Candida albicans

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 reactivity to a family of 14- to 18-kDa antigens . The reactivity of MAb 5B2 was associated with both high-molecular-weight mannoproteins and the 14- to 18-kDa antigens . In relation to the present knowledge about the structure of the C . albicans phosphopeptidomannan oligomannosidic repertoire, these results provide preliminary data concerning the molecular basis of the recognition of mannopyranosyl sequences by MAbs and their distribution among C . albicans mannoproteins.

Mycopathologia, 1992 Sep, 119(3), 147 - 56
Effect of nucleosides and nucleotides and the relationship between cellular adenosine 3':5'-cyclic monophosphate (cyclic AMP) and germ tube formation in Candida albicans; Sabie FT et al.; A yeast-mycelium (Y-M) transition in Candida albicans was induced by exogenous yeast extract, adenosine, adenosine 5'-monophosphate (AMP), adenosine 5'-diphosphate (ADP), adenosine 3':5' cyclic monophosphate (cAMP) and its analogue N6, O2'-dibutyryl adenosine 3':5'-cyclic monophosphate (dbcAMP) in defined liquid medium at 25 degrees C . Adenosine 5'-triphosphate (ATP) was found to delay germ tube formation in yeast cells, whereas the cAMP phosphodiesterase inhibitors, theophylline and caffeine, induced a Y-M transition . Intracellular and extracellular cyclic AMP levels increased during the yeast-mycelium transition and maximum levels of intracellular cyclic AMP coincided with maximum germ tube formation . Of the many inducers and inhibitors of germ tube and mycelium formation in C . albicans tested, including incubation at 37 degrees C or in the presence of 1.5 mM CaCl2, the calmodulin inhibitor calmidazolium (R24571) added together with CaCl2 induced the highest intra- and extracellular cyclic AMP levels . These results confirm the involvement of cyclic AMP in the yeast-mycelium transition of C . albicans.

Fertil Steril, 1992 Sep, 58(3), 511 - 7
Ethiodol oil contrast medium inhibits macrophage phagocytosis and adherence by altering membrane electronegativity and microviscosity; Johnson JV et al.; OBJECTIVE: To examine the effect of Ethiodol oil-soluble contrast medium and Sinografin aqueous-soluble contrast medium on macrophage function . After the observation that Ethiodol alters macrophage phagocytosis and adherence, we sought to determine the mechanism of action by which oil-soluble contrast medium alters the macrophage membrane . DESIGN: The P388D1 cell line was used as a consistent source of macrophages for all experiments . The uptake of 3H-labeled candida albicans was determined in macrophages exposed to 1:100, 1:400, or 1:800 dilutions of Ethiodol, Sinografin (S.R . Squibb, Princeton, NJ) or untreated media . To evaluate the macrophage adherence, 51Cr-labeled macrophages were exposed to the same dilutions of the contrast media . Specific membrane properties, Fc receptor levels, electronegativity, and microviscosity were assessed by flow cytometry after exposure to 1:100 dilutions of Ethiodol or Sinografin . RESULTS: Macrophage phagocytosis was decreased upon exposure to 1:100 and 1:400 dilutions of Ethiodol contrast medium, whereas adherence was reduced at the 1:100 dilution of Ethiodol . There was no effect of any dilution of Sinografin . There was a reduction in membrane electronegativity and microviscosity, but not Fc receptor levels, after exposure to a 1:100 dilution of Ethiodol . CONCLUSIONS: This study establishes a decrease in macrophage phagocytosis and adherence after exposure to Ethiodol oil-soluble contrast medium . We established that this alteration in membrane function is caused by a reduction of membrane negative surface charge and microviscosity . This may suggest a mechanism of action for the therapeutic effect of oil-contrast hysterosalpingograms in women with unexplained infertility.

J Bacteriol, 1992 Sep, 174(17), 5624 - 32
A temperature-regulated, retrotransposon-like element from Candida albicans; Chen JY et al.; A repetitive element was isolated from the genome of Candida albicans . This repetitive element, which we designated alpha, was localized to a 500-bp fragment of genomic DNA . The alpha element was dispersed in the genome and varied in copy number and genomic location in the strains examined . Analyses of various loci containing the alpha element identified a locus containing a composite element . This composite element consisted of two direct repeats of the alpha element separated by approximately 5.5 kb of DNA, a structural arrangement similar to that of retrovirus-like transposable elements . The flanking alpha elements of the composite structure were 388 bp in length and were identical in sequence . They were bounded by the nucleotides 5'-TG . .. . CA-3', which were part of a delimiting inverted repeat, a feature conserved in the long terminal repeats of retroviruses and retrovirus-like elements . As in retrovirus-like elements, the entire composite element, including the alpha elements, was transcribed into an approximately unit-length mRNA . The expression of this transcript was greatly increased when cells were grown at 25 versus 37 degrees C . As has been found in many retrotransposons, the composite element was flanked by a 5-bp duplication and varied in both copy number and genomic location in various strains . We conclude that the composite element is a retrotransposon-like element, and we have designated this element Tca1 . We suggest that Tca1 may be relevant to the genomic evolution of C . albicans and the pathogenic potential of the organism.

Am J Clin Nutr, 1992 Sep, 56(3), 599 - 603
Effects of oral soy phosphatidylcholine on phagocytosis, arachidonate concentrations, and killing by human polymorphonuclear leukocytes; Jannace PW et al.; A dietary supplement of linoleic acid (LA) as soy phosphatidylcholine (PC) or as triglyceride on polymorphonuclear leukocyte (PMNL) functions, arachidonate (AA) concentrations, AA release, and leukotriene B4 (LTB4) generation was studied in normal adults . Study 1: Eight subjects were fed PC (27 g) or placebo for 3 d in a blinded crossover experiment with PMNL assays at baseline and 4, 7, and 14 d . Study 2: Subjects were fed equal quantities of LA as PC (18 g, n = 8), safflower (SF, n = 4), or soybean oil (SY, n = 4) with PMNL assays at baseline and 48 h . Study 1: PC increased PMNL phagocytosis and killing of Candida albicans twofold (P less than 0.001) and PMNL phospholipid AA content threefold (P less than 0.001); AA release after Candida albicans stimulation increased 5.3-fold, correlating with PMNL killing (r = 0.932) and phagocytosis (r = 0.872) . Study 2: PC, but not SF or SY, produced changes similar to those of study 1 . With PMNL exposure to calcium ionophore A23187 or N-formyl-methionyl-leucyl-phenylalanine, PC increased LTB4 generation . Phospholipid LA, in contrast to triglyceride LA, enhanced PMNL phospholipid AA, phagocytosis, and killing.

J Marmara Univ Dent Fac, 1992 Sep, 1(3), 218 - 22
The prevalence of Candida albicans in complete denture and removable partial denture wearers: a comparative study; Alkumru HN et al.; In this study, 60 complete denture wearers, 53 removable partial denture wearers and 50 dentate subjects were examined to determine the Candidal carrier state . The influence of local factors such as denture type, smoking habits and sex on Candidal carrier rate were investigated . Wearing complete or removable partial denture was determined as an important factor increasing Candidal carrier rate . Cigarette smoking is another factor which increases Candidal growth in complete denture and removable partial denture wearers . In contrast to denture wearers Candidal carrier rate was considerably less on dentate smokers . Candidal colonization rate was found to be higher on the dorsum of the tongue . This suggests that the tongue is the primary oral reservoir of Candida albicans in the mouth.

Biochem Biophys Res Commun, 1992 Aug 31, 187(1), 480 - 7
Isolation and characterization of a 25 kDa antifungal protein from flax seeds; Borgmeyer JR et al.; We have purified a 25 kDa protein from flax seeds to homogeneity by polyethyleneimine precipitation, ammonium sulfate precipitation, chitin extraction, Mono S cation exchange and C18 reversed phase column chromatographies . The purified protein strongly inhibited the growth of the agronomically important pathogen Alternaria solani, the causative agent of tomato early blight and in synergy with nikkomycin Z strongly inhibited the human pathogen Candida albicans . Amino terminal sequence analysis of the purified protein indicated that it has a high degree of homology to other reported pathogenesis-related antifungal proteins.

J Immunol Methods, 1992 Aug 30, 153(1-2), 167 - 72
A comparison of specific IgG antibody levels to the cell wall mannan of Candida albicans in normal individuals and in patients with primary antibody deficiency; Faux JA et al.; An enzyme-linked immunosorbent assay (ELISA) has been developed to measure specific IgG antibody to the polysaccharide, cell wall mannan of Candida albicans (mannan) . The results were expressed as arbitrary units/ml, with an inter- and intra-assay coefficient of variation of 7-11% . In establishing normal ranges we found that specific IgG to the mannan increased with age, with 18% of healthy children aged 3-10, 48% of healthy children aged 11-19 and 76% of an adult donor population having specific IgG antibody to mannan (greater than 30 U/ml) . We have compared these normal ranges, with a group of patients with primary antibody deficiency (PAD) . None of the 23 patients with PAD, which included common variable immunodeficiency, IgG subclass deficiency, and selective IgA deficiency, had titres greater than 30 U/ml . The patients with PAD had significantly lower levels of specific IgG anti-mannan antibody (median 9 U/ml) compared to healthy children aged 11-19 (median 26 U/ml) or adults (median 58 U/ml) (p = less than 0.001) but not children aged 3-10, (median 1 U/ml) (p = 0.08).

Infect Immun, 1992 Aug, 60(8), 3087 - 91
Cell extracts of Candida albicans block adherence of the organisms to endothelial cells; Edwards JE Jr et al.; Cell extracts of Candida albicans were fractionated by concanavalin A affinity chromatography . Eluted mannosylated proteins (fraction II) and nonbinding, nonmannosylated proteins (fraction I) were collected and assayed directly for inhibition of adherence of C . albicans to endothelium . Fraction II blocked blastospore adherence to endothelial cells . Fraction I blocked both blastospore and germ tube adherence to endothelial cells . Monoclonal antibody OKM-1 (anti-CR3) and an anti-C . albicans monoclonal antibody, CA-A (anti-CR2), reacted in Western blots with proteins from fraction I, suggesting the presence of the CR2- and CR3-like proteins that have been previously identified on C . albicans germ tubes.

Am J Dis Child, 1992 Aug, 146(8), 924 - 9
Patterns of infection after pediatric liver transplantation; George DL et al.; OBJECTIVE . To characterize the patterns of infection that occur after orthotopic liver transplantation in children . DESIGN . Inception cohort, retrospective . SETTING . Referral center for liver transplantation, university hospital . PATIENTS . Thirty-six consecutive children who underwent orthotopic liver transplantation and who survived for at least 48 hours after transplantation . INTERVENTIONS . None . MEASUREMENTS AND RESULTS . Twenty-six (72%) of the children had at least one infection, and infection caused four deaths . More infections occurred when prophylactic antilymphocyte antibodies were given than when they were not given (2.9 vs 1.0 infections per transplant) . The risk of infection was greatest during the first 2 weeks after orthotopic liver transplantation . Most infections were caused by bacteria (52 cases), followed by viruses (16 cases) and fungi (11 cases) . Bacteria were the most common pathogens during all periods, except the third and fourth weeks, when viruses predominated . The most common primary sites of bacterial infection were abdomen (15 cases), bloodstream (15 cases), and surgical wound (10 cases); the most frequent isolates were aerobic gram-negative bacilli (48% of isolates) and enterococci (19%) . Cytomegalovirus was the most common viral pathogen (seven cases), and Candida albicans caused all fungal infections . Fungal infections were significantly associated with systemic antibiotic therapy and abdominal complications . CONCLUSIONS . Characteristic patterns of infection occur after pediatric orthotopic liver transplantation, and knowledge of these patterns is likely to result in improved care for transplant recipients.

P R Health Sci J, 1992 Aug, 11(2), 77 - 80
Extraction and purification of a catalase from Candida albicans; Tosado-Acevedo R et al.; Candida albicans yeast cells H317 were grown to mid-log phase, mechanically disrupted and the resulting crude extract clarified by centrifugation . This catalase rich fraction (1.26 x 10(-4) units/ml) was fractionated by liquid phase isoelectric focusing in a pH gradient ranging from 3 to 10 using the Rotofor Isoelectric Focusing Preparative Cell . After isoelectric separation, fractions containing catalase activity were focused between pH 6.7 and 9.3 . Active fractions were pooled and re-focused . After the second fractionation, catalase activity increased to 1.52 x 10(-2) units/ml and was restricted to fractions ranging from pH 7.6 to 8.8 . To this point a 121 fold purification was achieved . Native polyacrylamide gel electrophoresis analysis of active fractions revealed a band migrating between 272,000 and 132,000 daltons which showed catalase activity . Purification of C . albicans catalase will allow us to evaluate its potential role in protecting this opportunistic pathogen from products of the oxidative burst . Antibodies generated against the catalase provide means for the evaluation of neutralizing fungal defenses against products of the oxidative burst during phagocytosis.

Clin Exp Allergy, 1992 Aug, 22(8), 756 - 61
IgE antibodies to Pityrosporum orbiculare and Staphylococcus aureus in patients with very high serum total IgE; Nordvall SL et al.; Serum IgE antibodies were detected with the radioallergosorbent test (RAST) to a panel of allergens which included Pityrosporum orbiculare, Candida albicans, Trichophyton rubrum, Cladosporium herbarum, Staphylococcus aureus, animal dander, deciduous tree pollens, grass pollens and foods in 81 consecutive patients with total IgE greater than or equal to 3000 kU/l . Data on atopic and infectious disease characteristics were collected by a questionnaire . IgE antibody concentrations to P . orbiculare were significantly higher than to the other fungi and of the same magnitude as those to animal danders and pollens . High levels of P . orbiculare IgE antibodies were associated with current eczema, especially when it was the only atopic manifestation and demanding specialist care . IgE antibodies to P . orbiculare had the best explanatory value for current eczema in logistic regression analysis . Head-neck-face dermatitis was also associated with high levels of specific IgE to the yeast . IgE antibodies to S . aureus were detected in few patients and at low concentrations . Six patients had a history of systemic staphylococcal infections and presented a clinical picture, which was very similar to the hyperimmunoglobulinaemia E syndrome . Among the six were the two cases with the highest levels of IgE antibodies to S . aureus . The demonstration of high levels of IgE antibodies to P . orbiculare, which is a major part of human normal skin microflora, suggests that allergy to this yeast plays an important pathogenic role in eczema.

J Clin Microbiol, 1992 Aug, 30(8), 1976 - 81
Collaborative investigation of broth microdilution and semisolid agar dilution for in vitro susceptibility testing of Candida albicans; Shawar R et al.; A study was performed in two laboratories to evaluate the effect of growth medium and test methodology on inter- and intralaboratory variations in the MICs of amphotericin B (AMB), flucytosine (5FC), fluconazole (FLU), itraconazole (ITRA), and the triazole Sch 39304 (SCH) against 14 isolates of Candida albicans . Testing was performed by broth microdilution and semisolid agar dilution with the following media, buffered to pH 7.0 with morpholinepropanesulfonic acid (MOPS): buffered yeast nitrogen base (BYNB), Eagle's minimal essential medium (EMEM), RPMI 1640 medium (RPMI), and synthetic amino acid medium for fungi (SAAMF) . Inocula were standardized spectrophotometrically, and endpoints were defined by the complete absence of growth for AMB and by no more than 25% of the growth in the drug-free control for all other agents . Comparative analyses of median MICs, as determined by each test method, were made for all drug-medium combinations . Both methods yielded similar (+/- 1 twofold dilution) median MICs for AMB in EMEM and RPMI, 5FC in all media, and FLU in EMEM, RPMI, and SAAMF . In contrast, substantial between-method variations in median MICs were seen for AMB in BYNB and SAAMF, FLU In BYNB, and ITRA and SCH in all media . Interlaboratory concordance of median MICs was good for AMB, 5FC, and FLU but poor for ITRA and SCH in all media . Endpoint determinations were analyzed by use of kappa statistical analyses for evaluating the strength of observer agreement . Moderate to almost perfect interlaboratory agreement occurred with AMB and 5FC in all media and with FLU in EMEM, RPMI, and SAAMF, irrespective of the test method . Slight to almost perfect interlaboratory agreement occurred with ITRA and SCH in EMEM, RPMI, and SAAMF when tested by semisolid agar dilution but not broth microdilution . Kappa values assessing intralaboratory agreement between methods were high for 5FC in all media, for AMB in BYNB, ENEM, and RPMI, and for FLU in EMEM, RPMI, and SAAMF . One laboratory, but not the other, reported substantial to almost perfect agreement between methods for ITRA, and SCH in EMEM, RPMI, and SAAMF . Both laboratories reported poor agreement between methods for the azoles in BYNB . Discrepancies noted in azole-BYNB combinations were largely due to the greater inhibitory effect of these agents in BYNB than in other media . These results indicate that the semisolid agar dilution and broth microdilution methods with EMEM or RPMI yield equivalent and reproducible MICs for AMB, 5FC, and FLU but not ITRA and SCH.

Cell Mol Biol, 1992 Aug, 38(5), 505 - 11
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 antimicrobial/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 ug/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 ug/ml and 0.98 ug/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.

Res Commun Chem Pathol Pharmacol, 1992 Aug, 77(2), 249 - 52
Direct membrane damage and miconazole lethality; Beggs WH; Physicochemical membrane damage is presumably the cause of growth phase-dependent lethal miconazole action . In support of this, we showed that as stationary phase inoculum cells of Candida albicans progress into early logarithmic phase, susceptibilities to lethal action and to miconazole-induced release of K+ increase together.

Pharmazie, 1992 Aug, 47(8), 582 - 4
Oxidation of brefeldin A; Proksa B et al.; Oxidation of the macrolide antibiotic brefeldin A with pyridinium chlorochromate adsorbed on alumina afforded {6S, 10E, 11aS, 14E}-6-methyl-2,3,6,7,8,9,11a,12-octahydro-4 H-cyclopent{f}oxacyclotridecin-1,4,13-trione together with 13-oxobrefeldin . These compounds showed higher cytotoxic activity on P388 leukemia cells than brefeldin A, brefeldin A-1,13-diacetate, brefeldin A-13-acetate, tetrahydrobrefeldin or tetrahydrobrefeldin-1,13-dione . 13-Oxobrefeldin exceeded brefeldin A in antifungal activity on Candida albicans.

Curr Genet, 1992 Aug, 22(2), 93 - 100
DNA translocations contribute to chromosome length polymorphisms in Candida albicans; Thrash-Bingham C et al.; Rotating-gel electrophoresis and DNA hybridization were used to compare the electrophoretic karyotype of six Candida albicans isolates . The hybridization pattern for 22 cloned sequences, including eight previously unmapped genes, indicates that there are eight pair of homologous chromosomes in each strain . However, since homologous chromosomes can differ in length, it is possible to resolve more than eight bands in some strains . The mapping data demonstrate that linkage groups are generally conserved suggesting that, in spite of gross karyotype differences, there is an underlying similarity in the genome organization of different isolates . The hybridization data also provide direct evidence that DNA translocations and reciprocal translocations contribute to chromosome length polymorphisms in C . albicans.

Arzneimittelforschung, 1992 Aug, 42(8), 1049 - 52
Subcellular distribution and antifungal effects of fluconazole in human phagocytic cells . Demonstration of the antifungal agent in neutrophil polymorphonuclear leucocytes and monocytes by autoradiography and electron micrography; Wildfeur A et al.; Electron microscopic autoradiography was used to demonstrate the presence of {3H} fluconazole (CAS 86386-73-4) in neutrophils and monocytes isolated from volunteers . Quantitative analysis of the autoradiographs showed significant accumulation of fluconazole in both phagocytic cells . The distribution of fluconazole was equal in the different intracellular compartments such as cytoplasm and nucleus . Fluconazole (20 micrograms/ml) induced ultrastructural changes in Candida albicans cells which had been phagocytized by neutrophils or monocytes (macrophages) in vitro . Particularly, changes in the plasma membrane and in the cytoplasmic structure of the intraphagocytic yeast cells were observed electron microscopically.

Antimicrob Agents Chemother, 1992 Aug, 36(8), 1779 - 81
Effects of squalene epoxidase inhibitors on Candida albicans; Georgopapadakou NH et al.; The relationship between sterol biosynthesis inhibition, membrane integrity, and cell growth inhibition in Candida albicans was examined for five squalene epoxidase inhibitors . The compounds were the thiocarbamates tolnaftate and tolciclate and the allylamines naftifine, terbinafine, and SDZ 87-469 . All compounds inhibited sterol biosynthesis, with the concentrations that caused a 50% decrease in the total sterol-to-squalene ratio ranging from less than or equal to 0.01 microM for terbinafine and SDZ 87-469 to 500 microM for tolnaftate . At 100 microM, the compounds also caused up to a 30% release of intracellular {14C}aminoisobutyric acid . With terbinafine and SD2 87-469, aminoisobutyric acid release further increased in cells grown at concentrations that inhibited ergosterol biosynthesis . It is suggested that inhibition of ergosterol synthesis may render the C . albicans membrane susceptible to further damage, including direct damage from squalene epoxidase inhibitors.

Acta Ophthalmol (Copenh), 1992 Aug, 70(4), 528 - 9
Fluconazole in the treatment of candida albicans endophthalmitis; Urbak SF et al.; A 29-year-old former drug addict with candida albicans endophthalmitis determined by cultivation was treated with vitrectomy and systemic fluconazole . The infection resolved completely and the patient recovered a visual acuity of 6/6 . Fluconazole was well tolerated and a high concentration was found in the vitreous cavity.

Immun Infekt, 1992 Aug, 20(4), 134 - 5
{In vitro proliferation of human bone marrow cells--inhibition by components of Candida albicans}; Diezel W et al.; Candida albicans (CA) components influence the proliferation of human bone marrow cells in vitro (colony-forming assay) . Number of colonies per 10(5) bone marrow cells after cultivation with rHuGM-CSF (maximal plateau colony formation): 46.2 +/- 9.1 (n = 6); after cultivation with rHuGM-CSF in combination with CA proteins: 0.05 mg protein/ml: 33.4 +/- 4.6 (n = 3); 0.10 mg protein/ml: 20.8 +/- 3.6 (n = 3).

Gesundheitswesen, 1992 Aug, 54(8), 400 - 5
{Examination and evaluation of the hygiene status of natural peloids for human medical use}; Eichelsdorfer D; For curative treatment in German spas, different muds for medical mud-baths and mud-packs are also used besides mineral springs . Muds of this kind are known by the collective term of "peloids" . According to the "Definitions of the German Health Resorts Association", peloids are classified by a new geological-genetic system . After discussing hygienic aspects and problems of diverse therapeutic applications using peat, marine muds or fango, standardized methods for microbiological examinations are described . For the microbiological control parameters E . coli, Coliform organisms, Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans, suggested values and threshold values are given in detail.

J Dent, 1992 Aug, 20(4), 250 - 4
Rat palatal histology related to denture-like appliances; Jennings KJ et al.; Two designs of palatal denture-like appliance were fitted to rats . Tooth- and tissue-borne appliances caused changes in epithelial thickness and keratin thickness, but these varied with anatomical site and type of appliance . A single inoculation of Candida albicans at the time of insertion of the appliance failed to establish infection consistently . Debris accumulation under the appliances was a problem which will restrict long-term studies with this model.

