Allergy, 1993 Aug, 48(6), 394 - 400 Allergens of Pityrosporum ovale and Candida albicans . I . Cross-reactivity of IgE-binding components; Doekes G et al.; In atopic dermatitis (AD), a high prevalence has been reported of type I reactions and specific IgE to extracts of the commensal lipophilic skin yeast Pityrosporum ovale . In the present study, a highly significant correlation (r = 0.77) was found between levels of anti-P . ovale IgE and of IgE reacting with extracts of Candida albicans, both measured by a sensitive ELISA method . In a series of 128 AD sera, 34 sera reacted positively with both yeast extracts, 38 reacted with P . ovale but not with C . albicans, and only one of the 56 anti-P . ovale-negative sera showed a very weak reaction with C . albicans . The correlation was due to a marked cross-reactivity, as shown by inhibition ELISA . Fluid-phase preincubation of double-positive sera with either of the two yeast extracts resulted in a dose-dependent, and at high concentrations complete, inhibition of the IgE reactions with both coated P . ovale and C . albicans allergens . Mutual inhibition of IgE-binding could also be achieved with pools of glycoproteins and/or polysaccharides isolated from the crude extracts by Con A affinity chromatography . P . ovale allergens were, however, more potent fluid-phase inhibitors than the corresponding C . albicans components . The apparently higher avidity for P . ovale allergens suggests that these antiyeast IgE antibodies in AD result from sensitization to P . ovale and cross-react with C . albicans. Mech Ageing Dev, 1993 Aug 1, 70(1-2), 53 - 63 Effect of age and of swimming-induced stress on the phagocytic capacity of peritoneal macrophages from mice; Ortega E et al.; The effect of age and physical activity stress (swimming until exhaustion) on the phagocytic capacity of the peritoneal macrophages was studied in young (12 +/- 4-week-old) and old (68 +/- 6-week-old) BALB/c mice . The attachment and ingestion of opsonized Candida albicans as well as the ingestion of inert particles (latex beads) by these cells was compared between young and old animals at rest . The results show that phagocytosis of peritoneal macrophages is not impaired in old mice . With respect to the effect of physical activity stress, we evaluated the phagocytic capacity both of C . albicans and of latex beads before and immediately after swimming until exhaustion, and in the absence or presence of a previous period (1 month) of training . The results indicate that the phagocytic capacity of peritoneal macrophages is increased after swimming until exhaustion, both with and without previous adaptation or training, and in both young and old mice. Farmaco, 1993 Aug, 48(8), 1103 - 12 Antifungal agents . VI . In vitro antifungal activities of halobenzoyl esters of cis- and trans-{2-(1,1'-biphenyl-4-yl)-2-(1H-imidazol-1-ylmethyl)-1,3- dioxolan-4-yl}carbinols; Stefancich G et al.; The synthesis and the in vitro antifungal activities against Candida albicans and Candida spp of a number of halobenzoyl esters of cis- and trans- {2-(1,1'-biphenyl-4-yl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan -4- yl}carbinols is reported . Some new imidazoles were found more active than ketoconazole and sometimes as potent as bifonazole against Candida albicans . All derivatives were found scarcely active against Candida spp. Ann Rheum Dis, 1993 Aug, 52(8), 570 - 4 Osteoarticular infection in intravenous drug abusers: influence of HIV infection and differences with non drug abusers; Munoz-Fernandez S et al.; OBJECTIVES--To determine (a) the influence of HIV in developing osteoarticular infections in intravenous drug abusers (IVDAs) and (b) the differences between the clinical features of osteoarticular infections in IVDAs and a control group of non-IVDAs . METHODS--A comparative study of the clinical features of osteoarticular infections in all HIV positive and HIV negative IVDAs admitted to the departments of rheumatology and internal medicine during a 10 year period was carried out . The joint infections of all IVDAs, irrespective of HIV status, were compared with those of a control group of non-IVDAs lacking risk factors for HIV infection . RESULTS--A total of 482 HIV positive and 85 HIV negative IVDAs was studied, in whom 25 (5%) and six (7%) osteoarticular infections were found respectively . There were no differences in age, sex, joints affected, and causative agents between these two groups . A comparison of the 31 (5.5%) osteoarticular infections in all IVDAs with 21 infections in 616 (3.4%) non-IVDAs showed significant differences in the mean age (27.5 v 54), the frequency of affection of the axial joints (hip, sacroiliac, and sternocostal joints) (64.5% v 16.6%), and in the incidence of Candida albicans (19% v 0%) . CONCLUSIONS--(1) HIV may not predispose to osteoarticular infections in IVDAs . (2) The hip, sacroiliac, and sternocostal joints (axial joints) were most commonly affected in IVDAs . (3) In Spain, unlike other countries, Gram positive bacteria and C albicans seem to be predominant agents in osteoarticular infections in IVDAs, with a low incidence of Gram negative bacteria. Acta Med Okayama, 1993 Aug, 47(4), 229 - 32 Cell-mediated immunity in bronchial asthma evaluated by purified protein derivative- and Candida albicans-skin reaction; Mitsunobu F et al.; Cell-mediated immunity was examined in 45 patients with bronchial asthma by observing the delayed cutaneous reaction to purified protein derivative (PPD) and Candida albicans (C . albicans) . The delayed skin reaction to PPD showed a decrease with age starting between 50 and 59 years old . The delayed reaction to PPD decreased more prominently with aging, being significantly depressed in the patients aged over 70 years than in those aged between 30 and 49 years (induration, p < 0.02; flare, p < 0.01) . The C . albicans-induced skin reaction was significantly lower in the patients aged over 70 years than in those between 60 and 69 years old (induration, p < 0.01; flare, p < 0.05) . The delayed skin reaction to PPD and C . albicans was significantly depressed in the patients with a serum IgE level over 1001 IU/ml . Delayed skin reaction to PPD and C . albicans was more depressed with aging and an elevated serum IgE, and the age (50-59 years) at the initiation of depression in the PPD-induced delayed skin reaction was younger than that (over 70 years) in the C . albicans-induced reaction. Yeast, 1993 Aug, 9(8), 875 - 87 Cloning and characterization of the SEC18 gene from Candida albicans; Nieto A et al.; The SEC18 gene product is required for protein transport at different stages in the Saccharomyces cerevisiae secretory pathway . The homologous SEC18 gene from Candida albicans has been cloned by complementation of a sec18-1 S . cerevisiae thermosensitive mutant using a C . albicans genomic library in YRp7 . Sequence analysis of the gene revealed a 2382-bp open reading frame which coded for a protein of 88,926 kDa . By an in vitro transcription-translation coupled reaction of the C . albicans SEC18 gene, a protein of approximately 85 kDa was obtained . Hydrophobicity analysis of the protein did not show any predicted signal sequence nor transmembrane anchor domain . These results and the fact that glycosylation was absent in the protein indicated that C . albicans Sec18p did not enter in the secretory pathway . The alignment of the amino acid sequence revealed that the SEC18 gene from C . albicans was homologous to the SEC18 from S . cerevisiae (50% amino acid identity) and to the gene that coded the N-ethylmaleimide-sensitive factor (NSF) protein (43% amino acid identity) . Moreover, the C . albicans Sec18p also showed the putative ATP binding site present in S . cerevisiae Sec18p and in NSF. Clin Exp Allergy, 1993 Aug, 23(8), 689 - 95 Suppressive effects of elimination diets on T cell responses to ovalbumin in hen's egg-sensitive atopic dermatitis patients; Shinoda S et al.; We investigated the effect of elimination diets on T cell responses to ovalbumin (OA) in hen's egg-sensitive atopic dermatitis (AD) patients . The proliferative responses of both peripheral blood mononuclear cells (PBMCs) and T cells with monocytes to OA decreased after elimination diets, but those to Candida albicans or phytohemagglutinin (PHA) did not decrease after elimination diets . The proliferative responses of CD4+ T cells with monocytes to OA decreased after elimination diets . In these patients, clinical symptoms of AD improved . These results indicate that T cells, especially CD4+ T cells, respond to food antigens in food-specific lymphocyte responses, and that elimination diets may be able to initiate reduction of the responsiveness of food-sensitive T cells, especially CD4+ T cells . Moreover, the surface marker phenotypes of the T cells responding to OA were analysed . Our results showed that CD4+CD45RA+ T cells tended to increase . The increase in circulating CD4+CD45RA+ T cells might function as systemic suppression against immune responses in the skin. Cell Immunol, 1993 Aug, 150(1), 36 - 44 Low-dose streptozotocin-induced diabetes in mice . II . Susceptibility to Candida albicans infection correlates with the induction of a biased Th2-like antifungal response; Mencacci A et al.; We have previously found that the development of fatal disseminated candidiasis correlates with the detection of a strong Th2 response, while protective antifungal immunity is associated with a predominant Th1 response . In the present study we verified the hypothesis that an altered antifungal Th response could be responsible for the high susceptibility of diabetic mice to systemic Candida albicans infection . Outbred CD1 mice rendered diabetic with multiple low doses of the pancreatic islet beta-cell toxic, streptozotocin, develop a fatal systemic infection when injected with low-virulence C . albicans cells . Progressive disease was found to be associated with the presence in the serum of IgA, IgE, and IgG1 Candida-reactive specific antibodies, absent footpad reactions, and elevated production in vitro of the Th2 cytokines IL-4, IL-6, and IL-10 but not the Th1 cytokine IFN-gamma . Both the Th2 and Th1 (IL-2 and IFN-gamma) cytokines were produced in vitro by CD4+ lymphocytes from noninfected diabetic mice that, in addition, showed a noticeable footpad reaction to Candida antigens . Thus, it appears that a perturbation in the anticandidal T helper responses resulting in the induction of a biased Th2-like antifungal response renders diabetic mice highly susceptible to systemic C . albicans infection. J Infect Dis, 1993 Aug, 168(2), 502 - 7 Application of biotyping and DNA typing of Candida albicans to the epidemiology of recurrent vulvovaginal candidiasis; Mercure S et al.; One-hundred and five Candida albicans isolates from various anatomic sites of 28 patients, obtained at the onset of two consecutive episodes of well-documented recurrent vulvovaginitis, were typed by methods relying on physiologic or genomic markers . The isolates represented a wide variety of types, and neither a single biotype nor genotype was associated with recurrent vaginitis or a particular body site . Patients generally carried similar strains at various anatomic sites that persisted over time . Genomic methods indicated an 86% rate of relapse, which suggested that most recurrent vaginal infections are of endogenous origin . A similar evaluation with biotyping methods was inconclusive because of a lack of reproducibility, resulting from clonal variation or switching, and difficulties in establishing the number of phenotypic tests necessary to distinguish between identical and different strains . Therefore, Southern hybridization was considered the ideal reference method to study the epidemiology of C . albicans infections. Genitourin Med, 1993 Aug, 69(4), 295 - 6 Is endometrial infection with Candida albicans a cause of recurrent vaginal thrush? Smith JR, Wells C, Jolly M, Shah P, Savage M, Reginald P, Kitchen VS. OBJECTIVE--It was hypothesised that the endometrium might act as a reservoir for candida, thus infecting the vagina as the endometrium is shed during menstruation . DESIGN--A prospective study of women with recurrent vulvo-vaginal candidiasis . The endometrium was sampled and cultured for candida species . SETTING--Central London STD clinic . SUBJECTS--26 women were enrolled, of whom 20 completed the study . RESULTS--One patient had a positive endometrial culture for candida species, the isolate being Candida krusei . CONCLUSIONS--The endometrium is not a common resevoir for candida species and therefore, infection at this site is an unlikely cause of recurrent vaginal candidiasis. Br J Dermatol, 1993 Aug, 129(2), 170 - 4 Amorolfine spray in the treatment of foot mycoses (a dose-finding study); Nolting S et al.; A total of 382 patients with foot mycosis were entered into a dose-finding study . Patients were randomly treated with amorolfine spray 0.5% or 2% (double-blind) or cream 0.5% (open; used as a reference agent) . The spray or cream was applied once daily for 4 weeks on average . At screening, in 348 patients evaluable for efficacy, a total of 381 fungi were isolated: Trichopyton rubrum (196), T . mentagrophytes (73), other dermatophytes (17), Candida albicans (65), other yeasts (23), and moulds (7) . In 33 patients the fungal infection was mixed . Two weeks after the end of treatment, the culture was negative in 94.1% and 97.4% of patients treated with 0.5% or 2% amorolfine spray, respectively . The difference was not statistically significant . In the 0.5% cream group the culture was negative in 86.6% of patients . Nine out of 380 patients evaluable for safety had local adverse events: four (3.2%) in each of the spray groups, and one (0.8%) in the cream group . The most common local adverse events in the patients treated with spray were a burning sensation and dryness of the skin . In conclusion, both spray