TU, we used PPD-Battey, Candida albicans, mumps, and Trichophyton antigens . Twenty-five percent reacted to 5 TU of tuberculin with reactions of 10 mm or more . There was a progressive, substantial loss of reactivity with advancing age . Reactions to PPD-Battey greater than to PPD-T 5 TU were infrequent, suggesting that atypical mycobacterial infections were uncommon and that positive reactions to PPD-T, 250 TU, were predominantly caused by infections with Mycobacterium tuberculosis . Based on the results of both 5 TU and 250 TU, the prevalence of tuberculous infection exceeded 60 percent . Waning of tuberculin sensitivity appears to be an integral part of the aging process . Testing with nonmycobacterial antigens used in this study shed no further light on the problem of anergy in the elderly, as the number of reactors was smaller than that obtained with PPD-tuberculin.

J Immunol Methods, 1987 Jul 16, 101(1), 37 - 42
A rapid fluorescent assay to distinguish attached from phagocytized yeast particles; Levitz SM et al.; In studies of phagocytosis and its consequences for cell activation, it is important to distinguish those particulate stimuli which are completely ingested and internalized from those which are only attached to phagocytic surfaces . Ingestion can be profoundly influenced by both the type of opsonins on the surface of the stimulus and the expression and activation of receptors on the phagocytes for these opsonins . We report a new fluorescent assay which facilitates rapid and reproducible quantitation of attached versus fully internalized live or dead yeast particles by phagocytes . The assay employs the fluorescent dye diaethanol (Uvitex 2B) which stains chitin on the cell wall of fungi and is excluded from live phagocytes . The diaethanol assay and a standard, previously published methylene blue dye exclusion assay yielded comparable results using human neutrophils or monocytes incubated with heat-killed, serum-opsonized Candida albicans . The diaethanol assay proved useful in distinguishing differences in effects of various opsonins, as human neutrophils selectively opsonized with either pooled human serum (PHS), IgG (heat-inactivated PHS) or complement (IgG-depleted PHS) completely internalized 69.5%, 91.3% and 52.5% of cell-associated zymosan particles respectively . Finally, the new assay permitted comparisons of differing macrophage populations, as resident murine peritoneal macrophages internalized only 10.6% of complement-opsonized, cell-associated zymosan particles compared with 41.7% when the macrophages were elicited with thioglycolate . The assay should prove useful to investigators studying both fungal phagocytosis and killing, as well as to those performing general studies of receptor expression, regulation and function.

Am J Ophthalmol, 1987 Jul 15, 104(1), 57 - 60
Candida albicans endophthalmitis after penetrating keratoplasty; Insler MS et al.; We examined two patients who received contaminated corneas from the same organ donor during penetrating keratoplasty . Both developed Candida albicans endophthalmitis, which responded to surgical and antifungal therapy . On follow-up examination one patient had a visual acuity of hand motions, a pupillary membrane, and a macular scar . The other had a visual acuity of 20/100 and a clear graft.

J Immunol, 1987 Jul 15, 139(2), 417 - 21
Enhanced killing of Candida albicans by murine macrophages treated with macrophage colony-stimulating factor: evidence for augmented expression of mannose receptors; Karbassi A et al.; The effect of macrophage colony-stimulating factor (CSF-1) on killing of Candida albicans by murine peritoneal macrophages was determined . The killing capacity of resident peritoneal macrophages was unaffected by CSF-1 . However, proteose-peptone-elicited peritoneal exudate macrophages that had been pretreated with CSF-1 (greater than or equal to 1000 U/ml) for 24 or 48 hr exhibited a significantly enhanced capacity to kill C . albicans . CSF-enhanced killing appeared to be independent of endogenously produced interferon-alpha/beta (IFN) in that enhancement by these two agents differed with regard to onset of the effect, target cell responsiveness, and duration of augmented killing . In addition, a highly specific anti-IFN antiserum that totally neutralized IFN augmentation of candidacidal activity had no effect on CSF-induced enhancement . Evidence was obtained indicating that CSF, unlike IFN, augmented mannose-inhibitable binding and ingestion of C . albicans, suggesting that augmented expression of mannose-receptors by CSF-treated macrophages was at least partially responsible for the enhanced killing.