Blood, 1992 Aug 1, 80(3), 788 - 94
Differentiation and functional activity of human eosinophilic cells from an eosinophil HL-60 subline: response to recombinant hematopoietic growth factors; Fabian I et al.; We studied the effect of hematopoietic growth factors (granulocyte-macrophage colony-stimulating factor {GM-CSF}, granulocyte {G}-CSF, interleukin (IL)-1, IL-3, IL-5, IL-6, and macrophage {M}-CSF) on differentiation and functional activity of human eosinophilic HL-60 cells (Eos-HL-60) and compared them with effects on parental HL-60 promyelocytic leukemia cells . Purified biosynthetic GM-CSF and IL-5 enhanced cell proliferation and induced eosinophilic differentiation in the eosinophilic subline in both liquid and agar cultures . IL-3 and IL-6 stimulated cell proliferation but had no effect on cell differentiation, whereas IL-1 and G-CSF affected neither differentiation nor proliferation of Eos-HL-60 cells under the conditions tested . GM-CSF-, IL-3-, and IL-5-treated Eos-HL-60 cells showed increased O2- production in response to phorbol esters (PMA), enhanced phagocytosis of Candida albicans, and release of the enzymes arylsulfatase, beta-glucuronidase and eosinophil peroxidase (EPO) . The degranulation of eosinophils induced by GM-CSF, IL-5, and IL-3 may have relevance to the potential clinical toxicity of these hematopoietins, which also stimulate eosinophilopoiesis . G-CSF had no effect on enzyme release, oxidative metabolism, or phagocytic capacity of Eos-HL-60 cells . IL-5 did not affect proliferation, differentiation, or enzyme release in promyelocytic HL-60 cells . These results indicate the specificity of IL-5 for the eosinophil lineage, confirm the effects of GM-CSF and IL-3 on eosinophilopoiesis and mature eosinophil function in a model system, and indicate the absence of G-CSF and IL-1 stimulation of eosinophils . The Eos-HL-60 line is a useful model for studying human eosinophil responses to cytokines.

Acta Derm Venereol, 1992 Aug, 72(4), 241 - 4
The fate of individual organisms during clearance of experimental cutaneous Candida albicans infections in mice; Sohnle PG et al.; A mouse model of acute cutaneous Candida albicans infections was used to study the manner in which these infections are cleared . Results of histological examination were correlated with determinations of the viability by acridine orange staining of superficial C . albicans pseudohyphae retrieved from the surface of the infected skin . The number of organisms retrieved from the skin surface was highest on the third and fourth day after inoculation, a finding which appeared to relate to a loss of Candida foci observed histologically to occur after the second day . Viability was high (approximately 80%) for at least 1-2 days after the organisms were seen histologically to have become associated with neutrophils and extruded from the stratum Malpighi into the stratum corneum; however, at later time points (fourth and fifth day after inoculation), the viability of the retrieved organisms did decline . Pseudohyphae germinated in vitro and applied to the skin of mice were found to be non-viable when retrieved 24 h later . These data suggest that the microbicidal processes of neutrophils may not be required for resolution of these infections . They are most consistent with clearance through an epidermal proliferative response which relocates the infecting organisms to a very superficial site, from which they can be either lost in a viable state, or subjected to killing by other factors at the skin surface.

Antimicrob Agents Chemother, 1992 Aug, 36(8), 1626 - 9
Increased sensitivity of Candida albicans cells accumulating 14 alpha-methylated sterols to active oxygen: possible relevance to in vivo efficacies of azole antifungal agents; Shimokawa O et al.; The sensitivity of Candida albicans cells to killing by hydrogen peroxide was found to increase markedly when they were grown in the presence of sub-growth-inhibitory concentrations of the azole drug clotrimazole (CTZ) . A superoxide anion-generating system consisting of xanthine and xanthine oxidase also killed such CTZ-treated cells more efficiently than control cells, but this seemed to be accounted for by hydrogen peroxide secondarily formed from superoxide anion as judged by the effect of catalase and superoxide dismutase . The increased sensitivity to hydrogen peroxide was considered to be attributable to the inhibition of 14 alpha-demethylation of ergosterol biosynthesis by CTZ, since a 14 alpha-demethylation-deficient mutant of C . albicans exhibited a similar phenotype . It is suggested that the in vivo efficacy of azole antifungal agents against C . albicans infection is at least partially due to the sensitization of the fungal cells to the oxygen-dependent microbicidal system of the phagocyte.

FEMS Microbiol Immunol, 1992 Aug, 4(6), 335 - 43
Stimulation of human B cells specific for Candida albicans for monoclonal antibody production; Davenport C et al.; The stimulation and immortalisation of human peripheral blood B lymphocytes specific for Candida albicans antigen were investigated . An in vitro immunisation system was employed which involved pretreatment of mononuclear cells with L-leucyl L-leucine methyl ester which removes the suppressive effects of CD8+ T cells, NK cells and monocytes . The remaining cells, CD4+ T cells, B cells and dendritic cells, were cultured with antigen and a mixture of cytokines . A mixture of IL-2, -4 and -6 was found to be optimal for antibody production as determined by an Elispot assay . Transformation of the activated B cells by Epstein Barr virus was found to be optimal after 2 days and lines secreting anti-Candida antibodies were established . These lines could form the basis for specific monoclonal antibody production by generating hybridomas, or by a newly described technique whereby cDNA encoding antibody Fab regions is transferred into phage display libraries . The overall strategy might be generally applicable for the generation of human monoclonal antibodies to infectious agents.

Pediatr Dent, 1992 Jul-Aug, 14(4), 236 - 9
The detection of oral Candida in pediatric leukemia patients; Stinnett EA et al.; Among leukemia patients, a significant number of deaths are due to Candida septicemia, many of which are associated with previous oral infections . Oral candidiasis detection methods vary, and the relationship between oral candidiasis and Candida colonization (CC) is not well defined . The main objectives of this study were to compare the incidence of CC in a healthy and leukemic population, and also to evaluate the efficacy of three simple and inexpensive methods of detecting oral CC in predicting the occurrence of oral candidiasis . A secondary objective was to portray speciation in the examined populations . Forty-two pediatric leukemia patients and 42 healthy, age-, race-, and gender-matched control patients participated in this study . The three methods of detection were cytological examination of the oral mucosa, and direct culture methods from mucosal smears using Sabouraud's dextrose agar (Becton Dickinson Microbiology Systems, Cockeysville, MD) and Oricult-N (Orion Diagnostica, Espoo, Finland) . This study demonstrated an increased prevalence of CC in pediatric leukemia patients with the direct culture method detecting CC in a significantly greater proportion of the population (Oricult-N,P = 0.034; Sabouraud's dextrose agar, P = 0.0036) . Candida albicans was the predominant species . Further study is needed to determine the clinical significance of oral CC and its relationship to oral candidiasis and systemic infection in pediatric leukemia patients.

Biochim Biophys Acta, 1992 Jul 9, 1127(1), 1 - 14
Emerging role of lipids of Candida albicans, a pathogenic dimorphic yeast; Mishra P et al.; It is clear that C . albicans lipids have gained tremendous importance in recent years . In addition to being a barrier for entrance of various metabolites, it also provides the site of action for the synthesis of enzyme(s) involved in cell wall morphogenesis and antifungal action . While alterations in lipid composition during a yeast to mycelia transition have been observed, in most of the studies, lipid fluctuations reported could have been due to various environmental factors involved in the induction of morphogenesis {4,5} . A clear understanding of lipid biosynthesis and metabolic blocks due to antifungal action is likely to shed further light on selective interactions of antifungals . Despite the multifacet role of lipids in various functions of this pathogenic yeast, their exact involvement is poorly understood . The situation is little better with regard to ergosterol and its metabolism . Ergosterol is, indeed, important for anti-candidal activity and appears to be involved in the morphogenesis of C . albicans . The fluctuation in phospholipid composition have led to altered properties of plasma membrane namely, membrane fluidity, transport activities and drug sensitivity, which suggest that-a critical level of individual phospholipid is important for proper functioning of the plasma membrane . What the exact role is of individual phospholipid is far from clear . Many unanswered questions relating to the role of PI and sphingomyelin in signal transduction, involvement of phospholipases in the maintenance of phospholipid composition, and role of lipid transfer proteins in assembly and asymmetry of lipids are some aspects which merit further work.

Carbohydr Res, 1992 Jul 2, 231, 105 - 16
Structure of the D-mannan of the pathogenic yeast, Candida stellatoidea ATCC 20408 (type II) strain, in comparison with that of C . stellatoidea ATCC 36232 (type I) strain; Kobayashi H et al.; Acid treatment of the cell-wall D-mannas of Candida stellatoidea strains ATCC 36232 (Type I, A3 strain) and ATCC 20408 (Type II, A2 strain) gave (1----2)-linked beta-D-manno-oligosaccharides (dp 2-5), whereas treatment with alkali gave the (1----2)-linked alpha-D-mannobiose . Conventional acetolysis of the acid- and alkali-treated D-mannan of the A3 strain gave oligosaccharides consisting of (1----2)- and (1----3)-linked alpha-D-mannopyranose residues, similar to those of Candida albicans serotype B strain . Mild acetolysis of the acid- and alkali-treated D-mannan of the A2 strain gave higher oligosaccharides that were digested by the Arthrobacter GJM-1 strain exo-alpha-D-mannosidase . The results of 1H- and 13C-NMR analyses indicated this D-mannan to contain branches with the following structures: beta-D-Manp-(1----2)-alpha-D-Manp-(1----2)-alpha-D-Manp++ +-(1----2)-alpha-D-Manp- (1----2)-D-Man, beta-D-Manp-(1----2)-beta-D-Manp-(1----2)-alpha-D-Manp -(1----2)- alpha-D-Manp-(1----2)-D-Man, and beta-D-Manp-(1----2)-beta-D-Manp-(1----2)-beta- D-Manp-(1----2)-alpha-D-Manp-(1----2)-alpha-D-Manp-(1- ---2)-alpha-D-Manp- (1----2)-D-Man, in common with the D-mannans of C . albicans serotype A strains.

South Med J, 1992 Jul, 85(7), 773 - 4
Candidal endophthalmitis after lithotripsy of renal calculi; Greenwald BD et al.; Candidal endophthalmitis is most commonly due to hematogenous seeding of the eye by Candida albicans . Although it is most often seen as a manifestation of disseminated candidiasis in patients who are seriously ill, other patients may have candidal endophthalmitis as the only evidence of fungal infection . We have presented a case of endophthalmitis due to C albicans in a patient who had bilateral renal calculi and who had received multiple antibiotics and extracorporeal shock wave lithotripsy.

Gene, 1992 Jul 1, 116(1), 51 - 7
Isolation, characterization, and sequencing of Candida albicans repetitive element 2; Lasker BA et al.; A 1059-bp Sau3A fragment, designated Candida albicans repetitive element 2 (CARE-2), was isolated from the genome of the pathogenic yeast, C . albicans . CARE-2 DNA was detected on several C . albicans chromosomes separated by transverse alternating-field electrophoresis . A high degree of interstrain variation in the pattern of hybridizing bands were observed by Southern blot analysis, with a minimum of 10-14 copies of CARE-2 per strain . A low frequency of new CARE-2 polymorphisms was observed over time for three strains grown at 25 degrees C or 37 degrees C . No new CARE-2 polymorphisms were observed from two naturally occurring switch phenotypes . To localize repeated DNA, oligodeoxyribonucleotide probes, each representing a different region of CARE-2, were hybridized to genomic blots . A lower number of copies were observed 5' and 3' to a 600-bp region of CARE-2 . Nucleotide (nt) sequence analysis of CARE-2 DNA shows the element is characterized by six perfect direct repeats 6 bp in length and shows no significant DNA similarity with any known nt sequence.

Am J Med, 1992 Jul, 93(1), 29 - 34
Nonresolving pneumonia in steroid-treated patients with obstructive lung disease; Rodrigues J et al.; PURPOSE: To review autopsy-proven cases of opportunistic pneumonia and determine how many of these patients had received corticosteroid therapy for obstructive lung disease in order to define whether this therapy was the major risk factor predisposing to infection . PATIENTS AND METHODS: All autopsies performed at Winthrop-University Hospital over a 5-year period were reviewed, and 30 cases of opportunistic pneumonia were identified . In eight of 30 cases, corticosteroid therapy for chronic obstructive pulmonary disease (COPD) was the only identifiable risk factor for opportunistic infection . The other 22 patients had other well-defined risk factors for infection . Chart review of the eight patients with COPD was undertaken to define the clinical features of their infections . RESULTS: All eight patients had a progressive multilobar pneumonia that failed to resolve, either clinically or radiographically, despite the use of multiple broad-spectrum antibiotics . In four cases, the infection was community-acquired, while in the other four cases, it was nosocomial in origin . Despite the presence of a nonresolving pneumonia, opportunistic infection was generally not considered as a diagnostic possibility, with only one case being correctly diagnosed antemortem . Autopsy examination documented Aspergillus species as being responsible for six episodes of pneumonia, Candida albicans accounting for one episode, and cytomegalovirus accounting for one episode . CONCLUSION: Based on this experience, it is clear that corticosteroid therapy of COPD can lead to opportunistic pulmonary infection, in or out of the hospital . This diagnosis should be considered when patients receiving this therapy develop a pneumonia that fails to respond to broad-spectrum antibiotics.

J Bacteriol, 1992 Jul, 174(14), 4807 - 10
Candida albicans produces a cystatin-type cysteine proteinase inhibitor; Tsushima H et al.; A cysteine proteinase inhibitor was found in culture media of Candida albicans . Purification to homogeneity of the inhibitor was performed by carboxymethyl-papain-Sepharose affinity, DE-52 ion-exchange, and reverse-phase high performance liquid chromatographies . The purified inhibitor had an M(r) of 15 kDa and a pI of 4.9 . It was more stable to heat and pH than most proteins . The N-terminal sequence of the first 30 residues demonstrated high similarity with that of human cystatin A . Thus, C . albicans cysteine proteinase inhibitor seems to belong to the cystatin superfamily . The inhibitor activity of the yeast cellular form was 4.0 times higher than that of the hyphal cellular form in 7-day culture media . It is suggested that the inhibitor has regulatory functions similar to those of its counterpart proteinases in the invasion of host cells.

Mol Cell Biol, 1992 Jul, 12(7), 2997 - 3005
Transcription of the gene for a pepsinogen, PEP1, is regulated by white-opaque switching in Candida albicans; Morrow B et al.; Cells of Candida albicans WO-1 spontaneously switch between a white and opaque CFU, and this phase transition involves a dramatic change in cellular phenotype . By using a differential hybridization screen, an opaque-specific cDNA, Op1a, which represents the transcript of a gene regulated by switching, has been isolated . The gene for Op1a is transcribed by opaque but not by white cells . The nucleotide sequence of the Op1a cDNA reveals over 99% base homology with an acid protease gene of C . albicans, and the predicted amino acid sequence demonstrates that the product of this gene is a member of the family of pepsinogens, which possess a hydrophobic leader sequence for secretion and two catalytic aspartate domains . Southern blots of both genomic DNA digested with 14 different endonucleases and electrophoretically separated chromosomes were probed with the Op1a cDNA . No polymorphisms were detected in either case between white and opaque cells, suggesting that no genomic reorganization occurs in the proximity of the gene during the white-opaque transition . Although transcription of Op1a correlates with the high levels of extracellular protease activity in opaque cell cultures and the absence of activity in white cell cultures, stimulation of extracellular protease activity by addition of serum albumin is not accompanied by Op1a transcription in cultures of WO-1 white cells or cultures of two additional clinical isolates of C . albicans, suggesting that expression of one or more other protease genes is stimulated in these cases . The results demonstrate that transcription of the Op1a gene is under the rigid control of switching in strain WO-1.

J Exp Med, 1992 Jul 1, 176(1), 19 - 25
Neutralizing antibody to interleukin 4 induces systemic protection and T helper type 1-associated immunity in murine candidiasis; Romani L et al.; An interleukin 4 (IL-4)-specific monoclonal antibody (mAb) was administered to mice infected systemically with the yeast Candida albicans, and the animals were monitored for mortality, development of delayed-type hypersensitivity, production of antibodies of different isotypes, release of IL-2, IL-4, IL-6, and interferon gamma (IFN-gamma) in vitro by splenic CD4+ lymphocytes, and levels of IL-4 and IFN-gamma mRNA in these cells . Neutralization of IL-4 by three weekly injections of mAb in several independent experiments resulted in an overall cure rate of 81% versus 0% of controls . Cure was associated with efficient clearance of the yeast from infected organs and histologic evidence of disease resolution, detection of strong T helper type 1 (Th1) responses, and establishment of long-lasting protective immunity . Soon after infection, and as a result of the first or second injection of mAb, there was a decrease in IL-4 mRNA in CD4+ cells, which was accompanied by an increase in the levels of IFN-gamma-specific transcripts . Our data thus indicate that the production of IL-4 by Th2 cells may limit Th1-associated protective immunity in murine candidiasis.

J Invest Dermatol, 1992 Jul, 99(1), 59 - 64
Effect of local ultraviolet irradiation on infections of mice with Candida albicans, Mycobacterium bovis BCG, and Schistosoma mansoni; Jeevan A et al.; In this study, we investigated whether mice given ultraviolet (UV)-B (280-320 nm) radiation in doses sufficient to alter cutaneous immune cells and impair the induction of contact hypersensitivity would also have impaired resistance to infectious agents administered at the site of UV irradiation . C3H mice were exposed to 400 J/m2 UVR from FS40 sunlamps on four consecutive days . Immediately after the last UV treatment, groups of mice were injected subcutaneously with Candida albicans, injected intradermally (ID) with Mycobacterium bovis bacillus Calmette-Guerin (BCG), or infected percutaneously with Schistosoma mansoni in UV-irradiated skin . The induction of the delayed hypersensitivity response to C . albicans and BCG, as assessed by footpad swelling, was unaffected by UV irradiation . However, the number of viable mycobacteria recovered from the lymphoid organs of BCG-infected mice was increased significantly in the UV-irradiated animals for a period of more than 2 months . Low-dose UV irradiation of the skin at the site of infection did not influence the number of S . mansoni parasites recoverable from the internal organs of mice that had been infected with cercariae percutaneously 6 weeks earlier . We conclude that the ability of UV radiation to impair the development of cell-mediated immunity to antigens introduced in a UV-irradiated site is not universal and depends on the particular antigen administered . We hypothesize that the involvement of epidermal Langerhans cells as the primary antigen-presenting cells in the induction of cell-mediated immunity may be the critical factor in determining whether a particular immune response will be affected by local UV irradiation.

Anal Biochem, 1992 Jul, 204(1), 96 - 102
Application of a fluorogenic substrate in the assay of proteolytic activity and in the discovery of a potent inhibitor of Candida albicans aspartic proteinase; Capobianco JO et al.; A fluorescent method for monitoring the activity of the secreted Candida carboxyl (aspartic) proteinase (EC 3.4.23.6) was developed using a fluorogenic substrate based on resonance energy transfer . The fluorescent assay was used to monitor proteinase production, purification, and inhibition . The Km for the fluorogenic substrate, 4-(4-dimethylaminophenylazo)benzoyl-gamma-aminobutyryl-Ile-His-Pro - Phe-His-Leu-Val-Ile-His-Thr- {5-(2-aminoethyl)amino}naphthalene-1-sulfonic acid, was found to be 4.3 microM at the optimum pH of 4.5 . Reaction products were separated by reverse-phase high-performance liquid chromatography and identified by amino acid analysis or by 252Cf plasma desorption mass spectrometry . Cleavage of the fluorogenic substrate was between the histidine-threonine residues, releasing the fluorescent product, threonine-{5-(2-aminoethyl)amino}naphthalene-1-sulfonic acid . Proteolytic activity was expressed as nanomoles of fluorescent product released at 22 degrees C/60 min, pH 4.5, and the release of 0.9 nmol product was equivalent to one hemoglobin proteolytic unit (O.D.A700 increase of 0.100) produced at 37 degrees C/60 min, pH 3.5 . The aspartic proteinase inhibitor pepstatin had an IC50 of 27 nM when tested in a dose-response study with the purified enzyme . The apparent Ki for pepstatis was 2.9 nM . Several synthetic inhibitors of the enzymes were identified with IC50's in the nanomolar range . The most potent compound, A70450, was characterized as a fast, tight-binding inhibitor having an IC50 of 1.3 nM and apparent Ki of 0.17 nM.

Cell Mol Biol, 1992 Jul, 38(4), 407 - 12
The effect of a mannose binding protein on macrophage interactions with Candida albicans; Kitz DJ et al.; A soluble mannose binding protein (MBP), obtained from rabbit serum, was found to inhibit phagocytosis of Candida albicans by bone marrow derived, cultured murine macrophages . During in vitro incubation of yeast with lymphocyte-free macrophage populations uptake of the yeast was significantly reduced at MBP concentrations of 5 micrograms/ml . A similar reduction in yeast phagocytosis was produced by dextrose, d-fucose, l-fucose, d-mannose and alpha-methyl-d-mannoside but required saccharide concentrations of 25-50 mg/ml . Inhibition of phagocytosis of the yeast also resulted from pretreatment of either the macrophages or the yeasts with MBP followed by washing . As expected, the addition of mannan to the assay medium blocked the inhibitory effect of MBP for uptake of C . albicans . These findings suggest that both cell bound and soluble mannose receptors may be important modulators of macrophage-Candida interactions.

An Esp Pediatr, 1992 Jul, 37(1), 63 - 5
{Intracardiac mycetoma induced by central catheterization}; Gonzalez Dieguez CC et al.; We report a case of an infective endocarditis presented as a right atrial mass which pathological study showed a big vegetation of candida albicans (mycetoma) . We think its presence was related to a great central vein catheterization during the neonatal period . The clinical feature was completed with pulmonary fungal embolism and later tricuspid valve afectation . With this work we wish to remark the necessary careful management of patients with central vein catheters to avoid this severe complication . We review the pharmacological and surgical treatment of this uncommon entity.

Agents Actions, 1992 Jul, 36(3-4), 207 - 11
Inhibition of histamine release from human granulocytes by ions of the rare earth elements lanthanum and cerium; Gruner S et al.; The influence of the ATPase inhibitors, lanthanum or cerium, on histamine release in basophils and mast cells was studied . Both compounds inhibited IgE- or A23187-induced histamine release . To exclude a general inhibition of calcium-dependent reactions in the cell, we tested the influence of these compounds on phagocytosis and superoxide production of neutrophil granulocytes . Phagocytosis of Candida albicans was inhibited partially, superoxide generation, measured by the INT test after stimulation with zymosan or aggregated gamma globulin, was not affected . Because of the inhibitory effect of lanthanum or cerium compounds on membrane ATPase and immunological function of epidermal Langerhans cells we propose that these compounds may be used in the treatment of atopic eczema, where both histamine-releasing mast cells and IgE-bearing Langerhans cell play a pathogenetically important role.

Indian J Pathol Microbiol, 1992 Jul, 35(3), 237 - 40
Incidence of mycoses in bronchopulmonary disorders; Kumar S et al.; A total of 274 samples were collected--180 sputum samples, 82 bronchial secretions and 12 pleural aspirates . Main fungus was Candida albicans from sputum (45.5 percent), from bronchial secretions (14.6 percent) . Rest were Aspergillus, Alternaria and Helminthosporium . All the pleural aspirates were negative for fungus.

Rev Soc Bras Med Trop, 1992 Jul-Sep, 25(3), 165 - 9
{Candidiasis in AIDS patients}; Campos CE et al.; A total of 35 in patients admitted at Emilio Ribas Hospital--Sao Paulo, Brazil, with digestive candidiasis and AIDS clinical diagnostic were evaluated 10 month later, being 29 male and 6 female; white outnumbering black with age ranged from 30 to 50 years old . Agar Sabouraud culture and tube germinative tests identified 28 (80%) Candida albicans out 35 strains . Minimum inhibitory concentration (MIC) 50% was against azoles (ketoconazole = 2.2 micrograms/ml; itraconazole = 21.0 micrograms/ml and fluconazole = 19.0 micrograms/ml); polyenes (nystatin = 50.0 micrograms/ml and amphotericin B = 0.12 micrograms/ml) and 5 fluorocytosine = 1.6 micrograms/ml . Siegel tests showed significant Candida albicans proportions in strains isolated from 35 AIDS patients . There was no significant relation between AMB doses and early or late death . Conclusions: candidiasis in AIDS patients showed high MIC 50% to azoles and nystatin and significant Candida albicans proportion in all strains isolated from AIDS patients . Previous amphotericin B therapy had no influence in early or late death in 30 patients . Previous therapy possibly explained MIC 50% increases in Candida strains.

