Candida albicans

J Prosthet Dent, 1990 Dec, 64(6), 691 - 4
Effects of crude drugs and berberine hydrochloride on the activities of fungi; Nakamoto K et al.; The effects of crude drugs on fungi have been used for a thousand years in China and Japan . These drugs include: Saussureae radix, Magnoliae cortex, Cinnamomi cortex, Hydrangeae dulcis folium, and Artemisiae capillarius flos . The activity of Coptidis rhizoma and Phellodendri cortex was stronger than other crude drugs against the three fungi . Berberine hydrochloride, which is a component of the two crude drugs, was investigated . Minimal inhibitory concentration values of berberine hydrochloride were 1, 0.125, and 0.5 mg/ml against Candida albicans, C . tropicalis, and C . glabrata, respectively . In C . glabrata, compared with C . albicans and C . tropicalis, berberine hydrochloride greatly inhibited the growth of fungi.

J Gen Microbiol, 1990 Dec, 136 ( Pt 12), 2433 - 42
Variation in the electrophoretic karyotype analysed by the assignment of DNA probes in Candida albicans; Iwaguchi S et al.; By using pulsed-field gel electrophoresis, we have separated the entire chromosome bands and examined the electrophoretic karyotypes of 27 strains of Candida albicans . The electrophoretic karyotype varied widely among these strains . Their chromosomal DNAs were resolved into 7-12 bands ranging in size from 0.42 to 3.0 Mb . Most of the separated chromosomal bands were assigned by eight cloned C . albicans DNA probes . These results suggest that the haploid number of C . albicans chromosomes is eight . Each of the probes hybridized specifically to one or two bands of similar size in most strains . With the exception of the MGL1 probe, when two bands were detected by one probe, the size of one of them was very conserved whilst the other was of fairly variable size . The sizes of the chromosome bands assigned by the MGL1 probe were much more variable . As C . albicans is considered to be a diploid organism, it is inferred that the karyotype polymorphism between strains is mainly derived from wide size heterogeneity in one of the homologous chromosomes . Furthermore, we have confirmed species-specific and strain-specific variation in medically important Candida species (C . stellatoidea, C . tropicalis, C . parapsilosis, C . krusei, C . guilliermondii, C . kefyr and C . glabrata) . Electrophoretic karyotype analysis is thus useful for species assignation . The TUB2 probe, encoding C . albicans beta-tubulin, hybridized to the chromosomal DNA of all the Candida species examined, but four C . albicans probes exhibited cross-species hybridization with C . stellatoidea only . The karyotype of C . stellatoidea seems to be within the range of the intraspecies variation observed in C . albicans.

J Gen Microbiol, 1990 Dec, 136 ( Pt 12), 2421 - 32
Wall mannoproteins in cells from colonial phenotypic variants of Candida albicans; Martinez JP et al.; Candida albicans ATCC 26555 switched at high frequency (10(-1) to 10(-3)) between several phenotypes identified by colony morphology on a defined mineral amino-acid-containing agar medium supplemented with arginine and zinc (LAZ medium) . When cells taken from colonies exhibiting distinct morphologies were plated directly onto LAZ agar, spontaneous conversion to all the variant phenotypes occurred at combined frequencies of 2.1 x 10(-1) to 9.5 x 10(-3) . However, when cells taken from the different colonial phenotypes were plated directly onto an undefined medium (yeast extract/peptone/dextrose; YPD medium), or first incubated in liquid YPD medium and then cloned on YPD agar, all colonies observed exhibited the same phenotype (smooth-white) . When cells from the smooth-white colonies were plated as clones on LAZ agar, the original switch phenotype reappeared . These results suggest that environmental conditions such as the growth medium (and possibly the temperature) influence switching by suppressing phenotype expression, but have no effect on genotype . The variant colony morphologies also appeared to be associated with differences in the relative proportions of yeast and mycelial cells . Zymolyase digests of wall preparations obtained from cells belonging to different colonial phenotypes were analysed by SDS-PAGE . After blotting to nitrocellulose paper, the mannoproteins were stained with Concanavalin A, with a polyclonal antiserum enriched in antibodies against mycelium-specific wall components, and with a monoclonal antibody raised against a high-molecular-mass mannoprotein band (260 kDa) specific to the walls of mycelial cells . The results suggest that phenotypic switching might be associated with changes in the degree of glycosylation in high-molecular-mass mannoproteins, or in the way these mannoproteins are bound to other cell wall components.

Antimicrob Agents Chemother, 1990 Dec, 34(12), 2304 - 6
Effects of pentamidine alone and in combination with ketoconazole or itraconazole on the growth of Candida albicans; St-Germain G; The in vitro interaction of pentamidine with ketoconazole and with itraconazole was studied with 10 strains of Candida albicans isolated from acquired immunodeficiency syndrome patients and one azole-resistant strain . Although growth curves indicated that concentrations of 1 microgram or more of pentamidine per ml significantly inhibited the growth of C . albicans, MICs and minimum fungicidal concentrations (MFCs) were greater than or equal to 10 micrograms/ml . Combinations of ketoconazole and pentamidine did not appear to have any significant effect on MICs or MFCs with most strains . However, the azole-resistant strain exhibited a 2-log decrease in MIC when exposed to ketoconazole combined with 1.0 microgram or more of pentamidine per ml . Similar results were obtained with itraconazole . An Eagle, or paradoxical, effect was observed with four strains exposed to itraconazole alone and in combination with 0.01 and 0.1 microgram of pentamidine per ml . This effect was not seen when concentrations of pentamidine reached 1.0 microgram/ml . Although no fungicidal effect was observed with any of these drugs alone, itraconazole combined with 10 micrograms of pentamidine per ml was fungicidal for eight strains . No signs of antagonism between pentamidine and these two antifungal agents were observed.

Infect Immun, 1990 Nov, 58(11), 3765 - 9
Recognition of binding sites on Candida albicans by monoclonal antibodies to human leukocyte antigens; Mayer CL et al.; Candida albicans exhibits examples of human molecular mimicry, including receptors resembling human steroid receptors and human complement receptor (CR)-like receptors that bind the complement fragments C3d and iC3b . To further characterize the epitopes of the Candida human CR-like molecules, a panel of monoclonal antibodies (MAbs) against epitopes within the human CR3 was used . MAbs Mo1, M1/70HL, and 7C3 bound to the germ tube, as assessed by immunofluorescence . MAbs Leu15, 60.1, and 95G8 did not bind . Miscellaneous MAbs against other antigens on human leukocytes (B2, 3D9, and OKT4) did not bind . However, MY9, which recognizes a monocyte antigen, bound extensively to the germ tube . The binding of certain anti-CR3 MAbs suggested limited identity between the Candida CR3-like receptor and the human CR3 . The binding of MY9 identified an antigen recognized by a MAb to a human cell antigen not previously known to exist on C . albicans.

Mycopathologia, 1990 Nov, 112(2), 105 - 12
Efficacy of brain heart infusion-egg albumen agar, yeast extract phosphate agar and peptone glucose agar media for isolation of Blastomyces dermatitidis from sputum; Chaturvedi S et al.; The efficacy of brain heart infusion (BHI)-egg albumen agar, yeast extract phosphate agar and several modified peptone glucose agar media was evaluated for isolation of Blastomyces dermatitidis from sputum concomitantly seeded with the yeast form of the pathogen and Candida albicans . Based upon high per cent culture positivity of sputum, improved recovery (CFU/ml) of the seeded inoculum, faster growth rate of B . dermatitidis and low level of contamination, BHI-egg albumen agar, followed by yeast extract phosphate agar are recommended as the media of choice for the isolation of B . dermatitidis from contaminated clinical specimens.

Przegl Dermatol, 1990 Nov-Dec, 77(6), 399 - 404
{The usefulness of determining specific immunoglobulins E in atopic dermatitis in light of personal investigations}; Bajcar S; In 67 patients with allergic dermatitis the levels of total IgE and specific IgEs against 14 allergens were determined by the FAST-test method . The most frequently raised levels of specific IgE were found against the following allergens: dog epidermis, timothy grass, Candida albicans, beef . Test by FAST method confirmed increased levels of total and specific IgEs in most cases of atopic dermatitis.

Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi, 1990 Nov-Dec, 31(6), 396 - 401
{Congenital cutaneous candidiasis: report of two cases}; Chiou CB et al.; Congenital cutaneous candidiasis is a very rare disease . We reported two newborn infants in whom generalized skin eruption was noted at birth, characteristics of erythematous papules and pustules . The eruption involved head, face, neck, trunk and extremities . Candida albicans was demonstrated on direct KOH smear, by surface fungal cultures and skin biopsy . The disease implies a congenital intrauterine infection and is different from neonatal candidiasis which manifests as thrush, diaper dermatitis . The route of infection is ascending in congenital cutaneous candidiasis . The skin eruption is usually noted at birth or within 12 hours after delivery as a diffuse erythematous maculopapula, with pustules or vesicles distributed over head, face, neck, trunk and extremities . There is no fever; other constitutional signs are lacking . No evidence of impaired immunological responsiveness has been noted in previous study . Clinical features, direct smear examination of specimen and appropriate cultures are useful in differentiating the lesions from other more common dermatoses of the neonatal period . Topical antifungal therapy is sufficient unless systemic candidiasis is present . Prognosis for congenital cutaneous candidiasis is good.

J Appl Bacteriol, 1990 Nov, 69(5), 692 - 6
A comparison of the sterol content of multiple isolates of the Candida albicans Darlington strain with other clinically azole-sensitive and -resistant strains; Howell SA et al.; The mechanism of azole resistance of Candida albicans NCPF 3310 (the deposited culture of the Darlington strain) has been investigated but never fully explained . Seven isolates of this strain, from various sources, were examined by gas chromatography-mass spectrometry to detect changes in the sterol composition following passage through many laboratories over several years . Five of the seven, including one recently isolated from the patient, were found to be similar to each other in sterol content, containing large amounts of fecosterol . Of the remaining two, one was thought to be a sensitive variant, both produced only small quantities of fecosterol and resembled the normal clinical strains and other azole-resistant strains in sterol content . The sterol composition of the Darlington strain was unique and apparently stable to prolonged in vitro experimentation and passage through the patient.

Br Vet J, 1990 Nov-Dec, 146(6), 519 - 30
The influence of a low cobalt intake on the neutrophil function and severity of Ostertagia infection in cattle; Paterson JE et al.; Two trials involving housed cattle examined the effect of Co depletion and supplementation on immune status as assessed by the neutrophil function test which measures the ability of isolated neutrophils to kill the yeast Candida albicans . A third trial investigated the extent to which Co status influenced the severity of Ostertagia ostertagi infection . In the first two trials liveweight gains were unaffected until some 40-60 weeks on the low dietary Co intake despite very low serum vitamin B12 values being recorded after 10 weeks . However, the immune status as measured by the neutrophil function test was reduced within 10 weeks of commencing the low Co diet . On administration of Ostertagia ostertagi larvae, Co-depleted cattle showed a greater weight loss than Co-supplemented cattle but showed no difference in the length of the prepatent period, worm egg production or serum gastrin and pepsinogen concentrations . After anthelmintic treatment both groups showed a similar response . It is postulated that the lowered immune response of Co-depleted cattle resulted in the greater severity of the Ostertagia ostertagi infection.

Acta Paediatr Scand, 1990 Nov, 79(11), 1031 - 8
Decreased adherence, chemotaxis and phagocytic activities of neutrophils from preterm neonates; Bektas S et al.; Using microanalytic assays various phagocytic functions of separated neutrophils from preterm neonates (mean birthweight 1,506 g, n = 13) were simultaneously studied . Adherence of neutrophils to nylon fibre was decreased in cells from preterm infants (77.1 +/- 3.1%) when compared with adult controls (86.9 +/- 2.1%, mean +/- 1 SD, p less than 0.05) . In addition neutrophil chemotaxis in response to zymosan activated serum was reduced in preterm neonates (131.9 +/- 19.7, adults 166.6 +/- 11.1, p less than 0.001); directed migration towards Formyl-Methionyl-Leucyl-Phenylalanine was also decreased (preterm neonates 93.4 +/- 15, adults 111.1 +/- 16.8, p less than 0.05) . Preterm infants had a higher percentage of slow moving neutrophils when compared with adults (p less than 0.001) . Phagocytosis of Candida albicans was reduced in neutrophils from preterm neonates (phagocytic index: preterm neonates 41.4 +/- 12.7, adults 83 +/- 7.2) . Adult neutrophils ingested more Candida per cell (p less than 0.001) . Chemiluminescence, exocytosis of elastase and lactoferrin during uptake of opsonized zymosan was also reduced in neutrophils from preterm neonates . However, random migration, phagocytosis of Staphylococcus aureus and production of O2- in response to Phorbol myristate acetate or opsonized zymosan were identical in cells from either source . We conclude, that these abnormalities of neutrophils could predispose the preterm infant to serious and often overwhelming bacterial and fungal infections.

J Dent Res, 1990 Nov, 69(11), 1717 - 23
Primary structure and anticandidal activity of the major histatin from parotid secretion of the subhuman primate, Macaca fascicularis; Xu T et al.; A major macaque histatin (M-histatin 1) from the parotid secretion of the subhuman primate, Macaca fascicularis, was isolated by gel filtration on Bio-Gel P-2 and purified to homogeneity by reversed-phase high-performance liquid chromatography on a TSK-ODS C18 column . The complete amino acid sequence of M-histatin 1, determined by automated Edman degradation, is: (formula; see text) M-histatin 1 contains 38 amino acid residues, a phosphoserine at residue 2, has a molecular weight of 4881.8, a calculated pI of 8.5, and histidine forms 26.3% of the mass . The hydropathicity plot of M-histatin 1 predicts that the molecule is entirely hydrophilic, and Chou-Fasman secondary prediction indicates that the polypeptide is devoid of alpha-helix and beta-sheet conformation in aqueous solutions but contains a series of beta turns . M-histatin 1 includes a six-amino-acid insert (residue 10-15) not present in human histatins and, with the introduction of gaps to maximize homology, it displays 89% and 91% sequence similarity with human histatins 1 and 3, respectively . M-histatin 1 exhibited fungicidal and fungistatic effects against the dimorphic pathogen, Candida albicans, in three separate bioassays . Its anticandidal effects were comparable with or greater than those of human histatins 1, 3, and 5 . M-histatins 2, 3, and 4 were not sequenced directly because insufficient materials were available, but the amino acid composition of M-histatin 3 was nearly identical to that of the N-terminal 20 amino acid residues of M-histatin 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Infect Immun, 1990 Nov, 58(11), 3810 - 2
Fab fragments from a monoclonal antibody against a germ tube mannoprotein block the yeast-to-mycelium transition in Candida albicans; Casanova M et al.; Fab fragments prepared from the immunoglobulin G monoclonal antibody (MAb) 4C12, which reacts with a determinant expressed on the hyphal extension of germ tubes of Candida albicans, inhibited germ tube formation, but intact MAb 4C12 did not . Indirect immunofluorescence showed a punctate binding pattern on cells incubated with Fab fragments but a confluent binding on cells incubated with intact MAb 4C12.

Infect Immun, 1990 Nov, 58(11), 3537 - 44
Immunoreactivity of neoglycolipids constructed from oligomannosidic residues of the Candida albicans cell wall; Faille C et al.; To establish a model to study the immunoreactivity of oligosaccharidic structures from the Candida albicans cell wall, we attempted to construct neoglycolipids with these residues by using oligomannosides released after mild acid hydrolysis of the phosphopeptidomannans isolated from yeast forms . From a mixture of manno-oligosaccharides ranging from mannobiose to mannononaose, the structure of a quantitatively major component (mannotriose) was determined to be Man (beta 1-2) Man (beta 1-2) Man alpha by 1H nuclear magnetic resonance analysis . After coupling of the pool of oligosaccharides to a lipid (4-hexadecylaniline), the synthesized molecules were injected into mice and rats . Antibody responses were detected on enzyme-linked immunosorbent assay plates coated with either phosphopeptidomannans or neoglycolipids . The hybrid molecules exhibited both immunogenicity and antigenicity . The kinetics of antibody responses as well as immunofluorescence patterns observed on whole C . albicans cells strongly mimicked results from the immunization of animals with natural antigens . Construction of neoglycolipids could therefore provide an interesting approach to the study of specific oligosaccharides of C . albicans and their recognition by the host immune system.

Infect Immun, 1990 Nov, 58(11), 3469 - 76
Partial biochemical characterization of cell surface hydrophobicity and hydrophilicity of Candida albicans; Hazen KC et al.; Hydrophobic yeast cells of Candida albicans are more virulent than hydrophilic yeast cells in mice . Results of experiments performed in vitro suggest that surface hydrophobicity contributes to virulence in multiple ways . Before definitive studies in vivo concerning the contribution of fungal surface hydrophobicity to pathogenesis can be performed, biochemical, physiological, and immunochemical characterization of the macromolecules responsible for surface hydrophobicity must be accomplished . This report describes our initial progress toward this goal . When hydrophobic and hydrophilic yeast cells of C . albicans were exposed to various enzymes, only proteases caused any change in surface hydrophobicity . Hydrophobic cell surfaces were sensitive to trypsin, chymotrypsin, pronase E, and pepsin . This indicates that surface hydrophobicity is due to protein . Papain, however, had no significant effect . The hydrophobicity of hydrophilic cells was altered only by papain . The proteins responsible for surface hydrophobicity could be removed by exposure to lyticase, a beta 1-3 glucanase, for 30 to 60 min . When 60-min lyticase digests of hydrophobic and hydrophilic cell walls were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with a 12.5% resolving gel, each protein population contained a single unique protein that was not evident in the other protein population . However, when the cell wall surface proteins of hydrophobic and hydrophilic cells were first labeled with 125I and then removed by lyticase and analyzed by SDS-PAGE, at least four low-molecular-mass (less than 65 kilodaltons) proteins associated with hydrophobic cells were either absent or much less abundant in the hydrophilic cell digests . This result was seen for both C . albicans strains that we tested . When late-exponential-phase hydrophilic cells were treated with tunicamycin, high levels of surface hydrophobicity were obtained by stationary phase . These results indicate that the surface hydrophobicity of C . albicans reflects changes in external surface protein exposure and that protein mannosylation may influence exposure of hydrophobic surface proteins.

Appl Environ Microbiol, 1990 Nov, 56(11), 3482 - 4
Effect of aflatoxins on rat peritoneal macrophages; Cusumano V et al.; Phagocytosis, intracellular killing of Candida albicans, and superoxide production by rat peritoneal macrophages exposed to aflatoxins B1, B2, G1, G2, B2a, and M1 at several times and concentrations were analyzed to evaluate the intensity of a depressive effect for each mycotoxin . All aflatoxins used at very low concentrations had a depressive effect on the functions of macrophages . The biggest impairment of phagocytosis, intracellular killing, and spontaneous superoxide production was observed in macrophages exposed to aflatoxins B1 and M1.

Mycoses, 1990 Nov-Dec, 33(11-12), 567 - 73
Clotrimazole and bifonazole in the topical treatment of Candida keratitis in rabbits; Behrens-Baumann W et al.; Using a reproducible model of Candida albicans keratitis in rabbits we studied the effect of topical clotrimazole and bifonazole . Candida albicans DSM 70010 (2.5 X 10(5) cells) was injected into the corneal stroma of both eyes of 28 rabbits . All eyes developed a corneal ulcer . Fourty-eight hours after inoculation the animals were divided into four groups: I (14 eyes) receiving 10 X clotrimazole 1% drops and subsequently removing the epithelium; II (14 eyes) receiving only clotrimazole drops; III (8 eyes) receiving 6 x bifonazole 1% drops and IV (19 eyes) serving as control (0.9% NaCl castor oil, untreated), 6 eyes of this group were also debrided . A further 6 rabbits were used respectively to judge if the drugs penetrated into the cornea and aqueous humor . There was a significant difference between the clotrimazole group with debridement (I) and the bifonazole group (IV) concerning hypopyon and complications (descemetocele, corneal perforation) . Clotrimazole penetrated into the cornea and after debridement into the aqueous humor . Bifonazole could not be identified in the cornea or aqueous humor.

Mycoses, 1990 Nov-Dec, 33(11-12), 527 - 37
Biotyping of Candida strains with regard to the epidemiology of candidosis . A practical approach; Tomsikova A et al.; In 62 strains of Candida albicans cultivated from specimens of patients with recurrent vaginal candidosis or with renal transplants, the biotypes were determined according to several characters: colony morphology, production of chlamydospores, auxanogram of C- and N-substances, zymogram, growth kinetics, adherence capability, proteolytic activity, sensitivity to 6 antimycotics, and serotypes . On the basis of this typing system the endogenous and exogenous sources of chronic vaginal candidosis as well as the sources of systemic candidosis in patients with renal transplants could be evaluated.

Mycoses, 1990 Nov-Dec, 33(11-12), 519 - 26
Indirect immunofluorescence staining and crossed immunoelectrophoresis for differentiation of Candida albicans and Geotrichum candidum; Jensen HE et al.; Rabbit hyperimmune antisera were used for differential diagnosis of Candida albicans and Geotrichum candidum in murine and bovine tissues by indirect immunofluorescence (IIF) staining . Although the antisera did not detect common antigens by crossed immunoelectrophoresis (XIE) a marked cross-reactivity of fungal cells was observed in the IIF assay . Following liquid phase absorption with heterologous antigenic preparations the hyperimmune antisera were rendered specific for each species thus making possible an unequivocal differentiation of the two species.

Zhonghua Min Guo Wei Sheng Wu Ji Mian Yi Xue Za Zhi, 1990 Nov, 23(4), 271 - 6
Effect of exogenous fat emulsion on phagocytic activity of polymorphonuclear cells in septic rats; Chen WJ et al.; The effect of exogenous fat emulsion on phagocytic activity of polymorphonuclear (PMN) cells in sepsis was studied in rats . The rats were divided into four groups . Group I, non-septic rats received saline infusion; group II, non-septic rats received exogenous fat emulsion; group III, septic rats received saline infusion; and group IV, septic rats received exogenous fat emulsion . Twenty hours after operation to induce sepsis, normal saline or exogenous fat emulsion was injected . Two hours later, the animal was sacrificed and the blood harvested . PMN cells were isolated from the blood, and phagocytic activity of the cells was studied by culture with Candida albicans . The results revealed that although sepsis led to a suppression of phagocytic function of PMN cells, infusion of exogenous fat emulsion had no deterious effect on the cell phagocytic activity in either septic or non-septic rats.

Immunobiology, 1990 Nov, 181(4-5), 276 - 87
Comparative activation states of tumor-associated and peritoneal macrophages from mice bearing an induced fibrosarcoma; Valdez JC et al.; Balb/c mice bearing a methylcholanthrene-induced fibrosarcoma were used to compare the activation levels of tumor-associated and peritoneal macrophages . Two stages of tumor growth were examined, namely "small" and "large" tumors, with average diameters of 10 and 30 mm, respectively . The activation state, determined by measurement of both phagocytic index and beta-glucuronidase content, was found to be markedly higher in tumor-associated macrophages than in their peritoneal counterparts and it was, in addition, independent of tumor progression . The percentage of tumor-associated macrophages, which were detected on the basis of Fc receptor expression, remained constant in the growing neoplasm, at approximately 23% of total cell population . None of these parameters were affected by inoculation with an immunopotentiating dose of heat-killed Candida albicans which, on the other hand, seemed not to alter the course of the tumor . These data suggest that within the tumor microenvironment macrophages would somehow be maintained at a constant proportion and at a highly activated state, while outside the tumor they would be at a lower activation level . Our results also suggest that TAM would not possess antitumor activity in vivo, although we have found this activity in vitro.

J Gen Microbiol, 1990 Nov, 136 ( Pt 11), 2149 - 54
Involvement of calcium, calmodulin and protein phosphorylation in morphogenesis of Candida albicans; Paranjape V et al.; N-Acetyl-D-glucosamine-induced germ tube formation in Candida albicans at 37 degrees C was accompanied by an increase in the rate of protein phosphorylation . The calmodulin antagonist trifluoperazine and the Ca2+ ionophore A23187, which inhibited germ tube formation, also reduced the rate of phosphorylation . The rate of phosphorylation was also reduced when cells were incubated at 25 degrees C, which favoured yeast-phase growth . Two-dimensional SDS-PAGE analysis of phosphoproteins from germ-tube-forming and yeast cells revealed two germ-tube-specific and three yeast-specific phosphoproteins . Germ tubes and hyphae had more calmodulin activity than yeast cells, irrespective of the germ-tube-inducing condition used . As a first step towards understanding the inhibitory effect of trifluoperazine on germ tube formation, calmodulin from C . albicans was purified to homogeneity . It was heat stable, and displayed a pronounced Ca2(+)-induced shift in electrophoretic mobility.

J Gen Microbiol, 1990 Nov, 136 ( Pt 11), 2143 - 8
Receptor-mediated elevation of adenylate cyclase by luteinizing hormone in Candida albicans; Williams RJ et al.; Human luteinizing hormone (hLH) and the GTP analogue guanosine 5'-O-(3-thio)triphosphate stimulated morphogenesis in the dimorphic fungal pathogen Candida albicans . hLH bound specifically to subcellular fractions from C . albicans and stimulated adenylate cyclase activity in C . albicans microsomes . We provide the first demonstration of guanine-nucleotide-binding proteins (G-proteins) in C . albicans, and propose that the stimulation of C . albicans morphogenesis by hLH is mediated by a receptor-coupled adenylate cyclase system involving G-proteins.

Nippon Ganka Gakkai Zasshi, 1990 Nov, 94(11), 1007 - 11
{The suppressive effect of intravenous fluconazole against endogenous candida endophthalmitis in rabbits}; Isobe Y et al.; The therapeutic effect of intravenous fluconazole against endogenous candida endophthalmitis was investigated in rabbits . Twelve albino rabbits and a candida strain isolated from the human vitreous were used . Endogenous candida endophthalmitis was made by intravenous inoculation of 8 x 10(5) candida albicans spores in rabbits . In the first of two series of experiments, three rabbits out of six were injected intravenously with 5 mg/kg.b.w . of fluconazole at 30 minutes, 1 day and 2 days after inoculation . Another three control rabbits received no medication . The clinical course of the eyes was observed for a week and the viable cell numbers of candida in the eye were counted at 7 days after inoculation . Three rabbits treated with fluconazole developed no ocular lesions and no candida spores whatsoever were isolated from the eyes . In contrast, three rabbits in the control group developed bilateral chorioretinitis and candida albicans was isolated from each of 6 eyes . In the second series, three out of six rabbits were injected intravenously of the same dose of fluconazole as described above for four days starting at 3 days after inoculation, when chorioretinitis was first observed . No medication was given to another three rabbits as a control . All six rabbits in this series developed chorioretinitis similarly and candida spores were isolated from all eyes at 7 days after inoculation . These results show that intravenous fluconazole is effective in the prevention of the endogenous candida endophthalmitis in rabbits but ineffective for these short term therapeutic applications after onset.

J Gen Microbiol, 1990 Nov, 136 ( Pt 11), 2155 - 63
Lymphoproliferative and cytotoxic responses of human peripheral blood mononuclear cells to mannoprotein constituents of Candida albicans; Torosantucci A et al.; Two major proteoglycan constituents (designated F1 and F2) of the cell wall of Candida albicans were separated by ion-exchange chromatography from a crude carbohydrate-rich extract (GMP), and investigated for their chemical and molecular composition, antigenicity and immunomodulatory properties in cultures of human peripheral blood mononuclear cells (PBMC) . Both fractions consisted predominantly of Periodic acid-Schiff (PAS) and concanavalin A (Con A)-reactive material consisting of greater than 90% mannose, 3-5% protein and small amounts of phosphorus; each was recognized by an anti-Candida rabbit serum as well as by a monoclonal antibody (mAb AF1) directed against an oligosaccharide epitope present on the fungal cell surface . When F1 and F2 were subjected to SDS-PAGE, transblotted and stained with enzyme-conjugated mAb AF1 or Con A, most of the antibody or lectin bound to high molecular mass (greater than 200 kDa) polydisperse material, some of which was present in F2 (as in the starting GMP extract) but absent in F1 . This difference was also observed in PAS-stained gels of the two fractions . The F2, but not the F1, constituent was as active as the unfractionated GMP extract in inducing lymphoproliferation, production of the cytokines interleukin-2 and interferon-gamma, and generation of cytotoxicity against a natural-killer-sensitive target cell line (K562) . These immunomodulatory properties were, like those possessed by GMP, protease-sensitive and heat-stable . Treatment of PMBC cultures with a modulatory anti-T-cell receptor antibody abolished the lymphoproliferation induced by GMP and F2 but not that induced by phytohaemagglutinin, showing that the mannoprotein materials of C . albicans acted through interaction with the antigen receptor complex.

N Z Med J, 1990 Oct 24, 103(900), 505 - 7
The spectrum of systemic candidiasis at Auckland Hospital; Fraser AG et al.; Systemic candidiasis is uncommon . We reviewed our experience with this disease from the infectious disease unit, Auckland Hospital, between 1982 and 1988, because many of these patients are referred to us . We then selected 11 of them to highlight particular presentations, diagnostic or management issues . We included both compromised and noncompromised patients from medical and surgical services . Candida albicans was the most common cause, but we also saw patients infected with C glabrata, C parapsilosis, and C tropicalis and present them to exemplify their different clinical presentations . Demonstrable fungaemia is uncommon in patients with systemic candidiasis, serological techniques are both insensitive and nonspecific and patients are often too ill from underlying disease to allow for invasive diagnostic procedures . Thus diagnosis is often difficult . Parenteral amphotericin B with or without 5-fluorocytosine is still the main antifungal treatment . Triazole antifungals may change that in the future . Systemic candidiasis retains a high mortality: careful individualised management of patients may improve mortality and morbidity.

Blood, 1990 Oct 15, 76(8), 1580 - 5
Effect of recombinant human granulocyte-macrophage colony-stimulating factor administration on the lymphocyte subsets of patients with refractory aplastic anemia; Faisal M et al.; Human recombinant granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was administered to 14 patients with refractory aplastic anemia (AA) . The effect of rhGM-CSF therapy on the lymphocyte phenotype; on the proliferative responses to the mitogen phytohemagglutinin, Candida albicans, and tetanus toxoid antigens; and on the natural killer (NK) activity of the circulating lymphocytes was studied . Samples were collected before (baseline) and twice during the rhGM-CSF administration . The absolute number of circulating lymphocytes remained relatively constant during the first period, but experienced a significant increase (P less than .001) during the second period . The increase was most prominent in the B cells (P less than .001), but the T cells (P less than .016) also increased . Detailed investigation of lymphocyte subsets showed an increase of the markers CD38 (Leu17), HLA-DR, and the transferrin receptor throughout the treatment course giving evidence of lymphoid cell activation . The NK cell activity was suppressed (P less than .008) throughout the treatment . However, proliferative responses to phytohemagglutinin, Candida antigen, and tetanus toxoid were unaffected . Although the mechanism is not yet defined, GM-CSF does induce activation and increase in absolute lymphoid cell number, especially B cells, together with a decrease in NK cytotoxicity . The implication of these immune cell changes in relation to host resistance to microorganisms remains to be established.

Tidsskr Nor Laegeforen, 1990 Oct 10, 110(24), 3123 - 4
{Intraocular Candida albicans infection}; Bakken A; The article discusses three patients with an intraocular Candida albicans-infection . Vitrectomy was performed on two patients in whom the infection occurred after abdominal surgery . Both had significant corpus vitreum involvement . One of these patients regained good visual acuity, while in the other patient preretinal proliferation caused permanently reduced vision . The third patient had only chorioretinal involvement . After intracranial surgery for acusticus neurinoma his general condition deteriorated and he developed septicemia . He was treated with intravenous amphotericin B and visual acuity returned to normal . Early diagnosis and treatment are important for satisfactorily preservation of vision . Therefore patients in risk groups with ocular complaints should be referred immediately to an ophthalmologist . Early diagnostic and therapeutic vitrectomy should be considered for all patients with suspected vitreous involvement.

Antimicrob Agents Chemother, 1990 Oct, 34(10), 1996 - 2006
19F nuclear magnetic resonance study of fluoropyrimidine metabolism in strains of Candida glabrata with specific defects in pyrimidine metabolism; Fasoli MO et al.; Flucytosine (5-FC)-resistant strains were isolated from the haploid opportunistic pathogen Candida glabrata by UV-induced mutation and fluoropyrimidine selection . These strains were characterized biochemically, and the metabolism of fluorinated pyrimidines was studied by 19F nuclear magnetic resonance spectroscopy . No evidence was obtained from these studies for degradative metabolism of the fluorinated derivatives . In the parental susceptible strain of C . glabrata, 5-fluorouracil but not 5-FC was detected within the cells . 5-Fluorouracil was also present in the culture supernatant after incubation of the cells with 5-FC . The distribution of fluorinated derivatives within the 5-FC-resistant strains was consistent with their genotype . Two strains of C . glabrata which had only a partial loss of cytosine deaminase and UMP pyrophosphorylase activity had high levels of resistance to 5-FC . Both C . glabrata and Candida albicans were susceptible to 5-fluorouridine . This compound but not the anticancer drug 5-fluoro-2-deoxyuridine was shown to be transported into susceptible cells by a specific uridine permease.

J Clin Pharm Ther, 1990 Oct, 15(5), 365 - 9
Microbial contamination and preservation efficacy of cough preparations; Na'was TE et al.; Cough syrups, manufactured by four different Jordanian pharmaceutical companies, were examined for microbial contents and efficacy of preservation from fungal and bacterial contamination . Five per cent of the tested samples were found to be contaminated by Candida albicans and 30% of the products examined did not comply with the pharmacopoeial requirements for optimal preservation from fungal contamination . All the products tested were free from bacteria and were efficiently preserved against accidental bacterial contamination.