Ann Allergy, 1987 Jul, 59(1), 48 - 51
Chronic asthma and rhinitis due to Candida albicans, epidermophyton, and trichophyton; Gumowski P et al.; Asthma and rhinitis due to Candida albicans is well known . Trichophyton and Epidermophyton are not usually considered as causal agents for these diseases . During the years 1982 and 1983 all of the cases of chronic asthma or rhinitis exhibiting a positive immediate skin response (greater than or equal to 10 mm) to one of these three antigens were selected for this study (60 asthma and 75 rhinitis) . They all went through nasal and bronchial provocation tests with the specific antigen . Late reactions were also registered . A RAST was performed in some of the patients reacting to Candida albicans . Following inhalation challenge with antigens, an immediate response was obtained in 91 cases (asthma 30, rhinitis 51) . A dual response was observed in 17 cases of asthma and in 13 cases of rhinitis . A RAST-Candida albicans was done in 64 cases . Results were positive in 52 patients . In 46 cases there was a correlation between the RAST and the provocation tests . Hyposensitization treatment was given to 92 patients . After 2 years of treatment, a good to excellent response could be observed in almost 60% of the treated cases . A rough estimation of the incidence of immediate bronchial and nasal hypersensitivity among patients with chronic asthma and rhinitis to the three yeasts gives the approximate figure of 8% to 10%.

Infect Immun, 1987 Jul, 55(7), 1558 - 63
Factors affecting colonization and dissemination of Candida albicans from the gastrointestinal tract of mice; Ekenna O et al.; Male ICR Swiss mice (2 to 3 months old) were fed Candida albicans in their drinking water for 3 days, followed by no treatment, antibiotics in their drinking water (daily), or immunosuppressants given by intraperitoneal injection (two to three times weekly) over a 3- to 4-week period . The organs of animals were processed to determine the numbers of C . albicans and total aerobic bacteria per g of tissue . Untreated animals had mean Candida counts during the 1-month period of 10(2.3) CFU/g of cecum . Animals in six of eight antibiotic-treated groups had mean cecal Candida counts higher than those of control animals (P less than 0.05), with clindamycin-gentamicin producing the highest counts (10(4.7) CFU/g) . Cyclophosphamide produced counts (10(4.3) CFU/g) which were higher (P less than 0.05) than those resulting from methotrexate (10(3.0) CFU/g) or steroid (10(2.7) CFU/g) treatment . Cyclophosphamide-clindamycin-gentamicin treatment was associated with the highest (P less than 0.05) levels of Candida colonization (10(6.5) CFU/g) . Mice receiving immunosuppressants plus clindamycin-gentamicin were more likely to disseminate C . albicans than were mice receiving antibiotics alone (P less than 0.001) . Our findings suggest that colonization of the guts of mice by C . albicans can be facilitated by manipulating the aerobic, anaerobic, or both types of gut flora . The combined effect of immunosuppressants on both Candida gut colonization and dissemination appears multifactorial and deserves further investigation.

Rev Infect Dis, 1987 Jul-Aug, 9 Suppl 4, S400 - 3
Role of fibronectin in the pathogenesis of candidal infections; Calderone RA et al.; Adherence of Candida albicans yeast cells to mammalian cells in vitro is promoted by a cell-surface adhesin that is probably a mannan or a mannoprotein . This observation is based on results of studies that utilized either lectins or antibodies to Candida that block attachment . Selective enzymatic degradation of cell wall constituents has been used to define the surface ligand of the candidal cell . Recently, nonadhering, spontaneous mutants of C . albicans, from both yeast and mycelial forms, that lack specific mannoproteins have been described . In addition, such mutants are avirulent, an indication that attachment plays a role in the disease process . The mammalian receptor for Candida has not been identified, but in endocarditis it could be fibronectin, both because fibronectin is present at the endocardial lesion and because those Candida species that bind to fibronectin in vitro exhibit a high disease potential; i.e., Candida species that bind to fibronectin in vitro also cause endocarditis, while those that do not bind in vitro do not cause disease . Attachment of yeast cells both to human buccal and vaginal epithelial cells is reduced significantly if yeast cells are preincubated with fibronectin, a finding that indicates a possible role for fibronectin as the epithelial surface receptor for Candida.

