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Antimicrob Agents Chemother, 1985 May, 27(5), 692 - 4 Inhibitory effects of chlorpromazine on Candida species; Wood NC et al.; Chlorpromazine was tested for antifungal activity by using Candida albicans and standard assays . The MIC of chlorpromazine was 35 micrograms/ml; the minimal fungicidal concentration was also 35 micrograms/ml . The minimal effective concentration was 2.2 to 3.5 micrograms/ml (using assays based on quantitative cultures and growth) . There was a slight positive interaction between chlorpromazine and amphotericin B but no interaction between chlorpromazine and rifampin . Chlorpromazine also inhibited C . krusei, C . parapsilosis, C . tropicalis, and Torulopsis glabrata . We conclude that phenothiazines have direct anti-Candida activity and that these drugs appear to have a broad antimicrobial spectrum. Ann Inst Pasteur Microbiol, 1985 May-Jun, 136A(3), 371 - 80 A replica plating technique for in vitro study of susceptibility of Candida albicans to miconazole, econazole and ketoconazole: some data for standardization; Sanchez-Sousa A et al.; We report our studies in vitro on the activity of ketoconazole (KZ), econazole and miconazole on 115 isolates of Candida albicans of clinical origin tested by an agar dilution method with three different culture media: yeast morphology agar, Sabouraud maltose agar and Casitone agar (CA) . The antifungal effects of the imidazole compounds (IC) were strongest in CA . Eighty percent of the strains were inhibited by 0.1 micrograms/ml of KZ, the most active drug . The frequent appearance of "veil growth" at higher concentrations of the IC made the exact determination of the minimal inhibitory concentration (MIC) difficult . Microscopic examination of the growth on plates at the highest drug dilutions was performed and the results compared with a replica plating technique of IC plates on other plates with antibiotic-free media . The following were observed: a) a residual capacity of cell division of Candida strains even in the presence of high antifungal concentrations to which they are considered sensitive; and b) a certain viability (7% of the cases) of some fungal cells in the residual growth, particularly in those strains with higher conventional MIC . A standardized methodology is needed for the clinical evaluation of the susceptibility tests of Candida to the imidazolic compounds. Zh Mikrobiol Epidemiol Immunobiol, 1985 May, (5), 86 - 9 {Production of a factor inhibiting macrophage migration to the Candida albicans antigen in mice and their resistance to this microorganism}; Vorob'ev KV et al.; Resistance to C . albicans, an opportunistic microorganism, has been studied in CBA and C57BL/6 mice, oppositely responsive in the production of the factor inhibiting migration of macrophages to antigen obtained from this fungus . The study has shown that CBA mice, highly responsive in the macrophage migration inhibiting factor, are less resistant to C . albicans, while C57BL/6 mice with low response to this antigen are more resistant to this infective agent . Macrophages play, probably, a certain role in the generalization of the process because not all phagocytized C . albicans cells are digested. J Gen Microbiol, 1985 May, 131 ( Pt 5), 1217 - 21 A comparison of phospholipase activity, cellular adherence and pathogenicity of yeasts; Barrett-Bee K et al.; Phospholipase A and lysophospholipase activities were measured in the culture fluid and in the blastospores of Candida albicans . When phospholipase activity was measured in six yeasts (four strains of C . albicans and a single strain each of Candida parapsilosis and Saccharomyces cerevisiae) a correlation was found between this activity and two potential parameters of pathogenicity . The C . albicans isolates which adhered most strongly to buccal epithelial cells and were most pathogenic in mice had the highest phospholipase activities . Non-pathogenic yeasts, including C . albicans isolates which did not adhere and did not kill mice, had lower phospholipase activities. Eur J Respir Dis, 1985 May, 66(5), 327 - 32 A quantitative and qualitative study of blood monocytes in smokers; Nielsen H; The effect of cigarette smoking on blood monocyte count and selected functions of isolated blood monocytes was studied in 82 subjects free of intercurrent or chronic disease, 41 smokers and 41 non-smokers . Total leukocyte counts and monocyte counts were higher in smokers than in non-smokers . In vitro functional studies of spontaneous migration, chemotactic responsiveness and phagocytosis showed no correlation with smoking habits . However, intracellular killing of Candida albicans was significantly lower in blood monocytes of smokers as compared to non-smokers . Since blood monocytes are the precursors of tissue macrophages the defective microbicidal function may represent an additional pathogenic factor in the diminished host defence observed in smokers. Antimicrob Agents Chemother, 1985 May, 27(5), 712 - 4 Effects of aminoglycoside antibiotics on polymorphonuclear leukocyte function in vivo; Venezio FR et al.; In vitro incubation of aminoglycoside antibiotics with human polymorphonuclear leukocytes (PMNs) has been shown to induce abnormalities in cell function . This study was designed to determine whether there are similar abnormalities in leukocyte function after exposure to the action of these agents in vivo . Four aminoglycosides (gentamicin, tobramycin, netilmicin, and amikacin) were tested . In vitro incubation did not induce a chemotactic defect when measured by an under-agarose method . However, inhibition of candidacidal activity was reproducible after in vitro incubation of all aminoglycosides tested . Nevertheless, when the aminoglycosides were administered intravenously to normal volunteers, PMN function, including adherence to nylon wool columns, chemotaxis, phagocytosis, and killing of Candida albicans, was unimpaired at 1, 3, and 24 h postinfusion . Therefore, we conclude that aminoglycoside antibiotic administration does not induce PMN dysfunction in vivo. Clin Exp Immunol, 1985 May, 60(2), 303 - 10 A non-specific inhibitor produced by Candida albicans activated T cells impairs cell proliferation by inhibiting interleukin-1 production; Lombardi G et al.; Human T lymphocytes cultured in vitro for 5 days with Candida albicans purified polysaccharide (MPPS) produce and antigen non-specific inhibitor (nsINH) which blocks cell proliferation when added at the beginning of the culture . The antigen presenting function of antigen pulsed adherent cells (macrophages) is significantly impaired by incubation in nsINH . Further analysis shows that nsINH blocks the production of interleukin-1 both from human mononuclear cells stimulated with lipopolysaccharide . Furthermore, the production of interleukin-2 (IL-2) is also suppressed when MPPS stimulated cells are cultured in presence of nsINH . However nsINH does not affect the appearance of IL-2 responsive cells as the addition of gibbon IL-2 to the culture fully reverses the suppressive effect of nsINH on blast transformation. Diagn Microbiol Infect Dis, 1985 May, 3(3), 233 - 42 Opsonic activity of MCP-1 and MCP-2, cationic peptides from rabbit alveolar macrophages; Fleischmann J et al.; MCP-1 and MCP-2, cationic peptides derived from rabbit alveolar macrophages, enhanced the ability of these cells to ingest Staphylococcus aureus, Klebsiella pneumoniae, Bordetella bronchiseptica, and Candida albicans in vitro . The opsonic effect of MCP-1 was potentiated by Ca++ and Mg++ and was associated with binding of the peptide to alveolar macrophages and microorganisms . MCP-1 and MCP-2 may contribute to the ability of alveolar macrophage to ingest microorganisms that gain entry to the lower respiratory tract. J Bacteriol, 1985 May, 162(2), 826 - 9 Chitin synthase in Candida albicans: comparison of digitonin-permeabilized cells and spheroplast membranes; Georgopapadakou NH et al.; The treatment of Candida albicans (yeast form) with digitonin or dimethyl sulfoxide permeabilized cells and caused the activation of chitin synthase in situ . Endogenous activation was completely prevented by the sulfhydryl reagents N-ethylmaleimide, p-chloromercuribenzoate, and 5,5'-dithiobis(2-nitrobenzoic acid); partially prevented by the protease inhibitors antipain, leupeptin, and N alpha-tosyl-L-lysyl chloromethyl ketone; and also partially prevented by EDTA . Thus, a clostripain-like protease may be involved in the endogenous activation phenomenon . The pH activity profile, cofactor requirements, and kinetic parameters of the endogenously activated chitin synthase were identical to those of the trypsin-activated enzyme in protoplast membranes. Infect Immun, 1985 May, 48(2), 433 - 8 Individual evolution of digestive tract colonization of holoxenic mice by Candida albicans; Walbaum S et al.; Oral administration of various concentrations of Candida albicans to 6-day-old mice established colonization of the digestive tract without mortality . After being weaned (day 21), the development of colonization was studied in a group of mice by daily counting of the number of CFU contained in the feces of each animal . Two features concerning the development of colonization were noted . The course of colonization in individual mice was highly erratic and lead to either transitory or sometimes long-lasting colonization . These results show the importance of a dynamic study of colonization, a condition necessary for any experimental study. Antimicrob Agents Chemother, 1985 May, 27(5), 832 - 5 Activity of UK-49,858, a bis-triazole derivative, against experimental infections with Candida albicans and Trichophyton mentagrophytes; Richardson K et al.; The therapeutic potential of UK-49,858, a difluorophenyl bis-triazole derivative, has been assessed by evaluating its activity against systemic infections with Candida albicans in normal mice and rats and in mice with impaired defence mechanisms, against vaginal infections with C . albicans in mice, and against dermal infections with Trichophyton mentagrophytes in guinea pigs . Orally administered ketoconazole was used as a comparative agent throughout, and parenterally administered amphotericin B was included in the study of C . albicans systemic infection in normal mice . The activity of UK-49,858 given orally to mice or rats infected systemically with C . albicans was far superior to that of ketoconazole . In addition, UK-49,858 showed activity comparable to that of amphotericin B when given parenterally, although the latter gave more prolonged protection . UK-49,858 was also effective orally in curing experimental candidal vaginitis in mice and trichophytosis in guinea pigs, against which it was approximately 10 times more active than ketoconazole . These data suggest that UK-49,858 may be of value in the treatment of both C . albicans and dermatophyte fungal infections in man. Biochim Biophys Acta, 1985 Apr 29, 828(3), 247 - 54 Synthetic derivatives of N3-fumaroyl-L-2,3-diaminopropanoic acid inactivate glucosamine synthetase from Candida albicans; Milewski S et al.; Synthetic derivatives of N3-fumaroyl-L-2,3-diaminopropanoic acid constitute the novel group of glutamine analogs . They are powerful, competitive inhibitors of the glucosamine synthetase (2-amino-2-deoxy-D-glucose-6-phosphate ketol-isomerase (amino-transferring), EC 5.3.1.19) from Candida albicans with respect to glutamine and uncompetitive with respect to D-fructose 6-phosphate . Some of the compounds tested irreversibly inactivate glucosamine synthetase with Kinact values of 10(-4) to 10(-6) M . The addition of glutamine protects enzyme from the inactivation, while the absence of D-fructose 6-phosphate lowers the rate of inactivation . An ordered, sequential mechanism is suggested for binding of the inhibitors to the glutamine-binding site . A number of tested compounds act as active-site-directed, irreversible inhibitors . It is suggested that derivatives of N3-fumaroyl-L-2,3-diaminopropanoic acid should be classified as mechanism-based enzyme inactivators . Structural requirements for an effective inactivator containing N3-fumaroyl-L-2,3-diaminopropanoic acid moiety are discussed. Eur J Obstet Gynecol Reprod Biol, 1985 Apr, 19(4), 237 - 46 Candidosis of the genital tract in non-pregnant women; Gough PM et al.; PIP: This prospective study was aimed at determining the prevalence of specific signs and symptoms in nonpregnant women harboring Candida albicans in the lower genital tract . Of 300 women randomly selected from a sexually transmitted diseases clinic, 93 (31%) harbored C albicans and 1 carried C glabrata in the lower genital tract . Perineal isolations were recorded in 58 (62%) of the 94 women with Candida . 50 of the women had another genital infection . 84 (89%) of the 94 women with Candida had at least 1 moderate or marked symptom or clinical sign, predominantly vaginal discharge . Of the 300 women studied, 146 were using oral contraceptives (OCs); 51 (35%) of OC users had Candida compared with 43 (28%) of nonusers--a nonsignificant difference . Finally, the incidence of trichomoniasis, anaerobic vaginitis, and other nonspecific genital infection was lower among women with Candida than among the others . Eur J Clin Microbiol, 1985 Apr, 4(2), 98 - 101 Evaluation of the Ramco latex agglutination test in the early diagnosis of systemic candidiasis; Burnie JP et al.; The value of the Ramco latex agglutination test in the diagnosis of systemic candidiasis was determined using 225 serum samples from 30 patients with systemic candidiasis, 81 serum samples from patients colonized with Candida albicans and 400 control serum samples from hospital patients with no evidence of Candida albicans infection . Results were positive (titres greater than or equal to 1:4) in 20 of the patients with systemic candidiasis; ten had titres of 1:8 . Only one of the 81 sera from colonized patients was positive (titre greater than 1:4); this serum came from a patient with colonization of the intravenous catheter . No positive results (titres greater than 1:2) were obtained in the control sera once rheumatoid factor was excluded . The test reliably differentiated between colonization and systemic infection but failed to detect some cases of systemic infection . A poor detection rate was seen in cases where only one serum sample was taken . The importance of taking daily serum samples for continuous monitoring is emphasised . Rheumatoid factor positivity and intravenous line colonization should be excluded when interpreting a result. Acta Pathol Microbiol Immunol Scand {C}, 1985 Apr, 93(2), 49 - 52 Influence of five different anticoagulants on human blood monocyte isolation and functional activities; Nielsen H; The recovery of blood monocytes after centrifugation with metrizoate/polysucrose was high with EDTA (97.0%) and heparin (91.6%) as anticoagulants, moderate with EGTA and citrate, but low with oxalate (52.3%; P less than 0.05 compared with heparin) . There were no differences in viability, spontaneous migration, chemotaxis, or phagocytosis and killing of Candida albicans by the monocytes isolated from blood anticoagulated with heparin, citrate, oxalate, EDTA, or EGTA . However, heparin in concentrations above 20 IU/ml decreased the spontaneous migration and chemotaxis . It is concluded, that EDTA and heparin below 20 IU/ml are the most satisfactory anticoagulants for the functional study of blood monocytes isolated by metrizoate/polysucrose density centrifugation. Am J Perinatol, 1985 Apr, 2(2), 121 - 2 Prenatal diagnosis of Candida albicans chorioamnionitis; Romero R et al.; The use of diagnostic amniocentesis has been proposed for the evaluation of patients with clinical suspicion of chorioamnionitis, such as those with premature rupture of membranes and premature labor . We describe a patient in whom the diagnosis of Candida chorioamnionitis was made after diagnostic amniocentesis with the assistance of a simple and rapidly performed potassium hydroxide smear. Antimicrob Agents Chemother, 1985 Apr, 27(4), 625 - 31 Immunoadjuvant activity of amphotericin B as displayed in mice infected with Candida albicans; Bistoni F et al.; Mice receiving a single intraperitoneal injection of amphotericin B showed increased resistance to subsequent challenge with either Candida albicans or Staphylococcus aureus . This enhancement of resistance was obvious in terms of both survival criteria and clearance of the intravenously injected organism from different organs . The protective effect of amphotericin B was conditioned by dose, time of drug administration, and size of yeast or bacterial inoculum and was reversed by cyclophosphamide . Effector cells from mice treated with amphotericin B displayed enhanced fungicidal activity in vitro as measured in a short-term 51Cr release assay . Macrophages from intact animals exposed in vitro to amphotericin B also acquired strong candidacidal reactivity. J Gen Microbiol, 1985 Apr, 131 ( Pt 4), 775 - 80 Mechanism of action of nikkomycin and the peptide transport system of Candida albicans; McCarthy PJ et al.; Nikkomycin was found to be a potent growth inhibitor of Candida albicans through competitive inhibition of chitin synthase {Ki = 0.16 microM (0.1 microgram ml-1)} . The activity of the peptide-nucleoside drug was antagonized by both peptone and defined peptides . Transported dipeptides were effective antagonists while transported oligopeptides were not . A mutant of C . albicans resistant to the effects of nikkomycin through a transport defect was unable to transport dipeptides, while oligopeptide uptake was apparently unaffected . At least two peptide permeases are operational in this organism. J Immunol, 1985 Apr, 134(4), 2658 - 65 In vitro natural cell-mediated cytotoxicity against Candida albicans: macrophage precursors as effector cells; Baccarini M et al.; Bone marrow cells, cultured in L-929 CSF, consist of cells of granulocyte and macrophage lineages . Cells of the granulocyte lineage are known to be cytotoxic for Candida albicans . In this paper we report that macrophage precursor cells also display strong cell-mediated cytotoxicity against the yeast form of the dimorphic fungus C . albicans . The macrophage precursors responsible for this activity are nylon wool-nonadherent, nonphagocytic cells and lack asialo GM1 surface antigen . A purified population of macrophage precursors (greater than 95%) was obtained by means of Percoll density centrifugation . The interaction of these purified effectors with the target yeast cells was analyzed at a single cell level, and their activity was compared with that displayed by cells of the granulocytic series derived from the same bone marrow culture . Macrophage precursor cells proved to be more effective in binding the target cells and showed the same killing ability as the granulocytes: macrophage precursors were not damaged by contact with the target, in contrast to that which happened with granulocytes . In a long-term colony-forming unit assay, in fact, granulocytic cells showed a decrease over time in their ability to inhibit the growth of C . albicans, probably due to cell damage and death after the interaction with the target . In contrast, no loss of activity was observed with the macrophage precursor fraction . The same macrophage precursor cells also proved able to exert good natural killer activity against YAC-1 lymphoma cells, but not against P815 mastocytoma cells, as reported previously . The macrophage precursor cells, when cultivated in vitro to mature macrophages, lost completely their natural cytotoxicity against C . albicans and YAC-1 cells . The implications of these findings, as well as the possible role in vivo of such a precursor cell population during an infection, are discussed. Acta Pathol Microbiol Immunol Scand {C}, 1985 Apr, 93(2), 85 - 9 Phagocytosis and killing of Candida albicans by blood monocytes from patients with non-seminomatous testicular carcinoma: effect of chemotherapy; Nielsen H et al.; Blood monocytes were isolated from 14 patients with non-seminomatous testicular carcinoma and tested for phagocytic and fungicidal activity towards Candida albicans . Before chemotherapy, monocyte function in the patients was not different from that of normal controls . However, patients with alpha-foetoprotein in their serum had a lower phagocytic activity compared with patients without alpha-foetoprotein . No correlation with the histology of the tumor, the clinical stage or the presence in serum of human chorionic gonadotropin was observed . Serum from the patients had no influence on the functions of normal monocytes . During intensive chemotherapy with cisplatinum, bleomycin and vinblastine, a reversible impairment in phagocytosis and killing of C . albicans occurred which had no correlation with the development of febrilia . Two months after the completion of chemotherapy the monocyte functions were unchanged as compared with pretreatment values . In conclusion, the temporary depression of monocyte functions towards C . albicans during chemotherapy might, in addition to other risk factors, predispose the patient to fungal infection. Sabouraudia, 1985 Apr, 23(2), 107 - 18 Characterization of Candida antigens by crossed-immunoaffinoelectrophoresis; Bruneau SM et al.; The antigens of three Candida albicans strains (3153 A, 3156 B and CBS 1905) and one C . tropicalis strain were studied by means of crossed-immunoaffinoelectrophoresis with the corresponding polyvalent antisera . Most antigens (from 63.8% to 77.7% depending on the strain) were bound to concanavalin A-sepharose and about 20% to blue cibacron-sepharose for all the strains tested . Free concanavalin A, wheat germ lectin-sepharose and Helix pomatia lectin-sepharose revealed differences between C . albicans 3153 A and C . albicans CBS 1905 on the one hand and C . albicans 3156 B and C . tropicalis on the other, since affinity percentages were from 4.2 to 10.2 and from 14.2 to 20.0 respectively . Among 10 previously described species-specific antigens of C . albicans, 4 were never bound and 5 were bound to concanavalin A-sepharose which was considered an unsuitable agent for antigen purification since it retained 77% of C . albicans antigens . One important species-specific antigen was bound to blue cibacron sepharose and the corresponding purification could be undertaken . Similar results were found for 12 species-specific antigens of C . tropicalis . Blue cibacron-sepharose as well as wheat germ lectin or Helix pomatia lectin-sepharose were found suitable agents for purification of some of them. Br Med J (Clin Res Ed), 1985 Mar 9, 290(6470), 746 - 8 Outbreak of systemic Candida albicans in intensive care unit caused by cross infection; Burnie JP et al.; The first documented outbreak of systemic candidosis shown to be due to cross infection with a particular strain of Candida albicans is reported . Over nine months in an intensive care unit 13 patients developed definite and one probable systemic candidosis . Twenty five further patients had superficial candidal infections . The strain that caused the outbreak (serotype A, morphotype A1, biotype 0/(1)5 5/7) was responsible for all the cases of systemic candidosis acquired in the intensive care unit, 11 (44%) of the superficial candidal infections in the unit, and 17% of candidal infections outside the unit but in the same hospital . The strain was also isolated from oral swabs taken from four nurses working in the unit and the hands of one of these nurses . Two out of 17 nurses were shown to have acquired the strain on their hands when examined immediately after nursing systemically infected patients . No environmental source could be identified . The strain also showed enhanced survival in handwashing experiments and was relatively resistant to Hibiscrub . Management of patients with systemic candidosis might include measures to prevent cross infection and handwashing with disinfectants that are active against candida. Curr Eye Res, 1985 Mar, 4(3), 243 - 52 Studies in experimental keratomycosis; O'Day DM; The study of experimental fungal infections requires effective animal models . Two such models in the rabbit model have been developed and applied to various aspects of topical antifungal therapy . In these models, the polyenes, as a class, are superior in efficacy to the imidazoles and flucytosine, but efficacy is clearly strain related . Corticosteroids, when administered concomitantly with antifungal agents, adversely influence antifungal activity in vivo . This steroid effect is inversely proportional to the efficacy of the antifungal agent . The corneal epithelium appears to be a significant barrier to the penetration of the polyene antibiotics . Although the predictive power of in vitro susceptibility testing as a guide to in vivo efficacy is uncertain, a correlation was seen between the in vivo and in vitro effect for amphotericin B against three strains of Candida albicans. J Clin Hosp Pharm, 1985 Mar, 10(1), 79 - 88 Growth of microorganisms in total parenteral nutrition mixtures and related clinical observations; Scott EM et al.; The effect of lipid addition to TPN (Total Parenteral Nutrition) solutions on microbial growth was investigated . Staphylococcus epidermidis, which failed to grow or grew poorly in the absence of lipid, reached greater than 10(4) cfu/ml (colony forming units per ml), from an initial inoculum of approximately 50 cfu/ml after 24 h when lipid was added . Candida albicans grew more slowly in the presence of lipid, but nevertheless reached 10(4) cfu/ml after 40 h incubation . Klebsiella aerogenes grew readily in all solutions, whereas Escherichia coli failed to grow in any solution . Growth of S . epidermidis and K . aerogenes was improved when the inoculum consisted of starved cells; however, growth of starved cells of C . albicans lagged behind that of unstarved cells . The ability of S . epidermidis to grow in lipid-containing TPN mixtures is particularly important, since this organism is frequently associated with sepsis . In an infant surgical unit, where TPN is under the care of a nutrition team, samples of TPN fluids and giving sets were examined for microbiological contamination at the end of the 24 h administration period . Contamination was found in eight of the 98 systems examined from eight patients . The organisms were identified as coagulase-negative staphylococci and diphtheroids. Clin Exp Immunol, 1985 Mar, 59(3), 716 - 24 Antigens of Aspergillus fumigatus . III . Comparative immunochemical analyses of clinically relevant aspergilli and related fungal taxa; Piechura JE et al.; Cell sap (CS) of the pathogenic fungus Aspergillus fumigatus strain Ag-507 was fractionated by Sephadex G-200 column chromatography . A protein fraction designated CS3 was partially characterized by two dimensional electrophoresis (2-DE) and analytical ultracentrifugation . CS3 consisted mainly of low molecular weight components (14 K-43 K) of the whole CS, and produced one peak in analytical ultracentrifugation with an Sapp of 4.25 . CS3 was demonstrated to be different from a previously characterized CS fraction designated as CS2, by 2-DE, and by CS2 and CS3 specific antisera . CS3 gave precipitin reactions with three aspergilloma patient sera and 100% of sera from allergic bronchopulmonary aspergillosis (ABPA) patients . Significantly, three ABPA patient sera reacted with CS3 and not CS2 . The CS of A . fumigatus strains Ag-515 and Ag-534, were also examined for the presence of CS3 components as were CS preparations of five additional Aspergillus species; A . flavus, A . fischeri, A . terreus, Neosartorya (Aspergillus) fennelliae, and A . niger, and three fungal taxa; Penicillium notatum, Candida albicans, and Saccharomyces cerevisiae . 2-DE, immunoelectrophoresis and double diffusion (DD) analyses of the CS preparations provided complementary information . The immunochemical similarity of CS2 and CS3 components of different aspergilli appears to reflect the taxonomic relatedness of the aspergilli . Additionally, aspergilli exhibiting CS2 and CS3 components most similar to A . fumigatus strain Ag-507 are more frequently isolated from aspergillosis patients . There may be an association of these components with incidence of involvement of the organisms in aspergillosis . DD analysis of the cross-reactivity of CS of all taxa with ABPA and aspergilloma patient sera supported the 2-DE and absorption data. Nurs Clin North Am, 1985 Mar, 20(1), 227 - 34 Symposium on infections in the compromised host . The leukemias; Newman KA; The treatment of acute leukemia in the adult causes prolonged and profound granulocytopenia . When the patient has less than 100 granulocytes per microliter, the risk of life-threatening infection is extremely high . Major infections include bacteremia, pneumonia, pharyngitis, esophagitis, colitis, perianal or perirectal lesions, and cellulitis . The major organisms are gram-negative bacilli (especially Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae), gram-positive organisms (Staphylococcus epidermidis and Staphylococcus aureus), the yeasts (Candida albicans and Torulopsis glabrata), and the filamentous fungi (Aspergillus flavus and fumigatus) . Infection prevention includes the return to normal of the patient's host defense mechanisms, reduction of invasive procedures which breach body barriers, and methods to decrease the acquisition of potential pathogens, and to reduce the number of organisms colonizing the patient. J Gen Microbiol, 1985 Mar, 131 ( Pt 3), 505 - 13 Killing of yeast, germ-tube and mycelial forms of Candida albicans by murine effectors as measured by a radiolabel release microassay; Baccarini M et al.; Candida albicans undergoes yeast to mycelial conversion under both in vivo and in vitro conditions but the relative pathogenicity of the two forms of growth is still unknown . By adapting a recently developed 51Cr radiolabel release assay, we have quantified the killing ability of different murine effector cell populations for the hyphal form of C . albicans . Up to 50% of specific 51Cr release from the mycelial form could be detected after incubation for only 1 h, with no requirement for opsonization, provided that appropriate effector: target cell ratios were used . The specific 51Cr release correlated well with viability, as assessed by dye exclusion tests, and with pathogenicity potential in cyclophosphamide-immunodepressed mice . Comparison of the activity of different murine effectors against yeast and hyphal forms showed that hyphal forms were killed by murine effectors to a similar, if not greater, extent than yeast forms . In particular, thioglycollate-induced murine polymorphonuclear neutrophils were able to kill hyphal cells extracellularly and without an opsonic requirement. J Gen Microbiol, 1985 Mar, 131 ( Pt 3), 495 - 503 Extracellular polymer of Candida albicans: isolation, analysis and role in adhesion; McCourtie J et al.; Extracellular polymeric material (EP) was isolated from culture supernatants of Candida albicans grown on carbon sources (50 mM-glucose, 500 mM-sucrose or 500 mM-galactose) known to promote yeast adhesion to different extents . Galactose-grown yeasts, which are the most adherent, produced more EP than sucrose-grown organisms, particularly after incubation for 5 d, while glucose-grown yeasts (the least adherent) gave the lowest yield . EP produced on all three carbon sources was of similar composition and contained carbohydrate (65 to 82%; mannose with some glucose), protein (7%), phosphorus (0.5%) and glucosamine (1.5%) . Serological studies indicated that these EP preparations were immunologically identical but that galactose-grown yeasts had more antigenic determinants than sucrose-grown organisms while glucose-grown yeasts had the fewest determinants . Antigenic differences were apparent between EP preparations of some strains of C . albicans . Pretreatment of acrylic strips with EP to form a polymeric coating promoted yeast adhesion to the acrylic surface, but similar pretreatment of buccal epithelial cells with EP inhibited subsequent yeast adhesion . These results indicate that EP originates from the cell surface of C . albicans and that it contains the surface component(s), probably mannoprotein in nature, responsible for yeast adhesion. J Antimicrob Chemother, 1985 Mar, 15(3), 263 - 9 Chemical and antigenic alterations of Candida albicans cell walls related to the action of amphotericin B sub-inhibitory doses; Al-Bassam T et al.; Sub-inhibitory doses of amphotericin B led to Candida albicans cell wall modifications which involved peptidomannans . The amount of this product was reduced by a third, the decrease being due to mannans whose absolute and relative values fell whereas the amount of amino-acids increased . Concomitantly, the treated cells exhibited a loss in their immunological reactivity. J Oral Rehabil, 1985 Mar, 12(2), 177 - 82 The effectiveness, in vitro, of miconazole and ketoconazole combined with tissue conditioners in inhibiting the growth of Candida albicans; Quinn DM; Two recent antifungal agents, miconazole and ketoconazole, were combined with three tissue conditioners and tested in vitro for their effects on the growth of Candida albicans . Studies for comparison were carried out using the earlier antifungal agents, amphotericin B and nystatin . Miconazole and ketoconazole were as effective as nystatin in completely inhibiting the growth of Candida albicans . The ineffectiveness of amphotericin B when combined with tissue conditioners as an antifungal agent was confirmed . (See Addendum p.181.). J Bacteriol, 1985 Mar, 161(3), 1131 - 6 Instability of Candida albicans hybrids; Whelan WL et al.; Total cellular DNA content, determined by a colorimetric method, was used as an index of ploidy in Candida albicans . Mononucleate hybrids were formed by fusion of spheroplasts derived from diploid parent strains . Five hybrids, of six studied, were taken to be tetraploid on the basis of estimated DNA content . One hybrid was taken to be hexaploid or near-hexaploid . Selection for increased resistance to 5-fluorocytosine in the hybrids, which were heterozygous for resistance, resulted in isolation of variants which were of lower ploidy than the hybrids from which they originated . Variants were obtained which corresponded (in measured DNA content) to aneuploid, triploid, and diploid states . These results may form the basis of a cyclic parasexual system (2n X 2n----4n----2n) for genetic analysis of this asexual species. J Med Chem, 1985 Mar, 28(3), 278 - 81 Synthesis of new polyoxin derivatives and their activity against chitin synthase from Candida albicans; Emmer G et al.; Two analogues of L-alanylpolyoxin C with a modified peptide bond were synthesized and tested