Mycoses, 1992 Jul-Aug, 35(7-8), 177 - 80
Vaginal yeast colonization and promiscuity . A study of 197 prostitutes; Ginter G et al.; In order to study the role of promiscuity in yeast colonization of the vagina we examined vaginal smears of 197 prostitutes . Forty-two (21%) showed yeast infection on culture, and Candida albicans was isolated in 93% of these cases . This rate is comparable to the rates in reports of large series of non-promiscuous women in the literature and does not suggest that promiscuity alone is a predisposing factor for vaginal yeast carriage . The rate of Candida infections was approximately the same in prostitutes taking oral contraceptives as in those not taking the pill (22 and 21%, respectively; P > 0.05) . The prevalence of vaginal yeast colonization, however, was significantly higher in prostitutes under the age of 31 (30%) as compared with those over 30 (10%; P < 0.002), thus suggesting that women in the third decade of life are more prone to vaginal Candida infections than older age groups.

Mycoses, 1992 Jul-Aug, 35(7-8), 173 - 6
Quantitative assessment of the efficacy of oral ketoconazole for oral candidosis in HIV-infected patients; Korting HC et al.; Fifteen male patients with manifest oral candidosis due to Candida albicans, suffering from AIDS-related complex (ARC) or full-blown AIDS, were investigated both clinically and microbiologically before and about 1 and 4 weeks after 7 to 10 days of treatment with 200 mg ketoconazole p.o . per day . Candida albicans was quantitated in mouthwash fluid . The antimicrobial susceptibility of the Candida albicans isolates was assessed using the IC30 test . In the short term, clinical cure was obtained in 87%, mycological cure in 53% . In the long term, the corresponding figures were 56 and 9%, respectively . Eradication of Candida albicans was not possible if IC30 values exceeded 256 micrograms ml-1 . While pretreatment counts of Candida albicans in those patients also taking zidovudine did not differ from those in the rest of the study population, both the clinical and the mycological efficacy of ketoconazole seem to be higher both in the short and the long term when administered together with zidovudine . In consideration of the high relapse rate after about 4 weeks, an interval treatment protocol with oral ketoconazole is proposed.

Biochim Biophys Acta, 1992 Jun 30, 1107(2), 271 - 82
Amphotericin B-phospholipid interactions responsible for reduced mammalian cell toxicity; Perkins WR et al.; When interacting with phospholipid in an aqueous environment, amphotericin B forms unusual structures of markedly reduced toxicity (Janoff et al . (1988) Proc . Natl . Acad . Sci . USA 85, 6122-6126) . These structures, which appear ribbon-like by freeze-fracture electron microscopy (EM), are found exclusively at amphotericin B to lipid mole ratios of 1:3 to 1:1 . At lower mole ratios they occur in combination with liposomes . Circular dichroism (CD) spectra revealed two distinct modes of lipid-amphotericin B interaction, one for liposomes and one for the ribbon-like structures . In isolated liposomes, amphotericin B which comprised 3-4 mole percent of the bulk lipid was monomeric and exhibited a hemolytic activity comparable to amphotericin B suspended in deoxycholate . Above 3-4 mole percent amphotericin B, ribbon-like structures emerged and CD spectra indicated drug-lipid complexation . Minimal inhibitory concentrations for Candida albicans of liposomal and complexed amphotericin B were comparable and could be attributed to amphotericin a release as a result of lipid breakdown within the ribbon-like material by a heat labile extracellular yeast product (lipase) . Negative stain EM of the ribbon-like structures indicated that the ribbon-like appearance seen by freeze-fracture EM arises as a consequence of the cross-fracturing of what are aggregated, collapsed single lamellar, presumably interdigitated, membranes . Studies examining complexation of amphotericin B with either DMPC or DMPG demonstrated that headgroup interactions played little role in the formation of the ribbon-like structures . With these results we propose that ribbon-like structures result from phase separation of amphotericin B-phospholipid complexes within the phospholipid matrix such that amphotericin B release, and thus acute toxicity, is curtailed . Formation of amphotericin B-lipid structures such as those described here indicates a possible new role for lipid as a stabilizing matrix for drug delivery of lipophilic substances, specifically where a highly ordered packing arrangement between lipid and compound can be achieved.

Biochemistry, 1992 Jun 23, 31(24), 5680 - 6
Sequential nuclear magnetic resonance assignment of beta-1,2-linked mannooligosaccharides isolated from the phosphomannan of the pathogenic yeast Candida albicans NIH B-792 strain; Shibata N et al.; The H-1 and H-2 signals of beta-1,2-linked mannooligosaccharides isolated from the phosphomannan of Candida albicans NIH B-792 strain by mild acid hydrolysis were assigned by a sequential NMR assignment method that combines two-dimensional 1H-1H correlated spectroscopy (COSY) and two-dimensional nuclear Overhauser enhancement and exchange spectroscopy (NOESY) . The results indicated that the H-1 and H-2 of each beta-1,2-linked mannopyranose unit show largely different signals compared with those of the alpha-linked ones and that the correlation between linkages and signals could not be explained by a conventional additivity rule . Furthermore, a regular proportional downfield shift of the H-1 signal was observed in the order of the mannose unit from the reducing terminal except those of the reducing and nonreducing terminal positions . Although the 1H NMR spectra of these oligosaccharides were complicated due to the presence of a large portion of the beta-anomer from the reducing terminal mannose unit, reduction of the oligosaccharides with NaBH4 to the corresponding alcohols gave simple and more readily interpretable 1H NMR spectra . Unexpectedly, however, a shift of H-1 signals by this reduction occurred not only on the second mannose unit but also on the third and fourth mannose units from the modified reducing terminal group of each oligosaccharide alcohol . This result indicates that the reducing terminal mannose unit is able to affect up to the fourth mannose unit from the reducing terminal . The presence of a long-distance interresidue NOE also suggests that the beta-1,2-linked mannooligosaccharides have a compactly folded conformation in solution.

Nippon Kyobu Geka Gakkai Zasshi, 1992 Jun, 40(6), 1016 - 20
{Surgical treatment of Candida endocarditis involving mitral valve--a case report}; Ide H et al.; A 53-year-old male with a low pulmonary function (FEV1.0 500 ml) and cachexia was admitted for a remittent fever . Blood culture along with echocardiography indicating vegetation on the anterior mitral leaflet confirmed Candida endocarditis involving mitral valve . Following anti-fungal drug therapy, mitral valve replacement was performed . Surgical specimen of mitral valve showed vegetation on the anterior mitral leaflet with Candida albicans . The post-operative course was uneventful, through the anti-fungal drug therapy was compelled to be discontinued owing to drug allergy . He was discharged on the 67th postoperative day . There was no evidence of recurrence without medication for 9 months after his discharge.

J Med Microbiol, 1992 Jun, 36(6), 428 - 36
Virulence and adhesive properties of serotypes A and B of Candida albicans isolated from paediatric burn patients; Kennedy MJ et al.; The virulence and adhesive properties of 50 isolates of Candida albicans serotypes A and B collected over 6 years from 48 paediatric burn patients were examined to provide more detailed information about candidal pathogenesis in burn patients and to examine the relevance of the commonly used epithelial cell adhesion assay for determining fungal virulence . The isolates represented a fair distribution of serotypes (29 isolates were serotype A and 21 isolates were serotype B) and a total of 28 serotype-biotype combinations were found; 32% of the serotype-biotype combinations appeared only once, while 44% of the isolates showed similar biotype tests for two of three digits . Adhesion of the isolates to plastic and to buccal epithelial cells (BECs) was examined and compared after growth in a chemically defined medium . There were significant differences in the adhesion of individual isolates to plastic or BECs, but no correlation was found between biotype and adhesiveness . Serotype B isolates were found to be more adhesive to BECs (p less than 0.05) but not to plastic . There was no apparent correlation between candidal adhesiveness and site of isolation from these patients (autografts, blood, faeces, throat swabs, tracheal aspirates, wounds and intravenous catheters), although isolates from catheters were generally less adhesive to epithelial cells . Virulence in a systemic infection mouse model revealed that there were significant differences in virulence between isolates, but no correlation was found between virulence and the biotype, serotype or site of isolation . Similarly, no correlation was found between virulence and adhesiveness or cell-surface hydrophobicity.(ABSTRACT TRUNCATED AT 250 WORDS)

J Dent Res, 1992 Jun, 71(6), 1298 - 303
Chlorhexidine effects on membrane lipid domains of human buccal epithelial cells; Audus KL et al.; The effect of chlorhexidine gluconate on the adherence of Candida albicans to human buccal epithelial cells (BEC) and drug-induced alterations in BEC membrane-lipid packing order were examined . Treatment of BEC with attached yeasts with 0.1 and 0.2% chlorhexidine resulted in significant yeast detachment after 90 and 60 min, respectively . Following pre-treatment of BEC with greater than 0.1% chlorhexidine, yeast adherence was inhibited by greater than 80% . In parallel experiments, the fluorescence anisotropy of BEC labeled with fluorescent membrane probes--diphenylhexatriene (DPH) and trimethylammonium DPH--was assessed following exposure to chlorhexidine . The fluorescence anisotropy decreased with increasing concentrations of chlorhexidine, which indicated that the drug decreased epithelial-cell membrane-lipid packing order . Chlorhexidine concentrations that altered epithelial-cell membrane-lipid packing order, particularly in superficial regions, were similar to those drug concentrations required for detachment of adherent yeasts . Similar results were obtained with a second antifungal, nystatin A . While the effects of chlorhexidine on the buccal-cell membrane-lipid packing order were not reversed by multiple washings, the opposite situation occurred with nystatin A . The results suggest that chlorhexidine-induced alterations of BEC membrane-lipid order may be involved in the antifungal actions of the drug.

Surgery, 1992 Jun, 111(6), 647 - 55
Effects of laparotomy on systemic macrophage function; Redmond HP et al.; Surgical trauma induces immunosuppression that may adversely influence survival . This study examined the effect of laparotomy on two different macrophage populations, peritoneal macrophages (PM phi) and Kupffer cells . Female, 6- to 8-week old, CFW/C3H-HeN mice (n = 160) were randomly allocated to one of three study groups: control, ether anesthetic only, or ether anesthetic and laparotomy . On postoperative days 1 and 3, PM phis and Kupffer cells were harvested and assayed for superoxide anion production (O2-), percent macrophage phagocytosis of Candida albicans (CAP), percent C . albicans killed by macrophages (CAK), percent major histocompatibility complex (MHC)-class II antigen expression, and antigen presentation . Macrophages isolated on postoperative day 1 were also cocultured with 100 units/10(6) cells/ml interferon-gamma (IFN-gamma) . Laparotomy significantly impaired microbicidal activity (O2-, percent CAP, and percent CAK) and antigen presentation on postoperative day 1 . On postoperative day 3, O2- and antigen presentation were increased significantly (p less than 0.05) over control values, indicating a rebound phenomenon . Kupffer cell microbicidal function was unchanged on postoperative days 1 and 3 . The initial immune impairment (PM phis: O2-, CAP, and CAK) was abrogated by IFN-gamma treatment . In immunosuppressed hosts after injury, administration of macrophage-activating factors such as IFN-gamma could be of therapeutic benefit.

J Exp Med, 1992 Jun 1, 175(6), 1643 - 51
A role for complement receptor-like molecules in iron acquisition by Candida albicans; Moors MA et al.; Candida albicans, an opportunistic fungal pathogen of humans, is dependent upon iron for growth . Consequently, human serum inhibits C . albicans growth due to the presence of high affinity iron-binding proteins that sequester serum iron, making it unavailable for use by the organism . We report that in the inhibitory environment of human serum, the growth of C . albicans can be restored by the addition of exogenous hemoglobin or heme, but not by protoporphyrin IX, the heme precursor that does not contain iron . We further report that C . albicans can utilize cell surface proteins that are homologues of the mammalian complement receptors (CR) to rosette complement-coated red blood cells (RBC) and obtain RBC-derived iron for growth . The ability of Candida to acquire RBC-derived iron under these conditions is dependent upon Candida-RBC rosetting mediated by CR-like molecules . Unopsonized RBC do not support Candida growth in serum, and restoration of Candida growth in serum by complement-opsonized RBC is inhibited by monoclonal antibodies to the human CR type 3 (CR3) . In addition, activation of the human alternative pathway of complement by Candida leads to "bystander" deposition of C3 fragments on the surface of autologous, unopsonized RBC, generating the ligands necessary for Candida-RBC rosetting . These results suggest that C . albicans has evolved a unique strategy for acquiring iron from the host, which exploits the host complement system, and which may contribute to the pathogenic potential of the organism.

Cell Immunol, 1992 Jun, 142(1), 137 - 44
Candida albicans hyphal form enhances tumor necrosis factor mRNA levels and protein secretion in murine ANA-1 macrophages; Blasi E et al.; We have demonstrated that Candida albicans in its hyphal form (H-Candida) acts as a stimulating agent in the cloned macrophage population ANA-1 . Both tumor necrosis factor (TNF) mRNA levels and secreted biological activity augment in ANA-1 macrophages exposed to H-Candida . Such effects are observed at an effector-to-target cell ratio of 1:1 and occur after 1 and 3 hr of coincubation, respectively . The phenomenon is independent of the metabolic status of the fungus, since viable as well as heat-killed H-Candida are comparable in inducing TNF mRNA levels . The extent and kinetics of H-Candida-mediated effects are similar to those observed following exposure of ANA-1 macrophages to lipopolysaccharide (LPS) . This implies that C . albicans in its hyphal form is a potent macrophage modulator; whether it acts through the same mechanism(s) as LPS remains to be elucidated.

Mycopathologia, 1992 Jun, 118(3), 179 - 83
Susceptibility of clinical isolates of fungi to saperconazole; Otcenasek M; The in vitro activity of saperconazole against 228 strains of mycotic agents belonging to 48 species was investigated . Susceptibility testing was performed using a microtiter broth dilution method . Isolates of Candida albicans, C . tropicalis and Torulopsis glabrata showed distinct intra-species variation of susceptibility with MIC values ranging from 0.045 to 100 mg l-1 . The drug was inhibitory for the dermatophytes at a relatively narrow range of concentrations, most isolates being inhibited at MIC 0.78 mg l-1 . The strongest antifungal potency of saperconazole was exerted against clinical isolates of the genus Aspergillus (MIC 90% = 0.19 mg l-1) . Concentrations up to 100 mg l-1 had no macroscopically recognizable effect on the growth of zygomycetous fungi (Mucor, Rhizopus, Syncephalastrum) . Species of the genus Absidia with their good sensitivity are an exception . Justification of in vitro susceptibility testing of triazoles is discussed . In the author's opinion, MIC values can serve as an informative parameter showing the range of indications of these antifungals for treatment . It is concluded that saperconazole exhibits a very good activity against a broad spectrum of medically important fungi in vitro and can be considered a promising antifungal drug.

Mycopathologia, 1992 Jun, 118(3), 127 - 31
Immunodiffusion test for diagnosing basidiobolomycosis; Imwidthaya P et al.; An immunodiffusion test was developed for the diagnosis of basidiobolomycosis . When culture filtrate antigen (CFA) from Basidiobolus ranarum was reacted against two human patient and two rabbit antisera, 2 precipitin bands, inner (N) and outer (Y), were revealed for both patient and rabbit antisera . A line of identity was also observed between precipitin bands obtained with patient and rabbit sera . When CFA from B . ranarum (B CFA) was reacted against rabbit sera which contained antibody to Conidiobolus coronatus and Pythium insidiosum, 1 precipitin band corresponding to inner band (N) was observed . This finding showed that B . ranarum, C . coronatus and P . insidiosum shared at least one common antigen . After B CFA was absorbed with Pythium rabbit antiserum, the inner precipitin line that occurred between B CFA and rabbit antisera of Pythium and Conidiobolus disappeared . However, with Basidiobolus rabbit antiserum, the result did not change . The antigens which could be demonstrated by inner (N) and outer (Y) precipitin bands were heat stable at 56 degrees C for 30 min . The titer of the antibodies specific to these antigens decreased as the lesions subsided . When B . ranarum CFA was reacted against sera from 20 apparently normal persons, 20 diabetes mellitus patients, 5 aspergillosis patients, 2 candidosis patients and 3 pythiosis patients, no precipitin band was found . B . ranarum CFA was also treated with each rabbit antiserum specific to Candida albicans, Malassezia furfur and Aspergillus fumigatus . No precipitin bands occurred with any of these antisera . Thus, this test was found to be practical, sensitive and specific, and can be used to monitor patients infected with Basidiobolus ranarum.

J Surg Res, 1992 Jun, 52(6), 537 - 42
Endotoxin promotes synergistic lethality during concurrent Escherichia coli and Candida albicans infection; Burd RS et al.; Previous studies have suggested that the lipopolysaccharide (LPS, endotoxin) component of the gram-negative bacterial cell wall is a key virulence factor that serves to enhance mortality during infections in which fungi and gram-negative bacteria are copathogens . To test this hypothesis, mice were challenged ip with Escherichia coli 0111:B4, Candida albicans, or both, and the effect of administration of anti-E . coli 0111:B4 LPS monoclonal antibody (mAb) 8G9 on endotoxemia, bacteremia, and mortality was assessed . E . coli (2 x 10(7) colony-forming units (CFU)) plus C . albicans (6 x 10(7) CFU) infection produced 100% mortality at 7 days, compared to the relatively low mortality caused by infection with either E . coli or C . albicans alone (20 and 3%, respectively, P less than 0.01) . Administration of mAb 8G9 to animals receiving both pathogens reduced mortality (100% versus 14%, P less than 0.05), endotoxemia (3653 +/- 3187 versus 2 +/- 2 endotoxin units (EU), P less than 0.01), and bacteremia (4.2 +/- 2.3 versus 1.1 +/- 2.1 log(CFU/ml), P less than 0.01) compared to animals receiving saline alone . In a separate series of experiments, purified E . coli 0111:B4 LPS was administered in place of viable E . coli . The simultaneous injection of 200 micrograms E . coli LPS and C . albicans (6 x 10(7) CFU) produced 93% mortality at 7 days, compared to the low mortality that occurred following injection with either E . coli 0111:B4 LPS or C . albicans alone (21 and 3% respectively, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

J Antibiot (Tokyo), 1992 Jun, 45(6), 854 - 60
Production and biological activities of a new antifungal antibiotic, TAN-950 A; Hakoda S et al.; A novel antifungal antibiotic, TAN-950 complex, was isolated from the culture filtrate of Streptomyces platensis A-136 (IFO 14603, FERM BP-1786) . The water-soluble amphoteric substances in this complex were purified by chromatography using ion-exchange resins, QAE-Sephadex and adsorptive resins and were designated TAN-950 A and TAN-950 A-E mixture . The molecular formula of TAN-950 A was determined to be C6H7N2O4Na for the sodium salt . This new amino acid antibiotic showed antifungal activity against Candida albicans in vitro and in vivo, and had low toxicity in mice.

Arzneimittelforschung, 1992 Jun, 42(6), 836 - 40
In vitro and in vivo studies with flutrimazole, a new imidazole derivative with antifungal activity; Garcia Rafanell J et al.; 1-{(2-Fluorophenyl)(4-fluorophenyl)phenylmethyl}-1H-imidazole (flutrimazole, UR-4056, CAS 119006-77-8) is a new topical imidazole antifungal agent which displays potent broad-spectrum in vitro activity against dermatophytes, filamentous fungi and yeasts, saprophytic and pathogenic to animals and humans (MIC = 0.025-5.0 micrograms/ml) . In most of these studies the activity of flutrimazole was comparable to that of clotrimazole and markedly higher than that of bifonazole (MIC differences of greater than or equal to 1 order of magnitude) . Tested against Scopulariopsis brevicaulis (8 strains), both flutrimazole and clotrimazole exhibited fungistatic and fungicidal activity, and clotrimazole appeared something less active (MIC = 0.3-2.5 micrograms/ml) than flutrimazole (MIC = 0.15-0.6 micrograms/ml) . In animal experiments, topical application of 1% and 2% flutrimazole, as a cream or solution, was highly effective in models of rat vaginal candidiasis and guinea-pig trichophytosis, giving a rate of cured or cured plus markedly improved animals higher than 80% . Flutrimazole shares the mode of action of other imidazole or triazole-containing antifungals, i.e . inhibition of fungal lanosterol 14 alpha-demethylase, as it strongly inhibits ergosterol biosynthesis in a cell-free homogenate of Candida albicans, with an IC50 value of 0.071 mumol/l.

Antimicrob Agents Chemother, 1992 Jun, 36(6), 1284 - 9
Positive interaction of nikkomycins and azoles against Candida albicans in vitro and in vivo; Hector RF et al.; Nikkomycins X and Z (NZ), competitive inhibitors of fungal chitin synthetase, were combined with azoles in a series of in vitro checkerboard assays to test for synergism against Candida spp . All combinations of nikkomycins and azoles tested resulted in marked synergistic activity against an isolate of Candida albicans, with fractional inhibitory concentration indices ranging from 0.016 to 0.28 . No synergistic effect was demonstrable with isolates of C . tropicalis, C . parapsilosis, or C . krusei, though results for the latter two were suggestive of an additive effect . In survival models of mice infected intravenously with C . albicans, NZ administered singly in doses ranging from 5 to 50 mg/kg of body weight twice a day was able to delay the onset of mortality but showed no dose-response effect . The combination of NZ and the azole R 3783 administered orally in a ratio of 8:1 to 40:1 or greater (wt/wt) enhanced survival better than did the drugs given individually, but this effect was less evident for combinations involving fluconazole . In short-term organ load assays with outbred mice infected intravenously with C . albicans, high ratios of NZ to R 3783 reduced the CFU per gram in kidneys more significantly than did the drugs individually . Statistically significant reductions were not seen for short-term fungal burden assays using combinations of NZ and fluconazole in outbred mice or in inbred mice more susceptible to candidiasis . In a model of rat vaginal candidiasis, the combination of NZ and R 3783 administered either orally or vaginally was more effective than the drugs used singly . Thus, under certain conditions, combination therapy with nikkomycin and select azoles may offer promise for an increased therapeutic effect in candidiasis.

Antimicrob Agents Chemother, 1992 Jun, 36(6), 1225 - 9
Combined effect of fluconazole and recombinant human interleukin-1 on systemic candidiasis in neutropenic mice; Kullberg BJ et al.; The aim of the present study was to investigate the efficacy of treatment with a combination of fluconazole and human recombinant interleukin-1 alpha (IL-1 alpha) in normal or neutropenic mice with systemic Candida albicans infection . Six hours after intravenous injection of 5 x 10(4) CFU of C . albicans organisms, oral treatment twice daily with 2.5 or 10 mg of fluconazole per kg of body weight, a single intraperitoneal injection of 80 ng of IL-1, or a combination of the two was started . IL-1 had no influence on the antifungal activity of fluconazole in vitro or on the pharmacokinetics of fluconazole . For both normal and neutropenic mice, the number of C . albicans organisms cultured from the kidneys after 36 h of treatment was significantly lower in mice treated with IL-1 alone than in untreated animals . Treatment with fluconazole alone also significantly lowered the number of C . albicans organisms in the kidneys compared with that in untreated controls . In normal mice, the combination of fluconazole and IL-1 was not better than fluconazole alone . In neutropenic mice, combined treatment with IL-1 and 10 mg of fluconazole per kg led to significantly lower numbers of C . albicans organisms in the kidneys and the spleen than treatment with either agent alone . Although the precise mechanism by which IL-1 enhances resistance to infection is not clear, the additive effect of IL-1 and fluconazole in vivo indicates that combined therapy with immunomodulators and antifungal drugs is beneficial in immunocompromised mice with systemic fungal infections.

