J Biol Buccale, 1992 Dec, 20(4), 241 - 5 Susceptibility of Candida albicans to peroxidase-catalyzed oxidation products of thiocyanate, iodide and bromide; Majerus PM et al.; The susceptibility of Candida albicans (ATCC 10231 and wild strains) to hypo(pseudo)halous ions (OSCN-, OBr-, OI-) produced by the lactoperoxidase system was tested . Six strains of Candida albicans were isolated from swabs taken from the mouths of children with orthodontic appliances and selected on Sabouraud-Chloramphenicol-Actidione agar plates . The survival rate of Candida blastospores after a 30 min exposure to lactoperoxidase system ranged from 79 to 105% in the presence of 615 microM thiocyanate, from 56 to 88% in the presence of 345 microM bromide and from 0 to 4% in the presence of 250 microM iodide . Results showed that only OI- could exert a strong inhibiting effect in vitro on Candida albicans at physiological concentrations . Nevertheless, the activity of the hypoiodite generating system in saliva was found to be under the control of thiocyanate concentration. J Dermatol, 1992 Dec, 19(12), 972 - 5 An AIDS patient with atopic dermatitis-like eruption responsive to systemic anti-fungal treatment; Hoashi M et al.; Patients with the acquired immunodeficiency syndrome (AIDS) often develop unusual skin complications . We describe a case of a 58-year-old man with AIDS who had a history of multiple transfusions with anti-hemophilic factor A . He developed papulovesicular and lichenified skin lesions on his head, face, neck and the extensor aspects of his extremities accompanied by severe pruritus . Atopic dermatitis was suspected; however, intensive treatment with a potent topical corticosteroid and a systemic antihistamine failed . In addition to the decreased subset of CD4-positive lymphocytes characteristic of AIDS, this patient showed an elevated level of serum IgE particularly specific for Candida albicans, probably because he had a chronic candidial infection of the digestive tract . Oral administration of anti-fungal agents Diflucan and Fungizone produced almost complete relief from the atopic dermatitis-like skin disease within 2 weeks. Tidsskr Nor Laegeforen, 1992 Nov 20, 112(28), 3548 - 51 {Disseminated fungal infections in neonates--risk factors, treatment and course}; Abrahamsen TG et al.; During 10 1/2 months in 1990/91 eight premature babies and one mature baby with an intra-abdominal disease had disseminated Candida albicans infections . The incidence in premature newborns was 9% (8/92 patients) . Risk factors such as respirator therapy, the use of broad spectrum antibiotics, supplemental parenteral nutrition and central intravascular catheters were frequently seen . Four patients survived the fungal infection . These included three of five babies treated with amphotericin B 0.5 mg/kg/day . Two patients who received fluconazole 3 mg/kg/day died after three days . In one patient the diagnosis was obtained post-mortem, and one patient with possible fungemia survived without therapy . The treatment of these patients depends on optimal fungal cultures and good co-operation between paediatricians and microbiologists. FEMS Microbiol Lett, 1992 Nov 15, 78(1), 37 - 42 Correlation between cell-surface hydrophobicity of Candida albicans and adhesion to buccal epithelial cells; Ener B et al.; Adhesion of four isolates of Candida albicans to buccal epithelial cells was determined after growth of the yeasts in defined medium containing 50 mM glucose or 500 mM galactose as the carbon source . With each isolate, adhesion of galactose-grown yeasts was significantly higher than that of glucose-grown organisms . Yeast cell-surface hydrophobicity was assessed by two methods, a modified hydrocarbon adhesion assay and a more sensitive polystyrene microsphere assay . All four isolates were significantly more hydrophobic after growth on 500 mM galactose than after growth on 50 mM glucose . Overall, a strong positive correlation between adhesion and surface hydrophobicity was observed (r = 0.965) . These results are discussed in relation to the role of yeast-surface hydrophobicity in pathogenesis. Med Clin (Barc), 1992 Nov 7, 99(15), 581 - 3 {Systemic chronic candidiasis following typhlitis caused by Candida albicans}; Bosch F et al.; Typhlitis is an infrequent infectious complication which may appear during a period of intense granulocytopenia, generally in patients with acute leukemia . The most common causal germs are Gram negative bacilli although the importance of Candida sp . as an etiologic agent of this disease is ever more frequent . The case of a 14 years old patient with acute lymphoblastic leukemia who, after chemotherapy treatment, presented typhlitis by Candida albicans followed by chronic systemic candidiasis (CSC) is described . The role that Candida albicans may play in some cases of typhlitis is discussed as is the relation between the appearance of typhlitis and the posterior development of CSC. Gene, 1992 Nov 2, 121(1), 173 - 7 The carboxypeptidase Y-encoding gene from Candida albicans and its transcription during yeast-to-hyphae conversion; Mukhtar M et al.; We have cloned and sequenced the gene (CPY1) encoding the carboxypeptidase Y (CPY) of Candida albicans . The gene contains an open reading frame comprising 542 amino acids (aa) with an M(r) of 61,104 . The aa sequence shows 74% identity to the mature CPY aa sequence from Saccharomyces cerevisiae . The putative pre (signal) and pro sequences at the N terminus of the C . albicans protein, however, show significant divergence from the corresponding prepro sequence of the S . cerevisiae protein . Southern analysis of C . albicans genomic DNA suggested the presence of only one CPY-encoding gene . Northern analysis during yeast-to-hyphae conversion suggested that the CPY1 gene is transiently down-regulated on a transcriptional level during the early events of this developmental switch. J Antimicrob Chemother, 1992 Nov, 30(5), 685 - 91 Co-trimoxazole impairs colonization resistance in healthy volunteers; Vollaard EJ et al.; The influence of co-trimoxazole on colonization resistance of the bowel was investigated in six healthy volunteers, by measuring the numbers of indigenous aerobic flora and of a co-trimoxazole resistant challenge strain of Klebsiella pneumoniae . Impairment of colonization resistance of the bowel was shown by a significant increase in the numbers of yeasts in the faeces of five of six volunteers, by a significant increase in the numbers of Gram-negative bacilli in the faeces of two of six volunteers, and by facilitation of colonization of the bowel by the challenge strain in all volunteers . Impairment of colonization resistance of the mouth was shown by the development of glossitis caused by Candida albicans in two volunteers, and by a significant increase in the numbers of yeasts in mouth washings from four volunteers . It is concluded that co-trimoxazole impairs colonization resistance of the gastro-intestinal tract. Arzneimittelforschung, 1992 Nov, 42(11), 1368 - 71 Effects of subinhibitory concentrations of ciclopirox on the adherence of Candida albicans to human buccal and vaginal epithelial cells; Braga PC et al.; At present, only a limited number of studies of the effects of sub-inhibitory antifungal agents on the adherence of Candida to epithelial (buccal and vaginal) host cells are available . The adherence of Candida albicans to the epithelial cell surface is accepted as an important first step in persistent colonization and in the following symptomatic or asymptomatic infection of mucosal surface . Ciclopirox (ciclopiroxolamine, CAS 29342-05-0) is a substituted pyridone antimycotic drug, unrelated to the imidazole derivatives and its topical application ensures maximum local bioavailability . The present study was done to investigate the effects of sub-inhibitory concentrations of ciclopirox on the adherence of Candida albicans to human buccal and vaginal epithelial cells . The findings on the adherence of different strains of Candida indicate that the drug caused a significant reduction in the mean number of Candida adhering to both buccal and vaginal cells . This reduction was maximal at concentration of 1/2 MIC and still significant at 1/4, 1/8, 1/16 MIC, but with progressive return to mean control values at 1/32 MIC . Ciclopirox acts on fungi by inhibiting the intracellular uptake of essential substrates and ions and this probably acts on the Candida ability to express its adherence mechanisms. Arzneimittelforschung, 1992 Nov, 42(11), 1363 - 7 Chronic toxicity study on a new glucan extracted from Candida albicans in rats; Feletti F et al.; Fifty-two-week oral toxicity of a new glucan (Glucanil, Gluimmun) extracted from Candida albicans ATCC 20955 was investigated in rats . The glucan was orally administered in dose levels up to 200 mg/kg/d and was well tolerated . No deviation from normality was observed in mortality, physical appearance and general behaviour of the treated animals . Food and water consumption and body weight gain of glucan-fed groups did not differ from those of control animals . In these groups no alteration of the weight of the main organs was also observed . Hematology, blood chemistry, urinalysis and autopsy findings were within normal ranges in every group of rats treated . No sex difference was noted . In the 200 mg/kg group soft stools or diarrhoea and cecal enlargement with variable hyperplasia of the colon mucosa were observed . These symptoms are typical of exposure to substances which are absorbed incompletely in the small intestine and subjected to microbial metabolism in the cecum and colon . Diarrhoea, cecal enlargement and mucosal hyperplasia are reversible . The no-effect dose level was estimated to be 100 mg/kg/d under these conditions. Enferm Infecc Microbiol Clin, 1992 Nov, 10(9), 520 - 4 {Nosocomial fungemia caused by Candida parapsilosis}; Herrero JA et al.; We review 27 episodes of nosocomial fungemia due to Candida parapsilosis over a 6 year period, compared to a control group of 27 episodes of nosocomial fungemia due to Candida albicans . During the study period, C . parapsilosis accounts for 23% of all yeast isolated from blood-cultures . Fungemia due to C . parapsilosis was more frequently seen in males (23/4) . More than half of the cases (15/27) presented in the postoperative period . In 89% of cases the patients were under total parenteral nutrition and 81% had received broad-spectrum antibiotics . In 41% of cases, the source of the fungemia was unknown, and in another 41% of cases was related to an iv line infection . Direct attributable mortality to C . parapsilosis infection was 11% . When compared to the control group, nosocomial fungemia due to C . parapsilosis occurs in patient with more prolonged courses of total parenteral nutrition, and also was related with less frequent development of septic shock and lower attributable mortality. Clin Exp Dermatol, 1992 Nov, 17(6), 397 - 401 Once-weekly oral doses of fluconazole 150 mg in the treatment of tinea corporis/cruris and cutaneous candidiasis; Suchil P et al.; Ninety-five adult out-patients with tinea corporis and/or tinea cruris participated in a multicentre open non-comparative study investigating the safety and efficacy of 1-4 once-weekly doses of oral fluconazole 150 mg . Trichophyton rubrum was isolated most frequently (67 of 86 mycologically evaluable patients) . A mean of 2.6 doses of fluconazole was administered; patients infected with Candida albicans or Epidermophyton floccosum required an average of 2 doses compared to 3-4 doses in patients infected with other organisms . Clinical cure was obtained in 85 of 92 (92%) patients at the last post-treatment evaluation, with the remaining seven patients being substantially improved . At long-term follow-up, 28-30 days after the last dose, 80 of 91 (88%) patients were assessed as clinically cured, three (3%) patients were improved and eight (9%) patients failed . Among the long-term clinical failures, there was one diagnosis of tinea corporis (3% failure rate) and seven diagnoses of tinea cruris (12% failure rate) . Mycological evidence of infection occurred in only 1 of 86 patients assessed at the last post-treatment follow-up . Mycological relapse occurred in nine (11%) patients at long-term follow-up; one patient was infected with Trichophyton mentagrophytes and eight patients were infected with T . rubrum . Relapse occurred in 2 of 29 (7%) patients with tinea corporis and eight of 57 (14%) patients with tinea cruris (one patient who relapsed had both tinea corporis and cruris) . There was no correlation between the number of doses received and the mycological response or relapse rates at long-term follow-up.