J Pediatr Gastroenterol Nutr, 1987 Jul-Aug, 6(4), 575 - 80
Effect of intralipid on the phagocytic and microbicidal capacity of human monocytes in culture; Padeh S et al.; We studied the effect of Intralipid (IL) in monocyte cultures based on the ability of the cultures to phagocytose and kill Candida albicans and produce the oxidative burst . The IL was taken up by monocytes in cultures, and these cells phagocytosed more Candida organisms than did the control cells {85 +/- 2.2% in the IL treated (1%) compared to 68 +/- 2.3% after 1 h in the control} . The percentage of killing of Candida albicans, which had been taken up by the IL-treated monocytes measured after 2 h in culture (48.3 +/- 6.0%), was no different when compared to control (47.0 +/- 5.8%) . Following ingestion of IL, there was an increase in basal H2O2 production, however, the presence of the IL in the cells had no effect on the expected increase in H2O2 production following stimulation with either phorbol myristate acetate (PMA) or zymosan particles . Compared to untreated cells, a significant increase in the number of monocytes with positive nitroblue tetrazolium staining was observed in monocytes that had ingested IL (when they were stimulated with either PMA or Candida microorganisms) . Similar results were obtained in monocyte-derived macrophages (i.e., monocytes in monolayer cultures for 10 days) . These findings suggest that the essential monocyte functions of phagocytosis, microbicidal activity, and ability to elicit an oxidative burst are not directly altered by the conventional use of IL in clinical practice.

Infection, 1987 Jul-Aug, 15(4), 308 - 10
Serologic response to Candida albicans and Aspergillus fumigatus in cystic fibrosis; Przyklenk B et al.; In order to evaluate the role of fungi in patients with cystic fibrosis, we determined serum IgG antibodies against Candida albicans and Aspergillus fumigatus using an indirect ELISA in patients with or without fungi in the sputum and in sera of healthy individuals . For both C . albicans and A . fumigatus the antibody levels were significantly higher in the CF groups than in the control group, regardless of whether these fungi could be isolated during the observation time or not . In contrast to A . fumigatus, we found that in the majority of cases antibody levels increase significantly with the isolation of C . albicans from sputum . Therefore, we conclude that one has to pay more attention to C . albicans in CF patients . One must also particularly reevaluate long-term antibiotic treatment and look for means to prevent fungal recolonization and reinfection.

Mycopathologia, 1987 Jul, 99(1), 31 - 9
Selective inactivation of heterokaryons of Candida albicans by anaerobiosis; Sarachek A; Heterokaryons (hets), but not monokaryons of Candida albicans die when grown anaerobically on minimal medium . Their rates of inactivation increase with decreases in growth temperatures from 37 degrees C to 25 degrees C . At 10 degrees C, however, anaerobiosis is not lethal and suppresses the inactivation which normally occurs among hets cultured aerobically at that temperature . Killing of hets by anaerobiosis can be altered significantly by certain exogenously provided amino acids or intermediates of oxidative respiration . Aspartic acid alone promotes inactivation whereas alanine, glutamic acid or lysine individually have no effects . However, glutamate and lysine combined afford slight protection against inactivation while aspartate and glutamate combined, with or without lysine, are highly protective: the activity of the aspartate-glutamate combination is completely negated by the addition of alanine . Other common amino acids have no effects on het responses to anaerobiosis other than the ability, when combined, to relieve the antagonism of alanine for the aspartate-glutamate combination . Anaerobic survivals are also enhanced by oxalacetic acid or alpha-ketoglutaric acid, and even more so by a combination of these two intermediates . The resistances to inactivation elicited by the oxalacetate alpha-ketoglutarate or aspartate-glutamate combinations are not additive . These relationships are interpreted to signify that inactivation of hets by anaerobic growth is largely, if not exclusively, due to depletion of their oxalacetic acid and alpha-ketoglutaric acid contents for amino acid biosyntheses, and the unique inability of het cells to replenish those keto acids upon subsequent return to aerobic conditions . The observations are consistent with previous indications that mitochondria formed by hets are functionally abnormal.