Intern Med, 1992 Jun, 31(6), 766 - 9
Humoral and cellular immunity to Candida albicans in patients with bronchial asthma; Tanizaki Y et al.; Delayed cutaneous reactivity to Candida albicans (C . albicans) and PPD (purified protein derivative) was examined in 52 patients with bronchial asthma in relation to the production of specific IgG4 antibodies against the antigen . 1 . The frequency of a positive, immediate skin reaction to C . albicans was similar among the five age groups, ranging from 60.0% to 66.7% . 2 . The incidence of a positive delayed skin reaction to C . albicans was lower in patients between the ages of 10 and 30 and tended to decrease with aging in the patients over the age of 51 . 3 . A delayed skin reaction to PPD was positive in patients between 31 and 50 with a higher incidence; this incidence decreased in patients over age 51 . 4 . The level of C . albicans-specific IgG4 antibodies was significantly higher (26.7 u/ml) in patients with a negative delayed skin reaction to the antigen than in those with a positive reaction (5.9 u/ml) (p less than 0.001) . There was no correlation between delayed skin reaction to PPD and production of specific IgG4 antibodies.

J Pak Med Assoc, 1992 Jun, 42(6), 140 - 3
Candida onychomycosis--an evaluation of the candida species as primary keratinolytic yeasts in nail disease; Qamar AG; This is a pilot study of 5 nail specimens to evaluate the role of candida species in onychomycosis by taking pure isolates of different species of candida, growing these yeasts with normal nail keratin and assessing the growth of fungus periodically macroscopically and the final evaluation was made under electron microscope . The results suggest that the candida albicans primarily has an important role in keratolysis of nails.

J Med Microbiol, 1992 Jun, 36(6), 367 - 70
The 14th C . L . Oakley Lecture . Candida albicans HSP 90: link between protective and auto immunity; Matthews RC; Heat shock proteins (HSP) are thought to play a role in the aetiology of autoimmune diseases, but are also common targets for the immune response to many infections . Patients recovering from systemic candidosis produce antibodies to Candida albicans HSP 90, both to species-specific epitopes and, more commonly, to epitopes shared with human HSP 90 . One such autoreactive antibody was protective in a mouse model of systemic candidosis.

Infect Immun, 1992 Jun, 60(6), 2493 - 9
Role of specific determinants in mannan of Candida albicans serotype A in adherence to human buccal epithelial cells; Miyakawa Y et al.; Candida albicans serotype A (C . albicans A) possesses a specific antigen, designated antigen 6, which resides in mannans on the cell surface . To determine the role of the mannan moiety of the C . albicans cell wall in adherence to buccal epithelial cells, we used antigen 6-deficient mutants which had been isolated by screening with an agglutinating monoclonal antibody against antigen 6 (MAb-6) . 1H nuclear magnetic resonance spectral analysis of the purified mannans from the mutants showed a loss of the signals related to that beta-linkage of the side chains . Moreover, acetolyzed fragments of the mutant mannans showed a decreased amount of mannohexaose and mannopentaose . The mutant yeast cells exhibited significantly reduced ability to adhere both to exfoliated buccal epithelial cells and to a human buccal cell line . A number of strains of C . albicans A, C . tropicalis, and C . glabrata, all of which bear antigen 6, showed significantly higher adherence to the cell line than did those of C . albicans serotype B, which lack antigen 6 . The whole mannan from the C . albicans A parent inhibited the adherence of C . albicans A to epithelial cells dose dependently, whereas mannan from a mutant strains did not . Moreover, C . albicans A treated with MAb-6 or polyclonal factor 6 serum showed reduced adherence . A close correlation was found between adhesive ability and agglutinability with MAb-6 in the C . albicans A parent, the antigenic mutants, and their spontaneous revertants . These results suggest that so far as mannan adhesion is concerned, serotype A-specific determinants are largely involved in the mechanisms of adherence of C . albicans A to human buccal epithelial cells.

J Gen Microbiol, 1992 Jun, 138 ( Pt 6), 1177 - 84
Clonal variation of chromosome size derived from the rDNA cluster region in Candida albicans; Iwaguchi S et al.; Of the eight Candida albicans chromosomes, chromosome 2, assigned by the MGL1 probe, is more variable in size than the other chromosomes among strains . We found that the clonal variation of chromosome 2, which carries a rDNA gene, occurred at a frequency of up to 10% of the progeny clones . After total chromosomal digestion with XhoI, which has no recognition sites within the rDNA repeat unit, the fragments containing the rDNA cluster were detected by Southern hybridization . The difference in fragment sizes corresponded to the clonal size variation of chromosome 2 . The intensity of hybridization with rDNA also correlated with the difference in size . In addition, there was no size change in the non-rDNA region as detected by NotI digestion of chromosome 2, and there was no observed change in the individual rDNA basic repeat unit size . From these lines of evidence, we confirmed that the clonal size variation of chromosome 2 which occurs at high frequency is derived from the size change of the rDNA cluster.

Leuk Res, 1992 Jun-Jul, 16(6-7), 703 - 9
Effects of human interleukin 3, macrophage and granulocyte-macrophage colony-stimulating factor on monocyte function following autologous bone marrow transplantation; Fabian I et al.; The effects of human interleukin 3 (IL-3), macrophage colony-stimulating factor (M-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were studied on the functional activity of human peripheral blood monocytes from healthy individuals and from eight patients at 4, 8 and 12 weeks following autologous bone marrow transplantation (ABMT) . Functions studied included superoxide production, phagocytosis of Candida albicans and reduction of 3-{4,5-dimethylthiazol-2-yl}-2.5-diphenyl tetrazolium bromide (MTT) . IL-3 and GM-CSF significantly enhanced the oxidative metabolism of monocytes from healthy individuals, while the effect of M-CSF was moderate . A considerable variability between healthy individuals was found in both resting and cytokine-stimulated monocytes with regard to superoxide production . All three investigated CSFs, i.e . IL-3, M-CSF and GM-CSF did not affect phagocytosis of C . albicans by the cells or their metabolic activity (reduction of MTT) . In ABMT patients no deficit in the functional activity of monocytes was found at any time after transplantation and all three CSFs investigated did not modulate the functional activity of the cells . These results suggest that monocytes do not have a major role in infectious complications post-ABMT.

Biochem J, 1992 May 15, 284 ( Pt 1), 47 - 52
Mechanism of action of purpuromycin; Landini P et al.; Purpuromycin, an antibiotic active against both fungi and bacteria, shows different modes of action against these two kinds of micro-organisms; in Candida albicans it inhibits RNA synthesis, whereas in Bacillus subtilis protein synthesis is primarily affected, with DNA and RNA synthesis blocked at higher concentrations of the drug . In bacterial cell-free protein-synthesis systems, purpuromycin did not inhibit synthesis from endogenous mRNA (elongation of peptides initiated within the intact cell) but inhibited MS2-phase RNA-dependent protein synthesis (which requires initiation) by 50% at 0.1 mg/l . Poly(U)-directed polyphenylalanine synthesis was 50% inhibited by 20 mg of purpuromycin/l when added to a complete system; however, when purpuromycin was preincubated with ribosomes dissociated into 30 S and 50 S subunits, the concentration for 50% inhibition fell to 0.1 mg/l . By contrast, in a C . albicans cell-free system poly(U)-directed polyphenylalanine synthesis was partially inhibited only at 200 mg/l . Purpuromycin also inhibited polynucleotide synthesis in vitro in reactions using Escherichia coli or wheat-germ RNA polymerases or E . coli DNA polymerase I . We suggest that in bacteria the primary target of purpuromycin is on ribosomes and that its action precedes the elongation step of protein synthesis . The effect on nucleic acid synthesis in both fungi and bacteria may be due to interaction of purpuromycin with DNA.

J Photochem Photobiol B, 1992 May 15, 13(3-4), 275 - 88
In vitro phototoxicity of nifedipine: sequential induction of toxic and non-toxic photoproducts with UVA radiation; Gibbs NK et al.; Anecdotal reports suggest that the dihydropyridine calcium antagonist, nifedipine (NIF), may be phototoxic in human skin . We have studied NIF phototoxicity in vitro using UVA fluorescent tubes (Sylvania PUVA) . NIF was phototoxic to Candida albicans and induced photohaemolysis both with NIF present during irradiation and with pre-irradiated drug . In V79 hamster fibroblasts, NIF (10 micrograms ml-1) was phototoxic MTT assay) 24 h after irradiation (0-112 kJ m-2); at 7.5 kJ m-2, about 70% of cells were damaged whilst at 37.5 kJ m-2, only about 45% of cells were damaged . A similar pattern was seen with pre-irradiated NIF . Absorption spectroscopy showed that the NIF absorption maximum (Amax approximately 340 nm) blue-shifted to 314 nm at low UVA doses (7.5 kJ m-2 or less) and red-shifted to 345 nm at higher doses (isosbestic point, 325 nm) . Thin layer chromatography of irradiated NIF showed a single photoproduct (PP1; Amax approximately 314 nm) formed at 7.5 kJ m-2 or less which disappeared at higher UVA doses to give further photoproducts . PP1 was highly dark toxic to V79 cells (50% damage at about 5 micrograms ml-1) but PP1 pre-irradiated with UVA was non-toxic . Preliminary gas chromatography-mass spectroscopy studies suggest that PP1 is the nitroso derivative of NIF . These results indicate that NIF phototoxicity in vitro is partially mediated by initial formation of a toxic photoproduct (PP1) but, paradoxically, subsequent UVA irradiation may reduce phototoxicity . The NIF concentrations required to induce in vitro phototoxicity are much greater than therapeutic plasma levels . Unless there is skin accumulation of NIF or PP1, our in vitro results suggest that NIF may not be an important skin-photosensitizing agent in vivo.

J Mol Biol, 1992 May 5, 225(1), 217 - 8
Crystallization of the exo(1,3)-beta-glucanase from Candida albicans; Cutfield S et al.; An exoglucanase, with specificity for beta (1,3) linkages, from the cell wall of Candida albicans has been crystallized by the hanging drop method in the presence of polyethylene glycol 8000 . The crystals, which diffract to better than 1.9 A resolution, belong to the orthorhombic space group P212121 with cell constants a = 60.2 A, b = 65.2 A, c = 96.5 A and with one molecule in the asymmetric unit.

Infection, 1992 May-Jun, 20(3), 168 - 70
Comparison of the efficacy of cilofungin, fluconazole and amphotericin B in the treatment of systemic Candida albicans infection in the neutropenic mouse; Bannatyne RM et al.; The relative efficacies of cilofungin, amphotericin B and fluconazole were compared in the treatment of systemic Candida albicans infection in neutropenic mice . Thirty-one day survival rates were lowest for cilofungin (14.6%), intermediate for amphotericin B (37.6%) and highest for fluconazole (50.5%) . Residual tissue infection in surviving animals was observed with all agents, but was heaviest with fluconazole, especially in the kidneys.

Arzneimittelforschung, 1992 May, 42(5A), 757 - 60
Phase II study of the therapeutic efficacy and safety of the new antimycotic sertaconazole in the treatment of superficial mycoses caused by Candida albicans; Umbert P et al.; The activity of 7-chloro-3-{1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethoxy-methyl} benzo{b}thiophene (sertaconazole, FI-7045, CAS 99592-32-2) was studied in a randomized parallel double-blind clinical trial on 20 patients suffering from superficial mycosis caused by Candida albicans (confirmed microscopically and microbiologically) . The patients were divided into two groups; one received sertaconazole 1% cream (10 patients) and the other received sertaconazole 2% cream (10 patients), over a period of 28 days . Clinical, microscopic and microbiological parameters were evaluated . Analytical parameters such as the appearance of possible undesirable effects (both local and general) were also monitored . The cure was total for 19 out of the 20 patients, demonstrating high efficacy . There were no relapses of infection in any of the cured patients . No local or general effects were recorded during the trial . The analytical parameters remained within normal limits . The clinical and microbiological cure, absence of relapses and the non-existence of local and general undesirable effects indicate that sertaconazole may represent an important advance in the therapy of superficial mycosis caused by Candida albicans.

Arzneimittelforschung, 1992 May, 42(5A), 721 - 4
Direct membrane-damaging effect of sertaconazole on Candida albicans as a mechanism of its fungicidal activity; Agut J et al.; The direct action of 7-chloro-3-{1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethoxy- methyl}benzo{b}thiophene (sertaconazole, FI-7045, CAS 99592-32-2) on the membrane integrity of C . albicans is studied by quantifying the leakage of intracellular adenosine triphosphate (ATP) into the medium as an index of the changes in membrane permeability and integrity and cell viability of the culture used . Sertaconazole caused a dose-dependent decrease in intracellular ATP after only 10-min exposure and a concomitant significant increase in extracellular ATP . This behaviour is characteristic of antifungals which are fungicidal as a result of a direct membrane damage . Thus sertaconazole, in addition to the mechanism of action responsible for its fungistatic activity (inhibition of ergosterol synthesis), has a second mechanism of action providing a significant fungicidal activity due to direct cell membrane damage.

Arzneimittelforschung, 1992 May, 42(5A), 718 - 20
Inhibition of ergosterol synthesis by sertaconazole in Candida albicans; Agut J et al.; 7-Chloro-3-{1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl) ethoxy-methyl} benzo {b} thiophene (sertaconazole, FI-7045, CAS 99592-32-2), a new topical antifungal agent, has shown activity against a broad range of clinically relevant yeasts and fungi . In the present study, the molecular basis of the pharmacological action of sertaconazole was examined by investigating the inhibition of ergosterol synthesis in cultures of Candida albicans, ATCC E-10.231, at 6 x 10(5) cells/ml grown aerobically at 37 degrees C, using various concentrations of sertaconazole . Sertaconazole inhibited the ergosterol synthesis with IC50 = 115 nmol/l . The results show that one of the mechanisms of action of sertaconazole consists in the inhibition of ergosterol synthesis.

Arzneimittelforschung, 1992 May, 42(5A), 711 - 4
In vitro comparative study of the fungistatic and fungicidal activity of sertaconazole and other antifungals against Candida albicans; Palacin C et al.; The fungistatic and fungicidal activity of 7-chloro-3-{1-(2, 4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethoxy-methyl}benzo{b}thiophene (sertaconazole, FI-7045, CAS 99592-32-2) against Candida albicans was determined and compared with that obtained for other antifungals . The fungistatic activity of sertaconazole, evaluated through the MIC obtained in Sabouraud and YNB media, gave results comparable to those obtained with miconazole and clotrimazole, and superior to those presented by bifonazole and ketoconazole . The fungicidal activity, evaluated by means of the 90% reduction in viable cells, took place at a concentration of 8 micrograms/ml for sertaconazole and at higher concentrations for the other drugs studied.

Arzneimittelforschung, 1992 May, 42(5A), 705 - 10
In vitro antifungal activity of sertaconazole; Drouhet E et al.; The antifungal activity of 7-chloro-3-{1-(2,4-dichlorophenyl)-2-(1H- imidazol-1-yl)ethoxy-methyl}benzo{b}thiophene (sertaconazole, FI-7045, CAS 99592-32-2) versus miconazole has been studied in vitro against yeast-like fungi, dermatophytes and other filamentous fungi . Candida albicans was very sensitive to sertaconazole both in serotype A and serotype B strains (MIC = 0.21 micrograms/ml) . Sensitivity of Candida non albicans species (MIC = 0.17 microgram/ml), Torulopsis (MIC = 0.09 microgram/ml) and Trichosporon (MIC = 0.09 microgram/ml) was also remarkable . For dermatophytes, partial inhibitions were observed at concentrations of 0.04 and 0.09 microgram/ml, the 50% inhibition ranging between 0.36 and 12.56 micrograms/ml for most strains . Filamentous opportunistic fungi were less sensitive to azoles, although sertaconazole MICs were lower than those of miconazole . Sertaconazole also proved to possess a remarkable fungicidal activity on all strains of Candida albicans under study.

Yeast, 1992 May, 8(5), 337 - 52
Isolation and sequence analysis of the gene encoding translation elongation factor 3 from Candida albicans; Di Domenico BJ et al.; The structural gene encoding translation elongation factor 3 (EF-3) has been cloned from a Candida albicans genomic library by hybridization to a Saccharomyces cerevisiae probe containing the Saccharomyces gene, YEF3 (Sandbaken et al., 1990b) . The sequences were shown to be functionally homologous to the Saccharomyces gene by three criteria: (1) a Saccharomyces strain transformed with a high copy plasmid containing CaEF3 sequences overproduces the EF-3 peptide two-fold; (2) extracts from this strain exhibit a two-fold increase in the EF-3-catalysed, ribosome-dependent ATPase activity (Kamath and Chakraburtty, 1988); and (3) the Candida gene complements a Saccharomyces null mutant . The coding region, identified by DNA sequencing, indicates that CaEF3 encodes a 1050 amino acid polypeptide having a potential molecular weight of 116,865 Da . This protein shows 77% overall identity to the Saccharomyces YEF3 gene, with a significantly greater identity (94%) concentrated in the region of the protein thought to contain the catalytic domain of EF-3 (Sandbaken et al., 1990a) . The upstream non-coding region contains T-rich regions typical of many yeast genes and several potential RAP1/GRF1 elements shown to regulate expression of a number of translational genes (Mager, 1988) . The data confirm a high degree of conservation for EF-3 among the two organisms.

J Antibiot (Tokyo), 1992 May, 45(5), 639 - 47
The squalestatins, novel inhibitors of squalene synthase produced by a species of Phoma . I . Taxonomy, fermentation, isolation, physico-chemical properties and biological activity; Dawson MJ et al.; During the screening of fungi for inhibitors of squalene synthase, Phoma sp . C2932 was found to produce three structurally related novel inhibitors . These compounds, designated the squalestatins, exhibited potent activity against both mammalian (rat liver) and fungal (Candida albicans) squalene synthase . Furthermore, they also had broad spectrum in vitro antifungal activity.

Int J STD AIDS, 1992 May-Jun, 3(3), 157 - 60
Candida infections in AIDS patients; Odds FC; PIP: In 1987, data from the Centers for Disease Control AIDS data base indicated a 50% prevalence of oropharyngeal Candida infection, a 10% rate of esophageal infection, and .5% rate of bronchopulmonary infection among AIDS patients . Candida-positive blood cultures were found in 13 of 903 AIDS patients, and disseminated Candida infection was ascertained in 11 of 101 post mortem examinations of AIDS victims . 5 of 12 patients with oral Candida infection progressed to AIDS within a 42-week investigation as opposed to only 1 of 17 patients without Candida . In the former group, CD4 counts and CD4/CD8 ratios were also significantly lower . Most infections were caused by Candida albicans . Genital Candida occurs in 5-20% of women in reproductive age . In a study of 66 HIV-infected women Candida vaginitis preceded oral Candida infections which preceded Candida esophagitis . 33 women had vaginal infection, 25 had oral Candida, and 9 had esophageal infection with reduced CD4 counts . Infections of the oropharynx and the vagina are reduced CD4 counts . Infections of the oropharynx and the vagina are treated with amphotericin B, nystatin, miconazole, and clotrimazole . Systemically effective compounds include ketoconazole, itraconazole, and fluconazole, although interactions with rifampicin, phenobarbital, and phenytoin used in HIV treatment occur . Fluconazole is contraindicated in C . glabrata and C . krusei infections as it selects for azole-resistant Candida strains . Iv amphotericin B and fluconazole are used in serious infections when oral treatment is ineffective .

Carcinogenesis, 1992 May, 13(5), 783 - 6
Candida albicans as a promoter of oral mucosal neoplasia; O'Grady JF et al.; A model of oral mucosal carcinogenesis using the water-soluble carcinogen 4-nitroquinoline-1-oxide (4NQO) was combined with a model of oral mucosal candidosis to examine the ability of Candida albicans to promote the development of neoplasia in suitably initiated epithelium . Sprague-Dawley rats were initiated by the application of 4NQO to their palatal and tongue mucosa 3 times weekly for 4 weeks . The animals then received either application of a phorbol ester to act as a promoter, induction of experimental oral mucosal infection with C . albicans, or no further procedures . Animals were killed at 34 or 52 weeks and the tongues and palates sectioned for light-microscopic examination . Control groups with no treatment, mucosal infection only, phorbol ester application only, 4NQO with the tetracycline or vehicle application only were also used . The development of carcinoma in the experimental groups was similar to that in the positive control groups, indicating that the particular strain of Candida used had a similar ability to promote neoplastic changes as the known promoter phorbol-12,13-didecanoate and caused neoplastic changes to occur by week 34 with no additional lesions occurring by week 52 . This indicated that the speculation that strains of C . albicans may participate in causing neoplastic transformation in humans was well founded.

APMIS, 1992 May, 100(5), 393 - 400
Vaginal leukocyte characteristics in urogenital trichomoniasis; Buchvald D et al.; Morphological and functional characteristics of vaginal exudate leukocytes were examined in 47 patients with urogenital trichomoniasis . Electron microscopic morphology, viability, phagocytosis of Candida albicans blastospores and ability to undergo respiratory burst in the iodonitrotetrazolium reductase test were evaluated in these cells . Vaginal inflammatory leukocytes were almost exclusively polymorphonuclear neutrophils, and their concentration was positively correlated (r = 0.58; p less than 0.001) with the number of trichomonads in the exudate . Median leukocyte viability reached 39% and both phagocytic and tetrazolium reductase activities of these cells were significantly reduced in comparison with those of circulating polymorphonuclear leukocytes . Patients with a clinical picture of severe mucosal inflammation had significantly higher vaginal exudate leukocyte concentrations and viability than those without inflammatory signs . The possible role of vaginal leukocytes in the pathogenesis of urogenital trichomoniasis is discussed.

Mol Cell Biol, 1992 May, 12(5), 1977 - 85
A G-protein alpha subunit from asexual Candida albicans functions in the mating signal transduction pathway of Saccharomyces cerevisiae and is regulated by the a1-alpha 2 repressor; Sadhu C et al.; We have isolated a gene, designated CAG1, from Candida albicans by using the G-protein alpha-subunit clone SCG1 of Saccharomyces cerevisiae as a probe . Amino acid sequence comparison revealed that CAG1 is more homologous to SCG1 than to any other G protein reported so far . Homology between CAG1 and SCG1 not only includes the conserved guanine nucleotide binding domains but also spans the normally variable regions which are thought to be involved in interaction with the components of the specific signal transduction pathway . Furthermore, CAG1 contains a central domain, previously found only in SCG1 . cag1 null mutants of C . albicans created by gene disruption produced no readily detectable phenotype . The C . albicans CAG1 gene complemented both the growth and mating defects of S . cerevisiae scg1 null mutants when carried on either a low- or high-copy-number plasmid . In diploid C . albicans, the CAG1 transcript was readily detectable in mycelial and yeast cells of both the white and opaque forms . However, the CAG1-specific transcript in S . cerevisiae transformants containing the C . albicans CAG1 gene was observed only in haploid cells . This transcription pattern matches that of SCG1 in S . cerevisiae and is caused by a1-alpha 2 mediated repression in diploid cells . That is, CAG1 behaves as a haploid-specific gene in S . cerevisiae, subject to control by the a1-alpha 2 mating-type regulation pathway . We infer from these results that C . albicans may have a signal transduction system analogous to that controlling mating type in S . cerevisiae or possibly even a sexual pathway that has so far remained undetected.

J Bacteriol, 1992 May, 174(9), 2951 - 7
Genetics of the white-opaque transition in Candida albicans: demonstration of switching recessivity and mapping of switching genes; Chu WS et al.; Spheroplast fusion has been used to analyze the genetics of the reversible phenotypic transition, white-opaque, in Candida albicans WO-1 . This transition involves changes in cell shape, permeability, and colony morphology . Fusion of switching with nonswitching cells gave nonswitching fusants, suggesting that the white-opaque phenotype is recessive . Chromosome loss induced by heat shock gave segregants of the fusants which were able to undergo the transition, indicating that the repressor function is genetically defined and probably limited to one or two chromosomes . Chromosomes R, 1, 3, 4, and 7 were eliminated as unique sites for the repressor, leaving 2, 5, and 6 as possible locations . When a ura3 (chromosome 3) nonswitching strain was fused with a switching strain, all ura3 segregants induced by heat shock were incapable of the phenotypic transition . Therefore, some or all of the genes (called SWI genes) essential for the transition are located on chromosome 3 . UV irradiation-induced recombination did give rise to Ura- switching progeny, showing that the failure to switch was not due to a side effect of the pyrimidine requirement . The failure to isolate normally switching ura3 progeny generated by UV irradiation suggests a close linkage between the two genes.