J Gen Microbiol, 1990 Oct, 136 ( Pt 10), 1937 - 43
Inhibition of the dimorphic transition of Candida albicans by the ornithine decarboxylase inhibitor 1,4-diaminobutanone: alterations in the glycoprotein composition of the cell wall; Martinez JP et al.; Hyphal development in Candida albicans was selectively blocked by the ornithine decarboxylase competitive inhibitor 1,4-diaminobutanone (DAB) . Inhibition of hyphal development required DAB during both yeast inoculum growth and subsequent incubation at 37 degrees C to induce mycelial growth . This effect was not due to general growth inhibition since DAB did not inhibit yeast growth, and reduced protein synthesis by 30% at most . Moreover, protein synthesis was unaffected by DAB when cells were pre-grown in drug-containing media . Since DAB inhibited dimorphic transition at 37 degrees C, morphology- and temperature-dependent protein synthesis could be distinguished . DAB stimulated the synthesis of several yeast wall-proteins, irrespective of morphology or growth temperature, and two at 37 degrees C only, but it inhibited the synthesis of a single mycelial-specific glycoprotein species.

J Gen Microbiol, 1990 Oct, 136 ( Pt 10), 1925 - 36
Switching at the cellular level in the white-opaque transition of Candida albicans; Bergen MS et al.; The 'white-opaque transition' in Candida albicans strain WO-1 provides a unique system for analysing high-frequency switching at the cellular level because of the difference in the budding phenotypes of the white and opaque phases . Single white and opaque cells were placed on agar and monitored for the dynamics of cell division, microcolony genesis and switching to the alternative phase . It is demonstrated that at 24 degrees C, opaque cells can switch directly to white cells but white cells first generate an elongate, pseudohyphal-shaped precursor in the transition to an opaque cell . Cells in either phase can generate a daughter cell in the alternative phase, then revert immediately to the genesis of subsequent daughter cells in the original phase . By developing a mathematical model for switching at the cellular level which subtracts mother cells and switched daughter cells from the pool of switching candidates, the probability for an opaque cell to generate a white daughter cell in any single generation was calculated to be 1.0 x 10(-1) and the probability for a white cell to generate an opaque daughter cell in any single generation was calculated to be 1.7 x 10(-5) at 24 degrees C on nutrient agar . The mean number of generations before an opaque cell generated a white daughter cell was calculated to be 3.4 and the mean number before a white cell formed an opaque cell was calculated to be 15.8 at 24 degrees C on nutrient agar . Finally, high-temperature induction of the opaque to white transition was analysed at the cellular level and demonstrated to involve frequent bipolar formation of white daughter cells on the original opaque mother cell, and in some cases intermediate phenotypes.

FEMS Microbiol Immunol, 1990 Oct, 2(3), 147 - 53
Structures involved in the binding of human fibrinogen to Candida albicans germ tubes; Annaix V et al.; Recent evidence for the interaction between human fibrinogen and Candida albicans germ tubes have led us to attempt to characterize the structures involved . Using 125I-radiolabeled proteins, fibrinogen purified by affinity chromatography and its plasmin degradation products, the binding sites on the fibrinogen molecule appeared to be located specifically in the D-domain . Conversely to the fibrinogen and the fragment D, radiolabeled fragment E, however, did not interact with cells . The binding was time-dependent, saturable and reversible . Scatchard analysis of the data obtained revealed an average of 6000 binding sites per germ tube with dissociation constant (Kd) of 5.2 X 10(-8) M . No potent competition was observed for a range of different proteins and carbohydrates . Fibrinogen fragment D binding proteins were identified using a dithiothreitol-iodoacetamide extract of the fungus . By sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting, one component of 68 kDa was detected . Thus, the presence of fibrinogen binding proteins specifically localized on the cell wall surface of C . albicans germ tubes may constitute one of the factors involved in the development of candidosis.

J Autoimmun, 1990 Oct, 3(5), 523 - 30
Spontaneous antibody-secreting cells against DNA and common environmental antigens in systemic lupus erythematosus; Dar O et al.; Cells spontaneously secreting IgG or IgM antibodies to DNA or to common environmental antigens--influenza virus haemagglutinin, adenovirus hexon and mannan from Candida albicans--have been enumerated by ELISA spot in blood from patients with systemic lupus erythematosus (SLE) and normal donors . Mean values were raised for all antigens in the disease, with those for DNA being no greater than for the other antigens . In normal donors, levels of IgM-secreting cells were similar for DNA and the environmental antigens whereas virtually no IgG anti-DNA secreting cells were found . When results were expressed relative to total numbers of IgG or IgM-secreting cells, the differences between the groups disappeared or were greatly reduced in all systems except IgG anti-DNA . These findings are consistent with a requirement for both polyclonal activation and a self-antigen response in the production of IgG autoantibodies in SLE.

Ophthalmic Surg, 1990 Oct, 21(10), 726 - 8
Retinal toxicity and in vitro efficacy study of cilofungin (LY121019); Shahsavari M et al.; We assessed the retinal toxicity of a new antifungal agent, cilofungin, by injecting it into the vitreous body of albino rabbit eyes in dosages of 2.5 micrograms to 320 micrograms . The maximum intravitreal drug concentration (320 micrograms) produced no histological evidence of retinal toxicity . Electroretinography data showed some variations, but no toxicity at the highest dose (320 micrograms) . When efficacy was evaluated in vitro against Candida albicans, the minimal inhibitory concentration was 2.50 micrograms/mL, using Sabouraud's broth or M3 medium . The minimal fungicidal concentration was 5 micrograms/mL with Sabouraud's broth, and 10 micrograms/mL with M3 medium . Cilofungin is a potentially safe antifungal for the treatment of candida endophthalmitis.

Genitourin Med, 1990 Oct, 66(5), 357 - 60
Intermittent prophylactic treatment of recurrent vaginal candidiasis by postmenstrual application of a 500 mg clotrimazole vaginal tablet; Roth AC et al.; The therapeutic efficacy of intermittent, monthly, postmenstrual prophylaxis with a single 500 mg clotrimazole vaginal tablet (n = 33) was compared with placebo tablets (n = 29) in 62 woman (age 28.1, SD 7.2 years) with recurrent vulvovaginal candidiasis . The number of episodes of acute vulvovaginal candidiasis experienced during the year prior to inclusion was 6.3, SD 1.9 . The cumulative recurrence frequency after 6 months intermittent prophylaxis with clotrimazole (30.3%) was lower (p less than 0.001) than that recorded for the women who received placebo (79.3%) . After an additional 6 months observation period without treatment there was no significant difference in the cumulative recurrence frequency between the groups (clotrimazole 84.9%; placebo 86.2%) . The vagina was recolonised with Candida albicans in 70% of the women after 6 months prophylactic treatment with clotrimazole and in 86% of the women who had received placebo . Thus, this study has demonstrated that postmenstrual prophylactic treatment with a single 500 mg clotrimazole vaginal tablet, applied monthly, prevents recurrence of symptoms, although it does not eliminate yeasts from the vagina.

Ann Surg, 1990 Oct, 212(4), 496 - 510; discussion 511-2
The process of microbial translocation; Alexander JW et al.; The process of microbial translocation was studied using Candida albicans, Escherichia coli, or endotoxin instilled into Thiry-Vella loops of thermally injured guinea pigs and rats . Translocation of C . albicans occurred by direct penetration of enterocytes by a unique process different from classical phagocytosis . Translocation between enterocytes was not observed . Internalization was associated with a disturbance of the plasma membrane and brush border, but most internalized organisms were not surrounded by a plasma membrane . Passage of the candida into the lamina propria appeared to be associated with disruption of the basal membrane with extrusion of cytoplasm of the cell and candida . Organisms in the lamina propria were commonly phagocytized by macrophages but also were found free in lymphatics and blood vessels . Translocation of E . coli and endotoxin also occurred directly through enterocytes rather than between them, but translocated endotoxin diffused through the lamina propria and muscular wall of the bowel wall by passing between rather than through the myocytes . These descriptive phenomena provide new insight into the role of the enterocyte and intestinal immune cells in the translocation process.

Arch Dermatol, 1990 Oct, 126(10), 1334 - 6
Severe phototoxic burn following celery ingestion; Ljunggren B; A 65-year-old woman developed a severe, generalized phototoxic reaction following a visit to a suntan parlor . History taking revealed that she had consumed a large quantity of celery root (Apium graveolens) 1 hour earlier . With the use of thin-layer chromatography, methoxsalen (8-methoxypsoralen) and 5-methoxypsoralen were identified in the extract from a similar celery root . The biologic activity of this extract, as evaluated with the semiquantitative Candida albicans inhibition technique, indicated a total psoralen dose of approximately 45 mg . Substantial amounts of psoralen may be absorbed from vegetables, such as celery, and under unusual circumstances, this may constitute a health hazard.

Obstet Gynecol, 1990 Oct, 76(4), 651 - 5
Torulopsis glabrata vaginitis: clinical aspects and susceptibility to antifungal agents; Redondo-Lopez V et al.; Torulopsis glabrata is second only to Candida albicans in frequency of isolation from the vagina in both asymptomatic women and patients with yeast vaginitis . We retrospectively studied 33 patients from whom vaginal isolates of T glabrata were obtained . Torulopsis glabrata caused symptomatic vaginitis in 42% of the patients but was unassociated with symptoms in 30%; in 27% of patients, its importance was uncertain because of concomitant pathology . Antifungal susceptibility testing was performed on 39 T glabrata strains isolated from 39 patients . The minimal inhibitory concentrations (MICs) of the majority of T glabrata isolates fell within the sensitive range of the antimycotic drugs tested; however, no correlation was found between in vitro antifungal MICs and the response to azole drug therapy . Clinical success was achieved in 67% of the patients although mycologic cure occurred in only 33% . A small number of patients developed recurrent and often chronic Torulopsis vaginitis unresponsive to conventional therapy . Limited experience suggests that vaginal boric acid therapy may be of value in these recalcitrant cases.

CMAJ, 1990 Oct 1, 143(7), 641 - 6
Gastrointestinal function and structure in HIV-positive patients; Sutherland LR et al.; We examined 19 patients (17 men) with human immunodeficiency virus (HIV) infection and gastrointestinal symptoms to determine whether those symptoms were due to either a gastrointestinal tract infection or a defect in mucosal absorption because of an enteropathy . The erythrocyte folate and serum vitamin B12 levels were within normal limits in all of the patients . The serum ferritin level was elevated in 12 . The xylose absorption test results were abnormal in 8 of the 13 patients able to complete the study . None of the duodenal aspirates yielded a pathogen . Light microscopy revealed nonspecific lymphocytic inflammation without infection in the stomach (in seven patients), the esophagus (in five), the duodenum (in two) and the rectum (in two) . However, biopsy specimens were positive for Candida albicans in the esophagus (four patients), cytomegalovirus in the esophagus (one) and the rectum (two), Helicobacter pylori in the antrum (two), Treponema infection in the rectum (two) and Mycobacterium avium-intracellulare in the small intestine (one) . Only three patients had a normal series of biopsy specimens . All of the patients had similar ultrastructural changes at the epithelial-stromal junction of the antral glands and in the intestinal crypts . We conclude that abnormal biochemical and endoscopic findings are common in HIV-positive patients with gastrointestinal symptoms . Defects in carbohydrate absorption and ultrastructural changes may be responsible for some aspects of HIV enteropathy.

Blood, 1990 Oct 1, 76(7), 1405 - 9
Release of tumor necrosis factor by human polymorphonuclear leukocytes; Djeu JY et al.; Evidence is presented that human polymorphonuclear neutrophils (PMN) can be induced to produce tumor necrosis factor (TNF) . Other investigators have previously reported that TNF has been induced from macrophages by bacteria and, more recently, from natural killer cells by certain tumor cells . Our laboratory has reported that the opportunistic fungi, Candida albicans, can induce TNF, not only from human monocytes, but also from Percoll-fractionated large granular lymphocytes . We now report that incubation of PMN with C albicans for 3 hours was sufficient for detection of TNF release, and peak induction was observed at 8 to 18 hours . This release was inhibitable by actinomycin D, an inhibitor of RNA synthesis, as well as by emetine and cycloheximide, which block protein synthesis . The TNF produced by PMN was neutralized by specific monoclonal antibodies against human TNF . These results represent an important finding that TNF production is a normal response of PMN to stimulation by fungi such as C albicans and suggest that the release of TNF may be related to autocrine activation of PMN effector function to control Candida growth.

Zhonghua Yi Xue Za Zhi (Taipei), 1990 Oct, 46(4), 195 - 201
Cross-reactivity among antigens of different air-borne fungi detected by ELISA using five monoclonal antibodies against Penicillium notatum; Shen HD et al.; Cross-reactivity among antigens of 12 genera of air-borne fungi, 13 species of Penicillium, and 5 species of Aspergillus was studied by ELISA using five monoclonal antibodies (MoAbs) against Penicillium notatum . Epitopes recognized by all the five MoAbs were susceptible to treatment of mild periodate oxidation and may therefore be associated with carbohydrates . Furthermore, our results showed that there is cross-reactivity among antigens of Penicillium, Aspergillus, and Eurotium species . By using these MoAbs, cross reactivity was not detected between antigens of Penicillium notatum and antigens of Fusarium solani, Alternaria porri, Cladosporium cladosporoides, Curvularia species, Nigrospora species, Aureobasidium pullulans, Wallemia species, Rhizopus arrhizus, and Candida albicans . Cross-reactivity among antigens of 11 species of Penicillium and 5 species of Aspergillus could be detected by ELISA using one of the five MoAbs (MoAb P15) . The fact that there may be cross-reactivity among antigens of closely related fungi species should be considered in the diagnosis and treatment of mold allergic diseases.

Zh Mikrobiol Epidemiol Immunobiol, 1990 Oct, (10), 109 - 12
{The phenotypic expression of the genes controlling the yield of a factor suppressing macrophage migration to Candida albicans antigens and tuberculin in mice}; Vorob'ev KV et al.; The regulation of the synthesis of factor inhibiting the migration of macrophages in response to C . albicans antigen in CBA (H-2k) and C57BL/6 (H-2b) mice has been studied . The low level of macrophage migration inhibition factor in response to this antigen is due to the existence of cyclophosphamide-inhibited specific suppressors . Differences between various strains of mice ensue from different activity of suppressors of thymic origin, whose nature has been revealed as the result of the transfer of marrow cells treated with anti-Thy-1 serum.

Biochem Int, 1990 Oct, 22(1), 11 - 20
Defective plasma membrane H(+)-ATPase or orthovanadate resistant mutants from Candida albicans, a pathogenic yeast; Mahanty SK et al.; Orthovanadate-resistant mutants of diploid yeast Candida albicans were isolated by using two step mutational process . Such mutants had altered plasma membrane H(+)-ATPase activity . Based on the levels of PM-ATPase activity, these mutants could be grouped into two categories; one group included those mutants which did not exhibit reduction in PM-ATPase activity while the other displayed a reduction of upto 40% in enzyme activity . These mutants exhibited a number of distinct phenotypic characteristics and altered abilities with regard to phenotypic divergence . Results demonstrate the importance of PM-ATPase in overall physiology of this pathogenic yeast.

Infect Immun, 1990 Oct, 58(10), 3319 - 24
Role of granulocytes in increased host resistance to Candida albicans induced by recombinant interleukin-1; Kullberg BJ et al.; The effect of human recombinant interleukin-1 alpha (IL-1 alpha) on a systemic candidal infection in mice under various conditions of immunosuppression was investigated . In normal mice and in mice pretreated with cyclophosphamide, hydrocortisone acetate, or sublethal total body irradiation, the outgrowth of Candida albicans in the kidney was significantly reduced by the administration of a single intraperitoneal dose of 80 ng of IL-1 (P less than 0.05) . In mice treated with either cyclophosphamide or irradiation, IL-1 also significantly reduced the outgrowth of C . albicans in the spleen . The protective effect of IL-1 was present when given 24 h before injection of C . albicans but also when IL-1 was given simultaneously with or 6 h after injection of C . albicans in cyclophosphamide-treated mice . The effect of IL-1 was independent of the presence or recruitment of granulocytes, since IL-1 inhibited the outgrowth of C . albicans in the kidneys and spleens of mice that were rendered severely granulocytopenic (less than 50 granulocytes per mm3) throughout the duration of the infection by either repeated injections of cyclophosphamide or sublethal total body irradiation . These results indicate that the enhancement of host resistance by IL-1 is not due solely to increased granulocytopoiesis or chemotaxis of granulocytes but strongly suggest that other mechanisms play a role in the protective effect of IL-1 against systemic infections.

J Med Chem, 1990 Oct, 33(10), 2755 - 9
Antimicrobial properties of N3-(iodoacetyl)-L-2,3-diaminopropanoic acid-peptide conjugates; Andruszkiewicz R et al.; Six peptide conjugates consisting of either norvaline, methionine, or lysine and N3-(iodoacetyl)-L-2,3-diaminopropanoic acid--a strong, irreversible inactivator of bacterial and fungal glucosamine-6-phosphate synthase--were synthesized and their antibacterial and antifungal activities were evaluated . Antimicrobial potencies of these peptides were correlated with their transport and cleavage rates inside the cells . Bacteriolysis of Bacillus pumilus cells and inhibition of {14C}glucose incorporation into cell-wall polysaccharides of Candida albicans as a result of glucosamine 6-phosphate inactivation were also observed . Reversal of growth inhibitory effect of these peptides by N-acetylglucosamine in bacteria and fungi suggests the effective delivery of N3-iodoacetyl-L-2,3-diaminopropanoic acid into the cell by a peptide-transport system.

J Biol Regul Homeost Agents, 1990 Oct-Dec, 4(4), 142 - 9
A mannoprotein constituent of Candida albicans cooperates with antigen in the induction of a specific primary antibody response in cultures of human lymphocytes; Luzzati AL et al.; The effects of Candida albicans mannoproteins on the induction of a primary antibody response to a T-dependent antigen, sheep erythrocytes (SRBC), in cultures of human blood lymphocytes, were investigated . Two experimental systems (bulk and limiting dilution cultures) allowing the detection of both enhancing and inhibitory effects, were used . In bulk cultures, antigen alone elicited a small number of specific antibody forming cells, unless IL-2 was supplied . Addition of the fungal mannoprotein extract or of a purified constituent of it increased 5 to more than 10 times the specific response . When limiting dilution analysis was performed, we observed that: a) a similar number of specific precursor cells was induced by antigen and either IL-2 or mannoprotein; b) the plot of the number of seeded cells versus the log of the fraction of negative cultures was linear in antigen and IL-2 triggered cultures but constantly deviated from linearity when the candidal stimulant was added . Thus, more than one type of precursor cell was limiting in these cultures, and the immunoenhancing effect of mannoprotein may involve multiple cellular interactions.

Zh Mikrobiol Epidemiol Immunobiol, 1990 Oct, (10), 35 - 8
{The interaction of neutrophilic granulocytes with Candida albicans fungi in the formation of mycotic foci under conditions of immunodepression}; Khokhlov SE et al.; In the electron-microscopic study of the interaction of neutrophil granulocytes with the fungal species C . albicans in the process of the formation of mycotic foci in mice under the conditions of cyclophosphamide-induced immunosuppression, mouse leukocytes have been found to retain their capacity for migration to the focus of inflammation and for the phagocytosis of fungal cells . At the same time the fungicidal activity of leukocytes is decreased, which is manifested by the prevalence of viable fungal cells with the partially digested cell wall in the cytoplasm of leukocytes.

J Formos Med Assoc, 1990 Oct, 89(10), 863 - 7
Fungemia: analysis of 43 cases; Lin HH et al.; This report reviews the cases of 43 patients with 48 episodes of fungemia, and examines the clinical significance of fungemia and the results of treatment . All episodes were nosocomial infections . Candida albicans (60.4%), Candida parapsilosis (16.7%), and Candida tropicals (14.6%) were the most common fungal pathogens isolated from blood cultures . Patients with Candida albicans had a better survival rate than those with other species (p = 0.011) . Polymicrobial fungemia was noted in 5 patients (11.6%) . Most patients had underlying diseases and predisposing factors . Intravascular catheters (100%), broad-spectrum antibiotics administration (100%), surgical procedures (46.5%) and total parental alimentation (41.9%) were the most common predisposing factors . The clinical manifestations were not characteristic and consisted of nonspecific signs of sepsis . The overall mortality rate was 79% . We did not find any improvement in the mortality rate of our patients treated with amphotericin B . Early recognization, immediate removal of predisposing factors, and correction of underlying conditions is most important for patients with fungemia . We also suggest that fungal infection should be considered early when a febrile patient at high risk dose not improve with broad-spectrum antibacterial therapy.

Clin Microbiol Rev, 1990 Oct, 3(4), 321 - 34
Candida albicans strain delineation; Merz WG; Candida albicans is a major opportunistic pathogen causing a wide spectrum of disease in human beings . Methods for strain delineation of this species to assess or predict virulence or to conduct epidemiologic or pathogenetic investigations have been developed . Although factors associated with virulence have been identified, there is no rapid system to quantitate them in a clinical laboratory . Therefore, many typing methods are based on variable phenotypic characteristics within this species including morphotyping, serotyping, antibiogram, resistogram typing, biotyping, biotyping based on commercial carbon assimilation patterns, enzyme profiles, sensitivity to yeast killer toxins, and typing based on protein variability . Phenotypically defined strains generally do not correlate with the pathogenic potential of a strain with the exception of morphotyping . However, these methods can be useful in epidemiologic investigations; for example, they have revealed that most individuals harbor one strain and that infections are frequently due to an endogenous strain . Problems with these methods usually relate to their discriminatory power . When this is maximized, reproducibility (especially between laboratories) suffers . Recently, methods based on differences in DNA structure (genotyping) for strain delineation have been developed, including electrophoretic karyotyping and restriction enzyme fragment length polymorphisms . The development of a computer-assisted data bank and analysis for these genotypic strain delineators will open investigations into the pathogenesis of this infection and permit epidemiologic studies previously not possible with this important human pathogen.

Microbiologica, 1990 Oct, 13(4), 347 - 51
Antifungal chemoprophylaxis in cancer children: a prospective randomized controlled study; Caselli D et al.; We report a prospective, randomized, controlled study of antifungal chemoprophylaxis in forty immunocompromised children with hematologic malignancies, receiving respectively itraconazole, ketoconazole, amphotericin-B and no prophylaxis . Fungal isolates from patients' saliva or stools were obtained from 19/40 patients (Candida albicans from 15 patients) . Disseminated infection was never observed . Fungal isolates were significantly less frequent in the ketoconazole group of patients vs any other group . Systemic antifungal chemoprophylaxis with ketoconazole appears more effective even than the recently introduced itraconazole.

Zh Mikrobiol Epidemiol Immunobiol, 1990 Oct, (10), 106 - 9
{Cross-reacting Candida albicans antigens in the pathogenesis of candidiasis}; Karaev ZO et al.; Organ- and tissue-specific antigens with affinity to C . albicans have been detected in some organs and tissues of the body . The occurrence of C . albicans colonization of different organs correlates with the presence of cross-reacting antigens in these organs.

J Immunol Methods, 1990 Sep 14, 132(2), 205 - 9
Detection by immunofluorescent anti-idiotypic antibodies of yeast killer toxin cell wall receptors of Candida albicans; Polonelli L et al.; Yeast killer toxin cell wall receptors of Candida albicans were observed by indirect immunofluorescence using an affinity purified rabbit anti-idiotypic antiserum . The antiserum had been raised against a monoclonal antibody neutralizing the in vitro activity of a killer toxin produced by a selected strain of Hansenula anomala UCSC 25F . This simple procedure permitted the location of killer toxin cell wall receptors in various morphological phases of the yeast cells . The use of the indirect immunofluorescence technique with anti-idiotypic antibodies may have potential value in determining the occurrence of killer toxin receptors in other microbial systems.

Arch Intern Med, 1990 Sep, 150(9), 1929 - 33
The limited value of symptoms and signs in the diagnosis of vaginal infections; Schaaf VM et al.; The etiology of vaginitis can be difficult to prove . To determine the relationship between clinical criteria (symptoms and signs) and three causes of vaginitis, we prospectively evaluated 22 criteria in 123 unselected symptomatic patients . Diagnoses of Candida albicans and Trichomonas vaginalis infection were based on culture . Bacterial vaginosis was defined by the presence of 3 of 4 clinical criteria . Only 49% of our patients received diagnoses, and itching was the only symptom more frequently noted among those with diagnoses . Symptoms did not differ among the three infections, and lack of vaginal odor in yeast infection was the only significantly different physical sign . Yeast and trichomonads were seen on microscopy in 63% and 75% of culture-positive specimens . Bacterial vaginosis had no significant clinical criteria beyond those that defined the diagnosis . We conclude that presenting symptoms and signs in vaginitis evaluation have limited value, and that half of the women with vaginitis may lack a microbiologic diagnosis.

Chem Pharm Bull (Tokyo), 1990 Sep, 38(9), 2476 - 86
Triazole antifungals . II . Synthesis and antifungal activities of 3-acyl-4-methyloxazolidine derivatives; Konosu T et al.; Triazole compounds with an oxazolidine ring were designed and synthesized as a potential inhibitor of the fungal cytochrome P450 14 alpha-demethylase . In testing for antifungal activity against a mouse systemic Candida albicans infection, (4R,5R)-3-acyl-4-methyloxazolidine derivatives 4 exhibited remarkably high efficacy after oral or parenteral dosing . The potent activity of 4 is hypothesized to be a consequence of a structural similarity between 4 and lanosterol, a target molecule of the cytochrome P450 14 alpha-demethylase . Highly stereoselective synthesis of these oxazolidines is also described.

J Int Med Res, 1990 Sep-Oct, 18(5), 389 - 99
A comparison of butoconazole nitrate cream with econazole nitrate cream for the treatment of vulvovaginal candidiasis; Ruf H et al.; In a randomized, single-blind, parallel study the safety and efficacy of 2% butoconazole nitrate cream used for 3 days were compared with those of 1% econazole nitrate cream used for 7 days at night in patients with vulvovaginal candidiasis . Patients in both treatment groups had positive potassium hydroxide smears and fungal cultures, and were similar in age, disease duration and history, obstetric history and contraceptive use . Of the 75 patients enrolled, 63 with a Candida albicans infection were included in the efficacy analyses . Evaluations were made at the start of the study (visit 1), after 10-23 days (visit 2) and after 24-45 days (visit 3) . Both drugs significantly reduced all signs and symptoms, and at visits 2 and 3 the percentages of patients considered microbiologically, clinically and therapeutically cured were consistently higher for butoconazole- than for econazole-treated patients, although differences were not statistically different . Although both drugs were safe and well tolerated, it is concluded that butoconazole because of its much shorter regimen and superior clinical and microbiological performance was the drug of choice.

Clin Exp Allergy, 1990 Sep, 20(5), 549 - 54
IgE, IgA and IgG antibodies and delayed skin response towards Candida albicans antigens in atopics with and without saprophytic growth; Savolainen J et al.; Immunoblotting and RAST were used to analyse IgE, IgA and IgG responses to antigens of Candida albicans . These were compared with the delayed skin response and C . albicans carriage in 40 atopic subjects . The majority of the atopic patients showed a strong IgG and IgA antibody response towards mannan, a carbohydrate, but only occasionally to proteins . Altogether 22 of the 40 patients showed specific IgE towards C . albicans by immunoblotting . The IgE response was mainly towards proteins, particularly to ones with molecular weights of 29 kD and 46 kD, and only in eight out of 22 IgE-positive subjects towards mannan . The IgG and IgA responses to mannan and the total IgE response towards C . albicans assessed by RAST showed an association with C . albicans carriage, whereas the delayed skin response showed an inverse relationship . The immunological parameters characteristic of C . albicans carriage were found to be C . albicans-specific depressed delayed skin response and elevated IgE, IgA and IgG responses . This situation in the atopics presenting such parameters may favour simultaneous sensitization and exposure by colonization . The degree of sensitization may be sufficiently high to produce symptomatic allergy, such as asthma, in some individuals during occasional overgrowth of C . albicans, e.g . due to antibiotic therapy.

Pathol Biol (Paris), 1990 Sep, 38(7), 719 - 22
{In vitro antifungal activity of mercurobutol}; Boiron P; Mercurobutol, in its commercial form, exhibits fungistatic and fungicidal activities against both yeasts: Candida albicans, C . tropicalis, Torulopsis glabrata, Pityrosporum spp., and filamentous fungi: dermatophytes, Aspergillus fumigatus, mainly saprophytic or potentially pathogenic fungi of the cutaneo-mucous flora . Minimal inhibitory concentrations on this antiseptic indicate a high susceptibility of the species tested, that could justify the enlargement of the indication of the drug to the complementary treatment of most cutaneous mycosis.

Mycopathologia, 1990 Sep, 111(3), 165 - 8
The effect of mycophenolic acid on the cell cycle of Candida albicans; Quinn CM et al.; Mycophenolic acid inhibited the growth of Candida albicans . Cultures exposed to a concentration of 8.4 micrograms ml-1 mycophenolic acid were found to exhibit cell cycle arrest with two or more buds . Nuclear staining revealed that these were nucleate implying a possible defect in cytokinesis . The results are discussed in relation to the possible mode of action of mycophenolic acid.

J Med Microbiol, 1990 Sep, 33(1), 43 - 9
The relationship between colonisation, secretor status and in-vitro adhesion of Candida albicans to buccal epithelial cells from diabetics; Darwazeh AM et al.; This study investigated whether oral candida infection in diabetics and adhesion of Candida albicans to buccal epithelial cells in vitro were related . Buccal cells from 50 patients with diabetes mellitus showed a significant increase in adhesion of C . albicans strain CDS 88 compared with those collected from 50 non-diabetic controls matched for age, sex and denture status . Oral candida carriage, candida infection and secretor status were also investigated in both groups . The frequency of carriage was increased, but not significantly, and there was a significantly higher incidence of candida infection in diabetic patients compared with controls . Diabetic patients who were non-secretors had a significantly increased frequency of oral candida carriage.

Microbiol Rev, 1990 Sep, 54(3), 226 - 41
Genetics of Candida albicans; Scherer S et al.; Candida albicans is among the most common fungal pathogens . Infections caused by C . albicans and other Candida species can be life threatening in individuals with impaired immune function . Genetic analysis of C . albicans pathogenesis is complicated by the diploid nature of the species and the absence of a known sexual cycle . Through a combination of parasexual techniques and molecular approaches, an effective genetic system has been developed . The close relationship of C . albicans to the more extensively studied Saccharomyces cerevisiae has been of great utility in the isolation of Candida genes and development of the C . albicans DNA transformation system . Molecular methods have been used for clarification of taxonomic relationships and more precise epidemiologic investigations . Analysis of the physical and genetic maps of C . albicans and the closely related Candida stellatoidea has provided much information on the highly fluid nature of the Candida genome . The genetic system is seeing increased application to biological questions such as drug resistance, virulence determinants, and the phenomenon of phenotypic variation . Although most molecular analysis to data has been with C . albicans, the same methodologies are proving highly effective with other Candida species.

Transplantation, 1990 Sep, 50(3), 506 - 10
Evaluation of amphotericin B-cyclosporine interaction in the rat; Langston JD et al.; Although a significant interaction between cyclosporine and amphotericin-B (AmpB) has been observed clinically, these findings have not been duplicated in animal studies . A total of 64 male albino rats were used in single- and multiple-dose experiments with AmpB and CsA in the absence or presence of systemic Candida infection . No significant differences in glomerular filtration rate were found in rats given single i.v . doses of AmpB 1 mg/kg compared with AmpB and CsA . Furthermore, rats given i.p . AmpB 1 mg/kg and CsA 10 mg/kg daily for 10 days showed no significant differences in GFR compared with animals given CsA alone . Morphology and CsA whole-blood pharmacokinetics were not different between groups administered single-dose CsA, AmpB, or the combination; similarities also existed with multiple-dose studies . In an attempt to mimic the clinical setting, 2 groups of rats were administered i.p . CsA 10 mg/kg/day for 10 days followed by inoculation of Candida albicans . After 48 hr, a single i.v . dose of AmpB 1.0 mg/kg was associated with a 33% decline in GFR compared with those given sterile water (P less than 0.05) . Systemic clearance of CsA was markedly reduced in candidiasis rats administered AmpB compared with controls given sterile water . A significant reduction in renal Candida colony-forming units was found in rats given CsA and AmpB compared with those administered CsA alone . These data suggest that the presence of systemic Candida highlights the interaction of CsA and AmpB in the rat model.

Infect Immun, 1990 Sep, 58(9), 2750 - 4
Tumor necrosis factor (TNF) is induced in mice by Candida albicans: role of TNF in fibrinogen increase; Riipi L et al.; One intraperitoneal dose of Candida albicans (10(8) CFU) caused a chronic (longer than 2 months), significant elevation of plasma fibrinogen levels (Clauss method) in mice of strain C3H/HeN . Even a small dose (10(6) CFU) resulted in a significant increase in fibrinogen level for 5 days following injection, whereas other blood parameters (leukocytes, erythrocytes, platelets, hematocrit, hemoglobin, blood urea nitrogen, aspartate aminotransferase, albumin, alkaline phosphatase, antithrombin III, glucose, calcium, and total protein) measured by standard methods were normal . Blood taken during this period was negative for C . albicans . The role of tumor necrosis factor (TNF) in C . albicans infections was investigated by measuring the fibrinogen response after the administration of C . albicans or recombinant mouse TNF-alpha . Both challenges resulted in an elevated fibrinogen level . When polyclonal antibodies to mouse TNF-alpha were given prior to challenge with C . albicans or mouse TNF-alpha, the fibrinogen increase was significantly inhibited . C . albicans injections were found to significantly elevate endogenous TNF levels in mice (enzyme-linked immunosorbent assay) . It was concluded that C . albicans induces TNF in the mouse . Furthermore, these data give evidence which supports a relationship between TNF and the fibrinogen increase induced by C . albicans.