Aviat Space Environ Med, 1987 Jul, 58(7), 673 - 8
Combined effects of hyperbaric oxygen and antifungal agents on the growth of Candida albicans; Gudewicz TM et al.; The effects of hyperbaric oxygen (HBO) and antifungal agents on Candida albicans were studied . Growth curves at O2 tensions of 160 mm Hg, 900 mm Hg, and 1800 mm Hg for prolonged exposures showed no effect of pressure alone . There was a significant dose response to increasing O2 tension; growth inhibition occurred at 900 mm Hg O2 and killing at 1800 mm Hg O2 . Minimum inhibitory concentrations (MIC) and minimum cidal concentrations (MCC) at 160 and 900 mm Hg O2 were done using amphotericin B, nystatin, clotrimazole, miconazole, ketoconazole and 5-fluorocytosine . MIC and MCC's were done with amphotericin B at 90-min exposures to 1800 mm Hg O2 . There was no enhancement of MIC or MCC at 900 mm Hg O2 . However, ketoconazole was ineffective at killing at 900 mm Hg O2 indicating a protective effect of HBO with this drug . Oxygen tensions of 1800 mm Hg for 90 min in the presence of amphotericin B showed an enhancement of both MIC and MCC . Closer quantitation of this effect upon the in vitro growth and survival of the organism showed an additive but not synergistic effect.

Infect Immun, 1987 Jul, 55(7), 1663 - 7
Discrepancy in assessment of phagosome-lysosome fusion with two lysosomal markers in murine macrophages infected with Candida albicans; Mor N et al.; Phagosome-lysosome fusion (P-LF) was studied in cultured mouse resident peritoneal macrophages after phagocytosis of Candida albicans . The macrophages were labeled with acridine orange (AO), the electronopaque colloidal Thorotrast, or both markers . After phagocytosis of heat-killed C . albicans, both markers were delivered to more than 95% of phagosomes . After ingestion of viable C . albicans by labeled cells, delivery of AO to phagosomes was highly suppressed (90%), and yet Thorotrast delivery was almost universal . After phagocytosis and 60 min of incubation, about 10 to 20% of the yeasts were killed, and a similar fraction of phagosomes was stained by the fluorescent marker . The evidence from Thorotrast transfer and assessment of yeast viability indicates that C . albicans largely resists intracellular killing by resident macrophages in the face of entirely uninhibited P-LF . We infer that AO must transfer to nearly all of the phagosomes but that it is evidently recognizable only in those in which the yeasts have been killed or possibly severely injured . This conclusion constitutes yet another limitation in the usefulness of AO for studying P-LF.

Postgrad Med J, 1987 Jul, 63(741), 563 - 5
Candidal endophthalmitis: a manifestation of systemic candidiasis; Patel BC et al.; Two patients on total parenteral nutrition who developed endophthalmitis secondary to Candida albicans are described . Candidal endophthalmitis as a manifestation of systemic candidiasis is discussed and its early diagnosis by bedside fundal examination in patients at risk is stressed.

JPEN J Parenter Enteral Nutr, 1987 Jul-Aug, 11(4), 394 - 7
The growth of microorganisms in total parenteral nutrition admixtures; D'Angio R et al.; Total nutrient admixtures (TNAs) containing glucose, amino acids, and lipid emulsion in one container and amino acid/dextrose solutions {conventional total parenteral nutrition (TPN) formulations} were studied in a controlled laboratory experiment for their ability to support the growth of microorganisms . Both TNA and conventional TPN formulations for peripheral and central venous administration with standard additives were inoculated with microorganisms to provide 10(1)-10(2) colony-forming units/ml (CFU/ml) of Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Candida albicans . The admixtures were stored at room temperature and samples for quantitative microbiology were taken at time 0, 6, 12, 24, 48, 72, and 96 hr . K . pneumoniae, E . coli, and P . aeruginosa were able to proliferate in central TNAs, but the growth of these organisms was retarded in conventional TPN solutions . In the peripheral formulations, K . pneumoniae and E . coli proliferated in both the TNA and conventional TPN systems, whereas P . aeruginosa grew well only in the peripheral TNA . S . epidermidis was not able to grow in any admixtures tested; however, C . albicans grew well in all admixtures, but growth was slower in the conventional central TPN . In conclusion, peripheral and central TNAs supported the growth of microorganisms significantly better than conventional TPN solutions.

