Plant Physiol, 1994 Dec, 106(4), 1471 - 81 Characterization and expression of an antifungal zeamatin-like protein (Zlp) gene from Zea mays; Malehorn DE et al.; A cDNA clone encoding a basic thaumatin-like protein of Zea mays was recovered from a mid-development seed cDNA library . The gene, Zlp, encoded a protein that was nearly identical with maize zeamatin and alpha-amylase/trypsin inhibitor . Expression of Zlp mRNA was highest in the endosperm tissue of seed 4 weeks after pollination . Expression of zeamatin-like (ZLP) protein correlated with mRNA; also, a low basal level of ZLP expression in leaf was not appreciably induced by abiotic stresses . ZLP was expressed with its own signal peptide in insect cells and in transgenic Arabidopsis and tomato plants . ZLP was secreted in all three systems, with correct processing of the signal peptide . ZLP expressed in transgenic tomato was found to be partially subjected to a proteolytic cleavage after residue 180, by an unknown mechanism, to give a "nicked" isoform of ZLP . Purified ZLP from all three sources, as well as purified "nicked" ZLP from tomato, demonstrated fungal inhibition against Candida albicans and Trichoderma reesei, with marginal inhibition observed against Alternaria solani and Neurospora crassa. Pharmazie, 1994 Dec, 49(12), 909 - 12 Activity of some Mannich bases of conjugated styryl ketones against Candida albicans; Dimmock JR et al.; A number of Mannich bases of conjugated styryl ketones displayed activity against Candida albicans strains 3153A and B311 . Antifungal potency was influenced by the relative hydrophobicities of the molecules and on occasions by the electronic nature of the aryl substituents . The compounds inhibited one or more of the following enzymes in the glutathione metabolic pathway namely glutathione S-transferases, glutathione reductase, gamma-glutamyl transpeptidase and glutathione peroxidase . Nearly half of the compounds examined on the yeast-to-mycelium transition in C . albicans 3153A prevented this conversion from occurring. Microb Pathog, 1994 Dec, 17(6), 387 - 93 Binding of plasma fibronectin to Candida albicans occurs through the cell binding domain; Penn C et al.; Candida albicans yeast cells bind soluble human plasma fibronectin (Fn) through a glycoprotein receptor (adhesin) located on the cell surface . This work demonstrates that a 120 kDa proteolytic fragment of Fn encompassing the cell binding domain binds more avidly to the yeast cell adhesin than does the parent Fn molecule . The presence of binding of Fn fragments containing heparin- and gelatin-binding domains of Fn could not be detected . The binding of the 120 kDa fragment is inhibited by a monoclonal antibody to the cell binding domain containing the amino acid sequence, Arginine-Glycine-Aspartic acid (RGD) as well as by an RGD-containing approximately 23-mer Fn peptide, but not with heparin or GRGDSPL . The fact that the cell binding domain of soluble Fn binds more avidly than does the parent molecule may explain the difference in the interaction of soluble Fn and immobilized Fn with Candida . It is possible that, upon immobilization, Fn may expose domains of the molecule previously unexposed when the molecule is in the soluble state. J Med Vet Mycol, 1994 Dec, 32(6), 473 - 6 Scanning electron microscope observation of adherence of Candida albicans to cultured keratinocytes; Bramono K et al.; The role of antigen 6 in the adherence process of Candida albicans serotype A to cultured keratinocytes was examined with a scanning electron microscope . The number of adhered organisms was significantly lower for the antigen 6-deficient mutant strain than for the antigen 6-positive parent strain (P < 0.001) . Fibril- or strand-like structures bridging the organisms and the keratinocytes were found to develop during the later stages of adherence. J Med Vet Mycol, 1994 Dec, 32(6), 461 - 6 The relationship between the glucose uptake system and growth cessation in Candida albicans; Cho T et al.; It is thought that dimorphic Candida albicans undergoes changes in its intracellular metabolic state prior to yeast-mycelial transformation . Cells grown in budding form to mid-exponential phase could not be induced to form germ tubes when grown in glucose medium . However, cells in which growth was initially inhibited by either starvation or inhibitors (0.1% hydroxyurea, 4% sodium malonate or 4% 2-deoxy-D-glucose) could be induced to form germ tubes in the same medium . The effects of these initial treatments on the intracellular state in mid-exponential phase cells were analysed by measuring the kinetics of D-glucose uptake . D-glucose uptake in mid-exponential phase and stationary phase cells was measured . The untreated mid-exponential phase cells exhibited only a high Km (6.9 mM) . However, mid-exponential phase cells, in which growth was initially inhibited, exhibited both a high Km (3.2-6.2 mM) and a low Km (0.40-0.78 mM) simultaneously . In addition, the stationary phase cells exhibited both a high Km (5.6 mM) and a low Km (0.56 mM) . These results suggest that there are two kinetically distinct systems of glucose transport in C . albicans and that changes in the glucose uptake system in C . albicans may be related to intracellular changes prior to transition from the budding to the mycelial form. J Med Vet Mycol, 1994 Dec, 32(6), 447 - 59 Differential release of an immunodominant 65 kDa mannoprotein antigen from yeast and mycelial forms of Candida albicans; Bromuro C et al.; The release of mannoprotein (MP) antigen from Candida albicans grown at 28 degrees C (yeast form) or 37 degrees C (mycelial form), and the ability of each released material to stimulate a cell-mediated immune (CMI) response by human lymphocytes in vitro, were studied . Overall, the mycelial cells released more MP per unit of dry mass increase and the released material was relatively enriched with MP constituents of lower molecular mass with respect to the material released from yeast cells . Moreover, the mycelial MP contained a 65 kDa component (MP65) which was the largely predominant MP recognized by a rabbit anti-mycelium antiserum . When peripheral blood mononuclear cells from normal human subjects were stimulated in vitro with graded amounts of yeast or mycelial MP, the latter was about one order of magnitude more potent than the former in inducing lymphocyte proliferation . Following MP separation by gel permeation chromatography, an appreciable CMI response was stimulated only by the MP65-containing MP fractions, and to a degree apparently related to the amount of MP65 itself . Altogether, these data confirm our previous findings about the MP65 antigen as a major target of CMI response to C . albicans, and demonstrate that this antigen is released predominantly by the mycelial cells of the fungus in vitro. J Med Vet Mycol, 1994 Dec, 32(6), 437 - 45 Helical growth of hyphae of Candida albicans; Sherwood-Higham J et al.; When grown on a range of surfaces in conditions favouring hyphal growth, hyphae of Candida albicans grew in a right-handed helical fashion . This phenomenon was observed with eight strains and with two nutrient media . It is suggested that this is a result of rotation of the hyphal apex as it extends, which on some surfaces results in a helical hyphal wall, but which in a liquid results in a straight hypha . The consequence is that on a surface, a helically growing hypha will be exposed to a more diverse environment than a straight hypha . This phenomenon may have significance in the colonization of tissue by C . albicans. J Antimicrob Chemother, 1994 Dec, 34(6), 975 - 87 Comparative capacity of four antifungal agents to stimulate murine macrophages to produce tumour necrosis factor alpha: an effect that is attenuated by pentoxifylline, liposomal vesicles, and dexamethasone; Louie A et al.; The efficacy and toxicity of certain antifungal agents may be related to their ability to induce the production of cytokines by mononuclear phagocytes . The capacity of incremental concentrations of fluconazole, 5-fluorocytosine (5-FC), amphotericin B (AmB), and liposomal AmB (LAB) to stimulate murine peritoneal and RAW 264.7 macrophages to secrete tumour necrosis factor alpha (TNF alpha) after 3, 6 and 24 h incubation was assessed by L929 cytotoxic bioassay . Fluconazole (2.5-40 mg/L) and 5-FC (25-100 mg/L) did not have a stimulatory effect . However, AmB (0.25-10 mg/L) elicited TNF alpha production by macrophages . This response was concentration-dependent, and peak TNF alpha levels were detected between 3 and 6 h . This effect was attenuated by incorporation of AmB into liposomal vesicles and by pretreating macrophages with pentoxifylline or dexamethasone . AmB I mg/L in combination with 1 x 10(6) cfu of Candida albicans stimulated peritoneal macrophages to produce similar quantities of TNF alpha as AmB alone, and two- to four-fold more TNF alpha than C . albicans alone . Thus, this study suggests that: (1) the immunomodulatory activity and toxicities of AmB, in part, may be attributed to the capacity of this drug to stimulate macrophages to secrete TNF alpha, (2) the TNF alpha that is produced by macrophages in response to AmB may have clinical relevance even in the face of C . albicans infection, and (3) the failure of fluconazole, 5-FC, and LAB to elicit a TNF alpha response may explain their improved side-effect profiles. Yeast, 1994 Dec, 10(12), 1647 - 51 CAN1, a gene encoding a permease for basic amino acids in Candida albicans; Sychrova H et al.; The first gene coding for an amino-acid permease of Candida albicans was sequenced . The DNA fragment complementing the lysine-permease deficiency was 3385 bp long . An open reading frame of 1713 nucleotides was found encoding a protein of 571 amino acids, with a calculated molecular weight of 63,343 . Analysis of the deduced primary structure revealed ten membrane spanning regions and three potential N-glycosylation sites . The protein sequence is strongly homologous to both permeases for basic amino acids (Can1 and Lyp1) of Saccharomyces cerevisiae . C-terminal part of another ORF (105 aa), highly homologous to the gene HAL2 of S . cerevisiae, was found 133 bp downstream, and in tail-to-tail orientation to the permease gene. J Chemother, 1994 Dec, 6(6), 408 - 11 Murine yeast gut flora affected by tetracycline, metronidazole and norfloxacin; Samonis G et al.; Three-month old, male Crl:CD1(ICR) BR mice, were fed food containing Candida albicans, while other mice of the same type were fed regular food . Both groups of mice were subsequently given orally either antibiotics or normal saline for a 10-day period . The stools of all mice were cultured before, at the end, and one week after the end of the antibiotic treatment, to determine the level of gut colonization by the yeast . The mice fed Candida and treated with antibiotics had substantially higher Candida counts in their stools than control mice fed C . albicans and treated with saline . The concentrations of Candida in the stools of mice treated with tetracycline were much higher when compared to those of mice treated with metronidazole and norfloxacin . Tetracycline was associated with a statistically significant increase of gastrointestinal Candida colonization . Yeast was not found in the stools of mice fed regular food and treated with antibiotics or saline . Histopathologic examination did not reveal dissemination of Candida in the visceral organs of any mouse. C R Acad Sci III, 1994 Dec, 317(12), 1107 - 13 Enhanced resistance against lethal disseminated Candida albicans infection in mice treated with polar glycopeptidolipids from Mycobacterium chelonae (pGPL-Mc); Lagrange PH et al.; Intraperitoneal administration of polar glycopeptidolipids extracted from Mycobacterium chelonae (pGPL-Mc) greatly increased the resistance of mice against a lethal disseminated Candida albicans infection . This enhanced resistance was demonstrated by an increase in the number of survivors and the prolongation of the mean survival time of animals following a lethal challenge . These effects were dependent upon the infective dose of Candida albicans, the dose of pGPL-Mc and the timing of its administration . This enhanced resistance was correlated with the development and persistence of a hyperleukocytosis, associated with a long lasting increase in the number of polymorphonuclear neutrophils . On the contrary, no candidacidal effect of the serum collected from pretreated mice was observed; suggesting that the ability of pGPL-Mc to increase resistance against Candida albicans infection is likely to be mediated by polymorphonuclear neutrophils . These results confirm previously described immunostimulating properties of pGPL-Mc and open the way for the evaluation of its effect in the prevention of opportunistic infections in neutropenic patients. Braz J Med Biol Res, 1994 Dec, 27(12), 2721 - 32 Pathogenicity of Candida albicans: quest for a molecular switch; Datta A; Candida albicans is an opportunistic pathogen of human beings and other mammals . Two other features, besides its pathogenicity, have made it a popular organism for study . It exists in different cellular forms and can change from one form to another, depending on growth conditions . Thus, it is being used as a model system to study cellular differentiation . It can also heritably and reversibly switch its cellular and colony morphologies. Eur J Cell Biol, 1994 Dec, 65(2), 402 - 7 Identification of beta-1,6-glucosylated cell wall proteins in yeast and hyphal forms of Candida albicans; Kapteyn JC et al.; Several cell wall proteins released from yeast and hyphal cells of Candida albicans by laminarinase reacted with an affinity-purified antiserum raised against beta-1,6-glucan . Binding of the antiserum was competitively inhibited by beta-1,6-glucan, but not by beta-1,3-glucan or isolated N-chains . Immunodetection was completely abolished when the