for inhibition of chitin synthase in Candida albicans . N-Methylation of the peptide bond (compound 13) or the replacement of it by NH2CH2 (compound 9) led to loss of activity in the enzyme assay . A novel analogue (compound 5) of nikkomycin was synthesized from uracil polyoxin C and (2S,3R)-3-hydroxyhomotyrosine, a component of echinocandin C . Despite high activity in the chitin synthase assay, 5 had no inhibitory effect on cells of C . albicans. J Allergy Clin Immunol, 1985 Mar, 75(3), 388 - 94 Induction of antigen-specific suppressor cells in patients with hay fever receiving immunotherapy; Nagaya H; In order to evaluate the effect of immunotherapy on subpopulations of lymphocytes, peripheral blood mononuclear cells were fractionated into T and non-T cells by incubating in anti-immunoglobulin-coated plates . T cells were further fractionated into rye grass antigen-adherent and nonadherent fractions and human serum albumin (HSA)-adherent and nonadherent fractions by incubating in rye grass antigen-coated and HSA-coated plates, respectively . The mean rye antigen-stimulated proliferative response of rye antigen-adherent fraction was significantly lower than that of rye antigen-nonadherent fraction in patients with rye grass hay fever receiving immunotherapy . There was no difference in the rye antigen-stimulated proliferative response between the HSA-adherent and nonadherent fractions . Both the rye antigen-adherent and nonadherent fractions proliferated similarly when they were stimulated by an unrelated antigen, Candida albicans . The rye antigen-stimulated proliferative response of rye antigen-nonadherent cells could be suppressed by coculturing with rye antigen-adherent cells from patients receiving immunotherapy . Furthermore, the treatment of cocultures with monoclonal antibody against suppressor-cytotoxic T cell (OKT8) subpopulation and guinea pig serum complement reversed the suppression . In patients receiving no immunotherapy, there was no difference in the rye grass antigen-stimulated proliferative response between the rye antigen-adherent and nonadherent fractions . These results suggest that immunotherapy induces a subpopulation of T cells that are adherent to antigen-coated plates and are capable of suppressing T cell proliferation stimulated by the specific antigen. J Immunol Methods, 1985 Feb 11, 76(2), 247 - 53 A flow cytometric method for the measurement of phagocytosis by polymorphonuclear leucocytes; Wilson RM et al.; A new method for the measurement of phagocytosis of Candida albicans by human polymorphonuclear leucocytes (PMN) is described using a fluorescence activated cell sorter . We have used acridine orange to discriminate between PMN which have internalised yeast particles and those which have not . This method allows accurate measurement of particle phagocytosis as an event distinct from particle adherence . It also permits detailed examination of the kinetics of phagocytosis, the study of which is likely to be of value in the investigation of diseases where abnormalities of PMN function are suspected. Antimicrob Agents Chemother, 1985 Feb, 27(2), 252 - 6 Specific inhibition of fungal sterol biosynthesis by SF 86-327, a new allylamine antimycotic agent; Ryder NS; SF 86-327 is a new antimycotic agent of the allylamine type . Its primary action appears to be the inhibition of ergosterol biosynthesis at the point of squalene epoxidation, as was previously found with the related compound naftifine . Biosynthesis was measured by incorporation of {14C}acetate into sterols in cells of Candida albicans, Candida parapsilosis, Torulopsis glabrata, and the dermatophyte Trichophyton mentagrophytes . There was a positive correlation between the SF 86-327 concentrations needed for inhibition of growth and of sterol synthesis in these four fungi . The greater antifungal efficacy of SF 86-327 in comparison with naftifine was also reflected in the relative activities of the two compounds as sterol synthesis inhibitors . Inhibition was maximal at neutral pH . A similar degree of inhibition was found in cell-free extracts when {14C}mevalonate was used as substrate . In all cases, inhibition of sterol synthesis was accompanied by a parallel accumulation of labeled squalene . SF 86-327 and naftifine had no significant effect on initial enzymes of the ergosterol pathway, measured by incorporation of {14C}acetyl coenzyme A, or on steps distal to squalene epoxidation, measured by conversion of labeled squalene 2,3-epoxide or lanosterol . Both allylamines were highly selective for fungal, as opposed to mammalian, sterol biosynthesis . SF 86-327 caused slight inhibition of squalene epoxidation in a rat liver cell-free system, but at concentrations three to four orders of magnitude greater than those required for inhibition of the fungal pathway. Zentralbl Bakteriol Mikrobiol Hyg {B}, 1985 Feb, 180(2-3), 155 - 64 {Prevention of mycoses caused by yeasts}; Seeliger HP; The wide-spread ubiquitous occurrence of molds and great masses of aerial spores (conidia, arthrospores etc.) as well as of yeast species with facultative pathogenicity, renders prophylaxis of respective human infections caused by such opportunists, rather difficult . Suppression of such fungi and continuous surveillance of endangered patients require considerable efforts and costs . Adequate control is particularly cumbersome in Candida infections, since the causative yeasts may be considered as "normal" commensals of the mucous membranes in many individuals . Overt secondary infections are frequently of endogenous origin, hence the name "endomycoses" as introduced by Gemeinhardt (1976) . Under particular conditions such as care for patients with extended burns, or patients after bone-marrow transplantation or irradiation of the whole body, or patients after joint surgery, the complete elimination of yeasts is just as essential as the antibacterial decontamination over a limited period of time . In other groups of individuals similar drastic measures of control against Candida albicans are not deemed necessary . Reduction of local Candida cell counts to amounts below the individual level of tolerance may be deemed sufficient . Since the level of tolerance is, however, extremely low in infants and in many patients of the intensive care wards, especially in cases of malignant immunocytomas and leukemias of various nature, prophylaxis by proper hygienic measures and eventual preventive antimycotic treatment is an integral part of proper control. Sabouraudia, 1985 Feb, 23(1), 55 - 61 Intravenous miconazole therapy for experimental keratomycosis in rabbits; Ishibashi Y et al.; Intravenous miconazole (90 mg daily for 3 weeks) reduced the intensity of experimental fungal keratitis due to Candida albicans in a group of 10 rabbits . Clinical scores of affected eyes were statistically significantly lower in the treated group than in a control group of 10 untreated rabbits . All cultures of corneal scrapings were negative on 18th day after inoculation in the treated group, but four cultures were still positive on the 21st day in the control animals . Histopathological examination of eyes from treated and untreated rabbits showed great differences in the severity of inflammatory changes in the two groups. J Clin Microbiol, 1985 Feb, 21(2), 276 - 7 Isolation and detection of multiple yeasts from a single clinical sample by use of Pagano-Levin agar medium; Yamane N et al.; A total of 15,234 clinical samples were tested on modified Pagano-Levin agar medium to detect multiple yeast species within a single sample . Samples containing more than one yeast species were estimated to be 8.0% of the total . The most frequent combination of different yeasts was Candida albicans and Torulopsis glabrata. Infect Immun, 1985 Feb, 47(2), 480 - 3 Role of tetracycline in pathogenesis of chronic candidiasis of rat tongues; Allen CM et al.; Forty female Sprague-Dawley rats were randomly divided into two groups . Group 1 animals received tetracycline solution (0.1% during week 1 and 0.01% thereafter) as drinking water, as in previous studies . Group 2 animals received double-distilled demineralized water . Animals in both groups were inoculated orally with an equal number of viable, mucosally pathogenic Candida albicans organisms . After 20 weeks, inspection of the tongues showed gross lesions in 16 of the 20 animals in group 1 and 17 of the 20 in group 2 . These lesions were confirmed histologically . No significant difference in the number of lesions was noted between the two groups . However, the lesions in group 1 animals were significantly larger than those in group 2 animals . These results suggest that, given this mucosally pathogenic strain of C . albicans, the establishment of a chronic infection of the rat tongue is apparently not influenced by tetracycline-treated drinking water as administered in this study . This suggests that antibiotic exposure is not an essential factor in the pathogenesis of this lesion . A larger lesion area, however, does appear to be related to the use of tetracycline solution as drinking water. Blood, 1985 Feb, 65(2), 433 - 40 Rapid method for isolation of normal human peripheral blood eosinophils on discontinuous Percoll gradients and comparison with neutrophils; Roberts RL et al.; Previous studies on human eosinophils often have used cells from patients with hypereosinophilia syndrome or parasitosis owing to the difficulty in isolating pure populations of eosinophils from normal individuals . In the present study, human eosinophils were isolated with a purity of 97%, with 70% recovery from normal individuals with blood eosinophil counts of less than 3% . Human eosinophils are denser than neutrophils, but the range of densities of the two cell types overlap, making purification of eosinophils by density-gradient centrifugation difficult . However, if neutrophils were exposed to the chemotactic peptide (f-Met-Leu-Phe), which did not stimulate eosinophils, the neutrophils' density decreased, shifting them away from the density of eosinophils . Whole normal blood anticoagulated with EDTA was incubated at 37 degrees C for 15 minutes with 10(-6) mol/L f-Met-Leu-Phe and then layered over a discontinuous Percoll gradient (65% and 75% in diluted phosphate-buffered saline) and centrifuged at 400 g for 25 minutes at 22 degrees C . The cell layer between the 65% and 75% Percoll was collected and washed, and hypotonic lysis was used to remove erythrocytes . This cell layer contained 97.3 +/- 0.7% eosinophils (N = 8) with a yield of 4.9 X 10(4) eosinophils per milliliter of whole blood, or 70% of the total eosinophil count . The isolated eosinophils were in a quiescent state but responded to Escherichia coli endotoxin-activated serum with shape change and chemotaxis, membrane depolarization, and reduced nitroblue tetrazolium (96.0 +/- 1.0%), when stimulated with phorbol myristate acetate . In phagocytic assays, 89.3 +/- 1.3% of the eosinophils ingested Candida albicans v 96.0% +/- 1.0% of neutrophils . In contrast, the eosinophils did not respond chemotactically, alter membrane potential, or reduce nitroblue tetrazolium when treated with f-Met-Leu-Phe, and studies with f-Met-Leu-{3H}Phe showed that normal eosinophils lacked expression of receptors for f-Met-Leu-Phe . In control studies, normal eosinophils that were not exposed to f-Met-Leu-Phe during purification also failed to respond to f-Met-Leu-Phe, indicating intrinsic differences between normal eosinophils and neutrophils . Thus, exposure of whole blood to f-Met-Leu-Phe, followed by separation on Percoll is a simple method for rapid isolation of normal human eosinophils. J Cell Sci, 1985 Feb, 73, 207 - 20 Three-dimensional behaviour of mitochondria during cell division and germ tube formation in the dimorphic yeast Candida albicans; Tanaka K et al.; This study was done to correlate mitochondrial behaviour with nuclear behaviour and cell division as well as with the germ tube formation in the dimorphic yeast Candida albicans . Three-dimensional reconstruction of electron micrographs of serially sectioned cells of the three strains was used to determined the morphological and quantitative relationships between the structures . The results suggested that at the time of entry into the bud a few mitochondria fused into a single giant one, which fragmented during mitosis and resumed a single giant form before cytokinesis, and was then partitioned into two parts . This tendency was also shown during germ tube formation . Quantitative analysis has established that growth of organelles such as the nucleus and mitochondria closely followed total cell growth, the ratio of organelle volume to total cell volume being held relatively constant. Aust J Exp Biol Med Sci, 1985 Feb, 63 ( Pt 1), 53 - 63 Divergent expression of cytotoxic and microbicidal functions of rabbit alveolar and peritoneal macrophages: effects of non-specific activation and a natural microbicidal peptide, MCP-1; Sorrell TC et al.; Alveolar macrophages from NZW rabbits were intrinsically toxic to 6 xenogeneic cell lines and to Candida albicans in vitro . Macrophage-mediated candidacidal activity, but not cytostasis (inhibition of {3H} thymidine incorporation by target cells) or cytotoxicity (reduction in target cell number), was enhanced by prior injection of rabbits with Freund's complete adjuvant (FCA) . Compared with alveolar macrophages, peritoneal macrophages were less candidacidal (median C . albicans killed, 24% versus 16%, p less than 0.01) . In contrast to alveolar macrophages, peritoneal macrophages were not consistently cytostatic or cytotoxic . Only candidacidal activity was enhanced in FCA-elicited peritoneal macrophages (median C . albicans killed 28% versus 16% for resident peritoneal macrophages, p less than 0.01) . Microbicidal concentrations of a cationic peptide produced by rabbit alveolar macrophages (MCP-1, 25-100 micrograms/ml) did not inhibit growth of 4 murine cell lines in vitro . Macrophage-mediated cytostasis and cytotoxicity were not enhanced by culture with exogenous MCP-1 . Macrophage-mediated cytostasis was also unchanged in cultures containing 10(-5) 2' deoxycytidine . We conclude that rabbit macrophage populations are restricted in their expression of cytostatic and cytotoxic functions, that microbicidal activation can occur independently of cytotoxic activation and that in this system mechanisms of macrophage-mediated cytotoxicity to xenogeneic target cells are independent of MCP-1 and thymidine. Sabouraudia, 1985 Feb, 23(1), 81 - 3 Unilateral involvement of kidneys in mice infected with Candida albicans; Kwon-Chung KJ et al.; Mice injected with 10(3) cells of a virulent isolate of Candida albicans via the lateral tail vein developed frequent unilateral abnormalities of the right but not the left kidneys . Initially the number of colony forming units in the right and left kidneys were similar but the number of colonies became consistently higher in the right kidneys as the infection progressed . The frequency of unilateral involvement decreased when the inoculum size was increased to 5 X 10(3) cells . These observations indicate that when growth of C . albicans in vivo is monitored over a period of time starting with a low inoculum, it is critical to be consistent in culturing kidneys from the same side. Sabouraudia, 1985 Feb, 23(1), 63 - 8 Germ tube-forming cells of Candida albicans are more susceptible to clotrimazole-induced killing than yeast cells; Niimi M et al.; Yeast and germ tube-forming cells of Candida albicans were compared with respect to their susceptibility to killing induced by the imidazole antifungal clotrimazole . Cultures consisting largely of germ tube-forming cells or exclusively yeast cells were prepared by incubating cells of a germ tube-proficient strain in a proline-containing phosphate buffer at 37 degrees C or 25 degrees C, respectively . When treated with clotrimazole at 37 degrees C, the cultures of germ tube cells lost colony-forming ability much more rapidly than those of yeast cells . However, this difference was diminished in the cells preincubated at 37 degrees C but prevented from forming germ tubes by 5 mM cysteine, a suppressor of germ tube formation . In another C . albicans isolate showing a very poor capacity to form germ tubes at 37 degrees C, such a difference in killing rate was much smaller than that for the germ tube-proficient strain . Furthermore, when an isogenic pair of strains, one proficient and the other deficient in germ tube formation, were compared with each other, germ tube-forming cultures of the former were found to be more sensitive than yeast cell cultures of the latter . It is inferred from these results that the germ tube-forming cell of C . albicans is more sensitive to clotrimazole-induced killing than the yeast cell. Sabouraudia, 1985 Feb, 23(1), 47 - 54 Secreted phospholipases of the dimorphic fungus, Candida albicans; separation of three enzymes and some biological properties; Banno Y et al.; Several phospholipases are secreted into the culture medium by growing yeast cells of Candida albicans 3125 . DEAE-Sephadex column chromatography of concentrated culture filtrate revealed three separable fractions with phospholipase activities . Analysis of products of hydrolysis showed that the enzyme activities were lysophospholipase, lysophospholipase-transacylase and a phospholipase B. Mycopathologia, 1985 Feb, 89(2), 113 - 8 Immune responses elicited by vaccinations with Candida albicans ribosomes in cyclophosphamide treated animals; Segal E et al.; This study describes humoral and cell mediated immune (CMI) responses detected in cyclophosphamide (CY) treated animals who were vaccinated with Candida albicans ribosomes and were protected against systemic candidiasis (previous study) . Mice treated with CY and vaccinated with C . albicans ribosomes revealed CMI responses towards the ribosomes as measured in vivo by the foot pad swelling test and in vitro by the lymphocyte transformation assay . Both reactions were higher in CY treated and ribosome vaccinated mice than in controls (mice that were only vaccinated) . Humoral immune responses were measured by the enzyme linked immunosorbent assay (ELISA) . Anti ribosomal antibody titer contrary to the CMI responses was lower in CY treated animals than in non treated controls . These data point to a possible explanation of the mechanisms underlying the ribosomal vaccinations in CY treated hosts, and show the potential of such vaccinations in compromised individuals. Photodermatol, 1985 Feb, 2(1), 3 - 9 Propionic acid-derived non-steroidal antiinflammatory drugs are phototoxic in vitro; Ljunggren B; Clinical photosensitivity reactions have been reported for several non-steroidal antiinflammatory drugs (NSAID) . 11 such commercial preparations were studied spectrophotometrically and assayed for phototoxicity using 2 in vitro methods . Photohemolysis of human red blood cells was measured following exposure to longwave (UVA) and medium-wave (UVB) ultraviolet radiation . Growth inhibition of Candida albicans was assayed after exposure to drug and UVA . A majority of the drugs were phototoxic . Propionic acid-derived NSAIDs were the most active in the photohemolysis assays as well as in the Candida test . With UVA 43.2 J/cm2 ketoprofen was one order of magnitude more potent that the other compounds; with increasing UVB doses and a standard drug concentration of 10 micrograms/ml the same was true for benoxaprofen . Several compounds were protective against UVB hemolysis . Candida growth inhibition was strongest with naproxen . Again, propionic acid derivatives generally were the more effective . No photoactivity was noted for indomethacin, piroxicam and sulindac . Azapropazone caused UVA hemolysis only . Members of the NSAID group, and in particular derivatives of propionic acid, are capable of inducing phototoxic reactions with UVA as well as UVB in vitro . These results confirm clinical reports of photoreactions to members of this group. J Dent Res, 1985 Feb, 64(2), 122 - 5 The prevalence and significance of yeasts in persons wearing complete dentures with soft-lining materials; Wright PS et al.; Fifty-three persons wearing soft-lined mandibular dentures and heat-cured acrylic-resin maxillary dentures were studied, using imprint cultures, to determine the isolation frequency and density of colonization of denture and mucosal surfaces by yeasts . Yeasts were isolated from 35 (66%) of the persons studied . Nine species of Candida and one each of Trichosporon and Saccharomyces were identified . Candida albicans, occurring either alone or together with another strain, was identified in 66% of the isolates and was associated with a higher mean density/cm2 than that of other strains . An association between the method of denture cleaning, denture hygiene, and smoking habits and the isolation of yeasts was demonstrated, but a similar association could not be demonstrated with the sex of the person, denture-wearing habits, type and condition of the soft lining, or the clinical appearance of the mandibular denture-bearing mucosa . Although yeasts are more likely to colonize soft-lining materials than the fitting surface of conventional lower dentures, their presence did not significantly affect the soft-lining material . Further, the increased isolation of yeasts on the fitting surface of the soft-lined mandibular denture was not associated with an increased incidence of inflammatory changes in the mandibular denture-bearing mucosa. Gynecol Oncol, 1985 Feb, 20(2), 170 - 6 Monocyte function in cervical carcinoma: plasma inhibitor of monocyte chemotaxis; Lawton JW et al.; Blood monocyte function was tested in 43 untreated patients with carcinoma of the cervix (stages Ib to IIIb) and 50 age-matched controls . Monocyte counts, adhesion to glass, spreading on glass, phagocytosis and killing of Candida albicans, and chemotaxis under agarose were not significantly different between the patient and control groups . In 65% of a further series of 17 patient/control pairs, the plasma of cervical carcinoma patients was shown to contain a cell-directed inhibitor of monocyte chemotaxis . The accumulated evidence indicates that production of such factors by malignant tumors is an important mechanism in counteracting mononuclear phagocyte defense. J Bacteriol, 1985 Feb, 161(2), 781 - 3 Characterization of a tetraploid derivative of Candida albicans ATCC 10261; Hubbard MJ et al.; A morphometric analysis of Candida albicans yeast cells utilizing scanning electron microscopy showed that the cell volume and the DNA content of a tetraploid strain (derived by cell fusion) were 2.4 to 3.0 and 2.0 times, respectively, those of the progenitor diploid strain, ATCC 10261 . The pathogenicities of both strains were similar. Proc Natl Acad Sci U S A, 1985 Feb, 82(4), 1050 - 3 Parathymosin alpha: a peptide from rat tissues with structural homology to prothymosin alpha; Haritos AA et al.; A peptide, parathymosin alpha, containing approximately equal to 105 amino acid residues, has been isolated from rat thymus, and the sequence of the first 30 residues at the NH2 terminus has been determined . In this region, it shows 43% structural identity with thymosin alpha 1 and prothymosin alpha . The common sequences do not include residues 2-9, which accounts for the poor reactivity of parathymosin alpha with an antibody directed against this epitope in thymosin alpha 1 . Parathymosin alpha appears to modulate the action of prothymosin alpha in protecting sensitive strains of mice against opportunistic infection with Candida albicans. J Immunol, 1985 Feb, 134(2), 1166 - 71 Effect of glucocorticoids on the development of suppressive activity in human lymphocyte response to a polysaccharide purified from Candida albicans; Piccolella E et al.; The action of glucocorticoids on the proliferative response of human lymphocytes stimulated in vitro by MPPS has been investigated . The effect of Dex was dependent on the time of steroid addition to the cultures . Dex added at the beginning of the culture period inhibited, cell proliferation and IL 1/IL 2 synthesis, although not completely . However, a delayed addition of 24 to 48 hr resulted in an enhancing effect on cell proliferative responses that was maximal at day 4 . The effect of Dex on T suppressor cell activity was then investigated . Dex added 1 day before the appearance of suppressor cells resulted in a marked decrease or disappearance of the suppressive activity . Moreover, primed T lymphocytes treated with Dex in the presence of exogenous IL 2 enhanced the proliferative responses of fresh autologous PBMC stimulated by MPPS . Taken together, our data suggest that glucocorticoids inhibit the differentiation of T suppressor cells and that IL 2 is unable to reverse this inhibitory effect. Infect Immun, 1985 Feb, 47(2), 363 - 5 Candidacidal activity of myeloperoxidase: therapeutic influence of the enzyme in vivo; Wright CD et al.; Mice were injected intravenously with Candida albicans blastospores to establish chronic renal infection . Seventy-five percent of the animals inoculated with 10(6) blastospores died as a consequence of infection during the subsequent 60 days of observation . Intraperitoneal administration of 10 mU of partially purified human myeloperoxidase 1 day after injection of the pathogen increased survival of the mice from 25 to 80% over this time period . Administration of myeloperoxidase complexed with soluble C . albicans cell wall mannan abrogated the protective influence of the enzyme . These results demonstrate that exogenous myeloperoxidase has a therapeutic influence on murine renal candidiasis and suggest that exogenous myeloperoxidase may also be effective in the treatment of certain forms of candidiasis in humans . These results also demonstrate the important role of the mannan-binding function of myeloperoxidase for effective treatment of candidiasis and suggest a mechanism of inhibition of the candidacidal effect of free enzyme in vivo by mannan accumulating in tissue fluids. Dig Dis Sci, 1985 Feb, 30(2), 178 - 81 Candida albicans infection of gastric ulcer frequency and correlation with medical treatment . Results of a multicenter study; Di Febo G et al.; This paper reports the results of a multicenter prospective study of 188 consecutive patients affected by gastric ulcer, verified by endoscopy, in whom the frequency of a mycotic infection of the lesion was evaluated as well as the eventual influence of such pathology on the efficiency of medical treatment, the healing rate, and the healing time . A mycotic infection, defined as penetration of the periulcerous mucosa by the fungi, was found in only 13 patients (6.9%) . No significant differences were found in the healing rate and healing time among these patients treated with H2-receptor antagonists and a control group of 43 matched gastric ulcer patients treated in the same period with the same therapy . It would appear from the data that mycotic infections of the gastric ulcer do not modify the efficiency of medical treatment. N Z Med J, 1985 Jan 23, 98(771), 1 - 5 Pathogenic mechanisms in recurrent genital candidosis in women; Meech RJ et al.; A detailed analysis of the microbiological flora and investigation of the host immune response to Candida albicans was performed on 22 women presenting with a history of recurrent genital candidosis, as defined by at least four clinical episodes, with at least two episodes microbiologically proven, due to C albicans in the preceding 12 months . Disease due to C albicans could occur at low counts (10(2)-10(3)/ml) or very high counts (greater than 10(8)/ml) . Immunological investigations indicated that both hypersensitive and anergic states occur, the nature of the host response determining the clinical features noted on presentation . Polymicrobial mixed infections were also noted in six women . Recognition of the nature of the host response is important in understanding the pathogensis of recurrent candidosis and devising effective therapeutic regimes. Z Erkr Atmungsorgane, 1985, 165(3), 283 - 5 {Problem discussion of allergic reactions in patients with infection-induced bronchial asthma in Candida colonization outside the respiratory tract}; Manger R; Candida albicans colonization outside from the respiratory tract can occur as a side-effect of long lasting antibiotica therapy in patients with infection-induced asthma bronchiale and may induce in them allergic reactions . Based on own experiences the author reports on the frequency of Candida infections following antibiotica therapy and the effect of a therapy with Fungicidin on the number of dyspnoe attacks. Chemotherapy, 1985, 31(4), 318 - 23 Variation in microbial survival and growth in intravenous fluids; Rawal BD et al.; The survival and growth of aerobic and anaerobic bacteria, as well as a yeast, was studied in intravenous fluids over a 3-day period . Solutions were experimentally contaminated with pathogenic strains of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacteroides fragilis and Candida albicans . Samples of these solutions were tested on each day up to 3 days for determining viable numbers of the organisms by a membrane filtration method . Each organism showed a different survival/growth pattern in various infusion fluids . In 5% dextrose, C . albicans multiplied but only 2-3% of the initial viable cells of E . coli, P . aeruginosa, and S . aureus were detected after 3 days . In 0.9% sodium chloride, C . albicans and S . aureus showed growth and E . coli remained viable, but P . aeruginosa was not detected after 72 h . In lactated Ringer's solution, P . aeruginosa and C . albicans grew but E . coli and S . aureus were not detected after 72 h . In the amino acid solution, C . albicans, S . aureus and E . coli grew but P . aeruginosa and B . fragilis were not detected . Results indicate that the pattern of microbial survival and growth may be substantially different in various intravenous fluids. Am J Nephrol, 1985, 5(3), 169 - 75 Fungal peritonitis in patients on peritoneal dialysis: incidence, clinical features and prognosis; Johnson RJ et al.; Fungal peritonitis occurred in 17 patients on chronic peritoneal dialysis . The incidence of infection per 100 patient-dialysis months was 0.36 for patients on intermittent peritoneal dialysis and 1.6 for patients on continuous ambulatory dialysis (p less than 0.005) . Initial clinical findings included abdominal pain (76%), fever (59%), cloudy dialysate (76%) and poor dialysate outflow (6%) . 15 patients received antibiotics within 4 weeks of developing peritonitis . All infections were caused by yeasts, with Candida parapsilosis and Candida albicans as the most common species . 14 patients were unable to continue peritoneal dialysis due to persistent or relapsing infection or the development of complications . 