(ABSTRACT TRUNCATED AT 250 WORDS) J Gen Microbiol, 1992 Nov, 138 ( Pt 11), 2353 - 62 Toxicity of oxalysine and oxalysine-containing peptides against Candida albicans: regulation of peptide transport by amino acids; Basrai MA et al.; A lysine antimetabolite, L-4-oxalysine {H2NCH2CH2OCH2CH(NH2)COOH}, and oxalysine-containing di-, tri-, tetra- and pentapeptides inhibited growth of Candida albicans H317 . Micromolar amounts of amino acids were found to overcome ammonium repression of the di- and tripeptide transport system(s) in strain H317 . Several amino acids increased the toxicity of oxalysine-containing di- and tripeptides for C . albicans with little or no increase in toxicity of oxalysine or oxalysine-containing tetra- and pentapeptides . L-Lysine completely reversed the toxicity of oxalysine by competing with the transport of oxalysine into the cells . In contrast, L-lysine increased the toxicity of oxalysine-containing di- and tripeptides, but had no effect on the toxicity of oxalysine-containing tetra- and pentapeptides . Incubation of cells with L-lysine for 4 h resulted in a 15-fold increase in the rate of transport of radiolabelled dileucine, indicating that increased sensitivity of C . albicans to some toxic peptides in the presence of L-lysine may be attributed to an increased rate of transport of these peptides . Our results indicate that the dipeptide and tripeptide transport system(s) of C . albicans are regulated by micromolar amounts of amino acids in a similar fashion to the regulation of peptide transport in Saccharomyces cerevisiae and that multiple peptide transport systems differentially regulated by various nitrogen sources and amino acids exist in C . albicans. Cell Mol Biol (Noisy-le-grand), 1992 Nov, 38(7), 799 - 802 Cassia alata and the preclinical search for therapeutic agents for the treatment of opportunistic infections in AIDS patients; Crockett CO et al.; In our search for therapeutic agents from natural sources with potential for the treatment of opportunistic infections in patients afflicted with acquired immunodeficiency syndrome (AIDS), we investigated antibacterial and antifungal activities of water extracts of Cassia alata (C . alata) . The extracts are traditionally used in Ivory Coast, West Africa to treat bacterial infections caused by Escherichia coli (E . coli), and fungal infections caused by Candida albicans (C . albicans) and dermatophytes . Our working hypothesis was that the extract contains active ingredient(s) which can be isolated, identified and developed into useful antibacterial/antifungal agents for the treatment of opportunistic infections in patients with AIDS . We used the broth dilution and agar dilution methods . Specifically, we focused on E . coli and C . albicans and the effectiveness of the extracts was evaluated relative to those of standard antibacterial agent chloramphenicol and antifungal agent amphotericin B . The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) for the water extract of C . alata against E . coli were 1.6 mg/ml and 60 mg/ml, respectively; corresponding data for chloramphenicol were 2 micrograms/ml and 10 micrograms/ml . Similarly, the MIC and minimum fungicidal concentration (MFC) for the extract against C . albicans were 0.39 mg/ml and 60 mg/ml in contrast to 0.58 micrograms/ml and 0.98 micrograms/ml for amphotericin B . From the dose-response curve plots, the extract had an IC50 of 31 mg/ml for E . coli and 28 mg/ml for C . albicans . The data suggest that C . alata extracts contain agent(s) which have therapeutic potential and might be useful if isolated and developed for the treatment of opportunistic infections of AIDS patients. APMIS, 1992 Nov, 100(11), 967 - 75 Influence of muramyl dipeptide on renal candidiasis in genetically distinct mice; Marquis GA et al.; Susceptible (DBA/2) and resistant (C57BL/6) mice were inoculated intravenously with Candida albicans to evaluate the effect of a four-day prophylaxis with muramyl dipeptide (MDP) on the renal burden of organisms during the first week after infection . In sham-treated DBA/2 mice injected with 8 x 10(4) candida cells, renal CFU (LOG10 +/- SEM) on days 1, 4 and 7 after infection were found to average 5.050 +/- 0.109, 4.882 +/- 0.133 and 5.482 +/- 0.245 . In sham-treated C57BL/6 mice injected with 2 x 10(5) candida cells, renal CFU on days 1, 4 and 7 reached only 3.610 +/- 0.118, 3.404 +/- 0.107 and 4.176 +/- 0.580 . MDP-treated DBA/2 mice achieved significant reduction in CFU of C . albicans on day 1 (1.3 log units) and day 4 (0.6 log unit), while MDP-treated C57BL/6 mice had significant reduction in CFU of C . albicans only on day 1 (0.6 log unit) after infection . Sham-treated mice of both strains had a 28.6 to 30% increase in kidney weights on day 4 only, a transient change not seen in MDP-treated mice . Histopathological examination on days 8, 15 and 21 after infection revealed a higher incidence of renal papillary necrosis in DBA/2 mice than C57BL/6 mice (approximately 70% vs 10%) . The incidence of granulomas and of chronic interstitial inflammation was much higher in MDP-treated mice . We conclude that the genetic makeup of the host influences the potential effectiveness of MDP as a biological response modifier. J Antibiot (Tokyo), 1992 Nov, 45(11), 1778 - 84 Enhancement by ubenimex (bestatin) of host resistance to Candida albicans infection; Aoyagi K et al.; Ubenimex is a low molecular weight microbial metabolite which has been demonstrated to have antitumor and immunomodulatory activities . In this study, the protective effect of ubenimex on Candida albicans infection was investigated in normal and immunosuppressed mice . In normal mice, treatment with ubenimex at 0.5, 5 and 25 mg/kg for 5 days prior to infection prolonged survival time in a dose-dependent manner . In immunosuppressed mice treated with a single dose of cyclophosphamide 4 days prior to infection, ubenimex treatment at 5 mg/kg for 5 days significantly increased the number of survivors . Ubenimex-treated mice had a significant increase in number of peritoneal exudate cells with neutrophils as well as enhanced functions, including phagocytosis and active oxygen production . These results suggest the potential usefulness of ubenimex as a prophylactic agent for the management of patients with opportunistic fungal infections. Mol Gen Genet, 1992 Nov, 235(2-3), 453 - 7 Cloning and expression of Candida albicans ADE2 and proteinase genes on a replicative plasmid in C . albicans and in Saccharomyces cerevisiae; Cannon RD et al.; A plasmid vector (denoted pRC2312) was constructed, which replicates autonomously in Escherichia coli, Saccharomyces cerevisiae and Candida albicans . It contains LEU2, URA3 and an autonomously replicating sequence (ARS) from C . albicans for selection and replication in yeasts, and bla (ampicillin resistance) and ori for selection and replication in E . coli . S . cerevisiae AH22 (Leu-) was transformed by pRC2312 to Leu+ at a frequency of 1.41 x 10(5) colonies per microgram DNA . Transformation of C . albicans SGY-243 (Ura-) to Ura+ with pRC2312 resulted in smaller transformant colonies at a frequency of 5.42 x 10(3) per microgram DNA where the plasmid replicated autonomously in transformed cells, and larger transformant colonies at a frequency of 32 per microgram DNA, in which plasmid integrated into the genome . Plasmid copy number in yeasts was determined by a DNA hybridization method and was estimated to be 15 +/- 3 per haploid genome in S . cerevisiae and 2-3 per genome in C . albicans replicative transformants . Multiple tandem integration occurred in integrative transformants and copy number of the integrated sequence was estimated to be 7-12 per diploid genome . The C . albicans ADE2 gene was ligated into plasmid pRC2312 and the construct transformed Ade- strains of both C . albicans and S . cerevisiae to Ade+ . The vector pRC2312 was also used to clone a fragment of C . albicans genomic DNA containing an aspartic proteinase gene . C . albicans transformants harboring this plasmid showed a two-fold increase in aspartic proteinase activity . However S . cerevisiae transformants showed no such increase in proteinase activity, suggesting the gene was not expressed in S . cerevisiae. Am J Physiol, 1992 Nov, 263(5 Pt 1), L526 - 35 Differential systemic and intrapulmonary TNF-alpha production in Candida sepsis during immunosuppression; Lechner AJ et al.; Candida albicans (CA) increasingly causes septic shock, acute lung injury, and multiple organ damage during immunosuppression-related neutropenia . However, the effects of neutrophil (PMN) depletion on induction of tumor necrosis factor-alpha (TNF) by CA and its potential mediation of Candida septic shock are unknown . We hypothesized that reduced CA uptake by circulating PMNs during cyclophosphamide (CY)-related neutropenia sensitizes to TNF-mediated shock from enhanced cytokine production after phagocytosis by tissue macrophages . Absolute or relative neutropenia (PMNs < or = 500/microliters or 2,500/microliters) was modeled in rats by intraperitoneal CY 4-8 days before 10(9) yeast-phase CA (acute studies < or = 24 h, n = 81 animals) or 10(6) CA (subacute studies < or = 72 h, n = 25) . Compared with neutrophil-sufficient rats, absolute neutropenia accelerated hemodynamic collapse and respiratory distress after 10(9) CA, and pulmonary microvascular permeability was amplified . These changes evolved without increased candidemia or elevations in bioactive or antigenic serum TNF, which remained low even at death (42.3 +/- 14.8 U/ml vs . 12.6 +/- 2.9 U/ml for CY + saline, means +/- SE, P = NS) . In contrast, significant TNF in lung tissue and bronchoalveolar lavage fluid (BALF) was evident within 6 h in CY + 10(9) CA rats . Electron microscopy confirmed hyphal proliferation into alveoli from yeast within mononuclear cells in lung capillaries . Subacute disseminated candidiasis after 10(6) CA was not associated with elevated serum, lung, or BALF TNF . We conclude that differential systemic and intrapulmonary TNF production occur in CA septic shock during preexisting neutropenia, with compartmentalized TNF production in the lower respiratory tract accompanying yeast-mycelial transformation . Thus TNF is not an obligate mediator of acute candidemic shock or subacute disseminated candidiasis during CY-induced immunosuppression but may initiate pulmonary injury accompanying high-grade candidemia. Scand J Immunol, 1992 Nov, 36(5), 713 - 9 The role of BCG/PPD-activated macrophages in resistance against systemic candidiasis in mice; van 't Wout JW et al.; The main conclusions of this study are that BCG/PPD-activated macrophages, in contrast to macrophages from control mice, exhibit an increased PMA-induced production of H2O2, kill about one-third of the phagocytosed Candida albicans, and cause more than 50% inhibition of the intracellular formation of germ tubes by C . albicans . Peritoneal macrophages from mice that were colonized post-natally with C . albicans do not show increased production of H2O2 upon stimulation with PMA and the intracellular outgrowth of germ tubes is inhibited to only a limited degree . These macrophages are capable of killing about 20% of the ingested C . albicans . In vivo, the number of Candida in the kidney, spleen and liver after intravenous injection of Candida albicans is significantly lower in BCG-treated mice than in control mice . Post-natal colonization with C . albicans has only a limited effect on the outgrowth of intravenously injected C . albicans in the spleen and liver but does not influence growth in the kidney . These results indicate that acquired immunity against a systemic Candida infection involves both oxidative and non-oxidative mechanisms of intracellular killing and that these mechanisms may have different effects on the yeast and hyphal forms of C . albicans. J Med Microbiol, 1992 Nov, 37(5), 346 - 51 Yeast-specific DNA probes and their application for the detection of Candida albicans; Holmes AR et al.; Two DNA fragments cloned from the genome of Candida albicans ATCC 10261 may be useful in the rapid diagnosis of disseminated candidosis . One sequence (probe EOB1) was specific for C . albicans (positive hybridisation with 45 strains tested) . The second sequence (probe EOB2) detected C . albicans, as well as five other pathogenic Candida spp . and Saccharomyces cerevisiae, but did not react with human or bacterial DNA . Both probes were repetitive sequences in the genome of C . albicans . Probe EOB1 was used to detect, without DNA amplification, 500 C . albicans yeast cells in 1 ml of human blood. J Prosthet Dent, 1992 Nov, 68(5), 804 - 8 In vitro evaluation of Candida albicans adherence to soft denture-lining materials; Nikawa H et al.; The adherence of Candida albicans to seven commercial soft denture-lining materials was studied in vitro with BCA protein assay reagent . A good correlation was observed between the amount of protein in yeast cells and the number of yeasts (r = 0.993, p < 0.01), and it was revealed that the adherence of C . albicans to bare surfaces of these soft denture-lining materials correlated well with their relative hydrophobic properties (r = 0.905, p < 0.01); thus there was consistency with the thermodynamic theory . These results combined corroborated the accuracy of this method . To know the effect of pellicle on fungal adherence, the adherence of C . albicans to saliva-coated samples was examined . It was revealed that neither the amount of protein adsorbed by substrates nor the adherence of yeast to saliva-coated substrates correlated with the relative hydrophobic properties of these samples, suggesting that factors other than hydrophobic interaction play an important role in the adherence of C . albicans to pellicle-coated soft liners and tissue conditioners. Int J Dermatol, 1992 Nov, 31(11), 783 - 5 Candida albicans--saprophyte or pathogen? Jaafar R, Pettit JH. Skin scrapings taken from toe spaces of 200 healthy volunteers and from toe webs and groins of 150 pediatric patients were cultured for Candida albicans using the serum germ-tube test . The results showed that Candida albicans can be isolated in about 15% of normal toe spaces and 14% of children with normal groins . Although Candida albicans can be found in various grades of athlete's foot and also in some abnormal groins, we believe that it is not necessarily responsible for these conditions and is often present at these sites only as a saprophyte. Radiology, 1992 Nov, 185(2), 327 - 35 Gastrointestinal tract in the immunocompromised host: opportunistic infections and other complications; Wall SD et al.; In the decade since the early 1980s, the increasing use of immunosuppressive therapy for cancer and autoimmune disease, as well as for organ transplantation, has combined with the acquired immunodeficiency syndrome epidemic to increase greatly the incidence of opportunistic infections and other complications of the gastrointestinal tract . Consequently, barium fluoroscopic and cross-sectional imaging studies tailored to address these