concentrations were highly efficacious and well tolerated . Further studies should show if more widely spaced treatment with amorolfine spray is as effective as daily administration. FEBS Lett, 1993 Jul 26, 327(2), 231 - 6 Protegrins: leukocyte antimicrobial peptides that combine features of corticostatic defensins and tachyplesins; Kokryakov VN et al.; Porcine leukocytes contained three homologous peptides, PG-1, 2 and 3, that manifested potent microbicidal activity against Escherichia coli, Listeria monocytogenes and Candida albicans in vitro . The peptides ('protegrins') were composed of 16 (PG-2) or 18 amino acid residues, and, like tachyplesins (broad-spectrum antibiotic peptides of horseshoe crab hemocytes), they contained two intramolecular cystine disulfide bonds . Considerably smaller than defensins, protegrins nevertheless showed substantial homology to them, especially to the 'corticostatic' rabbit defensin, NP-3a . The relatively simple structure of protegrins should provide useful prototypes for constructing congeners with selectively enhanced host defense activities. J Med Chem, 1993 Jul 23, 36(15), 2115 - 20 Synthesis and structure-activity relationships of phenyl-substituted benzylamine antimycotics: a novel benzylbenzylamine antifungal agent for systemic treatment; Nussbaumer P et al.; Derivatives of the benzylamine antimycotics with an extra phenyl ring incorporated in the side chain have been prepared and their antifungal activity evaluated . The potency is strongly dependent on the distance between the two phenyl groups and the type of spacer . Linking the aryl rings with a quaternary carbon atom resulted in the identification of highly active compounds 7f and 12a, having a novel 4-benzylbenzylamine side chain . Compound 7f and its 7-benzo{b}thienyl analogue 12a show significantly enhanced efficacy, in particular against Candida albicans, and are among the most potent allyl/benzylamine antimycotics identified so far . Extended investigations with the benzylbenzylamine derivative 7f revealed that, in addition to the enhanced antimycotic profile, the compound is the first representative of the benzylamine antimycotics suitable for systemic treatment. FEMS Microbiol Lett, 1993 Jul 15, 111(1), 63 - 7 Expression of the exoglucanase gene in yeast and hyphal forms of Candida albicans; Chambers RS et al.; The gene for the beta-(1,3) exoglucanase of Candida albicans was used as a probe to detect transcripts of related genes in C . albicans and in several other Candida species . A single homologous transcript was detected in all of the species tested . Expression of the exoglucanase gene in C . albicans was found to be coincident with the onset of growth and the levels of the transcript were proportional to the growth rate . Comparable levels of the transcript were produced during yeast and hyphal forms of growth. FEMS Microbiol Lett, 1993 Jul 15, 111(1), 43 - 7 A kinetic study on the regeneration of Candida albicans protoplasts in the presence of cell wall synthesis inhibitors; Font de Mora J et al.; Aculeacin A and papulacandin B block cell wall regeneration in Candida albicans protoplasts at an intermediate step in which the protoplasts have not yet synthesized the rigid structure of the cell wall and are therefore still osmotically sensitive . In the presence of the antibiotics, total synthesis of glucan is not significantly lowered with respect to control cells, although most of it appears either in the culture medium or in the regenerating wall as alkali-soluble glucan . Thus, it is proposed that echinocandins (such as aculeacin A) and papulacandins may not inhibit glucan synthesis per se but instead inhibit its incorporation into the supramolecular organization of the cell wall. FEMS Microbiol Lett, 1993 Jul 15, 111(1), 101 - 7 Cloning and nucleotide sequence analysis of the Candida albicans enolase gene; Franklyn KM et al.; The complete nucleotide sequence of the coding region as well as the flanking non-coding region of Candida albicans enolase gene was determined . A continuous open reading frame of 1323 nucleotides with no introns was identified . The deduced amino acid sequence showed 87% similarity to the enolases from the yeast Saccharomyces cerevisiae . The two isoforms of enolase are encoded by two non-tandemly arrayed genes in S . cerevisiae . However, DNA hybridisation analysis indicates that in C . albicans enolase is encoded by a single gene . The position of the transcription start site, putative TATA box and polyadenylation signal of the C . albicans enolase gene have been identified . The location of these sequences are similar to those of the S . cerevisiae enolase genes. J Infect Dis, 1993 Jul, 168(1), 195 - 201 Nosocomial acquisition of Candida albicans: an epidemiologic study; Vazquez JA et al.; To evaluate the mechanism and risk factors associated with the nosocomial acquisition of Candida albicans, a 10-month prospective study was conducted in a 24-bed bone marrow transplant unit and an 8-bed medical intensive care unit of a university hospital . A total of 98 patients had samples taken on admission and during hospitalization for culture . Samples from hands of hospital personnel and environmental surfaces were also cultured . C . albicans was isolated from 52 patients, and each patient was matched with a control . Fourteen patients acquired C . albicans after admission to the study . Prior antibiotics and length of time spent in the unit were more common in patients with new acquisition of C . albicans than in controls (92% vs . 64% and 32.5 vs . 13.0 days, respectively) . Restriction enzyme analysis revealed 32 strain types; 4 were common to 30 patients and 10 environmental surfaces . Identical strains of C . albicans from patients who were geographically and temporally associated suggests the exogenous nosocomial acquisition of C . albicans through indirect patient contact. Minerva Ginecol, 1993 Jul-Aug, 45(7-8), 377 - 82 {Fluconazole in the treatment of vaginitis caused by Candida albicans}; Zagni R et al.; The authors verified the local activity and tolerance of the antimycotic drug Fluconazole in 125 cases of women suffering from clinical diagnosed vulvovaginitis caused by Candida albicans . Results were positive with regard to the efficacy and safety of the treatment. Graefes Arch Clin Exp Ophthalmol, 1993 Jul, 231(7), 413 - 5 The effect of the ArF excimer laser on Candida albicans in vitro; Frucht-Pery J et al.; Candida albicans colonies in Sabouraud agar plates were irradiated with the excimer laser as follows: (a) at 10 Hz, power densities of 115-300 mJ/cm2 and 200-3000 pulses, and (b) power density of 115 mJ/cm2 and 200 pulses at 10-50 Hz . Additional colonies were irradiated with a power density of 200 mJ/cm2 at 10 Hz and 500 pulses . Each colony was cultured and the visible colony forming units were counted after 24 h . The cultures remained sterile at: 115 mJ/cm2, 1500 or 3000 pulses; 200 mJ/cm2, 400 or 500 pulses; and 300 mJ/cm2, 300 or 400 pulses . They decreased significantly in other groups . Photoablation with a power density of 115 mJ/cm2 and 200 pulses significantly decreased the number of yeast colonies in the culture plates at 30 Hz (p < 0.029) and 50 Hz (p < 0.02) . Photoablation did not affect the counts in colonies located 1 or 2 mm from the treated colonies . Various energies of the excimer laser may significantly reduce or eliminate yeast in vitro. J Submicrosc Cytol Pathol, 1993 Jul, 25(3), 347 - 55 Muramidase-mediated damage to Candida yeast cells . Histochemical and immunochemical characterization of accumulating wall-like material; Marquis G et al.; Hen egg-white lysozyme is known to be fungicidal to blastoconidia of Candida albicans under defined in vitro conditions . This lethal action leads to changes in the layering of cell wall and to plasmolysis, caused by unremitting accumulation of wall-like material between the yeast cell wall and cytoplasmic membrane . Here, several methods were applied on ultrathin sections to define the nature of wall-like material: histochemical staining with periodic acid-thiocarbohydrazide-silver proteinate, periodic acid-alkaline bismuth, and phosphotungstic acid at low pH; the localization of the carbohydrate residues with lectin-gold complex; immunocytochemical staining with monospecific antibodies, factor 1 and 6, which recognized major cell wall antigens . The wall-like material was almost uniformly highlighted with periodic acid-thiocarbohydrazide-silver proteinate, factor 1 antibody, concanavalin A-gold and wheat germ agglutinin-ovomucoid-gold, indicating the presence of mannoproteins and chitin . The serotype A-specific epitope recognized by factor 6 antibody was not detected in the wall-like material, although it was demonstrated in the outer cell wall layers after 2 h of exposure to lysozyme. J Biomol NMR, 1993 Jul, 3(4), 429 - 41 Heteronuclear NMR studies of 13C-labeled yeast cell wall beta-glucan oligosaccharides; Yu L et al.; The structures of uniformly 13C-labeled beta-glucan octa- and undeca-oligosaccharides enzymatically prepared by the yeast cell wall glucanosyl transferase of Candida albicans were characterized by using a combination of HCCH-COSY, HCCH-TOCSY, and HMBC experiments . The oligosaccharide structures indicate that the cell wall glucanosyl transferase cleaves two glucosyl units from the reducing end of the initial linear beta(1-->3) penta-oligosaccharide and subsequently transfers the remainder to another oligosaccharide at the nonreducing end via a beta(1-->6) linkage . These results indicate that the combined action of cell wall glucanase and glucanosyl transferase activities could not only introduce intrachain beta(1-->6) linkages within a single glucan strand, but also result in cross-linking of two initially separate glucan strands with concurrent introduction of intrachain beta(1-->6) linkages . Since isolated fungal membranes only synthesize linear beta(1-->3) glucan strands, wall-associated enzymes probably participate in the assembly of the final wall glucan structure during cell growth and division. APMIS, 1993 Jul, 101(7), 505 - 16 Enzyme immunohistochemistry with mono- and polyclonal antibodies in the pathological diagnosis of systemic bovine mycoses; Jensen HE et al.; To improve the immunohistopathological diagnosis of systemic bovine mycoses, we have evaluated the utility of antifungal polyclonal and monoclonal antibodies, and peroxidase and alkaline phosphatase staining techniques . A rabbit polyclonal antibody to mannan from Candida albicans was specific for candidosis . The diagnosis of aspergillosis was accomplished using a rat monoclonal antibody to the galactofuran side chains of Aspergillus galactomannan . A murine monoclonal antibody reacting with weakly Con-A binding 41 and 46 kDa somatic antigens from Absidia corymbifera was used for immunostaining of zygomycetic hyphae . Peroxidase antiperoxidase (PAP) and alkaline phosphatase antialkaline phosphatase (APAAP) complexes were visualized using aminoethylcarbazole and fast red substrates . A green staining of PAP reactions with dioctyl sulfosuccinate sodium and 3,3',5,5'-tetramethylbenzidine (DONS/TMB) was effective for the demonstration of fungi in dual and triple infections . Tissue sections of experimentally infected mice were used to determine the sensitivity and specificity of the antibodies . Tissues obtained from 161 bovine mycotic lesions previously studied by indirect immunofluorescence staining were further evaluated using the three antibodies . In all of 45 lesions solely affected by aspergillosis and in three solely affected by candidosis the diagnoses were confirmed by the new evaluation . In 85 of 96 cases of single infections with zygomycetes the diagnosis was confirmed, while none of the antibodies reacted with fungal elements in the remaining 11 lesions . Aspergillus hyphae were detected in all three lesions with dual aspergillosis and zygomycosis, whereas zygomycetic material was confirmed in only two of these cases . A mixed infection of candidosis and zygomycosis in a lymph node was confirmed too . In 13 cases in which a diagnosis had not hitherto been obtained, aspergillosis and zygomycosis were recorded each in three cases. J Infect Dis, 1993 Jul, 168(1), 84 - 91 Phagocytic function of monocyte-derived macrophages is not affected by human immunodeficiency virus type 1 infection; Nottet HS et al.; The immunopathogenesis of human immunodeficiency virus (HIV) infection is characterized by the failure to control opportunistic infections . Here, the direct effect of HIV on macrophage phagocytic function was studied . HIV-1-infected monocyte-derived macrophages expressed as many Fc gamma and complement receptors as did control macrophages . The function of these receptors was not affected by HIV-1 infection since binding and internalization of opsonized Escherichia coli and Staphylococcus aureus were not impaired . Production of reactive oxygen species induced by stimulation of the HIV-1-infected macrophages with opsonized E . coli, zymosan, or PMA was intact . HIV-1-infected macrophages killed opsonized E . coli and Candida albicans as effectively as did control macrophages . These results, therefore, do not support the hypothesis that HIV-1 infection of macrophages causes phagocytic dysfunction and suggest that HIV-induced abnormalities outside the mononuclear phagocyte system may lead to the inability to control opportunistic pathogens. Int J Immunopharmacol, 1993 Jul, 15(5), 605 - 14 Polysaccharides isolated from plant cell cultures of Echinacea purpurea enhance the resistance of immunosuppressed mice against systemic infections with Candida albicans and Listeria monocytogenes; Steinmuller C et al.; Polysaccharides (EP) isolated from large scale plant cell cultures of Echinacea purpurea, have been shown to activate human and murine phagocytes . In this study we investigated the influence of EP on the nonspecific immunity