Antimicrob Agents Chemother, 1990 Sep, 34(9), 1672 - 7
Effects of antiretroviral dideoxynucleosides on polymorphonuclear leukocyte function; Roilides E et al.; Dideoxynucleosides (zidovudine{AZT}, dideoxycytidine{ddC}, and dideoxyinosine{ddI}) are promising new agents for the management of human immunodeficiency virus type 1 (HIV-1) infections . In light of recent data demonstrating defects in the polymorphonuclear leukocyte (PMN) bactericidal activity of HIV-1-infected patients and since many chemotherapeutic agents affect PMN function, we examined their effects on the function of PMNs from both healthy and HIV-1-infected individuals in vitro . AZT (0.1 to 25 microM), ddC (0.01 to 1 microM), and ddI (0.2 to 50 microM) had no effect on viability, chemotaxis to N-fromylmethionyl leucyl phenylalanine, phagocytosis of Candida albicans or Staphylococcus aureus, or superoxide production following stimulation by N-formylmethionyl leucyl phenylalanine . Killing of C . albicans was not affected by AZT but was enhanced by 0.1 and 1 microM ddc (a 1 microM, killing was 26.0 +/- 2.02% compared with 17.0 +/- 0.73% for controls: P = 0.006) and 0.2 to 50 microM ddI (at 10 microM, killing was 25.0 +/- 0.68% compared with 17.8 +/- 0.91% for controls; P = 0.002) . Killing of S . aureus was unchanged by AZT and ddC but was significantly enhanced by ddI at 0.2 to 20 microM (at 2 microM, killing was 71.2 +/- 5.57% compared with 51.4 +/- 6.29% for controls; P = 0.0045) . In addition, the preexisting defective bactericidal capacity of PMNs from HIV-1-infected patients was enhanced by ddI (P less than 0.025) . Potential enhancement by these dideoxynucleosides of certain PMN functions of HIV-1-infected patients deserves further study.

Cell Immunol, 1990 Sep, 129(2), 271 - 87
Induction of LAK-like cells in the peritoneal cavity of mice by inactivated Candida albicans; Scaringi L et al.; We have investigated the effect of multiple administrations of inactivated Candida albicans (CA) cells on induction of non-MHC-restricted antitumor cytotoxic responses both in normal and congenitally athymic (nude) mice . Intraperitoneal inoculation of CD2F1 mice with five doses of 2 x 10(7) CA cells over a 2-week interval was associated with the induction of peritoneal exudate cells (PEC) that mediated natural killer cell activity . These cells, in contrast to those elicited by a single dose of CA, killed both NK-sensitive and NK-resistant tumor target cells in vitro . This broad-spectrum, antitumor cytotoxicity peaked 1 day after the last injection of CA, and decreased to control values within 6 (NK-resistant) or 14 (NK-sensitive target cells) days . Cytotoxicity could be recalled to a high level by a boosting injection of CA or a major mannoprotein-soluble antigen (MP) from the Candida cell wall, given 30 days after multiple CA treatment . Upon a 24-hr in vitro incubation, CA-induced peritoneal immunoeffectors lost their killing activity unless human recombinant interleukin-2 (rIL-2) was added to cultures . The non-MHC-restricted cytotoxic PEC activity induced by CA was mainly associated with nonadherent, nonphagocytic large granular lymphocytes (LGL) which exhibited the following phenotypes: (i) asialo GM1+, Lyt 2.2-, and partially Thy 1.2+ (effectors active against NK-sensitive targets) and (ii) asialo GM1+, Lyt 2.2-, and Thy 1.2+ (effectors active against NK-resistant targets) . Nude mice also responded to multiple CA inoculations by displaying high cytotoxic activity against NK-sensitive targets and significant cytotoxicity against NK-resistant targets . This cytotoxicity could be recalled on Day +30, and the cytotoxic effectors involved were highly sensitive to anti-asialo GM1 plus complement treatment . Overall, the results add further experimental evidence to the wide range of immunomodulatory properties possessed by C . albicans, and demonstrate that the majority of antitumor cytotoxic activity induced by fungal cells was due to lymphokine-activated killer (LAK)-like effectors.

Cesk Epidemiol Mikrobiol Imunol, 1990 Sep, 39(5), 294 - 302
{Serological identification of medically significant yeasts}; Tomsikova A et al.; The authors describe possibilities of serological identification of medically significant yeasts by means of agglutination with specific monofactorial sera . This method permits identification of different species within several minutes and has, as compared with laborious biochemical methods which take several days, considerable advantages . The authors examined 265 clinical isolates of yeasts by means of slide agglutination and 11 morphological and biochemical tests . Agreement between results of serological and conventional identifications was recorded in 98.5% of the tested strains . One of the advantages of serological assessment of yeasts is also the possibility of rapid differentation of serotypes of the very frequently occurring species Candida albicans.

J Antimicrob Chemother, 1990 Sep, 26(3), 399 - 409
Relation between the therapeutic efficacy of imipenem in an experimental infection in granulocytopenic mice and its effect on murine intestinal microbial ecology; van Ogtrop ML et al.; A study was performed to assess the effect of parenteral administration of imipenem on the intestinal microbial ecology of mice in relation to the therapeutic efficacy of the drug . The therapeutic effect of imipenem was assessed in a short-term experimental thigh muscle infection with Escherichia coli in irradiated mice . The maximum antibacterial effect of imipenem was approached at a single dose of 80 mg/kg . At this dose of imipenem the number of viable E . coli in the thigh muscle decreased from 9 x 10(6) to 4 x 10(5), whereas in untreated controls this number increased from 9 x 10(6) to 2 x 10(8) . Daily administration of a dose of 80 mg/kg imipenem caused significant changes in the intestinal flora of conventional mice, despite the low concentrations of the drug (about 1 mg/kg) found in the caecum 30 min after infection of this dose . These changes consisted of an increase in the number of E . coli and enterococci and a decrease in the number of Staphylococcus aureus in the faeces . Furthermore, at this dose of imipenem, the number of Candida albicans recovered from the faeces after oral contamination with this organism was increased . We conclude from these animal experiments that the use of imipenem in high doses causes ecological changes in the intestinal bacterial flora with the potential to promote colonization by candida.

Tokai J Exp Clin Med, 1990 Sep, 15(5), 395 - 9
Heat production due to intracellular killing activity; Hayatsu H et al.; Using Saccharomyces ceravisiae, Candida albicans and Stapylococcus aureus, heat production during phagocytosis was measured in U937 cells which are capable of differentiating to monocytic phagocytes . No increase in heat production of non-differentiated U937 was observed since they were not phagocytic cells . However after differentiation to monocytic phagocytes by lymphokine, U937 cells produced a remarkable amount of heat during phagocytosis . Although Ehrlich ascites tumor cells sensitized with antibody were capable of engulfing S . aureus, no increase in heat nor in superoxide anion production during phagocytosis was detected . It was also found that no heat increase occurred in neutrophils from a patient with chronic granulomatous disease (CGD) . It can thus be concluded that the heat production during phagocytosis is due to the intercellular killing process of phagocytic cells.

Infect Immun, 1990 Sep, 58(9), 2869 - 74
Altered hepatic clearance and killing of Candida albicans in the isolated perfused mouse liver model; Sawyer RT et al.; The adherence of Candida albicans was studied in situ by using the perfused mouse liver model . After exhaustive washing, 10(6) C . albicans were infused into mouse livers . At the time of recovery, 62 +/- 5% (mean +/- standard error of the mean) of the infused C . albicans were recovered from the liver and 14 +/- 3% were recovered from the effluent for a total recovery of 76 +/- 4% . This indicates that 86 +/- 3% of the original inoculum was trapped by the liver and that 24 +/- 4% was killed within the liver . Chemical pretreatment of C . albicans with 8 M urea, 12 mM dithiothreitol, 2% beta-mercaptoethanol, 1% sodium dodecyl sulfate, 10% Triton X-100, or 3 M potassium chloride or enzyme pretreatment with alpha-mannosidase, alpha-chymotrypsin, subtilisin, beta-N-acetyl-glucosaminidase, pronase, trypsin, papain, or lipase did not alter adherence of C . albicans to hepatic tissue . By contrast, pepsin pretreatment significantly decreased hepatic trapping . Simultaneous perfusion with either 100 mg of C . albicans glycoprotein per liter or 100 mg of C . albicans mannan per liter also decreased trapping . Furthermore, both substances eluted previously trapped C . albicans from hepatic tissue . Chemical pretreatment with 8 M urea, 12 mM dithiothreitol, or 3 M KCI or enzymatic pretreatment with alpha-mannosidase, subtilisin, alpha-chymotrypsin, or papain increased killing of C . albicans three- to fivefold within hepatic tissue . The data suggest that mannose-containing structures on the surface of C . albicans, for example . mannans or glucomannoproteins, mediate adherence of C . albicans within the liver . Indirectly, chemical and enzymatic pretreatment renders C . albicans more susceptible to hepatic killing.

Mycoses, 1990 Sep-Oct, 33(9-10), 435 - 40
Fluconazole in the treatment of oropharyngeal candidosis in HIV-positive patients; Just-Nubling G et al.; 106 HIV-positive patients with 129 episodes of oropharyngeal Candida infection were treated with fluconazole (50-300 mg/d) . Treatment lasted from 4 to 23 days . The majority of patients were in more advanced stages of HIV infection (82% AIDS cases) . Therapy with fluconazole led to complete healing or improvement of clinical symptoms in 93% of all treatment courses . However, according to cultural findings, an elimination or recession of pathogens was achieved in only 70% of cases . Cultural monitoring showed a slow reduction of pathogens, as opposed to a fairly rapid clinical improvement . Candida albicans was the most frequently isolated Candida species (n = 128); the most selected Candida species during treatment were C . glabrata, C . krusei, and C . inconspicua . It is remarkable that C . glabrata, a low-grade pathogen, caused enanthema in 2 patients and a typical oral thrush in 1 patient . Fluconazole was well-tolerated, and apart from mild gastro-intestinal symptoms in 1 patient, no severe side effects were observed.

Mycoses, 1990 Sep-Oct, 33(9-10), 431 - 4
Oral carriage of yeasts in two villages in Papua New Guinea; Clayton YM et al.; Oral swabs were taken from 194 subjects in two villages in Papua New Guinea . Yeasts were isolated from 103 (53.1%) individuals of which 41 (21.1%) were Candida albicans . A wide variety of other yeasts were also identified.

Brain Behav Immun, 1990 Sep, 4(3), 180 - 8
Evaluation of immunologic assays to determine the effects of differential housing on immune reactivity; Salvin SB et al.; The mechanism is being investigated to determine specifically how an environmental variation such as differential housing can influence the multiple components of the host defense mechanism . Male C3H/HeJ mice were housed either one or five per cage . Cells and sera from these mice were analyzed and compared by several immunologic techniques to determine in which cells or tissues the effect of differential housing was most pronounced . The individually housed mice (a) had a greater capacity to phagocytose dead cells of Candida albicans . (b) had spleens that produced more macrophage colony stimulating factor (M-CSF) . (c) were more responsive to M-CSF, (d) had peritoneal macrophages that released greater quantities of interleukin-1 in vitro into the surrounding medium and that had a greater capacity to migrate toward a chemotactic stimulus, and (e) had higher titers of IgM hemagglutination antibody to sheep erythrocytes . Differential housing of mice may therefore be a highly important modulator and indicator of the nature and extent of an animal's immunologic response to an environmental stimulus.

Arzneimittelforschung, 1990 Sep, 40(9), 1068 - 72
{Immunomodulating effect of lysed immunoactive fractions of selected Escherichia coli strains on the macrophage system . An in vitro study}; Hockertz S; The immunomodulator Uro-Vaxom (an immunoactive fraction of E . coli, FEC) is a therapeutic agent used to control bacterial infections . FEC was applied to macrophages of C57BL/6 mice to investigate the in vitro activation of these cells of the unspecific immune system . Experiments were designed to test the secretory, immuno-regulatory and cytotoxic function of macrophages after application of FEC . As presented here, production of Interleukin-6 and tumor-necrosis-factor were significantly and dose-dependent way increased, whereas it was not possible to induce a secretion of Interleukin-1 . In addition, FEC activated macrophages kill Leishmania donovani promastigotes, Candida albicans and Staphylococcus aureus . In comparison to a pressed echinaceae-preparation, FEC activated mouse macrophages secrete Interleukin-6 and tumor-necrosis-factor and kill protozoa, fungi and bacteria, with higher efficiency.

Arzneimittelforschung, 1990 Sep, 40(9), 1044 - 7
Interaction of fluconazole and human phagocytic cells . Uptake of the antifungal agent and its effects on the survival of ingested fungi in phagocytes; Wildfeuer A et al.; 3H-labelled fluconazole (CAS 86386-73-4) very rapidly penetrated into polymorphonuclear leucocytes (PMNLs) and macrophages (monocytes) isolated from volunteers . The concentration of the antimycotic in the PMNLs was about 28% and in the macrophages even 63% above that in the extracellular medium . At the concentrations examined (5, 10 and 20 micrograms/ml) fluconazole damaged cells of Candida albicans which had been phagocytized by PMNLs or macrophages . There is an evident synergism between therapeutically attainable concentrations of fluconazole and phagocytic cells and this militates against the intracellular survival of the fungus.

Infect Immun, 1990 Sep, 58(9), 2804 - 8
Evidence that Candida stellatoidea type II is a mutant of Candida albicans that does not express sucrose-inhibitable alpha-glucosidase; Kwon-Chung KJ et al.; Candida stellatoidea is classically distinguished from C . albicans by the ability of the latter species to assimilate sucrose . We show here that sucrose-positive revertants of C . stellatoidea type II are readily isolated and that C . stellatoidea type II strains probably resulted from a mutation in the sucrase gene of C . albicans . The revertants were not laboratory contaminants, as determined by restriction fragment length polymorphism analysis and retention of an auxotrophic marker . The reversion of three tested strains was accompanied by 16 to 110-fold increases in expression of a sucrase/alpha-glucosidase but not an invertase, with a Km for sucrose of about 1 mM . The enzyme activity was assayable in intact cells . The drastically increased expression of such an enzyme would allow extracellular sucrose hydrolysis and assimilation of the monosaccharide products.

Zhonghua Kou Qiang Yi Xue Za Zhi, 1990 Sep, 25(5), 294 - 6, 318
{The laboratory examination of Candida albicans}; Wang BY; This study compares the laboratory methods in detecting candidas causing oral candidiasis and suggests that smear method is the main one . PAS stain is the best for diagnosis, and the potassium hydroxide method is the easiest and quickest in handling . As to those uncertained by smear method, culture should be done . For those positive on Sabouraud's medium, the germ tube test should be performed and positive results can be regarded as candida albicans . If negative the chlamydospore production as well as the carbohydrate fermentation and assimilation should be done.

J Immunol Methods, 1990 Aug 7, 131(2), 269 - 75
A fast and easy method to determine the production of reactive oxygen intermediates by human and murine phagocytes using dihydrorhodamine 123; Emmendorffer A et al.; Analysis of the functional activity of phagocytes is of great importance in the differential diagnosis of patients with recurrent bacterial infections . Here we describe a method to determine the production of reactive oxygen intermediates (ROI) by microcytofluorometry using dihydrorhodamine 123, a derivative of rhodamine 123 . Using this method the ROI production of erythrocyte-depleted whole blood samples can be measured without further time-consuming purification steps . Possible harmful manipulation of the isolated cells can also be avoided and highly reproducible and significant results are obtained in the minimum of time . This assay provides a very sensitive alternative to the clinically used NBT test in the diagnosis of patients with chronic granulomatous disease (CGD) . Moreover, the analysis of oxygen-dependent effector functions of murine effector cells and cell lines may be important in investigating resistance to certain microbes (e.g., Candida albicans, Staphylococcus aureus or different protozoa such as Toxoplasma gondii or Leishmania species).

J Pediatr Surg, 1990 Aug, 25(8), 878 - 80
The diagnosis of pneumonia in the immunocompromised child: use of bronchoalveolar lavage; Winthrop AL et al.; Between January 1987 and December 1988, 26 immunocompromised children (aged 15 months to 17 years) underwent bronchoalveolar lavage (BAL) for evaluation of pneumonia (chemotherapy for malignancy, 12; orthotopic liver transplantation, 9; other hematologic disease, 5) . Bilateral diffuse pulmonary disease was present in 25 children . All were receiving broad spectrum antibiotics . In addition, five were receiving antiviral therapy and two were receiving antifungal therapy . Sixteen patients underwent rigid and 10 underwent flexible bronchoscopy . Two lavages of 10 to 20 mL of normal saline were obtained from involved subsegmental bronchi of both lungs in each patient . Second wash samples from each lung were sent for bacterial and viral cultures, silver staining for pneumocystis, and direct electronmicroscopy analysis for viral particles . Samples were considered satisfactory if they contained an abundance of alveolar macrophages and only small numbers of upper respiratory tract epithelial cells . Alveolar macrophages were present in 21 (81%) of the BAL samples . A specific infectious agent was identified in 15 of these patients (cytomegalovirus {CMV}, 6; Pneumocystis carinii, 4; gram-positive cocci, 3; Candida albicans, 2), and therapy was modified in 12 . In the five patients in whom BAL samples were contaminated with upper respiratory tract cells no infectious agents were isolated . Because of continued clinical deterioration, open-lung biopsies were performed in three patients in whom BAL had identified CMV and in three patients in whom no organisms had been obtained . Lung biopsies did not identify any new infectious agents, although in the latter group specific histological diagnosis of a noninfectious process was made (hemorrhagic infarct, bronchiolitis obliterans, and lymphoma).(ABSTRACT TRUNCATED AT 250 WORDS)

J Clin Microbiol, 1990 Aug, 28(8), 1828 - 41
Evaluation of a murine model of hepatic candidiasis; Cole GT et al.; A murine model of focal hepatic candidiasis which we suggest simulates certain conditions of this clinical variant of systemic candidiasis in leukemic patients is described . We have shown that outbred mice inoculated with Candida albicans by the oral-intragastric route as infants (6 days old) and then immunocompromised by cyclophosphamide and cortisone acetate treatment 2 weeks later demonstrate systemic spread of the opportunistic pathogen to the liver, lungs, spleen, and kidneys . Treatment with the immunosuppressive drugs cyclophosphamide and cortisone acetate resulted in alteration of the normal integrity of the mucosal epithelium of the gut as well as in granulocytopenia . Approximately 55% of the animals with C . albicans infections in the liver demonstrated hepatic abscesses . After these same infected, immunocompromised animals were treated with suboptimal dosages of antifungal agents (cilofungin or amphotericin B), either by intraperitoneal or subcutaneous (s.c.) routes, persistent hepatic abscesses were fewer in number and delimited by a distinct outer layer of host tissue but still contained large numbers of the viable pathogen . Blood cell counts indicated that these antifungal drug-treated animals had reestablished approximately the same number of leukocytes per microliter of blood as estimated prior to the immunocompromising drug treatment . Similar conditions in leukemic patients who were in remission and who were undergoing antifungal drug therapy for systemic candidiasis have been reported . Clearance of hepatic infections in mice was accomplished by using appropriate concentrations of amphotericin B administered by daily intraperitoneal or s.c . injection for 5 to 7 days or cilofungin by continuous s.c . infusion for 7 days . However, systemic antifungal therapy did not significantly reduce numbers of C . albicans cells in the stomach and esophagus . Persistent foci of gastrointestinal colonization by C . albicans, especially in the region of the cardial-atrium fold of the stomach of these mice, are reservoirs of the opportunistic pathogen from which reinfection may occur, leading to relapse of systemic candidiasis.

Agents Actions, 1990 Aug, 31(1-2), 86 - 95
Phagocytic function and antibody-dependent cellular cytotoxicity of human neutrophils in the presence of N-formimidoyl thienamycin; Rodriguez AB et al.; The efficacy of an antibiotic in the treatment of bacterial infections depends upon the interactions of the drug, bacteria and phagocytes . We have studied "in vitro" the effect of N-formimidoyl thienamycin (Imipenem), a novel beta-lactamic antibiotic, on the phagocytic function and antibody-dependent cellular cytotoxicity of human neutrophil leukocytes . The incubation of these cells with 50 micrograms/ml of Imipenem similar to the therapeutic levels reached in plasma results in an increase of their adherence capacity to nylon fiber and to substrate, induced mobility or chemotaxis, opsonization, phagocytosis of Candida albicans (with serum, with decomplementarized serum and without serum) and latex beads, candidicidal power and the capacity of NBT reduction . Imipenem at this dose also presents chemoattractant power for neutrophils and enhances the antibody-dependent cellular cytotoxicity (ADCC).

J Gen Microbiol, 1990 Aug, 136 ( Pt 8), 1475 - 81
Uptake of pyrimidines and their derivatives into Candida glabrata and Candida albicans; Fasoli MO et al.; The uptake of pyrimidines and their derivatives into Candida glabrata and Candida albicans was measured using a novel technique in which the cells were rapidly separated from their suspending medium by centrifugation through a layer of an inert oil . The uptake of {14C}cytosine was linear for 30 s for all concentrations of pyrimidine tested . In C . glabrata but not C . albicans cytosine transport was mediated by both a high affinity (Km 0.8 +/- 0.1 microM), low capacity {V 40 +/- 4 pmol (microliters cell water)-1 s-1} and a low affinity {Km 240 +/- 35 microM}, high capacity system {V 770 +/- 170 pmol (microliters cell water)-1 s-1} . The cytosine permease in C . glabrata was specific for cytosine and 5-fluorocytosine . In C . albicans there was only one cytosine transport system {Km 2.4 +/- 0.3 microM; V 50 +/- 4 pmol (microliters cell water)-1 s-1}; this system also transported adenine, guanine and hypoxanthine . Differences in nucleoside transport were also observed for C . glabrata and C . albicans, with the uridine permease in C . glabrata transporting only uridine and 5-fluorouridine whereas cytidine and adenosine were also transported by the uridine permease in C . albicans . Studies on the effect of nucleoside analogues on uridine transport in C . glabrata demonstrated the importance of the sugar moiety in determining the specificity of transport, with a hydroxyl residue on C-2 being apparently essential for transport.

Tohoku J Exp Med, 1990 Aug, 161(4), 273 - 81
Liposome-encapsulated amphotericin B in the treatment of experimental murine candidiasis; Miyazaki T et al.; The efficacy of liposome-encapsulated amphotericin B in treating experimental murine candidiasis was compared with that of the commercially available amphotericin B (Fungizone) . The LD50 of liposomal amphotericin B in ddY mice exceeded 10.0 mg/kg while that of Fungizone was 3.0 mg/kg . Experimental candidiasis was induced by injecting a clinical isolate of Candida albicans strain 0925-107-01, through the tail vein . With the injection of 1.7 x 10(6) colony forming units, the number of colonies in the kidneys remained between 2.1 x 10(5) and 1.2 x 10(6), whereas the number of colonies in blood, liver, spleen, lungs and heart decreased rapidly . Histological examination revealed severe pyelonephritis with fungal infiltration and a mild invasion of the heart, lungs, liver and spleen . The survival rate of mice with experimental candidiasis treated with Fungizone at a dose of 0.8 mg/kg was 50% (the maximum tolerated dose without acute lethality), whereas all mice treated with the liposomal amphotericin B at a dose of 5.0 mg/kg were alive even 42 days after the inoculation (p less than 0.01) . Using liposome as a carrier for amphotericin B decreased this drug's systemic toxicity making it possible to administer doses higher than feasible with the commercial preparation and thus obtaining better therapeutic efficacy.

Pathol Res Pract, 1990 Aug, 186(4), 527 - 34
What's new in the mechanisms of host resistance to Candida albicans infection?
Ashman RB, Papadimitriou JM.
Despite extensive investigation, the mechanisms of host resistance against C . albicans infection remain poorly understood . Granulocytes and macrophages are the major effector cell types; however, their intrinsic candidacidal activity is rather limited, and its full expression requires augmentation by components of the T cell-initiated lymphokine cascade . Consequently, susceptibility to recurrent mucocutaneous infections may be associated with aberrant T cell function . In contrast, protection from systemic infection appears to be mediated by candida-specific antibodies.

Acta Paediatr Scand, 1990 Aug-Sep, 79(8-9), 876 - 9
Necrotizing bowel disease with candida peritonitis following severe neonatal hypothermia; Kaplan M et al.; Peritonitis due to Candida albicans is rare in the newborn infant . Three low birthweight, extremely ill premature infants who were severely hypothermic at the time of admission developed perforation of the gastrointestinal tract . C . albicans was cultured from the peritoneal fluid in each case . In view of the rareness of C . albicans peritonitis in newborns, this cluster of infants suggests a relationship between severe neonatal hypothermia, and bowel perforation with peritonitis due to this fungus.

Zh Mikrobiol Epidemiol Immunobiol, 1990 Aug, (8), 103 - 7
{Delayed hypersensitivity to Candida albicans}; Frolova EV et al.; Conditions and factors influencing the formation of delayed hypersensitivity (DH) to yeast-like fungi of the species C . albicans under experimental conditions have been studied . The intensity of this reaction has been found to depend on the dose and method used for infecting mice, the time of the test and the qualitative state of fungal cells . As the result of this study, the infectious model of DH to C . albicans has been proposed . This model may be used for the study of the influence of different exogenous and endogenous factors of cell-mediated immune response to candidiasis.

J Oral Pathol Med, 1990 Aug, 19(7), 326 - 9
In vivo effects of Candida albicans products on rat oral epithelium; Reed MF et al.; Candida albicans has been associated with epithelial hyperplasia in some diseases of oral mucosa and skin but its etiologic role in these lesions is poorly understood . To test its ability to induce epithelial proliferation, the invasive hyphal form was cultured for 5 h and 23 h in chemically defined medium and yeast-free culture supernatants were injected below the buccal epithelium of young adult Sprague Dawley rats . The mitotic activity was assessed using the metaphase arrest technique 11 h and 31 h after supernatant injection . There was a significant increase in epithelial mitotic activity 31 h after injection with 5 h culture supernatants compared to control media indicating that the supernatants have an effect on epithelial cells, possibly by direct action on them.

J Pharm Sci, 1990 Aug, 79(8), 725 - 31
Computer automated structure evaluation of antifungal 1-vinylimidazoles, 1,2-disubstituted propenones, and azolylpropanolones; Macina OT et al.; The Computer Automated Structure Evaluation (CASE) program has been applied to a series of 1-vinylimidazoles, 1,2-disubstituted propenones, and azolylpropanolones exhibiting in vitro antifungal properties . Relevant molecular fragments were obtained for activity against the fungal strains Candida albicans, Aspergillus fumigatus, and Trichophyton asteroides . Fragments were utilized as descriptors to derive quantitative structure-activity relationships (QSAR) within each respective biological endpoint . A high degree of correlation was observed between fragments derived from C . albicans and A . fumigatus . The relevant activating and inactivating fragments from each of the respective biological endpoints analyzed are discussed.

Tierarztl Prax, 1990 Aug, 18(4), 339 - 41
{Disseminated candidiasis in a calf . Case report}; Roth M et al.; The pathological-anatomical and histological examinations of different organs from a calf that died at the age of 9 weeks indicated a disseminated candidiasis . Candida albicans was isolated from brain, lung, liver, spleen, kidney, intestinal lymph nodes and small intestinal contents . The antibiotics administered to the calf by the owner probably initiated the disseminated candidiasis.

Zentralbl Bakteriol, 1990 Aug, 273(3), 332 - 43
Comparative pathogenicity of a wild-type strain and respiratory mutants of Candida albicans in mice; Aoki S et al.; The pathogenicity of a parent wild-type strain and three respiratory mutants of Candida albicans was examined in intravenously infected mice . The wild-type strain K grew well in the kidney and caused severe candidosis, and the 21-day LD50 value was 7.2 x 10(6) cells/mouse . A mutant with a low rate of respiration (KRD-8) whose growth rate in vitro was somewhat lower than that of the wild type, produced germ tubes in vitro to the same extent as the wild-type strain and was associated with mortality rates similar to those of the wild-type strain . Two respiration-deficient (petite) mutants (KRD-19 and KRD-51), whose growth rates in vitro were far lower than that of the wild-type strain, could neither colonize the kidney nor cause fatal infection, even at a dose of 10(8) cells/mouse . Formation of germ tubes and hyphal growth in vitro of the petite mutants were less extensive than those of the wild-type strain or KRD-8 . Extracellular proteinase was produced at pH 3.5 by the wild-type strain and by KRD-8 but not by the petite mutants . From these results, it is most likely that the nonlethality of infection by the petite mutants in mice results primarily from the low capacity of growth of these mutants, even though the inability of the petite mutants to produce extracellular proteinase may be also related to some extent to their avirulence.

J Clin Microbiol, 1990 Aug, 28(8), 1854 - 7
Multivariate analyses of cellular carbohydrates and fatty acids of Candida albicans, Torulopsis glabrata, and Saccharomyces cerevisiae; Brondz I et al.; Quantitative data of major cellular carbohydrates distinguished Candida albicans or Torulopsis glabrata from Saccharomyces cerevisiae but not C . albicans from T . glabrata . Multivariate analyses of both carbohydrate and fatty acid variables (I . Brondz, I . Olsen, and M . Sjostrom, J . Clin . Microbiol . 27:2815-2819, 1989), however, differentiated all three species.

J Bacteriol, 1990 Aug, 172(8), 4407 - 14
Phospholipid biosynthesis in Candida albicans: regulation by the precursors inositol and choline; Klig LS et al.; Phospholipid metabolism in the pathogenic fungus Candida albicans was examined . The phospholipid biosynthetic pathways of C . albicans were elucidated and were shown to be similar to those of Saccharomyces cerevisiae . However, marked differences were seen between these two fungi in the regulation of the pathways in response to exogenously provided precursors inositol and choline . In S . cerevisiae, the biosynthesis of phosphatidylcholine via methylation of phosphatidylethanolamine appears to be regulated in response to inositol and choline; provision of choline alone does not repress the activity of this pathway (G . M . Carman and S . A . Henry, Annu . Rev . Biochem . 58:636-669, 1989) . The same pathway in C . albicans responds to the exogenous provision of choline . Possible explanations for the observed differences in regulation are discussed.

J Infect Dis, 1990 Aug, 162(2), 519 - 22
Elevated antibody levels to mycobacterial 65-kDa stress protein in patients with superficial candidiasis; Ivanyi L et al.; Antibody levels to the mycobacterial 65-kDa stress protein (mSP65) were determined by ELISA in sera from patients with chronic atrophic oral candidiasis, vulvovaginal candidiasis, Candida albicans-infected or noninfected oral lichen planus, or recurrent aphthous ulceration and from subjects with clinically healthy oral mucosa . The results showed significantly elevated anti-mSP65 antibody levels in patients with oral or vulvovaginal candidiasis and in patients with Candida-infected lesions of lichen planus when compared with patients with noninfected lichen planus or recurrent oral ulceration and with matched healthy controls (P less than .001) . Immunoblot analysis showed that the rabbit antiserum that strongly bound to mSP65 cross-reacted only weakly with a homologous band of a soluble C . albicans extract . Moreover, the binding of antibodies from patients with candidiasis to the mSP65 antigen was not inhibited in the presence of Candida extract . In view of the poor serologic cross-reactivity, it seems plausible that the recall stimulation of anti-mSP65-producing B cells could be induced by helper T cells that cross-react with the structurally homologous protein of C . albicans.

Infect Immun, 1990 Aug, 58(8), 2696 - 8
Comparison of candidacidal and candidastatic activities of human neutrophils; Sohnle PG et al.; Disruption of neutrophils causes the release of a cytoplasmic protein which can inhibit the growth of Candida albicans without killing the organisms . The present study was undertaken with a combined system in which candidacidal and candidastatic activities of human neutrophils could be compared . In this system it was found that disruption of either half or all of the neutrophils in the samples markedly improved the ability of the cells to handle an inoculum of Candida yeast cells over a 48-h period, even though the disrupted cells had primarily candidastatic activity, with very little candidacidal activity.

Am J Pathol, 1990 Aug, 137(2), 353 - 67
Cultured Reed-Sternberg cells HDLM-1 and KM-H2 can be induced to become histiocytelike cells . H-RS cells are not derived from lymphocytes; Hsu SM et al.; Two Hodgkin's Reed-Sternberg cell (H-RS) lines, HDLM-1 and KM-H2, have phenotypes and functional properties very similar to those of H-RS cells in tissues . These two types of cells were induced to differentiate with a combination of phorbol ester, retinoic acid, and extracellular matrix . The induced cells displayed the morphology of histiocytes or histiocytelike cells, with a small, round or oval, eccentric nucleus and abundant cytoplasm . In ultrastructural studies, many cytoplasmic projections and rugae were observed . These induced cells exhibited abundant cytoplasmic lysosomal enzymes, such as esterase, acid phosphatase, alpha 1-antitrypsin, or lysozyme . The histiocytic nature of these induced cells was further confirmed by the increased expression of many monocyte/histiocyte markers, including CD11b, CD11c, CD13, CD14, CD15, CD33, CD68, Mac387, and 1E9 . In functional tests, the induced cells were shown to produce interleukin-1, tumor necrosis factor, macrophage colony-stimulating factor, and/or prostaglandin E2 . Phagocytosis was detected in less than 5% to 10% of the cells when Candida albicans was added to cultures . The results strongly suggest that H-RS cells are related to cells of histiocyte lineage.

Z Hautkr, 1990 Aug, 65(8), 717 - 24
{Effect of phototoxic substances on simple biological systems . I . Standardizing the method with furocoumarins}; Schlacke KH et al.; As a basis for the investigation of new substances in respect of their photosensitization effects, we established and standardized 3 microbiological test systems, which enabled us to do without animal experiments . Using several furocumarines and various sources of light, we performed a comparative study on the eukaryotes, Chlamydomonas reinhardii (CR) and Candida albicans, and the prokaryote, Bacillus subtilis . We found that, if different light qualities were employed, our test systems also allowed a comparison of different substances by means of half-quantitative evaluation of the inhibiting areolas, which appear after exposure . With regard to the furocumarines, 8- and 5-methoxypsoralene (MOP) had the strongest photosensitizing effect under all test conditions . The remaining furocumarines showed decreasing effectiveness from psoralene to trimethylpsoralene (TMP) and imperatorine; psoralene, however, was slightly more effective in CR than 5-MOP . With the exception of CR, TMP had a stronger effect on the micro-organisms than imperatorine.

Oral Microbiol Immunol, 1990 Aug, 5(4), 226 - 32
Parameters affecting the inhibition of Candida albicans GDH 2023 and GRI 2773 blastospore viability by purified synthetic salivary histidine-rich polypeptides; Santarpia RP 3rd et al.; Purified synthetic salivary histidine-rich polypeptides, HRPs 2, 3, 4, 5, and 6, were observed to inhibit Candida albicans blastospore viability at yeast cell concentrations ranging from 10(2) to greater than 10(6) colony forming units per ml . Among the HRPs, HRP-4 was the best inhibitor with significant killing activity noted at a peptide concentration of 0.5 microgram per ml . Antifungal potency under growth conditions was observed to be dependent upon pH . In contrast, killing did not vary throughout the pH range tested under non-growth conditions . Electron microscopy results demonstrated HRP damage at pH 5 which appeared to be initiated at the membrane . At pH 7.4, micrographs revealed clear evidence of intracellular destruction suggesting more extensive damage at neutral as compared to acidic pH . These results suggest that within the changing realm of the oral cavity, the HRPs would be expected to be potent killers of C . albicans.