Infect Immun, 1992 May, 60(5), 1972 - 8
Evidence that Candida albicans binds via a unique adhesion system on phagocytic cells in the marginal zone of the mouse spleen; Kanbe T et al.; We recently demonstrated by using an ex vivo adhesion assay that Candida albicans yeast cells exhibit a unique binding affinity for the marginal zone of the spleen . This binding event provides a working model for studying mechanisms of organ dissemination of the fungus from the blood . By using the ex vivo assays reported here, we showed by bright-field and electron microscopic techniques that mouse spleen marginal zone cells capable of ingesting India ink particles are also involved in yeast cell attachment . During splenic clearance of yeast cells from the circulation in vivo, C . albicans is also associated exclusively with marginal zone cells capable of ingesting India ink . The ability to ingest the ink particles is not necessarily related to yeast cell adherence, because the fungal cells did not bind to phagocytic cells in the splenic red pulp . In fact, the marginal zone phagocytic cells appear to have a unique binding system, because yeast cells also did not bind to phagocytes in other tissues, such as the thymus and peritoneum, or to seven different myeloid cell lines . In addition, antibodies to a number of well-characterized murine adhesion molecules, such as leukocyte integrins, LECAM-1, and CD44, had no effect on binding . On the basis of these results, we propose that splenic marginal zone phagocytes express a novel adhesion system that involves either a unique adhesion molecule or previously described adhesion molecules with unique binding activities.

Infect Immun, 1992 May, 60(5), 1927 - 35
Effect of in vivo administration of recombinant murine gamma interferon on in vitro lymphoproliferative responses following immunization with Candida albicans; Garner RE et al.; The effect of in vivo administration of recombinant murine gamma interferon (rMuIFN-gamma) on in vitro proliferation of lymphocytes to Candida antigens and lectins was examined in naive CBA/J mice and in similar mice colonized with Candida albicans by intragastric (i.g.) intubation and/or inoculated intradermally (i.d.) with the fungus . Lymph node lymphocyte and splenic lymphocyte (splenocyte) responses to soluble cytoplasmic substances derived from C . albicans varied with the route of inoculation of the fungus, the sex of the animal, and the presence or absence of rMuIFN-gamma treatment . In the absence of rMuIFN-gamma treatment, lymphoid cells from lymph nodes draining the site of the i.d . lesion responded well to soluble cytoplasmic substances . Colonization of the gut of female mice with C . albicans either had no effect or promoted better lymph node responses when such animals were also challenged i.d., whereas gut colonization of males followed by i.d . challenge appeared to have a suppressive influence on the level of proliferation in response to antigens in vitro . Antigen-specific splenocyte responses could be detected as well, and they were best in animals inoculated i.g.-i.d . or i.d . only . With the exception of lymph node lymphocytes from male mice, treatment of infected animals, regardless of the route of infection, with rMuIFN-gamma frequently resulted in lowered responses to antigens when comparable treatment groups were examined . With respect to mitogen stimulation, infection with C . albicans, especially i.g . or i.g.-i.d., resulted in a population of lymph node lymphocytes with lower-than-normal responses to concanavalin A but higher-than-normal responses to lipopolysaccharide (LPS) . Splenocyte responses to mitogens were not altered as dramatically as the responses of lymph node lymphocytes, but splenocytes from female mice had a suppressed response regardless of the route of exposure to C . albicans, and those from mice which were maximally stimulated with C . albicans, i.e., inoculated i.g.-i.d., also had a suppressed response to concanavalin A . Treatment with rMuIFN-gamma either had no effect on the subsequent splenocyte responses or boosted subnormal mitogen responses toward the normal range . Collectively, these data illustrate that exposure to both C . albicans and rMuIFN-gamma influenced the responses to mitogen and C . albicans antigen of lymph node lymphocyte and splenocyte populations, as detected in vitro by lymphoproliferation . Treatment with rMuIFN-gamma often resulted in increased responsiveness to a B cell mitogen, LPS, and decreased responsiveness to a C . albicans antigen.

Can J Anaesth, 1992 May, 39(5 Pt 1), 509 - 11
Growth curves of Staphylococcus aureus, Candida albicans, and Moraxella osloensis in propofol and other media; Tessler M et al.; Propofol, 2,6 diisopropylphenol, in an emulsion formulation (Diprivan), has been associated with postsurgical infections caused by Staphylococcus aureus, Moraxella osloensis and Candida albicans . These organisms were individually inoculated into each of the following media: (1) the emulsion preparation of propofol, (2) Intralipid 10%, (3) pure 2,6 diisopropylphenol, and (4) trypticase soy broth (TSB) . The organisms were incubated and subcultured hourly for eight hours at room temperature . Propofol supported the growth of all three organisms, but for S . aureus and M . osloenis, the growth rate was slower in propofol than in TSB (P less than 0.05) . There was no difference between the growth rate of any organism in propofol than in Intralipid 10% . The authors conclude that propofol, in the emulsion formulation, supports bacterial growth and, therefore, must be prepared for administration in an aseptic manner . Also, by administering propofol soon after preparation, the risk of introduction of a significant inoculum to the patient will be reduced.

Int J Immunopharmacol, 1992 May, 14(4), 605 - 11
Immunomodulating properties of carbamazepine in mice; Pacifici R et al.; The protective effects of carbamazepine (CBZ) were studied in mice inoculated with Lewis Lung Carcinoma (3LL), Madison Lung Carcinoma (M109), L5178Y lymphoma, L1210 leukaemia and Candida albicans . There was no significant increase in survival time of mice treated with CBZ . However, CBZ, as well as its metabolite CBZ 10-11 epoxide (CBZ 10-11 EPOX), showed a significant increase in NK-cell activity . CBZ also produced a significant increase of phagocytosis and killing properties of PMNs . There was no significant difference in the stimulation of splenic lymphocyte blastogenesis by different concentrations of phytohaemagglutinina (PHA), observed between the controls and CBZ treated mice . The results demonstrate that the effect of chronic treatment with CBZ on the immune response is a complex phenomenon which remains a challenge for future research.

Oral Surg Oral Med Oral Pathol, 1992 May, 73(5), 559 - 63
Candida species and Candida albicans morphotypes in erythematous candidiasis; Crockett DN et al.; A group of full-denture-wearing patients with erythematous candidiasis was matched by age and sex with a group of healthy, full-denture-wearing persons who served as controls . In the group with erythematous candidiasis, clinical symptoms and signs of the disease were recorded . Denture hygiene and tobacco use were noted in both groups . Epithelial smears and imprint cultures were obtained from both groups from specified sites . Cultures were grown and subjected to species identification and C . albicans strain differentiation by a morphotyping technique . Denture-wearing subjects who smoked tobacco had a significantly greater incidence of erythematous candidiasis than the controls . Five species of Candida were isolated from both groups, with C . albicans as the dominant species . Twenty different morphotypes of C . albicans as well as strains involved in erythematous candidiasis were also isolated from the oral cavities of healthy, full-denture-wearing control subjects.

Pathol Biol (Paris), 1992 May, 40(5), 513 - 7
{Treatment and secondary prophylaxis with fluconazole for oropharyngeal candidiasis in HIV-positive patients . A mycological analysis of failures}; Reynes J et al.; This prospective study evaluated the in vitro susceptibility of Candida albicans isolates recovered from the oral cavity of AIDS/ARC patients before and during long-term therapy with fluconazole . Thirty adults (15 with ARC and 15 with AIDS) with a first episode of thrush candidiasis were given oral fluconazole (Triflucan 50 mg; one capsule daily) for at least three months . Fungal susceptibility testing was performed before treatment, after one month, and at last follow-up (range 3.5-12 months; mean 5.7 months) . MICs were determined using the agar dilution method with casitone (Difco 259-01) as the test medium at pH 7.2-7.4 . There were two initial clinical failures (one with high MICs before and under treatment and one with an intermediate MIC initially and a rise in MIC under fluconazole) . Four patients developed a clinical relapse with no change in MICs (which were low or intermediate) . In six patients, clinical symptoms resolved but carriage of C . albicans persisted (low MICs) . In 18 patients, clinical resolution with eradication of C . albicans was achieved . These data suggest that (1) clinical failures may be associated with in vitro resistance; (2) relapses under fluconazole maintenance therapy may develop in patients with advanced HIV disease despite the lack of change in the susceptibility of strains.

Pathol Biol (Paris), 1992 May, 40(5), 507 - 12
{Emulsion of amphotericin B in Intralipid 20%: in vitro and in vivo efficacy}; Chavanet P et al.; Toxic effects limit the use of amphotericin B (AmB) for the treatment of systemic Candida infections . In vitro and in vivo toxicity can be substantially reduced by mixing AmB with a lipid emulsion used for parenteral nutrition, intralipid 20% (IL) . This study was designed to evaluate the potential effects of IL on the activity of Amphotericin B against Candida . A clinical strain of Candida albicans was used . AmB deoxycholate (Fungizone) was reconstituted in a 5% glucoce solution (AmB-G5), in 3 mg/ml IL (AmB-IL3) or in 1.5 mg/ml IL (AmB-IL 1.5) . Minimum inhibitory concentrations and minimum lethal concentrations were 0.4 mg/l and 2.5 mg/l, respectively, with AmB-G5, 0.1 mg/l and 1 mg/l with AmB-IL3, and 0.24 mg/l and 1 mg/l with AmB-IL 1.5 . In vitro killing curves with 0.1 mg/l, 0.25 mg/l, and 2.5 mg/l AmB were determined with the following results: 1) with 0.1 and 0.25 mg/l AmB, fungicidal activity was seen with AmB-IL3 and AmB-IL 1.5 but not with AmB-G5; 2) with 2.5 mg/l AmB, fungicidal activity was less marked with AmB-G5 (-1.7 log CFU/ml after 24 hours) than with AmB-IL3 and AmB-IL1.5 (-4.3 log CFU/ml and -4.2 log CFU/ml, respectively, after 24 hours; p less than 0.05) . In rabbits given a single intravenous injection of 4 mg/kg AmB, analysis of infected subcutaneous fibrin clots detected measurable concentrations of AmB beyond the 24th-36th hour, with levels of 0.5 mg/l for AmB-G5 and 1 mg/l for the two AmB-IL preparations over a period of three days.(ABSTRACT TRUNCATED AT 250 WORDS)

Pathol Biol (Paris), 1992 May, 40(5), 500 - 6
{In vitro evaluation of the sensitivity to fluconazole of different species of yeasts isolated in pathology}; Regli P et al.; In a previous study, the authors developed a technique for evaluating the in vitro susceptibility (or resistance) of Candida albicans to fluconazole, using casitone broth and agar . Photometric readings of growth in liquid media proved more accurate for evaluating antifungal activity and consistently agreed with clinical findings in all studied cases . This method was consequently extended from C . albicans to other yeasts recovered from high-risk patients (C . glabrata, C . famata, C . tropicalis, C . krusei, C . pseudotropicalis, C . parapsilosis, etc...) . High resolution antifungal assay medium (broth and agar) and casitone medium (broth and agar) with or without agitation (Autobac System) were used to study the activity of fluconazole against approximately one hundred yeast strains . MICs above 3.12 micrograms/ml were found for several strains, particularly belonging to the C . glabrata and C . krusei species . These values are equal to or greater than serum levels achieved during treatment with fluconazole, a fact which raises practical questions concerning fluconazole therapy and may explain the failure of fluconazole to eradicate yeasts in some patients.

Pathol Biol (Paris), 1992 May, 40(5), 495 - 9
{Comparative study of two systems for the determination of the sensitivity of yeasts to antifungal agents}; de Montclos M et al.; One hundred yeast strains (including 60 Candida albicans) were tested in two laboratories using two different antifungal susceptibility test kits, ATB Fungus and Mycostandard . Tests were carried out under everyday work conditions . Four antifungal agents were compared: amphotericin B, flucytosine, miconazole, and ketoconazole . Results were discrepant in 19.2% (77/400) of cases . Following retesting of discordant cases with both kits, the agreement rate for strain characterization was 95.5% . Few discrepancies were seen with flucytosine . Conflicting results obtained with amphotericin B were due to poor reproducibility of Mycostandard results, especially for species other than C . albicans . In contrast, reproducibility of the ATB Fungus kit was inadequate for miconazole . The rate of discrepant results was greatest for ketoconazole . Intermediate susceptibility was seen more often with ATB Fungus for C . albicans and with Mycostandard for C . glabrata and C . krusei . The lack of reproducibility under routine working conditions should lead gallery manufacturers to strive to achieve clearer readings.

Mycoses, 1992 May-Jun, 35(5-6), 131 - 9
Candida albicans antifungal-resistant strains: studies on adherence and other pathogenicity related characteristics; Ghannoum MA; In search of adhesion-variant strains of Candida albicans the adherence of a number of polyenes and/or azole-resistant strains of this yeast was studied (C . albicans 6406, 6406/8 and 799-XL, -XS, -YS, -R and YL) . For comparison C . albicans KCCC 14172, known for its high adhesion and proteinase production, was also used . All isolates showed significantly lower adhesion (P < 0.001) compared with KCCC 14172 . The exception was 6406/8 which showed superior adherability to all strains tested (2.5-4.8 times more adherent) . This superiority prompted us to study the possible variation between this strain and the others in parameters that contribute to pathogenicity . Strain 6406/8 had the smallest average cell size (0.5-0.75 the size of cells from other strains) . Variation in proteinase production and germ-tube formation existed among strains, with strain 6406/8 producing the lowest levels of inducible proteinase (2-4-fold less than the others), as well as being the least germ-tube former (10 times less than other strains) . Ultrastructural comparisons between strain 6406/8 and its parent showed that the mutant strain had a thinner cell wall with a dense floccular layer throughout the cell wall compared to the parent strain . The cytoplasmic membrane of the mutant was more conspicuous than that of the parent strain . Comparison of the pathogenicity of strain 6406/8 and its parent (6406) revealed that although the mutant strain initially showed higher colonization than the parent strain, it was cleared much faster.(ABSTRACT TRUNCATED AT 250 WORDS)

Eur J Clin Microbiol Infect Dis, 1992 May, 11(5), 438 - 46
Evaluation of an enzyme immunoassay using neoglycolipids constructed from Candida albicans oligomannosides to define the specificity of anti-mannan antibodies; Faille C et al.; In order to study the respective roles of oligomannoside sequences in the antigenicity of Candida albicans phosphopeptidomannan, a method was developed for constructing neoglycolipids from oligomannosides released by depolymerisation of this molecule . Oligomannosides released by acetolysis were converted to neoglycolipids by coupling them to 4-hexadecylaniline in an equimolar reaction checked by thin layer chromatography . When coated onto microEIA plates, the neoglycolipids exhibited strong reactions which were dose dependent and were saturable with concanavalin A . Reactivity of neoglycolipids with immunoglobulins were then tested with a panel of monoclonal and polyclonal antibodies reacting with epitopes present in the original phosphopeptidomannan . One of two IgM monoclonal antibodies and two of five monospecific rabbit polyclonal IgG reacted strongly with neoglycolipids therefore providing evidence of the presence of structures mimicking epitopes within the pool of neoglycolipids . When 38 sera from 18 hospital inpatients with various levels of antibodies to Candida albicans were tested, a correlation was observed between the EIA to detect neoglycolipids and the EIA to detect phosphopeptidomannan . Successive sera from all patients showing seroconversion in the immunofluorescence assay had increased EIA signals for neoglycolipids.

Eur J Clin Microbiol Infect Dis, 1992 May, 11(5), 395 - 402
Efficacy of fluconazole in the treatment of systemic fungal infections; Milatovic D et al.; The efficacy of fluconazole in the treatment of systemic fungal infections was evaluated in an open non-comparative trial . A total of 48 patients with proven or suspected fungal infections were enrolled in 40 of whom efficacy was evaluable . Candida albicans accounted for 90% of the infections . Candida parapsilosis, Candida glabrata, Histoplasma capsulatum and Aspergillus fumigatus caused the infection in one case each . Fluconazole was administered at a dosage of 200-400 mg daily for a mean duration of 15 days . Fluconazole treatment was successful in 53% of the patients . In patients with proven or probable Candida albicans infections a clinical and mycological response was achieved in 62% and 65%, respectively . In 11 patients elevation of liver enzymes was considered to be possibly related to fluconazole treatment; modification of treatment was not necessary in any case . Fluconazole was found to be a well tolerated and effective agent for the treatment of systemic Candida albicans infections.

Trans R Soc Trop Med Hyg, 1992 May-Jun, 86(3), 317 - 20
Causes of conjunctivitis and keratoconjunctivitis in Karachi, Pakistan; Woodland RM et al.; The causes of conjunctivitis and keratoconjunctivitis in 388 patients who attended eye casualty departments in Karachi, Pakistan, during a 5 month period were investigated . Most of these infections were diagnosed as adenovirus (291, 75%) or bacterial (71, 18.3%) . Of the remainder, 9 cases (2.3%) were caused by herpes simplex virus and 7 (1.8%) by Chalmydia trachomatis . There was no evidence of typical active trachoma in this urban population . Bacteria or Candida albicans were also grown from 44 of the adenovirus cases (15%) . Many of the bacteria grown from eyes in this study were resistant to antibiotics, probably because of inadequate and/or inappropriate self-medication with antibiotics in this community.

Eur J Epidemiol, 1992 May, 8(3), 350 - 5
Inhibition of adherence of Candida albicans to acrylic by a chitin derivative; Segal E et al.; The purpose of this study was to assess the effect of a chitin derivative (CSE) on the adherence of Candida albicans to acrylic . Fungal adherence to acrylic dentures is considered an essential step in the development of denture stomatitis . Adherence of C . albicans to acrylic pieces (5 x 5mm) was assessed microscopically using a calibrated ocular objective and expressed as number of adherent yeasts/mm2 of acrylic . CSE was prepared from commercial chitin (crab shell) and from chitin isolated from C . albicans blastospores . The effect of both CSE types on the adherence of C . albicans to acrylic was examined in two experimental systems: CSE present during the adherence assay and acrylic pieces pretreated with CSE prior to the assay . Both CSE types exerted a significant inhibitory effect when tested in the two experimental systems . These findings are significant for possible prevention of denture stomatitis.

Eur J Pediatr, 1992 May, 151(5), 344 - 6
Exophiala dermatitidis pneumonia in cystic fibrosis; Kusenbach G et al.; The chest X-ray film of a girl with cystic fibrosis (CF) showed slowly increasing mottled densities during the 6th and 7th year of her life . Pulmonary symptoms and distress proceeded fast in spite of intensive treatment with antibiotics, corticosteroids, and physiotherapy . Three different fungal organisms were repeatedly cultured from the sputum: Candida albicans, Aspergillus fumigatus, and Exophiala dermatitidis . Antibodies against C . albicans were in the normal range . Candida antigen in blood and antibodies against A . fumigatus were absent . Antibodies against E . dermatitidis were detected by a recently developed indirect immunofluorescence assay . It seems most probable that E . dermatitidis was the causal agent for fungal pneumonia in this case . Under therapy with amphotericin B and flucytosine the clinical course and radiological appearance improved but definitive eradication of E . dermatitidis was only achieved after treatment with itraconazole . The isolation of this fungus from the sputum of a CF patient is reported for the first time . The significance of fungal infections in CF is discussed.

J Burn Care Rehabil, 1992 May-Jun, 13(3), 323 - 9
Candida albicans growth studies: a hypothesis for the pathogenesis of Candida infections in burns; Neely AN et al.; The proteolytic environment in which Candida albicans exists strongly affects its virulence . To determine whether virulence might be related to C . albicans growth in different proteolytic environments, we measured renal fungal load in burned mice and found significantly greater Candida census in kidneys from mice that were challenged with a high proteinase-generating parent C . albicans (MY 1044) versus those that were challenged with its low proteinase-generating mutant (MY 1049) . In vitro, MY 1044 cells grew faster than MY 1049 cells in media that contained sera from burned mice as the only nitrogen source . Augmentation of media with proteinase or a mixture of amino acids increased growth of MY 1049 cells, whereas augmentation with proteinase inhibitor decreased MY 1044 growth . In conclusion, in vitro growth of both the mutant and its parent strain was affected by the proteolytic environment in which they existed; thus, virulence differences for MY 1044 and MY 1049 could be due in part to growth differences between these two strains in different proteolytic environments . These results were combined with existing observations, and we proposed a theory for the pathogenesis of C . albicans in burns.

Infect Immun, 1992 May, 60(5), 2106 - 9
Evidence for oligomannosyl residues containing both beta-1,2 and alpha-1,2 linkages as a serotype A-specific epitope(s) in mannans of Candida albicans; Kobayashi H et al.; In order to identify the branches containing both beta-1,2 and alpha-1,2 linkages as the serotype A-specific epitope(s) in the mannans of Candida albicans, serotype A strains with oligosaccharides constituting the beta-1,2 linkage, the alpha-1,2 linkage, and both the beta-1,2 and the alpha-1,2 linkages were prepared from the mannans of C . albicans serotype A strains (NIH A-207 and J-1012) and tested for their inhibitory effects in the precipitin and slide agglutination assays . The results indicated that two oligosaccharides containing both beta-1,2 and alpha-1,2 linkages, Manp beta 1-2Manp alpha 1-2Manp alpha 1-2Manp alpha 1-2Man and Manp beta 1-2Manp beta 1-2Manp alpha 1-2Manp alpha 1-2Manp alpha 1-2Man, served as epitopes participating in the serotype A specificity of C . albicans strains.

Eur J Epidemiol, 1992 May, 8(3), 368 - 76
Antigen-specific cytolysis of infected cells in murine candidiasis; Romani L et al.; Immune L3T4+ and Lyt-2+ lymphocytes play an important role in the acquired resistance of mice to challenge with virulent Candida albicans, and release macrophage-activating cytokines in response to yeast cells in vitro . To determine whether antigen (Ag)-specific cytotoxic T lymphocytes are generated during fungal infection, purified L3T4+ and Lyt-2+ lymphocytes from immunized mice were cultured in the presence of syngeneic accessory cells, Candida Ag, and IL-2 . Yeast-infected bone marrow macrophages and peritoneal exudate neutrophils were used as target cells in a standard 51Cr release assay . Ag-specific, MHC-unrestricted lysis of infected macrophages was evident with immune Lyt-2+ cells after 5-10 days in culture . Under the same experimental conditions, the cytotoxic activity of L3T4+ cells was negligible, but its expression could be induced by the addition of anti-CD3 antibody . Culturing immune Lyt-2+ cells for shorter periods of time (1-2 days) resulted in preferential lysis of infected neutrophils . In addition, at limiting effector cell numbers, Ag-specific MHC-restricted lymphocytes with cytotoxic activity to infected macrophages could be identified . We suggest that C . albicans infection stimulates multiple cytotoxic T-cell precursors with varying recognition stringency, which may have an important role in antifungal resistance in vivo.