problems are no longer uncommon . Although overlap exists, there are radiographic patterns that can direct the diagnosis to an opportunistic infection and sometimes to a specific pathogen . This article describes and illustrates the radiographic findings of gastrointestinal superinfection with Candida albicans, cytomegalovirus, Cryptosporidium spp, herpes simplex virus, Mycobacterium tuberculosis, M avium-intracellulare, and human immunodeficiency virus . Other gastrointestinal tract complications of immunosuppression are discussed, including graft-versus-host disease following bone marrow transplantation, typhlitis, and pseudomembranous colitis. J Infect Dis, 1992 Nov, 166(5), 1103 - 12 Identification of a mannoprotein fraction from Candida albicans that enhances human polymorphonuclear leukocyte (PMNL) functions and stimulates lactoferrin in PMNL inhibition of candidal growth; Palma C et al.; Mannoprotein fractions of Candida albicans were assayed for their effects on the anticandidal activity of human polymorphonuclear leukocytes (PMNL) . One fraction, MP-F2, enhanced PMNL inhibition of candidal growth in vitro as potently as bacterial lipopolysaccharide (LPS), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin-8 . MP-F2-mediated PMNL activation was manifested on yeast and mycelial forms of the fungus, required the integrity of the mannan, and was due to an increase in the actual number of phagocytic PMNL rather than to a greater ingestion of fungal cells by each individual neutrophil . While not inducing augmented O2 production or degranulation of azurophilic granules, MP-F2 strongly stimulated the release of lactoferrin . Lactoferrin inhibited candidal growth in the absence of PMNL, and anti-lactoferrin antibodies reversed both this inhibition and the PMNL activation by MP-F2, GM-CSF, and LPS . Thus, PMNL may be activated by relevant candidal mannoproteins, and release of lactoferrin may add to other antimicrobial mechanisms of PMNL for the control of candidal infections. J Bacteriol, 1992 Nov, 174(21), 6992 - 6 Cloning and characterization of a Candida albicans maltase gene involved in sucrose utilization; Geber A et al.; In order to isolate the structural gene involved in sucrose utilization, we screened a sucrose-induced Candida albicans cDNA library for clones expressing alpha-glucosidase activity . The C . albicans maltase structural gene (CAMAL2) was isolated . No other clones expressing alpha-glucosidase activity . were detected . A genomic CAMAL2 clone was obtained by screening a size-selected genomic library with the cDNA clone . DNA sequence analysis reveals that CAMAL2 encodes a 570-amino-acid protein which shares 50% identity with the maltase structural gene (MAL62) of Saccharomyces carlsbergensis . The substrate specificity of the recombinant protein purified from Escherichia coli identifies the enzyme as a maltase . Northern (RNA) analysis reveals that transcription of CAMAL2 is induced by maltose and sucrose and repressed by glucose . These results suggest that assimilation of sucrose in C . albicans relies on an inducible maltase enzyme . The family of genes controlling sucrose utilization in C . albicans shares similarities with the MAL gene family of Saccharomyces cerevisiae and provides a model system for studying gene regulation in this pathogenic yeast. J Bacteriol, 1992 Nov, 174(21), 6789 - 99 Molecular cloning of cDNA and analysis of protein secondary structure of Candida albicans enolase, an abundant, immunodominant glycolytic enzyme; Sundstrom P et al.; We isolated and sequenced a clone for Candida albicans enolase from a C . albicans cDNA library by using molecular genetic techniques . The 1.4-kbp cDNA encoded one long open reading frame of 440 amino acids which was 87 and 75% similar to predicted enolases of Saccharomyces cerevisiae and enolases from other organisms, respectively . The cDNA included the entire coding region and predicted a protein of molecular weight 47,178 . The codon usage was highly biased and similar to that found for the highly expressed EF-1 alpha proteins of C . albicans . Northern (RNA) blot analysis showed that the enolase cDNA hybridized to an abundant C . albicans mRNA of 1.5 kb present in both yeast and hyphal growth forms . The polypeptide product of the cloned cDNA, which was purified as a recombinant protein fused to glutathione S-transferase, had enolase enzymatic activity and inhibited radioimmunoprecipitation of a single C . albicans protein of molecular weight 47,000 . Analysis of the predicted C . albicans enolase showed strong conservation in regions of alpha helices, beta sheets, and beta turns, as determined by comparison with the crystal structure of apo-enolase A of S . cerevisiae . The lack of cysteine residues and a two-amino-acid insertion in the main domain differentiated C . albicans enolase from S . cerevisiae enolase . Immunofluorescence of whole C . albicans cells by using a mouse antiserum generated against the purified fusion protein showed that enolase is not located on the surface of C . albicans . Recombinant C . albicans enolase will be useful in understanding the pathogenesis and host immune response in disseminated candidiasis, since enolase is an immunodominant antigen which circulates during disseminated infections. Infect Immun, 1992 Nov, 60(11), 4734 - 9 Characterization of a fucoside-binding adhesin of Candida albicans; Tosh FD et al.; Candida albicans GDH 2346 produces extracellular polymeric material (EP) which contains a mannoprotein adhesin with a lectin-like affinity for fucose-containing glycosides . EP isolated from culture supernatants of this strain was used as starting material for purification of the adhesin . The purification protocol involved a stepwise treatment of EP with N-glycanase, papain, and dilute alkali to cleave the protein and carbohydrate portions of the mannoprotein molecule . Fucoside-binding protein fragments were then recovered by affinity adsorption with the trisaccharide determinant of the H (type 2) blood group antigen which terminates in a residue of L-fucose . The purified adhesin was devoid of carbohydrate and inhibited yeast adhesion to buccal epithelial cells 221 times more efficiently, on a protein weight basis, than did EP . Adhesion inhibition reached a maximum of 78 to 80% at an adhesin concentration of 10 micrograms ml-1 . Our results indicate that this protein is the major adhesin of yeast-phase cells of C . albicans GDH 2346 but that one or more secondary adhesion mechanisms may operate. Infect Immun, 1992 Nov, 60(11), 4898 - 906 Characterization of cell wall proteins from yeast and mycelial cells of Candida albicans by labelling with biotin: comparison with other techniques; Casanova M et al.; Candida albicans ATCC 26555 blastoconidia and blastoconidia bearing germ tubes were metabolically labelled by incubating the cells with 14C-labelled protein hydrolysate and were subsequently tagged with biotin . Double-labelled (radioactive and biotinylated) cell wall proteins and glycoproteins were extracted from intact cells of both growth forms by treatment with 2-mercaptoethanol (beta ME) and with beta-glucanases (Zymolyase) after treatment with beta ME . The beta ME- and Zymolyase-extracts were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blotted (immunoblotted) to nitrocellulose paper . Polyacrylamide gels were stained with Coomassie blue and processed for fluorography . Western blot analysis was performed either with peroxidase conjugated-concanavalin A (ConA) or Extravidin . Blotted proteins were also reacted with polyclonal antibodies and monoclonal antibodies against mannoprotein components from mycelial cell walls of the ATCC 26555 strain . Labelling with biotin allowed identification of a complex array of cell wall protein and glycoprotein components within a very wide molecular mass range (from 650 to 13 kDa) . These appeared to be genuine cell wall components . Biotinylated high-molecular-mass glycoproteins that were not stained with Coomassie blue or that appeared as poorly resolved polydisperse bands by indirect ConA-peroxidase staining of Western blots were detected as sharply defined bands following reaction with the Extravidin-peroxidase conjugate . Biotinylated molecules retained unaltered reactivities against ConA, polyclonal antibodies, and monoclonal antibodies. Infect Immun, 1992 Nov, 60(11), 4549 - 57 Poly(I.C)-induced interferons enhance susceptibility of SCID mice to systemic candidiasis; Jensen J et al.; In the absence of any demonstrable T- or B-cell responses, gnotobiotic CB-17 SCID (severe combined immunodeficient) mice not only show innate resistance to acute systemic (intravenous challenge) candidiasis but also manifest innate resistance to systemic candidiasis of endogenous (gastrointestinal tract) origin . Poly(I . C), a potent inducer of interferons (IFNs) in vivo, enhanced the susceptibility of CB-17 SCID mice to acute systemic candidiasis and to systemic candidiasis of endogenous origin, as demonstrated by increased numbers of viable Candida albicans in internal organs after poly(I . C) treatment . The poly(I . C)-enhanced susceptibility of mice to candidiasis was abrogated by in vivo treatment with antibodies to IFN-alpha, -beta, and -gamma . In vivo depletion of natural killer cells from SCID mice did not significantly enhance their susceptibility to systemic candidiasis or abrogate poly(I . C)-enhanced susceptibility . In vivo and in vitro, treatment with poly(I . C) impaired the candidacidal and phagocytic activity of thioglycollate-elicited macrophages from SCID mice . Antibody to IFN-alpha/beta or IFN-beta alone interfered with the ability of poly(I . C) to impair the candidacidal activity of macrophages from SCID mice in vitro . These data suggest that poly(I . C)-induced interferons can impair the candidacidal activity of macrophages in SCID mice and decrease their innate resistance to acute systemic candidiasis and to systemic candidiasis of endogenous origin. J Immunother, 1992 Nov, 12(4), 256 - 64 The preferential expansion of functional CD4+ lymphocyte populations in vitro; Townsend RM et al.; We describe a simple and inexpensive chemical procedure for the selective expansion of human CD4+ lymphocytes . The method employs L-leucine methyl ester (LME) to deplete monocytes and large granular lymphocytes, as well as to inhibit growth of CD8+ lymphocytes . LME treatment eliminates granular cells, but most CD8+ lymphocytes, B-lymphocytes, and CD4+ lymphocytes remain . Peripheral blood mononuclear cells (PBMCs) from normal and HIV-positive individuals are treated with LME for 1 h at ambient temperature and cultured in the presence of IL-2 to expand the cell number . Stimulation with the T-cell mitogens concanavalin A, phytohemagglutinin, or OKT3 antibody augments lymphocyte expansion and within 1-3 weeks the culture is greatly enriched (90-100%) in CD4+ lymphocytes . LME-treated lymphocytes expand up to 10-fold during culture in the presence of IL-2 alone and up to 400-fold following treatment with T-cell mitogens . The immune function of LME-treated and expanded peripheral blood lymphocytes was examined using the response to the recall antigens tetanus toxoid and Candida albicans . Fresh PBMCs exposed to these recall antigens proliferated readily . Similarly, LME-treated lymphocytes following expansion responded to these recall antigens with good fidelity to the original PBMC response patterns in four of six donors . The expanded and LME-treated lymphocytes also exhibited good mitogen responses in three of three donors . The LME procedure allows for the simple and inexpensive generation of expanded, immunologically functional, CD4+ lymphocytes. Infect Immun, 1992 Nov, 60(11), 4950 - 2 Gamma interferon modifies CD4+ subset expression in murine candidiasis; Romani L et al.; A single injection of monoclonal antibody to gamma interferon administered in conjunction with a live Candida albicans yeast cell vaccine resulted in the detection of nonprotective Th2 rather than protective Th1 responses and altered the early expression of interleukin 4 and gamma interferon mRNA in CD4+ cells. Dev Comp Immunol, 1992 Nov-Dec, 16(6), 431 - 9 In vitro study of the phagocytic processes in splenic granulocytes of the tench (Tinca tinca, L.); Pedrera IM et al.; The different stages of the phagocytic process by splenic granulocytes of Tinca tinca were studied . Adherence capacity to both endothelium and tissue substrate, mobility rate, the phagocytosis capacity for both cells (Candida albicans) and inert particles (latex beads), candidicide power, and capacity of digestion measured by nitroblue tetrazolium (NBT) reduction were evaluated in splenic granulocytes of healthy adult tench . The capacity of adherence to nylon fiber was possessed by 51% of the granulocytes . The percentage capable of adherence to smooth plastic surfaces rose with incubation time . Casein, an effective chemoattractant, increased the random mobility of the granulocytes . Phagocytosis was greater for opsonized C . albicans than for nonopsonized . However, the number of phagocytosed yeast cells destroyed by the granulocytes did not depend on whether or not the C . albicans had been previously opsonized . The phagocytosis indices and the percent phagocytosis of latex beads were greater than those obtained for the phagocytosis of C . albicans in the absence of serum . Finally, the metabolic activity in these cells following the digestion of ingested material showed a 148 +/- 31% stimulation . The results show that splenic cells of tench have the capacity to make a phagocytic response against both cells (C . albicans) and inert particles (latex beads). Rinsho Byori, 1992 Nov, 40(11), 1217 - 23 {False positive reaction in measurement of allergen-specific IgE--comparison of 3M IgE FAST-Plus Test using polystyrene well as adsorbent with Phadezym RAST}; Hagihara S et al.; Irrelevant IgE binding to cellulose discs is known to give false positive results in Phadezym RAST (Pharmacia) for the estimation of allergen-specific IgE in serum . We investigated FAST-Plus Test (3M Diagnostic Systems), an enzyme-linked sandwich type Fluoro-Allergo-Sorbent Test in which a particular allergen was coated to polystyrene well . Phadezym RAST and CAP RAST (Pharmacia) using cellulose-derivative discs as adsorbent were used as reference methods . Patients' sera which gave negative blank reactions to uncoated filter paper disc in the Phadezym RAST system were assayed for specific IgE to 6 allergens using FAST-Plus Test, CAP RAST and Phadezym RAST, and the results of the former two were compared with those of Phadezym RAST using a comparable class system . FAST-Plus Test showed variable correlations with Phadezym RAST, the correlation coefficients ranged from 0.41 to 0.97 (r = 0.462 in house dust 1, r = 0.713 in house dust 2, r = 0.412 in Candida albicans, r = 0.952 in Dermatophagoides peteronyssinus, r = 0.969 in Dermatophagoides farinae and r = 0.682 in Japanese cedar), although most of the results were within one class difference . Similar correlations were obtained between CAP RAST and Phadezym RAST . Of 3004 patients' sera tested in the past two years using Phadezym RAST, 132 (96 cases) displayed positive blank reactions to the uncoated filter paper disc . Of the 96 cases, 80 sera were assayed for binding of IgE to the uncoated cellulose-derivative disc in the CAP RAST system . 