Drug Intell Clin Pharm, 1987 Jul-Aug, 21(7-8), 633 - 8
Growth of microorganisms in total nutrient admixtures; Rowe CE et al.; It has been reported that intravenous fat emulsions, because of their isotonicity and neutral pH, support microbial growth, but traditional parenteral nutrition solutions, being hypertonic and more acidic, are not as supportive . To date, few studies have documented microbial growth in total nutrient admixtures (TNA) containing dextrose, amino acids, fat, electrolytes, vitamins, and trace elements . This study was undertaken to analyze the growth of Staphylococcus aureus, Candida albicans and four gram-negative enteric bacilli in three different nutrient admixtures, with and without the inclusion of 5% fat emulsion . The composition of the admixtures was either 5, 10, or 25% dextrose; either 0 or 5% fat; and 3% amino acids, electrolytes, vitamins, and trace elements . All admixtures were innoculated with 100 colony-forming units per milliliter, incubated at room (25 degrees C) or refrigerated (4 degrees C) temperature, with samples withdrawn at 0, 3, 6, 12, 24, and 48 hours and plated in triplicate . Only C . albicans demonstrated any significant growth regardless of fat content . The pH of the admixtures was similar (acidic), and all solutions were hypertonic and found to inhibit bacterial growth . Conclusions suggest that TNA, when formulated with normal concentrations of additives, is no more likely to support growth of contaminant organisms than the traditional solutions . This contradicts the notion that the addition of fat to total parenteral nutrition will enhance the ability of these admixtures to support microbial growth.

Hum Immunol, 1987 Jul, 19(3), 163 - 77
Differential antigen presentation by heat-treated peripheral blood mononuclear cells and Epstein-Barr virus-transformed lymphoblastoid cell lines (EBV-LCL): heated EBV-LCL present alloantigen and soluble antigen but are deficient in the stimulation of autologous EBV-LCL primed T cells; Mandell RB et al.; Heat-treated PBM (1 hr at 45 degrees C) cannot present soluble Candida albicans antigens (CAN) or stimulate in the mixed lymphocyte culture (MLC) reaction . This is despite their continued expression of serologically defined class II MHC antigens . In contrast, heat-treated EBV-LCL present soluble CAN and stimulate allogeneic T cells in the MLC . Heated EBV-LCL stimulate strong secondary responses from allogeneic alloprimed T-cell lines in the primed lymphocyte test (PLT), while heated PBM stimulate only weak secondary allogeneic responses . To test whether this difference was due to a subtle difference in the thermal stability of the functional expression of class II MHC antigens on PBM and EBV-LCL cells, the EBV-LCL cells were heated for 1 hr at temperatures from 45 degrees C to 60 degrees C . Even after treatment at 60 degrees C, the heated EBV-LCL strongly stimulated alloreactive T cells in MLC and PLT reactions . Heated EBV-LCL are not nonspecifically mitogenic, as they do not stimulate autologous T-cell lines primed to alloantigens . However, the weak response of alloprimed T-cell lines to heated allogeneic PBM can be augmented by coculturing with autologous heated EBV-LCL, suggesting heated EBV-LCL maintain a metabolic activity necessary for allogeneic stimulation that is deficient in heated PBM . While heated EBV-LCL stimulate allogeneic alloprimed T-cell lines, they no longer stimulate autologous EBV-LCL primed T-cell lines; irradiated EBV-LCL stimulate both strongly . This suggests the involvement of a heat labile antigenic or metabolic factor in the T-cell recognition of autologous but not allogenic EBV-LCL.

Anal Biochem, 1987 Jul, 164(1), 207 - 13
Methods for DNA extraction from Candida albicans; Glee PM et al.; Three different methods are described for the extraction of total genomic DNA from the dimorphic fungus Candida albicans . One method, which enables a large number of cultures to be processed simultaneously, involves pulverizing dried cells with glass beads and then allowing the disrupted cells to break apart, autolyse, by incubation in a solution which includes sorbitol and a nonionic detergent . DNA extraction by a second method with a French pressure cell can be utilized on cultures in any phase of growth, but is not practical for processing numerous samples . The third method, which involves induction of spheroplasts, is commonly used for DNA extraction from various yeasts but is not suited for processing many samples simultaneously . The DNA extracted with the three procedures is comparable in quality; in particular, it is of high molecular size (greater than 30 kbp) and reacts readily with DNA-modifying enzymes such as restriction endonucleases.