proteins were treated with periodate . These results demonstrate that the laminarinase-released wall proteins of C . albicans possess an epitope consisting of beta-1,6-linked glucose residues . The yeast form of C . albicans contained four beta-1,6-glucosylated wall proteins, an Endo H-resistant protein of 125 kDa and three glycoproteins which became only detectable after Endo H digestion and had a molecular mass of 320, 170 and 44 kDa, respectively . As for the hyphal form, a different set of beta-1,6-glucosylated wall proteins was found consisting of two Endo H-resistant glycoproteins of 125 and 80 kDa, respectively, and two glycoproteins that after Endo H digestion had a molecular mass of 320 and 38 kDa, respectively . Sodium dodecyl sulfate-extractable wall proteins and medium proteins did not react with the beta-1,6-glucan antiserum . The beta-1,6-glucan epitope could be removed by aqueous hydrofluoric acid indicating that the epitope is phosphodiester-linked to the cell wall proteins . It is speculated that the epitope forms part of a GPI-anchor and might be involved in the anchoring of mannoproteins into the cell wall. Infect Immun, 1994 Dec, 62(12), 5213 - 9 Adherence of Pseudomonas aeruginosa and Candida albicans to glycosphingolipid (Asialo-GM1) receptors is achieved by a conserved receptor-binding domain present on their adhesins; Yu L et al.; Pseudomonas aeruginosa, a gram-negative bacterium, and Candida albicans, a dimorphic yeast, are evolutionarily distant microorganisms which can utilize filamentous structures termed pili and fimbriae, respectively, to mediate adherence to glycosphingolipids (asialoganglioside-GM1) receptors . The mechanism of adherence to glycosphingolipid receptors was investigated in these studies . By using monoclonal antibodies (MAbs) against purified pili of P . aeruginosa PAK (PK99H) and monospecific anti-peptide antibodies against the PAK pilin peptides {anti-PAK(128-144) and anti-PAK(134-140)}, we demonstrated that these antibodies agglutinated C . albicans whole cells and cross-reacted with C . albicans fimbriae in immunoblots . A control MAb, PKL1, and anti-PAK(75-84) peptide antibodies failed to agglutinate C . albicans whole cells or cross-react with the fimbrial proteins . Conversely, the anti-C . albicans fimbrial MAb Fm16, but not Fm34, agglutinated P . aeruginosa PAK whole cells and Western blots (immunoblots) . The interactions between PK99H and Fm16 and their respective homologous antigens were competitively inhibited by heterologous antigens; this demonstrated that the interactions between the antibodies and the heterologous antigens, i.e., PK99H with C . albicans fimbriae and Fm16 with P . aeruginosa pili, were highly specific and suggested that both adhesins share a common antigenic determinant . The immunological cross-reactivity between Fm16 and P . aeruginosa PAK pilin is localized onto the PAK(134-140) region as shown by a competitive enzyme-linked immunosorbent assay . The PAK(134-140) region of PAK pilin contains the epitope recognized by PK99H and also constitutes part of the receptor-binding domain of the pilus adhesin . Thus, the results from these studies suggest that common cell surface receptors are recognized by the P . aeruginosa and C . albicans adhesins because of a conserved receptor-binding domain on the adhesins. Ned Tijdschr Geneeskd, 1994 Nov 19, 138(47), 2353 - 6 {Potentiation of digoxin by itraconazole}; Meyboom RH et al.; The case is reported of a 71-year-old woman with clinical signs of digoxin intoxication, presumably developing as a result of the simultaneous use of digoxin for cardiac abnormalities and itraconazole for infection with Candida albicans . Five similar experiences have previously been reported in the literature . Itraconazole may induce a decreased elimination of digoxin, but the mechanism of interaction is still unknown . Comedication and renal function may perhaps contribute to the degree of interaction . When itraconazole is needed in a patient also using digoxin the blood level of the latter drug should be monitored; the daily dose of digoxin may have to be decreased to only one-quarter of the original . Nausea and anorexia may be mistaken for side effects of itraconazole and be overlooked as early signs of digoxin intoxication. N Engl J Med, 1994 Nov 17, 331(20), 1325 - 30 A randomized trial comparing fluconazole with amphotericin B for the treatment of candidemia in patients without neutropenia . Candidemia Study Group and the National Institute; Rex JH et al.; BACKGROUND . Amphotericin B has long been the standard treatment for candidemia, but its use is complicated by its toxicity . More recently, fluconazole, a water-soluble triazole with activity against candida species and little toxicity, has become available . We conducted a multicenter randomized trial that compared amphotericin B with fluconazole as treatment for candidemia . METHODS . To be eligible, patients had to have a positive blood culture for candida species, a neutrophil count > or = 500 per cubic millimeter, and no major immunodeficiency . Patients were randomly assigned to receive either amphotericin B (0.5 to 0.6 mg per kilogram of body weight per day) or fluconazole (400 mg per day), each continued for at least 14 days after the last positive blood culture . Outcomes were assessed by a group of investigators blinded to treatment assignment . RESULTS . Of the 237 patients enrolled, 206 met all entry criteria . The most common diagnoses were renal failure, nonhematologic cancer, and gastrointestinal disease . There was no statistically significant difference in outcome: of the 103 patients treated with amphotericin B, 81 (79 percent) were judged to have been treated successfully, as were 72 of the 103 patients treated with fluconazole (70 percent P = 0.22; 95 percent confidence interval for the difference, -5 to 23 percent) . The bloodstream infection failed to clear in 12 patients in the amphotericin group and 15 in the fluconazole group; the species most commonly associated with failure was Candida albicans . There were 41 deaths in the amphotericin group and 34 deaths in the fluconazole group (P = 0.20) . Intravascular catheters appeared to be the most frequent source of candidemia . There was less toxicity with fluconazole than with amphotericin B . CONCLUSIONS . In patients without neutropenia and without major immunodeficiency, fluconazole and amphotericin B are not significantly different in their effectiveness in treating candidemia. FEMS Microbiol Lett, 1994 Nov 15, 124(1), 99 - 105 Coordination of germ tube formation and surface antigen expression in Candida albicans; Chaturvedi VP et al.; If the determinants of shape and cell wall topography are independently regulated and induced in germ tube formation in Candida albicans, these processes may be separable in a non-germ tube forming strain . The expression of several preferentially expressed hyphal surface components in a parental, non-germ tube forming variant, and a germ tube forming revertant strain were examined by indirect immunofluorescence . The proportion of germ tubes expressing the determinants and the morphological localization of expression was similar . Few yeast cells in germ tube cultures bound probes and there was no increase in binding by yeast cells of the variant strain . Extraction with beta-mercaptoethanol prior to analysis had little effect on probe binding and the shape of yeast cells were similar . These observations suggest the ability to promote apical expansion in germ tube formation and surface expression of certain markers were coordinately regulated. Arch Pathol Lab Med, 1994 Nov, 118(11), 1115 - 8 Touch cytology . A quick, simple, sensitive screening test in the diagnosis of infections of the gastrointestinal mucosa; Debongnie JC et al.; To assess the role of touch cytology (imprint from endoscopic biopsy specimens) in the diagnosis of mucosal infections of the gastrointestinal tract, we reviewed all records and specimens of patients seen during a 30-month period . Touch cytology was performed by rolling biopsy specimens on glass slides . After air fixation, a rapid staining method similar to May-Grunwald-Giemsa was used . The following infections and pathogens were diagnosed (in decreasing order of frequency): Helicobacter pylori gastritis (n = 53), Candida albicans esophagitis (n = 40), Giardia lamblia (n = 13), Gastrospirillum hominis (n = 11), and Blastocystis hominis (n = 8) . The smear was positive in 45 patients with H pylori, in 35 patients with C albicans, in nine patients with G lamblia, in 11 patients with G hominis, and in eight patients with B hominis . Cytology was the only positive test in eight, nine, four, seven, and eight patients, respectively, and increased thus the diagnostic yield obtained by histologic examination. Arch Dermatol, 1994 Nov, 130(11), 1393 - 401 IgE-mediated hypersensitivity and contact sensitivity to multiple environmental allergens in atopic dermatitis; Tanaka M et al.; BACKGROUND AND DESIGN: Atopic dermatitis (AD) is a chronic eczematous skin disease that develops in a patient with atopic diathesis, which is characterized by an increased liability to produce IgE antibodies for environmental allergens mostly derived from other living organisms . Experimentally, eczematous skin lesions cannot be induced by immediate IgE-mediated reactions alone . They are produced by cell-mediated allergic contact reactions, and recently contact sensitivity to various environmental allergens has been demonstrated in patients with AD . However, the pathologic role of IgE-mediated skin hypersensitivity or that of delayed-type hypersensitivity to various environmental allergens in AD is not fully evaluated . They have been studied separately and against only specific allergens . Thus, we performed a combined testing procedure consisting of radioallergosorbent test, prick, and scarification patch tests for eight environmental allergens in 97 Japanese adult patients with AD; 48 of them had a history of atopic respiratory diseases (ARD), whereas the remaining 49 had no history of ARD (pure AD) . RESULTS: Patients with AD, particularly those with ARD (AD+ARD), showed a higher incidence of positive radioallergosorbent test and prick test results as well as patch test results against multiple environmental allergens than healthy age-matched control subjects . Among them, we found a significantly high positive correlation between radioallergosorbent test scores and patch test reactions to two allergens, Japanese cedar, and Dermatophagoides farinae allergens in patients with AD . However, the patients with AD displayed a significantly lower incidence of positive patch test reactions to Candida albicans allergen than the healthy control subjects . Patients with AD with negative C albicans patch tests tended to have higher levels of total serum IgE including anti-C albicans IgE antibody . We found negative correlations between total serum IgE levels including specific antibodies and patch test reactions to C albicans allergen . CONCLUSIONS: Except for the dissociated reactivities to C albicans allergen consisting of decreased contact sensitivity and heightened IgE response, generally both IgE-mediated skin hypersensitivity and delayed-type hypersensitivity to various environmental allergens are pronounced in patients with AD . The combined use of these in vivo and in vitro tests is useful to estimate the immunological state of patients with AD. Radiol Clin North Am, 1994 Nov, 32(6), 1135 - 45 Infectious esophagitis; Yee J et al.; Infectious esophagitis is most often seen in patients with impaired host resistance . It has become a particular problem in the growing AIDS population . The three most commonly encountered opportunistic infections of the esophagus are Candida albicans, herpes simplex virus, and cytomegalovirus . Candida is the single leading cause of infectious esophagitis . Tuberculous and bacterial esophagitis and other unusual fungal infections of the esophagus are uncommon. J Nutr, 1994 Nov, 124(11), 2156 - 62 Enteral formula composition does not affect response to lethal infectious challenge in mice; Alder JD et al.; The effects of enteral formulations on the response of mice to infectious challenge with Listeria monocytogenes, influenza A or Candida albicans were studied to test the efficacy of specialized ingredients . CF-1 outbred female mice (12-15 g) were fed nonpurified diet (Purina No . 