2 of the 3 patients who were able to continue peritoneal dialysis were treated with catheter replacement, intraperitoneal miconazole and oral ketoconazole. Chemotherapy, 1985, 31(3), 211 - 5 Susceptibility of Candida spp . of clinical origin to lucknomycin, a new polyenic antibiotic; Sousa AS et al.; Lucknomycin is a new polyenic derivative antifungal agent obtained from a Streptomyces diastatochromogenes culture . The in vitro activity of the compound was tested against 403 strains of different Candida species of clinical origin by the Sabouraud Agar dilution method . The mean geometrical value of the minimal inhibitory concentrations (MIC) for Candida albicans was 0.85 microgram/ml, 6 times lower than the corresponding value of nystatin (5.29 micrograms/ml) and very close to that of amphotericin B (0.56 microgram/ml) . Lucknomycin was also 4-10 times more active than nystatin on other Candida species, with an MIC similar to those obtained with amphotericin B. Mycopathologia, 1985 Jan, 89(1), 59 - 63 Experimental candidiasis in iron overload; Abe F et al.; In an attempt to study the influence of iron overload on deep mycotic infection, experimental candidiasis was induced in mice . One group received intravenous injections of colloidal iron (60 mg/kg weight) for three consecutive days before intravenous inoculation of Candida albicans spores (1 X 10(7) . The other received the same number of Candida spores without iron overload . The animals in both groups were observed for 28 days . The Candida lesions, regardless of iron administration, were located mainly in the kidney . There was a marked difference in mortality between the two groups, i.e., 40% in the group without iron administration and 80% in the group with it . The higher mortality rate in the latter group may be explained by following reasons: increased serum iron and iron saturation (iron is essential to the growth of Candida), decreased phagocytic activity against intravenously inoculated Candida because of the saturation of the phagocytic cells by the preceding colloidal iron administration and enhanced proliferation of Candida, which tends to involve the kidney, exposed to abundant iron in the kidney due to increased excretion . The current experiment showed that excessive iron clearly promoted the proliferation of intravenously inoculated Candida in vivo. Folia Microbiol (Praha), 1985, 30(1), 34 - 41 Antimicrobial activity of methyl esters and nitriles of 2-cyano-3-(5'-R-2'-furyl)propenic acid; Balaz S et al.; Derivatives of 2-cyano-3-(2'-furyl)propenic acid with a markedly polarized double bond inhibit the growth of Chlorella pyrenoidosa, Saccharomyces cerevisiae, Candida albicans and Aspergillus niger at concentrations above 40 mumol/L . Their antibacterial activity (Escherichia coli B, Bacillus subtilis) is low . The biological effect increases with an increasing electron acceptor effect and decreasing hydrophobicity of the substituent on the furan ring . Substitution of methoxycarbony} group with cyano group in position 1 slightly increases the biological activity. J Antimicrob Chemother, 1985 Jan, 15(1), 69 - 75 New azole compounds: vibunazole (Bay n7133) and Bay L9139, compared with ketoconazole in the therapy of systemic candidosis and in pharmacokinetic studies, in mice; Lefler E et al.; Ketoconazole, a new imidazole: Bay L9139, and a new triazole: vibunazole (Bay n7133) were compared in therapy of systemic candidosis . CD-1 male mice were challenged with Candida albicans intravenously (greater than LD80), and treated twice a day, orally, for one month . The isolate of Can . albicans used, and isolates obtained after treatment with the antifungals, were susceptible to all three drugs (MICs less than or equal to 0.5 mg/l) . No drug was lethal to uninfected mice in doses of 200 mg/kg/day for one month . With therapy started on the day after infection, all three drugs at 50 or 100 mg/kg/day prolonged survival, compared with controls (P less than 0.05), with ketoconazole slightly superior to the other two drugs, but none did so at 25 mg/kg/day . At 200 mg/kg/day ketoconazole and vibunazole were protective, but L9139 was not, and this suggested synergistic toxicity of L9139 with Can . albicans infection, at this dose . With treatment begun on day 4, ketoconazole prolonged survival (P less than 0.005) at 200 or 100 mg/kg/day compared with controls, but ketoconazole at 10-50 mg/kg/day, and vibunazole and L9139 at 10-200 mg/kg/day were ineffective . Survivors had renal lesions and culture-proven residual infection . Pharmacokinetic studies indicated lower peak vibunazole and 9139 serum concentrations, and reduced area-under-curve (AUC), after 26 days of treatment, as against single dose administration . The relative inefficacy of vibunazole and L9139 appears to be related to unfavourable pharmacokinetic properties with continued administration. Int J Nucl Med Biol, 1985, 12(3), 243 - 7 {111In}oxine labelling of polymorphonuclear leucocytes: doubts concerning elution and effects on cell behaviour; Sheehan NJ et al.; Polymorphonuclear leucocytes (PMN) from normal human subjects were labelled with {111In}oxine (20 muCi 10(8) cells) . In the presence of 20% autologous serum (AS), dissociation of 111In from the cells resulted in mean losses of radioactivity of 13% at 3 h and 30% at 24 h . Adherence of 111In-labelled PMN to cultured porcine endothelial monolayers was increased by 40.7 +/- 31.6% after 60 min incubation in 20% AS at 37 degrees C when compared with unlabelled cells . Phagocytosis and intracellular killing of Candida albicans were unaltered by labelling . Elution of 111In from labelled PMN together with enhanced adhesiveness may have important implications for the study of PMN kinetics and the investigation of inflammatory disease. Dent J Malays, 1985 Jan, 8(1), 39 - 45 Oral candidiasis--its pleomorphic clinical manifestations, diagnosis and treatment; Ramanathan K et al.; Up to 60% of the population carry Candida albicans as part of the oral flora without having evidence of candidiasis . The pleomorphic clinical manifestations of oral candidiasis viz . thrush, denture stomatitis, angular cheilitis, median rhomboid glossitis, speckled leukoplakia, and chronic mucocutaneous candidiasis and its variants are briefly discussed . Current diagnostic techniques of oral candidiasis (OC) are reviewed . A simple and quick method of helping the clinician in the diagnosis of OC by taking a direct smear of the lesion is emphasized . OC is a 'disease of the diseased' . As a routine a full blood picture, serum iron and serum folate levels should be looked at . Several predisposing causes of OC need to be investigated . An up-date on the treatment of OC with nystatin, amphotericin B lozenges, clotrimazole and miconazole is made. Curr Genet, 1985, 9(2), 175 - 7 UV-induced instability in Candida albicans hybrids; Whelan WL et al.; Auxotrophic variants were obtained following UV-irradiation of Candida albicans hybrids which were heterozygous (+/+/-/-/) for various genetic markers (met, ade, his, lys) . Some variants contained less DNA (per cell) than did the hybrids from which they originated; such variants were considered to arise in a process which resulted in generalized reduction in ploidy . These results provide the basis for a cyclic parasexual system (2n X 2n----4n----2n) for genetic analysis in this amictic diploid species. Drugs Exp Clin Res, 1985, 11(11), 745 - 6 Do quinolones really augment the antifungal effect of amphotericin B in vitro? Overbeek BP, Rozenberg-Arska M, Verhoef J. The minimum inhibitory concentrations (MICs) for amphotericin B and the quinolones norfloxacin and ciprofloxacin against 30 clinical isolates of Candida albicans were determined in various liquid media . Interaction studies were carried out to investigate a possible synergistic action of the quinolones on the antifungal effect of amphotericin B . No interaction between the drugs studied was observed in any of the media used. Magnesium, 1985, 4(5-6), 339 - 44 Normocalcemic tetany and candidiasis; Galland L; We have observed a high frequency of chronic Candida albicans infection and of allergic sensitization to candida among patients with normocalcemic latent tetany (LT) . Among 50 LT patients, 34% suffered from recurrent or chronic candida infection by history, 24% showed evidence of active infection and 48% demonstrated type I hypersensitivity to C . albicans extract on intradermal testing . Treatment with oral antifungal drugs and allergy desensitization to Candida produced complete relief of symptoms in 44% of the patients, with remission occurring for symptoms of depression, irritable bowel syndrome, fatigue, premenstrual tension, headache, anxiety and back pain . The complex relationship between candidiasis and Mg deficit is discussed . Patients with LT, refractory symptoms and a history of prolonged antibiotic exposure or recurrent candida infection should be considered for oral antifungal therapy and candida desensitization. Folia Microbiol (Praha), 1985, 30(6), 493 - 500 Differences in amino acid transport and phospholipid contents during the cell cycle of Candida albicans; Dudani AK et al.; Drugs like L-ethionine, 1,10-phenanthroline and 3-(2-thienyl)-DL-alanine which arrest Saccharomyces cerevisiae cells in the G1 phase, were unable to arrest Candida albicans cells . However, C . albicans could be arrested in G1 after a prolonged stationary phase . As compared to normal cells, there was a selective reduction in the level of accumulation of valine and glutamate in G1-arrested cells, while the phospholipid polar head group ratio was not significantly altered . When G1-arrested C . albicans cells were again allowed to grow, the level of different phospholipids started increasing at about the time of bud emergence (2.5 h) whereas reduced levels of accumulated valine and glutamate recovered within 1 h . The recovery of phospholipids and amino acid transport are two distinct events during the progression of C . albicans cells from G1 to S phase. Arch Immunol Ther Exp (Warsz), 1985, 33(2), 339 - 44 Antifungal properties of 1,2-dihydro-3-methylpyrido-(3,2-e)-as-triazine dihydrochloride (I-476); Wieczorek J et al.; Antifungal activity of compound I-476 (1,2-dihydro-3-methylpyrido{3,2-e}as-triazine dihydrochloride) was evaluated in vitro and in vivo . Minimal concentration inhibiting the growth of pathogenetic and saprophytic fungi in vitro ranged from 3.1 to 25 micrograms/ml . The in vivo experiments were performed in a model of experimental candidiasis in Balb/c mice . Antifungal activity of I-476 was measured by the survival time of the animals and the number of living Candida albicans cells in the kidney and spleen of the animals infected and then treated with the compound in question . A single intraperitoneal dose of I-476 markedly prolonged the survival time of mice with experimental candidiasis . The compound administered for 5 subsequent days, diminished the number of Candida albicans cells in the kidney and spleen or caused their complete elimination from these organs. Rev Mal Respir, 1985, 2(3), 161 - 6 {Yield of the thoracoscopic biopsy in experimental pulmonary infections in the immunosuppressed rabbit}; Viallat JR et al.; Using thoracoscopy lung biopsy we investigated the bacteriological diagnostic yield in immunodepressed and/or infected NZ rabbits . 84 rabbits were used: 18 controls, 30 immunodepressed rabbits and 36 rabbits immunodepressed and then infected with Aspergillus fumigatus . Candida albicans or B.C.G . The thoracoscopy technique was the one we designed for humans, the instruments were adapted to the size of animals . Thoracoscopy biopsy results were compared to those of surgical biopsies made in the same animals . The results of both techniques were similar: indeed, the sensitivity of thoracoscopy biopsy was 88.9% in immunodepressed rabbits (versus 100% with surgical biopsies), 86% in the group of rabbits infected with B.C.G . (versus 86%), 90.1% in rabbits infected with Aspergillus fumigatus (versus 100%) and 88.9% in rabbits infected with Candida albicans (versus 100%) . The indications for thoracoscopic lung biopsy in immunodepressed patients with infectious lung diseases are drawn from these experimental data, from our experience and the known mortality and morbidity of surgical lung biopsy. Crit Rev Microbiol, 1985, 12(3), 223 - 70 Antigenic variability of Candida albicans; Poulain D et al.; The concepts of modern biology lead us to think that all structures are liable to continual changes . Ultrastructural and biochemical methods have been able to objectify such a dynamic in Candida albicans, an opportunistic yeast . A broad analysis of antigens is a reliable way to study the antigenic variations which concern this organism . Numerous information on somatic and metabolic antigens of C . albicans is available at the moment . Paradoxically, if one accepts studies dealing with dimorphism, very few works have shown antigenic variability of this species or investigated the mechanisms involved in such a variability . The few approaches done in this way tend to prove that it may be possible to link together the expression of particular antigens and the behavior of the yeast, particularly when it acts as a pathogen. Chemotherapy, 1985, 31(5), 395 - 404 Correlation of susceptibility test results in vitro with response in vivo: ketoconazole therapy in a systemic candidiasis model; Polak A et al.; In a previous study with flucytosine (5-FC) susceptibility of 40 Candida albicans isolates in vitro proved statistically correlated with response in systemic murine candidiasis in vivo, although exceptions occurred with individual isolates . For the present analogous study with ketoconazole, 58 C . albicans isolates were used of which 38 were from the 5-FC study and 20 were added to equalize the numbers of serotype A (n = 30) and B (n = 28) and to make the range of susceptibility in vitro to ketoconazole continuous and wide . The widest range of ketoconazole susceptibility was noted for the minimal inhibitory concentrations on Kimmig and Casitone agars (0.015-256 micrograms/ml) and disk zone diameters on YNB agar (0-54 mm), whereas with disk tests on other media, the range of 50% inhibitory concentrations, relative inhibition factors and MICs on serum agar remained narrow and/or showed strong ties . The Spearman's rank correlation between the in vitro activities determined with the various parameters showed wide variation consistent with p values from less than 0.001 to greater than 0.05 . The serotype B isolates generally were more susceptible than the A isolates (p less than 0.02 for the majority of parameters) . Evaluation of response in vivo was hampered by the low activity of ketoconazole on the murine infection with any of the isolates, the range of the ED50's being only 10- greater than 100 mg/kg . The serotype B infections exhibited significantly better response (p less than 0.05) than the serotype A infections . The overall correlation (Spearman's rank) of the susceptibility test results in vitro with the response in vivo was poor (p less than 0.05 for almost all parameters) suggesting very limited if any precise predictive values of the susceptibility tests in vitro with ketoconazole against C . albicans . However, the narrow range of the ED50 suggests relatively little variation in the response of the different isolates in vivo and similarly small variation was also noted in some of the tests in vitro. Mol Gen Genet, 1985, 200(3), 500 - 2 Isolation of genes from Candida albicans by complementation in Saccharomyces cerevisiae; Rosenbluh A et al.; A genomic library of the asexual pathogenic yeast Candida albicans was constructed in the S . cerevisiae vector YEp13 . The library contains a representation of the entire genome with a probability of 99% . The expression of the genes of C . albicans in S . cerevisiae was examined and two mutations his3-1 and trp1-289 of S . cerevisiae were complemented by the cloned genes of C . albicans . The hybridization data indicates that the plasmids complementing the mutations of S . cerevisiae contain sequences from C . albicans. Mol Gen Genet, 1985, 200(1), 162 - 8 Heat shock induces chromosome loss in the yeast Candida albicans; Hilton C et al.; The heat shock protocol described in this paper causes mitotic instability in log phase Candida albicans cells . Such instability is induced in diploid, aneuploid and tetraploid strains . The strains analysed are multiple heterozygotes which facilitates the detection of mitotic instability as manifested by the formation of homozygotes . Strains previously shown to be carrying cis linked mutant alleles show coincident segregation of the linked alleles . Conversely, strains which carry unlinked mutant alleles display no such coincident segregation . This segregation of complete linkage groups suggests that heat shock is inducing chromosome loss in C . albicans . The application of this protocol to the genetics of the imperfect fungus C . albicans has produced evidence of at least three chromosomes. Crit Rev Microbiol, 1985, 12(1), 45 - 93 Morphogenesis in Candida albicans; Odds FC; This review will survey environmental controls on the morphology of Candida albicans, describe the cellular and ultrastructural events associated with morphological transitions in this fungus, and attempt to relate biochemical phenomena that have been reported to be associated with dimorphic change to C . albicans cell biology . The synthesis of the cell wall of C . albicans and its control remain largely undiscovered, but it is clear that the cell wall is the principal component involved in shape determination . Possible models for C . albicans dimorphism will be critically reviewed. Thymus, 1985, 7(2), 69 - 84 Modulation of polymorphonucleate-mediated cytotoxicity against Candida albicans by thymosin alpha 1; Bistoni F et al.; In the present work we analyze the effects of thymosin alpha 1 treatment on the number and the candidacidal activity of murine polymorphonuclear leukocytes . The data we obtained showed that the treatment with thymosin alpha 1 (100 micrograms/Kg s.c.) 10, 8, 6, 4 and 2 days before the assay may result in a significant numerical augmentation of circulating polymorphonucleates in the peripheral blood, as well as of their candidacidal activity when measured in vitro in both a 4-h cytotoxicity assay and a CFU inhibition assay against Candida albicans microorganisms . On the other hand, a single dose of thymosin alpha 1 (500 micrograms/Kg s.c.) 3 days before the assay resulted in a significant decrease of the candidacidal activity of mouse polymorphonucleates . The data are discussed with regard to the immunomodulating capacity of thymosin alpha 1 and to our previously reported observations concerning the ability of the drug to modulate the resistance against systemic Candida albicans infection. Microbios, 1985, 42(168), 103 - 9 Incorporation of dexamethasone by Candida albicans; Ghannoum MA et al.; The incorporation of 3H-dexamethasone into Candida albicans has been studied . The results indicate that the steroid is incorporated unchanged and primarily into the cell wall and membrane of the organism . The incorporation appears to be of a noncovalent type. Microbiologica, 1985 Jan, 8(1), 85 - 99 N-acetyl-D-glucosamine-induced morphogenesis in Candida albicans; Cassone A et al.; N-acetylglucosamine is a morphogenic effector in the human pathogenic yeast Candida albicans . Depending on temperature, N-acetylglucosamine induces yeast-mycelial conversion or chlamydospore formation . N-acetylglucosamine is also a carbon source for growth in the yeast form . Germ-tube formation, i.e . the intermediary of yeast-mycelial conversion, is induced at temperatures in excess of 33 degrees C; at lower temperatures the yeast or the pseudomycelial form of the organism predominates . 2-Deoxyglucose, at concentrations which do not affect yeast growth, is a potent inhibitor of N-acetylglucosamine-induced germ-tube formation . N-acetylglucosamine suffices as both the inducer and the carbon sources for morphogenesis and both transcription and translation are required for the yeast to mycelial transition . The metabolism of N-acetylglucosamine is essentially the same for yeast phase cells (28 degrees C) and germ-tube forming cells (37 degrees C): enzymes for N-acetylglucosamine uptake and catabolism are equally well induced by gene expression at 28 degrees C and 37 degrees C . During germ-tube formation, the chitin content and the activity of the regulatory enzyme chitin synthase increase . Germ-tube formation in C . albicans can also be induced gratuitously by a number of N-acetylhexosamine derivatives (N-acetylglucosamine covalently linked to agarose, N-acetylmannosamine, hyaluronic acid, colloidal chitin, and mucin) . These compounds are not taken up by the yeast cells and do not support growth which suggests that germ-tube formation is triggered by a cell-surface receptor mechanism . It is proposed that, after binding to the receptor, N-acetylglucosamine produces an intracellular message which primes the cell for morphogenesis . This message would ultimately be responsible for the choice of the mode of growth, spherical versus apical, that is characteristic of yeast or mycelial form. Diagn Microbiol Infect Dis, 1985 Jan, 3(1), 1 - 5 Proteolytic activity of Candida albicans and other yeasts; Schreiber B et al.; Clinical isolates of C . albicans (75 strains) and other yeasts (20 strains) were evaluated for their ability to produce a carboxyl acid proteinase in an effort to assess its potential role as a virulence factor . Yeasts were categorized as to the infectious process present in the patient: (1) isolates from patients with invasive disease, (2) isolates from patients with possible invasive disease, (3) isolates from superficially infected patients and (4) isolates from noninfected, colonized patients . Yeasts were grown for 7 days in medium containing bovine serum albumin (BSA) as the sole nitrogen source . The amount of extracellular proteinase was measured at pH 3.2, using BSA as substrate . The majority (97%) of C . albicans isolates produced a detectable proteinase . Some non-C . albicans isolates produced proteinase; however, the amount of activity was generally less than for C . albicans . No correlation was found between the amount of proteolytic activity and the degree of invasiveness of the strains. Arch Dermatol, 1985 Jan, 121(1), 119 - 24 Fungus-host relationship in candidiasis . A brief review; Montes LF et al.; Candidiasis and its causative agent, Candida albicans, have been under continuous study in our clinics and laboratories for the past 20 years . Cultured cells of C albicans and tissues from natural and experimental infections were used for observations by light microscopy, transmission electron microscopy, scanning electron microscopy and freeze fracture techniques . In cultures, the cells of C albicans revealed a more complex cell wall, plasma membrane, intracellular organelles, and biochemical organization than those described in classic text-books on mycology . In infected tissues, noteworthy characteristics of C albicans were prominent vacuoles and invasion of host cells with subsequent intracellular localization and lysis of tissues surrounding the fungus . These findings are discussed in relation to their importance in the pathogenesis and management of candidiasis and to the mechanism of action of anticandida agents. Child Abuse Negl, 1985, 9(1), 27 - 9 Vaginitis due to Gardnerella vaginalis and to Candida albicans in sexual abuse; De Jong AR; Sexually transmitted diseases may be transferred to children and adolescents during voluntary or involuntary sexual contact . Two children are reported with the unusual association of sexual abuse and Candida albicans or Gardnerella vaginalis infections . Awareness of the techniques for diagnosis of these infections is essential for appropriate management of the abused child . These organisms should not be considered normal flora when found in symptomatic children and adolescents and should raise the possibility of sexual abuse. Boll Ist Sieroter Milan, 1985, 64(2), 126 - 30 Suppressor T cells role in the unresponsiveness to Candida albicans in chronic mucocutaneous candidiasis; Barnaba V et al.; We investigated the immune function of two members of the same family, mother and son, affected by chronic mucocutaneous candidiasis (CMC) . In these cases CMC was not associated with hypofunction of endocrine organs, while the son showed histological feature of chronic active hepatitis . We observed a decrease in OKT4/OKT8 ratio and an increased suppressor cell function in both patients . Elimination of cytotoxic/suppressor T cells by lysis of these cells with OKT8 plus complement markedly improved lymphocyte proliferative responses to Candida antigens but not to unrelated antigens . These data suggest that specific suppression is probably responsible for failure of Candida albicans clearance in CMC patients. Acta Microbiol Hung, 1985, 32(4), 305 - 13 Lipid content and ESR determination of plasma membrane order parameter in Candida albicans sterol mutants; Pesti M et al.; Sterol intermediates of ergosterol biosynthesis in seven sterol mutants of Candida albicans were determined by gas-liquid chromatography . Only one of them could synthetize ergosterol, while in the others sterol biosynthesis was blocked beyond zymosterol . Alterations in sterol composition were correlated with a slight increase in saturation and a decrease in the chain length of fatty acids, and increases in phosphatidylinositol and phosphatidic acid, and decreases in phosphatidylcholine and phosphatidylserine contents . During exponential growth, as measured on their protoplasts using the intercalated fatty acid spin probe, 5-doxylstearic acid, these single mutants exhibited higher plasma membrane order parameters than their ergosterol-producing parental strain, designated 33 erg+, as follows: erg-12 greater than erg-16 greater than erg-37 much greater than erg-2 greater than erg-20 greater than erg-40 greater than erg-41 greater than 33 erg+ . The mutants displayed significantly higher phase-transition temperatures, measured in a reconstituted lipid-water dispersion, than their parental strain. Microbiol Immunol, 1985, 29(7), 609 - 23 Effect of aculeacin A, a wall-active antibiotic, on synthesis of the yeast cell wall; Yamaguchi H et al.; A wall-active, amphophilic antibiotic aculeacin A significantly but incompletely inhibited in vitro the activity of beta-(1,3)glucan synthase prepared from highly susceptible yeasts Saccharomyces cerevisiae and Candida albicans . In contrast, comparable cell-free preparations from S . cerevisiae active in chitin synthase or mannan synthase were insensitive to the antibiotic, suggesting selectivity of its action in synthesis of the yeast cell wall . An electron microscopic study of the effects of aculeacin A at 0.31 micrograms/ml, the optimally active concentration, on osmotically stabilized C . albicans cells revealed morphological alterations in both cell walls and cell membranes . Deformation in contour and derangement of the layered structure of the cell wall were prominent . In addition, massive fibrous material of beta-glucan-like microfibrils was occasionally extruded from the cell surface . Accompanying this effect on the cytology of the cell wall, ultrastructural and functional impairment of the cell membrane was demonstrated by transmission and freeze-fracture electron microscopic techniques . These data suggest that aculeacin A affects synthesis of the yeast cell wall through not only selective blockage of beta-(1,3)glucan synthase, as a result of a primary interaction with the cell membrane, but also inhibition of the fabrication of beta-glucan or other wall components into well-organized cell walls. Int Arch Allergy Appl Immunol, 1985, 78(3), 243 - 8 Direct interaction of guinea pig eosinophils and adrenergic agents; Masuyama K et al.; The effects of alpha- and beta-adrenergic stimulation on guinea pig eosinophil functions were studied . Both enhanced glucose uptake of eosinophils at a concentration of 5 X 10(-5) M after a 24-hour incubation . Decreased eosinophil chemotaxis and dose-dependent inhibition of arylsulfatase release from eosinophils induced by opsonized Candida albicans were observed when eosinophils were incubated with beta-adrenergic agents, but not with alpha-adrenergic agents . On the other hand, alpha stimulation inhibited phagocytosis of opsonized C . albicans by eosinophils and NBT reduction at concentrations of 8 X 10(-5) and 5 X 10(-5) M, respectively, but beta stimulation at the same concentrations did not . This suggests that the regulatory effect of adrenergic agents on phagocytosis in eosinophils is different from that in macrophages and polymorphonuclear leukocytes. Acta Microbiol Pol, 1985, 34(1), 55 - 8 Adherence of Candida to mucosal epithelial cells; Macura AB; Adherence abilities of 45 Candida strains to human buccal and vaginal epithelial cells in vitro were tested in two media: 0.9% saline and phosphate buffer . Candida albicans cells adhered more strongly to epithelial cells than fungal cells of other Candida species . These findings were statistically significant according to Mann-Whitney's "U" test with buccal epothelial cells in both of the test media and with vaginal cells in saline only. Acta Derm Venereol, 1985, 65(6), 515 - 20 Persistent generalized lymphadenopathy: immunological and mycological investigations; Torssander J et al.; Immunological and mycological investigations were carried out in 21 Swedish homosexual males . One of them had AIDS, one pre-AIDS and 19 lymphadenopathy of whom 18 fulfilled the criteria of persistent generalized lymphadenopathy (PGL) as defined by the Centers for Disease Control, Atlanta, (CDC) . The patients were investigated immunologically with respect to their in vitro lymphocyte reactivity to various mitogens . The patients with AIDS and pre-AIDS belonged to the group of 8 patients with low response to mitogens . Blood helper T cell percentages and serum beta 2-microglobulin concentrations correlated with the PHA reactivity . Three patients, with the diagnoses AIDS, pre-AIDS and PGL respectively, had clinical signs of oral candidiasis with rich growth of Candida albicans in culture . These were all low responders to mitogen stimulation . Six cases of tinea pedis were diagnosed and seemed to be distributed among the patients irrespectively of the severity of their immunological disorders. Acta Derm Venereol, 1985, 65(5), 424 - 7 Candida albicans infections in leg ulcers and surrounding skin after the use of ointment impregnated stockings; Hansson C et al.; Six elderly women treated with double elastic bandages for chronic venous leg ulcers presented a clinical picture beneath these bandages as seen in intertriginous candidiasis . Painful, bright red, glistening skin lesions with pustules, denuded skin and scales were seen . Cultures on Sabouraud's agar from skin erosions and toe webs confirmed the suspicion of Candida albicans infection . Treatment with topically applied clotrimazole cream resulted in relief of pain and healing of skin lesions . There is a possibility of the Candida albicans having been transmitted from the toe webs by the bandages, and that the bandages creates a microenvironment suitable for growth of the yeast. Acta Derm Venereol, 1985, 65(4), 355 - 8 Candidiasis: the isomorphic response; Witkowski JA et al.; Two uncontrolled insulin dependent diabetic patients had Candida albicans infection with the unique manifestation of erythematous scaling papulopustules at the sites of excoriation . In one patient, the clinical presentation suggested herpes zoster . Recognition of this picture and the contributing factors, i.e . Candida infected finger nails and elevated blood sugar will permit early use of appropriate antifungal therapy. Acta Derm Venereol, 1985, 65(2), 106 - 10 The functions of polymorphonuclear leukocytes emigrating into the skin; Csato M et al.; The functions of polymorphonuclear leukocytes (PMNs) emigrating into the skin and of others separated simultaneously from the circulation were determined and compared in healthy individuals . The PMNs emigrating into the skin were separated with a skin chamber technique . The C3 rosette forming capacities of the skin migrating and the circulating PMNs were similar . The chemotactic responsiveness was evaluated using three different chemoattractants: zymosan-activated serum, casein and lymphocyte-derived chemotactic factor . The skin PMNs gave practically no chemotactic response in the Boyden chamber, irrespective of the chemoattractant used . On the other hand, the skin PMNs exhibited higher plastic surface adherence, nitroblue tetrazolium reduction and Candida albicans killing activities . The data indicate that some functional activities of PMNs undergo alteration during in vivo emigration into the skin . The alterations, overall, may be of importance in the physiological protective function of the skin. Lancet, 1984 Dec 22, 2(8417-18), 1415 - 8 Immunoblot analysis of the serological response in systemic candidosis; Matthews RC et al.; To investigate the heterogeneity in antibody response to the various antigenic determinants of Candida albicans in patients with disseminated candidosis 201 serial serum samples from 45 patients with proven systemic candidosis were examined by immunoblotting (Western blotting) for antibodies to C albicans type A NCTC 3153 . 40 patients had detectable antibody . 26 different antigen bands, ranging from 104 kD to 23 kD, were identified . Despite wide variation in the antigens recognised by different patients, the antibody responses fell into six patterns (A to F) . 