in immunodeficient mice . EP was effective in activating peritoneal macrophages isolated from animals after administration of cyclophosphamide (CP) or cyclosporin A (CsA) . EP-treated macrophages exhibited increased production of tumor necrosis factor-alpha (TNF) and enhanced cytotoxicity against tumor target WEHI 164 as well as against the intracellular parasite Leishmania enrietti . After a CP-mediated reduction of leukocytes in the peripheral blood, the polysaccharides induced an earlier influx of neutrophil granulocytes as compared to PBS-treated controls . EP treatment of mice, immunosuppressed with CP or CsA, restored their resistance against lethal infections with the predominantly macrophage-dependent pathogen Listeria monocytogenes and predominantly granulocyte-dependent Candida albicans . Further, the effects of EP in allogeneic bone marrow chimeric mice are discussed . These findings may have therapeutical implications in prophylactic treatment of opportunistic infections. Arzneimittelforschung, 1993 Jul, 43(7), 782 - 3 Effects of the combination of ketoconazole and calcium channel antagonists against Candida albicans in vitro; Krajewska-Kulak E et al.; Susceptibility of 66 strains of Candida albicans from patients were tested against ketoconazole (Ktz, CAS 65277-42-1), cinnarizine (Cin), verapamil (Ver), nifedipine (Nif), nimodipine (Nim) and the combination of Ktz with these calcium channel antagonists, using Sabouraud's broth . Minimal inhibitory concentrations (MICs) determined on diagnostic plates gave values of Ktz: 34.5 +/- 3.9 micrograms/ml, Cin 413 +/- 11.3 micrograms/ml, Ver 334 +/- 11.4 micrograms/ml, Nif 374 +/- 19.3 micrograms/ml and Nim 486 +/- 20 micrograms/ml . The combination of Ktz and calcium channel antagonists in various ratios (1 : 1, 1 : 2, 2 : 1) was found to exert synergistic effect and the mean values of the combinations were: Ktz+Cin 6.52 +/- 1.67, 6.4 +/- 1.71, 6.06 +/- 1.7 micrograms/ml: Ktz+Ver 11.13 +/- 2.13, 11.63 +/- 2.22, 10.6 +/- 2.1 micrograms/ml: Ktz+Nif 7.37 +/- 1.6, 7.7 +/- 1.57, 7.4 +/- 1.75 micrograms/ml: Ktz+Nim 10.1 +/- 2.28, 10.6 +/- 2.31, 9.91 +/- 2.21 micrograms/ml . These results were significantly different (p < 0.001) compared with ketoconazole . Our findings indicate that some calcium channel antagonists increase the antifungal activity of Ktz against C . albicans in vitro. Arch Oral Biol, 1993 Jul, 38(7), 631 - 4 Interactions between denture lining material, protein pellicles and Candida albicans; Nikawa H et al.; The interactions between pellicles derived from saliva, serum, mucin and lysozyme deposited on lining material (tissue conditioner) and Candida albicans were investigated by monitoring pH changes associated with protein-free and protein-coated lining material and by ultrastructural observations of yeast colonization . No significant differences in pH reduction between culture media in contact with the protein-free, control lining materials and those coated with saliva, serum or mucin were observed after 120 h of incubation . However, scanning electron microscopy revealed that much greater numbers of the yeasts colonized the saliva- or serum-coated lining material than the lysozyme-, mucin-coated or control material . Hyphal invasion was observed in saliva-coated lining material . These results suggested that denture pellicle derived from saliva and/or serum may potentiate candidal colonization of denture lining materials. New Microbiol, 1993 Jul, 16(3), 287 - 91 Relationship between Candida albicans and denture stomatitis: a clinical and microbiological study; Nanetti A et al.; A study was done on 52 upper denture wearers, randomly selected among the residents of two nursing-homes . The results show that the prevalence of Candida albicans in the denture is significantly higher than that in the mucosa . It was also possible to establish a significant relationship between the clinical patterns and the microbiological findings . A healthy mucosa does not present C . albicans, whereas a diffuse denture stomatitis more often presents the yeast both in the mucosa and in the denture . Finally, diffuse erythema is correlated to continuous denture-wearing, while there is not significant correlation between healthy mucosa and type I denture stomatitis and denture-wearing habits. New Microbiol, 1993 Jul, 16(3), 267 - 74 Culture filtrates and whole heat-killed Candida albicans stimulate human monocytes to release interleukin-6; Raponi G et al.; The release of interleukin-6 (IL-6) by human monocytes upon stimulation with culture filtrates and heat-killed Candida albicans cells was studied . Two strains of C . albicans (a wild strain CA3 and an agerminative mutant CA2) were cultured overnight at 28 degrees C in complete medium, and 10(6) cells/ml were either filtered at different time points (6, 12, 18, 24, 30 hours) or heat-killed . C . albicans preparations were then added to monolayers of monocytes isolated from healthy donors and incubated at 37 degrees C in 5% CO2 atmosphere . Cell culture supernatants were collected at different time points (every 6 hrs for 30 hrs), and IL-6 content was then measured by immunometric assay . Monocytes stimulated with heat-killed C . albicans cells released IL-6 in the supernatants with values ranging from 59 to 460 pg/ml, that peaked at 24 hrs of incubation . Using heat-killed whole cells of C . albicans no major differences were observed between the two strains used in their capacity to induce IL-6 . Culture filtrates also stimulated monocytes to release IL-6 and maximal cytokine levels were observed when the monocytes were triggered with filtrates from yeasts cultured for 24 hours . CA2 filtrate induced IL-6 levels to an extent significantly higher than did CA3 filtrate . These data add further evidence to the immunomodulatory properties possessed by structures of C . albicans. Nihon Kyobu Shikkan Gakkai Zasshi, 1993 Jul, 31(7), 908 - 12 {A case of allergic bronchopulmonary candidiasis improved with steroid inhalation}; Iwahashi N et al.; A 49-year-old woman was admitted to hospital because of productive cough and dyspnea . She had been well two months before admission, when she developed an attack of asthma . Chest roentgenogram taken on admission revealed numerous shadows of inhomogeneous density in both lungs . Laboratory findings showed leukocytosis with eosinophilia (25%), high IgE level in serum and positive RAST score to Candida albicans . A diagnosis of allergic bronchopulmonary candidiasis was made by these laboratory data and clinical course . The patient was treated successfully by oral administration of methylprednisolone and inhalation of amphotericin B, but she had a relapse of the disease on cessation of steroid medication . Inhalation of beclomethasone dipropionate and procaterol hydrochloride was commenced . Thereafter, pulmonary infiltration and clinical symptoms improved after three weeks. Am J Respir Cell Mol Biol, 1993 Jul, 9(1), 19 - 25 Mechanism of intracellular candidacidal activity mediated by calcium ionophore in human alveolar macrophages; Vecchiarelli A et al.; In the present study, we investigated the effect of in vitro treatment with calcium ionophore (A23187) on candidacidal activity of human alveolar macrophages (AM) from normal subjects . In vitro incubation of AM with A23187 results in a significant dose-dependent enhancement of candidacidal activity . The availability of Ca2+ and Mg2+ ions in the culture medium is crucial for phagocytosis and killing to occur, but appears irrelevant for the binding between Candida albicans and AM . Enhancement of the killing effect mediated by A23187 does not correlate with increased phagocytic activity; in fact, the availability of ions is required for the phagocytic event, but an increase of cations does not correlate with enhancement of this activity . On the contrary, the augmentation of killing activity correlates with increased production of superoxide anion . Moreover, soluble material endowed with candidacidal activity has been extracted from cytoplasmic granules of AM both unstimulated and following A23187 treatment in vitro . Indeed, the granules extracted contain cationic proteases and, when isolated from stimulated cells, appear to be significantly more cytotoxic for C . albicans with respect to those obtained from unstimulated AM . In conclusion, the results reported here show that the phagocytic and killing events are ion dependent and the enhancement of intracellular candidacidal activity mediated by A23187 in AM is correlated with an augmented anti-Candida activity of cation-activated proteases. Haematologica, 1993 Jul-Aug, 78(4), 249 - 51 Fluconazole prophylaxis and Candida fungemia in neutropenic children with malignancies; Cesaro S et al.; From March, 1990 to February, 1992, we administered fluconazole as antifungal prophylaxis at doses of 3-5 mg/kg/day to 40 patients with prolonged and severe neutropenia following intensive chemotherapy . Fungemia was observed in 3 out 40 patients, and all three of them were due to Candida non-albicans strains: two Candida parapsilosis and one Candida guilliermondi . In vitro sensitivity tests showed that all three isolated strains were susceptible to amphotericin . In one case, Candida guilliermondi was tested for sensitivity to fluconazole and found to be resistant . We conclude that fluconazole prophylaxis proved effective in preventing Candida albicans infections, but it could also contribute to the emergence of Candida non-albicans strains . It might be possible that fluconazole at higher doses could prevent the selection of less susceptible Candida strains. Mycopathologia, 1993 Jul, 123(1), 9 - 17 Treatment of systemic candidiasis in a neutropenic murine model using immunoglobulin G bearing liposomal amphotericin B; Belay T et al.; Efficacy of immunoglobulin G (IgG) bearing liposomal amphotericin B (LAMB-IgG), liposomal amphotericin B without IgG (LAMB) or free amphotericin B (fAMB/Fungizone) was investigated in the treatment of systemic candidiasis in a neutropenic mouse model . Treatment with a single dose (0.6 or 0.9 mg amphotericin B per kg body weight) of LAMB-IgG resulted in a significant increase in the survival rate of neutropenic mice infected with 3 x 10(5) cfu of Candida albicans compared to untreated controls, mice injected with IgG, or liposome alone . Survival was also better in neutropenic mice treated with LAMB-IgG than in neutropenic mice treated with the same dose of LAMB or fAMB . Moreover, 65% of all mice survived the infection after treatment with a single dose of 0.6 mg AMB of the LAMB-IgG formulation . Quantitative culture counts of organs showed that both fAMB and LAMB-IgG formulations even at a dose of 0.3 mg AMB/kg, cleared C . albicans from the spleens, livers, and lungs but not from the kidneys . However, a decreased number of C . albicans cells was recovered from the kidneys of mice that survived the infection . Results of the study suggest that LAMB-IgG is more effective than LAMB or fAMB in the therapy of disseminated candidiasis in neutropenic mice. Mycopathologia, 1993 Jul, 123(1), 19 - 25 Influence of different levels of ammonium concentrations on cell growth, RNA and protein production by Candida albicans; Vidotto V et al.; Candida albicans starved cells were incubated in minimal synthetic liquid media containing different concentrations of ammonium sulphate (0.00, 0.02, 0.05, 0.10, 0.03, 0.50 g/L) . Culture growth was monitored by measuring daily the optical density and by evaluating RNA and protein cellular content after 48 and 96 hours from the inoculum . The environmental availability of ammonium ion influenced the biomass production, that was maximum when its concentration was 0.10 and 0.30 g/L . In addition, an effect on cell duplication time was observed, this was particularly evident when the (NH4)2SO4 concentration was 0.10 g/L . The protein content increased in relation to the increase of ammonium ion availability, with a peak in correspondence to 0.30 g/L and a drop when the greatest concentrations were employed . RNA production was inversely proportional in respect to protein production . The optimal range of ammonium sulphate concentration for C . albicans growth was 0.10-0.30 g/L; over these concentrations there was an inhibitory effect . The rate of the protein and RNA syntheses seems to indicate the growth phase and the nitrogen nutritional conditions of the cultures, respectively. J Antimicrob Chemother, 1993 Jul, 32(1), 123 - 32 In-vitro and in-vivo studies of the decrease of amphotericin B toxicity upon association with a triglyceride-rich emulsion; Souza LC et al.; The effects of amphotericin B associated with a triglyceride-rich emulsion (AB-emulsion), shown previously to behave like lymph chylomicrons, were evaluated in vitro and in vivo . Incorporation of amphotericin B to the emulsion was monitored by UV-visible spectrophotometry . Whilst conventional amphotericin B induced a considerable K+ efflux from erythrocytes, AB-emulsion had essentially no effect . In contrast, the K+ efflux from Candida albicans was similar upon incubation either with AB-emulsion or with conventional amphotericin B . Administration to rats showed reduced mortality due to AB-emulsion compared with conventional amphotericin B . Renal toxicity was also decreased upon AB-emulsion treatment, as evaluated by serum urea and creatinine levels . These data suggest that chylomicron-like emulsions could be utilized as vehicles for amphotericin B in antifungal therapy. Cent Afr J Med, 1993 Jul, 39(7), 140 - 2 Antifungal activity of essential oil from Artemisia afra Jacq; Gundidza M; Artemisia afra is indigenous to the eastern highlands of Zimbabwe where it is used in folk medicine . Hydro-distilled volatile oil from the aerial parts of the plant was tested for antifungal activity against 10 fungal species using the dry weight method . The results obtained showed that the essential oil exhibited