18 showed positive results up to 7 IU/ml.(ABSTRACT TRUNCATED AT 250 WORDS) Tohoku J Exp Med, 1992 Nov, 168(3), 483 - 90 Polysaccharide-coated liposomal amphotericin B for the treatment of murine pulmonary candidiasis; Miyazaki T et al.; Amylopectin-coated liposomal amphotericin B was investigated in a murine model of pulmonary candidiasis . The LD50 of amylopectin-coated liposomal amphotericin B in normal mice was more than 10.0 mg/kg, and that of conventional amphotericin B was 1.2 mg/kg . Amylopectin-coated liposomes showed twice the concentration in the lungs of conventional liposomes . Candida albicans was inoculated intratracheally into BALB/C mice . Twenty-four hours later, the number of Candida in the lungs of mice treated with amylopectin-coated liposomes was less than in those treated with conventional liposomes, and amylopectin-coated liposomes improved the survival rate of inoculated mice . Coating liposomes with amylopectin aids the targeting of amphotericin B to the lungs. Mycoses, 1992 Nov-Dec, 35(11-12), 321 - 7 Synergistic interaction of miconazole and fluconazole at sub-MIC level on Candida albicans; Mikami Y et al.; The in vitro combination effect of two azole antimycotics, miconazole and fluconazole, against Candida albicans was studied . When minimum (MIC) and sub-minimum (sub-MIC) inhibitory concentration and fractional inhibitory concentration (FIC) determinations were made, a synergistic interaction of the two agents at the concentration well below their individual MICs (at sub-MIC levels) was evidenced . The FIC index values ranged from 0.3 to 1.0 and the synergy was characterized by the potentiation of fluconazole activity with miconazole . The synergistic effect was also confirmed by a turbidometric method . On the other hand, such a synergistic effect against Candida krusei was not confirmed. Mycoses, 1992 Nov-Dec, 35(11-12), 315 - 6 Successful treatment of a Candida albicans sepsis with a combination of flucytosine and fluconazole; Scheven M et al.; A case of a severe Candida sepsis is reported, which was treated successfully by a combination therapy of flucytosine with fluconazole . After an extensive abdominal operation, a 70-year-old man developed a syndrome of fulminant sepsis due to Candida albicans with the beginnings of renal failure . The latter fact forced us to search for a therapeutic alternative to the classical amphotericin B plus flucytosine combination therapy. Biull Eksp Biol Med, 1992 Nov, 114(11), 515 - 8 {The chemiluminescence reactions of the blood neutrophils and of peritoneal exudate cells in Syrian hamsters to the intraperitoneal administration of cellular and microbial materials}; Prilutskaia MO et al.; The luminol-dependent chemiluminescence (CL) activity of peritoneal exudate cells and blood neutrophils of Syrian hamsters inoculated intraperitoneally with heat-inactivated microbial particles of Candida albicans, (C . albicans), heated irradiated normal cells and native or heated irradiated malignant tumor cells was studied . The inoculation with particles of C . albicans and heated normal cells induced significant activation of CL of peritoneal exudate cells, but did not influence the CL reaction of blood neutrophils . The inoculation of animals with nonheated irradiated tumor cells led to increase of CL response of both peritoneal exudate cells and blood neutrophils . The inoculation with heated irradiated tumor cells did not activate CL of peritoneal exudate cells and led to slight, but long-lasting decrease of CL response of blood neutrophils. Clin Exp Allergy, 1992 Nov, 22(11), 991 - 5 Stability of Candida albicans allergens during storage; Savolainen J et al.; Stability of Candida albicans allergens was studied under various storage conditions . Lyophilized extract was reconstituted with human serum albumin (NSA) diluent, glycerol-free and in the presence of 10% or 50% glycerol and stored at various temperatures for different time periods . All extracts were tested at the same time with immunoblotting using C . albicans allergic patient sera and galactosidase-labelled anti-IgE . The highest number of detected allergens in the immunoblotting pattern was found in the presence of 50% glycerol at +6 degrees C . The most important allergen of C . albicans, the 46 kD protein allergen was stable up to 10 weeks at +6 degrees C in the presence of 50% glycerol but thereafter began to lose its IgE-binding capacity . After 30 weeks more than 50% of the IgE binding had disappeared . The 27 kD protein, another important allergen, was also labile but retained the allergenicity better than the 46 kD one . The 29 kD protein allergen was stable at all storage conditions, except +37 degrees C tested even after one year . More than 6 months storage at +6 degrees C or higher temperature is, however, unacceptable even in the presence of the 50% glycerol . These findings have particular importance in the diagnosis and treatment of allergic diseases. Nucleic Acids Res, 1992 Oct 25, 20(20), 5289 - 95 Evolution of codon usage patterns: the extent and nature of divergence between Candida albicans and Saccharomyces cerevisiae; Lloyd AT et al.; Codon usage in a sample of 28 genes from the pathogenic yeast Candida albicans has been analysed using multivariate statistical analysis . A major trend among genes, correlated with gene expression level, was identified . We have focussed on the extent and nature of divergence between C.albicans and the closely related yeast Saccharomyces cerevisiae . It was recently suggested that significant differences exist between the subsets of preferred codons in these two species {Brown et al . (1991) Nucleic Acids Res . 19, 4293} . Overall, the genes of C.albicans are more A + T-rich, reflecting the lower genomic G + C content of that species, and presumably resulting from a different pattern of mutational bias . However, in both species highly expressed genes preferentially use the same subset of 'optimal' codons . A suggestion that the low frequency of NCG codons in both yeast species results from selection against the presence of codons that are potentially highly mutable is discounted . Codon usage in C.albicans, as in other unicellular species, can be interpreted as the result of a balance between the processes of mutational bias and translational selection . Codon usage in two related Candida species, C.maltosa and C.tropicalis, is briefly discussed. FEMS Microbiol Lett, 1992 Oct 15, 76(3), 255 - 9 Chitin synthetase activity is bound to the plasma membrane and to a cytoplasmic particulate fraction in Candida albicans germ tube cells; Gozalbo D et al.; Subcellular distribution of chitin synthetase has been studied in germ tubes of Candida albicans . Two fractions with synthetase activity were separated from cell homogenates: (i) a mixed membrane fraction where the enzyme, partly in an active form, is associated with the plasma membrane (isopycnic centrifugation of mixed membrane fraction on linear sucrose gradients resolved a unique peak of activity matching with {3H}ConA-labelled membranes at a buoyant density of 1.195 g/ml); and (ii) a cytoplasmic fraction containing fully zymogenic enzyme associated with particles whose buoyant density (determined by isopycnic centrifugation on linear sucrose gradients) depended on the cell breakage conditions . The actual cytoplasmic fraction-enzyme may correspond to particles with buoyant density 1.135 g/ml (chitosomes), whereas the enzyme particles with other densities (1.085 and 1.165 g/ml) probably originated during cell disruption, as has been reported previously to occur during the preparation of yeast cell homogenates. Proc Natl Acad Sci U S A, 1992 Oct 15, 89(20), 9410 - 4 Dominant negative selection of heterologous genes: isolation of Candida albicans genes that interfere with Saccharomyces cerevisiae mating factor-induced cell cycle arrest; Whiteway M et al.; We have used a genomic library of Candida albicans to transform Saccharomyces cerevisiae and screened for genes that act similarly to dominant negative mutations by interfering with pheromone-mediated cell cycle arrest . Six different plasmids were identified from 2000 transformants; four have been sequenced . One gene (CZF1) encodes a protein with structural motifs characteristic of a transcription factor . A second gene (CCN1) encodes a cyclin homologue, a third (CRL1) encodes a protein with sequence similarity to GTP-binding proteins of the RHO family, and a fourth (CEK1) encodes a putative kinase of the ERK family . Since CEK1 confers a phenotype similar to that of the structurally related S . cerevisiae gene KSS1 but cannot complement a KSS1 defect, it is evident that dominant negative selection can identify proteins that complementation screens would miss . Because dominant negative mutations exert their influence even in wild-type strain backgrounds, this approach should be a general method for the analysis of complex cellular processes in organisms not amenable to direct genetic analysis. FEBS Lett, 1992 Oct 12, 311(1), 51 - 4 Enzymatic and immunological detection of G protein alpha-subunits in the pathogenic fungus Candida albicans; Paveto C et al.; GTP stimulation of adenylyl cyclase from the dimorphic pathogenic fungus Candida albicans is greatly enhanced by preincubation of membrane proteins with cholera toxin, NAD and ATP . In the presence of {32P}NAD the toxin catalyzes the covalent incorporation of radioactivity into a membrane protein of 40 kDa . Pertussis toxin catalyzes the transference of the radioactivity from {32P}NAD to a 32 kDa protein . Two major proteins of 40-42 and 30-32 kDa can also be recognized in Western blots by an anti G alpha-common antibody . The results support the idea that G proteins are part of the hormone sensory transduction chain of Candida {(1990) Biochem . Biophys . Res . Commun . 167, 1177-1183}. Antimicrob Agents Chemother, 1992 Oct, 36(10), 2239 - 44 Modulation of interactions of Candida albicans and endothelial cells by fluconazole and amphotericin B; Ghannoum MA et al.; Using an in vitro model of intravascular infection, we examined the effects of exposure to subinhibitory concentrations of fluconazole and amphotericin B on the ability of Candida albicans to adhere to and damage human umbilical vein endothelial cells . Incubation of the organisms for 18 h in 0.5x the MICs of fluconazole and amphotericin B inhibited endothelial cell adherence by 22 and 91%, respectively (P less than 0.001 for each drug) . Candida-induced endothelial cell injury was also decreased by exposing the organisms to the antifungal drugs while in contact with the endothelial cells . Fluconazole inhibited damage by approximately 50% at concentrations ranging from 0.25x to 5x the MIC (P less than 0.01 for each concentration) . Exposure to amphotericin B at 0.5x the MIC completely blocked the ability of the organisms to injure endothelial cells . The capacities of the antifungal agents to inhibit endothelial cell injury paralleled their abilities to suppress candidal germination . Organisms exposed to up to 5x the MIC of fluconazole had diminished, but still detectable, germ tube production and elongation, whereas incubation in 0.5x the MIC of amphotericin B completely abrogated germination . In addition to their direct effects on the growth of C . albicans, fluconazole and amphotericin B may decrease the ability of the fungus to disseminate hematogenously by inhibiting the organisms' capacity to adhere to and injure endothelial cells. Oral Microbiol Immunol, 1992 Oct, 7(5), 315 - 20 Inhibition of Candida albicans by the Peroxidase/SCN-/H2O2 system; Lenander-Lumikari M; Effects of the salivary peroxidase (SPO) system on the growth, glucose uptake and metabolic activities of oral bacteria are well documented but the effects on oral fungi are virtually unknown . Therefore, the viability of Candida albicans (ATCC 28366) exposed to the peroxidase/SCN-/H2O2 system was studied in sterilized saliva, in phosphate-buffered saline (PBS) and in potassium chloride . The growth of C . albicans in glucose-supplemented saliva was faster at pH 5.5 than at pH 7 . The addition of the complete SPO (or lactoperoxidase) system to either sterilized saliva, KCl (50 microM) or PBS at pH 5.5 inhibited dose-dependently the viability of C . albicans in KCl, but no inhibition was found in PBS or saliva . Maximal inhibition was achieved in 2 h and with > 