13 patients infected during an outbreak of systemic candidosis gave the same response (A) . Of a further 7 patients with this response, 2 had isolates indistinguishable from the outbreak strain . Group B responses were associated with leukaemias and lymphomas . Groups C-F responses were seen in 9 patients . Production of antibody to a 47 kD antigen, common to all six groups, occurred in all those who recovered from the infection and may therefore be of prognostic significance . Whether this antigen could be used as the basis of a vaccine remains to be determined. Cancer Res, 1984 Dec, 44(12 Pt 1), 5594 - 8 Comparison of in vitro and in vivo differentiation of myeloblastic leukemia of the RFM/Un mouse; Weinberg JB et al.; Various human and mouse myeloid leukemia cell lines can differentiate to mature myeloid or monocytoid cells in response to different agents . The myeloblastic leukemia of the RFM/Un mouse (the RF.AML line) was studied here to determine its ability to differentiate after in vitro and in vivo treatment . The RF.AML cells were passed in vivo by i.v . or i.p . injection of freshly harvested leukemic spleen cells or in vitro-passaged leukemia cells . The cells proliferated in the spleen and peritoneal cavity . The RF.AML cells had the appearance of myeloblasts or myelomonoblasts on Wright's stain, had slight positivity for peroxidase, and lacked staining for nonspecific esterase . The cells grew in suspension in vitro with a doubling time of 48 hr . Various phorbol diester tumor promotors inhibited proliferation and incorporation of thymidine into the RF.AML cells . Phorbol myristate acetate (10 to 100 nM) caused the cells to adhere to plastic, and enhanced the phagocytic ability of the cells for Candida albicans . The RF.AML cells had specific receptors for phorbol dibutyrate, binding 0.37 +/- 0.03 (S.E.) pmol of {3H}phorbol dibutyrate/10(6) cells after a 2-hr incubation at 4 degrees with 50 nM {3H}phorbol dibutyrate . Thirty-three to 300 nM dexamethasone caused 19 to 37% of the cells to become nonspecific esterase positive and enhanced their phagocytosis of C . albicans . Likewise, 0.5 or 1.0 microM 13-cis-retinoic acid, or 0.6 or 1.2% dimethyl sulfoxide enhanced the phagocytic ability of the RF.AML cells but had no effect on the adherence, proliferation, or nonspecific esterase activity . None of the treatments induced lysozyme activity in the cells or rendered the RF.AML cells able to produce H2O2 in response to phorbol myristate acetate treatment in vitro . In vivo treatment of mice with RF.AML present with phorbol myristate acetate or dexamethasone did not induce differentiation of the RF.AML cells or alter the survival of the animals . Thus, although the RF.AML cells differentiate in vitro in response to various agents, in vivo differentiation was not seen in this model. Clin Otolaryngol, 1984 Dec, 9(6), 351 - 4 Clinical and bacteriological studies in otitis externa in Dar es Salaam, Tanzania; Manni JJ et al.; The symptoms and signs as well as the bacterial flora from the auditory canals of 54 Tanzanian patients (74 ears) living in Dar es Salaam and suffering from otitis externa were studied . Itching and pain were the most common symptoms and erythema and secretion were the prevalent clinical findings . Pseudomonas aeruginosa was found in 38%, Aspergillus in 24%, Staphylococcus aureus in 18% and Candida albicans in 14% . Bacterial cultures from the auditory canals of 21 healthy subjects revealed only normal skin flora. Bangladesh Med Res Counc Bull, 1984 Dec, 10(2), 65 - 70 General yeast infection in Bangladeshi women using contraceptives; Rahman KM et al.; A study on the vaginitis due to candida infection among Bengali women using different contraceptives was carried out . A total of 368 patients using three different contraceptives (Pills, Injectables, IUD) and 316 age and parity matched women as control were studied . The incidence of vaginal yeast infection was highest (17.6%) among pill user . In control group, the incidence is lower (6.7%) . The difference is statistically significant (P less than 0.05) . No significant difference in vaginal yeast infection in women using other two types of contraceptives (Injection, IUD) in contrast to control group was found (P greater than 0.5) . Candida albicans was the most common type of yeast infection (91.8%) . No Torulopsis glabrata was isolated in this study . we did not find any relationship between duration of contraceptive usages and higher incidence of vaginal candidiasis (P greater than 0.5) . This study also indicated that culture examination is much more sensitive than microscopic examination of vaginal swab in detecting yeast infection. Int J Pediatr Nephrol, 1984 Dec, 5(4), 223 - 6 Renal candidiasis in infancy--a case with fungus ball obstruction; Prat O et al.; A sixteen day old infant developed candiduria after surgery on a single functioning, hydronephrotic kidney with ureteropelvic junction stenosis . Masses of candida albicans caused obstruction of the ureter with acute anuria . Endoscopic relief of the obstruction together with aggressive antifungal therapy led to irradication of the fungal infection . This case history emphasizes the fact that candida infection in early childhood should be evaluated carefully . Unfortunately no guidelines are yet available for the indications and the preferred mode of treatment, and length of therapy of infantile renal candidiasis. J Gen Microbiol, 1984 Dec, 130 ( Pt 12), 3303 - 11 The action of 2-deoxy-D-glucose on the incorporation of glucose into (1----3)-beta-glucan in stationary phase cultures of Candida albicans; Gale EF et al.; 2-Deoxy-D-glucose added to cultures of Candida albicans in the stationary phase of growth inhibited the incorporation of glucose into the (1----3)-beta-glucan fraction of the organisms . In the presence of ATP and cell extracts it was converted to 2-deoxy-D-glucose phosphate and when UTP was also present, material with the electrophoretic properties of UDP-2-deoxy-D-glucose was formed . In similar conditions glucose formed glucose phosphates, UDP-glucose and other products . Evidence was obtained that the analogue, after conversion to a phosphate derivative, was an inhibitor of phosphoglucomutase . When C . albicans was grown in the presence of 2-deoxy-D-glucose for 24 h, analogue residues became incorporated into the (1----3)-beta-glucan fraction and the subsequent rate of incorporation of glucose into that fraction was enhanced . The rate of turnover of glucose in this beta-glucan fraction was greater than in controls . Pretreatment of cultures with beta-glucanase, or incubation under conditions known to stimulate endogenous beta-glucanases, increased the subsequent rate of glucose incorporation and this increase was enhanced by growth in the presence of 2-deoxy-D-glucose . The analogue thus had the effect of altering the stability and glucose-acceptor function of (1----3)-beta-glucan chains . This could affect the properties of the polymer network leading to the known effect of the analogue in delaying the onset of phenotypic resistance to amphotericin methyl ester in stationary phase cultures of C . albicans. Chemioterapia, 1984 Dec, 3(6), 354 - 7 In vitro effect of some antibiotics on phagocytic index of human neutrophils; el-Hawary A et al.; The effect of the following antibiotics, in serum concentration equivalent to that of the usual therapeutic level, on the in vitro phagocytosis of killed Candida albicans by normal human neutrophils was studied: gentamicin, tobramycin, netilmicin, amikacin, aztreonam, cephradine, cefamandole, ticarcillin, spectinomycin, amoxycillin, clavulanic acid and Augmentin . Each antibiotic was tested 10 times . Results showed slight inhibition of phagocytosis by all antibiotics except amoxycillin. Biochem Int, 1984 Dec, 9(6), 735 - 44 Induction of N-acetyl-D-glucosamine catabolic enzymes and germinative response in Candida albicans; Natarajan K et al.; The regulation of N-acetylglucosamine catabolic enzymes was studied in both yeast and germ tube forms of the dimorphic fungus Candida albicans . The induction pattern of these enzymes was the same for yeast cells incubated at 28 degrees C and in cells incubated at 37 degrees C which formed germ tubes . However, the level of activity of these enzymes in germ tube stage is lower as compared to yeast phase cells . A strain of C . albicans that did not form germ tubes was endowed with a pronounced ability for induction of N-acetylglucosamine catabolic enzymes . This result suggests that germ tube formation and N-acetylglucosamine metabolism are mutually exclusive events. J Reprod Med, 1984 Dec, 29(12), 863 - 8 Influence of estrogen and normal flora on vaginal candidiasis in the rat; Larsen B et al.; The vaginal epithelium of randomly bred albino rats normally does not contain yeast . This study demonstrated that estrogen-primed, castrated rats could be colonized by Candida albicans following intravaginal challenge, whereas rats not treated with estrogen remained resistant to colonization . The bacteriologic conditions of the vagina were also studied in yeast-colonized and non-yeast-colonized rats . No evidence of bacterial interference with yeast colonization was obtained from this study since the vaginal flora of the estrogen-treated, yeast-colonized rats was more abundant and diverse than that of the non-estrogen-treated rats, which were resistant to yeast colonization . Scanning electron microscopy of the vaginal epithelium of yeast-colonized rats showed that C . albicans entered the mycelial phase during colonization of the vagina . It also appeared that the mycelia penetrate the cornified vaginal epithelial cells. J Gen Microbiol, 1984 Dec, 130 ( Pt 12), 3295 - 301 Analysis of wall glucans from yeast, hyphal and germ-tube forming cells of Candida albicans; Gopal PK et al.; Acid-soluble and alkali-insoluble glucan fractions were prepared from yeast, hyphal and germ-tube forming cells of Candida albicans . Alkali-insoluble glucan was also extracted from purified yeast cell walls . Paper chromatography of partial acid hydrolysates confirmed that the glucan preparations contained beta(1----3)- and beta(1----6)-chains but no mixed intra-chain beta(1----3)/(1----6) linkages . Methylation and 13C-NMR analyses showed that the acid-soluble glucan consisted of a highly branched polymer composed mainly (67.0% to 76.6%) of beta(1----6)-linked glucose residues . The alkali-insoluble glucan from yeast and hyphal cells contained from 29.6% to 38.9% beta(1----3) and 43.3% to 53.2% beta(1----6) linkages . Alkali-insoluble glucan from germ-tube forming cells consisted of 67.0% beta(1----3) and 14% beta(1----6) linkages . Branch points accounted for 6.7%, 12.3% and 17.4% of the residues in the alkali-insoluble glucan of yeast, germ-tube forming and hyphal cells, respectively. J Gen Microbiol, 1984 Dec, 130 ( Pt 12), 3285 - 93 Protein synthesis and amino acid pool during yeast-mycelial transition induced by N-acetyl-D-glucosamine in Candida albicans; Torosantucci A et al.; Protein synthesis at different stages of yeast-mycelial transition induced by N-acetyl-D-glucosamine in Candida albicans was evaluated by following incorporation of radioactive amino acids into the acid-insoluble cellular material . In passing from the early germ-tube formation (60-90 min) to the mature hyphal cell (240-270 min) there was a marked decrease in the capacity for protein synthesis . Apparently, this decrease was not due to a decreased amino acid uptake into the soluble cellular pool or to exhaustion of carbon/energy source in the inducing medium with consequent arrest of growth . Protein synthesis, however, did not decay when amino acids at high concentration were added to the medium fostering the yeast-mycelial transition and this effect was potentiated by glucose . Analysis of the intracellular amino acid pool showed that both germ-tubes and hyphal cells were relatively depleted of several amino acids as compared to the yeast-form cells, whereas in the hyphae there was a higher concentration of glutamic acid/glutamine, the latter being the predominant component . These modulations in amino acid pool composition were not seen when yeasts were converted to hyphae in an amino acid-rich induction medium . This study emphasizes that yeast-form cells of C . albicans may efficiently convert to the mycelial form even under a progressively lowered rate of protein synthesis, and suggests that initiation of hyphal morphogenesis in the presence of N-acetyl-D-glucosamine is somehow separated from cellular growth. Clin Exp Immunol, 1984 Dec, 58(3), 581 - 6 Candida albicans polysaccharide extract (MPPS) and PPD stimulate the production of interleukin-1 and lymphocyte proliferation; Lombardi G et al.; Peripheral blood mononuclear cells (PBMC) were stimulated in vitro either with Candida albicans polysaccharide extract (MPPS) or with PPD . Both MPPS and PPD driven lymphocyte proliferation was strictly dependent on the presence of macrophages . In fact purified T cells failed to proliferate unless adherent cells were added . The ability of monocytes to produce interleukin-1 (IL-1) was then investigated . Both MPPS and PPD caused the release IL-1 into the culture supernatant, as measured in a direct thymocyte proliferative assay . MPPS and PPD also stimulated the production of IL-1 by the mouse macrophage like line P388D1 . These data support the view that the antigen specific activation of human T cells by MPPS and PPD requires both antigen presentation and IL-1 production. J Bacteriol, 1984 Dec, 160(3), 884 - 8 Sensitivity to nikkomycin Z in Candida albicans: role of peptide permeases; Yadan JC et al.; The uptake of tritiated nikkomycin Z, a potent inhibitor of chitin synthetase, is mediated by a peptide transport system in Candida albicans . Kinetic transport assays with radioactive di- and tripeptides and competition studies suggest that two distinct systems operate in this yeast . Nikkomycin Z was transported through one of these systems, common to di- and tripeptides . A peptide transport-deficient mutant was isolated on the basis of its resistance to nikkomycin Z . The mutant lost most of its capacity to take up dipeptides but simultaneously increased its ability to transport tripeptides . These results indicate that C . albicans handles peptides through multiple transport systems and adjusts their expression to environmental conditions. Infect Immun, 1984 Dec, 46(3), 831 - 4 Inhibition by sugars of Candida albicans adherence to human buccal mucosal cells and corneocytes in vitro; Collins-Lech C et al.; The adherence and inhibition of adherence of Candida albicans to epithelial cells was studied for human cells obtained from skin (corneocytes) and buccal mucosa . The yeast adhered to both kinds of cells, although in somewhat greater numbers to buccal mucosal cells . Adherence to the cells of different individuals was variable, but the ratios of values for the two kinds of cells from a single subject were quite constant . Inhibition of adherence was produced by several sugars, including the aminosugars mannosamine, glucosamine, and galactosamine . The pattern of inhibition produced by the sugars was similar for the two types of cells . Pretreatment of the yeast with mannosamine, followed by dilution to a subinhibitory concentration, produced some inhibition of yeast-buccal mucosal cell attachment, indicating some direct interaction between the sugar and the fungal cell . These data suggest that the mechanisms whereby C . albicans attaches to corneocytes and to buccal mucosal cells are probably similar. Clin Immunol Immunopathol, 1984 Dec, 33(3), 371 - 80 Immunodeficient CBA/N mice respond effectively to Candida albicans; Carrow EW et al.; An immune defect in CBA/N mice diminishes their ability to respond adequately to certain well-defined antigens . Since the contribution of T and B cells to immunity in candidiasis has not been clearly defined, it was hoped that CBA/N mice might prove a useful model for the study of specific responses to Candida albicans . Therefore, immunodeficient CBA/N and immunocompetent CBA/J mice were immunized by two cutaneous inoculations of viable C . albicans B311 given 2 weeks apart and challenged iv 14 days after the second inoculation . Delayed-type hypersensitivity (DTH) was tested with a membrane-derived antigen (B-HEX) 7 days following the second inoculation, and lymphocyte stimulation with B-HEX, a cytoplasmic antigen (SCS), and mitogens was done at 12 days . Antibody to SCS was determined by ELISA 2 days after DTH testing and 28 days after iv challenge, at which time the animals were sacrificed for quantitative culture of kidneys and brains . Naive CBA/N mice were no more susceptible to challenge than CBA/J mice in that the mean log colony-forming units (CFU) were 3.79 and 5.48, respectively . Both strains responded to immunization by a similar reduction in CFU, a marked DTH response (e.g., reactions at 24 hr were 1.12 mm for CBA/N and 1.34 mm for CBA/J), and significant and similar quantities of antibody . The immune defect in CBA/N mice had no demonstrable effect on the development of immune responses to infection with C . albicans. J Antibiot (Tokyo), 1984 Dec, 37(12), 1719 - 26 Cefodizime, an aminothiazolyl cephalosporin . IV . Influence on the immune system; Limbert M et al.; Studies concerning the activity of cefodizime (HR 221), on certain aspects of the immune response, were conducted . It was found that lymphocytes from Balb/c mice treated with 3 and 30 mg/kg/day of cefodizime display increased responsiveness to B-cell mitogens and specific antigens . Also, the amount of antigen specific antibody producing plaque forming cells was increased in these mice and was accompanied by a rise in the specific IgG haemagglutinin titer . These effects were not observed in lymphocytes obtained from NMRI mice that had been treated with cefodizime . Peritoneal macrophages from NMRI mice, treated with cefodizime prior to harvesting of the cells, contained increased levels of lysosomal enzymes, developed enhanced chemiluminescent reaction to stimuli and showed elevated pinocytosis rates . Furthermore, NMRI mice treated with cefodizime during the immunization, developed enhanced DTH-reaction, when challenged with the antigen (SRBC) . The prophylactic treatment of Balb/c mice with cefodizime (2 X 30 mg/kg/day ip for 4 days) significantly prolonged the mean survival time of the animals after intravenous infection with Candida albicans 200/175 (16.7 days as against 3.5 days in the case of the controls) . This stimulatory effect of cefodizime on the host defence system was not observed for NMRI mice . Treatment with latamoxef or cefoperazone under the same experimental conditions did not reduce the susceptibility of mice to C . albicans . The protective activity of cefodizime against C . albicans in Balb/c mice, may be due to the immuno-stimulatory activity of this agent. J Am Vet Med Assoc, 1984 Dec 1, 185(11), 1328 - 30 Candidiasis in captive pinnipeds; Dunn JL et al.; Diagnosis, treatment, and possible pathogenesis of candidiasis were studied in 5 species of pinnipeds in captivity: gray seal (Halichoerus grypus), harbor seal (Phoca vitulina), northern fur seal (Callorhinus ursinus), California sea lion (Zalophus californianus), and northern elephant seal (Mirounga angustirostris) . The animals were kept outdoors in a freshwater exhibit . Candidiasis was characterized by purulent nasal discharge, inflammation of the lips at the mucocutaneous junction, periocular alopecia, vaginitis, and dermatitis . Administration of ketoconazole at dosages of 5 mg/kg BID and 10 mg/kg SID controlled the disease . Wild gulls were suspected as vectors of Candida albicans. Lancet, 1984 Nov 24, 2(8413), 1174 - 5 Clinical evaluation of a recombinant hepatitis B vaccine; Jilg W et al.; Recombinant hepatitis B vaccine prepared from antigen expressed in yeast was given to 30 healthy young volunteers . Seroconversion rates and anti-HBs levels were compared with those in a control group matched for age and sex who had received plasma-derived hepatitis B vaccine . 4 weeks after the third immunisation results were similar in the two groups . In the recombinant vaccine group the immune response developed more slowly during the early phase and seroconversion rates and mean anti-HBs levels were slightly lower in males; this probably reflects use of a lower dose of recombinant vaccine (10 micrograms compared with 20 micrograms of the plasma vaccine) . Side-effects were slight and antibody titres against Candida albicans were not increased in recipients of the recombinant vaccine. J Antibiot (Tokyo), 1984 Nov, 37(11), 1279 - 83 Chryscandin, a novel peptidyl nucleoside antibiotic . I . Taxonomy, fermentation, isolation and characterization; Yamashita M et al.; A novel antifungal antibiotic, chryscandin was found in the culture broth of a strain of fungi . The producing organism was subsequently identified as Chrysosporium pannorum . The antibiotic obtained as colorless needle crystals (C20H23N7O6, MW 457) is active against Candida albicans and Gram-positive bacteria, but it is ineffective against filamentous fungi and Gram-negative bacteria . Acute toxicity is very low in mice. Biochem J, 1984 Nov 1, 223(3), 707 - 14 Purification and properties of a beta-1,6-glucanase from Penicillium brefeldianum; Schep GP et al.; An inducible endo-beta-1,6-glucanase was purified from Penicillium brefeldianum by DEAE-cellulose, Bio-Gel P-150 and high-pressure liquid chromatography . The final preparation was essentially free from beta-1,3-glucanase and beta-glucosidase activities . Sodium dodecyl sulphate/polyacrylamide-gel electrophoresis revealed one protein band with an Mr of 44000 . The Vmax . and Km values were calculated to be 624 units (mumol/min)/mg and 2.78 mg/ml respectively . The glucanase had lytic activity against mycelial cells of the yeast Candida albicans . The yield of purified beta-1,6-glucanase from 100 mg dry weight of freeze-dried culture filtrate varied from 60 to 180 units. Br J Ophthalmol, 1984 Nov, 68(11), 841 - 5 Exogenous ocular candidiasis associated with intravenous heroin abuse; Sorrell TC et al.; Seven young men developed disseminated candidiasis within 10 days of a single episode of intravenous heroin abuse . Sequential development of eye and skin lesions was noted in all cases . The bone or costal cartilage was involved in five . Ocular manifestations of candidiasis included episcleritis, chorioretinitis, and endophthalmitis . A presumptive diagnosis of candida chorioretinitis was established rapidly by culture of Candida albicans from involved skin and costal cartilage . Systemic therapy with amphotericin B plus 5-fluorocytosine resulted in cure of the episcleritis, chorioretinitis, osteomyelitis, costochondritis, and skin infection . Pars plana vitrectomy with local instillation of amphotericin B was required to cure chorioretinitis associated with vitreal extension of infection. Antibiotiki, 1984 Nov, 29(11), 869 - 72 {Sensitivity of Candida strains to polyenic antibiotics in the treatment of oral candidiasis}; Boiko GI et al.; Sensitivity of 146 clinical strains of Candida albicans to nystatin, levorin and amphoglucamine was studied on solid media with the replica method . The strains were isolated from 79 patients with candidiasis of the oral mucosa . It was found that sensitivity of the fungi to the polyenic antibiotics was different which should be considered in treatment of candidiasis . On the basis of the mean MICs for the clinical strains and their distribution by the MICs it was shown that the activity level of levorin and amphoglucamine was higher than that of nystatin . During the treatment resistance of the Candida strains to the polyenic antibiotics increased and cross resistance developed which required application of other treatment means. Appl Environ Microbiol, 1984 Nov, 48(5), 1051 - 2 Ethanol contamination in commercial buffers: ethanol contaminating tris-maleate and other commercial buffers induces germ tube formation in Candida albicans; Pollack JH et al.; Evidence is presented for the presence of trace amounts of ethanol in certain commercial buffers . It was shown that germ tube formation occurring in Candida albicans suspended in the buffers was due to the contaminating ethanol. J Med Chem, 1984 Nov, 27(11), 1447 - 51 A novel peptide delivery system involving peptidase activated prodrugs as antimicrobial agents . Synthesis and biological activity of peptidyl derivatives of 5-fluorouracil; Kingsbury WD et al.; As an approach to the development of antimicrobial agents, a novel peptide carrier system was designed, based on the chemical instability of alpha-substituted glycine analogues, with the explicit intent of actively transporting therapeutically useful compounds into microbial cells . Peptides containing 5-fluorouracil (5-FU) linked to the peptide backbone were selected to test the feasibility of this new delivery system . These peptide conjugates were designed such that they would be substrates for both the microbial peptide permeases and peptidases . After entry into cells, enzymatic hydrolysis of the peptide generates an unstable alpha-(5-FU)-glycine that spontaneously decomposes to release 5-FU . The 5-FU-peptide conjugates were tested for antifungal (Candida albicans) and antibacterial (Escherichia coli) activity and were found to have antimicrobial activities comparable to free 5-FU . Noninhibitory peptides antagonized the antimicrobial activities of the 5-FU-peptide conjugates but not of free 5-FU, a result consistent with peptide transport mediated entry of the peptide conjugates into cells . Further support for this conclusion was provided by the finding that biological activities were dependent upon peptide stereochemistry. Clin Immunol Immunopathol, 1984 Nov, 33(2), 199 - 209 A purified polysaccharide isolated from Candida albicans induces antibody response in vitro by human peripheral blood lymphocytes and discriminates between sera from normal and Candida albicans-infected individuals; Wirz M et al.; A purified polysaccharide extracted from Candida albicans (MPPS), stimulates in vitro synthesis of specific antibodies by human peripheral blood lymphocytes . These antibodies can be detected by a sensitive enzyme-linked immunoassay . The same assay can be applied to the quantitation of anti-candida antibodies in serum . Statistically significant differences were found between sera of normal and candida-infected individuals. Biull Eksp Biol Med, 1984 Nov, 98(11), 601 - 2 {Nature of the cells regulating the production of a migration inhibition factor in C57BL/6 strain mice with low response to Candida albicans antigen}; Vorob'ev KV et al.; The authors studied cell regulation of macrophage migration inhibition factor (MIF) in response to Candida albicans antigen in C57BL/6 mice . It was revealed that low MIF production in response to this antigen is determined by the existence of specific suppressors which are inhibited by cyclophosphamide . The differences between the mouse lines are accounted for by different activity of suppressor cells of the thymic origin, which is confirmed by the treatment with anti-Thy1-serum and by bone marrow cell transfer. Antimicrob Agents Chemother, 1984 Nov, 26(5), 699 - 701 Fungicidal activity of tioconazole in relation to growth phase of Candida albicans and Candida parapsilosis; Beggs WH; It was shown that tioconazole possesses an important property not shared by ketoconazole and miconazole, its well-known relatives in the imidazole group of antifungal drugs . At a concentration of 3.8 X 10(-5) M, tioconazole, like miconazole, caused rapid 2- to 3-log reductions in CFU per milliliter when added to late-logarithmic-phase Candida albicans or Candida parapsilosis cells . Only tioconazole, however, exerted similar reductions when added to diluted stationary-phase cultures . This growth-phase-independent lethal action has important clinical implications and may explain the superior performance of tioconazole, which was observed in earlier comparative drug studies. J Dent Res, 1984 Nov, 63(11), 1306 - 9 Humoral immune responses to adenoviruses, herpes virus type 1, and Candida albicans in sera of dental patients with oral neoplastic and periodontal diseases; Winters WD et al.; Levels of immunoglobulin class-specific antibodies as determined by solid phase radioimmunoassays to herpes simplex virus type 1 (HSV-1), human adenovirus types 5, 21, and 31 and to Candida albicans in sera from untreated healthy dental patients were not significantly different from levels of these antibodies in sera from untreated dental patients with benign oral tumors, oral carcinoma, or periodontal disease . These results show that higher levels of immunoglobulin class-specific antibodies to HSV-1, the three adenoviruses, or Candida albicans are not a consistent finding in sera from patients with oral cancer when comparisons are made with healthy patients and patients with other oral diseases. Mycopathologia, 1984 Oct 30, 88(1), 61 - 3 Suppression of humoral response during the course of Candida albicans infection in mice; Valdez JC et al.; This paper aims at demonstrating the non-specific immunosuppression as regards thyme-dependent antigens sheep erythrocytes (SRBC) during the course of Candida albicans systemic infection . Three lots of syngeneic/BALB/c mice, 8-12 weeks of age, were used . The first normal lot was inoculated via the intraperitoneal route with a (SRBC) suspension (4 X 10(8) cells ml) in a Hank's balanced saline solution . The primary response of antibodies formed by splenic cells was measured from 4 to 8 days after inoculation using the direct plaque forming cells technique . The second lot was infected by the same route with a suspension of Candida albicans (1 X 10(7) cells) . Positive retrocultures from the blood and kidneys of these infected mice were obtained . These yeasts cultivated in a Sabouraud medium were harvested after 20 h at 37 degrees C . Following the same methodology the immune response to SRBC was determined . The serum obtained from infected mice was transferred to a third lot of mice at different intervals during the course of the infection . The immune response to SRBC was done by the direct plaque-forming cells technique . Controls were carried out using normal donors and recipients . A suppression of the immune response was obtained as from the 2nd day of inoculation up to the 28th day . It was not possible to transfer such suppression passively by means of the serum . These results suggest that the systemic infection by Candida albicans induce a non-specific immunosuppression in the organism, already demonstrated in viral infections, bacteria, protozoaria and metazoaria in mammals . In some way, this will contribute to explain the mechanisms of immune response to Candida albicans. Am J Med, 1984 Oct 19, 77(4C), 37 - 41 Influence of ceftriaxone on natural defense systems; Gialdroni Grassi G et al.; The in vitro and in vivo effects of ceftriaxone, a newly developed cephalosporin, on phagocytes and T-cell subsets were studied . Ceftriaxone in vitro did not interfere with phagocytosis, phagocytosis-dependent metabolic activation, and microbicidal activity (against Staphylococcus aureus and Candida albicans) of human neutrophils at doses ranging from 10 to 320 micrograms/ml . In vitro chemotaxis was markedly inhibited both in the presence of and after 30 minutes of exposure to 40 micrograms/ml of ceftriaxone . Six normal adult volunteers were given 2 g of antibiotic intravenously every 24 hours for six days . The in vivo effects of ceftriaxone on neutrophil functions and T-cell subsets were investigated before and 30 minutes after injection on the first and third days . No change in any phagocyte function (chemotaxis, phagocytosis, phagocytosis-dependent metabolic activation, and microbicidal activity) or in the distribution of T-cell subpopulations was observed. J Leukoc Biol, 1984 Oct, 36(4), 549 - 50 Functions of neutrophils in endemic Chediak-Higashi syndrome; Goihman-Yahr M et al.; Endemic Chediak-Higashi Syndrome occurs in a restricted geographic area (Pregonero, State of Tachira, Venezuela) . Neutrophils from these patients were unable to digest Candida albicans in vitro, but showed normal or increased metabolic activities . This finding supports the view that the endemic syndrome is bona fide Chediak-Higashi Syndrome. Hum Pathol, 1984 Oct, 15(10), 996 - 8 Massive thrombosis as a result of triple infestation of the pulmonary arterial circulation by Ascaris, Candida, and Mucor; Stermer E et al.; A 35-year-old man with a brief history of dyspnea and fever experienced rapid progressive respiratory distress and died shortly after being hospitalized . Postmortem examination revealed thrombotic occlusion of the pulmonary tree; the thrombotic material showed Ascaris lumbricoides, Candida albicans, and Mucor . This rare coincidence is an unexpected complication of ascariasis that has not been described previously. Int J Oral Surg, 1984 Oct, 13(5), 411 - 5 Tobacco smoking and denture wearing as local aetiological factors in median rhomboid glossitis; Arendorf TM et al.; The importance of tobacco smoking and denture wearing in the aetiology of median rhomboid glossitis (MRG) has been evaluated in 39 patients . Significantly more of the MRG patients (85%) smoked tobacco compared with the corresponding proportion (41%) of the 39 healthy age-and sex-matched control subjects . Their tobacco consumption was also heavier . A significantly greater proportion of the MRG patients wore their dentures continuously compared with the controls . The number of MRG patients who were both tobacco smokers and denture wearers was significantly increased above that of the control group, as was the number who both smoked and wore dentures continuously . Only 1 patient neither smoked nor wore dentures and she was taking an antidepressant (imipramine hydrochloride) with a reported association with oral candidosis . It is suggested that these local factors may play a part in the development of MRG by favouring the local proliferation of Candida albicans on the dorsum of the tongue . Although conservative or surgical treatment may provide relief, management should also include attention to possible predisposing local factors. Chemioterapia, 1984 Oct, 3(5), 310 - 5 Fungal infections in hematological neoplastic disease: the possibility of chemoprophylaxis; Fanci R et al.; Immunoelectrosmophoresis (IEOP) was used to detect antigens of Candida albicans in the sera of 90 patients with hemolymphoblastosis . A higher percentage of sensitive results occurred in patients with acute myeloid leukemia; moreover, most of the serologically positive patients showed severe leukopenia and neutropenia (WBC less than 1000/microliter; neutrophils less than 200/microliter) . According to the results of IEOP assays, a prophylactic treatment with standard dosages of amphotericin B or myconazole was instituted in positive cases . Treatment schedules were randomized in order to assess the effect of each drug . The therapy resulted in serological negativity in 60% of the patients treated with amphotericin B and 57% of those who were given myconazole. Ann Gastroenterol Hepatol (Paris), 1984 Oct-Nov, 20(5), 275 - 80 {Contribution of proctosigmoidoscopy in colonopathies caused by Candida albicans}; Bensaude RJ; When the endoscopic lesion typical anorectocolonic candidiasis is absent, the author demonstrates that mild cases of colonopathy due to Candida albicans do not always present the commonly described classic symptoms of anomarginal, copperhued, running lesions.. . The proctosigmoidoscope reveals that in half of the cases with concurrent ordinary digestive troubles and Candida albicans present in the stools, the mucosa is congestive and, very often, the rectal cytology disturbed . A good correlation exists between modifications of the rectosigmoid mucosa and the number of Candida albicans colonies isolated from the feces of these patients . In addition, anal pruritus, a rare clinical event by itself, can be attributed to candidiasis using the proctosigmoidoscope and coproculture . Mild anorectocolonic candidiasis can exist as a secondary infection with chronic inflammatory colitis (ulcerative colitis, etc.) or acute mucous colitis . These infections can also be primary and, in these cases, sometimes appear consequent to recent antibiotic therapy. Arch Microbiol, 1984 Oct, 139(2-3), 221 - 4 Cytochemical and ultrastructural studies of Candida albicans . III . Evidence for modifications of the cell wall coat during adherence to human buccal epithelial cells; Tronchin G et al.; Ultrastructural modifications of the cell wall coat of Candida albicans during adherence to host cells were investigated using various cytochemical techniques . Attachment of the fungus to buccal epithelial cells appeared to involve spatial rearrangement of their cell wall surface . In particular adhering yeast developed a fibrogranular surface layer visualized by the periodic acid--thiocarbohydrazide--silver proteinate technique (a polysaccharide detection technique); Concanavalin A binding sites detected on their cell wall coat were highly increased . Attachment of yeasts to epithelial cells appeared mediated by fibrillar structures or polysaccharidic granules distributed on the cell wall coat . But free extra-cell wall material containing mannoproteins released from the yeast surface suggested additional mechanisms. Antimicrob Agents Chemother, 1984 Oct, 26(4), 570 - 4 Decreased activity of UMP pyrophosphorylase associated with resistance to 5-fluorocytosine in Candida albicans; Whelan WL et al.; UMP pyrophosphorylase activity was assayed in crude lysates prepared from Candida albicans . Specific activity of UMP pyrophosphorylase was high in clinical isolates which were susceptible to 5-fluorocytosine . Resistant clinical isolates displayed low activity, and partially resistant (heterozygous) isolates displayed intermediate activity . Segregation from the heterozygous state resulted in a homozygous susceptible segregant with high UMP pyrophosphorylase activity and a homozygous resistant segregant with low activity . The observed specific activities were consistent with the hypothesis that specific activity was determined by the sum of the activities due to the dominant (FCY) and recessive (fcy) alleles of the resistance gene . Strains which possessed little UMP pyrophosphorylase activity released uracil into the medium when grown in the absence of 5-fluorocytosine; this result suggested that recycling of intracellular uracil is a normal function of this enzyme. Z Kinderchir, 1984 Oct, 39(5), 305 - 9 {Importance of infection following laparotomy in childhood}; Grussner R et al.; Laparotomy was performed on 579 children at the University Clinic of Paediatric Surgery in Mainz from 1.1.1975 to 31.12.1982 . The children were up to 15 years of age; appendicitis or inguinal and umbilical hernia cases were not included . Postoperative sepsis occurred in 74 patients (12.8% of all children with laparotomy); in 51 cases positive bacteriological findings were seen besides the clinical and clinicochemical ones . Sepsis morbidity was particularly high in children who had not yet completed their first year of life (postoperative sepsis occurring in approximately every fourth infant); among the disease patterns, the following were particularly prominent: Defects of the abdominal wall (23 out of 50 children developed postoperative sepsis); intestinal atresia (18 out of 59 children); intestinal perforation (11 out of 39 children) . In addition, sepsis morbidity was enhanced after relaparotomies . Gram-negative bacteria were most frequent among the 51 patients with bacteriologically positive findings; these bacteria consisted mostly of representatives of the group of enterogenous pathogens . These groups of bacteria were also the most frequently occurring pathogens in mixed and secondary infections . 