significant activity against Aspergillus ochraceus, Candida albicans, Alternaria alternata, Geotrichum candidum, Aspergillus niger, Penicillium citrium and Aspergillus parasiticus. Rev Gastroenterol Mex, 1993 Jul-Sep, 58(3), 225 - 8 {Intestinal lymphoid nodular hyperplasia in a patient with acquired dysgammaglobulinemia, chronic diarrhea, and bacterial overgrowth syndrome}; Castaneda-Romero B et al.; The association between intestinal nodular lymphoid hyperplasia (INLH) and acquired dysgammaglobulinemia was first described by Hermans et al in 1966 . One of the largest series reported in the literature is mexican . We described the clinical out come of a young man with diarrhea, steatorrhea and history of upper respiratory tract infections in whom INLH was established by clinical, radiological, endoscopic and histopathologic studies . Jejunal fluid showed infection by E . coli, C . freundii and Candida albicans as well as cysts of Giardia lamblia . Serum concentration of Ig A and Ig M were decreased . As well as B lymphocytes count in peripheral blood . The patient received treatment with itraconazole, ciprofloxacin and furazolidone with an excellent response . At present he is asymptomatic with cyclic doses of antibiotics and parenteral administration of gammaglobulins. Arzneimittelforschung, 1993 Jul, 43(7), 784 - 8 {Antifungal activity of sulfonated shale oils}; Listemann H et al.; Bituminous shale, developed from marine sediments during the Jura era, is the raw substance for the production of shale oil . The shale oil undergoes heating, distillation, fractionated refining and sulfonation (according to a patented method) resulting in water-soluble sulfonated shale oils (Ichthyol) for medical purposes . The antifungal effect of sulfonated shale oils have been described earlier . In this study an in vitro method is applied which is based upon the CO2 detection as a measure for the sensitivity of fungi to sulfonated shale oils . In addition to the minimal inhibitory concentration values (MIC values), sub-inhibitory concentrations are also determined . The actual efficacy of these antifungal agents is demonstrated via dose-effect curves . Our results show that the fractions of sulfonated shale oils refined at 150 to 210 degrees C (Ichthyol, dark) are fungicidal in concentrations between 0.2 and 16.8% for yeasts, dermatophytes and other hyphomycetes . The fractions of sulfonated shale oils refined at 85 to 150 degrees C (Ichthyol, light), on the other hand, showed a clearly higher antifungal activity (concentrations between 0.1 and 5.9%) for all fungi tested . An extended exposition (24 to 168 h) of Candida albicans to these fractions resulted in a further increase of fungicidal activity . Due to the complex nature of sulfonated shale oils the chemically defined antifungal substance(s) have not yet been identified. J Gen Microbiol, 1993 Jul, 139 ( Pt 7), 1643 - 51 Stimuli that induce production of Candida albicans extracellular aspartyl proteinase; Lerner CG et al.; Several species of the opportunistic fungal pathogen Candida produce an extracellular aspartyl proteinase that may assist the organism to invade and colonize host tissues, evade the host immune response and assimilate nitrogen from proteinaceous sources . Although addition of exogenous proteins, such as bovine serum albumin (BSA), to cultures of C . albicans is known to elicit proteinase production, the precise molecular mechanisms controlling regulation of proteinase induction are unknown . We have examined the ability of a variety of macromolecules to induce proteinase production using a chemically-defined nitrogen-limited growth medium and a rapid, sensitive microtitre fluorescent assay for proteinase activity in culture supernatants . BSA and the extracellular matrix protein collagen induced proteinase production . Homopolymers of both poly-L- and poly-D-glutamate also induced proteinase activity, whereas polyglycine, heparin sulphate and dextran sulphate did not . Thus, molecular recognition of proteinase-inducing stimuli is not highly stereospecific, but apparently requires both main- and side-chain interactions . Peptides 8 or more residues in length generally induced proteinase production while most shorter peptides did not . These data reveal that internalization of small peptides with less than 7 residues by peptide transport was not the inducing signal for proteinase production, since Candida dipeptide and oligopeptide permeases do not efficiently transport peptides of more than 6-7 residues . In addition a tight-binding synthetic inhibitor of Candida proteinase (Ki = 0.17 nM) prevented growth of C . albicans on BSA as a sole nitrogen source by blocking protein degradation . Immunodetection of proteinase in these culture supernatants suggests that fully intact proteins, in addition to peptide fragments of sufficient size, are capable of inducing proteinase production.(ABSTRACT TRUNCATED AT 250 WORDS) New Microbiol, 1993 Jul, 16(3), 259 - 66 Effects of bacillus of Calmette-Guerin, Candida albicans and human recombinant interferon-gamma on RNA metabolism and on in vitro release of tumor necrosis factor-alpha by human monocytes/macrophages; Busolo F et al.; Bacillus of Calmette-Guerin (BCG) was found to be effective in the therapy of superficial bladder cancer, although the mechanisms by which this occurs have not yet been clarified . One hypothesis is related to the ability of monocytes/macrophages (MN/M phi) to release tumor necrosis factor-alpha (TNF-alpha), a monokine with cytotoxic and cytostatic effects against certain tumor cell lines . The present study demonstrates that BCG and C . albicans are both very efficient inducers of TNF-alpha, while they inhibit uridine uptake and incorporation into human MN/M phi RNA . However, unlike C . albicans, BCG is cytotoxic for MN/M phi, as determined by release of labelled leucine from target cells. J Biol Chem, 1993 Jun 5, 268(16), 12055 - 61 Purification, characterization, and cDNA cloning of an antifungal protein from the hemolymph of Sarcophaga peregrina (flesh fly) larvae; Iijima R et al.; An antifungal protein (AFP) was purified from the hemolymph of third instar larvae of Sarcophaga peregrina . This protein repressed the growth of Candida albicans in Sabouraud medium in the presence of nitrofurazone . However, in distilled water or saline, AFP alone killed C . albicans . Significant synergism was detected between AFP and sarcotoxin IA, an antibacterial protein of Sarcophaga . The lethal effect of AFP on C . albicans was greatly enhanced by the presence of a small amount of sarcotoxin IA . AFP was shown to bind to C . albicans and cause leakage of a substance(s) with absorbance at 260 nm from the cells . Analysis of its cDNA showed that AFP is a novel histidine-rich protein consisting of 67 amino acid residues. J Infect Dis, 1993 Jun, 167(6), 1467 - 70 Interferon-gamma protects endothelial cells from damage by Candida albicans; Ibrahim AS et al.; Endothelial cells activated with interferon-gamma (IFN-gamma) have been shown to inhibit the replication of Toxoplasma gondii . To determine if this cytokine protects endothelial cells from damage by Candida albicans, human umbilical vein endothelial cells were pretreated with IFN-gamma and infected with C . albicans; endothelial cell damage was measured by the release of 51Cr . Pretreatment with IFN-gamma decreased the extent of endothelial cell injury caused by C . albicans by up to 100% +/- 8.2% . This diminution of endothelial cell damage was confirmed by scanning electron microscopy . The degree of protection was dependent on the concentration of IFN-gamma, with maximum protection occurring at 13 units/mL . Higher concentrations of IFN-gamma were toxic to the endothelial cells . Pretreating the endothelial cells with this cytokine had no effect on candidal germination and growth, suggesting that IFN-gamma stimulates endothelial cells to become resistant to or inhibit the action of candidal virulence factors. Infect Immun, 1993 Jun, 61(6), 2662 - 9 Isolation of avirulent clones of Candida albicans with reduced ability to recognize the CR2 ligand C3d; Franzke S et al.; Four clones of the yeast Candida albicans, isolated on the basis of their tolerance to clotrimazole, were compared with their parental strains in terms of growth, morphology, virulence, and cell surface complement receptor activity . In a newly described synthetic medium, these clones, designated C1, C2, N, and P, produced germ tubes or pseudohyphae, but no true hyphae, in a pattern which was specific for each strain . The growth of each clone at 37 degrees C, under conditions which favor the filamentous growth form of the organism, was equal to that of the parental strain (H12) . The pathogenicity of each clone was tested in an intravenous mouse model . None of the mice infected with the tolerant clones but all of the mice infected with H12 developed severe renal candidiasis after infection with 1.4 x 10(6) to 2.0 x 10(6) CFU/ml . The number of CFU of each clone from the mouse kidney was reduced about 3 or 4 orders of magnitude in comparison with the wild type . As a correlate, we measured the complement receptor activity (CR2 and CR3) of each clone . The C3 ligands, iC3b and C3d, were conjugated to sheep erythrocytes (E) sensitized with antibody (A) to the erythrocytes (EA) . We found that all tolerant clones showed reduced recognition of C3d-bearing sheep erythrocytes (EAC3d) in rosetting assays . Clone P showed more than an 80% reduction in rosetting of EAC3d in comparison with H12 cells . In contrast, recognition of iC3b (EAiC3b) by each of the clones was similar to that by H12 cells . When dithiothreitol extracts of clone P and H12 were compared by immunoblot, both quantitative and qualitative differences in reactivities were observed with antibodies specific for the Candida C3d receptor and with antiserum from a patient with chronic mucocutaneous candidiasis. Infect Immun, 1993 Jun, 61(6), 2644 - 52 Human submandibular-sublingual saliva promotes adhesion of Candida albicans to polymethylmethacrylate; Edgerton M et al.; The purpose of this study was to identify components of saliva that interact with Candida albicans in solution and that may modulate adhesion to dental acrylic (polymethylmethacrylate {PMMA}) surfaces . Saliva-derived pellicles extracted from C . albicans blastoconidia and hyphal-form cells mixed with fresh human submandibular-sublingual saliva (HSMSL) contained predominantly high- and low-molecular-weight mucins (MG1 and MG2, respectively) . In contrast, few components from fresh human parotid saliva were adsorbed to yeast cells . Coating PMMA beads with HSMSL significantly enhanced (10-fold) adhesion of both growth forms of C . albicans compared with human parotid saliva (2-fold), suggesting a role for mucins in adhesion . HSMSL-enhanced adhesion was completely abolished by preadsorbing HSMSL with either blastoconidia or hyphal-form cells prior to coating PMMA . However, coating PMMA with purified salivary mucins or the addition of mucin to preadsorbed saliva did not enhance or restore adhesion to levels found with fresh HSMSL . Adhesion assays employing guanidine-treated fresh HSMSL showed a complete lack of Candida binding, suggesting that subjecting HSMSL to dissociating conditions may alter a property of salivary mucins crucial for C . albicans adhesion . Protease and glycosidase treatment of yeast cells significantly reduced adhesion to HSMSL-coated PMMA . In addition, preincubation of C . albicans with mannose and galactose inhibited adhesion to HSMSL-coated PMMA . These results suggest that mucins may play a role in C . albicans adhesion to saliva-coated PMMA and that a glycoprotein on the yeast surface may be involved in these events. Infect Immun, 1993 Jun, 61(6), 2578 - 84 Evidence that mannans of Candida albicans are responsible for adherence of yeast forms to spleen and lymph node tissue; Kanbe T et al.; We have described a unique binding system between Candida albicans yeast-form cells and the marginal zone of mouse spleen (16) . The chemical nature of the fungal adhesin(s) involved in this binding phenomenon was examined . A fraction obtained by 2-mercaptoethanol extraction (2-ME extract) of fungal cells caused a dose-response inhibition of yeast cell adherence to splenic marginal zone sites and also to subcapsular and medullary sinuses of mouse popliteal lymph nodes . Latex beads coated with the 2-ME extract showed a pattern of spleen and lymph node tissue binding identical to that observed with yeast cells . The extracted adhesins retained their binding activity in vivo . When 0.5 mg of the 2-ME extract was given intravenously to mice, spleen tissue removed up to 3 h later showed over 80% inhibition of yeast cell binding to the spleen marginal zone, and over 50% inhibition was retained for at least 24 h . The adhesins bound to a concanavalin A affinity column and were eluted by 0.5 M alpha-methyl-D-mannopyranoside, and the eluted adhesins were designated Fr.II . Fr.II was further fractioned by DEAE-Sephacel ion-exchange column chromatography, and one especially active and abundant fraction was designated Fr.IIa . The adhesin moiety appeared to be carbohydrate, because the activity of Fr.IIa was destroyed by 20 mM sodium periodate or by 5 U of alpha-mannosidase, but boiling (30 min) or proteinase K (100 micrograms/ml) treatments had no effect . Chemically, whereas the 2-ME extract contained significant amounts of protein and mannose, Fr.IIa consisted of over 98% mannose and less than 0.5% protein . These data strongly suggest that the mannan portion within a mannoprotein is responsible for the binding of yeast cells to splenic marginal zone and to subcapsular and medullary sinuses of mouse lymph node tissue. Infect Immun, 1993 Jun, 61(6), 2520 - 5 Effect of abrogation of natural killer cell activity on the course of candidiasis induced by intraperitoneal administration and