320 microM of peroxidase-generated HOSCN/OSCN- . However, physiological salivary concentrations of phosphate (> or = 1.0 mM) and PBS blocked the antifungal effect of HOSCN/OSCN- . The relative proportions of SCN- and H2O2 were critical to the antifungal effects . With 0.2 mM KSCN, a complete loss of viability was achieved, though the HOSCN/OSCN- concentrations did not exceed 100 microM . It is concluded that C . albicans is sensitive to HOSCN/OSCN- but salivary concentrations of phosphate block the antifungal effect of the peroxidase systems. Mycopathologia, 1992 Oct, 120(1), 11 - 3 Influence of alkaline pH on the direct lethal action of miconazole against Candida albicans; Beggs WH; The imidazole group of miconazole is subject to protonation (pKa approximately 6.5) . Earlier we suggested that the direct lethal action (DLA) of miconazole against Candida albicans requires nonprotonated drug molecules . DLA declined in intensity as pH was decreased from 6.0 . At pH > 6.5 most molecules of miconazole exist in the nonprotonated state, but drug also becomes less soluble . Viability studies were designed to assess DLA in relation to alkaline pH . DLA was clearly inhibited with increasing as well as decreasing pH (i.e., pH < 6.0 and > 7.0), suggesting that nonprotonated neutral drug molecules must be in solution or in extremely small aggregates to elicit DLA, and that the nonprotonated species itself is more soluble at pH 6.0-7.0 than under more alkaline conditions. Arzneimittelforschung, 1992 Oct, 42(10), 1246 - 50 Preliminary evaluation of immunoadjuvant activity of an orally administered glucan extracted from Candida albicans; Nicoletti A et al.; The immunoadjuvant activity of an orally administered glucan (Glucanil, Gluimmun) was investigated in mice . Glucan was extracted from Candida albicans ATCC 20955 and purified by an alkali-acid and detergent treatment . In this study the chronic intravenous infection with Candida albicans (treated or not with amphotericin B) or Staphylococcus aureus was the experimental model . Moreover the production of interleukin-2 was evaluated in treated animals . Oral treatment with glucan at 1 mg/mouse/day repeated doses, starting from 10 days before the experimental infection, significantly increased polymorphonuclear leukocytes and peripheral monocytes number . A significant increase in number and in vitro candidacidal activity was also observed for alveolar macrophages . The resistance towards systemic infection with Candida albicans or Staphylococcus aureus increased, significantly reducing the growth of microorganisms in the kidneys of infected animals . Glucan significantly increased the candidacidal spleen cells activity and synergized with amphotericin B chemotherapeutic action . Higher doses (eg . 2 or 5 mg/mouse) were not effective . A 10 days oral treatment with 1 mg/mouse/d significantly increased the interleukin-2 production . Toxicological studies showed that glucan is highly tolerated. J Acquir Immune Defic Syndr, 1992 Oct, 5(10), 1039 - 46 The identification and tracking of Candida albicans isolates from oral lesions in HIV-seropositive individuals; Miyasaki SH et al.; Restriction fragment polymorphism analysis was used to investigate the identity and genotypic relatedness of Candida albicans strains isolated from human immunodeficiency virus (HIV)-infected patients with or without oral candidiasis and from some of their sexual partners . Use of the species-specific DNA probe Ca3 revealed that most subjects carried a single distinct C . albicans strain throughout the course of the study, during both symptomatic and asymptomatic periods . Sexual partners were more likely to carry the same or similar C . albicans isolates than unrelated subjects, raising the possibility of transmission via intimate contact . One patient appeared to acquire his partner's isolate, which then became predominant in both partners in subsequent isolations . These findings indicate that recurrent oral candidiasis is usually caused by a single persistent strain unique to each patient, but that in some cases transmission via intimate contact may occur between sexual partners. Clin Infect Dis, 1992 Oct, 15(4), 701 - 3 Biliary concentrations of fluconazole in a patient with candidal cholecystitis: case report; Bozzette SA et al.; A patient with acute cholecystitis due to Candida albicans and Candida parapsilosis was treated with a percutaneous cholecystostomy and daily intravenous fluconazole . Fluconazole levels in serum and bile were measured by gas chromatography . Fluconazole levels in the bile were equal to those in the blood for the first 8 hours after a dose and were slightly higher than serum levels after that . Bile levels after an oral dose of fluconazole were 15% higher than levels achieved after intravenous administration of the drug . The infection was cured after 2 weeks of treatment . This experience suggests that sufficient fluconazole is excreted in the bile to be effective for treatment of biliary infections due to susceptible yeasts. Am J Obstet Gynecol, 1992 Oct, 167(4 Pt 1), 1086 - 91 Infection and labor . VIII . Microbial invasion of the amniotic cavity in patients with suspected cervical incompetence: prevalence and clinical significance; Romero R et al.; OBJECTIVE: The purpose of this study was to determine the prevalence and clinical significance of microbial invasion of the amniotic cavity in patients presenting with cervical dilatation in the midtrimester of pregnancy . STUDY DESIGN: Amniocentesis for microbial studies was performed in women admitted with cervical dilatation > or = 2 cm, intact membranes, and without active labor between 14 and 24 weeks of gestation . Amniotic fluid was cultured for aerobic and anaerobic bacteria, as well as for mycoplasmas . Gram stain was performed on all samples . RESULTS: The prevalence of microbial invasion of the amniotic cavity was 51.5% (17/33) . The most common microbial isolates were Ureaplasma urealyticum, Gardnerella vaginalis, Candida albicans, and Fusobacterium sp . All patients with microbial invasion of the amniotic cavity had complications . Patients who underwent cervical cerclage in the presence of a positive amniotic fluid culture had rupture of membranes, clinical chorioamnionitis, or pregnancy loss . On the other hand, the prognosis of patients with a negative amniotic fluid culture was better than that of patients with a positive culture . Of 16 patients with a negative amniotic culture, nine were delivered at > 34 weeks . CONCLUSIONS: (1) Microbial invasion of the amniotic cavity occurs frequently in women presenting with cervical dilatation in the midtrimester; (2) the microbiologic state of the amniotic cavity is an important prognostic factor for pregnancy outcome; (3) amniocentesis to determine the microbiologic characteristics of the amniotic cavity should be considered before a cerclage is placed in women presenting with cervical dilatation in the midtrimester. Oral Surg Oral Med Oral Pathol, 1992 Oct, 74(4), 492 - 8 Effects of chronic Candida albicans in the hamster cheek pouch; McMillan MD et al.; Sixty-four adult male hamsters had a suspension of either C . albicans (UO1) or C . albicans (ATCC 10261) placed in their cheek pouches once a week for up to 9 months . Four hamsters from both experimental groups, along with two untreated control hamsters, were killed at monthly intervals after the initial inoculation . Sections taken from the hamsters and examined in the light microscope showed that all experimental pouches had some or all of the following localized changes: inflammation and increased vascularity of the connective tissue; epithelial inflammation and microabscesses; hyperkeratosis; and isolated rete ridges similar to those in control pouches . C . albicans, usually the yeast form, was present on the exposed surface and between hyperplastic keratin squames . There was no hyphal invasion of the epithelium . Rather than being a true long-term study of chronic infection by C . albicans, the changes seen were probably the result of repetitive, more short-term responses after multiple inoculations. Oral Surg Oral Med Oral Pathol, 1992 Oct, 74(4), 451 - 4 Immunodiagnosis in oral candidiasis . A review; Jeganathan S et al.; Detection of anti-Candida antibodies in sera and saliva of patients with oral candidiasis has been regarded as a valuable laboratory technique in the diagnosis of the lesion . However, despite considerable research, the value of candidal immunodiagnosis remains controversial . Conflicting conclusions about the sensitivities and specificities of these techniques as applied to human sera and saliva have appeared . These controversies have arisen because of the use of different antigen preparations and immunologic techniques . For the present, the use of purified cytoplasmic protein antigen of Candida albicans and the ELISA technique seems to be the most reliable laboratory method. J Toxicol Environ Health, 1992 Oct, 37(2), 265 - 75 Procedure for evaluating changes in respiratory symptoms of experimentally asthma-induced guinea pigs by a personal computer; Kitabatake M et al.; An automated system was developed for evaluating changes in respiratory symptoms in guinea pigs over a long period with a personal computer . The data on breathing curves obtained with a body plethysmograph were analyzed to determine respiratory rate, expiration/inspiration ratio, ventilation ratio, and other parameters . With this system, respiratory changes in guinea pigs, such as increase or decrease of respiratory rate, expiration/inspiration ratio, and ventilation ratio, and death of animals could be easily observed . Investigation of delayed respiratory response to Candida albicans in sensitized guinea pigs and of the effects of SO2 or NO2 exposures on its response was carried out using this system . Respiratory changes in delayed respiratory response were mostly increased respiration rate and succeeding expiratory prolongation being noted just before death . In the influences of SO2 or NO2 exposure on delayed respiratory response, increase of respiratory rate in NO2 and expiratory and inspiratory prolongation in SO2 were found . This system should prove useful for evaluating changes in respiratory symptoms due to toxic agents, medicines, and air pollutants in small animals. J Med Microbiol, 1992 Oct, 37(4), 291 - 5 Initial organ localisation of blood-borne Candida albicans in a rat model of disseminated candidosis; Katz S et al.; The rat was evaluated as an experimental model for disseminated candidosis by quantitating blood clearance and initial organ localisation of 3H-leucine-labelled Candida albicans after intravenous injection into the tail or portal vein . Viable or formalin-killed blastoconidia or viable blastoconidia with germ tubes were injected into experimental animals . Blood and tissue samples were obtained up to 24 h after injection and processed for liquid scintillation counting (to determine the distribution of labelled yeasts) and quantitation of viable organisms . Yeasts were cleared rapidly after intravenous (i.v.) injection by either route, i.e., < 5% of the radioactivity was detected in the blood after 5 min . The liver and lung were the major organs that sequestered blood-borne yeasts 1 h after tail vein injection (42.5 SD 15% and 41.4 SD 6.4% of labelled yeasts injected, respectively) . However, injections via the portal vein resulted in trapping of the yeasts predominantly by the liver . Recovery of radioactivity and viable yeasts from all organs except the kidneys decreased with time . Overall, the results indicated that the rat might serve as a reliable model for short-term studies on organ distribution and thus contribute to our understanding of tissue trophism in candidosis. J Prosthet Dent, 1992 Oct, 68(4), 683 - 91 Characterization of acquired denture pellicle from healthy and stomatitis patients; Edgerton M et al.; Little information is available about the acquired pellicle layer that is formed on denture surfaces or its role in regulating microbial colonization of the prosthetic surface . Because denture-induced stomatitis is associated with increased numbers of Candida albicans and other microorganisms on the denture surface, the acquired denture pellicle (ADP) may play a role in modulating this colonization . This study examined and compared ADP from healthy patients and patients with stomatitis by chemical and immunochemical methods . The ADP was found to be composed of a selectively adsorbed layer containing salivary amylase, high molecular weight mucin (MG1), lysozyme, albumin, and sIgA . Salivary cystatins, proline-rich proteins, and low molecular weight mucin (MG2) were not detected . ADP amino acid composition was distinct from any of the ductal salivas, but had many similarities with enamel pellicle . Immunoblots of ADP from patients with stomatitis identified additional serum components, degradation products, and C . albicans cell components that were not detected in ADP from healthy patients . Quantification of these molecules in ADP could lead to a diagnostic test for oral mucosal disease underlying a denture base . Identification of specific molecules in denture pellicle that promote adhesion of C . albicans may elucidate a mechanism of fungal cell colonization on the denture surface . Future studies that chemically modify the denture acrylic resin surface to immobilize antimicrobial proteins may be a means of decreasing pathogenic plaque development. J Prosthet Dent, 1992 Oct, 68(4), 629 - 33 An in vitro evaluation of simplified quantitative diagnostic aids for detection of Candida albicans; Nikawa H et al.; Sensitivities and abilities of quantitative detection for Candida albicans of five simplified diagnostic aids for candidosis or denture stomatitis--Microstix-Candida, Stomastat medium, Mizuno- Takada medium, CA-TG medium, and "milk test"--were examined in vitro, and the characteristics or the indications for clinical use of these summarized. Infect Immun, 1992 Oct, 60(10), 4221 - 9 Identification of a 58-kilodalton cell surface fibrinogen-binding mannoprotein from Candida albicans; Casanova M et al.; Treatment of both yeast (blastoconidia) and hyphal (blastoconidia with germ tubes) cells of Candida albicans with beta-mercaptoethanol (beta ME) releases a complex array of cell wall-bound proteins and glycoproteins . Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western immunoblotting with fibrinogen-anti-fibrinogen antibody allowed the identification of a 58-kDa mannoprotein (mp58) in both extracts which specifically interacts with human fibrinogen . Treatment of intact cells with low concentrations of beta-glucanase (Zymolyase 20T) for short periods or with beta ME abolished or significantly reduced binding of fibrinogen . A rabbit polyclonal antiserum was raised against the purified mp58 species released by beta ME from germinated blastoconidia (PAb anti-mp58) . By Western blotting, the antiserum cross-reacted with the homologous 58-kDa fibrinogen-binding mannoprotein present in beta ME extracts from blastoconidia, and by indirect immunofluorescence, the antiserum labelled both yeast cells and hyphae, yet reactivity was found primarily on the cell surface of filamentous forms . Immunostaining of human infected tissue sections with PAb anti-mp58 showed that the mp58 species is also expressed in vivo; in this case, the species is in the forms of both yeast and hyphal elements similarly labelled by the antiserum . Purified immunoglobulin G fraction from the antiserum did not alter the binding of fibrinogen as determined by a modified enzyme-linked immunosorbent assay and Western blotting . The N- and O-glycosidically linked carbohydrates represent 18 to 20% and 3 to 4%, respectively, of the molecular mass of the mp58 . O-linked sugar residues may be involved in the interaction of the molecule with fibrinogen. Infect Immun, 1992 Oct, 60(10), 4168 - 78 Retrovirus-induced immunodeficiency in mice exacerbates gastrointestinal candidiasis; Cole GT et al.; Dysfunction of neutrophils in patients infected with human immunodeficiency virus is at least partly responsible for secondary microbial diseases in these individuals, including invasive gastrointestinal (GI) candidiasis . Immunoregulatory disturbances associated with the development of AIDS in human immunodeficiency virus-infected patients exacerbates Candida albicans infection of the upper GI tract and frequently leads to oropharyngeal and esophageal candidiasis . In this article, we present the first report of a murine model of invasive GI candidiasis associated with an AIDS-related murine immunodeficiency syndrome that results from infection of C57BL/6 mice with a previously described retrovirus complex (LP-BM5) . Mice of the inbred strain were infected with C . albicans by oral-intragastric inoculation as infants and with the retrovirus by the intraperitoneal route 30 days later . Control mice of the same strain were infected with C . albicans as above and subsequently infected with the avirulent, ecotropic helper virus (MBI-5) . Animals were killed 90 days after retroviral challenge . Total and differential blood cell counts, CD4+ T-cell counts in the spleen, and the histopathology of the gastric mucosa of experimental and control animals were determined . The virulent LP-BM5-infected animals developed murine AIDS and showed eruptive and suppurative lesions, with associated C . albicans mainly in regions of the cardial-atrium fold of the stomach . Well-defined abscesses with entrapped C . albicans hyphae were observed in the region of the cardial-atrium fold of control mice . A significant increase in the number of C . albicans CFU in homogenized and plated segments of the GI tract was recognized in mice with murine AIDS versus the control animals . The murine model of GI candidiasis reported here permits examination of the nature of C . albicans interaction with the gastric mucosa both in the immunocompetent host under conditions in which the yeast exists predominantly as a commensal organism and in the immunosuppressed host during progressive stages of AIDS induced by a retroviral infection. Infect Immun, 1992 Oct, 60(10), 4003 - 8 Tumor necrosis factor and interleukin-6 in Candida albicans infection in normal and granulocytopenic mice; Steinshamn S et al.; We administered a neutralizing monoclonal antibody to tumor necrosis factor (TNF) during infection with Candida albicans in normal and granulocytopenic mice . Mice were rendered granulocytopenic (less than 0.1 x 10(9) granulocytes per liter) with cyclophosphamide . Growth of C . albicans from the kidneys was significantly increased in normal mice treated with the antibody to TNF, compared with that in control mice, after 36 h (3.6 x 10(4) +/- 1.2 x 10(4) CFU per kidney versus 9.1 x 10(3) +/- 6.2 x 10(3) CFU per kidney; P less than 0.05) and after 72 h (3.7 x 10(6) +/- 2.7 x 10(6) CFU per kidney versus 2.3 x 10(4) +/- 1.3 x 10(4) CFU per kidney; P less than 0.01) . In granulocytopenic mice, the antibody to TNF had no effect on the growth of C . albicans from the kidneys . Furthermore, our study showed that the cytokines TNF and interleukin-6 (IL-6) were produced in a dose-dependent manner during C . albicans infection . TNF was detectable between 6 and 60 h, with peak levels at 24 h . Both TNF and IL-6 levels were significantly higher in cyclophosphamide-treated mice than in normal mice . Heat-inactivated C . albicans induced a TNF response different from that induced by viable C . albicans, with an early peak occurring at 3 to 4 h and declining to non-detectable levels after 15 to 24 h . Peak levels of TNF obtained with heat-inactivated C . albicans were lower than those obtained with viable C . albicans . Our study demonstrates that TNF and IL-6 are produced systemically during C . albicans infection and suggests that TNF is essential for granulocyte antifungal activity in vivo. Dent Clin North Am, 1992 Oct, 36(4), 857 - 78 Candida and candidosis . Epidemiology, diagnosis and therapeutic management; Fotos PG et al.; Infections caused by Candida species comprise one of the most common oral disease conditions encountered in the practice of dentistry . Gradual changes in population demographics have been accompanied by an increased incidence in candidal and related opportunistic infection rates . Candida albicans and other candidal species traditionally have been recognized as opportunistic pathogens . Recent advances in both the scientific basis for and the clinical significance of candidal organisms, however, have demonstrated these fungi to be distributed widely and to be important contributors to a broad range of mucosal and systemic disease conditions . These factors have allowed for a better understanding of fungal pathogenesis as it affects human oral disease through improvements in clinical and laboratory diagnosis and the therapeutic management of candidosis. Ann Hematol, 1992 Oct, 65(4), 193 - 5 Successful second allogeneic bone marrow transplantation in a relapsed acute myeloid leukemia patient with fungal liver abscess; Tanaka J et al.; Disseminated fungal infection not infrequently complicates the course of allogeneic bone marrow transplantation (allo BMT) in severely immunocompromised patients, and the prognosis of BMT patients who develop systemic fungal infection is very poor . We describe a patient who developed disseminated Candida albicans infection with liver abscess after the first allo BMT for acute myelogenous leukemia (FAB M2) . The infection was successfully eradicated by the administration of miconazole and amphotericin B . However, 1 year after the first allo BMT, the patient suffered a relapse of acute myelogenous leukemia with fungal liver abscess . A second allo BMT, accelerating granulocyte recovery by recombinant human granulocyte colony-stimulating factor (rhG-CSF), was successfully performed and the fungal liver abscess resolved with a combination therapy of fluconazole and amphotericin B . The patient is alive and free of both leukemia and fungal disease more than 37 months after the first allo BMT and 25 months after the second allo BMT. Infect Immun, 1992 Oct, 60(10), 4100 - 10 Structural identification of an epitope of antigenic factor 5 in mannans of Candida albicans NIH B-792 (serotype B) and J-1012 (serotype A) as beta-1,2-linked oligomannosyl residues; Shibata N et al.; In previous articles, we reported the presence of phosphate-bound beta-1,2-linked oligomannosyl residues in the mannans of strains of Candida albicans serotypes A and B and Candida stellatoidea . To identify the antigenic factor corresponding to this type of oligomannosyl residue, a relationship between chemical structure and antigenic specificity in the mannans of C . albicans NIH B-792 (serotype B, B-strain) and C . albicans J-1012 (serotype A, J-strain) was investigated by using a combination of two-dimensional 1H nuclear magnetic resonance spectroscopy of H-1, H-2, and H-5 regions in the mannans and an enzyme-linked immunosorbent assay that employed concanavalin A-coated microtiter plates . It was shown in the present 1H nuclear magnetic resonance study that an examination of chemical shifts not only in the H-1 region but also in the H-5 region was useful for the quantitative determination of the phosphate-bound beta-1,2-linked oligomannosyl residues . In the enzyme-linked immunosorbent assay using concanavalin A-coated plates, it was revealed that, of factor sera 1, 4, and 5, only factor serum 5 showed a reactivity proportional to the densities of the beta-1,2-linked oligomannosyl residues of the mannan subfractions of different phosphate contents that had been prepared from the bulk B-strain mannan by DEAE-Sephadex chromatography . The above results indicate that the phosphate-bound beta-1,2-linked oligomannosyl residues, Manp beta 1----(2Manp beta 1----)n2Man (n = 0-5), correspond to antigenic factor 5. J Clin Microbiol, 1992 Oct, 30(10), 2674 - 9 Comparison of molecular typing methods for Candida albicans; Magee PT et al.; Four molecular approaches to determining the types of Candida albicans strains were compared . The strains used were those whose repeated DNA (ribosomal and mitochondrial) EcoRI restriction fragment length polymorphisms (RFLP) were determined by Stevens et al . (D . A . Stevens, F . C . Odds, and S . Scherer, Rev . Infect . Dis . 12:258-266, 1990) . Scherer and Stevens (S . Scherer and D . A . Stevens, Proc . Natl . Acad . Sci . USA 85:1452-1456, 1988) used the same strains to examine the Southern blots of genomic EcoRI digests probed with the repeated sequence 27A . The results of these investigators were compared with determinations of RFLPs generated from repeated DNA by the enzyme HinfI and examination of the karyotypes of strains under two sets of conditions, one for the smaller chromosomes and one for the larger ones . Analysis of RFLPs of repeated DNA is most convenient but shows the lowest degree of resolution . Use of the repeated sequence and use of karyotype have very high resolution, but the former method is more convenient than the latter . HinfI digestion is more sensitive than EcoRI digestion but equally convenient . By using all four methods, separate types were identified for 18 of the 20 strains examined. J Chemother, 1992 Oct, 4(5), 268 - 70 Effects of miocamycin and erythromycin on polymorphonuclear cell function; Bacci P et al.; Previous studies have shown that erythromycin can enter phagocytic cells, stimulating their functional activity . In this work we compared the effects of erythromycin and another newer macrolide antibiotic, miocamycin, on a series of in vitro tests aimed at evaluating their influence on polymorphonuclear cell (PMN) functions . Results indicate that erythromycin induces an increase in leukotriene B4 production in PMNs, while chemotaxis, killing of Candida albicans and respiratory burst are not influenced, at least at the doses used in this study . On the contrary, all these activities are significantly enhanced following incubation with miocamycin, and the response varies according to the antibiotic concentration. Antimicrob Agents Chemother, 1992 Oct, 36(10), 2131 - 8 Characterization of DNA topoisomerase I from Candida albicans as a target for drug discovery; Fostel JM et al.; Candida albicans is an opportunistic pathogen responsible for life-threatening infections in persons with impaired immune systems . Topoisomerase I is a potential target for novel antifungal agents; however, in order for this enzyme to be a therapeutically useful target, it needs to be demonstrated that the fungal and human topoisomerases differ sufficiently as to allow the fungal topoisomerase to be selectively targeted . To address this question, we isolated the topoisomerase I from C . albicans and compared its biochemical properties with those of the mammalian enzyme . Similar to other eukaryotic type I topoisomerases, the C . albicans type I topoisomerase has an apparent molecular mass of 102 kDa and covalently links to the 3' end of DNA, as shown after the reaction is interrupted by sodium dodecyl sulfate . Topoisomerase poisons such as camptothecin act by stabilizing the cleavage complex formed by the topoisomerase I and DNA . We observed that the C . albicans and mammalian type I topoisomerases differ in that the C . albicans cleavage complex is approximately 10-fold less sensitive to camptothecin than the mammalian cleavage complex is . In addition, we found that the antifungal agent eupolauridine can stabilize the cleavage complex formed by both the C . albicans and human topoisomerases and that the response of the C . albicans topoisomerase I to this drug is greater than that of the human enzyme . Thus, the topoisomerase I from C . albicans is sufficiently distinct from