33 out of 74 children with postoperative sepsis died . The mortality rate was 68% in prematurely born infants compared with mature newborns . Lethality was highest among children with congenital defects of the abdominal wall and intestinal perforations . Among the patients with bacteriologically positive findings the lethality was particularly high with multiple attacks of sepsis, in case of septitides caused by multiple pathogens, by Candida albicans and after relaparotomy. J Med Microbiol, 1984 Oct, 18(2), 249 - 54 Susceptibility of fungi in mouthrinse specimens from patients with haematological malignancies; Kostiala AA et al.; Fungi isolated from mouthrinse specimens during episodes of acute pseudomembranous fungal stomatitis and deep-seated mycoses in patients with haematological malignancies were tested for susceptibility to seven antifungal agents . Topical treatment of stomatitis with clotrimazole or chlorhexidine did not induce any change in the susceptibility of oral Candida albicans . Treatment of deeper mycoses with 5-fluorocytosine, however, resulted in a significant increase in oral strains resistant to this agent . Of C . albicans strains isolated, 7% were resistant to 5-fluorocytosine greater than 32 micrograms/ml . One patient died of disseminated mycosis during treatment with this drug; the resistant C . albicans was isolated from the mouth, liver, spleen and kidneys . Strains of Torulopsis glabrata and C . krusei resistant to 5-fluorocytosine were also found in some patients . Organisms resistant to 5-fluorocytosine were generally sensitive to polyenes and imidazoles. J Leukoc Biol, 1984 Oct, 36(4), 505 - 20 Immunological activation of polymorphonuclear neutrophils for fungal killing: studies with murine cells and blastomyces dermatitidis in vitro; Brummer E et al.; The interaction of elicited murine polymorphonuclear neutrophils (PMN) and the thermally dimorphic fungal pathogen Blastomyces dermatitidis in vitro was studied . The PMN elicited intraperitoneally with thioglycollate, in normal mice or mice immune to B dermatitidis, failed to reduce colony forming units (CFU) of B dermatitidis in the inoculum in a 4-hr in vitro assay, even in the presence of 10% fresh immune serum . In contrast, PMN elicited intraperitoneally in immune mice by injection of nonviable B dermatitidis cells significantly reduced inoculum CFU (60 +/- 5%) under the same conditions . Furthermore, nonviable B dermatitidis intraperitoneally (i.p.) in normal mice or nonviable Candida albicans i.p . in immune mice failed to elicit peritoneal exudate cells that reduced inoculum CFU in this system . These results support the concept that PMN, elicited in a site by means of an immunological reaction, acquired enhanced microbicidal activity . The fungicidal activity of immunologically elicited PMN was shown to be most effective at high effector to target cell ratios (1,000:1), maximal within 2 hr of coculture, and significantly enhanced in the presence of fresh immune serum compared to heat-inactivated immune serum, normal mouse serum, or fetal bovine serum . Such PMN also had significantly enhanced fungicidal activity against C albicans compared to normal PMN . Fungicidal activity was abrogated in the presence of catalase, implicating hydrogen peroxide generation as the killing mechanism in the activated cells. Infect Immun, 1984 Oct, 46(1), 13 - 21 Effects of zinc on stationary-phase phenotype and macromolecular synthesis accompanying outgrowth of Candida albicans; Anderson JM et al.; When cultures of Candida albicans which had entered stationary phase due to the depletion of zinc (zinc-limiting conditions) were compared with cultures which had entered stationary phase due to the depletion of another growth-limiting component (zinc-excess conditions), at least two cellular characteristics were found to differ: (i) zinc-limited cells appeared more homogeneous and larger on the average than zinc-excess cells, and (ii) zinc-limited cells evaginated on the average of 40 min later than zinc-excess cells . In the present study, it is demonstrated that the distribution of volumes for a stationary-phase culture of zinc-excess cells is skewed towards very small volumes, but even the smallest cells contain nuclei; in contrast, the volumes of zinc-limited cells are evenly distributed around a much larger mean value; the evagination kinetics of zinc-excess cells released into fresh medium are far less synchronous than are those of zinc-limited cells, and the smaller cells in the population take much longer to evaginate than do the larger cells; the onset of net RNA accumulation and achievement of a maximum rate of {3H}uridine incorporation occur significantly earlier in zinc-excess cells than in zinc-limited cells released into fresh medium; and the onset of net protein accumulation and {3H}leucine incorporation occur significantly earlier in zinc-excess cells than in zinc-limited cells released into fresh medium . These results indicate that although zinc-excess cells are extremely heterogeneous in volume, they may still be homogeneously blocked in the nuclear division cycle, and that the later average evagination time of released zinc-limited cells may be due to a delay in the onset of protein synthesis, which in turn may be due to the time necessary to reaccumulate zinc to levels sufficient for the reinitiation of RNA synthesis. J Invest Dermatol, 1984 Oct, 83(4), 286 - 9 Enriched epidermal Langerhans cells are potent antigen-presenting cells for T cells; Bjercke S et al.; Human epidermis was separated from dermis by means of a suction blister device and dissociated with trypsin . The epidermal cell (Ec) suspensions contained 2-6% Langerhans cells (Lc) . Using a new rosette technique for enrichment of Lc, suspensions were obtained that contained 50-92% viable Lc . Ec, enriched Lc, or peripheral blood monocytes (Mo) were cocultured with or without antigens (Candida albicans, herpes simplex virus) and autologous T lymphocytes from sensitized donors . Strong proliferative T-cell responses were obtained provided Ec, enriched Lc, or Mo were also present . Furthermore, Lc were more effective than similar numbers of Mo in inducing T-cell responses to the antigens tested, and Lc did not require the presence of significant numbers of keratinocytes to exert this function. Mycopathologia, 1984 Sep 30, 87(3), 167 - 70 Detection of antibodies against Candida albicans ribosomes by the enzyme linked immunosorbent assay; Levy R et al.; Enzyme linked immunosorbent assay was found to be a convenient method for the investigation of antibodies in mice immunized with Candida albicans ribosomes . Antibodies against the ribosomal antigen were detected in all the sera of mice (ICR and BALB/c) immunized with ribosomes and incomplete Freund's adjuvant and in some of the sera of mice immunized with ribosomes only; the titer of antibodies varied from 1:320 to 1:10 240 . Vaccination of mice with ribosomal protein and IFA resulted in a high titer of antiribosomal antibodies . Treatment of ribosomes with pronase abrogated the capacity of the ribosomes to elicit anti ribosomal humoral responses, suggesting that the antibodies detected were directed against the protein moiety of the ribosomes . The presence of antibodies in sera of immunized mice could not be correlated with the protection afforded by the ribosomal vaccination. Mycopathologia, 1984 Sep 30, 87(3), 135 - 40 Antifungal drug susceptibility testing . A critical review; Stevens DA; The advent of new antifungal drugs provides clinicians with therapeutic options, and it is anticipated requests for fungal susceptibility testing in vitro will increase . Our own laboratory's experience indicates that results can be provided promptly even to distant medical centers . The need in this setting is standardization of procedures, so correlations with in vivo outcome can be made with in vitro results . The variables affecting current testing methods are reviewed . Newer methods of testing are summarized, including our experiences using a spectrophotometer as a tool to assay inhibition . Our understanding of the mechanisms underlying the results with this and classical methods are presented . Several methods were applied to a population survey of Candida albicans isolates, using the drug flucytosine as an example . The results were correlated with in vivo outcome in a mouse model of systemic candidosis . The in vitro results, in general, predicted survival, but exceptions occurred, and it appears the in vitro results provide a relative but not absolute indication of outcome. Eur J Biochem, 1984 Sep 3, 143(2), 273 - 6 Mode of action of miconazole on yeasts: inhibition of the mitochondrial ATPase; Portillo F et al.; Miconazole {( 1-{2-(2,4 dichlorophenyl)-2-(2,4 dichlorophenyl)methoxy}ethyl}-1 H-imidazole) completely inhibited growth of Saccharomyces cerevisiae and Candida albicans on glycerol at 10 microM . 50 microM was needed to achieve the same effect during growth on glucose . Miconazole inhibited competitively the mitochondrial ATPase of S . cerevisiae with a Ki of 1 microM . F1 activity of the enzyme was not affected . Mutants resistant to miconazole were isolated . The ATPase of these mutants was resistant to 10 microM miconazole . Higher concentrations of miconazole inhibited the ATPase of the plasma membrane . The inhibition of the S . cerevisiae enzyme was competitive with a Ki of 50 microM . The results point to the mitochondrial ATPase as the primary target of miconazole action at least during growth on non-fermentable carbon sources. J Oral Rehabil, 1984 Sep, 11(5), 419 - 27 Visco-elastic properties of four currently used tissue conditioners; De Mot B et al.; About 60% of complete denture wearers experience a mostly painless inflammation of the palatal mucosal membrane . Especially prosthetic trauma and Candida albicans infection are assumed as aetiological factors . The treatment can be prosthetic or medicamentous, dependent on the cause . In this connection tissue conditioners could be very effective by their visco-elastic properties . Four tissue conditioners have been examined (Coe Comfort, FITT, Ivoseal, Visco Gel) for their impression softness and elastic recovery . All tests have been done on 20 mm specimens . The length of the specimens was measured during a 10 min compression and a 60 min relaxation . Eight ageing times have been taken into consideration . From the results large differences appear between the various tissue conditioners . Two main groups can be distinguished . FITT and Ivoseal are harder materials, whereas Coe Comfort and Visco Gel are softer . The ageing time has a clear hardening influence especially on Visco Gel . Visco Gel appears to be the best tissue conditioner by its relative plasticity during the first hours and its elastic behaviour during a longer ageing period . The clinical relevance of these materials is certainly not proved by this study . Further research will show this. Trop Geogr Med, 1984 Sep, 36(3), 293 - 5 Bacteriologic studies in external otitis in Dar es Salaam, Tanzania; Manni JJ et al.; The bacterial flora from the auditory canals of 54 patients (74 ears) with external otitis was studied . Pseudomonas aeruginosa was found in 38% . Aspergillus in 24%, Staphylococcus aureus in 18% and Candida albicans in 14% . Bacterial cultures from the auditory canals of 21 healthy subjects produced only the normal skin flora. Cell Immunol, 1984 Sep, 87(2), 546 - 52 Resistance and susceptibility to infection in inbred murine strains . IV . Effects of dietary zinc; Salvin SB et al.; Mice of several inbred strains have been fed diets containing either large amounts of zinc (300 ppm Zn), small amounts of zinc (5 ppm Zn), or routine laboratory mouse chow . When the mice are fed on a high-zinc diet, murine strains, such as C3H/HeJ, AKR/J, and CBA/CaJ, which are normally susceptible to infection with Candida albicans and which normally release low titers of migration-inhibition factor (MIF) in vivo into the circulation, become more resistant to infection with C . albicans and release higher titers of MIF in vivo into the circulation . In addition, their capacity to elicit delayed type hypersensitivity responses may be enhanced . When the mice are maintained on a low-zinc diet, murine strains, such as C57Bl/10SNJ, which are normally resistant to infection with C . albicans and which normally release high titers of MIF in vivo into the circulation on appropriate antigenic challenge, become more susceptible to infection and release lower titers of MIF into the circulation . Under these conditions of low-zinc concentrations in the diet, their capacity to elicit delayed type hypersensitivity may be reduced . Thus, the concentration of zinc in the diet may have a pronounced effect on some in vivo parameters of cell-mediated immunity. Ann Immunol (Paris), 1984 Sep-Oct, 135D(2), 145 - 59 Antibody levels to Candida albicans carbohydrate and major cytoplasmic antigens isolated from standard and patient strains; Karwowska W et al.; A solid phase radioimmunoassay (RIA) and ELISA were used to detect human antibodies to Candida albicans (CA) organisms or purified fractions, namely, carbohydrate-rich fraction (CRF) and cytoplasmic peptides (SSF) of CA . IgG antibodies to either whole organisms or to CRF were found in sera obtained from patients with chronic mucocutaneous candidiasis (CMCC) or digestive candidiasis, as well as in healthy control sera . In patient sera, no correlation between the clinical stage of disease and the IgG anti-CRF levels was found . In contrast, antibodies to SSF were absent in healthy control sera . IgM anti-SSF in the absence of IgG anti-SSF were found in sera of patients with recent digestive candidiasis, and low levels of IgM and IgG Ab were detected in sera of CMCC patients . The lack of correlation between IgG anti-CRF levels and clinical status can, in part, be explained by the individual variability of Candida strains and by the inadequacy of the laboratory standard antigens in the antibody assays used . The clinical relevance of different tests to detect anti-CA antibodies is discussed. Antimicrob Agents Chemother, 1984 Sep, 26(3), 364 - 7 Analysis of pH and buffer effects on flucytosine activity in broth dilution susceptibility testing of Candida albicans in two synthetic media; Calhoun DL et al.; We examined the influences of different pH levels and three different buffers on flucytosine activity against 12 isolates of Candida albicans in two synthetic media, yeast nitrogen base (YNB) and synthetic amino acid medium-fungal (SAAMF), using broth dilution techniques and measuring the endpoints of visual MICs and turbidimetric 50% inhibitory concentrations . The two media were originally prepared as follows: YNB, unbuffered, pH 5.6; SAAMF, buffered with morpholinepropanesulfonic acid-Tris, pH 7.4; the resultant geometric mean MIC and 50% inhibitory concentration of 5-FC were 78- and 32-fold higher, respectively, in SAAMF . Raising the pH of YNB or lowering the pH of SAAMF had virtually no effect on these differences in MIC and 50% inhibitory concentration in the two media . In contrast, virtually all of the discrepancy appeared to be due to morpholinepropanesulfonic acid-Tris, which exerted concentration-dependent inhibition of flucytosine activity not evident when N-2-hydroxyethylpiperazine-N'-ethanesulfonic acid or phosphate buffer systems were substituted . In other turbidimetric studies, growth was slowed more than 50% in YNB as the pH was raised to 7.4, regardless of which buffer was used . Based on our studies, we recommend modifying the composition of SAAMF by substituting a nonantagonistic buffer if any buffer is to be used with SAAMF in the testing of flucytosine . With this modification, SAAMF warrants further study as a generally applicable medium for fungal-susceptibility testing. J Gen Microbiol, 1984 Sep, 130 ( Pt 9), 2219 - 28 A comparison of volume growth during bud and mycelium formation in Candida albicans: a single cell analysis; Herman MA et al.; When stationary phase cells of the dimorphic yeast Candida albicans are diluted into fresh medium at pH 4.5 (low pH), they synchronously form ellipsoidal buds, but when diluted into the same medium at pH 6.7 (high pH), they synchronously form elongate mycelia . Using a perfusion chamber to monitor single cells, we have compared the rates of volume growth between budding and mycelium-forming cells . Results are presented which demonstrate that: (1) after release from stationary phase into medium of low or high pH, each original sphere grows in volume to the time of initial evagination, but does not grow subsequently; (2) successive budding on the original mother cell occurs without interruption resulting in continuous volume growth; however, an interruption in volume growth of the initial bud (B1) occurs before it in turn evaginates; and (3) the rate of volume growth of the first bud at low pH is identical to the rate of volume growth of the mycelium at high pH even though the surface to volume ratios are quite different . The last result is unexpected and is therefore considered in relation to cell wall deposition. J Gen Microbiol, 1984 Sep, 130 ( Pt 9), 2213 - 8 The secretion of N-acetylglucosaminidase during germ-tube formation in Candida albicans; Sullivan PA et al.; N-Acetylglucosaminidase was induced by either N-acetylglucosamine or N-acetylmannosamine in several strains of Candida albicans . Enzyme activity was not induced in a N-acetylglucosamine non-utilizing mutant which is unable to express the first three steps in the N-acetylglucosamine catabolic pathway . The enzyme, purified 500-fold, had a specific activity of 36.8 units (mg protein)-1 and catalysed the hydrolysis of p-nitrophenyl-beta-n-acetylglucosamine, N,N'-diacetylchitobiose and N,N',N"-triacetylchitotriose . No activity was observed toward colloidal chitin, hyaluronic acid or mucin . The cellular distribution of N-acetylglucosaminidase was determined by measuring in situ enzyme activity before and after acid treatment of intact cells . N-Acetylglucosaminidase (80-88% of the total cellular activity) was rapidly secreted to the periplasm when the enzyme was induced either during yeast growth at 28 degrees C or germ-tube formation at 37 degrees C . Export of the enzyme from the periplasm into the medium was fourfold greater during germ-tube formation, and after 6 h incubation the amount of enzyme released into the medium represented 70% of cell-associated enzyme activity. Geburtshilfe Frauenheilkd, 1984 Sep, 44(9), 583 - 6 {Torulopsis in gynecology}; Mendling W; Torulopsis glabrata, a pathogenic yeast, causes a vulvovaginal mycosis in about 10% of all cases, whereas mostly candida albicans is identified . Yeasts of the genus Torulopsis seem to occur especially on healthy women, whereas in cases of the well-known risk factors the growth of Candida albicans is advanced . Torulopsidosis of the vagina commonly takes a mild course . The diagnosis is ensured only in cooperation with special laboratories . However, microscopic traps are absence of pseudomycelia and relatively small buds which contrast with the big buds of candida albicans . Although the clinical course is usually less heavy than in cases of candidosis, a six- to ten-day treatment with local imidazole or Polyene antimycotics is necessary to avoid recurrences . The fact that yeasts of the genus Torulopsis form no pseudomycelia is perhaps an explanation for the mostly mild course of illness on the one hand and for the weak response to cellwall-synthesis blocking antimycotics on the other hand. Mycopathologia, 1984 Aug 30, 87(1-2), 35 - 41 Cellular inactivation and mitotic recombination induced by ultraviolet radiation in aneuploid and euploid strains of Candida albicans; Rhoads DD et al.; Prototrophic aneuploid and euploid derivatives of wild type Candida albicans strains 207 were produced by fusing protoplasts of complementing auxotrophs obtained from strain 207 . Comparisons of cell survivals and incidences of mitotic recombinants occurring after ultraviolet irradiation (UV) of these strains indicate that (i) aneuploids are categorically less efficient than euploids for repair of pyrimidine dimers induced in DNA by UV and that (ii) such repair is enhanced by growing irradiated cells at 25 degrees C, on minimal medium or in the presence of ergosterol rather than at 37 degrees C, on amino acid enriched medium or medium unsupplemented with ergosterol . In addition, the comparisons establish than one cannot discriminate between strains of C . albicans which differ in cellular DNA contents or genomic constitutions on the basis of their UV survival curves. Mycopathologia, 1984 Aug 30, 87(1-2), 111 - 4 Prevalence of oral colonization with Candida albicans and anti-C . albicans IgA in the saliva of normal children and children with acute lymphoblastic leukaemia; Gentle TA et al.; The prevalence of oral colonization with C . albicans was studied in 40 children with acute lymphoblastic leukaemia (ALL) and 40 matched normal children . Colonization was more common in the ALL group (25% colonized) than the normal group (7.5% colonized) . Total saliva IgA levels were lower in the ALL group, but low levels did not correlate with oral colonization . The three normal children with oral colonization all had anti-C . albicans IgA in their saliva, as had seven of the ten colonized ALL patients. Mycopathologia, 1984 Aug 30, 87(1-2), 121 - 7 Broth dilution and disc diffusion methods in the susceptibility testing of pathogenic Candida albicans against four antimycotics; Kostiala AA et al.; Susceptibility of Candida albicans isolated from mouthrinse specimens during episodes of acute pseudomembranous candidiasis in patients with haematological malignancies was tested by the broth dilution and disc diffusion methods using 24 and 48 h of incubation . The time factor did not significantly affect the results with 5-fluorocytosine . With amphotericin B, prolonged incubation doubled the geometric mean MIC of C . albicans as well as the number of isolates with intermediate sensitivity . With the shorter incubation in the disc diffusion assay, few isolates showed lowered sensitivity to clotrimazole; at 48 h, however, this figure was as high as 54% . The yeasts were highly sensitive to ketoconazole at 24 h, whereas at 48 h the results were bizarre . At 24 h, correlations between disc diffusion and broth dilution methods were satisfactory, with clotrimazole and ketoconazole accounting for most of the discordancies . Accordingly, the disc diffusion results should be recorded at 24 h. S Afr Med J, 1984 Aug 4, 66(5), 173 - 7 Enhancement of human polymorphonuclear leucocyte motility by erythromycin in vitro and in vivo; Fernandes AC et al.; The effects of erythromycin on the migration, phagocytosis and antimicrobial activity of human polymorphonuclear leucocytes (PMNLs) were investigated in vitro . Therapeutic concentrations of erythromycin potentiated PMNL staphylocidal activity without affecting phagocytosis . PMNL random motility and migration to leuco-attractant endotoxin-activated serum (EAS) were significantly enhanced by erythromycin at concentrations of greater than 5 x 10(-5)M (16,5 micrograms/ml) . To assess the possible in vivo significance of these findings the same PMNL functions were investigated in healthy adult volunteers before and 90 minutes and 1 week after the ingestion of a single 500 mg tablet of erythromycin stearate . PMNL migration to EAS and antimicrobial activity were significantly increased after ingestion of erythromycin and eventually returned to normal levels . A single intraperitoneal injection of 1,5 mg erythromycin lactobionate significantly increased the mean survival time of mice experimentally infected with Candida albicans . These micro-organisms are resistant to the antimicrobial effects of erythromycin . These findings show that erythromycin possesses nonspecific immunopotentiating properties which may contribute to the antimicrobial activity of this antibiotic. J Immunol Methods, 1984 Aug 3, 72(1), 229 - 41 Flow cytometric assay for combined measurement of phagocytosis and intracellular killing of Candida albicans; Bjerknes R; A rapid quantitative flow cytometric (FCM) assay for the combined kinetic measurement of phagocytosis and intracellular killing of fluorescein-isothiocyanate (FITC) labelled Candida albicans is described . The fraction of phagocytosing leukocytes and the numbers of attached or internalized Candida albicans per phagocytosing leukocyte were quantified by FCM, using trypan blue and a fluorescence quenching technique . Results obtained by microscopy agreed with the FCM estimates of phagocytosis . Dead, but not live, Candida albicans stained by propidium iodide (PI) . Thus, both viable and intracellularly killed fungi could be discriminated and measured by FCM . Phagocyte killing determined by the FCM assay correlated with killing measured by a standard microbiological test and by methylene blue staining . The method allows rapid and accurate testing of opsonic and phagocytic functions under both experimental and clinical conditions. Helv Paediatr Acta, 1984 Aug, 39(3), 265 - 8 Early neonatal cutaneous candidiasis; Lopez-Linares M et al.; A premature female presented cutaneous lesions caused by Candida albicans at 12 h after delivery . Her mother carried Candida in the vagina . The lesions extended to face, both sides of the trunk and extremities, including palms and soles, and later to the mouth . The cutaneous manifestations healed in four weeks . It is proposed to use the term "early neonatal cutaneous candidiasis" to designate the forms of candidiasis which appear within the first hours after delivery, and "congenital cutaneous candidiasis" when lesions are present at delivery. J Infect Dis, 1984 Aug, 150(2), 278 - 83 Liposome-encapsulated amphotericin B for treatment of disseminated candidiasis in neutropenic mice; Lopez-Berestein G et al.; The relative efficacies of free amphotericin B (Amp B) and liposome-encapsulated Amp B (L-AmpB) in the treatment of established Candida albicans infection in mice rendered neutropenic with cyclophosphamide were studied . AmpB was entrapped in multilamellar liposomes composed of dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol in a molar ratio of 7:3 . Infected mice treated with single doses of 3 mg L-AmpB/kg of body weight had an increased survival time compared with those injected with either single (dose, 0.8 mg/kg) or multiple doses (dose, 0.8 mg/kg daily for five days) of free AmpB . When treatment was delayed beyond three days postinfection, neither single nor multiple doses of free AmpB resulted in increased survival, whereas treatment with single-dose L-AmpB (dose, 4 mg/kg) showed efficacy when delayed as much as four days postinfection . Five days postinfection only higher doses (dose, 5.6 mg-11.2 mg/kg) of L-AmpB improved survival time and the renal impairment present in the infected animals . These data provided a rational basis for using high-dose L-AmpB to treat fungal diseases in humans, particularly in neutropenic patients. Isr J Med Sci, 1984 Aug, 20(8), 711 - 4 Candidemia and sternal Candida albicans osteomyelitis in a patient with chronic lymphatic leukemia; Estrov Z et al.; Sternal osteomyelitis caused by Candida albicans without previous surgery or trauma occurred in a patient with chronic lymphatic leukemia and recurrent skin cancer . The osteomyelitic process healed without antifungal treatment . Three weeks later, following a radical neck dissection, candidemia, without recurrence of the osteomyelitis, was diagnosed and treated successfully with intravenous amphotericin B and 5-fluorocytosin . The presentation of Candida osteomyelitis as a manifestation of disseminated candidiasis in immunocompromised hosts is discussed and the relevant literature is briefly reviewed. J Oral Pathol, 1984 Aug, 13(4), 390 - 3 The oral carriage of yeasts and coliforms in patients on cytotoxic therapy; Samaranayake LP et al.; The oral carriage of yeasts and coliforms in a healthy adult population and a group of patients with malignancies, undergoing cytotoxic therapy was investigated . A quantitative increase in the intra-oral carriage of Candida species and coliforms was observed during cytotoxic therapy . The most frequent yeast and the coliform isolated were Candida albicans and Escherichia coli, respectively . Thus, the oral cavity may constitute a reservoir of potentially pathogenic flora in patients on cytotoxic therapy. J Gen Microbiol, 1984 Aug, 130 ( Pt 8), 1941 - 5 Magnesium and the regulation of germ-tube formation in Candida albicans; Walker GM et al.; Candida albicans requires Mg2+ for germ-tube formation . Mg-deficient media, metal ion chelators and the ionophore A23187 inhibited germ-tube formation . Cell Mg content during exponential yeast-phase growth remained constant but increased throughout germ-tube formation . The onset of germ-tube formation coincided with a sharp peak in Mg concentration within the cells . Yeast-phase cells of strain CA2, which did not form germ-tubes, had a lower Mg content and failed to accumulate Mg when incubated under conditions for germ-tube formation . Mg also increased the uptake and incorporation of N-acetylglucosamine . These findings point to a central regulatory role for Mg in C . albicans morphogenesis. Can J Microbiol, 1984 Aug, 30(8), 1001 - 7 Adherence of Candida albicans to buccal and vaginal epithelial cells: ultrastructural observations; Calderone RA et al.; The adherence of Candida albicans to human buccal and vaginal epithelial cells was studied by transmission electron microscopy . Adherence to epithelial cells was confirmed by both a radiometric assay as well as direct microscopic examination of stained cell preparations . Ultramicroscopic preparations revealed that yeast cells were closely appressed to epithelial cell surfaces and were often partially enclosed within phagocyticlike invaginations of the epithelial cells . A murine model of vaginitis caused by C . albicans was also used to study adherence to epithelial cells and to follow the course of colonization . Ultramicroscopic preparations of murine vaginal tissue revealed that within 2 h postinfection, yeast cells could be seen adhering to epithelial cells . At 6 h postinfection, hyphae and yeast cells were not only found on the epithelial cell surface but also within the submucosal tissue . When observed on the epithelial cell surface, Candida cells were either attached to host cells, or when infected tissue was stained with ruthenium red, Candida cells were observed on the epithelial surface embedded within an electron-dense matrix . Fungal elements were abundant in the submucosa at 24 h postinfection and were still observed on the epithelial cell surface; all of this was accompanied by an inflammatory response. J Prosthet Dent, 1984 Aug, 52(2), 305 - 7 An alternative to conventional overdenture attachments with Molloplast-B: a technique; Shernoff AF et al.; The use of Molloplast-B within the abutments of mandibular overdentures is an easy and inexpensive method for increasing retention and stability of dentures . The use of a retentive area prepared in natural tooth structure increases retentive capabilities for the overdenture patient . Unlike some silicone denture liners, Molloplast-B has shown an inhibitory effect to the growth of Candida albicans . Molloplast-B can be used in the conventional overdenture method or as described for an immediate overdenture . This type of overdenture can be relined easily to adjust for changes in mouth architecture . How well this material will retain its shape and consistency needs to be observed. Clin Exp Immunol, 1984 Aug, 57(2), 307 - 14 The role of complement and antibody in opsonization and intracellular killing of Candida albicans; Pereira HA et al.; The purpose of this investigation was two-fold . The first, to explore the relationship between ingestion (measured by the phagocytic index method), iodination (measured by the neutrophil iodination micromethod) and intracellular killing (measured by the methylene blue test) of Candida albicans by human polymorphonuclear leucocytes . The second, to determine the effects of complement and antibody on ingestion and intracellular killing of C . albicans . Optimal phagocytosis of C . albicans was observed in fresh untreated human serum . Phagocytosis was present but reduced, in serum depleted of either antibody (by absorption) or complement (by heating at 56 degrees C for 30 min) . Whilst in the complete absence of serum, or in FCS the levels were reduced still further . The percentage killed of ingested C . albicans remained constant irrespective of the number of organisms ingested, thus the greater the number ingested, the greater the number killed . Maximal intracellular killing expressed as a percentage of ingested Candida occurred in fresh untreated serum . Intracellular killing did occur in heat-inactivated serum and absorbed serum, although the levels were significantly reduced . The results suggest that C . albicans opsonized in fresh normal PHS are phagocytosed as well as killed more efficiently than those opsonized with only complement or antibody. Cancer Res, 1984 Aug, 44(8), 3467 - 70 Inhibition of mitogen- and antigen-induced lymphocyte activation by human leukemia cell gangliosides; Gonwa TA et al.; Human leukemia cell gangliosides were found to inhibit in vitro activation of human lymphocytes by lectins and the soluble antigen Candida albicans at concentrations as low as 2 micrograms/2 X 10(5) lymphocytes/0.2-ml cultures . The inhibition was not due to a reduction in the number of viable cells, but to an inhibition of blast formation . Three gangliosides were purified from the original mixture and tested for their ability to inhibit in vitro activation of lymphocytes . All 3 gangliosides inhibited lymphocyte activation to a similar degree when tested over a concentration range of 5 to 100 micrograms per ml of culture . Removal of sialic acid from the gangliosides by neuraminidase treatment significantly reduced or abolished their inhibitory effect . The gangliosides used in our analyses are not unique to leukemia cells . However, their concentration is increased in patients with cancers . Therefore, our results demonstrate that gangliosides isolated from human leukemia cells can inhibit lymphocyte activation when added in concentrations equivalent to those found in sera of patients with leukemia and other cancers. Br J Rheumatol, 1984 Aug, 23(3), 198 - 202 A radiometric assessment of phagocytosis