5002) or commercially available liquid formulas: Osmolite HN, Perative or Impact . There were no differences between the groups fed the liquid formulas with regards to mean survival time or percentage of survivors in any of these models of infection . Examination of spleens from the groups challenged with L . monocytogenes, lungs from mice infected with Influenza A and kidneys from the groups challenged with C . albicans revealed no differences in cure rate of survivors . Pre-feeding periods of up to 8 d before infection produced similar results for mice fed enteral formulations compared to nonpurified diet . Contrary to previous reports, the use of Impact did not improve resistance to disease in mice challenged with lethal doses of L . monocytogenes, as compared with mice fed Osmolite HN . Additionally, mice fed Impact, Perative, or nonpurified diet responded similarly to challenge with L . monocytogenes, C . albicans or influenza A . The results indicate that these acute lethal animal models of infectious challenge may be of limited use to distinguish effects of modified nutrient composition of enteral formulas. Eur J Biochem, 1994 Nov 1, 225(3), 1073 - 9 Characterisation of D-arabinono-1,4-lactone oxidase from Candida albicans ATCC 10231; Huh WK et al.; D-Erythroascorbic acid was detected from the cell extracts of a dimorphic fungus, Candida albicans . Its concentration in yeast cells grown at 25 degrees C was estimated to be about 0.45 mumol/ml cell water . D-Arabinono-1,4-lactone oxidase, which catalyses the final step in the biosynthesis of D-erythroascorbic acid, was purified 639-fold from the mitochondrial fraction of C . albicans to apparent homogeneity, with an overall yield of 21.2%, by a purification procedure consisting of Triton X-100 solubilisation, ammonium sulphate precipitation, anion-exchange, hydrophobic-interaction, gel-filtration and dye-ligand chromatographies . Gel-filtration chromatography and polyacrylamide-gradient gel electrophoresis in the presence of deoxycholate gave apparent molecular masses of 110 kDa and 84.4 kDa, respectively . SDS/PAGE showed only one protein band corresponding to a molecular mass of 66.7 kDa . Considering the binding of detergents, the enzyme is suggested to be a single polypeptide . The enzyme showed a typical fluorescence excitation spectrum of a flavin-containing enzyme . The flavin was not released by treatment with SDS, CCl3CO2H or boiling, indicating that it may be covalently bound to the enzyme protein . The enzyme was optimally active at 40 degrees C and at pH 6.1 . The enzyme was stable in the range pH 7.5-10 . An apparent Km value for D-arabinono-1,4-lactone was 44.1 mM . L-Galactono-1,4-lactone, L-gulono-1,4-lactone and L-xylono-1,4-lactone could also serve as substrates . Competitive inhibition was demonstrated with D-glucono-1,5-lactone, L-arabinono-1,4-lactone, D-galactono-1,4-lactone and D-gulono-1,4-lactone . p-Chloromercuribenzoate, N-ethylmaleimide, iodoacetic acid, iodoacetamide and divalent metal ions such as Cd2+, Hg2+, Mn2+ and Zn2+ exhibited inhibitory effects on the enzyme. Surgery, 1994 Nov, 116(5), 868 - 76 Intestinal microbial translocation: immunologic consequences and effects of interleukin-4; Shou J et al.; BACKGROUND . Administration of a chemically defined, liquid, elemental diet (CDD) results in intestinal microbial translocation, but the immunologic consequences of this process are unclear . This study evaluated the effects of CDD feeding and interleukin-4 (IL-4) administration on mesenteric lymphocyte, peritoneal macrophage (PMO), and hepatic Kupffer cell (KC) functions . METHODS . BALB/C mice (n = 60) were randomized to receive a paired feeding of regular diet (RD) or a CDD for 14 days . Mesenteric lymph nodes (MLN) and cecum were cultured for bacteria . Mixed lymphocyte response and cytotoxic T-lymphocyte function of MLN lymphocytes were assayed . PMO and KC were harvested to measure tumor necrosis factor production, macrophage binding of fluorescent-labeled lipopolysaccharide, and Candida albicans phagocytosis (CAP) and killing (CAK); KC-hepatocyte interaction was assessed by hepatocyte protein synthesis . In a second study 75 BALB/c mice received RD, CDD, and CDD+IL-4 (30,000 units/mouse intraperitoneally) . MLN lymphocyte and PMO functions were measured and intestinal immunoglobulin A levels were determined . RESULTS . Oral feeding of a CDD resulted in significant impairment of mesenteric lymphocyte mixed lymphocyte response and cytotoxic T-lymphocyte functions and decreased PMO tumor necrosis factor production, fluorescent-labeled lipopolysaccharide binding, CAP, and CAK . KC function was preserved in CDD-fed mice . Administration of IL-4 significantly reduced the incidence of bacteria positive MLN and increased PMO superoxide production, CAP, CAK, and MLN lymphocyte mitogenesis . CONCLUSIONS . Use of IL-4 may be beneficial in situations where intestinal microbial translocation contributes to sepsis. Infect Immun, 1994 Nov, 62(11), 5154 - 6 Production of a hemolytic factor by Candida albicans; Manns JM et al.; Candida albicans exhibits hemolytic activity when grown on glucose-enriched blood agar . This activity is present on intact organisms, and it is secreted into the culture medium . Hemoglobin released from lysed erythrocytes can restore the transferrin-inhibited growth of C . albicans . We conclude that C . albicans expresses a hemolytic factor which allows it to acquire iron from host erythrocytes. Infect Immun, 1994 Nov, 62(11), 5027 - 31 Molecular and functional analysis of the LYS1 gene of Candida albicans; Garrad R et al.; The LYS1 gene of Candida albicans has been localized to a 1.8-kb DNA fragment present on the plasmid YpBRG2 . YpBRG2 has been shown to complement the saccharopine dehydrogenase mutant Stx4-4A of Saccharomyces cerevisiae . Transformants of S . cerevisiae Stx4-4A exhibited significant saccharopine dehydrogenase activity, and cells that had lost YpBRG2 after nonselective growth had no enzyme activity . The DNA sequence of the LYS1 gene has been determined . The LYS1 DNA contains typical yeast upstream regulatory sequences, including the GCN4 motif and candidate sequences responsible for transcription termination within the 3' noncoding region . The fragment contained an open reading frame of 1,146 nucleotides coding for a putative protein of 382 amino acids . The open reading frame has 60% identity at the nucleotide level and 71% similarity at the amino acid level to the LYS5 gene of Yarrowia lipolytica, which is believed to code for saccharopine dehydrogenase . A peptide of 11 amino acids has been found, which is present in S . cerevisiae, Y . lipolytica, and C . albicans . This peptide can be expanded to 16 amino acids when the sequences from Y . lipolytica and C . albicans are compared . A motif responsible for the binding of the adenosine residue of NADH has been described previously and is very similar to this peptide, which may be the site of NADH binding in the saccharopine dehydrogenase of C . albicans. J Perinatol, 1994 Nov-Dec, 14(6), 450 - 3 Focal intestinal perforation in the extremely-low-birth-weight infant; Novack CM et al.; The purposes of this report were to (1) document the clinical and laboratory features of 11 extremely-low-birth-weight (ELBW) infants with focal intestinal perforation and (2) investigate the clinical events possibly associated with these perforations by examining matched pairs of infants with and without focal intestinal perforation . During the study period 173 infants with birth weights between 600 and 1000 gm were admitted to the neonatal intensive care nursery . Eleven of these ELBW infants had focal intestinal perforations and formed the study group . These infants were matched with 11 ELBW infants who did not have intestinal perforations or signs of inflammatory bowel disease . The matched pairs were similar in all respects except for a significantly higher percent increase in blood urea nitrogen level after treatment with indomethacin (Wilcoxon signed-rank test, p < 0.02) in infants with intestinal perforation . At laparotomy the perforations were noted to be focal, often multiple, and on the antimesenteric border of the distal ileum . None of the infants showed clinical, radiographic, or intraoperative findings that were consistent with classifications for necrotizing enterocolitis (NEC) . The incidence of focal intestinal perforation in ELBW infants was 6% versus 2% for typical NEC . In addition, four of the 11 infants with intestinal perforation had positive cultures for either Staphylococcus epidermidis or Candida albicans, whereas none of the infants without perforation had positive cultures during the study period (Fisher's exact test, p < 0.09) . We conclude that the clinical presentation and the characteristic intestinal lesions in this group of ELBW infants are distinct from those in typical cases of NEC.(ABSTRACT TRUNCATED AT 250 WORDS) Curr Genet, 1994 Nov-Dec, 26(5-6), 415 - 21 MluI site-dependent transcriptional regulation of the Candida albicans dUTPase gene; McIntosh EM et al.; The Candida albicans dUTP pyrophosphatase (dUTPase) gene DUT1 has been isolated by genetic complementation in S . cerevisiae . It was found to encode a 17-kDa protein similar in amino-acid sequence to dUTPases isolated from other systems . The gene was adapted for expression in E . coli and yielded a soluble and highly-active enzyme which is easily purified . The 5' flanking sequence of DUT1 contains an MluI site typical of MCB cell-cycle-dependent UAS elements of budding and fission yeast . We found the gene to be cell-cycle-regulated when expressed in S . cerevisiae, and deletion of the MluI site resulted in a large reduction of DUT1 transcription in C . albicans . These results suggest that MCB elements are functionally conserved in this pathogenic fungus . Based on the vital role that dUTPase plays in DNA replication, the C . albicans enzyme may be a potentially useful target for the development of novel anti-fungal compounds. Antimicrob Agents Chemother, 1994 Nov, 38(11), 2605 - 11 Effects of naftifine and terbinafine, two allylamine antifungal drugs, on selected functions of human polymorphonuclear leukocytes; Vago T et al.; Many antimycotic agents negatively affect the natural immune response . Typically, these drugs impair polymorphonuclear leukocyte (PMN) production of superoxide anion, chemotaxis, or the killing of pathogens . Allylamines are a new class of antimycotic compounds with a new mechanism of antifungal action, i.e., inhibition of the fungal squalene epoxidase . The trial that we describe aimed to evaluate the effects of two allylamines, terbinafine and naftifine, on selected functions of PMNs, i.e., superoxide anion production, chemotaxis, and killing of Candida albicans blastospores . Terbinafine and naftifine on their own did not affect superoxide anion production when they were added to PMNs . When PMNs were preincubated with allylamines and were then stimulated by N-formyl-Met-Leu-Phe or phorbol 12-myristate 13-acetate, superoxide anion production was increased (priming effect) . Since intracellular free calcium (Ca2+i) is involved in the control of superoxide anion production, we evaluated the effects of the allylamines on the Ca2+i concentration ({Ca2+}i) . In the presence of terbinafine or naftifine, the {Ca2+}i increased in a dose-dependent manner; the source of Ca2+i was not extracellular since it was not affected by extracellular calcium chelation with ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid . In the presence of terbinafine or naftifine, chemotaxis of PMNs was not impaired . Terbinafine and naftifine slightly but significantly increased the killing of C . albicans blastospores (P < 0.05 at 10 and 100 microM) . In conclusion, in contrast to imidazole-like drugs, the allylamine antimycotic compounds terbinafine and naftifine enhance selected functions of PMNs. Antimicrob Agents Chemother, 1994 Nov, 38(11), 2553 - 6 In vitro activity of a new antifungal triazole, D0870, against Candida albicans isolates from oral cavities of patients infected with human immunodeficiency virus; Barchiesi F et al.; We investigated the in vitro activity of a new antifungal triazole, D0870, against 100 Candida albicans isolates from the oral cavities of patients infected with human immunodeficiency virus by using a broth macrodilution method following the recommendations provided by the National Committee for Clinical Laboratory Standards (document M27-P) . All of the isolates were chosen from C . albicans isolates already tested for fluconazole susceptibility by the procedure of the National Committee for Clinical Laboratory Standards . Fifty isolates were considered fluconazole susceptible (MICs, < or = 4 micrograms/ml), and 50 isolates were considered fluconazole resistant (MICs, > or = 8 micrograms/ml) . The in vitro data demonstrated that D0870 had good activity against isolates tested; for 90% of all strains of C . albicans, MICs were 0.5 micrograms/ml . However, the D0870 MICs for the fluconazole-susceptible isolates were lower than those for the fluconazole-resistant isolates; MICs for 50 and 90% of the isolates tested were < or = 0.0078 and 0.06 micrograms/ml, respectively, for fluconazole-susceptible isolates and 0.25 and 2 micrograms/ml, respectively, for fluconazole-resistant isolates (P < 0.001) . Our data suggest that this new triazole could represent a valid alternative in the treatment of oral candidiasis in human immunodeficiency virus-infected patients. Lipids, 1994 Nov, 29(11), 793 - 7 Structural and functional role of lipids in yeast and mycelial forms of Candida albicans; Goyal S et al.; The levels of total lipids, sterols and phospholipids were found to be significantly higher in the mycelial form (log phase) of Candida albicans than in the yeast form . Increased phospholipid levels in the mycelial form were due to higher levels of phosphatidylcholine, phosphatidylserine and phosphatidylinositol . Analyses of fatty acid composition also revealed higher levels of myristic acid (40%) in the yeast form, resulting in higher levels of saturated lipids than in the mycelial form . The changes in the lipid composition were also manifested in altered thermotropic phase behavior as gel-to-liquid crystalline phase transitions were observed at 36 and 27 degrees C for the lipids of the yeast and mycelial forms, respectively . These changes coincided with higher uptake rate, i.e., Km and Vmax values, for the transport of L-proline and with a higher sensitivity of the mycelial form against antifungal drugs. J Clin Microbiol, 1994 Nov, 32(11), 2869 - 70 Increased phenotypic switching in strains of Candida albicans associated with invasive infections; Jones S et al.; This study reports the rates of phenotypic switching in strains of Candida albicans isolated from superficial and invasive infections . Of 19 invasive strains, 68% showed switching activity, often at very high rates, compared with only 28% of 40 strains isolated from superficial sites (P = 0.004). J Clin Microbiol, 1994 Nov, 32(11), 2646 - 54 Evolution and replacement of Candida albicans strains during recurrent vaginitis demonstrated by DNA fingerprinting; Schroppel K et al.; Southern blot hybridization with the Ca3 probe and the C fragment of the Ca3 probe was used to assess the genetic relatedness of Candida albicans strains