Eur J Epidemiol, 1992 May, 8(3), 362 - 7
The secretion of aspartyl proteinase, a virulence enzyme, by isolates of Candida albicans from the oral cavity of HIV-infected subjects; De Bernardis F et al.; Prevalence, serotype and in vitro secretion of aspartyl proteinase, a virulence enzyme, were studied in Candida isolates from the oral cavity of 337 HIV-infected subjects . Controls were 95 age-sex-matched HIV- (seronegative) subjects, belonging to either HIV-risk categories (47) or to the normal, general population (48) . Fungi were isolated from 155 HIV+ subjects . C . albicans was the most prevalent species (85.8% of all isolates) . 94.6% of C . albicans isolates were serotype A and all were agglutinated by a monoclonal antibody (AF1) directed against a major mannoprotein immunogen of the candidal cell wall, confirming previous results with C . albicans isolates from non-immunodeficient subjects . With regard to the stage of HIV infection, there were no statistically significant differences in the incidence of oral Candida carriage between asymptomatic (stage II) HIV+ and HIV- subjects, and between stage II and lymphadenopathic (stage III) individuals . Also, the low (3.8%) incidence of oral candidiasis in the subjects of the latter stage was insignificant with respect to stage II subjects . However, the incidence of C . albicans in stage IV (AIDS) subjects (46.8%) was significantly higher than in all other subjects, and in almost all cases, fungal isolation was accompanied by oral thrush and lower CD4+ lymphocyte counts (less than 400 x 10(6)/L) . All isolates of C . albicans were proteolytic in vitro, as assessed by scoring the proteinase activity on BSA agar and monitoring the secreted proteinase antigen by a highly sensitive (1 ng) and specific immunoenzymatic assay.(ABSTRACT TRUNCATED AT 250 WORDS)

J Gen Microbiol, 1992 May, 138 ( Pt 5), 901 - 7
The molecular analysis of synonymy among medically important yeasts within the genus Candida; Wickes BL et al.; Three sets of medically important yeasts, Candida albicans, C . tropicalis, and C . krusei, were compared with their putative synonyms (C . langeronii and C . claussenii, C . paratropicalis, and Itssatchenkia orientalis, respectively) to determine if these synonyms are genetically distinguishable from each other . Pulsed-field electrophoresis and hybridization to species-specific probes were used to accomplish this goal . The species-specific probes for C . albicans and C . tropicalis have been previously described (27A and CT13.8, respectively) whereas the probe for C . krusei (CK3) was cloned in this study . No distinguishing characteristics between synonyms were identified, thus supporting the current taxonomic treatment of these organisms.

J Biol Chem, 1992 Apr 25, 267(12), 8591 - 8
The Candida albicans myristoyl-CoA:protein N-myristoyltransferase gene . Isolation and expression in Saccharomyces cerevisiae and Escherichia coli; Wiegand RC et al.; Myristoyl-CoA:protein N-myristoyltransferase (NMT) has recently been identified as a target for antiviral and antifungal therapy . Candida albicans is a dimorphic, asexual yeast that is a major cause of systemic fungal infections in immunosuppressed humans . Metabolic labeling studies indicate that C . albicans synthesizes one principal 20-kDa N-myristoyl-protein . The single copy C . albicans NMT gene (ca-NMT1) was isolated and encodes a 451-amino acid protein that has 55% identity with Saccharomyces cerevisiae NMT . C . albicans NMT1 is able to complement the lethal phenotype of S . cerevisiae nmt1 null mutants by directing efficient acylation of the approximately 12 endogenous N-myristoylproteins produced by S . cerevisiae . C . albicans NMT was produced in Escherichia coli, a prokaryote with no endogenous NMT activity . In vitro studies of purified E . coli-derived S . cerevisiae and C . albicans NMTs revealed species-specific differences in the kinetic properties of synthetic octapeptide substrates derived from known N-myristoylproteins . Together these data indicate that C . albicans and S . cerevisiae NMTs have similar yet distinct substrate specificities which may be of therapeutic significance.

Nucleic Acids Res, 1992 Apr 11, 20(7), 1705 - 10
Isolation and sequence analysis of the gene for translation elongation factor 3 from Candida albicans; Myers KK et al.; Elongation factor 3 (EF-3) is a unique and essential component of the translational system in fungi . The gene, CEF-3, encoding elongation factor 3 has been isolated from the dimorphic fungus Candida albicans . A heterologous gene probe containing the coding region of the EF-3 gene from Saccharomyces cerevisiae (YEF-3) was used to screen three Candida albicans genomic DNA libraries . The nucleotide sequences of four partial clones were determined and combined for a full-length of 3,671 base pairs (bp) . A continuous open reading frame (ORF) of 3,147 bp encoding a predicted protein of 1,049 amino acids and Mr of 116,739 daltons has been identified . A transcript of 3,400 nucleotides is seen in Northern blot hybridization of Candida albicans total RNA using a CEF-3 gene probe . The single locus CEF-3 gene maps to chromosome 5 in the genome . Comparison of the deduced amino acid sequences of CEF-3 and YEF-3 shows 77.6% . identity . A higher degree of identity, 86.5%, is found when comparing the carboxy-terminal portions of the two proteins . At the nucleotide level, comparison of the coding regions of the two genes exhibit 79% identity while the upstream and downstream regions show 46% and 40% identity, respectively.

Kansenshogaku Zasshi, 1992 Apr, 66(4), 536 - 9
{A case of Candida albicans endocarditis with impaired lung function}; Yamamoto W et al.; A 53-year-old male was admitted to the hospital because of Candida albicans endocarditis . He had had a thoracoplasty due to pulmonary tuberculosis and showed severe restructive lung function . In 1987 and '89, trachiostomy was made because of respiratory failure . The patient was well until nine months earlier, when he consulted a physician because of fever . The investigations failed in finding the cause of the fever . He was administered antituberculosis agents and antiinflammatory drugs but had a fever every day . Two months before admission, a cardiac ultrasonographic study showed evident vegetations with mitral regurgitation . From the above course and examinations, a diagnosis of Candida albicans endocarditis was made . Infusions of CEZ, TOB, PIPC and miconazole for more than one month was ineffective . In November, 1990, he was referred to our medical center for the purpose of operation . A blood culture proved Candida albicans infection . An intravenous administration of fluconazole 400 mg/day was begun . However, there was pulmonary bleeding probably due to heparin used for prevention of atrial thrombosis and he developed fever, hypoexemia, ventricular tachycardia, and hyponatremia . He underwent mitral-valve replacement with a SJM valve . Culture of the vegetated mitral valve again proved Candida albicans . After operation, hypoexemia, ventricular tachycardia, hyponatremia were improved gradually . However he had an eosinophilia, eruption, and dyspnea . We suspected a drug eruption of fluconazole . Lymphocyte stimulating test of fluconazole proved positive . After the episode, he had no symptoms and was discharged.

Kansenshogaku Zasshi, 1992 Apr, 66(4), 516 - 21
{Studies on the effect of combination of amphotericin B and flucytosine on Candida albicans by flow cytometry}; Taguchi H et al.; The antifungal effects of amphotericin B (AMPH) and flucytosine (5-FC) on three strains of Candida albicans were studied by flow cytometry (FCM) . When the IFM4954 and IFM4949 were treated with AMPH or 5-FC alone, cytograms of cell distribution changed at the concentration of 1/2 MIC, respectively . Next, the effect of combination of AMPH and 5-FC were examined . Cytogram of cell distribution of IFM4954 and IFM4949 changed under the combination of 1/4 MIC of AMPH and 1/4 MIC of 5-FC, namely a synergic effect was observed . In conclusion, FCM is a useful apparatus for analysis of the effect of antifungal agents.

Pediatr Pulmonol, 1992 Apr, 12(4), 240 - 6
Technique and use of transbronchial biopsy in children and adolescents; Whitehead B et al.; Since July 1988, a total of 92 transbronchial biopsies (TBB) have been performed in 18 patients (aged 3-16 years) . Twelve patients (67%) were heart-lung transplant (HLT) recipients undergoing surveillance for pulmonary graft rejection and infection . The remainder included immunocompromised patients at risk of opportunistic infections (n = 4), patients with fibrosing alveolitis (n = 1) and a collagen vascular disorder with suspected lung involvement (n = 1) . TBB was performed through either a fiberoptic (n = 50) or a rigid (n = 41) bronchoscope, all under general anesthesia . On one occasion a cardiac bioptome was used through an endotracheal stent . The sensitivity of TBB for diagnosing acute and chronic rejection in HLT patients was 88% and 60%, respectively (specificity, 91% and 100%) . Definitive diagnoses were made in 4 (67%) of the non-HLT group . Bronchoalveolar lavage (BAL) was performed during each procedure for microbiological and cytological examination . Thirty-four pathogenic organisms including Pseudomonas aeruginosa (16/34), Staphylococcus aureus (8/34), and Candida albicans (5/34) were isolated from BAL culture . Complications included pneumothorax (8%), transient pyrexia (7%), and dyspnea (2%).

Enferm Infecc Microbiol Clin, 1992 Apr, 10(4), 195 - 9
{Standardized immunoenzyme analysis for detection of IgG antibodies against Candida albicans in systemic candidiasis}; Carceller A et al.; We evaluate the usefulness of an ELISA test for detecting IgG antibodies against Candida albicans somatic and metabolic antigens . We studied 68 sera samples of patients with disseminated candidosis due to C . albicans in most of the cases . We used an ELISA test standardized with a monoclonal anti-IgG conjugate marked with peroxidase and soluble C . albicans antigens . We used as controls 84 sera from healthy individuals or patients without any evidence for disseminated candidosis . The maximum sensitivity for protein antigen of metabolic origin was 67.6%, with an specificity of 77.3% . For the somatic antigen, specificity was higher (83.3%) and positive predictive value was 0.741 . We believe that IgG-ELISA gives useful data for diagnosis and follow-up of patients with disseminated candidosis.

FEMS Microbiol Immunol, 1992 Apr, 4(4), 219 - 24
Antigenic heterogeneity of strains of Saccharomyces cerevisiae and Candida albicans recognised by serum antibodies from patients with Crohn's disease; McKenzie H et al.; The antigenic heterogeneity of twelve strains of Saccharomyces cerevisiae and serovar A and B strains of Candida albicans was investigated by cross-absorption of serum antibodies from a patient with Crohn's disease . On the basis of common antibody absorption patterns, eleven of the yeast strains were divided into Group 1 (five S . cerevisiae), Group 2 (two C . albicans, one S . cerevisiae) and Group 3 (three S . cerevisiae) . The remaining three S . cerevisiae strains (Group 4) showed unique absorption patterns . The antigenic relationship between S . cerevisiae and C . albicans was further studied by cross-absorption of sera from eight patients with Crohn's disease . This confirmed a limited degree of cross-reaction between most strains of S . cerevisiae and C . albicans, but C . albicans serovar B significantly absorbed antibodies to more S . cerevisiae strains than did C . albicans serovar A . The results demonstrate considerable antigenic heterogeneity of S . cerevisiae and suggest that the elevated serum antibody levels to S . cerevisiae found in Crohn's disease are directed against multiple antigens.

Mol Microbiol, 1992 Apr, 6(8), 1025 - 33
Elongation factor 3 (EF-3) from Candida albicans shows both structural and functional similarity to EF-3 from Saccharomyces cerevisiae; Colthurst DR et al.; As with many other fungi, including the budding yeast Saccharomyces cerevisiae, the dimorphic fungus Candida albicans encodes the novel translation factor, elongation factor 3 (EF-3) . Using a rapid affinity chromatography protocol, EF-3 was purified to homogeneity from C . albicans and shown to have an apparent molecular mass of 128 kDa . A polyclonal antibody raised against C . albicans EF-3 also showed cross-reactivity with EF-3 from S . cerevisiae . Similarly, the S . cerevisiae TEF3 gene (encoding EF-3) showed cross-hybridization with genomic DNA from C . albicans in Southern hybridization analysis, demonstrating the existence of a single gene closely related to TEF3 in the C . albicans genome . This gene was cloned by using a 0.7 kb polymerase chain reaction-amplified DNA fragment to screen to C . albicans gene library . DNA sequence analysis of 200 bp of the cloned fragment demonstrated an open reading frame showing 51% predicted amino acid identity between the putative C . albicans EF-3 gene and its S . cerevisiae counterpart over the encoded 65-amino-acid stretch . That the cloned C . albicans sequence did indeed encode EF-3 was confirmed by demonstrating its ability to rescue an otherwise non-viable S . cerevisiae tef3:HIS3 null mutant . Thus EF-3 from C . albicans shows both structural and functional similarity to EF-3 from S . cerevisiae.

Lymphokine Cytokine Res, 1992 Apr, 11(2), 95 - 8
The deleterious effect of macrophage colony-stimulating factor (CSF-1) on the pathology of experimental candidiasis in mice; Hume DA et al.; Mice infected with Candida albicans albicans intravenously were treated before or after infection with macrophage colony-stimulating factor (CSF-1) to elevate their circulating monocyte and tissue macrophage counts . Both treatments exacerbated the disease, causing a doubling of the rate of weight loss and leading to significantly earlier death . The results suggest that macrophages play a major role in the pathology of the disease.

Clin Microbiol Rev, 1992 Apr, 5(2), 183 - 203
High-frequency switching in Candida albicans; Soll DR; Most strains of Candida albicans are capable of switching frequently and reversibly between a number of phenotypes distinguishable by colony morphology . A number of different switching systems have been defined according to the limited set of phenotypes in each switching repertoire, and each strain appears to possess a single system . Switching can affect many aspects of cellular physiology and morphology and appears to be a second level of phenotypic variability superimposed upon the bud-hypha transition . The most dramatic switching system so far identified is the "white-opaque transition." This system dramatizes the extraordinary effects switching can have on the budding cell phenotype, including the synthesis of opaque-specific antigens, the expression of white-specific and opaque-specific genes, and the genesis of unique cell wall structures . Switching has been demonstrated to occur at sites of infection and between episodes of recurrent vaginitis, and it may function to generate variability in commensal and infecting populations for adaptive reasons . Although the molecular mechanisms involved in the switch event are not understood, recent approaches to its elucidation are discussed and an epigenetic mechanism is proposed.

Clin Infect Dis, 1992 Apr, 14(4), 884 - 8
Candidal pancreatic abscesses: report of two cases and review; Keiser P et al.; Pancreatic abscess caused by Candida albicans is very rare . To date, only eight case reports describing a pancreatic abscess caused wholly or in part by Candida species have appeared in the literature . We recently treated two patients with candidal pancreatic abscesses . In our cases as well as those reported in the literature, treatment of the abscess with antifungal agents was delayed because of failure to recognize Candida albicans as a pathogen . Effective treatment appears to consist of drainage of the abscess and administration of amphotericin B.

J Clin Microbiol, 1992 Apr, 30(4), 935 - 41
Genetic similarity and maintenance of Candida albicans strains from a group of AIDS patients, demonstrated by DNA fingerprinting; Schmid J et al.; By using the computer-assisted Dendron system to analyze the patterns of Southern blots probed with the repetitive sequence Ca3, we have compared oral isolates of Candida spp . from a group of 11 nonhospitalized patients with AIDS suffering from recurrent episodes of oral thrush in Leicester, England, with oral isolates from a group of control individuals . Genetic diversity among the AIDS strains was significantly reduced compared with that of control strains . In addition, the same strains persisted through recurrent infections in patients with AIDS . Although AIDS strains were genetically less diverse than either control strains or oral commensal strains analyzed in previous studies, the majority did not form a genetically distinct group . The results of this study suggest that in the majority of patients with AIDS in this group from Leicester, original commensal strains were replaced, replacement occurred early in the manifestation of AIDS, and replacement occurred only once.

Gene, 1992 Apr 1, 113(1), 125 - 7
Cloning and sequence analysis of a rapamycin-binding protein-encoding gene (RBP1) from Candida albicans; Ferrara A et al.; Rapamycin (Rm) and FK506 are macrolide antifungal agents that exhibit potent immunosuppressive properties in higher eukaryotes which are mediated through interaction with specific receptor proteins (FKBPs or RBPs, for FK506- and Rm-binding proteins, respectively) . These proteins possess peptidyl-prolyl cis-trans isomerase (PPIase) activity in vitro which is inhibited by the binding of Rm and FK506 . We previously isolated a gene encoding an RBP from Saccharomyces cerevisiae, and demonstrated that null mutations in this gene (called RBP1) result in a recessive Rm-resistant (RmR) phenotype . We now have cloned the Candida albicans RBP1 gene via complementation of the RmR phenotype in S . cerevisiae . The predicted C . albicans RBP exhibits 61%, 52% and 49% amino acid (aa) sequence identity with RBPs (FKBPs) from S . cerevisiae, Neurospora crassa and human cells (FKBP-12), respectively . Furthermore, several of the aa residues identified as being important for drug binding in human FKBP-12 are conserved within the C . albicans RBP.

Comp Immunol Microbiol Infect Dis, 1992 Apr, 15(2), 131 - 6
Effect of aztreonam upon human polymorphonuclear leukocyte functions; Rodriguez AB et al.; Aztreonam (SQ 26,776), a new synthetic monobactam with an excellent antibacterial spectrum was analyzed in vitro . In this paper, the effect of aztreonam on the phagocytic process of human neutrophils isolated from fifteen healthy volunteers was studied . Chemotaxis was not modified with aztreonam at any of the doses used (10, 20, 40, 60, 80 and 100 micrograms/ml) . On the other hand, this antibiotic at 100 micrograms/ml significantly increases (P less than 0.05) Candida albicans ingestion as well as their digestion by neutrophils at 10 and 100 micrograms/ml.

Infect Immun, 1992 Apr, 60(4), 1550 - 7
Identification of Candida albicans antigens reactive with immunoglobulin E antibody of human sera; Ishiguro A et al.; Candida albicans antigens which reacted with immunoglobulin E (IgE) antibodies of 57 allergic patients were detected by immunoblotting . Of the various antigens, the 175-, 125-, 46-, 43-, and 37-kDa antigenic components reacted most frequently with the patient sera . To purify the major antigens, C . albicans cells were fractionated . The 46-, 43-, and 37-kDa antigens were recovered in cytoplasmic fractions, but the 175- and 125-kDa antigens were not recovered in any fraction . The 46-, 43-, and 37-kDa antigens were purified from cytoplasmic fractions by DEAE and P11 ion-exchange chromatography . Antigens were isolated by cutting bands out of sodium dodecyl sulfate-polyacrylamide gels . The purified components confirmed by immunoblotting were next processed for amino acid sequencing . Parts of the sequences of the 46-, 43-, and 37-kDa antigens had significant levels of homology with Saccharomyces cerevisiae glycolytic enzyme enolase, phosphoglycerate kinase, and aldolase, respectively . Rabbit IgG antibodies prepared against the 46- and 43-kDa antigens strongly cross-reacted with the homologous proteins of S . cerevisiae . However, S . cerevisiae enolase and phosphoglycerate kinase did not cross-react with IgE of patient sera . This result suggests that IgE antibodies against only small parts of their epitopes are elevated in the allergic patients . Since enolase is reported to be a major antigen for systemic candidiasis, this enzyme may be the immunodominant protein in both allergies and fungal infections.

Infect Immun, 1992 Apr, 60(4), 1499 - 508
Hydrophobic surface protein masking by the opportunistic fungal pathogen Candida albicans; Hazen KC et al.; Ultrastructural and biochemical analyses of hydrophobic and hydrophilic yeast cell surface proteins of Candida albicans were performed . Hydrophobic and hydrophilic yeast cells were obtained by growth at 23 and 37 degrees C, respectively . In addition, hydrophilic yeast cells were converted to surface hydrophobicity by treatment with tunicamycin and dithiothreitol . When freeze-etched cells were examined, the temperature-induced hydrophilic cells had long (0.198 micron), compact, evenly distributed fibrils while temperature-induced hydrophobic cells had short (0.085 micron), blunt fibrils . Hydrophobic microsphere attachment to the hydrophobic cells occurred at the basement of and within the short fibril layer . Dithiothreitol-induced hydrophobic cells had the long fibrils removed; tunicamycin-induced hydrophobic cells retained some of the long fibrils, but the fibrils were less compact and more aggregated than the untreated controls . These results suggest that the long fibrils prevent hydrophobic microsphere attachment to the hydrophobic area of the cell surface . This was confirmed by assessing the hydrophobic avidity of hydrophobic yeast cell populations differing in fibril density and arrangement . 125I-labelled surface proteins from hydrophobic and hydrophilic cells were compared after separation by hydrophobic interaction chromatography-high-performance liquid chromatography and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography . The yeast cell populations had hydrophilic proteins of similar molecular masses (greater than 200 kDa), but the hydrophilic cells possessed at least two additional proteins (ca . 63 and 69 to 71 kDa) . Hydrophobic surface proteins appeared to be similar . However, the amount of total radiolabelled hydrophobic proteins was approximately 10-fold higher for the hydrophobic cells than for the hydrophilic cells . This result agrees with the ultrastructural observations which showed that yeast cell surface hydrophobic proteins are masked by hydrophilic high-molecular-mass surface fibrils . Taken together, the data indicate that yeast cell hydrophobicity is not determined by differences in surface hydrophobic proteins but by the presence of hydrophilic, surface fibrils.

Arch Pharm (Weinheim), 1992 Apr, 325(4), 199 - 204
Researches on antibacterial and antifungal agents, XIV: Thiophene analogues of bifonazole; Stefancich G et al.; Some thiophene analogues of bifonazole have been synthesized by standard procedures and their antifungal activity has been tested against Candida albicans . Among test derivatives biphenyl-4-yl-5-chloro-thien-2-ylimidazol-1-ylmethane and its 5-deschlorothien-2-yl analogue resulted to be the most active . Their antifungal potency was almost comparable to that of control substances, such as miconazole, ketoconazole, and bifonazole . Replacement of benzene by the pyrrole ring in the biphenyl portion retained almost quantitatively the antifungal activity, whereas substitution with other azoles and with nitrogen alicyclic rings led always to less potent derivatives.

J Appl Bacteriol, 1992 Apr, 72(4), 335 - 40
Effects of chlorhexidine diacetate on Candida albicans, C . glabrata and Saccharomyces cerevisiae; Hiom SJ et al.; The effects of chlorhexidine diacetate (CHA) on Candida albicans, C . glabrata and wild-type and mannan, and permeability mutants of Saccharomyces cerevisiae have been studied . A CHA concentration of 10 micrograms/ml had little lethal activity against the Candida strains, but was more effective against S . cerevisiae . Concentrations of 100 and especially 1000 micrograms/ml brought about a much more rapid death of cells . 2-Mercaptoethanol enhanced the activity of CHA to some extent . Some of the mutant strains of S . cerevisiae were rather more sensitive than the wild-type strain . The age of cultures of C . albicans and C . glabrata influenced their response to CHA.

Mol Cell Probes, 1992 Apr, 6(2), 137 - 43
Detection of Pneumocystis carinii in a rat model of infection by polymerase chain reaction; Reddy LV et al.; The polymerase chain reaction (PCR) was employed to detect Pneumocystis carinii in organs of infected rats . Using a pair of oligonucleotides designed to the dihydrofolate reductase (DHFR) gene of rat P . carinii, specific amplification of an expected 415 bp region of P . carinii DHFR DNA of this organism was achieved, while no amplification occurred with the human, Candida albicans, and Mycobacterium avium and tuberculosis DNAs . Using rat P . carinii isolated from in vitro cultures and infected lung homogenates, the minimum detection level by PCR on an ethidium bromide gel was about 200 organisms and by Southern analysis with radiolabelled DHFR probe the detection level improved to 20 organisms . This level of sensitivity is sufficient to detect P . carinii specific band on the gel in infected rat lung and other organs . This PCR technique is potentially useful for detecting P . carinii in bronchoalveolar lavage (BAL) fluids of AIDS patients and for quantifying the organisms in tissues and in in vitro cultures where a high background with conventional stains makes it harder to determine the number of organisms.