and intracellular killing by blood polymorphonuclear leucocytes in rheumatoid arthritis; Sheehan NJ et al.; Disagreement persists about the phagocytic function of blood polymorphonuclear leucocytes (PMN) in rheumatoid arthritis (RA) . Many of the experimental data have been generated by subjective methods of assessment . Using a radiometric assay, we found no difference in the phagocytosis and intracellular killing of Candida albicans by blood PMN from 18 patients with RA when compared with PMN from 21 healthy control subjects . We infer that the increased incidence of non-articular infection reported in RA is not related to impaired phagocytic function of blood PMN. Boll Soc Ital Biol Sper, 1984 Jul 31, 60(7), 1415 - 9 {Pathogenicity of various species of Candida in an experimental murine system}; Perito S et al.; The systemic infection induced by Candida albicans, Candida krusei and Candida viswanathii was studied in an experimental murine system . Candida albicans is able to kill outbred CD1 mice within a few days and at a very low concentration; C . krusei is not pathogenic not even when inoculated at a higher concentration; C . viswanathii is able to kill animals only a a higher concentration . The different resistances do not seem to be under genic control, in as much as the different strains of mice used (hybrid CD2F1 and B6C3HF1, inbred Balb/c) show the same degree of resistance as the CD1 mice to the three species of Candida . The colony forming units (CFU) in the kidneys of CD1 mice inoculated intravenously with 10(5) cells of the three species of Candida, collected at various intervals showed a good correlation with the median survival times: a rapid moltiplication of the C . albicans is evident in the kidneys of the animals 24 hours after the inoculation, while the C . krusei and the C . viswanathii do not moltiply. Biochim Biophys Acta, 1984 Jul 26, 794(3), 466 - 71 Properties of a particulate squalene epoxidase from Candida albicans; Ryder NS et al.; The properties and requirements of squalene epoxidase and effects of some inhibitors were investigated in the pathogenic yeast Candida albicans . A washed 'microsomal' fraction converted radiolabelled squalene to 2,3-oxidosqualene and lanosterol . Minimum requirements for activity were molecular oxygen, NADH or NADPH, and FAD . Epoxidase activity was stimulated by up to 100% by addition of the soluble cytoplasmic fraction, which itself contained negligible epoxidase activity . This stimulation was most powerful at low concentrations of enzyme, or high concentrations of squalene . Divalent cations did not stimulate activity and EDTA was not inhibitory . An apparent Km for squalene of 50 microM was determined in the presence of soluble cytoplasm . Epoxidase activity was destroyed by Triton X-100, deoxycholate or Cu2+, and partially inhibited by thiol reagents, rotenone and antimycin A . The enzyme was not inhibited by cyanide or by several inhibitors of cytochrome P-450. FEBS Lett, 1984 Jul 23, 173(1), 134 - 8 Echinocandin inhibition of 1,3-beta-D-glucan synthase from Candida albicans; Sawistowska-Schroder ET et al.; The cyclic peptide antibiotic echinocandin was found to inhibit 1,3-beta-D-glucan synthase activity present in a mixed membrane fraction from Candida albicans . Addition of antibiotic reduced the Vmax of the enzyme, but the Km was unaffected . GTP stimulated enzyme activity approximately 4-fold, but did not affect the percentage inhibition of the enzyme by echinocandin . Treatment of the reaction products with alpha-amylase and beta-glucanase confirmed that the polymer synthesised was 1,3-beta-D-glucan, not glycogen. Clin Exp Immunol, 1984 Jul, 57(1), 178 - 86 Regulation by muramyl dipeptide (MDP) of the lymphoproliferative responses and polyclonal activation of human peripheral blood mononuclear cells; Bahr GM et al.; The ability of muramyl dipeptide (MDP), its adjuvant inactive stereoisomer, MDP(D-D), and the non-pyrogenic, adjuvant active analogue, MDP-butyl ester (MDP-BE), to induce in vitro proliferation and/or polyclonal activation (PA) of peripheral blood mononuclear cells (PBMNC) from normal volunteers, was studied . MDP, as well as its two analogues, were incapable of inducing 3H-thymidine uptake or immunoglobulin synthesis in PBMNC cultures from the majority of the individuals tested . However, these muramyl peptides were capable of regulating the in vitro proliferative responses of some individuals to concanavalin A and to soluble antigens of Candida albicans . At the same time, enhancement of the pokeweed mitogen-induced IgA and IgM but not IgG PA was observed with MDP, its adjuvant active analogue MDP-BE, but not with the adjuvant inactive stereoisomer MDP(D-D) . Results are discussed with relation to a possible genetic restriction of the responsiveness to MDP. Invest Ophthalmol Vis Sci, 1984 Jul, 25(7), 851 - 4 Efficacy of antifungal agents in the cornea . IV . Amphotericin B methyl ester; O'Day DM et al.; Quantitative mycologic techniques were used to evaluate the efficacy of topical amphotericin B methyl ester in two models of yeast infection in rabbit eyes . Doses of 1%, 0.5%, and 0.15% were used in a model of superficial Candida albicans infection . The 1% dose of drug was highly efficacious, abolishing the disease after 2 days of treatment . With doses of 0.5% and 0.15%, decreasing efficacy was observed . Antifungal activity did not deteriorate when 1% prednisolone acetate was administered concomitantly with the 1% dose . In a model of deep stromal infection, the administration of topical 1% amphotericin B methyl ester was highly efficacious when the corneal epithelium was absent . Even in corneas with intact epithelium, a reduced though still significant effect was noted. J Antimicrob Chemother, 1984 Jul, 14(1), 41 - 50 Studies on the effects of ingestion of a single 500 mg oral dose of erythromycin stearate on leucocyte motility and transformation and on release in vitro of prostaglandin E2 by stimulated leucocytes; Anderson R et al.; Polymorphonuclear leucocyte (PMNL) and mononuclear leucocyte (MNL) migration to the leucoattractant endotoxin-activated serum as well as MNL mitogen-induced transformation were measured in normal adult volunteers before and 1 1/2 h and 96 h after the ingestion of a single oral dose of 500 mg of erythromycin stearate . Ingestion of the antibiotic was associated with a significant increase in PMNL migration at 1 1/2 h with a return to normal levels at 96 h . Slight but insignificant enhancement of MNL migration and of transformation to mitogens was detected after erythromycin . The mechanism of the slight stimulation of MNL transformation, which was consistently observed, was investigated further in vitro by measuring the effects of erythromycin base on the release of prostaglandin (PG) E2 by mitogen-stimulated MNL . Similar studies were performed using leuco-attractant-exposed PMNL . Inhibition of PGE2 release was observed for both MNL and PMNL with therapeutic concentrations of erythromycin . To assess the possible in-vivo significance of the immunopotentiating properties of the antibiotic the effect of a single intraperitoneal injection of 250, 500 or 1000 micrograms on the survival time of mice lethally infected with the erythromycin-resistant microorganism Candida albicans were investigated . Pre-treatment of the mice with erythromycin at each concentration used significantly increased the mean survival times . It is possible that these non-specific immunostimulatory properties of erythromycin potentiate in-vivo antimicrobial activity. Antimicrob Agents Chemother, 1984 Jul, 26(1), 108 - 9 Ornithyl amphotericin methyl ester treatment of experimental candidiasis in rats; Galgiani JN et al.; After intravenous Candida albicans infection, rats received orinthyl amphotericin methyl ester, amphotericin B, or diluent intravenously . At doses of 0.1 and 0.5 mg/kg, the drugs were equally effective in preventing deaths . However, at doses of 2.0 mg/kg, mortality after treatment with amphotericin B was greater than that after placebo, whereas orinthyl amphotericin methyl ester was fully protective. Zentralbl Bakteriol Mikrobiol Hyg {A}, 1984 Jul, 257(2), 266 - 74 A variety of Candida proteinases and their possible targets of proteolytic attack in the host; Ruchel R; Acid proteinases are secreted by the majority of strains of Candida albicans, C . tropicalis and C . parapsilosis, reflecting the sequence of virulence of Candida spp . for man . As revealed by exposure to various substrates and inhibitors, Candida proteinases are strain-specific, although close relationships exist between enzymes from strains of the same species . Possible targets of hydrolytic attack by Candida proteinases in the host are immunoglobulins, the proteinase scavenger alpha-2-macroglobulin, zymogens of regulatory serine proteinases such as coagulation factor X, and angiotensinogen . The involvement of Candida proteinase in the pathogenesis of acronecrosis is discussed. Zentralbl Bakteriol Mikrobiol Hyg {A}, 1984 Jul, 257(2), 257 - 65 Attachment of Candida to mammalian tissues--clinical and experimental studies; Segal E et al.; In this study we investigated whether a correlation between the frequency of candidal vaginitis and in vitro adherence of Candida albicans to human vaginal epithelial cells exists . The in vitro adherence of C . albicans to epithelial cells collected from 347 women of fertility and postmenopausal age, who did not suffer from vaginitis was assessed microscopically . Epithelial cells from women of the groups with known high frequency of vaginitis: diabetic and pregnant women revealed increased ability of in vitro adherence in comparison with a control group . We also investigated whether a correlation between the hormonal status of the women and adherence capacity of the epithelial cells exists . In vivo attachment of C . albicans to epithelial cells was studied in an experimental murine vaginitis model and assessed histopathologically in tissue sections or microscopically in mounts of exfoliated cells . Attempts were made to block the in vivo attachment and prevent infection by pretreating the animals with substances analogous to the fungal cell walls: substances which were previously found to be inhibitory in the in vitro adherence assay . Chitin, its component - N-acetylglucosamine (NAG) and a soluble extract derived from chitin (CSE) inhibited in vivo attachment and prevented infection. Antimicrob Agents Chemother, 1984 Jul, 26(1), 74 - 7 Enhanced killing of Candida albicans by cultured peritoneal exudate cells treated with SM-1213, a synthetic immunomodulator; Morrison CJ et al.; The effect of SM-1213 {1,2-O-isopropylidene-3-O-3'-(N', N'-dimethylamino-n-propyl)-D-glucofuranose} on the candidastatic and candidacidal capacity of guinea pig peritoneal exudate cells was investigated . Phagocytes treated with SM-1213 demonstrated an enhanced ability to inhibit intracellular hyphal formation and elongation of Candida albicans cells as well as to reduce the percentage of viable cells remaining after phagocytosis . Significant drug-induced anticandidal effects were also observed when peritoneal exudate cells were preincubated with SM-1213 and washed before infection with C . albicans . SM-1213 had no direct anticandidal effect against the yeast or hyphal form of the fungus, suggesting that the observed candidastatic and candidacidal effect of this drug was due to the enhancement of antimicrobial functions of phagocytes. J Gen Microbiol, 1984 Jul, 130 ( Pt 7), 1857 - 61 The detection and analysis of chitinase activity from the yeast form of Candida albicans; Barrett-Bee K et al.; Chitinase activity was detected in the supernatant fraction of a high-speed centrifugation preparation of broken Candida albicans yeast cells . The enzyme showed peak activity during the rapid budding phase of growth and was found to parallel the chitin synthase activity . The optimum conditions for the hydrolysis of chitin, regenerated from acetylation of chitosan, were determined . Analysis of the kinetics of the enzyme-substrate interaction and a measurement of their binding suggests that an equilibrium binding situation exists and that the kinetics follow a Langmuir isotherm interaction. Infect Immun, 1984 Jul, 45(1), 74 - 81 Demonstration and solubilization of antigens expressed primarily on the surfaces of Candida albicans germ tubes; Smail EH et al.; Antisera against mycelial-phase, but not yeast-phase, Candida albicans absorbed with yeast-phase organisms preferentially stained germ tube segments of several strains of mycelial-phase C . albicans by the indirect fluorescent-antibody staining technique . Germ tube segment antigens were not found in significant amounts on blastospore segments or on yeast-phase organisms . Absorption of the mycelial-phase reference sera with yeast-phase C . stellatoidea, but not with C . tropicalis, C . guillermondii, or Saccharomyces cerevisiae, resulted in preferential germ tube segment staining of C . albicans . A dithiothreitol extract of mycelial-phase C . albicans organisms blocked staining of the germ tube segment, but a dithiothreitol extract of yeast-phase organisms did not . When dithiothreitol extracts from both phases were reacted against yeast-absorbed reference sera in tandem crossed and crossed line immunoelectrophoresis, a cross-reacting arc and several arcs unique to the mycelial-phase extract were noted . Immunofluorescent staining tests were performed, using appropriately absorbed sera from patients with candidiasis to stain a laboratory strain of C . albicans . Human tissue slices infected with C . albicans were used as targets for appropriately absorbed rabbit antisera . These human data indicated that antigens preferentially expressed on the germ tube in vitro were also expressed on filamentous structures of the fungus in infected human tissues . In vitro and in vivo, the invasive mycelial phase of C . albicans expresses certain antigens that are highly concentrated on the germ tube. Infect Immun, 1984 Jul, 45(1), 6 - 12 Relationship between cell surface composition, adherence, and virulence of Candida albicans; McCourtie J et al.; A comparison was made of the adherence to acrylic and to human buccal epithelial cells of seven strains of Candida albicans isolated from active infections (I strains) and two strains obtained from asymptomatic carriers (C strains) . After growth in defined medium containing a relatively low concentration (50 mM) of glucose as the carbon source, the adherence of I and C strains to either surface was similar and all strains were sensitive to spheroplast formation with Zymolyase 5000 . Growth in medium containing a high concentration (500 mM) of sucrose or galactose enhanced the adherence of I strains up to 5- and 11-fold, respectively, and there were corresponding increases in resistance to spheroplast formation . Sucrose- or galactose-grown C strains showed only small increases in adherence and remained relatively sensitive to spheroplast formation . When inoculated intravenously into mice, I strains grown in 500 mM sucrose were up to five times more virulent than organisms grown in 50 mM glucose, while I strains grown in 500 mM galactose showed a 5- to 24-fold increase in virulence . Fifty percent lethal doses obtained for C strains were similar after growth on all three carbon sources . We conclude that I strains are able to modify their surface composition in response to high concentrations of certain sugars in the growth environment . Such modification can enhance both their ability to adhere to surfaces and their virulence . C strains lack this capability, or possess it to a lower degree, and may therefore have a lower pathogenic potential. Blood, 1984 Jul, 64(1), 147 - 51 Heterogeneity of human neutrophil phagolysosomes: functional consequences for candidacidal activity; Cech P et al.; Opsonized yeast phase Candida albicans, incubated with human neutrophils, are internalized into two classes of phagosomes . One class, termed "unsealed vacuoles," comprises approximately 40% of the total and maintains functional communication to the cell's exterior that is sufficient to permit ingress of dyes, such as trypan or methylene blue . The remaining cell-associated yeasts are contained in "sealed vacuoles," completely sequestered from the external milieu . Approximately 71.8% of C albicans within sealed vacuoles are rendered nonviable within 60 minutes, whereas only 14.5% of organisms within unsealed vacuoles are killed during this time . We conclude that vacuolar sealing mechanisms are imperfectly developed in normal human neutrophils and that incompletely sealed vacuoles support antimicrobial processes substantially less well than do completely sealed ones. J Immunol, 1984 Jul, 133(1), 202 - 7 Mononuclear cell-mediated enhancement of granulocyte function in man; Vadas MA et al.; Human monocyte-enriched mononuclear cells (MNC) (greater than 95% monocytes) powerfully stimulated the antibody-dependent killing of tumor cells by purified human neutrophils (NE) or eosinophils (EO) . The enhancement was observed when the mononuclear cell to granulocyte ratio was as low as 1:100 . Media conditioned by MNC also stimulated antibody-dependent killing by NE and EO as well as the uptake and killing of Candida albicans by NE . There was a heterogeneity amongst individuals in the capacity of their MNC to elaborate this factor, and approximately 15% of individuals did not produce detectable factor . Different factors in the MNC supernatant were involved in NE and EO activation . The EO-activating factor (AF) had a m.w . of approximately 27,000 and migrated as a single band on phenyl-Sepharose chromatography . The NE-AF had a m.w . of 22,000 and migrated as two distinct bands on phenyl-Sepharose chromatography . EO-colony-stimulating factor (CSF) co-purified with EO-AF, and granulocyte-macrophage-CSF co-purified with both bands of NE-AF . It is concluded that MNC elaborate CSF-like molecules that powerfully stimulate human granulocyte function. Invest Ophthalmol Vis Sci, 1984 Jul, 25(7), 855 - 9 Influence of the corneal epithelium on the efficacy of topical antifungal agents; O'Day DM et al.; A model of deep stromal Candida albicans infection was established by injecting 25 microliters of a suspension containing 5 X 10(9) colony forming units/ml of the yeast into corneas of pigmented rabbits . In this model, the infection lasts for more than 8 days . Using quantitative techniques, the authors compared the efficacy of six topical antifungal agents in the presence of an intact epithelium and in corneas debrided of epithelium . In corneas debrided on a daily basis, the polyenes (amphotericin B 0.15% and 0.075% and natamycin 5%) exhibited a significant antifungal effect . When the epithelium was left intact, 5% natamycin and 0.075% amphotericin B were without effect, while the efficacy of the 0.15% preparation of amphotericin B was much reduced . Removal of the epithelium appeared to affect adversely the efficacy of flucytosine . The imidazoles were not efficacious in this model. J Invest Dermatol, 1984 Jul, 83(1), 32 - 6 Isolation and characterization of proteinase from Candida albicans: substrate specificity; Negi M et al.; Candida albicans was able to produce a keratinolytic proteinase (KPase) when cultivated in a medium containing human stratum corneum as a nitrogen source . The KPase was purified to 108.5-fold by ion-exchange chromatography and gel filtration . The molecular weight of the enzyme was estimated to be 42,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and gel filtration through Sephacryl S-200, while the isoelectric point was determined to be at pH 4.5 . The enzyme had an optimum pH of 4.0 and was "inactive" below pH 2.5 and above pH 6.0 . The activity of KPase after preincubation at various temperatures was stable up to 50 degrees C . The keratinolytic activity was not affected by the addition of nonionic detergents and divalent cations . The enzyme was a glycoprotein and contained a high content of aspartic acid residues (172/1000) . Pepstatin and chymostatin inhibited the activity in a dose-dependent manner; however, neither the other group specific inhibitors tested nor the pepsin specific inhibitors, DAN or EPNP, showed any effect on the enzyme . From these inhibitory profiles, this enzyme was determined to be a carboxyl proteinase such as cathepsin D . Among the various substrates for proteolytic enzymes, KPase digested human stratum corneum as much as albumin and hemoglobin . In the three fractions (water soluble, keratin filamentous, and membranous) prepared from human stratum corneum, the keratin filamentous fraction was more susceptible to degradation by KPase than the other two fractions were . KPase also digested much less human fingernail (13%) than human stratum corneum, but did not show any signs of there being any digestion of human scalp hair . These studies suggest that KPase from C . albicans may play an important role in superficial infection by affecting the human stratum corneum of the skin and nail. Antimicrob Agents Chemother, 1984 Jul, 26(1), 22 - 5 Direct membrane-damaging effect of ketoconazole and tioconazole on Candida albicans demonstrated by bioluminescent assay of ATP; Ansehn S et al.; Bioluminescent assays of fungal ATP in cultures of Candida albicans exposed to tioconazole and ketoconazole demonstrated that intracellular ATP levels were directly related to cell viability . At high concentrations of drug, a fungicidal effect was indicated by a very rapid and heavy leakage of ATP and a simultaneous, dramatic decrease in intracellular ATP . This leakage was due to direct membrane damage, which was less pronounced after exposure to ketoconazole than to tioconazole . After exposure to lower imidazole concentrations, intracellular ATP indicated growth inhibition without significant leakage of ATP . These findings support the hypothesis that imidazole antifungal agents basically act in the same manner but at different concentrations. Clin Exp Rheumatol, 1984 Jul-Sep, 2(3), 253 - 7 Immunologic safety of ibuprofen in rheumatoid arthritis: preliminary evidence; Jorizzo JL et al.; Some evidence indicates that ibuprofen and other prostaglandin synthetase inhibitors may have the potential for cellular immune enhancement in addition to their anti-inflammatory activity . If this is true, treatment of rheumatoid arthritis, a disorder of presumed autoimmune pathogenesis, would present a dilemma . These agents are widely used in rheumatoid arthritis for their anti-inflammatory effects . If they are found to enhance cellular immune function, however, the disease might be stimulated over the long term, rather than suppressed . Preliminary evidence from four patients with rheumatoid arthritis show that oral ibuprofen had no significant immunologic effect during sequential "on" and "off" cycles, as assessed by the following measures: delayed hypersensitivity skin testing; lymphocyte transformation to mitogen (phytohemagglutinin) or specific antigen (Candida albicans); T-cell subsets, as determined by monoclonal antibody techniques; or production of the lymphokine, human immune interferon, in response to phytohemagglutinin or to staphylococcal enterotoxin A . Early evidence, therefore, suggests that oral ibuprofen therapy may be 'immunologically safe' in patients with rheumatoid arthritis, but investigations of large series of patients also assessing local immune reaction in diseased joints may be necessary for confirmation. Med J Aust, 1984 Jun 23, 140(13), 780 - 1 Role of the lemon in disseminated candidiasis of heroin abusers; Newton-John HF et al.; The occurrence of several small outbreaks of disseminated candidiasis among heroin abusers in Australia suggests that a common source for infection was present in each incident . Because in all outbreaks so far described lemon juice has been used to dissolve heroin powder before injection, we decided to examine the ability of lemon juice to support the growth of Candida albicans . Lemons which were experimentally inoculated with small numbers of C . albicans promoted the rapid growth of the organism at room temperature . We propose that clinical infection results from the intravenous injection of a large inoculum of C . albicans from contaminated lemon juice . This is supported by the simultaneous occurrence of the disease in three drug abusers . We also propose that the lemon was contaminated by the heroin abusers, as disseminated candidiasis occurred only after the lemon was used a second time after being left at room temperature for one week. J Laryngol Otol, 1984 Jun, 98(6), 609 - 11 'Candida infection in the tongue and pharynx'; Bassiouny A et al.; 60 patients with chronic pharyngitis were investigated . In all cases the tongue was coated, fissured or hairy . Scrapings from the tongue and swabs from the posteriors pharyngeal wall were examined for the presence of Candida albicans . In the tongue cultures were positive in all cases, and in the pharynx they were positive in 42 cases . After treatment with 'Canasten' solution, the condition was cured in 53 cases . This directs attention to the role of Candida albicans as a cause of chronic pharyngitis, and to the relationship between candidiasis of the tongue and that of the throat. Int J Oral Surg, 1984 Jun, 13(3), 226 - 38 Candida in patients with oral lichen planus; Lundstrom IM et al.; The presence of yeasts in oral lichen planus (OLP) lesions was studied in cultivations from 41 OLP patients and by histological examination in 39 of these cases . The histological features of OLP were also recorded . The cultivation results were compared with those of a randomly selected, age- and sex-matched control group without mucosal changes . The extent of growth was recorded as "sparse" (1-10 colonies), "model-rate" (11-40 colonies), or "heavy" (greater than 40 colonies) . Yeasts were found to be present on cultures or histologic sections from a total of 19 OLP patients (46%) . "Moderate-heavy" growth was obtained in 29% of the OLP cases but in only 7% of the control group . Candida albicans accounted for over 80% of the yeasts . The histological examination revealed only 3 cases of invasive fungal growth . Regarding the criteria of OLP, hyperortho- or hyperparakeratosis and a band-shaped subepithelial infiltration of lymphocytes were present in all specimens, basilar liquefaction degeneration in 87% and an eosinophilic zone in 77% . Local treatment with amphotericin B (Fungizone) in 18 OLP patients with positive findings resulted in subjective relief of symptoms in 89% of the patients . Clinical improvement was seen in 94% . The presence of Candida was significantly correlated to low secretion rate in unstimulated saliva. J Oral Pathol, 1984 Jun, 13(3), 265 - 70 Effects of smoking on the prevalence and intraoral distribution of Candida albicans; Oliver DE et al.; To find out whether smoking affects the prevalence and intraoral distribution of Candida albicans, swabs and saliva samples from 100 healthy persons, smokers and non-smokers were cultured for the presence of this fungus . The prevalence was the same (35%) in both smokers and non-smokers . Among carriers, the mean concentration of C . albicans colony-forming units in saliva of smokers was twice that of the non-smokers, and the isolation frequency of C . albicans at each of 5 mucosal sites was also higher in smokers than in non-smokers . However, a wide variation was found, and these differences were not significant at the 0.05 level . Men were carriers more often than women (p less than 0.025), and the mucosal site from which C . albicans was recovered most often was the posterior dorsum of the tongue . Although it has previously been claimed that cigarette smoking influences the carrier state of C . albicans, the present study suggests that the effect is only slight. Can J Microbiol, 1984 Jun, 30(6), 857 - 63 The effect of aculeacin A and papulacandin B on morphology and cell wall ultrastructure in Candida albicans; Bozzola JJ et al.; Transmission (TEM) and scanning electron microscopy (SEM) of Candida albicans cultures treated with the cell wall active antibiotics aculeacin A and papulacandin B (10 micrograms/mL) revealed highly distorted, wrinkled, and collapsed cells . Dividing cells failed to separate properly and aggregates of enlarged and elongated forms were often seen . TEM sections revealed thick and layered cell walls in the treated cultures and bud cross walls failed to segregate completely . Approximately 20% of the cells demonstrated complete cell necrosis accompanied with cytoplasmic deterioration, layered and distorted walls, and improperly formed buds and scars. J Clin Microbiol, 1984 Jun, 19(6), 804 - 12 Comparison of serum mannan, arabinitol, and mannose in experimental disseminated candidiasis; de Repentigny L et al.; Concentrations of arabinitol, mannose, and mannan in serum have independently been reported to be elevated in patients with invasive candidiasis . These three marker substances were compared in a rabbit model . Twelve rabbits, immunosuppressed with cortisone, were infected intravenously with Candida albicans 3181A . Six uninfected control animals also received cortisone, and four rabbits were neither infected nor immunosuppressed . Blood samples, drawn from 2 days before to 14 days after infection, were assayed for serum mannan by sandwich enzyme immunoassay, antibodies to mannan by indirect enzyme immunoassay, arabinitol and mannose by gas-liquid chromatography, and serum creatinine . Serum mannan, negative before infection, peaked in all infected animals 4 days after infection (mean, 18 ng/ml) and decreased thereafter . Significant increases (2 standard deviations greater than mean in normals) in arabinitol, the arabinitol/creatinine ratio, and mannose were found in 12, 8, and 12 of the infected rabbits, respectively, but also in all 6 uninfected animals receiving cortisone . Only serum mannan was specific in this immunosuppressed rabbit model. J Antimicrob Chemother, 1984 Jun, 13(6), 547 - 58 In-vitro resistance to imidazole antifungals in Candida albicans; Johnson EM et al.; Three strains of Candida albicans from patients with chronic mucocutaneous candidosis (CMC) who relapsed during prolonged treatment with ketoconazole were compared with three other Can . albicans strains by means of an agar incorporation MIC method, a broth microdilution method for IC30 determination, and a hyphal elongation assessment method . The MICs of ketoconazole, tioconazole and miconazole were difficult to interpret, but were much higher for the three CMC strains if low inoculum concentrations and short incubation times were used . The IC30S of the three imidazoles were much higher for the CMC strains than for the others . The imidazoles all caused minimal inhibition of hyphal elongation by the three CMC strains at concentrations up to 50 mg/l . Concentrations of 0.5 mg/l caused marked inhibition of the other strains. Farmaco {Sci}, 1984 Jun, 39(6), 514 - 23 {N-substituted p-fluorobenzene sulfonamides with antimicrobial activity . I}; Vigorita MG et al.; In an extension of the investigations on fluorine derivatives of potential pharmacological interest, some new p-fluorobenzensulfonanilides were synthesized and screened in vitro against many species of Gram-positive and Gram-negative bacteria and against some strains of Candida albicans . Some of these compounds exhibited significant antibacterial activity . The relation between activity and structure revealed that the presence of chloro and trifluoromethyl groups in the aniline ring increases activity against Gram-positive bacteria . The acute toxicity in mice was also determined. Appl Environ Microbiol, 1984 Jun, 47(6), 1341 - 2 Factors affecting spore formation in a Candida albicans strain; Montazeri M et al.; Growth and spore formation of Candida albicans Y-45 was enhanced by low oxygen tension . Mycelium and chlamydospores were abundantly found on rice infusion-Tween 80 agar within 48 to 96 h, and abundant chlamdospore production occurred most rapidly under reduced oxygen tension and incubation at 30 degrees C . Zn, Mg, Mn, anf Fe were tested for their ability to promote filamentation in C . albicans Y-45 . Filamentation under conditions of low Mg and high Mn suggested that morphogenesis is possibly correlated with the presence of salts of these heavy metals. J Infect Dis, 1984 Jun, 149(6), 986 - 97 Interaction of plasma proteins and lipoproteins with amphotericin B; Brajtburg J et al.; Amphotericin B (AmB) binds to the cholesterol in lipoproteins, as determined by comigration in density gradient ultracentrifugation and changes in the circular dichroic spectrum . The saturation curve and Scatchard plots obtained with circular dichroism suggest that four to 10 cholesterol molecules in low-density lipoproteins bind to one molecule of AmB . AmB interacts more rapidly with low- and very-low-density lipoproteins than with high-density lipoproteins, but the circular dichroic spectrum of the complexed species is the same in all three cases . AmB also binds to other proteins in blood, but much higher concentrations of these proteins than of lipoproteins are needed for comparable binding . Interaction with lipoproteins stabilizes the antifungal activity of AmB . Interaction with lipoproteins and with much higher concentrations of other proteins in blood can also inhibit the effects of AmB on red blood cells, which contain cholesterol in their plasma membranes, but not the effects on Candida albicans, whose membranes contain ergosterol . An appropriate inference is that, when used clinically, AmB circulates in blood bound to lipoproteins and other proteins . The toxic and therapeutic effects of AmB in clinical situations are thus contingent on competitive interactions between sterol-containing cellular membranes of the host and the parasite and components of blood, such as lipoproteins and proteins. Infect Immun, 1984 Jun, 44(3), 702 - 7 Fungistatic and fungicidal activity of human parotid salivary histidine-rich polypeptides on Candida albicans; Pollock JJ et al.; Human parotid saliva histidine-rich polypeptides exerted antifungal activity against Candida albicans at concentrations similar to the known antifungal activity of the imidazole antibiotics . Inhibition of both growth and viability could be demonstrated by optical density monitoring and plating assays . Inhibition of growth was observed to be greatest when the histidine-rich polypeptides were added to the inoculum before addition to the growth media . However, complete inhibition by these polypeptides was still noted during active growth at turbidities of C . albicans corresponding to 10(6) CFU/ml . At higher cell densities, growth was delayed but not halted under the experimental conditions