J Infect Dis, 1990 Aug, 162(2), 513 - 8
Candida albicans in patients with the acquired immunodeficiency syndrome: absence of a novel of hypervirulent strain; Whelan WL et al.; To determine whether Candida albicans in patients with AIDS represents a unique strain, C . albicans isolated from 24 patients with AIDS was compared with Candida isolated from 23 healthy adults . Resistance to 5-fluorocytosine, synthesis of amino acids and nucleotides, sugar use, and enzyme activity patterns were similar among isolates from the two groups . Molecular analysis revealed similar banding patterns of EcoRI restriction fragments of DNA between 2.5-3 and 6-7 kb . In addition, the frequency of a dimorphic 3.7-versus 4.2-kb band, identified by agarose gel electrophoresis and by probing Southern transfers of EcoRI digests with a cloned fragment of C . albicans DNA encoding 25S ribosomal RNA, was not significantly different between the AIDS-derived and control C . albicans . C . albicans isolated at different time points in the course of disease and from different sites in individual patients showed identical DNA fingerprints . The similarity in isolates of C . albicans that cause disease in AIDS patients and those present in healthy subjects suggests that the candidiasis associated with AIDS is not due to the presence of a unique or particularly virulent strain but is likely the consequence of a defect in host defense mechanisms.

Int J Oral Maxillofac Surg, 1990 Aug, 19(4), 212 - 5
Influence of skin graft pathology on residual ridge reduction after mandibular vestibuloplasty . A 5-year clinical and radiological follow-up study; Hillerup S et al.; The present study is a 5-year clinical and radiographic follow-up of 51 patients who had undergone a combined vestibuloplasty with a split skin graft and lowering of the floor of the mouth . Our purpose was to examine the effect of clinically evident graft pathology on the residual ridge reduction . The clinical records of the graft condition were classified into: healthy graft, partial loss of keratinization, and total loss of keratinization . The residual ridge reduction was monitored by ridge height measurements at different locations, and by the symphyseal and mandibular body areas . Patients with clinical signs of graft pathology (reddening, loss of keratinization) suffered a significantly more severe residual ridge reduction than those with a healthy skin graft (p less than 0.01) . Subsequent findings including smear tests showing Candida albicans hyphae, and improvement of graft condition after antimycotic therapy, indicated that the graft pathology observed is a candidiasis.

Fortschr Med, 1990 Jul 20, 108(21), 420 - 4
{The development of an aerobic intestinal microflora in newborn infants}; Sonnenborn U et al.; The microbial colonization of the intestinal tract was studied in 60 newborn babies from three hospitals, with special regard to the typical hospital "problem" strains . Escherichia coli was the predominant initial colonizing species . Opportunistic pathogens were repeatedly detected . Some 30% of E . coli strains showed beta-hemolysis . Distinct differences between the three clinics were noted with respect to the detection frequency of the species isolated, hemolytic bacteria, the predominating E . coli strains, the occurrence of Candida albicans, and the time course of colonization of the gut by E coli . The microbial environment of the respective neonatal unit has a great influence on the initial intestinal colonization by aerobic microorganisms.

Pol Tyg Lek, 1990 Jul 16-30, 45(29-31), 620 - 4
{Three month treatment with budesonide in patients with corticoid dependent bronchial asthma--personal experience}; Frank-Piskorska A et al.; The experiment aimed at evaluating a three-month therapy of asthmatic patients with budesonide inhalations . The study involved 32 patients with long-lasting bronchial asthma depended on steroids . Therapy with budesonide (Pulmicort Astra) in a mean daily dose 1.6 mg enabled withdrawal of depot steroids and inhalation treatment only . In patients receiving prednisone in a mean daily dose 5.0 +/- 4.8 mg, budesonide therapy enabled a reduction of the oral dose by 50 percent . A significant improvement in the psychophysical status of patients has been noted despite a lack of significant differences in the results of lung functioning tests . Adverse reactions such as relaxation, insufficiency of the vocal cords at phonation and hoarseness were seen in 20 percent of patients, and in one of them required cessation of the drug . An increase in the number of Candida albicans colonies in throat swabs (over 20 colonies per plate) was seen in 7 treated patients but clinical symptoms which required an additional treatment were noted only in 1 patient.

J Antibiot (Tokyo), 1990 Jul, 43(7), 771 - 7
New antifungal antibiotics, pradimicins D and E . Glycine analogs of pradimicins A and C; Sawada Y et al.; New antifungal antibiotics pradimicins D and E were isolated from the culture filtrates of Actinomadura hibisca P157-2 (ATCC 53557) and its mutant A2660 (ATCC 53762) . The structure of pradimicin D is N-{{(5S,6S)-5-O-{4,6-dideoxy-4-(methylamino)-3-O-(beta-D- xylopyranosyl)-beta-D-galactopyranosyl}-5,6,8,13-tetrahydro-1,6,9,14- tetrahydroxy-11-methoxy-3-methyl-8,13-dioxobenzo{a}naphthacen++ +-2-yl} carbonyl}glycine, based on spectral analyses compared to pradimicin A . Pradimicin E is the des-N-methyl analog of pradimicin D . Pradimicins D and E were equal in activity to pradimicin A in vitro against a variety of fungi and in vivo against Candida albicans A9540 in mice.

Arch Ophthalmol, 1990 Jul, 108(7), 1006 - 8
Ocular uptake of fluconazole following oral administration; O'Day DM et al.; The ocular penetration and distribution of oral fluconazole was studied in Dutch-belted rabbits . Measured by high-pressure liquid chromatography, fluconazole readily penetrated all ocular tissues and fluids . No difference was observed between the levels obtained in phakic and aphakic eyes . Four hours after a single oral dose of 20 mg/kg, the mean levels and SEs were as follows: cornea, 13.3 +/- 1.4 micrograms/g; aqueous, 7.4 +/- 0.3 mg/L; vitreous, 9.8 +/- 0.9 mg/L; and choroid/retina, 5.2 +/- 0.4 micrograms/g . These levels were approximately twice those obtained with a 10-mg/kg dose . The corneal concentrations correlated highly with serum levels (r = .89) . A steady accumulation in both normal corneas and corneas infected with Candida albicans was noted when 17.5 mg/kg of fluconazole was administered twice daily over a 5-day period . Drug levels did not increase in the cornea when fluconazole was administered as a single daily dose of 35 mg/kg . In view of its excellent ocular pharmacokinetic profile, fluconazole merits further attention as an orally administered agent for ocular fungal infections.

J Infect Dis, 1990 Jul, 162(1), 211 - 4
Enhancement of the treatment of experimental candidiasis with vascular decongestants; Luke DR et al.; The mechanism of amphotericin B (AmB) nephrotoxicity may be related to changes in vascular flow within the kidney, resulting in significant decreases in glomerular filtration rate and tubular integrity . The toxic and antifungal effects of AmB with and without the vascular decongestants pentoxifylline (PTX) and a methylxanthine analog, HWA-138, were compared in the murine model of candidiasis . At 48 h after inoculation with Candida albicans, half of the rats received a single intravenous 0.8 mg/kg dose of AmB whereas the others were administered sterile water . After 1 h, rats were randomized to receive three doses of 45 mg/kg PTX intraperitoneally, 5 mg/kg HWA-138 intravenously, or saline every 12 h . Renal function and Candida cell counts were estimated 24 h after AmB administration . Mean inulin clearances were significantly greater in rats coadministered AmB and PTX or HWA-138 than in AmB controls . Candida counts in kidneys of rats administered HWA-138 were similar independent of AmB therapy and markedly reduced compared with other groups . Whereas both vascular decongestants prevented drug-associated renal toxicity, the coadministration of AmB with HWA-138 resulted in a profound antifungal effect.

Trop Geogr Med, 1990 Jul, 42(3), 238 - 40
Relation between the intestinal flora and diaper dermatitis in infancy; Gokalp AS et al.; In this study, 40 patients with diaper dermatitis and 20 healthy infants were investigated . Mycological and bacteriological cultures were obtained from affected and healthy skin areas and stool specimens . Candida albicans was isolated simultaneously in 37 out of 40 patients subjected to mycological examination of skin lesions and stool specimen cultures . Of 34 Gram-stained smears from the skin lesions, 27 revealed Candida in hyphal form . In the control group, C . albicans was not grown from the diaper area . No significant difference was observed in the growth of bacteria from the skin with or without lesions (p greater than 0.05) . In conclusion, C . albicans-infection originating from the gastrointestinal tract, plays a major role in diaper dermatitis . Thus, a Gram-stained smear can be used as a practical method in early diagnosis.

Vestn Otorinolaringol, 1990 Jul-Aug, (4), 70 - 4
{Otomycoses in the Kuznetsk region and organization of medical services for this group of population}; Pavlenko SA; In the Kuzbass region the author examined 238 patients, aged 15 to 80 years, with persistent otitis or inflammatory pathologies of the ears that could not be cured by routine therapy . As a result, in 90 patients (37.8%) otomycosis was diagnosed . Mycosis of the external acoustic meatus was identified in 43 patients (55 mycotic ears or 52.4%), fungal otitis media was found in 21 patients (22 ears or 20.9%), and mycosis of the postoperative cavity was detected in 26 patients (28 mycotic cavities or 26.7%) . The following fungi occurred most frequently: Aspergillus niger (75.2%), Candida albicans (6.7%), and Penicillium flavum March (3.8%) . In the presence of fungi the bacterial growth was less significant, thus indicating the predominant role of fungi during otomycosis . Nitrofungin and clotrimazol in combination with 1% decamine ointment were effectively used in the treatment . A good antipruritic drug was 7% chloracetophose ointment . Out of 90 patients complete regression was recorded in 84 cases, with 6 patients having relapses.

Mycopathologia, 1990 Jul, 111(1), 61 - 8
Initial attachment of Candida albicans cells to buccal epithelial cells . Demonstration of ultrastructure with the rapid-freezing technique; Tokunaga M et al.; The rapid-freezing technique was applied in association with scanning and transmission electron microscopy to observe the initial attachment (or contact) of Candida albicans cells to exfoliated human buccal epithelial cells . Low temperature scanning electron microscopy provided detailed three-dimensional morphological features of the yeast-epithelial cell association; adhesion of C . albicans cells to host cells was primarily owing to an interaction between fibrillar layer of the yeast cell wall and the membrane interdigitations of the epithelial cells . Such a particular interconnection between the two cells was confirmed by the freeze-substitution fixation for transmission electron microscopy . These results clearly demonstrate the outermost fibrillar cell wall layer of C . albicans responsible for adhesion to host cells.

J Gen Microbiol, 1990 Jul, 136 ( Pt 7), 1387 - 91
Nutritional stress proteins in Candida albicans; Dabrowa N et al.; Starving cells of Candida albicans synthesize at least seven proteins that represent nutritional-stress proteins (NSP) . Such NSPs are formed by both germination-competent and germination-deficient strains of C . albicans . Heat-shock proteins (HSP) are not formed by starving cells . Germination-competent cells synthesize specific sets of proteins when incubated in a starvation medium that contains the germ-tube-inducing substances N-acetyl-D-glucosamine or L-proline . Both sets of induced proteins were also synthesized by a germination-deficient strain of C . albicans.

Kansenshogaku Zasshi, 1990 Jul, 64(7), 854 - 60
{Effects of immunoglobulin preparations on the opsonic activities against various pathogens}; Ono Y et al.; We evaluated the opsonic activities of human intravenous immunoglobulin (IVIG) preparations against pathogenic organisms by measuring the luminol-enhanced chemiluminescence (CL) from human polymorphonuclear leukocytes (PMN) during the phagocytosis of these organisms . Polyethylenglycol-treated IVIG significantly increased the CL of PMN by opsonization against various bacteria and Candida albicans (p less than 0.01) . The high CL induced by IVIG with intact Fc-fragment showed no significant differences among lots or preparations made by different treatments . In both PMN-CL in the absence of human serum and whole blood CL at low concentration of serum complement, the CL response was not affected by pepsin-treated IVIG . In the severely burned patients' blood with a very low concentration of serum immunoglobulin, IVIG with intact Fc-fragment significantly increased CL (p less than 0.01) . It is suggested that administration of IVIG is useful against infections in these patients . The measurement of whole blood CL in vitro may be useful for evaluating the opsonic activity of IVIG against target pathogens in vivo.

Br J Dermatol, 1990 Jul, 123(1), 9 - 20
Ciprofloxacin-induced photosensitivity: in vitro and in vivo studies; Ferguson J et al.; Ciprofloxacin is one of the new series of broad-spectrum antibiotic quinolones, chemically related to nalidixic acid and which may, therefore, induce photosensitization of human skin . Three in vitro tests for phototoxicity: the destruction of histidine, killing of mouse peritoneal macrophages and inhibition of PHA-stimulated DNA synthesis in human lymphocytes have demonstrated this photosensitizing potential with UVA irradiation at an order of magnitude lower than that for nalidixic acid . The Candida albicans test and photohaemolysis were negative . Controlled irradiation monochromator phototesting of 12 subjects, before, during and after taking ciprofloxacin showed subclinical photosensitivity with significantly lowered minimal 24 h erythema doses at 335 +/- 30 nm, 365 +/- 30 nm and 400 +/- 30 nm but not at 305 +/- 5 nm or above 400 +/- 30 nm.

Infect Immun, 1990 Jul, 58(7), 2228 - 36
Oral and esophageal Candida albicans infection in hyposalivatory rats; Meitner SW et al.; The opportunistic fungus Candida albicans is a major cause of oral and esophageal infections in immuno-compromised patients, individuals on drug therapy, and the chronically ill . Because it has been observed that persons suffering from hyposalivation have an increased prevalence of oral candididiasis, we developed an animal model of infection based on hyposalivation . The objectives of our studies were to understand the mechanisms by which C . albicans causes oral disease and to begin to elucidate the role played by saliva in controlling C . albicans in the oral cavity . Our results showed that (i) oral Candida infection was established by a small challenge inoculum, (ii) mucosal lesions developed in the oral cavities and esophagi of infected rats, and (iii) transmission of oral Candida infection from an inoculated rat to uninoculated cagemates occurred rapidly . In addition, we compared the abilities of a clinical isolate and a spontaneously derived morphological mutant from that isolate to infect hyposalivatory rats and to induce disease . Infection was induced by the morphological mutant in hyposalivatory rats; however, the morphological mutant took significantly longer to transmit oral infection to uninoculated cagemates than did the parental strain.

Infect Immun, 1990 Jul, 58(7), 2139 - 43
Activation of the plasma kallikrein-kinin system by Candida albicans proteinase; Kaminishi H et al.; An extracellular carboxyl proteinase produced by the yeast Candida albicans enhanced vascular permeability when injected into the dorsal skin of guinea pigs . The character and mechanism of the permeability-enhancing reaction were studied in vivo and in vitro . Permeability was not enhanced when the C . albicans proteinase was heat treated (100 degrees C, 5 min) or when it was treated with pepstatin, a specific carboxyl proteinase inhibitor . The permeability reaction induced by the C . albicans proteinase was not affected by pretreatment with antihistamine but was greatly augmented by simultaneous injection of a kinin potentiator, carboxypeptidase N inhibitor . However, the simultaneous injection of a kinin-degrading enzyme, carboxypeptidase B, interfered with the reaction . Furthermore, in vitro conversion of plasma prekallikrein to kallikrein by the C . albicans proteinase was observed, and the reaction was inhibited by corn trypsin inhibitor, an inhibitor of activated Hageman factor, and soybean trypsin inhibitor, a well-known inhibitor of plasma kallikrein . These results indicate that C . albicans proteinase enhances vascular permeability through activation of the plasma kallikrein-kinin system, which generates bradykinin.

Infect Immun, 1990 Jul, 58(7), 2061 - 6
Mannan composition of the hyphal form of two relatively avirulent mutants of Candida albicans; Saxena A et al.; We have previously reported the characteristics of mannans isolated from the yeast forms of two relatively avirulent Candida albicans strains, designated 4918-2 and 4918-10 . Investigations have been expanded to include an analysis of mannans from the hyphal form of these strains as well as from the hyphal form of the parental strain, 4918 . After extraction, mannans were further purified by high-pressure liquid chromatography on a Bio-gel TSK DEAE-5-PW column . Subsequent to either mild acid hydrolysis, alkali hydrolysis, or acetylation followed by acetolysis, the resulting products were fractionated by high-pressure liquid chromatography on an Aminex HPX-42A column . The results of acid hydrolysis showed only minor quantitative differences in the products released from each strain, with mannose constituting the vast majority of product liberated . The profiles of mannooligosaccharides obtained from either alkali hydrolysis or acetolysis for strain 4918-2 showed distinct quantitative differences compared with profiles of the other two strains . Finally, a general characteristic noted is a decrease in the average chain length of mannooligosaccharides in hyphal mannans compared with the yeast counterpart.

Clin Immunol Immunopathol, 1990 Jul, 56(1), 66 - 80
Altered monocyte function in uremia; Gibbons RA et al.; Uremia appears to suppress immune function predisposing patients to infections . When the defect in cellular immunity was studied by exposing mononuclear cells (MNC) from uremic patients and controls to tetanus toxoid, diptheria toxoid, or Candida albicans antigen in vitro, the uremic cells were far less responsive . Monocytes and T cells, which are both involved in the proliferative response to soluble antigens, were isolated from MNC of uremic patients and HLA class II matched controls and incubated with tetanus toxoid . Tetanus toxoid-pulsed uremic monocytes were unable to stimulate the proliferation of HLA identical control T lymphocytes . Lymphocytes from uremic patients, however, were stimulated by tetanus toxoid-pulsed control monocytes . Therefore, the ability of monocytes to function as accessory cells is severely affected by uremia . The uremic monocytes were FcR+, produced IL-1 beta, and expressed levels of HLA class II antigens comparable to controls . Although the biochemical defect in uremic monocytes remains unknown, the abnormality could explain many of the immunological changes of uremia.

J Infect Dis, 1990 Jul, 162(1), 262 - 5
Patterns of guanine nucleotide exchange reflecting disparate neutrophil activation pathways by opsonized and unopsonized Candida albicans hyphae; Diamond RD et al.; Through guanosine triphosphate (GTP) regulatory proteins are crucial components in signal transduction by most soluble and opsonized particulate stimuli, previous data suggest that neutrophil (PMNL) activation by unopsonized hyphae differs . Most of the PMNL superoxide response evoked by unopsonized hyphae was independent of both Ca++ ions and pertussis toxin-sensitive guanine nucleotide regulatory proteins . To determine whether related regulatory proteins were involved in PMNL activation by unopsonized hyphae, separated PMNL plasma membranes were incubated with GTP and a poorly hydrolyzed, radiolabeled GTP analogue, 5'-guanylylimido-diphosphate, then stimulated . Particulate Candida albicans hyphae and soluble chemotactic peptide induced comparable guanine nucleotide release . In contrast, while unopsonized hyphae caused release, it was considerably delayed, though opsonization discernibly affected neither PMNL attachment nor spreading over hyphal surfaces . This paralleled earlier observations of other delayed responses by intact PMNL to unopsonized hyphae: phospholipase C activation, the rise in cytosolic free Ca++ ions, and actin polymerization.

J Bacteriol, 1990 Jul, 172(7), 3898 - 904
Isolation of the Candida albicans histidinol dehydrogenase (HIS4) gene and characterization of a histidine auxotroph; Altboum Z et al.; Genetic studies were done with Candida albicans CBS 562 . Various auxotrophs were isolated following mutagenesis with N-methyl-N'-nitro-N-nitrosoguanidine . SAG5 (his4C), a stable histidine auxotroph defective in histidinol dehydrogenase activity, was characterized and chosen for further molecular studies . Therefore, the C . albicans HIS4 gene was isolated . The gene was obtained from a genomic library of the wild-type strain, which was constructed in plasmid YEp24 . The HIS4 gene was isolated by transformation of a Saccharomyces cerevisiae strain that carried a his4 mutation . The isolated C . albicans HIS4 gene complemented S . cerevisiae his4A, his4B, his4C, and his4ABC mutant strains, which indicates that the clone contains the entire HIS4 gene . The gene was isolated on plasmid pSTC7, whose physical map was constructed with BamHI, SalI, and EcoRV restriction endonucleases, locating the HIS4 gene on a 14-kilobase-pair DNA fragment . Hybridization experiments with HIS4 and C . albicans genomic DNA showed correspondence between the restriction patterns of the gene with that of the chromosomal DNA, indicating that the gene originates from C . albicans and appears in a single copy . Chromosomes of C . albicans CBS562 and four other strains were resolved by orthogonal-field alteration gel electrophoresis . The electrokaryotyping results showed heterogeneity in chromosomal sizes . The electrokaryotyping of CBS 562 showed a resolution of six chromosomal bands, three of which seemed to be doublets . The C . albicans HIS4 gene was located on the largest resolvable chromosome in all of the strains.

Rev Esp Enferm Dig, 1990 Jul, 78(1), 31 - 4
{Delayed gastric emptying following subtotal gastrectomy}; Giner M et al.; A case of prolonged gastric retention, after truncal vagotomy and antrectomy, is reported . The clinical picture was initially thought to be due to an organic obstruction . The patient was reoperated, having a Billroth-II anastomosis converted into a Roux--en--Y . The gastric retention reappeared soon after the reoperation . After a long period on nutritional support, the patient resumed tolerance first to a solid food and then to liquids . Later a bezoar of Candida albicans was discovered in the gastric stump . After gastric lavage, the patient remained free of symptoms . The importance on the assessment by gastroscopy as well as the conservative treatment in case of postoperative gastric retention is emphasized in this paper.

Mycoses, 1990 Jul-Aug, 33(7-8), 393 - 404
The effects of amorolfine and oxiconazole on the ultrastructure of Trichophyton mentagrophytes . A comparison; Melchinger W et al.; Amorolfin applied in concentrations of 0.1-100 micrograms ml-1 caused considerable damages to the ultrastructure of Trichophyton mentagrophytes: Electron-transparent areas appear in the cytoplasma . The cell wall increases in thickness . 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 final, vigorous ultrastructural damage . The feature of the damage caused by amorolfin is comparable to that effected by azole antifungals . The characteristics of the ultrastructural changes are similar to those due to amorolfin in the yeast species Candida albicans.

Mycoses, 1990 Jul-Aug, 33(7-8), 383 - 92
Antifungal action of latex saps from Lactuca sativa L . and Asclepias curassavica L; Moulin-Traffort J et al.; Asclepias curassavica and Lactuca sativa latex saps inhibit the growth of Candida albicans because they degrade a great number of yeasts . This was confirmed by scanning and transmission electron microscopy observations . After a contact of 4 h and 6 h yeasts are deformed and emptied of their cytoplasmic content . Moreover, it appears that these saps, particularly Asclepias, also act on the cell wall: the substances presumed to be responsible for these effects were probably terpens and cardenolids but also enzymes, in particular glucanases.

Mycoses, 1990 Jul-Aug, 33(7-8), 353 - 8
Antifungal combination therapy in localized candidosis; Polak A; A mouse model of localized candidosis in air-filled subcutaneous cysts imitating thrush has been developed . We have now tested various antifungal combinations in this animal model . Flucytosine (5-FC) + amphotericin B (Amph B) showed the highest efficacy, a clear additive or even synergistic effect was seen . The combination of 5-FC + imidazole or triazole derivative was less efficacious, an additive effect was rare . The combination of 5-FC + Amph B was also tested against Candida albicans strains showing various degrees of 5-FC-resistance . A significant reduction in 5-FC-resistant mutants was seen after the treatment with the combination.

Mycoses, 1990 Jul-Aug, 33(7-8), 335 - 52
Saperconazole: a selective inhibitor of the cytochrome P-450-dependent ergosterol synthesis in Candida albicans, Aspergillus fumigatus and Trichophyton mentagrophytes; Vanden Bossche H et al.; The N-1-substituted triazole antifungal, saperconazole, is a potent inhibitor of ergosterol synthesis in Candida albicans, Aspergillus fumigatus and Trichophyton mentagrophytes . Fifty % inhibition is already achieved at nanomolar concentrations . The saperconazole-induced inhibition of ergosterol synthesis coincides with an accumulation of 14-methylated sterols, such as 24-methylenedihydrolanosterol, lanosterol, obtusifoliol, 14 alpha-methylfecosterol, 14 alpha-methylergosta-8,24(28)-dien-3 beta-6 alpha-diol and 14 alpha-methylergosta-5,7,22,24(28)-tetraenol . This indicates that saperconazole interferes with the cytochrome P-450 (P-450)-dependent 14 alpha-demethylation of lanosterol and/or 24-methylenedihydrolanosterol . Saperconazole forms stable drug-P-450-complexes by binding via its free triazole nitrogen to the heme iron and via its N-1 substituent to the apoprotein moiety . The triazole derivative is a highly selective inhibitor of the 14 alpha-demethylase in fungal cells . It is a poor inhibitor of the 14 alpha-demethylation of lanosterol in rat and human liver cells . Saperconazole is, at concentrations as high as 10 microM, devoid of effects on the P-450-dependent cholesterol side-chain cleavage and 11 beta-hydroxylase, 17,20-lyase,21-hydroxylase and aromatase . Saperconazole does not interfere with the 2 alpha, 6 alpha-, 6 beta- and 7 alpha-hydroxylations of testosterone in microsomes from male rat liver . At high concentrations (greater than 5 microM) an inhibition of the 16 beta-hydroxylations is seen.

J Dent Assoc Thai, 1990 Jul-Aug, 40(4), 177 - 84
{Glass bead sterilization of orthodontic pliers}; Nisalak P et al.; The study on sterilization of orthodontic pliers by using glass bead sterilizer at 450 F was performed . Microorganisms used in this experiment were Staphylococcus aureus ATCC 25933, Bacillus subtilis ATCC 6633, Candida albicans ATCC 10231 and mixed microorganisms in human saliva . The result showed that after the pliers were scrubbed with alcohol and sterilized for 3 minutes with glass bead sterilizer, all vegetative cells and bacterial spores were killed in every test . This study indicated that glass bead sterilizer is capable of sterilizing orthodontic pliers and can be a useful adjunct when rapid chairside sterilization is desired.

J Gen Microbiol, 1990 Jul, 136 ( Pt 7), 1421 - 8
Differences in the antigenic expression of immunomodulatory mannoprotein constituents on yeast and mycelial forms of Candida albicans; Torosantucci A et al.; The expression of a strongly immunomodulatory mannoprotein complex (GMP) in the different forms of growth of the human commensal and opportunistic pathogen Candida albicans was studied using a monoclonal antibody (mAb AF1) directed against an oligosaccharide epitope of GMP . Immunofluorescence revealed that the surface of the yeast cells was highly reactive with mAb AF1, but that the reactivity was greatly reduced or disappeared during mycelial conversion . This modulation was shared by a number of strains of C . albicans, and was not solely a temperature- or nutrition-dependent phenomenon . Hypha-deficient strains (A12 and CA2) did not show variations of surface fluorescence under environmental conditions which were permissive for hyphal conversion (incubation in N-acetylglucosamine or Lee's medium, at 37 degrees C) . GMP extracts from yeast and mycelial forms of the fungus were separated into three chromatographically distinct, high molecular mass mannoprotein fractions (F1, F2 and F3), which were tested individually by indirect ELISA for mAb AF1 recognition . All yeast-derived constituents and two (F2 and F3) of the hyphal mannoproteins were recognized by the mAb . The low or absent reactivity of the F1 constituent from hyphal cells was confirmed by immunoblots . Irrespective of their source (yeast or mycelial), all fractions reacted to a similar extent with a polyclonal anti-Candida serum . Overall, the data suggest changes in epitope specificity and/or confinement of reactive constituents in the inner wall layers as possible mechanisms of modulated expression of mAb AF1-reactive epitope during mycelial conversion.

J Immunol, 1990 Jun 15, 144(12), 4651 - 6
Evidence for compartmentalization of functional subsets of CD2+ T lymphocytes in atopic patients; Wierenga EA et al.; Lymphokine secretion profiles were studied of human allergen-specific CD4+ T lymphocyte clones (TLC) . To this aim, panels of house dust mite Dermatophagoides pteronyssinus (Dp)-specific TLC were generated from two atopic Dp-allergic patients, suffering from severe atopic dermatitis (AD1) and allergic asthma (AD2), respectively, and from a non-atopic individual (NAD) . From AD1 additional TLC were cloned specific for tetanus toxoid or Candida albicans, both Ag that were not relevant for the atopic state of this patient . Secretion of IL-2, IL-4, and IFN-gamma was determined after specific stimulation of these TLC, using autologous monocytes as APC . With respect to the production of IL-4 and IFN-gamma, clearly distinct profiles were observed . All Dp-specific TLC from both atopic donors produced IL-4 but not IFN-gamma, whereas the Dp-specific TLC from NAD, as well as the tetanus toxoid- and C . albicans-specific TLC from AD1, all produced IFN-gamma but not or small quantities of IL-4 . Most TLC from all panels produced IL-2 . These lymphokine profiles were consistent for at least 3 days and were neither dependent on the dose of allergen nor on the atopic or nonatopic state of the donor of APC . The functional consequence of these restricted lymphokine profiles was stressed by the observation that, whereas Dp-specific TLC from AD1 and AD2 supported in vitro IgE production, this support could be abrogated by a Dp-specific TLC from NAD . The present results suggest that CD4+ T lymphocytes that produce IL-4, but not IFN-gamma, occur in high frequencies in the allergen-specific T cell repertoires of atopic donors, which may have important implications for the pathomechanism of atopic disease.

Kokyu To Junkan, 1990 Jun, 38(6), 605 - 8
{A case of candida endocarditis with consecutive measurement of serum mannan and D-arabinitol concentrations}; Maeno K et al.; We encountered a case of an 83-year-old patient with candida endocarditis . He had been diagnosed as having aortic regurgitation with moderately calcified aortic valve 5 years previously, and had received medication . He was admitted to our hospital because of pancreatic cancer . He had high fever from the time of his admission and antibiotics produced no effect . Candida albicans was detected in arterial blood culture . We also detected antibody against Candida albicans, and investigated serum mannan and the D-arabinitol creatinine ratio several times . We performed echo-cardiographic examination and recorded a vegetation at the aortic valve . Rising antibody titers against Candida albicans, mannan antigenemia and an elevated creatinine ratio were also observed . So we concluded that these examinations were also effective in the diagnosis of candida infection . Finally, this patient died of cerebral hemorrhage and was autopsied . Macroscopic findings showed mass-like vegetation involving the aortic valve, and microscopic findings showed candida organisms scattered within the vegetation.

Minerva Med, 1990 Jun, 81(6), 481 - 3
{Therapy of systemic candidiasis}; Cascioli CF et al.; Candida septicaemia is an increasingly common problem . Candida Albicans may be found in yeast form in the intestinal tract, vagina, skin and mucous membranes of apparently healthy individuals . The organism is ubiquitous, and systemic disease occurs almost exclusively in individuals whose resistance to infections is impaired . Diagnosis of invasive candidiasis is often delayed because of the high rate of false negative results on blood cultures, the lengthy period of time required for the identification of positive cultures and the aspecificity of positive findings on blood cultures . The most effective treatment is a combination of amphotericin B and 5-flucytosine . Treatment must be prolonged for 7 days after the first negative culture . Amphotericin B must be administered in doses of 0.5-1 mg/kg/day . Meningitis requires the intrathecal injection of amphotericin B in doses of 0.1 mg/kg/day . Amphotericin B does not induce resistance, and it is highly nephrotoxic, so that blood urea, electrolytes, serum creatinine and platelets must be monitored . 5-flucytosine is not very toxic it does induce resistance after prolonged use . The dose is 100-200 mg/kg/day given orally at 6-hour intervals.

Infect Immun, 1990 Jun, 58(6), 1796 - 801
Effect of Friend leukemia virus infection on susceptibility to Candida albicans; Moors MA et al.; Previous studies have demonstrated that Friend leukemia virus (FLV) induces a profound immunosuppression in susceptible mice . The studies described in this report indicate that mice infected with FLV have an increased susceptibility to subsequent infection with the opportunistic pathogen Candida albicans, as measured by increased numbers of C . albicans CFU in the kidneys of FLV-infected mice relative to uninfected controls . Experiments in which the NB-tropic and N-tropic strains of FLV were used suggest that virus replication or the resulting virus burden may be important in the observed increased susceptibility to C . albicans . Since neutrophils are believed to be important in the response of mice to systemic Candida infections, the effect of FLV infection on neutrophil candidacidal activity was investigated . The percentage of neutrophils present in unfractionated Proteose Peptone-elicited peritoneal exudates of mice infected with FLV for 14 days was significantly lower than in uninfected control mice or mice infected with FLV for 6 or 10 days . When neutrophils from FLV-infected and control mice were purified, adjusted to equal concentrations, and tested for in vitro candidacidal activity, neutrophils from mice infected with FLV for 14 days were deficient in their ability to kill C . albicans relative to normal controls and mice infected with FLV for 6 or 10 days . Addition of normal mouse serum increased killing in all groups but did not restore candidacidal activity of neutrophils from mice infected with FLV for 14 days to levels of control neutrophils or neutrophils from mice infected for 6 or 10 days with the virus . These results suggest a defect in neutrophil function, at the later stages of FLV infection, involving in vitro candidacidal activity . In addition, neutrophils from FLV-infected mice may be deficient in in vivo chemotactic activity . These defects in neutrophil function could account, at least in part, for the observed increased susceptibility of FLV-infected mice to C . albicans.

Mycoses, 1990 Jun, 33(6), 265 - 82
Pathogenicity determinants of Candida; Ghannoum MA et al.; The incidence of infections due to Candida albicans and other related species has increased in recent years . A number of factors have contributed to this, e.g . the use of a wide range of potent antibacterial and immunosuppressive therapeutic agents and the increased incidence of immune-deficiency diseases such as AIDS . Pathogenicity determinants which confer virulence on C . albicans, and other Candida species to a lesser extent, have been reviewed . These include factors related to species and strains, adherence, dimorphism, toxin and enzyme production and cell surface composition . This review clearly shows that C . albicans virulence is a function of a multiplicity of factors working jointly to overcome the host defences . A lack or debility in any of these parameters will reflect negatively on its infectivity and make it difficult for Candida to establish itself, particularly in a healthy individual.