gastrointestinal candidiasis in mice with severe combined immunodeficiency; Greenfield RA et al.; Candida albicans CFU per gram of tissue recovered from livers, spleens, and kidneys of 12 severe combined immunodeficiency (scid) and 12 BALB/c mice 5 days after intraperitoneal (i.p.) administration of 10(7) C . albicans cells were not significantly different . Nine scid mice given normal rabbit serum (NRS) as a control and eight scid mice given anti-asialo-GM1 (alpha-ASGM1) had C . albicans CFU per gram recovered from livers and spleens 1 week after i.p . administration of C . albicans that were not significantly different, despite virtual elimination of natural killer (NK) cell activity in mice treated with alpha-ASGM1 . At 2 weeks after i.p . administration, despite significantly increased NK cell activity in eight infected NRS-treated scid mice and virtual elimination of NK cell activity by alpha-ASGM1 treatment of eight scid mice, C . albicans CFU per gram recovered from livers and kidneys were not significantly different . At 2 weeks after intragastric administration of 2 x 10(6) C . albicans cells, eight NRS- and eight alpha-ASGM1-treated scid mice had identical proportions colonized with C . albicans and similar C . albicans CFU per gram recovered from feces . There was no evidence of hematogenous dissemination in either group . Similar results were seen 1 week after intragastric administration of 10(7) C . albicans cells . We conclude that NK cell activity is increased by i.p . administration of C . albicans in scid mice, but nontheless, abrogation of NK cell activity is not associated with enhanced susceptibility to candidiasis induced by i.p . administration and also is not associated with enhanced susceptibility to gastrointestinal colonization or hematogenous dissemination after intragastric administration of C . albicans. N J Med, 1993 Jun, 90(6), 446 - 8 Pancreatic pseudocyst infected with Candida albicans; Farrer WE et al.; We present a case of a pancreatic pseudocyst secondarily infected with Candida albicans . The authors discuss the risk factors for pseudocyst infection, especially with Candida, diagnostic procedures, and current management including percutaneous catheter drainage. J Clin Invest, 1993 Jun, 91(6), 2596 - 601 Enhancement of macrophage candidacidal activity by interferon-gamma . Increased phagocytosis, killing, and calcium signal mediated by a decreased number of mannose receptors; Marodi L et al.; In contrast to its macrophage-activating capacity, IFN-gamma downregulates expression of the macrophage mannose receptor (MMR), which mediates uptake of Candida and other microorganisms . We found that IFN-gamma induced a concentration-dependent increase in the capacity of human monocyte-derived macrophages to ingest and kill both opsonized and unopsonized Candida albicans and to release superoxide anion upon stimulation with Candida . Mannan or mannosylated albumin inhibited this activated uptake of unopsonized Candida, but glucan did not . Addition of mAb to complement receptor (CR) 3 did not inhibit ingestion; macrophages that lacked CR3 (leukocyte adhesion defect) showed normal upregulation of ingestion by IFN-gamma . The increased candidacidal activity of IFN-gamma-activated macrophages was associated with reduced expression of MMR by a mean of 79% and decreased pinocytic uptake of 125I-mannosylated BSA by 73%; K(uptake) of pinocytosis was not changed . Exposure of resident macrophages to unopsonized Candida did not elicit a transient increase in intracellular free Ca2+ ({Ca2+}i); macrophages activated by IFN-gamma expressed a brisk increase in {Ca2+}i on exposure to Candida . These data suggest that macrophage activation by IFN-gamma can enhance resistance to C . albicans infection in spite of downregulation of the MMR, perhaps through enhanced coupling of the MMR to microbicidal functions. J Electron Microsc (Tokyo), 1993 Jun, 42(3), 147 - 55 Morphological changes of Candida albicans induced by BMY-28864, a highly water-soluble pradimicin derivative; Numata K et al.; The time course of BMY-28864-dependent morphological changes in Candida albicans A9540 was studied by electron microscopy . Scanning electron microscopy revealed that BMY-28864 often induced cell surface deformations such as abnormal swelling and bulging around budding sites and bud scars . The cell membrane damage was visualized by freeze-fracturing technique as deep pit-like invaginations . Transmission electron microscopy with thin-sectioned specimens also demonstrated that BMY-28864 induced cell membrane invaginations together with cell membrane detachment from the cell wall, nuclear membrane fragmentation and mitochondrial aberration . Statistical sequence analysis of the prominent BMY-28864-dependent morphological changes of the yeast cells led to the conclusion that BMY-28864 first attacked the cell membrane and then caused disintegration of other intracytoplasmic organelles, resulting in the lethal effect. Farmaco, 1993 Jun, 48(6), 725 - 36 Antifungal agents . III . Naphthyl and thienyl derivatives of 1H-imidazol-1-yl-4-phenyl-1H-pyrrol-3-ylmethane; Massa S et al.; The in vitro antifungal activities of some naphthyl and thienyl derivatives of 1H-imidazol-1-yl-4-phenyl-1H-pyrrol-3-ylmethane against Candida albicans and Candida spp are reported . The title derivatives were prepared starting from proper arylstirylketones, which were reacted with tosylmethylisocyanide (Tos-MIC) to afford the related 4-phenyl-1H-pyrrol-3-yl aryl ketones . Reduction of ketones to the corresponding carbinols followed by treatment of the last compounds with 1,1'-carbonyldiimidazole (CDI) gave the title imidazoles . The related N-methylpyrrole derivatives are also described. Chem Pharm Bull (Tokyo), 1993 Jun, 41(6), 1043 - 8 Optically active antifungal azoles . II . Synthesis and antifungal activity of polysulfide derivatives of (2R,3R)-2-(2,4-difluorophenyl)-3-mercapto-1-(1H- 1,2,4-triazol-1-yl)-2-butanol; Tasaka A et al.; In an effort to find potent antifungal agents, a variety of optically active triazole derivatives with a polysulfide structure, 3, 4 and 5, were prepared and evaluated for antifungal activity against Candida albicans in vitro and in vivo . The symmetrical polysulfides 3 (m = 2-4) were obtained by an oxidative coupling reaction of (2R,3R)-2-(2,4-difluorophenyl)-3-mercapto-1-(1H-1,2,4-triazol-1-yl )-2-butanol (1) or by the treatment of its thiocarbonate derivative 8 with potassium tert-butoxide . The unsymmetrical disulfides 5 were synthesized by the reaction of the thiol 1 with Bunte salts 11 or the thiosulfinate 12 or by the reaction of the thiocarbonate 8 with various thiols 13 . All of these polysulfides showed potent antifungal activity against candidosis in mice. J Gen Microbiol, 1993 Jun, 139 ( Pt 6), 1195 - 207 Multiple chromosomal and phenotypic changes in spontaneous mutants of Candida albicans; Rustchenko-Bulgac EP et al.; Previous studies have revealed the occurrence of multiple chromosomal alterations among spontaneous colony form mutants and clinical isolates of Candida albicans . In this report we show that such karyotype alterations are also seen in spontaneous and induced non-germinative mutants of the fungus . To determine if phenotypic changes other than colony form and microscopic morphology accompanied the rearrangements of the electrophoretic karyotype, we studied the following characteristics of the non-germinative and some of the colony form mutants: formation of pseudohyphae, chlamydospore production, germ tube formation, colony morphology, auxotrophy, growth at various temperatures, and colony morphology and pigment formation on selected media (bismuth sulphite and Phloxine B) . We established that phenotypic and karyotypic variability among spontaneous, non-germinative mutants was no different than such variability among spontaneous colony form mutants . Thus, non-germination may represent another phenotypic consequence of genomic instability in C . albicans . The variability in different phenotypic attributes that occurred amongst the mutants was not associated with any given karyotype . Moreover, neither the low nor the high phenotypic variabilities observed were explained by the relatively high number of alterations in a limited number of chromosomes. J Gen Microbiol, 1993 Jun, 139 ( Pt 6), 1187 - 93 Induction of extracellular proteinase in Candida albicans; Homma M et al.; Pulse-chase experiments indicated that the extracellular proteinase (EPR) of Candida albicans originates as a 45 kDa precursor protein which is processed to a 43 kDa protein prior to secretion . Secretion was routinely stimulated in EPR induction medium which contains bovine serum albumin (BSA) and glucose . Although EPR was not induced without glucose as a carbon source, EPR secretion was induced without the addition of BSA or other nitrogen sources . Furthermore, it was shown that EPR production was not induced at pH > 6.0, irrespective of the presence of a nitrogen source . This suggests that medium pH may act directly upon EPR induction, and not as a secondary effect of the nitrogen supply from EPR-mediated protein digestion, which exhibited a pH optimum of around pH 3.5 . When germ tube induced cells were transferred to EPR induction medium, EPR was not induced . Thus, EPR production and germ tube formation may not be induced by the same conditions . We speculate that EPR production and germ tube formation do not co-operate in the invasive process but play different and separate roles. J Gen Microbiol, 1993 Jun, 139 ( Pt 6), 1177 - 86 Purification and characterization of the extracellular aspartyl proteinase of Candida albicans: removal of extraneous proteins and cell wall mannoprotein and evidence for lack of glycosylation; Morrison CJ et al.; Aspartyl proteinase (AP) is an extracellular enzyme of Candida albicans implicated as a pathogenic factor . Previous reports on the purification and characterization of AP suggested that a single DEAE-Sephadex chromatographic step was sufficient for the removal of extraneous proteins and that the final product was glycosylated . We purified AP using a chromatographic series consisting of DEAE-Sephadex A25, Sephadex G75 and rechromatography on DEAE-Sephadex A25 . Use of DEAE-Sephadex alone did not remove extraneous proteins and removed little contaminating mannoprotein (MP) . The addition of a Sephadex G75 column to the purification scheme removed the majority of contaminating MP and proteins . The final DEAE-Sephadex A25 chromatographic step resulted in (a) removal of detectable extraneous proteins, (b) removal of immunologically detectable MP by dot blot and Western blot enzyme immunoassay, (c) loss of periodic acid-silver stain positivity, and (d) a high AP yield (1295 U l-1) and specific activity (1749 U mg-1) . We conclude that a single DEAE-Sephadex A25 purification step is insufficient to remove extraneous proteins and MP, which could interfere with the production of AP-specific antibodies and the dissection of moieties responsible for immune reactivity . Reports of periodic acid-Schiff or anthrone positivity of AP preparations may reflect the presence of extraneous MP, which can be removed by the chromatographic series we describe. Immunol Cell Biol, 1993 Jun, 71 ( Pt 3), 221 - 5 Patterns of resistance to Candida albicans in inbred mouse strains; Ashman RB et al.; Candida albicans infections were established in eight inbred strains of mice . Using established histological criteria, only two strains (AKR and CBA/CaH) were found to exhibit severe lesions . The remainder showed only mild tissue damage . Deaths occurred in three strains: CBA/CaH, A/J and DBA/2 . The last two strains lack the important complement component C5 . Colony counts in the brain varied widely between strains and showed no correlation with the extent or severity of tissue destruction . However, strains lacking C5 had a significantly greater fungal burden in the brain than C5-sufficient mice . The data are discussed in relation to concepts of susceptibility and resistance to C . albicans in experimental infections in mice. Cell Mol Biol (Noisy-le-grand), 1993 Jun, 39(4), 377 - 81 Water molecules bound to fibrils by hydrogen bonds play an important role on the surface fibrillar structure of Candida albicans cells; Monodane T et al.; Influence of surrounding media on the appearance of surface structure of Candida albicans was further investigated by rapid-freezing and freeze-fracturing techniques with a scanning electron microscope . Fibrillar structure was observed on the surface of the cells treated with water, chloroform, trichloroethane, toluene or isoamyl alcohol, but not on that of the cells treated with methanol, ethanol, isopropanol, n-butanol, acetic acid or acetone . The appearance of the fibrillar structure is proposed to be discussed in a viewpoint of the chemical interactions among the constituent molecules of a fibril, water molecules bound to the fibril molecules and the molecules of surrounding medium, especially a role of water molecules bound to the fibril molecules by hydrogen bonds. FEMS Microbiol Lett, 1993 Jun 1, 110(1), 121 - 5 Biosynthesis of glycoproteins in Candida albicans: processing of a Man6-GlcNAc2-Asn oligosaccharide by membrane fractions; Flores-Carreon A et al.; When a M6-GlcNAc2-Asn oligosaccharide isolated from ovalbumin was incubated with a membrane fraction from Candida albicans and GDP-{14C}Man only one set of low molecular mass products was obtained, which contained 7, 8, 9 and 10 mannose residues in a ratio of 13:6:3:1, as deduced from fast atomic bombardment mass spectrometry analysis . When a mixture of these products was reincubated with a fresh membrane preparation and cold GDP-Man, no further mannose incorporation was observed, indicating that these compounds are not recognized as substrates by the glycan processing system in this organism . Results are discussed in terms of the early