investigated . Candidacidal activity was observed with both growing and nongrowing cells . With respect to the latter, reaction of cells in buffer with the histidine-rich polypeptides for a period of 30 min resulted in killing of greater than 90% of two different strains of C . albicans, whereas a third strain was found to be less susceptible . Moreover, the kinetics of loss of cell viability correlated with the loss of potassium from the cells . In addition to the histidine-rich polypeptides, hen egg white lysozyme, poly-L-lysine, and poly-L-histidine affected C . albicans . Both of the polyamino acids completely inhibited the growth of the yeast whereas lysozyme was not as potent . Where delays in growth were observed for all of these agents, including the histidine-rich polypeptides, turbidities reached those of untreated controls after a 24-h period . Enhanced effects were noted if C . albicans was preincubated with these agents in 0.025 2-(N-morpholino)-ethanesulfonic acid buffer, pH 5.2, before growth in the yeast synthetic medium. Infect Immun, 1984 Jun, 44(3), 623 - 6 Altered expression of human monocyte Fc receptors in Plasmodium falciparum malaria; Ward KN et al.; The state of activation of human peripheral blood monocytes was examined by using a rosette assay that detects changes in Fc receptor expression . Monocytes from patients with uncomplicated Plasmodium falciparum malaria showed a significant increase in the number of rosettes relative to healthy controls . In addition, the monocytes from these patients were tested for their ability to phagocytose Candida albicans, but this ability did not differ from that of normal individuals . Finally, the monocytes from patients with cerebral malaria were also tested for Fc receptor expression . In contrast to the results from uncomplicated cases, the activity of the monocytes from these patients was no different from that of controls . We concluded that uncomplicated P . falciparum malaria caused an increase in monocyte Fc receptor expression which did not occur in cerebral malaria and that this difference in activation may be important in the pathogenesis of cerebral malaria. Br J Vener Dis, 1984 Jun, 60(3), 175 - 7 Single blind comparison of ketoconazole 200 mg oral tablets and clotrimazole 100 mg vaginal tablets and 1% cream in treating acute vaginal candidosis; Bingham JS; A single blind study of 103 women with vaginal candidosis was undertaken to compare treatment with conventional topical clotrimazole and oral ketoconazole . Both treatment regimens were equally effective in terms of clinical symptoms, negative results on culture for Candida albicans, and relapse rates . As treatment for vaginal candidosis takes several days, patient compliance is important and the success of a treatment regimen may depend on its acceptability to patients . Those in this study who had previously been treated for vaginal candidosis were asked to compare their current and previous treatments . Significantly more (p less than 0.001) of those treated with ketoconazole than those treated with clotrimazole found it more acceptable than previous treatment . This indicated a strong preference for oral treatment, and oral antifungal agents may be the treatment of choice for vaginal candidosis in the future. Infect Immun, 1984 Jun, 44(3), 576 - 80 Critical role of germ tube formation in the pathogenesis of candidal vaginitis; Sobel JD et al.; A variant strain of Candida albicans incapable of hyphal production at 37 degrees C was used to study the role of germ tube formation in the pathogenesis of experimental vaginal candidiasis in rats . No difference was observed in the in vitro adherence at 25 degrees C of blastoconidia of the variant strain to vaginal epithelial cells when compared with the parent wild-type, germ tube-producing strain and multiple clinical isolates of C . albicans . However, after exposure to conditions favoring germ tube production, the adherence of the variant strain to epithelial cells was significantly less than that of germinated strains (P less than 0.01) . In vivo animal studies revealed that the variant strain was less likely to result in vaginal colonization and infection than the wild-type strain and the other clinical isolates . Furthermore, infection, when established, was milder, often transient, and with significantly lower titers of cultured vaginal microorganisms obtained by lavage . Electron microscopic studies confirmed the failure of the variant strain to produce hyphae in vivo . The capacity of C . albicans to produce hyphae appears to be an important but nonessential virulence factor in the pathogenesis of candidal vaginitis. Mycopathologia, 1984 May 30, 86(2), 65 - 70 Apparent extracellular glycoprotein turnover product from Candida albicans; Diedrich DL et al.; Low molecular weight material was isolated from the culture medium of three strains of Candida albicans . This material was produced from exponentially growing cultures and it appeared from chemical analysis to represent the carbohydrate portion of cell surface glycoproteins . The material contained a few residual amino acids which were interpreted to represent the attachment points of carbohydrate to protein and the remanents protease cleavage sites . Some of this material could be generated artificially by treating intact cells with papain. Arch Dis Child, 1984 May, 59(5), 479 - 80 Candida albicans skin abscesses; Hensey OJ et al.; Two neonates who developed Candida albicans skin abscesses are described . One developed disseminated infection . In the newborn abscesses cannot be assumed to be of bacterial origin. J Gen Microbiol, 1984 May, 130 ( Pt 5), 1217 - 25 Isolation and structure of glucan from regenerating spheroplasts of Candida albicans; Gopal P et al.; Regenerating spheroplasts of Candida albicans formed organized glucan nets in liquid culture . The nets consisted of interwoven microfibrils about 50 nm wide, but of an undetermined length . Partial acid hydrolysis of the polysaccharide showed the presence of chains of beta(1----3)- and beta(1----6)-linked glucose residues, but no intrachain beta(1----3) and beta(1----6) linkages . Periodate oxidation and GLC of the methylated glucan indicated a highly branched polymer (9.5% branch points) . Sequential enzymic degradation of the isolated nets confirmed the presence of chains of beta(1----3)- and beta(1----6)-linked glucose residues . Degradation by (1----3)-beta- and (1----6)-beta-glucanase released 23% (w/w) and 30% (w/w) respectively of the carbohydrate as glucose equivalents . The residual material was degraded by chitinase . Equal amounts of N-acetylglucosamine and glucose equivalents were detected in the chitinase hydrolysate, suggesting a possible linkage between glucan and chitin . Our data indicate that the cell wall of C . albicans contains at least two highly branched glucans with predominantly beta(1----3) or beta(1----6) linkages. Zentralbl Bakteriol Mikrobiol Hyg {B}, 1984 May, 179(2), 125 - 9 The choice of fungi as test organisms in disinfectant testing; van de Voorde H et al.; In order to find out whether more than one test organism is needed for the determination of the activity of disinfectants towards mycelium-forming fungi and yeasts, eight different species of fungi and one yeast-like fungus were submitted to seven different disinfectants in varying concentrations . As Candida albicans was found to be the most resistant, the authors propose that only Candida albicans should be used. Clin Allergy, 1984 May, 14(3), 221 - 31 In vitro investigations in asthmatic children undergoing hyposensitization with tyrosine-adsorbed Dermatophagoides pteronyssinus antigen; Turner MW et al.; Successful hyposensitization to Dermatophagoides pteronyssinus in perennial childhood asthma was associated with a slight mean rise of serum IgG antibody to the mite antigen in contrast to a placebo group in whom this antibody fell slightly . No relationship was detected between the effect on asthma and the magnitude of this change . Nor was there any consistent effect on IgE or IgA antibody . There was a wide range of total serum IgE and IgE, IgG and IgA antibody to D . pteronyssinus before treatment; this level did not predict the effect of treatment . Some patients lacked IgA antibody . IgE antibody to timothy grass pollen was raised in some but not others . These levels did not change systematically during the study and improvement occurred in those who had this antibody as well as IgE antibody to D . pteronyssinus . IgG and IgE antibodies to D . pteronyssinus were significantly correlated in the pre-treatment samples . Lymphocyte thymidine uptake was lower after 8 weeks of treatment than in the control group, not only after stimulus with D . pteronyssinus antigen, in vitro, but also with antigen from Candida albicans . This was not a serum effect . The late bronchial provocation response was lost only in those with serum IgA less than the log mean for age. Infect Immun, 1984 May, 44(2), 537 - 9 Heat shock and heat stroke proteins observed during germination of the blastoconidia of Candida albicans; Dabrowa N et al.; Cytoplasmic proteins extracted from germinating yeast cells of Candida albicans were analyzed by sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis . Similar extracts from a recently isolated nongerminating variant were compared with those from the parent . Five proteins (18, 22, 40, 68, and 70 kilodaltons {kd}) behaved as heat-shock proteins in that they appeared or were greatly increased in amount within 20 min of a temperature shift from 23 to 37 degrees C . Three of the five (40, 68, and 70 kd) were undetected in cells incubated at 23 degrees C, appeared within 20 min of temperature shift, and were no longer detected after 120 min at 37 degrees C, whereas two of the five (18 and 22 kd) were present in small amounts at 23 degrees C, increased greatly after shift, and persisted for 120 min at the elevated temperature . Two temperature-repressed (heat-stroke) proteins (30 and 88 kd) were also observed . The same heat-shock and heat-stroke proteins were also found in the nongerminating variant . The differences in proteins expressed by blastoconidia and by germlings appeared to be related to the heat-shock response. Chest, 1984 May, 85(5), 699 - 701 Allergic bronchopulmonary candidiasis; Akiyama K et al.; A patient had an illness consistent with allergic bronchopulmonary candidiasis . She had asthma, fleeting pulmonary infiltrate, immediate skin reactivity and precipitating antibody against Candida albicans, elevated total serum IgE concentration, elevated IgE and IgG antibody activity against C albicans, and two positive sputum cultures for C albicans . Serial serologic studies showed a significant decrease of serum IgE levels and IgE antibody activity after corticosteroid treatment. J Gen Microbiol, 1984 May, 130 ( Pt 5), 1227 - 36 Exo-(1----3)-beta-glucanase, autolysin and trehalase activities during yeast growth and germ-tube formation in Candida albicans; Ram SP et al.; Exo-(1----3)-beta-glucanase, beta-glucosidase, autolysin and trehalase were assayed in situ in Candida albicans during yeast growth, starvation and germ-tube formation . Cell viability, germ-tube formation, intracellular glucose-6-phosphate dehydrogenase and beta-glucosidase were unaffected in cells incubated in 0.1 M-HC1 for 15 min at 4 degrees C . However, in situ trehalase, (1----3)-beta-glucanase and autolysin activities in acid-treated cells decreased by 95, 50 and 35% respectively, indicating that these enzymes are, in part, associated with the cell envelope . Trehalase activity increased throughout yeast growth and remained elevated during the first hour of incubation for germ-tube formation . All of the in situ trehalase activity in starved yeast cells could be measured without the permeabilizing treatment . beta-Glucosidase activity declined throughout yeast growth and did not alter during germ-tube formation . Both the (1----3)-beta-glucanase and autolysin activities were optimal at pH 5 X 6, inhibited by gluconolactone and HgCl2, and maximal at 15-16 h during yeast growth . Although autolysin activity increased by 50-100% when starved yeast cells were incubated for germ-tube formation, the in situ (1----3)-beta-glucanase remained constant . When acid-treated starved yeast cells were similarly induced, in situ (1----3)-beta-glucanase increased 100% over 3 h of germ-tube formation . Yeast cells secreted (1----3)-beta-glucanase into the growth medium . This was highest in early exponential phase cultures (34% of the maximum in situ activity) and declined throughout growth . (1----3)-beta-Glucanase was also secreted into the medium during germ-tube formation and this represented 80-100% of the in situ activity in germ-tube forming cells . Both secretion of (1----3)-beta-glucanase and germ-tube formation were inhibited by 2-deoxyglucose, ethidium bromide, trichodermin and azaserine. Mol Biochem Parasitol, 1984 May, 12(1), 1 - 13 Effects of ketoconazole on growth and sterol biosynthesis of Leishmania mexicana promastigotes in culture; Berman JD et al.; Ketoconazole, a clinically effective antimycotic agent active in vitro against the amastigote stage of Leishmania mexicana Walter Reed 227 in human monocyte-derived macrophages, was found to inhibit growth and impair sterol biosynthesis of the cultured promastigote stage by approx . 50% at a concentration of approx . 10(-8)M . Sterol biosynthesis was interfered with at the level of the removal of the 14 alpha-methyl group of lanosterol, as judged by changes in the distribution of {2-14C}mevalonate radioactivity among desmethyl sterol and methyl sterol thin-layer chromatography fractions, by the loss of 4-desmethyl sterols (mainly 5-dehydroepisterol), and by the accumulation of 14 alpha-methyl sterols . The growth inhibition and sterol changes were evident in promastigotes cultured in a cholesterol-rich medium and in a cholesterol-poor medium, even though promastigotes incorporated cholesterol . The mechanism of action of ketoconazole against promastigotes may be that postulated for Candida albicans: interference with membrane permeability secondary to loss of desmethyl sterols and accumulation of 14 alpha-methyl sterols. Mycopathologia, 1984 Apr 15, 85(3), 129 - 44 Experimental pulmonary candidiasis in modified rabbits . Histopathological, ultrastructural and enzyme cytochemical studies of tissue reactions; Nakamura T; The present experiment was performed in order to analyze and compare the histopathological features of Candida infection in various states of host defense capacity . The pulmonary lesions were induced by an intratracheal inoculation of 10(8) live cells of Candida albicans into each of the rabbits in the following 4 groups: 1) untreated controls, 2) animals sensitized non-specifically to bovine serum albumin (BSA), 3) those sensitized specifically to formalin-killed C . albicans cells, and 4) those treated with cyclophosphamide and mitomycin C . The animals were sacrificed at appropriate intervals up to 16 days after inoculation . At autopsy, the lungs were cultured and then subjected to histopathological, electron microscopic and enzyme cytochemical examinations . In the healthy control animals, the fungal lesions consisted of polymorphonuclear leukocytes (PMN) at the initial stage, gradually changing to granulomatous inflammation, which contained no peroxidase-positive macrophages . In the animals sensitized non-specifically to BSA exudative macrophages appeared in the lesions, the nature of which did not differ from that of the control animals . In the animals sensitized specifically to Candida cells, more extensive infiltration of PMN was observed at the initial stage, a fact which may suggest the participation of the Arthus phenomenon in the development of the lesions . Furthermore, an epithelioid cell transformation of the macrophages in the granulomatous lesions may also suggest that immune complexes contributed to their formation . In the drug-treated animals, the lesions consisted of necrotic or less prominent cellular foci which correspond to the features of human candidiasis in debilitated states, and the inoculated fungi grew progressively to form pseudohyphae . An asteroid structure protruding radially from the surface of the fungal cells and attaching to primary lysosomes in the phagocytes was observed occasionally . This structure seems to be formed when the function of the phagocytes in the defense mechanisms against the fungi is suppressed to some extent . From the results of the present experiment, we would emphasize that PMN play an initial role in the elimination of C . albicans cells in the lung, and that macrophages then contribute to the formation of the lesions immunologically or non-immunologically. Mycopathologia, 1984 Apr 15, 85(3), 171 - 3 Adherence of Candida albicans to buccal epithelial cells of neonates; Davidson S et al.; Adherence of Candida albicans to buccal epithelial cells of newborn infants was studied by the visual adherence method . Forty-five samples of buccal epithelial cells were obtained from 21 normal newborns at different times following delivery . In group 1 (mean age 7.5 hr) 367 +/- 51 yeast cells adhered to 100 epithelial cells . In group 2 (mean age 2.3 days) 384 +/- 36 yeast cells adhered to 100 cells . In group 3 (mean age 6.2 days) 488 +/- 57 yeast cells adhered to 100 cells . Differences among the groups were not significant (p greater than 0.1) . A significant difference was found in the percentage of epithelial cells binding 10 yeast cells between group 1 (7.25 +/- 0.9) and group 3 (14.9 +/- 2.5), and group 2 (8.0 +/- 2.0) and group 3 (p less than or equal to 0.025) . In 12 infants studied twice at mean age of 2.1 and 6.3 days (included in groups 2 and 3) a significant increase was found in the number of adherent yeasts binding to 100 epithelial cells (330 +/- 87 and 485 +/- 52 respectively) (p less than or equal to 0.03), and in the percentage of epithelial cells binding greater than or equal to 10 yeast cells (5.0 +/- 3.0 and 14.7 +/- 3.5 respectively, p less than or equal to 0.004) for each infant . The age-related increased affinity of buccal epithelial cells to Candida albicans may have relevance in the development of oral thrush. Aust Fam Physician, 1984 Apr, 13(4), 292 - 3 Three day treatment of vaginitis with econazole nitrate cream; Rana C et al.; The cure rate of a short term twice daily therapy for vulvovaginal infection caused by Candida albicans is shown to be comparable with the results of longer courses of treatment . Three quarters of patients studied approved of the twice daily therapy. J Antimicrob Chemother, 1984 Apr, 13(4), 377 - 82 The penetration of latamoxef disodium (moxalactam) into the subcutaneous fat and skeletal muscle of ischaemic lower limbs with atherosclerotic disease; Stewart J et al.; After pre-operative administration of 1 g, latamoxef disodium (moxalactam) levels were measured in peripheral venous blood, skeletal muscle and subcutaneous fat sampled from 29 patients during either arterial reconstruction or amputation undertaken for arterial occlusive disease . Tissue samples were taken from both proximal and distal levels in the amputated limbs . Levels of latamoxef disodium were above the minimum inhibitory concentration required for most commonly encountered Gram-positive and Gram-negative organisms . No patients developed toxicity or superficial wound infection but there was one vascular graft infection by Candida albicans . It has been shown that latamoxef disodium penetrates rapidly into the subcutaneous fat and skeletal muscle of relatively ischaemic limbs, achieving levels inhibitory to many common pathogens. J Med Microbiol, 1984 Apr, 17(2), 181 - 7 Host resistance to Candida albicans in uraemia; Miller TE et al.; In renal failure, infection is a frequent complication and cause of death, which suggests that uraemia impairs immunity . In a comparison of Candida albicans fungaemia, peritonitis and subcutaneous infection in normal and severely uraemic rats, uraemia did not affect the course of these infections . C . albicans is an important pathogen in immunocompromised hosts and we conclude that uraemia is unlikely to be the primary factor that increases host susceptibility to infection with this fungus. J Exp Med, 1984 Apr 1, 159(4), 1289 - 94 Functional and biochemical studies of multinucleated giant cells derived from the culture of human monocytes; Schlesinger L et al.; We compared phagocytic and metabolic activities of multinucleated giant cells (MGC) and macrophages derived from human monocytes after 9-14 d in culture . Phagocytosis of sheep erythrocytes (E) coated with IgG, of E coated with IgM and complement, and of Candida albicans was comparable in MGC and macrophages . The same percentage of ingested fungi was killed by MGC (24 +/- 4%) and macrophages (21 +/- 5%) . Approximately 70% of MGC and macrophages exhibited superoxide-dependent reduction of nitroblue tetrazolium during stimulation . Ia antigen was present on approximately 75% of both cell types . Analysis of cell populations separated by nuclear fluorescence indicated that beta-glucosaminidase, acid phosphatase, and beta-glucuronidase activity per cell was higher in MGC, but specific activity of these enzymes was greater in macrophages . These results suggest that MGC have the capacity to function like macrophages in host defense against infection. Pediatr Dermatol, 1984 Apr, 1(4), 322 - 5 Corn starch, Candida albicans, and diaper rash; Leyden JJ; The growth of Candida albicans experimentally inoculated onto the skin of human volunteers was not enhanced by the addition of either cornstarch powder or talcum powder . Sufficient nutrients for growth of C . albicans exist on human skin, provided sufficient moisture is present . Cornstarch and talc powders were shown to minimize frictional injury experimentally induced in human volunteers . These studies indicate that cornstarch and talc powders do not enhance the growth of yeasts on human skin and do provide protection against frictional injury. Antimicrob Agents Chemother, 1984 Apr, 25(4), 483 - 7 Effect of the antimycotic drug naftifine on growth of and sterol biosynthesis in Candida albicans; Ryder NS et al.; Naftifine, a new antimycotic drug of the allylamine class, is a potent inhibitor of ergosterol biosynthesis in Candida albicans . Treated cells showed a dose-dependent drop in ergosterol content; the level was reduced by 60% at concentrations of greater than 50 mg/liter, causing total inhibition of growth . This inhibition coincided with a heavy accumulation of the sterol precursor squalene . Radiolabeling experiments showed that the inhibition of sterol synthesis was complete within 10 min of exposure of cells to the compound . Control cells incorporated {14C}acetate into nonsaponifiable lipids composed primarily of ergosterol, whereas naftifine-treated cells accumulated only labeled squalene . When the drug was removed by washing cells thoroughly in 1% Tween 80, the accumulated squalene was further metabolized to ergosterol . A similar pattern of inhibition was observed in sterol biosynthesis from {14C}mevalonate in a cell-free system . At 50 mg/liter, naftifine gave greater than 99% inhibition of sterol biosynthesis both in whole cells and in cell extracts of C . albicans . The primary action of naftifine appears to be the blocking of fungal squalene epoxidation. Antimicrob Agents Chemother, 1984 Apr, 25(4), 450 - 4 Inhibition and killing of Candida albicans in vitro by five imidazoles in clinical use; Lefler E et al.; Five imidazoles (clotrimazole, econazole, ketoconazole, miconazole, and tioconazole) in clinical use were compared for their ability to inhibit and kill Candida albicans . Eleven isolates were obtained from patients before therapy . By spectrophotometric determination of 50% growth inhibition, all isolates were inhibited at low concentrations, with clotrimazole slightly less active than the other four drugs . By the conventional MIC determination, tioconazole was more active than all of the others (P less than 0.01) except clotrimazole . In killing (minimum fungicidal concentration {MFC} assay), tioconazole was the most active by several analyses . Studies of the kinetics of killing indicated that the drugs studied could kill under conditions used for the MFC determination and that tioconazole and ketoconazole could kill particularly rapidly . If the drug was washed from the cells before subculturing, concentrations above the MFC were required to kill, but tioconazole could produce a lethal lesion in all cells virtually instantaneously . These findings are pertinent to MFC and killing kinetics methodology and to the observation of drug persistence after topical application . The results differ from some previous in vitro comparisons made with different methods . They are relevant to conclusions about drug mechanisms based on their abilities to inhibit and to kill, and they underscore the need to study various assay methods and fungal species. Biull Eksp Biol Med, 1984 Apr, 97(4), 460 - 2 {Structural and functional study of acidification in the process of phagocytosis}; Khramtsov AV et al.; Morphometry and cytofluorometry of the kinetics of phagocytosis were applied to study the quantitative mechanisms of acidification in the area of contact between the plasma membrane of macrophages and Candida albicans yeast cells conjugated with fluorescein isothiocyanate . It was found by stereological transformation of the morphometry data that the main part of macrophages phagocytose the limiting amount of particles by minute 5-10 . A good agreement was established between the cytofluorometric histograms and the stereological data . This made it possible to evaluate, using the calibration curve, the pH on the surface of the phagocytosed material based on the fluorescence quenching . As an advantage of the suggested comprehensive approach to the study of acidification, the authors stress the possibility of making structural-functional analysis of the rearrangements occurring in the intact phagocytosing cell. Appl Environ Microbiol, 1984 Apr, 47(4), 647 - 52 Colonization of congenitally athymic, gnotobiotic mice by Candida albicans; Balish E et al.; Colony counts, scanning electron microscopy, and light microscopy were used to assess the capacity of Candida albicans to colonize (naturally) and infect the alimentary tract of adult and neonatal (athymic {nu/nu} or heterozygous {+/nu} littermates) germfree BALB/c mice . When exposed to yeast-phase C . albicans, the alimentary tract of adult germfree mice (nu/nu or +/nu) is quickly (within 24 to 48 h) colonized with yeast cells . Neither morbidity nor mortality was evident in any mice that were colonized with a pure culture of C . albicans for 6 months . Yeast cells of C . albicans predominated on mucosal surfaces in the oral cavities and vaginas of adult athymic and heterozygous mice . In both genotypes, C . albicans hyphae were observed in keratinized tissue on the dorsal posterior tongue surface and in the cardial-atrium section of the stomach . Conversely, neonatal athymic or heterozygous mice, born to germfree or C . albicans-colonized mothers, do not become heavily colonized or infected with C . albicans until 11 to 15 days after birth . Although yeast cells adhered to some mucosal surfaces in vivo, neither widespread mucocutaneous candidiasis, i.e., invasion of mucosal surfaces with C . albicans hyphae, nor overwhelming systemic candidiasis was evident in neonatal (nu/nu or +/nu) mice . Thus, even in the absence of functional T-cells and a viable bacterial flora, athymic and heterozygous littermate mice (adult or neonatal BALB/c) that are colonized with a pure culture of C . albicans manifest resistance to extensive mucocutaneous and systemic candidiasis. J Med Microbiol, 1984 Apr, 17(2), 211 - 3 Antimicrobial effects of a macrophage-derived cytotoxin from the serum of BCG-primed rabbits (tumour necrosis serum); Neale ML et al.; Previous studies have shown that a macrophage-derived cytotoxin, found in high titre in the serum of BCG-primed rabbits, killed malarial parasites and certain tumour cells . In this study, the macrophage cytotoxin was tested for activity against microorganisms other than protozoa . No activity was seen against a range of gram-negative or gram-positive bacteria or against Candida albicans . It is concluded that the macrophage cytotoxin has limited anti-microbial activity, perhaps restricted to certain intra-cellular parasites. J Pharm Pharmacol, 1984 Apr, 36(4), 283 - 4 In-vitro evaluation of the anticandidiasis activity of honey distillate (HY-1) compared with that of some antimycotic agents; Obaseiki-Ebor EE et al.; The susceptibility of 72 isolates of Candida albicans to the antimicrobial honey distillate fraction (HY-1) and several antimycotic agents is presented . All the isolates were sensitive to HY-1, H-115 and Jadit, while about 10% of the isolates were variably resistant to nystatin, miconazole nitrate and clotrimazole . The nystatin, miconazole nitrate and clotrimazole resistant isolates were inhibited by HY-1. Biochem Biophys Res Commun, 1984 Mar 30, 119(3), 962 - 7 Glyoxalase-I activity and cell cycle regulation in yeast; Dudani AK et al.; The status of glyoxalase-I was explored in exponentially growing and G1 arrested temperature sensitive (ts) cell division cycle (cdc) mutants of Saccharomyces cerevisiae . It was observed that the specific activity of this enzyme was correlated with overall growth status . The activity was high in actively growing cells and was low in G1 arrested cells . Specific activities of glyoxalase-I were also low in G1 arrested prolonged stationary phase (PSP) cells of S . cerevisiae and Candida albicans . The activity of glyoxalase-I recovered when G1 arrested S . cerevisiae (ts) cells were allowed to regrow under permissive conditions . Results demonstrate that although glyoxalase-I activity is a good indicator of cell growth status, it is not involved in cell cycle regulation of this eukaryotic organism. Mycopathologia, 1984 Mar 15, 85(1-2), 21 - 30 A characterization of pH-regulated dimorphism in Candida albicans; Buffo J et al.; When cells of the dimorphic yeast Candida albicans are grown to stationary phase in defined liquid medium at 25 degrees C, they accumulate as singlets in G1 of the cell cycle . When these pluripotent, stationary phase singlets are released into fresh medium at 37 degrees C, they synchronously evaginate after an average period of 135 to 140 minutes and form either buds or mycelia, depending upon the pH of the medium into which they are released . This method of dimorphic regulation offers the distinct advantage of comparability and serves as a very precise method for temporal comparisons of molecular and cytological events related to the establishment of the alternate growth phenotypes . In the present report, we have carefully examined the effects of individually varying pH or temperature on the length of the pre-evagination period, the population synchrony for evagination, and the phenotype of daughter cells . Exact phenotypic transition points, optima, and upper limits are defined for both temperature and pH . In addition, a method of pH-regulated dimorphism is developed in which the original temperature shift is removed from the inductive process . Finally, a common transition phenotype is described for cells reverting from the initial mycelial to budding phenotype when either pH or temperature traverse their respective transition points . The advantages as well as limitations of pH-regulated dimorphism are discussed in detail. J Chromatogr, 1984 Mar 9, 306, 117 - 24 Purification of soluble specific antigens of systemic candidiasis by antibody affinity chromatography; Benbouzid A et al.; Serological methods can be applied to the diagnosis of systemic candidiasis, but cell wall mannans can detect antibodies occurring in several cases unrelated to candidiasis . The present study proposes a procedure for the preparation of specific antigens obtained from an experimental infectious model . The specific immunoglobulins were obtained from rabbits with chronic systemic candidiasis . After precipitation by ammonium sulfate and purification by ion-exchange chromatography on DEAE-Sephadex A-50, these immunoglobulins were fixed on cyanogen bromide-activated Sepharose 4B and used for the preparation of an affinity chromatography column . This column allowed isolation of specifically bound fractions of Candida albicans soluble antigens . When analyzed by quantitative immunoelectrophoresis with a polyvalent hyperimmune antiserum, these fractions showed eight precipitation lines, whereas the complete soluble antigen exhibited 48 lines . Possible applications of these antigens to specific serodiagnosis of systemic candidiasis are being evaluated. Antimicrob Agents Chemother, 1984 Mar, 25(3), 366 - 7 Prophylaxis of Candida albicans infection in neutropenic mice with liposome-encapsulated amphotericin B; Lopez-Berestein G et al.; The efficacy of liposome-encapsulated amphotericin B in the prophylaxis of disseminated Candida albicans infections in neutropenic mice was studied . The administration of liposome-encapsulated amphotericin B was associated with protection against infection with C . albicans when used at doses of greater than or equal to 2 mg of amphotericin B per kg of body weight . Neither empty liposomes nor free amphotericin B showed prophylactic efficacy. Clin Pediatr (Phila), 1984 Mar, 23(3), 179 - 81 Esophagitis associated with Candida infection in a neonate; Petru A et al.; A 14-day old infant with stomatitis due to Candida albicans presented with frequent emesis and was found to have esophagitis by barium esophagram . She responded promptly to oral Mycostatin suspension: her emesis subsided and the stomatitis resolved . Repeat esophagram on the seventh day of therapy showed complete resolution of the esophageal mucosal abnormalities . Although Candida stomatitis is common in infants, the incidence and appropriate therapy of Candida esophagitis as a complication in otherwise normal infants are unknown . This patient responded well to frequent therapy with an oral, nonabsorbable antifungal agent. Clin Rheumatol, 1984 Mar, 3 Suppl 1, 25 - 32 Changes in mononuclear cell function in patients with rheumatoid arthritis following treatment with auranofin; Coughlan RJ et al.; Gold salts in vitro modulate lymphocyte proliferation to mitogens and antigens and macrophage phagocytosis . These effects are not confined to gold salts; D-penicillamine and chloroquine as well as some of the non-steroidal anti-inflammatory drugs (NSAIDs) have in vivo immunoregulatory effects . Peripheral blood mononuclear cells during treatment with Myocrisin (gold sodium thiomalate, GSTM) show changes that differ from in vitro effects and are related to therapeutic response rather than GSTM administration . This discrepancy between in vitro and ex vivo responses prompted us to measure cellular functions during auranofin therapy . Twenty-nine patients with rheumatoid arthritis took part in a placebo-controlled trial of auranofin . We examined the spontaneous immunoglobulin (IgG and IgM) and IgM rheumatoid factor (IgM RF) production by cultured mononuclear cells, lymphocyte transformation to concanavalin A and macrophage phagocytosis of Candida albicans . There was a significant fall in IgG synthesis (p less than 0.005) and IgM RF synthesis (p less than 0.005) over the first 4 months of treatment, whereas in the control group there were no significant changes . There was no significant change in IgM production . In the auranofin-treated group the lymphocyte response to concanavalin A fell progressively during 6 months of therapy (at 2 months p less than 0.05, at 4 months p less than 0.01, and at 6 months p less than 0.005) . Auranofin therapy had variable effects on monocyte phagocytosis of C . albicans . Therefore, in contrast to GSTM, auranofin suppressed both in vitro and ex vivo lymphocyte functions . This effect is probably related to the direct effect of auranofin on lymphocyte membranes. Antibiotiki, 1984 Mar, 29(3), 198 - 201 {Combined action of amphotericin B and methacyclin on Candida albicans}; Araviiskii RA et al.; The combined effect of amphotericin B, a polyene antibiotic, and metacycline, a tetracycline antibiotic, on the cells of C . albicans was studied . The method of square titration followed by quantitative plating of the samples was used for estimation of the combination efficiency . An attempt was also made to investigate the characteristic features of metacycline penetration into the yeast cells under the effect of various doses of the polyene antibiotic . The capacity of metacycline for fluorescence in the yellow-green pectral region was employed for this purpose . It was shown that the drugs had a synergistic effect on C . albicans . The fluorescence research methods allowed one to demonstrate that even low subinhibitory doses of amphotericin B increased the permeability level of the cytoplasmic membrane and provided penetration of metacycline into the cytoplasm almost during the first hours of the contact . The time course of metacycline cumulation in the cells was followed up and the characteristic features of the antibiotic localization were analysed. Antimicrob Agents Chemother, 1984 Mar, 25(3), 387 - 9 In vitro antifungal activities of amphotericin B and liposome-encapsulated amphotericin B; Hopfer RL et al.; The in vitro activities of liposome-encapsulated amphotericin B and free amphotericin B against Candida albicans 336 were comparable . Amphotericin B concentrations 12-fold and greater than 50-fold higher were required to kill the same organism when cholesterol and ergosterol were incorporated into the liposomes . The addition of cholesterol to liposomes caused a significant increase in the minimal fungicidal concentration of amphotericin B in 7 of 19 other yeast strains tested, whereas ergosterol caused an increase in 18 of the 19 strains. Pathol Biol (Paris), 1984 Mar, 32(3), 160 - 4 {Morphogenesis of Candida albicans in human serum . Mycelial and pseudomycelial tubes observed in 250 strains}; Saez H et al.; The morphogenesis of Candida albicans, more peculiarly the mycelial and pseudomycelial tubes production, was investigated during 24 hours in human serum: on 250 strains at 37 degrees C, and on 24 strains at 25 degrees C . The characteristic of the tubes, their first apparition and maximum production time are reported . The yeast influence (origin, saprophytic or parasitic state, serotype, maximum temperature for growth of the strain) on the tubes production is discussed. South Med J, 1984 Mar, 77(3), 404 - 5 Candida albicans meningitis in a parenteral drug abuser; Kantor HL et al.; We have described a patient with meningitis due to Candida albicans, in whom the only identifiable risk factor was a history of intravenous amphetamine abuse . Despite intravenous therapy with 2 gm of amphotericin B and concurrent 5-fluorocytosine, symptoms, CSF pleocytosis, and hypoglycorrhachia persisted . After a brief course of intrathecal amphotericin B therapy, the patient improved clinically and the CSF returned to normal. J Dent Res, 1984 Mar, 63(3), 435 - 40 The control of morphogenesis in Candida albicans; Shepherd MG et al.; Morphogenesis (germ-tube formation) in Candida albicans was induced gratuitously by N-acetylhexosamine derivatives (N-acetyl-glucosamine covalently linked to agarose, N-acetylmannosamine, hyaluronic acid, colloidal chitin, and mucin) . These compounds were not taken up by the yeast cells and did not support growth . 