Immunol Cell Biol, 1990 Jun, 68 ( Pt 3), 179 - 85
Murine candidiasis: susceptibility is associated with the induction of T cell-mediated, strain-specific autoreactivity; Ashman RB; Inbred mice can be classified as susceptible or resistant to systemic infection with the yeast Candida albicans by histopathological evaluation of tissue lesions . Candida-specific memory T cell responses generated by resistant BALB/c mice are vigorous and sustained, whereas those displayed by susceptible CBA/H mice are weak . When spleen cells from immune mice were activated by culture with candida antigens in vitro, and injected into syngeneic and allogeneic recipients in the absence of further antigenic stimulation, cells from CBA/H mice induced a specific inflammatory response only in CBA/H recipients . In contrast, cells from immune BALB/c mice showed no specific activity . The effector cells were identified as T cells of the cytotoxic/suppressor subclass (CD4-, CD8+); and analysis in various F1 hybrid mice showed that reactivity was expressed only in animals carrying CBA/H genes . The data thus indicate that susceptibility to C . albicans infection is associated with the induction of a T cell subpopulation that has the potential to react specifically against unmodified self antigens expressed by the susceptible strain.

Immunol Cell Biol, 1990 Jun, 68 ( Pt 3), 173 - 8
An immunodominant antigen of Candida albicans shows homology to the enzyme enolase; Franklyn KM et al.; Antibody to an immunodominant antigen of approximately 48 kDa is found in a high proportion of patients with mucocutaneous or systemic infections of the yeast Candida albicans . A cDNA encoding part of the 48 kDa antigen has been isolated . From the deduced amino acid sequence of the cDNA clone, the 48 kDa antigen shows homology to the enzyme enolase.

FEMS Microbiol Lett, 1990 Jun 1, 57(3), 211 - 4
Antifungal drugs affect adherence of Candida albicans to acrylic surfaces by changing the zeta-potential of fungal cells; Miyake Y et al.; The effect of sub-inhibitory concentrations of antifungal drugs on the adherence of Candida albicans to acrylic surfaces was investigated . Among five antifungals tested, azalomycin F and aculeacin A significantly enhanced the adherence . The zeta-potential of fungal cells was affected by antifungal drugs, whereas no significant change in cell surface hydrophobicity was observed . The relationship obtained between the change in the adherence and that in zeta-potential suggests that the enhanced adherence was caused by decreased electric repulsive forces.

Br J Clin Pract, 1990 Jun, 44(6), 219 - 22
An open multicentre study of the efficacy and safety of a single dose of fluconazole 150 mg in the treatment of vaginal candidiasis in general practice; Phillips RJ et al.; The efficacy and tolerability of fluconazole given as a single oral dose of 150 mg were assessed in 1,017 patients in general practice presenting with signs and symptoms of vaginal candidiasis . At the review visit 7-14 days after treatment, about 95 per cent of patients reported being either cured or improved . High vaginal swabs taken from 43 patients out of 50 who failed following treatment revealed Candida albicans in 17 (1.8 per cent) . Efficacy in patients with predisposing factors (oral contraceptives, antibiotics and recurrent vaginal candidiasis - four episodes or more in previous year) was not significantly different from that in those without these factors . Of patients who had received previous intravaginal therapy for vaginal candidiasis, 88 per cent preferred fluconazole, 10 per cent previous therapy and two per cent had no preference . Investigators assessed efficacy after fluconazole as excellent or good in 91 per cent and tolerability as excellent or good in 91 per cent of patients . Significant adverse effects were reported in less than one per cent of patients.

Curr Genet, 1990 Jun, 17(6), 487 - 91
Efficient translation of the UAG termination codon in Candida species; Santos M et al.; Clinical isolates of the dimorphic fungus Candida albicans encode a tRNA that, in a cell-free translation system prepared from the yeast Saccharomyces cerevisiae, efficiently translates the amber (UAG) termination codon . Unusually, the efficiency of this UAG read-through in the heterologous cell-free system is not further enhanced by polyamines . The suppressor tRNA is also able to efficiently translate the UAG codon in the rabbit reticulocyte cell-free system and with efficiencies approaching 100% in a homologous (C . albicans) cell-free system . That the suppressor tRNA is nuclear-encoded is demonstrated by the lack of activity in purified C . albicans mitochondrial tRNAs . Finally, UAG suppressor tRNA activity is also demonstrated in three other pathogenic Candida species, C . parapsilosis, C . guillermondii and C . tropicalis . These results suggest that some, but not all, Candida species have evolved an unusual nuclear genetic code in which UAG is used as a sense codon.

J Gen Microbiol, 1990 Jun, 136 ( Pt 6), 1067 - 75
The role of microfilaments and microtubules in apical growth and dimorphism of Candida albicans; Yokoyama K et al.; Cytoskeleton inhibitors were used to study morphogenesis in the pathogenic and dimorphic fungus Candida albicans . Nocodazole is a specific microtubule inhibitor and chloropropham (CIPC), at high concentrations, is an inhibitor of microtubules and microfilaments . Distribution of microtubules and microfilaments was studied by immunofluorescence techniques using anti-tubulin antibody with FITC-conjugated secondary antibody, and by staining with Rh-phalloidin . Nocodazole did not arrest apical cell elongation at a concentration (20 micrograms ml-1) that inhibited nuclear division and migration . Cytoplasmic and nuclear microtubules disappeared within 30 min in filamentous cells under these conditions . However, the Rh-phalloidin-stained actin granules which were localized in the tips of filamentous cells, and the microfilaments, were arranged normally at this concentration of nocodazole . Growth, and normal distribution of microtubules and microfilaments, were inhibited by a high concentration (200 micrograms ml-1) of CIPC . At a concentration (100 micrograms ml-1) of CIPC that permitted nuclear division, apical cell elongation was arrested, and filamentous growth was converted into yeast growth . At this concentration of CIPC, microtubules were distributed normally in filamentous cells . Long microfilaments were not observed, and actin granules did not localize in the tips of filamentous cells, but were distributed throughout the cytoplasmic cortex . Our results show that cytoplasmic microtubules are not essential for the elongation of filamentous cell tips but that microfilaments are apparently essential for this process.

J Gen Microbiol, 1990 Jun, 136 ( Pt 6), 1059 - 65
Internalization of lucifer yellow in Candida albicans by fluid phase endocytosis; Basrai MA et al.; Lucifer yellow (LY), an impermeable fluorescent dye used as a marker for fluid phase endocytosis, was internalized by Candida albicans . As observed by fluorescence microscopy, incubation of C . albicans with LY in potassium phosphate buffer (pH 6.0) and glucose (2%, w/v) resulted in localization of the dye inside vacuoles . Sodium azide and carbonyl cyanide m-chlorophenylhydrazone, which are inhibitors of energy metabolism, decreased the uptake of the dye . The optimum temperature for uptake was 30 degrees C; no internalization was observed at 0 degrees C . Quantification of cell-associated LY by fluorescence spectrometry showed an uptake linear with time and not saturable over a 400-fold range of concentration . Thus, C . albicans internalized LY into vacuoles by a nonsaturable and time-, temperature- and energy-dependent process consistent with fluid phase endocytosis . Both the yeast and mould phase of this dimorphic fungus endocytosed LY . Growth in complex medium appeared to be required to enable the cells to internalize LY . However, addition of peptone or yeast extract to the phosphate buffer/glucose assay medium interfered with LY uptake by causing an apparent increase of exocytosis . These studies provide the first evidence of fluid phase endocytosis in C . albicans and may explain how some large molecules, such as toxins and cationic proteins, enter C . albicans.

Appl Environ Microbiol, 1990 Jun, 56(6), 1974 - 6
Improved assay for surface hydrophobic avidity of Candida albicans cells; Hazen KC et al.; A simple method that distinguishes among hydrophobic avidity levels of highly hydrophobic isolates of the pathogenic fungus Candida albicans is described . This method involves mixing polystyrene microspheres at different concentrations with a constant concentration of yeast cells and plotting the data in accordance with the Langmuir isotherm equation . A 10-fold difference between the C . albicans isolates with the lowest and highest avidity (KH) values was found . This method may also demonstrate that surface hydrophobic sites with different avidities are present within a yeast cell population.

J Clin Microbiol, 1990 Jun, 28(6), 1236 - 43
Computer-assisted methods for assessing strain relatedness in Candida albicans by fingerprinting with the moderately repetitive sequence Ca3; Schmid J et al.; When used to probe EcoRI-digested Candida albicans DNA, the moderately repetitive sequence Ca3 generated a Southern blot hybridization pattern which included 15 to 25 bands, depending upon the strain . The pattern was stable through 400 generations in each of three independent strains but variable between most of 46 unrelated tester strains, making it a very effective probe for discrimination between strains . Computer-assisted methods (Dendron) were developed for storage of Ca3 patterns in data files, calculation of similarity (SAB) values between strains based upon band positions and intensities, and generation of histograms and dendrograms based on SAB values for all strains or any subset of strains in large epidemiological studies . In testing the effectiveness of the system, it was found that (i) multiple isolates from different body locations of the same healthy individual could represent either the same strain or different strains, (ii) isolates from oral lesions of a husband and wife represented the same strain, (iii) strains isolated from the mouths of 10 healthy individuals on the same day and in the same geographical location were as dissimilar on average as the 46 unrelated tester strains, and (iv) strains isolated from seven immunocompromised patients hospitalized over a 2.5-month period in the same hospital were highly similar, indicating nosocomial origin . The apparent effectiveness of these fingerprinting methods and the Dendron program suggests that interlaboratory procedures for fingerprinting should be standardized and all patterns should be analyzed and stored in a common and accessible data base for broad epidemiological analysis.

J Antibiot (Tokyo), 1990 Jun, 43(6), 715 - 21
Calcium-dependent anticandidal action of pradimicin A; Sawada Y et al.; Pradimicin A shows candicidal activity at 10 micrograms/ml in vitro . The action of pradimicin A on Candida albicans cells involves a set of specific cell surface interactions in a Ca2(+)-dependent manner . These include binding to the mannan components on the cell surface and subsequent interactions at the level of the plasma membrane, causing K+ leakage and cell death . The protoplasts prepared from C . albicans undergo lysis rapidly when treated with pradimicin A . These results suggest that pradimicin A acts primarily on the candidal plasma membrane, leading to a perturbation of membrane function.

South Med J, 1990 Jun, 83(6), 687 - 9
Candida albicans infected pseudocyst in a postpartum woman; Chia N et al.; We have presented the case of a postpartum woman with a pseudocyst infected with C albicans and have reviewed the relevant literature . The patient did well with surgical drainage of the pseudocyst and adjunctive therapy with amphotericin B . Candida species isolated from a pancreatic pseudocyst or abscess should be considered pathogens, and the patient should receive aggressive therapy.

J Am Osteopath Assoc, 1990 Jun, 90(6), 509 - 14
Risk factors of nosocomial bacteremia associated with pulmonary artery catheters in a critical care unit; Glowacki M et al.; An epidemiologic investigation at a community teaching hospital identified 17 cases of endemic primary nosocomial bacteremias associated with the use of pulmonary artery catheters (PACs) . A matched-case control study was undertaken to identify risk factors associated with these bacteremias . Factors significantly associated with bacteremia were length of hospitalization; length of stay in the critical care unit; length of time the PAC introducer was left in place and used as an intravenous (IV) access device after PAC withdrawal; respiratory compromise; PAC site infection; prior infections at other sites; concomitant hyperalimentation; and number of IV piggyback administrations per day prior to onset of bacteremia . Pathogens isolated included coagulase-negative Staphylococcus species (55.6%), Staphylococcus aureus (22.2%), Candida albicans (14.8%), and enterococci (7.4%) . These pathogens were generally resistant to antibiotics given before the development of bacteremia . Bacteremia was associated with significant mortality, a prolonged hospital stay, and increased hospital charges . This study identifies important risk factors to consider in formulating guidelines to prevent and control PAC-associated nosocomial infections.

J Infect Dis, 1990 Jun, 161(6), 1276 - 83
Evidence for a role for secreted aspartate proteinase of Candida albicans in vulvovaginal candidiasis; De Bernardis F et al.; The presence of the secretory aspartate (acid) proteinase in the vaginal fluid of candidal vaginitis patients and controls was studied by ELISA and immunoblot (Western blot) . In addition, a proteinase-deficient mutant strain of Candida albicans (IR24) was compared with the wild-type parent strain (10261) for ability to infect the vagina of pseudoestrus rats under estradiol treatment . Among the 67 women examined, proteinase was detected only in 22 harboring C . albicans (range, 42-233 ng/ml of vaginal fluid), at concentrations significantly higher in the 14 vaginitis patients than in the 8 asymptomatic fungal carriers . Western blots confirmed the presence of only one protein band of approximately 43 kDa, corresponding to that of the purified proteinase, in the ELISA-positive vaginal fluids . Experimental vaginal infection was significantly more extensive and persistent in rats infected with the proteinase-producer strain than in those challenged with the proteinase-deficient mutant, and the enzyme was detected in the vaginas of the former but not of the latter animals . Both strains 10261 and IR24 developed hyphal forms to a roughly similar extent during infection, and both showed a comparable adherence in vitro to vaginal and buccal epithelial cells . The clinical and experimental evidence support a role for secretory proteinase as a virulence factor in the pathogenesis of candidal vaginitis.

Cell Immunol, 1990 Jun, 128(1), 89 - 100
Growth inhibition of Candida albicans by interleukin-2-induced lymph node cells; Beno DW et al.; Previous reports have demonstrated natural killer cells (NK) to exert growth inhibitory effects against certain fungi, but not against Candida albicans . In this investigation, interleukin-2 (IL-2)-induced lymph node cells with phenotypic and functional characteristics of NK were shown to inhibit the growth of C . albicans . Growth inhibition was evaluated by both the release of 51Cr by the fungus and the inhibition of microcolony growth of the fungus on Sabouraud's dextrose agar . Lymphoid cells derived from C57Bl/6 mice and immediately assessed for hyphal growth inhibition showed little or no activity . However, significant hyphal growth inhibition was produced by lymph node cells cultured with recombinant IL-2 . Growth inhibitory activity was dependent upon the concentration of IL-2 and was mediated by nonadherent lymphocytes which lysed an NK-susceptible and to a lesser extent an NK-resistant cell line . Treatment of the IL-2-induced cells with anti-asialo GM1 but not anti-Thy-1 and complement abrogated growth inhibition of C . albicans . These results suggest that IL-2-induced lymph node cells with functional and phenotypic characteristics similar to those of activated NK, mediate in vitro growth inhibition of the hyphal form of C . albicans.

Infect Immun, 1990 Jun, 58(6), 1902 - 8
Characteristics of Candida albicans adherence to mouse tissues; Cutler JE et al.; An ex vivo binding assay originally described for determining lymphocyte homing receptors was adapted for studying Candida albicans-host cell interactions in unfixed tissue sections . BALB/cByJ mice were sacrificed, and various organs were removed, rapidly frozen on dry ice, and sectioned . C . albicans yeast cells were suspended to 1.5 x 10(8) cells per ml in Dulbecco modified Eagle medium supplemented with 5% newborn calf serum, and 100 microliters of the suspension was added to tissue sections for 15 min with rotation at 4 degrees C or at 22 to 24 degrees C . The sections were then fixed in glutaraldehyde, washed, and examined . Stationary-phase yeast cells adhered better than log-phase cells, and adherence characteristics were similar at 4 degrees C and 22 to 24 degrees C . Yeast cells from nine strains of C . albicans showed similar tissue specificity . Adherence to lymph node tissue was confined to subcapsular spaces and trabecular sinuses . In the spleen, yeast cells bound to the marginal zones . In both tissues, an association of yeast cells with tissue macrophages was suggested by results with macrophage-specific monoclonal antibodies and fluorescent or immunoperoxidase staining techniques . C . albicans adhered to convoluted tubules, glomeruli, and the tunica media of arterioles in the kidney . During experimentally induced fungemia in mice, C . albicans yeast cells associated with the same tissue sites as in the ex vivo assay, except that binding to renal arterioles was not seen in the in vivo test . A strain of Saccharomyces cerevisiae showed some adherence patterns in common with C . albicans, which indicates that tissue adherence is not sufficient for virulence . Mechanisms of attachment were not determined, but strains of C . albicans varied quantitatively in their ability to attach, and binding was inhibited by chelators of divalent cations.

Infect Immun, 1990 Jun, 58(6), 1552 - 7
Isolation and characterization of cell surface mutants of Candida albicans; Whelan WL et al.; Mutant strains of Candida albicans were obtained by selecting for cells that escaped agglutination by a polyclonal antiserum raised against standard C . albicans serotype A isolate B311 . Mutants were obtained from strains B311 and B792 and from four strains isolated from patients with acquired immunodeficiency syndrome . All 15 tested mutants retained characteristic sugar assimilation patterns . All but one of the mutants retained the ability to form germ tubes and chlamydospores . Two mutants from an acquired immunodeficiency syndrome-derived isolate were deficient in binding complement ligands iC3b and C3d, whereas another mutant was deficient in binding ligand iC3b but not C3d . The hyphae of these three mutants lacked antigens when examined by Western immunoblotting with monoclonal antibody Ca-A, which detects several glycoproteins, including C3d-binding proteins . One of the complement-binding-deficient mutants was tested for its ability to colonize the gastrointestinal tract of rabbits but did not differ from the wild-type parent in site or degree of colonization . The proton magnetic resonance spectra of bulk mannan carbohydrate extracted from tested mutants showed the loss of a signal characteristic of the mannosyl alpha-PO4 linkage; each mutant also had a distinct pattern of other changes.

Infect Immun, 1990 Jun, 58(6), 1527 - 31
Effect of proteolytic activity on virulence of Candida albicans in burned mice; Neely AN et al.; Total circulating proteolytic activity (PA) was determined by measuring the acid-soluble 125I-protein fragments generated per 100 microliters of serum incubated with 125I-protein at 37 degrees C for 15 min . Normal mice had low circulating PA (1.3 +/- 0.2 micrograms/100 microliters), and burned mice had a higher average PA; the actual value depended on the time of measurement postburn . We measured the effect on mortality and on circulating PA of challenging normal and burned mice with high-virulence strain Candida albicans MY 1044 and its less virulent mutant MY 1049 . Burned and normal mice challenged with a high dose (10(5)) of MY 1044 had high mortality (greater than 90%) and high circulating PA (greater than 33 micrograms generated per 100 microliters) . Burned mice challenged with a lower dose (10(4} of MY 1044 had moderate mortality (63%) and lower PA (27.2 +/- 4.2 micrograms/100 microliters) . All other groups of mice, including burned mice challenged with 10(5) MY 1049, had low mortality (less than 10%), and PAs were less than 22 micrograms/100 microliters . Augmentation of burned mice challenged with 10(5) MY 1049 with proteinase significantly increased mortality; with treatment of burned mice challenged with 10(5) MY 1044 with proteinase inhibitor significantly decreased mortality . We conclude that mortality correlated with total circulating PA; that the contribution to this net PA was the background PA level in the normal mice, the PA associated with the burn, and the PA caused by infection with a C . albicans strain with a particular virulence; that most deaths caused by C . albicans occurred past a PA threshold of 25 micrograms/100 microliters in the host; and that the number of burned and infected mice that died of candidiasis could be modulated by the addition of proteinases or proteinase inhibitors to the host . This last finding may lead to some novel treatments for candidiasis in burned hosts.

Infect Immun, 1990 Jun, 58(6), 1514 - 7
A model of sustained gastrointestinal colonization by Candida albicans in healthy adult mice; Samonis G et al.; Three-month-old male Crl:CD1(ICR)BR and C3H/HeJ mice were fed chow containing Candida albicans for 14 days, while similar control mice were fed regular food . Stool cultures were done for all mice before and after administration of the special diet . Stool cultures were repeated 48 h, 1 week, and 1 and 3 months after stopping the diet for Crl:CD1(ICR)BR mice and again 5 months afterward for C3H/HeJ mice . Some animals were sacrificed at the end of the special diet, and cultures and histopathologic examination of various organs were performed . Colonization with C . albicans occurred in the Candida-fed mice, and the fungus was maintained in the gastrointestinal tract at a concentration of 10(3) to 10(4) CFU/g of stool for up to 5 months . There was no histologic evidence of organ infection with Candida spp . The fungus was not found in stool cultures or organs of mice in the control group . The results suggest that persistent gastrointestinal colonization of adult mice by C . albicans can be achieved without immunosuppression . Thus, with additional manipulations, this model could be useful for studying the role of gastrointestinal colonization by C . albicans in the development of systemic infection.

Carbohydr Res, 1990 Jun 1, 199(2), 215 - 26
Structure of the D-mannan of Candida stellatoidea IFO 1397 strain . Comparison with that of the phospho-D-mannan of Candida albicans NIH B-792 strain; Tojo M et al.; The structure of the D-mannan of Candida stellatoidea IFO 1397 strain, which has properties identical to those of the phospho-D-mannan of C . albicans serotype B strain, does not contain phosphate groups, and its 1H- and 13C-n.m.r . spectra are quite similar to those of the phospho-D-mannan of C . albicans NIH B-792 strain . However, the 1H-n.m.r . and 1H-13C-correlation n.m.r . spectra of the products obtained by digestion with alpha-D-mannosidase of C . stellatoidea D-mannan considerably differed from those of the corresponding digestion products of the C . albicans phospho-D-mannan . Additionally, the enzyme-linked immunosorbent assay, by means of a monoclonal antibody corresponding to (1----2)-linked beta-D-oligomannosyl residues, of the phospho-D-mannan of the same C . albicans strain indicated that the C . stellatoidea D-mannan does not contain any (1----2)-linked beta-D-oligomannosyl residues . The absence of these residues may be used as one of the criteria of chemotaxonomical identification of C . stellatoidea spp.

Int J Dermatol, 1990 Jun, 29(5), 337 - 9
Onychomycosis and AIDS . Clinical and laboratory findings in 62 patients; Dompmartin D et al.; The results of a study on onychomycosis in AIDS related complex and AIDS patients presenting for dermatology consultation at an infectious diseases department are reported . The clinical results showed that most patients presented a proximal white superficial onychomycosis . The association with a clinical interdigital involvement was rare, but the association with a mycotic plantar keratoderma was more frequent . The laboratory results showed that dermatophytes were the most frequent etiologic agents, especially Trichophyton rubrum (58%) . Although most of these patients presented an oral candidiasis, Candida albicans was isolated only in seven patients' nails . Surprisingly, Pityrosporum ovale was the only etiologic organism that was found in two patients . This result was confirmed with a histologic examination.

Br J Gen Pract, 1990 Jun, 40(335), 238 - 40
The inflammatory cervical smear: a study in general practice; Kelly BA et al.; This study set out to determine whether the term 'inflammatory' in a cervical smear report implies underlying infection or whether it could be masking cancerous or precancerous changes . Of 826 smears taken in one practice over one year, 42 demonstrated some degree of inflammatory change . Thirty four of these women presented for swabs and almost half (47%) had a microbiologically proven infection . This group was further subdivided, and of those whose smears were reported as simple 'inflammation', just over one third (35%) were infected but of those whose smears were reported as 'severe inflammation', over two thirds were infected (73%) . The commonest organisms isolated were Gardnerella vaginalis and Candida albicans . It would therefore appear to be worthwhile to treat patients who report severe inflammation with metronidazole and with anti-fungal pessaries before the smear is repeated . Following treatment two women went on to show dyskaryosis within five months . On colposcopy one of these women was found to have invasive cervical squamous cell carcinoma . It is concluded that whether women with inflammatory smears are treated or not, it is mandatory to repeat the smear, ideally within five months.

J Gen Microbiol, 1990 Jun, 136 ( Pt 6), 993 - 6
Lipids of Candida albicans: subcellular distribution and biosynthesis; Mago N et al.; Lipids constituted around 5% of the dry weight in Candida albicans 3153, while sterols and phospholipids accounted for 1.2% and 1.1% respectively . Phospholipids were mainly localized in the microsomal fraction; phosphatidylserine (PS), phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylinositol (PI) were the major phospholipids . Incorporation studies with {14C}acetate and {32P}orthophosphoric acid demonstrated that PS was synthesized at the highest rate followed by PC, PE and PI . There was little difference in either the content of the rate of biosynthesis of PC, PE and PI . Incorporation of labelled serine, ethanolamine and choline revealed serine to be a precursor for PC, PE and PS, ethanolamine for PC and PE, and choline for PC biosynthesis only.

J Immunol, 1990 Jun 1, 144(11), 4333 - 9
T cell subsets and IFN-gamma production in resistance to systemic candidosis in immunized mice; Cenci E et al.; In addition to previous evidence for the roles of T cell-dependent immunity and delayed-type hypersensitivity in acquired resistance to systemic candidosis in mice, in the present study we have investigated the relative contributions of L3T4+ and Lyt-2+ lymphocytes in the protective immunity induced by vaccination with low virulence Candida albicans cells . We have also addressed the issue of the mode of Candida Ag recognition by specific T cells leading to cytokine release . Spleen cells from immunized mice produced high levels of IFN-gamma in vitro in response to Candida Ag, and this activity was abolished only by the combined treatment of the responder population with anti-L3T4 and anti-Lyt-2.2 mAb plus C . Positively selected L3T4+ and Lyt-2+ cells also produced IFN-gamma in vitro, provided accessory cells (plastic-adherent and Thy-1- Ia- splenocytes, respectively) were added to the lymphocyte-yeast cell cocultures . The production of IFN-gamma by purified L3T4+ and Lyt-2+ cells was inhibited by addition of the respective anti-class II and anti-class I H-2 antibody to the cultures . In vivo, administration of anti-L3T4, anti-Lyt-2.2 mAb or a combination of both significantly impaired the resistance of immunized mice to challenge with virulent C . albicans, as manifested by increased recovery of the yeast from the mouse kidneys . A similar effect was observed upon neutralization of endogenous IFN-gamma by treatment with rat mAb . These results suggest that both L3T4+ and Lyt-2+ T cells play a role in acquired immunity to systemic C . albicans infection, and that their activity may involve IFN-gamma-mediated stimulation of candidacidal mechanisms.

Gene, 1990 May 31, 90(1), 115 - 23
Functional expression of the Candida albicans beta-tubulin gene in Saccharomyces cerevisiae; Smith HA et al.; Expression of the beta-tubulin-encoding gene (TUB2) of Candida albicans has been examined in Saccharomyces cerevisiae . Overexpression of the TUB2 gene of C . albicans, as well as that of S . cerevisiae, was found to be lethal . Chromosomal integration of the C . albicans TUB2 gene into a strain in which the native TUB2 gene had been deleted led to functional complementation . The results demonstrate that correct splicing of the two introns present in the C . albicans TUB2 gene occurs in the heterologous host strain containing this gene . Such strains are supersensitive to the tubulin-binding agent benomyl, indicating that the natural resistance of C . albicans to benomyl is not related to the structure of its beta-tubulin.

Chem Pharm Bull (Tokyo), 1990 May, 38(5), 1258 - 65
Synthesis and antifungal activities of some thiolane-triazole derivatives; Konosu T et al.; As part of our search for active agents against systemic fungal infections, a new series of triazole compounds with a thiolane ring was synthesized . Their antifungal activities were investigated in vitro and in vivo . Some of these thiolanetriazoles showed promising activity, comparable to that of ketoconazole, against a mouse systemic Candida albicans infection, after oral or parenteral dosing.

Z Hautkr, 1990 May, 65(5), 476 - 80
{Fungal involvement of the tongue and feces in dialysis-dependent patients}; Knoll R et al.; 38 patients regularly receiving dialysis and 3 patients with a renal transplant were investigated with regard to possible colonization of yeasts . The tongue and stool were directly examined with Kimmig agar, the resulting yeasts were then differentiated by means of rice agar and an auxanogram . Candida albicans was the germ most frequently found both on the tongue (47.5%) and in the stool (50%) . We discuss the significance of our results.

Eur J Clin Microbiol Infect Dis, 1990 May, 9(5), 352 - 5
Detection of an antibody response in immunocompetent patients with systemic candidiasis or Candida albicans colonisation; Porsius JC et al.; Tests to detect circulating antibodies to Candida albicans antigens were performed in sera from 27 immunocompetent patients, 15 of whom had deep-seated candidiasis and 12 of whom were colonised by Candida albicans . For the diagnosis of deep-seated candidiasis in patients with either deep-seated candidiasis or Candida albicans colonisation, counterimmunoelectrophoresis had a sensitivity of 87% and a specificity of 75% . Using immunoblotting it could be shown that antibodies to 35K, 47K, 68K and 88K antigens of Candida albicans occurred more frequently in patients with deep-seated candidiasis than in colonised patients . The presence of dense bands in immunoblots representing antibodies against the 47K and/or 68K antigen served to discriminate significantly between deep-seated and superficial candidiasis (p less than 0.05).

Mycopathologia, 1990 May, 110(2), 101 - 5
Fungal diarrhoea: association of different fungi and seasonal variation in their incidence; Talwar P et al.; A total of 854 patients (640 children and 214 adults) admitted with acute or chronic diarrhoea suspected of non-invasive overgrowth of fungi in intestine were screened during a period of 3 years . Fungal proliferation was noted in 54.8% of these patients (53.6% in children, 58.4% in adults) . The predominant fungal species isolated were Candida albicans (64.5%), followed by C . tropicalis (23.3%) C . krusei (6.9%) . Torulopsis glabrata (1.6%) . Trichosporon sp . and Geotrichum sp . were found to be responsible in 2.3% of adults . As seen in bacterial diarrhoea, higher incidence was noted in children from April to August . No such seasonal variation was noted in adults.

Neurosurgery, 1990 May, 26(5), 860 - 3
Cerebral granuloma and meningitis caused by Candida albicans: useful monitoring of mannan antigen in cerebrospinal fluid; Ikeda K et al.; The authors report the case of a previously healthy patient who had recurrent cerebral granulomas and meningitis caused by Candida albicans 15 years after the first onset . A combination of external drainage of cerebrospinal fluid (CSF) and intraventricular and intravenous chemotherapy with antifungal agents resulted in a favorable outcome . Investigation of this patient revealed no immunological dysfunction, lymphoproliferative disorder, or candidicidal defect of peripheral blood leukocytes . Sequential measurement of Candida mannan antigen in CSF was useful for establishing the early diagnosis of cerebral candidiasis and for judging the effect of our antifungal chemotherapy . In determining the surgical indications and timing of placement of a ventriculoperitoneal or ventriculoatrial shunt for meningitis subsequent to hydrocephalus after candidal infection, it is better to confirm normal concentrations of the mannan antigen in the CSF repeatedly for more than a week and to determine that cultures of the CSF are negative for Candida albicans.

Mycoses, 1990 May, 33(5), 253 - 5
Growth of Candida albicans on the stratum corneum of diabetic and non-diabetic patients; Rurangirwa A et al.; We have used a novel approach to in vitro culture of Candida albicans on cyanoacrylate skin surface strippings . It appears that with this model yeasts and hyphae grew on large surfaces of stratum corneum . The area of extension of the fungal growth was larger on stratum corneum taken from diabetic than from non-diabetic volunteers.

Mycoses, 1990 May, 33(5), 225 - 9
Molecular genetics of pathogenic fungi: some recent developments and perspectives; Ernst JF; The diagnosis and the treatment of fungal diseases remains problematic in many cases . Difficulties in diagnosis are due (1) to the ubiquitous presence of fungal pathogens that may lead to false positive test results and (2) to difficulties in the evaluation of the aetiological significance of these pathogens . The relatively small number of effective antifungal agents reflects to a large extent on the fact that many aspects of fungal physiology and virulence are not well understood . The methods of molecular genetics provide effective tools for the diagnosis of mycoses and may also contribute to the identification of new targets for antifungals by genetic analyses of fungal virulence . During the last 3 years molecular genetic methods have been developed for the asexual pathogen Candida albicans that may be used for strain identification . This success indicates a general use of molecular genetics for the analysis of fungal pathogenesis.

Am J Reprod Immunol, 1990 May, 23(1), 1 - 3
Humoral immunity to Candida albicans (anti-candida antibody titers) in premature infants; Katikaneni LD et al.; Although the role of humoral and cell mediated immunity in neonatal defense against candida infections is not precisely defined, one of the contributing immunologic factors may be a lack of decreased specific passive humoral immunity . Thus, serum samples from the umbilical veins of 98 term gestation and 105 premature neonates (majority less than 33 wk gestation) and their mothers (n = 100) were tested for the presence of hemagglutinating antibodies to commercially available candida antigen . The titers of candida antibodies (mean log2 +/- SEM) were significantly higher in 11 term neonates (4.73 +/- 0.69) of mothers with high antibody titers (5.18 +/- 0.40, less than 0.001) as contrasted with 87 normal term (2.38 +/- 0.15) and 105 premature (2.87 +/- 0.15) infants with normal mothers (1.96 +/- 0.13 and 3.31 +/- 0.26, respectively) . Contrary to our belief 81% of term infants and all of the preterm infants (majority less than 33 wk gestation) had passive specific anti-candida antibody titers less than 1:16.

Can J Microbiol, 1990 May, 36(5), 336 - 40
Equilibrium analysis of binding of Candida albicans to human buccal epithelial cells; Staddon W et al.; The effect of growth temperature on the binding of Candida albicans to human buccal epithelial cells (BECs) was examined using an equilibrium of binding analysis . Candida albicans was cultured in M9 medium either for 12 h at 25 degrees C or for 9 h at 25 degrees C and then shifted to 37 degrees C for 3 h . The temperature shift did not result in germ tube formation; however, the adherence of C . albicans to BECs was altered . Shifting temperature increased the yeast's ability to bind to BECs . A Langmuir adsorption isotherm was used to calculate the maximum number of available binding sites (N) and the apparent association constants of binding (Ka) for all resolvable adhesin-receptor interactions . Three classes of adhesin-receptor interactions were resolved when the yeast was cultured at 25 degrees C and included a low copy number site (N = 3.0 cfu/BEC; Ka = 2.11 X 10(-6) mL/cfu), a medium copy number site (N = 23.6 cfu/BEC, Ka = 8.21 X 10(-7) mL/cfu), and a high copy number site (N = 91.7 cfu/BEC, Ka = 3.35 X 10(-8) mL/cfu) . Two classes of adhesin-receptor interactions were resolved when the incubation temperature was shifted to 37 degrees C: a low copy number site (N = 4.5 cfu/BEC, Ka = 3.98 X 10(-6) mL/cfu) and a high copy number site (N = 150.5 cfu/BEC, Ka = 8.47 X 10(-8) mL/cfu) . Augmented C . albicans adherence to BECs due to the elevated growth temperatures appears to result from a temperature-regulated alteration in the C . albicans adhesin that recognizes a high copy number receptor site with relatively low affinity.