Antimicrob Agents Chemother, 1992 Apr, 36(4), 898 - 901
In vitro studies of activities of some antifungal agents against Candida albicans ATCC 10231 by the turbidimetric method; Blanco MT et al.; Different criteria (the drug concentration which inhibited 50% of growth {IC1/2}, the lowest drug concentration at which growth was just less than 30% of that in a positive control well {IC30}, the visual inhibitory concentration {ICv}, and the minimum fungicidal concentration {MFC}) were applied to study the effects of some antifungal agents against Candida albicans . Amphotericin B, flucytosine, and bifonazole produced total growth inhibition . Clotrimazole, itraconazole, ketoconazole, and miconazole produced partial growth inhibition . The values of IC1/2 and IC30 were similar for all agents and avoided the problems of partial inhibition; the values of ICv and MFC were higher than those of IC1/2 and IC30.

Mycopathologia, 1992 Apr, 118(1), 15 - 21
In vitro activity of cloconazole, sulconazole, butoconazole, isoconazole, fenticonazole, and five other antifungal agents against clinical isolates of Candida albicans and Candida spp; Hernandez Molina JM et al.; The in vitro activity of several new imidazoles, cloconazole, sulconazole, butoconazole, isoconazole and fenticonazole, were compared with those of amphothericin B, flucytosine, and three azoles: econazole, miconazole and ketoconazole against isolates of pathogenic Candida . A total of 186 clinical isolates of 10 species of the genus Candida and two culture collection strains were tested by an agar-dilution technique . Isoconazole was the most active azole, followed by butoconazole sulconazole . Differences between some of the species in their susceptibility to the antifungal agents were noted . Sulconazole and cloconazole had the highest activity in vitro against 106 isolates of C . albicans . Butoconazole and isoconazole were also very active against isolates of C . albicans, and were the most active azole compounds against 80 isolates of Candida spp.

Med Trop (Mars), 1992 Apr-Jun, 52(2), 151 - 5
{Preliminary data on dermatomycoses in Ouagadougou (Burkina Faso)}; Guiguemde TR et al.; This study is a contribution to a best knowledge of mycosis in Burkina Faso where the data concerning these diseases are very old . It has been focused on the clinical and mycological features of the dermoskeloton mycosis through the consultations at the two offices of dermatology in the city of Ouagadougou . From April to October, 1990, 216 patients have been taken census of, and they have shown 265 lesions among which 143 mycosis of the skinfolds (54 p . cent), 45 onychomycosis (17 p . cent), 29 palmoplantar mycosis (11 p . cent), 24 mycosis of the glabrous skin (9 p . cent) and 24 mycosis of the scalp (9 p . cent) . From these 265 lesions we have isolated 156 strains of dermatophytes and 108 strains of candida . The species which have been seen more frequently are Candida albicans (30 p . cent), Trichophyton rubrum (19 p . cent), Trichophyton soudanense (13 p . cent) and Trichophyton tonsurans (8 p . cent) . This study has enabled the identification of some clinical features and some responsible agents of the dermatoskeloton mycosis in Ouagadougou . It will lay the foundation for further specific studies in the country.

Clin Exp Allergy, 1992 Apr, 22(4), 485 - 90
Characterization of a monoclonal antibody (P40) against the 68 kD major allergen of Penicillium notatum; Shen HD et al.; A monoclonal antibody (MoAb P40) against the 68 kD major allergen of Penicillium notatum (P . notatum) was obtained by immunizing the mouse with a crude extract of P . notatum . Analysed by two-dimensional gel electrophoresis and immunoblotting, P40 reacted with two different isoforms of the 68 kD component of P . notatum with pIs of 5.4 and 5.5 . In addition to P . notatum, P40 showed positive ELISA activity to Aspergillus fumigatus (A . fumigatus) but not to components of six other fungi including Alternaria porri, Cladosporium cladosporoides, Aureobasidium pullulans, Fusarium solani, Rhizopus arrhizus and Candida albicans . Analysed by ELISA, MoAb P40 also showed positive activity to two (P . frequentans and P . roseopurpureum) of the 10 other Penicillium species and two (A . terreus and A . flavus) of the four other Aspergillus species tested . SDS-PAGE and immunoblotting studies demonstrated P40 positive reactivity to components with MW of about 67 kD in all these Penicillium and Aspergillus species with positive ELISA activity to P40 . Furthermore, immunoblotting activity of MoAb P40 to the 67 kD component of A . niger was also observed . The epitope of the 68 kD allergen of P . notatum recognized by MoAb P40 was resistant to treatment of periodate oxidation with concentration of NaIO4 up to 20 mM . This MoAb may thus be useful in the characterization and purification of the 68 kD allergen from crude extracts, and in the molecular cloning of allergen genes.

Clin Exp Allergy, 1992 Apr, 22(4), 469 - 74
Crossreacting IgE antibodies to Pityrosporum ovale and Candida albicans in atopic children; Savolainen J et al.; Sera from 13 patients with positive Pityrosporum ovale skin prick test were analysed with IgE immunoblotting . Both P . ovale and Candida albicans antigens were used to reveal possible crossreactivity of these yeasts . Of the 13 sera, eight sera showed IgE binding to P . ovale and six sera to C . albicans . Simultaneous IgE-binding to both C . albicans and P . ovale was observed in five of these sera . The most common IgE-binding band pairs were, a 23 kD band of P . ovale and a 27 kD band of C . albicans, as one pair, and a 26 kD band and a 13 kD band, respectively, as another pair . In addition to these protein bands, simultaneous reactivity was observed to C . albicans mannan, a polysaccharide, and to a diffuse high molecular weight component of P . ovale, possibly also a polysaccharide . The five sera with simultaneous IgE-binding were analysed with RAST-inhibition, which revealed presence of crossreacting IgE-antibodies to P . ovale and C . albicans in two of these sera . Crossreacting epitopes were suggested to be located in the mannan polysaccharide of C . albicans and high molecular weight diffuse stain of P . ovale, based on the immunoblotting and RAST-inhibition patterns of the studied sera . Crossreacting sera were pooled and used as an IgE probe in CRIE and Tandem-CRIE . These experiments revealed a fused precipitin line indicating presence of a common structure of P . ovale and C . albicans . This suggested crossreactivity may imply an interesting phenomenon in atopics who are sensitized by C . albicans growth in the gastrointestinal tract and get exposed by P . ovale growing on the skin.(ABSTRACT TRUNCATED AT 250 WORDS)

Phytochemistry, 1992 Apr, 31(4), 1147 - 53
Structural study of cell wall mannan of a Candida albicans (serotype A) strain; Kobayashi H et al.; The structure of the mannan of Candida albicans NIH A-207 strain (serotype A) was investigated by adopting mild acetolysis followed by enzymolysis with an Arthrobacter GJM-1 exo-alpha-mannosidase . The resultant oligosaccharides, from pentaose to octaose (where manp = D-mannopyranose), were identified as manp beta (1----2)manp alpha (1----2)manp alpha (1----2)manp alpha (1----2)manp, manp beta (1----2)manp beta (1----2)manp alpha (1----2)manp alpha (1----2)- manp alpha (1----2)manp, manp beta (1----2)manp beta (1----2)manp beta (1----2)manp alpha (1----2)manp alpha (1----2)manp alpha (1----2)manp and manp beta (1----2)manp beta (1----2)manp beta (1----2)manp beta (1----2)manp alpha (1----2)manp alpha (1----2)manp alpha (1----2)manp, respectively . Analyses of alpha-linked oligosaccharides obtained by acetolysis under conventional conditions gave the same oligosaccharides, from biose to heptaose, as those obtained from the mannans of C . albicans NIH B-792 (serotype B) and J-1012 (serotype A, formerly serotype C).

Rev Latinoam Microbiol, 1992 Apr-Jun, 34(2), 101 - 6
Humoral response to blastospores and mycelium in mice injected with different doses of Candida albicans; Meson OE et al.; An indirect immunofluorescence assay was carry out to determine the IgM and IgG antibody responses to yeast and mycelial forms of Candida albicans in mice injected with a 5 x 5(5) and 5 x 10(7) live cells suspensions . Prior adsorption of the serum samples with heat-killed blastospores enabled us to follow the specific antimycelial response which were detected considerably later than expected . Slow level of antibodies were obtained within an infection of 5 x 10(5) cell for both antibody classes and for yeast and mycelial forms . When a 5 x 10(7) cell dose was used for inoculation, maximum titers of antibodies to blastospores and mycelium in non-adsorbed sera appeared almost simultaneously (days 15 and 13, respectively) . When serum samples from mice infected with the same dose were previously adsorbed with blastospores, the antimycelium antibodies for both types of Igs, were detected delayed during the infection course . In this case the higher titer for IgG appeared on day 33 and on day 23 for IgM . We suggest that the high titer obtained with the blastospore forms for the 5 x 10(7) cell dose may be due to a major immunogenicity of this forms, for to induce an immune response in the host, or that the delay in the antimycelium antibodies detection could be due to that a blastospore form is the predominant in the infection early stages . Implications of this fact for pathogenesis are discussed.

Antonie Van Leeuwenhoek, 1992 Apr, 61(3), 207 - 19
Isolation and characterization of respiration-deficient mutants from the pathogenic yeast Candida albicans; Hatab MA et al.; The isolation of several respiration deficient mutants of the pathogenic yeast Candida albicans is described . These show greatly reduced respiration rates, loss of cytochromes aa3 and b, and reduced growth rates . All of the mutants had lost the ability to assimilate a wide range of carbon sources . Ultrastructural studies showed reduced development of mitochondrial cristae in the mutants . The mutants can be divided into three classes depending on their respiration responses to the addition of cyanide.

Aust Dent J, 1992 Apr, 37(2), 107 - 14
Denture stomatitis--a review of the aetiology, diagnosis and management; Jeganathan S et al.; Denture stomatitis is a common recurring problem of the denture wearers . The aetiology of the disease includes infection, trauma and probably a defect in the host defence mechanism . Current thinking suggests an interplay of most of these factors in the pathogenesis of the disease . The extent of interplay of these factors is still a controversy . Candida albicans has been implicated as the causative organism . However, in the light of recent research it is debatable if it is the only causative organism . Recently, cases resistant to antifungal therapy have been reported . In such cases other micro-organisms have been isolated . At the moment, comprehensive management includes meticulous denture hygiene together with anti-fungal or antibacterial therapy and correction of denture faults.

J Infect Dis, 1992 Apr, 165(4), 761 - 4
Disseminated candidiasis due to amphotericin B-resistant Candida albicans; Conly J et al.; Although development of resistance in Candida albicans to amphotericin B is considered rare, C . albicans was persistently recovered from a 28-year-old man after a prolonged course of broad-spectrum antimicrobial therapy for a pancreatic abscess . Determination of the MICs of drugs for C . albicans in Sabouraud broth revealed MICs of 2.5 mg/l amphotericin B, greater than 40 mg/l ketoconazole, 2.5 mg/l miconazole, and greater than 40 mg/l 5-fluorocytosine . Synergy testing revealed a MIC of 0.3 mg/l amphotericin B in the presence of 2.5 mg/l 5-fluorocytosine . When intravenous 5-fluorocytosine was added to the patient's antifungal regimen, achieving levels of 125 mg/l, negative blood cultures resulted for the first time . This suggests there may be a clinical use for in vitro synergy testing as an adjunct to guide antifungal therapy for fungemia due to amphotericin B-resistant C . albicans.

Am J Ophthalmol, 1992 Mar 15, 113(3), 303 - 8
Use of collagen shields containing amphotericin B in the treatment of experimental Candida albicans-induced keratomycosis in rabbits; Pleyer U et al.; We evaluated the effect of collagen shields presoaked with amphotericin B on the treatment of experimental Candida albicans-induced keratitis . Treatment results were compared to those of amphotericin B eyedrops instilled hourly . Forty-eight albino rabbits received intrastromal injections of 10(8) C . albicans organisms . Twenty-four hours later, eyes were treated for eight hours each day with hourly instillation of 0.15% amphotericin B drops, hourly instillation of saline drops, or application of a collagen shield presoaked in 0.5% amphotericin B for one hour . The rabbits were killed after one, three, or five days of treatment . Quantitation of fungi in the cornea was achieved by culturing homogenates and counting colony-forming units . Treatment with amphotericin B applied either as hourly instilled drops or absorbed in collagen shields significantly (P less than .05) reduced corneal fungal counts at all time points when compared to saline-treated control eyes . Rabbit eyes treated with amphotericin B-soaked collagen shields had significantly lower fungal counts compared with hourly instilled amphotericin B drops at Days 1 (P = .02) and 3 (P = .04), but not at Day 5 . The collagen shields were as effective in reducing the number of colony-forming units as were amphotericin B drops at Day 5 . These data suggest that collagen shields soaked in amphotericin B could be a useful and convenient treatment device in keratomycosis such as that caused by C . albicans.

Microvasc Res, 1992 Mar, 43(2), 218 - 26
Candida albicans adherence to endothelial cells; Mayer CL et al.; Mechanisms of adherence to vascular endothelial cells by microorganisms on a molecular level can be elucidated by using monoclonal antibodies, purified cell wall constituents, and receptor analogues . Since these agents are expensive and available in limited quantities, a microsystem for probing adherence mechanisms to these cells has become essential . We studied techniques to accurately quantify the adherence of L-{35S}methionine-labeled Candida albicans to human umbilical vein endothelial cells in a 96-well microtiter plate system while avoiding specific problems related to Candida coadherence and avid binding to plastic . The endothelial cells were grown on a collagen matrix in individually detachable microwells enabling the determination of the number of adherent organisms from radioactive counts of the entire well . This procedure has the critically important advantage of obviating the need to remove adherent Candida from the wells . Expressing adherence to endothelial cell monolayers as the percentage of total organisms added to each well significantly decreases the variability of the assay.

Kansenshogaku Zasshi, 1992 Mar, 66(3), 367 - 75
{Evaluation of serological and biochemical diagnosis of candidemia}; Inagaki M; In order to compare 4 serological and biochemical diagnostic tests, HA-test (Candida-HA-test), Cand-Tec, D-arabinitol detective test and Fungal Index (F.I.) were carried out in a total of 8 patients with candidemia, 6 were diagnosed to have systemic candidosis and 2 transient fungemia due to colonized catheters . Rabbits were given venous injections of 1.0 x 10(6) CFU (1 ml) of living Candida albicans type A to study the 4 diagnostic methods by sequential blood culture . Prior to clinical administration of antimycotics the diagnostic methods produced almost the same positive ratios . After administration of antimycotics, the HA-test became positive later than Cand-Tec or D-arabinitol because it detected antibodies in the serum, but its conversion to negative also tended to be slightly slower . Accordingly, the HA-test is considered to be useful for retrospective diagnosis of systemic candidosis . In Cand-Tec, D-arabinitol and F.I., the cases where reversion to normal was not achieved soon after therapy were intractable . In one case, the antigen values after therapy were four times as high as prior to treatment . To differentiate the two cases with transient fungemia from those with systemic candidosis HA- and D-arabinitol tests were considered to be superior to Cand-Tec and F.I . In the experiments with rabbits Cand-Tec was, in spite of its being positive in blood culture, always negative.

Antimicrob Agents Chemother, 1992 Mar, 36(3), 643 - 6
Effects of immunoglobulin G and low-dose amphotericin B on Candida albicans infections in burned mice; Neely AN et al.; Candidiasis causes serious problems for compromised hosts . Effective treatments for Candida albicans infections are few . To see if immunoglobulin (Ig) therapy could be beneficial, burn-immunocompromised mice were treated intravenously with 2.5 mg of five different IgG preparations 48 h postburn and post-C . albicans challenge . Despite up to fourfold differences in titer (1:1,600 to 1:6,400) to C . albicans, all preparations improved 10-day survival about 30% (P less than 0.0001) . Treatment with a low dose of amphotericin B (AmB; 0.09 mg/kg of body weight) intravenously 24 and 48 h after burn and challenge improved survival 9 to 45% (P less than 0.0001) . Treatment with a low dose of AmB plus IgG showed the same results as treatment with AmB alone and better results than treatment with IgG alone . Quantitative renal cultures from burned mice treated with AmB plus one IgG preparation, Sandoglobulin, showed that C . albicans counts decreased in sham-treated mice from 7.21 +/- 0.15 log10 CFU/g (mean +/- standard error of the mean) to 5.31 +/- 0.34, which was significantly less than counts with AmB (6.11 +/- 0.35) or Sandoglobulin (6.39 +/- 0.18) treatment alone . We conclude that (i) by using decreases in mortality and in renal fungal load as end points, treatment with IgG preparations alone or with a low dose of AmB alone protected burn-immunocompromised mice from candidiasis; (ii) though AmB plus one IgG preparation significantly decreased renal fungal load, the combination did not significantly decrease mortality beyond that found with AmB alone; and (iii) survival data did not correlate with IgG titers to C . albicans.

Pharmazie, 1992 Mar, 47(3), 182 - 4
{Synthesis and antimicrobial activity of chlorobenzyl benzylidene imidazolidinedione derivatives and substituted thiazolidinediones}; Lima MC et al.; The synthesis of five chlorobenzyl benzylidene imidazolidinediones and four fluorobenzyl benzylidene thiazolidinediones is described . In order to investigate their antimicrobial activity they are evaluated against microorganism such as Candida albicans, Neurospora crassa, Staphylococcus aureus, Mycobacterium smegmatis and Escherichia coli.

Chem Pharm Bull (Tokyo), 1992 Mar, 40(3), 661 - 5
Triazole antifungals . V . Synthesis and antifungal activities of some amides related to 3-acylamino-2-aryl-1-triazolyl-2-butanol; Tanaka T et al.; Amides, 2 and 3 related to the potent antifungal triazole-amide 3-acylamino-2-aryl-1-triazolyl-butanol(1) were synthesized starting from the triazole-alcohol 6 . The antifungal activity of 2 and 3 against a mouse systemic Candida albicans infection was found to be less potent than that of 1.

J Gen Microbiol, 1992 Mar, 138 ( Pt 3), 627 - 33
Detection of intracellular forms of secretory aspartic proteinase in Candida albicans; Homma M et al.; The extracellular proteinase (EPR) of Candida albicans was induced in a medium containing bovine serum albumin as sole nitrogen source . There were two intracellular forms in cells induced to produce EPR, a 43 kDa protein (EPR) and a 45 kDa protein (cross-reacting material of EPR; CRM-EPR); these were detected by immunoblotting using anti-EPR antiserum . The 43 kDa protein (EPR) may be the same as the extracellular form judging by molecular mass, and the 45 kDa protein (CRM-EPR) may be a precursor form of EPR . Many dense granules were observed by electron microscopy near the plasma membrane of the mother cells in EPR-producing cells . Both the 43 and 45 kDa proteins were recovered in a membrane fraction and were solubilized by Triton X-100 . When the membrane fraction was further fractionated by sucrose density gradient centrifugation, the 43 and 45 kDa proteins were differentially fractionated . This suggests that they were located in different membrane-bound structures and is consistent with an assumption that the 45 kDa protein is a precursor for EPR.

J Gen Microbiol, 1992 Mar, 138 ( Pt 3), 461 - 6
Expansion of the Candida albicans cell envelope in different morphological forms of the fungus; Merson-Davies LA et al.; Modes of cell envelope expansion were monitored in developing cells of Candida albicans 73/055 to which polystyrene beads were attached . Eight different conditions of culture medium, pH and temperature were used to promote growth in a variety of morphological forms . The cells were observed microscopically during growth in Sykes-Moore perfusion chambers, and sequential measurements of distances between the bead and the parent cell, and the bead and the apical tip were used to distinguish apical envelope expansion from general envelope expansion . Morphology index (Mi) was determined at each time point as an estimate of each cell's morphology . Calculations based on the measurements showed that general envelope expansion was inversely proportional to Mi, but that general expansion greater than 20% occurred only in cells with a final Mi less than 2.0, indicating that regulation of apical and general envelope expansion alone may be insufficient to determine the different morphologies seen in cells with higher Mi . The rate of expansion of the perimeter of cells was linearly proportional to the final Mi . This observation suggests that commitment to morphological development in C . albicans may in part involve commitment to a rate of envelope expansion, which itself helps determine the final morphology of a cell.

Arch Oral Biol, 1992 Mar, 37(3), 237 - 9
The effect of storage in liquid nitrogen on the isolation of oral yeasts in human saliva; Brambilla E et al.; Stimulated whole saliva samples were collected from a group of 127 6-yr-old schoolchildren . Each sample was divided into three parts . The first two, one of which contained added glycerol, were immediately frozen in liquid nitrogen and stored at -196 degrees C for 2 months . The third part was transferred to the laboratory and plated on selective medium for yeasts . Colony counts of the frozen and non-frozen samples were then compared . Statistical analysis showed a highly significant correlation between the counts for frozen and unfrozen samples . A high (40.1%) prevalence of yeast carriers was found, and Candida albicans was the most frequently recovered yeast.

J Am Acad Dermatol, 1992 Mar, 26(3 Pt 2), 408 - 10
Prevalence of dermatophytosis in patients with diabetes; Lugo-Somolinos A et al.; BACKGROUND: Controversy still exists as to whether dermatophytic skin infection is truly more common in patients with diabetes . OBJECTIVE: The purpose of this study was to determine the true prevalence of dermatophytosis in diabetic patients as compared with a control population . METHODS: One hundred consecutive diabetic patients were examined for evidence of fungal disease of the skin and compared with nondiabetic, nonimmunocompromised patients . Potassium hydroxide preparation and fungal cultures were obtained from all suspect lesions . RESULTS: Thirty-one percent of the diabetic population had culture-proven fungal infections compared with 33% of the control group . The organism most commonly isolated was Trichophyton rubrum in both groups, and the feet were the most common site of infection . Candida albicans was more prevalent in the control group, affecting the nails in particular (24% vs 15% in the diabetic patients) . CONCLUSION: This study shows that there does not seem to be an increased prevalence of dermatophytosis in diabetic patients as compared with a control, nondiabetic patient.

J Clin Pharmacol, 1992 Mar, 32(3), 248 - 55
Evolving pathogens in vulvovaginal candidiasis: implications for patient care; Horowitz BJ et al.; Over the past two decades, an increasing trend in the number of vaginal infections attributable to yeasts other than Candida albicans has emerged . Of these non-albicans species, C . tropicalis and C . glabrata appear to be the most important . The change in incidence pattern of yeast vaginitis can be expected to impact greatly on the treatment of this condition, because many currently used drug therapies (e.g., imidazoles) for C . albicans vaginitis do not adequately eradicate non-albicans species . A possible explanation for the recent increased selection of these species may be the shortened antifungal therapies that have been introduced during the past decade . These 1- to 3-day regimens with the older imidazoles may suppress C . albicans, but create an imbalance of flora that facilitate an overgrowth of non-albicans species . The recognition of yeast speciation and the need for use of a broad-spectrum antifungal preparation that covers these organisms is now apparent.

Curr Genet, 1992 Mar, 21(3), 203 - 6
Direct selection of galactokinase-negative mutants of Candida albicans using 2-deoxy-galactose; Gorman JA et al.; The galactose analogue 2-deoxy-galactose (2DG) has been widely used to select for mutations in the gene encoding the galactose pathway enzyme galactokinase (GalK) . We have tested the effect of 2DG on Candida albicans to see if it could be used to obtain GalK- mutants in this diploid asexual yeast . 2DG was shown to be toxic to wild-type cells . Enzyme assays demonstrated that 2DG can induce GalK as efficiently as galactose . Examination of the initial rate of galactose uptake indicated that the galactose transport system is constitutive . 2DG-resistant mutants were isolated from mutagenized cultures and shown to have very low levels of GalK activity . The potential genetic applications of this system of direct mutant selection are discussed.

Am J Obstet Gynecol, 1992 Mar, 166(3), 887 - 90
Cellular immunity of patients with recurrent or refractory vulvovaginal moniliasis; Fong IW et al.; Cellular immunity was studied in 73 patients with recurrent vaginal moniliasis and 37 healthy controls, by skin testing with the multitest CMI kit and Candida antigen, with measurement of lymphoblastic transformation to phytohemagglutinin, antigens of Candida albicans, mumps, and streptokinase . Eighteen patients (24.7%) had a hypoergic or anergic response to Candida antigen on skin testing versus two controls (5.4%), p = 0.01 . Overall, the patient's lymphoblastic proliferation to mitogen and various antigens was not significantly different from that of the controls . However, a subgroup of younger women (19 to 29 years old) had impaired responses to Candida antigen when compared with age-matched controls, 58% versus 17%, p less than 0.005 . Most women with current vaginal moniliasis had normal cellular immunity.