glycan processing steps in C . albicans. J Clin Microbiol, 1993 Jun, 31(6), 1472 - 80 Characterization and partial nucleotide sequence of the DNA fingerprinting probe Ca3 of Candida albicans; Anderson J et al.; The moderately repetitive Ca3 fragment of Candida albicans has been used as an effective DNA fingerprinting probe in epidemiological studies . EcoRI digestion of Ca3 DNA results in seven fragments of 4.2 kb (A), 2.98 kb (B), 2.85 kb (C), 0.77 kb (D1), 0.77 kb (D2), 0.38 kb (E), and 0.30 kb (F) . Five of these EcoRI fragments have been mapped in the 5'-3' order C B D1 A D2 . The intact Ca3 probe and the three largest EcoRI fragments, A, B, and C, were individually used to probe Southern blots of EcoRI-digested DNA of a set of test strains, transverse alternating field electrophoresis-separated chromosomes of strain 3153A, and Northern (RNA) blots of test strain 3153A . Fragments, A, B, and C each generate a different Southern blot hybridization pattern with EcoRI-digested whole-cell DNA; Ca3 sequences are present in at least five of seven separable chromosomes and a minichromosome of strain 3153A; fragments A, B, and C are distributed differently on chromosomes; and fragments A, B, and C do not cross-hybridize . Ca3 hybridizes to three major transcripts of 2.8, 2.3, and 1.5 kb . Fragment A hybridizes intensely to the 1.5-kb transcript, while fragments B and C both hybridize intensely to the 2.8- and 2.3-kb transcripts . The B fragment, which contains 2,980 bp and contributes to the major portion of the Ca3 pattern, was sequenced . Both direct and inverted repeat sequence motifs were identified . These results provide us with initial insights into the evolution of the Ca3 pattern and the nature of the probe. Oral Microbiol Immunol, 1993 Jun, 8(3), 177 - 81 The in vitro lysozyme susceptibility of Candida albicans cultured in carbohydrate-supplemented media; Samaranayake YH et al.; The in vitro lysozyme susceptibility of three oral isolates of Candida albicans cultured in carbohydrate-supplemented media was studied . Lysozyme was shown to have a dose- and time-dependent killing effect on C . albicans isolates . Fungicidal activity persisted to varying degrees when yeast isolates were cultured in a variety of carbohydrates (glucose, galactose, sucrose, maltose, xylitol and lactose) before exposure to 20 micrograms/ml lysozyme . Sucrose and galactose grown yeasts exhibited increased resistance to lysozyme compared with (in decreasing order) those grown in glucose, maltose, xylitol or lactose . Further, the C . albicans isolates tested demonstrated strain variations in their susceptibility to lysozyme . These results suggest that dietary carbohydrate may play a role in modulating the yeast cell populations in the oral cavity by altering the fungal susceptibility to salivary lysozyme. Hum Reprod, 1993 Jun, 8(6), 866 - 9 Spermicidal and antiviral properties of cholic acid: contraceptive efficacy of a new vaginal sponge (Protectaid) containing sodium cholate; Psychoyos A et al.; Cholic acid (sodium cholate) exhibits a strong spermicidal and antiviral {anti-human immunodeficiency virus (HIV)-1} activity . The same effects are observed for F-5 Gel, the active mixture of a new contraceptive sponge (Protectaid), which contains sodium cholate in association with low concentrations (0.5%) of nonoxynol-9 and benzalkonium chloride . Both cholic acid and the F-5 Gel exert a dose-dependent, in-vitro inhibitory effect (i) on the activity of HIV-1 associated reverse transcriptase in an acellular system and (ii) on the potential of HIV-1 efficiently to infect human lymphocytes . During 12 months use, the contraceptive efficacy of the 'Protectaid' sponge was 100% in 20 young women who had chosen this method for reasons of both contraception and anti-sexually transmitted disease . No side-effects were recorded throughout this period . Cervical cultures at 6-month intervals showed the presence of Mycoplasma hominis and Candida albicans in one or two cases . The combined spermicidal and anti-HIV properties of cholic acid reported in this paper and used in the 'Protectaid' sponge offer a new and modern protective method of contraceptionPIP: Cholic acid (sodium cholate) exhibits a strong spermicidal and antiviral {anti-human immunodeficiency virus (HIV)-1} activity . The same effects are observed for F-5 Gel, the active mixture of a new contraceptive sponge (Protectaid), which contains sodium cholate together with low concentrations (0.5%) of nonoxynol-9 and benzalkonium chloride . Both cholic acid and the F-5 Gel exerted a dose-dependent, in-vitro inhibitory effect 1) on the activity of HIV-1 associated reverse transcriptase in an acellular system (their 50% inhibitory dose was 7.2 mM and 0.8 x 10 -3 v/v, respectively, and 2) on the potential of HIV-1 to infect human lymphocytes efficiently . In the 3 semen samples examined, sperm motility was instantaneously inhibited by the addition of a 6 mM solution of sodium cholate or of a 1:10 dilution of F-5 Gel . Both cholic acid and F-5 Gel affected in a dose-dependent manner the viability of normal peripheral blood lymphocytes (NPBL) and CEM cells . The Protectaid contraceptive sponge impregnated with F-5 Gel was given to 20 young women aged 19-25 years for a period of 1 year who had chosen this method for both contraception and against sexually transmitted diseases . All women were instructed to insert the sponge within the 12 hours preceding each sexual intercourse and to remove it 4-6 hours afterwards . During 12 months of use with at least 3 intercourse per week, the contraceptive efficacy of the Protectaid vaginal sponge was 100% . Cervical cultures at 6-month intervals showed the presence of Mycoplasma hominis and Candida albicans in 1 and 2 cases, respectively . The combined spermicidal and anti-HIV properties of cholic acid reported and used in the Protectaid sponge offer a new and modern protective method of contraception . At the end of the study, cervical cultures revealed the presence of Escherichia coli and Candida albicans in 1 case each . No slide effects were recorded, and only 1 woman complained of discomfort . Tidsskr Nor Laegeforen, 1993 May 30, 113(14), 1712 - 5 {Diaper dermatitis . Classification, occurrence, causes, prevention and treatment}; Langoen A et al.; Diaper dermatitis is a multifactorial dermatological disorder characterized by inflammation in the diaper area . About half of all babies and old people in need of care experience light dermatitis, while 20% have moderate and 5% severe dermatitis . Friction from the diaper, occlusion, irritation from faeces, ammonia, detergents, candida albicans, proteolytic and lipolytic enzymes and moisture deposited on the epidermis cause damage at the stratum corneum layer of the epidermis . Diaper dermatitis is caused by a combination of mostly irritant effects . Compounds that infiltrate the skin can aggravate the reaction to the damaged epidermis . The barrier function of epidermis must be restored in order to prevent and treat diaper dermatitis. Gene, 1993 May 15, 127(1), 149 - 50 Sequence of the Candida albicans erg7 gene; Roessner CA et al.; The nucleotide sequence of the Candida albicans erg7 gene, which complements erg7 mutants of Saccharomyces cerevisiae and restores oxidosqualene cyclase activity, was determined . The gene encodes a 728-aa protein that displays homology with squalene-hopene cyclase, providing further evidence that erg7 is the gene encoding 2,3-oxidosqualene cyclase. Arch Intern Med, 1993 May 10, 153(9), 1122 - 4 Fluconazole-resistant Candida albicans after long-term suppressive therapy; Sanguineti A et al.; Candida albicans is generally considered to be susceptible, in vivo, to fluconazole . In the population infected with human immunodeficiency virus, recurrent bouts of oral and esophageal candidiasis have led to increasing use of fluconazole for long-term prophylaxis . With prolonged therapy, the issue of developing resistance emerges . We report a case of fluconazole-resistant C albicans esophagitis that developed after fluconazole was used for more than 600 days. J Biol Chem, 1993 May 5, 268(13), 9206 - 14 Molecular cloning and analysis of the NAG1 cDNA coding for glucosamine-6-phosphate deaminase from Candida albicans; Natarajan K et al.; Candida albicans and other pathogenic Candida species can use N-acetylglucosamine as a sole carbon source for growth . GlcNAc induces the enzymes of GlcNAc catabolic pathway; besides, under certain conditions, GlcNAc also induces a change from the yeast to germ tube morphology . Glucosamine-6-phosphate deaminase (EC 5.3.1.10) is the terminal enzyme of the GlcNAc catabolic pathway . We have purified the deaminase from C . albicans and studied its characteristics . The size of the deaminase estimated from SDS-polyacrylamide gel electrophoresis is 28 kDa . N-Acetylglucosamine 6-phosphate, an allosteric activator of the Escherichia coli deaminase, has no effect on the activity of the C . albicans enzyme . The deaminase is induced over 100-fold by GlcNAc and its level is about 0.3-0.5% of the proteins in crude extract . Three cDNA clones were obtained from a lambda gt11 expression library by immunoscreening with deaminase antiserum . C . albicans genomic DNA blot hybridization revealed that the NAG1 gene, encoding the glucosamine-6-phosphate deaminase, is present in a single copy . Hybrid-selected translation and immunoprecipitation experiments revealed that the purified deaminase and the protein encoded by the clones were similar in size and in their antigenicity . DNA sequencing revealed that the largest cDNA clone contained the complete open reading frame, which can code for a 27.5-kDa protein . The NH2-terminal sequence (35 residues) determined from the purified deaminase was identical to the sequence of the deduced protein . The Nag1 protein has about 47% identity with the sequence of the E . coli glucosamine-6-phosphate deaminase . Furthermore, RNA blot hybridization showed that GlcNAc induces the expression of NAG1 gene. Chemotherapy, 1993 May-Jun, 39(3), 189 - 96 Efficacy of prophylactic and early fluconazole treatment on systemic candidiasis in experimentally neutropenic rabbits; Ozgunes I et al.; The efficacy of prophylactic and early fluconazole treatment on experimental systemic candidiasis was investigated in neuropenic rabbits . Fifteen rabbits were used and divided into three groups: fluconazole was started 24 h before the inoculation of Candida albicans in the first group, and 24 h after the inoculation in the second group . The third group was the control group without antifungal therapy . Prophylactic and early fluconazole treatment for 7 days after C . albicans inoculation did not reduce the mortality and tissue culture positivity in the rabbits significantly . Four of the five rabbits survived 7 days both in the prophylactic and early treatment groups . However, only one rabbit survived for 7 days in the control group . In diagnostic procedures, histopathological examination and evaluation with periodic acid-Schiff stain was found to be the most sensitive . In this study, prophylactic and early fluconazole treatment were found to be insufficient for treatment of systemic candidiasis in neutropenic rabbits. J Clin Microbiol, 1993 May, 31(5), 1354 - 7 Anticandidal activity and interleukin-1 beta and interleukin-6 production by polymorphonuclear leukocytes are preserved in subjects with AIDS; Cassone A et al.; Polymorphonuclear granulocytes (PMN; or neutrophils) from uninfected or human immunodeficiency virus-infected subjects were tested for their ability to inhibit growth of Candida albicans and produce interleukin-1 beta (IL-1 beta) and IL-6 in vitro . It was seen that PMN from AIDS (Centers for Disease Control stage IV) patients expressed equal if not greater anticandidal activity compared with the activity expressed by neutrophils from all other subjects examined . On exposure to granulocyte macrophage-colony-stimulating factor or to a mannoprotein constituent (MP-F2) from C . albicans itself, PMN from AIDS patients showed enhanced antifungal activity and production of remarkable quantities of IL-1 beta and IL-6 . These findings suggest that the functional abilities of PMN to inhibit Candida growth and secrete relevant proinflammatory and immunomodulatory cytokines are intrinsically preserved in AIDS patients. J Biolumin Chemilumin, 1993 May-Jun, 8(3), 159 - 67 Chemiluminescence of mononuclear cells is enhanced during antigen recognition; Tengler RS et al.; Stimulation of phagocytes by several cytokines causes superoxide generation and consequently chemiluminescence . Since antigen-activated lymphocytes generate cytokines, we investigated whether antigen recognition by mononuclear cells, which contain both lymphocytes and monocytes, is accompanied by changes in lucigenin-dependent chemiluminescence . Mononuclear cells which underwent antigen-induced proliferation showed a delayed rise in lucigenin-dependent chemiluminescence in the absence of other stimuli . The common recall antigen Candida albicans increased spontaneous chemiluminescence of mononuclear cells from unselected donors up to 20-fold over control values after 48-72 h of culture . With Rabies virus vaccine as specific antigenic stimulus, only mononuclear cells from rabies immunized individuals responded with enhanced delayed chemiluminescence . In contrast to opsonized zymosan and phorbol myristate acetate, antigens induced no oxidative burst within one hour after addition . Delayed mononuclear cell chemiluminescence was inhibited by the superoxide scavenger superoxide dismutase and by di-phenylene iodonium, a selective inhibitor of the phagocyte NADPH oxidase . A neutralizing monoclonal antibody against interferon-gamma completely abrogated antigen-induced chemiluminescence . Recombinant interferon-gamma by itself induced delayed mononuclear cell chemiluminescence . Thus, antigen-induced delayed mononuclear cell chemiluminescence represents activation of phagocyte NADPH oxidase by interferon-gamma generated by activated lymphocytes. Biochem J, 1993 May 1, 291 ( Pt 3), 765 - 71 Role of maltase in the utilization of sucrose by Candida albicans; Williamson PR et al.; Two isoenzymes of maltase (EC 3.2.1.20) were purified to homogeneity from Candida albicans . Isoenzymes I and II were found to have apparent molecular masses of 63 and 66 kDa on SDS/PAGE with isoelectric points of 5.0 and 4.6 respectively . Both isoenzymes resembled each other in similar N-terminal sequence, specificity for the alpha(1-->4) glycosidic linkage and immune cross-reactivity on Western blots using a maltase II antigen-purified rabbit antibody . Maltase was induced by growth on sucrose whereas beta-fructofuranosidase activity could not be detected under similar conditions . Maltase I and II were shown to be unglycosylated enzymes by neutral sugar assay, and more than 90% of alpha-glucosidase activity was recoverable from spheroplasts . These data, in combination with other results from this laboratory {Geber, Williamson, Rex, Sweeney and Bennett (1992) J . Bacteriol . 