Arch Pharm (Weinheim), 1990 May, 323(5), 273 - 80
Researches on antibacterial and antifungal agents, XII: Analogues of bifonazole with two imidazole moieties and related azoles; Stefancich G et al.; Analogues of bifonazole bearing two imidazole rings and other related azoles have been synthesized and tested as antifungal agents against Candida albicans and Candida spp. . Only a slight part of the antifungal power of the parent drug is retained by some derivatives as evinced by the comparison of new compounds with bifonazole, miconazole, and ketoconazole.

FEMS Microbiol Lett, 1990 May, 57(1-2), 165 - 9
Pathways to acetyl-CoA formation in Candida albicans; Sheridan R et al.; The supply of acetyl units from the mitochondrion to the cytosol of Candida albicans appears to be dependent only upon the activity of carnitine acetyltransferase (CAT) . The enzyme ATP:citrate lyase (ACL), the major source of acetyl units in oleaginous yeasts, is absent from C . albicans in both the mycelial and yeast forms . There appears to be no other active translocation of acetate or acetyl groups except via the action of carnitine acetyltransferase.

Mycopathologia, 1990 May, 110(2), 63 - 76
Recombinagenicity of caffeine for Candida albicans; Sarachek A et al.; Caffeine at concentrations of 0.5 x 10(-2) M or higher inhibited cell replication and induced gene segregations in Candida albicans cultured on defined complete medium . Both responses increased incrementally with increasing caffeine concentrations, and were more severe during incubation at 37 degrees C than 25 degrees C; at 37 degrees C, caffeine levels above 1.5 x 10(-2) M caused cellular inactivation . Caffeine effects occurred only under conditions permitting cell growth, and their magnitudes were greater for unbudded than budding cells, were influenced by cellular genetic backgrounds, and were unaffected by the presence of adenine in the medium . Evaluations of segregations for recessive auxotrophic markers of a four member linkage group carried heterozygously in a cis arrangement in treated cells established that induced segregants arise through either reciprocal or nonreciprocal recombinations . The frequency distributions of classes of reciprocal and nonreciprocal recombinants for these markers conformed with those previously obtained following induction by ultraviolet radiation, indicating that the probabilities of recombinational events within the chromosomal regions defined by the markers are not biased by the differences in kinds of initial DNA lesions caused by the two recombinagens . A panel of four protoplast fusion hybrids considered deficient for DNA repair because of enhanced susceptibilities to UV induced cellular inactivation and mitotic recombination exhibited corresponding increased sensitivities to caffeine, signifying that DNA damage induced by caffeine is subject to repair . Caffeine did not affect behavior of a variant strain exhibiting high frequency phenotypic switching between minute smooth and large rough colonial forms, and no evidence for mutagenicity of the drug was obtained with systems for detection of forward or reverse mutations . The mechanism of caffeine's recombinagenicity, and the implications of that property for genetic studies of C . albicans are discussed.

Clin Exp Dermatol, 1990 May, 15(3), 183 - 91
Characterization of Candida albicans epidermolytic proteases and their role in yeast-cell adherence to keratinocytes; el-Maghrabi EA et al.; Epidermolytic proteases were partially purified from six strains of Candida albicans, four of which were isolated from patients with cutaneous diseases . Two of the strains exhibited a unique time-course of enzyme production compared to that previously reported, with detectable epidermolytic protease levels being significantly delayed . All epidermolytic proteases had pH and temperature optima of 4-4.5 and 35-37 degrees C, respectively . These conditions are consistent with the microenvironment of human skin, a habitat where an epidermolytic protease would appear to be an important advantage to the yeast . Candida epidermolytic proteases were more active against a substrate of normal human epidermis than that obtained from psoriatic patients . When human epidermis replaced bovine serum albumin as the protein source within the culture medium, the epidermolytic activity of the resultant enzyme was reduced by 9 and 25% for normal and psoriatic epidermis substrates, respectively . The proteases were found to contain major protein bands at 42 and 66 kDa . The ability of these same Candida strains to adhere to human epidermal cells was studied and found to be optimal at 35-37 degrees C within neutral pH values . Pepstatin, bovine brain gangliosides, and convalescent human serum all interfered with the adherence of the yeast to epidermal cells . A higher yeast-epidermal-cell adherence for Candida was demonstrated on normal rather than psoriatic epidermal cells, and after treating the cells with partially purified Candida protease.

Antimicrob Agents Chemother, 1990 May, 34(5), 831 - 6
Azole susceptibility and hyphal formation in a cytochrome P-450-deficient mutant of Candida albicans; Lees ND et al.; A cytochrome P-450-deficient mutant of Candida albicans, strain D10, was employed to study the mode of action of imidazole antifungal agents . This mutant accumulates exclusively 14-alpha-methylsterols, resulting in a sterol profile which mimics that of azole-treated wild-type strains . Since the widely accepted primary effect of imidazoles is the inhibition of cytochrome P-450-mediated demethylation of the ergosterol precursor lanosterol, strain D10 and its wild-type revertant, strain D10R, were grown in the presence of concentrations of clotrimazole, miconazole, and ketoconazole known to inhibit demethylation . The growth of strain D10 was unaffected by these antifungal agents, while that of strain D10R was significantly reduced . At higher azole concentrations (which are known to exert a direct, disruptive action on the cell membrane), the growth of both strains was immediately and completely inhibited by clotrimazole and miconazole . Ketoconazole was membrane disruptive only for strain D10; this is the first report of a direct membrane effect for this drug . Because hyphal formation has been implicated in the pathogenesis of C . albicans and because it has been shown to be inhibited by azoles, the hypha-forming capability of strain D10 was examined . Strain D10 was shown to be seriously defective in hyphal formation, suggesting that this function may be dependent on the 14-alpha-demethylation of lanosterol . The results of this study suggest that inhibition of lanosterol demethylation per se is neither fungicidal nor fungistatic, although the growth rate is reduced . In addition, the substitution of 14-alpha-methylsterols for ergosterol results in defective hyphal formation and in a cell that is more susceptible to membrane-active agents such as ketoconazole.

Antimicrob Agents Chemother, 1990 May, 34(5), 746 - 50
Comparative effects of cilofungin and amphotericin B on experimental murine candidiasis; Morrison CJ et al.; The effectiveness of cilofungin (LY121019, referred to hereafter as LY), a lipopeptide, was studied in a murine candidiasis model . CD-1 mice (5 weeks old) were injected intravenously with 3 x 10(5) Candida albicans yeast cells . Intraperitoneal LY or amphotericin B (AmB) therapy was begun 4 days after infection and was continued daily for 2 weeks . LY and AmB were compared at 62.5, 6.25, and 0.625 mg/kg per day, with the LY dose split into two treatments per day . Mice were observed for 30 days postinfection, and survivors were necropsied . AmB at 62.5 mg/kg per day was lethal in the absence of infection . Cumulative mortality for infected controls was 94% (17 of 18) . Survival of mice treated with the control diluent for LY was the same as survival with no treatment . Survival after 0.625 mg of LY per kg per day was the same as that of the controls, and 6.25 or 62.5 mg of LY per kg per day was significantly superior . AmB treatment at 0.625 or 6.25 mg/kg per day was protective and superior to the same LY doses . Atrophied kidneys were common in AmB-treated mice, and mice treated with 6.25 mg of AmB per kg per day appeared ill during therapy . The number of CFU recovered from kidneys and spleens of surviving mice reflected the same relationships between drugs and doses as those described for mortality . C . albicans was not cleared from the kidneys of mice in any group, and only in the 6.25-mg/kg-per-day AmB treatment group was not detectable C . albicans found in the spleens . These data indicate that LY or AmB suppresses candida infection but neither is curative in this model.

J Clin Microbiol, 1990 May, 28(5), 876 - 81
Electrophoretic karyotyping of typical and atypical Candida albicans; Mahrous M et al.; Electrophoretic karyotypes of atypical isolates of Candida albicans, e.g., strains that were germ tube negative, failed to express proteinase activity, demonstrated low virulence for mice, formed hyperchlamydoconidia, produced hyperhyphae, or were sucrose negative (including the type strain of Candida stellatoidea), were compared with those of typical C . albicans . Karyotypes of whole-cell DNA of classical C . albicans examined with transverse alternating-field electrophoresis under specific conditions were composed of seven DNA bands with a specific migration pattern . Certain atypical strains and representatives of the three serotypes of C . stellatoidea produced discrete karyotypes with 5 to 10 bands . All isolates demonstrated a significant degree of DNA relatedness, suggesting their conspecificity . Densitometric tracings of DNA bands provided an objective and standardized method for comparing bands within the gels.

Gut, 1990 May, 31(5), 536 - 8
Antibody to selected strains of Saccharomyces cerevisiae (baker's and brewer's yeast) and Candida albicans in Crohn's disease; McKenzie H et al.; IgG serum antibody was measured by ELISA in patients with Crohn's disease (15), ulcerative colitis (15), and in normal controls (15) to 12 strains of Saccharomyces cerevisiae (baker's and brewer's yeast) and to the two major serotypes of the commensal yeast Candida albicans . Antibody to 11 of the 12 strains of S cerevisiae was raised in patients with Crohn's disease but not in patients with ulcerative colitis when compared with controls (p less than 0.001) . The pattern of antibody response to these 11 strains was variable, however, suggesting the likelihood of antigenic heterogeneity within the species . Antibody to C albicans was not significantly different in patient and control groups . The specificity of this unusual antibody response in Crohn's disease for S cerevisiae suggests that it is not simply the result of a generalised increase in intestinal permeability . Furthermore, because brewing and baking strains detected the response, the relevant antigen(s) are presumably common in the diet . Hypersensitivity to dietary antigens may be involved in the pathogenesis of Crohn's disease, and the role of S cerevisiae requires further investigation.

Ophthalmology, 1990 May, 97(5), 666 - 72; disc: 672-4
Endogenous Candida endophthalmitis . Management without intravenous amphotericin B; Brod RD et al.; Eight consecutive cases of culture-proven endogenous Candida endophthalmitis (ECE) were managed between 1980 and 1988 . All patients were treated with vitrectomy and injection of intravitreal amphotericin B . Blood cultures were negative in all patients, although Candida albicans was cultured from a foot ulcer in one patient . No systemic therapy was used in three patients, three patients received oral ketoconazole, and two patients received oral flucytosine postoperatively . Intravenous amphotericin B was not used because of lack of evidence of disseminated candidiasis and the systemic toxicity associated with its use . The ECE responded favorably to treatment in all cases . Final vision was better in patients with a shorter interval between onset of symptoms and initiation of antifungal therapy . Posttreatment visual acuities were: four eyes greater than or equal to 20/50, two eyes at 20/80 to 20/200, and two eyes less than 5/200 . This series showed that ECE without evidence of disseminated disease can be treated successfully with vitrectomy and intravitreal amphotericin B.

J Bacteriol, 1990 May, 172(5), 2384 - 91
Isolation and characterization of Candida albicans morphological mutants derepressed for the formation of filamentous hypha-type structures; Gil C et al.; Several Candida albicans morphological mutants were obtained by a procedure based on a combined treatment with nitrous acid plus UV irradiation and a double-enrichment step to increase the proportion of mutants growing as long filamentous structures . Altered cell morphogenesis in these mutants correlated with an altered colonial phenotype . Two of these mutants, C . albicans NEL102 and NEL103, were selected and characterized . Mutant blastoconidia initiated budding but eventually gave rise to filamentous hypha-type formations . These filaments were long and septate, and they branched very regularly at positions near septa . Calcofluor white (which is known to bind chitin-rich areas) stained septa, branching zones, and filament tips very intensely, as observed under the fluorescence microscope . Wild-type hybrids were obtained by fusing protoplasts of strain NEL102 with B14, another morphological mutant previously described as being permanently pseudomycelial, indicating that genetic determinants responsible for the two altered phenotypes are different . The mutants characterized in this work seemed to sequentially express the morphogenic characteristics of C . albicans, from blastoconidia to hyphae, in the absence of any inducer . Further characterization of these strains could be relevant to gain understanding of the genetic control of dimorphism in this species.

J Antimicrob Chemother, 1990 May, 25(5), 803 - 11
Effect of amphotericin B, fluconazole and itraconazole on intracellular Candida albicans and germ tube development in macrophages; Van 't Wout JW et al.; Candida albicans may resist intracellular killing by macrophages through the formation of germ tubes . Antifungal drugs that inhibit intracellular germ tube formation could therefore facilitate host defence against C . albicans . We assessed the effects of amphotericin B and the new triazole drugs fluconazole and itraconazole on the multiplication and intracellular germ tube formation of C . albicans phagocytosed by murine peritoneal macrophages, and compared the findings with the effects of these drugs on C . albicans in the absence of macrophages . The fungicidal effect of amphotericin B against C . albicans in macrophages was less prominent than that found for extracellular candida . However, amphotericin B completely blocked germ tube formation of C . albicans both in macrophages and extracellularly . Fluconazole and itraconazole had little effect on the number of candida but significantly, although incompletely, inhibited germ tube formation both inside macrophages and extracellularly . The inhibition of intracellular germ tube formation by the triazoles may facilitate host defences against C . albicans and contribute to the efficacies of these drugs in vivo.

J Infect Dis, 1990 May, 161(5), 999 - 1005
Granulocyte-macrophage colony-stimulating factor augments human monocyte fungicidal activity for Candida albicans; Smith PD et al.; The ability of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) to augment the fungicidal activity of human monocytes for Candida albicans was evaluated . Purified human monocytes cultured with {3H}leucine-labeled C . albicans caused a dose-dependent release of the {3H}leucine . The amount of {3H}leucine released correlated with a decrease in the number of viable yeast colonies . Monocyte cytotoxicity for C . albicans was reduced by superoxide dismutase and catalase and by inhibitors of myeloperoxidase and scavengers of hydroxyl radical and single oxygen, consistent with monocyte candidacidal activity being partly dependent upon products of oxidative metabolism . Monocytes incubated with rhGM-CSF produced more superoxide anion (O2-) spontaneously and after stimulation than control monocytes (P less than .05) . Enhanced O2- production was dose-dependent and specific for rhGM-CSF and could be inhibited by antibody to rhGM-CSF . In association with rhGM-CSF-induced production of O2-, the cytokine enhanced cytotoxic activity for C . albicans . These findings indicate that rhGM-CSF stimulates human monocyte fungicidal activity for C . albicans.

Infect Immun, 1990 May, 58(5), 1174 - 9
Effects of neutrophils and in vitro oxidants on survival and phenotypic switching of Candida albicans WO-1; Kolotila MP et al.; The relationship to pathogenesis of the spontaneous phenotypic switching of Candida albicans is uncertain . Since neutrophils are critical in containment of disseminated candidiasis, we used these cells and some of their potentially microbicidal oxidative products to define effects on a C . albicans strain (WO-1) that exhibits characteristic, easily recognized switching between the white and opaque phenotypes . Blastoconidia of the opaque phenotypes were more susceptible than those of the white to killing by either intact neutrophils or cell-free oxidants, including reagent hydrogen peroxide or the myeloperoxidase-H2O2-Cl- system . Paralleling these findings, opaque blastoconidia were 2.8- to 3.6-fold more potent stimuli of neutrophil superoxide generation than were the white cells . In addition, both neutrophils and oxidants (reagent H2O2 or hypochlorous acid as well as the myeloperoxidase-H2O2-Cl- system) induced unidirectional increases in spontaneous rates of switching from white to opaque phenotypes . Differences in expression of C . albicans phenotypes therefore may determine relative susceptibility to neutrophil fungicidal mechanisms, and neutrophils themselves appear to be capable of selectively augmenting the switching process.

Prostaglandins Leukot Essent Fatty Acids, 1990 May, 40(1), 31 - 8
Phospholipase A2, an in vivo immunomodulator; Bravo Cuellar A et al.; Arachidonic acid (AA) can be released from membrane phospholipids by the action of phospholipase A2 (PLA2) . There is evidence that unsaturated fatty acids, particularly AA, released from membrane phospholipids are required to activate the respiratory burst of macrophages . The data reported here indicate that peritoneal macrophages harvested 30 min after i.p . injection of PLA2 can phagocytose Candida albicans more efficiently and emit more chemoluminescence (CL) than normal cells when stimulated by zymosan . PLA2 injection also enhances the CL of peritoneal cells from mice already stimulated by immunomodulators such as trehalose dimycolate (TDM), bestatin, or oncostatic drugs such as aclacinomycin (ACM) . CL is not sensitive to potassium cyanide (KCN), but is inhibited by catalase, superoxide dismutase (SOD), nordihydroguaiaretic acid (NDGA) and high doses of indomethacin (10(-3) M) . In vivo PLA2 treatment stimulates the synthesis of both cyclooxygenase and lipoxygenase derivatives of AA metabolism (PGE2, 6-keto, PGF1 alpha TXB2 and LTC4) . Inhibitors of AA metabolism (NDGA, indomethacin) modulate the production of free oxidizing radicals in this experimental model, partly because of their effect on AA metabolism, as determined by the measuring immunoreactive products . However, this work indicates that the effects of these inhibitors, which have been extensively used in CL studies, should be interpreted with caution, since their specificity for AA metabolism is relative.

Parodontol, 1990 May, 1(2), 119 - 32
{HIV-associated periodontal lesions}; Langford A; During HIV infection different lesions may occur in the area of the gingiva and/or the periodontium . An increased frequency and severity of periodontal diseases has been observed . Different forms of Candida albicans infection have been clinically characterized as pseudomembranous, erythematous (atrophic) or hyperplastic form or as papillary variant . While infection with Candida albicans may occur frequently in other areas of the oral mucosa, candidiasis of the gingiva seems to be quite rare . Due to the underlying immunodeficiency, HIV-infected patients are prone to infection with and/or reactivation of different viruses, which may cause oral lesions as well . Recurrent progressive ulcerations may occur due to herpes simplex virus 1/2, while ulcerations with a punched-out appearance may result from disseminated CMV infection . Oral Kaposi's sarcoma may clinically present as bluish or red spots, which may increase into exophytic tumors during the progress of the disease.

Paediatr Indones, 1990 May-Jun, 30(5-6), 133 - 8
Spectrum of digestive tract diseases 1985-1987 at the Pediatric Gastroenterology Outpatient Clinic of Dr . Pirngadi General Hospital, Medan; Siregar CD et al.; A retrospective study has been done on infants and children attending to the Pediatric Gastroenterology Outpatient Clinic of Dr . Pirngadi General Hospital in Medan, from 1985 through 1987 . During the study there were 874 patients, 477 (54.58%) suffered from diarrhea, 209 (23.91%) had bloody stool, 20 (2.99%) jaundice, 57 (6.52%) abdominal pain, 48 (5.49%) abdominal distention, 30 (3.43%) vomiting, 13 (1.49%) constipation, and 20 (2.29%) others . Of all cases with diarrhoea, watery diarrhoea were found in only 319 (66.88%), diarrhoea with vomiting 84 (17.61%), and bloody diarrhoea 74 (15.51%) . Stool examination in patients with diarrhoea revealed 144 (30.19%) cases with Candida albicans, while 16 (3.35%) of them with steatorrhoea . Of 63 patients with diarrhoea on which the clinitest had been performed, sugar intolerance were found in 30 (47.62%) cases.

Br Dent J, 1990 Apr 21, 168(8), 326 - 9
Alteration of humoral responses to Candida in HIV infection; Wray D et al.; The objectives of this preliminary study were to determine the prevalence of oral candidal carriage and infection in a group of HIV-positive individuals and compare the humoral immune responses in serum and saliva in this group with a control group of HIV-negative subjects . Patients were examined clinically with particular reference to the presence of candidal lesions and oral swabs taken to identify carriers . Venous blood and whole saliva were obtained for estimation of total and anti-Candida antibody levels . Pseudomembranous candidiasis was the commonest clinical variant in HIV-positive individuals . Candida albicans was the commonest species isolated in both groups . Increased levels of anti-Candida IgG were found in both serum and saliva of HIV-negative individuals who were either carriers of Candida species or had clinical candidiasis . This was associated with a reciprocal fall in anti-Candida IgA . Similar trends were seen in HIV-positive individuals in association with candidal carriage and infection, although the changes were more marked.

J Surg Res, 1990 Apr, 48(4), 308 - 12
Variable infection risk following allogeneic blood transfusions; Brunson ME et al.; These studies address infection risk of allogeneic transfusion in an untraumatized, nonseptic rodent model . A' Segaloff Cancer Institute rats served as blood donors and Lewis rats as recipients . Lewis rats' delayed-type hypersensitivity (DTH) response and their ability to clear subdermal Staphylococcus aureus abscesses and Candida albicans pyelonephritis were measured as tests of the effect of transfusions . The effect of pharmacological immunosuppression with either cortisone acetate or cyclosporine provided a "yardstick" to measure the magnitude of transfusion effects . Repeated transfusions at 1-week intervals diminished DTH response to recall antigens (keyhole limpet hemocyanin), but otherwise they showed no evidence of immunosuppression in these experiments . In contrast, we found that transfusions by themselves produced mild immunostimulation . Subcutaneous Staphylococcus abscesses were smaller in animals receiving transfusions . The magnitude of immunostimulation from one transfusion was sufficient to reverse the immunosuppressive effect of cyclosporine by about 50% in a Candida pyelonephritis infection . These studies suggest that blood transfusions have complex interactions with different components of the immune response . T-cell function is impaired by repeated transfusions (diminished DTH response), but other inflammatory responses are accentuated . This suggests that blood transfusions may harm immune response in traumatized animals by causing excessive complement activation or cytokine release.

Am J Gastroenterol, 1990 Apr, 85(4), 428 - 34
Persistent immune deficiency in patients with alcoholic hepatitis; Mutchnick MG et al.; T-lymphocyte subset numbers, recall-antigen skin test responses and mitogen-induced lymphocyte proliferation assays were investigated in 12 patients with severe alcoholic hepatitis (AH) . Serial studies of these parameters were obtained at intervals of 1 or 2 wk . Patients with AH had lower peripheral blood lymphocyte counts with corresponding decreases in T-cell subset numbers that were persistent in the serial evaluations . T8 cells were disproportionately decreased, with a significant resultant increase in the T4:T8 ratios . Compared with controls, AH patients had significantly smaller cutaneous responses to Candida albicans antigen (p less than 0.05) and mumps antigen (p less than 0.005) . Fifty-eight percent of patients were anergic when tested with a battery of four antigens . Patients with AH had increased concanavalin A-, but not phytohemagglutinin-induced lymphocyte proliferative responses . These serial analyses confirm previous observations of cell-mediated immune dysfunction in patients with severe AH . Moreover, there is a persistence of these abnormalities for at least 6 wk after withdrawal from alcohol.

Mycoses, 1990 Apr, 33(4), 191 - 202
Rilopirox--a new hydroxypyridone antifungal with fungicidal properties; Raether W et al.; Rilopirox, 6-{{p-chlorophenoxy)phenoxy}methyl}-1hydroxy-4-methyl-2(1H)-pyrido ne, is a new fungicidal antimycotic with very low water solubility . It was designed to meet the demand for an intravaginal antifungal with a long skin retention time and a strong killing effect on pathogenic yeasts . In addition, it inhibits all common fungal pathogens in the range 0.98 to 15.6 micrograms/ml . Fungicidal rates vis-a-vis Trichophyton mentagrophytes and Candida albicans under proliferative and non-proliferative conditions are higher than those achieved with common azole and allylamine antifungals . Rilopirox is affected by Fe3+ ions and high concentrations of human serum owing to its chelating activity . The peptone source is of utmost importance to the inhibitory activity of rilopirox whereas the pH value seems to be unimportant so long as it is within the range 5-8.5 . Rilopirox appears to meet the demand for an intravaginal antifungal as a result of its very low water solubility of 50 ng/ml and its immediate fungicidal action even under non-proliferative conditions.

J Gen Microbiol, 1990 Apr, 136 ( Pt 4), 687 - 94
The secreted aspartate proteinase of Candida albicans: physiology of secretion and virulence of a proteinase-deficient mutant; Ross IK et al.; It was established that Candida albicans grew rapidly in a simple medium containing yeast extract (0.2%, w/v) plus glucose (2%, w/v) . These cultures were in or near to a state of nitrogen limitation and the concentration of secreted aspartate proteinase increased rapidly (within 3-4 h) on addition of BSA . Synthesis and secretion were apparently controlled both positively (induction by albumin or, more probably, the peptides produced from it) and negatively (repression by NH4Cl) . A small intracellular pool of the enzyme was detected during production of the enzyme and this pool decreased with the cessation of synthesis and secretion . A stable mutant, IR24, was isolated which secreted less than 0.3% of the amount of the proteinase exported by the parent strain ATCC 10261 . The LD50 values for mutant IR24 and the parent strain administered intravenously to mice were greater than 1.0 x 10(9) and 1.6 x 10(6) c.f.u . kg-1 respectively.

Mol Gen Genet, 1990 Apr, 221(2), 210 - 8
Isolation and nucleotide sequence of an autonomously replicating sequence (ARS) element functional in Candida albicans and Saccharomyces cerevisiae; Cannon RD et al.; An 8.6-kb fragment was isolated from an EcoRI digest of Candida albicans ATCC 10261 genomic DNA which conferred the property of autonomous replication in Saccharomyces cervisiae on the otherwise non-replicative plasmid pMK155 (5.6 kb) . The DNA responsible for the replicative function was subcloned as a 1.2-kb fragment onto a non-replicative plasmid (pRC3915) containing the C . albicans URA3 and LEU2 genes to form plasmid pRC3920 . This plasmid was capable of autonomous replication in both S . cerevisiae and C . albicans and transformed S . cerevisiae AH22 (leu2-) to Leu+ at a frequency of 2.15 x 10(3) transformants per microgram DNA, and transformed C . albicans SGY-243 (delta ura3) to Ura+ at a frequency of 1.91 x 10(3) transformants per microgram DNA . Sequence analysis of the cloned DNA revealed the presence of two identical regions of eleven base pairs (5'TTTTATGTTTT3') which agreed with the consensus of autonomously replicating sequence (ARS) cores functional in S . cerevisiae . In addition there were two 10/11 and numerous 9/11 matches to the core consensus . The two 11/11 matches to the consensus, CaARS1 and CaARS2, were located on opposite strands in a non-coding AT-rich region and were separated by 107 bp . Also present on the C . albicans DNA, 538 bp from the ARS cores, was a gene for 5S rRNA which showed sequence homology with several other yeast 5S rRNA genes.(ABSTRACT TRUNCATED AT 250 WORDS)

Burns, 1990 Apr, 16(2), 105 - 8
Effect of intraluminal antibiotics on translocation of Candida albicans in burned guinea-pigs; Epstein MD et al.; Guinea-pigs were pretreated orally with various antibiotics and given 3 x 10(10) Candida albicans by gastric lavage followed by a 40 per cent TBSA full skin thickness burn . The mesenteric lymph nodes, liver and spleen were cultured for the presence of viable organisms . Caecal contents were quantitatively cultured for aerobic bacteria and C . albicans . Clindamycin and penicillin G were the greatest promoters of translocation followed by the combination streptomycin/bacitracin . The mechanism for antibiotic-induced translocation is multifactorial centering on intestinal flora, anaerobic spectrum of the antibiotic and host defense as well as microbe virulence . The systemic use of broad-spectrum antibiotics, particularly those with strong anaerobic activity, should not be taken too lightly . A severely immunocompromised patient on this type of therapy may be prone to a severe fungal infection . This study reaffirms the concept that translocation from the gastrointestinal barrier is a potential source of life-threatening nosocomial infection.

Curr Genet, 1990 Apr, 17(4), 293 - 6
The isolation of osmotic-remedial conditional lethal mutants of Candida albicans; Payton MA et al.; We have developed a method for the isolation of a broad range of conditional lethal mutants of the pathogenic fungus Candida albicans . The method substantially alleviates the problems posed by the diploid nature, and the biased mutant spectrum, exhibited by most strains of this organism . We have used the method to isolate 560 temperature-sensitive mutants which grew at 30 degrees C but not at 42 degrees C . We identified amongst them a number of osmotic-remedial strains which, at the restrictive temperature, show phenotypes indicating defects in cell wall biosynthesis.

J Prosthet Dent, 1990 Apr, 63(4), 437 - 43
An in vivo replica method for the site-specific detection of Candida albicans on the denture surface in denture stomatitis patients: correlation with clinical disease; Santarpia RP 3rd et al.; A site-specific agar replica technique for detecting Candida albicans on the acrylic resin denture surface of denture stomatitis patients has been developed . The method is selective for C . albicans during a finite incubation period with a specific synthetic growth medium . C . albicans colonies can be geographically observed on the replica and their presence can be correlated with inflammatory lesions visible on the mucosa of the maxillary and mandibular residual ridges . In 12 denture stomatitis patients studied, a close clinical correlation of Newton type III patients was noted but this clinical correlation could not be observed in Newton type I and II patients . In general, the number of C . albicans colonies increased with the severity of the inflammation . The findings are discussed in light of lack of knowledge of the etiology of the stomatitis . The importance of the replica method is also discussed.

Arch Biochem Biophys, 1990 Apr, 278(1), 195 - 204
Structural study of cell wall phosphomannan of Candida albicans NIH B-792 (serotype B) strain, with special reference to 1H and 13C NMR analyses of acid-labile oligomannosyl residues; Kobayashi H et al.; Chemical structures of manno-oligosaccharides, from biose to heptaose, released from the phosphomannan of Candida albicans NIH B-792 strain (serotype B) by mild acid hydrolysis were investigated . The results of 1H NMR, 13C NMR, and fast atom bombardment mass spectrometry analyses confirmed that these manno-oligosaccharides belong to a homologous beta-1,2-linked series . Although chemical shifts of 1H NMR patterns of these oligosaccharides were considerably too complicated to be assigned, their 13C NMR patterns were sufficiently simple to be interpreted, exhibiting a regular increase of downfield shift of ppm values of the C-1 atom from each mannopyranose residue in proportion to their molecular weights . In order to determine the whole chemical structure of the parent phosphomannan, the acid-stable domain was subjected to acetolysis and then enzymolysis with the Arthrobacter GJM-1 alpha-mannosidase and the resultant manno-oligosaccharides were investigated for their chemical structures by 1H NMR spectroscopy . The results of a precipitin-inhibition test using the beta-1,2-linked manno-oligosaccharides, from biose to hexaose, in comparison with the corresponding isomers containing alpha-1,2 linkage with small amounts of alpha-1,3 linkage, indicated that the haptens possessing the former linkage exhibited much higher inhibitory effects than the corresponding isomers containing the latter linkages did . Based on the present findings, a chemical structure of the phosphomannan of this C . albicans strain was proposed.

J Bacteriol, 1990 Apr, 172(4), 2036 - 45
Sequence analysis and expression of the two genes for elongation factor 1 alpha from the dimorphic yeast Candida albicans; Sundstrom P et al.; Two Candida albicans genes that encode the protein synthesis factor elongation factor 1 alpha (EF-1 alpha) were cloned by using a heterologous TEF1 probe from Mucor racemosus to screen libraries of C . albicans genomic DNA . Sequence analysis of the two clones showed that regions of DNA flanking the coding regions of the two genes were not homologous, verifying the presence of two genes, called TEF1 and TEF2, for EF-1 alpha in C . albicans . The coding regions of TEF1 and TEF2 differed by only five nucleotides and encoded identical EF-1 alpha proteins of 458 amino acids . Both genes were transcribed into mRNA in vivo, as shown by hybridization of oligonucleotide probes, which bound specifically to the 3' nontranslated regions of TEF1 and TEF2, respectively, to C . albicans total RNA in Northern (RNA) blot analysis . The predicted EF-1 alpha protein of C . albicans was more similar to Saccharomyces cerevisiae EF-1 alpha than to M . racemosus EF-1 alpha . Furthermore, codon bias and the promoter and termination signals of the C . albicans EF-1 alpha proteins were remarkably similar to those of S . cerevisiae EF-1 alpha . Taken together, these results suggest that C . albicans is more closely related to the ascomycete S . cerevisiae than to the zygomycete M . racemosus.

Infect Immun, 1990 Apr, 58(4), 1093 - 100
Mucosal and systemic candidiasis in congenitally immunodeficient mice; Cantorna MT et al.; Colony counts and light microscopy were used to assess the capacity of Candida albicans to colonize, infect the alimentary tract, and cause disseminated disease in athymic (nu/nu), euthymic (nu/+), beige (bg/bg), black (bg/+), beige athymic (bg/bg nu/nu), or beige euthymic (bg/bg nu/+) germfree mice . The alimentary tracts of all six genotypes of germfree mice were quickly colonized after exposure to yeast-phase C . albicans . Only bg/bg nu/nu mice showed obvious morbidity and mortality after mucosal colonization with C . albicans . Histopathology of C . albicans-colonized immunocompetent (nu/+, bg/+) and singly immunodeficient (nu/nu, bg/bg, bg/bg nu/+) mice showed minimal to moderate mucosal infections, whereas doubly immunodeficient (bg/bg nu/nu) mice showed extensive yeast and hyphal infection of the palate, tongue, esophagus, and stomach . A progressive systemic infection in C . albicans-colonized mice occurred only in bg/bg nu/nu mice 12 to 16 weeks after colonization and mucosal infection . Thus, it appears that a combination of defective cell-mediated immunity and phagocytic cell defects (polymorphonuclear leukocytes and/or macrophages) predisposed mice to severe mucosal and systemic candidiasis of endogenous origin . This is the first report of a mouse strain that is not only naturally susceptible to mucosal and systemic candidiasis of endogenous origin but also shows lethality at early (1 to 4 weeks) and late (12 to 16 weeks) times after alimentary tract colonization.