the human enzyme as to allow differential chemical targeting and will therefore make a good target for antifungal drug discovery. Zhonghua Bing Li Xue Za Zhi, 1992 Oct, 21(5), 275 - 7 {Histopathological and immunopathological studies on experimental pulmonary candidiasis}; Jiang XC; Experimental pulmonary candidiasis was produced by intratracheal inoculation of candida albicans in mice . The pathological changes could be divided into two stages, dominated by polymorphonuclear leukocyte infiltration and granuloma formation respectively . Preincubation of C . albicans with mouse anti-C . albicans antibody showed no obvious effect on pathological changes of the lungs as compared with the changes in the control mice, indicating that specific antibody did not play a crucial role in the defence mechanism of the lungs against C . albicans infection in normal mice . In the mice injected with antineoplastic drugs and hormones, abundant pseudohyphae were found in the lungs . Tissue necrosis and hemorrhage were obvious. Med Clin (Barc), 1992 Sep 12, 99(7), 241 - 3 {Monocytic dysfunction by opioid peptides in patients with major depression}; Castilla A et al.; BACKGROUND: Patients with depression present immunodepression and it has been proposed that, in these patients, endogenous opioid peptides may be mediators between the dysfunction of the central nervous system and immune alterations . METHODS: The function and the surface markers of monocytes were studied in 15 patients with major unipolar depression and in 24 healthy controls by biological trials of phagocytosis of Candida albicans and latex particles and immunofluorescence with monoclonal antibodies . RESULTS: Most of the patients studied (86%) presented monocytic dysfunction characterized by diminished phagocytic activity and a decrease in the expression of intermediate filaments of vimentin of the cytoskeleton and membrane molecules (CR1, receptor for the Fc fraction of the IgG and HLA DR antigens) . Incubation of the patients monocytes with naloxone led to the disappearance of monocytic alterations in most of the patients . CONCLUSIONS: Patients with major unipolar depression present a high opioid tone which has consequences in the function of the immune system. Pol Tyg Lek, 1992 Sep 7-14, 47(36-37), 812 - 3 {Aspergillosis of the lymphatic nodes}; Nowicka J et al.; The authors emphasize fungal lesions to the lymphatic nodes confirmed by the presence of Aspergillus flavus in blood and throat smear cultures (on Sabouraud's medium) and presence of A . flavus in cytological examination of biopsy from the lymphatic node, increased number of eosinophils in peripheral blood, and infiltration of eosinophils in bone marrow and lymphatic nodes . Aspergillosis coexisted with the infection with Candida albicans and S . aureus . The treatment of recurrent tonsillitis with antibiotics and also lowered granulocyte myeloperoxidase activity with increased production of O2 peroxide ion might predispose to such fungal infection. Mol Biol Evol, 1992 Sep, 9(5), 893 - 904 Molecular evolution of the fungi: human pathogens; Bowman BH et al.; The morphological, ecological, and clinical diversity among ascomycete fungi that are pathogenic to humans suggest that the potential for pathogenicity may have arisen multiple times within these higher fungi . We have obtained 18S ribosomal DNA sequences from a diverse group of human pathogenic fungi in order to determine their evolutionary origins . The fungi studied include a skin pathogen that is confined to humans (Trichophyton rubrum) and three systemic, facultative parasites that cause histoplasmosis (Histoplasma capsulatum), blastomycosis (Blastomyces dermatitidis) and coccidioidomycosis (Coccidioides immitis) in humans and other higher animals . Also included in our analysis are representatives of non-pathogenic fungi, as well as two opportunistic pathogens, Pneumocystis carinii and Candida albicans, that cause severe disease in immunocompromised individuals, especially those with AIDS . Two of the fungi we sequenced, T . rubrum and C . immitis, are limited to asexual modes of reproduction and therefore lack the sexual structures that are most useful for evolutionary comparison as well as being essential for classification among the higher fungi . Coccidioides immitis is particularly problematic owing to its contradictory and confusing asexual morphologies, which have caused it to be placed in three fungal classes and the protista . Our analysis shows that the specialized, superficial parasite and the systemic, facultative parasites, including C . immitis, are closely related ascomycetes, which clearly demonstrates the power of molecular characters to compensate for missing or confusing reproductive morphology . Analysis also shows that the opportunistic pathogens are more distantly related, with the likely explanation that pathogenicity has arisen more than once within the Ascomycetes. J Surg Res, 1992 Sep, 53(3), 263 - 7 Surgical trauma, Candida infection, and serum proteolytic activity; Miller RG et al.; Both surgical trauma and infection can disturb the proteinase to proteinase inhibitor balance in the circulation . We sought to assess the effect of Candida albicans infection (INFX) on postoperative mortality, to correlate mortality with total serum proteolytic activity (PA), and to assess the impact of exogenous proteinase inhibitors (PI) on this mortality . Mice underwent midline laparotomy (LAP) and immediate postoperative intravenous C . albicans infection . LAP + INFX shortened mean survival compared to INFX or LAP alone . Quantitative renal cultures confirmed that death in the LAP + INFX and INFX groups was due to Candida sepsis . PA was measured using an 125I-labeled protein assay, yielding micrograms of acid-soluble peptides/100 microliters of serum . In control, sham-operated, and LAP groups, PA averaged less than 9.0, and mortality was 0 . In INFX and LAP + INFX groups, PA averaged greater than 14.5 and mortality was high . To determine if high PA was related to high mortality, LAP + INFX mice were treated immediately preoperatively with a single dose of PI (1 mg alpha 1-proteinase inhibitor, 1 mg antithrombin, and 1000 KIU aprotinin) . Mean survival increased with PI treatment . In conclusion, the addition of Candida infection to surgical trauma hastened mean time to death . More rapid death correlated with elevated PA and may reflect systemic imbalance in the proteinase to proteinase inhibitor ratio in the circulation . PI improved survival, suggesting that proteinase inhibition may prove useful in the future in the treatment of fungal sepsis in surgical patients. J Neuropathol Exp Neurol, 1992 Sep, 51(5), 538 - 49 Biology of adult human microglia in culture: comparisons with peripheral blood monocytes and astrocytes; Williams K et al.; We have compared phenotypic and functional properties of surgically derived adult human microglia to autologous and allogenic peripheral blood-derived monocytes and to astrocytes derived from the same surgical resection . We found that microglia differed from peripheral blood monocytes with respect to adhesion properties and survival rates in vitro . Microglia, similar to resident macrophages in different tissues, expressed many but not all (CD4, Leu-M3, non-specific esterase) monocyte/macrophage associated markers tested, a pattern similar to that of terminally differentiated cells of this lineage . As with other human tissue macrophages, but in contrast to astrocytes, microglia did not undergo DNA synthesis in vitro, assessed using BrdU incorporation . Under basal culture conditions the majority of microglia of all morphologic subtypes (ameboid, bipolar, ramified) expressed MHC class II molecules; by flow cytometric analysis, mean fluorescence intensity of these cells was less than that of blood monocytes (relative to isotype control) . In vitro MHC class II antigen expression on microglia, under basal and interferon gamma activating conditions, was greater than on astrocytes . Freshly derived T cells cultured with 1-10% autologous microglia plus Candida albicans underwent active proliferation, indicating the functional capacity of the microglia to serve as antigen-presenting cells. Chest, 1992 Sep, 102(3), 953 - 4 Candida albicans purulent pericarditis treated successfully without surgical drainage; Karp R et al.; Cures of Candida pericarditis reported in the literature uniformly involved surgical drainage of the pericardial space . We report a patient with purulent pericarditis caused by Candida albicans who was treated successfully with antifungal chemotherapy combined with a single pericardiocentesis that did not completely evacuate the pericardial space . This case indicates that thoracotomy with surgical drainage of the pericardium is not mandatory for successful therapy of Candida pericarditis. J Invest Dermatol, 1992 Sep, 99(3), 331 - 6 Cultured human Langerhans cells process and present intact protein antigens; Cohen PJ et al.; Epidermal Langerhans cells (LC) undergo profound phenotypic and functional alterations when cultured for 2 to 3 d . To determine whether the in vitro culture of human LC modulates their capacity to process and present intact protein antigens, we compared the ability of freshly isolated LC (fLC) and cultured LC (cLC) to stimulate in vitro T-cell proliferative responses to recall antigens . We found that human fLC and cLC were able to process and present recall antigens to primed T cells, inducing significant proliferative responses . For tetanus toxoid and Candida albicans extract, T-cell proliferative responses at 6 d to antigen-pulsed fLC were slightly greater than responses to antigen-pulsed cLC . For live influenza A virus, the T-cell responses induced by antigen-pulsed cLC were comparable or slightly greater compared with fLC . Allogeneic T-cell proliferation for both LC preparations were also comparable . The exogenous pathway of antigen processing was demonstrated by chloroquine inhibition. J Infect Dis, 1992 Sep, 166(3), 587 - 97 Adherence of Candida albicans to tissues from mice with drug- or radiation-induced immunodeficiencies; Brawner DL et al.; Host factors that influence binding of Candida albicans to murine spleen, lymph node, and kidney were studied . Organs were harvested from BALB/cByJ and AKR/J mice immunocompromised by irradiation, cyclophosphamide, and cortisone acetate alone or in combination . Tissues from treated mice and untreated littermates were compared for their ability to bind C . albicans in ex vivo assays . Immunosuppressive regimens decreased yeast binding to splenic marginal zones, but when mice recovered for 5 days after treatment, adherence to spleen was similar to adherence in untreated littermates . Adherence to lymph node and kidney in treated mice was not different from binding to these tissues in untreated mice . Total serum immunoglobulin titers correlated with binding of yeast cells to mouse spleen . Blocking studies ruled out a mannosyl-fucosyl receptor-mediated binding . These results suggest that ex vivo adherence of C . albicans represents a host immune defense mechanism by which the immunocompetent host binds blood-borne yeast cells to host immune cells in reticuloendothelial organs to prevent dissemination to other organs. Infect Immun, 1992 Sep, 60(9), 3940 - 2 Inefficiency of in vivo candidacidal mechanisms in experimental subcutaneous infections with Candida albicans in mice; Sohnle PG et al.; A murine model of subcutaneous Candida albicans infections was used to evaluate host defenses against inocula of from 10(1) to 10(8) yeast cells . In these experiments, small inocula did not produce abscesses that drained to the skin surface, whereas larger ones did . Also, small numbers of organisms often remained at the infected sites for up to 21 days after inoculation with either small or large numbers of organisms . The data from these studies suggest that the in vivo candidacidal mechanisms in these infections are relatively inefficient and that they therefore may require some additional mechanism to control proliferation of the remaining organisms. Infect Immun, 1992 Sep, 60(9), 3586 - 95 Lymphokine-activated killer cell regulation of T-cell-mediated immunity to Candida albicans; Wei S et al.; Monocytes are important accessory cells in the activation of T cells for specific antigen recognition yet little is known of their regulation . We demonstrated here that interleukin-2 (IL-2)-induced human lymphokine-activated killer (LAK) cells can inhibit monocyte antigen presentation, depending on the state of differentiation of the monocytes . Adherent monocytes cultured for 4 days in medium or granulocyte-macrophage colony-stimulating factor (GM-CSF) were found to equally process and present intact Candida albicans to autologous Percoll gradient-isolated T cells, as measured by {3H}thymidine uptake . However, only the GM-CSF-cultured monocytes were functionally inhibited by autologous 4-day IL-2-induced LAK cells . Even soluble candidal cell wall mannoprotein antigens could not be presented by these monocytes after exposure to LAK cells . Pretreatment of these monocytes with LAK cells for 1 h, followed by subsequent removal of the nonadherent LAK cells, was sufficient to cause significant inhibition, with maximal inhibition observed after 4 h . Northern (RNA) blot analysis indicated that mRNA expression for IL-1 alpha and IL-1 beta in response to C . albicans stimulation was also down-regulated in GM-CSF-cultured monocytes exposed to LAK cells . Interestingly, freshly isolated, Percoll gradient-purified large granular lymphocytes did not suppress antigen presentation in GM-CSF-treated monocytes . Another important finding was the inability of LAK cells to suppress the ability of freshly isolated or gamma interferon-cultured monocytes, which are resistant to LAK cell-mediated lysis, to present antigen to T cells . In contrast, IL-3 was similar to GM-CSF in inducing LAK cell susceptibility in monocytes . Taken together, these results indicated that IL-2 can induce LAK cells to down-regulate antigen presentation function in a select set of monocytes that have been activated by colony-stimulating factor (GM-CSF and IL-3) but not by gamma interferon . LAK cells may therefore play an important role in regulation of monocytes and their function, depending on their differentiation state. Tohoku J Exp Med, 1992 Sep, 168(1), 1 - 9 Combination of conventional and endotoxin-specific limulus tests for measurement of polysaccharides in sera of rabbits with experimental systemic candidiasis; Miyazaki T et al.; Factor G, the coagulation enzyme from limulus amebocytes, is activated by (1-->3)-beta-D-glucan but not by endotoxin . The endotoxin-specific limulus test, which is devoid of factor G, reacts only with endotoxin . However, the conventional limulus test which includes factors G and C, reacts with not only endotoxin but also with (1-->3)-beta-D-glucan . In this study, the culture supernatant of Candida albicans in RPMI medium activated the conventional limulus test, but not the endotoxin-specific limulus test . All five rabbits inoculated intravenously with Candida albicans (1.0 x 10(7) CFU/rabbit) showed increased levels of reactivity with the conventional limulus test, whereas no elevation in the levels of the endotoxin-specific limulus test was observed in the sera of any infected rabbits . Only one serum sample from rabbit No . 