2-Deoxyglucose was a potent inhibitor of germ-tube formation (50 microM), but did not affect the yeast growth yield at a concentration of 2.5 mM . 2-Deoxyglucose covalently linked to agarose did not affect germ-tube formation, and the inhibition by free 2-deoxyglucose was overcome by the addition of glucose to the germ-tube-forming cells . Glucose competitively inhibited 2-deoxyglucose uptake (Ki = 0.14 mM), and these data indicate that 2-deoxyglucose acted intracellularly. Infect Immun, 1984 Mar, 43(3), 1012 - 8 Production and characterization of three monoclonal antibodies to Candida albicans proteins; Strockbine NA et al.; Three monoclonal antibodies, designated A2C7, C2C7, and F19, were produced which recognize proteins from Candida albicans . All are of the immunoglobulin G1 heavy chain and kappa light chain class . A2C7 and C2C7 immunoprecipitated three proteins contained in a partially purified fraction (region A) of a mycelial cytoplasmic extract of C . albicans . The apparent molecular weights of these proteins are 120,000 (120K) to 135K, 44K to 52K, to 38K . Monoclonal antibody F19 was reactive with proteins of 42K, 43K, and 50K in immunoblotting experiments . F19 was also able to form a precipitin band in agarose gel with protein(s) contained in region A . Limited proteolytic digestion of the three proteins immunoprecipitated by A2C7 and C2C7 demonstrated that both monoclonal antibodies recognized the same three Candida proteins and that there exists a significant degree of relatedness in primary structure among the three proteins . Proteins with apparent molecular weights of 120K to 135K, 44K to 52K, and 35K to 38K that were immunoprecipitated by sera from two patients with invasive candidiasis and by the serum from a rabbit immunized against a 48K (44K to 52K) Candida protein were also analyzed by limited proteolysis . Patterns of peptide fragments generated by enzymatic digestion of these proteins showed that the proteins recognized by the monoclonal antibodies are the same proteins recognized by antibodies in the sera of patients during an invasive Candida infection and by antibodies in the serum of the immune rabbit. J Gen Microbiol, 1984 Mar, 130 ( Pt 3), 465 - 71 Interactions of Candida albicans yeast cells, germ tubes and hyphae with human polymorphonuclear leucocytes in vitro; Cockayne A et al.; Suspensions of Candida albicans yeast cells, germ tubes and hyphae with biomass standardized by ATP measurement were compared for their relative susceptibilities to phagocytosis and intracellular killing by human polymorphonuclear leucocytes . All three forms were ingested to a similar extent, but significantly fewer yeast cells were killed intracellularly after ingestion than were filamentous forms of the fungus . Ketoconazole pretreatment significantly enhanced the susceptibility of hyphae, but not of germ tubes, to phagocytosis and intracellular killing . The opsonic requirements of the yeasts and filamentous forms for efficient phagocytosis and killing differed. Antimicrob Agents Chemother, 1984 Mar, 25(3), 316 - 8 Growth phase in relation to ketoconazole and miconazole susceptibilities of Candida albicans; Beggs WH; The antifungal imidazoles miconazole and ketoconazole inhibit synthesis of essential cell membrane components . Furthermore, miconazole can exert direct physicochemical cell membrane damage at relatively high levels, but ketoconazole cannot . Experiments were designed to explain our previous observation that concentrations of miconazole capable of causing direct membrane damage were no more active against Candida albicans than equimolar levels of ketoconazole . When stationary-phase cells were inoculated into medium containing either drug at 3.8 X 10(-5) M, fungistatic effects were indistinguishable . If, however, such cultures were incubated 3 h before drug addition, differences were remarkable . After 3 h, miconazole caused a 99% reduction in CFU per milliliter within 20 min, but ketoconazole again was only fungistatic . The immediate onset, rapidity, and magnitude of the miconazole effect were indicative of direct lethal cell damage . Miconazole concentrations as low as 1.0 X 10(-5) M were similarly active . It was concluded that C . albicans undergoes phenotypic changes during the growth cycle that coincidentally confer susceptibility or resistance to the lethal direct membrane damage effect of miconazole . The fungistatic or metabolic effects of ketoconazole or low-level miconazole appeared to be independent of growth phase. J Trauma, 1984 Mar, 24(3), 220 - 3 Kinetics of peripheral blood T cell numbers and functions in patients with burns; Menon T et al.; Cell-mediated immunity (CMI) was assessed in 58 patients with burns involving 10% to 40% of the total body surface area (TBSA), and in 16 normal healthy individuals, by using two parameters, the total T-cell counts in peripheral circulation and T-cell function as indicated by the leukocyte migration inhibition (LMI) test . Three recall antigens from Candida albicans, S . typhi, and E . histolytica were used to elicit the LMI . T-cell function was found to be significantly depressed in burns involving more than 25% TBSA . Depression of T-cell function started after the seventh postburn (PB) day and continued until the sixtieth PB day. J Bacteriol, 1984 Mar, 157(3), 918 - 24 Repetitive DNA of Candida albicans: nuclear and mitochondrial components; Wills JW et al.; We report the isolation and analysis of the rapidly reassociating DNA of the pathogenic, dimorphic fungus Candida albicans . Minicot analysis of whole-cell repetitive DNA suggested that a significant portion of this component was mitochondrial DNA . Genomic blot hybridizations in which radioactive whole-cell repetitive DNA was used as a probe revealed eight major EcoRI bands in the molecular weight range resolved by the gel system used . Isolation and analysis of high-purity mitochondrial DNA have shown that five of these bands are of mitochondrial origin . The remaining three bands are of nuclear origin and represent repetitive sequences that are found in the nuclear genome . Attempts to isolate nuclear DNA that was completely free of mitochondrial DNA contamination were unsuccessful. Infect Immun, 1984 Mar, 43(3), 1100 - 2 Killing of Aspergillus fumigatus spores and Candida albicans yeast phase by the iron-hydrogen peroxide-iodide cytotoxic system: comparison with the myeloperoxidase-hydrogen peroxide-halide system; Levitz SM et al.; A new fungicidal system composed of ferrous ion, H2O2, and iodide is described and compared with the myeloperoxidase-hydrogen peroxide-halide system . Both systems had similar activity against Aspergillus fumigatus spores and the Candida albicans yeast phase, but only the ferrous ion-hydrogen peroxide-iodide system was inhibited by hydroxyl radical scavengers. Infect Immun, 1984 Mar, 43(3), 850 - 5 Characterization of antigens specific to the surface of germ tubes of Candida albicans by immunofluorescence; Sundstrom PM et al.; To characterize germ tube-specific antigens of Candida albicans, rabbit antiserum prepared to Formalin-treated yeast possessing germ tubes was adsorbed with stationary-phase blastospores . By immunofluorescence and enzyme-linked immunosorbent assay, this antibody did not react with blastospores but detected germ tube-specific antigens in hyphal forms . Germ tube-specific antigens appeared 30 min after placing blastospores in appropriate conditions for germ tube formation . Hyphae, formed by allowing yeast to germinate for 24 h, still retained germ tube-specific antigens, but blastospores budding off these hyphae were unstained, as were log-phase blastospores . Germ tube-specific antigens were sensitive to heat, sodium metaperiodate oxidation, dithiothreitol reduction, and proteolysis with pronase, trypsin, or chymotrypsin, whereas antigens common to blastospores and germ tubes were stable to boiling, treatment with proteolytic enzymes, and dithiothreitol reduction . Thus, surfaces of germ tubes can be distinguished from those of blastospores not only immunologically, but also by the sensitivity of germ tube-specific antigens to proteolytic treatments. Mycopathologia, 1984 Feb 15, 84(2-3), 107 - 13 Studies on defense mechanisms against Candida albicans infection in congenitally athymic nude (nu/nu) mice; Tabeta H et al.; The defense mechanisms against Candida albicans infection were studied by using a mouse thigh lesion model in congenitally athymic nude (nu/nu) mice and their normal littermates (nu/+) . Nu/nu mice were more resistant to C . albicans infection than nu/+ mice judging from the course of the thigh lesion, the results of CFUs (colony-forming units) of C . albicans in the lesion, and histopathological observations . Histopathological and serological studies revealed that granulocytic cellular infiltration was predominant, and there were few indications of development of cell-mediated immunity to protect Candida infection in Candida-infected nu/nu and nu/+ mice . These results confirmed that lower susceptibility of nu/nu mice to C . albicans infection as compared to nu/+ mice was due to accelerated non-specific defense mechanisms in nu/nu mice, and that cell-mediated or humoral immunity played a minor role in the defense against Candida infection in this experimental model . Furthermore, treatment with high titer of rabbit anti-C . albicans serum was effective to control the number of Candida cells in thigh lesions of BALB/c mice . Above experimental results seem to clearly indicate the great variability of defense manifestation according to the experimental model exployed. Mycopathologia, 1984 Feb 15, 84(2-3), 73 - 6 Primary mycotic infection of paranasal sinuses; Surya Prakash Rao G et al.; Eight cases of primary mycotic infection of paranasal sinuses with Aspergillus and Candida species encountered during July, 1979 to December 1981 are being presented . Their clinical, mycological and serological responses have been discussed . Aspergillus flavus was isolated from all the seven cases with aspergillosis and Candida albicans, along with C . tropicalis, was isolated from one case. Mycopathologia, 1984 Feb 15, 84(2-3), 103 - 6 Release of lysosomal enzymes in Candida albicans phagocytosis by rat peritoneal macrophages; Fontenla de Petrino SE et al.; The present paper reports the in vitro release of lysosomal enzymes in the supernatant of cultures of rat peritoneal macrophages, with the addition of Candida albicans cells . Macrophages were taken from the rat peritoneal cavity 72 hr after non-specific activation with Brain-Heart-Infusion (B.H.I.) broth containing 10% proteose-peptone No . 3 . They were then cultured in Parker medium No . 199 (TC 199) . After 24 hr a suspension of Candida albicans cells, in a determined concentration, was added to the peritoneal macrophage cultures . At that time, and during pre-determined periods, the following enzymes in the culture supernatants were studied using colorimetric methods: beta-glucuronidase, beta-galactosidase and acid phosphatase . It is concluded that, under identical conditions, the release of beta-galactosidase and acid phosphatase is higher than for beta-glucuronidase . The release rate of all three enzymes is the highest at a 6 hr incubation period, after which, a gradual decrease leads to the rate down to 50% at 24 hr. Mycopathologia, 1984 Feb 15, 84(2-3), 141 - 9 Demonstration of the polysaccharides in the cell wall of Candida albicans blastospores, using silver methenamine staining and a sequence of extraction procedures; Evron R et al.; Blastospores of Candida albicans were subjected to a series of extractions of increasing severity to remove polysaccharides from the wall . The procedure was observed by electron microscopy, using silver methenamine staining to localize the polysaccharides. J Immunol Methods, 1984 Feb 10, 66(2), 219 - 26 A novel antibody overlay technique for two-dimensional immunoelectrophoresis; Lebecq JC et al.; A new antibody overlay technique for 2-dimensional immunoelectrophoresis (2-D-IEP) is described . After the first dimension electrophoresis of the antigen, the desired amount of antiserum is applied to the initial agarose layer and then evenly distributed over a defined surface of the gel with a PVC film . This modification of the conventional 2-D-IEP procedure makes it possible to perform tandem 2-D-IEPs comparing 2 antisera on the same gel plate, rocket IEPs where several antisera are compared by electrophoresis on the same gel plate, and 2-D-IEPs with an intermediate antiserum, avoiding the need to pour an intermediate gel . With this technique, 77 antigens have been demonstrated in a Candida albicans serotype A somatic antigen preparation . This is the first description of such a large number of immunoprecipitates on the same immunoplate. Am J Dis Child, 1984 Feb, 138(2), 192 - 6 A monocyte disorder in siblings with chronic candidiasis . A combined abnormality of monocyte mobility and phagocytosis-killing ability; Yamazaki M et al.; Immunologic studies were performed on siblings (a 9-year-old boy and an 11-year-old girl) with chronic candidiasis since infancy and showed defective monocyte functions . In vivo migration and in vitro mobility of the monocytes were impaired . In addition, they had defective phagocytosis-killing ability against Candida albicans . There was no factor(s) to inhibit the monocyte functions in the patients' serum, and their mononuclear cells (75% to 80% lymphocytes) did not secrete such an inhibitory factor(s) in vitro . The serum IgG, IgA, IgM, and C3 levels were normal . Delayed hypersensitivity responses to five antigens, including Candida antigen, were absent in the two patients . In vitro T-lymphocyte functions, such as Candida antigen- or mitogen-induced blastogenesis and lymphokine (leukocyte migration inhibitory factor and leukocyte-derived chemotactic factor) production, were normal . The clinical features of our patients were similar to those with chronic mucocutaneous candidiasis (CMC); however, their primary immunologic defect was, unlike that of CMC, in monocytes, but not in T lymphocytes . These results demonstrated a monocyte disorder with defective mobility and phagocytosis-killing ability that contributed to chronic candidiasis. Klin Monatsbl Augenheilkd, 1984 Feb, 184(2), 104 - 8 {Candida albicans endophthalmitis . Results of pars plana vitrectomy without intraocular antimycotic therapy}; Kroll P et al.; An early pars plana vitrectomy was performed without any additional intravitreal antimycotic therapy in 8 eyes of 5 patients with candida endophthalmitis; anatomic healing with a good functional result was obtained . The good prognosis of vitrectomy without intravitreal antimycotic therapy in our patients is seen in (1) a total surgical extraction of the abscess and (2) the better intraocular ventilation obtained for endogenous resistance. J Gen Microbiol, 1984 Feb, 130 ( Pt 2), 325 - 35 Metabolism of {14C}glucose by regenerating spheroplasts of Candida albicans; Gopal P et al.; Spheroplasts of Candida albicans were regenerated in {14C}glucose and buffered magnesium sulphate (0.1 M-Tris/HCl; 0.5 M-MgSO4, pH 7.2) at 35 degrees C . Uptake of glucose by spheroplasts was faster than that by intact yeast cells . After 6 h, 65% of the glucose taken up by the yeast appeared as CO2 and 30% was incorporated into the cellular material . With spheroplasts, 55% of the glucose taken up was expired as CO2, 25% was excreted into the medium as other metabolites and 20% was incorporated into the cells . The regenerating spheroplasts excreted 14C-labelled carbohydrates into the medium which were fractionated on a Sephadex G-15 column . Acid hydrolysis of the low molecular-weight fraction yielded the following sugars: mannose (75.7%), fucose (3.8%), arabinose (3%), galactose (2.1%) and an unidentified monosaccharide (14%) . Spheroplasts did not incorporate mannoprotein into the regenerated wall . The wall carbohydrate from regenerated spheroplasts was fractionated on the basis of solubility in sodium hydroxide . The alkali-insoluble fraction was analysed by sequential enzyme hydrolysis; 40% of the incorporated counts were associated with beta (1----3)-linked glucan and 50% with a mixed glucan comprising beta (1----3)- and beta (1----6)-linkages and chitin. Pathol Biol (Paris), 1984 Feb, 32(2), 80 - 4 {Gonococcal infections in Gabon (Haut-Ogooué)}; Yvert F et al.; The isolation of N . gonorrhoeae in the region of Franceville was attempted on the one hand with 261 men and 261 women presenting urethral or cervical discharge, and on the other hand with 530 women attending a prenatal clinic of whom 42 had cervical discharge while 488 did not . Amongst the men, 69.7% of the urethritis cases were due to N . gonorrhoeae while this bacteria could be isolated from 15.3% of the women with cervical exudates . N . gonorrhoeae could be also identified in 5.5% of the pregnant women of whom 79% were without exudate . The frequency of N . gonorrhoeae isolates from STD consultations was 440 cases per year per 100,000 while the male: female ratio was 4.6 . The isolation rate from pregnant women would indicate however a frequency in women in excess of 1 500 cases per 100,000 . The isolation of N . gonorrhoeae was tabulated according to the age of the patients . The 15-20 year group was clearly the most frequently infected . Trichomonas was observed in 2% of the men and 23% of the women with discharges . Yeasts (chiefly Candida albicans) were found in 23.5% of the women but in none of the men. J Trauma, 1984 Feb, 24(2), 106 - 15 Relative roles of burn injury, wound colonization, and wound infection in induction of alterations of complement function in a guinea pig model of burn injury; Bjornson AB et al.; Stimuli involved in induction of alterations of the complement system and production of circulating inhibitor(s) of phagocytic function of polymorphonuclear neutrophils following burn injury were investigated using a guinea pig model of scald burn injury . The activity of C1-C9, assessed by measurement of total hemolytic complement, was found to increase primarily in response to burn injury per se, whereas reduction in the activity of the alternative complement pathway was shown to develop in association with natural colonization and local burn wound infection with bacterial pathogens . Invasive burn wound infection induced experimentally with Staphylococcus aureus, Pseudomonas aeruginosa, or Candida albicans exacerbated this latter abnormality, caused consumption of C1-C9 activity, and was associated with appearance of serum factors that depressed phagocytosis of Escherichia coli 075 by peritoneal polymorphonuclear neutrophils . Thus injury and coexistent infection both play important roles in induction of humoral alterations of host defense associated with burn injury. Can J Microbiol, 1984 Feb, 30(2), 221 - 7 In vitro binding of Candida albicans yeast cells to human fibronectin; Skerl KG et al.; The binding of Candida albicans yeast cells to human fibronectin (Fn), a major glycoprotein of mammalian cells, was studied using an in vitro assay . Adherence was quantitated in microtiter dishes coated with Fn to which radiolabeled yeast cells were added . Under optimum conditions of the assay, i.e., 1 mM CaCl2 and 70 micrograms Fn protein, approximately 40% of the radiolabeled yeast cells adhered to the Fn . Adherence to Fn was greater at 30 degrees C than at 4 degrees C and was greater with viable yeast cells than with heat-killed cells . Candida albicans (two strains) and C . tropicalis adhered to Fn to a greater extent than C . pseudotropicalis, C . krusei, or Saccharomyces cerevisiae . Pretreatment of C . albicans with chymotrypsin, pronase, or papain, but not pepsin, decreased adherence to Fn . Blocking experiments using mannan, sugars, or amino sugars were carried out by preabsorbing the Fn with each of the above-mentioned compounds . Candida mannan blocked adherence of C . albicans to Fn . The mannan effect was dose dependent . However, adherence of C . albicans to Fn was not significantly reduced by mannose, glucose, or several other sugars . The role of FN as a receptor for the binding of C . albicans yeast cells to buccal and vaginal epithelial cells was investigated also using an in vitro assay . We determined, using indirect fluorescent antibody techniques, that both buccal and vaginal epithelial cells possessed Fn . In addition, yeast cells, when pretreated with Fn, showed reduced adherence with buccal and vaginal cells when compared with nontreated cells . These studies may indicate a role for Fn in the adherence of C . albicans to buccal and vaginal epithelial cells. Can J Microbiol, 1984 Feb, 30(2), 192 - 203 The relationship between yeast cell size and cell division in Candida albicans; Chaffin WL; The mean size and percentage of budded and unbudded cells of Candida albicans grown in batch culture over a wide range of doubling times have been measured . Cell volume decreased with increased doubling time and a nonlinear approach to an asymptotic minimum was observed . When cells were separated by age according to bud scars, each age showed a similar decrease . During each cell division cycle, size increased slowly during both budded and unbudded periods so that each generation was significantly larger than the preceding . There was no difference in size between the parent portion of budded cells and unbudded cells of the same age . Time-lapse photomicroscopy of cells growing on solid medium showed that cells divide asymmetrically with larger parents having a shorter subsequent cycle time than the smaller daughter, although the time utilized for bud formation was similar . When cells were shifted from a medium supporting a low growth rate and small size to a medium supporting a faster growth rate and larger size, both budded and unbudded cells increased significantly in size . As the doubling time increased, both the budded and unbudded portions of parental and daughter cycles increased. Acta Pathol Microbiol Immunol Scand {C}, 1984 Feb, 92(1), 5 - 10 Human blood monocyte function in relation to age; Nielsen H et al.; The human blood monocyte function in relation to age has been studied in 60 healthy persons (age range 24-94 years) . No differences between females and males were seen . The number of phagocytized Candida albicans per monocyte decreased with ageing (greater than 70 years) . Peripheral blood monocyte count, pinocytosis, phagocytosis of latex beads, chemotactic responsiveness and intracellular killing of Candida albicans were independent of age. J Med Microbiol, 1984 Feb, 17(1), 13 - 22 The proteolytic potential of Candida albicans in human saliva supplemented with glucose; Samaranayake LP et al.; The production of proteases by Candida albicans in batch cultures of human saliva supplemented with glucose was investigated with two clinical strains of Candida and both individual and pooled samples of whole saliva from volunteers . Salivary proteolysis during a 48-h period was estimated by biochemical and isoelectric focusing techniques . Candidal growth in saliva was associated with acid production and salivary proteolysis and there was a highly significant positive correlation between these two activities . Neither candidal growth nor proteolysis was observed in glucose-free control samples and with one strain of Candida cultured in the saliva of one individual . Isotachophoretic analysis of culture liquor showed a significant increase in acetate and pyruvate ions . The oral cavity provides niches that have a low pH and are periodically supplemented with dietary carbohydrates . The acidic proteases of C . albicans may play a role in the pathogenesis of oral candidoses. Infect Immun, 1984 Feb, 43(2), 715 - 21 Identification and molecular weight characterization of antigens from Candida albicans that are recognized by human sera; Strockbine NA et al.; Antigenic components in the cytoplasmic extract of Candida albicans were examined after fractionation by concanavalin A-Sepharose and DEAE-Sephacel ion-exchange chromatography . Fractions from the DEAE column were tested by fused rocket immunoelectrophoresis for their reactivity with antibodies in the sera of 20 patients with disseminated candidiasis . Three groups of fractions (regions A, B, and C) from the DEAE column were defined by their reactivity with these sera . Immunoblot analysis with 20 human sera identified 18 antigenic components in regions A, B, and C . Region A contained nine antigens, region B contained four antigens, and region C contained five antigens . Region A contained an antigen with an apparent molecular weight of 48,000 that was recognized by 7 of 10 sera from patients with disseminated candidiasis . Immunoprecipitation experiments with labeled proteins from region A and 51 human sera also demonstrated the presence of a major antigen whose apparent molecular weight is 48,000 to 52,000 . The 48- to 52-kilodalton protein is an abundant protein in region A and is the most frequently recognized protein by antibodies in the sera of patients with disseminated candidiasis . Patients with disseminated candidiasis had significantly higher levels of antibody (immunoglobulin G) (P less than 0.001) directed against the 48- to 52-kilodalton protein than did patients with noninvasive forms of candidiasis, patients with other fungal infections, or normal, healthy persons. Antimicrob Agents Chemother, 1984 Feb, 25(2), 281 - 2 Ketoconazole in the prevention of experimental candidal vaginitis; Sobel JD et al.; The prophylactic and therapeutic activities of ketoconazole were evaluated in rats inoculated intravaginally with Candida albicans . Daily doses of 2.5 mg/kg initiated 48 h before challenge and continued for 48 h thereafter protected 80% of the rats against infection . A similar result in rats with established infection was attained with daily doses of 5.0 mg/kg. N Engl J Med, 1984 Jan 12, 310(2), 76 - 81 Acquired immunodeficiency syndrome in infants; Scott GB et al.; Fourteen infants with clinical and laboratory features of an acquired immunodeficiency syndrome were identified in a single metropolitan area from November 1980 to July 1983 . Patients were predominantly of Haitian parentage, although two cases occurred in offspring of non-Haitian intravenous drug abusers . Only one patient had received a blood transfusion before the development of clinical findings . The predominant clinical findings included failure to thrive, persistent infection of the oral mucosa by Candida albicans, chronic pulmonary infiltrates, hepatosplenomegaly, lymphadenopathy, and diarrhea . Immunologic studies showed most of the infants to have inverted ratios of T-cell subsets, greatly increased immunoglobulin levels, and circulating immune complexes . Lymphopenia was not common, as it is in adult patients . Infectious agents responsible for opportunistic infections in this series included Pneumocystis carinii, herpesviruses, particularly cytomegalovirus, and C . albicans . Bacterial infections were common, and gram-negative sepsis was the major cause of death in the seven infants who have died . At autopsy, two infants had disseminated lymphadenopathic Kaposi's sarcoma . These observations suggest the likelihood of transplacental, perinatal, or postnatal transmission of an as yet unidentified infectious agent that causes this disease. Zentralbl Gynakol, 1984, 106(9), 573 - 84 {Studies on the mycotic and bacterial risk of contamination and the use of nipagin in the artificial insemination of cryosperm}; Glander HG et al.; Primary bacterial and mycological contamination was studied in random human ejaculates . After various phases of cryopreservation secondary microbiological contamination was investigated . Furthermore, semen samples of several donors were inoculated with suspension of different concentrations of yeasts and with the test bacteria Escherichia coli K12 and Staphylococcus aureus SG 511 . Microbiological results were then compared before an after cryopreservation . The cryopreserving process was carried out with and without antibiotics to test the antibacterial effectiveness of antibiotics under these conditions . Moreover, we investigated the usability of a chemical preservative (Nipagin) at cryopreservation . The following results were obtained: 9.8 per cent of samples showed primary mycological contamination (1.9 per cent with Candida albicans) . Cryopreservation reduced the concentration of fungi by more than 90 per cent on average . The bacteriological investigations have shown, that with one exception the semen was without pathogenetic bacteria . This situation was altered scarcely during the cryopreserving process (also by use of cryoprotective medium without antibiotics) . Out of 25 ejaculates 11 had primary non-pathogenetic bacteria . Test bacteria inoculated into semen were not influenced by the addition of antibiotics to the cryoprotective medium (CPM) . Nipagin prevented respectively reduced a bacterial or a mycological contamination of the CPM during a storage of 14 days dependent of nipagin concentration but reduced the motility of human spermatozoa after cryopreservation . The results suggest the conclusion to prefer a portionate storage without nipagin at a temperature of nearly + 1 degree C, thereby the microbiological contamination may be neglected. Sabouraudia, 1984, 22(2), 163 - 6 Treatment of experimental murine candidiasis with liposome-associated amphotericin B; Ahrens J et al.; Mice were challenged intravenously with Candida albicans, and then treated either with nothing (controls), amphotericin B-desoxycholate (AMB), or amphotericin B associated with liposomes (AMB-lipo) . AMB-lipo permitted larger doses of amphotericin B to be given, and also appeared to have no severe toxicity in the animal model . High doses of AMB-lipo were protective, but at equal doses, AMB-lipo was not as effective as commercial AMB.
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