174, 6992-6996} showing lack of a plausible leader sequence in genomic or mRNA transcripts, suggest an intracellular localization of the enzyme . To establish further the mechanism of sucrose assimilation by maltase, the existence of a sucrose-inducible H+/sucrose syn-transporter was demonstrated by (1) the kinetics of sucrose-induced {14C}sucrose uptake, (2) recovery of intact {14C}sucrose from ground cells by t.l.c . and (3) transport of 0.83 mol of H+/mol of {14C}sucrose . In total, the above is consistent with a mechanism whereby sucrose is transported into C . albicans to be hydrolysed by an intracellular maltase. J Infect Dis, 1993 May, 167(5), 1247 - 51 Secular trends in the epidemiology of nosocomial fungal infections in the United States, 1980-1990 . National Nosocomial Infections Surveillance System; Beck-Sague C et al.; To identify pathogens causing nosocomial fungal infections and the secular trend in their incidence in US hospitals, data from the National Nosocomial Infections Surveillance System, 1980-1990, were analyzed . During that period, 30,477 fungal infections were reported . The rate rose from 2.0 to 3.8 infections/1000 discharges . The highest number of nosocomial fungal infections/1000 discharges was reported from the burn/trauma service (16.1) . Candida albicans was the most frequently isolated fungal pathogen (59.7%), followed by other Candida species (18.6%) . The rate increased at all four major anatomic sites of infection . Patients with bloodstream infections who had a central intravascular catheter were more likely to have a fungal pathogen isolated than were other patients with bloodstream infection (relative risk = 3.2; P < .001): 29% of fungemia patients and 17% of patients with bloodstream infection due to other pathogens died during hospitalization (P < .001) . Fungi are emerging as important nosocomial pathogens and control efforts should target fungal infections, especially fungemia. J Infect Dis, 1993 May, 167(5), 1168 - 72 Induction of tumor necrosis factor-alpha in murine Candida albicans infection; Allendoerfer R et al.; Candidemia in humans is often associated with an endotoxic shock-like syndrome, comparable to gram-negative sepsis . Tumor necrosis factor-alpha (TNF alpha) has been implicated as a mediator in the endotoxic shock syndrome . The possible role of TNF alpha causing early deaths was explored in a murine model of acute infection with Candida albicans . In vitro data from three mouse strains (BALB/c, C3H/HeJ, and C3H/HeN) and in vivo data from BALB/c mice were obtained . Peritoneal macrophages from all three strains produced TNF alpha in vitro when stimulated with C . albicans . After intravenous infection with 10(8) cfu of C . albicans, mice died within 12 h . TNF concentrations in sera from these mice were significantly greater than in controls . Pretreatment of BALB/c mice with anti-murine TNF alpha did not alter mortality of C . albicans-infected mice, but pretreatment with murine TNF alpha reduced mortality . Therefore, in contrast to what was anticipated, TNF alpha may serve a protective role in murine candidiasis. J Clin Invest, 1993 May, 91(5), 1979 - 86 Mucormycosis during deferoxamine therapy is a siderophore-mediated infection . In vitro and in vivo animal studies; Boelaert JR et al.; This study investigates the pathophysiology of mucormycosis caused by Rhizopus, which has been reported in 46 dialysis patients, while treated with deferoxamine (DFO) . This drug aggravates mucormycosis, which we experimentally induced in guinea pigs and which lead to a shortened animal survival (P < or = 0.01) . The drug's effect on Rhizopus is not mediated through the polymorphonuclear cells . Fe.DFO, the iron chelate of DFO, abolishes the fungistatic effect of serum on Rhizopus and increases the in vitro growth of the fungus (P < or = 0.0001) . This effect is present at Fe.DFO concentrations > or = 0.01 microM, at which fungal uptake of radioiron from 55Fe.DFO is observed . A 1,000-fold higher concentration of iron citrate is required to achieve a similar rate of radioiron uptake and of in vitro growth stimulation as observed with Fe.DFO . These in vitro effects of Fe.DFO (1 microM) in serum on radioiron uptake and on growth stimulation are more striking for Rhizopus than for Aspergillus fumigatus and are practically absent for Candida albicans . For these three fungal species, the rates of radioiron uptake from 55Fe.DFO and of growth stimulation in the presence of Fe.DFO in serum are directly related (r = 0.886) . These results underscore the major role of Fe.DFO in the pathogenesis of DFO-related mucormycosis . Pharmacokinetic changes in uremia lead to a prolonged accumulation of Fe.DFO after DFO administration, which helps explain the increased sensitivity of dialysis patients to DFO-related mucormycosis. Gastroenterology, 1993 May, 104(5), 1532 - 4 Intraluminal pancreatic candidiasis presenting as recurrent pancreatitis; Chung RT et al.; An 88-year-old man with closely spaced attacks of acute pancreatitis who was found to have ductal changes of chronic pancreatitis with multiple noncalcified intraluminal filling defects during endoscopic retrograde pancreatography is presented . These defects proved to be fungus balls made up of Candida albicans . He was treated with longitudinal pancreaticojejunostomy and oral fluconazole and has since remained recurrence free (30 months) . It is suggested that Candida superinfection may occur in a chronically dilated pancreatic duct and may contribute to symptomatic recurrent inflammation of the pancreas. J Bacteriol, 1993 May, 175(9), 2632 - 9 Molecular cloning and characterization of the Candida albicans enolase gene; Mason AB et al.; A DNA clone containing the putative Candida albicans enolase gene (ENO1) was isolated from a genomic DNA library . The sequenced insert contained a continuous open reading frame of 1,320 bp . The predicted 440-amino-acid protein is 78 and 76% identical, respectively, to Saccharomyces cerevisiae enolase proteins 1 and 2 . Only one enolase gene could be detected in C . albicans genomic DNA by Southern analysis with a homologous probe . Northern (RNA) analysis detected a single, abundant C . albicans ENO1 transcript of approximately 1,600 nucleotides . When cells were grown on glucose, levels of ENO1 mRNA were markedly increased by comparison with ENO1 mRNA levels in cells grown on ethanol, a gluconeogenic carbon source . In contrast to this glucose-mediated transcriptional induction, the carbon source had no dramatic effect on the levels of enolase protein or enzyme activity in the C . albicans strains tested . These results suggest that posttranscriptional mechanisms are responsible for modulating expression of the C . albicans enolase gene. Infect Immun, 1993 May, 61(5), 2216 - 9 Lipopolysaccharide restores anti-Candida albicans growth inhibition activity of polymorphonuclear neutrophils from retrovirus-immunosuppressed mice; Yamamoto Y et al.; It has been documented that the immune function of leukocytes may be markedly suppressed after infection of mice with the murine retrovirus Friend leukemia virus (FLV) . Antimicrobial activity of polymorphonuclear neutrophils (PMNs) against Candida albicans is impaired after retrovirus infection of mice, and this occurs as early as 3 days after infection of genetically susceptible BALB/c mice . By 2 weeks after infection, there was essentially very little growth inhibition of C . albicans by PMNs from the FLV-infected mice . However, when bacterial lipopolysaccharide (LPS), a known activator of macrophages and PMNs, was added to PMNs from the FLV-infected mice, anti-C . albicans activity was restored to normal levels . This restoration of anti-C . albicans activity of FLV-infected mouse PMNs was observed after stimulation with as little as 0.01 micrograms of LPS per ml . The data obtained show that the impaired antimicrobial function of PMNs from retrovirus-infected mice can be readily restored by a biological response modifier such as bacterial LPS. Infect Immun, 1993 May, 61(5), 2030 - 6 Heterogeneity of the purified extracellular aspartyl proteinase from Candida albicans: characterization with monoclonal antibodies and N-terminal amino acid sequence analysis; Morrison CJ et al.; Three dominant proteins (41, 48, and 49 kDa) were detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in purified preparations of the extracellular aspartyl proteinase (AP) of Candida albicans . All three proteins bound to the specific carboxyl proteinase ligand, pepstatin A, and were associated with maximum AP activity . The N-terminal amino acid sequence for the 48- and 49-kDa proteins matched that reported by others for AP, whereas the sequence for the 41-kDa protein was unique and was not homologous to any known protein . Time course studies demonstrated the simultaneous presence of all three proteins, supporting evidence that the 41- and 48-kDa proteins were not breakdown products of AP . Previous studies did not detect carbohydrate in SDS-polyacrylamide gels of purified AP preparations stained with periodic acid and silver, making glycosylation an unlikely explanation for the observed differences in the molecular masses of the proteins . Some monoclonal antibodies directed against the 49-kDa protein reacted with the 41- and 48-kDa proteins, indicating cross-reactive epitopes . Other monoclonal antibodies, however, reacted only with the 49-kDa protein . We conclude that three pepstatin A-binding proteins occur in purified AP preparations: two have the same amino acid N terminus as that reported for AP, whereas the third has a unique sequence . All three proteins should be considered when undertaking studies to determine the role of AP in candidal pathogenesis or when preparing specific antibodies for antigen capture assays. Infect Immun, 1993 May, 61(5), 1940 - 9 Analysis of Candida albicans adhesion to salivary mucin; Hoffman MP et al.; Clearance of Candida albicans from the oral cavity is thought to be mediated via specific receptor-ligand interactions between salivary constituents and the fungus . Since surfaces in the oral cavity are normally coated with a saliva-derived pellicle, specific interactions between salivary constituents and C . albicans may also contribute to adhesion of C . albicans to the oral mucosa and dental prostheses . Therefore, the purpose of this study was to identify salivary constituents to which C . albicans is capable of binding . A solid-phase overlay assay was used in which electrophoretically separated rat and human salivary constituents bound to membrane filters were incubated with radiolabelled C . albicans cells . C . albicans adhered to a single salivary component from each host . Correlation of cell-binding activity with specific monoclonal antibody (MAb)-binding activity indicated that the constituent bound by C . albicans in human saliva was low-molecular-weight mucin (MG2) and that in rat saliva was rat submandibular gland (RSMG) mucin . Further studies showed an identical cell hybridization signal and MAb colocalization by using RSMG ductal saliva and an aqueous RSMG extract in the solid-phase overlay assay . Analysis of cell binding to the aqueous extract of RSMG fractionated by anion-exchange chromatography demonstrated that C . albicans binding was restricted to an acidic subfraction of the RSMG extract, which also bound the RSMG mucin-specific MAb . The Candida-binding fraction contained predominantly RSMG mucin glycoprotein and also a noncovalently associated, chloroform-extractable material . Furthermore, we identified two strains of C . albicans which differed severalfold in the ability to bind RSMG mucin in the overlay assay . These results suggest that C . albicans binds to only a specific subfraction of RSMG mucin and that the two C . albicans strains tested differ in the ability to bind RSMG mucin subfractions. Infect Immun, 1993 May, 61(5), 1881 - 8 Immunological activities of a Candida albicans protein which plays an important role in the survival of the microorganism in the host; Tavares D et al.; A protein with an isoelectric point of 4.3 and a relative molecular mass of 43 kDa (p43) was purified from the supernatants of the cultures of pathogenic Candida albicans but could not be detected in the supernatants of cultures of this fungus with pathogenicity previously attenuated after being repeatedly subcultured in vitro . Treatment of BALB/c and C57BL/6 mice with p43 resulted in (i) marked increases in the numbers of splenic immunoglobulin-secreting plaque-forming cells (PFC) with peak responses of immunoglobulin M (IgM) PFC preceding those of IgG PFC, with an isotype restriction pattern of IgG2a > IgG2b > IgG3 > IgG1 > IgM, and (ii) specific immunosuppression of the murine primary immune response against