5 on day 8 showed a positive Cand-tectest . The difference in the titers of the two limulus tests was suggestive of a diagnosis of Candida infection. Minerva Pediatr, 1992 Sep, 44(9), 455 - 7 {Vascular lesions in Candida albicans sepsis}; Vergara G et al.; In two premature newborns affected by candida sepsis we observed at ultrasonography alterations of the heart and of the anterior cerebral artery . These alterations suggest a cardiovascular involvement that is rarely reported in the literature as a complication of systemic candidiasis. Clin Exp Dermatol, 1992 Sep, 17 Suppl 1, 18 - 25 Influence of amorolfine on the morphology of Candida albicans and Trichophyton mentagrophytes; Muller J et al.; Amorolfine applied in concentrations of 0.1-100 micrograms/ml causes considerable damage to the ultrastructure of Candida albicans and Trichophyton mentagrophytes: electron-lucent areas appear in the cytoplasm; extracytoplasmic membrane vesicles are formed and deposited in the cell wall; starved fungal cells, with normal ultrastructure, can be found; lysed, dead cells demonstrate the process of severe ultrastructural damage; T . mentagrophytes cell walls especially increase in thickness . The extent of the damage caused by amorolfine is comparable to that produced by azole antifungals. J Antimicrob Chemother, 1992 Sep, 30(3), 313 - 20 In-vitro effects of liposome-encapsulated amphotericin B (AmBisome) and amphotericin B-deoxycholate (Fungizone) on the phagocytic and candidacidal function of human polymorphonuclear leucocytes; Pallister CJ et al.; Liposomal amphotericin B (AmBisome), at concentrations > or = 20 mg/L, and amphotericin B-deoxycholate (DC) (Fungizone), at concentrations > or = 1 mg/L, both caused a significant reduction in neutrophil uptake of Candida albicans blastospores following simultaneous addition of the drug with the blastospores . The reduction in uptake was seen also in tests in which blastospores were pre-treated with the drugs for 60 min, but was not detected in tests in which neutrophils were pre-treated for 60 min . Neither formulation affected neutrophil killing of C . albicans blastospores following simultaneous addition of the drug with the blastospores . However, previous treatment of the neutrophils with either formulation at a concentration of 20 mg/L led to enhanced killing of ingested blastospores . The results suggest that much higher concentrations of liposomal amphotericin B (AmBisome) are required to produce deleterious effects on neutrophil phagocytic function than with the conventional formulation of the drug. Prostaglandins Leukot Essent Fatty Acids, 1992 Sep, 47(1), 83 - 4 The role of eicosanoids in the kidney damage induced by Candida albicans; Kustimur S; A major target organ in generalized candidiasis is the kidney . The purpose of this study was to investigate the role of eicosanoids in the kidney infected by proteinase-positive and proteinase-negative Candida albicans . Prostaglandin (PG) E2-like activity was found to be significantly decreased while leukotriene (LT) C4-like activity increased within 10 days in the kidneys of mice infected with C . albicans . These results indicate that arachidonic acid metabolism is shifted to the lipoxygenase pathway and lipid peroxides, produced via this enzyme system may play an important role in the kidney damage induced by C . albicans. Mech Ageing Dev, 1992 Sep, 65(2-3), 157 - 65 Effect of physical activity stress on the phagocytic process of peritoneal macrophages from old guinea pigs; Ortega E et al.; The different stages of the phagocytic function in peritoneal macrophages from old guinea pigs (27 +/- 3-months-old) were studied before, immediately after and 24 h after being subjected to physical activity stress (swimming until exhaustion) which raised the blood levels of corticosterone . The phagocytosis of opsonized Candida albicans was stimulated immediately after physical activity . No modifications in adherence, chemotaxis, ingestion of inert particles, or microbicide capacity, measured by nitroblue tetrazolium (NBT) reduction, were found . At 24 h, when no stress could be shown by corticosterone analysis, the phagocytosis of opsonized C . albicans remained stimulated and chemotaxis was increased while ingestion of inert particles and microbicide capacity remained unchanged . The adherence, however, was at a smaller level . No correlations were found between the corticosterone levels and the status of the phagocytic process of peritoneal macrophages. Antimicrob Agents Chemother, 1992 Sep, 36(9), 1909 - 14 Chitin biosynthesis in Candida albicans grown in vitro and in vivo and its inhibition by nikkomycin Z; Chapman T et al.; An N-acetyl-D-{14C}glucosamine radiolabel incorporation assay has been used to monitor chitin biosynthesis in whole cells of Candida albicans both in vitro and in vivo in two different mouse infection models, one using the peritoneal cavity as a chamber in which to add and retrieve cells and the other using infected kidneys . Specific labeling of chitin in alkali-insoluble material was confirmed by chitinase digestion, analysis of acid hydrolysates, and the use of nikkomycin Z as a probe . Nikkomycin Z was shown to strongly inhibit chitin biosynthesis in C . albicans grown in vitro and in vivo in both models . This demonstrates that nikkomycin Z-susceptible chitin synthase activity is present in C . albicans when the fungus is in its pathogenic state in vivo . The limited use of nikkomycin as a therapeutic agent is discussed. Ophthalmology, 1992 Sep, 99(9), 1430 - 2 Atypical presentation of fungal dacryocystitis . A report of two cases; Purgason PA et al.; BACKGROUND: Candida albicans has only rarely been implicated in nasolacrimal duct obstruction . Its association with dacryoliths is well known, but it is unclear whether it is an etiologic factor or is present as a result of the obstruction . FINDINGS: The authors report 2 cases of fungal dacryocystitis that were not associated with dacryolith formation and where Candida species appear to be the primary etiologic agent . CONCLUSION: The possibility of a fungal infection should be considered in the evaluation of "routine" chronic dacryocystitis, particularly in the presence of corneal ulceration or postoperative endophthalmitis, as prompt initiation of appropriate therapy may be crucial. J Gen Microbiol, 1992 Sep, 138 ( Pt 9), 1901 - 11 Reduced azole susceptibility of oral isolates of Candida albicans from HIV-positive patients and a derivative exhibiting colony morphology variation; Gallagher PJ et al.; Approximately 50% (15/28) of a selection of oral isolates of Candida albicans from separate individuals infected with the human immunodeficiency virus (HIV) exhibited low susceptibility to ketoconazole as determined by hyphal elongation assessment . Nine of these isolates exhibited colony morphology variation or switching at 37 degrees C, of which six expressed low ketoconazole susceptibility . To determine whether colony morphology variation could give rise to derivatives with reduced azole susceptibility, several high-frequency switching variants of three HIV-patient isolates were recovered and assessed . All but one of the variants expressed similar azole susceptibility profiles to their respective parental strains . However, the C . albicans derivative 132ACR expressed significantly reduced susceptibility to ketoconazole in comparison to its parental strain 132A . In whole cells, on the basis of total growth the switched derivative 132ACR was markedly less susceptible than its parental isolate 132A to ketoconazole at 10 microM . A much smaller difference was observed with fluconazole at 10 microM, with the switched derivative 132ACR exhibiting a threefold lower susceptibility compared with the parental isolate 132A . The incorporation of {14C}acetate in control and azole-treated cells of both organisms was higher for the parental strain . When cell lysates of strain 132A and its derivative 132ACR were incubated with {14C}mevalonic acid and ketoconazole, the IC50 for 14C-label incorporation into C-4 demethyl sterols was fivefold higher for lysates of the switched derivative 132ACR compared with those of the parental strain 132A . With fluconazole the IC50 value for the derivative 132ACR was 25-fold higher than for strain 132A . The 14-sterol demethylase of the switched derivative 132ACR was possibly less sensitive to azole inhibition than that of the enzyme of strain 132A . These studies indicated that colony morphology variation in vitro can generate derivatives with stable, reduced azole susceptibility without prior exposure to azoles. J Gen Microbiol, 1992 Sep, 138 ( Pt 9), 1893 - 900 Isolation and characterization of a repeated sequence (RPS1) of Candida albicans; Iwaguchi S et al.; A repeated sequence, named RPS1, approximately 2 kb in size, is found mainly in chromosome 6, the second most variable chromosome among the eight chromosomes of Candida albicans . Most of the RPS1 units of chromosome 6 seem to be located within a single region of about 100 kb in strain FC18 . In both strains FC18 and NUM812, a part of RPS1 is apparently tandemly repeated . A unit of RPS1 has been cloned and sequenced . It consists of 2114 bp and has a GC content of 40 mol% . The repeat unit contains smaller repeats of about 80-170 bp which are called REP1, REP2, REP3, REP4 and REP5; REP2 is duplicated . The small repeats are classified into two groups by their homology . One comprises REP1, REP2 and REP5, and the other REP3 and REP4 . They are termed the REP1 and REP3 families, respectively . The two families both contain a common 29 bp sequence, called COM29 . The dispersed repetitive sequence RPS1 may be involved in chromosomal rearrangements and may in part explain chromosome polymorphism in C . albicans . The origin of RPS1 was not determined. J Infect Dis, 1992 Sep, 166(3), 668 - 73 Neutrophil oxidative burst in response to blastoconidia and pseudohyphae of Candida albicans: augmentation by granulocyte colony-stimulating factor and interferon-gamma; Roilides E et al.; The effects of granulocyte colony-stimulating factor (G-CSF) and interferon-gamma (IFN-gamma) on the oxidative burst of neutrophils (PMNL) in response to blastoconidia and pseudohyphae of Candida albicans were assessed and compared with those in response to N-FMLP . G-CSF enhanced oxidative burst, as measured by superoxide production, in response to both FMLP and opsonized blastoconidia . The enhancement of oxidative burst in response to FMLP was significantly greater (P = .004) than that in response to blastoconidia (65% and 39%, respectively) . G-CSF also enhanced oxidative burst in response to pseudohyphae . IFN-gamma enhanced oxidative burst in response to FMLP and opsonized blastoconidia by 53% and 50%, respectively . Moreover, IFN-gamma significantly enhanced oxidative burst in response to opsonized and nonopsonized hyphae by 86% and 65%, respectively . These results demonstrate that G-CSF and IFN-gamma enhance the oxidative burst of PMNL in response to both blastoconidia and pseudohyphae of C . albicans and suggest an immunomodulatory role of the two cytokines in the host defenses against this fungus. Infect Immun, 1992 Sep, 60(9), 3845 - 51 Mapping of Candida albicans oligomannosidic epitopes by using monoclonal antibodies; Trinel PA et al.; Six monoclonal antibodies (MAbs) from various laboratory sources (EB-CA1, EB-CA2, H5, AF1, C6, and 5B2), reacting with the polysaccharidic moieties of Candida albicans mannoproteins, were used for epitope mapping by an enzyme-linked immunosorbent assay (ELISA) with neoglycolipids and by Western blotting (immunoblotting) of a C . albicans germ tube extract . The ELISA involved neoglycolipids constructed from three families of oligomannosides released by sequential depolymerization of C . albicans phosphopeptidomannan by acid hydrolysis (NGLH), beta-elimination (NGLO), and acetolysis (NGLA) . All of the MAbs exhibited low reactivities against NGLO . MAbs EB-CA1, EB-CA2, and H5 reacted mainly against NGLA, and MAbs C6 and AF1 recognized mainly NGLH, whereas MAb 5B2 reacted with both families of neoantigens . When this method was compared with Western blotting, strong reactivity to NGLA was associated with the presence of epitopes shared by high-molecular-weight mannoproteins, whereas strong reactivity to NGLH was associated with a