from one patient with recurrent C . albicans infection in whom the same strain was maintained, one patient in whom the infecting strain was replaced, and their male sexual partners . In the patient in whom the infecting strain was maintained, the infecting strain exhibited a minor genetic change in each successive episode of Candida vaginitis . These genetic changes occurred in the C-fragment bands of the Ca3 hybridization pattern . In the patient in whom the infecting strain was replaced by another infecting strain, a transition infection involved a genetically mixed infecting population, and the replacement strain appeared to have originated from the oral cavity of the male partner . The results demonstrate that the infecting strains of recurrent Candida vaginitis are not genetically stable, that drug treatment can result in the selection of variants of the previously infecting strain or replacement by a genetically unrelated strain, and that the male partner can be the source of a replacement strain. Kansenshogaku Zasshi, 1994 Nov, 68(11), 1367 - 75 {Study of neutrophil dysfunctions in the elderly using a chemiluminescence method}; Aoki M; To evaluate the cause of the vulnerability to infections in the elderly, the ability of neutrophil to generate reactive oxygen species was assessed by a luminol-dependent chemiluminescence (CL) assay after stimulation with non-opsonized zymosan, Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Candida albicans and lumispheres in elderly patients aged 70 to 93 years . The integrated CL for 20 minutes of whole blood and neutrophils induced by zymosan in the elderly was significantly lower than that in healthy young adults, and the integrated CL of neutrophils induced by lumispheres was also significantly lower in the elderly aged 80 years and over . When bacterial infection occurred in the elderly, the levels of CL were elevated and decreased in the convalescence . This response is proper for host-defense mechanism against infection . However, whole blood CL response was not fully activated in any patients of the elderly during bacterial infection . In these cases lower white blood cell counts, lower neutrophil counts, or the decreased level of the serum total protein, albumin, total cholesterol or cholinesterase were observed . Relationship between malnutrition and the ability of neutrophil to generate reactive oxygen species was suggested . Furthermore, I evaluated the priming effect of lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-alpha) on whole blood CL . The CL responses stimulated with non-opsonized zymosan or P . aeruginosa were enhanced by pretreatment with TNF-alpha and LPS in healthy young adults . On the other hand, no significant priming effect was observed when blood from elderly patients were incubated with each primer . These findings suggest that the impairment in the generation of reactive oxygen species of the neutrophils and the decrease in reactivity to LPS and TNF-alpha that activate neutrophils at the site of infection and potentiate host defense against invading bacteria, may contribute to susceptibility to infection in the elderly. Enferm Infecc Microbiol Clin, 1994 Nov, 12(9), 439 - 42 {Identification of yeasts of the Candida genus with a growth inhibition system: Microring YT}; Torres-Rodriguez JM et al.; BACKGROUND: It has been observed an spectacular increasing of opportunistic Candida yeast infections . Many of them are fatal, and rapid and effective identification of the infecting species contributes to start the correct treatment . Several new methods for yeast identification have become available; Microring YT is one of these methods based on the growth inhibition by 6 different chemical products . The aim of this work is to study the performance of the test using representative clinical yeast isolates . METHODS: A total of 146 strains belonging to the 5 most common Candida species isolated in the clinical laboratory were identified using conventional methods (germ tube and chlamydospores production, and the standard API 20C AUX and 16 sugars auxonography; Institute Pasteur) and the Microring YT System . This test uses the differing susceptibilities of yeast to 6 discs mounted on a filter paper ring . The chemical products and dyes are: janus green, ethidium bromide, triphenyl tetrazolium chloride, brilliant green, cycloheximide and rhodamine 6G . The inhibition pattern of a 6 digit code is compared with a list of profiles . RESULTS: Using the Microring YT system 112 of the 146 studied strains were correctly identified with an overall concordance of 77% between this method and the standard one . The morphological study (germ tube production) increased 6% the identification of Candida albicans . Better results were obtained with C . krusei and C . parapsilosis (85% of concordance) . With C . glabrata only 59% of concordance was found . CONCLUSIONS: In spite Microring YT is a simple method, easy to perform and read, it was considered inadequate for the identification of Candida species as a routine microbiological procedure. Zhonghua Kou Qiang Yi Xue Za Zhi, 1994 Nov, 29(6), 339 - 41, 384 {Effect of candidal infection on the hyperplastic oral epithelium}; Zhang KH et al.; DMBA was used to produce oral epithelial changes, from benign hyperplasia to epithelial dysplasia of different severity in golden hamsters . Thereafter, they were inoculated with candida albicans . The result shows that candidal infection can induce epithelial dysplasia in benign hyperplasia; and in epithelial dysplasia, candidal infection will promote malignant transformation . It implies that candidal infection of the oral leukoplasia should be detected and treated. J Antimicrob Chemother, 1994 Nov, 34(5), 659 - 68 High prevalence of antifungal resistance in Candida spp . from patients with AIDS; Law D et al.; Three hundred and forty-eight isolates of Candida spp . from patients treated at a regional infectious diseases unit for AIDS, immunocompromised patients admitted to the Hope Hospital and isolates referred from around the North West of England were tested for their in-vitro susceptibility to amphotericin B, fluconazole and flucytosine using standardized methods . Candida albicans comprised 73% of isolates, Candida glabrata 10% and Candida parapsilosis 7% . Ninety-six percent of isolates were susceptible to amphotericin B and resistance to > or = 12.5 mg/L fluconazole was found in 61 (17.5%) of the 348 isolates tested . Among isolates from patients with AIDS the incidence of fluconazole resistance was 33% whereas in other patients the incidence was only 11% . Flucytosine resistance was seen in only 12 (3.4%) isolates, 11 of which were C . albicans and in 6.5% of isolates from patients with AIDS . Resistance to fluconazole and flucytosine is now sufficiently prevalent among Candida spp . isolated from patients with AIDS to warrant routine susceptibility testing of yeast isolates. Pediatr Allergy Immunol, 1994 Nov, 5(4), 240 - 3 High levels of IgA in HIV-1-perinatally-infected children . Antigen specificity and possible role of increased substance P plasma levels; Rossi ME et al.; The specificity of IgA against food, inhalant, bacterial and fungine antigens as well as for HIV-1 proteins was investigated in 14 HIV-1-infected children (CDC stage P-2) and 15 controls . IgA against food- and inhalant antigens as well as against tetanus toxoid were significantly more often present in the HIV positive children than in controls . No difference between the two groups was present for IgA against Candida albicans . A significant increase of substance P, a strong IgA synthesis inducing neuropeptide, was demonstrated in the plasma of HIV-1 infected children . In conclusion, high levels of IgA seem to reflect a complex immune dysfunction in which many factors are involved . The importance of neuroimmune dysregulation is discussed. Microbiology, 1994 Nov, 140 ( Pt 11), 2971 - 9 Candida albicans expresses a fibronectin receptor antigenically related to alpha 5 beta 1 integrin; Santoni G et al.; Cell adhesion molecules, by regulating host-micro-organism interaction, play a major role in the pathogenesis of infectious diseases . The present study was undertaken to investigate the expression of the fibronectin (FN) receptor prototype, alpha 5 beta 1 integrin, on Candida albicans and its involvement in the adhesion to FN . By immunofluorescence and fluorescence activated cell sorter (FACS) analysis, several monoclonal antibodies (mAbs) directed against human alpha 5 or beta 1 integrin subunits, or two different antisera to FN receptor positively stained C . albicans yeast and germ tube phases, this immunoreactivity increasing upon germ tube transition . Twenty-five to thirty per cent of {3H}glucose-labelled Candida yeasts specifically adhered to FN and this adhesion was increased upon germ tube transition . C . albicans yeast and germ tube forms bound to an RGD-containing 120 kDa tryptic fragment of FN and adhesion to FN was markedly inhibited by GRGDSP, but not GRGESP peptides . Moreover, binding of both C . albicans phases to FN was strongly inhibited by anti-alpha 5 SAM-1 mAb, or both anti-fibronectin receptor (FNr) antisera . Overall these results indicate that C . albicans yeast and germ tube phases express a receptor antigenically related to alpha 5 beta 1 integrin which mediates their adhesion to FN . The alpha 5 beta 1 integrin-like receptor expression on C . albicans could be relevant for fungus-host interaction and in the dissemination process of Candida infection. Infect Immun, 1994 Nov, 62(11), 5151 - 3 Endothelial cell proliferation associated with lesions of murine systemic candidiasis; Ashman RB et al.; Neovascularization is associated with tumor growth and some inflammatory diseases but has not been reported to be induced by infectious agents . In a mouse model of systemic Candida albicans infection, extensive endothelial cell proliferation was seen in the periphery of brain abscesses and in the areas of fungal pyelonephritis in the kidney . This finding is important for an understanding of the pathogenesis of fungal infections and may contribute to an analysis of the mechanisms of angiogenesis. Mol Gen Genet, 1994 Oct 28, 245(2), 212 - 7 Toxicity of a heterologous leucyl-tRNA (anticodon CAG) in the pathogen Candida albicans: in vivo evidence for non-standard decoding of CUG codons; Leuker CE et al.; Plasmids containing derivatives of the Saccharomyces cerevisiae leucyl-tRNA (tRNA(3Leu)) gene that vary in anticodon sequence were constructed and transformed into the pathogen Candida albicans and S . cerevisiae . C . albicans could readily be transformed with plasmids encoding leucyl-tRNA genes with the anticodons CAA and UAA (recognizing the codons UUG and UUA) and expression of the heterologous tRNALeu could be demonstrated by Northern RNA blotting . In contrast, no transformants were obtained if the anticodons were UAG (codons recognized CUN, UUR) and CAG (codon CUG), indicating that the insertion of leucine at CUG codons is toxic for C . albicans . All tRNALeu-encoding plasmids transformed S . cerevisiae with equally high efficiencies . These results provide in vivo evidence that non-standard decoding of CUG codons is essential for the viability of C . albicans. Gene, 1994 Oct 21, 148(2), 179 - 85 Characterization of the Candida albicans TRP1 gene and construction of a homozygous trp1 mutant by sequential co-transformation; Ostrander DB et al.; The Candida albicans TRP1 gene has been isolated by complementation of an Escherichia coli trpC mutant . Sequence analysis has revealed a single ORF (open reading frame) of 678 nucleotides (nt) . The amino acid (aa) sequence deduced from this coding region demonstrates a high degree of homology with PRAI (phosphoribosylanthranilate isomerase) enzymes of other fungi, as well as bacterial species . The gene is also analogous to other yeast TRP1 genes in that it encodes a unifunctional enzyme, whereas TRP1 in filamentous fungi encodes a tri-functional enzyme . Both chromosomal copies of the gene were disrupted by sequential integrative transformation employing co-transformation of an ade1 mutant in order to create a homozygous auxotrophic trp1,ade1 C . albicans strain . This double auxotroph was used to test the ability of the Saccharomyces cerevisiae TRP1 gene to complement the C . albicans trp1 mutation; no expression of the S . cerevisiae gene was detectable. FEMS Microbiol Lett, 1994 Oct 15, 123(1-2), 131 - 6 Structural mannoproteins released by beta-elimination from Candida albicans cell walls; Mormeneo S et al.; Mild alkaline solutions (beta-elimination), after removing the non-covalently bonded wall materials by hot SDS, released 13% and 26% of remaining wall proteins from mycelial and yeast cells of Candida albicans, respectively . When the beta-elimination was carried out after digestion of the walls with chitinase, four-fold more proteinaceous materials were released from mycelium and a similar amount in yeast walls . The solubilized materials were shown to be highly polydisperse, and endo-glycosidase H reduced their polydispersity and molecular masses, revealing different electrophoretic patterns in yeast and mycelial cell walls . The solubilized mycelial proteins carried N-glycosidic sugar chains and the epitopes recognized by two monoclonal antibodies were preserved, although showing a different behaviour in yeast walls . These results are consistent with the idea that significant amounts of intrinsic O-glycosylated mannoproteins are interconnected in the walls of C . albicans. Genitourin Med, 1994 Oct, 70(5), 308 - 10 Zinc levels of serum and cervicovaginal secretion in recurrent vulvovaginal candidiasis; Bohler K et al.; OBJECTIVE--To determine whether zinc deficiency in serum or vulvovaginal secretion is a risk factor for recurrent vulvovaginal candidiasis . DESIGN--Prospective and controlled study . SETTING--Department