Can J Microbiol, 1990 Apr, 36(4), 249 - 53
Carbon dioxide induces endotrophic germ tube formation in Candida albicans; Mock RC et al.; Candida albicans formed germ tubes when exposed to air containing 5 to 15% carbon dioxide (CO2) . The CO2-mediated germ tube formation occurred optimally at 37 degrees C in a pH range of 5.5 to 6.5 . No germ tubes were produced at 25 degrees C, even when the optimal concentration of CO2 (10%) was present in the environment . The requirement of CO2 for germ tube formation could be partially substituted by sodium bicarbonate but not by N2 . Carbon dioxide was required to be present throughout the entire course of germ tube emergence suggesting that its role is not limited to an initial triggering of morphogenic change . We suggest that carbon dioxide may be a common effector responsible for the germ tube promoting activity of certain chemical inducers for C . albicans.

Infect Immun, 1990 Apr, 58(4), 909 - 13
Reduced expression of the functionally active complement receptor for iC3b but not for C3d on an avirulent mutant of Candida albicans; Ollert MW et al.; Pseudohyphae of Candida albicans bear surface receptors for iC3b and C3d . In order to determine a possible role for these receptors in the pathogenesis of candidiasis, a spontaneous C . albicans mutant, m-10, which exhibits reduced ability to adhere in vitro to fibrin platelet clots and epithelial cells or to cause endocarditis in a rabbit model, and its parent wild-type (wt) strain were compared for receptor expression in rosetting assays with sheep erythrocytes carrying iC3b (EAC1423bi) or C3d (EAC1423d) . An equally high attachment to wt and m-10 was seen with EAC1423d, whereas rosetting with EAC1423bi was reduced by 53% in m-10 compared with wt . In inhibition studies, rosetting of wt with EAC1423bi was markedly inhibited by culture filtrate, hyphal-cell extract, and DEAE-fractionated material prepared from wt (54, 87, and 70% decreases in rosetting, respectively), thus suggesting the presence of the soluble, functionally active iC3b receptor of C . albicans in each of these preparations . Minimal inhibition of iC3b rosetting, however, was seen with the identical materials from m-10 (21, 5, and 12%, respectively) . All of the preparations from the two strains were equally effective in their inhibitory activities against rosetting of C3d . A human serum specimen obtained from a patient with chronic mucocutaneous candidiasis blocked iC3b rosetting of the wt strain almost completely . When used in an immunoblot, this serum recognized proteins of 68 to 71, 55, and 50 kilodaltons (kDa) in hyphal-cell extracts of the wt . With the same preparation of the avirulent mutant, only weak reactions with the 68- to 71-kDa and 55-kDa proteins occurred, while the 50-kDa protein was not detectable . Taken together, these results indicate that the expression of the functionally active iC3b receptor on C . albicans may be involved in the virulence of the organism, possibly by mediating adherence to mammalian cells.

Mycoses, 1990 Apr, 33(4), 173 - 8
In vitro and in vivo activity of antifungal agents in combination with fleroxacin, a new quinolone; Polak A; The in vitro and in vivo interaction of fleroxacin with amphotericin B (Amph B), flucytosine (5-FC) and azoles against Candida albicans strains was tested . In vitro the interaction between fleroxacin and various antifungals was not dependent on the incubation time . Fleroxacin neither enhances nor antagonizes the in vitro activity of Amph B at high concentration (50-100 micrograms/ml) . Fleroxacin has a synergistic effect with ketoconazole (KETO), but this is not observed with itraconazole (ITRA) or fluconazole (FLU) . In no instance antagonism was observed . The activity of 5-FC was antagonized by fleroxacin being generally reduced by 2-4 dilution steps . In murine candidosis the efficacies of all antifungal drugs were not influenced by addition of 100 mg/kg fleroxacin . Therefore, the effects seen in in vitro tests are most probably not relevant for the clinical use of a combination of fleroxacin with antifungal drugs.

Infect Immun, 1990 Apr, 58(4), 1073 - 7
Augmentation of GG2EE macrophage cell line-mediated anti-Candida activity by gamma interferon, tumor necrosis factor, and interleukin-1; Blasi E et al.; The expression of anti-Candida activity in the GG2EE macrophage cell line, generated by immortalization of fresh bone marrow with v-raf and v-myc oncogenes, was studied . GG2EE cells spontaneously inhibited the growth of an agerminative mutant of Candida albicans in vitro . The anti-Candida activity was maximal after 8 h of coculture and was proportional to the effector-to-target ratio . Gamma interferon (IFN-gamma), interleukin-1 (IL-1), and tumor necrosis factor (TNF) all significantly enhanced the anti-Candida activity of GG2EE cells . In contrast, IL-3, IL-4, and colony-stimulating factor 1 were ineffective . The augmentation of anti-Candida activity was not always concomitant with enhancement of phagocytosis, since IFN-gamma and colony-stimulating factor 1, but not IL-1 or TNF, augmented the phagocytic ability of GG2EE cells . Furthermore, the augmentation of anti-Candida activity in GG2EE cells did not correlate with the acquisition of antitumor activity . In fact, none of the cytokines alone were able to induce antitumor activity in GG2EE cells, which, however, could be activated to a tumoricidal stage by IFN-gamma plus heat-killed Listeria monocytogenes . These findings demonstrate that GG2EE cells exhibit spontaneous anti-Candida activity and that such activity is enhanced by TNF, IL-1, and IFN-gamma.

Oral Microbiol Immunol, 1990 Apr, 5(2), 82 - 5
Denture stomatitis in the elderly; Cumming CG et al.; A study was carried out of 121 elderly edentulous individuals living in institutionalised homes in the Lothian Region, Scotland to determine the prevalence of yeasts and associated oral disease . Clinical examinations found that 65(54%) of the individuals suffered from denture stomatitis, and yeasts were recovered from 51(78%) of these individuals . The main yeasts isolated were Torulopsis glabrata and Candida albicans . Culture of saliva samples produced a slightly higher recovery rate of yeasts compared with swabbing of the floor of mouth and palate . The number of cigarettes smoked per day had a significant positive effect on the presence of denture stomatitis . No difference in disease state was shown between secretors and non-secretors of blood group antigens in saliva . This study demonstrates a significant level of oral mucosal infection in an institutionalised elderly population.

Infect Immun, 1990 Apr, 58(4), 949 - 54
Genomic structure of Candida stellatoidea: extra chromosomes and gene duplication; Rikkerink EH et al.; Candida albicans and Candida stellatoidea are two closely related imperfect yeasts . Some isolates characterized as C . stellatoidea are in fact C . albicans, while others differ with respect to virulence and to karyotype, containing extra small chromosomes . Experiments in this study allowed us to infer that a typical C . stellatoidea isolate, Y2360, has 12 chromosomes rather than the 7 previously shown for C . albicans . The majority of cloned sequences tested hybridized to analogous chromosomes in C . albicans and in C . stellatoidea, although there were exceptions, and a repeated element isolated as specific for C . albicans hybridized to most of the chromosomes of C . stellatoidea . Several genes tested hybridized to one of the smaller, C . stellatoidea-specific chromosomes as well as to a larger one . The arrangement of restriction enzyme sites around the gene was the same in both the large and small chromosomes . For ADE2 and LYS2, the arrangements were identical to those of a typical C . albicans strain, FC18, suggesting a high degree of sequence conservation between the two species . Spheroplast fusion and segregation experiments showed that the ADE2 genes on both the large and small chromosomes of C . stellatoidea are active, implying that the organism is functionally at least triploid for this gene and probably for any others duplicated on the smaller chromosomes.

Bacteriol Virusol Parazitol Epidemiol, 1990 Apr-Jun, 35(2), 143 - 51
{A nutrient medium for culturing fungi based on a flores chamomillae infusion . II . The evaluation of the biological properties of fungi cultured on a medium with a flores chamomillae infusion}; Florescu I et al.; The paper reports on the biological properties of Candida albicans (strain I.C . - 130) cultivated on a medium with infusion of Flores chamomillae (I.F.C.) in parallel to the same strain cultivated on the medium Sabouraud (control) . The results obtained showed an identical phenotypical profile for the biological properties investigated (fermentation capacity of glucides, reduction of TTC, formation of chlamydospores on the PCB special medium, antigenic structure, sensibility to antifungal substances, virulence) . The qualities of the I.F.C . medium for the optimum insurance of the metabolic requirements of the fungi, for their recovery from clinical samples with a high rate of positivity, for ensuring the maintenance of the main biological properties of the fungi, to which the economical advantages are added (low price, easy availability of the raw material simple and rapid preparation methodology) recommend its use in the clinical laboratory, instead of the classical Sabouraud medium to which it corresponds qualitatively.

Biochem Biophys Res Commun, 1990 Mar 30, 167(3), 1177 - 83
A guanine nucleotide-sensitive, glucagon-stimulated adenylyl cyclase in Candida albicans: effect of glucagon on cell morphology; Paveto C et al.; GTP, GTP-gamma-S and Gpp(NH)p produced a significant activation of Mg2(+)-dependent adenylyl cyclase in permeabilized cells of Candida albicans . This activation was inhibited by GDP-beta-S . Maximal stimulation (4-6 fold) was obtained when Mg2+ and GTP-gamma-S were added during permeabilization . The guanine nucleotide-stimulated activity could be further activated by glucagon in a dose dependent manner being the maximal stimulation (4-5 fold) attained at 10(-6) M glucagon . Addition of the hormone to yeast cells incubated under conditions conducive to produce germ tubes blocked hyphal development and promoted multibudded cell morphology.

FEMS Microbiol Lett, 1990 Mar 15, 56(3), 249 - 54
Adherence of Candida albicans to components of the subendothelial extracellular matrix; Klotz SA; Candida albicans yeasts adhered avidly to extracellular matrix (ECM) proteins, type IV collagen, laminin, and fibronectin immobilized on plastic . Type IV collagen showed an increase of adherence of 400% above control values; laminin, 300%; and fibronectin, 150% . In addition, all three (in quantities of 0.02-200 micrograms/well of a culture tray) bound yeasts in a dose-response fashion . Adherence was inhibited when the proteins were preincubated with specific antibody, except with type IV collagen . Soluble laminin or fibronectin inhibited yeast adherence to the same proteins by 36 and 94%, respectively . Soluble fibronectin bound to the yeast surface and in so doing inhibited subsequent yeast adherence to fibronectin by 66% . By comparison, Candida albicans yeasts adhered in smaller numbers to glycosaminoglycans (GAGs) . Keratan sulfate, hyaluronic acid, chondroitin sulfate, Type B, and heparin actually decreased yeast adherence compared to control from 10% to 25%.

Gene, 1990 Mar 15, 87(2), 177 - 83
Cloning and characterization of the 2,3-oxidosqualene cyclase-coding gene of Candida albicans; Kelly R et al.; 2,3-Oxidosqualene (OS) cyclase (OSC) catalyzes the conversion of OS to lanosterol, an essential step in the biosynthesis of sterols . The Candida albicans gene (ERG7) encoding OSC was cloned by complementation of a Saccharomyces cerevisiae OSC mutant (erg7) . Two different Erg+ clones were isolated that contain a common overlapping region . The minimum region required for complementation was determined to be approx . 3.2 kb and a single 2.7-kb ERG7 transcript was detected . The cloned Candida ERG7 DNA complemented an additional nonconditional erg7 allele and a temperature-sensitive erg7 mutation . OSC activity was restored in the mutants as determined by {14C}acetate incorporation in vivo as well as incorporation in vitro in cell-free extracts using either {14C}isopentenyl pyrophosphate or {3H}OS as substrate . The level of OSC produced from expression of a single copy of the Candida ERG7 sequence was sufficient to allow growth of the S . cerevisiae erg7 mutants in the absence of exogenous ergosterol . These data support the contention that the Candida ERG7 sequence is the structural gene for OSC.

J Immunol, 1990 Mar 15, 144(6), 2205 - 10
Functional activation of human neutrophils by recombinant monocyte-derived neutrophil chemotactic factor/IL-8; Djeu JY et al.; Monocyte-derived neutrophil chemotactic factor (MDNCF)/IL-8, a novel cytokine, distinct from IL-1 and TNF was recently purified and cloned . This study was performed to investigate the biologic effect of recombinant MDNCF/IL-8 on human polymorphonuclear neutrophils (PMN) by assessment of their growth inhibitory activity against Candida albicans . The chemoattractant, FMLP was used as a positive control . We demonstrated that MDNCF/IL-8, similar to FMLP, effectively enhanced PMN-mediated anti-Candida activity . MDNCF/IL-8, from 1.0 to 1000 ng/mol, enhanced PMN-mediated anti-Candida activity, whereas FMLP was effective from 10(-10) to 10(-7) M . The optimal dose of MDNCF/IL-8 for PMN stimulation was 10 ng/ml which equalled the optimal chemoattractant dose . MDNCF/IL-8 itself, like FMLP, had no direct effect on Candida growth at any concentration and it stimulated antifungal activity only in PMN but not in monocytes . Interestingly, MDNCF/IL-8 failed to stimulate directly the production of superoxide from PMN or prime the respiratory burst of PMN exposed to FMLP . However, MDNCF/IL-8 was capable of releasing azurophilic enzymes from cytochalasin B-treated PMN into the extracellular space . Enhancement of PMN anti-Candida activity and release of azurophilic enzymes from PMN by MDNCF/IL-8 were inhibited in the presence of colchicine, which is a known inhibitor of degranulation . These results suggest that MDNCF/IL-8 induced antifungal action of PMN via oxygen-independent pathways . Furthermore, MDNCF/IL-8 induction of anti-Candida action by PMN was inhibited by pretreatment with Bordetella pertussis toxin, suggesting that enhancement of PMN antifungal activity by MDNCF/IL-8, as well as by FMLP, may be mediated by a GTP-binding protein.

J Biol Chem, 1990 Mar 5, 265(7), 3898 - 905
Salivary histatin 5: dependence of sequence, chain length, and helical conformation for candidacidal activity; Raj PA et al.; Histatin 5 (Asp1-Ser-His-Ala4-Lys-Arg-His-His8-Gly-Tyr-Lys-Arg12-Lys-Ph e-His-Glu16-Lys-His - His-Ser20-His-Arg-Gly-Tyr24), one of the basic histidine-rich peptides present in human parotid saliva and several of its fragments, 1-16 (N16), 9-24 (C16), 11-24 (C14), 13-24 (C12), 15-24 (C10), and 7-16 (M10), were synthesized by solid-phase procedures . Native histatin 5 from human parotid saliva was also purified . Their antifungal activities on two strains of Candida albicans have been studied and their conformational preferences both in aqueous and non-aqueous solutions examined by circular dichroism . The synthetic histatin 5, C16, and C14 peptides were highly active and inhibited the growth of C . albicans . The candidacidal activity data of synthetic histatin 5 were comparable to the values of the native histatin 5 isolated from parotid saliva and those reported previously, although the assay system used and the strains examined were different . The C16 fragment was as active as the whole peptide itself, whereas the N16 fragment was far less active than C14, suggesting that the sequence at the C-terminal is important for its fungicidal activity . An increase in the chain length of the C-terminal sequence from 12 to 16 residues increased the candidacidal activity, thereby indicating that a peptide chain length of at least 12 residues is necessary to elicit optimum biological activity . The CD spectra of these linear peptides showed that they are structurally more flexible, and they adopt different conformations depending on the solvent environment . CD studies provided evidence that histatin 5 and the longer fragments, C16, N16, and C14 preferred alpha-helical conformations in non-aqueous solvents such as trifluoroethanol and methanol, while in water and pH 7.4 phosphate buffers, they favored random coil structures . The shorter sequences seemed to adopt either turn structures or unordered structures both in aqueous and non-aqueous solutions . It appears that the sequence at the C-terminal of histatin 5 with a minimum chain length of 14 residues and alpha-helical conformation are the important structural requirements for appreciable candidacidal activity.

J Bacteriol, 1990 Mar, 172(3), 1276 - 83
Chromosomal rearrangements associated with morphological mutants provide a means for genetic variation of Candida albicans; Rustchenko-Bulgac EP et al.; At frequencies as high as 1.4%, the pathogenic yeast Candida albicans spontaneously gave rise to morphological mutants exhibiting more than 20 different types of abnormal colonies; approximately two-thirds of the mutants were stable, while the other one-third were unstable and produced mixtures of different colonial forms at very high rates . Abnormal electrophoretic karyotypes were observed for all of the 14 mutants that were examined, indicating that they were associated with different types of single and multiple gross chromosomal rearrangements . Because C . albicans is asexual and does not go through a meiotic cycle, we suggest that the high frequency of chromosomal rearrangements provides a means for genetic variation in this organism.

Diabetes, 1990 Mar, 39(3), 271 - 5
Handicaps to host defense . Effects of hyperglycemia on C3 and Candida albicans; Hostetter MK; The hyperglycemic patient remains persistently at risk for infectious complications . Whether ascribable to diabetes mellitus, to the administration of glucocorticoids, or to the infusion of hyperalimentation fluids, hyperglycemia may impair several mechanisms of humoral host defense, including such varied neutrophil functions as adhesion, chemotaxis, and phagocytosis . In addition, binding of glucose to the biochemically active site of the third component of complement C3 inhibits the attachment of this protein to the microbial surface and thereby impairs opsonization . Last, several pathogens frequently encountered in hyperglycemic patients possess unique mechanisms of virulence that flourish in the hyperglycemic environment . Most notable in this regard is the yeast Candida albicans, which expresses a glucose-inducible protein that is structurally and functionally homologous to a complement receptor on mammalian phagocytes . This protein promotes adhesion in the yeast and subverts phagocytosis by the host . Thus, hyperglycemia serves as a central mechanism in the predisposition of hyperglycemic patients to infection.

Clin Immunol Immunopathol, 1990 Mar, 54(3), 347 - 53
Identification of immunodominant antigens of Candida albicans in patients with superficial candidosis; Weller BI et al.; The aims of this study were to identify the immunodominant protein antigens of Candida albicans in patients with superficial infections of the oral and vaginal mucosa . Cytoplasmic protein extract from C . albicans was analyzed by the immunoblot technique using sera from 20 patients with chronic atrophic oral candidosis, from 8 patients with vulvovaginal candidosis, and from 20 control subjects . A significantly greater proportion of patient sera reacted with the 65- and 32-kDa antigens when compared with sera from controls (P less than 0.001) . Sera from patients also reacted more often with 38- and 29-kDa antigens (P less than 0.05), while sera from both patients and controls reacted with the 47-kDa antigen . The identified 65-, 38-, 32-, and 29-kDa antigens may be of importance for the development and also for the recurrence of superficial candidosis of the oral and/or vaginal mucosa.

Mikrobiol Zh, 1990 Mar-Apr, 52(2), 53 - 6
{The antilysozyme activity of yeasts in the genus Candida}; Sheremet ZA et al.; The fungi of the genus Candida isolated from patients with oral mucosa candidiasis and from candidiasis carriers have been studied for their antilysozyme activity . These fungi (Candida albicans, C . tropicalis, C . krusei, C . quilliermondii) are antilysozyme-active . A high antilysozyme activity of the fungi isolated from patients with oral mucosa candidiasis permits supposing that the presence of this trait may be one of the factors of microorganism pathogenicity . The effective antimycotic therapy (clotrimasole, sanguirhitrin) decreases the antilysozyme activity of fungi of the genus Candida.

Rinsho Ketsueki, 1990 Mar, 31(3), 330 - 4
{Multiple liver abscesses due to Candida albicans in a patient with acute promyelocytic leukemia: percutaneous transhepatic intraportal administration of amphotericin B}; Ishii H et al.; A 36-year-old male with acute promyelocytic leukemia in second relapse was admitted to receive reinduction therapy in June, 1985, and entered into third complete remission, but he developed spiky fever after chemotherapy . Ultrasonic tomography revealed multiple liver abscesses and culture of the aspirates demonstrated Candida albicans in the abscesses . He was treated with intravenous administration of amphotericin B (AMPH-B) but the effect on the liver abscesses was unsatisfactory and consolidation therapy was difficult to start . AMPH-B (30 mg/day) was administered by percutaneous transhepatic intraportal administration (PTIA) . About two months later, multiple liver abscesses disappeared . No remarkable complications such as severe fever, chill and renal dysfunction were recognized during PTIA of AMPH-B . So PTIA of AMPH-B is considered to be useful and safe for the management of fungal liver abscesses.

S Afr J Surg, 1990 Mar, 28(1), 26 - 7
Pancreatic candidiasis . A case report; Mannell A et al.; A rare case of pancreatic candidiasis is described . The patient presented with weight loss, obstructive jaundice and a mass in the head of the pancreas . Intra-operative fine-needle aspiration cytology was consistent with a well-differentiated adenocarcinoma of the pancreas and a radical pancreaticoduodenectomy was performed . However, histological examination of the resected specimen revealed acute-on-chronic pancreatitis complicated by candidiasis with no evidence of malignant disease . The association between this variety of pancreatic candidiasis and pancreatic abscesses due to Candida albicans in acute pancreatitis is discussed.

J Antimicrob Chemother, 1990 Mar, 25(3), 361 - 6
In-vitro evaluation of the antifungal activity of amphotericin B entrapped into liposomes during storage for one year; Heymans C et al.; The stability of the antifungal activity of amphotericin B entrapped in small sonicated liposomes (ampholiposomes) was studied in vitro over a one-year period . Preparations of ampholiposomes stored at -20 degrees C or at 4 degrees C were compared monthly with freshly-prepared ampholiposomes and a commercial preparation of amphotericin B-deoxycholate (Fungizone; Squibb) by a killing curve method with Candida albicans . The bioactivity of the four preparations, each containing 1.5 or 2 mg/l of amphotericin B, was measured as the initial rate of killing and the 'relative bioactivity' . Relative bioactivity was calculated as the percentage reduction of the area under the growth curve compared with control growth . Storage of ampholiposomes for one year did not decrease their antifungal activity . Storage of ampholiposomes containing 1.5 mg/l amphotericin B for one year at -20 degrees C, but not at 4 degrees C, gave a significant increase in relative bioactivity and killing rate in comparison with freshly-prepared ampholiposomes . This was probably due to modifications in the spatial configuration of phospholipids and amphotericin B . The persisting antifungal activity of ampholiposomes stored for one year should allow the preparation of large batches to perform comparative clinical studies.

J Obstet Gynecol Neonatal Nurs, 1990 Mar-Apr, 19(2), 171 - 3
Candidiasis in the breastfeeding mother and infant; Johnstone HA et al.; Candidiasis in a breastfeeding mother and infant is described . The mother's breasts were a continuous source of Candida albicans, resulting in persistent thrush in the infant . The infant and mother were successfully treated with clotrimazole in a gel form . This report emphasizes the importance of treating both the infected mother and infant to prevent reinfection and ensure successful breastfeeding.

Przegl Dermatol, 1990 Mar-Apr, 77(2), 118 - 21
{Incidence and enzymatic properties of yeast-like fungi . Examination of workers of various departments of the District Meat-Processing Industry in Białystok}; Niczyporuk W et al.; In a group of 111 workers of the District Meat Processing Plant clinical examination of the skin and cultures for Candida organisms were performed . The proteolytic and lipolytic properties of these fungi were analysed . From the interdigital spaces of hands 42 strains were isolated, with the species Candida albicans accounting for 13.5% of the strains (15) . Case history and the character of skin lesions on the hands and forearms suggested that they were caused by skin contact with meat and internal organs producing the so called "gut eczema" while Candida was secondary agent causing exacerbation of skin changes.

Przegl Dermatol, 1990 Mar-Apr, 77(2), 107 - 10
{Fungal flora in mycoses among the population of the south-eastern Poland 1978-1988}; Ratka P et al.; In the years 1978-1988 a group of 2257 subjects was examined for the presence of fungal infection . In 785 cases positive results of cultures were obtained yielding 468 dermatophytes (60.1%) and 317 yeast-like fungi (39.9%) . The most frequently isolated fungi were: Candida albicans (27.3%), Trichophyton mentagrophytes v . interdigitale (27.0%) and Trichophyton rubrum (20.6%) . In the subgroup of dermatophytes anthropophilic fungi accounted for 87.5%.

Farmaco, 1990 Mar, 45(3), 303 - 12
New heterocyclic derivatives of benzimidazole with germicidal activity--VII--2-(5'-nitro-2'-furyl or 2'-thienyl) benzimidazoles with different substituents in the 5-position; Pedini M et al.; In continuation of our previous research, the synthesis of 13 2-(5'-nitro-2'-furyl or 2'-thienyl) benzimidazoles with different substituents in 5 position is described . The new compounds were tested in vitro against 5 (Gram+) and 4 (Gram-) strains and a mycete Candida Albicans . All the derivatives showed a certain degree of antibacterial and antimycotic activity, which in some cases was fairly good.

Hua Xi Yi Ke Da Xue Xue Bao, 1990 Mar, 21(1), 59 - 62
{Purification and identification of antimicrobial peptides of rabbit neutrophils}; Wu Q et al.; Five antimicrobial peptides were extracted from the cytoplasmic granules of rabbit neutrophils with 0.01 mol/L citric acid . SDS-PAGE gel densitometric analysis of the citric acid extract showed that they accounted for 34%-42% of the total extract proteins . When subjected to acid urea polyacrylamide gel electrophoresis, five peptides migrated much further to the cathode than lysozyme . Beginning with the most cathodal component, they were in turn referred to as NP1, NP2, NP3, NP4, and NP5 . They were purified from the citric acid extract by virtue of preparative polyacrylamide gel electrophoresis . Each of them was of low molecular weight (2,500-6,000) as determined by SDS-PAGE . Three of the peptides were tested in vitro for fungicidal activity . When Candida albicans (10(7)/ml) were incubated with 12.5 micrograms/ml of NP1 or NP2 at 37 degrees C for 2 h, the death rates of the organisms were 96.6% and 93.3% respectively . NP3 was shown to be active against Candida albicans although less potent than NP1 and NP2.

J Oral Pathol Med, 1990 Mar, 19(3), 136 - 41
Experimental oral candidosis in the mouse: microbiologic and histologic aspects; Lacasse M et al.; A model of oral candidosis was developed in order to investigate histologic and microbiologic aspects of this host-parasite interaction under controlled experimental conditions . Normal adult CD-1 mice were inoculated by the topical application of 10(8) Candida albicans blastospores, and oral colonization was monitored by the quantitative culturing of saliva samples and of digested oral mucosa . Tissue sections of the mucosa were examined in a kinetic study ranging from 2 h to 13 days postinoculation . We report here that oral colonization by C . albicans can be induced in normal adult mice without the use of any compromising agent and that the animals recover from this mucosal infection following a reproducible pattern . Temporal analysis of the oral histopathology showed that distinct patterns of inflammation are associated with particular stages in the development of the infectious foci . This experimental model offers a means of further investigating the host-parasite interactions involved in the onset and development of oral candidosis.

Rev Infect Dis, 1990 Mar-Apr, 12 Suppl 3, S294 - 8
Efficacy of fluconazole in prophylaxis and treatment of experimental Candida endocarditis; Longman LP et al.; The efficacy of fluconazole, a bis-triazole antifungal agent, for prophylaxis and treatment of endocarditis due to Candida albicans and Candida parapsilosis is assessed in a rabbit model . Fourteen daily injections of fluconazole at doses of 20 and 10 mg/kg of body weight eradicated C . albicans and C . parapsilosis, respectively, from the cardiac vegetations in all animals tested . Amphotericin B (3 mg/kg) and flucytosine (35 mg/kg) both singly and in combination failed to achieve eradication in 100% of the animals . A two-dose prophylactic regimen of 30 mg of fluconazole/kg was consistently successful in preventing experimental endocarditis caused by C . albicans or C . parapsilosis.

Rev Infect Dis, 1990 Mar-Apr, 12 Suppl 3, S272 - 5
Susceptibility of Candida albicans and other yeasts to fluconazole: relation between in vitro and in vivo studies; Galgiani JN; In vitro studies of fluconazole have demonstrated that test results can be influenced by several test conditions, including medium composition, pH, and size of the starting fungal inoculum . In studies with Candida albicans, a few isolates have been identified that are markedly more resistant than other strains of the same species; in several in vivo studies of experimental infections, the more resistant isolates have caused infections less susceptible to fluconazole treatment . These findings corroborate a relation between in vitro and in vivo results . With further work it should be possible to define standard methods for use by clinical laboratories in determining fungal susceptibility to fluconazole.

J Clin Microbiol, 1990 Mar, 28(3), 614 - 5
Rapid, colorimetric identification of Candida albicans; Perry JL et al.; A total of 706 yeast isolates were evaluated in parallel by the Candida albicans Screen (CAS; Carr-Scarborough Microbiologicals, Inc., Stone Mountain, Ga.) test and the germ tube (GT) test in comparison with the API 20C Yeast Identification System . The CAS and GT tests correctly identified 419 of the 422 isolates of C . albicans (99.3%) . Two of the false-negative reactions occurring with the CAS were with GT-negative strains of C . albicans . There were two false-positive CAS reactions involving a single strain each of C . parapsilosis and C . tropicalis . Sensitivity and specificity for both tests exceeded 99%, with positive and negative predictive values of 99 and 98%, respectively.

Biochem J, 1990 Mar 1, 266(2), 475 - 80
Interaction of azole antifungal antibiotics with cytochrome P-450-dependent 14 alpha-sterol demethylase purified from Candida albicans; Hitchcock CA et al.; The interaction of azole antifungal antibiotics with purified Candida albicans cytochrome P-450-dependent 14 alpha-sterol demethylase (P-450DM) was measured spectrophotometrically and by inhibition of enzyme activity . Ketoconazole and ICI 153066 (a triazole derivative) formed low-spin complexes with the ferric cytochrome and induced type II difference spectra . These spectra are indicative of an interaction between the azole moiety and the sixth co-ordination position of P-450DM haem . Both azoles inhibited the binding of CO to the sodium dithionite-reduced ferrous cytochrome, and inhibited reconstituted P-450DM activity by binding to the cytochrome with a one-to-one stoichiometry . Similarly, total inhibition of enzyme activity occurred when equimolar amounts of clotrimazole, miconazole or fluconazole were added to reconstituted P-450DM . These results correlated with the inhibition of P-450DM in broken cell preparations, confirming that all five azoles are potent inhibitors of ergosterol biosynthesis in C . albicans.

Immunology, 1990 Mar, 69(3), 335 - 41
Allergen presentation by epidermal Langerhans' cells from patients with atopic dermatitis is mediated by IgE; Mudde GC et al.; To investigate the role of IgE-bearing Langerhans' cells (LC) from atopic dermatitis (AD) patients in antigen presentation, IgE+LC and non-IgE bearing LC (IgE-LC) from AD patients were investigated for their antigen-presenting capacity and compared to antigen-presenting cells (APC) from peripheral blood . The T-cell response to Candida albicans, using IgE+LC from AD patients as APC, was in the same range as with IgE-LC . Also, the T-cell response to Candida with autologous APC from peripheral blood did not significantly differ between these groups . In contrast to this finding, the T-cell response to house dust allergen (HDA) was dependent on the type of APC used . If non-T cells from peripheral blood were used as APC, both AD patients and controls responded to HDA . However, when LC were used as APC, a T-cell response to HDA was only observed in the presence of IgE+LC . IgE-LC from AD patients or LC from normal controls were unable to present HDA . Preincubation of IgE+LC with anti-IgE or anti-kappa/lambda antibodies inhibited HDA-induced T-cell proliferation, whereas the response to Candida was not affected . These in vitro results, which demonstrate the necessity of cell-bound IgE on LC for the presentation of aero-allergens, strongly correlate with the in vivo presence of a positive delayed patch reaction to the same antigens . When the LC of a patient appeared to be IgE-, the in vitro proliferative response as well as, in most cases, the in vivo patch test reaction to the same antigens was negative . In conclusion, these experiments demonstrate that there are at least two different mechanisms by which LC capture antigens for antigen presentation . In one of them cell-bound IgE, as can be demonstrated on LC from AD patients, plays a crucial role . The binding and presentation of HDA by APC from peripheral blood can take place independently of cell-bound IgE . Candida can be presented by both types of APC in the absence of IgE.

Mycoses, 1990 Mar, 33(3), 129 - 35
Bioassay for determination of nystatin in faeces after oral application; Blaschke-Hellmessen R et al.; An optimized bioassay (agar diffusion assay) using a defined Candida albicans strain as tester strain for determination of nystatin excreted with the faeces during and after oral application is presented . The sensitivity of the test achieves 39 IU nystatin/g faeces relating to the total amount of nystatin (using dimethylformide for solution of nystatin in the faeces) and 78 IU nystatin/g faeces relating to the biologically active portion (using aqua dest for suspension of nystatin from the faeces) . Precision and reproducibility of the bioassay are assured by standardized procedures . By means of the bioassay, doses and application intervals for orally administered nystatin can be optimized.

J Clin Immunol, 1990 Mar, 10(2), 90 - 8
Depressed T-cell reactivity to recall antigens in rheumatoid arthritis; Verwilghen J et al.; Reactivity toward soluble recall antigens (Candida albicans, cytomegalovirus, herpes simplex, streptokinase-streptodornase, and influenza) was determined in cultures of peripheral blood mononuclear cells from 41 rheumatoid arthritis patients (with clinically active as well as inactive disease) and from 28 controls . In the group with clinically active rheumatoid arthritis we found an increased incidence of "anergy," defined as nonreactivity to three or more antigens . In an attempt to explain this decreased antigen reactivity, the latter was correlated with peripheral blood lymphocyte subsets, as defined by two-color immunofluorescence with a panel of eight monoclonal antibodies . We found a significantly lower number of memory T4 cells (CD4+CD45RA-) and a significantly higher number of the CD3-CD57+ (nonspecific suppressor) cells and of CD3-CD56+/CD16+ (natural killer) cells in anergic RA patients . In the total group of rheumatoid arthritis patients, the antigen reactivity correlated positively with the percentage of memory T4 cells . Antigen reactivity was negatively correlated with the percentage of CD3-CD57+ cells and of the CD3- natural killer cells in peripheral blood . Our data suggest that a decrease in memory T4 cells and an increase in nonspecific suppressor cells may contribute to the impaired cellular immune function in peripheral blood of rheumatoid arthritis patients.