sheep erythrocytes . Immunosuppressive and B-cell mitogenic properties of p43 were quantitatively associated and inversely correlated with susceptibility to C . albicans infection . C57BL/6 mice treated with p43 2 days before inoculation with C . albicans were considerably more susceptible to the fungal infection than untreated mice . The immunobiological and chemical properties of p43 are compared with previously described immunosuppressive and B-cell mitogenic proteins produced by bacteria and viruses, and strategies for immunointervention are discussed. Infect Immun, 1993 May, 61(5), 1823 - 8 Coordinate regulation of two opaque-phase-specific genes during white-opaque switching in Candida albicans; Morrow B et al.; Cells of Candida albicans WO-1 switch spontaneously and frequently between a white and an opaque CFU . Recently, an opaque-phase-specific cDNA, PEP1, was cloned and was demonstrated to code for a pepsinogen . By using a differential hybridization screen, a second opaque-phase-specific cDNA, Op4, has been isolated and its corresponding gene has been cloned . Op4 is coordinately regulated with PEP1 but resides on a different chromosome . During temperature-induced mass conversion from opaque to white, transcription of PEP1 and Op4 is immediately inhibited by the increase in temperature, but transcription of both genes can be rapidly reestablished by a downshift in temperature prior to phenotypic commitment . However, the capacity to rapidly induce both PEP1 and Op4 is lost coincidentally with the second semisynchronous round of cell division and phenotypic commitment during mass conversion . Op4 shows no significant base or amino acid sequence homology with a known gene or protein, respectively . However, the deduced Op4 protein exhibits several interesting characteristics, including a hydrophobic amino terminus with 26 amino acids, a pI of 10.73 for the last 100 amino acids, two serine repeats adjacent to alanine repeats, and the potential for alpha-helical conformation within the alanine-rich sequences . No genomic reorganization was evident in the proximity of Op4 during transcriptional activation and deactivation accompanying the white-opaque transition. Infect Immun, 1993 May, 61(5), 1779 - 85 Increased C3 production in human monocytes after stimulation with Candida albicans is suppressed by granulocyte-macrophage colony-stimulating factor; Hogasen AK et al.; Activation of the complement system is an important part of host resistance against fungal infections . When human monocytes, cultured for 2 days or more, were treated in vitro with Candida albicans for 24 h, an enhancement of their biosynthesis of the complement components C3 and factor B was found . However, when C . albicans was administered to freshly isolated monocytes, a consistent stimulation of factor B biosynthesis occurred, while the C3 production was increased in about 50% of the donors . C . albicans also induced the release of granulocyte-macrophage colony-stimulating factor (GM-CSF) from the cultured cells, apparently in larger amounts in the donors in whom no stimulation of C3 production was found . An antibody to GM-CSF administered with the yeast at the initiation of the monocyte culture caused an increase in the C3 production . Furthermore, when monocytes were treated with recombinant human GM-CSF either at the same time as or 4 days prior to the addition of C . albicans, the increase in C3 production was suppressed or neutralized, while factor B biosynthesis was unaffected . Taken together, these results indicate that monocytes respond to C . albicans with an increased production of complement factors . This may be an important mechanism both for opsonization of the fungus and for initiation of an inflammatory reaction . At an inflammatory site, this complement response may be suppressed by locally produced GM-CSF. Eur J Immunol, 1993 May, 23(5), 1034 - 8 Interleukin-4 and interleukin-10 inhibit nitric oxide-dependent macrophage killing of Candida albicans; Cenci E et al.; Mouse peritoneal and splenic macrophages treated with interferon-gamma (IFN-gamma) and infected with the yeast Candida albicans expressed high fungicidal activity in vitro that correlated with increased nitrite concentrations in culture supernatants . Both effects were reduced by an inhibitor of nitric oxide (NO) synthesis which, in vivo, impaired the animals' ability to mount a footpad reaction and clear the fungus from infected organs . Because T helper type-2 (Th2) cytokines in candidiasis are known to limit the expression of protective Th1 functions, we tested the effect of interleukin (IL)-4 and IL-10 on candidacidal activity and NO production of IFN-gamma-activated macrophages . Fungal killing and NO secretion were inhibited, in a dose-dependent manner, by the two cytokines either separately or in combination . Impaired candidacidal activity was also demonstrable in the presence of monoiodoacetic acid, an inhibitor of phagocytosis . These data demonstrate that NO is involved in macrophage killing of C . albicans and support the notion that regulation of Th1 effector function by IL-4 and IL-10 might involve modulation of NO synthesis. J Surg Res, 1993 May, 54(5), 445 - 50 Splenectomy predisposes to fungal sepsis through defective phagosome formation; McCarthy JE et al.; Postsplenectomy septic sequelae may be fatal, but the mechanisms are unclear . We hypothesized that peritoneal macrophage (PM phi) antimicrobial function is abnormal following splenectomy and that this may predispose to increased mortality from the fungal pathogen Candida albicans . Study 1 (in vivo): female CD-1 mice were randomized into control (C), laparotomy (L), or laparotomy+splenectomy (L + S) and inoculated with C . albicans (10(7) organisms, ip) and were studied for mortality . Study 2 (in vitro): mice were randomized to C, L, or L + S groups . Twenty-four hours later, PM phi were harvested and studied for their antifungal activity, including percentage PM phi ingestion of C . albicans and vacuolar sealing of C . albicans within PM phi, percentage C . albicans killing, and superoxide anion (O2-) generation, the mechanism by which candida are killed . Results showed decreased phagocytosis and killing of C . albicans in the L + S group (P < 0.05 vs C) and reduced vacuolar sealing (P < 0.05 vs C) but significantly higher O2- release compared to that in other groups (P < 0.05) . Mortality in the L + S group from C . albicans sepsis was significantly higher than that in the other groups (60% compared to 20% in the L group and 13% in C, P < 0.02) . This may have resulted from L + S-induced defective phagocytosis of C . albicans and depressed C . albicans killing but increased O2- release in response to candida . This discrepancy between decreased killing and increased O2- may result from increased leakage of O2- from more unsealed vacuoles in the L + S group . Thus, L + S may predispose to candida-induced mortality through defective PM phi intracellular candida killing while enhancing the release of O2- extracellularly from unsealed vacuoles, causing tissue injury. Diabetes Res Clin Pract, 1993 May, 20(2), 139 - 46 Bovine and human NPH insulins as T cell immunogens; Gregory R et al.; The aim of this study was to assess the immunocompetence of T cells from patients with poorly controlled diabetes with respect to Candida albicans antigen and to compare the relative immunogenicity of human insulin, bovine insulin and protamine at the T-cell level during 6 months treatment with human or bovine NPH insulins . T-cell proliferation was measured in vitro in response to C . albicans, bovine and human insulin, bovine and human NPH and protamine in 17 patients with newly-diagnosed type 1 (insulin-dependent) and 12 with poorly-controlled type 2 (non-insulin-dependent diabetes) before and after 0.5, 1, 3 and 6 months of treatment with either bovine or human NPH insulin . The following results were found: Baseline responses to C . albicans (as a recall antigen) were similar for patients and controls despite marked hyperglycaemia in the patients . No patient had a response greater than mean + 2 S.D . of controls to human or bovine insulin before starting treatment, or had insulin autoantibodies . Treatment with human NPH insulin did not induce T-cell responses to human or bovine insulin, but 3/13 (23%) patients treated with bovine NPH responded to bovine and human insulin after 6 months, of whom one responded exclusively to human . In contrast, 6 (46%) bovine and 3 (19%) human NPH-treated patients responded to protamine . It was concluded that there is no evidence of T-cell immunosuppression in poorly-controlled diabetes or of T-cell autoimmunity to insulin in newly-diagnosed type 1 diabetes . Treatment with bovine NPH insulin immunizes T cells to insulin, but human NPH does not.(ABSTRACT TRUNCATED AT 250 WORDS) Med Lav, 1993 May-Jun, 84(3), 243 - 8 {Mucocutaneous candidiasis in exposure to biological agents: a clinical case}; Magnavita N; Candida albicans, an ubiquity yeast, has several properties which allow it colonize and invade host tissues, often resisting eradication . Acid proteinase is the virulence factor . Bacterial proteinases are widely used in the detergent industry and the role of occupational exposure to enzymes in the development of mucocutaneous candidosis warrants investigation . A case of candidosis is reported in a worker employed in a detergent factory in whom there was no evidence of any kind of immunosuppression . The relationship between occupational exposure and illness is analyzed. Indian J Exp Biol, 1993 May, 31(5), 450 - 2 Systemic and gastrointestinal candidiasis of infant mice as model for antifungal therapy; Ponnuvel KM et al.; Systemic and gastrointestinal infection was established in infant (15-19 days old) mice after oral-intragastric challenge with Candida albicans . All survivors retained high levels of organisms in the liver, kidney, spleen, stomach and intestine up to the 24th post infection day . These animals with persistent infections were used to study the efficacy of short term antifungal therapy . Drug treatment was initiated on 13th day for a two week period, treatment with fluconazole was compared with amphotericin B, and 5 fluorocytosine . The results suggest that fluconazole is a useful drug in the treatment of gastrointestinal candidiasis. Allergy Proc, 1993 May-Jun, 14(3), 189 - 93 Murine monoclonal antibodies to glycoprotein antigens of Aspergillus fumigatus show cross-reactivity with other fungi; Kumar A et al.; Six monoclonal antibodies produced against Aspergillus fumigatus were studied for their cross-reactivity against other fungal antigens from related and unrelated organisms . Five of the monoclonal antibodies reacted with glycoprotein antigens as evidenced by their binding to concanavalin A, although one did not react with concanavalin A . The reactivities of the monoclonal antibodies with various antigens were studied by biotin-avidin linked immunosorbent assay and Western blots . The results indicate that two monoclonal antibodies (Asp D1 and Asp C9) react with antigens from aspergilli as well as other fungi including Penicillium notatum and Candida albicans, whereas three of six antibodies (Asp H10, Asp ILB8, and Asp C2B1) react with A . fumigatus antigen only . Hence, these monoclonal antibodies can be used to obtain group specific and species specific antigens for various immunodiagnostic assays. Eur J Clin Microbiol Infect Dis, 1993 May, 12(5), 347 - 9 Detection of antibodies to Candida albicans germ tube as a possible aid in diagnosing systemic candidiasis in bone marrow transplant patients; Villalba R et al.; Indirect immunofluorescence assays to detect antibodies to Candida albicans blastospore and germ tube were performed in sera of 29 bone marrow transplant patients . Antibodies to germ tube were present in the sera of six patients, in four of whom a Candida albicans infection was highly probable, while in the other two patients it was not possible to determine the previous course . No healthy blood donors had these antibodies . On the other hand, detection of antibodies to Candida albicans blastospore showed low specificity in the diagnosis of systemic candidiasis . These preliminary findings suggest that the detection of antibodies to Candida albicans germ tube may be an important aid in the diagnosis of systemic candidiasis in bone marrow transplant patients. J Appl Physiol, 1993 May, 74(5), 2432 - 42 TNF-alpha and cyclooxygenase metabolites do not modulate C . albicans septic shock with disseminated candidiasis; Matuschak GM et al.; We analyzed differences in host regulation of tumor necrosis factor-alpha (TNF-alpha) production and pathophysiological responses in conscious rats after infection with two strains of pathogenic Candida albicans spp . (CA-1 and CA-2) compared with Escherichia coli serotype 055:B5 (EC) . The hypothesis was tested that, in contrast to EC, hypotension, organ injury, and mortality after candidemia are not obligatorily dependent on TNF-alpha or TNF-alpha-induced cyclooxygenase pathway metabolites . Dose, viability, and strain-specific dependencies were established after intravenous 10(6) or 10(9) viable CA, as well as heat-killed (HK) or Formalin-inactivated (FI) CA blastospores, compared with live EC at the 24-h LD25 {10(9) colony-forming units (CFU)} and LD100 (10(10) CFU) . Shock without endotoxemia developed 4-8 h after 10(9) live CA-1 or CA-2 (LD100 at 24 h) with disseminated yeast-mycelial transformation and increased microvascular permeability in multiple organs but not after HK or FI CA-1 . Peak serum TNF-alpha after an LD100 of CA-1 or CA-2 was < 3% of LD25 EC values and was < 1% of peak values during lethal bacteremia . Similar pathogen-specific differences were found in liver- and lung-associated TNF . Production of functionally inactive TNF-alpha during candidemia was excluded by enzyme-linked immunosorbent assay and