Proc Soc Exp Biol Med, 1987 Jul, 185(3), 325 - 34
Characterization with crossed immunoelectrophoresis of some antigens differentiating a virulent Candida albicans from its derived, avirulent strain; Calderone R et al.; Antigenic differences between a wild-type virulent Candida albicans 4918 (wt) and its spontaneous avirulent mutant (m-10) were found with crossed immunoelectrophoresis . Yeast cell extracts as well as soluble protein and mannoprotein fractions obtained by affinity chromatography on concanavalin A (Con A) were analyzed . Sera from patients with candidiasis and antisera from rabbits infected with live wt cells and boosted with wt extracts or rabbits immunized with purified wt cell wall preparation were used as counter reactants . Qualitative differences in serum precipitins formed by patients with suspected or culture-proven candidiasis to polysaccharide antigens of wt and m-10 origin were observed . In comparison, except for a spike-formed precipitate detected only with the wt extract, the serum from infected rabbits precipitated the wt and m-10 cell wall polysaccharide antigens about equally . The same type of precipitate was also found with the Con A wt mannoprotein fractions but was again lacking with the m-10 mannoproteins . This precipitate, with extremely slow electromobility in the first dimension, may be related to some special immunodeterminant of the wt mannan molecule . No substantial differences in the precipitation patterns of the Con A wt and m-10 proteins were found when analyzed with patients' sera or rabbit anti-cell sera . However, using these protein fractions with anti-cell wall sera revealed a larger number of precipitates for the wt as opposed to the m-10 strain . The observed antigenic differences between the virulent- and the avirulent-derived strains seem to be mainly associated with cell wall determinants (components) and might be related to the greater adherence and infectivity of the wild strain.

Klin Monatsbl Augenheilkd, 1987 Jun, 190(6), 496 - 500
{Animal experiment model of keratomycosis}; Behrens-Baumann W et al.; A model of experimental keratomycosis in the rabbit eye is described . Candida albicans strain DSM 70010 (10 microliters; 2.5 X 10(5) cells) is injected intracorneally without employing immunosuppressive measures . This strain is characterized by marked germ-tube formation, which apparently is a major cause of its virulence . All 17 eyes developed an infiltration of the cornea two days after injection . On Day 6 (mean value; standard error +/- 2.34 days) this infiltration developed synchronously to a severe corneal ulcer with hypopyon . The infection remained active for about two weeks and was either complicated by a descemetocele or perforation or led to a reparatory stage with extensive vascularization and successive leukoma . The model presented is reproducible for the first time and is therefore recommended for experimental evaluation of new therapeutic concepts.

Int J Dermatol, 1987 Jun, 26(5), 314 - 9
Systemic candidiasis in heroin abusers . Cutaneous findings; Bielsa I et al.; Systemic candidiasis in intravenous drug abusers (IVDA) is a new syndrome caused by Candida albicans and characterized by the sequential development of skin, eye, and osteoarticular lesions, which together form a typical clinical picture . We studied 30 patients with suggestive skin lesions: papules, nodules, and pustules in hair-bearing areas, particularly the scalp and beard area, associated with hair invasion by candidal hyphae . Ocular and osteoarticular involvement and presence of candidemia in some of the patients suggested blood-borne colonization of C . albicans . The infection has been related to "brown" heroin . The origin of C . albicans and the reasons for its exclusive localization in the skin and these organs are discussed . The characteristic clinical picture is widely different from that of classic disseminated candidiasis in immunodeficient patients . Therapy is also discussed.

J Med Chem, 1987 Jun, 30(6), 1054 - 68
Synthesis and oral antifungal activity of novel azolylpropanolones and related compounds; Ogata M et al.; To find orally active antifungal agents, novel imidazolyl- and 1,2,4-triazolylpropanolones I and related compounds II-IV were synthesized . Compounds I were derived from ketones V (method A), alpha-diketone IX (method B), alpha-hydroxy ketones X (method C), alpha-chloro ketone XII (method D), and enones VI (method E) . Diols II, synthesized from I with NaBH4, were cyclized to five-membered cyclic compounds III by using N,N'-carbonyldiimidazole, thionyl chloride, N,N'-(thiocarbonyl)diimidazole, bromochloromethane, 2,2-dimethoxypropane, and cyclohexanone dimethyl ketal . Diols IV were synthesized from I by Grignard reaction (method F), hydroxymethylation of X (method G), and reaction of ketones XXI with 1-{(trimethylsily)methyl}-1,2,4-triazole (method H) . Compounds I-IV were examined for their antifungal activities in vitro by evaluation of broth dilution MIC values against three species of fungi and the inhibitory effect on pseudomycelium of Candida albicans, and they were examined for oral efficacy in vivo against subacute systemic candidiasis in mice and superficial dermatophytosis in guinea pigs . Compounds 2, 12, 38, 39, and 92 exhibited strong oral antifungal activity . An asymmetric synthesis and the structure-activity relationships of the compounds examined are discussed.

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