of Dermatology, University of Vienna . SUBJECTS--21 women who had experienced at least three documented episodes of acute vulvovaginal candidiasis within the previous 12 months . Fifteen women without anamnesis of vulvovaginal candidiasis as a control group . INTERVENTIONS--Blood samples were drawn for measurement of plasma zinc levels . Lavage of the vagina and ectocervix was performed with sterile saline solution for measurement of cervicovaginal zinc levels . MAIN OUTCOME MEASURES--Zinc levels of serum and cervicovaginal secretions were determined by flame atomic absorption spectrophotometry . RESULTS--We found no significant difference in the mean zinc concentration of plasma and cervicovaginal secretions between the recurrent vulvovaginal candidiasis and the control group . (p value for serum = 0.71, p value for secretion = 0.80) . Zinc levels of plasma and cervicovaginal secretions showed no correlation (patient group: r = -0.05, control group: r = -0.07) . CONCLUSION--It is well known that zinc not only exerts a major impact on different immune functions, but also participates in growth and morphogenesis of Candida albicans . Our results could not confirm the previous hypothesis that zinc deficiency of serum is a risk factor in recurrent vulvovaginal candidiasis . It is possible that the local zinc level of cervicovaginal secretions essentially influences antifungal activity of third generation azole antimycotics. Microbiology, 1994 Oct, 140 ( Pt 10), 2611 - 6 Regulation of the gene encoding translation elongation factor 3 during growth and morphogenesis in Candida albicans; Swoboda RK et al.; The level of the TEF3 mRNA, which encodes the fungal-specific translation elongation factor 3 (EF-3), was measured during the yeast-to-hyphal transition in Candida albicans . In contrast to a previous report, TEF3 mRNA levels were shown to change during dilution into fresh medium, increasing only transiently when dimorphism was induced by either (i) an increase in growth temperature (from 25 degrees C to 37 degrees C) combined with the addition of 10% (v/v) bovine calf serum to the medium, or (ii) an increase in growth temperature (from 25 degrees C to 37 degrees C) combined with an increase in the pH of the medium (from pH 4.5 to 6.5) . TEF3 mRNA levels also increased in control cultures under conditions where germ tubes were not formed, but they remained elevated in contrast to cultures undergoing morphological changes . TEF3 mRNA levels were not significantly affected by heat-shock, but were tightly regulated during batch growth of the yeast form, reaching maximal levels in exponential phase . Therefore, the changes in TEF3 expression that accompany the dimorphic transition in C . albicans appear to reflect the underlying physiological changes that occur during morphogenesis and are not a response to morphogenesis per se . For this reason TEF3 mRNA measurement cannot be used as a loading control in Northern analyses of dimorphic gene regulation . Comparison of TEF3 mRNA levels with the abundance of the EF-3 polypeptide indicated that the synthesis of this essential translation factor might be subject to post-transcriptional regulation. J Antibiot (Tokyo), 1994 Oct, 47(10), 1092 - 7 WF11899A, B and C, novel antifungal lipopeptides . II . Biological properties; Iwamoto T et al.; WF11899A, B and C, novel water-soluble lipopeptides related to the echinocandins, possess potent anti-Candida activities . The IC50s of the compounds against four clinical isolates of Candida albicans ranged from 0.004 to 0.03 microgram/ml by microbroth dilution assay . These compounds mildly suppressed the growth of Aspergillus fumigatus and A . niger . WF11899A, B and C showed a potent in vivo anti-Candida activity . Particularly, WF11899A was superior to cilofungin, and equal to fluconazole . 1,3-beta-glucan synthase was inhibited by these compounds at the IC50s of 0.7, 0.7 and 1.8 micrograms/ml for WF11899A, B and C, respectively . However, they hemolysed mouse red blood cells in vitro at the concentration of 62 micrograms/ml. J Antibiot (Tokyo), 1994 Oct, 47(10), 1077 - 83 The novel immunostimulant N-563, an analogue of deoxyspergualin, promotes resistance to Candida albicans infection in mice; Aoyagi K et al.; An analogue of deoxyspergualin, N-563 has an immunostimulating activity whereas the mother compound has been found to be a potent immunosuppressant . In this study, the protective effect of the analogue against C . albicans infection was investigated in normal and immunosuppressed mice . In normal mice, N-563 treatment at 10 mg/kg for 3 days prior to infection significantly prolonged the survival time . In immunosuppressed mice treated with a single dose of cyclophosphamide 4 days prior to infection, N-563 at 3 and 10 mg/kg for 3 days prior to infection also significantly prolonged the survival time of mice . In addition, it augmented the phagocytic activity of neutrophils and enhanced the delayed type hypersensitivity reaction against C . albicans . Coincidentally, N-563 appeared to protect against secondary infection with C . albicans in the delayed type hypersensitivity-positive mice. Ann Allergy, 1994 Oct, 73(4), 329 - 36 Comparison of three in vitro assays for serum IgE with skin testing in asthmatic children; Kam KL et al.; The diagnostic performance of three commercial assay kits {Phadezym RAST (PhRAST), Pharmacia CAP system (CAP), and multiple chemiluminescent assay (CLA-MAST)} for measuring serum-specific IgE was evaluated and compared using intradermal skin testing or skin prick testing as reference standards . Serum samples were obtained from allergic patients who were tested with either intradermal skin tests or skin prick tests (96 and 49 subjects, respectively) . Six different allergen extracts were tested: Dermatophagoides pteronyssinus, Candida albicans, Aspergillus, short ragweed, Bermuda grass, and cockroach mix . Results showed that when using intradermal skin testing as a reference standard, the CLA-MAST had the lowest sensitivity (75%), specificity (80%), and efficiency (85%) but the Pharmacia CAP system achieved the highest sensitivity, specificity, and efficiency (86%, 94%, and 91%, respectively) . When compared with these two relatively new assays, the Phadezym RAST had medium sensitivity (80%), specificity (92%), and efficiency (88%) . In contrast, when using skin prick testing as a reference standard, the highest specificity was achieved by Phadezym RAST (95%), followed by Pharmacia CAP system (90%), and MAST (81%) . As for the sensitivity of each test, the Phadezym RAST was the lowest (60%) and Pharmacia CAP system reached the highest sensitivity (79%); and for the efficiency test, the score was 87% for CAP, 83% for Phadezym RAST, and 75% for MAST . These results suggest, therefore, that the CAP system is the preferred test and provides a useful guide for prescription of environmental control and immunotherapy in unselected patients. Am J Med, 1994 Oct, 97(4), 339 - 46 Epidemiology of oral candidiasis in HIV-infected patients: colonization, infection, treatment, and emergence of fluconazole resistance; Sangeorzan JA et al.; PURPOSE: To study the epidemiology of oral candidiasis and the effect of treatment of thrush in human immunodeficiency virus (HIV)-infected patients . PATIENTS AND METHODS: We conducted a prospective observational study of 92 patients over 1 year, including a nonblinded, randomized treatment trial of thrush with clotrimazole troches or oral fluconazole . Oral sites were cultured monthly and when thrush occurred . Candida albicans strains were typed by contour-clamped homogeneous electric field (CHEF) electrophoresis . Changes in strains were evaluated over time and in regard to their associations with particular sites, episodes of thrush, relapse after treatment, and colonization of sexual partners . Susceptibility to fluconazole was tested and CHEF analysis was done on these strains to determine the epidemiology of fluconazole resistance . RESULTS: Yeasts colonized 84% of patients . C albicans accounted for 81% of all isolates and was separated into 34 distinct strains . Most patients had persistent carriage of 1 or 2 dominant strains of C albicans . Three couples shared strains . Nineteen different C albicans strains caused 82 episodes of thrush in 45 patients . CD4 < 200/microL was associated with development of thrush . Clinical cure rates were similar with fluconazole (96%) and clotrimazole (91%), but mycologic cure was better with fluconazole (49%) than clotrimazole (27%) . Following mycologic cure, colonization recurred with the same strain 74% of the time . Colonization with Torulopsis glabrata and Saccharomyces cerevisiae increased after treatment with either drug, but these organisms were never a sole cause of thrush . In a subset of 35 patients followed for over 3 months in whom fluconazole susceptibilities were performed, minimum inhibitory concentrations (MICs) to fluconazole increased only in those on fluconazole prophylaxis . Clinical failure of fluconazole was associated with an MIC > or = 64 micrograms/mL in 3 patients, and with an MIC of 8 micrograms/mL in 1 patient . In 2 of these 4 patients, the prior colonizing strain developed fluconazole resistance . In the other 2, new resistant strains were acquired . CONCLUSIONS: Many different strains of C albicans colonize and cause thrush in patients infected with HIV . Patients are usually persistently colonized with a single strain, and recurrences following treatment are usually due to the same strain . Transmission of strains may occur between couples . Fluconazole and clotrimazole are equally effective in treating thrush, but mycologic cure occurs more often with fluconazole . Fluconazole resistance in C albicans occurs most often in patients who have low CD4 counts and are taking fluconazole prophylactically for recurrent thrush . Fluconazole resistance may occur through acquisition of a new resistant strain or by development of resistance in a previously susceptible strain. J Med Microbiol, 1994 Oct, 41(4), 264 - 71 Human urokinase, a serine proteinase, potentiates the in-vitro growth of micro-organisms which commonly infect burn patients; Hart DA et al.; Addition of human urokinase, a serine proteinase, to in-vitro cultures of Pseudomonas aeruginosa strain M2 enhanced bacterial growth . The enhancement of growth depended on the dose of urokinase (10-12,500 units) and the enzymic activity of the protein . Other mammalian proteolytic enzymes (trypsin, chymotrypsin, polymorphonuclear leucocyte elastase, thrombin and plasmin) tested did not affect bacterial growth in vitro . Experiments with clinical isolates of Candida albicans, Klebsiella pneumoniae and Staphylococcus aureus from burn patients indicated that urokinase could enhance the in-vitro growth of all of these micro-organisms . However, some strain-to-strain variation was noted in the extent of this enhancement . These results indicate that urokinase, which could be released into burn injury sites from either damaged tissues or inflammatory cells, is capable of enhancing the growth of several micro-organisms that commonly infect patients with thermal injuries, particularly under oxygen-limited conditions and when few micro-organisms are present. J Infect Dis, 1994 Oct, 170(4), 900 - 5 The role of phagocytic cells in resistance to disseminated candidiasis in granulocytopenic mice; Jensen J et al.; This study assessed the involvement of phagocytic cells in murine resistance to disseminated candidiasis of endogenous origin . SCID mice and their immunocompetent CB.17 (BALB/c) counterparts were colonized with a pure culture of Candida albicans and treated with an antigranulocyte monoclonal antibody (anti-Gr-1), polyinosinic:polycytidylic acid (poly{I.C}), or both to impair macrophage function in vivo . Candida-colonized SCID mice were more susceptible to disseminated candidiasis after treatment with anti-Gr-1 or poly(I.C) than were CB.17 mice . Histopathology of orogastric tissues demonstrated that combined treatments with anti-Gr-1 and poly(I.C) also enhanced the susceptibility of SCID and CB.17 mice to orogastric candidiasis . These data indicate that macrophages as well as granulocytes play an important role in host resistance to mucosal and disseminated candidiasis of endogenous origin. Infect Immun, 1994 Oct, 62(10), 4679 - 81 The fibronectin adhesin of Candida albicans; Klotz SA et al.; Candida albicans possesses on its cell surface an adhesin which binds the whole viable fungus to subendothelial extracellular matrix and matrix proteins . The adhesin is composed of 75 to 80% carbohydrate and approximately 20 to 25% protein by weight . High-performance liquid chromatography of material eluted from a fibronectin-agarose affinity column demonstrates the presence of three peaks, all of which on sodium dodecyl sulfate-polyacrylamide gel electrophoresis show the presence of one protein of approximately 60 kDa . Molecular weight sizing column chromatography, however, demonstrates that the adhesin elutes with an apparent molecular mass of 42 kDa . The N terminus of the 60-kDa glycoprotein is blocked to Edman degradation . The fibronectin adhesin of C . albicans is a glycoprotein that may be present and functional as an aggregate or multimer of a 60-kDa protein. Infect Immun, 1994 Oct, 62(10), 4564 - 71 Binding of the extracellular matrix component entactin to Candida albicans; Lopez-Ribot JL et al.; We have investigated the interaction between Candida albicans and entactin, a recently characterized glycoprotein present in the extracellular matrix, especially in the basement membrane . Organisms of both the yeast and the hyphal morphologies of the fungus had the ability to bind recombinant entactin, as detected by an indirect immunofluorescence assay . Material present in the 2-mercaptoethanol cell wall extracts from both C . albicans growth forms was capable of binding to