Infect Immun, 1992 Mar, 60(3), 876 - 84
Gene isolation by complementation in Candida albicans and applications to physical and genetic mapping; Goshorn AK et al.; We have isolated three genes, ARG57, SER57, and LYS1, on the basis of their function in Candida albicans . A C . albicans transformation vector containing the C . albicans URA3 gene, a Candida ARS sequence, and a portion of the Saccharomyces cerevisiae 2 microns circle containing the replication origin was constructed . Clones from genomic libraries in this vector were isolated by direct complementation of the auxotrophies in strain 1006 (arg57 ser57 lys1 ura3 MPA1) . Transformants typically contain two to four plasmids in a mixed tandem multimer . A scheme to resolve mixed multimers into monomers in vivo by transformation of S . cerevisiae with Candida transformant DNA selecting Ura+ transformants was devised . Monomeric plasmids were then isolated by transformation of Escherichia coli with the S . cerevisiae transformant DNA . These were retested by transformation of strain 1006 to identify the specific plasmid that complemented the auxotrophy . The chromosomal locations of the genes were determined by hybridization to C . albicans chromosomes separated on contour-clamped homogenous electric field gels . We used these locations to assess the stability of individual C . albicans chromosomes in parasexual genetic analysis . The Lys(+)-complementing clone was shown to be LYS1 by complementation of S . cerevisiae lys1 mutants . These cloned genes help to align the Candida physical and genetic maps and provide additional markers for the transformation system.

Infect Immun, 1992 Mar, 60(3), 853 - 63
Growth inhibition of Candida albicans by interleukin-2-activated splenocytes; Beno DW et al.; Murine splenocytes, Percoll-enriched low-density lymphocytes, and interleukin-2 (IL-2)-activated lymphocytes were assessed for the capacity to limit the growth of the hyphal form of Candida albicans . No fungal-growth-inhibitory activity was exhibited for C . albicans by either splenocytes or Percoll-enriched lymphocytes . These cells were capable of cytotoxic activity for a natural killer cell-sensitive cell line . However, when cultured for several days with IL-2, splenocytes acquired the capacity to inhibit the growth of the fungus . The appearance of the antifungal activity coincided with the development of cytotoxic activity for the natural killer cell-insensitive cell line . Anti-C . albicans and antitumor activities of IL-2-activated lymphocytes were competitively and reciprocally inhibited by C . albicans and the natural killer cell-sensitive and -insensitive cell lines . The antifungal activity of the IL-2-activated lymphocytes was exhibited against a number of clinical isolates of C . albicans and related fungal species . IL-2-activated human peripheral blood lymphocytes also acquired the capacity to inhibit the growth of C . albicans . These data show that in vitro growth inhibition can be mediated by IL-2-stimulated lymphocytes which are neither fungal strain nor mammalian species restricted in their biological activity.

Infect Immun, 1992 Mar, 60(3), 832 - 7
Early differential molecular response of a macrophage cell line to yeast and hyphal forms of Candida albicans; Blasi E et al.; The dimorphic transition of Candida albicans from the yeast (Y-Candida) to the hyphal (H-Candida) form is a complex event; the relevance of this transition in fungal pathogenicity is still poorly understood . By using a cloned macrophage cell line (ANA-1), we questioned whether the interaction between macrophages and Y-Candida or H-Candida could affect specific cell functions, i.e., tumor necrosis factor and lysozyme production . We found that ANA-1 macrophages selectively responded to H-Candida with increased tumor necrosis factor and downregulated lysozyme, as assessed by measurement of relative mRNA levels and secreted biological activities . The H-Candida-mediated effects were (i) dependent upon the ratio between ANA-1 macrophages and H-Candida, (ii) detectable after 1 h of coincubation, and (iii) accomplished without fungal ingestion . Conversely, Y-Candida, which was found inside the ANA-1 macrophages, did not affect tumor necrosis factor and lysozyme production, nor did it prevent the macrophage response to other stimuli . Overall, these results indicate that a macrophage can distinguish between Y-Candida and H-Candida and that only the latter is able to modulate specific functions . H-Candida is recognized and probably processed as an extracellular target . The possible implication of macrophages as autocrine and paracrine regulatory cells during Candida infections is discussed.

Infect Immun, 1992 Mar, 60(3), 1041 - 6
Effect of lectins on hepatic clearance and killing of Candida albicans by the isolated perfused mouse liver; Sawyer RT et al.; The isolated perfused mouse liver model was used to study the effects of various lectins on hepatic trapping and killing of Candida albicans . After mouse livers were washed with 20 to 30 ml of perfusion buffer, 10(6) C . albicans CFU were infused into the livers . At the time of recovery, 63% +/- 2% (mean +/- standard error of the mean) of the infused C . albicans CFU were recovered from the liver and 14% +/- 1% were recovered from the effluent for a total recovery of 77% +/- 2% . This indicated that 86% +/- 9% of the original inoculum was trapped by the liver and that 23% +/- 2% was killed within the liver . When included in both preperfusion and postperfusion buffers (0.2 mg of lectin per ml), Ulex europeaus lectin (binding specificity for fucose) decreased hepatic trapping of C . albicans by 37% and eluted trapped C . albicans from the liver only when included in postperfusion buffer . By comparison, treatment of C . albicans with U . europeaus lectin before infusion had no effect on the trapping or killing of yeast cells . When Lens culinaris lectin (binding specificity for mannose) was included in the perfusion buffers, hepatic killing of C . albicans increased by 16% with no significant effect on hepatic killing when yeast cells were treated with L . culinaris lectin before infusion . Forty to 55% of the infused C . albicans were killed when concanavalin A (binding specificities for mannose and glucose), Glycine max (binding specificity for N-acetylgalactosamine), or Arachis hypogea (binding specificity for galactose) lectin was included in the perfusion buffer or when yeast cells were treated with these lectins before their infusion . When C . albicans was treated with concanavalin A at a concentration of less than 0.02 mg/ml, hepatic killing of yeast cells was not significantly increased . The data suggest that a fucose-containing receptor on the surface of either sinusoidal endothelial cells or Kupffer cells is involved in the trapping of C . albicans by the perfused mouse liver . Moreover, lectins with binding specificities for mannose, N-acetylgalactosamine, and galactose increased hepatic killing of C . albicans.

Mycoses, 1992 Mar-Apr, 35(3-4), 89 - 94
The lectin type of Candida albicans--an epidemiological marker relevant to pathogenesis; Korting HC et al.; Fifty Candida albicans strains isolated from the oral cavities of HIV-infected patients were typed with 14 different lectins by means of agglutination reactions . Sixteen different lectin types could be distinguished, the most frequent type representing 22% of strains . A change in the lectin type was found in about half of the Candida albicans strains representing control cultures from identical individuals . A simplified typing scheme based on three lectins seems to be almost as efficacious for epidemiological application.

Mycoses, 1992 Mar-Apr, 35(3-4), 83 - 8
A modified method for experimental candidosis in mice avoiding lethality; Hanel H et al.; A model is presented which selected one out of 150 Candida albicans strains for the evaluation of antifungal agents . The mice were inoculated with 6 x 10(5) CFU of strain 352 into the tail vein . The strain has a moderate phospholipase B (PLB) activity in vitro and was originally isolated from a stool sample from a patient in an intensive care unit . This infection leads to very little suffering in the infected animals during the 6-day observation period . Kidney counts at day 5 after infection can give a first indication for a possible fungistatic mechanism . Possible interesting drugs can then be evaluated by a second set of experiments using a longer observation time to investigate the compounds for fungicidal properties . The model suggests that screening for systemic antifungals by avoiding lethality of mice in the first place can be done.

Zhonghua Fu Chan Ke Za Zhi, 1992 Mar, 27(2), 93 - 5, 124-5
{Relation between macrophages in peritoneal fluid of endometriosis and infertility}; Cao SJ; Peritoneal fluid was collected from 18 endometriosis-associated infertile patients and 14 unexplained infertile women . The cells were counted in a hemacytometer and subjected to morphologic analysis . The phagocytic activity on Candida Albicans and on Sperms was evaluated and the activity of acid phosphatase in the pelvic fluid and within the macrophages were measured . The results showed that the endometriosis samples have macrophages of large size as compared with the macrophages found in unexplained infertile or fertile women, the concentration of pelvic macrophages in endometriosis is higher, the phagocytic and bactericidal activity is also higher and the macrophages in endometriosis engulf sperms as well . The accentuated activity of pelvic macrophages may be associated with the infertility in patients with endometriosis.

J Leukoc Biol, 1992 Mar, 51(3), 305 - 6
Differential effects of CD4+ and CD8+ cells in acute, systemic murine candidosis; Coker LA 3rd et al.; Monoclonal antibody (mAb) depletion was used to assess contributions of CD4+ and CD8+ cells in resistance to systemic murine Candida albicans infection . Depletion of CD8+ cells did not influence either survival or mean survival time (MST); however, depletion of CD4+ cells significantly enhanced both survival and MST . Combined depletion of both CD4+ and CD8+ cells significantly lengthened the MST but did not enhance survival . A protective influence of CD8+ cells could be deduced but, to be manifested, required depletion of an overshadowing immunopathologic CD4+ response.

Antimicrob Agents Chemother, 1992 Feb, 36(2), 498 - 501
In vitro and in vivo activities of SCH 42427, the active enantiomer of the antifungal agent SCH 39304; Loebenberg D et al.; SCH 39304, a new triazole antifungal agent, is a 50:50 racemic mixture of two enantiomers, SCH 42427 and SCH 42426 . The activities of these three compounds were compared in a series of in vitro and in vivo experiments . SCH 42427 was twofold more active in vitro against a variety of yeasts and dermatophytes than SCH 39304, while SCH 42426 was inactive (MICs greater than 64 micrograms/ml) . In a systemic Candida albicans infection in mice, SCH 42427 administered orally (p.o.) (50% protective dose {PD50}, 0.17 mg/kg of body weight; 50% effective dose, {ED50}, 0.47 mg/kg) had greater efficacy than SCH 39304 (PD50, 0.21 mg/kg; ED50, 0.62 mg/kg) and SCH 42426 (greater than 100 mg/kg for PD50 and ED50) . In a pulmonary Aspergillus flavus infection in mice, SCH 42427 p.o . (PD50, 13 mg/kg) was also more effective than SCH 39304 (18 mg/kg) and SCH 42426 (greater than 250 mg/kg) . In a C . albicans vaginal infection in hamsters, SCH 42427 p.o . (ED50, 3.5 mg/kg) was more active than SCH 39304 (8.5 mg/kg) and SCH 42426 (320 mg/kg) . Following topical administration, against a Trichophyton mentagrophytes infection in guinea pigs, SCH 42427 was about 2-fold more active than SCH 39304 and about 100-fold more active than SCH 42426 . These and other results indicated that SCH 42427 is the active enantiomer, responsible for all the antifungal activity observed with SCH 39304.

Am J Gastroenterol, 1992 Feb, 87(2), 224 - 9
Gastrointestinal hemorrhage due to gastrointestinal Mycobacterium avium intracellulare or esophageal candidiasis in patients with the acquired immunodeficiency syndrome; Cappell MS et al.; A 33-yr-old black intravenous drug abuser with the acquired immunodeficiency syndrome (AIDS) had a massive fatal upper gastrointestinal hemorrhage due to profound and diffuse esophageal ulceration from Candida, as demonstrated by postmortem examination . A 2-yr-old white male with congenitally acquired AIDS had a massive fatal esophageal bleed as a result of esophagitis from Candida albicans, as proven by pathologic examination and culture of endoscopic biopsies . A 27-yr-old black human immunodeficiency virus-seropositive female died from massive lower gastrointestinal bleeding due to extensive small and large intestinal ulceration caused by Mycobacterium avium intracellulare, as proven by microscopic examination and mycobacterial culture of intestinal tissue . These reports extend the clinical spectrum of these infections in AIDS patients by demonstrating that these infections can produce gastrointestinal bleeding.

Cell Immunol, 1992 Feb, 139(2), 438 - 54
In vivo modulation of lymphokine-activated killer cell activity by cell wall components of Candida albicans; Scaringi L et al.; We have previously reported that inoculating CD2F1 mice intraperitoneally with five doses of 2 x 10(7) inactivated Candida albicans (CA) cells was associated with the induction of lymphokine-activated killer (LAK)-like effectors . In this study we investigated the ability of some purified cell wall components of CA (CA-CW) to induce LAK-like cells in vivo . Multiple administrations of glucan ghost (GG), a mannoprotein mixture (MP) and a low-protein mannan fraction (M) at variance with whole CA did not induce LAK-like cells in the peritoneal cavity . However, the broad-spectrum antitumor cytotoxicity induced by CA could be recalled to a high level by a booster dose of MP and M, but not GG, given up to 70 days after the multiple CA-treatment . This induced cytotoxicity was maximum when the booster was given on Day +14 after CA-treatment and minimum on Day +70 . In CA-treated mice, inoculated on Day +30 with CA or MP, LAK-like cytotoxicity was already significantly increased 4 hr after the booster, but the maximum value was reached at 24 hr . Anti-mannan antibodies did not interfere with LAK-like cells induction by CA because splenectomy before CA-treatment or passive administration of anti-mannan antibodies had no effect on the rapid activation of cytotoxicity by CA or a booster dose of MP . Administration of recombinant human interleukin-2 (rhIL-2) to CA-treated mice induced a higher level of NK activity than that induced by the same dose in untreated control mice, but did not activate LAK-like effectors . The results indicate that LAK-like effectors are easily generated in the peritoneal cavity by a booster with a defined antigenic constituent of CA cell wall for a long period in CA-sensitized mice.

J Infect Dis, 1992 Feb, 165(2), 389 - 92
Prevalence of esophageal Candida colonization in a Danish population: special reference to esophageal symptoms, benign esophageal disorders, and pulmonary disease; Andersen LI et al.; A population sample selected at random after stratification for the presence of pulmonary disease was screened for benign esophageal disease; 175 subjects agreed to participate in the invasive investigation, 86 without pulmonary disease and 89 with chronic obstructive pulmonary disease (COPD) . Of these, 169 underwent endoscopy of the upper gastrointestinal tract, 164 had mucosal brushings for the presence of Candida albicans in the esophagus, 169 had esophageal pressure measurements, and 113 had 12-h pH measurements . One hundred fourteen subjects with benign esophageal disease were found . The prevalence of C . albicans in the esophagus (greater than or equal to 50 colonies) in subjects with and without COPD was 12.3% and 25.1%, respectively . C . albicans occurred equally in subjects with and without esophageal symptoms . There was no relation between the presence of C . albicans and benign esophageal disease and no significant clinical correlation between esophageal plaques and colony counts of C . albicans.

Arzneimittelforschung, 1992 Feb, 42(2), 160 - 3
Syntheses and antifungal activities of some 3-(2-phenylethyl)-5-substituted- tetrahydro-2H-1,3,5-thiadiazine-2-thiones; Ertan M et al.; Ten new 3-(2-phenethyl)-5-substituted-tetrahydro-2H-1,3,5-thiadiazine-2- thiones were synthesized by the reaction of phenylethylamine with carbon disulfide and potassium hydroxide, followed by formaldehyde and appropriate amino acids . The structures of these compounds have been confirmed by UV, IR, 1H-NMR and elementary analysis . The antifungal activities of the compounds were tested by tube dilution method against yeast-like fungi (Candida albicans, C . parapsilosis, C . stellatoidea and C . pseudotropicalis) and minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) values were determined . All compounds proved to be highly effective against yeast-like fungi (MFC range: 1.56-12.5 micrograms/ml).

Antimicrob Agents Chemother, 1992 Feb, 36(2), 262 - 6
Influence of phospholipid/amphotericin B ratio and phospholipid type on in vitro renal cell toxicities and fungicidal activities of lipid-associated amphotericin B formulations; Joly V et al.; We studied the influence of the lipid/amphotericin B (AMB) ratio and the phospholipid type on the in vitro renal cell toxicity and antifungal efficacy of lipid-associated AMB (L-AMB) . L-AMB was prepared at one of two different lipid/AMB ratios (1 and 40) by incubating AMB with empty small unilamellar vesicles, made from one of three different phospholipids: dipalmitoyl-, dimirystoyl-, and distearoylphosphatidylcholine (DPPC, DMPC, and DSPC, respectively) . Renal cell toxicity, investigated through an assessment of the Na-dependent uptake of phosphate by proximal tubular cells, and fungicidal effect against Candida albicans were studied after 1 h of treatment at 37 degrees C . The amount of unbound AMB present in each L-AMB formulation was studied by use of circular dichroism . At a lipid/AMB ratio of 40, the three lipidic formulations were not toxic for renal cells but were less effective against C . albicans than AMB; however, DSPC-AMB, which contained 50% unbound AMB, was more effective against C . albicans than DPCC-AMB or DMPC-AMB, containing 0 and 13% unbound AMB, respectively . At a lipid/AMB ratio of 1, the antifungal effects of L-AMB and AMB were similar, whatever the phospholipid used, but only DMPC-AMB remained highly protective against AMB renal cell toxicity, despite the presence of the same amount of unbound AMB (50%) in DMPC-AMB and DPPC-AMB . We conclude that the in vitro activities and renal cell toxicities of different L-AMB formulations are influenced by the phospholipid type and the lipid/AMB ratio . The optimal ratio depends on the phospholipid itself . At a lipid/AMB ratio of 40, the antifungal activity depends mainly on the amount of unbound AMB in the formulation . At a lipid/AMB ratio of 1, the renal cell toxicity also depends on the fluidity of the phospholipid.

Arch Fr Pediatr, 1992 Feb, 49(2), 113 - 5
{Isolated Candida albicans meningitis after treatment of B lymphoma}; Damay M et al.; A case of candida meningitis occurring in a child treated for a lymphoma is reported . Diagnosis was made with Candida albicans culture in the CSF . Blood cultures were negative . Cerebral CT scan was normal . No other localization was found . The child was successfully treated by amphotericin B (initially with 5-fluorocytosin) . Fluconazole was continued orally later on . This case is noteworthy by the absence of other localization, the favourable evolution and its occurrence in childhood . The therapeutic attitude and prevention are discussed.

Rev Clin Esp, 1992 Feb, 190(2), 79 - 81
{Sclerosing cholangitis and AIDS}; Ramos C et al.; Bile tract pathology in AIDS has been described as an incomplete biliary obstructive syndrome and acalculous cholecystitis . Most reported cases have been associated to bile ducts infection by Cytomegalovirus (CMV) and/or Cryptosporidium . We present a case of sclerosing cholangitis and acalculous cholecystitis in an AIDS patient in whom Cryptosporidium was identified in the cholecystectomy sample and this same agent together with Candida Albicans in bile . We highlight the need to suspect this pathology in HIV infected patients who present a bile obstruction picture and/or cholecystitis, the possible etiological role of Candida Albicans, which has not been previously described, as well as the increasing association of bile pathology and AIDS.

Mol Microbiol, 1992 Feb, 6(4), 497 - 502
Expression of chitin synthase genes during yeast and hyphal growth phases of Candida albicans; Chen-Wu JL et al.; Chitin, the beta 1,4-linked polymer of N-acetylglucosamine, is a fibrous polysaccharide that in many yeasts helps to maintain the structure of the mother-bud junction and in filamentous fungi is often the major supporting component of the cell wall . We have previously described a Candida albicans chitin synthase, CHS1 . The DNA and derived protein sequences of a second gene, CHS2, are presented and compared with previously published gene sequences . Northern blot analysis shows that strikingly different levels of synthase 1 and 2 expression occur during yeast and hyphal phases of Candida growth.

Biochem Int, 1992 Feb, 26(2), 317 - 25
Degradation of indulin by Candida albicans; Vasudevan N et al.; Candida albicans utilized 14C (ring) labelled dehydropolymer of coniferyl alcohol, 14C-teakwood lignin and indulin and released p-hydroxybenzoic acid, vanillic acid, 3,4-dihydroxybenzoic acid and catechol as by products from lignin . Candida albicans produced catechol 1,2-dioxygenase, protocatechuate 3,4-dioxygenase, intra- and extracellular polyphenol oxidase and peroxidase during indulin degradation . The study suggests that Candida albicans degrades different types of lignin.

J Antibiot (Tokyo), 1992 Feb, 45(2), 160 - 70
A new series of natural antifungals that inhibit P450 lanosterol C-14 demethylase . II . Mode of action; Aoki Y et al.; From a Penicillium sp . we identified a new series of antifungals having a tetrahydropyran skeleton with an alkenyl side chain . We elucidated the mode of action of Ro 09-1470, the most active compound of the series . Treatment of Candida albicans with the compound caused an accumulation of C-14 methyl intermediates of ergosterol at concentrations of which no significant interference with the biosyntheses of other macromolecules and respiration was observed . P450 lanosterol C-14 demethylase (P450(14DM)) activity was inhibited and furthermore, the binding of Ro 09-1470 to the heme of the enzyme was demonstrated by a difference spectrum . We conclude that Ro 09-1470 is the first natural antifungal that inhibits the P450(14DM) of fungi.

Clin Infect Dis, 1992 Feb, 14(2), 422 - 6
Fluconazole treatment of catheter-related right-sided endocarditis caused by Candida albicans and associated with endophthalmitis and folliculitis; Venditti M et al.; An unusual case of catheter-related right-sided endocarditis, endophthalmitis, and extensive folliculitis, apparently caused by a single DNA biotype of Candida albicans, was successfully treated with a 6-month course of fluconazole plus two intravitreous doses of amphotericin B . The patient was a 21-year-old man who underwent colectomy for diffuse polyposis and developed the clinical syndrome just described following total parenteral nutrition for the treatment of purulent anal fistulas . Fluconazole was initially administered at a daily dose of 200 mg, with 600 mg daily given after 4 weeks . Clinical improvement resulted, with no relapse during 14 months of follow-up . Sequential measurements by an enzyme-linked immunosorbent inhibition assay demonstrated that levels of circulating mannoprotein antigen of C . albicans fell from 75 ng/mL to less than 1 ng/mL after the institution of fluconazole therapy . These observations seem to confirm previous reports on the efficacy of fluconazole as sole therapy for candidal endocarditis and suggest a role for serological studies in clinical monitoring of severe candidal infections.

Br J Haematol, 1992 Feb, 80(2), 137 - 43
Activation of human eosinophil and neutrophil functions by haematopoietic growth factors: comparisons of IL-1, IL-3, IL-5 and GM-CSF; Fabian I et al.; We compared the effect of haematopoietic growth factors granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-1, IL-3, and IL-5 on the functional activation of human eosinophils and neutrophils from the same donor . All four colony-stimulating factors (CSF) enhanced the phagocytosis of Candida albicans by eosinophils and increased staphylococcal, but not Candida, killing . GM-CSF and IL-5 had a profound stimulating effect on eosinophil staphylocidal activity . GM-CSF and IL-3 enhanced the generation of leukotriene C4 (LTC4) induced by calcium ionophore A23187 and the release of arylsulphatase and beta-glucuronidase from specific and small granules of eosinophils . In contrast, IL-1 and IL-5 had no effect on degranulation . GM-CSF and IL-1 enhanced phagocytosis of C . albicans by neutrophils, and GM-CSF stimulated degranulation and the release of the enzymes beta-glucuronidase and arylsulphatase from neutrophils while IL-1 stimulated the release of arylsulphatase only . This study indicates that the eosinophil-active colony-stimulating factors can markedly enhance the host defence function of the eosinophil and even make it the equal of the neutrophil in staphylocidal activity . The CSF-activated eosinophil, however, may cause inappropriate inflammation and normal tissue damage.

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