Rev Infect Dis, 1990 Mar-Apr, 12(2), 258 - 66
Application of DNA typing methods to Candida albicans epidemiology and correlations with phenotype; Stevens DA et al.; The application of methods of Candida albicans DNA fragment length polymorphism analysis to correlations with phenotype and to questions in the epidemiology of Candida is shown . Twenty-nine different DNA types, in two broad classes, have thus far been demonstrated in 91 isolates . One type, IA2, was easily the most common (41% of isolates) . A type is constant after multiple generations in vivo, as demonstrated in a mouse model . Isolates from individual medical centers were polymorphic, and DNA types were widely distributed geographically . Persons colonized with and/or having disease due to C . albicans at two or more body sites almost always had the same individual type . Sex partners studied had the same type in genital isolates . There was neither tight concordance nor random association of DNA type with previously described phenotypic groups . Likewise, some phenotypic characteristics were significantly associated with DNA type . Urogenital isolates were significantly associated with DNA type IA2 . Colonizing and invading isolates included many different and overlapping DNA types . A cluster of cases in a hospital, previously reported to have been caused by a single organism (based on phenotypic studies), was shown to be due to multiple types . Phenotype switching, associated with transition from colonization to invasion, is suggested in these studies . The present series of studies demonstrates the application of DNA typing methods to classification and clinical problems.

Infect Immun, 1990 Mar, 58(3), 625 - 31
A monoclonal antibody that defines a surface antigen on Candida albicans hyphae cross-reacts with yeast cell protoplasts; Ollert MW et al.; Female BALB/c mice were immunized with a whole-hyphal-cell extract obtained from Candida albicans wild-type strain 4918 grown in Lee medium . Monoclonal antibody (MAb)-producing hybridomas were prepared by fusing immune splenocytes with NS-1 myeloma cells . One of the hybrid cell clones (1.183) secreted an immunoglobulin G1 antibody that reacted with C . albicans hyphae in an indirect immunofluorescence assay but not with yeast cells and pseudohyphal segments directly originating from parent blastoconidia . In the same assay eight of nine recent clinical C . albicans isolates and Candida stellatoidea tested positive for hyphal cell-specific reactivity with MAb 1.183 . The recognized antigen on hyphal cells was sensitive to heat treatment, beta-mercaptoethanol reduction, and proteolysis with pronase, trypsin, and subtilisin . Western blot (immunoblot) analysis of hyphal whole-cell and dithiothreitol extracts with MAb 1.183 revealed two major proteins with approximate molecular masses of 55 and 60 kilodaltons (kDa) under reducing conditions . Endo-alpha-N-acetylgalactosaminidase (O-glycanase) treatment reduced the molecular mass of the 60-kDa protein slightly but did not affect recognition by MAb 1.183, whereas peptide:N-glycosidase F (N-glycanase) had no effect on either protein . When exponentially growing yeast cells were treated sequentially with EDTA, beta-mercaptoethanol, and Zymolase to form protoplasts, a specific immunofluorescence signal was obtained with MAb 1.183 . In a Western blot, MAb 1.183 showed reactivity with a 20-kDa protein in the sodium dodecyl sulfate extract from protoplasts, whereas no reactivity was found with cell wall material obtained from yeast cells . In summary, these experiments indicated that specific cell surface components from C . albicans hyphae are related to antigens which are present in yeast cells but are not detectable on the surface of the latter.

Arch Biochem Biophys, 1990 Feb 15, 277(1), 122 - 9
Characteristics of L-alanine:4,5-dioxovaleric acid transaminase: an alternate pathway of heme biosynthesis in yeast; Hoare K et al.; The present study reports for the first time the presence of the enzyme L-alanine:4,5-dioxovaleric acid transaminase (EC 2.6.1.43), which catalyzes the irreversible synthesis of 5-aminolevulinic acid in three strains of yeast: Candida albicans 3100, Saccharomyces cerevisiae 3059, and S . cerevisiae S288C . The enzyme was predominantly present in the cytosol and was purified from C . albicans 3100 by about 200-fold with an overall yield of 23% to apparent homogeneity . The purification procedure involved heat treatment, followed by affinity chromatography on L-alanine-Sepharose CL-4B, ion-exchange chromatography on DEAE-cellulose DE-52, and chromatography on hydroxyapatite . As judged by gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the enzyme appeared to be a monomeric protein of relative molecular mass 59,000 . The enzyme activity was stimulated by pyridoxal phosphate and was optimally active at 60 degrees C . The purified enzyme had an isoelectric point of 4.7 and a pH optimum of 7.2 Km values of the enzyme for L-alanine, pyridoxal phosphate, and 4,5-dioxovaleric acid were 2.8 X 10(-7), 5.0 X 10(-7), and 1.05 X 10(-5) M, respectively . The Vmax of the enzymatic reaction was 5 X 10(-6) mol/mg/h . Antibody raised against the purified yeast L-alanine:4,5-dioxovaleric acid transaminase did not cross-react with the same enzyme from rat liver and kidney.

Infect Immun, 1990 Feb, 58(2), 378 - 83
Caveats in the investigation of form-specific molecules of Candida albicans; Brawner DL et al.; Numerous reports purporting the existence of form-specific antigens of Candida albicans have been published, but it is generally unclear whether antigenic variability is an acceptable alternative interpretation . In this study, we used indirect immunofluorescence and immunogold electron microscopy to determine the distribution and form specificities of two antigens during yeast and hyphal growth in several defined and complex media . The results confirmed that antigen expression varies with length of incubation, nutrition, and serotype and indicate that the form specificities of antigens may be misinterpreted when conclusions are based exclusively on indirect immunofluorescence and extraction procedures . We therefore suggest that investigations be designed to include serotype A and B isolates grown in both complex and chemically defined media and that agglutination, immunofluorescence, or enzyme-linked immunosorbent assays on whole cells or cell extracts be used as presumptive tests . Confirmation of form-specific antigens should be done by appropriate immunoelectron microscopic evaluation.

Cesk Oftalmol, 1990 Feb, 46(1), 42 - 6
{Nystatin in the treatment of candidal conjunctivitis}; Haicl P; The author presents the case-history of a 19-year-old female patient with subacute bilateral conjunctivitis, where based on repeated cultivation form the conjunctival sac Candida albicans was proved as the aetiological agent . After the application of Nystatin (Fungicidin Spofa ointment, dragee) marked immediate improvement of the clinical finding was recorded and gradual regression of follicles and tarsal squamous hyperplasia . The author discusses possible types of mycotic conjunctivitis with regard to the character of the inflammation, the aetiological agent and treatment.

J Med Chem, 1990 Feb, 33(2), 877 - 80
Design and synthesis of 14 alpha-methyl-15-aza-D-homosterols as novel antimycotics; Dolle RE et al.; A novel series of 14 alpha-methyl-15-aza-D-homosterols 3-7 has been synthesized . These compounds display significant antimycotic activity in vitro (MIC = 0.8-3.1 micrograms/mL) that compares quite favorably to the activity observed for fluconazole (MIC = 0.8 micrograms/mL) . Azasterols 3 and 4 were active in vivo as reflected in the increased survival time of Candida albicans infected mice . The antimycotic activity of 3-7 is hypothesized to be a consequence of the inhibition of fungal 14,15-sterol reductase.

Av Odontoestomatol, 1990 Feb, 6(2), 151 - 4
{Denture stomatitis . Its relation to candida albicans}; Ceballos A et al.; One of the most usual complications of the patients that carry a prosthesis is one called stomatitis denture . Its etiology is not clear enough . In this work we study ninety people, sixty of them wear prosthesis . We take samples of different places in the mouth to plate and class C . Albicans . We look for the relationship of results with the clinical parameters of the patient.

Photodermatol Photoimmunol Photomed, 1990 Feb, 7(1), 25 - 7
Is nifedipine phototoxic?
Guarrera M, Parodi A, Rebora A.
Circumstantial evidence of phototoxicity of nifedipine is poor, being based only on uncontrolled clinical evidence . The authors have assessed nifedipine phototoxicity in vitro by photohemolysis and Candida albicans tests and found it measurable at 10 and 100 micrograms/ml . These dosages exceed the 0.1 microgram/ml blood levels that are usually attained in vivo.

Mycoses, 1990 Feb, 33(2), 90 - 4
Fungal flora of human faeces in psoriasis and atopic dermatitis; Buslau M et al.; Faeces samples taken from 343 patients with psoriasis and 581 patients with atopic dermatitis were subjected to mycological examination . Yeasts were detected in 68% of the psoriatics and in 70% of the patients with atopic dermatitis but in only 54% of the controls (n = 50) . Qualitative analysis revealed a predominance of Candida albicans . Non-pathogenic yeasts constituted only 1% in each of these groups . Of the hyphomycetes, Geotrichum candidum occurred in 22% of the psoriatics, in 10% of the atopic dermatitis patients and in 3% of the controls . Aspergillus species were found in 1% of the patients but not in the controls . Stool samples collected on three consecutive days from 141 patients were examined for yeasts . Qualitative correlation between all three samples was shown in 95% of the patients and quantitative correlation in 38% . Deviations were mainly of exponential magnitude . Germ cell concentration of 10(4) cells per ml and above were measured in 38% of the psoriatics and in 28% of the atopic dermatitis patients but in only 22% of the test subjects with healthy skin . There was no correlation between the concentration levels of yeasts in the faeces and the extent of psoriasis or atopic dermatitis.

J Chemother, 1990 Feb, 2(1), 55 - 61
The effect of antimycotics on secretory acid proteinase of Candida albicans; Angiolella L et al.; The effect of antimycotics on secretory aspartate (acid) proteinase, a virulence enzyme of Candida albicans, was investigated . The conditions of the study were such as to induce proteinase production in the stationary phase of growth (25-40 hours), when no antifungal tested, except the polyene derivative methyl partricin, significantly reduced the viability of the culture . Among azole derivatives, fenticonazole (FZ) but not miconazole, fluconazole or ketoconazole, exerted strong inhibition on proteinase, in typical dose-diphasic pattern, (0.01 microgram/ml; 1-10 micrograms/ml) . 5-fluorocytosine (5-FC) was also inhibitory at a dose interval 1-10 micrograms/ml . In all cases, the inhibition concerned the synthesis of the enzyme rather that its activity as suggested by the results of comparative ELISA, SDS-PAGE and spectrophotometric methods of proteinase detection . Finally, the inhibition of proteinase production by FZ and 5-FC mainly reflected the effect of these antimycotics on general protein synthesis.

J Antimicrob Chemother, 1990 Feb, 25(2), 237 - 45
Antimycotic effects of octenidine and pirtenidine; Ghannoum MA et al.; The effects of octenidine and pirtenidine on yeasts (in particular Candida albicans) have been studied . MIC and MCC values have been established as well as the inhibitory effects on growth, budding and germ tube formation . The drugs were shown to cause extensive leakage of cytoplasmic contents from the cells which was correlated with morphological and ultrastructural changes in the yeast.

Mycopathologia, 1990 Feb, 109(2), 99 - 109
Experimental pulmonary candidiasis; Sawyer RT; The initial interaction of Candida albicans with pulmonary tissue of B6D2/F1 mice was investigated . The LD50 for mice challenged intravenously (IV) was approximately 3 X 10(5) yeasts, whereas the LD50 by the intratracheal (IT) route was in excess of 10(8) yeasts . Mice challenged IV died of progressive yeast growth in the kidneys . In contrast, mice challenged IT rapidly eliminated the entire inoculum by the first day after challenge . Resident pulmonary alveolar macrophages (PAM) killed upwards of 70% of C . albicans in an in vitro killing assay . At effector: target ratios favoring the effector cell population resident PAM were able to restrict the formation of yeast germ tubes to only 30% of the yeasts, whereas at equivalent ratios virtually all of the intracellular yeasts produced germ tubes . Evaluation of the ability of PAM, harvested from genetically different strains of inbred mice, to kill C . albicans in vitro showed that killing ability was a property of resident PAM from mice with the black 6 background . It was discovered that during the initial stages of infection in vivo, the expression of the F4/80 surface molecule was down regulated, and the expression of the Mac 1 surface molecule upregulated . There were no quantitative changes in expression of either Mac 2, Mac 3, Ly 5 or the 5C6 surface epitopes . Taken together, the data show that pulmonary tissue is quantitatively very resistant to C . albicans infection, because of the ability of resident PAM to rapidly phagocytize and kill yeasts . Killing of C . albicans by resident PAM may be a property of a subset of this mononuclear phagocyte population and was accompanied by alterations in the expression of surface molecules.

Mycopathologia, 1990 Feb, 109(2), 123 - 37
Models for studying the role of fungal attachment in colonization and pathogenesis; Kennedy MJ; Fungal adhesion and aggregation is considered an important event in human, animal and plant disease as well as in the ecology of fungi in nature (e.g., in mating reactions and the dispersion of fungal propagules) . Because of this, numerous models have been developed to study fungal adhesion and aggregation mechanisms over the last decade . Unfortunately, however, nearly all of the work in this area has been carried out in simple in vitro models and has focused its attention on that of the attachment process alone, while realitively little effort has been made toward understanding the role adhesion and aggregation plays in colonization or pathogenesis . The emphasis on adhesion and aggregation mechanisms appears, therefore, to have somewhat obscured the study of the interaction of adhesion with other factors that may be of equal or greater importance in these processes and to the development of more complex adhesion models to explore the relationship between adhesion and colonization . Moreover, because it has not generally been appreciated that several methodologic pitfalls accompany the use of simple in vitro adhesion models, there is now emerging a confused literature base with regard to: (i) the nature of the cell wall component(s) of Candida albicans that mediates its attachment to, for example, epithelial cells; (ii) the mechanism(s) of invasion of mucosal and endothelial surfaces; and (iii) the role certain adhesive reactions observed in vitro play in colonization and pathogenesis by this fungus . Therefore, with an emphasis on C . albicans, this paper will attempt to put into perspective the uses and limitations of models for studying the role of fungal attachment in colonization and pathogenesis . In addition, factors that can modify fungal adhesion data will be discussed and the beginnings of a standardized assay to study the adhesion of C . albicans to buccal epithelial cells will be described.

J Gen Microbiol, 1990 Feb, 136 ( Pt 2), 311 - 7
Influence of applied electrical fields on yeast and hyphal growth of Candida albicans; Crombie T et al.; Yeast cells of Candida albicans which had been attached to polylysine-coated microscope slides were induced to form buds or germ tubes in the presence of external electrical fields . The sites of budding and germ tube formation and the growth of germ tubes and hyphal branches were polarized preferentially towards the cathode . Buds were not converted to pseudohyphae or germ tubes by the field and the field had no effect on the positioning of nuclei or septa in the yeast cell or germ tube . Buds were less polarized than germ tubes at any given applied voltage . The polarization of buds reached a peak at an electrical field of 12 mV per cell . Polarization of germ tubes was biphasic, increasing rapidly with increasing field strengths up to 5 mV per cell, and then more slowly in stronger fields . An electrical field was only required for a fraction of the time taken for germ tubes to start to form, so cells retained a memory of experiencing an electrical field which influenced the selection of sites of evagination . Increasing the electrical field delayed the time of germ tube evagination and inhibited the rate of germ tube extension . Unlike previous findings with other filamentous fungi, germ tubes grew unidirectionally towards the cathode for extended periods and did not deviate to a perpendicular orientation . This result suggests that the septal pore of the filamentous form may have high electrical resistance and would act as an effective barrier to solute transport between intercalary compartments.

Acta Odontol Scand, 1990 Feb, 48(1), 85 - 8
The role of yeasts in oral cancer by means of endogenous nitrosation; Krogh P; Oral leukoplakias, particularly non-homogeneous types, are often invaded by yeasts, with Candida albicans being the dominant species . The more advanced precancerous leukoplakia lesions yield more rarely occurring biotypes of C . albicans, suggesting a causal role for these biotypes in the malignant transformation . N-nitroso-benzylmethylamine (NBMA) is a compound able to induce carcinoma of the esophagus and the oral cavity in the rat . The catalytic potential of yeasts, isolated from leukoplakia lesions and from normal mucosa, to produce NBMA from the precursors N-benzyl-methylamine and nitrite was assessed at pH 6.8 . The yeast strains differed in nitrosation potential, ranking from 0 to 1.2 micrograms NBMA/10(6) cells . C . albicans strains of the more rarely occurring biotypes showed the highest nitrosation potential, whereas C . tropicalis, C . parapsilosis, and Torulopsis glabrata were ranked lower . Strains with high nitrosation potential were generally isolated from lesions with more advanced precancerous changes . Thus, further evidence is provided supporting the hypothesis that yeasts play a causal role in oral cancer by means of endogenous nitrosamine production.

Acta Odontol Scand, 1990 Feb, 48(1), 37 - 43
Histopathology, immunology, and serology of oral yeast infections . Diagnosis of oral candidosis; Budtz-Jorgensen E; For diagnostic purposes it is normally not important to obtain a biopsy specimen, since an oral smear from the lesion will yield blastospores and pseudohyphae in abundance . However, in lesions that respond poorly to antimycotic treatment a biopsy should be carried out to detect possible malignant changes in the epithelium . Assessment of cell-mediated immunity against Candida albicans and other antigens may be important in patients with severe chronic candidosis to assess the degree of immunocompetence and prognosis . Usually, patients with oral candidosis show only moderately elevated antibody titers in serum and saliva against C . albicans, and serologic tests are normally not a diagnostic tool for oral candidosis . However, such tests may be a prognostic instrument in patients with severe oral candidosis who respond poorly to antimycotic therapy.

Acta Odontol Scand, 1990 Feb, 48(1), 11 - 8
Clinical-mycologic diagnosis of oral yeast infections; Olsen I et al.; Conventional oral specimens for recovery of yeasts are swabs and smears . Oral rinses and imprint/impression cultures can also be used . Yeasts grow well at room temperature and may multiply in specimens under transport . Direct smears examined for blastospores, hyphae, and inflammatory cells ensure rapid presumptive diagnosis . Fungal identification requires culture, preferably on different media and at different temperatures to ensure recognition of all species present . YM agar supplemented with 0.01% aniline enables detection of Candida albicans and C . parapsilosis on primary plates through fluorescence . Microstix-Candida or Oricult-N slides can be read after culture at room temperature . Histologic sections for demonstration of yeasts require periodic acid-Schiff, Gridley, or Gomori's methenamine silver staining . Fungiqual staining enables non-specific diagnosis, also of rare oral mycoses, within 30 min, through fluorescence . Calcofluor white is even faster (less than 30 sec) . Specific antibodies labeled with fluorescent stain enable more precise mycologic diagnosis . Mycologic findings should be interpreted together with clinical findings.

Immunol Cell Biol, 1990 Feb, 68 ( Pt 1), 15 - 20
Murine candidiasis: cell-mediated immune responses correlate directly with susceptibility and resistance to infection; Ashman RB; Cell-mediated immune responses were evaluated after immunization in two inbred mouse strains, CBA/H and BALB/c, that are respectively susceptible and resistant to infection with the yeast Candida albicans . Local immune responses, as measured by leucocytic infiltration into the draining lymph node, were similar; however, both delayed-type hypersensitivity responses and candida-specific lymphocyte proliferation in vitro were significantly stronger in the resistant strain . The response was controlled by genes mapping outside the major histocompatibility complex . A possible explanation for the down regulation of the immune response in CBA/H mice is discussed.

Am J Obstet Gynecol, 1990 Feb, 162(2), 332 - 6
Recurrent allergic vulvovaginitis: treatment with Candida albicans allergen immunotherapy; Rigg D et al.; Recurrent vaginal candidiasis is a difficult problem for many women who do not respond to the usual antifungal agents . Normally these women have recurrent disease for many years before they are referred for evaluation of local vaginal hypersensitivity . We evaluated 18 women with recurrent vulvovaginal candidiasis that was unresponsive to all other modalities of therapy and who were skin-test positive to Candida albicans with a positive prick test or intradermal skin test . Three patients had late-phase skin test reactions only . Of the 18 study participants, 16 responded with significant improvement in the mean incidence of episodes of vaginitis per year from 17.2 +/- 2.0 to 4.3 +/- 1.8 (p less than 0.0004) . Overall, there was approximately 79% improvement in these patients . More than half the women were also atopic but were not first seen with these allergic symptoms . These data suggest that certain women who have chronic vaginal candidiasis may have a local hypersensitivity response to Candida that may improve with allergy immunotherapy with C . albicans extract . A double-blind, placebo-controlled trial in a homogeneous group of women with standardized extract is needed to establish this as a recommended form of therapy in this subgroup of patients.

Antimicrob Agents Chemother, 1990 Feb, 34(2), 196 - 201
Effects of antifungal agents on the function of human neutrophils in vitro; Roilides E et al.; Polymorphonuclear leukocytes (PMNs) are an important component of the host defense against fungi . We investigated the influence of five antifungal agents on PMN function and compared them with amphotericin B (AmB) . The in vitro effects of AmB, flucytosine, ketoconazole, fluconazole, Sch-39304, and cilofungin (LY121019) on chemotaxis, phagocytosis, oxidative metabolism of PMN as reflected by superoxide anion (O2-) generation, and intracellular killing of Candida albicans blastoconidia were examined . With regard to chemotaxis in response to N-formylmethionyl-leucyl-phenylalanine, as measured by the multiwell chamber method, AmB induced a marked decrease (greater than or equal to 5 micrograms/ml), whereas ketoconazole at 5 micrograms/ml enhance it . Phagocytosis was significantly decreased after pretreatment of PMNs with AmB and Sch-39304 (greater than 5 and 1 to 10 micrograms/ml, respectively) . O2- production after stimulation of PMNs with N-formylmethionyl-leucyl-phenyl-alanine was significantly decreased by AmB (greater than 5 micrograms/ml) and enhanced by Sch-39304 (1 to 5 micrograms/ml) . In contrast, intracellular killing, as tested by methylene blue staining, was enhanced by ketoconazole (5 micrograms/ml) and Sch-39304 (1 to 5 micrograms/ml) . Flucytosine, fluconazole, and cilofungin did not affect PMN function at therapeutic concentrations . The results of this comprehensive study indicate that AmB, flucytosine, cilofungin, and the newer azoles, at safely achievable concentrations, generally do not suppress PMN function at therapeutic enhance selective functions.

Mol Microbiol, 1990 Feb, 4(2), 197 - 207
Isolation of a chitin synthase gene (CHS1) from Candida albicans by expression in Saccharomyces cerevisiae; Au-Young J et al.; Chitin synthase activity was studied in yeast and hyphal forms of Candida albicans . pH-activity profiles showed that yeast and hyphae contain a protease-dependent activity that has an optimum at pH 6.8 . In addition, there is an activity that is not activated by proteolysis in vitro and which shows a peak at pH 8.0 . This suggests there are two distinct chitin synthases in C . albicans . A gene for chitin synthase from C . albicans (CHS1) was cloned by heterologous expression in a Saccharomyces cerevisiae chs1 mutant . Proof that the cloned chitin synthase is a C . albicans membrane-bound zymogen capable of chitin biosynthesis in vitro was based on several criteria . (i) the CHS1 gene complemented the S . cerevisiae chs1 mutation and encoded enzymatic activity which was stimulated by partial proteolysis; (ii) the enzyme catalyses incorporation of {14C}-GlcNAc from the substrate, UDP{U-14C}-GlcNAc, into alkali-insoluble chitin; (iii) Southern analysis showed hybridization of a C . albicans CHS1 probe only with C . albicans DNA and not with S . cerevisiae DNA; (iv) pH profiles of the cloned enzyme showed an optimum at pH 6.8 . This overlaps with the pH-activity profiles for chitin synthase measured in yeast and hyphal forms of C . albicans . Thus, CHS1 encodes only part of the chitin synthase activity in C . albicans . A gene for a second chitin synthase in C . albicans with a pH optimum at 8.0 is proposed . DNA sequencing revealed an open reading frame of 2328 nucleotides which predicts a polypeptide of Mr 88,281 with 776 amino acids . The alignment of derived amino acid sequences revealed that the CHS1 gene from C . albicans (canCHS1) is homologous (37% amino acid identity) to the CHS1 gene from S . cerevisiae (sacCHS1).

Infect Immun, 1990 Feb, 58(2), 309 - 14
Purification and characterization of the extracellular C3d-binding protein of Candida albicans; Saxena A et al.; A C3d-binding glycoprotein was purified from the culture filtrate of Candida albicans by preparative isoelectric focusing . The protein possessed a pI of 3.9 to 4.1 and could inhibit rosetting of EAC3d (sheep erythrocytes conjugated to C3d) by pseudohyphae of C . albicans . When analyzed by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and mercaptoethanol, the protein migrated as a doublet with apparent molecular masses of 55 and 60 kilodaltons (kDa) and as a 50-kDa band in nonreducing gels . These results were observed with Aurodye stain for proteins . Western immunoblot, and concanavalin A stain, which indicates that both bands contain carbohydrate as well as antigenic determinants . The treatment of purified glycoprotein with endoglycosidase F but not endoglycosidases H, N, and O resulted in a complete conversion of the doublet into a faster-migrating broad band with an apparent molecular mass of 45 kDa . When the amino acid analysis of the C3d-binding protein was compared with that of the CR2 from B lymphocytes, significant differences were observed . These data indicate that C . albicans secretes a C3d-binding protein during growth in vitro which appears to be different from the mammalian C3d receptor.

J Clin Pathol, 1990 Feb, 43(2), 114 - 8
Cerebral aspergillosis in liver transplantation; Boon AP et al.; Nine cases of cerebral aspergillosis were identified in a series of 44 brains obtained at necropsy from patients who had undergone liver transplantation . In two of these there was dual infection with Candida albicans . The primary focus of infection was invariably in the lungs . One case of pulmonary Aspergillus infection was found with no evidence of cerebral disease . Infection tended to occur in the period soon after transplantation, was associated with high dose steroids, retransplantation, and showed a significant seasonal incidence . Neurological findings were non-specific and only two cases were diagnosed before death . Aspergillus infection soon after transplantation indicates that this organism is a considerable nosocomial hazard, particularly in the winter and spring months . Positive cultures before death are rarely obtained and antifungal treatment should be started on clinical suspicion alone.

Enferm Infecc Microbiol Clin, 1990 Feb, 8(2), 91 - 3
{In vitro sensitivity to 5-fluorocytosine and amphotericin B of yeasts of the Candida genus isolated in Barcelona}; Torres-Rodriguez JM et al.; In 200 strains of Candida sp, 38.5% were found to have intermediate sensitivity or to be resistant to amphotericin B and/or 5-fluorocytosine by the agar diffusion method . When the minimal inhibitory concentrations of these strains were measured, only 7.8% were resistant to amphotericin B and 2.8% to 5-fluorocytosine . The species with the highest levels of resistance were C . parapsilosis, C . tropicalis and Torulopsis glabrata . Candida albicans did not show resistance to 5-fluorocytosine.

Acta Odontol Scand, 1990 Feb, 48(1), 27 - 36
Laboratory identification and sensitivity testing of yeast isolates; Sandven P; Methods used for identification and sensitivity testing of yeasts are presented . Identification depends on both morphologic features and biochemical characteristics . The germ tube test is a simple test for the identification of the commonest yeast pathogen, Candida albicans . Species not identified by this method can be identified by means of several other tests, the most important being the carbohydrate assimilation test . Several kits are commercially available and most appear to be satisfactory . Antifungal susceptibility tests are not standardized, and results are often subject to considerable variation . Until improved methods are developed, it might be advisable that smaller laboratories only do a preliminary screening test for flucytosine susceptibility and, if indicated, also for amphotericin B susceptibility . Important isolates should be sent to laboratories with a special interest in antifungal susceptibility testing for more extensive testing.

Biochim Biophys Acta, 1990 Jan 15, 1021(1), 39 - 45
Affinity of amphotericin B for phosphatidylcholine vesicles as a determinant of the in vitro cellular toxicity of liposomal preparations; Jullien S et al.; Candida albicans and human erythrocytes were treated with liposomal amphotericin B (AmB) obtained by incubation of free AmB with small unilamellar vesicles (SUV) composed of unsaturated fatty acyl chains phosphatidylcholine (egg-yolk PC) . Cellular effects were determined by changes in the K+ internal content of cells and in the number of colonies formed by fungal cells or as hemolysis, measured as a decrease in haemoglobin retention by erythrocytes . Dose-response curves were obtained by two procedures: either the ratio of AmB to phospholipids was kept constant over the AmB concentration range used (R = 10(-2} or the phospholipid concentration was kept constant (C = 0.2 mM) and the concentration of AmB varied . The liposomal preparations of AmB were as active against fungi as AmB in dimethylsulfoxide but less active (internal K+ changes) or inactive (hemolysis) against erythrocytes . On the other hand the binding of AmB to the SUV, as a function of the AmB concentration, was monitored by circular dichroism, fluorescence and UV absorption, in the two conditions used for the cellular studies . The amount of AmB bound when the total concentration of antibiotic was 2.10(-7) M was very low but increased with concentration and reached 90% at 10(-5) M . In all the assays we used, the anticellular effects could be attributed to the levels of AmB remaining free (unbound to the lipids) . The variations of these levels with total AmB concentration could therefore explain the increased selectivity of liposomal AmB in toxicity against fungi and erythrocytes as compared to that of AmB added as a solution in dimethylsulfoxide . Indeed fungal cells are sensitive to low concentrations of AmB in dimethylsulfoxide; at these concentrations, in liposomal preparations, AmB is not bound to phospholipids and therefore as active as if added in dimethylsulfoxide . By contrast erythrocytes are only sensitive to much higher concentrations of AmB in dimethylsulfoxide; at these concentrations AmB is almost totally bound to phospholipids and therefore much less active.

J Immunol, 1990 Jan 15, 144(2), 707 - 16
Different effects of native Candida albicans mannan and mannan-derived oligosaccharides on antigen-stimulated lymphoproliferation in vitro; Podzorski RP et al.; Yeast cell wall mannan polysaccharide has been proposed to contribute to immune dysfunction associated with chronic infections involving Candida albicans . This influence of mannan has been suggested based partially upon studies of the in vitro immunoinhibitory effects of mannans prepared from Saccharomyces cerevisiae or C . albicans by precipitation with Fehling's reagent, which provides a structurally modified product contaminated with copper . We have therefore evaluated the immunoinhibitory influence of a more native C . albicans mannan prepared by complexation with cetyltrimethylammonium bromide (CTAB) . CTAB mannan was a potent stimulator of lymphoproliferation when added to human PMBC from donors responsive to Candida; it has no inhibitory influence on lympho-proliferation induced by Candida or other Ag . In contrast, members of a family of mannose oligosaccharides (disaccharide through hexasaccharide) derived from the CTAB mannan by weak alkaline degradation did not stimulate lymphoproliferation, but were potent inhibitors of lymphoproliferation stimulated by Candida and other Ag . Fifty percent inhibitory doses were 260 to 34 microM, respectively . Compositional analyses of these immunoinhibitory oligomers showed them to be composed of mannose and free of contaminating protein . We propose that mannan-derived oligosaccharides produced by catabolism of mannan in vivo are immunoinhibitory and contribute to the deficit in cell-mediated immune function associated with chronic candidiasis.

Pathol Biol (Paris), 1990 Jan, 38(1), 13 - 8
{Effect of treatment with clindamycin, erythromycin, rifamycin or gentamicin on the ingestion capacity of peritoneal macrophages in mice}; Amurrio C et al.; The effect of treatment with clindamycin, erythromycin, rifamycin and gentamicin on the ingestion capacity of the mouse peritoneal macrophage was studied . Female six-eight week old OF1 mice were treated with minimum and maximum doses clinically used for the different antibiotics (15 and 40 mg/kg/day of clindamycin, 15 and 57.5 mg/kg/day of erythromycin, 10 and 30 mg/kg/day of rifamycin, 3 and 6 mg/kg/day of gentamicin) . Two treatment periods of 72 hours and one week were assayed for each antibiotic-dose combination . Antibiotic was administered twice daily, every twelve hours . Twelve hours after the last dose was given, macrophages were obtained through peritoneal lavage and a kinetic study of Candida albicans blastospore ingestion was made . One week treatment with 15 mg/kg/day and 72 hours treatment with 57.5 mg/kg/day of erythromycin produced a significant ingestion enhancement whereas one week treatment with 57.5 mg/kg/day of erythromycin and all treatments with gentamicin gave rise to an ingestion depression . 72 hours treatment with 15 and 40 mg/kg/day and one week treatment with 15 mg/kg/day of clindamycin, 15 mg/kg/day of erythromycin and 10 and 30 mg/kg/day of rifamycin did not modify macrophage ingestion capacity . One week treatment with 40 mg/kg/day of clindamycin and 10 and 30 mg/kg/day of rifamycin gave rise to an acceleration of the ingestion process.

J Bacteriol, 1990 Jan, 172(1), 224 - 35
Ultrastructure and antigenicity of the unique cell wall pimple of the Candida opaque phenotype; Anderson J et al.; Cells of Candida albicans WO-1 switch frequently and reversibly between two colony-forming phenotypes, white and opaque . In the white form, budding cells appear similar to those of most other strains of C . albicans, but in the opaque form, budding cells are larger, are bean shaped, and possess pimples on the wall . These pimples exhibit a unique and complex morphology . With scanning electron microscopy, a central pit can be discerned, and in many cases, a bleb can be observed emerging from the pimple center . With transmission electron microscopy, channels are evident in some pimples and vesicles are apparent under the pimple in the cytoplasm, in the actual wall of the pimple, or emerging from the tip of the pimple . A large vacuole predominates in the opaque-cell cytoplasm . This vacuole is usually filled with spaghettilike membranous material and in a minority of cases is filled with vesicles, many of which exhibit a relatively uniform size . An antiserum to opaque cells recognizes three opaque-cell-specific antigens with molecular masses of approximately 14.5, 21, and 31 kilodaltons (kDa) . Absorption with nonpermeabilized opaque cells demonstrated that only the 14.5-kDa antigen is on the cell surface; indirect immunogold labeling demonstrated that it is localized in or on the pimple . The possibility is suggested that the vacuole of opaque cells is the origin of membrane-bound vesicles which traverse the wall through specialized pimple structures and emerge from the pimple with an intact outer double membrane, a unique phenomenon in yeast cells . The opaque-cell-specific 14.5-kDa antigen either is in the pimple channel or is a component of the emerging vesicle . The functions of the unique opaque-cell pimple and emerging vesicle are not known.

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