immobilized recombinant entactin in a dose-dependent manner . Binding to entactin was approximately twice that observed for laminin . Binding of an extract component(s) to entactin was partially inhibited by an Arg-Gly-Asp-Ser peptide . A polyclonal antientactin antiserum, as well as a pooled antiserum preparation raised against components present in different C . albicans cell wall extracts, completely or almost completely abolished binding . The existence of morphology-specific receptor-like molecules which bind to different domains of the entactin molecule was ruled out in a competition binding assay . The entactin-binding material(s) in the cell wall also displayed some ability to bind laminin and fibronectin, since preadsorption in the presence of these extracellular matrix components resulted in reduction of binding to entactin . Moieties with a molecular mass of approximately 25, 44, and 65 kDa present in the 2-mercaptoethanol cell wall extracts from both blastoconidia and germ tubes were detected in a ligand affinity blotting experiment as having the ability to bind entactin . Interactions between C . albicans and entactin could be important in mediating adhesion of the fungus to the host tissues and may play a role in the establishment of the disseminated form of the disease. Infect Immun, 1994 Oct, 62(10), 4226 - 32 Murine tissues exposed to cytotoxic drugs display altered patterns of Candida albicans adhesion; Lopez-Ribot JL et al.; An ex vivo adhesion assay was used to examine the binding of Candida albicans yeast cells to tissues from mice treated with cytotoxic drugs such as lipopolysaccharide and the clinically used anticancer drugs doxorubicin, cisplatin, and vincristine . No major differences were observed in binding of the fungal cells to liver and kidney tissues from treated or untreated animals . All drug-treated spleens displayed altered patterns of C . albicans adhesion compared with the control group, with yeast cells bound not only to the marginal zone but also to the white and red pulp . Immunostaining for macrophages, which are proposed as the site of normal adhesion, showed no apparent differences between the control and the experimental spleens that could account for the change in adhesion patterns . Scanning electron microscopy images suggested that yeast binding to the white pulp of treated tissue is mediated through fibers, perhaps extracellular matrix components exposed as result of the cytotoxic treatment . Exposure of new attachment sites for C . albicans in treated tissues may facilitate initiation of infection. Infect Immun, 1994 Oct, 62(10), 4107 - 11 A Candida albicans surface antigen mediating adhesion and autoaggregation in Saccharomyces cerevisiae; Barki M et al.; In a previous study (M . Barki, Y . Koltin, M . Yanko, A . Tamarkin, and M . Rosenberg, J . Bacteriol . 175:5683-5689, 1993), a 3.3-kb DNA fragment from Candida albicans which confers adhesion and autoaggregation in Saccharomyces cerevisiae was isolated and partially characterized . In this report, evidence is presented that the adhesion-autoaggregation phenotype observed in S . cerevisiae cells transformed with the candidal DNA fragment is due to expression of a C . albicans surface antigen . Rabbit antiserum, prepared against transformant S . cerevisiae cells, was adsorbed with S . cerevisiae bearing the vector alone . Immunofluorescence micrography showed that the adsorbed antiserum bound to the surface of transformant S . cerevisiae cells as well as to C.albicans cells, but only marginally to the S . cerevisiae control . The absorbed antiserum specifically inhibited autoaggregation of transformant cells . Further adsorption of the antiserum with transformant cells eliminated both inhibition and immunofluorescence . Autoaggregative activity and immunofluorescence of transformant cells were abolished following proteolytic treatment . Western blot (immunoblot) analysis of candidal extracts revealed that the absorbed antiserum recognized a major candidal antigen of ca . 30 kDa which was present on both yeast-phase and germ tube cells . The data suggest that the observed adhesion-autoaggregation phenotype is due to the presence of a specific candidal antigen on the outer surface of the transformant cells. Eur J Clin Microbiol Infect Dis, 1994 Oct, 13(10), 797 - 804 Prospective study of Candida colonization, use of empiric amphotericin B and development of invasive mycosis in neutropenic patients; Martino P et al.; The association between colonization with Candida spp., subsequent occurrence of invasive candidiasis and empiric use of amphotericin B was investigated prospectively in 139 neutropenic patients with hematologic malignancies . Treatment with amphotericin B was required in 67% of patients colonized in multiple non-contiguous body sites (multicolonized) versus 31% of patients colonized in single or contiguous sites (monocolonized) and in 21% of non-colonized patients (p = 0.0037 and p = 0.00026, respectively) . Invasive candidiasis was documented in 22.2% of multicolonized versus 4.8% of monocolonized patients and in none of the non-colonized patients (p = 0.035 and p = 0.0036, respectively) . Analysis of the spectrum of colonizing Candida spp . showed that multicolonized subjects were colonized with increased frequently by Candida albicans compared to monocolonized subjects, and that the association between multicolonization, invasive candidiasis and amphotericin B usage was statistically significant in patients colonized by Candida albicans but not in patients colonized by other Candida species . The association between Candida multicolonization and the occurrence of Candida infection seems to be confirmed by a double-blind placebo-controlled study performed in a small subgroup of the multicolonized patients treated with fluconazole. Curr Genet, 1994 Oct, 26(4), 321 - 8 Partial nucleotide sequence of a single ribosomal RNA coding region and secondary structure of the large subunit 25 s rRNA of Candida albicans; Srikantha T et al.; A rDNA cistron of Candida albicans strain WO-1 was cloned and the ITS1, ITS2, 5.8 s rDNA and 25 s rDNA coding regions sequenced in their entirety . These sequences were compared to those of three related yeast species (Saccharomyces cerevisiae, Saccharomyces carlsbergensis, and Thermomyces lanuginosus), and the 5.8 s rDNA was compared to seven additional 5.8 s rDNAs from organisms ranging in complexity from D . discoideum to H . sapiens . The C . albicans ITS regions are shorter than those of most other eukaryotes . The 25 s and 5.8 s rDNA sequences were folded into a secondary structure model based on comparative methods . In a comparison of regional similarities between the large subunit rDNAs of C . albicans, the three related yeasts and other eukaryotes, it is demonstrated that the additional sequences not present in the E . coli 23 s rDNA are more variable than the regions present in both prokaryotes and eukaryotes. J Antimicrob Chemother, 1994 Oct, 34(4), 545 - 53 Effect of rufloxacin upon non-specific immune defences: in-vitro, ex-vivo and in-vivo results; Cuffini AM et al.; This study investigated in-vitro, ex-vivo and in-vivo the immunomodulatory effects of rufloxacin . 0.5 MIC of rufloxacin significantly enhanced human macrophage phagocytosis and increased intracellular killing of Klebsiella pneumoniae in vitro . Pre-incubation of K . pneumoniae with rufloxacin made the bacteria more susceptible to both phagocytosis and intracellular killing by human macrophages than control organisms . Following pre-exposure of macrophages to 0.5 MIC of rufloxacin, there was a significant increase in the intracellular killing of K . pneumoniae compared with the controls, indicating the ability of rufloxacin to cross biological membranes and to remain active within phagocytes . Ex-vivo experiments show that iv administration of rufloxacin in mice lead to an increase in both phagocytic and microbicidal intracellular activity by phagocytes . In-vivo models of experimental infections showed that prophylactic administration of rufloxacin increased the survival of mice after challenge with Candida albicans. Indian J Pathol Microbiol, 1994 Oct, 37(4), 403 - 8 Serotyping of pulmonary isolates of Candida albicans . A preliminary study; Chande CA et al.; A total of twenty strains of Candida albicans isolated from chronic pulmonary lesions were subjected to serotyping procedure adopting the conventional agglutination reactions . Prior to serotyping all the twenty strains were isolated on at least three different occasions and were identified by the standard accepted criteria (germ tube production, colony morphology on cornmeal Tween 80 agar and sugar fermentation reactions) . Of the twenty strains, four strains belonged to serotype B and the remaining sixteen had the agglutination profile consistent with serotype A . The serotyping was undertaken with locally raised antisera against serotype A and serotype B . The proposed serotyping procedure has a definite potential in the epidemiological investigations of Candida albincans. Pediatr Infect Dis J, 1994 Oct, 13(10), 899 - 905 Use of DNA fingerprinting and biotyping methods to study a Candida albicans outbreak in a neonatal intensive care unit; Betremieux P et al.; During a 15-day period, 7 premature infants hospitalized in a neonatal intensive care unit presented with sepsis caused by Candida albicans . The local environment and hands of all 54 persons involved in the intensive care unit were examined for the presence of this organism . Five techniques were used in the analysis of the isolates recovered from blood cultures of the children, the hands of personnel and 10 control isolates . The methods used were serotype determination, genetic fingerprinting, morphotyping, resistotyping and killer yeast typing . Morphotyping and genetic fingerprinting proved to be the most discriminatory techniques, and only combined analysis of the results obtained with these various methods allowed the source of the outbreak to be identified . An isolate from the hands of a healthy staff member and isolates from infected children all belonged to the same strain. Antimicrob Agents Chemother, 1994 Oct, 38(10), 2495 - 7 Azole resistance in oropharyngeal Candida albicans strains isolated from patients infected with human immunodeficiency virus; He X et al.; For 212 oropharyngeal isolates of Candida albicans, the fluconazole MICs for 50 and 90% of strains tested were 0.5 and 16 micrograms/ml, respectively, and those of itraconazole were 0.05 and 0.2 micrograms/ml, respectively . Of 16 isolates for which fluconazole MICs were > 64 micrograms/ml, itraconazole MICs for 14 were < or = 0.8 micrograms/ml and for 2 were > 6.4 micrograms/ml . Most fluconazole-resistant strains remained susceptible to itraconazole; whether itraconazole will prove effective for refractory thrush remains to be shown. Immunology, 1994 Oct, 83(2), 268 - 73 The Candida albicans phospholipomannan induces in vitro production of tumour necrosis factor-alpha from human and murine macrophages; Jouault T et al.; We have previously identified a Candida albicans 14,000-18,000 MW antigen reacting with anti-beta-1,2-linked oligomannosides antibodies as being a phospholipomannan (PLM) . Because of the structural similarities between the C . albicans PLM and lipophosphoglycans from various microbial pathogens known to be potent tumour necrosis factor-alpha (TNF-alpha) inducers, we investigated the PLM ability to induce TNF-alpha . Incubation of human monocytic cells THP-1 with PLM led to dose-dependent production of TNF-alpha that was significantly increased by prestimulation of the cells with interferon-gamma (IFN-gamma) . Production of TNF-alpha by macrophages under PLM stimulation was confirmed by using macrophages elicited from the mouse peritoneal cavity . In all investigated conditions, PLM-induced TNF-alpha production differed significantly in both kinetics and dose dependence from lipopolysaccharide (LPS) induction used as control . It appears, therefore, that the C . albicans PLM shares functional homologies with microbial lipophosphoglycans identified as pathogenicity factors, although prestimulation of the target cells was required for the PLM-derived opportunistic pathogen to trigger the cytokine network. Mol Microbiol, 1994 Oct, 14(1), 87 - 99 Expression of seven members of the gene family encoding secretory aspartyl proteinases in Candida albicans; Hube B et al.; The opportunistic fungal pathogen Candida albicans produces secretory aspartyl proteinases, which are believed to be virulence factors in infection . We have studied the in vitro expression of seven known members of the SAP gene family in a range of strains and serotypes by Northern analysis . SAP1 and SAP3 were regulated during phenotypic switching between the white and opaque forms of the organism . The SAP2 mRNA, which was the dominant transcript in the yeast form, was found to be autoinduced by peptide products of Sap2 activity and to be repressed by amino acids . The expression of the closely related SAP4-SAP6 genes was observed only at neutral pH during serum-induced yeast to hyphal transition . No SAP7 mRNA was detected under any of the conditions or in any of the strains tested . Our data suggest that the various members of the SAP gene family may have distinct roles in the colonization and invasion of the host. Indian J Gastroenterol, 1994 Oct, 13(4), 115 - 7 Fungal colonization of untreated peptic ulcer; Ghoshal UC et al.; AIM: To evaluate the relationship between Candida and peptic ulcer . METHODS: One hundred consecutive patients with untreated peptic ulcer (81 with duodenal ulcer and 19 with gastric ulcer) were studied using histopathology, culture and fungal serology . Twenty subjects with non-ulcer dyspepsia were taken as controls . RESULTS: Forty seven patients (47%) with peptic ulcer were colonized by Candida as compared to 3 patients (15%) with non ulcer dyspepsia (p < 0.05) . Confluent growth of Candida on culture of gastric aspirate or biopsy from ulcer edge was a more sensitive method for diagnosis of peptic ulcer-associated candidiasis than histological examination . There was no significant difference in the prevalence of Candida isolation in relation to age or sex of the patients, smoking habit and alcoholism . Large ulcers (> 2 cm) were, however, more often colonized by Candida (75%) than smaller ones (43%) (p < 0.05) . Candida albicans was the commonest species isolated (60%) . Invasive candidiasis was associated with Candida agglutinin titer of 1:128 in 81% of cases . CONCLUSION: Candida colonization rate in peptic ulcer is significantly higher than in non-ulcer dyspepsia. J Oral Pathol Med, 1994 Oct, 23(9), 406 - 12 Identification of Candida albicans types related to healthy and pathological oral mucosa; Rindum JL et al.; This study comprised 100 healthy dentate adults and 53 patients with either chronic erythematous oral candidosis or oral leukoplakic lesions . The presence of yeasts was determined by microscopical examination of PAS-stained smears and by culture . Biopsy material was obtained from all lesions . The isolated yeasts were identified to species level . Strain phenotypes of 147 Candida albicans isolates were determined on the basis of the ODDS & ABBOTT procedure (25, 26) . Yeasts were found in the mouth of healthy dentate individuals both by culture and by smears . The identification of hyphae in healthy mucosa indicates that the presence of these structures is not an unequivocal sign of candidal infection . The results support the view that tobacco smoking may be a predisposing factor for candidal infection . Also, the results have shown an association between the occurrence of yeasts and the type of leukoplakic lesions . Finally, the strain differentiation has indicated an oral mycoflora in patients with candidal lesions disappearing after antimycotic treatment which was more homogeneous in composition than in patients with irreversible lesions; furthermore, certain strains may possess properties which may be important in the development of pathological conditions and premalignant changes. Eur J Obstet Gynecol Reprod Biol, 1994 Oct, 57(1), 43 - 6 Increased phagocytic activity of polymorphonuclear leukocytes during pregnancy; Barriga C et al.; Many immunological parameters are depressed during pregnancy . For this reason, an evaluation was made of the phagocytic activity, representing non-specific immunity, of polymorphonuclear leukocytes from pregnant women . The cells were isolated from heparinized venous human blood of pregnant women of 10 or more weeks' gestation and non-pregnant women (controls), 20-30 years old . The results indicate that the phagocytosis of inert particles (latex beads) does not significantly change in pregnancy . However, the attachment, ingestion and digestion of Candida albicans significantly increased in pregnancy, with the greatest difference from controls being in the second trimester . These findings suggest that the phagocytic activity in pregnant women is enhanced and that this increased non-specific immunity may compensate in part for weakened specific immunity of the maternal host. J Clin Pharm Ther, 1994 Oct, 19(5), 327 - 32 Preservative efficacy in cefuroxime and ceftazidime eye drop formulations; Barnes AR et al.; The efficacy of various common antimicrobial preservatives was tested in eye drop formulations containing the cephalosporin antibiotics cefuroxime and ceftazidime . The British Pharmacopoeia test for the efficacy of antimicrobial preservatives was used and the formulations were challenged with Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans . The survival of organisms was monitored over 14 days . Cefuroxime sodium, 50 mg/ml, was studied in simple aqueous solution, and dissolved in an artificial tear formulation, Sno Tears (Smith and Nephew Pharmaceuticals), which contains benzalkonium chloride 0.004% w/v . Ceftazidime (50 mg/ml) was also studied in these two vehicles and, in addition, in a phenylmercuric acetate solution (0.002% w/v) and chlorhexidine acetate (0.02% w/v) . Cefuroxime and ceftazidime contributed little, in the short-term, towards a microbicidal preservative effect in the unpreserved aqueous formulations, even against organisms for which they were active . Cefuroxime was adequately preserved in a vehicle of Sno Tears, which contains benzalkonium chloride as the antimicrobial preservative . Ceftazidime was less well preserved in this vehicle, but it was superior to phenylmercuric acetate (0.002% w/v) or chlorhexidine acetate (0.02% w/v). Clin Infect Dis, 1994 Oct, 19(4), 687 - 92 Azole-resistant Candida albicans: report of two cases of resistance to fluconazole and review; White A et al.; We report the course of oropharyngeal infection by Candida albicans that was refractory to treatment with fluconazole in two patients infected by the human immunodeficiency virus (HIV) . We also review the epidemiology of C . albicans with decreased in vitro and in vivo susceptibility to azole antifungal agents, the significance of such isolates, the known mechanisms by which C . albicans may become less susceptible to azole antifungal agents, and the efficacy of various treatments for mucosal candidiasis . The occurrence in HIV-infected patients of mucosal candidiasis that is refractory to therapy with fluconazole and is due to C . albicans that demonstrates decreased in vitro susceptibility to fluconazole has been reported since 1990 . Following the release of miconazole and ketoconazole in the late 1970s, C . albicans with decreased in vitro susceptibility to these agents was isolated from patients with chronic mucocutaneous candidiasis who required repeated and prolonged courses of therapy . Subsequently, C . albicans with decreased in vitro-susceptibility to ketoconazole, clotrimazole, and itraconazole has been isolated from HIV-infected patients . Recent reports of the sexual and nosocomial transmission of wild-type C . albicans indicate the possibility of future person-to-person transmission of C . albicans with decreased in vitro susceptibility to azole antifungal agents. Clin Infect Dis, 1994 Oct, 19(4), 684 - 6 Clinically significant mucosal candidiasis resistant to fluconazole treatment in patients with AIDS; Newman SL et al.; Eight cases of severe mucosal candidiasis in patients with AIDS who were taking fluconazole at a dosage of 400-800 mg/d are described . Candida albicans alone or in conjunction with Torulopsis glabrata or Candida stellatoidea was isolated from each patient . In vitro susceptibility testing demonstrated resistance to fluconazole in all eight cases . All tested isolates were susceptible to amphotericin B, and six of eight isolates tested were susceptible to itraconazole . All individuals were severely immunocompromised (CD4 lymphocyte counts: mean, 15/mm3; range, 6-39/mm3) and had been receiving prophylaxis with fluconazole for a mean of only 3 months (range, 1-7 months) . The occurrence of candidal mucositis in patients receiving high doses of fluconazole is a matter of concern that requires further study in regard to the causes, prevention, and treatment of the disease. Indian J Chest Dis Allied Sci, 1994 Oct-Dec, 36(4), 173 - 9 Allergic bronchopulmonary aspergillosis: a retrospective study of 35 cases; Behera D et al.; Clinical profile of 35 patients with allergic bronchopulmonary aspergillosis (ABPA) was analysed . The disease was found to be more frequent among females . Constitutional symptoms, expectoration, increased breathless and poor control of asthma were the main presenting features . Skin reactivity against aspergillin and Candida was positive in 30 and 2 cases, respectively . Precipitating antibodies against Aspergillus species was positive in 28 cases, and against Candida albicans in 2 cases . Sputum grew either Aspergillus or C . albicans or both in 19 patients . Absolute eosinophilia was observed only in one third of cases . Chest skiagram revealed characteristic central/proximal bronchiectasis and/or fleeting shadows in all cases . No specific pattern was observed on spirometry . There was no correlation between the duration of bronchial asthma, sputum culture and serology results . Most patients responded well to steroids . One striking feature of the study was that one third of the cases were misdiagnosed as pulmonary tuberculosis and were treated with antitubercular drugs for varying periods of time . A high index of clinical suspicion with appropriate laboratory tests are required to identify these cases. Arch Oral Biol, 1994 Oct, 39(10), 921 - 3 The effect of antifungal agents on the in vitro susceptibility of Candida albicans to apo-lactoferrin; Nikawa H et al.; The effect of subminimal inhibitory concentrations (MICs) of nystatin, amphotericin B, clotrimazole, miconazole and 5-fluorocytosine on the in vitro susceptibility of Candida albicans to physiological concentrations of apo-lactoferrin was investigated . Pre-exposure of C . albicans in 1:4 and 1:16 MICs of the antifungals resulted in an increased resistance to apo-lactoferrin-mediated cell death . Preincubation of Candida in tunicamycin (an agent that inhibits the synthesis of yeast cell-wall mannoproteins) and subsequent exposure to apo-lactoferrin enhanced the antifungal activity, whilst addition of ergosterol (a yeast cell-wall component) to the assay suspension had no significant effect . These results taken together indicate that apo-lactoferrin, an important component of saliva, interacts with cell-membrane constituents of C . albicans such as mannoproteins, and may modulate the effect of topical antifungal agents commonly prescribed for oral candidoses. Mycopathologia, 1994 Oct, 128(1), 13 - 7 In vitro and in vivo antifungal activities of liposomal amphotericin B, and amphotericin B lipid complex; Mitsutake K et al.; The in vitro and in vivo antifungal activities of liposomal amphotericin B (L-AMPH) and amphotericin B lipid complex (ABLC), which is composed of amphotericin B and the phospholipids dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol, were compared with those of conventional amphotericin B (Fungizone, AMPH) . The acute intravenous toxicity was markedly lower in BALB/c mice; 50% lethal doses (LD50s) were 2.75 mg/kg in AMPH, 32.9 mg/kg in L-AMPH and > 75 mg/kg in ABLC . In vitro antifungal activities against Candida albicans, C . parapsilosis, C . tropicalis, C . glabrata, and C . krusei were evaluated by the agar plate dilution method . The activities were unchanged against C . albicans, but MICs increased more than four fold in 18 of the 20 strains other than C . albicans in L-AMPH and in 9 of the 20 in ABLC . L-AMPH and ABLC were as efficacious as AMPH in the treatment of mice infected with C . albicans, and at a dose of 0.5 and 1.0 mg/kg of body weight, ABLC was more efficacious on survival A ten-times larger dose (10 mg/kg) of L-AMPH and ABLC was administered to mice with 100% survival, suggesting improved tolerability as compared to amphotericin B. J Protein Chem, 1994 Oct, 13(7), 619 - 27 Purification and characterization of fungal and mammalian phosphomannose isomerases; Proudfoot AE et al.; Phosphomannose isomerase (PMI) is essential for the production of yeast cell walls . An inhibitor which inhibits the fungal enzyme without altering the activity of the mammalian enzyme would be a potential fungicidal agent, increasingly important in view of the increasing mortality from visceral mycoses in immunosuppressed patients . We have purified human, porcine, and Candida albicans enzymes 29,000-fold to homogeneity, and characterized their physical properties, as well as their kinetic parameters, inhibition constants, and pH dependences . Surprisingly, in view of the large differences between Pseudomonas aerugenosa and Saccharomyces cerevisiae PMI, the human and C . albicans enzymes are almost identical . We suggest therefore that species-selective inhibition of the fungal rather than mammalian enzyme may require molecules which bind away from the substrate binding pocket of the enzyme. Allergy, 1994 Oct, 49(9), 778 - 81 Atopic asthma caused by Candida albicans acid protease: case reports; Akiyama K et al.; Two cases of atopic asthma caused by acid protease produced by Candida albicans are reported . Both patients had high levels of serum IgE antibodies against the acid protease and showed positive conjunctival and immediate bronchial responses when challenged with the protease . Significant histamine release was detected in both patients when their peripheral leukocytes were challenged with the protease antigen . These findings clearly showed that C . albicans acid protease is the causative allergen of atopic asthma. Immunol Lett, 1994 Oct, 42(3), 139 - 44 Vitronectin interacts with Candida albicans and augments organism attachment to the NR8383 macrophage cell line; Limper AH et al.; Candida albicans is an increasingly important cause of mucocutaneous and bloodstream infections . The potential role of circulating adhesive glycoproteins such as vitronectin (Vn) in host defense against C . albicans is currently unknown . Accordingly, we investigated the binding of plasma-derived Vn with C . albicans strain 36082 . Vn specifically bound to C . albicans in a concentration-dependent fashion . Higher affinity binding sites numbered 9.8 x 10(4) sites per organism, with a dissociation constant, Kd of 3.5 x 10(-7) M . Vn binding with C . albicans was significantly inhibited by heparin, suggesting interaction of the organism with Vn's glycosaminoglycan-binding region . To further determine which molecule(s) on the fungus interacted with Vn, C . albicans components were extracted, separated by SDS and blotted with radiolabeled Vn . These studies revealed that Vn binds to a 30 kDa molecule on C . albicans . Finally, we investigated the role of Vn in promoting interaction of C . albicans with phagocytic cells . Incubation of C . albicans in the presence of Vn significantly increased binding of the organism to cultured NR8383 macrophages compared to incubations performed in the absence of Vn . These data demonstrate that C . albicans interacts with the heparin-binding domain Vn and further suggest that Vn augments organism uptake by phagocytic cells. Sao Paulo Med J, 1994 Oct-Dec, 112(4), 639 - 41 Aspergillary bronchopneumonia: an unusual cause of atelectasis and asphyxia in a leukemic patient; Velloso ED et al.; A 22-year-old man in his first relapse of T-acute lymphoblastic leukemia developed fever and a pulmonary infiltrate after 23 days of granulocytopenia . Although having been under amphotericin B for 10 days, productive purulent cough ensued, with right lobe atelectasis and acute ventilatory failure that resolved after the elimination of a thick gelatinous bronchial plug . Sputum cultures yielded Candida Albicans and Staphylococcus epidermidis, and microscopic examination of the sputum plug disclosed Aspergillus hyphae . The patient died 9 days after, of a disseminated Aspergillus infection, confirmed by necropsy. J Biol Chem, 1994 Sep 16, 269(37), 22945 - 51 Identification of a putative transcription factor in Candida albicans that can complement the mating defect of Saccharomyces cerevisiae ste12 mutants; Malathi K et al.; We have isolated an acid proteinase-related gene, ACPR, from Candida albicans using a partial clone (Ganesan, K., Banerjee, A., and Datta, A . (1991) Infect . Immun . 59, 2972-2977) as a probe . Sequencing of the full-length gene revealed an open reading frame that can encode a protein of 699 amino acids . The deduced NH2-terminal amino acid sequence did not correspond with that determined from the purified secretory acid proteinase; however, the encoded protein is antigenically related to secretory acid proteinase and has a putative active site for acid proteinase . Interestingly, the amino acid sequence of the NH2-terminal 215 residues of Acprp is highly similar to the DNA binding domain of Ste12p of Saccharomyces cerevisiae . Gel retardation experiments showed that this region of Acprp, like Ste12p, could bind to S . cerevisiae pheromone response elements, suggesting that Acprp has a function similar to Ste12p . Chimeric constructs composed of S . cerevisiae STE12 and C . albicans ACPR genes complemented the mating defect of S . cerevisiae a or alpha ste12 mutants . Our results suggest the presence of a signal transduction system in C . albicans similar to that of S . cerevisiae mating pathway. Gene, 1994 Sep 15, 147(1), 119 - 24 Isolation and sequence of the Candida albicans FAS1 gene; Zhao XJ et al.; The gene (FAS1) encoding the beta-subunit of fatty-acid synthase (FAS) of Candida albicans has been isolated and analyzed . The gene was isolated on the basis of homology to the Saccharomyces cerevisiae FAS1 gene . Sequence analysis showed that the gene contained an intron-free open reading frame of 6111 bp encoding a protein of 2037 amino acids (aa) (227 916 Da) . C . albicans FAS1 and its product exhibit a high degree of overall sequence relatedness to their counterparts in S . cerevisiae, with identities of 68 and 63% at the nucleotide (nt) and aa level, respectively . In addition, the beta-subunits of both organisms contain the catalytic domains in an identical sequential order . Northern blots demonstrated that the gene encodes a single mRNA of approx . 6.1 kb, and that changes in transcript levels are not a prerequisite of the yeast-to-hyphal transition . Southern blot analysis of C . albicans chromosomes separated by pulsed-field gel electrophoresis showed that FAS1 resides on chromosome 5. Gene, 1994 Sep 15, 147(1), 115 - 8 Sequence of a dihydrofolate reductase-encoding gene from Candida albicans; Daly S et al.; The nucleotide (nt) sequence of the dihydrofolate reductase (DHFR)-encoding gene (DFR1) of Candida albicans was determined . The gene contains an open reading frame of 576 nt, coding for a protein of 192 amino acid (aa) residues (calculated M(r) 22,222), that is 38.5 and 31% similar to the Saccharomyces cerevisiae and human enzymes, respectively . The first 36 residues, at the N terminus, of the deduced aa sequence are identical to those determined by sequencing of the purified enzyme from C . albicans . Putative transcription start points were also determined . Restriction-fragment-length polymorphism analysis of the DFR1 chromosomal region suggests the presence of a single copy of the gene per haploid genome and shows a limited variability among the different C . albicans strains tested. J Biol Chem, 1994 Sep 2, 269(35), 22039 - 45 The collagen binding domain of fibronectin contains a high affinity binding site for Candida albicans; Negre E et al.; A 30-kDa proteolytic fragment from the gelatin/collagen-binding domain of fibronectin is a potent inhibitor of fibronectin binding to Candida albicans, with a molar inhibition constant equal to that of intact fibronectin . Recombinant and proteolytic fragments from the cell-, the fibrin I-, and the heparin II-binding domains also inhibit fibronectin binding, but are 13-1000-fold less active . In suspension, binding of fibronectin to C . albicans is regulated by growth conditions and is specific, saturable, time-dependent, reversible, and divalent cation-independent . Scatchard plot analyses indicate the presence of high affinity (Kd = 1.3 x 10(-9) M) and low affinity (Kd = 1.2 x 10(-7) M) receptors . Recombinant or proteolytic fragments from four binding domains of fibronectin promote adhesion of C . albicans . A recombinant fragment corresponding to the cell-binding domain but with the sequence Arg-Gly-Asp-Ser deleted promotes C . albicans adhesion and inhibits fibronectin binding to C . albicans with the same activity as the natural sequence . Furthermore, four peptides containing the Arg-Gly-Asp-Val sequence and the peptides CS-1 and Arg-Glu-Asp-Val did not block the binding of fibronectin to C . albicans . Thus, in contrast to the specific binding of soluble fibronectin, recognition of immobilized fibronectin by C . albicans is mediated by several domains of the protein . Interactions with the cell-binding domain are not mediated by the Arg-Gly-Asp or other known recognition sequences as it has been suggested . Binding of fibronectin also did not correlate with C3d binding to the avirulent clones of C . albicans strain H12 or with iC3b binding to variants of the strain 4918. Clin Diagn Lab Immunol, 1994 Sep, 1(5), 556 - 62 Granulocyte colony-stimulating factor does not enhance phagocytosis or microbicidal activity of human mature polymorphonuclear neutrophils in vitro; Shimono N et al.; The direct effects of human granulocyte colony-stimulating factor (hG-CSF) on mature polymorphonuclear neutrophils (PMNs) in vitro were studied with regard to chemotaxis, superoxide production, and phagocytosis and microbicidal activity against the following viable microorganisms: Staphylococcus aureus, serum-resistant Pseudomonas aeruginosa, and Candida albicans . Recombinant hG-CSF (rhG-CSF) acted as a chemoattractant for human PMNs in a dose-dependent manner . The chemotactic response of PMNs to N-formyl-methionyl-leucyl-phenylalanine (FMLP) was not enhanced by rhG-CSF at any of the concentrations used . rhG-CSF did not induce the generation of superoxide by itself . However, rhG-CSF was able to prime human PMNs and to enhance O2- release stimulated by FMLP in a dose-dependent manner . rhg-CSF did not enhance phagocytosis or killing of the three species of microorganisms by normal PMNs . With PMNs obtained from patients who had hematological disorders or solid tumors, no enhancement of the microbicidal activity was observed in most cases . Microbial killing mediated by PMNs depended on the ratio of PMNs to target organisms . We concluded from these facts that the most important effect of rhG-CSF was to increase the number of the peripheral PMNs and not to enhance the functions of mature PMNs. Biochem J, 1994 Sep 1, 302 ( Pt 2), 535 - 8 Novel synthetic antimicrobial peptides effective against methicillin-resistant Staphylococcus aureus; Alvarez-Bravo J et al.; Previously, we identified a core undecapeptide of sapecin B having antimicrobial activity . Based on the structure of this peptide, we systematically synthesized peptides consisting of terminal basic motifs and internal oligo-leucine sequences and examined their antimicrobial activities . Of these peptides, RLKLLLLLRLK-NH2 and KLKLLLLLKLK-NH2 were found to have potent microbicidal activity against Staphylococcus aureus, Escherichia coli, methicillin-resistant S . aureus and Candida albicans in liquid medium . We also synthesized the D-enantiomer of KLKLLLLLKLK-NH2 . This enantiomer was resistant to tryptic digestion and persisted longer in the culture medium, showing greater antimicrobial activity than the original peptide. Int Arch Allergy Immunol, 1994 Sep, 105(1), 32 - 7 Abnormal delayed hypersensitivity response to antigens of Candida albicans in alloxan-diabetic mice; Marquis G et al.; Three antigens of Candida albicans were comparatively evaluated to their ability to elicit delayed hypersensitivity (DH) responses in the mouse footpad test, using alloxan-diabetic and normal mice which were primed with heat-killed C . albicans in complete Freund adjuvant . These antigens were: (1) a preparation of sonically disrupted heat-killed cells; (2) a preparation of soluble cytoplasmic material remaining in the supernatant of a broken-cell suspension centrifuged at 100,000 g; (3) a preparation obtained by extraction of pulverized defatted cells with dilute phenol and sodium bicarbonate in water . After separation by polyacrylamide gel electrophoresis, the major components of soluble cytoplasmic material and dilute phenol extract were identified as a 43-kD protein, and glycoproteins of 21, 27 and 38 kD, respectively . Fifty-eight CD-1 outbred mice, which had received a single intravenous injection of alloxan followed by a 28-day rest period, were randomized with normal littermates to distinct experimental groups . Seven days after sensitization, mice were injected with one of the antigens in the right rear footpad and saline in the left rear footpad and the net specific increase in footpad thickness determined 24 and 48 h later . All three antigens elicited significant responses in sensitized normal mice . The responses of sensitized diabetic mice were clearly inferior to those of sensitized normal mice when heat-killed cells and soluble cytoplasmic material were used . Dilute phenol extract elicited equivalent responses at 24 and 48 h in both primed diabetic and normal mice. J Leukoc Biol, 1994 Sep, 56(3), 318 - 27 HIV infection of monocyte-derived macrophages in vitro reduces phagocytosis of Candida albicans; Crowe SM et al.; HIV-1 infection of peripheral blood monocyte-derived macrophages (MDMs) is unrelated to the level of CD4 expression on the surface of the cell, is associated with considerable donor variability, causes minimal cytopathology, and results in peak viral antigen production after 2 weeks of infection . Phagocytosis of opsonized Candida albicans by MDMs infected in vitro with several strains of HIV was compared with that of uninfected cells from the same donors; the proportion of MDMs containing the fluorescein isothiocyanate-labeled yeast was determined by flow cytometry and phase contrast microscopy . The intracellular localization of C . albicans was confirmed by confocal microscopy . Using paired MDMs from nine donors, 81% of uninfected and 53% of HIV-infected MDMs phagocytosed C . albicans . In addition, the number of yeast per cell was significantly higher in uninfected MDMs than in HIV-infected cells (mean 6.1 versus 2.5) . These findings may partially explain the high incidence of mucocutaneous candidiasis in HIV-infected patients with advanced disease. J Bacteriol, 1994 Sep, 176(18), 5686 - 96 A Saccharomyces cerevisiae mutant with echinocandin-resistant 1,3-beta-D-glucan synthase; Douglas CM et al.; A novel, potent, semisynthetic pneumocandin, L-733,560, was used to isolate a resistant mutant in Saccharomyces cerevisiae . This compound, like other pneumocandins and echinocandins, inhibits 1,3-beta-D-glucan synthase from Candida albicans (F.A . Bouffard, R.A . Zambias, J . F . Dropinski, J.M . Balkovec, M.L . Hammond, G.K . Abruzzo, K.F . Bartizal, J.A . Marrinan, M . B . Kurtz, D.C . McFadden, K.H . Nollstadt, M.A . Powles, and D.M . Schmatz, J . Med . Chem . 37:222-225, 1994) . Glucan synthesis catalyzed by a crude membrane fraction prepared from the S . cerevisiae mutant R560-1C was resistant to inhibition by L-733,560 . The nearly 50-fold increase in the 50% inhibitory concentration against glucan synthase was commensurate with the increase in whole-cell resistance . R560-1C was cross-resistant to other inhibitors of C . albicans 1,3-beta-D-glucan synthase (aculeacin A, dihydropapulacandin, and others) but not to compounds with different modes of action . Genetic analysis revealed that enzyme and whole-cell pneumocandin resistance was due to a single mutant gene, designated etg1-1 (echinocandin target gene 1), which was semidominant in heterozygous diploids . The etg1-1 mutation did not confer enhanced ability to metabolize L-733,560 and had no effect on the membrane-bound enzymes chitin synthase I and squalene synthase . Alkali-soluble beta-glucan synthesized by crude microsomes from R560-1C was indistinguishable from the wild-type product . 1,3-beta-D-Glucan synthase activity from R560-1C was fractionated with NaCl and Tergitol NP-40; reconstitution with fractions from wild-type membranes revealed that drug resistance is associated with the insoluble membrane fraction . We propose that the etg1-1 mutant gene encodes a subunit of the 1,3-beta-D-glucan synthase complex. Clin Exp Immunol, 1994 Sep, 97(3), 347